Exploratory insights from the immuno-oncology hollow fiber assay: A pilot approach bridging In Vitro and In Vivo models.

To facilitate the translation of immunotherapies from bench to bedside, predictive preclinical models are essential. We developed the in vivo immuno-oncology Hollow Fiber Assay (HFA) to bridge the gap between simpler cell-based in vitro assays and more complex mouse models for immuno-oncology drug evaluation. The assay involves co-culturing human cancer cell lines or primary patient-derived cancer cells with human immune cells inside semipermeable hollow fibers.

Hearing Outcomes After Ossiculoplasty With Bone or Titanium Prostheses-A Nationwide Register-Based Study.

Objectives: This study compares hearing outcomes of two prosthesis materials, bone and titanium, used in ossiculoplasty.

Design: This retrospective nationwide registry-based study uses data systematically collected by the Swedish Quality Registry for Ear Surgery (SwedEar).

Setting: The data were obtained from clinics in Sweden that perform ossiculoplasty.

Immuno-oncological effects of standard anticancer agents and commonly used concomitant drugs: an in vitro assessment.

Background: It has become evident in the field of oncology that the outcome of medical treatment is influenced by the combined effect exerted on both cancer- and immune cells. Therefore, we evaluated potential immunological effects of 46 standard anticancer agents and 22 commonly administered concomitant non-cancer drugs.

Methods: We utilized a miniaturized in vitro model system comprised of fluorescently labeled human colon and lung cancer cell lines grown as monocultures and co-cultured with activated peripheral blood mononuclear cells (PBMCs).

Validation of the Swedish Quality Register for Ear Surgery - SwedEar.

Background: The Swedish Quality Register for Ear Surgery (SwedEar) is a national register monitoring surgical procedures and outcomes of ear surgery to facilitate quality improvement. The value of the register is dependent on the quality of its data. SwedEar has never been validated regarding data quality or missing entries.

Phenotypic screening platform identifies statins as enhancers of immune cell-induced cancer cell death.

Background: High-throughput screening (HTS) of small molecule drug libraries has greatly facilitated the discovery of new cancer drugs. However, most phenotypic screening platforms used in the field of oncology are based solely on cancer cell populations and do not allow for the identification of immunomodulatory agents.

Methods: We developed a phenotypic screening platform based on a miniaturized co-culture system with human colorectal cancer- and immune cells, providing a model that recapitulates part of the tumor immune microenvironment (TIME) complexity while simultaneously being compatible with a simple image-based readout.

Increased levels of plasma cytokines and correlations to organ failure and 30-day mortality in critically ill Covid-19 patients.

Background: The infection caused by SARS CoV-2 has been postulated to induce a cytokine storm syndrome that results in organ failure and even death in a considerable number of patients. However, the inflammatory response in Corona virus disease-19 (Covid-19) and its potential to cause collateral organ damage has not been fully elucidated to date. This study aims to characterize the acute cytokine response in a cohort of critically ill Covid-19 patients.

Mebendazole is unique among tubulin-active drugs in activating the MEK-ERK pathway.

We recently showed that the anti-helminthic compound mebendazole (MBZ) has immunomodulating activity in monocyte/macrophage models and induces ERK signalling. In the present study we investigated whether MBZ induced ERK activation is shared by other tubulin binding agents (TBAs) and if it is observable also in other human cell types. Curated gene signatures for a panel of TBAs in the LINCS Connectivity Map (CMap) database showed a unique strong negative correlation of MBZ with MEK/ERK inhibitors indicating ERK activation also in non-haematological cell lines.

Hearing outcome after myringoplasty in Sweden: A nationwide registry-based cohort study.

Objectives: To present hearing results after successful primary myringoplasty surgeries registered in the Swedish Quality Registry for Myringoplasty and to evaluate the chance of hearing improvement and the risk of hearing loss.

Design: A retrospective nationwide cohort study based on prospectively collected registry data between 2002 and 2012.

Settings: Registry data from secondary and tertiary hospitals performing myringoplasty.

Mebendazole-induced M1 polarisation of THP-1 macrophages may involve DYRK1B inhibition.

Objective: We recently showed that the anti-helminthic compound mebendazole (MBZ) has immunomodulating activity by inducing a M2 to M1 phenotype switch in monocyte/macrophage models. In the present study we investigated the potential role of protein kinases in mediating this effect.

Results: MBZ potently binds and inhibits Dual specificity tyrosine-phosphorylation-regulated kinase 1B (DYRK1B) with a Kd and an IC of 7 and 360 nM, respectively.

Tinnitus and taste disturbances reported after myringoplasty: Data from a national quality registry.

Objectives/hypothesis: Postoperative tinnitus and taste disturbances after myringoplasty are more common than previously reported.

Study Design: This study was a retrospective analysis of prospectively collected data from the Swedish National Quality Registry for Myringoplasty.

Methods: The analysis was performed on extracted data from all counties in Sweden collected from database A from 2002 to 2012 and database B from 2013 to 2016.

Mebendazole stimulates CD14+ myeloid cells to enhance T-cell activation and tumour cell killing.

Mebendazole (MBZ) was recently shown to induce a tumor suppressive M1 phenotype in THP-1 monocytes and macrophages. In the present study the immune effects of MBZ was further investigated using human peripheral blood mononuclear cells (PBMCs) co-cultured with tumour cells. The Biomap platform was used to screen for biomarkers induced from MBZ exposed co-cultures of T-cell receptor activated PBMCs, HT29 colon cancer cells and either human fibroblasts or human umbilical vein endothelial cells (HUVEC) cells.

The anticancer effect of mebendazole may be due to M1 monocyte/macrophage activation via ERK1/2 and TLR8-dependent inflammasome activation.

Mebendazole (MBZ), a drug commonly used for helminitic infections, has recently gained substantial attention as a repositioning candidate for cancer treatment. However, the mechanism of action behind its anticancer activity remains unclear. To address this problem, we took advantage of the curated MBZ-induced gene expression signatures in the LINCS Connectivity Map (CMap) database.

Myringoplasty Outcomes From the Swedish National Quality Registry.

Objectives/hypothesis: Data from patients registered for myringoplasty during 2002 to 2012 in the Swedish National Quality Registry for Myringoplasty.

Study Design: Both conventional myringoplasty and fat-graft techniques were used aimed at healing the tympanic membrane in noninfected ears.

Methods: Analysis was performed on data in a national database collected from 32 ear, nose, and throat clinics.

Clonal Variation in Drug and Radiation Response among Glioma-Initiating Cells Is Linked to Proneural-Mesenchymal Transition.

Intratumoral heterogeneity is a hallmark of glioblastoma multiforme and thought to negatively affect treatment efficacy. Here, we establish libraries of glioma-initiating cell (GIC) clones from patient samples and find extensive molecular and phenotypic variability among clones, including a range of responses to radiation and drugs. This widespread variability was observed as a continuum of multitherapy resistance phenotypes linked to a proneural-mesenchymal shift in the transcriptome.