Efficacy and safety of tumor-treating fields in treatment of high-grade gliomas / 中华神经医学杂志

Objective:Tumor-treating fields (TTFields) is a kind of non-invasive anti-mitotic tumor therapy, which has been approved for patients with newly diagnosed and recurrent glioblastoma. This study aims to explore the efficacy and safety of TTFields in high-grade gliomas in clinical practice settings.Methods:The clinical data of 15 patients with recurrent glioma and 9 patients with newly diagnosed high-grade glioma admitted to our center from April 2019 to January 2021 were retrospectively analyzed. All patients accepted TTFields≥1 month. Follow-up was performed for 5.3 months (ranged from 2.3 to 10.7 months); Response Assessment in Neuro-Oncology Working Group (RANO) criteria was used to evaluate the glioma responses. The progression-free survival (PFS) and overall survival (OS) were calculated according to Kaplan-Meier method. Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0) and TTFields related skin adverse reaction (dAE) criteria were used to evaluate the adverse events. Quality of life questionnaire-core 30 (QLQ-C30) and QLQ-brain cancer module (QLQ-BN20) questionnaires were used to evaluate the health-related quality of life (HRQoL). Treatment compliance was evaluated by data on the use of NovoTTF-200A devices, and calculated as a percentage of daily TTFields usage.Results:The median duration of TTFields was 4.2 months (ranged from 1.0 to 10.7 months), with a median compliance rate of 91.5% (67.0%-97.0%). TTFields was used alone in 2 patients and used with combination of chemotherapy in 22 patients. From follow-up to April 2021, 14 patients had stable symptoms and 10 had disease progression (8 died). The median PFS and OS of recurrent patients were 5.9 months ( 95%CI: 3.3-8.6 months) and 8.5 months ( 95%CI: 3.2-13.8 months), respectively; and the median PFS and OS of newly diagnosed patients were both 10.7 months (without 95%CI). The common adverse events included grading 1 dAE (58.3%) and grading 2 dAE (12.5%), without grading 3 or 4 dAE, manifested as contact or allergic dermatitis, erosion, folliculitis and ulcers. And 87.5% patients had stable HRQoL. Conclusions:The preliminary results showed that the survival of recurrent high-grade glioma patients treated by TTFields is similar to that reported in foreign literature; and the newly diagnosed patients need further survival follow-up. The patients' treatment compliance and safety are good. The dAE incidence (grading 1-2) is higher than that reported in the literature, and the toxicity was acceptable.

Primary central nervous system lymphoma and glioblastoma image differentiation based on sparse representation system / 生物医学工程学杂志

It is of great clinical significance in the differential diagnosis of primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM) because there are enormous differences between them in terms of therapeutic regimens. In this paper, we propose a system based on sparse representation for automatic classification of PCNSL and GBM. The proposed system distinguishes the two tumors by using of the different texture detail information of the two tumors on T1 contrast magnetic resonance imaging (MRI) images. First, inspired by the process of radiomics, we designed a dictionary learning and sparse representation-based method to extract texture information, and with this approach, the tumors with different volume and shape were transformed into 968 quantitative texture features. Next, aiming at the problem of the redundancy in the extracted features, feature selection based on iterative sparse representation was set up to select some key texture features with high stability and discrimination. Finally, the selected key features are used for differentiation based on sparse representation classification (SRC) method. By using ten-fold cross-validation method, the differentiation based on the proposed approach presents accuracy of 96.36%, sensitivity 96.30%, and specificity 96.43%. Experimental results show that our approach not only effectively distinguish the two tumors but also has strong robustness in practical application since it avoids the process of parameter extraction on advanced MRI images.

Assessment of chemoradiotherapy response in glioma with magnetic resonance amide proton transfer imaging in a rodent model.

Magnetic resonance amide proton transfer (APT) imaging has proved its potential for detecting tumors and evaluating treatment response by depicting chemical exchange saturation transfer effect between the endogenous protein/peptide amide proton and bulk water. However, conventional asymmetry analysis for APT effect measurement is susceptible to concomitant contributions, particular semisolid magnetic transfer (MT) and nuclear overhauser effect. In this study, dominant saturation transfer (ST) effects, including direct water saturation and MT, were estimated from a sum of two Lorentzian functions. APT effect was then quantified by subtracting the Z-spectrum with the two ST effects. Feasibility of the method in the assessment of glioma therapeutic response was investigated in a rodent model at 3 Tesla.

The study on Notch1 pathway-related tubular formation of glioma cell lines / 中国神经精神疾病杂志

Objective To explore the mechanism of the formation of glioma cells derived vessels (GCDV).Methods The tubular formation assay was performed on 3D cell cultures of U87,U251,U373,SF295,T98G,SKMG-4 and C6 glioma cell lines.The expression of Notch1 、Dll4 were examined by western blot analysis.Result The mean number of vasculogenic channels of cell lines C6,U373,U87,T98G,SF295,U251 and SKMG-4 per area (100×) were 25.2±5.0,36.4±3.2,19.0±2.2,12.6±2.4,4±2.2,0.2±0.4 and 0,respectively.The relative protein densities of Notchl in U87,U251,T98G,SF295,SKMG-4,C6 and U373 were 0.34,0.21,0.79,0.04,0.28,1.75 and 1.19,which were significantly related with the tubular formation ability (P＜0.05).However,the expression of Dll4 was not associated with tubular formation ability (P＞0.05).Conclusion Notch1 may play a key role in tubular formation of glioma cells while the role of Dll4 in the process needs further study.

A new aurone glycoside from Veratrum dahuricum (Turcz.) Loes. f / 药学学报

To study the chemical constituents of Veratrum dahuricum (Turcz.) Loes. f., a new aurone glycoside named as (Z)-7, 4'-dimethoxy-6-hydroxyl-aurone-4-O-β-glucopyranoside was isolated from the 95% ethanol extracts of the rhizomes and roots of Veratrum dahuricum (Turcz.) Loes. f. by repeated column chromatography on silica gel and recrystallization. Its structure was established by extensive spectroscopic analyses, and its cytotoxicities against HepG-2, MCF7 and A549 cell lines were measured in vitro.

Part IV. Synthesis and antitumor evaluation of s-triazolothiadiazines and pyrazolo s-triazoles derived from ciproxacin / 药学学报

An efficient modified route based on the targeting mechanism of antibacterial fluoroquinolones for the shift from the antibacterial activity to the antitumor one was further developed. Using a fused heterocyclic ring, s-triazolothiadiazine as a carboxyl bioisostere of ciprofloxacin, the title compounds, 1-cyclopropyl-6-fluoro-7-piperazin-1-yl-3-(6-substituted-phenyl-7H-[1, 2, 4]triazolo[3, 4-b][1, 3, 4]thiadiazin-3-yl)-quinolin-4(1H)-ones (5a-5e) and their corresponding N-acetyl products (6a-6e), were designed and synthesized, separately. Meaningfully, a ring-contraction of fused six-membered thiadiazine occurred by a sulfur extrusion reaction gave new tri-acetylated fused heterocycles related to pyrazolo[5, 1-c][1, 2, 4] triazoles (7a-7e). The in vitro antitumor activity against L1210, CHO and HL60 cell lines was also evaluated for the synthesized fifteen heterocycles compared to parent ciprofloxacin by methylthiazole trazolium (MTT) assay. Interestingly, the results displayed that fifteen fused heterocyclic compounds showed more significant growth inhibitory activity (IC50 150.0 micromol x L(-1)), and the active order decreased from 7a-7e to 5a-5e to 6a-6e, respective.