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功能放射性核素成像、体外放射性碘摄取估计及逆转录聚合酶链反应在评估乳腺癌中碘化钠转运体(NIS)表达和功能的初步研究

Functional Radionuclide Imaging, In-Vitro Radioiodine Uptake Estimation and RT-PCR in the Evaluation of Sodium Iodide Symporter (NIS) Expression and Functionality in Breast Cancer: A Pilot Study.

作者信息

Joseph J K, Patel R B, Damle A A, Nair N, Badwe R A, Basu S

机构信息

Radiation Medicine Centre, Bhabha Atomic Research Centre, TATA Memorial Hospital Annexe, Jerbai Wadia Road, Parel, Mumbai, 400 012 India ; Department of Radiotherapy and Oncology, Govt. Medical College, Kottayam, Kerala 686 008 India.

Radiation Medicine Centre, Bhabha Atomic Research Centre, TATA Memorial Hospital Annexe, Jerbai Wadia Road, Parel, Mumbai, 400 012 India.

出版信息

Indian J Surg Oncol. 2013 Mar;4(1):80-91. doi: 10.1007/s13193-012-0205-8. Epub 2013 Jan 5.

Abstract

Breast cancer is a common malignancy in females, which is considered as a systemic disease, whose treatment involves combined modality including systemic as well as local treatment. Recent studies have shown that breast cancer also expresses Sodium Iodide Symporter (NIS) gene, like in the thyroid, which is the factor responsible for the uptake of iodide by the thyroid, enabling radioiodine therapy of thyroid disorders. This study aimed to evaluate various radionuclide imaging characteristics, in vitro radioiodine uptake (RAIU) and evaluation of NIS expression by using Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) to explore sodium iodide symporter (NIS) expression and iodine uptake in breast cancer and to explor e whether radioiodine can be used for the diagnosis and treatment of breast cancer. Ways of differential regulation of NIS expression in breast cancer has also been explored. Female patients with palpable breast lump and histologically proven infiltrating duct carcinoma were taken up for the study, which included 50 females of mean age 49 years. (range: 23-73 years). The patients were categorized into different groups, depending on the type of the study performed. The uptake patterns in various imaging modalities were analyzed and compared with invitro and RT-PCR studies. 68 % of breast cancer cases showed (99m)Tc-pertechnetate uptake at the initial images. This finding could partly be due to tumor vascularity, which is usually higher compared to the normal tissues. The uptake in the delayed imaging could be related to that due to NIS in the breast. Use of perchlorate or stable iodine did not alter the pertechnetate uptake pattern in breast tumor. Good correlation between (99m)Tc-pertechnetate and (99m)Tc-tetrofosmin uptake in breast cancer was demonstrated. In vitro radioactive iodine uptake in the breast tumor was significantly higher than that in the normal breast tissue. Only 42 % of breast tumor samples studied using RT-PCR showed NIS expression. Correlation between (99m)Tc-pertechnetate uptake and NIS expression could not be well established. Further studies with higher dose of radioiodine and/or mechanisms of differentially blocking the thyroid are required to assess the feasibility of radioiodine therapy for breast cancer.

摘要

乳腺癌是女性常见的恶性肿瘤,被视为一种全身性疾病,其治疗涉及全身治疗和局部治疗相结合的方式。最近的研究表明,乳腺癌也表达钠碘同向转运体(NIS)基因,就像甲状腺一样,该基因是甲状腺摄取碘的负责因子,使得放射性碘能够用于治疗甲状腺疾病。本研究旨在评估各种放射性核素成像特征、体外放射性碘摄取(RAIU),并通过逆转录聚合酶链反应(RT-PCR)评估NIS表达,以探索乳腺癌中钠碘同向转运体(NIS)的表达和碘摄取情况,并探究放射性碘是否可用于乳腺癌的诊断和治疗。还探索了乳腺癌中NIS表达的差异调节方式。纳入研究的为有可触及乳腺肿块且经组织学证实为浸润性导管癌的女性患者,共50名,平均年龄49岁(范围:23 - 73岁)。根据所进行的研究类型,将患者分为不同组。分析了各种成像模式下的摄取模式,并与体外研究和RT-PCR研究进行比较。68%的乳腺癌病例在初始图像上显示有高锝酸盐(99m)Tc摄取。这一发现部分可能归因于肿瘤血管,肿瘤血管通常比正常组织更丰富。延迟成像中的摄取可能与乳腺中NIS有关。使用高氯酸盐或稳定碘不会改变乳腺肿瘤中的高锝酸盐摄取模式。证明了乳腺癌中高锝酸盐(99m)Tc与替曲膦(99m)Tc摄取之间具有良好的相关性。乳腺肿瘤的体外放射性碘摄取明显高于正常乳腺组织。使用RT-PCR研究的乳腺肿瘤样本中只有42%显示有NIS表达。高锝酸盐(99m)Tc摄取与NIS表达之间的相关性未能很好地确立。需要进一步进行更高剂量放射性碘的研究和/或不同程度阻断甲状腺的机制研究,以评估放射性碘治疗乳腺癌的可行性。

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Tissue iodine content and serum-mediated 125I uptake-blocking activity in breast cancer.
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