MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Advances in Cancer Research' source. Mon, 21 Nov 2011 21:13:57 +0100 http://www.medworm.com/index.php?rid=5248108&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925299%26dopt%3DAbstract Authors: Gisselsson D Abstract Clonal evolution in cancer is intimately linked to the concept of intratumor cellular diversity, as the latter is a prerequisite for Darwinian selection at the micro-level. It has been frequently suggested in the literature that clonal evolution can be promoted by an elevated rate of mutation in tumor cells, so-called genomic instability, the mechanisms of which are now becoming increasingly well characterized. However, several issues need clarification before the presumably complex relationship between mutation rate, intratumor diversity, and clonal evolution can be understood sufficiently well to translate into models that predict the course of tumor disease. In particular, it has to be clarified which of the proposed mechanisms for genomic instabil... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=5248108 Sat, 24 Sep 2011 05:46:40 +0100 5248108 http://www.medworm.com/index.php?rid=5248107&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925300%26dopt%3DAbstract Authors: Genescà A, Pampalona J, Frías C, Domínguez D, Tusell L Abstract Most solid tumors are unable to maintain the stability of their genomes at the chromosome level. Indeed, cancer cells display highly rearranged karyotypes containing translocations, amplifications, deletions, and gains and losses of whole chromosomes, which reshuffle steadily. This chromosomal instability most likely occurs early in the development of cancer, and may represent an important step in promoting the multiple genetic changes required for the initiation and/or progression of the disease. Different mechanisms may underlie chromosome instability in cancer cells, but a prominent role for telomeres, the tip of linear chromosomes, has been determined. Telomeres are ribonucleoprotein structures that pre... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=5248107 Sat, 24 Sep 2011 05:46:40 +0100 5248107 http://www.medworm.com/index.php?rid=5248106&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925301%26dopt%3DAbstract Authors: Nicholson JM, Cimini D Abstract Aneuploidy is a common feature of cancer cells, and is believed to play a critical role in tumorigenesis and cancer progression. Most cancer cells also exhibit high rates of mitotic chromosome mis-segregation, a phenomenon known as chromosomal instability, which leads to high variability of the karyotype. Here, we describe the nature, nuances, and implications of cancer karyotypic diversity. Moreover, we summarize recent studies aimed at identifying the mitotic defects that may be responsible for inducing chromosome mis-segregation in cancer cells. These include kinetochore attachment errors, spindle assembly checkpoint dysfunction, mitotic spindle defects, and other cell division inaccuracies. Finally, we discuss how such mitotic errors gen... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=5248106 Sat, 24 Sep 2011 05:46:40 +0100 5248106 http://www.medworm.com/index.php?rid=5248105&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925302%26dopt%3DAbstract Authors: Gadji M, Vallente R, Klewes L, Righolt C, Wark L, Kongruttanachok N, Knecht H, Mai S Abstract This chapter focuses on the three-dimensional organization of the nucleus in normal, early genomically unstable, and tumor cells. A cause-consequence relationship is discussed between nuclear alterations and the resulting genomic rearrangements. Examples are presented from studies on conditional Myc deregulation, experimental tumorigenesis in mouse plasmacytoma, nuclear remodeling in Hodgkin's lymphoma, and in adult glioblastoma. A model of nuclear remodeling is proposed for cancer progression in multiple myeloma. Current models of nuclear remodeling are described, including our model of altered nuclear architecture and the onset of genomic instability. PMID: 21925302 [PubMed ... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=5248105 Sat, 24 Sep 2011 05:46:40 +0100 5248105 http://www.medworm.com/index.php?rid=5248104&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925303%26dopt%3DAbstract Authors: Teixeira MR, Heim S Abstract All or almost all neoplasias subjected to systematic cytogenetic scrutiny have been found to harbor acquired chromosomal aberrations. The paradigm stemming from the study of hematopoietic malignancies and sarcomas is that cancers are of monoclonal origin (i.e., they have developed from a single transformed somatic progenitor) because all the neoplastic parenchyma cells share at least one primary chromosomal abnormality, with subsequent clonal evolution along the lines of Darwinian selection occurring among the various subclones carrying secondary aberrations. When carcinomas began to be studied more extensively by cytogenetic methods, however, sometimes many cytogenetically unrelated clones were found, in seeming contradiction to the monoclonal... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=5248104 Sat, 24 Sep 2011 05:46:40 +0100 5248104 http://www.medworm.com/index.php?rid=5248103&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925304%26dopt%3DAbstract We describe how these techniques can be used to resolve tumor ploidy, normal cell admixture, and subclonality. We also exemplify how genotyping techniques can be applied in tumor studies to elucidate the hierarchy among tumor clones, and thus, provide means to study clonal expansion and tumor evolution. PMID: 21925304 [PubMed - in process] (Source: Advances in Cancer Research) Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=5248103 Sat, 24 Sep 2011 05:46:40 +0100 5248103 http://www.medworm.com/index.php?rid=5248102&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925305%26dopt%3DAbstract Authors: Squire JA, Park PC, Yoshimoto M, Alami J, Williams JL, Evans A, Joshua AM Abstract This chapter will summarize novel understandings of the early molecular events in prostatic carcinogenesis that may underlie both the genetic and clinical heterogeneity. Areas covered include preneoplasia, stem cell concepts, telomere abnormalities, and the nature of tumor-stromal interactions. The oncogenomics of prostate cancer is reviewed with emphasis on androgen signaling, ETS gene family aberrations, and PTEN deletion. The notion that "field cancerization," coupled with genomic instability may explain both the occurrence of multifocal disease, and the recent observations of genetic diversity of ERG alteration in individual tumors are discussed. Collectively, genomic studies are rapidly... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=5248102 Sat, 24 Sep 2011 05:46:40 +0100 5248102 http://www.medworm.com/index.php?rid=5248101&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925306%26dopt%3DAbstract Authors: Heng HH, Stevens JB, Bremer SW, Liu G, Abdallah BY, Ye CJ Abstract The recently introduced genome theory of cancer evolution provides a new framework for evolutionary studies on cancer. In particular, the established relationship between the large number of individual molecular mechanisms and the general evolutionary mechanism of cancer calls upon a change in our strategies that have been based on the characterization of common cancer gene mutations and their defined pathways. To further explain the significance of the genome theory of cancer evolution, a brief review will be presented describing the various attempts to illustrate the evolutionary mechanism of cancer, followed by further analysis of some key components of somatic cell evolution, including the diversity of ... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=5248101 Sat, 24 Sep 2011 05:46:40 +0100 5248101 http://www.medworm.com/index.php?rid=5248100&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925307%26dopt%3DAbstract Authors: Pietras A Abstract Cancer cells within a given tumor were long regarded as a largely homogeneous group of cells originating from a common progenitor cell. However, it is increasingly appreciated that there is a considerable heterogeneity within tumors also on the tumor cell level. This heterogeneity extends to virtually all measurable properties of cancer cells, ranging from differentiation state, proliferation rate, migratory and invasive capacity to size, and therapeutic response. Such heterogeneity likely represents a major therapeutic hurdle, but the mechanisms underlying its emergence remain poorly understood and a controversial topic. The cancer stem cell model of tumor progression has gained increasing support during the past several years. In this review, I will di... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=5248100 Sat, 24 Sep 2011 05:46:40 +0100 5248100 http://www.medworm.com/index.php?rid=5248099&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21925308%26dopt%3DAbstract Authors: Vincent MD Abstract A good account of the nature of cancer should provide not only a description of its consistent features, but also how they arise, how they are maintained, why conventional chemotherapy succeeds, and fails, and where to look for better targets. Cancer was once regarded as enigmatic and inexplicable; more recently, the "mutation theory," based on random alterations in a relatively small set of proto-oncogenes and tumor suppressor genes, has enjoyed widespread acceptance. The "mutation theory," however, is noticeable for its failure to explain the basis of differential chemosensitivity, for providing a paucity of targets, especially druggable ones, and for justifying the development of targeted therapies with, in general, disappointingly abbreviated clinic... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=5248099 Sat, 24 Sep 2011 05:46:40 +0100 5248099 http://www.medworm.com/index.php?rid=5062003&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21704226%26dopt%3DAbstract Authors: Lauth M, Toftgård R Numerous signaling pathways are misregulated in pancreatic ductal adenocarcinoma (PDAC), a highly malignant type of cancer. One of these is the Hedgehog (HH) pathway, which is normally involved in patterning processes in the developing embryo. Expression of the main ligand Sonic Hedgehog is an early event in carcinogenesis and correlates with the mutation of the KRAS oncogene, the cardinal molecular feature of pancreatic cancer. Recent data establish a functional role for HH signaling primarily in the tumor microenvironment, where it is involved in myofibroblast differentiation and the induction of stroma-derived growth promoting molecules. Given the protumorigenic functions of the abundant stromal desmoplasia typically associated with pancreatic cancer, t... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=5062003 Mon, 25 Jul 2011 22:30:02 +0100 5062003 http://www.medworm.com/index.php?rid=5062002&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21704227%26dopt%3DAbstract Authors: Lemaire M, Deleu S, De Bruyne E, Van Valckenborgh E, Menu E, Vanderkerken K Multiple myeloma (MM) is a deadly plasma cell cancer that resides in the bone marrow (BM). Numerous studies have demonstrated the involvement of the BM microenvironment supporting tumor growth, angiogenesis, bone disease and drug resistance. Reciprocal interactions between the different components of the BM microenvironment and the MM cells are necessary to regulate migration, differentiation, proliferation and survival of the malignant plasma cells. In this review we focus on the interactions and molecular mechanisms by which the BM microenvironment exert these effects. Better understanding of these interactions and the study of the epigenetic changes that tumor cells undergo are necessary in order to... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=5062002 Mon, 25 Jul 2011 22:30:02 +0100 5062002 http://www.medworm.com/index.php?rid=5062000&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21704228%26dopt%3DAbstract Authors: Yang J, Corces VG Chromatin insulators are DNA-protein complexes with broad functions in nuclear biology. Based on the ability of insulator proteins to interact with each other, it was originally found that insulators form loops that bring together distant regions of the genome. Data from genome-wide localization studies indicate that insulator proteins can be present in intergenic regions as well as at the 5', introns or 3' of genes, suggesting a variety of roles for insulator loops in chromosome biology. Recent results suggest that insulators mediate intra- and interchromosomal interactions to affect transcription, imprinting, and recombination. Cells have developed mechanisms to control insulator activity by recruiting specialized proteins or by covalent modification of cor... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=5062000 Mon, 25 Jul 2011 22:30:02 +0100 5062000 http://www.medworm.com/index.php?rid=5061999&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21704229%26dopt%3DAbstract We describe what is known about how Myc is destroyed by ubiquitin (Ub)-mediated proteolysis, attempt to rationalize the role of different Ub-protein ligases and deubiquitylating enzymes (dUbs) in the regulation of Myc stability, and detail how these processes go awry in cancer. Finally, we discuss how our understanding of Myc regulation by the ubiquitin-proteasome system (UPS) can expose strategies for therapeutic intervention in human malignancies. PMID: 21704229 [PubMed - in process] (Source: Advances in Cancer Research) Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=5061999 Mon, 25 Jul 2011 22:30:02 +0100 5061999 http://www.medworm.com/index.php?rid=5061998&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21704230%26dopt%3DAbstract Authors: Soussi T TP53 mutations are the most frequent genetic alterations found in human cancer. For more than 20years, TP53 mutation databases have collected over 30,000 somatic mutations from various types of cancer. Analyses of these mutations have led to many types of studies and have improved our knowledge about the TP53 protein and its function. The recent advances in sequencing methodologies and the various cancer genome sequencing projects will lead to a profound shift in database curation and data management. In this paper, we will review the current status of the TP53 mutation database, its application to various fields of research, and how data quality and curation can be improved. We will also discuss how the genetic data will be stored and handled in the future and the co... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=5061998 Mon, 25 Jul 2011 22:30:02 +0100 5061998 http://www.medworm.com/index.php?rid=5061997&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21704829%26dopt%3DAbstract Authors: Lladser A, Sanhueza C, Kiessling R, Quest AF Survivin, the smallest member of the inhibitors of apoptosis proteins (IAPs), plays an important role in the control of apoptosis, cell division, and cell migration/metastasis. Survivin is expressed and required for normal fetal development but is then generally no longer present in most adult tissues. However, reexpression of survivin is observed in numerous human cancers where presence of the protein is associated with enhanced proliferation, metastasis, poor prognosis, and decreased patient survival. Given the relatively selective expression in cancer cells, but not in normal tissue (tumor-associated antigen), and its importance in tumor cell biology, survivin has emerged as an attractive target for cancer treatment. Here, we dis... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=5061997 Mon, 25 Jul 2011 22:30:02 +0100 5061997 http://www.medworm.com/index.php?rid=5061996&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21704830%26dopt%3DAbstract Authors: Kelly GL, Strasser A The link between evasion of apoptosis and the development of cellular hyperplasia and ultimately cancer is implicitly clear if one considers how many cells are produced each day and, hence, how many cells must die to make room for the new ones (reviewed in Raff, 1996). Furthermore, cells are frequently experiencing noxious stimuli that can cause lesions in their DNA and faults in DNA replication can occur during cellular proliferation. Such DNA damage needs to be repaired efficiently or cells with irreparable damage must be killed to prevent subsequent division of aberrant cells that may fuel tumorigenesis (reviewed in Weinberg, 2007). The detection of genetic lesions in human cancers that activate prosurvival genes or disable proapoptotic genes have provi... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=5061996 Mon, 25 Jul 2011 22:30:02 +0100 5061996 http://www.medworm.com/index.php?rid=5061995&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21704831%26dopt%3DAbstract Authors: Tervonen TA, Partanen JI, Saarikoski ST, Myllynen M, Marques E, Paasonen K, Moilanen A, Wohlfahrt G, Kovanen PE, Klefstrom J Epithelial architecture is formed in tissues and organs when groups of epithelial cells are organized into polarized structures. The epithelial function and integrity as well as signaling across the epithelial layer is orchestrated by apical junctional complexes (AJCs), which are landmarks for PAR/CRUMBS and lateral SCRIB polarity modules and by dynamic interactions of the cells with underlying basement membrane (BM). These highly organized epithelial architectures are demolished in cancer. In all advanced epithelial cancers, malignant cells have lost polarity and connections to the basement membrane and they have become proliferative, motile, and invasi... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=5061995 Mon, 25 Jul 2011 22:30:02 +0100 5061995 http://www.medworm.com/index.php?rid=5061983&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21704832%26dopt%3DAbstract Authors: Bangham CR, Toulza F Human T-lymphotropic virus type 1 (HTLV-1) causes adult T-cell leukaemia/lymphoma (ATLL) in ∼5% of HTLV-1-infected people. ATLL cells frequently express several molecules that are characteristic of regulatory T cells (Tregs), notably CD4, CD25 and the transcription factor FoxP3. It has therefore recently been suggested that HTLV-1 selectively infects and transforms Tregs. We show that HTLV-1 induces and maintains a high frequency of FoxP3+ T cells by inducing expression of the chemokine CCL22; the frequency is especially high in patients with chronic ATLL. In turn, the FoxP3+ T cells exert both potentially beneficial and harmful effects: they suppress the growth of autologous ATLL clones and may also suppress the host's cytotoxic T lymphocyte response, w... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=5061983 Mon, 25 Jul 2011 22:30:02 +0100 5061983 http://www.medworm.com/index.php?rid=4171595&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21070913%26dopt%3DAbstract Authors: Knudsen BS, Vasioukhin V Prostate cancer is a major health problem as it continues to be the most frequently diagnosed cancer in men in the Western world. While improved early detection significantly decreased mortality, prostate cancer still remains the second leading cause of cancer-related death in Western men. Understanding the mechanisms of prostate cancer initiation and progression should have a significant impact on development of novel therapeutic approaches that can help to combat this disease. The recent explosion of novel high-throughput genetic technologies together with studies in animal models and human tissues allowed a comprehensive analysis and functional validation of the molecular changes. This chapter will summarize and discuss recently identified critical ... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=4171595 Tue, 16 Nov 2010 21:20:03 +0100 4171595 http://www.medworm.com/index.php?rid=4171594&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21070914%26dopt%3DAbstract Authors: Yokota J, Shiraishi K, Kohno T Lung cancer is the leading cause of cancer death worldwide, and cigarette smoking is the major environmental factor for its development. To elucidate the genetic differences in the susceptibility to lung cancer among individuals, genetic factors involved in tobacco-induced lung cancers have been extensively investigated and a number of genetic polymorphisms have been identified to date as candidates. Most of the polymorphisms identified are of genes encoding proteins associated with the activity to metabolize tobacco smoke carcinogens and to suppress mutations induced by those carcinogens, and functional significances have been elucidated for some of these polymorphisms. However, the significance of these polymorphisms in the contribution to lung... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=4171594 Tue, 16 Nov 2010 21:20:03 +0100 4171594 http://www.medworm.com/index.php?rid=4171593&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21070915%26dopt%3DAbstract Authors: Campoli M, Ferrone S, Wang X The lack of effective conventional therapies for the treatment of advanced stage melanoma has stimulated interest in the development of novel strategies for the management of patients with malignant melanoma. Among them, immunotherapy has attracted much attention because of the potential role played by immunological events in the clinical course of melanoma. For many years, T cell-based immunotherapy has been emphasized in part because of the disappointing results of the monoclonal antibody (mAb)-based clinical trials conducted in the early 1980s and in part because of the postulated major role played by T cells in tumor growth control. More recently, mAb-based therapies have gained in popularity given their clinical and commercial success for a va... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=4171593 Tue, 16 Nov 2010 21:20:03 +0100 4171593 http://www.medworm.com/index.php?rid=4171592&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21070916%26dopt%3DAbstract Authors: Velho S, Corso G, Oliveíra C, Seruca R Microsatellite instability (MSI) occurs in about 15% of gastrointestinal cancers and it is associated with specific clinic, pathologic, and molecular features of the tumors. MSI-high (MSI-H) carcinomas also follow specific tumor development pathways. This review is focused on the molecular profile of alterations in members of the KRAS signaling pathway (EGFR, KRAS, BRAF, PIK3CA, RASSF1A, and MLK3 genes) in MSI gastrointestinal carcinomas. Alterations in these genes characterize more than half of gastrointestinal cancers and frequently occur simultaneously in the same tumor, pinpointing the KRAS signaling pathway as one of the most frequently altered pathways in this subset of cancers. Nowadays, many and novel inhibitors targeting molecul... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=4171592 Tue, 16 Nov 2010 21:20:03 +0100 4171592 http://www.medworm.com/index.php?rid=4140433&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21034964%26dopt%3DAbstract We present a model for the evolution of EBV-induced lymphomas in which tumors are initially "addicted" to the virus for almost all oncogenic functions. These tumors are targets for the immune system because they express multiple immunogenic viral proteins. Therefore, EBV-induced tumors are under selective pressure to acquire cellular mutations that can replace viral functions. We posit that the heterogeneity in viral gene expression among different EBV-associated lymphomas reflects a dynamic process by which tumors evolve to be less dependent on the virus. PMID: 21034964 [PubMed - in process] (Source: Advances in Cancer Research) Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=4140433 Sun, 07 Nov 2010 13:10:03 +0100 4140433 http://www.medworm.com/index.php?rid=4140432&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21034965%26dopt%3DAbstract Authors: Kao JH, Chen PJ, Chen DS Hepatocellular carcinoma (HCC) is one of the commonest cancers worldwide, and more than half of HCC patients are attributable to persistent hepatitis B virus (HBV) infections. The best and cheapest way to prevent HBV-related HCC is the implementation of universal hepatitis B vaccination program, by which the incidence rates of childhood HCC have been reduced in several countries, including Taiwan. However, there are still hundreds of millions of HBV carriers in the world that remain a global health challenge. In the past decade, several hepatitis B viral factors such as serum HBV DNA level, genotype, and naturally occurring mutants have already been identified to influence liver disease progression and HCC development in HBV carriers. Several easy-to-u... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=4140432 Sun, 07 Nov 2010 13:10:03 +0100 4140432 http://www.medworm.com/index.php?rid=4140431&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21034966%26dopt%3DAbstract Authors: Smith J, Mun Tho L, Xu N, A Gillespie D DNA damage is a key factor both in the evolution and treatment of cancer. Genomic instability is a common feature of cancer cells, fuelling accumulation of oncogenic mutations, while radiation and diverse genotoxic agents remain important, if imperfect, therapeutic modalities. Cellular responses to DNA damage are coordinated primarily by two distinct kinase signaling cascades, the ATM-Chk2 and ATR-Chk1 pathways, which are activated by DNA double-strand breaks (DSBs) and single-stranded DNA respectively. Historically, these pathways were thought to act in parallel with overlapping functions; however, more recently it has become apparent that their relationship is more complex. In response to DSBs, ATM is required both for ATR-Chk1 activat... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=4140431 Sun, 07 Nov 2010 13:10:03 +0100 4140431 http://www.medworm.com/index.php?rid=4140430&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21034967%26dopt%3DAbstract Authors: Angelica Cortez M, Ivan C, Zhou P, Wu X, Ivan M, Adrian Calin G microRNAs (miRNAs) are master regulators of gene expression. By degrading or blocking translation of messenger RNA targets, these noncoding RNAs can regulate the expression of more than half of all protein-coding genes in mammalian genomes. Aberrant miRNA expression is well characterized in cancer progression and has prognostic implications for cancer in general. Over the past several years, accumulating evidence has demonstrated that genomic alterations in miRNA genes are correlated with all aspects of cancer biology. In this review, we describe the effects of miRNA deregulation in the cellular pathways that lead to the progressive conversion of normal cells into cancer cells as well as in cancer diagnosis and th... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=4140430 Sun, 07 Nov 2010 13:10:03 +0100 4140430 http://www.medworm.com/index.php?rid=3486798&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20399955%26dopt%3DAbstract Authors: Gjoerup O, Chang Y Over 50 years of polyomavirus research has produced a wealth of insights into not only general biologic processes in mammalian cells, but also, how conditions can be altered and signaling systems tweaked to produce transformation phenotypes. In the past few years three new members (KIV, WUV, and MCV) have joined two previously known (JCV and BKV) human polyomaviruses. In this review, we present updated information on general virologic features of these polyomaviruses in their natural host, concentrating on the association of MCV with human Merkel cell carcinoma. We further present a discussion on advances made in SV40 as the prototypic model, which has and will continue to inform our understanding about viruses and cancer. PMID: 20399955 [PubMed - in pro... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=3486798 Tue, 20 Apr 2010 18:24:03 +0100 3486798 http://www.medworm.com/index.php?rid=3486797&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20399956%26dopt%3DAbstract Authors: Grossmann KS, Rosário M, Birchmeier C, Birchmeier W Deregulation of signaling pathways, through mutation or other molecular changes, can ultimately result in disease. The tyrosine phosphatase Shp2 has emerged as a major regulator of receptor tyrosine kinase (RTK) and cytokine receptor signaling. In the last decade, germline mutations in the human PTPN11 gene, encoding Shp2, were linked to Noonan (NS) and LEOPARD syndromes, two multisymptomatic developmental disorders that are characterized by short stature, craniofacial defects, cardiac defects, and mental retardation. Somatic Shp2 mutations are also associated with several types of human malignancies, such as the most common juvenile leukemia, juvenile myelomonocytic leukemia (JMML). Whereas NS and JMML are caused by gai... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=3486797 Tue, 20 Apr 2010 18:24:03 +0100 3486797 http://www.medworm.com/index.php?rid=3486779&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20399957%26dopt%3DAbstract Authors: Keeley EC, Mehrad B, Strieter RM The tumor microenvironment is extremely complex that depends on tumor cell interaction with the responding host cells. Angiogenesis, or new blood vessel growth from preexisting vasculature, is a preeminent feature of successful tumor growth of all solid tumors. While a number of factors produced by both the tumor cells and host responding cells have been discovered that regulate angiogenesis, increasing evidence is growing to support the important role of CXC chemokines in this process. As a family of cytokines, the CXC chemokines are pleiotropic in their ability to regulate tumor-associated angiogenesis, as well as cancer cell metastases. In this chapter, we will discuss the disparate activity that CXC chemokines play in regulating cancer-asso... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=3486779 Tue, 20 Apr 2010 18:24:03 +0100 3486779 http://www.medworm.com/index.php?rid=3486777&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20399958%26dopt%3DAbstract Authors: Walrath JC, Hawes JJ, Van Dyke T, Reilly KM Mouse models of human cancer have played a vital role in understanding tumorigenesis and answering experimental questions that other systems cannot address. Advances continue to be made that allow better understanding of the mechanisms of tumor development, and therefore the identification of better therapeutic and diagnostic strategies. We review major advances that have been made in modeling cancer in the mouse and specific areas of research that have been explored with mouse models. For example, although there are differences between mice and humans, new models are able to more accurately model sporadic human cancers by specifically controlling timing and location of mutations, even within single cells. As hypotheses are developed... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=3486777 Tue, 20 Apr 2010 18:24:03 +0100 3486777 http://www.medworm.com/index.php?rid=3486776&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20399959%26dopt%3DAbstract Authors: Sharabi A, Ghera NH A unique mouse model of multiple myeloma (MM), namely 5T2MM-bearing mouse, was useful for elucidating the pathophysiological mechanisms underlying the disease. Increased accumulation of suppressive CD4(+)CD25(High)Foxp3(+) regulatory T cells (Tregs) was observed in the thymus and lymphoid peripheral organs during disease progression. Adoptive transfer of Tregs, but not other thymocytes, from 5T2MM-bearing mice led to increased progression of disease manifestations in young syngeneic mice. Depletion of Tregs, a proposed strategy in cancer immunotherapy, was tested using cyclophosphamide (CYC), an alkylating agent with selective cytotoxicity. Both low- and high-dose CYC, administered to sick mice with hind limb paralysis, caused the paralysis to disappear, th... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=3486776 Tue, 20 Apr 2010 18:24:03 +0100 3486776 http://www.medworm.com/index.php?rid=3486775&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20399960%26dopt%3DAbstract Authors: Drabkin HA, Gemmill RM Multiple epidemiologic studies have linked the development of renal cancer to obesity. In this chapter, we begin with a review of selected population studies, followed by recent mechanistic discoveries that further link lipid deregulation to the RCC development. The upregulation of leptin and downregulation of adiponectin pathways in obesity fit well with our molecular understanding of RCC pathogenesis. In addition, two forms of hereditary RCC involve proteins, Folliculin and TRC8, that are positioned to coordinately regulate lipid and protein biosynthesis. Both of these biosynthetic pathways have important downstream consequences on HIF-1/2alpha levels and angiogenesis, key aspects in the disease pathogenesis. The role of lipid biology and its interface... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=3486775 Tue, 20 Apr 2010 18:24:03 +0100 3486775 http://www.medworm.com/index.php?rid=3486774&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20399961%26dopt%3DAbstract Authors: Mougiakakos D, Choudhury A, Lladser A, Kiessling R, Johansson CC At the present time, regulatory T cells (Tregs) are an integral part of immunology but the route from discovery of "suppressive" lymphocytes in the 1980s to the current established concept of Tregs almost 20 years later has been a rollercoaster ride. Tregs are essential for maintaining self-tolerance as defects in their compartment lead to severe autoimmune diseases. This vitally important function exists alongside the detrimental effects on tumor immunosurveillance and antitumor immunity. Beginning with the identification of CD4(+)CD25(+) Tregs in 1995, the list of Treg subsets, suppressive mechanisms, and knowledge about their various origins is steadily growing. Increase in Tregs within tumors and circulation ... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=3486774 Tue, 20 Apr 2010 18:24:03 +0100 3486774 http://www.medworm.com/index.php?rid=3486772&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20399962%26dopt%3DAbstract Authors: Iwakiri D, Takada K Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) are noncoding RNAs that are expressed abundantly in latently EBV-infected cells. Previous studies demonstrated that EBERs (EBER1 and EBER2) play significant roles in various EBV-infected cancer cells. EBERs are responsible for malignant phenotypes of Burkitt's lymphoma (BL) cells including resistance to apoptosis. In addition, EBERs induce the expression of interleukin (IL)-10 in BL cells, insulin-like growth factor (IGF)-1 in gastric carcinoma and nasopharyngeal carcinoma cells, IL-9 in T cells that act as an autocrine growth factor. It was also reported that EBERs play critical roles in the B cell growth transformation including IL-6 induction by EBER2. EBERs have been discovered to interact with cellula... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=3486772 Tue, 20 Apr 2010 18:24:03 +0100 3486772 http://www.medworm.com/index.php?rid=3486771&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20399963%26dopt%3DAbstract Authors: Lamont KR, Tindall DJ The biological action of androgenic male sex steroid hormones in prostate tissue is mediated by the androgen receptor, a nuclear transcription factor. The transcriptional program of androgenic signaling in the prostate consists of thousands of gene targets whose products play a role in almost all cellular functions, including cellular proliferation, survival, lipid metabolism, and differentiation. This review will provide a summary of the most recent data regarding androgen-regulated target genes and modulation of androgen receptor activity, especially with regard to androgen-dependent and castration-recurrent prostate cancer. PMID: 20399963 [PubMed - in process] (Source: Advances in Cancer Research) Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=3486771 Tue, 20 Apr 2010 18:24:03 +0100 3486771 http://www.medworm.com/index.php?rid=3486770&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20399964%26dopt%3DAbstract Authors: Albihn A, Johnsen JI, Henriksson MA MYC proteins (c-MYC, MYCN, and MYCL) regulate processes involved in many if not all aspects of cell fate. Therefore, it is not surprising that the MYC genes are deregulated in several human neoplasias as a result from genetic and epigenetic alterations. The near "omnipotency" together with the many levels of regulation makes MYC an attractive target for tumor intervention therapy. Here, we summarize some of the current understanding of MYC function and provide an overview of different cancer forms with MYC deregulation. We also describe available treatments and highlight novel approaches in the pursuit for MYC-targeting therapies. These efforts, at different stages of development, constitute a promising platform for novel, more specific trea... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=3486770 Tue, 20 Apr 2010 18:24:03 +0100 3486770 http://www.medworm.com/index.php?rid=3130349&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19854351%26dopt%3DAbstract Authors: Cuevas I, Boudreau N It is now well established both experimentally and clinically, that new blood vessel growth is required for tumors to grow beyond a few millimeters and metastasize [Folkman, J. (1995). In: Mendelsohn, L., Howley, P., Israel, A. (Eds.), The Molecular Basis of Cancer, WB Saunders Company, Philadelphia, pp. 206-225]. Angiogenesis, the process of forming new blood vessels from preexisting vessels, provides the tumor with additional oxygen and nutrients for its continued growth. In addition, the proximity and increase in vascular density enhance the likelihood of tumor cells entering the bloodstream to eventually metastasize. Since the initial observations of Dr. Folkman in the late 1970s, research over the past 30 years has focused intensely on identifying poi... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=3130349 Thu, 31 Dec 2009 13:12:06 +0100 3130349 http://www.medworm.com/index.php?rid=2955401&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19878769%26dopt%3DAbstract Authors: Bettuzzi S Since the beginning, Clusterin (CLU) was revealed not as simple to study, and certainly not a single protein. The growing research interest on CLU soon produced many contributions by independent laboratories working in different systems. Thus, many different names or acronyms have been given to CLU in the early years after its discovery. Now, a general consensus recommend the name Clusterin and the abbreviation CLU. CLU was first described as a glycoprotein found nearly ubiquitous in tissues and body fluids. This early knowledge is mostly related to the secretory form of CLU (sCLU), which is exported from the cell and released in secretions acting as an extracellular chaperone. But CLU can also enter the nucleus. The detection of nCLU (nuclear CLU), which is usually... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2955401 Wed, 04 Nov 2009 02:42:03 +0100 2955401 http://www.medworm.com/index.php?rid=2955400&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19878770%26dopt%3DAbstract Authors: Rizzi F, Coletta M, Bettuzzi S Clusterin (CLU) has kept many researchers engaged for a long time since its first discovery and characterization in the attempt to unravel its biological role in mammals. Although there is a general consensus on the fact that CLU is supposed to play important roles in nearly all fundamental biological phenomena and in many human diseases including cancer, after about 10 years of work CLU has been defined as an "enigmatic" protein. This sense of frustration among the researchers is originated by the fact that, despite considerable scientific production concerning CLU, there is still a lack of basic information about the complex regulation of its expression. The CLU gene is a single 9-exon gene expressed at very different levels in almost all major... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2955400 Wed, 04 Nov 2009 02:42:03 +0100 2955400 http://www.medworm.com/index.php?rid=2955399&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19878771%26dopt%3DAbstract Authors: Pucci S, Bettuzzi S Cell transformation is strictly linked to important metabolic changes which are instrumental for initial survival of cancer cells and subsequent spreading of disease. Early (i.e., anerobic glycolysis) and late metabolic changes (i.e., fatty acid metabolism) are required for progression and clinical emergence of cancer. Besides well-known tumor suppressors and oncogenes, several metabolic genes have been found implicated in this multistep process, among which are fatty acid synthase (FASN) and carnitine palmitoyl transferase I (CPT I). An intriguing link between these metabolic shifts and a change in the balance between nuclear and secreted forms of CLU (nCLU/sCLU) has been suggested. The shifting balance between CLU forms during tumor progression, by affect... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2955399 Wed, 04 Nov 2009 02:42:03 +0100 2955399 http://www.medworm.com/index.php?rid=2955398&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19878772%26dopt%3DAbstract In conclusion, a narrow range of intracellular Ca(2+) concentrations is responsible for the decision whether nCLU is mobilized (apoptosis) or sCLU is appointed to improve survival. Since the discovery of CLU, a huge research progress has been done. Nonetheless we feel that much work is left ahead before remaining uncertainties related to Ca(2+) signal and the respective roles of CLU proteins are unraveled. PMID: 19878772 [PubMed - in process] (Source: Advances in Cancer Research) Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2955398 Wed, 04 Nov 2009 02:42:03 +0100 2955398 http://www.medworm.com/index.php?rid=2955397&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19878773%26dopt%3DAbstract Authors: Bettuzzi S, Rizzi F The possible biological role played by Clusterin (CLU) has been puzzling researchers for a long time since its first discovery and characterization. CLU has been often described as an "enigmatic" gene, a clear indication that too many aspects of this issue have been obscure or difficult to interpret for long. The good news is that this is certainly no longer true. Since the beginning, CLU was believed to play important roles in nearly all most important biological phenomena. The diversity, sometime the contradictions, of its biological action is now likely explained by the existence of different protein products all generated by the same single copy CLU gene. The relatively recent discovery that CLU can be retained inside the cell and targeted to many intra... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2955397 Wed, 04 Nov 2009 02:42:03 +0100 2955397 http://www.medworm.com/index.php?rid=2955396&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19878774%26dopt%3DAbstract Authors: Wyatt A, Yerbury J, Poon S, Dabbs R, Wilson M The function(s) of clusterin may depend upon its topological location. A variety of intracellular "isoforms" of clusterin have been reported but further work is required to better define their identity. The secreted form of clusterin has a potent ability to inhibit both amorphous and amyloid protein aggregation. In the case of amorphous protein aggregation, clusterin forms stable, soluble high-molecular-weight complexes with misfolded client proteins. Clusterin expression is increased during many types of physiological and pathological stresses and is thought to function as an extracellular chaperone (EC). The pathology of a variety of serious human diseases is thought to arise as a consequence of the inappropriate aggregation of s... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2955396 Wed, 04 Nov 2009 02:42:03 +0100 2955396 http://www.medworm.com/index.php?rid=2955395&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19878775%26dopt%3DAbstract Authors: Klock G, Baiersdörfer M, Koch-Brandt C Secretory clusterin (sCLU) is found as an 80-kDa glycoprotein in virtually all body fluids, in serum it is associated with high-density lipoprotein (HDL). Here, we discuss demonstrated and proposed mechanisms of the cytoprotective functions of sCLU in instances of apoptosis, necrosis, and disease. These include prevention from cell damage by lipid oxidation in blood vessels, removal of dead cell remnants in tissues undergoing various forms of cell death, and clearance of harmful extracellular molecules such as amyloid beta (Abeta) by endocytosis or transcytosis. All these functions may reflect the propensity of sCLU to bind to a wide spectrum of hydrophobic molecules on one hand and to specific cell-surface receptors on the other han... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2955395 Wed, 04 Nov 2009 02:42:03 +0100 2955395 http://www.medworm.com/index.php?rid=2955394&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19878776%26dopt%3DAbstract Authors: Falgarone G, Chiocchia G For years, clusterin has been recognized as a secreted protein and a large number of works demonstrated that this ubiquitously expressed protein has multiple activities. Among the described activities several were related to inflammation and immunity such as its regulatory activity on complement. Then it became clear that a nuclear form of the protein with proapoptotic property existed and more recently that a cytoplasmic form could regulate NF-kappaB pathway. Again, these activities have a strong repercussion in inflammation and immunity. On the other hand, data available on the exact role of CLU in these processes and autoimmunity were quite scarce until recently. Indeed, in the last few years, a differential CLU expression in subtype of T cells, the... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2955394 Wed, 04 Nov 2009 02:42:03 +0100 2955394 http://www.medworm.com/index.php?rid=2955393&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19878777%26dopt%3DAbstract Authors: Trougakos IP, Gonos ES Clusterin/Apolipoprotein J (CLU) gene is expressed in most human tissues and encodes for two protein isoforms; a conventional heterodimeric secreted glycoprotein and a truncated nuclear form. CLU has been functionally implicated in several physiological processes as well as in many pathological conditions including ageing, diabetes, atherosclerosis, degenerative diseases, and tumorigenesis. A major link of all these, otherwise unrelated, diseases is that they are characterized by increased oxidative injury due to impaired balance between production and disposal of reactive oxygen or nitrogen species. Besides the aforementioned diseases, CLU gene is differentially regulated by a wide variety of stimuli which may also promote the production of reactive spe... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2955393 Wed, 04 Nov 2009 02:42:03 +0100 2955393 http://www.medworm.com/index.php?rid=2955392&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19879420%26dopt%3DAbstract Authors: Rizzi F, Bettuzzi S The role of clusterin (CLU) in prostate tumorigenesis is probably the most highly controversial, with evidence that CLU expression is increased or decreased in different cancer models. For example, some studies showed that CLU expression is increased in advanced stages of prostate cancer and that suppression of CLU expression sensitizes prostate cancer cells to chemotherapeutic drugs killing. In contrast with the hypothesis that CLU is a positive modulator of prostate cancer, we and others have observed that CLU is downregulated during human prostate cancer progression. Accordingly, a meta-analysis of available microarray data shows that CLU mRNA is significantly downregulated in prostate cancer tissue compared to normal prostate in 14 out of 15 independent... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2955392 Wed, 04 Nov 2009 02:42:03 +0100 2955392 http://www.medworm.com/index.php?rid=2955391&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19879421%26dopt%3DAbstract Authors: Redondo M, Tellez T, Roldan MJ Breast cancer is the main cause of cancer-related death among women in Western countries. Current research is focused on identifying antiapoptotic proteins which could be a possible target for novel chemotherapeutic drugs. Secretory clusterin (sCLU) is an extracellular chaperone that has been functionally implicated in DNA repair, cell-cycle regulation, apoptotic cell death and tumorigenesis. The implication of sCLU in carcinogenesis and the progression of breast carcinomas make it an interesting gene, worthy of investigation. It has been reported to present powerful antiapoptotic activity and to perform a prosurvival function with most therapeutic treatments for breast cancer. This review summarizes our current understanding of the role of CLU i... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2955391 Wed, 04 Nov 2009 02:42:03 +0100 2955391 http://www.medworm.com/index.php?rid=2955390&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19879422%26dopt%3DAbstract Authors: Mazzarelli P, Pucci S, Spagnoli LG The transition from normal to malignant phenotype implies the activation of some pathways that underlie the aberrant clone expansion. In some way, the conventional function of proteins involved in DNA repair, cell death/growth induction, vascularization, and metabolism is inhibited or shifted toward other pathways by soluble mediators that orchestrate such change depending on the microenvironment conditions. The adenoma-carcinoma sequence of the colon represents one of the most well studied and characterized models of human tumor progression. In this section, we focus our attention on defined pathways that underlie the initiation, promotion, and progression of colon cancer, conferring aggressiveness to the neoplastic cells. Clusterin (CLU) is... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2955390 Wed, 04 Nov 2009 02:42:03 +0100 2955390 http://www.medworm.com/index.php?rid=2955389&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19879423%26dopt%3DAbstract Authors: Panico F, Rizzi F, Fabbri LM, Bettuzzi S, Luppi F Lung cancer is the leading cause of cancer-related mortality. It is categorized into two histological groups that have distinct clinical behaviors, the nonsmall cell lung cancers (NSCLC) and the small cell lung cancer (SCLC). When identified at an early stage, NSCLC is treated by surgical resection. However, patients who undergo surgical resection still have a relative low survival rate, primarily for tumor recurrence. Unfortunately, advances in cytotoxic therapy have reached a plateau and new approaches to treatment are needed together with new and better parameters for more accurate prediction of the outcome and more precise indication of the efficacy of the treatment. Several in vitro studies have examined the role of Cluste... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2955389 Wed, 04 Nov 2009 02:42:03 +0100 2955389 http://www.medworm.com/index.php?rid=2955388&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19879424%26dopt%3DAbstract Authors: Djeu JY, Wei S Resistance to anticancer agents is one of the primary impediments to effective cancer therapy. Chemoresistance occurs not only to clinically established therapeutic agents but also to novel targeted therapeutics. Both intrinsic and acquired mechanisms have been implicated in drug resistance but it remains controversial which mechanisms are responsible that lead to failure of therapy in cancer patients. Recent focus has turned to clusterin (CLU) as a key contributor to chemoresistance to anticancer agents. Its role has been documented in prostate cancer for paclitaxel/docetaxel resistance as well as in renal, breast, and lung tumor cells. Moreover, it is abnormally upregulated in numerous advanced stage and metastatic cancers spanning prostate, renal, bladder, br... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2955388 Wed, 04 Nov 2009 02:42:03 +0100 2955388 http://www.medworm.com/index.php?rid=2955387&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19879425%26dopt%3DAbstract CLU "in and out": looking for a link. Adv Cancer Res. 2009;105:93-113 Authors: Pucci S, Mazzarelli P, Nucci C, Ricci F, Spagnoli LG Cancer cells need to interact synergistically with their surrounding microenvironment to form a neoplasm and to progress further to colonize distant organs. The microenvironment can exert profound epigenetic effects on cells through cell-derived interactions between cells, or through cell-derived factors deposited into the microenvironment. Tumor progression implies immune-escaping and triggers several processes that synergistically induce a cooperation among transformed and stromal cells, that compete for space and resources such as oxygen and nutrients. Therefore, the extra cellular milieu and tissue microenvironment heterotypic interactions coop... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2955387 Wed, 04 Nov 2009 02:42:03 +0100 2955387 http://www.medworm.com/index.php?rid=2955386&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19879426%26dopt%3DAbstract Authors: Sala A, Bettuzzi S, Pucci S, Chayka O, Dews M, Thomas-Tikhonenko A In no other field has the function of clusterin (CLU) been more controversial than in cancer genetics. After more than 20 years of research, there is still uncertainty with regard to the role of CLU in human cancers. Some investigators believe CLU to be an oncogene, others-an inhibitor of tumorigenesis. However, owing to the recent efforts of several laboratories, the role of CLU in important cellular processes like proliferation, apoptosis, differentiation, and transformation is beginning to emerge. The "enigmatic" CLU is becoming less so. In this chapter, we will review the work of research teams interested in understanding how CLU is regulated by oncogenic signaling. We will discuss how and under what circum... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2955386 Wed, 04 Nov 2009 02:42:03 +0100 2955386 http://www.medworm.com/index.php?rid=2955385&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19879427%26dopt%3DAbstract Authors: Bettuzzi S Since its first discovery, CLU has been fascinating many researchers around the world, probably because CLU has always been a surprise. In many studies, CLU showed up unexpected as a secondary but significant observation in the hands of scientists which probably had no specific intention to study it. Too often the first descriptions of the structure, action, and biological meaning of CLU had to be changed in the light of novel and rather surprising findings, making what was thought to be well established, actually obsolete. CLU is a biological object still in movement. To understand more, we will have to cope correctly with this challenge. As an Ariadne's thread, following CLU we will challenge our static ideas pointing to alternative views which will possibly lead ... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2955385 Wed, 04 Nov 2009 02:42:03 +0100 2955385 http://www.medworm.com/index.php?rid=2931341&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19854350%26dopt%3DAbstract Authors: Hanna JA, Bordeaux J, Rimm DL, Agarwal S The hepatocyte growth factor (HGF) and its receptor, the Met receptor tyrosine kinase, form a signaling network promoting cell proliferation, invasion, and survival in normal and cancer cells. Improper regulation of this pathway is attributed to many cancer types through overexpression, activating mutations, or autocrine loop formation. Many studies describe the localization of Met as membranous/cytoplasmic, but some studies using antibodies targeted to the C-terminal domain of Met report nuclear localization. This chapter seeks to highlight the histopathology and expression of Met in cancer and its association with clinicopathological characteristics. We also discuss recent studies of the proteolytic processing of Met and effects of th... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2931341 Tue, 27 Oct 2009 17:24:02 +0100 2931341 http://www.medworm.com/index.php?rid=2931340&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19854351%26dopt%3DAbstract Authors: Cuevas I, Boudreau N It is now well established both experimentally and clinically, that new blood vessel growth is required for tumors to grow beyond a few millimeters and metastasize [Folkman, J. (1995). In: Mendelsohn, L., Howley, P., Israel, A. (Eds.), The Molecular Basis of Cancer, WB Saunders Company, Philadelphia, pp. 206-225]. Angiogenesis, the process of forming new blood vessels from preexisting vessels, provides the tumor with additional oxygen and nutrients for its continued growth. In addition, the proximity and increase in vascular density enhance the likelihood of tumor cells entering the bloodstream to eventually metastasize. Since the initial observations of Dr. Folkman in the late 1970s, research over the past 30 years has focused intensely on identifying poi... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2931340 Tue, 27 Oct 2009 17:24:02 +0100 2931340 http://www.medworm.com/index.php?rid=2931339&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19854352%26dopt%3DAbstract Authors: Rahman M, Pumphrey JG, Lipkowitz S Breast cancers can be classified into those which express the estrogen (ER) and progesterone (PR) receptors, those with HER-2 amplification, and those without expression of ER, PR, or amplified HER-2 (referred to as triple-negative or basal-like breast cancer). Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) activates apoptosis upon binding to its receptors in many tumor types and the ligand and agonist antibodies are currently being studied in patients in clinical phases I and II trials. Cell line studies suggest that many breast cancer cell lines are very resistant to TRAIL-induced apoptosis. However, recent data suggest that a subset of triple-negative/basal-like breast cancer cells is sensitive to TRAIL as a single agent. ... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2931339 Tue, 27 Oct 2009 17:24:02 +0100 2931339 http://www.medworm.com/index.php?rid=2931338&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19854353%26dopt%3DAbstract Authors: Benhenda S, Cougot D, Buendia MA, Neuveut C Despite the existence of effective vaccines, HBV infection remains a major health problem with 2 billion people infected worldwide. Among them, 350 million are chronically infected, a major risk factor for the development of hepatocellular carcinoma (HCC). There is a strong need to develop new and efficient treatments against chronic infection and HCC. It is therefore important to understand HBV replication and persistence as well as the role of HBV in liver carcinogenesis. This chapter focuses on the regulatory protein HBx which is thought to play a central role in HBV regulation and pathogenesis. HBx has been shown to modulate a myriad of viral and cellular functions, yet its role in virus replication and pathogenesis in infected i... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2931338 Tue, 27 Oct 2009 17:24:02 +0100 2931338 http://www.medworm.com/index.php?rid=2931337&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19854354%26dopt%3DAbstract Authors: Gallant P Myc genes play a major role in human cancer, and they are important regulators of growth and proliferation during normal development. Despite intense study over the last three decades, many aspects of Myc function remain poorly understood. The identification of a single Myc homolog in the model organism Drosophila melanogaster more than 10 years ago has opened new possibilities for addressing these issues. This review summarizes what the last decade has taught us about Myc biology in the fruit fly. PMID: 19854354 [PubMed - in process] (Source: Advances in Cancer Research) Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2931337 Tue, 27 Oct 2009 17:24:02 +0100 2931337 http://www.medworm.com/index.php?rid=2825074&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19595310%26dopt%3DAbstract Authors: Mehrotra S, Mougiakakos D, Johansson CC, Voelkel-Johnson C, Kiessling R CD8(+) T cells respond to antigen stimulation through a process of activation, division, and differentiation generating a large pool of activated effector cytolytic T lymphocytes (CTLs). Many cancer patients harbor the accordant precursor CTLs capable of responding to various tumor-associated antigens (TAA). In selected cases, vaccination with these TAA can elicit detectable antitumor responses. Presently, the clinical outcome of cancer vaccination remains inadequate. The lack of clinical efficacy may be attributed to various molecular and cellular mechanisms developed by tumors to successfully evade the host immune system. Some of these mechanisms have been identified. It is becoming increasingly apparent... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2825074 Thu, 24 Sep 2009 08:08:03 +0100 2825074 http://www.medworm.com/index.php?rid=2603370&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19595305%26dopt%3DAbstract Authors: Young A, Lyons J, Miller AL, Phan VT, Alarcón IR, McCormick F More than 25 years have passed since activating mutations in Ras genes were identified in DNA from human tumors. In this time, it has been established beyond doubt that these mutations play a direct role in causing cancer, and do so in collaboration with a number of other oncogenes and tumor suppressors. Oncogenic mutant Ras proteins are resistant to downregulation by GAP-mediated hydrolysis of bound GTP, and therefore signal persistently. Efforts to develop therapies that block Ras oncoprotein function directly have failed. The high affinity of Ras proteins for GTP has discouraged attempts to identify GTP-analogs. Ras processing enzymes have been targeted, but unfortunately, K-Ras, the Ras protein that plays t... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2603370 Thu, 16 Jul 2009 09:06:03 +0100 2603370 http://www.medworm.com/index.php?rid=2603369&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19595306%26dopt%3DAbstract Authors: Jiang BH, Liu LZ Phosphatidylinositol 3-kinase (PI3K) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) signaling pathway play an important role in multiple cellular functions such as cell metabolism, proliferation, cell-cycle progression, and survival. PI3K is activated by growth factors and angiogenesis inducers such as vascular endothelial growth factor (VEGF) and angiopoietins. The amplification and mutations of PI3K and the loss of the tumor suppressor PTEN are common in various kinds of human solid tumors. The genetic alterations of upstream and downstream of PI3K signaling molecules such as receptor tyrosine kinases and AKT, respectively, are also frequently altered in human cancer. PI3K signaling regulates tumor growth and angiogenesis by activating AK... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2603369 Thu, 16 Jul 2009 09:06:03 +0100 2603369 http://www.medworm.com/index.php?rid=2603368&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19595307%26dopt%3DAbstract Authors: Hedley BD, Chambers AF Metastasis-the spread of cancer to distant organs-is responsible for most cancer deaths. Current adjuvant therapy is based on prognostic indicators that stratify patients into defined risk groups. However, some patients believed to have a good prognosis nonetheless develop metastases, in some cases many years after apparently successful treatment of their primary cancer. This period of clinical dormancy leads to many questions about how best to manage patients, including how to better assign risk of late recurrence, how long to monitor patients, and whether some patients will benefit from extended therapy to prevent late recurrences. The development of targeted therapies with fewer side effects is leading to clinical trials aimed at determining the effec... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2603368 Thu, 16 Jul 2009 09:06:03 +0100 2603368 http://www.medworm.com/index.php?rid=2603367&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19595308%26dopt%3DAbstract Authors: Kampranis SC, Tsichlis PN Epigenetic modifications are heritable chromatin alterations that contribute to the temporal and spatial interpretation of the genome. The epigenetic information is conveyed through a multitude of chemical modifications, including DNA methylation, reversible modifications of histones, and ATP-dependent nucleosomal remodeling. Deregulation of the epigenetic machinery contributes to the development of several pathologies, including cancer. Chromatin modifications are multiple and interdependent and they are dynamically modulated in the course of various biological processes. Combinations of chromatin modifications give rise to a complex code that is superimposed on the genetic code embedded into the DNA sequence to regulate cell function. This review ad... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2603367 Thu, 16 Jul 2009 09:06:03 +0100 2603367 http://www.medworm.com/index.php?rid=2603366&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19595309%26dopt%3DAbstract Authors: Leeuwen I, Lain S The role of sirtuins in cancer has recently stimulated both considerable interest and debate. It is becoming clear that some sirtuins deacetylate important tumor suppressors thereby impinging on their activity. Human SirT1, for instance, has been shown to deacetylate p53 in biochemical assays, and growing evidence indicates that it also performs this activity in cells. Since deacetylation of p53 correlates with a decreased p53 transcriptional function, it is conceivable that sirtuin inhibition could lead to improved tumor suppression. There are, however, still many open questions regarding, for example, whether sirtuins deacetylate those lysine residues in p53 that are critical for its activity. Preliminary observations also suggest that sirtuin-mediated modu... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2603366 Thu, 16 Jul 2009 09:06:03 +0100 2603366 http://www.medworm.com/index.php?rid=2603365&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19595310%26dopt%3DAbstract Authors: Mehrotra S, Mougiakakos D, Christian Johansson C, Voelkel-Johnson C, Kiessling R CD8(+) T cells respond to antigen stimulation through a process of activation, division, and differentiation generating a large pool of activated effector cytolytic T lymphocytes (CTLs). Many cancer patients harbor the accordant precursor CTLs capable of responding to various tumor-associated antigens (TAA). In selected cases, vaccination with these TAA can elicit detectable antitumor responses. Presently, the clinical outcome of cancer vaccination remains inadequate. The lack of clinical efficacy may be attributed to various molecular and cellular mechanisms developed by tumors to successfully evade the host immune system. Some of these mechanisms have been identified. It is becoming increasingly... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2603365 Thu, 16 Jul 2009 09:06:03 +0100 2603365 http://www.medworm.com/index.php?rid=2026469&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19055943%26dopt%3DAbstract Authors: Orian-Rousseau V, Ponta H Receptors tyrosine kinases (RTKs) and cell adhesion molecules (CAMs) present on the cell surface sense the surrounding environment and influence the fate of cells. For a long time, it was believed that these molecules were working independently and that the sole binding of a ligand was enough to activate the RTK. It is now apparent that there is, in fact, a very tight connection between RTKs and CAMs and that they work in concert. The CAMs influence the activation, the signaling, or the internalization of the RTKs. Some CAMs have similar functions and are therefore interchangeable. CD44 isoforms exemplify the flexibility of these interactions as they can collaborate with several RTKs and can also be substituted by other CAMs with similar functions. In... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2026469 Thu, 11 Dec 2008 08:40:22 +0100 2026469 http://www.medworm.com/index.php?rid=2026468&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19055948%26dopt%3DAbstract Authors: Cadogan M, Dalgleish AG Chronic generalized immune activation represents one of the most critical features determining progression to AIDS. This may result in the manifestation of malignancy, with lymphoma and Karposi's sarcoma being the first to be recognised. In this regard, the manifestation of lymphoma is very similar to that seen in transplant patients and those with graft versus host disease (GVHD) where both chronic immune activation and immune suppression are present. Unlike the latter conditions which involve HLA mismatch, the source of this phenomenon during HIV infection remains elusive. Despite a lifecycle adapted to the host and possessing a plethora of survival strategies, HIV promotes disease progression in a manner that is consistently associated with the HLA r... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2026468 Thu, 11 Dec 2008 08:40:22 +0100 2026468 http://www.medworm.com/index.php?rid=2026467&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19055949%26dopt%3DAbstract Authors: Pawelek JM, Chakraborty AK The cause of metastasis remains elusive despite vast information on cancer cells. We posit that cancer cell fusion with macrophages or other migratory bone marrow-derived cells (BMDCs) provides an explanation. BMDCs fused with tumor cells were present in animal tumor xenografts where they were associated with metastases. In myeloma patients, transcriptionally active myeloma nuclei were incorporated into osteoclasts through fusion. In patients with renal cell carcinoma arising poststem cell transplant, donor genes were incorporated in recipient cancer cell nuclei, most likely through fusion, and showed tumor distribution patterns characteristic of cancer stem cells. Melanoma-macrophage hybrids generated in vitro contained chromosomes from both parenta... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2026467 Thu, 11 Dec 2008 08:40:22 +0100 2026467 http://www.medworm.com/index.php?rid=2017306&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19055940%26dopt%3DAbstract Authors: Ha VL, Luo R, Nie Z, Randazzo PA Arf GAPs are a family of proteins with a common catalytic domain that induces hydrolysis of GTP bound to the small GTP-binding protein Arf. The proteins are otherwise structurally diverse. Several subtypes of Arf GAPs have been found to be targets of oncogenes and to control cell proliferation and cell migration. The latter effects are thought to be mediated by coordinating changes in actin remodeling and membrane traffic. In this chapter, we discuss Arf GAPs that have been linked to oncogenesis and the molecular mechanisms underlying the effects of these proteins in cancer cells. We also discuss the enzymology of the Arf GAPs related to possible targeted inhibition of specific subtypes of Arf GAPs. PMID: 19055940 [PubMed - as supplied by p... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2017306 Sun, 07 Dec 2008 08:51:08 +0100 2017306 http://www.medworm.com/index.php?rid=2017305&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19055941%26dopt%3DAbstract Authors: Cheng SY, Yue S Originally identified as factors affecting Drosophila embryogenesis, the Hedgehog (Hh) pathway is one of the primary signaling systems that specify patterns of cell growth and differentiation during vertebrate development. Mutations in various components of this pathway frequently occur in tumors originated from the skin, cerebellum, and skeletal muscle, and abnormal pathway activity is associated with a subset of lung, digestive tract, pancreatic, and prostate cancers. Because of these potent biological activities, this pathway is negatively regulated at multiple levels to ensure appropriate signaling responses. Suppressor of fused (Sufu) is one such negative regulator of Hh signaling. Although not essential in Drosophila, Sufu is absolutely required for mouse... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2017305 Sun, 07 Dec 2008 08:51:08 +0100 2017305 http://www.medworm.com/index.php?rid=2017304&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19055942%26dopt%3DAbstract Authors: Li S, Hua ZC Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase that localizes to cellular focal adhesions or cell contacts within the extracellular matrix. FAK is activated by a variety of cell surface receptors and transmits signals to a range of targets. FAK participates in growth factor receptor-mediated signaling pathways and plays essential roles in cell survival, proliferation, migration, and invasion. In the present chapter, the mechanisms of FAK activation, the modulation of FAK function by phosphorylation, and the mechanisms regulating FAK expression are reviewed. Overexpression of FAK is widely observed in numerous tumor types, and is used as a marker for invasion and metastasis. FAK could be therapeutically targeted at various levels, such as at ... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2017304 Sun, 07 Dec 2008 08:51:08 +0100 2017304 http://www.medworm.com/index.php?rid=2017303&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19055943%26dopt%3DAbstract Authors: Orian-Rousseau V, Ponta H Receptors tyrosine kinases (RTKs) and cell adhesion molecules (CAMs) present on the cell surface sense the surrounding environment and influence the fate of cells. For a long time, it was believed that these molecules were working independently and that the sole binding of a ligand was enough to activate the RTK. It is now apparent that there is, in fact, a very tight connection between RTKs and CAMs and that they work in concert. The CAMs influence the activation, the signaling, or the internalization of the RTKs. Some CAMs have similar functions and are therefore interchangeable. CD44 isoforms exemplify the flexibility of these interactions as they can collaborate with several RTKs and can also be substituted by other CAMs with similar functions. In... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2017303 Sun, 07 Dec 2008 08:51:08 +0100 2017303 http://www.medworm.com/index.php?rid=2017302&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19055944%26dopt%3DAbstract Authors: Christensen KL, Patrick AN, McCoy EL, Ford HL The homeobox gene superfamily encodes transcription factors that act as master regulators of development through their ability to activate or repress a diverse range of downstream target genes. Numerous families exist within the homeobox gene superfamily, and are classified on the basis of conservation of their homeodomains as well as additional motifs that contribute to DNA binding and to interactions with other proteins. Members of one such family, the Six family, form a transcriptional complex with Eya and Dach proteins, and together these proteins make up part of the retinal determination network first identified in Drosophila. This network is highly conserved in both invertebrate and vertebrate species, where it influences the... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2017302 Sun, 07 Dec 2008 08:51:08 +0100 2017302 http://www.medworm.com/index.php?rid=2017301&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19055945%26dopt%3DAbstract Authors: Sionov RV, Spokoini R, Kfir-Erenfeld S, Cohen O, Yefenof E Glucocorticoids (GCs) are commonly used in the treatment of hematopoietic malignancies owing to their ability to induce apoptosis of these cancerous cells. Whereas some types of lymphoma and leukemia respond well to this drug, others are resistant. Also, GC-resistance gradually develops upon repeated treatments ultimately leading to refractory relapsed disease. Understanding the mechanisms regulating GC-induced apoptosis is therefore uttermost important for designing novel treatment strategies that overcome GC-resistance. This review discusses updated data describing the complex regulation of the cell's susceptibility to apoptosis triggered by GCs. We address both the genomic and nongenomic effects involved in promotin... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2017301 Sun, 07 Dec 2008 08:51:08 +0100 2017301 http://www.medworm.com/index.php?rid=2017300&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19055946%26dopt%3DAbstract Authors: Seliger B, Ruiz-Cabello F, Garrido F Interferons represent a protein family with pleiotropic functions including immunomodulatory, cytostatic, and cytotoxic activities. Based on these effects, interferons are involved in innate as well as adaptive immunity, thereby shaping the tumor host immune responses. These cytokines, alone or in combination, have been successfully implemented for the treatment of some malignancies. However, it has been recently demonstrated that tumor cells could be resistant to interferon treatment, which may be associated with an escape of tumor cells from immune surveillance. Therefore, the aim of this chapter is to summarize the frequency of impaired interferon signal transduction, their underlying molecular mechanisms, and their clinical relevance. ... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2017300 Sun, 07 Dec 2008 08:51:08 +0100 2017300 http://www.medworm.com/index.php?rid=2017299&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19055947%26dopt%3DAbstract Authors: Terabe M, Berzofsky JA NKT cells are a relatively newly recognized member of the immune community, with profound effects on the rest of the immune system despite their small numbers. They are true T cells with a T cell receptor (TCR), but unlike conventional T cells that detect peptide antigens presented by conventional major histocompatibility (MHC) molecules, NKT cells recognize lipid antigens presented by CD1d, a nonclassical MHC molecule. As members of both the innate and adaptive immune systems, they bridge the gap between these, and respond rapidly to set the tone for subsequent immune responses. They fill a unique niche in providing the immune system a cellular arm to recognize lipid antigens. They play both effector and regulatory roles in infectious and autoimmune dis... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2017299 Sun, 07 Dec 2008 08:51:08 +0100 2017299 http://www.medworm.com/index.php?rid=2017298&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19055948%26dopt%3DAbstract Authors: Cadogan M, Dalgleish AG Chronic generalized immune activation represents one of the most critical features determining progression to AIDS. This may result in the manifestation of malignancy, with lymphoma and Karposi's sarcoma being the first to be recognised. In this regard, the manifestation of lymphoma is very similar to that seen in transplant patients and those with graft versus host disease (GVHD) where both chronic immune activation and immune suppression are present. Unlike the latter conditions which involve HLA mismatch, the source of this phenomenon during HIV infection remains elusive. Despite a lifecycle adapted to the host and possessing a plethora of survival strategies, HIV promotes disease progression in a manner that is consistently associated with the HLA r... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2017298 Sun, 07 Dec 2008 08:51:08 +0100 2017298 http://www.medworm.com/index.php?rid=2017297&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19055949%26dopt%3DAbstract Authors: Pawelek JM, Chakraborty AK The cause of metastasis remains elusive despite vast information on cancer cells. We posit that cancer cell fusion with macrophages or other migratory bone marrow-derived cells (BMDCs) provides an explanation. BMDCs fused with tumor cells were present in animal tumor xenografts where they were associated with metastases. In myeloma patients, transcriptionally active myeloma nuclei were incorporated into osteoclasts through fusion. In patients with renal cell carcinoma arising poststem cell transplant, donor genes were incorporated in recipient cancer cell nuclei, most likely through fusion, and showed tumor distribution patterns characteristic of cancer stem cells. Melanoma-macrophage hybrids generated in vitro contained chromosomes from both parenta... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=2017297 Sun, 07 Dec 2008 08:51:08 +0100 2017297 http://www.medworm.com/index.php?rid=1634756&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18620090%26dopt%3DAbstract Authors: Klein G, Vande Woude GF PMID: 18620090 [PubMed - in process] (Source: Advances in Cancer Research) Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=1634756 Fri, 18 Jul 2008 09:28:13 +0100 1634756 http://www.medworm.com/index.php?rid=1630753&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18620090%26dopt%3DAbstract Authors: Woude GV PMID: 18620090 [PubMed - in process] (Source: Advances in Cancer Research) Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=1630753 Thu, 17 Jul 2008 09:44:12 +0100 1630753 http://www.medworm.com/index.php?rid=1630752&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18620091%26dopt%3DAbstract Authors: Wagh PK, Peace BE, Waltz SE The Ron receptor is a member of the Met family of cell surface receptor tyrosine kinases and is primarily expressed on epithelial cells and macrophages. The biological response of Ron is mediated by binding of its ligand, hepatocyte growth factor-like protein/macrophage stimulating-protein (HGFL). HGFL is primarily synthesized and secreted from hepatocytes as an inactive precursor and is activated at the cell surface. Binding of HGFL to Ron activates Ron and leads to the induction of a variety of intracellular signaling cascades that leads to cellular growth, motility and invasion. Recent studies have documented Ron overexpression in a variety of human cancers including breast, colon, liver, pancreas, and bladder. Moreover, clinical studies have als... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=1630752 Thu, 17 Jul 2008 09:44:12 +0100 1630752 http://www.medworm.com/index.php?rid=1630751&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18620092%26dopt%3DAbstract Authors: Linger RM, Keating AK, Earp HS, Graham DK Tyro-3, Axl, and Mer constitute the TAM family of receptor tyrosine kinases (RTKs) characterized by a conserved sequence within the kinase domain and adhesion molecule-like extracellular domains. This small family of RTKs regulates an intriguing mix of processes, including cell proliferation/survival, cell adhesion and migration, blood clot stabilization, and regulation of inflammatory cytokine release. Genetic or experimental alteration of TAM receptor function can contribute to a number of disease states, including coagulopathy, autoimmune disease, retinitis pigmentosa, and cancer. In this chapter, we first provide a comprehensive review of the structure, regulation, biologic functions, and downstream signaling pathways of these rece... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=1630751 Thu, 17 Jul 2008 09:44:12 +0100 1630751 http://www.medworm.com/index.php?rid=1630750&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18620093%26dopt%3DAbstract Authors: Fre S, Vignjevic D, Schoumacher M, Duffy SL, Janssen KP, Robine S, Louvard D In this review, the major signal transduction pathways that have been shown to play an important role in intestinal homeostasis are highlighted. Each of them, the Wnt, Notch, Hedgehog, and Bone Morphogenetic Protein, as well as growth-factor regulated Receptor Tyrosine Kinases are depicted with a special emphasis through their involvement in stem cell maintenance and their role in intestinal tumorigenesis. Finally, we discuss recent data on the final steps of tumor progression, notably the formation of distant metastases. This multistep process is highly complex and still far from being understood while being of major importance for the survival of patients with digestive cancer. PMID: 18620093 [P... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=1630750 Thu, 17 Jul 2008 09:44:12 +0100 1630750 http://www.medworm.com/index.php?rid=1630749&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18620094%26dopt%3DAbstract Authors: Cao Y Bevacizumab (Avastin), a vascular endothelial growth factor antagonist, is the first approved antiangiogenic drug for the treatment of human cancers. Endostatin, a broad-spectrum endogenous angiogenesis inhibitor, has recently been approved in China for cancer therapy. Today, hundreds of antiangiogenic molecules targeting different signaling pathways are being tested for their anticancer efficacies at preclinical and clinical stages. The underlying mechanisms by which these antiangiogenic cancer drugs used in combination with chemotherapy confer survival advantages for cancer patients are not fully understood. Thus, deeper understanding the mechanisms of tumor angiogenesis and actions of these therapeutic molecules is crucial for designing more potent anticancer drugs. ... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=1630749 Thu, 17 Jul 2008 09:44:12 +0100 1630749 http://www.medworm.com/index.php?rid=1630748&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18620095%26dopt%3DAbstract Authors: Blum B, Benvenisty N Human embryonic stem cells (HESCs) are the in vitro descendants of the pluripotent inner cell mass (ICM) of human blastocyst stage embryos. HESCs can be kept undifferentiated in culture or be differentiated to tissues representing all three germ layers, both in vivo and in vitro. These properties make HESC-based therapy remarkably appealing for the treatment of various disorders. Upon transplantation in vivo, undifferentiated HESCs rapidly generate the formation of large tumors called teratomas. These are benign masses of haphazardly differentiated tissues. Teratomas also appear spontaneously in humans and in mice. When they also encompass a core of malignant undifferentiated cells, these tumors are defined as teratocarcinomas. These malignant undifferenti... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=1630748 Thu, 17 Jul 2008 09:44:12 +0100 1630748 http://www.medworm.com/index.php?rid=1630747&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18620096%26dopt%3DAbstract Authors: Rubin H A comprehensive listing with accompanying discussions is given for established cases of interactions between normal and neoplastic cells of the same histotype that suppress neoplastic development. General principles that apply to the process are: (a) the requirement for a large excess of normal cells in direct contact with the neoplastic cells; (b) the effectiveness of suppression decreases with the degree of malignant progression of the neoplastic cells; and (c) the transformability of normal cells decreases under long-term negative selection, which also increases their contact suppression of neoplastic cells. Although suppression requires adhesive contact, it does not require gap junction communication, and it represents the first line of defense against tumor develo... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=1630747 Thu, 17 Jul 2008 09:44:12 +0100 1630747 http://www.medworm.com/index.php?rid=1630746&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18620097%26dopt%3DAbstract Authors: Witz IP The interaction between microenvironmental components and tumor cells is bidirectional. Tumor cells and their products are capable of regulating and altering gene expression in nontumor cells residing in or infiltrating into the microenvironment and exert selective pressures on such cells, thereby shaping their phenotype. Conversely, microenvironmental components regulate gene expression in tumor cells thereby directing the tumor into one or several possible molecular evolution pathways, some of which may lead to metastasis. This review summarizes six instances in which the tumor liaises with different components of its microenvironment. These liaisons result, in most cases, in enhanced tumor progression. In these cases (responses of tumor and nontumor cells to microen... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=1630746 Thu, 17 Jul 2008 09:44:12 +0100 1630746 http://www.medworm.com/index.php?rid=1142232&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18037405%26dopt%3DAbstract Authors: Svoboda J This chapter provides a personal insight into the scientific and social atmosphere in former Czechoslovakia. It covers the period of the rise of Hasek's immunologic school and application of immunologic tolerance to Rous sarcoma virus (RSV) heterotransmission. These approaches permitted establishment of a new model of mammalian cells transformed by RSV (virogenic XC cells), where the noninfectious viral genome was kept indefinitely as new genetic information (provirus). RSV was rescued from nonpermissive mammalian cells by fusion (complementation) with permissive chicken fibroblasts; this opened the way to understanding virus nonpermissiveness. Mammalian cells transformed by the reverse transcript of v-src mRNA were characterized, and the resulting provirus was shown... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=1142232 Fri, 11 Jan 2008 00:26:55 +0100 1142232 http://www.medworm.com/index.php?rid=1051983&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18037405%26dopt%3DAbstract Authors: Svoboda J This chapter provides a personal insight into the scientific and social atmosphere in former Czechoslovakia. It covers the period of the rise of Hasek's immunologic school and application of immunologic tolerance to Rous sarcoma virus (RSV) heterotransmission. These approaches permitted establishment of a new model of mammalian cells transformed by RSV (virogenic XC cells), where the noninfectious viral genome was kept indefinitely as new genetic information (provirus). RSV was rescued from nonpermissive mammalian cells by fusion (complementation) with permissive chicken fibroblasts; this opened the way to understanding virus nonpermissiveness. Mammalian cells transformed by the reverse transcript of v-src mRNA were characterized, and the resulting provirus was shown... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=1051983 Tue, 27 Nov 2007 14:03:31 +0100 1051983 http://www.medworm.com/index.php?rid=1051982&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18037406%26dopt%3DAbstract Authors: Ito Y Mouse embryonal carcinoma (EC) cells, also called teratocarcinoma stem cells, are nonpermissive for polyomavirus growth, whereas differentiated derivatives of the cells are permissive. Mutant viruses capable of growing in EC cells can be isolated. They have genomic alterations within the viral enhancer, which is required for viral gene expression and DNA replication. This viral regulatory region was considered as a potential probe for mouse cell differentiation. The 24-bp-long A element within the enhancer was identified as a minimum element, which also shows a lower activity in EC cells compared with the differentiated cells. Transcription factors PEA1/AP1, PEA2/PEBP2, and PEA3/ETS were identified as A element-binding proteins. All of them are absent in EC cells and ind... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=1051982 Tue, 27 Nov 2007 14:03:30 +0100 1051982 http://www.medworm.com/index.php?rid=1051981&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18037407%26dopt%3DAbstract Authors: Yasuda J, Hayashizaki Y Recent progress in the analyses of the mouse transcriptome leads to unexpected discoveries. The mouse genomic sequences read by RNA polymerase II may be six times more than previously expected for human chromosomes. The transcript-abundant regions (named "transcription forests") occupy more than half of the genomic sequence and are divided by transcript-scarce regions (transcription deserts). Many of the coding mRNAs may have partially overlapping antisense RNAs. There are transcripts bridging several adjacent genes that were previously regarded as distinct ones. The transcription start sites appearing as cap analysis of gene expression (CAGE) tags are mapped on the mouse genomic sequences. Distributions of CAGE tags show that the shapes of mammalian ge... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=1051981 Tue, 27 Nov 2007 14:03:27 +0100 1051981 http://www.medworm.com/index.php?rid=1051980&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18037408%26dopt%3DAbstract Authors: Wierstra I, Alves J The transcription factor c-Myc is a key regulator of cell proliferation, cell growth, differentiation, and apoptosis. Deregulated c-myc expression possesses a high transformation potential and the proto-oncogene c-myc represents a promising target in anticancer therapy. This review on the c-myc promoter describes its organization, the different levels of its normal regulation (including initiation and elongation of transcription, the dual P1/P2 promoters, chromatin structure, c-Myc autosuppression) as well as its deregulation in Burkitt's lymphoma. Furthermore, it summarizes the many different transcription factors, signal transduction pathways, and feedback loops that activate or repress c-myc transcription. Finally, a concept for regulation of the c-myc p... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=1051980 Tue, 27 Nov 2007 14:03:25 +0100 1051980 http://www.medworm.com/index.php?rid=1051979&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18037409%26dopt%3DAbstract Authors: Zhang S Biomedical researchers have become increasingly aware of the limitations of the conventional 2-D tissue cell cultures where most tissue cell studies including cancer and tumor cells have been carried out. They are now searching and testing 3-D cell culture systems, something between a petri dish and a mouse. The important implications of 3-D tissue cell cultures for basic cell biology, tumor biology, high-content drug screening, and regenerative medicine and beyond are far-reaching. How can nanobiotechnology truly advance the traditional cell, tumor, and cancer biology? Why nano is important in biomedical research and medical science? A nanometer is 1000 times smaller than a micrometer, but why it matters in biology? This chapter addresses these questions. It has becom... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=1051979 Tue, 27 Nov 2007 14:03:24 +0100 1051979 http://www.medworm.com/index.php?rid=1051978&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18037410%26dopt%3DAbstract Authors: Vulink A, Radford KJ, Melief C, Hart DN Since their discovery, there has been significant progress in the understanding of dendritic cell (DC) biology. Their capacity for priming an immune response against pathogens and cancers has been exploited clinically. However, the objective responses obtained to date using DC cancer vaccines have been modest. Suboptimal DC preparations, limited tumor target antigens, and the essential need to initiate trials in immunocompromised patients with advanced disease, have all contributed to limited outcomes. The use of fully activated DCs, loaded with multiple, immunogenic, cancer-specific antigens, administered to patients with minimal residual disease and the manipulation of regulatory mechanisms underlying peripheral tolerance, may be the i... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=1051978 Tue, 27 Nov 2007 14:03:22 +0100 1051978 http://www.medworm.com/index.php?rid=568724&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17433907%26dopt%3DAbstract Authors: Potter M Plasma cell tumors (PCTs) in mice became available at an exciting period in immunology when many scientists and laboratories were occupied with how to explain the genetic basis of antibody diversity as well as antibody structure itself. An unlimited source of PCTs in an inbred strain of mice became a useful adjunct in these efforts. A PCT was a greatly expanded monoclone and a source of a single molecular species of immunoglobulin (Ig) molecule. The PCTs provided not only the components of the Ig-producing cell but also potentially functional secreted products. Many of the monoclonal Igs produced by PCTs in the mouse and others found in humans were found to have specific antigen-binding activities. These became the prototypes of monoclonal antibodies. This chapter des... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=568724 Wed, 25 Apr 2007 19:00:02 +0100 568724 http://www.medworm.com/index.php?rid=549715&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17433906%26dopt%3DAbstract Authors: Klein G, Imreh S, Zabarovsky ER Traditionally, surveillance against cancer was thought of as mainly immunological. With the exception of tumors with a clear viral involvement, such as immunoblastomas (Epstein-Barr virus, EBV), cervical, anogenital, and skin carcinomas (HPV), and Kaposi's sarcoma (HHV-8) where the immune system is confronted with virally encoded, nonself targets, tumors with no viral involvement provide poor targets. Attempts to influence them by immunological means are akin to the breaking of tolerance. Robust nonimmunological surveillance mechanisms include DNA repair-based checkpoint functions, and the triggering of growth arrest and/or apoptosis pathways by DNA damage or by illegitimate oncogene activation (intracellular surveillance). There is emerging evi... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=549715 Wed, 18 Apr 2007 04:16:02 +0100 549715 http://www.medworm.com/index.php?rid=549714&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17433907%26dopt%3DAbstract Authors: Potter M Plasma cell tumors (PCTs) in mice became available at an exciting period in immunology when many scientists and laboratories were occupied with how to explain the genetic basis of antibody diversity as well as antibody structure itself. An unlimited source of PCTs in an inbred strain of mice became a useful adjunct in these efforts. A PCT was a greatly expanded monoclone and a source of a single molecular species of immunoglobulin (Ig) molecule. The PCTs provided not only the components of the Ig-producing cell but also potentially functional secreted products. Many of the monoclonal Igs produced by PCTs in the mouse and others found in humans were found to have specific antigen-binding activities. These became the prototypes of monoclonal antibodies. This chapter des... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=549714 Wed, 18 Apr 2007 04:16:02 +0100 549714 http://www.medworm.com/index.php?rid=549713&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17433908%26dopt%3DAbstract Authors: Cardiff RD, Kenney N For over a century, mouse mammary tumor biology and the associated Mouse mammary tumor virus (MMTV) have served as the foundation for experimental cancer research, in general, and, in particular, experimental breast cancer research. Spontaneous mouse mammary tumors were the basis for studies of the natural history of neoplasia, oncogenic viruses, host responses, endocrinology, and neoplastic progression. However, lacking formal proof of a human mammary tumor virus, the preeminence of the mouse model faded in the 1980s. Since the late 1980s, genetically engineered mice (GEM) have proven extremely useful for studying breast cancer and have become the animal model for human breast cancer. Hundreds of mouse models of human breast cancer have been developed sin... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=549713 Wed, 18 Apr 2007 04:16:02 +0100 549713 http://www.medworm.com/index.php?rid=549712&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17433909%26dopt%3DAbstract Authors: Rubin H Ordered heterogeneity was introduced as a basic feature of the living state in the mid-1950s. It was later expanded to "order in the large over heterogeneity in the small" as the first principle of a theory of organisms. Several examples of ordered heterogeneity were given at the time to illustrate the principle, but many more have become apparent since then to confirm its generality. They include minimum size requirements for progressive embryological development, the errant behavior of cells liberated from tissue architecture, their sorting out to reconstitute tissues on reaggregation, and contact regulation of cell proliferation. There is increasing heterogeneity of cell growth with age, and marked heterogeneity of many characters among cells of solid epithelial tum... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=549712 Wed, 18 Apr 2007 04:16:02 +0100 549712 http://www.medworm.com/index.php?rid=549711&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17433910%26dopt%3DAbstract Authors: Baritaki S, Apostolakis S, Kanellou P, Dimanche-Boitrel MT, Spandidos DA, Bonavida B In recent years, significant development and improvement have been observed in the treatment of cancer; however, relapses and recurrences occur frequently and there have not been any current therapies to treat such cancers. Cancers resistant to conventional therapies develop several mechanisms to escape death-inducing stimuli. A poorly understood mechanism is the involvement of the cancer cell plasma membrane composition and architecture and their involvement in regulating drug-inducing stimuli leading to cell death. Although the basic structure of the biological membrane was established 80 years ago, study of the physical properties of lipid bilayers still provides significant information reg... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=549711 Wed, 18 Apr 2007 04:16:02 +0100 549711 http://www.medworm.com/index.php?rid=549710&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17433911%26dopt%3DAbstract Authors: Hu J, Zhou GB, Wang ZY, Chen SJ, Chen Z Mutations in transcription factors (TFs) and protein tyrosine kinases (PTKs), which result in inhibition of differentiation/apoptosis or enhanced proliferative/survival advantage of hematopoietic stem/progenitor cells, are two classes of the most frequently detected genetic abnormalities in leukemias. The critical roles for mutant TFs and/or PTKs to play in leukemogenesis, and the absence of mutant TFs/PTKs in normal hematopoietic cells, suggest that the two types of aberrant molecules may serve as ideal therapeutic targets. The great success of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) in treating acute promyelocytic leukemia through modulation of the causative PML-RARalpha oncoprotein represents the first two paradigms ... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=549710 Wed, 18 Apr 2007 04:16:02 +0100 549710 http://www.medworm.com/index.php?rid=549709&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17433912%26dopt%3DAbstract Authors: Labat-Robert J, Robert L The malignant process, transformation of normal cells, proliferation, and metastasis formation, was considered as if originating from one single cell. Although the intrinsic mechanisms of transformation from the normal to the malignant state were both confirmed, an increasing body of evidence points to the surrounding matrix and cell-matrix interactions as major players in this process. Some of the most important arguments in favor of this contention are cited and commented in this chapter. Another important question concerns the relationship between the aging process and malignant transformation. A few decades ago, the frequency of clinically manifest tumors of several organs and tissues appeared to increase with age. As, however, average life expecta... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=549709 Wed, 18 Apr 2007 04:16:02 +0100 549709 http://www.medworm.com/index.php?rid=537337&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17419939%26dopt%3DAbstract Authors: Joerger AC, Fersht AR The tumor suppressor protein p53 is a transcription factor that plays a key role in the prevention of cancer development. In response to oncogenic or other stresses, the p53 protein is activated and regulates the expression of a variety of target genes, resulting in cell cycle arrest, senescence, or apoptosis. Mutation of the p53 gene is the most common genetic alteration in human cancer, affecting more than 50% of human tumors. Most of these mutations inactivate the DNA-binding domain of the protein. In this chapter, we describe the structure of the wild-type p53 protein and present structural and functional data that provide the molecular basis for understanding the effects of common cancer mutations. Further, we assess novel therapeutic strategies that... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=537337 Wed, 11 Apr 2007 21:08:02 +0100 537337 http://www.medworm.com/index.php?rid=537336&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17419940%26dopt%3DAbstract Authors: Ringdén O During the past three decades, allogeneic stem cell transplantation (ASCT) has developed from being an experimental therapy in patients with endstage leukemia into a well-established therapy in patients with a range of disorders of the immunohematopoietic system. Graft-versus-host disease (GVHD), acute or chronic, attacking host tissue is a major threat. However, donor immunocompetent T cells have a potent graft-versus-leukemia effect. A combination of calcineurin inhibitors and methotrexate is the standard therapy to prevent GVHD. Modulation of the immunosuppressive regimen may induce mild acute and mild chronic GVHD, reduce the risk of relapse, and improve long-term survival. Natural killer cells also play a role in this context. Killer cell immunoglobulin-like re... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=537336 Wed, 11 Apr 2007 21:08:02 +0100 537336 http://www.medworm.com/index.php?rid=537335&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17419941%26dopt%3DAbstract Authors: Wahlström T, Henriksson M Myc is the most frequently deregulated oncogene in human tumors. The protein belongs to the Myc/Max/Mxd network of transcriptional regulators important for cell growth, proliferation, differentiation, and apoptosis. The ratio between Mnt/Max and c-Myc/Max on the 5'-CACGTG-3' E-box sequence at shared target genes is of great importance for cell cycle progression and arrest. Serum stimulation of quiescent cells results in phosphorylation of Mnt and disruption of the critical Mnt-mSin3-HDAC1 interaction. This in turn leads to increased expression of the Myc/Mnt target gene cyclin D2. It is therefore possible that Myc function relies on its ability to overcome transcriptional repression by Mnt and that relief of Mnt-mediated transcriptional repression is... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=537335 Wed, 11 Apr 2007 21:08:02 +0100 537335 http://www.medworm.com/index.php?rid=537334&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17419942%26dopt%3DAbstract Authors: Miller G, El-Guindy A, Countryman J, Ye J, Gradoville L The seminal experiments of George and Eva Klein helped to define the two life cycles of Epstein-Barr Virus (EBV), namely latency and lytic or productive infection. Their laboratories described latent nuclear antigens expressed during latency and discovered several chemicals that activated the viral lytic cycle. The mechanism of the switch between latency and the lytic cycle of EBV and Kaposi's sarcoma-associated herpesvirus (KSHV) can be studied in cultured B cell lines. Lytic cycle activation of EBV is controlled by two viral transcription factors, ZEBRA and Rta. The homologue of Rta encoded in ORF50 is the lytic cycle activator of KSHV. Control of the lytic cycle can be divided into two distinct phases. Upstream events ... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=537334 Wed, 11 Apr 2007 21:08:02 +0100 537334 http://www.medworm.com/index.php?rid=537333&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17419943%26dopt%3DAbstract Authors: Krammer PH, Kamiński M, Kießling M, Gülow K Apoptosis-programed cell death-is the most common form of death in the body. Once apoptosis is induced, proper execution of the cell death program requires the coordinated activation and execution of multiple molecular processes. Here, we describe the pathways and the basic components of the death-inducing machinery. Since apoptosis is a key regulator of tissue homeostasis, an imbalance of apoptosis results in severe diseases like cancer, autoimmunity, and AIDS. PMID: 17419943 [PubMed - as supplied by publisher] (Source: Advances in Cancer Research) Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=537333 Wed, 11 Apr 2007 21:08:02 +0100 537333 http://www.medworm.com/index.php?rid=537332&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17419944%26dopt%3DAbstract Authors: Jernberg-Wiklund H, Nilsson K Human multiple myeloma (MM) is characterized by the expansion of neoplastic plasmablasts/plasma cells with complex genetic aberrations and high dependence for survival and growth on cytokines produced in the bone marrow microenvironment. As tools in the study of MM about 80 authentic MM cell lines and a few relevant in vivo mouse models are available. The dependence on insulin-like growth factor receptor (IGF-IR) signaling in the development and maintenance of the malignant phenotype in a variety of cancers is a rationale for attempts to improve tumor treatment by selectively inhibiting the IGF-IR in malignant cells by neutralizing antibodies, dominant negative IGF-IR, and IGF-IR siRNA. Testing the hypothesis that abrogating IGF-IR-mediated signal... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=537332 Wed, 11 Apr 2007 21:08:02 +0100 537332 http://www.medworm.com/index.php?rid=537331&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17419945%26dopt%3DAbstract Authors: Schlee M, Schuhmacher M, Hölzel M, Laux G, Bornkamm GW Deregulation of c-myc expression through chromosomal translocation is essential in the pathogenesis of Burkitt's lymphoma (BL). A characteristic feature of BL cells, compared to Epstein-Barr Virus (EBV)-immortalized B cells, is their lack of immunogenicity. To study the contribution of EBV genes and of the c-MYC protein to this phenotype, we have generated a conditional B cell system in which the viral proliferation program and expression of c-myc can be regulated independently of each other. In cells proliferating due to exogenous c-myc overexpression, the cell surface phenotype, the pattern of proliferation in single cell suspension, and the immunological characteristics of BL cells could be completely recapitulated. Ye... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=537331 Wed, 11 Apr 2007 21:08:02 +0100 537331 http://www.medworm.com/index.php?rid=537330&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17419946%26dopt%3DAbstract Authors: Rabinovsky R, Uhr JW, Vitetta ES, Yefenof E Cancer dormancy delineates a situation in which residual tumor cells persist in a patient with no apparent clinical symptoms. Although the precise mechanisms underlying cancer dormancy have not been explained, experimental models have provided some insights into the factors that might be involved in the induction and maintenance of a tumor dormant state. The authors of the present chapter studied a murine B cell lymphoma that can be made dormant when interacting with antibodies directed against the idiotype on its immunoglobulin Ig receptor. This experimental model of antibody-induced dormancy enabled the isolation and characterization of dormant lymphoma cells. The results indicated that anti-Ig antibodies activate growth-inhibiting... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=537330 Wed, 11 Apr 2007 21:08:02 +0100 537330 http://www.medworm.com/index.php?rid=537327&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17419947%26dopt%3DAbstract Authors: Cao Y, Liu Q Like any growing healthy tissues, tumors build up their blood vessels by three mechanisms: angiogenesis, vasculogenesis, and intersucception. Vascular endothelial growth factor-A (VEGF-A) is one of the key factors responsible for stimulation and maintenance of the disorganized, leaky, and torturous tumor vasculature. In addition to VEGF-A, tumors produce multiple other factors to stimulate blood vessel growth. These include members in the platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), VEGF-C, insulin-like growth factor (IGF), angiopoietin (Ang), and hepatocyte growth factor (HGF) families. Recent studies show that these angiogenic factors can also promote lymphangiogenesis and potentially lymphatic metastasis. Understanding the roles of ind... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=537327 Wed, 11 Apr 2007 21:08:02 +0100 537327 http://www.medworm.com/index.php?rid=537326&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17419948%26dopt%3DAbstract Authors: Yates C, Shepard CR, Papworth G, Dash A, Beer Stolz D, Tannenbaum S, Griffith L, Wells A Metastatic seeding leads to most of the morbidity from carcinomas. However, little is known of this key event as current methods to study the cellular behaviors utilize nonrepresentative in vitro models or follow indirect subsequent developments in vivo. Therefore, we developed a system to visualize over a multiday to multiweek period the interactions between tumor cells and target organ parenchyma. We employ an ex vivo microscale perfusion culture system that provides a tissue-relevant environment to assess metastatic seeding behavior. The bioreactor recreates many features of the fluid flow, scale, and biological functionality of a hepatic parenchyma, a common site of metastatic spread f... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=537326 Wed, 11 Apr 2007 21:08:02 +0100 537326 http://www.medworm.com/index.php?rid=537325&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17419949%26dopt%3DAbstract Authors: Ostman A, Heldin CH Signaling through platelet-derived growth factor (PDGF) receptors contributes to multiple tumor-associated processes. The recent introduction of clinically useful PDGF inhibitors have the last years validated PDGF receptors in malignant and stromal cells as relevant cancer drug targets. Mutational activation of PDGF receptor signaling in malignant cells has been described in some rare tumor types such as dermatofibrosarcoma protuberans, a subset of GISTs, and some hematologic malignancies. Furthermore, expression of PDGF receptors on pericytes is a common characteristic of solid tumors. The clinical efficacy of novel multikinase inhibitors, such as sunitinib and sorafenib, most likely involves targeting of PDGF receptor-dependent pericytes. Preclinical stud... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=537325 Wed, 11 Apr 2007 21:08:02 +0100 537325 http://www.medworm.com/index.php?rid=537324&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17419950%26dopt%3DAbstract Authors: Spencer VA, Xu R, Bissell MJ Almost three decades ago, we presented a model where the extracellular matrix (ECM) was postulated to influence gene expression and tissue-specificity through the action of ECM receptors and the cytoskeleton. This hypothesis implied that ECM molecules could signal to the nucleus and that the unit of function in higher organisms was not the cell alone, but the cell plus its microenvironment. We now know that ECM invokes changes in tissue and organ architecture and that tissue, cell, nuclear, and chromatin structure are changed profoundly as a result of and during malignant progression. Whereas some evidence has been generated for a link between ECM-induced alterations in tissue architecture and changes in both nuclear and chromatin organization, the... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=537324 Wed, 11 Apr 2007 21:08:02 +0100 537324 http://www.medworm.com/index.php?rid=537323&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17419951%26dopt%3DAbstract Authors: Klein S, Levitzki A Signal transduction therapy for cancer targets specific molecular elements that are essential for survival of the tumor. Gleevec has a profound effect on early phase chronic myeloid leukemia because it inhibits the major driving factor of the tumor, BCR-ABL. Almost all other cancers depend on several factors, and blocking a single signal transduction factor is largely ineffective. Effective signal transduction therapy will entail finding the appropriate combination of signal transduction inhibitors for each cancer. We discuss the use of preclinical animal models to predict successful signal transduction therapy in the clinic, and conclude that their utility is limited. PMID: 17419951 [PubMed - in process] (Source: Advances in Cancer Research) Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=537323 Wed, 11 Apr 2007 21:08:02 +0100 537323 http://www.medworm.com/index.php?rid=537322&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17419952%26dopt%3DAbstract Authors: Wiman KG The p53 tumor suppressor gene is mutated in around 50% of all human tumors. Most mutations inactivate p53's specific DNA binding, resulting in failure to activate transcription of p53 target genes. As a consequence, mutant p53 is unable to trigger a p53-dependent biological response, that is cell cycle arrest and apoptosis. Many tumors express high levels of nonfunctional mutant p53. Several strategies for restoration of wild-type p53 function in tumors have been designed. Wild-type p53 reconstitution by adenovirus-mediated gene transfer has shown antitumor efficacy in clinical trials. Screening of chemical libraries has allowed identification of small molecules that reactivate mutant p53 and trigger mutant p53-dependent apoptosis. These novel strategies raise hopes f... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=537322 Wed, 11 Apr 2007 21:08:02 +0100 537322 http://www.medworm.com/index.php?rid=369602&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17161674%26dopt%3DAbstract Authors: Mok SC, Elias KM, Wong KK, Ho K, Bonome T, Birrer MJ Ovarian cancer is the fifth most common form of cancer in women in the United States. It is a complex disease composed of different histological grades and histological types. Most of epithelial ovarian cancer cases are detected at an advanced stage. Patients usually respond to primary treatment with surgery and chemotherapy. However, the disease usually recurs and is ultimately fatal. So far, a satisfactory screening procedure and regime to treat the recurrence disease are not available. High-throughput genomic analyses have the potential to change the detection and the treatment of ovarian neoplasms. They can help diagnose subtypes of disease and predict patient survival. New diagnostic and prognostic markers for ovarian c... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369602 Mon, 05 Feb 2007 18:49:02 +0100 369602 http://www.medworm.com/index.php?rid=369601&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17161675%26dopt%3DAbstract Authors: van der Merwe DE, Oikonomopoulou K, Marshall J, Diamandis EP Despite impressive scientific achievements over the past few decades, cancer is still a leading cause of death. One of the major reasons is that most cancer patients are diagnosed with advanced disease. This is clearly illustrated with ovarian cancer in which the overall 5-year survival rates are only 20-30%. Conversely, when ovarian cancer is detected early (stage 1), the 5-year survival rate increases to 95%. Biomarkers, as tools for preclinical detection of cancer, have the potential to revolutionize the field of clinical diagnostics. The emerging field of clinical proteomics has found applications across a wide spectrum of cancer research. This chapter will focus on mass spectrometry as a proteomic technology imp... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369601 Mon, 05 Feb 2007 18:49:02 +0100 369601 http://www.medworm.com/index.php?rid=369600&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17161676%26dopt%3DAbstract Authors: Sears C, Armstrong SA Over the past decade, microarrays have emerged as an important tool for the characterization of cancer cells. Numerous studies have demonstrated that cDNA arrays can help delineate biological subsets of disease that have prognostic relevance. Such studies provide hope that introduction of this information into clinical trials will lead to more biologically based stratification schemes such that appropriately tailored therapies can be developed. While the identification of unique subsets of cancer promises to improve our ability to predict which cancers are unlikely to have a significant response to therapy, new therapeutic approaches are needed in most cases. The wealth of information that comes from microarray analysis of cancer likely holds the informat... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369600 Mon, 05 Feb 2007 18:49:02 +0100 369600 http://www.medworm.com/index.php?rid=369599&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17161677%26dopt%3DAbstract Authors: Fuchs U, Borkhardt A RNA interference (RNAi) is a naturally occurring cellular defense mechanism against viral infections and transposon invasion. Short double-stranded RNA molecules, so-called small-interfering (si)RNAs, bind their complementary mRNA leading to the mRNA's degradation. During the past few years, RNAi has become a valuable tool for transient as well as stable repression of gene expression rendering the time-consuming production of knockout animals superfluous. In this chapter the usability of the RNAi technology in cancer research will be described, focusing on the application of large-scale screens for identification of new components in cancer-relevant signal pathways (e.g., p53, RAS). The screens are especially helpful in the detection of potential anticance... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369599 Mon, 05 Feb 2007 18:49:02 +0100 369599 http://www.medworm.com/index.php?rid=369598&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17161678%26dopt%3DAbstract Authors: Li QX, Tan P, Ke N, Wong-Staal F Ribozymes are naturally occurring RNAs with catalytic activities including cis- or trans- cleavage of RNA at predefined sequence sites. This activity has been exploited for specific gene inactivation in cells during the last two decades, and ribozymes have been important functional genomics tools, especially in the pre-RNAi era. It has also been broadly applied in drug target identification and validation in pharmaceutical R&D. This chapter covers many application principles and case studies of ribozyme technology in the areas of cancer research. We also described RNAi applications in some of the same studies for comparison. Although RNAi may be more effective than ribozymes in many respects, they are nonetheless built on many of the same p... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369598 Mon, 05 Feb 2007 18:49:02 +0100 369598 http://www.medworm.com/index.php?rid=369597&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17161679%26dopt%3DAbstract Authors: Caldwell JS This chapter focuses on the promising post-genomic technologies being used for discovery of new, safer, and better cancer drugs and drug targets. Since cancer is largely a disease of the cell, usually involving unrestricted cell proliferation as a result of heritable genetic changes such as mutation, this chapter will focus on cell-centric technologies and their utility in addressing major questions in cancer biology. Recent advances in cell-based technology, including phenotypic assays, image-based readouts, primary tumor cell growth and maintenance in vitro, gene and small molecule delivery tools, and automated systems for cell manipulation, provide a novel means to understand the etiology and mechanisms of cancer as never before. In addition to the abundant tool... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369597 Mon, 05 Feb 2007 18:49:02 +0100 369597 http://www.medworm.com/index.php?rid=369596&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17161680%26dopt%3DAbstract Authors: Dalgleish A, Pandha H There are a large number of tumor antigens, which may either be specific to the tumor or inappropriately expressed or processed (tumor-associated antigen, TAA). Over the last few years, hundreds of new TAAs have been identified. Some of these represent good targets for both passive (antibody based) and active (vaccine based) therapies. Antibody treatments targeted on tumor-specific antigens, such as Herceptin and Cetuximab, have been effective in clinical trials and are now licensed. In addition, TAAs act as good surrogate markers for use in both the diagnosis and assessment of treatment in cancer patients. PMID: 17161680 [PubMed - indexed for MEDLINE] (Source: Advances in Cancer Research) Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369596 Mon, 05 Feb 2007 18:49:02 +0100 369596 http://www.medworm.com/index.php?rid=369595&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17161681%26dopt%3DAbstract Authors: Kung AL Mouse models of cancer are critical tools for elucidating mechanisms of cancer development, as well as for assessment of putative cancer therapies. However, there are ongoing concerns about the value of mouse cancer models for predicting therapeutic efficacy in humans. This chapter reviews the most commonly used transplanted tumor models, including subcutaneous and orthotopic tumors in mice. It also reviews commonly utilized in vivo study endpoints. Even small improvements in predictive value achieved through careful selection of models and endpoints have the potential to have large impacts on productivity and overall drug development costs. PMID: 17161681 [PubMed - indexed for MEDLINE] (Source: Advances in Cancer Research) Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369595 Mon, 05 Feb 2007 18:49:02 +0100 369595 http://www.medworm.com/index.php?rid=369594&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17161682%26dopt%3DAbstract Authors: Sarker D, Workman P Rational and efficient development of new molecular cancer therapeutics requires discovery, validation, and implementation of informative biomarkers. Measurement of molecular target status, pharmacokinetic (PK) parameters of drug exposure, and pharmacodynamic (PD) endpoints of drug effects on target, pathway, and downstream biological processes are extremely important. These can be linked to therapeutic effects in what we term a "pharmacological audit trail." Using biomarkers in preclinical drug discovery and development facilitates optimization of PK, PD, and therapeutic properties so that the best agent is selected for clinical evaluation. Applying biomarkers in early clinical trials helps identify the most appropriate patients; provides proof of concept ... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369594 Mon, 05 Feb 2007 18:49:02 +0100 369594 http://www.medworm.com/index.php?rid=369593&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17161683%26dopt%3DAbstract Authors: Lee JW, Figeys D, Vasilescu J Many candidate biomarkers emerging from genomics and proteomics research have the potential to serve as predictive indexes for guiding the development of safer and more efficacious drugs. Research and development of biomarker discovery, selection, and clinical qualification, however, is still a relatively new field for the pharmaceutical industry. Advances in technology provide a plethora of analytical tools to discover and analyze mechanism-and-disease-specific biomarkers for drug development. In the discovery phase, differential proteomic analysis using mass spectrometry enables the identification of candidate biomarkers that are associated with a specific mechanism relevant to disease progression and affected by drug treatment. Reliable bioanal... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369593 Mon, 05 Feb 2007 18:49:02 +0100 369593 http://www.medworm.com/index.php?rid=369592&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17161684%26dopt%3DAbstract We present the combination of optically active, targeted nanoparticles for molecular imaging with advances in minimally invasive optical imaging systems, which can be used to dynamically image both a molecular and phenotypic profile of risk and to monitor changes in this profile during therapy. PMID: 17161684 [PubMed - indexed for MEDLINE] (Source: Advances in Cancer Research) Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369592 Mon, 05 Feb 2007 18:49:02 +0100 369592 http://www.medworm.com/index.php?rid=369591&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17161685%26dopt%3DAbstract Authors: Sikora K PMID: 17161685 [PubMed - indexed for MEDLINE] (Source: Advances in Cancer Research) Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369591 Mon, 05 Feb 2007 18:49:02 +0100 369591 http://www.medworm.com/index.php?rid=369590&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17161686%26dopt%3DAbstract Authors: Milsted RA PMID: 17161686 [PubMed - indexed for MEDLINE] (Source: Advances in Cancer Research) Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369590 Mon, 05 Feb 2007 18:49:02 +0100 369590 http://www.medworm.com/index.php?rid=369689&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D11447765%26dopt%3DAbstract Authors: Shen Y, White E The p53 tumor suppressor limits cellular proliferation by inducing cell cycle arrest and apoptosis in response to cellular stresses such as DNA damage, hypoxia, and oncogene activation. Many apoptosis-related genes that are transcriptionally regulated by p53 have been identified. These are candidates for implementing p53 effector functions. In response to oncogene activation, p53 mediates apoptosis through a linear pathway involving bax transactivation, Bax translocation from the cytosol to membranes, cytochrome c release from mitochondria, and caspase-9 activation, followed by the activation of caspase-3, -6, and -7. p53-mediated apoptosis can be blocked at multiple death checkpoints, by inhibiting p53 activity directly, by Bcl-2 family members regulating mito... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369689 Mon, 22 Jan 2007 16:12:02 +0100 369689 http://www.medworm.com/index.php?rid=369688&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D11447766%26dopt%3DAbstract Authors: Clifford SC, Maher ER Von Hippel-Lindau (VHL) disease (MIM 193300) is the most common cause of familial clear cell renal cell carcinoma (RCC). VHL disease results from germline mutations in the VHL tumor suppressor gene and is characterized by variable expression and the development of benign and malignant neoplasms in multiple organs. The clinical management of VHL disease is challenging and requires a coordinated multidisciplinary approach. However, early detection of VHL tumors by annual surveillance has improved the prognosis for VHL gene carriers. Complex genotype-phenotype correlations for the major manifestations of VHL disease result from allelic heterogeneity and suggest that the VHL gene product has multiple and tissue-specific functions. Recent studies suggest that ... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369688 Mon, 22 Jan 2007 16:12:02 +0100 369688 http://www.medworm.com/index.php?rid=369687&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D11665716%26dopt%3DAbstract Authors: Piek E, Roberts AB Transforming growth factor-beta (TGF-beta) has been implicated in oncogenesis since the time of its discovery almost 20 years ago. The complex, multifunctional activities of TGF-beta endow it with both tumor suppressor and tumor promoting activities, depending on the stage of carcinogenesis and the responsivity of the tumor cell. Dysregulation or alteration of TGF-beta signaling in tumorigenesis can occur at many different levels, including activation of the ligand, mutation or transcriptional suppression of the receptors, or alteration of downstream signal transduction pathways resulting from mutation or changes in expression patterns of signaling intermediates or from changes in expression of other proteins which modulate signaling. New insights into signa... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369687 Mon, 22 Jan 2007 16:12:02 +0100 369687 http://www.medworm.com/index.php?rid=369686&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D11665717%26dopt%3DAbstract Authors: Garrido F, Algarra I PMID: 11665717 [PubMed - indexed for MEDLINE] (Source: Advances in Cancer Research) Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369686 Mon, 22 Jan 2007 16:12:02 +0100 369686 http://www.medworm.com/index.php?rid=369685&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D11665718%26dopt%3DAbstract Authors: Rubin H Mathematical modeling indicates that selective growth of cells with biallelic mutations in tumor suppressor genes is the driving force in the development of most human tumors, and that increased mutation rate is not required. Spontaneous neoplastic transformation of cells in culture offers the opportunity for quantitative analysis of all stages of neoplastic progression, the cellular variation that underlies it, and the selective conditions that promote it. Most of the early work on spontaneous transformation was done in primary cultures of mouse embryo cells, but established mouse cell lines have been used more in recent years. The main criteria for transformation have been tumorigenesis in mice, increase in saturation density, and production of discrete, multilayered... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369685 Mon, 22 Jan 2007 16:12:02 +0100 369685 http://www.medworm.com/index.php?rid=369684&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D11665719%26dopt%3DAbstract Authors: Shiloh Y, Kastan MB One of the cornerstones of the web of signaling pathways governing cellular life and differentiation is the DNA damage response. It spans a complex network of pathways, ranging from DNA repair to modulation of numerous processes in the cell. DNA double-strand breaks (DSBs), which are formed as a result of genotoxic stress or normal recombinational processes, are extremely lethal lesions that rapidly mobilize this intricate defense system. The master controller that pilots cellular responses to DSBs is the ATM protein kinase, which turns on this network by phosphorylating key players in its various branches. ATM is the protein product of the gene mutated in the human genetic disorder ataxia-telangiectasia (A-T), which is characterized by neuronal degeneratio... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369684 Mon, 22 Jan 2007 16:12:02 +0100 369684 http://www.medworm.com/index.php?rid=369683&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D11665720%26dopt%3DAbstract Authors: Dunbier A, Guilford P Hereditary diffuse gastric cancer (HDGC) is a cancer predisposition syndrome caused by germline mutation of the gene for the cell-to-cell adhesion protein E-cadherin. The syndrome is dominated by predisposition to the histologically diffuse, poorly differentiated form of gastric cancer. It is not associated with intestinal-type gastric cancer, but families may have an elevated risk of lobular breast cancer. Here, we review the identified families, mutations, and proposed mechanisms by which E-cadherin loss promotes tumorigenesis. PMID: 11665720 [PubMed - indexed for MEDLINE] (Source: Advances in Cancer Research) Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369683 Mon, 22 Jan 2007 16:12:02 +0100 369683 http://www.medworm.com/index.php?rid=369682&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D11665721%26dopt%3DAbstract Authors: Selva EM, Perrimon N PMID: 11665721 [PubMed - indexed for MEDLINE] (Source: Advances in Cancer Research) Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369682 Mon, 22 Jan 2007 16:12:02 +0100 369682 http://www.medworm.com/index.php?rid=369681&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D11665722%26dopt%3DAbstract Authors: Stevenson FK, Sahota SS, Ottensmeier CH, Zhu D, Forconi F, Hamblin TJ The classification of B cell tumors has relevance for refining and improving clinical strategies. However, consensus has been difficult to establish, and although a scheme is now available, objective criteria are desirable. Genetic technology will underpin and extend current knowledge, and it is certain to reveal further subdivisions of current tumor categories. The Ig variable region genes of B cell tumors present a considerable asset for this area of investigation. The unique sequences carried in neoplastic B cells are easily isolated and sequenced. In addition to acting as clone-specific markers of each tumor, they indicate where the cell has come from and track its history following transformation. There... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369681 Mon, 22 Jan 2007 16:12:02 +0100 369681 http://www.medworm.com/index.php?rid=369680&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D11883525%26dopt%3DAbstract Authors: Hedenfalk IA, Ringnér M, Trent JM, Borg A Large proportions of hereditary breast cancers are due to mutations in the two breast cancer susceptibility genes BRCA1 and BRCA2. Considerable effort has gone into studying the function(s) of these tumor suppressor genes, both in attempts to better understand why individuals with these inherited mutations acquire breast (and ovarian) cancer and to potentially develop better treatment strategies. The advent of tools such as cDNA microarrays has enabled researchers to study global gene expression patterns in, for example, primary tumors, thus providing more comprehensive overviews of tumor development and progression. Our recent study (Hedenfalk et al., 2001) strongly supports the principle that genomic approaches to classification of ... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369680 Mon, 22 Jan 2007 16:12:02 +0100 369680 http://www.medworm.com/index.php?rid=369679&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D11883526%26dopt%3DAbstract Authors: Collins CM, Medveczky PG Herpesviruses are large double-stranded DNA viruses that are characterized by lifelong latency. Epstein-Barr virus (EBV), the recently discovered Kaposi's sarcoma associated herpesvirus (KSHV), also referred to as human herpesvirus-8 (HHV-8), and the simian Herpesvirus saimiri (HVS) are associated with malignant lymphoproliferative diseases. These viruses establish latent infection in lymphoid cells. During latency only a few viral genes are expressed and the viral genome persists as a multicopy circular episome. The episome contains repetitive sequences that serve as multiple cooperative binding sites for the viral DNA binding proteins Epstein-Barr virus nuclear antigen 1 (EBNA-1) of EBV and latency-associated nuclear antigen (LANA1) of KSHV and HVS, ... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369679 Mon, 22 Jan 2007 16:12:02 +0100 369679 http://www.medworm.com/index.php?rid=369678&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D11883527%26dopt%3DAbstract Authors: Gottschalk S, Heslop HE, Roon CM Latent Epstein-Barr virus (EBV) infection is associated with a heterogeneous group of malignancies, including Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma, and lymphoproliferative disease (LPD). The development of adoptive immunotherapies for these malignancies is being fueled by the successful generation of allogeneic donor derived EBV-specific cytotoxic T cells (CTL) for the prevention and treatment of EBV-LPD after hematopoietic stem cell transplantation. This approach is being extended to EBV-LPD after solid organ transplantation by use of autologous and haploidentical EBV-specific CTL. For other EBV-associated malignancies, there is only limited clinical experience with EBV-specific CTL. With few exceptions, only patient... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369678 Mon, 22 Jan 2007 16:12:02 +0100 369678 http://www.medworm.com/index.php?rid=369677&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D11883528%26dopt%3DAbstract Authors: Manoukian AS, Woodgett JR Although glycogen synthase kinase-3 (GSK-3) is but one of more than a thousand distinct serine/threonine kinases present in the mammalian genome, this enzyme has attracted attention for its role in a diverse range of cellular processes and its positioning at a nexus of several signaling pathways that are important in cancer and other human diseases. The association of GSK-3 with widely different functions, from glycogen metabolism to fruit fly segmentation and slime mold differentiation, was initially perplexing. However, as the context of the biological processes involving this enzyme has been clarified, unifying themes have emerged that begin to explain its pleiotropic nature. Unlike most protein kinases involved in signaling, GSK-3 is active in uns... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369677 Mon, 22 Jan 2007 16:12:02 +0100 369677 http://www.medworm.com/index.php?rid=369676&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D11883529%26dopt%3DAbstract Authors: Dalgleish AG, O'Byrne KJ Infection with the human immunodeficiency virus (HIV) invariably leads to the development of acquired immunodeficiency syndrome (AIDS) in most infected humans, yet does so rarely, if at all, in HIV-infected chimpanzees. The differences between the two species are not due to differences in cellular receptors or an inability of the chimpanzee to be infected, but rather to the lack of pan-immune activation in the infected primate. This results in reduced apoptotic death in CD4+ T-helper lymphocytes and a lower viral load. In humans the degree of chronic immune activation correlates with virus load and clinical outcome with high immune activation leading to high viral loads and the more rapid progression to AIDS and death. The type of immune perturbation s... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369676 Mon, 22 Jan 2007 16:12:02 +0100 369676 http://www.medworm.com/index.php?rid=369675&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D11883530%26dopt%3DAbstract Authors: Küppers R Hodgkin's lymphoma (HL) is characterized by typical mononucleated Hodgkin and multinucleated Reed-Sternberg cells, which occur at low frequency in a mixed cellular infiltrate in the tumor tissue. Because of the rarity of these cells and their unusual immunophenotype, which is strikingly different from those of all normal hematopoietic cell types, the origin of these cells and their clonality have long been unclear. Single-cell studies of rearranged immunoglobulin genes showed that Hodgkin and Reed-Sternberg (HRS) cells represent clonal tumor-cell populations derived from germinal center B cells. In classical HL, the detection of obviously crippling immunoglobulin gene mutations in a fraction of the cases suggests that HRS cells may derive from germinal center B cell... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369675 Mon, 22 Jan 2007 16:12:02 +0100 369675 http://www.medworm.com/index.php?rid=369674&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D11883531%26dopt%3DAbstract Authors: Landberg G Breast cancer is one of the most common cancer forms affecting many women. The disease nevertheless has widely varying behavior and therefore patient outcome, and an important undertaking is to define and understand the molecular mechanisms behind these actions. Defects in the G1/S transition in the cell cycle affect both tumor proliferation and the fidelity of check points responsible for chromosomal integrity and DNA damage response and has lately been shown to represent one of a rather limited set of key aberrations in the transformation process. Many cell cycle regulatory proteins are either oncogenes or suppressor genes or are closely associated to the transformation process. The types of aberrations in the G1/S transition seem to be different in various cancer... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369674 Mon, 22 Jan 2007 16:12:02 +0100 369674 http://www.medworm.com/index.php?rid=369673&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D11883532%26dopt%3DAbstract Authors: Jaffe AB, Hall A During the development and progression of human cancer, cells undergo numerous changes in morphology, proliferation, and transcriptional profile. Over the past couple of decades there have been intense efforts to understand the molecular mechanisms involved, and members of the Ras superfamily of small GTPases have emerged as important players. Mutated versions of the Ras genes were first identified in human cancers some 20 years ago, but more recently, the Rho branch of the family has been receiving increased attention. In addition to the experimental evidence implicating Rho GTPase signaling in promoting malignant transformation, genetic analysis of human cancers has now revealed a few examples of direct alterations in the genes encoding regulators of Rho GTP... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369673 Mon, 22 Jan 2007 16:12:02 +0100 369673 http://www.medworm.com/index.php?rid=369672&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D11885563%26dopt%3DAbstract Authors: Oster SK, Ho CS, Soucie EL, Penn LZ The activated product of the myc oncogene deregulates both cell growth and death check points and, in a permissive environment, rapidly accelerates the affected clone through the carcinogenic process. Advances in understanding the molecular mechanism of Myc action are highlighted in this review. With the revolutionary developments in molecular diagnostic technology, we have witnessed an unprecedented advance in detecting activated myc in its deregulated, oncogenic form in primary human cancers. These improvements provide new opportunities to appreciate the tumor subtypes harboring deregulated Myc expression, to identify the essential cooperating lesions, and to realize the therapeutic potential of targeting Myc. Knowledge of both the breadth... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369672 Mon, 22 Jan 2007 16:12:02 +0100 369672 http://www.medworm.com/index.php?rid=369671&cid=s_34377_6_f&fid=34377&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D12374276%26dopt%3DAbstract Authors: Martin KA, Blenis J Control of translation initiation is an important means by which cells tightly regulate the critical processes of growth and proliferation. Multiple effector proteins contribute to translation initiation of specially modified mRNAs that modulate these processes. Coordinated regulation of these translational effectors by multiple signaling pathways allows the integration of information regarding mitogenic signals, energy levels, and nutrient sufficiency. The mTOR protein, in particular, serves as a sensor of all of these signals and is thought to thus serve as a crucial checkpoint control protein. Signals from the mTOR pathway converge with mitogenic inputs from the phosphoinositide (PI) 3-kinase pathway on translational effector proteins to coordinately con... Advances in Cancer Research journals http://www.medworm.com/rss/comments.php?id=369671 Mon, 22 Jan 2007 16:12:02 +0100 369671