1-Aminocyclopropane-1-carboxylate (ACC) Deaminase Gene in Pseudomonas azotoformans Is Associated with the Amelioration of Salinity Stress in Tomato.

Although bacteria with 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity have been used to mitigate biotic and abiotic stresses in crops, it is not well known whether the ACC deaminase gene (acdS) in Pseudomonas azotoformans is related to the alleviation of salt stress by the bacterium. This study aimed to evaluate the effects of acdS in P. azotoformans strain CHB 1107 on the nutrient uptake and growth of tomato plants under salt stress. The acdS mutant (CHB 1107 M) of P. azotoformans CHB 1107 was obtained through bacterial conjugation. Wild-type (CHB 1107 WT) and CHB 1107 M were used to inoculate tomato plants grown in a soil or solution with an electrical conductivity of 6 dS/m adjusted by NaCl. CHB 1107 M completely lost the ability to produce ACC deaminase, whereas the complementation of acdS in CHB 1107 M preserved its ACC deaminase activity. CHB 1107 WT significantly reduced the production of ethylene and proline by tomato plants under salt stress, increasing the shoot and root dry weights of tomato plants compared with the noninoculated control and CHB 1107 M. In addition, tomato plants inoculated with CHB 1107 M showed a significant reduction in K (27.5%), Ca (23.0%), and Mn uptake (17.5%) compared with those inoculated with CHB 1107 WT. In contrast, CHB 1107 WT significantly reduced Na uptake by tomato plants in comparison to CHB 1107 M in saline soil conditions. In addition, the inoculation of tomato plants with CHB 1107 WT resulted in a higher K/Na ratio than in those inoculated with CHB 1107 M and the noninoculated control. These findings suggest that acdS in P. azotoformans is associated with the amelioration of salinity stress in tomato. Plant transformation with acdS and the field application of P. azotoformans may be used as potential management tools for crops under salt stress.

Comparative Study of the Safety and Efficacy of First-Line Cisplatin and Carboplatin Chemotherapy in Elderly Patients with Metastatic Urothelial Carcinoma.

OBJECTIVES: Platinum-based chemotherapy is the standard treatment for metastatic urothelial carcinoma (mUC). However, considering elderly patients often experience comorbidities and frailty, the utility of cisplatin-based chemotherapy for elderly patients is still debatable. We conducted this study to compare the safety and efficacy of carboplatin and cisplatin in elderly patients with mUC. METHODS: This retrospective study enrolled elderly patients with mUC (defined as aged ≥70 years) who underwent first-line platinum-based chemotherapy between September 2001 and October 2018. The primary endpoints were chemotherapy-related adverse events (AEs), including treatment-related hospitalization or death. The secondary outcomes were overall survival (OS) and progression-free survival calculated by Kaplan-Meier analysis. RESULTS: In total, 108 elderly patients with mUC were enrolled and allocated into the cisplatin or carboplatin group. Patients treated with carboplatin-based chemotherapy had a significantly higher incidence of all grade ≥3 AEs (78.8 vs. 50.0%, p = 0.008) than those on cisplatin. AE-related hospitalization (47.5 vs. 19.1%, p = 0.002) and treatment-related death (17.5 vs. 4.4%, p = 0.02) were significantly increased in the carboplatin group. In the univariate analysis, the median OS in the cisplatin group was significantly increased compared with the carboplatin group (13.6 vs. 7.2 months, p = 0.045). The Cox multivariate regression model indicated that leukocytosis (HR 3.17, 95% CI 1.84-5.46, p < 0.001) and anemia (HR 2.02, 95% CI 1.11-3.65, p = 0.02) were independent prognostic factors. CONCLUSION: Elderly patients with mUC treated with cisplatin-based chemotherapy had better survival and safety profiles than those treated with carboplatin. Age itself was not a crucial factor in determining cisplatin eligibility.

Impact of Prognostic Nutritional Index on Overall Survival for Patients with Metastatic Urothelial Carcinoma.

Background: Prognostic nutritional index (PNI) has been studied in various types of cancer which is significantly correlated with prognosis. The study aims to investigate the predictive role of PNI in patients with metastatic urothelial carcinoma (mUC) treated with systemic chemotherapy. Methods: We retrospectively reviewed 141 patients with mUC who received systemic chemotherapy. PNI was calculated as 10 × serum albumin concentration (g/dL) + 0.005 × lymphocyte count (number/mm2). The optimal cut-off value for PNI was estimated by using receiver operating curve analysis. Independent factors associated with progression-free survival (PFS) and overall survival (OS) were determined by Cox proportional regression models. Results: The recommended cut-off value for PNI was 40. Patients with a low PNI had more visceral metastases (p < 0.0001), leukocytosis (p = 0.006), and anemia (p < 0.0001). On univariate analysis, patients with a low PNI had poor OS than those with a high PNI (p < 0.0001). The multivariate analysis showed PNI was an independent factor to predict OS (p = 0.001). Conclusions: Our study showed PNI is an independent prognostic factor in patients with mUC. Our work is clinically useful for anticipation of outcomes, risks stratification in clinical studies as well as patients counseling.

The clinical impact of supraclavicular lymph node metastasis in patients with locally advanced esophageal squamous cell carcinoma receiving curative concurrent chemoradiotherapy.

BACKGROUND: To evaluate the clinical significance of supraclavicular lymph node (SCLN) in patients with locally advanced esophageal squamous cell carcinoma (ESCC) receiving curative concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: We retrospectively analyzed all 369 locally advanced ESCC patients treated with CCRT between 2000 and 2015, including 70 patients with SCLN metastasis and 299 patients without SCLN metastasis. RESULTS: For these locally advanced ESCC patients treated with curative CCRT, N0-2 were significantly associated with superior progression-free survival (PFS) and overall survival (OS) in univariate and multivariable analyses. However, there were no significant differences in PFS and OS between the SCLN metastasis and non-SCLN metastasis groups; a subgroup analysis also revealed there was no significant differences in PFS and OS between patients with and without SCLN metastasis either in the N0-2 or in the N3 subgroup analysis. CONCLUSIONS: Our study suggests that SCLN metastasis is not a prognostic factor in locally advanced ESCC patients receiving curative CCRT, and that SCLNs should be considered to be regional LNs and treated with curative intent.

Prognostic impact of tumor infiltrating lymphocytes on patients with metastatic urothelial carcinoma receiving platinum based chemotherapy.

The impact of tumor infiltrating lymphocytes (TILs) on survival was confirmed in various cancer types. Our study aims to investigate the prognostic role of TILs on survival in patients with metastatic urothelial carcinoma (mUC) receiving platinum based chemotherapy. Patients who were diagnosed to have pathologically proved mUC between 1997 and 2016 and received palliative chemotherapy with platinum based regimen were recruited into our study. Kaplan-Meier curves and Cox regression analysis were constructed for overall survival (OS). A total of 259 mUC patients were enrolled into our study with median age 63 years and median follow-up visit 13.5 months. Of these patients, 179 (69%) had intense TILs and 80 (31%) had non-intense TILs. The median OS were 15.7 vs. 6.7 months (P = < 0.001) for patients with intense TILs and non-intense TILs, respectively. Subgroup analysis showed that TILs was both prognostically significant no matter for urothelial carcinoma of bladder and upper tract urothelial carcinoma. Multivariate analysis showed that TILs were strongly prognostic factors related to OS. Our study suggested mUC patients with intense TILs were independently associated with survival. Based on our study, TILs is clinically useful for outcomes anticipation and risk stratification, as well as patients counseling.

Reducing health care-associated infections by implementing separated environmental cleaning management measures by using disposable wipes of four colors.

Background: Environmental cleaning is a fundamental principle of infection control in health care settings. We determined whether implementing separated environmental cleaning management measures in MICU reduced the density of HAI. Methods: We performed a 4-month prospective cohort intervention study between August and December 2013, at the MICU of Cathay General hospital. We arranged a training program for all the cleaning staff regarding separated environmental cleaning management measures by using disposable wipes of four colors to clean the patients' bedside areas, areas at a high risk of contamination, paperwork areas, and public areas. Fifteen high-touch surfaces were selected for cleanliness evaluation by using the adenosine triphosphate (ATP) bioluminescence test. Then data regarding HAI densities in the MICU were collected during the baseline, intervention, and late periods. Results: A total of 120 ATP readings were obtained. The total number of clean high-touch surfaces increased from 13% to 53%, whereas that of unclean high-touch surface decreased from 47% to 20%. The densities of HAI were 14.32‰ and 14.90‰ during the baseline and intervention periods, respectively. The HAI density did not decrease after the intervention period, but it decreased to 9.07‰ during the late period. Conclusion: Implementing separated environmental cleaning management measures by using disposable wipes of four colors effectively improves cleanliness in MICU environments. However, no decrease in HAI density was observed within the study period. Considering that achieving high levels of hand-hygiene adherence is difficult, improving environmental cleaning is a crucial adjunctive measure for reducing the incidence of HAIs.

The prognostic significance of celiac lymph node metastasis in patients with locally advanced esophageal squamous cell carcinoma receiving curative concurrent chemoradiotherapy.

BACKGROUND: To evaluate the clinical outcomes of celiac lymph node (LN) metastasis in patients with locally advanced esophageal squamous cell carcinoma (ESCC) receiving curative concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: A total of 375 stage III ESCC patients were identified, including 51 patients with celiac LN metastasis and 324 patients without celiac LN metastasis. Among these 324 patients without celiac LN metastasis, 51 were matched with the 51 patients with celiac LN metastasis using the propensity score matching method. RESULTS: Overall, the celiac LN metastasis group had worse progression-free survival (PFS) and overall survival (OS) than the non-celiac LN metastasis group and the matched non-celiac LN metastasis group. For the ESCC patients with celiac LN metastasis, lower third ESCC was significantly associated with superior PFS and OS. For patients with upper/middle third ESCC, the celiac LN metastasis group had worse PFS and OS than the non-celiac LN metastasis group and the matched non-celiac LN metastasis group. For patients with lower third ESCC, there were no significant differences in PFS and OS between these groups. CONCLUSIONS: Our study suggests celiac LN metastasis is a poor prognostic factor for locally advanced ESCC patients receiving curative CCRT. Among these ESCC patients with celiac LN metastasis, tumor location is a strongly prognostic factor, indicating patients with lower third ESCC have better PFS and OS than those with upper/middle third ESCC. The 6th American Joint Committee on Cancer staging system seems more favorable than 7th edition in the definition of celiac LNs for those patients.

Novel Inflammation-Based Prognostic Score for Predicting Survival in Patients with Metastatic Urothelial Carcinoma.

PURPOSE: We developed a novel inflammation-based model (NPS), which consisted of a neutrophil to lymphocyte ratio (NLR) and platelet count (PC), for assessing the prognostic role in patients with metastatic urothelial carcinoma (UC). MATERIALS AND METHODS: We performed a retrospective analysis of patients with metastatic UC who underwent systemic chemotherapy between January 1997 and December 2014 in Kaohsiung Chang Gung Memorial Hospital. The defined cutoff values for the NLR and PC were 3.0 and 400 × 103/µL, respectively. Patients were scored 1 for either an elevated NLR or PC, and 0 otherwise. The NPS was calculated by summing the scores, ranging from 0 to 2. The primary endpoint was overall survival (OS) by using Kaplan-Meier analysis. Multivariate Cox regression analysis was used to identify the independent prognostic factors for OS. RESULTS: In total, 256 metastatic UC patients were enrolled. Univariate analysis revealed that patients with either a high NLR or PC had a significantly shorter survival rate compared with those with a low NLR (P = .001) or PC (P < .0001). The median OS in patients with NPS 0, 1, and 2 was 19.0, 12.8, and 9.3 months, respectively (P < .0001). Multivariate analysis revealed that NPS, along with the histologic variant, liver metastasis, age, and white cell count, was an independent factor facilitating OS prediction (hazard ratio 1.64, 95% confidence interval 1.20-2.24, P = .002). CONCLUSION: The NLR and PC are independent prognostic factors for OS in patients with metastatic UC. The NPS model has excellent discriminant ability for OS.

A Survival Scoring System for Non-Small Cell Lung Cancer Patients with De Novo Bone Metastases.

In the pre-tyrosine kinase inhibitors (TKIs) era, non-small cell lung cancer (NSCLC) patients with de novo bone metastases had a worse prognosis than those without. However, whether epidermal growth factor receptor (EGFR)-TKIs affect the outcomes of EGFR mutant NSCLC patients with de novo bone metastases has not been well studied thus far. We retrospectively studied the effect of EGFR mutation status and first-line EGFR-TKIs on patient outcomes and created a survival scoring system for NSCLC patients with de novo bone metastases. This retrospective study evaluated 1510 NSCLC patients diagnosed between November 2010 and March 2014. Among these patients, 234 patients had de novo bone metastases. We found that 121 of these 234 patients (51.7%) had positive EGFR mutation tests, and a positive EGFR mutation test significantly affected overall survival (OS) (EGFR mutant: 15.2 months, EGFR wild type: 6.5 months; p < 0.001). Other prognostic factors significant in the multivariable analysis for NSCLC with de novo bone metastases included Eastern Cooperative Oncology Group performance status (PS) (OS; PS 0-2: 11.2 months, PS 3-4: 4.9 months; p = 0.002), presence of extraosseous metastases (OS; with extraosseous metastases: 8.8 months, without extraosseous metastases: 14.0 months; p = 0.008), blood lymphocyte-to-monocyte ratio (LMR) (OS; LMR > 3.1: 17.1months, LMR ≤ 3.1: 6.9months; p < 0.001). A positive EGFR mutation status reversed the poor outcomes of NSCLC patients with de novo bone metastases. A simple and useful survival scoring system including the above clinical parameters was thus created for NSCLC patients with de novo bone metastases.

Management of Powdery Mildew in Squash by Plant and Alga Extract Biopesticides.

Although many fungicides are registered for use to control powdery mildew on cucurbits, management of resistance to fungicides in pathogen populations still remains a major challenge. Two biopesticides Regalia SC and HMO 736 were evaluated in the greenhouse and field for their efficacy against powdery mildew in squash. In greenhouses, Regalia SC alone significantly (P < 0.05) reduced powdery mildew compared to the nontreated control, and was as effective as the chemical standard Procure 480SC (triflumizole). In alternation with Procure 480SC, Regalia SC demonstrated greater or equivalent effects on reducing the disease. HMO 736 alone showed varying levels of disease control, but alternating with Procure 480SC significantly improved control efficacy. In addition, application of Regalia SC or HMO 736 each in alternation with Procure 480SC significantly increased the chlorophyll content in leaves and the total fresh weight of squash plants, when compared with the water control, Regalia SC and HMO 736 alone. In field trials, application of Regalia SC and HMO 736 each alone significantly reduced disease severity in one of two field trials during the early stage of disease development, but not during later stages when disease pressure became high. Both Regalia SC and HMO 736 each applied in alternation with Procure 480SC significantly improved the control efficacy compared to Procure 480SC alone. Results from this study demonstrated that an integrated management program can be developed for powdery mildew in squash by integrating the biopesticides Regalia SC, HMO 736 with the chemical fungicide Procure 480SC.

Impact of clinical parameters and systemic inflammatory status on epidermal growth factor receptor-mutant non-small cell lung cancer patients readministration with epidermal growth factor receptor tyrosine kinase inhibitors.

BACKGROUND: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) readministration to lung cancer patients is common owing to the few options available. Impact of clinical factors on prognosis of EGFR-mutant non-small cell lung cancer (NSCLC) patients receiving EGFR-TKI readministration after first-line EGFR-TKI failure and a period of TKI holiday remains unclear. Through this retrospective study, we aimed to understand the impact of clinical factors in such patients. METHODS: Of 1386 cases diagnosed between December 2010 and December 2013, 80 EGFR-mutant NSCLC patients who were readministered TKIs after failure of first-line TKIs and intercalated with at least one cycle of cytotoxic agent were included. We evaluated clinical factors that may influence prognosis of TKI readministration as well as systemic inflammatory status in terms of neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR). Baseline NLR and LMR were estimated at the beginning of TKI readministration and trends of NLR and LMR were change amount from patients receiving first-Line TKIs to TKIs readministration. RESULTS: Median survival time since TKI readministration was 7.0 months. In the univariable analysis, progression free survival (PFS) of first-line TKIs, baseline NLR and LMR, and trend of LMR were prognostic factors in patients receiving TKIs readministration. In the multivariate analysis, only PFS of first-line TKIs (p < 0.001), baseline NLR (p = 0.037), and trend of LMR (p = 0.004) were prognostic factors. CONCLUSION: Longer PFS of first-line TKIs, low baseline NLR, and high trend of LMR were good prognostic factors in EGFR-mutant NSCLC patients receiving TKI readministration.

Photoprotective Effects of Cycloheterophyllin against UVA-Induced Damage and Oxidative Stress in Human Dermal Fibroblasts.

Ultraviolet (UV) radiation, particularly ultraviolet A (UVA), is known to play a major role in photoaging of the human skin. Many studies have demonstrated that UV exposure causes the skin cells to generate reactive oxygen species and activates the mitogen-activated protein kinase (MAPK) pathway. Previous studies have also demonstrated that cycloheterophyllin has an antioxidant effect and can effectively scavenge free radicals. Extending the aforementioned investigations, in this study, human dermal fibroblasts were used to investigate the protective effect of cycloheterophyllin against UV-induced damage. We found that cycloheterophyllin not only significantly increased cell viability, but also attenuated the phosphorylation of MAPK after UVA exposure. Furthermore, cycloheterophyllin could reduce hydrogen peroxide (H2O2) generation and down-regulate H2O2-induced MAPK phosphorylation. In the in vivo studies, the topical application of cycloheterophyllin before UVA irradiation significantly decreased trans-epidermal water loss (TEWL), erythema, and blood flow rate. These results indicate that cycloheterophyllin is a photoprotective agent that inhibits UVA-induced oxidative stress and damage, and could be used in the research on and prevention of skin photoaging.

Tailored Selection of First-Line Cisplatin-Based Chemotherapy in Patients with Metastatic Urothelial Carcinoma of Bladder.

PURPOSE: Methotrexate, vinblastine, doxorubicin plus cisplatin (MVAC) and gemcitabine plus cisplatin (GC) are both effective first-line chemotherapy. We explore the responsive variables of MVAC and GC for patients with metastatic urothelial carcinoma of bladder (mUCB). MATERIALS AND METHODS: Patients who were initially diagnosed to have mUCB and received MVAC or GC as metastatic first-line chemotherapy between 2000 and 2014 at Kaohsiung Chang Gung Memorial Hospital were reviewed. Totally, 130 patients were enrolled into our study. Univariable Cox proportional hazard models were constructed for OS. Hazard ratio (HR) and 95% confidence intervals (CIs) was also presented. RESULTS: There were 50 patients (38%) in the MVAC group and 80 patients (62%) in the GC group. The median OS was insignificantly different between MVAC and GC groups, accounting for 17.0 and 14.4 months (P = 0.214), respectively. OS of MVAC group was significantly longer with regard to age ≦ 60 years (HR: 0.38, 95% CI: 0.12-0.97, P = 0.036), pure urothelial carcinoma (HR: 0.56, 95% CI: 0.34-0.90, P = 0.015), > 1 metastatic sites (HR: 0.19, 95% CI: 0.08-0.44, P = < 0.001), and neutrophil to lymphocyte ratio > 3(HR: 0.45, 95% CI: 0.25-0.81, P = 0.006), while OS with GC group was significantly longer with regard to variant urothelial carcinoma (HR: 0.56, 95% CI: 0.34-0.90, P = 0.015). CONCLUSIONS: Our study disclosed the predictive factors of different regimen for mUCB. These results have clinical implication for physicians who treat patients with mUCB.

Advanced non-Small cell lung cancer patients at the extremes of age in the era of epidermal growth factor receptor tyrosine kinase inhibitors.

OBJECTIVES: The clinical characteristics and survival of very young (≤40 years) and very old (>80years) patients with advanced non-small cell lung cancer (NSCLC) are distinct. However, the benefits of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) to patients at the extremes of age with NSCLC harboring EGFR mutation have not been well studied. We retrospectively studied the effect of extreme age on patients' clinical characteristics and prognosis. MATERIALS AND METHODS: Of 1510 lung cancer patients diagnosed between November 2010 and March 2014, 555 patients who were tested for EGFR mutations were included. Patients were divided into the following groups according to age: young (≤40 years), lower medium (41-60 years), higher medium (61-80years), and very old (>80years). RESULTS: Of the 555 patients, 20 (3.6%) patients were aged ≤40 years and 60 (10.8%) patients were aged >80years. Young NSCLC patients had a lower BMI (p=0.003), more brain (p=0.016) and bone metastases (p=0.002) Very young lung cancer patients still have poor prognosis even they were EGFR mutant. (EGFR mutant vs. wild type patients, OS: 12 vs. 7.3 months, p=0.215) Very old NSCLC patients had a lower BMI (p=0.003) and poor ECOG PS (p=0.028). Positive EGFR mutation test reverses poor prognosis of elderly NSCLC patients. (EGFR mutant vs. wild type patients, OS: 13.2 vs. 4.9 months, p=0.003) CONCLUSION: We observed EGFR mutations reverse the poor prognosis of old patients with NSCLC. However, young patients with lung cancer have a poor prognosis even if they harbor EGFR mutations.

Prognostic model to predict survival in patients with metastatic upper tract urothelial carcinoma treated with cisplatin-based chemotherapy.

OBJECTIVES: To create a novel prognostic model to predict survival in metastatic upper tract urothelial carcinoma patients treated with cisplatin-based chemotherapy. METHODS: After institutional review board approval, patients who had metastatic upper tract urothelial carcinoma and were treated with cisplatin based chemotherapy from 2000 to 2012 at Kaohsiung Chang Gung Memorial Hospital were retrospectively reviewed. Significantly predictive factors were identified by multivariate Cox regress analyses. Kaplan-Meier curves were plotted to estimate overall survival. Several prognostic models were validated by using our cohort, and Harrell's c-index was calculated to evaluate their predicting performances. RESULTS: The present study consisted of 136 patients with a median age of 62 years and a median follow-up visit of 13.6 months. Multivariate analyses showed that renal function, performance status, liver metastasis and number of metastatic sites was independently related to survival. Based on these four variables, we constructed a prognostic model "renal function, performance status, liver metastasis, number of metastatic sites" with significantly different survival (P < 0.001). C-index results were renal function, performance status, liver metastasis, number of metastatic sites model 0.80 (0.69-0.90), Bajorin model 0.72 (0.61-0.83), Taguchi model 0.77 (0.67-0.87) and Tanaka model 0.78 (0.69-0.88). Our renal function, performance status, liver metastasis, number of metastatic sites prognostic model achieved the highest c-index in this study. CONCLUSIONS: Our renal function, performance status, liver metastasis, number of metastatic sites prognostic model could be useful for providing prognostic information on survival in patients with metastatic upper tract urothelial carcinoma.

The comparison of oncologic outcomes between metastatic upper tract urothelial carcinoma and urothelial carcinoma of the bladder after cisplatin-based chemotherapy.

OBJECTIVE: To compare the oncologic outcomes and prognostic factors between metastatic upper tract urothelial carcinoma (UTUC) and UC of the bladder (UCB) after cisplatin-based chemotherapy. MATERIALS AND METHODS: We retrospectively reviewed patients with metastatic UTUC and UCB after methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) or gemcitabine/cisplatin chemotherapy between 1997 and 2014 at Kaohsiung Chang Gung Memorial Hospital. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Univariate and multivariate analyses with Cox proportional hazard models were also performed to assess the effect of prognostic factors. RESULTS: Totally, 203 patients were enrolled into our study, including 120 patients with UTUC and 83 patients with UCB. For patients with UTUC, the median PFS was 7.3 months vs. 4.0 months (P<0.001), and the median OS was 17.0 months vs. 10.5 months (P<0.001) for MVAC and gemcitabine/cisplatin, respectively. For patients with UCB, the median PFS (P = 0.35) and OS (P = 0.06) of the 2 groups were insignificant. In multivariate analyses, number of metastatic sites was the identical prognostic factor for OS between UTUC (hazard ratio [HR] = 2.74; 95% CI: 1.63-4.62; P<0.001) and UCB (HR = 3.12; 95% CI: 1.52-6.39; P = 0.002). Presence of liver metastasis (HR = 1.84; 95% CI: 1.05-2.23; P = 0.03) and MVAC chemotherapy (HR = 0.54; 95% CI: 0.35-0.83; P<0.001) were significantly correlated to survival only for UTUC, not for UCB. CONCLUSION: Our study suggests discordant oncologic outcomes and prognostic factors between metastatic UTUC and UCB after cisplatin-based chemotherapy. A prospective study is warranted to validate our results.

The Prognostic Impact of Histopathological Variants in Patients with Advanced Urothelial Carcinoma.

PURPOSE: This study investigated the prognostic role of histopathological variants in patients with advanced urothelial carcinoma (UC) who were treated with systemic chemotherapy. MATERIALS AND METHODS: We conducted a retrospective analysis of patients with unresectable and/or metastatic UC who underwent systemic chemotherapy between January 1997 and December 2013 in Kaohsiung Chang Gung Memorial Hospital. Histopathological types were categorized as pure UC (PUC) and variants of UC (VUC). The overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier analyses and Cox proportional regression models. RESULTS: A total of 206 patients were enrolled; 53 of the patients (25.7%) had histopathological variants. The most common variant was squamous differentiation (68%). Compared with patients with PUC, patients with VUC significantly exhibited upper urinary tract origin (75% vs 52%, P = .008), chronic renal insufficiency (40% vs 23%, P = .03), and carboplatin-based chemotherapy (28% vs 10%, P = .003). According to univariate analysis, the median OS for PUC patients was significantly higher than that for VUC patients (15.9 vs 11.3 months, P = .007). The median PFS for patients who received first-line chemotherapy was 6.1 and 3.8 months for PUC patients and VUC patients, respectively (P = .004). Multivariate analysis revealed that VUC (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.16-2.40, P = .006), an age ≤ 60 years (HR 0.70, 95% CI 0.49-0.99, P = .045) and presence of visceral metastasis (HR 1.54, 95% CI 1.11-2.13, P = .009) were independent factors facilitating OS prediction. CONCLUSIONS: The presence of histopathological variants indicates poor survival outcomes in patients with metastatic UC. Accordingly, VUC should be integrated into and considered an independent factor in a predictive model of survival.

Protective effects of resveratrol against UVA-induced damage in ARPE19 cells.

Ultraviolet radiation, especially UVA, can penetrate the lens, reach the retina, and induce oxidative stress to retinal pigment epithelial (RPE) cells. Even though it is weakly absorbed by protein and DNA, it may trigger the production of reactive oxygen species (ROS) and generate oxidative injury; oxidative injury to the retinal pigment epithelium has been implicated to play a contributory role in age-related macular degeneration (AMD). Studies showed that resveratrol, an abundant and active component of red grapes, can protect several cell types from oxidative stress. In this study, adult RPE cells being treated with different concentrations of resveratrol were used to evaluate the protective effect of resveratrol on RPE cells against UVA-induced damage. Cell viability assay showed that resveratrol reduced the UVA-induced decrease in RPE cell viability. Through flow cytometry analysis, we found that the generation of intracellular H2O2 induced by UVA irradiation in RPE cells could be suppressed by resveratrol in a concentration-dependent manner. Results of Western blot analysis demonstrated that resveratrol lowered the activation of UVA-induced extracellular signal-regulated kinase, c-jun-NH2 terminal kinase and p38 kinase in RPE cells. In addition, there was also a reduction in UVA-induced cyclooxygenase-2 (COX-2) expression in RPE cells pretreated with resveratrol. Our observations suggest that resveratrol is effective in preventing RPE cells from being damaged by UVA radiation, and is worth considering for further development as a chemoprotective agent for the prevention of early AMD.

Prognostic impact of renin-angiotensin system blockade in esophageal squamous cell carcinoma.

INTRODUCTION: The aim of this study is to evaluate whether the administration of renin-angiotensin system (RAS) inhibitors, angiotensin-I converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), is associated with treatment outcome in patients with esophageal squamous cell carcinoma. MATERIALS AND METHODS: A total of 141 esophageal squamous cell carcinoma patients receiving esophagectomy were identified, and were divided into two groups: an ACEI/ARB group (n=20), and a non-ACEI/ARB group (n=121). The effect of ACEIs or ARBs on cell proliferation and vascular endothelial growth factor (VEGF) secretion of esophageal squamous cell carcinoma cell lines, CE81T/VGH and TE2, were investigated by 3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Enzyme-linked immunosorbent assay (ELISA), respectively. RESULTS: Use of ACEI/ARB (p=0.032), pathologic T stage (p<0.001), pathologic N stage (p=0.012), tumor stage (p=0.006), and tumor location (p=0.032) were significantly associated with superior overall survival. In multivariate comparison, use of ACEI/ARB (p=0.006), tumor stage (p=0.002), and tumor location (p=0.014) represented the independent prognosticators of superior overall survival. In cell lines, ACEIs/ARBs inhibit cell proliferation and VEGF secretion in a dose-dependent manner. CONCLUSIONS: ACEIs/ARBs administration is independently associated with superior overall survival in patients with esophageal squamous cell carcinoma receiving esophagectomy. Our data support further investigation of the role of RAS inhibitors as a potential therapy in esophageal squamous cell carcinoma.