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)

It has been proposed that early treatment of patients with advanced prostatic cancer by surgical or medical orchiectomy when combined with a direct acting antiandrogen will result in a more complete form of androgen blockade, thereby increasing response and survival rates compared to orchiectomy alone. We treated 55 patients with previously untreated advanced prostatic cancer by bilateral orchiectomy and additional administration of 50 mg. of the direct acting antiandrogen cyproterone acetate orally per day. Therefore, these patients have undergone a combination therapy that meets the requirements of the proposed complete androgen blockade. All 22 patients with metastases at hospitalization died during the first 4 years of treatment. Among the 33 patients without clinical evidence of metastases at hospitalization 18 were alive after 5 years. Retrospectively, the direct observed 5-year survival rate for the patients treated with a complete androgen blockade did not show any advantage compared to reported data with orchiectomy alone.
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PMID:Inability of complete androgen blockade to increase survival of patients with advanced prostatic cancer as compared to standard hormonal therapy. 295 9

Because of its rare occurrence in the human, the endocrinologic and receptor-related aspects of an uterine leiomyosarcoma (LMS) are poorly understood when compared to what is known of, say, human endometrial cancer. Thus, to increase our understanding, we have succeeded, by the string method, in inducing an uterine LMS in the mouse and have studied the possibility of hormonal therapy as a method of treatment. The findings of our study are enumerated as follows: 1. The induced uterine LMS had an estrogen receptor, which was confirmed by a biochemical assay and, morphologically, by a PAP (the peroxidase anti-peroxidase technique); 2. The growth of this tumor was significantly inhibited by MPA (medroxyprogesterone acetate) therapy (100 mg/kg); 3. After MPA therapy, the estrogen receptor levels were increased, especially in the nucleus; and, 4. The growth of a secondary tumor, transplanted after the initial hormone therapy, was not inhibited by the readministration of MPA. Our results suggest that this experimentally-induced uterine LMS in the mouse provides a useful means to study therapeutic treatment, and may assist in furthering our understanding of human uterine LMS and lead to finding an effective therapy.
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PMID:[Experimental study of the treatment of uterine leiomyosarcoma in the mouse with progestogen]. 297 92

Thirty patients with hormone-resistant metastatic progressive prostatic carcinoma were treated with sequentially alternating hormone chemotherapy. They were given 1,000 mg medroxyprogesterone acetate (MPA) orally for 26 days followed by intravenous doses of 25 mg/m2 epirubicin weekly for 4 weeks. The median duration of the treatment was 29 weeks (range 8-84). In 2 patients a more than 50% reduction in the size of measurable lymph node metastases was observed and in 2 others skeletal metastases decreased. Serum acid phosphatase normalized in 6 patients. Twenty-five patients achieved a subjective response (median duration 24 weeks; range 4-76 weeks). Median survival from the start of treatment (30 +/- 16 weeks) was unrelated to the achievement of subjective response. Normalization of serum acid phosphatase and a more than 50% reduction in serum alkaline phosphatase correlated with the achievement of a subjective response. Toxicity was generally mild, but in 1 case therapy was discontinued because of suspected cardiotoxicity. Sequentially alternating high-dose MPA low-dose epirubicin hormone chemotherapy has a marginal objective effect but a good subjective effect on progressing hormone-resistant prostatic cancer.
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PMID:Sequentially alternating hormone chemotherapy with high-dose medroxy-progesterone acetate and low-dose epirubicin for the treatment of hormone-resistant metastatic prostatic cancer. 297 21

To study the production and significance of prostacyclin (PGI2) and thromboxane A2 (TxA2) in breast cancer, tissue fragments of breast cancer (n=23) and mastopathy (n=10) were superfused in vitro and the release of 6-keto-PGF1 alpha (a metabolite of PG12) and TxB2 (a metabolite of TxA2) measured by radioimmunoassay. Breast cancer formed more 6-keto-PGF1 alpha (4.5 +/- 0.9 ng min-1 g-1 of tissue dry weight, mean +/- s.e.) and TxB2 (2.5 +/- 0.6 ng min-1 g-1) (P less than 0.01) than did mastopathic breast (1.4 +/- 0.5 and 0.4 +/- 0.1 ng min-1 g-1, respectively). These productions were similar in steroid receptor positive and negative tumours. Breast cancer metastasized in 15 patients during the follow-up time of 3.7 +/- 0.7 years, but the initial prostanoid productions in these patients were not different from those in nonmetastatic patients. Two patients died from metastases, but their initial mammary production of prostanoids was not profoundly different from those in the survivors. In 8 patients (4 with steroid receptor positive and 4 with negative tumour), the cancer tissue was superfused in the presence or absence of medroxyprogesterone acetate (100-5000 ng ml-1), which is commonly used for treatment of breast cancer. This hormone had no effect on mammary PGI2 and TxA2 production. We thus conclude that the PGI2 and TxA2 productions are increased in mammary cancer but that this may not be of primary significance for metastastic spread.
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PMID:Prostacyclin and thromboxane in breast cancer: relationship between steroid receptor status and medroxyprogesterone acetate. 298 66

We have shown previously that an increase in tumor invasion and metastases occurred concurrently with a decrease in collagen content of the extracellular matrix surrounding the C3H mouse mammary adenocarcinoma borne by C3H/HeJ mice. In this paper we report the production of collagenase and elastase activities by the primary tumor cultures and three types of cloned C3H mouse mammary adenocarcinoma cell cultures. The primary tumor cell cultures and tumor-associated stromal cultures produced large amounts of collagenase and elastase activities. On the other hand, the primary tumor capsule cultures produced little or no collagenase and elastase activities even though they produced type I collagen. The production of proteases by the primary tumor cultures decreased along with time and with an alteration in the morphology of cell populations and/or passage of the cultures. The three clones of tumor cell cultures produced variable amounts of collagenase in response to induction by phorbol myristate acetate, an agent that stimulates maximal collagenase production. In contrast, all three cloned cultures elaborated significant amounts of elastase that degraded insoluble ligamental elastin, and most of the elastase production was increased further in response to induction by phorbol myristate acetate. Each cloned cell population exhibited differences in their production of collagenase and elastase in parallel with their difference in growth kinetics, yet these cells still possess the distinctive properties of the tumor. However, a unit amount of collagenase produced by each of the cloned cultures, with or without induction by phorbol myristate acetate, was less than that of the primary tumor cultures. Results suggest that some cell types or combination of cell types in the heterogeneous cell population of the tumor and/or their products appear to be responsible for the increased production of collagenase and elastase activities and for the invasiveness of a malignant tumor.
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PMID:Collagenase and elastase production by mouse mammary adenocarcinoma primary cultures and cloned cells. 302 19

Progestational agents, such as megestrol acetate and medroxyprogesterone acetate, are effective hormonal treatments for metastatic breast cancer in postmenopausal women. Clinical trials of these agents have demonstrated that 30% to 60% of patients will experience objective tumor response, depending on pretreatment prognostic variables. Although optimal doses and schedules have not been fully defined, current studies are investigating the therapeutic effectiveness of high-dose progestins. Toxicity of these drugs is mild and generally limited to weight gain related to their anabolic activity. Progestins are active second-line agents for metastatic breast cancer in postmenopausal women. In selected patients, they appear to be equivalent to tamoxifen as first-line therapy for metastatic disease. As more patients are exposed to prolonged adjuvant tamoxifen therapy, the role of progestins as first-line hormonal therapy at the time of relapse is likely to expand.
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PMID:Progestational agents in advanced breast cancer: an overview. 302 51

We have adopted various approaches to identifying the genes(s) involved in metastasis. The first has been to observe whether introducing a defined activated oncogene (c-Ha-ras 1) into non-neoplastic cells confers not only tumorigenicity but other characteristics of malignancy. A second approach involves transfection of total genomic DNA from highly metastatic into nonmetastatic tumour cells. Thirdly, we are studying whether treatment of weakly metastatic tumour cells with agents known to influence tumour progression and gene expression (e.g. 12-O-tetradecanoylphorbol-13-acetate or 2'-deoxy-5-azacytidine) can affect metastatic capability. It was found that 3T3 fibroblasts which incorporated and expressed the activated rasH oncogene became tumorigenic and capable of lung colonization but not spontaneously metastatic. Additionally, transfection of inert tumour cells with DNA from highly metastatic human and animal cell lines sometimes markedly augmented their spontaneous metastatic capability and their lung colony-forming potential and induced them to form deposits in many extrapulmonary sites. Treatment of some tumour cell lines with azacytidine and 12-O-tetradecanoylphorbol-13-acetate markedly increased their metastatic behaviour after subcutaneous inoculation. Because several cell divisions occurred to produce the subcutaneous tumour before the cells disseminated, we consider the changed phenotype to be heritable and probably caused by alterations in gene expression. These results suggest that components of the metastatic phenotype are heritable and highly conserved in evolution and can be conferred on previously non-metastatic tumour cells by transfer of genomic DNA. In other studies we found that metastasizing tumour cells reach all organs in the body within minutes of entry into the blood but that the distribution of subsequent secondary tumours is neither uniform nor proportional to the numbers of cells retained in each site. The patterns of distribution of metastases tend to be related to the tissue of origin of the primary tumour. This was confirmed in observations on patients with intractable malignant ascites treated with peritoneo-venous shunts. Co-culture of tumour cells with fragments of various organs in vitro supported the conclusion that the normal cells of organs can support or inhibit secondary tumour formation. These observations collectively indicate that metastasis results from acquired abnormalities in gene regulation in tumour cells, but that the resulting abnormal cell behaviour can sometimes be modified or inhibited by local or systemic conditions in the host.
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PMID:Molecular genetics of metastasis. 307 33

Nocardia delipidated cell mitogen (NDCM), a particulate fraction prepared from Nocardia opaca, injected i.p. in an oil/water emulsion to F6 rhabdomyosarcoma-bearing rats, inhibited the development of pulmonary metastases; 6 out of 10 rats were protected. Repeated i.p. administration of emulsified NDCM and of two other compounds, a Nocardia water soluble mitogen (NWSM a hydrosoluble fraction) and purified cell walls (CW, an insoluble macromolecular fraction) in Lewis lung carcinoma (LLC)-bearing mice resulted in a significant reduction of lung metastases. The efficiency of these fractions was enhanced by association with monokines. A combination regimen of NDCM, NWSM, and CW (100 micrograms/0.1 ml) and monokines (0.1 ml), injected i.p. in LLC-bearing mice, yielded a greater antimetastatic effect than either therapy alone. Peritoneal macrophages from mice which had been injected i.p. with NWSM or CW, when triggered either by TPA (tetradecanoyl phorbol acetate) or by zymosan, released large quantities of hydrogen peroxide and had a high rate of glucose consumption. These macrophages were activated as judged by their cytostatic activity against syngeneic P815 mastocytoma growth; they expressed biochemical markers which have been reported to characterize the activated state. Incubation of thioglycollate-elicited peritoneal macrophages with NWSM, and monokines for 72 h resulted in a cytotoxic activity against labeled LLC cells; addition of macrophage activating factor significantly increased the cytotoxic capacity of these macrophages. In view of this we postulate that the antimetastatic effect of soluble and insoluble N. opaca fractions and monokines might be mediated by activated peritoneal macrophages.
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PMID:Antimetastatic effect of immunomodulators from Nocardia opaca in mice and rats activation of peritoneal macrophages by these fractions. 311 66

Administration of medroxyprogesterone acetate IP in advanced cancer with peritoneal metastases and ascitic effusion generates considerably higher drug plasma levels than those observed after PO or IM treatment. Comparison of areas under the time-concentration curves (AUC) with reference to the three administration routes indicates that after oral administration only 0.2%-17.4% (mean 5.7%; SD 3.77; 40 patients) of the administered dose is absorbed; after IM treatment a daily absorption of 0.7%-7.7% (mean 2.5%; SD 1.66; 30 patients) of the administered dose per injection site was computed.
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PMID:Medroxyprogesterone acetate bioavailability after high-dose intraperitoneal administration in advanced cancer. 315 49

Surgery can play an important role in selected patients with metastatic renal cell carcinoma although nephrectomy alone neither promotes regression of metastases nor improves survival. However, nephrectomy preceded by renal infarction and followed by medroxyprogesterone acetate produced ten complete responses, nine partial responses, and 22 stabilizations among 145 patients (CR + PR = 13%; overall response rate = 28%). Only patients with parenchymal pulmonary metastases without adenopathy, pleural effusion, or other organ involvement responded consistently (23% objective, 41% overall), and we currently recommend this combination therapy only for this group. However, infarction alone is an easy way to palliate symptoms due to primary or secondary tumors.
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PMID:Surgery of metastatic renal cell carcinoma and use of renal infarction. 329 53


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