Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human glypican 3 (GPC3) is preferentially expressed in the tumor tissues of liver cancer patients. In this study, we obtained a monoclonal antibody (mAb) against the COOH-terminal part of GPC3, which induced antibody-dependent cellular cytotoxicity (ADCC). The mAb, designated GC33, exhibited marked tumor growth inhibition of s.c. transplanted Hep G2 and HuH-7 xenografts that expressed GPC3 but did not inhibit growth of the SK-HEP-1 that was negative for GPC3. GC33 was efficacious even in an orthotopic model; it markedly reduced the blood alpha-fetoprotein levels of mice intrahepatically transplanted with Hep G2 cells. Humanized GC33 (hGC33) was as efficacious as GC33 against the Hep G2 xenograft, but hGC33 lacking carbohydrate moieties caused neither ADCC nor tumor growth inhibition. Depletion of CD56+ cells from human peripheral blood mononuclear cells markedly abrogated the ADCC caused by hGC33. The results show that the antitumor activity of hGC33 is mainly attributable to ADCC, and in human, natural killer cell-mediated ADCC is one possible mechanism of the antitumor effects by GC33. hGC33 will provide a novel treatment option for liver cancer patients with GPC3-positive tumors.
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PMID:Anti-glypican 3 antibody as a potential antitumor agent for human liver cancer. 1904 63

Type 2-diabetic (T2D) disease has been reported to increase the incidence of liver cancer, however, the underlying pathophysiology is still not fully understood. Here, we aimed to reveal the underlying pathophysiology association between the T2D and hepatocellular carcinoma (HCC) and, therefore, to find the possible therapeutic targets in the occurrence and development of HCC. The methylation microarray data of T2D and HCC were extracted from the Gene Expression Omnibus and The Cancer Genome Atlas. A total of 504 differentially methylated genes (DMGs) between T2D samples and the controls were identified, whereas 6269 DMGs were identified between HCC samples and the control groups. There were 336 DMGs coexisting in diabetes and HCC, among which 86 genes were comethylated genes. These genes were mostly enriched in pathways as glycosaminoglycan biosynthesis, fatty acid, and metabolic pathway as glycosaminoglycan degradation and thiamine, fructose and mannose. There were 250 DMGs that had differential methylation direction between T2D DMGs and HCC DMGs, and these genes were enriched in the Sphingolipid metabolism pathway and immune pathways through natural killer cell-mediated cytotoxicity and ak-STAT signaling pathway. Eight genes were found related to the occurrence and development of diabetes and HCC. Moreover, the result of protein-protein interaction network showed that CDKN1A gene was related to the prognosis of HCC. In summary, eight genes were found to be associated with the development of HCC and CDKN1A may serve as the potential prognostic gene for HCC.
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PMID:The underlying pathophysiology association between the Type 2-diabetic and hepatocellular carcinoma. 3058 32

Hepatocellular carcinoma (HCC) is a world-wide health problem. Poor and delayed diagnoses as well as high recurrence rate resulting in high mortality rate. In this study, we established a patient-derived xenograft (PDX) model from HCC patient, and continuously maintained with subcutaneous passage more than 20 times. This HCC PDX tumor exhibited the same histological characteristics with the HCC patient and could be used to verify therapeutic effect of liver cancer. We further evaluated this PDX model by experimental chemotherapy, demonstrating that this HCC PDX model was sensitive to sorafenib treatment. Further, the potential of natural killer cell-based immunotherapy for HCC was tested using this model. We found that NK92 cells effectively suppressed the tumor growth in vivo and prolonged the survival time of HCC-bearing PDX mice. This study indicates that HCC PDX model is a good platform to testify the efficacy of preclinical chemotherapy and immunotherapy.
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PMID:Establishment and Preclinical Therapy of Patient-derived Hepatocellular Carcinoma Xenograft Model. 3233 45

Liver cancer is a particularly aggressive group of malignancies with historically low survival rates. Despite advancements in cancer treatments in general in the last few decades, incidence and mortality have not changed. Even though some phase 1 and 2 studies have shown promising results, many medication have failed to reach a sustainable level of efficacy to move into the clinical setting. Immunotherapy drugs have shown impressive results in the treatment of specific immunogenic cancers, prompting the possibility of their use in liver cancers. Immunotherapy medications approved for other cancers have received FDA accelerated approval for treatment of hepatocellular carcinoma. But, these approvals are contingent upon verification and description of clinical benefit in confirmatory trials. With more treatments in development involving cancer vaccines and natural killer cell-mediated therapy, liver cancer treatment is being reinvigorated with a broad array of new treatment angles. In this review article, we discuss these treatments, focusing on mechanism of action and clinical trials. Much needed advancements in treating late- and early-stage liver cancers will require new and innovative immunotherapeutic treatments.
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PMID:Current Perspectives in Immunotherapy for Liver Cancer. 3286 9