Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Partial hepatectomy (PH) initiates cellular signals for regeneration. Sequential expression of nuclear and cytosolic protooncogenes accompanies the restoration of normal liver function and architecture. Although cirrhosis is known to inhibit liver regeneration, the effects of noncirrhotic cholestasis on hepatocellular proliferation, differentiation, and regulatory gene expression are unknown. To examine this, 25 male Fisher rats underwent common bile duct ligation and division. A 47% +/- 5% PH was performed 10 days after common bile duct ligation and division when histologic analysis revealed cholestasis without cirrhosis. Despite early elevations of total hepatic DNA and RNA values, cholestatic livers demonstrated a significant threefold suppression of expected hepatocyte mitotic indexes 48 and 72 hours after PH, compared with livers after PH alone. Weight restoration in cholestatic livers was 11% +/- 5.2% compared with 40% +/- 4.3% in control livers (+/- SEM; p less than 0.001) 5 days after PH. Analysis of regenerating liver messenger RNA with complementary DNA probes revealed an abnormal, sustained elevation of K-ras expression in cholestatic livers through all time points. Cholestasis blunted but did not obliterate normal sequential elevations in H-ras found in control livers. The expression of c-myc was inhibited threefold with cholestasis 72 hours after PH. These results are the first indication that cholestasis alone inhibits hepatocyte proliferation and the expression of c-myc that normally precedes the first wave of mitosis. This implies that cholestasis without cirrhosis may alter programmed liver gene expression, inhibiting normal hepatic regeneration.
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PMID:Cholestasis without cirrhosis alters regulatory liver gene expression and inhibits hepatic regeneration. 185 28

The mechanisms involved in the proliferative response of the uterus to estrogen are poorly understood. The c-myc proto-oncogene has recently been shown to be rapidly activated in quiescent cells exposed to various mitogens. We have examined expression of c-myc and a closely related proto-oncogene, N-myc, in the rat uterus after in vivo administration of 17beta-estradiol (E2), 5 micrograms/100 g body weight, to prepubertal ovariectomized rats. Maximal c-myc messenger RNA (mRNA) accumulation, as determined by densitometric analysis of Northern blots of poly (A)+ uterine RNA was observed 3 h after E2 treatment. Maximal expression of c-myc was 8.6 +/- 0.8-fold (mean +/- SEM for 3 separate experiments) compared to basal levels seen in vehicle-treated ovariectomized rats. The maximal level of c-myc mRNA in the E2-stimulated uterus was higher (3- to 6-fold) than that observed in uteri from intact rats in either diestrous or the proestrous-estrous stages of the estrous cycle. There was no significant difference in the level of uterine c-myc mRNA throughout the estrous cycle. Under stringent conditions, the N-myc DNA probe hybridized with a single 3 kilobase (kb) transcript which was virtually undetectable in ovariectomized rat uteri and increased 6-fold within 15 min after E2 treatment. Maximal induction was seen 30-60 min post E2 treatment. At 1 h post E2 the level of N-myc mRNA was 9.3 +/- 0.4-fold (n = 3) compared to vehicle-treated rats. Under conditions of slightly reduced stringency, N-myc DNA also hybridized with a 2.2 kilobase transcript. Expression of the N-myc related gene also occurred more rapidly after E2 administration than c-myc mRNA. Our in vivo data are analogous to the in vitro observations that mitogen stimulation of quiescent cells results in a rapid accumulation of myc proto-oncogene mRNAs. In cycling cells in vitro and in the uterus of intact rats throughout the estrous cycle, the level of expression of the myc oncogenes is relatively constant. Since expression of the c-myc and N-myc proto-oncogenes appears to be restricted to different cell and tissue types our data indicate that there is at least one cell type present in the quiescent uterus that is able to respond rapidly to E2. The rapidity of the N-myc response would argue for a direct effect of E2. In contrast the c-myc response is considerably delayed and may be mediated via autocrine, paracrine, or circulating estrogen-dependent growth factors.
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PMID:Estrogen induction of N-myc and c-myc proto-oncogene expression in the rat uterus. 243 92

The effect of GH administration to hypophysectomized rats on expression of the c-myc proto-oncogene and insulin-like growth factor I (IGF-I) in the liver and kidney was examined. In both tissues maximal expression of c-myc occurred by 1 h after a single injection of human GH (100 micrograms/100 g bw). In the liver the maximal c-myc mRNA level was increased 12 +/- 3.9-fold (mean +/- SEM; n = 4), while the maximal c-myc level in the kidney was increased 3.4-fold (n = 2) compared to levels in basal hypophysectomized rats. In both the liver and kidney the IGF-I cDNA hybridized under stringent conditions to three transcripts with apparent sizes of 7.0, 1.8, and diffuse group of transcripts of 0.7-1.1 kilobases. Each of these transcripts demonstrated some degree of GH dependence. Under the hybridization condition used, the 7.0-kilobase IGF-I mRNA was virtually undetectable in the hypophysectomized control rat liver, while the smaller transcripts were easily detectable. Peak expression of each of the IGF-I transcripts occurred 6-12 h after GH administration. Maximal IGF-I expression in the kidney occurred 9 h after the GH injection. To determine whether the increase in c-myc expression following GH could result from a small but undetectable increase in IGF-I expression in these tissues, we administered human recombinant IGF-I to hypophysectomized rats (50 micrograms/100 g bw, ip). Despite a significant increase in serum IGF-I concentrations to levels greater than those present in the first 3 h after GH administration, no increase in c-myc expression was apparent in either the liver or kidney. These observations suggest that GH itself, rather than IGF-I, initiates the mitogenic response in the liver and kidney that follows GH administration to hypophysectomized rats.
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PMID:Growth hormone stimulates sequential induction of c-myc and insulin-like growth factor I expression in vivo. 356 12

Structural alterations and amplifications of the c-myc oncogene have been implicated in the pathogenesis and progression of several human neoplastic diseases. To study the role of c-myc amplification in human hepatocellular carcinomas (HCC), we analyzed 20 HCC using differential polymerase chain reaction (PCR). DNA used for differential PCR was extracted from formalin-fixed, paraffin-embedded tissue obtained by radiographically directed needle aspiration biopsy. Differential PCR reactions included sets of primers for c-myc and a control gene, dopamine D2 receptor (D2R), which yielded products of 150 bp and 110 bp, respectively. Evaluation of amplification was based on the relative concentration of c-myc and D2R PCR products. The c-myc amplification was detected in 10 of 20 HCC. Cases with c-myc amplification tended to have higher histologic grade and were significantly (P = 0.05) associated with worse prognosis. Amplification was present in none of two Grade 1 tumors, seven of the fourteen Grade 2 tumors, and three of four Grade 3 tumors. The mean survival times (+/- SEM) for patients with and without c-myc amplification were 5.7 (+/- 1.8) and 13.8 (+/- 2.6) months, respectively. These results indicate that c-myc amplification in HCC can be evaluated by differential PCR of needle biopsy specimens, and is an unfavorable prognostic indicator.
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PMID:c-myc amplification in hepatocellular carcinoma predicts unfavorable prognosis. 865 26

A number of data suggest that angiotensin II-dependent activation of the protooncogene c-myc participates in the proliferative response of smooth muscle cells (SMC) of rats with spontaneous hypertension (SHR). We therefore investigated the effects of chronic treatment with the angiotensin converting enzyme (ACE) inhibitor quinapril on the oncoprotein c-Myc and the proliferating cell nuclear antigen cyclin A in SMC of small intramyocardial arteries from the left ventricle of SHR. The expression of c-Myc and cyclin A was assessed by immunocytochemical analysis. The number of smooth muscle cells was assessed by morphometrical analysis. As compared to normotensive Wistar-Kyoto (WKY) rats, untreated SHR exhibited an increased percentages of cells expressing c-Myc (33% +/- 4% v 19% +/- 2%, mean +/- SEM, P < .005) and cyclin A (25 +/- 2 v 11% +/- 1%, P < .001). In quinapril-treated SHR compared with untreated SHR, we found decreased expression of c-Myc (22% +/- 2%, P < .005) and cyclin A (13% +/- 1%, P < .001). No significant differences were found between WKY rats and quinapril-treated SHR in the above parameters. Cyclin A was directly correlated with the number of SMCs in each group of rats. These results suggest that an enhanced expression of c-Myc may be involved in the increased proliferation seen in SMCs from small arteries of SHR. Quinapril administration normalizes proliferation in the SMCs of SHR, possibly by inhibiting the expression of the oncoprotein c-Myc and its effects on the cell cycle.
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PMID:Quinapril inhibits c-Myc expression and normalizes smooth muscle cell proliferation in spontaneously hypertensive rats. 937 Mar 86

We completed a multicenter study of the effects of pomegranate cold-pressed (Oil) or supercritical CO(2)-extracted (S) seed oil, fermented juice polyphenols (W), and pericarp polyphenols (P) on human prostate cancer cell xenograft growth in vivo, and/or proliferation, cell cycle distribution, apoptosis, gene expression, and invasion across Matrigel, in vitro. Oil, W, and P each acutely inhibited in vitro proliferation of LNCaP, PC-3, and DU 145 human cancer cell lines. The dose of P required to inhibit cell proliferation of the prostate cancer cell line LNCaP by 50% (ED(50)) was 70 microg/mL, whereas normal prostate epithelial cells (hPrEC) were significantly less affected (ED(50) = 250 g/mL). These effects were mediated by changes in both cell cycle distribution and induction of apoptosis. For example, the androgen-independent cell line DU 145 showed a significant increase from 11% to 22% in G(2)/M cells (P <.05) by treatment with Oil (35 microg/mL) with a modest induction of apoptosis. In other cell lines/treatments, the apoptotic response predominated, for example, in PC-3 cells treated with P, at least partially through a caspase 3-mediated pathway. These cellular effects coincided with rapid changes in mRNA levels of gene targets. Thus, 4-hour treatment of DU 145 cells with Oil (35 microg/mL) resulted in significant 2.3 +/- 0.001-fold (mean +/- SEM) up-regulation of the cyclin-dependent kinase inhibitor p21((waf1/cip1)) (P <.01) and 0.6 +/- 0.14-fold down-regulation of c-myc (P <.05). In parallel, all agents potently suppressed PC-3 invasion through Matrigel, and furthermore P and S demonstrated potent inhibition of PC-3 xenograft growth in athymic mice. Overall, this study demonstrates significant antitumor activity of pomegranate-derived materials against human prostate cancer.
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PMID:Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells. 1538 19

Following our recent report of attractive antibacterial properties of a designed amphiphilic peptide, A(9)K, we have investigated its antitumor activities by examining the modes of its action against different mammalian cell types. The peptide strongly inhibited the growth of cancerous HeLa cells and human promyelocytic leukemia HL60 cells whilst remaining benign to the host cells, including Cos 7 cells, mouse fibroblast NIH3T3 cells and human red blood cells. Images from SEM and fluorescence microscopy showed that A(9)K penetrated HeLa cell membranes and disrupted membrane structures, a feature broadly similar to that observed from its bactericidal actions. Further interactions of A(9)K with inner cellular membranes caused mitochondrial dysfunction associated with the F-actin reorganization and the decreased transcription of bcl-2 and c-myc genes, resulting in HeLa cell apoptosis in a mitochondria-induced apoptosis pathway. Thus A(9)K has high selectivity against cancerous cells and kills them by dual modes of action: membrane disruption and cell apoptosis. In addition, the peptide does not induce non-specific immunological effects and is not degraded by proteases. These features are crucial for developing their applications in future research.
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PMID:Dual modes of antitumor action of an amphiphilic peptide A(9)K. 2335 40

Herein, we present a spectroscopic (CD and UV) and SEM study of a phenylalanine derivative carrying a terminal alkyne moiety and indicated by us CF3IIIPhe, with particular attention to its interaction with Cu(II) cation and some biological macromolecules, as well as a preliminary evaluation of its effect on cancerous cells. CD spectroscopy evidenced the ability of CF3IIIPhe to interact with tel26 and c-myc, two quadruplex DNA (G4 DNA) models explored in this study. Other CD and UV studies revealed the ability of the unnatural amino acid to form aggregates in aqueous solution, to bind Cu(II) cation, and to interact with bovine serum albumin (BSA). Cellular studies demonstrated CF3IIIPhe antiproliferative activity on PC3 cells. Its ability to bind telomeric DNA was verified with tel26 by CD investigation and SEM analysis, that revealed a noteworthy change in DNA morphology (mainly based on nanosphere structures) by CF3IIIPhe, confirming its G4-DNA binding ability already evidenced by spectroscopy.
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PMID:Spectroscopic and SEM evidences for G4-DNA binding by a synthetic alkyne-containing amino acid with anticancer activity. 3192 77