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Chapter 1: Introduction.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Advances in Cancer Research - November 4, 2009 Category: Cancer & Oncology Authors: Bettuzzi S Tags: Adv Cancer Res Source Type: journals

Chapter 2: Clusterin (CLU): From one gene and two transcripts to many proteins.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Advances in Cancer Research - November 4, 2009 Category: Cancer & Oncology Authors: Rizzi F, Coletta M, Bettuzzi S Tags: Adv Cancer Res Source Type: journals

Chapter 3: The shifting balance between CLU forms during tumor progression.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Advances in Cancer Research - November 4, 2009 Category: Cancer & Oncology Authors: Pucci S, Bettuzzi S Tags: Adv Cancer Res Source Type: journals

Chapter 4: Regulation of Clusterin activity by calcium.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Advances in Cancer Research - November 4, 2009 Category: Cancer & Oncology Authors: Pajak B, Orzechowski A Tags: Adv Cancer Res Source Type: journals

Chapter 5: Nuclear CLU (nCLU) and the fate of the cell.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ge...
Source: Advances in Cancer Research - November 4, 2009 Category: Cancer & Oncology Authors: Bettuzzi S, Rizzi F Tags: Adv Cancer Res Source Type: journals

Chapter 6: The chaperone action of Clusterin and its putative role in quality control of extracellular protein folding.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 patholog...
Source: Advances in Cancer Research - November 4, 2009 Category: Cancer & Oncology Authors: Wyatt A, Yerbury J, Poon S, Dabbs R, Wilson M Tags: Adv Cancer Res Source Type: journals

Chapter 7: Cell protective functions of secretory Clusterin (sCLU).Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Advances in Cancer Research - November 4, 2009 Category: Cancer & Oncology Authors: Klock G, Baiersdörfer M, Koch-Brandt C Tags: Adv Cancer Res Source Type: journals

Chapter 8: Clusterin: A multifacet protein at the crossroad of inflammation and autoimmunity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 an...
Source: Advances in Cancer Research - November 4, 2009 Category: Cancer & Oncology Authors: Falgarone G, Chiocchia G Tags: Adv Cancer Res Source Type: journals

Chapter 9: Oxidative stress in malignant progression: The role of Clusterin, a sensitive cellular biosensor of free radicals.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 aforem...
Source: Advances in Cancer Research - November 4, 2009 Category: Cancer & Oncology Authors: Trougakos IP, Gonos ES Tags: Adv Cancer Res Source Type: journals

Clusterin (CLU) and prostate cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 microar...
Source: Advances in Cancer Research - November 4, 2009 Category: Cancer & Oncology Authors: Rizzi F, Bettuzzi S Tags: Adv Cancer Res Source Type: journals

The role of clusterin (CLU) in malignant transformation and drug resistance in breast carcinomas.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Advances in Cancer Research - November 4, 2009 Category: Cancer & Oncology Authors: Redondo M, Tellez T, Roldan MJ Tags: Adv Cancer Res Source Type: journals

CLU and colon cancer. The dual face of CLU: from normal to malignant phenotype.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Advances in Cancer Research - November 4, 2009 Category: Cancer & Oncology Authors: Mazzarelli P, Pucci S, Spagnoli LG Tags: Adv Cancer Res Source Type: journals

Clusterin (CLU) and lung cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Advances in Cancer Research - November 4, 2009 Category: Cancer & Oncology Authors: Panico F, Rizzi F, Fabbri LM, Bettuzzi S, Luppi F Tags: Adv Cancer Res Source Type: journals

Clusterin and chemoresistance.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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, an...
Source: Advances in Cancer Research - November 4, 2009 Category: Cancer & Oncology Authors: Djeu JY, Wei S Tags: Adv Cancer Res Source Type: journals

CLU "in and out": looking for a link.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Advances in Cancer Research - November 4, 2009 Category: Cancer & Oncology Authors: Pucci S, Mazzarelli P, Nucci C, Ricci F, Spagnoli LG Tags: Adv Cancer Res Source Type: journals

Regulation of CLU gene expression by oncogenes and epigenetic factors implications for tumorigenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 unders...
Source: Advances in Cancer Research - November 4, 2009 Category: Cancer & Oncology Authors: Sala A, Bettuzzi S, Pucci S, Chayka O, Dews M, Thomas-Tikhonenko A Tags: Adv Cancer Res Source Type: journals

Conclusions and perspectives.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Advances in Cancer Research - November 4, 2009 Category: Cancer & Oncology Authors: Bettuzzi S Tags: Adv Cancer Res Source Type: journals

The function, proteolytic processing, and histopathology of Met in cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 cl...
Source: Advances in Cancer Research - October 27, 2009 Category: Cancer & Oncology Authors: Hanna JA, Bordeaux J, Rimm DL, Agarwal S Tags: Adv Cancer Res Source Type: journals

Managing tumor angiogenesis lessons from VEGF-resistant tumors and wounds.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 metastasiz...
Source: Advances in Cancer Research - October 27, 2009 Category: Cancer & Oncology Authors: Cuevas I, Boudreau N Tags: Adv Cancer Res Source Type: journals

The TRAIL to targeted therapy of breast cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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,...
Source: Advances in Cancer Research - October 27, 2009 Category: Cancer & Oncology Authors: Rahman M, Pumphrey JG, Lipkowitz S Tags: Adv Cancer Res Source Type: journals

Hepatitis B virus X protein molecular functions and its role in virus life cycle and pathogenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 t...
Source: Advances in Cancer Research - October 27, 2009 Category: Cancer & Oncology Authors: Benhenda S, Cougot D, Buendia MA, Neuveut C Tags: Adv Cancer Res Source Type: journals

Drosophila Myc.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Advances in Cancer Research - October 27, 2009 Category: Cancer & Oncology Authors: Gallant P Tags: Adv Cancer Res Source Type: journals

Oxidative stress and lymphocyte persistence: implications in immunotherapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 sy...
Source: Advances in Cancer Research - September 24, 2009 Category: Cancer & Oncology Authors: Mehrotra S, Mougiakakos D, Johansson CC, Voelkel-Johnson C, Kiessling R Tags: Adv Cancer Res Source Type: journals

Chapter 1 ras signaling and therapies.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Advances in Cancer Research - July 16, 2009 Category: Cancer & Oncology Authors: Young A, Lyons J, Miller AL, Phan VT, Alarcón IR, McCormick F Tags: Adv Cancer Res Source Type: journals

Chapter 2 PI3K/PTEN Signaling in Angiogenesis and Tumorigenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 kin...
Source: Advances in Cancer Research - July 16, 2009 Category: Cancer & Oncology Authors: Jiang BH, Liu LZ Tags: Adv Cancer Res Source Type: journals

Chapter 3 tumor dormancy and metastasis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 la...
Source: Advances in Cancer Research - July 16, 2009 Category: Cancer & Oncology Authors: Hedley BD, Chambers AF Tags: Adv Cancer Res Source Type: journals

Chapter 4 histone demethylases and cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 r...
Source: Advances in Cancer Research - July 16, 2009 Category: Cancer & Oncology Authors: Kampranis SC, Tsichlis PN Tags: Adv Cancer Res Source Type: journals

Chapter 5 Sirtuins and p53.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 sirtuin...
Source: Advances in Cancer Research - July 16, 2009 Category: Cancer & Oncology Authors: Leeuwen I, Lain S Tags: Adv Cancer Res Source Type: journals

Chapter 6 oxidative stress and lymphocyte persistence implications in immunotherapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 sy...
Source: Advances in Cancer Research - July 16, 2009 Category: Cancer & Oncology Authors: Mehrotra S, Mougiakakos D, Christian Johansson C, Voelkel-Johnson C, Kiessling R Tags: Adv Cancer Res Source Type: journals

Adhesion proteins meet receptors: a common theme?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 flexibili...
Source: Advances in Cancer Research - December 11, 2008 Category: Cancer & Oncology Authors: Orian-Rousseau V, Ponta H Tags: Adv Cancer Res Source Type: journals

HIV induced AIDS and related cancers: chronic immune activation and future therapeutic strategies.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Advances in Cancer Research - December 11, 2008 Category: Cancer & Oncology Authors: Cadogan M, Dalgleish AG Tags: Adv Cancer Res Source Type: journals

The cancer cell--leukocyte fusion theory of metastasis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 distributio...
Source: Advances in Cancer Research - December 11, 2008 Category: Cancer & Oncology Authors: Pawelek JM, Chakraborty AK Tags: Adv Cancer Res Source Type: journals

Chapter 1 Contribution of AZAP-Type Arf GAPs to Cancer Cell Migration and Invasion.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Advances in Cancer Research - December 7, 2008 Category: Cancer & Oncology Authors: Ha VL, Luo R, Nie Z, Randazzo PA Tags: Adv Cancer Res Source Type: journals

Chapter 2 Role and Regulation of Human Tumor Suppressor SUFU in Hedgehog Signaling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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. Suppr...
Source: Advances in Cancer Research - December 7, 2008 Category: Cancer & Oncology Authors: Cheng SY, Yue S Tags: Adv Cancer Res Source Type: journals

Chapter 3 FAK Expression Regulation and Therapeutic Potential.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 observe...
Source: Advances in Cancer Research - December 7, 2008 Category: Cancer & Oncology Authors: Li S, Hua ZC Tags: Adv Cancer Res Source Type: journals

Chapter 4 Adhesion Proteins Meet Receptors A Common Theme?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 flexibili...
Source: Advances in Cancer Research - December 7, 2008 Category: Cancer & Oncology Authors: Orian-Rousseau V, Ponta H Tags: Adv Cancer Res Source Type: journals

Chapter 5 The Six Family of Homeobox Genes in Development and Cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 i...
Source: Advances in Cancer Research - December 7, 2008 Category: Cancer & Oncology Authors: Christensen KL, Patrick AN, McCoy EL, Ford HL Tags: Adv Cancer Res Source Type: journals

Chapter 6 Mechanisms Regulating the Susceptibility of Hematopoietic Malignancies to Glucocorticoid-Induced Apoptosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Advances in Cancer Research - December 7, 2008 Category: Cancer & Oncology Authors: Sionov RV, Spokoini R, Kfir-Erenfeld S, Cohen O, Yefenof E Tags: Adv Cancer Res Source Type: journals

Chapter 7 IFN Inducibility of Major Histocompatibility Antigens in Tumors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Advances in Cancer Research - December 7, 2008 Category: Cancer & Oncology Authors: Seliger B, Ruiz-Cabello F, Garrido F Tags: Adv Cancer Res Source Type: journals

Chapter 8 The Role of NKT Cells in Tumor Immunity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 t...
Source: Advances in Cancer Research - December 7, 2008 Category: Cancer & Oncology Authors: Terabe M, Berzofsky JA Tags: Adv Cancer Res Source Type: journals

Chapter 9 HIV Induced AIDS and Related Cancers Chronic Immune Activation and Future Therapeutic Strategies.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Advances in Cancer Research - December 7, 2008 Category: Cancer & Oncology Authors: Cadogan M, Dalgleish AG Tags: Adv Cancer Res Source Type: journals

Chapter 10 The Cancer Cell-Leukocyte Fusion Theory of Metastasis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 distributio...
Source: Advances in Cancer Research - December 7, 2008 Category: Cancer & Oncology Authors: Pawelek JM, Chakraborty AK Tags: Adv Cancer Res Source Type: journals

Advances in Cancer Research: Centennial Volume. Introduction.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 18620090 [PubMed - in process] (Source: Advances in Cancer Research)
Source: Advances in Cancer Research - July 18, 2008 Category: Cancer & Oncology Authors: Klein G, Vande Woude GF Tags: Adv Cancer Res Source Type: journals

Introduction.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 18620090 [PubMed - in process] (Source: Advances in Cancer Research)
Source: Advances in Cancer Research - July 17, 2008 Category: Cancer & Oncology Authors: Woude GV Tags: Adv Cancer Res Source Type: journals

Met-related receptor tyrosine kinase ron in tumor growth and metastasis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ov...
Source: Advances in Cancer Research - July 17, 2008 Category: Cancer & Oncology Authors: Wagh PK, Peace BE, Waltz SE Tags: Adv Cancer Res Source Type: journals

TAM Receptor Tyrosine Kinases: Biologic Functions, Signaling, and Potential Therapeutic Targeting in Human Cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Advances in Cancer Research - July 17, 2008 Category: Cancer & Oncology Authors: Linger RM, Keating AK, Earp HS, Graham DK Tags: Adv Cancer Res Source Type: journals

Epithelial morphogenesis and intestinal cancer: new insights in signaling mechanisms.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Advances in Cancer Research - July 17, 2008 Category: Cancer & Oncology Authors: Fre S, Vignjevic D, Schoumacher M, Duffy SL, Janssen KP, Robine S, Louvard D Tags: Adv Cancer Res Source Type: journals

Molecular mechanisms and therapeutic development of angiogenesis inhibitors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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, de...
Source: Advances in Cancer Research - July 17, 2008 Category: Cancer & Oncology Authors: Cao Y Tags: Adv Cancer Res Source Type: journals

The tumorigenicity of human embryonic stem cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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. Whe...
Source: Advances in Cancer Research - July 17, 2008 Category: Cancer & Oncology Authors: Blum B, Benvenisty N Tags: Adv Cancer Res Source Type: journals

Contact interactions between cells that suppress neoplastic development: can they also explain metastatic dormancy?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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. Althoug...
Source: Advances in Cancer Research - July 17, 2008 Category: Cancer & Oncology Authors: Rubin H Tags: Adv Cancer Res Source Type: journals