25^th Global Meet on
Cancer Research & Oncology

Dr. Kubecek is a graduate of Charles University, Faculty of Medicine in Hradec Kralove, Czech Republic. He has been practicing since 2012 as the medical oncolo-gist at the Department of Oncology and Radiotherapy at the Hradec Kralove University Hospital. He focuses on the treatment of GI cancers, malignant melanoma, and ovarian cancer. In 2016, Kubecek worked as a research scholar at the Department of Experimental Medicine and Pathology at Mayo Clinic, Rochester, USA. As a PhD student, he is currently working on a research project dedicated to the use of extracorporeal elimination of pegylated liposomal doxorubicin to improve the treatment tolerability in patients with ovarian cancer.

Statement of the Problem: Pegylated liposomal doxorubicin (PLD), a formulation of doxorubicin hydrochloride encapsulated in polyeth-yleneglycol-coated liposomes, has proved its efficacy in the treat-ment of ovarian cancer and other solid tumors. The major dose-limiting toxicities include hand-foot syndrome (HFS) and mucositis. Thanks to the unique pharmacokinetic properties of PLD and the de-fective vasculature of the tumor tissue, the peak PLD concentration in the tumor is attained considerably faster than in other tissues in which toxic reactions occur. Interestingly, less than 5% of the administered dose is delivered to the target tissue; hence, it is believed that the majority of the administered PLD has a limited therapeutic value and is merely responsible for organ toxicity. Therefore, the extracorpo-real removal of circulating PLD could be a promising method to in-crease PLD tolerability while preserving its antitumor activity. This study seeks to evaluate the safety and efficacy of PF and the related changes in chemotherapy-related toxicity. Methodology & Theoreti-cal Orientation: Patients with platinum-resistant ovarian cancer were treated with PLD 50 mg/m2 in one-hour IV infusion q4w, followed by plasma filtration (PF) performed at hours 44(46)-47(49) post dose. Plasma PLD concentration was measured to assess the pharmacoki-netic parameters and PF efficacy. Treatment-related toxicity and the patients’ outcome were also evaluated. Findings: Fifteen patients were enrolled in this study and received a median of 3 (2-6) chemo-therapy cycles. In all, 53 PF cycles were evaluated. PF eliminated a median of 30.1% (12.7-64.6%) of the administered PLD dose. Only one case of grade 3 HFS and grade 1 mucositis were documented. Conclusion & Significance: Plasma filtration represents a potent method in the removal of circulating PLD. It is well tolerated and it seemingly reduces the incidence of hand-foot syndrome and mucosi-tis.

Dr Zhumakayeva works at Medical University of Karaganda as 1-year doctoral student of the Oncology Department. Education (university and graduation year): Karaganda State Medical University, 2015. Faculty: General Medicine. Specialization, postgraduate education: oncologist, radiodiagnosis, including ultrasound, CT, MRI, X-ray. Work experience in the specialty: over 3 years. Academic degree and title: Master of Medical Sciences. Scientific works, copyright certificates: 9 publications, 1 certificate of state registration of the object of intellectual property.

Introduction. The problem of breast cancer (BC) is one of the important and complicated in oncology. In this aspect, there is a significant amount of interest in the study of oxidative processes, since their disorders can act as one of the pathogenetic factors of carcinogenesis. Aim of the study. To study the Reactive carbonyl compounds of proteins (RCCs) in plasma and in erythrocytes of blood of the BC patients after surgical treatment. Materials and methods. The blood of 20 women with BC was examined, which have I-IIIa stages after surgical treatment in the volume of radical resection or radical mastectomy performed at the first stage of treatment. The control group consisted of practically healthy women (n = 15). The level RCCs in erythrocytes and in blood plasma was determined by the method of Levine R.L et al. (1990). Results of the study. In erythrocytes of BC patients with I stage, there was a slight decrease in the percentage of RCCs. At the same time, an increase of RCCs was observed in II stage BC patients (by 50% compared to control, p <0.05). The level of RCCs in erythrocytes of BC patient’s blood with III stage was 2 times lower than the control. In blood plasma of BC patients with I stage the significant increase in RCCs was observed (3 times compared with the control). In BC patients with II stage, this indicator exceeded control by 70-75% (p <0.05), whereas in patients with III stage of BC, the content of RCCs did not differ significantly from control. Conclusions. These data suggest the development of carbonyl stress in the body of BC patients. Surgical removal of the tumor in breast cancer does not eliminate the conditions for the oxidative modification of proteins.

Dr holds a PhD in Biology from the Instituto de Biologia Experimental e Tecnológica, Portugal. From 2002 to 2008 she worked as Post-Doctoral fellow in the Instituto Gulbenkian de Ciência, Portugal, on projects that contributed to the understanding how HO1-1 protein affords cytoprotective and anti-inflammatory effects in various diseases. After that, she developed research in cancer. First on the role of HDAC inhibitors on hematologic malignancies and then on the mechanisms by which p16 protein exerts anti-oncogenic effects in osteosarcoma and on the mechanisms underlying the stromal fibroblast transformation in breast cancer. Since 2014, she has been a scientist at Instituto de Biologia Experimental e Tecnológica, Portugal, where she works on projects in the fields of biopharmaceutical process development and oncology. Her main scientific interests relates to the mechanisms underlying cancer development and therapy.

Background: Breast cancer (BC) is the most common cancer in women and has a high rate of relapse and death. The Notch signaling pathway plays an important role in normal breast development and homeostasis. Dysregulation of Notch receptors and its ligands Jagged1, Jagged2, and DLL4 has been detected in BC and implicated in tumor development, progression, drug resistance, and recurrence. The Notch ligand DLL1 has emerged as a player in BC as its expression is undetectable in normal breast tissues, but moderate to high in BC. In this study, we examined the role of DLL1 in BC luminal A MCF-7 cells. Methodology: DLL1 siRNA and recombinant DLL1 protein were used to evaluate the effects of DLL1 in MCF-7 cells. Gene expression was analyzed by qRT-PCR and immunobloting. Cell growth and proliferation were assessed by trypan blue exclusion and the MTT methods. Microscopy and scratch wound-healing assays were used to evaluate colony formation and cell migration. Findings: In MCF-7 cells, DLL1 downregulation reduced proliferation, colony formation efficiency, and migration. On the other hand, treatment with recombinant DLL1, which activates the Notch signaling pathway, increased MCF-7 cell proliferation and migration, confirming that DLL1 contributes to these processes in these luminal A BC cells. Conclusion: These findings provide evidence that DLL1 contributes to the pro-carcinogenic effects of luminal A MCF-7 cells by promoting clonogenic growth, cell proliferation, and migration.

I’m graduated from Capital Medical University in 2015 as the major of Medical Laboratory Tests (MLT). After finished the internship in Beijing Anzhen Hospital, I joined in Dept. Clinical Oncology, HKU as research in October 2015. In September 2017, I began my postgraduate study in the same laboratory with supervision of Prof. Dora Kwong and Prof. XY Guan. Our laboratory is focus on discovering novel cancer related genes and mir-RNAs in gastric cancer (GC), hepatocellular carcinomas (HCC), esophageal carcinomas (ESCC) and nasopharyngeal carcinoma (NPC). My current study is supported by Health and Medical Research Fund (No.04150826).

Hepatocellular carcinoma (HCC) is the fourth most common type of cancer in Hong Kong SAR and ranks as third leading mortality rate of cancer type worldwide. A wise strategy for better understanding the enrolled molecular mechanisms in HCC progression, which is needed to discover novel diagnostic markers and therapeutic targets. According to analysis our RNA sequence data of three paired HCC and non-tumor tissue samples, human maelstrom (MAEL) gene was chosen to study. Our preliminary data suggested that MAEL frequently upregulated in HCC patients, associated with tumor size, adjacent organ invasion, tumor recurrence and worse overall survival rate. Previous study demonstrated that MAEL promoted HCC cells proliferation and metastasis as well as upregulating several stemness related genes expression in mRNA level through AKT/GSK3β/Snail signaling pathways. However, the cancer stemness regulating ability and downstream targets of MAEL are still not well studied. Therefore, this project would focus on revealing novel targets of MAEL and further investigate the unique role in regulating cancer stemness. We analyzed MAEL expression and survival data in TCGA LIHC cohort, the results were consistent with our previous findings. We found that overexpress MAEL could not only promote the ability of HCC cell proliferation and mobility in vitro, but also increase the proportion of CD133+ cells, self-renew and sorafenib resistant ability. Moreover, knockout MAEL showed reverse results in PLC8024 cell line inhibited these functions. We applied next generation sequencing (NGS) technology to compare with vector group and MAEL transfected group cells which revealed that MAEL enrolled in extracellular matrix (ECM) receptor interaction pathways mediated cancer stem cell marker CD44 expression. This finding confirmed by Q-PCR, western blots and flow cytometry. Taken together, these data suggest MAEL could promote HCC cells proliferation, metastasis as well as increasing stem cell features.

Dovile Zilenaite is a medical geneticist at the National Center of Pathology, Affiliate of VULSK and a doctoral student at Vilnius University Faculty of Medicine. Her research focuses on the development and standardization of multiple IHC procedures for multiparametric and spatial analysis, digital image analysis and prognostic modelling in the breast cancer patients. Main scientific interests: genetics, cancer biology, immunology, digital analysis and analytics of whole slide pathology images to describe heterogeneity of tumor cell population and microenvironment

Statement of the Problem: Tumour infiltrating lymphocytes (TIL) are associated with better prognosis in triple-negative and HER2-positive breast cancer (1, 2), and TIL assessment by digital image analysis (DIA) has been successfully implemented in colorectal and other cancers (3). However, results in hormone receptor-positive breast cancer (HRBC) based on manual scoring remain contradictory (2). Here we used an automated DIA method to extract prognostic value of novel Immunogradient indicators in CD8+ cell density profiles in HRBC. Methodology & Theoretical Orientation: Surgically excised HRBC samples from 102 patients were immunohistochemically stained for CD8, digitized and analysed by the HALO™ platform. The DIA data was subsampled by a hexagonal grid and explicit rules were then used to extract the tumour-stroma interface zone (IZ) and compute novel Immunogradient indicators from TIL density profiles across the IZ. The prognostic value was evaluated by survival analysis. Findings: The IZ Immunogradient indicators (mean CD8+ density in the tumour aspect of the IZ, Immunodrop, Centre of Mass) allowed prognostic stratification of patients in univariate analyses (hazard ratios: 0.21 (p=0.0002), 2.79 (p=0.0140), and 0.28 (p=0.0044), respectively). The best and independent indicator of better OS by multiple Cox regression model (hazard ratio: 0.23 (p=0.0007)) was an aggregated Immunogradient factor (Agg. Factor), obtained by the sum of two factor scores (CD8+ density and “gradient towards the tumour”). Remarkably, the aggregated Immunogradient factor revealed a striking drop of patients’ survival probability 5 years after surgery. Conclusion & Significance: The Immunogradient indicator for CD8+ cell density is an independent predictor of better OS in HRBC patients with the particular diversion of OS 5 years after the surgery.

Biography Dr. Yeoh is an Associate Attending in the Department of Anesthesiology and Critical Care Medicine at Memorial Sloan Kettering Cancer Center in New York. She is a member of the department’s Quality Assurance Committee and her research interests include patient safety, outcomes and performance, and technology in the field of anesthesiology. Her recent publications have focused on real-time locating systems and its effects on the efficiency of anesthesiologists in the perioperative setting.

Case: A 57 year old female with a history of uterine and breast cancer s/p chemoradiation presented for cervical LEEP/cone biopsy/D&C. Her medical history was complicated by elevated LFTs with recent hyperhomocysteinemia (> 50micromol/l, normal 4-15). She was seen by a hematologist prior to surgery, and it was concluded that elevated homocysteine levels were due to cancer therapy and alcohol consumption. The procedure was performed under monitored sedation, with 2mg of Midazolam, 50mcg of Fentanyl, and a bolus of 70mg of Propofol followed by a steady infusion of 150mcg/kg/min. Discussion: Causes of hyperhomocysteinemia include genetic predisposition, acquired deficiencies (folate, B6, B12), malignancies, and renal disease. Elevated homocysteine levels result in thromboembolic complications by causing endothelial dysfunction, increasing procoagulant activity, and decreasing antithrombotic effect. Challenges of patients with hyperhomocysteinemia undergoing anesthesia are related mainly to the procoagulant state and efforts should be focused on thromboprophylaxis and maintenance of hemodynamics and euvolemia. Nitrous oxide should be avoided as it inhibits methionine synthase and can further increase homocysteine levels. Patients with co-morbidities that include coronary artery disease, peripheral vascular disease, and cerebrovascular disease are at increased risk for peri-operative thrombotic events. This risk is amplified for high-risk procedures under general anesthesia. Conclusion: In this case, the patient presented for a low-risk procedure. She did not have a history of coronary or cerebrovascular disease, but had risk factors (surgery, age>50yrs, malignancy, cancer therapy) in addition to a hypercoagulable state (due to elevated homocysteine levels) that posed increased peri-operative risk for thrombotic events such as deep venous thrombosis and pulmonary embolus. The decision was made to proceed with monitored sedation over general anesthesia so as to avoid fluctuations in hemodynamics and decrease the risk of venous stasis. The procedure took approximately 45 minutes and the patient recovered uneventfully and was discharged home the same day.

Ausrine Nestarenkaite works as a medical geneticist at the National Center of Pathology and is a doctoral student at Vilnius University, Institute of Biosciences, in Lithuania. She focuses on the multiparametric and spatial analysis of tumour microenvironment components in digital microscopy slides. Main scientific interests: molecular genetics of colorectal cancer, cancer immunology, and digital pathology applications.

Statement of the Problem: The immune response within the tumour microenvironment assessment methods were proposed to predict patient survival and therapy outcomes in colorectal (CRC) and other cancers; nevertheless, automated operator-independent approaches are lacking. We present a new image analysis method to automatically extract Immunogradient indicators and their prognostic value in CRC patients. Methodology & Theoretical Orientation: Surgically excised CRC samples from 101 patients were stained for CD8, scanned, and analyzed by Indica labs HALOTM software. The image analysis data was then subsampled by a hexagonal grid which was used to extract and rank the tumour interface zone (IZ) according to distance to the tumour edge. Lastly, a set of novel Immunogradient indicators representing CD8 cell density profiles across the IZ were computed. The prognostic value of the indicators was tested by univariate and multiple survival statistics. Findings: The Immunogradient indicators ImmunoDrop (ID) and Centre of Mass (CM) for the CD8 cells, as well as CD8 cell densities within tumour and stroma aspects of the IZ and their factor scores provided significant stratifications of CRC patients into prognostic groups (p<0.05). Multiple Cox regression analyses of extracted indicators along with conventional clinicopathologic characteristics revealed ID and the Aggregated IZ CD8 cell response factor as strong independent predictors of worse (HR: 2.41, p=0.0126) and better (HR: 0.41, p=0.0196) 5-year overall survival, respectively. Conclusion & Significance: The proposed automated, data-driven digital image analysis method for the IZ immune infiltrate assessment provides strong independent prognostic biomarkers of anti-tumour immune response in CRC. The method is operator-independent and is based on single CD8 immunohistochemistry slides.

Nina Giulia Sautter graduated from Ludwig-Maximilians Universität in Summer 2018 in the field of Dentistry. She is passionately interested in improvement of life quality of cancer patients. In 2016 she started her thesis about the importance of physical exercise and nutrition as a part of treatment in gastrointestinal cancer patients. The results of her research show a significant impact on the patient’s survival.

BACKGROUND: Gastrointestinal cancer patients are particularly predisposed to develop cancer cachexia. Cachectic patients are characterized by loss of adipose tissue as well as skeletal muscle wasting which has a tremendous impact on quality of life and survival (1, 4). In terms of improvement for this multifactorial syndrome, Klinikum rechts der Isar (MRI) in Munich, Germany has founded NECC, a treatment concept including nutrition intervention and an individual training program. METHODS: In this study we focused on patients with pancreatic (n = 15) and upper gastrointestinal cancer (n = 21). Body composition using CT images was analyzed initially, 4 weeks, 3 months and 6 months after initial visit of NECC (Image 1). To underline the outcome, NECC patients were matched to adequate partners who correspond in age, gender, diagnosis with TNM classification and type of surgery. The control group does not receive any further support concerning nutrition and physical exercise. RESULTS: Our study demonstrates that NECC has impact on overall survival (Image 2). Skeletal muscle mass index (SMAI) was higher 4 weeks and 3 months after initial visit in NECC patients compared to control group. Intramuscular adipose tissue index (IMATI) was higher after 6 months in NECC patients compared to controls. CONCLUSION: The NECC program influences overall survival in patients with gastrointestinal cancer. This effect was significant in patients with pancreatic cancer but not in patients with upper GI cancer. Additionally, we observed effects of NECC on SMAI 4 weeks and 3 months after initial visit and on IMATI 6 months after initial visit. The promising results should be further investigated in randomized studies.