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Perspectives on Tissue Interactions in Development and Disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
From the morphogenetic movements of the three germ layers during development to the reactive stromal microenvironment in cancer, tissue interactions are vital to maintaining healthy organ morphologic architecture and function. The stromal compartment is thought to be complicit in tumor progression and, as such, represents an opportune target for disease therapies. However, recent developments in our understanding of the diversity of the stromal compartment and the lack of appropriate models to study its relevance in human disease have limited our further understanding of the role of tissue interactions in tumor progres...
Source: Current Molecular Medicine - September 12, 2009 Category: Molecular Biology Authors: Strand DW, Franco OE, Basanta D, Anderson AR, Hayward SW Tags: Curr Mol Med Source Type: journals

Regulatory Roles of the Ubiquitin-Proteasome System in Cardiomyocyte Apoptosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cardiovascular disease is the leading cause of death in the western world. The major contributor of all cardiovascular deaths is myocardial infarction, which often progresses into end-stage heart failure. The loss of cardiomyocytes is a key problem in the development of cardiovascular disease. Two main processes mediate cardiomyocyte loss: necrosis and apoptosis. In contrast to necrosis, apoptosis is a well regulated process essential in normal development and tissue homeostasis. Tight regulation of this process is crucial, especially in post mitotic cells lacking regenerative capacity, like cardiomyocytes. The ubiquit...
Source: Current Molecular Medicine - September 12, 2009 Category: Molecular Biology Authors: Sohns W, van Veen TA, van der Heyden MA Tags: Curr Mol Med Source Type: journals

Unravelling the Role of Infectious Agents in the Pathogenesis of Human Autoimmunity: The Hypothesis of the Retroviral Involvement Revisited.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The incidence of autoimmune disorders is increasing worldwide. Several theories have been proposed to explain how the breakdown in the balance between autoregulatory immune pathways and pathogenic autoreactivity generate autoimmunity. On the basis of a large body of epidemiological, clinical and experimental evidence, it has been suggested that an unfortunate interplay of genetic susceptibility and environmental factors must play an important role in generating the abnormal autoimmune response. Although genetic factors have been well dissected, the environmental agents, that may be causative of disease are still under ...
Source: Current Molecular Medicine - September 12, 2009 Category: Molecular Biology Authors: Fierabracci A Tags: Curr Mol Med Source Type: journals

Microaerophilic Respiratory Metabolism of Plasmodium falciparum Mitochondrion as a Drug Target.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The Plasmodium falciparum mitochondrion is an organelle that presents structural and physiological characteristics different from mitochondria in other eukaryotes. Moreover, there are substantial differences in the properties of asexual and sexual mitochondria. One of the reasons is the adaptation of the parasite to different environments, in particular the great differences in oxygen tension between the host and the mosquito. In this review, we present a synthesis of the recent data on the ultrastructure, the genome and the physiology of the mitochondrion. We try to clarify the mitochondrial role in the intraerythrocy...
Source: Current Molecular Medicine - September 12, 2009 Category: Molecular Biology Authors: Torrentino-Madamet M, Desplans J, Travaillé C, James Y, Parzy D Tags: Curr Mol Med Source Type: journals

Anabolics in Osteoporosis: The Emerging Therapeutic Tool.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Anabolic therapy for osteoporosis has become the most desirable therapeutic option for menopausal osteoporosis. The anabolic agents currently in clinical use are reviewed. Teriparatide (recombinant human 1-34 parathyroid hormone) is used to treat women with menopausal osteoporosis and men at high risk for fractures. Despite PTH's clinical use, the mechanism underlying its anabolic action requires greater elucidation. Proteol (strontium ranelate) acts by inhibiting bone resorption and presumably promoting bone formation. Though clinical trials have shown that strontium ranelate reduces the frequency of both vertebral an...
Source: Current Molecular Medicine - September 12, 2009 Category: Molecular Biology Authors: Trivedi R, Mithal A, Chattopadhyay N Tags: Curr Mol Med Source Type: journals

Overview of the Molecular Bases of Resistance to Chemotherapy in Liver and Gastrointestinal Tumours.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Primary malignancies of the liver and the gastrointestinal tract constitute one of the main health problems worldwide. Together, these types of tumour are the first cause of death due to cancer, followed by lung and breast cancer respectively. One important limitation in the treatment of these tumours is that, with a few exceptions, they exhibit marked resistance to currently available drugs. Moreover, most of them develop chemoresistance during treatment. The mechanisms responsible for drug refractoriness in gastrointestinal tumours include a reduction in drug uptake; enhanced drug export; intracellular inactivation o...
Source: Current Molecular Medicine - September 12, 2009 Category: Molecular Biology Authors: Marin JJ, Romero MR, Martinez-Becerra P, Herraez E, Briz O Tags: Curr Mol Med Source Type: journals

Medulloblastoma: Role of Developmental Pathways, DNA Repair Signaling, and Other Players.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Medulloblastoma is a cerebellar tumor affecting children and young adults, and accounts for approximately one fifth of all pediatric brain tumors. Despite multimodal therapy that includes surgery, radiotherapy and chemotherapy, recurrence is frequent and overall mortality rate remains relatively high. Moreover, radiation therapy results in severe effects on intellect, and younger age of treatment correlates with larger deficits. Improvements in therapy of this childhood tumor will focus increasingly on the clarification of the exact cellular origin and the genetic mechanisms contributing to tumor formation, and on new ...
Source: Current Molecular Medicine - September 12, 2009 Category: Molecular Biology Authors: Saran A Tags: Curr Mol Med Source Type: journals

Osteopontin: An Effector and an Effect of Tumor Metastasis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Osteopontin (OPN) is a matricellular protein that is produced by multiple tissues in our body and is most abundant in bone. It is also produced by cancer cells and plays a determinative role in the growth, progression and metastasis of cancer. Clinically, OPN has been reported to be upregulated in tumor cells per se; this is also reflected by increased levels of OPN in the circulation. Thus, increased OPN levels the plasma are an effect of tumor growth and progression. Functionally, high OPN levels are determinative of higher incidence of bone metastases in mouse models and are clinically correlated with metastatic bon...
Source: Current Molecular Medicine - September 12, 2009 Category: Molecular Biology Authors: Shevde LA, Das S, Clark DW, Samant RS Tags: Curr Mol Med Source Type: journals

Multiplexed Fluorescence Imaging of Tumor Biomarkers in Gene Expression and Protein Levels for Personalized and Predictive Medicine.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Combining groundbreaking research and developments in cancer biomarkers, nanotechnology and molecular targeted medicine, a new realm of therapy is possible: personalized and predictive medicine. Developing a method to detect the overexpression of several tumor marker genes simultaneously, knowing that a single cell generally expresses more than one altered gene, should have a high predictive value for identifying cancer cells amidst the normal cellular background. Theoretically, a cancer's unique molecular profile can be used to predict its invasive and metastatic potential, its ability to evade immune surveillance, an...
Source: Current Molecular Medicine - September 12, 2009 Category: Molecular Biology Authors: Smith MQ, Staley CA, Kooby DA, Styblo T, Wood WC, Yang L Tags: Curr Mol Med Source Type: journals

Sexual Dimorphism in Autoimmune Disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We briefly survey the concept of autoimmunity and nominate the range of autoimmune diseases that include multisystemic and organ-specific disorders, and cite prevalences of autoimmune diseases in males and females, in humans and in experimental animals. Most human autoimmune diseases such as systemic lupus erythematosus (SLE), multiple sclerosis (MS) and autoimmune thyroid disease, have an increased incidence and prevalence in females, but a few others such as autoimmune diabetes, the Guillain Barré syndrome (GBS) and psoriasis are increased in males. Animal models of autoimmunity show an equivalent sexual dimorph...
Source: Current Molecular Medicine - September 12, 2009 Category: Molecular Biology Authors: McCombe PA, Greer JM, Mackay IR Tags: Curr Mol Med Source Type: journals

Ribosome Inactivating Proteins (RIPs) from Momordica charantia for anti Viral Therapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This review describes the nature and applications of ribosome inactivating proteins (RIPs) from Momordica charantia (bitter melon). RIPs from the plant kingdom have received much attention in biomedical research because they target conserved host protein synthesis machinery and show specificity towards human and animal cell targets. Recent studies aimed at unravelling the enzymatic activities of the M charantia RIPs provide a structural basis for their activities. It has been reported that RIPs are member of the single chain ribosome inactivating protein (SCRIP) family which act irreversibly on ribosome by removing ade...
Source: Current Molecular Medicine - September 12, 2009 Category: Molecular Biology Authors: Puri M, Kaur I, Kanwar RK, Gupta RC, Chauhan A, Kanwar JR Tags: Curr Mol Med Source Type: journals

Diagnostic Approach to Mitochondrial Disorders: the Need for a Reliable Biomarker.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mitochondrial diseases (MD) are disorders caused by impairment of the mitochondrial electron transport chain (ETC). Phenotypes are polymorphous and may range from pure myopathy to multisystemic disorders. The genetic defect can be located on mitochondrial or nuclear DNA. The ETC is needed for oxidative phosphorylation (which provides the cell with the most efficient energetic outcome in terms of ATP production), and consists of five multimeric protein complexes located in the inner mitochondrial membrane. The ETC also requires cytochrome c and a small electron carrier, coenzyme Q10. One of the pathogenic mechanisms of ...
Source: Current Molecular Medicine - September 12, 2009 Category: Molecular Biology Authors: Mancuso M, Orsucci D, Coppedè F, Nesti C, Choub A, Siciliano G Tags: Curr Mol Med Source Type: journals

The Acid Sphingomyelinase/Ceramide Pathway: Biomedical Significance and Mechanisms of Regulation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
One of the most intriguing enzymes of sphingolipid biology is acid sphingomyelinase (ASMase). In a phospholipase C reaction, ASMase catalyzes the cleavage of the phosphocholine head group of sphingomyelin to generate ceramide. Cumulative efforts of various laboratories over the past 40 years have placed ASMase and its product ceramide at the forefront of lipid research. Activation of the ASMase/ceramide pathway is a shared response to an ever growing list of receptor and non receptor mediated forms of cellular stress including: death ligands (TNFalpha, TRAIL, Fas ligand), cytokines (IL-1, IFNgamma), radiation, pathogen...
Source: Current Molecular Medicine - September 12, 2009 Category: Molecular Biology Authors: Zeidan YH, Hannun YA Tags: Curr Mol Med Source Type: journals

Stem Cell and Gene Therapeutic Strategies for the Treatment of Multiple Sclerosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Multiple sclerosis is a disease of the central nervous system that predmoninantly affects young adults. The pathogenic mechanisms are complex, however numerous studies indicate that the disease is initiated by an autoimmune attack on protein targets present in the central nervous system. Given that a dysfunctional immune system perpetuates the pathophysiological mechanisms that characterize this inflammatory disorder, several therapeutic approaches that target immune cells or their secreted mediators have been generated and are currently used clinically. Although these strategies have been partially beneficial to a pro...
Source: Current Molecular Medicine - September 12, 2009 Category: Molecular Biology Authors: Siatskas C, Bernard CC Tags: Curr Mol Med Source Type: journals

Tumor immunology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19689292 [PubMed - in process] (Source: Current Molecular Medicine)
Source: Current Molecular Medicine - July 31, 2009 Category: Molecular Biology Authors: Joshi BH, Puri RK Tags: Curr Mol Med Source Type: journals

The contrasting roles 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 true T cells that serve as a bridge between the innate and adaptive immune system, acting as first responders. They recognize lipid antigens rather than peptides, and respond to these when presented by a non-classical class I MHC molecule, CD1d. NKT cells can play a pathogenic role in asthma or a protective role against several autoimmune diseases, in part based on their cytokine profile. In cancer, they can play opposite roles, contributing to anti-tumor immunity or suppressing it. The protective NKT cells were found to be primarily type I NKT cells defined by use of a semi-invariant T cell receptor invo...
Source: Current Molecular Medicine - July 31, 2009 Category: Molecular Biology Authors: Terabe M, Berzofsky JA Tags: Curr Mol Med Source Type: journals

Cancer Immunotherapy: The Role Regulatory T Cells Play and What Can be Done to Overcome their Inhibitory Effects.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Since multiple lines of experimental and clinical data clearly identified regulatory T cells as an integral part of the immune response, these cells have become a major focus of investigation in tumor immunology. Regulatory T cells are in place to dampen ongoing immune responses and to prevent autoimmunity, but they also have profound effects in blocking therapeutic anti-tumor activity. Therefore regulatory T cells are seen as a major hurdle that must be overcome in order for cancer immunotherapy to reach its therapeutic potential. Regulatory T cells are heterogeneous with sub-populations that exhibit distinct function...
Source: Current Molecular Medicine - July 31, 2009 Category: Molecular Biology Authors: Petrausch U, Poehlein CH, Jensen SM, Twitty C, Thompson JA, Assmann I, Puri S, Lacelle MG, Moudgil T, Maston L, Friedman K, Church S, Cardenas E, Haley DP, Walker EB, Akporiaye E, Weinberg AD, Rosenheim S, Crocenzi TS, Hu HM, Curti BD, Urba WJ, Fox BA Tags: Curr Mol Med Source Type: journals

Synthetic Peptide-based cancer vaccines: lessons learned and hurdles to overcome.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In the vast majority of studies conducted to date, activation of cancer-specific T cell immunity through peptide-based immunization has failed to induce objective tumor regression. This failure is particularly troublesome given that these vaccines often stimulate T cell responses. In this review, we attempt to understand the relative failure of peptide cancer vaccines to achieve clinically meaningful responses. In the first part of the review, we discuss specific hurdles to successful application of synthetic peptide-based vaccines including patient variability and epitope selection. In the second part of this review, ...
Source: Current Molecular Medicine - July 31, 2009 Category: Molecular Biology Authors: Voskens CJ, Strome SE, Sewell DA Tags: Curr Mol Med Source Type: journals

Lymphangiogenesis and anti-tumor immune responses.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Tumor-induced immunosuppression is a fundamental problem in cancer immunotherapy and can occur by a variety of cellular and molecular mechanisms, affecting all arms of the immune system. Tumor-produced or elicited factors have been shown to inhibit antigen-specific immune effector function as well as impairment of the development, recruitment and maturation of dendritic cells (DCs) and T cells. A better understanding of the cross-talk between tumors and tumor-associated DCs and T cells is necessary to develop novel approaches for cancer immunotherapy. The recruitment of DCs to tumors, antigen processing and presentatio...
Source: Current Molecular Medicine - July 31, 2009 Category: Molecular Biology Authors: Varney ML, Singh S, Backora M, Chen Z, Singh RK Tags: Curr Mol Med Source Type: journals

Physiology and therapeutics of vascular endothelial growth factor in tumor immunosuppression.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Vascular endothelial growth factor (VEGF), known as a primary mediator of tumor-induced angiogenesis, is now understood to have a role in tumor-associated immunosuppression. Initially, VEGF was identified to alter the growth and maturation of the immature granulocyte-macrophage progenitors, and more recently it has been noted that it prevents dendritic cell (DC) precursors from developing into mature, antigen-presenting DC. VEGF is associated with recruitment of macrophages to the tumor stroma and VEGF inhibition of myeloid progenitor maturation is associated with the development tumor associated macrophages (TAM) whic...
Source: Current Molecular Medicine - July 31, 2009 Category: Molecular Biology Authors: Johnson B, Osada T, Clay T, Lyerly H, Morse M Tags: Curr Mol Med Source Type: journals

Dendritic Cells and their Receptors in Antitumor Immune Response.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
DCs are recognized as the pivotal group of lymphocytes, which induce a variety of antitumor immune responses. Enduring professional antigen presenting cells, DCs eminence to induce adaptive antitumor immune response was exploited, which showed promising results in DCs-based phased clinical studies. Nevertheless, DCs also influence other immune cells to induce multiple arms of immune system to cure cancer. Recently, direct cytotoxic capacity of DCs has been demonstrated in several studies. Altogether DCs hold a strong link between innate and adaptive immune responses. DCs are known to kill tumor cells, phagocytose immun...
Source: Current Molecular Medicine - July 31, 2009 Category: Molecular Biology Authors: Srivastava RM, Khar A Tags: Curr Mol Med Source Type: journals

Clinical considerations in developing dendritic cell vaccine based immunotherapy protocols in cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Since the first reported clinical trial of Dendritic Cell Vaccine (DCV) in cancer in the mid nineties, few hundred clinical trials have been initiated and it was projected that over 3000 patients would be treated in DCV clinical trials by 2008. Despite extensive data to establish its safety, DCV remains an investigational approach, highlighting the need to undertake more meaningful proof of principle studies and more importantly, well designed and well conducted large efficacy trials. As opposed to phase I and II trials of new chemical entities where pharmacokinetics, maximum tolerated dose, toxicity profile and dose r...
Source: Current Molecular Medicine - July 31, 2009 Category: Molecular Biology Authors: Murthy V, Moiyadi A, Sawant R, Sarin R Tags: Curr Mol Med Source Type: journals

A review of studies on targeting interleukin 4 receptor for central nervous system malignancy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Despite advances in biomedical sciences, the prognosis of patients with brain tumors remains poor. Effective treatment is lacking for these central nervous system (CNS) cancers. Targeted immunotoxins are a new class of therapeutic approaches that have emerged for the treatment of human cancers. In this approach, tumor antigen or cell surface receptor is targeted by a chimeric fusion protein consisting of an antibody or a ligand and a suicidal gene or toxin to kill tumor cells. In that regard, receptors for interleukin (IL)-4 (IL-4R) have been identified to be overexpressed on a variety of human CNS tumor cell lines and...
Source: Current Molecular Medicine - July 31, 2009 Category: Molecular Biology Authors: Puri S, Puri S, Mahapatra AK, Hussain E, Sarkar C, Sinha S, Joshi BH Tags: Curr Mol Med Source Type: journals

The Signaling Function of the IL-13Ralpha2 Receptor in the Development of Gastrointestinal Fibrosis and Cancer Surveillance.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The IL-13Ralpha2 receptor is a high affinity receptor for IL-13 that is used only by IL-13 and is quite distinct from the well known IL-13Ralpha1 receptor that IL-13 shares with IL-4. It was widely considered to be a secreted receptor that is devoid of signaling activity and functional only as a decoy receptor that retarded signaling via IL-13Ralpha1. In recent studies, however, it was shown to be capable of robust signaling that results in production of TGF-beta1 and through the latter cytokine, the induction of fibrosis occuring in various experimental inflammatory states. Thus, in initial studies, IL-13 signaling vi...
Source: Current Molecular Medicine - July 31, 2009 Category: Molecular Biology Authors: Strober W, Kitani A, Fichtner-Feigl S, Fuss IJ Tags: Curr Mol Med Source Type: journals

HLA Associations with Nasopharyngeal Carcinoma.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Several associations have been described between the frequency of human leukocyte antigen (HLA) class I genes in certain populations and the risk of developing nasopharyngeal carcinoma (NPC). Associations between ethnic background and geographic distribution, and relative disease incidence have been reported. Populations in geographical areas at higher risk of developing NPC display HLA distribution patterns different and sometimes opposite from areas of low incidence, whereas populations in areas with intermediate incidence display a totally independent pattern. Two main reasons may explain this association between HL...
Source: Current Molecular Medicine - July 31, 2009 Category: Molecular Biology Authors: Li X, Fasano R, Wang E, Marincola FM Tags: Curr Mol Med Source Type: journals

HPV as a Model for the Development of Prophylactic and Therapeutic Cancer Vaccines.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
HPV has been linked to many human malignancies and, as such, represents a major public health crisis. The understanding of HPV biology, however, has helped tremendously in developing prophylactic vaccines, which should help in decreasing mortality due to HPV infections. Understanding HPV biology has allowed researchers to use the virus as a model for the development of not only prophylactic vaccines, but also therapeutic ones. The advantages of HPV as a model stem from the limited number of proteins encoded by the HPV genome that can be targeted by vaccines, and also from the restricted expression of certain viral prot...
Source: Current Molecular Medicine - July 31, 2009 Category: Molecular Biology Authors: Samara RN, Khleif SN Tags: Curr Mol Med Source Type: journals

The role of toll pathways in viral respiratory disease during early childhood.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Virus-induced respiratory disease accounts for the majority of hospitalizations of young children during the winter months. The major viral causes of lower respiratory tract disease in infants and children are respiratory syncytial virus (RSV), rhinovirus, metapneumovirus (hMPV), parainfluenza virus 3 (PIV-3), and influenza. The primary antiviral mechanism involves the activation of cytotoxic T cells and the clearance of virus-infected epithelial cells, and Toll-like receptors that recognize microbial molecular patterns are thought to initiate and orchestrate the immune response. Here, we review the role of Toll-like r...
Source: Current Molecular Medicine - June 30, 2009 Category: Molecular Biology Authors: Lindemans C, Kimpen J, Bont L Tags: Curr Mol Med Source Type: journals

Heterotrimeric g proteins and apoptosis: intersecting signaling pathways leading to context dependent phenotypes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Apoptosis, a programmed cell death mechanism, is a fundamental process during the normal development and somatic maintenance of all multicellular organisms and thus is highly conserved and tightly regulated through numerous signaling pathways. Apoptosis is of particular clinical importance as its dysregulation contributes significantly to numerous human diseases, primarily through changes in the expression and activation of key apoptotic regulators. Each of the four families of heterotrimeric G proteins (G(s), G(i/o), G(q/11) and G(12/13)) has been implicated in numerous cellular signaling processes, including prolifer...
Source: Current Molecular Medicine - June 30, 2009 Category: Molecular Biology Authors: Yanamadala V, Negoro H, Denker BM Tags: Curr Mol Med Source Type: journals

Function and expression pattern of nonsyndromic deafness genes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hearing loss is the most common sensory disorder, present in 1 of every 500 newborns. To date, 46 genes have been identified that cause nonsyndromic hearing loss, making it an extremely heterogeneous trait. This review provides a comprehensive overview of the inner ear function and expression pattern of these genes. In general, they are involved in hair bundle morphogenesis, form constituents of the extracellular matrix, play a role in cochlear ion homeostasis or serve as transcription factors. During the past few years, our knowledge of genes involved in hair bundle morphogenesis has increased substantially. We give a...
Source: Current Molecular Medicine - June 30, 2009 Category: Molecular Biology Authors: Hilgert N, Smith RJ, Van Camp G Tags: Curr Mol Med Source Type: journals

Role of lipoxins and resolvins as anti-inflammatory and proresolving mediators in colon cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recently, lipoxins (LXs) and resolvins (Rvs) have become the topic of intense interest because of expanding views of their action, particularly in chronic disorders where unresolved inflammation is a key factor leading to colon carcinogenesis. Rvs are biosynthesized from omega-3 fatty acids eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA) via cyclooxygenase-2/lipoxygenase (COX-2/LOX) pathways; Rvs are shown to dramatically reduce dermal inflammation, peritonitis, dendritic cell migration, and interleukin production. This explains that dietary supplementation of omega-3 fatty acids generates potent local endoge...
Source: Current Molecular Medicine - June 30, 2009 Category: Molecular Biology Authors: Janakiram NB, Rao CV Tags: Curr Mol Med Source Type: journals

STAT3 Regulation of Glioblastoma Pathogenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Malignant gliomas are the most common primary brain tumors. Despite efforts to find effective treatments, these tumors remain incurable. The failure of malignant gliomas to respond to conventional cancer therapies may reflect the unique biology of these tumors, underscoring the need for new approaches in their investigation. Recently, progress has been made in characterization of the molecular pathogenesis of glioblastoma using a developmental neurobiological perspective, by exploring the role of signaling pathways that control the differentiation of neural stem cells along the glial lineage. The transcription factor S...
Source: Current Molecular Medicine - June 30, 2009 Category: Molecular Biology Authors: de la Iglesia N, Puram SV, Bonni A Tags: Curr Mol Med Source Type: journals

Genetic and molecular approaches to the immunopathogenesis of multiple sclerosis: an update.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Although the aetiology of MS remains elusive, several genetic approaches have provided clues to the underlying molecular pathogensis. In addition to the well known association to HLA class II alleles, weak but highly significant association to the interleukin-7 receptor and interleukin-2 receptor genes has recently been established. A series of other promising candidate genes identified in large genome screens are under evaluation. The genetic predisposition to MS is so far shown to be mediated by common polymorphisms in genes encoding molecules involved in T cell activation and homeostasis, but only a small proportion...
Source: Current Molecular Medicine - June 30, 2009 Category: Molecular Biology Authors: Holmøy T, Harbo H, Vartdal F, Spurkland A Tags: Curr Mol Med Source Type: journals

Mouse Models to Decipher the PI3K Signaling Network in Human Cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Deregulation of the PI3K pathway is common in human cancer. The basic players in this pathway are the kinases PI3K and AKT and the phosphatase PTEN. This review will summarize some of the key animal models that have helped us understand this signaling network and its contribution to tumorigenesis. Recently, great advances in cancer mouse models have been achieved [1]. While germline deletion often affects the development of the organism and can result in embryonic lethality, conditional knockout mouse models offer the possibility of inducing gene deletion in the adult organism. Another useful strategy involves the inac...
Source: Current Molecular Medicine - June 30, 2009 Category: Molecular Biology Authors: Renner O, Carnero A Tags: Curr Mol Med Source Type: journals

STAT3 as a Central Regulator of Tumor Metastases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Metastasis is a major cause of morbidity and mortality in patients with cancer. The molecular mechanisms that control metastasis are related to alterations in various oncogenes, tumor suppressor genes, metastasis suppressor genes, and growth factors and their receptors. These abnormalities affect the downstream signal transduction pathways involved in the control of cell growth and other malignant properties. One of the most recognized signal transduction pathways involves the signal transducer and activator of transcription 3 (STAT3) protein. STAT3, known to be activated by numerous cytokines, growth factors, and onco...
Source: Current Molecular Medicine - June 30, 2009 Category: Molecular Biology Authors: Devarajan E, Huang S Tags: Curr Mol Med Source Type: journals

Developmental abnormalities and cancer predisposition in neurofibromatosis type 1.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Neurofibromatosis type 1 (NF1) is a developmental and cancer predisposing syndrome resulting from haploinsufficiency or alteration in neurofibromin, a multifunctional protein that acts in various signaling pathways affecting morphogenetic processes and cell proliferation. Neurofibromin deficiency deregulates Ras/Raf/MEK/ERK and Ras/PI3K/AKT/PKB/mTOR signaling networks and intersected pathways including the cAMP-dependent protein kinase A (PKA) and the Rho-cofillin which acts on actin cytoskeleton reorganization, cell motility and adhesion. As the neurofibromin-mediated pathways are associated with biological effects de...
Source: Current Molecular Medicine - June 30, 2009 Category: Molecular Biology Authors: Larizza L, Gervasini C, Natacci F, Riva P Tags: Curr Mol Med Source Type: journals

17 AAG for HSP90 Inhibition in Cancer - From Bench to Bedside.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article serves as an overview of the pre-clinical data and clinical trial data on HSP90 inhibitor 17-AAG in different malignancies. 17-AAG has shown significant anti-tumor activity against a spectrum of cancers in the pre-clinical studies and information from various phases of clinical trials is growing. The potential indication of 17-AGG for the treatment of refractory multiple myeloma now awaits for the results of two phase III studies. More work needs to be done before the broader oncological use of HSP90 inhibitors in the area of defining HSP90 client proteins, understanding the mechanism of HSP90 actions, identif...
Source: Current Molecular Medicine - June 30, 2009 Category: Molecular Biology Authors: Usmani SZ, Bona R, Li Z Tags: Curr Mol Med Source Type: journals

Introduction: the evolving picture of the hypoxic tumour microenvironment.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19519396 [PubMed - in process] (Source: Current Molecular Medicine)
Source: Current Molecular Medicine - April 30, 2009 Category: Molecular Biology Authors: Glazer PM, Bindra RS Tags: Curr Mol Med Source Type: journals

Tumor hypoxia as a modifier of DNA strand break and cross-link repair.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hypoxia is a common characteristic of many solid tumors and is associated with poor prognosis. Cells with low oxygen levels can have altered sensitivity to radiotherapy and chemotherapy secondary to changes in the incidence of DNA single- and double-strand breaks (DNA-ssb, DNA-dsb), DNA base damage, DNA-DNA cross-links and DNA-protein cross-links. Recent evidence also supports that cells exposed to chronic hypoxia have a decreased capacity of DNA-dsb repair. This review will examine the influence of short-term and prolonged hypoxia on the two major pathways of DNA-dsb repair: homologous recombination (HR) and non-homol...
Source: Current Molecular Medicine - April 30, 2009 Category: Molecular Biology Authors: Chan N, Koch CJ, Bristow RG Tags: Curr Mol Med Source Type: journals

ATF4, an ER stress and hypoxia-inducible transcription factor and its potential role in hypoxia tolerance and tumorigenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hypoxia/anoxia promotes tumor aggressiveness and negatively impacts tumor response to therapy. Coordinate regulation of HIF-dependent and HIF-independent pathways has been shown to contribute to cellular adaptation to hypoxic stress, and to couple macromolecular synthesis rates to reduced energy availability. An important component of this type of adaptation is the activation of the endoplasmic reticulum kinase PERK by acute or prolonged hypoxia. Activated PERK subsequently induces phosphorylation of the translation initiation factor eIF2alpha and translational upregulation of the transcription factor ATF4. ATF4 is a b...
Source: Current Molecular Medicine - April 30, 2009 Category: Molecular Biology Authors: Ye J, Koumenis C Tags: Curr Mol Med Source Type: journals

Regulation of autophagy through multiple independent hypoxic signaling pathways.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The poorly developed vasculature in solid human tumors is responsible for a profound level of intra- and inter-tumor heterogeneity in oxygen concentration. High levels of hypoxia are associated with poor patient prognosis due in part to hypoxia-induced changes in cell metabolism, angiogenesis, invasiveness and resistance to therapy. Over the past decade several distinct oxygen sensing pathways that regulate the cellular response to hypoxia have been defined. These include transcriptional and translational responses initiated by oxygen-dependent stabilization of the HIF-1 transcription factor, activation of the unfolded...
Source: Current Molecular Medicine - April 30, 2009 Category: Molecular Biology Authors: Rouschop KM, Wouters BG Tags: Curr Mol Med Source Type: journals

Hypoxic tumor microenvironment and cancer cell differentiation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hypoxia or oxygen deficiency is a salient feature of solid tumors. Hypoxic tumors are often resistant to conventional cancer therapies, and tumor hypoxia correlates with advanced stages of malignancy. Hypoxic tumors appear to be poorly differentiated. Increasing evidence suggests that hypoxia has the potential to inhibit tumor cell differentiation and thus plays a direct role in the maintenance of cancer stem cells. Studies have also shown that hypoxia blocks differentiation of mesenchymal stem/progenitor cells, a potential source of tumor-associated stromal cells. It is therefore likely that hypoxia may have a profoun...
Source: Current Molecular Medicine - April 30, 2009 Category: Molecular Biology Authors: Kim Y, Lin Q, Glazer PM, Yun Z Tags: Curr Mol Med Source Type: journals

Novel imaging provides new insights into mechanisms of oxygen transport in tumors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hypoxia is a common feature of solid tumors, and abnormal tumor oxygen transport is a key factor in the imbalance between tumor oxygen supply and demand. Novel advanced imaging techniques can enable new insights into the complexities of tumor oxygen transport and hypoxia that were not previously known or fully appreciated. In this paper, we document new insights into tumor oxygen transport enabled by spectral imaging of microvascular hemoglobin saturation. PMID: 19519401 [PubMed - in process] (Source: Current Molecular Medicine)
Source: Current Molecular Medicine - April 30, 2009 Category: Molecular Biology Authors: Hardee ME, Dewhirst MW, Agarwal N, Sorg BS Tags: Curr Mol Med Source Type: journals

Hypoxia and radiation therapy: past history, ongoing research, and future promise.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We describe the importance of new technologies for measuring hypoxia in human tumors, which allow assessment of pretreatment tumor oxygen levels and changes in hypoxia over the course of prolonged treatment regimens. These offer the possibility of improving the design of clinical trials and the selection of patients who will benefit from hypoxia-directed therapies, as well as the possibility of facilitating the development of better agents and regimens for use in hypoxia-directed therapy. We also discuss how the improved understanding of the abnormal vascular beds in solid tumors and of the effects of hypoxia and related m...
Source: Current Molecular Medicine - April 30, 2009 Category: Molecular Biology Authors: Rockwell S, Dobrucki IT, Kim EY, Marrison ST, Vu VT Tags: Curr Mol Med Source Type: journals

New perspectives for melanoma immunotherapy: role of IL-12.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Metastatic melanoma is a poor prognosis skin cancer. Since conventional treatments including surgery and chemotherapy often fail, novel therapeutic strategies are needed. In particular, identification of melanoma associated antigen has fostered the progress of both active (vaccines) and adoptive immunotherapy. Some promising results have been obtained, but most melanoma patients are not yet cured possibly because of different immune-escape mechanisms operated by tumor cells. Several studies have addressed the use of interleukin (IL)-12 for melanoma therapy due to its immunoregulatory function and anti-tumor activity me...
Source: Current Molecular Medicine - April 30, 2009 Category: Molecular Biology Authors: Cocco C, Pistoia V, Airoldi I Tags: Curr Mol Med Source Type: journals

FANCJ helicase operates in the Fanconi Anemia DNA repair pathway and the response to replicational stress.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Fanconi anemia (FA) is an autosomal recessive disorder characterized by multiple congenital anomalies, progressive bone marrow failure, and high cancer risk. Cells from FA patients exhibit spontaneous chromosomal instability and hypersensitivity to DNA interstrand cross-linking (ICL) agents. Although the precise mechanistic details of the FA/BRCA pathway of ICL-repair are not well understood, progress has been made in the identification of the FA proteins that are required for the pathway. Among the 13 FA complementation groups from which all the FA genes have been cloned, only a few of the FA proteins are predicted to...
Source: Current Molecular Medicine - April 30, 2009 Category: Molecular Biology Authors: Wu Y, Brosh RM Tags: Curr Mol Med Source Type: journals

Targeting allergic airway diseases by siRNA: an option for the future?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Allergic diseases emerge as a substantial health problem of the 21(st) century. Current therapies including combination therapies of corticosteroids and beta(2)-agonists are highly effective, inexpensive and relatively safe. However, these medicaments only relieve symptoms but are not curing disease. So the challenge has to be to develop new therapeutics which are as effective as present medicaments without any side effects and hopefully even heal the disease. It has become clear over the past years that Th2-cells and their cytokines have an outstanding role in the development of airway hyperresponsiveness, airway infl...
Source: Current Molecular Medicine - April 30, 2009 Category: Molecular Biology Authors: Meinicke H, Darcan Y, Hamelmann E Tags: Curr Mol Med Source Type: journals

The TRAIL to viral pathogenesis: the good, the bad and the ugly.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Since the discovery of Tumor Necrosis Factor-Related Apoptosis Inducing Ligand (TRAIL) in 1995, much has been learned about the protein, its receptors and signaling cascade to induce apoptosis and the regulation of its expression. However, the physiologic role or roles that TRAIL may play in vivo are still being explored. The expression of TRAIL on effector T cells and the ability of TRAIL to induce apoptosis in virally infected cells provided early clues that TRAIL may play an active role in the immune defense against viral infections. However, increasing evidence is emerging that TRAIL may have a dual function in the...
Source: Current Molecular Medicine - April 30, 2009 Category: Molecular Biology Authors: Cummins N, Badley A Tags: Curr Mol Med Source Type: journals

The role of genes involved in neuroplasticity and neurogenesis in the observation of a gene-environment interaction (GxE) in schizophrenia.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Schizophrenia is a multifactorial disease characterized by a high heritability. Several candidate genes have been suggested, with the strongest evidences for genes encoding dystrobrevin binding protein 1 (DTNBP1), neuregulin 1 (NRG1), neuregulin 1 receptor (ERBB4) and disrupted in schizophrenia 1 (DISC1), as well as several neurotrophic factors. These genes are involved in neuronal plasticity and play also a role in adult neurogenesis. Therefore, the genetic basis of schizophrenia could involve different factors more or less specifically required for neuroplasticity, including the synapse maturation, potentiation and p...
Source: Current Molecular Medicine - April 30, 2009 Category: Molecular Biology Authors: Le Strat Y, Ramoz N, Gorwood P Tags: Curr Mol Med Source Type: journals

Neuroinflammation and Neuroprotective Strategies in Acute Ischaemic Stroke - from bench to bedside.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cerebrovascular disease is one of the commonest causes of disability and mortality worldwide. Over the past two decades, a tremendous amount of research has been undertaken into developing effective therapeutic strategies for the treatment of acute stroke. Unfortunately, many neuroprotective agents that have shown successful results in treating animal models of acute stroke have failed to translate into clinical treatments. Only tissue-plasminogen activator (t-PA) is currently licensed for use in the treatment of acute ischaemic stroke. One of the important pathophysiological mechanisms involved during the acute phase ...
Source: Current Molecular Medicine - April 1, 2009 Category: Molecular Biology Authors: Shah IM, Macrae IM, Di Napoli M Tags: Curr Mol Med Source Type: journals

On the origin of epidermal cancers.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The epidermis is the stratified epithelium that covers and protects the body from external damage. This tissue undergoes continuous cell renewal throughout the life of the individual at the expense of a pool of pluripotent cells, some of them lie in a well defined niche in the hair follicle known as the bulge. Epidermal tumours are the most frequent type of cancer in human populations, as a consequence, the development and progression of these tumours have been extensively characterised and a number of mouse models generated. Over the last years several findings suggest that a subset of cells, named cancer stem cells, ...
Source: Current Molecular Medicine - April 1, 2009 Category: Molecular Biology Authors: Lorz C, Segrelles C, Paramio JM Tags: Curr Mol Med Source Type: journals