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

Establishment and its characteristics of a nude mice solid tumor model NHG-1 from human glioma cell line are reported. 5-8 week old NC nude mice of both sexes and SHG-44 cell line used in this experiment were from our laboratory. The initial successful transplantation rate was 7/11 (64%) and that of 30 passages in the subsequent 4 years was 100%. After subcutaneous inoculation, growth curve showed a latent period in week 1-2, slow growing period in week 3-4, rapid growing period in week 5-6 and a final plateau period in week 7. The doubling time was 7 days and cell cycle time was 2.5 days. The cells in G1, S and G2M phases comprised 56%, 27% and 17%, respectively. The survival time of the host was 54 +/- 15 days. The tumor tissues showed a tendency towards invading the surrounding soft tissues. By morphological observation with light and electron microscopes, LDH isozyme assay, PAP immuno-histochemistry labelling GFAP and chromosome analysis, it is confirmed that the transplantable tumor possesses the characteristics of human malignant glioma. The estrogen receptor in the transplantable tumors demonstrated by cytochemical assay indicates that the glioma carcinogenesis is related to endocrine factor of the host. The therapeutic effects of anticancer drugs, such as ACNU, BCNU and 10-hydroxy-2-decenoic acid from the royal jelly on NHG-1 model are evaluated.
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PMID:[Establishment of human glioma cell line--nude mice solid tumor model NHG-1 and its characteristics]. 367 17

Estrogens are important etiologic agents for most gynecologic malignancies, and chronic exposure to estrogen that is unopposed by progestins conveys the greatest risk. Treatments with estrogen facilitate the process of malignant transformation in rodents, but relatively few studies of estrogen-induced carcinogenesis have been performed using human cells. Most malignancies in estrogen-responsive tissues arise from epithelial cells, but an increasing body of evidence emphasizes the role of stromal cells as mediators of the effects of estrogens on epithelial cells. Our studies were designed to assess estrogens as carcinogens for human endometrial stromal cells and to provide a basis for studies of the role of stroma in estrogen-induced carcinogenesis in humans. Acute treatments with the estrogens diethylstilbestrol (DES), 17 beta-estradiol (E2) and beta-dienestrol enhance anchorage-independent proliferation (AIP) of SV40-immortalized human endometrial stromal cells in the rank order of DES > E2 > beta-dienestrol. The anti-estrogenic compound tamoxifen inhibits DES-induced AIP. The magnitude of DES-induced AIP increases with prolonged duration of treatment. After 11 months of chronic treatment with 0.1 nM DES, AIP was 20-fold higher than in vehicle-treated control cultures. Expression of the estrogen receptor was altered by treatments with DES in parallel with increased capacity for AIP. These conditionally immortal human endometrial stromal cells appear to be a good model for estrogen-induced transformation of human cells.
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PMID:Estrogen-induced anchorage-independence in human endometrial stromal cells. 755 29

Conflicting results have been obtained with regard to the estradiol receptor (ER) capacity of human prostatic tissue. Human prostatic DU-145 cells have been found to be ER-negative with immunohistochemical assays. The object of this investigation was to determine if whole DU-145 cells, which had been grown in monolayer culture, have ER and, if so, to confirm the finding with antiestrogens. After cells had been lysed, a Bmax of 44.7 +/- 4.0 fmol/mg (Kd = 0.6 +/- 0.6 nM) was obtained. Subcellular localization studies showed that the estrogen receptor level in the cytoplasmic fraction was approximately 10 times higher than in the nuclear fraction. Competitive binding studies showed that tamoxifen, DES, and acetylsalicylic acid decreased estradiol binding. The dissociation constants and relative affinities for tamoxifen, DES, and acetylsalicylic acid were 0.2 nM (281.7%), 0.2 nM (224.0%), and 0.8 nM (78.43%), respectively. However, 5 alpha-dihydrotestosterone and metabolites of acetylsalicylic acid had no effect in competitive binding studies. These results may contribute to a better understanding of prostatic carcinogenesis, which may in turn lead to more effective treatment.
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PMID:Binding of estradiol to whole prostatic DU-145 cells in the presence and absence of tamoxifen and acetylsalicylic acid. 756 95

Retinoid response pathways involve retinoic acid receptors (RARs) and retinoid X receptors. N-(4-hydroxyphenyl) retinamide (4-HPR), a derivative of all-trans-retinoic acid (RA) is currently in clinical trials as a chemopreventive agent for breast cancer. The issue whether 4-HPR mediates its biological actions via classical retinoid receptor pathways remains to be investigated. In this study, we provide several lines of evidence that 4-HPR mediates its biological actions via a novel pathway(s) that does not involve the classical retinoid receptor pathways. For example, 4-HPR was more potent than RA as an antiproliferative agent and inhibited growth of otherwise RA-resistant human breast carcinoma cells. Exposure to 4-HPR resulted in the generation of DNA fragmentation with subsequent cell death in both RA-positive estrogen receptor (ER)-positive as well as RA-refractory ER-negative breast carcinoma cell lines. N-(4-Methoxyphenyl)retinamide (4-MPR), which is the major 4-HPR metabolite in circulation, was biologically inert in this system. 4-HPR and 4-MPR bound poorly to the RAR alpha, beta and gamma in vitro and only minimally activated the retinoic acid receptor element (RARE) and retinoid X receptor response elements (RXREs) in human breast carcinoma cells. Neither 4-HPR nor 4-MPR are metabolized to any of the known conventional retinoids. In addition, 4-HPR or 4-MPR transactivation of RAREs or RXREs transfected into MCF-7 and MDA-MB-231 cells was not noted at 48 h. Nevertheless 4-HPR-mediated cell death was observed at 48 h, further suggesting that neither 4-HPR nor 4-MPR are metabolized to retinoids which activate the RAREs or RXREs in breast carcinoma cells. Furthermore, unlike RA, which exhibited anti-AP1 activity, 4-HPR inhibition of growth did not involve anti-AP1 activity. These results suggest that 4-HPR acts by a unique pathway that is not mediated by retinoid receptors.
Carcinogenesis 1995 Oct
PMID:N-(4-hydroxyphenyl)retinamide (4-HPR)-mediated biological actions involve retinoid receptor-independent pathways in human breast carcinoma. 758 55

Administration of a single i.v. injection of 50 mg N-methyl-N-nitrosourea (MNU)/kg body wt to 50- to 60-day old virgin rats, 120-day-old virgin rats, and 120-day-old parous rats (Sprague-Dawley; n = 18-37) resulted in a high incidence of mammary carcinomas in the virgin animals (97.3% in 50- to 60-day-old virgin rats; 75.0% in 120-day-old virgin rats), but mammary carcinomas did not develop in the parous rats. The concentrations in serum of various mammotropic hormones were measured in identical groups of rats at the time of MNU treatment. Growth hormone (GH) concentration was significantly reduced in parous rats, as compared with young or age-matched virgin rats. The concentrations of prolactin, 17 beta-estradiol, progesterone, corticosterone and thyroxine were not significantly altered in the parous rats compared to the two groups of virgin animals. Histological examination of the mammary glands from the three groups of rats showed that the epithelia of the parous animals were in a stage of regression, whereas the mammae of the young virgin rats showed the highest degree of lobulo-alveolar development. The levels of estrogen receptor (ER), epidermal growth factor (EGF) receptor (EGF-R) and GH receptor (GHR) in the mammary glands of the animals were also measured. We found a reduction in the receptor levels for both estrogen and EGF in mammary tissues from parous animals. Receptors for GH were present in normal mammary tissues from both virgin and parous rats. We hypothesize that the reduction in the circulating concentration of GH caused the reduced susceptibility of parous rats to mammary carcinogenesis possibly by decreasing the levels of ER and/or EGF-R in the mammary gland.
Carcinogenesis 1995 Nov
PMID:Refractoriness to mammary tumorigenesis in parous rats: is it caused by persistent changes in the hormonal environment or permanent biochemical alterations in the mammary epithelia? 758 8

Dietary phytoestrogens have been implicated in infertility among ruminants and may relate to human breast cancer risk. Formononetin is an isoflavonoid phytoestrogen found in animal fodder and in certain human foodstuffs. To investigate a possible mechanism by which phytoestrogens might influence mammary carcinogenesis, this study examined the capacity of formononetin to stimulate mammary gland proliferation. Formononetin was administered to castrated female BALB/c mice by daily subcutaneous injection; then mammary gland proliferation and estrogen receptor expression were quantified, and plasma prolactin levels were measured. A preliminary dose-finding study demonstrated an estrogenic effect on vaginal cytology when formononetin was injected at 40 mg/kg sc. Peak plasma concentrations of 2.5 +/- 0.8 (SD) micrograms/ml at two hours and peak mammary tissue concentrations of 2.0 +/- 0.2 ng/mg tissue at four hours were noted after a single injection at this minimally bioactive dose. Among animals treated with formononetin at 40 mg/kg/day for five days, mammary gland proliferation was enhanced 3.3-fold over saline-treated controls and was comparable to that of animals treated with estradiol-17 beta at 1 microgram/kg/day for five days. Mammary tissue estrogen receptor expression was 2-fold higher among the formononetin-treated animals (P < 0.01 vs. saline-treated controls), and plasma prolactin concentrations were increased 1.7-fold (P < 0.001 vs. saline-treated controls). In subsequent in vitro binding studies, formononetin competitively bound murine mammary estrogen receptors, but with a relative binding affinity 15,000 times less potent than that of estradiol-17 beta. The results demonstrate an ability of formononetin to support mammary gland proliferation. However, the estrogenic potency of formononetin appears extremely weak compared with that of estradiol-17 beta and is roughly proportional to estrogen receptor-binding capacity.
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PMID:Proliferative response of mammary glandular tissue to formononetin. 764 82

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

We recently described the establishment and the characterization of two rat endometrial adenocarcinoma cell lines which we called RUCA-I and RUCA-II. Despite fairly high estrogen receptor levels neither cell line responded to estradiol in conventional cell culture conditions on plastic and in the presence of serum. A limited hormonal response to the antiestrogen tamoxifen was detectable in RUCA-I but not in RUCA-II cells. To advance our cell culture conditions we plated RUCA-I cells on a layer of reconstituted basement membrane (Harbor Matrix) in the presence of a serum-free defined medium. These cell culture conditions induced hormone responsiveness of RUCA-I cells and permitted a stimulation of proliferation by estradiol. Further, two estradiol-induced secretory proteins with an apparent molecular weight of 115 kD and 60 kD could be identified by SDS-gelelectrophoresis if analyzed under reducing conditions. These proteins migrated as a single band in a non-reducing electrophoresis gel and were identified as components of the complement C3 system. Additionally, our results suggest that the effects of extracellular matrix and hormones on the expression of these proteins are additive. We conclude that processes of functional differentiation are most likely to occur in this in vitro model, particularly since the expression of components of the complement C3 system was under estrogenic control. Complement C3 proteins represent major estradiol-inducible secretory protein of the immature rat uterus in vivo. Culturing RUCA-I cells on top of a layer of reconstituted basement membrane provides a novel tool to study the importance of the extracellular environment on the hormone-induced gene expression in endometrial carcinogenesis in vitro.
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PMID:Extracellular matrix induces hormone responsiveness and differentiation in RUCA-I rat endometrial adenocarcinoma cells. 769 47

Effects of estrogens on the cytoplasmic microtubule network were examined by the indirect immunofluorescence method using anti-beta-tubulin antibody. Estradiol, a naturally occurring estrogen, decreased the amount of cytoplasmic microtubule fibers during interphase in the human breast cancer cell lines MCF-7 and MDA-MB-231. Since MDA-MB-231 is an estrogen receptor-negative cell line, estradiol-induced microtubule disruption seems to be independent of estradiol binding to receptors. The effective concentration of estradiol required for induction of microtubule disruption in 50% of the cells (EC50) was 81 microM for MCF-7 cells and 82 microM for MDA-MB-231 cells. A synthetic estrogen, diethylstilbestrol, also induced a decrease in microtubule fibers, with an EC50 value of 48 microM for MCF-7 cells and 50 microM for MDA-MB-231 cells. When estrogen-treated and microtubule-depolymerized cells were washed and the medium was replaced with fresh, intracellular microtubule networks reappeared within 3 h. When MCF-7 cells were cultured for 4 days with estradiol (50 microM), cell growth was completely inhibited. However, estrone affected the microtubule network and cell proliferation only slightly. These results suggest that estradiol-induced microtubule disruption is closely related to its inhibitory effect on cell growth.
Carcinogenesis 1994 Sep
PMID:Microtubule disruption induced by estradiol in estrogen receptor-positive and -negative human breast cancer cell lines. 792 80

To investigate whether sex hormone receptors exist in the resected non-small-cell lung cancer in human beings and to determine a link between the pulmonary carcinogenesis and the sex receptor status of the lung cancer tissue, we reviewed the case histories of 64 patients who underwent resectional therapy for non-small-cell lung cancer between 1988 and 1990 (38 men and 26 women, mean age 65 years). Mouse monoclonal immunoglobulin G antibodies were used for immunohistochemical detection of estrogen receptors and progesterone receptors in the acetone-fixed specimen. The control group consisted of normal lung tissue from the patients with and without bronchogenic carcinoma and breast cancer tissue from the patients with estrogen and progesterone receptor immunoreactivity. No evidence of estrogen and progesterone receptor immunoreactivity was present in the normal lung tissue. All but two patients had immunoreactivity (97%) for estrogen receptors in the lung cancer tissue (p < 0.001). The differences for sex and for histologic subtypes were not statistically significant. Observed actuarial survival at 3 years was 83% for all patients with estrogen receptor immunoreactivity: 94% for women and 75% for men (p < 0.05). We found no correlation between the hormone receptor status and the type, clinical features, or prognosis of the non-small-cell lung cancer. We conclude that an abundance of estrogen receptors is hosted only in cancerous tissue, not in normal pulmonary tissue. Improved identification and definition of estrogen receptors in the nontarget lung cancer tissue offer a possibility of antiestrogen therapy for patients with advanced bronchogenic carcinoma.
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PMID:Sex hormone receptors in non-small-cell lung cancer in human beings. 802 59


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