Cholesterol efflux protein, ABCA1, supports anti-cancer functions of myeloid immune cells.

Although immune therapy has seen significant advances, the majority of breast and other solid tumors do not respond or quickly develop resistance. One factor driving resistance is highly immune suppressive myeloid cells (MCs) such as macrophages. Previous work has established clinical links between cholesterol and cancer outcome, and that MC function can be regulated through disruption in cholesterol metabolism.

Advanced glycation end-products (AGEs) are lower in prostate tumor tissue and inversely related to proportion of West African ancestry.

Background: The metabolism of normal prostate relies on glycolysis, with prostate cancer having reduced glycolysis and increased aerobic metabolism. Advanced glycation end products (AGEs) accumulate in tissues as a result of age and glycolytic rate. Differential AGE levels were recently observed in prostate cancer tissues.

Loss of SELENOF Induces the Transformed Phenotype in Human Immortalized Prostate Epithelial Cells.

SELENOF is a member of the class of selenoproteins in which the amino acid selenocysteine is co-translationally inserted into the elongating peptide in response to an in-frame UGA codon located in the 3'-untranslated (3'-UTR) region of the SELENOF mRNA. Polymorphisms in the 3'-UTR are associated with an increased risk of dying from prostate cancer and these variations are functional and 10 times more frequent in the genomes of African American men. SELENOF is dramatically reduced in prostate cancer compared to benign adjacent regions.

Conventional versus drug-eluting embolic transarterial chemoembolization with doxorubicin: comparative drug delivery, pharmacokinetics, and treatment response in a rabbit VX2 tumor model.

The purpose of this study was to compare intra-tumoral drug delivery, pharmacokinetics, and treatment response after doxorubicin (DOX) conventional (c-) versus drug-eluting embolic (DEE-) transarterial chemoembolization (TACE) in a rabbit VX2 liver tumor model. Twenty-four rabbits with solitary liver tumors underwent c-TACE (n = 12) (1:2 water-in-oil emulsion, 0.6 mL volume, 2 mg DOX) or DEE-TACE (n = 12) (130,000 70-150 µm 2 mg DOX-loaded microspheres).

Soy protein supplementation in men following radical prostatectomy: a 2-year randomized, placebo-controlled clinical trial.

Background: Many studies have addressed effects of dietary supplementation with soy protein, but most have been inconsistent and few have been long-term studies in men.

Objectives: This study was a secondary analysis of body weight, blood pressure, thyroid hormones, iron status, and clinical chemistry in a 2-y trial of soy protein supplementation in middle-aged to older men.

Methods: Data were analyzed as secondary outcomes of a randomized controlled trial of dietary supplementation with 20 g/d soy protein isolate, providing 41 mg/d total isoflavones and 23 mg/d genistein, in 44- to 75-y-old men who were at risk of cancer recurrence following prostatectomy randomized to soy (n = 50) or a casein-based placebo (n  = 43).

An anti-IL-13 antibody reverses epithelial-mesenchymal transition biomarkers in eosinophilic esophagitis: Phase 2 trial results.

Background: Fibrostenosis, the most serious eosinophilic esophagitis (EoE) complication, is mediated by epithelial-mesenchymal transition (EMT). Transitioned cells contribute to pathogenesis by overproducing extracellular matrix.

Objective: Our aim was to determine whether RPC4046 (anti‒IL-13 mAb) modulates EMT biomarkers in biopsy samples from adults with active EoE in a substudy of a double-blind, placebo-controlled phase 2 trial.

A Rapid Method for Multispectral Fluorescence Imaging of Frozen Tissue Sections.

Multispectral fluorescence imaging on formalin-fixed paraffin-embedded (FFPE) tissues enables the detection of multiple markers in a single tissue sample that can provide information about antigen coexpression and spatial distribution of the markers. However, a lack of suitable antibodies for formalin-fixed tissues may restrict the nature of markers that can be detected. In addition, the staining method is time-consuming.

Unique and overlapping effects of triiodothyronine (T3) and thyroxine (T4) on sensory innervation of the chick cornea.

Multiple aspects of cornea development, including the innervation of the cornea by trigeminal axons, are sensitive to embryonic levels of thyroid hormone (TH). Although previous work showed that increased TH levels could enhance the rate of axonal extension within the cornea in a thyroxine (T4)-dependent manner, details underlying the stimulatory effect of TH on cornea innervation are unclear. Here, by examining the effects throughout all stages of cornea innervation of the two main THs, triiodothyronine (T3) and T4, we provide a more complete characterization of the stimulatory effects of TH on corneal nerves and begin to unravel the underlying molecular mechanisms.

Replicating and identifying large cell neuroblastoma using high-dose intra-tumoral chemotherapy and automated digital analysis.

Purpose: Large cell neuroblastomas (LCN) are frequently seen in recurrent, high-risk neuroblastoma but are rare in primary tumors. LCN, characterized by large nuclei with prominent nucleoli, predict a poor prognosis. We hypothesize that LCN can be created with high-dose intra-tumoral chemotherapy and identified by a digital analysis system.

Association of High miR-182 Levels with Low-Risk Prostate Cancer.

A subset of men with prostate cancer develops aggressive disease. We sought to determine whether miR-182, an miRNA with reported oncogenic functions in the prostate, is associated with biochemical recurrence and aggressive disease. Prostate epithelial miR-182 expression was quantified via in situ hybridization of two prostate tissue microarrays and by laser-capture microdissection of prostate epithelium.

GPX1 Localizes to the Nucleus in Prostate Epithelium and its Levels are not Associated with Prostate Cancer Recurrence.

Glutathione peroxidase 1 (GPX1) is an extensively studied selenium-dependent protein that reduces hydrogen and lipid peroxides to water. Because of its antioxidant function and its responsiveness to dietary intakes of selenium, an essential trace element whose levels are inversely associated with prostate cancer risk, GPX1 levels were assessed in a prostate cancer tissue microarray, comparing cases of recurrent prostate cancer following prostatectomy to non-recurrent controls. While GPX1 is generally considered as a protein that resides in both the cytoplasm and mitochondria, we detected strong nuclear staining by immunofluorescence using GPX1-specific antibodies.

Identification of a Subtype of Poorly Differentiated Invasive Ductal Carcinoma of the Breast Based on Vimentin and E-cadherin Expression.

Objective:  The use of molecular markers can identify a subgroup of tumors with distinct recurrence patterns. The present study aimed to characterize the immunohistochemical expression of vimentin (VIM), of E-cadherin (CDH1), and of cytokeratin 5 (CK5) in patients with invasive ductal carcinomas (IDCs).

Methods:  We have constructed a tissue microarray (TMA) from 87 patients with IDC of the breast.

Computer vision detects subtle histological effects of dutasteride on benign prostate.

Objective: To determine whether a computer vision-based approach applied to haematoxylin and eosin (H&E) prostate biopsy images can distinguish dutasteride-treated tissue from placebo, and identify features associated with degree of responsiveness to 5α-reductase inhibitor (5ARI) therapy.

Subjects And Methods: Our study population comprised 100 treatment-adherent men without prostate cancer assigned to dutasteride or placebo in the REDUCE trial, who had slides available from mandatory year-4 biopsies. Half of the men also provided slides from a year-2 biopsy.

Correlations of SELENOF and SELENOP genotypes with serum selenium levels and prostate cancer.

Background: Selenium status is inversely associated with the incidence of prostate cancer. However, supplementation trials have not indicated a benefit of selenium supplementation in reducing cancer risk. Polymorphisms in the gene encoding selenoprotein 15 (SELENOF) are associated with cancer incidence/mortality and present disproportionately in African Americans.

Arylsulfatase B is reduced in prostate cancer recurrences.

Background: Arylsulfatase B (ARSB) removes the 4-sulfate group from chondroitin 4-sulfate (C4S) and dermatan sulfate and is required for their degradation. Prior work showed that ARSB immunohistochemical scores were lower in malignant prostate tissue, and were associated with higher Gleason scores and recurrence.

Objective: This study aims to confirm that ARSB immunostaining of prostate tissue obtained at the time of radical prostatectomy is prognostic for prostate cancer recurrence.

BRCA1 protein expression and subcellular localization in primary breast cancer: Automated digital microscopy analysis of tissue microarrays.

Purpose: Mutations in BRCA1 are associated with familial as well as sporadic aggressive subtypes of breast cancer, but less is known about whether BRCA1 expression or subcellular localization contributes to progression in population-based settings.

Methods: We examined BRCA1 expression and subcellular localization in invasive breast cancer tissues from an ethnically diverse sample of 286 patients and 36 normal breast tissue controls. Two different methods were used to label breast cancer tissues for BRCA1: (1) Dual immunofluoresent staining with BRCA1 and cytokeratin 8/18 and (2) immunohistochemical staining using the previously validated MS110 mouse monoclonal antibody.

The miR-183 family cluster alters zinc homeostasis in benign prostate cells, organoids and prostate cancer xenografts.

The miR-183 cluster, which is comprised of paralogous miRs-183, -96 and -182, is overexpressed in many cancers, including prostate adenocarcinoma (PCa). Prior studies showed that overexpression of individual pre-miRs-182, -96 and -183 in prostate cells decreased zinc import, which is a characteristic feature of PCa tumours. Zinc is concentrated in healthy prostate 10-fold higher than any other tissue, and an >80% decrease in zinc is observed in PCa specimens.

microRNAs and DICER1 are regulated by 1,25-dihydroxyvitamin D in prostate stroma.

Vitamin D deficiency increases the risk of lethal prostate adenocarcinomas (PCa) and the majority of older men are deficient. Although PCa arises from the epithelium, the surrounding stroma has hormonal regulatory control over the epithelium and contributes to carcinogenesis. Herein, we describe regulation of microRNAs (miRs) by the active hormone dihydroxyvitamin D (1,25(OH)D) in human prostate stroma.

Epidermal growth factor prevents APOE4 and amyloid-beta-induced cognitive and cerebrovascular deficits in female mice.

Cerebrovascular (CV) dysfunction is emerging as a critical component of Alzheimer's disease (AD), including altered CV coverage. Angiogenic growth factors (AGFs) are key for controlling CV coverage, especially during disease pathology. Therefore, evaluating the effects of AGFs in vivo can provide important information on the role of CV coverage in AD.

Empirical comparison of color normalization methods for epithelial-stromal classification in H and E images.

Context: Color normalization techniques for histology have not been empirically tested for their utility for computational pathology pipelines.

Aims: We compared two contemporary techniques for achieving a common intermediate goal - epithelial-stromal classification.

Settings And Design: Expert-annotated regions of epithelium and stroma were treated as ground truth for comparing classifiers on original and color-normalized images.

Retinoid and carotenoid status in serum and liver among patients at high-risk for liver cancer.

Background: Approximately 2.7 million Americans are chronically infected with hepatitis C virus (HCV). HCV patients with cirrhosis form the largest group of persons at high risk for hepatocellular carcinoma (HCC).

A Phase II Randomized Trial of Lycopene-Rich Tomato Extract Among Men with High-Grade Prostatic Intraepithelial Neoplasia.

A diverse body of evidence suggests that lycopene might inhibit prostate cancer development. We conducted a 6-mo repeat biopsy randomized trial among men with high-grade prostatic intraepithelial neoplasia (HGPIN). Here we report results for serum lycopene, prostate specific antigen (PSA) and insulin-like growth factor (IGF) proteins, histopathological review, and tissue markers for proliferation [minichromosome maintenance protein 2 (MCM-2)] and cell cycle inhibition (p27).

Evidence that selenium binding protein 1 is a tumor suppressor in prostate cancer.

Selenium-Binding Protein 1 (SBP1, SELENBP1, hSP56) is a selenium-associated protein shown to be at lower levels in tumors, and its lower levels are frequently predictive of a poor clinical outcome. Distinguishing indolent from aggressive prostate cancer is a major challenge in disease management. Associations between SBP1 levels, tumor grade, and disease recurrence following prostatectomy were investigated by duplex immunofluorescence imaging using a tissue microarray containing tissue from 202 prostate cancer patients who experienced biochemical (PSA) recurrence after prostatectomy and 202 matched control patients whose cancer did not recur.

Dietary influences on tissue concentrations of phytanic acid and AMACR expression in the benign human prostate.

Background: Alpha-methylacyl-CoA racemase (AMACR) is an enzyme involved in fatty acid metabolism that is markedly over-expressed in virtually all prostate cancers (PCa), relative to benign tissue. One of AMACR's primary substrates, phytanic acid, is derived predominately from red meat and dairy product consumption. Epidemiological evidence suggests links between dairy/red meat intake, as well as phytanic acid levels, and elevated PCa risk.