On April 21, 2016 OncoCyte Corporation (NYSE MKT:OCX), a developer of novel, non-invasive blood based tests for the early detection of cancer, reported that its bladder cancer abstract has been selected for presentation in a poster session, including a live panel discussion on the results, at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting to be held in Chicago, Illinois June 3rd through the 7th (Press release, BioTime, APR 21, 2016, View Source;p=RssLanding&cat=news&id=2159019 [SID:1234511206]).

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The Company has been developing a urine-based diagnostic that could be more effectively used for screening for bladder cancer in patients presenting with hematuria, confirming indeterminate cytology findings, and diagnosing recurrence of bladder cancer in patients in remission. OncoCyte presented interim clinical study data for the non-invasive detection of bladder cancer at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) in April of 2015 demonstrating a high level of sensitivity and specificity in the detection of urothelial carcinoma, the most common type of bladder cancer. At AACR (Free AACR Whitepaper) OncoCyte reported a ROC AUC of .91, sensitivity of 90% and specificity of 83%. The study to be presented at ASCO (Free ASCO Whitepaper) continued the development of the diagnostic first reported in the 2015 study.

"ASCO is one of the largest medical meetings of the year and OncoCyte is excited to be presenting clinical data for our diagnostics for the second year in a row," commented William Annett, Chief Executive Officer. "Our bladder test has the potential to screen approximately four million patients along the cancer spectrum annually and reflects our robust clinical pipeline of diagnostics assays. We are looking forward to sharing our results with the medical community as well as our shareholders."

The data will be presented by Karen B. Chapman, Ph.D., OncoCyte’s Vice President of Research.

Presentation Title: "Derivation of gene expression classifiers for the non-invasive detection of bladder cancer in the hematuria and recurrence surveillance populations."
Session Title: Tumor Biology
Poster Session: 1 PM – 4:30 PM June 6, 2016
Poster Discussion Session: 4:45 PM – 6 PM, June 6, 2016

About Bladder Cancer

Bladder cancer has been projected to have the highest lifetime treatment costs per patient of all cancers. Bladder cancer in the U.S. was estimated to cost $125B in 2010, growing to $155B in 2014. The high recurrence rate and ongoing invasive monitoring requirements drive the financial burden of this disease.

The prenyl-binding protein PDEδ is crucial for the plasma membrane localization of prenylated Ras. Recently, we have reported that the small-molecule Deltarasin binds to the prenyl-binding pocket of PDEδ, and impairs Ras enrichment at the plasma membrane, thereby affecting the proliferation of KRas-dependent human pancreatic ductal adenocarcinoma cell lines. Here, using structure-based compound design, we have now identified pyrazolopyridazinones as a novel, unrelated chemotype that binds to the prenyl-binding pocket of PDEδ with high affinity, thereby displacing prenylated Ras proteins in cells. Our results show that the new PDEδ inhibitor, named Deltazinone 1, is highly selective, exhibits less unspecific cytotoxicity than the previously reported Deltarasin and demonstrates a high correlation with the phenotypic effect of PDEδ knockdown in a set of human pancreatic cancer cell lines.

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Inhibition of phosphoinositide 3-kinase (PI3K) signaling is an appealing approach to treat brain tumors, especially glioblastoma multiforme (GBM). We previously disclosed our successful approach to prospectively design potent and blood-brain barrier (BBB) penetrating PI3K inhibitors. The previously disclosed molecules were ultimately deemed not suitable for clinical development due to projected poor metabolic stability in humans. We, therefore, extended our studies to identify a BBB penetrating inhibitor of PI3K that was also projected to be metabolically stable in human. These efforts required identification of a distinct scaffold for PI3K inhibitors relative to our previous efforts and ultimately resulted in the identification of GDC-0084 (16). The discovery and preclinical characterization of this molecule are described within.

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The interactions of extracellular ligands with single membrane spanning receptors, such as kinases, typically serve to agonise or antagonise the intracellular activation of signalling pathways. Within the cell, E3 ligases can act to alter the localisation and activity of proteins involved in signalling systems. Structural and functional characterisation of two closely related single membrane spanning molecules, RNF43 and ZNRF3, has recently revealed the receptor-like functionalities of a ligand-binding ectodomain combined with the intracellular architecture and activity of an E3 ligase. This direct link provides a hereto novel mechanism for extracellular control of ubiquitin ligase activity that is used for the modulation of Wnt signalling, a pathway of major importance in embryogenesis, stem cell biology and cancer. In this review we discuss recent findings for the structure and interactions of the extracellular region of RNF43/ZNRF3 and draw parallels with the properties and function of signalling receptor ectodomains.
Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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We describe the rationale and design of the ongoing randomized, active-controlled, multicenter, Phase III study evaluating the efficacy of pixantrone and rituximab versus gemcitabine and rituximab in patients with diffuse large B-cell lymphoma or follicular grade 3 lymphoma, who are ineligible for high-dose chemotherapy and stem cell transplantation, and who failed front-line regimens containing rituximab. The administration schedule is pixantrone 50 mg/m(2) intravenously (iv.) or gemcitabine 1000 mg/m(2) iv. on days 1, 8 and 15, combined with rituximab 375 mg/m(2) iv. on day 1, up to six cycles. Pixantrone has a conditional European marketing approval for monotherapy in adults with multiple relapsed or refractory aggressive B-cell non-Hodgkin lymphoma. Our trial explores the efficacy of combining pixantrone with rituximab and completes postauthorization measures.
NCT01321541.

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