Day 2 :
Keynote Forum
Jaime Tisnado
Virginia Commonwealth University, USA
Keynote: Carotid blow out syndrome: Interventional radiologic management
Time : 09:30-10:15
Biography:
Jaime Tisnado graduated from Leoncio Prado Military Academy. He received his BM degree from San Marcos National University, College of Sciences. He received his MD degree summa cum laude from the same San Marcos National University Medical School. He was an Intern at GBMC, a division of John's Hopkins University Hospital in Baltimore, MD, 1965, and then an Intern and Resident in Surgery at The State University of New York, Upstate Medical Center in Syracuse NY, 1966-67. He was a Resident in Radiology for 4 years at Thomas Jefferson University Medical Center in Philadelphia, 1967-71. Then he took 2 years fellowships in Vascular and Interventional Radiology and Neuroradiology both at the same institution, Thomas Jefferson University in Philadelphia, PA, 1971-73. He then became an Assistant Professor of Radiology and Director of Interventional Radiology at Albany Medical College, Albany, NY, 1974-77. Thereafter he moved to Virginia Commonwealth University, in Richmond, VA, where he became Associate Professor of Radiology and Director of Interventional Radiology and eventually became Professor of Radiology and Professor of Surgery, at the same university from 1985 till 2010. Thereafter, he was named one of the few Professor Emeritus of Radiology and Surgery, all at the same Virginia Commonwealth University in 2010 till now. He has published more than 100 articles in peer reviewed journals, about 400 scientific posters and electronic exhibits all over the country and the world, and about 200 abstracts, 4 books, many chapters in books, and about 200 papers presented at meetings, at the local, national, and worldwide level. He has been selected many times to Who is Who in America, the Best Radiologists in America, the Best Physicians in USA, etc. Moreover, he is the only person in the country and in the world who has, at the same time and forever, more than 5 fellowships in the most prestigious professional organizations of USA.
Abstract:
Carotid blow out syndrome (CBOS) is a catastrophic neurovascular emergency associated with a high morbidity and mortality (M&M). The etiology of CBOS is: head and neck malignancies with tumor invasion, postoperative complications, inflammation, trauma, vasculitides, collagen diseases, and post radiation therapy for malignancies, among others. The conventional surgical management has been and is carotid artery and/or branch ligation or bypass, and is rather difficult and associated with significant M&M and could be ineffective in controlling the situation. At this time, the ideal management of this serious problem is the interventional radiology (IR) and interventional neuroradiology (INR) endovascular: insertion of stents of different kinds (covered or uncovered, self-expanding or balloon-expandable) and/or embolization of the carotid or vertebral arteries or branches, with temporary or permanent agents and/or devices. A permanent or temporary success is expected with stent insertion and/or embolization, or both procedures combined. We have managed many patients, not considered ideal candidates for surgery, at least during the acute phase, with stents from different manufacturers, mostly covered. In addition, we have embolized some patients as well and some other patients have had both methods. The procedures have been done in the IR suite by the IR, INR and surgeons as well, working in a team, in a collaborative rather than in an adversarial manner. No major complications related to the procedures have been found. The patients have had a long-term or a temporary improvement in their condition. The emergent management of CBOS by stenting and/or embolization or both is a safe, effective and relatively easy procedure to temporarily manage these seriously ill patients. A longer follow-p and many more patients studied are necessary to establish the definitive role of stenting and/or embolization in CBOS. In conclusion, the conventional surgical management of CBOS may be difficult and/or ineffective, therefore, the endovascular management is considered the first choice of therapy, at least for now, especially in clinically desperate situations.
Keynote Forum
Kang-Yell Choi
Yonsei University, South Korea
Keynote: Degradation of both β-catenin and RAS via targeting the Wnt/β-catenin pathway is an ideal approach for colorectal cancer treatment
Time : 10:15-11:00
Biography:
Kang-Yell Choi finished his doctorate in Biochemistry at the Purdue University in 1993, and performed research related with cell signaling with the yeast pheromone signaling pathway as a model system at Harvard Medical School as a postdoctoral fellow. There, he characterized Saccharomyces Ste5 functioning at the MAP kinase pathway as a 1st protein introduced concept for the "Scaffold Protein" in the community. In 1995, he returned back to Korea as a professor of Yonsei University. Since then, he has been working on mammalian cell signaling related with several different pathophysiologies such as growth control of cells and human cancer. He is serving as the chief of the National Research Laboratory of the Molecular Complex Control for recent 5 years, and currently positioned as the Director of the Translational Research Center for Protein Function Control supported by Ministry of Science, ICT and Future Panning of Korea.
Abstract:
Interaction between the Wnt/beta-catenin and the Ras-ERK pathways, two major transforming pathways, have been posited. However, molecular mechanisms and cooperative roles of these two pathways are poorly understood. Both APC and KRAS mutations synergistically promote cellular transformation and tumor growth, attributed to activation of the RAS-ERK pathway via activation of the Wnt/ β-catenin signaling. One key event in this crosstalk is the stabilization of RAS, especially mutant KRAS, by APC loss. Stabilization of both β-catenin and RAS plays a critical role in the synergistic transformation, and both β-catenin and RAS levels are highly increased in CRC patient tissues. Epidermal growth factor receptor (EGFR), a direct transcriptional target of the Wnt/β-catenin signaling pathway, is also overexpressed in human CRC, and plays a role in the synergistic tumorigenesis. Therefore, inhibition of both the Wnt/β-catenin and EGFR-RAS-ERK pathways, especially by reducing levels of the proteins elevated in CRC, could be an ideal approach for the treatment of human CRC. This concept for an ideal therapeutic approach has been proved by small molecules destabilizing both β-catenin and RAS by activation of GSK3β via targeting the Wnt/β-catenin pathway. GSK3β activated by the small molecules induce phosphorylation and subsequent polyubiquitin-dependent proteasomal degradations of both β-catenin and Ras and subsequent transcriptional suppression of EGFR overcome current limitation of the insensitiveness of the EGFR targeting therapies such as cetuximab attributed by a K-Ras mutation of patients. Moreover, these small molecules effectively suppress activaiton of cancer stem cell activated through aberrancies of the Wnt/ β-catenin and Ras-ERK pathways.
Keynote Forum
Christopher S Lange
SUNY Downstate Medical Center, Brooklyn, NY, USA
Keynote: Applying Koch’s postulates to test the cancer stem cell basis of cancer
Time : 11:20-12:00
Biography:
Christopher S Lange Associate Chair, Department of Radiation Oncology, SUNY Downstate Medical Center, Brooklyn (2010-Present), Professor of Molecular and Cell Biology, School of Graduate Studies, SUNY Downstate Medical Center (1992-Present), Professor, Director, Radiobiological Division, Department of Radiation Oncology, SUNY Downstate Medical Center (1980-Present), Associate Director, Residency Program, SUNY Downstate Medical Center (2009), Assistant Professor of Radiology, Radiation Biology and Biophysics,, University of Rochester School of Medicine and Dentistry, New York (1969-1980), NHS Senior Research Officer, Christie Hospital and Holt Radium Institute, Manchester, England (1968-1969), NHS Research Officer, Christie Hospital and Holt Radium Institute, Manchester, England (1962-1968), MRC Research Assistant, Radiobiology Laboratory, Churchill Hospital, Headington, England (1961-1962).
Abstract:
We tested the cancer stem cell (CSC) hypothesis using the patented Hybrid Spheroid (HS) Assay (HSA) and by applying Koch’s postulates to test its validity. The HSA is an in vitro assay that enables one to take a viable sample of an individual patient’s tumor, make a single cell suspension, mix it in known proportions with human fibroblasts (AG1522) and dispense a known number of cells of the mixture into each well of ultra low attachment (ULA) 96-well plates to agglomerate into 1 HS/well, each containing an average of <1 CSC. The HS provides an analog of the CSC niche, enabling the CSC to proliferate (with some daughters differentiating into amplifying transit cells (ATCs)) and undergo 10–15 symmetric divisions before exhausting the nutrients. This satisfies the McCulloch and Till (spleen colony assay) requirements for a stem cell. Applying Koch’s postulates, we answer the following questions: Does the patient’s tumor contain cells with CSC properties?; Can we isolate and propagate these cells?; Can these cells induce the tumor in vivo?; Do these cells contain and express specific gene products that give them CSC properties?; If we disrupt these genes, do the cells lose their CSC properties?; If we eliminate the CSCs do we eliminate the cancer? The HSA was applied to tumor samples taken from individual endometrial adenocarcinoma patients and correctly predicted, based on CSC radioresistance, in patients who fail their standard-of-care treatments. It was therefore concluded that the CSC hypothesis is validated in the HSA.