EndoPulse System for Endoscopic Ultrasound-Guided Therapy of Pancreatic Carcinoma

用于内镜超声引导治疗胰腺癌的 EndoPulse 系统

• 批准号: 8002232
• 负责人: RICHARD Lee NUCCITELLI
• 金额: $ 47.3万
• 依托单位: BIOELECTROMED CORPORATION
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8002232
• 关键词: Ablation; Accounting; Adverse effects; Amylases; Apoptosis; Area; Biochemical; Blood Pressure; Breathing; Cancer Death Rates; Carcinoma; Cell Membrane Permeability; Cells; Clinical; Clinical Trials; Data; Diagnosis; Disease; Disease remission; Electrocardiogram; Electrodes; Endoscopes; Evaluation; Family suidae; Fever; Frequencies; Gastroscopes; Goals; Hemorrhage; Histologic; Housing; Human; Image; In Situ Nick-End Labeling; Incidence; Induction of Apoptosis; Infection; Intracellular Membranes; Label; Lead; Lipase; Location; Malignant neoplasm of pancreas; Medical Device; Medical center; Modeling; Monitor; Morbidity - disease rate; Mus; Needles; Neoadjuvant Therapy; Operative Surgical Procedures; Pancreas; Pancreatic carcinoma; Pancreatitis; Patients; Permeability; Phase; Physiologic pulse; Procedures; Safety; Serum; Site; Skin Cancer; Skin Neoplasms; Solid Neoplasm; Squamous cell carcinoma; Staining method; Stains; Stomach; System; Technology; Testing; Tissues; Tube; Ultrasonography; Xenograft Model; caspase-3; effective therapy; electric field; flexibility; in vivo; melanoma; minimally invasive; mortality; nanosecond; neoplastic cell; pancreatic neoplasm; prototype; public health relevance; subcutaneous; tumor; tumor eradication

DESCRIPTION (provided by applicant): BioElectroMed is developing a new medical device called the EndoPulse that will deliver nanosecond pulsed electric fields (nsPEF) to treat pancreatic carcinomas. We have extensive evidence supporting the efficacy of nsPEF in eliminating all three types of skin cancer, basal and squamous cell carcinoma and melanoma. The mechanism by which nsPEF causes tumor regression involves increasing the permeability of intracellular membranes and triggering apoptosis. This electric field-induced membrane permeability increase is not cell specific so the same pulse parameters that are effective at eliminating skin tumors should also be effective at treating pancreatic tumors. The main advantage of this nsPEF application over other tumor treatments is that it minimizes damage to healthy tissue surrounding the tumor. Only cells located within the electrode array are stimulated by nsPEF application to undergo apoptosis. The main challenge is the accurate placement of the electrodes around the tumor and this will be accomplished using endoscopic ultrasound (EUS). The EndoPulse electrodes will be inserted down the accessory channel of the endoscope and guided to the tumor using ultrasound imaging. During Phase I of this project we have three specific aims: 1) Fabricate a nanosecond pulsed electric field (nsPEF) electrode compatible with endoscopic ultrasound and capable of applying nsPEF to pancreatic tumors; 2) Determine the optimal pulse parameters to use with the EndoPulse electrode to trigger apoptosis in pancreatic tumors using a murine subcutaneous xenograft model; 3) Demonstrate safety and feasibility of EUS-guided nsPEF ablation of normal pancreatic tissue in a pig. Phase II will then launch clinical trials at Stanford Medical Center under the direction of Dr. Ann Chen. If the EndoPulse can reliably eliminate pancreatic carcinomas, it would offer a much needed breakthrough in the treatment of this deadly disease. PUBLIC HEALTH RELEVANCE: We are developing a new medical device, the EndoPulse, for treating pancreatic carcinoma for which there are currently no effective therapies. The EndoPulse exposes the tumor to ultrashort electrical pulses which permeabilize intracellular membranes and trigger apoptosis or programmed cell death. This causes pancreatic carcinomas to self-destruct. The EndoPulse is guided to the carcinoma via an accessory channel in an ultrasound imaging endoscope which will also be used to image the placement of the electrodes around the tumor. Endoscopically delivered electrical pulses to trigger tumor remission offers a much needed breakthrough in the treatment of pancreatic cancer.

描述（由申请人提供）：BioElectroMed 正在开发一种名为 EndoPulse 的新型医疗设备，该设备将提供纳秒脉冲电场 (nsPEF) 来治疗胰腺癌。我们有大量证据支持 nsPEF 在消除所有三种类型的皮肤癌、基底细胞癌和鳞状细胞癌以及黑色素瘤方面的功效。 nsPEF 引起肿瘤消退的机制涉及增加细胞内膜的通透性并引发细胞凋亡。这种电场引起的膜通透性增加不是细胞特异性的，因此能够有效消除皮肤肿瘤的相同脉冲参数也应该能够有效治疗胰腺肿瘤。与其他肿瘤治疗相比，这种 nsPEF 应用的主要优点是最大限度地减少对肿瘤周围健康组织的损害。只有位于电极阵列内的细胞才会受到 nsPEF 应用的刺激而发生凋亡。主要挑战是在肿瘤周围准确放置电极，这将通过超声内镜 (EUS) 来完成。 EndoPulse 电极将插入内窥镜的辅助通道，并使用超声成像引导至肿瘤。在该项目的第一阶段，我们有三个具体目标：1）制造与内窥镜超声兼容的纳秒脉冲电场（nsPEF）电极，并能够将nsPEF应用于胰腺肿瘤； 2) 使用小鼠皮下异种移植模型确定与 EndoPulse 电极一起使用以触发胰腺肿瘤细胞凋亡的最佳脉冲参数； 3) 证明 EUS 引导下 nsPEF 消融猪正常胰腺组织的安全性和可行性。随后，第二阶段将在 Ann Chen 博士的指导下在斯坦福医学中心启动临床试验。如果 EndoPulse 能够可靠地消除胰腺癌，它将为这种致命疾病的治疗提供急需的突破。 公共健康相关性：我们正在开发一种新的医疗设备 EndoPulse，用于治疗目前尚无有效疗法的胰腺癌。 EndoPulse 将肿瘤暴露于超短电脉冲下，使细胞内膜通透并引发细胞凋亡或程序性细胞死亡。这会导致胰腺癌自毁。 EndoPulse 通过超声成像内窥镜中的辅助通道引导至肿瘤，该内窥镜也将用于对肿瘤周围电极的放置进行成像。内窥镜递送的电脉冲触发肿瘤缓解为胰腺癌的治疗提供了急需的突破。