Hypoxia, a salient feature of most solid tumors, confers invasiveness and resistance to the tumor cells. Oxygen-consumption photodynamic therapy (PDT) suffers from the undesirable impediment of local hypoxia in tumors. Moreover, PDT could further worsen hypoxia. Therefore, developing effective strategies for manipulating hypoxia and improving the effectiveness of PDT has been a focus on antitumor treatment. In this review, the mechanism and relationship of tumor hypoxia and PDT are discussed. Moreover, we highlight recent trends in the field of nanomedicines to modulate hypoxia for enhancing PDT, such as oxygen supply systems, down-regulation of oxygen consumption and hypoxia utilization. Finally, the opportunities and challenges are put forward to facilitate the development and clinical transformation of PDT.

Prodrug-nanoparticles turn the disadvantage of the aggregation-caused quenching effect into an advantage to promote dual-modality PR104A release. Besides, photodynamic therapy-induced hypoxia activates PR104A for high-efficiency synergistic therapy.

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Background and objectiveMoyamoya disease (MMD) is an increasingly recognised cause of stroke, mainly described in East Asia. China is the largest nation in Asia, but few studies reported the epidemiology of MMD, especially at a national level. We aimed to estimate the incidence and prevalence of MMD in China.MethodsWe performed a population-based study using data from the national databases of Urban Basic Medical Insurance between 2013 and 2016, covering approximately 0.50 billion individuals. MMD cases were identified by diagnostic code (International Classification of Diseases, 10th Revision I67.5) or related diagnostic text.ResultsA total of 1987 MMD patients (mean age 44.45±14.30 years, female-to-male ratio 1.12) were identified, representing a national crude incidence of 0.59 (95% CI: 0.49 to 0.68) and a prevalence of 1.01 (95% CI: 0.81 to 1.21) per 100 000 person-years in 2016. Rates were higher in females than in males for the incidence (0.66 vs 0.52) and prevalence (1.05 vs 0.90). And the age-specific rates showed a bimodal distribution, with the highest peak in middle-aged group and the second peak in child group.ConclusionsOur results confirm that MMD is relatively common in East Asians, but the rates in China were lower than those in other East Asian countries such as Japan and Korea. The unique epidemiological features, including a relatively weak female predominance and a shift in the highest peak of incidence from children to adults, revealed new sight into MMD. Further research is expected to explore the potential pathogenesis of MMD.

Background: The purpose of this study was to investigate the incidence of venous thromboembolism (VTE) in epidermal growth factor receptor (EGFR) mutations patients with lung adenocarcinoma, to provide clinical basis for the perioperative prevention and treatment of VTE in patients with lung cancer. Methods: This study included patients with invasive lung adenocarcinoma confirmed by pathology from July 2016 to March 2018 after surgical pulmonectomy in Thoracic Surgery Department of Beijing Chaoyang Hospital. All enrolled patients were tested for relevant gene mutations. All patients were classified as adenocarcinoma subtypes by the 2011 International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS) and European Respiratory Society (ERS). Patients were divided into the VTE group and the control group according to whether VTE occurred postoperatively. Baseline data, gene test results, operative data and tumor pathology data between the two groups were compared.Results: According to the inclusion criteria, a total of 323 patients underwent lung cancer surgery were analyzed in this study, including 148 males and 175 females, aged from 25 to 82 years old. Postoperative VTE occurred in 33 patients, with an incidence of 10.2%. Compared the baseline data, there were significant differences in age and BMI between the two groups, but no significant differences in other indicators. Comparing the results of postoperative genetic tests, the cases

The aim of this study was to establish a novel targeting nanobubble (TNB) conjugated with small interfering RNA (siRNA)‐cyanine 5 (Cy5) and to validate its theranostic ability in vivo. The TNB conjugated with neuroepithelial transforming gene 1 (NET‐1) siRNA‐Cy5 was prepared by thin‐film hydration and mechanical sonication method. A hepatocellular carcinoma (HCC) xenograft model was established by subcutaneously injecting SMMC‐7721 cells in BALB/c nude mice. The NET‐1 siRNA‐conjugated TNB was utilized for accurate contrast‐enhanced ultrasound in vivo imaging, which was enabled by the target ligand GPC‐3 antibody and specific gene transfection with the aid of low‐frequency ultrasound (LFUS) irradiation. BALB/c nude mice bearing tumors were randomized into 5 groups and irradiated with LFUS for 5 min after TNB administration; mice were treated twiceaweek for atotal of 60 d. The mean particle size of TNB was <500 nm. Mice treated with NET‐1 siRNA‐conjugated TNB showed a significant decrease in tumor growth and the highest survival rate. Our findings offer an effective and safe gene vehicle and probe for molecular imaging in vivo. It may improve the early diagnosis and treatment effects of HCC.—Wu, B., Shang, H., Liang, X., Sun, Y., Jing, H., Han, X., Cheng, W. Preparation of novel targeting nanobubbles conjugated with small interfering RNA for concurrent molecular imaging and gene therapy in vivo. FASEB J. 33, 14129‐14136 (2019). http://www.fasebj.org

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Background PTEN is one of the most frequently mutated genes in human cancer. Although the roles of canonical PTEN protein and PTEN isoforms have been extensively explored, the current understanding of PTEN family members cannot fully illustrate the diversity of their roles in biological processes and tumor development. Notably, the function of noncoding RNAs arising from PTEN has been less elucidated. Methods We searched circBase and circInteractome to analyze the potential of PTEN for generating circRNAs. Then, Sanger sequencing, RNase R and Actinomycin D assays were used to verify the ring structure of circPTEN1. In situ hybridization and qRT-PCR were used to determine the level of circPTEN1 in peritumor and tumor tissues of colorectal cancer (CRC). Furthermore, functional experiments, including Transwell assay, 3D multicellular tumor spheroid invasion assay and metastasis models, were performed using circPTEN1 knockdown and overexpression cell lines in vitro and in vivo to investigate the effects of circPTEN1 on tumor metastasis in CRC. Mechanistically, luciferase reporter assay, fluorescence in situ hybridization, electrophoretic mobility shift assay, RNA immunoprecipitation, RNA pull-down and mass spectrometry were executed. Results We identified a circular RNA generated from the PTEN gene, designated circPTEN1, that is frequently downregulated in colorectal cancer, and decreased expression of circPTEN1 predicts poor survival. Low expression of circPTEN1 promotes metastasis in PDX models in vivo and accelerates cancer cell invasion in vitro, whereas overexpression of circPTEN1 reveals opposite roles. Mechanically, we found that circPTEN1 is capable of binding the MH2 domain of Smad4 to disrupt its physical interaction with Smad2/3, which reduces the formation and subsequent nucleus translocation of Smad complexes and consequently suppresses the expression of its downstream genes associated with epithelial-mesenchymal transition upon TGF-β stimulation. Furthermore, we found that eIF4A3 suppresses the cyclization of circPTEN1 by directly binding to the circPTEN1 flanking region. Conclusions Our study uncovered a novel PTEN gene-generated circRNA with a tumor suppression function, and further revealed the mechanism of circPTEN1 in CRC metastasis mediated by TGF-β. The identification of circPTEN1 provides a new direction for PTEN investigation, and elucidation of circPTEN1/TGF-β/Smad signaling may pave the way for the development of a potential therapeutic strategy for the suppression of cancer progression.