Scientific Program

Day 1

KEYNOTE SPEAKERS
  • Perioperative use of NSAID might prevent early relapses in breast and other cancers: An upstream approach

    Harvard University
    USA
    Biography

    Michael Retsky (PhD in Physics from University of Chicago) made a career change to cancer research thirty years ago. He was on Judah Folkman’s staff at Harvard Medical School for 12 years. Diagnosed with stage IIIc colon cancer in 1994, he opted for a low dose long term chemotherapy protocol that is now called metronomic chemotherapy. Retsky is Editor and Romano Demicheli is Co-Editor of a Springer/Nature book on breast cancer published in July 2017. Retsky is a founder of the Colon Cancer Alliance and has published more than 90 papers in physics and cancer.

    Abstract

    A bimodal pattern of hazard of relapse among early stage breast cancer patients has been identified in multiple databases from US, Europe and Asia. We are studying these data to determine if this can lead to new ideas on how to prevent relapse in breast cancer. Using computer simulation and access to a very high quality database from Milan for patients treated with mastectomy only, we proposed that relapses within 3 years of surgery are stimulated somehow by the surgical procedure. Most relapses in breast cancer are in this early category. Retrospective data from a Brussels anesthesiology group suggests a plausible mechanism. Use of ketorolac, a common NSAID analgesic used in surgery was associated with far superior disease-free survival in the first 5 years after surgery. The expected prominent early relapse events in months 9-18 are reduced 5-fold. Transient systemic inflammation accompanying surgery (identified by IL-6 in serum) could facilitate angiogenesis of dormant micrometastases, proliferation of dormant single cells, and seeding of circulating cancer stem cells (perhaps in part released from bone marrow) resulting in early relapse and could have been effectively blocked by the perioperative anti-inflammatory agent. If this observation holds up to further scrutiny, it could mean that the simple use of this safe, inexpensive and effective anti-inflammatory agent at surgery might eliminate early relapses. We suggest this would be most effective for triple negative breast cancer and be especially valuable in low and middle income countries. Similar bimodal patterns have been identified in other cancers suggesting a general effect.

  • The future place of protons in radiotherapy

    Proton Partners International Limited
    United Kingdom
    Biography

    Karol Sikora is Chief Medical Officer of Proton Partners International. He was the founder of Cancer Partners UK which has created UK’s largest independent UK cancer network with private equity. He was Professor and Chairman of the Department of Cancer Medicine at Imperial College School of Medicine and is still honorary Consultant Oncologist at Hammersmith Hospital, London. He is Dean and Professor of Medicine at Britain’s first independent Medical School at the University of Buckingham and a Fellow of Corpus Christi College, Cambridge. He has published over 300 papers and written or edited 20 books including Treatment of Cancer - the standard British postgraduate textbook, now in its sixth edition. His new book for patients The street-wise patient’s guide to cancer survival has just been published.

    Abstract

    Meaningful large scale randomized trials with protons versus photons are unlikely. Instead the pre-treatment comparison of PBT versus IMRT in individual patients using pre-set metrics of plan quality will be necessary for funding. This assessment would be made objectively by treatment planning software systems. Payers, both government and insurers, will use these criteria to assess the value of PBT in an individual using a comparative equation incorporating tumor control, late toxicity and overall lifetime costs of care. Such analyses will determine the level of the therapeutic plateau in the relationship of cost to clinical outcome gain. The range of published estimates varies enormously from 1.5% (UK, NHS) to 20% in the US. The majority of European strategic plans are assuming a 10-15% utilization of protons in patients treated with radical radiotherapy.

  • An empirical assay for assessing genomic sensitivity and for improving cancer diagnostics

    University of Bradford
    England
    Biography

    Diana Anderson holds the established Chair in Biomedical Sciences at the University of Bradford. She obtained her first degree in the University of Wales and second degrees in the Faculty of Medicine, University of Manchester. She has 450+ peer-reviewed papers, 9 books, has successfully supervised 29 PhDs, and been a Member of Editorial Boards of 10 international journals. She has been or is Editor in Chief of a book Series on toxicology for J. Wiley and sons and the Royal Society of Chemistry respectively. She gives key note addresses at various international meetings. She is a consultant for many international organizations, such as the WHO, NATO, TWAS, UNIDO and the OECD.

    Abstract

    Detection tests have been developed for many cancers, but there is no single test to identify cancer in general. We have developed such an assay. In this modified patented comet assay, we investigated peripheral lymphocytes of 208 individuals: 20 melanoma, 34 colon cancer, 4 lung cancer patients 18 suspect melanoma, 28 polyposis, 10 COPD patients and 94 healthy volunteers. The natural logarithm of the olive tail moment was plotted for exposure to UVA through different agar depths for each of the above groups and analyzed using a repeated measures regression model. Response patterns for cancer patients formed a plateau after treating with UVA where intensity varied with different agar depths. In comparison, response patterns for healthy individuals returned towards control values and for pre/suspected cancers were intermediate with less of a plateau. All cancers tested exhibited comparable responses. Analyses of receiver operating characteristic curves, of mean log olive tail moments, for all cancers plus pre/suspected-cancer versus controls gave a value for the area under the curve of 0.87; for cancer versus pre/suspected-cancer plus controls the value was 0.89 and for cancer alone versus controls alone (excluding pre/suspected-cancer), the value was 0.93. By varying the threshold for test positivity, its sensitivity or specificity can approach 100% whilst maintaining acceptable complementary measures. Evidence presented indicates that this modified assay shows promise as both a stand-alone test and as a possible adjunct to other investigative procedures, as part of detection programmes for a range of cancers.

  • Cancer stem cells in oral tongue, lip and buccal mucosal squamous cell carcinoma express components of the renin-angiotensin system

    Gillies McIndoe Research Institute
    New Zealand
    Biography

    Swee T Tan is the Director of the Gillies McIndoe Research Institute in Wellington, New Zealand. He completed his Medical Training at Melbourne University in 1985, Plastic Surgery Training in New Zealand in 1992, and gained a PhD from Otago University in 2001. In 1995, he was appointed as Consultant Plastic & Cranio-Maxillofacial Surgeon at the Wellington Regional Plastic, Maxillofacial & Burns Unit at Hutt Hospital, where he was the Director of Plastic Surgery from 2000 to 2006 and Director of Surgery 2007-2013. He was appointed as Professor in Plastic Surgery at Otago University in 2008. He is the Founder and Director of the Centre for the Study & Treatment of Vascular Birthmarks, a national referral centre. He has received numerous honours and awards and is well known internationally for his research into the stem cell basis of diseases including vascular anomalies and cancer. He is the author of more than 140 publications and has delivered over 350 lectures at conferences.

    Abstract

    Squamous cell carcinoma (SCC) makes up more than 90% of cancer affecting the oral cavity including the oral tongue, buccal mucosa, floor of mouth, retromolar trigone, hard palate, alveolus and the lip. Treatment of oral cavity SCC (OCSCC) typically involves surgical resection, often followed by radiotherapy, and sometimes biologic agents. Despite this radical treatment, the 5-year survival rate for SCC affecting most oral cavity subsites has remained at 50% for the past 4 decades. Cancer stem cells (CSCs) have been identified in many types of cancers including OCSCC. Our recent data demonstrates the presence of 3 different putative CSC subpopulations within SCC of the oral tongue, buccal mucosa and lip. We have also demonstrated these CSC subpopulations express components of the renin-angiotensin system (RAS). We ahve also shown that the CSCs in one of these cancers studied (oral tongue SCC) also express the protease cathepsins B, D and G (CathG), suggesting the existence of potential bypass loops for the RAS. Our work suggests CSCs as a novel therapeutic target by modulation of the RAS using existing medications.

  • The pathogenesis of spontaneous intracranial hemorrhage in patients with haematological malignancy

    Central Manchester Foundation Trust Manchester
    United Kingdom
    Biography

    John Batchelor is currently Consultant in Emergency Medicine at Central Manchester Foundation Trust, England UK. He is also Honorary Lecturer at Manchester Metropolitan University. He is graduated from Leeds University England in 1982. He is a Fellow of the Royal College of Surgeons of Ireland and Fellow of the Faculty of Emergency Medicine of England. He undertook his MD thesis at University College London. He has written extensively on the subject of minor head injuries. He has presented a paper in Paris in 2012 on a meta-analysis looking at the relationship between cerebral micro bleeds and antiplatelet agents. He has also recently published a meta-analysis on the effect on mortality of platelet transfusions in adults with spontaneous or traumatic antiplatelet associated intracranial hemorrhage. His current research interest lies in the area of risk factors for intracranial hemorrhage in both adults and paediatrics secondary to coagulopathy and thrombocytopenia.

    Abstract

    Spontaneous intracranial hemorrhage is a well-recognized complication in patients with haematological disease. Intracranial hemorrhage is the second leading cause of death in patients with acute myeloid leukemia. The reported mortality is over 50% for patients with haematological malignancy and spontaneous intracranial hemorrhage. The reported incidence of spontaneous intracranial hemorrhage appears to be slightly higher in acute myeloid leukemia (AML) and chronic myeloid leukemia in blast crisis than in other forms of homological malignancy. The distribution of ICH is as follows: Intraparenchymal hemorrhage accounts for about 60% of the reported case series. The remaining sites are distributed between the cerebellum, brainstem, and basal ganglia, subarachnoid, subdural, interventricular and epidural regions. Over 50% of patients will be having more than one intracranial bleeding site on CT. Previously proposed risk factors for spontaneous intracranial bleeding includes: Direct invasion by tumor cells, invasive intracranial sepsis, hyper leukocytosis, and coagulopathy. Abnormalities of clotting include DIC, thrombocytopenia and prolonged prothrombin time. Coagulopathy and thrombocytopenia are probably not the main factors responsible for spontaneous intracranial hemorrhage in view of the fact that neither platelets nor clotting factors are responsible for maintaining cerebral vessel integrity under normal physiological conditions. Cohort studies from patients with idiopathic thrombocytopenia have shown a poor correlation between platelet count and the risk of spontaneous intracranial hemorrhage in both adults and children. Batchelor (2015) has shown that coagulopathy in patients with traumatic intracranial bleeding increases the risk of progressive hematoma progression by an odds ratio of 6.176 (95% CI: 4.727–8.069). This paper will explore other factors which may account for spontaneous ICH in patients with haematological malignancy. This paper will also explore the threshold for platelet transfusions in patients with haematological malignancy and thrombocytopenia based upon the current evidence.

Cancer Treatment and Therapeutics | Onco-Cardiology | Blood Cancer
Chair
Speaker
  • Cardio-oncology- What it is and why we need it?
    Speaker
    Arjun Ghosh
    St. Bartholomew’s Hospital
    United Kingdom
    Biography

    Arjun Ghosh, MBBS, MRCP (UK), MRCP (Card), MSc, PhD, FHEA, is working as a Consultant Cardiologist at Barts Heart Centre (BHC), St. Bartholomew’s Hospital, London and at University College London Hospital (UCLH) is one of the first Cardiologists in the UK appointed specifically in Cardio-Oncology. He helped establish Cardio-Oncology services at both these hospitals. The services deal with screening for cardiotoxicity, monitoring patients on potentially cardiotoxic therapy and managing cardiac complications of cancer therapy. Patients are seen in clinics at BHC twice a week and once a week at UCLH. These clinics are one-stop with investigations (echocardiography, cardiac MRI etc.) on the day enabling rapid assessment and formation of a management plan on the day itself. Alongside the clinical service, Cardio-Oncology research is undertaken at both sites and there is a thriving educational component to the service with fellows from the UK and across the world. He has also established one of the first Cardio-Oncology MDTs in the world at BHC. He will explain the role of Cardio-Oncology in the management of cancer patients and expand on the Cardio-Oncology service models at BHC and UCLH.

    Abstract

    Cardio-Oncology is an emerging specialty. It deals with the cardiac care of cancer patients in the most holistic sense. Screening, monitoring and intervention are the 3 key therapeutic initiatives in cancer patients exposed to potentially cardiotoxic chemotherapy and/or radiotherapy. Cardiotoxicity is a significant burden in those treated with anthracyclines and Trastuzumab and can complicate therapy with newer agents such as proteasome inhibitors. In addition, chemotherapy can result in arrhythmias, myocarditis, arterial and venous thromboembolism and hypertension while radiotherapy can lead to valve disease, pericarditis and diastolic and systolic dysfunction.

  • A new approach strategy to cure cancer
    Speaker
    Adnan Yousif Rojeab
    The London College UCK
    United Kingdom
    Biography

    Biography

    Abstract

    The original of the cancer is a special mechanism which been created to eliminate the severe damage against the body, while the immune system is failing to cure the damages. The right method to vanish the action of the cancer is by applying a direct, right and simple treatment to those of previous diseases, which have caused to create the cancer, but without trying to treat the cancer itself. There is a similarity in lengthening characteristic of the telomere, in every replication of DNA, between the cancer cells and with those of stem and germ cells, where these cells are not forming a tissue. While in somatic cells, the telomere shortens in every DNA replication, which is by the action of remnant magnetisation. One other, possible, method to eliminate the cancer is, by, exposing the cancer cells to a suitable amount and direction of a magnetic field. This method is aimed in direction of inhibiting the lengthening of telomere, towards the characteristic of somatic cells.

  • Hypericum triquetrifolium Turra against cyclophosphamide-induced hemorrhagic cystitis in rats
    Speaker
    Songul Cetik
    Mardin Artuklu University
    Turkey
    Biography

    Songul Cetik is an Assistant Professor at Vocational Higher of Health Services, Mardin Artuklu University in Turkey. She has completed her graduation from Eskisehir Osmangazi University, Faculty of Arts and Sciences, Department of Biology, 2009. She has done her Post-graduation from Eskisehir Osmangazi University, Faculty of Science, 2014.

    Abstract

    A cyclophosphamide (CYP) usage is limited by side effects of it, are commonly used as antineoplastic drug. Hemorrhagic cystitis is one of the most important side effects of CYP chemotherapy. Antioxidants such as Hypericum triquetrifolium Turra (HT) show an important antioxidant and anti-carcinogenic properties with its rich contents. This study investigated the possible cytoprotection effect of HT (25, 50, 100 mg/kg, i.p., for 6 days) in CYP (150 mg/kg, single dose, i.p.) treated rats, and attempted to obtain a suitable new agents. Creatinin (CK), malondialdehyde (MDA), total oxidant capacity (TOC), total antioxidant capacity (TAC) and oxidative stress index (OSI) levels were measured in blood serum. Furthermore, the bladder tissue samples were investigated histopathological. In the only CYP group CK, MDA, TOC and OSI levels found increased while TAC level decreased. According our results high dose CYP caused the edema, necrosis, bleeding and tissue erosions, hemorrhage and separation of the muscle fibers supported the our biochemical results. After pretreatment with HT doses observed an important decrease in the CYP toxicity, decreased the cell damage and oxidative stress parameters while increased TAC. Based on the present experimental study’s findings, we may say that HT pretreatment has the potential to be a therapeutic option for the management of CYP-induced HC.

  • Childhood leukemias in Khyber Pakhtoonkhwa and Afghanistan children, visiting Hayat Abad Medical Complex Hospital
    Speaker
    Shahtaj khan
    Hayatabad Medical Complex
    Pakistan
    Biography

    Biography

    Abstract

    Objective: The aim of the present study is to evaluate the frequency of childhood leukemias in the children from different districts of Khyber Pakhtoonkhwa (KP) and Afghanistan presenting to Hayat Abad Medical Complex Hospital, Peshawar. Material & Method: This descriptive cross sectional study was conducted in Pathology department Hayat Abad Medical Complex hospital, Peshawar. Duration of the present study was, from January 2014 to December 2016. A total number of 605 children were enrolled up to 18 years of age, who suspected to have leukemia went through bone marrow examination by different department clinicians. 3 ml blood was collected in EDTA tube (purple top) and complete blood count was performed by hematology analyzer. By aseptic techniques bone marrow aspiration and bone marrow trephine biopsy samples were collected from all patients. Slides were papered from bone marrow aspirates, fixed with methanol and stained with Giemsa, myeloperoxidase and periodic acid Schiff stain. Trephine biopsy slides were stained with haematoxylin and eosin and reticuline stain. Immunohistochemistry was done after initially seeing of bone marrow aspirate slides. All data was documented and statistical analysis was performed by SPSS-20 software. Results: Among 605 children, 173(61.6%) were males and 108(38.4) were females and their age range from 3 months to 18 years with median age of 9.8 years. In total children 281 (46.5%) were diagnosed different type of leukemias. Out of 281 cases, 208(74.03%) were diagnosed to have acute lymphoblastic leukemia and rest of the children were 61 (21.70%) acute myeloid leukemia, 7 (2.49%) chronic myeloid leukemia, 3 (1.07%) had juvenile chronic myelomonocytic leukemia (JCMML). Conclusion: In the present study acute lymphoblastic leukemia were more prevalent leukemia in the children of Khyber Pakhtoonkhwa and Afghanistan. Juvenile chronic myelomonocytic leukemia was found less commonest leukemia in the present study.

  • Stem cell transplantation: A new treatment for blood cancer patients
    Speaker
    Naser Mobarra
    Golestan University of Medical Sciences
    Iraq
    Biography

    Naser Mobarra has received his PhD (2014) from Tehran University of Medical Sciences, Tehran. He has published more than 25 papers in reputed journals and has been serving as an Editorial Board Member of few ISI journals.

    Abstract

    Cancer is the major cause of death in the world today. The International Agency for Research of Cancer estimated that 94.4 thousand deaths would occur in 2012 due to blood cancer in the countries of the European Union. All cancers demand new treatments, and we focused on specific type of cancer: blood cancers or haematological malignancies. There are four broad categories of blood cancers: leukaemia, myeloma, Hodgkin lymphoma and non-Hodgkin lymphoma. Together, these account for around 9% of all cancers and are currently the fourth most common in both males and females in the world. Because of this high mortality rate, the development and progressive evolution of stem cell transplantation in recent decades has been an important medical advance. Haematopoietic stem cell transplantation (HSCT) has become an effective treatment for malignant and benign haematological diseases that could not be cured by other therapies, allowing for an increasing number of patients to become long-term survivors. It is an essential part of the therapeutic strategy which is clinically recommended for blood cancer patients whose clinical condition indicates transplantation. Hematopoietic stem cells (HSCs) are found at the apex of this system and are defined by their ability to self-renew and to give rise to all hematopoietic lineages. HSCs can be identified through the expression of CD34 on their surface and a lack of expression of CD38.

Young Research Forum
Chair
Speaker
  • Evaluation of the effects of platelet rich plasma in regeneration of the spinal cord
    Speaker
    Muhammad Uzair Rehman
    Jinnah Medical and Dental College
    Pakistan
    Biography

    Muhammad Uzair Rehman has received his Bachelor of Medicine and Bachelor of Surgery from Liaquat National Hospital and Medical College Karachi, Pakistan. He is currently an MPhil Scholar at Dadabhoy Institute of Higher Education. During 2013-2014, he completed his House job at Abbasi Shaheed Hospital and Jinnah Post-graduate Medical Centre following which in November 2014 he joined Musavvir Stem Cell Clinic in the capacity of Research Associate. In January 2015, he took up the position of Lecturer at Jinnah Medical and Dental College finally parting ways in 2017 and taking up the post of Senior Lecturer at United Medical and Dental College. He is currently pursuing his MPhil in the field of Molecular Medicine and Medicinal Chemistry. His current research interests include Stem Cells, Platelet Rich Plasma, Platelet Rich Fibrin, Regenerative Medicine and Virology.

    Abstract

    The purpose of study is to explore the efficacy and safety of platelet rich plasma (PRP) and adipose-derived stem cells in the non-operative management of shoulder tendinopathy amongst individuals with spinal cord injury. In this case in road traffic accidents that cause spinal injuries to the central nervous system, which increased morbidity and motility. The complications in patients were developed, resulting to a challenging problem for medicine. Platelet is the important component of blood which naturally holds the growth factors and cytokines. As a concentrated source of autologous platelets, PRP contains several different growth factors and other cytokines stimulating and healing of soft tissue. Platelet rich plasma therapy utilizes growth factors present in alpha granules of platelets in autologous adult stem cells reside in adult tissues and serve as the source for their specialized cells. In response to specific factors and signals, adult stem cells can differentiate and give rise to functional tissue specialized cells. In recent advancement in the field of regenerative medicine it was thought that this would grant a new approach to this problem, as it had proven beneficial in the repair of peripheral nerve injuries and their regeneration. This study was done to evaluate the effect of Platelet Rich Plasma (PRP) and adult stem cells (ASC) and its effect on the spinal cord post trauma. Subsequently, it was seen that PRP and ASC proved beneficial with marked positive effects in both muscle tone and muscle control and marked clinical improvement although it can still be said that further research must be done in this field.

  • Role of platelet rich plasma in repairing of non healing wounds and bones in clinical setup
    Speaker
    Maria Fatima Ali
    Jinnah Medical and Dental College
    Pakistan
    Biography

    Maria Fatima Ali received her Bachelor of Dental Surgery from Jinnah Medical and Dental College Karachi Pakistan. She is currently an MPhil scholar at Dadabhoy Institute of Higher Education. In 2014, she joined Hamdard University Dental Hospital where she did her House job following which in 2015 she joined the Department of Pharmacology as a Lecturer and later that year she took up the position of Research Associate at Musavvir Stem Cell Clinic. She is currently pursuing her MPhil degree in the field of Molecular Medicine and Medicinal Chemistry. Her current research interests include Stem Cells, Platelet Rich Plasma, Platelet Rich Fibrin and Regenerative Medicine.

    Abstract

    PRP stands for Platelet Rich Plasma, which is a main component of a PRP stem cell injection. In the last few decades, thousands of patients have benefited from platelet rich plasma (PRP) therapies, emerging as a safe alternative in many different medical fields. The term is used very loosely to include anything that has growth factors and cytokines derived from blood (Platelets). When cells talk to each other, they make proteins and peptides that are the messages that pass from one cell to another and determine how the cell will respond. These are called cytokines and include growth factors. PRP stem cell injections for the knee, hip and spine use these cytokines to control the actions of surrounding cells. Platelets store granules of these cytokines that can be harvested and used. The use of platelet-rich plasma (PRP) in medicine has become increasingly more widespread during the last decade. Most studies on the subject are carried out in areas such as orthopedics, sports medicine, and odontology. Recently platelet-rich plasma (PRP) has also been used in the dermatologic and wound healing field, where PRP has been used in order to promote accelerated wound healing and as an adjuvant treatment in rejuvenation, alopecia, hair loss and even following laser sessions. The use of platelets was particularly fortuitous given that the main initial interest was to take advantage of the adhesive and haemostatic properties of the homologous fibrin during bone surgery. A realization of the clinical potential of PRP-therapies has also followed the positive clinical observations, such as enhanced bone formation and anti-inflammatory functions, during oral and maxillofacial applications. PRP seems to have a role to play in the treatment of extra-articular symptoms.

  • Stem cell donation decision in Saudi Arabia: Factors and attitudes
    Speaker
    Maria Mufti
    Princess Nourah bint Abdulrahman University
    Saudi Arabia
    Biography

    Maria Mufti is a third year Medical student at Princess Nourah Bint Abdulrahman University. She graduated from Al-Rowad High School in 2012 with percentage of 98 and finished four years in Medical College. She had her first Medical Research about stem cells and stem cells donation: factors and attitudes in 2016\2017. She had courses such as: English course at Alfaisal Universal Academy with a grade of 90 at the 6th level; other is self-development and problem solving and much other Medicine related courses. Her good attendance at English classes made her eligible to take the IELTS exam with grade of 5.5. She is interested in volunteering community services regularly, as she volunteered once to be a photographer for orphan children, she volunteered also in recovering from cancer day as a speaker about cancer awareness, also she was four times a volunteer at campaigns of stem cell donation center at King Faisal Hospital taking swabs and register donors.

    Abstract

    Background: Stem cells (SC) transplantation becomes the base line management in many diseases. The SC donors’ number is still insufficient to cover the SC transplants’ needed number. Encouraging adults to be SC donors is the main donation concern. Objective: The objective of the study is to identify the factors affecting Saudi population’s attitudes concerning SC donation. Materials & Method(s): This is a case control study with a 600 questionnaires filled by Saudi participants aged between 18-50 years in SC donation campaign, King Faisal Hospital, Riyadh. Result(s): 300 males and 300 females with mean age of 29.24 ±9.32 years were included. Although 41.7% of participants were aware about SC, 93% of them had bad knowledge score. 67.3% were registered in SC donation campaign as a donor while 15.5% of participants had knowledge about Saudi SC donation centers. A significant difference was found between registered and non-registered participants regarding many factors e.g. age, education level and knowledge score (P value?0.05). The main encouraging positive attitude was relieving patient’s pain (65.3%) while the main negative one was considering SC donation as unsafe procedure (35%). Conclusion(s): The majority of Riyadh’s population accepted the idea of SC donation and registered in stem cell donation campaign; however, there was lack of knowledge about SC and Saudi donation centers. Recommendations: Awareness strategies are urgently needed to enhance population’s SC knowledge, clarify the role of Saudi stem cell donation centers and improve their attitude by correcting wrong ideas.

  • Stem/progenitor cells in human milk and relations between number of cells in human milk and breastfeeding mother-infant dyad
    Speaker
    Dzwigala M E
    Medical University of Warsaw
    Poland
    Biography

    Monica Dzwigala is a 5th year student of Faculty of Medicine at the Warsaw Medical University, Poland. In 2011, she received her Master of Science degree from the Warsaw School of Economics. From 2015, she started taking part in projects carried out by Students' Scientific Group in the Department of Obstetrics and Gynecology under the supervision of Assoc. prof. Ewa Romejko-Wolniewicz (Chief of Department Krzysztof Czajkowski PhD, MD) and she is also involved in basic research working in the Translative Platform for Regenerative Medicine, Medical Research Centre, Polish Academy of Sciences under supervision of Anna Sarnowska PhD, MD (Chief of the Platform of Regenerative Medicine in Polish Academy of Sciences). She is interested in the Stem Cell Biology field, especially human mesenchymal stem cells, human placenta stem cells, human breast stem cells and cervical cancer stem cells. In the area of obstetrics and gynecology, she is involved in the research concerning pregnancy programing, intrauterine infection, amniotic fluid microbiome, pregnancy diabetes and hypertension, perinatology

    Abstract

    Human breast milk consists of different types of cells: leukocytes, epithelial cells, fibroblasts and pericytes. The aim of this study was to confirm presence of stem/progenitor cells in human milk, to evaluate their pluripotent and regenerative potential and to test correlation between mother, infant and number of cells in human milk. Fresh milk samples were acquired from women 0-7 days post-delivery. The consent according to the Ethics Committee of Warsaw Medical University guideline was obtained from each woman. The samples were collected manually or by breast pump from 47 mothers. Cells isolation was performed within 4 hours after sample collection. Various types of media were used in cells culture (MammoCult, DMEM + 10% FBS and others). Cells were characterized by flow cytometry (FC), RT-PCR and immunocytochemistry. Health status of the mother and the child was estimated. Anthropometric data was obtained from patients’ history. Stem/progenitor cells present in human milk displayed heterogeneous expression of pluripotency genes characteristic for human embryonic stem cells such as: transcription factors OCT4, SOX2 and NANOG. No statistical relationship was found between number of cells in human milk and any of the following: previous surgical procedures, marital status, smoking during pregnancy, regular or irregular menstruation cycle, child’s sex and others. Negative correlation (r=-0.5384, p<0.0012) was found between the day of sample collection and the number of milk cells. The study confirms presence of stem/progenitor cells in human breast milk and the correlations might argue the decreasing number of cells in human breast milk during first week from delivery.

  • Capicua regulates self-renewal and tumour progression of breast cancer cells
    Speaker
    Jeehyun Yoe
    Pohang University of Science and Technology
    South Korea
    Biography

    Jeehyun Yoe is a PhD candidate with particular interests in Stem Cell and Cancer Biology. Her current research has 2 aims: 1) to better understand the role of CIC in tumourigenic process in different cellular contexts and environments and 2) to further identify the molecular mechanisms that regulate CSC characteristics. Prior to enrolling at POSTECH for the combined MS and PhD program, she graduated with a BS in Biology and minors in Chemistry and Music from the University of North Carolina at Chapel Hill, USA.

    Abstract

    Cancer stem cells (CSCs) are capable of tumour initiation and growth, and play a critical role in metastasis, therapeutic resistance, and disease recurrence in breast tumours. Therefore, if cancer arises and is maintained by the small population of CSCs within the bulk tumours, it is of central importance that definitive marker genes for CSCs are identified and regulatory mechanisms that promote stem cell maintenance be understood. Here, we show that the developmentally regulated HMG-box protein Capicua (CIC) is a transcriptional repressor that suppresses CSC properties in both the luminal and basal/myoepithelial subtypes of breast cancer cells. Mammosphere formation in culture was used to reveal stem cell properties, where expression of CIC was consistently down regulated in primary mammospheres in comparison to parental adherent cells then in secondary mammospheres upon serial passage. Knockdown of CIC increased mammosphere formation, while CIC overexpression prevented mammosphere formation, effect dependent on continuous CIC expression. Furthermore, CIC knockdown MCF7 and MDA-MB-231 breast cancer cells contained a higher percentage of EpCAM+/CD44+/CD24low/ cancer-initiating cells than in control cells grown as monolayer cultures and propagated as mammospheres. Loss of CIC relieved repression of PEA3 group genes, especially ETV4, which was necessary and sufficient for driving mammosphere formation. Moreover, we observed upregulation of the pluripotency-associated transcriptional factor SOX2 in MCF7 CIC knockdown cells and demonstrated significant rescue effect on mammosphere formation following SOX2 knockdown in CIC knockdown cells. Therefore, we propose CIC as a potential biomarker of breast cancer stem cells and a novel target in stem cell and cancer therapy.

Day 2

KEYNOTE SPEAKERS
  • Tumorspheres from in vitro transformed cell lines show molecular signatures related to stemness and transformation

    Institute of Molecular Genetics
    Italy
    Biography

    Chiara Mondello is Senior Researcher and Group Leader at the Institute of Molecular Genetics of the National Research Council in Pavia (Italy). Her main interests concern the study of genome instability and cellular transformation in mammalian cells. She has published more than 80 papers in peer-reviewed journals and several chapters in books. She has been the Editor of the book “Multiple Pathways in Cancer Development” (Transwell Research Network).

    Abstract

    Evidence indicates that a subset of cells endowed with high tumorigenic potential and stemness features (cancer stem cells: CSCs) is responsible for tumor initiation and maintenance in several cancers. In this study, we used a tumor cellular model developed in our laboratory from telomerase immortalized human fibroblasts (named cen3tel) and the tumorsphere assay to possibly isolate and characterize CSCs from in vitro transformed cells. We found that cen3tel cells were able to form spheres (frequency ~ 2-10%) and sphere cells showed self renewal capacity and Sox2 overexpression, suggesting that in these populations there is a subset of cells with CSC-like features. The characterization of sphere cells revealed that they displayed the activation of pro-survival mechanisms, through the expression modulation of genes as c-MYC, GNL3 and Notch, and the tumor suppressor miR-34a, which could favor the growth of cells in suspension upon detachment from a solid support. Moreover, genome wide gene expression profiles of sphere cells relatively to adherent cells revealed an extensive transcriptional reprogramming involving several stemness and cancer-related genes, indicating that transformed cells are highly plastic entities adopting specific gene expression programs depending on different environmental conditions. However, sphere cells were only slightly more tumorigenic in vivo than adherent cells suggesting that different subpopulations can support tumorigenicity in transformed cells, highlighting a further level of complexity in tumor heterogeneity.

  • Infantile haemangioma : A human model for tissue regeneration

    Gillies McIndoe Research Institute
    New Zealand
    Biography

    Tinte Itinteang serves as the current Chief Scientific Officer and the Evans Family Research Fellow of the Gillies McIndoe Research Institute (GMRI) in Wellington, New Zealand. He completed his Medical Training at the Melbourne University in 2001, and then completed his Basic Medical Residency in New Zealand, from 2008-2010. He completed his PhD from Victoria University of Wellington, NZ on the role of stem cells and the renin-angiotensin system (RAS) in infantile haemangioma. From 2012-2014, he was appointed as a Research Fellow at the Gillies McIndoe Research Institute, during which he spent six weeks at the Friedlander laboratory at The Scripps Research Institute in San Diego investigating the role of iPSCs for disease modelling. He was then appointed as the Chief Scientist of the GMRI from 2015. His work on the role of stem cells and the RAS in infantile haemangioma has been acknowledged with the International Society for the Study of Vascular Anomalies John Mulliken award as well as several national and international honours. He is the author of over 50 peer reviewed articles and has given over 100 presentations at international conferences.

    Abstract

    Infantile haemangioma (IH) is the most common tumour of infancy, characterised by an initial proliferation with aggressive vasculogenesis, followed by spontaneous slow involution leaving a fibro-fatty residuum. IH affects about 10% of infants and has a predilection for female, Caucasian and premature infants. We have demonstrated the presence of embryonic-like stem cells in the endothelium of proliferating IH that express markers associated with mesenchymal and haematopoietic plasticity. These primitive cells are also the putative source of the fibro-fatty tissue that naturally occurs during involution of this tumour. This presentation focuses on the role of the primitive endothelium in the pathoetiogensis of IH and their ability to form downstream definitive mesenchymal and haematopoietic cells. It will also cover our insights into the role of the renin-angiotensin system (RAS) in the regulation of this primitive population, underscoring the novel use of RAS modulators in the treatment of problematic IH. The potential to exploit IH as a human model for directed regenerative medicine will be discussed

  • Are cancer stem cells really healthy cells being reprogrammed back to a naïve stem cell state?

    Minerva Biotechnologies
    USA
    Biography

    Cynthia Bamdad holds a BS in Physics from Northeastern University and a PhD in Biophysics from Harvard University. As a PhD candidate and without the benefit of an advisor, she invented the first electronic DNA chip that she commercialized at a California startup, which was then sold to Motorola for $300M; the chip is now the core of an FDA-approved diagnostic device marketed by Genmark. She is sole or lead inventor on over a hundred patent applications, including for novel technologies that enabled Minerva Biotechnologies’ groundbreaking discoveries in basic cancer biology.

    Abstract

    The intersecting space between stem cells and cancer stem cells is rapidly expanding. Many of the markers, previously thought to be stem cell markers, are now being shown to be markers of metastasis as well. Similarly, metastatic markers such as CXCR4, have now been shown to be markers of the earliest stem cells, called ‘naïve’ stem cells. Here, we report the discovery of a novel stem cell growth factor, NME7-AB, that induces human stem cells to revert to the earliest naïve state. NME7-AB is naturally expressed in every cell of a human Day 3 morula, but by Day 5 is only expressed in the cells of the inner cell mass, which are naïve by definition. Although this new growth factor should be turned off for adult life, we have found it expressed in nearly every metastatic tissue we have examined. In vitro and in vivo, NME7-AB induces cancer cells to become more metastatic; they upregulate metastatic markers and form tumors in mice from as few as 50 cells. Daily injections of NME7-AB into the tumor-bearing mice caused the solid tumor cancers to metastasize. These data are consistent with the idea that cancer cells are being reprogrammed back to a stem cell-like state, wherein the metastatic cancer cells, aka cancer stem cells, are reverted all the way back to the naïve stem cell state. These data suggest that agents that inhibit naïve stem cell pluripotency or growth will also be inhibitors of cancer cells and, more particularly, cancer stem cells.

  • Defining and exploiting the clinical mechanism of activity for alvocidib in acute myeloid leukemia patients

    Tolero Pharmaceuticals
    USA
    Biography

    Steven L Warner specializes in small molecule drug discovery, new screening platforms in drug discovery, and translational research focusing on cancer therapeutics. He is an expert in the discovery of novel cancer agents and has played integral roles in moving multiple compounds into clinical trials. He earned his graduate degree in Pharmaceutical Sciences at the University of Arizona. He completed a postdoctoral fellowship under the mentoring of Dan Von Hoff at the Translational Genomics Research Institute (TGen). He is currently the Vice President of Drug Discovery and Development at Tolero Pharmaceuticals.

    Abstract

    Alvocidib drug development has largely focused on the inhibition of cell cycle regulating CDKs. However, recent clinical activity in leukemia is not fully accounted for by cell cycle inhibition. We set out to more fully understand the mechanism of alvocidib particularly in leukemia patients that were benefiting significantly from the treatment. In addition to the cell cycle regulating CDKs, alvocidib has very potent activity against CDK9 (IC50=1.5 nM). CDK9 is responsible for controlling the transcriptional pause release that is important for the expression of certain genes. One of the most universally regulated transcripts by CDK9 is the anti-apoptotic family member, MCL-1, a member of the BCL-2 family involved suppressing cell death. Alvocidib treatment results in a concentration and time-dependent inhibition of MCL-1 expression in cancer cells. To further validate the CDK9/MCL-1 axis as the therapeutic target of alvocidib in, we utilized an approach called mitochondrial profiling to interrogate the dependencies that leukemia cells have on BCL-2 family members and retrospectively screened archived patient samples from a previously completed phase II clinical trial. We discovered that the patients that had a strong dependency on MCL-1, identified by a high NOXA priming score, where those that showed profound benefits from alvocidib. These findings led us to conduct an on-going phase II prospective biomarker trial where we are prescreening patients for NOXA priming and enrolling patients with a score ?40%. Taken together, these results highly support the conclusion that alvocidib works through a mechanism that targets CDK9 activity and MCL-1 expression.

Cancer stem cell | Molecular Medicines for Cancers| Stem cell markers | Breast Cancer Stem Cells | Cancer Stem Cells in Brain Gliomas
Chair
Speaker
  • Use of 3D spheroid cultures to screen for drugs targeting cancer stem cells
    Speaker
    Ines Prieto
    StemTek Therapeutics
    Spain
    Biography

    Ines Prieto Remon is currently Senior Researcher at StemTek Therapeutics, a biopharmaceutical company located in the Basque Country, Spain. She earned her Bachelor of Biochemistry at the University of the Basque Country, Spain, in 2006, and her PhD in Molecular Biology and Biomedicine from the University of Cantabria, Spain, in 2013, working with Dr Carlos Pipaon Gonzalez and Dr Marian Ros. In her thesis work she studied signaling pathways in Fanconi anemia patients samples, regarding their aberrant acute sensitivity to chemotherapeutic agents. She also studied microphthalmia with Fancd2-/- mouse model. After her PhD, Ines accepted a postdoctoral position at the Laboratory for Experimental Hematology & DNA Repair, at Herman B Wells Center in Indianapolis, IN, US. There, she worked with Dr. Helmut Hanenberg in a project which aimed to study the protective effect of compounds in order to reduce/remove side effects of chemotherapy.

    Abstract

    The cancer stem cell (CSC) concept has important implications not only for our understanding of carcinogenesis, but also for the development of cancer therapeutics. There is a growing body of preclinical evidence showing that cancer stem cells contribute to chemotherapy and radiation resistance in breast cancer. The use of drugs that interfere with stem cell self-renewal represents the strategy of choice for novel effective anti-cancer treatments, but also a great challenge because cancer stem cells and their normal counterparts share many pathways. The biology of cancer stem cells has proven complex and difficult to translate into effective therapeutic strategies. The question arises as: how do we test compounds for anti-cancer stem cell activity? The answer is: phenotypic screening. There are indeed several functional assays well validated in the scientific literature that have been used for years associated to the ability of cancer cells to demonstrate stem cell behavior. The most relevant is the 3D tumor spheroid assay. This assay has been used to uncover and culture stem cells from many tissues as well as from tumors. There are multiple reports now, that show that spheroid derived cells are enriched in tumor initiating or cancer stem cells, derived from cell lines and from natural fresh tumors as well. Here, we describe the use of 3D spheroid models to profile compound activity against cancer stem cells. Furthermore, a case of compounds preventing hypoxia-inducible transcription factor (HIFs) activity is presented. Recently, HIF transcription factor biology has been linked to pathways that regulate stem cell self-renewal and pluripotency, suggesting a new mechanism whereby HIF proteins may drive tumor growth, through the generation of tumour-initiating cells or cancer stem cells. Therefore, targeting the HIF pathway may provide a novel therapeutic avenue to target cancer stem cells. We demonstrate that interfering with HIF pathway activation prevents mammosphere formation, validated through independent confirmation through Sox2 promoter activation, Aldefluor® assay and in vivo proof-of concept experiments targeting tumor initiation.

  • Chemotherapy curable malignancies; Unique genetic events, frozen development, natural apoptosis and absent cancer stem cells
    Speaker
    Philip Savage
    Brighton and Sussex University Hospitals NHS Trust
    United Kingdom
    Biography

    Philip Savage is a Consultant Medical Oncologist in Brighton, UK. His Medical degree is from Bristol University and trained in Medical Oncology at the Royal Marsden and Hammersmith Hospitals in London. He previously specialised in the treatment of trophoblast and germ cell tumours whilst working at Charing Cross Hospital in London. He holds a PhD in tumour immunology from London University and has additional research interests in healthy economics and cancer treatment history.

    Abstract

    Despite over 40 years of the ‘War on Cancer’ the list of metastatic malignancies that can be cured with drugs is unchanged from the 1970s. Whilst the paradigm of cancer cells being sensitive to DNA damaging chemotherapy as a result of rapid growth and then developing chemotherapy resistance and hence avoiding being killed is well established. We would like to present an alternate interpretation of the data and a new hypothesis. The new hypothesis relates to the biological properties of the chemotherapy curable cancers which comprise trophoblast tumours, germ cell tumours, acute leukemia, high grade lymphoma, and the rare childhood malignancies. Each of the chemotherapy curable malignancies arises from specialist cells that naturally undergo DNA manipulations that are intrinsically associated with high levels of endogenous apoptosis during development. Trophoblast tumours arise from the cells of conception, which have just undergone nuclear fusion. Germ cell tumours arise from pre-malignant precursor cells that are subject to pressures to undergo meiosis and mitosis. In the B cell malignancies, acute leukaemia that arises from cells linked to VDJ rearrangement of the immunoglobulin genes, whilst diffuse large B cell lymphoma which is closely linked to somatic hypermutation. Each of these unique genetic processes is naturally linked to a period of extreme sensitivity to DNA damage/apoptosis and we would argue that this apoptotic sensitivity is then maintained in the malignant cells arising at these developmental points. The other key biological characteristic the chemotherapy curable malignancies have is that their unusual developmental pathway means that they are not linked to any conventional hierarchical cancer stem cells. As a result, there is no pool of chemotherapy resistant stem cells available to replenish the tumour after treatment. Further pathway based research may be interesting and lead to novel therapeutic avenues.

  • The expression of the classical stem cell markers in pancreatic adenocarcinoma cell line
    Speaker
    Hussain R Al-Turaifi
    Newcastle University
    United Kingdom
    Biography

    Hussain R Al-Turaifi obtained his PhD from North East England Stem Cell Institute, Faculty of Medical Sciences, Newcastle University UK and is focusing on Translation Medical Research through enrolling in Translational Medicine Program at The University of Edinburgh, College of Medicine and Veterinary Medicine, School of Biomedical Sciences Edinburgh. As Head of Referral Laboratory, Head of Blood Bank Donation Testing Center and Consultant of Molecular Pathology and Clinical Biochemistry he concentrates on diagnostic clinical laboratory at King Fahad Hofuf Hospital, KSA. He worked in academic field as a faculty of Biomedical School, Newcastle University and in the Department of Medical Biochemistry, College of Medicine, Dammam University, KSA

    Abstract

    Pancreatic cancer has been the third leading cause of cancer-related death in USA. Most of the cancer patients get diagnosed in late stage and this minimizes the effectiveness of surgical intervention to less than 20 percentage. Moreover, chemo-radio therapy is not curative thus the survival rate of patients with pancreatic cancer after 5-years was 7%. In USA, 53,070 new cases were estimated diagnosed with pancreatic cancer in 2016, while 41,780 patients was the estimated death from pancreatic cancers. Similar percentage was reported globally, estimated by World Health Organization in 2012 [23]. Presence of cancer stem cells (CSCs) within pancreatic tumor was reported by several groups using unspecific biomarkers. Pluripotent transcription factors such as OCT4, SOX2 and NANOG, that upregulated in embryonic stem cells in contrast to somatic cells, were detected in various types of cancer tumors from adult patients. The aims of this study was to investigate the expression of the classical stem cell markers in pancreatic adenocarcinoma cell line (PANC1). PANC1 cells were characterized by RT-PCR/immuno-staining. Transient over-expression of stem cell promoter-driven reporter plasmid Oct4-eGFP was undertaken using Lipofectamine 2000 transfection reagent. Several embryonic stem cell markers and other cancer related markers were detected which illustrate the nature of pancreatic cancer.

  • The activation of RAF/MEK/ERK kinase cascade by variable ?3-?C loop deletions triggers oncogenesis
    Speaker
    Hu Jiancheng
    National Cancer Centre Singapore
    Singapore
    Biography

    Hu Jiancheng received his PhD from University of Colorado Denver in 2007 and then Post-doctoral training at Washington University in St. Louis and Howard Hughes Medical Institute. Since 2014, he has joined National Cancer Centre Singapore where he has served as the Principal Investigator at the Laboratory of Cancer Signaling. He has published more than 15 papers in international renowned journals. His research interests include: (1) the regulatory mechanism of RAF kinase and other oncogenic protein kinases under normal/pathological conditions; (2) molecular basis that underlie intrinsic and acquired resistance of kinase inhibitors in clinic treatment of cancers; (3) the development of novel kinase inhibitors.

    Abstract

    RAF/MEK/ERK kinase cascade has well-defined role in cancer development. Aberrant activation of this kinase by genetic alterations exists in >40% human cancers, which functions as a driver to trigger cancer pathogenesis. In current study, we identified a new catalogue of mutations in RAF and MEK with variable deletions of ?3-?C loop. These mutants are constitutively active and highly oncogenic in vitro and in vivo. To develop strategies for targeting these mutants-driven cancers, we tested whether they were sensitive to RAF/MEK inhibitors that used for clinic treatment of BRAF (V600E)-harboring cancers or undergoing clinic trials, and found that all of them exhibit a strong drug resistance at cellular level and in tumor-xenograft mouse model. To explore molecular mechanism that underlies this phenomenia, we next carried out a serial of biochemistry and structral analysis and demonstrated that ?3-?C loop deletions stimulate the homo-oligomerization of both RAF and MEK, which not only triggers their kinase activity but also dramatically decreases their drug affinity. Together, our study provides a solid evidence that RAF and MEK mutants with ?3-?C loop deletions function as a cancer driver and a clear molecular basis that ?3-?C loop deletions activate RAF and MEK and lead to strong inhbitor resistance, and appeals a development of new inhibitors.

  • Identification of a novel target that regulates breast cancer stem cells
    Speaker
    Monther Al-Alwan
    King Faisal Specialist Hospital and Research Centre
    Saudi Arabia
    Biography

    Monther Al-Alwan has completed his PhD in immunology from Dalhousie University and postdoctoral studies from University of Manitoba, Canada. He is a Scientist at the stem cell and tissue re-engineering program (SCTRP) at King Faisal Specialist Hospital and Research Centre and Adjunct Associate Professor at AlFaisal University, Riyadh, Saudi Arabia. Currently, he is actively involved in dissecting the molecular pathways that regulate the function of cancer stem cells and how this is related to chemoresistance and metastasis. He has more than 22 peer-reviewed publications in reputed journals and has been serving as an Editorial Board Member of various international journals.

    Abstract

    There have been significant advances in breast cancer treatment, which have been attributed to the use of targeted therapy in combination with surgery and chemotherapy. However, the tumor-related mortality remained high mainly due to chemoresistance resulting in relapse and metastasis. Chemoresistance is widely believed to be regulated by a small subpopulation of the tumor bulk that possess stem cell-like features and thus are called cancer stem cells (CSCs). We have shown significant association between worse clinical outcome in breast cancer patients, including metastasis and shorter survival, and expression of fascin, an actin-bundling protein. Moreover, we have also reported that fascin is a critical mediator of breast CSCs and chemoresistance, via the activation of focal adhesion kinase (FAK), which is known to directly bind members of the integrin adhesion molecules. Here we have used fascin loss and gain of function approaches to examine if fascin influences integrin expression to regulate breast CSC function. Our results have demonstrated that fascin expression in breast cancer cells is directly associated with increased expression of integrins including: CD49a, CD49C, CD49f, CD29 and CD61. Fascin-mediated integrin expression on breast cancer cells enhances their adhesion, chemoresistance and tumorsphere formation ability. This study supports a role for fascin in the maintenance of breast CSCs via the regulation of integrin expression. The outcome of this study is expected to provide another evidence that fascin targeting may present a new approach for optimal treatment of breast cancer from the root.

  • Cell-based therapy using miR-302-367 expressing cells represses glioblastoma development
    Speaker
    Thierry Virolle
    Institut de Biologie Valrose- Ibv
    France
    Biography

    Thierry Virolle is a Research Director (permanent position) at Institut National de la Santé et de la Recherche Médicale (INSERM), Head of the Team Cancer Stem Cell Plasticity and Functional intra-tumor Heterogeneity at the Institute of Biologie Valrose (iBV). He is Co-Founder of the French National Sud Cancer Stem Cell Network, SUNRiSE dedicated to the study of cancer stem cell.

    Abstract

    Glioblastomas are incurable primary brain tumors that affect patients of all ages. The aggressiveness of this cancer has been attributed in part to the persistence of treatment-resistant glioblastoma stem-like cells (GSC). We have demonstrated that microRNA cluster miR-302-367 has the potential to force GSC exit from stemness, promoting loss of stemness properties and tumorigenicity and revealing a great therapeutic interest. In our study we attempt to develop a cell-based therapy for miR-302-367 continuous delivery by taking advantage of the capability of glioma cells to secrete exosomes that enclose small RNA molecules. We engineered primary glioma cells to stably express the miR-302-367. Remarkably, these cells altered, in a paracrine manner, the expression of stemness markers, the proliferation and the tumorigenicity of neighboring glioblastoma cells. Further characterization of the secretome derived from miR-302-367 expressing cells showed that a large amount of miR-302-367 was enclosed in exosomes, which were internalized by the neighboring glioblastoma cells. This miR-302-367 cell-to-cell transfer resulted in the inhibition of its targets such as CXCR4/SDF1, SHH, cyclin D, cyclin A and E2F1. Orthotopic xenograft of miR-302-367-expressing cells together with glioblastoma stem-like cells efficiently altered initiation and tumor development in mice brain.

Poster
Chair
Speaker
  • Overexpression of cofactor of BRCA1 in HepG2 Cells: A step towards understanding the role of COBRA1 in hepatocellular carcinoma
    Speaker
    Asma Amleh
    American University in Cairo
    Egypt
    Biography

    Razan Masad is a researh associate at the cell therapy center in Jordan. She has a keen interest in cancer and stem cell research. She received a BSc in medical laboratory sciences from the Hashemite University, Jordan (2006), and a MSc in bioechnology from the American University in Cairo, Egypt (2017). Masad has joined Amleh research team in September 2015, where she conduced her MSc research under the guidness of professor Asma Amleh, an associate professor of biology at The American University in Cairo. The aim of her thesis project was to investigate the role COBRA1 plays in the tumerogenesis of hepatocellular carcinoma. Prior to completing her master’s degree, Masad worked as a medical laboratory technologist at Medlabs Consultancy Group in Jordan.

    Abstract

    Cofactor of BRCA1 (COBRA1) is a BRCA1 interacting protein that represents one of the four subunits of the negative elongation factor (NELF) complex. NELF is known by its ability to stall RNA Polymerase II during the early phase of transcription elongation, resulting in repressed transcription of several genes including ones associated with tumorigenesis of different cancer types. While it was found to be down-regulated in breast cancer, COBRA1 was found to be up-regulated in the upper gastrointestinal carcinoma and hepatocellular carcinoma (HCC). In the current study, we aimed to elucidate the significance of COBRA1 overexpression in HCC further. HepG2 cells were transfected with a pCMV5-HCOBRA1 plasmid. The ectopic expression of COBRA1 was confirmed at the RNA and protein levels. The cells proliferation and migration following COBRA1 overexpression were assessed using the trypan blue dye exclusion method and the wound-healing assays respectively. The semi-quantitative RT-PCR was used to analyze the expression of mRNA steady-state levels of COBRA1, the remaining NELF subunits, TFF1 and TFF3 genes, as well as other tumorigenesis related genes. Our results revealed that COBRA1 transfected cells exhibited a comparable proliferation and migration rates to non-transfected cells. These results were accompanied by an insignificant effect of COBRA1 overexpression on the levels of the proliferation marker; Ki-67 and the anti-apoptotic gene; survivin. Also, the mRNA levels of the other NELF subunits, TFF1 and TFF3 were found to be comparable among all the tested groups. Collectively, our results suggest that the proposed involvement of COBRA1 in HCC is supported by and dependent on the assembly of the active NELF complex, which requires the expression of all four NELF subunits. Moreover, COBRA1 mediated role in HCC tumorigenesis might be due to mechanisms and regulatory pathways other than the ones examined here. However, further studies are required to confirm these notions.

  • Cancer stem cells in metastatic colon adenocarcinoma to the liver
    Speaker
    Swee T Tan
    Gillies McIndoe Research Institute
    New Zealand
    Biography

    Swee T Tan is the Director of the Gillies McIndoe Research Institute in Wellington, New Zealand. He completed his Medical Training at Melbourne University in 1985, Plastic Surgery Training in New Zealand in 1992, and gained a PhD from Otago University in 2001. In 1995, he was appointed as Consultant Plastic & Cranio-Maxillofacial Surgeon at the Wellington Regional Plastic, Maxillofacial & Burns Unit at Hutt Hospital, where he was the Director of Plastic Surgery from 2000 to 2006 and Director of Surgery 2007-2013. He was appointed as Professor in Plastic Surgery at Otago University in 2008. He is the Founder and Director of the Centre for the Study & Treatment of Vascular Birthmarks, a national referral centre. He has received numerous honours and awards and is well known internationally for his research into the stem cell basis of diseases including vascular anomalies and cancer. He is the author of more than 140 publications and has delivered over 350 lectures at conferences.

    Abstract

    Introduction: Colorectal cancer (CRC) is the third most common cancer in the USA. Approximately 20% of CRC patients present with synchronous liver metastasis at the time of diagnosis and overall 50% develop liver metastasis during the course of their disease. The median survival of CRC patients with liver metastasis (CRCLM) is 5-20 months if left untreated. This study aimed to identify and characterise the CSC population in CRCLM using OCT4, SOX2, NANOG, c-Myc and KLF4. Methodology: DAB immunohistochemical (IHC) staining was performed on six CRCLM samples for OCT4 SOX2, NANOG, c-Myc and KLF4. Immunofluorescent (IF) IHC staining was performed to investigate co-expression of markers. Nanostring in situ hybridisation (ISH) mRNA analyses was performed for the transcriptional activation. Cell counting was performed on IHC and ISH stains. ?2 test and the t-tests were used for statistical analysis to compare the cells within the tumour nests (TNs) and those within the peritumoural stroma (PTS). Results: IHC staining demonstrated the expression of OCT4 SOX2, NANOG, c-Myc and KLF4 within CRCLM. IF IHC staining showed the presence of three CSC: (i) SOX2+/NANOG+/KLF4+/cMYC+/OCT sub population within the TNs; (ii) SOX2+/NANOG+/KLF4+/cMYC+/OCT4- sub population and (iii) SOX2+/NANOG+/KLF4+/cMYC+/OCT4+ sub population, in PTS. Nanostring transcriptional demonstrated the expression for all markers, except for SOX2. ISH confirmed the expression for all the markers. Conclusion: This study demonstrates 3 putative sub-populations of CSCs within CRCLM: one within the TNs and two in PTS. OCT4 was only observed in the CSC subpopulation within the PTS, offering novel insights into the biology of this cancer.

  • MAC induces apoptosis via Inhibition of c-Myc and AMPK/mTOR dependent pathway in leukemia cells
    Speaker
    Young-Chae Chang
    Catholic University of Daegu School of Medicine
    South Korea
    Biography

    Young-Chae Chang is a Professor at the department of cell biology in the Catholic University of Daegu School of Medicine, Korea. He received his BS and MS from Yeungnam University, Korea and obtained his PhD dgree in a cell biology from University of Tokyo, Japan in 1995. He then carried out Postdoctoral training at National Institute of Bio-Science and Human Technology, Japan and University of Vermont college of Medicine, USA for 5 years. He has published more than 120 scientific papers in reputed journals. His lab is currently studying the molecular mechanism of signal transduction in tumorigenesis and metastasis control.

    Abstract

    The expression of c-Myc closely correlated with the tumorogenesis, cell proliferation, differntiation, and cell death. In this study, we provide evidence for the 4-O-methyl-ascochlorin (MAC), which is a methylated derivative of the prenyl-phenol antibiotic ascochlorin, is an anti-cancer agent of leukemia that induces cell death via own regulation of c-Myc protein expression. Although the effects of MAC on apoptosis have been reported, the underlying mechanisms remain unknown. In the present study, we show that MAC promoted apoptotic cell death and downregulated expression of c-Myc in K562 human leukemia cells. The effect of MAC on apoptosis was similar to that of 10058-F4 (a c-Myc inhibitor) or c-Myc siRNA, suggesting that the downregulation of c-Myc expression plays a role in the apoptotic effect of MAC. Further investigation showed that MAC downregulated c-Myc by inhibiting protein synthesis. MAC promoted the phosphorylation of AMP-activated protein kinase (AMPK) and inhibited the phosphorylation of mammalian target of rapamycin (mTOR) and its target proteins, including p70S6K and 4EBP1. Treatment of cells with AICAR (an AMPK activator), rapamycin (an mTOR inhibitor), or mTOR siRNA downregulated c-Myc expression and induced apoptosis to a similar extent to that of MAC. These results suggest that the effect of MAC on apoptosis induction in human leukemia cells is mediated by the inhibition of c-Myc protein synthesis via an AMPK/ mTOR-dependent mechanism.

  • Cancer stem cells in renal clear cell carcinoma
    Speaker
    Tinte Itinteang
    Gillies McIndoe Research Institute
    New Zealand
    Biography

    Tinte Itinteang serves as the current Chief Scientific Officer and the Evans Family Research Fellow of the Gillies McIndoe Research Institute (GMRI) in Wellington, New Zealand. He completed his Medical Training at the Melbourne University in 2001, and then completed his Basic Medical Residency in New Zealand, from 2008-2010. He completed his PhD from Victoria University of Wellington, NZ on the role of stem cells and the renin-angiotensin system (RAS) in infantile haemangioma. From 2012-2014, he was appointed as a Research Fellow at the Gillies McIndoe Research Institute, during which he spent six weeks at the Friedlander laboratory at The Scripps Research Institute in San Diego investigating the role of iPSCs for disease modelling. He was then appointed as the Chief Scientist of the GMRI from 2015. His work on the role of stem cells and the RAS in infantile haemangioma has been acknowledged with the International Society for the Study of Vascular Anomalies John Mulliken award as well as several national and international honours. He is the author of over 50 peer reviewed articles and has given over 100 presentations at international conferences.

    Abstract

    Introduction & Aim: Renal cell carcinoma is the ninth most common cancer worldwide, with renal clear cell carcinoma (RCCC) making up 80-85% of these. Current treatment for RCCC involves nephrectomy with 40% developing a recurrence with an overall 5-year survival rate of 10%. This study aimed to characterise these CSCs. Methodology: DAB immunohistochemical (IHC) staining was performed on six CRCLM samples for CSC markers OCT4, SOX2, NANOG, c-Myc and KLF4. Immunofluorescent (IF) IHC staining was performed to investigate the co-expression of two markers. NanoString and in situ hybridisation (ISH) mRNA analyses were performed for transcriptional expression. Cell counting was performed on the IHC and ISH stains and the t-tests for statistical analysis. Results: DAB IHC staining demonstrated the expression of all 5 CSC markers in RCCC, and supported by NanoString and ISH analyses. IF IHC staining demonstrated the co-expression of OCT4 in a proportion of the SOX2+/NANOG+/KLF4+ populations. Furthermore the co-expression of KLF4 was also demonstrated in a proportion of the SOX2+/NANOG+/KLF4+ population. Cell counting demonstrated a high abundance of NANOG (86%), SOX2 (83%) and c-Myc (80%), with lower counts for KLF4 (15%) and OCT4 (8%). Conclusion: This study shows a range of CSC sub populations within RCCC with a less abundant OCT4+/c-Myc+/SOX2+/NANOG+ sub population and a KLF4+/c-Myc+/SOX2+/NANOG+, this is supported by relatively low abundance of OCT4+ and KLF4+ cells. These novel findings support the presence of potentially two subpopulations of CSCs within RCCC, although equally as likely is that the OCT4+ cells are a subset of the KLF4+/c-Myc+/SOX2+/NANOG+ cells.

  • Tumor microenvironment with breast cancer cells promoted invasion and tube formation of endothelial colony forming cells (ECFC)
    Speaker
    Aree Moon
    Duksung Women’s University
    South Korea
    Biography

    Aree Moon is a Professor at College of Pharmacy, Duksung Women’s University. She received her BS degree at College of Pharmacy, Seoul National University, Seoul, Korea in 1983. She moved to the USA and continued to study in Biochemistry. She got her PhD degree at Department of Biochemistry and Biophysics, Iowa State University, Iowa, USA in 1989. Since 1995, she has been a Professor at College of Pharmacy, Duksung Women’s University. She has received a number of awards including The Presidential award, The Order of Science and Technology Merit and the Korea L’Oreal-UNESCO Award for woman in science.

    Abstract

    The tumor microenvironment is recognized as a key factor in multiple stages of cancer progression, immune-escaping, and distant metastasis. Endothelial colony forming cells (ECFC) is the circulating endothelial precursor that contributes to building new blood vessels in adult body. Here, we investigated the effect of surrounding breast cancer cells on invasive phenotype and angiogenic property of ECFC by using co-culture systems. In the indirect co-culture system with MDA-MB-231 breast cancer cells, invasion phenotype of ECFC was significantly increased compared to the cells cultured alone. Tube formation of ECFC was enhanced by direct co-culture with MDA-MB-231 cells. Taken together, the present study suggest that the interaction with breast cancer cells may promote aggressiveness of ECFC.

  • A study of the mechanisms of cells apoptosis mediated through tissue factor-?1-integrin complex formation
    Speaker
    Faisal Alahaydib
    University of Hull
    United Kingdom
    Biography

    Biography

    Abstract

    ?1-integrin is a subunit of integrin complex, which belongs to transmembrane protein. ?1-integrin binds with tissue factors in ECM, leading to cell adhesion and proliferation. It has a role in platelets adhesion and aggregation with endothelial cells during haemostasis. However, hyperactivation of ?1-integrin involves in cancer spread and metastasis. In contrast, apoptosis can be induced by blocking ?1-integrin via switch Src1 activity, through activation of P38, MAPK and P53-mediated cell apoptosis. So, targeting ?1-integrin is important for developing anticancer drugs.

  • Detection of Janus kinase 2 (JAK2V617F) in sudanese patients with polycythemia in Khartoum state, Sudan
    Speaker
    Mouhanad Adam
    Alzaiem Alazhari University
    Sudan
    Biography

    Mouhanad Adam has completed his MSc from Alzaiem Alazhari University. He is the Director of Alshamel Clinical Lab. He was awarded a Master’s degree in Hematology and blood transfusion with grade very good. He is very interested in the molecular and hematological studies as general.

    Abstract

    Background & Aim: Erythrocytosis is form of hematological diseases, the main members of which are polycythemia vera (PV) , familial polycythemia and idiopathic erythrocytosis. The molecular pathogenesis of these disorders is unknown, but tyrosine kinases have been implicated in several related disorders. We investigated the presence of the cytoplasmic tyrosine kinase JAK2 in patients with polycythemia and the hematological difference between these types in Sudanese patients. Methods: We measure the full blood counts and obtained DNA samples from patients with erythrocytosis. The JAK2V617F mutation was detected from peripheral-blood samples. Allele-specific PCR were undertaken on subgroups of patients who satisfied the WHO criteria of polycythemia vera. Results: A single point mutation (V617F) was identified in JAK2 in 31 (54.4%) of 57 patients with polycythemia and there are no significant differences of hemoglobin, hematocrit, and neutrophil between patients with the JAK2 mutation and who without the mutation. Polycythemia vera patients who are not detected for the mutation and patients with idiopathic erythrocytosis showing no difference except in platelet's count . Interpretation: A single mutation of JAK2V617F was noted in more than half of patients with erythrocytosis. If the person is negative for JAK2V617F mutations, the person may still have a PV. The person could have a JAK2 exon 12 mutation which was not detected during research.

Mail us at

Drop us an email for Program enquiry
cancerstemcells@alliedconferences.org
Sponsors/Exhibiting/Advertising
cancerstemcells@alliedconference.com
General Queries
cancerstemcells@alliedconferences.org
More details about sponsorship:sponsors@alliedacademies.com

Terms and Conditions

Cancellation, Postponement and Transfer of Registration

All cancellations or modifications of registration must be made in writing to finance@conferenceseries.com

Cancellation Policy

If Allied Academies cancels this event for any reason, you will receive a credit for 100% of the registration fee paid. You may use this credit for another event which must occur within one year from the date of postponement. 


Postponement


If Allied Academies postpones an event for any reason and you are unable or unwilling to attend on rescheduled dates, you will receive a credit for 100% of the registration fee paid. You may use this credit for another event which must occur within one year from the date of postponement.

 

Transfer of registration

All fully paid registrations are transferable to other persons from the same organization, if registered person is unable to attend the event. Transfers must be made by the registered person in writing to finance@conferenceseries.com. Details must be included the full name of replacement person, their title, contact phone number and email address. All other registration details will be assigned to the new person unless otherwise specified.

Registration can be transferred to one conference to another conference of Allied Academies if the person is unable to attend one of conferences.

However, Registration cannot be transferred if it is intimated within 14 days of respective conference.

The transferred registrations will not be eligible for Refund.


Visa Information

Keeping in view of increased security measures, we would like to request all the participants to apply for Visa as soon as possible.

Allied Academies will not directly contact embassies and consulates on behalf of visa applicants. All delegates or invitees should apply for Business Visa only.

Important note for failed visa applications: Visa issues cannot come under the consideration of cancellation policy of Allied Academies, including the inability to obtain a visa.

Refund Policy

If the registrant is unable to attend, and is not in a position to transfer his/her participation to another person or event, then the following refund arrangements apply:

Keeping in view of advance payments towards Venue, Printing, Shipping, Hotels and other overheads, we had to keep Refund Policy is as following slabs-

  • Before 60 days of the conference: Eligible for Full Refund less $100 service Fee
  • Within 60-30 days of Conference: Eligible for 50% of payment Refund
  • Within 30 days of Conference: Not eligible for Refund
  • E-Poster Payments will not be refunded.

Accommodation Cancellation Policy:


Accommodation Providers (Hotels) have their own cancellation policies, and they generally apply when cancellations are made less than 30 days prior to arrival. Please contact us as soon as possible, if you wish to cancel or amend your accommodation. Allied Academies will advise the cancellation policy of your accommodation provider, prior to cancelling or amending your booking, to ensure you are fully aware of any non-refundable deposits.

Highlights from last year's Convention

Authorization Policy


Copyright © 2018-2019 Allied Academies, All Rights Reserved.