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)

The role of UV radiation in the development of malignant melanoma has yet to be clearly defined. The purpose of these studies was to determine whether UV irradiation of mice produces local or systemic alterations that increase the in vivo growth of transplanted melanoma cells. K-1735 melanoma cells were injected into the external ears of syngeneic C3H mice. UV irradiation of the mice before or at the time of injection of the melanoma cells accelerated the appearance of the tumors. The effect was observed when melanoma cells were transplanted directly into the site of UV irradiation, but not when they were injected into an unirradiated site. The initial survival of radiolabeled melanoma cells at the site of inoculation was not altered by UV irradiation of the host, suggesting that the accelerated appearance of tumors was due to an increase in the clonogenic potential of cells injected into UV-irradiated skin. The effect of UV irradiation on the development of other syngeneic tumors was also investigated. The outgrowth of a second melanoma was also accelerated in UV-irradiated mice, whereas the growth of a UV-induced fibrosarcoma, a methylcholanthrene-induced fibrosarcoma, and a spontaneous hepatocarcinoma was not affected. These results suggest that, in addition to its carcinogenic activity, UV radiation may contribute to the incidence of cutaneous melanoma because of a local effect on the skin that stimulates melanoma development.
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PMID:Effect of ultraviolet-B radiation on the in vivo growth of murine melanoma cells. 338 94

Ornithine decarboxylase (ODC) is present in all nucleated cells and is the rate-limiting enzyme for synthesis of polyamines. In turn, the polyamines are required for DNA synthesis and cell growth. In Reuber H35 hepatoma cells, we show that ODC activity is increased by about 50% during exposure to a 1-h "athermal" (less than 0.1 degree C temperature rise) (450 MHz, 1.0 mW/cm2 peak-envelope-power) microwave field sinusoidally amplitude-modulated at 16 Hz. The increased activity of ODC persisted for several hours following the 1-h exposure to the field. A similar field amplitude-modulated at 60 and 100 Hz did not alter the hepatoma cell ODC activity. The stimulated ODC activity in the cultured cells that followed treatment with a phorbol ester tumor promoter (12-O-tetradecanoylphorbol-13-acetate) was further potentiated by prior exposure to the same low energy electromagnetic field. This field did not alter either basal or 12-O-tetradecanoylphorbol-13-acetate-stimulated DNA synthesis. We observed a similar increase in the basal ODC activity of cultures of two additional cell lines (Chinese hamster ovary; and 294T melanoma) exposed for 1 h to the amplitude-modulated field. Chinese hamster ovary cells exposed to the radio frequency field for 1 h also responded to subsequent treatment with 12-O-tetradecanoylphorbol-13-acetate by exhibiting a further increase in ODC activity. We have observed previously that the activity of this enzyme is increased in cultured cells following a transient exposure to a 60-Hz electric field. Altered ODC activity may serve as a sensitive and specific molecular marker of the transductive coupling of weak pericellular electromagnetic fields to biological systems.
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PMID:Increased ornithine decarboxylase activity in cultured cells exposed to low energy modulated microwave fields and phorbol ester tumor promoters. 339 Aug 16

Two 111indium-labeled murine monoclonal antibodies (MoAb), D3 and 9.2.27, directed to tumor antigens of L-10 hepatocarcinoma and human melanoma, respectively, selectively localized antigen-positive target cells in guinea pigs and nude mice. The fate of MoAb differed in the two antigen-antibody systems after reacting with their corresponding tumor antigens in vivo as reflected by patterns of distribution and turnover in vivo. The 9.2.27 localized in melanoma xenograft in nude mice after intravenous administration with slow loss from tumor but more rapid loss from normal tissues and thus demonstrated optimal imaging of small tumors (approximately equal to 5 mm) between 3 and 6 days after injection of the radiolabeled antibody. In contrast, D3 demonstrated a biphasic localization in guinea pig L-10 hepatocarcinoma with a maximal activity on the 2d day after administration and showed rapid loss from both tumor and normal tissues. Nonspecific localization of antibodies in liver and in kidney was found both in syngeneic (nude mice) and xenogeneic (guinea pig) hosts but was more pronounced in the xenogeneic species. These results indicate that the nature of the antigen-antibody interaction may be of importance in selecting MoAb for both diagnosis and therapy of malignant diseases.
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PMID:Dynamic interaction of 111indium-labeled monoclonal antibodies with surface antigens of solid tumors visualized in vivo by external scintigraphy. 345 73

The effects of a combined dietary restriction of tyrosine and phenylalanine on metastasis were investigated with the use of 3 rodent tumor cell lines: B16-bladder 6 (BL6) melanoma inoculated into (C57BL/6 X DBA/2)F1 mice, Lewis lung (3LL) carcinoma inoculated into C57BL/6 mice, and RT7-4bs hepatocarcinoma inoculated into BD-IV rats. When examined for effects on spontaneous metastasis, dietary restriction of tyrosine and phenylalanine had no effect on metastasis to draining lymph nodes in either BL6 or 3LL tumors. However, the restriction did reduce metastasis of RT7-4bs cells to draining lymph nodes by 60%. In all tumor systems, the dietary restriction effectively inhibited the subsequent growth of lymph node tumors. The most marked effect of the dietary restriction was on spontaneous hematogenous metastasis, which was almost totally blocked for BL6 cells and was reduced by 85% for RT7-4bs cells. Tumor-associated splenomegaly also was completely inhibited in 3LL tumor-bearing mice. The selective dietary amino acid restriction failed to reduce initial lung colonization in the experimental metastasis assay but clearly inhibited subsequent tumor outgrowth in the lungs. These findings demonstrate that modification of host nutritional status by restriction of the dietary intake of tyrosine and phenylalanine exerts a dramatic antimetastatic effect directed particularly on spontaneous hematogenous metastasis. Although the preliminary data suggest a primary modulating effect on tumor cell populations growing in diet-restricted animals to reduce inherent metastatic ability, the actual mechanisms remain to be defined.
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PMID:Dietary restriction of tyrosine and phenylalanine: inhibition of metastasis of three rodent tumors. 347 May 51

Recombinant human tumor necrosis factor (rHu-TNF) was found to exhibit potent antitumor activities not only against murine tumors, i.e. Meth A sarcoma, B 16 melanoma, colon 26 adenocarcinoma, Lewis lung carcinoma and MH134 hepatoma, transplanted in syngeneic mice but also against human tumors, i.e. HMV-2 melanoma, PC-10 lung carcinoma and GOTO neuroblastoma, heterotransplanted in nude mice. rHu-TNF caused necrosis of all tumors tested and inhibited their growth in a dose dependent manner. Complete regression of tumors was observed in mice bearing Meth A, B16, colon 26, MH134, HMV-2 and PC-10 but not in mice bearing Lewis lung carcinoma and GOTO neuroblastoma. The prolongation of survival time was also observed in syngeneic mice transplanted with murine tumors except Lewis lung carcinoma. The antitumor effect of rHu-TNF was more evident when it was given intratumorally than when given intravenously. The feasibility of rHu-TNF as a drug for cancer therapy is discussed.
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PMID:Recombinant human tumor necrosis factor--II. Antitumor effect on murine and human tumors transplanted in mice. 352 34

Recent phase II trials of cisplatin indicated a significant single agent activity on gastric cancer and non-Hodgkin lymphoma and, therefore, clinical usefulness in combination with other agents has been under investigation. Single agent efficacy on colorectal cancer and malignant melanoma is limited but investigation of combination regimens containing cisplatin is in progress to obtain additive or synergistic effect. Past results suggest some activity on pancreatic cancer and hepatoma. However, more data need to judge the effectiveness on both tumors.
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PMID:[Trials on expanding the clinical application of cisplatin]. 355 45

With the purpose of obtaining more potent and less toxic camptothecin (CPT) analogs, we prepared many derivatives of CPT. Among them, 7-ethyl-CPT (SN 22) and 7-ethyl-10-hydroxy-CPT (SN 38) showed strong antitumor activity with less toxicity. They were, however, insoluble and when they were made soluble, their activity was markedly diminished, as a result of cleavage of the delta-lactone ring. We therefore attempted to make soluble derivatives without breaking the delta-lactone ring and obtained 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxy-CPT (CPT-11), which showed very strong antitumor activity by i.p., i.v. or p.o. administration against the ascites type of L1210 leukemia, P388 leukemia, sarcoma 180, Meth A fibrosarcoma, B16 melanoma, Ehrlich carcinoma and MH134 hepatoma and the solid type of sarcoma 180, Meth A fibrosarcoma, Lewis lung carcinoma, C3H/HeN mammary carcinoma, Ehrlich carcinoma and MH134 hepatoma. The antileukemic activity of CPT-11 against L1210 was much higher than that of adriamycin. The acute toxicity of CPT-11 was extremely low, particularly in the case of oral administration, the LD50 being 765.3 mg/kg, 22 times greater than that of CPT-Na.
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PMID:[Antitumor activity of new derivatives of camptothecin]. 356 96

Four cases of malignant neoplasia in captive wild birds are described: an adenocarcinoma of the adrenal gland in a Mountain duck (Tadorna tadornoides), a malignant melanoma in the thoracic cavity of a Combed duck (Sarkidiornis melanotos), a hepatocellular carcinoma with pulmonary metastasis in an Asian Purple Swamphen (Porphyrio porphyrio), and an undifferentiated carcinoma in the abdomen with metastasis to skeletal muscle in a White-Breasted Waterhen (Amaurornis phoenicurus). The tumors were diagnosed during a 1-year period and represented an incidence of neoplasia of 3.1%. These appear to be the first documented cases of a malignant adrenal gland tumor and a non-ocular melanoma in the order Anseriformes. The hepatocellular carcinoma failed to react with an immunoperoxidase stain for alphafetoprotein.
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PMID:Four cases of neoplasia in captive wild birds. 357 89

Oxalato-platinum in a new platinum derivative which was found to be active in experimental tumors and devoid of nephrotoxicity. A phase I study was conducted in cancer patients according to a new design following the recommendations of our Institution's ethical committee to avoid the major drawback of classical phase I studies in which many patients receive the experimental drug at doses far under the potentially active dose extrapolated from experimental studies. The potentially active dose of l-OHP was determined from the Maximally Efficient Dose Range (MEDR) to be between 45 mg/m2 (subcurative dose) and 67 mg/m2 (subtoxic dose). The patients in this study received with increasing intervals 1/100, 1/10, 1/5, 1/3, 1/2, 2/3, 3/4, 1, of the low dose of the MEDR, this dose being reached after 90 to 120 days on study. 23 evaluable patients have entered the trial of which 19 reached the low dose of MEDR (45 mg/m2). Gastro-intestinal toxicity, nausea and vomiting, similar to those with CDDP occurred in all patients at or above the dose of 30 mg/m2. Renal toxicity was monitored with creatinine level and did not occur in any patient at any dose nor did significant hematologic toxicity occur. Thus nausea and vomiting appear to be the limiting toxicity of the drug. Responses were observed in this phase I study in lung cancer (1), breast cancer (1), melanoma (1) and perhaps hepatoma (major decrease in alpha FP levels) (1). The proposed starting dose for phase II studies is 45 mg/m2 but we plan to continue dose escalation during the phase II according to the design of Jones and Holland. This new study design allows each patient entering a phase I study to be treated with a potentially active dose of the drug studied.
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PMID:A phase I trial of trans-1-diaminocyclohexane oxalato-platinum (l-OHP). 358 May 5

Sensitivity of human serially transplanted tumours (melanoma, hepatoma, lung, stomach and bladder cancer) to monochemotherapy was studied in nude mice. The following groups of nude mice were examined: intact and those with human xenografts (control and mice treated with alkylating agents). Changes in peripheral blood morphology have been revealed and functional activity of the energetic enzymes (SDH and alpha-GPDH) has been cytochemically discovered.
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PMID:[Effect of chemotherapy on human tumor heterografts and lymphocytes in athymic mice]. 359 37


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