Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-like growth factor-I (IGF-I) is considered an important local mitogenic growth factor involved in autocrine/paracrine regulation of human breast cancer cell proliferation. We have characterized the IGF-I-like activity and studied its hormonal regulation by estradiol in the MCF-7 human breast cancer cell line. We found that the radioimmunoassayable IGF-I-like activity measured in conditioned medium (CM) is predominantly due to the presence of IGF-binding proteins (IGFBP). Acid chromatography demonstrated that most of the IGF-I-like activity eluted in the high molecular weight fractions and less than 10% co-eluted with authentic IGF-I (mol wt 7500). Binding protein activity measured by a 125I-IGF-I-ligand binding IGFBP-assay was present in these same high molecular weight fractions. SDS-polyacrylamide gel electrophoresis and 125I-IGF-I-ligand blot analysis of the CM showed the presence of two species of binding proteins of 29 kDa and 41 kDa molecular weight which demonstrated specific 125I-IGF-I binding activity. Estradiol did not stimulate IGFBP activity as assessed by the IGFBP-assay and as indirectly reflected by the IGF-I-like activity in the high molecular weight fractions. We conclude that the IGF-I-like activity in CM from human breast cancer cell cultures is predominantly due to the presence of IGFBP. Binding proteins of apparent molecular weight 29 kDa and 41 kDa are present in CM from MCF-7 cells. Assessment of their hormonal regulation showed that estradiol did not stimulate IGFBP. However, this needs to be assessed more stringently using better quantitative estimations for BP. The IGF-binding proteins may have an important role in the regulation of tumor cell growth by influencing the local concentrations and receptor mediated actions of IGF-I.
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PMID:Characterization and hormonal regulation of radioimmunoassayable IGF-I (insulin-like growth factor I) like activity and IGF-binding proteins secreted by human breast cancer cells. 170 Jun 62

[3H]Estradiol can bind to a specific protein in normal rat pancreatic acinar cells. Electron microscopic immunocytochemical analysis has shown this protein to be localized primarily in the rough endoplasmic reticulum and mitochondria. Rat exocrine pancreatic tumor cell lines, whether grown in tissue culture (AR42J) or as a tumor mass after sc injection into rats (DSL-2), lacked detectable amounts of this [3H]estradiol-binding protein (EBP), as determined by the dextran-coated charcoal assay. Furthermore, primary exocrine pancreatic neoplasms induced with the carcinogen azaserine contained little or no detectable [3H]estradiol-binding activity. However, electron immunocytochemical studies of transformed cells indicated the presence of material that cross-reacted with antibodies prepared against the [3H]EBP. The immunopositive reaction in transformed cells was localized almost exclusively in lipid granules. Such lipid organelles in normal acinar cells, although present less frequently than in transformed cells, have never been observed to contain EBP-like immunopositive material. Presumably, the aberrant localization of EBP in these acinar tumor cells results in loss of function of this protein, which in normal pancreatic acinar cells appears to exert a modulating influence on zymogen granule formation and the process of secretion.
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PMID:Marked differences in immunocytological localization of [3H]estradiol-binding protein in rat pancreatic acinar tumor cells compared to normal acinar cells. 190 Feb 33

We have studied the estradiol sensitivity of primary human breast carcinomas in organ culture in a prospective pilot series of 109 tumors. The effect on plasminogen activator (PA) production was used as the end-point of estrogen action. We found that: (i) All tumors secreted detectable levels of urokinase-type PA (uPA); the level of basal uPA production was markedly heterogeneous but showed a weak association with the level of estrogen receptor positivity (p = 0.049). (ii) Only 23.5% of the tumors secreted tissue-type PA (tPA) in addition to uPA; a higher proportion of these tumors had histological characteristics indicative of good prognosis (18% vs. 3% of tumors secreting only uPA). (iii) Estradiol modulated uPA production and this effect was receptor-mediated. (iv) Responsiveness to estradiol was limited to a subset (25 of 60 or 41.7%) of estrogen and progesterone-receptor-positive tumors. (v) Of 20 evaluable patients with lymph-node and receptor-positive breast cancer who received adjuvant anti-estrogen therapy, 11 were identified as estradiol-sensitive by the in vitro PA assay; of these, 10 had no evidence of disease after a median follow-up period of 3+ years. In contrast, of 9 patients with tumors identified as estradiol-insensitive, 4 developed metastases within 3+ years of follow-up. (vi) Consistent with the previously reported inhibitory effect of corticosteroids on uPA production in organ cultures of human tumors, the basal culture level of uPA produced by tumors from patients receiving corticosteroids at the time of surgery was significantly lower than the level of uPA in the remaining tumors (p = 0.029). Also, tumors from patients receiving thyroid hormone, known to stimulate uPA in vitro, showed a slight trend toward increased production of uPA. These results show that hormone effects on tumor PA production are qualitatively similar in organ culture and in the host. This and the emerging individual correlation between sensitivity to estradiol in vitro, as determined by PA, and the clinical effectiveness of anti-estrogen therapy, underscore the potential usefulness of the organ culture approach.
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PMID:Estradiol modulation of plasminogen activator production in organ cultures of human breast carcinomas: correlation with clinical outcome of anti-estrogen therapy. 190 Dec 98

Experiments were performed to determine the effect of neonatal estrogen treatment on the expression of the proto-oncogene c-fos in the BALB/c mouse cervicovaginal tract. Estradiol induces the expression of c-fos in the normal mouse cervicovaginal tract. However, c-fos expression was not stimulated by estradiol in the cervicovaginal tracts of mice that received neonatal estrogen treatment. In addition, the level of expression of c-fos by the estrogen- and progesterone-induced murine cervicovaginal LJ6195 tumor was similar to that in the normal vaginal tract following estradiol stimulation and was not regulated by estradiol.
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PMID:Alteration of proto-oncogene c-fos expression in neonatal estrogenized BALB/c female mice & murine cervicovaginal tumor LJ6195. 191 5

The nutritional and immunological status have been evaluated in 28 consecutive patients with esophageal cancer. Patients (21 male and 7 female), had a mean age of 61 years, ranging from 34 to 84 years. The tumor histological type was squamous in 25 patients. A melanoma, an oat cell carcinoma and a adenocarcinoma were observed in the remaining cases. The nutritional status was assessed by means of weight loss, triceps skinfold, midarm muscle circumference and serum levels of albumin and transferrin. On the basis of this data the patients were divided into two groups: A, 19 patients (68%), normal nourished group (or with a mild malnutrition) and B, 9 patients (32%) with a severe malnutrition. The immunological status was assessed by determining the lymphocyte absolute number (H-6000-Technicon), the T-Lymphocyte sub-populations (flow-cytometry with monoclonal antibodies--Ortho Diagnostic System) and the patient's response to intradermally placed recall antigens (Multitest Merieux). Significative immunological abnormalities were found only in malnourished patients, group B (p less than 0.05). Moreover a reduction of OKT4 helper (less than 30%) and the inversion of OKT4/OKT8 ratio (less than 0.9%) were also observed only in the malnourished group (p less than 0.01). Therefore, we conclude that acquired immunodeficiency, when present in patients with esophageal cancer, is due to the severe malnutrition rather than to the cancer itself.
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PMID:[Relationship between nutritional and immunologic status in patients with esophageal cancer]. 194

One of the critical issues in risk assessment for chemical carcinogens is the evaluation of dose-response relationships for tumor promoters. In the studies reported here we have systematically investigated dose-response relationships for the liver tumor-promoting actions of 17 alpha-Ethinylestradiol (EE2) following a single injection of diethylnitrosamine (200 mg/kg) to ovariectomized female rats. Parameters measured included tumor incidence, gamma-glutamyltranspeptidase (GGT) positive foci, serum prolactin and serum EE2. The length of tumor promotion ranged from 30 to 60 wk. Results showed a linear increase in GGT-positive foci between doses of 16 and 90 micrograms EE2 kg/d for 30 wk. This was associated with corresponding increases in liver tumor incidence at 60 wk. Seventy-five percent of the animals had either hepatocellular adenoma or hepatocellular carcinoma in the group promoted with 90 micrograms EE2/kg for 60 wk. No liver tumors were evident in either controls or animals receiving estrogen only. Serum prolactin concentrations were elevated in all estrogen-treated groups. In summary, our studies have evaluated dose-response relationships for GGT-positive foci and tumor incidence in a two-stage model for hepatocarcinogenesis using EE2 as the promoting agent.
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PMID:Dose-response relationships in promotion of rat hepatocarcinogenesis by 17 alpha-ethinylestradiol. 196 81

We have previously reported (Berebbi et al., 1988) that in athymic nude mice, Polyoma virus induces mammary adenocarcinomas (MAC) at high frequency and exclusively in females. In the present study we show that in nude mice: (1) Ovariectomy results in a reduced frequency of MAC and a longer latency period of induction. When testosterone is administered to ovariectomized females, tumor induction is drastically reduced. (2) When estradiol is administered continuously to ovariectomized females the incidence and kinetics of MAC induction are the same as in control females. (3) MAC are induced in castrated males administered with estradiol although only osteosarcomas are observed in control males. (4) The tumor cells are found to harbor functional estradiol and progesterone receptors. (5) MAC can be transplanted from females to males, indicating that tumor growth is estradiol independent. (6) Estradiol is required only between day 10 and day 20 following polyoma injection, whereas the first tumors are detected only around day 60. Our results indicate that MAC induction by Polyoma virus in nude mice is estradiol-dependent during a short initiation period and that tumor progression is estradiol-independent in spite of the fact tumor cells carry functional estradiol and progesterone receptors.
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PMID:Estradiol dependence of the specific mammary tissue targeting of polyoma virus oncogenicity in nude mice. 197 Jan 53

Natural killer (NK) cells are putative components of the cellular immune response to transformed cells. Since both estradiol treatment and ras-oncogene overexpression enhance tumorigenicity of hormone-dependent breast-cancer cells, we studied the effects of estrogen and of the activated v-Ha-ras oncogene on NK susceptibility of MCF-7 human breast-cancer cells. MCF-7 cells were sensitive to cytolysis mediated by resting and IL2-activated peripheral-blood non-adherent lymphocytes. Lysis appeared to be mediated by NK cells, since it was abrogated by treatment of effector cells with alpha-CD16 monoclonal antibody (MAb) plus complement (c'). Estradiol treatment of MCF-7 cells was able to significantly increase their sensitivity to the lysis by IL2-activated and unactivated peripheral-blood lymphocytes, as early as 24 hr throughout 10 days of hormone treatment. Hormone-insensitive, estrogen-receptor-negative breast-cancer cells (BT20) did not change their NK susceptibility after estradiol treatment. Increased NK susceptibility was also observed in v-Ha-ras-transfected and oncogene product overexpressing MCF-7 cells (MCF-7-ras) with respect to cells transfected with the selectable gene marker gpt alone (MCF-7-gpt). Overexpression of v-Ha-ras appeared to be able to bypass the need for estrogen to increase NK susceptibility, since estradiol-treated MCF-7-ras cells were not lysed more than untreated MCF-7-ras cells. The enhancement of NK susceptibility observed after both estradiol treatment and v-Ha-ras overexpression suggests that the hormone-mediated and the ras-oncogene-mediated signalling systems share events involved in the control of tumor-cell/host-effector-cell interactions.
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PMID:Enhancement of natural-killer-cell susceptibility of human breast-cancer cells by estradiol and v-Ha-ras oncogene. 199 53

Estradiol-linked nitrosoureas are offering new perspectives in the antineoplastic chemotherapy of estradiol-receptor positive mammary carcinomas. In such a molecule estradiol has the function of a carrier which brings about a specific accumulation of the anticancer drug in estradiol-receptor containing tumor cells. However, there is only little knowledge about the pharmacokinetic behavior of this new group of anticancer agents. For that reason a new comprehensive technique of catheterisation, blood sampling, sample preparation and sample analysis with high-pressure liquid chromatography (HPLC) for preclinical pharmacokinetic studies with estradiol-linked nitrosoureas and their metabolites has been developed. N-(2-Chloroethyl)-N-nitroso-carbamoyl-L-alanine-estradiol-17-ester (CNC-alanine-estradiol-17-ester) and N-(2-chloroethyl)-N-nitroso-carbamoyl-L-alanine (CNC-alanine) were used as test compounds. The drugs were tested in female Sprague-Dawley rats with chemically induced mammary carcinomas. The laboratory animals were supplied with two catheters prior to the pharmacokinetic experiments. The blood samples were drawn from the vena cava catheter after the drug had been applied through a vena jugularis catheter. The compounds were extracted from plasma with C18 silicagel reversed phase cartridges. The clean-up technique delivered clear samples only slightly contaminated with the biological matrix. The recovery from plasma was 75 +/- 5% for the hormone-linked CNC-alanine-estradiol-17-ester and 70 +/- 5% for the unlinked CNC-alanine. The analysis was carried out by means of HPLC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A new comprehensive technique of catheterisation, blood sampling, sample preparation and sample analysis by means of high-pressure liquid chromatography for pharmacokinetic studies with estradiol-linked nitrosoureas and their metabolites. 208 Sep 36

The effects of estradiol (E), medroxyprogesterone acetate (MPA), and tamoxifen (TAM) on the growth of a human ovarian carcinoma cell line, BG-1, were evaluated using a tumor clonogenic assay (HTCA). BG-1 contains significant quantities of estrogen and progesterone receptors. Growth inhibition by TAM and growth stimulation by MPA were demonstrated using continuous drug exposure. Estradiol resulted in a marginal increase in colony formation. With each of these three drugs, the greatest response occurred in the larger colonies (generally greater than or equal to 60 microns). Combinations of each of these three steroidal agents with three different cytotoxic drugs were studied in the HTCA. Synergistic activities were produced with TAM combined with either cisplatin or doxorubicin. Additive effects were seen with TAM and cyclophosphamide. Although predominantly additive or synergistic, the effects were variable with MPA and all three cytotoxic agents. Combinations of estradiol with cytotoxic agents were no more active than the cytotoxics alone. These findings indicate a biological rationale for hormonal manipulation as therapy in ovarian cancer.
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PMID:The effects of estrogen, progesterone, and tamoxifen alone and in combination with cytotoxic agents against human ovarian carcinoma in vitro. 213 65


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