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)

We developed a new approach for detecting the gene amplification of cancer DNAs with restriction landmark genomic scanning (RLGS). In cancer research, much effort has been made to find the amplified loci of cancer DNAs, because many lines of evidence indicate association between oncogene amplification and carcinogenesis. Conventionally, such gene amplification has been detected by using Southern hybridization with DNA probes. However, only the information of one locus can be obtained by one hybridization procedure, and analysis of many loci throughout the genome is too laborious and time consuming, even if only several candidate genes are investigated. On the other hand, the "in-gel renaturation method" was reported as another alternative for detection of amplified regions. However, even though this method is much improved, it is difficult to detect less than 7-fold amplification, which is often higher than the amplification of many cancer cases. To overcome these limitations and, in addition, to locate the amplified DNA two dimensionally, we applied RLGS for analysis of DNA amplification in cancer tissues, such as breast cancer (infiltrative tubuloadenocarcinoma), neuroblastoma, meningioma (endotheliomatous meningioma), and thyroid cancer (papillary adenocarcinoma). In some cases of breast cancer, several amplified spots located on the same amplicon were detected. In thyroid cancer, in which no amplification has yet been reported, low-grade amplification was also detected. In this report, we demonstrated that RLGS allows us to screen 2000-3000 restriction landmarks distributed on the genome simultaneously, and even low-grade amplification could be detected effectively. Thus, RLGS has proven to be a very useful method in detecting DNA amplification.
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PMID:New approach for detection of amplification in cancer DNA using restriction landmark genomic scanning. 161 37

Newborn F344 rats were treated with polyclonal rabbit anti-thymocyte serum, which caused partial immunosuppression for a limited period. These rats were injected s.c. with cells from human tumor cell lines (two melanomas and a B lymphoma). Within 46 days after the tumor regression a renal carcinosarcoma, resembling Wilms' tumor, developed in each animal, however in male rats an adenocarcinoma of the preputial gland arised. Chromosome analysis and transplantation experiments proved the rat origin of the new tumors. In the present study we describe the biological and morphological characteristics of the adenocarcinoma of the preputial gland (ACPG). Their invasive properties were demonstrated in the lung colony assay, after intra-arterial injection and in the spleen-liver model. ACPG showed unique metastatic phenotype: dependence on the sex of the host.
Carcinogenesis 1992 Jul
PMID:Development and characterization of a sex-dependent metastatic preputial gland adenocarcinoma in human tumor-bearing immunosuppressed F344 rats. 163 99

The effect of dietary benzylselenocyanate (BSC) and its analogue, benzylthiocyanate (BTC), and sodium selenite during the initiation and postinitiation phases of azoxymethane (AOM)-induced intestinal carcinogenesis was studied in male F344 rats. Animals intended for initiation study were fed the high-fat (23.5% corn oil) diets containing 25, 50, and 100 ppm BSC (10, 20, and 40 ppm selenium, respectively) and 100 ppm BTC and 4 ppm selenium (as sodium selenite in drinking water); those intended for postinitiation study were fed the high-fat control diet. Two weeks later, all animals were injected subcutaneously with AOM (15 mg/kg body wt) once weekly for two weeks. Three days after the last AOM injection, animals in the initiation and postinitiation studies were transferred respectively to the high-fat diet and high-fat diets containing BSC and BTC and sodium selenite in drinking water. This regimen was continued until 36 weeks post-AOM injection. BSC inhibited the small intestinal and colon adenocarcinoma incidence and multiplicity of colon adenocarcinomas when fed during the postinitiation phase. Sodium selenite inhibited the incidence and multiplicity of colon adenocarcinomas only during the postinitiation phase. BTC had no inhibitory effect when fed during the initiation and postinitiation phases. The colonic mucosal ornithine decarboxylase activity was significantly inhibited by the administration of all three compounds, BSC (78%), BTC (62%), and sodium selenite (44%). It is concluded that the BSC has an inhibitory effect on the intestinal carcinogenesis in animals fed the high-fat diet.
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PMID:Effect of dietary benzylselenocyanate on azoxymethane-induced colon carcinogenesis in male F344 rats. 164 68

Class-switched monoclonal antibody SV2-61r recognized the extracellular domain of c-erbB-2 protooncogene products separate from the epidermal growth factor receptor. We studied the potential of SV2-61r for evaluating the amplification of c-erbB-2 protooncogene on cancer cells, which has been reported to have prognostic value in adenocarcinoma patients. Radiolabeled SV2-61r specifically bound to various adenocarcinoma cells in addition to c-erbB-2-transfected NIH-3T3 cells (A4) with the affinity constant of 4.4 x 10(8) M-1. SV2-61r injected i.v. localized well to A4 cells xenografted in nude mice. Tumor uptake and localization index of radioiodinated SV2-61r were lower than those of 111In-labeled SV2-61r, probably due to the internalization and dehalogenation of formed antibody-antigen complexes. Biodistribution and specificity of targeting were assessed by comparison among three cells, A4, lung cancer SBC-3 (c-erbB-2 weakly positive) and B-lymphoblastoid Manca cells (c-erbB-2 negative). Tumor:blood ratios, obtained 48 h after injection, were 5.63, 1.45, and 0.68, respectively, indicating the potential of 111In-labeled SV2-61r for evaluating the amplification of c-erbB-2 protooncogene on cancer cells. Because of its close relationship with carcinogenesis and the uniform expression, c-erbB-2 protooncogene products seem to be the optimal target of imaging and therapy of adenocarcinoma patients.
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PMID:Scintigraphic detection of overexpressed c-erbB-2 protooncogene products by a class-switched murine anti-c-erbB-2 protein monoclonal antibody. 167 Oct 1

Barrett's esophagus is a condition in which the stratified squamous epithelium of the esophagus is replaced by metaplastic columnar epithelium that predisposes to the development of esophageal adenocarcinoma. Allelic deletions of 17p and alterations of p53 including elevated p53 protein levels have been observed in many different tumors. To investigate the presence of 17p allelic deletions and p53 protein overexpression in Barrett's adenocarcinomas, we have combined the use of restriction fragment length polymorphism analysis, multiparameter flow cytometry, and DNA content cell sorting. The combined use of these methodologies permits the purification of aneuploid tumor cells for restriction fragment length polymorphism analysis of 17p allelic deletions and the evaluation of p53 protein expression by multiparameter flow cytometry in the same aneuploid tumor cell populations. We analyzed 15 aneuploid populations and one tetraploid populations from 13 Barrett's adenocarcinomas for 17p allelic deletions and p53 protein overexpression to determine whether both of these alterations are involved in carcinogenesis in Barrett's esophagus. Twelve of 13 tumors (92%) had 17p allelic deletions, and 8 of 13 tumors (62%) had p53 protein overexpression. Eight of the 12 tumors (67%) with 17p allelic deletions also had p53 protein overexpression. These data indicate that both 17p allelic deletions and p53 protein overexpression are frequently involved in carcinogenesis in Barrett's esophagus.
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PMID:17p allelic deletions and p53 protein overexpression in Barrett's adenocarcinoma. 168 May 52

A mucin preparation from a colonic adenocarcinoma was used to prepare monoclonal antibodies (MAbs) that reacted specifically either with normal adult small-intestine mucin antigen(s) (SIMA), or normal adult large-intestine mucin antigen(s) (LIMA). Both SIMA and LIMA show a unique oncofetal pattern of expression. Thus SIMA was expressed in early fetal stomach, large and small intestines but thereafter only in the normal small intestine. SIMA expression was detected immunohistochemically in cancers of the colorectum (82/112) and stomach (48/86). LIMA was detected in the stomach of the early fetus but thereafter only in the normal large intestine. LIMA expression was detected in 61/86 cancers of the stomach. Moreover, both SIMA and LIMA were expressed inappropriately in mucosa adjacent to tumors, indicative of the detection of possible pre-malignant epithelium. We used a sandwich ELISA and biochemical procedures to show that the SIMA and LIMA molecules were large extensively glycosylated multi-unit mucin glycoproteins that differed markedly from each other. SIMA, whether extracted from normal small-intestine or colonic cancers, had a molecular weight above 1.000 kDa, a mean buoyant density 1.33 g/ml and s value of 4.8. LIMA had a molecular weight above 10.000 kDa, a mean buoyant density 1.45 g/ml and an s value 9.5. The SIMA and LIMA epitopes were judged to be carbohydrate in nature by reason of their resistance to harsh physical chemical treatments or protease digestion, and sensitivity to periodate oxidation, neuraminidase or beta elimination. Only the SIMA epitope was sensitive to neuraminidase. In conclusion, MAbs to carbohydrate-dependent epitopes on SIMA and LIMA identify the oncofetal pattern of expression of these distinct intestinal mucin glycoproteins in colonic and gastric carcinoma. These MAbs will be useful in further studies of the significance of oncofetal mucin expression during carcinogenesis.
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PMID:Oncofetal expression of the human intestinal mucin glycoprotein antigens in gastrointestinal epithelium defined by monoclonal antibodies. 171 Feb 6

The effects of a high fat diet on progression of minimal cancerous lesions to manifest ones were investigated using a chemo-endocrine carcinogenesis model of rat prostate. Male Fischer 344 rats were alternatively given a diet containing 0.75 ppm of ethinyl estradiol (EE) for 3 weeks and the basal diet without EE for the following 2 weeks, and subcutaneously administered with 3,2'-dimethyl-4-aminobiphenyl (DMAB) at 50 mg/kg body weight 2 days after the diet with EE was changed to the basal one. This sequential treatment was repeated 10 times in 50 weeks, and the animals were fed with either normal fat diet (NF) or high fat diet (HF) during the following 30 weeks. At week 80, all the rats were sacrificed for histological examination of the prostate. Atypical hyperplasia and adenocarcinoma were induced in 15.4% (4/26) and 34.6% (9/26) in the rats fed NF and 44.8% (13/29) and 20.7% (6/29) in those group fed HF, respectively. The incidence of adenocarcinoma was significantly higher in the group fed NF than in the other. However, the number of rats with either atypical hyperplasia or adenocarcinoma was not significantly different between the two groups. These observations provided no supporting evidence that high fat content in diet has enhancing effects on prostatic carcinogenesis. Using different species or strain of rats, C3H/He mice and ACI/Seg rats, additional experiments were also conducted by a slightly modified protocol without changing on fat contents. Although ACI/Seg rats were known to spontaneously develop prostate cancer, the histopathological examinations revealed atypical hyperplasia at 25% (16/64) in mice and microadenocarcinoma at 8.1% (6/74) in rats. Apparently further studies are needed until a more useful and efficient model of prostate carcinogenesis is established.
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PMID:[Promotional effects of high fat diet on chemical carcinogenesis of the prostate]. 171 14

Calcium valproate is an anticonvulsant agent with pharmacokinetic properties similar to sodium valproate and valproic acid. Potential carcinogenesis of calcium valproate was evaluated in B6C3F1 mice and Wistar rats given 125, 250 and 500 mg/kg in the diet for 104 weeks. Survival in treated rats increased in a dose-related pattern despite a tumorigenic response in females. Adenocarcinomas of the uterus and cervix were increased in treated rats when compared to controls. The incidence of uterine neoplasia was 8, 20, 14 and 32% in the control, 125, 250 and 500 mg/kg groups, respectively. Neoplasia in treated rats were detected against a higher than expected background of adenocarcinomas in concurrent controls, since 8% incidence in controls was substantially above the laboratory historical database value of 0.6%. Tumors varied from epithelial masses confined to the endometrium, to transmural, highly desmoplastic neoplasms that invaded the serosa lining and the peritoneal cavity. These tumors metastasized in treated rats but not in controls. The statistically significant (P less than 0.01) increase in uterine adenocarcinomas found in females given 500 mg/kg of calcium valproate contrasts the absence of this tumor type in a previous rat carcinogenicity bioassay with valproic acid. Subcutaneous fibrosarcomas were significantly increased in valproic acid-treated males, but no uterine tumors were reported in females. It is puzzling that a true carcinogenic potential would be expressed by markedly different target organs as obtained with the acid and calcium salt of this moiety.
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PMID:Calcium valproate-induced uterine adenocarcinomas in Wistar rats. 172 66

Colorectal carcinoma was induced in Sprague-Dawley rats by 20-methylcholanthrene. Macroscopical studies revealed that the tumors, either sessile type or semi-pedunculated polyp, were generally observed after 32 weeks of the carcinogen treatment. In the distal colon 46.9% tumors appeared, whereas 20.4% and 32.6% tumors were found in the rectum and proximal colon, respectively. Sequential histopathological studies indicated that hyperplasia of goblet cells was common in early stages, which was reduced thereafter. Carcinogenesis progressed with the appearance of the different grades of dysplasia in colorectal mucosa with first incidence of the severe dysplasia in rats at the 20th week and in situ carcinoma at the close of 28th week. Most of the carcinomas were multifocal in origin and were well differentiated adenocarcinoma with primary invasion at the submucosa. In immunohistological studies, this carcinoma was also reactive with monoclonal antibody 660, prepared against a colorectal carcinoma associated mucin antigen.
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PMID:Induction of colorectal cancer in rats by 20-methylcholanthrene. 173 Jan 42

Two 3 x 3 factorial experiments were conducted to examine the effects of dietary protein (8, 16, and 32% of energy from casein) and dietary fat (12, 24, and 48% of energy from corn oil) on the initiation and promotion of azoxymethane-induced carcinogenesis in rats. For the initiation study, 33 weanling male Sprague-Dawley rats were randomized to each of nine diets fed ad libitum. Azoxymethane was administered s.c. between the fourth to sixth weeks of feeding, providing a total dose of 6 mg/100 g body weight. All rats were subsequently fed a common diet containing 16% energy from protein and 24% energy from fat for an additional 30 to 38 weeks. For the promotion study, all rats were fed a common diet containing 16% of energy from protein and 12% of energy from fat until the completion of azoxymethane administration, when 33 rats were randomized to each of nine diets varying in fat and protein content and fed these diets until sacrifice. Low-protein diets during the initiation phase were associated with increased risk of renal adenocarcinomas (P less than 0.001) and mesenchymal (P = 0.005) malignancies. No other statistically significant relationships were found between the levels of dietary fat or protein and the prevalence of malignant lesions of the small intestine, colon, or kidney in either the initiation or promotion study (although polypoid adenocarcinoma of the colon increased suggestively from 13 to 19 to 26% of rats with increasing dietary protein during initiation). Results of a multiple logistic regression analysis, combining both studies, showed that ad libitum energy intake was significantly associated with intestinal carcinogenesis. The odds of finding an intestinal adenocarcinoma increased by 6.2 +/- 2.6% (SE) for each additional kilocalorie of mean daily ad libitum intake (P = 0.014). The quintile of rats which consumed the least averaged 60 kcal/day, while the most voracious quintile averaged 74 kcal/day. This 14 kcal/day difference in mean ad libitum intake corresponded to more than a doubling (146% increase) of the odds of developing an intestinal adenocarcinoma. These studies suggest that ad libitum energy intake is a critical factor modulating experimental colon carcinogenesis.
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PMID:The combined effects of dietary fat, protein, and energy intake on azoxymethane-induced intestinal and renal carcinogenesis. 173 47


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