Dynamic bioinspired coculture model for probing ER breast cancer dormancy in the bone marrow niche.

Late recurrences of breast cancer are hypothesized to arise from disseminated tumor cells (DTCs) that reactivate after dormancy and occur most frequently with estrogen receptor-positive (ER) breast cancer cells (BCCs) in bone marrow (BM). Interactions between the BM niche and BCCs are thought to play a pivotal role in recurrence, and relevant model systems are needed for mechanistic insights and improved treatments. We examined dormant DTCs in vivo and observed DTCs near bone lining cells and exhibiting autophagy.

A nociceptive stress model of adolescent physical abuse induces contextual fear and cingulate nociceptive neuroplasticities.

Adolescent physical abuse impairs emotional development and evokes cingulate pathologies, but its neuronal and circuit substrates are unknown. Conditioning adolescent rabbits with noxious colorectal distension for only 2 h over 3 weeks simulated the human child abuse in amplitude, frequency, and duration. Thermal withdrawal thresholds were unchanged suggesting that sensitized spinal mechanisms may not be operable.

Purinergic Receptor Expression and Cellular Responses to Purinergic Agonists in Human Prostate Cancer Cells.

Background: Anticancer activity of extracellular nucleotides has been investigated in many types of cancer. Herein, the effects of extracellular nucleotides and the receptor profile for these nucleotides on prostate cancer (PCa) were elaborated.

Materials And Methods: PCa cell lines representing different stages of PCa were used.

Identification of Fibulin-1 as a Human Bone Marrow Stromal (HS-5) Cell-Derived Factor That Induces Human Prostate Cancer Cell Death.

Background: Previous studies showed that human bone marrow stromal HS-5 cells secreted unidentified factor(s) inducing PCa cell death. Herein, the HS-5-derived factor (HS-5 DF) was characterized and identified.

Methods: Conditioned media from confluent HS-5 cells were collected and modified for biochemical characteristic testing of HS-5 DF.

2016 Guidelines of the American Society of Mammalogists for the use of wild mammals in research and education.

Guidelines for use of wild mammal species in research are updated from Sikes et al. (2011) . These guidelines cover current professional techniques and regulations involving the use of mammals in research and teaching; they also incorporate new resources, procedural summaries, and reporting requirements.

Institutional Animal Care and Use Committee Considerations for the Use of Wildlife in Research and Education.

Ethical and effective oversight of the use of wildlife species in research and education requires consideration of issues and methods not relevant to work with traditional laboratory or domesticated animals, just as the effective oversight of biomedical research requires consideration of issues and methods not germane to wildlife research. Institutional Animal Care and Use Committees or other institutional review committees can meet their responsibilities in these disparate types of animal activities only by using resources tailored to the animals and situations encountered. Here we review the issues and the resources that facilitate effective oversight of such activities in the wildlife research arena available to researchers, institutional review committees, regulatory bodies, and accrediting bodies.

Animal Welfare Policy: Implementation in the Context of Wildlife Research--Policy Review and Discussion of Fundamental Issues.

The use of vertebrate animals in research and education in the United States is subject to a number of regulations, policies, and guidelines under the immediate oversight of Institutional Animal Care and Use Committees (IACUCs), which are charged with ensuring the ethical and appropriate use of the animal subjects. In almost all instances, this regulatory and oversight landscape of animal use has been developed around domesticated animals in biomedical research environments. When the research activities involve wild species, especially in their natural habitat rather than a laboratory, oversight personnel and investigators alike struggle with determining what constitutes ethical and appropriate activities.

Introduction to Insights Gained from Wildlife Research in the Context of Global Anthropogenic Change.

The language and subject matter offered in this issue of the ILAR Journal represent a departure from standard discourse on research animal welfare. Although the overall character of such a departure will become evident, the contributions herein reinforce and expand upon the shared, established tenets of research animal welfare. Through the work and experience of contributing wildlife research professionals, this issue of the ILAR Journal offers a diverse consortium of wildlife topics ranging from policy to conservation to disease investigation, all against the backdrop of the complexities of effective compliance and oversight when the research subjects are wild.

Dexmedetomidine and ketamine show distinct patterns of cell degeneration and apoptosis in the developing rat neonatal brain.

Objective: Early exposure to common anesthetic and sedative agents causes widespread brain cell degeneration and apoptosis in the developing rat brain, associated with persistent learning deficits in rats. This study was designed to determine whether the α2 adrenergic receptor agonist, dexmedetomidine, produces brain cell degeneration and apoptosis in postnatal day-7 rats in the same brain areas when compared to ketamine.

Methods: Systemic saline, ketamine 20 mg/kg, or dexmedetomidine at 30 or 45 μg/kg were given six times to postnatal day 7 rats (n  =  6/group) every 90 min.

Anabolic steroids alter the physiological activity of aggression circuits in the lateral anterior hypothalamus.

Syrian hamsters exposed to anabolic/androgenic steroids (AAS) during adolescence consistently show increased aggressive behavior across studies. Although the behavioral and anatomical profiles of AAS-induced alterations have been well characterized, there is a lack of data describing physiological changes that accompany these alterations. For instance, behavioral pharmacology and neuroanatomical studies show that AAS-induced changes in the vasopressin (AVP) neural system within the latero-anterior hypothalamus (LAH) interact with the serotonin (5HT) and dopamine (DA) systems to modulate aggression.

Correlation between GyrA substitutions and ofloxacin, levofloxacin, and moxifloxacin cross-resistance in Mycobacterium tuberculosis.

The newer fluoroquinolones moxifloxacin (MXF) and levofloxacin (LVX) are becoming more common components of tuberculosis (TB) treatment regimens. However, the critical concentrations for testing susceptibility of Mycobacterium tuberculosis to MXF and LVX are not yet well established. Additionally, the degree of cross-resistance between ofloxacin (OFX) and these newer fluoroquinolones has not been thoroughly investigated.

Cell-based assays using calcein acetoxymethyl ester show variation in fluorescence with treatment conditions.

The use of fluorogenic compounds in cell and molecular biology has increased in both frequency and range of applications. However, such compounds may introduce artifacts in intracellular fluorescence and cell number estimations as a consequence of interaction with exogenous stimulants, necessitating the use of adequate controls for accurate measurements and valid conclusions. Using calcein acetoxymethyl ester (AM) in combination with various exogenous cellular treatments, we report that the standard practice of direct normalization of experimental values to controls is insufficient for fluorogenic measurements.

Identification of beta-2 as a key cell adhesion molecule in PCa cell neurotropic behavior: a novel ex vivo and biophysical approach.

Prostate cancer (PCa) is believed to metastasize through the blood/lymphatics systems; however, PCa may utilize the extensive innervation of the prostate for glandular egress. The interaction of PCa and its nerve fibers is observed in 80% of PCa and is termed perineural invasion (PNI). PCa cells have been observed traveling through the endoneurium of nerves, although the underlying mechanisms have not been elucidated.

Insidious changes in stromal matrix fuel cancer progression.

Reciprocal interactions between tumor and stromal cells propel cancer progression and metastasis. A complete understanding of the complex contributions of the tumor stroma to cancer progression necessitates a careful examination of the extracellular matrix (ECM), which is largely synthesized and modulated by cancer-associated fibroblasts. This structurally supportive meshwork serves as a signaling scaffold for a myriad of biologic processes and responses favoring tumor progression.

Wildlife researchers running the permit maze.

The study of wildlife, whether in the field or in the lab, may start with a hypothesis, a literature search, or a grant proposal, but in many cases, the work will never happen unless the researcher successfully navigates a maze of permit requirements. A single project can involve multiple permits at the national and state levels, and it can take months to obtain any one permit. Therefore, permits may not have been issued at the time of protocol review, but Public Health Service Policy makes accommodations for this situation.

Fundamental differences between wildlife and biomedical research.

Non-human animals have starred in countless productions of biological research. Whether they play the lead or supporting role depends on the nature of the investigation. These differences in the roles of animals affect nearly every facet of animal involvement, including: the choice of species, the sample size, the source of individuals, and the settings in which the animals are used.

Combination of low dose of genistein and daidzein has synergistic preventive effects on isogenic human prostate cancer cells when compared with individual soy isoflavone.

The reduced incidence of prostate cancer (PCa) in Asia countries has been attributed to high soy diets, and major soy isoflavones, in particular daidzein and genistein, are thought to be the source of the beneficial and anti-cancer effects of soy foods. However, attention has been drawn to the safety of using high levels of soy isoflavones in humans, which is especially the concern for consumers taking regular soy isoflavone dietary supplements. The main objective of this study is thus to identify a soy isoflavone combination with lower levels of daidzein and genistein to be a more efficacious and safer chemo-preventive agent for PCa.

Apoptotic effects of cooked and in vitro digested soy on human prostate cancer cells.

Previous laboratory and animal studies reported that soy isoflavones were major bioactive compounds in soy to exert chemoprotection of prostate cancer. However, these studies cannot reflect the realistic effects that soy may induce through diets, and little is known about the bioavailability of isoflavones from whole soy food and their bioactivities after cooking and digestion. In this study, cooking and in vitro digestion were used to prepare soy extracts and the effects of cooking and digestion on the isoflavone contents and bioactivities of the whole soy extracts were examined.

Differential effects of vitamin D treatment on inflammatory and non-inflammatory breast cancer cell lines.

Vitamin D is a known regulator of breast cancer cell proliferation, apoptosis, migration, invasion and differentiation in vitro. Recent studies have suggested a preventative role for vitamin D in breast cancer development and suggested a possible therapeutic application of vitamin D for patients with various forms of breast cancer. Inflammatory breast cancer (IBC) is a highly aggressive and phenotypically unique form of breast cancer that has a very poor prognosis.

Increased TGF-β1-mediated suppression of growth and motility in castrate-resistant prostate cancer cells is consistent with Smad2/3 signaling.

Background: Elevated TGF-β levels are associated with prostate cancer progression. Although TGF-β is a tumor suppressor for normal epithelial and early-stage cancer cells, it may act paradoxically as a tumor promoter in more advanced cancers, although its effects are largely cell and context dependent. This study analyzed prostate cancer responses to TGF-β signaling in an isogenic model of androgen-sensitive and castration-resistant prostate cancer cells.

Overexpression of the VSSC-associated CAM, β-2, enhances LNCaP cell metastasis associated behavior.

Background: Prostate cancer (PCa) is the second-leading cause of cancer death in American men. This is due largely to the "silent" nature of the disease until it has progressed to a highly metastatic and castrate resistant state. Voltage sensitive sodium channels (VSSCs) are multimeric transmembrane protein complexes comprised of a pore-forming α subunit and one or two β subunits.