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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a histochemical study of alkaline phosphatase (ALP) in normal cells of uterine endometrium and endometrial cancer to ascertain the incidence of ALP and the isoenzyme type. For this purpose, cytological specimens and tissue serial sections were subjected to heat-stability and L-phenylalanine (L-p) inhibition test. The Regan-like isoenzyme, a heat-stable and L-p sensitive ALP, which had been thought to derive only from cancer or the placenta, was found in very limited endometrial luminal surface lining cells. Meanwhile ALP activity in endometrial glandular cells was heat and L-p sensitive. Of 42 cases of endometrial cancer, all cases manifested non-specific ALP activity, and 19 cases (45%) manifested heat stability of slight to high degree. 7 endometrial cancers exhibited the Regan-like isoenzyme with marked heat and L-p sensitivity. These findings indicate that in the course of uterine endometrial carcinogenesis, the ALP isoenzyme of endometrial glandular cells undergo a change and that "enzyme deviation" occurs.
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PMID:[Histochemical studies on alkaline phosphatase in normal endometrium and endometrial carcinoma--with a special reference to heat stability and L-phenylalanine inhibition tests (author's transl)]. 730 29

A moderately-differentiated endometrial adenocarcinoma cell line(EI) was established from a surgical specimens obtained from a 55-year-old woman with endometrial carcinoma. This cell line could be transplanted to nude mice, where the cells showed the same histological type as the primary tumor. The doubling time of the cell line was 50.5 hours; the saturation density was 7.5 x 104 cells/cm2; the plating efficiency was 46%. This cell line was determined to produce TPA, but not other tumor markers, such as CA125 or CEA. Neither estrogen receptor, nor progesterone receptor was detected from the culture cell or the primary tumor. Chromosome analysis revealed that cells examined were all 46,XX, + 8,t(14q14q), and only cells with this karyotype were thought to be able to grow. From these results, it was suggested that a gene on No. 8 chromosome would be involved in the carcinogenesis of endometrial adenocarcinoma. Thus this cell line was thought to be useful for the clarification of gene conversion during the process of development of endometrial adenocarcinoma.
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PMID:[Establishment and characterization of the new cell line (EI) from a human endometrial adenocarcinoma]. 766 52

Calphobindin I (CPB I) is a member of the family of Ca(2+)-dependent phospholipid binding proteins collectively termed as annexins. CPB I (Annexin V) has recently been shown to be an endogenous inhibitor of protein kinase C, a key enzyme in the cellular signal transduction and its inhibition by CPB I is presumed to be related ultimately to carcinogenesis. We therefore examined the level of production of CPB I in uterine cancer cells. Immunohistochemical analysis, northern blot, and in situ hybridization showed that the production of CPB I was markedly suppressed at the level of transcription in both cervical and endometrial carcinoma cells when compared to their normal counterparts. Decrease in production of CPB I may lead to dysregulated activation of protein kinase C and, accordingly, may be involved in a disorder of cell differentiation, proliferation, and carcinogenesis.
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PMID:Suppression of calphobindin I (CPB I) production in carcinoma of uterine cervix and endometrium. 767 95

Using data from a case-control study conducted in Northern Italy, we analyzed the relation between alcohol drinking and risk of endometrial cancer. Cases were 726 patients, < 75 years of age, admitted to the Ospedale Maggiore (including the 4 largest teaching and general hospitals in the Greater Milan area), the University Obstetrics and Gynecology Clinics, and the National Cancer Institute of Milan with histologically confirmed endometrial cancer. Controls were 2,123 nonhysterectomized patients, < 75 years of age, admitted for acute nongynecological non-hormone-related nonneoplastic conditions to the same network of hospitals where cases had been identified. When total consumption of all alcoholic beverages was considered, 68.2% of cases and 63.9% of controls were drinkers and 12% of cases and 9.3% of controls reported > or = 2 drinks/day. Considering total alcohol drinking, the relative risk for alcohol drinkers vs. nondrinkers was 1.3 (95% confidence interval 1.1-1.5), and the RR estimates for subsequent levels of intake were 1.1, 1.4, and 1.6 for women drinking > 0 < or = 1, > 1 < or = 2 drinks/day (chi 2(1) trend 11.33, p < 0.001). The estimates were similar when wine only (which represents the large majority of all alcohol intake in Italy) was considered, whereas data were less informative for beer and spirits intake only. No relation emerged between duration of alcohol consumption and risk of endometrial cancer. These findings suggest a potential link between alcohol drinking and endometrial cancer risk and are, in any case, inconsistent with a protective role of alcohol in endometrial carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alcohol and endometrial cancer risk: findings from an Italian case-control study. 773 15

To study the regulation of c-erbB, EFG and TGF-alpha in endometrium, we examined the expression of their mRNA in 5 normal endometrial and 5 endometrial carcinoma tissues by Northern blot and reverse transcription-polymerase chain reaction (RT-PCR). By Northern blot with 10 micrograms of total RNA, c-erbB mRNA was not detected in the normal endometrium, but it was detected in 3 samples of endometrial carcinoma tissues. On the other hand RT-PCR identified c-erbB mRNA in all the normal endometrium and endometrial carcinoma tissues by amplifying cDNA derived from c-erbB mRNA. EGF mRNA was detected by RT-PCR in normal endometrium except in the early follicular phase. It was detected in all cases of endometrial carcinoma tissues. TGF-alpha mRNA was also detected in all the normal and endometrial carcinoma tissues by RT-PCR. Our study suggests that an autocrine/paracrine mechanism of EGF may regulate the endometrial cycle. Because some endometrial carcinoma tissues express the c-erbB mRNA much more than normal endometrium, disruption of the autocrine/paracrine mechanism may trigger subsequent endometrial carcinogenesis.
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PMID:[Expression of epidermal growth factor, transforming growth factor-alpha and epidermal growth factor receptor messenger RNA in human endometrium and endometrial carcinoma]. 777 14

The authors previously reported a significant frequency of activating point mutations in codon 12 and 13 of the K-ras gene in endometrial carcinoma and endometrial atypical hyperplasia from Osaka, Japan. They also showed that alterations of the p53 gene are found frequently in those tumors. This study was designed to reveal possible demographic differences in the prevalence of K-ras and p53 mutations in endometrial carcinoma. Tumor-enriched areas of paraffin-embedded histologic sections obtained through the Colorado Central Cancer Registry were isolated and extracted for DNA. Fragments amplified by polymerase chain reaction (PCR) were screened for transforming mutations in codon 12, 13, or 59-63 of K-ras by direct sequencing. Of 38 endometrial adenocarcinomas that were analyzed, K-ras activation was detected in 4 cases (11%), three in codon 12 (a single case with a GGT-->AGT transition, a single case with a GGT-->GAT transition, and a single case with a GGT-->TGT transversion) and one in codon 13 (a GGC-->GAC mutation). The prevalence of K-ras mutations was significantly lower in endometrial carcinomas from Colorado (4 of 38, 11%) than in those from Osaka, Japan (17 of 57, 31%; P = .02). Mutations in exons 5-8 of p53 were screened by PCR-SSCP analysis, and subsequently confirmed by direct sequencing. Mutations in the p53 gene were detected in 5 of 38 endometrial carcinomas from Colorado (13%), including a single base substitution mutation in 3 cases (60%) and a deletion mutation in 2 cases (40%). Mutations in the p53 gene were significantly more frequently found in G3 cancers (3 of 7, 43%) than G1-G2 cancers combined (2 of 31, 6%; P = .025). Although the prevalence of p53 mutations in endometrial carcinomas from Colorado was not significantly different compared to that from Osaka, Japan (9 of 40, 23%), a G:C-->A:T transition at a CpG site, which was the most common base substitution mutation among Japanese, was not included in any tumors from Colorado. A rare polymorphism in codon 213 (CGA-->CGG) was observed in three cases. These observations may indicate that genetic or environmental factors may significantly influence the pathway of endometrial carcinogenesis.
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PMID:Alteration of the p53 tumor suppressor gene and activation of c-K-ras-2 protooncogene in endometrial adenocarcinoma from Colorado. 785 67

Normal cells in culture generally senesce whereas tumor-derived cells are often, but not without exception, immortal and grow indefinitely. For cells to escape the senescence program, normal genes must be lost or inactivated as shown by somatic cell genetic studies. For example, the introduction of specific chromosomes by microcell-mediated chromosome transfer has been shown to induce senescence of human and rodent tumor cell lines, and the mapping of over ten senescence genes has been achieved by this method. In this study, we observed that two different normal chromosomes induce senescence in the same human endometrial carcinoma cell line, which suggests that multiple pathways to senescence are inactivated in this cell line. This hypothesis has implications for the mechanisms of cellular senescence and its role in carcinogenesis. Furthermore, this hypothesis can explain why not all tumor-derived cells are immortal.
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PMID:Evidence for multiple pathways to cellular senescence. 795 52

Tamoxifen is the major therapeutic agent for the treatment of hormone-dependent breast cancer. Tamoxifen treatment appears to be associated with an increased incidence of endometrial carcinoma in humans and hepatocellular carcinoma in rats. These carcinogenic effects of tamoxifen might be induced by the formation of a tamoxifen reactive intermediate that binds covalently to macromolecules. Liver microsomal cytochrome P450s (CYPs) catalyze the metabolism of tamoxifen, forming a reactive intermediate that binds irreversibly to microsomal proteins, primarily to a 54 kDa protein (Mani, C. and Kupfer, D., Cancer Res., 51, 6052-6058, 1991). The current study identifies the P450 enzymes that catalyze the activation of tamoxifen to a reactive intermediate in rats and humans. Among the species examined, rats, chickens and humans demonstrate low tamoxifen binding activity, ranging from 0.1 to 0.4 nmol bound/mg protein/h. In contrast, hamsters and mice exhibit high binding, 1.2 and 1.6 nmol/mg protein/h respectively. Treatment of male rats with phenobarbital or pregnenolone-16 alpha-carbonitrile (PCN) markedly elevated the binding of tamoxifen to liver microsomal proteins. Methylcholanthrene treatment had no effect on binding. These findings suggested the involvement of CYP3A in catalysis of the covalent binding. Alternate substrates of CYP3A, cortisol and erythromycin, inhibited tamoxifen binding in liver microsomes from PCN- and phenobarbital-treated rats. Treatment of rats with troleandomycin (TAO), an inducer of CYP3A, followed by the dissociation of the TAO-CYP3A complex, elevated the covalent binding to liver microsomes approximately 3-fold. Antibodies against rat CYP3A1 strongly inhibited tamoxifen binding to liver microsomes from PCN- and phenobarbital-treated rats, whereas the antibodies anti-CYP2B1/2B2 did not inhibit binding. In humans, tamoxifen binding was inhibited by the anti-rat CYP3A1 IgG and also by alternate substrates of CYP3A. These results indicate that the activation of tamoxifen to a reactive intermediate by rat and human liver microsomes is principally catalyzed by CYP3A enzymes.
Carcinogenesis 1994 Dec
PMID:Involvement of cytochrome P4503A in catalysis of tamoxifen activation and covalent binding to rat and human liver microsomes. 800 Dec 26

Endometrial carcinoma is theorized to arise from a series of somatic mutations which alter benign endometrium to progressively less differentiated histological lesions. One genetic alteration implicated in the carcinogenesis of endometrial cancer is the mutational activation of the c-Ki-ras oncogene. This study characterizes the frequency and the topographical distribution of activated c-Ki-ras alleles in endometrial carcinoma. Sixty formalin-fixed, paraffin-embedded endometrial cancer specimens were screened for point mutations at codons 12 and 13 of the c-Ki-ras oncogene by polymerase chain reaction and allelic specific oligomer dot-blot hybridization. c-Ki-ras mutations were identified in nine of 60 (15%) tumor specimens. Five cases resulted in G to A transitions, three in G to T transversions, and one in a G to C transversion. These nine mutant tumors were analyzed by selective UV radiation fractionation and polymerase chain reaction for the presence of activated c-Ki-ras alleles in cell populations of various histological phenotype. In eight tumors, c-Ki-ras mutations were uniformly present in the carcinoma cells. One tumor exhibited heterogeneous mutational activation, with mutant c-Ki-ras alleles detected in only grade 2 carcinoma cells but not grade 1 carcinoma cells. c-Ki-ras mutations were present in adjacent hyperplasia with atypia but absent from hyperplasia without atypia. With rare exception, c-Ki-ras activation appears to be an early oncogenic event since it is homogeneously present in premalignant and malignant endometrial tissues.
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PMID:Early mutational activation of the c-Ki-ras oncogene in endometrial carcinoma. 813 66

The triphenylethylene drug tamoxifen is a hepatocarcinogen in rats, has genotoxic potential and may produce carcinoma of the endometrium in humans, while the structurally closely related toremifene has no carcinogenic or genotoxic potential. We have investigated the effects of long-term treatment with tamoxifen and toremifene on the activities of drug metabolizing and antioxidant enzymes in rat liver. Female Sprague-Dawley rats were dosed with equimolar doses of tamoxifen (11.3 and 45 mg/kg) and toremifene (12 and 48 mg/kg) for 12 months and were killed after 2 days, 5 weeks, 3, 6 and 12 months of treatment. After 12 months most rats treated with the high dose of tamoxifen had hyperplastic nodules and hepatocellular carcinomas, while in rats given toremifene or the low dose of tamoxifen, only foci were observed. A striking observation was strong inhibition of the hexose monophosphate shunt (HMS) by tamoxifen and toremifene, which, except in the group given the high dose of tamoxifen, lasted throughout the treatment period. Both antiestrogens induced susceptibility to oxidative stress, as indicated by decreased hepatic contents of reduced glutathione and by increased peroxidation potential of microsomal preparations. The activity of glutathione S-transferase was permanently induced by the high dose of tamoxifen from 5 weeks onwards and was greater in tamoxifen-induced liver tumors than in corresponding macroscopically normal tissue. Similarly, the activity of HMS was elevated by the high dose of tamoxifen at the latest time points, and a further elevation was seen in tamoxifen-induced liver tumors. No such alteration in glutathione S-transferase or HMS activity was seen in animals treated with toremifene or with the low dose of tamoxifen. In conclusion, tamoxifen and toremifene differ markedly with respect to production of liver tumors, and this difference in hepatocarcinogenic potential is reflected in differential effects on glutathione-S-transferase and HMS activities in rat liver.
Carcinogenesis 1994 May
PMID:Alterations of drug metabolizing and antioxidant enzyme activities during tamoxifen-induced hepatocarcinogenesis in the rat. 820 88


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