Background: Lung eosinophilia is a hallmark of asthma, and eosinophils are believed to play a crucial role in the pathogenesis of allergic inflammatory diseases. Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, are produced in high amounts in the gastrointestinal tract by commensal bacteria and can be absorbed into the bloodstream. Although there is recent evidence that SCFAs are beneficial in allergic asthma models, the effect on eosinophils has remained elusive. Objective: The role of SCFAs was investigated in human eosinophil function and a mouse model of allergic asthma. Methods: Eosinophils were purified from self-reported allergic or healthy donors. Migration, adhesion to the endothelium, and

The companies publishing predatory journals are an emerging problem in the area of scientific literature as they only seek to drain money from authors without providing any customer service for the authors or their readership. These predatory journals try to attract new submissions by aggressive email advertising and high acceptance rates. But in turn, they do not provide proper peer review, and therefore, the scientific quality of submitted articles is questionable. This is important because more and more people, including patients, are reading such journals and rely on the information they provide. Consequently, predatory journals are a serious threat to the integrity of medical science, and it is crucial for scientists, physicians and even patients to be aware of this problem. In this review, we briefly summarize the history of the open access movement, as well as the rise of and roles played by predatory journals. In conclusion, young and inexperienced authors publishing in a predatory journal must be aware of the damage of their reputation, of inadequate peer review processes and that unprofitable journals might get closed and all published articles in that journal might be lost.

IntroductionImmunotherapy is a well-established treatment option in patients with metastatic melanoma. However, biomarkers that can be used to predict a response in these patients have not yet been found, putting patients at risk of severe side effects.MethodsIn this retrospective analysis, we investigated the association between the body mass index and ipilimumab treatment response in patients with metastatic melanoma. Patients with metastatic melanoma who received a monotherapy of up to 4 doses of ipilimumab (3 mg/kg) every 3 weeks from 2011 to 2014 in three major hospitals in Austria were included. Patients were classified into two groups: normal group (BMI<25) and overweight group (BMI≥25).Results40 patients had a normal BMI, and 36 had a BMI above normal. Patients with a BMI that was above normal showed significantly higher response rates (p = 0.024, χ2), and lower likelihood of brain metastases (p = 0.012, χ2). No differences were found between both groups with respect to gender (p = 0.324, χ2), T-stage (p = 0.197, χ2), or the occurrence of side effects (p = 0.646, χ2). Patients with a BMI above normal showed a trend towards longer overall survival (p = 0.056, Log-Rank), but no difference was found regarding progression-free survival (p = 0.924, Log-Rank).ConclusionsThe BMI correlated with the response to ipilimumab treatment in a cohort of metastatic melanoma patients.

Biomarker-driven personalized cancer therapy is a field of growing interest, and several molecular tests have been developed to detect biomarkers that predict, e.g., response of cancers to particular therapies. Identification of these molecules and understanding their molecular mechanisms is important for cancer prognosis and the development of therapeutics for late stage diseases. In the past, significant efforts have been placed on the discovery of protein or DNA-based biomarkers while only recently the class of long non-coding RNA (lncRNA) has emerged as a new category of biomarker. The mammalian genome is pervasively transcribed yielding a vast amount of non-protein-coding RNAs including lncRNAs. Hence, these transcripts represent a rich source of information that has the potential to significantly contribute to precision medicine in the future. Importantly, many lncRNAs are differentially expressed in carcinomas and they are emerging as potent regulators of tumor progression and metastasis. Here, we will highlight prime examples of lncRNAs that serve as marker for cancer progression or therapy response and which might represent promising therapeutic targets. Furthermore, we will introduce lncRNA targeting tools and strategies, and we will discuss potential pitfalls in translating these into clinical trials.

SOX9 has been previously shown to be involved in hepatocellular carcinoma (HCC) and other types of cancer. However, prognostic studies so far involved rather small cohorts or lack external validation and experimental data. In this study, we firstly determined the histological expression pattern of SOX9 in human HCC by immunohistochemistry (n = 84) and evaluated its prognostic value. External cohorts of publicly available datasets were used to validate its prognostic relevance in HCC (n = 359) and other types of cancer including breast (n = 3951), ovarian (n = 1306), lung (n = 1926) and gastric cancer (n = 876). Functional SOX9 knock-down studies using siRNA and cancer stem cell models were generated in a panel of liver and breast cancer cell lines. High level of SOX9 was associated with poor survival even after adjustment for other prognostic factors in multivariate analysis (HR = 2.103, 95%CI = 1.064 to 4.156, p = 0.021). SOX9 prevailed a poor prognostic factor in all cancer validation cohorts (p<0.05). Reduced SOX9 expression by siRNA decreased the growth of liver cancer cells (p<0.05). SOX9 expression was associated with stem cell features in all tested cell lines (p<0.05). In conclusion, this study demonstrated in a large number of patients from multiple cohorts that high levels of SOX9 are a consistent negative prognostic factor.

Purpose Tumour diameter, tumour height, and tumour volume are considered important prognostic indicators of survival in choroidal melanomas. In this study, we investigated the prognostic impact on survival of the easily calculated volume estimate based on the assumption of a half-rotation ellipsoid. Methods The largest tumour diameter and tumour height were measured by ultrasound A-and B-scan in 93 patients with choroidal melanoma. Tumour volume was calculated by the half volume of a rotation ellipsoid formula, rotated around the y-axis, and compared to tumour diameter and tumour height. All parameters were correlated to the clinical outcome of the patients. Results At the time of diagnosis, the mean diameter was 10.4 mm (range 4.1-18.9 mm), and the mean height was 5.7 mm (range 1.74-14.9 mm). The range of the calculated tumour volume was between 11 and 628 mm 3 (mean volume 190 mm 3 ). Among all patients, distant metastases occurred in 10 patients (10.8%). In a univariate approach using Mantel-Haenszel log-rank test, the calculated tumour volume at the time of diagnosis was the best prognostic indicator of survival followed by tumour diameter and tumour height (P ¼ 0.028). When tumour volume, horizontal and vertical tumour diameter, age, sex, and primary tumour therapy were considered in a multivariate approach using Cox proportional Hazard model, only tumour volume turned out as a significant prognostic parameter (P ¼ 0.001). Conclusions Calculated tumour volume is a better prognostic indicator of survival of patients with choroidal melanomas than the largest tumour diameter and tumour height, and might be established in daily routine.

Background: PD1 inhibitors as well as PD1/CTLA4 combinations have shown remarkable efficacy in the first-line treatment of metastatic melanoma. The impact of many concomitant medications on the clinical outcomes from PD1 based therapies remains elusive. Methods: We retrospectively analyzed 140 patients included in the Checkmate 069 phase II clinical trial as a discovery cohort, comparing ipilimumab monotherapy with ipilimumab combined with nivolumab. We compared response rates, progression-free survival and overall survival of patients treated or not with 11 different classes of comedications at immune therapy initiation. Disease stage, LDH levels, BRAF status, sex, age, and body mass index were also compared. Furthermore, a protein array was performed for 440 analytes in a subset of 135 patients for whom pretreatment serum was available. We validated the impact of proton pump inhibitors in an independent cohort of 68 PD1 monotherapy (pembrolizumab or nivolumab) treated patients. Results: In univariate analysis, baseline proton pump inhibitor treatment almost halved the objective response rates, reduced progression-free and overall survival of patients treated with ipilimumab and nivolumab but not with ipilimumab alone. This effect was maintained when accounted for multiple comparisons and in a multivariate analysis. Pretreatment serum protein analysis showed increased NCAM1 and CSF3R levels in PPI users. We found increased baseline blood leukocyte and neutrophil levels in correlation with PPI use. The results were confirmed in an independent cohort of 68, first-line melanoma patients. Conclusions: Our analysis shows that proton pump inhibitors could negatively impact on the benefit from PD1 based therapies both for monotherapy and also for ipilimumab and nivolumab combination therapy. PPIs might establish a unique inflammatory immune status, prior to immune therapy initiation that interferes with treatment efficacy. These results suggest that if possible PPIs should be avoided in patients who are destined for PD1-based immunetherapies. Also, the results will have important implication for design of future clinical trials.

SummaryToday, dermatoscopy is an integral part of every clinical skin examination, as it markedly enhances the early detection of melanocytic and nonmelanocytic skin cancer (NMSC) compared to naked-eye inspection. Besides its diagnostic use, this noninvasive method is increasingly important in the selection of as well as the response assessment to various therapies used for NMSC, including basal cell carcinoma, actinic keratoses, squamous cell carcinoma, and also rare tumors such as Merkel cell carcinoma, angiosarcoma, or dermatofibrosarcoma protuberans. Thus, dermatoscopy is a valid tool for the preoperative assessment of tumor margins in basal cell carcinoma, but also for follow-up of actinic keratoses after topical treatment. The present article presents an overview on the use of dermatoscopy in the diagnosis and therapy of various types of NMSC.