Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0596263 (carcinogenesis)
64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The bcl-2 protein, which protects cells from apoptosis, is normally expressed in a number of adult tissues. Dysregulated bcl-2 expression, secondary to (14;18) chromosomal translocation, seems to promote the development of follicular lymphomas, and recent findings of bcl-2 protein in several solid tumors suggest that it might contribute to the genesis of many other neoplasms. bcl-2 is also highly expressed in normal proliferative endometrium and markedly down-regulated in secretory endometrium, which suggests that its expression is estrogen regulated. Because the development of most endometrial carcinomas is associated with hyperestrogenic states, we began the investigation of the role of bcl-2 in endometrial carcinogenesis by immunohistochemically quantifying its expression in proliferative, hyperplastic, atypically hyperplastic, and carcinomatous endometrium. The results of this study show that bcl-2 is relatively highly expressed in proliferative (n = 11) and hyperplastic (n = 18) endometrium, with respective mean staining scores of 3.59 and 3.47 (scale, 0-4), but is significantly (P < 0.001) down-regulated in atypical hyperplasia (n = 11; score, 0.82), and adenocarcinoma (n = 34; score, 0.86). bcl-2 expression did not correlate with stage, grade, estrogen-receptor, or progesterone-receptor expression. Polymerase chain reaction analyses of DNA isolated from several endometrial carcinomas were negative for (14;18) translocation involving the bcl-2 gene. Thus, bcl-2 apparently plays no role in the progression of atypical hyperplasia to carcinoma or in the development of high-grade or advanced-stage endometrial carcinoma. These results, however, do not rule out the involvement of bcl-2 in very early, preatypical hyperplasia phases of endometrial carcinogenesis. Finally, the marked difference in bcl-2 expression in hyperplastic and atypically hyperplastic glands might prove to be diagnostically useful in the often difficult distinction of these entities.
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PMID:bcl-2 is down-regulated in atypical endometrial hyperplasia and adenocarcinoma. 872 85

Polymerase chain reaction (PCR) and in situ hybridization (ISH) have revolutionized the study of genes and gene expression, and many of these molecular biology advances will greatly impact research in toxicological pathology. PCR is one of the most powerful tools in molecular biology and involves primer-mediated enzymatic in vitro amplification of specific target DNA sequences. Recent innovative methods utilizing PCR technology have been developed to detect mutations in neoplastic and small subpopulations of cells, to study biomarkers of genetic susceptibility and genes involved with carcinogen metabolism, to estimate mutation frequencies, to find novel genes induced by chemical exposure, and to characterize gene expression. ISH provides data on individual cells rather than an average of total cellular populations and allows analysis for heterogeneity. When combined with PCR, the sensitivity of ISH is elevated, and single-copy DNA sequences, single-base mutations, or low copies of messenger RNA (mRNA) can potentially be detected within individual cells. Herein are reviewed ISH- and PCR-based techniques such as single-strand conformation polymorphism analysis to detect point mutations, allelotypic analysis for loss of heterozygosity, differential display of mRNA to characterize gene expression, quantitative reverse transcriptase polymerase chain reaction, and in situ polymerase chain reaction with emphasis on current or potential applications in toxicological pathology. These new and evolving techniques offer tremendous potential in providing new insights into the molecular basis of toxicity and carcinogenesis.
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PMID:Polymerase chain reaction and in situ hybridization: applications in toxicological pathology. 883 77

Previous studies showed that patients with resectable multiploid hepatocellular carcinoma (HCC) had lower overall survival rate and higher recurrent rate than did those with diploid or single aneuploid tumors after hepatic resection. We describe in this study the establishment and characterization of cell lines derived from a single HCC nodule containing multiploid DNA distribution. Two human HCC cell lines, designated HAGS 2.1 and HAGS 2.2, were established by primary culture and single cell cloning methods from a patient with a multiploid HCC tumor. Both cell lines expressed bile canalicular domain-specific antigen of human hepatocyte. The HAGS 2.1 cells were spindle-shaped without prominent intracellular vesicles and had a doubling time of 38 h with DNA ploidy of 4.4 N; cells of HAGS 2.2 were polygonal with many intracellular vesicles and had a doubling time of around 42 h with DNA ploidy of 5.1 N. Hepatitis B surface antigen was detectable in HAGS 2.2 but negative in HAGS 2.1 cells. Both HAGS 2.1 and HAGS 2.2 expressed major histocompatibility complex (MHC) class I antigen, but the former expressed more MHC class II antigen than did the latter. Polymerase chain reaction and subsequent single strain conformation polymorphism analysis disclosed the presence of preS and S regions and the absence of C and X regions of HBV genome in cells of both HAGS 2.1 and HAGS 2.2. We conclude that the establishment of cell lines derived from a single HCC tumor containing multiploid DNA distribution might provide a good in vitro model to study the carcinogenesis and the recurrence mechanism of human hepatocellular carcinoma.
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PMID:Establishment and characterization of two cell lines derived from a single hepatocellular carcinoma containing multiploid DNA distribution. 890 2

The molecular nature of mutations induced by Cd was investigated in this study to elucidate the role of Cd in the initiation of carcinogenesis. Exposing Chinese hamster ovary (CHO)-K1 cells to cadmium acetate markedly decreased the colony-forming ability of cells and induced mutation frequency in the hypoxanthine (guanine) phosphoribosyltransferase (hprt) gene. The mutation frequency induced by Cd at LD30-LD20 doses was approximately 20 times that of untreated cells. D-Mannitol, a scavenger of reactive oxygen species (ROS), significantly protects cells against Cd cytotoxicity and mutagenicity. Furthermore, non-cytotoxic doses of 3-amino-1,2,4-triazole, a catalase inhibitor, potentiates Cd cytotoxicity and mutagenicity. The cellular Cd uptake ability was not altered by the combined treatment with either D-mannitol or 3-amino-1,2,4-triazole. The GSH level and the activities of GSH peroxidase, GSSG reductase, and catalase in cells treated with Cd (4 microM, 4 h) decreased to 78%, 47%, 40%, and 22% of the untreated cells, respectively. Those enzymatic activities recovered to normal levels 8 h after removing Cd. Polymerase chain reaction and DNA sequencing analysis of 54 independent Cd mutants revealed Cd-induced base substitutions, splice mutations, and large genomic deletions. All six types of base substitutions were observed; however, base transversions (22/27; 81%) occurred more frequently than transitions (5/27; 19%). The frequencies of mutations occurring at T.A or G.C base pairs were roughly equal. Results in this study strongly suggest that Cd mutagenicity in CHO-K1 cells is ROS-dependent. Moreover, the unique mutational spectrum induced by Cd implies that specific DNA adducts generated through the interaction of Cd-DNA and ROS may play a role in the mutational specificity.
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PMID:Reactive oxygen species may participate in the mutagenicity and mutational spectrum of cadmium in Chinese hamster ovary-K1 cells. 895 Dec 41

Inactivation of p53 gene products either by mutation or by complex formation with E6 oncoprotein encoded by high risk HPV appears to be a common event in cervical carcinogenesis. This study was designed to clarify this association in 41 primary cervical, 15 endometrial, 3 ovarian and one rectal carcinomas. Polymerase chain reaction analysis revealed presence of high risk HPV in 36 (88%) cervical, 5 (33%) endometrial and none of ovarian and rectal carcinomas. HPV 16 was found in 14 cervical carcinomas, HPV 18 in 19 cervical and 2 endometrial carcinomas and HPV 33 in 28 cervical and 5 endometrial carcinomas. Expression of tumor suppressor protein p53 by using polyclonal antibody CM-1, was detected in 28 (68%) cervical, 7 (47%) endometrial, 2 (66%) ovarian and one (100%) rectal carcinoma. Twenty six cervical and 3 endometrial carcinoma cases were positive for both high risk HPV and p53. We conclude that beside cervical carcinoma HPV infection is not uncommon in endometrial carcinoma and in our experimental design there is no inverse correlation between HPV infection and p53 over-expression in a variety of the tumors analysed in the present study.
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PMID:Infection of human papillomavirus (HPV) and p53 over-expression in human female genital tract carcinoma. 896 6

The many genetic changes associated with human carcinogenesis include the activation and/or inactivation of various genes. Polymerase-chain reaction and single-strand conformation polymorphism analysis [PCR-SSCP] was used to detect alterations at exon 1 of the K-ras gene in 20 lesions of human endometrium. Six cases of endometrial hyperplasia, 13 of endometrial carcinoma and one of endometrial metastasis of ovarian cancer were analyzed. Mutations at exon 1 of the K-ras gene were detected in two of 13 human endometrial carcinoma [15%]; both were histologically defined adenocarcinomas, stage Ib and stage IIa according to the FIGO. Alterations were also observed in the single case of endometrial metastasis of ovarian cancer. It is worthy of note that among the six women with hyperplasic endometrial lesions K-ras gene mutation were not reported. These data suggest that K-ras activation is rare in Polish women and when it does occur it is in cancerous, but not in precancerous, lesions of human endometrium.
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PMID:Detection of K-ras mutations in cancerous lesions of human endometrium. 906 33

We have analysed the DNA from 24 prostate tissue biopsies, spanning a range of Gleason grading from benign to grade 5 and mixed randomly with cervical cancer samples of known human papillomavirus (HPV) status, for the prevalence of HPV DNA, in a double-blind study to ensure complete objectivity. Polymerase chain reactions (PCR) were performed using general E1 open reading frame primers for HPV under low stringency conditions, in addition to reactions containing primers specific for HPV16, E2, and E6 open reading frames under higher, more stringent PCR conditions. The presence of cellular DNA was verified by the use of primers for hypoxanthine guanine phosphoribosyl transferase. DNA bands were not detected in the prostate biopsies using the HPV16-specific primers under high-stringency PCR conditions, however a predominant band in the 400 bp region was observed in 15 of the prostate biopsies using the general primers and the low annealing temperature of 40 degrees C. This fragment was excised and cloned into the pT7 blue vector and the sequence of the insert determined. Although the cloned sequences initiated and terminated with the two authentic PCR primers, they did not contain a significant HPV-related open reading frame. Our results indicate that HPV type 16 and closely related types, as detected by the general primer pair, are unlikely initiators of prostate carcinogenesis within our population.
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PMID:Analysis of prostate tissue DNA for the presence of human papillomavirus by polymerase chain reaction, cloning, and automated sequencing. 913 51

We have investigated loss of heterozygosity of p53 tumor suppressor gene in Indian oral cancer patients, individuals with premalignant leukoplakia lesions, and corresponding normal mucosa, to study the status of p53 alleles in oral cancer pathogenesis. Fifty oral cancers, and 42 oral leukoplakia lesions and corresponding clinically normal oral mucosa from 18 individuals, were analysed. Peripheral blood cells (PBCs) from all the individuals and 47 normal healthy volunteers were also included in the study. Polymerase chain reaction(PCR) of p53 Exon4, followed by restriction enzyme digestion with AccII due to the enzyme polymorphic site at Exon4 codon72, was used to detect homozygosity/heterozygosity of p53 alleles, and compared with the allelic pattern in the corresponding PBC. The PCR product subjected to AccII digestion detected 259 bp, 160/99 bp fragments indicating heterozygosity of p53 alleles in 69% of the 139 individuals. On comparison of the p53 allelic distribution in the lesions or tumour tissues, and corresponding PBC, LOH was observed in 20.5% oral tumors and 22% leukoplakias. However, there was no evidence of LOH in the clinically normal mucosa available from 16 individuals with leukoplakia. Our studies demonstrated LOH of p53 allele in early and advanced stages of oral cancers, as well as leukoplakias, perhaps indicating p53 LOH as one of the early events in oral carcinogenesis. Thus, p53 LOH may be useful as a biomarker in defining a certain population of high risk leukoplakias that may progress to oral cancer.
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PMID:Loss of p53 gene as a biomarker of high risk oral leukoplakias. 942 46

Although inconsistencies exist, some studies have shown that meat consumption is associated with breast cancer risk. Several heterocyclic amines (HAs), formed in the cooking of meats, are mammary carcinogens in laboratory models. HAs are activated by polymorphic N-acetyltransferase (NAT2) and rapid NAT2 activity may increase risk associated with HAs. We investigated whether ingestion of meat, chicken and fish, as well as particular concentrated sources of HAs, was associated with breast cancer risk, and if NAT2 genotype modified risk. Caucasian women with incident breast cancer (n = 740) and community controls (n = 810) were interviewed and administered a food frequency questionnaire. A subset of these women (n = 793) provided a blood sample. Polymerase chain reaction and restriction fragment length polymorphism analyses were used to determine NAT2 genotype. Consumption of red meats, as well as an index of concentrated sources of HAs, was not associated with increased breast cancer risk, nor did risk vary by NAT2 genotype. In post-menopausal women, higher fish consumption was inversely associated with risk (odds ratio = 0.7; 95% confidence interval, 0.4-1.0); among pre-menopausal women, there was the suggestion of inverse associations between risk and pork and chicken intake. Our results suggest that consumption of meats and other concentrated sources of HAs is not associated with increased breast cancer risk. However, due to the strong biologic plausibility for a role of some HAs in mammary carcinogenesis, and the likely measurement error in evaluation of sources of HAs in this study, further studies of these possible relationships are warranted.
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PMID:Breast cancer risk, meat consumption and N-acetyltransferase (NAT2) genetic polymorphisms. 950 25

APC gene mutations play a role in the initiation step of colorectal carcinogenesis in both familial adenomatous polyposis (FAP) and non-FAP patients. Almost all of the APC mutations are nonsense or frameshift mutations, which truncate the APC protein and are thought to inactivate normal APC function. We show a novel method for detecting nonsense and frameshift APC gene mutations by using Saccharomyces cerevisiae. Polymerase chain reaction (PCR)-amplified APC fragments are cloned directly into yeast expression vectors in vivo, and the yeast expresses a hemagglutinin epitope (HA)-tagged APC peptide. When an APC fragment contains a nonsense or frameshift mutation, HA-tagged truncating APC peptide can be detected by Western blotting using an anti-HA antibody. We identified both germ-line and somatic APC mutations in patients with FAP and non-FAP colorectal tumors, respectively. This method, called the yeast-based protein truncation test (YPTT), is simple and fairly cheap, and it can be applied to any genes that are inactivated by protein truncating mutations.
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PMID:Detection of APC mutations by a yeast-based protein truncation test (YPTT). 955 40


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