Day 2 :
Keynote Forum
Azza Mahmoud Kamel
Cairo University, Egypt
Keynote: Circulating Cell-free DNA (ccf-DNA) in cancer patients: From DNA integrity index to liquid biopsy
Time : 09:00-09:30
Biography:
Azza Mahmoud Kamel is currently working as Emirate Professor of Clinical Pathology at National Cancer Institute, Cairo University, Egypt since 2007. Previously she worked as Professor of Clinical Pathology (1986- 2007) at National Cancer Institute, Cairo University, Egypt, Founder and Head of BMT Lab. Unit (1993- 2007) and Head of Clinical Pathology Department (2005-2007). She pursued her Medical Degree (MB, BCh), Faculty of Medicine, Cairo University (June 1968), Master Degree (MSc) in Clinical Pathology, Faculty of Medicine, Cairo University (October 1972) and Doctorate Degree (MD) in Clinical Pathology(Immunology/ Hematology), Faculty of Medicine, Cairo University (July 1976). She has 165 publications in many reputed journals. She conducted many workshops and completed many research projects. She received many awards like State Award in Medicine (1989), Medal of Excellence from the Egyptian Government (1994). She is an active member of Egyptian Society of Cancer, International Society of Hematology, European and African division (ISH), European Association of Hematology (EHA), American Association of Cancer Research (AACR), International Society of Thrombosis and Hemostasis (ISTH).
Abstract:
Cell-free indicates DNA that is found freely in the blood without a nucleus. Circulating cell-free DNA (ccf-DNAs) were first identified by Mandel and Metais in 1948 but their association with disease was not confirmed till 1977 when their increased level in the plasma/serum of cancer patients was proved. In healthy individuals, the main source of ccf-DNA is apoptotic cells which release uniform DNA fragments 185 to 200 base by a programmed enzymatic cleavage; the level is extremely variable but is usually low to negligible. Cancer cells release different and longer DNA fragments resulting from necrosis, autophagy, or mitotic catastrophe; the chance of an active release from cells was also reported and the levels are much higher than in healthy individuals. However, increased levels of ccf-DNA were observed in many diseases including leukemia, solid tumors, pulmonary embolism, myocardial infarction, tissue trauma, and chronic inflammatory diseases. This broad prevalence of diseases with potentially elevated ccf-DNA levels limits the diagnostic specificity and no cutoff value of plasma DNA concentration produced performance characteristics that would make it a good screening tool for neoplastic diseases. Thus a more refined approach was applied by calculating the ratio between cancer cell-derived ccf-DNA and normal cell-derived ccf-DNA in what is called DNA integrity index. More recently detection of tumor-specific molecular aberrations in the ccf-DNA is performed, what is called liquid biopsy. Many studies reported increased serum concentration and DNA integrity index in various solid tumors including breast, gynecological malignancy, HCC and acute myeloid leukemia. The analysis of the length of circulating DNA in plasma was reported as a sensitive marker for solid tumor detection and it was claimed to discriminate between benign and malignant lesions. The rationale of liquid biopsy is that mutations detected in ccf-DNA are highly specific of cancer and can clearly identify circulating tumor DNA (ct-DNA). Ct-DNA was explored as a prognostic or predictive marker for cancer detection; the studies suggested potential clinical applications. The analysis of ct-DNA ranges in scale from single mutations to whole-genome analyses. Liquid biopsy has many advantages compared to conventional sampling methods. The latter is subject to procedural complications, difficulty in obtaining sufficient material of adequate quality for genomic profiling and sampling biases that arise from genetic heterogeneity. A liquid biopsy is also superior to the conventional monitoring methods namely tumor markers that often lack specificity and imaging which exposes patients to ionizing radiation and has limited resolution. Promising as it is ccf-DNA and ct-DNA assays need scrupulous standardization to overlap discrepancies in sensitivities across various studies. However, sample collection is convenient, minimally invasive, and it avoids the need for tumor tissue biopsies. Analyzes of ccf- DNA and ct-DNA may have the potential to complement or replace existing cancer tissue and blood biomarkers in the future.
Keynote Forum
Ajit Kumar Saxena
All India Institute of Medical Sciences, India
Keynote: Etiopathology of Wilms’ Tumor in India - Genetic Heterogeneity and Increasing “Risk Factor†involving Novel Gene Mutations of MTHFR gene polymorphism
Time : 09:30-10:00
Biography:
Ajit K Saxena has received his PhD (Cytogenetic & Molecular Genetics) from Institute of Medical Sciences, Banaras Hindu University, Varanasi, (U.P) in 1989/90. After receiving his PhD degree he joined NIH funded Indo-US project at AIIMS New Delhi where he identified the role of novel antigen IL6 as a signal traducing agent in human glioblastoma. He retains more than 24 years of academic (teaching/research) experiences in various renowned Institutions of India and abroad. Currently, he is working as a Professor of Clinical Genetics and Head of the Department of Pathology & Laboratory Medicine in AIIMS Patna. Of course, he has published more than 100 articles with high citations. Based on creditability in academics’ he has received several awards and honors, including Gold Medal Award, Confer ‘Vivek Ratan Award’ and Millennium Award from USA and Excellence Award in 2014.
Abstract:
Wilms’ Tumor (WT) is one of the rare tumors of pediatric age group. The etiopathology of WT is complex due to interactions between genetic and environmental factors. Genetic factors include deletion of the q13 region of chromosome-11. The functional aspect of loss of genetic material is unknown but might play a significant role in the process of malignant transformation. “Risk Factors” associated with the development of WT still remain elusive. The rationale behind this study was to identify new mutations and associated “Risk Factors” in the population of Eastern part of India, an area highly susceptible for development of cancer. We performed studies at cytogenetic and molecular level to identify the genetic abnormalities associated with WT cases in comparison with the respective controls. Interestingly, a variety of different karyotypes were observed in the cases of WT that includes the loss of Y-chromosome, presence of ring chromosomes, translocation and numerical (monosomy, trisomy) variations. Further, we evaluated the frequency of WT1/WT2 gene mutation in cases and controls. PCR based analysis demonstrated that the frequency of WT1 (15%) mutation was three times higher than WT2 (5%), which may be due to interaction with environmental factors, or unknown reasons. Further, we performed Methylene Tetrahydrofolate Reductase (MTHFR) C677T gene polymorphism analysis to assess the genetic heterogeneity in WT cases using Amplification refractory mutation system (ARMS)-PCR, where allele “C” changes to “T” (C→T), increasing the “Risk” of the disease. Interestingly, DNA sequencing identified “novel mutations” in MTHFR gene, which has not been reported earlier in cases of WT. Since WT is an embryonic tumor, there may be an involvement of dysfunction of stem cells, therefore we further performed mutational studies to characterize early transcription factors (Sox-2, Oct-4, and Nanog) in WT cases. Such studies were found to be relevant to explore the transforming ability and activation of oncogenes during subtle changes observed during cytogenetics study (deletion, frameshift mutation, translocation and point mutation). The study showed differential expression of Oct-4, and mutation of Sox-2 in WT cases.
Keynote Forum
Wassil Nowicky
Ukrainian Anti-Cancer Institute, Austria
Keynote: Anti-Cancer preparation NSC 631570 (UKRAIN): Modulation of the Immune system
Time : 10:00-10:30
Biography:
Wassil Nowicky, Dipl. Ing., Dr. Techn., DDDr. H. C., Director of “Nowicky Pharma” and President of the Ukrainian Anti-Cancer Institute (Vienna, Austria). Has finished his study at the Radiotechnical Faculty of the Technical University of Lviv (Ukraine) with the end of 1955 with graduation to “Diplom Ingenieur” in 1960 which title was nostrificated in Austria in 1975. He became the very first scientist in the development of the anticancer protonic therapy and is the inventor of the preparation against cancer with a selective effect on basis of celandine alkaloids “NSC-631570”. He used the factor that cancer cells are more negatively charged than normal cells and invented the Celandine alkaloid with a positive charge thanks to which it accumulates in cancer cells very fast. Author of over 300 scientific articles dedicated to cancer research. He is a real member of the New York Academy of Sciences, member of the European Union for applied immunology and of the American Association for scientific progress, honorary doctor of the Janka Kupala University in Hrodno, doctor “honoris causa” of the Open international university on complex medicine in Colombo, honorary member of the Austrian Society of a name of Albert Schweizer. He has received the award for merits of the National guild of pharmacists of America. the award of Austrian Society of sanitary, hygiene and public health services and others.
Abstract:
Unusual for an anticancer agent NSC 631570 possesses some distinct immune properties. The incubation of peripheral lymphocytes of healthy blood donors with NSC 631570 resulted in the increase of lymphocytes with the T-helper phenotype, decrease of the lymphocytes with T-suppressor phenotype as well as an increase of T-helper/T-suppressor ratio. NSC 631570 was administered to nine advanced stage cancer patients (4 with liver cancer, 4 with head and neck carcinomas, and one breast cancer). In three cases the tumors responded partially on the therapy, in one case a minimal response was noted, in 3 cases the disease was stable, and in 2 cases the tumors did not respond on the treatment. After the therapy, the number of T-helper cells (CD4), as well as the CD4/CD8 ratio, increased. In eight oncological patients’ immune parameters were compared before and after the treatment with NSC 631570. It was revealed NSC 631570 affected basically the thymus-dependent cells (T-cells). The number of rosette-forming T-lymphocytes was significantly higher after the treatment. No significant changes were observed in the humoral immune parameters. In nine male lung cancer, patients lymphocytes subpopulations were determined before and after the therapy with NSC 631570. The therapy resulted in increased total T-cells and a reduced T-suppressor fraction. The helper-suppressor ratio normalized. There was no sign of the activation of NK cells, T-helpers as well as B-cells. The restoration of the cellular immunity correlated with the better clinical course of the disease. The effect of NSC 631570 on the functional activity of monocytes from 20 patients with lung cancer or peritonitis was studied using nitro blue tetrazolium chloride test (NBT-test). The authors reported on the positive effect of NSC 631570 on the functional activity of the macrophages as well as antioxidant systems of monocytes and erythrocytes.23 patients with various tumors were treated with NSC 631570 and the immune e parameters were evaluated before and after the therapy. The authors observed the increase in lymphocytes and the decrease of the blood sedimentation rate. Following immune changes were also noted: increase of T-lymphocytes, T-helpers, NK- cytotoxicity, phagocytic activity, normalization of the T-helper/T-suppressor ratio, and occurrence of large granular lymphocytes.
Keynote Forum
Voravud Narin
King Chulalongkorn Memorial Hospital, Thailand
Keynote: The tsunami of immune-oncology in pancreatic adenocarcinoma: success or failure
Time : 10:30-10:50
Biography:
Narin Voravud has completed his MD from Meridol University and clinical residency training from the Department of Medicine, Chulalongkorn University School of Medicine, Thailand, registrar at the University of London, Hammersmith Hospital in London, United Kingdom and hemato-oncology training at the Washington University, St Louis, USA, clinical fellowship in medical oncology, MD Anderson Cancer Center, USA. He has published more than 60 papers in peer-reviewed journals and three textbooks in oncology.
Abstract:
Recent FDA approval for immune checkpoint inhibitors has led to the development of cutting-edge technology in an attempt to cure cancer including genetically modified adoptive immune cell therapy such as CART and TIL cell in refractory ALL and metastatic breast cancer, respectively, achieving complete remission. Unfortunately, many other tumors including metastatic pancreatic cancer is an unmet medical need without any improvement with currently available standard chemotherapy. To evaluate therapeutic efficacy and safety of adding immunotherapy to chemotherapy were retrospectively reviewed in 30 patients with metastatic adenocarcinoma of the pancreas were treated with combination systemic therapy and immunotherapy (immune checkpoint inhibitors, antiHER1 antibody, thymosin-alpha, adoptive NK/ DC vaccine, and immunonutrition) concurrently or sequentially, and compared to the control group who received standard chemotherapy regimens. Clinical benefits (RR, PFS, OS) and immunologic response (CDs, NK cell activity, IFN level) were better in the chemo-immunotarget therapy group. Concurrent treatment is better than sequential therapy. Combination treatment did not Predictive factors of tumor response include nutritional status, performance status, visceral versus lymph node metastases, PDL1 expression, TMB, MSI, and normalization of CD profiles during and after treatment. Cord blood NK cell therapy yields more durable NK cell activity and IFN level than autologous or allogeneic NK cell vaccines, whereas allogeneic NK cell therapy is better than autologous NK cell vaccine. Immunoscore, Next generation CAR-NK cell therapy and powering immune cell mitochondria are under active investigation.
- Natural Methods for Cancer Treatment | Targeted Cancer Therapies| Hematology-Oncology| Oncogenomics |Cancer Pharmacology| Oncology | Cancer Biology | Cancer Screening| Immune Check-point Inhibitors |Cancer Research & Cancer Vaccines
Location: Hillcrest-II
Chair
Marja T Nevalainen
Medical College of Wisconsin, USA
Session Introduction
Ketki Tendulkar
University of Nebraska Medical Center, USA
Title: Effects of newer anti-cancer agents on the kidney
Time : 12:10-12:35
Biography:
Ketki Tendulkar, MBBS is an assistant professor with the Division of Nephrology at the University of Nebraska Medical Center. She has completed her medical school in 1990 from University of Mumbai, India. Thereafter, she came to the United States for further training and completed her residency and fellowship in Nephrology in 2010. After starting as Internal Medicine- Nephrology faculty at the University of Nebraska Medical Center she has published in the emerging field of Onco-nephrology. Her research interests have led to the publications outlined above in this field which deals with cancer-related acute and chronic kidney problems. She is also actively involved in the kidney donor evaluation at the University hospital.
Abstract:
The past few years have seen several important successes in the management of cancer patients with the approval of molecularly targeted agents and immune checkpoint inhibitors for a variety of malignancies. Further, in 2017, we saw the advent of a new form of immunotherapy known as CAR-T cell therapy being developed for hematological malignancies. Despite these advances, our scientists, clinicians, and patients need to be aware that only a small percentage of patients actually benefit from such treatments. Even though the side effect profile of these newer drugs is much better than that seen with the conventional cytotoxic chemotherapy, we cannot overlook the unique, potentially life-altering harmful side-effects associated with these agents. These renal side-effects evolve from the augmentation of the immune system-mediated recognition and targeting of tumor cells. Vascular endothelial growth factor (VEGF) inhibiting agents, such as the monoclonal antibody bevacizumab, and anti-VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs) have the potential to cause elevated blood pressure and proteinuria leading to long-term chronic kidney disease. In addition, there can be off-target effects of these therapies which can range from electrolyte disorders to acute kidney injury. Some others like rituximab, an anti-CD20 monoclonal antibody, and everolimus, a mammalian target of rapamycin (mTOR) inhibitor, can also cause acute kidney injury. Severe acute kidney injury related to cytokine release syndrome, seen with immunotherapy, including CAR-T cells, need aggressive treatment with crystalloid intravenous fluid resuscitation and even renal replacement with dialysis may be indicated. Acute interstitial nephritis is a most common form of renal toxicity with immune checkpoint inhibitors, so far with minimal change, IgA and membranous nephropathy being rarer complications. With increasing options for treating patients with a history of a kidney transplant and cancer, post-kidney transplant rejection can also be an important decision for patients who fear the thought of returning to dialysis. So decision-making regarding stopping or modifying cancer therapy for the overall benefit, despite renal toxicity, continues to remain a challenge. In clinical practice, kidney biopsy to get a tissue diagnosis may be the answer to facilitate management plans in such situations.
Wassil Nowicky
Ukrainian Anti-Cancer Institute, Austria
Title: Affinity of the anti-cancer preparation NSC631570 (Ukraine) to the cancer cells
Time : 12:35-13:00
Biography:
Wassil Nowicky — Dipl. Ing., Dr. techn., DDDr. h. c., Director of “Nowicky Pharma” and President of the Ukrainian Anti-Cancer Institute (Vienna, Austria). Has finished his study at the Radio-technical Faculty of the Technical University of Lviv (Ukraine) with the end of 1955 with graduation to “Diplomingeniueur” in 1960 which title was nostrificated in Austria in 1975. Dr. Wassil Nowicky became the very first scientist in the development of the anticancer protonic therapy and is the inventor of the preparation against cancer with a selective effect on basis of celandine alkaloids “NSC-631570”. He used the factor that cancer cells are more negative charged than normal cells and invented the Celandine alkaloid with a positive charge thanks to which it accumulates in cancer cells very fast. Author of over 300 scientific articles dedicated to cancer research. He is a real member of the New York Academy of Sciences, member of the European Union for applied immunology and of the American Association for scientific progress, honorary doctor of the Janka Kupala University in Hrodno, doctor “honoris causa” of the Open international university on complex medicine in Colombo, honorary member of the Austrian Society of a name od Albert Schweizer. He has received the award for merits of National guild of pharmacists of America. the award of Austrian Society of sanitary, hygiene and public health services and others.
Abstract:
It is well known all living cells have a membrane potential of about -60 to –100mV. The negative sign of the membrane potential indicates that the inside surface of the cell membrane is relatively more negative than the immediate exterior surface of the cell membrane. Researchers at the University of Natural Resources and Life Sciences, Vienna (Austria) revealed human osteosarcoma cells to have a high capacity to absorb NSC631570 while absorption in normal endothelial cells was considerable lower under the same experimental conditions. This selective uptake of NSC631570 in the cancer cells has been confirmed due to its unique prop-erty to auto fluorescence under UV light. A study examined how NSC631570 affects the electro kinetic potential (EKP) of malignant and benign cells. The EKP of the Ehrlich’s carcinoma cells dropped after incubation with NSC631570. The EKP decrease of normal cells was less pronounced. The cytotoxic effect of NSC631570 was examined on two primary pancreatic cancer cell lines (PPTCC), fibroblasts from ductal pancreatic cancer tissue samples (F-PDAC) and an immortalized ductal epithelial pancreas cell line (HPNE). Cytotoxicity was established by means of Cell Titer 96 kit. In the tests with primary pancreatic cancer cell lines the modulation of NSC631570 absorption in the medium was determined with the help of the fluorescence of NSC631570 under UV light. The fluorescence test showed that carcinoma cells absorbed more of the preparation than fibroblasts and normal epithelial cells. The selective accumulation of NSC631570 in the cancer cells explains its favorable safety profile and high therapeutic index of 1250.
Narjiss Akerzoul
Mohammed V University Of Rabat, Morocco
Title: Oral Mucocitis: A very common oral side effect of radio-chemotherapy
Time : 14:00-14:25
Biography:
Narjiss Akerzoul received her Doctorate of Dental Surgery (DDS) from Mohammed V University of Rabat-Morocco in the year 2011. Later she worked as a General practitioner Dentist in Oral Health Center of Guelmim City, Morocco. Later in 2013, she started her residency program in Oral Surgery and Oral Medicine and OroFacial Pain in the Consultation Center of Dental Treatments of Rabat. Later on, she completed her Diploma in Biostatistics and Research Methodology during 2014-2015. She achieved her Board examination of Oral Surgery and Oral Medicine and OroFacial Pain in July 2017 and became An Oral Surgeon Fellow. She has authored and co-authored many International Publications in the field of Oral Surgery, Oral Medicine and Oral Oncology. She has been an editorial member in Department of Oral and Maxillofacial Surgery of the International Journal of Oral Health and Medical Research (IJOHMR), Reviewer and Editor in Omics Group Biomedical Journal. .
Abstract:
Introduction: Oral mucositis is a frequent adverse effect of cytotoxic treatments by chemotherapy or radiotherapy. At the moment, there is no validated consensus for preventive or curative care.
Aim: To carry out a state of the management of chemo-induced mucositis.
Materials and Methods: Our study is a retrospective observational one, carried on 40 patients in two departments: dental service, and radiotherapy service of the National Institute of Oncology (INO) of Rabat, as well as in the Oral Surgery department of the Consultation Center of Dental Treatment of Rabat. The included patients were treated with radiotherapy +/- highly mitogenic chemotherapy. The evaluation criteria were: Age, sex, living environment, oral health, type of cancer treatment and others.
Results: Among the 40 patients included, 5 subjects developed mild grade 1 mucositis, grade 2 interested a group of 17 subjects, 14 patients developed grade 3 mucositis, and finally 4 subjects developed severe grade 4 mucositis. Preventive treatment was introduced in only 11 patients. Of the 40 cases, 33 were treated with curative treatment.
Discussion: After analysis of the results, there was no correlation between the type of pathology treated, the cytotoxic treatment used and the management modalities of the mucositis.
Conclusion: Although the results were very disparate, they will enable us to evolve the practices, validating proposals of protocols of care in a multidisciplinary working group. A new study could then be carried out to evaluate the effectiveness of these protocols.
Joseph C Glorioso
University of Pittsburgh School of Medicine, USA
Title: Herpes simplex virus oncolytic vectors (oHSV) armed with the NKG2D ligand ULBP3 enhances treatment of gliomas
Biography:
Joseph C Glorioso began his career at the University Of Michigan School Of Medicine, Ann Arbor, MA, USA (1976–1989), where he became Professor of Microbiology and Immunology and Assistant Dean for Research and Graduate Studies. He subsequently moved to the University of Pittsburgh, School of Medicine, and Pittsburgh, USA, where he served as Chair and the McElroy Professor of Biochemistry until 2009. He is a former president of the American Society of Gene and Cell Therapy and serves as the American Editor of Gene Therapy. His research focuses on molecular genetic aspects of herpes simplex virus (HSV) pathogenesis and the development of HSV gene vectors for treatment of chronic pain, neuropathy, and cancer.
Abstract:
Glioblastoma (GBM) is an incurable brain tumor for which the standard of care is not effective. Oncolytic viral therapies are under development to destroy GBM using engineered viral vectors that preferentially replicate in tumor cells. Although early phase trials have reported sporadic successes, improvements in vector design are needed to improve therapeutic efficacy. Effective viral therapy requires vectors that induce virolysis and promote anti-tumor immunity. This outcome is particularly challenging in GBM because glial malignancies are immunologically cold, and embedded in a profoundly immunosuppressive microenvironment. We have focused on the development of oHSV because these vectors (i) are highly virolytic for GBM, potentially releasing immunogenic cell debris, (ii) can be rendered safe without compromising virus lytic activity and (iii) can be engineered to express multiple immunomodulatory transgenes capable of activating innate and acquired anti-tumor responses. Here we describe an advanced oHSV vector armed with ULBP3, an activating NK cell (NKG2D) ligand that is often down-regulated as an immune escape mechanism in glioma. We tested the hypothesis that the expression of ULBP3 from an oHSV could activate NK cells and thereby improve the efficacy of GBM oncolytic virotherapy. Using human-derived glioma stem cells and a mouse glioma cell line, we demonstrated that infection of multiple cell lines with oHSV-ULBP3 significantly improves NK cell-mediated cytolysis in vitro. We then tested the therapeutic efficacy of an oncolytic vector armed with ULBP3 in a xenogeneic nude mouse model using the GBM-30 human glioma cell line. We observed that this new vector displayed an improved therapeutic profile compared to the parental unarmed vector (80% vs 40% long-term responders). Further studies using a GL261N-based orthotopic syngeneic model demonstrated that ULBP3 expression induced infiltration of cytotoxic CD8 T cells, suggesting that ULBP3 can be a potent inducer of both innate and acquired immunity. Our ongoing studies will determine whether a ULBP3 expression can enhance long-term animal survival in an NK cell or CD8 T cell-dependent manner.
James Vaidyan
Ayurveda Vaidyasala, Center for Cancer Treatment, India
Title: Indian treatment for Leukemia and other cancers
Biography:
James Vaidyan is a traditional Ayurveda Vaidya with experience of more than 40 years in treating different diseases including cancers. (Vaidya means traditional doctor.) he is a doctor for many generations, holding through many generations, leaves which are detailing esoteric Vedic science of life. He treated and cured many patients suffering from bad stages of leukemia and other kinds of cancers.
Abstract:
I am a traditional Ayurveda practitioner (Vaidya) treating different types of cancers and leukemia. Chemotherapy can be avoided by opting for Ayurveda treatment. Remission is faster, without debilitating negative side effects. An intricate course of repeated refining, elaborate processing, and enrichment of highly efficient manner. A patient recovering from diseases through such treatment is becoming refined physical being and the body system totally regenerated. The basic principle of the methodology of this treatment is to strengthen and equip our own T cells in the blood; they become capable to fight against cancer. Antibody proteins are produced automatically and destroy cancer cells, without damaging other parts of the body. Medicines are prepared through elaborate processing. We are following the same procedures that have been practiced by the ancient Maharishis and masters. I have treated many cancer patients- different types of cancers including leukemia. Patients are improving much faster than what is happening in the best hospitals anywhere in the world. Even in salvage treatment, patients come back to life. The quality of life that they are enjoying during and after the treatment is tremendously different from how cancer patients live and suffer under chemotherapy and radiation treatment. It is my sincere request to the international scientific community to focus on how these practices that lie outside conventional science may be appropriately utilized and further researched. I am seeking right people/ Universities /Research Institutions for Collaboration and knowledge transfer for better utilization of this knowledge for the benefit of entire humanity.
Ozge Sezin Somuncu
Bahcesehir University, Turkey
Title: Exosomes of human melanoma cells induce cancer development in human dermal cells through rab27a and c-met
Biography:
Ozge Sezin Somuncu has completed her PhD in the year 2017 at the age of 25 years from Yeditepe University/Turkey. She had a short post-doctoral fellowship in Queen Mary University London and shortly after she had an offer to develop her career as an assistant professor in Turkey. She is currently an Assistant Professor at BahçeÅŸehir University Faculty of Medicine. She is also the principal investigator of SOMUNCU Lab. Se has published 4 papers in reputed journals, 6 submitted manuscripts in 2018, she also has an accepted patent application, running 10 projects and applied for a COST Action. She has been serving as a reviewer in the Journal of Psychiatry and Psychopharmacology. She has collaborations with Queen Mary University London and Harvard Medicine Opthalmology Department.
Abstract:
Exosomes are small membrane-derived vesicles that transmit DNA constituents, mRNAs, microRNAs and proteins from donor cells to a receiver cell. Many divergent cells comprising mesenchymal cells, immune cells, and cancer cells discharge exosomes. Studies show that cancer cell exosomes create the entry and reprogramming of essentials connected to the tumor environment. A reference study established that melanoma-derived exosomes convey diverse proteins such as c-Met and Rab27a, which indicate a melanoma mark. Increased Met expressions in serum exosomes have thought to be a predictor of disease progression. Meanwhile, Rab27a has identified to be important in exosome discharge. Decreased expressions of Rab27a in human melanoma cells determined to diminish exosome release. This project aims to examine the effects of downregulation and upregulation of Rab27a and c-Met in human melanocytes by utilizing the isolated exosomes from a malignant melanoma cell lineage. Throughout the analysis of cancer-like formation; different protocols covering gene transfections, flow cytometry analysis of the transfection efficiency, Annexin-V apoptosis assays, tube formation assays, ELISA assays and gene expression profiling were performed. According to the results, exosomes derived from cancer cells conveyed information to healthy melanocytes/keratinocytes and induced cellular reaction with Met and Rab27a overexpression, therefore silencing their genes may be a beneficial approach for future treatment possibilities. The developing molecular contextual of melanoma exosomes and their implications for improved management of melanoma patients can be an astonishing therapeutic methodology for future actions.
G Aguirre
Hakken Enterprise S.A. de C.V., Mexico
Title: GanplexTM and Kimera-TestTM : Biotechnological screening tools designed identify human cancer-related virus and SNPs in non-invasive samples
Biography:
Gisela Aguirre (MSc and PhD in Genetics & Molecular Biology), with bold principles and values, bets for the creation of a new paradigm of developing Science in Mexico. During the last five years, she has dedicated her talent and energy to the creation of a young scientific team and a has become Founder & CEO of startups in Mexico and USA, with more than 20 people dedicated to the development of technologies for affordable in vitro diagnostics tools for HIV, HPV, respiratory and gastric pathogens, aneuploidies in human embryos and cancer genetic propensity detection..
Abstract:
Most efforts of allopathic medicine are directed to treat diseases. This path has proved to be costly when chronic diseases, such as cancer and its associated viral co-morbidities, need to be treated and monitored in the long term. Hence, the development of prevention-oriented medicine may reduce the magnitude of the financial burden associated with practicing remedy-based medicine. GanplexTM and Kimera-TestTM, the prime products of Hakken Enterprise, were then conceived to identify individuals with high genetic risk of developing cancer before the disease becomes symptomatic. GanplexTM and Kimera-TestTM take advantage of DNA extracted from saliva and urine samples to identify cancer-related viruses and SNPs through multiplex assays in a single reaction. At the current stage of development, both assays identify cancer-related SNPs and the viral sequences with a sensitivity, specificity, and confidence higher than those reported for Sanger’s sequencing. Both assays require small DNA quantities to begin with and no purification of PCR products prior hybridization. This shortens to approximately 7 hours the time to provide a result. Hence, GanplexTM and Kimera-TestTM are biotechnological tools that provide the genetic information needed to identify individuals under risk of developing cancer, a circumstance that would help in personalizing cancer preventing protocols and introducing precision medicine into everyday’s life. This work was financed by CONACyT (Grant No. 250884, 230066).
Narjiss Akerzoul
Mohammed V University Of Rabat, Morocco
Title: Kaposi sarcoma and human herpus virus type 8: A rare case and review of the literature.
Biography:
Narjiss Akerzoul received her Doctorate of Dental Surgery (DDS) from Mohammed V University of Rabat-Morocco in the year 2011. Later she worked as a General practitioner Dentist in Oral Health Center of Guelmim City, Morocco. Later in 2013, she started her residency program in Oral Surgery and Oral Medicine and OroFacial Pain in the Consultation Center of Dental Treatments of Rabat. Later on, she completed her Diploma in Biostatistics and Research Methodology during 2014-2015. She achieved her Board examination of Oral Surgery and Oral Medicine and OroFacial Pain in July 2017 and became an Oral Surgeon Fellow. She has authored and co-authored many International Publications in the field of Oral Surgery, Oral Medicine and Oral Oncology. She has been an editorial member in Department of Oral and Maxillofacial Surgery of the International Journal of Oral Health and Medical Research (IJOHMR), Reviewer and Editor in Omics Group Biomedical Journal.
Abstract:
Kaposi sarcoma (KS) is a multifocal angioproliferative disorder of vascular endothelium, usually described in HIV positive patients, and primarily affecting mucocutaneous tissues with the potential to involve viscera. Four clinical variants of classic, endemic, iatrogenic, and epidemic KS are described for the disease, each with its own natural history, site of predilection, and prognosis. All forms of Kaposi sarcoma may manifest in the oral cavity and Kaposi sarcoma-associated virus (KSHV), also known as Human Herpes Virus type 8, appears essential to the development of all clinical variants. In the absence of therapy, the clinical course of KS varies from innocuous lesions seen in the classic variant to rapidly progressive and fatal lesions of epidemic KS. Our case report provides an overview of clinical aspects, pathogenesis, and treatment about a non-HIV positive patient presenting the classic form of KS related to HHV8.
Karine Breckpot
Vrije Universiteit Brussel, Brussel
Title: TriMix and antigen mRNA based vaccination
Time : 16:45-17:10
Biography:
Karine Breckpot has completed her PhD on genetically engineered dendritic cell vaccines in 2004 at the VUB (Belgium) and continued this line of research during her postdoctoral studies performed at VUB (Belgium) and the University College London (UK). She is a tenure track professor at the VUB, member of the faculty and research board, and president of the ethical committee for use of laboratory animals. She is a recognized expert in the field of immunotherapy as evidenced by her list of publications, patents, invited lectures, awards and presence in grant review committees.
Abstract:
Our immune system can detect and destroy cancer cells. However, growing cancer cells camouflage themselves as well as possible, blocking the attack of the immune system, or worse, they hijack certain cells of the immune system and turn them into cancer-promoting cells. In an attempt to stop this process, scientists want to boost the immune system. This can be done through cancer vaccination. The rationale is to provide the immune system with the identification card of cancer cells (tumor antigens) as well as an adjuvant to alarm the immune system. Several cancer vaccination strategies have been developed, among which the use of dendritic cells engineered in the laboratory using mRNA. We studied mRNA as a tool to deliver tumor antigens and immune modulating proteins, in particular, a mix of three mRNA molecules encoding the co-stimulatory molecule CD70 and two DC activation stimuli, CD40 ligand, and active TLR4 referred to as TriMix mRNA. Vaccination of stage III/IV melanoma patients with this dendritic cell vaccine have proven to be safe and well tolerated, to induce tumor antigen-specific immune responses and more importantly to induce objective clinical responses in over a quarter of patients. Although promising, ex vivo engineered cell-based vaccines are patient-specific and therefore time and money consuming. To generate a widely applicable cancer vaccine, it is important to immediately activate the dendritic cells in the patient's body. Therefore we studied several ways to deliver tumor antigen and/or TriMix mRNA to dendritic cells in situ. We studied several routes of delivery, including intranodal, intratumoral and intravenous. Linked to the systemic delivery of mRNA we studied several modes of mRNA encapsulation, including the use of lipids and polymers. The results of these studies will be presented and discussed in view of the current state-of-the-art.
- Pediatric Oncology | Oncology | Chemotherapy | Skin Cancer | Cancer Therapy | Cancer Biology | Cancer Screening | Cancer Prognosis & Diagnosis | Cancer Immunology & Immunotherapy | Immuno- Oncology Studies | Tumor Immunology
Location: Hillcrest-II
Chair
Ashok Srivastava
ClinFomatrix, USA
Session Introduction
Narjiss Akerzoul
Mohammed V University Of Rabat, Morocco
Title: Burkitt lymphoma: a successful chemo-sensible malignant process
Biography:
Narjiss Akerzoul received her Doctorate of Dental Surgery (DDS) from Mohammed V University of Rabat-Morocco in the year 2011. Later she was working as a General practitioner Dentist in Oral Health Center of Guelmim City, Morocco. Later in 2013, she started her residency program in Oral Surgery and Oral Medicine and OroFacial Pain in the Consultation Center of Dental Treatments of Rabat. Later on, she completed her Diploma in Biostatistics and Research Methodology during 2014-2015. She achieved her Board examination of Oral Surgery and Oral Medicine and OroFacial Pain in July 2017 and became An Oral Surgeon Fellow. She has authored and co-authored many International Publications in the field of Oral Surgery, Oral Medicine and Oral Oncology. She has been an editorial member in Department of Oral and Maxillofacial Surgery of the International Journal of Oral Health and Medical Research (IJOHMR), Reviewer and Editor in OMICS GROUP Biomedical Journals. Her research includes Oral Surgery, Oral & Maxillofacial Surgery, Oral Medicine, Oral Oncology, Head & Neck Oncology, Oral Implantology, Oral Infectious Diseases.
Abstract:
Burkitt's lymphoma is a rare form of malignant non-Hodgkin lymphoma mature B cells. In Europe and North America, representing about half of non-Hodgkin lymphomas in children and about 2% of those in adults. Indeed, two incidence peaks exist: the first is in childhood/adolescence/early adulthood and the second after 40 years. Male individuals are preferentially affected. Patients infected with the HIV virus and that the antiviral therapy is not optimal are particularly susceptible to developing Burkitt's lymphoma. Two forms exist: one is called "endemic" (subtropical Africa) and linked to the Epstein Barr Virus (EBV). Diagnosis is based on biopsy of a mass or puncture of an effusion or bone marrow revealing the presence of tumor cells. The staging is performed using imaging (mainly ultrasound and scanner). Differential diagnosis includes other forms of child abdominal tumors (such as Wilms' tumor and neuroblastoma. The management should be done in a specialized center in oncology/hematology. The treatment is based on chemotherapy which is some months but intensive. Our clinical observation reports the case of a girl aged 13 who presented with severe oral manifestations of budding Burkitt lymphoma having evolved after 2 years of treatment.
Doaa A Saleh
Cairo University, Egypt
Title: Effect of nutritional counseling on quality of life of breast cancer patients: An intervention study
Biography:
Doaa A Saleh, MD, PhD; graduated from the Faculty of Medicine, Cairo University in Egypt in1996. She completed her PhD in the year 2005 from Cairo University, Egypt. She also completed the Clinical Nutrition Diploma in 2008 from Cairo University. She is Professor of Public Health, Preventive and Community Medicine at the Faculty of Medicine, Cairo University since 2011. She is also the Director of Medical Records and Hospital Statistics Department at Cairo University Teaching Hospitals. She teaches epidemiology and public health and leads research in communicable and non-communicable diseases as well as health systems research. Her research interests include the epidemiological features and the prevention and control of cancer, obesity and infectious diseases. She was the principal investigator and Co-investigator of a number of nationally and internationally funded research projects. She has more than 30 publications in peer-reviewed journals.
Abstract:
The aim of this study was to assess the effect of nutrition counseling (NC) on the quality of life (QoL) of breast cancer patients (grade 2) receiving chemotherapy. A total of 100 patients were enrolled in the study, where 50 patients were assigned to the NC group and 50 patients to the control group. NC group received four NC sessions over 6 weeks. QoL assessment was done at baseline, and then after two and three months using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30). The EORTC QLQ-C30 version 3.0 is a 30-item core cancer-specific questionnaire measuring QoL in cancer patients and incorporates five functional scales; physical (PF), role (RF), cognitive (CF), emotional (EF) and social (SF), three symptom scales for fatigue, pain and nausea/vomiting, a global health QoL scale, and several single items for the perceived financial impact of disease and treatment and for the assessment of additional symptoms such as dyspnoea, appetite loss, sleep disturbance, constipation and diarrhea, which are commonly reported by cancer patients. At baseline, no significant difference was found in the symptom scales and in 2 of the functional scales (EF and CF) between the NC and control group (p>0.05). However, three functional scales (PF, RF and SF) and the global health QoL scale were significantly higher among the control vs. NC group (p<0.05). At 2 and 3 months after the intervention; PF, RF, CF, and EF and all symptom scales (except constipation) showed significant progressive improvement among both NC and control groups (p<0.05). However, the percent change of these scales was significantly higher among the NC group when compared to the control (p<0.05). Unlike controls, NC group showed significant progressive improvement of global health QoL scale, as well as SF, constipation and dyspnea scales (p<0.05). Though insignificant, yet Financial difficulties’ scale showed slight improvement among both NC and control groups (p>0.05).
Nidhi Abraham
VIC, La Trobe University, Australia
Title: Molecular mechanisms involved in acquired chemotherapeutic drug resistance to 5-FU in colorectal cancer
Biography:
Abstract:
Nidhi Abraham
VIC, La Trobe University, Australia
Title: Molecular mechanisms involved in acquired chemotherapeutic drug resistance to 5-FU in colorectal cancer
Biography:
Nidhi has completed her Master’s in Biotechnology and Bioinformatics from La Trobe University, Melbourne, Australia and is currently in her final year of PhD. She also has experience of 3 years as a Research Assistant in National AIND Research Institute (NARI), India.
Abstract:
Colorectal cancer (CRC) is the third and second most common cancer in males and females respectively and has the third highest mortality rate reported worldwide. In patients with metastatic CRC, chemotherapy is the current approach taken to treat the patients. The most common drug used for the treatment is 5-Fluorouracil (5-FU) by itself or in combination with other drugs. However, the cells develop resistance to the drugs resulting in treatment failure. Even though the molecular mechanisms regulating chemoresistance is critical, it is poorly understood. Here, to study the mechanisms involved in chemoresistance, a panel of 7 CRC cells resistant to 5-FU was generated by continuously growing the CRC cells in the presence of the drug. Parental and 5-FU resistant CRC cells were assayed for regulators of acquired chemoresistance to 5-FU using quantitative proteomics, DNA methylation, and biochemical experiments. The assays revealed several mechanisms contributing to acquired drug resistance including epithelial-to-mesenchymal transition (EMT), deregulated apoptotic and signaling pathways, senescence and increased survival autophagy. With the aim to target proteins involved in these mechanisms, a combination of inhibitors and CRISPR based gene knockout techniques were used to sensitize the 5-FU resistant cells. Among these, inhibitors to late autophagy could sensitize the 5-FU resistant cells while the other mechanisms including EMT were observed to be by-stander effects which did not affect the sensitivity of the resistant cells. Hence, inhibiting autophagy in combination with 5-FU can be a potential treatment avenue for CRC patients exhibiting resistance to chemotherapy, thereby aiding in overcoming chemoresistance and improving their survival rates.
Sarah J Vitug
University of Queensland, Australia
Title: A practical guide to the treatment of melanoma during pregnancy
Biography:
Sarah J Vitug is a native of San Diego, CA where she double majored in BS Biopsychology and BA Communications from the University of California, Santa Barbara 2012, then went on to earn a Masters in Education from Loyola Marymount University 2013. She currently is a 3rd year Intercalated MD-MPhil student at the University of Queensland Faculty of Medicine, Ochsner Clinical School. Research experiences from surgical oncology department at John Wayne Cancer Institute (Santa Monica, CA), surgical oncology department at Melanoma Institute Australia (Sydney, AUS), anesthesia and pain medicine department at St. Vincent’s Hospital (Melbourne, AUS), experimental dermatology department at UQ Diamantina Insitute (Brisbane, AUS), and bioinformatics department at Ochsner Medical Center (New Orleans, USA). 2015 International Association of Student Surgical Symposium–Best Oral Presentation Award Winner; 2017 Three Minute Thesis Winner. 2017 certification of completion in Network Analysis in Systems Biology with bioinformatics application at Ochsner Medical Center (New Orleans, USA). Research interests: experimental dermatology, pregnancy-associated melanoma, and surgical oncology.
Abstract:
Melanoma is one of the most common cancers among women of childbearing age, and therefore one of the most prevalent malignancies diagnosed during pregnancy. With advanced maternal age becoming more commonplace, the likelihood of being diagnosed with a melanoma during pregnancy naturally increases. Controversy over whether the pregnancy is associated with more aggressive melanoma progression exists in the literature, thus a case study on JC, a 31 year old female diagnosed with a 7mm level V melanoma in her left popliteal region at 17 weeks gestation is provided in which this manuscript will expound upon. Following sentinel lymph node biopsy, the patient was found to have 2/10 nodes positive for metastatic melanoma upon left inguinal dissection. Due to the nature of her advanced disease, JC’s care was presented at the Melanoma Institue’s multidisciplinary team (MDT) meeting where detailed discussions on adjuvant radiation and systemic therapy were invaluable for JC’s treatment plan. In light of her third-trimester pregnancy, all elements of JC’s management prioritized the delivery of a healthy term infant. Following delivery, JC was evaluated with PET imaging that identified her disease progression to stage IV melanoma with lung, liver and subcutaneous lesions. Thus treatment for her terminal illness remained central to subsequent MDT meetings. The aim of this manuscript is to establish a set of practical guidelines for treating melanoma in pregnant women. Treating melanoma with a coinciding pregnancy can be a challenging task due to increased risks to the fetus, thus a multidisciplinary approach is crucial for safe and effective management. Procedural considerations for excision biopsy or local resection on a pregnant patient must take into account patient positioning, choice of antiseptic prep and local anesthetic, the necessity of sentinel lymph node biopsy, and timing of surgery. It is imperative to be cognizant of the decisions made during management of disease during pregnancy as it may potentially have lethal effects on not only the patient but the fetus.
Samir Mehndiratta
Taipei Medical University, Taiwan
Title: Anti-metastatic activity of Albizia lebbeck stem bark extract against breast cancer cell lines
Biography:
Samir is a postdoctoral research fellow in Department of Medicinal Chemistry at Taipei Medical University (TMU), Taiwan. He has his expertise in small molecules as potent anticancer compounds and his work accentuates on designing and synthesizing inhibitors of various epigenetic modulations like HDAC inhibitors, HAT Inhibitors, target based therapy, designed multiple ligand (DML) based drug design and personalized medicines for the treatment of cancer. During his doctorate, he received QS-Apple Scholarship 2014 for outstanding research and social engagements. With high impact papers in various research journals he has been awarded with Outstanding Postdoctoral Award for year 2016 and 2017 from TMU and has also received Young Research Scientist Award 2018 from SBMLS (India).
Abstract:
Histone acetylation finds its roots in the 1960s when it was recognized that acetylation of histones and remodeling of the compact chromatin structure is associated with gene induction. Histone deacetylases (HDACs) display multifaceted functions by coordinating the interaction of signal pathways with chromatin structure remodeling and the activation of non-histone proteins; these epigenetic regulations play an important role during malignancy progression. This initiated a quest for development of inhibitors of histone deacetylase (HDAC) as novel drug candidates. We have designed and evaluated a series of potent phenyl acrylamides, based on the core structure of PXD101 and LBH589, demonstrating potent HDAC inhibition and anti-inflammatory and anti-cancer effects. The synthesized compounds are found to be endowed with potent Hela Nuclear HDAC inhibitory activity, almost 2.5 folds to 42 fold better than SAHA. Synthetics exhibited significant inhibitory effects on various cancer cell lines with GI50 values in the range of 0.02 to 0.35 μM which are 10-50 folds better than SAHA (Vorinostat). N-hydroxy-3-{4-[2-(2-methyl-1H-indol-3-yl)-ethylsulfamoyl]-phenyl}- acrylamide (MPT0G157) treatment significantly inhibited different tumor growth at submicromolar concentration and was particularly potent in human colorectal cancer (HCT116) cells. Apoptosis and inhibited HDACs activity induced by MPT0G157 was more potent than that by the marketed drugs PXD101 (Belinostat) and SAHA. In an in vivo model, MPT0G157 markedly inhibited HCT116 xenograft tumor volume and reduced matrigel-induced angiogenesis. The anti-angiogenetic effect of MPT0G157 was found to increase the hyperacetylation of heat shock protein 90 (Hsp90) and promote hypoxia-inducible factor-1α(HIF-1α) degradation followed by down-regulation of vascular endothelial growth factor (VEGF) expression. Our results demonstrate that MPT0G157 has potential as a new drug candidate for cancer therapy.
Biography:
Andrei L Gartel, PhD, is an Associate Professor in the Department of Medicine at the University of Illinois at Chicago and is the academic editor of PLOS ONE. He is the author of 90 peer-review publications that include more than 25 reviews. He has more than 11,000 citations and his h-index is 41. His scientific interests include cancer, regulation of oncogenic transcription factors FOXM1, protein-protein interactions; cell cycle and regulation of CDK inhibitor p21. Specifically, his lab is interested in the identification of new FOXM1 inhibitors. He received his funding from NIH, DOD and private companies/foundations.
Abstract:
FOXM1 is an oncogenic transcription factor that is overexpressed in the majority of human cancers and is a potential target for anticancer drugs. We identified proteasome inhibitors as the first type of drugs that target FOXM1 in cancer cells. Moreover, we found that HSP90 inhibitor PF-4942847 that does not act as proteasome inhibitor also suppresses FOXM1. Chaperone HSP70 is induced after treatment with both proteasome/HSP90 inhibitors and after heat-shock stress and we identified this chaperone as a novel negative regulator of FOXM1 after proteotoxic stress. We showed that FOXM1 and HSP70 interact in cancer cells following proteotoxic stress and FOXM1/HSP70 interaction led to inhibition of FOXM1. We have previously shown that FOXM1 interacts with nucleophosmin (NPM) in cancer cells and NPM determines the cellular localization of FOXM1. Mutations in NPM1 result in cytoplasmic re-localization of NPM (NPM1mut) and favorable outcome for the patients. We found the evidence that improved outcomes in the subset of NPM1mut AML may be partially explained by the cytoplasmic re-localization and consequent functional inactivation of FOXM1. First, we confirmed the co-localization of FOXM1 and NPMmut in the cytoplasm of AML patients bone marrow biopsies and determined a strong cytoplasmic expression of FOXM1 only in NPM1mut AML cells. We also showed an important role of FOXM1 in chemo-resistance in leukemia cell lines with nuclear, but not cytoplasmic FOXM1. These data imply that suppressing of FOXM1 in AML could increase sensitivity to standard chemotherapy.
Sujata Maiti Choudhury
Vidyasagar University, India
Title: Cytotoxic, apoptotic and tumor regressive efficacy of PLGA encapsulated diosgenin nanoparticles in cancer cell lines
Biography:
Sujata Maiti Choudhury is a Professor and In-charge of Biochemistry, Molecular Endocrinology and Reproductive Physiology Laboratory in the postgraduate Department of Human Physiology with Community Health of Vidyasagar University, West Bengal, India. She completed her M.Sc. in Physiology in 1986 and M.Phil. Degree in Environmental Science in 1988 from University of Calcutta, Kolkata. She was awarded Doctor of Philosophy in 1995 from Jadavpur University, Kolkata. She was also graced as the Founder Director of Women’s Studies Centre, of Vidyasagar University (2010-2015). She is a Life member of Indian Science Congress of India, Indian Association of Cancer Research (IACR), Physiological Society of India, Kolkata, and South Asian Association of Physiologists. She is acting as a reviewer for many journals including Nanotoxicology (Taylor & Francis), Food and Chemical Toxicology (Elsevier), Journal of Basic Microbiology (Wiley-VCH), Drug and Chemical toxicology (Taylor & Francis) etc.
Abstract:
Cancer is a universal public health problem as it is one of the main causes of morbidity and mortality worldwide. Polylactic-co-glycolic acid (PLGA) nanoparticles, one of the most effective biodegradable polymeric nanoparticles, are approved by the US FDA to use for the encapsulation of various cancer-related drugs and their successful delivery in vivo due to its controlled and sustained release properties, low toxicity, and biocompatibility. Diosgenin (DGN), a steroidal saponin phytocompound, plays a predominant role in decreasing cell malignancy and inhibits tumor promotion reducing matrix metalloproteinases expression and inducing apoptosis through cell cycle arrest, activation of p53 and caspase-3 but DGN has many limitations in clinical application due to its poor solubility and low bioavailability. The present study was designed to synthesize PLGA encapsulated diosgenin nanoparticles (PLGA-DGN NPs) and to evaluate its anticancer efficacy. The PLGA-DGN nanoparticles exhibited high entrapment efficacy (73.8%), and a higher blood circulation half-time as well as sustained release kinetics, better bioavailability, and rapid intracellular uptake capability. PI and DAPI staining, cell cycle study by flow cytometry, DNA laddering, measurement of generation of reactive oxygen species using H2DCFDA stain, mitochondrial membrane potential by rhodamine 123 and Western blot analysis were performed to explore the pathways involved in the apoptosis. PLGA-DGN NPs showed cytotoxicity to MCF-7 and Ehrlich ascites carcinoma (EAC) cells without producing no toxicity to human and mouse lymphocytes. PLGA-DGN NPs induced apoptosis by elevating ROS, chromatin condensation, DNA fragmentation, cell cycle arrest, expression of proapoptotic proteins and mitochondrial dysfunction in MCF-7. The immunofluorescence studies of cytoskeletal and nuclear morphology revealed that after PLGA-DGN NPs treatment, the regular reorganization of actin filaments in MCF-7 cells became disrupted. In EAC-induced mouse solid tumor model, PLGA-DGN NPs significantly decreased cell proliferation, angiogenesis by reducing Ki-67 and CD-31 expression and the solid tumor were regressed and increased mean survival time of EAC-bearing mice was seen through the restoration of antioxidant status of the host mice. The findings confirm that PLGA-DGN NPs induced an antineoplastic effect that led to cell cycle arrest and apoptosis through the mitochondria-mediated intrinsic pathway and it is a promising anticancer nano-drug candidate for breast carcinoma.
Biography:
Ananya Pradhan is a PhD candidate in Department of Human Physiology in Vidyasagar University, Midnapore, West Bengal, India. She completed her BSc in Physiology (2007-2010) and MSc in Human Physiology (2010-2012) from Vidyasagar University. She joined Inspire fellowship, Dept of Science and Technology, Govt. of India, since 2014. Her research area is cancer nano-therapeutics and she has some good quality peer reviewed papers. Her special interest is to explore different mechanistic pathway of cancer therapeutics. She is a life member of Indian Science Congress Association and a member of Indian Association of Cancer Research.
Abstract:
Background: Gold nanoparticles have potential use in cancer diagnosis and therapy due to their size and enhanced permeability and retention effect that enables easy penetration and accumulation at tumor sites. Indole-3-carbinol (I3C), a phenolic phytochemical, has been reported to possess pro-apoptotic, anti-proliferative and anti-carcinogenic properties via modulation of immune pathways in Jurkat cell. So, an attempt has been made to green synthesize gold nanoparticles using indole-3-carbinol and to investigate whether its anticancer efficacy is enhanced at the nanoscale level or not by the induction of apoptosis.
Methodology: AuNPI3Cs were characterized and its cellular uptake was investigated using fluorescence microscopy. Induction of apoptosis of AuNPI3Cs in Jurkat and Dalton ascites lymphoma (DLA) cells was assessed by DAPI/PI staining, cell cycle study by flow cytometry, immunoblotting assay and by other relevant methods.
Findings: FTIR analysis confirmed the role of indole-3-carbinol in the stabilization of AuNPI3Cs. TEM analysis study revealed that AuNPI3Cs were mostly spherical in shape with an average particle size of 3nm. Results showed that the respective IC50 doses of AuNPI3Cs were significantly capable of elevating intracellular reactive oxygen species in Jurkat and DLA cells. AuNPI3Cs induced apoptosis by increasing reactive oxygen species, chromatin condensation, cell cycle arrest at G0/G1, expression of proapoptotic proteins and mitochondrial dysfunction in Jurkat cell, T cell leukemia and also in lymphoma cell. The fluorescence studies of cytoskeletal and nuclear morphology showed that AuNPI3Cs treatment changed the structural organization of actin filaments in T-cell leukemia cell.
Conclusion and Significance: The overall results firmly indicated that indole-3-carbinol, as appropriate reducing and stabilizing agent, led to the green synthesis of potent anticancer agent AuNPI3Cs with high potential for cancer therapy and may be considered as one of the best anticancer theranostic nanostructures among those reported until date.
Mohamed Zakaria Abdel-Rahman Sayer Dayer
Menoufia University, Egypt
Title: Prognostic factors for surgical outcome and survival in women treated for borderline ovarian tumors
Biography:
Mohamed Zakaria is currently working as a Assistant Lecturer of Gynecology & Obstetrics at Menoufia University. His Research Interest includes Ovarian tumors.
Abstract:
Data of 92 patients diagnosed with borderline ovarian tumors (BOTs) during the period from 2010 to 2017 in the National Cancer Institute (NCI), Cairo University, Egypt were retrospectively evaluated, Median follow up period was 42 months. The mean age at diagnosis was 42.7 yrs. Histopathology was serious in 63%, mucinous in 28.3%, and endometrioid in 3.3%. 65 patients (70.7%) had Stage IA disease, 17 patients had Stage IB disease (18.5%), 4 patients had Stage IC disease (4.3%), 2 patients had Stage II disease (2.2%) and 4 patients had Stage III disease (4.3%) at diagnosis. 49 patients (53.3%) underwent fertility-sparing surgery, of which 19 patients underwent Unilateral ovarian cystectomy, 5 patients underwent Bilateral ovarian cystectomy, 25 underwent Unilateral salpingo-oophorectomy. 43 patients (46.7%) underwent radical surgery including hysterectomy, bilateral salpingo-oophorectomy. 39 patients had micropapillary disease (42 %) and 2 patients had microinvasive disease (2.2%) on histopathology. 6 patients (6.5 %) had peritoneal implants of which 1 was invasive and 5 were non-invasive. The recurrence rate in the entire study group was 18.5%, 17.6% among patients underwent radical surgery and 82.4% among patients underwent fertility-sparing surgery. 12 of the recurrences (70.6%) were borderline whereas 5 were invasive (29.4%). Stages IA and IB had significantly higher disease-free survival than other stages. Patients with micro invasion had significantly lower free disease-free survival 10.5(9.52–11.5) vs 77.6(70.9 – 84.1). Radical surgery had significantly higher FDS than fertility-sparing surgery 75.8(70.2 – 81.4) vs 68.5(58.2 – 78.8).
Mohamed Zakaria Abdel-Rahman Sayer Dayer
Menoufia University, Egypt
Title: Prognostic factors for surgical outcome and survival in women treated for borderline ovarian tumors
Biography:
Mohamed Zakaria is currently working as a Assistant Lecturer of Gynecology & Obstetrics at Menoufia University. His Research Interest includes Ovarian tumors.
Abstract:
Data of 92 patients diagnosed with borderline ovarian tumors (BOTs) during the period from 2010 to 2017 in the National Cancer Institute (NCI), Cairo University, Egypt were retrospectively evaluated, Median follow up period was 42 months. The mean age at diagnosis was 42.7 yrs. Histopathology was serious in 63%, mucinous in 28.3%, and endometrioid in 3.3%. 65 patients (70.7%) had Stage IA disease, 17 patients had Stage IB disease (18.5%), 4 patients had Stage IC disease (4.3%), 2 patients had Stage II disease (2.2%) and 4 patients had Stage III disease (4.3%) at diagnosis. 49 patients (53.3%) underwent fertility-sparing surgery, of which 19 patients underwent Unilateral ovarian cystectomy, 5 patients underwent Bilateral ovarian cystectomy, 25 underwent Unilateral salpingo-oophorectomy. 43 patients (46.7%) underwent radical surgery including hysterectomy, bilateral salpingo-oophorectomy. 39 patients had micropapillary disease (42 %) and 2 patients had microinvasive disease (2.2%) on histopathology. 6 patients (6.5 %) had peritoneal implants of which 1 was invasive and 5 were non-invasive. The recurrence rate in the entire study group was 18.5%, 17.6% among patients underwent radical surgery and 82.4% among patients underwent fertility-sparing surgery. 12 of the recurrences (70.6%) were borderline whereas 5 were invasive (29.4%). Stages IA and IB had significantly higher disease-free survival than other stages. Patients with micro invasion had significantly lower free disease-free survival 10.5(9.52–11.5) vs 77.6(70.9 – 84.1). Radical surgery had significantly higher FDS than fertility-sparing surgery 75.8(70.2 – 81.4) vs 68.5(58.2 – 78.8).
Biography:
Katy French MD, BA University of Kansas 1996, MD Tulane University School of Medicine 2003, Anesthesia Residency Tulane University 2007, Cardiovascular Anesthesia Fellowship Texas Heart Institute 2008. Associate Professor of Anesthesiology and the Perioperative Medicine University of Texas MD Anderson Cancer Center 2008-current. Research and interests-maximizing efficiency in patient-driven perioperative anesthesia assessment, application of information technology to streamline clinical operations, and time-driven activity-based costing (TDABC) applied to the healthcare setting. Published and/or presented over 50 abstracts and peer-reviewed publications.
Abstract:
In 2017, an estimated 1,688,780 new cancer cases will be diagnosed. Many patients with a cancer diagnosis will need surgery as part of their treatment. The University of Texas MD Anderson Cancer Center saw 38,888 new patients in 2017 and performed over 20,000 operating room anesthetics. Advanced assessment of patients scheduled for operating room procedures helps reduce the percentage of cancellations that occur on the same day of the scheduled procedure. Same day surgery cancellations cause stress and frustration to all involved but most crucially for the patient and their family. The stress of the cancellation of a planned procedure has a negative impact on the perioperative patient experience. Our perioperative care process assesses all patients with planned OR procedures. All patients are screened using a 40 question triaging tool, embedded into our electronic health record and sent to our patients with the OR case is requested. All answers are validated with the patient by a clinical provider. Patients are then either seen in the clinic or called by phone prior to their planned procedure. 47% of our patients have a complex medical history as indicated by their triage questionnaires and seen in the clinic. Subspecialty consults are arranged as needed. The remaining 53% had less complex medical history and are assessed by phone. Our institution maintains a same day cancellation rate of 2.07%, assessing patients before their procedure date through direct contact with each patient by our providers. This contributes to positive patient experience in the perioperative period.
Meda-Monzón E
Hakken Enterprise S.A. de C.V., México
Title: GanplexTM and Kimera-TestTM: Biotechnological screening tools designed identify human cancer-related virus and SNPs in non-invasive samples
Biography:
Meda-Monzón E (MSc in Health Sciences), Biotechnology specialist, with a great passion for innovation. MSc Elizabeth has demonstrated ability to turn a promising concept into a world class product by implementing cutting edge technology. During the last four years, she has dedicated her talent and energy to the development of technologies for affordable in vitro diagnostics tools for HPV and cancer genetic propensity detection.
Abstract:
Most efforts of allopathic medicine are directed to treat diseases. This path has proved to be costly when chronic diseases, such as cancer and its associated viral co-morbidities, need to be treated and monitored in the long term. Hence, the development of prevention-oriented medicine may reduce the magnitude of the financial burden associated with practicing remedy-based medicine. GanplexTM and Kimera-TestTM, the prime products of Hakken Enterprise, were then conceived to identify individuals with high genetic risk of developing cancer before the disease becomes symptomatic. GanplexTM and Kimera-TestTM take advantage of DNA extracted from saliva and urine samples to identify cancer-related viruses and SNPs through multiplex assays in a single reaction. At current stage of development, both assays identify cancer related SNPs and the viral sequences with a sensitivity, specificity, and confidence higher than those reported for Sanger’s sequencing. Both assays require small DNA quantities to begin with and no purification of PCR products prior hybridization. This shortens to approximately 7 hours the time to provide a result. Hence, GanplexTM and Kimera-TestTM are biotechnological tools that provide the genetic information needed to identify individuals under risk of developing cancer, a circumstance that would help in personalizing cancer preventing protocols and introducing precision medicine into everyday’s life.
Samir Mehndiratta
Taipei Medical University, Taiwan
Title: Indole-3-ethylsulfamoylphenylacrylamides with Potent Anti-proliferative and Antiangiogenic Activities
Time : 16:15-17:15
Biography:
Samir Mehndiratta is a postdoctoral research fellow in Department of Medicinal Chemistry at Taipei Medical University (TMU), Taiwan. He has his expertise in small molecules as potent anticancer compounds and his work accentuates on designing and synthesizing inhibitors of various epigenetic modulations like HDAC inhibitors, HAT Inhibitors, target based therapy, designed multiple ligand (DML) based drug design and personalized medicines for the treatment of cancer. During his doctorate, he received QS-Apple Scholarship 2014 for outstanding research and social engagements. With high impact papers in various research journals he has been awarded with Outstanding Postdoctoral Award for year 2016 and 2017 from TMU and has also received Young Research Scientist Award 2018 from SBMLS (India).
Abstract:
Histone deacetylases (HDACs) display multifaceted functions by coordinating the interaction of signal pathways with chromatin structure remodeling and thus play an important role during malignancy progression. HDAC inhibition shows promise as a new strategy for cancer therapy and four HDAC inhibitors have been approved. We have synthesized a PXD101-LBH589 core model based series of potent indole-3-ethyl sulfomoylphenylacrylamides as potent inhibitors of HDACs, developed the SAR and evaluated them for their anti-cancer and anti-angiogenic effects.
Edyta Zyla
Jagiellonian University, Poland
Title: Flagellin mutant of Salmonella Typhimurium VNP20009 producing recombinant mouse PD-1 preserves the growth kinetics and mobility of the parental strain
Biography:
Edyta Zyla has been started her PhD studies at Jagiellonian University in Kraków. From the very first beggining of Bachelor studies she was gripped by Salmonella using in anticancer immunotherapy. She was chairing student project and currently she is beneficiary of project financed by Biophysics, Biochemistry and Biotechnology Department UJ. To expand her horizons she has started working in Protein Crystallography Laboratory.
Abstract:
The interaction of PD-L1 with T cell PD-1 receptor leads to the inactivation and death of T cells resulting in immunosuppression and undisturbed tumor development. We engineered Salmonella strain to deliver soluble PD-1 into tumor tissue. In principle, soluble PD-1 will compete with the PD-1 receptor on the T cell surface for binding to the PD-L1 ligand present on the surface of tumor cells and thus prevent T cell inactivation. The main goal of this work was to modify Salmonella therapeutic strain so it will be capable of efficiently secreting soluble PD-1 through the flagellar system. The flagellar system functions as a bacterial mobility motor but also serves as a secretory system for the extracellular elements of the flagellum. Special secretion signals direct certain proteins for flagellar channel-mediated secretion. To use the flagellar system for the secretion of recombinant proteins bacteria should be deprived of flagellin synthesis. To achieve this, we removed the fliC gene coding for flagellin monomer from the VNP20009 chromosome by homologous recombination and transformed the new strain with a plasmid coding for soluble PD-1 equipped with a suitable secretion signal. At present we are testing various secretion signals for optimal synthesis and secretion of PD-1 via the flagellar system. Interestingly, the characterization of the ΔfliC strain showed similarities characteristics to the parental one in terms of viability and growth kinetics. What is more, the mobility of the modified bacteria and the wild-type VNP20009 did not differ. However, the exposure of RAW264.7 cells to both Salmonella strains revealed that ΔfliC bacteria are less infective when compared to the parental strain. Nonetheless, in this case, the decreased cell infectivity might be beneficial as it will allow secreting PD-1 to the extracellular environment, where it may fulfill its anti-immunosuppressive task.
Anuja Konda
Mission San Jose High School, USA
Title: Pancreatic cancer awareness for better self-management
Biography:
Anuja Konda is passionate about biology, human anatomy, and disease detection and prevention. She is part of the Roberts Summer Academy Program 2018 at City of Hope National Medical Center focusing on research related to cancer and detection methodologies. She will be a senior at Mission San Jose High School in 2018-2019. She is shadowing physicians at Tri-City Health Center, and volunteering at Fremont Healthcare Center. She has certification in CPR. She has co-founded “All Against Alcohol and Drug Abuse” (AAADA.org) in 2016 for promoting awareness about Alcohol and Drug Abuse. AAADA has received recognition and commendation letters from the Congressman, Assembly members, and the Mayor.
Abstract:
Statement of the Problem: Pancreatic cancer has been reported as the fourth leading cause of cancer deaths in the United States. Due to the covert location of the pancreas in the human body, pancreatic cancer may go undetected until it progresses to an advanced stage. Pancreatic cancer starts in the pancreas and generally spreads to different parts of the body as it progresses. By the time the disease reaches the advanced stages, it can be fatal, and treatment or surgical resection may not be possible. Due to lack of awareness and obvious symptoms at an early stage, individuals seem to overlook the potential pancreatic cancer. The purpose of this study is to provide current information about pancreatic cancer, types of diagnosis, prominent cancer treatment facilities, and supportive resources for better self-management of disease.
Methodology & Theoretical Orientation: Among chronic diseases with high mortality rates, cancer is considered one of the most devastating diseases. In the normal process of the human body, cells continuously undergo division, death, and replacement by themselves in a controlled fashion. Cancer starts when cells are altered and uncontrollably divide without diminishing. The growth of abnormal cells in an uncontrolled fashion could spread cancer to different parts of the body, impacting the normal functionality of organs throughout the body. Some prevalent cancer diseases include lung & bronchus, colon & rectum, prostate, pancreas, breast, ovary, etc. In this research, a brief review and compilation of key information pertaining to pancreatic cancer are discussed along with historical data.
Conclusion & Significance: Due to the severity of pancreatic cancer, it is important that individuals be aware of the symptoms and signs of pancreatic cancer. With awareness, individual may be able to be proactive about the disease in its earlier stages so that the probability for successful long-term treatment may increase.