Publications

Recent strategies targeting the interaction of the programmed cell death ligand-1 (PD-L1, B7-H1, CD274) with its receptor, PD-1, resulted in promising activity in early phase clinical trials. In this study, we used various antibodies and in situ mRNA hybridization to measure PD-L1 in non-small cell lung cancer (NSCLC) using a quantitative fluorescence (QIF) approach to determine the frequency of expression and prognostic value in two independent populations.

PURPOSE: Blockade of the PD-1/PD-L1 axis emerged as a promising new therapeutic option for cancer that has resulted in lasting responses in metastatic renal, lung carcinomas and melanomas. Tumor PD-L1 protein expression may predict response to drugs targeting this pathway. Measurement of PD-L1 protein is limited by the lack of standardized immunohistochemistry methods and variable performance of antibodies. Our goal was to correlate PD-L1 mRNA expression with clinical variables in primary breast carcinomas.

Circulating tumor cells (CTCs) play a major role in the metastatic spread of breast cancer. CTC detection has proven to be an important parameter for predicting progression free and overall survival. Collection of CTCs is minimally invasive and can be performed more often than disseminated tumor cell (DTC) collection from bone marrow, thus providing a real-time "liquid biopsy".

Previous investigation by our laboratory found that acute hypernatremia potentiates an oxytocinergic tone that inhibits parvocellular neurosecretory neurons in the paraventricular nucleus of the hypothalamus (PVN), attenuates restraint-induced surges in corticosterone (CORT), and reduces anxiety-like behavior in male rats. To investigate the neural mechanisms mediating these effects and extend our findings to a more versatile species, we repeated our studies using laboratory mice.

Purpose

To advance our understanding how the outer eye interacts with its environment, we asked which cellular receptors are expressed in the cornea, focusing on G protein-coupled receptors.

Methods

Total RNA from the mouse cornea was subjected to next-generation sequencing using the Illumina platform. The data was analyzed with TopHat and CuffLinks software packages. Expression of a representative group of genes detected by RNA-seq was further analyzed by RT-PCR and in situ hybridization using RNAscope technology and fluorescent microscopy.

Results

Arc is an immediate early gene that is unique among neuronal mRNAs because its transcripts are transported into dendrites and accumulate near activated synapses, presumably to be translated locally. These qualities pose Arc as playing an important, yet not fully understood, role in the activity-dependent modifications of synapses that are thought to underlie memory storage. Here we show in vivo in rats that newly synthesized Arc mRNA accumulates at activated synapses and that synaptic activity simultaneously triggers mRNA decay that eliminates Arc mRNA from inactive dendritic domains.

The mammalian lung is a highly branched network in which the distal regions of the bronchial tree transform during development into a densely packed honeycomb of alveolar air sacs that mediate gas exchange.

A variety of RNA analysis technologies are available for the detection of RNA transcripts from bulk cell populations. However, the techniques for RNA detection from individual cells have been limited. Here we adapt a novel in situ signal amplification method (the RNAScope^® detection platform) for the analysis of intracellular RNAs in individual cells by flow cytometry.

BACKGROUND:
Despite the beneficial effects of type 4 dipeptidyl peptidase (DPP-4) inhibitors on glucose levels, its effects on diabetic nephropathy remain unclear.
METHOD:

Abstract