15th World Congress on Cancer Therapy, Biomarkers & Clinical Research December 05-07, 2016 Philadelphia, Pennsylvania, USA

Biography:

Roy is currently working in the field of cancer and gut microbiota at the National Cancer Institute (NCI), NIH in the laboratory of Dr. Giorgio Trinchieri. His main focus is to investigate the role of gut microbiota in chemotherapeutic drug and radiation therapy induced local and systemic toxicity.

Prior joining the National Cancer Institute, Dr. Roy worked at the National Institutes on Deafness and other Communication Disorders (NIDCD) in the Laboratory of Dr. Lisa Cunningham, where he contributed to the development of a sound conditioning based co-therapy, which inhibits cisplatin and aminoglycoside mediated hearing loss in mice.

Roy received his doctorate degree under the supervision of Anneliese Schrott Fischer in the field of targeted nanomedicine and hearing from University of Innsbruck, Austria in 2011

Abstract:

Anticancer chemotherapy has achieved a significant milestone in increasing the number of cancer survivors over past decades, while leaving behind the survivors with various toxic side effects, which are nephrotoxicity, ototoxicity and intestinal damage. Challenges remain to reduce systemic toxicity as well as retaining the anticancer therapy. Gut microbiota modulates cancer chemotherapy, however little is known about the role of gut microbiota in modulating systemic toxicity. We hypothesized that gut microbiota regulates systemic toxicity. Four groups (n=10/group) of 8 weeks old C57B/6 mice were treated with cisplatin, cisplatin+antibiotics cocktails (ABX), ABX only and untreated. ABX cocktail contained primaxin, vancomycin and neomycin, which depletes broad spectrum gut microbiota. This experiment was validated using C57B/6 germ free mice (contains no microorganisms). We performed anti-p-γ-H2AX and anti-ATM based DNA-double stranded break (stains foci in the nuclei) based toxicity assay in kidney and gut (small bowel). H&E and 4 color immunostaining (anti-p-γ-H2AX, anti-ATM, Actin and DAPI) were done. DNA-DSBs were evaluated using Zeiss 780 confocal and quantified by 3-D reconstruction using IMARIS. There were reductions in γ-H2AX⁺ DAPI⁺ (DNA damaged) cell populations compared to only cisplatin treated mice, indicated protection in the kidney. Both nuclear foci counts as well as the pathological scores indicated gut microbiota associated modulation in the glomeruli of kidney and in the villi of small bowel. Our data leads to a possibility to develop microbiota based therapy which might be utilized to reduce chemotherapy associated systemic toxicity and for better management of chemotherapy.

Biography:

ThaheraParveenDandu has completed her PhD at the age of 35 years from Andhra University. She is working as Deputy Manager, Formulation R&D atOman Pharmaceutical Products, Gulf based pharmaceutical company. She has published more than 9 papers in reputed journals.

Madhukiran Parvathaneni has completed his PhD at the age of 26 years from NAIP/ICAR Project, Andhra University. He is working as Senior Regulatory Associate with a global pharmaceutical CRO company. He has published more than 14 papers in reputed journals and serving as an editorial board member and reviewerfor more than 10 PubMed, Springer and Elsevier Journals.

Abstract:

Formulation of liposomes in order to enhance the oral bioavailability of phyllanthin and hypophyllanthin with proven anticancer activity. The bioactive lignans, Phyllanthin and hypophyllanthin are formulated in to conventional and PEGylated liposomes using different ratios of DSPC, DSPE-MPEG2000 and cholesterol by film hydration technique. Evaluation of the prepared liposomes was done by the determination of encapsulation efficiencies, particle size analysis, polydispersity index (PDI), zeta potential, TEM analysis, IR studies, DSC studies and powder X-RD analysis. The drug retention in vitro and pharmacokinetic properties in vivo are investigated. A new, simple and sensitive analytical method using HPLC with photodiode array (PDA) detection was developed for the determination of phyllanthin and hypophyllanthin in solvent system and in plasma.Conventional and pegylated liposomes are successfully formulated using film hydration technique with encapsulation efficiencies of 86.47%±0.13% and 83.68±0.22% (phyllanthin), 84.83±0.19% and 81.87±0.54% (hypophyllanthin). The HPLC method was successfully applied for quantification of lignans with recorded LOD and LOQ values of 56.15 ng/mL & 169.99 ng/mL (phyllanthin) and 56.04 ng/mL and 169.82 ng/mL (hypophyllanthin), respectively. From the in vivo pharmacokinetic studies, it was observed that the oral bioavailability of lignans was enhanced as indicated by AUC values of 5265.30±275.52 ng.h/mL (phyllanthin), 15217.60±987.96 ng.h/mL (conventional liposomal phyllanthin), 30810.23±2587.96 ng.h/mL (pegylated liposomal phyllanthin) and 7354.42±578.2 ng.h/mL (hypophyllanthin), 29222.4±1951.8 ng.h/mL (conventional liposomal hypophyllanthin), 58631.87±2515.46 ng.h/mL (pegylated liposomal hypophyllanthin). The developed liposomal formulations of both the lignans, showed extended drug release over 24 h in in vitro drug release studies. Pharmacokinetic studies showed the enhancement of oral bioavailability by several folds for liposomes. The enhanced oral bioavailability of lignan loaded liposomes will be helpful for the production of desired pharmacological activity relatively at a lower dose when compared to their respective free drugs.

Biography:

Nikhil M. Dongarkar,  have completed my graduation from Rajive Gandhi university of helth science bangalore and now pursuving post graduation from Parul Institute of Ayurveda vadodara, Gujarat Ayurved University.

Abstract:

In the present era when the modern thinking and the various research are taking place here is an attempt made to understand the basics of cancer in terms of Ayurveda principles. The Ayurvedic description of the pathophysiology of cancer uses traditional concepts translated into a modern context. Although the biomedical treatment of cancer is considered valuable, from an Ayurvedic perspective it results in degeneration and depletion. Taking this into consideration an Ayurvedic approach focusing on strengthening digestion, eliminating toxins, reducing tumor growth, and improving tissue metabolism is useful. An Ayurvedic approach to cancer supportive care focuses on restoring equilibrium, building strength, and rejuvenation.To understand these concept various Ayurved Classical Books and modern textbooks about cancer along with interviews were conducted with 10 experienced Ayurvedic clinicians in verbal manner. Hence on over all of this discussion it has be concluded that Ayurvedic medicine offers a unique perspective on the biomedical diagnosis of cancer that emphasizes restoring wholeness, uses natural remedies, includes a focus on emotional health, and emphasizes prevention strategies which can be a major part in pallivative and supportive care.

Biography:

Zhigang Kang has completed his PhD from University of Helsinki, Finland and Post-doctoral studies from NIMH, NIH. He is a Research Scientist in Molecular Target Core, Genetics Branch, Center for Cancer Research, National Cancer Institute and an employee of Basic Science Program, Leidos Biomedical Research, Inc., Frederick. He has been working in the field of cancer biomarkers for the past 7 years. His research interests focus on the detection of invasive tumor biomarkers include circulating tumor cell (CTC), cell free circulating tumor DNA and clinical relevance protein markers from peripheral blood of patients with various types of tumors.

Abstract:

In the study, we present a method of automated circulating cell-free (ccf) DNA isolation and digital droplet (dd) PCR-based single DNA molecule testing for detecting and typing circulating human papillomavirus (HPV) DNA. To detect single copies of HPV16 or HPV18 DNA, a digital droplet PCR (ddPCR) method was developed using the sequences of HPV16 or HPV18 E7 gene that are common amongst difference subtypes. The probes for HPV16 and HPV18 are differentially fluorescence-tagged for the simultaneous typing and quantification of both types to enhance the confidence in the tests. Two (2) different sets of primers were designed for each HPV type to produce amplicons of different length. Using ccfDNA from a few cervical cancer patients for analysis, it was apparent that the short amplicons of 70 and 88 bps gave much higher HPV copy numbers with ccfDNA than the long amplicons of 208 and 273 bps for HPV18 and 16, respectively. While the assays have maximum sensitivity of a single copy, the quantification ranges are between 10-100,000 copies of both HPV16 and HPV18 DNA which is within its linear dynamic range with coefficient of variation (CV) of less than 20% throughout the entire quantification range. To determine the spike recovery as a part of analytic validation, low amounts of known DNA template of HPV16 or HPV18 were spiked into serum samples. DNA was subsequently isolated and the purified DNA was then analyzed by ddPCR for HPV16 or HPV18 copy numbers. Approximately 75% of the spike DNA could be recovered and quantified. Thus, the HPV16 and HPV18 ccfDNA tests were specific and quantitative.

Biography:

Kara received her bachelor's and master's degrees in biomedical engineering from Drexel University in 2007. She conducted her doctoral research in the design of semi-degradable hydrogels for the repair of articular cartilage in the Biomaterials and Drug Delivery Laboratory at Drexel and in the Shanghai Key Tissue Engineering Laboratory of Shanghai Jiao Tong University. After completing her PhD in 2010, when she received the award for Most Outstanding Doctoral Graduate: Most Promise to Enhance Drexel's Reputation, she conducted research in the design of scaffolds for bone tissue engineering as a Fulbright Fellow in the Biomaterials, Biodegradables, and Biomimetics (the 3Bs) Research Group at the University of Minho in Guimaraes, Portugal. She is currently conducting research in the design of immunomodularatory biomaterials, particularly for bone tissue engineering. Her research interests include cell-biomaterial interactionns, biomaterial design, and international engineering education.

Abstract:

Background: Wound healing can be impaired by bacterial infection or patient factors including diabetes, autoimmune disease, chemotherapy, and immunosuppression. Failure to achieve complete closure of wounds, whether they are combat wounds or chronic ulcers that are commonly observed in the veteran population, leads to impaired mobility, hospitalization, amputation, and even death. The selection of an appropriate, individually tailored treatment strategy from the myriad choices available on the market is critical to successful wound healing. Unfortunately, there is no accurate, objective way to determine if a wound is healing or not.  

For example, in clinical practice, chronic diabetic ulcers that fail to show a 40% reduction in surface area (length x width) over 4 weeks are considered non-healing. However, this method of healing diagnosis has low accuracy (~60%) because these assessments are subject to error, can differ from one physician to the next, and convey only superficial characteristics of the wound. As a result, patients are treated with ineffective treatments for far too long (leading to amputation or death), or expensive therapies like synthetic skin substitutes and hyperbaric oxygen therapy are used when they are not necessary (causing waste to our healthcare system).

Therefore, we developed a quantitative molecular assay that uses debrided wound tissue that would otherwise be discarded to evaluate the behavior of wound macrophages, the inflammatory cells recognized as the major regulators of healing, in order to determine if a wound is on a healing trajectory or is likely to develop complications and fail to heal.

Methods: In the pilot study, debrided wound tissue, collected during routine wound care that would otherwise be discarded, was collected from the ulcers of 21 diabetic patients over 4 weeks. Treatment and follow-up were conducted for an additional 8 weeks to determine if the ulcer had completely healed at 12 weeks. Gene expression data of a panel of 7 biomarkers related to the behavior of macrophages was converted to a single score that is indicative of the inflammatory status of the wound. Briefly, the score represents a ratio based on the M1/M2 paradigm of macrophage behavior, in which M1 macrophages are inflammatory yet initiate the healing process, while M2 macrophages are anti-inflammatory and facilitate resolution of the healing process. Non-healing wounds are believed to be stalled in the M1 phase.

Results: In the pilot study of 21 patients with diabetic ulcer, the M1/M2 score decreased over a 3-week period for all wounds that ultimately healed by 12 weeks of treatment (n=9 patients). In stark contrast, the scores stayed the same or increased for all wounds that ultimately failed to heal (n=12 patients). In fact, the fold change in the score at 4 weeks from the initial visit was almost 100 times higher for nonhealing wounds compared to healing wounds (p<0.0001). Using a 4-week fold-change cutoff of 1 (so that an increase was used to classify non-healing wounds and a decrease was used to classify healing wounds), the score successfully predicted healing or nonhealing in 19/21 patients in this study (100% positive predictive value, 83.3% negative predictive value, and 90% overall accuracy). Interestingly, healing wounds generally had higher M1/M2 scores than non-healing wounds at the start of the study, suggesting that inflammation is critical for wound healing and that with further optimization, analysis of a single sample may be predictive of likelihood of developing wound complications.

Conclusions: These results indicate that analysis of wound tissue that would otherwise be discarded can be used as a quantitative, accurate indicator of healing. Such an assay will be critical for employing a precision medicine approach to wound care.

Next steps: More patients are needed to further optimize this diagnostic assay. Wound samples can be stored in a buffer and shipped at room temperature to our lab for analysis. If you are interested in collaborating on this project.

Future directions include expanding to other wound types (combat wounds, burns, chronic venous ulcers, etc.) and developing a rapid assay for point-of-care diagnosis. Our pilot data suggest that this method will be readily applicable to burn wounds without the need for further optimization.

Citation: Nassiri, S., I. Zakeri, M.S. Weingarten, K.L. Spiller. “Relative expression of pro-inflammatory and anti-inflammatory genes reveals differences between healing and nonhealing human chronic diabetic foot ulcers.” Journal of Investigative Dermatology 2015 (135) 1700-1703.

Biography:

Abstract:

Biography:

Nalinee Sripaung has completed her PhD from Tokyo Medical and Dental University, Japan. She is the Assistant Director of Bureau of Occupational and Environmental Diseases, Department of Disease Control, Ministry of Public Health, Thailand. She has experience working with the Thai National Chemicals Management Strategy for prevention and control of occupational and environmental diseases. She has published more than 30 papers in chemicals dissemination and reputed journals and has been serving as an Editorial Board Member of reputed journal in Thailand.

Abstract:

According to the type of metabolites in blood and urine acting as the biomarker, the concentration of biomarker acts as the indicator for health risk assessment. The health risk management, concerning with chemical toxicity, faces the problem of how to use the concentration of biomarker to be the suitable indicator for health risk assessment. Presently, there is no safety value adjustment of health risk assessment for people’s health in community. Therefore, the field of prevention and control of occupational and environmental diseases has to use the safety value of biomarker concentration for worker’s health to be the safety value for people’s health indicator in community for health risk assessment resulted from chemical pollution. The study of using the safety value of worker’s health to identify people’s health in community in case of health surveillance of chemical incidents was proceeded during the year 2015-2016. It was found that biomarkers concentrations of VOCs (Volatile Organic Solvents) of worker’s health were higher than the actual baseline chemicals exposure of People’s health in community. The result from the adjustment of the risk group of people in community by worker’s health safety value indicated the lower amount of people than the actual amount risk group. Thus, the baseline concentration of biomarker should be further studied to be the health surveillance value for people’s health risk assessment caused by chemicals toxicity.

Biography:

Mohammad Reza Hashempour has completed his Doctorate from Army University of Medical Sciences and Postdoctoral studies in Surgery from Golestan University School of Medicine. He has published papers in reputed journals.

Abstract:

Pleural effusion is one of signs and complications resulting from malignant diseases such aslung and breast cancer, and also tuberculosis and infective lung disease. Diagnostic evaluationfor patients with pleural effusion include history, physical exam, chest x-ray and if necessarythoracocentesis and cytologic analysis of pleural fluid. According to cytologic evaluation ofpleural fluid, pleural effusion divide in two group: exudative and transudative, that exudativepleural effusion require more diagnostic evaluations. By cytologic analysis of pleural fluid wecan use of tumor markers and other biomarkers to better diagnose malignant pleural effusion. Inthe previous studies  by using immunochemical approach, interleukin-17 and also CEA expressin more amounts in malignant pleural effusion than in benign pleural effusion, in contrast tointerleukin-27. In this study we examined the concentration of Interleukin-27 & 17 in PleuralFluid with Causes of Exudative Pleural Effusion in the Patients Referred to educational Hospitalof Gorgan of Iran in 2015-16. This is a descriptive-analytical and case-control study and 130patient with exudative pleural effusion were enrolled in the study after an informed consent.Samples collected from the  patients divided  in  two main  group including   88 patients withmalignant pleural effusion and 42 patients with benign pleural effusion. In next step by using ofthe same previous pleural fluid samples, the concentration of Interleukin-27 & 17 was measuredwith ELISA by an specific Kit. After entering to computer through SPSS-18 statistical software,description of data was done into frequency and percentage. Interleukin-27 concentration was(203.05±76.03)   in   patients   with   malignant   causes   and   (344.15±236.42)   in   benign   causesspecially tuberculosis. Interleukin-17 concentration was (69.73±64.58) in patients with malignantcauses and (55.32±43.60) in benign causes.The results showed that these difference werestatistically significant (p=0.000 for IL27) and  (p=0.02  for IL17). In other word  interleukin-27level, is higher in the benign pleural effusions and interleukin-17 level, is higher in the malignantpleural effusions. According to higher levels of interleukin-27 in benign  pleural effusions  andhigher level of interleukin-17 in malignant pleural effusions, maybe we can achieve importantresults in differentiating between malignant and non-malignant pleural exudate, without the needfor invasive procedures, by putting together the clinical symptoms, the interleukins concentrationin pleural fluid and pleural fluid cytology results.

Biography:

After completing her doctoral degree from the School of Life Sciences at Jawaharlal Nehru University, New Delhi, India, Dr. Ghosh continued her training in molecular biology at the National Institutes of Health (NIH/NICHD), Bethesda, MD, where her work dealt with the mechanisms that regulate cellular DNA replication during animal development. Her focus then shifted to development of sequencing-based assays to support clinical decision making in cancer therapy and management, an area she pursed as a molecular geneticist at the Sidney Kimmel Comprehensive Cancer Center in Johns Hopkins Medical Institute. Currently, Dr. Ghosh is a regulatory scientist at the FDA where she is actively involved in the review and approval of companion diagnostic devices.

Abstract:

An important requirement in the development of targeted therapies is identification of clinically relevant biomarkers, such as DNA mutations or protein overexpression. The detection of appropriate biomarkers is essential for the safe and effective use of targeted therapies and serves as the basis for development of companion diagnostic devices. There are several regulatory considerations for successful biomarker-targeted therapy-companion diagnostic co-development programs. My talk will highlight challenges and opportunities associated with these programs.

Biography:

Has degree in Dentistry from the University of San Martín de Porres (USMP - 2012), with experience in General Practice with emphasis in the area of Surgery and Traumatology Maxillo-facial, performed stage in Surgical of Specialized Clinical Center for Dentistry, USMP (2013). Currently, he participates in the Oral Surgery Clinic at the Faculty of Dentistry of the University of Sao Paulo - Brazil (USP) of the Department of Surgery and Prosthesis Maxillofacial Facials; He presents proficient in Portuguese and English as a foreign languages. Nowadays, he develops the academic master's in Nuclear Technology Program - Area of concentration materials at the Institute of Energy and Nuclear Research (IPEN), São Paulo Brazil, Lasers and Applications Center (CLA).

Abstract:

Introduction: Clinical Radiotherapy is extremely important for the treatment of malignant lesions of the head and neck region, however, exposure to ionizing radiation can lead to systemic or local complications during and after radiation treatment. Among these immediate local complications, it stands out in the oral cavity xerostomia and the consequent decay of radiation. Regarding late complications produced by radiation, oral mucositis and osteoradionecrosis are included, which are considered dose-dependent lesions, with high incidence in recent decades (1-30%) and unwieldy, although these are presented after completion of treatment and under the influence of local factors. Methodology: The methodology proposed in this study is to analyze the effect of gamma radiation after irradiation of the samples, using the dose rate used in patients suffering with head and neck cancer. The samples were obtained from human enamel and root dentin; and swine mandibular bone, which were previously polished, and then submitted to the analysis of the initial surface microhardness of all groups. Subsequently, the samples were irradiated in a dose rate of 2 Gy per day, completing a total dose of 72 Gy. Finally, the samples were submitted to analysis of surface microhardness after irradiation, and the morphological analysis on the SEM. Results and discussion:  The data were analyzed statistically with a significance level of 95% (p <0.05%). Conclusion: From the preliminary results of the surface microhardness of the samples, it was founded a marked loss of hardness in the root dentin, mandibular body and retro-molar region.

Biography:

Gao Fei is a PhD student in the University of Hong Kong. His major is Chinese Medicine. His  researh interest contain the traditional Chinese herbs processing method and the targeting delivery system by advanced nano-tech. He has publicated more than 30 papers in English and Chinese , which mainly focus on the Traditional Chinese Medicine.      

Abstract:

To improve the poor delivery of Isoliquiritigenin (ISL), a natural anti-breast cancer compound, is essential to promote therapeutic outcome. Herein, a tumor-targeting lipid-polymer hybrid nanoparticle (NP) system modified by tumor-homing iRGD peptides has been developed to enhance ISL anti-breast cancer efficacy. The hybrid NPs were prepared by a modified single-step nanoprecipitation method to encapsulate ISL. By the preparation aspect, iRGD peptides were anchored on the surface by a post-insertion method (ISL-iRGD NPs). The stable lipid-polymer structure of ISL-iRGD NPs with high encapsulation and loading efficiency has been confirmed. By the pharmacological research aspect, the enhanced anti-breast cancer activity of ISL-iRGD NPs was conducted both in vitro and in vivo. Compared to free ISL and non-iRGD modified counterpart, ISL-iRGD NPs showed higher cytotoxicity and cell apoptosis against three types of breast cancer cells. In addition, it would attribute to the higher cellular accumulation mediated by the iRGD-integrin recognition and nano-scale effect. More importantly, based on the active tumor tissue accumulation by iRGD peptides and the prolonged in vivo circulation by the stealth nano-structure, ISL-iRGD NPs displayed higher tumor growth inhibition efficiency in 4T-1 bearing breast tumor mice models. All in all, the constructed iRGD modified lipid-polymer hybrid NPs would provide a promising drug delivery strategy to improve ISL anti-breast cancer efficacy.

Biography:

Tamar Giorgadze is a Scientist at the department of biological systems of physics, Andronikashvili Institute of Physics. She has completed her PhD at the age of 30 years from St. Andrew The First-Called Georgian University of The Patriarchate of Georgia. She is author of 9 scientific publications.

 

Abstract:

The goal of this work is using the method of laser - induced fluorescence resonance energy transfer (FRET) of electronic excitation in the donor-acceptor pair of intercalators, (acridine orange as a donor and ethidium bromide as an acceptor), for quantitative analysis of the quality of DNA double helix. The approach allows getting a visual picture of the defects of genetic apparatus of tissue cells, particularly of skin cells in real time and it can be used for diagnosis of skin diseases, also in cosmetology.

Transition metal ions such as Cu(II), Cu(I), Ag(I), silver nanoparticles (AgNPs), photo- and thermo effects were used to cause double helix defects in DNA.

Concentration of DNA sites, which are applicable for intercalation, after the exposure to Cu(II), Cu(I), Ag(I) ions, AgNPs impact as well as laser irradiation (λ = 457 nm) and temperature, which are applicable for intercalation, were estimated in relative units.

The nanoscale FRET method allows estimation of the concentration of double helix areas with high quality stability applicable for intercalation in DNA after it was subjected to stress effect. It gives the opportunity to compare DNA-s of 1) different origin; 2) with various damage degrees; 3) being in various functional state.

Biography:

Adewale holds an MBBS degree from University of Ilorin, Nigeria, and MSc in Biochemistry from the University of Kent, UK.  While waiting to start his PhD later in the year at the University of Manchester, UK, he currently lectures in the Department of Biochemistry, Osun State University, Osogbo, Nigeria. He has 4 publications in reputable journals.

Abstract:

Despite significant advances, neuroblastoma remains one of the most difficult childhood cancers to cure, with less than 40% of patients with high-risk disease being long-term survivors. Resistance acquisition to chemotherapy is a major cause of treatment failure in high-risk cases. Here, we tested the effects of novel palladium-based (SW005c, SW009b, SW012a, SW017a and SW018a) compounds on the viability of the human neuroblastoma cell line UKF-NB-3 and its sub-lines adapted to the clinically approved platinum drugs cisplatin (UKF-NB-3^rCDDP¹⁰⁰⁰), carboplatin (UKF-NB-3^rCARBO²⁰⁰⁰), and oxaliplatin (UKF-NB-3^rOXALI²⁰⁰⁰) by MTT assay. The palladium compounds SW005c, SW009b, SW012a, SW017a, and SW018a interfered with the viability of the cells in low micromolar concentrations (1.4µM – 4µM). Although some degree of heterogeneity in the response of the cell lines to the palladium compounds was observed, in particular with regard to SW017a and SW018a, there was no pattern indicating that acquired platinum drug-resistance would be associated with decreased sensitivity to the investigated palladium compounds. This suggests that the anti-cancer mechanism of action of the palladium compounds differs from that of the approved platinum drugs. In conclusion, the newly synthesised palladium-based compounds should be further studied in additional cell line models and animal experiments.

Biography:

Shujun Huang is a PhD student at the University of Manitoba. She works on bioinformatics and cancer signatures. She has strong interests in cancer prognosis and personalized treatment. She also has three years’ industrial experiences in a genetic testing company in China about personalized medicine and disease risk assessment. She has published 9 papers in Chinese and English journals.

Abstract:

Background: Breast cancer is a heterogeneous disease and the personalized medicine is the hope to improve the clinical outcome. Multi-gene signatures have been extensively studied for breast cancer stratification in the past decades and more than 30 different signatures have been reported. One argument about these signatures is that there are little overlapped genes among the reported signatures. We investigated the breast cancer signature genes to proof our hypothesis that the genes of different signature may share the common functions, and we further tried to use these previously reported signature genes to build better prognostic models.

Methods: A total of 33 signatures and the corresponding gene lists were investigated. We first examined the gene frequency in these signatures and the gene overlapped. Each signature gene list was analyzed by the KEGG pathways and gene ontology (GO) terms with a p-value of 0.1 cutoff and the functional groups were compared among all signatures. The common genes were tested for breast cancer subtype classifier using the METABRIC (Molecular Taxonomy of Breast Cancer International Consortium) data. The common genes were also tested for building the Yin Yang gene expression ratio (YMR) signature using public datasets (GSE1456 and GSE2034).

Results: There were only 238 of the total 2239 genes that were overlapped in at least two signatures while 429 of the total 1979 function terms were common in at least two signatures. As we expected, most of these common function terms involve in cell cycle process. Interestingly, though have almost no overlap genes, the signatures used for ER-positive (e.g. OncotypeDx) and the signatures used for ER-negative (e.g. basal signatures) have the common function terms of cell death, regulation of cell proliferation, response to organic substance, intracellular signaling cascade, response to hormone stimulus, response to oxygen levels, bone development, DNA packaging, response to hypoxia, ossification and skeletal system development etc. We used the 62 genes that were common in at least three signatures as classifier and subtyped the 1141 METABRIC data including 144 normal samples into 9 subgroups. These 9 subgroups showed different clinical outcome. Among the 238 common genes, not all were differently expressed between tumor and normal tissues. We selected those genes that are higher expressed in normal then in tumors (21 Yang genes) and those higher in tumors than in normal (72 Yin genes) and built the YMR model signature. This YMR showed significance in risk stratification in the two datasets (GSE1456 and GSE2034).

Conclusions: The debate that no overlap genes among most breast cancer signatures can be partially explained by our discovery that these signature genes represented the similar functions though they are different genes. The genes extracted from these previously reported signature is a good resource for new model development. The subtype classifier and YMR signature built from the common genes showed promising result.

Biography:

Safana Salim Al Saidi graduated from college of medicine, Sultan Qaboos University, Muscat, in 2003. Then I have started my job as a medical doctor since then. In 2006, I joined an Oman Medical Specialty Board (OMSB) to do my specialty in Clinical Biochemistry for 6 years. Graduated from the Board in 2014 and worked as Chemical Pathologist since then. I got my FRCPath part 1 in 2010. Right now, I have finished all the components on FRCPath part 2 and waiting for the official certificate from the Royal College of Pathologists to be a fellow, which will be on 15 September. 2016. I have two publications.

Abstract:

Background and objectives: Prostate cancer is the leading cancer in older men. When prostate cancer is detected early (organ defined), it is potentially curable by radical prostatectomy. As per the Ministry of Health (MOH) Oman Cancer Incidence Registry, cancer of prostate is the second most common cancer (in males) and seventh most common cancer (in both males and females), with 57 cases were diagnosed in 2011. Therefore, early detection is important and prostate-specific antigen (PSA) is widely used as a laboratory test for this purpose. However, despite its wide use, its value in screening men particularly asymptomatic is controversial particularly in term of risks and benefits of early detection.

Methods: This is an observational prospective study that included 136 male patients aged (mean ± SD 67± 8.89; range 45-90) who were scheduled for prostate biopsy in two different tertiary care teaching hospitals in Muscat, Oman. Blood specimens from these patients were collected at the same setting before obtaining the prostatic biopsy; the sera were stored at -200C until analysis. Laboratory measurements of the three prostate-specific antigen (PSA) markers (tPSA, fPSA and [-2]proPSA) were processed using UniCell DxI 600 Access Immunoassay System (Beckman Coulter, USA). Calculation of Prostate Health Index (phi) using Access Hybritech phi® software was performed too. The histopathological report of the prostatic biopsy for each patient was obtained from the Histopathology Laboratory of the concerned hospital along with the clinical and laboratory data through the Hospital Information System (HIS).

Results:

The study showed that phi has the best validity markers as compared with other prostate markers. It gave sensitivity and specificity of 82.1% and 80.6 % respectively with AUC of 0.81 at cutoff value of 41.88. The remaining prostate markers showed sensitivities and specificities of 78.6% and 25.9% for tPSA; 35.7% and 92.6% for %fPSA; 64.3% and 82.4% for % p2PSA: and 75% and 35.2% for age-adjusted tPSA respectively. Their AUCs at the best cutoff values were 0.67 at 10.1 µg/L for tPSA; 0.70 at 11.6% for %fPSA; 0.55 at 1.4% for %p2PSA; and 0.50 for age-adjusted tPSA.

Conclusion:

The study has proved the usefulness of phi and its component assays in predicting the diagnosis and prognosis in men who are suspected of having prostate cancer. The use of phi outperforms other conventional prostate markers; tPSA and fPSA, when used alone or in combination. Phi appears to be more accurate than tPSA and fPSA in terms of excluding prostate cancer before biopsy, hence it helps the physicians to avoid unnecessary biopsies, particularly in patients with gray zone tPSA level. Phi is the strongest marker that also correlates proportionally with Gleason Score; therefore it is also useful in predicting the aggressiveness of the disease.