Thermal enhancement with optically activated gold nanoshells sensitizes breast cancer stem cells to radiation therapy.
Thermal enhancement with optically activated gold nanoshells sensitizes breast cancer stem cells to radiation therapy.
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DOI：
10.1126/scitranslmed.3001447
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发表时间：
2010-10-27
影响因子：
17.1
通讯作者：
Rosen JM
中科院分区：
文献类型：
--
作者：
Atkinson RL;Zhang M;Diagaradjane P;Peddibhotla S;Contreras A;Hilsenbeck SG;Woodward WA;Krishnan S;Chang JC;Rosen JM
乳腺癌转移和疾病复发被认为是由于残留的癌症干细胞，也被称为肿瘤启动细胞，逃避了最初的治疗。通过使用同基因小鼠和人类三阴性乳腺癌异种移植模型，我们已经证明富含癌症干细胞的亚群比大部分肿瘤细胞对6灰色电离辐射治疗更具抵抗力，因此在电离辐射治疗后48至72小时，它们的相对比例增加。相比之下，我们通过使用静脉注射的光学激活金纳米壳电离辐射后在42°C下局部热疗20分钟，实现了肿瘤大小的更大缩小，而没有同时增加癌症干细胞的百分比。治疗48小时后，与模拟和电离辐射治疗的肿瘤相比，电离辐射加热疗治疗的肿瘤细胞的致瘤性显著降低，表型分化程度更高。因此，我们已经证实，这些癌症干细胞负责体内加速再生，并证明热疗使这些细胞群对放射治疗敏感。这些发现表明，通过金纳米壳加辐射的局部热疗可以消除对辐射有抵抗力的乳腺癌干细胞。
Breast cancer metastasis and disease recurrence are hypothesized to result from residual cancer stem cells, also referred to as tumor-initiating cells, which evade initial treatment. Using both syngeneic mouse and human xenograft models of triple-negative breast cancer, we have demonstrated that a subpopulation enriched in cancer stem cells was more resistant to treatment with 6 gray of ionizing radiation than the bulk of the tumor cells, and accordingly their relative proportion increased 48 to 72 hours after ionizing radiation treatment. In contrast, we achieved a larger reduction in tumor size without a concomitant increase in the percentage of cancer stem cells by treating with local hyperthermia for 20 minutes at 42°C after ionizing radiation using intravenously administered, optically activated gold nanoshells. Forty-eight hours after treatment, cells derived from the tumors treated with ionizing radiation plus hyperthermia exhibited both a marked decrease in tumorigenicity and a more differentiated phenotype than mock- and ionizing radiation–treated tumors. Thus, we have confirmed that these cancer stem cells are responsible for accelerated repopulation in vivo and demonstrated that hyperthermia sensitizes this cell population to radiation treatment. These findings suggest that local hyperthermia delivered by gold nanoshells plus radiation can eliminate radio-resistant breast cancer stem cells.
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影响因子：
16
作者：
Chowdhury, Dipanjan;Xu, Xingzhi;Zhong, Xueyan;Ahmed, Fariyal;Zhong, Jianing;Liao, Ji;Dykxhoorn, Derek M.;Weinstock, David M.;Pfeifer, Gerd P.;Lieberman, Judy
通讯作者：
Lieberman, Judy
影响因子：
11.2
作者：
Charafe-Jauffret E;Ginestier C;Iovino F;Wicinski J;Cervera N;Finetti P;Hur MH;Diebel ME;Monville F;Dutcher J;Brown M;Viens P;Xerri L;Bertucci F;Stassi G;Dontu G;Birnbaum D;Wicha MS
通讯作者：
Wicha MS
影响因子：
3.1
作者：
Calderwood, Stuart K.;Ciocca, Daniel R.
通讯作者：
Ciocca, Daniel R.
影响因子：
3.4
作者：
Horsman, M. R.;Overgaard, J.
通讯作者：
Overgaard, J.
影响因子：
3.5
作者：
FIELD, SB
通讯作者：
FIELD, SB