Fighting against Drug-Resistant Tumor by the Induction of Excessive Mitophagy with Transferrin Nanomedicine.

The effectiveness of chemotherapy is primarily hindered by drug resistance, and autophagy plays a crucial role in overcoming this resistance. In this project, a human transferrin nanomedicine contains quercetin (a drug to induce excessive autophagy) and doxorubicin is developed (HTf@DOX/Qu NPs). The purpose of this nanomedicine is to enhance mitophagy and combating drug-resistant cancer. Through in vitro studies, it is demonstrated that HTf@DOX/Qu NPs can effectively downregulate cyclooxygenase-2 (COX-2), leading to an excessive promotion of mitophagy and subsequent mitochondrial dysfunction via the PENT-induced putative kinase 1 (PINK1)/Parkin axis. Additionally, HTf@DOX/Qu NPs can upregulate proapoptotic proteins to induce cellular apoptosis, thereby effectively reversing drug resistance. Furthermore, in vivo results have shown that HTf@DOX/Qu NPs exhibit prolonged circulation in the bloodstream, enhanced drug accumulation in tumors, and superior therapeutic efficacy compared to individual chemotherapy in a drug-resistant tumor model. This study presents a promising strategy for combating multidrug-resistant cancers by exacerbating mitophagy through the use of transferrin nanoparticles.

Radiotherapy for patients with esophageal cancer aged 80 years or older: A 16-year experience.

PURPOSE: Radiotherapy (RT) plays an important role in esophageal cancer (EC) patients aged ≥80 years. However, the survival modality and prognostic factors remain poorly understood. Thus, this study aimed to evaluate the tolerance and long-term overall survival (OS) of patients aged ≥80 years who were diagnosed with EC and underwent definitive RT. MATERIALS AND METHODS: A total of 213 consecutive patients with EC over 80 years old who were treated with curative intent RT between February 1999 and December 2015 at our institution were retrospectively reviewed. The clinical prognostic variables were analyzed against OS in univariate analyses using log-rank tests and in a multivariate model using Cox regression proportional hazards analysis. RESULT: The median patient age was 82 (range: 80-94) years. Atotal of 192 patients (90.1%) completed the definitive RT (median: 60 Gy, range: 50-72 Gy), and 11 patients had grade 4 or higher acute toxicity, including esophagitis, a cardiac event, infections, and sudden death. Atotal of 168 deaths (78.9%) were observed with a median follow up of 47 months (range: 0-153 months). The OS rates were 50.3%, 17.6%, and 13.2% at 1, 3, and 5 years, respectively. Multivariable analysis identified that tumors located in the cervical and upper thorax, a shorter tumor lesion, RT treatment of 50-60Gy, and a better response to treatment were the factors associated with longer OS. CONCLUSION: Definitive RT could be considered as an effective treatment for patients with EC who are older than 80 years, and 50-60 Gy seems to be a reasonable dose for these patients.

Polyethylene glycol-derived polyelectrolyte-protein nanoclusters for protein drug delivery.

Polyelectrolyte-protein nanocomplexes prepared under mild and simple conditions which could have biological activity arising from protein have emerged as fascinating protein delivery systems. However, common polyelectrolytes have problems of biocompatibility and metabolism in vivo, which may limit their further applications. Herein, a novel polyethylene glycol polyelectrolyte was synthesized and used for carrying protein drugs. Different from previously reported polyelectrolyte-protein nanoclusters, the polyethylene glycol polyelectrolyte-protein nanoclusters avoid organic solvent and protein modification, and the structure and bioactivity of proteins are well preserved. Moreover, the polyethylene glycol polyelectrolyte-protein nanoclusters have good hemocompatibility and biocompatibility. These novel polyethylene glycol polyelectrolyte-protein nanoclusters would provide a potent tool for fabrication of versatile protein drug carriers.

Distribution of Peripheral Blood Cells in Esophageal Cancer Patients During Concurrent Chemoradiotherapy Predicts Long-Term Locoregional Progression Hazard After Treatment (GASTO1072).

PURPOSE: Predicting the response to chemoradiotherapy is critical for the optimal management of esophageal cancer; however, it remains an unmet clinical need. This study aimed to evaluate the predictive potential of peri-treatment peripheral blood cells (PBC) in disease progression hazard in esophageal cancer following chemoradiotherapy. PATIENTS AND METHODS: A total of 87 patients with primary esophageal squamous cell carcinoma were subjected to definitive concurrent chemoradiotherapy in a Phase II trial. PBC parameters (hemoglobin, neutrophils, platelets, lymphocytes, and monocytes) were collected at seven time points throughout the course of radiotherapy. The potential of peri-treatment PBC parameters to predict the 3-year cumulative hazard of tumor progression was evaluated. RESULTS: Patients with disease progression displayed distinct distribution patterns of peri-treatment PBC compared to that in patients without disease progression. Greater prediction capabilities for risk of locoregional disease progression were found in PBC collected after the start of radiotherapy compared to those in their pretreatment counterparts, and in individual parameters rather than cell-to-cell ratios. The most predictive PBC parameters were integrated by summation and designated as a PBC score (PBCS), which further augmented their predictive power. Patients classified according to their PBCS (high vs medium v. low) had significantly different 3-year cumulative hazards of locoregional progression (58% vs 29% vs 7%, P = 0.0017). Multivariate analysis confirmed that high PBCS (HR, 12.2; 95% CI, 2.0-76.3; P = 0.007) and medium (HR, 5.8; 95% CI 1.2-27.7; P = 0.028) were independent indicators of locoregional progression. CONCLUSION: Systematic analysis of PBC distribution in esophageal cancer patients undergoing definitive chemoradiotherapy could help predict long-term locoregional progression hazard after treatment.