Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pancreatic cancer represents the fourth leading cause of cancer death in men and the fifth in women. Prognosis remains dismal, mainly because the diagnosis is made late in the clinical course of the disease. The need to improve the diagnosis, detection, and treatment of pancreatic cancer is great. It is in this type of cancer, in which the mortality is so great and the clinical detection so difficult that the recent advances of molecular biology may have a significant impact. Genetic alterations can be detected at different levels. These alterations include oncogene mutations (most commonly, K-ras mutations, which occur in 75% to more than 95% of pancreatic cancer tissues), tumour suppressor genes alterations (mainly, p53, p16, DCC, etc.), overexpression of growth factors (such as EGF, TGF alpha, TGF beta 1-3, aFGF, bTGF, etc.) and their receptors (i.e., EGF receptor, TGF beta receptor I-III, etc.). Insights into the molecular genetics of pancreatic carcinogenesis are beginning to form a genetic model for pancreatic cancer and its precursors. These improvements in our understanding of the molecular biology of pancreatic cancer are not simply of research interest, but may have clinical implications, such as risk assessment, early diagnosis, treatment, and prognosis evaluation.
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PMID:Molecular biology of pancreatic cancer; oncogenes, tumour suppressor genes, growth factors, and their receptors from a clinical perspective. 1066 Apr 90

Aging enhances apoptosis of hepatocytes under normal physiological conditions and increases the susceptibility to apoptosis of hepatocytes, whereas chronic calorie restriction (CR) suppresses the age-enhanced susceptibility to apoptosis. To clarify the subcellular mechanisms of age-associated dysregulation of apoptosis and the effects of CR, we analyzed the expression of genes promoting apoptosis (p53, Fas receptor, Fas ligand, TNF receptor 1, TNFalpha, Bax, TGF beta 1) and genes preventing apoptosis (Bcl-2 and Bcl-XL) in the livers of 3-, 6-, 15-, and 24-month-old male F344 rats that were either fed ad libitum or subjected to a 30% reduction in food intake (CR). After the age of 6 months, expression of p53, Fas receptor, Fas ligand, and TNFalpha mRNAs was up-regulated with aging. CR suppressed this age-enhanced p53 and Fas receptor mRNA expression, but expression of the other genes was not altered significantly by aging or CR. Expression of Fas receptor in hepatocytes, as detected immunohistochemically, increased with age, but CR suppressed age-accelerated Fas receptor expression. Our findings suggest that TNF ligand/TNF receptor family signaling, particularly Fas receptor expression, is important in age- and CR-modulated apoptosis of hepatocytes. Hepatocytes that were immunoreactive for p53 had slightly increased with aging, suggesting that p53 may mediate the age-enhanced up-regulation of Fas receptor in hepatocytes.
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PMID:Impact of aging and life-long calorie restriction on expression of apoptosis-related genes in male F344 rat liver. 1242 91

It is widely known that patients with idiopathic pulmonary fibrosis (IPF) are frequently associated with lung cancer. Although a complication with lung cancer is an important prognostic factor for IPF, standard treatments for lung cancer cannot be given because of IPF. Especially, the administration of many anticancer agents is limited by a complication with IPF, which is recognized as a risk factor for the development of fatal lung injury in cancer chemotherapy. Epidemiological studies reveal that cigarette smoking and occupational and environmental exposure to toxic substances are common risk factors for both IPF and lung cancer. It has been assumed that metaplasia in fibrous lesions is pathologically a precancerous lesion, but it is necessary to prove several genetic abnormalities in the process of carcinogenesis in order to clarify that. Currently, several genetic abnormalities in IPF, including in p53, K-ras, FHIT and transforming growth factor (TGF)-beta 1 type II receptor, have been reported.
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PMID:[Idiopathic pulmonary fibrosis and lung cancer]. 1261 Aug 69

The aim of the present study was to examine the significance of the p21 expression in gastric cancer. We examined the expression of p53, p21, TGF beta 1 and PCNA in 75 cases of gastric cancer using immunohistochemical examinations and the expression of p21 RNA by in situ hybridization (ISH). The combination of p53 and p21 expression was related to depth of invasion, lymph node metastasis, and stage grouping. The survival curves of the p53 negative-Group and the p21-positive Group were significantly higher than those of the p53-positive and the p21-negative Group, the p53-and-p21-both-positive Group, and the p53-and-p21-both-negative Group (each p < 0.01). The average PCNA Labelling Index (LI) of the p53-negative-and-p21-positive Group was significantly lower than that of either the p53-positive-and-p21-negative Group or the p53-and-p21-both-positive Group or the p53-and-p21-both-negative Group (p < 0.01, p < 0.05, p < 0.05, respectively). All of the p53-and-p21-both-positive cases were TGF beta 1 positive, and the rate of the TGF beta 1 positive cases in the p53-and-p21-both-positive Group was significantly higher than that of the p53-positive-and-p21-negative Group, and than the rate in the p53-and-p21-both-negative Group (each p < 0.01). The survival curves of the cases with expression of p21 RNA were higher than that of cases without p21 RNA (p < 0.05). Many of the p53-positive-and-p21-negative cases were advanced cancer with very poor prognosis, but many of the p53-negative-and-p21-positive cases were early cancer with good prognosis. These results suggest that p21 suppressed synthesis of DNA via PCNA, and TGF beta 1 is a regulation factor for the expression of p21, and that the combination of p53 and p21 expression is concluded to be a useful prognostic marker of gastric carcinoma.
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PMID:The expression of p53, p21 and TGF beta 1 in gastric carcinoma. 1297 Dec 56

Growth inhibition by transforming growth factor (TGF)-beta 1 has been attributed to the induction of cyclin-dependent kinase inhibitors, among which p21/Waf1 plays a major role in many biological contexts. In the present study, two new intracellular mediators for the induction of p21/Waf1 by TGF-beta 1 were identified in a human hepatocellular carcinoma cell line (JHH-5) expressing mutant-type p53. After addition of TGF-beta 1 to JHH-5 cells, a marked increase of the p21/Waf1 expression preceded the inhibition of DNA synthesis. Expression of IFN regulatory factor (IRF)-1, a known transacting factor for p21/Waf1 promoter, was elevated just before or in parallel with the increase of p21/Waf1. Transduction of antisense IRF-1 inhibited the increase in p21/Waf1 in JHH-5 cells treated with TGF-beta 1 and partially released the cells from the growth arrest by TGF-beta 1. Expression of S100C/A11, a member of the Ca(2+)-binding S100 protein family, also markedly increased after addition of TGF-beta 1. S100C/A11 protein was translocated to and accumulated in nuclei of TGF-beta 1-treated JHH-5 cells, where p21/Waf1 was concomitantly accumulated. When a recombinant S100C/A11 protein was introduced into nuclei of JHH-5 cells, DNA synthesis was markedly inhibited in a dose-dependent manner in the absence of TGF-beta 1. Prior transfection of p21/Waf1-targeted small interfering RNA efficiently blocked decrease of DNA synthesis in JHH-5 cells caused by TAT-S100C/A11 or TGF-beta 1 and markedly inhibited expression of p21/Waf1 protein in the cells. These results indicate that IRF-1 and S100C/A11 mediate growth inhibition by TGF-beta 1 via induction of p21/Waf1.
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PMID:Involvement of interferon regulatory factor 1 and S100C/A11 in growth inhibition by transforming growth factor beta 1 in human hepatocellular carcinoma cells. 1520 26

Quinolones (QNs)-induced arthropathy is an important toxic effect in immature animals leading to restriction of their therapeutic use in pediatrics. However, the exact mechanism still remains unclear. Recently, we have demonstrated that ofloxacin, a typical QN, induces apoptosis of alginate microencapsulated juvenile rabbit joint chondrocytes by disturbing the beta 1 integrin functions and inactivating the ERK/MAPK signaling pathway. In this study, we extend our initial observations to further elucidate the mechanism(s) of ofloxacin-induced apoptosis by utilizing specific caspase inhibitors. Pretreatment with both caspase-9-specific inhibitor zLEHD-fmk and caspase-8 inhibitor zIETD-fmk attenuated ofloxacin-induced apoptosis and activation of caspase-3 of chondrocyte in a concentration-dependent manner, as determined by fluorescent dye staining, enzyme activity assay and immunoblotting. Furthermore, the activation of caspase-9, -8 and -3 stimulated by ofloxacin was significantly inhibited in the presence of zIETD-fmk while pretreatment with zLEHD-fmk only blocked the activation of caspase-9 and -3. Ofloxacin also stimulated a concentration-dependent translocation of cytochrome c from mitochondria into the cytosol and a decrease of mitochondrial transmembrane potential, which was completely inhibited by zIETD-fmk. In addition, ofloxacin was found to increase the level of Bax, tBid, p53 in a concentration- and time-dependent manner. Taken together, The current results indicate that the caspase-8-dependent mitochondrial pathway is primarily involved in the ofloxacin-induced apoptosis of microencapsulated juvenile rabbit joint chondrocytes.
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PMID:Ofloxacin induces apoptosis in microencapsulated juvenile rabbit chondrocytes by caspase-8-dependent mitochondrial pathway. 1796 19

Anaplastic thyroid cancer (ATC) is a rare malignancy. While external beam radiation therapy has improved locoregional control, the median survival of approximately 4 months has not changed in more than half a century due to uncontrolled systemic metastases. The objective of this study was to review the literature in order to identify potential new strategies for treating this highly lethal cancer. PubMed searches were the principal source of articles reviewed. The molecular pathogenesis of ATC includes mutations in BRAF, RAS, catenin (cadherin-associated protein), beta 1, PIK3CA, TP53, AXIN1, PTEN, and APC genes, and chromosomal abnormalities are common. Several microarray studies have identified genes and pathways preferentially affected, and dysregulated microRNA profiles differ from differentiated thyroid cancers. Numerous proteins involving transcription factors, signaling pathways, mitosis, proliferation, cell cycle, apoptosis, adhesion, migration, epigenetics, and protein degradation are affected. A variety of agents have been successful in controlling ATC cell growth both in vitro and in nude mice xenografts. While many of these new compounds are in cancer clinical trials, there are few studies being conducted in ATC. With the recent increased knowledge of the many critical genes and proteins affected in ATC, and the extensive array of targeted therapies being developed for cancer patients, there are new opportunities to design clinical trials based upon tumor molecular profiling and preclinical studies of potentially synergistic combinatorial novel therapies.
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PMID:Anaplastic thyroid cancer: molecular pathogenesis and emerging therapies. 1898 68

In vivo selection of phage display libraries have been exploited successfully in the past to isolate various high affinity conformationally strained cyclic peptide ligands (CX(5-7)C, peptides flanked by a cysteine residue on each side) for integrin receptors capable of selectively homing to tumor vasculatures. Previously, such phase display library studies have shown that integrin alpha 5 beta 1 binds with high affinity to cyclic peptides containing CRGDGWC motif. Herein we show that a lipopeptide with just the RGDGW motif (without the flanking cysteine groups) covalently attached to the lysine residue of a monolysinylated cationic amphiphile (RGDGWK-lipopeptide 1) delivers genes to cultured cells preferably via alpha 5 beta 1 integrins. Importantly, remarkable tumor growth inhibition was observed when the electrostatic complex of the RGDGWK-lipopeptide 1 and the anti-cancer p53 gene was intravenously administered in C57BL/6J mice bearing the aggressive B16F10 tumor. Immunohistochemical staining of mice tumor cryosections with vasculature markers combined with monitoring expression of the green fluorescence protein in the same tumor cryosections revealed that the RGDGWK-lipopeptide 1 targets genes to tumor vasculatures. The colocalization of the TUNEL (terminal deoxyuridine triphosphate nick-end labeling, a widely used marker of apoptosis) and VE-cadherin (markers of tumor endothelial cells) positive cells in tumor cryosections support the notion that the remarkable tumor growth inhibition property of the RGDGWK-lipopeptide 1:p53 complex is initiated through apoptosis of the tumor endothelial cells.
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PMID:The use of RGDGWK-lipopeptide to selectively deliver genes to mouse tumor vasculature and its complexation with p53 to inhibit tumor growth. 1988 52

The B-CPAP cell line was obtained from a human differentiated papillary thyroid carcinoma. Previous studies showed that the cells present thyroid characteristics such as thyroglobulin production, phenotypic alterations such as synthesis of human chorionic gonadotropin hormone (HCG), expression of neuron specific enolase (NSE) and protein S100, and also somatic mutations of p53 and K-rns oncogenes. The present data further characterize this cell line and show an overexpression of transforming growth factor (TGF beta 1) and c-met gene product i.e. the receptor for human growth factor (HGF). The relation between the phenotypic and somatic alterations in the process of malignancy are discussed.
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PMID:Production of tgf-Beta and hgf receptor by a differentiated papillary thyroid-carcinoma cell-line (B-cpap) - implication in malignancy. 2155 87

Feed efficiency is a paramount factor for livestock economy. Previous studies had indicated a substantial heritability of several feed efficiency traits. In our study, we investigated the genetic background of residual feed intake, a commonly used parameter of feed efficiency, in a cattle resource population generated from crossing dairy and beef cattle. Starting from a whole genome association analysis, we subsequently performed combined phenotype-metabolome-genome analysis taking a systems biology approach by inferring gene networks based on partial correlation and information theory approaches. Our data about biological processes enriched with genes from the feed efficiency network suggest that genetic variation in feed efficiency is driven by genetic modulation of basic processes relevant to general cellular functions. When looking at the predicted upstream regulators from the feed efficiency network, the Tumor Protein P53 (TP53) and Transforming Growth Factor beta 1 (TGFB1) genes stood out regarding significance of overlap and number of target molecules in the data set. These results further support the hypothesis that TP53 is a major upstream regulator for genetic variation of feed efficiency. Furthermore, our data revealed a significant effect of both, the Non-SMC Condensin I Complex, Subunit G (NCAPG) I442M (rs109570900) and the Growth /differentiation factor 8 (GDF8) Q204X (rs110344317) loci, on residual feed intake and feed conversion. For both loci, the growth promoting allele at the onset of puberty was associated with a negative, but favorable effect on residual feed intake. The elevated energy demand for increased growth triggered by the NCAPG 442M allele is obviously not fully compensated for by an increased efficiency in converting feed into body tissue. As a consequence, the individuals carrying the NCAPG 442M allele had an additional demand for energy uptake that is reflected by the association of the allele with increased daily energy intake as observed in our study.
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PMID:Systems biology analysis merging phenotype, metabolomic and genomic data identifies Non-SMC Condensin I Complex, Subunit G (NCAPG) and cellular maintenance processes as major contributors to genetic variability in bovine feed efficiency. 2587 52


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