E-mail: oncology2017@scientificfuture.com | USA : +1-646-828-7579, UK : +44-203-695-1242 | April 05-07, 2017, Barcelona, Spain  


Keynote Speakers

Cancer Cell Biology

Session Introduction

Lu-Hai Wang
National Health Research Institute, Taiwan
Title: The Novel Role of CD24/Src Axis in Lymph Node Metastasis of Triple-Negative Breast Cancer (TNBC) and its application as a therapeutic target.


Abstract: To address how breast cancer cells interact with their surrounding microenvironment and successfully colonize at metastatic sites, we have established lung metastases-derived sublines from the MDA-MB-231 human breast cancer line using an orthotopic xenograft mouse model. Among the sublines, we identified a subline called LC with both lung and lymph node metastatic ability and another subline called IV2 with very high lung metastatic ability. We compared the global gene expression as well as EMT and cancer stem cell-related genes among parental MDA-MB-231, LC and IV2 cells. We selected a group of cell membrane bound ligand/receptor genes for initial analysis with respect to cell migration, invasion and anchorage independent growth. Among the genes examined, we found depletion of CD24 greatly impaired cell proliferation, migration/invasion and anchorage-independent growth (AIG). Depletion of CD24 reduced Src/MEK1/2 phosphorylation and suppressed downstream VEGF-A and VEGF-C expression in CD24-positive triple negative breast cancer cells (TNBC). Moreover, inhibition of CD24 reduced VEGF-induced migration of HUVEC and lymphatic endothelial cells. Treatment of the cells with CD24 monoclonal antibody (mAb) greatly impaired migration/invasion and AIG of LC cells and other CD24-expressing TNBC cells. Tail vein injection mouse model showed that CD24-depleted cells were impaired in targeting to lung and displayed greatly reduced lung colonization ability. Orthotopic xenograft mouse model showed that CD24-depleted cells grew smaller tumors, which had reduced angiogenesis and lymphangiogenesis. Depletion of CD24 effectively inhibited lymph node as well as distant organs metastasis including lung and bone, suggesting that CD24 is essential for breast cancer cell metastasis. Using CD24 Mab, we showed perturbation of cell surface CD24 reduced breast cancer lymph node and lung metastasis. Clinically, Kaplan Meier survival analysis using several public databases revealed that high expression of CD24 significantly correlated with poor survival and earlier recurrence. Moreover, high level of CD24 specifically correlated with basal-like subtype (triple negative) and luminal subtype but not with HER2+ subtypes of breast cancer. Collectively, we have shown that CD24/Src signaling is crucial for primary tumor growth, lymph node and other distant organ metastasis of breast cancer. Therefore, perturbation of CD24 including using mAb could serve as a promising therapeutic approach for intervening breast cancer metastasis.

Yvonne Tay
National University of Singapore, Singapore
Title: MicroRNA-638 regulates iron storage in prostate cancer via a gene:pseudogene network

Biography: Yvonne began her research career in Bing Lim’s lab at the Genome Institute of Singapore, supported by an A*STAR Graduate Scholarship, and her PhD work led to key insights into the scope and mechanisms of microRNA activity (Miranda et al, Cell 2006; Tay et al, Nature 2008). Subsequently, she pursued her postdoctoral training in Pier Paolo Pandolfi’s lab at Harvard Medical School and Beth Israel Deaconess Medical Center under a Special Fellow award from the Leukemia & Lymphoma Society, and this research led to the discovery that protein-coding transcripts can co-regulate the tumor suppressor PTEN by competing for shared microRNAs (Tay et al, Cell 2011; Karreth et al, Cell 2011). Yvonne has recently returned to Singapore to begin her independent research career, and has been awarded the Singapore National Research Foundation Fellowship and NUS President’s Assistant Professorship to continue her research into this previously uncharacterized layer of gene regulation.

Abstract: Iron is an essential metal, known to play critical roles in various cellular processes. Studies have demonstrated the detrimental effects of tilting the systemic iron balance that could lead to various human pathologies. It is becoming increasingly clear that perturbation of iron homeostasis is linked to tumorigenesis. However, little is known about microRNAs (miRNAs) in the regulation of iron metabolism. MiRNAs belong to a class of small non-coding RNAs that acts as important post-transcriptional modulators of key genes in multiple biological pathways. Aberrant expression of miRNA could result in the deregulation of tumor suppressors and/or oncogenes to initiate carcinogenesis. In this study, we characterize miR-638 as a crucial player in iron metabolism in prostate cancer. MiR-638 targets ferritin heavy chain, FTH1, and several of its pseudogenes. We find that overexpression of miR-638 downregulates these targets and promotes tumor growth, suggesting the involvement of a ceRNA network in the tightly regulated iron metabolism pathway and the potential role of its disruption in prostate cancer development.

Adam Marcus
Emory University, USA
Title: "Image-guided genomics of phenotypically heterogeneous populations reveals vascular signaling during symbiotic collective cancer invasion"

Biography: In 2006, Dr. Marcus became an Assistant Professor at the Winship Cancer Institute and developed his own laboratory which focuses on cell biology and pharmacology in lung and breast cancer. Dr. Marcus was named a Georgia Cancer Coalition Scholar. He is Director of the Emory Integrated Cell Imaging Core (ICI), a jointly managed shared resource of the Winship Cancer Institute and Emory University School of Medicine. The ICI provides cellular imaging technology, services, and expertise to support the research initiatives of the Winship Cancer Institute. Dr. Marcus also directs an educational outreach program Students for Science with the goal of providing science, technology, engineering, and mathematics (STEM). Dr. Marcus' laboratory has been funded by the NCI, NCCAM, ACS, and private donations. Dr. Adam received his PhD in Biology from Penn State University in 2002 and went on to do a post-doctoral fellowship in cancer pharmacology at Emory University in the laboratory of Dr. Paraskevi Giannakakou from 2002 to 2004.

Abstract: To probe the phenotypic heterogeneity found in cell populations, we developed an image-guided genomics technique termed spatiotemporal genomic and cellular analysis (SaGA) that allows for precise selection and amplification of living and rare cells. SaGA was used on collectively invading 3-D cancer cell packs to create purified leader and follower cell lines. The leader cell cultures are phenotypically stable and highly invasive in contrast to follower cultures, which show phenotypic plasticity over time and minimally invade. Genomic and molecular interrogation reveals an atypical VEGF-based vasculogenesis signaling that facilitates recruitment of follower cells but not for leader cell motility itself, which instead utilizes focal adhesion kinase-fibronectin signaling. While leader cells provide an escape mechanism for followers, follower cells in turn provide leaders with increased growth and survival. These data support a symbiotic model of collective invasion where different phenotypic cell types cooperate to promote their escape.

Padmaa Paarakh
The Oxford College of Pharmacy, Karnataka, India
Title: IN VITRO AND IN SILICO ANTICANCER ACTIVITY OF Negundoside isolated from leaves of Vitex negundo Linn


Abstract: Vitex negundo Linn.[ Verbenaceae], commonly known as Five-leaved Chaste tree or Monk’s Pepper (Hindi —Sambhalu, Nirgundi) is used as medicine fairly throughout the greater part of India. To isolate negundoside and evaluate anticancer activity by in vitro and in silico method. Negundoside was isolated by column chromatography from ethyl acetate fractionation of methanol extract of leaves of V.negundo. Negundoside was characterized by UV,IR, 1H-NMR, 13C-NMR and Mass spectrum. Standardization of negundoside was done by HPTLC fingerprinting. In vitro anticancer activity was done using HeLa cell lines by MTT assay at different concentrations ranging from 20-100 µg/ml and in silico docking studies using enzyme EGFR tyrosine kinase. Fingerprinting of isolated negundoside were done by HPTLC method.The IC50 value was found to be 62.69 µg/ml in in vitro anticancer activity in HeLa Cell lines. Negundoside was subjected to molecular docking studies for the inhibition of the enzyme EGFR tyrosine kinase, which is one of the targets for inhibition of cancer cells. It has shown -7.32 kJ mol-1 binding and -11.32 kJ mol-1 docking energy with five hydrogen bonds. Negundoside has shown to possess anticancer activity both in vitro and in silico studies.

Cancer Therapies

Session Introduction

Celine Cano
New Castle University, UK
Title: Development of potent inhibitors of the DNA-dependent protein kinase (DNA-PK)

Biography: Celine studied Organic Chemistry at the University of Poitiers (France) where she received her Ph.D. degree in 2004 for research on the synthesis of biomolecules by 1,3-dipolar cycloadditions with carbohydrates. From 2004-5, she carried out post-doctoral work in the group of Professor John A. Joule at the University of Manchester working on the synthesis of analogues of cofactors of oxomolybdoenzymes. In November 2005 she joined the Northern Institute for Cancer Research at Newcastle University as a research associate, working along Professors Roger Griffin and Bernard Golding on the synthesis of inhibitors of DNA-dependent protein kinase (DNA-PK). She was appointed to a lectureship at Newcastle in 2008, promoted to senior lectureship in 2013, and has since played a key role in helping to establish Newcastle as an internationally recognised centre for anti-cancer drug development.

Abstract: The cellular response to DNA double-strand break (DSB) formation is an essential component of normal cell survival, following exposure to DNA-damaging chemicals (e.g. cisplatin and doxorubicin) and ionising radiation [1]. The serine/threonine kinase DNA-dependent protein kinase (DNA-PK) is a member of the phosphatidylinositol (PI) 3-kinase related kinase (PIKK) family of enzymes, and plays an important role in DNA DSB repair via the non-homologous end-joining (NHEJ) pathway [2]. DNA-PK inhibitors may, therefore, be useful as agents to improve the activity of radio- and chemo-therapy in the treatment of cancer [3]. Identification of the lead benzo[h]chromen-4-one DNA-PK inhibitor NU7026 (IC50 = 0.23 uM), guided the subsequent development of the potent and selective ATP-competitive chromenone NU7441 (DNA-PK IC50 = 30 nM) [4]. Although proof-of-principle studies with NU7441 confirmed promising activity in vitro as a chemo- and radio-potentiator in a range of human tumour cell lines [5], further biological studies with NU7441 were hampered by sub-optimal pharmaceutical properties. In collaboration with AstraZeneca Pharmaceuticals, structure-activity relationship studies for DNA-PK inhibition by chromenone-derivatives were conducted in conjunction with homology modelling. This approach predicted several positions on the pendant dibenzothiophen-4-yl substituent of NU7441 as tolerant to substitution, without detriment to DNA-PK inhibitory activity. We will describe the rational design and syntheses of analogues that optimised the physicochemical and pharmacokinetic properties of NU7441. These studies resulted in the identification of compounds that combined potent DNA-PK inhibition with excellent aqueous solubility (20-40 mg/mL as acid salts), without compromising cellular activity. Prominent amongst these derivatives is KU-0060648 (DNA-PK IC50 = 8.6 nM), which exhibits 20-1000 fold selectivity for DNA-PK over related PIKK enzymes and PI3K family members. The discovery and further development of KU-0060648 and analogues will be described, including in vivo efficacy and combination studies [6-8].

Animesh Dhar
University of Kansas Medical Centre, USA
Title: Novel inhibitor GZ17-06.02 suppresses pancreatic cancer tumorigenesis through inhibition of sonic hedgehog signaling pathway

Biography: Dr. Dhar completed his PhD from University of Calcutta in Physiology and did his post-doctoral training in University of Puerto Rico in Biochemistry and University of Missouri-Columbia in Pharmacology. Then, Dr. Dhar became Research Track Assistant Professor in Pharmacology, University of Missouri-Columbia and then moved to University of Missouri-Kansas City School of Medicine as Associate Professor. He joined in the Department of Cancer Biology as an Associate Professor in University of Kansas Medical Center. Dr. Dhar has published more than 60 publications in the journals of international repute and about more than 10 reviews in the area of his research

Abstract: Purpose: Pancreatic ductal adenocarcinoma (PDAC) or pancreatic cancer is one of the most lethal malignancies in humans. The survival rate for two years is very limited in most of cases (10%) after diagnosis of this disease. Novel therapeutic targets are needed to treat this disease because nothing is available in PDAC. GZ17-06.02 contains a nutraceutical for its anti-cancer properties, in several cancers. Crude extracts of the plant Arum palaestinum Boiss used in traditional Israeli and Palestinian medicine, have demonstrated cytostatic and cytotoxic activities in colon, prostrate and lung carcinoma. Therefore, we hypothesize that GZ17-06.02 will inhibit tumor progression and metastasis in PDAC by suppressing cancer stem cells (CSC) and sonic hedgehog (SHH) pathway. Experimental Procedure: In this study, we have determined cell proliferation, pancosphere formation and apoptosis following treatment of different doses of GZ17-06.02 for 24-72 hours using MiaPaCa-2 and S2-007 human pancreatic cancer cells. Cell cycle distribution and apoptosis were measured using flow cytometic analysis. Orthotopic pancreatic cancer model in athymic mice was developed and GZ17-06.02 was given orally for 20 days to those mice. Proliferative markers, pEGFR/pAkt and apoptotic markers, Bax/Bcl-2, were monitored following treatment with GZ17-06.02 in both in vivo and in vitro models. Metastatic markers, MMP-2 and MMP-9 were measured in metastatic tissues in orthotopic models. SHH pathway was determined using western blot, immunohistochemistry and cellular thermal shift assay (CETSA). Results: GZ17-06.02 inhibited proliferation and stimulated apoptosis of pancreatic cancer cell lines in a dose- and time-dependent manner. Moreover, the compound significantly inhibited epidermal growth factor receptor and Akt phosphorylation. Furthermore, GZ17-06.02 decreased the number and size of the pancospheres in S2-007 cells with concomitant inhibition of pancreatic cancer stem cell markers, DCLK1, Lgr5 and EpCam. SHH pathway significantly inhibited by GZ17-6.02 treatment. The effect of GZ17-06.02 suppressed tumor growth and metastatic potential as indicative of MMP-2 and MMP-9 activity in primary and metastatic tumors. Conclusions: GZ17-06.02 significantly reduces tumorigenesis and metastasis in both in vitro and in vivo pancreatic cancer models, by inhibiting CSC and SHH pathway. .

Thomas Kieber-Emmons
University of Arkansas for Medical Sciences, USA
Title: Inducing immune responses to tumor associated carbohydrate antigens by a carbohydrate mimetic peptide vaccine: clinical experience in Phase I and Phase II trials

Biography: Thomas Kieber-Emmons, PhD., is known for his work on developing peptide mimetics of carbohydrate antigens as vaccines. Dr. Kieber-Emmons received a PhD in Biophysics from the Roswell Park Cancer Institute/State University of New York at Buffalo, focusing on computational chemistry and biology. Dr. Kieber-Emmons did post-Doctoral studies in Molecular Immunology at Roswell Park focusing on the structural basis for molecular mimicry of antigens. He then moved to Idec Pharmaceuticals (now Biogen) where he was head of IDEC’s peptide therapeutics program and worked on anti-idiotypic vaccines for lymphoma. He was recruited in 1990 to the Wistar Institute and the University of Pennsylvania. Since 2002 he holds the Josetta Wilkins Chair in Breast Cancer Research at the Winthrop P. Rockefeller Cancer Institute at the University of Arkansas for Medical Sciences.

Abstract: We are developing an active vaccination strategy targeting tumor associated carbohydrate antigens (TACAs) using carbohydrate mimetic peptides (CMPs). TACA support cell survival that can be interrupted by anti-carbohydrate antibodies. An early-phase 3+3 clinical trial in breast cancer patients was conducted to evaluate the feasibility, safety and immune functionality of a CMP referred to as P10s, which can induce TACA reactive, proapoptotic antibodies. P10s was developed as a Pan immunogen, mimicking both the ganglioside GD2 and the neolactoseries antigen Lewis Y. A dose-escalation trial of the vaccine plus adjuvant was conducted in two cohorts of 3 subjects each. Patients were restricted to females of all races with histologically or cytologically confirmed stage IV breast cancer who had stable disease and a positive recall-antigen response. P10s was synthesized with the Pan-T-cell epitope PADRE and formulated at 300 and 500 μg/injection with MONTANIDE™ ISA 51VG for the 1st and 2nd cohorts, respectively. Doses of the vaccine were administered to research participants subcutaneously on weeks 1, 2, 3, 7 and 19. Blood samples were collected at various time points and tested for presence of proapoptotic antibodies. Binding of pre-immune and post-immune sera was assessed against breast cancer cell lines. The vaccine induced antibodies in all 6 subjects, displaying significant cytotoxic activity against several representative human breast-cancer cell lines. Vaccination generates IgG response with serum antibodies capable of inhibiting tumor growth in spheroid culture of breast cancer cell lines. Caspase 3 was involved in the postimmune serum-mediated apoptosis. Immunization with the P10s vaccine was found to be well-tolerated and induces functional antibodies that potentially have a cell death mediated therapeutic benefit. The data suggest that the vaccine-induced anti-tumor immune response in combination with standard of care chemotherapy may further improve clinical outcome. Consequently, we are testing the vaccine in a Phase II study in the neoadjuvant setting.

Sabahattin Comertpay
Kahramanmaras Sutcu Imam University, Turkey
Title: Investigation of in vitro Effect of Capsaicin on Normal, Immortalized and Cancerous Cells of Pleura: Preliminary Data

Biography: Author Assist. Prof. Dr. Sabahattin COMERTPAY was a chemistry-trained bachelor. Then, he received his MSc in Biochemistry by studying the insertion/deletion polymorphism of Antiogensin Converting Enzyme gene in patients with chronic hepatitis. Later, with the support of a scholarship provided by Ministry of National Education of Turkey, he studied molecular biology of pleural mesothelioma, in Cancer Research Center of Hawai, USA, for his PhD between the years of 2008 and 2012. He currently works in Sutcu Imam University, Kahramanmaras, Turkey where he, with his master and PhD students, investigates the efffect of capsaicin on mesothelial cells in his small yet effective laboratory.

Abstract: Malignant pleural mesothelioma (MPM), a type of cancer developed from the lining tissues of lung upon a prolonged exposure to asbestos and/or erionite, is a rare but a highly fatal disease [1]. In erionite-high villages of Central Anatolia, the disease, along with another type of mesothelioma developed in the membrane of stomach-perionetal mesothelioma, have been discovered to be responsible of 50% of the death [2]. Capsaicin, the pungent compound produced by various species of Capsicum genus, has been shown to eliminate cancer cells through apoptosis in vitro and in vivo [3]. In this TUBITAK (Turkish Scientific and Technological Research Council) funded study (Project No : 214 S 183), we treated commercially obtained cancerous (ATCC-5946), immortalized (Coriell Institute-AG07086) and normal cells (ZenBio-MESM012916B) of pleura with gradually increasing concentrations of synthetic capsaicin solved in ethanol, and IC50 values of the agent in 12 hours were determined via MTS Assay. As a result, we found that capsaicin in ethanol was more effective at inducing cell-death in cancerous cells (IC50: 300 µM) compared to in immortalized cells (IC50: 334 µM) and normal cells (IC50: 360 µM). Additionally, when similar experiments in 48 hours were repeated with capsaicin solved in DMSO, IC50 values were calculated as remarkably higher for the cancerous and immortalized cell lines (417 and 575 µM, respectively), indicating an increase in the amount of capsaicin required, which, overall, suggested that ethanol might be a better solvent for the therapeuatic purpose of capsaicin. In conclusion, our preliminary data imply that capsaicin solved in ethanol may have the potential to be used as a drug in elimination of MPM, which might not harm normal cells in appropiate concentrations. Nevetheless, our research is still ongoing to reveal the mechanism through which the cells have been eliminated by this compound.

Said Hilmani
Hassan II University, Casablanca, Morocco
Title: Prognosis factors of Medulloblastoma in Moroccan patients


Abstract: Background: Medulloblastoma is a primitive malignant embryonic tumor of the child. It represents 30% of those located in the posterior cerebral fossa. Our work is a retrospective analysis of a series of 60 cases of medulloblastoma taken care of at the neurosurgery department of the CHU IBN ROCHD in Casablanca between January 2006 and December 2013, the aim of which is to evaluate the therapeutic protocol and the prognostic factors. Methods : Mean age was 10.8 years, with a male predominance (sex ratio of 4.45). Symptomatology was dominated by intracranial hypertension associated with cerebellar syndrome (96.66% of cases). Cranial pairs were noted in 21.7%. The location was median in 66, 66% of cases and hemispherical in 20%. Hydrocephalus was noted in all patients. Total excision was performed in 73, 33% of patients. Radiotherapy was received by 86.66% of patients, with an average delay of 2 ½ months and chemotherapy by 91.66% of patients, with an average delay of 1.15 months. Results: The operative mortality was 8.33%. We found 3 cases of recurrence after an average delay of 6.33 months. Survival rate at 5 years was 70%. The factors influencing the prognosis (p <0.05) were age, quality of excision and complementary radio-chemotherapy. The sex, location and volume of tumor do not statistically influence survival. Discussion and conclusion: Prognosis of medulloblastomas is improving as a result of the progress made in neuroimaging and in neurosurgery allowing a fairly wide excision and new means in radio-chemotherapy. It also depends on early diagnosis and multidisciplinary.

Epidemiology and Prevention

Session Introduction

Srdjan Denic
United Arab Emirates University, UAE
Title: Breast cancer protection by parental consanguinity is explained by kinship theory of genomic imprinting

Biography: Srdjan Denic is a Professor of Medicine in the College of Medicine and Health Sciences, UAE University, Al Ain, UAE. He has completed oncology training in Mount Sinai Hospital, NY, and has worked in the University Hospital, SUNY, Syracuse, NY. His current research focus is on human consanguinity and its effect on common blood disorders and risk of malignancy.

Abstract: The effect of human inbreeding on breast cancer risk is unclear. Several studies have confirmed that parental consanguinity protects against breast cancer in Arabs. Newborns of consanguineous parents are smaller than newborns of non-consanguineous parents—newborn size is a well-known risk factor for breast cancer. Both smaller birth size and lower risk of breast cancer could be explained with the conflict of genes in baby. In the fetus, maternally and paternally derived developmental genes regulate cell proliferation and fetal growth. The expression of these genes determines the size of newborn including the number of its mammary stem cells from which breast cancer develops later in life. Thus, in smaller babies, as there are less mammary stem cells, the chance of their malignant transformation is lower than in bigger babies. The expression of developmental genes is regulated by imprinting (e.g., DNA methylation), which is triggered by environmental stimuli. One such stimulus is environment in which maternally and paternally derived gene duplication and propagation in future pregnancies is likely to be unequal. This causes conflict between parental genes in the fetus the mechanism of which is elucidated by the kinship theory of genomic imprinting. In general, when conflict is less intense, smaller babies are produced and vice versa. According to this theory, gene conflict is less in a baby whose mother is married to father’s brother’s son (FBS union) and some other types of close kin unions. The FBS marriages are most common type of consanguineous marriages in Arabs. Consequently, most consanguineous parents produce smaller babies who less often develop breast cancer later in life.

Sharmila Pimple
Tata Memorial Centre, India
Title: Prevalence of Human Papilloma Virus and Cervical Intraepithelial Neoplasia, among women living with HIV in Mumbai, India.

Biography: Dr Sharmila Pimple, M.D , is Professor in the Department of Preventive Oncology at the Tata Memorial Hospital, Mumbai. Her major interests and area of work involves Common cancer control, prevention and early detection . Dr. Pimple is also involved in developing, planning, implementation, monitoring and evaluation of sustainable population based cancer control and early detection programmes in the urban and rural community settings. Dr Pimple has successfully undertaken several International collaborative research trials and Intramural research projects in the capacity of Principal Investigator and Co Investigator on evaluating various low cost technologies for cervical, and oral cancer screening, including HPV Vaccine trials.

Abstract: BACKGROUND: HIV-related immunosuppression predisposes co-infection with Human Papillomavirus (HPV) and increases the risk of cervical intraepithelial neoplasia and cervical cancer. Centers for Disease Control (CDC) has included invasive cervical carcinoma among the AIDS-defining conditions. India shares 25% of global burden of cervical cancer and a large burden of HIV-infected women who currently continue to live longer due to improved access to antiretroviral Therapy. The current study estimates the prevalence of HPV and the risk of cervical pre-cancer and cancer among HIV positive women in Mumbai, India. METHODS: Retrospective analysis of 262 HIV Positive women attending cervical cancer screening services in a tertiary care centre between 2009-12 using Visual inspection with acetic acid (VIA), Pap cytology and HPV testing were included in the analysis. Diagnostic confirmation with Colposcopy with or without biopsy was considered as the gold standard for the diagnosis for cervical intraepithelial neoplasia (CIN) and invasive cancer. RESULTS: Screen positivity rate for cervical cancer screening by VIA and HPV DNA test was 34.7% and 35.9% respectively. Pap cytology reported 25(9.5%) cases of low grade squamous intraepithelial lesions (LSIL) and 15 (5.7%) cases of high grade squamous intraepithelial lesions (HSIL). Histopathology confirmed 20 (7.6%) cases of CIN 2 and above lesions in HIV positive women. CONCLUSIONS: The prevalence of HPV infection and CIN are significantly higher in the HIV-positive women in India and there is urgent need to integrate and provide access to adequate cervical cancer screening services in HIV testing and counseling centers in the country.

Sakshi Sharma
Roko Cancer Charitable Trust, India
Title: Prevention is better than cure- Cancer awareness and early detection is the key

Biography: Dr Sakshi Sharma, a public health professional grew up in New Delhi, India. She received a Bachelor’s degree in Dental Surgery and a Post-Graduate in Health Administration from the Apollo Group of Hospitals. After her graduation, the prodigious doctor got enthused to well-being and general healthcare of the masses which had her finding answers for the prevention rather than cure of diseases. Her quest for these answers led her to Roko Cancer Charitable Trust a renowned international not for profit organization headquartered in London and New Delhi. In her limited professional career she has travelled the length and breadth of India educating and creating awareness about the know’s and how’s of Cancer to nearly half a million general public ignorant of the life threatening disease. Her relentless effort in the field of cancer awareness and prevention has seen her raise over 200 million in Indian rupees to be utilized for the empowerment of cancer survivors, patients and the society in general.

Abstract: Cancer is one of the leading causes of morbidity and mortality worldwide, with approximately 14 million new cases in 20121. The number of new cases is expected to rise by about 70% over the next 2 decades. It is the second leading cause of death globally, and was responsible for 8.8 million deaths in 2015. Globally, nearly 1 in 6 deaths is due to cancer. Approximately 70% of deaths from cancer occur in low- and middle-income countries. Around one third of deaths from cancer are due to the 5 leading behavioural and dietary risks: high body mass index, low fruit and vegetable intake, lack of physical activity, tobacco use, and alcohol use. Tobacco use is the most important risk factor for cancer and is responsible for approximately 22% of cancer deaths.2. Cancer causing infections, such as hepatitis and human papilloma virus (HPV), are responsible for up to 25% of cancer cases in low- and middle-income countries3. Late-stage presentation and inaccessible diagnosis and treatment are common. The economic impact of cancer is significant and is increasing. The total annual economic cost of cancer in 2010 was estimated at approximately US$ 1.16 trillion4. Only 1 in 5 low- and middle-income countries have the necessary data to drive cancer policy5 A comprehensive solution can be achieved by first conducting mass awareness and early detection programmes and emphasis on relevance of self examination to make a lasting impact. There is a considerable role of Community engagement programmes to create a “Tier system effect” emphasizing on significance of educating of basic health line workers for health promotion to reach out to the community at large. Here lies the role of healthcare non-profit organizations in identifying and reaching the grassroots in developing countries like India. We must also know that at what level does the difference in myths and dogmas reside in educated and uneducated class of a developing nation and are we actually following a blind path. Timely detection plans are being run worldwide but spot on approach is to be followed along with emphasis on opportunistic and organized screening is the need of the hour. Much needed to full fill the target is having cohesive, holistic and collaborative opportunities and welcoming best practices from the west for awareness and early detection programmes and inviting the western healthcare stakeholders to help low/middle economic nation for the same. This shall help the world being focused at once for the common cause and the common healthcare improved strategies can be followed against the dreaded disease.

Valentina Drozd
The International fund “Help for patients with radiation-induced thyroid cancer “Arnica”, Minsk, Belarus
Title: Combined effects of nitrates in drinking water and radiation on the induction of thyroid cancer in Belarus after Chernobyl accident

Biography: Dr. Valentina is an author of more than 270 research papers and 7 monographs published in USA, Germany, Japan, Russia and Belarus. She has more than 30 years of research of medical issues related to the Chernobyl accident and radio induced Thyroid cancer. 08.2004 – present: International Fund “Help patients with radio induced thyroid cancer” Minsk, Belarus, Director 2007 - Present: Project Chernobyl, New-York, USA, Head of international department 2003 – Present: Belarussian Medical Academy for Postgraduate Education Minsk, Belarus, Professor of Endocrinology Department

Abstract: The incidence of pediatric thyroid cancer in Belarus increased dramatically after the Chernobyl accident. Moreover the incidence of thyroid cancer has been steadily increasing during the last 30 years worldwide most markedly in France, Italy, the Republic of Korea, Australia and the United State. Thyroid cancer incidence is increasing more rapidly than any other malignancy. The main factors contributing to this increase continue to be debated. Based on ecological data, considering metabolism of nitrate, and biological plausibility, we suggest that nitrate pollution may modify the radiation related risk of thyroid cancer contributing to regional differences in rates of thyroid cancer. Analysis of the environmental situation in Belarus showed that in rural areas the population is using drinking water from open wells with high levels of nitrate contamination exceeding the Maximum Contaminated Level by 2.5 and 4.0 times. The experience of studying pediatric radiation induced thyroid cancer in Belarus after the Chernobyl accident has shown that radiation dose was significantly associated with thyroid cancer incidence (P=0.029). Effect of radiation significantly varied according to nitrate concentration in drinking water (P=0.004). We found significantly higher prevalence rates of thyroid cancer among rural residents compared with urban in Gomel, Mogilev, Brest oblasts - most contaminated areas with higher thyroid doses (P<0,001). There was no difference in prevalence rates of thyroid cancer in other oblasts (Minsk, Grodno, Vitebsk). We do not find statistical difference between the thyroid cancer incidence in rural and urban residence of all oblasts in children who were born after the Chernobyl disaster. Studies of the combined influence of radiation and nitrates exposure will give us a better understanding of increases in the incidence of thyroid cancer, particularly papillary carcinoma, in many countries over the past 30 or so years.

Diagnosis and Therapy

Session Introduction

Nira Ben-Jonathan
University of Cincinnati Cancer Institute, USA
Title: Dopamine receptor-1 in breast cancer: Expression, signaling and targeting


Abstract: The basic theoretical question asked was : why should cancer cells invent ‘de novo’ new and unique immune escape mechanisms (during each single and different human carcinogenesis process) if they might “simply” use (or partially ectopically express) intrinsic immune escape gene programs naturally developed during mammalian evolution over millions of years to allow for materno-fetal immune tolerance? Genomic analysis (Nanostring Inc, Seattle, WA, USA) was carried out in primary breast cancer with metastatic homolateral axillary lymph nodes as well as placenta tissue (both uterine decidual tissue and term placenta tissue) from a pregnant woman (same patient). Gene expression profiling of paired non-self and self tissues (i.e. placenta/uterus; breast cancer/normal breast tissue; metastatic lymphnode/normal lymphnode tissue) was performed using the PanCancer Immune gene panel, a 770 Nanostring gene expression panel. Our findings reveal overlapping in specific immune gene expression in placenta and cancer tissue, suggesting that these genes might play an important role in maintaining immune tolerance both physiologically (in the placenta) and pathologically (in the cancer setting). Placenta and uterus, breast tissues (tumor and normal) and lymph node tissues (tumor and normal) formed their own RNA transciption cluster, suggesting that tissue specific gene expression patterns were well preserved during experimental procedures and that tissue specific expression pattern overshadows gene expression differences within each tissue type. We then analyzed differential expression within each tissue type (i.e. matching for the analysis placenta with uterus, breast cancer with normal breast tissue and node positive with node negative tissue). Among the 583 genes analyzed, 103 genes were upregulated > 1.5 fold in placenta versus uterus, while 258 genes were downregulated at least 1.5 fold. Using the same cut-off, 258 genes were upregulated and 44 genes downregulated in breast tumor versus normal breast tissue, and 178 genes were upregulated while 146 genes downregulated in tumor bearing lymph node versus non-involved lymph node.

Alain R. Thierry
INSERM, France
Title: Circulating DNA analysis as the next generation diagnostic in oncology

Biography: A.R. Thierry is Director of Research at the INSERM in the Institute of Research of Cancerology of Montpellier, France. His research interest focuses on the study of the diagnostic capacity of circulating DNA and the development of methods towards supporting personalised medicine. A.R. Thierry has coordinated a prospective blinded multicentric studies showing the first clinical validation and demonstration of clinical utility of the plasma DNA analysis in oncology, by detecting point mutations in KRAS and BRAF from colorectal patients. He is one of the world leaders in the clinical application of the analysis of circulating DNA and now he is directing various studies on prognosis, cancer patient follow up and cancer screening. He is the principal founder of DiaDx, a Biotech company devoted to liquid biopsy solutions in oncology.

Abstract: Circulating cell-free DNA (cfDNA) analysis constitutes a hopeful approach to provide a non-invasive tumor molecular test for cancer patients from a simple blood test. Based upon basic research on the origin and structure of cfDNA, new information on circulating cell-free DNA (cfDNA) structure and specific determination of cfDNA fragmentation and size, we revisited Q-PCR based method and recently developed the Allele Specific-Q-PCR based-method with blocker (termed as Intplex) which is the first multiplexed test for cfDNA. The Intplex test can be adapted to all mutations, genes or cancers and enables rapid, highly sensitive, cost effective and repetitive analysis. It offers the opportunity in detecting quantitatively and dynamically mutation and could constitute a non-invasive attractive tool potentially allowing diagnosis, prognosis, theranostics, therapeutic monitoring and follow-up of cancer patients expanding the scope of personalized cancer medicine. We carried out two clinical studies in metastatic colorectal cancer patients (i) the clinical real-time evaluation of circulating tumor DNA (ctDNA) analysis for detecting point mutations in comparison with tumor tissue analysis before initiation of anti-EGFR therapy and (ii), the study of the emergence of associated resistance mutation in refractory patients under treatment. (i) We realized a real-time blinded prospective multicentric clinical study on 140 patients comparing KRAS (exon 2,3 and 4), NRAS (exon é and 3) and BRAF V600E mutations determination by plasma and tissue analysis carried out in the conditions of standard management care. On 121 patients where both analysis were made, 43% were found mutant by tumor tissue analysis while 57% were found KRAS mutant by ctDNA analysis. 7.2% of patients were found BRAF mutant by tumor tissue while 14.4% were determined mutant by ctDNA analysis. 13% of plasma samples carried multiple KRAS point mutations and 4% of plasma samples exhibited at least one KRAS point mutation combined to the presence of BRAFV600E point mutation. Median data turnaround time was 16 [3-273] days for tumor tissue while it was 2 [0.5-10] days for ctDNA analysis. Extensive analysis of discordant samples revealed that use of biopsy, delay between tumor tissue specimen collection and blood draw, and absence of primary tumor at time of blood draw are the main clinical and technical factors potentially affecting concordance. In addition, most of the samples scored mutant by plasma while being tested WT by tumor tissue analysis seem clinically relevant in respect to the anti-EGFR resistance (RAS status) and to the overall survival (BRAF status). By way of observed higher level of mutation frequencies, plasma analysis appears more accurate than tissue analysis consistent with the intra-tumor or inter-tumor heterogeneity and the clonal evolution dynamics. Lastly, we present the first distribution profile of the RAS and BRAF hotspot mutations in non-stratified mCRC patients. Altogether, this is the first initial report stringently demonstrating the clinical utility of using ctDNA analysis for testing the actionable hotspot mutations in a large cohort of mCRC patients. (ii) In the other blinded clinical study, we retrospectively analyzed RAS (KRAS and NRAS) and BRAF mutations in serial plasma samples from 42 refractory mCRC patients to Folfox + cetuximab or dasatinib. 98% of the plasma were found mutant before or during treatment. 50% of KRAS mutant samples were missed by tumor tissue analysis before treatment. 4.8% of patients were found BRAF mutant by tumor tissue analysis while 7% were found mutant by ctDNA analysis. Longitudinal plasma analysis shows that 80% of initially WT patients acquire at least one RAS or BRAF mutation during treatment and that 38% of initially mutant patients acquire at least one newly KRAS or BRAF point mutation during treatment. CtDNA analysis allows tracking acquired resistance by studying the real-time clonal evolution of the tumor Patients may harbor mutations at very low frequency on ctDNA down to 0.01% before initiation or during treatment revealing the need of a high sensitive technique to detect mutant subclones. Altogether, our results indicate that plasma analysis could advantageously replace tumor tissue analysis and enables longitudinal examination of tumor molecular profiling.

Liane Deligdisch
Mount Sinai Medical Center, NY, USA
Title: Stage I Ovarian Carcinoma: the Challenge of Early Diagnosis and Management

Biography: Dr. Liane Deligdisch graduated Medical School in Bucharest, Romania. Following positions were: Gynecologist and General Physician in Romania until 1963, Pathologist at the Ichilov Hospital, Tel Aviv Medical School, Israel 1963 to 1975, Visiting Professor Magee Women Hospital in Pittsburgh, Pa.; 1975-6 Boston Free Hospital for Women, Harvard Medical School ; 1976 to present The Mount Sinai School of Medicine, full Professor of Pathology and Obstetrics-Gynecology and Attending since 1986. Founded the division of Gynecologic Pathology and directed the course of Gynecologic Pathology at the Medical School, Authored 143 peer reviewed articles, 7 textbooks on Gynecologic Pathology.

Abstract: Ovarian carcinoma is a highly lethal gynecological neoplasm, mostly diagnosed late due to asymptomatic early stages and lack of reliable tumor markers. In recent years, progress in systematic early detection and precursor stage identification of other malignant tumors was associated with a more favorable outcome, while for ovarian carcinomas morbidity and mortality statistics have not changed much over the past 5 decades. Compared to all stage ovarian carcinomas cases, where survival rates reach a mere 32%, the stage I ovarian carcinomas cases (confined to the ovaries) have an 85% five year survival. Our clinical-pathologic studies revealed that serous ovarian carcinomas, the most numerous histological type overall, represent a minority (less than 1/3) of stage I ovarian carcinomas. Early diagnosed ovarian carcinomas occur mostly in younger patients with associated symptomatic pathology related to hyperestrogenic states: endometriosis, endometrial hyperplasia and neoplasia, infertility. Histologically, these cases are of endometrioid, mucinous and clear cell types. Early diagnosed ovarian carcinomas of serous type are often asymptomatic, affect older patients, some BRCA positive, with personal and family histories of breast cancer; these patients undergo frequent medical examinations that may be the reason for early interception of aggressive ovarian carcinomas. Prophylactic salpingo-oophorectomy specimens revealed in morphometric (computerized image analysis), immunohistologic and molecular testing, significant preinvasive histological changes in ovaries and fallopian tubes fimbriae. Stage I ovarian carcinomas are a heterogeneous group of tumors with a different histological distribution, requiring different therapeutic approaches as compared to all stages ovarian carcinomas. Chemotherapy is not indicated in some cases and chemotherapeutic agents should be different than those used for advanced ovarian carcinomas. Despite their histological heterogeneity, stage I ovarian carcinomas may have a genetic similarity. It was demonstrated that in other tumors, the presence of cancer stem cells was associated with a more aggressive biologic behaviour and acquired resistance to chemotherapy. Preliminary studies of stage I ovarian carcinomas suggest the presence of the cancer stem cells in some of the serous histologic type. These findings are shedding light on early ovarian carcinogenesis and may have implications in the choice of therapeutic approach.

Rodrigo de Almeida Toledo
Spanish National Cancer Centre (CNIO), Madrid, Spain
Title: Clinical validation of prospective liquid biopsy monitoring in patients with wild-type RAS metastatic colorectal cancer treated with FOLFIRI-cetuximab

Biography: Rodrigo A. Toledo, MSc, PhD, graduated in Biosciences and Biomedical Sciences at the University of São Paulo, Brazil, where he later received his Masters and Doctorate degrees in 2007 and 2010, respectively. He completed his postdoctoral work at The University of Texas Health Science Center at San Antonio, USA, in Dr Patricia Dahia's laboratory, before joining the Clinical Research Program at the Spanish National Cancer Research Centre (CNIO) in Madrid, Spain. Dr Toledo was directly involved in the establishment of the genetic screening programme for multiple endocrine neoplasias at the largest public hospital in South America, Hospital das Clínicas, São Paulo, Brazil. Dr Toledo has identified and characterized functionally pathogenic mutations in new susceptibility genes of hereditary endocrine neoplasias using whole-exome sequencing.

Abstract: Cancer genomics and translational medicine rely on the molecular profiling of patient's tumor obtained during surgery or biopsy. Alternatively, blood is a less invasive source of tumor DNA shed, amongst other ways, as cell-free DNA (cfDNA). Highly-sensitive assays capable to detect cancer genetic events from patient's blood plasma became popularly known as liquid biopsy (LqB). Importantly, retrospective studies including small number of selected patients with metastatic colorectal cancer (mCRC) patients treated with anti-EGFR therapy have shown LqB capable to detect the acquired clonal mutations in RAS genes leading to therapy resistance. However, the usefulness of LqB in the real-life clinical monitoring of these patients still lack additional validation on controlled studies. In this context, we designed a prospective LqB clinical trial to monitor newly diagnosed KRAS wild-type (wt) mCRC patients who received a standard FOLFIRI-cetuximab regimen. We used BEAMing technique for evaluate cfDNA mutations in KRAS, NRAS, BRAF, and PIK3CA in twenty-five patients during a 2-y period. A total of 2,178 cfDNA mutation analyses were performed and we observed that: a) continued wt circulating status was correlated with a prolonged response; b) smoldering increases in mutant cfDNA were correlated with acquired resistance; while c) mutation upsurge/explosion anticipated a remarkable clinical deterioration. The current study provides evidences, obtained for the first time in an unbiased and prospective manner, that reinforces the utility of LqB for monitoring mCRC patients.

Rosario M. Sanchez-Martin
University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (GENYO), Spain
Title: Cancer Therapy and Diagnosis using engineered nanoparticles

Biography: Rosario M. Sánchez Martín has developed her research career between the UK and Spain. For the past 14 years she has been working in the area of nanotechnology in biomedicine. She has developed a variety of nanotechnologies to allow the efficient delivery of a wide range of cargos into cells for a number of in vitro and in vivo applications. Nowadays, Dr. Rosario M. Sánchez-Martín leads the research team NanoChemBio of the University of Granada in Spain. She is a world leader in the field of nanoparticles and their biological applications and Lecturer in the School of Pharmacy at the University of Granada. She finished her PhD at the University of Granada in 2002. She spent 9 years in the UK, firstly as postdoctoral fellow at the University of Southampton and later, in 2006, as independent researcher at the University of Edinburgh when she was awarded a prestigious Dorothy Hodgkin Fellowship from the Royal Society. In January 2011, she was awarded a Marie Curie CIG reintegration fellowship and she moved to the University of Granada. Since then, she has worked on transferring all her expertise and know-how in designing and developing nanotechnology-based platforms to the University of Granada. In 2013, Dr. Sánchez- Martín has been granted with her own research lab in the Centre for Genomics and Oncological Research (GENYO) integrated by Pfizer - Universidad de Granada - Junta de Andalucía. Nowadays, her research activity is focused on the development of nanotechnology based platform for diagnosis and personalized medicine (sl.ugr.es/UGRNanoChemBio). She is founder and chief of the Scientific Advisory board of the start-up biotech company Nanogetic S.L (http://www.nanogetic.com/).

Abstract: Despite rapid advances in the molecular profiling of cancer and its targeted therapy, the lack of sensitive and affordable assays for early diagnosis of aggressive primary cancer and recurrence is the most important obstacle to curbing mortality by cancer. Our lab is focussed in the design of nanodevices for cancer diagnosis and therapy. Our research team has designed several strategies to conjugate efficiently therapeutics and diagnostic cargoes to engineered nanoparticles (NPs). Relevant cargoes such as proteins, oligonucleotides, both DNA and RNA, peptides, drugs, sensors and fluorophores have been conjugated to them and successfully delivery inside cells. Furthermore, by gene expression and proteomic profiling studies, was shown that nanospheres did not induce significant alteration of nanofected cells. Recently we have developed a method to determine the doses of NPs in a reproducible and reliable manner. Herein our more recent developments in the design of multifunctional nanoplatforms for cancer therapy and diagnosis will be presented.

Clinical Cancer Research

Session Introduction

Yanling Ma
University of Southern California, USA
Title: "HER2 Status in Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Adenocarcinoma for Entry to the TRIO-013/LOGiC Trial of Lapatinib "


Abstract: HER2/ERBB2 status is used to select patients for HER2-targeted therapy. HER2/ERBB2 amplification/overexpression of upper gastrointestinal (UGI) adenocarcinomas was determined locally or in two central laboratories to select patients for the TRIO-013/ LOGiC trial of chemotherapy with or without lapatinib. Patients selected locally had central laboratory confirmation of HER2 amplification for inclusion in the primary efficacy population. HER2 was assessed with PathVysion or IQ PharmDx FISH and HercepTest immunohistochemistry assays. Associations with outcomes were retrospectively evaluated. Overall, HER2 status was determined in UGI cancers from 4,674 patients in a central laboratory for eligibility (1,995 cases) and for confirmation of local HER2 results (333 cases). Of 1,995 adenocarcinomas screened centrally, 322 (16.1%) had HER2-amplified disease with 29 (1.5%) showing HER2 genomic heterogeneity. Men and older patients had higher rates of amplification. Of 545 patients accrued to the trial (gastric, 87.3%; GEJ, 8.3% and esophageal cancer, 4.4%), 487 patients (89%) were centrally confirmed as having HER2-amplified disease.Concordance between central and local HER2 testing was 83%. Concordance between PathVysion and IQ PharmDx FISH assays was 99% and FISH in the two central laboratories was 95%. Lapatinib-treated Asian participants and those less than 60 years had significant improvement in progression- free survival (PFS), particularly among those whose cancers had 5.01–10.0 and >10.0-fold amplification of HER2. In conclusion, HER2 is commonly amplified in UGI adenocarcinomas with amplification highly correlated to overexpression, and HER2 amplification levels correlated with PFS. While HER2 genomic heterogeneity occurs, its prevalence is low.

Hospital General of Granollers, Barcelona, Spain
Hospital General of Barcelona
Title: Placental immune editing switch (PIES): immunomodulatory pathways active in both breast cancer and placental tissues from a unique clinical and genomic case report

Biography: Miguel H. Bronchud was born in Barcelona but went to school in Italy (Liceo Massimo d'Azeglio, Turin) and to university in England: BA, MA in Natural Sciences (Biochemistry Part II) at the University of Cambridge and BM BCh at the University of Oxford. Following his MRCP (London 1986) he obtained a DM at Oxford and PhD Madrid. He has been a pioneer on Rhu-G-CSF (Filgrastim) and stem cells (CD34+) as well as cancer cells immune escape mechanisms related to mammalian placental feto-maternal gene expression programs

Abstract: The basic theoretical question asked was : why should cancer cells invent ‘de novo’ new and unique immune escape mechanisms (during each single and different human carcinogenesis process) if they might “simply” use (or partially ectopically express) intrinsic immune escape gene programs naturally developed during mammalian evolution over millions of years to allow for materno-fetal immune tolerance? Genomic analysis (Nanostring Inc, Seattle, WA, USA) was carried out in primary breast cancer with metastatic homolateral axillary lymph nodes as well as placenta tissue (both uterine decidual tissue and term placenta tissue) from a pregnant woman (same patient). Gene expression profiling of paired non-self and self tissues (i.e. placenta/uterus; breast cancer/normal breast tissue; metastatic lymphnode/normal lymphnode tissue) was performed using the PanCancer Immune gene panel, a 770 Nanostring gene expression panel. Our findings reveal overlapping in specific immune gene expression in placenta and cancer tissue, suggesting that these genes might play an important role in maintaining immune tolerance both physiologically (in the placenta) and pathologically (in the cancer setting). Placenta and uterus, breast tissues (tumor and normal) and lymph node tissues (tumor and normal) formed their own RNA transciption cluster, suggesting that tissue specific gene expression patterns were well preserved during experimental procedures and that tissue specific expression pattern overshadows gene expression differences within each tissue type. We then analyzed differential expression within each tissue type (i.e. matching for the analysis placenta with uterus, breast cancer with normal breast tissue and node positive with node negative tissue). Among the 583 genes analyzed, 103 genes were upregulated > 1.5 fold in placenta versus uterus, while 258 genes were downregulated at least 1.5 fold. Using the same cut-off, 258 genes were upregulated and 44 genes downregulated in breast tumor versus normal breast tissue, and 178 genes were upregulated while 146 genes downregulated in tumor bearing lymph node versus non-involved lymph node.

Eleazar Lara Padilla
Medicine School, Instituto Politécnico Nacional, Mexico
Title: Metastasis Risk Reduction Related with Beta-Blocker Treatment in Mexican Women with Breast Cancer

Biography: Bachelor’s degree in Medicine, Master’s degree and Ph.D. in High Performance Sports. At present, I am working like a Researcher in Clinical and Biomedical Studies and as a Professor in the School of Medicine at National Polytechnic Institute, Mexico City My lines of research are oxidative stress in performance sports, chronic degenerative diseases and cancer. I got around 10 national and international Awards related to Science. I had around 50 published articles in international journals and one national patent related to a new neuronal biomarker for breast cancer

Abstract: Background: Breast Cancer (BCa) is the most common malignant tumour in Mexican women. In BCa, several studies have linked β2-adrenergic receptor activation with increased tumour growth and progression as related with Epinephrine-NorEpinephrine (E-NE) stimulation. The aim of this study was to describe Beta-Blocker (BB) treatment related with reduction of the risk of metastasis in Mexican patients with BCa. Materials and Methods: We collected data of 120 patients seen at the HOSGENAES, all of these with a histopathological diagnosis of BCa. Four groups of patients were divided as follows: without Systemic Arterial Hypertension (SAH); with SAH treatment with non-selective BB; with SAH treatment with selective BB, and with SAH treatment with other antihypertensive drugs. Chi-square, Mantel-Haenszel, Student t, and ANOVA tests were performed for data analysis. Results: On average, patients were 54.8±11.8 years of age. Risk factors such as smoking and consuming alcohol exhibited a frequency of 33 and 36.5% respectively. Clinical stages III- IV were found in 50% of patients, while, 30% of patients had arterial hypertension (n=29 and N=96, respectively) and 17.5% used BB. One hundred percent of patients with arterial hypertension treated with BB for β1 - and β2 -adrenergic-receptors did not present metastasis globally, but patients treated with β1 BB presented 30% of metastasis while patients treated with no BB or without SAH had around 70% of metastasis. Conclusions: In Mexican patients with BCa and SAH treated with non-selective (β1-and β2-adrenergic receptors) BB, a decrease in the risk for metastasis was observed at the time of diagnosis.

Cindy Bandala
Instituto Nacional de Rehabilitación, Mexico
Title: Beta-blockers Effect on inhibition of bone resorption in patients with Breast Cancer

Biography: Bachelor’s degree in Medicine, Master’s degree in Biochemistry and Microbial Genetics, Master’s degree in Health Science, Ph.D. in Medical Research (Experimental Oncology). At present, im working like a Researcher in Clinical and Biomedical Studies in the National Rehabilitation Institute, Mexico City and as Associate Professor (Research Methodology and Biostatistics) Naval Medicine School, Secretary of the Navy (Mexico City). My lines of research are neurogenesis and neurochemistry of cancer. I got around 10 national and international Awards related to Science. I had around 30 published articles in international journals and one national patent related to a new neuronal biomarker for breast cancer.

Abstract: Breast cancer (BCa) is the leading cause of cancer death in women, one of the biggest public health problems worldwide. Tumorogenesis have been related to Epinephrine-NorEpinephrine (E-NE) and β1- and β2-adrenergic receptors. E-NE has been related to different process involved in a wide kind of tumors and could stimulate osteoclast activity through adrenergic receptors. BCa patients decrease their bone mineral density (BMd). Low doses of propranolol suppress bone resorption by inhibiting RANKL-mediated osteoclastogenesis in rats. Our aim was to describe Beta-Blocker (BB1&2) treatment decreases BMd resorption in patients with BCa. Materials and Methods: We collected data of 243 patients (191 BCa, 52 no BCa) treated in the ABC hospital with BB1&2 (doses 1.25 a 5 mg/day) and patients without BB1&2. BMd one density was evaluated by densitometry, at the level of the vertebral bodies of lumbar spine and hip bilaterally, expressed in Standard Deviation (SD). A p value <0.05 was taken as statistical significance. Results: The mean of age was similar between BCa non BCa patients (57.12±0.66 years). BCa patients treated with BB1&2 had higher BMd than patient not treated with BB1&2, in age of risk for menopause (0.40±0.97 vs. -1.31±1.02 SD, p=0.0001) and in younger patients (1.28±0.38 vs. -0.66±0.92 SD, p=0.0001); these results were similar in no BCa patients. BCa patients with clinical stage III-IV, HER2 negative and with metastases showed less BMd (p<0.05 respectively). Conclusions: BCa Patients treated with BB1&2, were protected 24 times to the risk of osteoporosis/osteopenia, and higher BMd resorption are related to malignancy criteria

Zeng Xi
The West China Second University Hospital, China
Title: HPV Infection versus Vaginal Intraepithelial Neoplasia and Cervical Stump Cancer in Women Received Subtotal Hysterectomy

Biography: Dr. Zeng Xi has completed his Doctor’s degree from West China Medical College, Sichuan University, China. He is currently work as a resident doctor in the major of gynecology oncology in the West China Second University Hospital, Sichuan University. He has also published several articles on SCI journals and gave several oral presentations on international academic congresses.

Abstract: Objective: To retrospectively report series cases of patients received subtotal hysterectomy, evaluate their relationship with human papillomavirus (HPV) infections and vaginal intraepithelial neoplasia (VAIN) or cervical stump cancer. Methods: We retrospected and analyzed the data of patients with cervical cancer or cervical stump cancer in the West China Second University Hospital, Sichuan University (the largest women hospital in the western of China) from 2005 to 2015. Results: There were 9481 patients received subtotal hysterectomy in our hospital and 3218 losing following-up. Among the rest 6263, there were 1071 got HPV infections (mean HC II value of 124.3), HPV-16, HPV-18, HPV-58 were the most common types. And 311 with grade I of vaginal intraepithelial neoplasia (VAIN), 108 with VAIN II, 89 with VAIN III and 61 occurred with cervical stump cancer. Fifty-six among the 61 suffered cervical stump HPV infections after the subtotal hysterectomy with a mean HC II value of 483.18. The interval time between subtotal hysterectomy and stump cancer was 8.89 years. Women with HPV positive versus negative results had non-benign cytology 77.2% versus 28.3% (p<0.001). Conclusion: Among the patients who received subtotal hysterectomy, there are strong relationships between HPV infection and VAIN or cervical stump cancer. With gynecologic surgeons more experienced and operation technology progressed, it is significant to weigh the necessity to operate subtotal hysterectomy against the risk of cervical stump cancer. If the operation cannot be avoided, further HPV and cervical stump cancer screening is mandatory.

Tumor Virology and Pathology

Session Introduction

Hossein Ashrafi
Kingston University, UK
Title: The role of Human Papillomaviruses infection in the development of Breast cancer

Biography: Dr. Hossein Ashrafi obtained hisPhD in Cancer Biology from Beatson Institute for Cancer Research, Glasgow University in 1998. In the same year he was offered a fellowship in the Medical Oncology, He was awarded a Royal Society Developing World Study Visit fellowship for distinguished research work. Dr. Ashrafi joined Kingston University London in 2009 where he is an Associate Professor, course leader for cancer biology and teach on a range of modules, supervise PhD students, act as editorial board member of journals, and lead an active research group on the role of HPV and cancers and therapeutic approaches toward HPV related cancer.

Abstract: Despite the high incidence of breast cancer, cause of breast cancer remains unexplained by the known epidemiology. There are many probable and well established risk factors including genetics factors and environmental and life style factors such as tobacco, alcohol, radiation, hormones and obesity. However, 60-70% of breast cancers cases have no known risk factor. Infectious agents are also implicated in cancer carcinogenesis. Human papillomavirus (HPV) have been examined as probable aetiological agents of breast cancer since 1992. However, HPV’s involvement is still highly controversial. Building upon previous research findings, this study aims to detect and examine the presence and biological activity of 12 HR HPV types, in both cancerous breast tissue, as well as benign breast tissue specimens. DNA/RNA/Protein purification was carried out on 110 abnormal fresh breast tissue specimens from Kingston Hospital-UK. The presence of 12 HR HPV types was examined and determined using PCR. Additionally, PCR products were sequenced to confirm the results. To inspect the biological activity of HPV, expression of HPV proteins was investigated using western blot and dot blot. Data obtained from this study demonstrate 45% of breast cancer patients’ samples were positive for the presence of HR HPV types. The expression of HPV proteins in these samples was detected in few breast cancer cases which confirms the virus is biologically active and may have a role in the development of breast cancer. These results are reinforcing the need for further research to establish a causal link between HPV and breast carcinogenesis.

Cancer Cell and Model Systems

Session Introduction

Augusto Pereira Sanchez
Gregorio Marañón University General Hospital, Madrid, Spain


Abstract: Introduction: In 1931, Simpson et al. coined the term “peritoneal carcinomatosis” to describe the regional spread of ovarian tumors as localized or extended with involvement of the peritoneal serous membrane and neighboring anatomical structures. Research into the origin of peritoneal carcinomatosis is based on two phases in a woman’s life: - Embryo development: During week 3, the bilaminar disc becomes a trilaminar disc called the mesoderm. Inside the lateral plate mesoderm, the coelomic cavity is divided into 2 layers: the parietal (somatic) mesoderm, which gives rise to the parietal peritoneum and pleural surfaces; and the visceral (splanchnic) mesoderm, which gives rise to the visceral peritoneum, visceral surface of the pleura, gonadal stroma, and the muscular layer of the hollow viscera and its mesenteries. - Tumor spread: Transcoelomic metastasis and hematogenous and lymphatic spread were reviewed in 2006 by Tan, who found that metaplasia of pluripotent stem cells in the peritoneum was involved in the pathogenesis of ovarian cancer. This involvement takes the form of a synchronous malignant transformation at multiple foci and may cause intraperitoneal field cancerization. Pluripotent stem cells play a role both in the development of the embryonic peritoneum and in the spread of transcoelomic tumors. Consequently, knowledge of the origin of these cells (embryonic or current) could be extremely useful. The many markers that act during the embryonic period can affect descendants, that is, cells are already marked before specification and differentiation are activated. Thus, programmed activation could be attributed to genetic and epigenetic changes.

Cancer Biomarkers

Session Introduction

Chiang Mai University, Thailand
Title: p16 as a Possible Surrogate Marker for High-risk Human Papillomaviruses in Oral Cancer

Biography: Professor Dr. Anak Iamaroon was graduated from Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand in 1987, received Master’s Degree in Oral Pathology from the School of Dentistry, University of Minnesota, USA in 1992 and Ph.D. in Oral Biology from Faculty of Dentistry, the University of British Columbia, Canada in 1996. He is currently a full professor in Oral Pathology at Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand. He has published more than 50 scientific papers and text chapters. His research interest is mainly in the pathogenesis, biomarkers, and risk factors of oral cancer. Recently, he and his co-workers have investigated a role of HPV for the tumorgenesis of oral squamous cell carcinoma and the use of p16 as a surrogate marker for HPV infection.

Abstract: Background: High-risk human papillomaviruses (HR-HPV), particularly types 16 and 18, have been found to play an important role in head and neck cancer, including oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC). p16, a cell cycle inhibitor, has been postulated as a surrogate marker for HR-HPV, since p16 is aberrantly overexpressed, especially in HR-HPV-positive OPSCC. However, p16 as a surrogate marker for HR-HPV infection in cancers of the oral cavity remains controversial. Objective: The objectives of the study were to investigate the expression of p16 and the presence of HR-HPV in OSCC and oral verrucous carcinoma (VC) and to determine if p16 could be used as a surrogate marker for HR-HPV in OSCC and VC. Materials and methods: Forty one formalin-fixed, paraffin-embedded tissues of OSCC (n = 37), VC (n=4) with the clinical and histopathologic data of each case were collected. The expression of p16 was determined by means of an immunohistochemical technique. The staining intensity and numbers of the stained cells were scored and analyzed. The presence of HPV types 16 and 18 was detected by polymerase chain reaction (PCR). Descriptive statistics were employed to describe the demographic, clinical, and histopathologic parameters. The association between p16 overexpression, HR-HPV and all variables was determined by Fisher's exact test, odds ratios (ORs) and their corresponding 95% confidence intervals (CIs).In addition, the use of p16 as a surrogate marker for HR-HPV was analyzed by the sensitivity and specificity tests. Results: p16 was overexpressed in 8/37 cases (21.6%) of OSCC and 2/4 cases (50%) of VC.HPV-16 was detected in 4/34 OSCC cases (11.8%) and HPV-18 was detected in 1/34 OSCC cases (2.9%).A co-infection of HPV-16/18 was detected in 1/4 VC cases (25%).Both p16 overexpression and HR-HPV were significantly associated with young patients with bot OSCC and VC (p < 0.05, OR 20, 95% CI 1.9-211.8; p < 0.05, OR 23.3, 95% CI 2.4-229.7, respectively).p16 was able to predict the presence of HPV-16/18 in OSCC with 40% sensitivity and 79.3% specificity and in VC with 100% sensitivity and 66.7% specificity, respectively. Conclusions: p16 overexpression was found in 24.4% of both OSCC and VC. HR-HPV, regardless of types, was detected in 15.8% in cases of OSCC and VC combined. The results of sensitivity and specificity tests suggest that p16 can be used as a surrogate marker for HR-HPV in OSCC and VC.

University HassanII of Casablanca, Morocco
Title: Identification of Three bio-markers associated to gynecologic and breast cancer using real time PCR in Morocco’


Abstract: Gynecologic and Breast cancers (cervical cancer, ovarian cancer ...) represent a real public health problem in Morocco. In 2011 these cancers accounted for 60% of all cancers among women and 50% of cancer among women treated at the National Institute of Oncology. Currently, more research is directed towards the molecular signatures of different cancers including research on newly discovered biomarkers and highlighted called miRNAs that allow early diagnosis of these cancers. Among these, the identification of MicroRNAs (miRNAs), which are epigenetic biomarker able to regulate promoters of genes of cancer cells and which are released early in the general circulation, thus providing potential targets for diagnosis. The aim of this study is to detect this biomarkers in fresh biopsies and to determinate the expression profile of microRNAs. It is in this context that our research project proposes identify some MiRNAs specific to each type of gynecologic and breast cancers among the Moroccan population and that have been demonstrated as early biomarkers of these cancers in previous studies. These MiRNAs were extracted and purified with specific methods from fresh biopsies collected from Obstetrics gynecology service of CHU Ibn Rochd of Casablanca, and amplified using real time PCR. These newly discovered molecular signature of cancer can contribute to an early and selective cancer diagnosis if the molecular profile is well established and can provide a new way of prevention to ensure a better prognosis and improving therapeutic monitoring for patients in Morocco for breast and gynecological cancer or another type of cancers (vulva, endometrial…).

Cancer Detection and Imaging

Session Introduction

Mojgan Ahmadzadeh Raji
University of Tehran, Iran
Title: Design and Synthesis an Aptameric Nanosystem Based Gold Nanoparticles For Separation and Detection of HCT116 (Related to Colon Cancer)

Biography: Dr.Mojgan Ahmadzadeh Raji has completed her Ph.D in Nano-biotechnology from University of Tehran as a common project with York University, Toronto, Canada. She began her career as a researcher in National Institute of Genetic Engineering and Biotechnology (NIGEB) and she continued her research work in Dr.Rastegar Central laboratory in University of Tehran from 2001 to present. Her main investigation is divided into 2 sections the first one is design and implementation of Nanobiosensors for cancer detection and second one is design Aptamer Drug Conjugate for apoptosis induction. She has published more than 22 papers and conference papers and she has cooperation with IEEE conference.

Abstract: Early detection of circulating tumor metastasis cells calls for the design and implementation of emerging nano-bio-systems in order prevent the development of disease to other tissues. Among various bio-recognition elements, aptamers offer great advantages of cost-effective and efficient to develop such nano-bio-systems for cancer detection. Herein, in this study we synthesis an aptamer immobilized on the surface of gold electrodes and gold nano-particles immobilized on surface ITO. For this purpose, we investigated a label-free aptasensor for detecting of colon cancer cell using HCT116 as target cell and HE-p2 as control cells. An aptamer specific to carcinoembryonic antigen (CEA) presenting on the surface of colon cancer cells was employed to capture the colon cancer cell. Since both ends of the aptamers have the ability to connect to surface electrode, but an amine Hexamethylene as a linker attached to 3'-end of aptamer to interface for connecting covalently bound to a gold electrode and the gold nanoparticles was added to the aptamer sequence. To evaluate the performance nano system (aptamer + linker + gold or gold nanoparticles deposited on the surface of ITO electrode), the 5 ' end of aptamer labeled with FITC, used for evaluate HCT116 colon cancer cell line attachment. Gold nanoparticles synthesized by reduction tetrachloroaurate ion with sodium citrate as a classic method in the literature. The results of the test, such as fluorescence, flow cytometry, cells HCT116 connection to the aptamer approved the 60.19 percent attachment of aptamer to target cell. The average size of nanoparticles with Dynamic light scattering (DLS) method and zeta potential was about 31 nm and -42.29 mV respectively. Capture aptamers have been covalently immobilized on the surface of gold electrode in the first approach and on the surface gold nanoparticles (GNPs) in the second approach through self-assembly monolayer of 11-mercaptoundecanoic acid (11-MUA) activated with (EDC/NHS). The cyclic voltammetry (CV) and chronopotentiometry (CP) methods were also used to electrodeposit GNPs on the surface of indium tin oxide (ITO). In this work, the CV method is also used to demonstrate the conjugation of substrates and aptamers and identify the cancer cell capturing events. These measurement results shows (LOD=7) and (LOD=6) for Gold electrode and Gold nanoparticles immobilized on ITO respectively with high sensitivity and selectivity. Additionally, Field Emission Scanning Electron Microscopy (FE-SEM) confirmed the deposition of GNPs on ITO and the attachment of target cells on the aptasensor. The output of ITO electrode to control cells is constant and equal to 8 nanoamper and potentiostat output for cancer cells increased with number of cells from 26.38 μA and 63.71 μA for 6 and 50 cells per ml respectively. For Gold electrode the output for control and cancer cells was 0.2 and 0.5 μA for 6 and 50 cell/mL respectively. According to statistical analysis there is no significant difference between the results obtained in the three replications of each step coverage which indicates repeatability tests. The results show design and using of aptameric nanosystem attached Gold in nano biosensor based transparent ITO with lower LOD is applicable.

Carcinogenesis & Mutagenesis

Session Introduction

Hari K. Bhat
University of Missouri-Kansas City, Kansas City, MO
Title: Resveratrol and resveratrol analogs: Antioxidant and anticancer activity

Biography: Dr. Bhat received his B.Sc. in Biology and Chemistry, and M.Sc. in Organic Chemistry from University of Kashmir, Kashmir, India. He received his Ph.D. in Biochemistry from the University of Texas Medical Branch, Galveston, Texas.

Abstract: Most of the currently available drugs to treat breast cancer (BC) have major limitations in long-term use because of significant toxicities or adverse effects associated with these drugs. Published studies have established that resveratrol (Res), possesses antioxidant, anti-inflammatory and anticancer activities. Unfortunately, however, the available evidence supports the conclusion that its potency in preventing or treating BC is relatively modest at best. We hypothesize that this problem can be successfully addressed through synthesis of Res analogs with appropriate structural modifications. Thus, we have synthesized a series of novel compounds that resemble the basic Res skeleton but contain some structural modifications with different pharmacophoric groups. We evaluated these compounds for their cytotoxicities against several BC cell lines. We demonstrate that one of the synthesized compounds 4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol} (TIMBD) has significantly higher potency than Res in inhibiting the growth of all BC cell lines that we tested. Moreover, TIMBD did not have any detectable detrimental effect on the growth of normal (non-neoplastic) human breast cells and other cell types of the brain. Additionally, increased oxidative stress has been suggested to contribute to development of breast tumors and many other diseases. Our preliminary results suggest that TIMBD also functions to decrease levels of oxidative stress, induce mRNA and protein expression levels of antioxidant defense genes such as NQO1, SOD3 and Nrf2 in normal (non-neoplastic) breast cell lines as well as in human SVGA astrocytes but not in BC cells. Our results thus suggest that TIMBD is not only cytotoxic towards BC cells but can also help to protect normal cells against increased oxidative burden. Thus, chemotherapeutic agents that have the potential of specifically killing, or inhibiting the growth of, BC cells with relatively minimal toxicity towards normal cells, would be expected to have a significant therapeutic advantage in selectively targeting BCs.

Alaa M. Shuibat
Gazi University, Turkey
Title: Evaluation of Diagnostic and Prognostic Role of Cancer Stem Cells and Aldehyde Dehydrogenase Activity in Different Salivary Gland Tumors


Abstract: Salivary gland tumors exhibit a diverse range of histological appearance because of the various shapes and arrangements of the neoplastic cells which makes the diagnostic and prognostic predictions a real challenge. A subset of cells, tentatively called cancer stem cells (CSCs) have been associated with tumor initiation, drug resistance, and tumor aggressiveness. Recent evidence suggests that enhanced activity of aldehyde dehydrogenase 1 (ALDH 1), CD44, CD24, CD166, as hallmark of cancer stem cells. For that reason this study aims to determine the distribution of the cancer stem cell markers ALDH1, CD166, CD44 and CD24 among different benign, malignant salivary gland tumors as well as normal salivary gland tissues. 24 malignant salivary gland tumors (6 mucoepidermoid carcinoma, 6 polymorphous low grade adenocarcinoma, 8 adenoid cystic carcinoma, 2 carcinoma ex-pleomorphic adenoma, 2 acinic cell carcinoma) 24 benign salivary gland tumors (21 pleomorphic adenoma, 3 basal cell adenoma) and 7 normal salivary gland tissues from the archive of Gazi University Faculty of Dentistry were enrolled in the study. Demographic features and 7 years follow up data of patients were recorded. A total of 55 blocks have been immunohistochemically stained for CSCs markers ALDH1, CD44, CD24, and CD166. ALDH1 expression was down regulated in malignant tumors (P 0.034). Decreased ALDH expression was noted in high grade tumors. The lack of ALDH1 expression in adenoid cystic carcinomas (P 0.000) and basal call adenomas in relation to other tumors (P 0.026) were statistically significant. Malignant SG tumors displayed statistically significant up regulated CD166 expression (P 0.002). Loss of CD166 was determined both in metastasising/recurrent and high grade tumors in comparison to non-metastisizin/non-recurrent and low grade tumors. Diminishing CD44 expression was noted in benign and malignant tumors in descending order while metastisizing/recurrent tumor had higher CD44 expression in comparision to non-metastasizing / non-recurrent tumors. Benign SGT showed higher CD24 expression in comparison to malignant tumors. There was a higher CD24 expression in metastasising /recurrent tumors. Down regulation of ALDH expression by age also showed statistical significance (P 0.007). In conclusion there was a statistically significant up regulation of CD166 and down regulation of ALDH1 expression in malignant salivary gland tumors. This data suggested that these molecules could be useful markers for cancer stem cells in salivary gland tumors. Our results also supported the literature information that variations in expressions of these markers might be correlated with the prognosis of salivary gland tumors. The lack of ALDH1 expression in adenoid cystic carcinoma (Ad CC) suggested the potential role of this molecule as a diagnostic marker in differential diagnosis of Ad CC.

Cancer Management & Prevention

Session Introduction

Yekaterina Koshkareva
MD Anderson at Cooper University, Department of Otolaryngology–Head and Neck Surgery, USA
Title: Stereotactic Body Radiotherapy Treatment for Recurrent, Previously Irradiated Head and Neck Cancer

Biography: Yekaterina Koshkareva, MS, FACS is a head and neck cancer specialist practicing at Cooper University Hospital, Department of Surgery, Division of Otolaryngology at Camden, NJ, United States. Dr. Koshkareva has received her doctorate degree at Temple University, Philadelphia PA, where she stayed to complete her residency training in Otolaryngology, Head and Neck Surgery. She received her fellowship training in advanced head and neck surgical oncology at the University of Pittsburgh Medical Center, Pittsburgh, PA. Dr. Koshkareva has been a part of MD Anderson at Cooper University hospital since 2013 taking care of patients with a variety of head and neck oncologic processes.

Abstract: Locally recurrent, previously irradiated primary head and neck tumors have historically been associated with poor outcomes. Stereotactic body radiation therapy (SBRT) has emerged as a feasible and promising treatment option for tumor recurrence, particularly in non-surgical candidates. We performed a prospective analysis of 25 patients treated with CyberKnife for unresectable, recurrent head and neck cancer in a previously irradiated field. Median overall survival of the study population was 7.5 months; 8.3 months for non-metastatic patients. Low severe treatment-related acute (4%) and late (6%) toxicity rates were observed. No grade 4/5 toxicities were observed. Stereotactic body radiotherapy is a viable treatment option for patients with unresectable, recurrent head and neck cancer. Positive tumor control rates are achievable with minimal severe-toxicity. Although perhaps associated with patient selection, SBRT outcomes appear inferior to other treatment modalities.

Monica Denti
Institute of Hospitalization and Scientific Care (IRCCS), Italy
Title: Prospective observational and controlled study on rehabilitation intervention for cancer patients in department with dedicated team

Biography: Monica Denti is a young physiotherapist working in Arcispedale Santa Maria Nuova, IRCCS of Reggio Emilia, Italy, as a researcher. She has approached the cancer rehabilitation since she was a student with her thesis and this interest is continuing now: she works in cancer care hospital and she is also a professor in Modena and Reggio Emilia University, teaching cancer rehabilitation in the Physiotherapy Degree Course. She recently won a grant to carry out a project to improve rehabilitation for haematologic cancer survivors.

Abstract: People with cancer have to live for a long time with symptoms related to the disease and side effects due to the treatments. Cancer rehabilitation is an important part of the multidimensional patient care: its global and early approach can help patients improve their quality of life (QoL), reducing disabilities caused by cancer or oncological treatments. The purpose of this study is to evaluate the effects of inpatient rehabilitation on QoL, function and rehabilitative needs in patients with cancer. Furthermore, it aims to investigate patients’ and care-givers’ perception about the quality of physical therapy intervention in hospital wards and to obtain information about symptoms, clinical characteristics and features related to bed rest and complications during hospital stay. The intervention group (IG) was composed by patients admitted in an oncologic ward with specifically trained health professionals: physiatrists and physiotherapists were trained to face the principal issues due to cancer care, and worked as a part of the multi-professional team of the oncologic ward. The control group (CG) included patients admitted in general wards, treated by non-dedicated rehabilitative team. Data were collected from wards’ registers, clinical records and evaluation scales. Specific questionnaires focused on clinical characteristics of patients admitted to hospital and their main concerns about rehabilitation needs. Both in IG and CG the rehabilitation program was offered as soon as patients clinical conditions were appropriate. IG patients showed better results in QoL, pain relief, adherence to rehabilitative program, and perception of physical therapy intervention as linked to the main needs of patients and their caregivers. In both group, an increase of the independence in ADL and a reduction of anxiety and depression were registered. Results suggest that inpatient rehabilitation for cancer survivors with a dedicated team can be more effective than rehabilitative intervention in general wards.

Monia Allisen Accogli
Institute of Hospitalization and Scientific Care (IRCCS), Italy
Title: Physical activity as a treatment for healthy quality of life: definition of therapeutic patient education intervention for haematologic cancer survivors

Biography: Monia Allisen Accogli is a young physiotherapist working in Arcispedale Santa Maria Nuova, IRCCS of Reggio Emilia, Italy, as a researcher. She has approached the cancer rehabilitation since she was a student with her thesis and this interest is continuing now: she works in cancer care hospital and she is also a professor in Modena and Reggio Emilia University, teaching cancer rehabilitation in the Physiotherapy Degree Course. She recently won a grant to carry out a project to improve rehabilitation for haematologic cancer survivors

Abstract: Cancer incidence is increasing, but prevention and therapy are improving, and an increase of survival is expected for the next decades. Several studies reported that cancer survivors have to cope with symptoms related to the disease and to treatment side effects. Some of the most important disabling symptoms for cancer patients are pain, cancer-related fatigue, movement disorders and psychological distress. An adequate program of physical activity (PA) can help patients at every stage of disease and information about this is required because clinicians often focus on cancer follow-up, surgical interventions, chemotherapy or other therapeutic strategies to cure cancer disease, but patients need counselling on PA program to manage fatigue and independence in activities of daily life. The aim of our project is to offer haematologic cancer patients a tailored program of PA and to support self-management after discharge, enabling people to use PA as a “not chemical drug”. This is the first Italian pilot study on haematological cancer patients and PA program for healthy life. Patients with haematologic malignancies will be assessed by 2 physiotherapists for the following issues: pain, fatigue, anxiety and depression, independence in ADL. A plan for a PA program will be set-up, with collaborative goal-setting approach, centred on patient needs and performances. Individual and group therapeutic education sessions will be offered to support patients managing their own condition and preventing complications due to the disease or anti-cancer therapies. Patients will receive information booklets concerning the principal topics about cancer, his consequences and treatments (symptoms and side effects management, aids and orthosis and how to live healthy after cancer diagnosis). An Italian program of self-management and PA for haematologic cancer patients will be set-up, specific information booklets will be prepared for the program. We expect improvements in pain, fatigue, self-efficacy, independence in ADLs and quality of life.

Cancer Genetics

Session Introduction

Sigurdur Ingvarsson
University of Iceland at Keldur, Iceland
Title: Genomic, proteomic and clinicopathological events in carriers of the Icelandic BRCA2 999del5 founder mutation

Biography: Sigurdur finished his B.Sc. degree in biology from the University of Iceland in 1979 and defended his Ph.D. thesis at Karolinska Institutet in Stockholm in 1989, based on his work on the MYC oncogenes in George Klein‘s laboratory at the Department of Tumor Biology. Subsequently he pursued his postdoctoral training on the ERBA oncogene in Björn Vennström´s laboratory at the Department of Molecular Biology, same institute. Back to Iceland his research projects were focusing on genetics and molecular biology of human cancer, mainly breast-, colon- and stomach cancer. He obtained associate professorship at the University of Iceland in 1998 and full professor in 2001, at the same university. He serves as the director of the Institute for Experimental Pathology, University of Iceland at Keldur.

Abstract: In carriers of BRCA1 and BRCA2 mutations there is an elevated risk increase of breast cancer and some other cancer types. Most of the mutations involved are of relatively high penetrance. The gross genomic instability detected in BRCA1 and BRCA2 tumours fits well with their documented function in DNA repair. Founder mutations in breast-cancer genes such as BRCA1 or BRCA2 permit analysis of a large number of cases that have the same mutation. When founder mutations have been identified it is possible to examine the prevalence of mutations in different populations and mutation-specific effects on penetrance and disease phenotype. This information can be useful in understanding the role played by these genes in the incidence of breast cancer, in order to target genetic testing, provide individual risk assessment, and design better therapeutic strategies. In Iceland a rare founder mutation has been detected in BRCA1, and a frequent one in BRCA2. Due to relatively high frequency, the Icelandic BRCA2 999del5 founder mutation has received the most attention, and has been analysed by several approaches. An extensive analysis on somatic events and changes in expression of oncogenes, tumour-suppressor genes and other genes affecting the tumour phenotype have been analysed in breast tumours of BRCA2 999del5 carriers. The accumulation of somatic gene mutations and changes in gene expression pattern is probably due to growth selection during the malignant progression in the context of insufficient DNA repair, in the form of control of cell turnover, differential and metabolic stage, preliminary crisis phase and apoptosis. Population-based studies have been performed on a large number of available BRCA2 999del5 carriers, regarding penetrance, cancer risk, patient survival and treatment, phenotype, clinicopathology, genetic modifiers and influence from the environment.

Organ Specific Cancers

Session Introduction

Khalid AlSindi
Department of Pathology, Blood Bank and Laboratory Médicine, Bahrain
Title: Assessment of a New Biomarker (M2PK 2 in 1) test as a potential tool for screening and early detection of colorectal cancer


Abstract: Colorectal Cancer (CRC) is a major cause of morbidity and mortality throughout the world. It accounts for over 9% of all cancer incidence. It is the third common cancer worldwide and the fourth common cause of death. In general, CRC is a disease of middle aged and elderly population with the majority being diagnosed after the age of 50 years(4). There are many reports from Asia and Africa where the incidence of CRC in the young adults, was significantly higher compared to the Western literature. The incidence of CRC in Bahrain based on the cancer registry cases in Gulf Cooperation Council Countries(8)) of 1998-2007 was 40/100,000 in men, and 32/100,000 in woman. Compared to other Gulf countries, Bahrain had higher incidence rates for CRC. Currently, Fecal Occult blood test (FOBT) is used to screen for CRCs despite its low (15-35%) sensitivity. The aims of this study are firstly, to establish the prevalence of CRC precursors in the Kingdom of Bahrain; secondly, to recommend the age of early enrolment in National Screening Program for Colorectal Cancer and finally, to compare the sensitivity of a new fecal tumor marker [M2-pyruvate kinase (M2-PK 2 in 1)] test as a potential replacement for the currently used FOB test. A new stool based M2PK 2 in 1 ( Tumor Biomarker ) test is now commercially available with a claimed superior (97% sensitivity, 98% specificity) reproducibility for detecting colorectal neoplasia at early stages, but to our knowledge no current regional data are available about its usefulness as a new test to substitute the FOB as a screening modality. One sample from each participating individuals is needed ( No dietary or medication control ). All collected samples shall be transferred to KHUH within 24 hours according to an agreed guidelines and logistics. Stool Samples will be subjected to two different kinds of tests. One of which is based on the regular detection of Fecal Occult Blood by Immunochromategraphic Rapid test [1- MAST test, from Mast Group Ltd, Mast House, Derby Road, Bootle, L20 1EA, UK and the second test utilizes the new commercially available metabolic fecal tumor [M2-pyruvate kinase (M2-PK 2 in 1 )](12,13@14) biomarker test [ScheBo, ELISA. Biotech AG, Giessen, Germany (See appendix 2)]. Indiviuals with any Positive test would be advised to undertake subsequent colonoscopy and histopathology examination for confirmatory diagnosis. A 50 individual control group of M2-PK negative tests would be invited to participate in subsequent colonoscopy and histopathology examination to look for possible false negative. The research is ongoing and our preliminary data includes the following : Total Number of Participants: 2000+ Total Number of selected Participants: 1700+ Total Number of Stool tests: 1074 Total Number of positive M2PK Test: 494 Total Number of Colonoscopies done for positive M2Pk test: 105 Percentage of participants who did the colonoscopies with positive M2PK: 21.255% Total number of Colonoscopies : 105 Positive findings (Adenomatous polyps + Tumors) : 20 Negative findings: 85 Positive Findings (20 cases): Adenomatous Polyps: 17 Adenocarcinoma (Moderately differentiated): 2 Neuroendocrine Tumor (Low Grade): 1

Oncology-2017 | by: Scientific Future Group