Summary Background Previous studies have demonstrated the efficacy of apatinib and anlotinib for the treatment of sarcomas. However, more clinical data and evidence are needed to support clinical treatment selection and study design. Here, we evaluated the effectiveness and safety of these two drugs for the treatment of sarcomas. Methods We retrospectively reviewed the data of 110 patients with advanced osteosarcoma (n = 32) or soft tissue sarcoma (STS, n = 78) who received oral apatinib or anlotinib therapy during May 2016–February 2019 at two centers. Patients were divided into the apatinib and anlotinib groups. Results Among osteosarcoma patients, the objective response rates (ORRs) for the apatinib and anlotinib groups were 15.79% (3/19) and 7.69% (1/13), respectively. The disease control rates (DCRs) were 63.16% (12/19) and 30.77% (4/13), and the median progression-free survival (m-PFS) was 4.67 ± 3.01 and 2.67 ± 1.60 months, respectively. Among STS patients, ORRs for the apatinib and anlotinib groups were 12.24% (6/49) and 13.79% (4/29), respectively. The DCRs were 59.18% (29/49) and 55.17% (16/29), and m-PFS was 7.82 ± 6.90 and 6.03 ± 4.50 months, respectively. Regarding adverse events (AEs), apatinib was associated with a higher incidence of hair hypopigmentation and pneumothorax, while anlotinib was associated with a higher incidence of pharyngalgia or hoarseness. Conclusion Both apatinib and anlotinib were effective for the treatment of sarcomas. However, the effectiveness of the two drugs and associated AEs varied based on the histological type of sarcoma. These differences may be due to their different sensitivities to targets such as RET, warranting further study.

Metalloproteinase 9 (MMP-9) is able to degrade collagen IV, an important component of blood-brain barrier (BBB). Expression of MMPs, especially MMP-9, correlates with BBB disruption during central nervous system inflammation. Propofol has been reported to have anti-inflammation effects. In this study, we investigated the effects of propofol on TNF-α-induced MMP-9 expression in human cerebral microvascular endothelial cells (hCMEC/D3 cells) and explored the underlying mechanisms. The hCMEC/D3 cells were treated with propofol (25 μM), followed by TNF-α (25 ng/mL). We showed that TNF-α treatment markedly increased MMP-9 expression and decreased collagen IV expression in hCMEC/D3 cells, which was blocked by pretreatment with propofol. TNF-αinduced downregulation of collagen IV was also reversed by MMP-9 knockdown with siRNA. We revealed that TNF-α upregulated MMP-9 expression in hCMEC/D3 cells through activation of Ca 2+ /CAMK II/ERK/NF-κB signaling pathway; co-treatment with inhibitors of CaMK II (KN93), ERK (LY3214996), NF-κB (PDTC) or Ca 2+ chelator (BAPTA-AM) abrogated the effect of TNF-α on MMP-9 expression. We further established an in vitro BBB model by co-culturing of hCMEC/D3 cells and human astrocytes for 6 days and measuring trans-endothelial electrical resistance (TEER) to reflect the BBB permeability. TNF-α treatment markedly decreased TEER value, which was attenuated by pretreatment with propofol (25 μM) or MMP-9 knockdown with siRNA. In conclusion, propofol inhibits TNF-α-induced MMP-9 expression in hCMEC/D3 cells via repressing the Ca 2+ /CAMKII/ERK/NF-κB signaling pathway. TNF-αimpaired BBB integrity could be reversed by propofol, and propofol attenuates the inhibitory effect of TNF-α on collagen IV.

Lung cancer is the leading cause of cancer-related deaths worldwide, with 50-70% of patients suffering from bone metastasis. Accumulating evidence has demonstrated that miRNAs are involved in cell proliferation, migration, and invasion in malignancy, such as lung cancer bone metastasis. In the present study, we demonstrated that reduced miR-192-5p and increased TRIM44 levels were associated with the proliferation, migration and invasion of lung cancer. Furthermore, the potential functions of miR-192-5p were explored in A549 and NCI-H1299 cells. We found that miR-192-5p upregulation suppressed tumour behaviours in lung cancer cells. To further investigate whether miR-192-5p is associated with TRIM44, we used TargetScan software to predict the binding site between miR-192-5p and TRIM44. Luciferase activity assays were performed to verify this prediction. In addition, the significant role of miR-192-5p in negatively regulating TRIM44 expression was manifested by our research group. our results suggest that miR-192-5p inhibited the proliferation, migration and invasion of lung cancer through TRIM44.

Purpose: Anlotinib, a newly developed oral small-molecule receptor tyrosine kinase inhibitor (TKI), has been shown to have encouraging activity against sarcoma. The purpose of this study was to retrospectively evaluate the safety and clinical efficacy of chemotherapy combined with anlotinib plus anlotinib maintenance in advanced/metastatic soft tissue sarcoma (STS) patients in a real-world setting in China. Patients and Methods: We retrospectively collected the medical data of thirty-two patients with advanced/metastatic STS who received chemotherapy combined with anlotinib plus anlotinib maintenance therapy. The objective response rate (ORR) and disease control rate (DCR) were calculated according to the RECIST 1.1 criteria. The progression-free rates (PFRs) at three and six months, the progression-free survival (PFS) time, and adverse events were recorded. Results: On the basis of investigator assessments, two patients (6%) achieved CR (complete response) and nine patients (28%) achieved PR (partial response), with an ORR of 34%. Eleven patients (34%) achieved SD (stable disease), and ten patients (31%) achieved PD (progression disease), with a DCR of 69%. The progression-free rates (PFRs) at three and six months were 81% and 69%, respectively. The median PFS time was 8.2 months. The hematologic and non-hematologic toxicities were manageable. The most common grade 3 and 4 adverse events were febrile neutropenia (9%), leukopenia (19%), thrombocytopenia (3%), anemia (6%), anorexia (6%), vomiting (3%), and hypertension (6%). The combination therapy was generally well tolerated. Conclusion: Our study suggests that chemotherapy combined with anlotinib plus anlotinib maintenance therapy had good efficacy and resulted in more favorable survival with good tolerance among patients with advanced/metastatic STS.

Rate constants for the reactions of and with the esters methyl formate, ethyl formate, methyl NO 3 ~, SO 4 ~~Clã cetate and ethyl acetate in aqueous solution have been measured using pulse radiolysis and laser Ñash photolysis. The reactivities of and are compared with and found to be roughly in the NO 3 ~, SO 4 ~~Cl~~OH order The rates of reaction of with the formate esters in the aqueous phase Cl~B ~OH A NO 3 ~B SO 4 ~~. N O 3 ãre about four orders of magnitude faster than their corresponding gas phase reactions. In contrast, the rate constants for reaction of with formate and acetate esters in the aqueous phase are about 100 times smaller Clt han the gas phase values.

Allylic oxidation of cychohexene under atmospheric pressure of molecular oxygen was carried out over cobalt resinate in the absence of solvent. It was shown that cobalt resinate exhibited promising catalytic activity for the oxidation of cyclohexene to 2-cyclohexen-1-ol and 2-cychohexen-1-one under mild condition for the first time.

Recently, apatinib has been shown to be effective in treating sarcoma. This study aimed to assess the safety and efficacy of apatinib in the treatment of patients with osteosarcoma after failed of standard multimodal therapy and to compare the therapeutic effects of apatinib on osteosarcoma between high-dose group and low-dose group. A total of 27 patients with osteosarcoma who received apatinib between January 2016 and August 2017 were retrospectively reviewed. Among the 27 patients, the objective response rate (ORR) and the disease control rate (DCR) were 25.93% and 66.67%, respectively. The median of progression-free survival (m-PFS) was 3.5 months (95% confidence interval [CI], 2.5–4.8 months), and the median of overall survival (m-OS) was 9.5 months (95% CI, 7.8–10.5 months). There was no statistically significant difference in ORR (36.36% vs 18.75%), DCR (63.64% vs 68.75%), m-PFS (4.3 months [95% CI, 1.8–7 months) vs 3.35 months (95% CI, 1.8–4 months]), and m-OS (9.5 months [95% CI, 7.8–10.5 months] vs 9.4 months [95% CI, 7.8–10.8 months]) ( P > .05) between the high-dose group (the average dose was 659 mg/qd) and the low-dose group (the average dose was 516 mg/qd). Most of the adverse events (AEs) were in grade 1 or grade 2. The main AEs in grade 3 were hypertension, rash, weight loss, hand-foot syndrome, and diarrhea. Apatinib is safe and effective in the treatment of advanced osteosarcoma. We recommend that the initial dose of apatinib should be 500 mg/qd in the treatment of osteosarcoma.

BackgroundWhile performing sacrectomy from a posterior approach enables the en bloc resection of sacral tumors, it can result in deep posterior peritoneal defects and postoperative complications. We investigated whether defect reconstruction with gluteus maximus (GLM) adipomuscular sliding flaps would improve patient outcomes.MethodsBetween February 2007 and February 2012, 48 sacrectomies were performed at He Nan Cancer Hospital, Zhengzhou City, China. We retrospectively examined the medical records of each patient to obtain the following information: demographic characteristics, tumor location and pathology, oncological resection, postoperative drainage and complications. Based on the date of the operation, patients were assigned to two groups on the basis of closure type: simple midline closure (group 1) or GLM adipomuscular sliding reconstruction (group 2).ResultsWe assessed 21 patients in group 1 and 27 in group 2. They did not differ with regards to gender, age, tumor location, pathology or size, or fixation methods. The mean time to last drainage was significantly longer in group 1 compared to group 2 (28.41 days (range 17–43 days) vs. 16.82 days (range 13–21 days, P < 0.05)) and the mean amount of fluid drained was higher (2,370 mL (range 2,000–4,000 mL) vs. 1,733 mL (range 1,500–2,800 mL)). The overall wound infection rate (eight (38.10%) vs. four (14.81%), P < 0.05) and dehiscence rate (four (19.05%)] vs. three (11.11%), P < 0.05) were significantly higher in group 1 than in group 2. The rate of wound margin necrosis was lower in group 1 than in group 2 (two (9.82%) vs. three (11.11%), P < 0.05).ConclusionsThe use of GLM adipomuscular sliding flaps for reconstruction after posterior sacrectomy can significantly reduce the risk of infection and improve outcomes.