Day 3 :
- Oncology & Organ Specific Cancer
Session Introduction
Ajay Singh
Mitchell Cancer Institute, USA
Title: Understanding and Overcoming chemoresistance of pancreatic cancer
Time : 11:10-11:35
Biography:
Ajay Singh, is a tenured Associate Professor of Oncologic Sciences and Head of Health Disparities in Cancer Research Program at the University of South Alabama Mitchell Cancer Institute (USAMCI). He received a Master’s degree in Biotechnology from Aligarh Muslim University and graduated from the Devi Ahilya University, Indore, India. He completed Post-doctoral training in the Department of Biochemistry and Molecular Biology at University of Nebraska Medical Center, Omaha, Nebraska. He later joined as a research faculty in the same department, and moved to USAMCI in 2009. Major focus of research in his lab is to understand the role of tumor microenvironment (TME) in cancer progression, metastasis and therapeutic resistance. He has received funding from state and several federal agencies (NCI, NSF and DoD) to support his research activities. He also serves on regional, national and international panels to review research proposals for funding considerations.
Abstract:
Despite a few breakthroughs in therapy, pancreatic cancer (PC) remains a therapeutic challenge for clinicians and translational researchers. Thus, it is important that we develop an improved understanding of the mechanisms underlying the aggressive and drug-resistant nature of pancreatic cancer to help in the designing of novel and effective therapeutic strategies. Emerging data suggest a pivotal role of tumour-stromal interaction in PC chemoresistance. In this regard, we have found an important role of CXCL12/CXCR4 signalling axis in conferring chemoresistance (by potentiating intrinsic survival mechanisms in tumour cells) and facilitating tumour-stromal interaction (through induction of sonic hedgehog; SHH) in PC. Moreover, we have observed CXCR4 up-regulation in gemcitabine-treated PC cells, reinforcing the role of CXCL12/CXCR4 signalling in PC chemoresistance. Additionally, we have conducted laboratory and preclinical studies to examine the therapeutic efficacy of combination therapy targeting CXCR4 and hedgehog signaling pathways alone and in combination with gemcitabine. PCCs/PSCs co-culture treated with gemcitabine (GEM) alone or in combination with CXCR4 antagonist (AMD3100) and/or hedgehog inhibitor (GDC-0449) yielded important findings. Inhibition of either CXCL12/CXCR4 (by AMD3100 treatment) or hedgehog (by GDC-0449 treatment) pathway led to PSCs-co-culture-induced chemoresistance, while co-inhibition of both of these pathways caused almost complete abrogation of co-culture induced chemoresistance of PC cells. In preclinical studies using orthotopic pancreatic tumour xenografts in mice, we observed that tumor growth was suppressed by the treatment of GEM, AMD3100 and GDC-0449 alone or in combination to variable extents. Notably, the most significant anti-tumor effects were seen in the mice group that received GEM along with AMD3100 and GDC-0499. Tumors were regressed completely in 30% of the mice that received this combination treatment of all three drugs. Moreover, livers of all the mice receiving this combination treatment were also completely free from metastatic nodules, whereas highest incidence of metastasis was observed in mice-treated with GEM+GDC-0499 followed by GEM and vehicle-treated mice (when the metastatic incidence was normalized to primary tumor burden). Our findings thus provide a hope that, in due course, we may be able to formulate novel strategies for effective therapeutic care of pancreatic cancer patients.
Stephanie Notttrott
Stephanie Notttrott, Isenbruck Bösl Hörschler LLP, Germany
Title: Patent protection for diagnostics and therapeutics - The essentials and importance of second medical use patents in precision medicine
Time : 11:35- 12:00
Biography:
Stephanie Nottrott is a Human Biologist by training and partner of the Patent Law firm Isenbruck Bösl Hörschler LLP. After having earned her PhD from the Max- Planck-Society in the field of Biochemical Protein-RNA research, she conducted her Post-doctoral studies in the Program of Molecular Medicine at the UMASS Medical School in Worcester, MA, USA, before entering the field of patent law as a scientific advisor in an international law firm in NYC, USA. She is qualified as a Patent, Trademark and Design Attorney and advises and represents clients from various businesses before the European and German Patent and Trademark Offices.
Abstract:
Obtaining broad product protection for pharmaceutical drugs or medical indications is becoming more and more difficult in an increasingly competitive pharmaceutical field as well as in light of the exploding rate of published medical prior art. Moreover, the patentability of medicinal inventions is subject to different restrictions in different jurisdictions. Patient specific treatment options, dosage regimes, next-generation genetic screening methods including the identification and characterization of particular patient subgroups for the application of individual and personalized diagnostic and therapeutic treatment regimes are currently considered the big challenge in the field of precision medicine. These aspects will lay the ground for important future business models in the pharmaceutical industry. As a result, patent protection in form of second medical use (previously so called “Swiss-type”) claims, taking into account the vast majority of bioinformatics results obtained from big data analysis, will become more and more important for biopharmaceutical market concepts in the near future. The presentation will elucidate the legal criteria which have to be fulfilled to successfully obtain patent protection for personalized medical applications in Europe in the first place, and what might be necessary to validly enforce these intellectual property rights against third parties´ interests.
Seema Singh
Mitchell Cancer Institute, USA
Title: The chemopreventive potential of silver nanoparticles against UVB-induced skin carcinogenesis.
Time : 12:00-12:25
Biography:
Seema Singh is an Ass. Professor of Oncologic Sciences at University of South Alabama Mitchell Cancer Institute (USAMCI), Mobile, AL, USA. She earned hers PhD from the University of Aligarh M University, Aligarh India in 2001. After completing her PhD. She carried out postdoctoral research in cancer biology at University of Nebraska Medical Center, Omaha, NE, USA. She joined Mitchell Cancer Institute at The University of South Alabama in 2009 and has been recognized as expert in cancer biology and in cancer pathogenesis in particular.
Abstract:
Solar ultraviolet (UV) radiation, particularly its UVB component, is an established cause of human skin carcinogenesis due to its ability to cause DNA damage in skin cells. Although several sunscreen formulations have been developed and commercialized to limit or minimize UVB exposure to skin cells; incidence of skin cancer has continued to increase suggesting their limited or no efficacy in preventing UV-induced skin cancer occurrence. Recently, we revealed the potential of silver nanoparticles (AgNPs; ≤ 50 nm) against UVB radiation-induced DNA damage in human keratinocytes (HaCaT). Here, we performed preclinical evaluation of chemopreventive efficacy of AgNPs against UVB-induced skin tumorigenesis in SKH-1 hairless mouse model. The different concentrations (20 and 40 mg/kg) of AgNPs mixed with hydrophilic cream base were uniformly applied topically onto the dorsal area of mouse skin prior to UVB-irradiation to assess chemopreventive efficacy in vivo for several weeks. The UVB only treatment group showed tumor formation within 13 weeks, and had high incidence (93.3%) rate by the end of the study (29 weeks). Interestingly, the pretreatment of mice with AgNPs significantly increased the latency period (6-9 weeks) of UVB-induced tumor formation. Moreover, overall tumor incidence was found to be significantly decreased (50 and 78%; in 20 and 40 mg/kg respectively) as compared to AgNPs-untreated mice. Tumor multiplicity and average tumor volume/tumor-bearing mouse were also observed to be significantly reduced in AgNPs-treated mice. Additionally, AgNPs treatment alone for 29 weeks did not induce any apparent signs of toxicity and changes in the body weight suggesting the safety of AgNPs. Altogether, these findings suggest that AgNPs are potential chemopreventive agents against UVB radiation-induced skin carcinogenesis and thus opening the ways for human applications.
Michael Retsky
Harvard TH Chan School of Public Health, USA
Title: Perioperative use of NSAID might prevent early relapses in breast and other cancers: An upstream approach
Time : 12:25-12:50
Biography:
Michael Retsky made a career change to cancer research thirty years ago. He is on staff at Harvard TH Chan School of Public Health and faculty at University College London. He was on Judah Folkman’s staff at Harvard Medical School for 12 years. Retsky is Editor of a Nature/Springer book on breast cancer to be published in 2016 and Editor-in-Chief of the Journal of Bioequivalence and Bioavailability. He is a founder and on the Board of Directors of the Colon Cancer Alliance and has published more than 60 papers in physics and cancer.
Abstract:
A bimodal pattern of hazard of relapse among early stage breast cancer patients has been identified in multiple databases from US, Europe and Asia. We are studying these data to determine if this can lead to new ideas on how to prevent relapse in breast cancer. Using computer simulation and access to a very high quality database for patients treated with mastectomy only, we proposed that relapses within 3 years of surgery are stimulated somehow by the surgical procedure. Most relapses in breast cancer are in this early category. Retrospective data from a Brussels anesthesiology group suggests a plausible mechanism. Use of ketorolac, a common NSAID analgesic used in surgery was associated with far superior disease-free survival in the first 5 years after surgery. The expected prominent early relapse events in months 9-18 are reduced 5-fold. Transient systemic inflammation accompanying surgery (identified by IL-6 in serum) could facilitate angiogenesis of dormant micrometastases, proliferation of dormant single cells, and seeding of circulating cancer stem cells (perhaps in part released from bone marrow) resulting in early relapse and could have been effectively blocked by the perioperative anti-inflammatory agent. If this observation holds up to further scrutiny, it could mean that the simple use of this safe, inexpensive and effective anti-inflammatory agent at surgery might eliminate early relapses. We suggest this would be most effective for triple negative breast cancer and be especially valuable in low and middle income countries. Similar bimodal patterns have been identified in other cancers suggesting a general effect.
Xia Liu
Institute of Forensic Science, China
Title: Human borna disease virus infection impacts host proteome and histone lysine acetylation in human oligodendroglia cells
Time : 14:00-14:25
Biography:
Xia Liu has completed her PhD from Chongqing Medical University. She is working in Institute of Forensic Science, Ministry of Justice, P R China. She has published more than 11 papers in reputed journals.
Abstract:
Borna disease virus (BDV) replicates in the nucleus and establishes persistent infections in mammalian hosts. Most publications implicating BDV in human disease have focused on neuropsychiatric disorders including unipolar depression, bipolar disorder and schizophrenia; however, BDV has also been linked to brain tumours (glioblastoma multiforme). A human BDV strain was used to address the first time, how BDV infection impacts the proteome and histone lysine acetylation (Kac) of human oligodendroglia (OL) cells, thus allowing a better understanding of infection-driven pathophysiology in vitro. Proteome and histone lysine acetylation were profiled through stable isotope labelling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Histone acetylation changes were validated by biochemistry assays. Post BDV infection, 4383 quantifiable differential proteins were identified. Sixteen of the thirty identified Kac sites in core histones presented altered acetylation levels post infection. BDV infection appears to preferentially dysregulate membrane, nuclear, and chromosomal host protein expression while affecting metabolic pathways, immune response, DNA replication, DNA repair, and transcription regulation. BDV infection was found to affect histone acetylation of specific lysine residues. Moreover, BDV infection affected the expression of many transcription factors, several histone acetyltransferases and histone deacetylases. As histone Kac epigenetically regulates gene transcriptional activation, the differential acetylation of specific lysine residues may have impacted the changes in the host proteome profile.
Yan-Shen Shan
Cheng Kung University, Taiwan
Title: Blockade of autophagy reduces pancreatic cancer stem cell activity and potentiates the tumoricidal effect of gemcitabine
Time : 14:25-14:50
Biography:
Yan-Shen Shan has completed his MD and PhD from National Cheng Kung University. He is the Director division of Trauma and UGI cancer team in National Cheng Kung University Hospital. He has published more than 100 papers in reputed journals and has been serving as an Editorial Board Member of repute.
Abstract:
Cancer stem cells (CSCs) are considered responsible for the recurrence and chemoresistance of cancer. Dysregulated autophagy is highly prevalent in many types of cancer including pancreatic cancer and has been implicated in cytoprotection and tumor promotion. We plan to investigate the role of autophagy in regulating cancer stemness and chemoresistance of pancreatic cancer. In pancreatic cancer tissue microarrays, LC3 expression positively correlated with the expression of CSC markers aldehyde dehydrogenase 1 (ALDH1), CD44 and CD133 in pancreatic cancer tissues. High co-expression of LC3/ALDH1 was associated with both poor overall survival and progression-free survival. In pancreatic cancer cell lines, higher LC3-II expression was observed in the sphere-forming cells than in the bulk cells. Blockade of autophagy by silencing ATG5, ATG7 and BECN1 or the administration of autophagy inhibitor chloroquine markedly reduced the CSC populations, ALDH1 activity, sphere formation and resistance to gemcitabine in vitro and in vivo. Furthermore, osteopontin (OPN) was found to stimulate LC3-II, ALDH1, CD44 and CD133 expression in PANC-1 cells, whereas this effect could be prevented by OPN knockdown and autophagy blockade. After treatment with various inhibitors against the major signaling pathways downstream of OPN, only the inhibitor of NF-κB activation, BAY 1170-82, could effectively counteract OPN-induced autophagy and CSC activity. Pancreatic cancer patients manifesting high levels of OPN/LC3/ALDH1 and OPN/CD44/ CD133 had poor survival. Induction of autophagy mediated by OPN/NF-κB signaling is required for maintenance of pancreatic CSC activity. In conclusion, combination of gemcitabine with pharmacological autophagy inhibitors is a promising therapeutic strategy for pancreatic cancer.
B R Das
Research and Development, SRL Ltd., India
Title: Evaluation of actionable mutation (KRAS, BRAF and PIK3CA) in colon cancer: Determination of frequency, distribution pattern in Indian patients
Time : 14:50-15:15
Biography:
B R Das is working as the President-Research & Innovation at SRL Limited, Mumbai. Apart from R&D, he also acts as the Mentor of the Molecular Pathology and the Clinical Research Services of SRL. He has almost 30 years of experience in the area of Molecular Medicine. Before his association with SRL, he worked as a Professor in Medical Biotechnology for nearly 15 years. He has published more than 90 research papers in peer reviewed international journals. He acts as Scientific Advisory Committee Member, Visiting Professor and Research guide at several reputed institutes of India. Besides, he is an Editorial Board Member of World Journal of Experimental Medicine. He is also the current President of the Molecular Pathologists Association of India (MPAI).
Abstract:
Introduction: Presence of actionable mutations plays a significant role in tailoring therapy in colorectal carcinomas. Mutations of the KRAS, BRAF and PIK3CA genes have gained tremendous attention in recent times mainly because of their ability to determine therapeutic response to anti EGFR therapy. The present study evaluated the frequency, distribution pattern and its association with clinic pathological characteristics in Indian colorectal cancer (CRC) patients. Materials & Method: Presences of actionable mutations were screened in 204 colorectal carcinoma cases by direct sequencing using gene specific primers. Results: KRAS, BRAF and PIK3CA mutations were present in 23.5%, 9.8% and 5.9% respectively. KRAS codon 12 mutation was most frequent followed by codon 13 mutation. Five different Missense mutations at KRAS codon 12 (G12S, G12D, G12A, G12V, and G12C) and one substitution type at codon 13 (G13D) were observed. All mutations in BRAF gene were of V600E type, while amongst PIK3CA gene, E545K was the most recurrent mutation in addition to other mutations (T544I, Q546R, H1047R, G1049S, and D1056N). KRAS mutations were significantly higher in patients who were >50 years, and were associated with moderate/poorly differentiated tumours, while in contrast, BRAF mutations were more common in patients with <50 years age, more common in well differentiated and right sided tumours. No significant association of PIK3CA mutation with age, tumor differentiation, location, and other parameters was noted. Both KRAS and BRAF mutations were found to be mutually exclusive, interestingly, five cases showed concurrent mutation of KRAS and PIK3CA. Conclusion: In conclusion, the frequency of KRAS and BRAF mutations were similar to most of the worldwide reports. Further studies are warranted to evaluate their prognostic impact and response to targeted therapy.
Anitha Gopal
Fortis hospitals, India
Title: Challenges in treating Ca Nasopharynx, Ca Tonsil and post op Head neck cancers by Intensity Modulated Radiationtherapy
Time : 15:15-15:40
Biography:
Anitha Gopal has completed her MD in Radiation Therapy from Barnard Institute of Oncology at Madras Medical College in 2003. She is the Head of Oncology, Fortis Hospitals Bangalore, India, accredited to Joint Commission International (JCI). She has been awarded the Best Poster Award in AROI State Conference-2004 (Association of Radiation Oncologist of India Tamil Nadu and Pondicherry chapter) on “Volume reduction analysis and hearing function preservation in stereotactic radiotherapy of Vestibular schwannoma” representing as a registrar of Apollo. She participated in a paper presentation on her MD thesis study in AROI State Conference-2003 as a MD postgraduate. She won Best Paper Presentation Award on 2 rare case reports of Follicular Dendritic Cell Sarcoma in AROI State Conference-2005, and National Faculty in AROI National Conference-2007. She has a publication on “Follicular dendritic carcinoma of Medistinum” in the Journal of Neuroncology.
Abstract:
Globally with the advancement in technology and intensity modulated radiation therapy technique and thorough knowledge on the microscopic areas of spread of the head and neck tumours in defining PTV, CTV and dose prescription when treated either by radiation therapy alone or with concurrent chemotherapy and radiation therapy or as post-operative radiation therapy proved an increase in the locoregional control rate and 5 year survival rate in locally advanced head neck cancers by more than 60% and early disease by more than 75%. The CTV in tonsil should include pterygoid plates, medial pterygoids, retropharyngeal nodes, maxillary tuberosity, retrostyloid nodes, tongue base, GB sulcus, lateral pharyngeal wall. The CTV in nasopharynx posterior includes 1/3rd of tongue, medial part of clivus, pharyngeal space, skull base, inferior sphenoid sinus. The CTV in post-op head and neck cancers should be preoperative area of extent of tumour, post-op histopathology details and include microscopic involvement of the tumour, positive margins, extracapsular nodal spread includes skin in CTV, perineural spread the entire nerve involved will be the CTV, nodal stations involved and differential dose prescription of subsequent level will be the CTV in post-op Ca Buccal mucosa prefacial node, in postop Ca Retromolar trigone, Upper alveolus and tumors crossing the midline the CTV should include pterygoid muscles. In post-op Ca Tongue, the entire tongue and mandibular foramen would be the CTV. If pterygoid muscle is involved, temporalis is included in CTV.
Kuo-Hsiang Chuang
Taipei Medical University, Taiwan
Title: One-step mixing with anti-tumor/anti-CD3 bispecific antibody enhances tumor targeting and therapeutic efficacy of ex vivo expanded T cells
Time : 15:40-16:05
Biography:
Kuo-Hsiang Chuang completed his PhD degree in Biomedicine at Kaohsiung Medical University, Taiwan, in 2010. From March 2010 to January 2012, he joined Professor Tian-Lu Cheng’s group (Kaohsiung Medical University) as a Post-doctoral Fellow to study protein engineering, including the development of humanized antibodies and novel recombinant protein drugs. In February 2012, he became an Assistant Professor in Graduate Institute of Pharmacognosy, Taipei Medical University, Taiwan. Now, he focuses on several research fields, including: Reporter genes/non-invasive imaging systems, antibody engineering, immunotherapy, and type 1 diabetes.
Abstract:
Adoptive T cell transfer, involving the ex vivo expansion of cancer patient’s T cells and then intravenous injection back to the patient, can effectively mediate tumor regression and extend patient’s life. However, lack of tumor specificity of most expanded T cells and time-consuming of generating tumor-specific T cells severely restrict in vivo survival time and anti-cancer ability of these ex vivo expanded T cells. In this study, we developed bispecific antibodies (BsAbs) by fusing an anti-CD3 scFv to the C-terminus of a Fab against tumor-associated antigen, such as EGFR or PSMA, to form α-tumor/α-CD3 BsAbs. The anti-CD3 end of the BsAb could non-covalently bind to CD3+ T cells and the anti-tumor end of BsAb can endow T cells with specificity to EGFR+ or PSMA+ tumor cells. One-step mixing with BsAbs significantly enhanced the killing efficacy of CD3+ T cells against EGFR+ colon cancer cells and PSMA+ prostate cancer cells in vitro and in vivo. Contact of BsAb-armed T cells with EGFR+ or PSMA+ tumor cells dramatically increase the release of cytotoxic factors, including: perforin, granzyme, INF-γ, and TNF-α, from these T cells to kill tumor cells. The α-tumor/α-CD3 BsAbs offer a simple one-step method to confer tumor specificity to CD3+ T cells for enhanced tumor targeting and improved therapeutic efficacy.
Yathish Kumar
Karnataka cancer hopsital & research centre, India
Title: Dendritic cell vaccine therapy in breast cancer patients
Biography:
Yathish Kumar has completed his Master’s in Surgical Oncology with keen interest in molecular basis of cancer aetiology and treatment. He has established a dedicated cancer treatment unit at Bangalore. He trains young surgeons to Surgical Oncologist. He has keen interest in developing new, innovative and evidence based treatment protocols in cancer treatment especially by molecular/immunological methods.
Abstract:
Breast cancer continues to be a leading cause of death in Indian cancer patients. 20-30% of breast cancers relapse, despite of multi-modality treatments for the same. Although considered immunologically silent, breast cancer is recently treated or being tried to be treated with immunological treatment modalities. One such exciting modality is treatment with “dendritic cell vaccine”. As experimental therapy, dendritic cell therapy offers hope to those who have no options left in the course of their treatment and also to those few who want to avoid traditional chemotherapy and targeted therapy either in combination or alone. Dendritic cell vaccine is prepared by autologous method i.e. from the patient herself and is sensitised with various antigens including tumor cell lysates, interleukins, cytokines and other adjuvants. We present our experience in producing the dendritic cells and treating breast cancer patients at our centre in Bangalore, India. We have treated 14 breast cancer patients at various stages. Our method of harvesting and preparing dendritic cell from patients’ blood and activating the preparation is unique. We are currently offering these vaccines under a investigator driven protocol.
Mahdi Shahriari
Shiraz University of Medical Sciences, Iran
Title: Revisiting the value and role of anti-angiogenesis in solid tumors and the mechanism to inhibit angiogenesis, and their possible complications: Pediatric oncologists view
Time : 16:50-17:15
Biography:
Mahdi Shahriari is currently working as an Associate Professor in Department of Paediatrics in Shiraz University of Medical Sciences, Iran since 1994. He has published many articles in reputed national & international journals. His area of expertise includes Medicine, Oncology, Hematology, Pediatric Hematology, Pediatric Oncology, Hemophilia, Thalassemia & Cord Blood Stem Cell Transplantation.
Abstract:
Introduction: Avastin (Bevocituzomab) and Sorafenib are 2 drugs that has been used for relapsed, refractory, metastatic and advanced brain tumor and HCC respectively in paediatric age group, but there are numerous new drugs which has not been used yet. Method: Mechanism of action, evidence of effectiveness and complications of anti-angiogenesis drugs revisited using English language large data bases; in order to find evidences for using these drugs focusing on paediatric age group; their mechanism of actions and complications. Results: Angiogenesis is a crucial mechanism required for many physiological events. In physiological conditions, angiogenesis is a highly regulated phenomenon that normally occurs during embryonic development, wound healing. Blood vessels are needed for the supply of nutrients and oxygen and the disposal of waste products. Neoangiogenesis is a multistep process that involves vasodilatation, enhanced vessel permeability, stromal degradation and endothelial cell proliferation and migration resulting in the formation of new or extended capillaries. Principal pro angiogenesis factors are: Angiopoietin -1, Pleitropin, Angiotensis, Epidermal growth factor, Fibroblast growth factor, Hepatocyte growth factor, Insulin-like growth factor, Placental growth factor, Platelet-derived growth factor, Transforming growth factors (α and β) and Vascular endothelial growth factor. Principal of anti-angiogenesis factors are: endostatin, trombospondin, tissue inhibitors of metalloproteinases and vasostatin. Some agents targeting VEGF: Bevacituzomab (Avastin) which is anti VEGF monoclonal Antibody that specifically inhibits all major human isoforms of VEGF; So inhibits proliferation, permeability, invasion, migration and survival of endothelial cells. By this mechanism Avastin causes regression of tumor vasculature, normalization of surviving vasculature, and inhibition of new tumor vessel growth potentially improves capacity of chemotherapeutic drug delivery and inhibits tumor growth and metastasis. But Ramucirumab is an anti-VEGFR-2Antibody, and Aflibercept (VEGF Trap) is a Soluble VEGF Receptor. Another class of antiangiogenesis drugs are small-molecule inhibitors including: Snitinib, Sorafenib, Pazopanib and Regorafenib. Among them evidence strongly suggests Sorafenib for advanced or progressing HCC, because it inhibits activity of C-Kit, FLT-3, VEGFR-2, VEGFR-3 and PDGFR- β.But it should be emphasized that when a patients became resistant to these drugs he/she will progress more rapidly and will have distant metastasis. Conclusion: Evidence supports better selection of patients for starting anti- angiogenesis drugs, their cost and resistance to them should be considered.
Muhammad U Rashid
Shaukat Khanum Memorial Cancer Hospital and Research Centre, Pakistan
Title: Absence of the FANCM c.5101C>T mutation in BRCA1/2-negative triple-negative breast cancer patients from Pakistan
Time : 17:15-17:40
Biography:
Muhammad U Rashid studied Medicine in Pakistan and then pursued his PhD/Postdoctoral studies and further worked as Guest Scientist at German Cancer Research Centre, Heidelberg. He has established the first Cancer Genetic Lab in a tertiary care center, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, where he is working as a Senior Research Scientist & Head of Basic Sciences Research. He is also working as Associate Professor, Human Genetics, University of Health Sciences, Lahore. His aim is to create a bridge between laboratory and clinic through translational studies. He has published more than 30 papers in reputed journals.
Abstract:
Breast cancer (BC) susceptibility is connected with the Fanconi anemia (FA) pathway, since biallelic mutations in BRCA2 (FANCD1), PALB2 (FANCN), BRIP1 (FANCJ) and RAD51C (FANCO) have been shown to also cause FA. Recently, a novel mutation c.5101C>T in exon 20 of another FA gene, FANCM was reported among Finnish BRCA1/2-negative BC families with 3.5-fold increased frequency among triple negative BC (TNBC) cases compared with controls. Given that deleterious mutations in other FA genes (BRCA2, RAD51C) have previously been identified among TNBC patients from Pakistan, we investigated whether the FANCM c.5101C>T mutation is associated with TNBC in Pakistan. 117 BRCA1/2-negative TNBC patients and 188 controls were screened for c.5101C>T mutation, using denaturing high-performance liquid chromatography analyses followed by DNA sequencing of variant fragments. The median age of diagnosis was 28 years (range 18 – 67). None of the study subjects carried this mutation implying that c.5101C>T mutation does not or rarely contribute to TNBC in Pakistani population. Two other in silico predicted to be functional missense mutations were identified. A previously reported mutation, c.4931G>A was found in two unrelated early-onset (<30 years) TNBC patients (2/75; 2.7%) of Persian ethnicity but absent among controls suggesting that it may be disease-causative. A novel mutation, c.4936G>C was found in a control of Punjabi ethnicity with a family history of leukaemia. In summary, the FANCM c.5101C>T mutation was not identified in Pakistani TNBC patients. Further whole gene screening studies are warranted to clarify the role of the FANCM gene in TNBC predisposition in Pakistan.
- Oncology,Cancer Causes
Session Introduction
Gabriele Jaques,
University Hospital of Giessen and Marburg,Germany
Title: Comprehensive Studies of Oncology“ (CSO)
Biography:
Gabriele Jaques is currently working at University Hospital of Giessen and Marburg, Germany. She has been recognized as expert in internal medicine. Her research experience includes various programs, contributions and participation in different countries for diverse fields of study. Her research interests as a professor reflect in her wide range of publications in various national and international journals. Her research of interest is in the field Nutritional Medicine, internal medicine.
Abstract:
Cancer is one of the main causes of death in the Western world. In our ageing society the number of patients will continue to rise in the coming decades since the incidence of the disease is higher among the elderly. The treatment of patients with malignant tumours will therefore to be one of the main challenges in the near future and has therefore be dealt in an interdisciplinary context of several cognate disciplines in medicine. The early education of students in the field of cancer research was therefore the main aim to install a special component of a teaching programme, the “Comprehensive Studies of Oncology”. These accompanying studies parallel to the last part of their normal studies” offers the most interested students the opportunity to acquire additional knowledge and skills in the field of oncological research at a high standard. The, Comprehensive Studies of Oncology‟ are linked to the “Comprehensive Cancer Centre (CCC) In Marburg”. More than 70 students attended the last 10 years successfully the curriculum.
Apollon Karseladze
N. Blokhin Cancer Research Center,Russian Federation
Title: Impairment of vascularization of the surface covering epithelium induces ischemia and promotes malignization: a new hypothesis of a possible mechanism of cancer pathogenesis
Biography:
Dr. Apollon Karseladze , MD, PhD, DSc is a full professor of Pathology, head of the Department of pathology in the Russian Cancer Research Center ,Moscow . After finishing Medical Faculty in 1970 he continued his residency in pathology (1970-1975). He got his PhD in 1975 (dissertation “Morphometric peculiarities of reticular cells in Hodgkin disease”). 1976-1979 junior researchers in the Department of Pathology of Russian Cancer Research Centre, Moscow. 1979-1994 senior researchers in the Department of Pathology Moscow Herzen Oncological Research Institute. 1990 doctoral dissertation “Morphology of ovarian epithelial tumours”. 1994-2006 Leading researcher in the Department of Pathology, Russian Oncological Research Centre From 2006 up to date Head of the same department. WHO gynaecological cancer histological classification of 2003.
Abstract:
Purpose: To study the peculiarities of vascularization at the stromal-epithelial interface in different types of epithelia and their alterations in precancerous lesions. Material & Methods: Peritumoral tissues of 310 patients, tissues of 180 healthy persons and of 50 human embryos and foetuses have been taken. Traditional histological as well as immunohistochemical methods have been used. Results: The study reveals that the occurrence of blood capillaries in surface squamous epithelium is an ordinary event, both in healthy persons and in peritumoral regions of the patients with squamous cell carcinoma. As soon as precancerous dysplastic alterations start and progress the number of intraepithelial blood vessels simultaneously decreases, thus leading to ischemia which precedes or promotes malignization of the covering squamous epithelium. To compensate for the deficit in blood supply, the dysplastic cells penetrate deeper into the underlying stroma, commencing invasion. Thus, the cells destroy the subjacent stroma not because they are initially “malignant”, but due to ischemia which provokes the search for nutrients. Glandular epithelial coverings, (e.g. respiratory epithelium) do not contain blood vessels, since each cell is attached directly to the basal membrane and has more ample access to the blood supply. In squamous epithelium, only basal cells are in contact with the membrane and underlying stroma, the cells of the upper layer receiving nutrients through diffusion. Thus the cells of squamous epithelium are more vulnerable to blood deficiency. Metaplastic squamous epithelium has a markedly reduced vascularization and seems to be more sensitive to carcinogenic stimuli. High-grade dysplastic squamous epithelium and carcinoma in situ do not contain blood vessels at all. Furthermore, the specific composition of basal membrane for each type of epithelium may regulate the ingrowth of blood capillaries into surface linings. Conclusion: The process of redistribution of vascular network occurring at the interface of epithelial- stromal frontier plays an important role in maintaining the adequate metabolism of cells including those of epithelial covering. Impairment of this mechanism most probably promotes precancerous alterations (dysplasia).
Serraino Diego
Oncology Referral Centre,Italy
Title: The negative impact of tobacco smoking on survival after prostate cancer diagnosis.
Biography:
Serraino Diego, is currently working at Oncology Referral Centre, Italy. She has been recognized as expert in Cancer. Her research experience includes various programs, contributions and participation in different countries for diverse fields of study. Her research interests as a professor reflect in her wide range of publications in various national and international journals. Her research of interest is in the field Oncology.
Abstract:
Purpose: Tobacco smoking has been found to increase prostate cancer (PCa) mortality in cohorts of healthy men but its effects on prognosis of men with PCa are still unclear. This study investigated the role of smoking on long-term survival after PCa diagnosis. Methods: A retrospective cohort including 780 men with incident PCa previously enrolled (between 1995 and 2002) as cases in an Italian case-control study. Information on vital status up to 2013 (median follow-up 13 years) and cause of death were retrieved through health archives. Hazard ratios (HRs) of all cause and PCa-specific death and corresponding 95% confidence intervals (CIs) were calculated using Cox models, adjusting for Gleason score and major confounders. Results: Out of 263 PCa deceased patients, 81 died because of PCa. Smokers at PCa diagnosis reported increased risks of all cause (HR=1.5, 95% CI 1.1-2.2) and PCa death (HR=2.0, 95% CI 1.0-3.8) as compared to never smokers. Dose-response effects emerged according to smoking intensity (HRs for >15 cigarettes/day: 1.9, 95% CI 1.3-3.0, for all causes and 2.3, 95% CI 1.1-4.9 for PCa) and duration (HRs for >45 years: 1.7, 95% CI 1.1-2.6, for all causes and 2.6, 95% CI 1.2-5.5 for PCa). Conversely, former smokers at PCa diagnosis showed no statistically significant higher risks of PCa death. The effects of smoking were consistent in strata of Gleason score. Conclusions: Current smoking at PCa diagnosis negatively impacted PCa-specific, long-term survival, regardless of Gleason score. Our findings suggest that smoking could be a modifiable risk factor to improve prognosis of men diagnosed with PCa.
Eman Abdelzaher
Alexandria University,Egypt
Title: FGF18 as a Potential Biomarker in Serous and Mucinous Ovarian Tumors
Biography:
Eman Abdelzaher is an currently working as an Associate Professor Departments of Pathology Faculty of Medicine, University of Alexandria, Alexandria, Egypt. She has been recognized as expert in Neuropathology. Her research experience includes various programs, contributions and participation in different countries for diverse fields of study. Her research interests as a professor reflect in his wide range of publications in various national and international journals. Her research of interest is in the field of Neuropathology.
Abstract:
Fibroblast growth factor 18 (FGF18) has been suggested to play important roles in promoting progression of ovarian high-grade serous carcinoma. Our aim was to investigate FGF18 expression in the whole spectrum of serous and mucinous ovarian tumours, highlighting differences in expression within the adenoma-carcinoma sequence and differences between type-1 and type-2 tumours. We also aimed to test the prognostic significance of this expression and its relation to micro vessel density (MVD). We evaluated the immunohistochemical expression of FGF18 and CD31 in 103 ovarian tumours and statistically analysed their association with clinicopathological variables and patients’ outcome. FGF18 score increased significantly within the adenoma-carcinoma sequence for serous and mucinous tumours. MVD increased significantly only among serous tumours. FGF18 and MVD correlated significantly (overall and among serous tumours only) and were significantly higher in type-2 than type-1 tumours. Cox regression models were built. Independent predictors could not be determined due to multicollinearity between the predictors. However, the combination of International Federation of Gynaecology and Obstetrics (FIGO) stage, ovarian carcinoma type and or FGF18 score achieved the highest predictability of poor prognosis. FGF18 could play a role within the adenoma-carcinoma sequence in type-1 tumours and might modulate angiogenesis among serous tumours. Our findings further augment the differences between type-1 and type-2 tumours. The combination of FIGO stage, ovarian carcinoma type and or FGF18 score could predict poor prognosis among ovarian carcinoma patients. Our work identifies FGF18 in ovarian neoplasia as a promising field of research, although evaluation of the performance of the developed models is still needed.
- Cancer Causes, Cancer Diagnostics, Cancer Treatment and Therapy & Clinical Oncology
Session Introduction
Diana Anderson
University of Bradford, UK
Title: General overview of the Comet assay
Time : 11:10-11:35
Biography:
Diana Anderson has completed her PhD at the University of Manchester, UK in the Faculty of Medicine. She is the Established Chair in Biomedical Sciences at the University of Bradford. She has published more than 450 papers, 8 books, successfully supervised 30 PhD students, and has a Hirsch factor of 54. She is Editor-in-Chief of a Book Series for the Royal Society of Chemistry and is consultant to many international organisations, such as the World Health Organisation/ International Programme of Chemical Safety.
Abstract:
The comet assay measures DNA strand breaks in single cells. Cells in agarose on a microscope slide are lysed with detergent and high salt. Electrophoresis results in structures resembling comet tails formed by DNA fragments moving towards the anode. The assay is used for genotoxicity testing, ecotoxicity, human bio monitoring, molecular epidemiology and basic research into DNA damage and repair and effects of nanoparticles. This overview will consider examples from the author’s group and collaborators. These will include for genotoxicity testing the specificity and sensitivity of the assay, for ecotoxins that work with DBP halogenated acetic acids, for human biomonitoring and molecular epidemiology work with mother and babies, diabetes and lead-exposed children and for fundamental research drug resistant non-Hodgkin’s lymphoma patients over-expressing p53 mutant protein and lacking DNA repair. Most of this work is in somatic human lymphocytes and human sperm. Using sperm, the positive response to oestrogens can be diminished with anti-oxidants, suggesting a ROS involvement. Also as age increases in men so does DNA damage and in both cell types’ nanoparticles of zinc and titanium dioxide can also produce damage. When modified, it can be used as a blood test to predict cancer. From a regulatory viewpoint, the assay is regarded as an indicator test, but is incorporated into guidelines in some countries.
Diana Stanoeva
Histogenex, Belgium
Title: The march of pathologists into ‘Big Industry’ or the worries of a newly transformed surgical pathologist
Time : 11:35-12:00
Biography:
Diana Stanoeva has completed her PhD at the age of 35 years from Medical University in the city of Plovdiv, Bulgaria and is an Associate Professor at the same university. She is a Staff Pathologist at Histogenex, Antwerpen, Belgium – a premier companion diagnostic centre. She has published more than 25 papers in local and international journals.
Abstract:
Within the next 5 years, clinicians will be implementing targeted therapies based on the presence of specific biomarkers. Labs will be diagnosing cancer via liquid biopsies using blood or urine specimens, followed by locating the cancer and treating it using targeted therapy directed at the molecular mechanisms driving the disease. We as pathologist applaud the rigorous scientific methodology with all its advantages and disadvantages, but all these biomarkers provide only risk categories and numerical score for risk of recurrence or patient’s responsiveness to certain therapy. Yet, the decision is ‘human-based’ consideration involving oncologist-pathologist agreement on managing patient care unifying patient’s clinical presentation, molecular subtyping with standart clinicopathologic classification. How does the concept of personalized medicine affect pathology. What will be the primary role of a pathologist in 5 or 10 years? What current technologies in pathology are already absorbed by other specialties and what technologies could pathology absorb? If pathology goes for the change is it possible re-program our knowledge and capacity? The presentation focuses on the several options in the face of pathology necessary to keep path with the recent molecular techniques.
Apollon Karseladze
N. Blokhin Cancer Research Center, Russian Federation
Title: Impairment of vascularization of the surface covering epithelium induces ischemia and promotes malignization: A new hypothesis of a possible mechanism of cancer pathogenesis
Time : 12:00-12:25
Biography:
Apollon Karseladze, is a full professor of Pathology, Head of the Department of Pathology in the Russian Cancer Research Centre, Moscow. After finishing Medical Faculty in 1970, he continued his residency in Pathology (1970-1975). He got his PhD in 1975 (dissertation “Morphometric peculiarities of reticular cells in Hodgkin disease”). During 1976-1979, He served as a Junior Researcher in the Department of Pathology of Russian Cancer Research Centre, Moscow and during 1979- 1994 served as Senior Researcher in the Department of Pathology Moscow Herzen Oncological Research Institute. From 1994 to 2006, he served as Leading Researcher in the Department of Pathology, Russian Oncological Research Centre. From 2006 till date, he is serving as the Head of the same department.
Abstract:
Purpose: To study the peculiarities of vascularization at the stromal-epithelial interface in different types of epithelia and their alterations in precancerous lesions. Material & Methods: Peritumoral tissues of 310 patients, tissues of 180 healthy persons and of 50 human embryos and foetuses have been taken. Traditional histological as well as immunohistochemical methods have been used. Results: The study reveals that the occurrence of blood capillaries in surface squamous epithelium is an ordinary event, both in healthy persons and in peritumoral regions of the patients with squamous cell carcinoma. As soon as precancerous dysplastic alterations start and progress the number of intraepithelial blood vessels simultaneously decreases, thus leading to ischemia which precedes or promotes malignization of the covering squamous epithelium. To compensate for the deficit in blood supply, the dysplastic cells penetrate deeper into the underlying stroma, commencing invasion. Thus, the cells destroy the subjacent stroma not because they are initially “malignant”, but due to ischemia which provokes the search for nutrients. Glandular epithelial coverings, (e.g. respiratory epithelium) do not contain blood vessels, since each cell is attached directly to the basal membrane and has more ample access to the blood supply. In squamous epithelium, only basal cells are in contact with the membrane and underlying stroma, the cells of the upper layer receiving nutrients through diffusion. Thus the cells of squamous epithelium are more vulnerable to blood deficiency. Metaplastic squamous epithelium has a markedly reduced vascularization and seems to be more sensitive to carcinogenic stimuli. High-grade dysplastic squamous epithelium and carcinoma in situ do not contain blood vessels at all. Furthermore, the specific composition of basal membrane for each type of epithelium may regulate the ingrowth of blood capillaries into surface linings. Conclusion: The process of redistribution of vascular network occurring at the interface of epithelial- stromal frontier plays an important role in maintaining the adequate metabolism of cells including those of epithelial covering. Impairment of this mechanism most probably promotes precancerous alterations (dysplasia).
Wen-Lung Ma
China Medical University Hospital, Taiwan
Title: Cholesterol Import and steroidogenesis are Biosignatures for gastric cancer progression
Time : 12:25-12:50
Biography:
Wen-Lung Ma, is currently working as an assistant Professor at Christian Hospital, Taiwan. He has been recognized as expert in Cancer Pathology, Endocrinology, and Sex Hormone Biology. His research experience includes various programs, contributions and participation in different countries for diverse fields of study. His research interests reflect in his wide range of publications in various national and international journals. His research of interest is in the field Cancer research, Oxidative stress, Antioxidants.
Abstract:
Androgens, oestrogens, progesterone and related signals are reported to be involved in the pathology of gastric cancer. However, varied conclusions exist based on serum hormone levels, receptor expressions, and in vitro or studies. This report used a web-based gene survival analyser to evaluate biochemical processes, including cholesterol importing via lipoprotein/receptors (L/R route), steroidogenic enzymes, and steroid receptors, in gastric cancer patients prognosis. The sex hormone receptors (androgen receptor, progesterone receptor, and oestrogen receptor ESR1 or ESR2), L/R route (low/high-density lipoprotein receptors, LDLR/ LRP6/SR-B1 and lipoprotein lipase, LPL) and steroidogenic enzymes (CYP11A1, HSD3B1, CYP17, HSD17B1, HSD3B1, CYP19A1 and SRD5A1) were associated with 5-year survival of gastric cancer patients. The AR, PR, ESR1 and ESR2 are progression promoters, as are the L/R route LDLR, LRP6, SR-B1 and LPL. It was found that CYP11A1, HSD3B1, CYP17, HSD17B1 and CYP19A1 promote progression, but dihydrotestosterone (DHT) converting enzyme SRD5A1 suppresses progression. Analysing steroidogenic lipidome with a hazard ratio score algorithm found that CYP19A1 is the progression confounder in surgery, HER2 positive or negative patients. Finally, in the other patient cohort from TCGA, CYP19A1 was expressed higher in the tumor compared to /that in normal counterparts, and also promoted progression. This work depicts a route-specific outside-in delivery of cholesterol to promote disease progression, implicating a host-to-tumor macroenvironmental regulation. In addition, this report also described the importance of steroidogenesis biochemical process in disease progression. It is valuable to implement CYP19A1 targeting therapy in gastric cancer patients, working toward unmet medical needs.
Biography:
Magalie Tardy holds a PhD in molecular and cellular physiology from University of Nice Sophia Antipolis. After completing her PhD, she is now completing her internship in medical oncology, at the department of oncology; centre Antoine Lacassagne in Nice, France. She is interesting in hematology and more particularly in lymphoma and autologous stem cell transplantation.
Abstract:
Background: Refractory or relapsed large B-cells lymphoma are usually treated with a high dose chemotherapy regimen followed by an autologous stem cells transplantation. BEAM (carmustine, etoposide, cytarabine, melphalan) or more recently Z-BEAM (ibritumomab tiuxetan and BEAM) are commonly used regimens, but recently carmustine availability became difficult. The purpose of this study was to evaluate the feasibility and the safety of replacing carmustine by bendamustine in a new Z-BeEAM regimen (ibritumomab tiuxetan, bendamustine, etoposide, cytarabine, melphalan) prior to autologous stem cell transplantation. Findings: This study was a retrospective analysis of six patients, with a median age of 60, treated by Z-BeEAM before autologous stem cell transplantation. We did not put in evidence any additional toxicities compared to conventional induction chemotherapy. The main toxicities were microsites (3 grade III among 6 patients), gastrointestinal (2 grade III vomiting and 2 grade III diarrhoea) and neutropenia (6 grade IV). Engraftment was successfully achieved for all patients. At the time of analysis of this study all patients were alive and in complete response based on the PET-CT evaluation. Conclusions: BeEAM plus ibritumomab tiuxetan combined regimen before autologous stem cell transplantation is feasible and safe in aggressive relapsing large B-cell lymphoma.
Mafalda Sofia Barros Gomes
Centro Hospitalar do Porto, Portugal
Title: The fetal risks from diagnostic use of radiation during pregnancy: A systematic review and proposal of a clinical protocol
Biography:
Mafalda Sofia Barros Gomes has completed her Degree in Basic Health Sciences in the Faculty of Medicine of the University of Porto, the best Medical School in Portugal, in 2012. Engaged in one of the biggest Hospitals in the country, she gained clinical experience in Hospital S. João, with internships in Hospital Pedro Hispano and Póvoa de Varzim-Vila do Conde Hospital Centre. In 2015 she finished her Master Degree in Medicine in the same Faculty of Medicine. Her thesis was recently published on an international journal with an impact factor of 1.6. Currently she is working at Porto’s Hospital Centre.
Abstract:
Aim: The study was conducted to analyse the existing literature about the fatal risks of radiation exposure, producing a clinical protocol to guide radiation exposure in a clinical setting. Methods: An initial query was made on PubMed: “Diagnostic radiography in pregnancy AND radiation”, with the limits “published from January 1st 1993 to December 31st 2013, in English or Portuguese”. The articles that presented our aim were analysed according to their MESH terms and created the final query: “((radiation) AND pregnancy) AND diagnostic imaging”. Research on April 15th of 2014, with the same limits, on PubMed gathered 688 articles; on SCOPUS 245 additional articles. After reading the title and abstract 298 articles remained. 179 allowed access to full text and were analysed according to inclusion and exclusion criteria. A total of 103 articles were used and an additional one regarding In utero radiation exposure from atomic bombs. The PRISMA statement was followed. Results: Deterministic effects like pregnancy loss, congenital malformations, growth retardation and neurobehavioral abnormalities have threshold doses greater 100-200 mGy, being the risk considered negligible at 50 mGy. No diagnostic exam exceeds this limit. The most crucial time to avoid radiation exposure is from the 8th to the 15th week of gestation. The risk of carcinogenesis is slightly higher than the general population, although very similar. Intravenous contrast is discouraged, except in highly-selected patients. Conclusion: Measures to diminish radiation are essential and affect the fatal outcome. Nonionizing procedures should be considered whenever possible and every radiology centre should have its own data on fatal radiation exposure.
Mafalda Sofia Barros Gomes
Centro Hospitalar do Porto, Portugal
Title: The fetal risks from diagnostic use of radiation during pregnancy: A systematic review and proposal of a clinical protocol
Time : 14:50-15:15
Biography:
Mafalda Sofia Barros Gomes has completed her Degree in Basic Health Sciences in the Faculty of Medicine of the University of Porto, the best Medical School in Portugal, in 2012. Engaged in one of the biggest Hospitals in the country, she gained clinical experience in Hospital S. João, with internships in Hospital Pedro Hispano and Póvoa de Varzim-Vila do Conde Hospital Center. In 2015 she finished her Master Degree in Medicine in the same Faculty of Medicine. Her thesis was recently published on an international journal with an impact factor of 1.6. Currently she is working at Porto’s Hospital Center.
Abstract:
Aim: The study was conducted to analyze the existing literature about the fetal risks of radiation exposure, producing a clinical protocol to guide radiation exposure in a clinical setting. Methods: An initial query was made on PubMed: “Diagnostic radiography in pregnancy AND radiation”, with the limits “published from January 1st 1993 to December 31st 2013, in English or Portuguese”. The articles that presented our aim were analyzed according to their MESH terms and created the final query: “((radiation) AND pregnancy) AND diagnostic imaging”. Research on April 15th of 2014, with the same limits, on PubMed gathered 688 articles; on SCOPUS 245 additional articles. After reading the title and abstract 298 articles remained. 179 allowed access to full text and were analyzed according to inclusion and exclusion criteria. A total of 103 articles were used and an additional one regarding In utero radiation exposure from atomic bombs. The PRISMA statement was followed. Results: Deterministic effects like pregnancy loss, congenital malformations, growth retardation and neurobehavioral abnormalities have threshold doses greater 100-200 mGy, being the risk considered negligible at 50 mGy. No diagnostic exam exceeds this limit. The most crucial time to avoid radiation exposure is from the 8th to the 15th week of gestation. The risk of carcinogenesis is slightly higher than the general population, although very similar. Intravenous contrast is discouraged, except in highly-selected patients. Conclusion: Measures to diminish radiation are essential and affect the fetal outcome. Nonionizing procedures should be considered whenever possible and every radiology center should have its own data on fetal radiation exposure.
Tanvi Sood
Shri Ram Murti Smarak Institute of Medical Sciences, India
Title: Prognostic factors and their correlation with staging in patients with Multiple Myeloma: A single centre study in North India
Biography:
Tanvi Sood finished her MBBS course from Bharati Vidhyapeeth University, Pune, India in the year 2013. She is currently pursuing Masters in Internal Medicine at SRMSIMS, Uttar Pradesh, India. She has been awarded Gold prize and rewarded scholarship for her academic achievements and scientific presentations, both National and International. Her work has been accepted and published in national as well as international journals. She was part of the Organising Committee of the International Conference MEDICINE UPDATE 2015 held at Bareilly, India. She has also participated in Phase 3 drug trials while working at Dr. Ram Manohar Lohia Hospital, PGIMER, New Delhi. She has special interest in Oncology and Endocrinology.
Abstract:
Introduction: Multiple myeloma is a neoplastic disorder characterized by proliferation of a single clone of plasma cells leading to varied clinical presentations. Various clinical and laboratory parameters have been established as prognostic factors but their correlation with staging systems has been sparingly studied in Indian population. Materials and Methods: A retrospective study was done over a period of 30 months at a tertiary care centre including 33 patients of Multiple Myeloma. Physical examination, radiological investigations and routine laboratory investigations including bone marrow examination, serum protein electrophoresis and serum β2-microglobulin levels were recorded. Patients were staged according to the Durie-Salmon Staging System (DSS) and the International Staging System (ISS) and correlation between prognostic markers and clinical stage was studied. Results: A total of 33 patients were included in the study, all of whom had M-band in the gamma region on serum protein electrophoresis. 51.5% patients presented with renal failure and its presence correlated positively with the stage of disease (0.643, P<0.001). Plasmacytosis showed a positive correlation with the stage of disease (0.351, p<0.045). A significant positive correlation was also found between the DSS and ISS (0.575, p<0.001). Haemoglobin, Serum β2-microglobulin levels, advanced age, Estimated Sedimentation Rate (ESR), serum creatinine and uraemia were other factors that significantly correlated with the clinical stage in our population. Conclusion: Both ISS and DSS correlate well as staging systems for Multiple Myeloma in the Indian population. Routine investigations like Haemoglobin, ESR, renal function tests and plasma cell percentage can be used for prognostication at initial presentation. Prognostic markers like serum β2-microglobulin and renal failure are strongly associated with more advanced stages of Multiple Myeloma.
Noura Ramadan
Suez Canal University, Egypt
Title: MicroRNA-21 expression in primary breast cancer tissue among female patients and its correlation with chromosome 17 aneusomy
Biography:
Noura Ramadan Abdel-Hamid is currently working as an Assistant Lecturer of Medical Genetics, Faculty of Medicine of Suez Canal University. She has studied Medicine in the Faculty of Medicine, Suez Canal University, Egypt. She has worked as a House officer, Faculty of Medicine, Suez Canal University from March 2009 to February 2010. She has also worked as a Demonstrator of Medical Genetics, Faculty of Medicine, Suez Canal University from December 2010 to February 2015.
Abstract:
Breast cancer (BC) is the most common cancer worldwide and amongst Egyptian women. Micro-RNA-21 (miR-21), on chromosome 17q21.3, is one of the most up-regulated microRNAs in cancer that silences multiple target genes involved in cancer-signaling pathways. The study assessed the correlation between the miR-21expression profile and numerical aberrations of chromosome 17 in BC tissues in female Egyptian patients. The study included 37 female patients with sporadic primary breast carcinoma, their age ranged from 31 to 65 years. Fresh breast tissue specimens were evaluated for miR-21 expression levels using reverse transcription-polymerase chain reaction technology and cytogenetic fluorescent in situ hybridization for chromosome 17 aneusomy. The miR-21 was upregulated 12.9-fold in BC tissues and over-expression was significantly associated with several clinicopathologic characteristics; as tumor size, tumor grade, advanced stage and poor prognostic index. In addition, chromosome 17 aneusomy was, profoundly, observed in BC patients. However, the large majority (73%) of patients had heterogeneous cell populations. Chromosome 17 copy number heterogeneity in cell populations were significantly associated with advanced clinical stage and higher miR-21 expression profile in BC tissues. In conclusion, in breast cancer, expression of microRNA-21 located on 17q21.3 was correlated with the chromosome copy number. Chromosome 17 aneusomy and microRNA-21 levels can serve as potential prognostic biomarkers in breast cancer tissues. Chromosome 17 aneusomy analysis by cell heterogeneity gives more useful information than analysis by copy number variation alone. Polysomy of chromosome 17 may explain the significant miR-21 over-expression while miR-21 up-regulation in monosomic cases needs further genetic evaluation to explain it.
Ming Zhao
Chinese PLA General Hospital, China
Title: Combined bevacizumab and stereotactic radiosurgery for the treatment of a child with recurrent medulloblastoma
Biography:
Ming Zhao has completed his PhD at the age of 30 years from Chinese PLA Medical College. He is working in the Neurosurgery Department, First Affiliated Hospital of Chinese PLA General Hospital. He has published more than 25 papers.
Abstract:
Medulloblastoma has a very poor prognosis in children regardless of the treatment employed. Currently, there is no standard treatment for recurrent or refractory cases. To date, there have been no reports on the use of bevacizumab with stereotactic radiosurgery against medulloblastoma. We report the case of a child with recurrent, refractory, medulloblastoma who was treated with both bevacizumab and stereotactic radiosurgery (Leksell Gamma Knife®, Elekta Instruments, Stockholm, Sweden). Following this combined treatment, the lesions targeted with radiosurgery showed complete response with minimal toxicity in less than 1 month. This is the first documented case of medulloblastoma treated with bevacizumab and stereotactic radiosurgery. The combined use of bevacizumab and stereotactic radiosurgery may represent a novel treatment against medulloblastoma in patients who are not surgical candidates, and should be investigated further. Prospective clinical trials should be considered in order to evaluate the effectiveness of this strategy.
- Extended Networking Session
Session Introduction
Low Wei Xiang Alvin
Singapore General Hospital,Singapore
Title: Oncological outcomes following robotic-assisted radical prostatectomy in a multiracial Asian population
Biography:
Low Wei Xiang Alvin is currently a resident trainee in the Department of Urology, Singapore General Hospital. Her research experience includes various programs, contributions and participation in different countries for diverse fields of study. Her research interests as a professor reflect in his wide range of publications in various national and international journals.
Abstract:
This study evaluates the oncological outcomes of RARP in a multiracial Asian population from a single institution. All suitable patients from 1st January 2003–30th June 2013 were identified from a prospectively maintained cancer registry. Peri-operative and oncological outcomes were analysed. Significance was defined as p < 0.05. There were n = 725 patients identified with a mean follow-up duration 28 months. The mean operative time, EBL and LOS were 186 min, 215 ml and 3 days, respectively. The pathological stage was pT2 in 68.6 % (n = 497/725), pT3 in 31.3 % (n = 227/725) and n = 1 patient with pT4 disease. The pathological Gleason scores (GS) were 6 in 27.9 % (n = 202/725), GS 7 in 63.6 % (n = 461/725) and GS ≥ 8 in 8.0 % (n = 58/725). The node positivity rate was 5.8 % (n = 21/360). The positive margin rates were 31.0 % (n = 154/497) and 70.9 % (n = 161/227) for pT2 and pT3, respectively, and decreasing PSM rates are observed with surgical maturity. The biochemical recurrence rates were 9.7 % (n = 48/497) and 34.2 % (n = 78/228) for pT2 and pT3/T4, respectively. On multivariate analysis, independent predictors of BCR were pathological T stage and pathological Gleason score. Post-operatively, 78.5 % (n = 569/725) of patients had no complications and 17.7 % (n = 128/725) had minor (Clavien grade I–II) complications. This series, representing the largest from Southeast Asia, suggests that RARP can be a safe and oncologically feasible treatment for localised prostate cancer in an institution with moderate workload.
Yan-Shen Shan
National Cheng Kung University Hospital,Taiwan
Title: Blockade of autophagy reduces pancreatic cancer stem cell activity and potentiates the tumoricidal effect of gemcitabine
Biography:
Yan-Shen Shan has completed his MD and PhD from National Cheng Kung University. He is the Director division of Trauma and UGI cancer team in National Cheng Kung University Hospital. He has published more than 100 papers in reputed journals and he has been serving as an Editorial Board Member of repute.
Abstract:
Cancer stem cells (CSCs) are considered responsible for the recurrence and chemoresistance of cancer. Dysregulated autophagy is highly prevalent in many types of cancer including pancreatic cancer and has been implicated in cytoprotection and tumor promotion. We plan to investigate the role of autophagy in regulating cancer stemness and chemoresistance of pancreatic cancer. In pancreatic cancer tissue microarrays, LC3 expression positively correlated with the expression of CSC markers aldehyde dehydrogenase 1 (ALDH1), CD44 and CD133 in pancreatic cancer tissues. High co-expression of LC3/ALDH1 was associated with both poor overall survival and progression-free survival. In pancreatic cancer cell lines, higher LC3-II expression was observed in the sphere-forming cells than in the bulk cells. Blockade of autophagy by silencing ATG5, ATG7 and BECN1 or the administration of autophagy inhibitor chloroquine markedly reduced the CSC populations, ALDH1 activity, sphere formation and resistance to gemcitabine in vitro and in vivo. Furthermore, osteopontin (OPN) was found to stimulate LC3-II, ALDH1, CD44 and CD133 expression in PANC-1 cells, whereas this effect could be prevented by OPN knockdown and autophagy blockade. After treatment with various inhibitors against the major signaling pathways downstream of OPN, only the inhibitor of NF-κB activation, BAY 1170-82, could effectively counteract OPN-induced autophagy and CSC activity. Pancreatic cancer patients manifesting high levels of OPN/LC3/ALDH1 and OPN/CD44/CD133 had poor survival. Induction of autophagy mediated by OPN/NF-κB signaling is required for maintenance of pancreatic CSC activity. In conclusion, combination of gemcitabine with pharmacological autophagy inhibitors is a promising therapeutic strategy for pancreatic cancer.