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Background/aim The present study aimed at evaluating the contribution of IL-4 promoter T-1099G (rs2243248), C-589T (rs2243250), C-33T (rs2070874) genotypes to the risk of breast cancer in Taiwanese. Materials and methods A total of 1232 breast cancer patients and 1232 age-matched controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Results Genotypic frequencies of IL-4 rs2243248, rs2243250 and rs2070874 were not differentially distributed between case and control groups. Consistently, there was no difference in the distribution of allelic frequencies among patients and controls. Conclusion IL-4 rs2243248, rs2243250 and rs2070874 do not confer breast cancer susceptibility in Taiwanese.

Background/aim Etomidate, an intravenous anesthetic, has been shown to have anticancer effects, including induction of cell-cycle arrest and apoptosis. However, to our knowledge, there are no reports about the anti-metastasis effects of etomidate on A549 human lung adenocarcinoma cells. Materials and methods The cell viability, cell adhesion, gelatin zymography assay, transwell migration and invasion assay, and western blotting analysis were used to investigate the effects of etomidate on A549 cells. Results In our study, etomidate showed low cytotoxicity, inhibited cell adhesion, and suppressed the migration and invasion in A549 cells. The activity of matrix metallopeptidase 2 (MMP2) was reduced by 48 h treatment of etomidate. Results of western blotting analysis indicated that etomidate down-regulated the expression of protein kinase C, MMP7, MMP1, MMP9, and p-p-38, but up-regulated that of RAS, phosphoinositide 3-kinase, and phosphor-extracellular-signal related kinase after 24 and 48 h treatment, in A549 cells. Conclusion Etomidate suppressed the migration and invasion of lung adenocarcinoma A549 cells via inhibiting the expression of MMP1, MMP2, MMP7 and MMP9, and provides potential therapeutic targets for lung cancer treatment.

Background This study aimed to investigate skin condition, quality of life, and psychological impact of breast cancer patients after radiation therapy. We designed and administered a questionnaire to breast cancer survivors for better understanding the skin sequelae after radiation therapy. Methods This study performed an anonymous online survey. Invitation join was posted in Facebook groups for Breast Cancer. Content of the questionnaire included basic information and a three-point scale on the degree of skin dryness, sweating, hotness sensation, itchy sensation, presence of pigment deposition, history of severe skin disorder, psychological impact, and quality of life after radiotherapy. Categorical variables were summarized using counts and percentages, and then Mantel–Haenszel chi-square tests, multiple correspondence analysis, Wald chi-square statistics, and logistic regression analyses were performed; P Results In total, 421 breast cancer survivors completed the questionnaire. Among them, 331 (78.62%) reported rarely sweating; 340 (80.76%) reported dry skin; 184 (43.71%) reported itchy skin in addition to dry skin; 336 (79.81%) had severe or mild skin color deposition; and 76 (18.05%) had eczema or contact dermatitis. Dry skin problems were caused by absent sweating and skin dryness in the irradiated skin area, post-RT severe skin disorders, and skin color deposition. Compared with patients sweating normally in the radiation field, patients with absent sweating and hotness sensation in the radiation field had a higher risk of depression. Conclusions This study showed that breast cancer patients after whole breast radiotherapy may experience skin dryness, hypersensitivity and hyper pigmentation in the irradiated skin area. These “radiation-irritated skin” lesions may induce depressive psychological status and impact the quality of life in breast cancer patients after whole breast radiotherapy.

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BackgroundThere are emerging but inconsistent evidences about anti-epileptic drugs (AEDs) as radiosensitizers to improve survival in glioblastoma (GBM) patients. We conducted a population-based study to evaluate the impact of concurrent AED during post-operative chemo-radiotherapy (CCRT) on outcome.Methods1057 GBM patients were identified by National Health Insurance Research Database and Cancer Registry in 2008-2015. Eligible criteria included those receiving surgery, adjuvant RT and temozolomide (TMZ), and without other cancer diagnoses. Survival between patients taking concurrent AED for 14 days or more during CCRT (AED group) and those who did not (non-AED group) were compared, and subgroup analyses for valproic acid (VPA), levetiracetam (LEV), and phenytoin were performed. Multivariate analyses were used to adjust for confounding factors. ResultsThere were 642 patients in the AED group while 415 in the non-AED group. The demographic data was balanced except trend of more patients in the AED group had previous drug history of AEDs. (22.6% vs 18%, p=0.078). Overall, the AED group had significantly increased risk of mortality (HR=1.18, p=0.016). In subgroup analyses, the significant detrimental effect was demonstrated in VPA (HR=1.29, p=0.0002), but not in LEV (HR=1.18, p=0.079) and phenytoin (HR = 0.98, p=0.862). When stratified by sex and age, this detrimental effect was seen in male and patients less than 65 years old in the VPA group.Conclusion:Survival was not improved and even worse in patients with AEDs during CCRT in this nationwide population-based study. Our real-world data did not support prophylactic use of AEDs for GBM.

Purpose/Objective(s) Whole breast radiotherapy after breast-conserving surgery reduces the risk of recurrence and death and is widely used as standard treatment for breast cancer. Radiation-irritated skin, defined as “post-radiotherapy pruritic dry skin easily irritated by external stimulation, such as seasonal change or topical products”, affects quality of life of breast cancer survivors undergoing whole breast radiotherapy. FR-101 dressing is a novel dressing combined with biocellulose membrane and repair peptides to repair the damaged skin after radiotherapy. This study is aimed to test the safety and efficacy to alleviate radiation-irritated skin symptoms. Materials/Methods The study was a single-arm, open label, single center pilot clinical study to evaluate the safety and clinical outcome of the FR-Mask intervention in breast cancer patients after WBRT. Patients who complete the post-operative radiotherapy and meet the inclusion and exclusion criteria had been enrolled into the study after the study team obtains their informed consent. Each subject had received 12 packages of FR-Mask (1 mask in each individual package) and be instructed to put the patch on the irritated-skin area caused by radiation for 20 minutes every 3 days. Subjects came back to clinics for evaluation every 4 weeks for 4 months, and received physical examination and investigations including questionnaires, skin observer measurement, and taking pictures. The total study duration for each subject took 4.5 months. This study had been conducted in China Medical University Hospital. Results A total of 10 subjects were enrolled, and all subjects applied FR-101 dressing. No one experienced adverse events during the study period. Efficacy evaluation revealed that 40% patients showed visible differences between the affected breast skin and the healthy breast skin. FR-101 dressing application may increase moisture and oil level of the affected breast skin, P = 0.08 and P = 0.01, respectively. Results of comparisons between the affected breast skin and the healthy breast skin showed a trend to improve breast sensitivity. (P = 0.08) Conclusion Our findings demonstrate FR-101 dressing is a novel, safe, and feasible dressing for breast cancer patients undergoing whole breast radiotherapy. This pilot study also suggests that FR-101 dressing may promote the repair of the damaged skin appendages after radiotherapy and alleviate their radiation-irritated skin symptoms.

Lung cancer has a very high prevalence of brain metastasis, which results in a poor clinical outcome. Up-regulation of a disintegrin and metalloproteinase 9 (ADAM9) in lung cancer cells is correlated with metastasis to the brain. However, the molecular mechanism underlying this correlation remains to be elucidated. Since angiogenesis is an essential step for brain metastasis, microarray experiments were used to explore ADAM9-regulated genes that function in vascular remodeling. The results showed that the expression levels of vascular endothelial growth factor A (VEGFA), angiopoietin-2 (ANGPT2), and tissue plasminogen activator (PLAT) were suppressed in ADAM9-silenced cells, which in turn leads to decreases in angiogenesis, vascular remodeling, and tumor growth in vivo. Furthermore, simultaneous high expression of ADAM9 and VEGFA or of ADAM9 and ANGPT2 was correlated with poor prognosis in a clinical dataset. These findings suggest that ADAM9 promotes tumorigenesis through vascular remodeling, particularly by increasing the function of VEGFA, ANGPT2, and PLAT.

Various sedative agents, including dexmedetomidine (dex), induce immunosuppression, and enhance infection progression. However, there was no information on how anesthetic affects local and systemic cellular immune function. We conducted this study to examine the impact of dex on the differentiation and function of immune cells at site of inflammation and in peripheral blood during endotoxemia of mice. In BALB/c mice with and without endotoxemia, we evaluated the influence of two dosages of 5 and 50 mcg/kg/h intravenous dex on immune cells: including number of T cells (CD3), B cells (CD19), natural killer cells (CD8a), monocytes (CD11b), and macrophages (Mac-3) in peripheral blood, the activities of macrophages in peripheral blood and in peritoneal lavage, and proliferation of B and T cells and of natural killer cells activity in the spleen. Endotoxemia increased the number of CD3 T cells, CD 19 B cells and macrophages in the peripheral blood, augmented macrophage activity in the peritoneum, and increased T cell proliferation and natural killer cell activity in the spleen. Further administration of 5 mcg/kg/h dex attenuated systemic increase in number of T cells, B cells, and macrophages during endotoxemia and 50 mcg/kg/h dex significantly attenuated the increase in activity of macrophages in the peripheral blood during endotoxemia. In the peritoneum, however, 5 mcg/kg/h dex preserved and 50 mcg/kg/h dexmedetomidine enhanced the activity of macrophages during endotoxemia. Increased in proliferation of T cells in spleen during endotoxemia was attenuated by both doses of dex. Last, 50 mcg/kg/h dex enhanced natural killer cells activity during endotoxemia. While preserving the effects of endotoxemia on macrophage's activity in the infection site and natural killer cell's activity in the spleen, dex decreased systemic fulminant immune reaction in endotoxemia, by attenuating the augmented response in the number of T cells, B cells and macrophages, activity of macrophages in the peripheral blood, and proliferation of T cells in spleen during endotoxemia.

ent-13-Hydroxykaur-16-ene-19-N-butylureide (6) was one of 33 synthesized C-4-substituted steviol derivatives that were evaluated for their effects on hepatitis B virus (HBV) surface antigen (HBsAg) secretion. The IC50 (16.9 μM) and SI (57.7) values for inhibiting HBV DNA replication of compound 6 were greater than those of the reference compound, lamivudine (3-TC; IC50: 107.5 μM; SI: 22.0). Thus, the anti-HBV mechanism of 6 was investigated, and it specifically inhibited viral gene expression and reduced viral DNA levels, as well as potently attenuated all of the viral promoter activity of HBV-expressing Huh7 cells. Examination of cellular signaling pathways found that 6 inhibited the activities of the nuclear factor (NF)-κB- and activator protein (AP)-1 element-containing promoters, but had no effects on AP-2 or interferon-stimulated response element (ISRE)-containing promoters in HBV-expressing cells. Meanwhile, it significantly eliminated NF-κB and extracellular signal-regulated kinase (ERK)/mitogen-ac...

Background: This study investigated the stroke risk in patients with head and neck cancers (HNCs) using population-based data. Methods: From claims collected in the Taiwan National Health Insurance database, we identified 13 390 HNC patients with diagnosis made in 2000–2002. A reference cohort of 53 517 non-cancer individuals matched for age, gender, and stroke risk factors was used for assessing stroke risk in follow-up to 2008. Results: The overall stroke incidence was 1.44-fold higher in the HNC than in the reference cohort (11.4 vs 7.9 per 1000 person-years). Adjusted hazard ratios (HRs) were 1.54 (95% confidence interval (CI): 1.40–1.68) for ischaemic stroke and 1.36 (95% CI: 1.09–1.69) for haemorrhagic stroke. The cancer-to-reference stroke incidence rate ratio was age dependent and the highest in the age group younger than 40 years (5.45, 95% CI: 3.78–7.87) and decreased with aging. Comparing different therapeutic modalities, HNC patients receiving both radiotherapy (RT) and chemotherapy (CT) had the highest stroke risk (HR: 1.46, 95% CI: 1.22–1.74), followed in sequence by those who had CT alone, RT alone, and without therapy. Conclusion: Patients with HNC are at increased risk of developing stroke, especially in the young age group and in those who received both RT and CT.

Various sedative agents, including dexmedetomidine (dex), induce immunosuppression, and enhance infection progression. However, there was no information on how anesthetic affects local and systemic cellular immune function. We conducted this study to examine the impact of dex on the differentiation and function of immune cells at site of inflammation and in peripheral blood during endotoxemia of mice. In BALB/c mice with and without endotoxemia, we evaluated the influence of two dosages of 5 and 50 mcg/kg/h intravenous dex on immune cells: including number of T cells (CD3), B cells (CD19), natural killer cells (CD8a), monocytes (CD11b), and macrophages (Mac-3) in peripheral blood, the activities of macrophages in peripheral blood and in peritoneal lavage, and proliferation of B and T cells and of natural killer cells activity in the spleen. Endotoxemia increased the number of CD3 T cells, CD 19 B cells and macrophages in the peripheral blood, augmented macrophage activity in the peritoneum, and increased T cell proliferation and natural killer cell activity in the spleen. Further administration of 5 mcg/kg/h dex attenuated systemic increase in number of T cells, B cells, and macrophages during endotoxemia and 50 mcg/kg/h dex significantly attenuated the increase in activity of macrophages in the peripheral blood during endotoxemia. In the peritoneum, however, 5 mcg/kg/h dex preserved and 50 mcg/kg/h dexmedetomidine enhanced the activity of macrophages during endotoxemia. Increased in proliferation of T cells in spleen during endotoxemia was attenuated by both doses of dex. Last, 50 mcg/kg/h dex enhanced natural killer cells activity during endotoxemia. While preserving the effects of endotoxemia on macrophage's activity in the infection site and natural killer cell's activity in the spleen, dex decreased systemic fulminant immune reaction in endotoxemia, by attenuating the augmented response in the number of T cells, B cells and macrophages, activity of macrophages in the peripheral blood, and proliferation of T cells in spleen during endotoxemia.

Objectives This population-based cohort study investigated the ischaemic stroke risk of patients with nasopharyngeal carcinoma (NPC) by treatment. Design Controlled cohort study. Setting Based on claims data of National Health Research Insurance Database in years 1996–2010. Participants A total of 4615 patients with nasopharyngeal carcinoma newly diagnosed in 2000–2003 were divided into three subgroups: patients received radiotherapy only, patients received both radiotherapy/chemotherapy and patients received neither radiotherapy nor chemotherapy (non-radio/chemotherapy). They were compared with 36 919 reference persons without stroke and cancer, frequency matched with demographic characteristics. Main outcome measures Study subjects were followed up until 2010 to measure ischaemic stroke incidences. Risks associated with treatment and comorbidity were evaluated using Cox proportional hazards regression analysis incorporated with the competing risk of deaths. Results Ischaemic stroke incidence rates were ≈2-fold higher in nasopharyngeal carcinoma patients with radiotherapy, radiotherapy/chemotherapy and non-radio/chemotherapy than in references (13.8, 12.8 and 12.6 versus 6.07 per 1000 person-years, respectively). The risk was much higher for 20- to 39-year-old nasopharyngeal carcinoma patients with radiotherapy/chemotherapy [hazard ratio (HR) 14.7, 95% confidence interval 9.24–23.4]. Hypertension, diabetes, hyperlipidaemia and alcoholism also enhanced the risk with hazard ratios ranging from 2.4 to 9.3. The overall adjusted ischaemic stroke risk was higher in nasopharyngeal carcinoma patients with the two types of treatment than those without, but not significant. Conclusions Patients with nasopharyngeal carcinoma are at an elevated risk of ischaemic stroke, without significant difference among treatment modalities. The relative risk is more prominent in younger patients. Comorbidity may enhance the risk.

Background This study investigated the incidence and patient- and treatment-related risk factors related to pneumonia acquired during radiotherapy (PNRT) in head and neck cancer (HNC) patients. Methods Using the universal insurance claims data, 15,894 total HNC patients between 1998 and 2007 were included in this analysis. PNRT was defined as the occurrence of pneumonia within 90 days of the commencement of radiotherapy. Information also included some demographic characteristics, treatment-related factors, and comorbidities. Appropriate statistical tests were performed to assess the difference between patients with and those without PNRT. A logistic regression was used to estimate the odds ratio (OR) of PNRT among the variables examined. Results In total, 772 patients (4.86%) were identified with PNRT as the case group, whereas 15,122 subjects of the same cancer without PNRT formed the control group. Of patients with PNRT, 632 (81.9%) were hospitalized with a mean length of stay of 25.9 days. Results from the multiple logistic regression showed that an older age and certain comorbidities were associated with an increased risk of PNRT. Patients with cancer of the tongue, buccal mucosa, oropharynx, and hypopharynx/larynx were at particularly higher risk (OR = 1.28, 1.28, 1.67, and 1.74, respectively). Compared to radiotherapy alone, concurrent chemoradiotherapy had no effect on the PNRT. Patients in the PNRT group had higher overall medical costs and length of stay. Conclusion The incidence of PNRT in HNC patients receiving radiotherapy was approximately 5%. Notably, an older age, certain comorbidities, and certain specific tumor sites were associated with an increased risk.