10^th Annual Congress on Biomarkers, Clinical Research & Therapeutics October 03-04, 2018 Los Angeles, California, USA

Biography:

Katarína Janšáková has her expertise in molecular biology. Her PhD study was focused on oxidative stress markers in relation to various inflammatory diseases and salivary markers. Currently, she works as a post doc at Institute of Physiology, Faculty of Medicine, Comenius University in Slovakia where she participates in many projects with the team of Academic Research Center for Autism. Her primary interest is in salivary research and problems that meet using a saliva in the clinical practice. 

Abstract:

Statement of the Problem: Crohn’s disease and orofacial granulomatosis are autoimmune lifelong gradually worsening diseases. Diagnostics is a long-lasting process requiring colonoscopy and related biopsy. New screening biomarkers might assist early diagnosis and facilitate monitoring of disease activity. The aim of this study was to analyse markers of oxidative stress and antioxidative status and inflammation in saliva of patients with Crohn’s disease (CD) orofacial granulomatosis (OFG) and concurrent orofacial granulomatosis and Crohn’s disease (OFG+CD) and compare them with healthy controls (CTRL).

Methodology: Ninety-three patients were divided into individual groups according to their clinical diagnosis and healthy controls. Unstimulated whole mouth saliva was collected and markers of oxidative stress and antioxidant status were measured. Markers of inflammation, immunoglobulin A, lactoferrin and myeloperoxidase, were assessed as well.

Findings: The concentration of total salivary proteins was higher in all patients in comparison with control group. There was observed higher level of immunoglobulin A in all experimental groups compare to the control group. Salivary lactoferrin was higher in the OFG+CD group compared to the CTRL and CD groups. Analysis of antioxidant status represented by ferric reducing antioxidant power showed lower concertation in all experimental groups. On the other hand, carbonyl stress was higher in saliva of CD and OFG+CD patients. Marker of protein oxidation was higher in CD and OFG group compare to control group.

Conclusion & Significance: The results indicate that the composition of saliva is altered in CD and OFG with increased oxidative stress. The increased concentrations of immunoglobulin A and lactoferrin may be of salivary gland origin since levels of inflammatory cell derived myeloperoxidase were not significantly increased. This study suggests that saliva could have a role in monitoring CD and OFG but there is a need for further longitudinal studies focused on analysing a panel of markers in saliva of these patients.

Recent Publications (minimum 5)

1.            Aguirre A, Nugent C A (2015) Images in Clinical Medicine: Oral Manifestation of Crohn's Disease, The New England journal of medicine 373: 1250.

2.            Campbell H, Escudier M, Patel P, Nunes C, Elliott T R, Barnard K, Shirlaw P, Poate T, Cook R, Milligan P, Brostoff J, Mentzer A, Lomer M C, Challacombe S J, Sanderson J D (2011) Distinguishing orofacial granulomatosis from crohn's disease: two separate disease entities?, Inflammatory bowel diseases 17: 2109-2115.

3.            Tothova L, Kamodyova N, Cervenka T, Celec P (2015) Salivary markers of oxidative stress in oral diseases, Frontiers in cellular and infection microbiology 5: 73.

4.            Tuzun A, Erdil A, Inal V, Aydin A, Bagci S, Yesilova Z, Sayal A, Karaeren N, Dagalp K (2002) Oxidative stress and antioxidant capacity in patients with inflammatory bowel disease, Clinical biochemistry 35: 569-572.

Said H S, Suda W, Nakagome S, Chinen H, Oshima K, Kim S, Kimura R, Iraha A, Ishida H, Fujita J, Mano S, Morita H, Dohi T, Oota H, Hattori M (2014) Dysbiosis of salivary microbiota in inflammatory bowel disease and its association with oral immunological biomarkers, DNA research : an international journal for rapid publication of reports on genes and genomes

Biography:

I am a Consultant in the Department of Molecular Medicine and a member of the Mayo Clinic Cancer Center, as well as the co-director of the Biomarker Discovery Program, within the Center for Individualized Medicine. My research program consists of bioinformatics specialists, molecular biologists, epidemiologists, and pathologists. This team has demonstrated success in discovery and translation of several biomarkers as well as developing evidence-based models that should help clinicians stratify (cancer) patients in order to provide each individual with the appropriate care. With the recent advances in Next Generation Sequencing (NGS) technologies my laboratory have been engaging in massive sequencing to scan the genome of cancer cells for abnormalities that can be used for clinical purposes such as diagnosis and stratification of patients for optimal treatment. Published papers in Journal of Clinical Oncology, Cancer Research and BLOOD further demonstrate our discovery, validation, and translation capabilities.

Published and/ or presented over 100 peer reviewed publications.

Abstract:

Radical improvement in cancer care will be accomplished by individualizing patient management via the integration of genomics and functional model systems.    A process that uses comprehensive genomics to discover biomarkers will be presented and followed by a representative example. The hypothesis was that chromosomal rearrangements (CRs) could separate lowrisk of progression (LRP) from intermediate and high risk of progression (IHRP) prostate cancer (PCa). The number of abnormal junctions did not distinguish LRP from IHRP.  Loci corresponding to genes implicated in PCa were more frequently altered in IHRP.  Integrated analysis of CNVs and microarray data yielded six potential markers that were more frequently detected in the GP3 of a Gleason score 7 (GS7) PCa compared to GP3 in a GS6 PCa.  Five of those were cross-validated in an independent sample-set with statistically significant AUCs. 

Recent breakthroughs in immunotherapy and targeted therapies are now becoming cancer agnostic (i.e. NTRK inhibitors) arguing for a more individualized approach to patient care.  A process that uses that a combination of  comprehensive genomics with 3D organoid-type functional model systems to guide treatments will be presented followed by a representative example.  We tested the hypothesis in a triple negative breast cancer (TNBC) patient with metastatic.  Comprehensive genomic information derived from the patient’s tumor cells was integrated with the purpose of deciphering the activated molecular pathways in her tumor.  The results of the genomic analysis were then used to functionally validate drug sensitivity and predict response to therapy in 3D microcancer preclinical model systems grown from the patient’s tumor cells.  The patient was subsequently treated with the recommended drug  and showed a near complete response as observed by radiographic and blood-marker testing. 

Biography:

Klaudia Kyselicová has her expertise in physical anthropology. At The Academic Research Center for Autism (ARCA, Comenius University, Slovakia) she is actively seeking for biomarkers for autism spectrum disorders. Part of her research focuses on anthropometric evaluations of the autism phenotype and dactyloscopic traits of children and adults diagnosed with ASD (Autism spectrum disorders). This is one of the approaches of ARCA towards fully explaining etiopathological mechanisms of autism with direct implications on clinical care and pharmacological interventions.

Abstract:

The 2D:4D ratio (second to fourth digit ratio) is sexually dimorphic; males of different population studied so far, had  lower 2D:4D than females. It is generally assumed that the sexual dimorphism is established during early prenatal development under the influence of sex hormones and the 2D:4D ratio is supposed to remain stable after early prenatal stages. Proponents of the „extreme male brain „theory suggested that an increased androgen exposure in utero may contribute to the development of autism spectrum disorders. The aim of our study was to test whether 2D:4D is sexually dimorphic, stable and a valid biomarker for autism.

Our results showed a  significant difference (P = 0.0001) in the digit ratio of the right hand and sexual dimorphism in the expected direction – females (N = 86) had, on average, the ratio of 0.979 and males (N = 86) the ratio of 0.96 in Slovak adult population . This sexual dimorphism in 2D:4D ratio occurred even in children of the same population, in girls (N = 52) the average digit ratio was 0.957, while in boys (N = 56) the average digit ratio was 0.945. However, our findings also suggest that the 2D:4D ratio does not remain constant throughout the life span, but slowly increases in a stable manner during childhood. Very significant differences could be found in the digit ratio of Slovak boys and girls when compared to adults for both the right hand (P = 0.0031 boys, P < 0.0001 girls) and left hand (P = 0.0068 boys, P = 0.0177 girls). After testing whether this ratio correlates with the Autism quotient of adults diagnosed with Asperger’s syndrome, no correlation was assessed. Our study indicates that the 2D:4D ratio could not be a reliable biomarker for autism spectrum disorders. This study was supported by grant APVV 15-0045 and APVV 15-0085.

Recent Publications (minimum 5)

1.            Baron-Cohen S (2002) The extreme male brain theory of autism. Trends in Cognitive Sciences 6:248-254.

2.            Trivers R, Manning J, Jacobson A (2006) A longitudinal study of digit ratio (2D:4D) and other finger ratios in Jamaican children. Hormones and Behavior 49:150-156.

3.            Malas MA, Dogan S, Evcil EH, Desdicioglu K (2006) Fetal development of the hand, digits nad digits ratio (2D:4D). Early Human Development 82:469-475.

4.            Manning JT, Bundred PE, Newton DJ, Flanagan BF (2003) The second to fourth digit ratio and variation in the androgen receptor gene. Evolution and Human Behavior 24:399-405.

5. Manning JT, Stewart A, Wilson J, Lewis-Jones DI (2004) Sex and   ethnic differences in 2nd to 4th digit ratio of children. Early Human Development 80:161-168.

Biography:

Gordon Moffat has his experience if Life Sciences with an Honors in Biology with training in Radiology. His passion for science and interest in microbiology lead him to pursue and obtain a Doctor of Medicine. Currently he is working at the State University of New York Brooklyn Health Sciences Center in Internal Medicine and the forthcoming Medicine Chief Resident. His professional interests include: Medical Oncology, Hospice and Palliative Medicine, and Geriatric Medicine. He is currently working on research projects at Memorial Sloan Kettering Cancer Center in Manhattan, New York that are expected to be published. He is also a candidate for the Alpha Omega Alpha Honor Medical Society Postgraduate Fellowship Award.
 

Abstract:

Identifying mutations in breast cancer genes (BRCA1, BRCA2, PABL2) has important clinical implications on a woman's lifetime susceptibility to breast cancer development. Nearly 10% of immigrants to the United States come from the Caribbean and few studies exist that examine breast cancer gene mutations in African-Caribbean women with existing breast cancer. The purpose is to specifically describe breast cancer epidemiology statistics and review prevalence of BRCA mutations in this cohort.