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Gastrointestinal bleeding: understanding pathogenesis and molecular mechanisms
S164
Educational Exhibit
Posters and Exhibits
Abstract No. 368
Gastrointestinal bleeding: understanding pathogenesis and molecular mechanisms J.B. Jia, R. Oklu; Interventional Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA Learning Objectives: 1. To explore mechanisms of GI bleeding at the microscopic level 2. To understand pathogenesis of intermittent bleeding, vasospasm and barriers to physiologic thrombosis 3. Novel concepts in polymer science and nanotechnology on hemostasis 4. Novel concepts in molecular imaging in the diagnosis of GI bleeding Background: GI bleeding is among the most commonly performed arterial interventions today. Despite significant multidisciplinary efforts, including provocative angiography, GI bleeding interventions can be challenging and difficult to treat with high morbidity and mortality. Clinical Findings/Procedure Details: The aim is to explore mechanisms of bleeding and the subsequent local and systemic physiologic response to bleeding. First, we will review animal models in particular dorsal and cranial windows, perfusion chambers and microfluidic models to understand bleeding at the microscopic level. Histology including electron microscopy of bleeding vasculature will be analyzed. Second, we will explore the response of the injured vessel to bleeding; the response to injury by smooth muscle cells, endothelial layer as well as the blood components will be explored. Finally, we will review novel hemostasis strategies involving nanotechnology and molecular imaging concepts in the diagnosis of GI bleeding. Conclusion and/or Teaching Points: 1. Understand the molecular mechanisms of GI bleeding. 2. Understand the physiologic response to injury by the vessel wall and the components of blood. 3. To learn about both in vivo and in vitro models of bleeding such as anatomic windows, perfusion chambers and microfluidic technologies. 4. Recognize the potential of nanotechnology in delivering diagnostic and therepeutic options in the management of GI bleeding
Abstract No. 369
Posters and Exhibits
Vascular endothelial cells facilitated HCC invasion and metastasis through the Akt and NF-kB pathways induced by paracrine cytokines Y. Wang1, Y. Dong2, L. Xu1, L. Wentao1, J. Cui2; 1 Department of Interventional Therapy, Fudan University Shanghai Cancer Center, Shanghai, China; 2Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China Purpose: Transcatheter arterial chemoembolization is an effective therapy for intermediate-stage HCC. Interrupting
’
JVIR
blood flow to the tumor also create a hypoxic conditions that encourage angiogenesis in HCC. It is well documented that cancer cells secrete angiogenic factors to recruit and sustain tumor vascular networks. However, little is known about the effects of endothelial cells on the behavior of tumor cells. The study was to determine the roles of endothelial cells in HCC cell growth, migration and invasion. Materials and Methods: A mixture of MHCC97H cells and HUVEC cells or MHCC97H cells alone were subcutaneously injected into nude mice to observe the effects of HUVECs on HCC growth. The biological characteristics of MHCC97H cells respectively treated with conditioned medium (CM) derived from HUVECs and endothelial cell basal medium (EBM) in vitro, such as proliferation, migration and invasion, invasion/metastasis associated gene expression, were comparatively analyzed. Differential cytokines between CM and EBM were screened and identified using human cytokine array, related signaling pathways were investigated. Results: Subcutaneous tumorigenicity of MHCC97H cells in mude mice was promoted by HUVECs and its invasion/ metastasis associated genes were significantly upregulated. The, in vitro, proliferation, migration and invasion of HCC cells treated with CM were all significantly enhanced compared as those with EBM stimulation. Simultaneously, PI3K/Akt and ERK1/2 pathway in HCC cells were activated by CM. Total of 25 differential cytokines were identified between CM and EBM. The selected differential cytokines CCL2, IL-8 and CXCL16 all modulated the expressions of HCC invasion/ metastasis genes, especially MMP2 and MMP9. In exposure to CCL2 or CXCL16 alone, upregulation in Akt phosphorylation but no change in ERK phosphorylation were found in MHCC97H cells, moreover the contents of nuclear transcription factor NF-kB were increased compared as the control. Conclusion: This study expands the contribution of endothelial cells to the progression of HCC. It unveils a new paradigm in which endothelial cells function as initiators of molecular crosstalks that enhance survival, migration and invasion of HCC cells.
Educational Exhibit
Abstract No. 370
A review of the pathophysiology of vascular trauma at the cellular level J.B. Jia, R. Oklu; Interventional Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA Learning Objectives: 1. To understand the pathophysiology of vascular injury at the molecular level and to review the body’s response to the injury. 2. To review ischemia, ischemic-reperfusion injury, no reflow phenomenon and vasospasm and their roles in vascular injury. Background: Vascular injury is of great clinical significance and it is imperative for interventionalists to have a thorough understanding since they are involved in treatment and the nature of their work carries the risk of iatrogenic errors resulting in this type of injury. Clinical Findings/Procedure Details: Traumatic vascular injury can be penetrating or blunt with the former causing
Educational Exhibit
Posters and Exhibits
Abstract No. 368
Gastrointestinal bleeding: understanding pathogenesis and molecular mechanisms J.B. Jia, R. Oklu; Interventional Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA Learning Objectives: 1. To explore mechanisms of GI bleeding at the microscopic level 2. To understand pathogenesis of intermittent bleeding, vasospasm and barriers to physiologic thrombosis 3. Novel concepts in polymer science and nanotechnology on hemostasis 4. Novel concepts in molecular imaging in the diagnosis of GI bleeding Background: GI bleeding is among the most commonly performed arterial interventions today. Despite significant multidisciplinary efforts, including provocative angiography, GI bleeding interventions can be challenging and difficult to treat with high morbidity and mortality. Clinical Findings/Procedure Details: The aim is to explore mechanisms of bleeding and the subsequent local and systemic physiologic response to bleeding. First, we will review animal models in particular dorsal and cranial windows, perfusion chambers and microfluidic models to understand bleeding at the microscopic level. Histology including electron microscopy of bleeding vasculature will be analyzed. Second, we will explore the response of the injured vessel to bleeding; the response to injury by smooth muscle cells, endothelial layer as well as the blood components will be explored. Finally, we will review novel hemostasis strategies involving nanotechnology and molecular imaging concepts in the diagnosis of GI bleeding. Conclusion and/or Teaching Points: 1. Understand the molecular mechanisms of GI bleeding. 2. Understand the physiologic response to injury by the vessel wall and the components of blood. 3. To learn about both in vivo and in vitro models of bleeding such as anatomic windows, perfusion chambers and microfluidic technologies. 4. Recognize the potential of nanotechnology in delivering diagnostic and therepeutic options in the management of GI bleeding
Abstract No. 369
Posters and Exhibits
Vascular endothelial cells facilitated HCC invasion and metastasis through the Akt and NF-kB pathways induced by paracrine cytokines Y. Wang1, Y. Dong2, L. Xu1, L. Wentao1, J. Cui2; 1 Department of Interventional Therapy, Fudan University Shanghai Cancer Center, Shanghai, China; 2Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China Purpose: Transcatheter arterial chemoembolization is an effective therapy for intermediate-stage HCC. Interrupting
’
JVIR
blood flow to the tumor also create a hypoxic conditions that encourage angiogenesis in HCC. It is well documented that cancer cells secrete angiogenic factors to recruit and sustain tumor vascular networks. However, little is known about the effects of endothelial cells on the behavior of tumor cells. The study was to determine the roles of endothelial cells in HCC cell growth, migration and invasion. Materials and Methods: A mixture of MHCC97H cells and HUVEC cells or MHCC97H cells alone were subcutaneously injected into nude mice to observe the effects of HUVECs on HCC growth. The biological characteristics of MHCC97H cells respectively treated with conditioned medium (CM) derived from HUVECs and endothelial cell basal medium (EBM) in vitro, such as proliferation, migration and invasion, invasion/metastasis associated gene expression, were comparatively analyzed. Differential cytokines between CM and EBM were screened and identified using human cytokine array, related signaling pathways were investigated. Results: Subcutaneous tumorigenicity of MHCC97H cells in mude mice was promoted by HUVECs and its invasion/ metastasis associated genes were significantly upregulated. The, in vitro, proliferation, migration and invasion of HCC cells treated with CM were all significantly enhanced compared as those with EBM stimulation. Simultaneously, PI3K/Akt and ERK1/2 pathway in HCC cells were activated by CM. Total of 25 differential cytokines were identified between CM and EBM. The selected differential cytokines CCL2, IL-8 and CXCL16 all modulated the expressions of HCC invasion/ metastasis genes, especially MMP2 and MMP9. In exposure to CCL2 or CXCL16 alone, upregulation in Akt phosphorylation but no change in ERK phosphorylation were found in MHCC97H cells, moreover the contents of nuclear transcription factor NF-kB were increased compared as the control. Conclusion: This study expands the contribution of endothelial cells to the progression of HCC. It unveils a new paradigm in which endothelial cells function as initiators of molecular crosstalks that enhance survival, migration and invasion of HCC cells.
Educational Exhibit
Abstract No. 370
A review of the pathophysiology of vascular trauma at the cellular level J.B. Jia, R. Oklu; Interventional Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA Learning Objectives: 1. To understand the pathophysiology of vascular injury at the molecular level and to review the body’s response to the injury. 2. To review ischemia, ischemic-reperfusion injury, no reflow phenomenon and vasospasm and their roles in vascular injury. Background: Vascular injury is of great clinical significance and it is imperative for interventionalists to have a thorough understanding since they are involved in treatment and the nature of their work carries the risk of iatrogenic errors resulting in this type of injury. Clinical Findings/Procedure Details: Traumatic vascular injury can be penetrating or blunt with the former causing