Search

Background: Oral squamous cell carcinoma (OSCC) is one of the most common malignant neoplasms in Taiwan. Activation of the mTOR signaling pathway has been linked to decreased radiation responsiveness in human oral cancer, thus it limits efficacy of radiotherapy. To address this question, we investigated the effect of AZD2014, a novel small molecular ATP-competitive inhibitor of mTORC1 and mTORC2 kinase, as a radiosensitizer in primary OSCC and OSCC-derived cell line models. Methods: We isolated primary tumor cells from OSCC tissues and cell lines. AZD2014 was administered with and without ionizing radiation. The radiosensitizing effect of AZD2014 were then assessed using cell viability assays, clonogenic survival assays, and cell cycle analyses. Western blotting was used to detect protein expression. Results: Combination treatment with AZD2014 and irradiation resulted in significant reduction in OSCC cell line and primary OSCC cell colony formation due to the enhanced inhibition of AKT and both mTORC1 and mTORC2 activity. Pre-treatment with AZD2014 in irradiated oral cancer cells induced tumor cell cycle arrest at the G1 and G2/M phases, which led to disruption of cyclin D1-CDK4 and cyclin B1-CDC2 complexes. Moreover, AZD2014 synergized with radiation to promote both apoptosis and autophagy by increasing caspase-3 and LC3 in primary OSCC cells. Conclusions: These findings suggest that in irradiated OSCC cells, co-treatment with AZD2014, which targets mTORC1 and mTORC2 blockade, is an effective radiosensitizing strategy for oral squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Purpose: To understand the impact of socioeconomic status (SES) on the diagnosis of primary open-angle glaucoma (POAG) and primary angle closure glaucoma (PACG) in Taiwan. Methods: Subjects with glaucoma were identified from the National Health Insurance Research Database of year 2006, which included one million randomly selected insurants. Individuals who had ≥4 ambulatory visits within one year which had the diagnosis code of POAG (ICD-9-CM 365.11 or 365.12) or PACG (365.23) and concurrent prescription of anti-glaucoma medication or surgery were selected. Individual SES was represented by monthly income calculated from the insurance premium. Neighborhood SES was defined based on neighborhood household income averages. Urbanization level of habitation was categorized into 3 levels. The odds ratio of having POAG or PACG in subjects with different SES was evaluated by using multiple logistic regression analysis. Results: In total, 752 and 561 subjects with POAG and PACG, respectively, who were treated on a regular basis, were identified. The diagnosis of glaucoma was affected by age, gender, frequency of healthcare utilization, individual SES, and urbanization level of habitation. With the adjustment of age, gender, healthcare utilization, neighborhood SES and level of urbanization, subjects with lower income were more likely to be diagnosed as PACG, but less likely as POAG. Conclusions: Subjects with more frequent healthcare utilization were more likely to be diagnosed with glaucoma. Subjects with low SES were more susceptible to PACG, but subjects with high SES were more likely to be diagnosed as POAG. This information is useful for the design and target participant setting in glaucoma education and screening campaign to maximize the efficacy of limited resources in preventing glaucoma blindness. [ABSTRACT FROM AUTHOR]

Background: Identification of patients at risk of death from cancer surgery should aid in preoperative preparation. The purpose of this study is to assess and adjust the age-adjusted Charlson comorbidity index (ACCI) to identify cancer patients with increased risk of perioperative mortality. Methods: We identified 156,151 patients undergoing surgery for one of the ten common cancers between 2007 and 2011 in the Taiwan National Health Insurance Research Database. Half of the patients were randomly selected, and a multivariate logistic regression analysis was used to develop an adjusted-ACCI score for estimating the risk of 90-day mortality by variables from the original ACCI. The score was validated. The association between the score and perioperative mortality was analyzed. Results: The adjusted-ACCI score yield a better discrimination on mortality after cancer surgery than the original ACCI score, with c-statics of 0.75 versus 0.71. Over 80 years of age, 70–80 years, and renal disease had the strongest impact on mortality, hazard ratios 8.40, 3.63, and 3.09 (P < 0.001), respectively. The overall 90-day mortality rates in the entire cohort varied from 0.9%, 2.9%, 7.0%, and 13.2% in four risk groups stratifying by the adjusted-ACCI score; the adjusted hazard ratio for score 4–7, 8–11, and ≥ 12 was 2.84, 6.07, and 11.17 (P < 0.001), respectively, in 90-day mortality compared to score 0–3. Conclusions: The adjusted-ACCI score helps to identify patients with a higher risk of 90-day mortality after cancer surgery. It might be particularly helpful for preoperative evaluation of patients over 80 years of age. [ABSTRACT FROM AUTHOR]