Photodynamic therapy (PDT) kills cancer cells by converting tumour oxygen into reactive singlet oxygen (1O2) using a photosensitizer. However, pre-existing hypoxia in tumours and oxygen consumption during PDT can result in an inadequate oxygen supply, which in turn hampers photodynamic efficacy. Here to overcome this problem, we create oxygen self-enriching photodynamic therapy (Oxy-PDT) by loading a photosensitizer into perfluorocarbon nanodroplets. Because of the higher oxygen capacity and longer 1O2 lifetime of perfluorocarbon, the photodynamic effect of the loaded photosensitizer is significantly enhanced, as demonstrated by the accelerated generation of 1O2 and elevated cytotoxicity. Following direct injection into tumours, in vivo studies reveal tumour growth inhibition in the Oxy-PDT-treated mice. In addition, a single-dose intravenous injection of Oxy-PDT into tumour-bearing mice significantly inhibits tumour growth, whereas traditional PDT has no effect. Oxy-PDT may enable the enhancement of existing clinical PDT and future PDT design.

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PurposeTo determine the oncogenic role of the sixth subunit of chaperonin-containing tailless complex polypeptide 1 (CCT6A) in hepatocellular carcinoma (HCC) and address the correlation of CCT6A with clinicopathological characteristics and survival. Additionally, this study aimed to explore the effect of CCT6A on HCC cells and the underlying mechanisms.MethodsWe searched for levels of CCT6A expression in the Oncomine database and GEPIA database, which was then validated by analyzing cancer and adjacent non-cancerous tissues of HCC patients using quantitative PCR, Western blot, and immunohistochemistry assays. The relationship between CCT6A expression and survival was analyzed from the GEPIA database and confirmed by immunohistochemistry assays of 133 HCC tissue sections. In addition, the effect of depleting CCT6A on cell proliferation was assessed by CCK-8 and colony formation assays. Cell cycle analysis, immunofluorescence assays, GSEA analysis, and cyclin D expression analyzed by Western blot were used to explore the possible underlying mechanism how dysregulated CCT6A affect the proliferation of HCC.ResultsBoth mRNA and protein levels of CCT6A were increased in HCC tissues. Higher CCT6A expression was significantly associated with reduced overall survival (P = 0.023). CCT6A depletion inhibited cell proliferation and downregulated cyclin D, hindering the G1-to-S phase arrest.ConclusionCCT6A may contribute to HCC cell proliferation by accelerating the G1-to-S transition, as it maintains the expression of cyclin D. CCT6A could be considered an oncogene of HCC and could be used as a prognostic biomarker for HCC.

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Background A growing body of evidence suggests that E2Fs, by regulating gene expression related to cell cycle progression and other cellular processes, play a pivotal role in human cancer. However, the distinct roles of each E2F in the development and treatment of hepatocellular carcinoma (HCC) remain unknown. In the present study, the mRNA expression and prognostic value of different E2Fs in HCC are analyzed. Materials and methods Transcriptional and survival data related to E2F expression in patients with HCC were obtained through ONCOMINE and UALCAN databases. Survival analysis plots were drawn with Kaplan–Meier Plotter. The sequence alteration data for E2Fs were obtained from The Cancer Genome Atlas and c-BioPortal. Gene functional enrichment analyses were performed in Database for Annotation, Visualization and Integrated Discovery. Results The mRNA expression levels of E2F1–E2F8 were all significantly upregulated in HCC patients, and high expression of each E2F was obviously related to poor prognosis. Similarly, the expression of E2Fs showed prognostic prediction value in HCC patients with different cancer stages and pathological grades. Moreover, the mutation rate of E2Fs was relatively high in HCC patients, and the DNA sequence alterations primarily occurred in E2F5, E2F3, and E2F6, which were associated with worse overall survival and disease-free survival in HCC patients. Network analysis confirmed that the expression levels of cell cycle-related genes were mostly affected by E2F mutations. Conclusion High expression of individual E2Fs was associated with poor prognosis in all liver cancer patients. E2Fs may be exploited as good prognostic targets for comprehensive management of HCC patients, but this notion should be further evaluated in clinical studies.

Current techniques for diagnosing glioma are invasive and do not accurately predict prognosis. We developed a novel, non-invasive liquid chip assay to diagnose glioma and predict prognosis. Using this method, we determined the methylation state of the Alu element in cell-free DNA extracted from the serum of 109 glioma patients. Controls included 56 patients with benign intracranial tumors and 50 healthy subjects. Matched tumor tissues were processed for 36 patients. The cfDNA from glioma patients showed lower levels of Alu methylation than the controls (P<0.01). Alu methylation was also lower in high-grade than low-grade gliomas (P<0.01), indicating that Alu methylation correlates negatively with disease severity. Moreover, Alu methylation correlated positively with survival (P<0.01). These findings suggest high-throughput liquid chip could serve as a non-invasive diagnostic assay for glioma.

Nanocarriers like PEGylated liposomes have achieved enhanced drug accumulation in tumors and reduced systemic side effects, but failed to actively release the carried drug into cancer cells. To obtain improved therapeutic efficacy, we designed a novel liposome that was inserted by the amphiphilic agent PEG-IR780-C13 (PIC-Lipo) and encapsulated therapeutic agent doxorubicin (DOX), termed as DOX@PIC-Lipo. Upon NIR laser irradiation, the novel liposomes could generate hyperthermia and facilitate the release of encapsulated DOX from PIC-Lipo, which were confirmed by photothermal curves and the DOX release assay in vitro, respectively. In addition, the enhanced DOX release and sufficient hyperthermia have performed synergetic therapeutic efficacy both in vitro and in vivo. Therefore, DOX@PIC-Lipo might provide an active strategy to release the loaded drug for synergetic chemo-photothermal combined therapy.

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