Day 1 :
Keynote Forum
Christopher S Lange
SUNY Downstate Medical Center, Brooklyn, NY, USA
Keynote: Cancer stem cells in breast and gynecological cancers: How to individualize treatment based on the sensitivity of patient’s CSCs
Time : 09:40-10:40
Biography:
Christopher S Lange is the Associate Chair, Department of Radiation Oncology, SUNY Downstate Medical Center, Brooklyn (2010–Present), Professor of Molecular and Cell Biology, School of Graduate Studies, SUNY Downstate Medical Center (1992–Present), Professor, Director, Radiobiological Division, Department of Radiation Oncology, SUNY Downstate Medical Center (1980–Present), Associate Director, Residency Program, SUNY Downstate Medical Center (2009), Assistant Professor of Radiology, Radiation Biology and Biophysics, University of Rochester School of Medicine and Dentistry, New York (1969–1980), NHS Senior Research Officer, Christie Hospital and Holt Radium Institute, Manchester, England (1968–1969), NHS Research Officer, Christie Hospital and Holt Radium Institute, Manchester, England (1962–1968), MRC Research Assistant, Radiobiology Laboratory, Churchill Hospital, Headington, England (1961–1962).
Abstract:
A necessary and appropriate condition for cancer cure is the elimination of all of a patient’s cancer stem cells (CSCs). However, CSC identification has been problematic. Cell surface biomarkers have been claimed to select SCs and CSCs. But, only a tiny fraction of the selected cells are functionally SCs or CSCs. Hill, Kern and Shibata, show that, if based on such markers, the numbers are internally inconsistent, throwing the CSC hypothesis in doubt. Functional assays do not have this problem. Agar colonies from individual patient cervical cancers showed that inherent radiosensitivity (SF2) of the cells that formed colonies was the single most important factor correlating with clinical outcomes, but large error bars prevented accurate outcome predictions for individual patients. Our Hybrid Spheroid (HS) Assay (HSA) [US Patent No.: 8,936,938] solves this problem. HSs are composed of an initial known mixture of fibroblasts and tumor cells, forming an in vivo-like ex vivo system that provides a CSC niche. HS growth curves provide the CSC fraction, the SF for each tested agent, and clinical outcome predictions for solid tumors. The impact of our HSA is 3-fold: (1) In the cancer clinic, patients predicted to fail on the standard treatment and could be offered alternatives which are also based on the assay. (2) The selection and testing of potential new therapeutic agents in the pharmaceutical industry could use the HSA to determine which agents are valuable for further clinical testing, avoiding the considerable expenses of a negative clinical trial and considerably reducing the cost and time to bring successful agents into the clinic. (3) The HSA could also be used to determine if there is a subset of patients whose tumors are susceptible to the new modality, and hence these patients could be identified by the HSA to develop a battery of agents likely to be useful on select tumors in select patients. Each of these impacts is not currently available in the clinic or in the pharmaceutical industry. The clinical impact (1) alone should lead to major increases in cancer cure rates and the second and third impacts would magnify these increases.
Keynote Forum
Shinji Osada
Gifu Municipal Hospital, Japan
Keynote: Strategy for colorectal cancer liver metastases
Time : 10:40-11:25
Biography:
Shinji Osada is a Professor at the Department of Surgical Oncology, Gifu University School of Medicine, Japan. He has published several articles in the field of Ophthalmology. He is a recipient of many awards and grants for his valuable contributions and discoveries in major area of research. His international experience includes various programs, contributions and participation in different countries for diverse fields of study. His main research areas are Anti-Cancer Drug, Eye Cancer, Eye diseases, Cancer Immunobiology and Cancer Immunobiology.
Abstract:
In this presentation, the surgical indications for liver metastasis from colorectal cancer (CRC) and its optimal timing will be discussed. Clinically, our treatment policy has been to perform hepatectomy first, if the resection can be done with no limit on size and number of tumors. However, if curative resection is not, chemotherapy is begun first and timing for the possibility of a radical operation is planned immediately. Recurrence was detected after hepatectomy, similar between simultaneous and staged resection, but early detection was higher in simultaneous cases, indicating the staged operation to be better. As a research target focused on hepatocyte growth factor (HGF) and its receptor (c-Met), the signaling pathway might induce cancer progression in the process of liver regeneration after hepatectomy. Actually, c-Met overexpression was closely associated with liver metastases, but its expression was detected to reduce in the metastatic site compared with primary lesions. In addition, pre-treatment of CRC cells with HGF enhanced 5-FU-induced cell death by 63% compared with the control during the expression of signaling pathway by HGF/c-Met activation. E2F is a transcriptional factor of thymidylate synthase (TS), which is important to metabolite 5FU, and the D-type cyclins, which play a critical role in the cell cycle and correlate the activation of E2F. The expression of E2F1 was decreased significantly to 50.5% by HGF with a reduction of cyclin D1 to 52.1%. TS were also decreased in a time-dependent manner to 80.6±2.0% after 24 hours and to 52.7±1.5% after 96 hours. In conclusion, the presence of HGF was found to increase the 5FU-induced death signal, the best procedure for favorable patient prognosis will be a hepatectomy after chemotherapy. The present study also lead to a novel concept in which the hepatectomy-induced high serum level of HGF for liver regeneration allows drug-resistant cancer cells to become sensitive again.
Keynote Forum
Antonio Gómez-Muñoz
University of the Basque Country, Spain
Keynote: Regulation of pancreatic cancer cell migration by the axis ceramide kinase/ceramide 1 phosphate
Time : 11:45-12:30
Biography:
Antonio Gomez-Muñoz received his PhD in Biochemistry and Molecular Biology from the University of the Basque Country (Bilbao, Spain) in 1988. Part of his thesis was developed at the Medical School of the University of Nottingham in the UK during 1987. He achieved postdoctoral training at the University of Alberta (Edmonton, Alberta, Canada) from 1988 to 1994. He then accepted a Research position at the Spanish Research Council (CSIC) from 1995 to 1996. From 1997 to 1998 he worked as Researcher in the Faculty of Medicine, University of British Columbia (Vancouver, British Columbia, Canada). He then returned to the University of the Basque Country where he is currently Professor of Biochemistry and Molecular Biology. His major research interest is on the targeting of sphingolipid metabolism with the aim of developing new strategies for prevention of inflammatory diseases, obesity, and cancer. He has produced over 100 publications in the field.
Abstract:
Pancreatic cancer is an aggressive disease characterized by invasiveness, rapid progression and profound resistance to treatment. It is the fourth leading cause of cancer mortality with a 5-year survival rate of only 6%. Accumulating evidence indicates that sphingolipids play critical roles in cancer growth and dissemination. In particular, ceramide 1- phosphate (C1P), which is formed by the action of ceramide kinase on ceramide, stimulates cell proliferation (1), and promotes cell survival (2, 3). The mechanisms by which C1P stimulates cell growth involves activation of extracellularly regulated kinases 1 and 2 (ERK1/2), phosphatidylinositol 3-kinase (PI3K), c-Jun N-terminal kinase (JNK), or mammalian target of rapamycin (mTOR), whereas C1P-enhanced cell survival implicates inhibition of serine palmitoyl transferase (SPT) and acid sphingomylinase (ASMase) (4). More recently, we found that C1P enhances human pancreatic cancer cell migration and invasion potently and that this effect is completely abolished by pertussis toxin (PTX), suggesting the participation of a Gi protein-coupled receptor in this process. We also observed that human pancreatic cancer cells migrate spontaneously. However, contrary to the effect of C1P, spontaneous cell migration was insensitive to treatment with PTX (5). Investigation into the mechanisms responsible for spontaneous migration of the pancreatic cancer cells revealed that ceramide kinase (CerK) is a key enzyme in the regulation of this process. In fact, inhibition of CerK activity, or treatment with specific CerK siRNA to silence the gene encoding this kinase, potently reduced migration of the pancreatic cancer cells. By contrast, overexpression of CerK stimulated cell migration, an action that was concomitant with prolonged phosphorylation of ERK1-2 and Akt, in a PTX independent manner. It can be concluded that the axis CerK/C1P plays a critical role in pancreatic cancer cell migration/invasion, and that targeting CerK expression or activity may be a relevant factor for controlling pancreatic cancer cell dissemination.
Keynote Forum
Guilin Tang
University of Texas MD Anderson Cancer Center, USA
Keynote: Clonal cytogenetic abnormalities of undetermined significance
Time : 12:30-13:10
Biography:
Guilin Tang is a Hematopathologist and Cytogeneticist, Section Chief of Clinical Cytogenetic Laboratory in the Department of Hematopathology, and Adjunct Medical Director of the Department of School of Health Professions. Her clinical interests include diagnosis of hematologic neoplasms (both leukemia and lymphomas) and cancer cytogenetics. Her major research interest is the characterization and risk stratification of cytogenetic abnormalities in various types of hematological malignancies, to better understand the pathogenesis, identify new clinicopathologic entities and predict patient prognosis. She is also very interested in characterization of clinically indolent cytogenetic clones (clonal cytogenetic abnormalities of undetermined significance), especially those emerged following cytotoxic therapies.
Abstract:
Myelodysplastic syndromes are a group of hematopoietic stem cell diseases characterized by cytopenia(s), morphological dysplasia, and clonal hematopoiesis. In some patients, the cause of cytopenia(s) is uncertain, even after thorough clinical and laboratory evaluation. Evidence of clonal hematopoiesis has been used to support a diagnosis of myelodysplastic syndrome in this setting. In patients with cytopenia(s), the presence of clonal cytogenetic abnormalities, except for +8, del (20q) and –Y, can serve as presumptive evidence of myelodysplastic syndrome. Recent advances in next generation sequencing have detected myeloid neoplasm-related mutations in patients who do not meet the diagnostic criteria for myelodysplastic syndrome. Various terms have been adopted to describe these cases, including clonal hematopoiesis of indeterminate potential and clonal cytopenia of undetermined significance. Similarly, studies have shown that certain chromosomal abnormalities, including ones commonly detected in myelodysplastic syndrome, may not be associated necessarily with an underlying myelodysplastic syndrome. These clonal cytogenetic abnormalities of undetermined significance (CCAUS) are similar to clonal hematopoiesis of indeterminate potential and clonal cytopenia of undetermined significance. Here, we review the features of CCAUS, distinguishing CCAUS from clonal cytogenetic abnormalities associated with myelodysplastic syndrome, and the potential impact of CCAUS on patient management.
- Cancer Therapies | Radiation Oncology | Organ Specific Cancer
Location: Olimpica 1
Chair
Christopher S Lange
SUNY Downstate Medical Center, Brooklyn, NY, USA
Session Introduction
Kyungmin Shin
The University of Texas MD Anderson Cancer Center, USA
Title: Clinical indications for mammography in men and correlation with breast cancer
Time : 14:20-14:50
Biography:
Kyungmin Shin MD is an Assistant Professor at the Department of Diagnostic Radiology at the University of Texas MD Anderson Cancer Center, section of Breast Imaging. After obtaining her Diagnostic Radiology training at University of Virginia Health System and Breast Imaging Fellowship Training at Emory University, she began her academic career at Baylor College of Medicine, Houston, Texas, in 2013. In 2014, she joined University of Texas MD Anderson Cancer Center and currently practices multimodality breast imaging. She has a keen interest in clinical research, especially in tomosynthesis and breast MRI, and is actively participating in several clinical research projects.
Abstract:
Purpose: To examine presenting clinical symptoms and imaging findings and correlate them with biopsy-proven breast cancer in men.
Method & Materials: 429 male patients who presented for mammography at one institution between January 2004 and December 2014 were retrospectively evaluated. Of the 429 patients, 291 presented with clinical symptoms for diagnostic mammography and 138 presented for screening mammography. The presenting clinical symptoms in 291 patients were recorded and correlated with imaging (mammography and sonography) and histopathology findings.
Results: A total of 291 patients were included. Multiple symptoms were possible and there were a total of 318 clinical symptoms. 190 (60%) presented with palpable abnormalities, 44 (14%) with non-focal pain, 31 (10%) with swelling, 14 (4%) with breast enlargement, 13 (4%) with focal pain, 13 (4%) with other symptoms, 7 (2%) with skin changes and 6 (2%) with nipple discharge/changes. 290 patients underwent mammography and 176 patients underwent sonography. A total of 41 cancers were diagnosed, most invasive ductal carcinoma. Statistical analysis of the clinical symptoms demonstrated that nipple discharge/changes and skin changes (mostly with associated palpable abnormalities) had the highest sensitivity. Analysis of mammography findings revealed that 52 patients showed either a mass or a focal asymmetry on mammography, of which 38 (73%) were diagnosed with cancer. Only three patients (1%) who had neither a mass nor a focal asymmetry were diagnosed with cancer.
Conclusion: Correlating clinical symptoms and imaging findings can help to develop more accurate probabilities for timely and accurate diagnosis of breast cancer in men. Clinical symptoms of nipple discharge/changes, skin changes with associated palpable abnormalities and mammographic findings of masses and focal asymmetries were associated with male breast cancer. Pain, breast enlargement and swelling were unlikely to be associated with breast cancer.
Mario Dolera
The National Foundation For Veterinary Studies and Research, Italy
Title: Volumetric modulated arc (radio) therapy in pets treatment: The “La Cittadina Fondazione†experience
Time : 14:50-15:20
Biography:
Mario Dolera completed his degree in Veterinary Medicine, Specialist in Pathology and Clinical of Animal of Affection (Orthopedics), PhD Veterinary Clinical Sciences (Neurology). Head of La Cittadina Fondazione Studi e Ricerche Veterinarie Romanengo (neuroscience, imaging and radiation oncology). Author of 40 scientific publications and 14 conference communications.
Abstract:
Volumetric modulated arc (radio) therapy (VMAT) is a modern technique for cancer irradiation widely used in human radiotherapy that allows high doses to be delivered to tumor volumes and low doses to the surrounding organs at risk (OAR). Veterinary clinic managing cancers in small animals (dogs, cats, rabbits) takes a natural advantage from this feature due to the small target volumes and distances between target and the OAR. In particular, sparing the OAR permits dose escalation and hypofractionation regimens reduce the number of treatment sessions with a simpler manageability in the veterinary field. Multimodal volumes definition is mandatory for the small volumes involved and a positioning device precisely reproducible with a setup confirmation is needed before each session for avoiding target missing. Also, the treatment plan elaboration must pursuit hard constraints and objectives and its feasibility has to be evaluated with a per patient quality control. The aim of this work is to report our center results with hypo-fractionated stereotactic irradiation of neural tumors in dogs interpret to brain meningiomas and gliomas, trigeminal nerve tumors, brachial plexus tumors, onco-endocrinology in dogs related to pituitary and adrenal tumors with vascular invasion and rabbit thymomas. In comparison with literature data, VMAT as a safe and viable alternative to 3D conformal radiotherapy, cone-based stereotactic radiotherapy as well in selected cases to surgery or chemotherapy alone or as an adjuvant therapy in pets.
Hassan Chaddad
University of Strasbourg, France
Title: Combining 2D angiogenesis and 3D Osteosarcoma microtissues to improve vascularization
Time : 15:20-15:50
Biography:
Hassan Chaddad has completed his Pharmacy Degree from Lebanese International University (LIU) and his Masters in Pharmacology from USEK University in Lebanon. He is now pursuing his PhD from Strasbourg University, Faculty of Medicine (France).
Abstract:
Introduction: The number of patients suffering from cancers worldwide is increasing, and one of the most challenging issues in oncology continues to be the problem of developing active drugs economically and in a timely manner. Considering the high cost and time-consuming nature of the clinical development of oncology drugs, better pre-clinical platforms for drug screening are urgently required. So, there is need for high-throughput drug screening platforms to mimic the in vivo microenvironment. Angiogenesis is now well known for being involved in tumor progression, aggressiveness, emergence of metastases, and also resistance to cancer therapies.
Materials & Methods: In this study, to better mimic tumor angiogenesis encountered in vivo, we used 3D culture of osteosarcoma cells (MG-63) that we deposited on 2D endothelial cells (HUVEC) grown in monolayer. Combination of 2D HUVEC/3D MG-63 was characterized by indirect immunofluorescence, scanning electron microscopy, optical microscopy and mRNA expression (qPCR).
Results: We reported that endothelial cells combined with tumor cells were able to form a well-organized network, and those tubule-like structures corresponding to new vessels infiltrate tumor spheroids. These vessels presented a lumen and expressed specific markers as CD31 and collagen IV. The combination of 2D endothelial cells and 3D microtissues of tumor cells also increased expression of angiogenic factors as VEGF, CXCR4 and ICAM1.
Conclusion: The cell environment is the key point to develop tumor vascularization in vitro and to be closer to tumor encountered in vivo.
Fikri Sekcuk Simsek
Firat University, Turkey
Title: The important overlapping problem between malign and benign thyroidal nodules in cancer patients with FDG-PET/CT
Time : 16:10-16:40
Biography:
Fikri Selcuk Simsek completed his Bachelor’s, Master’s and Doctorate Degrees from EskiÅŸehir Osmangazi University, Medicine Faculty. Presently, he is working as an Assistant Professor in Nuclear Medicine Department at the Firat University. His expertise is cancer evaluation with PET/CT scanning, differentiated thyroidal carcinomas, benign thyroidal disorders, and radionuclide therapeutic approaches. He has published approximately 25 scientific articles and given oral speeches.
Abstract:
Statement of the Problem: Thyroidal nodules are often detected in patients referred for another disease called incidentaloma. The nodule frequency in autopsies is as high as 50%. Due to advances in imaging methods, the numbers of detected nodules have been increasing and this affects cancer patients, too. Widespread use of FDG-PET/CT in these patients, which provides the opportunity of full body imaging are one of the main factors of this. In patients who already have malignancy, characterization of incidentalomas is an important problem. The low FDG uptake of normal thyroid tissue suggests that PET/CT may be useful in characterizing thyroidal incidentalomas. However, increased FDG uptake in some benign conditions makes it difficult. In this study, we aimed to reveal a clinical problem that may occur if the characterization of thyroidal incidentaloma in cancer patients performed with FDG-PET/CT.
Methodology & Theoretical Orientation: FNAB/histopathology results of 16/33 patients with incidentaloma who had elevated thyroidal FDG uptake shown by FDG-PET/CT were evaluated. Five patients had histopathological evaluation, 11 had cytological evaluation and 17/33 patients didn’t have any pathological result.
Findings: 4/16 patients were diagnosed with malignancy, 3/16 non-specific atypical changes and 9/16 benign incidentaloma. SUVmax of benign nodules was between 3.22–16.94 and malignant nodules were between 3.57–12.52. When results were thoroughly analyzed, 3/9 (33%) of the benign incidentalomas had higher SUVmax than all malignant nodules (13.16, 16.83, 16.94). In addition, 7/9 (77.8%) benign nodules had higher SUVmax than malignant nodule with SUVmax 3.57.
Conclusion & Significance: There is a considerable overlap in SUVmax of thyroidal incidentalomas in cancer patients. Thus, we propose that, characterization of thyroidal nodules based on SUVmax cannot be a reliable approach.
Aye Myat Thwe
University of Dundee, UK
Title: EGF and TGFα motogenic activities are mediated by the EGF receptor: identification of the signaling pathways involved in oral cancer
Time : 16:40-17:10
Biography:
Aye Myat Thwe graduated from Myanmar with a Bachelor of Dental Surgery in 2010. After practicing as a Dentist for two years, she came to UK to study at University of Dundee. She received an MRes in Oral Cancer, and progressed into the PhD programme. She is now in the 3rd year of her PhD programme.
Abstract:
Epithelial to mesenchymal transition (EMT) is the process by which cells change shape from being tightly connected epithelial cells to more motile mesenchymal cells. EMT has been reported to facilitate cancer cell migration. Cell motility is an initial first step on the road to metastasis. Epidermal growth factor (EGFR) has been reported to be overexpressed in oral cancer and is often related with poor prognosis. Epidermal growth factor (EGF) and transforming growth factorα (TGFα) are ligands that bind to EGFR and can affect a number of different cellular processes, including cell proliferation, migration, angiogenesis and inhibition of apoptosis. We aimed to measure proliferation, migration, morphology change of HSG, AZA1, HaCaT, TYS, by cell counting, photo microscopic image capturing and scratch assay in relation with addition of growth factors at 1 ng/ml, 10 ng/ml, 50 ng/ml and 24 hrs, 48 hrs, 72 hrs. 50 ng/ml of growth factors induce cell morphology changes EMT like phenotype with finger like projection, cell scattering and increase cell migration while no reliable different in cell proliferation. These morphology changes are completely blocked by one hour pre-treatment with 5 µM gefitinib (EGFR tyrosine kinase inhibitor, 5 µM erlotinib (EGFR kinase inhibitor) and PD25 µM ( inhibitors of MEK1 and MAKP kinase) in HSG and AZA1 cell lines. The cell migration of TYS and HSG cell lines are completely blocked by one hour pre-treatment with one hour pre-treatment with 5 µM gefitinib (EGFR tyrosine kinase inhibitor, 5 µM erlotinib (EGFR kinase inhibitor) and PD25 µM (inhibitors of MEK1 and MAKP kinase).
Devashish Sengupta
Assam University, India
Title: Role of free-base and metallated porphyrin derivatives promoting apoptosis as a consequence of cancer photodynamic therapy: synthesis, characterization, and photobiological activities
Time : 17:10-17:40
Biography:
Devashish Sengupta has completed his PhD from The University of Sydney, Australia, under the supervision of Professor Peter A Lay. He is currently working as an Assistant Professor at the Department of Chemistry, Assam University, Silchar, Assam, India. His research interests include the photobiochemistry related to cancer photodynamic therapy, and antiviral activities of synthetic amphiphilic photosensitizers like fullerenes, porphyrins, porphyrin analogues, and other bioactive synthetic derivatives.
Abstract:
Structural modifications of free-base and metallated hydrophilic porphyrin macrocycles: (a) with combinations of different cationic/anionic/neutral aromatic functions at the meso-positions, (b) capable of forming nanocomposites with Fe3O4 nanoparticles, and (c) functionalized with fullerenes through linkers via electrovalent or covalent interactions are designed, synthesized, isolated and characterized. Redshifts of absorption wavelengths beyond 640 nm along with the production of high quantum yields of singlet oxygen were achieved through the mentioned modes of derivatization of porphyrins under photodynamic conditions. Upon treatment of various cancer cell lines with these photosensitizers (PSs), some of them demonstrated significant ability to upregulate cellular reactive oxygen species (singlet oxygen) along with the promotion of apoptosis. The structure-activity relationship (SAR) that evolved between the photochemistry, photophysics and photobiological activities of these derivatives is indicative of their roles as well-suited candidates for non-invasive targeted oncological photodynamic therapy (PDT). Efficient accumulation of some of these PSs into the oxygen-rich cell organelles like mitochondria, further establish their potentials as possible alternatives to the commercially used PSs to treat malignant tumors in cancer PDT.
Aurelija Vaitkuviene
Vilnius University, Lithuania
Title: Natural fluorescence for cancer diagnosis
Time : 17:40-18:10
Biography:
Aurelija Vaitkuviene PhD, MD is affiliated as a Senior Researcher at Vilnius University. She graduated from the Vilnius University, defended PhD thesis in 1984 and later trained at Wensky Laser Center in Chicago, Northwestern University (USA), at Lund University (Sweden). She is a Founding Member of the International Academy for Laser Medicine and Surgery (Florence, Italy), Past President of International Society for Laser Surgery and Medicine, and was a President of the International Phototherapy Association (IPTA), served Vilnius University as a Representative for European Cervical Cancer Association (ECCA). She has published more than 40 papers in scientific journals.
Abstract:
Digitalization of human body samples evaluation fits to personalized medicine requirements by person’s and sample data use in diagnostic algorithm. Fluorescence spectroscopy techniques are under intense introduction into the smart applications for everyday life. Cancer was one of the target areas. Endometrial pathology was an area where chemical dynamics of changes in the tissues was well recognized. Endometrial tissue samples, also endometrial washing were tested by fluorescence spectroscopy to create diagnostic algorithms, based on pathology standards. Both endometrial objects were successfully classified for benign vs. malignant condition recognition with proper accuracy. For cervical cancer prevention, both in vivo and in vitro fluorescence diagnostics devices and programs were created by local and international resources. While imaging technologies manifested as far-off practical application, the cervical smear spectroscopy was revealed to be reasonable for, at point of care application. The special diagnostic program creation for smear discrimination resulted in automatization of diagnostics, which further could be applied for data clouding and application in remote regions by health care personnels. The so called “optical biopsy” technology is the example of space science landing on the human utility level, where pure molecular information is classified by “golden standard” of pathology means. So medical experience transfer into modern technology results in the expansion of highest standards application globally.