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)

The indications for and the results of hypophysectomy for advanced cancer of the breast or prostate gland are reviewed. The technic of open microsurgical transsphenoidal hypophysectomy is described. Since the metabolism of some breast cancers is influenced by estrogenic hormones, the major effect of hypophysectomy seems to be the complete suppression of estrogen production by the gonads and adrenal glands by removal of gonadotropin and ACTH, respectively. Other specific substances, such as growth hormone or prolactin, may also be factors. In cases of prostate cancer which relapse after castration, the adrenals seem to elaborate a significant amount of extradgonadal androgen. Hypophysectomy removes the source of ATCH and thus stops androgen production by the adrenal glands. Other hormones may also be important. In premenopausal patients with advancing cancer of the breast, oophorectomy should be the initial procedure. Most patients after a previous favorable response to oophorectomy get a subsequent objective improvement from hypophysectomy. In postmenopausal patients the effects of hormone therapy should 1st be tried. Many patients responding favorably to hormone therapy will also be benefited later by hypophysectomy. Remission rates are higher in older women. However, hypophysectomy should be carried out relatively early to obtain a useful remission. About 25% of those not responding to other methods will obtain a remission following hypophysectomy. Along interval after the mastectomy before metastases occurs is a favorable prognostic sign. While bony metastases respond best, other sites of metastases do not contraindicate the operation. Most patients with prostatic metastases obtain relief after hypophysectomy, even some of those who have not been benefited by other methods. Advanced age alone is not a contraindication. A preoperative evaluation should be done including a series of endocrine studies. Open microsurgical transsphenoidal hypophysectomy is considered the operation of choice. Complete removal of the gland is accomplished with less disturbance to the patient than an intracranial operation. General anesthesia is used. After the operation tests for pituitary reserve are repeated and a maintenance regimen of hydrocortisone prescribed. Thyroid replacement therapy is often needed. Subjective remissions are more common than objective ones, particularly relief of pain. This operation was done on 20 men with metastatic cancer of the prostate and 23 women and 1 man with metastatic cancer of the breast. Of the prostate cases, 3 patients died during the early postoperative period. Of the other 17, there have been 7 deaths from the cancers after 1-7 months. Of the 23 breast cases, severe body pain was the indication for the operation. Relief occurred in 19 (83%). There have been 7 deaths from the cancers. Hypophysectomy does not predispose to or lead to alterations in emotional state or mental function. Others with larger series of cases have reported that those responding favorably have lived an average of 25.8 months while average survival of those not so responding has been only 5.6 months.
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PMID:Hypophysectomy in the treatment of disseminated carcinoma of the breast and prostate gland. 127 14

Among 288 patients with prolactinoma (aged 12-62 years; 242 women), 27 were diagnosed as resistant to bromocriptine as their plasma prolactin (PRL) levels remained elevated despite long-term (3 months or more) treatment at high doses (> or = 15 mg daily). These 18 women and 9 men, aged 29 +/- 9 years (mean +/- SD, range 13-50), followed-up for 8 +/- 4 years, had microadenomas (n = 6) or macroadenomas. They were treated by dopamine agonists alone (n = 6) or associated with surgical or radiation therapy. In 8 cases repetitive surgical treatments were necessary. Among the 24 patients who were treated with the nonergot dopamine agonist CV 205-502 after unsuccessful bromocriptine treatment, half of them (9 women, 3 men) resumed normal PRL levels on doses ranging from 0.15 to 0.45 mg/day. Despite daily doses of CV 205-502 from 0.3 to 0.525 mg, the remaining patients were not normalized by this drug which did not prevent tumor growth in 4 of them. Two patients died from invasive cerebral extensions of their tumor and a third had vertebral metastases with positive anti-PRL immunostaining. It is concluded that bromocriptine-resistant prolactinomas represent the most severe aspect of this disease and that a more powerful dopamine agonist like CV 205-502 is effective in only a fraction of these patients.
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PMID:Prolactinomas and resistance to dopamine agonists. 130 23

Natural killer (NK) cell activity was studied together with tumor marker serotests (PSA, PAP) and blood testosterone, estradiol, cortisol, and prolactin concentrations in treated prostate cancer patients. NK cell activity data were correlated with tumor stage (stage D0 + D1 versus stage D2) and showed statistically insignificant differences. Both tumor progression and stabilization of metastatic disease, triggered by the application of more appropriate therapy in progressive subjects, yielded low NK activity data. By contrast, normal NK activity was found during both partial remission of stage D2 tumor and stabilization of the same disease, after an initial period of tumor remission. Differences between NK activity data from the aforementioned two groups are statistically significant (P less than 0.01). In subjects examined, the application of NK activity assay to those with advanced disease reflected changes in the outcome of the treatment more closely than it did routine tumor marker assessment. The activity of NK cells seems unaffected by changes in basal blood estradiol, cortisol, testosterone, and prolactin concentrations that occur during therapy with pharmacological agents (estradiol, cyproterone acetate, diethylstilbestrol, and flutamide) and during surgical castration. The reported NK activity recordings in treated prostate cancer patients might be indicative of the presence of tumor cells in the circulation. If this holds true, the measurement of NK activity would appear to furnish urological oncology with a new tool for early, rapid recognition of progressive metastatic tumors.
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PMID:NK cell activity in treated prostate cancer patients as a probe for circulating tumor cells: hormone regulatory effects in vivo. 138 13

Breast cancer is the most common malignant tumor among women, comprising an estimated 24% of all cancer cases and 18% of all cancer deaths. At least half of the patients with primary breast cancer will ultimately die by metastatic disease. The tumor characteristics, the natural course of the disease and the response to therapy vary strongly. A number of recently detected cell biological parameters such as oncogenes/suppressor genes, growth factors and secretory proteins are more or less important prognostic factors, because they influence the characteristics and behavior of a tumor with respect to metastatic pattern, extent of cellular differentiation, growth rate and response to treatment. However, there is no clear consensus how best to identify patients at high or low risk. In our experience c-myc amplification and pS2 protein are strong prognosticators for relapse rate, while in advanced disease (apart from a negative estrogen/progesterone receptor/pS2 status) amplification of HER2/neu is a good prognosticator for failure to endocrine therapy. In the diagnosis of breast cancer, in vivo imaging of tumors by labeled hormones or other factors also forms a new development which might have implications for treatment too. With respect to treatment both endocrine and chemotherapy can cure a minority of patients with micrometastases, but in patients with advanced disease only a prolongation of (progression-free) survival can be reached. Response rates decrease with increasing tumor load. In the past decade a number of interesting new endocrine agents has been developed such as new (pure) (anti)steroidal agents, vitamins, aromatase inhibitors, analogs of peptide hormones, prolactin inhibitors and growth factor antagonists. However, less is known on the (potential) interaction between hormones, chemotherapeutic agents, retinoids, cytokins, growth factor antagonists and irradiation. Rapid detection of new powerful combination therapies are needed to improve treatment results during the nineties.
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PMID:Clinical breast cancer, new developments in selection and endocrine treatment of patients. 144 97

During a routine long-term drug safety study, lasting approximately 2 1/2 yr, male Wistar rats, treated with a prolactin-inhibiting compound, developed an excess of Leydig cell tumors (LCTs). Most tumors were typical for the rat but a small number showed an unusual variation and some appeared malignant. The variation consisted of glandular and/or tubular structures within the tumor mass which occasionally anastomosed and contained an eosinophilic periodic-acid Schiff (PAS) positive material. In a few of these variants, malignant features such as cellular atypia, capsular, and lymphatic invasion and necrosis were seen. No metastases were detected. Detailed morphological and immunohistochemical investigations were conducted in order to establish the cell of origin of these variants. Glandular/tubular structures were found to stain with varying intensity for vimentin and cytokeratin, but were always negative for beta-tubulin. The results indicated that the cell of origin of these LCT variants was indeed the Leydig cell and that glandular and/or tubular structures within LCTs represented a form of Leydig cell metaplasia.
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PMID:Morphologic and immunohistochemical characterization of Leydig cell tumor variants in Wistar rats. 172 33

Pituitary adenomas rarely are metastatic. Extracranial visceral metastases of prolactinomas were not previously reported. The authors report a case of a 34-year-old man with a prolactin-producing pituitary carcinoma and histologically proven lung metastases. Pathologic examination of the pulmonary spread included electron microscopy and immunohistochemistry; these confirmed prolactin production by the tumor. The patient's presentation at initial diagnosis, disease recurrence, clinical course, management, and response to therapy (with its theoretic basis) are detailed. Despite the use of dopamine analogues (to tolerance and in combination), there was documented intracranial and extracranial disease progression. Possible future therapeutic maneuvers are discussed.
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PMID:Prolactin-producing pituitary carcinoma with pulmonary metastases. 189 60

In order to study the growth kinetics of breast tumours during long-term hormonal withdrawal, we developed a transplantable, invasive mammary carcinoma EMR-86 that originated in a female WAG/Olac rat bearing a subcutaneously implanted oestrogen pellet (EP). Outgrowth of transplanted tumours occurs only in the presence of an EP, and metastases are formed in lungs and regional lymph nodes. Subsequent EP removal induces rapid regression. However, tumours do not disappear completely, as small nodules persist. These dormant tumour remnants can be restimulated even after long periods. Because EP-stimulated tumours regressed after treatment with bromocriptine and dormant tumours in non-oestrogenized rats grew out after treatment with perphenazine, prolactin is the major growth-stimulating hormone in this model. Cell kinetics in the growing, regressing and dormant phase were studied by immunocytochemical detection of DNA-incorporated bromodeoxyuridine (BrdUrd) in tissue sections. BrdUrd labelling indices decreased from 21.6 +/- 3.0% to less than 1% within 7 days after EP removal. After prolonged hormonal withdrawal (up to 90 days) BrdUrd-labelled tumour cells could always be demonstrated (range 0.4-0.8%), without a concomitant increase in tumour volume. Additional treatment either with bromocriptine or with ovariectomy could not significantly reduce this residual proliferative activity, as demonstrated by continuous BrdUrd labelling experiments. The results indicate that in vivo dormancy may represent a steady state of cell division and cell loss, rather than an accumulation of cells in a non-cycling G0 state.
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PMID:A prolactin-dependent, metastasising rat mammary carcinoma as a model for endocrine-related tumour dormancy. 191 Nov 85

Serum melatonin was determined over 24 hours in 35 patients with breast cancer with either a fresh primary tumor (n = 23) or a secondary tumor (n = 12) and in 28 patients with untreated benign breast disease (controls) having a fibroadenoma (n = 10), fibrocystic mastopathy (n = 14), or other breast diseases (n = 4). Circadian rhythms existed in all groups with acrophases at 2 a.m. A 50% depression of peak and amplitude occurred in the group of patients with primary breast cancer compared with age-matched controls (P less than 0.001, P less than 0.01). The peak declined with increasing tumor size: 27% at Stage T1, 53% at T2 (P less than 0.001), and 73% at T3 (P less than 0.05). In contrast, patients with secondary breast cancer, particularly those receiving antiestrogen therapy, had a melatonin peak similar to controls. These results demonstrated a transient depression of pineal melatonin secretion in primary breast cancer and indicated a dynamic role of the pineal gland in malignancy. To investigate some endocrine effects of a depressed melatonin peak, the 24-hour rhythms of prolactin (PRL) and thyroid stimulating hormone (TSH) were determined in patients with primary breast cancer and compared with patients with secondary breast cancer. The PRL had significant circadian rhythms in both groups; but acrophases occurred at midnight in patients with secondary breast cancer, and there were unusually high concentrations at noon in patients with primary breast cancer. Circadian rhythms were not seen for TSH, but the 24-hour average secretion was depressed by 45% (P less than 0.01) in patients with primary breast cancer. The abnormal concentrations of PRL and TSH in these patients could be due to a depressed melatonin peak normally serving as a central circadian synchronizer and modulator of the secretion of adenohypophysial hormones. Additionally, a positive correlation existed between the nocturnal melatonin peak and progesterone and androgen receptor concentrations in primary tumors indicating a direct involvement of melatonin in the growth control of breast cancer.
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PMID:Stage-dependent depression of melatonin in patients with primary breast cancer. Correlation with prolactin, thyroid stimulating hormone, and steroid receptors. 273 89

1-(3'-Chlorophenyl)-3-[2-(3,3-dimethyl-1-azetidinyl)ethyl] imidazolidin-2-one, zetidoline, a new neuroleptic agent, when incubated with rat liver microsomes was rapidly metabolized to six free (mets B, D, I, L, M and N) and two conjugated metabolites (mets E and F). Sites of the metabolic attack (oxidation) were primarily the aromatic moiety, then the imidazolidinone and the azetidine rings. The metabolites were purified and structures assigned by means of EI-MS, 1H-NMR and chemical synthesis (mets B, D, L and M). The main metabolites, zetidoline, some chemical analogues and a few known dopamine antagonists were tested as in vitro inhibitors of 3H-zetidoline and 3H-spiperone binding to rat striatal membranes, and as in vivo inducers of prolactin release in female rats (inhibition of the estrus cycle). Two zetidoline metabolites, namely 4'-hydroxy zetidoline (met. B) and 5-hydroxy zetidoline (met. L), were found to have both in vitro and in vivo activities comparable to those of the parent drug. Identification of these active hydroxylated metabolites appears important both in the search of new leads of neuroleptics and for designing pro-drugs derivatives with improved pharmacokinetic profiles.
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PMID:Zetidoline metabolism by rat liver microsomes. Formation of metabolites with potential neuroleptic activity. 287 40

Blood levels of prolactin are consistently raised in women who have undergone mastectomy for breast cancer, probably because of the stress of surgery. Since this increase in concentration of a known breast epithelial growth promoter might stimulate proliferation in micrometastatic cells shed at the time of surgery, a pilot study was conducted to try to abolish this effect. 38 patients with suspected operable breast cancer were given either bromocriptine (18) or placebo (20) tablets for 5 days preoperatively and thereafter for 3-10 days. Bromocriptine-treated patients showed significant reductions in prolactin levels and in S-phase fraction of tumour cells within the primary infiltrating carcinoma. There were no major side-effects. Perioperative bromocriptine may provide another approach to adjuvant therapy, possibly combined with endocrine or cytotoxic treatment for patients with axillary nodal metastases.
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PMID:Perioperative bromocriptine adjuvant treatment for operable breast cancer. 289 47


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