Evaluation of hazardous airborne carbonyls in five urban roadside dwellings: A comprehensive indoor air assessment in Sri Lanka

Indoor hazardous airborne carbonyls were quantified in five natural-ventilated roadside dwellings in Colombo, Sri Lanka. The total concentrations of all targeted carbonyls ranged from 13.6 to 18.6 mu g/m(3). Formaldehyde (C1) was the most abundant carbonyl, followed by acetaldehyde (C2) and acetone (C3K). The concentrations of C1 and C2 ranged from 3.3 to 8.5 mu g/m(3) and 2.3 to 4.4 mu g/m(3), respectively, which accounted for 23 to 42% and 18 to 26% respectively, to the total quantified carbonyls. The highest carbonyls levels were obtained in the dwelling located in an urban district with a mixture of industrial, commercial and residential areas. Much lower concentrations of carbonyls were measured in a light local traffic value was counted. Moderate correlations between individual combustion markers from vehicular emissions suggest the strong impacts from traffics to the indoor airs. The concentrations of C1 and C2 were compared with international indoor guidelines established by different authorities. A health assessment was conducted by estimation of inhalation cancer risk, implementing the inhalation unit risk values provided by Integrated Risk Information System (IRIS), associated with C1 and C2, which were 6.2 x 10(-5) and 7.7 x 10(-6), respectively. Even though the risks did not reach the action level (1 x 10(-4)), their health impact should not be overlooked. This kick-off indoor monitoring study provides valuable scientific data to the environmental science community since only limit data is available in Sri Lanka

Liver transplantation for acute-on-chronic liver failure

Purpose: To evaluate the outcome of liver transplantation for acute-on-chronic liver failure. Patients and methods: From November 1991 to December 2007, 517 patients underwent liver transplantation at Queen Mary Hospital, Hong Kong. Among them, 149 had acute-on-chronic liver failure as defined in the recent Asian Pacific Association for the Study of Liver Consensus Meeting. Their clinical data were reviewed and their survival outcomes were compared with those of patients who underwent liver transplantation for fulminant hepatic failure and for cirrhosis only in the same period. Results: The patients with acute-on-chronic liver failure included 50 patients having acute exacerbation of chronic hepatitis B and 99 cirrhotic patients with acute deterioration. Their median model for end-stage liver disease scores were 35 and 37, respectively. Preoperative infection (35%), hepatorenal syndrome (38%), and respiratory failure (28.8%) were common. One hundred and three patients received living donor liver grafts and 46 patients received deceased donor liver grafts. The hospital mortality rate was 4.7%. The 5-year survival rates were 93.2% for patients with acute exacerbation of chronic hepatitis B and 90.5% for cirrhotic patients with acute deterioration. The results were similar to those of the patients with fulminant hepatic failure (n = 37) and the patients having cirrhosis only (n = 301). Conclusions: Liver transplantation for acute-on-chronic liver failure is life-saving, and the survival rates it attains are similar to those attained by transplantation for other liver conditions.published_or_final_versionSpringer Open Choice, 21 Feb 201

Gene Expression Profiling of Liver Cancer Stem Cells by RNA-Sequencing

Background: Accumulating evidence supports that tumor growth and cancer relapse are driven by cancer stem cells. Our previous work has demonstrated the existence of CD90 + liver cancer stem cells (CSCs) in hepatocellular carcinoma (HCC). Nevertheless, the characteristics of these cells are still poorly understood. In this study, we employed a more sensitive RNA-sequencing (RNA-Seq) to compare the gene expression profiling of CD90 + cells sorted from tumor (CD90 +CSCs) with parallel non-tumorous liver tissues (CD90 +NTSCs) and elucidate the roles of putative target genes in hepatocarcinogenesis. Methodology/Principal Findings: CD90 + cells were sorted respectively from tumor and adjacent non-tumorous human liver tissues using fluorescence-activated cell sorting. The amplified RNAs of CD90 + cells from 3 HCC patients were subjected to RNA-Seq analysis. A differential gene expression profile was established between CD90 +CSCs and CD90 +NTSCs, and validated by quantitative real-time PCR (qRT-PCR) on the same set of amplified RNAs, and further confirmed in an independent cohort of 12 HCC patients. Five hundred genes were differentially expressed (119 up-regulated and 381 down-regulated genes) between CD90 +CSCs and CD90 +NTSCs. Gene ontology analysis indicated that the over-expressed genes in CD90 +CSCs were associated with inflammation, drug resistance and lipid metabolism. Among the differentially expressed genes, glypican-3 (GPC3), a member of glypican family, was markedly elevated in CD90 +CSCs compared to CD90 +NTSCs. Immunohistochemistry demonstrated that GPC3 was highly expressed in forty-two human liver tumor tissues but absent in adjacent non-tumorous liver tissues. Flow cytometry indicated that GPC3 was highly expressed in liver CD90 +CSCs and mature cancer cells in liver cancer cell lines and human liver tumor tissues. Furthermore, GPC3 expression was positively correlated with the number of CD90 +CSCs in liver tumor tissues. Conclusions/Significance: The identified genes, such as GPC3 that are distinctly expressed in liver CD90 +CSCs, may be promising gene candidates for HCC therapy without inducing damages to normal liver stem cells. © 2012 Ho et al.published_or_final_versio

Molecular and functional analysis of chromosome 11 in esophageal carcinomas

Esophageal cancer is an important cancer globally. It ranks eighth in incidence worldwide and seventh locally. Etiological studies have linked many factors to this malignancy. However, the molecular basis of the cancer is poorly understood. Previous studies showed that chromosome 11 is important in esophageal carcinomas. The aims of the present study were to identify possible region(s) containing tumor suppressor gene(s) on chromosome 11 related to esophageal pathogenesis and to investigate its functional role in this cancer. The first aim was achieved by using seventeen polymorphic microsatellite markers spanning the whole chromosome 11 to screen for loss of heterozygosity (LOH) in 38 primary esophageal squamous cell carcinomas. High rates of allelic loss were observed in two chromosomal regions, 11p15.5 and 11q22.3, which had also been reported in other cancers. This suggests the presence of tumor suppressor genes in these areas. The microcell-mediated chromosome transfer technique was used to determine the functional role of chromosome 11 in esophageal carcinogenesis. Chromosome 11 derived from a normal human fibroblast was introduced into the esophageal cancer cell line, T.Tn-6/TSI. Tumorigenic potentials of three chromosome 11-containing microcell hybrids were studied. All the hybrids showed complete suppression of tumorigenicity, including the one that probably received only a 11q fragment. This result indicated that the long arm of chromosome 11 may be sufficient to suppress the tumorigenic phenotype of the esophageal cancer cell line, T.Tn-6/TSI. Overall we demonstrated that chromosome 11 harbors tumor suppressor gene(s), probably localized to the 11q22.3 region, which is/are important for the tumorigenesis of the esophageal cancer

Identification of brain-derived neurotrophic factor (BDNF) as a novel angiogenic factor in tumor angiogenesis

published_or_final_versionSurgeryDoctoralDoctor of Philosoph

Brain-Derived Neurotrophic Factor Promotes Tumorigenesis via Induction of Neovascularization: Implication in Hepatocellular Carcinoma

Purpose: Brain-derived neurotrophic factor (BDNF) has emerged as a novel angiogenic factor, and yet its impact on tumorigenesis is unclear. This study aimed at investigating the roles of BDNF in angiogenesis and tumor development. Experimental Design: BDNF was overexpressed in a mouse endothelial cell (EC) line by stable transfection, and angiogenic properties of the transfectants were assessed. Microarray analysis was employed to explore the molecular pathways. The impact of modulating BDNF levels in two mouse EC lines on tumorigenic potential of a transformed mouse liver cell line was evaluated by an in vivo cotransplantation model. BDNF and tropomyosin receptor kinase B (TrkB) protein levels were determined in 50 pairs of human hepatocellular carcinoma (HCC) tissues by Western blotting and immunohistochemistry. Survival analysis was carried out to determine their clinical significance. Results: Overexpression of BDNF could promote EC proliferation, migration, invasion, and survival. Microarray and molecular studies showed that RhoA, caspase-9, caspase-3, growth arrest specific 6, and VEGF could mediate BDNF/TrkB-induced angiogenesis. The cotransplantation experiment showed that high BDNF-expressing ECs could facilitate tumor angiogenesis and growth, whereas knockdown of BDNF by short hairpin RNAs impaired such effects. Furthermore, examination on human HCC tissues revealed upregulation of BDNF and TrkB protein levels in 46.0% and 33.3% of the cases studied, respectively. Immunohistochemistry disclosed strong BDNF reactivity in both tumor and endothelial cells. High TrkB expression was associated with shorter overall survival. Conclusions: BDNF/TrkB system was crucial for tumor angiogenesis and growth, which may represent a potential target for antiangiogenic therapy in HCC. ©2011 AACR.link_to_subscribed_fulltex