Glioblastoma (GBM) is the most common and malignant Grade IV primary craniocerebral tumor caused by glial cell carcinogenesis with an extremely poor median survival of 12–18 months. The current standard treatments for GBM, including surgical resection followed by chemotherapy and radiotherapy, fail to substantially prolong survival outcomes. Adeno-associated virus (AAV)-mediated gene therapy has recently attracted considerable interest because of its relatively low cytotoxicity, poor immunogenicity, broad tissue tropism, and long-term stable transgene expression. Furthermore, a range of gene therapy trials using AAV as vehicles are being investigated to thwart deadly GBM in mice models. At present, AAV is delivered to the brain by local injection, intracerebroventricular (ICV) injection, or systematic injection to treat experimental GBM mice model. In this review, we summarized the experimental trials of AAV-based gene therapy as GBM treatment and compared the advantages and disadvantages of different AAV injection approaches. We systematically introduced the prospect of the systematic injection of AAV as an approach for AAV-based gene therapy for GBM.
1 January 2018 in Evidence-Based Complementary and Alternative Medicine
Objective. This study was designed to evaluate the clinical efficacy of combined traditional Chinese medicine (TCM) and conventional chemotherapy versus conventional chemotherapy in patients with stage II‐IIIA non‐small‐cell lung cancer (NSCLC) after radical surgery. Methods. A retrospective cohort study was conducted in patients with stage II‐IIIA NSCLC from Subei People′s Hospital and Yangzhou Traditional Chinese Medicine Hospital in Yangzhou City of Jiangsu Province from 2012 to 2016. Patients were divided into two groups: the TCM user group (patients receiving treatment with integrated TCM and conventional chemotherapy) and the non‐TCM user group (patients receiving conventional chemotherapy only). The two groups were compared for their median disease‐free survival (DFS) and median overall survival (OS). Results. A total of 67 patients with stage II‐IIIA NSCLC were enrolled between January 2012 and December 2016. The median DFS for the non‐TCM user group was 601 days (95% confidence interval [CI], 375.7‐826.3). The median DFS for TCM user group could not be calculated. However, log‐rank analysis showed that the median survival time in the TCM user group was significantly longer than that of the non‐TCM user group (P < 0.05). In addition, several significant risk factors were detected for predicting disease prognosis in patients with NSCLC, such as age, ECOG, lymphatic metastasis, and body mass index (BMI). For patients harboring these independent risk factors, the DFS of TCM user group was much longer than that of non‐TCM user group (P < 0.05). Conclusion. Adjuvant therapy with TCM may reduce the rate of tumor recurrence and metastasis and prolong DFS of patients with stage II‐IIIA NSCLC.
22 September 2006 in European Journal of Nuclear Medicine and Molecular Imaging
Background: Antiangiogenic agent-treated patients usually develop cavitation in their lung lesions. The clinical significance of lung cavitation development during antiangiogenic therapy has not been determined yet. Herein, we evaluated the clinical outcomes of patients who developed tumor cavitation following apatinib treatment and explored the mechanisms. Methods: In this study (Clinical Trial No. NCT03629691), 187 patients (77 lung cancer and 110 gastric adenocarcinoma patients) who had progressed or relapsed after undergoing at least two lines of systemic therapy in accordance with the NCCN guidelines for primary or metastatic lung tumors were treated with apatinib at a dosage of 250 mg per day between February 1, 2015 and May 19, 2017. The effect of lung cavitation development on locoregional control (LRC), progression-free survival (PFS), and overall survival (OS) was analyzed with Kaplan-Meier estimates and compared with the log-rank test. Zebrafish experiments were used to study the anticancer mechanism of apatinib in different tumors. Western-blotting was used to analyze the expression of Cyclin D1, p53, HIF-α, and VEGFR before and after apatinib treatment in both normoxia and hypoxia. Results: Cavitation development was beneficial in patients receiving apatinib therapy regardless of whether they had primary or metastatic lung cancer. Zebrafish experiments showed that apatinib inhibited tumor growth by both suppressing vascular growth and inhibiting cell proliferation. Vascular proliferation induced by the H1299 cell lines showed higher sensitivity to apatinib than that induced by the SCG-7901 cell line. However, apatinib showed weak tumor type selectivity on cell proliferation inhibition in vivo. Under hypoxic conditions, apatinib could not inhibit the protein expression of VEGFR and HIF-α in both cell lines; however, apatinib decreased the expression of cyclin D1 and P53 significantly. Conclusions: Lung cavitation development is common with apatinib therapy and is a potential prognostic marker. Apatinib inhibits tumor growth by both vessel growth inhibition and proliferation inhibition.