Interrogating Estrogen Signaling Pathways in Human ER-Positive Breast Cancer Cells Forming Bone Metastases in Mice.

Breast cancer bone metastases (BMET) are incurable, primarily osteolytic, and occur most commonly in estrogen receptor-α positive (ER+) breast cancer. ER+ human breast cancer BMET modeling in mice has demonstrated an estrogen (E2)-dependent increase in tumor-associated osteolysis and bone-resorbing osteoclasts, independent of estrogenic effects on tumor proliferation or bone turnover, suggesting a possible mechanistic link between tumoral ERα-driven osteolysis and ER+ bone progression. To explore this question, inducible secretion of the osteolytic factor, parathyroid hormone-related protein (PTHrP), was utilized as an in vitro screening bioassay to query the osteolytic potential of estrogen receptor- and signaling pathway-specific ligands in BMET-forming ER+ human breast cancer cells expressing ERα, ERß, and G protein-coupled ER.

Intrapatient comparison of atopic dermatitis skin transcriptome shows differences between tape-strips and biopsies.

Background: Our knowledge of etiopathogenesis of atopic dermatitis (AD) is largely derived from skin biopsies, which are associated with pain, scarring and infection. In contrast, tape-stripping is a minimally invasive, nonscarring technique to collect skin samples.

Methods: To construct a global AD skin transcriptomic profile comparing tape-strips to whole-skin biopsies, we performed RNA-seq on tape-strips and biopsies taken from the lesional skin of 20 moderate-to-severe AD patients and the skin of 20 controls.

Crisaborole reverses dysregulation of the mild to moderate atopic dermatitis proteome toward nonlesional and normal skin.

Background: Safe and effective long-term topical treatments for atopic dermatitis (AD) remain limited.

Objective: In this phase 2a, single-center, intrapatient, and vehicle-controlled study, we examine the mechanism of action of crisaborole 2% ointment, a topical nonsteroidal PDE4 (phosphodiesterase-4) inhibitor, in a proteomic analysis of 40 adults with mild to moderate AD and 20 healthy subjects.

Methods: Within the AD cohort, 2 target lesions were randomized in an intrapatient (1:1) manner to double-blind crisaborole/vehicle applied twice daily for 14 days.

Delayed type hypersensitivity reactions to various allergens may differently model inflammatory skin diseases.

Background: Treatment of inflammatory skin diseases, including atopic dermatitis (AD) and psoriasis, is undergoing transformative changes, highlighting the need to develop experimental models of skin inflammation in humans to predict treatment responses.

Methods: We topically or intradermally administered four common sensitizers (dust mite (DM), diphencyprone (DPCP), nickel (Ni), and purified protein derivative (PPD)) to the backs of 40 healthy patients and the skin hypersensitivity response was biopsied and evaluated using immunohistochemistry, RNA-seq, and RT-PCR.

Results: All agents induced strong increases in cellular infiltrates (T-cells and dendritic cells) as compared to untreated skin (p < .

Current emerging and investigational drugs for the treatment of chronic hand eczema.

Introduction: Chronic hand eczema (CHE) is a highly prevalent, burdensome condition associated with functional impairment. Currently, topical therapeutics are the mainstay of CHE management. However, many cases are refractory to existing topical therapeutics, and the few existing systemic options are often limited in efficacy and by their side effect profiles.

Accuracy of Magnetic Resonance Imaging for Identifying Ovarian Cancer in a Community-Based Setting.

Many ovarian or adnexal masses have an indeterminate appearance on ultrasound that can raise concerns about cancer. Although magnetic resonance imaging (MRI) has been reported to reliably distinguish between benign and malignant masses, studies evaluating the accuracy of MRI in community-based practice settings are lacking. Women who underwent MRI to further evaluate an ultrasound-detected adnexal mass in 2016-2017 within a large community-based health system were identified.

Osteolytic effects of tumoral estrogen signaling in an estrogen receptor-positive breast cancer bone metastasis model.

Aim: Estrogen receptor α-positive (ER+) subtypes of breast cancer have the greatest predilection for forming osteolytic bone metastases (BMETs). Because tumor-derived factors mediate osteolysis, a possible role for tumoral ERα signaling in driving ER+ BMET osteolysis was queried using an estrogen (E)-dependent ER+ breast cancer BMET model.

Methods: Female athymic Foxn1 mice were inoculated with human ER+ MCF-7 breast cancer cells via the left cardiac ventricle post-E pellet placement, and age- and dose-dependent E effects on osteolytic ER+ BMET progression, as well as direct bone effects of E, were determined.

Early adversity and depressive symptoms among early adolescent girls: the mediating role of exposure to recent interpersonal acute stress.

Early adversity confers risk for depression in part through its association with (i.e., proximal) acute stress.

Curcumin Inhibition of TGFβ signaling in bone metastatic breast cancer cells and the possible role of oxidative metabolites.

TGFβ signaling promotes progression of bone-metastatic (BMET) breast cancer (BCa) cells by driving tumor-associated osteolysis, a hallmark of BCa BMETs, thus allowing for tumor expansion within bone. Turmeric-derived bioactive curcumin, enriched in bone via local enzymatic deconjugation of inactive circulating curcumin-glucuronides, inhibits osteolysis and BMET progression in human xenograft BCa BMET models by blocking tumoral TGFβ signaling pathways mediating osteolysis. This is a unique antiosteolytic mechanism in contrast to current osteoclast-targeting therapeutics.

A Role for TGFβ Signaling in Preclinical Osteolytic Estrogen Receptor-Positive Breast Cancer Bone Metastases Progression.

While tumoral Smad-mediated transforming growth factor β (TGFβ) signaling drives osteolytic estrogen receptor α-negative (ER-) breast cancer bone metastases (BMETs) in preclinical models, its role in ER+ BMETs, representing the majority of clinical BMETs, has not been documented. Experiments were undertaken to examine Smad-mediated TGFβ signaling in human ER+ cells and bone-tropic behavior following intracardiac inoculation of estrogen (E)-supplemented female nude mice. While all ER+ tumor cells tested (ZR-75-1, T47D, and MCF-7-derived) expressed TGFβ receptors II and I, only cells with TGFβ-inducible Smad signaling (MCF-7) formed osteolytic BMETs in vivo.

Epidemiology and Characterization of Atopic Dermatitis in East Asian Populations: A Systematic Review.

Introduction: As atopic dermatitis (AD) grows increasingly prevalent in Asian populations worldwide, understanding how environmental, genetic, and cultural factors uniquely influence AD in Asians is essential for informing disease management. Our objectives were to characterize the epidemiology of AD in East Asian populations with sensitivity to the changing demographics of AD in these populations and the effects of urbanization and immigration.

Methods: A systematic review was performed on epidemiologic studies of AD in East Asian populations over the past 10 years.

Skeletal impact of 17β-estradiol in T cell-deficient mice: age-dependent bone effects and osteosarcoma formation.

Estrogen (E)-dependent ER+ breast cancer, the most common breast cancer subtype, is also the most likely to metastasize to bone and form osteolytic lesions. However, ER+ breast cancer bone metastasis human xenograft models in nude mice are rarely studied due to complexities associated with distinguishing possible tumoral vs. bone microenvironmental effects of E.

Pre-diagnostic dynamic HPV16 IgG seropositivity and risk of oropharyngeal cancer.

Objective: The aim of this study was to determine the association of HPV16 antibodies (Abs) and oropharyngeal cancer (OPC) risk in sera obtained prior to clinical diagnosis.

Methods: We identified 92 participants with incident OPC and 460 matched controls from the Janus Serum Bank Cohort in Norway. Archived tumor specimens were requested for a subset of the cases.

Biologic predictors of serologic responses to HPV in oropharyngeal cancer: The HOTSPOT study.

Objectives: We hypothesized that viral and host factors impact the serologic responses to HPV early antigens in HPV-positive oropharyngeal cancer (HPVOPC).

Materials And Methods: We conducted a multicenter study to measure HPV16-specific IgG among patients with HPVOPC, their long-term sexual partners, and healthy volunteers. Risk factor surveys and rinse and gargle specimens were collected.

HPV Serum Antibodies as Predictors of Survival and Disease Progression in Patients with HPV-Positive Squamous Cell Carcinoma of the Oropharynx.

Purpose: Oropharyngeal carcinoma positive for human papillomavirus type 16 (HPV16) has a significantly better prognosis than oropharyngeal carcinoma unrelated to HPV. Within HPV16-positive oropharyngeal carcinoma, biomarkers of prognosis are urgently needed to individualize care. We hypothesized that serum antibodies specific to HPV16, the major HPV type causing oropharyngeal carcinoma, have biologic relevance and are potential biomarkers for improved prognosis among patients with HPV16-positive oropharyngeal carcinoma.

HPV16 antibodies as risk factors for oropharyngeal cancer and their association with tumor HPV and smoking status.

Background: Antibodies (Abs) to the HPV16 proteome increase risk for HPV-associated OPC (HPVOPC). The goal of this study was to investigate the association of a panel of HPV16 Abs with risk for OPC as well as the association of these Abs with tumor HPV and smoking status among patients with OPC.

Methods: IgG Abs to the HPV16 antigens E1, E2, E4, E5, E6, E7, L1, L2 were quantified using a programmable ELISA assay.

Clinically significant effects of group cognitive behavioral therapy on spouse caregivers' mental health and cognitive functioning: a pilot study.

The objective of this pilot study was to investigate whether group cognitive behavioral therapy (CBT) resulted in clinically meaningful improvements in caregiver mood, burden, and cognition. We screened 97 caregivers in Toronto, Canada, of whom 25 with DSM-IV disorders began the 13-week CBT intervention, and 12 completed therapy and the 3-month follow-up. Each caregiver experienced clinically significant improvement on at least 2 of the following outcomes: diagnostic criteria, mood, attention, memory, and caregiver burden.

Feasibility of recruiting spouses with DSM-IV diagnoses for caregiver interventions.

Background: Reviews and meta-analyses suggest that caregiver interventions have only been modestly effective in reducing caregiver distress. One possible reason is that many intervention studies have recruited heterogeneous caregivers with subclinical symptoms. This study examined the feasibility of recruiting a more homogenous group of caregivers with high clinical distress levels for an intensive therapy intervention.

Oxidative stress disrupts internalization and endocytic trafficking of transferrin in a human malignant keratinocyte line.

Oxidative stress is involved in epidermal cell pathology. One potential mechanism for this toxicity that has previously not been explored in epidermal cells involves modulation of endocytic trafficking and the implications that such modulation can have for altered cell function. The effects of oxidative stress on endocytic trafficking are not well understood, particularly relating to how general or cell-type specific such effects may be.