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Increased Cell Proliferation (increased + cell_proliferation)
Selected AbstractsTLR2 engagement on CD8 T cells lowers the thresholdfor optimal antigen-induced T cell activationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2006Anne Cottalorda Abstract TLR have a crucial role in the detection of microbial infection in mammals. Until recently, most investigations on TLR have focused on cells of the innate immune system and on the role of TLR in the initiation of antigen-specific responses following recognition of microbial products by APC. Here, we report that murine T cells express TLR1, TLR2, TLR6, TLR7 and TLR9 mRNA. Using CD8 T cells from F5 TCR-transgenic mice, we demonstrate that the lipopeptide Pam3CysSK4 (Pam), a synthetic analog of bacterial and mycoplasmal lipoproteins that recognizes TLR1/2 complex, costimulates antigen-activated T cells. Costimulation with Pam permits an increased cell proliferation and survival associated with a sustained CD25 expression and an enhanced expression of Bcl-xL anti-apoptotic protein. In addition, we show that costimulation with Pam up-regulates IFN-, production but also granzyme,B secretion and cytotoxic activity of antigen-activated T cells, indicating that TLR2 engagement enhances the major effector functions of CD8 T cells. Finally, we demonstrate that TLR2 engagement on T cells lowers the activation threshold for costimulatory signals delivered by APC. [source] FoxO1 , the key for the pathogenesis and therapy of acne?JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 2 2010Bodo C. Melnik Summary Five main factors play a pivotal role in the pathogenesis of acne: androgen dependence, follicular retention hyperkeratosis, increased sebaceous lipogenesis, increased colonization with P. acnes, and inflammatory events. This paper offers a solution for the pathogenesis of acne and explains all major pathogenic factors at the genomic level by a relative deficiency of the nuclear transcription factor FoxO1. Nuclear FoxO1 suppresses androgen receptor, other important nuclear receptors and key genes of cell proliferation, lipid biosynthesis and inflammatory cytokines. Elevated growth factors during puberty and persistent growth factor signals due to Western life style stimulate the export of FoxO1 out of the nucleus into the cytoplasm via activation of the phos-phoinositide-3-kinase (PI3K)/Akt pathway. By this mechanism, genes and nuclear receptors involved in acne are derepressed leading to increased androgen receptor-mediated signal transduction, increased cell proliferation of androgen-dependent cells, induction of sebaceous lipogenesis and upregulation of Toll-like-receptor-2-dependent inflammatory cytokines. All known acne-inducing factors exert their action by reduction of nuclear FoxO1 levels. In contrast, retinoids, antibiotics and dietary intervention will increase the nuclear content of FoxO1, thereby normalizing increased transcription of genes involved in acne. Various receptor-mediated growth factor signals are integrated at the level of PI3K/Akt activation which finally results in nuclear FoxO1 deficiency. [source] Cell proliferation and death in the brain of active and hibernating frogsJOURNAL OF ANATOMY, Issue 2 2009Silvia Cerri Abstract ,Binomial' cell proliferation and cell death have been studied in only a few non-mammalian vertebrates, such as fish. We thought it of interest to map cell proliferation/apoptosis in the brain of the frog (Rana esculenta L.) as this animal species undergoes, during the annual cycle, physiological events that could be associated with central nervous system damage. Therefore, we compared the active period and the deep underground hibernation of the frog. Using western blot analysis for proliferating cell nuclear antigen (PCNA), we revealed a positive 36 kDa band in all samples and found higher optical density values in the hibernating frogs than in active frogs. In both active and hibernating frogs, we found regional differences in PCNA-immunoreactive cells and terminal transferase dUTP nick-end labelling apoptotic cells in the ventricular zones and parenchyma areas of the main encephalon subdivisions. During the active period of the frogs, the highest concentration of PCNA-immunoreactive cells was found in the ventricle dorsal zone of the cerebral hemispheres but only some of the cells were apoptotic. By contrast, the tectal and cerebellar ventricular zones had a small or medium amount of PCNA-immunoreactive cells, respectively, and a higher number of apoptotic cells. During hibernation, an increased PCNA-immunoreactive cell number was observed in both the brain ventricles and parenchyma compared with active frogs. This increase was primarily evident in the lateral ventricles, a region known to be a proliferation ,hot spot'. Although differences existed among the brain areas, a general increase of apoptotic cell death was found in hibernating frogs, with the highest number of apoptotic cells being detected in the parenchyma of the cerebral hemispheres and optic tectum. In particular, the increased number of apoptotic cells in the hibernating frogs compared with active frogs in the parenchyma of these brain areas occurred when cell proliferation was higher in the corresponding ventricular zones. We suggest that the high number of dying cells found in the parenchymal regions of hibernating frogs might provide the stimulus for the ventricular zones to proliferate. Hibernating frogs could utilize an increased cell proliferation in the brain areas as a neuroprotective strategy to face cell death and the onset of neurological damages. Therefore, the hibernator promises to be a valuable model for studying the mechanisms naturally carried out by the central nervous system in order to adapt itself or survive adverse conditions. [source] All in the family: Using inherited cancer syndromes to understand de-regulated cell signaling in brain tumorsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2007S. Sean Houshmandi Abstract The cell signaling pathways that are tightly regulated during development are often co-opted by cancer cells to allow them to escape from the constraints that normally limit cell growth and cell movement. In this regard, de-regulated signaling in cancer cells confers a number of key tumor-associated properties, including increased cell proliferation, decreased cell death, and increased cell motility. The identification of some of these critical signaling pathways in the nervous system has come from studies of inherited cancer syndromes in which affected individuals develop brain tumors. The study of brain tumors arising in patients with neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and tuberous sclerosis complex (TSC) has already uncovered several key intracellular signaling pathways important for modulating brain tumor growth. An in-depth analysis of these intracellular signaling pathways will not only lead to an improved understanding of the process of brain tumorigenesis, but may also provide important molecular targets for future therapeutic drug design. J. Cell. Biochem. 102: 811,819, 2007. © 2007 Wiley-Liss, Inc. [source] Activation of Src-family tyrosine kinases in hyperproliferative epidermal disordersJOURNAL OF CUTANEOUS PATHOLOGY, Issue 3 2008Elias E. Ayli Background:, Src-family tyrosine kinases (SFKs) are important regulators of keratinocyte growth and differentiation. In a broad range of cell types, persistent activation of SFKs correlates with increased cell proliferation. In this study, we determined if SFK activity is increased in cutaneous neoplasia and psoriasis, common hyperproliferative epidermal disorders. Methods:, Formalin-fixed tissue sections of unremarkable epidermis, psoriasis, actinic keratoses (AKs), squamous cell carcinoma in situ (SCIS) and squamous cell carcinoma (SCC) were subjected to immunohistochemical staining for activated SFKs. Results:, All psoriasis specimens displayed significantly greater staining for activated SFKs than sections of unremarkable skin. In the psoriasis biopsies, the degree of epidermal hyperplasia was proportional to the level of activated SFK staining. All AKs, SCISs and SCCs exhibited more prominent staining than sections of unremarkable epidermis. No discernable difference in activated SFK staining was seen between AKs, SCIS and SCC specimens. Conclusions:, This study shows increased staining of activated SFKs in human biopsy specimens of psoriasis and cutaneous neoplasia. These data provide direct evidence for increased activation of SFKs in the pathogenesis of hyperproliferative epidermal disorders. [source] Proliferative and apoptotic differences between alveolar rhabdomyosarcoma subtypes: A comparative study of tumors containing PAX3-FKHR or PAX7-FKHR gene fusionsPEDIATRIC BLOOD & CANCER, Issue 2 2001Margaret H. Collins MD Abstract Background Most alveolar rhabdomyosarcomas (ARMS) have chromosome translocations and resultant gene fusion products. The more common translocation fuses the PAX3 and FKHR genes; patients who have PAX3-FKHR-positive ARMS have reduced event-free survival compared to patients with ARMS containing the less common translocation that fuses the PAX7 and FKHR genes. Procedure We examined histology, immunohistochemical markers of differentiation, and cell cycle characteristics of a panel of ARMS containing either PAX3-FKHR or PAX7-FKHR transcript to determine if these features differ between the ARMS subsets. Results Cell cycle parameters varied significantly: the number of nuclei that stained with either an immunohistochemical marker of proliferation (MIB1), or a TUNEL-based assay for apoptosis was significantly greater in tumors that expressed PAX3-FKHR compared to tumors that expressed PAX7-FKHR transcript. Conclusions We conclude that compared to PAX7-FKHR-containing tumors, ARMS that contain PAX3-FKHR transcript have (1) increased cell proliferation, consistent with greater loss of cell cycle regulation, and (2) apoptosis that is increased but insufficient to prevent tumor formation. More marked cell cycle dysregulation may contribute to poorer prognosis for patients with ARMS that have PAX3-FKHR fusion. Med Pediatr Oncol 2001;37:83,89. © 2001 Wiley-Liss, Inc. [source] Tumour growth following portal branch ligation in an experimental model of liver metastases,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 6 2010O. Kollmar Background: Portal branch ligation (PBL) is being used increasingly before hepatectomy for colorectal metastases. This study evaluated the effect of PBL on angiogenesis, growth factor expression and tumour growth in a mouse model of hepatic colorectal metastases. Methods: CT26.WT cells were implanted into the left liver lobe of BALB/c mice. Animals underwent PBL of the left liver lobe or sham treatment. Angiogenesis, microcirculation, growth factor expression, cell proliferation and tumour growth were studied over 14 and 21 days by intravital multifluorescence microscopy, laser Doppler flowmetry, immunohistochemistry and western blotting. Results: Left hilar blood flow and tumour microcirculation were significantly diminished during the first 7 days after PBL. This resulted in tumour volume being 20 per cent less than in sham controls by day 14. Subsequently, PBL-treated animals demonstrated recovery of left hilar blood flow and increased expression of hepatocyte growth factor and transforming growth factor ,, associated with increased cell proliferation and acceleration of growth by day 21. Conclusion: PBL initially reduced vascular perfusion and tumour growth, but this was followed by increased growth factor expression and cell proliferation. This resulted in delayed acceleration of tumour growth, which might explain the stimulated tumour growth observed occasionally after PBL. Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Hypoxia and low-nutrition double stress induces aggressiveness in a murine model of melanomaCANCER SCIENCE, Issue 5 2009Tsuyoshi Osawa Antiangiogenic therapy is a potent cancer treatment, however, the possibility of recurrence and resistance to this approach remains. Here we show that hypoxia and low-nutrition double-deprivation stress induces reversible tumor aggressiveness. In a stress-cycle-dependent manner, murine melanoma cells showed morphological changes, up-regulated phospho-Akt, and abnormal regulation of multiple genes including fibroblast growth factor-21, a metabolic regulator, resulting in increased cell proliferation in vitro, and increased tumorigenesis and invasive potential in vivo. In this system, altered cellular metabolism participates in the adaptation of tumor to the double-deprivation stress. Our results suggest the targeting of a minor population of cancer cells resistant to both hypoxia and low nutrition to be an effective new antitumor strategy in combination with antiangiogenic therapy. (Cancer Sci 2009; 100: 844,851) [source] Novel role for polycystin-1 in modulating cell proliferation through calcium oscillations in kidney cellsCELL PROLIFERATION, Issue 3 2008G. Aguiari Objectives: Polycystin-1 (PC1), a signalling receptor regulating Ca2+ -permeable cation channels, is mutated in autosomal dominant polycystic kidney disease, which is typically characterized by increased cell proliferation. However, the precise mechanisms by which PC1 functions on Ca2+ homeostasis, signalling and cell proliferation remain unclear. Here, we investigated the possible role of PC1 as a modulator of non-capacitative Ca2+ entry (NCCE) and Ca2+ oscillations, with downstream effects on cell proliferation. Results and discussion: By employing RNA interference, we show that depletion of endogenous PC1 in HEK293 cells leads to an increase in serum-induced Ca2+ oscillations, triggering nuclear factor of activated T cell activation and leading to cell cycle progression. Consistently, Ca2+ oscillations and cell proliferation are increased in PC1-mutated kidney cystic cell lines, but both abnormal features are reduced in cells that exogenously express PC1. Notably, blockers of the NCCE pathway, but not of the CCE, blunt abnormal oscillation and cell proliferation. Our study therefore provides the first demonstration that PC1 modulates Ca2+ oscillations and a molecular mechanism to explain the association between abnormal Ca2+ homeostasis and cell proliferation in autosomal dominant polycystic kidney disease. [source] | ||||||||||||||||||||||