Correlation of hypoxia status with radiosensitizing effects of sodium glycididazole: A preclinical study

Abstract

The correlation of pretreatment hypoxia status with the radiosensitization effect of sodium glycididazole (CMNa) was not previously defined. The purpose of the present study was to evaluate the tumor hypoxia status in various cancer xenografts and to investigate the correlation between tumor hypoxia status and radiosensitizing effects of CMNa based on the pharmacokinetic and pharmacodynamic parameters. Human esophageal cancer (EC109), head and neck cancer (FaDu) and lung cancer (A549) nude mice xenografts were used. The concentrations of CMNa and its metabolites in the tumors and normal tissues were determined by high-performance liquid chromatography following intravenous injection of 171.9, 57.3 or 19.1 mg/kg CMNa. The tumors were irradiated with 30 Gy in 6 fractions with CMNa administration prior to each irradiation. The tumor growth delay values were calculated for each treatment group and compared with groups treated with radiation alone. Tumor hypoxia status was verified by immunohistostaining of tissues for hypoxia inducible factor 1α (HIF-1α) staining, and the concentration of plasma osteopontin (OPN) was determined using ELISA. The correlation between OPN concentration and tumor growth delay was subsequently analyzed. It was observed that the drug concentration in the tumor was 1.6-2.8 times higher compared with adjacent muscle, particularly at high and medium doses. CMNa was able to sensitize tumors to irradiation, particularly for EC109 and FaDu xenografts at high dose (P<0.05). Furthermore, there was markedly increased expression of HIF-1α and plasma OPN levels in FaDu and EC109 xenografts compared with A549. Additionally, it was indicated that pretreatment hypoxia status might be correlated with the radiosensitizing effects of CMNa. The present data demonstrated that tumor hypoxia status might be correlated with the radiosensitizing effects of CMNa in different tumor models.

A preclinical study: correlation between PD-L1 PET imaging and the prediction of therapy efficacy of MC38 tumor with 68Ga-labeled PD-L1 targeted nanobody

“…The tumors were measured with a digital caliper (volume=length×width×width×0.5) [ 16 ]. As described in our previous study [ 17 ], the relative tumor volume (RTV) was calculated as follows: RTV = Vt / V 0 , where Vt is the volume at any given time and V 0 is the initial volume before treatment. The RTV values were recorded every two days, and the tumor growth delay curve was analyzed.…”

TGIF1 plays a carcinogenic role in esophageal squamous cell carcinoma through the Wnt/β‑catenin and Akt/mTOR signaling pathways

“…When the volumes of the tumors reached approximately 100-150 mm 3 , the tumor growth delay experiment was performed. As described in a previous study by the authors (20), the relative tumor volume (RTV; RTV = Vt/V0, where Vt is the volume of the tumor at any given time and V0 is the initial volume before treatment) was calculated and the growth curve was analyzed. The mice were euthanized by pentobarbital (100 mg/kg) followed by cervical dislocation at 20 days post-injection or when the tumor volume had reached 2,000 mm 3 .…”

Nimotuzumab, an EGFR‑targeted antibody, promotes radiosensitivity of recurrent esophageal squamous cell carcinoma

“…To generate tumor xenografts, the right hind legs of the mice were subcutaneously injected with 4x10 6 EC109 cells or 1x10 7 TE-1 cells. The tumors were measured with a digital caliper in three orthogonal dimensions (a, b and c), and the volume of tumor was calculated as πabc/6 (21). When the volume of tumors reached ~150 mm 3 , the tumor growth delay assay was performed.…”

“…Radiation therapy began 6 h after drug treatment. As described in our previous study (21), the relative tumor volume (RTV) was calculated as follows: RTV = Vt / V 0 , where Vt is the volume of tumor at any given time and V 0 is the initial volume before treatment. The RTV values were recorded and the tumor growth delay curve was analyzed.…”

“…Immunohistochemistry and immunofluorescence staining. Immunohistochemistry was performed as described previously (21). The mice were sacrificed by pentobarbital (100 mg/kg) followed by cervical dislocation, then half of the tumors were removed quickly, embedded in optimal cutting medium (OCT 4583; Sakura Finetek) and frozen until use in immunofluorescence experiments.…”