Day 2 :
Medias Klinikum GmbH & Co KG, Germany
Keynote: Isolated Thoracic Perfusion with Chemofiltration (ITP-F) breaks through drug resistance in progressive and pretreated malignant pleural mesothelioma
Time : 09:40-10:15
Karl R Aigner is Medical Director of the Department of Surgical Oncology in Medias Klinikum Burghausen (Bavaria)/Germany. He had his surgical training in cardiovascular surgery at Friedrich-Alexander University in Erlangen. At Justus-Liebig University Giessen, he specialized in Surgical Oncology, focusing on vascular techniques of drug delivery such as Implant fix and Jet Port catheters, and in 1981 first performed a technique of isolated perfusion of the liver with heart-lung machine in man. Further on, he developed various techniques of segmental vascular isolation of body segments and organs, and the stopflow technique with adequately designed catheters. In 1982, together with Prof. Stephens from Sydney, he initiated the biannual International Congress of Regional Cancer Treatment (ICRCT) and from 1987 to 1991, he was president of the International Society for Regional Cancer Therapy. From 1985 to 1998, he was Managing Editor of the International Journal of Regional Cancer Treatment. He is author of numerous publications and book chapters, lectured and performed teaching operations nonvascular perfusion techniques and oncological surgery in Europe the United States and Asia.
Background: Survival of patients with progressive malignant pleural mesothelioma has not improved during the last decades. Treatment options are limited because of poor chemosensitivity of this disease and mostly non-operability due to advanced disease. We report on a phase II study on isolated thoracic perfusion (ITP) with subsequent chemofiltration (ITP-F) as arnlocoregional therapeutic strategy with increased drug exposure. Material & Methods: 28 patients with epitheloid mesothelioma were included in this study. 11 patients had prior surgical resection and all patients had prior Cisplatin and Pemetrexed based chemotherapy. Following multimodal therapy in allrnpatients, progress was revealed in CT-scan. No patient had abdominal, cerebral or bone metastases. Under general anesthesia, rna venous and arterial stopflow-balloon catheter was inserted via a femoral access and both blocked at the level of the diaphragm in vena cava and aorta. Chemotherapy consisting of 60 mg/m² Cisplatin and 15 mg/m² Mitoxantron was injected as pulsatilerninfusion against the aortic blood stream. After 15 minutes of ITP vascular blocks were released, followed by 45 minutes ofrnchemofiltration. Endpoints of the study were overall survival and quality of life. According to the protocol a minimum of fiverncycles each were administered.Results: Toxicity, due to chemofiltration was low with leucopenia and thrombocytopenia grade 1 in 11 patients and mucositisrngrade 2 in 6 patients. Surgical complications in terms of temporary lymph fistula in the groin occurred in 40 %. Gastrointestinal neurotoxicity was never observed. One year survival was 49%, 2 years survival was 31% and 3 years survival was 31%, 4 yearsrnsurvival was 23%. Median survival was 12 months.rnConclusion: ITP-F for pretreated patients with malignant pleural mesothelioma, progressive after multimodality therapy is arnvaluable treatment option with low side effects, offering a reasonable survival and maintaining quality of life.
DMB-Diagnostics GmbH, Germany
Keynote: New method of quantitative, circulating tumor cell (CTC) diagnostic, treatment selection, monitoring and surveillance with superior outcome for the patient
Time : 10:15-10:50
Martin Burow has completed his PhD in Chemistry and Biochemistry at the University of Münster in 1993 and worked 3 years as a Post-doctoral fellow for the Ministry of International Trade and Industry at the National Institute of Materials and Chemical Research (NIMC) in Tsukuba, Japan. After his return to Germany, rnhe started his career in the medical device industry and developed the Asian-Pacific markets for Brahms-Thermofisher in the field of medical diagnostics (thyroid, sepsis, prenatal and oncology). Later, he started his own company (DMB-Diagnostics GmbH) to introduce highly innovative diagnostics worldwide for better treatment standards for oncological patients.
Maintrac® is a laboratory based method to quantify in a reproducible manner living circulating tumor cells. This wayrnit is possible to do further analytic with these cells. Be it molecular genetic testing of certain tumor characteristics orrnsurface protein determination for real pharmaceutical target identification. Since these CTCs are alive, it is possible to checkrnall different chemot
Maintrac® is a laboratory based method to quantify in a reproducible manner living circulating tumour cells. This way it is possible to do further analytic with these cells. Be it molecular genetic testing of certain tumour characteristics or surface protein determination for real pharmaceutical target identification. Since these CTCs are alive, it is possible to checkrnall different chemotherapeutics and their killing rate on these CTCs. Best working medications can be selected before starting aggressive chemotherapies. Furthermore, it is possible to monitor treatment success “just” by quantifying CTC over the cause of the therapy. Even during and after endocrine therapy, it is possible to show how long to give i.e., Tamoxifen or when to switch to other, more efficient medication in case the cell number is increasing. This method was developed over the last decade and work on all tumours deriving from epithelial origin (almost all solid tumours). We showed in several clinical trials with >650 patients and >100,000 measurement significant improvement for patients and the overall relapse free survival while being monitored with this method. Maintrac® is nowadays already used in clinical routine in ~30 countries worldwide.
Therapeutics and their killing rate on these CTCs. Best working medications can be selected before startingrnaggressive chemotherapies. Furthermore, it is possible to monitor treatment success “just” by quantifying CTC over the causernof the therapy. Even during and after endocrine therapy, it is possible to show how long to give i.e., Tamoxifen or when to switchrnto other, more efficient medication in case the cell number is increasing. This method was developed over the last decade andrnwork on all tumors deriving from epithelial origin (almost all solid tumors). We showed in several clinical trials with >650rnpatients and >100,000 measurement significant improvement for patients and the overall relapse free survival while beingrnmonitored with this method. Maintrac® is nowadays already used in clinical routine in ~30 countries worldwide.
Elizabeth City State University, USA
Keynote: The role of tumor-associated macrophages (tams) and micro rna 146 alpha in cancer survival and efferocytosis in the tumor microenvironment
Time : 16:30-17:05
Hirendra Nath Banerjee received his BS with honours and MD degree from Calcutta University, India, MS in Molecular Biology from Conolly College of Pharmacy and Health Sciences at Long Island University, NY and Ph.D. in Molecular Biology from Howard University Cancer Centre, Washington, D.C. Dr.Banerjee did his post-doctoral training at Yale University Medical School and Medical University of South Carolina before joining Elizabeth City campus of the University of North Carolina where he is now a tenured Professor in the department of Natural, Pharmacy and Health Sciences. Dr.Banerjee did a sabbatical at Rockefeller University under the mentorship of Nobel laureate Dr.Gunter Blobel in studying the cell biology of nuclear pore complexes. Dr. Banerjee's current research involves cancer biology and Efferocytosis.
In this study, the role of the tumour microenvironment on cancer cell survival was analysed. The ability of cancer cells to inhibit nitric oxide production in macrophages and the increased drug resistance capabilities of the cancer cells in the presence of macrophages in the tumour microenvironment was explored. These recruited macrophages, also known as tumour-associated macrophages, appear to give the cancer cells drug resistance which can lead to failure in chemotherapy. The hypotheses were tested using Griess reagent systems to measure nitric oxide and trypan blue cell viability assays. The results showed a decrease in cancer cell death in the presence of macrophages when exposed to an anti-cancer drug cisplatin. Nitric oxide levels produced by cancer cells appeared lower when cultured with macrophages. MicroRNA-146a suppresses prostate cancer transformation from androgen-dependent to -independent cells, suppresses a kinase coding gene which reduces cell proliferation, invasion, and metastasis to human bone marrow endothelial cell monolayers, and is dysregulated by latent membrane protein 1 (LMP1) which contributes substantially to the oncogenic potential of Epstein-Barr virus. It is projected that microRNA-146a and other microRNAs may one day become biomarkers for clinical diagnosis and prognosis of several types of cancer including prostate. The miR-146a expression profile was investigated using novel African American and Caucasian prostate cell lines representing each pathological stage: benign, androgen dependent and independent tumours. Relative miRNA expression was determined by qRT-PCR, miRNA plate assay and smart flare technology after isolating total RNA from the cells and the exosomes from the tumour microenvironment. Our initial findings shows that this micro RNA is up regulated in several cancer cell lines there by reducing NO production in them and the neighbouring Macrophages(by exosome delivery) and thereby giving these cancer cells survival advantage. ACKNOWLEDGEMENT: This research is supported by a grant from the Borroughs Wellcome Fund,NSF-LSAMP,NIH-MARC and a Disability Supplement from NIH-NCI.