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)

Human breast cancer was studied by in vitro techniques on tissue slices and extracts for a specific binding of estradiol and dihydrotestosterone. Estradiol receptors were found in 50 percent of patients in the premenopausal group and in 47 percent of patients in the postmenopausal group. The incidence of receptors in patients with metastatic disease was 32.5 percent. In 18 of 35 patients who were positive for receptor sites a remission was observed after a variety of endocrine treatment regimens. In contrast only 3 patients out of 43 with a negative binding pattern responded to treatment with nafoxidine for a very short time. The best correlation was found in the ovariectomized group. Between the responders and the nonresonders there is no difference in the quantitative receptor content. The same is valid in view of the duration of the remission.
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PMID:Steroid hormone receptors in human breast cancer and clinical correlations. 17 16

166 Sprague-Dawley Rats (148 males and 118 females) submitted to different hormonal conditions were exposed to 3 repeated whole-body irradiations of 14.8 MeV neutrons or sham-irradiated between 50 and 65 days of age (total absorbed doses: 3 x 2 rad and 3 x 8 rad). They were observed for 11 months. In the male group, a small number of tumors was obtained. In the female group, 75 breast neoplasms were scored in 41 of 78 irradiated animals (54 fibroadenomas, 20 adenocarcinomas and 1 fibrosarcoma). A second group of benign and malignant tumors was observed from 200 days on. The neoplastic response to fast neutron fractionated irradiations was increased by pregnancy with subsequent lactation. Estradiol and progesterone receptors were measured in 34 tumor samples. Fibroadenomas (1;5) and adenocarcinomas (1;3) bound labelled steroids. Like in human breast cancer metastases, steroid receptors are found in recurrences only if present in the primary tumor.
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PMID:Mammary carcinogenesis in Sprague--Dawley rats following 3 repeated exposures to 14.8 MeV neutrons and steroid receptor content of these tumor types. 55 71

Breast cancers containing estrogen receptors are responsive to antiestrogen treatment and have a better prognosis than estrogen receptor-negative tumors. The loss of estrogen and progesterone receptors appears to be associated with a progression to less-differentiated tumors. We transfected the human estrogen receptor into the estrogen receptor-negative metastatic breast cancer cell line MDA-MB-231 in an attempt to restore their sensitivity to antiestrogens. Two stable sublines of MDA-MB-231 cells (HC1 and HE5) expressing functional estrogen receptors were studied for their ability to grow and invade in vitro and to metastasize in athymic nude mice. The number and size of lung metastases developed by these two sublines in ovariectomized nude mice was not markedly altered by tamoxifen but was inhibited 3-fold by estradiol. Estradiol also significantly inhibited in vitro cell proliferation of these sublines and their invasiveness in Matrigel, a reconstituted basement membrane, whereas the antiestrogens 4-hydroxytamoxifen and ICI 164,384 reversed these effects. These results show that estradiol inhibits the metastatic ability of estrogen receptor-negative breast cancer cells following transfection with the estrogen receptor, whereas estrogen receptor-positive breast cancers are stimulated by estrogen, indicating that factors other than the estrogen receptor are involved in progression toward hormone independence. Reactivation or transfer of the estrogen receptor gene can therefore be considered as therapeutic approaches to hormone-independent cancers.
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PMID:Activation of estrogen receptor transfected into a receptor-negative breast cancer cell line decreases the metastatic and invasive potential of the cells. 145 45

The effects of hormonal ablation, estrogen, estrogen-derived cytotoxic agent, and estrogen antagonist therapies used clinically were evaluated on in vitro colony formation, in vivo growth, and lymphatic and pulmonary metastasis of the PAIII tumor. Ventral prostatic and seminal vesicle weights were evaluated in the same animals to assess androgen-related responses. Estradiol, estramustine phosphate, and testosterone had no effects on PAIII colony formation in vitro. Castration, hypophysectomy, estradiol benzoate, and estramustine phosphate treatment of PAIII-bearing Lobund Wistar rats produced significant (P less than 0.05) regression of male accessory sex organs. Of these treatments, only hypophysectomy had significant (P less than 0.05) inhibitory effects on primary PAIII growth and lymphatic and pulmonary metastasis. LY117018 [6-hydroxy-2-(p-hydroxyphenyl)benzo(b)thien-3-yl-p-2-(l-pyrrolidin yl)ethoxy phenyl ketone] has antiestrogenic activity but produces no significant agonist responses. LY117018 had no effect upon PAIII colony formation in vitro. Following s.c. implantation of PAIII cells, LY117018 (2.0, 10.0, or 20.0 mg/kg s.c.) had no effect on primary tumor growth in the tail. In vitro LY117018 administration produced marked antimetastatic effects. In a dose-dependent manner, LY117018 inhibited PAIII metastasis to the gluteal (97%) and iliac lymph nodes (88%) (P less than 0.05 for both). LY117018 also maximally inhibited pulmonary metastasis by 86% (P less than 0.05). Maximal regression of 42% for ventral prostatic and 35% for seminal vesicle weights were also seen after LY117018 administration (P less than 0.05 for both). Co-administration of estradiol benzoate had no antagonistic effect upon the antitumor responses produced by LY117018. The mechanism of action of LY117018 is not known. The failure of estradiol benzoate to affect PAIII growth and metastasis supports the contention that the responses to LY117018 are not attributable to simple antagonism of estrogen action. LY117018 may be exerting its antitumor effects through autocrine, paracrine, or endocrine mechanisms. LY117018 represents a class of agents with potential utility in treating metastatic cancer of the prostate.
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PMID:Comparative antitumor effects of hormonal ablation, estrogen agonist, estrogen cytotoxic derivative, and antiestrogen in the PAIII rat prostatic adenocarcinoma. 151 32

We have studied the estradiol sensitivity of primary human breast carcinomas in organ culture in a prospective pilot series of 109 tumors. The effect on plasminogen activator (PA) production was used as the end-point of estrogen action. We found that: (i) All tumors secreted detectable levels of urokinase-type PA (uPA); the level of basal uPA production was markedly heterogeneous but showed a weak association with the level of estrogen receptor positivity (p = 0.049). (ii) Only 23.5% of the tumors secreted tissue-type PA (tPA) in addition to uPA; a higher proportion of these tumors had histological characteristics indicative of good prognosis (18% vs. 3% of tumors secreting only uPA). (iii) Estradiol modulated uPA production and this effect was receptor-mediated. (iv) Responsiveness to estradiol was limited to a subset (25 of 60 or 41.7%) of estrogen and progesterone-receptor-positive tumors. (v) Of 20 evaluable patients with lymph-node and receptor-positive breast cancer who received adjuvant anti-estrogen therapy, 11 were identified as estradiol-sensitive by the in vitro PA assay; of these, 10 had no evidence of disease after a median follow-up period of 3+ years. In contrast, of 9 patients with tumors identified as estradiol-insensitive, 4 developed metastases within 3+ years of follow-up. (vi) Consistent with the previously reported inhibitory effect of corticosteroids on uPA production in organ cultures of human tumors, the basal culture level of uPA produced by tumors from patients receiving corticosteroids at the time of surgery was significantly lower than the level of uPA in the remaining tumors (p = 0.029). Also, tumors from patients receiving thyroid hormone, known to stimulate uPA in vitro, showed a slight trend toward increased production of uPA. These results show that hormone effects on tumor PA production are qualitatively similar in organ culture and in the host. This and the emerging individual correlation between sensitivity to estradiol in vitro, as determined by PA, and the clinical effectiveness of anti-estrogen therapy, underscore the potential usefulness of the organ culture approach.
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PMID:Estradiol modulation of plasminogen activator production in organ cultures of human breast carcinomas: correlation with clinical outcome of anti-estrogen therapy. 190 Dec 98

A high incidence (27.5%; 174 of 633) of spontaneous, malignant ovarian granulosa cell tumors develop in (SWR x SWXJ-9)F1 hybrid females between 3 and 6 weeks. Granulosa cell tumors developed in predictable stages, starting as preneoplastic lesions appearing as hyperemic follicles on the ovarian surface. These follicles were characterized by hypertrophied theca, degenerating oocytes, and large fluid- or erythrocyte-filled antra lined by irregular masses of granulosa cells. Rapidly proliferating granulosa cells filled the antra and the theca/interstitial cells became more dysplastic as granulosa cell tumors developed. Thus the morphology of the preneoplastic lesion suggests that disturbed mechanisms for normal follicular development underlie granulosa cell tumor initiation. Estradiol treatment before but not after preneoplastic lesions appeared inhibited granulosa cell tumor formation. By 6 to 9 months 42% of these mice show metastases in major abdominal and thoracic organs. Thus this model can be experimentally analyzed both for mechanisms of granulosa cell tumor initiation and subsequent malignant progression.
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PMID:Ovarian granulosa cell tumorigenesis in SWR-derived F1 hybrid mice: preneoplastic follicular abnormality and malignant disease progression. 238 55

Application of aromatase inhibitors to the treatment of conditions in which estrogen plays, a role is discussed. Studies in vitro demonstrate that 4-hydroxyandrostenedione (4-OHA) is a potent inhibitor of aromatase. The compound reduces ovariant estrogen production and causes regression of carcinogen (DMBA)-induced mammary tumors in the rat. In the rhesus monkey, 4-OHA was also shown to inhibit peripheral aromatization. To date 58 postmenopausal breast cancer patients with advanced metastatic disease have received 500 mg im weekly while 31 patients received 250 mg 4-OHA orally per day. Estradiol levels were significantly reduced in all patients from a mean of 7.2 + 0.8 pg/ml to 2.8 + 0.3 pg/ml. Of patients receiving 4-OHA im 27% had partial or complete responses and in 10% of patients the disease was stabilized. Similar responses occurred in the patients receiving 4-OHA orally. These results suggest that 4-OHA is effective and that this compound and other aromatase inhibitors could be valuable new additions to the treatment of breast cancer.
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PMID:Aromatase inhibitors: basic and clinical studies. 332 May 68

This article presents the case of a 30-year-old woman who developed halo cutaneous melanoma. She had been taking oral contraceptives (Norinyl) for about 5 years before diagnosis. Following wide excision of the melanoma, the patient remained clinically free of tumor for 5 years. However, in a subsequent pregnancy, she developed metastases to the liver that became evident in the immediate postpartum period. Long-term survival associated with cutaneous hypopigmentation has been reported and occurred in this patient. There is considerable debate as to whether oral contraceptives or pregnancy can influence the occurrence and course of melanoma. Also unclear is whether oral contraceptive use or a subsequent pregnancy in women with a history of melanoma will accelerate the growth of latent metastases, stimulate a benign pigmented lesion to become malignant, or cause a previously removed melanoma to recur and metastasize. Given the lack of uncertainty in this area, it is recommended that women with a history of melanoma use a nonhormonal method of contraception. Frequent follow up and thorough physical examinations during pregnancy are essential, and any suspicious skin lesions should be biopsied early. To better answer the questions raised by cases such as this, establishment of an organized mechanism for the registry of patients with melanoma who subsequently become pregnant is suggested. A cooperative prospective melanoma study could accumulate the necessary data on tumor site and thickness, staging, parity, and the use of hormonal contraception.
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PMID:Pregnancy and hormonal influences on malignant melanoma. 381 62

Clinical, serological and lymphocyte studies were done on 435 patients with biopsy proved anaplastic nasopharyngeal carcinoma (NPC) in various clinical status, at the National Taiwan University Hospital, from January 1980 through June 1983. Studies on 134 normal control were also done. Using immunofluorescent antibody method, seropsitive rates of the antibody titers against viral capsid antigens (VCA) and early antigens (EA) of Epstein-Barr (EB) virus were 70.8%-100% for anti-VCA/IgG titers (greater than or equal to 1:640), 81.0%-100% for anti-VCA/IgA titers (greater than or equal to 1:40), 66.7%-93.8% for anti-EA/IgG titers (greater than or equal to 1:160), and 40.0%-87.5% for anti-EA/IgA titers (greater than or equal to 1:40) in NPC patients with disease. They decreased to 10.5%-21.7% in remission patients. In contrast, they were less than 5% in the control. Mean total serum IgG and IgA levels were moderately increased to around 1,500 mg/dl and 300 mg/dl respectively, in all patients. The increase was most remarkable in patients with liver metastases. In control the values were 1,211 mg/dl and 223 mg/dl, respectively. Mean serum IgM, C3 and C4 amounts of NPC patients were not significantly different from those of the normal control, the latter were 129, 80.3 and 43.2 mg/dl, respectively. Serum acid phosphatase and calcium levels of NPC patients were all in the normal range of 0.1-2.0 BU/ml and 2.0-3.0 mmol/dl, respectively. Serum GOT, GPT, alkaline phosphatase, lactate dehydrogenase and mucoprotein were elevated either alone or in combination in some patients before treatment, in many patients with neck recurrence or distant metastases, but in all patients with liver metastases. Using monoclonal antibodies (Ortho Inc., U.S.A.) to define lymphocyte subsets, B lymphocytes comprised about 12% and T lymphocytes about 60% in the patients, whereas they were 11.9% and 73.1% in the control. The helper/suppressor ratio was 1.7 in the control and about 1.0 in NPC patients, and was only 0.8 in remission patients. The lack of correlation between the seropositive rates of anti-VCA antibodies and the helper/suppressor ratio might indicate different manifestations of humoral and cellular immunity in patients with NPC.
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PMID:Humoral and cellular immunity in patients with nasopharyngeal carcinoma. 608 49

A 21-year-old woman presented with a 12-month history of epigastric pain, and for 3 months she had noticed a mass in the right hypochondrium. She had taken 'Norinyl-1' (norethisterone 1 mg and mestranol 50 mcg) for 5 years. She smoked 20 cigarettes a day but drank little alcohol. Physical examination revealed irregular hard hepatomegaly 10 cm below the right costal margin. Hepatitis B surface antigen was not detected in the serum and alpha fetoprotein levels were normal ( 10 M.R.C. units). A liver scan showed a large space-occupying lesion in the right lobe of the liver, and liver biopsy revealed a cholangicarcinoma with striking fibrous reaction. Multiple shadows consistent with metastases were present on chest X-ray, but no bony deposits were found on radiological skeletal survey or bone scan. The serum calcium was persistently high (2.74-2.92 mmol/l) but fell on prednisolone therapy. Serum parathyroid hormone levels were normal. A causal relation between oral contraceptives and hepatic adenoma is now generally accepted, and several patients with hepatocellular carcinoma have also been reported. We have been able to find only 1 previous report of cholangiocarcinoma in a young female taking oral contraceptives, and there is 1 report of this tumor in a man taking high doses of anabolic steroids for refractory anemia. This tumor has its peak incidence in the 6th decade and is very rare in the 3rd decade. The association with hypercalcemia due to pseudohyperparathyroidism is well recognized. In only some cases are parathyroid hormone levels raised, and the cause of the pseudohypercalcemia in our patient is unknown.
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PMID:Cholangiocarcinoma and oral contraceptives. 610 61


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