Multidrug resistance (MDR) remains the major obstacle to the success of clinical cancer chemotherapy. P-glycoprotein (P-gp), encoded by the MDR1, is an important part with complex mechanisms associated with the MDR. In order to overcome the MDR of tumors, we in the present experimental design incorporated small interfering RNA (siRNA) targeting MDR1 gene and anticancer drug paclitaxel (PTX) into the solid lipid nanoparticles (SLNs) to achieve the combinational therapeutic effects of genetherapy and chemotherapy. In this study, siRNA-PTX-SLNs were successfully prepared. The cytotoxicity of blank SLNs and siRNA-PTX-SLNs in MCF-7 cells and MCF-7/ADR cells were detected by MTT; and the uptake efficiency of PTX in MCF-7/ADR cells were detected via HPLC method; quantitative real-time PCR and flow cytometry were performed to investigate the silencing effect of siRNA-PTX-SLNs on MDR1 gene in MCF-7/ADR cells. The results showed that PTX loaded SLNs could significantly inhibit the growth of tumor cells, and more importantly, the MDR tumor cells treated with siRNA-PTX-SLNs showed the lowest viability. HPLC study showed that SLNs could enhance the cellular uptake for PTX. Meanwhile, siRNA delivered by SLNs significantly decreased the P-gp expression in MDR tumor cells, thus increased the cellular accumulation of rhodamine123 as a P-gp substrate. In conclusion, the MDR1 gene could be silenced by siRNA-PTX-SLNs, which could promote the growth inhibition efficiency of PTX on tumor cells, leading to synergetic effect on MDR tumor therapy.
Objective To compare the distribution of drug concentration in lymph nodes and blood between lymphatic chemotherapy and single drug chemotherapy and to study if nano carbon can enhance the number of lymph node dissection. Methods From June 2015 to February 2016, 80 patients with esophageal cancer in the Department of Thoracic Surgery, West China Hospital were enrolled and they were divided into two groups: a lymphatic chemotherapy with paclitaxel (LCP) group and a paclitaxel alone (PTX) group. There were 35 males and 5 females with an average age of 60.63±8.78 years in the LCP group, and 30 males and 10 females with an average age of 62.13±7.89 years in the the PTX group. We observed the incidence rate of complications after operation, the number of lymph node dissection and the rate of lymph node metastasis. The drug concentration in the blood and lymph nodes between the two groups was compared. Results The postoperative morbidity did not increase in the both groups, which did not have adverse drug reactions such as bone marrow suppression, gastrointestinal reaction and so on. The concentration of chemotherapy drug in lymph nodes in the LCP group was higher than that in the PTX group. The LCP group collected 771 lymph nodes, and the average number was 19.27±7.77 for each patient; the PTX group collected 658 lymph nodes, and the average number was 16.45±7.12 for each patient; but the difference between two groups was not statistically significant (P>0.05). Conclusion Nano carbon carriers can effectively improve the drug concentration in lymph nodes after the local injection of chemotherapy drugs. The use of nano carbon tracer in the operation to improve lymph node dissection may not have significance.
Partial least square (PLS) combining with Raman spectroscopy was applied to develop predictive models for plasma paclitaxel concentration detection. In this experiment, 312 samples were scanned by Raman spectroscopy. High performance liquid chromatography (HPLC) was applied to determine the paclitaxel concentration in 312 rat plasma samples. Monte Carlo partial least square (MCPLS) method was successfully performed to identify the outliers and the numbers of calibration set. Based on the values of degree of approach (Da), moving window partial least square (MWPLS) was used to choose the suitable preprocessing method, optimum wavelength variables and the number of latent variables. The correlation coefficients between reference values and predictive values in both calibration set (Rc2) and validation set (Rp2) of optimum PLS model were 0.933 1 and 0.926 4, respectively. Furthermore, an independent verification test was performed on the prediction model. The results showed that the correlation error of the 20 validation samples was 9.36%±2.03%, which confirmed the well predictive ability of established PLS quantitative analysis model.
ObjectivesTo evaluate the economic efficacy of nab-paclitaxel (NAB-P) combined with gemcitabine (GEM) versus GEM alone in the treatment of metastatic pancreatic cancer in China.MethodsA Markov model simulating the costs and health outcomes was developed to estimate quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER). The impact of parameter uncertainty on the model was assessed by deterministic one-way sensitivity analysis.ResultsNAB-P combined with GEM was shown superior efficacy compared to gemcitabine monotherapy, however with higher costs. The ICER between the two groups was 964 780.79￥/QALY.ConclusionsCompared with gemcitabine monotherapy, NAB-P combined with GEM is not cost-effective. The conclusion is confirmed by deterministic one-way sensitivity analysis.
ObjectiveTo systematically evaluate the clinical efficacy and adverse reactions of paclitaxel and carboplatin with or without bevacizumab in the treatment of non-small cell lung cancer (NSCLC).MethodsThe databases including PubMed, The Cochrane Library, EMbase, CNKI, Wanfang Data, VIP and CBM were searched from inception to October 2022 to collect randomized controlled trials of the clinical efficacy of paclitaxel and carboplatin with or without bevacizumab for the treatment of NSCLC. RevMan 5.4 software was used for meta-analysis.ResultsEight randomized controlled trials were enrolled, involving a total of 1 724 patients. Meta-analysis showed that for the treatment of NSCLC, the disease control rate, overall response rate, 1-year survival rate, and 2-year survival rate were higher in the trial group (paclitaxel and carboplatin combined with bevacizumab) than those in the control group (paclitaxel and carboplatin) (P<0.05); however, the incidences of the adverse reactions, such as leukopenia, hemorrhage, proteinuria and hypertension, etc, were higher in the trial group than those in the control group (P<0.05). There were no statistical differences between the trial group and the control group in the incidences of fatigue, thrombocytopenia, neutropenia or hyponatremia, etc (P>0.05). In addition, the median progression-free survival and overall survival were longer in the trial group than those in the control group.ConclusionFor the treatment of NSCLC, paclitaxel and carboplatin combined with bevacizumab is superior in terms of disease control, overall response and prolonging patient survival, etc, but will be associated with more adverse reactions.