Yen Kuang Lin

Pterostilbene suppressed irradiation-resistant glioma stem cells by modulating GRP78/miR-205 axis

Glioblastoma multiforme (GBM) is the most aggressive type characterized by relapse and resistance even with the combination of radio- and chemotherapy. The presence of glioma stem cells (GSCs) has been shown to contribute to tumorigenesis, recurrence and treatment resistance. Particularly, CD133-positive glioma cells have been shown to represent the subpopulation that confers glioma radioresistance and suggested to be the source of tumor recurrence after radiation. Thus, a better understanding and the development of agents which target GSCs could potentially lead to a significant improvement in treating GBM patients. Here, we demonstrated that GRP78 (an antistress protein) was highly expressed in GBM cells along with β-catenin and Notch and correlated to the development of GSCs. CD133+ GSCs exhibited enhanced migration/invasion and self-renewal abilities. When GRP78 was silenced, GSC properties were suppressed and the sensitivity towards irradiation increased. In addition, the level of microRNA 205 appeared to be negatively associated with GRP78 expression. Our previous study indicated that pterostilbene (PT) possessed anticancer stem cell properties in hepatocellular carcinoma. Thus, we examined whether PT is also effective against GSCs. We found that PT-treated GSCs exhibited suppressed self-renewal and irradiation-resistant abilities. PT-mediated effects were associated with an increase of miR-205. Finally, we showed that PT treatment suppressed tumorigenesis in GSC xenograft mice. In conclusion, we provided evidence that GRP78/miR-205 axis played an important role in GSC maintenance and irradiation resistance. PT treatment suppressed GSC development via negatively modulating GRP78 signaling. PT may be considered for combined therapeutic agent to enhance irradiation efficacy in GBM patients.

Improvement of Fecal Incontinence and Quality of Life by Electrical Stimulation and Biofeedback for Patients With Low Rectal Cancer After Intersphincteric Resection

OBJECTIVE To assess the efficacy and benefits of pelvic rehabilitation programs in terms of functional outcomes and quality of life for patients with fecal incontinence and defecation disorders after rectal cancer surgery. DESIGN Prospective, observational study. SETTING University hospital physiotherapy clinics. PARTICIPANTS Patients (N=32) who experienced fecal incontinence after sphincter-saving surgery with the intersphincteric resection (ISR) technique and could follow and cooperate with the treatment schedule were included in the present study. INTERVENTIONS Pelvic rehabilitation programs included electrical stimulation (ES) and biofeedback (BF). MAIN OUTCOME MEASURES Functional results, Wexner score, and anorectal manometry were used to assess the clinical outcomes of rehabilitation treatment. RESULTS Maximum squeeze pressure improved after rehabilitation training (P=.014). There were no statistical differences in resting pressure, resting muscle electromyography, and maximum squeeze electromyography (P=.061, P=.76, and P=.99, respectively). The mean stool frequency was 18.8 per 24 hours before the pelvic intervention program and 7.8 per 24 hours after ES and BF training (P<.001). Of the 32 patients, 27 required antidiarrheal medications before treatment, and after completion of the training, only 9 patients still needed antidiarrheal medications (P<.001). Significant improvements were observed in the Wexner score (17.74 vs 12.93; P<.001). CONCLUSIONS Our data show that ES and BF are effective in the treatment of fecal incontinence, leading to improvement of quality of life for patients with low rectal cancer after ISR.

Antiseptic Effect of Conventional Povidone-Iodine Scrub, Chlorhexidine Scrub, and Waterless Hand Rub in a Surgical Room: A Randomized Controlled Trial

OBJECTIVE Effective perioperative hand antisepsis is crucial for the safety of patients and medical staff in surgical rooms. The antimicrobial effectiveness of different antiseptic methods, including conventional hand scrubs and waterless hand rubs, has not been well evaluated. DESIGN, SETTING, AND PARTICIPANTS A randomized controlled trial was conducted to investigate the effectiveness of the 3 antiseptic methods among surgical staff of Taipei Medical University-Shuang Ho Hospital. For each method used, a group of 80 participants was enrolled. INTERVENTION Surgical hand cleansing with conventional 10% povidone-iodine scrub, conventional 4% chlorhexidine scrub, or waterless hand rub (1% chlorhexidine gluconate and 61% ethyl alcohol). RESULTS Colony-forming unit (CFU) counts were collected using the hand imprinting method before and after disinfection and after surgery. After surgical hand disinfection, the mean CFU counts of the conventional chlorhexidine (0.5±0.2, P<0.01) and waterless hand rub groups (1.4±0.7, P<0.05) were significantly lower than that of the conventional povidone group (4.3±1.3). No significant difference was observed in the mean CFU count among the groups after surgery. Similar results were obtained when preexisting differences before disinfection were considered in the analysis of covariance. Furthermore, multivariate regression indicated that the antiseptic method (P=.0036), but not other variables, predicted the mean CFU count. CONCLUSIONS Conventional chlorhexidine scrub and waterless hand rub were superior to a conventional povidone-iodine product in bacterial inhibition. We recommend using conventional chlorhexidine scrub as a standard method for perioperative hand antisepsis. Waterless hand rub may be used if the higher cost is affordable. Infect Control Hosp Epidemiol 2017;38:417-422.

4-Acetylantroquinonol B suppresses autophagic flux and improves cisplatin sensitivity in highly aggressive epithelial cancer through the PI3K/Akt/mTOR/p70S6K signaling pathway

ABSTRACT Targeting residual self‐renewing, chemoresistant cancerous cells may represent the key to overcoming therapy resistance. The entry of these quiescent cells into an activated state is associated with high metabolic demand and autophagic flux. Therefore, modulating the autophagy pathway in aggressive carcinomas may be beneficial as a therapeutic modality. In this study, we evaluated the anti‐tumor activities of 4‐acetylantroquinonol B (4‐AAQB) in chemoresistant ovarian cancer cells, particularly its ability to modulate autophagy through autophagy‐related genes (Atg). Atg‐5 was overexpressed in invasive ovarian cancer cell lines and tissue (OR: 5.133; P = 0.027) and depleting Atg‐5 in ES‐2 cell lines significantly induced apoptosis. 4‐AAQB effectively suppressed viability of various subtypes of ovarian cancer. Cells with higher cisplatin‐resistance were more responsive to 4‐AAQB. For the first time, we demonstrate that 4‐AAQB significantly suppress Atg‐5 and Atg‐7 expression with decreased autophagic flux in ovarian cancer cells via inhibition of the PI3K/Akt/mTOR/p70S6K signaling pathway. Similar to Atg‐5 silencing, 4‐AAQB‐induced autophagy inhibition significantly enhanced cell death in vitro. These results are comparable to those of hydroxychloroquine (HCQ). In addition, 4‐AAQB/cisplatin synergistically induced apoptosis in ovarian cancer cells. In vivo, 4‐AAQB/cisplatin also significantly induced apoptosis and autophagy in an ES‐2 mouse xenografts model. This is the first report demonstrating the efficacy of 4‐AAQB alone or in combination with cisplatin on the suppression of ovarian cancer via Atg‐5‐dependent autophagy. We believe these findings will be beneficial in the development of a novel anti‐ovarian cancer therapeutic strategy. HIGHLIGHTSAtg‐5 is overexpressed in ovarian cancer and silencing Atg‐5 induces apoptosis.4‐AAQB suppresses autophagy and PI3K/Akt/mTOR pathway.4‐AAQB + cisplatin synergistically suppresses ovarian cancer via autophagy.

Outcomes of adjuvant treatments for resectable intrahepatic cholangiocarcinoma: Chemotherapy alone, sequential chemoradiotherapy, or concurrent chemoradiotherapy

BACKGROUND Prospective randomized trials have not been used to evaluate the efficacy of adjuvant therapies after intrahepatic cholangiocarcinoma (ICC) resection. METHODS We analyzed data from the Taiwan Cancer Registry database of ICC patients receiving resection. To compare outcomes, patients with ICC were enrolled and categorized into the following adjuvant treatment modality groups: group 1, concurrent chemoradiotherapy (CCRT); group 2, sequential chemotherapy (CT) and radiotherapy (RT); and group 3, CT alone. RESULTS We enrolled 599 patients with resectable ICC who received surgery without distant metastasis. Of these patients, 174 received adjuvant CCRT (group 1), 146 received adjuvant sequential CT and RT (group 2), and 279 received adjuvant CT alone (group 3). Multivariate Cox regression analysis indicated that pathologic stage and positive margin were significantly poor independent predictors. After adjustment for confounders, adjusted hazard ratios (95% confidence intervals) for overall mortality at advanced pathologic stages III and IV were 0.55 (0.41-0.74) and 0.92 (0.70-1.33) in groups 1 and 2, respectively, compared with group 3. CONCLUSIONS Adjuvant CCRT improved survival in resected ICC with advanced pathologic stages or a positive margin in early pathologic stages compared with adjuvant CT alone or adjuvant sequential CT and RT.

The gap between currently available evidence and awareness in clinical practice of wound care: It is the time to shower earlier

Background: A postoperative water‐forbidden strategy has been used for many decades. However, evidence shows that early contact with water postoperatively does not increase the infection rate. Our study evaluated the gap between currently available evidence and awareness in clinical practice of postoperative wound care. Methods: We conducted a systematic review to compare the outcomes between postoperative water‐contact and water‐forbidden groups. PubMed, EMBASE, and Cochrane databases were searched. A meta‐analysis was conducted to calculate a pooled effect size by using random‐effects models. On the basis of pooling results, a questionnaire survey was conducted to evaluate the gap from systematic review to clinical practice by clinical staff and patients. Results: We reviewed 12 trials including 4,086 patients. Incidence of infection and wound complications did not differ significantly between water‐contact and water‐forbidden groups. Satisfaction was significantly higher in water‐contact group than in water‐forbidden group (risk ratio: 17.33; 95% confidence interval, 11.11–27.03). A survey of clinicians showed that awareness, acceptance of the evidence, and the current water‐contact strategy differed among departments. However, many clinicians showed no willingness to apply the water‐contact strategy for various reasons. A survey of patients showed low awareness of the issue and variety in willingness to contact water. Conclusion: Water‐forbidden strategy causes inconvenience to patients. However, a majority of patients and clinicians still hesitated to apply the early water‐contact strategy, even after viewing the results of the current review. Establishment of local clinical practice guidelines, advocacy from authorities, and promotion by social media for this strategy are warranted.

Intensity-modulated radiotherapy with systemic chemotherapy improves survival in patients with nonmetastatic unresectable pancreatic adenocarcinoma: A propensity score-matched, nationwide, population-based cohort study

PURPOSE In the era of intensity-modulation radiation therapy (IMRT), no prospective randomized trial has evaluated the efficacy of IMRT exclusively, such as concurrent chemoradiotherapy (CCRT), sequential induction chemotherapy followed by radiotherapy (CT-RT), and systemic chemotherapy (CT) alone, for treating unresectable pancreatic adenocarcinomas (PAs) without metastasis. Through propensity score matching, we designed a nationwide, population-based, head-to-head cohort study to determine the effects of various treatments on unresectable PAs. PATIENTS AND METHODS We minimized the confounding effects of various treatment outcomes in patients with unresectable PAs from the Taiwan Cancer Registry database by dividing them as follows: group 1, CCRT; group 2, sequential CT-RT; group 3, nontreatment; and group 4, CT alone. RESULTS The matching process yielded a final cohort of 2960 patients (740 patients each in groups 1, 2, 3, and 4). In both univariate and multivariate Cox regression analyses, the adjusted hazard ratios (95% confidence interval) derived for the definitive CCRT and sequential CT-RT groups compared with the CT alone group were 0.443 (0.397-0.495) and 0.633 (0.568-0.705), respectively. CONCLUSIONS A combination of IMRT and systemic CT for the treatment of unresectable PAs might increase survival compared with CT alone.

Psychometric Evaluation of the Vietnamese Hemodialysis Stressor Scale

The lack of a suitable assessment tool may limit optimal stress management and impair the health-related quality of life of patients undergoing hemodialysis. The purpose of the study was to examine latent constructs and psychometric properties of the Vietnamese Hemodialysis Stressor Scale (HSS-V). In total, 180 patients receiving hemodialysis were recruited. Psychometric properties of the HSS-V, including the construct validity, internal consistency, and test–retest reliability, were tested after the instrument translation. The exploratory factor analysis resulted in a 24-item HSS-V with four extracted factors, which explained 58.32% of the total variance. The construct validity was confirmed by significant negative correlations between scores on the HSS-V and Vietnamese-version Short Form-36. The internal consistency (Cronbach’s α = .82-.91) and test–retest reliability (intra-class correlations coefficient = .91-.94) of the 24-item HSS-V were satisfactory. A simple structure and preliminary acceptable psychometric properties of the HSS-V were established and can serve as a basis for further studies.

Original Research: Physical Activity among Chinese American Immigrants with Prediabetes or Type 2 Diabetes

&NA; Background: Although the benefits of aerobic exercise and strength training for patients with type 2 diabetes have been studied extensively, research on physical activity among Chinese American immigrants diagnosed with prediabetes or type 2 diabetes has been limited. Purpose: We sought to learn more about this populations knowledge of physical activity, the types and intensity levels performed, and the barriers to such activity. Design and methods: A concurrent mixed-methods design was used. The short version of the International Physical Activity Questionnaire–Chinese was used to quantitatively measure participants’ levels of exercise intensity. Semistructured face-to-face interviews were conducted to obtain qualitative information regarding participants’ knowledge about physical activity, the types performed, and the barriers to such activity. Results: A total of 100 Chinese American immigrants were recruited for the study from January to July 2012 in New York City. On average, participants had lived with a diagnosis of prediabetes or type 2 diabetes for 3.3 years and had lived in the United States for 21.5 years. Energy expenditure was measured in metabolic equivalent of task (MET) units; intensity was measured in cumulative MET-minutes per week. The mean total intensity score was 2,744 MET-minutes per week. This was achieved mainly through walking. The mean intensity score for walking was 1,454 MET-minutes per week; the mean duration was 79 minutes per day. Vigorous physical activity was least common. The mean intensity score for vigorous physical activity was 399 MET-minutes per week, and the mean duration was 17 minutes per week. Regarding types of physical activity, the most common were housekeeping, walking up stairs, and taking walking or stretching breaks every hour during the workday. Based on the interviews, three themes emerged regarding barriers to moderate or vigorous physical activity: insufficient education about physical activity, health concerns about physical activity, and work-related barriers to physical activity. Conclusions: The majority of Chinese American immigrants with prediabetes or type 2 diabetes do not engage in sufficient physical activity, performing at a rate significantly below that of the general U.S. population. Increases in the intensity and duration of physical activity should be promoted as part of diabetes management for Chinese American immigrants.

Dysregulation of glucose metabolism since young adulthood increases the risk of cardiovascular diseases in patients with bipolar disorder

Aging patients with bipolar disorder (BD) are at a high risk of cardiovascular diseases (CVDs). However, few studies have directly examined the association between metabolic risks and CVDs in patients with BD across the lifespan. Therefore, the aim of this study was to determine lifetime metabolic risk factors for CVDs in patients with BD. We recruited BD‐I patients who were more than 50 years old and had had at least one psychiatric hospitalization. Patients who had a cardiologist‐confirmed CVD diagnosis (ICD‐9 code 401–414) were assigned to the case group. Fifty‐five cases were matched with 55 control patient without CVDs based on age and sex. Clinical data were obtained by retrospectively reviewing 30 years of hospital records. Compared to control subjects, a significantly higher proportion of cases had impaired fasting glucose between ages 31 and 40 (44.0% versus 17.4%, p = 0.046), diabetes mellitus between ages 41 and 50 (25.6% versus 8.6%, p = 0.054), and diabetes mellitus after age 51 (36.3% versus 12.7%, p = 0.005). No significant difference was found in overweight, obesity, or dyslipidemia. After adjusting for years of education, first episode as mania, and second generation antipsychotic use, lifetime diabetes mellitus remained a risk factor for CVDs (OR = 4.45, 95% CI = 1.89–10.66, p = 0.001). The findings suggest that glucose dysregulation across the adult age span is probably the major metabolic risk contributing to CVDs in patients with BD. Clinicians therefore have to notice the serum fasting glucose levels of BD patients since young adulthood.