World Cancer Research and Biomarkers Conference September 25-26, 2019 | Toronto, Canada

Biography:

I’m 80s in China which is an open-minded generation. I have a younger sister and a happy family. I got my MS degree three years ago and worked as a resident. I love research, so I chose to begin my research life at here as a visiting student. 

Abstract:

Purpose: The purpose of this work was to evaluate the effect of histone deacetylase (HDAC) inhibitor, CN133, on castration-resistance prostate cancer (CRPC) xenograft model and a possibility for quantifying this HDACi occupancy in this prostate cancer model using the HDAC PET/CT imaging probe, [¹¹C]martinostat.

Methods: In the 22Rv1 xenograft model, we designed 5 groups of 10 mice bearing 22RV1 xenografts including vehicle, 25mg/kg, 50mg/kg SAHA or 1mg/kg and 5 mg/kg cn133, and the anti-tumor efficacy of CN133 was compared to the pan-HDAC inhibitor Suberoylanilide Hydroxamic Acid (SAHA).

We imaged 3 groups of 4 mice bearing 22RV1 xenografts before and 21 d after treatment with control vehicle, 1mg/kg and 5mg/kg CN133. Uptake on pre- and post-treatment imaging was measured and compared.

We also compared the abilities of our selective HDAC inhibitor, CN133, with pan-HDAC inhibitors, SAHA, in affecting prostate cancer cell proliferation, invasion, migration. AR-mediated target gene and target protein expression were assessed in 22RV1 prostate cancer cell lines by qPCR and western blot.

Result: Treatment of 22RV1 tumor-bearing nude mice with 1mg/kg cn133 led to a 50% reduction in 

Biography:

Isao Matsuura  Institute of Molecular and Genomic Medicine, National Health Research Institutes, No.35 Keyan Road, Zhunan 350, Taiwan ,Department of Biostatistics, School of Public Health and ^c Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, 683 Hoes Lane, Piscataway, NJ 08854, USA

Abstract:

Triple-negative breast cancer (TNBC) is often aggressive and metastatic.  Transforming growth factor-b acts as a tumor-promoter in TNBC.  Smad3, a major downstream effector protein in the TGF-b signaling pathway, is regulated by phosphorylation at several sites.   The functional significance of the phosphorylation of the linker region in Smad3 is poorly understood for TNBC.  Among the four sites in the Smad3 linker region, threonine-179 (T179) appears to be unique as it serves as the binding site for multiple WW-domain-containing proteins upon phosphorylation, suggesting that this phosphorylation is a key for Smad3 to engage other pathways.

Using genome editing, we introduced for the first time a knock-in (KI) mutation in the endogenous Smad3 gene in IV2, a lung-tropic subline of the human MDA-MB-231 TNBC cell line.  In the resulting cell line, the Smad3 T179 phosphorylation site is replaced by non-phosphorylatable valine (T179V) with the mutation in both alleles.  

The T179V KI reduced cell growth rate and mammosphere formation. These phenomena were accompanied by a significant upregulation of p21^Cip1 and downregulation of c-Myc.  The T179V KI also reduced cell migration and invasion in vitro. In the mouse xenograft models, the T179V KI markedly reduced the establishment of primary tumor in the mammary fat pad and the lung metastasis.

Our results using gene editing indicate the cancer-promoting role of Smad3 T179 phosphorylation in the human TNBC cells. Our findings highly suggest that controlling this phosphorylation may have therapeutic potential for TNBC.

Biography:

Ravinder Singh is working as Associate Professor and Head Clinical Studies at Chitkara College of Pharmacy, Chitkara University, Punjab, India. He has published various papers in journals of international repute and has been serving as a reviewer of several journals. His area of speciualisation is clinical studies related to endocrine disorders. He has attended and delievered various lectures at national and international conferences.
 

Abstract:

This study concerns in the simultaneous open model clinical study of the drug named sitagliptin a potent hyperglycaemic drug against a novel entity of natural origin BGR-34 in diabetic subjects. This study comprises the randomized, parallel, comparative study in which 100 subjects were planned to include. The patients were randomly divided in two groups on the basis of Inclusion and Exclusion criteria. Total 90 patients of mean age 30-65 years with type 2 diabetes were enrolled in this study and then the data was analysed on the basis of the different test which included HbA1c (glycated haemoglobin), rbs (random blood sugar), fbs (fasting blood sugar) and ppg (postprandial glucose) values. After completion of the data calibration results were analyzed and as a result 10-20% decreased values of HBA1C values accompanied with the RBS, FBS and PPG values were seen with the patients undergoing with 12 week course of the BGR-34. The results concluded that BGR-34 is effective in the reducing high blood sugar levels and this reflects that BGR-34 therapy is more effective drug in the treatment of diabetes suggesting that it is better in efficacy, reliability and affordability with little or no adverse effects.

Biography:

Sheida Naderi-Azad has completed her Bachelor of Science in Microbial and Environmental Pathophysiology from University of British Columbia and is currently an MD Candidate at the University of Toronto Faculty of Medicine. She has an expertise in immunodermatology, with a deep interest in melanoma immunotherapeutics, primary immunodeficiency diseases such as atopic dermatitis, and autoimmune conditions such as psoriasis. She has most recently completed a summer studentship at the Melanoma Clinic, Massachusetts General Hospital. She has had numerous published articles and presentations on melanoma therapeutics, anti-inflammatory conditions and dermatologic comorbidities such as mood disorders.

Abstract:

Statement of the Problem: Advanced melanoma involves metastasis to distant sites and is associated with poor long-term survival (Fisher et al., 2012). Current treatment options for melanoma include interleukin 2, targeted therapy (BRAFi, MEKi) and immunotherapy (CTLA4 antibody, PD1/PDL1 antibody). While targeted therapeutics can successfully block oncogenic signaling with high clinical response, they result in high relapse rates due to acquired resistance. Furthermore, while immunotherapeutics can induce durable responses, they have lower response rates due to immune evasion and suppression of effector function in tumour microenvironment. The purpose of this study is to discuss the potential for combining immunotherapy and targeted therapy with the goal of achieving high response rates with prolonged duration. Methodology & Theoretical Orientation: To obtain these results, various search terms such as immunotherapy and targeted therapy were utilized. Furthermore, the articles were selected based on recency of publication as well as depth of detail regarding the specific immunologic mechanisms by which combination therapies exert their effects. Findings: The results show that potential mechanisms of combinatorial activity of immunotherapy and targeted therapy include increasing antigen presentation, as well as improved lymphocyte homing and function. Yet it is important to note that long-term consequences of combinatorial therapeutics are uncertain, and clinical trials of combinations have resulted in adverse effects such as hepatotoxicity and intestinal perforation. Conclusion & Significance: Altogether, these results indicate a potential combination for BRAF-targeted therapy and immunotherapy in achieving long-term durable responses.

Biography:

Eleanor Cawthorne undertook her undergraduate degree in Biochemistry with a Research Placement at The University of Huddersfield in 2012. During her time at Huddersfield she was awarded a placement year at the University of Leeds in the Leeds Institute of Cardiovascular and Metabolic Medicine. Here she worked under supervisor Dr. Richard Pease and Dr. Cora Beckers in the area of thrombosis and coagulation. Upon completing her degree she was awarded the Silver Prize for the second highest degree grade in the faculty. After completing her undergraduate degree in 2016 she embarked on a PhD at the University of Leeds in Cancer Biology in Professor John Ladburys research group. Particularly focusing on early signaling events in breast cancer, exploring interactions and cellular outcomes of complex formation at receptors when growth factor deprived. This is set to be complete by November 2020.

Abstract:

Introduction: In the absence of ligand stimulation, we have shown that a second tier of signalling is initiated by interactions between the SH3 domains of intracellular kinases and the proline rich motifs of receptor tyrosine kinases (RTKs). When this signalling is perturbed it can lead to pathological outcomes. This secondary tier of signalling has been shown to contribute to poorer outcomes with FGFR2 in ovarian cancer but it has not been widely explored for other RTKs or other types of cancers. One RTK of interest is VEGFR2, which is overexpressed in many cancer types including breast cancer (BC). VEGFR2 is a RTK that regulates angiogenesis, proliferation, survival and migration in response to the ligand VEGF-A. Inside a tumour mass, RTKs on the surface of cancer cells will have limited access to extracellular stimuli, including VEGF-A. Here, someof the response of VEGFR2 may be through these nonclassical interactions with non-activated RTKs and could possibly be used to aid in cancer progression and survival. Objective: To determine whether VEGFR2:SH3- domain-containing protein interactions occur under serum starved conditions in breast cancer, and to assess their impact on cancer cell behaviour. Methods: VEGFR2 expression levels were investigated in BC cell lines (SKBR3 and MCF7 cells) and HEK 293T cells as a control non-cancerous cell line under serum starved conditions for 24 hours. Protein-protein interactions (PPIs) were determined by endogenous Co-IP and via pull down of VEGFR2 constructs containing mutated SH3-binding sites in HEK 293T cells (low expression of endogenous VEGFR2), SKBR3 and MCF7 (high expression of endogenous VEGFR2) cells grown under serum starved conditions and visualised by immunoblotting. Protein expression and purification of the C-terminal tail of VEGFR2, containing only the c-terminal proline rich motif, was used in a pull down in cancer cell lysates and PPIs visualised by immunoblotting.