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)

We present herein the novel technique for constructing inverted cell-adhesion patternes on PEG gel modified glass surfaces by photoirradiation using the same photomask and materials. The PEG gel micropatterns were prepared by a photolithographic technique using a photomask with 100 microm aligned cavities after spin-coating of a mixed solution of alpha,omega-dimethacryloyl-PEG (PEG-DMA) and a photoinitiator on glass surfaces. When methanol was used as a casting solvent for the spin-coating (Method A), the circular PEG gel domains with a diameter of 100 microm were fabricated on the surface, and as would be predicted, seeded bovine aortic endothelial cells (BAECs) adhered to the glass area on the constructed surface to form a BAECs sheet with 100 microm aligned cavity. In contrast, it was rather surprising for us that a complete inverted cell pattern was formed when the PEG gel pattern surface was prepared using methanol/water co-solvent (Method B). Furthermore, when hepatoma cancer cells were seeded on the constructed surface prepared by Method B, they formed a spherical multicellular aggregate (spheroid) on the unmodified PEG gel domains without feeder cells. In order to obtain information on this peculiar phenomenon, fluorescence-based protein adsorption experiments, contact angle measurements, and X-ray photospectroscopy (XPS) analysis were carried out.
 ...
PMID:Inverted pattern formation of cell microarrays on poly(ethylene glycol) (PEG) gel patterned surface and construction of hepatocyte spheroids on unmodified PEG gel microdomains. 1937 Feb 50

Hepatitis C virus (HCV) develops persistent infection in most infected patients, and eventually cause chronic hepatitis, liver cirrhosis and then hepatocellular carcinoma. The combination therapy of PEG-IFN and ribavirin improves the efficacy in many patients, while it does not lead to sufficient achievements in genotype1b patients. To invent new anti-HCV reagent, we focused on host factors which HCV take advantage of in its life-cycle. We identified serine palmitoyltransferase inhibitor as anti-HCV reagent through high-through put screenig using HCV replicon cells. Moreover, we evaluate the anti-HCV effect of SPT-inhibitor in vivo with humanized chimeric mice. SPT-inhibitor led to rapid decline in serum HCV-RNA of about 1-2log within 8 day, futhermore the combination therapy of SPT-inhibitor and PEG-IFN achieved about 3log reduction in serum HCV-RNA. At last, we investigated the mechanism of anti-HCV effect of SPT-inhibitor. It has been reported that sphingolipids and cholesterol compose the lipid raft, in which the replication of HCV occur. We investigated the influence of SPT-inhibitor to lipid rafts by analysing the detergent resistant membrane (DRM). The analysis proved that SPT inhibitor got HCV RNA dependent RNA polymerase (NS5B) to move to detergent soluble fraction from DRM, and Biacore analysis indicated the binding of sphingomyelin to NS5B. These results suggested SPT inhibitor got NS5B to release from replication complex.
 ...
PMID:[Suppression of hepatitis C virus with the reagent targetting host factors]. 1937 99

Hepatitis C Virus (HCV) infection is the major cause of chronic liver disease, leading to cirrhosis and hepatocellular carcinoma, which affects more than 200 million people worldwide. Currently the only therapeutic regimens are subcutaneous interferon-alpha or PEG-interferon alone or in combination with oral ribavirin. Although combination therapy is reasonably successful with the majority of genotypes, its efficacy against the predominant genotype (genotype 1) is moderate at best, with only approximately 50% of the patients showing sustained virological response. We recently disclosed the discovery of Boceprevir, SCH 503034 (1), which is a novel, potent, selective, orally bioavailable NS3 protease inhibitor that has been shown to be efficacious in humans and is currently undergoing clinical trials. As second generation compounds, we have further explored various novel structures with the aim of improving enzyme and cellular binding activities of 1. Herein, we disclose our efforts toward the identification of a novel P(3) sulfonamide-capped inhibitor that demonstrated improved binding and cellular activity compared to 1. X-ray structure of one of these inhibitors bound to the enzyme revealed a hydrogen bond of the P(3) sulfonamide group to Cys-159 which resulted in improved binding and cellular potency.
 ...
PMID:Discovery of novel P3 sulfonamide-capped inhibitors of HCV NS3 protease. Inhibitors with improved cellular potencies. 1948 46

Modular, bioactive, macroporous scaffolds were formed by crosslinking poly(ethylene glycol) (PEG) microspheres around living cells. Hydrogel microspheres were produced from reactive PEG derivatives in aqueous sodium sulfate solutions without the use of surfactants or copolymers. Microspheres were formed following thermally induced phase separation if the gel point was reached prior to extensive coarsening of the PEG-rich domains. Three types of PEG microspheres with different functionalities were used to form scaffolds: one type provided mechanical support, the second type provided controlled delivery of the angiogenesis-promoting molecule, sphingosine 1-phosphate (S1P) and the third type served as a slowly dissolving non-cytotoxic porogen. Scaffolds were formed by centrifuging microspheres in the presence of HepG2 hepatoma cells, resulting in a homogenous distribution of cells. During overnight incubation at 37 degrees C, the microspheres reacted with serum proteins in cell culture medium to stabilize the scaffolds. Within 2 days in culture, macropores formed due to the dissolution of the porogenic PEG microspheres, without affecting cell viability. Gradients in porosity were produced by varying the buoyancy of the porogenic microspheres. Conjugated RGD cell adhesion peptides and the delivery of S1P promoted endothelial cell infiltration through macropores in the scaffolds. The scaffolds presented here differ from previous hydrogel scaffolds in that: (i) cells are not encapsulated in hydrogel; (ii) macropores form in the presence of cells; and (iii) scaffold properties are controlled by the modular assembly of different microspheres that perform distinct functions.
 ...
PMID:Modular scaffolds assembled around living cells using poly(ethylene glycol) microspheres with macroporation via a non-cytotoxic porogen. 1960 45

Hepatitis C virus (HCV) infection remains a large-scale and significant health concern. The combination of subcutaneously administered pegylated interferon and oral ribavirin is the FDA-approved regimen for the treatment of chronic HCV infection. Combination therapy may result in a sustained virologic response leading to HCV eradication, with a reduction in risk for cirrhosis, hepatic decompensation, and hepatocellular carcinoma. However, the combination of PEG-IFN and ribavirin does not universally result in cure in all patients who undergo treatment. In this article, the authors discuss immunomodulatory therapies and clinical trials in the treatment of HCV infection.
 ...
PMID:Hepatitis C virus infection and immunomodulatory therapies. 1962 56

TMC-435, being developed by Tibotec Pharmaceuticals Ltd, is an orally administered, macrocyclic inhibitor of the HCV NS3/4A serine protease. HCV infection can cause chronic hepatitis, cirrhosis of the liver and hepatocellular carcinoma. The HCV NS3/4A enzyme is an essential component for viral replication, suggesting that this protein is a key therapeutic target. Biochemical assays demonstrated potent inhibition of HCV NS3/4A by TMC-435 in all HCV genotypes tested, with the exception of HCV-3. In cellular replicon models, the compound selectively inhibited HCV-1 replication and displayed additive effects with ribavirin, and had synergistic activity with IFNalpha and an NS5B polymerase inhibitor. Pharmacokinetic data demonstrated high exposure and good oral bioavailability, supporting once-daily dosing of TMC-435 in humans. In phase I and II clinical trials, the administration of TCM-435 to patients infected with HCV-1, alone or in combination with PEG-IFNalpha and ribavirin, produced significant reductions in HCV-RNA without any significant adverse effects, thus providing a basis for further development of this compound as an anti-HCV therapeutic agent. At the time of publication, phase II trials with TMC-435 were ongoing.
 ...
PMID:TMC-435, an NS3/4A protease inhibitor for the treatment of HCV infection. 1964 31

A57 -year-old man. Though chronic hepatitis C was pointed out before, it had been left untreated for about 5 years. He was hospitalized because many venereal diseases had been pointed out in the liver by abdomen ultrasonography. Results of close examination revealed stage IV B with bone metastases, and pulmonary metastases was diagnosed. After consultation, whole-body chemotherapy combining S-1 and PEG-IFN was attempted as of June 26, 2007. S-1 (80 mg/day) was then administered every day for two weeks with drug withdrawal for one week. PEG-IFNalpha-2a (180 microg)was administered once a week. We set three weeks as one course. The liver tumor was markedly reduced, and the pulmonary metastases were also reduced at the completion of 5 courses. The therapeutic effectiveness of this chemotherapy was confirmed by imaging test. The course was favorable, and whole-body chemotherapy was discontinued on January 29, 2008. At this writing in October of 2008, the course has been uneventful. This treatment method is a promising choice for whole-body chemotherapy for advanced hepatocarcinoma in the future. We have added some review of the literature, and the S-1+PEG-IFN combination chemotherapy is reported.
 ...
PMID:[A case of advanced hepatocarcinoma responding to combination therapy of S-1 and PEG-IFN]. 1983 44

Aberrant squamous cell carcinoma antigen (SCCA) expression is an early event in hepatocarcinogenesis, and increasing serum levels of SCCA variants IgM immune complexes (SCCA-IgM IC) have been found in cirrhotic patients developing hepatocellular carcinoma (HCC). We longitudinally evaluated a cohort of cirrhotic patients with hepatitis C virus infection (HCV) who underwent pegylated interferon (PEG-IFN) and ribavirin treatment. SCCA-IgM IC levels were assessed in the sera of 33 cirrhotic patients with HCV (21 males, median age 57 years) before, at the end and at 6-month and 1-year follow-up after treatment with PEG-IFN and ribavirin. SCCA-IgM IC serum levels (arbitrary units/mL, AU/mL) were evaluated according to treatment outcome: sustained virological response (SVR) vs nonresponse (NR). Overall, 15 patients obtained a SVR to antiviral therapy (45%). There was no significant difference in baseline SCCA-IgM IC serum levels between SVR and NR patients. When compared to baseline (451.2 AU/mL), SVR patients showed a significant decrease in median SCCA-IgM IC serum levels at the end of treatment (186.8 AU/mL, P = 0.013) and at both 6-month (96.8 AU/mL, P < 0.001) and 1-year follow-up (52.4 AU/mL, P < 0.001), while no significant modification was observed in NR patients. In patients with HCV-related liver cirrhosis, successful antiviral therapy is associated with a dramatic and significant decrease in SCCA-IC serum levels. Because of the pathophysiological correlation between SCCA and liver carcinogenesis, it is hypothesized that in patients with liver cirrhosis, SVR may be accompanied by a decreased proliferative stimulation.
 ...
PMID:Successful antiviral therapy determines a significant decrease in squamous cell carcinoma antigen-associated (SCCA) variants' serum levels in anti-HCV positive cirrhotic patients. 1984 Mar 64

Human hepatocellular carcinoma (HCC) is one of the most causes of cancer-related death and is well known because of resistant to chemotherapeutic drug. Co-delivery of antitumor agent docetaxel and iSur-pDNA, a suppressor of metastatic and resistance-related protein survivin, was postulated to achieve synergistic/combined effect of antitumor drug and gene therapeutics. To valid this hypothesis, a folate-modified multifunctional nanoassembly (FNA) loading both docetaxel and iSur-pDNA was constructed and evaluated as a therapeutic approach for HCC. The FNAs were prepared with folate-modified lipid FA-PEG-DSPE as the target to tumor, protamine sulfate (PS) as the condenser to protect and enhance the nuclear transfer of iSur-pDNA, and DOPE-based lipid envelope as the carrier of doctaxel and PS/DNA complex to achieve their co-delivery and enhance internalization into hepatoma cells. FNAs showed the particle size about 200nm with encapsulation efficiency >90%. Blank nanoassemblies (BNAs) loading only reporter gene revealed higher transfection efficiency with neglectable cytotoxicity compared with Lipofectamine 2000, which could result from enhanced cellular uptake via ligand-receptor recognition and efficient nuclear delivery mediated by PS. Cytotoxicity of FNAs against hepatocellular carcinoma cell line BEL 7402 was much higher than either docetaxel or non-docetaxel FNAs (nFNAs) loading only iSur-pDNA, and was also superior to the combined treatment with free docetaxel and nFNAs. Better antitumor efficacy of FNAs with low systemic toxicity was also observed on mouse hepatocellular carcinoma xenograft model. These results suggested that co-delivery of docetaxel and iSur-pDNA with FNAs could be a safer and more efficient strategy for the treatment of locally advanced and metastatic HCC.
 ...
PMID:The characteristics and performance of a multifunctional nanoassembly system for the co-delivery of docetaxel and iSur-pDNA in a mouse hepatocellular carcinoma model. 1984 17

Hepatitis D is caused by infection with the hepatitis D virus (HDV) and is considered to be the most severe form of viral hepatitis in humans. Hepatitis D occurs only in individuals positive for the HBV surface antigen (HBsAg) as HDV is a defective RNA viroid that requires HBsAg for transmission. At least eight different HDV genotypes have been described and each has a characteristic geographic distribution and a distinct clinical course. HDV and HBV coinfection can be associated with complex and dynamic viral dominance patterns. Chronic HDV infection leads to more severe liver disease than HBV monoinfection and is associated with accelerated fibrosis progression, earlier hepatic decompensation and an increased risk for the development of hepatocellular carcinoma. So far, only IFN-alpha treatment has proven antiviral activity against HDV in humans and has been linked to improved long-term outcomes. Studies conducted in the past 2 years on the use of PEG-IFN-alpha show that a sustained virologic response to therapy, measured in terms of undetectable serum HDV RNA levels, can be achieved in about one quarter of patients with hepatitis D. Novel alternative treatment options including prenylation inhibitors are awaiting clinical development for use in hepatitis D.
 ...
PMID:Epidemiology, pathogenesis and management of hepatitis D: update and challenges ahead. 2005 70


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>