29^th Euro-Global Summit on Cancer Therapy & Radiation Oncology 2018-09-15 Rome, Italy

Biography:

Shraga Shany is a Faculty Member at the Department of Clinical Biochemistry and Pharmacology at the Faculty of Health Sciences in Ben-Gurion University of the Negev, Beer Sheva, Israel. His main research interest is in the field of vitamin D. His studies and publications include the topics of vitamin D status and metabolism in uremia, in rickets, in fracture healing and in the elderly, as well as the auto/paracrine mode of action of 1, 25-dihydroxyvitamin D in inflammatory cells. Recently, his studies are concentrated on the anti-carcinogenic activities of the active metabolite vitamin D, and its analogs, alone, and in combination with other drugs and radiotherapy. He has more than 140 peer reviewed publications with more than 3000 citations. He is teaching Clinical and Basic Biochemistry in the School of Medicine at Ben-Gurion University.

Abstract:

Ionizing radiotherapy (IR) is known to be an effective treatment of prostate cancer, as well as for other types of cancer. However, this treatment causes many severe side effects. On the other hand, recent studies demonstrate the anti-carcinogenic activity of the active metabolite of vitamin D, namely 1, 25 dihydroxyvitamin D3 (1, 25(OH)2D3). The aim of this study was to try to develop cancer–sensitizing pretreatments that may potentiate the therapeutic effect of IR. Such achievement will allow the use of lower radiation doses and limit its side effects. Toward this aim, we have incubated in vitro prostate cancer cells treatment with 1, 25(OH)2D3 alone, or with combination with other anti-carcinogenic drugs, such as sodium valporate (VPA) before IR. The results show that while IR alone (4Gy) of DU145 line of prostate cancer cells decreased cell proliferation by 30.6%, IR after pretreatment with 100nM 1, 25(OH)2D3 and 1 mM VPA, efficiently suppressed cell proliferation by 87.9% (p<0.0001). At the same time the combined pretreatment increased the DNA double-strand breaks by 58.1%, as compared to 11.8% in radiated cells without the pretreatment (p<0.002). The combined pretreatment enhanced IR induced cell cycle s-phase arrest and cell apoptotic death. The results support our highly efficient in increasing the effect of the anti-carcinogenic activity of IR. Usage of such pretreatment would increase the therapeutic effect of IR and may allow the use of lower doses of IR with less severe side effects.

Biography:

Howon Seo is pursuing an Integrated Master’s and Doctoral Degree program at Korea Advanced Institute of Science and Technology in South Korea. He completed his Bachelor’s Degree in Biochemistry and has worked in intravital imaging of circulating tumor cells with high-speed confocal microscopy. He is interested in the study of cancer metastasis and metastatic cancer therapy.

Abstract:

The circulating tumor cells (CTCs) have been considered as a seed for cancer metastasis and the level of CTCs in metastatic cancer patients has been considered as a valuable indicator for predicting the grade of cancer metastasis, efficacy evaluation of anti-cancer therapy, and potential early diagnosis of cancer recurrence. Currently, ex vivo isolation of CTCs based from a peripheral blood sample has been a major strategy for the quantitation of CTCs. However, accurate quantitation of rare CTCs, as few as 1~2 cells per ml of blood sample in patients with metastatic cancer, is technically challenging and suffers extremely low sensitivity. These limitations can be overcome by using intravital flow cytometry which provides direct detection and quantitation of circulating cells in blood flow. For direct observation of fast-flowing cancer cells in the bloodstream, a custom-built high-speed video-rate laser-scanning confocal microscope system was implemented. After the intravenous injection of cancer cells and long circulating reference cells such as red blood cells (RBCs), a dynamically changing number of circulating cancer cells and RBCs was continuously monitored by real-time imaging. By extracting the calibration factor from hemocytometric imaging analyses with intravenously injected RBCs, we could estimate the level of intravenous injected CTCs in the whole blood of a mouse. To evaluate the degrees of cancer metastases with in vivo CTC-quantitation approach, an orthotopic tumor mouse model was used. The dynamic change of metastatic CTC-level was observed during a few hours and the longtitudinal change of metastatic CTC was monitored in a single mouse, in vivo.

Biography:

Ning Deng has his expertise in antibody drug and tumor polypeptide vaccine around tumor angiogenesis inhibition. He has established antibody design and construction system, included the phage antibody library, affinity maturation and improvement based on antibody structural simulation, evaluation system for tumor peptide vaccine. He also researched on the mechanism of tumor angiogenesis in ovarian cancer and stem cell evaluation.

Abstract:

Angiogenesis plays a critical role in tumor growth. Fibroblast growth factor-2 (FGF-2) is one of the most important angiogenic factors. The over-expression of bFGF plays a crucial role to promote tumor growth, progression and metastasis. Neutralizing antibodies against FGF-2 may suppress the growth of tumor cells by blocking the FGF-2 signaling pathway. In our lab, we scanned human anti-bFGF antibody from the phage antibody library. The results showed that the human anti-bFGF antibody could significantly inhibit the tumor angiogenesis and inhibit the tumor growth and migration. Based on this antibody, a newly small molecular antibody of disulfide-stabilized diabody (ds-Diabody) against bFGF was constructed by site-directed mutation and overlap extension PCR (SOE-PCR) at the position of VH44 and VL100 in the scFv. The ds-Diabody was expressed in Pichia pastoris system. We found that the ds-Diabody against bFGF could maintain good antigen binding activity and stability in vitro and in vivo. The ds-Diabody against bFGF could efficiently suppress the proliferation, migration and invasion of human lung cancer (A549 cells) and breast cancer (MCF-7 cells), inhibit bFGF-induced activation of downstream signaling regulators, phospho-Akt and phospho- MAPK. In the nude mouse xenograft model, the ds-Diabody against bFGF could significantly inhibit tumor growth, tumor angiogenesis and lymphangiogenesis. The ds-Diabody against bFGF showed stability in vivo and could more effectively suppress the tumor growth through blockade of bFGF signaling pathway and inhibition of tumor angiogenesis, which may make it a potential therapeutic candidate antibody drug for human lung cancer therapy.

Biography:

Statement of the Problem: In most of breast cancer cells, HER2 receptors are known to be cleaved by an ectodomain sheddase, ADAM10, to liberate HER2 extracellular domain (ECD). This provides ligand-independent growth to breast cancer cells and trastuzumab, anti-HER2 agent, cannot inactivate HER2 by binding ECD portion of it. In our previous studies, we found that miR-122-5p, miRNA targeting ADAM10, and trastuzumab combinatorial administration to HER2-positive breast cancer cell line, SKBR3, increases the efficiency of trastuzumab by leading SKBR3 cells to apoptosis more through blocking the sheddase activity of ADAM10 on HER2. The aim of this study is to display that miR-122-5p, together with trastuzumab, leads SKBR3 cells apoptosis by which pathway: intrinsic or extrinsic.

Methodology & Theoretical Orientation: SKBR3 cells were first transfected with the miR-122-5p mimic for 48 hours. Then, 0.5 μM trastuzumab was applied to miR-122-5p-transfected SKBR3 cells and non-transfected SKBR3 cells for 24 hours. Next, the expression levels of CASP3, CASP8 and CASP9 genes, which are key molecules in apoptotic pathway, were examined by real-time PCR.

Findings: Expression levels of CASP3 and CASP8, but not CASP9, increased significantly in miR-122-5p-transfected Trastuzumab-administered SKBR3 cells when compared to non-miR-122-5p transfected Trastuzumab-administered SKBR3 cells. A significant increase in the expression level of CASP8 with CASP3 showed apoptosis to be activated via extrinsic pathway (instead of the mitochondrial intrinsic pathway regulated by CASP9) with the effect of miR-122-5p in trastuzumab-administered SKBR3 cells.

Conclusion & Significance: Consequently, the apoptosis enhancing effect of trastuzumab and miR-122-5p combinatorial administration through extrinsic pathway may be presented as a new treatment option for HER2+ breast cancer.

Abstract:

Sercan Ergun is working as Teaching Assistant in Ordu University and is about to finish his PhD in Department of Medical Biology and Genetics of Ondokuz Mayıs University. He was included as Researcher in a team studying briefly epigenetic changes in disease mechanisms of different types of cancers, including oncogenic/tumor suppressor gene and miRNA expression level changes, cell death mechanism analysis, development of some cancer therapy agents’ efficiencies via miRNAs. Now, he is part of a team studying in silico miRNA and ceRNA analysis, miRNA heterogenetiy, piRNA expression changes in different cancer types, especially urological cancers. He has many published many articles related to these studies. He and his team have conducted many studies on different diseases other than cancer, like Glanzmann's thrombasthenia, hemophagocytic lymphohistiocytosis, immune thrombocytopenic purpura, familial mediterranean fever, βeta (β)-thalassemia, secondary hyperparathyroidism and he has many other articles on them.

Biography:

Ewa L Gregoraszczuk specializes in Reproductive Endocrinology as well as Hormone Dependent Cancer. She graduated from the Jagiellonian University in Krakow, Poland. From 1998, she has been the Professor of Endocrinology, Head of Department of Physiology and Toxicology of Reproduction. She has authored 173 peer-reviewed articles in leading journals such as Biology of Reproduction, Reproduction, Reproductive Toxicology, Toxicology, Cancer Chemotherapy and Pharmacology. She is a Member of the Polish Endocrinology Society, International Society of Endocrinology (ISE), The New York Academy of Sciences, and The European Tissue Culture Society. She has been a Promoter for 60 MD, 16 PhD and 3 Habilitations. Her research topics are focused on the effects of metabolic hormones produced by adipose tissue in light of the increasing incidence of obesity and related problems in reproduction and hormone dependent cancer; reprotox and canceriogenic action of endocrine disruptors, testing antiepileptic drugs as a potent anticancer in combination with chemotherapy; testing leptin receptor blockers as a novel treatment for ovarian cancer.

Abstract:

Biography:

Ibrahim Khalifeh After earning his MD from Damascus Medical School in 1999, completed a surgery internship (2000-2001) and pathology residency (2001-2002) at American University of Beirut Medical Center. In 2002, he left for the USA where he did four years of training in Pathology and Laboratory Medicine at Wayne State University in Detroit (2002-2006), Oncologic Pathology and Cytopathology fellowships at MD Anderson Cancer Center (2006-2008) then he joined the University of Alabama where he completed one year of fellowship in Dermatopathology (2008-2009). Dr. Khalifeh is a diplomat of the American Board of Anatomic and Clinical Pathology, Cytopathology and Dermatopathology. He joined the Department of Pathology and Laboratory medicine at AUBMC in 2009 as assistant professor. He has been involved in multiple projects related to cutaneous leishmania, melanoma, dysplastic nevi and BRAF.

Abstract:

Background: Selective oral BRAF inhibitors show promising results in the treatment of metastatic melanomas. Consequently, this mandates checking the concordance of BRAF status in primary (PM) and metastatic (MM) melanomas to optimize individual targeted therapy.

Design: Extended BRAF testing for 9 mutations on 95 lesions from 40 patients (men/women: 27/13; age= 59 13 years) including 40 PM with their corresponding MM (n=42), recurrences (n=9) and second primaries (n=4) was performed. Multiple metastatic sites were present in 9 patients [2 sites (n=6), 3 sites (n=2) and 4 sites (n=1)].

Results: BRAF mutation status was obtained for 85/95 (89.5%) lesions. V600E was the only identified mutation type documented in 35.4% of PM vs. 18.9% of MM. The overall PM-MM BRAF status discordance rate was 32.3% (11/34), and this was significantly more frequent in PM with mutant BRAF (8/12; 67%) versus PM with wild-type BRAF (3/22; 14%, p=0.005) Patients with metastasis to lymph nodes (3/20; 15%) were less likely to be discordant compared to those with metastasis to other sites (8/14; 57.1%, p=0.023). Females (7/13; 53.8%) were more likely to have discordant PM-MM BRAF status than males (4/21; 19%, p=0.06). Patient age was similar in patients with concordant and discordant BRAF status (58 13 vs. 62 14 years; p=0.41). PM anatomic location (p=0.23) and time-to-metastasis (p=0.55) were also unrelated to PM-MM BRAF mutation discordance. Discordant BRAF mutation status was predicted by multivariate binary logistic regression: 1) the presence of a mutant BRAF in PM [OR (95% C.I.) = 23.4 (2.4-229.7)] and 2) male gender [OR = 0.094 (0.01-0.93)]. MM-MM BRAF concordance was available for 6 possible comparisons and displayed a 100% concordance rate.

Conclusion: A high discordant rate implies the need for re-testing of the MM before initiation of BRAF targeted therapy. High MM-MM concordance advocates that testing the most accessible metastatic site is sufficient to obtain accurate BRAF mutation status.

Biography:

Takeshi Motohara is Assistant Professor in Department of Obstetrics and Gynecology, Kumamoto University, Japan. He is now engaged in research on molecular biology of ovarian cancer in Ovarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, Nuffield Department of Obstetrics and Gynaecology, University of Oxford as a Visiting Postdoctoral Research Scientist. He is distinguished gynecologic oncologist in Japan. His research is focused on understanding the molecular mechanisms of evolution of ovarian cancer, especially cancer stem cell, and on the development of novel therapeutic strategies for ovarian cancer.

Abstract:

The cancer stem cell hypothesis considers cancer stem cells as the main culprits of driving tumor initiation, metastasis, and resistance to conventional chemotherapy. Several previous studies have supported the premise that EpCAM proves to be a useful marker for the isolation of subsets enriched for cancer stem cells in many solid cancers, including ovarian cancer. We investigated the role of EpCAM in the resistance to platinum-based chemotherapy and the potential relevance of EpCAM to the clinical outcomes of patients with epithelial ovarian cancer. Here, we have showed that ovarian cancers containing high levels of EpCAM have a significantly much lower probability of achieving overall responsive rates after first-line platinum-based chemotherapy. Furthermore, multivariate analysis demonstrated that EpCAM expression in primary tumors is an independent risk factor for tumor resistance to chemotherapy, indicating that EpCAM expression is a predictive biomarker of chemotherapeutic response. Consistent with these clinical observations, in in vitro assays, we also found that treatment with chemotherapeutic agents enhances the cell surface expression of EpCAM in ovarian cancer cells. In association with anti-apoptotic mechanisms, the subpopulation of EpCAM-positive cancer cells showed a significantly higher viability than EpCAM-negative cells in response to chemotherapy. In an in vivo mouse model, platinum agents preferentially eliminated EpCAM-negative cells in comparison with EpCAM-positive cells, indicating that the remaining subpopulation of EpCAM-positive cells contributes to tumor recurrence after chemotherapy. Finally, we revealed that an increased expression of EpCAM in primary tumors was involved in a shortened overall- and progression-free survival in ovarian cancer patients. Our findings highlight the clinical significance of EpCAM in the resistance to chemotherapy and provide a rationale for EpCAM-targeted therapy to improve chemoresistance in ovarian cancer patients. Targeting EpCAM should be a promising approach to effectively eradicate the cancer stem cells as the putative root of ovarian cancer.

Biography:

Diler U S Altay is working as Assistant Professor in Ordu University. She completed her primary, secondary and high school education in Ordu. She graduated from the Department of Biochemistry at Ege University, Turkey. After working in the private sector for a short time, she completed her PhD in the Department of Biochemistry at Karadeniz Technical University in 2015 and was appointed as Assistant Professor at Ordu University in January 2016. She is still continuing her studies at Ordu University. She has published articles in three national and 19 international journals. Her work areas include cancer modeling, cachexia, weight loss hormone, oxidant-antioxidant system in animals.

Abstract:

Background: Piwi interacting RNA (piRNA) is the main class of small non-coding RNA molecules expressed in animal cells. Some of the piRNAs expression increases and shows oncogenic properties; while on the other hand, some of their expression decreases and shows tumorigenic properties in specific cancer types.

Objective: The present research is in comparison within normal and tumor renal biopsy specimens taken from patients with clear cell renal cell carcinoma (RCC), and in kidney tissue samples of non-transfected RCC patients who were operated for different reasons, two possible piRNAs (piR -36707 and piR-36741) expression levels, which are not related before but probably related to RCC.

Methodology & Theoretical Orientation: Between January 2016 and January 2017, formalin-fixed paraffin embedded (FFPE) specimens were obtained from 19 patients who had undergone partial or radical nephrectomy for diagnostic purposes and who had a clear cell RCC diagnosis in urology and pathology in the Ondokuz Mayıs University, Faculty of Medicine (OMÜTF). Tumor tissue sample and a healthy tissue sample from the same patient were included in the study. FFPE was made from tissue using a total RNA isolation kit. The piRNA-specific cDNA synthesis kit was used to convert the resulting piRNA into cDNA. piR-36707 and piR-36741 expression levels were measured using commercially available primers and real-time PCR kit specific to these piRNAs. Statistical significance analysis of the levels of piRNA expression was performed between the two groups.

Findings: Expression levels of piR-36707 and piR-36741, calculated by the comparative 2-ΔΔCt curve between tumor and normal kidney tissues, are given in comparison in Figure 1. The higher expression levels of piR-36707 and piR-36741 in tumor tissues than normal tissues give them a potential oncogenic function. However, when this relationship was examined by statistical methods, it was seen that p value was above 0.05 for both piRNAs and these changes were not significant.

Conclusion & Significance: According to the literature, this is the first study that relates to clear cell RCC pathogenesis and piR-36707 and piR-36741 genes. Prospectively, all genes in the target of piR-36707 and piR-36741 are studied as panels to achieve universal and comprehensive data for the pathogenesis of clear cell RCC.

Biography:

Rabah Iratni completed his PhD in Cellular and Molecular Biology from the University Joseph Fourier Grenoble 1 (France) and Post-doctorate from the University of Medicine and Dentistry of New Jersey (USA). He is currently a Professor at the United Arab Emirates University. His lab focuses on the discovery of new biologically active natural products, to evaluate their potential as therapeutic agents against breast cancer and determine their mechanism(s) of action. He also has a strong interest in the understanding of the epigenetic basis of cancer with focus on breast cancer. He has authored several papers in prestigious journals including Cell, Science, Molecular Cell, Genes & Development, PNAS, etc.

Abstract:

We have previously showed that carnosol significantly inhibited the viability and colony growth of triple negative breast cancer cells and induced ROS-dependent beclin-1-independent autophagy and subsequent apoptotic cell death. Here were analyzed the molecular mechanism through which carnosol exerts its anti-cancer activity. Mechanistically, we found that carnosol inactivated the AKT/mTOR pathway by promoting the proteasome-dependent degradation of both proteins. Strikingly, we also found that carnosol targets Stat3 to degradation. Proteasome inhibition restored these proteins to a level comparable to control cells. The proteasomal degradation of mTOR, which occurred as early as 30 minutes post- carnosol treatment was concomitant with an overall increase in the level of ubiquitinated proteins and translated stimulation of proteolysis by the proteasome. Interestingly, we found that the treatment of the breast cancer cells with N-acetylcysteine, an ROS inhibitor, not only restored AKT/mTOR/Stat3 proteins to a level comparable to control cells, but also dramatically reduced carnosol-induced cell death and blocked the activation of autophagy and apoptosis. Our findings demonstrate that carnosol exerts its anti-breast cancer activity through stimulation ubiquitin proteasome system which consequently triggers both autophagy and apoptosis, making it a potential and valuable source of novel therapeutic cancer drug.

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.

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.

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.

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.

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 3^rd 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).

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.

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.