Prospective Study of Cardiac Events During Proteasome Inhibitor Therapy for Relapsed Multiple Myeloma.

Purpose: Cardiovascular adverse events (CVAEs) can occur during proteasome inhibitor (PI) therapy. We conducted a prospective, observational, multi-institutional study to define risk factors and outcomes in patients with multiple myeloma (MM) receiving PIs.

Patients And Methods: Patients with relapsed MM initiating carfilzomib- or bortezomib-based therapy underwent baseline assessments and repeated assessments at regular intervals over 6 months, including cardiac biomarkers (troponin I or T, brain natriuretic peptide [BNP], and N-terminal proBNP), ECG, and echocardiography.

The combined survival effect of codon 72 polymorphisms and p53 somatic mutations in breast cancer depends on race and molecular subtype.

Background: The codon 72 polymorphism in the p53 gene relates to the risk of breast cancer (BC), but this relationship in racially diverse populations is not known. The present study examined the prognostic value of this polymorphism for African American (AA) and Caucasian (CA) BC patients separately and considered the confounding variables of molecular subtypes and somatic mutations in p53.

Methods: Tissue sections of BCs from 116 AAs and 160 CAs were evaluated for p53 mutations and genotyped for the codon 72 polymorphism.

Molecular Biomarkers of Colorectal Cancer and Cancer Disparities: Current Status and Perspective.

This review provides updates on the efforts for the development of prognostic and predictive markers in colorectal cancer based on the race/ethnicity of patients. Since the clinical consequences of genetic and molecular alterations differ with patient race and ethnicity, the usefulness of these molecular alterations as biomarkers needs to be evaluated in different racial/ethnic groups. To accomplish personalized patient care, a combined analysis of multiple molecular alterations in DNA, RNA, microRNAs (miRNAs), metabolites, and proteins in a single test is required to assess disease status in a precise way.

A comparison of 12-gene colon cancer assay gene expression in African American and Caucasian patients with stage II colon cancer.

Background: African American (AA) colon cancer patients have a worse prognosis than Caucasian (CA) colon cancer patients, however, reasons for this disparity are not well understood. To determine if tumor biology might contribute to differential prognosis, we measured recurrence risk and gene expression using the Oncotype DX® Colon Cancer Assay (12-gene assay) and compared the Recurrence Score results and gene expression profiles between AA patients and CA patients with stage II colon cancer.

Methods: We retrieved demographic, clinical, and archived tumor tissues from stage II colon cancer patients at four institutions.

Clinical Implications of Rabphillin-3A-Like Gene Alterations in Breast Cancer.

For the rabphillin-3A-like (RPH3AL) gene, a putative tumor suppressor, the clinical significance of genetic alterations in breast cancers was evaluated. DNA and RNA were extracted from formalin-fixed, paraffin-embedded (FFPE) cancers and matching normal tissues. DNA samples were assessed for loss of heterozygosity (LOH) at the 17p13.

Mining the TRAF6/p62 interactome for a selective ubiquitination motif.

A new approach is described here to predict ubiquitinated substrates of the E3 ubiquitin ligase, TRAF6, which takes into account its interaction with the scaffold protein SQSTM1/p62. A novel TRAF6 ubiquitination motif defined as [-(hydrophobic)-k-(hydrophobic)-x-x-(hydrophobic)- (polar)-(hydrophobic)-(polar)-(hydrophobic)] was identified and used to screen the TRAF6/p62 interactome composed of 155 proteins, that were either TRAF6 or p62 interactors, or a negative dataset, composed of 54 proteins with no known association to either TRAF6 or p62. NRIF (K19), TrkA (K485), TrkB (K811), TrkC (K602 and K815), NTRK2 (K828), NTRK3 (K829) and MBP (K169) were found to possess a perfect match for the amino acid consensus motif for TRAF6/p62 ubiquitination.

Defining an Embedded Code for Protein Ubiquitination.

It has been more than 30 years since the initial report of the discovery of ubiquitin as an 8.5 kDa protein of unknown function expressed universally in living cells. And still, protein modification by covalent conjugation of the ubiquitin molecule is one of the most dynamic posttranslational modifications studied in terms of biochemistry and cell physiology.

Identification of a consensus site for TRAF6/p62 polyubiquitination.

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an ubiquitin ligase that regulates a diverse array of physiological processes via forming Lys-63 linked polyubiquitin chains. In this study, the lysine selection process for TRAF6/p62 ubiquitination was examined. The protein sequence of two characterized TRAF6/p62 substrates, NRIF and TrkA, revealed a conserved consensus pattern for the ubiquitination site of these two TRAF6 substrates.

Plasma Proteome Database as a resource for proteomics research.

Plasma is one of the best studied compartments in the human body and serves as an ideal body fluid for the diagnosis of diseases. This report provides a detailed functional annotation of all the plasma proteins identified to date. In all, gene products encoded by 3778 distinct genes were annotated based on proteins previously published in the literature as plasma proteins and the identification of multiple peptides from proteins under HUPO's Plasma Proteome Project.