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)

Hemorrhage is a recognized occurrence in hepatocellular carcinoma but is infrequently seen with tumors metastatic to the liver. This complication was observed in three patients with primary hepatic malignancy and in four patients with hepatic metastases (melanoma, two; colon, one; breast, one) who were studied by CT. Hemorrhage occurred in the patient with metastatic colon carcinoma in the setting of anticoagulation. Definitive radiographic signs of hemorrhage were detected by CT in six of the patients, including hyperdense hepatic masses on noncontrast scans (four patients), high density peritoneal (one patient) and subcapsular fluid (one patient), and the hematocrit effect in peritoneal fluid (one patient). In three patients an irregular liver border adjacent to perihepatic fluid suggested the liver as the organ from which bleeding originated. There were four deaths, none of which was immediately related to the hemorrhagic complication.
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PMID:CT features of hemorrhagic malignant liver tumors. 282 Oct 89

The factors influencing survival for patients with cancer of the liver were studied by reviewing the records of 414 patients operated on in a private oncology practice. Approximately half (47%) had colorectal metastasis; 17% had metastatic breast carcinoma, 14% had malignant hepatoma, 5% had metastatic melanoma, and the remainder had a variety of primary cancers. Eighty-two per cent of all patients had advanced liver disease when first diagnosed. One quarter of the patients had some type of resection; the remainder had abdominal exploration plus insertion of an infusion catheter into the hepatic artery. The postoperative mortality rate after liver resection for 108 patients was 6.5%. After resection, the most important prognostic factor influencing survival was the presence or absence of extrahepatic metastases. When possible, resection was by far the best treatment available, and the best results were seen in patients who had resection of a solitary lesion. For advanced disease, when resection was not possible, intra-arterial chemotherapy, primarily with 5-fluorouracil (5-FU), was associated with response rates of 36% for colorectal cancer, 45% for breast cancer, 13% for hepatocellular cancer, 12% for melanoma, and 14% for metastases from other primary sites. The patients who responded to infusion lived longer than those who did not respond. For example, at 18 months, 26% of the responders with colorectal cancer were alive, as were 50% of the responders with breast cancer and 40% of the responders with hepatocellular cancer. In contrast, at 18 months, there were no survivors among the nonresponders with colorectal, breast, or hepatocellular cancer. For those patients treated solely by infusion chemotherapy, the extent of disease in the liver was the most reliable factor in predicting the length of survival. However, very few patients treated in this manner lived longer than 3 years.
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PMID:Treatment of cancer of the liver. Twenty years' experience with infusion and resection in 414 patients. 283 23

Recent studies in animal models involving antibody tumor targeting of hepatoma and melanoma and clinical trials involving hepatoma patients have suggested that preirradiation of tumors may enhance antibody tumor targeting. These reports led us to study the effect of external irradiation on monoclonal antibody (MAb) targeting of human carcinomas; as a model system, we used MAb B72.3 and the LS-174T human colon carcinoma xenograft in athymic mice. LS-174T tumors exposed to 300 cGy grew to approximately 93% the size of non-irradiated tumors, while those exposed to 600, 900, or 2,000 cGy were approximately 41% the size of control tumors. Splitting the 900 cGy into three 300-cGy fractions yielded a two-fold lower tumor volume compared with a single 900-cGy fraction. Histochemical evaluation of the carcinomas revealed a decrease in the number of mitoses per high power field consistent with early effects of radiation exposure. Using the avidin-biotin complex immunoperoxidase technique, carcinomas were assayed for expression of the tumor associated glycoprotein (TAG)-72, the high-molecular-weight mucin detected by MAb B72.3. No discernable variation was observed in the staining intensity among tumors in both the control and radiation treated group; that is, differences among tumors within each group were compatible with the known heterogeneous expression of TAG-72. Exposure of carcinomas to 300 or 900 cGy in a single fraction or 900 cGy split in three 300-cGy fractions did not yield a consistent or substantial enhanced localization of radiolabeled MAb B72.3 IgG or F(ab')2 to tumors. A 1.5-fold augmentation of MAb binding to tumors was observed in preirradiated mice; however, these results were not statistically significant. Inherent differences in tumors such as cell type of origin, size, spatial configuration, extent of vascularization and volume of interstitial space may contribute to variability of the effect of preirradiation of tumors on antibody binding. Our results suggest that consistent augmentation of radiolabeled antibody localization to tumors is not a universal phenomenon.
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PMID:Studies concerning the effect of external irradiation on localization of radiolabeled monoclonal antibody B72.3 to human colon carcinoma xenografts. 292 Nov 70

A novel antitumor compound, N-beta-dimethyl-aminoethyl 9-carboxy-5-hydroxy-10-methoxybenzo[a]-phenazine-6-carboxamide sodium salt (NC-190) was evaluated for its antitumor activity in experimental murine tumor systems. In the initial studies with P388 leukemia (i.p.-i.p.), NC-190 led to an increase of greater than 200% in life span (ILS), and 75% of the mice were alive on day 30, when the optimal dose (50 mg/kg, days 1-5) was given. Additionally, the compound had significant activities against i.p. inoculated mouse L1210 leukemia, B16 melanoma, M5076 reticulum cell sarcoma, sarcoma 180, mouse hepatoma MH134, and rat Yoshida sarcoma and Yoshida ascites hepatoma AH130. The optimal dose resulted in a greater than 280% ILS with a 30-day survival of 50% in mice with L1210 leukemia (100 mg/kg, days 1-5), a 156% ILS in mice with B16 melanoma (50 mg/kg, days 1-5), a 98% ILS with a 90-day survival of 25% in mice with M5076 reticulum cell sarcoma (25 mg/kg, days 1, 5, 9, and 13), a greater than 300% ILS with a 60-day survival of 50% in mice with sarcoma 180 (50 mg/kg, days 3-10), a 148% ILS with a 60-day survival of 25% in mice with MH134 (25 mg/kg, days 1-5), a 129% ILS with a 60-day survival of 12.5% in rats with Yoshida sarcoma (12.5 mg/kg, day 3-10), and a greater than 161% ILS with a 60-day survival of 50% in rats with AH130 (6.3 mg/kg, days 3-10). In the experiments with s.c. inoculated tumors, NC-190 not only inhibited tumor growth, but also increased the life span of mice with Lewis lung carcinoma or B16 melanoma. The 60-day survivors accounted for 60% and 30% in mice with Lewis lung carcinoma and B16 melanoma, respectively. The compound significantly inhibited the spontaneous lung metastasis of Lewis lung carcinoma by more than 90% when eight daily i.v. injections were given. NC-190 was active by the i.p., s.c., and i.v. routes. Five consecutive daily i.p. doses (days 1-5) were more effective than a single dose (day 1), two doses (days 1 and 5), or three doses (days 1, 5, and 9). NC-190 warrants further study as a potential antineoplastic agent against human neoplasms, as it has a broad spectrum of antitumor activity and inhibits metastasis.
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PMID:In vivo activity on murine tumors of a novel antitumor compound, N-beta-dimethylaminoethyl 9-carboxy-5-hydroxy-10-methoxybenzo[a]phenazine-6-carboxamide sodium salt (NC-190). 292 70

Relative amounts of mRNA for cathepsin B were measured in normal murine liver and three murine tumors, an invasive liver tumor (hepatoma, Hepa cl 9) and two melanoma variants (B16-F1 and B16 amelanotic melanoma, B16a). Using a human cDNA to the cathepsin B coding region as a hybridization probe, we detected two species of cathepsin B specific RNA transcripts (2.2 and 4.1 kb) in total RNA preparations of all four tissues. The concentrations of the 2.2 and 4.1 kb species were 3.6 and 2.7-fold greater in the highly metastatic B16a melanoma than in normal liver. The concentration of the 2.2 kb species in the invasive hepatoma was 1.7-fold greater than in normal liver. The increased levels of the 2.2 kb message were reflected in increases in activity of cathepsin B in both Hepa cl 9 and B16a.
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PMID:Enhanced levels of cathepsin B mRNA in murine tumors. 292 10

Thirteen endothelial cell growth factors have been purified to homogeneity by heparin affinity and reversed-phase high performance liquid chromatography, and their chromatographic and electrophoretic properties were compared. The amino acid compositions of 10 of these mitogens have also been determined. The results indicate that these heparin-binding growth factors (HBGFs) can be subdivided into two classes. Class 1 HBGFs are anionic mitogens of molecular weight 15,000-17,000 found in high levels in neural tissue and include acidic brain fibroblast growth factor and retina-derived growth factor. Class 2 HBGFs are cationic mitogens of molecular weight 18,000-20,000 found in a variety of normal tissues and are typified by pituitary fibroblast growth factor and cartilage-derived growth factor. Typical class 2 HBGFs have also been isolated from a rat chondrosarcoma, a human melanoma, and a human hepatoma, suggesting that tumors do not make a structurally distinct HBGF class. These results provide a sound basis for the evaluation of the HBGFs purified from a variety of tissues and species and for the delineation of their normal and pathological functions in vivo.
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PMID:Purification and characterization of heparin-binding endothelial cell growth factors. 300 88

The antitumor effects of 5 different subtypes of human type I interferons (IFN-alpha(Le), rIFN-alpha A, rIFN-alpha D, IFN-beta, and rIFN-beta) were studied on 3 human cancer cell lines (Daudi lymphoma, PLC/PRF/' hepatoma, and G361 melanoma). IFN-alpha(Le) was the most potent against Daudi cells. The effects of IFNs were cytostatic. On the other hand, 500 IU/ml of IFN-alpha(Le), IFN-beta and 5000 IU/ml of rIFN-beta showed cytocidal effect against PLC/PRF/5 cells. The G361 cells were the least sensitive to the IFNs tested. This is the first report on the antitumor effect of rIFN-beta isolated from insect cells. The effect of this rIFN-beta was similar to that of IFN-beta.
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PMID:Comparison of the antitumor effects of human natural and recombinant interferons (alpha and beta) on human cancer cell lines. 301 84

The data on 26 patients with solitary metastatic lesions arising in cortical bone were studied. Nineteen patients were over 50 years of age. In 19 patients, the cortical metastasis was the first indication of the presence of a primary malignant condition. In seven cases, cortical metastases developed in patients with a known primary tumor. The primary tumors involved were eight renal cell carcinomas, six bronchogenic carcinomas, two carcinomas of the gastrointestinal tract, one osteosarcoma, one neuroblastoma, one melanoma, one hepatoma, one carcinoma of the breast, and one thyroid carcinoma. In four cases, the primary tumor remained unknown. A metastatic origin should be considered in the differential diagnosis of an osteolytic lesion arising in the cortex of a long bone, especially in older patients and in patients with a known primary malignant condition. The cortical bone metastases encountered in this study did not originate solely from bronchogenic carcinoma, as has been reported by other authors. Cortical metastases are probably less rare than has been hitherto assumed.
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PMID:Cortical bone metastases. 317 2

We report that IL 1 acts on the endothelium, inducing a long-lasting increase in its adhesivity to tumor cells. Selective pretreatment of cultured human umbilical vein endothelial cells (EC) with IL 1 caused a significant increase in adhesion of three human colorectal carcinoma (HT-29, HCC-P2988, and HCC-M1410) cell lines and one human melanoma (A-375) cell line. Tumor necrosis factor (TNF) was as effective as IL 1 in promoting tumor cell adhesion to EC, whereas IFN gamma and IL 2 were inactive. The IL 1 and TNF induction of EC adhesivity was both concentration (threshold concentration 1 U/ml) and time dependent (peak 4-6 h), reversible within 24 h, and blocked by a protein synthesis inhibitor. The IL 1 and TNF action on EC may play a role in tumor cell lodgement.
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PMID:Interleukin 1 promotes tumor cell adhesion to cultured human endothelial cells. 326 29

FK973, a new, substituted dihydrobenzoxazine (11-acetyl-8-carbamoyloxymethyl-4-formyl-14-oxa-1,11- diazatetracyclo[7.4.1.0.0]tetra-deca-2,4,6-trien-6,9-diyl diacetate), was obtained by chemical modification of a novel antibiotic which was isolated from the fermentation products of Streptomyces sandaensis No. 6897. FK973 had cytotoxic effects against in vitro cultured human and murine tumor cells. FK973 in doses of 0.032-5.6 mg/kg (i.p.) had stronger antitumor activities and higher chemotherapeutic ratio than mitomycin C against such murine ascitic tumors as P388 and L1210 leukemia, B16 melanoma, M5076 reticulum cell sarcoma of ovarian origin, Colon 26 carcinoma, Ehrlich carcinoma, and MH134 hepatoma. In tests against murine and human solid tumors implanted s.c. in normal mice and nude mice, respectively, FK973 (i.v.) inhibited growth of murine tumors (M5076 sarcoma, Colon 38 carcinoma, B16 melanoma, and Lewis lung carcinoma) by 66-100% and human tumors (LX-1 lung, MX-1 mammary, and SC-6 stomach carcinoma) by 84-99%. In studies with drug-resistant P388 leukemia, FK973 was also effective against vincristine-resistant P388, moderately effective against mitomycin C (MMC)- and adriamycin-resistant P388, and partially effective against cyclophosphamide-resistant P388 cells in mice. Leukopenic effects of FK973 and MMC in mice were comparable at doses which gave antitumor activity almost equally. FK973 had no effect on the numbers of platelets and red blood cells, whereas MMC markedly decreased both. FK973 decreased the numbers of colony forming units in spleen and in culture and the effect was less than that of MMC. Therefore, FK973 may give weaker myelosuppression than MMC. The results suggest that FK973 will be a beneficial drug for the treatment of cancer.
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PMID:Antitumor activity and hematotoxicity of a new, substituted dihydrobenzoxazine, FK973, in mice. 334 97


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