Neuro-mesenchymal interaction mediated by a β2 adrenergic-nerve growth factor feedforward loop promotes colorectal cancer progression.

Cancer-associated fibroblasts (CAFs) and nerves, components of the tumor microenvironment, have each been shown to directly promote gastrointestinal cancers. However, it remains unknown whether these cells interact with each other to regulate cancer progression. We found that in colorectal cancer (CRC) norepinephrine induces ADRB2-dependent nerve growth factor (NGF) secretion from CAFs, which in turn increases intra-tumor sympathetic innervation and norepinephrine accumulation.

An optimized protocol for isolation of murine pancreatic single cells with high yield and purity.

Here, we present a protocol for rapidly isolating single cells from the mouse pancreas, minimizing damage caused by digestive enzymes in exocrine cells. We guide you through steps to optimize the dissection sequence, enzyme composition, and operational procedures, resulting in high yields of viable pancreatic single cells. This protocol can be applied across a wide range of research areas, including single-cell sequencing, gene expression profiling, primary cell culture, and even the development of spheroids or organoids.

Future directions in preclinical and translational cancer neuroscience research.

Recent advances in cancer neuroscience necessitate the systematic analysis of neural influences in cancer as potential therapeutic targets in oncology. Here, we outline recommendations for future preclinical and translational research in this field.

PD-1 Signaling Promotes Tumor-Infiltrating Myeloid-Derived Suppressor Cells and Gastric Tumorigenesis in Mice.

Background & Aims: Immune checkpoint inhibitors have limited efficacy in many tumors. We investigated mechanisms of tumor resistance to inhibitors of programmed cell death-1 (PDCD1, also called PD-1) in mice with gastric cancer, and the role of its ligand, PD-L1.

Methods: Gastrin-deficient mice were given N-methyl-N-nitrosourea (MNU) in drinking water along with Helicobacter felis to induce gastric tumor formation; we also performed studies with H/K-ATPase-hIL1B mice, which develop spontaneous gastric tumors at the antral-corpus junction and have parietal cells that constitutively secrete interleukin 1B.

Clinically Actionable Strategies for Studying Neural Influences in Cancer.

Neuro-glial activation is a recently identified hallmark of growing cancers. Targeting tumor hyperinnervation in preclinical and small clinical trials has yielded promising antitumor effects, highlighting the need of systematic analysis of neural influences in cancer (NIC). Here, we outline the strategies translating these findings from bench to the clinic.

Interleukin-1β-induced pancreatitis promotes pancreatic ductal adenocarcinoma via B lymphocyte-mediated immune suppression.

Objective: Long-standing chronic pancreatitis is an established risk factor for pancreatic ductal adenocarcinoma (PDAC). Interleukin-1β (IL-1β) has been associated in PDAC with shorter survival. We employed murine models to investigate the mechanisms by which IL-1β and chronic pancreatitis might contribute to PDAC progression.

Adult Pancreatic Acinar Progenitor-like Populations in Regeneration and Cancer.

The bulk of the pancreas primarily comprises long-lived acinar cells that are not considered a bona fide source for stem cells. However, certain acinar subpopulations have a repopulating capacity during regeneration, raising the hypothesis as to the presence of regenerative progenitor-like populations in the adult pancreas. Here, we describe recent discoveries based on fate-mapping techniques that support the existence of progenitor-like acinar subpopulations, including active progenitor-like cells that maintain tissue homeostasis and facultative progenitor-like cells that drive tissue regeneration.

Roadmap for the Emerging Field of Cancer Neuroscience.

Mounting evidence indicates that the nervous system plays a central role in cancer pathogenesis. In turn, cancers and cancer therapies can alter nervous system form and function. This Commentary seeks to describe the burgeoning field of "cancer neuroscience" and encourage multidisciplinary collaboration for the study of cancer-nervous system interactions.

Therapeutic alternatives for supporting GPs to deprescribe opioids: a cross-sectional survey.

Background: GPs are central to opioid strategy in chronic non-cancer pain (CNCP). Lack of treatment alternatives and providers are common reasons cited for not deprescribing opioids. There are limited data about availability of multidisciplinary healthcare providers (MHCPs), such as psychologists, physiotherapists, or dietitians, who can provide broader treatments.

Cholinergic Signaling via Muscarinic Receptors Directly and Indirectly Suppresses Pancreatic Tumorigenesis and Cancer Stemness.

In many solid tumors, parasympathetic input is provided by the vagus nerve, which has been shown to modulate tumor growth. However, whether cholinergic signaling directly regulates progression of pancreatic ductal adenocarcinoma (PDAC) has not been defined. Here, we found that subdiaphragmatic vagotomy in LSL- ;-Cre (KC) mice accelerated PDAC development, whereas treatment with the systemic muscarinic agonist bethanechol restored the normal KC phenotype, thereby suppressing the accelerated tumorigenesis caused by vagotomy.

Genotyping of high-risk anal human papillomavirus (HPV): ion torrent-next generation sequencing vs. linear array.

Background: Our next generation sequencing (NGS)-based human papillomavirus (HPV) genotyping assay showed a high degree of concordance with the Roche Linear Array (LA) with as little as 1.25 ng formalin-fixed paraffin-embedded-derived genomic DNA in head and neck and cervical cancer samples. This sensitive genotyping assay uses barcoded HPV PCR broad-spectrum general primers 5+/6+ (BSGP)5+/6+ applicable to population studies, but it's diagnostic performance has not been tested in cases with multiple concurrent HPV infections.

Epithelial stem cell mutations that promote squamous cell carcinoma metastasis.

Squamous cell carcinomas (SCCs) originate in stratified epithelia, with a small subset becoming metastatic. Epithelial stem cells are targets for driver mutations that give rise to SCCs, but it is unknown whether they contribute to oncogenic multipotency and metastasis. We developed a mouse model of SCC by targeting two frequent genetic mutations in human SCCs, oncogene Kras(G12D) activation and Smad4 deletion, to mouse keratin 15-expressing (K15+) stem cells.

Reunifying families, cutting costs: housing-child welfare partnerships for permanent supportive housing.

In the absence of an adequate supply of affordable, quality housing, child welfare agencies are placed in the unenviable position of separating families to protect children from the debilitating effects of homelessness. This article presents recommendations for costeffective housing-child welfare partnerships that will shift the burden of providing adequate housing back to housing agencies. These partnerships have the potential to move child welfare agencies closer to achieving permanence and well-being for all children.