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BMC Cancer ; 21(1): 1278, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34836510


BACKGROUND: Whereas there are many pharmacological interventions prescribed for patients with advanced anaplastic lymphoma kinase (ALK)- rearranged non-small cell lung cancer (NSCLC), comparative data between novel generation ALK-tyrosine kinase inhibitors (TKIs) remain scant. Here, we indirectly compared the efficacy and safety of first-line systemic therapeutic options used for the treatment of ALK-rearranged NSCLC. METHODS: We included all phase 2 and 3 randomised controlled trials (RCTs) comparing any two or three treatment options. Eligible studies reported at least one of the following outcomes: progression free survival (PFS), overall survival (OS), objective response rate (ORR), or adverse events of grade 3 or higher (Grade ≥ 3 AEs). Subgroup analysis was conducted according to central nervous system (CNS) metastases. RESULTS: A total of 9 RCTs consisting of 2484 patients with 8 treatment options were included in the systematic review. Our analysis showed that alectinib (300 mg and 600 mg), brigatinib, lorlatinib and ensartinib yielded the most favorable PFS. Whereas there was no significant OS or ORR difference among the ALK-TKIs. According to Bayesian ranking profiles, lorlatinib, alectinib 600 mg and alectinib 300 mg had the best PFS (63.7%), OS (35.9%) and ORR (37%), respectively. On the other hand, ceritinib showed the highest rate of severe adverse events (60%). CONCLUSION: Our analysis indicated that alectinib and lorlatinib might be associated with the best therapeutic efficacy in first-line treatment for major population of advanced NSCLC patients with ALK-rearrangement. However, since there is little comparative evidence on the treatment options, there is need for relative trials to fully determine the best treatment options as well as the rapidly evolving treatment landscape.

Artigo em Inglês | MEDLINE | ID: mdl-34646330


Patients with EGFR gene mutation often obtain de novo resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) or develop secondary resistance to EGFR-TKIs after taking EGFR-TKI therapy. Traditional Chinese medicine (TCM) with different treatment principles, in combination with EGFR-TKIs, plays an important role in the treatment of cancers including resistant non-small cell lung cancer (NSCLC). However, inappropriate use of TCM herbs may induce resistance to gefitinib. Therefore, it is of a great value to evaluate which TCM treatment principle should be combined with EGFR-TKIs, and which one should be avoided, and find out the potential mechanisms. The lentiviral transfection assay was used for overexpression of PIK3CA mutation gene in PC-9 cells to construct PC-9-PIK3CA-mutation (PC-9-PIK3CA-M) cells. Cell proliferation, apoptosis, and the expression of EGFR/PI3K/AKT and EGFR/RAS/RAF/ERK in PC-9-PIK3CA-M and H1975 cells treated by the typical cooling-heat drug, Qing-kai-ling (QKL) and Tan-re-qing (TRQ), or the typical warming-yang drug, Shen-fu (SF) and gefitinib treatment, were detected by MTT, Annexin V/PI double labeling, and Western blot assays, respectively. Tumor xenograft and immunohistochemistry experiments were carried out to confirm the in vitro findings. PC-9-PIK3CA-M cells were less sensitive to gefitinib, when compared with PC-9 cells. QKL injection and TRQ injection, not SF injection, combined with gefitinib induced significantly increased cell growth inhibition and apoptosis in PC-9-PIK3CA-M and H1975 cells. SF injection antagonized the effect of gefitinib in promoting cancer cell apoptosis. QKL injection and TRQ injection increased the sensitivity of gefitinib by inhibiting the phosphorylation of AKT or ERK in H1975 and PC-9-PIK3CA-M cells. Similar findings were observed in vivo in H1975 xenograft mouse model. QKL and TRQ, with cooling-heat TCM treatment principle, should be combined with gefitinib in the treatment of NSCLC. Furthermore, warming-yang drug SF should be avoided to be used together with EGFR-TKIs.

Protein Expr Purif ; 128: 86-92, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27546453


Recombinant protein purification remains to be a major challenge in biotechnology and medicine. In this paper we report a simple method for recombinant protein purification using self-assembling peptide-tagged tobacco etch virus protease (TEVp). After construction of an N-terminal ELK16 peptide fusion expression vector, we expressed ELK16-TEVp fusion protein in E. coli. SDS-PAGE analysis showed that ELK16-TEVp was expressed as active protein aggregates which could be purified to 91% purity with 92% recovery by centrifugation in the presence 0.5% Triton X-100. By using His-tagged bovine interferon-γ (His-BoIFN-γ) as the substrate, we demonstrated that EKL16-TEVp had a protease activity of 1.3 × 10(4) units/mg protein with almost 100% cleavage efficiency under the optimized conditions. More importantly, EKL16-TEVp could be removed from the cleavage reaction by single-step centrifugation. After removing the His-tag by nickel-conjugated agarose bead absorption, the recombinant BoIFN-γ (rBoIFN-γ) was purified to 98.3% purity with 63% recovery. The rBoIFN-γ had an antiviral activity of 1.6 × 10(3) units/mg protein against vesicular stomatitis virus. These data suggest that ELK16-TEVp may become a universal tool for recombinant protein purification.

Endopeptidases , Interferon gama/química , Vírus de Plantas/genética , Proteólise , Animais , Bovinos , Endopeptidases/biossíntese , Endopeptidases/química , Endopeptidases/genética , Endopeptidases/isolamento & purificação , Escherichia coli/genética , Escherichia coli/metabolismo , Vírus de Plantas/enzimologia , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/isolamento & purificação
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(5): 1615-22, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-30001072


Hyperspectral remote sensing data have special advantages, i.e., they have high spectral resolution and strong band continuity, and a great number of spectral information could be widely used in soil properties monitoring research. Using hyperspectral remote sensing technique to analyze saline soil properties makes great significance for the crop growth in the irrigation district and agricultural sustainable development. 221 soil samples were collected from Manasi River Basin to measure soil electrical conductivity (EC), soil organic matter (SOM) and 3 kinds of cation concentrations including Na+, Ca2+ and Mg2+, which were used to obtain sodium adsorption ration value (SAR). The soil hyperspectral curves were also measured. EC, SOM and SAR models were established based on the six spectral-related indices, including raw reflectance (R), standard normal variable (SNV), normalized difference vegetation index (NDVI), logarithm of the reciprocal (LR), the first derivative reflectance (FDR) and continuum-removal reflectance (CR) by the stepwise linear regression method. The results showed that, compared to the other five models, the model of log (EC)~R had the highest accuracy with r value of 0.782 and RMSE value of 0.256. The model of SOM vs. NDVI had the highest accuracy with r value of 0.670 and RMSE value of 5.352. The model of SAR vs. FDR had the highest accuracy with r value of 0.647 and RMSE value of 1.932. As to the model accuracy of the studied soil physico-chemical properties, the log(Ec) model was the most effective one, followed by the SOM model, the SAR model was the most inaccurate. The sensitive wavelengths for EC, SOM and SAR distributed in 395~1 801 nm, 352~1 144 nm and 394~1 011 nm, respectively. Since soil physico-chemical properties were highly spatially variable, there were large differences for the model establishment and validation of the soil properties. This research could be a reference of hyperspectral remote sensing monitoring of salinized soils.

Ying Yong Sheng Tai Xue Bao ; 27(12): 3769-3776, 2016 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-29704333


Soil water repellency (SWR) impedes the processes of soil water infiltration and redistribution. Although water repellent soils exist extensively in the world, its causes were not very clear. In this research, three measurement methods including the water droplet penetration time (WDPT), the molarity of ethanol drop (MED) and the contact angle (denoted as θ below) methods, were applied to obtain different SWR indices for the tested soils collected in Manas River Basin, Xinjiang Uygur Autonomous Region, China. The height method and the mass method were conducted to measure θ values. WDPT values of different soil samples were compared to investigate whether WDPT values were affected after being oven-dried or by different bulk densities. The relationships among three SWR indices (WDPT, MED and θ) were compared, and the major soil physico-chemical properties which influenced SWR were analyzed to discuss the intrinsic mechanism that caused SWR. The results showed that WDPT values of higher bulk density were larger than those of lower bulk density, and WDPT values of oven-dried soils were larger than those of air-dried soils. There were correlations between the three SWR indices of WDPT, MED and θ, but MED was insignificantly related to θ, which showed the differences among various SWR indices, although they were related to each other. When measuring θ values of soil-water, θ values obtained using the height method were larger than those obtained using the mass method, and the differences of θ for the three replications with the height method were smaller than those with the mass method. When using octane as the reference liquid for measuring θ values of soil-water, the differences of the three replications were small, being lower than those using ethyl alcohol. Among the studied multi-physico-chemical properties, clay content affected WDPT and θ values more significantly than other soil physico-chemical properties. Concentrations of K+ and Na+ were both positively correlated to θ va-lues, while the content of montmorillonite was negatively correlated to WDPT and MED values. In summary, among the three SWR measurement methods, the WDPT method was quite simple in operation but was susceptible, the MED method shortened the infiltration time but was time-consuming in operation, and the contact angle method was complicated in operation but the results were relatively accurate. When using octane as the reference liquid for the height method, it was more reliable than using the other liquids. Because each index had its inherent nature, it was suggested to use multiple indices to characterize SWR comprehensively.

Solo , Água , China , Rios