Apatinib combined with temozolomide in diffuse midline glioma: a novel and effective therapy.

PURPOSE: Diffuse midline glioma (DMG), H3 K27M-mutant is a type of diffuse high-grade glioma that occurs in the brain midline carrying an extremely poor prognosis under the best efforts of surgery, radiation, and other therapies. For better therapy, we explored the efficacy and toxicity of a novel therapy that combines apatinib and temozolomide in DMG. METHODS: A retrospective analysis of 32 patients with DMG who underwent apatinib plus temozolomide treatment was performed. Apatinib was given 500 mg in adults, 250 mg in pediatric patients once daily. Temozolomide was administered at 200 mg/m2/d according to the standard 5/28 days regimen. The main clinical data included basic information of patients, radiological and pathological characteristics of tumors, treatment, adverse reactions, prognosis. RESULTS: The objective response rate was 24.1%, and the disease control rate was 79.3%. The median PFS of all patients was 5.8 months, and median OS was 10.3 months. A total of 236 cycles of treatment were available for safety assessment and the toxicity of the combination therapy was relatively well tolerated. The most common grade 3 toxicities were myelosuppression including leukopenia (5.08%), neutropenia (4.24%), lymphopenia (2.12%), thrombocytopenia (1.69%) and anemia (1.27%). Grade 4 toxicities included neutropenia (2.12%), thrombocytopenia (2.12%) and proteinuria (1.69%). All the adverse events were relieved after symptomatic treatment or dose reduction. CONCLUSIONS: Apatinib plus temozolomide could be an effective regimen with manageable toxicities and favorable efficacy and may outperform temozolomide monotherapy, particularly in newly diagnosed adults with tumors located outside the pons. The novel therapy deserves further investigation in adult DMG patients.

Research on advanced methods of electrochemiluminescence detection combined with optical imaging analysis for the detection of sulfonamides.

In this study, a novel method that combines electrochemiluminescence (ECL) analysis and digital image processing was developed for the detection of sulfonamides. This method is based on the ECL system of ruthenium terpyridine, with 1 mM tripropylamine as a co-reactant to enhance the performance. Under the optimal conditions comprising a solution of pH 7 and a scanning rate of 0.08 V s-1, the Pt electrode has an excellent linear detection range from 5 µM to 5 mM, with a detection limit of 0.85 µM (S/N = 3). A wireless camera is used to record the light-emitting process. The recordings are processed, and the digital images are extracted using image-processing algorithms implemented in Python to calculate the brightness value of the image, which has a linear relationship with the logarithm of the sulfonamide concentration. Image analysis simplifies and improves the stability of the ECL analysis process, while also increasing the speed of analysis. The results indicate that the method can successfully detect a sulfonamide concentration of 5 µM. Thus, the analysis method of ECL combined with image processing is feasible for the detection of sulfonamides, thereby displaying its potential applicability as a novel method in drug and food safety, for instance, for sulfonamide detection in antibiotics.

Combining therapy with recombinant human endostatin and cytotoxic agents for recurrent disseminated glioblastoma: a retrospective study.

BACKGROUND: The optimal chemotherapeutics of recurrent disseminated glioblastoma has yet to be determined. We analyzed the efficacy and safety of recombinant human endostatin (rh-ES) combined with temozolomide and irinotecan in patients with recurrent disseminated glioblastoma. METHODS: We retrospectively reviewed 30 adult patients with recurrent disseminated glioblastoma treated with this combination chemotherapy at Department of Neuro-Oncology, Sanbo Brain Hospital, Capital Medical University of China from November 2009 to August 2018. Temozolomide was given orally at 200 mg/m2 daily for 5 days and rh-ES was administrated 15 mg/d daily for 14 days of each 28-day treatment cycle. Irinotecan was given intravenously every 2 weeks on a 28-day cycle at 340 mg/m2 or 125 mg/m2 depending on antiepileptic drugs. Primary endpoint was progression-free survival (PFS) at 6 months (6 m-PFS). RESULTS: The 6 m-PFS was 23.3%. The median PFS was 3.2 months. The overall survival rate (OS) at 12 months was 28.6%. The median OS was 6.9 months. Six out of 30 (20%) patients demonstrated partial radiographic response and 11 (36.7%) remained stable. The PFS of the 6 patients who got partial response was 5.8, 6.3, 6.9, 13.6, 15.8 and 16.6 months, respectively, and the median time interval of first response was 4 (range, 2.0-6.6) months. The most common adverse events were hematologic toxicities and gastrointestinal effects. The Grade ≥ 3 adverse event was hematologic toxicities. The adverse events were manageable. CONCLUSIONS: Rh-ES, in combination with cytotoxic drugs, was an alternative effective regimen with manageable toxicities in treatment of recurrent disseminated glioblastoma.

Apatinib Plus Temozolomide: An Effective Salvage Treatment for Recurrent Glioblastoma.

BACKGROUND: Treatment for recurrent glioblastoma is poor, and there is a need for better therapies. Here we retrospectively assessed the efficacy and toxicity of temozolomide plus apatinib, an oral small-molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 in recurrent glioblastoma. MATERIALS AND METHODS: A retrospective analysis of patients with recurrent glioblastoma who underwent apatinib plus temozolomide treatment was performed. Apatinib was given at 500 mg once daily. Temozolomide was administered at 200 mg/m2/d on days 1-5 or 50 mg/m2/d continuous daily according to whether they had experienced temozolomide maintenance treatment before. The main clinical data collected included tumor characteristics, status of MGMT promoter, and IDH mutation, number of relapse, response, survival, adverse reactions, and salvage therapies. RESULTS: From April 2016 to August 2019, thirty-one patients were identified. The objective response rate was 26.3%, and the disease control rate was 84.2%. The progression-free survival (PFS) at 6 months and overall survival (OS) at 12 months were 44.6 and 30.2%. The median PFS and OS were 4.9 and 8.2 months, respectively. Two patients achieved long PFS of 30.9 and 38.7+ months. The median survival time after progression of the patients with or without salvage bevacizumab was 5.1 versus 1.2 months. The most common grade 3 or 4 toxicities were hypertension (5.8%), decreased appetite (5.8%), and thrombocytopenia (4.3%), most of which were resolved after symptomatic treatment or dose reduction. CONCLUSION: Apatinib plus temozolomide is an effective salvage regimen with manageable toxicities for recurrent glioblastoma and could not reduce the sensitivity to bevacizumab.

Design and synthesis of amine-functionalized cellulose with multiple binding sites and their application in CC bond forming reactions.

Straw is a green and promising material in nature. However, as is the case for all other biopolymers, straw have to face the challenge of underutilization thereby resulting in environmental and economic issues. To overcome these drawbacks, the urgent exploitation of straw is needed for its comprehensive utilization. In this paper, we chose cellulose as the straw model to prepare two amine ligands functionalized environmentally-friendly cellulose supported catalyst. The ethylenediamine functionalized cellulose catalyst (ADC) was effective in the reaction of aromatic aldehydes with nitromethane to synthesize nitroalkenes and 1,3­dinitroalkanes. Based on ADC, the diethylenetriamine functionalized cellulose (CL-DETA-Cl) could capture Pd firmly by virtue of the covalent bonding between diethylenetriamine functionalized cellulose and palladium nanoparticles. The synthesized catalyst (CL-DETA-Pd) was then illuminated by using FT-IR, TGA, XRD, TEM, ICP-OES and XPS. The multifunctional complex could catalyze the Suzuki-Miyaura reactions efficiently and prevented the metal leaching through the multiple capturing sites (hydroxyl and amine groups) with palladium. Also, the catalyst could be completely regenerated in a few cycles with simple centrifugation. This study will provide reliable foundation and extensive application way to further utilization of straw.

Cellulose-supported N-heterocyclic carbene-palladium catalyst: synthesis and its applications in the Suzuki cross-coupling reaction.

A cellulose-supported N-methylimidazole-palladium catalyst (Cell-NHC-Pd) was synthesized and used for Suzuki cross-coupling reactions between aryl halides and phenylboronic acids to create the corresponding coupling products in good to excellent yields. Moreover, the catalyst is easily recovered using only a few cycles of simple filtration.