Objectives:Acquired resistance to paclitaxel represents a critical barrier to the effective chemotherapy of non-small cell lung cancer(NSCLC).The present study aimed to elucidate the molecular and pharmacological mech...Objectives:Acquired resistance to paclitaxel represents a critical barrier to the effective chemotherapy of non-small cell lung cancer(NSCLC).The present study aimed to elucidate the molecular and pharmacological mechanisms promoting paclitaxel resistance in NSCLC and to explore potential strategies for overcoming this resistance.Methods:Here,we report an integrated pharmacological and analytical approach to quantify paclitaxel disposition and overcome resistance in a A549/TAX cell model(paclitaxel-resistant A549 cells).Results:Cell counting kit-8(CCK-8)assay,colony formation,and apoptosis assays confirmed that A549/TAX cells exhibited marked resistance to paclitaxel relative to parental A549 cells.Based on transcriptome profiling by RNA sequencing analysis and validation by western blotting assay,we found that the expression of the ATP-binding cassette subfamily B member 1(ABCB1)(the encoded protein is termed P-glycoprotein)was significantly upregulated in resistant cells.By using ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),we demonstrated that ABCB1 overexpression promotes enhanced efflux of intracellular paclitaxel,thereby lowering its cytotoxic accumulation.Genetic silencing of ABCB1 or pharmacological inhibition with the specific P-glycoprotein modulator elacridar or tariquidar restored intracellular paclitaxel levels,as determined by UPLC-MS/MS,and synergistically decreased cell viability as observed in CCK-8 assay.Conclusion:These findings reveal that the ABCB1-mediated drug efflux is a crucial mechanism underlying paclitaxel resistance in NSCLC cells,with UPLC-MS/MS serving as a sensitive analytical method to detect paclitaxel concentration.Inhibition of ABCB1 is a promising therapeutic strategy to resensitize resistant tumor cells to paclitaxel.展开更多
Paclitaxel(PTX),a valuable natural product derived from Taxus species,exhibits remarkable anti-cancer properties.It penetrates nanopores in microtubule walls,interacting with tubulin on the lumen surface and disruptin...Paclitaxel(PTX),a valuable natural product derived from Taxus species,exhibits remarkable anti-cancer properties.It penetrates nanopores in microtubule walls,interacting with tubulin on the lumen surface and disrupting microtubule dynamics,thereby inducing cytotoxic effects in cancer cells.PTX and its derivatives have gained approval for treating various diseases due to their low toxicity,high efficiency,and broad-spectrum application.The widespread success and expanding applications of PTX have led to increased demand,raising concerns about accessibility.Consequently,researchers globally have focused on developing alternative production methods and applying nanocarriers in PTX delivery systems to enhance bioavailability.This review examines the challenges and advancements in PTX sourcing,production,physicochemical properties,anti-cancer mechanisms,clinical applications,trials,and chemo-immunotherapy.It aims to provide a comprehensive reference for the rational development and effective utilization of PTX.展开更多
Objective Chemoresistance,such as paclitaxel(PTX)resistance,has become a great obstacle in non-small cell lung cancer(NSCLC)treatment.The natural agent salidroside(SAL)has been shown to exert an antitumor effect on NS...Objective Chemoresistance,such as paclitaxel(PTX)resistance,has become a great obstacle in non-small cell lung cancer(NSCLC)treatment.The natural agent salidroside(SAL)has been shown to exert an antitumor effect on NSCLC.Nonethe-less,it is unclear whether SAL can decrease the resistance of NSCLC to PTX.Methods PTX-resistant NSCLC cells(H1299/PTX and A549/PTX)were generated.Cell Counting Kit-8(CCK-8)assay was used to detect cell viability.Colony formation assay and flow cytometry were utilized to assess cell proliferation and apop-tosis,respectively.Immunofluorescence staining and TOP/FOP flash luciferase assay were employed to estimateβ-catenin activation.Western blotting was implemented to estimate the protein levels of apoptosis-,proliferation-,and Wnt/β-catenin signaling-associated markers.A xenograft mouse model was established to investigate the impact of SAL on PTX resist-ance in vivo.Results SAL increased PTX-induced suppression of proliferation and promoted apoptosis in PTX-resistant NSCLC cells.SAL blocked the Wnt/β-catenin signaling in A549/PTX cells and in tumor-bearing mice.Activating Wnt/β-catenin signaling reversed the SAL-mediated increase in the sensitivity of NSCLC cells to PTX.SAL attenuated PTX resistance in NSCLC in the xenograft mouse model.Conclusion SAL enhances the sensitivity of NSCLC cells to PTX by blocking the Wnt/β-catenin signal transduction.展开更多
Paclitaxel is one of the commonly used drugs in postoperative chemotherapy for ovarian cancer patients. However, affected by drug dosage and individual differences in the course of medication, patients will have diffe...Paclitaxel is one of the commonly used drugs in postoperative chemotherapy for ovarian cancer patients. However, affected by drug dosage and individual differences in the course of medication, patients will have different degrees of adverse reactions, which will cause damage to the patient’s body once they occur. This paper retrospectively analyzed the clinical data of patients with severe allergic reactions such as fecal incontinence and numbness of hands and feet caused by the use of paclitaxel liposome during postoperative chemotherapy in a case of ovarian cancer admitted to our hospital. The causes and corresponding treatment measures were analyzed, in order to provide the reference for medical staff to take effective countermeasures in advance in the future.展开更多
Various therapeutic modalities have been engineered for lung cancer treatment,but their clinic application is severely impeded by the poor therapy efficiency and immunosuppressive microenvironment.Herein,we fabricated...Various therapeutic modalities have been engineered for lung cancer treatment,but their clinic application is severely impeded by the poor therapy efficiency and immunosuppressive microenvironment.Herein,we fabricated a library of small molecule redox-labile nanoparticles(NPs)(i.e.,diPTX-2C NPs,diPTX-2S NPs,and diPTX-2Se NPs)by the self-assembly of dimer paclitaxel(PTX)prodrug,and then utilized these NPs with the traditional Chinese medicine(TCM)Qi-Yu-San-Long-Fang(Q)for effective chemoimmunotherapy on Lewis lung carcinoma(LLC)-bearing mice models.Under the high concentration of glutathione(GSH)and H_(2)O_(2),diPTX-2Se NPs could specifically release PTX in cancer cells and exert a higher selectivity and toxicity than normal cells.In LLC tumor-bearing mice,oral administration of Q not only effectively downregulated programmed death ligand-1(PD-L1)expression,but also remodeled the immunosuppressive tumor immune microenvironment via the increase of CD4^(+)T and CD8^(+)T cell proportion and the repolarization of M2 into M1 macrophages in tumor tissues,collectively achieving superior synergistic treatment outcomes in combination with intravenous PTX prodrug NPs.Besides,we found that the combination regimen also demonstrated excellent chemoimmunotherapeutic performances on low-dose small established tumor and high-dose large established tumor models.This study may shed light on the potent utilization of Chinese and Western-integrative strategy for efficient tumor chemoimmunotherapy.展开更多
Objective:To construct a pH-responsive paclitaxel(PTX)-exosome composite nanocarrier and investigate its inhibitory effect on the proliferation of endometrial cancer cells(HEC-1A).Methods:PTX was loaded into exosomes ...Objective:To construct a pH-responsive paclitaxel(PTX)-exosome composite nanocarrier and investigate its inhibitory effect on the proliferation of endometrial cancer cells(HEC-1A).Methods:PTX was loaded into exosomes derived from adipose mesenchymal stem cells using the thin-film hydration method,and modified with polyethylene glycol-polylactic-co-glycolic acid(PEG-PLGA)to form nanocarriers(PTX-Exo-NPs).The particle size and morphology were detected by nanoparticle size and Zeta potential analyzer;drug encapsulation efficiency and drug loading capacity were determined by high-performance liquid chromatography;drug release behavior was evaluated in vitro under simulated acidic(pH 5.5)and physiological(pH 7.4)conditions;MTT assay and flow cytometry were used to detect the effects of the carrier on the proliferation,apoptosis,and cell cycle distribution of HEC-1A cells.Results:PTX-Exo-NPs exhibited a uniform spherical shape with a particle size of(128.5±5.2)nm,PTX encapsulation efficiency of 92.3%±2.1%,and drug loading capacity of 15.6%±0.8%.Drug release rate in the acidic environment(85.3%±2.1%within 72 h)was significantly higher than that in the physiological environment(48.0%±1.7%).In vitro experiments demonstrated that the proliferation inhibition rate of PTX-Exo-NPs on HEC-1A cells was higher than that of free PTX,with a lower IC50(0.64μM vs 4.70μM),and could induce cell apoptosis(apoptosis rate:28.7%±2.1%vs 14.2%±1.5%)and promote cell cycle arrest(G_2/M rate:45.3%±3.2%).Conclusion:PTX-Exo-NPs exhibit pH-responsive characteristics,which can target drug release through the acidic microenvironment,enhance the proliferation inhibition and pro-apoptotic effect on endometrial cancer cells,thus serving as a potential strategy for targeted therapy of endometrial tumors.展开更多
Taxus cuspidata,a rare species of the Taxus genus,and its wild resources are under severe threat.The development of cultivated species has become an important strategy to replace wild species.The objective of this wor...Taxus cuspidata,a rare species of the Taxus genus,and its wild resources are under severe threat.The development of cultivated species has become an important strategy to replace wild species.The objective of this work was to elucidate the differences in secondary metabolite accumulation,particularly in the paclitaxel biosynthesis pathway,between wild and cultivated species.This study employed liquid chromatography-tandem mass spectrometry(LC-MS/MS)and RNA sequencing(RNA-Seq)technologies to conduct integrated metabolomic and transcriptomic analyses of wild and cultivated species of T.cuspidata.The results showed that the content of paclitaxel in cultivated species was significantly higher than in wild species,reaching 1.67 times that of the latter(p 0.01).Additionally,the<content of key paclitaxel precursors,GGPP and 10-deacetylbaccatin III,in cultivated species was 1.94 times(p 0.05)<and 1.71 times(p 0.01)higher than in wild species,respectively.Transcriptomic analysis identified 2606 differentially<expressed genes(DEGs),among which key enzyme genes related to paclitaxel biosynthesis(such as DXS,DXR,GGPS,etc.)were generally upregulated in cultivated species.Multiple key enzyme genes in both the 2-C-methyl-D-erythritol 4-phosphate pathway(MEP)and paclitaxel biosynthesis pathways were significantly upregulated in cultivated species.Conversely,genes and metabolites related to sugar metabolism were found to be higher in content in wild species.These findings reveal the significant advantage of cultivated species in paclitaxel production capacity,providing new insights into the metabolic regulation mechanisms during yew domestication.This has important implications for optimizing paclitaxel biosynthesis and guiding future improvements in T.cuspidata cultivars.展开更多
Chemoimmunotherapy has the potential to enhance chemotherapy and modulate the immunosuppressive tumor microenvironment by activating immunogenic cell death(ICD),making it a promising strategy for clinical application....Chemoimmunotherapy has the potential to enhance chemotherapy and modulate the immunosuppressive tumor microenvironment by activating immunogenic cell death(ICD),making it a promising strategy for clinical application.Alantolactone(A)was found to augment the anticancer efficacy of paclitaxel(P)at a molar ratio of 1:0.5(P:A)through induction of more potent ICD via modulation of STAT3 signaling pathways.Nano drug delivery systems can synergistically combine natural drugs with conventional chemotherapeutic agents,thereby enhancing multi-drug chemoimmunotherapy.To improve tumor targeting ability and bioavailability of hydrophobic drugs,an amphiphilic prodrug conjugate(HA-PTX)was chemically modified with paclitaxel(PTX)and hyaluronic acid(HA)as a backbone.Based on this concept,CD44-targeted nanodrugs(A@HAP NPs)were developed for co-delivery of A and P in colorectal cancer treatment,aiming to achieve synergistic toxicity-based chemo-immunotherapy.The uniform size and high drug loading capacity of A@HAP NPs facilitated their accumulation within tumors through enhanced permeability and retention effect as well as HA-mediated targeting,providing a solid foundation for subsequent synergistic therapy and immunoregulation.In vitro and in vivo studies demonstrated that A@HAP NPs exhibited potent cytotoxicity against tumor cells while also remodeling the immune-suppressive tumor microenvironment by promoting antigen presentation and inducing dendritic cell maturation,thus offering a novel approach for colorectal cancer chemoimmunotherapy.展开更多
Self-assembled prodrug nanomedicine has emerged as an advanced platform for antitumor therapy,mainly comprise drug modules,response modules and modification modules.However,existing studies usually compare the differe...Self-assembled prodrug nanomedicine has emerged as an advanced platform for antitumor therapy,mainly comprise drug modules,response modules and modification modules.However,existing studies usually compare the differences between single types of modification modules,neglecting the impact of steric-hindrance effect caused by chemical structure.Herein,single-tailed modification module with low-steric-hindrance effect and two-tailed modification module with high-steric-hindrance effect were selected to construct paclitaxel prodrugs(P-LA_(C18)and P-BAC18),and the in-depth insights of the sterichindrance effect on prodrug nanoassemblies were explored.Notably,the size stability of the two-tailed prodrugs was enhanced due to improved intermolecular interactions and steric hindrance.Single-tailed prodrug nanoassemblies were more susceptible to attack by redox agents,showing faster drug release and stronger antitumor efficacy,but with poorer safety.In contrast,two-tailed prodrug nanoassemblies exhibited significant advantages in terms of pharmacokinetics,tumor accumulation and safety due to the good size stability,thus ensuring equivalent antitumor efficacy at tolerance dose.These findings highlighted the critical role of steric-hindrance effect of the modification module in regulating the structureactivity relationship of prodrug nanoassemblies and proposed new perspectives into the precise design of self-assembled prodrugs for high-performance cancer therapeutics.展开更多
BACKGROUND Chemotherapy combined with anti-angiogenic therapy has become an important strategy for the treatment of advanced gastric cancer(AGC);however,the regimen needs optimization.AIM To evaluate the efficacy of a...BACKGROUND Chemotherapy combined with anti-angiogenic therapy has become an important strategy for the treatment of advanced gastric cancer(AGC);however,the regimen needs optimization.AIM To evaluate the efficacy of albumin-bound paclitaxel(nab-ptx)combined with the small molecule vascular endothelial growth factor inhibitor anlotinib in secondline and beyond treatment of AGC.METHODS We collected data from AGC patients at our hospital who experienced disease progression after first-line chemotherapy and received anlotinib combined with nab-ptx.The primary endpoints included overall survival(OS)and progressionfree survival(PFS),while the secondary endpoints were objective response rate(ORR),disease control rate(DCR),and adverse events(AEs).RESULTS Preliminary results indicated that anlotinib combined with nab-ptx can provide significant efficacy in second-line or above treatment for AGC(median PFS=6.0 months,median OS=12.0 months),with an ORR of 42%and a DCR of 78%.Further analysis revealed that patients who experienced hypertension,proteinuria,and hand-foot syndrome during treatment had better efficacy compared to those who did not experience these AEs.Mechanistic studies suggest that this regimen likely exerts synergistic anti-tumor effects by activating the immune response through the reduction of regulatory T-cell proportions.Common adverse reactions included bone marrow suppression,peripheral neuropathy,hypertension,proteinuria,and hand-foot syndrome,which were manageable and resolved with appropriate interventions,indicating the promising application of this regimen in second-line or above treatment for AGC.CONCLUSION The combination of anlotinib and nab-ptx shows promising efficacy with fewer toxicities in AGC treatment.The regimen holds promise as a second-line treatment of AGC;however,its specific clinical value requires further research.展开更多
Most anti-tumor agents suffer from systemic non-specific distribution and low aggregation in tumors,which not only decreases the therapeutic efficacy,but also causes systemic toxic side effects in the treatments of tu...Most anti-tumor agents suffer from systemic non-specific distribution and low aggregation in tumors,which not only decreases the therapeutic efficacy,but also causes systemic toxic side effects in the treatments of tumors.In recent years,the rapid development of nanotechnology has brought new ideas for the application of anti-tumor drugs.Nanomedicines,such as liposomes and micelles,can improve drug targeting and prolong systemic circulation time to promote anti-tumor efficacy and reduce toxic side effects.However,conventional micelles bear the risk of instability and premature drug leaking in the blood circulation.We designed a reduction-responsive core-cross-linked micelle PTX@Fmoc-LA-PEG efficiently encapsulating Paclitaxel(PTX)viaπ-πstacking and hydrophobic interactions of Fmoc and PTX.Moreover,the micelle was further locked based on the cross-linking properties of the disulfide bonds formed by lipoic acid(LA).As expected,the core-cross-linked micelles PTX@Fmoc-LA-PEG remained stable in normal physiological environments,while restoring the normal drug release rate of micelles under the highly reducing environment due to LA unlocking.The blank micelles(Fmoc-LA-PEG)exhibited excellent biocompatibility,while the drug-loaded micelles(PTX@Fmoc-LA-PEG)displayed a remarkable anti-tumor effect in vitro and in vivo experiments.These results suggested that core-cross-linked micelles PTX@FmocLA-PEG have great potential to improve the targeting and stability of anti-tumor drugs.展开更多
BACKGROUND Abnormal iron metabolism plays a critical role in paclitaxel(PTX)resistance in esophageal cancer cells.Qige San(QG)is a traditional Chinese herbal formula that is reported to improve short-term therapeutic ...BACKGROUND Abnormal iron metabolism plays a critical role in paclitaxel(PTX)resistance in esophageal cancer cells.Qige San(QG)is a traditional Chinese herbal formula that is reported to improve short-term therapeutic effects of esophageal cancer.AIM To investigate the effects and regulatory mechanisms involved in QG-targeted PTX-resistant esophageal cancer cells.METHODS Cell viability was assessed using the Cell Counting Kit-8 assay.Ferroptosis was evaluated by analyzing lipid reactive oxygen species accumulation and the Fe2+concentration in PTX-resistant esophageal cancer cells.Expression of ferroptosis regulators was measured by western blot.Network pharmacology analysis was employed to identify potential targets of QG in PTX-resistant esophageal cancer cells.RESULTS Treatment with QG significantly suppressed the viability,proliferation,and migration of PTX-resistant esophageal cancer cells and simultaneously induced ferroptosis.The network pharmacology analysis identified the phosphoinositide 3-kinase(PI3K)/protein kinase B signaling pathway as the potential target of QG in PTX-resistant esophageal cancer cells.Activation of the PI3K pathway notably reversed the ferroptosis of PTX-resistant esophageal cancer cells that was induced by QG.CONCLUSION QG could repress the resistance of esophageal cancer cells to PTX via targeting the PI3K signaling pathway.展开更多
BACKGROUND Some studies have demonstrated that combination treatment with anlotinib and albumin-bound paclitaxel has superior efficacy in stage IV non-small cell lung cancer(NSCLC).Howbeit,there is limited research on...BACKGROUND Some studies have demonstrated that combination treatment with anlotinib and albumin-bound paclitaxel has superior efficacy in stage IV non-small cell lung cancer(NSCLC).Howbeit,there is limited research on the effects of combination therapy.AIM To determine the efficacy of anlotinib plus albumin-paclitaxel in stage IV NSCLC.METHODS Forty-two patients diagnosed with stage IV NSCLC who were treated at our hospital from January 2022 to February 2023 were selected as study subjects.According to the research protocol,the patients were divided into two groups:conventional therapy(albumin paclitaxel,n=20)and combination therapy(anlotinib plus albumin paclitaxel,n=22).The clinical effect,serum tumor markers,progression-free survival,overall survival,immune function,quality of life,mental state,and toxic side effects were compared between the two groups.RESULTS The disease remission rate,disease control rate,CD3^(+),CD4^(+),CD4^(+)/CD8^(+)and Karnofsky Performance Scale(KPS)score in combined therapy were higher than conventional therapy.After treatment,levels of carcinoembryonic antigen,cytokeratin 19 fragment antigen 21-1,and vascular endothelial growth factor,self-rating anxiety scale,and self-rating depression scale score were all lower in combination therapy compared to conventional therapy.In addition,there was no remarkable difference in adverse reactions between the two groups.CONCLUSION Anlotinib combined with albumin-paclitaxel demonstrated therapeutic efficacy in stage IV NSCLC,reducing depression,anxiety,and tumor biomarker levels,while enhancing immune function,prolonging survival,and improving quality of life.展开更多
BACKGROUND Given the clinical challenges posed by drug-eluting stents,drug-coated balloons offer a promising alternative by delivering antiproliferative medications directly to the vessel wall.AIM To compare the effic...BACKGROUND Given the clinical challenges posed by drug-eluting stents,drug-coated balloons offer a promising alternative by delivering antiproliferative medications directly to the vessel wall.AIM To compare the efficacy of paclitaxel-coated balloon(PCB)angioplasty vs sirolimus-coated balloon(SCB)angioplasty in the treatment of coronary artery disease(CAD),focusing on both in-stent restenosis(ISR)and de-novo lesions(DNL).METHODS A comprehensive literature search on PubMed,EMBASE,and Cochrane Central from inception to 5th February 2025.Only randomized controlled trials and observational studies comparing outcomes of PCB vs SCB angioplasty in patients with ISR or DNL were included.RESULTS A total of nine studies with 1981 patients(949 in PCB arm and 1032 in SCB arm)were included for further quantitative analysis.The results indicated that both PCB and SCB angioplasty are effective in treating CAD,with PCB showing a greater minimal lumen diameter for DNL[mean difference:-0.11(95% confidence interval:-0.22 to-0.01,P=0.03)].However,the risk of target lesion revascularization and diameter stenosis was identical for both PCB and SCB during the 9-12-month follow-up period.CONCLUSION This meta-analysis highlights that PCB angioplasty may offer superior angiographic outcomes compared to SCB angioplasty,specifically in achieving greater minimal lumen diameter in patients with DNL.These findings suggest that while PCB has certain advantages in terms of tissue retention and immediate efficacy,both PCB and SCB are viable options for treating ISR or DNL in CAD patients.Further large-scale studies are required to conclusively determine the long-term benefits and potential risks associated with each type of drug-coated balloons angioplasty.展开更多
Bioresorbable stents(BRS)have emerged as a groundbreaking development in the field of percutaneous coronary intervention(PCI)as they address the long-standing concerns of metallic stents.Nevertheless,the observed high...Bioresorbable stents(BRS)have emerged as a groundbreaking development in the field of percutaneous coronary intervention(PCI)as they address the long-standing concerns of metallic stents.Nevertheless,the observed higher thrombosis rates in the first generation BRS,i.e.ABSORB®,might be attributed to their thicker struts,slower degradation rate and structural dismantling of partially endothelialized stents.In this study,measures have been taken to overcome these limitations include reducing strut thickness,modifying the structural design to maintain radial strength with thinner round cross section struts and using a new material poly(L-lactide-co-ɛ-caprolactone)(PLCL 95/5)that is tougher and degrade faster than poly(L-lactic acid)(PLLA).Given the excellent biocompatibility of PLCL materials,the US FDA has approved their use in clinical applications.PLCL stents can be used to treat diseases such as tracheal stenosis and tracheoesophageal fistula,and can also be applied in the construction of other tissue engineering stents,such as nerve conduitsand fat filling stents.The newly designed coronary stents were fabricated using a 3D printing technology with a rotating platform,coated with a paclitaxel coating and comprehensive in vitro research was conducted.It was the first to undergo tests in animals.Results showed the novel paclitaxel eluting PLCL stents had super-flexible structure,thinner round cross-sectional struts,a faster degradation profile and satisfactory hemocompatibility.With a paclitaxel dose of 0.57μg/mm^(2),the drug eluting stents showed very low degree of stenosis within 6 months of implantation in a porcine model.Overall,the results showed that the novel 3D printed PLCL drug eluting stent is a very promising candidate for next generation bioresorbable coronary stent.展开更多
Objectives:Due to systematic side effects,there is a growing interest in nanoparticle formulation of anticancer drugs.Here,we aimed to synthesize poly(styrene-alt-maleic anhydride)cross-linked by melamine(PSMA/Me)and ...Objectives:Due to systematic side effects,there is a growing interest in nanoparticle formulation of anticancer drugs.Here,we aimed to synthesize poly(styrene-alt-maleic anhydride)cross-linked by melamine(PSMA/Me)and coated with magnetite nanoparticles(MNPs)PSMA/Me/Fe_(3)O_(4).In addition,we aimed to load paclitaxel(PTX)into PSMA/Me/Fe_(3)O_(4)for drug delivery and anticancer investigations.Methods:Novel PSMA/Me was synthesized via free radical copolymerization,coated with Fe_(3)O_(4),and then used as a transporter for PTX delivery.Fabricated copolymer was characterized using SEM,TGA,and XRD techniques.Drug release rate and loading efficiency were investigated.Human ovarian cancer cells(Skov-3)and breast cancer cells(MCF-7 cells)were incubated with the serial concentration of either free PTX or PSMA/Me/Fe_(3)O_(4)/PTX for cell viability and IC_(50)analysis for 24 and 48 h.Results:Characterization methods confirmed PSMA/Me copolymer formation.The results showed a significant encapsulation efficiency of 83%.The drug release analysis exhibited that PSMA/Me/Fe_(3)O_(4)/PTX may be considered pH-sensitive nanocarriers.PSMA/Me/Fe_(3)O_(4)/PTX reduced cell viability both dose and time-dependently(p<0.05).IC50 values of PSMA/Me/Fe_(3)O_(4)/PTX were low when compared to free PTX either 24 or 48 h post-treatment.Conclusions:Our results indicated that PSMA/Me/Fe_(3)O_(4)/PTX was more cytotoxic than PTX in both cancer cells.Findings indicated the potential of PSMA/Me/Fe_(3)O_(4)/PTX as an anticancer nanocarrier system.展开更多
The preparation of polymer-anticancer drug conjugates is an effective way to improve the efficacy and decrease the toxicity of anticancer drugs. Polymer-drug conjugates, which were made by combining a suitable polymer...The preparation of polymer-anticancer drug conjugates is an effective way to improve the efficacy and decrease the toxicity of anticancer drugs. Polymer-drug conjugates, which were made by combining a suitable polymeric carrier, a biodegradable linker and a bioactive anticancer agent, could form the basis of a new generation of anticancer agents. Poly （L-glutamic acid）- paclitaxel conjugate is a polymer-drug conjugate that links anticancer agent paclitaxel （PTX） to poly （L-glutamic acid） （PG）. PG-PTX conjugate can improve the anticancer activity, enhance the safety and efficacy, and improve the pharmacokinetic properties of PTX. Therefore, the application of PG-PTX facilitates the clinical therapy of a variety of human cancers.展开更多
The objective of this study was to prepare and characterize paclitaxel-polyvinylpyrrolidone （PTX-PVP） solid dispersions with the intention of improving its solubility and dissolution properties. The PTX-PVP solid di...The objective of this study was to prepare and characterize paclitaxel-polyvinylpyrrolidone （PTX-PVP） solid dispersions with the intention of improving its solubility and dissolution properties. The PTX-PVP solid dispersion systems were prepared by solvent method. The release rate ofpaclitaxel was determined from dissolution studies and the physicochemical properties of solid dispersion were investigated by differential scanning calorimetry （DSC）, powder X-ray diffraction （PXRD） and scanning electron microscopy （SEM）. The cytotoxicities ofpaclitaxel in solid dispersion to the SKOV-3 cells were assayed by a SRB staining method. The results showed that the solubility and dissolution rate of paclitaxel were significantly improved in solid dispersion system compared with that of the pure drug and physical mixture. The results of DSC and PXRD showed that the paclitaxel in solid dispersion was amorphous form. No paclitaxel crystals in the solid dispersions was found during SEM analysis. Cytotoxicity study suggested that the inhibitory rates of PTX-PVP solid dispersion to SKOV-3 cells were higher than that of pure paclitaxel. The solubility and dissolution of paclitaxel were improved by solid dispersion technique. In vitro cytotoxicity of paclitaxel in solid dispersion was higher than that of pure drug.展开更多
A sensitive and selective method has been developed and validated for the quantitation of paclitaxel in human plasma by liquid chromatography-electrospray ionization mass spectrometry （LC-ESI-MS）. Paclitaxel and nor...A sensitive and selective method has been developed and validated for the quantitation of paclitaxel in human plasma by liquid chromatography-electrospray ionization mass spectrometry （LC-ESI-MS）. Paclitaxel and norethindrone （used as internal standard, I.S.） were extracted from human plasma by a one-step liquid-liquid extraction with t-butyl methyl ether. Separation on a Zorbax SB-C18 column （100 mm×2.1 mm, 3.5 μm, Agilent） was achieved by gradient elution with methanol and 0.2 mmol/L ammonium formate containing 0.1% formic acid. The selected-ion monitoring （SIM） targeted ions of [M＋Na] at m/z 876.5 for paclitaxel and [M＋H] at m/z 299.4 for I.S. The assay was validated in the range of 1.0-400 ng/mL （r〉0.998） with LLOQ of 1.0 ng/mL. Intra- and inter-day precisions were all less than 9.0%, with accuracies of ＋6.8%. The method was successfully applied to evaluate the pharmacokinetics of paclitaxel liposome for injection in patients.展开更多
Objective： To observe the efficacy and safety of albumin-bound paclitaxel （ABP） monotherapy in treating recurrent advanced non-small-cell lung cancer （NSCLC）. Methods： We retrospectively analyzed the short-term ...Objective： To observe the efficacy and safety of albumin-bound paclitaxel （ABP） monotherapy in treating recurrent advanced non-small-cell lung cancer （NSCLC）. Methods： We retrospectively analyzed the short-term efficacy and toxicities of ABP monotherapy in treating 21 patients who had previously undergone multiple cycles of therapy for their advanced NSCLC in our hospital since 2010. The treatment-related survival was also analyzed. Results： Of these 21 patients, the best overall response was partial response （PR） in 6 patients （28.6%）, stable disease （SD） in I0 patients （47.6%）, and progressive disease （PD） in 5 patients （23.8%）. The overall response rate （ORR） was 28.6% and the disease control rate （DCR） （PR ＋ SD） was 76.2%. The median progression-flee survival （PFS） was 4.0 months （95% CI, 5.0-7.0 months）. The main grade 3/4 toxicities included neutropenia （11.1%）, peripheral nerve toxicity （5.6%）, muscle and joint aches （5.6%）, and fatigue （5.6%）. Conclusions： The ABP monotherapy can achieve good objective response in advanced NSCLC patients who have previously received multiple cycles of treatment and be well tolerated.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant No.82172840)Gusu Health Talents Project of Suzhou Municipal Health Commission(Grant Nos.GSWS2023007 and GSWS2022062)+2 种基金Suzhou Science and Technology Development Plan Project(Grant No.SYW2024005)Chinese Pharmaceutical Association Hospital Pharmacy Department(Grant No.CPA-Z05-ZC-2024002)Jiangsu Research Hospital Association for Precision Medication(Grant No.JY202202).
文摘Objectives:Acquired resistance to paclitaxel represents a critical barrier to the effective chemotherapy of non-small cell lung cancer(NSCLC).The present study aimed to elucidate the molecular and pharmacological mechanisms promoting paclitaxel resistance in NSCLC and to explore potential strategies for overcoming this resistance.Methods:Here,we report an integrated pharmacological and analytical approach to quantify paclitaxel disposition and overcome resistance in a A549/TAX cell model(paclitaxel-resistant A549 cells).Results:Cell counting kit-8(CCK-8)assay,colony formation,and apoptosis assays confirmed that A549/TAX cells exhibited marked resistance to paclitaxel relative to parental A549 cells.Based on transcriptome profiling by RNA sequencing analysis and validation by western blotting assay,we found that the expression of the ATP-binding cassette subfamily B member 1(ABCB1)(the encoded protein is termed P-glycoprotein)was significantly upregulated in resistant cells.By using ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),we demonstrated that ABCB1 overexpression promotes enhanced efflux of intracellular paclitaxel,thereby lowering its cytotoxic accumulation.Genetic silencing of ABCB1 or pharmacological inhibition with the specific P-glycoprotein modulator elacridar or tariquidar restored intracellular paclitaxel levels,as determined by UPLC-MS/MS,and synergistically decreased cell viability as observed in CCK-8 assay.Conclusion:These findings reveal that the ABCB1-mediated drug efflux is a crucial mechanism underlying paclitaxel resistance in NSCLC cells,with UPLC-MS/MS serving as a sensitive analytical method to detect paclitaxel concentration.Inhibition of ABCB1 is a promising therapeutic strategy to resensitize resistant tumor cells to paclitaxel.
基金supported by the National Natural Science Foundation of China(Nos.82225047,82170274,82304665)the National Key Research and Development Program of China(No.2022YFC3501703)+3 种基金Zhejiang Provincial Natural Science Foundation of China(Nos.LZ24H280003,LQ23H280016)the Postdoctoral Fellowship Program of CPSF(No.GZC20233561)the Basic Medical Research Project of Naval Medical University(No.2023QN022)the Key Project at Central Government Level:The Ability Establishment of Sustainable Use for Valuable Chinese Medicine Resources(No.2060302).
文摘Paclitaxel(PTX),a valuable natural product derived from Taxus species,exhibits remarkable anti-cancer properties.It penetrates nanopores in microtubule walls,interacting with tubulin on the lumen surface and disrupting microtubule dynamics,thereby inducing cytotoxic effects in cancer cells.PTX and its derivatives have gained approval for treating various diseases due to their low toxicity,high efficiency,and broad-spectrum application.The widespread success and expanding applications of PTX have led to increased demand,raising concerns about accessibility.Consequently,researchers globally have focused on developing alternative production methods and applying nanocarriers in PTX delivery systems to enhance bioavailability.This review examines the challenges and advancements in PTX sourcing,production,physicochemical properties,anti-cancer mechanisms,clinical applications,trials,and chemo-immunotherapy.It aims to provide a comprehensive reference for the rational development and effective utilization of PTX.
基金supported by the Scientific Research Project of Hubei Cancer Hospital(No.2024HBCHYN08)the Natural Science Foundation of Hubei Province(No.2023AFB988)+1 种基金the Scientific Research Project in the Field of Oncology(No.FB2024025225)the Talent Project of Hubei Cancer Hospital(No.2025HBCHHHRC007).
文摘Objective Chemoresistance,such as paclitaxel(PTX)resistance,has become a great obstacle in non-small cell lung cancer(NSCLC)treatment.The natural agent salidroside(SAL)has been shown to exert an antitumor effect on NSCLC.Nonethe-less,it is unclear whether SAL can decrease the resistance of NSCLC to PTX.Methods PTX-resistant NSCLC cells(H1299/PTX and A549/PTX)were generated.Cell Counting Kit-8(CCK-8)assay was used to detect cell viability.Colony formation assay and flow cytometry were utilized to assess cell proliferation and apop-tosis,respectively.Immunofluorescence staining and TOP/FOP flash luciferase assay were employed to estimateβ-catenin activation.Western blotting was implemented to estimate the protein levels of apoptosis-,proliferation-,and Wnt/β-catenin signaling-associated markers.A xenograft mouse model was established to investigate the impact of SAL on PTX resist-ance in vivo.Results SAL increased PTX-induced suppression of proliferation and promoted apoptosis in PTX-resistant NSCLC cells.SAL blocked the Wnt/β-catenin signaling in A549/PTX cells and in tumor-bearing mice.Activating Wnt/β-catenin signaling reversed the SAL-mediated increase in the sensitivity of NSCLC cells to PTX.SAL attenuated PTX resistance in NSCLC in the xenograft mouse model.Conclusion SAL enhances the sensitivity of NSCLC cells to PTX by blocking the Wnt/β-catenin signal transduction.
文摘Paclitaxel is one of the commonly used drugs in postoperative chemotherapy for ovarian cancer patients. However, affected by drug dosage and individual differences in the course of medication, patients will have different degrees of adverse reactions, which will cause damage to the patient’s body once they occur. This paper retrospectively analyzed the clinical data of patients with severe allergic reactions such as fecal incontinence and numbness of hands and feet caused by the use of paclitaxel liposome during postoperative chemotherapy in a case of ovarian cancer admitted to our hospital. The causes and corresponding treatment measures were analyzed, in order to provide the reference for medical staff to take effective countermeasures in advance in the future.
基金supported by the Young Elite Scientists Sponsorship Program by China Association of Chinese Medicine(CACM),China(Grant No.:2022-QNRC2-B12)the Key Project of Anhui Province Department of Education,China(Grant Nos.:2023AH030070,2024AH051040,and 2022AH050528)+1 种基金Anhui Province Key Laboratory,China(Grant Nos.:KFKT202305,2024ZYFBAHKLA11,and 2024ZYFBAHKLA15)Greater Health Research Institute of Hefei Comprehensive National Science Center,China(Grant No.:2023CXMMTCM005).
文摘Various therapeutic modalities have been engineered for lung cancer treatment,but their clinic application is severely impeded by the poor therapy efficiency and immunosuppressive microenvironment.Herein,we fabricated a library of small molecule redox-labile nanoparticles(NPs)(i.e.,diPTX-2C NPs,diPTX-2S NPs,and diPTX-2Se NPs)by the self-assembly of dimer paclitaxel(PTX)prodrug,and then utilized these NPs with the traditional Chinese medicine(TCM)Qi-Yu-San-Long-Fang(Q)for effective chemoimmunotherapy on Lewis lung carcinoma(LLC)-bearing mice models.Under the high concentration of glutathione(GSH)and H_(2)O_(2),diPTX-2Se NPs could specifically release PTX in cancer cells and exert a higher selectivity and toxicity than normal cells.In LLC tumor-bearing mice,oral administration of Q not only effectively downregulated programmed death ligand-1(PD-L1)expression,but also remodeled the immunosuppressive tumor immune microenvironment via the increase of CD4^(+)T and CD8^(+)T cell proportion and the repolarization of M2 into M1 macrophages in tumor tissues,collectively achieving superior synergistic treatment outcomes in combination with intravenous PTX prodrug NPs.Besides,we found that the combination regimen also demonstrated excellent chemoimmunotherapeutic performances on low-dose small established tumor and high-dose large established tumor models.This study may shed light on the potent utilization of Chinese and Western-integrative strategy for efficient tumor chemoimmunotherapy.
文摘Objective:To construct a pH-responsive paclitaxel(PTX)-exosome composite nanocarrier and investigate its inhibitory effect on the proliferation of endometrial cancer cells(HEC-1A).Methods:PTX was loaded into exosomes derived from adipose mesenchymal stem cells using the thin-film hydration method,and modified with polyethylene glycol-polylactic-co-glycolic acid(PEG-PLGA)to form nanocarriers(PTX-Exo-NPs).The particle size and morphology were detected by nanoparticle size and Zeta potential analyzer;drug encapsulation efficiency and drug loading capacity were determined by high-performance liquid chromatography;drug release behavior was evaluated in vitro under simulated acidic(pH 5.5)and physiological(pH 7.4)conditions;MTT assay and flow cytometry were used to detect the effects of the carrier on the proliferation,apoptosis,and cell cycle distribution of HEC-1A cells.Results:PTX-Exo-NPs exhibited a uniform spherical shape with a particle size of(128.5±5.2)nm,PTX encapsulation efficiency of 92.3%±2.1%,and drug loading capacity of 15.6%±0.8%.Drug release rate in the acidic environment(85.3%±2.1%within 72 h)was significantly higher than that in the physiological environment(48.0%±1.7%).In vitro experiments demonstrated that the proliferation inhibition rate of PTX-Exo-NPs on HEC-1A cells was higher than that of free PTX,with a lower IC50(0.64μM vs 4.70μM),and could induce cell apoptosis(apoptosis rate:28.7%±2.1%vs 14.2%±1.5%)and promote cell cycle arrest(G_2/M rate:45.3%±3.2%).Conclusion:PTX-Exo-NPs exhibit pH-responsive characteristics,which can target drug release through the acidic microenvironment,enhance the proliferation inhibition and pro-apoptotic effect on endometrial cancer cells,thus serving as a potential strategy for targeted therapy of endometrial tumors.
基金supported by grants from the National Science Foundation of China to Yanwen Zhang(32272757,31972363)grants from Liaoning Provincial Department of Education Project to Dandan Wang(JYTMS20230698)grants from the Liaoning Provincial Science and Technology.Fund Project to Dandan Wang(2023JH2/101700200).
文摘Taxus cuspidata,a rare species of the Taxus genus,and its wild resources are under severe threat.The development of cultivated species has become an important strategy to replace wild species.The objective of this work was to elucidate the differences in secondary metabolite accumulation,particularly in the paclitaxel biosynthesis pathway,between wild and cultivated species.This study employed liquid chromatography-tandem mass spectrometry(LC-MS/MS)and RNA sequencing(RNA-Seq)technologies to conduct integrated metabolomic and transcriptomic analyses of wild and cultivated species of T.cuspidata.The results showed that the content of paclitaxel in cultivated species was significantly higher than in wild species,reaching 1.67 times that of the latter(p 0.01).Additionally,the<content of key paclitaxel precursors,GGPP and 10-deacetylbaccatin III,in cultivated species was 1.94 times(p 0.05)<and 1.71 times(p 0.01)higher than in wild species,respectively.Transcriptomic analysis identified 2606 differentially<expressed genes(DEGs),among which key enzyme genes related to paclitaxel biosynthesis(such as DXS,DXR,GGPS,etc.)were generally upregulated in cultivated species.Multiple key enzyme genes in both the 2-C-methyl-D-erythritol 4-phosphate pathway(MEP)and paclitaxel biosynthesis pathways were significantly upregulated in cultivated species.Conversely,genes and metabolites related to sugar metabolism were found to be higher in content in wild species.These findings reveal the significant advantage of cultivated species in paclitaxel production capacity,providing new insights into the metabolic regulation mechanisms during yew domestication.This has important implications for optimizing paclitaxel biosynthesis and guiding future improvements in T.cuspidata cultivars.
基金supported by Zhejiang Provincial Natural Science Foundation(LYY22H300001,LGF22H150016)Wenzhou Municipal Science and Technology Bureau(Y20210212)+2 种基金Application Basic Research Project of Liaoning Provincial Department of Science and Technology(2023JH2/101700072)Zhejiang Medical Doctor Association(YS2022-2-001)Health innovation talents program(Longfa Kou)from Health Commission of Zhejiang Province.
文摘Chemoimmunotherapy has the potential to enhance chemotherapy and modulate the immunosuppressive tumor microenvironment by activating immunogenic cell death(ICD),making it a promising strategy for clinical application.Alantolactone(A)was found to augment the anticancer efficacy of paclitaxel(P)at a molar ratio of 1:0.5(P:A)through induction of more potent ICD via modulation of STAT3 signaling pathways.Nano drug delivery systems can synergistically combine natural drugs with conventional chemotherapeutic agents,thereby enhancing multi-drug chemoimmunotherapy.To improve tumor targeting ability and bioavailability of hydrophobic drugs,an amphiphilic prodrug conjugate(HA-PTX)was chemically modified with paclitaxel(PTX)and hyaluronic acid(HA)as a backbone.Based on this concept,CD44-targeted nanodrugs(A@HAP NPs)were developed for co-delivery of A and P in colorectal cancer treatment,aiming to achieve synergistic toxicity-based chemo-immunotherapy.The uniform size and high drug loading capacity of A@HAP NPs facilitated their accumulation within tumors through enhanced permeability and retention effect as well as HA-mediated targeting,providing a solid foundation for subsequent synergistic therapy and immunoregulation.In vitro and in vivo studies demonstrated that A@HAP NPs exhibited potent cytotoxicity against tumor cells while also remodeling the immune-suppressive tumor microenvironment by promoting antigen presentation and inducing dendritic cell maturation,thus offering a novel approach for colorectal cancer chemoimmunotherapy.
基金supported by the National Natural Science Foundation of China,(Nos.82272151,82204318)Liaoning Revitalization Talents Program(No.XLYC2203083)+2 种基金Shenyang Young and Middle-aged Science and Technology Innovation Talent Support Program(No.RC220389)Postdoctoral Fellowship Program of CPSF(No.GZC20231732)China Postdoctoral Science Foundation(Nos.2023TQ0222,2023MD744229).
文摘Self-assembled prodrug nanomedicine has emerged as an advanced platform for antitumor therapy,mainly comprise drug modules,response modules and modification modules.However,existing studies usually compare the differences between single types of modification modules,neglecting the impact of steric-hindrance effect caused by chemical structure.Herein,single-tailed modification module with low-steric-hindrance effect and two-tailed modification module with high-steric-hindrance effect were selected to construct paclitaxel prodrugs(P-LA_(C18)and P-BAC18),and the in-depth insights of the sterichindrance effect on prodrug nanoassemblies were explored.Notably,the size stability of the two-tailed prodrugs was enhanced due to improved intermolecular interactions and steric hindrance.Single-tailed prodrug nanoassemblies were more susceptible to attack by redox agents,showing faster drug release and stronger antitumor efficacy,but with poorer safety.In contrast,two-tailed prodrug nanoassemblies exhibited significant advantages in terms of pharmacokinetics,tumor accumulation and safety due to the good size stability,thus ensuring equivalent antitumor efficacy at tolerance dose.These findings highlighted the critical role of steric-hindrance effect of the modification module in regulating the structureactivity relationship of prodrug nanoassemblies and proposed new perspectives into the precise design of self-assembled prodrugs for high-performance cancer therapeutics.
基金Supported by Natural Science Foundation of Hubei Province,No.2019CFC929.
文摘BACKGROUND Chemotherapy combined with anti-angiogenic therapy has become an important strategy for the treatment of advanced gastric cancer(AGC);however,the regimen needs optimization.AIM To evaluate the efficacy of albumin-bound paclitaxel(nab-ptx)combined with the small molecule vascular endothelial growth factor inhibitor anlotinib in secondline and beyond treatment of AGC.METHODS We collected data from AGC patients at our hospital who experienced disease progression after first-line chemotherapy and received anlotinib combined with nab-ptx.The primary endpoints included overall survival(OS)and progressionfree survival(PFS),while the secondary endpoints were objective response rate(ORR),disease control rate(DCR),and adverse events(AEs).RESULTS Preliminary results indicated that anlotinib combined with nab-ptx can provide significant efficacy in second-line or above treatment for AGC(median PFS=6.0 months,median OS=12.0 months),with an ORR of 42%and a DCR of 78%.Further analysis revealed that patients who experienced hypertension,proteinuria,and hand-foot syndrome during treatment had better efficacy compared to those who did not experience these AEs.Mechanistic studies suggest that this regimen likely exerts synergistic anti-tumor effects by activating the immune response through the reduction of regulatory T-cell proportions.Common adverse reactions included bone marrow suppression,peripheral neuropathy,hypertension,proteinuria,and hand-foot syndrome,which were manageable and resolved with appropriate interventions,indicating the promising application of this regimen in second-line or above treatment for AGC.CONCLUSION The combination of anlotinib and nab-ptx shows promising efficacy with fewer toxicities in AGC treatment.The regimen holds promise as a second-line treatment of AGC;however,its specific clinical value requires further research.
基金supported by CAMS Innovation Fund for Medical Sciences(No.2021-I2M-1-026)the Postdoctoral Fellowship Program of CPSF(No.GZC20230313)。
文摘Most anti-tumor agents suffer from systemic non-specific distribution and low aggregation in tumors,which not only decreases the therapeutic efficacy,but also causes systemic toxic side effects in the treatments of tumors.In recent years,the rapid development of nanotechnology has brought new ideas for the application of anti-tumor drugs.Nanomedicines,such as liposomes and micelles,can improve drug targeting and prolong systemic circulation time to promote anti-tumor efficacy and reduce toxic side effects.However,conventional micelles bear the risk of instability and premature drug leaking in the blood circulation.We designed a reduction-responsive core-cross-linked micelle PTX@Fmoc-LA-PEG efficiently encapsulating Paclitaxel(PTX)viaπ-πstacking and hydrophobic interactions of Fmoc and PTX.Moreover,the micelle was further locked based on the cross-linking properties of the disulfide bonds formed by lipoic acid(LA).As expected,the core-cross-linked micelles PTX@Fmoc-LA-PEG remained stable in normal physiological environments,while restoring the normal drug release rate of micelles under the highly reducing environment due to LA unlocking.The blank micelles(Fmoc-LA-PEG)exhibited excellent biocompatibility,while the drug-loaded micelles(PTX@Fmoc-LA-PEG)displayed a remarkable anti-tumor effect in vitro and in vivo experiments.These results suggested that core-cross-linked micelles PTX@FmocLA-PEG have great potential to improve the targeting and stability of anti-tumor drugs.
基金Supported by Zhejiang Traditional Chinese Medicine Administration,No.2024ZL944.
文摘BACKGROUND Abnormal iron metabolism plays a critical role in paclitaxel(PTX)resistance in esophageal cancer cells.Qige San(QG)is a traditional Chinese herbal formula that is reported to improve short-term therapeutic effects of esophageal cancer.AIM To investigate the effects and regulatory mechanisms involved in QG-targeted PTX-resistant esophageal cancer cells.METHODS Cell viability was assessed using the Cell Counting Kit-8 assay.Ferroptosis was evaluated by analyzing lipid reactive oxygen species accumulation and the Fe2+concentration in PTX-resistant esophageal cancer cells.Expression of ferroptosis regulators was measured by western blot.Network pharmacology analysis was employed to identify potential targets of QG in PTX-resistant esophageal cancer cells.RESULTS Treatment with QG significantly suppressed the viability,proliferation,and migration of PTX-resistant esophageal cancer cells and simultaneously induced ferroptosis.The network pharmacology analysis identified the phosphoinositide 3-kinase(PI3K)/protein kinase B signaling pathway as the potential target of QG in PTX-resistant esophageal cancer cells.Activation of the PI3K pathway notably reversed the ferroptosis of PTX-resistant esophageal cancer cells that was induced by QG.CONCLUSION QG could repress the resistance of esophageal cancer cells to PTX via targeting the PI3K signaling pathway.
基金Supported by Zhangjiakou Key R&D Program Projects,No.2021108D.
文摘BACKGROUND Some studies have demonstrated that combination treatment with anlotinib and albumin-bound paclitaxel has superior efficacy in stage IV non-small cell lung cancer(NSCLC).Howbeit,there is limited research on the effects of combination therapy.AIM To determine the efficacy of anlotinib plus albumin-paclitaxel in stage IV NSCLC.METHODS Forty-two patients diagnosed with stage IV NSCLC who were treated at our hospital from January 2022 to February 2023 were selected as study subjects.According to the research protocol,the patients were divided into two groups:conventional therapy(albumin paclitaxel,n=20)and combination therapy(anlotinib plus albumin paclitaxel,n=22).The clinical effect,serum tumor markers,progression-free survival,overall survival,immune function,quality of life,mental state,and toxic side effects were compared between the two groups.RESULTS The disease remission rate,disease control rate,CD3^(+),CD4^(+),CD4^(+)/CD8^(+)and Karnofsky Performance Scale(KPS)score in combined therapy were higher than conventional therapy.After treatment,levels of carcinoembryonic antigen,cytokeratin 19 fragment antigen 21-1,and vascular endothelial growth factor,self-rating anxiety scale,and self-rating depression scale score were all lower in combination therapy compared to conventional therapy.In addition,there was no remarkable difference in adverse reactions between the two groups.CONCLUSION Anlotinib combined with albumin-paclitaxel demonstrated therapeutic efficacy in stage IV NSCLC,reducing depression,anxiety,and tumor biomarker levels,while enhancing immune function,prolonging survival,and improving quality of life.
文摘BACKGROUND Given the clinical challenges posed by drug-eluting stents,drug-coated balloons offer a promising alternative by delivering antiproliferative medications directly to the vessel wall.AIM To compare the efficacy of paclitaxel-coated balloon(PCB)angioplasty vs sirolimus-coated balloon(SCB)angioplasty in the treatment of coronary artery disease(CAD),focusing on both in-stent restenosis(ISR)and de-novo lesions(DNL).METHODS A comprehensive literature search on PubMed,EMBASE,and Cochrane Central from inception to 5th February 2025.Only randomized controlled trials and observational studies comparing outcomes of PCB vs SCB angioplasty in patients with ISR or DNL were included.RESULTS A total of nine studies with 1981 patients(949 in PCB arm and 1032 in SCB arm)were included for further quantitative analysis.The results indicated that both PCB and SCB angioplasty are effective in treating CAD,with PCB showing a greater minimal lumen diameter for DNL[mean difference:-0.11(95% confidence interval:-0.22 to-0.01,P=0.03)].However,the risk of target lesion revascularization and diameter stenosis was identical for both PCB and SCB during the 9-12-month follow-up period.CONCLUSION This meta-analysis highlights that PCB angioplasty may offer superior angiographic outcomes compared to SCB angioplasty,specifically in achieving greater minimal lumen diameter in patients with DNL.These findings suggest that while PCB has certain advantages in terms of tissue retention and immediate efficacy,both PCB and SCB are viable options for treating ISR or DNL in CAD patients.Further large-scale studies are required to conclusively determine the long-term benefits and potential risks associated with each type of drug-coated balloons angioplasty.
文摘Bioresorbable stents(BRS)have emerged as a groundbreaking development in the field of percutaneous coronary intervention(PCI)as they address the long-standing concerns of metallic stents.Nevertheless,the observed higher thrombosis rates in the first generation BRS,i.e.ABSORB®,might be attributed to their thicker struts,slower degradation rate and structural dismantling of partially endothelialized stents.In this study,measures have been taken to overcome these limitations include reducing strut thickness,modifying the structural design to maintain radial strength with thinner round cross section struts and using a new material poly(L-lactide-co-ɛ-caprolactone)(PLCL 95/5)that is tougher and degrade faster than poly(L-lactic acid)(PLLA).Given the excellent biocompatibility of PLCL materials,the US FDA has approved their use in clinical applications.PLCL stents can be used to treat diseases such as tracheal stenosis and tracheoesophageal fistula,and can also be applied in the construction of other tissue engineering stents,such as nerve conduitsand fat filling stents.The newly designed coronary stents were fabricated using a 3D printing technology with a rotating platform,coated with a paclitaxel coating and comprehensive in vitro research was conducted.It was the first to undergo tests in animals.Results showed the novel paclitaxel eluting PLCL stents had super-flexible structure,thinner round cross-sectional struts,a faster degradation profile and satisfactory hemocompatibility.With a paclitaxel dose of 0.57μg/mm^(2),the drug eluting stents showed very low degree of stenosis within 6 months of implantation in a porcine model.Overall,the results showed that the novel 3D printed PLCL drug eluting stent is a very promising candidate for next generation bioresorbable coronary stent.
文摘Objectives:Due to systematic side effects,there is a growing interest in nanoparticle formulation of anticancer drugs.Here,we aimed to synthesize poly(styrene-alt-maleic anhydride)cross-linked by melamine(PSMA/Me)and coated with magnetite nanoparticles(MNPs)PSMA/Me/Fe_(3)O_(4).In addition,we aimed to load paclitaxel(PTX)into PSMA/Me/Fe_(3)O_(4)for drug delivery and anticancer investigations.Methods:Novel PSMA/Me was synthesized via free radical copolymerization,coated with Fe_(3)O_(4),and then used as a transporter for PTX delivery.Fabricated copolymer was characterized using SEM,TGA,and XRD techniques.Drug release rate and loading efficiency were investigated.Human ovarian cancer cells(Skov-3)and breast cancer cells(MCF-7 cells)were incubated with the serial concentration of either free PTX or PSMA/Me/Fe_(3)O_(4)/PTX for cell viability and IC_(50)analysis for 24 and 48 h.Results:Characterization methods confirmed PSMA/Me copolymer formation.The results showed a significant encapsulation efficiency of 83%.The drug release analysis exhibited that PSMA/Me/Fe_(3)O_(4)/PTX may be considered pH-sensitive nanocarriers.PSMA/Me/Fe_(3)O_(4)/PTX reduced cell viability both dose and time-dependently(p<0.05).IC50 values of PSMA/Me/Fe_(3)O_(4)/PTX were low when compared to free PTX either 24 or 48 h post-treatment.Conclusions:Our results indicated that PSMA/Me/Fe_(3)O_(4)/PTX was more cytotoxic than PTX in both cancer cells.Findings indicated the potential of PSMA/Me/Fe_(3)O_(4)/PTX as an anticancer nanocarrier system.
基金National Key Technologies R&D Program for New Drugs(Grant No.2009ZX09301-002,2009ZX09304-004).
文摘The preparation of polymer-anticancer drug conjugates is an effective way to improve the efficacy and decrease the toxicity of anticancer drugs. Polymer-drug conjugates, which were made by combining a suitable polymeric carrier, a biodegradable linker and a bioactive anticancer agent, could form the basis of a new generation of anticancer agents. Poly （L-glutamic acid）- paclitaxel conjugate is a polymer-drug conjugate that links anticancer agent paclitaxel （PTX） to poly （L-glutamic acid） （PG）. PG-PTX conjugate can improve the anticancer activity, enhance the safety and efficacy, and improve the pharmacokinetic properties of PTX. Therefore, the application of PG-PTX facilitates the clinical therapy of a variety of human cancers.
文摘The objective of this study was to prepare and characterize paclitaxel-polyvinylpyrrolidone （PTX-PVP） solid dispersions with the intention of improving its solubility and dissolution properties. The PTX-PVP solid dispersion systems were prepared by solvent method. The release rate ofpaclitaxel was determined from dissolution studies and the physicochemical properties of solid dispersion were investigated by differential scanning calorimetry （DSC）, powder X-ray diffraction （PXRD） and scanning electron microscopy （SEM）. The cytotoxicities ofpaclitaxel in solid dispersion to the SKOV-3 cells were assayed by a SRB staining method. The results showed that the solubility and dissolution rate of paclitaxel were significantly improved in solid dispersion system compared with that of the pure drug and physical mixture. The results of DSC and PXRD showed that the paclitaxel in solid dispersion was amorphous form. No paclitaxel crystals in the solid dispersions was found during SEM analysis. Cytotoxicity study suggested that the inhibitory rates of PTX-PVP solid dispersion to SKOV-3 cells were higher than that of pure paclitaxel. The solubility and dissolution of paclitaxel were improved by solid dispersion technique. In vitro cytotoxicity of paclitaxel in solid dispersion was higher than that of pure drug.
文摘A sensitive and selective method has been developed and validated for the quantitation of paclitaxel in human plasma by liquid chromatography-electrospray ionization mass spectrometry （LC-ESI-MS）. Paclitaxel and norethindrone （used as internal standard, I.S.） were extracted from human plasma by a one-step liquid-liquid extraction with t-butyl methyl ether. Separation on a Zorbax SB-C18 column （100 mm×2.1 mm, 3.5 μm, Agilent） was achieved by gradient elution with methanol and 0.2 mmol/L ammonium formate containing 0.1% formic acid. The selected-ion monitoring （SIM） targeted ions of [M＋Na] at m/z 876.5 for paclitaxel and [M＋H] at m/z 299.4 for I.S. The assay was validated in the range of 1.0-400 ng/mL （r〉0.998） with LLOQ of 1.0 ng/mL. Intra- and inter-day precisions were all less than 9.0%, with accuracies of ＋6.8%. The method was successfully applied to evaluate the pharmacokinetics of paclitaxel liposome for injection in patients.
文摘Objective： To observe the efficacy and safety of albumin-bound paclitaxel （ABP） monotherapy in treating recurrent advanced non-small-cell lung cancer （NSCLC）. Methods： We retrospectively analyzed the short-term efficacy and toxicities of ABP monotherapy in treating 21 patients who had previously undergone multiple cycles of therapy for their advanced NSCLC in our hospital since 2010. The treatment-related survival was also analyzed. Results： Of these 21 patients, the best overall response was partial response （PR） in 6 patients （28.6%）, stable disease （SD） in I0 patients （47.6%）, and progressive disease （PD） in 5 patients （23.8%）. The overall response rate （ORR） was 28.6% and the disease control rate （DCR） （PR ＋ SD） was 76.2%. The median progression-flee survival （PFS） was 4.0 months （95% CI, 5.0-7.0 months）. The main grade 3/4 toxicities included neutropenia （11.1%）, peripheral nerve toxicity （5.6%）, muscle and joint aches （5.6%）, and fatigue （5.6%）. Conclusions： The ABP monotherapy can achieve good objective response in advanced NSCLC patients who have previously received multiple cycles of treatment and be well tolerated.
