Gram-negative bacteria mediated gemcitabine resistance in pre-clinical models. We determined if intratumoural lipopolysaccharide (LPS) detection by immunohistochemistry is associated with outcome in advanced pancreatic ductal adenocarcinoma (PDAC) treated with gemcitabine and non-gemcitabine containing 1st-line chemotherapy. We examined LPS on tumour tissue from 130 patients treated within the randomised AIO-PK0104 trial and a validation cohort (n = 113) and analysed the association of LPS detection to patient outcome according to treatment subgroups. In 24% of samples from the AIO-PK0104 study LPS was detected; in LPS-positive patients median OS was 4.4 months, compared to 7.3 months with LPS negative tumours (HR 1.732, p = 0.010). A difference in OS was detected in 1st-line gemcitabine-treated patients (n = 71; HR 2.377, p = 0.002), but not in the non-gemcitabine treatment subgroup (n = 59; HR 1.275, p = 0.478). Within the validation cohort, the LPS positivity rate was 23%, and LPS detection was correlated with impaired OS in the gemcitabine subgroup (n = 94; HR 1.993, p = 0.008) whereas no difference in OS was observed in the non-gemcitabine subgroup (n = 19; HR 2.596, p = 0.219). The detection of intratumoural LPS as surrogate marker for gram-negative bacterial colonisation may serve as a negative predictor for gemcitabine efficacy in advanced PDAC. The Clinical trial registry identifier is NCT00440167. The Clinical trial registry identifier is NCT00440167. Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk. Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking. For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx). Present results further encourage the reduction of alcohol intensity to mitigate HNC risk. Present results further encourage the reduction of alcohol intensity to mitigate HNC risk.Recent studies have highlighted a major role for cancer-associated fibroblasts (CAFs) in promoting immunotherapy resistance by excluding T cells from tumours. Recently, we showed that CAFs can be effectively targeted by inhibiting the enzyme NOX4; this 'normalises' CAFs and overcomes immunotherapy resistance. Here we discuss our study and other strategies for CAF targeting.This cohort study aimed to investigate the association between household income and incident hypertension in a Japanese employed population. During 2012, a total of 4314 normotensive daytime employees (3153 men and 1161 women) were included in this study. Participants had a wide range of occupations and were employed at one of 12 workplaces from various economic sectors in Japan. After a 2-year follow-up, incident hypertension was compared among groups according to household income less then 5.0, 5.0-7.9, 8.0-9.9, and ≥10.0 million Japanese yen (¥)/year. A Cox proportional hazard model was used to calculate the hazard ratio for incident hypertension in each household income group, compared with the group earning less then 5.0 million ¥/year. The hazard ratios for men were 1.52 (95% confidence interval, 1.08-2.18) for 5.0-7.9 million ¥/year, 1.49 (0.98-2.27) for 8.0-9.9 million ¥/year, and 1.92 (1.23-3.01) for ≥10.0 million ¥/year after adjusting for age, baseline systolic blood pressure, worksite, type of occupation, number of family members, and smoking status. This positive relationship was attenuated but remained significant after further adjustment for alcohol consumption and body mass index, both of which were higher among men with higher household income. Conversely, there was no significant difference for women in the risk of incident hypertension among household income groups, although those with higher household income tended to have a lower risk of incident hypertension. Household income is positively associated with the onset of hypertension in Japanese employed men working daytime hours. Obesity is an independent risk factor for coronary artery disease (CAD), but once CAD has developed it has been associated with improved survival ("obesity paradox"). To assess how obesity affects prognosis in patients with or without inducible ischemic regional wall motion abnormalities (RWMA) and/or abnormal coronary flow velocity reserve (CFVR) during stress echocardiography (SE). In an observational retrospective two- center study design, we analyzed 3249 consecutive patients (1907 men; age 66 ± 12 years; body mass index, BMI, 26.9 ± 4.1 kg/m ) with known (n = 1306) or suspected (n = 1943) CAD who underwent dipyridamole SE with simultaneous evaluation of RWMA and CFVR. All-cause death was the outcome end-point. 1075 patients were lean (BMI 18.5-24.9 kg/m ), 1523 overweight (BMI 25.0-29.9 kg/m ), and 651 obese (≥30.0 kg/m ). https://www.selleckchem.com/products/nb-598.html Ischemic test result for RWMA occurred in 28 (3%) lean, 69 (4%) overweight, and 28 (4%) obese patients (p = 0.03). An abnormal CFVR (≤2.0) was found in 281 (26%) lean, 402 (26%) overweight and 170 (26%) obese patients (p = 0.99). During 68 ± 44 months of follow-up, 496 (15%) patients died. At multivariable Cox analysis, BMI ≥ 30 was an independent predictor of reduced mortality in the 878 patients with stress-induced (≥2 segments) RWMA and/or CFVR abnormality (HR 0.58, 95% CI 0.40-0.84; p = 0.003), while showed no effect at univariate analysis in the 2371 patients with no RWMA and normal CFVR (HR 1.04, 95% CI 0.74-1.46; p = 0.84). Obesity exerts a "paradoxical" protective effect in patients with stress-induced ischemia and/ or coronary microvascular dysfunction, and shows a neutral effect in patients with normal CFVR and no stress-induced RWMA. Obesity exerts a "paradoxical" protective effect in patients with stress-induced ischemia and/ or coronary microvascular dysfunction, and shows a neutral effect in patients with normal CFVR and no stress-induced RWMA.