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

The proliferative activity of 163 primary breast cancers was assessed by immunocytochemistry with the mouse monoclonal antibody Ki-67, which recognizes a nuclear antigen expressed in all phases of the cell cycle except for Go. The overall frequency distribution of Ki-67 staining was of exponential type, with percentage of positive staining cells ranging from 0.3 to 88.3%, with a median value of 10.1%. No relationship was observed between Ki-67 values and menopausal status of patients. A significant positive correlation was found between Ki-67 values and tumor grade, especially mitotic grade. Estrogen Receptors (ER) were assayed by immunocytochemistry with ER-ICA method and by dextran-coated charcoal method (DCC) in 129 and 141 tumors, respectively. A negative correlation was found between the ER content by both methods and Ki-67 score. Eighty-nine percent of cases with Ki-67 value less than 10.1% contained more than 10% ER-ICA-positive cells. Progesterone receptors (PgR) were assayed by immunocytochemistry with PgR-ICA method and by DCC in 62 and 141 tumors, respectively. A negative correlation was observed between the PgR content by both methods and Ki-67 score. No correlation was found between Ki-67 score and lymph node involvement by tumor. These findings suggests that Ki-67 score could be used as an independent prognostic marker, useful to distinguish different risk for recurrence within the two clinically heterogeneous groups of N- and N+ patients.
 ...
PMID:Assessment of proliferative rate of breast cancer by Ki-67 monoclonal antibody. 230 19

In a blinded, prospective, dose-response pilot study of continuous estrogen-progestin replacement therapy, 77 thin, nonsmoking, white women, who were 12 to 60 months postmenopausal and had normal medical histories, were randomly assigned to receive one of five dose combinations of daily ethinyl estradiol and norethindrone acetate (20 micrograms and 1.0 mg, 10 micrograms and 1.0 mg, 10 micrograms and 0.5 mg, 5 micrograms and 1.0 mg, and 5 micrograms and 0.5 mg) or conjugated estrogens 0.625 mg on days 1 to 25 and medroxyprogesterone acetate 10 mg on days 16 to 25. An additional 10 women meeting the same criteria served as a comparison group by taking calcium only. During 12 months of therapy, continuous users had significantly less vaginal bleeding and spotting than did sequential users. As compared with baseline values, bone metabolism and computerized tomographic measurements of vertebral trabecular bone density at month 12 indicated reduced bone turnover and increased density in hormone users. Endometrial biopsy specimens were negative for hyperplasia and neoplasia. The continuous ethinyl estradiol-norethindrone acetate tablet, even at the lowest doses studied, provided the same salutary effects on bone, endometrium, and postmenopausal symptoms as sequential therapy while minimizing annoying vaginal bleeding and spotting.
 ...
PMID:A study of combined continuous ethinyl estradiol and norethindrone acetate for postmenopausal hormone replacement. 230 27

Previously, we reported that relatively high micromolar concentrations of the liver tumor promoter 17 alpha-ethinyl estradiol (EE2) stimulated DNA synthesis and enhanced the DNA synthetic response to epidermal growth factor (EGF) in primary cultures of female rat hepatocytes [J.D. Yager, B.D Roebuck, T.L. Paluszcyk, and V.A. Memoli, Carcinogenesis 7, 2007-2014 (1986); Y.E. Shi and J.D. Yager, Cancer Res. 49, 3574-3580 (1989)]. In this study, our goal was to examine the metabolism of EE2 in cultured hepatocytes. After 4, 24, and 48 hr of culture, hepatocytes maintained their ability to convert up to 95% of a 4 nM concentration of [3H]EE2 to polar conjugates within 4 hr. EE2 at 2 microM was also 95% metabolized within 4 hr. HPLC analysis of the metabolites confirmed the rapid disappearance of [3H]EE2 and the formation of polar conjugates as detected by organic extraction. HPLC separation of hydrolyzed conjugates indicated that the major aglycone was the parent compound, EE2. In general, the metabolites differed both qualitatively and quantitatively from those reported in vivo in the rat. The rapid metabolism of EE2 by hepatocytes in culture may, at least in part, explain the high concentrations of EE2 required to stimulate DNA synthesis in cultured hepatocytes and to potentiate the response to EGF.
 ...
PMID:Metabolism of the liver tumor promoter ethinyl estradiol by primary cultures of rat hepatocytes. 231 17

An immunohistochemical procedure was applied which allows accurate localization of DNA lesions within organs and tissues of rats given 3,2'-dimethyl-4-aminobiphenyl (DMAB) using polyclonal antibodies against DMAB-DNA adducts. Dose-related nuclear staining was observed in organs regardless of DMAB-carcinogenic organotropism. In the male accessory sex organs, the lateral lobe of the prostate, a non-target site, demonstrated a similar staining intensity to that found for the ventral prostate and seminal vesicle, target sites. Orchiectomy and pretreatment with ethinyl estradiol resulted in a moderate to slight decrease in binding in the accessory sex organs. No observable decrease in staining intensity was evident in most organs 168 h after the administration of DMAB. These findings suggest that DNA adduct formation itself is not necessarily sufficient for tumor induction.
 ...
PMID:Immunohistochemical demonstration of carcinogen-DNA adducts in target and non-target tissues of rats given a prostate carcinogen, 3,2'-dimethyl-4-aminobiphenyl. 232 4

UM-EC-2 was established from a patient with poorly differentiated stage IB endometrial carcinoma. This cell line produces tumors in nude mice that have the same histological features as the patient's tumor. UM-EC-2 cells express b2-microglobulin, the epidermal growth factor receptor (EGF), and the H blood group antigen. This membrane antigen phenotype is consistent with cells of human endometrial origin. The karyotype of UM-EC-2 is fairly complex, with rearrangements affecting all chromosomes except 3, 10, 14, 19, and 20. There were two populations of cells, a hyperdiploid population with a modal number of 53-55 and a hypertetraploid population with a modal number of 109. A postulated sequence of events before and after tetraploidization is suggested based on the number of copies of individual chromosomes and rearrangements. Comparison of the UM-EC-2 karyotype to that of UM-EC-1 (a previously described line from a different patient with endometrial carcinoma) revealed that the two lines share eight very similar chromosome changes, which include loss of most of chromosome 4, breakpoints affecting proximal bands on 8p, loss of most of 9q, a breakpoint at 12q22, loss of 13q, breakpoints in proximal bands on 18q, and a breakpoint at 22p11. These changes may represent nonrandom chromosome abnormalities in poorly differentiated endometrial cancer. Estrogen (ER) and progesterone (PgR) receptors were not detected in either the primary tumor or the cell line. Nevertheless, UM-EC-2 cells were very sensitive to growth inhibition by tamoxifen (TAM) in vitro. One micromolar TAM caused 50% inhibition of cell growth, 2.5 microM caused cytostasis, and 5 microM TAM was cytotoxic, killing all cells after 5-7 days of exposure to the drug. Paradoxically, 100 nM estradiol (E2) caused a moderate increase in the growth of the cells but it did not prevent or reverse growth inhibitory effects of TAM. These findings support the concept that in some tumors TAM causes growth inhibition by an ER-independent mechanism. UM-EC-2 cells were also sensitive to growth regulation by EGF. Thus, these cells provide a new in vitro model of human endometrial cancer in which the roles of both TAM and EGF as growth regulatory substances can be investigated.
 ...
PMID:Establishment and characterization of UM-EC-2, a tamoxifen-sensitive, estrogen receptor-negative human endometrial carcinoma cell line. 234 64

Epidermal growth factor (EGF) has been shown to be important in regulating the growth of breast cancer cells in vivo because of its mitogenic action on some breast cancer cell lines in vitro. Immunocytochemical analysis of EGF receptor (EGFr) was carried out on frozen sections in 134 primary breast cancer patients. Overall 68 of 134 (51%) of the tumors were EGFr positive. There was no correlation between EGFr positivity and menopausal status. Regarding the histopathological features, no significant correlations were observed between EGFr expression and tumor size, grading and lymph nodes status. Estrogen (ER) and progesterone (PgR) receptors were detected by an immunocytochemical assay and an equal distribution of EGFr was found regarding steroid hormonal receptors expression. Finally, there was only a positive trend between the proliferative activity of the tumors, as measured by Ki-67 antibody, and the amount of EGFr. Our results suggest the presence of a subclass of breast tumors, characterized by the absence of ER and/or PgR and the presence of EGFr, whose growth appears to be mediated by autocrine growth factors rather than by steroid hormones. The overall picture is that of an independent relationship between EGFr expression and the known prognostic factors in breast cancer.
 ...
PMID:Immunocytochemical determination of epidermal growth factor receptor with monoclonal EGFR1 antibody in primary breast cancer patients. 236 59

Estrogen (ER), progestin (PGR), and androgen (AR) receptors were assayed in cytosols prepared from 38 various intracranial tumors. The receptors were in the following proportions (number of receptor-positive/number of tumors examined): meningiomas were positive for PGR (4/6) and AR (2/5); glioblastomas were also positive for PGR (3/21) and AR (7/21); astrocytomas were positive only for PGR (4/5); and oligodendrogliomas only for AR. In two hamartomas AR was present, while in one chordoma both PGR and AR were present. In this latter tumor ER were not assayed due to insufficient material. The receptors were present in concentrations between 10 and 20 fmol/mg protein. Exceptions were two meningiomas and a chordoma with a high concentration of PGR and AR. Our results support the notion that a proportion of intracranial tumors contains sex steroid receptors, and some of these tumors might be hormonally dependent.
 ...
PMID:Sex steroid receptors in intracranial tumors. 237 66

Estrogen (ER), progesterone (PR), and androgen receptors (AR) were determined by saturation analysis in 100 cases of primary ovarian cancer and correlated with patient survival. The mean follow-up period was 5.4 years (range, 4 to 6.5 years). Positivity for PR was associated with a significantly better survival rate (P less than 0.05). A similar observation was made for AR (P less than 0.05). Tumor ER content did not correlate with survival. Ten patients with tumors that had negative results for both PR and AR all died of the disease. In 91 cases of serous, endometrioid, and mucinous carcinomas, grade, stage, and tumor PR content, but not AR content, were identified as independent prognostic factors with the use of the Cox proportional hazards model. The relative risk of patients with PR-negative tumors was 2.3 times higher than that of patients with tumors containing high (greater than or equal to 30 fmol/mg) PR levels.
 ...
PMID:Survival of patients with ovarian cancer. Apart from stage and grade, tumor progesterone receptor content is a prognostic indicator. 238 2

Twenty consecutive weekly sc injections of 50 mg/kg body weight of 3,2'-dimethyl-4-aminobiphenyl (DMAB), a multipotential carcinogen, were given to male F344 rats and subsequently groups of animals were treated with dietary ethinyl estradiol (EE, 2.5 ppm) or methyltestosterone (MT, 300 ppm) for up to 40 weeks. Prostate carcinomas were found in 4 out of 32 rats given DMAB followed by MT and in 2 out of 29 rats given DMAB alone. Atypical hyperplasia of the prostate epithelium in these two groups was found in 22% and 14%, respectively. Neither carcinoma nor atypical hyperplasia was seen in the prostate of animals given DMAB followed by EE. In other organs, tumors were frequently found in the ear duct, skin, and large intestine and less frequently in the lung, preputial glands, small intestine and liver. EE significantly suppressed tumor incidence of the ear duct and sebaceous glands while increasing the incidence of liver tumor and mesothelioma. The present data indicates DMAB to be a useful carcinogen for the induction of prostate carcinomas in rats.
 ...
PMID:Rat prostate as one of the target organs for 3,2'-dimethyl-4-aminobiphenyl-induced carcinogenesis: effects of dietary ethinyl estradiol and methyltestosterone. 241 60

The presence of the tumor marker CA 125 was studied in the cervices of healthy women. Immunohistochemical staining of normal cervical tissue demonstrated the presence of CA 125 in the tall columnar cells of the endocervical epithelium but not in the ectocervical squamous epithelium. We measured very high levels of CA 125 in liquefied cervical mucus from women with regular menstrual cycles. At midcycle, levels ranged from 14,200 to 153,000 U/ml (n = 13) in cervical mucus, while normal levels less than 35 U/ml were found in the corresponding serum samples. Levels of CA 125 in cervical mucus are comparable to the high levels found in cyst fluids from ovarian tumors (median 24,600 U/ml, n = 25). When secretion of cervical mucus was stimulated by ethinyl estradiol, equally high levels were found (7900 to 138,000 U/ml, n = 10). We conclude that the tumor marker CA 125 is synthesized and secreted by normal endocervical cells. Apparently an effective barrier exists between the endocervical mucosa and the circulation.
 ...
PMID:The tumor marker CA 125 is a common constituent of normal cervical mucus. 242 37


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>