Prognostic impact of HOTAIR expression is restricted to ER-negative breast cancers.

Expression of HOX transcript antisense intergenic RNA (HOTAIR), a large intergenic noncoding RNA (lincRNA), has been described as a metastases-associated lincRNA in various cancers including breast, liver and colon cancer cancers. We sought to determine if expression of HOTAIR could be used as a surrogate for assessing nodal metastases and evaluated RNA in situ hybridization (RNA-ISH) assay in a tissue microarray constructed from 133 breast cancer patients. The prognostic value of HOTAIR was further validated in large cohorts using The Cancer Genome Atlas (TCGA) breast cancer subjects.

Predisposing factors for dural tear in patients undergoing lumbar spine surgery.

OBJECT The purpose of this prospective cohort study was to identify risk factors for incidental durotomies in lumbar spine surgery. The authors hypothesized that the incidence of durotomy would be higher in cases involving multiple operations. METHODS The authors prospectively evaluated 523 patients who underwent lumbar and thoracolumbar spine surgery.

An international study to increase concordance in Ki67 scoring.

Although an important biomarker in breast cancer, Ki67 lacks scoring standardization, which has limited its clinical use. Our previous study found variability when laboratories used their own scoring methods on centrally stained tissue microarray slides. In this current study, 16 laboratories from eight countries calibrated to a specific Ki67 scoring method and then scored 50 centrally MIB-1 stained tissue microarray cases.

NF-κB-dependent and -independent epigenetic modulation using the novel anti-cancer agent DMAPT.

The transcription factor nuclear factor-kappaB (NF-κB) is constitutively active in several cancers and is a target of therapeutic development. We recently developed dimethylaminoparthenolide (DMAPT), a clinical grade water-soluble analog of parthenolide, as a potent inhibitor of NF-κB and demonstrated in vitro and in vivo anti-tumor activities in multiple cancers. In this study, we show DMAPT is an epigenetic modulator functioning in an NF-κB-dependent and -independent manner.

Predicting early brain metastases based on clinicopathological factors and gene expression analysis in advanced HER2-positive breast cancer patients.

The overexpression or amplification of the human epidermal growth factor receptor 2 gene (HER2/neu) is associated with high risk of brain metastasis (BM). The identification of patients at highest immediate risk of BM could optimize screening and facilitate interventional trials. We performed gene expression analysis using complementary deoxyribonucleic acid-mediated annealing, selection, extension and ligation and real-time quantitative reverse transcription PCR (qRT-PCR) in primary tumor samples from two independent cohorts of advanced HER2 positive breast cancer patients.

The association between body mass index and mortality in incident dialysis patients.

Objectives: To study the body mass index (BMI) trajectory in patients with incident end-stage kidney disease and its association with all-cause mortality.

Methods: This longitudinal cohort study included 17022 adult patients commencing hemodialysis [HD] (n = 10860) or peritoneal dialysis [PD] (n = 6162) between 2001 and 2008 and had ≥6-month follow-up and ≥2 weight measurements, using the Australia and New Zealand Dialysis and Transplant Registry data. The association of time-varying BMI with all-cause mortality was explored using multivariate Cox regression models.

Phase I Study of Amrubicin and Cyclophosphamide in Patients With Advanced Solid Organ Malignancies: HOG LUN 07-130.

Objectives: Relapsed small cell lung cancer (SCLC) has limited treatment options. Anthracyclines and cyclophosphamide have shown synergy in many tumors. Amrubicin (AMR) and cyclophosphamide both have single-agent activity in SCLC.

Toward a better understanding of direct vertebral rotation for AIS surgery: development of a multisegmental biomechanical model and factors affecting correction.

Background Context: The direct vertebral rotation (DVR) technique involves vertebral manipulation by the application of force in the transverse plane using a pedicle screw as the anchor point. The biomechanics of this technique has not been well studied, and the applied derotation force may affect cosmetic outcome and potential complications.

Purpose: The purpose of the study was to develop an in vitro biomechanical model replicating DVR and examine the effects of screw placement, derotation direction, and segmental versus en bloc rotation on correction.

Expression levels of SF3B3 correlate with prognosis and endocrine resistance in estrogen receptor-positive breast cancer.

De novo or acquired resistance to endocrine therapy limits its utility in a significant number of estrogen receptor-positive (ER-positive) breast cancers. It is crucial to identify novel targets for therapeutic intervention and improve the success of endocrine therapies. Splicing factor 3b, subunit 1 (SF3B1) mutations are described in luminal breast cancer albeit in low frequency.

The rationale and design of the Beta-blocker to LOwer CArdiovascular Dialysis Events (BLOCADE) Feasibility Study.

Aims: The Beta-blocker to LOwer CArdiovascular Dialysis Events (BLOCADE) Feasibility Study aims to determine the feasibility of a large-scale randomized controlled trial with clinical endpoints comparing the beta-blocking agent carvedilol with placebo in patients receiving dialysis.

Methods: The BLOCADE Feasibility Study is a randomized, double-blind, placebo-controlled, parallel group feasibility study comparing the beta-blocking agent carvedilol with placebo. Patients receiving dialysis for ≥3 months and who are aged ≥50 years, or who are ≥18 years and have diabetes or cardiovascular disease, were eligible.

Towards large-scale histopathological image analysis: hashing-based image retrieval.

Automatic analysis of histopathological images has been widely utilized leveraging computational image-processing methods and modern machine learning techniques. Both computer-aided diagnosis (CAD) and content-based image-retrieval (CBIR) systems have been successfully developed for diagnosis, disease detection, and decision support in this area. Recently, with the ever-increasing amount of annotated medical data, large-scale and data-driven methods have emerged to offer a promise of bridging the semantic gap between images and diagnostic information.

The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014.

Background: The morphological evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer (BC) is gaining momentum as evidence strengthens for the clinical relevance of this immunological biomarker. Accumulating evidence suggests that the extent of lymphocytic infiltration in tumor tissue can be assessed as a major parameter by evaluation of hematoxylin and eosin (H&E)-stained tumor sections. TILs have been shown to provide prognostic and potentially predictive value, particularly in triple-negative and human epidermal growth factor receptor 2-overexpressing BC.

Role of lncRNAs in health and disease-size and shape matter.

Most of the mammalian genome including a large fraction of the non-protein coding transcripts has been shown to be transcribed. Studies related to these non-coding RNA molecules have predominantly focused on smaller molecules like microRNAs. In contrast, long non-coding RNAs (lncRNAs) have long been considered to be transcriptional noise.

Gene Expression Analysis Reveals Distinct Pathways of Resistance to Bevacizumab in Xenograft Models of Human ER-Positive Breast Cancer.

Bevacizumab, the recombinant antibody targeting vascular endothelial growth factor (VEGF), improves progression-free but not overall survival in metastatic breast cancer. To seek further insights in resistance mechanisms to bevacizumab at the molecular level, we developed VEGF and non-VEGF-driven ER-positive MCF7-derived xenograft models allowing comparison of tumor response at different timepoints. VEGF gene (MV165) overexpressing xenografts were initially sensitive to bevacizumab, but eventually acquired resistance.

A randomized, placebo-controlled trial of pentoxifylline on erythropoiesis-stimulating agent hyporesponsiveness in anemic patients with CKD: the Handling Erythropoietin Resistance With Oxpentifylline (HERO) trial.

Background: Erythropoiesis-stimulating agent (ESA)-hyporesponsive anemia is common in chronic kidney disease (CKD). Pentoxifylline shows promise as a treatment for ESA-hyporesponsive anemia, but has not been rigorously evaluated.

Study Design: Multicenter, double-blind, randomized, controlled trial.

Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199.

Purpose: Recent studies suggest that tumor-infiltrating lymphocytes (TILs) are associated with disease-free (DFS) and overall survival (OS) in operable triple-negative breast cancer (TNBC). We seek to validate the prognostic impact of TILs in primary TNBCs in two adjuvant phase III trials conducted by the Eastern Cooperative Oncology Group (ECOG).

Patients And Methods: Full-face hematoxylin and eosin–stained sections of 506 tumors from ECOG trials E2197 and E1199 were evaluated for density of TILs in intraepithelial (iTILs) and stromal compartments (sTILs).

End-stage kidney disease due to Alport syndrome: outcomes in 296 consecutive Australia and New Zealand Dialysis and Transplant Registry cases.

Background: Alport syndrome is a rare inheritable renal disease. Clinical outcomes for patients progressing to end-stage kidney disease (ESKD) are not well described.

Methods: This study aimed to investigate the characteristics and clinical outcomes of patients from Australia and New Zealand commencing renal replacement therapy (RRT) for ESKD due to Alport syndrome between 1965 and 1995 (early cohort) and between 1996 and 2010 (contemporary cohort) compared with propensity score-matched, RRT-treated, non-Alport ESKD controls.

A nephrology guide to reading and using systematic reviews of randomized trials.

Conscientious integration of the best available evidence in the care of an individual patient could be challenging for a busy clinician. A well-conducted systematic review can adequately inform not only the clinicians, but also the policy makers and researchers about the benefits and risks of a particular intervention. In this article, we describe how to critically appraise the methods and interpret the results of a systematic review of interventional trials and apply the findings of a systematic review to the clinical questions.

DNA double-strand break repair genes and oxidative damage in brain metastasis of breast cancer.

Background: Breast cancer frequently metastasizes to the brain, colonizing a neuro-inflammatory microenvironment. The molecular pathways facilitating this colonization remain poorly understood.

Methods: Expression profiling of 23 matched sets of human resected brain metastases and primary breast tumors by two-sided paired t test was performed to identify brain metastasis-specific genes.

Phenotypic plasticity in normal breast derived epithelial cells.

Background: Normal, healthy human breast tissue from a variety of volunteer donors has become available for research thanks to the establishment of the Susan G. Komen for the Cure® Tissue Bank at the IU Simon Cancer Center (KTB). Multiple epithelial (K-HME) and stromal cells (K-HMS) were established from the donated tissue.

NUT midline carcinomas in the thymic region.

NUT midline carcinomas (NMCs) are rare tumors described predominantly in the pediatric age group. We recently reported two cases of these tumors occurring in the thymic region. In order to establish the true incidence of these tumors, we examined a large series of thymic carcinomas for morphological features of NUT tumor and further assessed the expression of NUTM1 (also known as NUT) protein by immunohistochemistry.

ITMIG consensus statement on the use of the WHO histological classification of thymoma and thymic carcinoma: refined definitions, histological criteria, and reporting.

Introduction: The 2004 version of the World Health Organization classification subdivides thymic epithelial tumors into A, AB, B1, B2, and B3 (and rare other) thymomas and thymic carcinomas (TC). Due to a morphological continuum between some thymoma subtypes and some morphological overlap between thymomas and TC, a variable proportion of cases may pose problems in classification, contributing to the poor interobserver reproducibility in some studies.

Methods: To overcome this problem, hematoxylin-eosin-stained and immunohistochemically processed sections of prototypic, "borderland," and "combined" thymomas and TC (n = 72) were studied by 18 pathologists at an international consensus slide workshop supported by the International Thymic Malignancy Interest Group.