Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Antimetastatic effects of razoxane in a rat osteosarcoma model. 347 Jan 64

The effect of an antimetastatic agent plus intratumor chemotherapy was evaluated in mice bearing Lewis-lung carcinoma by measuring survival time and by histological examination. Polymeric flavan-3,4-diol (APF) from avocado seeds, Persea gratissima, administered alone directly into the tumor did not change survival time, although it partially destroyed the primary tumor. However, the drug administered in combination with an antimetastatic, 1,2-bis(3,5-dioxopiperazin-1-yl)ethane (ICRF-154), resulted in an increase in survival time. When 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) was used in place of polymeric flavanadiol as an intralesional drug, a significant increase in survival was also achieved. The effect of each drug alone and of their combination was evaluated by "responder analyses". Animals "cured" by the combination and rechallenged with 2 X 10(6) tumor cells showed that immunization could occur.
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PMID:Intratumor chemotherapy in combination with a systemic antimetastatic drug in the treatment of Lewis-lung carcinoma. 383 80

Three Lewis lung carcinoma lines (3LL) with different metastatic behavior have been investigated with regard to their response to Razoxane (ICRF-159). The effects of different schedules were tested both on primary and secondary tumors. Results show that the lines are heterogeneous in their response to this antimetastatic agent and that, in particular, BM21548 the least metastatic line is also less sensitive to ICRF-159. A better response can be achieved with this line by a proper fractionation regimen which takes into account the delayed metastasis release from primary tumor. As far as M1087, the most metastatic line is concerned, secondaries are greatly affected by ICRF-159 treatment if performed at a moderately advanced stage of growth. On the contrary, metastases from early tumor stages can be better controlled by radical surgery of the primary implant than by treatment with ICRF-159.
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PMID:Lewis lung carcinoma lines with different metastatic behavior: response to ICRF-159. 671 81

Rat prostate adenocarcinoma III (PA III) cells metastasize spontaneously from extravascular implant sites through ipsilateral lymphatic channels to the lungs in which they develop as distinct expanding foci of tumors. ICRF-159 (30 + 60 mg/kg body weight) was administered to rats with PA-III cells at daily intervals from day 0 to 2 weeks (5 days/week). When the rats were examined after 35 and 40 days, the drug treatment caused a significant suppression of the primary tumor and of metastatic dissemination. When the treatment schedule with ICRF-159 was delayed to day 18 in rats with metastasizing PA III cells, the progress of metastasis was thereafter interrupted or retarded significantly. Rats with PA II cells which metastasize in fulminant pattern through lymphatic and blood channels to multiple target organs were administered ICRF-159 (60 mg/kg body weight) from day 0 for over 2 weeks. They did with disseminated tumors within days after cessation of treatments.
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PMID:Interference with in vivo growth and metastasis of prostate adenocarcinoma (PA-III) by ICRF-159. 727 10

The R3327 MAT-LyLu, a lymphotrophic, metastatic prostate-derived rat tumor was treated with high dose diethylstilbestrol or the chemotherapeutic agent ICRF-159. Both drugs inhibited the growth of the primary tumor and the development of metastases.
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PMID:Effect of high dose diethylstilbestrol and ICRF-159 on the growth and metastases of the R3327 MAT-LyLu prostate-derived tumor. 730 51

Bisdioxopiperazines, including ICRF-154 and razoxane (ICRF-159, Raz), are a family of anticancer agents developed in the UK, specifically targeting neoplastic metastases. Two other bisdioxopiperazine derivatives, probimane (Pro) and MST-16, were synthesized at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. In order to determine the similarities and differences between these agents in medical chemistry, we evaluated the anti-tumor and anti-metastatic effects of Pro and MST-16 in vitro and in vivo against a number of human tumor cell lines and one of murine origin (Lewis lung carcinoma, LLC), and one human tumor xenograft (LAX-83) in nude mice. Our results show that Pro was cytotoxic to human tumor cell lines in vitro (IC50 < 50 microM for 48 h), approximately 3 to 20-fold more than MST-16. Pro and MST-16 manifested more prolonged cytotoxicity than some other first-line anticancer drugs including 5-fluorouacil, vincristine and doxorubicin, and maintain their cytotoxic effects for 4 days in vitro. In animal experiments, Pro and Raz were active against primary tumor growth (35-50 %) and significantly inhibited pulmonary metastasis of LLC (inhibition > 90 %) at dosage below LD(5). Both Raz and Pro were effective in administration schedules of 1, 5 and 9 days. Both Raz (25-32 %) and Pro (55-60 %) caused statistically significant inhibition of the growth of LAX 83 (a human lung adeno-carcinoma xenograft) in nude mice. In this model, Pro was more effective against LAX83 than Raz at equitoxic dosages. These findings suggest that Pro is active against more categories of tumors both in vivo and in vitro, which in some circumstances may make it superior to the currently-used anticancer bisdioxopiperazines, including razoxane and MST-16.
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PMID:Medicinal chemistry of probimane and MST-16: comparison of anticancer effects between bisdioxopiperazines. 1684 48