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 carcinogenic effects of N-methyl-N-nitrosourea (MNU) in male Syrian golden hamsters were investigated. After single i.p. administration of MNU at doses of 50 mg/kg or 10 mg/kg, or after five fractionated i.p. injections to make a total dose of 50 mg/kg body weight (10 mg x 5), histopathological examinations were performed at the end of 40th week of the experiment. Neoplastic changes were observed in various organs, and lesions in the pancreas, forestomach, and adrenal gland were predominant. In the pancreas, three tumor types were observed: ductal adenocarcinomas, acinar cell carcinomas, and islet cell carcinomas. The incidences of pancreatic ductal carcinomas were 56, 27, and 0% in the single 50-mg, fractionated 50-mg, and single 10-mg groups, respectively. Two islet carcinomas were observed in the single 50-mg group, and an islet carcinoma and an acinar cell carcinoma were also observed in the fractionated 50-mg group. Several miscellaneous neoplastic lesions, including squamous cell papillomas/carcinomas in the forestomach, cortical adenomas in the adrenal glands, and a seminoma in the testis were also observed. These results indicate MNU to be a multipotent carcinogen with the pancreas as a target organ in the Syrian golden hamster under this experimental condition. The observed high induction rate for pancreatic ductal carcinoma suggests that this MNU protocol is a useful candidate model for experimental pancreatic ductal carcinogenesis.
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PMID:Induction of pancreatic tumors in male Syrian golden hamsters by intraperitoneal N-methyl-N-nitrosourea injection. 155 65

K-ras oncogene mutation has been shown to be a frequent event in pancreatic ductal adenocarcinomas induced by the carcinogen N-nitroso-bis(2-oxopropyl)amine in the hamster. The present study examines the mutational status of the K-ras oncogene in lesions that precede the appearance of invasive ductal adenocarcinomas. Syrian golden hamsters (80-100 g) received 12 weekly doses of 15 mg/kg N-nitroso-bis(2-oxopropyl)amine and were serially sacrificed at 8, 12, 14, 16, or 24 weeks following the initiation of treatment. Ten microns-thick sections of formalin-fixed paraffin-embedded pancreas were examined for hyperplasia, papillary hyperplasia, carcinoma in situ, and invasive and metastatic ductal carcinoma. Marked lesions of interest were scraped from the slide, subjected to polymerase chain reaction-mediated amplification of the first exon of the K-ras gene, and probed by oligonucleotide-specific hybridization for mutations at codon either 12 or 13. Of 186 samples assayed, K-ras codon 12 mutations were detected in 26% of hyperplasias, 46% of papillary hyperplasias, 76% of carcinoma in situ, 80% of adenocarcinomas, and 43% of lymph node metastases. Codon 12 mutations were exclusively G to A changes at the second position. Codon 13 mutations were only detected in 9 of 168 samples. These results suggest that K-ras activation is an early event in N-nitroso-bis(2-oxopropyl)amine-induced pancreatic carcinogenesis in the hamster.
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PMID:K-ras mutation is an early event in pancreatic duct carcinogenesis in the Syrian golden hamster. 164 42

A pancreatic cancer cell line, PC-1, was established from a pancreatic ductal carcinoma induced in a hamster by N-nitrosobis(2-oxopropyl)amine (BOP). The cells grew in a monolayer with a doubling time of 38 h, and floated or piled up to form a duct-like structure. Chromosome counts ranged from 42 to 89. Light and electron microscopic studies of PC-1 cells revealed production of conspicuous amounts of amorphous substance. Injection of PC-1 cells into the homologous hamster pancreas resulted in tumor formation, histopathologically indistinguishable from the original primary pancreatic ductal carcinoma. Immunohistochemical expression of blood group-related antigens (BGRAs), A, B, H, Leb, Lex and Ley was observed both in the cells in the culture, and in tumor transplanted into the pancreas. In the culture supernatant, a high titer of blood group A antigen was detected. This cell line may provide a unique tool for studying the mechanism of BGRA synthesis and release in malignant cells.
Carcinogenesis 1989 May
PMID:Establishment of hamster pancreatic ductal carcinoma cell line (PC-1) producing blood group-related antigens. 253 15

As part of a programme to assess the para-endocrine behaviour of human infiltrating ductal breast carcinoma among Chinese women, this study was designed to compare (Mann-Whitney U test) the immunoreactive mammary tumour tissue concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH), human chorionic gonadotrophin (beta-hCG) and prolaction (PRL) at stages I (n = 9), II (n = 12) and III (n = 7) with that of normal breast tissue (n = 8). It was found that with the exception of FSH and beta-hCG in stages I and III significantly elevated concentrations of protein hormones were noted at all stages of malignancy. The possible importance of these findings in multi-stage mammary carcinogenesis is discussed. It is suggested that measurement of LH concentration may provide an endocrine basis to facilitate the diagnosis of tumours to serve as a guide to the biological behaviour of mammary neoplasms.
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PMID:Inappropriate luteinizing hormone concentration in human breast cancer. 299 18

To clarify whether p53 protein expression is involved in multistep carcinogenesis or the progression of mammary ductal carcinoma, we investigated p53 protein expression in 83 invasive ductal carcinomas (IDC), 10 IDC with a predominant intraductal component, 13 non-invasive ductal carcinoma (NIDC), 16 atypical ductal hyperplasia (ADH) and 39 benign epithelial hyperplasia (EH), using immunohistochemistry. Expression of p53 protein was detected in 24 (28.9%) cases of IDC, 5 (50%) cases of IDC with a predominant intraductal component and 1 (7.6%) case of NIDC. No expression was observed in either ADH or EH. In IDC, including cases with a predominant intraductal component, p53 protein expression was associated with a higher histological grade (P < 0.0001) or mitotic index (P < 0.0005). Although overexpression of c-erbB-2 protein has also shown a similar association with these prognostic indicators, expression of p53 protein correlated regardless of the status of c-erbB-2 overexpression. Completely coordinated expression of p53 protein was seen in both intraductal and invasive components. The intraductal component in IDC including cases with a predominant intraductal component which expresses p53 protein had significantly higher histological grade (P < 0.0005) or more comedo-subtypes (P < 0.0001). These results suggested that p53 protein expression occurs at a stage of NIDC with high histological grade or in comedo-subtypes. Its expression is maintained throughout invasion.
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PMID:Expression of p53 protein in benign epithelial hyperplasia, atypical ductal hyperplasia, non-invasive and invasive mammary carcinoma: an immunohistochemical study. 791 68

In breast cancer, inactivating point mutations in the E-cadherin gene are frequently found in invasive lobular carcinoma (ILC) but never in invasive ductal carcinoma (IDC). Lobular carcinoma in situ (LCIS) adjacent to ILC has previously been shown to lack E-cadherin expression, but whether LCIS without adjacent invasive carcinoma also lacks E-cadherin expression and whether the gene mutations present in ILC are already present in LCIS is not known. We report here that E-cadherin expression is absent in six cases of LCIS and present in 150 cases of ductal carcinoma in situ (DCIS), both without an adjacent invasive component. Furthermore, using mutation analysis, we could demonstrate the presence of the same truncating mutations and loss of heterozygosity (LOH) of the wild-type E-cadherin in the LCIS component and in the adjacent ILC. Our results indicate that E-cadherin is a very early target gene in lobular breast carcinogenesis and plays a tumour-suppressive role, additional to the previously suggested invasion-suppressive role.
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PMID:E-cadherin inactivation in lobular carcinoma in situ of the breast: an early event in tumorigenesis. 936 59

Twenty-three cases of ductal carcinoma in situ (DCIS), ten of which had an associated invasive component, were studied for loss of heterozygosity (LOH) of microsatellite markers on chromosome 9p and the results compared with a panel of 20 invasive breast carcinomas. In addition to the gene encoding p16, chromosome 9p is also thought to contain other putative tumour-suppressor genes. If the three panels of breast tumours showed LOH of markers in this region this would suggest that such putative genes were important in breast carcinogenesis. By studying both preinvasive and invasive breast tumours, it should also be possible to gain further information about the relationship between lesions of a different stage and to determine whether DCIS is indeed a precursor of invasive ductal carcinoma. Levels of LOH were low in the invasive-only set of tumours. Surprisingly, considerably higher levels of loss were observed in the tumours with an in situ component. Also, much heterogeneity was observed between different DCIS ducts or invasive tumour and DCIS from the same case.
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PMID:Loss of heterozygosity at chromosome 9p in ductal carcinoma in situ and invasive carcinoma of the breast. 965 59

The importance of epidermal growth factor (EGF) in both normal and malignant mammary gland development are presented in these studies. Initial findings demonstrated that in the absence of ovarian hormones, EGF had a significant proliferative effect on mammary epithelial cells. To determine whether mammary epithelial cells grown with EGF, in the absence of ovarian hormones, could be transformed by N-methyl-N-nitrosourea (MNU), female ovariectomized Lewis rats were implanted with pellets containing EGF for 1 week and then treated with MNU for initiation. Two days after MNU treatment, ovaries were implanted and EGF pellets were removed from all ovariectomized groups in order to promote carcinogenesis. The mammary carcinoma incidence of the EGF-stimulated group (90%) was not significantly different from the intact group (100%). The mammary cancer morphology of EGF-treated carcinomas was either ductal carcinoma or cribriform adenocarcinoma, whereas intact animals developed mainly papillary and occasional cribriform carcinomas. Fifty-eight percent of the carcinomas from the EGF group were ovarian hormone-independent compared with 10% of carcinomas from the intact group. These results demonstrate that EGF-induced proliferation during initiation with MNU was sufficient to induce the transformation of mammary carcinomas in the absence of ovarian hormones. The hormonal dependency of these EGF-induced carcinomas were different compared with MNU-initiated mammary carcinomas in intact rats.
Carcinogenesis 1999 Apr
PMID:Induction of mammary carcinomas by N-methyl-N-nitrosourea in ovariectomized rats treated with epidermal growth factor. 1022 99

Modifying effects of dietary exposure of diallyl disulfide (DAD), aspirin, DL-alpha-difluoromethylomithine (DFMO), beta-naphthoflavone (beta-NF), alpha-naphthoflavone (alpha-NF), indole-3-carbinol (I3C) and protocatechuic acid (PCA) on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary carcinogenesis were examined in two experiments with female rats. For both experiments, PhIP in corn oil at a concentration of 85 mg/kg was given to animals via an intragastric tube for eight doses for an initial 4 weeks, and test chemicals were given in the diet (Experiment 1: DAD, 200 ppm; aspirin, 400 ppm; DFMO, 400 ppm; beta-NF, 1000 ppm; Experiment 2: alpha-NF, 1000 ppm; I3C, 1000 ppm; PCA, 2000 ppm) for an initial 4 weeks. The experiments were terminated after 25 weeks. In Experiment 1, exposure of beta-NF decreased the incidence and multiplicity of total mammary tumors (fibroadenoma, intraductal carcinoma and invasive ductal carcinoma) (P < 0.001 and P < 0.0001), and lowered the incidence of ductal carcinoma (P < 0.0001). DAD lowered the incidence of ductal carcinoma and decreased the multiplicity of the total tumors (P < 0.01 and P < 0.005). Furthermore, aspirin decreased the total tumors (P < 0.05). In Experiment 2, alpha-NF decreased the multiplicity of ductal carcinoma (P < 0.05). These results suggest that alpha-NF, beta-NF, DAD or aspirin could be chemopreventing agents for mammary neoplasia.
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PMID:Chemoprevention of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine-induced mammary carcinogenesis in rats. 1050 3

Mucous cell hyperplasia (MCH) has been considered an important precursor of pancreatic ductal carcinoma based on histological and molecular research, although various K-ras mutations rates are seen among cases with pancreatic carcinoma, chronic pancreatitis and normal pancreas, with a wide range of histological characters. To investigate the premalignant potential of MCH and the multicentricity of pancreatic carcinoma, we analyzed K-ras mutation at codon 12 in carcinoma foci of 82 cases of surgically-resected pancreatic carcinoma [67 solid-type carcinomas (SCs) and 15 ductectatic-type carcinomas (DCs)], as well as in both MCH and carcinoma foci in 42 cases (30 SCs and 12 DCs), using an enriched polymerase chain reaction (PCR)-enzyme linked mini-sequence assay (ELMA). K-ras mutation was recognized in 85% (57/67) of SCs and 73% (11/15) of DCs, and multiple K-ras mutations in 12% (8/67) of SCs and in 20% (3/15) of DCs. Multiple K-ras mutations were also recognized in MCHs in 47% (14/30) of SCs and in 42% (5/12) of DCs. Moreover, the same sequence at K-ras codon 12 in MCH and carcinoma was identified in 76% (32/42) of carcinoma cases and it was more frequently recognized in hyperplasias with histological atypia (51%, 37 of 72 foci) than those without atypia (24%, 16 of 68 foci) (P<0.0007). These results further support the idea of multicentric carcinogenesis and premalignant potential of atypical hyperplasia in the human pancreas, although about half of the hyperplasias around carcinomas were not thought to be direct precursors.
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PMID:Multiple K-ras mutations in hyperplasia and carcinoma in cases of human pancreatic carcinoma. 1054 56


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