Pati Debananda
Baylor College of Medicine, USA
Targeting Ewing Sarcoma Tumors with Cohesin Mutations
Biography:
Professor Pati is a highly accomplished cancer biologist who is an internationally recognized leader in the field of chromosomal cohesion and Separation and its role in carcinogenesis. He has a highly impressive track record not only in basic biology of chromosomal cohesion and separation, but devising novel and innovative approaches to target the cohesin pathway for treating refractory human cancers. He is widely recognized nationally and internationally as a creative and innovative scientist and is specifically recognized for his identification and targeting of the cohesin-protease, Separase for cancer therapy. Separase, an enzyme important for resolving chromosomal cohesion, is a novel oncogene and promoter of aneuploidy and tumorigenesis that Professor Pati demonstrated is an ideal target for cancer therapy. His laboratory was first to show that Separase is an oncogene and aneuploidy promoter. In a series of publications in high impact journals, Professor Pati and his colleagues demonstrated that overexpression of Separase in mouse models not only induces aneuploidy but also results in tumorigenesis.
Abstract:
Ewing sarcoma (EWS) is an aggressive and highly metastatic pediatric cancer with a dismal prognosis. We present here a series of preclinical studies to develop a set of ‘first-in-class’ compounds that exploit a synthetic lethal interaction between chromosomal cohesin subunit SA1 and its functional paralog SA2 to treat relapsed EWS tumors that often present with SA2 mutations. Recent genomics studies have reported pathogenic mutations in the SA2 coding sequence in >21% of relapsed EWS tumors. Whereas SA2 is frequently mutated in human tumors, only rarely are mutations reported in the SA1 gene. siRNA knockdown of SA1 or SA2 has no significant effect on cell lethality, but knockdown of both SA1 and SA2 in the cells leads to cell death, indicating a synthetic lethal interaction. Additionally, studies in our laboratory and others show that knockdown of SA1 in SA2-mutant tumor cells but not in SA2-WT cells leads to significant cell death, suggesting that SA subunits can be targeted.
We posit that inhibition of SA1 function in SA2 mutant tumors represents an effective and novel way to selectively inhibit proliferation of EWS and other human cancers with high levels of SA2 mutations. Using a high throughput screen, we have identified a small molecule, which we named stagX1, that selectively reduces SA1 protein levels and kills EWS cells bearing SA2 mutations but has no effect on cells with wild-type (WT) SA2. Furthermore, our studies demonstrate that stagX1 significantly inhibits primary tumor growth in an EWS mouse xenograft model. In toxicology studies, we found that stagX1 causes no observable acute or chronic toxicity in vivo. However, stagX1 possesses an unfavorable plasma stability, necessitating the search for improved derivatives. We hypothesize that developing stagX small molecular inhibitors of SA1 will lead to an entirely new class of drugs to target SA2 mutant, refractory EWS and other human tumors, and open a new path to improve treatments for EWS and other cancers with high levels of SA2 mutations.
We continue our medicinal chemistry efforts to identify additional members of the stagX class of SA1-small molecule inhibitors with improved in vitro and in vivo drug-like properties, and to test their ability to effectively target primary tumor growth and tumor metastasis. To understand the pathophysiology of SA2 mutations, we are examining the biology of SA2 mutations in the development of EWS using a conditional knockout SA2 mouse model. Targeting tumor suppressor genes often mutated in tumors through synthetic lethality is a new paradigm for cancer treatment. Clinically relevant synthetic lethal agents such as stagX1 that kill SA2-mutant cells by synthetic lethality while sparing the normal cells is targeted and advantageous over the current “kill them all” forms of chemotherapy. Therefore, our effort to develop a precision drug against SA2 mutations, a novel and untested therapeutic target, to treat EWS is timely and innovative, and will significantly impact the treatment of relapsed EWS tumors.
Ashok Srivastava
ClinFomatrix, and Cure Pharmaceuticals Inc, USA
Challenges in Breast Cancer Treatment and Drug Safety
Biography:
Dr. Ashok Srivastava is Chief Executive Officer and Chief Medical Officer of ClinFomatrix Oncology and Chief Executive Officer of Cure Pharmaceuticals, Inc., USA.. He was also founder and Chief Medical Officer of CareBeyond - A Radiation Cancer Center in USA. He has more than 17 years of experience in drug development , medical affairs and commercialization of cancer drugs including radiopharmaceutical and supportive care; Phase I – 4, and marketing commercialization of immuno-oncology, hematology, oncology and radio pharmacetuical drugs in USA , EU and Japan. He is leader in Cancer Drug Development Worldwide large Phase 2 and 3 clinical trials in many countries. He contributed to 21-INDs and 7-NDAs of Cancer Drugs and supportive care, acquisition /merger of pharma and drug for more than $300 million . He received his clinical, medical training & worked at renowned medical centers and pharmaceutical institutions worldwide; Walter Reed Army Institute of Research and Medical Center, Daiichi, Sumitomo, Pharmacia, Pfizer, Sopherion Oncology., Eisai Oncology, and Spectrum Pharmaceuticals. He received his Clinical, Medical & Business educations from All India Institute of Medical Sciences, New Delhi, India ; Academy of Medical Sciences, Czechoslovakia; School of Medicine Nagasaki University, Nagasaki, Japan, and Pharmaceutical Business at Rutgers University Business Management, New Jersey, USA. He played key role in dramatic expansion of oncology drug – developed cancer drugs- Sutent (Sunitinib), Evoxac (Cevimeline HCl), and liposomal doxorubicin (Myocet) in combination with Herceptin & Paclitaxel for HER2 positive metastatic breast cancer patients and latuda (Lurasidone) for schizophrenia . He is one of the inventors of Japanese encephalitis vaccine (IXIARO) . He has published more than 85 papers in National and International Journals, more than 120 abstracts, 3 book chapters and 2 patents. He is recipient of numerous National & International prestigious medical awards and recognitions from United Nations, Ministry of Health, Japan, and Department of Army, Walter Reed Army Medical Center and Walter Reed Army Institute of Research, Washington DC, USA. He served as medical advisor to Poniard Pharmaceutical for small cell lung cancer in USA, EU and India. He is member of numerous prestigious organizations; America’s Top Oncologist of the years 2007- 2011, Breast Cancer Foundation , Indian Society of Oncology, American Society of Clinical Oncology, American Society for Therapeutic Radiology & Oncology, American Association of Cancer Research, and International Society of Lung Cancer. Dr. Srivastava is a strategic medical advisor and Board Member to several pharma in USA for clinical, regulatory and supervises cancer drug development . Recently Dr. Srivastava was awarded membership of Japan External Trade Organization, USA. Dr. Srivastava is a Leader in Drug Safety, pharmacovigilance of hematology, Oncology drugs and built a global drug safety and pharmacovigilance companies in USA, and India. Dr. Srivastava was invited as an honorable speaker at drug safety & Pharmacovigilance congress in London, UK , China and India in Jan 2012, 2013 and 2017. Dr. Srivastava brought 2 cancer drugs & a vaccine in global market for approx 3 – 3.5 billion $ global sales. He serves as board of director s for oncology virtual pharma companies in USA .
Abstract:
Breast cancer is the most common cancer in women worldwide. It is also the principle cause of death from cancer among women globally. Despite the high incidence rates, in Western countries, 89% of women diagnosed with breast cancer are still alive 5 years after their diagnosis, which is due to detection and treatment. Breast cancer incidence has been increasing. In 2015, an estimated 231,840 new cases of invasive breast cancer are expected to be diagnosed in women, along with 60,290 new cases of non-invasive (in situ) breast cancer. About 2,350 new cases of invasive breast cancer are expected to be diagnosed in men in 2015. A man’s lifetime risk of breast cancer is about 1 in 1,000.Breast cancer incidence rates in the U.S. began decreasing. One theory is that this decrease was partially due to the reduced use of hormone replacement therapy (HRT) after the results of a large study called the Women’s Health Initiative were published in 2002. These results suggested a connection between HRT and increased breast cancer risk.About 5-10% of breast cancers can be linked to gene mutations. Mutations of the BRCA1 and BRCA2 genes are the most common. On average, women with a BRCA1 mutation have a 55-65% lifetime risk of developing breast cancer. For women with a BRCA2 mutation, the risk is 45%. Breast cancer that is positive for the BRCA1 or BRCA2 mutations tends to develop more often in younger women. An increased ovarian cancer risk is also associated with these genetic mutations. In men, BRCA2 mutations are associated with a lifetime breast cancer risk of about 6.8%; BRCA1 mutations are a less frequent cause of breast cancer in men.
All drugs for breast cancer treatment developed and in market cause mild to several side effects, and the safety, pharmacovigilance, signal detection a and risk management of breast cancer drugs are difficult to manage. A series of challenges of breast cancer therapy and the drug safety will be discussed at the meeting.
Graeme Williams
Harvard Clinical Research Scholar, UK
The role of stress, diet and chemical exposures upon aromatase up-regulation and breast cancer risk
Biography:
Physician, Scientist, Molecular Endocrinologist, (Molecular and CellularMedicine Group, University of Reading, UK) and Harvard Clinical ResearchScholar, (Royal College of Physicians (Lond)/UCL)Current Research: The role of aromatase, GPER, cortisol, poor carbohydratedietary choices and chemical exposures, upon the pathogenesis of obesity,NAFLD, insulin resistance, type two diabetes, breast and prostate cancer, andsexual dysfunction in men and women.In other words:- how stress, injudicious diets and everyday chemicalexposures, cause obesity, metabolic syndrome, type 2 diabetes and hormonerelatedcancer.
Abstract:
This presentation will focus upon the everyday factors that up-regulate aromatase, and theirassociation with known breast cancer risk factors.The up-regulation of aromatase produces increased intracellular estradiol, increases ER-αactivation, increases GPER activation, and in combination with insulin receptor dysfunction,causes aberrant downstream signaling, to induce cell proliferation and promote malignanttransformation in ER-α breast, endometrial and prostate cells.As such, anything that increases aromatase activity, will increase intra-cellular estradiolbiosynthesis and cell proliferation.Increased breast density, raised unopposed estradiol levels, oral contraceptive use, familyhistory, nulliparity and early menarche, alcohol consumption, obesity and type-two diabetes,are all human breast cancer risk factors. Excess stress, inappropriate dietary habits andendocrine disrupting chemical exposures, have also been implicated with ER-α positivecancers of the breast, endometrium and prostate.Mammographic breast density, an estradiol-related breast cancer risk factor, confers a 6-foldincreased risk, adjusted for all other factors, and pre-existing atypical hyperplasia and lobularhyperplasia increase the risk of breast cancer 5-fold.Although elevated serum levels of estradiol have long been classed as a breast cancer riskfactor, normal breast tissue estradiol concentrations and intra-tumoral breast cancerestradiol concentrations, can be 10-20 higher than serum levels, irrespective of pre- or postmenopausalstatus ….indicating that significant estradiol biosynthesis occurs within the breasttumor microenvironment, consistent with increased aromatase activity, and proportional tohistological grade and progression.Oral contraceptive use with combined ethinylestradiol and progestins have been reported toincrease the risk of breast cancer 3.2 fold, depending on the incorporated progestin.Epidemiological studies reveal that every 10 grams of alcohol consumed, confers a 10%increase in relative breast cancer risk, irrespective of menopausal status or the type ofbeverageObesity, increased BMI, raised waist to hip ratio, increased percentage fat, type two diabetes,insulin resistance and metabolic syndrome, are all modifiable breast cancer risk factors, andare all directly associated with aromatase up-regulation and increased intracellular estradiolbiosynthesis.Hyperinsulinemia associated with inappropriate eating, metabolic syndrome and type twodiabetes, also up-regulates aromatase production and estradiol synthesis; hence the closeassociation between obesity and diabetes, and the increased incidence of breast cancer,endometrial cancer, ovarian cancer, prostate cancer; and even the increased incidence ofbenign growth disorders of estrogen-sensitive tissues such as atypical ductal hyperplasia,gynecomastia, menorrhagia, endometriosis, anovulatory cycling, prostatic hypertrophy andobesity itself.Similarly, the psychological stress of worry and concern, the physical stress of inflammationand injury, and exposure to endocrine disrupting compounds, have been found to have apositive association with breast cancer.This presentation will also briefly consider a study, where human breast cancer cells wereexposed to twenty-eight endocrine-active, environmental chemicals and endogenouscompounds, (estradiol, estrone, ethinylestradiol, testosterone, insulin, DDT, methoxychlor,BPA, BPS, cortisol, phenols and plastic derivatives) at concentrations detected in humantissues, to determine their effects upon aromatase expression, aromatase activity,intracellular estradiol biosynthesis, and cell proliferation in relation to human breast cancer.In essence, stress, poor dietary habits and the inadvertent exposure to everyday chemicals,as confirmed in this study, contribute to increased intracellular estrogen biosynthesis innormal and diseased estrogen-sensitive tissues.By understanding the association between exposures and increased estradiol biosynthesis inthe tumor microenvironment, in relation to breast cancer risk factors, we can hopefullyreshape health initiatives, reduce suffering, and reduce the incidence of ER-positive cancers.
Henrik Bohr
The Technical University of Denmark, Denmark
New perspectives in Anti-sense research (computation/clinical) for application to Cancer Treatment.
Biography:
Henrik Georg Bohr, born September 25, 1951 in Copenhagen, Denmark to Dr.
and Mrs. Hans H. Bohr and Ann Skov.
• Danish nationality, married (with Yayoi Bohr), two children (Adam and Yuki).
• Currently working at Chemistry Dept. The Technical University of Denmark, Kgs. Lyngby, Denmark.
• Currently living in Pipersvej 13, 3520 Farum. Denmark.
Education
Cand. Scient. Degree from Niels Bohr Institute, Copenhagen University, 1979.
Doctor Technical at DTU, Thesis accepted April 1998 (Defence Sep. 4. 1998).
Appointments
Visiting Professor at University of Illinois at Urbana-Champaign (UIUC) in the Department of Physical Chemistry, Noyes Lab., Urbana, Illinois, USA, 1990-1992.
Visiting Professor at Heidelberg University and at German Cancer inst., Germany, 1993-1994.
Associate Professor at the Technical University of Denmark, CBS, Center of Biological Sequences Analysis, Department of Physical Chemistry, Kgs. Lyngby, Denmark, 1994-1997.
Tenured Associate Professor in the Department of Physics, DTU, Kgs. Lyngby, 1997 - 2003.
Director of QuP-Centre (EU centre of excellence), Department of Physics, The Technical University of Denmark, Kgs. Lyngby, November 2001 - present.
Full/Assoc. Professor in the Department of Physics, The Technical University of Denmark, 2003 – 2015 and Visiting Professor in Department of Chemistry, The Technical University of Denmark, 2015-2018.
Published over 200 scientific articles including around 50 communica-tions to scientific meetings in international journals in the area of theoretical physics, biophysics and biotechnology, 5 science books in biophysics and 7 patents.
Member of the Royal Danish Academy of Science and Letters, Danish Academy of Natural Science(DNA) and the Portuguese Science Academy.
Abstract:
A combined effort has been performed computationally as well as clinical on different important oligonucleotides with modifications used in anti-sense research. The anti-sense research in this context is about silencing certain genes and proteins in cancer diseases. The oligonucleotides are modified as phosphorothioates (with LNA (locked Nucleic Acid) changes which are crucial for cellular uptake and for binding to targeted strands. The theoretical and experimental techniques employed are molecular computation using Quantum Mechanics, QM, for producing electronic structures for the target molecules and chromatography experiments to distinguish and characterize the various molecules under investigation. The huge computer calculations on these large molecules, containing more than 600 atoms, are performed with ab initio quantum methods that are giving detailed electronic information on energy and bonding, and can differentiate between diastereoisomers i.e. chiral states. Furthermore differential geometry techniques are used to develop and analyze electrostatic isopotential surfaces that in principles can tell how drug molecules interact with others (Bohr 2017).
Physical and chemical descriptors of the oligonucleotides are derived from the atomic calculations and used for characterizing the theoretical and experimental data for the chiral state of the oligonucleotides.
Selecting the right chiral state of a drug is crucial for its effect and for avoiding side-effects. Experiments have shown that a particular one out of 2 chiral states could be an effective drug based on its surface form. However, it can be demonstrated that even a small change, e.g. interchanging the positions of 2 atoms, can have a huge effect on the overall structure of the molecule but on the other hand also used to design new drug molecules. Anti-sense compounds are expected to play an important role in cancer therapy (Stein 1989, Watts 2012).
Won-Chul Lee
The Catholic University of Korea, South Korea
Current Status of Cancer Screening in Korea
Biography:
Won-Chul Lee did his BM, Ms and Doctor of medicine from Catholic university of Korea. He is currently working as an advicer committee, Quality control of national cancer screening program at National Cancer Center of Korea. Previously, he worked as a Dean of Graduate School of Public Health at The Catholic University of Korea. He was also a Chairman, Board of Directors at The Korean Society for Preventive Medicine and also played the role of a Representative of Korea, ICSN (International Cancer Screening Network)
Abstract:
Cancer is the leading cause of death in Korea. So Cancer control is one of the most important issues.10-year plan for cancer control was started in 1996 in Korea. Now the Third Term Comprehensive Plan for Cancer Control (2016-2020) at the national level is being implemented.Cancer screening is actively being performed for cancer control.In Korea, Cancer screening is provided by two tracks. One is National Cancer Screening Program and the other is screening from private sector.National cancer screening program was started in 1999. The Program provides targeted population for five cancers- stomach, liver, colorectal, breast and cervix.Stomach cancer screening is provided for over 40 yrs old, every 2 yrs using endoscopy or UGIS. For Breast, over 40 yrs old, every 2 yrs using Mammography. For Cervix, over 20 yrs old, every 2 yrs using Pap Smear. For colorectal cancer screening, over 50 yrs old, every 1 yr using immunochemical FOBT. Liver Cancer screening is provided only for high risk group using Sonography and AFP every 6 months for over 40 yrs old.The clinical guideline for cancer screeningwas revised using GRADE by National Cancer Center in 2015.For the subjects below 50% of income, the cost for screening is free. And For the subjects over 50% of income, the cost is subsidized by 90% from the National Health Insurance, so subjects only pay for 10% of the cost.The average lifetime screening rate of the five major cancers by survey in 2016 was 79.7%, and the average cancer screening rates with recommendation was 63.5%. The screening rate for all cancers increased 1.64 times from 2004 to 2016.To promote the quality control of national cancer screening program, several efforts are being performed. The Basic Medical Screening Law was enacted from 2009.The National Screening Advisory Board was established based on this Law. Cancer stage shift is now appearing from 5 targeted cancers. Especially for colorectal cancer, 5-yr survival rate of Korea is estimated to 72.8%, which is the highest on among OECD countries. The trends in 2006-2015 of age-standardized mortality rate of stomach and liver cancers have shown the largest decrease compared to other cancers in Korea. Colon and rectum cancers also have shown a decrease in mortality. Since 1999, the incidence of cervix began to decrease and the incidences of colorectal cancer began to decrease since 2011. The National Screening Program has severalstrength; 1) All the related data are gathered in one system, the National Health Insurance Corporation, 2) National Cancer Registry is collecting cancer incidence data, 3) every subject has own unique ID, 4) So all the data related can be linked using the unique ID.Private sector of the cancer screening is prevalent although data collection from private sector is almost impossible. The benefit and harm of the screening from private sector will be discussed.
Aurelija Vaitkuviene
Vilnius University, Lithuania
Natural fluorescence for cancer diagnosis
Biography:
Aurelija Vaitkuviene, PhD, MD is affiliated Senior Resarcher at Vilnius University. She graduated Vilnius University, defended PhD theses in 1984, later trained at Wensky Laser Centre in Chicago North-West University (USA), at Lund University (Sweden). She is a Founding member of International Academy for Laser Medicine and Surgery (Florence, Italy), Past President of International Society of Laser Surgery and Medicine, and was a President of International Phototeraphy Association (IPTA), served Vilnius University as a representative for European Cervical Cancer Association (ECCA). She has published monograph, more than 40 papers in scientific journals.
Abstract:
Digitalization of human body samples evaluation fits to personalized medicine requirements by person’s and sample data use in diagnostic algorithm. Fluorescence spectroscopy techniques are under intense introduction into the smart applications for everyday life. During 25 year the Institute of Applied Research at Vilnius University was an interdisciplinary science realization structure, and researhers in physics, mathematics, biology and medicine collaborated. International collaboration extended our potential further. Cancer was one of the target areas. Endometrial pathology was an area where chemical dynamics of changes in the tissues was well recongized. Endometrial tissue samples, also endometrial washing were tested by fluorescence spectroscopy to create diagnostic algorithms, based on pathology standards. Both endometrial objects were successfully classified for benign vs malignant condition recognition with proper accuracy. For cervical cancer prevention both in vivo and in vitro fluorescence diagnostics devices and programs were created by local and international resources. While imaging technologies manifested as far-off practical application, the cervical smear spectroscopy revealed as reasonable for at point of care application. The special diagnostic program creation for smear discrimination resulted in automatization of diagnostics, which further could be applied for data clouding and application in remote regions by health care personell. So called “optical biopsy” technology is the example of space science landing on the human utility level, where pure molecular information is classified by “golden standard” of pathology means. So medical experience transfer into modern technology accurs resulting in expansion of highest standards application globally.
Annika Lindström
Uppsala University, Sweden
Prevalence of HPV and HPV-related dysplasia in elderly women
Biography:
Annika Lindström MD, PhD.
Senior consultant obstetrics and gynecology 50% .
Postdoc 50% Center for Clinical research Dalarna, Uppsala University, Clinical Research Center, Faculty of Medicine and Health, Örebro University Sweden.
Earlier worked in hospitals in gynecology Falun and Gävle, and gynecologic oncology Akademiskasjukhuset, Uppsala , Sweden and Radiumhospitalet, Oslo Norway. Doctoral thesis: Prognostic factors for squamous cell cervical cancer, tumor markers, hormones, smoking and S-phase fraction, Umeå University, Sweden 2010. Present research in cervical cancer prevention in elderly women and Urethral Pain Syndrome in women.
Abstract:
Despite a high incidence of cervical cancer (CC) in women over the age of 60, elderly women are not included in the screening programs for cervical cancer prevention. In Sweden, about 30% of CC cases occur in women over 60 and the mortality rate is about 70% in this age group(1-3). Cervical cancer in women above the age of 65 is usually discovered at advanced stages and the prognosis is poor. During the past century, the average life expectancy for women has increased, and many women over 65 are healthy, continue to work, and have an active sex life. There are few studies on HPV prevalence in elderly women.We found an HPV prevalence of about 4 % in this age group and HPV clearance between HPV test one and two was about 40% when the second HPV test was done.Among women with two HPV positive tests there was a high prevalence of high grade intraepithelial neoplasia (HSIL) diagnosed by histology, which motivates screening to continue at older ages. In post-menopausal women, due to hormonal changes, the transformation zone where precursor lesions develop, is situated in the cervical canal and is therefore not accessible for proper examination and sampling. As a consequence Pap smear for conventional cytology or liquid based cytology (LBC), has a low sensitivity and diagnostic surveillance with colposcopy for biopsy has little value. Cytologically-based screening is not meaningful in this age group due to the low sensitivity of this method. The next step would be to introduce repeat HPV testing as a screening method and to find algorithms for sampling strategies such as self-sampling, test intervals and treatment options. Our results can serve as motivation to conduct studies focusing on older women, in order to effectively reduce the prevalence of cervical cancer in this age group.
Dilara SÖNMEZ
Istanbul University, Turkey
The Importance of PDL1-PD1 Genetic Variants in theRisk of Colorectal Cancer
Biography:
DilaraSönmez joins ?stanbulUniversity asanPhd students in the Department of Molecular Medicine Department, Aziz Sancar Institute of Experimental Medicine. She received her MBA from Mustafa Kemal University. Specifically, she is interested in Molecular Biology, genetic and research of cancer and immunity. In her free time, she practices plates, and visiting historical places of the different countries.
Abstract:
PD-L1, which is a member of the B7 family co-inhibitory molecules and the expression level of PD-L1 on colorectal cancer,plays a crucial role in tumour immune escape via impaired cytokine production.PDL1/PD1 polymorphisms were investigated in 181 subjects (87 subjects with CRC and 94 healthy individuals as controls) by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).According to our data, CC, CT and TT genotype frequencies between the patients with colorectal cancer and healthy controls were significantly different (p=0.013). Likewise, in patients vs. controls there was a tendency toward a higher frequency of T allele, p=0.003, Odds ratio (OR): 1.366; 95 %CI 1,05-1,688). It has been found an increased frequency of CT genotype in colorectal cancer patients and this value was statisticaly significance {p=0.042, odds ratio (OR), 1.338; 95% CI 1.008-1.776}. For PDL1; genotype frequencies between the patients with colorectal cancer and healthy controls were not significantly different. The CTAC combined genotype was more common for both colorectal cancer patients and controls (p=0.189). The CCAC combined genotype of the rs2227981variant of the PD1 gene and the rs2890658 variant of the PDL1 gene had a significantly lower frequency in the patient group compared to the control group (p=0.02; OR: 1.170; 95%CI: 1,025-1,336).According to our data, PDL1 was not statistically significant when analyzed alone. However, when PD1 and PDL1 genotypes, were considered together, we think that it could be a biomarker for the risk of colorectal cancer.
Jiye Cai
Macau University of Science and Technology, China
Fabrication, Characterization Of Resveratrol-Loaded Polymeric Nano-Particles And Its Pharmacy Effects
Biography:
Abstract:
Resveratrol is a naturally occurring stilbene and phytoalexin which can be found, for example, in grapes, peanuts, various berries and especially in the Chinese herbal medicine Polygonum cuspidatu. Resveratrol is receiving increasing attention in many fields, such as medicine and pharmacy, in particular because of its reported high anti-proliferative, anti-oxidative and anti-inflammatory activity. It has been described to have beneficial effects in the treatment of diabetes, neurodegenerative disorders, cardiovascular disorders and cancer. Furthermore, it has been found that resveratrol could also attenuate lung vascular hyperpermeability during ventilator-induced lung injury. Thus, it might provide an advantageous option for the treatment of several inflammatory lung diseases like acute lung injury.
Unfortunately, a limited instability, a poor solubility, an inefficient systemic delivery and a low bioavailability often limit the administration of those compounds such as in case of resveratrol.
This work provides in first aspect a method for preparing resveratrol-loaded polymeric nano-particles. These polymeric particles have an average diameter preferably below 1,000 nm. The present work treated a subject suffering from a disease selected from an inflammatory disease or cancer, in particular an acute lung injury. This work comprises the step of administering an effective amount of resveratrol-loaded polymeric particles which have a preselected size and zeta potential and have exceptionally high loading and encapsulation rate of the resveratrol.
These polymeric particles can further provide advantageous water solubility, andhave been characterized an exceptional biocompatibility, especially, allow for a significantly increased bioactivity of the resveratrol. In particular, the modification with modifying polymers comprising and preferably essentially consisting of a poly(ethylene glycol), a chitosan and/or a polyacrylate significantly contributes to the exceptionally improved properties of the obtainable resveratrol-loaded polymeric nano-particles.
These resveratrol-loaded nano-polymeric particles proved to have significantly increased anti-oxidant and anti-inflammation activity compared to particles without the modifying polymers. In particular, these polymeric particles proved to attenuate lung vascular hyperpermeability in vivo, to significantly decrease myeloperoxidase (MPO) activity and to significantly decrease the expression of decisive inflammatory factors, including IL-6, IL-1β, TNF-α in LPS induced ALI model.In particular this work demonstrated the exceptional anti-inflammation activity of resveratrol-loaded polymeric nano-particles compared to the stilbene not loaded on polymeric particles. These resveratrol-loaded polymetric particles can be developed to a new anti-inflammation, anti-cancer medicine.
Mathias Weller
Universidade Estadual da Paraíba (UEPB), Brazil
System delay among patients at two Brazilian breast cancer referral centres and acceleration of patient flow by intervention of non-governmental organizations
Biography:
Abstract:
Background: System delay (SD) is a leading cause of advanced stage of disease and poor prognosis among Brazilian breast cancer patients.
Methods: Cox regression analysis was used to identify variables that contributed to SD among 128 breast cancer patients treated at two public referral centres. Kaplan-Meier analysis was applied to compare time intervals between the first medical consultation and treatment initiation among three groups: 1. Patients in a referral centre with outsourced diagnostic services (FAP); 2. Patients who underwent biopsies and diagnostic mammographies paid for by two non-governmental organizations (FAP-NGOs); and 3. Patients of a referral centre with integrated diagnostic services (HNL).
Results:Women who used a specialized private clinic at the beginning of patient flow had an increased chance (HR = 2.32; 95% CI: 1.17 - 4.60; p = 0.016) of hospital admission within 90 days after the first medical consultation, compared to women who used a public health care provider (HCP). Women who used a public HCP each month and at minimum once a year before diagnosis of disease had a decreased chance (HR = 0.29; 95% CI: 0.12 - 0.71; p = 0.006 and HR = 0.37; 95% CI: 0.15 - 0.91; p = 0.029) of hospital admission within 90 days, compared to women who never used a public HCP. Of 73 and 34 patients of the FAP hospital and the HNL, respectively, 10 (13.7%) and 11 (32.5%) used one HCP prior to hospital admission (p = 0.000).Time between first medical consultation and hospital admission was an average of 515 (SD = 36.6), 370 (SD = 78.2) and 135 (SD = 21.2) days for patients of the FAP hospital, the FAP- NGOs, and the HNL, respectively (p = 0.002).
Conclusions: Women who used a public HCP had an increased SD compared to women who never used them prior to hospital admission and those who used specialized private clinics at the beginning of patient flow.Donation of diagnostic services by the NGOs diminished SD among patients in the FAP. These data suggested that concentration of diagnostic services in one referral centre is superior to outsourcing services.
Rami H. Al-Rifai
United Arab Emirates University, United Arab Emirates
Factors Associated with Lack of Knowledge of Performing Breast Self-Examination and Unawareness of Cervical Cancer Screening Service in Egypt
Biography:
Rami H. Al-Rifai has completed his PhD from Tokyo Medical and Dental University and Postdoctoral studies from Weill Cornell Medical College in Qatar. He is an epidemiologist with broad expertise in epidemiological field and population-based studies utilizing primary and secondary data in field surveys and published studies to generate summary estimates in systematic reviews and meta-analysis. He is an assistant professor of epidemiology at the UAE university. He has published more than 14 papers in in reputed journals.
Abstract:
Background: The incidence of breast and cervical cancers is growing rapidly among Egyptian women. Weassessed the prevalence of, and factors associated withthe lack of knowledgeamong Egyptian females ofperformingbreast self–examination(BSE) and unawareness of cervical smear cancer screening service.
Methods:Secondary data analysis was performed on a representative population-based sample of 7,518 Egyptian females aged 15–59 years from the2015 Egypt Health Issues Survey (EHIS). Crude and adjusted odds ratios (aOR) were used to explore factors associated withbeing unknowledgeable of performing BSEandunawareness of cervical smear cancer screening serviceamongstEgyptianfemales aged 21–59 years.
Results:Mean age of females was 36.9 years with 62% aged between 21–39 years. The proportion of women who were unknowledgeable ofperformingBSEor who were unaware of cervical smear cancer screening service was 87.4% and 92.3%, respectively. After adjusting for potential confounders, young women aged21–29 years (P<0.001), primary education or below (P<0.001), residing in rural areas (aOR, 1.37 and 1.48, P=0.001), accessing different media outlets “not at all or less than once a week” (aOR, 2.81 and 1.46, P<0.05), were associated with a greater likelihood of being unknowledgeable of performingBSEor beingunaware of cervical cancer screening service.
Conclusions: the majority of Egyptian women are unknowledgeable on how to perform BSEor unaware of cervical smear cancer screening service. Multi-media health campaigns arewarranted to raise public knowledgeof the method of BSEand of cervical smear cancer screening service.
Amedeo Piazza
Italy, Italy
Liquid Biopsy: New diagnostic perspectives in glial tumors
Biography:
Abstract:
Glialneoplasms are a group of diseases with a poor prognosis. To date, not all risk factors are known and no screening tests are available. The diagnosis of certainty is still only histological.
Our study aims to verify the hypothesis that exosomal DNA can be used as a diagnostic and prognostic marker.
As already reported in literature, the DNA transported by exosomic vesicles could be an excellent source of informations, because it does not degrade since it is protected by the vesicles. These vesicles seem to represent one of the main mechanisms of tumor remote intercellular signaling used to induce immune-deregulation, apoptosis and both phenotypic and genotypic modifications.
In our study we obtained for eachpatient MRIimaging data, histological data with evaluation for: Ki-67, P53, Mitotic Index, GFAP, ATRX, EGFR, OLIG-2, ATRX, IDH1 and 2, clinical data and a blood samples from which circulating exosomal DNA was extracted through a specific kit.
Our results would demonstrated a relationship between the amount of circulating exosomal DNA and tumor volume with intense mitoticactivity. In addition, particularly high exosomal DNA values were noted in low-grade gliomas. The results are interesting and open new research areas to demostrate the possible role of exosomal DNA in the early diagnosis of recurrent high grade gliomas and asymptomatic low-grade gliomas.
Ugo Rovigatti
University of Florence, Italy
New Modeling for Paediatric Cancer: the Infectious/Viral Hypothesis
Biography:
Dr. Ugo Rovigatti obtained his Ph.D. degree in Molecular Biology with Summa cum Laude in 1973 and in 1999 the Tenured Professorship. From 1979 to 1999 he worked with renown Scientists such as C. Basilico, R. Weiss, H. Varmus, S. Astrin, T. Papas, D. Watson, P. Duesberg, JJ Yunis, J. Bader, J. Trentin, B. Hirt at: ICRF in London, UK; the Rockefeller University in New York; the Fox Chase Institute in Philadelphia; St. Jude Children's Hospital in Memphis, TN; the NCI in Frederick, MD; the Ochsner Foundation-Clinic in New Orleans, LA; the Baylor College of Medicine in Houston, TX.
In 1990-1993, he also worked as scientific consultant (think-tank member) for ARES-Serono CEO F. Bertarelli with Headquarters in Rome and Geneva. When F. Bertarelli died, his son Ernesto got involved in sailing (winning the America’s Cup) and sold A-S to Merck.
Between 1997 and 1999 he was a sabbatical professor in Switzerland (KISPI in Zurich and ISREC in Lausanne). His PI research work has been funded by grants from UICC, ICRETT, SCL, MIUR, MURST etc.
Abstract:
Statement of the Problem: A unifying and acceptable theory is still lacking for human cancer in general and especially in the area of pediatric cancers. Although “Hallmarks of Cancer” (HoC) achieved the goal of unifying several different research areas, this hypothesis predictions were generally falsified. Furthermore, all the consequent therapies (Targeted Therapies-TT) are insufficient.
In recent years, I have suggested an alternative approach of analyzing the essential mechanism(s) of carcinogenesis -and especially of paradoxical cancer cell properties such as Tumor Heterogeneity (TH)-, what I have called “the engine of cancer”. With this magnifying lenses not one (HoC) but 10 alternative models and mechanisms have been extracted from present days cancer research investigations and are currently discussed . An infectious hypothesis for pediatric cancers dates back at least one Century and fits several observations in both clinical and experimental settings. The two most quoted hypotheses: the Population Mixing by L. Kinlen and the Delayed Infection by M. Greaves both acknowledge the potential importance of infections in triggering childhood cALL (most common malignancy in childhood).
Findings: In recent years, we have assessed the role of a novel infectious virus (Micro-Foci inducing Virus or MFV). MFV was isolated from a cancer-cluster of pediatric neuroblastoma cases in Southern Louisiana, characterized by high/extremely high MYCN amplification. MFV causes genetic/genomic aberrations in normal diploid neuroblasts, with induced MYCN DNA-amplifications of 20-100 folds. Furthermore, it induces malignant transformation in vitro and large tumoral masses in vivo.
Conclusion & Significance: Current cancer modeling is limited to an analysis of genomic landscapes, located downstream (i.e. the CANGEN level), while triggering events/mechanisms appear to act upstream (i.e. the UPCAN level). UPCAN mechanisms called Genome-Stripers were recently underlined by us: chromoplexy/chromotrypsis, kataegis, deaminations and the above described MFV induced genomic aberrations.
