The interaction between C35 and ΔNp73 promotes chemo-resistance in ovarian cancer cells.

BACKGROUND: The purpose of this study was to characterise the oncogenic roles of C35, a novel protein binding partner of ΔNp73, in ovarian cancer and to investigate the functional significance of C35-ΔNp73 interaction in the regulation of chemo-resistance. METHODS: C35 expression was evaluated by quantitative real-time PCR in human ovarian cancer tissues and cell lines. The aggressiveness of ovarian cancer cells overexpressing C35 was examined by cell proliferation, migration, soft agar and nude mouse xenograft. The significance of C35-ΔNp73 interaction in chemo-resistance was evaluated by apoptosis assays and cell viability after cisplatin treatment. RESULTS: The expression of C35 was significantly enhanced in human ovarian cancer tissues. Overexpression of C35 augmented proliferation, migration and tumourigenicity in ovarian cancer cell lines. C35 knockdown inhibited cell motility and cell growth. The co-expression of C35 and ΔNp73 by transient or stable transfection in ovarian cancer cells induced greater resistance to cisplatin treatment than did transfection with C35 or ΔNp73 alone. The cisplatin resistance was demonstrated to be caused by increased AKT and NFκB activity induced by C35-ΔNp73. CONCLUSION: Our results suggest that ΔNp73 might cooperate with C35 to promote tumour progression and contribute to cisplatin resistance in ovarian cancer cells. Future studies of the functional roles of ΔNp73 and C35 will provide insight that will aid in the establishment of new strategies and more effective therapies.

Foetal exposure to maternal passive smoking is associated with childhood asthma, allergic rhinitis, and eczema.

OBJECTIVE: We examined the hypothesis that foetal exposure to maternal passive smoking is associated with childhood asthma, allergic rhinitis, and eczema. METHODS. The study was a population-based cross-sectional survey of Hong Kong Chinese children aged ≤14 years carried out in 2005 to 2006. RESULTS. Foetal exposure to maternal passive smoking was significantly associated with wheeze ever (OR 2.05; 95% CI 1.58-2.67), current wheeze (OR 2.06; 95% CI 1.48-2.86), allergic rhinitis ever (OR 1.22; 95% CI 1.09-1.37), and eczema ever (OR 1.61; 95% CI 1.38-1.87). Foetal exposure to maternal active smoking was significantly associated with asthma ever (OR 2.10; 95% CI 1.14-3.84), wheeze ever (OR 2.46; 95% CI 1.27-4.78), and current wheeze (OR 2.74; 95% CI 1.24-6.01) but not with allergic rhinitis ever (OR 1.01; 95% CI 0.70-1.46) or eczema ever (OR 1.38; 95% CI 0.87-2.18). The dose response relationship between wheeze ever and current wheeze with increasing exposure, from no exposure to maternal passive smoking and then to maternal active smoking, further supports causality. CONCLUSION. There is significant association between foetal exposure to maternal passive smoking and maternal active smoking with childhood asthma and related atopic illnesses. Further studies are warranted to explore the potential causal relationship.

Evaluation of the molecular Xpert Xpress Flu/RSV assay vs. Alere i Influenza A & B assay for rapid detection of influenza viruses.

A new FDA-approved Xpert Xpress Flu/RSV assay has been released for rapid influenza virus detection. We collected 134 nasopharyngeal specimens to compare the diagnostic performance of the Xpert assay and the Alere i Influenza A & B assay for influenza A and B virus detection. The Xpert assay demonstrated 100% and 96.3% sensitivity to influenza A and influenza B virus respectively. Its specificity was 100% for both viruses. The Alere i assay demonstrated slightly lower sensitivity but similar specificity to the Xpert Xpress assay. Although the Xpert assay (30 min) required longer processing time than the Alere assay (15 min), the handling procedure of the Alere assay was more complicated than the Xpert assay. As the GenXpert system has higher throughput than the Alere system, it is more suitable for hospital clinical laboratories. Overall, the new Xpert Xpress Flu/RSV assay is a reliable and useful tool for rapid influenza detection.

DLX1 acts as a crucial target of FOXM1 to promote ovarian cancer aggressiveness by enhancing TGF-ß/SMAD4 signaling.

Recent evidence from a comprehensive genome analysis and functional studies have revealed that FOXM1 is a crucial metastatic regulator that drives cancer progression. However, the regulatory mechanism by which FOXM1 exerts its metastatic functions in cancer cells remains obscure. Here, we report that DLX1 acts as a FOXM1 downstream target, exerting pro-metastatic function in ovarian cancers. Both FOXM1 isoforms (FOXM1B or FOXM1C) could transcriptionally upregulate DLX1 through two conserved binding sites, located at +61 to +69bp downstream (TFBS1) and -675 to -667bp upstream (TFBS2) of the DLX1 promoter, respectively. This regulation was further accentuated by the significant correlation between the nuclear expression of FOXM1 and DLX1 in high-grade serous ovarian cancers. Functionally, the ectopic expression of DLX1 promoted ovarian cancer cell growth, cell migration/invasion and intraperitoneal dissemination of ovarian cancer in mice, whereas small interfering RNA-mediated DLX1 knockdown in FOXM1-overexpressing ovarian cancer cells abrogated these oncogenic capacities. In contrast, depletion of FOXM1 by shRNAi only partially attenuated tumor growth and exerted almost no effect on cell migration/invasion and the intraperitoneal dissemination of DLX1-overexpressing ovarian cancer cells. Furthermore, the mechanistic studies showed that DLX1 positively modulates transforming growth factor-ß (TGF-ß) signaling by upregulating PAI-1 and JUNB through direct interaction with SMAD4 in the nucleus upon TGF-ß1 induction. Taken together, these data strongly suggest that DLX1 has a pivotal role in FOXM1 signaling to promote cancer aggressiveness through intensifying TGF-ß/SMAD4 signaling in high-grade serous ovarian cancer cells.

Chronic health problems and health-related quality of life in Chinese children and adolescents: a population-based study in Hong Kong.

OBJECTIVE: We examined the association of different chronic physical and mental conditions, individually or comorbidly on health-related quality of life (QoL) in Chinese children aged ≤14 years in Hong Kong. DESIGN: Population-based cross-sectional survey. PARTICIPANTS: Approximately 7500 Chinese children aged <14 years in Hong Kong. INTERVENTIONS: Nil. PRIMARY AND SECONDARY OUTCOME MEASURES: Various health concepts of validated Chinese version of Child Health Questionnaire (CHQ), a health-related QoL questionnaire in children. RESULT: There was significant association of physical and mental health conditions, either individually or comorbidly, on the various concepts of CHQ. Children with mental health problems were apparently more affected than those with physical health problems. Chronic renal disease and congenital malformation were the physical health conditions associated with the lowest scores in CHQ concepts in children aged 5-10 years and aged 10-14 years, respectively. Behavioural problem was the mental health condition associated with the lowest score in CHQ concepts in both age groups. CONCLUSIONS: Our study shows important information concerning the prevalence of different health conditions and its association, either individually or comorbidly on the QoL in a representative sample of Chinese children in HK.

Changing epidemiology of measles in Hong Kong from 1961 to 1990--impact of a measles vaccination program.

With the use of measles vaccine since 1967, Hong Kong has experienced a low incidence of measles until a major outbreak in 1988. A shift in the distribution of susceptible children to older age groups was suddenly accelerated in the 1988 outbreak. The attack rate increased by 18.9-fold for children greater than 10 years old, while that for those in the best-protected age group of 1-4 years was only 2.2-fold. Of the cases during that outbreak, 56.3% would have been considered preventable with the present vaccination regimen, and vaccine failures accounted for only 20.4% of the cases. Present control strategies aim at increasing the coverage rate rather than introducing a two-dose regimen, which may be necessary when vaccine failures account for a larger proportion of measles cases.

Outbreak of Vibrio cholerae 01 in Hong Kong related to contaminated fish tank water.

An outbreak of 12 cholera cases, caused by Vibrio cholerae eltor inaba, occurred in Hong Kong during a three week period in June-July 1994. Only adults of both sexes were affected. Epidemiological investigations showed linkage in all cases with consumption of seafood, including shellfish, mantis shrimps and crabs. Microbiological findings demonstrated that contaminated seawater in fish tanks used for keeping alive these seafoods is the most likely vehicle of transmission. Aggressive control measures, promptly instituted, included prohibition of use of contaminated typhoon shelter water in fish tanks, use of seawater with E. coli counts below 610 organisms/100 ml, and the banning of unlicensed food sampans in typhoon shelters. These measures, coupled with public announcements and an active health education campaign on food safety and personal hygiene, abruptly terminated the outbreak. Places which practise the use of seawater, from probable contaminated sources, to keep alive their seafood for human consumption should be alerted to the possibility of transmission of Vibrio cholerae through this route.