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首页 » Clin Cancer Res: 新的、非侵袭性方法——鉴定淋巴结转移

Clin Cancer Res: 新的、非侵袭性方法——鉴定淋巴结转移

来源:生物谷 2012-01-15 07:36

利用乳腺癌淋巴结转移中高度表达的两个细胞表面标志物,Moffitt癌症中心的研究人员与其他研究院的同事一起工作,开发出定向荧光分子成像探针,它能非侵袭性地检测乳腺癌的淋巴结转移。新程序可以降低乳腺癌病人侵袭性与不可靠的哨兵淋巴结(SLN)活组织检查和手术相关的阴性副作用。

他们的研究发表在Clinical Cancer Research上,这是美国癌症研究协会的公开出版物。

高达74%的乳腺癌患者都经历过哨兵淋巴结活检,结果发现腋窝淋巴结或前淋巴结转移是阴性的,通讯作者David L. Morse博士说,他是Moffitt研究所的副会员,其研究领域包括实验治疗与诊断成像,"测定前淋巴结转移的存在与否对于乳腺癌分期与预后很关键。因为哨兵淋巴结活检的不可靠性和潜在的副作用,迫切需要一种非侵袭性的、更精确的方法来评估淋巴结参与乳腺癌的转移。"

作者指出,哨兵淋巴结活检的术后并发症包括淋巴水肿、血清肿形成、感觉神经损伤和病人活动范围受限。此外,腋窝淋巴结活检不能确定5%-10%患者的疾病。

在开发识别乳腺癌腋窝淋巴结转移的靶向分子探针中,来自Moffitt研究所、亚利桑那大学和佛罗里达大学的研究小组利用了2个细胞表面标志物--CAIX 和CAXII。CAIX是一种细胞表面标志物, "在乳腺癌淋巴结转移中高度、广泛表达",在正常组织中不表达。

Morse 解释说,CAIX 和CAXII两者都是完全的质膜蛋白伴有较大的细胞外组分,这些细胞外组分很容易与靶向成像探针接触并结合。另外,一些研究表明,CAIX表达是与负性预后、抗化疗和放射治疗乳腺癌相关。CAXII是一种在超过75%的腋窝淋巴结转移患者中表达的蛋白。

研究人员接着通过使用特异性地与CAIX 和CAXII结合的单克隆抗体开发了他们的靶向试剂,CAIX 和CAXII都已知能促进肿瘤的生长。

研究人员称,已经对许多评估前哨淋巴结的无创光学成像程序进行了调查研究,但是这些评估方法缺乏靶向肿瘤转移标志物的能力。

"这些方法只提供了解剖学图形,没有检测存在于淋巴结的肿瘤细胞",Morse这样解释,"使用小鼠乳腺癌转移模型和一种新的、基于单克隆抗体的分子成像剂,我们开发出了利用荧光成像检测ALN转移的一种定向的、非侵袭性方法"。

除了用小鼠的成像研究外,研究人员也报道了,联合CAIX 和CAXII对组织微阵列(TMA)研究中患者损赠的样本进行检测,结果达到了100%的符合率。

"在ALNs中检测肿瘤细胞的成像探针具有高灵敏度", Morse解释说,"无论是CAIX 还是CAXII,均表达于该项研究中所调查的100%的乳腺癌淋巴结转移样本中。这些成像探针有望在临床中对乳腺癌进行分期提供一种非侵入性检测方式,它没有进行一些不必要的昂贵的手术。"(生物谷bioon.com)

Noninvasive Detection of Breast Cancer Lymph Node Metastasis Using Carbonic Anhydrases IX and XII Targeted Imaging Probes

Narges K. Tafreshi, Marilyn M. Bui, Kellsey Bishop, Mark C. Lloyd, Steven A. Enkemann, Alexis S. Lopez, Dominique Abrahams, Bradford W. Carter, Josef Vagner, Stephen R. Gobmyer, Robert J. Gillies, and David L. Morse

Abstract Purpose: To develop targeted molecular imaging probes for the noninvasive detection of breast cancer lymph node metastasis. Experimental Design: Six cell surface or secreted markers were identified by expression profiling and from the literature as being highly expressed in breast cancer lymph node metastases. Two of these markers were cell surface carbonic anhydrase isozymes (CAIX and/or CAXII) and were validated for protein expression by immunohistochemistry of patient tissue samples on a breast cancer tissue microarray containing 47 normal breast tissue samples, 42 ductal carcinoma in situ, 43 invasive ductal carcinomas without metastasis, 46 invasive ductal carcinomas with metastasis, and 49 lymph node macrometastases of breast carcinoma. Targeted probes were developed by conjugation of CAIX- and CAXII-specific monoclonal antibodies to a near-infrared fluorescent dye. Results: Together, these two markers were expressed in 100% of the lymph node metastases surveyed. Selectivity of the imaging probes were confirmed by intravenous injection into nude mice-bearing mammary fat pad tumors of marker-expressing cells and nonexpressing cells or by preinjection of unlabeled antibody. Imaging of lymph node metastases showed that peritumorally injected probes detected nodes harboring metastatic tumor cells. As few as 1,000 cells were detected, as determined by implanting, under ultrasound guidance, a range in number of CAIX- and CAXII-expressing cells into the axillary lymph nodes. Conclusion: These imaging probes have potential for noninvasive staging of breast cancer in the clinic and elimination of unneeded surgery, which is costly and associated with morbidities. Clin Cancer Res; 18(1); 207-19. ?2011 AACR.

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