Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

173 patients with regional lymphatic metastases (n = 139) or distant disease (n = 34) were prospectively randomised, following resection of all clinically detectable tumour, to observation (n = 88) or adjuvant chemotherapy (n = 85). The treatment group received 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) 80 mg/m2 intravenously (i.v.) every 4 weeks, and actinomycin-D 10 micrograms/kg, vincristine 1.0 mg/m2 i.v. every 2 weeks for 6 months. The disease-free survival curves between the two groups were significantly different (P = 0.03). The estimated 5-year disease-free survival rate for the observation group was 9% and for the treatment group 29%. However, the overall survival curves were not significantly different for the two groups. Nitrosoureas may have a weak effect as adjuvant treatment in malignant melanoma.
 ...
PMID:Adjuvant chemotherapy with a nitrosourea-based protocol in advanced malignant melanoma. 826 Feb 35

Tetrahydrocortisol, beta-cyclodextrin tetradecasulfate, and minocycline used alone or in combination are not very cytotoxic toward EMT-6 mouse mammary tumor cells growing in monolayer. Tetrahydrocortisol (100 microM, 24 h) and beta-cyclodextrin tetradecasulfate (100 microM, 24 h) protected EMT-6 cells from the cytotoxicity of CDDP, melphalan, 4-hydroperoxycyclophosphamide, BCNU, and X-rays under various conditions of oxygenation and pH. Minocycline (100 microM, 24 h) either had no effect upon or was additive with the antitumor alkylating agents or X-rays in cytotoxic activity toward the EMT-6 cells in culture. The combination of the three modulators either had no effect upon or was to a small degree protective against the cytotoxicity of the antitumor alkylating agents or X-rays. The Lewis lung carcinoma was chosen for primary tumor growth-delay studies and tumor lung-metastases studied. Tetrahydrocortisol and beta-cyclodextrin tetradecasulfate were given in a 1:1 molar ratio by continuous infusion over 14 days, and minocycline was given i.p. over 14 days, from day 4 to day 18 post tumor implantation. The combination of tetrahydrocortisol/beta-cyclodextrin tetradecasulfate diminished the tumor growth delay induced by CDDP and melphalan and produced modest increases in the tumor growth delay produced by cyclophosphamide and radiation. Minocycline co-treatment increased the tumor growth delay produced by CDDP, melphalan, radiation, bleomycin, and, especially cyclophosphamide, where 4 of 12 animals receiving minocycline (14 x 5 mg/kg, days 4-18) and cyclophosphamide (3 x 150 mg/kg, days 7, 9, 11) were long-term survivors. The 3 modulators given in combination produced further increases in tumor growth delay with all of the cytotoxic therapies, and 5 of 12 of the animals treated with the 3-modulator combination and cyclophosphamide were long-term survivors. Although neither tetrahydrocortisol/beta-cyclodextrin tetradecasulfate, minocycline, nor the three modulator combination impacted the number of lung metastases, there was a decrease in the number of large lung metastases. Treatment with the cytotoxic therapies alone reduced the number of lung metastases. Addition of the modulators to treatment with the cytotoxic therapies resulted in a further reduction in the number of lung metastases. These results indicate that agents that inhibit the breakdown of the extracellular matrix can be useful additions to the treatment of solid tumors.
 ...
PMID:beta-cyclodextrin tetradecasulfate/tetrahydrocortisol +/- minocycline as modulators of cancer therapies in vitro and in vivo against primary and metastatic Lewis lung carcinoma. 826 4

Thirty-two patients with metastatic melanoma received combination chemotherapy and hormonal therapy. Treatment included Carmustine, Cisplatin, Dacarbazine and Tamoxifen (BCDT). The overall response rate was 47%: five patients had a complete response (16%), 10 patients had a partial response (31%) and two had no response (6%). The median survival for responders was 10 months (range 2-20). The BCDT regimen was equally effective against soft tissue and visceral metastases. Neither survival or response rate was modified by pretreatment with alpha-interferon (alpha-IFN). In agreement with the results of a recent randomized trial comparing the efficacy of Dacarbazine with that of Dacarbazine plus Tamoxifen, a better survival was found in women than in men: although the response rate was identical (47%), the median duration of response was higher for women. A fall in serum soluble IL-2 receptor (sIL-2R) levels after therapy was seen in responding patients, confirming the usefulness of this parameter in monitoring disease evolution.
 ...
PMID:Therapy for metastatic melanoma: effective combination of dacarbazine, carmustine, cisplatin and tamoxifen. 851 51

We have analysed the chemosensitivity of 121 human melanoma metastases in the 6-day mouse subrenal capsule assay (SRCA). A total of 13 different chemotherapy regimens were analysed in four successive series. By the original criteria of the assay, 75% of tumours were sensitive to at least one regimen. The most effective combinations, giving sensitivity rates > 40%, were of dacarbazine, vincristine, and BCNU (DOB) with or without metronidazole, followed by cisplatin plus etoposide (Plat-VP16) combined with interferon. On the basis of the SRCA screening we developed a four-drug chemotherapy regimen combined with interferon for metastatic melanoma. Retrospectively analysed the assay correctly identified 77% of clinical responders and 54% of clinical non-responders. The overall predictive accuracy was 65%. Despite the limitations of the assay, it can be used for screening new drugs or combinations.
 ...
PMID:Chemosensitivity of human melanoma metastases in mouse subrenal capsule assay--can it predict tumour response to combined cytostatic plus interferon therapy in metastatic melanoma? 881 24

The phase I trial in breast cancer conducted by Peters et al. defined a regimen of high-dose chemotherapy consisting of cyclophosphamide, cisplatinum and BCNU (CPA/cDDP/BCNU). In chemotherapy-resistant metastatic disease, 23% of patients achieved complete remission followed by early relapse. In a phase II study, 53% of stage IV patients with no prior treatment achieved complete response (CR) with 16% progression-free at five to nine years post-transplant. Chemically debulking with an Adriamycin, 5FU, and Methotrexate regimen (AFM) to minimal tumor burden achieved 68% CR, with approximately 20% disease-free patients at 36 months. Other high dose chemotherapy regimens have been developed, again demonstrating in stage IV patients complete remissions in excess of 65% and progression-free survival rates of 20-30%.
 ...
PMID:Positive selection and ex vivo expansion of hematopoietic progenitors as autografts for high-dose chemotherapy, potential importance in patients with bone metastases. 885 28

The treatment of patients with advanced stage (stage III and IV) melanoma remains discouraging. Except for the study using tamoxifen, combination chemotherapy (cisplatin, DTIC, BCNU), plus biological therapy (IFN-alpha and/or IL-2), which achieved a 57% response rate, virtually any combination of agents or modalities yielded response rates of only 20% to 30%, and none are effective in central nervous system metastases. Durable clinical cures in patients with advanced-stage disease are extremely rare and can probably be attributed more to host defense mechanisms than iatrogenic intervention. The future in treatment then can only look promising to immunologists, molecular biologists, and clinicians striving to elucidate the biological mechanisms isolated patients have for destroying melanoma cells and incorporating those mechanisms into therapeutics for the remainder of melanoma victims.
 ...
PMID:Melanoma: epidemiology, pathogenesis, and new modes of treatment. 890 99

Local chemotherapy with biodegradable polymers prolongs survival with minimal morbidity in patients with intracranial high-grade gliomas. However, use of local chemotherapy for metastatic brain tumors has not been defined. We studied the safety and the efficacy of locally delivered chemotherapy with and without concurrent radiation therapy in treating tumors that frequently metastasize to the brain. The chemotherapeutic agents 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), carboplatin, and camptothecin were incorporated into controlled-release polymers and tested individually against intracranial challenges with one of four tumors (lung carcinoma, renal cell carcinoma, colon carcinoma, and melanoma). For each combination of drug and tumor type, four groups were tested: (a) empty polymer (no drug); (b) external beam radiotherapy (XRT) alone; (c) local chemotherapy from biodegradable polymer alone; and (d) local chemotherapy and XRT together. Polymers were implanted 5 days after tumor inoculation; XRT was given on days 7-9 (300 cGy/day). BCNU and XRT together were effective against all four tumors. BCNU polymer alone significantly prolonged survival in mice with intracranial melanoma or renal cell carcinoma. Carboplatin alone was effective against both melanoma and colon carcinoma and in combination with XRT against colon and renal cell carcinomas. Camptothecin was effective only with XRT against melanoma. These studies demonstrate that local delivery of chemotherapy with concurrent radiation therapy is safe and can significantly prolong survival in models of common intracranial metastatic tumors. Concurrent use of local chemotherapy with standard XRT appears to be more effective than either treatment alone. Local chemotherapy may also be of benefit to patients who have previously received maximal cranial irradiation but suffer an intracranial recurrence.
 ...
PMID:Local delivery of chemotherapy and concurrent external beam radiotherapy prolongs survival in metastatic brain tumor models. 891 60

Melanoma is rare in Singapore with an age-standardised rate (ASR) of 0.4-0.8 per 100,000 per year. Thirteen patients with metastatic or locally advanced melanoma were referred to the Department of Medical Oncology, Singapore General Hospital between Feb 1991 and Nov 1993. Ten patients were given combination chemotherapy comprising carmustine (BCNU), cisplatin, dacarbazine (DTIC) and tamoxifen. The remaining 3 patients either rejected chemotherapy or were too ill to receive chemotherapy. Patient characteristics were as follows: there were 6 males and 4 females; age range 29-75 years; all were Chinese; sites of primary disease: extremities 8, retroorbital 1, vagina 1; sites of metastases: lymph nodes 6, skin 2, pulmonary 3, liver 1. All received the same combination chemotherapy comprising iv BCNU 150 mg/m2 q8wk, iv DTIC 220 mg/m2 x 3 days q4 wk, iv cisplatin 25 mg/m2 x 3 days q4 wk and tab tamoxifen 40 mg daily. There were 6 partial responses and no complete responses, giving a response rate of 60% with a median survival of 11.5 months. Three patients with sites of disease in the vagina, retroorbital region and metastatic liver disease had progressive disease despite chemotherapy and one died of treatment related sepsis. The 6 responders include those with metastases to the skin, nodes and/or lung. Treatment was generally tolerable. Two patients experienced delays of their subsequent cycles of treatment by 1-2 weeks due either to neutropenia and/or thrombocytopenia. This regimen is a fairly active combination against metastatic melanoma, particularly those with metastases to the nodes, skin and the lung. Those with involvement of other sites tend to respond poorly.
 ...
PMID:Combination chemotherapy (dacarbazine, carmustine, cisplastin, and tamoxifen) in advanced melanoma. 894 55

One hundred nineteen patients with relapsed or refractory Hodgkin's disease (HD) received high-dose therapy followed by autologous hematopoietic progenitor cell transplantation. Three preparatory regimens, selected on the basis of prior therapy and pulmonary status, were employed. Twenty-six patients without a history of prior chest or pelvic irradiation were treated with fractionated total body irradiation, etoposide (VP) 60 mg/kg and cyclophosphamide (Cy) 100 mg/kg. Seventy-four patients received BCNU 15 mg/kg with identical doses of VP and Cy. A group of 19 patients with a limited diffusing capacity or history of pneumonitis received a novel high-dose regimen consisting of CCNU 15 mg/kg, VP 60 mg/kg and Cy 100 mg/kg. Twenty-nine patients (24%) had failed induction therapy and 35 (29%) had progressive HD within 1 year of initial chemotherapy. At 4 years actuarial survival was 52%, event-free survival was 48% and freedom from progression (FFP) was 62%. No significant differences were seen in survival data with the three preparatory regimens. Six patients died within 100 days of transplantation and 5 died at a later date of transplant-related complications. Secondary malignancies have developed in 6 patients, including myelodysplasia/leukemia in four patients and solid tumors in two patients. Regression analysis identified systemic symptoms at relapse, disseminated pulmonary or bone marrow disease at relapse and more than minimal disease at the time of transplantation as significant prognostic factors for overall and event-free survival and FFP. Patients with none of these factors enjoyed an 85% FFP at 4 years compared with 41% for patients with one or more unfavorable prognostic factors (P = .0001). Our results confirm the efficacy of high-dose therapy and autografting in recurrent or refractory HD. Although longer follow-up is necessary to address ultimate cure rates and toxicity, our data indicate that a desire to reduce late effects should drive future research efforts in favorable patients whereas new initiatives are needed for those with less favorable prognoses.
 ...
PMID:High-dose therapy and autologous hematopoietic progenitor cell transplantation for recurrent or refractory Hodgkin's disease: analysis of the Stanford University results and prognostic indices. 902 11

Matrix metalloproteinases (MMPs) play an important role in various physiological and pathological conditions such as tissue remodeling, and cancer cell invasion and metastasis. The aim of this study was to determine the effect of the antitumor compounds cis-dichlorodiammine platinum (ii) (cisplatin) and 1, 3 bis (2-chloroethyl)-1-nitrosourea (BCNU) on 72-kDa type IV collagenase activity (MMP-2) in human gliomas. Human glioblastoma cell lines were treated with cisplatin (25 microM), and BCNU (50 microM), and the levels of MMP-2 were estimated in serum-free conditioned medium and in cell extracts at different time intervals. Gelatin zymography revealed increased levels of MMP-2 in serum-free conditioned medium and in cell extracts of untreated glioblastoma cell cultures during a 72-h period. In contrast, MMP-2 levels were significantly decreased in cisplatin-treated cells both in conditioned medium and cell extracts. However, no significant changes of MMP-2 levels were noted in BCNU-treated cells. Quantitative analysis of MMP-2 enzyme activity by densitometry and amount of MMP-2 protein by ELISA showed significantly decreased levels of MMP-2 in cisplatin-treated cells compared to BCNU and untreated glioblastoma cells. The results indicate that decreased levels of MMP-2 might represent an additional mechanism by which cisplatin provides its antineoplastic effects.
Clin Exp Metastasis 1997 Jul
PMID:Effect of cisplatin and BCNU on MMP-2 levels in human glioblastoma cell lines in vitro. 921 24


<< Previous 1 2 3 4 5 6 7 8 Next >>