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 synthesis for cis-4,4' (1,2-cyclopropanediyl)bis(2,6-piperazinedione) (cis-3) is discussed. Stereoselective effects on metastases of cis-3 and the previously reported trans-2 isomer were compared to conformationally mobile ICRF-159 using a Syrian hamster lung adenocarcinoma (LG1002). Whereas ICRF-159 and cis-3 significantly inhibited lung metastases the trans-2 isomer significantly increased the number of metastatic nodules in the lung. Thus, these studies have revealed that, at least in one tumor model, antimetastatic activity can be separated from metastatic potentiating activity by controlling drug geometry.
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PMID:Stereoselective effects of cis- and trans-cyclopropylbis (dioxopiperazines) related to ICRF-159 on metastases of hamster lung adenocarcinoma. 72 27

The murine C1300 neuroblastoma model has been evaluated as a possible model for children with widespread metastatic disease. Drug toxicity studies were conducted in adult A/J mice with various doses of antitumor agents. Adriamycin, BCNU, bleomycin, guanazole, acronycine, isophosphamide, DTIC, ICRF-159, cyclophosphamide, vincristine, and vinblastine were adminstered intraperitoneally to random groups of normal mice. After identification of appropriate doses, chemotherapy studies were conducted with varius regimens of drugs. Chemotherapy was administered to adult A/J mice when their subcutaneously implanted tumors measured 1.0-1.7 cm in diameter. Antitumor drugs can be classified into three groups according to drug efficacy. BCNU, cyclophosphamide, and isophosphamide were extremely active. Cytosine arabinoside was reported to be active against this murine tumor in a previous publication. Drugs with minimal activiyt which deserve further evaluation included adriamycin, guanazole, ICRF-159, DTIC, and vinblastine. Inactive drugs were acronycine, bleomycin, 5-fluorouracil, and vincristine. These experiments suggest that children with metastatic neuroblastoma may respond to cyclophosphamide, isophosphamide, and BCNU, while DTIC, adriamycin, ICRF-159, guanazole, and the vinca alkaloids may also be effective. The results suggest that agents selected by the C1300 model should be given adequate clinical trials.
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PMID:Murine neuroblastoma: further evaluation of the C1300 model with single antitumor agents. 120

The effects of cytotoxic (cyclophosphamide, CCNU, GANU), antiinvasive (vincristine, vinblastine) and antimetastatic (ICRF-159, DM-COOK) agents have been compared in mice-bearing P388 and L1210 leukemias, and TLX5 lymphoma. The drugs tested increase the survival time of the treated mice in a manner consistent with a cytotoxic action in the case of cyclophosphamide, CCNU, GANU, vincristine and vinblastine. Leukemic infiltration of the brain after i.p. tumor implantation has been determined by bioassay of this organ, and is reduced by treatment with all of the drugs tested, with the exception of ICRF-159. DM-COOK appears to increase the life-span of the treated animals by the inhibition of leukemic spread rather than by a cytotoxic action. The marked cytotoxicity of vincristine and vinblastine is sufficient to account for failure to detect any antimetastatic effects of these agents. The lack of antidisseminative effect observed for ICRF-159 under the experimental conditions employed might be connected with the observation that the antimetastatic action of this drug on solid tumors is due to its effects on tumor blood vessels.
Clin Exp Metastasis
PMID:Effects of antimetastatic, antiinvasive and cytotoxic agents on the growth and spread of transplantable leukemias in mice. 295 Oct 46

The cytostatic and antimetastatic activities of 1,2-di(3,5-dioxopiperazin-1-yl) propane (ICRF-159, razoxane) were studied in a transplantable, slowly growing osteosarcoma in Sprague-Dawley rats. This tumor model is characterized by osteoid formation and spontaneous metastasization to lungs, kidneys and lymph nodes. Razoxane given intraperitoneally (i.p.) from 2 days before to 14 days after tumor transplantation (30 mg/kg or 10 mg/kg per day) resulted in a dose-dependent prolongation of median survival time (83 or 48 days respectively, versus 38 days for the control group), but showed no influence on the growth of the primary tumor. Early treatment with razoxane (30 mg/kg i.p. from day -2 to +14) showed a greater inhibition of pulmonary metastases than later treatment (30 mg/kg i.p. from day +14 to +28 after transplantation). Whereas 59.9 per cent of the total sectional area of the lungs in the control animals was covered by osteosarcoma metastases, only 3.4 per cent and 26.1 per cent respectively was affected in the early and late razoxane treatment groups. Toxic side-effects of these treatment schedules were reversible diffuse alopecia, but no retardation of body weight gain.
Clin Exp Metastasis
PMID:Antimetastatic effects of razoxane in a rat osteosarcoma model. 347 Jan 64

Two lines of Lewis lung carcinoma with a different potential to metastasize spontaneously to the lungs have been examined for their cytological and histological characteristics. Metastatic potential appears to be related with parenchymal organization of the primary tumours, since large haemorrhagic areas containing detached tumour cells and the absence of endothelialized capillaries are observed only in the line with high metastatic potential. At the same time, the cytological characteristics of the cells of the two tumour lines are similar, and do not seem to be related with metastatic potential. After treatment with the selective antimetastatic drugs ICRF-159 and DM-COOK, and with DTIC, the histological appearance of the line with high metastatic potential becomes similar to that of the line with low metastatic potential. These data seem to indicate that the early phases of tumour spread occurring in the primary tumour are of relevance for metastatic potential and control by antimetastatic drugs, and suggest that for DTIC such antimetastatic action may participate to its clinical antitumour effects.
Clin Exp Metastasis 1987 Sep
PMID:Morphological analysis of metastatic potential and antimetastatic drug effects in mice bearing two lines of Lewis lung carcinoma. 365 53

The therapeutic activity of the combined treatment with surgery and ICRF-159, measured in terms of increase of the survival time, has been tested in mice bearing two Lewis lung carcinoma lines having different potential to spontaneously metastasize (M1087 high; BM21548 low). As expected from the characteristics of this drug, a significant prolongation of the survival time of the treated hosts can be achieved only after presurgical treatment; the overall effect is greater using the tumor line with low metastatic ability. The response of the two tumor lines used to postoperative treatment with Cyclophosphamide also depends upon the tumor line used. The preoperative treatment of the animals with ICRF-159 markedly increases the response to Cyclophosphamide of the low responding M1087 line.
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PMID:Therapeutic activity of ICRF-159 combined with surgery: effects of postsurgical treatment with cyclophosphamide in mice bearing Lewis lung carcinoma lines. 406 52

We have investigated the effect of ICRF-159 on the toxicity of daunorubicin (DR) and doxorubicin (DX) given iv, and the effectiveness of ICRF-159 combined with DR or DX on the growth of transplantable MLV-M (murine leukemia virus-Moloney) leukemia, MS-2 solid sarcoma, and pulmonary MS-2 metastases in mice. The injection of ICRF-159 concurrently with the administration of DR resulted in a marked decrease in the toxicity of the antibiotic. However, when DX was injected concurrently with ICRF-159 an increase in antibiotic toxicity was observed, except when ICRF-159 was employed at a very low dosage. ICRF-159 administered alone did not influence the tumor growth in the systems tested and did not result in antimetastatic activity. In mice bearing transplanted MLV-M leukemia, the effects of the combination of ICRF-159 with DR or DX were not superior to those of DR or DX treatment on either tumor growth or lifespan. The treatment of MS-2 tumor with the ICRF-159 and DX combination neither produced a therapeutic synergism (therapeutic response superior to the maximum response obtainable by either agent independently) nor antagonized the antineoplastic action of DX. A marked inhibition of tumor growth and increase in lifespan were observed in the mice treated with a high dose of DR (10 mg/kg/injection) plus ICRF-159 (50 mg/kg/injection). We have also examined, on MS-2 lung metastases, the effectiveness of surgical-adjuvant combination chemotherapy with DR or DX plus ICRF-159 injected at different times with respect to surgery. A synergistic effect of DX or DR with ICRF-159 was observed when the drug treatment was performed before the surgery, or both before and after the surgery. No synergistic effect of DX or DR with ICRF-159 on MS-2 lung metastases was found when the MS-2 lung metastases were treated after the surgery. A higher antimetastatic activity was observed in the groups treated with a combination of toxic doses of DR and ICRF-150 than in the groups treated with a combination of toxic doses of DR and ICRF-159 than in the groups treated with tolerated doses of the antibiotic.
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PMID:Studies in mice treated with ICRF-159 combined with daunorubicin or doxorubicin. 626 70

The development and characterisation of a new epithelial model for the experimental investigation of metastasis is described. A tissue culture cell line CMT64 was established from a spontaneous alveolar lung carcinoma of a 17 month old female C57BL/ICRF at mouse (Franks et al., 1976). Subcutaneous inoculation of cells produces local tumours which give rise to a small number of lung metastases within three weeks. Four different tissue culture sublines CMT167, 170, 175 and 181 with increased metastatic ability were selected from pooled lung metastases by culture, mouse inoculation and reselection from lung metastases through four culture/inoculation cycles. These sublines are themselves heterogeneous and clones derived from them display marked differences in metastatic behaviour. Both CMT64 and its sublines have remained relatively stable in morphology and behavior since their origin, are fairly well differentiated, produce basal lamina even in metastases, and metastasise rapidly and preferentially to the lung after subcutaneous and intravenous inoculation in both syngeneic C57 and Nu/Nu mice (Franks & Layton, 1984). The expression of the metastatic potential of these cells is strongly influenced by the age and immune status of the host. The CMT64 system is a particularly useful model for experimental metastasis studies.
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PMID:Heterogeneity in a spontaneous mouse lung carcinoma: selection and characterisation of stable metastatic variants. 632 36

The selective antimetastatic agents p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (DM-COOK), 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) and (+/-)1,2-di(3,5-dioxopiperazin-1-yl)propane (ICRF-159) have been shown to markedly depress the formation of spontaneous hematogenous metastases in mice bearing s.c. Lewis lung carcinoma, with a mechanism unrelated to cytotoxicity for tumor cells. The effects on hemostasis of DM-COOK, DTIC and ICRF-159 have thus been examined in comparison with those of a purely cytotoxic agent, cyclophosphamide, in mice bearing i.m. Lewis lung carcinoma. The parameters considered are the number of platelets and their aggregability, prothrombin and partial thromboplastin times, plasma fibrinogen concentration and tumor cell procoagulant activity. Slight variations are caused by drug treatment in tumor-bearing mice as compared with untreated tumor-bearing controls; the pattern of effects of the selective antimetastatic agents does not differ from that of the reference cytotoxic compound used, cyclophosphamide. These data thus indicate that the effects on hemostasis of the drugs examined can contribute only marginally to their antimetastatic action, since more pronounced effects on hemostasis have been shown to be required to significantly affect metastasis formation.
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PMID:Hemostasis and mechanism of action of selective antimetastatic drugs in mice bearing Lewis lung carcinoma. 654 Jan 95

Circulating tumor cells can be detected by means of flow cytometry in the blood of mice bearing i.m. Lewis lung carcinoma. This technique can be applied in the case of aneuploid tumors and does not require either concentration of nucleated cells or other processing of the blood samples. It offers the advantages of simplicity and speed and allows quantitative measurement of the number of circulating tumor cells. It can be applied to the study of the effects of drug treatment on the number of circulating tumor cells, for those drugs which do not cause alterations in the nuclear DNA content of normal diploid blood cells. The number of circulating tumor cells determined by flow cytometry is markedly reduced by treatment with ICRF-159, by dimethyltriazene DM-COOK, and also by its clinically used analog, DTIC.
Clin Exp Metastasis
PMID:Effects of DTIC, DM-COOK and ICRF-159 on the number of circulating Lewis lung carcinoma cells detected by flow cytometry. 654 95


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