Search results for "CELL PROLIFERATION"
showing 10 items of 1056 documents
Selective targeting of IRF4 by synthetic microRNA-125b-5p mimics induces anti-multiple myeloma activity in vitro and in vivo
2015
Interferon regulatory factor 4 (IRF4) is an attractive therapeutic target in multiple myeloma (MM). We here report that expression of IRF4 mRNA inversely correlates with microRNA (miR)-125b in MM patients. Moreover, we provide evidence that miR-125b is downregulated in TC2/3 molecular MM subgroups and in established cell lines. Importantly, constitutive expression of miR-125b-5p by lentiviral vectors or transfection with synthetic mimics impaired growth and survival of MM cells and overcame the protective role of bone marrow stromal cells in vitro. Apoptotic and autophagy-associated cell death were triggered in MM cells on miR-125b-5p ectopic expression. Importantly, we found that the anti-…
Promoter methylation of MGMT, MLH1 and RASSF1A tumor suppressor genes in head and neck squamous cell carcinoma: Pharmacological genome demethylation …
2012
Promoter hypermethylation of tumor suppressor genes (TSGs) is a common feature of primary cancer cells. However, to date the somatic epigenetic events that occur in head and neck squamous cell carcinoma (HNSCC) tumorigenesis have not been well-defined. In the present study, we analyzed the promoter methylation status of the genes mutL homolog 1 (MLH1), Ras-association domain family member 1 (RASSF1A) and O-6-methylguanine-DNA methyltransferase (MGMT) in 23 HNSCC samples, three control tissues and one HNSCC cell line (UM-SCC 33) using methylation-specific PCR (MSP). The expression of the three proteins was quantified by semi-quantitative immunohistochemical analysis. The cell line was treate…
Neurogenin 3+ cells contribute to β-cell neogenesis and proliferation in injured adult mouse pancreas
2013
Abstract: We previously showed that injury by partial duct ligation (PDL) in adult mouse pancreas activates Neurogenin 3 (Ngn3)(+) progenitor cells that can differentiate to beta cells ex vivo. Here we evaluate the role of Ngn3(+) cells in beta cell expansion in situ. PDL not only induced doubling of the beta cell volume but also increased the total number of islets. beta cells proliferated without extended delay (the so-called 'refractory' period), their proliferation potential was highest in small islets, and 86% of the beta cell expansion was attributable to proliferation of pre-existing beta cells. At sufficiently high Ngn3 expression level, upto 14% of all beta cells and 40% of small i…
Growth Arrest Specific 1 (Gas1) Gene Overexpression in Liver Reduces the In Vivo Progression of Murine Hepatocellular Carcinoma and Partially Restore…
2015
The prognosis of hepatocellular carcinoma patients is usually poor, the size of tumors being a limiting factor for surgical treatments. Present results suggest that the overexpression of Gas1 (growth arrest specific 1) gene reduces the size, proliferating activity and malignancy of liver tumors. Mice developing diethylnitrosamine-induced hepatocellular carcinoma were subjected to hydrodynamic gene delivery to overexpress Gas1 in liver. This treatment significantly (p < 0.05) reduced the number of large tumors, while the difference in the total number of lesions was not significant. Moreover, the number of carcinoma foci in the liver and the number of lung metastases were reduced. These resu…
Chronic social stress inhibits cell proliferation in the adult medial prefrontal cortex: hemispheric asymmetry and reversal by fluoxetine treatment.
2006
Profound neuroplastic changes have been demonstrated in various limbic structures after chronic stress exposure and antidepressant treatment in animal models of mood disorders. Here, we examined in rats the effect of chronic social stress and concomitant antidepressant treatment on cell proliferation in the medial prefrontal cortex (mPFC). We also examined possible hemispheric differences. Animals were subjected to 5 weeks of daily social defeat by an aggressive conspecific and received concomitant, daily, oral fluoxetine (10 mg/kg) during the last 4 weeks. Bromodeoxyuridine (BrdU) labeling and quantitative stereological techniques were used to evaluate the treatment effects on proliferatio…
MicroRNA signature in various cell types of mouse spermatogenesis: Evidence for stage-specifically expressed miRNA-221, -203 and -34b-5p mediated spe…
2012
Background information Recently, it became apparent that microRNAs (miRNAs) can regulate gene expression post-transcriptionally. Despite the advances in identifying the testis-expressed miRNAs and their role in spermatogenesis, only few data are available showing the spatiotemporal expression of miRNAs during this process. Results To understand how different miRNAs can regulate germ cells differentiation, we generated a transgenic mouse model and purified pure populations of premeiotic (PrM) cells and primary spermatocytes (meiotic cells). We also established spermatogonial stem cell (SSC) culture using relatively simple and robust culture conditions. Comparison of global miRNA expression i…
Control of Cell Migration and Inflammatory Mediators Production by CORM-2 in Osteoarthritic Synoviocytes
2011
Background Osteoarthritis (OA) is the most widespread degenerative joint disease. Inflamed synovial cells contribute to the release of inflammatory and catabolic mediators during OA leading to destruction of articular tissues. We have shown previously that CO-releasing molecules exert anti-inflammatory effects in animal models and OA chondrocytes. We have studied the ability of CORM-2 to modify the migration of human OA synoviocytes and the production of chemokines and other mediators sustaining inflammatory and catabolic processes in the OA joint. Methodology/Principal Findings OA synoviocytes were stimulated with interleukin(IL)-1β in the absence or presence of CORM-2. Migration assay was…
Transcription of the MAT2A gene, coding for methionine adenosyltransferase, is up-regulated by E2F and Sp1 at a chromatin level during proliferation …
2006
Methionine adenosyltransferase (MAT) is an essential enzyme because it catalyzes the formation of S-adenosylmethionine, the main methyl donor. Two MAT-encoding genes (MAT1A, MAT2A) are found in mammals. The latter is expressed in proliferating liver, dedifferentiation and cancer, whereas MAT1A is expressed in adult quiescent hepatocytes. Here, we report studies on the molecular mechanisms controlling the induction of MAT2A in regenerating rat liver and in proliferating hepatocytes. The MAT2A is up-regulated at two discrete moments during liver regeneration, as confirmed by RNApol-ChIP analysis. The first one coincides with hepatocyte priming (i.e. G0-G1 transition), while the second one tak…
Loss of PHD3 allows tumours to overcome hypoxic growth inhibition and sustain proliferation through EGFR
2014
Solid tumours are exposed to microenvironmental factors such as hypoxia that normally inhibit cell growth. However, tumour cells are capable of counteracting these signals through mechanisms that are largely unknown. Here we show that the prolyl hydroxylase PHD3 restrains tumour growth in response to microenvironmental cues through the control of EGFR. PHD3 silencing in human gliomas or genetic deletion in a murine high-grade astrocytoma model markedly promotes tumour growth and the ability of tumours to continue growing under unfavourable conditions. The growth-suppressive function of PHD3 is independent of the established PHD3 targets HIF and NF-κB and its hydroxylase activity. Instead, l…
Differential protective effects of red wine polyphenol extracts (RWEs) on colon carcinogenesis.
2014
Various epidemiological studies have shown that a regular and moderate consumption of red wine is correlated with a decreased relative risk of developing coronary heart disease and cancer. These health benefits are commonly attributed to high contents of polyphenols, particularly resveratrol, representing important sources of antioxidants. However, resveratrol does not seem to be the only bioactive compound present in the wine which contains numerous other polyphenols. The present study investigates the efficiency of red wine extracts (RWEs), containing different polyphenols, on colon cancer cell proliferation in vitro and on colonic aberrant crypt foci (ACF) in vivo. Proliferation, cell cy…