July 2012 — First-in-Human Trial of a STAT-3 Selective Inhibitor for Cancer Therapy
There has been evidence that signal transducer and activator of transcription-3 (STAT-3) is increased in cancers, where it drives cell transformation, tumor progression, and resistance to therapy. While STAT-3 is therefore considered a highly attractive therapeutic target, it has long been regarded as "undruggable."
Recently published in the new AACR journal Cancer Discovery, researchers at the University of Pittsburgh and collaborators have developed a new strategy to block STAT-3 in cancers. Specifically, they developed a STAT-3 decoy oligonucleotide that effectively decreased levels of STAT-3 target genes in head and neck tumors in a phase 0 trial. Through chemical modification, the team enhanced the stability of this molecule to enable systemic delivery of the drug in patients.
Watch Jennifer Grandis, MD, FACS, Professor of Otolaryngology at the University of Pittsburgh School of Medicine, and Leader of the Head and Neck Cancer Program at UPCI, discuss the study and its results:
July 2012 — Flexible Sigmoidoscopy Screening Reduces Colorectal Cancer Incidence and Mortality
A new study of the multicenter Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial evaluated the effect of colorectal cancer screening by flexible sigmoidoscopy in comparison with usual care. Results of this large randomized trial indicate that screening with flexible sigmoidoscopy was associated with a 26% reduction in overall colorectal cancer mortality and a 21% reduction in the incidence of colorectal cancer.
Watch Robert Schoen, MD, MPH, Professor of Medicine and Epidemiology at the University of Pittsburgh, and lead author of the study, discuss these results that were recently published in the New England Journal of Medicine:
April 2012 — Chemoprevention Studies Uncover Cancer-Inhibitory Mechanisms of Dietary Constituents
While population-based studies have demonstrated that people who eat a diet rich in fruits and vegetables have a lower risk of developing cancer, scientists are now beginning to uncover the specific dietary components responsible and their mechanisms of action. Recently, UPCI researchers discovered that the broccoli constituent analogue D,L-sulforaphane (SFN), a promising cancer chemopreventive agent, can induce cell death through a mechanism involving PKCβ-mediated phosphorylation of the p66Shc adaptor protein. In addition, the research team demonstrated that benzyl isothiocynate (BITC), a constituent of edible cruciferous vegetables, can induce breast cancer and colon cancer cell death through a PUMA-dependent mechanism.
These studies were recently published in the Journal of Cellular Biochemistry and PLoS One.
Watch Shivendra Singh, PhD, Associate Director of Basic Research at UPCI and Professor of Pharmacology & Chemical Biology at the University of Pittsburgh, discuss his recent findings:
April 2012 — Genomic Analysis of Kidney Cancers Reveal Shared Tumor Type-Specific Copy Number Variations
In a collaborative research study, investigators at UPCI characterized several diagnostic subtypes of renal cell cancers based on the distribution of copy number variants (CNV) both within and across tumors spanning the entire genome. They found that despite immense genomic heterogeneity, distinct CNV segments were common within each of 4 tumor subclassifications. The subset of shared genomic amplifications or deletions that were identified for each subclassification could provide critical diagnostic or prognostic biomarkers of renal cell cancers.
This study was recently published in the American Journal of Pathology.
Watch William LaFramboise, PhD, Co-Director of the UPCI Cancer Biomarkers Facility and Associate Professor of Pathology; and Rajiv Dhir, MD, Medical Director of UPCI Tissue and Research Pathology Services and Chief of Pathology at UPMC Shadyside Hospital, discuss their collaborative work:
April 2012 — UPCI Researchers Gain Better Understanding of Radiation-Mitigator Drug
According to a UPCI/University of Pittsburgh School of Medicine study, researchers may have a better way of understanding how a drug used to protect against and mitigate irradiation damage interacts inside human cells. The study involved the successful labeling and tracking of JP4-039, a drug that combats irradiation-induced cell death by assisting the mitochondria.
Results of the study will be presented at the AACR Annual Meeting in Chicago.
Watch Joel Greenberger, MD, Chairman of Radiation Oncology at UPCI and Professor of Radiation Oncology at the University of Pittsburgh School of Medicine, discuss the study findings:
