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Background To explore the pharmacodynamic evaluation and mechanism research of BOC26P against breastcancer, and to provide a basis for the treatment of breast cancer.Method MTT assay was used to detect the cytotoxicity of BOC26P against 4 breast cancer cell lines (MCF7/TAX, MDA-MB-231/PT, MDA-MB-231and MCF-7), and as well as the non-tumor cell lines MCF-10A, in variousdrug concentrations (from 0.004 to 1 μM). Western Blotting and Real-Time PCR assay were used to detect therelative protein and gene expression level after treatment with BOC26P in MCF-7/TAX. The effect of BOC26Pon Specific fluorescent P-gp substrate accumulation in MCF-7/TAX was analyzed by flow cytometry; Moleculardocking was used to analyze the binding capacity between BOC26P, Cyclosporine A, and Verapamil. FCM assaystaining with Annexin V-FITC/PI and Propidium iodide was used to measure the apoptosis and the cell cycleafter treatment with BOC26P in MCF-7/TAX, MDA-MB-231/PT, MDA-MB-231, and MCF-7; Detection ofmitochondrial membrane potential after treatment with BOC26P inMCF-7/TAX, MDA-MB-231/PT, MDA-MB231and MCF-7; Western Blotting and Real-Time PCR assay was used to detect the apoptosis relative proteinand gene expression level after treatment with BOC26P in MDA-MB-231, MCF-7, MDA-MB-231/PT, and MCF7/ADR.Results Cytotoxicity assay showed that BOC26P could effectively suppress 4 breast cancer cell lines (MCF7/TAX, MDA-MB-231/PT, MDA-MB-231, and MCF-7) with an IC50 value of under 0.5 μM. The IC50 value ofBOC26P on non-tumor cells MCF-10A was 32.29 μM. The binding ability of BOC26P to P-gp in breast cancercells was weak. There was no significant effect on the intracellular accumulation of Rhodamin 123(Rh123), Pgp binding specific fluorescence substrate, and multi-drug resistance protein P-gp expression in MCF-7/ADRand MDA-MB-231/PT tumor cells; BOC26P induced MCF-7/TAX, MDA-MB-231/PT, MDA-MB-231 and MCF-7cells cycle arrest at G2/M phase and lead to cell apoptosis. BOC26P induced significant activation of p53protein in MCF-7/ADR and MAD-MB-231/TAX cells. Under the same conditions, BOC26P promoted Baxexpression while inhibited Bcl-2 expression, and could significantly cause activation of Cleveland PARP andClevead Caspase3. The results demonstrated that BOC26P may induce apoptosis through the death receptorapoptosis pathway.Conclusion It is known that BOC26P has a significant proliferation inhibitory effect on breast cancer cellswithout serious side effects. BOC26P has the Potential to be developed into a clinical substitute drug for triple-
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Objective BOC26P is a potent anticancer candidate which inhibits microtubule polymerization and shows strongcytotoxic activity against numerous cancer cell lines and drug resistant cell lines. To support the pharmacokineticstudy of BOC26P, a rapid, selective and reproducible UPLC-MS/MS method was developed.Method Dexamethasone sodium phosphate (DSP) was used as an internal standard (IS). Following proteinprecipitation by using methanol-acetonitrile solution (1:1, v/v) with an internal standard DSP, the processedsamples were chromatographed on an UPLC X Bridge 71 TM C8 column (4.6 mm × 100 mm, 3.5 μm) with a mobilephase that consisted of acetonitrile and 2mmol/L ammonium acetate aqueous solution (containing 0.25%ammonia) with a gradient elution pumped at a flow rate of 0.4 mL/min. Mass spectrometric detection wasperformed in the positive electrospray ionization mode by multiple reaction monitoring (m/z 428.84→198.92 and472.90→434.93 for BOC26P and DSP, respectively). The quantification of BOC26P in rat plasma was fully verified.Results The linearity was established in the range of 50 to 2000 ng/mL(r2≥0.99). The recovery of BOC26P fromspiked plasma were ranged from 96.7% to 110.5%. This method showed acceptable accuracy (3.7% to 6.3%) andprecision (1.5% to 3.1%) both of intra- and inter-day.Conclusion The developed method was successfully applied for three intravenous dose (2, 5, 12.5 mg/kg BOC26P)pharmacokinetics in male and female rats
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@#Objective To explore the practical feasibility of the weaving technique for pectus carinatum. Methods From January 2011 to December 2018, a total of 51 patients with pectus carinatum, including 47 males and 4 females at age of 9-29 (13.7±2.9) years, were applied with minimally invasive waving technique for the correction. The steel plate was inserted through the subcutaneous layer, intercostal space and over the sternal surface under direct thoracoscopic vision. The number of implanted steel plates was determined by the degree of chest wall deformity. The steel plate was removed 2 years after surgery. Results All the operations were successfully completed, the average operation time was 63.9±15.8 min, the amount of bleeding was 19.8±8.8 mL, and the duration of postoperative hospitalization was 4.6±1.6 d. The adverse events included intercostal artery injury (n=2), pneumothorax (n=4), pleural effusion (n=3) and skin rupture (n=1). And there were 29 patients of moderate pain (numerical rating scale 4-6 points) on the first day after surgery, but no patient was asked to remove the steel palate due to intolerable discomfort. All patients were followed up after plate placement. Of the 51 patients, the plates were removed in 37 patients until 2 years after placement, and the duration of postoperative hospitalization was 1.4±0.5 d. After 33 (1-48) months of routine follow-up after the removal of the plate, 22 patients achieved excellent outcomes and 9 patients with good outcomes. Besides, there were 5 patients with fair outcome and 1 patient with poor outcome. No adverse effect was found in growth and development after the steel plate placement. Conclusion Minimally invasive weaving technique is a safe, feasible, effective and individualized operation for pectus carinatum with substantial thoracic reconstruction.