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)

In 1941, Huggins and his colleagues discovered that testicular androgens exert a stimulatory effect on prostate cancer growth. Our group has made the key observations that the human adrenals, in addition to the tests, also secrete important amounts of androgens and cancer cells exhibit a marked heterogeneity of androgen sensitivity. In fact, human adrenals secrete large amounts of precursor steroids that are converted into active androgens in peripheral tissues (including the prostate), thus providing 40% to 50% of total androgens in adult men. The action of these androgens remaining after castration can be inhibited in prostatic cancer tissue by administering a pure antiandrogen that also decreases the local concentration of dihydrotestosterone (DHT). The castration levels of serum testosterone left in men after castration have an important stimulatory activity on the growth of androgen-sensitive normal as well as cancer tissues. Cancer cells have markedly different requirements for androgens. Some cell clones can grow in the presence of minimal amounts of androgens, requiring more complete androgen blockade and more potent antiandrogens for inhibiting growth. Among the compounds recommended as antiandrogens, the most unexpected finding is that many of them are devoid of any antiandrogenic activity. In fact, medroxyprogesterone acetate, chlormadinone acetate, and megestrol acetate have androgenic activity, but do not inhibit the peripheral action of DHT in prostatic tissue. These compounds should not be classified as antiandrogens. Cyproterone acetate, on the other hand, is a mixed agonist-antagonist. The only compounds showing pure antiandrogenic activity are Flutamide and its analogues. There is thus a need for a more complete blockade of androgens of both testicular and adrenal origins in order to exert a maximal inhibitory effect on cancer growth. We have therefore performed clinical studies in previously untreated stage D2 and C prostate cancer patients with the combination therapy using the LHRH agonist [D-Trp6, des Gly NH2(10)] LHRH ethylamide and the antiandrogen Flutamide. There was a significant increase in patients with a complete response, as compared with studies limited to the removal or blockade of testicular androgens. There was also a significant decrease in the number of non-responders, an increased duration of positive response, and a decrease in the death rate. This was achieved with minimal or no side effects, thus preserving a good quality of life.
Cancer Metastasis Rev 1987
PMID:Combination therapy in stage C and D prostatic cancer: rationale and five year clinical experience. 332 35

A strong correlation was found between the basal levels of membrane-bound protein kinase C and the ability of B16 melanoma cell sublines (F10, F1, and BL6) to metastasize to the lung after intravenous injection. By treating with tumor-promoting phorbol esters for 1 hr, the low-metastasizing F1 cells exhibited both translocation of protein kinase C from cytosol to plasma membrane and an increase in metastasis to a level comparable to the (untreated) highly metastatic subline F10. Prolonged treatment of melanoma sublines with phorbol 12-myristate 13-acetate for 24 hr resulted in both inactivation of protein kinase C activity and loss of their metastasizing capabilities. Under conditions that induced only the activation of protein kinase C but not its membrane association, no increase in metastasis occurred, suggesting that activation of protein kinase C alone is insufficient to promote metastasis and that its membrane association is also necessary. Exposure of B16 melanoma sublines to phorbol esters for 1 hr had (i) no effect on the growth and morphology of these cells in vivo and in vitro and (ii) a short-term effect (approximately equal to 5 hr) on membrane association of protein kinase C. Nonetheless, in this period, the membrane-bound protein kinase C, probably by influencing cell-surface and cell-attachment properties, increased the retention of circulating melanoma cells in the lung, which eventually led to an increased number of metastatic nodules. The membrane-bound protein kinase C activity also correlated with metastatic ability in rapidly growing cells, growth-arrested cells, and cells growing in a low-Ca2+ medium. The results strongly suggest that the membrane-bound protein kinase C influences hematogenous metastasis of tumor cells and show that tumor promoters like phorbol esters have an additional role in promoting hematogenous spread of cancer in the body.
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PMID:Tumor promoter-induced membrane-bound protein kinase C regulates hematogenous metastasis. 342 45

A series of 70 patients with the squamous cell carcinoma of the lip and followed-up for at least 5 years, was assessed on light microscopy and using histochemical staining for ANAE (acid-naphthyl acetate esterase) to demonstrate the morphological manifestations of tumor-host reactivity. The factors analysed include cancer differentiation (intrinsic malignancy) and stromal reactions (intensity of the immunocompetent cell infiltrate including the mast cells and the subpopulations, i.e. B- or T lymphocytes or mononuclear phagocytes). Differentiation of the lip cancer was shown to be directly (although not statistically significantly) related to the 5-year survival, as was also the intensity of the stromal immunocompetent cell infiltration. Cancer metastases were evidently the most powerful prognostic determinants, their development being influenced both by the intensity of the stromal immunocompetent cell infiltrate and cancer differentiation. B lymphocytes far outnumbered the T and MPS cells in all the infiltrates studied, the percentages of the latter two cell types, however, being inversely related to the intensity of the infiltrate. The cell composition in the infiltrates was seemingly without effect on the frequency of metastases and the 5-year survival, as was the stromal mast cell reaction, too. It was concluded that analysis of tumor-host relationships using a variety of morphological and immunohistochemical techniques may be of benefit in predicting the clinical course of lip cancer.
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PMID:Tumor differentiation and tumor-host interactions as prognostic determinants in squamous cell carcinoma of the lip. 351 41

Adoptive immunotherapy with lymphokine-activated killer cells and recombinant interleukin 2 (IL 2) can produce significant reduction of visceral metastases in tumor-bearing mice and, as shown recently, in humans with disseminated cancer. Because further dose escalations of IL 2 have been prevented by the development of a vascular leak syndrome (VLS) in both mice and humans, we investigated this VLS in mice undergoing the systemic administration of high-dose IL 2. A model for quantitating capillary permeability was used in which 125I-bovine serum albumin was injected i.v., and 2 hr later, tissues were counted in a gamma analyzer. A permeability index (PI) was calculated by dividing the mean counts per minute (cpm) of tissues from IL 2-treated mice by those from control animals. The injection of IL 2 produced increases in vascular permeability that were most pronounced in the thymus, spleen, lungs, liver, and kidneys (PI = 18.0, 10.0, 9.7, 6.7, and 6.3, respectively, on day 6). The development of the VLS was highly dependent on the number of days of IL 2 treatment (for example, the lungs contained 638, 1382, 3350, and 6187 cpm after 0, 1, 3, and 6 days of IL 2, respectively). Moreover, the degree of the VLS was directly related to the dose of IL 2 administered. Measurement of the wet and dry weights of lungs from IL 2-treated mice demonstrated that IL 2 produced a dramatic increase in their water weight (from 0.10 g at base line to 0.22 g after 200,000 U of IL 2 for 6 days). The injection of the IL 2 excipient failed to induce capillary leakage in tissues. Immunosuppression of mice by pretreatment irradiation (500 rad) or by injection of cyclophosphamide or by concurrent use of cortisone acetate markedly reduced or eliminated the development of the VLS. Similarly, the VLS was not observed in nude mice receiving IL 2. Thus, the administration of IL 2 produces a dose-limiting VLS that may be mediated, directly or indirectly, by host lymphoid elements.
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PMID:Extravasation of intravascular fluid mediated by the systemic administration of recombinant interleukin 2. 352 89

Combined therapy was used on a consecutive series of 48 patients with extrapelvic Ewing's sarcoma at the Rizzoli Orthopaedic Institute. The adjuvant chemotherapy protocol (VCR, ADM, D-ACT, EDX) was identical in all patients whereas local treatment consisted of amputation, resection and radiation treatment or radiation alone. At a mean follow-up of 58 months (39-78) 30 patients (60%) were free of the disease. This is a significantly higher percentage than that obtained in the same period with adjuvant chemotherapy using only 3 drugs (VCR, ADM, EDX). As far as the type of local treatment is concerned, the percentage of local recurrences and metastases was lower when the primary lesion was treated with surgery or surgery combined with radiotherapy, rather than radiation treatment alone. These suggest that if associated with radiation treatment and chemotherapy, surgery can play an important role that should be considered in the treatment of extrapelvic Ewing's sarcoma.
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PMID:[Therapy of non-metastatic Ewing's sarcoma (pelvis excluded). Results obtained in 48 cases combining local therapy (radiation and/or surgical) and adjuvant chemotherapy with vincristine, adriamycin, dactinomycin and cyclophosphamide]. 357 34

The effect of endocrine therapy in 465 postmenopausal patients with advanced breast cancer who entered four consecutive, randomized trials has been related to the site of the metastases. Patients received either tamoxifen (T) alone or T in combination with medroxyprogesterone acetate, diethylstilbestrol, halotestin, or aminoglutethimide. The overall response rate was 40%. Responses were most frequently seen in patients with metastases in soft tissue, and the duration of response to endocrine therapy in these patients was longer than for those with metastases in bone or viscera (p less than 0.00001). In addition, the response rate was inversely correlated with the number of main metastatic sites in patients with soft tissue metastases, whereas the response rate was not associated with the number of metastatic sites in patients with metastases in bone and viscera. Survival after first recurrence was significantly longer in responding patients with soft tissue lesions compared to those with recurrence in bone or viscera. In contrast, survival after first recurrence was identical in patients with nonresponding disease, irrespective of dominant site of metastases. The outcome of endocrine therapy depends partially upon the dominant site of metastases. This may reflect a difference in biological characteristics of human breast cancer tumor cells that metastasize to different sites.
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PMID:Metastatic pattern and response to endocrine therapy in human breast cancer. 359 85

Forty-three males with recurrent and metastatic cancer of the prostate were treated with megestrol acetate (160 mg/day orally) after having failed first-line hormonal treatment (orchiectomy or diethylstilboestrol). Thirty-seven patients were evaluated objectively for response, 28 of whom received the drug for more than 6 weeks. One patient had a partial response (National Prostatic Cancer Project criteria) and seven had stable disease. Toxicity was usually mild, although five patients developed a transient rise in liver enzymes and one patient had a grand mal fit. Three patients showed evidence of tumour "flare". Megestrol acetate has only limited efficacy in patients previously treated for prostatic cancer by hormonal manipulation.
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PMID:Phase II study of megestrol acetate for metastatic carcinoma of the prostate. 359 1

An intimate interplay between the host factors and the tumour seems to be operative in lip cancer, and is undoubtedly capable of modifying the clinical course of the disease. A series of 70 patients with squamous cell carcinoma of the lip was assessed by light microscopy and using histochemical staining for acid alpha-naphthyl acetate esterase to demonstrate the morphological manifestations of tumour-host reactivity. The factors analysed include stromal reactions; intensity of the immunocompetent cell infiltrate including mast cells, and the subpopulations, i.e. B or T lymphocytes and mononuclear phagocytes (MPS cells). B lymphocytes far outnumbered the T and MPS cells in all the infiltrates studied, the percentages of the latter two cell types being inversely related to the intensity of the infiltrate, however. The cell composition in the infiltrates lacked statistically demonstrable effect on the frequency of metastases and the 5-year survival, as did the stromal mast cell reaction, too.
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PMID:Immunocompetent cell reaction in prognostic evaluation of squamous cell carcinoma of the lip. 361 94

Malignant cells within solid tumors commonly exhibit phenotypic changes such as alterations in karyotype and acquisition of the ability to invade and to metastasize. We have used a fibrosarcoma, grown subcutaneously in C57BL/6 mice, to study the mechanisms underlying this phenotypic instability. Tumor-bearing animals were injected with phorbol myristate acetate (PMA) and then the tumors were transplanted to animals without further PMA treatment. These tumor cells were tum+, that is, unlike the parental tumors, they were able to grow in animals immunized against the parental tumors. This property was maintained for at least 6 tumor passages after the initial PMA injections. Thus, PMA appears to be able to induce an unstable tum+ phenotype in these cells at relatively high frequency.
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PMID:In vivo induction of tumor variants by phorbol 12-myristate 13-acetate. 369 May 9

The progression of papillomas to squamous cell carcinomas (malignant conversion) was studied in the skin of SENCAR and Charles River CD-1 mice, using a three-stage treatment protocol. After initiation with 7,12-dimethylbenz(a)anthracene (DMBA) (stage 1) and limited promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) (stage II), papilloma-bearing mice were treated (stage III) with either tumor initiators, such as urethane, N-methyl-N'nitro-N-nitrosoguanidine (MNNG) or 4-nitroquinoline-n-oxide (R-NQO), the promoter TPA, or solvent (acetone). Similar final carcinoma yields were found in the mice treated in stage III with TPA or acetone, although carcinomas developed earlier in the TPA-treated mice. In contrast, treatment with tumor initiators in stage III increased both the rate of appearance and the final yield of carcinomas. Similar results were obtained in both SENCAR and CD-1 mice. A papilloma stage appears to be necessary for carcinoma development since elimination of TPA treatment in stage II greatly reduced the incidence of both papillomas and carcinomas in both stocks of mice. The heterogeneity of papillomas with regard to progression to carcinomas is demonstrated by the low rate of conversion of TPA-dependent papillomas and the high rate of conversion of persistent papillomas in CD-1 mice. The carcinomas that develop using the three-stage regimen vary in metastatic potential. In CD-1 mice, the frequency of metastases to lymph nodes were similar in groups treated in stage III with MNNG, urethane, 4-NQO, TPA, or acetone, but treatment with urethane substantially increased metastases to the lung.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Malignant conversion and metastasis of mouse skin tumors: a comparison of SENCAR and CD-1 mice. 378 Jun 34


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