Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Modification of recombinant human interleukin 2 (rhIL-2) with monomethoxy polyethylene glycol has been shown to alter its pharmacokinetic properties. Therefore, we investigated the pharmacological parameters of schedule and dose in order to assess the impact on the in vivo antitumor activity of this modification. The antitumor efficacy, as well as the toxicity, of polyethylene glycol-interleukin 2 (PEG-IL-2) was compared to that of rhIL-2 in three transplantable syngeneic murine tumor models, Meth A fibrosarcoma, B16 melanoma, and Pan-02 pancreatic carcinoma. At equitoxic dose levels, the antitumor activity of PEG-IL-2 was far superior to that of rhIL-2 in all three tumor models. This efficacy of PEG-IL-2 was dose dependent and was greatest on a Q7D x 2 schedule in Meth A and B16. When the same total doses were further divided and delivered on any of several alternative schedules, either the efficacy was reduced or the toxicity of the treatments was increased. In Pan-02, a rhIL-2-resistant tumor, PEG-IL-2 treatment on either the Q7D x 2, Q4D x 3, or Q3D x 4 schedule resulted in approximately a 200% increase in lifespan; however, the toxicity of the treatment increased as the interval between doses was shortened. Simulations of the pharmacokinetic profiles of these various regimens suggested that the toxicity of PEG-IL-2 and rhIL-2 was related to the minimum plasma concentration that was obtained and the time interval between peak levels. The efficacy of the treatment was associated with the interleukin 2 plasma peak height, since a dose response was observed; however, peak plasma concentration did not appear to be the only parameter which determined efficacy. We hypothesize that this observed schedule dependence is also affected by the kinetics of the host's biological response to rhIL-2.
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PMID:Schedule dependency of the antitumor activity and toxicity of polyethylene glycol-modified interleukin 2 in murine tumor models. 281 8

Purified human natural tumor necrosis factor (n-TNF) was prepared by stimulating human leukemic B cell line (BALL-1) with Sendai virus. The colony formations of all of 18 human cancer-derived abnormal cell lines were suppressed by 10(1)-10(6) U/ml of n-TNF, while n-TNF was nontoxic to all human normal fibroblast cells. This in vitro inhibition of cell growth was reversible. In breast adenocarcinoma MCF7 cells treated with n-TNF a specific decrease of DNA synthesis was observed, and DNA histograms showed a block at G1 in the cell cycle. In vivo studies revealed that n-TNF suppressed the tumor growth of murine Meth A sarcoma, human renal adenocarcinoma (ACHN), malignant melanoma (SK-MEL-28) and glioblastoma (U-373 MG). Isobologram analysis showed that n-TNF synergistically inhibited cell growth in combination with human natural interferon (IFN)-a. In vivo synergism of n-TNF and IFN-a was also found in the U-373 MG tumor model implanted into nude mice.
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PMID:The inhibition of neoplastic cell proliferation with human natural tumor necrosis factor. 303 Sep 86

Interleukin 1 (IL1) has been suggested to have antitumor activity but there is no clear-cut evidence of an in vivo antitumor effect of pure IL1. In this work, the antitumor effect of purified recombinant human IL1 alpha (rHu-IL1 alpha) was assessed on murine tumors transplanted intradermally in syngeneic female mice. rHu-IL1 alpha inhibited the growth of Meth A sarcoma in BALB/c mice, B16 melanoma in C57BL/6 mice and colon 26 adenocarcinoma in CDF1 mice, as well as the spontaneous pulmonary metastasis of Lewis lung carcinoma in BDF1 mice, at intratumoral (itu), intramuscular (im), and/or intravenous (iv) doses ranging from 1 to 30 micrograms/mouse. The antitumor effect of rHu-IL1 alpha was generally dose- and route-dependent, being highest by the itu route, followed by the im and iv routes in that order. Palpable 7-day-old Meth A sarcoma was completely regressed in some mice given rHu-IL1 alpha itu once at doses of 10-30 micrograms/mouse (cured ratio; 71-100%), once a day for 3 days at doses of 3-30 micrograms/mouse (57-86%) or once a day for 7 days at doses of 1-10 micrograms/mouse (14-100%). Palpable 7-day-old B16 melanoma was also regressed completely in some mice given seven itu doses of 10-30 micrograms/mouse (14-86%). One-day-old Meth A sarcoma was more sensitive to rHu-IL1 alpha than 7-day-old Meth A sarcoma. There was no macroscopic sign of inflammation at the site of injection of rHu-IL1 alpha. These results show that rHu-IL1 alpha has antitumor activity in vivo and is worthy of further study as a potential antitumor agent.
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PMID:Antitumor effect of recombinant human interleukin 1 alpha against murine syngeneic tumors. 309 25

The combined effect of PT-050 (recombinant human TNF) and various antitumor drugs was investigated using murine colon 26 adenocarcinoma, Meth A sarcoma and B16 melanoma transplanted into syngeneic mice. When colon 26- or Meth A- bearing mice were intravenously given PT-050 in combination with mitomycin C (MMC), doxorubicin (DXR), cis-platinum (CDDP), 5-fluorouracil (5-FU) or cyclophosphamide (CPA), a significant synergistic effect was observed, that is, both the inhibition rate of tumor growth and the cured ratio were increased significantly when compared with those given each drug alone. Similarly, an augmentation of the antitumor effect was also observed in B16-bearing mice by a combined treatment with PT-050 and these antitumor drugs. These results suggest that the combination chemotherapy of PT-050 with various antitumor drugs may be useful for cancer therapy.
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PMID:[Combined effect of PT-050 (recombinant human TNF) and antitumor drugs on syngeneic murine tumors]. 309 17

Azinomycins A and B, isolated from the culture broth of Streptomyces griseofuscus S 42227, were examined for antitumor activities against P388 leukemia, P815 mastocytoma, B-16 melanoma, Ehrlich carcinoma, Lewis lung carcinoma and Meth A fibrosarcoma. Azinomycin B was markedly effective against the intraperitoneally inoculated tumors such as P388 leukemia, B-16 melanoma and Ehrlich carcinoma. The intraperitoneal administration of azinomycin B showed 57% survivors for 45 days and 193% ILS against P388 leukemia. For Ehrlich carcinoma, azinomycin B gave 161% ILS and 63% survivors for 45 days, but solid tumors such as Lewis lung carcinoma and Meth A fibrosarcoma were not susceptible to repeated injection of this substance. Azinomycin A was somewhat less effective than azinomycin B for the tumor systems tested.
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PMID:Azinomycins A and B, new antitumor antibiotics. III. Antitumor activity. 310 67

The chorioallantoic membrane of chick embryo was used to examine the chemosensitivity of the murine tumors, B16-F1 melanoma, B16-F10 melanoma, Meth-A fibrosarcoma, and Ehrlich carcinoma. The tumors were grown on the membrane, and the effects of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride, cyclophosphamide, dacarbazine, 5-fluorouracil, methotrexate, adriamycin, mitomycin C, vincristine, and cisplatin on the growth of the tumors were tested by iv injection into a vein of the chorioallantoic membrane or injection into the yolk sac. The use of chick embryo limits the time for drug exposure to 3 or 4 days, but Ehrlich carcinoma and Meth-A fibrosarcoma needed longer for the test; the use of irradiation from a cobalt source overcame the problem by increasing the growth rate of the grafts of these two tumors. There appeared to be a good correlation between the effects of the drugs on B16 melanomas grown in the eggs and in the original animals. Many compounds, including pro-drugs such as cyclophosphamide and dacarbazine, could be assayed in this way.
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PMID:Response to antitumor agents of murine transplantable tumors implanted onto chorioallantoic membrane of chick embryo. 311 99

Antitumor activity of Juzen-Taiho-Toh (JTX) and combination effect of JTX with antitumor agents were studied using murine tumors. In order to determine the antitumor activity of JTX, mice inoculated ip with IMC carcinoma (1 X 10(6) cells/CDF1 mouse), sarcoma-180(1 X 10(6) cells/ICR mouse) or Meth-A fibrosarcoma (1 X 10(6) cells/BALB/c mouse) were treated with JTX (12.5-50 mg/kg/day) ip on day 1 through day 10, and the survival days of mice were examined. Treatment with 25 mg/kg/day produced 38.7% increase of life span against IMC carcinoma. However, no antitumor effect was observed on solid form of these tumors by the daily treatment with JTX. Combination effect of JTX and antitumor agents was also examined. ICR mice inoculated sc with 1 X 10(6) cells of sarcoma-180 on day 0 were treated with JTX (2,000 mg/kg/day) po on day-7 through day 30. In addition, some of these groups received mitomycin C (5 mg/kg), cytoxan (67 mg/kg) or adriamycin (2.5 mg/kg) iv on days 3, 8 and 11, and the size of tumor grown in sc site was measured by a caliper. In combination with JTX, mitomycin C resulted in a significantly greater tumor growth inhibition than could be obtained with mitomycin C alone. Secondly, BALB/c or C57BL/6 mice inoculated sc with 1 X 10(4) cells of Meth-A fibrosarcoma or 1 X 10(5) cells of B16 melanoma on day 0 were treated with JTX (2,000 mg/kg/day) po on day 1 through day 30. Some of these group received ip with mitomycin C (3 mg/kg), adriamycin (2 mg/kg), 5-FU (33 mg/kg) or cytoxan (67 mg/kg) on days 3, 6, 9, 12, 15 and 18. From this result, the group treated with JTX and mitomycin C also showed a higher tumor-growth inhibition. Thus, a combination of a high dose of mitomycin C with JTX was more effective than mitomycin C alone.
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PMID:[Potentiation of chemotherapeutic activity by a Chinese herb medicine juzen-taiho-toh]. 313 Aug 6

In murine syngeneic tumor models, the antitumor effect of recombinant human interleukin-1 alpha (rHu IL-1 alpha) was significantly augmented by oral coadministration of indomethacin (IND). The augmentation was more or less observed by various routes of rHu IL-1 alpha (i.m., i.v., and intratumoral routes), against various tumors (Meth A sarcoma, colon 26 adenocarcinoma, B16 melanoma, and Lewis lung carcinoma) and irrespective of administration timings (in early and late stages of tumor growth). This results suggests that prostaglandin E2 produced by host cells in response to rHu IL-1 alpha and/or by tumor mass might interfere with the antitumor activity of rHu IL-1 alpha and also that cyclooxygenase inhibitors such as IND might counteract such interference. In the combination of rHu IL-1 alpha with IND, its efficacious doses (5-50 micrograms/kg) against murine tumors were at least 300-3000 times lower than its median lethal dose (more than 15 mg/kg). In addition, IND partially prevented the loss of body weight attributed to rHu IL-1 alpha injections at relatively high doses. Combined use of rHu IL-1 alpha with IND seems to be desirable from both therapeutic and toxicological viewpoints.
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PMID:Augmented antitumor effect of recombinant human interleukin-1 alpha by indomethacin. 325 68

Alkyllysophospholipids are analogs of the cell membrane component lysophosphocholine. The thioether lysophospholipid BM 41.440 (1-hexadecylmercapto-2-methoxymethyl-rac-glycero-3-phosphocholine) is already in use in phase I and II trials in human cancer therapy. A direct antitumor effect of this new compound has been shown in vitro using 35 different cell types of murine and human origin. All normal cells investigated were not affected in the concentration range (1-10 micrograms/ml) that was cytotoxic for most tumor cells studied. In vivo, antimalignant and antimetastatic actions have been documented in the Meth A sarcoma, L1210 leukemia, B 16 melanoma and the 3Lewis-lung carcinoma tumor models, respectively. Murine, bone marrow-derived macrophages (M phi), preincubated with BM 41.440, showed an increased cytotoxicity in vitro. Addition of syngeneic spleen cells and low doses of BM 41.440 to this system enhanced tumor cell destruction 20- to 100-fold compared to controls dependent on the target cells used (YAC, ABLS-8.1, L1210, and P815). In vivo, Meth A sarcoma growth was dose and time dependently reduced in CB6F1 mice under therapeutic IV application of BM 41.440-activated M phi. The mean survival time of DBA mice, treated once IP with BM 41.440 4 days before L1210 challenge, increased from 24 to 38 days.
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PMID:BM 41.440: a new antineoplastic, antimetastatic, and immune-stimulating drug. 348 59

Human recombinant interleukin 2 (IL-2) and tumor necrosis factor (TNF) were evaluated individually and in combination for their antitumor efficacy in vivo, using five s.c. murine tumors: L1210 leukemia, P815 mastocytoma, B16 melanoma, EL-4 lymphoma, and the methylcholanthrene-induced sarcoma, Meth A. While only the s.c. methylcholanthrene-induced tumor exhibited regression and/or cures in response to immunomodulatory therapy with either agent alone, the simultaneous administration of a maximally tolerated dose of TNF and IL-2 given daily from within 1 day (B16 melanoma), 3 days (L1210 leukemia and P815 mastocytoma) or 5 and 10 days (EL-4 lymphoma and methylcholanthrene-induced sarcoma) after tumor cell implant resulted in no tumor takes (growth). The TNF dose was apparently rate limiting in that reduction of the amount of TNF in the combination by 50% resulted in the loss of curative effects, while IL-2 doses could be reduced by 90% (depending upon tumor type) and still result in an efficacious combination. The synergy seen in combination IL-2 and TNF therapy appeared to be dependent upon tumor burden, but somewhat independent of tumor location. For example, no tumors were seen in the artificial pulmonary metastasis model of the B16 melanoma, and the percentage of extension of median lifetime (test versus control) greater than 150% was seen in the i.p. B16 melanoma, as well as several other i.p. models of the five tumor types. On the other hand, no significant extension of lifetime (greater than 150%) was seen with either lymphokine alone when administered i.p. at maximally tolerated dose for any of the five tumors tested here. Results are discussed in relation to potential immune modulatory events which may be occurring during combination treatments.
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PMID:Synergistic effects of combination therapy with human recombinant interleukin-2 and tumor necrosis factor in murine tumor models. 349 53


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