Euro Oncology Summit October 18-19, 2018 | Amsterdam, Netherlands

Biography:

Dr Ola A.Harb has completed her  PhD from Zagazig University, Zagazig, Egypt. He is the Head of the department of Ptahology, Faculty of medicine. He has published more than 30 papers in reputed journals and has been attend more than 20 conference as a speaker

Abstract:

Background: Cyclooxygenase-2 (COX-2), play an important role in inflammation and  carcinogenesis. Cyclin D1 plays a vital role in cancer cell cycle progression. The activity of cyclin D1 can be blocked by CDK inhibitors, including p21 (cyclin-dependent kinase inhibitor-1A, CDKN1A, CIP1) that plays a role in regulating cell cycle.

The purpose of this study was to evaluate expression of COX-2, Cyclin D1 and P21 in colorectal cancer patients, analyze the relationship between their expression and the prognosis of patients.

.Methods: expressions of Cox-2, Cyclin D1 and P21were evaluated in 60 paraffin blocks colorectal cancer patients that were followed up for 3 years. The relationship between their level of expressions and prognosis of patients was analyzed.

Results: Cox-2& Cyclin D high expression was positively correlated with higher grade and Duke stage (P=0.000). P21 high expression was negatively correlated with higher grade (p=0.002), presence of distant metastasis and advanced Duke Stage (P=0.001). Cox-2& Cyclin D1 over expression and P21 low expression were associated with higher incidence of tumor recurrence (P=0.04, 0.000 respectively), higher incidence of cancer specific death (p=0.002, 0.004&0.000 respectively) but no significant correlation with response to therapy with all markers.

Conclusion: High levels of expression of Cox-2 & Cyclin D1 are markers of poor prognosis, while high level of expression of P21 is a marker of good prognosis in colon cancer patients

Keywords: Cox-2, Cyclin D1, P21, colon cancer patients, immunohistochemistry, prognosis

Biography:

Dr Nelson has a broad background in training in radiation oncology and palliative care and clinical oncology. She is currently a PGY-II internal medicine resident at the Sinai Hospital of Baltimore and is interested in pursuing a medical oncology fellowship.

Abstract:

Introduction: Myasthenia gravis is an autoimmune neuromuscular disorder traditionally seen in bimodal distribution in young women in their 20s-30s or older men in their 60s-70s. Discovery of immunotherapy has brought immense hope in survival outcomes for patients with malignant melanoma, lung, renal and head/neck cancers but it also opens Pandora’s box of immune-related toxicities for which early recognition and appropriate clinical management are paramount. Here we describe a case of immunotherapy induced myasthenia gravis de novo.

Case: A 77-year-old man with HPV+ stage IVA squamous cell carcinoma of the tongue presented with sudden onset orthopnea and dyspnea on exertion for the past day.  One week ago, he received his second cycle of nivolumab as part of his neoadjuvant therapy. He was seen at an outside hospital and was found to be acute hypercapnic respiratory failure and placed on BiPAP. Additionally, he was started on empiric treatment for community-acquired pneumonia with levofloxacin and doxycycline and transferred to a tertiary care center for further management. On further evaluation, he endorsed diplopia, blurry vision, fluctuating muscle weakness that is worse at the end of the day, change in voice and proximal muscle weakness. His exam was consistent with bilateral ptosis, weak hip flexion and shoulder abduction, positive sniff test and poor vital capacity and negative inspiratory force values suggestive of impending respiratory and diaphragmatic failure secondary to myasthenic crisis. He was admitted to the ICU and placed on BiPAP and frequent NIF and VC monitoring. He was started on pyridostigmine but showed no clinical improvement on day 1 and hence was initiated on plasmapheresis from day 2 for a total of 10 days. Investigations showed positivity of Ach-R modulating and binding and blocking antibodies with negative voltage gated calcium channel antibodies. EMG revealed decrement of the compound muscle action potential in the repetitive stimulation test indicative of myasthenia gravis. He responded well to the above treatment and underwent successful left partial glossectomy and weaned off mechanical ventilation and has  been cancer free so far. He is doing well on maintenance prednisone and pyridostigmine.

Discussion: Literature review show that there is a significant 30.4% MG-specific-related mortality due to immunotherapy alone which this case demonstrates the importance of vigilance and early detection for effective treatment and management as the era of immunotherapy dawns.    

Biography:

Dr. Manisha has completed her PhD from Central Drug Research Institute, Lucknow, India. She is currently working as a post-doctoral fellow under the government SERB-NPDF fellowship program at the school of Biotechnology, at JNU, New Delhi. She also worked as a post-doctoral fellow at Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden. She has published 11 papers in reputed journals.

Abstract:

Background: Epidermal growth factor receptor (EGFR) inhibitor gefitinib (Iressa) is a synthetic anilinoquinazoline, which is extensively used for treating non small cell lung cancer. Apart from its anti-cancer activities against several cancers, gefitinib was also reported to show MAPK dependent anti-leukemic effects in EGFR-deficient acute myeloid leukemia (AML) cell line HL-60 and patients. However, it is still unclear to how gefitinib induces these effects in cells that lacks its target. Therefore our aim was to decipher the underlying mechanism of action of gefitinib in AML cells. Gefitinib was found to reduce intracellular cyclic AMP and induce cytostatic effects in EGFR-rich and EGFR-deficient cell lines both. As a next logical step, a GPCR profiling study was done that revealed that gefitinib regulates a number of GPCRs. However, the radioligand competition and functional assays suggested that gefitinib inhibits histamine receptors. This was further confirmed by the activation of histamine receptors by pharmacological agonists followed by assessment of gefitinib mediated effects in AML cells, which suggested that histamine receptor inhibition is necessary for gefitinib mediated effects in AML cells. The co-immunoprecipitation studies also validated the interaction of EGFR and Histamine receptor 4.  In the end we concluded that our results indicate the involvement of histamine receptors in gefitinib mediated EGFR-independent anti-proliferative effects. Thus our report provides new insights into gefitinib mode of action, and also indicates that other EGFR inhibitors displaying anti-leukemic properties may display similar signaling attributes and can contribute towards gefitinib related non-targeted response.

Biography:

Abstract:

Introduction:

Syndecan-2(Sdc-2) is a transmembrane heparin sulphate proteoglycan that is upregulated in breast tumours. Preliminary data indicates that overexpression of Sdc2 peptides in BCC’s increases their migratory and immunosuppressive properties. Sdc-2 fragments were designed and cloned into a vector to mimic a component of endogenous Sdc-2. Overexpression of TGF-β results in pro-tumorigenic modifications to cells in the tumour microenvironment. Therefore, inhibition of the TGF-β pathway would be a rational approach in breast cancer therapies. Our objective was to determine the role of Sdc-2 on the TGF-β pathway in MDA-MB-231 BCC’s.

Method:

Cultured MDA-MB-231 breast cancer cells were transfected with Fc empty vector, Sdc-F1 or Sdc-F2. A serum starvation and a TGF-β3 time course were carried out. RNA was harvested from the cells at 0, 1, 2, 4, 6 after TGF- β3 treatment. The RNA was purified and quantified, followed by cDNA synthesis via reverse transcription. qPCR was carried out to determine the effect of Sdc-2 fragments on TGF-β induced genes such as SMAd7, Serpine1 and CTGF.

Results:

Promising data was collected from all three experiments, however due to sensitivity of qPCR the figures were different preventing statistical significance. Throughout all three experiments consistent trends were observed such as SMAD7 and Serpine1 downregulation by Sdc-2-Fc-peptides indicating TGF-β suppression especially at the 6 hour time point.

Conclusions:

Further investigation of Sdc-2-Fc-peptides is imperative since data collected revealed Sdc-2 interaction with TGF-β induced genes.

References:

1. Lim H, Multhaupt H, Couchman J. Cell surface heparan sulfate proteoglycans control adhesion and invasion of breast carcinoma cells. 2016.
2. Chen L, Klass C, Woods A. Syndecan-2 Regulates Transforming Growth       Factor-  Signaling. 2016.

Biography:

Bruno de Paula has completed his Clinical Oncology formation in NCI-Brazil. He works as Oncology Researcher and Staff in Breast Cancer Hospital at NCI-Brazil, a prestigious mixed assistency and research organization. He is a young oncologist with experience in Phase 1 clinical trials acquired in a Fellowship in Cambridge Reseach Institute UK.

Abstract:

Cardiotoxicity (TC) is the most concerning side effect of Trastuzumab. It remains unclear whether the current arbitrary recommendations provide an adequate balance between preventing heart damage and curtailing a curative treatment. The main objective of this study was to determine the incidence rate and consequences of CT during (neo) adjuvant trastuzumab treatment in a real-world scenario.
Methods: Retrospective analysis of cardiac monitoring during trastuzumab-based neo- and adjuvant breast cancer treatment at a large public medical hospital.
Results: 409 breast cancer patients were treated with (neo)adjuvant-based trastuzumab between 2011 and 2014. The median age was 52 years and the body mass index (BMI) 27.54 kg/m2. The mean number of echo/patient was 5. (Figure 1) Although none of these patients were symptomatic, all of them had their treatment delayed due to the echo findings. Twenty-eight patients (75.6%) recovered their cardiac function and 9 (24.4%) had trastuzumab suspended. There were 14 deaths (6.3%) in the studied sample, being 1 (0.2%) attributed to late CE (4 years after treatment). (Figure 2)
Conclusion: Frequent monitoring of cardiac function during (neo)-adjuvant treatment was associated with 9% asymptomatic CE, mirroring large adjuvant trials results. Despite being transient, LVEF drop lead to frequent treatment delays and occasional suspensions. It remains unclear whether LVEF decline is predictive of late CE and at the same time whether treatment efficacy is compromised. A prospective study is needed to assess the optimal way to monitor which will probably implicate in better allocation of resources.

Biography:

My self, Julie Chessell, mom and registered nurse from Ontario, Canada. My personal interest focuses on pediatric hepatoblastoma, Liver organ transplantation and mindset. I have spoke on behalf of the Canadian Liver Foundation as well as the Organ Project. Our journey has been featured on TSN, SportsNet, The Ottawa Senators, The Organ Project and various news outlets.

Abstract:

In an instant life can change. In a moment, a family can be shattered and what they thought was their norm becomes their most challenging experience. It can either tear families apart or bring them closer. You become a victim or a survivor. Pediatric Gastrointestinal Cancer, or more specifically Hepatoblastoma, is a diagnosis typically found in 0-4 years of age, not in an eleven year old. How do parents view this devastating news? A dream is shattered, and how you handle this frightening information can impact not only your patient, the extended family and but most certainly parental mental capacity. Choosing to succumb is not an option. Selecting to change your mindset for the positive can have a profound impact on treatment and overall outcome. No one care plan is the same. No one is exempt, whether you are in the healthcare arena or not.  It takes a village of people to have a hand in allowing a child not to become a statistic.  Pediatric Cancer can potentially be a lifelong medical condition, with Hepatoblastoma accounting for only 1% of pediatric cancers. Supporting families and their journey is key to overall health. Hope is that beautiful place between the way things were and the path of the way things are yet to be. There comes a point in life when you realize that nothing will ever be the same. You realize that from that point on, time will be divided into two parts – before this and after this.  Our journey is different than the next, but with the passion to give back, anything is possible. Empowering people about determination and resiliency is key. Now it’s our turn to make that difference!!

Biography:

MOHAMMED HASSAN is currently a Masters of Sciencec (MSc) student in Biotechnology at the University of the Western Cape (UWC), South Africa. Prior to his MSc, he completed his Honours and his thesis focused on developing of gentyping system for pharmacogenomics profiling cholesterol lowering drugs In 2016, Hassan completed his biotechnology Bachelor of Science (cum laude) at Omdurman Islamic University, Sudan. Hassan is a recipient of the Golden Key International Award, 2017. Hassan's current researcher within the Bioinformatics research group (BRG) in  the Biotechnology department focuses on genetic biomarkers using computational methods. Genetics biomarkers in breast cancer treatment is the key to fight the multidrug resistance in chemotherapy treatment. ABC transporter genes as genetic biomarkers are crucial receptors for an effective management of chemotherapy resistance of breast cancer patients being treated with tamoxifen. Therefore, there is a need to understand the genetic diversity of ABC transporters in different populations so that we can give Tamoxifen to the right population group. The chairperson of the group is Dr. Ashley Pretorius. Dr. A. Pretorius is serving as the chairperson of the science faculty assessment committee as well as senate for the same committee he is also serving as Deputy Director at Mintek, NRF funding review panel member, MRC funding review panel member. Him and Dr. Marius they are working together on project for HIV/ADIS and Prostate cancer treatments.

Abstract:

Breast cancer is the most common and invasive solid tumour occurring in women across the world, with 1.67 million new cases reported in 2012, resulting to 324,000 deaths in South Africa (WHO, 2012). The rate of breast cancer patients has highly increased as well as the survival rate. This is due to the improvement of cancer treatments and usage of new technology. Tamoxifen has been widely used for the treatment of breast cancer patient around the world. Previous studies have shown that Tamoxifen is a substrate for ATP-binding cassette transporter proteins (ABC) drug transporters. However, ABC drug transporters in breast cancer treatment with Tamoxifen appears to be associated with poor clinical outcomes insome population groups, thus resistance developed to this medication by these peoples. It demonstrates that ABC transporters are crucial receptors for an effective management of chemotherapy resistance of breast cancer patients being treated with tamoxifen. Therefore, there is a need to understand the genetic diversity of ABC transporters in different populations so that we can give Tamoxifen to the right population group. In this study, we focus on profiling the ABC drug transporters associeted to Tamoxifen resistance and characterise their role in breast cancer treatment poor prognosis, mortality rate and the survival rates using in-silico methods.SurvExpess and Kaplan Meier plot (KM plot) as a bioinformatics tools used for survival analysis in this study to test whether ABC transporters down-regulated or up-regulated after using the chemotherapy treatment. KM plot is freely accessbile database used to study the survival analysis. Therefore, a certain criteria was set to study the reoccurrence free survival (RFS) rate for breast cancer patients. Restrictions for all patients were set as default for all (ER, PR, HER2, lymph node, intrinsic subtype, and TP53 status). Quality control was checked to remove redundant samples and to exclude the biased arrays and the proportional hazard assumption was zero and not selected. Survival analysis ran for number of 3166 samples. Result obtained was showing up-regulation for ABCB10 gene expression and the reoccurrence free survival analysis was calculated by P value of 0.00016. In conclusion, the high expression of ABC genes associated with effluxing of Tamoxifen leading to ineffective therapeutic intervention in breast cancer leading to poor prognosis as well as poor survival rate and increased mortality rates. Gene therapy and gene splicing of ABC transporters it would be possible to down-regulate the gene expression of ABC genes in post treatment thus would be possibility of blocking ABC genes from effluxing of neither chemotherapy nor developing multidrug resistance to chemotherapy.

Biography:

Ravat has completed his MD from Mahidol University. He is Medical Oncologist of  Faculty of Medicine, Ramathibodi Hospital, Mahidol University. He is interested in hepatocellular carcinoma research.

Abstract:

Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the ninth in women, as well as the second leading cause of cancer-related death globally. Almost 50% of all cases of HCC are associated with chronic infection with hepatitis B virus (HBV). Serum hepatitis B surface Antigen (HBsAg) is an important diagnostic marker of HBV infection. This study aimed to investigate relationships between serum HBsAg and intrahepatic HBsAg in HBV-associated HCC. Serum HBsAg was detected by chemiluminescent microparticle immunoassay. Intrahepatic HBsAg was determined by immunohistochemistry (IHC) in formalin fixed paraffin embedded (FFPE) tissues (matched non-cancerous and HCC tissues) from 88 patients, whose serum HBsAg was positive in 56 patients (63.64%). In serum HBsAg-positive group, intrahepatic HBsAg was positive-staining in 73.2% of non-cancerous tissues, but only in 10.7% of HCC tissues. Significant correlation between serum HBsAg and intrahepatic HBsAg was observed in non-cancerous tissues (p<0.001), but not in HCC tissues (p=0.415). We concluded that intrahepatic HBsAg in HBV-associated HCC tissues was detected by IHC at significantly lower frequency than in non-cancerous tissues. This warrants further investigation into other biomarker(s) of HBV infection in HBV-associated HCC tissues, which might provide more information for insight into the development and progression of HBV-associated HCC.

Biography:

Abstract:

Introduction:

Lung cancer sometimes can mimic or present as non-resolving pneumonia. Patients usually present with pneumonia like symptoms not resolving over course of 1-2 weeks despite being treated with antibiotics.

Case:

43-year-old female with an active smoking history of 20 years presented to us with complaints of fever, cough, fatigue, headache, and shortness of breath. One month prior to presentation, she traveled by car for 2 days after spending 2 months in Louisiana. She was recently seen at an outside hospital with similar complaints, where she was treated with a 10-day course of amoxicillin-clavulanate for presumed community acquired pneumonia.

On presentation, patient's vitals were BP 127/87, Pulse 117, Temp 38C, and Oxygen saturation 88%.

On examination, she was noted to have decreased breath sounds on the right lower lung and swelling of the left leg.

Pertinent labs included an elevated white blood cell count (13.4), eosinophils (790), and D-dimer (27,529).

Due to concerns for PE, CT thorax was done, which showed extensive multifocal consolidation of the right and left lungs, mediastinal lymphadenopathy, bilateral pleural effusions more pronounced on the right side, and pericardial effusion. A small PE was also noted on left side. Leg Duplex showed an acute DVT of the left leg.

The patient was started on IV Heparin for the acute DVT and PE. Per pulmonology recommendation, she was started on antibiotics for suspected severe multi-focal community-acquired pneumonia.

She proved refractory to antibiotic treatment. Subsequent work-up for atypical pneumonia included cold agglutinin titer/Mycoplasma titers, Q fever, Chlamydia titers 1:64, Strongyloides, Histoplasma, Fungitell, Cryptococcus, and HIV. All were negative.

Cardiac surgery and pulmonary team were consulted. Patient had pericardial window drained and pleural pig-tail placed. Bronchoscopy was also done. Fluid cytology was positive for adenocarcinoma of lung. Further imaging studies revealed metastases to the brain , left adrenal gland and sacral spine.

Discussion:

Patients presenting with pneumonia like symptoms and not improving despite treatment with antibiotics should undergo further work up to rule out other causes including lung cancer.

High clinical suspicion is required for the early diagnosis as delayed diagnosis can lead to poor prognosis.

Biography:

Dr Ola A.Harb has completed her  PhD from Zagazig University, Zagazig, Egypt. He is the Head of the department of Ptahology, Faculty of medicine. He has published more than 30 papers in reputed journals and has been attend more than 20 conference as a speaker

Abstract:

Background;

Recent research is focusing on discovering novel effective targets for therapy of advanced and metastatic cervical cancer. Ezrin that is encoded by EZR gene is an Ezrin/Radixin/Moesin (ERM) family member. Ezrin is a linking protein of the cell membrane and the cytoskeleton that mediates the connection between both of them. E-cadherin is a calcium-dependent glycoprotein which is found in normal epithelial cells. It could mediate cell adhesion.The relation between the expression of Ezrin and E-cad and relations between other clinical and pathological features in cervical cancer patients has not been sufficiently clarified.

Aim of this research was to evaluate Ezrin and E-cadherin expression in cervical cancers patients, to correlate such expression with pathological and clinical data of the patients, to explore their values in cancer progression and prognosis of cervical cancer patients.

Methods; We have assessed Ezrin and E-cadherin expressions in sections from 55 paraffin blocks of cervical cancer, we have followed our patients for 3 years then we correlate expression of both markers with clinic pathological criteria, cancer progression, relapse and  survival rates.

Results; Ezrin over expression and E-cadherin down regulation were associated with higher grade, advanced FIGO stage, (p<0.001), presence of distant metastases (p=0.003), poor therapy response, higher relapse rate (p<0.001) and poor DFS& OS rates (p<0.001).

Conclusion; Ezrin over expression is associated with down regulation of E-cadherin and were related to more invasiveness liability, relapse after successive therapy and poor prognosis in patients with cervical cancer.

Key words; cervical cancer, Ezrin, E-cadherin, relapse, progression, survival

Biography:

An Inspiring life-sciences professional, Abilesh has a decade of experience in Medical informatics. Developed a keen interest in Personalized medicine, Cancer Genomics, drug discovery and earned his Masters degree in Medical informatics from the University of Manchester. He has been working on the technologies to personalize cancer treatments post his studies and went on to start this venture. He also worked on several bioinformatics methodologies and has identified a platform for effective cancer treatment. Abilesh is a go-getter and a creative soul wandering to explore new opportunities.

Abstract:

On a busy day, there was a call from an oncologist asking how our CANLYTx could help a CA endometrium first line therapy treatment negative female patient Mrs. Grace, aged 43 years.

A regular first line therapy with a combination of Platin, Doxorubicin and Paclitaxel was administered post diagnosis. Mrs. Grace was soon given the bad news that she had to undergo further chemotherapy with different chemo agents (chosen by trial and error) after a regular scan was done indicating progression of the tumor.

Two scenarios had risen due to the progression of Tumor for Mrs. Grace and it was at this stage we received the call from her doctor asking about our CANLYTx.

Now, we would like to demonstrate the extraordinary proficiency of whole exome sequencing with CANLYTx in such situations.

The process began with harvesting the DNA from the FFPE tumour block obtained from the diagnostic biopsy sample to perform whole exome assay. The resulting interpretation from this process revealed mutation in ABCB1 gene suggesting the use of Doxorubicin caused reduced drug clearance and hence addition of Imatinib along with the platins, doxorubicin and Paclitaxel would prove effective. Our CANLYTx platform recommends the use of Imatinib as it sensitizes endometrial cancer cells to Platins by targeting CD-117-positive-growth-competent cells and the platin resistance gene were not mutated. In addition, molecular simulation studies were carried out on the above combination to further validate the use of these agents. Our molecular simulation platform calculates a dock score using the concept of binding energy minimization between the agent and the target, the target being the mutant gene or its coding protein.

The database indicates that PARP inhibitors would be ineffective due to the absence of mutations in the associated genes. A routine targeted therapy targeting EGFR, BRAF gene would be ineffective due to the absence of protein coding mutations in the genes.

Next steps for the patient is the follow up for development of additional resistance mutations in the existing genes or newer genes by way of liquid biopsy from circulating tumour DNA or any other NGS technology beyond just testing for limited genes.

Note: This is a tentative program and subjected to change time to time basing on the confirmation of speakers.