Prognostic factors associated with the survival of oral and pharyngeal carcinoma in Taiwan

<p>Abstract</p> <p>Background</p> <p>In Taiwan, a distinct ethnic group variation in incidence and mortality rates has been suggested for most carcinomas. Our aim is to identify the role of prognostic factors associated with the survival of oral and pharyngeal carcinoma in Taiwan.</p> <p>Methods</p> <p>Taiwan Cancer Registry records of 9039 subjects diagnosed with oral and pharyngeal carcinoma were analyzed. The population was divided into three ethnic groups by residence, which were Taiwanese aborigines, Hakka and Hokkien communities. Five-year survival rates were estimated by Kaplan-Meier methods. Ethnic curves differed significantly by log-rank test; therefore separate models for Taiwanese aborigines, Hakka and Hokkien were carried out. The Cox multivariate proportional hazards model was used to examine the role of prognostic factors on ethnic survival.</p> <p>Results</p> <p>The five-year survival rates of oral and pharyngeal carcinoma were significantly poorer for Hokkien community (53.9%) and Taiwanese aborigines community (58.1%) compared with Hakka community (60.5%). The adjusted hazard ratio of Taiwanese aborigines versus Hakka was 1.07 (95%CI, 0.86–1.33) for oral and pharyngeal carcinoma mortality, and 1.16 (95%CI, 1.01–1.33) for Hokkien versus Hakka. Males had significantly poor prognosis than females. Subjects with tongue and/or mouth carcinoma presented the worst prognosis, whereas lip carcinoma had the best prognosis. Subjects with verrucous carcinoma had better survival than squamous cell carcinoma. Prognosis was the worst in elderly subjects, and subjects who underwent surgery had the highest survival rate.</p> <p>Conclusion</p> <p>Our study presented that predictive variables in oral and pharyngeal carcinoma survival have been: ethnic groups, period of diagnosis, gender, diagnostic age, anatomic site, morphologic type, and therapy.</p

Association between Cigarette Smoking and Hypoxanthine Guanine Phosphoribosyltransferase Activity

The aim of this study was to investigate the association between smoking behavior and hypoxanthine guanine phosphoribosyltransferase (HGPRT) activity. A cross-sectional study was performed of 82 men, including 38 non-smokers and 44 smokers. Inosine monophosphate (IMP), the product of HGPRT (used as the index of activity), was measured in peripheral blood mononuclear cells using high-performance liquid chromatography. The factors potentially associated with HGPRT activity included age, glutamyl oxaloacetic transaminase, glutamyl pyruvic transaminase, cholesterol, uric acid, triglycerides, creatinine, body mass index, gout, systolic blood pressure, diastolic blood pressure, alcohol consumption, and cigarette smoking. Mean HGPRT activity was 7.05 ± 3.44 nmol/106 viable cells/hour for all participants, and was significantly lower for smokers than for non-smokers (6.24 ± 3.40 vs 7.98 ± 3.28 nmol/106 viable cells/hour; p = 0.02). In addition, as the number of smoked cigarettes increased, the HGPRT activity decreased (p < 0.05). The age at onset of cigarette smoking showed a positive correlation with HGPRT activity after adjusting for smoking duration, serum uric acid, and cigarettes smoked per year using a multiple regression model (p < 0.001). We concluded that the greater the number of cigarettes smoked, the lower the HGPRT activity, and that HGPRT activity was higher in smokers who had started smoking later

Novel STAT3 Inhibitor LDOC1 Targets Phospho-JAK2 for Degradation by Interacting with LNX1 and Regulates the Aggressiveness of Lung Cancer

Meta-analysis revealed that Leucine Zipper Down-Regulated In Cancer 1 (LDOC1) increased methylation more in people with lung tumors than in those who were healthy and never smoked. Quantitative methylation-specific PCR revealed that cigarette smoke condensate (CSC) exposure drives LDOC1 promoter hypermethylation and silence in human bronchial cells. Immunohistochemistry studies showed that LDOC1 downregulation is associated with poor survival of patients with lung cancer. Loss and gain of LDOC1 functions enhanced and attenuated aggressive phenotypes in lung adenocarcinoma A549 and non&ndash;small cell lung carcinoma H1299 cell lines, respectively. We found that LDOC1 deficiency led to reinforcing a reciprocal loop of IL-6/JAK2/STAT3, through which LDOC1 mediates the cancer progression. LDOC1 knockdown considerably augmented tumorigenesis and the phosphorylation of JAK2 and STAT3 in vivo. Results from immunoprecipitation and immunofluorescent confocal microscopy indicated that LDOC1 negatively regulates JAK2 activity by forming multiple protein complexes with pJAK2 and E3 ubiquitin-protein ligase LNX1, and in turn, LDOC1 targets pJAK2 to cause ubiquitin-dependent proteasomal degradation. LDOC1 deficiency attenuates the interactions between LNX1 and pJAK2, leading to ineffective ubiquitination of pJAK2, which activates STAT3. Overall, our results elucidated a crucial role of LDOC1 in lung cancer and revealed how LDOC1 acts as a bridge between tobacco exposure and the IL-6/JAK2/STAT3 loop in this human malignancy

Genomewide Scan for Gout in Taiwanese Aborigines Reveals Linkage to Chromosome 4q25

Gout is a disorder of uric-acid metabolism. The Pacific Austronesian population, including Taiwanese aborigines, has a remarkably high prevalence of hyperuricemia and gout, which suggests a founder effect across the Pacific region. We report here a genomewide linkage study of 21 multiplex pedigrees with gout from an aboriginal tribe in Taiwan. From observations of familial clustering, early onset of gout, and clinically severe manifestations, we hypothesized that a major gene plays a role in this trait. Using 382 random polymorphic markers spread across 22 autosomes, we demonstrated a highly significant linkage for gout at marker D4S2623 on chromosome 4q25 (P=.0002 by nonparametric linkage [the NPL(all) statistic]; empirical P=.0006; LOD=4.3, P=4.4×10(-6) by logistic regression). When alcohol consumption was included as a covariate in the model, the LOD score increased to 5.66 (P=1.3×10(-6)). Quantitative traits, including serum uric acid and creatinine, also showed a moderate linkage to this region. To our knowledge, this is the first genome-scan report to identify a genetic locus harboring a gout-susceptibility gene

Visualization 1: Non-invasive manipulation of Drosophila behavior by two-photon excited red-activatable channelrhodopsin

This visualization shows the abdominal bending of a fly (Crz-Gal4 > UAS-ReaChR) fed 100 µM of all-trans-retinal illuminated by an effective peak power of 0.98 GW at 1250 nm. Originally published in Biomedical Optics Express on 01 November 2015 (boe-6-11-4344

Wdr4 promotes cerebellar development and locomotion through Arhgap17-mediated Rac1 activation

Abstract Patients with mutations of WDR4, a substrate adaptor of the CUL4 E3 ligase complex, develop cerebellar atrophy and gait phenotypes. However, the underlying mechanisms remain unexplored. Here, we identify a crucial role of Wdr4 in cerebellar development. Wdr4 deficiency in granule neuron progenitors (GNPs) not only reduces foliation and the sizes of external and internal granular layers but also compromises Purkinje neuron organization and the size of the molecular layer, leading to locomotion defects. Mechanistically, Wdr4 supports the proliferation of GNPs by preventing their cell cycle exit. This effect is mediated by Wdr4-induced ubiquitination and degradation of Arhgap17, thereby activating Rac1 to facilitate cell cycle progression. Disease-associated Wdr4 variants, however, cannot provide GNP cell cycle maintenance. Our study identifies Wdr4 as a previously unappreciated participant in cerebellar development and locomotion, providing potential insights into treatment strategies for diseases with WDR4 mutations, such as primordial dwarfism and Galloway-Mowat syndrome