RNAscope 2.5 LS Assay

The distinction of atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) from its benign counterpart, lipoma, may represent a challenge. MDM2 DNA amplification is used as the gold standard as MDM2 immunohistochemistry lacks specificity and sensitivity. Herein, we investigate the diagnostic utility of MDM2 RNA in situ hybridization (RNA-ISH) and compare the test with MDM2 immunohistochemistry and MDM2 DNA fluorescence in situ hybridization (FISH) in benign and malignant lipomatous neoplasms.

The role of PD-L1 as a prognostic and predictive biomarker is an area of great interest. However, there is a lack of consensus on how to deliver PD-L1 as a clinical biomarker. At the heart of this conundrum is the subjective scoring of PD-L1 IHC in most studies to date. Current standard scoring systems involve separation of epithelial and inflammatory cells and find clinical significance in different percentages of expression, e.g., above or below 1%. Clearly, an objective, reproducible and accurate approach to PD-L1 scoring would bring a degree of necessary consistency to this landscape.

Inhibition of the PARP superfamily tankyrase enzymes suppresses Wnt/b-catenin
signalling in tumour cells. Here, we describe here a novel, drug-like small molecule
inhibitor of tankyrase MSC2504877 that inhibits the growth of APC mutant colorectal
tumour cells. Parallel siRNA and drug sensitivity screens showed that the clinical CDK4/6
inhibitor palbociclib, causes enhanced sensitivity to MSC2504877. This tankyrase
inhibitor-CDK4/6 inhibitor combinatorial effect is not limited to palbociclib and

Capable of mediating efficient transfection and protein production without eliciting innate immune responses, chemically modified mRNA holds great potential to produce paracrine factors at a physiologically beneficial level, in a spatiotemporally controlled manner, and with low toxicity. Although highly promising in cardiovascular medicine and wound healing, effects of this emerging therapeutic on the microvasculature and its bioactivity in disease settings remain poorly understood.

In situ analysis of biomarkers is essential for clinical diagnosis and research purposes. The increasing need to understand the molecular signature of pathologies has led to the blooming of ultrasensitive and multiplexable techniques that combine in situ hybridization (ISH) and immunohistochemistry or immunocytochemistry (IHC or ICC). Most protocols are tailored to formalin-fixed paraffin embedded (FFPE) tissue sections.

Abstract

BACKGROUND & AIMS:

Intestinal fibrosis is a long-term complication in inflammatory bowel diseases (IBD) frequently resulting in functional damage, bowel obstruction, and surgery. Interleukin 36 (IL36) is a group of cytokines in the IL1 family with inflammatory effects. We studied expression of IL36 and its receptor, interleukin 1 receptor like 2 (IL1RL2 or IL36R) in development of intestinal fibrosis in human tissues and mice.

METHODS:

Abstract

PURPOSE:

Ocular adnexal (OA) sebaceous carcinoma is an aggressive malignancy of the eyelid and ocular adnexa that frequently recurs and metastasizes, and effective therapies beyond surgical excision are lacking. There remains a critical need to define the molecular-genetic drivers of the disease to understand carcinomagenesis and progression and to devise novel treatment strategies.

EXPERIMENTAL DESIGN:

Sensory hair cells located in the organ of Corti are essential for cochlear mechanosensation. Their loss is irreversible in humans resulting in permanent hearing loss. The development of therapeutic interventions for hearing loss requires fundamental knowledge about similarities and potential differences between animal models and human development as well as the establishment of human cell based-assays. Here we analyze gene and protein expression of the developing human inner ear in a temporal window spanning from week 8 to 12 post conception, when cochlear hair cells become specified.

The gut microbiota is strongly influenced by environmental factors, although host contribution is far less understood. We leveraged macrophage-deficient interferon regulatory factor irf8 zebrafish mutants to investigate the role of macrophages in this process. In conventionally raised adult irf8-deficient mutants, we found a significant loss of intestinal macrophages associated with a strikingly altered gut microbiota when compared to co-housed siblings.

Strong human genetic evidence points to an essential contribution of the voltage-gated sodium channel Nav1.7 to pain sensation: loss of Nav1.7 function leads to congenital insensitivity to pain, while gain-of-function mutations in the SCN9A gene that encodes Nav1.7 cause painful neuropathies such as inherited erythromelalgia, a syndrome characterized by episodic spontaneous pain. Selective Nav1.7 channel blockers thus hold promise as potential painkillers with improved safety and reduced unwanted side effects compared to existing therapeutics.