Methods to monitor the influence and potentially modulate the stromal conditioning of cancer, offers new avenues for diagnosis, personalized medicine, and therapeutic modalities.
Methods to monitor the influence and potentially modulate the stromal conditioning of cancer, offers new avenues for diagnosis, personalized medicine, and therapeutic modalities.
MONMOUTH JUNCTION, NJ, October 9, 2019 – Dr. Ingrid Verhamme from Vanderbilt University presented a poster, co-authored and in collaboration with Biotech Support Group, describing the loss of functional activity involving 2 major serum proteins, and the potential consequences of such loss in the progression of cancer. The poster was presented at The Serpins2019 Conference, September 19-22, 2019 in Sevilla, Spain, and entitled “Loss of Functional Alpha-1-Antitrypsin and Heparin Cofactor II in Inflammation and Cancer”. Authors were: Ingrid M. Verhamme, Vanderbilt University Medical Center; Nashville TN, Swapan Roy, Sowmya Avadhani, Matthew Kuruc, Biotech Support Group LLC, Monmouth Junction NJ.
Highlighting the importance of this poster report, Dr. Verhamme states that “Our hypothesis is that there may be a common host systemic response to many forms of cancer, regardless of primary tumor, stage or development of metastatic disease. This response is proposed to involve interconnected pathways attributable to thrombo-inflammation and innate immunity. All these pathways are activated by proteolysis and regulated by protease inhibition. So it is therefore likely that tumorigenesis can systemically be characterized by chronic exhaustion of inhibitory active serpins, and resulting increased protease activity. Our results support such a net decrease in inhibitory active Serpin D1, otherwise known as Heparin Cofactor II. We believe this is a very important discovery as it brings to light a potential new cancer therapeutic strategy, to selectively inhibit Thrombin in the extravascular space, as 60% of Heparin Cofactor II is extra-vascular.”
The poster describes that in various cancer types, blood serum levels of serpins have been reported as altered. Significantly however, is that in these reports, concentrations were measured by immunological methods (ELISA) rather than by functional activity. This can lead to egregiously misleading interpretation of a host’s systemic response to cancer, as the immunological assay measures in aggregate both the intact and cleaved serpin forms. In contrast to these methods, we demonstrate that with albumin depleted (AlbuVoid™) serum samples, combined with LC-MS/MS, there is potential of distinguishing between active and cleaved subpopulations of Serpins. Cleaved serpins are the product of the substrate pathway in the bifurcated serpin suicidal mechanism, which can become more pronounced due to serpin mutations or changes in the micro-environment.
This study considers that micro-environmental changes in tumors are sufficient to distort the ratio of cleaved serpin forms from intact serpin forms, and that these ratios are sufficiently differentiated so as to be reportable in the general blood circulation. Serpins A1 (Alpha-1-Antitrypsin) and D1 (Heparin Cofactor II) primarily regulate the activities of the inflammatory proteases elastase and thrombin respectively. Using functional enzyme assays, preliminary results correlate to LC-MS/MS results, confirming a significant increase in the cleaved/total ratio in cancer sera, corresponding to a net decrease in inhibitory active serpin, relative to a normal/healthy status.
Swapan Roy, Ph.D., President and Founder of Biotech Support Group, concurs stating “These are very exciting developments as methods to monitor the influence of SERPINs is a fundamentally new way to think about the microenvironment componentry of cancer. Through our academic collaborators, we continue to generate evidence that there is a fundamental dysregulation of protease inhibition in tumors that supports the host’s stromal conditioning. With that re-education comes the allowance for cancer to survive and metastasize. Most importantly, these same systemic responses which are derived from tumor tissue vasculature now can be monitored using liquid biopsies. From this, new avenues for diagnosis, personalized medicine, and therapeutic modalities are possible. Our next goal is for rigorous investigations to characterize progressive disease or response to therapies with partners and collaborators. This will be our next step towards our ultimate goal of validating biomarkers useful in the clinic. We welcome inquiries to commercialize our patent pending biomarkers, called Stroma Liquid Biopsy™, for the many different applications it can serve including early detection, wellness and risk factor monitoring, oncology drug development and personalized therapy decisions.”
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About Biotech Support Group LLC
Converging with cultural and technological disruptions forthcoming in healthcare, Biotech Support Group develops methods for cost effective and efficient sample prep essential for these expanding markets. Following a tiered business strategy, the company continues its growth in the consumable research products area supporting the rapidly expanding installation of LC-MS instrument and computational infrastructure. For this market, key products include: AlbuVoid™ and AlbuSorb™ for albumin depletion, Cleanascite™ for lipid adsorption, HemogloBind™ and HemoVoid™ for hemoglobin removal, and NuGel™ for functional proteomics. From these innovations, the company has acquired knowledgebase and biomarker intellectual property assets that support discoveries of protein markers from blood, with special emphasis on early detection and personalized medical decisions for cancer patients. For more information, go to http://www.
