Impact of Hepatitis Virus on the Feasibility and Efficacy of Anticancer Agents in Patients With Hepatocellular Carcinoma in Phase I Clinical Trials

This study was approved by the NCCH institutional review board and performed in compliance with our institutional guidelines. Patients positive for anti-HCV antibody or HBV antigen (HBsAg) were considered to have HCC due to chronic viral hepatitis, whereas those without anti-HCV antibody nor HBsAg were considered to have HCC by another etiology (non-B/non-C). All medical records were reviewed to summarize the patients' clinical characteristics, treatments, and outcomes based on the status of chronic viral hepatitis. The baseline clinical characteristics included age, gender, ECOG-performance status (PS), treatment history, spread from the primary site, number of metastatic sites and their locations, laboratory tests, and the C-P classification. The outcomes consisted of the date of P-I enrolment and progression, the date of death or loss to follow-up, the best response to therapy based on Response Evaluation Criteria in Solid Tumors (RECIST), and adverse events based on Common Terminology Criteria for Adverse Events (CTCAE) ver.4. Endpoints and Statistical Methods The primary outcome of interest was the effect of chronic viral hepatitis on the efficacy and feasibility of the drugs on patients with HCC who enrolled in P-Is. We assessed the effectiveness through time to failure (TTF), OS, and the best response, and the feasibility through toxicity. TTF was defined as the time from the start of P-I enrolment to discontinuation (as judged by the P-I investigators), b...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research

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Cytosolic arginine sensor for mTORC1 subunits 1 and 2 (CASTOR1 and CASTOR2) inhibit the mammalian target of rapamycin complex 1 (mTORC1) upon arginine deprivation. mTORC1 regulates cell proliferation, survival, and metabolism and is often dysregulated in cancers, indicating that cancer cells may regulate CASTOR1 and CASTOR2 to control mTORC1 signaling and promote tumorigenesis. mTORC1 is the most effective therapeutic target of Kaposi sarcoma, which is caused by infection with the Kaposi sarcoma–associated herpesvirus (KSHV). Hence, KSHV-induced cellular transformation is a suitable model for investigating mTORC1 reg...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
The presence of tumor-infiltrating T cells is associated with favorable patient outcomes, yet most pancreatic cancers are immunologically silent and resistant to currently available immunotherapies. Here we show using a syngeneic orthotopic implantation model of pancreatic cancer that Pik3ca regulates tumor immunogenicity. Genetic silencing of Pik3ca in KrasG12D/Trp53R172H-driven pancreatic tumors resulted in infiltration of T cells, complete tumor regression, and 100% survival of immunocompetent host mice. By contrast, Pik3ca-null tumors implanted in T cell–deficient mice progressed and killed all of the animals. Ad...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
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Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
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Source: Colloids and Surfaces A: Physicochemical and Engineering Aspects - Category: Chemistry Source Type: research
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Source: Chinese Chemical Letters - Category: Chemistry Source Type: research
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Source: Genetics and Molecular Biology - Category: Genetics & Stem Cells Source Type: research
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Source: Genetics and Molecular Biology - Category: Genetics & Stem Cells Source Type: research
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Source: Genetics and Molecular Biology - Category: Genetics & Stem Cells Source Type: research
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