Ultrasmall zirconium carbide nanodots for synergistic photothermal-radiotherapy of glioma.

Glioma is characterized by highly invasive, progressive, and lethal features. In addition, conventional treatments have been poorly effective in treating glioma. To overcome this challenge, synergistic therapies combining radiotherapy (RT) with photothermal therapy (PTT) have been proposed and extensively explored as a highly feasible cancer treatment strategy. Herein, ultrasmall zirconium carbide (ZrC) nanodots were successfully synthesized with high near-infrared absorption and strong photon attenuation for synergistic PTT-RT of glioma. ZrC-PVP nanodots with an average size of approximately 4.36 nm were prepared by the liquid exfoliation method and modified with the surfactant polyvinylpyrrolidone (PVP), with a satisfactory absorption and photothermal conversion efficiency (53.4%) in the near-infrared region. Furthermore, ZrC-PVP nanodots can also act as radiosensitizers to kill residual tumor cells after mild PTT due to their excellent photon attenuating ability, thus achieving a significant synergistic therapeutic effect by combining RT and PTT. Most importantly, both in vitro and in vivo experimental results further validate the high biosafety of ZrC-PVP NDs at the injected dose. This work systematically evaluates the feasibility of ZrC-PVP NDs for glioma treatment and provides evidence of the application of zirconium-based nanomaterials in photothermal radiotherapy.

DAB2IP predicts treatment response and prognosis of ESCC patients and modulates its radiosensitivity through enhancing IR-induced activation of the ASK1-JNK pathway.

BACKGROUND: Disabled homolog 2 interacting protein (DAB2IP) plays a tumor-suppressive role in several types of human cancers. However, the molecular status and function of the DAB2IP gene in esophageal squamous cell carcinoma (ESCC) patients who received definitive chemoradiotherapy is rarely reported. METHODS: We examined the expression dynamics of DAB2IP by immunohistochemistry (IHC) in 140 ESCC patients treated with definitive chemoradiotherapy. A series of in vivo and in vitro experiments were performed to elucidate the effect of DAB2IP on the chemoradiotherapy (CRT) response and its underlying mechanisms in ESCC. RESULTS: Decreased expression of DAB2IP in ESCCs correlated positively with ESCC resistance to CRT and was a strong and independent predictor for short disease-specific survival (DSS) of ESCC patients. Furthermore, the therapeutic sensitivity of CRT was substantially increased by ectopic overexpression of DAB2IP in ESCC cells. In addition, knockdown of DAB2IP dramatically enhanced resistance to CRT in ESCC. Finally, we demonstrated that DAB2IP regulates ESCC cell radiosensitivity through enhancing ionizing radiation (IR)-induced activation of the ASK1-JNK signaling pathway. CONCLUSIONS: Our data highlight the molecular etiology and clinical significance of DAB2IP in ESCC, which may represent a new therapeutic strategy to improve therapy and survival for ESCC patients.

Mapping of Cervical and Upper Mediastinal Lymph Node Recurrence for Guiding Clinical Target Delineation of Postoperative Radiotherapy in Thoracic Esophageal Squamous Cell Carcinoma.

BACKGROUND: The lower neck and upper mediastinum are the major regions for postoperative radiotherapy (PORT) in thoracic esophageal squamous cell carcinoma (TESCC). However, there is no uniform standard regarding the delineation of nodal clinical target volume (CTVnd). This study aimed to map the recurrent lymph nodes in the cervical and upper mediastinal regions and explore a reasonable CTVnd for PORT in TESCC. METHODS: We retrospectively reviewed patients in our hospital with first cervical and/or upper mediastinal lymph node recurrence (LNR) after upfront esophagectomy. All of these recurrent lymph nodes were plotted on template computed tomography (CT) images with reference to surrounding structures. The recurrence frequency at different stations was investigated and the anatomic distribution of recurrent lymph nodes was analyzed. RESULTS: A total of 119 patients with 215 recurrent lymph nodes were identified. There were 47 (39.5%) patients with cervical LNR and 102 (85.7%) patients with upper mediastinal LNR. The high-risk regions were station 101L/R, station 104L/R, station 106recL/R, station 105 and station 106pre for upper TESCC and station 104L/R, station 106recL/R, station 105, station 106pre and station 106tbL for middle and lower TESCCs. LNR in the external group of station 104L/R was not common, and LNR was not found in the narrow spaces where the trachea was in close contact with the innominate artery, aortic arch and mediastinal pleura. LNR below the level of the cephalic margin of the superior vena cava was also not common for upper TESCC. CONCLUSIONS: The CTVnd of PORT in the cervical and upper mediastinal regions should cover station 101L/R, station 104L/R, station 106recL/R, station 105 and station 106pre for upper TESCC and station 104L/R, station 106recL/R, station 105, station 106pre and station 106tbL for middle and lower TESCCs. Based on our results, we proposed a useful atlas for guiding the delineation of CTVnd in TESCC.