Functional significance of the 3’-UTR in the mRNA of the stress-inducible protein CHOP/Gadd153

Poster Presentation: no. P-H041How translation is regulated by the 3’-untranslated region (3’-UTR) of many messenger RNA is presently not fully understood. This issue is addressed in this study with regard to those mRNA species that are specifically expressed in stressed cells, as exemplified by the stress-inducible CHOP/Gadd153 mRNA. A human genomic fragment with DNA sequence corresponding to the entire 3’-UTR plus an additional 500bp immediately downstream from the polyadenylation site of CHOP/Gadd153 mRNA was cloned into the pEGFP-C1 plasmid. The transcription of this pEGFP-CHOP plasmid in HeLa cells produced two mRNA transcripts due to utilization of either the polyA-signal of the CHOP/Gadd153 gene or the pEGFP-C1 plasmid itself. The EGFP protein level in the pEGFP-CHOP transfected cells was several-fold lower than cells expressing the control (pEGFP-C1). The deletion of the first 171bp from the 5’-end of the ...postprin

Cancer risk from gaseous carbonyl compounds in indoor environment generated from household coal combustion in Xuanwei, China

Airborne carbonyls were characterized from emitted indoor coal combustion. Samples were collected in Xuanwei (Yunnan Province), a region in China with a high rate of lung cancer. Eleven of 19 types of samples (58%) demonstrated formaldehyde concentrations higher than the World Health Organization exposure limit (a 30-min average of 100 μg m−3). Different positive significant correlations between glyoxal/methylglyoxal and formaldehyde/acetaldehyde concentrations were observed, suggesting possible different characteristics in emissions between two pairs of carbonyl compounds. A sample in the highest inhalation risk shows 29.2 times higher risk than the lowest sample, suggesting different coal sampling locations could contribute to the variation of inhalation risk. Inhabitants in Xuanwei also tend to spend more time cooking and more days per year indoors than the national average. The calculated cancer risk ranged from 2.2–63 × 10−5, which shows 13 types of samples at high-risk level. Cumulative effect in combination with different carbonyls could have contributed to the additive actual inhalation cancer risk. There is a need to explicitly address the health effects of environmentally relevant doses, considering life-long exposure in indoor dwellings

Gemcitabine and cisplatin in a multimodality treatment for locally advanced non-small cell lung cancer

The role of new cytotoxic agents like gemcitabine has not yet been proven in the neoadjuvant settings. We designed a phase II study to test the feasibility of using gemcitabine and cisplatin before local treatment for stage III non-small cell lung cancer patients. Patients received three cycles of induction chemotherapy of gemcitabine (1000 mg m−2, days 1, 8, 15) and cisplatin (90 mg m−2, day 15) every 4 weeks before evaluation for operability. Operable patients underwent radical resection. Inoperable patients and patients who had incomplete resection received concurrent chemoradiotherapy with daily low dose cisplatin. All patients who did not progress after local treatment received three more cycles of adjuvant chemotherapy of gemcitabine and cisplatin. Fifty-two patients received induction treatment. Two patients had complete response and 31 patients had partial response (response rate 63.5%) after induction chemotherapy. Thirty-six patients (69%) were operable. Eighteen patients (35%) had their tumours completely resected. Two patients had pathological complete response. Median overall survival was 19.1 months, projected 1-year survival was 66% and 2-year survival was 34%. Three cycles of gemcitabine and cisplatin is effective and can be used as induction treatment before surgery for locally advanced non-small cell lung cancer patients

The cancer genome atlas comprehensive molecular characterization of renal cell carcinoma

Renal cell carcinoma (RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD) ChRCC that associated with extremely poor survival

Diverse definitions of the early course of schizophrenia - a targeted literature review

Schizophrenia is a debilitating psychiatric disorder and patients experience significant comorbidity, especially cognitive and psychosocial deficits, already at the onset of disease. Previous research suggests that treatment during the earlier stages of disease reduces disease burden, and that a longer time of untreated psychosis has a negative impact on treatment outcomes. A targeted literature review was conducted to gain insight into the definitions currently used to describe patients with a recent diagnosis of schizophrenia in the early course of disease ('early' schizophrenia). A total of 483 relevant English-language publications of clinical guidelines and studies were identified for inclusion after searches of MEDLINE, MEDLINE In-Process, relevant clinical trial databases and Google for records published between January 2005 and October 2015. The extracted data revealed a wide variety of terminology and definitions used to describe patients with 'early' or 'recent-onset' schizophrenia, with no apparent consensus. The most commonly used criteria to define patients with early schizophrenia included experience of their first episode of schizophrenia or disease duration of less than 1, 2 or 5 years. These varied definitions likely result in substantial disparities of patient populations between studies and variable population heterogeneity. Better agreement on the definition of early schizophrenia could aid interpretation and comparison of studies in this patient population and consensus on definitions should allow for better identification and management of schizophrenia patients in the early course of their disease

Single particle analysis using time-resolved ICP-MS

Complete text of publication follows. It is of growing interest to characterize the metal contents of individual biological cells, nanostructures and even the functional groups of proteins. The particles can be introduced into the ICP individually and the metal contents of each particle are determined by time-resolved ICP-MS. However, detection of trace metals in the particles can be challenging (F. Li et al., Anal. Chem., 77 (2005) 1407-1413). Space charge effects in ICP-MS may also limit the accuracy of the measurement. In this study, the strategy of single particle analysis using time-resolved ICP-MS is examined. Nanoparticles of metal oxides, polyelectrolyte complexes and algal cells were used as test particles. The particles were suspended in water and introduced into the ICP using conventional solution nebulization. At particle number density of 1 x 106 ml-1, each aerosol contains no more than one particle. The particles are introduced into the ICP individually. Each particle in ICP produces a plume of analyte ions which are detected as a current spike in the mass spectrometer. The experimental setup for sample introduction and ion detection will be discussed. Strategy to enhance the detection sensitivity of trace metals in the particles and improve the accuracy of the measurement will also be discussed. The authors kindly acknowledge the financial support from the Department of Chemistry of The University of Hong Kong and the Committee on Research and Conference Grants