Day 1 :
Keynote Forum
Geert C. Mudde
PhD in Immunology
Keynote: Next Generation Immuno-Therapy: OQR200 a therapeutic breast cancer vaccine with HER2/neu Specific Control of Immune Checkpoints
Time : 09:20-10:00
Biography:
Geert C Mudde received a PhD in Immunology from the University of Utrecht in 1985 and started his international professional career at the Swiss Institute for Asthma and Allergy Research in Davos. In 1992, he joined the pharmaceutical/biotech industry, where he held several senior management positions at the Novartis Research Institute in Vienna, Austria, the Parke Davis Research Institute in Fresnes, France, Ingenium Pharmaceuticals, Martinsried, Germany and at Igeneon AG, Vienna, Austria. Finally, in 2006, while joining Baxter BioScience in Vienna as interim manager. He Co-Founded the Biotech company F-Star Biotechnology, where he served as Chief Scientific Officer from 2007 to 2009. In 2009, together with Christ of Langer, he started to develop the S-TIR™ technology platform for human specific therapeutic vaccines which led to the foundation of S-TARget therapeutics GmbH in 2010. Since then he serves as CSO and Managing Director for S-TARget therapeutics as well as for the S-TIR™ technology spin-off companies OncoQR ML GmbH and TYG oncology Ltd., which were both founded in 2013.
Abstract:
Using the S-TIR™ technology platform for human specific therapeutic vaccines OncoQR ML has developed two prototype vaccines for treatment of pancreatic cancer (TYG100) and breast cancer (OQR200). Vaccines derived from this platform consist of two modules, the disease specific module, immunogen and the generic module, war head which directs the vaccines to CD32 on antigen presenting cells, especially pDCs and B cells. The immunogen in oncology is a tumour associated auto-antigen against which under normal conditions no clinically relevant immune responses can be induced. We will present conclusive proof that it is finally possible to overcome all the tricks of cancer cells to prevent therapeutic immune responses. No more need for bulk infusion of very expensive and artificial treatments such as CAR T cells or use of monoclonal antibodies, which either try to mimic tumour specific B cell responses (e.g. Herceptin and Perjeta) or try to activate cytotoxic T cells, that by chance may also kill tumours (e.g., Opdivo, Yervoy, Keytruda). S-TIR™ vaccines fully activate both arms of the patient’s own immune system resulting in tumour specific polyclonal IgG responses simultaneously with the generation and activation of tumour specific cytotoxic T cells. The responses are reversible and boostable thus allowing fine-tuning of the clinical responses on a patient to patient basis. S-TIR™ vaccines in contrast to the current check point inhibitors do not induce autoimmune disease and are tumours specific.
Keynote Forum
Kim O’Neill
PhD at the University of Ulster in the Biomedical Sciences Research Center
Keynote: Developing MOTO-CARâ„¢ to Treat Breast Cancer?
Time : 10:00-10:40
Biography:
Kim O’Neill completed his PhD at the University of Ulster in the Biomedical Sciences Research Center. He was recruited to Brigham Young University, in Provo Utah in 1992. He has published over 140 peer reviewed papers and presented his research at numerous international meetings. He is a member of the American Association for Cancer Research (AACR) and currently serves on the AACR Science Education committee.
Abstract:
Recent clinical trials using chimeric antigen receptors (CAR) T cells have demonstrated tremendous success in eradicating hematologic malignancies targeting CD19. Despite these results, how to translate this success to solid malignancies remains elusive. It is well documented that the vast majority of cancers, particularly the most common such as breast, colon and lung, fail to respond effectively to infusions of CAR T cells. The immunosuppressive tumor microenvironment, the physical barriers of solid malignancies and the unfavorable conditions for T cells at the tumor site make it a difficult challenge for CAR T cells. Moreover, CAR T cells for solid malignancies have also been hampered by expression of the tumor target on normal tissues. Macrophages, the most plastic cells of the haematopoietic system are found in all tissues and show great functional diversity. Two major macrophage phenotypes have been proposed: M1 and M2. M1 macrophages or classically activated macrophages play an important role in the recognition and destruction of cancer cells and are correlated with a more favorable prognosis. Macrophage recruitment to the tumor site is a well-documented event, it has been suggested that in aggressive breast cancer over 50% of the tumor mass is made up of macrophages. Thus, we propose the use of macrophage CARs (MOTO-CARsÔ) as a better approach for the treatment of solid malignancies, particularly breast cancer. Our research takes advantage of the innate ability of macrophages to penetrate tumors and of their tumoricidal abilities. We have genetically engineered the cytosolic signaling domain of the toll-like receptor 4 (TLR-4) and fused it to an extracellular domain single chain variable fragment (scFv) against novel tumor targets discovered in our lab in addition to scFvs against other targets used for CAR therapy. Preliminary results are showing promise and suggest MOTO-CARs may be a major player in driving the success of immunotherapy for breast cancer forward.
Keynote Forum
Rufus Mark
graduated from Yale University
Keynote: Five day accelerated partial breast irradiation (APBI) using stereotactic body radiation therapy (SBRT) in stage 0-ii breast cancer
Time : 11:00-11:40
Biography:
Abstract:
Randomized trials in selected early stage breast cancer patients with upto 10 year follow-up have proven that accelerated partial breast irradiation (APBI) given via high dose rate (HDR) implant bid in five days is equivalent to whole breast external radiation therapy (XRT) given QD in 5-6 weeks in regard to breast tumor local recurrence (LR). However, complications with APBI implant in a medicare database review have been significant with 3.95% of women requiring mastectomy, 16.2% developing infections and another 16.3% experiencing non-infection complications including rib fractures, fat necrosis and breast pain. Recently, APBI using non-invasive intensity modulated radiation therapy (IMRT) or stereotactic body radiation therapy (SBRT) given QD in five fractions has been shown in another randomized trial with five year follow-up to be equivalent to QD XRT in 6 weeks, with respect to LR. IMRT/SBRT was superior in regard to acute effects, late effects and cosmesis.
- Screening, Detecting and Diagnosing Breast Cancer | Breast Cancer Therpy, Prevention and Medicine | Case Studies
Chair
Geert C. Mudde
OncoQR ML GmbH, Austria
Co-Chair
Cristian Scatena
University of Pisa, Italy
Session Introduction
Pascale A. Cohen
Faculty of Pharmacy at University of Lyon
Title: The ZNF217 oncogene is a crucial mediator and indicator of the bone metastatic process in breast cancer
Time : 11:40-12:10
Biography:
Pascale A Cohen is a Full Professor in Molecular Biology and Biotechnology in the Faculty of Pharmacy at University of Lyon, France since 2005. She is also a Principal Investigator and manages a team in the CRCL Cancer Research Center of Lyon, France. She got a Degree in Pharmacy, a PhD in Biomedical Sciences. She was a Postdoctoral fellow in the Cancer Research Campaign Laboratories, University of Dundee, Scotland, U.K. She got several honors such as exceptional class professor distinction and her research work has been awarded by many prizes. She is also committed in several national and international education programs and is frequently requested as external scientific referee for international scientific journals or committees. She has been recently awarded a full bright grant to develop à scientific program at the Albert Einstein College of Medicine, NY, USA.
Abstract:
Newly discovered molecular functions of ZNF217 indicate that it orchestrates complex intracellular circuits as a new key regulator of tumorigenesis. This talk will focus on recent research on ZNF217 driven molecular functions in human breast cancers, revisiting major hallmarks of cancer and highlighting the downstream molecular targets and signaling pathways of ZNF217. Among the ZNF217 driven mechanisms which lead to aggressiveness and metastasis in breast cancer our group discovered that the ZNF217 oncogene is a crucial mediator and indicator of the bone metastatic process. Indeed, patients possessing high ZNF217 m-RNA expression levels in primary breast tumors had a significantly higher risk of developing bone metastases. ZNF217 stably transfected MDA-MB-231 breast cancer cells (MDA-MB-231-ZNF217) displayed the dysregulated expression of a set of genes with bone homing/bone metastasis characteristics, which clearly overlapped with two previously described osteolytic bone metastasis gene signatures and also newly highlighted the bone morphogenetic protein (BMP) pathway. This latter was activated in MDA-MB-231-ZNF217 cells and its silencing by several inhibitors was sufficient to rescue ZNF217 dependent cell migration, cell invasion or chemotaxis towards the bone environment. Finally, using in vivo non-invasive multimodal imaging, we found that ZNF217 increases the metastatic growth rate in the bone and accelerates the development of severe osteolytic lesions. Altogether, this study highlights that in breast cancer, ZNF217 is a new indicator for the emergence of bone metastasis and that future therapies targeting ZNF217 and/or of the BMP signaling pathway may be beneficial for patients by preventing the development of bone metastasis.
Cristian Scatena
Assistant Professor of Pathology at the Department of Translational Research and of New Surgical and Medical Technologies of the University of Pisa (Italy)
Title: Targeting Breast Cancer Stem Cells with FDA approved antibiotics
Time : 12:10-12:40
Biography:
Cristian Scatena is junior Assistant Professor of Pathology at the Department of Translational Research and of New Surgical and Medical Technologies of the University of Pisa (Italy). He is an MD PhD with specialization in Surgical Pathology. He is a consultant histopathologist at the Division of Pathology I at Pisa University Hospital (Italy). He has published more than 25 papers in peer-reviewed journals and has been serving as Associate Editor for the journals Cancer Cell International and Frontiers in Oncology.
Abstract:
Cancer stem cells (CSCs) have been implicated in disease recurrence, metastatic spread and poor patient survival in multiple tumor types, breast cancer included. Under anchorage-independent growth conditions, CSCs spontaneously form 3D-spheroid structures, known as tumorspheres. Key mitochondrial-related enzymes involved in beta-oxidation and ketone metabolism are selectively over-expressed in tumorspheres as well as proteins involved in mitochondrial biogenesis. Inhibition of mitochondrial function effectively reduces tumorspheres formation, representing a new potential approach for eradication of CSCs in breast cancer patients. Because mitochondria evolved from bacteria, many classes of FDA-approved antibiotics actually target mitochondria, as a mild side-effect. In vitro and in vivo evidence supports a potential inhibitory effect on cancer growth of doxycycline, a derivate of the antibiotic tetracycline.
Workinesh Daba Seboka
Addis Ababa University, Ethiopia
Title: Coping strategies of women with breast cancer seeking care at Black Lion Hospital department of oncology, Addis Ababa, Ethiopia
Time : 12:40-13:10
Biography:
Workinesh Daba Seboka has Masters of Public Health in Reproductive and Family health, BSc in midwifery and BA in management from 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 teaching and Clinical work experience as an expert midwife professional and public health professional.
Abstract:
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 Epi-Data3.1 after which it was exported to SPSS version 23 for analysis.
Darlaine Honey
Patient Advocate, UK
Title: What about Invasive Lobular Breast Cancer?
Time : 14.00-14.30
Biography:
Darlaine Honey is a 57 year old Sexual Health Advisor for the NHS. Studied Psychology 2009 - 2012 at London Southbank University. Diagnosed with Invasive lobular carcinoma 2016 she fought for a double mastectomy after 4 margins, and a salpingo oopherectomy which showed a STIL lesion of the fallopian tube. She is ER/PR positive, HER negative, BRACA negative. Troubled by the lack of follow up diagnostics for this unique subtype, it is her passion to raise awareness of the need for more sophisticated follow up due to the nature and metastatic pattern of invasive lobular breast cancer. Feisty and dedicated to improving diagnosis, care and ongoing research into Invasive Lobular breast cancer and quality of life for women experiencing the many side effects of post operative medications such as AI's and Tamoxifen which for many is the cause of discontinuing medication. Often, certain brands of medication are refused at GP level due to cost, but these are often the meds with the least side effects. Treatment length is a factor in decision making as women battle some quite severe side effects. There is also the failure of some of these treatments to consider. Darlaine Honey is an advocate raising awareness and improving the lives of women after breast cancer with a special interest in sex after breast cancer.
Abstract:
Ductal breast cancer is the most common in the US (26%) while lobular cancer takes sixth position i.e., 6%. This unique subtype is often not seen on imaging, especially in dense breast tissue. This unique subtype is a single cell formation, often seen as a reaching branch like pattern and equally as hard to get a clear margin. It is often bilateral if not at diagnosis, within a few years afterwards. It does not always form a mass therefore difficult to detect on manual examination. Initially, this type was thought to have a good prognosis but is often found to have secondary's within five to ten years. Author proposed that this is possibly because the formation of the cancer may have already left the primary site before it is found and too small to pick up on lymph node removal as it has already travelled to another site; bones, GI tract or peritoneal cavity in the case of lobular metastatic pattern where is sits undetected. I propose a lymph node wash, similar to a peritoneal wash which may help to decide whether this is indeed the case. [Q1] I would also like for this unique subtype to be more researched and reflected in the patient leaflets which do not represent the true picture of invasive lobular cancer. In the case of lobular carcinoma in situ, it would be impossible to ascertain exactly when the change from in situ becomes invasive due to the nature of this unique subtype. It would be unfair to ignore a patient's wishes to have both breast removed to alleviate the severe anxiety of enduring an annual diagnostic mammogram knowing that the cancer may not be visible on imaging.
Ngozi Ejedimu
The Judah Foundation for Breast Cancer, Nigeria
Title: Surviving Breast Cancer in Nigeria
Time : 14:30-15:00
Biography:
Ngozi Ejedimu is a lawyer turned breast cancer advocate living in Nigeria. She is an entreprenuer who turned her juicing habits during treatment into a business she currently runs along with Whatcancernaija under the registered body known as “THE JUDAH FOUNDATION FOR BREAST CANCER”. She was diagnosed of breast cancer in 2016 and now cancer free. She strongly encourages women to soar after breast cancer and adhere to an after care plan.
The long term goal of the Foundation is to establish breast cancer centers in Nigeria through partnership with healthcare workers and organisations globally in the area of funding and expertise.
Abstract:
Although Breast Cancer awareness in Nigeria has improved tremedously over the years, a lot needs to be done in terms of the seriousness it deserves as people have died and are still dying from the disease. There is a dearth of information on life after breast cancer in terms of survivorship as focus is always more on treatment and surgery.
This study is based on data from a breast cancer support group as well as information gotten from social media via instagram.
Materials and Methods: Case studies based on treatment and surgical methods available to each woman as well as opinions on how journey starts and progresses. This is within an 18 Months period.
Workinesh Daba Seboka
Addis Ababa University, Ethiopia
Title: Assessment of knowledge, attitude and practices on breast cancer and breast self examination among female students, school of medicine and health science, Ambo University, Oromiya region, Ethiopia
Time : 15:00-15:30
Biography:
Workinesh Daba Seboka has Masters of Public Health in Reproductive and Family health, BSc in midwifery and BA in management from 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 teaching and Clinical work experience as an expert midwife professional and public health professional.
Abstract:
In Ethiopia, breast cancer is the most common cause of cancer-related mortality and morbidity. Level of knowledge, attitude and practices of female university students about breast cancer and breast self-examination is not thoroughly examined. To assess the knowledge, attitude and practices on breast cancer and breast self- examination of female students of the school of medicine and health science, Ambo University, 2017
Pascale Cohen
Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY
Title: ZnFX Oncogene’s C-terminus regulates cell proliferation and genomic binding dynamics in breast cancer cells
Biography:
University of Lyon, The Cancer Research Center of Lyon, France
Abstract:
ZnFX (Zinc Finger Protein) is an oncogenic transcription factor that induces Epithelial Mesenchymal Transition, increased invasive properties and resistance to chemotherapy. ZnFX is known to repress or activate genes involved in survival pathway and cell proliferation. We aimed to investigate the effect of ZnFX’s C-terminus on cell proliferation and genomic DNA binding. ZnFX was knocked-out in MDA-MB231 (breast cancer cells) cells to yield Cl73 cells (Cl73-ΔZnFX). The Cl73-ΔZnFX cells were stably transfected with ZnFX WT, ZnFX Δ1014-1048 or ZnFX Δ747-1048 isoforms. We found that the knocking-out ZnFX reduces proliferation of MDA-MB231 cells. Re-expression of ZnFX WT or ZnFX Δ1014-1048 enhances proliferation of Cl73-ΔZnFX cells, while ZnFX Δ747-1048 did not have an impact on Cl73 proliferation. Thus, we deduced that the absence of ZnFX or the 301 amino-acid truncation in its C-terminus decreased proliferation of MDA-MB231. This suggests that the ZnFX’s c-terminus may positively regulate cell proliferation. To better determine how truncation of ZnFX affects its genomic binding dynamics, we performed Single Particle Tracking Microscopy. We found that the ZnFX Δ747-1048 isoform resides on chromatin for significantly shorter time periods relative to ZnFX WT and ZnFX Δ1014-1048 isoform. We thus deduced that the 301 amino-acid (aa) sequence (possessing the transcriptional repressor domain) lacking in the Δ747-1048 isoform is crucial for genomic binding. These preliminary data suggest that deregulated ZnFX‘s DNA-binding behavior, driven by its 301 aa C-terminus sequence, is paired with defect in stimulating cell proliferation
Petra El Hajj
Lebanese University, Lebanon
Title: Evaluation of androgen receptor expression by immunohistochemistry in breast cancer tissues from Lebanese patients
Biography:
El Hajj Petra has completed his PhD from Lebanese University and Universite Libre de Bruxelles, where she has published four articles on TYRP1 expression and regulation in melanoma, among them two in the “British Journal of Cancer”. Now-a-days, she is a Lecturer at Lebanese University, Faculty Of Sciences and a Researcher in the same institution in the field of triple negative breast cancer in female Lebanese patients.
Abstract:
The most aggressive type of breast cancer is the triple negative breast cancer (TNBC) due to its lack of hormone receptors, HER2 amplification and targeted therapy. Recent studies have demonstrated the implication of androgen receptor (AR) in prognosis and therapy of TNBC although this has not yet been completely elucidated. The current work aimed at determining the retrospective study in Lebanese TNBC patients, the expression of AR in 78 TNBC tissues by immunohistochemical examination and correlating its expression with clinico-pathological parameters. Bivariate analyses showed an interesting inverse correlation between AR expression and tumor size (p=0.004), mitotic score (0.02) and a positive association of AR with patients’ age at diagnosis (p=0.03), suggesting anti-proliferative role in TNBC. Moreover, tumor size showed a positive correlation with mitotic score but showed no association with tumor grade, lympho-vascular invasion or histologic type. A positive correlation was seen between tumor grade and mitotic score. In vitro studies are ongoing to assess growth and to determine signaling pathways in the androgen AR proliferation axis at RNA and protein levels.
Manal Almalky
King Saud university Riyadh, Saudi Arabia
Title: The synergistic effect of melatonin and vitamin D3 on the gene expression of Bcl-2 and Bax in MCF-7 breast cancer cell line
Biography:
Manal Mohammad Al Malki is a Masters student at King Saud University. She has undertaken this research project under the supervision of well known Dr.Samina Hyder Haq. Her studies are of great value and importance for the scientific community as her conclusive molecular biology experements revealed a direct relationship of the gene expression of Bcl-2/Bax ratio in the etiology of breast cancer and possibility of using melatonin and vitamin D3 along with Tamoxifen which could greatly increase the efficacy and better strategy to treat breast cancer.
Abstract:
There is now compelling evidence by epidemiology and experimental studies that disruption of circadian rhythm and decreased melatonin synthesis is a risk factor for the breast cancer. Also interestingly there is a strong co-relationship between the night shift work and the incidence of breast cancers. Animal model of cancer suggests that the disruption of light and night (LAN) disrupts the secretion of melatonin and enhances the growth of chemical induced mammary adenocarcinoma in comparison with the control animals. The use of melatonin along with tamoxifen greatly increase the efficacy of the drug as well as better strategy to treat breast cancers, which are now used in some clinical studies. Similarly, the use of melatonin and vitamin D3 has shown to inhibit breast cancer growth and promote apoptosis. With the ever increasing rate of breast cancer incidences there is a strong need to look at the alternative drugs and treatment strategy for the treatment of breast cancer. There is also a need for the better understanding of how these drugs may affect the tumour cell apoptosis and control of metastasis. Our in-vitro results with breast cancer cell line MCF-7 showed that the synergistic treatment of vitamin D3 and melatonin can upregulate pro-apoptotic Bax gene expression as well as protein expression as shown by RTPCR and immunoblotting techniques and at the same time downregulating the gene expression and protein expression of anti-apoptotic gene BCl-2. BCL-2/Bax ratio usually determines the extent to which apoptosis is induced or suppressed. Our gene expression and immunoblotting data supports the notion that melatonin and vitamin D3 susceptible apoptosis is induced by significantly suppressing BCL-2 expression with concombitant upregulation of Bax gene expression and protein expression.
Nora Alkeraishan
King Saud university Riyadh, Saudi Arabia
Title: The effect of melatonin and Vitamin D3 on the gene expression of P53 in MCF-7 breast cancer cell line
Biography:
Nora Saad Alkeraishan is a Masters Student at King Saud University, Riyadh, Saudi Arabia. She undertook this research project under direct supervision of well known scientist Dr. Samina Hyder Haq. Her interesting studies on the effect of melatonin and vitamin D3 on breast cancer cell line MCF-7 revealed that melatonin could significantly upregulate p53 gene expression in cultured cells and observed no direct relatioship of vitamin D3 in upregulating p53 gene expression. Currently, she is involved in genotyping the p53 to detect mutations present in the gene itself.
Abstract:
P53 was identified as first tumor suppressor gene which is actively involved in numerous cellular mechanisms such as initiating DNA repair mechanisms, apoptosis and cell cycle arrest. More than 50% of all human cancers have a mutated non-functional p53 expression. Breast cancer (BC) is one of the leading cause of mortality in females and mutated p53 is documented to be the causitive agent in only 20% of them. However, mutation in p53 in BC results in more aggresive form of cancer which is more resistant to the conventional therapies. Recently, multiple clinical trials suggested that the combined use of melatonin and vitamin D3 can slow down the growth of breast cancer cells. The genetic and molecular mechanisms through which these compounds initiate the cancerous cells to apoptosis or cell cycle arrest is still not fully understood. This study aims to investigate the effect of melatonin, vitamin D3 and their combined treatment on the proliferation of breast cancer cell line MCF-7 by MTT assay. Our results showed that melatonin, vitamin D3 and combined effect of vitamin D3+ melatonin inhibit proliferation of these cells by upregulating gene and protein expression of p53.