Day 2 :
Northwestern University-Feinberg School of Medicine, USA
Hau C Kwaan completed his MBBS in 1952 and MD in 1958 from University of Hong Kong. He completed his fellowship in Columbia University College of Physicians and Surgeons in New York in 1959. He is board certified in Internal Medicine, Hematology and Medical Oncology. He is the Marjorie C Barnett Professor of Hematology-Oncology and Professor of Medicine at the Feinberg School of Medicine, Northwestern University. He has published more than 400 papers in peer reviewed journals and edited 3 books on Thrombosis. He is the Senior Editor of the seminars in Thrombosis and Hemostasis.
Acute promyelocytic leukemia (APL) has distinct molecular, morphologic and clinical characteristics that set it apart from other forms of acute myelogenous leukemia. The majority of patients at presentation have varying degrees of hemostatic and fibrinolytic abnormalities, resulting in increased thrombotic and bleeding complications. The coagulation profile shows signs of activated coagulation with increased fibrinopeptide A, prothrombin fragment 1+2 and thrombin-antithrombin complexes and of consumption of coagulation factors with increase fibrin D-dimer and decreased fibrinogen. Fibrinolytic abnormalities are also present with increased t-PA, u-PA, and plasmin and decreased PAI-1 and α2-antiplasmin. The excessive fibrinolysis is characterized by increased expression of u-PA, t-PA and the annexin A2/S100A receptor in the leukemic promyelocytes. Thrombin activatable fibrinolytic inhibitor (TAFI) is reduced. These changes are reversed by differentiation therapy with ATRA or arsenic trioxide. The clinical bleeding from coagulopathy generally abates by 5-7 days, but the abnormal coagulation and fibrinolytic profiles return to normal after 14 days or longer. Though differentiation therapy results in an improved clinical outcome and a molecular remission in over 90% of patients, the early death rate in the first 30 days of diagnosis remains unacceptably high at 5-10%. The major cause of this is bleeding, commonly as intracranial hemorrhage. The latter may be related to increased expression of annexin A2 in the cerebral microvasculature. Unfortunately, an effective therapeutic approach to correct the bleeding complications is still elusive. The APL patient has also an increased thrombosis risk of up to 10%, an incidence that has not been changed by differentiation therapy.
- Pancreatic and Colorectal Cancer l Reproductive Cancers l Nursing Oncology l Cancer Therapy l Scenario of Cancer
University of Debrecen, Hungary
Gaspar Banfalvi studied Pharmacy and completed his Doctorate in Szeged (1972), spent two years at the Institute for Drug Research in Budapest (1972-1974). He completed his Degrees (CSc, DSc and Med Habil) at the Department of Medical Chemistry, Budapest (1974-2000). He held the position of Chair in the Department of Biology at University of Debrecen (2000-2005). He teaches Medical Chemistry, Biochemistry, Cell Biology, Genetics and Physiology. He visited: for four years BBRI-Harvard Medical, Boston, six months Harvard University, five months Leiden, six months NCTR, Jefferson, AR and eight months Weizmann Institute. His topic of research is on “DNA structure, function, genotoxicity and metastasis”
Tumor cell lines have been established in our department to follow the pattern of metastasis formation in rats. Tumor progression could be traced reliably by orthotopic implantation of tumor cells in peritoneal (liver) and retroperitoneal (kidney) organs. Upon abdominal primary tumor formation, the tumor cell population exhibited markedly similar abilities characterized by: tumor cells originating from peripheral ruptures of blood vessels near the surface of the primary tumors were shed into the abdominal cavity; tumor cells released in the abdomen crossed the stomata of the diaphragm; tumor cells accumulated in thoracal, primarily in parathymic (internal mammary) lymph nodes and; after exhausting the defense capacity of the parathymic lymph nodes, the metastatic migration continued in the superior thoracal lymph node chain where the chyle returned to the vascular system. Colloidal carbon particles injected into the peritoneal cavity mimicked faithfully the migration of tumor cells. The direct lymphatic connection and migration of abdominal tumors cells to thoracal lymph nodes provided an explanation for the origin of thoracal and breast cancer metastasis. It is assumed that metastasis associated with the poor prognosis in breast cancer patients is related to the lack of knowledge of thoracal spread of tumor cells from abdominal primary tumors.
Craig Pierson earned his BSc in Zoology from the University of Canterbury, New Zealand. His work started with Ovine Linkage Mapping projects while at AgResearch in Dunedin and continued into genome sequencing while at Baylor College of Medicine in Houston. He has trained and supported customers in Sanger sequencing, qPCR, NGS, and gene expression applications while at Applied Biosystems, Illumina, HTG, VelaDx and ArcherDx. He joined the ArcherDX team as a Field Application Specialist in July, 2015.
Tumors within the same anatomic locations often show significant heterogeneity, exhibiting diverse mutation and gene expression profiles. Distinct cellular origins or microenvironments of tumor-initiating cells have both been shown to uniquely influence the development of specific driver mutations. For example, lung cancer subtypes that arise from different anatomic locations exhibit distinct mutation profiles. Furthermore, subtypes of Diffuse Large B-Cell Lymphoma (DLBCL) exhibit unique clinical behaviors and can be distinguished based on their cell-of-origin (COO), which can be identified based on the cells’ unique gene expression patterns. Therefore, identification of a tumor’s COO through gene expression profiling aids in the prediction of tumor behavior. Despite advances in next-generation sequencing (NGS) to detect mutations, these assays often cannot measure gene expression, leaving the COO elusive. Archer® FusionPlex® assays are based on Anchored Multiplex PCR (AMP™), a target enrichment strategy for NGS that uses molecular barcodes that enable the counting of unique molecules to assess differences of expression levels across target genes and between samples. This allows for simultaneous mutation detection and gene expression profiling to identify COOs. We analyzed expression patterns to predict the cellular origins of several 100 lung tumor FFPE samples by performing a principle components analysis on data generated by FusionPlex Comprehensive Thyroid Lung (CTL) NGS assays. Similarly, we identified DLBCL subtypes in a small cohort of samples using the FusionPlex Pan-Heme assay. These results show that AMP-based NGS, which is used to identify multiple mutation types, can also identify the cellular origins of tumors through gene expression profiling.
Michael Bilous studied Medicine at Cambridge and Birmingham Universities and completed his Pathology Training in New Zealand and Australia. He was the Head of the Tissue Pathology Department at Westmead Hospital until 2010. Currently, he is a Clinical Associate Professor at the University of Sydney and Conjoint Associate Professor at the University of Western Sydney. He has maintained a long standing interest in Breast and Gastrointestinal Pathology and written prolifi cally on breast and gastrointestinal pathology. He was a member of the Asia-Pacifi c task force and the 2013 ASCO/CAP update committee that published.
recommendations on HER2 testing in gastric and breast cancer, respectively.
Gastric cancer (GC) is the second most common malignancy aft er lung cancer and the third leading cause of death in Eastern Asia. As early gastric cancer is generally asymptomatic, patients oft en present with inoperable advanced or
metastatic disease. Importantly, the median survival time for patients with advanced or metastatic GC is less than a year. Given the above, exploring options that can help predict the prognosis and guide treatment of GC is of great importance. Human epidermal growth factor receptor 2 (HER2) overexpression has been correlated with poor outcome and a more aggressive
disease in patients with GC in several studies. Th e assessment of HER2 has also led to the development of targeted therapy for the treatment of GC with trastuzumab. Th e Trastuzumab for Gastric Cancer (ToGA) trial demonstrated that patients suffering from advanced GC with HER2 overexpression experienced an overall survival (OS) beyond one year following treatment with trastuzumab and chemotherapy. As HER2 is the only validated marker for predicting trastuzumab response, accurate detection of HER2 overexpression is essential. Enabling this, international recommendations for HER2 testing have been modifi ed to form APAC-specifi c HER2 testing guidelines. The guidelines contain recommendations that span the pre-analytic to postanalytic
stages of HER2 testing, emphasize the importance of multidisciplinary collaboration and account for the challenges of day-to-day testing faced by laboratories in APAC.
University of Malaya, Malaysia
Thamil Selvee Ramasamy earned her PhD in Clinical Medicine Research Programme from Imperial College London, UK. Currently, she serves as the Head of Cell & Molecular Biology Laboratory, Central Research Facility and as a Senior Lecturer at the Department of Molecular Medicine, Faculty of Medicine, University of Malaya. She has been actively engaged in stem cell research for a decade now and been invited to present the research findings in many national/international meetings. Currently, she also serves as the President of Tissue Engineering and Regenerative Medicine Society of Malaysia. She acts as a Sub-editor and Peer-Reviewer of a number of academic journals.
Hepatocellular carcinoma remains one of the most prevalent malignancies worldwide with chemoresistance and recurrence being the major hurdles leading to the failure of conventional anti-cancer treatment. Acquired resistance and metastasis are the two key challenges thought to be caused by cancer stem cells (CSC), a sub-population of cancer cells with stem cell properties, which are enriched upon conventional chemo- or radio-therapy. Numerous lines of evidence unravel the molecular mechanism undelying differential phenotypic behaviour of CSC, importantly; (1) the stem cell related signaling pathways, including Wnt/β-catenin, Sonic Hedgehog, Notch and PI3K/Akt/mTOR, (2) microRNA and epigenetics (3) the epithelial-mesenchymal transition and (4) evading from the immune system. Acquisition of these properties masking CSCs from being targeted by anti-cancer agents. Therefore, development of new strategies and discovery of inhibitors/lead compounds to enhance the chemosensitisation in CSC via reversal of EMT, modulation of critical regulators such as signaling pathways, microRNA and epigenetics, have the potential to be developed as an adjuvant anti-cancer treatment modalitites. The current effort are channeled towads the development and furmulation of these molecules using nanotechnology approaches to overcome the pharmacokinetic and pharmacodynamic drawbacks in order to develop an effective and targeted therapy for eradicating cancer.
Kasturba Medical College, India
Sumitha S has completed her MBBS from KMC, Manipal University and currently pursuing her internship in Kasturba Medical College and Hospital, Mangalore, Karnataka, India. She has been a part of various research works under different departments and participated in medical conferences held across India.
Supportive care includes those activities that ease the symptoms or the side effects of treatment. Research show that cancer patients are satisfied with clinical aspects of their care but they are dissatisfied with the information received about the disease, treatment and their side. The objective was to assess the supportive care needs of cancer patients under the following heads: Psychological; health system and information; physical and daily living and; patient care and support. A questionnaire based cross-sectional study (sample size=154) was done. Study tool used was supportive care needs survey short form-31 (SCNS-SF31) in the preferred language. Study population was cancer patients, above 18 years of age, diagnosed at least three months prior to the study. The collected data was analyzed using SPSS version 12 and mean scores along with standard deviations were expressed for each domain. Student independent test was used to know the observed difference between means across groups was statistically significant (‘p’<0.05). Out of 154 cancer patients, majority were females (88). Psychological needs of majority of cancer patients were met. There were unmet physical and daily living needs like handling the pain and tiredness with females having higher needs than males. Patients were found to have unmet needs in patient care and support domain, felt that the hospital staff were not empathetic (63.6%), and did not reassure that the way they feel is normal. Patients had unmet needs in getting information regarding tests (48.1%), benefits and side effects of treatment (49.4%), things to do to help themselves to get well (66.2%). This study will help doctors and hospital staff to address the felt needs of the cancer patients. Assessing the supportive care needs helps the caregivers to plan their supportive care according to the patient’s needs.
University Paris Descartes, France
Balaya Vincent is resident of Obstetrics/Gynecology in the Departement of Gynecological, Oncological and Breast Surgery at Georges Pompidou European Hospital in Paris and researcher at the Human Anatomy Department at University Paris Descartes.
Objectives: To review the characteristic ultrasound features of primary fallopian tube carcinoma (PFTC) and its relationship to the clinical history in order to establish specific findings useful for the preoperative diagnosis.
Method: An extensive review of the current literature was done on Medline via PubMed by using the following key-words: Primary Fallopian tube cancer , tubal cancer, adnexal malignancy mass, and ultrasound.
Results: PFTC corresponds to a complex, sausage shaped structures or cystic adnexal masses. A thick and an irregular capsule is in favour of a malignant lesion. Three-dimensionnal ultrasound is superior to 2-D ultrasound for the detection of tubal wall irregularities such as papillary projections or pseudosepta who were suggestive of tubal malignancy and allows a better assessment of the extent of tumor infiltration through the capsule. Neovascularization with low resistance indices are typical of tubal malignancy. Three-dimensionnal power Doppler sonography accurely detected structural abnormalities of the malignant tumor vessels which are randomly dispersed within the papillary projections. Intra uterine collection and peritumoral fluid are often finded but ascite could be also an indirect proof of peritoneal carcinosis.
Wayne State University, USA
Fazlul D Sarkar has completed his PhD from Banaras Hindu University and continued Post-doctoral studies at Memorial Sloan-Kettering Cancer Institute in New York. He has published 555 peer-reviewed research articles and review articles, and also published 50 book chapters. He edited four books and he is an Academic Editor for PLoS One, and also serves on the editorial board of 10 cancer journals. His basic science research led to drug discovery and he is an expert in conducting translational research including clinical trials.
Background: Th e combined annual mortality from pancreatic cancer (PC) and colon cancer (CC) is estimated to 88,170 deaths which surpasses the toll from breast and prostate cancer combined (72,280 deaths), and it represents the second leading cause of death aft er lung cancer (157,300 deaths), with no cure in sight, which is in part due to both intrinsic (de novo) and extrinsic (acquired) resistance to conventional therapeutics. Th is disappointing outcome is in part due to our inability to kill cancer cells that have undergone the Epithelial-to-Mesenchymal Transition (EMT) reminiscent of cancer stem/stem-like cells
(CSCs) which are resistant to conventional therapeutics. The aggressiveness of PC, and recurrence of CC (aff ects nearly 50% of patients treated by conventional therapeutics), is in part due to the re-emergence of chemotherapy-resistant CSCs. If these cells are the “root” of treatment failure, then elucidation of their intracellular signaling processes and discovering ways to target those events would be of immense importance for overcoming drug resistance especially by killing those resistant cells.
Methods: Our working hypothesis was that treatment failure in PC and CC is primarily due to therapeutic resistance contributed by the presence or enrichment of EMT-phenotype cells or CSCs, which must be eliminated to eradicate tumor and prevent tumor recurrence. We tested our hypothesis in preclinical (in vitro and in vivo) studies using both PC and CC cells by investigating whether our newly developed small molecule CDF, derived from a natural agentcurcumin, could be useful in killing drug resistant cells. We also investigated whether specifi c microRNAs (miRNAs) may in part be responsible for the killing of drug resistant cells by CDF alone or in combination with conventional therapeutics.
Results: We found that CDF could up-regulate the expression of miR-200 (low expression is the “hallmark” of CSCs and drug resistance) and reduced the expression of miR-21 (high expression is the “hallmark” of CSCs and drug resistance associated with tumor aggressiveness) in gemcitabine-resistant PC cells. Down regulation of miR-21 by CDF resulted in the induction of PTEN, an endogenous negative regulator Akt signaling. We also found decreased expression of EZH2 and increased expression of a panel of tumor-suppressive miRNAs (let-7a, b, c, d, miR-26a, miR-101, miR-146a, and miR-200b, c that are typically lost in PC) by CDF. Mechanistic investigation showed that the re-expression of miR-101 by CDF led to decreased expression of EZH2
and the killing of CSCs. We also found that CDF in combination with 5-fl uorouracil and oxaliplatin (5-FU + Ox) were able to kill the CSCs derived from CC cells. Moreover, we found that the expression of miR-34a and miR-34c was down-regulated in CC specimens compared to normal colonic mucosa and the loss of expression was consistent with data from CC cell lines.
Conclusions: Our results suggest that deregulation of miRNAs and their targets by CDF is mechanistically associated with overcoming drug resistance in both PC and CC. Moreover, CDF could become a novel demethylating agent for restoring the expression of miR-34 family and potentially other miRNAs, and thus CDF could become a newer therapeutic agent for the treatment of both PC and CC, which could be largely due to the killing of CSCs, resulting in overcoming drug resistance and tumor recurrence.
University of Jordan, Jordan
Malek Zihlif has completed his PhD from University of New South Wales, Post-doctoral studies from Stanford University School of Medicine. He is the Head of Pharmacology department at the School of Medicine, University of Jordan. He has published more than 25 papers in reputed journals. His research focuses on “How cells adapt to different condition and how cells overcome harsh condition such as hypoxia and drug assault”.
Hypoxia is a feature of most tumors and consider as a negative prognostic and predictive factor because of its role in the chemoresistance, radioresistance, angiogenesis, invasiveness, metastasis and resistance to cell death. Around 40% of all breast cancer and half of the locally advanced breast cancers include regions aff ected by hypoxia. Th is study was designed to simulate real hypoxic conditions as much as possible with the aim of characterizing the gene expression changes in metabolic and hypoxic related genes in response to long term hypoxia in MCF7 breast cancer cell line. Th e MCF7 breast cancer cells
were exposed to hypoxia episodes (1% oxygen) in two diff erent patterns. Th e fi rst was to expose the cells to 8 hours of hypoxia every other day with a total of 60 eposides and the second was to expose the cells to 72 hours of hypoxia every week for a total of 20 weeks. RNA was extracted at diff erent intervals in the two patterns and gene expression level was determined for the targeted genes. Regarding the hypoxic pathway genes, marked changes were identifi ed aft er both patterns of hypoxia. Half of the genes (12 genes) that shown remarkable changes were common to both conditions. Th ose common genes include the insulin-like growth factor binding protein 3, tumor protein p53 and endothelin-1. However, there was a very interesting observation regarding the gene expression of a gene called the hepatocyte nuclear factor 4, alpha (HNF4A) gene that was the most up-regulated genes in both cases scoring 32 folds aft er 60 hypoxic shots and 14 folds aft er 10 shots of 72 hypoxic shots.
Such changes in HNF4 were confi rmed using western blotting. Regarding the metabolic pathway changes, again some changes were observed giving a clear indication for switch from using glucose pathway as a scours of power toward using a diff erent pathway called pentose phosphate pathway. In conclusion, a collective gene expression data on diff erent long term hypoxic pattern fi rstly proposed HNF4A as a potential biomarker in tumor hypoxia and a major player in MCF7 breast cancer cell response to chronic hypoxia and secondly, indicate a switch in the normal metabolic pathway toward a new adapted pentose
Universiti Putra Malaysia, Malaysia
Zubaida Hassan has completed her MSc in the year 2015 from Universiti Putra Malaysia. She has published two papers in reputed journals and attended conferences and workshops. She is now an Academic Staff of the Department of Microbiology, School of Pure and Applied Sciences, Modibbo Adama University of Technology, Yola, Nigeria.
The pharmacological and/or biological activity of organic molecules isolated from plants or microbes can be used to treat human diseases. In this review, the anticancer effects of plant based and biotherapy has been compared. Traditional medicine systems in most countries were formed on plant-based natural products. The compound 1-(2,6-dihydroxy-4-methoxyphenyl)-2-(4-hydroxyphenyl) ethanone (DMHE) isolated from the ethyl acetate fraction of the Phaleria macrocarpa (Scheff.) Boerl fruit was found to cause a significant decrease in cell proliferation in HT-29 cells in a dose- and time-dependent manner after a 72 h treatment primarily due to necrosis. In another studies the potential anti-cancer activity of the Saussurea involucrata extract against hepatic cancer in vitro and its partial molecular mechanisms of activities were investigated. The results demonstrated that the extract has strong anti-cancer activity against liver cancer without significant effect on normal cells. However, probiotics known to boost human immune system are now been studied for anticancer properties through apoptosis. Interested to note is that probiotics found in human breast milk (E. faecalis and S. hominis) were able to cause significant decrease in MCF-7 (up to 33.29%) cell proliferation with no significant difference between the treated and the untreated MCF-10A cell line (>90% viability). Similarly, Lactococcus lactis spp lactis induced a strong anti-proliferative activity through S-phase accumulation in SNUC2A cells. Since apoptosis mechanism of cancer cell death is vital in chemotherapy-induced tumor cell death, biotherapy may be more comfortable supplement and future alternative to the current chemotherapy compared to the plant base therapies.
Pontifical Catholic University of Chile, Chile
Mauricio Camus A is a Breast Surgeon, Associate Professor, and Chief of the Department of Surgical Oncology, Pontificia Universidad Católica de Chile. He is the President of Chilean Society of Mastology during 2014-2016; President of Federation of Cancerology Societies of South America (2012-2014); Vice-president Chilean Society of Surgeons (2010-2012); President Chilean Society of Cancerology (2008-2010). He is an active member of the Board of the Senologic International Society and President of the Scientific Committee of the Latin American Federation of Mastology. He has published 18 papers in reputed international journals and 35 papers in Chilean journals. He has been serving as an Editorial Board Member of 2 repute journals.
Introduction: Although breast conserving treatment (BCT) has been standard practice for more than 20 years, there was no
consensus on what constitutes an optimal negative margin width, until the last 2 years.
Objective: To review the Consensus Guidelines on Margins for BCT with whole-breast irradiation in DCIS and in Stages I and II invasive breast cancer.
Material & Methods: A multidisciplinary consensus panel used a meta-analysis of margin width and ipsilateral breast tumor recurrence (IBTR) from a systematic review of 33 studies including 28,162 patients for invasive breast cancer and a review of 20 studies including 7,883 patients for DCIS.
Results: Positive margins (ink on invasive carcinoma or ductal carcinoma in situ) are associated with a 2-fold increase in the risk of IBTR compared with negative margins. For invasive breast cancer, negative margins (no ink on tumor) optimize IBTR.
Wider margins widths do not significantly lower this risk. Th e routine practice to obtain wider negative margin widths than ink on tumoris not indicated. For DCIS, a 2-mm margin minimizes the risk of IBTR compared with smaller negative margins. More widely clear margins do not significantly decrease IBTR compared with 2-mm margins.
Conclusions: Th e use of no ink on tumor is the standard for an adequate margin in invasive cancer. A 2-mm margin is the standard for an adequate margin in DCIS. Clinical judgment should be used in determining the need for further surgery in DCIS patients with negative margins narrower than 2-mm. Both consensus guidelines have the potential to decrease reexcision
rates, improve cosmetic outcomes, and decrease health care costs.