KCNJ3 is a new independent prognostic marker for estrogen receptor positive breast cancer patients

Numerous studies showed abnormal expression of ion channels in different cancer types. Amongst these, the potassium channel gene KCNJ3 (encoding for GIRK1 proteins) has been reported to be upregulated in tumors of patients with breast cancer and to correlate with positive lymph node status. We aimed to study KCNJ3 levels in different breast cancer subtypes using gene expression data from the TCGA, to validate our findings using RNA in situ hybridization in a validation cohort (GEO ID GSE17705), and to study the prognostic value of KCNJ3 using survival analysis. In a total of > 1000 breast cancer patients of two independent data sets we showed a) that KCNJ3 expression is upregulated in tumor tissue compared to corresponding normal tissue (p < 0.001), b) that KCNJ3 expression is associated with estrogen receptor (ER) positive tumors (p < 0.001), but that KCNJ3 expression is variable within this group, and c) that ER positive patients with high KCNJ3 levels have worse overall (p < 0.05) and disease free survival probabilities (p < 0.01), whereby KCNJ3 is an independent prognostic factor (p <0.05). In conclusion, our data suggest that patients with ER positive breast cancer might be stratified into high risk and low risk groups based on the KCNJ3 levels in the tumor

Hospitalizations and Clinical Outcome in Metastatic Colorectal Cancer During Regorafenib or TAS-102 Therapy

Current National Comprehensive Cancer Network (NCCN) and European Society of Medical Oncology (ESMO) guidelines recommend regorafenib or trifluridine/tipiracil (TAS-102) for the third-line therapy of metastatic colorectal cancer (mCRC). In this analysis, we evaluated hospitalizations during regorafenib or TAS-102 treatment and the impact of hospitalizations on overall survival (OS). This retrospective analysis was based on unselected, consecutive mCRC patients treated with regorafenib and/or TAS-102 at the tertiary cancer centers in Salzburg and Wels-Grieskirchen, Austria. Between January 2013 and May 2019, 93 patients started third- or fourth-line therapy with regorafenib or TAS-102. Tumor therapy (regorafenib versus TAS-102, HR: 1.95 [95% CI: 1.07&ndash;3.54], p = 0.03) and the Eastern Cooperative Oncology Group (ECOG) performance status (2&ndash;3 versus 0&ndash;1, HR: 4.04 [95% CI: 2.11&ndash;7.71], p &lt; 0.001) showed a statistically significant association with hospitalization risk in multivariate analysis. The corresponding hospitalization probability from initiation of third- or fourth-line was 30% with regorafenib versus 18% with TAS-102 at five weeks and 41% versus 28% at ten weeks, respectively. Hospitalizations irrespective of cause during regorafenib or TAS-102 therapy did neither impact median survival in patients undergoing only third-line therapy (never-hospitalized: 5.7 months [95% CI: 3.9&ndash;10.5] versus hospitalized: 5.4 months [95% CI: 2.8&ndash;9.6], p = 0.45), nor in patients receiving third- and fourth-line therapy (12.2 months [95% CI: 10.6&ndash;28.8] versus 18.6 months [95% CI: 6.3-not reached], p = 0.90). In conclusion, apart from poor ECOG performance status, regorafenib therapy was associated with an increased hospitalization probability during palliative systemic third- and fourth-line therapy in mCRC. However, hospitalizations during regorafenib or TAS-102 therapy did not impact OS beyond second-line therapy

Clinical Impact of RANK Signalling in Ovarian Cancer

Ovarian cancer (OC) is a gynaecological malignancy with poor clinical outcome and limited treatment options. The receptor activator of nuclear factor-&kappa;B (RANK) pathway, activated by RANK ligand (RANKL), critically controls bone metabolism, tumourigenesis and tumour immune responses. Denosumab, a monocloncal RANKL antibody, exerts tumour-suppressive effects in mice and humans. Here, we investigated the relevance of RANK signalling in OC. RANK, RANKL and OPG expression in 192 epithelial OC tissues was compared to expression in 35 non-malignant control tissues and related to clinico-pathological characteristics. Findings were validated in a cohort of 563 OC patients from The Cancer Genome Atlas (TCGA). The expression of RANK, RANKL and OPG was studied in four OC cell lines and the impact of RANK ligation or blockade on OC cell proliferation was determined. RANK, RANKL and OPG were expressed in epithelial and stromal cells in OC. RANKL expression was elevated in OC tissue, particularly in BRCA1/2 mutated tumours. High RANKL expression independently predicted reduced progression-free (PFS, p = 0.017) and overall survival (OS, p = 0.007), which could be validated in the TCGA cohort (PFS, p = 0.022; OS, p = 0.046, respectively). Expression of RANK and OPG in OC cells was induced by inflammatory cytokines IL-1&beta; and TNF&alpha;. Neither recombinant RANK ligation nor denosumab treatment affected OC cell proliferation. Our study independently links RANKL expression with poor clinical outcome in two unrelated OC cohorts. These findings implicate RANK signalling in the immunopathogenesis of OC and warrant clinical trials with denosumab in OC

Cell-Based Regeneration and Treatment of Liver Diseases

The liver, in combination with a functional biliary system, is responsible for maintaining a great number of vital body functions. However, acute and chronic liver diseases may lead to irreversible liver damage and, ultimately, liver failure. At the moment, the best curative option for patients suffering from end-stage liver disease is liver transplantation. However, the number of donor livers required by far surpasses the supply, leading to a significant organ shortage. Cellular therapies play an increasing role in the restoration of organ function and can be integrated into organ transplantation protocols. Different types and sources of stem cells are considered for this purpose, but highly specific immune cells are also the focus of attention when developing individualized therapies. In-depth knowledge of the underlying mechanisms governing cell differentiation and engraftment is crucial for clinical implementation. Additionally, novel technologies such as ex vivo machine perfusion and recent developments in tissue engineering may hold promising potential for the implementation of cell-based therapies to restore proper organ function

Medical informatics and digital health multilingual ontology (MIMO): A tool to improve international collaborations

International audienceBackground: Even if English is the leading language for international communication, it is essential to keep in mind that research runs at the local level by local teams generally communicating in their local/national language, especially in Europe among European projects.Objective: Therefore, the European Federation for Medical Informatics - Working Group on Health Informatics for Inter-regional Cooperation" has one objective: To develop a multilingual ontology focusing on Health Informatics and Digital Health as a collaboration tool that improves international and, in particular, European collaborations.Results: We have developed the Medical Informatics and Digital Health Multilingual Ontology (MIMO). Hosted on the Health Terminology/Ontology Portal (HeTOP), MIMO contains around 1,000 concepts, 460 MeSH Descriptors, 220 MeSH Concepts, and more than 300 newly created concepts. MIMO is continuously updated to comprise as recent as possible concepts and their translations in more than 30 languages. Moreover, the MIMO's development team constantly improves MIMO content and supporting information. Thus, during workshop discussions and one-on-one exchanges, the MIMO team has collected domain experts' opinions about the community's interests and suggestions for future enhancements. Moreover, MIMO will be integrated to support the annotation and categorization of research products into the HosmartAI European project involving more than 20 countries around Europe and worldwide.Conclusion: MIMO is hosted by HeTOP (Health Terminology/Ontology Portal), which integrates 100 terminologies and ontologies in 55 languages. MIMO is freely available online. MIMO is portable to other knowledge platforms as part of MIMO's main aims to facilitate communication between medical librarians, translators, and researchers as well as to support students' self-learning

Medical informatics and digital health multilingual ontology (MIMO): A tool to improve international collaborations

International audienceBackground: Even if English is the leading language for international communication, it is essential to keep in mind that research runs at the local level by local teams generally communicating in their local/national language, especially in Europe among European projects.Objective: Therefore, the European Federation for Medical Informatics - Working Group on Health Informatics for Inter-regional Cooperation" has one objective: To develop a multilingual ontology focusing on Health Informatics and Digital Health as a collaboration tool that improves international and, in particular, European collaborations.Results: We have developed the Medical Informatics and Digital Health Multilingual Ontology (MIMO). Hosted on the Health Terminology/Ontology Portal (HeTOP), MIMO contains around 1,000 concepts, 460 MeSH Descriptors, 220 MeSH Concepts, and more than 300 newly created concepts. MIMO is continuously updated to comprise as recent as possible concepts and their translations in more than 30 languages. Moreover, the MIMO's development team constantly improves MIMO content and supporting information. Thus, during workshop discussions and one-on-one exchanges, the MIMO team has collected domain experts' opinions about the community's interests and suggestions for future enhancements. Moreover, MIMO will be integrated to support the annotation and categorization of research products into the HosmartAI European project involving more than 20 countries around Europe and worldwide.Conclusion: MIMO is hosted by HeTOP (Health Terminology/Ontology Portal), which integrates 100 terminologies and ontologies in 55 languages. MIMO is freely available online. MIMO is portable to other knowledge platforms as part of MIMO's main aims to facilitate communication between medical librarians, translators, and researchers as well as to support students' self-learning