- University of Miami, USA
- Title:Carbon Dots as Versatile Drug Nanocarriers in Modern Medicine
- Time :
Carbon dots (CDs) with size less than 10 nm have recently triggered great attention in the research of material science and biomedical engineering due to their unique properties such as small size, excellent photoluminescence (PL), high water-dispersity, biocompatibility, nontoxicity and abundant surface functionalities. In this presentation, I will firstly introduce diverse preparations of CDs. Extensive structural characterizations have been used to hypothesize comprehensive structural models for 3 distinct CD species that represent both top-down and bottom-up approaches in order to optimize their properties and applications
Then, I will mainly focus on many excellent biomedical applications of the CDs recently developed in our lab: (1), in vivo experiment suggested that glucose-based CDs could cross the blood-brain barrier (BBB) due to the presence of glucose transporter proteins on the BBB; (2), a drug delivery system of carbon nitride dots conjugated with an anti-cancer therapeutic drug and a targeting molecule was capable of effective treatment against diffuse large B-cell lymphoma both in vitro and in vivo revealing efficient therapeutic capabilities with minimal toxic side effects; (3), metformin-derived CDs showed a unique nucleus targeting property, which suggests a huge potential for future nucleus-targeting drug delivery; (4), CDs have constantly shown the capability to inhibit the formation of amyloid precursor protein (APP), beta-amyloid (Aβ) and Aβ fibrils. CDs are promising nanomedicine and drug nanocarriers to treat Alzheimer’s disease (AD); (5) a pilot study showed a versatile nanocarrier could be assembled via the direct conjugation between distinct CDs to fulfill multitasks.
Dr. Roger M. Leblanc received his B. S. in chemistry in 1964 from Université Laval, Canada, and Ph. D. in physical chemistry in1968 from the same university. He was appointed as professor in 1994 and chair of Department of Chemistry at University of Miami from 1994 to 2002 and again from 2013 to present. He was also one of the three editors of Colloids and Surfaces B: Biointerfaces from 1998 to 2013. He has published 520 scientific articles in peer-reviewed journals. As a professor, he has supervised more than 100 M.S. and Ph.D. students.
- General University Hospital of Ciudad Real, Spain
- Title:Prophylaxis of Venous Thromboembolic Disease in Cancer Patients.
- Time :
Thrombotic risk should be evaluated regularly in different clinical settings of cancer patients. Thromboprophylaxis with low molecular weight heparin (LMWH), being able to be complemented with mechanical means, or the alternative use of a inferior vein cave filter (FVCI) in the case of PE or acute proximal DVT of IBD, facing procedures that are contraindicated for anticoagulation, maintaining a certain thromboprophylaxis level, above other anticoagulants, is recommended for the majority of hospitalized cancer patients, although the safety of primary thromboprophylaxis in this context is unknown. Routine thromboprophylaxis in outpatients receiving chemotherapy is not recommended, except in outpatients who have other factors that condition high thrombosis, and thromboprophylaxis can be offered with apixaban, rivaroxaban, or low molecular weight heparin (LMWH) as long as there are no factors. risk factors for bleeding and without drug interactions. In patients who are going to undergo oncological surgery, thromboprophylaxis should start before surgery and continue for a minimum of 7 to 10 days, and in cases of major surgery, up to 4 weeks. Routine thromboprophylaxis in prevention of MMSS thrombosis in patients with central venous catheters (CVCs) is not recommended.
Graduate of Medicine and Surgery in 1979, Autonomous University of Barcelona (UAB). Vall D´hebrón Teaching Unit. Bachelor of Medicine, UAB, in 1979
Internal Medicine Specialist, via MIR, 1984.
Sufficiency Research Diploma, University of Alcalá.
Doctor from the University of Alcalá, with Outstanding Cum Laude unanimous qualification.
Diploma from the UNED on Probability and Statistics in Medicine.
Diploma in Pedagogical Aptitude, C. Real School.
Postgraduate Diploma in Venous Thromboembolic Disease, 30 credits from the European Credit Trnasfer System, equivalent 750 hours, accredited by the Autonomous University of Barcelon (Fundación Doctor Robert)
-MASTER IN GETIÓN CLINICAL UNITS (University of Murcia), through the Spanish Society of Internal Medicine, Spanish Society of Respiratory Pathology, Spanish Society of Cardiology.- Official tutor of postgraduate training in Internal Medicine.
Head of Section of Internal Medicine from 1992 to 2005.
- National Cancer Institute/NIH, USA
- Title:The Landscape of Genomic Copy Number Alterations in Carcinomas and their Consequences on Gene Expression Levels and Disease Outcome
- Time :
Aneuploidy, the unbalanced state of the chromosome content, represents a hallmark of most solid tumors. Such aneuploidies result in tumor specific genomic imbalances, which emerge in premalignant precursor lesions. Moreover, increasing levels of chromosomal instability have been observed in adenocarcinomas and are maintained in distant metastases. A number of studies have systematically integrated copy number alterations with gene expression changes in primary carcinomas, cell lines, and experimental models of aneuploidy. In fact, chromosomal aneuploidies target a number of genes conferring a selective advantage for the metabolism of the cancer cell. Copy number alterations not only have a positive correlation with expression changes of the majority of genes on the altered genomic segment, but also have effects on the transcriptional levels of genes genome-wide. Finally, copy number alterations have been associated with disease outcome; nevertheless, the translational applicability in clinical practice requires further studies. Here we review (i) the spectrum of genetic alterations that lead to solid tumors, (ii) the most frequent copy number alterations at different stages of cancer, (iii) exemplify their positive correlation with gene expression levels, and (iv) discuss copy number alterations that are potentially involved in disease outcome of individual patients.
Dr. Ried received his M.D. from the Max Planck Institute for Medical Research in Heidelberg, Germany. After having completed his postdoctoral training at the University of Leiden and at Yale University, he joined the faculty of the National Human Genome Research Institute in 1994. Dr. Ried became an investigator at the NCI in 1998 and a senior investigator and Chief of the Cancer Genomic Section in 2002. Since 1998 he has co-directed the Cancer Chromosome Aberration Project. In 2000, Dr. Ried received the AMGEN award of the American Society of Biochemistry and Molecular Biology. Dr. Ried serves as a member of the editorial board for numerous scientific journals.
- University of Texas ,USA
- Title:Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis.
- Time :
Dr. Russel J. Reiter is Professor of Cell Biology in the Department of Cell Systems and Anatomy at the UT Health, San Antonio, Texas, USA, In addition to his Ph.D. degree, Dr. Reiter has received three honorary M.D. degrees and one honorary D.Sc. degree from international universities. His research relates to the multiple receptor-independent and receptor-dependent actions of melatonin in humans, animals and plants. He has trained 25 Ph.D. students and 144 postdoctoral fellows. Dr. Reiter has received numerous awards for his research including the A. Ross McIntyre Gold Metal (USA), US Senior Scientist Award (Germany), Lizoni Lincee Award (Italy), Inaugural Aaron B. Lerner Pioneer Award (USA), Chulabhorn Royal Academy Medal (Thailand), etc. He has published numerous research papers, reviews and chapters and he has written or edited 25 books. Based on Google Scholar, his papers have been cited in the scientific literature more than 130,000 times and his h-index is 175. Thomson Reuters/ Clarivate Analytics have identified Dr. Reiter as a Highly Cited Scientist (top 1%) and listed him as one of the World’s Most Influential Scientific Minds in 2014. Dr. Reiter has been an invited speaker at more than 300 international meetings and symposia. He is the Co-Editor of Melatonin Research and he is the Founder and past Editor of the Journal of Pineal Research.
- Charité - University Medicine , Germany
- Title:Prevention of Skin Aging and Skin Cancer by Sunscreens: UV or Light Protection
- Time :
Skin aging is determined not only by genetic aspects but mainly by environmental factors and the lifestyle of each individual. Solar UV-radiation, nicotine and alcohol consumption can cause free radical formation in human skin. In small concentrations free radicals are important for signalling processes, but if their value is exceeding the critical radical concentration, these highly reactive molecules are able to destroy cells or cell compartments. The human organism has developed a protection system against the destructive action of free radicals in form of the antioxidative system. Antioxidants can neutralize free radicals before they can damage the tissue or tissue components.
At the Center of Experimental and Applied Cutaneous Physiology spectroscopic methods were developed to determine the concentration of antioxidants in human skin noninvasively. Based on these measurements the action of free radicals could be estimated by the degradation of the antioxidants. Most antioxidants are not produced in the human organism. They have to be ingested by a healthy diet rich in fruits and vegetables.
The antioxidative potential of the human organism is a fingerprint of the volunteers as determined by their nutritional and stress behavior. Stress factors like sleepiness, illness, alcohol consumption or psychological stress is reducing the concentration of antioxidants in the skin. This was demonstrated by comparing differences in the nutritional and stress behavior of German and Korean citizens. It is well known from the literature that UV irradiation generates free radicals which are reducing the antioxidants in the skin. The same effect could be detected for infrared light, the energy of which is insufficient to produce free radicals by itself. It was found that the infrared radiation stimulates mitochondria, which produce free radicals. These results were confirmed by optical spectroscopic methods and also by paramagnetic resonance spectroscopy. Based on these findings it could be demonstrated that 50% of the free radicals produced by sun radiation in human skin are formed by visible and infrared light. As people applying sunscreens with high protection on the beach are protected against sunburn, these people stay much longer in the sun than if they remained unprotected. In this case, the free radicals produced in the unprotected visible and infrared spectral range of the sun radiation form amounts much higher than the critical radical concentration responsible for skin damage. Protection mechanisms of sunscreens in the visible and infrared spectral range are discussed in the presentation.
Prof. Dr. Dr.-Ing. Jürgen Lademann is an internationally renowned scientist researching at the interface between dermatology, pharmacology and biophysics. Since 1996 the physicist has been in charge of the Center of Experimental and Applied Cutaneous Physiology at the Department of Dermatology, Venerology and Allergology of the Charité – Universitätsmedizin Berlin. In 2001 he was appointed Professor of Dermatology.
He authored and co-authored more than 700 articles in peer-reviewed scientific journals.
He is the President of the “International Foundation of Societies of cosmetic Chemists – IFSCC” and he was the president of the IFSCC Congress 2018 in Munich and many other conferences.
- KOTO Hospital, Japan
- Title:Living Donor Liver Transplantation
- Time :
I have been performing living donor liver transplantation (LDLT), which is the only way to save the life of patients with end-stage liver disease. In June 1990, we performed the first LDLT that case was the first successful case in Japan. The patient remains healthy and is enjoying a normal life still 28 years after the transplant. In 1993, we successfully performed adult-to-adult LDLT, which was the first successful case in the world. The patient enjoyed a normal life for 17 years until she died at 70 years of age. For small children, the left liver of adult donors is too large to close the abdomen. However, in adolescents or adults, even when the whole right liver is used, the volume of the graft is too small. The concept of the standard liver volume (SLV) has proven very important for this procedure and is calculated as follows: 706.2 × body surface area + 2.4. We proposed a method for evaluating the congestion of the liver by Doppler ultrasound. In addition, we devised the right lateral sector graft. Over the years, we have contributed to LDLT in many ways and published many papers. We feel that our findings are quite useful not only for LDLT but also for other hepatectomy procedures.
Dr. Masatoshi Makuuchi is president of the Japanese Red Cross Medical Center, president of the International Association of Surgeons, Gastroenterologists and Oncologists (IASGO) and honorary professor of the University of Tokyo. As a pioneer and a recognized international expert in the field of HBP surgery, Dr. Makuuchi throughout his career, has taken initiatives in developing methods of perioperative managements such as ultrasound guided PTC, BTBD, GB drainage, PVE, intermittent hemihepatic inflow occlusion, warm ischemia in living donor and surgical techniques such as subsegmentectomy, and inferior hepatic vein preserving hepatectomies, contributing to establishing techniques for safe surgical operation.
- Medical University of Vienna ,Austria
- Title: Influence of Adjunctive Classical Homeopathy on Global Health Status and Subjective Wellbeing in Cancer Patients - A Pragmatic Randomized Controlled Trial.
- Time :
The use of complementary and alternative medicine has increased worldwide over the past decade. The aim of this study was to evaluate a possible influence of homeopathy on global health status and subjective wellbeing when used as an add-on to conventional cancer therapy.
In this pragmatic randomized controlled trial, 410 patients, who were treated by standard anti-cancer therapy, were randomized to receive or not receive classical homeopathic add-on therapy. The study was performed at the Medical University Vienna, Department of Medicine I, Clinical Division of Oncology.
Main outcome measures: The main outcome measures were global health status and subjective wellbeing as assessed by the patients. At each of three visits (one baseline, two follow-up visits), patients completed two different questionnaires.
373 patients yielded at least one of three measurements. The improvement of global health status between visits 1 and 3 was significantly stronger in the homeopathy group (p=0.005) when compared with the control group. A significant group difference was also observed with respect to subjective wellbeing (p<0.001) in favor of the homeopathic as compared with the control group. Control patients showed a significant improvement only in subjective wellbeing between their first and third visits. Conclusion: Results suggest that the global health status and subjective wellbeing of cancer patients improve significantly when add-on classical homeopathic treatment is administered. Biography:
Michael Frass, MD, Professor of Medicine, Specialist in Internal Medicine, Homeopathy, Senior Intensivist. Head, Outpatient Unit 2014 to 2019: Homeopathy in malignant Diseases, Division of Clinical Oncology, Department of Internal Medicine I, Medical University Vienna, Austria. Vice President ”Doctors Association for Classical Homeopathy”, President “Austrian Umbrella Association for Medical Holistic Medicine”, Chairperson of WissHom: Scientific Society for Homeopathy. Invention, development, and evaluation of the Esophageal Tracheal Combitube (CombitubeTM, produced by Covidien, Mansfield, Massachusetts, USA). The Combitube is included as a Class IIa device in the Guidelines of the American Heart Association (AHA).
- Leiden University Medical Center, Netherlands.
- Title:Mechanisms of prostate cancer bone metastasis
- Time :
Prostate cancer is the most common cancer in males and a major cause of cancer-related morbidity and mortality in men. Current treatments of prostate cancer with androgen deprivation therapy are initially very effective. Beneficial responses, however, are followed by tumour recurrence at distant sites leading to incurable metastatic castration-resistant disease (mCRPC) including cancer-induced bone disease. Upon bone colonisation, prostate cancer cells alter the physiological balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption, and elicit prevalently an osteoblastic response (osteo-induction). This, in turn, may eventually cause considerable morbidity with bone pain, nerve compression syndromes, pathologic fractures, and myelophthesic anaemia (myelophthisis), i.e. the displacement of hematopoietic bone-marrow by expanding bone metastatic prostate cancer tissue.
In this presentation, mechanism of osteotropism of prostate cancer will be discussed in the context of multiple tumour-stroma interactions, encompassing cell-cell and cell-matrix interactions. Our studies shown that the subpopulation of cancer stem/progenitor cells play a key role in successful bone/bone marrow colonisation. Moreover, we have identified bone marrow/bone-specific stroma response to prostate cancer-induced osteoblastic bone metastasis. A robust induction of gene expression involved in osteogenesis and angiogenesis dominates the osteoblastic bone marrow stromal transcriptome. Strikingly, this translates in an amplification of hematopoietic and prostate epithelial stem cell niche components that may function as a self-reinforcing bone metastatic niche providing a growth support specific for osteo-inductive prostate cancer cells. The induction of this combinatorial stem cell niche is a novel mechanism that may also explain cancer cell osteotropism and local interference with haematopoiesis (myelophthisis). Accordingly, these stem cell niche components may represent innovative therapeutic targets and/or serum biomarkers in osteoblastic bone metastasis.
Prof. Gabri van der Pluijm is a Graduate in Biology with a PhD in Bone Biology from the University of Leiden. After a visting fellow position at the National Institutes of Health (Bethesda, MD, USA) and a senior researcher position at the Leiden University Medical Center, he was appointed as associate professor at the department of Urology and is heading the Urological oncology Research Laboratory. His group developed ‘near-patient’ disease models that are exploited for functional studies, biomedical imaging and drug development studies for prostate, bladder and breast cancer.
Current research -with funding from the EU and national cancer research programmes- is focused on 1. identification of pathophysiological mechanisms of tumour progression and therapy resistance (chemotherapy and castration resistance), 2. development of new, tumour-targeted therapy for urological malignancies (drug development, nanodrug delivery, drug repositioning/repurposing, immunotherapy of cancer) and 3) development and validation of new imaging agents for applied medical imaging of urological malignancies.
He is a board member the European Association for Urology(EAU) (EAU Section Urology Research/ESUR), member of various (inter)national grant review boards, reviewer for multiple international scientific journals, invited/guest lecturer, tutor for medical and biomedical students, member of the Study Programme Committee for Biomedical Sciences at Leiden University, mentor for several PhD students/postdocs. He has served as a co-promotor/external examinator on different national and international PhD (guidance) committees. #publications > 135 original articles. H-index >45.
- Veracruz University Xalapa, Mexico.
- Title:Impact of preganglionar axotomy on neural and hormonal receptors at the prostate of sexually experienced male rats.
- Time :
Cancer is one of the diseases with the highest incidence nowadays. In men, prostate cancer is the most frequent and its incidence increases with age. The used treatment is focused on blocking the effect of androgens, but this is not completely successful because the cases of severe diseases or deaths are still increasing. The underlying reason is still unknown, but an answer could include a possible role of the autonomic nervous system (ANS) that shows a complex innervation to the prostate. This gland is supplied by postganglionic fibers that arrive from the major pelvic ganglion (MPG) that, in turn, is supplied by both the hypogastric nerve (HgN) and the viscerocutaneous branch of the pelvic nerve (PvN). The exact function of this innervation to the prostate is not yet full understood, but it includes a complex circuit of central neurons located at different nuclei of the brain, and some of them are also involved in the control of sexual behavior. MPG is a mixed ganglion because it receives sympathetic (HgN) and parasympathetic (PvN) fibers, and it is proposed that the sympathetic innervation controls prostate growth, while the adrenergic innervation is involved with the control of secretion. On the other hand, it has been reported that alteration in prostate innervation produces inflammatory or proliferative lesions, but its effects on testosterone release are still contradictory. Thus, the purpose of this work was to analyze the effect of sexual behavior and preganglionic axotomy on systemic testosterone levels, gland weight and the expression of androgen, cholinergic and adrenergic receptors. To do this, denervated prostates from intact and sexually experts rats were used. Testosterone levels were analyzed by ELISA and the expression of the receptors was analyzed by Western blot (proteins) and by RT-PCR (messenger). Results indicated that a) Sexual behavior was not affected by axotomy; b) Blood testoterone levels increased due to sexual behavior but is not observed after axotomy; c) The weight of ventral prostate increased with sexual behavior but was not affected by axotomy; d) AR messenger level increased with sexual behavior but were not altered by axotomy; e) The messenger for adrenergic and cholinergic receptors decreased after denervation of both nerves, while for muscarinic receptors increased; f) Only AR protein decreased after axotomy of both nerves. Based on these results, it is concluded that the three receptors have different regulations, and the androgen receptor is the only one that requires the involvement of both nerves to reduce its levels; this could be an important factor to initiate the lesions reported in the prostate.
- South Asian University, India.
- Title:Nanodiamonds inhibits scratch wound repair by blocking cell migration and inhibiting cell proliferation
- Time :
Cell migration is crucial for many physiological and pathological process. Following the lung injury, proliferation and migration of lung epithelial cells to the epithelial lining of alveoli and airways in the lung are pivotal for remodeling and repair of the wound to restore normal lung function. In the present study, we examined the modulatory effect of carboxylated nanodiamonds (cNDs) on the cell division, migration, and adhesion of epithelial cells in the well-established in vitro model of wound repair and cell migration. Flow cytometry and confocal microscopy results indicated that both LA4 and A549 cells effectively internalized fluorescent carboxylated nanodiamonds (cFNDs) and the internalized nanodiamonds were essentially localized in the cytoplasmic region. Treatment with cNDs blocked the division and migration of cells to fill the scratch wound. Live cell imaging and time-lapse videography of the wound healing process indicated a significant inhibition of cell proliferation activity in cND-treated cells and blocked the wound repair process. Trans-well cell-migration assay results further support the inhibitory effect of cNDs on the cell migration process. Western blotting and immunofluorescence staining indicated that the crucial proteins involved in epithelial-mesenchymal transition (EMT) and cell migration i.e. β-catenin, Vimentin, NM-myosin, and Focal Adhesion Kinase (FAK) were downregulated after treatment with cNDs, while the expression of E-cadherin and Claudin-1, major cell adhesion markers remained unaltered. Taken together, our results indicate that the decline in cell proliferation activity, downregulation in the expression of various crucial protein like β-Catenin, NM-myosin, FAK, and Vimentin involved in the cell migration and unaltered expression of cell adhesion molecules E-cadherin and Claudin-1, may be the factors that contribute to the cND-mediated inhibition of EMT during the wound repair process in the monolayers of lung epithelial cells. These results provide an insight into the effect of nanodiamonds on several crucial parameters of EMT and migration of lung epithelial cells. Loss of cell-to-cell adhesion followed by migration are also the factors that facilitate the metastasis of cancer cells. Demonstration that the nanodiamonds can inhibit these cellular properties may also open up the possibility of exploring the use of nanodiamonds as a potential candidate in cancer therapy.
I am Sushreesangita P Behera, a doctoral candidate working under the supervision of Prof. Rajiv K Saxena at South Asian University, India. Our work is mainly focus on the modulation of cell adhesion and migration by carbon nanoparticles in lung epithelial cells. Additionally we are also focussing on lung injury model and tumor metastatic model in the mice.
- Recurrence of paraproteinemic crystalline keratopathy after corneal transplantation, a case of monoclonal gammopathy of ocular significance, Case report.
- Title:Radboud University Medical Centre, Netherlands
- Time :
To present a long term follow-up of a patient with crystalline keratopathy of both eye’s diagnosed with monoclonal gammopathy of undetermined significance (MGUS). Full Thickness corneal transplantation was performed because of significant life threatening visual loss. Recurrence has occurred within a year. Introducing of the term Monoclonal Gammopathy of Ocular Significance is justified in MGUS patients who develop severe crystalline keratopathy with vision impairment. Future therapeutic options to eradicate the plasma clone responsible for the circulating M protein could potentially reduce the risk of recurrence after corneal transplantation.
Dr. Siamak Nobacht, MD, FEBOphth.
Ophthalmologist, director of anterior segment, Cataract & Corneal surgery.
Department of Ophthalmology
Radboud University Medical Centre, Nijmegen, The Netherlands
6500 HB Nijmegen, The Netherlands
- Copenhagen University Hospital,Denmark
- Title:Isolated tumor cells in regional lymph nodes of the esophagus
- Time :
Regional lymph node metastases in patients with carcinoma of the esophagus are an important prognostic factor. According to the eighth edition of the TNM classification of Malignant Tumors isolated tumor cells (ITCs) are defined as ”single tumor cells or small clusters of cells not more than 0.2mm in greatest extent”. Tumor clusters >0.2mm are classified as metastases. The significance of ITCs is unclear. We undertook two studies of carcinomas of the esophagus, one which included 126 patients with adenocarcinoma (AC) of the EGJ and one with 100 patients with squamous cell carcinoma (SCC). All lymph nodes from the resection specimens were carefully examined. In the ACs ITCs were found in 59 of 3454 lymph nodes. Deeper sectioning revealed a change in status from ITCs to metastases in 29 lymph nodes (49.2%).
In the resections from SCCs ITCs were detected in 10 of 2460 lymph nodes. Deeper sectioning detected metastases in 5 of these (50%).
To obtain an accurate pN category we strongly recommend thorough examination of regional lymph nodes and additional sectioning when ITCs are found.
MD Copenhagen University
Primary examination of the Royal College of Pathologists, London 1980
Callender-Binford Fellowship, Armed Forces Institute of Pathology, Washington DC 1985-87
Certified as a specialist in pathology Copenhagen University 1989
Two years in London (one year at St Stephen’s Hospital 1978-1979, and one year at the Royal Free Hospital 1979 -1980)
Eight years at the Armed Forces Institute of Pathology, Washington DC (1984-1989, and 2001-2005, the latter as a visiting scientist).
In between these “out of my country” employments, I have worked at various hospitals in Copenhagen. For the past 15 years I have worked at Copenhagen University Hospital in the dept. of GI pathology. I have dealt with CUP for the past nine years. Also I am part of the hospital’s Center of Excellence for neuroendocrine tumors. My main focus of research is neuroendocrine tumors of the GI tract and the lungs and gastrointestinal pathology.
- Faculty of Medicine of University of Porto, Portugal
- Title:PD-1 blockade as a future treatment for colorectal cancer with microsatellite instability
- Time :
Colorectal cancer is the third most common cancer worldwide, with about 15% of these tumours related with microsatellite instability, which confers distinct characteristics to these tumours, both clinicopathological and in the response to treatments. In fact, the poor response to chemotherapy in these tumours has led to the investigation for new treatments, with immunotherapy being the most successful one to date. The focus of this review is to assess the response of microsatellite unstable colorectal cancer to PD-1 blockade, and the mechanisms behind that response. A PubMed research was conducted, resulting in the inclusion of 47 articles in this review. Microsatellite instability results in a high neoantigen load, leading to a highly active immune microenvironment of the tumour, mainly due to T-cells. To counteract this, there is an upregulation of PD-1, acting as a “brake” for immune cells, facilitating tumour growth and metastasis. This upregulation makes these tumours great candidates for treatment with PD-1 blockade, as seen in many clinical trials, where the overall responses and progression free survival rates were higher than those observed in microsatellite stable tumours. With the importance of colorectal cancer with microsatellite instability new treatments are necessary. Therefore, PD-1 blockade is a promising treatment for colorectal cancer with microsatellite instability, with improvement in survival rates and a better prognosis for these patients.
Born in Porto in 1996. Attended the Faculty of Medicine of University of Porto with a Master’s Degree in Medicine, graduating in 2020. My interest in the Oncology field begun early in Medical School and I have been keen on learning about cancer, mainly how patients can be treated and what can be done to improve the patients’ quality of life. Furthermore, microsatellite instability and its role in cancer development and treatment modalities has been important in my life for many years, making this the object of my interest.
- Moffitt Cancer Center,USA
- Title:Cancer: Personal, Professional and Practice Impact
- Time :
My family’s journey in managing my husband’s battle with Stage IV Colorectal Cancer has been an eye-opener to the inequities in Healthcare, not only amongst the insured and uninsured but also within the insured subgroup. It has motivated us to develop ways to narrow this gap and changed our practice of medicine. It has pushed me out of my comfort zone to change positions from the Medical Director of a large, established hospitalist group to the Chair of Medicine at a top 10 U.S. News and World Report Cancer Center which is also a Center of Academic Excellence. I felt the latter would offer more challenges and opportunities to make a difference in Cancer Care in all populations as well as motivate physicians in training to do the same.
Dr. Asha Ramsakal is the Chair of the Department of Medicine at Moffitt Cancer Center. Moffitt Cancer Center is ranked number eight in US News and World Report top cancer hospitals nationwide. It is at the very forefront of cancer centers worldwide in pioneering advances like CAR T-cell therapy, a promising approach to immunotherapy that uses a patient’s own immune cells to recognize and attack their tumors.
Dr. Ramsakal is also an Associate Professor at the University of South Florida Morsani College of Medicine and provides direct oversight of Internal Medicine Resident Education at Moffitt with an active didactic role and the goal of making board certified, competent, compassionate physicians. She has instructed medical students, residents, and interns on the discipline of internal medicine and interdisciplinary oncology for more than two decades. Dr. Ramsakal is well published; she’s written several book chapters on oncologic emergencies and many articles on infections in cancer patients as well as nouvel therapies for the unique complications of immune mediated sequela of check-point inhibitors.
Her clinical interests include the optimal management of medical comorbidities and treatment sequela in cancer patients by academic oncologic hospitalists. Previously, Dr. Ramsakal was Medical Director of the Baycare Medical Group East Region Hospitalist and Palliative Care Programs.
Dr. Ramsakal earned her DO medical degree at Nova-Southeastern University at Ft. Lauderdale followed by an internal medicine residency at the University of South Florida College of Medicine in Tampa. She was also the Chief Medicine Resident at the James A. Haley VA Hospital. She is board certified by the American Board of Internal Medicine.
She has been nominated as one of America’s Top Physicians, America’s Top Internist, has been featured in Top Doctor’s Magazine 2019 and she is listed in America’s Registry of Outstanding Professionals as a Lifetime Member for Outstanding Contribution to Professionals and the Community. She has been the recipient of the “University of South Florida Outstanding Resident Teaching Award at Moffitt Cancer Center” four times and was named “Florida American College of Physicians Outstanding Teacher of the Year.”
Additional attributes are the depth and breadth of her committee participation and leadership and her history of community outreach locally and abroad. Dr. Ramsakal dedicates time each year to provide voluntary medical services to underserved Honduran and Guatemalan villages.
- University of Buffalo, USA
- Title:A Single Centre Report and Meta-Analysis of Primary and Secondary Breast Angiosarcoma
- Time :
Background: Primary and secondary breast angiosarcoma is a rare and aggressive malignancy with limited published literature. Optimal management is mostly based on expert opinion. Our study aims to describe a single institution experience with breast angiosarcoma and evaluate other publications on this topic to further clarify prognostic outcomes and treatment modalities in this disease.
Methods: 22 cases of breast angiosarcoma from Roswell Park Comprehensive Cancer Center were retrospectively analyzed. Additionally, a systemic review and meta-analysis was conducted to study the association between survival outcomes; overall survival (OS) and recurrence-free survival (RFS) in both primary (PAS) and secondary breast angiosarcoma (SAS).
Results: 9 PAS patients (41%) and 13 SAS patients (59%) were retrospectively analyzed. No significant differences were noted in tumor characteristics and survival outcomes between PAS and SAS. Treatment modality had no significant effects on survival outcomes although adjuvant chemotherapy demonstrated a trend towards improved RFS in high grade tumors. 380 PAS and 595 SAS patients were included in the outcome meta-analysis. Survival outcomes were significantly worse with high grade tumors and tumor size of >5cm. Adjuvant radiation therapy demonstrated significantly better RFS, while adjuvant chemotherapy had no effect on survival outcomes.
Conclusion: Tumor size and grade seem to be reliable predictors of survival in both PAS and SAS. Mastectomy does not seem to be adding any additional benefit to BCS. Adjuvant radiation therapy showed statistically significant RFS benefit, while adjuvant chemotherapy can be beneficial in high grade tumors.
Dr. Yara Abdou was born in Dubai, United Arab Emirates. She obtained her medical degree from Jordan University and then finished a year of research fellowship at the Mayo Clinic, Rochester, MN, USA. Her internal medicine residency was completed at University of New Mexico, Albuquerque, USA. She completed her hematology and oncology fellowship at Roswell Park Comprehensive Cancer Center, affiliated with the University of Buffalo, USA. She is transitioning to a breast medical oncology faculty position in 2020.
Dr. Abdou’s research interests mainly involve studying the tumor microenvironment and ways of modulating immune responses to enhance immunotherapy in breast cancer patients. She has also been recently focusing on studying the tumor microenvironment in African American women and exploring how their immune responses may be contributing to breast cancer racial disparities.
- Ben-Gurion University of the Negev, Israel
- Title:The Mitochondrial Voltage-Dependent Anion Channel 1 in Tumor Cells.
- Time :
Shoshan-Barmatz laboratory focuses on VDAC1, a protein located in the outer mitochondrial membrane that acts as a gatekeeper of mitochondrial functions, including metabolism and energy production. VDAC1 serves as a hub protein, interacting with various other proteins. Its interactome includes proteins associated with DNA and RNA maintenance, and proteins involved in metabolism, apoptosis, signal transduction, and anti-oxidation, and more. This enables the regulation and integration of mitochondrial functions with other cellular activities.
The numerous roles played by VDAC1, as well as its overexpression in disease states, led the Shoshan-Barmatz group to develop several VDAC1-based strategies that lead to dramatic effects on various diseases considered as metabolic diseases, all of which are characterized by VDAC1 overexpression and altered cell metabolism and/or apoptosis. Their studies involve a variety of approaches, such as molecular biology, protein purification, electrophysiology (for monitoring single-channel activity), tissue culture, and the use of animal models for various diseases (e.g., breast, liver, and lung cancers, melanomas, glioblastoma, Alzheimer’s disease, and type 2 diabetes). As such, Prof. Shoshan-Barmatz and her team were able to develop and test VDAC1-based strategies simultaneously attacking several cancer hallmarks, and for use in treating type 2 diabetes, Alzheimer’s disease, and cardiovascular diseases. These VDAC1-based strategies include several VDAC1-interacting small molecules, VDAC1-based peptides, and VDAC1-specific siRNA, all of which have been validated in vitro and in vivo and are protected by dozens of patents.
Varda Shoshan Barmatz is the Hyman-Kreitman Chair in Bioenergetics at Ben-Gurion University (BGU). Her PhD is from the Weizmann Institute; Post-doctoral training was from the University of Wisconsin-Madison and the University of Toronto. In 1982, she joined the Department of Life Sciences, BGU, and served as Chair (2000-2004). Her awards include the Hestrin Prize of the Israel Biochemistry Society, Teva Award for Young Scientists (1993) and Teva Founders Award (2016). Lady Globes magazine selected her as one of the 50 most infl uential women in Israel (2009) and one of five who made breakthroughs in science (2016). She was the Founder and Director (2006-2015) of the National Institute for Biotechnology in the Negev.
- University of Texas ,USA
- Title:Mechanism-based Optimization of the Conditioning Regimen for Hematopoietic Stem Cell Transplantation
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Hematopoietic stem cell transplantation (HSCT) is effective for hematological disorders. Its success partly depends on the efficacy of the conditioning regimen. To identify efficacious regimens, we exposed cells to various drug combinations, analyzed their cytotoxicity and identified their molecular mechanisms of interaction. We have shown the synergistic cytotoxicity of DNA alkylating agents (AA) and nucleoside analogs (NA) and proposed a mechanistic model -the “loop of death”. NA initiates DNA damage resulting in chromatin remodeling and makes genomic DNA more susceptible to DNA alkylation. DNA damage response (DDR) is activated and the loop of DNA damage, chromatin remodeling, and DNA alkylation continues until the tumor cells commit to apoptosis. Using this model, we hypothesized that epigenetic modifiers would amplify the loop of death. Indeed, inhibitors of histone deacetylases (HDACi) and DNA methyl transferases (DNMTi), which facilitate relaxation of chromatin, were found to be synergistic with AA+NA. Since active DNA repair may contribute to decreased efficacy of these drug combinations, we also examined the inclusion of DNA repair inhibitor olaparib. Addition of olaparib to a [AA+NA] combination caused significant apoptosis by activation of the DDR, inhibition of PARP activity and DNA repair, production of reactive oxygen species and depolarization of the mitochondrial membranes. Most of our pre-clinical studies have been translated to the clinic and results from some of our clinical trials will be presented. Overall, our pre-clinical and clinical results suggest that the conditioning regimen for HSCT may be optimized by combining drugs that provide synergistic cytotoxicity based on their molecular mechanisms of action.
Ben Valdez obtained his PhD in Biochem at Louisiana State Univ. He did his post-doctoral training at Baylor College of Medicine and became an Assistant Professor. His laboratory cloned the genes and corresponding cDNAs for RNA helicase II/Gu α and β and discovered their functions. His lab identified the functions of treacle, encoded by the TCOF1 gene, in the expression and methylation of pre-ribosomal RNA. He moved to MD Anderson Cancer Center in 2005 where he is now an Associate Professor. His current research focuses on the identification of safe and efficacious conditioning regimen for HSCT for patients with blood disorders. He conceptualized and proved the efficacy of combined DNA alkylators, nucleoside analogs, and epigenetic modifiers in leukemia, lymphoma and multiple myeloma, and proposed a model called the “loop of death” to explain their cytotoxic synergism. He developed an assay for cellular efflux of chemotherapeutic drugs which is relevant to understanding drug interactions. The results of his pre-clinical studies have been used as bases for several clinical trials at MD Anderson Cancer Center.
- State University of Campinas-UNICAMP , Brazil
- Title:Comparative Study of Phototoxicity of Protoporphyrin IX Synthetic and Extracted from ssp Rattus Novergicus Albinus Rats toward Murine Melanoma Cells
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Protoporphyrin IX (PpIX) is a precursor of heme synthesis and is known to be an active photosensitizer and precursor of photosensitizers applied in photodynamic therapy (PDT) and photodynamic diagnostics (PDD). On irradiation with visible light, PpIX undergoes phototransformation, producing photoproducts which may also be phototoxic and increase its efficacy. The mechanism of PpIX phototransformation depends on environmental characteristics and can be different in vitro and in vivo. In this paper, we present a comparative study of the photoactivity of synthetic PpIX and PpIX extracted from the Harderian gland of ssp Rattus novergicus albinus rats, along with their photoproducts toward murine B16F-10 melanoma cells. It was observed that when irradiated with visible light the endogenous PpIX demonstrates photocytotoxicity ten times higher than the synthetic PpIX. The photoproduct of endogenous PpIX also possesses phototoxicity, though slightly lower than that of PpIX itself. The rate of cell internalization for both endogenous PpIX and its photoproduct was eightfold greater than that obtained for the synthetic porphyrin. This difference might result from a complexation of the native PpIX with some amphiphilic compounds during its synthesis within the Harderian glands, which facilitates the cell uptake of PpIX. Fluorescence microscopy images show that both endogenous and synthetic porphyrins are localized after uptake predominantly in the mitochondrial region of cells.
Graduated in Biological Sciences Medical Modality from the State University of Campinas, Master in Genetics and Molecular Biology from the State University of Campinas and PhD in Medical Sciences from the State University of Campinas. Post Doctorate in Medical Physics, University of São Paulo Campus Ribeirão Preto, CNPq. Today I work as a biomedical in the laser laboratory of Medicine and Surgery Experimental Center, Faculty of Medical Sciences, State University of Campinas, I’m membership of the PanAmerican Society for Photodynamic Therapy (PAPDT). I have experience in Biology and Biomedicine, focusing on Photobiophysics and Photomedicine, working mainly in basic research on the following topics: interaction of biological and photoactive compounds with biological systems, in the investigation of parameters associated with endogenous protoporphyrin IX and low power laser in biological tissues.
- Washington University , USA
- Title:Checkpoint Immunotherapy Markers for Pediatric Tumors with Driver Mutations
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Great advances have taken place in the understanding and treatment of pediatric malignant tumors for the past a few decades. However, challenges still exist such as lack of efficient treatments for certain tumors and the side effects and impact of the current treatment options on the growth and development of children with these tumors. Tumor checkpoint blockade immunotherapy has received considerable attention and success in a broad range of tumors including melanoma and non-small cell lung cancer (NSCLC). Dr. He and his collaborators have been working on markers for checkpoint Immunotherapy for pediatric malignant tumors with driver mutations including malignant rhabdoid tumor, NUT midline carcinoma, synovial sarcoma and so on.
Dr. Mai (Mike) He, M.D., Ph.D., is currently an associate professor and section head of Pediatric Pathology in the Department of Pathology & Immunology, Washington University at St. Louis School of Medicine. He is also the Pathologist-in-chief at St. Louis Children’s Hospital. Dr. He received his medical degree from Fudan University Medical Center (formerly Shanghai Medical University), Shanghai, China and his Ph.D. from the Graduate School of Biomedical Science, Rutgers University, Newark, New Jersey. Dr. He completed his AP/CP residency training in Rutgers University New Jersey Medical School, Newark, New Jersey. He had a few additional fellowship training including Molecular and Genetic Pathology (MGP) in the Memorial Sloan Kettering Cancer Center, New York, New York, and is board certified in AP, CP, MGP and Pediatric Pathology. His research interest includes potential targeted and immunotherapy for pediatric cancer.
- Shanghai Jiao Tong University ,China
- Title:Non-Platelet-Derived CXCL4 Differentially Regulates Cytotoxic and Regulatory T cells through CXCR3 to Suppress the Immune Response to Colon Cancer
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CXCL4 is mainly produced by activated platelets, but certain somatic cells and cancer cells also express CXCL4. However, the physiological function of non-platelet-derived CXCL4 is unclear. Previously we reported that CXCL4 produced by cancer cells accelerated tumor growth by suppressing the antitumor activities of cytotoxic T lymphocytes (CTLs). To elucidate the mechanism of CXCL4 in tumor immunity, we compared the CTLs and regulatory T cells (Tregs) from CXCL4−/−, CXCR3−/− and C57BL/6 mice overexpressing CXCL4 via intramuscular electroporation. CXCL4 accelerated tumor growth in CXCL4−/− and C57BL/6 mice but not in CXCR3−/− mice. Furthermore, CXCL4 decreased CTLs proliferation and IFN-γ production and enhanced CTLs apoptosis and programmed death 1 (PD-1) expression. Conversely, CXCL4 promoted Tregs proliferation and TGF-β production and downregulated PD-1 expression in Tregs. Notably, these effects of CXCL4 were both observed in the splenic and tumor-infiltrating CTLs and Tregs from wild-type but not CXCR3−/− mice. Here we revealed a negative immune regulatory function for non-platelet-derived CXCL4 through CXCR3 that cancer cells could hijack to evade the host immune system, suggesting that the CXCL4/CXCR3 axis may serve as a novel target for colorectal cancer immunotherapy.
Dr. Wei Han completed his Ph.D. in Molecular Biology from Mount Sinai School of Medicine at NYC in 1994 followed by a postdoctoral training at Memorial Sloan-Kettering Cancer Center. He is now a professor at Shanghai Jiao Tong University and Founder of General Regeneratives (Shanghai) Ltd. He developed a proprietary “Prometheus Technology” to discover genes important for multiple tissue regeneration and repair, including bone marrow, liver, pancreas, cartilage, gut epithelial, and thymus. Over the years, a series of investigational new drugs were developed. The most advanced candidate with global patents, GR007, a multi-organ protector against chemotoxicities has demonstrated its good safety profile and preliminary efficacy in phase 1 clinical trial, and phase 2 clinical trial is ongoing.
- Universidad de Santiago de Chile, Chile
- Title:Preparation of Novel Homodimers Derived from Cytotoxic Isoquinolinequinones. A Twin Drug Approach.
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The synthesis of novel homodimers is reported based on the anilinoisoquinolinequinone scaffold. In these twin-drug derivatives, two units of the anilinoquinone pharmacophores are linked through a methylene spacer. The formation of dimers was achieved by reaction of isoquinolinequinones with 4, 4′-diaminodiphenylmethane via a sequence of two oxidative amination reactions. A preliminary in vitro screening of the homodimers reveals moderate to high cytotoxic activities against MDA-MB-21 breast adenocarcinoma and B16-F10 murine metastatic melanoma cell lines. The asymmetrical homodimer stands out due to its cytotoxic potencies at submicromolar concentrations and high selectivity index (mean IC50 = 0.37 μM; SI = 6.97) compared to those of etoposide (mean IC50 = 3.67; SI = 0.32) and taxol (mean IC50 = 0.35; SI = 0.91) employed as reference anticancer drugs.
Juana A. Ibacache complete her PhD in Chemistry at the Pontificia Universidad Catolica de Chile under the supervision of Prof. Jaime A. Valderrama. The research carried out by Ibacache during her PhD studies were focused in synthesis of new aminoisoquinolin- and aminofenantridinequinone derivatives and study antitumor activity in four cancer cell lines. I carry out studies of structure activity relating the antitumor activity with physicochemical parameters such as redox potentials and lipophilicity. In 2012 she continued with postdoctoral studies and She is now a professor at Universidad de Santiago de Chile. Juana A. Ibacache does research in designed and synthesis of quinones N-heterocyclic, hodimers and heterodimers based in quinones with biological activity.
- Medical University of South Carolina, USA
- Title:Automatically Identifying Social Isolation from Clinical Narratives for Patients with Prostate Cancer
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Social isolation is an important social determinant that impacts health outcomes and mortality among patients. The National Academy of Medicine recently recommended to document social isolation in electronic health records(EHR). However, social isolation usually is not recorded as coded data but rather collected from patient self-report or documented in clinical narratives. This study explores natural language processing (NLP) strategy for identifying socially isolated patients from clinical narratives. We used data from the Medical University of South Carolina (MUSC) Research Data Warehouse. Patients 18 years-of-age or older who were diagnosed with prostate cancer between January 1, 2014 and May 31, 2017 were eligible. Of 4,195 eligible prostate cancer patients, we randomly sampled 3,138 patients (75%) as a training dataset. The remaining 1,057 patients (25%) were used as a test dataset to evaluate NLP algorithm performance. A total of 55,516 clinical notes from 3,138 patients were included to develop the lexicon and NLP pipelines for social isolation. Of those, 35 unique patients (1.2%) had social isolation mention(s) in 217 notes. Among 24 terms relevant to social isolation, the most prevalent were “lack of social support,” “lonely,” “social isolation,” “no friends,” and “loneliness”. Among 1,057 patients in the test dataset, 17 patients (1.6%) were identified as having social isolation mention(s) in 40 clinical notes. Domain expert Manual review identified 4 false positive mentions of social isolation and 1 false negatives in 154 notes from randomly selected 52 controls. The NLP pipeline demonstrated 90% precision, 97% recall, and 93% F-measure.
Vivienne Zhu, MD, MS is an assistant professor in the Biomedical Informatics Center (BMIC) at the Medical University of South Carolina (MUSC). Dr. Zhu’s major research area is improving quality of care and health outcomes for patients with chronic conditions using health information technology (HIT). Her expertise incldue computerized clinical decision support (CDSS), electrinic health record (EHR), natural languge processing (NLP) for clincal appliaitons, and predictive analytics. At MUSC, using NLP technology, Dr. Zhu led effort of measuring compliance rate of the Joint Commission standards for critical results reporting and communication and the CMS quality of care reporting. Dr. Zhu is the pricinple investigator and co-investigator for serveral NIH funded studies. She leads an NLP project of identifying and extracting social determinates from clinical notes for prostaet cancer patients. Dr.Zhu has published a nubmer of peer-reviewed scientific papers on medical informatics, patient safety, and health outcomes research
- University of Cambridge, United Kingdom
- Title:Metallic Nanoparticles for Biomedical Applications of Surface Enhanced Raman Spectroscopy
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The advent of nanotechnology has opened up enormous opportunities in the bio-sensing area, allowing the fabrication of constructs that are small enough to be targeted in the interior of single living cells and their intracellular compartments. Nanotechnology has great potential for diagnosis, therapy and treatment, its numerous applications in clinical practice have already emerged giving rise to the contemporary fast growing field of nanomedicine. In the last two decades, the localized surface plasmon resonance (LSPR) effect of noble metallic nanoparticles (MNPs) has been the subject of intense research efforts. This effect is exploited in Surface Enhanced Raman Spectroscopy (SERS), a molecular detection method which provides high sensitivity and specificity. In recent years, it has been reported that SERS is one of the leading techniques for molecular analysis with sensitivity up to the single molecule. Owing to this tremendous signal enhancement, SERS has been the object of great interest in many areas of science and technology including chemical analysis, catalysis, biological sensors, imaging and sensing leading to both diagnostics and therapies. MNPs have been used in various areas of medical treatment: they are emerging as new carrier and contrast agents in cancer treatment combining both diagnosis (imaging) and selective therapy. Furthermore, they have been used for imaging of tumor cells. In fact, once in place, these nano-objects when decorated with suitable molecular reporters can be readily traced by different spectroscopic techniques, thus allowing their localization in the cellular environment.
Marianna Pannico is a researcher at the Institute for Polymers, Composites and Biomaterials (IPCB) of the National Research Council of Italy. She is doctor in Chemistry and in 2010 she got her Ph.D in Materials and Structures Engineering at University of Napoli “Federico II”. She is an Adjunct Assistant Professor of Chemistry and Math at “University of Maryland University College (UMUC)” Europe. She does research in Physical Chemistry, Polymer Chemistry and Materials Chemistry. Her research activity in mainly focused on plasmonic nanomaterials for the analytical and bio-sensing applications of SERS spectroscopy. She is an expert of Raman Spectroscopy, confocal Raman imaging, Surface Enhanced Raman Spectroscopy (SERS) and Infrared spectroscopy (FTIR, FT-NIR, IR microspectroscopy). She is really interested in theranostic applications of metallic nanoparticles in nanomedicine.
- University of Milan, Italy
- Title:Drug Delivery Systems For Cancer Treatment
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Cancer is still a leading cause of death worldwide. Despite the improvements achieved in cancer therapy the outcome is still partially ineffective against different cancer types. Therefore, there is dramatic need to develop novel treatment modalities. Among the novel therapeutic strategies the use of oncolytic viruses (OVs), which are specifically engineered to selectively infect, replicate in and kill cancer cells, is one of the most promising approach. Even though promising efficacy has been observed in preclinical in vitro and in vivo studies, OVs are often administered intra-tumorally (i.t.), thus many solid tumors cannot be treated using this approach. Extracellular vesicles (EVs) are nanometer- to micron-sized lipid bilayered vesicles able to shuttle biological molecules, such as OVs, even over longer distances. We demonstrated that loading EVs with OVs increased their anti-neoplastic activity compared to the virus or EVs alone. Interestingly, this activity was observed even if the EVs derived from lung cancer were applied to colon carcinoma cell lines and vice versa, suggesting that the EV uptake occurred in vitro without any specificity for the cancer cells from which the vesicles originated. When administered intravenously to the mouse models of cancer, the tumour-derived EVs, demonstrated a selective accumulation of the fluorescence at the tumour site 24 h after injection; confirming the generalized tropism of tumour-derived EVs for any neoplastic tissue, independent of the tumour type or even the species originating the vesicles. Our findings opens new way for the selective delivery of diagnostic/therapeutic agents to solid tumours.
M.Garofalo got a PhD in Biochemistry and Cell and Molecular Biology in 2015 from University Federico II of Naples (Italy) with a foreign co-advisor from University of Helsinki (Finland). After a post-doc at University of Helsinki, her current research is focused on the definition of tools and techniques to improve the delivery of biological drugs and chemotherapeutic agents using oncolytic adenoviruses and extracellular vesicles
- National Medical University ,Ukraine
- Title:Interdisciplinary Synergetic Dialogue between Physics and Medicine
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The effectiveness of the synergеtic approach is based on the ability to transfer the results of one science (e.g. physics), being more “simple” and accurate due to omitting many details that can be considered inessential, to objects of other science (e.g. medicine) which are much more complicated and therefore can be described rather qualitatively than quantitatively. This presentation aims to use the synergetic isomorphism (similarity) between carcinogenesis and nucleation (new phase formation) and to suggest a new possible mechanism to prevent the growth of malignant tumors.
The fundamental results of the nucleation theory and its medical application to the problem of cancer therapy give us a possibility to formulate the necessary conditions which could help to prevent the formation and uncontrollable growth of pathological tumors: (a) the critical size of new phase nuclei, which grow into a malignant tumor, is directly proportional to the coefficient of surface tension; (b) the magnitude of the nucleation barrier, which should be overcome for the emergence of capable embryos and the further growth of such supercritical nuclei, is directly proportional to the cube of the coefficient of surface tension; (c) if the size of a new phase nucleus is less than its critical size, then an energetically favorable process is to further reduce the size, i.e. such subcritical nuclei are spontaneously decreasing their sizes. Thus, such an interdisciplinary dialogue between medicine and physics allows us to formulate the hypothesis of preventing the process of tumor’s growth by using appropriate surface-inactive substances, which increase the surface tension coefficient.
The confirmation of theoretical consequences based on the above-mentioned hypothesis requires undoubtedly further experimental studies and careful selection of effective non-toxic surface-inactive substances. At the same time, we would like to believe that an attractive idea of synergetic isomorphism of similar phenomena in open non-equilibrium systems of different nature, which has already proved its effectiveness in a large number of studies, will be useful in cancer therapy for a deeper understanding the carcinogenesis processes and preventing the cancer tumors formation.
Prof. Alexander V. Chalyi currently works at the Department of Medical and Biological Physics and Informatics, Bogomolets National Medical University (Kyiv, Ukraine), being Head of Department. Alexander does research in Condensed Matter Physics, Biophysics and Atomic, Molecular and Optical Physics, Medical Physics, Synergetics, Phase transitions and critical phenomena, Neutron Optics. His current projects are ‘Diffusion anomalies in nanoscale systems and sypercooled water’, ‘Surface tension in bulk and bounded liquids’, ‘Interdisciplinary dialogue between physics and medicine’.
- Cairo University, Egypt
- Title:Telluric Acid Ameliorates Hepatic Ischemia Reperfusion-Induced Injury in Rats: Involvement of TLR4, Nrf2, and PI3K/Akt Signaling Pathways.
- Time :
Background: Hepatic ischemia reperfusion (IR) injury is an inevitable risk after liver transplantation, characterized by a plethora of events leading to hepatocellular injury. Indeed, hepatic IR injury triggers high-mobility group box protein B1 (HMGB1) release that activates toll like receptor-4 (TLR4) and initiates a downstream signaling cascade to activate mitogen activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) to produce inflammatory cytokines and chemokines as well as a state of oxidative stress. On the other hand, the endogenous negative feedback regulator, phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) axis, that reduces pro-inflammatory and apoptotic insults was inhibited and the expression nuclear erythroid-related factor-2 (Nrf-2) pathway that enhances the expression of antioxidant enzymes was downregulated.
Objective: This study examined the potential hepatoprotective effect of telluric acid (TELL), one of tellurium based compound, against the devastating effect of hepatic IR injury. In past, tellurium based compound had limited functional use, however they acquired considerable interest nowadays due to antioxidant and anti-inflammatory activities. The current study targeted HMGB1/ TLR4 cascade, in addition to PI3K/ Akt axis, and Nrf-2 pathway as possible mechanisms contributed to TELL’s effect.
Methods: Male Wistar rats were allocated into 3 groups (n=10): sham-operated, control IR and TELL (50 μg/kg). TELL was administrated once daily for seven consecutive days prior to the IR induction. Hepatic IR injury was established by inhibiting the blood supply to the left lateral and median hepatic lobes, which constitutes 70% of the rat liver mass.
Results: Pretreatment with TELL mitigated hepatic IR injury as manifested by decreased plasma aminotransaminases and lactate dehydrogenase activities. Also, TELL opposed IR induced elevation in tissue expression/activity of HMGB1, TLR4, myeloid differentiation primary-response protein 88 (MyD88), p-NF-κB p65, p-MAPKp38 and tumor necrosis factor-alpha (TNF-α). Moreover, TELL reduced the elevated thiobarbituric acid reactive substances along with increased both Nrf-2 and endothelial nitric oxide synthase (eNOS) protein expression, beside replenishment of hepatic reduced glutathione. In addition, TELL induced obvious upregulation of p-PI3K and p-Akt protein expressions together with restoration of histopathological changes in IR injury.
Conclusions: TELL purveyed conceivable novel hepatoprotective mechanisms and attenuated events associated with acute hepatic injury via inhibition of TLR4 downstream axis and activation of Nrf-2 and PI3K/Akt signaling cascades. Thus, TELL may provide a novel therapeutic potential for complications of hepatic IR injury.
Bachelor degree in Pharmaceutical Sciences from Faculty of Pharmacy, Cairo University, May 2011
Master degree in Pharmaceutical Sciences (Pharmacology & Toxicology) from Faculty of Pharmacy, Cairo University, 2015
Doctor of Philosophy in Pharmaceutical Sciences (Pharmacology & Toxicology) from Faculty of Pharmacy, Cairo University, 2018
Career History and Professional Experience:
Lecturer of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University
Assistant Vice Dean for Graduates and Research Affairs, Faculty of Pharmacy, Cairo University
General Coordinator of Continuous Pharmacy Education Center, Faculty of Pharmacy, Cairo University
Member of Science and Technology Development Fund (STDF) research grant project entitled “To Determine the Capability of the Cardioprotective Cyclocreatine Phosphate to Reduce the Progression of Myocardial Infarction to Heart Failure in the Standard ISO Rat Model” (2018).
Member of the Erasmus project entitled “IT-based international diploma and professional certificate in clinical toxicology”-ITCT (2015).
Research interest and Publications:
Research interest: Molecular Neuropharmacology, Clinical Toxicology, Signal transduction pathways, Neuroscience, Inflammation, Pharmacovigilance and Gastrointestinal system.
Telluric acid ameliorates hepatic ischemia reperfusion-induced injury in rats: Involvement of TLR4, Nrf2, and PI3K/Akt signaling pathways “published at Biochemical Pharmacology 168 (2019):404-411, August 2019.
The Mas receptor as a future perspective in Parkinson’s disease “published at Journal of Neurology & Neuromedicine 3(4): 65-68, August 2018
Neurorestorative role of intrastriatal angiotensin 1-7 in 6-hydroxydopamine hemiparkinsonism by dual angiotensin 1-7/MASR axis activation and HMGB-1/RAGE signaling inhibition “published at World Congress of Pharmacology, Kyoto, Japan, July 2018
Angiotensin 1-7 ameliorates 6-hydroxydopamine lesions in hemiparkinsonian rats through activation of MAS receptor/PI3K/Akt/BDNF pathway and inhibition of angiotensin II type-1 receptor/NF-κB axis “published at Biochemical Pharmacology 151 (2018) 126–134, February 2018.
- Hamad General Hospital ,Qatar
- Title:Cystic Poorly Differentiated Squamous Cell Carcinoma of the Scalp, a Rare Scalp Tumor: Case Report and Literature Review.
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Cutaneous cystic lesions have broad differentials ranging from common benign entity to rare malignant lesions. Clinical evaluation of the lesion is the key to differentiation, as some rare malignant entities may simulate benign lesions. A high index of suspicion should be maintained for any aggressive behavior, which may require more thorough evaluation, including histopathology and radiographic imaging studies. We report a rare case of cystic poorly differentiated squamous cell carcinoma (CPDSCC) of the scalp.
We report a case of a 37-year-old Filipino expatriate male who presented with a scalp swelling which had been gradually increasing in size for four months and was operated upon with a working diagnosis of sebaceous cyst. On post-op excisional biopsy, it turned out to be poorly differentiated cystic squamous cell carcinoma of the scalp. On further workup, no metastasis or other primary was found. Complete re-excision of the lesion with no evidence of residual tumor was achieved. Long-term follow-up was lost, as the patient left for his native country.
Though cystic cutaneous lesions are very commonly encountered in clinical practice, high suspicion for malignancy should be maintained if the lesion shows any aggressive behavior. Prompt investigation should be done before surgery to determine the nature of the disease and the most effective management for the patient. Poorly differentiated cystic squamous cell carcinoma should also be considered in the differential diagnosis of cystic cutaneous lesions show aggressive behavior.
Dr Amjad Shah , Specialist Acute care surgery of General surgery department , Hamad General Hospital , Doha , Qatar.
- King Abdullah International Medical Research Centre , Saudi Arabia
- Title:Biological Impact of Advanced Glycation End-Products on Estrogen Receptor-Positive MCF-7 Breast Cancer Cells
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Diabetes mellitus potentiates the risk of breast cancer. We have previously described the pro-tumorigenic effects of advanced glycation end-products (AGEs) on estrogen receptor (ER)-negative MDA-MB-231 breast cancer cell line mediated through the receptor for AGEs (RAGE). However, a predominant association between women with ER-positive breast cancer and type 2 diabetes mellitus has been reported. Therefore, we have investigated the biological impacts of AGEs on ER-positive human breast cancer cell line MCF-7 using in vitro cell-based assays including cell count, migration, and invasion assays. Western blot, FACS analyses and quantitative real time-PCR were also performed. We found that AGEs at 50-100 g/mL increased MCF-7 cell proliferation and cell migration associated with an enhancement of pro-matrix metalloproteinase (MMP)-9 activity, without affecting their poor invasiveness. However, 200 g/mL AGEs inhibited MCF-7 cell proliferation through induction of apoptosis indicated by caspase-3 cleavage detected using Western blotting. A phospho-protein array analysis revealed that AGEs mainly induce the phosphorylation of extracellular-signal regulated kinase (ERK)1/2 and cAMP response element binding protein-1 (CREB1), both signaling molecules considered as key regulators of AGEs pro-tumorigenic effects. We also showed that AGEs up-regulate RAGE and ER expression at the protein and transcript levels in MCF-7 cells, in a RAGE-dependent manner after blockade of AGEs/RAGE interaction using neutralizing anti-RAGE antibody. Throughout the study, BSA had no effect on cellular processes. These findings pave the way for future studies investigating whether the exposure of AGEs-treated ER-positive breast cancer cells to estrogen could lead to a potentiation of the breast cancer development and progression.
Sabine Matou-Nasri, research scientist at King Abdullah Medical Research Center (KAIMRC), is leading the Cell and Gene Therapy group, part of Medical Genomics Research Department. She obtained her PhD degree in Biological and Medical Engineering in first class honors with distinction at University of Paris 13, Paris, France. She had her post-doctoral training at the School of Healthcare Science, Manchester Metropolitan University, Manchester, United Kingdom.
During her PhD and first post-doctoral training, she established structure-function relationships of sulfated polysaccharides (extracted from brown seaweeds) endowed with anticoagulant, antithrombotic and pro-angiogenic properties. She ended up with an international patent.
Since she has been at KAIMRC, her work is focused on various medical fields related to cancer (lymphoma, leukemia, and breast cancer), diabetes, inflammatory disease (gastritis) and infectious diseases (MERS-CoV). Her main aim is to pinpoint cancer-specific biomarkers and to investigate the anticancer effects of phytochemical compounds.
She has been active in research with 32 peer-reviewed publications in Biochimica and Biophysica Acta, Scientific Reports for instance, and several research grants as a principal investigator and as a co-investigator. She has also co-supervised and supervised 8 MSc, 5 PhD students, and 1 postdoctoral fellow.
- Islamic Azad University, Iran
- Title:Synthesis of Chitosan-Grafted-Poly(N-vinylcaprolactam) Coated on the Thiolated Gold Nanoparticles Surface for Controlled Release of Cisplatin
- Time :
The gold nanoparticles surface was modified by thioglycolic acid ligand and their surface was coated by the chitosan-grafted-poly(N-vinylcaprolactam) (chitosan-g-PNVCL) copolymer. The cisplatin anticancer drug was loaded into the synthesized nanocarriers and its performance was investigated for the treatment of MCF-7 breast cancer cells in vitro. The lower critical solution temperature (LCST) of PNVCL/chitosan and PNVCL/chitosan coated gold nanoparticles were found to be 38 and 39°C, respectively. The cisplatin loading efficiency, cisplatin release from nanoparticles at different temperatures and pH values as well as the pharmacokinetic studies were examined. The maximum cisplatin release from nanoparticles was achieved at T>LCST (42 °C) and pH of 5. The Korsemeyer-Peppas model was best described the cisplatin release from nanoparticles. The maximum MCF cell death was found to be 92% using cisplatin loaded gold/TGA/chitosan-g-PNVCL nanoparticles under an induction heating system.
I received my PhD in organic chemistry in 2003. Since then I have been a faculty member at central branch of Azad University in Tehran/Iran. My team and I successfully performed several research projects in synthesis and application of magnetic and non magnetic nanoparticles as suitable adsorbents with an acceptable potential for coating with smart polymers and perform controlled absorption and release of drugs, especially anti cancer drugs. The results of these projects have been published, presented at international congresses or patented. My current research focuses on the synthesis and application of polymeric nano carriers, which are able to controlled absorption and release of the anticancer drugs in different conditions.