Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The question of whether estrogen receptor assay predicts for chemotherapy response and, if so, how, is currently controversial. Two papers have recently appeared with widely differing results. Both papers use retrospective analysis and are so heterogeneous as regards assay criteria for positivity, prognostic variable and drugs used that they cannot in truth be meaningfully compared. Resolution of the question will probably have to await prospectively designed trials.
Cancer Clin Trials 1979
PMID:The dilemma of estrogen receptors and the response rate to cytotoxic chemotherapy. A problem of comparability analysis. 51 31

Seventy-eight advanced breast cancer patients, most of whom had had prior treatment, were treated with the synthetic antiestogen tamoxifen. The overall objective response rate was 27% (21/78). An additional 19% (15/78) showed disease stabilization. Sixty-seven percent (14/21) of the responses were in soft tissue sites, 24% (5/21) on bony sites and one each occurred in liver and nodular lung disease. Forty percent of patients with soft-tissue disease alone responded, while less than 10% of patients with visceral disease showed responses in visceral sites. The response rate was 28% among patients with a known positive estrogen receptor (ER) assay. It was 21% among patients who had previously received cytotoxic drugs. Toxicity was mild and was seen in nausea and vomiting, hot flushes and vaginal bleeding, and occasional myelosuppression. One patient was withdrawn from the study because of a rash. In two patients the disease flared, once with concomitant hypercalcemia. Tamoxifen is a useful agent for advanced breast cancer even in some patients with visceral disease.
Cancer Chemother Pharmacol 1979
PMID:Phase-II trial of tamoxifen in advanced breat cancer. 53 27

Twenty-five patients with measurable metastatic breast cancer and assays for estrogen receptor (ER) were studied. Of the 16 ER positive patients on anti-estrogen therapy, one had complete disappearance of all tumor for seven months and seven patients had more than 50% reduction in their measurable tumor for an average duration of 8.8 months. Seven other ER positive patients had stabilization of their tumors for an average interval of 8.4 months. Only one of the 16 ER positive patients progressed promptly. Conversely there was only one partial response in the nine ER negative patients and only two ER negative patients had stabilization of disease. Six out of nine ER negative patients progressed promptly. Correlation existed between the duration of response and absolute estrogen receptor level of the tumor. There may be a positive correlation between the response to antiestrogen therapy and response to endocrine ablation but prospective studies must be done to further define the role of antiestrogens in this regard.
Cancer 1978 Mar
PMID:The use of antiestrogens tamoxifen and nafoxidine in the treatment of human breast cancer in correlation with estrogen receptor values. A phase II study. 63 66

The reason for estrogen independence of C3H mouse mammary tumors has been sought in the initial steps of estradiol action. The characteristics of the estrogen receptors were similar to those observed in estrogen-responsive tissues: high affinity and binding specificity, DNA binding and 8S sedimentation constant as shown by sucrose gradient centrifugation. Their concentration averaged 18.5 +/- 3.5 (S.E.) fmol/mg cytosol protein in the cytosol and 3.5 +/- 1.0 fmol/mg cytosol protein in the KCl nuclear extract. The nuclear translocation of the cytosol receptor was investigated with the use of biopsy and in vivo injections of radioactive estradiol. No nuclear translocation of estrogen receptor could be ascertained with the dextran-coated charcoal assay since the free and nonspecifically bound estrogen conjugate(s) were also assayed by this technique. However, when the estrogen-receptor complexes were estimated by more specific methods such as protamine sulfate or hydroxylapatite precipitations, the estrogen receptor translocation into the nucleus was clearly shown. We therefore conclude that the estrogen independence of C3H mammary tumors cannot be explained by a defect in the two initial steps of the mechanism of action of estradiol, namely, cytosol binding and nuclear translocation of receptors.
Cancer Res 1978 Jun
PMID:Nuclear translocation of the estrogen receptor in autonomous C3H mouse mammary tumors. 64 90

This study was undertaken to define the incidence and concentration of uncharged nuclear estrogen receptors (RN) in human breast cancer. The concentrations of RN and cytoplasmic uncharged receptor were determined on sucrose gradients following a 4-hr incubation at 4 degrees with 1.6 nM 17 beta-[3H]estradiol in 139 tumor specimens from 137 patients. RN was extracted from washed nuclear pellets in buffer containing 0.4 M KCl. The receptor molecule extracted had a high affinity for 17 beta-[3H]estradiol (Kd = 0.9 to 7.6 nM) and was specific for estrogen. The possibility of artifact due cytoplasmic contamination of the nuclear fraction or high-ionic-strength-induced exchange of charged nuclear receptors was rendered unlikely by validation experiments performed with pooled tumor tissue. Significant amounts of cytoplasmic uncharged receptor (greater than 7 fmol/mg protein) were found in 63.3% of the tumors. Similar significant amounts of RN were found in 29.5% of the tumors. Significant amounts of RN in the presence of undetectable cytoplasmic uncharged receptor were found in 2.9% of the tumors. The percentage of tumors that contain significant amounts of RN is approximately the same percentage of estrogen receptor-positive tumors that do not respond to ablative therapy.
Cancer Res 1978 Jul
PMID:Uncharged nuclear receptors for estrogen in breast cancers. 65 33

The concentration of estrogen receptor (ER) in a human breast tumor is a critical variable predicting the response to endocrine therapy and the course of the disease. Since many tumor specimens are quite small, a reliable and simple ER assay requiring a minimum of tissue is desirable. We here describe a hydroxylapatite assay for ER that (a) requires only a single, saturating concentration of [3H]estradiol, (b) agrees with more complex multiple-concentration assays and with the standard dextran-coated charcoal assay at normal protein concentrations, (c) is far more reliable than the latter at low protein concentrations, and (d) can be adapted to an accurate and reliable ER microassay requiring less than 50 mg of tissue.
Cancer Res 1978 Aug
PMID:A hydroxylapatite micromethod for measuring estrogen receptor in human breast cancer. 66 18

The effect of 17beta-estradiol on an estrogen receptor-positive human breast cancer cell line (MCF-7) was studied. Low concentrations (10(-9) M) of 17beta-estradiol enhanced the rate of cell proliferation; the overall cell cycle time was shortened; and the proportion of cells in the S phase increased. Higher concentrations (10(-7) M) suppressed proliferation and slightly decreased the proportion of the cells in DNA synthesis. When combined with 1-beta-D-arabinofuranosylcytosine, an S-phase-specific chemotherapeutic agent, 10(-9) M 17beta-estradiol enhanced cell killing. This enhancement was not observed with 10(-7) M 17beta-estradiol. Kinetic changes caused by hormones have profound implications in clinical therapy, since the efficacy of cycle active agents may be altered.
Cancer Res 1978 Aug
PMID:Proliferation kinetics of a human breast cancer line in vitro following treatment with 17beta-estradiol and 1-beta-D-arabinofuranosylcytosine. 66 30

Nine human breast cancer cell lines in permanent tissue culture and currently available to researchers have been assayed for their content of cytoplasmic estrogen receptors, progesterone receptors, androgen receptors, and glucocorticoid receptors, as well as for the presence of unfilled or hormone-filled nuclear estrogen receptors. Receptor distribution varied considerably among the nine lines and differed from the expected distribution predicted from solid tumors. We find that estrogen receptor, when present, is usually localized in the nucleus as unfilled nuclear estrogen receptor. Progesterone receptor is correlated with presence of unfilled nuclear estrogen receptor. Glucocorticoid receptors are ubiquitous; they were found in all cell lines tested. The distribution of androgen receptor and progesterone receptor differed, suggesting that these proteins are dissimilar.
Cancer Res 1978 Aug
PMID:Steroid receptor analyses of nine human breast cancer cell lines. 66 41

The influence of steroid hormone receptors on response rate to cytotoxic chemotherapy in 70 patients with metastatic breast cancer was determined in a retrospective study. We have previously reported that 34 of 45 patients with tumors containing low or absent estrogen-receptor values had objective responses to chemotherapy while three of 25 patients with positive estrogen-receptor tumors responded. In the present study, 22 of 34 patients with low or absent progesterone-receptor tumors had an objective response to cytotoxic chemotherapy, while none of eight patients with a positive progesterone-receptor tumor responded (P less than 0.05). Patients having tumors with a negative estrogen receptor and a negative progesterone receptor had a response rate of 88% (21 of 24 patients). There were three patients whose tumors were estrogen-receptor negative but progesterone-receptor positive; none had a response to chemotherapy. Chemotherapy response was not associated with the presence or absence of either androgen or glucocorticoid receptor. We conclude that progesterone-receptor values in addition to estrogen-receptor status may prove to be important correlates of response to cytotoxic chemotherapy in metastatic breast cancer. Androgen- and glucocorticoid-receptor analyses are not helpful in predicting response to chemotherapy.
Cancer Treat Rep 1978 Sep
PMID:Association between steroid hormone receptors and response rate to cytotoxic chemotherapy in metastatic breast cancer. 68 73

As an approach to the mechanism of the nuclear translocation of estrogen receptor, the estradiol nuclear receptor (RN) of lamb endometrium was extracted with micrococcal nuclease at 2--4 degrees and compared to the "native" 8S and to the Ca2+-transformed cytosol receptors. After extensive digestion of chromatin, giving up to 10% perchloric acid-soluble DNA and a majority of nucleosome monomers, up to 80% of the RN was extracted and under low ionic strength. This RN was found to be completely different from the partially proteolyzed Ca2+-transformed cytosol receptor. It migrated with a sedimentation constant of 4 and 6 S. The Stokes radius of the predominant form as determined by ACA 34 chromatography was 5.3 nm. The calculated apparent molecular weights were 130,000 and 90,000, respectively. The RN was able to bind DNA and was eluted from a diethylaminoethyl cellulose column at 0.23 and 0.30 M KCl. We conclude that the mechanism proposed by Puca et al., according to which the Ca2+-transformed cytosol receptor is split by a Ca2+ receptor-transforming factor into a smaller form able to cross the nuclear membrane, is very unlikely.
Cancer Res 1978 Nov
PMID:Comparison between different forms of estrogen cytosol receptor and the nuclear receptor extracted by micrococcal nuclease. 69 61


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