Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper reviews the recent laboratory findings about the nonsteroidal antiestrogen, tamoxifen, and its more potent major metabolite, monohydroxytamoxifen. Both compounds stimulate progesterone receptor synthesis in the rat uterus, and there is an inhibition of cell division in the uterine luminal epithelial cells. The effects of tamoxifen in vivo may be a result of the net effects of the parent compound and monohydroxytamoxifen. In rats with dimethylbenzanthracene (DMBA)-induced rat mammary carcinomata, young tumors that are estrogen receptor- and progesterone receptor-rich respond more favorably to tamoxifen that do older estrogen receptor- and progesterone receptor-poor tumors. However, the antitumor effect of tamoxifen in the DMBA-induced rat mammary carcinoma model is probably a result of the blockade of tumor estrogen receptors, a reduction in circulating gonadotropins, lower circulating estrogen levels, and lower circulating prolactin levels. The 30-days treatment of rats with tamoxifen 30 days after DMBA resulted in a dose-related decrease in the appearance and numbers of mammary tumors; however, only continuous therapy maintained animals in a tumor-free state. Monohydroxytamoxifen was a less-potent antitumor agent, probably because it is cleared from the rat more rapidly than tamoxifen. The present laboratory findings support the clinical use of tamoxifen as a treatment of endometrial carcinoma and the resultant metastases and as an adjuvant therapy after surgery for breast cancer.
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PMID:Pharmacology of tamoxifen in laboratory animals. 677 7

The antiestrogenic agent tamoxifen was evaluated in 17 pre- and 103 postmenopausal women with recurrent or metastatic breast cancer at two dose levels (2 and 3 x 10 mg daily). Dose-related differences in the results were not observed. Altogether 49.2% of these patients responded to therapy (10% complete remissions, 9.2% partial remissions, 30% no change). While a response rate of 52.5% was found in the postmenopausal group, the rate was markedly worse in premenopausal women (29.4%). In postmenopausal patients there was a poorer remission rate in older women. Regarding the dominant site of lesions, the best results were achieved in patients with lung and pleural metastases, followed by soft tissue metastases. Patients with a disease-free interval of more than 100 months responded better to therapy than those with a shorter interval. Long-term results were much more favorable in patients who primarily responded to tamoxifen than in nonresponders. As the most valuable prognostic criterion, the hormone receptors were assayed. 75% of the estrogen receptor (ER) and progesterone receptor (PgR) positive and 55,6% of the ER-positive and PgR-negative patients derived benefit from this treatment in contrast to only 19% of the ER- and PgR-negative women. Plasma levels of estradiol, progesterone, testosterone, and FSH were not changed by tamoxifen, but average cortisol and prolactin concentrations were altered significantly. A short-time increase of the prolactin level 2 weeks after onset of tamoxifen treatment and a decrease thereafter also seem to be good prognostic signs. Side effects were few and did not occur more severely or frequently in the higher dose group.
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PMID:[The antiestrogen tamoxifen in advanced breast cancer (author's transl)]. 677 66

Progesterone receptor was measured in eight samples of renal cell carcinoma, nine samples of normal renal tissue, and one sample of melanoma tissue. Progesterone receptor was identified in all samples, with the exception of one renal cell carcinoma. Three patients, all with receptor-positive tumors, were treated with medroxyprogesterone acetate for metastatic disease. In one of these patients there was a partial objective response to treatment. Further research regarding progesterone receptor in renal cell carcinoma is indicated.
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PMID:Measurement of progesterone receptor in human renal cell carcinoma and normal renal tissue. 683 34

Bartholin's gland carcinoma is an uncommon disease representing 0.1% of all female genital malignant neoplasms. Five Bartholin's gland adenocarcinomas were selected by the criteria of Chamlian and Taylor. Three patients died from metastatic disease within four years; two are free of apparent disease 14 months and 13 years, respectively, after initial diagnosis. Poor prognosis was associated with large tumor size, poor histopathologic differentiation, and lymph node involvement. Transmission electron microscopy verified the glandular nature of the poorly differentiated lesions. All five tumors demonstrated junctional complexes, abundant rough endoplasmic reticulum, secretory vacuoles, and glandular formation. Low levels of estrogen receptor and moderate levels of progesterone receptor were present in the one case measured. Endogenous peroxidase, and inducible enzyme in estrogen-sensitive tissues, was observed in two of the five tumors.
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PMID:Adenocarcinoma of Bartholin's gland. 689 95

The fractions of cells in the different phases of the cell cycle were determined by flow cytometry in 70 human breast tumors and six human benign breast tissues. This procedure showed that 44% of the tumors and none of the benign tissues were aneuploid as determined by mixing experiments using normal peripheral blood as a standard for DNA content per nucleus. The mean percent S-phase fraction (% S) values +/- S.D. for benign and malignant tissues were 6.9 +/- 1.6 and 13.7 +/- 6.5, respectively. By our procedure, aneuploid tumors seem to have significantly higher mean % S value than do diploid tumors. Breast cancer tissue which contained steroid receptors had a mean % S value of 11.3, while those tumors which had neither the estrogen nor progesterone receptors had a mean % S value of 17.1 (p less than 0.01). The estrogen receptor status had a better inverse relationship to the cell kinetic data than did the progesterone receptor status. The use of molecular forms of the steroid receptor was of some assistance in improving the inverse relationship between cell kinetics and steroid receptor status. A trend was observed between lack of steroid receptors and higher probability of the tumor being aneuploid. From the limited clinical data, there was no relationship between cell kinetic and aneuploid data with respect to nodal status, metastatic disease, and menopausal status. The possible use of these data is discussed.
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PMID:Relationship of steroid receptor, cell kinetics, and clinical status in patients with breast cancer. 702 Sep 31

Similarities between endometrial and mammary tissue as targets for ovarian hormones indicate that measurements of estradiol and progesterone receptor (RE and RP) levels may be as useful in endometrial cancer as they are in breast cancer for the prediction of responses to treatment with steroids and antiestrogens. Receptor levels cannot be inferred from the degree of differentiation of the endometrial tumors, although RP values are lower in poorly differentiated adenocarcinoma. Current studies aim to relate RP levels to objective remissions of metastases after progestin therapy, and attempts are being made to increase RP with tamoxifen before treatment with progestins or assaying for RP. In vitro studies aim to elucidate fundamental problems related to the action of steroids on the tumors, e.g., mechanism by which receptors mediate the effects of pharmacologic doses of drugs, factors that regulate receptor levels, and homogeneity in the distribution of receptors in tumor cell populations.
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PMID:Hormone receptors in endometrial cancer. 702 68

The presence of progesterone receptors was found to be associated with a favorable prognosis in 98 patients with primary breast cancer. The occurrence of metastases was 3.6 times less probable in patients with progesterone receptor-positive tumors than in patients with progesterone receptor-negative tumors. There was also an inverse relationship between the concentration of progesterone receptor and the frequency of metastases. However, there was no statistical correlation between frequency of local recurrences and progesterone receptor content of the tumor. In patients displaying clinical or histological criteria of gravity, the presence of progesterone receptors allowed us to define subgroups with good prognosis. Thus, in women with progesterone receptor-positive cancers, metastases had occurred at 18 months, in only 5% of the 39 Grade III cancers and in none of the 25 cases with invaded axillary nodes. Measurement of estradiol receptor (105 patients including the previous 98 patients) was found to be less effective for guiding the prognosis of early breast cancer. Combined evaluation of estradiol and progesterone receptors did not provide any more information than did the determination of progesterone receptor alone.
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PMID:Relationship of presence of progesterone receptors to prognosis in early breast cancer. 742 48

Estradiol receptor (RE) and progesterone receptor (RP) contents of primary human breast tumors are markedly influenced by histologic grade of the tumor. As the tumor becomes more anaplastic, there is an increase in the proportion of RE negative, RP negative tumors at the expense of the RE positive, RP positive group. Evidence is presented to suggest that some RE positive, RP negative tumors from postmenopausal women lack RP because of estrogen deficiency. The inclusion of RP assays increases the clinical usefulness of receptor assays in predicting response to hormone therapy for the advanced disease. Preliminary evidence suggest that RE and RP assays on the primary tumor may indicate the hormone sensitivity of subsequent metastatic disease.
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PMID:Analysis of estradiol and progesterone receptors in early and advanced breast tumors. 744 27

CD44 designates a group of closely related cell-surface proteins generated by alternative splicing. We have previously shown that splice variants carrying sequences encoded by exon v6 are preferentially expressed in metastatic animal cancer cell lines and that they confer metastatic behaviour on non-metastatic animal tumour cell lines. In this study we set out to assess the expression of CD44 epitopes specific for variant exon sequences in human breast cancer and their potential for determining prognosis. We used affinity-purified polyclonal sera and four monoclonal antibodies raised against the human homologues of CD44 variant exon sequences to investigate the presence of CD44 on 100 primary invasive breast tumours, 12 local recurrences, 18 lymph node metastases, and normal tissue controls. Whereas normal mammary ductal epithelial cells and cells derived from hyperplastic lesions do not express CD44 variant exons, expression of v3, v5, and v6 epitopes was found in most tumour samples. The DIII (exon v6) epitope was present in 84% of the primary tumours and in 100% of axillary lymph node metastases and local recurrences. The presence of these CD44 epitopes is correlated with poor overall survival. 15 patients with exon-v6-negative tumours had good survival compared with 76 patients with exon-v6-positive tumours (p = 0.005; log rank test). Multivariate analysis showed that the CD44 epitope encoded by exon v6 was a good marker for prognosis independent of progesterone receptor, lymph node status, tumour size, and grade.
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PMID:CD44 variant exon epitopes in primary breast cancer and length of survival. 753 42

For quantificative determination of ERBB2 gene amplification in archival human carcinoma specimens we have developed a rapid, non-radioactive approach, which is based on the differential polymerase chain reaction (PCR) and fluorescent DNA technique. Sequences from the ERBB2 gene and from a single-copy reference gene were amplified simultaneously by PCR, in which one of each primer pair was fluorescently labelled. PCR products were separated by polyacrylamide gel electrophoresis in an automated DNA sequencer and directly quantified after laser activation and emission scanning using appropriate software. This fluorescent differential polymerase chain reaction (fd-PCR) method was used for quantificative determination of ERBB2 gene amplification in 195 formalin-fixed, paraffin-embedded breast carcinoma tissues. ERBB2 gene amplification was found in 52 (26%) of these tumors and correlated significantly with tumor size, absence of estrogen receptor (ER) and pS2 expression, but not with absence of progesterone receptor (PR) or presence of epidermal growth factor receptor (EGF-R) expression, lymph-node metastases or grading. In univariate analysis, ERBB2 gene amplification showed no significant correlation with clinical outcome, either in the whole population or in the subgroup defined by positive axillary lymph-node metastases. However, within the node-negative subgroup, patients with ERBB2 gene amplification had significantly decreased relapse-free survival and overall survival (p < 0.05). The fd-PCR assay is a valuable tool for determination of amplification of ERBB2 gene as well as further oncogenes. In this way, more detailed information about individual tumor biology may be acquired by a routine assay.
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PMID:ERBB2 gene amplification detected by fluorescent differential polymerase chain reaction in paraffin-embedded breast carcinoma tissues. 759 Dec 99


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