14^th Global Biomarkers Summit October18-19,2018 | Amsterdam, Netherlands

Biography:

Xiao Wang is a researcher in Center for Primary Health Care Research (CPF), Lund University. Her research interests are different biomarkers (miRNA, Mitochondrial DNA and telomere length) associated with the pathogenesis of chronic diseases, such as venous thromboembolism (VTE), diabetes and mental disorders. Xiao Wang has found for example, miR-424-5p are associated with deep-vein thrombosis (DVT) and markers of hypercoagulability. In a recent study, the potential association between miRNAs and recurrent VTE was investigated. Her findings have been published in the journals of Thromb Haemost, Clin Epigenetics and Int J Neuropsychopharmacol et.al.

Abstract:

Patients with unprovoked first venous thromboembolism (VTE) are at a high risk of recurrence. Although circulating microRNAs (miRNAs) have been recently found to be associated with deep vein thrombosis and markers of hypercoagulability, this study is the first to examine whether circulating miRNAs are associated with the risk of VTE recurrence. A nested case-control study design was used, where plasma samples were obtained from 78 patients with unprovoked VTE from the Malmö thrombophilia study (MATS). A total of 39 VTE patients with recurrent VTE (cases) were matched with 39 VTE patients without recurrent VTE from the MATS study population by age and gender (controls). Plasma levels of 179 different miRNAs were evaluated in the 78 sample (after stop of anticoagulant treatment) using qPCR. A total of 110 miRNAs were detected throughout all samples. Among those, 15 miRNAs were found to be associated with recurrent VTE after adjusting for multiple comparisons. The highest odds ratio was found for miR-15b-5p (OR=7.8 per standard deviation increment) using conditional logistic regression. The following miRNAs, miR-15b-5p, miR-197-3p, miR-27b-3p and miR-30c-5p, exhibited a trend over time, with larger difference in miRNAs levels between cases and controls for earlier recurrence. Of these 15 miRNAs, eight miRNAs were correlated with TGFβ1/2 expression in the blood. None of them correlated with primary VTE. The findings indicate that circulating miRNAs are novel biomarkers for especially early VTE recurrence. Some of these miRNAs are involved in the regulation of platelets, coagulation, and TGFβ-pathway, which suggest that these pathways might be of importance in recurrent VTE.

Biography:

Marjut Niinivirta is an Oncologist working at the Uppsala University Hospital in Sweden and pursuing PhD at Uppsala University, researching on predictive markers in renal cell cancer.

Abstract:

Patients with metastatic renal cell cancer (mRCC) are commonly treated with the tyrosine kinase inhibitors (TKI) sunitinib and sorafenib. No predictive marker is available to select patients who will gain from these treatments. Tumoral pyruvate kinase L/R (PKLR) is a membrane protein with highly specific expression in the renal tubule. We have previously shown that the tumoral expression of cubilin is associated with progression free survival (PFS) in mRCC patients treated with sunitinib and sorafenib and in the present study; we investigated if PKLR can predict response in these patients. The expression of PKLR was analyzed in tumor tissue from a cohort of patients with mRCC (n=139) using immunohistochemistry. One hundred and thirty-six (136) of these patients were treated with sunitinib or sorafenib in the first or second-line setting. Thirty were censored because of early toxicity leading to the termination of treatment. The remaining patients (n=106) were selected for the current study. Fifty-five (52%) of the tumors expressed membranous PKLR. Patients with PKLR tumor expression experienced a significantly longer PFS compared to patients with no expression (eight vs. five months, p=0.019). In addition, the combined expression of PKLR and cubilin resulted in a higher predictive value than PKLR alone. We show that tumoral PKLR membrane expression is a positive predictive biomarker for sunitinib and sorafenib treatment in patients suffering from mRCC. Our results also indicate that the combined expression with cubilin more accurately than PKLR alone can select patients with no benefit from treatment.

Biography:

Beata Burzynska has completed her PhD from Warsaw University of Life Sciences, Poland. She is a PI at the Department of Genetics, Institute of Biochemistry and Biophysics, Polish Academy of Sciences. She conducted Post-doctoral Training at the Louisiana State University Health Sciences Center. She has published more than 40 papers in SCI journals and has been serving as a Board Member of the Committee on Biotechnology, Polish Academy of Sciences. 

Abstract:

Biography:

David G Ostrow is an MSTP graduate from the University of Chicago and is triple Board Certified in Psychiatry, Addiction and Cannabinoid Medicine. He is the Co-Founder of the American Academy of Cannabinoid Medicine, Research Director of the International Cannabis Cancer Treatment Institute, and Clinical Director of VALEO Programs for LGBTQ Persons of Chicago Lakeshore Hospital.

Abstract:

In trans-membrane signaling, interactions between agonists and their receptors cause a cascade of effects. Since phytocannabinoids contain many active ligands, and the internal endocannabinoid system has multiple receptors linked to a variety of secondary messengers, these complex mixtures can have widely varied effects based on the ratios of cannabinoid molecules, their routes of administration and the specific cells and organs targeted. Thus, the use of biomarkers has the potential to clarify the pathophysiology of the condition or symptom being treated and the mechanism(s) by which cannabinoids restore homeostasis and health. We present an extensive review of findings on six major receptors with high affinity for (Endo) cannabinoid molecules that demonstrate the common pathways and secondary feedback loops that shift MAPK signaling, cause changes in biomarkers, and restore cellular functions and homeostasis: CB1, CB2, PPARg, GPR18 and 55, and TRPV1 are covered. In both animal and in vitro studies, it was found that the cannabinoid receptors (CB1 and CB2) and GPR18 and 55 function antagonistically due to co-expression on the surface of cells. GPR18 is co-located with CB1 and GPR55 with CB2. Later, along with increased levels of lysophosphatidylinositol (LPI), itself being a membrane biomarker for decreased survival in multiple cancers. Agonist binding to both CB receptors inhibits adenylyl cyclase, halting the MAPK pathway, thereby limiting cancer cell migration and metastasis; stimulation of GPR receptors does the opposite. CB2 mediated responses reduce inflammatory markers such as IL-2, TNFa, and neutrophilia: its associated GPR55 has opposite effects. GPR18 agonist improves cardiac function and reduces markers of cardiomyopathy, as well as promoting the destruction of infectious agents. Autism is associated with mutations of the CB1 receptor and GPRs. Effects at PPARg were found to reduce glial cell activation and halt the production of fibrillary tangles and the resulting formation of amyloid beta plaques causing Alzheimer’s. Conventional diabetes medicines act at this receptor as well, possibly explaining the association seen between diabetes, insulin resistance and early onset AD. TRPV activation by cannabinoids was found to promote apoptosis of cancer cells by inactivation of the MAPK pathway and activation of caspases. In the case of capsaicin activation, influx of calcium through opening of Ca+ channels occur in contrast to cannabinoid binding. This produces an endogenous entourage effect through increased levels of anandamide and its co-synthesized analogues OEA and PEA. CB1 activation in the CNS produces a similar entourage of lipid biosynthesis that regulates glutamate and GABA neurotransmission. These encouraging results from in vitro and rodent models are beginning to be translated into controlled human trials of cannabinoid treatment of Alzheimer's, CVD, cancer, chronic pain, and autism that utilize appropriate biomarker measures to supplement the long-term clinical endpoints of chronic disease.

Biography:

Vincent Van Ginneken has completed his first PhD from Leiden University in Mathematics and Natural Sciences followed by Post-doctoral studies resulting in a second PhD at Wageningen University and Research in Agricultural Sciences. He is the Scientific Director of Blue-Green Technologies, a think-tank organization with several disciplines: biomedical, agricultural and seaweed biotechnology. He has published more than 115 papers in reputed journals like Nature and has been serving as an Editorial Board Member of some of these reputed journals. Presently, he is involved as Researcher on lipidomics based cancer/tumor research following a systems biology approach in Erasmus Medical Centre Rotterdam, Netherlands.

Abstract:

This lipidomics study was designed to find via a high-fat (HF) diet induced insulin resistant (IR) and/or type-2 diabetes (T2DM) C57Bl/6 mouse model potential novel biomarkers. Major aiming was to find following this lipidomics based approach novel safe biomarkers applicable for humans with IR/T2DM that can be used in the assessment of diagnosis, intensive treatment, clinical use and new drug development. In addition, the biomarker has to be found in blood-plasma simultaneously while it is not a component of the HF-diet. Reversed phase liquid chromatography coupled to mass spectrometry (LCMS) were used to quantify and qualify the rearrangement and repartitioning of fat stores in the heart, hind limb, carcass muscle, liver, brain and blood plasma of this mice model following a systems biology lipidomics based approach. Two potential biomarkers were found for this HF-diet mouse model. The first biomarker was a 20:3 cholesteryl-ester (20:3-ChE) which significantly increased (P≤0.016) in the fatty heart with 1317% while it rose very significantly (P≤0.00001) in blood plasma with 1013% in the HF diet group in comparison to the control-group (Co). The second biomarker was a 36:1 phosphatidylcholine (36:1-PC), which rose significantly (P≤0.025) mainly in heart muscle with 400% while concentrations increased significantly strongly (P≤0.002) in blood plasma with 1493% in the high-fat diet vs. Co. As an earlier defined prerequisite, both compounds were not found in the food. The 20:3-ChE biomarker (dihomo-γ-linolenic; 20:3 n-6) has been classified as a potential type 2 diabetes biomarker (T2DM) in a human cohort of the Uppsala Longitudinal Study of Adult Men (ULSAM). In addition, we give a biochemical explanation for the 36:1-PC as hypoxic biomarker for cardiovascular diseases (CVD) diagnosis and therapy. Both biomarkers are interesting candidates for further validation in human cohorts.

Biography:

David G Ostrow is the Founding PI of the Chicago Multicenter AIDS Cohort Study (MACS) and the Clinical Director of the Valeo program for LGBTQ persons at Chicago Lakeshore Hospital.

Abstract:

While T4 lymphocytes are considered the ultimate target of HIV infection and their depletion by transformation into factories for the replication of HIV virions leading to immune deficiency (AIDS), there are actually complexes, orchestra of cells beginning with macrophages and including B lymphocytes that are essential for the establishment of HIV infection. The cannabinoid CB2 receptors present on the surface of macrophages play an essential role in limiting the establishment of primary HIV infection of the immune system. Activation of CB2r reduces interferon-gamma production of interleukins 2,10,12, and 23 and interferon-gamma itself by way of activating the ERK 1/2 and JNK pathway in CD4+ and CD8+ T cells. This also shifts immunity from TH1 to TH2. CB2r is highly expressed in B cells and it negatively regulates differentiation and proliferation through the same pathways, limiting the expression of other lymphocyte cell surface markers. Theoretically, such actions should accelerate progression of immunosuppression in HIV+ patients. Paradoxically, CB2 agonist has been shown in vitro and in animal models to reduce the expression of the G-protein coupled chemokine receptors CD4, CXCR4 and CCR5, all of which play complementary roles in HIV binding and entry into T4 lymphocytes, directly suppressing replication of HIV. In HIV infected monocytes and macrophages, a pro-survival gene expression shift has been found that upregulates the p53/ras MAPK pathway as well as pro-inflammatory cytokine production, both of which go hand in hand in the regulatory scheme of the cannabinoid system. Thus, activation of the ERK1/2, JNK and cJun/Fos pro-apoptotic pathways via CB2r agonist acts in vitro to counter both the pro-inflammatory and anti-apoptotic effects of HIV infected immune cells as well as shield against further infection. Longitudinal studies of newly infected persons provide support for the protective effects of cannabinoid use in both the spread of HIV by sexual contact and the progression of immunodeficiency. With the widespread end of cannabis prohibition and the development of standardized laboratory measures of both blood levels of active cannabinoids and the immune biomarkers reflecting the entourage of cannabinoid effects on the orchestration of human immunological functioning and regulation, the stage is now set for the development of cannabinoid-based preventive and therapeutic treatments against HIV.