Day 3 :
- Cancer Basic and Applied Research
Organ-Specific, Cancer Genetics
Anti-cancer drug delivery
Location: Melia Meeting 1&2
Akinori Takaoka, Hokkaido University, Japan
Griffith University, Australia
Title: Cross-talk between two antioxidants, thioredoxin reductase 1 and heme oxygenase-1 and therapeutic implications in multiple myeloma
Time : 10:00-10:25
Prahlad V Raninga has completed M Res at University of East Anglia, England, and currently pursuing PhD at Griffi th University, Australia. His main research interests include cancer biology, cell signaling and molecular cancer therapeutics. His current research is focused onto investigate the therapeutic potential of the antioxidant molecules to treat myeloma. He has published two fi rst author papers in the reputed oncology journals during his early PhD candidature.
Multiple myeloma (MM) is characterized by an accumulation of abnormal clonal plasma cells in the bone marrow. Despite recent advancements in anti-myeloma therapies, MM remains an incurable disease with only a slight increase in the median survival rate to 5 years. Th erefore, more eff ective therapies are needed. Antioxidant molecules are up-regulated in many human cancers, correlating with tumor proliferation, survival and drug-resistance and therefore, have been suggested as potential therapeutic targets. Th is study investigated the cross-talk between two major antioxidant molecules, thioredoxin reductase 1 (TrxR1) and hemeoxygenase-1 (HO-1) and their therapeutic implications in MM. We found that TrxR1 levels are up-regulated in MM cells compared to normal cells. We therefore tested the eff ect of TrxR1 inhibition using a specifi c inhibitor, auranofi n, on MM cell growth. Although auranofi n signifi cantly inhibited TrxR1 activity at the lower concentrations, MM cell proliferation was only inhibited at the higher concentrations of auranofi n. Inhibition of TrxR1 activity up-regulated another oxidative stress-responsive protein HO- 1, which has been shown to act as a secondary anti-apoptotic protein. Inhibition of TrxR1 in conjunction with HO-1 signifi cantly inhibited MM cell growth and induced apoptosis. Th us, HO-1 acts as a secondary anti-apoptotic mechanism in MM. Results showed that TrxR1 regulates HO-1 via the Nrf2 signaling pathway. Th ese fi ndings indicate that TrxR1 alone or in conjunction with HO-1 may serve as an eff ective therapeutic target to treat MM. Hence, this research highlights how understanding the cross-talk between these antioxidant systems may help in designing more eff ective therapeutic strategies to cure MM.
Anglia Ruskin University, UK
Okezie Ofor is a highly experienced physician initially specialized in cardiac and diabetic medicine and is currently pursuing a career in academic medical oncology. He has just completed his PhD in Cell and Molecular Biology from Anglia Ruskin University, Cambridge and Chelmsford, United Kingdom and is considering his options for Postdoctoral studies.
Introduction: CTCF is an evolutionally conserved 11-zinc fi nger protein factor involved in an extensive array of cellular activities whose de-regulation could lead to cellular transformation via interactions with ER-α binding regions and ER-regulated genes, CTCF was shown to compartmentalize the cellular genome into domains. Furthermore it was found co-localized to ER-α in MCF7 cells and had interactions with ER-α during histone deacetylase recruitment and fork-head activity. It is not clear what the regulatory relationship between CTCF and ER-α could be. Aim: To determine whether CTCF expression regulated ER-α expression in the ER+ MCF7 breast cancer cell line. Methods: MCF7 breast cancer cells were transfected with either CTCF expression vectors or si-RNA against CTCF. Following CTCF over-expression and knock-down, changes in endogenous expression of ER-α gene and protein expression were monitored by quantitative polymerase chain reaction (QPCR) and western blot analysis respectively. Results: CTCF plasmid over-expression and si-RNA knockdown was associated with cell rounding but with 96.4% and 95.7% cell viability respectively. Increase in CTCF mRNA on over-expression was associated with a rise in CTCF protein expression. Si-RNA knockdown of CTCF mRNA was accompanied by a corresponding decrease in CTCF protein expression. CTCF over-expression and knockdown appeared to inhibit the ability to detect ER-α protein expression by western blotting. Neither the over-expression nor knockdown of CTCF altered ER-α mRNA expression as detected by QPCR. Conclusion: Alterations in CTCF mRNA expression did not aff ect ER-α gene expression in MCF7 breast cancer cell line suggesting that CTCF may not directly regulate ER-α mRNA expression.
Western University, Canada
Dr. Shawn Li is Professor of Biochemistry at Western University and Canada Research Chair in Functional Genomics and Cellular Proteomics. The Li lab employs an integral approach that combines proteomic tools such as mass spectrometry and peptide and protein arrays with molecular and cellular methods to identify protein posttranslational modifi cations (PTM) and to characterize their roles in cell proliferation, differentiation, migration, apoptosis and the DNA damage response.
Methylation of Lys and Arg residues has emerged as a prevalent post-translational modifi cation (PTM) occurring on numerous non-histone proteins, drastically extending its role beyond the known histone code. We have developed an approach that combines mass spectrometry with peptide arrays and bioinformatics to systematically identify protein methylation and quantify dynamic changes in the methylome associated with tumorigenesis or drug resistance. Our studies not only led to the identifi cation of numerous novel methylation sites, but also generated new insights into how protein methylation regulates cellular functions such as DNA damage repair, apoptosis and drug resistance. With recent advances in mass spectrometry, the stage is now set to decode the methyl proteome and to elucidate, systematically, the mechanisms of interplay between histone and non-histone methylation and between methylation and other types of PTM for cancer diagnosis and intervention.
University of Alexandria, Egypt
Mahmoud Sakr, MD, PhD, FACS, graduated in 1981 and completed his Master and Doctorate Degree (PhD) in Surgery at the Faculty of Medicine, Alexandria University, Egypt. He had his fellowship in Surgery and Organ Transplantation at the University of Pittsburgh School of Medicine, Pennsylvania, USA. He is a fellow of the International college of Surgeons (ICS) and American college of Surgeons (ACS) and is currently the chief, Department of Head & Neck and Endocrine Surgery, Faculty of Medicine, Alexandria University. He published 19 books and 93 articles in esteemed journals, and has been serving as an editorial board member of repute.
Objective: Th e aim of the present study was to determine the incidence of level I cervical lymph node (LN) involvement in patients with metastatic papillary thyroid carcinoma (PTC) and the possible indications of its dissection. Study Design: A prospective clinical study (case series) of 30 consecutive patients with N1b stage PTC, admitted to Alexandria Main University Hospital, and subjected to total thyroidectomy (TT) and neck dissection of all cervical LN levels.. Methods: In addition to demographics and clinical assessment, pre-operative thyroid function tests, cervical ultrasonography and computed tomography scan, and fi ne needle aspiration cytology were performed for all patients, and the fi nal histopathological examination was reviewed. Results: A total of 24 unilateral and 6 bilateral neck dissections were performed making a total of 36 neck dissections. Level I LNs was excised in all patients and proved positive for malignancy in fi ve (13.9%). Levels II, III, IV, V, VI and VII were positive in 52.8%, 58.3%, 58.3%, 33.3%, 63.9% and 22.2%, respectively. Level I involvement correlated signifi cantly with the number of LN levels aff ected (3 or more) (p=0.003) and extensive neck dissection (p=0.04). It was not related to any other single LN level involvement, gender, age, duration of symptoms, family of thyroid cancer, size of largest thyroid nodule, size of largest LN involved, or histopathological variant of the tumor. Conclusions: Th ough not uncommon in patient with PTC, level I cervical LN metastases are associated with multiple level involvement (3 or more) and invasion of the internal jugular vein, spinal accessory nerve or sternocleidomastoid muscle. A careful selection of patients requiring level I dissection is recommended to avoid an unjustifi ed added morbidity of the procedure. Key Words: Th yroid, papillary carcinoma, level I, lymph node, metastases, neck dissection
King Saud bin Abdulaziz University for Health Sciences, Riyadh
Background: Stem cells originating from neonatal cord blood are used worldwide in transplant medicine to treat various diseases. Stem cells effi cacy in the Umbilical Cord Blood (UCB) can be predicted by the number of total nucleated cells (TNC). To optimize the clinical use of stem cell in our population, this study addresses several variables aff ecting TNC count. Methods: Th is is an observational cross-sectional study conducted at King Abdulaziz Medical City in Riyadh, Saudi Arabia. From 2012-2014, 957 UCB units were collected from consented mothers by trained personnel using standard procedure. Data analysis of clinically accepted CBUs was correlated with maternal and infant factors. Results: Based on the TNC accepted level of banking which is at least 90x107 cells, 188 CBUs (19.64 %) were rejected from a total of 957 units. Of the 17 maternal and neonatal variables evaluated, three factors demonstrated a statistically signifi cant predictive value of accepted TNC level: Cord blood volume was the best predictive factor (p-value<0.0001), newborn birth weight (p-value=0.025) and vaginal delivery (p-value= 0.002) Conclusion: Several maternal, neonatal and obstetric factors appear to play a major role in predicating accepted TNC count which can be used to improve the criteria of the donation of stem cells in cord blood unit.