Hepatic arterial infusion chemotherapy using high-dose 5-fluorouracil and cisplatin with or without interferon-alpha for the treatment of advanced hepatocellular carcinoma with portal vein tumor thrombosis.

OBJECTIVE: In this retrospective study, we assessed the efficacy of hepatic arterial infusion chemotherapy (HAIC) using high-dose 5-fluorouracil (5-FU) and cisplatin with or without interferon (IFN)-alpha for the treatment of advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis. MATERIAL AND METHODS: Fifty-two patients were included in the analysis. The patients were treated with 5-FU (750 mg/m(2)) and cisplatin (25 mg/m(2)) from Days 1 to 4. IFN-alpha was administered subcutaneously at a dose of 3 million units from Days 1 to 4, and then every other day for 24 days. Chemotherapy was repeated every 4 weeks. Thirty-one patients were treated with 5-FU, cisplatin and IFN-alpha (FPI group) and 21 were treated with 5-FU and cisplatin (FP group). RESULTS: An objective tumor response was achieved in six patients (19.4%) in the FPI group. In the FP group, 12 patients (57.1%) achieved an objective tumor response (p = 0.015). The cumulative survival rate was higher in the FP group than the FPI group, but this difference was not statistically significant (p = 0.353). The median survival time for the 18 responders was 14 months (range 4-25 months), and their 6, 12, and 24-month cumulative survival rates were 89%, 83%, and 25%, respectively. CONCLUSIONS: HAIC using high-dose 5-FU plus cisplatin achieved a good tumor response. Adding IFN-alpha did not show any additional beneficial effects in terms of tumor response rate or survival.

A primate-specific, brain isoform of KCNH2 affects cortical physiology, cognition, neuronal repolarization and risk of schizophrenia.

Organized neuronal firing is crucial for cortical processing and is disrupted in schizophrenia. Using rapid amplification of 5' complementary DNA ends in human brain, we identified a primate-specific isoform (3.1) of the ether-a-go-go-related K(+) channel KCNH2 that modulates neuronal firing. KCNH2-3.1 messenger RNA levels are comparable to full-length KCNH2 (1A) levels in brain but three orders of magnitude lower in heart. In hippocampus from individuals with schizophrenia, KCNH2-3.1 expression is 2.5-fold greater than KCNH2-1A expression. A meta-analysis of five clinical data sets (367 families, 1,158 unrelated cases and 1,704 controls) shows association of single nucleotide polymorphisms in KCNH2 with schizophrenia. Risk-associated alleles predict lower intelligence quotient scores and speed of cognitive processing, altered memory-linked functional magnetic resonance imaging signals and increased KCNH2-3.1 mRNA levels in postmortem hippocampus. KCNH2-3.1 lacks a domain that is crucial for slow channel deactivation. Overexpression of KCNH2-3.1 in primary cortical neurons induces a rapidly deactivating K(+) current and a high-frequency, nonadapting firing pattern. These results identify a previously undescribed KCNH2 channel isoform involved in cortical physiology, cognition and psychosis, providing a potential new therapeutic drug target.