OBJECTIVESTreatment-induced lesions represent a great challenge in neuro-oncology. The aims of this study were (i) to characterize treatment induced lesions in glioblastoma patients treated with chemoradiotherapy and heat-shock protein (HSP) vaccine and (ii) to evaluate the diagnostic accuracy of diffusion weighted imaging for differentiation between treatment-induced lesions and tumor progression.METHODSTwenty-seven patients with newly diagnosed glioblastoma treated with HSP vaccine and chemoradiotherapy were included. Serial magnetic resonance imaging evaluation was performed to detect treatment-induced lesions and assess their growth. Quantitative analysis of the apparent diffusion coefficient (ADC) was performed to discriminate treatment-induced lesions from tumor progression. Mann-Whitney U-test and receiver operating characteristic (ROC) curves were used for analysis.RESULTSThirty-three percent of patients developed treatment-induced lesions. Five treatment-related lesions appeared between end of radiotherapy and the first vaccine administration; 4 lesions within the first 4 months from vaccine initiation and 1 at 3.5 years. Three patients with pathology proven treatment-induced lesions showed a biphasic growth pattern progressed shortly after. ADC ratio between the peripheral enhancing rim and central necrosis showed an accuracy of 0.84 (95% CI 0.63-1) for differentiation between progression and treatment-induced lesions.CONCLUSIONOur findings do not support the iRANO recommendation of a 6-month time window in which progressive disease should not be declared after immunotherapy initiation. A biphasic growth pattern of pathologically proven treatment-induced lesions was associated with a dismal prognosis. The presence of lower ADC values in the central necrotic portion of the lesions compared to the enhancing rim shows high specificity for detection of treatment-induced lesions.

2019-08-01·Advanced Healthcare Materials2区 · 材料科学

Biomodal Tumor‐Targeted and Redox‐Responsive Bi₂Se₃ Hollow Nanocubes for MSOT/CT Imaging Guided Synergistic Low‐Temperature Photothermal Radiotherapy

2区 · 材料科学

Article

作者: Li, Nan ; Wang, Siyu ; Cheng, Yu ; Wang, Yidan ; Tan, Fengping ; Zhu, Yan ; Lian, Fan ; Wang, Yule ; Song, Yilin

AbstractHyperthemia (>50 °C) induced heating damage of nearby normal organs and inflammatory diseases are the main challenges for photothermal therapy (PTT) of cancers. To overcome this limitation, a redox‐responsive biomodal tumor‐targeted nanoplatform is synthesized, which can achieve multispectral optoacoustic tomography/X‐ray computed tomography imaging‐guided low‐temperature photothermal‐radio combined therapy (PTT RT). In this study, Bi2Se3 hollow nanocubes (HNCs) are first fabricated based on a mild cation exchange way and Kirkendall effect and then modified with hyaluronic acid (HA) through redox‐cleavable linkage (‐s‐s‐), thus enabling the HNC to target cancer cells overexpressing CD‐44 and control the cargo release profile. Finally, gambogic acid (GA), a type of heat‐shock protein (HSP) inhibitor, which is vital to cells resisting heating‐caused damage is loaded, into Bi2Se3 HNC. Such HNC‐s‐s‐HA/GA under a mild NIR laser irradiation can induce efficient cancer cell apoptosis, achieving PTT under relatively low temperature (≈43 °C) with remarkable cancer cell damage efficiency. Furthermore, enhanced radiotherapy (RT) can also be experienced without depth limitation based on RT sensitizer Bi2Se3 HNC. This research designs a facile way to synthesize Bi2Se3 HNC‐s‐s‐HA/GA possessing theranostic functionality and cancer cells‐specific GSH, but also shows a low‐temperature PTT RT method to cure tumors in a minimally invasive and highly efficient way.

2019-02-20·ACS Applied Materials & Interfaces2区 · 材料科学

Biocompatible Heat-Shock Protein Inhibitor-Delivered Flowerlike Short-Wave Infrared Nanoprobe for Mild Temperature-Driven Highly Efficient Tumor Ablation

2区 · 材料科学

Article

作者: Liu, Yuxin ; Jiang, Anqi ; Ma, Liyi ; Zhai, Xuejiao ; Zhou, Jing ; Mao, Fang ; Liu, Lidong

Multifunctional nanomaterials for dual-mode imaging guided cancer therapy are highly desirable in clinical applications. Herein, a flowerlike NiS₂-coated NaLuF₄:Nd (Lu:Nd@NiS₂) nanoparticle was synthesized as a novel therapeutic agent for short-wave infrared light imaging and magnetic resonance imaging to guide photothermal therapy (PTT). The material was then loaded with phenolic epigallocatechin 3-gallate (EGCG), which is a natural heat-shock protein 90 (HSP90) inhibitor. Upon near infrared irradiation, EGCG was released from the Lu:Nd@NiS₂-EGCG, which bound HSP90 and reduced cell tolerance to heat, resulting in a better therapeutic effect at the same elevated temperature. Therefore, with minimal side effects and remarkable antitumor efficacy in vivo, Lu:Nd@NiS₂-EGCG appeared to be a promising photothermal agent for enhanced PTT.

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