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 present study provides evidence that green tea extract (GTE), consisting of polyphenol components, is a highly active nucleoside transport inhibitor. GTE markedly inhibited radiolabeled thymidine and uridine transport in mouse leukemia L1210 cells, with IC50 values of 3.2 and 8.0 mumol/L, respectively. GTE blocked the rescue effect of exogenous nucleosides and enhanced the cytotoxicity of AraC and MTX to L1210 cells and human hepatoma BEL-7402 cells. GTE markedly potentiated the inhibitory effect of AraC on leukemia L1210 and P388 in mice. These results indicate that GTE is potentially useful when combined with antimetabolites in cancer chemotherapy.
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PMID:Green tea extract inhibits nucleoside transport and potentiates the antitumor effect of antimetabolites. 178 98

Arterial infusion chemotherapy is commonly-used modality for controlling cancers located in specific regions. Previously we described a new method of intra-hepatic arterial catheterization through the left subclavian artery using a subcutaneously-implanted silicone reservoir. In the present paper, we report our experience using a low dose-intermittent intraarterial (i.a.) infusion chemotherapy. Since February, 1982, 70 patients including 44 cases of metastatic liver cancer, 16 cases of primary hepatocellular carcinoma and 10 cases of other gastrointestinal malignancies, have been treated with this low dose-intermittent i.a. infusion chemotherapy, the drugs used being as follows. 1) MMC 4 mg, 5-FU 500 mg, AraC 40 mg/2w, 2) MMC 4 mg/w, 3) 5-FU 500 mg/w, MMC 4 mg/2w, ADM 30 mg/4w. Here, we briefly review the effectiveness of this modality for controlling regional diseases including liver metastases. The average hospital-free interval was 156 days and partial responses were observed in 43% (21/49) of cases. Side effects during the therapy were only mild bone marrow suppression and anorexia, which were tolerable in out-hospital care. We also studied the pharmacokinetics of i.a. infusion into the liver in comparison with i.v. infusion using 99mTc-RBC, and found that the ratio of i.a. to i.v. with regard to trans-arterial drug delivery to the liver was 10.0. From the viewpoints of first pass effect and increased local concentration theory, this ratio suggests that the effectiveness of a low-dose anti-tumor agent administered intraarterially is not so low. Accordingly, we believe that low dose-intermittent i.a. infusion chemotherapy is beneficial as an induction and maintenance chemotherapy for patients with regionally located cancers because it is effective, safer and prolongs the hospital-free interval.
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PMID:[Low-dose intermittent intra-arterial infusion chemotherapy]. 299 38

Microcystins are naturally occurring hepatotoxins produced by strains of Microcystis aeruginosa. They are involved in promoting primary liver tumours and a previous study showed that they might also be tumour initiators. In this study we demonstrate that microcystin-LR (MCLR) at doses that were not cytotoxic (0.01-1 microg/ml), induced dose and time dependent DNA strand breaks in human hepatoma cell line HepG2. These DNA strand breaks were transient, reaching a maximum level after 4h of exposure and declining with further exposure. In the presence of the DNA repair inhibitors cytosine arabinoside (AraC) and hydroxyurea (HU), together with MCLR, DNA strand breaks accumulated after prolonged exposure. These results suggest that DNA strand breaks are intermediates, produced during the cellular repair of MCLR induced DNA damage. Digestion of DNA with purified, oxidative DNA damage specific enyzmes, endonuclease III (Endo III) and formamidopyrimidine-DNA glycosylase (Fpg) markedly increased DNA strand breaks in MCLR treated cells, providing evidence that a substantial portion of the MCLR induced DNA strand breaks originate from excision of oxidative DNA adducts. A hydroxyl radical scavenger (DMSO) significantly reduced MCLR induced DNA damage. From these results we conclude that MCLR induces formation of reactive oxygen species that cause DNA damage, and that MCLR may act as an initiator of liver cancer.
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PMID:Microcystin-LR induces oxidative DNA damage in human hepatoma cell line HepG2. 1246 60

Increasing evidence indicates that broadly neutralizing antibodies (bNAbs) play an important role in immune-mediated control of hepatitis C virus (HCV) infection, but the relative contribution of neutralizing antibodies targeting antigenic sites across the HCV envelope (E1 and E2) proteins is unclear. Here, we isolated thirteen E1E2-specific monoclonal antibodies (MAbs) from B cells of a single HCV-infected individual who cleared one genotype 1a infection and then became persistently infected with a second genotype 1a strain. These MAbs bound six distinct discontinuous antigenic sites on the E1 protein, the E2 protein, or the E1E2 heterodimer. Three antigenic sites, designated AS108, AS112 (an N-terminal E1 site), and AS146, were distinct from previously described antigenic regions (ARs) 1 to 5 and E1 sites. Antibodies targeting four sites (AR3, AR4-5, AS108, and AS146) were broadly neutralizing. These MAbs also displayed distinct patterns of relative neutralizing potency (i.e., neutralization profiles) across a panel of diverse HCV strains, which led to complementary neutralizing breadth when they were tested in combination. Overall, this study demonstrates that HCV bNAb epitopes are not restricted to previously described antigenic sites, expanding the number of sites that could be targeted for vaccine development.IMPORTANCE Worldwide, more than 70 million people are infected with hepatitis C virus (HCV), which is a leading cause of hepatocellular carcinoma and liver transplantation. Despite the development of potent direct acting antivirals (DAAs) for HCV treatment, a vaccine is urgently needed due to the high cost of treatment and the possibility of reinfection after cure. Induction of multiple broadly neutralizing antibodies (bNAbs) that target distinct epitopes on the HCV envelope proteins is one approach to vaccine development. However, antigenic sites targeted by bNAbs in individuals with spontaneous control of HCV have not been fully defined. In this study, we characterize 13 monoclonal antibodies (MAbs) from a single person who cleared an HCV infection without treatment, and we identify 3 new sites targeted by neutralizing antibodies. The sites targeted by these MAbs could inform HCV vaccine development.
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PMID:Broadly Neutralizing Antibodies Targeting New Sites of Vulnerability in Hepatitis C Virus E1E2. 3106 27