Osteocalcin protects islet identity in low-density lipoprotein receptor knockout mice on high-fat diet.

Metabolic syndrome (MetS) is an increasing global health threat and strong risk factor for type 2 diabetes (T2D). MetS causes both hyperinsulinemia and islet size overexpansion, and pancreatic β-cell failure impacts insulin and proinsulin secretion, mitochondrial density, and cellular identity loss. The low-density lipoprotein receptor knockout (LDLr-/-) model combined with high-fat diet (HFD) has been used to study alterations in multiple organs, but little is known about the changes to β-cell identity resulting from MetS.

Current State of Diffusion-Weighted Imaging and Diffusion Tensor Imaging for Traumatic Brain Injury Prognostication.

Advanced imaging techniques are needed to assist in providing a prognosis for patients with traumatic brain injury (TBI), particularly mild TBI (mTBI). Diffusion tensor imaging (DTI) is one promising advanced imaging technique, but has shown variable results in patients with TBI and is not without limitations, especially when considering individual patients. Efforts to resolve these limitations are being explored and include developing advanced diffusion techniques, creating a normative database, improving study design, and testing machine learning algorithms.

Desmoplakin (Dsp) conditional knockout in NR5A1+ somatic cells affects germ cell survival in developing mouse gonads.

Cell to cell interactions are crucial for morphogenesis and tissue formation. Desmoplakin (encoded by the Dsp gene) is a component of desmosomes and anchors the transmembrane adhesion proteins to the cytoskeleton. Its role in gonad development remains vague.

Catheter-based Techniques for Terminal Cancer Pain: A Review of Nonneuraxial Interventions with Clinical Implications for End-of-Life Pain Management.

Background: Evidence suggests that a significant proportion of terminal cancer patients have uncontrolled or inadequately controlled pain when using the World Health Organization (WHO) analgesic ladder approach. The use of interventional techniques has proven to reduce pain that is refractory to conventional methods. However, despite the use of well-established techniques (e.

Inhibition of GATA2 in prostate cancer by a clinically available small molecule.

Castration-resistant prostate cancer (CRPC) remains highly lethal and in need of novel, actionable therapeutic targets. The pioneer factor GATA2 is a significant prostate cancer (PC) driver and is linked to poor prognosis. GATA2 directly promotes androgen receptor (AR) gene expression (both full-length and splice-variant) and facilitates AR binding to chromatin, recruitment of coregulators, and target gene transcription.

Immune checkpoint inhibitor related hypophysitis: diagnostic criteria and recovery patterns.

Data on the diagnosis, natural course and management of immune checkpoint inhibitor (ICI)-related hypophysitis (irH) are limited. We propose this study to validate the diagnostic criteria, describe characteristics and hormonal recovery and investigate factors associated with the occurrence and recovery of irH. A retrospective study including patients with suspected irH at the University of Texas MD Anderson Cancer Center from 5/2003 to 8/2017 was conducted.

Phase 2 Study of Anti-Human Cytomegalovirus Monoclonal Antibodies for Prophylaxis in Hematopoietic Cell Transplantation.

Human cytomegalovirus (HCMV) can cause significant disease in immunocompromised patients, and treatment options are limited by toxicities. CSJ148 is a combination of two anti-HCMV human monoclonal antibodies (LJP538 and LJP539) that bind to and inhibit the functions of viral HCMV glycoprotein B (gB) and the pentameric complex, consisting of glycoproteins gH, gL, UL128, UL130, and UL131. In this phase 2, randomized, placebo-controlled trial, we evaluated the safety and efficacy of CSJ148 for prophylaxis of HCMV in patients undergoing allogeneic hematopoietic stem cell transplantation.

Hepatocellular carcinoma response to transcatheter arterial chemoembolisation using automatically generated pre-therapeutic tumour volumes by a random forest-based segmentation protocol.

Aim: To demonstrate the feasibility of correlating pre-therapeutic volumes and residual liver volume (RLV) with clinical outcomes: time to progression (TTP) and overall survival (OS) in hepatocellular carcinoma (HCC) treated with transcatheter arterial chemoembolisation (TACE).

Materials And Methods: TTP was calculated from a database of 105 patients, receiving first-line treatment with TACE. TTP cut-off for stratifying patients into responders and non-responders was 28 weeks.

Integrative proteomic and transcriptomic analysis provides evidence for TrkB (NTRK2) as a therapeutic target in combination with tyrosine kinase inhibitors for non-small cell lung cancer.

While several molecular targets have been identified for adenocarcinoma (ACA) of the lung, similar drivers with squamous cell carcinoma (SCC) are sparse. We compared signaling pathways and potential therapeutic targets in lung SCC and ACA tumors using reverse phase proteomic arrays (RPPA) from two independent cohorts of resected early stage NSCLC patients: a testing set using an MDACC cohort (N=140) and a validation set using the Cancer Genome Atlas (TCGA) cohorts. We identified multiple potentially targetable proteins upregulated in SCC, including NRF2, Keap1, PARP, TrkB, and Chk2.

Development of the National Cancer Institute's patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE).

The standard approach for documenting symptomatic adverse events (AEs) in cancer clinical trials involves investigator reporting using the National Cancer Institute's (NCI's) Common Terminology Criteria for Adverse Events (CTCAE). Because this approach underdetects symptomatic AEs, the NCI issued two contracts to create a patient-reported outcome (PRO) measurement system as a companion to the CTCAE, called the PRO-CTCAE. This Commentary describes development of the PRO-CTCAE by a group of multidisciplinary investigators and patient representatives and provides an overview of qualitative and quantitative studies of its measurement properties.

Randomized, controlled pilot trial of bupropion for pregnant smokers: challenges and future directions.

Objective: The aim of the study is to conduct an initial pilot trial evaluating the feasibility, safety, and efficacy of bupropion for smoking cessation in pregnancy.

Study Design: A randomized, double-blind, parallel-group pilot study of bupropion versus placebo with 50 pregnant smokers was planned. Eligibility criteria were restrictive (e.

Weekly liposomal amphotericin B as secondary prophylaxis for invasive fungal infections in patients with hematological malignancies.

There have been no published studies evaluating the efficacy and safety of weekly liposomal amphotericin B as secondary prophylaxis in leukemic patients with invasive fungal infections (IFIs). We found in a retrospective review of our experience with 14 such patients admitted from 2003-2009 that the use of this approach was associated with frequent relapse of IFIs (36%) and kidney injury (36%).

RAGE and RAGE ligands in cancer.

The receptor for advanced glycation end-products (RAGE) is a multifunctional receptor with multiple ligands that is known to play a key role in several diseases, including diabetes, arthritis, and Alzheimer's disease. Recent evidence indicates that this receptor also has an important role in cancer. RAGE ligands, which include the S100/calgranulins and high-mobility group box 1 (HMGB1) ligands, are expressed and secreted by cancer cells and are associated with increased metastasis and poorer outcomes in a wide variety of tumors.

Presence of malignant tumor cells in persistent neck disease after radiotherapy for advanced squamous cell carcinoma of the oropharynx is associated with poor survival.

Non-surgical therapy consisting of external beam radiation with or without chemotherapy is an effective treatment for patients with squamous cell carcinoma (SCC) of the oropharynx with advanced neck disease (N2a or greater). However, many of these patients have to undergo a neck dissection for clinically persistent regional disease. It is reported that nearly 50% of the neck dissection specimens contain residual viable tumor cells that may indicate partial radiation failure and as a consequence poor survival.

Genetic markers useful for distinguishing between organ-confined and locally advanced prostate cancer.

Prostate cancer is one of the most commonly diagnosed cancers and the second leading cause of cancer deaths among men in the United States. In this study, we performed comparative genomic hybridization (CGH) on 45 primary prostate adenocarcinomas to determine genetic markers that could be useful for distinguishing between organ-confined and locally advanced prostate cancer. Of these tumors, 24 were pT2 stage, 21 were pT3b; 20 had low Gleason scores (GS), 25 had high GS.

Interleukin 10 suppresses tumor growth and metastasis of human melanoma cells: potential inhibition of angiogenesis.

Interleukin 10 (IL-10) inhibits the production of a wide range of cytokines in various cell types. The purpose of this study was to determine whether the expression of the IL-10 gene can influence tumor growth and metastatic properties of human melanoma cells. The human melanoma cell line, A375P, which does not produce endogenous IL-10, was transfected with a hygromycin expression vector (control) or a vector containing full-length murine IL-10 cDNA.

Familial versus sporadic breast cancer.

Background: Studies comparing patients with familial and sporadic breast cancer have indicated that a family history of the disease can increase a woman's risk for having the disease twofold to threefold and that patients with familial breast cancer have a younger age at diagnosis and have a higher frequency of bilateral disease than those with sporadic breast cancer. Also, at least four types of breast cancers have been shown to be inherited. These findings led to the hypothesis that familial and sporadic breast cancer are the consequence of two biologically distinct mechanisms.