Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This work examines the variation with oxygen tension (pO2) of the individual spin-lattice relaxation times (T1) of the 19F resonances of the perfluorocarbon emulsion Oxypherol-ET (FC-43). A linear relationship between 1/T1 and pO2 has been confirmed for all four resonances at any specific temperature. Using a saturation recovery sequence, T1 has been successfully measured using surface coil NMR spectroscopy. This has facilitated measurement of T1 in vivo in a subcutaneous murine tumor. Mice were predosed with Oxypherol-ET emulsion: following complete vascular clearance of the perfluorocarbon, 19F signal was observed specifically from material sequestered in tissue, thus avoiding flow artifacts. Comparison of the pO2 estimated from each of the 19F resonances provided an internal consistency check. A pO2 = 0.1 +/- 2.2% was determined in a Meth-A murine tumor. When the mouse breathed carbogen (95% O2, 5% CO2) no significant change in tumor pO2 was detected, whereas the pO2 in the liver showed a distinct increase.
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PMID:Tissue oxygenation: a novel determination using 19F surface coil NMR spectroscopy of sequestered perfluorocarbon emulsion. 206 43

Mitogenicity, lethal toxicity, induction of tumor necrotizing factor (TNF), and antitumor activity against Meth A fibrosarcoma of four chemically synthesized lipopentapeptide analogs, S-[2,3-bis(palmitoyloxy)-2R (designated as KAB-1), -2S(KAB-3)-propyl]-N-palmitoyl-(R)-cysteinyl-(S)-seryl- (S)-seryl-(S)-asparaginyl-(S)-alanine, S-[2,3-bis(palmitoyloxy)-2R(KAB-2), and -2S(KAB-4)-propyl]-N-[(2,2,2)-trichloroethoxycarbonyl]-(R)- cysteinyl-(S)-seryl-(S)-seryl-(S)-asparaginyl-(S)-alanine, of bacterial lipoprotein were investigated. These four analogs, as well as bacterial lipopolysaccharide (LPS) or synthetic Escherichia coli-type lipid A (506), were capable of increasing of [3H]thymidine into splenocytes of C3H/He mice. Although LPS and 506 did not exhibit the mitogenic activity in C3H/HeJ mice, KAB compounds showed remarkable mitogenicity. These analogs did not show the lethal toxicity at a high dose of 50 micrograms/mouse in galactosamine-loaded C57BL/6 mice. Peritoneal macrophages, stimulated with four analogs, caused the production of TNF which induces the L929 cell lysis in vitro. Twice, intravenous injections of 50 micrograms/mouse of these analogs showed weak growth inhibition of Meth A fibrosarcoma in BALB/c mice. The inhibitory effect of KAB-2 compound, which caused the strong TNF-induction among the four analogs, was the most potent. These results indicate that the biological activity of KAB-2 (R-configuration of the C-2 position in glycerol moiety with dipalmitoyl) is stronger than that of the other three analogs.
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PMID:Comparison of biologic activities of synthetic lipopentapeptide analogs of bacterial lipoprotein in mice. 206 59

Orally administered muramyl dipeptide (MDP) was found to prime induction of endogenous tumor necrosis factor (TNF) in mice. This priming effect was observed after oral administration of MDP of more than 100 micrograms/mouse; the maximal time interval between oral administration of MDP and i.v. injection of OK-432, a triggering agent for induction of endogenous TNF, was extended over 3-10 h and then decreased after 24 h. Antitumor effect against Meth-A, MH134, and MM46 tumor cells in mice was observed after oral administration of MDP followed by i.v. injection of OK-432. These findings suggest that orally administered MDP can be used as a priming agent for inducing endogenous TNF in cancer patients, and that MDP, a component of enteric bacteria, must have an important role in maintaining homeostasis through activation of macrophages.
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PMID:Priming effect of orally administered muramyl dipeptide on induction of endogenous tumor necrosis factor. 207 43

Tumor necrosis factor (TNF) induces hemorrhagic necrosis in the Meth A mouse tumor model and has shown cytostatic and cytotoxic antitumor effects against a wide range of human tumors both in vitro and as human tumor xenografts in nude mice. Because of in vitro activity against colorectal tumors and antitumor responses in colon cancer patients in phase I trials, this phase II study was undertaken. Patients were treated with TNF administered daily for 5 days/week every other week at a dose of 150 micrograms/m2/day as a 30-min i.v. infusion. One cycle consisted of 4 weeks of treatment over an 8-week period. Twenty-five patients have been entered into this study with three patients ineligible. The 22 eligible patients ranged in age from 38-73 years and had initial performance status of 0 in 10 patients, 1 in 10 patients, and 2 in 2 patients. No complete or partial responses were seen. Two patients had stable disease (no response) and 18 patients progressed. Two patients had no evaluation and were assumed to have had no response. The response rate is therefore 0%, with a 95% exact confidence interval of 0% to 15%. There was one grade 4 toxicity consisting of nausea and vomiting. Most common grade 3 toxicities were chills and fever in four patients, nausea and vomiting in three patients, and anemia and elevated liver enzymes in two patients. Headache, myalgia/arthralgia, and elevated serum triglycerides were frequently seen. Mildly elevated levels of fibrin split products were seen after TNF treatment in 5/13 evaluable patients and one ineligible patient.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A phase II trial of recombinant tumor necrosis factor in patients with metastatic colorectal adenocarcinoma: a Southwest Oncology Group study. 207 44

With the object of providing an oligomeric prodrug of 5-fluorouracil (5FU) with reduced side-effects, affinity for tumor cells and high antitumor activity, 5FU was covalently attached to three chito-oligosaccharides (COS) through hexamethylene spacer groups via carbamoyl bonds. The ability of these conjugates to prolong the life of lymphocytic leukemia mice (following their intraperitoneal administration) and their tumor-inhibitory effects on Meth-A fibrosarcoma or MH-134 hepatoma mice (following their subcutaneous administration) were assessed. The conjugates caused a significant increase in the survival time of the p-388 leukemia mice, and higher growth-inhibitory effects against the solid tumor than either 5FU, COS, or blends of 5FU and COS. At the highest dose levels, the conjugates did not cause acute toxicity, and did not cause rapid decrease in body weight.
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PMID:Synthesis and antitumor activity of conjugates of 5-fluorouracil and chito-oligosaccharides involving a hexamethylene spacer group and carbamoyl bonds. 208 29

The effect of a non-protein fraction from an extract of inflamed skin of rabbits inoculated with vaccinia virus (Neurotropin, NSP) was studied on Meth A tumor-induced delayed type hypersensitivity (Meth A-DTH) in BALB/c mice. NSP enhanced the Meth A-DTH. NSP also enhanced the DTH suppressed with 5-fluorouracil (5-FU). Moreover, NSP inhibited the fatal effect of 5-FU and restored the decrease of body weight caused by 5-FU. However, NSP reduced partially but significantly the suppression of the tumor growth by 5-FU. NSP may be useful for cancer treatment in combination with chemotherapeutic agents, if NSP does not inhibit their antitumor activity.
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PMID:Effect of a non-protein fraction from an extract of the inflamed skin of rabbits inoculated with vaccinia virus (Neurotropin) on Meth A-induced delayed type hypersensitivity. 208 10

The state of active immunity to Meth A fibrosarcoma in mice immunized with an admixture of Meth A cells and Propionibacterium acnes is associated with possession by the host of spleen cells capable of producing interferon-gamma (IFN-gamma) upon in vitro restimulation with irradiated tumor cells. The ability of spleen cells from immunized mice to produce IFN-gamma in response to irradiated Meth A cells decays as active antitumor immunity is replaced by a state of immunological memory. The IFN-producing cells are L3T4+Ly2+, cyclophosphamide-sensitive and radiosensitive T cells, as determined by their sensitivity to corresponding monoclonal antibodies and complement. The induction of IFN-gamma production by in vivo tumor-sensitized T cells is tumor specific, in that spleen cells from mice immunized against Meth A fibrosarcoma can produce IFN in response to irradiated Meth A cells but not in response to another syngeneic tumor M109 lung carcinoma.
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PMID:Production of interferon-gamma by in vivo tumor-sensitized T cells: association with active antitumor immunity. 210 80

We examined the modification of host T cells of tumor nodules by interferon (IFN) therapy in mouse models. The host cells were recovered from regressing tumor nodules of mice at Day 13 after intradermal tumor inoculation at Day 0 and administration of 5 x 10(5) U/mouse/day IFN at Day 6 to Day 10. These host cells neutralized in vivo Meth A growth in a dose-dependent fashion. In vitro treatment of these cells with anti-Thy 1.2 monoclonal antibody and rabbit sera as a source of complement abrogated their tumor-neutralizing activity, but only partially, indicating that both T cells and non-T cells were involved in tumor neutralization. The finding that host cells from regressing tumor nodules of either Meth A or Meth 1, an antigenically distinct fibrosarcoma, neutralized both Meth A and Meth 1 tumors without much selectivity was consistent with possible non-T cell involvement. Most of these characteristics of host cells of regressing nodules of IFN-administered mice were also noted with host cells of progressing nodules of placebo-administered mice and there was no significant difference in neutralizing activity qualitatively or quantitatively between the two sources of host cells. There was no significant difference in host T and B cell numbers and compositions of regressing and progressing nodules either. These essentially negative findings raise the possibility, among others, that the primary target host cells to be modified by IFN were not T cells, although the therapeutic effect of IFN was dependent on the host T cells.
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PMID:Antitumor activity of host T and non-T cells recovered from tumor nodules after interferon therapy. 211 93

Meth A sarcoma, growing in the subcutaneous tissue of syngeneic BALB/c mice, regressed completely after an intraperitoneal (ip) injection of proteose peptone (PP) (on day 6) followed by 2 ip administrations (on days 7 and 8) of human recombinant interleukin-2 (IL-2, 25 micrograms/day), whereas one such treatment alone had little effect on the tumor growth. While this combination treatment was effective in anti-asialo GM1 antibody-treated mice, no such effect was noted in T cell-depleted ATXFL (thymectomized, irradiated and fetal liver cell-reconstituted) mice. These results show that T cells are mainly responsible for this antitumor effect. Treatment with a combination of PP and IL-2, but not with either PP or IL-2 alone, resulted in a marked increase in the T cell population in the peritoneal cavity after the treatment. At an early stage after the combination treatment, both peritoneal exudate cells (PEC) and spleen cells exhibited killing activity with a promiscuous specificity. However, at a later stage, 7 days after the treatment, Meth A-specific killer activity was observed in both PEC and the spleen. Meth A rechallenge was rejected by the mice in which the tumor had regressed, but the antigenically different Meth 1 was accepted by them. A similar result was obtained in Winn's neutralization test. These results suggest that this combination treatment, which is effective in the generation of lymphokine-activated killer cells in the peritoneal cavity, finally resulted in the induction of tumor-specific killer cells in the periphery. These results clearly show the anti-tumor efficacy of combination treatment with PP and rIL-2.
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PMID:Combination treatment with irritant and recombinant interleukin 2 in the peritoneal cavity for evoking effective anti-tumor activity: generation of lymphokine-activated killer cells and tumor-specific killer cells. 211 94

This investigation was conducted to provide preclinical in vivo tumor response data collected under standardized conditions with a range of clinically useful drugs combined with type I (alpha/beta) or type II (gamma) interferon. Murine tumor models used were P388 leukemia, Meth A sarcoma, and B16 melanoma. Eleven cytotoxic drugs were studied. Interferon combinations with cytosine arabinoside provided consistent indications of activity greater than that of the respective single agents. Doxorubicin and cisplatin each prolonged the time to treatment failure, relative to single-agent results, when they were combined with gamma-interferon in the Meth A and B16 models. Interferon combinations with methotrexate, 6-mercaptopurine, 6-thioguanine, ampligen, suramin, 5-fluorouracil, cyclophosphamide, and vinblastine yielded no evidence of any positive therapeutic interactions under the conditions of this study.
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PMID:Evaluation of combinations of interferons and cytotoxic drugs in murine tumor models in vivo. 211 61


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