Good viruses, bad viruses, biomarkers and protein structures in this week’s research highlights…
Biomarker for Hodgkin’s Lymphoma Subset: Using a high-throughput genomic approach to associate gene expression profile with treatment outcomes for Hodgkin lymphoma, researchers identified an overexpression of genes typically expressed by macrophages in samples from patients who had experienced a relapse after treatment. This was confirmed histologically by looking at stained tissue samples and tallying the number of macrophages – high numbers of macrophages are associated with treatment resistance in Hodgkin lymphoma. About 25% of patients fall into this category where a biomarker test could shuttle them into a more aggressive or experimental treatment option and may prevent them from being exposed to the side effects of primary treatments that are likely to fail. The study, led by B.C. Cancer Agency researcher Dr. Randy Gascoyne, is reported in The New England Journal of Medicine with an editorial that is touting this as the “breakthrough we have been looking for.”
Immune System Boost for HIV Patients: A very important molecular discovery may give a boost to restoring immune function in HIV infected patients. Renowned HIV scientist, Dr. Rafick-Pierre Sékaly, and his cross-border research teams at the Université de Montréal and Vaccine and Gene Therapy Institute of Florida identified that the protein PD-1 is up-regulated by the release of bacterial products from the gut. Another factor, IL-10, is subsequently increased and together this is what shuts down the CD4+ T-cell immune system in HIV patients. Therefore, the scientists suggest that new immunotherapies should aim to block PD-1 and IL-10 to help restore the debilitated immune system in HIV infected patients. The research article appears in this week’s Nature Medicine.
Not All Viruses are Bad: The ubiquitous reovirus has oncolytic actions against different types of cancer when used as a therapeutic approach. Now, prostate cancer may be added to the growing list of cancers, which includes ovarian, breast, pancreatic and gliomas, that may be treated with a reovirus based strategy. In fact, the Calgary-based Oncolytics Biotech Inc. technology platform and pipeline are based on the reovirus and contributed to the prostate study. In the prostate cancer clinical study, a viral concoction was injected into prostate cancer nodules and three weeks later, the prostates were resected. There was evidence of cancer cell death and overall, the procedure was deemed safe with only mild side effects experienced by the patients. The success of this pilot study should draw interest to expand the clinical trial novel treatment for prostate cancer. Dr. Donald Morris led the research and medical team at the University of Calgary and reports the study in Cancer Research.
Having Fun with Names: This study provides more molecular and structural details than you probably need to know but I want to point out the cool protein domain name: Really Interesting New Gene or RING domain. It is an important component of a group of proteins that regulate the potent oncogene called eIF4E (eukaryotic translation initiation factor). The details of the Université de Montréal study are described in the Proceedings of the National Academy of Sciences.
Pump It Up: Another structural study that I want to point out because of its importance: the V-ATPase. This is a membrane proton pump that controls the acidity of the cellular environment and can play critical roles for the cell in promoting a diseased state. SickKids Research Instiute scientist, Dr. John Rubinstein explains “In some types of cancer, the pumps are “hijacked” to acidify the external environment of tumours, allowing the cancer to invade surrounding tissues and spread throughout the body. The cells that take up bone minerals also use V-ATPases to dissolve bone, a process that must be limited in treating osteoporosis.” More details on the study are found here in the Proceedings of the National Academy of Sciences.
Paradoxical Signalling Interaction: The phosphatidylinositol 3-kinase (PI3K) signaling pathway is a well studied signaling module and its aberrant activity is implicated in a number of diseases including cancer. It is also the target of a handful of therapeutic drugs currently under study or in trials. However, the new study led by Dr. Deborah Anderson at the Saskatchewan Cancer Agency throws a new twist into the pathway. Their data identifies a paradoxical interaction between the p85 regulatory subunit of PI3K and the PTEN phosphatase enzyme since these two enzymes have opposing actions. This is certainly food for thought for researchers in this field to rethink their signalling models. A recent news article headlines this study as the “on switch” for cancer cell growth but it is really a much more complicated puzzle than that. The data is presented in the early edition of the Proceedings of the National Academy of Sciences.