Day1

Abstract:
Emerging reports suggest Delta-like-ligand 4 (DLL4) is a promising target to augment the effects of VEGF inhibitors. Simultaneous blockade of VEGF/VEGFR and DLL4/Notch signaling pathways leads to more potent inhibition of tumor progression by a synergic anti-angiogenic activity in various mouse xenograft models. We have developed a bispecific antibody targeting VEGF and DLL4 (ABL001, TR009) with similar in vitro biological and biochemical activities compared to each monoclonal antibody, e.g., binding affinities on each target, competitive inhibition abilities on ligand-receptor interactions, and inhibition effects on endothelial cell proliferation and DLL4-induced Notch1-dependent activation. In addition, ABL001 more efficiently inhibited the tumor progression of several cancer cell line derived xenograft models as well as patient-derived xenograft models than an anti-VEGF antibody or anti-DLL4 antibody alone. Currently the safety and tolerability of ABL001 are evaluating in clinical phase 1 trial (ClinicalTrials.gov Identifier: NCT03292783). In conclusion, ABL001 is being developed as a promising therapeutic bispecific antibody for cancer treatment.

Biography:
Dr.Weon-Kyoo You received his PhD majored in Biochemistry at Yonsei University in 2004. Then, he worked as a postdoctoral fellow at UC San Francisco, and as a researcher at Sanford-Burnham Prebys Medical Discovery Institute from 2004 to 2012. He successfully performed several research projects and published many peer-reviewed papers in the field of tumor-induced angiogenesis and tumor microenvironments. After he came back to Korea, he joined at the Hanwha Chemical, R&D center as a principal research scientist to discover and develop a novel bispecific antibody until March, 2016. Currently he is working as the R&D Head at a startup biotech company, ABL Bio, Inc. and leading new antibody-based drug development projects.

Abstract:
Bispecific antibodies that interact with tumor antigens on cancer cells and activating receptors on immune cells offer an innovative immunotherapy approach. REGN4018 is a bispecific antibody that binds both Mucin 16 (MUC16), a glycoprotein that is highly expressed on ovarian cancer cells, and CD3, thus bridging MUC16-expressing cells with CD3+ T cells. REGN4018 induced T cell activation and killing of MUC16-expressing tumor cells in vitro. In preclinical studies with human ovarian cancer cells and human T cells in immunodeficient mice, REGN4018 potently inhibited growth of intraperitoneal ovarian tumors. Moreover, in a genetically engineered immunocompetent mouse expressing human CD3 and human MUC16 [humanized target (HuT) mice], REGN4018 inhibited growth of murine tumors expressing human MUC16, and combination with an anti– PD-1 antibody enhanced this efficacy. Immuno-PET imaging demonstrated localization of REGN4018 in MUC16-expressing tumors and in T cell–rich organs such as the spleen and lymph nodes. Toxicology studies in cynomolgus monkeys showed minimal and transient increases in serum cytokines and C-reactive protein after REGN4018 administration, with no overt toxicity. Collectively, these data demonstrate potent antitumor activity and good tolerability of REGN4018, supporting clinical evaluation of REGN4018 in patients with MUC16-expressing advanced ovarian cancer.

Biography:
Dr.Alison Crawford is a Senior Staff Scientist in the department of Oncology and Angiogenesis at Regeneron Pharmaceuticals, Inc. She completed her BSc in Immunology from Glasgow University before being admitted to the Wellcome Trust Ph.D. program at Edinburgh University where she focused on T cell memory. Her post-doctoral work at the University of Pennsylvania examined T cell exhaustion during chronic viral infection and the role of checkpoint inhibition in alleviating T cell exhaustion. This piqued her interest in immunotherapies and she made the transition into industry at Regeneron Pharmaceuticals where her group uses pre-clinical models to examine bispecific antibodies targeting solid tumors. She led the in vivo pre-clinical research efforts on REGN4018 (MUC16xCD3) to advance the antibody through to IND submission.

Abstract:
The Her receptor tyrosine kinase family has four members, namely Her-1 (EGFR or ErB1), Her-2 (Neu or ErbB2), Her-3 (ErB3) and Her-4 (ErB4). Activation of the kinases results in intracellular signalling events leading to some oncogenic and aggressive behaviour of cancer cells including those involved in cell growth, apoptosis and cellular migration and invasiveness. Known downstream signalling events include activation of the Ras, PI3K, MAPK pathways. Clinically, the levels of the Her family members have been shown to be aberrantly expressed in various tumour types including breast cancer and lung cancer. Mutations of the coding genes for the family members have also been found in solid cancers and have been key indicators for the choice and success of anti-Her treatments. Our team has been investigating the relationship between the Her family gene expression levels and the clinical outcomes of patients with breast, gastric, pancreatic and lung cancers and exploring the prospects and potential mechanisms of targeting Her kinases in the intervention of metastatic diseases from these cancers in particular in their bone and brain metastases. Significant correlations were found between the expression levels of selective members of the Her family and the overall as well as disease free survivals in these cancer types. Using cancer cell models, brain endothelial cell models and in vitro ‘metastasis’ models, combined with protein kinase platform technologies, we further explored the prospect of specific and broad spectrum inhibitors to the Her kinases on the invasive and metastatic behaviour of cancer cells. We have identified that certain broad spectrum Her kinase inhibitors, for example Nerlynx, have some profound effects on the bone and brain metastatic properties of cancer cells and also impact on the permeability of brain endothelial cells. Together with the clinical cohort results, our protein kinase platform assays have also identified patterns of responsive signalling events that may contribute to the anti-metastatic properties of the Her kinase inhibitors. In summary, our studies on the expression of the Her family kinases in clinical cancer cohorts together with laboratory investigation have shown that targeting certain Her family kinases are highly useful when treating metastatic cancers including those metastasised to bone and brain. We have also identified patterns of responsive signalling events that may allow prediction of the likelihood in patient’s response to the anti-Her treatment.

Biography:
Professor Wen G. Jiang is a Professor of Surgery and Tumour Biology at Cardiff Medical School of Cardiff University. He is currently the Director of Cardiff’s China Medical Research Collaborative (CCMRC) and Cardiff University Dean of International. Professor Jiang’s research interest is the molecular and cellular basis of cancer invasion and metastasis and development of anti-metastasis treatment.

Abstract:
Enhancing therapy sensitivity is a big challenge in oncology. Based on genetic and epigenetic modifications altering intra- and extracellular processes, glioblastoma (GBM) belongs to the group of tumor entities with unmet need, is highly refractory to therapy and associated with poor clinical outcome. Novel effective treatment approaches are urgently required. Here, we found the collagen type-I receptors discoidin domain receptor 1 (DDR1) and beta1 integrin overexpressed in GBM. We identified a critical function of the promitotic and adhesion-mediating DDR1 in altering GBM treatment resistance. In a large number of GBM cultures and clinical samples, we show a DDR1 and GBM stem cell marker co-expression that correlates with patient outcome. We exhibit DDR1 inhibition in combination with radiochemotherapy using temozolomide in GBM models to enhance sensitivity and prolong survival to a degree superior to conventional therapy. We further identify a 14-3-3-Beclin-1-Akt1 protein complex assembling with DDR1. This protein complex is required for prosurvival Akt and mTOR signaling and the regulation of autophagy-associated therapy sensitivity. Our results uncover a mechanism driven by DDR1 that controls GBM therapy resistance via autophagy and suggest DDR1 as a rationale target for the development of therapy-sensitizing agents.

Biography:
Dr. Nils Cordes graduated from Medical School of the University Erlangen-Nürnberg, Germany, in 1998. Subsequently, he worked as resident in radiation oncology at the Universities Erlangen-Nürnberg and Tübingen before he took on a position as radiobiologist at the Institute of Radiobiology of the German Army. His studies on cell-matrix interactions pioneered the field by untangling the role of the cancer cell adhesion resistome. In 2010, he became Full Professor of Radiobiology at the Technische Universität Dresden, and Head of Radiobiology of OncoRay and the Department of Radiobiology, Institute of Radiooncology, Helmholtz Center Dresden-Rossendorf. Based on Dr. Cordes´ research, our understanding of how cancer cells resist therapy by adhesion to extracellular matrix or neighboring cells has essentially increased. By using more physiological, matrix-based 3D cell cultures, it become obvious that the physiological environment mediates a tremendous impact on signal transduction, gene expression, chromatin organization and adaptation mechanisms induced by therapy.

Abstract:
Background: Radical prostatectomy, a standard management approach for localized Prostate Cancer (PC), may cause a stress response associated with immune modulating
effects. Regional anesthesia was hypothesized to reduce the immune effects of surgery by minimizing the neuroendocrine surgical stress response, thus mitigating tumor cells dissemination. Our primary objective was to investigate whether the use of spinal
blocks attenuates PC tumor cells dissemination on an animal model. We also assessed the number of circulating NK cells and the amount of inflammatory and anti-inflammatory cytokines.
Materials and methods: A subcutaneous tumor model, with PC-3M cell line transfected with a luciferase-producing gene (PC-3M-luc-C6) was used. After proper tumor establishment and before tumors became metastatic, animals were submitted to tumor excision surgeries under general or combined (general and spinal) anesthesia. A control group was only anesthetized with general anesthesia.
Results: The subcutaneous tumor model with PC-3M-luc-C6 cells was effective in
causing distant metastasis after 35 days. The number of circulating tumor cells increased in animals that underwent surgery under general anesthesia alone compared to the group submitted to combined anesthesia. Interleukin 6 levels were different in all groups, with increase in the general anesthesia group.
Conclusion: Our results suggest that combination of spinal and general anesthesia may attenuate the suppression of innate tumor immunity and it might be related to a reduction in the neuroendocrine response to surgery.

Biography:

Dr. Gustavo Inoue obtained his medical degree from University of Sao Paulo Medical School and completed his residency in anesthesiology at Hospital das Clinicas of Sao Paulo (HCFMUSP). He currently works as anesthetist at private hospitals in Brazil and is a research fellow at University of Sao Paulo Medical School.
Dr. Inoue’s research interests mainly involve studying the influence of anesthesia techniques
on cancer recurrence after surgery.

Abstract:
Background: Colonic stenting has emerged as preferred palliative treatment for left sided malignant obstructions. It shortens hospital stays, decreases healthcare cost, reduces permanent stoma rates, and expedites the start of chemotherapy. The role of stenting as a bridge-to-surgery remains unsettled.
Data source: For this discussion the recommendations of the American and European society of gastroenterology and colorectal surgery were reviewed. We will discuss the benefits and risks of stenting in palliative setting and as bridge-to-surgery. Quality of life, hospital stay, and health care cost will also be considered.
Conclusion: Non-traversable colon masses during endoscopy are considered a risk factor of development of intestinal obstruction but preventive stent placement in patients without obstructive symptoms is not recommended. The risk of technical or clinical failure is significant at 25%. If stent placement allows neoadjuvant chemotherapy, it may increase the rate of R0 resections. Perforations may raise local recurrence and mortality rates.

Abstract:
This discussion covers changes in the provision of cancer genetic testing and screening in the United States since the passage of the 2010 Patient Protection and Affordable Care Act (ACA), with a focus on benefits for the marginalized. Similar reforms have been undertaken in European countries, e.g., federal subsidies combined with insurance carrier plan flexibility in Switzerland, and Germany’s offering of different healthcare options for low- and high-income individuals. In the United States, the uninsured rate dropped from 16.1% before the ACA’s passage to 9.6% in 2021. Medical claims databases (N > 50,000 women, both affected and unaffected) noted distinct increases in BRCA1/2 testing rates, e.g., up 68% from 2012 to 2014, the first year the state insurance Exchanges opened. BRCA1/2 test ordering cancellation rates due to a medical geneticist / genetic counselor authorization requirement were most pronounced for African American and Latino subscribers, however. From 2012 to 2015, annual colorectal cancer screening rates increased 1.29 per 1,200 Latino, and 0.58 per 100 non-Latino adults. However, as of 2016, the odds ratios for Lynch syndrome (hereditary nonpolyposis colorectal cancer) germline genetic testing for colorectal tumors were 0.65 for Latinos and 0.39 for African Americans compared to whites. Expansion of the Medicaid program covering low-income Americans has been beneficial to rural populations; impact on colorectal cancer screening rates for racial-ethnic minorities has been mixed.
Incorporation of policy recommendations from other professionally recognized sources beyond the U.S. Preventive Services Task Force – the National Comprehensive Cancer Network, Evaluation of Genomic Applications in Practice and Prevention (EGAPP), and Healthy People 2030 – needs to be considered in enlarging the ACA coverage criteria for hereditary breast and ovarian cancer and Lynch syndrome genetic testing and counseling. When addressing the needs of population groups, especially the underserved, progress in the adoption of clinical policy and governmental reform are complementary. Instances of recent state-level reform, e.g., refinement in criteria for Medicaid coverage of BRCA1/2 testing; continued expansion of state Medicaid programs; and the controversial adoption of Medicaid block grants by one state will be covered. The talk will conclude with the recent presidential proposal to develop fast-track testing to detect multiple cancer types simultaneously and to coordinate screenings with cancer treatment centers nationally – the cancer “moonshot” program.

Biography:
Stephen M. Modell, M.D., M.S. has been the Research and Dissemination Activities Director of the Center for Public Health and Community Genomics at the University of Michigan School of Public Health since 2001. The Center promotes the integration of genomic discoveries into public health practice utilizing community input. Prior to his current position, he was research director in genetics policy for the Department of Health Management and Policy, University of Michigan School of Public Health. He has co-taught the Health Management and Policy course “Issues in Public Health Genetics” for more than 15 years, a course that links issues to policy for new and established genetic technologies. Dr. Modell served as chair of the American Public Health Association Genomics Forum Policy Committee from 2012-13. He was principal author of the 2013 APHA policy statement “Advancing Cancer Genomics in Public Health.” In 2021 he co-authored the chapter “Genetic Determinants of Health and Applications in Public Health and Preventive Medicine” for the 16th edition of Maxcy-Rosenau-Last Public Health & Preventive Medicine. Dr. Modell’s recent articles concern cancer genetic testing in marginalized groups in the context of healthcare reform, and cancer testing and screening for immigrant groups.

Abstract:
Acute lymphoblastic leukemia (ALL) and multiple myeloma (MM) are characterized by a monoclonal expansion of B- and/or T-cell lymphocyte progenitor/plasma cells, respectively. These diseases can be monitored by the detection of clonally rearranged immunoglobulin and/ or T-cell receptor genes, which are tumor specific and allow the detection of small numbers of malignant cells, so-called measurable residual disease (MRD). Detection of MRD to guide therapy has been a standard practice in treatment of (childhood) ALL for decades. In MM, a clear correlation is found between absence of MRD and longer survival. Quantitative allele-specific oligonucleotide (qASO)-PCR is the current gold standard molecular method for MRD detection in these hematologic malignant tumors and has been standardized and performed in EuroMRD-approved laboratories all over Europe and beyond. However, this technique has some drawbacks: it is a labor-intensive technique that follows only two immunoglobulin and/or T-cell receptor gene rearrangements over time; clonal evolution can interfere with detection, possibly leading to false-negative results; false-positive results after stem cell transplantation have been reported; and the applicability of qASO-PCR in MM is limited to 50% to 70% of patients due to somatic hypermutation. However, these drawbacks can be overcome by next-generation sequencing (NGS). In this study, NGS is validated as an alternative method to qASO-PCR for MRD detection in both ALL and MM. The use of calibrators was a prerequisite for this comparison. These calibrators are composed of three different synthetic junctional regions per immunoglobulin and/or T-cell receptor locus and are added to the reaction mixture at a known amount. MRD results obtained by NGS and qASO-PCR were compared in 59 and 39 bone marrow samples of 33 and 14 patients with ALL and MM, respectively. Our results indicate that the use of gBlocks as calibrators makes the NGS approach a powerful tool to quantify MRD. With an input of 400 ng of DNA (corresponding to approximately 7E+04 cells), a limit of detection of 0.01% was achieved. The specificity of the NGS-MRD technique was 100%, and a correlation with qASO-PCR for quantifiable MRD results of 0.93/0.91 was found in ALL/MM, respectively. Especially for MM, the higher applicability (100%) of the NGS-MRD protocol, compared with qASO-PCR (57%), was clearly demonstrated. These results indicate that NGS-MRD is a reliable MRD detection method for more patients than the current gold standard qASO-PCR.

Biography:
Dr.Jona Van der Straeten graduated as Master in Biomedical Sciences in 2005 at the Vrije Universiteit Brussel (VUB). From 2005-2008 she worked in the research lab CYTO at the Department for Cell Biology and Histology at VUB. The focus of this research group is to gain better insights in the mechanisms of liver regeneration and the pathogenesis of liver fibrosis. Since 2008, she started working at the Molecular Hematology laboratory (Universitair Ziekenhuis Brussel) as scientific collaborator. This lab is the reference lab for MRD assessment in Belgium and is involved in many clinical studies like ALLTogether, Interfant, EsPhall, IntreALL for childhood ALL, and HOVON for adult ALL.

Abstract:
Lymphedema of upper limbs is a condition that usually arises after breast cancer treatment. The partial or total removal of axillary lymph nodes and the subsequent radiotherapy could lead to an incorrect discharge of lymph, which stagnates in the skin tissues by causing an incremental swelling of the whole arm, i.e. the lymphedema. The prevention and treatment of lymphedema is carried out in hospitals and rehabilitation centres through specific assessment methods based on the measure of the limb volume. These methods allow defining the severity of patient’s condition and permit to gather the measures for standard or custom orthopaedic stocking.
The presentation introduces a novel procedure based on ICT technologies for lymphedema assessment. The procedure is based on the 3D scanning of the arm and an ad-hoc developed application, named Lym 3DLab, which automatically computes linear and volumetric measurements starting from the arm virtual model. Acquired measurements can be also used to design the compression stockings for lymphedema treatment.
A validation test has been performed to compare the measurements computed by Lym 3DLab with both water displacement and circumference measurements, which are the most common methods for linear and volumetric measurement of a limb. Furthermore, a specific usability test has been performed to evaluate the 3D scanning procedure involving physiotherapists. The comparison between the volumes has highlighted how all the 3D acquired models have their volumes inside a range of acceptability. This range has been defined by considering the sensitivity error of the tape measure used to measure the water displacement. The comparison between the perimeters of cross sections computed with Lym 3DLab and the circumference measurements has shown results that are accurate with an average difference of 2 mm. The measure errors have been considered negligible by the medical personnel who evaluated the proposed procedure very promising. The test with physiotherapists has shown a high level of usability of the whole virtual environment, but the 3D scanning procedure requires an appropriate training of the personnel to make the 3D acquisition as fast and efficient as possible.
The achieved results and the physiotherapists’ feedback permit to plan a future test with patients affected by lymphedema in collaboration with the hospital and design orthopaedic compression stockings.

Biography:
Dr.Andrea Vitali is an Assistant Professor at University of Bergamo. Since 2012, he carried out research activities relative to the development of methods and computer-aided tools for the design of custom-fit products by integrating several technologies (e.g., CAD-CAE systems,motion capture systems, hand-tracking devices, 3D scanners and virtual reality). The deep knowledge of these technologies also allowed research activities to design innovative applications and web-platforms for rehabilitation processes of several categories of patients, such as patient with multiple sclerosis, spinal cord injured patients, patients with a brain stroke and patient affected by lymphedema. The research activities have been funded by several national and regional research projects in collaboration with public and private hospitals of Lombardy region.

Abstract:
Several alterations in the gastrointestinal tract which occur after appendectomy or cholecystectomy have been suggested to raise the risk of developing colorectal carcinoma. Given the frequency that these procedures are performed, we sought to determine whether a history of either cholecystectomy or appendectomy increased the risk of a future colorectal carcinoma. Firstly, we determined the number of patients with a history of appendectomy and cholecystectomy who developed colorectal carcinoma between January 2018 and February 2021, as well as the latency time between the two diseases. Secondly, we carried out a data-collection spanning 15 years after the primary surgery (January 2005 – December 2006). The post-cholecystectomy state is significantly more frequently observed in patients treated for colorectal carcinomas (both male and female), especially among those who developed right-sided or left-sided colon cancer, as opposed to anorectal cancer (p=0.53). However, the time elapsed between the two diseases is 20-25 years, which appears to be markedly long regarding such a multifactorial disease as the colorectal carcinoma. No similar extra risk was observed among patients having appendectomy. Secondly, we found no extra risk during the first 15 years after cholecystectomy. Although a statistically higher risk of colon cancer is observed after the removal of the gallbladder, but the latency time is long. Thus, cholecystectomy may not be an independent risk factor for colorectal carcinogenesis. Altogether, the patient is not exposed to a higher risk of colorectal carcinogenesis after having cholecystectomy.

Biography:
Dr.Miklós Mándi MD, PhD is working as a general surgeon and adjunct professor on the Surgery Unit of the Bajcsy-Zsilinszky Hopsital since 2008. He obtained the speciality in General Surgery in 2012. Parallel to his studies as General Surgeon he received the PhD degree in the same year in the field of Biochemistry for “Studies on Cyclophilin-D and NAADP on Ca2+-mediated events” on Semmelweis University. Nowadays, along with his clinical work, Miklós Mándi continues his scientific work in the field of Surgery. He has a wife and 2 children.

Abstract:
Pancreatic cancer is rarely diagnosed during pregnancy; it usually manifests with symptoms such as epigastric pain, vomiting, weight loss, and jaundice, rarely mimicking the hemolysis,elevated liver enzymes, and low platelet count syndrome. It has been postulated that there exists a correlation between the diagnosis of gestational diabetes mellitus and the occurrence of pancreatic cancer later in life. We conducted an expert literature review of the 31 available documented pancreatic cancer cases that were diagnosed during pregnancy. We also report pancreatic adenocarcinoma incidentally suspected in an asymptomatic woman affected by gestational diabetes mellitus; the woman was undergoing a fetal growth scan.

Abstract:
Aim: The main goal of this investigation was to evaluate the influence of positive beta haemolytic streptococci culture from the genital tract on patients receiving radiation therapy who suffer from cervical cancer. The other aim was to observe radiation therapy complica-tions.
Background: Group B streptococci (GBS), group C streptococci (GCS) and group G strepto-cocci (GGS) have been described as frequent invasive pathogens in elderly patients, often in association with underlying medical conditions including immunodeficiency and cancer.
Materials and methods: In the years 2006–2015, vaginal swabs from 452 patients were exam-ined. A total of 118 women with positive beta haemolytic streptococci (BHS) groups A, B, C, F, G cultures were analysed, of whom 111 were diagnosed with cervix cancer of IB to IVA degree according to the FIGO 1988 clinical classification.
Results: Of the 452 patients suffering from cervix cancer 26.1% were positive for A, B, C, F or G group BHS isolated from the genital tract. All of the 114 examined strains were sen-sitive to beta-lactam antibiotics. The antimicrobials for which resistance was noted were erythromycin, clindamycin, ciprofloxacin and tetracycline.
Conclusions: Positive cultures of BHS from the genital tract were demonstrated to occur in patients with cervix cancer. Complications were found during radiotherapy in 30 (27%) of these patients, including 20 (18%) patients suffering from clinical symptoms of inflamma-tion. When beta-lactam antibiotics are not recommended because of allergy, sensitivity tests to other drugs are necessary.

Abstract:
The long-term treatment with tamoxifen can alter the lipid profile of patients with breast cancer. Only a few studies associated the plasma concentrations of tamoxifen, endoxifen, and 4-hydroxytamoxifen with blood lipids, which is relevant as the distribution of these compounds for the tissues can be changed, negatively affecting the treatment. The variations in lipids also can account for the high interindividual variation in plasma concentrations of these compounds. The aim of this preliminary study was to associate the plasma levels of tamoxifen and the active metabolites with the lipid levels. An observational study of cases was conducted in patients with breast cancer using tamoxifen in a daily dose of 20 mg. The lipids were measured by spectrophotometric methods and the plasma concentrations of tamoxifen, endoxifen, and 4-hydroxytamoxifen by high-performance liquid chromatography. A total of 20 patients were included in the study. The median plasma concentrations of tamoxifen, 4- hydroxytamoxifen and endoxifen were 62 ng/mL, 1.04 ng/mL and 8.79 ng/mL. Triglycerides levels ranged from 59 to 352 mg/dL, total cholesterol from 157 to 321 mg/dL, LDL-c from 72 mg/dL to 176 mg/dL and HDL-C from 25.1 mg/dL to 62.8 mg/dL. There were no significant associations between the plasma concentrations of tamoxifen, 4-hydroxytamoxifen, and endoxifen with the levels of triglycerides and total cholesterol. The multivariate analysis revealed a weak association between plasma concentrations of tamoxifen and the active metabolites with HDL-c, LDL-c and VLDL-c. This finding provides preliminary evidence of the low impact of lipoproteins levels in the exposure to tamoxifen, 4-hydroxytamoxifen and endoxifen.

Biography:
Pharmaceutical-Biochemistry graduated from the Center for Higher Education of Pará (1995), Master in Biological Sciences-Neurosciences from the Federal University of Pará (2001) and Ph.D. candidate at the Postgraduate Program in Neuroscience and Cell Biology at the Federal University of Pará (2021) with a concentration area in Cell Biology. She is trained in Endocrine Physiology and has worked with research involving Atrial Natriuretic Peptide and basal secretion in an isolated atrium model. She develops studies with breast cancer patients in anticancer therapies, evaluating metabolic markers, visual and drug metabolism, focused on the quality of life and survival of patients. She currently holds the position of Adjunct Professor at the Faculty of Pharmaceutical Sciences of the Health Sciences Institute of the Federal University of Pará and has professional technical experience in Pharmaceutical Assistance in the Hospital and Clinical Pharmacy, Community Pharmacy and Clinical Analysis segments.

Abstract:
Photodynamic therapy (PDT) is a highly promising, clinically approved, and non-invasive treatment modality for several cancer types. A typical PDT action requires, light, tissue oxygen, and a photosensitizer (PS), which are combined to generate cytotoxic singlet oxygen (1O2). Among several challenges in the application of PDT, cancer cell selectivity is the most pronounced and substantial one, which is highly sought to minimize the severe side effects. In this direction activatable photosensitizers (aPS), which tend to stay inactive prior to activation with a tumor associated stimuli, have attracted great interest during last decades. We recently introduced an iodinated resorufin as a red-shifted, water soluble and photostable PS core, which can be also easily converted to an aPS by simply caging the phenolic moiety on the parent structure. To that end, we introduced first ever monoamine oxidase (MAO) activatable PDT agent (R1) based on an iodo-resorufin scaffold. R1 exhibited high 1O2 generation upon activation and induced selective photocytotoxicity towards MAO overexpressing SH-SY5Y neuroblastoma cells. Later, we converted iodo-resorufin core to a hydrogen peroxide (H2O2) responsive PS (RR1) and selectively killed MDA-MB-231 (breast) and HCT-166 (colon) cancer cell upon 595 nm LED irradiation. Additionally, the fluorescence signal of the resorufin core was restored after RR1 reacted with H2O2, suggesting that RR1 can function as a phototheranostic agent. Next, we showed that our parent PS core can be utilized as - galactosidase (β-gal) activatable PS (RB1), when the iodo-resorufin is caged with a sugar moiety. In-vitro cytotoxicity as well as the imaging studies showed that RB-1 induces selective photocytotoxicity towards U87 – glioblastoma cells with high β-gal activity and allows imaging of β-gal-positive cancer cells at the same time. Finally, it is worth to mention all resorufin-based aPSs showed negligible photocytotoxicity towards healthy cells. Our efforts to design new generation PS, which can be activated with different tumor-associated inputs, are in progress.

Biography:
Dr. Kolemen graduated from Chemistry Department at Bilkent University, Turkey in 2008,
where he also got his MSc degree two years later. Dr. Kolemen got his PhD at Bilkent University in 2014, where he trained as an organic chemist under the supervision of Prof. Engin Akkaya. Then, he dived into the field of chemical biology at UC Berkeley, Chemistry Department while working as a postdoctoral scholar in Prof. Christopher Chang’s lab. After joining Koç University, Turkey in 2017, Dr. Kolemen established the “Organic Chemistry and Chemical Biology” lab. In his independent career, he is combining his previous expertise to develop new generation tumor selective phototherapy drugs for cancer treatment and in vivo bio-imaging agents for cancer diagnosis. Dr. Kolemen has recently been awarded with a Science Academy BAGEP 2021 Award, which is given to outstanding young researchers in Turkey.

Abstract:
The lack of an effective treatment against cancer is not only due to its huge heterogeneity and complexity, but also to the fact that we do not entirely understand this disorder, highlighting the question of how cancer originates. Among the proposed models to explain the development of cancer, the hierarchical model has been widely accepted as a result of the extensive experimental data about the cancer stem cells (CSCs). Nevertheless, this model fails to explain several experimental observations such as the CSCs location mainly in the edges of solid tumour masses or the differences between primary and metastatic tumours. Moreover, increasing evidence shows that the CSC phenotype is not a rigid state and that it can be acquired by well-differentiated cancerous cells. In the present study, we present a critical review on the assumed tumour development models emphasizing the relevance of the dynamic and changing nature of malignant phenotype and the CSCs population in which the tumour microenvironment plays a crucial role. We also propose a new model of tumour origin and development that could have an impact on new therapeutic strategies.

Biography:
Dr. Pablo Hernández-Camarero Degree in Biochemistry. University of Granada, Spain (2011-2015), Master in Translational Research and Personalized Medicine. University of Granada, Spain (2015-2016),3rd PhD-student in the Department of Health Science, University of Jaén, Spain (2017).

Abstract

Background: Low-density neutrophils (LDN) have been shown to be increased in peripheral blood in patients with various diseases and closely related to immune-mediated pathology. However, the frequency and function of LDN in circulating blood of the patients following abdominal surgery have not been well understood.

Methods: LDN were determined by CD66b(+) cells, which were copurified with mononuclear cells by density gradient preparations of peripheral blood of surgical patients. The effects of the purified LDN on T cell proliferation and tumor cell lysis were examined in vitro. Neutrophil extracellular traps (NETs) production was examined by extracellular nuclear staining.

Results: The number of LDN with an immature phenotype is markedly increased in peripheral blood samples in patients after abdominal surgery. The frequency of LDN correlated positively with operative time and intraoperative blood loss. The purified LDN significantly suppressed the proliferation of autologous T cells stimulated with anti-CD3 mAb coated on plate and partially inhibited the cytotoxicity of lymphocytes activated with recombinant interleukin-2 against a human gastric cancer cell, OCUM-1. The LDN also produced NETs after short-term culture in vitro, which efficiently trap many OCUM-1. These results suggest that surgical stress recruits immunosuppressive LDN in the circulation in the early postoperative period.

Conclusions: The LDN may support the lodging of circulating tumor cells via NETs formation and inhibit T cell-mediated antitumor response in target organs, which may promote postoperative cancer metastases. Functional blockade of LDN might be an effective strategy to reduce tumor recurrence after abdominal surgery.

Abstract

Biliary tract cancers (BTCs) are a group of highly aggressive malignant tumors with a poor prognosis. The current diagnosis is based mainly on imaging and intraoperative exploration due to brush cytology havinga low sensitivity and the standard markers, such as carcinoembryonic antigen (CEA) and carbohydrate 19-9 (CA19-9), not having enough sensitivity nor specificity to be used in a differential diagnosis and early stage detection. Thus, better non-invasive methods that can distinguish between normal and pathological tissue are needed. MicroRNAs (miRNAs) are small, single-stranded non-coding RNA molecules of ~20-22 nucleotides that regulate relevant physiological mechanisms and can also be involved in carcinogenesis. Recent studies have demonstrated that miRNAs are detectable in multiple body fluids, showing great stability, either free or trapped in circulating microvesicles, such as exosomes. miRNAs are ideal biomarkers that may be used in screening and prognosis in biliary tract cancers, aiding also in the clinical decisions at different stages of cancer treatment. This review highlights the progress in the analysis of circulating miRNAs in serum, plasma and bile as potential diagnostic and prognostic markers of BTCs.

Abstract:
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.
Biography:
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.

Abstract:
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.

Abstract
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.

Biography
Dr. Sushreesangita P Behera, a doctoral candidate working under the supervision of Prof. Rajiv K Saxena at South Asian University, India. Her 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.

Abstract
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.

Biography:
Dr.Birgitte Federspiel – 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. Employments: 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 her country” employments, she have worked at various hospitals in Copenhagen. For the past 15 years she had worked at Copenhagen University Hospital in the dept. of GI pathology. She had dealt with CUP for the past nine years. Also she is part of the hospital’s Center of Excellence for neuroendocrine tumors. Her main focus of research is neuroendocrine tumors of the GI tract and the lungs and gastrointestinal pathology.

Abstract
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.

Biography
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.

Abstract:
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.

Biography:
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.

Research Field:
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.

Biography:
Dr.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.

Abstract:
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.

Biography:
Dr.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.

Abstract:
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.

Biography:
Dr. Edmyr R. Reis – 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 he work as a biomedical in the laser laboratory of Medicine and Surgery Experimental Center, Faculty of Medical Sciences, State University of Campinas, he has membership of the PanAmerican Society for Photodynamic Therapy (PAPDT). he had 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.

Abstract:
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.

Biography:
Dr. 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

Abstract:
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.

Biography:
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’.

Abstract
INTRODUCTION:
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.
CASE PRESENTATION:
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.
CONCLUSION:
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.

Biography:
Dr Amjad Shah , Specialist Acute care surgery of General surgery department , Hamad General Hospital , Doha , Qatar.

Abstract:
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.

Biography:
Dr.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.

Abstract:
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.

Biography:
Dr. Mahshid Nikpour Nezhati received her PhD in organic chemistry in 2003. Since then, she has been a faculty member at central branch of Azad University in Tehran/Iran. Her team and she 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.