A multicenter randomized trial of the effects of exercise dose and type on psychosocial distress in breast cancer patients undergoing chemotherapy.

Background: Exercise may improve psychosocial distress in patients with cancer; however, few studies have examined the effects of different types or doses of exercise, or whether exercise effects are related to baseline depression levels.

Methods: In a multicenter trial in Canada, we randomized 301 patients with breast cancer initiating chemotherapy to thrice weekly, supervised exercise consisting of either a standard dose of 25 to 30 minutes of aerobic exercise (STAN; n = 96), a higher dose of 50 to 60 minutes of aerobic exercise (HIGH; n = 101), or a combined dose of 50 to 60 minutes of aerobic and resistance exercise (COMB; n = 104). The primary endpoint was depression assessed by the Center for Epidemiological Studies-Depression scale at baseline, twice during chemotherapy, and postchemotherapy.

Population screening for variant Creutzfeldt-Jakob disease using a novel blood test: diagnostic accuracy and feasibility study.

Importance: Our study indicates a prototype blood-based variant Creutzfeldt-Jakob disease (vCJD) assay has sufficient sensitivity and specificity to justify a large study comparing vCJD prevalence in the United Kingdom with a bovine spongiform encephalopathy-unexposed population. In a clinical diagnostic capacity, the assay's likelihood ratios dramatically change an individual's pretest disease odds to posttest probabilities and can confirm vCJD infection.

Objectives: To determine the diagnostic accuracy of a prototype blood test for vCJD and hence its suitability for clinical use and for screening prion-exposed populations.

Effects of exercise dose and type on sleep quality in breast cancer patients receiving chemotherapy: a multicenter randomized trial.

To examine the effects of different doses and types of exercise on sleep quality in breast cancer patients receiving chemotherapy. A multicenter trial in Canada randomized 301 breast cancer patients between 2008 and 2011 to thrice weekly, supervised exercise during chemotherapy consisting of either a standard dose of 25-30 min of aerobic exercise (STAN; n = 96), a higher dose of 50-60 min of aerobic exercise (HIGH; n = 101), or a combined dose of 50-60 min of aerobic and resistance exercise (COMB; n = 104). The secondary sleep outcomes in the trial were assessed by the Pittsburgh Sleep Quality Index (PSQI) at baseline, twice during chemotherapy, and postchemotherapy.

Utility of 3-dimensional echocardiography, global longitudinal strain, and exercise stress echocardiography to detect cardiac dysfunction in breast cancer patients treated with doxorubicin-containing adjuvant therapy.

Conventional resting left ventricular ejection fraction (LVEF) assessments have limitations for detecting doxorubicin (DOX)-related cardiac dysfunction. Novel resting echocardiographic parameters, including 3-dimensional echocardiography (3DE) and global longitudinal strain (GLS), have potential for early identification of chemotherapy-related myocardial injury. Exercise "stress" is an established method to uncover impairments in cardiac function but has received limited attention in the adult oncology setting.

A machine learned classifier that uses gene expression data to accurately predict estrogen receptor status.

Background: Selecting the appropriate treatment for breast cancer requires accurately determining the estrogen receptor (ER) status of the tumor. However, the standard for determining this status, immunohistochemical analysis of formalin-fixed paraffin embedded samples, suffers from numerous technical and reproducibility issues. Assessment of ER-status based on RNA expression can provide more objective, quantitative and reproducible test results.

Breast cancer prediction using genome wide single nucleotide polymorphism data.

Background: This paper introduces and applies a genome wide predictive study to learn a model that predicts whether a new subject will develop breast cancer or not, based on her SNP profile.

Results: We first genotyped 696 female subjects (348 breast cancer cases and 348 apparently healthy controls), predominantly of Caucasian origin from Alberta, Canada using Affymetrix Human SNP 6.0 arrays.

Pancreatic cancer hENT1 expression and survival from gemcitabine in patients from the ESPAC-3 trial.

Background: Human equilibrative nucleoside transporter 1 (hENT1) levels in pancreatic adenocarcinoma may predict survival in patients who receive adjuvant gemcitabine after resection.

Methods: Microarrays from 434 patients randomized to chemotherapy in the ESPAC-3 trial (plus controls from ESPAC-1/3) were stained with the 10D7G2 anti-hENT1 antibody. Patients were classified as having high hENT1 expression if the mean H score for their cores was above the overall median H score (48).

Sodium channel blockade with QRS widening after an escitalopram overdose.

Introduction: Escitalopram is rarely associated with prolongation of the QTc interval; however, there are no reported cases of QRS complex widening associated with escitalopram overdose. We report a case of a patient who presented with both QRS complex widening and QTc interval prolongation after an escitalopram overdose.

Case: A 16-year-old girl presented to the emergency department after ingestion of escitalopram, tramadol/acetaminophen, and hydrocodone/acetaminophen.

Obesity and survival in operable breast cancer patients treated with adjuvant anthracyclines and taxanes according to pathological subtypes: a pooled analysis.

Introduction: Obesity is an unfavorable prognostic factor in breast cancer (BC) patients regardless of menopausal status and treatment received. However, the association between obesity and survival outcome by pathological subtype requires further clarification.

Methods: We performed a retrospective analysis including 5,683 operable BC patients enrolled in four randomized clinical trials (GEICAM/9906, GEICAM/9805, GEICAM/2003-02, and BCIRG 001) evaluating anthracyclines and taxanes as adjuvant treatments.

Effects of exercise dose and type during breast cancer chemotherapy: multicenter randomized trial.

Background: Exercise improves physical functioning and symptom management during breast cancer chemotherapy, but the effects of different doses and types of exercise are unknown.

Methods: A multicenter trial in Canada randomized 301 breast cancer patients to thrice-weekly supervised exercise during chemotherapy consisting of either a standard dose of 25 to 30 minutes of aerobic exercise (STAN; n = 96), a higher dose of 50 to 60 minutes of aerobic exercise (HIGH; n = 101), or a combined dose of 50 to 60 minutes of aerobic and resistance exercise (COMB; n = 104). The primary endpoint was physical functioning assessed by the Medical Outcomes Survey-Short Form (SF)-36.

Frequent infection of neurons by SV40 virus in SIV-infected macaque monkeys with progressive multifocal leukoencephalopathy and meningoencephalitis.

Simian virus 40 (SV40), family Polyomaviridae, in immunocompromised macaques can cause fatal demyelinating central nervous system disease analogous to progressive multifocal leukoencephalopathy caused by John Cunningham (JC) virus in immunocompromised humans. Recently, we have demonstrated that JC virus can infect cerebellar granule cell neurons and cortical pyramidal neurons in immunosuppressed people. To examine whether SV40 neuronal infection occurs spontaneously in immunosuppressed macaques, we analyzed archival brain specimens from 20 simian immunodeficiency virus-infected rhesus with AIDS and 1 cynomolgus post-transplant selected with SV40 brain infection from archival records from 1991 to 2012.

Can diabetes be surgically cured? Long-term metabolic effects of bariatric surgery in obese patients with type 2 diabetes mellitus.

Objective: Evaluate the long-term effects of bariatric surgery on type 2 diabetes (T2DM) remission and metabolic risk factors.

Background: Although the impressive antidiabetic effects of bariatric surgery have been shown in short- and medium-term studies, the durability of these effects is uncertain. Specifically, long-term remission rates following bariatric surgery are largely unknown.

Adjuvant bevacizumab-containing therapy in triple-negative breast cancer (BEATRICE): primary results of a randomised, phase 3 trial.

Background: The addition of bevacizumab to chemotherapy improves progression-free survival in metastatic breast cancer and pathological complete response rates in the neoadjuvant setting. Micrometastases are dependent on angiogenesis, suggesting that patients might benefit from anti-angiogenic strategies in the adjuvant setting. We therefore assessed the addition of bevacizumab to chemotherapy in the adjuvant setting for women with triple-negative breast cancer.

Quantitative proteomic analysis of HER2 normal and overexpressing MCF-7 breast cancer cells revealed proteomic changes accompanied with HER2 gene amplification.

Unlabelled: Molecular classification of breast cancer is based, in part, on the presence or absence of amplification of the human epidermal growth factor receptor 2 (ERBB2) gene, which leads to HER2 protein overproduction. While the presence of the overexpressed HER2 protein is a necessary precondition for sensitivity to anti-HER2 therapies, many patients develop resistance. Thus, identification of the downstream effectors of this pathway will help in understanding mechanism(s) of chemoresistance and further, the identified molecules themselves may have the potential to be used as therapeutic targets.

Expression of nucleoside transporters and deoxycytidine kinase proteins in muscle invasive urothelial carcinoma of the bladder: correlation with pathological response to neoadjuvant platinum/gemcitabine combination chemotherapy.

Purpose: In pancreatic cancer, deoxycytidine kinase and the human equilibrative nucleoside transporter 1 have been validated as predictive markers for benefit from gemcitabine therapy. Gemcitabine is used with cisplatin or carboplatin as neoadjuvant chemotherapy for muscle invasive urothelial cancer of the bladder before radical cystectomy and patients rendered disease-free at surgery tend to have better outcomes. In this trial we examined if nucleoside transporter or deoxycytidine kinase protein abundance in biopsy specimens before chemotherapy is related to the response to neoadjuvant chemotherapy.

Health-related quality of life with adjuvant docetaxel- and trastuzumab-based regimens in patients with node-positive and high-risk node-negative, HER2-positive early breast cancer: results from the BCIRG 006 Study.

Background: This study aims to describe and compare health-related quality of life (HRQL) in patients with node-positive and high-risk node-negative HER2-positive early breast cancer receiving adjuvant docetaxel and trastuzumab-based or docetaxel-based regimens alone.

Methods: Eligible patients (n = 3,222) were randomly assigned to either four cycles of adjuvant doxorubicin and cyclophosphamide followed by four cycles of docetaxel (AC→T) or one of two trastuzumab-containing regimens: adjuvant doxorubicin and cyclophosphamide followed by docetaxel plus trastuzumab administered for 1 year (AC→TH) or six cycles of docetaxel plus carboplatin combined with trastuzumab administered for 1 year (TCH). The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and BR-23 were administered at baseline, the start of cycle 4 (mid), and the end of chemotherapy (EOC), as well as at 6, 12, and 24 months after chemotherapy.

Assessing SNP-SNP interactions among DNA repair, modification and metabolism related pathway genes in breast cancer susceptibility.

Genome-wide association studies (GWASs) have identified low-penetrance common variants (i.e., single nucleotide polymorphisms, SNPs) associated with breast cancer susceptibility.

Identification of a breast cancer susceptibility locus at 4q31.22 using a genome-wide association study paradigm.

More than 40 single nucleotide polymorphisms (SNPs) for breast cancer susceptibility were identified by genome-wide association studies (GWASs). However, additional SNPs likely contribute to breast cancer susceptibility and overall genetic risk, prompting this investigation for additional variants. Six putative breast cancer susceptibility SNPs identified in a two-stage GWAS that we reported earlier were replicated in a follow-up stage 3 study using an independent set of breast cancer cases and controls from Canada, with an overall cumulative sample size of 7,219 subjects across all three stages.

Plakoglobin interacts with the transcription factor p53 and regulates the expression of 14-3-3σ.

Plakoglobin (γ-catenin), a constituent of the adherens junction and desmosomes, has signaling capabilities typically associated with tumor/metastasis suppression through mechanisms that remain undefined. To determine the role of plakoglobin during tumorigenesis and metastasis, we expressed plakoglobin in human tongue squamous cell carcinoma (SCC9) cells and compared the mRNA profiles of parental SCC9 cells and their plakoglobin-expressing transfectants (SCC9-PG). We detected several p53-target genes whose levels were altered upon plakoglobin expression.

ETHNOPRED: a novel machine learning method for accurate continental and sub-continental ancestry identification and population stratification correction.

Background: Population stratification is a systematic difference in allele frequencies between subpopulations. This can lead to spurious association findings in the case-control genome wide association studies (GWASs) used to identify single nucleotide polymorphisms (SNPs) associated with disease-linked phenotypes. Methods such as self-declared ancestry, ancestry informative markers, genomic control, structured association, and principal component analysis are used to assess and correct population stratification but each has limitations.

Isolation of a calcium-binding protein of the acrosomal membrane of bovine spermatozoa.

The mammalian sperm acrosome reaction is a calcium-dependent exocytotic event characterized by extensive fusion between the plasma and the outer acrosomal membrane. The mechanisms by which elevation of cytosolic calcium initiates the membrane fusion process are not understood and the present study was undertaken to identify calcium-binding proteins in the acrosomal membrane (AM) of bovine spermatozoa. Sperm heads, purified from sonicated spermatozoa, were used to isolate an acrosomal membrane-enriched fraction on Percoll density gradients.

Germline DNA copy number aberrations identified as potential prognostic factors for breast cancer recurrence.

Breast cancer recurrence (BCR) is a common treatment outcome despite curative-intent primary treatment of non-metastatic breast cancer. Currently used prognostic and predictive factors utilize tumor-based markers, and are not optimal determinants of risk of BCR. Germline-based copy number aberrations (CNAs) have not been evaluated as determinants of predisposition to experience BCR.