34^th Euro-Global Summit on Cancer Therapy & Radiation Oncology July 25-27, 2019 | Park Inn by Radisson Hotel & Conference Centre London Heathrow Bath Road Heathrow Middlesex UB70DU

Biography:

Dr Mari Aparici is a Clinical Professor at Stanford University. She is a Nuclear Molecular Physician with residencies in both Europe (Barcelona) and US (Stanford), and with Molecular imaging fellowships from Stanford University. She is a physician-scientist in the development of Molecular Imaging. She has more than 20 years of clinical and research experience in the field, more than 10 years of a leadership position as Chief Nuclear Medicine at the San Francisco VAMC as part of her prior appointment as a UCSF faculty member, and now as Head of the Theranostics and Nuclear Therapies program at Stanford University. She has published more than 100 papers in reputed journals, has been serving as an editorial board member of reputed journals, has been PI of NIH and non-NIH grants and serves as a member of several to committees at her University and several Societies. as her expertise in evaluation and passion in improving the health and wellbeing. Her open and contextual evaluation model based on responsive constructivists creates new pathways for improving healthcare. She has built this model after years of experience in research, evaluation, teaching and administration both in hospital and education institutions. The foundation is based on fourth generation evaluation (Guba& Lincoln, 1989) which is a methodology that utilizes the previous generations of evaluation: measurement, description and judgment. It allows for value-pluralism. This approach is responsive to all stakeholders and has a different way of focusing.

Abstract:

The clinical management of lesions suspicious for malignancy relies not only on diagnosis of benign versus malignant potential but also tumor grading, immunohistochemical and genetic information. Pathological analysis remains the gold standard for definite diagnosis. Hence, a carefully performed biopsy with low risk of complication is crucial. Compared to open biopsy, image-guided biopsies are minimally invasive and confer several advantages including low morbidity, low complication rate and cost savings. FDG-PET/CT has shown higher diagnostic accuracy than conventional imaging CT in characterizing tumor in initial staging, treatment response evaluation and follow-up. PET/CT guided biopsies may allow early histologic diagnosis and staging before morphologic changes are evident. PET/CT biopsy can therefore rule out/in malignancy in early stage of disease and re-stage different types of cancer. Non-real-time PET/CT biopsies have used the image co-registration of a prior PET with an intraprocedural CT. However, this method is inaccurate in time and space, takes long time and requires special software. The aim of this study is to report the initial experience of utilizing the real-time intraprocedural PET/CT guided biopsies, including feasibility and technical requirements.  

Biography:

Olivier E Pardo has completed his Graduation from the Faculty of Pharmacy Paris-V, France where he was awarded a Doctorate in Industrial Pharmacy in 1997; PhD in Biochemistry and Molecular Biology at Imperial College-London in 2002 and Post-doctoral experience in the laboratory of Prof. Julian Downward at the CRUK-London Research Institute where he worked on the regulation of apoptotic cell death and cell migration. He created the Cellular Regulatory Networks lab at Imperial College, Department of Surgery and Cancer in 2006. His team focuses on understanding the molecular mechanisms underlying chemo-resistance and metastasis in lung and other cancers.

 

Abstract:

Lung cancer is the commonest cancer killer worldwide. Tyrosine-kinase inhibitors (TKI) are novel agents in the treatment of this cancer. However, their efficacy is impaired by the rapid development of drug-resistance. Here, we discuss resistance to the first-generation EGFR inhibitors (eg. Erlotinib and SRC inhibitors eg. Dasatinib). The principal mechanism of resistance to first-generation EGFR inhibitors is the appearance of the T790M receptor mutation. Our metabolomics analysis revealed that resistance is associated with decreased cellular levels of glutathione (GSH), a direct consequence of the T790M mutation. This occurred because of decreased SQSTM1/NRF2-mediated transcription of GSH synthesizing enzymes in cell lines and clinical samples with T790M-EGFR. Increasing GSH levels in resistant cells re-sensitizes these to first-generation EGFR inhibitors in vitro and in vivo. As clinically-relevant compounds exist to achieve this, our finding may have profound therapeutic and economic consequences. Src family kinases (SFK) are commonly over-expressed/hyperactivated in lung cancer. However, despite their on-target efficacy, SRC inhibitors have failed to prevent tumour growth and improve patients’ survival in multiple clinical trials. Here we show that this failure is associated with the induction of autophagy in treated cells that prevents these compounds from triggering apoptosis. Targeting autophagy, either genetically or using our novel small-molecule inhibitor, C1A, sensitizes lung cancer cell lines to Dasatinib both in vitro and in vivo by unlocking the apoptotic response. These findings propose new combinational therapeutic strategies that could resurrect the use of SRC inhibitors in the treatment of lung cancer.

Biography:

Olivier E Pardo has completed his Graduation from the Faculty of Pharmacy Paris-V, France where he was awarded a Doctorate in Industrial Pharmacy in 1997; PhD in Biochemistry and Molecular Biology at Imperial College-London in 2002 and Post-doctoral experience in the laboratory of Prof. Julian Downward at the CRUK-London Research Institute where he worked on the regulation of apoptotic cell death and cell migration. He created the Cellular Regulatory Networks lab at Imperial College, Department of Surgery and Cancer in 2006. His team focuses on understanding the molecular mechanisms underlying chemo-resistance and metastasis in lung and other cancers.

Abstract:

Lung cancer is the commonest cancer killer worldwide. Tyrosine-kinase inhibitors (TKI) are novel agents in the treatment of this cancer. However, their efficacy is impaired by the rapid development of drug-resistance. Here, we discuss resistance to the first-generation EGFR inhibitors (eg. Erlotinib and SRC inhibitors eg. Dasatinib). The principal mechanism of resistance to first-generation EGFR inhibitors is the appearance of the T790M receptor mutation. Our metabolomics analysis revealed that resistance is associated with decreased cellular levels of glutathione (GSH), a direct consequence of the T790M mutation. This occurred because of decreased SQSTM1/NRF2-mediated transcription of GSH synthesizing enzymes in cell lines and clinical samples with T790M-EGFR. Increasing GSH levels in resistant cells re-sensitizes these to first-generation EGFR inhibitors in vitro and in vivo. As clinically-relevant compounds exist to achieve this, our finding may have profound therapeutic and economic consequences. Src family kinases (SFK) are commonly over-expressed/hyperactivated in lung cancer. However, despite their on-target efficacy, SRC inhibitors have failed to prevent tumour growth and improve patients’ survival in multiple clinical trials. Here we show that this failure is associated with the induction of autophagy in treated cells that prevents these compounds from triggering apoptosis. Targeting autophagy, either genetically or using our novel small-molecule inhibitor, C1A, sensitizes lung cancer cell lines to Dasatinib both in vitro and in vivo by unlocking the apoptotic response. These findings propose new combinational therapeutic strategies that could resurrect the use of SRC inhibitors in the treatment of lung cancer.

Biography:

Dr. Mallinath G has done his MBBS from Mysore Medical College, Mysore University, and Karnataka, India and pursued his MS in Orthopaedic All India Institute of Medical Sciences [AIIMS]. He had done his fellowship in Joint Replacement from AIIMS. Currently he is a Senior Consultant Orthopedic Surgeon in Manipal Hospitals Bangalore. His areas of Interest are Knee Surgery, Hip Surgery, knee and shoulder Arthroscopy. Experienced in Spine surgery and Arthroscopy and also has an experience of 4 years in teaching for both the Undergraduates and Postgraduates at AIIMS.

 

Abstract:

Introduction: Achilles tendon is the strongest and thickest tendon in the human body, which takes its name Achilles, from Homer’s Iliad. Incidence rate of these ruptures range from 6 to 18 per 100000 populations. Several operative and nonoperative treatment options are available. Operative repair of Achilles tendon ruptures leads to improved early outcomes, in terms of length, strength, functional activities and reduced tendon elongation compared to non-operative treatment.

Operative methods include percutaneous, mini-open and open Achilles repair. Open repairs carry an increased risk of wound healing problems, whereas minimally invasive techniques are reported to have an increased risk of iatrogenic nerve injury.

Materials & Methods: Twenty patients with acute closed traumatic Tendo-Achilles rupture were operated using above mentioned technique between January 2010 to June 2017 in Bangalore out of which 15 were males and 5 were females. Patient was put on anterior below knee slab in plantar fl exion of the foot for 2 weeks followed by walking below knee cast for 4 weeks. Patients were followed up at 6 weeks, 3 months, 6 months and 1 year following surgery and complications if any were observed. Postoperative AOFAS ankle-hind foot score was taken at last follow up.

Results: Percutaneous Tendo-Achilles repair has a good outcome in 90% of the cases. Th ere were two cases with complications. One case was with surgical site infection at one of the puncture sites and the other was sural nerve hypoesthesia. Th e average AOFAS score was 89% (76-92) in which 65% (13) were considered excellent, 25% (5) were considered good and 10% (02) were considered fair outcome. Th ere were no re-ruptures.

Discussions: Th ere have been many advances in percutaneous and mini open repairs of Tendo-Achilles tear to reduce the risk of complications. In the technique described here, distal bony fi xation is achieved with the use of suture anchors reducing the number of suture-tendon interfaces which in turn reduces the chance of failure. Th e study also discusses about the risks and methods to avoid iatrogenic nerve injury and measure the outcome using AOFAS ankle-hind foot score at one year follow up.

Conclusion: We present our technique of percutaneous Tendo-Achilles repair which has minimal wound and nerve injury complications and early return to activities with a good functional outcome.