Targeting activated PI3K/mTOR signaling overcomes acquired resistance to CDK4/6-based therapies in preclinical models of hormone receptor-positive breast cancer.

Background: Combined targeting of CDK4/6 and ER is now the standard of care for patients with advanced ER+/HER2- breast cancer. However, acquired resistance to these therapies frequently leads to disease progression. As such, it is critical to identify the mechanisms by which resistance to CDK4/6-based therapies is acquired and also identify therapeutic strategies to overcome resistance.

Obese ZDF rats fermented resistant starch with effects on gut microbiota but no reduction in abdominal fat.

Scope: To determine if whole-grain (WG) flour with resistant starch (RS) will produce greater fermentation than isolated RS in obese Zucker Diabetic Fatty (ZDF) rats, and whether greater fermentation results in different microbiota, reduced abdominal fat, and increased insulin sensitivity.

Methods And Results: This study utilized four groups fed diets made with either isolated digestible control starch, WG control flour (6.9% RS), isolated RS-rich corn starch (25% RS), or WG corn flour (25% RS).

Utility of whole-genome sequencing for detection of newborn screening disorders in a population cohort of 1,696 neonates.

Purpose: To assess the potential of whole-genome sequencing (WGS) to replicate and augment results from conventional blood-based newborn screening (NBS).

Methods: Research-generated WGS data from an ancestrally diverse cohort of 1,696 infants and both parents of each infant were analyzed for variants in 163 genes involved in disorders included or under discussion for inclusion in US NBS programs. WGS results were compared with results from state NBS and related follow-up testing.

Videotaped behavior as a predictor of clinical outcome in rhesus macaques (Macaca mulatta).

Understanding the behavior of laboratory NHP facilitates health assessment and clinical care. We sought to characterize the behavior of critically ill rhesus macaques (Macaca mulatta) and determine whether specific behaviors or behavioral changes might facilitate the determination of prognosis and clinical endpoints. Twenty-two critically-ill subjects were videorecorded after they were removed from the outdoor breeding colony for diagnostic work-up and treatment.

Household transmission of 2009 pandemic influenza A (H1N1) and nonpharmaceutical interventions among households of high school students in San Antonio, Texas.

San Antonio, Texas, was one of the first metropolitan areas where 2009 pandemic influenza A (H1N1) virus (pH1N1) was detected. Identification of laboratory-confirmed pH1N1 in 2 students led to a preemptive 8-day closure of their high school. We assessed transmission of pH1N1 and changes in adoption of nonpharmaceutical interventions (NPIs) within households of students attending the affected school.

A Smac mimetic rescue screen reveals roles for inhibitor of apoptosis proteins in tumor necrosis factor-alpha signaling.

Smac mimetic compounds targeting the inhibitor of apoptosis proteins (IAP) baculoviral IAP repeat-3 domain are presumed to reduce the threshold for apoptotic cell death by alleviating caspase-9 repression. We explored this tenet in an unbiased manner by searching for small interfering RNAs that are able to confer resistance to the Smac mimetic compound LBW242. Among the screening hits were multiple components of the tumor necrosis factor alpha (TNFalpha) signaling pathway as well as X-linked inhibitor of apoptosis (XIAP) itself.

RNA interference technologies and their use in cancer research.

Purpose Of Review: Recently, RNA interference has evolved into a powerful research tool to functionally characterize genes. Genome-wide RNA interference reagents can study the loss-of-function phenotypes of candidate genes in the context of various disease model systems. In this review, we discuss the data from the most recent studies using RNA interference reagents with a focus on RNA interference-based genomic screening as a tool to expand our knowledge about the molecular basis of cancer.

Production of gastrin-releasing peptide by a non-small cell lung carcinoma cell line adapted to serum-free and growth factor-free conditions.

Gastrin-releasing peptide is an important growth-modulating factor in developing lung epithelium. It is known to be produced by small cell carcinomas of the lung, and an autocrine loop involving gastrin-releasing peptide and its receptor has been demonstrated in many small cell lung tumors. We investigated whether such an autocrine loop could also be demonstrated in non-small cell lung carcinoma, since gastrin-releasing peptide is known to stimulate human bronchial epithelial cells, from which non-small cell tumors should emerge.

Effects of bombesin and gastrin-releasing peptide on human bronchial epithelial cells from a series of donors: individual variation and modulation by bombesin analogs.

Human pulmonary neuroendocrine cells produce a variety of hormones, including mammalian bombesin (BN) or gastrin-releasing peptide (GRP). Neuroendocrine cell hyperplasia and increased release of BN-like peptides occur in several diseases of the airways, including chronic obstructive pulmonary disease (COPD) and bronchopulmonary dysplasia. Growth stimulation of human bronchial epithelial cells by BN, as measured in a colony-forming assay, has been reported previously (Willey et al.

Neurogenic pulmonary edema in a pulmonary normotensive model.

In the present study our aim was to determine whether or not neurogenic pulmonary edema would develop from a brief pulse of intracranial pressure (ICP) in the absence of any obvious pulmonary hypertension. There were three groups of cats: sham-operated controls, ICP only, and ICP plus variable occlusion of the pulmonary artery. Partial occlusion of the pulmonary artery was carried out by placing a ligature around the pulmonary trunk and mechanically constricting the artery to maintain pulmonary arterial pressure (PAP) and left atrial pressure (LAP) at pre-ICP levels.