S-1 for treatment of advanced hepatocellular carcinoma: a systematic review of the literature.

Hepatocellular carcinoma (HCC) is the most common liver neoplasm worldwide. Based on its potent inhibition of dihydropyrimidine dehydrogenase (DPD), S-1 is expected to be more active than other fluoropyrimidines against HCC with DPD activity. This systematic review was aimed to assess the efficacy and safety of S-1 for treatment of advanced HCC. PubMed, the Cochrane Library, EMBA-SE, and ClinicalTrials.gov were searched using the terms "Hepatocellular Carcinoma" or "HCC" or "Hepatoma" or "Liver cancer" and ''S-1''. Outcomes of main interest included overall survival (OS) and toxicities. We identified four studies of S-1 treatment alone from 1059 references, including a total of 272 patients. There were two original articles and two conference abstracts. The percentage of male patients ranged from 88 to 91.3% and median age ranged from 59 to 70 years. Median OS ranged from 8.6 to 16.5 months. The incidences of toxicity of more than 50% were thrombocytopaenia and fatigue. According to the original description, toxicities were acceptable. The current evidence from the available clinical studies suggests that S-1 may be an effective and tolerable treatment for advanced HCC. Further clinical studies are warranted to further investigate this treatment option.

Transcatheter arterial chemoembolisation (TACE) plus S-1 for the treatment of BCLC stage B hepatocellular carcinoma refractory to TACE.

AIM OF THE STUDY: To assess the efficacy and safety of transcatheter arterial chemoembolization (TACE) plus S-1 for the treatment of Barcelona Clinic Liver Cancer (BCLC) Stage B HCC refractory to TACE. MATERIAL AND METHODS: 26 patients meeting the eligibility criteria were enrolled. TACE was given on day 1, and S-1 on days 2-15. Tumor assessment was performed one month later according to mRECIST. The primary endpoints were TTP and OS. RESULTS: Twenty-six patients received 176 TACE interventions in all. Fifteen patients of TACE plus S-1 received a total of 55 cycles of treatment of S-1, with a median of 4 cycles (range, 2-6). The total dose of S-1 was 6165 mg per day, while average was 120 mg (range, 100-125 mg) for 15 patients of TACE plus S-1. Median TTP and OS of TACE plus S-1 were 6 months (95% CI: 4.7-7.3) and 18 months (95% CI: 15.3-24.7), respectively, while TACE monotherapy was 4 months (95% CI: 2.4-5.6) and 13 months (95% CI: 9.8-16.2), respectively, and significant differences were detected. Though there were higher DCRs in patients of TACE plus S-1, no significant differences were detected. A total of 612 adverse events occurred during the course of the treatment, 367 in TACE plus S-1 and 245 in TACE mono-therapy. There were significant differences to anorexia and nausea, but they were tolerable. CONCLUSIONS: TACE plus S-1 in the present analysis was tolerable and associated with an interesting TTP and OS. TACE plus S-1 may be used as a new treatment method to BCLC Stage B HCC refractory to TACE.

Exosomal LINC00161 promotes angiogenesis and metastasis via regulating miR-590-3p/ROCK axis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a lethal malignancy with few effective options for therapeutic treatment in its advanced stages. While exosomal LINC00161 has been identified as a potential biomarker for HCC, its regulatory function and clinical values remain largely unknown. LINC00161 expressions in serum-derived exosomes from HCC patients and HCC cells were determined by qRT-PCR. The ability of proliferation, migration, and angiogenesis in HUVECs was assessed by MTT, Transwell, and tube formation. Luciferase reporter assay and AGO2-RIP assay were conducted to explore the interactions among LINC00161, miR-590-3p, and ROCK2. The level of ROCK signal-related proteins was examined by Western blotting and immunohistochemistry (IHC) assay. Subcutaneous tumor growth was observed in nude mice, in which in vivo metastasis was observed following tail vein injection of HCC cells. High levels of LINC00161 were detected in both serum-derived exosomes from HCC patients and the supernatants of HCC cell lines and were significantly associated with poor survival. Functional study demonstrated that exosomal LINC00161 derived from HCC-cells were significantly associated with enhanced proliferation, migration, and angiogenesis in HUVECs in vitro, all of which were effectively inhibited when LINC00161 was sliced with shRNA in HCC-cells. In vivo experiment showed that LINC00161 loss inhibited tumorigenesis and metastasis of HCC. Mechanistic study revealed that exosome-carried LINC00161 directly targeted miR-590-3p and induced its downstream target ROCK2, finally activating growth/metastasis-related signals in HCC. Exosome-carried LINC00161 promotes HCC tumorigenesis through inhibiting miR-590-3p to activate the ROCK2 signaling pathway, suggesting that LINC00161 may be used as potential targets to improve HCC treatment efficiency.

Prevalence of the methylenetetrahydrofolate reductase 677C>T polymorphism in the pregnant women of Yunnan Province, China.

Mutations in the methylenetetrahydrofolate reductase (MTHFR) gene can result in a reduced ability to utilize folic acid. The MTHFR 677C>T polymorphism in particular has been linked to both birth defects and pregnancy-associated diseases. This study aimed to evaluate the prevalence of the MTHFR 677C>T mutation among pregnant women in Yunnan Province so as to collect baseline data that may be utilized to guide folic acid supplementation efforts and to support related disease prevention programs. We retrospectively reviewed 3387 pregnant women from Yunnan Province. The MTHFR 677C>T polymorphism was identified using polymerase chain reaction (PCR) and DNA sequencing. In total, 1350 (39.9%) subjects were homozygous for the C allele (CC), 1540 (45.4%) subjects were heterozygous (CT), and 497 (14.7%) subjects were homozygous for the T allele (TT). The MTHFR 677C>T polymorphism was found to be present within the studied population, with ∼60% of these patients being either heterozygous or homozygous for the mutant allele and with an overall T allele frequency of 0.37. The frequency of the T allele was significantly higher among pregnant women with complications relative to women with healthy pregnancies, particularly among women <30 years old. As such, the maternal MTHFR 677C>T polymorphism may be a genetic risk factor associated with pregnancy complications and may help identify pregnant women at a high risk of such complications.

[Photo-catalytic degradation of gas phase benzene and toluene over multi-composite TiO2 catalyst].

Photo-catalytic degradation of gas-phase benzene and toluene were studied in the condition of no catalyst, pure anatase catalyst, pure rutile catalyst and multi-composite catalyst. The influences of initial concentration of reactants and the catalysts of different composite on photo-catalytic degradation rate of gas-phase benzene and toluene were investigated. The results show that the degradation efficiency of benzene and toluene is improved a lot on anatase catalyst, but improved a little on rutile catalyst in relation to the crystal-structure of anatase and rutile catalyst. In the condition of no catalyst and pure rutile catalyst, toluene is easier to be degradated than benzene, and on anatase catalyst benzene is easier to be done than toluene. The initial concentration of reactant has an effect on the photo-catalytic degradation process. The degradation rates of benzene and toluene are faster in low concentration than in high concentration. A certain amount of rutile doped in anatase catalyst could improve the photo-catalytic activity. The catalyst with 80% anatase and 20% rutile shows the best photo-catalytic activity to benzene, and the catalyst with 90% anatase and 10% rutile gives the best photo-catalytic activity to toluene.

[Characteristics of atmospheric ozone in the urban area of Ji'nan].

Based on the observational data of near surface O3 in the urban area of Ji'nan during the latest two years, the O3 concentrations and their temporal variation characteristics were analyzed. The results showed that O3 concentrations fluctuated periodically,and the photochemical pollution in Ji'nan was serious. Diurnal variations of ozone concentrations exhibited with the characteristic of a single peak, and showed the maximum in the afternoon and minimum in the early morning before sunrise. Ozone concentrations in spring and summer were higher than autumn and winter, while the varying scopes of ozone concentrations in summer and autumn were broader than spring and winter. Variations of ozone concentrations in weekend days were different from weekdays, which caused by the temporal regulation of human activities.