Intraoperative assessment of non-melanoma skin cancer margins using NIRF probes.

使用 NIRF 探针对非黑色素瘤皮肤癌边缘进行术中评估。

• 批准号: 8711905
• 负责人: Brian Straight
• 金额: $ 14.98万
• 依托单位: AKROTOME IMAGING, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-06 至 2015-03-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8711905
• 关键词: Achievement; Address; Adoption; Area; Basal cell carcinoma; Binding; Biopsy; Cancerous; Cathepsins; Cathepsins B; Characteristics; Clinical; Computer software; Conventional Surgery; Cosmetics; Dermatologic; Dermatologist; Disadvantaged; Disease; Drug Formulations; Effectiveness; Enzymes; Excision; Face; Fluorescence; Fluorescent Probes; Foundations; Goals; Gold; Hand; Hot Spot; Image; Image Analysis; Imaging Device; Imaging technology; Incidence; Incubated; Infiltration; Ink; Invaded; Legal patent; Lesion; Light; Malignant Neoplasms; Marketing; Measures; Medical center; Mohs Surgery; Normal tissue morphology; Operative Surgical Procedures; Outcome; Pathology; Patient Care; Patients; Peptide Hydrolases; Phase; Photons; Postoperative Period; Predictive Value; Procedures; Process; Public Health; Recurrence; Repeat Surgery; Resected; Sampling; Sensitivity and Specificity; Signal Transduction; Site; Skin; Skin Cancer; Skin Carcinoma; Skin Neoplasms; Specimen; Speed; Squamous cell carcinoma; Sunlight; System; Techniques; Technology; Testing; Therapeutic; Time; Tissue Sample; Tissues; Topical application; Training; Training Support; Tumor Debulking; Tumor Tissue; University Hospitals; Work; base; cancer cell; cancer surgery; clinical decision-making; cost; cost effective; design; imaging probe; improved; instrument; laboratory facility; molecular imaging; novel; overexpression; prototype; public health relevance; tool; tumor

DESCRIPTION (provided by applicant): The incidence of skin cancer is increasing rapidly in the US. In 1994, there were around 1 million cases of non-melanoma skin cancer per year; this number had grown to more than 4 million by 2011. Many of these tumors appear in areas of the body that are exposed to sunlight (face, hands, etc.), where cosmetic considerations require minimizing resection of normal tissue. More generally, however, successful skin surgery requires the complete removal of diseased tissue while minimizing removal of healthy tissues. While standard surgical approaches may remove more healthy tissue than necessary or fail to remove all cancerous tissue, Mohs Micrographic Surgery (MMS) can achieve the above requirements, offering improved outcomes, lower chances of disease recurrence, better cosmetic results and minimal removal of healthy tissue compared to standard surgical approaches. However, MMS is time-consuming, has low patent throughput, requires specialized clinical training and on-site laboratory facilities. Moreover, it has been recommended that MMS only be used on a small subset of skin cancers conforming to specific characteristics [35]. The lack of a cost-effective, easy-to-use alternative to MMS and standard surgical approaches represents a significant, unmet clinical need that has yet to be addressed. In this Phase I submission, we propose to develop a simple, inexpensive and rapid imaging technology to identify cancer in resected tissues during surgery. Such a technology would bring the advantages of MMS surgery to many non-melanoma skin cancer resections while mitigating or eliminating the disadvantages of MMS. Our proposed approach is to topically apply a proprietary, smart, protease binding near- infrared fluorescent (NIRF) probe ex vivo to excised skin tumor tissue. Because many forms of cancer rely on specific proteases (known as cathepsins B or L) in order to invade surrounding normal tissue, the probe is designed to fluoresce under near-infrared light when it encounters active enzyme. Because it activates quickly, results can inform clinical decision-making almost immediately. The proposed technology can have a significant public health impact. Adaptation of this procedure into patient care can happen very rapidly and has the potential to radically improve the treatment of non-melanoma skin cancers, reducing costs, improving outcomes, and reducing complications for many patients. Phase I work involves: Studies to measure the activation of topically-administered probe by active proteases in skin biopsies. We will work with a Mohs-trained dermatologist to obtain discarded tumor tissue samples. We will apply probe to them and image them. Correlation of probe activation with cancer cells and active cathepsins. Statistical analysis to determine the accuracy (sensitivity and specificity) of the test to determine if it is useful as an intraoperative clinical tool to assess skin cancer resections.

描述（由申请人提供）：皮肤癌的发病率在美国迅速增加。1994年，每年约有100万例非黑色素瘤皮肤癌病例;到2011年，这一数字已增长到400多万例。这些肿瘤中的许多出现在暴露于阳光的身体区域（面部，手部等），其中美观的考虑需要最小化正常组织的切除。然而，更一般地，成功的皮肤手术需要完全去除患病组织，同时最小化健康组织的去除。虽然标准手术方法可能会切除比必要更多的健康组织或无法切除所有癌组织，但莫氏显微手术（MMS）可以达到上述要求，与标准手术方法相比，提供更好的结果，更低的疾病复发机会，更好的美容效果和最小的健康组织切除。然而，MMS是耗时的，具有低专利吞吐量，需要专门的临床培训和现场实验室设施。此外，建议MMS仅用于符合特定特征的一小部分皮肤癌[35]。MMS和标准手术入路缺乏具有成本效益且易于使用的替代方案，这是一个尚未解决的重大未满足的临床需求。在第一阶段提交的材料中，我们建议开发一种简单、廉价和快速的成像技术，以在手术过程中识别切除组织中的癌症。这种技术将为许多非黑色素瘤皮肤癌切除术带来MMS手术的优点，同时减轻或消除MMS的缺点。我们提出的方法是局部应用专有的，智能的，蛋白酶结合近红外荧光（NIRF）探针离体切除皮肤肿瘤组织。由于许多形式的癌症依赖于特定的蛋白酶（称为组织蛋白酶B或L）来侵入周围的正常组织，因此探针被设计为当遇到活性酶时在近红外光下发出荧光。因为它激活迅速，结果几乎可以立即告知临床决策。拟议的技术可能会对公共卫生产生重大影响。将该程序应用于患者护理可以非常迅速地进行，并有可能从根本上改善非黑色素瘤皮肤癌的治疗，降低成本，改善结果，并减少许多患者的并发症。第一阶段的工作包括：研究测量皮肤活检中活性蛋白酶对局部给药探针的激活作用。 我们将与接受过莫氏培训的皮肤科医生合作，以获得废弃的肿瘤组织样本。我们将对它们进行探测并成像。 探针活化与癌细胞及活性组织蛋白酶的相关性。 统计分析，以确定测试的准确性（灵敏度和特异性），以确定其是否是 可用作评估皮肤癌切除术的术中临床工具。

项目成果

Tyrosine kinase signaling-independent MET-targeting with CAR-T cells.

• DOI: 10.1186/s12967-023-04521-9
• 发表时间: 2023-10-01
• 期刊: JOURNAL OF TRANSLATIONAL MEDICINE
• 影响因子: 7.4
• 作者: Qin, Anna;Qin, Yuan;Lee, Joseph;Musket, Anna;Ying, Mingyao;Krenciute, Giedre;Marincola, Francesco M.;Yao, Zhi Q.;Musich, Phillip R.;Xie, Qian
• 通讯作者: Xie, Qian

Chimeric antigen receptor T-cell therapy in glioblastoma: charging the T cells to fight.

• DOI: 10.1186/s12967-020-02598-0
• 发表时间: 2020-11-11
• 期刊: Journal of translational medicine
• 影响因子: 7.4
• 作者: Land CA;Musich PR;Haydar D;Krenciute G;Xie Q
• 通讯作者: Xie Q