Day 1 :
Keynote Forum
Diana Anderson
University of Bradford,UK
Keynote: Sensitivity and Specificity of the Empirical Lymphocyte Genome Sensitivity (LGS) Assay: Implications for Improving Cancer Diagnostics
Time : 9:40-10:15
Biography:
Professor Anderson holds the Established Chair in Biomedical Sciences at the University of Bradford. She obtained her first degree in the University of Wales and second degrees in the Faculty of Medicine, University of Manchester. She has an H index of 57, 450+ peer-reviewed papers, 8 books, has successfully supervised 26 PhDs, and been a member of editorial boards of 10 international journals. She has been or is Editor in Chief of a book Series on toxicology for J.Wiley and sons and the Royal Society of Chemistry respectively. She gives key note addresses at various international meetings. She is a consultant for many international organisations, such as the WHO, NATO, TWAS, UNIDO and the OECD
Abstract:
Background: This study examined differences in the sensitivity to genomic damage of lymphocytes derived from cancer patients, pre/suspect cancer patients and normal healthy volunteers. rnrnMethods: We investigated responses from 208 individuals: 20 melanoma, 34 colon cancer, 4 lung cancer patients (58); 18 suspect melanoma, 28 polyposis, 10 COPD patients (56) and 94 healthy volunteers. The natural logarithm of the Olive tail moment was plotted for exposure to UVA through 5 different agar depths (100 cell measurements/depth) and analysed using a repeated measures regression model.rnrnFindings: Genomic damage in lymphocytes from cancer patient samples plateaued and did not decrease as UVA intensity decreased. In comparison, lymphocyte response patterns for healthy individuals returned towards control values as UVA intensity decreased. The responses for samples from pre/suspected cancers patients were intermediate. All cancers tested exhibited comparable responses. Results indicated that lymphocyte sensitivity was cancer status dependant, thus an analyses of Receiver Operating Characteristic curves was undertaken on 208 individuals. The mean log Olive tail moments, for all cancers plus pre/suspected-cancer versus controls gave a value for the area under the curve of 0.87 (95% CI: 0.82, 0.92); for cancer versus pre/suspected-cancer plus controls the value was 0.89 (95% CI: 0.83, 0.95); and for cancer alone versus controls alone (excluding pre/suspected-cancer), the value was 0•93 (95%CI: 0.88, 0.98). For all 3 values, p<0.001. Interpretation: Results indicated that characterisation of differences in lymphocyte sensitivity to UVA enabled discrimination between cancer patients, pre/suspect cancer patients and healthy volunteers. This relationship could be used in an assay that functions as a stand-alone test or as a possible adjunct to other tests as part of a detection programme for cancer. Biography Professor Anderson holds the Established Chair in Biomedical Sciences at the University of Bradford. She obtained her first degree in the University of Wales and second degrees in the Faculty of Medicine, University of Manchester. She has an H index of 57, 450+ peer-reviewed papers, 8 books, has successfully supervised 26 PhDs, and been a member of editorial boards of 10 international journals. She has been or is Editor in Chief of a book Series on toxicology for J.Wiley and sons and the Royal Society of Chemistry respectively. She gives key note addresses at various international meetings. She is a consultant for many international organisations, such as the WHO, NATO, TWAS, UNIDO and the OECDrn
Keynote Forum
Martin Kristensson
Visiopharm ,Denmark
Keynote: Optimizing HER2 assessment in breast cancer - application of automated image analysis
Time : 10:15- 10:50
Biography:
Martin has been with Visio pharm since 2011 where he currently works as the VP, Technical Sales for Europe. He received his M.Sc. in Biomedical Engineering from the Technical University of Denmark in 2011, specializing in Signal and Model based Diagnostics, combined with Image Diagnostics and Radiation Physics. In 2014, he became a certified Project Manager at Copenhagen Business Academy. He has provided numerous research algorithms to researchers, enabling them to create quantitative histology data and publish papers, and continuously supports pathology laboratories in the transition into digital pathology.
Abstract:
Human epidermal growth factor receptor 2 (HER2) is a receptor for circulating growth factor, stimulating uncontrolled cell proliferation. Trastuzumab reacts with HER2 and arrests the cells in the G1 phase. Immune system-directed cell killing is probably also involved in the anti-cancer effect. In breast cancer, overexpression of HER2 occurs in 15%, and analysis of HER2 expression is therefore pivotal for treatment decision. In a cohort of 462 patients, stained with Roche’s ready-to-use HER2 test. The HER2-CONNECT algorithm evaluates the IHC staining reaction of HER2, based on cell membrane connectivity. The connectivity translates into the classic diagnostic score for HER2 expression (0, 1+, 2+ or 3+) in agreement with the ASCO/CAP guidelines. The automated reading was compared to manual reading, and for the borderline (2+) to manual reading of the HER2 gene expression on fluorescence in situ hybridization (FISH). Manual reading demonstrated a sensitivity of 85.0% and a specificity of 86.0% with 14.1% inconclusive samples. Using HER2-CONNECT, sensitivity increased to 97.6% and specificity to 95.5%. Less than 4.5% of the cases were deemed inconclusive. Total agreement when comparing HER2-CONNECT with manual IHC supplemented by FISH in borderline cases was 92.8%. Using the HER2-CONNECT digital image analysis algorithm based on IHC detection of HER2 protein expression on tumour cell membranes, less than 4.5% of the cases were inconclusive whether overexpressed or not. Compared to manual reading, the need for supplementary FISH testing is reduced by 67.7%. In the routine diagnostic setting, this would have significant impact on cost reduction and turn-around-time.
- 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.