Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transplantability of mouse tumors superinfected with various kinds of membrane viruses was investigated in syngeneic hosts. Methylcholanthrene-induced fibrosarcomas in BALB/c mice, Meth A, and in C57BL/6 mice, BMT-, superinfected with Friend lymphatic leukemia virus in mice given neonatal injection of the virus, grew more slowly than uninfected tumors. The retardation of growths was not observed in mice that had been given injections of the virus at birth. Similarly, Meth A and a hepatoma in C3H/He mice, MH134, superinfected with Moloney murine sarcoma virus in nu/nu mice, had reduced their transplantability in respective syngeneic mice. Further, Meth A and MH134 superinfected with endogenous rat leukemia virus and human measles virus, respectively, in nu/nu mice also showed reduced transplantability, and some of the former were actually rejected by normal syngeneic hosts. On the other hand, the reduced transplantability was not found in irradiated mice, suggesting that the phenomenon was due to immunological events. However, a myelogenous leukemia in C57BL/6 mice, C1498, superinfected with Moloney sarcoma virus in nu/nu mice grew like uninfected tumor and did not show reduced transplantability at all.
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PMID:Reduced transplantability of syngenic mouse tumors superinfected with membrane viruses in nu/nu mice. 100 77

We have successfully generated cytotoxic monoclonal antibodies against a rat histiocytoma, AK-5. Monoclonal antibodies obtained after fusing immunized rat splenocytes with SP2/0 myeloma, were cytotoxic to AK-5 cells in the presence of complement. These monoclonals were highly specific and did not show any cross reactivity with normal cells and ascitic tumors such as Zajdela ascites hepatoma or Meth A. One of the antibodies was conjugated to daunomycin and used in the chemotherapeutic treatment. Total regression of AK-5 histiocytoma was obtained after injection of daunomycin-MAb conjugate into tumor bearing animals suggesting the specific targeting of the antineoplastic drug to the tumor. The histology of the tumor sections showed extensive necrosis of the tumors after treatment of the animals with drug-MAb conjugate.
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PMID:Generation of cytotoxic monoclonals against AK-5 histiocytoma: conjugation with daunomycin and use in chemotherapy. 131 80

A low-toxic lipopolysaccharide (BP-LPS) was isolated from killed Bordetella pertussis (Tohama strain). LD50 of BP-LPS was about 0.8 mg/mouse which was about 10-fold higher than the LD50 of E. coli-LPS(80 micrograms/mouse). Toxicity measured by decrease in body weight of BP-LPS-injected mice was similarly low. BP-LPS had strong antitumor activities against various murine syngeneic tumors, and its systemic administration caused clear regression of such as MM46 mammary carcinoma and Meth A fibrosarcoma. It is noteworthy that a tolerable dosage of BP-LPS (375 micrograms/mouse) showed clear antitumor activity against MH134 hepatoma, which is known to be insusceptible to usual types of BRM including bacterial LPS. These findings suggest that BP-LPS is a promising candidate as an antitumor agent for clinical use. Biological activities of BP-LPS were examined and compared with those of toxic LPS extracted from Escherichia coli and other enterobacteria. Activation or stimulation of macrophages and lymphocytes by these LPS, including TNF induction, was found to be similar. However, activation of human or murine neutrophils, as estimated by neutrophil-adherence assay in vitro, though induced by all other toxic LPS tested, was not induced by BP-LPS. This inability of BP-LPS to activate neutrophils is assumed to be related to its low toxicity.
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PMID:BRM activities of low-toxic Bordetella pertussis lipopolysaccharides. 141 7

We evaluated the antitumor effect of an interleukin 2 (IL-2) slow delivery system, the IL-2 mini-pellet, in two murine solid tumor models, and also investigated the enhancement of its therapeutic effect by serial administration. The IL-2 mini-pellet contains 1 x 10(6) units of IL-2 and releases it slowly in vivo. In our experiment, the IL-2 mini-pellet was administered subcutaneously near the tumor site in combination with the intravenous injection of lymphokine-activated killer (LAK) cells. When this regimen was given on days 8 and 11 after the subcutaneous inoculation of Meth A fibrosarcoma into BALB/c mice, tumor growth was significantly inhibited (p less than 0.05) compared to tumor growth in untreated controls. Moreover, the IL-2 mini-pellet alone was also effective in inhibiting tumor growth. In another experiment, MH134 hepatoma was inoculated into C3H/He mice. Both administration of the IL-2 mini-pellet alone and in combination with LAK cells resulted in complete tumor regression in four of five mice. In a third experiment, serial administration of the IL-2 mini-pellet at 3- or 5-day intervals prolonged the suppression of Meth A fibrosarcoma growth in BALB/c mice. These results suggested that the IL-2 mini-pellet could be applied to cancer immunotherapy and that its antitumor effect could be prolonged by serial administration.
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PMID:Augmentation of antitumor effect on syngeneic murine solid tumors by an interleukin 2 slow delivery system, the IL-2 mini-pellet. 185 89

We have shown the in vivo usefulness of a novel chimera tumor necrosis factor (TNF), called rTNF-STH, which was constituted with human thymosin beta 4 and recombinant human TNF-SAM1. Tumor necrosis was induced by intravenous injection of a smaller amount of rTNF-STH (1 x 10(3) U/mouse, 0.67 microgram/mouse) than rTNF-alpha or rTNF-S (1 x 10(4) U/mouse, 2.5-5 micrograms/mouse). Significant antitumor effects of rTNF-STH to Meth A fibrosarcoma, B16 melanoma, MH134 hepatoma, or Lewis lung carcinoma (3LL) were observed by systemic injection of rTNF-STH at the maximum tolerable dose of 1 x 10(4) U/mouse (6.7 micrograms/mouse); this dose did not cause regression of tumors by conventional rTNF-alpha. rTNF-STH showed a significant prolongation of its half-life in serum. The average calculated half-life of the chimera protein is about 110 min, which is 15 times longer than that of original TNF-SAM1 (7.5 min). On the basis of this prolongation of half-life of rTNF-STH and its efficient hemorrhagic necrotic activity, the antitumor effect of rTNF-STH--as compared with that of the known TNF species--is discussed. Findings indicate that use of the chimera protein to alter the N-terminal region of TNF may be a promising approach to obtain molecules that more favorably attack tumors and other diseases than conventional rTNFs.
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PMID:Antitumor activity of a novel chimera tumor necrosis factor (TNF-STH) constructed by connecting rTNF-S with thymosin beta 4 against murine syngeneic tumors. 204 90

The effect of intraperitoneal administration of OK-432 followed by intraperitoneal instillation of recombinant interleukin-2(rIL-2) was examined in tumor bearing animals and in four recurrent gynecological cancer patients with peritonitis carcinomatosa which had been resistant to chemotherapeutic drugs. Seven days after intraperitoneal inoculation of tumor cells (10(6) cells/body of MH134 hepatoma into C3H/He mice and 10(5) cells/body of Meth-A fibrosarcoma into BALB/C mice, respectively), OK-432 was administered intraperitoneally. Two days later, a 14 day course of daily intraperitoneal instillation of rIL-2 followed. The survival time for animals treated with OK-432 combined with rIL-2 was significantly prolonged. Three of the 8 C3H/He mice and one of the 8 BALB/C mice in this group survived more than 150 days without forming ascites. However, the group treated by rIL-2 alone did not survive for more than 40 days. The group treated by OK-432 alone as well as the untreated group did not survive for more than 20 days. Ascitic fluid disappeared clinically in two of four cases and decreased in the rest. Ascitic cancer cells disappeared in one case and decreased in three cases. The serum CA125 level declined significantly in all cases. The surface markers of ascitic lymphocytes were analyzed by flow cytometry on day 8. The CD4+ subset accounted for 70-90% whereas the CD8+ subset accounted for only 7-17%. In three cases in which two color analysis was performed, the CD4+, CD29+ helper inducer T cell was dominant. We could conclude that LAK cells were not the main effector cells.
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PMID:[The effect of intraperitoneal administration of OK-432 with recombinant interleukin-2 to patients with peritonitis carcinomatosa of recurrent gynecological cancer and changes in ascitic lymphocyte subsets]. 205 23

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

This study reported that acute toxicity (expressed as the LD50 value) of rTNF-SAM1 and rTNF-SAM2 which we constructed was considerably lower than that of rTNF-alpha (1). Following this finding, the antitumor effects of systemic administration of these novel recombinant tumor necrosis factors (TNF-S) (named rTNF-SAM1 and rTNF-SAM2) were examined in vivo on murine tumors (Meth A fibrosarcoma, MH134 hepatoma, and B16 melanoma). Both rTNF-SAM1 and rTNF-SAM2 could be administered systemically to tumor-bearing mice at doses up to 3 X 10(4) to 10(5) U. Growth of all tumors was significantly inhibited by systemic administration of rTNF-SAM1 or rTNF-SAM2 at a dose of greater than 3 X 10(4) U; at this dosage conventional rTNF-alpha could not be administered systemically to any of the mice strains due to its toxicity. These results confirm our previous finding that the rTNF-SAM group can be administered with safety at higher doses than rTNF-alpha, and revealed that these novel rTNF-S could be more promising antitumor drugs than rTNF-alpha in view of their lower toxicity compared with antitumor effect.
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PMID:Antitumor effect of systemic administration of novel recombinant tumor necrosis factor (rTNF-S) with less toxicity than conventional rTNF-alpha in vivo. 274 98

Chemically induced sarcomas of murine origin are characterized by the expression of unique tumour-specific transplantation antigens. Their nature and the genetic basis of their antigenic diversity are unknown. Numerous attempts have been made to relate these antigens to products of known polymorphic gene families. A serological analysis of cell-surface antigens of sarcomas was initiated on the premise that serologically defined unique tumour-specific antigens would be related to tumour-specific transplantation antigens. This analysis led to the serological definition of two noncross-reacting tumour-specific antigens on two antigenically distinct BALB/c sarcomas, Meth A and CMS4. Assignment of the gene(s) involved in expression of the Meth A antigen to the distal region of chromosome 12, the same region encoding Igh, raised the possibility that genetic elements responsible for antibody idiotype could be involved in the antigenic diversity of tumour-specific transplantation antigens. Although several studies indicate a concordant expression of the Meth A and the tumour-specific transplantation antigen, the Meth A tumour-specific transplantation antigen identified as an 82,000-Da protein does not express the serologically defined antigen. This is in contrast to the Zajdela hepatoma of rat origin, where a serologically defined tumour-specific antigen is related to the tumour-specific transplantation antigen. Whether the serologically defined Meth A antigen has tumour-specific transplantation antigen activity is not presently known.
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PMID:Cell surface antigens of chemically induced sarcomas of murine origin. 302 22

Enough amounts of tumor necrosis factor (TNF) in mice serum for the therapy were observed by treatment with 100 units of recombinant human TNF-alpha (rHuTNF-alpha) followed by administration of OK-432 (a streptococcal preparation). Optimal time interval between rTNF and OK-432 to produce endogenous TNF was 3 h, and priming activity of rTNF persisted for at least 10 h. The same effect was observed using novel human recombinant TNF-SAM2 (rHuTNF-SAM2) developed by our group. Production of endogenous TNF using rTNF-alpha or rTNF-SAM2 as a priming reagent was almost equal among various mice strains. Induced TNF in mice serum was completely neutralized by anti-MuTNF antiserum, but not by anti-HuTNF monoclonal antibody. rMuTNF could also induce the priming state; however, the dose-response kinetics of the priming effect to produce endogenous TNF was different between rHuTNFs and rMuTNF-alpha, suggesting species specificity among rTNFs used. The therapeutic effect against Meth A and MH134 tumors in mice treated by rHuTNFs in combination with OK-432 was superior to that by single administration of either OK-432 or rHuTNFs or by successive administrations of OK-432. Especially, the antitumor effect against MH134 hepatoma was superior to that of any other treatment using known biological response modifiers so far experienced. These results suggest that such combination antitumor therapy as rTNF together with OK-432 should be applicable to cancer patients.
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PMID:TNF induces endogenous TNF in vivo: the basis of EET therapy as a combination of rTNF together with endogenous TNF. 321 23


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