Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
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.
 ...
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.
 ...
PMID:[The antiestrogen tamoxifen in advanced breast cancer (author's transl)]. 677 66

Plasma cortisol, 17-hydroxyprogesterone (17-OH-P), progesterone, FSH, LH and prolactin were determined by RIA, in 14 cancer patients without metastases aged between 40 and 74 years (6 cases of breast cancer: T123, N01, M0 and 8 with other forms of cancer). The cancer patients were investigated: (A) under basal conditions, (B) after three days' adrenal suppression by dexamethasone, 3 mg/day and (C) immediately after local radiation therapy (4500 rads). The basal mean hormonal values in these patients showed increased cortisol, decrease 17-OH-P and normal values of progesterone, FSH, LH and prolactin. Plasma cortisol was significantly reduced by adrenal suppression with a percentage reduction of 19.44 without differences between breast cancer patients and patients with other forms of cancer; adrenal suppression induced an increase of 17-OH-P only in male cancer patients. The only significant hormonal changes after local radiation therapy were increased plasma 17-OH-P values in both female and male cancer patients. A second group investigated in the present study consisted of 11 patients (6 castrated and 5 postmenopausal women) with metastatic breast cancer and presented increased plasma cortisol values, decreased 17-OH-P values, and a great scatter in the estrone values, some of them being very high.
 ...
PMID:Adrenal function in early and metastatic breast cancer: dexamethasone suppression of plasma cortisol. 678 44

Serum prolactin levels were elevated above the range seen in normal male subjects of 7 of 11 patients with non-seminomatous testicular tumours, particularly in patients with metastatic disease. In contrast, the mean prolactin level in patients with seminomas was not significantly different from normal, and only one of eight patients had a serum prolactin concentration beyond the normal range. In two subjects with non-seminomatous testicular tumours serial measurements of prolactin and chorionic gonadotrophin showed a striking parallelism and accurately predicted clinical progress. Serum prolactin may be a useful additional tumour marker in patients with non-seminomatous testicular tumours.
 ...
PMID:The serum prolactin level in testicular tumours--a new tumour marker? 693 51

In this study, various serum hormone levels were determined in patients with metastatic testicular germ cell tumours. Raised LH levels, due to a cross reaction with hCG in the radioimmunoassay, were observed in 20 out of 29 patients with active disease and were mainly caused by gonadotrophin production in the tumour tissue. Increased LH levels were frequently observed in the patients with non-seminomatous tumours, but were also found in 4 (out of 6) patients with metastatic seminoma. One should, however, preferably use a specific hCG radioimmunoassay in order to measure tumour hCG as a tumour marker with a high diagnostic accuracy. In patients with active disease despite ongoing combination chemotherapy which included LH suppressing medication, serum testosterone remained above 6 nmol/l in 11 out of 16 patients. These patients remained sexually potent, while testosterone values below 6 nmol/l usually were combined with sexual impotence in patients during combination chemotherapy. These data strongly suggest that the tumour hCG has a biological activity, stimulating the remaining testis to increased testosterone secretion in these patients. The serum E2-17 beta levels were slightly to moderately increased in half of the patients with metastatic disease. Markedly increased serum E2-17 beta levels (> 0.30 nmol/l) and very high prolactin values (> 32 micrograms/l) were observed only in patients with high LH levels (> 9.5 micrograms/l) and a large tumour burden. These observations indicate that E2-17 beta and prolactin determinations are of minor value for early detection of tumour manifestations. Serum FSH cannot serve as a tumour marker in patients with testicular germ cell tumours.
 ...
PMID:Endocrinological studies in patients with metastatic malignant testicular germ cell tumours. 719 65

64% of all patients with newly diagnosed prostatic carcinoma present with metastases. Hormone application with or without orchiectomy appears to be the adequate form of primary treatment. The most common therapeutic modality is estrogen administration, which has, however distinct disadvantages: The patient is protected up to 5 years only, there is a 27% cardiovascular mortality, it induces a prolactin surge, and is immunosuppressive. Phase III-studies of the EORTC and VACURG have demonstrated that medroxyprogesterone acetate and cyproterone acetate parallel the effectiveness of estrogens. In a phase II-trial adjunctive bromocriptine was found to be necessary to suppress estrogen or antiandrogen induced hyperprolactinemia. The following concept is derived: In disseminated untreated prostatic cancer estrogens or antiandrogens in combination with bromocriptine or high dose injectable gestagens are effective means of primary treatment. Distinct clinical parameters determine the "hormone of first choice". Orchiectomy is reserved for patients with ureteral compression or progressing disease.
 ...
PMID:[Hormone therapy of prostatic cancer (author's transl)]. 719 68

In 32 subjects with histologically and/or cytologically verified prostatic cancer the hormonal pattern was studied by assaying 18 plasma and urinary hormones or groups of hormones. The tumours were classified according to the UICC classification system and the hormone values were correlated to the local extent of the tumour (T classification), the presence of metastases (M classification) and the differentiation of grade (G classification). It was found that patients with metastases had significantly higher plasma oestradiol and lower testosterone/oestradiol and testosterone/oestrone plus oestradiol ratios as compared to those subjects without metastases. In subjects with moderately or poorly differentiated tumours plasma oestrone + oestradiol was significantly higher and the testosterone/oestrone + oestradiol ratio was significantly lower than in the subjects with well differentiated tumours. In the various TNM classification groups no obvious trends were found with regard to urinary hormones and no significant differences between the groups for plasma FSH, LH, prolactin, progesterone and cortisol were observed. It is concluded that in more advanced cases with metastatic cancer and when tumours are less well differentiated the androgen/oestrogen ratio may be decreased. These alterations have no diagnostic significance because of greater overlapping of individual results between the various groups of patients.
 ...
PMID:Hormonal pattern in prostatic cancer. I. Correlation with local extent of tumour, presence of metastases and grade of differentiation. 730 85

Other indicators of hormone sensitivity, besides estrogen receptor (ER) content, such as response to oophorectomy, antiestrogens, prolactin suppression, and correlation with progesterone receptors (PR), were evaluated in the hope of further improving selectivity and response of patients undergoing endocrine ablation for metastatic breast cancers. 225 patients have undergone full endocrine ablation in the last 30 years at this hospital, 208 by adrenalectomy and 17 by hypophysectomy. 206 of these patients could be retrospectively reviewed, and of these there were objective responses to therapy in 50% of patients. ER analyses were performed in 1 or more breast cancer specimens in 113 of these patients. ER study showed that a patient who was ER+ and responded to a functional test of endocrine sensitivity had a 70-80% chance of also benefiting from adrenalectomy or hypophysectomy. Conversely, patients with absent or unknown hormone receptors who failed therapeutic trials of endocrine sensitivity had little or no chance of responding to major ablation; these cases are best treated with multiagent chemotherapy. The value of sequentially treating selected patients with endocrine manipulation in addition to chemotherapy was also studied. Patients who failed to respond to endocrine manupulation survived slightly over 2 years on chemotherapy, whereas patients who responded to major ablation lived with metastases an average of 4 years, whereas complete responders lived with metastatic disease an average of 6 years. By life table analysis, total survival of ER+ vs. ER- patients as well as responders vs. nonresponders was highly significant
 ...
PMID:Endocrine ablation for metastatic breast cancer: a reappraisal of hormone receptors. 739 80

A 59-year-old male patient was transnasally operated on because of a pituitary adenoma with hypopituitarism. A second operation and X-ray therapy followed a half year later due to recurrent tumor. Both neoplasmas were classified as sparsely granulated prolactin cell adenomas. Immunohistochemical studies revealed strong immunoreactivity for prolactin and FSH in the tumor cells of both the pituitary adenoma and the recurrent tumor. Two years later the prolactin plasma levels were extremely elevated. A tumor in the liver was identified. Biopsy revealed a solid endocrine tumor containing prolactin by immunohistology. Due to structural and immunohistological similarities this tumor could be identified as a metastasis of the pituitary tumor. After 5 months of therapy the patient died from thrombembolism. Post-mortem studies confirmed the diagnosis of a metastasizing prolactin-secreting pituitary carcinoma. Only six similar cases have been reported in the literature. Our case report confirms the experience with 35 definite pituitary carcinomas reparted in the current literature: malignant pituitary tumors develop after pituitary surgery and can be identified not from the pituitary tumor, but only from its metastases.
 ...
PMID:[Prolactin producing hypophyseal carcinoma. Case report of an extremely rare metastatic tumor]. 747 9

NK cell activity was measured in 24 patients with untreated prostate cancer (11 subjects with localized disease, D0, and 13 patients with stage D tumor) and 10 healthy controls. In these same subjects serum prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), testosterone, prolactin and cortisol concentrations were assessed. The data obtained were correlated with both tumor spread (localized vs disseminated disease) and grade (well-differentiated cancer, G1, vs moderately and poorly differentiated carcinoma, G2 and G3). In patients with stage D0 cancer mean NK activity (33.0 +/- 10.6) was virtually identical with the mean value recorded in healthy men (34.5 +/- 7.1), while in subjects with stage D1-D2 disease NK activity was significantly reduced (11.9 +/- 7.1). These findings correspond with our data on treated subjects, in whom NK activity level was found to correlate well with the presence of tumor cells in the circulation. In subjects free of malignant tumors but with a chronic disease (diabetes, arthritis, severe rheumatic disorders) mean NK activity was clearly reduced (5.7 +/- 1.5). The use of NK activity data as a probe for tumor metastases was found to be statistically as reliable as was the application of the PSA serotest (but not serum PAP concentrations). None of the measured hormonal parameters correlated well with tumor stage. Both testosterone and prolactin serum concentrations were found to be lower in the G2 and G3 cancer group than in well-differentiated (G1) tumors, in accordance with the published literature.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Comparison between NK cell activity and prostate cancer stage and grade in untreated patients: correlation with tumor markers and hormonal serotest data. 768 Dec 42


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