PEGylation prolongs the blood circulation time of drugs; however, it simultaneously reduces the tumor penetration of drugs due to the nonfouling function and bulky hydrodynamic volume of PEG, leading to unsatisfactory outcomes in the treatment of solid tumors. Herein, we report the in situ growth of a bioreducible polymer of poly(N-oxide) from an important protein drug of interferon alpha (IFN) to generate site-specific IFN−poly(N-oxide) conjugates with higher bioactivity than a clinically used PEGylated IFN of PEGASYS. An IFN−poly(Noxide) conjugate is screened out to have a circulating half-life as long as 51 h, which is similar to that of PEGASYS but 96-fold greater than that of IFN. However, the conjugate greatly outperforms PEGASYS and IFN in tumor penetration and antitumor efficacy in mice bearing melanoma. This enhanced tumor penetration is ascribed to the adsorption-mediated transcytosis of the conjugate whose poly(N-oxide) is biologically reduced into poly(tertiary amine), under hypoxia, which can be further protonated in the acidic tumor microenvironment. These novel findings demonstrate that poly(N-oxide)s are not only longcirculating but also bioreducible under hypoxia and are of great promise as next-generation carriers to deliver drugs into the interior of solid tumors to enhance their antitumor efficacy.
Background. The aim of this study was to evaluate quality of life of free anterolateral thigh flap (ALTFF) for reconstruction of tissue defects of total or near-total glossectomy. Methods. Quality of life was assessed by means of the University of Washington Quality of Life (UW-QOL) and the 14-item Oral Health Impact Profile (OHIP-14), after 12 months postoperatively. Results. 65 of 79 questionnaires were returned (82.27%). In the UW-QOL, the best-scoring domain was “shoulder,” whereas the lowest scores were for “chewing” and “pain.” In the OHIP-14, the lowest-scoring domain was “handicap,” followed by “Social disability” and “Psychological disability.” Conclusion. Free anterolateral thigh perforator flaps for reconstruction of total or near-total glossectomy defects after cancer resection would have significantly influenced the patients’ oral functions and quality of life.
Oral squamous cell carcinoma (OSCC) is a common malignant cancer with unfavorable prognosis, and the epithelial‐to‐mesenchymal transition (EMT) is a critical contributor to OSCC metastasis. Recently, we have shown that sirtuin 7 (Sirt7) is associated with EMT and OSCC metastasis by acetylating small mother against decapentaplegic 4 (Smad4). Nonetheless, the mechanism of Sirt7 downregulation in OSCC cells remains unknown. This study analyzed the potential microRNAs that were predicted to regulate Sirt7 expression by online databases. We identified miR‐770 as an upstream regulator of Sirt7 that targets its 3′‐untranslated region. The expression of miR‐770 was observed to be negatively correlated with the mRNA expression of Sirt7 in metastatic OSCC tumors, and higher miR‐770 expression was correlated with poorer OSCC patient survival. Our in vitro data indicated that miR‐770 promoted OSCC cell migration and invasion, and this process was dependent on Sirt7/Smad4 signaling. Furthermore, in vivo metastasis experiments indicated that miR‐770 overexpression led to more prominent OSCC metastasis and downregulated Sirt7 expression. Collectively, our results revealed a new role of Sirt7 downregulation in metastatic OSCC and suggested that miR‐770 is a potential target in counteracting OSCC metastasis.
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