Day 2 :
Keynote Forum
Al Charest
Beth Israel Deaconess Medical Center Cancer Center, USA
Keynote: PDGFRα signaling strength confers sensitivity to vinblastine in glioblastoma
Biography:
Alain Charest, MSc, PhD is an Associate Professor in the Department of Medicine at Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. Dr. Charest received his postgraduate degrees at McGill University, Montreal, Canada. The focus of the Charest laboratory is on leveraging clinically relevant genetically engineered mouse models of primary malignant brain cancer to study central aspects of gliomagenesis and molecular responses to therapeutic interventions. Recent work from the Charest lab involves studies on how PDGFRa signaling strength confers sensitivity to chemotherapeutic agents in Glioblastoma Multiforme.
Abstract:
The PDGF Receptor alpha is overexpressed and activated in a substantial number of Glioblastoma (GBM) tumors. Although the activation of PDGFRα in GBM is chronic in nature, our knowledge of PDGFR signaling pathways is largely derived from acute stimulation studies, which are less representative of the clinical setting. In order to decipher the identity and clinical significance of sustained PDGFRα signaling during tumorigenesis and to reveal therapeutic vulnerabilities, we created a novel genetically engineered conditional mouse model based on genomic events that are observed in patients, that is the overexpression of PDGFRα and its chronic activation by PDGF-A ligand in the context of loss of function of the p53 tumor suppressor gene. To broaden its clinical relevance, we created our model system with a titratable expression of PDGF-A, which is specific for PDGFRα homodimers. De novo intracranial PDGF-A;PDGFRα tumors arise in these mice with full penetrance and short latency and display histological and molecular features that are consistent with Proneural GBMs. Tumor growth in animals was intimately related to the levels of PDGF-A ligand expression, suggesting differences in cellular signaling in tumors with low and high levels of activated receptors. Indeed, global phospho- (pTyr, pSer/pThr) and total proteomic analyses on cells derived from PDGFRα-positive GBMs revealed that the strength and utilization of specific signaling pathways are dependent on the levels of PDGFRα activation. Further investigation of these pathways unveiled a role for the microtubule binding protein Stathmin 1 (STMN1) in the vulnerability of these GBM cells to the microtubule-disrupting drug vinblastine. Our results open the possibility that GBM patients whose tumors express active PDGFRα could benefit from treatments with vinca alkaloid type of therapeutic agents. Our observations also argue strongly for the development of inhibitors of STMN1 function for the treatment of PDGFRα positive GBMs.
Keynote Forum
Jianyu Rao
David Geffen School of Medicine-UCLA, USA
Keynote: Nanocytology as a novel biomarker for cancer
Biography:
JianYu Rao is an Professor of Pathology and epidemiology, Chief of Cytopathology and Director of Gynecological Pathology. He is a surgical pathologist and cytopathologist specialized in genitourinary tract and gynecological pathology. He is also a molecular epidemiologist and cancer cell biologist. He did his training of Anatomic and Clinical pathology as well as Cytopathlogy here at UCLA from 1994 to 1999. He became the faculty at Department of Pathology and Lab Med since 1999.
Abstract:
The hallmark of cancer is the invasive and metastatic nature of the disease. Cancer cell invasion and metastasis are partly regulated by altered cytoskeletal structures that result from the complex interplay of activation/inactivation of multiple signaling pathways regulating these cellular events, which can occur at either the genetic or epigenetic level. Thus, attempts to accurately assess these physiologically relevant mechanical properties of cancer cells using single, or even multiple marker profiles at the DNA, RNA, or protein level, may not be effective. Recently, we showed that cancer cell mechanical properties, or mechanotypic biomarkers, including cell elasticity and deformability can be directly and accurately measured by state of the art, label-free technologies at the single cell level. These mechanical properties of cells can be a marker for cancer cell behavior including invasion, metastasis and drug response. We developed an approach that uses mechanotypic profiling to complement morphological and molecular analyses, a process called “Nanocytology” which collectively enable robust and high throughput measurements and can potentially be implemented even in resources poor areas. The nanocytology approach combined with targeted delivery of nanoparticles with molecular-tailored anti-cancer agents may provide a more effective alternative for cancer detection and management.
Keynote Forum
Andrea Nicolini
University of Pisa, Italy
Keynote: Immunotherapy in endocrine dependent metastatic breast cancer
Biography:
Nicolini graduated (summa cum laude) at School of Medicine, University of Pisa in 1974. He received postgraduate diplomas at University of Pisa in Internal Medicine (1980), Pneumology (1984), and Nuclear Medicine (1986). His research interests include breast and gastrointestinal cancer and their metastases, tumour markers, post-operative follow-up, physiopathology, immunology and immunotherapy of cancer, and thyroid tumours.
Abstract:
Hormone therapy is advised for ER+ metastatic breast cancer patients due to its efficacy concomitant with low toxicity; however, in most patients the occurrence of resistance is a not well yet understood hurdle to overcome. In these patients, during clinical benefit (CB) from conventional anti-estrogens, the addition of cycles of sequential immunotherapy could prolong the benefit and delay the arising of acquired hormone resistance. In order to validate this hypothesis, in 1992 we started an open exploratory clinical trial. Forty-two (42) of these patients in CB during first line anti-estrogen salvage therapy also received beta-interferon (INF-beta) 3,000,000 IU i.m./day 3 days/week, weeks 1-4 and successively recombinant interleukin-2 (IL-2) 3,000,000 IU s.c./day 3 days/week, weeks 5-8 until progression. The immunotherapy cycle lasted 10 weeks and the patient continued anti-estrogen alone during weeks 9-10, the 11th week being the first week of the successive cycle. At each control visit, routine laboratory examinations and serum measurement of a CEA-TPA-CA15.3 tumor marker (TM) panel were carried out, and an immunological assessment was made (total lymphocytes, CD4+, CD8+, NK cells, T-reg, IL-6, IL-10, IL-12, TNFa, TGFbeta1 and IFN-gamma.). The addition of INF-beta-IL-2 sequence significantly prolonged clinical benefit and overall survival from conventional anti-estrogens. During CB as opposed to progression, a significant immune stimulation was observed. During CB also a significant CEA, TPA, CA15.3 decrease occurred 24–72 h after interleukin-2 administration. At the progression a significant increase for CEA and for all 3 markers (standardized values) was found 24–72 h after interleukin-2 administration. In patients who survived less than 5 years, the Treg cell increase occurred at a significantly shorter time interval than in those who survived longer than 5 years (20 vs. 45.5 months, respectively; P=0.001). To further confirm these promising results, a multicenter prospective phase II trial is going to be launched by the Cancer Center Institute of Tuscany in Italy.
- Anti-Cancer Drugs and Delivery | Biomarkers | Novel Approaches to Cancer Therapeutics | Chemotherapy | Cancer and Lifestyle Connection | Cancer Biomarkers | Cancer Cell Biology, Diagnosis and Applied Research
Session Introduction
Xiequn Xu
Peking Union Medical College Hospital, China
Title: Preoperative neutrophil to lymphocyte ratio predicts central compartment lymph nodes metastasis in papillary thyroid microcarcinoma
Time : 11:50-12:15
Biography:
Xiequn Xu has completed his MD at the age of 27 years from Peking Union Medical College Hospital. He is the associate professer of general surgery in Peking Union Medical College Hospital, a ranked No 1 hospital in China. He has published more than 30 papers in reputed journals.
Abstract:
Abstract
Background:The incidence of papillary thyroid microcarcinoma (PTMC) is rising in most countries, which is a consequence of efficacy earlier diagnosis. Even though the central lymph nodes metastasis has be considered to be a risk factor of poor prognosis in PTMC, there is no reliable preoperative assessment for it. Our study was to confirm the value of preoperative neutrophil to lymphocyte ratio (NLR) to predict the central lymph nodes metastasis of PTMC by retrospective case control study.
Methods: A total of 142 patients who underwent total thyroidectomy with prophylactic central lymph nodes dissection at a single institution between Oct 2013 and Jan 2015 were analyzed. Patients were categorized into central lymph node metastasis positive and negative, those were confirmed by histological. Age, gender, blood cells counts with differential counts, medical history were measured or recorded in each patient before operation.
Results: In our study, 37.14% (n=52) were CLN metastasis positive while 62.86% (n=88) were negative. The factors that correlated (P<0.05) with the presence of central lymph node metastases were age and NLR. The NLR were significantly higher in the Central lymph node negative group (p=0.027). The optimum NLR cut-off value obtained from ROC analysis was 2.32 (Sensitivity 44% and Specificity 87.1%). The optimum Age cut-off value obtained from ROC analysis was 45(Sensitivity 53.1% and Specificity 76.3%).
Conclusions: Higher preoperative NLR could be a reliable negative marker for central compartment lymph node metastasis and cut-off value of 2.32 be supposed.
Madhura Satish Bhave
Nanyang Technological University, Singapore
Title: Inhibitive effect of Non-viable derivatives of Clostridium sporogenes on colorectal cancer cells
Time : 12:15-12:40
Biography:
Biography
Madhura is currently pursuing her PhD at Nanyang Technological University (NTU), Singapore. She completed her Bachelor of Engineering in Bioengineering from NTU where her final year honours thesis was on the subject of Bacterial Cancer Therapy. She was on the Dean’s List for the academic year of 2014/2015. Her work has been published in the Scientific Reports journal, by the Nature Publishing Group.
Abstract:
Abstract
Traditional cancer treatments like chemotherapy and radiation therapy continue to have limited efficacy due to phenomena like tumor hypoxia and multi-drug resistance. Bacterial cancer therapy has the potential to overcome these problems, through the use of anaerobic spores of bacteria such as the proteolytic Clostridium sporogenes. However, the use of spores or live bacteria comes with the risk of toxicity and infection. To circumvent these issues, the anti-cancer effect of heat-inactivated C. sporogenes bacteria (IB) and its secreted bacterial proteins, known as conditioned media (CM) was investigated. These non-viable bacterial derivatives were administered to CT26 and HCT116 colorectal cancer cells in a 2-Dimensional (2D) and a 3-Dimensional (3D) platform. IB significantly inhibited cell proliferation of CT26 in a dose-dependent manner to 6.3% of the control in 72 hours for the 2D monolayer culture. In the 3D spheroid culture, cell proliferation of HCT116 spheroids notably dropped to 26.2%. Similarly the CM also remarkably reduced the cell-proliferation of the CT26 cells to 2.4% and 20% in the 2D and 3D models, respectively. Results suggest that physical interaction between the IB and the cancer cells lead to their inhibition, while the secreted proteins present in CM were responsible for anti-cancer effect observed. The bacterial derivatives exhibited strong inhibitive effects on colorectal cancer cells, indicating that there is a safer alternative to the use of spores and live bacteria. With further research, these non-viable derivatives could be developed as an alternative or adjunct to traditional cancer treatments.
Magdalena Kodura
Karolinska Institute, Sweden
Title: Breast carcinoma metastasis suppressor gene 1 (BRMS1): Update on its role as the suppressor of cancer metastases in the context of combinatorial cancer treatment
Time : 12:40-13:05
Biography:
Biography
Two Master of Science degrees (Medical Physics, AGH, Krakow, Polen and Molecular Biotechnology, KTH, Stockholm, Sweden). Both of my theses were performed and defended with highest grades at Karolinska Institute in Stockholm, Sweden. The results of my Master of Science thesis in Molecular Biotechnology turned out to be so interesting that I had a pleasure to present them at Personalized Cancer Care Symposium in Oslo (Norway) in 2012. My supervisor at Karolinska Institute, Serhiy Souchelnytskiy, saw so much scientific potential in me during my work at his lab that he invited me to write a review which was published in Cancer and Metastasis Reviews Journal and which was met with a worldwide interest and many invitations to conferences. The findings of my review as well as my own personal experimental results are so interesting and crucial for the development of combinatorial cancer treatment that I hope I will have a pleasure to present them at your esteemed congress in Philadelphia in December and inspire a positive development in combinatorial cancer therapy.
Abstract:
Abstract
Background: BRMS1 (Breast Cancer Metastasis Suppressor-1) protein was discovered over a decade ago as a potential tumor suppressor gene. Our review summarizes the recent findings about the structure of BRMS1, mechanisms of its action and the role of BRMS1 in the cancer progression. In addition, I would like to discuss the BRMS1 findings in a broader context. Combinatorial treatment of breast cancer with the joined forces of chemotherapy, adjuvant therapy, cytotoxic agents and radiation has had a great impact on the prolonged survival of breast cancer patients. Metastasis remains however the major reason behind the mortality rate in this group of patients and as such requires more attention in understanding the potential influence of other parallel pharmaceutical treatments.
Objectives: The aim of my presentation will be to summarize the recent findings regarding the effect of BRMS1 protein on the suppression of cancer metastasis as well as to explore the correlation between the activity of BRMS1 protein, growth factors (TGF-β and EGF), antidepressants (fluoxetine and amitriptyline) and the stimulation of cell survival and migration of breast cancer.cells in a combinatorial cancer treatment.
Results: As a suppressor of metastasis, BRMS1 has demonstrated a variety of ways to act on the cell functions, such as cell migration, invasiveness, angiogenesis, cell survival, cytoskeleton rearrangements, cell adhesion, and immune recognition. This variety of effects is a likely reason behind the robustness of anti-metastatic influence of BRMS1. Intracellular signaling mechanisms employed by BRMS1 include regulation of transcription, EGF/HER2 signaling, and expression of NF-kB, fascin, osteopontin, and IL-6. Recently reported clinical studies confirm that BRMS1 can indeed be used as a prognostic marker. Approaches to employ BRMS1 in a development of anti-cancer treatment have also been made. The combinatorial influence of growth factors and antidepressants showed a dynamic modulation depending 2 on the presence of BRMS1 protein. It indicates the existence of a correlation between BRMS1, TGF-β, EGF, fluoxetine and amitriptyline. Furthermore, the effect of antidepressants differed depending on the kind of parallel treatments and therefore underlined the significance of drug-drug interactions. Antidepressant amitriptyline strongly promoted colony formation in MDA-MB-231-pMEP4 cell line, which was observed in both membrane migration assay and clonogenic assay. The same treatment resulted in a complete inhibition for MDA-MB-231-pMEP-BRMS1 cell line. Although the study requires to be confirmed by larger number of experiments, it may suggest that breast cancer patients taking amitriptyline (while not expressing BRMS1 protein) are exposed to increased risk of metastasis. On the other hand, for breast cancer patients who express BRMS1 protein and are treated with amitriptyline, it may imply an outstanding inhibiting effect of amitrypryline treatment on metastasis. Moreover, BRMS1 proved to have an impact on fluoxetine activity by inhibiting the stimulating effect of fluoxetine on the treatments with TGF-β, which were earlier observed in MDA-MB-231-pMEP4 cell line. In contact inhibition assay the stimulation of senescent cells by BRMS1 may suggest the role of BRMS1 in the inhibition of uncontrolled cancer.cell.proliferation. Conclusions: The studies reviewed here with respect to BRMS1 structure, cellular effects, intracellular signaling, and clinical value consolidate the importance of BRMS1 in the development of metastasis. In addition, the results of our study imply a significant correlation between BRMS1 protein, growth factors and antidepressants. A strong, opposite impact of amitriptyline on colony formation in both BRMS1- expressing and non-expressing cell lines requires a further investigation of the mechanism of interactions between BRMS1 and the treatment agents used in the study. It is advised in order to improve the outcome of the cancer treatment as well as the cancer related depression treatment. Furthermore, the results indicate that the future cancer treatment needs to consider not only drug-drug interactions but also a cross-talk between the drugs and the proteins involved in the cell growth and metastasis.
Chinedu S Aruah
National Hospital Abuja, Nigeria
Title: Anaemia in cancer patients undergoing radiotherapy and chemotherapy in National Hospital Abuja, Nigeria
Time : 13:50-14:15
Biography:
Abstract:
Introduction: Many cancer patients present with anaemia prior to radiotherapy and chemotherapy or may experience anaemia /worsening of anaemia at some point during treatment.
Aims and Objectives: The aim of the study was impact of anaemia in cancer patients undergoing Radiotherapy and Chemotherapy.
Methodology: 201 cancer patients of both sexes with histopathologically confirmed malignancies (solid cancers). Patient’s pre-treatment Hb was taken. Patients were distributed into Radiotherapy, Chemotherapy and Chemoradiation. Their Hb were measured once every 2 weeks. The blood film pictures of the patients were examined. The whole process was terminated after 3 consecutive Hb reading or after week 6. Anaemia was classified into:
Less than 10g/dl - Severe anaemia
10 - 10.9g/dl - moderate anaemia
11 - 12 g/dl - mild anaemia
12 g/dl and above - no anaemia.
Results and Analysis: Out of 201 cancer patients, 86.1% were female and 13.9% were male. Age range, 25 - 75 years, 100 patients were on Chemotherapy, 63 patients on Radiotherapy and 38 patients on Chemoradiation. The prevalence in anaemia in cancer patients undergoing radiotherapy and chemotherapy was found to be 63% as shown by blood film picture (i.e average of 72%, 42.9% and 73.7%).
At the end of therapy, 62% (100) patients on Chemotherapy and 55.6% (63) patients on Radiotherapy had their Hb level between 11-12g/dl, 39.5% (38) cancer patients on Chemoradiation arm had Hb value of 10-10.9 g/dl. At P- value > 0.05, there was no statistical significance on distribution of mean Hb, standard deviation based on sex and treatment type.
Conclusion: Prevalence of anaemia in the study group was found to be 63% while 37% had adequate haemoglobin (Hb) after the therapy as reflected in the blood film picture. At 95% confidence interval, Chemotherapy had greatest impact on Hb level during therapy. Thus Chemotherapy; 9.60-10.62g/dl, Radiotherapy; 11.52-12.1 3g/dl, Chemoradiation therapy; 10.98-11.3 6gIdl.
Walied A Kamel
Keio University, Japan
Title: Simvastatin induces apoptosis of Osteosarcoma cells: A novel potential therapeutic approach
Time : 14:15-14:40
Biography:
Walied kamel, 32 years old, a PHD student at keio unviersity, school of medicine, Tokyo, Japan.
Abstract:
Osteosarcoma (OS) is the most common, non-hematopoietic, primary malignant bone tumor. Previously, we developed an OS mouse model by overexpressing c-MYC in bone marrow stromal cells derived from Ink4a/Arf knockout mice. We isolated highly tumorigenic cells (designated AXT cells) from tumors after serial transplantation. To obtain the novel candidate agents for OS, we performed drug screening and found that statins strongly suppressed AXT cell growth.
Simvastatin treatment inhibited cell proliferation and induced apoptosis, which was almost fully rescued by the supplement of mevalonate and geranylgeranyl pyrophosphate but modestly by farnesyl pyrophosphate, suggesting that protein geranylgeranylation has a greater impact on OS cell viability.
Simvastatin treatment inactivated RhoA through translocation of RhoA from membrane to cytosol and RhoA-GTP was accumulated by disruption of the interaction between RhoA and Rho-GDI.
As a downstream signaling of RhoA, AMPK-p38MAPK pathway was strongly activated by simvastatin treatment, with AMPK functioning as an upstream effector of p38MAPK. Inhibition of AMPK or p38MAPK activation rescued apoptosis induced by simvastatin treatment, indicating that simvastatin exerts antitumor activity in OS via activation of AMPK- p38 MAPK pathway.
Although treatment with simvastatin alone did not inhibit OS tumor growth in vivo, its combination with a fat-free diet induced a significant antitumor effect that was further enhanced by metformin administration. These findings suggest that the activation of AMPK- p38 MAPK pathway by statins become a potential therapeutic option for OS.
Angela Katrina G Fonte
Far Eastern University, Philippines
Title: Decision-making of cancer patients about End-of-Life: The lived experience
Time : 14:40-15:05
Biography:
Angela Katrina G. Fonte is a Philippine Registered Nurse. She completed Bachelor of Science in Nursing at the Far Eastern University Manila, in the year 2010 and earned Master of Arts in Nursing Major in Medical-Surgical, year 2015 at the same university. As a passionate and dedicated registered nurse, she practice critical care nursing for more than two years at Marikina Valley Medical Center and later joined Asian Hospital and Medical Center in their Medical-Surgical Intensive Care Unit. She is a Fellow of the Royal Institute of Nurses, Singapore.
Abstract:
Understanding the perception of an end-stage cancer patient about end-of-life decision making can help the patient’s relatives, healthcare providers, and the person himself or herself in attaining the best quality of life in their exit event. The aim of this study is to deeply gain an understanding of the voice and feelings of stage 4 cancer patients in making decisions for end-of-life. The study was conducted using a qualitative phenomenological approach. Five participants who are of sound mind and able to make rational decisions shared their preferences. The participants were selected using a non-probability, criterion, purposive sampling. Data were gathered through the use of a semi-structred interview. Four major themes emerged from the analysis of the data. The themes were leaving protracted misery, divesting the burden, feeling of complacency and living in a former time.
These themes encircles mainly on the issue of cycle of suffering anf prolonging one’s agony with the use of life-saving measures which can reduce the quality of life. Findings of the study revealed that end-of-life deision making is encapsulated with different factors which include physical discomfort and exhaustion, emotional distress, spiritual dilemma and financial burden. Recommendations include educational training for nurses about end-of-life care and discussion of ethical issues, culturally competent care, and management of patients who are facing end-of-life decision making. It is also recommended that physicians should take the lead and explore the end-of-life preferences of patients and their families.
Cheng Chin Kuo
National Health Research Institutes, Taiwan
Title: Endothelium-derived 5-Methoxytryptophan acts as a therapeutic biomarker for systemic inflammation
Time : 15:05-15:30
Biography:
Dr. Cheng-Chin Kuo has completed his PhD at the age of 30 years from National Defense Medical Center, Taipei, Taiwan and postdoctoral studies from Academia Sinica, Taipei. In 2007, he joined the National Health Research Institutes as Assistant Investigator. In 2013, he got promotion to Associate Investigator. He has published more than 34 papers in reputed journals and has been serving as an journal reviewer. His current researches are to use comparative metabolomics analysis coupled with cellular biochemical approaches and animal model to determine physiological relevance and pathophysiological connection between physiological metabolites and inflammatory diseases such as systemic inflammation, vascular diseases, and cancer.
Abstract:
Systemic inflammation has emerged as a key pathophysiological process which induces multi-organ injury and causes serious human diseases. Endothelium plays a critical role in maintaining cellular and inflammatory homeostasis, systemic inflammation and progression of inflammatory diseases. We postulated that endothelium produces and releases endogenous soluble factors to modulate inflammatory responses and protect against systemic inflammation. We found that conditioned medium (CM) of endothelial cell (EC) inhibited cyclooxgenase-2 (COX-2) and interleukin-6 expression in macrophages stimulated with lipopolysaccharide (LPS). Analysis of CM extracts by liquid chromatography–mass spectrometry (LC-MS) showed the presence of 5-methoxytryptophan (5-MTP) but no other related tryptophan metabolites. Furthermore, endothelial cells-derived 5-MTP suppressed LPS-induced inflammatory responses and signaling in macrophages and endotoxemic lung tissues. LPS suppressed 5-MTP level in EC-CM and reduced serum 5-MTP level in the murine sepsis model. Intraperitoneal injection of 5-MTP restored serum 5-MTP accompanied by inhibition of LPS-induced endothelial leakage and suppression of LPS- or cecal ligation and puncture (CLP)-mediated pro-inflammatory mediators overexpression. 5-MTP administration rescued lungs from LPS-induced damages and prevented sepsis-related mortality. Importantly, a considerable amount of 5-MTP was detected in healthy subjects (1.05±0.39 ïM) while 5-MTP level in septic patients (0.37±0.15 ïM, p<0.0001) was significantly reduced in septic patients. We conclude that 5-MTP belongs to a novel class of endothelium-derived protective molecules which defend against endothelial barrier dysfunction and excessive systemic inflammatory responses. Being an endogenously produced compound, 5-MTP has the advantage of having less unexpected adverse effects. Thus, 5-MTP will be a valuable lead compound for new inflammatory drug development. Another potential clinical application of 5-MTP is its use as a biomarker of sepsis and other systemic inflammatory disorders. Hence, it may be useful as a “Therapeutic” biomarker for selecting sepsis patients for 5-MTP therapy.
Olufemi David Akilo
University of the Witwatersrand, South Africa
Title: An in vitro evaluation of carmustine-loaded Nano-co-Plex for potential magnetically targeted intranasal delivery to the brain for brain tumor management
Time : 15:50-16:15
Biography:
Olufemi David Akilo has just completed his PhD in Pharmaceutics specializing in drug delivery systems at the Department of Pharmacy and Pharmacology, University of the Witwatersrand, Johnnesburg South Africa. He currently works with Faculty of Health Sciences, University of the Witwatersrand University. He has authored a book chapter, research paper in a reputed journal and has filed a patent with South Africa patent Agency. He has also presented papers in several local and international conferences.
Abstract:
The aim of this work was to synthesize polyvinyl alcohol/polyethyleneimine/folate (Polyplex) complex coated Magnetite (Nano-co-Plex) with superparamagnetic capability and targeting attributes loaded with carmustine (BCNU) for potential magnetically targeted delivery of BCNU to the brain following intranasal administration for brain tumor management. This was achieved by co-precipitation reaction of Fe2+ and Fe3+ at high pH under N2, epoxidation of PVA and EDC/NHS coupling reaction of Folate with PEI. Drug loading was carried out in the dark. The release study was carried out by dispersing the dried BCNU-Nano-co-Plex in PBS pH 7.4 at 37°C. The formulation was characterized employing Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric Analysis (TGA), Transmission Electron Microscope (TEM), Zetasizer, Superconducting quantum interference device (SQUID) and X-ray Diffraction (XRD) techniques. FTIR spectra confirmed the synthesis of BCNU-loaded Polyplex coated Magnetite. The morphology, size and stability of the formulation showed hexagonally shaped particles with average size of 45nm with zeta potential of +21mV and poly dispersity index (PDI) of 0.22. XRD results further confirmed the crystalline nature of the formulation. The thermal analysis indicated that 1/3 of the total weight of the formulation constituted the drug-loaded polymeric coating. The magnetic studies showed superparamagnetic attribute of the formulation with high magnetization value. The loading capacity of the synthesized Nano-co-Plex was efficient for BCNU. The release profiles indicated a sustainable release of BCNU, with up to 75% of drug released after 72 hours. BCNU-loaded Nano-co-Plex was synthesized successfully.
Noor Mohammed
Birmingham, UK
Title: How many cell death pathways that Doxorubicin can affect HepG2 cells?
Time : 16:15-16:40
Biography:
Abstract:
Doxorubicin (DOX) is a potent antibiotic anti-cancer drug that is used either in isolation or in combination, for treating ovary, haematological, breast, stomach, liver, and prostate cancers. This drug has the ability to damage DNA and inhibit macromolecules (DNA and RNA) by producing free-radicals. Several studies have shown that Dox induces P53 activation leading to apoptosis in both normal and tumour cells, by causing cytochrome c release from the mitochondria which ultimately leads to apoptosis via caspase 3. We have investigated the molecular mechanisms of DOX induced hepatic cell death. This study shows that DOX can induce cell death in HepG2 cells through two different mechanisms. The use of caspase substrates and caspase inhibitors confirm that apoptosis through caspase 9 and caspase 3 are involved. Using HepG2 cells transfected with LC3-GFP, it was also noted that a high percentage of LC3-GFP punta were seen using fluorescence microscopy, following DOX treatment, which suggests that autophagy is also involved. However, lactate dehydrogenase release assays and the use of necrostatin, on DOX treated cells indicate that necrosis is unlikely to be involved.
Vagner Rodrigues Santos
Universidade Federal de Minas Gerais, Brazil
Title: Protection against oral mucositis in patients undergoing radiotherapy of the head and neck with topical mucoadhesive gel containing propolis
Time : 16:40-17:05
Biography:
Vagner Rodrigues Santos is Graduate in Dentistry, Associate Professor at School of Dentistry of the Minas Gerais Federal University(SD/UFMG). He has PhD in Oral Pathology (Faculty of Medicine/UFMG), Master in Microbiology(INRA–France), and Post-doctor in Natural Products at University of California Berkeley, USA. He is coordinator of Dentistry Care Clinic to Irradiated in head and neck Patients. Participates in the post-graduate program , guides doctoral, master's and undergraduate research students. Search developing new drugs based on propolis and medicinal plants for prevention and treatment of oral lesions. He has 50 published papers with 387 citations by ResearchGate.
Abstract:
The objective of this phase II study was to determine the effectiveness of a mucoadhesive propolis gel in the prevention of radiation-induced oral mucositis. Thirty-four patients who were selected to undergo radiation therapy for oral cancer were included in this open-label trial. They were advised to use a mucoadhesive gel containing propolis 5,0% w/v three times a day starting one day before the course of radiation therapy and concluding after 2 weeks of radiation therapy. A weekly follow-up for evaluation of food intake, pain and grading of mucositis was performed. In order to confirm the absence of Candida-related mucositis in patients who developed mucositis, it was performed exfoliative cytology of buccal mucosa, palate and tongue and the material for Candifast(®) Candida species identification. At the end of the study was made the compliance of patients, quality, appreciation and acceptance of product evaluation. Twenty patients did not develop mucositis, two patients developed grade 1 mucositis and two patients developed grade 2 mucositis. None of the patients discontinued food intake and no pain was observed during the study. Candidosis was not detected in any patient. Mucoadhesive propolis gel could be considered as a potential topical medication for preventing radiation-induced oral mucositis. Acnowledgements:FAPEMIG/CNPq/ CENEX-FOUFMG/PROEX-UFMG.