Day 1 :
- Breast Immunotherapy
Briacell Therapeutics, USA
Title: Targeted Immunotherapy for Breast Cancer Immunotherapy - Fact, myths and experience: Mythbusters: How beautiful facts can falsify ugly theories
Time : 10:00-10:50
Charles Wiseman is Clinical Professor of Medicine at the Division of Medical Oncology, Keck-USC School of Medicine, and previously was Acting Chief of the Division of Oncology/Hematology at White Memorial Medical Center. Dr. Wiseman has been cited in US News Top Doctors yearly since 2002. He brings more than 40 years of academic and clinical experience to Bria Cell Therapeutics Corp. As Co-Founder of Bria Cell, he is the inventor for most of the Company’s intellectual property and actively participates in its ongoing technology development. As the former Director of the Breast Cancer Basic Research Laboratory at the University of Texas M.D. Anderson Hospital in the 1970s, he was one of the pioneers of the field of cancer vaccine therapeutics. He has written in over 100 peer-reviewed publications and medical textbook chapters.
In the 70’s, there was great excitement about the promise of BCG to as a new approach to treating many cancers, breast cancer included. That idea didn’t prove true, as did many widely held concepts. We have come a long way in the past 50 years, and it should be helpful to pay some attention to the developments that led us to the current state. The recent positive results with the SV-BR1-GM targeted therapy stand in contrast to some of the previous ‘widely held concepts’; During the discussion, I will discuss objective findings that refute the following:
Breast cancer is not immunogenic
Targeted Immunotherapy is effective only if <10^6 cells
BCG can aid tumor regression and extend survival
Chemotherapy is immunosuppressive and would neutralize any immunotherapy benefit
The brain is a privileged site,
Responses to immunotherapy are very slow
Considering some of the past perspectives, with my discussion of the positive results of my own work and that of others, I will offer a few speculations and discuss some unsolved challenges to developing an effective therapy for breast cancer.
Oncompass Medicine Hungary Ltd., Hungary
Anna Sipos is completing her PhD in Pharmaceutical Sciences at the Semmelweis University, Budapest, Hungary. She has a research practice of over 10 years working in EU universities on projects related to cancer research and immunological disorders. She has published more than 12 papers in reputed journals and presented more than 9 abstracts at prestigious national and international conferences. Currently, she is a Research Biologist at Oncompass Medicine Hungary Ltd. Her research interests are focused in the DNA damage repair processes, molecular diagnostic and biomarkers of cancer.
Breast cancer is the most frequent cancer among women and responsible for approximately 15% of all their cancer deaths. Approximately 20% of patients with early-stage HER2-positive breast cancer can benefit t from Herceptin (trastuzumab) therapy which was approved by FDA in 2006. Therefore, an early diagnosis of biomarkers is a critical factor in breast cancer therapy. The Oncompass Medicine Hungary Ltd., as a member of the ADMONT – “Advanced distributed Pilot Line for More-than-Moore Technologies” project aimed to develop a novel diagnostic platform for detection of HER2-positive circulating tumor cells (CTCs) from blood next to the patient’s bed. The platform design based on the lab-on-chip solution is supported by MtM (More-than-Moore) technology. LED-based photodetectors observes the colorimetric response of CTCs with different level of HER2 expression. Commercially available CTC isolation method was optimized to improve CTC yield from blood-based cellular model system and patient derived material. An alkaline phosphatase-based (AP) detection system was set on blood-based cellular breast cancer model system to assess the sensitivity of the detector arrays and meet the characteristics of the prototype device. Our developments introduce a unique integrated diagnostic system that is faster, cost-effective and requires less number of cells or sample material than conventional techniques such as flow cytometry (FACS), fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). As a novel molecular diagnostic system for personalized medicine, it enables detection of HER2-expression to select patients for cancer therapy and also screening of therapy response, based on a less-invasive and easily repeatable sampling. The research leading to these results has received funding from NEMZ_15-1-2016-0002 project.
Universite Badji Mokhtar, Algeria
Rim Bouchelaghem is pursuing her PhD in Biochemistry and Environmental Toxicology Laboratory at University Badji Mokhtar in Annaba (UBMA), Algeria. Her research concentrates on the discovery of biomarkers in breast cancer. She has completed her Doctoral degree in Medicine from UBMA, and her MSc degree in Immunology from University de Sherbrooke (UdeS), Canada. She is working on Molecular Analysis at the anatomopathology section of the Anti-Cancer Center (CAC) Abdelaziz Al Saoud of Annaba.
Breast cancer is considered the leading cause of death for women worldwide. Currently, the characterization of biomarkers for subtypes of breast cancer is an urgent requirement that makes it possible to better optimize the consensus of diagnosis and treatment of this disease in more homogeneous subgroups. Pre-clinical exploratory studies to identify potential candidates as tumor biomarkers are considered the first step to refi ne the research of such molecules. Many members of the G protein-coupled receptors family (GPCRs) are known for their implication in breast cancer progression and metastasis. In our study, we aim to verify the role of intracellular signaling induced by Apelin peptide jejunum (APJ), a GPCR, as a new modulator of growth signaling in the breast cancer cell line, MCF-7. We confirmed for the first time the constitutive expression of the APJ receptor in MCF-7 by two different techniques, immunocytochemistry, and confocal microscopy. Also, we explored the effect of APJ activation by its specific ligand, apelin-13, on the AMP-activated protein kinase (AMPK), which is known in the literature for its antiproliferative effect on MCF-7 cell line. MCF-7 cells were treated for 5, 10, 20, 30 or 60 minutes with 100 nM apelin-13, in the presence or the absence of 1 nM estrogen. We verified by immunoblotting that apelin-13 decreases the constitutive AMPK activity in a time-dependent manner. Our results confirm that, the activation of APJ in MCF-7 by apelin-13 and suggest a proliferative role of this hormone, at least by the abrogation of the AMPK signaling pathway. Our study will provide a new trail in the understanding of the molecular mechanisms involved in breast carcinogenesis, a prerequisite for the development of targeted therapies against this complex disease.
Silbiotech Inc., USA
Numerous clinical studies have established that diagnosis of hyperplastic masses increases the cancer risk by 2-5 fold. Clinical follow-up surveys have shown that ~20% and 10% of subjects diagnosed with atypical and non-atypical hyperpalsias respectively develop cancer subsequently and are the most suitable candidates for preventative therapies. However, there are no methods for identifying the above high risk subjects who will most likely develop future cancers and benefi t from prophylactic measures. Due to lack of any risk stratification tools, healthcare providers as well as patients are faced with a dilemma in undertaking preventative measures. Our study purpose is to investigate a four marker risk signature, MMP-1, CEACAM6, HYAL1 and HEC1, using 440 hyperplastic tissues with up to 19 years of clinical follow-up information for risk stratifi cation and identifying high risk subjects who will benefit from preventative therapies. We have assayed the marker levels in the hyperplasia tissues and combined their expression levels to obtain a composite value from 0-10 which we called a ‘Cancer Risk Score’. We demonstrate that the four marker based risk scores predict subsequent cancer development with an accuracy of 91% and 86% for atypical and non-atypical subjects respectively. We have established a correlation between risk scores and cancer rates at 5 years, 10 years and beyond by stratifying the samples into Low (Score < 0.5), Intermediate (Score <= 5.4) and High (Score > 5.4) risk groups and Kaplan Meier survival analysis. Our results show that the cancer rates in the first five years among the low-, and intermediate risk groups were 2%, and 15% respectively among atypical as well as non-atypical subjects. In the high risk group, the cancer rates were 73% and 34% for atypical and non-atypical subjects respectively. The molecular risk stratify cation developed by us assesses a patient’s tumor biology based risk level in terms of a cancer risk score and categorizes the patient as low-, intermediate- or high risk for making informed treatment decisions (Figure 1). Th e outcomes of our study in conjunction with the already available prophylactic measures could prevent ~20%-25% of sporadic breast cancers (Grant Support: National Cancer Institute, National Institutes of Health (CA173919 and CA206774) and the National Science Foundation (IIP-1314287) awarded to I. Poola).
Indira Poola has completed her PhD in Biochemistry from Mysore University, Mysore, India and post-doctral training at the University of Michigan and Cornell University in the USA. She served as a Professor in Biochemistry and Molecular Biology and Surgery at Howard University Medical School, Washington, D.C. USA for 17 years. She is currently President of Silbiotech, Inc, in Gaithersburg, MD, USA. She has won 27 grant awards from 9 funding agencies totaling over $8Million. She has published more than 40 papers in highly reputed journals and has served as an adhoc reviewer for 24 journals. She has served as an adhoc grant reviewer for 10 different agencies including NIH, DoD, NSF, EPA, and Komen for the Cure.
Gaia Holistic Health, USA
Kazuko Tatsumura has completed her graduation from Toho Academy of Music in Tokyo, as a Pianist and Composer. She has invited by the Boston Symphony orchestra. She came to the USA in 1961 as one of the first Japanese women. She then received Master of Art from New York University and fi nished her PhD credits in Philosophy in 1965 and another PhD and OMD from the International Academy of Education in Tokyo in 2000. In 1967, she has turned to an independent career and became the top International Classical and Cultural Impresario/producer. Until 1992, she has conducted an average of 2,000 cultural events per year travelling to more than 140 countries. She was presented with numerous honors for her work from different countries, many for humanitarian causes. She has studied Oriental Traditional Medicine of Japan, Korea, Taiwan and China. She established the Oki-Do Holistic Health Center in 1994 in NY and in 2001 the GAIA Holistic Center (501C3 nonprofi t organization) at the wake of 9/11 tragedy, for body mind and spirit, aiming for the noninvasive natural healing methods based on the wisdom of the East. She has written numerous articles and several books. She is well known as a Philanthropist.
Introduction: Onnetsu means comfortable heat. Onnetsu Th erapy invented by Dr. Kazuko Tatsumura emits from a special patented ceramic; 1) Heat 2) Precise 8-10μ of vibration of Far Infrared Sunray and 3) Vibration of Terahertz. Tatsumura is the first in the world to incorporate Terahertz minerals to medical use from active volcanos stones from Japan. Worldwide patent pending.
Methods: When Onnetsuki is slid over the skin, healthy areas are comfortable, but IF deep tissue is unhealthy or cold, degenerated, patient feels this spot to be ‘hot’. When this ‘hot spot’ is eff ectively treated with Onnetsu Th erapy (Far-Infrared & Terahertz vibrations, and Heat), the hot sensation subsides and the Disease conditions improve through vibrating water molecules of our deep tissue. Th erefore, the Onnetsu Th erapy is both a diagnostic and therapeutic.
Dr Kazuko’s Onnetsu Th erapy is based on four historical and scientifi c facts.
- Traditional Japanese Concept of the signifi cance of Body Temperature. Hippocrates also has left quotes on Heat.
- NASA's fi nding regarding Far-Infrared vibration from Sun light precise 8-10μ. Also, added is the specific c Terahertz vibration of earth minerals from volcanos stones from the depth of our planet earth.
- Immunology by Dr. Toru Abo, balancing autonomic nervous system to improve Condition of white cells; Raising Immunity.
- Promoting four flows of Energy throughout our body by using acupuncture meridian Technique.
Result: Some countries (Peru, Cuba & Mexico) are practicing it in the hospitals and clinics. Clinical trials have shown improvements on many diseases: such as asthma, brain, ear & eye Problems, cancers, diabetes, rheumatoid arthritis, tuberculosis and various pain conditions. Clinical studies from Cuba and Peru will be presented.
Conclusion: Onnetsu Therapy is a new, easy & non-invasive treatment modality to treat difficult chronic medical conditions. Therapy uses Universal Vibrations, Heat, Light, Autonomic Nervous System Balance and Acupuncture Meridian System.
Prince of Songkla University, Thailand
Keson Trakunram received her both Bachelor’s (Biotechnology) and Master’s (Pharmacology) degrees form Faculty of Science, Prince of Songkla University (PSU). Presently, she is a philosophy student at Department of Biomedical Sciences, Faculty of Medicine, and PSU. According to her thesis, she is interested in microRNAs expression leading to diagnostic biomarkers in lung cancer. Major scope of her study focuses on serum microRNA profiling using microarray and bioinformatics tools. Moreover, she has published about two papers and one international proceeding.
MicroRNAs (miRNAs), small non-coding RNA, play important role as negative regulation of gene expression. Deregulation of miRNAs has been used for predicting cancer progression in various cancers, including non-small cell lung cancer (NSCLC). Therefore, searching for potential non-invasive biomarkers is need for rapid diagnosis of lung cancer. This study aimed to evaluate whether serum miR-339-3p can be a diagnostic biomarker for NSCLC. A retrospective study was designed. Serum was collected from 151 suspected patients with lung cancer. All patients were diagnosed at Songklanagarind Hospital (Hat Yai, Thailand), a university hospital in Southern Thailand, between December 2017 and September 2018. Expression of miR-339-3p was determined by quantitative real-time PCR (qRT-PCR) technique. Receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to test the diagnostic performance. Result showed that 66 patients were NSCLC and 85 patients were non- NSCLC. The mean relative expression of serum miR-339-3p in NSCLC patients was approximately two times higher compared with that of non-NSCLC patients with P-value of 0.009. In addition, the ROC curve data indicated that this serum miR-339-3p can distinguish the NSCLC patients from the non-NSCLC patients with the AUC of 0.624 (95% CI: 0.53-0.71). The sensitivity was 73% and the specificity was 45%. In conclusion, serum miR-339-3p may serve as a circulating biomarker for diagnosis of lung cancer.
Dokuz Eylul University, Turkey
Aylin Erol has completed her MSc from Basic Oncology at Dokuz Eylul University, Turkey. Currently, she is pursuing her PhD at the Dokuz Eylul University. She has published four papers with the project group and also, had one oral presentation. Her work focuses specifically on the anti-cancer natural products for pediatric cancers.
Despite improvements in treatment of pediatric cancers, new treatment strategies are needed. Sesquiterpene lactones (SL) are natural compounds with proofs of anticancer effects in adults. The effect of SL on pediatric cancers remains unclear. The aim of this study is to evaluate the in vitro effects of dehydroleucodine (DhL) and Inula viscosa extracts (containing high levels of active SL) in pediatric cancers. Inula viscosa plant extract (InV), DhL (sigma) and cisplatin (Kocak) (CDDP) were evaluated on various pediatric cell lines. Neuroblastoma cell line KELLY, Ewing sarcoma cell line SK-ES and hepatocellular carcinoma cell line Hep-G2 were cultured. After treating with these chemical compounds, MTT cell viability assay, Annexin V+PI test by flow cytometry were performed. Morphological changes of cells were investigated using Toluidine blue staining. Immunohistochemistry was performed to determine proliferation index (Ki67) and apoptosis mechanisms (Caspase 3, 8 and 9). The statistical analysis of all findings was evaluated between and within groups by Mann-Whitney U test. The p value less than 0.05 were considered statistically significant. In Kelly, DhL and InV showed cytotoxic effect as CDDP. The underlying mechanism of this effect was on inducing apoptosis rather than anti-proliferation. In HEP-G2; CDDP, InV, and DhL decreased proliferation, led to apoptosis especially via intrinsic pathway. For SK-ES; DhL and InV showed less anti-proliferative effect than CDDP. However, remarkable apoptosis percentiles were found in cells. According to the results of this in vitro study, InV, and DhL are found to be candidate anti-cancer agent on pediatric cancer cells with their cytotoxic effects. This effect is planned to be evaluated in further studies.
Addis Ababa University, Ethiopia
Workinesh Daba Seboka has completed her BSc degree from School of Nursing and Midwifery, Addis Ababa University and Master of Public Health in Reproductive and Family Health from School of Public Health, Addis Ababa University. She is a Lecturer at Addis Ababa University - College of Health Sciences, School of Nursing and Midwifery. She has six years of work experience and an expert Midwife Professional.
Background: A diagnosis of breast cancer regardless of the stage can be stressful, impact multiple spheres of life, and disrupt physical status, emotional and spiritual well-being, and personal relationships for the patient and family. In order to adapt, the patient ought to employ certain coping mechanisms.
Objectives: The objective of the study is to assess the coping strategies of women with breast cancer in Black Lion Hospital, Oncology Department.
Methods: An institutional cross sectional survey was employed to collect data on coping strategies of women with breast cancer seeking care at Black Lion Hospital, Oncology Department, Addis Ababa, Ethiopia from March to April, 2016. A structured interviewer administered questionnaire was used to collect information from study participants. The data collection process was guided by an interviewer to gather information from the study participants. Data coding, entry and cleaning was accomplished using EpiData3.1 after which it was exported to SPSS version 23 for analysis.
Results: The results of this study showed the most commonly used coping strategies among women with breast cancer seeking care at Black Lion Hospital were self-distraction, planning, behavioral disengagement, and religion. It was found that coping with breast cancer was significantly associated with age less than 49 years which is five times more likely than with age greater than 50 years (AOR=4.582; CI=95%: 1.532-13.699). Married women were four times more likely to cope with breast cancer compared to unmarried women (AOR=3.601; CI=95%: 1.434-9.044). Being educated secondary school and above is associated four times more likely to cope with breast cancer than illiterates.
Conclusion: A diagnosis of breast cancer causes stress to the patients. Predominant coping strategies used were: self-distraction; planning; behavioral disengagement; and religion. The strategy employed influences adaptation to the diagnosis.
University of Valencia, Spain
Valentina Dikova has completed a BSc degree in Biology and Chemistry followed by a MSc grade in Molecular Cell and Developmental Biology obtained from the University of Innsbruck, Austria. Postgraduate was assigned as a biomedical researcher in a H2020 supported MitoFit Project where she acquired experience in developing novel laboratory standards and diagnostic monitoring of cellular bioenergetics studding mitochondrial functions and disease related impairment. Since March 2017 has been recruited in the University of Valencia, Spain as a Marie Sklodowska Curie PhD fellow carrying out an investigation of molecular biomarkers with clinical application in cancer research.
Oral Squamous Cell Carcinoma (OSCC) is a common human malignancy with poor survival rates associated with the late diagnosis and frequent recurrences. It develops through a multistep process where the initial presence of a precursor cell subsequently evolving into a tumor outgrowth is well established. Furthermore, a complex of genetic and epigenetic metabolic changes has been correlated to the cancerous transformation of oral potentially malignant disorders (OPMD) such as Oral Leukoplakia (OL). Since inflammation has been linked to the pathology of OSCC, research to date indicates the possibility of using salivary pro and anti-inflammatory factors for screening of oral disorders. Therefore, a prospective study to determine novel molecular biomarkers is carried out addressing current clinical needs with diagnostic & prognostic means. Multiplex immunoassay enabled simultaneous detection and quantitation of a protein panel including IL-1α, IL-6, IL-8, IP-10, MCP-1, TNF-α, HCC-1, PF-4 and MIP-4 in saliva samples obtained from 86 volunteers (mean age 64.4±3.86 years) classified into Control, OL, Early and Advanced stage of OSCC groups. Analysis showed significantly elevated concentrations of IL-6, IL-8, IL-10, TNF-α, HCC-1, MIP-4 and PF-4 according to the oral cancer progression (Fig.1A,B). Besides, MCP-1 and PF-4 were found importantly higher in pre-cancerous condition collated to controls, while IL-8 and PF-4 demonstrated a trend towards a growth among patients diagnosed with OL and OSCC (Fig.2A, B). The results suggest that saliva can be used as a promising diagnostic fl uid where measureable parameters like cytokines and chemokines at differential levels can discriminate disease process and have a prognostic value.
Prince of Songkla University, Thailand
Pritsana Raungrut, received her PhD degree in Faculty of Medicine from Prince of Songkla University (PSU). According to her thesis, she is focused on lung cancer (i.e., in order to find predictive markers for detection, diagnosis, or prognosis for lung Cancer). Major scope of her study focuses on mechanism of cancer progressions and management of cancer etc.
14-3-3γ has been shown to be involved in the metastasis of lung cancer; however, its functional roles regarding an ability of tumor cell invasion are still unclear. In this study, the roles of 14-3-3γ in migration and invasion were investigated using NSCLC cells. The constructed 14-3-3γ expression vector was used to increase the expression level of 14-3-3γ. Expression levels of proteins were detected by western blotting. Cellular migration and invasion was analyzed using 2D/3D wound healing model and Trans well assay. The wound healing assay revealed that the closing rate of scratch wounds in invasion was significantly increased in 14-3-3γ-overexpressing cells compared with the non-transfected cells (33%, P=0.001 at 6 h and 30%, P=0.009 at 24 h) and the vector control cells (36%, P=0.001 at 6 h and 18%, P=0.015 at 24 h). Similarly, overexpression of 14-3-3γ resulted in a significant increase in migration by approximately 25% (P=0.048) and 32% (P=0.002) at 24 h compared with the non-transfected and the vector control cells, respectively. For Transwell assay, the result showed that the 14-3-3γ-overexpressing cells also led to a significant increase in the invasion and migration compared with the non-transfected Cells by approximately 79% (P=0.002) and 131% (P=0.001), respectively. Our results suggested that overexpression of 14-3-3γ promotes the migration and invasion of NSCLC and it may provide new insight for treatment of NSCLC.
Ramy Elashry is an Assistant Lecturer and is pursuing his PhD in the Oral Pathology Department in Faculty of Dentistry, Mansoura University, where he has completed his Master’s degree in Basic Sciences in Dentistry in branch of Oral Pathology. He is also a Founding Committee Member of the Medical and Biological Research Center in Mansoura University. He was a Lecturer of Cancer Stem Cells Biology in multiple stem-cell training courses held in the Medical Experimental Research Center (MERC) in Faculty of Medicine, Mansoura University. Currently, he has been presented as a Co-author in two research papers in reputed international journals.
Regarding the new carcinogenesis model, cancer stem cells (CSCs) are potentially responsible for laryngeal squamous cell carcinoma (LSCC) sustained growth, metastasis and chemoradioresistance. It therefore, appears reasonable that the novel treatment approaches to LSCC should be directed against CSCs rather than tumor bulk. The current study elucidated the molecular mechanisms underpinning the cytotoxic effects of honokiol and green tea extract (Epigallocatechin-3-gallate “EGCG”) on LSCC and CSCs. The CD44high cells were immunomagnetically isolated from HEp-2 laryngeal cancer cell line, and characterized for tumorsphere formation and stem-cell genes expression through real-time qRT-PCR. Thereafter, CD44high cells were treated with either EGCG or HNK to examine their anti-proliferative and apoptosis/necrosis-inducing impacts by MTT and flow cytometry analysis respectively. Finally, the underlying mechanisms of EGCG and HNK anti-cancer effects were investigated by real-time qRT-PCR screening for genes involved in self-renewal and apoptosis. It was found that, CD44high LSCC cells were highly enriched for CSC properties. EGCG harbored a preeminent targeting potential on CD44high CSCs, mainly by apoptosis induction, while HNK conferred its Cytotoxic impacts mostly by necrosis induction with higher doses, but HNK-triggered apoptosis with lower doses was rather noticeable. EGCG outshined HNK as a potent suppressor of Notch signaling pathway. Nonetheless, HNK privileged in downregulating β-catenin and sonic hedgehog (SHH) signaling pathways. Both EGCG and HNK engaged the BCL-2 family-regulated intrinsic mitochondrial apoptotic pathway in CD44high CSCs, but EGCG induced apoptosis via caspase-dependent, p53-independent pathway, whereas HNK triggered apoptosis via caspase- and p53-dependent pathway. The caspase independent apoptotic pathway was found non-operational in LSCC treated cells.