Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 671
Filter
1.
Rev. bras. cir. cardiovasc ; 37(2): 200-206, Apr. 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1376527

ABSTRACT

Abstract Introduction: Drug-eluting stents (DES) coated with rapamycin or paclitaxel as antiproliferative substances significantly reduced the incidence of clinical restenosis and had fewer side effects after percutaneous coronary intervention. However, DES coated with rapamycin or paclitaxel still cause restenosis due to abnormal tissue growth which remained a therapeutic problem, particularly in certain subgroups, possibly due to drug concentrations. This study examined the impact of different concentrations of rapamycin and paclitaxel on cytokine, cell viability and proliferation in human aortic smooth muscle cells (HASMC)-derived foam cells. Methods: The foam cell model was established in vitro by incubating HASMC with 20 µg/mL oxidized low-density lipoprotein (ox-LDL) for 48 hours. Subsequently, foam cells were treated with different concentrations (0.01 µg/mL, 0.1 µg/mL, 0.5 µg/mL, 1 µg/mL, 5 µg/mL and 10 µg/mL) of rapamycin or paclitaxel for 48 hours, to measure cytokine, cell viability and proliferation by ELISA and MTT, respectively. Finally, viability and proliferation were measured by MTT after the foam cells were treated with 1 µg/mL rapamycin or paclitaxel combined with cytokine antibody for 48 hours. Results: After incubation of HASMC with ox-LDL, the ratios of cholesterol ester and total cholesterol increased significantly (55.29%) (P<0.01). Lipid staining with Oil Red O showed many lipid vacuoles and red dye particles in the cells. Meanwhile, cell viability and proliferation significantly increased compared with the control. This indicated that HASMC had been transformed into foam cells (P<0.01) while rapamycin or paclitaxel concentrations ≥0.1 µg/mL can significantly decrease the foam cell proliferation (P<0.05 or P<0.01), and 1 µg/mL of rapamycin or paclitaxel appeared the most effective concentration. As for cytokines, rapamycin or paclitaxel concentrations ≥1 ug/mL could significantly increase the level of inflammatory cytokines IL-6 (P<0.05 or P<0.01), which was enhanced with the increase of drug concentration. However, rapamycin or paclitaxel concentrations ≥1 µg/mL could significantly reduce the levels of anti-inflammatory cytokines IL-35 and transforming growth factor beta (TGF-β) (P<0.05 or P<0.01), which decreased with the increase of drug concentration. In addition, rapamycin or paclitaxel combined with anti-IL-1β, anti-IL-6, anti- TNF-α or anti-IL-35 had no significant effect on foam cell proliferation compared to the drug alone. However, rapamycin or paclitaxel combined with anti-IL-10 or anti-TGF-β can significantly enhance foam cell proliferation (P<0.01). In addition, there was no difference in the effects of the same concentrations of rapamycin and paclitaxel on foam cells. Conclusion: Although rapamycin or paclitaxel can reduce foam cell proliferation, too high or too low concentrations could decrease effectiveness. In particular, a high dose can induce foam cells to increase inflammatory cytokines secretion, reduce anti-inflammatory cytokines secretion, and thus affect the inhibiting proliferation. For rapamycin- and paclitaxel-eluting stents, this conclusion may explain the clinical observation of in-stent restenosis after percutaneous coronary intervention. DES coated with an appropriate concentration of rapamycin or paclitaxel may, at least to some extent, contribute significantly to reducing incidence of late in-stent restenosis.

2.
Rev. Assoc. Med. Bras. (1992) ; 68(2): 159-164, Feb. 2022. tab, graf
Article in English | LILACS | ID: biblio-1365364

ABSTRACT

SUMMARY OBJECTIVE: The objective of this study was to explore the molecular mechanism underlying the occurrence of benign bile duct stricture and the target of low-dose paclitaxel in the prevention of benign bile duct stricture. METHODS: Under the stimulation of transforming growth factor beta 1, the expression of collagen type I and connective tissue growth factor were detected on isolated primary fibroblasts. The phosphorylation levels of JNK and Smad2L were detected using Western blot. The effect of low-dose paclitaxel on the transforming growth factor beta 1-induced inhibition of type I collagen and connective tissue growth factor expression and JNK and Smad2L phosphorylation was also observed. RESULTS: Transforming growth factor beta 1 induced the secretion of type I collagen and connective tissue growth factor as well as JNK phosphorylation in biliary fibroblasts. The JNK inhibitor or siRNA-Smad2 inhibited the transforming growth factor beta 1-induced secretion of type I collagen and connective tissue growth factor. Low-dose paclitaxel inhibited the expression of type I collagen induced by transforming growth factor beta 1 and may inhibit the secretion of collagen in biliary fibroblasts. CONCLUSION: The activation of JNK/Smad2L induced by transforming growth factor beta 1 is involved in the occurrence of benign bile duct stricture that is mediated by the overexpression of type I collagen and connective tissue growth factor, and low-dose paclitaxel may inhibit the phosphorylation of JNK/Smad2L.


Subject(s)
Humans , Paclitaxel/pharmacology , Collagen , MAP Kinase Signaling System , Collagen Type I/metabolism , Collagen Type I/pharmacology , Smad2 Protein , Fibroblasts/metabolism
3.
Acta Pharmaceutica Sinica ; (12): 793-801, 2022.
Article in Chinese | WPRIM | ID: wpr-922901

ABSTRACT

Multicellular tumor spheroids (MCTS) can simulate the structure and metabolic characteristics of tumors in vivo, which is of great significance to study the metabolic phenotype of tumor cells and the mechanism of drug intervention. In this study, esophageal cancer MCTS were constructed, and MCTS frozen sections were prepared after treated with different formulations of paclitaxel (PTX) including common PTX injection, PTX liposome and albumin bound PTX. MCTS mass spectrometry imaging analysis method was established by using air flow assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI). The visualization of the permeation and enrichment process of PTX in MCTs after PTX treatment was realized, and the spatially resolved metabolomics of PTX injection group was studied. The results showed that the permeation and enrichment behavior of PTX in MCTs model were related to the formulations. The changes of endogenous metabolites in MCTs of esophageal cancer after treated with PTX injection had temporal and spatial characteristics. The metabolic changes of MCTS during the initial 0-4 hours were dominated by the down-regulation of middle-high polarity metabolites and some lipids in the central region of MCTS, while the metabolic changes of MCTS during 8-72 hours were mainly up-regulated by lipid metabolites in the peripheral region of MCTS. The combination of in vivo tumor-associated MCTs model with label free, highly sensitive and high coverage mass spectrometry imaging technology provided a new method and strategy for the study of pharmacometabolomics.

4.
China Pharmacy ; (12): 617-621, 2022.
Article in Chinese | WPRIM | ID: wpr-920734

ABSTRACT

OBJECTIVE To observe the clinical efficacy and safety of albumin-bound paclitaxel combined with nedaplatin inductive chemotherapy followed by concurrent radiochemotherapy in the treatment of loco-regionally advanced nasopharyngeal carcinoma. METHODS The clinical data of 45 patients (observation group ) with loco-regionally advanced nasopharyngeal carcinoma(Ⅲ/Ⅳa stage )who received albumin-bound paclitaxel combined with nedaplatin inductive chemotherapy in our hospital from August 2017 to July 2018 were retrospectively analyzed. Propensity score was used to match 45 patients(control group )with loco-regionally advanced nasopharyngeal carcinoma who received docetaxel combined with cisplatin and fluorouracil inductive chemotherapy. After inductive chemotherapy ,both groups received intensity-modulated radiochemotherapy (IMRT);observation group was additionally given concurrent nedaplatin chemotherapy ,and control groups was given concurrent cisplatin chemotherapy. Clinical efficacy and the incidence of ADR were compared between 2 groups. RESULTS All patients completed treatment and 3-year follow-up. After inductive chemotherapy and 1,3 months after concurrent radiochemotherapy ,there was no statistical significance in short-term response between 2 groups(P>0.05). There was no significantly difference in 3-years local control rate and 3-years free from distant metastasis between 2 groups(P>0.05). The incidences of leucopenia (grade 3 or above )in the observation group were significantly lower than those in the control group ,and the incidence of peripheral neuropathy in observation group was higher than that in control group (P<0.05). The incidences of thrombocytopenia (grade 2 or above ),rash and vomiting (grade 2 or above )in the observation group were lower than those in the control group ,but the difference was not statistically significant (P>0.05). There was no significant difference in the incidence of other ADR between 2 groups(P>0.05). CONCLUSIONS Albumin-bound paclitaxel combined with nedaplatin inductive chemotherapy followed by concurrent chemoradiotherapy in the treatment of loco-regionally advanced nasopharyngeal carcinoma is effective and tolerable .

5.
Acta Pharmaceutica Sinica ; (12): 233-241, 2022.
Article in Chinese | WPRIM | ID: wpr-913175

ABSTRACT

This paper aims to develop folic acid-modified paclitaxel nanocrystals (PTX NC@FA) with good stability, high drug loading and tumor cell targeting for endoscopic injection for preoperative local chemotherapy of gastric cancer. PTX NC@FA was prepared by the "bottom-up" followed by ultrasonic to study its morphology, particle size, ζ-potential, drug loading, folic acid-modified phospholipid (FA-DSPE-PEG2000) content, crystalline characteristics, stability, in vitro release, cytotoxicity against human gastric cancer cell line SGC-7901, and anti-tumor effect in two different tumor sizes (tumor volume 100 mm3 or 300 mm3) after single peri-tumor injection in a murine subcutaneous SGC-7901 tumor model. Animal experiments were approved by the Experimental Animal Ethics Committee of the School of Pharmacy, Fudan University. The resulting PTX NC@FA was of short rod-like shape, average particle size 175.3 ± 2.5 nm (PDI 0.17 ± 0.02), ζ- potential -2.5 ± 0.2 mV, PTX loading (28.23 ± 0.74) % (w/w) and FA-DSPE-PEG2000 content (4.40 ± 0.60) % (w/w). The size of the PTX NC@FA remained unchanged for 4 days in phosphate buffer with or without serum. Cellular growth inhibition effect on SGC-7901 showed the superiority of PTX NC@FA over nanocrystals without FA modification. PTX NC@FA inhibited tumor growth more efficiently than both nanocrystals without FA modification and commercially available paclitaxel injection (Taxol) 12 days after peri-tumor injection. For model tumor with the volume of 100 mm3, tumors of all animals in the PTX NC@FA group disappeared completely. For model tumor with the volume of 300 mm3, tumors of 3 animals in the PTX NC@FA group completely disappeared and tumors of the rest 4 animals also became significantly smaller with a tumor volume inhibition rate of 90%. PTX NC@FA showed good potential for preoperative chemotherapy of increase the chances of function preserving gastrectomy and improve the quality of life of patients.

6.
International Eye Science ; (12): 194-199, 2022.
Article in Chinese | WPRIM | ID: wpr-913021

ABSTRACT

@#AIM: To investigate the potential toxic effects of paclitaxel(PTX)on the proliferation, apoptosis, cell cycle, morphology, and blood-retinal barrier(BRB)of human retinal pigment epithelial cells(ARPE-19). <p>METHODS: ARPE-19 cells were cultured <i>in vitro</i> and divided into two groups: Control group(Control)and drug plus group(PTX). ARPE-19 cells were treated with different concentrations of PTX(0.005, 0.05, 0.5, 5mg/L)for a certain period of time(12, 24, 36, 48, 72h), and CCK8 assay and flow cytometry were used to detect the effects of drug on proliferation and apoptosis of ARPE-19 cells at different concentrations and time points. The same time, the cell cycle was detected by flow cytometry. Morphological changes of cells were observed by immunofluorescence. Expressions of apoptosis-related proteins and barrier function-related proteins were detected by Western blot. The effect of the drug on the cell barrier was measured by measuring the transepithelial resistance of the cells. <p>RESULTS: PTX reduced the proliferation ability of ARPE-19 cells. After 36h of treatment with low concentration of 0.005mg/L paclitaxel, cell proliferation began to be affected. At the same time, PTX accelerated cell apoptosis was dependent on drug concentration and time. Flow cytometry showed that the cells were arrested in the G2-M phase. In addition, PTX causes significant morphological changes in cells, with normal cells fusiform or irregular. In the PTX group, the number of cells decreased and the cell shape tended to be round. PTX affected retinal barrier function, and the transepithelial resistance of cells was significantly decreased after treatment, and the expression of tight junction proteins ZO-1 and Occludin were significantly decreased compared with the control group(<i>P</i><0.05). The expression levels of Cleaved-caspase-3 and Bax were significantly increased compared with the control group, while the expression levels of Bcl-2 were significantly decreased(<i>P</i><0.05)and was dependent on drug concentration and time. <p>CONCLUSION: PTX can affect the proliferation and apoptosis of ARPE-19 cells, and it depends on time and concentration. In addition, PTX affected the cell cycle and morphology of ARPE-19 cell. At the same time PTX can destroy the barrier function of the retina,suggesting that anti-tumor drugs have a potential toxic effect on the retina.

7.
Electron. j. biotechnol ; 50: 10-15, Mar. 2021. ilus, graf, tab
Article in English | LILACS | ID: biblio-1292308

ABSTRACT

BACKGROUND: LXYL-P1-2 is the first reported glycoside hydrolase that can catalyze the transformation of 7-b-xylosyl-10-deacetyltaxol (XDT) to 10-deacetyltaxol (DT) by removing the D-xylosyl group at the C7 position. Successful synthesis of paclitaxel by one-pot method combining the LXYL-P1-2 and 10- deacetylbaccatin III-10-b-O-acetyltransferase (DBAT) using XDT as a precursor, making LXYL-P1-2 a highly promising enzyme for the industrial production of paclitaxel. The aim of this study was to investigate the catalytic potential of LXYL-P1-2 stabilized on magnetic nanoparticles, the surface of which was modified by Ni2+-immobilized cross-linked Fe3O4@Histidine. RESULTS: The diameter of matrix was 20­40 nm. The Km value of the immobilized LXYL-P1-2 catalyzing XDT (0.145 mM) was lower than that of the free enzyme (0.452 mM), and the kcat/Km value of immobilized enzyme (12.952 mM s 1 ) was higher than the free form (8.622 mM s 1 ). The immobilized form maintained 50% of its original activity after 15 cycles of reuse. In addition, the stability of immobilized LXYL-P1-2, maintained 84.67% of its initial activity, improved in comparison with free form after 30 d storage at 4 C. CONCLUSIONS: This investigation not only provides an effective procedure for biocatalytic production of DT, but also gives an insight into the application of magnetic material immobilization technology.


Subject(s)
Paclitaxel/biosynthesis , Glycoside Hydrolases/metabolism , Kinetics , Enzymes, Immobilized , Nanoparticles , Magnets
8.
Acta Pharmaceutica Sinica B ; (6): 3272-3285, 2021.
Article in English | WPRIM | ID: wpr-922793

ABSTRACT

Co-delivery of chemotherapeutics and immunostimulant or chemoimmunotherapy is an emerging strategy in cancer therapy. The precise control of the targeting and release of agents is critical in this methodology. This article proposes the asynchronous release of the chemotherapeutic agents and immunostimulants to realize the synergistic effect between chemotherapy and immunotherapy. To obtain a proof-of-concept, a co-delivery system was prepared

9.
Acta Pharmaceutica Sinica B ; (6): 3244-3261, 2021.
Article in English | WPRIM | ID: wpr-922791

ABSTRACT

Major challenges for cancer treatment are how to effectively eliminate primary tumor and sufficiently induce immunogenic cell death (ICD) to provoke a robust immune response for metastasis control. Here, a self-assembled cascade bioreactor was developed to improve cancer treatment with enhanced tumor penetration and synergistic therapy of starvation, chemodynamic (CDT) and photothermal therapy. Ultrasmall FeS-GOx nanodots were synthesized with glucose oxidase (GOx) as template and induced by paclitaxel (PTX) to form self-assembling FeS-GOx@PTX (FGP)

10.
Acta Pharmaceutica Sinica B ; (6): 2048-2058, 2021.
Article in English | WPRIM | ID: wpr-888850

ABSTRACT

A commercial albumin-bound paclitaxel nano-formulation has been considered a gold standard against breast cancer. However, its application still restricted unfavorable pharmacokinetics and the immunogenicity of exogenous albumin carrier. Herein, we report an albumin-bound tumor redox-responsive paclitaxel prodrugs nano-delivery strategy. Using diverse linkages (thioether bond and disulfide bond), paclitaxel (PTX) was conjugated with an albumin-binding maleimide (MAL) functional group. These pure PTX prodrugs could self-assemble to form uniform and spherical nanoparticles (NPs) in aqueous solution without any excipients. By immediately binding to blood circulating albumin after intravenous administration, NPs are rapidly disintegrated into small prodrug/albumin nanoaggregates

11.
Article in Chinese | WPRIM | ID: wpr-908667

ABSTRACT

Objective:To explore the clinical effect of medroxyprogesterone acetate tablets combined with oxaliplatin and paclitaxel in the treatment of advanced endometrial cancer.Methods:Ninety-two patients with advanced endometrial cancer admitted to Qihe People′s Hospital of Shandong Province from January 2014 to May 2019 were selected. According to the entry number, they were divided into the observation group (the last number was odd, receiving medroxyprogesterone acetate tablets + oxaliplatin + paclitaxel treatment) and the control group (the last number was even, receiving oxaliplatin + paclitaxel treatment). The efficacy and safety of the two groups were evaluated, and the changes of serum human carbohydrate antigen 125 (CA125), vascular endothelial growth factor (VEGF), human epididymal protein (HE4) and immune function, physical status and quality of life before and after the treatment were compared and analyzed.Results:The total efficacy in the observation group was higher than that in the control group: 78.26%(36/46) vs. 58.70%(27/46), the difference was statistically significant ( P<0.05). After treatment, the levels of serum CA125, VEGF, HE4 in the observation group were lower than those in the control group: (23.27 ± 5.65) kU/L vs. (30.55 ± 5.71) kU/L, (214.94 ± 23.89) ng/L vs. (247.62 ± 19.97) ng/L, (26.62 ± 4.23) pmol/L vs. (32.24 ± 6.68) pmol/L, the differences were statistically significant ( P<0.05). After treatment, the levels of serum natural killer cells (NK), helper T lymphoid cells (Th), cytotoxic T lymphoid cells (Tc) in the observation group were higher than those in the control group: (0.287 ± 0.032 vs. 0.239 ± 0.027, 0.403 ± 0.052 vs. 0.333 ± 0.046, 0.261 ± 0.029 vs. 0.228 ± 0.026, the differences were statistically significant ( P<0.05). After treatment, the score of Eastern Cooperative Oncology Group (ECOG) in the observation group were lower than that in the control group: (1.37 ± 0.26) scores vs. (1.89 ± 0.34) scores; the score of Quality of Life Questionnaire(QLQ-C30) in the observation group was higher than that in the control group: (65.69 ± 7.58) scores vs. (58.35 ± 6.26) scores, the differences were statistically significant ( P<0.05). The incidence of adverse reactions between the two groups had no significant difference ( P>0.05). Conclusions:Medroxyprogesterone acetate tablets combined with oxaliplatin and paclitaxel is safe and effective in the treatment of advanced endometrial cancer. This method can reduce the concentration of tumor markers in patients, inhibit tumor angiogenesis, and improve immune function, physical fitness and quality of life.

12.
Article in Chinese | WPRIM | ID: wpr-907587

ABSTRACT

Objective:To compare the short-term clinical efficacy, adverse reactions and pharmacoeconomics of advanced mutation negative lung adenocarcinoma treated by albumin-bound paclitaxel or pemetrexed combined with cisplatin.Methods:From September 2019 to October 2020, 80 patients with advanced lung adenocarcinoma diagnosed in the First Affiliated Hospital of Bengbu Medical College were divided into observation group and the control group according to the randomized digital table, with 40 cases in each group. The observation group received albumin-bound paclitaxel combined with cisplatin, and the control group received pemetrexed combined with cisplatin. After 2 cycles of treatment, the short-term efficacy and the adverse reactions of the two groups were evaluated. The cost of chemotherapy drugs and the average length of hospital stay were compared between the two groups.Results:The objective response rates of the observation group and the control group were 30.0% (12/40) and 32.5% (13/40), the disease control rates were 77.5% (31/40) and 82.5% (33/40) respectively, and there were no significant differences ( χ2=0.058, P=0.809; χ2=0.313, P=0.576). The adverse reactions of the two groups were mainly grade Ⅰ-Ⅱ. The incidences of leucopenia, neutropenia, thrombocytopenia, hemoglobin decreased, gastrointestinal reaction, liver function damage and renal function damage in the observation group were 20.0% (8/40), 20.0% (8/40), 20.0% (8/40), 17.5% (7/40), 37.5% (15/40), 12.5% (5/40) and 7.5% (3/40) respectively, those in the control group were 25.0% (10/40), 20.0% (8/40), 17.5% (7/40), 15.0% (6/40), 32.5% (13/40), 17.5% (7/40) and 5.0% (2/40) respectively, and there were no statistically significant differences between the two groups ( χ2=0.287, P=0.592; χ2<0.001, P>0.999; χ2=0.082, P=0.775; χ2=0.092, P=0.762; χ2=0.220, P=0.639; χ2=0.392, P=0.531; χ2<0.001, P>0.999). The median cost of chemotherapy drugs and the median length of hospital stay in the observation group were 7 453 yuan and 6 days respectively, which were less than 8 956 yuan and 7 days in the control group, with statistically significant differences ( Z=-3.057, P=0.002; Z=-2.733, P=0.006). Conclusion:The short-term efficacy of albumin-bound paclitaxel combined with cisplatin is equal to pemetrexed combined with cisplatin in treatment of advanced mutation negative lung adenocarcinoma, and the adverse reactions are similar. However, the average cost of chemotherapy drugs of albumin-bound paclitaxel combined with cisplatin is less than pemetrexed combined with cisplatin, and the average length of hospital stay is shorter.

13.
Article in Chinese | WPRIM | ID: wpr-906189

ABSTRACT

Objective:To explore the potential targets and related mechanism involved in the paclitaxel resistance to ovarian cancer. Method:Ovarian cancer A2780 cells and A2780 paclitaxel-resistant cells (A2780/T) were treated by 2, 4, 8, 16, 32, 64, 128, 256 μmol·L<sup>-1</sup> paclitaxel (PTX) for 24 h or 48 h respectively <italic>in vitro</italic>. The proliferation rate of A2780 cells and A2780/T cells treated with paclitaxel was determined by methyl thiazolyl tetrazolium (MTT) colorimetric method assay. A2780 and A2780/T cells were analyzed by LC-MS/MS Label-Free quantitative proteomics to identify and screen differentially expressed proteins in the two groups of cells. Gene ontology (GO) annotation and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were used to determine the potential biomarkers of paclitaxel resistance in ovarian cancer. Conventionally cultured A2780 cells were used as a control group, and A2780/T cells were treated with 0, 1, 4 μmol·L<sup>-1</sup> PTX. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot methods were used to detect and verify the mRNA and protein expression levels of potential target transforming growth factor-<italic>β</italic>-activated kinase 1 binding protein 1 (TAB1) and its downstream related molecules transforming growth factor-<italic>β</italic>-activated kinase (TAK1) and p38. Result:After PTX treatment for 24 h and 48 h, the cell viability of A2780 and A2780/T cells decreased. The inhibitory rate of PTX on A2780 cells was significantly higher than that of A2780/T cells. In A2780 cells, the IC<sub>50</sub> of PTX treatment for 48 h was 0.002 μmol·L<sup>-1</sup>, while in A2780/T cells, the IC<sub>50 </sub>of PTX was greater than the maximum concentration of 128 μmol·L<sup>-1</sup>, indicating that A2780/T cells were resistant to PTX compared with A2780 cells. 441 differentially expressed proteins and 421 special differentially expressed proteins between A2780/T and A2780 cells were screened by label-free quantitative proteomic analysis. GO function enrichment analysis showed that the binding proteins accounted for the majority (80%) among the differentially expressed proteins. According to the results of KEGG pathway analysis and expression site analysis, TAB1 might be a potential biomarker in paclitaxel-resistant ovarian cancer. Compared with A2780 cells, mRNA and protein expression levels of TAB1 in A2780/T cells were significantly reduced (<italic>P</italic><0.01). mRNA expression of TAK1 and p38 that interacted with TAB1 were also significantly reduced (<italic>P</italic><0.05, <italic>P</italic><0.01), while there was no significant change in protein expression. Conclusion:TAB1 may be a potential biomarker of paclitaxel resistance to ovarian cancer , and its mechanism may be related to the TAB1/TAK1/p38 MAPK pathway.

14.
Acta Pharmaceutica Sinica B ; (6): 3935-3949, 2021.
Article in English | WPRIM | ID: wpr-922451

ABSTRACT

A significant proportion of non-small cell lung cancer (NSCLC) patients experience accumulating chemotherapy-related adverse events, motivating the design of chemosensitizating strategies. The main cytotoxic damage induced by chemotherapeutic agents is DNA double-strand breaks (DSB). It is thus conceivable that DNA-dependent protein kinase (DNA-PK) inhibitors which attenuate DNA repair would enhance the anti-tumor effect of chemotherapy. The present study aims to systematically evaluate the efficacy and safety of a novel DNA-PK inhibitor M3814 in synergy with chemotherapies on NSCLC. We identified increased expression of DNA-PK in human NSCLC tissues which was associated with poor prognosis. M3814 potentiated the anti-tumor effect of paclitaxel and etoposide in A549, H460 and H1703 NSCLC cell lines. In the four combinations based on two NSCLC xenograft models and two chemotherapy, we also observed tumor regression at tolerated doses

15.
Cancer Research and Clinic ; (6): 419-422, 2021.
Article in Chinese | WPRIM | ID: wpr-912899

ABSTRACT

Objective:To investigate the short-term efficacy and safety of albumin-bound paclitaxel combined with nedaplatin followed by concurrent radiotherapy in treatment of stage Ⅲ massive cervical cancer.Methods:The clinical data of 84 patients with massive cervical cancer admitted to Harbin Medical University Cancer Hospital from April 2019 to April 2020 were retrospectively analyzed. According to the different treatment regimens, patients were divided into the observation group and the control group, each with 42 cases. The observation group received albumin-bound paclitaxel combined with nedaplatin followed by concurrent radiotherapy, and the control group received solvent-based paclitaxel combined with nedaplatin followed by concurrent radiotherapy. The short-term efficacy and adverse reactions of the two groups were compared.Results:The partial remission (PR) rate of the observation group and the control group at 1 month of treatment was 92.9% (39/42) and 35.7% (15/42), respectively, and the difference was statistically significant ( χ2 = 29.867, P < 0.01). The complete remission (CR) rate of the observation group and the control group at 1 month after treatment was 59.5% (25/42) and 38.1% (16/42), respectively, and the difference was statistically significant ( χ2 = 3.859, P = 0.049). The incidence of diarrhea of the observation group was lower than that of the control group [33.33% (14/42) vs. 54.8% (23/42)], and the difference was statistically significant ( χ2 = 3.913, P = 0.048). There were no statistical differences in the incidence of hematological adverse reactions and abnormal liver and kidney functions between the two groups (all P > 0.05). Conclusion:The albumin-bound paclitaxel combined with nedaplatin followed by concurrent radiotherapy have a good short-term efficacy in treatment of stage Ⅲ massive cervical cancer, and the adverse reactions are tolerable.

16.
Article in Chinese | WPRIM | ID: wpr-861655

ABSTRACT

Objective: To investigate the efficacy and safety of paclitaxel combined with apatinib in comparison with paclitaxel alone as the second-line treatment for gastric cancer. Methods: Patients with advanced gastric cancer who had been treated at Chifeng Municipal Hospital, Chifeng Clinical Medical School of inner Mongolia Medical University, from March 2017 to March 2018 were enrolled. Inclusion criteria were human epidermal growth factor receptor-2(HER-2)-negative cancer and progression after the first-line treatment with fluorouracil combined with platinum. Patients were divided into groups administered with a single drug and combination of drugs. The single-drug group was administered with paclitaxel chemotherapy, while the combined-drug group with the paclitaxel combined with apatinib treatment. In both groups, the primary endpoint of observation was progression-free survival (PFS), while the secondary endpoint was the disease control rate (DCR), overall response rate (ORR), and safety. Results: A total of 60 patients were enrolled, including 30 patients in each of single- and combined-drug groups. PFS was significantly better in the combined-drug group than in the single-drug group (P0.05). The incidence of hypertension was significantly higher in the combined-drug group than in the single-drug group (P0.05). Conclusions: Paclitaxel combined with apatinib mesylate is superior to paclitaxel alone in the second-line treatment of gastric cancer. PFS, DCR, and ORR are superior with paclitaxel combined with apatinib mesylate than with paclitaxel alone. Although DCR and ORR in the combined-drug group were not significantly different from those in the single-drug group, the PFS was significantly longer in the combined-drug group, and the toxic and side effects of paclitaxel combined with apatinib mesylate were tolerable and safe.

17.
Article in Chinese | WPRIM | ID: wpr-883509

ABSTRACT

Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents.Administration of these drugs with siRNA is an efficacious strategy in this battle.Here,the present study tried to incor-porate siRNA and paclitaxel(PTX)simultaneously into a novel nanocarrier.The selectivity of carrier to target cancer tissues was optimized through conjugation of folic acid(FA)and glucose(Glu)onto its surface.The structure of nanocarrier was formed from ternary magnetic copolymers based on FeCo-polyethyleneimine(FeCo-PEI)nanoparticles and polylactic acid-polyethylene glycol(PLA-PEG)gene delivery system.Biocompatibility of FeCo-PEI-PLA-PEG-FA(NPsA),FeCo-PEI-PLA-PEG-Glu(NPsB)and FeCo-PEI-PLA-PEG-FA/Glu(NPsAB)nanoparticles and also influence of PTX-loaded nanoparticles on in vitro cytotoxicity were examined using MTT assay.Besides,siRNA-FAM internalization was investi-gated by fluorescence microscopy.The results showed the blank nanoparticles were significantly less cytotoxic at various concentrations.Meanwhile,siRNA-FAM/PTX encapsulated nanoparticles exhibited significant anticancer activity against MCF-7 and BT-474cell lines.NPsAB/siRNA/PTX nanoparticles showed greater effects on MCF-7 and BT-474 cells viability than NPsA/siRNA/PTX and NPsB/siRNA/PTX.Also,they induced significantly higher anticancer effects on cancer cells compared with NPsA/siRNA/PTX and NPsB/siRNA/PTX due to their multi-targeted properties using FA and Glu.We concluded that NPsAB nanoparticles have a great potential for co-delivery of both drugs and genes for use in gene therapy and chemotherapy.

18.
China Pharmacy ; (12): 1776-1779, 2021.
Article in Chinese | WPRIM | ID: wpr-882152

ABSTRACT

OBJECTIVE:To investigate the role of clinical pharmacists in the diagnosis and treatment of liposome-induced hand-food syndrome (HFS),and to provide reference for rational use of liposome preparation in clinic. METHODS :One case of elderly female patient with breast cancer ,admitted to our hospital suffered from HFS (grade 2)after treated with Doxorubicin hydrochloride liposome ;after successful therapy ,the patient had skin symptoms (grade 3)again due to Paclitaxel liposome ,and clinical pharmacist judged the recurrence of HFS. For symptomatic treatment ,stopping the treatment and external use of hormone was suggested ,and whole-process pharmaceutical care was provided. The pathogenesis ,differential diagnosis ,risk factors and therapeutic drugs of HFS were summarized based on literature review and 2 case reports in the database. RESULTS :The physicians adopted the suggestion of clinical pharmacists ;the patient ’s symptoms improved significantly on the third day and disappeared after 1 week. Combined with literature analysis and 2 case reports ,doxorubicin liposome metabolized more slowly than non liposomes in palms and soles of feet ,resulting in accumulation of doxorubicin in sweat duct and stratum corneum ,aggravating skin damage and leading to HFS. Sequential paclitaxel in liposome form may also lead to the accumulation in eccrine duct ,further caused skin damage and induced HFS. CONCLUSIONS :Clinical pharmacists actively participate in the diagnosis and treatment of ADR , which is conducive to the rehabilitation of patients. At same time ,combination or sequential of Paclitaxel liposome with PLD should be avoided ,as it can lead to ADR as HFS.

19.
China Pharmacy ; (12): 1611-1616, 2021.
Article in Chinese | WPRIM | ID: wpr-881464

ABSTRACT

OBJECTIVE:To evaluate th e effectiveness ,safety and economy of albu min-bound paclitaxel (nab-PTX)in the treatment of breast cancer by using rapid health technology assessment (HTA),and to provide evidence-based reference for drug selection. METHODS :Retrieved from PubMed ,the Cochrane Library ,CNKI,Wangfang database and other databases ,systematic evaluation/Meta-analysis,HTA and pharmacoeconomic studies about nab-PTX in the treatment of breast cancer were included ;the conclusions were classified and analyzed by using descriptive analysis. RESULTS :A total of 5 systematic reviews/Meta-analysis , 8 pharmacoeconomic studies were included in this study. Compared with conventional taxanes ,nab-PTX increased pathological complete response (pCR)rate [OR =1.39,95%CI(1.16,1.67),P<0.001] and event-free survival (EFS)[HR=0.69,95%CI(0.57, 0.85),P<0.001] in neoadjuvant chemotherapy (NAC)-treated breast cancer patients. However ,there were no significant differences in overall survival (OS),progression-free survival (PFS),objective response rate (ORR)and disease control rate (DCR)in metastatic breast cancer (MBC)patients between 2 groups. In the terms of safety ,nab-PTX increased the incidence of grade 3-4 sensory neuropathy [OR =1.89,95%CI(1.36,2.61),P<0.001] in MBC patients ,and increased the incidence of neutropenia [OR = 1.52,95%CI(1.23,1.88,P<0.001],sensory neuropathy [OR = 2.17,95%CI(1.38,3.40),P<0.001],rash [OR =1.46,95%CI mei1213@163.com (1.18,1.80),P<0.001] and fatigue [OR =1.28,95%CI(1.04, 1.56), P=0.02] in NAC -treated breast cancer patients.Pharmacoeconomic studies showed that nab-PTX could improve the quality adjusted lif e years of MBC patients compared with traditional taxanes ,and it was a economical option. CONCLUSIONS:Nab-PTX enhances pCR in NAC-treated breast cancer patients ,but has no significant advantage in the effectiveness of MBC patients ,and increases the occurrence of ADR. Nab-PTX may have a cost-utility advantage over conventional taxanes for MBC.

20.
Acta Pharmaceutica Sinica B ; (6): 55-70, 2021.
Article in English | WPRIM | ID: wpr-881124

ABSTRACT

Cancer stem cells (CSCs) are a subpopulation of cancer cells with functions similar to those of normal stem cells. Although few in number, they are capable of self-renewal, unlimited proliferation, and multi-directional differentiation potential. In addition, CSCs have the ability to escape immune surveillance. Thus, they play an important role in the occurrence and development of tumors, and they are closely related to tumor invasion, metastasis, drug resistance, and recurrence after treatment. Therefore, specific targeting of CSCs may improve the efficiency of cancer therapy. A series of corresponding promising therapeutic strategies based on CSC targeting, such as the targeting of CSC niche, CSC signaling pathways, and CSC mitochondria, are currently under development. Given the rapid progression in this field and nanotechnology, drug delivery systems (DDSs) for CSC targeting are increasingly being developed. In this review, we summarize the advances in CSC-targeted DDSs. Furthermore, we highlight the latest developmental trends through the main line of CSC occurrence and development process; some considerations about the rationale, advantages, and limitations of different DDSs for CSC-targeted therapies were discussed.

SELECTION OF CITATIONS
SEARCH DETAIL