Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 5th World Congress on Cancer Therapy Atlanta, Georgia, USA.

Day 1 :

Keynote Forum

Jack C. Westman

University of Wisconsin School of Medicine and Public Health, USA

Keynote: A Review of Cancer Immunotherapies and Nutritional Therapies

Time : 08:50-09:15

OMICS International Cancer Therapy 2015 International Conference Keynote Speaker Jack C. Westman photo
Biography:

Jack C. Westman completed an M.D. and an M.S. at the University of Michigan. He is an Emeritus Professor at the University of Wisconsin School of Medicine and Public Health. He has published more than 160 professional articles and 12 books. He has served as president of three professional organizations and currently is the president of Wisconsin Cares, Inc..

Abstract:

Immunotherapies and nutritional therapies are assuming prominence in the prevention and treatment of cancer. \\\\r\\\\n\\\\r\\\\nImmunoediting is the process in which aberrant cells multiply. Immunosurveillance by the immune system distinguishes between aberrant and normal cells and usually eradicates aberrant cells. Some aberrant cells withstand immunosurveillance and may become benign tumors. Some aberrant cells grow unrestrained by immunosurveillance and become cancer cells in the neoplastic process. Immunotherapies can be classified as: 1) active that stimulates a patient’s innate immune response; 2) adoptive that exposes immune system cells to specific cancer antigens; 3) restorative that restores deficient functions of immune system cells without removing them from a patient; and 4) passive that infuses a patient with antibodies to antigens on the patient’s cancer cells. The evidence suggests that a combination of immunotherapies most closely resembles the way in which the immune system works. By 2013, thirteen immunotherapy antibodies had been approved by the FDA, and many more are currently being evaluated in clinical trials.\\\\r\\\\n\\\\r\\\\nNutritional therapies include 1) the ketogenic diet that starves cancer cells; 2) CELLFOOD that produces an alkaline body and high levels of oxygen that smother cancer cells; 3) curcumin that inhibits tumor growth and metastasis; 4) IAHCC that is an immune system modulator, 5) milk thistle that stimulates detoxification pathways and inhibits the growth of cancer cells; and 6) vitamin D3 that can prevent the formation of and kill cancer cells. The most effective approach is to use all of them as a “cocktail”.\\\\r\\\\n

Keynote Forum

Erwin G Van Meir

Emory University,USA

Keynote: BAI1 is a brain-specific tumor suppressor

Time : 09:15-09:40

OMICS International Cancer Therapy 2015 International Conference Keynote Speaker Erwin G Van Meir photo
Biography:

Dr. Van Meir has completed his PhD from the University of Lausanne, Switzerland and postdoctoral studies from the Ludwig Institute for Cancer Research, La Jolla, CA. He is the leader of the cancer cell biology program at the Winship Cancer Institute, an NCI-designated Cancer Center. He has published over 150 manuscripts in peer-reviewed international journals and these have been cited over 15,000 times

Abstract:

Brain-specific Angiogenesis Inhibitor 1 (BAI1) is a seven transmembrane G protein-coupled receptor (GPCR), and we have previously shown that it has potent anti-angiogenic and anti-tumorigenic properties in gliomas.1-6 We now found that BAI1 expression is reduced in human medulloblastoma (MB) by epigenetic mechanisms, involving methylated DNA binding protein MBD2 and histone methylase EZH2. Restoration of BAI1 expression reduced MB cell proliferation and tumor growth in mice xenografts. Targeting MBD2 and EZH2 with small molecules reactivated BAI1 expression, and suppressed tumor growth, supporting the use of epigenetic therapeutics against MB. To more directly examine whether loss of BAI1 expression may favor tumor development during cerebellar development, we generated a Bai1 knockout (KO) mouse.7 We detected a thicker external granular layer (EGL) during early postnatal cerebellum development, which was accompanied by increased proliferation in cGNPs and aberrant activation of Sonic hedgehog signaling. Bai1 loss was not sufficient to initiate tumorigenesis per se, but dramatically accelerated MB tumorigenesis when crossed to mice heterozygous for patched 1 (ptc1+/-), and we will present some of the underlying mechanisms. Altogether, our findings provide insight into the physiological function of BAI1 in the brain, in particular the suppression of medulloblastoma formation in the cerebellum.

OMICS International Cancer Therapy 2015 International Conference Keynote Speaker Yoshiaki Omura photo
Biography:

Abstract:

Introduction: Non-invasive, quick diagnosis of cancer and their safe, effective individualized treatment will be presented. Methods:Using simple, non-invasiveElectro-Magnetic Field Resonance Phenomenon between 2 identical molecules which received a U.S. patent in 1993, we analyze completed Mouth, Hand, and Footwriting Form, to detect most malignancies & their metastasis at any part of the body long before standard laboratory tests can detect any malignancies. For treatment, before using any treatment, we used an average adult optimal dose of 400 I.U. Vitamin D3. Our latest discovery is diagnosis of cancer from the QRS complex of an ECG.Results: We treated over 100 patients, most of them who had a significant reduction of cancer parameters, including Oncogen C-fos Ab2 &Integrin α5β1 (to less than 1/1000), and 8-OH-dG (which is proportional to DNA mutations to 1/5~1/10). If Integrinα5β1 is less than 100 ng, standard laboratory tests often cannot detect a malignancy. The most optimal, effective dose of any treatment was individually determined by using above method. Average optimal dose of Vitamin D3400IU for adult not only inhibit cancer activity markedly but also often increased extremely low Acetylcholine and DHEA levels to normal level. Cancer activity & associated symptoms significantly reduced without any side effects in more than 85% of patients. However, commonly used 2000~5000IU Vitamin D3 significantly promote cancer activities more than 2 times.Discussion: In the remaining 15% of patients we found that what patients were eating, drinking, and wearing affected their treatment. Since most patients made significant improvements, before using any other cancer treatment, we recommended to see the result of initialoptimal dose of Vitamin D3treatment. We found the optimal dose also depends on their age & the degree of patients physical activity, while standard methods of estimating dose requirements are proportional to body weight.

Keynote Forum

Michael Weber

Laser Clinic Dr. Weber, Germany

Keynote: Systemic and interstitial photodynamic laser therapy: New options in oncology

Time : 10:15-10:40

OMICS International Cancer Therapy 2015 International Conference Keynote Speaker Michael Weber photo
Biography:

Michael Weber is a medical practitioner for more than 20 years in Germany and leader of three medical centers for general and internal medicine, pain and cancer treatment.rnFurthermore he is a certifi ed bio-chemist and medical doctor. He is working in research with many national and International institutions and universities. He is president of thernInternational society for Medical Laser applications and editor in chief of the Inter-national Journal for Medical Laser Applications. He is also Co-editor of several other journals.

Abstract:

Photodynamic therapy is one of the most interesting and promising approaches in the treatment of various cancers. Treatmentsrnare easy to perform and – in contrast to chemotherapy – normally without severe side-eff ects. Th e principle is the stimulationrnof a light-sensitive drug which is injected into the blood. Th rough endocytosis, the photosensitizer binds to tumour cells anywherernin the body with high specifi city. Th e process takes several hours and tumour cells will have turned light sensitive at the end.rnTumour tissue is subsequently destroyed by irradiation with light of appropriate wavelength according to the absorption spectra ofrnthe various photosensitizers. Th e basic principle behind this mechanism is the development of radical oxygen species.rnIn contrast to traditional chemotherapy PDT does not only destroy cancer cells by oxygen radicals but also initiates a lotrnof diff erent reactions in the treated area with a stimulation of the immune system (PDT-immunisation). Photosensitizers arernmostly porphyrin molecules and derivatives either from the human heme (without the iron atom) or plantderived chlorophyllrn(without the magnesium atom). Accordingly, they are called hematoporphyrins or chlorines. Some are already approved and usedrnin therapy, e.g. Photofrin for treatment of early stage bronchial and gastric cancer.rnRed (in most cases), blue or yellow light is used for light activation of photosensitizers either from outside or through anrnendoscope. Due to the limited penetration depth of light eff ective photosensitizer stimulation and tumour destruction can onlyrnbe achieved at the surface of the skin or in the tissue just a few centimetres underneath the skin. An eff ective treatment of deeprntumours or metastases (e.g. liver cancer or lymph nodes) has normally not been possible and therapeutic applications have so farrnbeen primarily used to treat dermatological tumours. Due to this limitation, progress has been slow until recently.rnToday, new technological developments that facilitate systemic and interstitial photodynamic therapies overcome this barrierrnand constitute the basis for massive growth in the fi eld. Th e lecture will focus on presenting the new technology of systemic andrninterstitial photodynamic laser therapy, newest photosensitizers (with very specifi ty and low side-eff ects) and clinical results fromrnthe last few years of research and development in Germany.

  • Cancer Cell Biology Diagnosis & Applied Research
    Organ-Specific Cancer
    Advances in Malignancy Counteractive Action and Screening
Speaker

Chair

Yoshiaki Omura

New York Medical College, USA

Speaker

Co-Chair

Fereydoon Family

Emory University, USA

Biography:

Yoshiaki Omura received both Oncology Residency Training and a Doctor of Science Degree through research on Pharmaco-Electro Physiology of Single Cardiac Cells in vivo and in vitro from Columbia University. He has published over 250 articles and 7 books. He is Executive Editor of Integrative Oncology & Editorial Board Member of Journal of Clinical Trials in Cardiology, etc. Using his new diagnostic method, which received U.S. patent, he can non-invasively and rapidly measure many neurotransmitters, other chemicals, asbestos, viruses, and bacteria. He developed a non-invasive, quick diagnostic methods of malignancies, as well as a method of evaluating the effects of any treatment.

Abstract:

Introduction: Recently the author found that using ECGs, various cancers at diff erent organs can be detected. Method: From recorded ECGs, cancer was detected using Electro-Magnetic Field Resonance Phenomenon between 2 identical molecules or 2 identical molecular information, i.e. between specifi c cancer microscope tissue slides and rapidly changing part of QRS complex of ECG using this U. S. patented method. Result: Using ECGs, the author was able to detect various cancers including lung, esophagus, breast, stomach, liver, pancreas, colon, uterus, ovary, prostate gland, common bone marrow related malignancies, etc. Th e author was also able to fi nd when the patient has more than one diff erent cancer at diff erent parts of body. Also, most of drugs taken within 10 hours before taking ECG can be detected from rapidly changing part of QRS complex. Among 50 ECGs of various cancer patients without knowing diagnosis, 2 patients with different diagnosis were found from ECGs and later diagnosis from ECG was found to be correct. In 3 cancer patients, additional cancers were also detected from ECGs. Discussion: The therapeutic effect of specifi c cancers can be evaluated from ECGs. If ECGs is taken periodically, we can find approximately when cancer information starts appearing in the ECGs. This new method can be applied for detection and screening of any cancer. Consequently, ECGs can not only provide information on the heart but also detect any single cancer or multiple cancers existing in the same individual. ECGs can be used to reveal undetected cancers or misdiagnosed cancers as well as detection of medication patient is taking.

Biography:

Jayalakshmi Sridhar has completed her PhD at the age of 30 years from Osmania University, India and postdoctoral studies from Georgetown University, University of California-Riverside and Xavier Uniersity of Louisiana. She is presently an assistant professor at Xavier Uniersity of Louisiana. She has published more than 27 papers in reputed journals and has two patents.

Abstract:

In 2013, the number of new cases of breast cancer in the US was 234, 580 and ~1.7 million worldwide. Despite the advances in early detection and treatment of breast cancer, about 30% of patients with early stage breast cancer have recurrent disease where resistance to therapy is common and expected. HER2 is overexpressed in 20-40% of invasive breast cancer, and 12-24% of these patients develop resistance within 6 months for the widely used therapy trastuzumab. HER2 oncogenic variant HER2 16 has been shown to promote receptor dimerization, cell invasion and also trastuzumab resistance of NIH3T3 and MCF-7 tumor cells lines. We have identifi ed several naphthoquinones that show growth inhibition of the MCF-7 HER216 cell lines with a signifi cantly higher potency than the present clinically used tyrosine kinase inhibitor lapatinib. Th ese compounds also inhibit auto-phosphorylation of the Y1248 and Y1068 residues of HER2 and EGFR, respectively.

Biography:

Fereydoon Family holds the Samuel Candler Dobbs Chair of Physics at Emory University. He has published over 200 scientifi c articles and seven books. His contributions in the study of pattern formation, particularly dendritic solidifi cation, which is commonly known as the “The Snowfl ake Problem”, has been widely featured in the media including the New York Times, CBS News, CNN, PBS, Physics World, and James Gleick’s popular best selling book “Chaos”. His most widely cited work is known as the Family-Vicsek Scaling that for over two decades has formed the basis for investigations of kinetic roughening of surfaces and interfaces in thousands of publications in many fi elds of science and engineering. Professor Family is an elected Fellow of the American Physical Society and the recipient of many honors and prizes, including the Lawton-Plimpton Prize, the Jesse Beams Prize from the American Physical Society Southeastern Section for outstanding research, as well as the Williams Distinguished Teaching award for excellence in teaching.

Abstract:

Sections of patient tumors of gliomas grades II-IV, stained with an antibody specifi c to the mutated IDH1 protein, were analyzed using a mathematical image analysis technique. We calculated the glioma cell distributions in these slides and compared the cell distributions in the invasive front with diff erent tumor types and grades. Our approach provides strong evidence that higher grade gliomas have more diff used invasive fronts.

Horacio Rilo

North Shore LIJ Health Systems, Hofstra University, USA

Title: Exosomes in the treatment of pancreatic adenocarcinoma

Time : 12:20-12:40

Biography:

Horacio Rilo is a Professor of Surgery at Hofstra University and Director of the Pancreas Disease Center at North Shore LIJ Health Systems in New York. His research focuses is translational medicine with a specifi c emphasis on cellular therapy for pancreatic diseases. Rilo has one of the largest world experiences in islet cell transplantation for the treatment of unremitting pancreatitis and Type 1 Diabetes.

Abstract:

Pancreatic cancer (PaCa) is one of the most aggressive and lethal malignancies, with an annual incidence and mortality rate that is nearly identical. It is considered one of the deadliest cancers and ranks fourth in cancer related mortality. Poor prognosis for PaCa is primarily attributed to late detection and early metastasis. Th ese cancers respond poorly to chemotherapy and radiation, and surgical resection remains the standard treatment. Unfortunately, the 5-year survival rate for the earliest form of PaCa (Stage IA) is 14% and only 1% for Stage IV. PaCa diagnosis currently involves endoscopy, cross-sectional imaging and cytological examination of pancreatic fl uid, methods that are either invasive or expensive. Diagnostic tests that are sensitive, specifi c, and capable of early diagnosis are needed and could signifi cantly improve pancreatic cancer treatment and outcomes. Recently, exosomes, extracellular vesicles containing microRNAs (miRNAs), mRNA, and protein, have been used as pancreatic cancer markers. miRNAs are non-coding RNAs that play a role in the regulation of post-transcriptional gene expression. Importantly, the miRNA expression profi le of tumor-derived serum exosomes in PaCa patients diff ers signifi cantly from those of healthy people as well as those with non-malignant disease. Further, it is thought that patients suff ering from cancer have exponentially higher numbers of circulating exosomes since they are secreted in large amounts during carcinogenesis. Finally, exosomes released from tumor cells are readily detected in body fl uids, thereby providing a potentially non-invasive diagnostic tool that would enable the earlier diagnosis of pancreatic cancer and potential improvement of outcomes.

Biography:

Singal joined the UAB as an Assistant Professor in the Division of Gastroenterology and Hepatology of the Department of Medicine after completing Masters in Clinical Research from UTMB Galveston TX, and AASLD sponsored advanced fellowship in Transplant Hepatology at the Mayo Clinic, Rochester, MN. Singal is active in the Faculty practice with clinical and translational research interests of steatohepatitis (due to alcohol use as well as due to non-alcohol fatty liver disease), simultaneous liver-kidney transplantation, and porphyria cutanea tarda.

Abstract:

This lecture will address the inappropriate use of CT or MR scan for hepatocellular cancer (HCC) screening in patients with cirrhosis. American Association for Study of Liver Diseases recommends Ultrasound (USG) for HCC screening in cirrhosis. CT/MRI is used to confi rm HCC when suspicious lesions are noted on the US examination. However, CT / MRI scan is oft en inappropriately used for screening in routine clinical practice. In this presentation, we would discuss and share data on the inappropriate use of CT or MR scans as analyzed using the SEER-Medicare Linked Database with fi les containing 100% HCC cases, 5% cases of other cancers and 5% non-cancer Medicare benefi ciaries. Using the study cohort of cirrhotics with HCC aged 67 yrs. or more at the time of diagnosis and with complete Medicare enrollment, CT/MRI done between 6 and 12 mo. before HCC diagnosis was classifi ed as inappropriate if the scan was done without claim for symptoms on CT/MRI or for HCC diagnosis and without US examination within 6 months prior to CT/MRI scan. Of all cirrhotics in this Medicare population, only 4% received screening and 30.6% of CT/MRI was done inappropriately. Apart from increasing health care cost, inappropriate CT/MRI also puts patients at risk for radiation exposure. Studies are needed for strategies to improve rigorous adherence to HCC screening and also identify high risk patients which may benefi t from use of CT/MRI.

Break: Lunch Break 13:00-13:30 @ Restaurant

Soumen Paul

University of Kansas Medical Center, USA

Title: Atypical PKC signaling and breast cancer metastasis

Time : 13:30-13:50

Biography:

Paul has completed his PhD from Calcutta University and postdoctoral studies from University of Wisconsin School of Medicine and Public Health. He is an Associate Professor and the Director of the Garduate Program within the Department of Pathology & Laboratory Medicine at the University of Kansas Medical Center. He has published more than 30 papers in reputed journals and has been serving as an editorial board member of the journal Scientifi c Reports.

Abstract:

Triple-negative breast cancer (TNBC) is a distinct breast cancer subtype defi ned by the absence of estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2/neu), and the patients with TNBC are oft en diagnosed with higher rates of recurrence and metastasis. Because of the absence of ER, PR and HER2/neu expressions, TNBC patients are insensitive to HER2-directed and endocrine therapies available for breast cancer treatment. Here, we report that expression of atypical protein kinase C isoform, PKCλ/ι, signifi cantly increased and activated in all invasive breast cancer (invasive ductal carcinoma or IDC) subtypes including the TNBC subtype. Because of the lack of targeted therapies for TNBC, we choose to study PKCλ/ι signaling as a potential therapeutic target for TNBC. Our observations indicated that PKCλ/ι signaling is highly active during breast cancer invasive progression, and metastatic breast cancers, the advanced stages of breast cancer disease that developed more frequently in TNBC patients, are also characterized with high levels of PKCλ/ι expression and activation. Functional analysis in experimental mouse models revealed that depletion of PKCλ/ι signifi cantly reduces TNBC growth as well as lung metastatic colonization. Furthermore, we have identifi ed a PKCλ/ι-regulated gene signature consisting of 110 genes, which are signifi cantly associated with indolent to invasive progression of human breast cancer and poor prognosis. Mechanistically, cytokines such as TGFβ and IL1β could activate PKCλ/ι signaling in TNBC cells and depletion of PKCλ/ι impairs NF-κB p65 (RelA) nuclear localization. We observed that cytokine-PKCλ/ι-RelA signaling axis, at least in part, involved in modulating gene expression to regulate invasion of TNBC cells. Overall, our results indicate that induction and activation of PKCλ/ι promote TNBC growth, invasion and metastasis. Th us, targeting PKCλ/ι signaling could be a therapeutic option for breast cancer, including the TNBC subtype.

Wassil Nowicky

Ukrainian Anti-Cancer Institute, Austria

Title: Anti-Cancer preparation NSC 631570

Time : 13:50-14:10

Biography:

Wassil Nowicky, Ukrainian Anti-Cancer Institute, Austria

Abstract:

NSC 631570 consists of ions of greater celandine alkaloids. NSC 631570 is the fi rst and only cancer preparation with a selective eff ect, meaning that it is toxic against cancer cells but not against healthy cells. Th is has been confi rmed by 120 universities and research centers in the world. Th e next indications were provided by clinical use, where NSC631570 caused no noteworthy side-eff ects. It improved patients’ general condition as well as their immune status which had previously been impaired by chemotherapy. Th e next indication was provided by a study at the University of Miami, which calculated the therapeutic index of NSC631570 to be 1250. Th is is unusually high for an anti-cancer preparation. Th e therapeutic index of conventional cytostatic preparations is in the range of 1.4-1.8 meaning that an overdose can have fatal consequences. Th ere is no risk of an overdose with NSC631570 on account of its very high therapeutic index of 1250. Th e development of NSC631570 was a trail-blazing discovery. In the NCI test model, in contrast to conventional cytostatic preparations which caused growth inhibition only in some cancer cell lines - thiotepa inhibited the growth of MLI-09 (non-small lung cancer) and UOK-57LN (renal cancer) - NSC631570 killed all 60 tested cancer cell lines, which represent the eight important human tumours, including cell lines which were resistant to the strongest cytostatic drug at the time, cisplatin. Th is generated still more interest in scientifi c circles and leading scientists examined NSC631570. Many aspects of the eff ect of NSC631570 on cancer and normal cells have so far been studied. Nevertheless, the possibility exists that these eff ects are merely the results of an as yet unknown process which NSC631570 induces in cancer cells but not in normal cells. It can also be observed that in the urine of cancer patients who use NSC 631570 there occurs some specifi c odor and its color changes. Th is leads us to suggest that NSC 631570 enters into a biochemical reaction with some elements of cancer cells and if it were possible to isolate this product of the compound it could give us as a completely new method of early cancer diagnosis.

Hiroshi Kobayashi

Chiba University, Japan

Title: Target genes for acidosis-dependent anti-cancer drugsv

Time : 14:10-14:30

Biography:

Hiroshi Kobayashi has completed his PhD (1974) in biochemistry from University of Tokyo in Japan. After his postdoctoral training at Colorado University Medical Center in USA, he started to study adaptation strategies of microorganisms to acidic environments at Chiba University in 1978. His recent research is focused on mammalian cell functions under acidic conditions from 1996 at Graduate School of Pharmaceutical Sciences, Chiba University. He retired in March 2012 and continues his research as a Professor Emeritus at Chiba University. He has published more than 20 papers in reputed journals during the recent 10 years.

Abstract:

While mammalian blood and normal tissues are usually maintained at pH around 7.4, the extracellular pH drops below 6.5 in solid cancer nests. Enzymes which function preferentially at acidic pH may be the target molecules of anti-cancer drugs. Our group have found that the inhibition of protein prenylation attenuates proliferation of cancer cells at acidic pH, suggesting that an enzyme(s) to prenylate proteins is functioning under acidic conditions. In addition to the enzyme for protein prenylation, there may be other enzymes functioning under acidic conditions. To fi nd such enzymes, the expression of 24,000 genes was examined using a DNA array chip in mesothelioma cells, and the expression of approximately 700 genes was elevated at acidic pH. Th e elevated expression of these genes was found in other cancer cells grown under acidic conditions and in human specimens from cancer patients. Th ese results suggest that mammalian cells have many enzymes which function preferentially in acidic cancer nests, and that drugs inhibiting these enzymes could be potent candidates for anticancer chemotherapeutics with less side-eff ect, especially on immune systems in blood and normal tissues, because acidosisdependent drugs are expected to be less eff ective in tissues whose pH is alkaline. In fact, inhibitors of protein prenylation had little eff ect on proliferation and cytokine production of immune cells at alkaline pH. Th e screening under acidic conditions may be a useful way to fi nd new anti-cancer drugs which are eff ective in acidic cancer nests.

Biography:

Kang-Yell Choi is specialist in Cancer Research, Cell Biology, Biotechnology

Abstract:

Three decades aft er the identifi cation of Ras as an oncogene, the fi eld remains as dynamic and important as ever. Ras controls a wide variety of biological processes including cell growth, survival, and diff erentiation and is also involved in a number of diseases, including cancer and developmental disorders. However, despite the signifi cant progress that has been made, our understanding of Ras is still incomplete. As adding importance of K-Ras mutation in cancer biology we recently found that oncogenic K-Ras progress tumorigenesis and metastasis of colorectal cancer haboring APC mutations via activating cancer stem cells. Initial activation of β-catenin by APC loss and further enhancement through K-Ras mutation induces CD44, CD133 and CD166 expression (1). We also provide convincing evidence for a new Ras regulatory mechanism that provides a potential approach for the direct control of Ras instead of the well-known Ras regulation mechanisms of GDP/GTP exchange and the lipid-directed posttranslational modifi cation involved in membrane traffi cking. We not only present a detailed mechanism for Ras degradation involving its phosphorylation by negative Wnt/β-catenin signaling via GSK3β but also provide critical pathophysiological evidence related to human colorectal cancer (2). Th e in vivo role of the regulation of Ras stability and the involvement of Ras stabilization in colorectal tumorigenesis were further demonstrated using Adenomatous polyposis coli (Apc)-defective ApcMin/+ and Apc1638N mouse tumours and human colon cancers in various stages, as well as specimens of familial adenomatous polyposis (FAP) caused by Apc mutations. In this meeting, I will also discuss on our current status of the development of anticancer drugs controlling stability of β-catenin and Ras in control of colorectal cancer.

Biography:

Swei Sunny Hann has completed his MD from University of Guangzhou Traditional Chinese Medicine Guangzhou, Guangdong Province, China. She has published more than 8 papers in all SCI journals in English. Her work is currently funded by the Special Science and Technology Join fund from Guangdong Provincial Department of Science and Technology-Guangdong Academy of Traditional Chinese Medicine and the National Nature Scientific Foundation of China.

Abstract:

Baicalein, a natural fl avonoid obtained from the Scutellaria baicalensis root, has been reported to inhibit growth of human lung cancer. However, the detailed mechanism underlying this eff ect has not been well elucidated. We showed that baicalein signifi cantly inhibited the growth and induced apoptosis of NSCLC in a time- and dose-dependent manner. Baicalein induced RUNX3 and FOXO3a mRNA and protein expression, and increased phosphorylation of AMPK and ERK1/2. Moreover, the inhibitors of AMPK and ERK1/2 reversed the eff ect of baicalein on RUNX3 and FOXO3a protein expression. Interestingly, while compound C had little eff ect on blockade of baicalein-induced phosphorylation of ERK1/2, PD98059 signifi cantly abrogated the baicalein-induced phosphorylation of AMPK. Intriguingly, while silencing of RUNX3 abolished the eff ect of baicalein on expression of FOXO3a and apoptosis, silencing of FOXO3a signifi cantly attenuated baicalein-reduced cell proliferation. On the contrary, overexpression of FOXO3a restored the eff ect of baicalein on cell growth inhibition in cells silencing of endogenous FOXO3a gene and enhanced the eff ect of baicalein on RUNX3 protein expression. Finally, exogenous expression of RUNX3 increased FOXO3a protein and strengthened baicalein-induced phosphorylation of ERK1/2 and. Collectively, our results show that baicalein inhibits growth and induces apoptosis of NSCLC cells through AMPKα- and ERK1/2-mediated increase and interaction of FOXO3a and RUNX3. Th e crosstalk between AMPK and ERK1/2 signaling pathways, and the reciprocal interplay of FOXO3a and RUNX3 converge on the overall response of baicalein. Th is study reveals a novel mechanism for regulating FOXO3a and RUNX3 signaling axis in response to baicalein and suggests a new strategy for NSCLC associated targeted therapy.

Yong Xu

Nanjing First Hospital, Nanjing Medical University, China

Title: RelB-mediated EMT activation promotesbone metastasis of prostate cancer

Time : 15:10-15:30

Biography:

Shuang-yong Xu is a Senior Scientist in DNA Enzyme Division at New England Biolabs, USA. In 1978-1982 he studied B.S. in Microbiology, Nankai University, Tianjin, China. 1983-1989 he did Ph.D. in Microbiology, University of Iowa, Iowa City, IA. In 1989-1991 he did Postdoctoral Associate, New England Biolabs (NEB), Inc. Beverly, MA. 1996-2000 he got Certificate of Special Studies in Administration and Management from Harvard University. He is the inventor or co-inventor of over 42 patent awards in the United States.

Abstract:

The NF-KB signaling pathway is well-known to be critical for cancer development; our previous studies demonstrated that the RelB-based NF-KB alternative pathway is essential for tumorigenesis of prostate cancer. Here, we show that RelB contributes to bone metastasis of prostate cancer through an EMT-activating process. High constitutive nuclear levels of RelB were observed in human prostate cancer tissues with high Gleason scores. Up-regulation of RelB in prostate cancer cells led to cell invasion and migration, which was mediated by activation ofSnail I and Twist I. ChIP revealed that RelBbindsto NF-KB enhancer elements located at the 5’-fl anking regions of both Snail I and Twist I genes, which interact with Sp1-based promoters for transcriptional activation of the genes. In addition, the high levels of RelB also increased cell mineralization that was correlated to up-regulation of the bone formation relating protein, S100A4. Th e RelB-mediated aggressiveness of prostate cancer cells through Snail I- and Twist I-activated PI3K-AKT pathway, which was induced by TNFα, but suppressed by an anticancer agent, parthenolide. Th ese results suggest that the activation of NF-KB alternative pathway enhances metastasis of prostate cancer cells by activation of the EMT process.

Taha A. Kumosani

King Abdulaziz University, Saudi Arabia

Title: Hypermethylation of P15, P16, and E-cadherin genes in ovarian cancer

Time : 15:30-15:50

Biography:

Taha A Kumosani has studied Biochemistry and Biochemistry of Cancer for 25+ years, during which time he has authored more than 150 research articles. He has served on the editorial boards for many Scientifi c Journals. including his current membership with many Scientifi c Society.

Abstract:

Both p16 and p15 proteins are inhibitors of cyclin-dependent kinases that prevent the cell going through the G1/S phase transaction. E-cadherin is a transmembrane glycoprotein that mediates calcium-dependent interactions between adjacent epithelial cells. Two groups of patients were selected: the fi rst group suff ered from epithelial serous ovarian tumors and the second group suff ered from benign ovarian lesions; ovarian tissue samples from all the subjects (benign and malignant) were subjected to methylation-specifi c polymerase chain reaction for methylated and unmethylated alleles of the genes (E-cadherin, p15, and p16). Results obtained showed that aberrant methylation of p15 and p16 genes were detected in 64.29 and 50% of ovarian cancer patients, while E-cadherin hypermethylation was detected in 78.57% of ovarian cancer patients. Methy- lation of E-cadherin was signifi cantly correlated with diff erent stage of disease (p < 0.05). It was found that the risk of E-cadherin hypermethylation was 1.347-fold, while risk of p15 hypermethylation was 1.543-fold and p16 was 1.2-fold among patients with ovarian cancer than that among patients with benign ovarian lesions. In con- clusion, Dysfunction of the cell cycle and/or the cell–cell adhesion molecule plays a role in the pathogenesis of ovarian cancer and that the analysis of the methylation of p15 and E-cadherin genes can provide clinically important evidence on which to base the treatment.

Biography:

Larysa M.Skivka – ScD., PhD She has completed her PhD at the age of 28 years from R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine and postdoctoral studies from Taras Shevchenko National University of Kyiv. She presently is a head of the Department of Microbiology and General Immunology of SCE “Institute of Biology” of Taras Shevchenko National University of Kyiv. Area of scientifi c activity – immunomodulation as a component of adjuvant therapy under the tumor growth, functional polarization of phagocytes in the pathogenesis of infl ammatory diseases. She has published more than 13 papers in reputed journals and more than 40 abstracts in scientifi c congresses.

Abstract:

Introduction: Th e mixture of Alkaloids (NSC-631570) have been showed an anticancer activities against diff erent types of solid tumor. In particular this activities in combination with gemcitabine signifi cantly increased the median survival of advanced PDAC patients with respect to gemcitabine alone (10.4 vs 5.2 months; p<0.001). Furthermore, other studies showed an anticancer eff ect in prostate cancer patients also. Indeed, the cytotoxic eff ects of NSC-631570 was evident in preclinical studies in prostate cancer cell line (PC-3). In particular, using the auto-fl uorescence properties of this Drug (by UV light excitation) some author showed a diff erent up-take of drug in PDAC cells with respect to normal epithelial cells of pancreas (HNPE). Th e data of literature seem to indicate that this mixture of alkaloids had selective in cancer cell lines derived from diff erent tumor types, but not in normal cell lines. Aim: To investigate the concentration NSC 631570 in urine samples of prostate cancer patients using UV light approach to confi rm diff erent up-take of alkaloids mixture in both normal and prostate cancer patients. Materials & Methods: We studied opctical characteristics in urine samples (before and aft er the sublingual administration of the drug)using two diff erent absorption spectrums: UV light and fl uorescence at λ = 540 nm. We observed the variation of both intensity at 0,2,4 and 6 hours aft er administration. Urine samples from 2 prostate cancer patients (PC1 and PC2) and 3 healthy controls (HCs) were used. Results: Th e UV light absorption spectrum of urine HCsaft er NSC 631570 coincided almost completely with that of the drug. PC1 showed a similar absorption spectrum similar to NSC 631570 aft er 4 hours sublingual administration only. While, absorption spectrum ofPC2 was completely diff erent during the entire observation period compared with those observed in HCs (p<0.05). Urine fl uorescence PC1 increased in both PC1 and PC2 aft er the drug administration, till the end of the observation period nonlinearly. However, 6 hours aft er administration of the drug a moderate decrease of the fl uorescence intensity has been registered. Conclusion: Comparative analyses of urine optical characteristics of both healthy donors and prostate adenocarcinoma patients have been shown that absorption spectra under the UV light aft er sublingual administration of the drug NSC 631570,makes the diff erences betweenprostate adenocarcinoma and healthy patients. Probably, these data indirectly indicate diff erences concerning dynamics clearance of drug in diff erent subjects. Comparative study of urine fl uorescence intensity of healthy donors and patients with cancer pathology at λ = 540 before and aft er sublingual administration of the drug NSC 631570 in dynamics proved to be uninformative. In conclusion this method could be used to test whether non clinically pathologic subject might be aff ected by cancer.

Break: Coffee Break 16:10-16:25 @ Foyer

Ciobica Alin

Gr. T. Popa University of Medicine and Pharmacy, Iasi, Romania

Title: The relevance of the cytological diagnostic in the mamary gland cancer

Time : 16:25-16:45

Biography:

Dr. Alin Ciobica is currently affiliated to Department of Biology, "Alexandru Ioan Cuza" University, Center of Biomedical Research of the Romanian Academy, Romania, continuing research in the specialized scientific area of biology. Dr. Alin Ciobica is serving as an honorary reviewer for journal of blood disorders and transfusion & other reputed journals and has authored several articles along with chapters in different books related to biology.

Abstract:

Breast cancer is the second leading cause of cancer death in women, while in Estearn Europe is the most common form of diagnosed cancer. Out of the multiple possibilities of early detection of mammary neoplasia that have been elaborated, only mammography has proved to be a simple, effi cient method and of a high sensitivity, which can reach out to 90%. However, the cytological confi rmation of diagnosis allows us to perform the preoperative radiotherapy treatment or polychemioterapy; which is why we analyzed the informative value of these diagnosis methods in stage I mamary gland cancer (MGC). In this way, in the present report we demonstrated that collecting samples through fi ne-needle aspiration biopsy allows the cytological confi rmation of the diagnosis of stage I MGC in 30.7% cases. Moreover, in stage I MGC young patients under 35 years, the cytological confi rmation rate was 22.2% and was signifi cantly decreased, as compared to the cytological confi rmation rate in patients older than 35 years (37.9 %). Also, for a tumor diameter < 0.5 cm, the prevalence of cytological confi rmation was only 10.3%, while for the diameter of 0.6 – 1.0 cm the cytological confi rmation was around 40.0%. Th erefore, in order to improve the cytological diagnosis, the confi rmation rate for the tumor biopsy through the USG of the mammary glands is required. Moreover, the cytological investigation of the smear obtained by the fi rst and second puncture was instrumental in confi rming the diagnosis in 41.3% and respectively 17.4% cases. Also, the subsequent repetition of the punctures was not useful, as it helped to confi rmation of the diagnosis only in 9.3% cases. In addition, the frequency of diagnosis cytological confi rmation was depending on the tumor histopathological form and type of growth. Th us, the lowest prevalence was in the mixed forms - 12.5% cases, lobular cancer - 24.4% cases, while regarding the type of growth, for the rare forms the cytological confi rmation rate was 7.7% and 31.5% for the schiros growth type.

Surekha M V

Pathology Division, National Institute of Nutrition, India

Title: Effect of dietary fatty acids on development of carcinogen-induced breast cancer in female fisher (F344) rats

Time : 16:45-17:05

Biography:

Background and objectives: Objective of our study was to assess eff ect of dietary fatty acids (saturated vs unsaturated fatty acids vs transfats) in development of Dimethylbenzanthracene(DMBA) induced experimental mammary tumours in female fi sher rats. Methodology: Eighty weanling female fi sher (F344) rats were divided into fi ve groups of 16 each and fed with synthetic diets containing partially-hydrogenated vegetable oil / PHVO (transfat), palmolein (saturated fatty acids) , sunfl ower oil (n-6 PUFA), soyabean oil (α-linoleic acid) and sunfl ower + fi sh oil(LC n-3 PUFA) for 4 months aft er which 8 rats from each group were administered DMBA orally, once a week, for 4 weeks and continued on same diet for 8 months, while remaining 8 rats of each group were continued on respective diets. Results: Total serum SFA level was not aff ected by type of dietary fat, total MUFA level was highest in PHVO group, LC n-6 PUFA levels were not signifi cantly diff erent among groups and total LC n-3 PUFA levels were highest in sunfl ower oil + fi sh oil group. Number of tumours were least in PHVO and highest in n-6 PUFA group. Adenocarcinoma was observed as predominant tumour type and metastatic tumours, least common type, noted only in SFA diet group. Estrogen receptor positivity was mostly seen in n-3 PUFA group, progesterone receptor positivity in sunfl ower oil + fi sh oil group while PHVO group showed highest aromatase positivity. Conclusion: Dietary fatty acid composition to some extent refl ected in plasma phospholipid fatty acid composition. Transfats caused development of mammary tumours. N-3 PUFAs were associated with low and n-6 PUFAs with high tumour development.

Abstract:

Background and objectives: Objective of our study was to assess eff ect of dietary fatty acids (saturated vs unsaturated fatty acids vs transfats) in development of Dimethylbenzanthracene(DMBA) induced experimental mammary tumours in female fi sher rats. Methodology: Eighty weanling female fi sher (F344) rats were divided into fi ve groups of 16 each and fed with synthetic diets containing partially-hydrogenated vegetable oil / PHVO (transfat), palmolein (saturated fatty acids) , sunfl ower oil (n-6 PUFA), soyabean oil (α-linoleic acid) and sunfl ower + fi sh oil(LC n-3 PUFA) for 4 months aft er which 8 rats from each group were administered DMBA orally, once a week, for 4 weeks and continued on same diet for 8 months, while remaining 8 rats of each group were continued on respective diets. Results: Total serum SFA level was not aff ected by type of dietary fat, total MUFA level was highest in PHVO group, LC n-6 PUFA levels were not signifi cantly diff erent among groups and total LC n-3 PUFA levels were highest in sunfl ower oil + fi sh oil group. Number of tumours were least in PHVO and highest in n-6 PUFA group. Adenocarcinoma was observed as predominant tumour type and metastatic tumours, least common type, noted only in SFA diet group. Estrogen receptor positivity was mostly seen in n-3 PUFA group, progesterone receptor positivity in sunfl ower oil + fi sh oil group while PHVO group showed highest aromatase positivity. Conclusion: Dietary fatty acid composition to some extent refl ected in plasma phospholipid fatty acid composition. Transfats caused development of mammary tumours. N-3 PUFAs were associated with low and n-6 PUFAs with high tumour development.

M. SatyaVani

National Institute of Nutrition, India

Title: Sprague Dawley/NIN hairless mutant rat–A model to study carcinogenesis?

Time : 17:05-17:25

Biography:

M Satya Vani has completed her PhD. from Osmania University. She is working as a Technical Offi cer at NCLAS, NIN, Hyderabad, India and has 27 years’ experience in breeding management of laboratory animals. She also Underwent GLP training in IIBAT (International Institute of Biotechnology and Toxicology), Chennai, Tamilnadu, India. Dr. M. Satyavani has major involvement in establishing WNIN Obese rat model. She has published 8 papers to her credit in peer reviewed International Journals. She also attended several National and International conferences. Currently, she is the Principal Investigator for two intramural projects and Co-investigator in two more projects. She is further serving as a Treasurer of Indian Women Scientists Association (IWSA).

Abstract:

Spontaneous mutations in rodents are valuable experimental models to study human disorders in biomedical research. Nude mutant rats are widely used in immunology, percutaneous drug absorption, wound healing, skin pharmacology and experimental carcinogenesis. Hypotrichosis (hairless) mutation was observed for the fi rst time in SD rat colony at National Centre for Laboratory Animal Sciences, NIN, India. Th e parents identifi ed were isolated and further propagation was carried out by selective breeding. Th e data on morphological features in each generation have been recorded. At present, the mutant is in 9th generation. Studies have been conducted to evaluate the new SD/NIN hairless mutant rat for biochemical, immunological and molecular characterization as well as histopathhological evaluation. Ninety days old (12 males and 12 females) animals both homozygous and heterozygous taken were housed using standard experimental conditions and observed for changes in ageing. Four females and two males developed spontaneous tumors. However, the dimensions as well as the weight were recorded and evaluated for histopathological analysis. Th e results of the histopathological evaluation showed that most of the tumors were fi bro -adenomas with predominant fi brous tissue which may progress to malignancy, if left untreated. Th e incidence of tumors was more in females than in males. As these mutant rats are hairless, depilation (time consuming) is not required and therefore, the tumors can easily be identifi ed. Based on the above features it is presumed that mutant model may be used to study carcinogenesis and tumor therapy in future.

Nirmala Kota

National Institute of Nutrition, India

Title: Chemopreventive effects of ginger

Time : 17:25-17:45

Biography:

Nirmala Kota, PhD in Nutrition from Osmania University, Hyderabad, India with over thirty years experience in research and academics. Currently working as a Scientist in National Institute of Nutrition on projects related to Genotoxicity, Nutrition and Cancer.

Abstract:

Ginger is considered to be one of the most important nutraceutical plant and it contains bioactive substances like gingerols shogaols and paradols that exhibit antioxidant, antimutagenic, antigenotoxic and anticarcinogenic properties. Th is article provides an insight on the studies regarding cancer preventive potential of ginger. An invivo experiment was conducted to study the eff ect of ginger feeding on drug metabolizing enzymes in rats. Stimulatory eff ect due to ginger feeding was observed in tissues on GST, QR activity and antioxidant enzymes. Inhibition in the formation of malondialdehydes and reduction in the protein oxidative products in liver and kidney further supported its antioxidative potential. In continuation, a study was undertaken to see the eff ect of ginger under induced oxidative stress in streptozotocin induced diabetic rats. Dose-response increase in the activity of SOD, Catalase and GSHPx was observed. Dose-related eff ect was seen in the inhibition of MDA levels in liver in both non-diabetic and diabetic groups compared to control group. Reduction in the carbonyl levels was also observed in both the groups compared to control and a dose-response relation was seen. Th e DNA damage in blood of diabetic rats fed with ginger decreased showing a dose-dependent inhibitory action on DNA damage. Cytogenetic damage is considered to be one of the biomarker of genotoxicity. Peripheral blood lymphocytes were obtained from smokers, non-smokers and females. Trans stilbene oxide (TSO) was used to induce genetic damage in blood lymphocytes. Micronucleus expression was investigated in cytokinesis-blocked human lymphocytes following invitro exposure to TSO which induced signifi cant number of micronuclei. Treatment of cultured cells with ginger extract signifi cantly inhibited the formation of micronuclei. Genotoxicants induce mutations resulting in DNA damage .In a similar study using comet assay as a tool the antigenotoxic potential of ginger. B(a)P an ubiquitously present carcinogen was used to induce DNA damage that was quantitated in terms of comet ratios. A signifi cant reduction in comet ratios was seen in the cells treated with carcinogen along with ginger extract. Enhancing the sustainable use and conservation of indigenous knowledge of useful and medicinal plants like ginger may benefi t and improve the living standard of particularly the rural population.

Hemalatha Sanagaram

National Institute of Nutrition, India

Title: Sesame lignans: Potent components as nutraceuticals/functional foods

Time : 17:45-18:05

Biography:

Hemalatha Sanagaram was awarded her PhD in the year 2002 from Osmania University, Hyderabad. She has been working in the area of lipid chemistry with specifi c emphasis on the role of minor components present in the non glyceride fraction of oils in health and disease. She has published papers in peer reviewed International journals.

Abstract:

Oxidative stress is a key component in several chronic degenerative disease including cancer. Sesame has long been known to have both nutritional and medicinal value. However, the scientifi c basis of the health claims of sesame is not clear yet. Th e fatty acid composition and the tocopherol levels do not completely explain the high stability of sesame oil and these unusual characteristics are attributed to its non-glyceride components, i.e. the lignans, namely sesamin and sesamolin. Sesamin has been shown to have hypocholesterolemic and immunomodulatory properties while sesamolin is the precursor ofsesamol and sesaminol. Studies at NIN were focused to evaluate the potency of sesame lignans in biological (invitro and invivo) systems and foods. Sesamin and sesamolin were isolated and crystallized from highlignan cultivars, and their purity was confi rmed by spectral analysis.Although lignansper se were weak antioxidants they enhanced the antioxidant activity of vitamin E, sugesting that sesame lignans may have sparing eff ects on tocopherols. Th e eff ects of feeding sesamin and sesamolin on Fe2+-induced oxidative stress in rats showedincreased bioavailability of tocopherols, probably due to regeneration of oxidized tocopherols. Addition of sesame lignans to edible oils resulted in increased thermal stability suggesting that sesame lignans may have potential application as natural antioxidants in the edible oil and food industry; Th e synergistic eff ects of lignans with tocols has nutritional and therapeutic implications. Th erefore sesame lignans may be considered as active ingredients of nutraceuticals/ functional foods.

Biography:

Joan Fabian Fernandez de la Vega, General Calixto Garcia´s Teaching Hospital, Cuba

Abstract:

Introduction: Lung cancer is one of the major causes of global mortality. A delay in diagnosis is a signifi cant contributory factor aff ecting survival rates and prognosis. Objective: To identify the clinical characteristics of patients with a histological diagnosis of lung cancer at Joaquin Albarran´s Teaching Hospital, Havana, Cuba, between 2007 and 2010 and to assess the diff erent delays in diagnosis times. Methods: A retrospective descriptive study of patients diagnosed with lung cancer was undertaken to determine the delays in diagnosis corresponding to the patient and the National Health System (inclusive of primary care and the secondary health system). Results: Of the 54 patients included in the study, 74.1% were male, predominantly in the age group of 51-60 years old. Th e fi rst symptoms experienced by patients were identifi ed as cough, dyspnea and weight loss in 43, 29 and 21 patients respectively. 61.1 5 of all patients had fi rst presented at the primary care level. Th e mean delays in diagnosis at the levels of primary and secondary care were identifi ed as 16.2 and 29.1 days respectively. It was observed that the mean patient-dependent delay was 36.05 days, and found to constitute the majority of the total diagnostic delay time. Th e symptoms that were found to motivate patients to seek medical care within seven days were cough and dyspnea. Conclusions: Th e delay in diagnosis of lung cancer is considerably infl uenced by patient-dependent factors. Cough and dyspnea are the main reasons patients will seek medical care.

Biography:

Professor Weidong Han, M.D. PhD, is the director of Department of Molecular Immunology/Bio-therapeutic, director of Department of Stem Cell and Tissue Regeneration in Chinese PLA General Hospital. He is a pioneer in the fi eld of tumor immunotherapy, initially developed the clinical translation of chimeric antigen receptor T (CART) cells in China. He holds 10 projects of clinical trial, including 8 registered CART-based trials (CART19, CART20, CART30, CART33, CARTEGFR, CART-HER-2, and CART-138). The corresponding patents were also applied or obtained in China. In recent 10 years, he obtained 9 grants in China and published more than 80 papers on International journals.

Abstract:

In this phase I/II clinical study (NCT01869166), we have evaluated for the fi rst time the safety and effi cacy of EGFR-targeted chimeric antigen receptor-modifi ed T (CAR-T) cells in patients with epidermal growth factor receptor (EGFR) positive (>50% expression), unresectable, and/or relapsed/refractory solid tumors. 24 eligible patients received escalating doses of EGFR-targeted CART cells infusions. Th e EGFR-targeted CART cells were generated from peripheral blood aft er a 10 to 13-day in vitro expansion. Serum cytokines and copy numbers of CAR-EGFR transgene in peripheral blood and in tissue biopsy were monitored periodically. Th e clinical responses were evaluated with RECIST1.1 and immune-related response criteria, and adverse events were graded with CTCAE 4.0. Th e EGFR-targeted CART cells infusions were well-tolerated. Only 3 out of 24 patients exhibited Grade 2 cytokine release syndrome within one week post infusions. Nineteen of 24 evaluable patients (17 lung cancers, 5 cholangiocarcinomas, 1 pancreatic adenocarcinoma, and 1 renal cell carcinoma) had clinical response (DCR=79%), including 2 ongoing CR achieved by patients with cholangiocarcinoma, 4 PR (1 cholangiocarcinoma, 1 pancreatic carcinoma, and 2 lung cancers), and 13SD. Th e median dose of transfused CAR+ T cells was 1.18×107 cells/kg (IQR, 0.76 to 1.43×107 cells/kg). Pathological eradication of EGFR positive tumor cells aft er EGFR-targeted CART cells treatment can be observed in tumor biopsies, along with clear evidence of the CAR-EGFR signal detected in tumor-infi ltrating T cells in all 5 biopsied patients. Th e EGFR-targeted CAR T cells therapy for EGFR-positive, advanced or relapsed/refractory solid tumor patients is safe and eff ective.

Biography:

Devathri Nanayakkara is a fi nal year PhD student from Eskitis Institute for Drug Discovery, Griffi th University. She is working on the deubiquitylating enzyme, USP9X under the supervision of Dr Stephen Wood.

Abstract:

Oral squamous cell carcinoma (OSCC) represents one of the most common cancers in the world. Identifi cation of oncogenes, onco-suppressors and their molecular mechanisms is necessary to understand the process of oral tumorigenesis. Recently, deubiquitylase enzyme, USP9X, has been implicated as a tumor suppressor in oral carcinomas. Th is study aimed to further investigate USP9X’s role by knocking it down in four OSCC cell lines: SCC15, CAL27, FaDu and Detroit 562. Over 6 days all four cell lines displayed a reduction in cell numbers in the absence of USP9X and two of the cell lines, CAL27 and FaDu, revealed cell cycle alterations. USP9X regulates the mTOR pathway which plays a critical role in cell cycle progression. CAL27 and FaDu showed signifi cant down regulation of the mTORC1 target, pS6 protein, in the absence of USP9X, probably causing the delay in cell cycle progression and decrease in cell numbers. In the other two cell lines, SCC15 and Detroit 562, diff erences in cell numbers were evident only aft er four days in culture. To determine if the delayed eff ect is due to terminal diff erentiation, levels of involucrin were assessed but no diff erence was observed. Interestingly, levels of MCL1, a pro survival protein and a USP9X substrate decreased in these cells aft er the fourth day. Hence the reduced cell numbers could be due to increased cell death. Th is study reveals that the absence of USP9X aff ects the proliferation/viability of OSCC cell lines. As previously shown, the roles of USP9X can be highly context specifi c and vary in early and advanced forms of oral cancers.