Local and Systemic Antitumor Effects of Photo-activatable Paclitaxel Prodrug on Rat Breast Tumor Models.
Local and Systemic Antitumor Effects of Photo-activatable Paclitaxel Prodrug on Rat Breast Tumor Models.
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DOI：
10.1111/php.13202
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发表时间：
2020-05
影响因子：
3.3
通讯作者：
You Y
中科院分区：
文献类型：
--
作者：
Subramaniyan B;Rajaputra P;Nguyen L;Li M;Peer CJ;Kindrick J;Figg WD;Woo S;You Y
我们证明了一个大的原发性和一个小的未经治疗的远处乳腺癌可以通过我们的光激活紫杉醇（PTX）前药局部治疗来控制。我们推测，光动力治疗（PDT）和局部释放的PTX联合作用会损害肿瘤，而全身抗肿瘤作用会抑制远处肿瘤。通过皮下注射MAT B III细胞，建立Fischer 344大鼠同基因乳腺癌模型（单肿瘤模型和双肿瘤模型）。给大鼠注射PTX前药（剂量：1 μ mol kg−1，静脉注射），用690 nm激光（75或140 mW cm−1，圆柱形光扩散器，药光间隔[DLI] 9 h）照射肿瘤30 min。大肿瘤（~ 16mm）有效消融（100%），90天无复发。所有治愈的大鼠在长达12个月的时间里都拒绝了肿瘤的再次攻击。在双瘤模型中，局部大肿瘤（~ 16mm）的治疗也通过适应性免疫激活治愈了未治疗的肿瘤（4 ~ 6mm）。这是我们第一次证明用PTX前药局部治疗可以产生全身抗肿瘤作用。进一步的研究是必要的，以了解机制和最佳条件，以实现临床可翻译的全身抗肿瘤作用。
We demonstrated that a large primary and a small untreated distant breast cancer could be controlled by local treatment with our light-activatable paclitaxel (PTX) prodrug. We hypothesized that the treated tumor would be damaged by the combinational effects of photodynamic therapy (PDT) and locally released PTX and that the distant tumor would be suppressed by systemic antitumor effects. Syngeneic rat breast cancer models (single- and two-tumor models) were established on Fischer 344 rats by subcutaneous injection of MAT B III cells. The rats were injected with PTX prodrug (dose: 1 umole kg−1, i.v.), and tumors were treated with illumination using a 690-nm laser (75 or 140 mW cm−1 for 30 min, cylindrical light diffuser, drug-light interval [DLI] 9 h). Larger tumors (~16 mm) were effectively ablated (100%) without recurrence for >90 days. All cured rats rejected rechallenged tumor for up to 12 months. In the two-tumor model, the treatment of the local large tumor (~16 mm) also cured the untreated tumor (4–6 mm) through adaptive immune activation. This is our first demonstration that local treatment with our PTX prodrug produces systemic antitumor effects. Further investigations are warranted to understand mechanisms and optimal conditions to achieve clinically translatable systemic antitumor effects.
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影响因子：
3.4
作者：
Chakraborty A;Held KD;Prise KM;Liber HL;Redmond RW
通讯作者：
Redmond RW
DOI：
10.3322/caac.20114
发表时间：
2011-07
期刊：
CA: a cancer journal for clinicians
影响因子：
--
作者：
Agostinis P;Berg K;Cengel KA;Foster TH;Girotti AW;Gollnick SO;Hahn SM;Hamblin MR;Juzeniene A;Kessel D;Korbelik M;Moan J;Mroz P;Nowis D;Piette J;Wilson BC;Golab J
通讯作者：
Golab J
影响因子：
3.8
作者：
Baran, Timothy M.;Foster, Thomas H.
通讯作者：
Foster, Thomas H.
远红色的光线可激活，多功能前药，用于荧光光学成像和组合处理。
影响因子：
7.3
作者：
Bio M;Rajaputra P;Nkepang G;You Y
通讯作者：
You Y
影响因子：
4.9
作者：
Bio, Moses;Nkepang, Gregory;You, Youngjae
通讯作者：
You, Youngjae