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 effects of Corynebacterium parvum (C. parvum) on Lewis lung tumour metastases have been studied. I.v. and i.p., but not s.c. C. parvum significantly reduced pulmonary metastases. When combined with excision of the primary tumour, C. parvum given not more than 2 days before caused slight reduction of metastases, but when given earlier, it caused significant reduction and some mice were cured. Metastases were increased by silica or cortisone acetate but were unaffected by trypan blue. The antimetastatic action of C. parvum was not altered by these treatments. Thymectomy and irradiation did not affect tumour metastases, or the antimetastatic action of C. parvum, whereas ALS depressed metastasis and abrogated the protective effects of C. parvum. It appears that the inhibitory effects of C. parvum on tumour metastases are mediated through macrophages in concert with a subpopulation of T2 lymphocytes.
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PMID:Effects and mode of action of Corynebacterium parvum on murine tumour metastases. 60 10

The case is reported of a patient with pulmonary metastases from a renal adenocarcinoma who experienced subjective improvement and objective tumor regression on Bacillus Calmette-Guerin (BCG) and megestrol acetate therapy. In a subsequent Phase II trial, no objective responses were noted among 15 patients treated with megestrol acetate (160 mg/day X 56 days) and BCG (five immunizing doses intradermally, every 2 weeks X 5). It is concluded that this treatment regimen is not clinically useful in patients with metastatic renal adenocarcinoma.
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PMID:The phase II evaluation of Bacillus Calmette-Guerin plus megestrol acetate in patients with metastatic renal adenocarcinoma. 61 10

The effects of operation (lower-limb amputation) on the growth of the Lewis lung tumour and its metastases were studied. The role of C. parvum in counteracting these effects was investigated. Anaesthesia alone or with amputation did not affect primary tumour growth. C. parvum depressed this growth. Anaesthesia did not affect the number of pulmonary metastases, but amputation caused a significant increase. C. parvum inhibited metastases and completely counteracted the effects of operation on them. Large doses of cortisone acetate significantly increased metastases but small doses had no effect. Experiments with adrenalectomized mice suggested the effects of operation were due to non-specific stress.
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PMID:Effects of amputation and Corynebacterium parvum on tumour metastases in mice. 64 27

The effects of Corynebacterium parvum and cortisone acetate (CA) on the primary Lewis lung carcinoma and its pulmonary metastases were investigated. C. parvum given IV either on the same day or 7 days after tumour inoculation, reduced primary tumour growth, while 2.5 mg CA (high-dose) given SC 4 and 11 days after tumour, alone or in combination with C. parvum, administered on day 0, reduced primary tumour growth to the same extent as C. pravum alone. High-dose CA given on days 2 and 6 had no effect on primary tumour growth or the action of C. parvum, administered on day 7, while 0.05 mg CA (low-dose) given on days 4 and 11 did not alter tumour growth or the action of C. parvum given at the same time as tumour. High-dose CA given 4 and 11 days after tumour caused a significant enhancement in metastases. C. parvum given to these mice on the same day as tumour significantly reduced the pulmonary nodules but only to the level found in control, saline-treated mice. In mice given C. parvum alone, metastases were significantly reduced when compared with controls. Similarly, high-dose CA given on days 2 and 6 significantly enhanced metastases, and C. parvum on day 7 reduced their level to that found in control mice. Low-dose CA had no effect on the number of metastases or the antimetastatic action of C. parvum. The relevance of these results to the clinical situation is discussed.
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PMID:Effects of Corynebacterium parvum and cortisone on the primary Lewis tumour and its metastases. 66 56

Buffalo strain male and female rats were given methylazoxymethanol acetate (20% solution) intraperitoneally 20 mg/kg body weight weekly for 9 weeks, and killed 27 weeks later. Carcinomas of the large intestine, predominantly in the descending colon, developed in some of the rats. The incidence was higher in male than in female rats. Polypoid carcinomas were observed more often in male rats and sessile carcinomas with metastases in the female rats. Carcinomas were not observed in organs other than the large intestine.
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PMID:Carcinomas of the colon in Buffalo strain rats given intraperitoneal injections of methylazoxymethanol acetate. 96 70

Most women with "early" breast cancer have distant metastases by the time the primary growth comes to diagnosis. This observation is based upon the fact that these frequently appear despite successful removal of the primary growth, and given that they originate from the now no longer present tumour, the inescapable conclusion is that dissemination must have taken place prior to initial treatment. Failure to appreciate this rather obvious point results from shortcomings in available diagnostic technology, and inadequate usage of that which is available. Whether detected early or late, treatment of this disseminated cancer poses a common problem, and the various systemic methods are reviewed. Androgens, oestrogens, progestogens and single drug chemotherapy can, from time to time, produce useful results. By careful selection of patients with appropriate metastatic patterns, these methods may yield improved response rates up to 50% but, by and large, experience remains disappointing with across the board representative figures of perhaps 25% response being commonplace. Additionally, these methods are not without their side effects which can be distressing, and indeed on occasion life-threatening. Their short-comings have led to the development of cyclical combination chemotherapy as here reported. Cyclophosphamide, vincristine, 5-fluorouracil and methotrexate are administered for five consecutive days per month. The results obtained in 100 patients treated with this technique are compared with the authors' previous experience with norethisterone acetate and hypophysectomy. Whether the results are considered in total or broken down into prognostic categories such as predominant metastatic pattern, disease-free interval, or age, combination chemotherapy has a clear advantage over other techniques. Whilst this experience does not constitute a randomised trial, it is considered that the results are so superior to previous treatment techniques as to render such a study unnecessary or even unethical. It is proposed that combination chemotherapy should constitute the first line of treatment for overt advanced breast cancer. It is further proposed that its role should be explored at an earlier stage in the treatment of breast cancer. Before this can take place however, treatment must be made less demanding and less toxic. Further research is underway with these aims in mind.
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PMID:"Early" and "late" breast cancer: a unified concept for treatment. 100 Aug 91

Progesterone, like estrogens, is used in the treatment of metastatic breast cancer. The 3 most active derivatives are megestrol, norethisterone acetate, and medroxyprogesterone acetate (MPA). This study evaluates the use of MPA in treating metastatic breast cancer in 40 postmenopausal women (average age, 63 years; average duration of postmenopause, 14 years) who have either not responded to or have relapsed after therapy with estrogens and androgens. 18 patients received a depot preparation of MPA intramuscularly in a loading dose of 3.2 g over a 2-week period and then 400 mg at 2-4 week intervals. 22 patients received the drug orally in a dose of 200 to 300 mg daily. Patients were evaluated after 6 weeks of therapy. Criteria for evaluating response were those used by the Eastern Cooperative Oncology Group. Only 2 of 40 patients exhibited an objective response (disappearance of metastatic lymph node for 9 months in 1 and well-documented clinical improvement and control of brain metastases for 22 months in another). 2 patients had mixed responses of chest wall metastases (regression of some but not all lesions) lasting 3 and 4 months respectively. 5 patients had obvious subjective response (pain relief) but no objective response. Overall response rate was 22%: 4 objective responses (10%) and 5 subjectives responses (12%). Route of administration did not correlate with response. Tumor stimulation and clinical deterioration occurred in 4 patients. It appears that MPA therapy is costly and of minimal usefulness as secondary therapy in metastatic breast cancer. Further studies should focus on megestrol and norethisterone acetate which have been documented to have better response rates.
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PMID:Response to medroxyprogesterone acetate (NSC-26386) as secondary hormone therapy for metastatic breast cancer in postmenopausal women. 126 Jul 80

The effect of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and the cytokines interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) on matrix metalloproteinases (MMP) and metalloproteinase inhibitors was studied in a variety of human cell lines. Expression of the mammalian collagenase (MMP-1), 72-kD gelatinase/type IV collagenase (MMP-2), stromelysin (MMP-3), 92-kD gelatinase/type IV collagenase (MMP-9), and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) was assessed by zymography and Northern blot analysis. MMP-2 and TIMP-2 activities were refractory to TPA, IL-1 and TNF-alpha treatment in most of the cell lines. In contrast, MMP-3, MMP-9 and TIMP-1 activities were markedly stimulated by TPA in most of the tumor cell lines and human umbilical vein endothelial cells (HUVEC), whereas the fibroblast lines were minimally stimulated or unresponsive to TPA. The MMP-3, MMP-9 and TIMP-1 stimulation in response to IL-1 and TNF-alpha treatment was detected in some of the tumor cell lines and HUVEC. The increase in activity was less marked than in TPA. A breast carcinoma cell line, MDA-MB-231, which did not express MMP-2, had high expression of MMP-3 and MMP-9 which were unaffected by TPA and cytokine treatment. Northern blot analysis of MMP and TIMP mRNA expression reflected the zymogram findings for most of the cell lines. TPA-mediated stimulation of MMP-1 was similar to that of MMP-3 and MMP-9. Exceptions were the fibroblast cell lines which showed either a much more marked mRNA response of MMP-9 to TPA than observed at protein level, or a high constitutive MMP-9 mRNA when MMP-9 activity was not detectable by zymography. TPA-mediated stimulation of MMP-9 and TIMP-1 activity was blocked by staurosporine, an inhibitor of protein kinase C (PKC). A non-PKC-activating phorbol ester, 4 alpha-phorbol-12,13-didecanoate, did not stimulate MMP-9 and TIMP-1 activity. TPA treatment caused the increased expression of c-fos containing AP-1-specific binding activity in selected tumor cell lines. This activity was maximal at 6 h. An association was observed between AP-1 binding activity and increased expression of MMP-1, MMP-3 and MMP-9, which possess TPA-responsive elements (TRE). TPA-sensitive MMPs and TIMP-1 were variably stimulated by biologically relevant cytokines, such as IL-1 and TNF-alpha.(ABSTRACT TRUNCATED AT 400 WORDS)
Invasion Metastasis 1992
PMID:Effect of phorbol ester and cytokines on matrix metalloproteinase and tissue inhibitor of metalloproteinase expression in tumor and normal cell lines. 128 26

Visual assays were used to study the effect of phorbol myristate acetate (PMA) on the locomotion of lymphocytes from 14 patients with chronic lymphocytic leukaemia (CLL). Previous reports had shown that CLL cells from blood were defective in locomotor capacity and that adding PMA to the cells did not restore locomotion in a short-term (30 min) assay, but did stimulate unusual non-locomotor, multipolar, morphologies in a small proportion of the cells. Here we describe experiments in which CLL cells were cultured for 48 h in PMA. Many of the cells acquired locomotor morphologies with front-tail polarity which was unlike the short-term multipolar morphology. These cultured cells were also capable of locomotion and invaded collagen gels. Autoradiography suggested that after culture in PMA, the locomotory cells were the most active cells in 3H-uridine uptake. A computer analysis suggested that the cells in locomotor morphology were the same cells that increased in size. These findings suggest that, to acquire locomotor capacity, CLL lymphocytes require an appropriate signal to allow the cells to enter the cell cycle. During G1 the lymphocytes develop the capacity for locomotion. Long-term, but not short-term, culture in PMA provides such a signal but the mechanism by which it does so is unclear.
Invasion Metastasis 1992
PMID:Restoration with phorbol ester of a locomotor defect in human leukaemic lymphocytes: a visual study of chronic lymphocytic leukaemia cells. 138 Sep 53

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


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