Analytical Validation of Cxbladder Detect, Triage, and Monitor: Assays for Detection and Management of Urothelial Carcinoma.

: Cxbladder assays are reverse transcription-quantitative polymerase chain reaction (RT-qPCR) tests incorporating five genetic biomarkers (, , , , and ) to provide risk stratification for urothelial carcinoma (UC) in patients with hematuria or undergoing surveillance for recurrent disease. This study evaluated the analytical validity of the Cxbladder Detect, Triage, and Monitor assays. Pre-specified acceptance criteria, including the assays' fundamental aspects (sample and reagent stability, RNA extraction quality, RT-qPCR linearity, and analytical sensitivity and specificity), accuracy and precision, and reproducibility between laboratories.

Discovery of AL-GDa62 as a Potential Synthetic Lethal Lead for the Treatment of Gastric Cancer.

Diffuse gastric cancer and lobular breast cancer are aggressive malignancies that are frequently associated with inactivating mutations in the tumor suppressor gene Synthetic lethal (SL) vulnerabilities arising from dysfunction represent attractive targets for drug development. Recently, SLEC-11 () emerged as a SL lead in E-cadherin-deficient cells. Here, we describe our efforts to optimize .

E-cadherin-deficient cells have synthetic lethal vulnerabilities in plasma membrane organisation, dynamics and function.

Background: The E-cadherin gene (CDH1) is frequently mutated in diffuse gastric cancer and lobular breast cancer, and germline mutations predispose to the cancer syndrome Hereditary Diffuse Gastric Cancer. We are taking a synthetic lethal approach to identify druggable vulnerabilities in CDH1-mutant cancers.

Methods: Density distributions of cell viability data from a genome-wide RNAi screen of isogenic MCF10A and MCF10A-CDH1 cells were used to identify protein classes affected by CDH1 mutation.

Genome-wide methylation analysis identifies a core set of hypermethylated genes in CIMP-H colorectal cancer.

Background: Aberrant DNA methylation profiles are a characteristic of all known cancer types, epitomized by the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC). Hypermethylation has been observed at CpG islands throughout the genome, but it is unclear which factors determine whether an individual island becomes methylated in cancer.

Methods: DNA methylation in CRC was analysed using the Illumina HumanMethylation450K array.

E-cadherin loss alters cytoskeletal organization and adhesion in non-malignant breast cells but is insufficient to induce an epithelial-mesenchymal transition.

Background: E-cadherin is an adherens junction protein that forms homophilic intercellular contacts in epithelial cells while also interacting with the intracellular cytoskeletal networks. It has roles including establishment and maintenance of cell polarity, differentiation, migration and signalling in cell proliferation pathways. Its downregulation is commonly observed in epithelial tumours and is a hallmark of the epithelial to mesenchymal transition (EMT).

A multigene urine test for the detection and stratification of bladder cancer in patients presenting with hematuria.

Purpose: We investigated whether the RNA assay uRNA® and its derivative Cxbladder® have greater sensitivity for the detection of bladder cancer than cytology, NMP22™ BladderChek™ and NMP22™ ELISA, and whether they are useful in risk stratification.

Materials And Methods: A total of 485 patients presenting with gross hematuria but without a history of urothelial cancer were recruited prospectively from 11 urology clinics in Australasia. Voided urine samples were obtained before cystoscopy.

Predicting clinical outcome through molecular profiling in stage III melanoma.

Purpose: Patients with macroscopic stage III melanoma represent a heterogeneous cohort with average 5-year overall survival rates of <30%. With current algorithms, it is not possible to predict which patients will achieve longer-term survival. We hypothesized that molecular profiling could be used to identify prognostic groups within patients with stage III melanoma while also providing a greater understanding of the biological programs underpinning these differences.

Multiple gene expression classifiers from different array platforms predict poor prognosis of colorectal cancer.

Purpose: This study aimed to develop gene classifiers to predict colorectal cancer recurrence. We investigated whether gene classifiers derived from two tumor series using different array platforms could be independently validated by application to the alternate series of patients.

Experimental Design: Colorectal tumors from New Zealand (n = 149) and Germany (n = 55) patients had a minimum follow-up of 5 years.

N-terminal E-cadherin peptides act as decoy receptors for Listeria monocytogenes.

The observation that E-cadherin is the principal epithelial receptor for the bacterial pathogen Listeria monocytogenes led us to investigate whether N-terminal fragments of E-cadherin containing the L. monocytogenes binding domain could inhibit entry of the bacteria into cultured epithelial cells. Here we demonstrate that a conditioned medium from a gastric cancer cell line (Kato III) that carries a truncating CDH-1 mutation 3' of the L.