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
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
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
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
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 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
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
BACKGROUND The advanced first-line regimen for advanced gastric cancer is based on a combination of fluoropyrimidine and platinum and/or paclitaxel(PTX),forming a two-or three-drug regimen.Compared to conventional PTX...BACKGROUND The advanced first-line regimen for advanced gastric cancer is based on a combination of fluoropyrimidine and platinum and/or paclitaxel(PTX),forming a two-or three-drug regimen.Compared to conventional PTX,nanoparticle albumin-bound PTX(Nab-PTX)has better therapeutic effects and fewer adverse effects reported in studies.Nab-PTX is a great option for patients presenting with advanced gastric cancer.Herein,we highlight an adverse event(hemorrhagic cystitis)of Nab-PTX in advanced gastric cancer.CASE SUMMARY A 55-year-old male was diagnosed with lymph node metastasis after a laparo-scopic-assisted radical gastrectomy for gastric cancer that was treated by Nab-PTX and S-1(AS).On the 15th day after treatment with AS,he was diagnosed with hemorrhagic cystitis.CONCLUSION Physicians should be aware that hemorrhagic cystitis is a potential adverse event associated with Nab-PTX treatment.展开更多
Background:The paclitaxel liposome formulation,encapsulating paclitaxel within a phospholipid bilayer,ad-dresses the insolubility of traditional paclitaxel formulations,thereby reducing toxicity without compromising i...Background:The paclitaxel liposome formulation,encapsulating paclitaxel within a phospholipid bilayer,ad-dresses the insolubility of traditional paclitaxel formulations,thereby reducing toxicity without compromising its antitumor efficacy.Methods:This multicenter,open-label,non-inferiority randomized controlled trial(ChiCTR2000038555)evalu-ates the efficacy and safety of paclitaxel liposome in comparison to the standard regimen of paclitaxel combined with carboplatin(PLC vs.PC)as first-line therapy in patients with epithelial ovarian cancer.Results:An analysis of median progression-free survival(PFS)revealed non-inferior outcomes between 263 pa-tients in the PLC group and 260 patients in the PC group(32.3 vs.29.9 months,hazard ratio[HR],0.89[95%CI,0.64−1.25]),using a non-inferior margin of 1.3.Although the overall incidence of treatment-related adverse events was comparable between groups,the PLC group experienced significantly fewer non-hematologic toxicities than those treated with the PC regimen.Conclusion:The findings affirm the non-inferiority of paclitaxel liposome compared to the combination of pa-clitaxel and carboplatin regarding therapeutic efficacy,with an enhanced safety profile marked by reduced non-hematologic toxicities.展开更多
Paclitaxel(PTX)is widely applied for the treatment of unresectable and metastasis breast carcinoma as well as other cancers,whereas its efficacy is always impeded by poor solubility.Liposomes are one kind of the most ...Paclitaxel(PTX)is widely applied for the treatment of unresectable and metastasis breast carcinoma as well as other cancers,whereas its efficacy is always impeded by poor solubility.Liposomes are one kind of the most successful drug carriers which are capable of solubilizing PTX and improving patients’tolerance owing to excellent biocompatibility and biodegradability.However,poor compatibility between PTX and liposomes compromises the stability,drug loading and anti-tumor capacity of liposomal formulations.To address this issue,three lipids with various chain lengths,namely,myristic acid(MA,14C),palmitic acid(PA,16C)and stearic acid(SA,18C),were conjugated to PTX via ester bonds and the synthesized prodrugs with high lipophilicity were further formulated into liposomes,respectively.All liposomes show high stability and drug loadings,as well as sustained drug release.The chain lengths of lipids are negatively correlated with drug release and enzymatic conversion rates,which further impact the pharmacokinetics,tumor accumulation,and anti-tumor efficacy of liposomal PTX.Neither rapid nor slow drug release facilitates high tumor accumulation as well as anti-tumor efficacy of PTX.Among all liposomes,PTX-PA-loaded liposomes show the longest circulation and highest tumor accumulation of PTX and exert the most potent anti-tumor capacities in vivo,owing to its moderate drug release and enzymatic conversion rate.Witnessing its superior safety,PTX-PA liposomes hold potential for further clinical translation.展开更多
Paclitaxel,a tetracyclic diterpenoid,has garnered attention for its potent anti-cancer properties and intricate molecular structure,making it a significant target for chemical synthesis and biosynthesis[1].However,its...Paclitaxel,a tetracyclic diterpenoid,has garnered attention for its potent anti-cancer properties and intricate molecular structure,making it a significant target for chemical synthesis and biosynthesis[1].However,its natural sources are extremely limited,as it is derived exclusively from the bark of endangered genus Taxus plants,which contain paclitaxel in very low concentrations(0.01%−0.05%)[2-3].Recent advances in synthetic biology present promising opportunities to enhance paclitaxel levels in Taxus cell cultures or to enable the reconstitution of its production in heterologous hosts,such as yeast or tobacco(Nicotiana benthamiana).展开更多
Background:Nasopharyngeal carcinoma(NPC)exhibits a significant prevalence in the southern regions of China,and paclitaxel(PTX)is frequently employed as a medication for managing advanced NPC.However,drug resistance is...Background:Nasopharyngeal carcinoma(NPC)exhibits a significant prevalence in the southern regions of China,and paclitaxel(PTX)is frequently employed as a medication for managing advanced NPC.However,drug resistance is typically accompanied by a poor prognosis.Exploring the synergistic potential of combining multiple chemotherapeutic agents may represent a promising avenue for optimizing treatment efficacy.Methods:This study investigated whether 3-Methyladenine(3-MA)could potentiated the effect of PTX and its potential molecular mechanism.Samples were divided into the following categories:Negative control(NC)with the solvent dimethyl sulfoxide(DMSO,0.5%v/v),PTX(400 nM),3-MA(4 mM),and PTX(400 nM)+3-MA(4 mM).The viability of NPC cells was assessed using both the cell counting kit-8(CCK-8)assay and the colony formation assay.Microscopic observation was performed to identify morphological cell changes.Flow cytometry was used to assess cell cycle status,mitochondrial membrane potential(MMP),and apoptotic cells.Western blotting was conducted to quantify the protein expression.Results:3-MA enhanced PTX-specific inhibition of NPC cell proliferation.PTX,either alone or in combination with 3-MA,caused cell cycle halt at the G2/M phase in the majority of NPC cells,and the combination treatment of PTX with 3-MA induced a higher rate of NPC cell death compared to PTX alone.Western blotting results revealed the combination of PTX with 3-MA heightened activation of cyclin-dependent kinase 1(CDK1),a key molecule in shifting cells from mitotic arrest to apoptosis,led to a reduction in Myeloid Cell Leukemia 1(MCL-1)expression and an increase in Poly(ADP-ribose)polymerase(PARP)cleavage.Conclusion:The concurrent administration of PTX with 3-MA effectively enhances PTX’s inhibitory impact on NPC and activates the apoptosis signal regulated by CDK1.展开更多
Background:Paclitaxel is a compound derived from Pacific yew bark that induces various cancer cell apoptosis.However,whether it also has anticancer activities in KOSC3 cells,an oral cancer cell line,is unclear.Methods:...Background:Paclitaxel is a compound derived from Pacific yew bark that induces various cancer cell apoptosis.However,whether it also has anticancer activities in KOSC3 cells,an oral cancer cell line,is unclear.Methods:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,flow cytometry,and western blotting assays were carried out to assess cell viability,subG1 phase of the cell cycle,and apoptosis-related protein expression,respectively.Results:Ourfindings indicate that paclitaxel could inhibit cell viability and increase the expression of apoptotic markers,including plasma membrane blebbing and the cleavage of poly ADP-ribose polymerase in KOSC3 cells.Also,the treatment with paclitaxel remarkably elevated the percentage of the subG1 phase in KOSC3 cells.In addition,treatment with a pan-caspase inhibitor could recover paclitaxel-inhibited cell viability.Moreover,caspase-8,caspase-9,caspase-7,and BH3 interacting domain death agonist(Bid)were activated in paclitaxel-treated KOSC3 cells.Conclusions:Paclitaxel induced apoptosis through caspase cascade in KOSC3 cells.展开更多
Purpose:This study aims to investigate whether Ganoderma lucidum spore oil(GLSO)could enhance the effect of paclitaxel(PTX),improve the tolerance to PTX and prolong the overall survival of Lewis tumor-bearing mice,whi...Purpose:This study aims to investigate whether Ganoderma lucidum spore oil(GLSO)could enhance the effect of paclitaxel(PTX),improve the tolerance to PTX and prolong the overall survival of Lewis tumor-bearing mice,which has never been reported before.Methods:The tumor,spleen,and thymus were weighed at the end of the experiment.Whole blood was collected for hematological index analysis,and the intact femur was removed to determine the bone marrow nucleated cell count(BMN).The percentage of lymphocytes in the spleen of mice was detected by flow cytometry,the activity of NK cells was detected by LDH assay,and the proliferation index of lymphocytes was determined by CCK-8 assay.The overall and mean survival time and life extension rate were calculated using SPSS software.Results:Our data showed that GLSO could enhance the anti-tumor effect of PTX and prolong the survival of mice.The underlying mechanisms of the above effects might be related to the toxic reduction effect of GLSO by relieving hematotoxicity,myelosuppression and immunosuppression.Specifically,GLSO could increase the number of blood cells and bone marrow cells,alleviate the thymic index,and elevate the number and activity of NK cells in mice treated with PTX.Conclusion:GLSO may enhance the efficacy of PTX by boosting the activity of immune NK cells and prolong survival by counteracting PTX-induced bone marrow alterations and improving hematopoiesis.These findings suggested the promising role of GLSO in combination with PTX to extend the survival and increase the tolerance of patients in clinical chemotherapy of lung cancer.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
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.
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 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.
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 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 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.
文摘BACKGROUND The advanced first-line regimen for advanced gastric cancer is based on a combination of fluoropyrimidine and platinum and/or paclitaxel(PTX),forming a two-or three-drug regimen.Compared to conventional PTX,nanoparticle albumin-bound PTX(Nab-PTX)has better therapeutic effects and fewer adverse effects reported in studies.Nab-PTX is a great option for patients presenting with advanced gastric cancer.Herein,we highlight an adverse event(hemorrhagic cystitis)of Nab-PTX in advanced gastric cancer.CASE SUMMARY A 55-year-old male was diagnosed with lymph node metastasis after a laparo-scopic-assisted radical gastrectomy for gastric cancer that was treated by Nab-PTX and S-1(AS).On the 15th day after treatment with AS,he was diagnosed with hemorrhagic cystitis.CONCLUSION Physicians should be aware that hemorrhagic cystitis is a potential adverse event associated with Nab-PTX treatment.
基金funded by the Optimization Study of Treatment Regimen and Clinical Practice in Ovarian Cancer(grant number:2016YFC1303702).
文摘Background:The paclitaxel liposome formulation,encapsulating paclitaxel within a phospholipid bilayer,ad-dresses the insolubility of traditional paclitaxel formulations,thereby reducing toxicity without compromising its antitumor efficacy.Methods:This multicenter,open-label,non-inferiority randomized controlled trial(ChiCTR2000038555)evalu-ates the efficacy and safety of paclitaxel liposome in comparison to the standard regimen of paclitaxel combined with carboplatin(PLC vs.PC)as first-line therapy in patients with epithelial ovarian cancer.Results:An analysis of median progression-free survival(PFS)revealed non-inferior outcomes between 263 pa-tients in the PLC group and 260 patients in the PC group(32.3 vs.29.9 months,hazard ratio[HR],0.89[95%CI,0.64−1.25]),using a non-inferior margin of 1.3.Although the overall incidence of treatment-related adverse events was comparable between groups,the PLC group experienced significantly fewer non-hematologic toxicities than those treated with the PC regimen.Conclusion:The findings affirm the non-inferiority of paclitaxel liposome compared to the combination of pa-clitaxel and carboplatin regarding therapeutic efficacy,with an enhanced safety profile marked by reduced non-hematologic toxicities.
基金supported by National Natural Science Foundation of China(Nos.82273867,82030107)Shanghai Science and Technology Project of Little Giant(No.1902HX76600)+1 种基金Shanghai Qingpu District Industry-University-Research Cooperative Development Funding Project(No.2022-7)High-level Talents of Fujian University of Chinese Medicine(No.X2019006-Talents).
文摘Paclitaxel(PTX)is widely applied for the treatment of unresectable and metastasis breast carcinoma as well as other cancers,whereas its efficacy is always impeded by poor solubility.Liposomes are one kind of the most successful drug carriers which are capable of solubilizing PTX and improving patients’tolerance owing to excellent biocompatibility and biodegradability.However,poor compatibility between PTX and liposomes compromises the stability,drug loading and anti-tumor capacity of liposomal formulations.To address this issue,three lipids with various chain lengths,namely,myristic acid(MA,14C),palmitic acid(PA,16C)and stearic acid(SA,18C),were conjugated to PTX via ester bonds and the synthesized prodrugs with high lipophilicity were further formulated into liposomes,respectively.All liposomes show high stability and drug loadings,as well as sustained drug release.The chain lengths of lipids are negatively correlated with drug release and enzymatic conversion rates,which further impact the pharmacokinetics,tumor accumulation,and anti-tumor efficacy of liposomal PTX.Neither rapid nor slow drug release facilitates high tumor accumulation as well as anti-tumor efficacy of PTX.Among all liposomes,PTX-PA-loaded liposomes show the longest circulation and highest tumor accumulation of PTX and exert the most potent anti-tumor capacities in vivo,owing to its moderate drug release and enzymatic conversion rate.Witnessing its superior safety,PTX-PA liposomes hold potential for further clinical translation.
文摘Paclitaxel,a tetracyclic diterpenoid,has garnered attention for its potent anti-cancer properties and intricate molecular structure,making it a significant target for chemical synthesis and biosynthesis[1].However,its natural sources are extremely limited,as it is derived exclusively from the bark of endangered genus Taxus plants,which contain paclitaxel in very low concentrations(0.01%−0.05%)[2-3].Recent advances in synthetic biology present promising opportunities to enhance paclitaxel levels in Taxus cell cultures or to enable the reconstitution of its production in heterologous hosts,such as yeast or tobacco(Nicotiana benthamiana).
基金supported by the Science and Technology Innovation Program of Hunan Province(Grant Numbers:2021SK1014 and 2022WZ1027)the Colleges and Universities of Hunan Province(Grant Number:HNJG 20200440)+1 种基金the Scientific Research Fund of Hunan Provincial Education Department(Grant Number:21B0411)the Scientific Research Project of Changsha Central Hospital(Number:YNKY202201).
文摘Background:Nasopharyngeal carcinoma(NPC)exhibits a significant prevalence in the southern regions of China,and paclitaxel(PTX)is frequently employed as a medication for managing advanced NPC.However,drug resistance is typically accompanied by a poor prognosis.Exploring the synergistic potential of combining multiple chemotherapeutic agents may represent a promising avenue for optimizing treatment efficacy.Methods:This study investigated whether 3-Methyladenine(3-MA)could potentiated the effect of PTX and its potential molecular mechanism.Samples were divided into the following categories:Negative control(NC)with the solvent dimethyl sulfoxide(DMSO,0.5%v/v),PTX(400 nM),3-MA(4 mM),and PTX(400 nM)+3-MA(4 mM).The viability of NPC cells was assessed using both the cell counting kit-8(CCK-8)assay and the colony formation assay.Microscopic observation was performed to identify morphological cell changes.Flow cytometry was used to assess cell cycle status,mitochondrial membrane potential(MMP),and apoptotic cells.Western blotting was conducted to quantify the protein expression.Results:3-MA enhanced PTX-specific inhibition of NPC cell proliferation.PTX,either alone or in combination with 3-MA,caused cell cycle halt at the G2/M phase in the majority of NPC cells,and the combination treatment of PTX with 3-MA induced a higher rate of NPC cell death compared to PTX alone.Western blotting results revealed the combination of PTX with 3-MA heightened activation of cyclin-dependent kinase 1(CDK1),a key molecule in shifting cells from mitotic arrest to apoptosis,led to a reduction in Myeloid Cell Leukemia 1(MCL-1)expression and an increase in Poly(ADP-ribose)polymerase(PARP)cleavage.Conclusion:The concurrent administration of PTX with 3-MA effectively enhances PTX’s inhibitory impact on NPC and activates the apoptosis signal regulated by CDK1.
基金The present study was supported by the National Science and Technology Council,Taiwan(MOST-107-2320-B-471-001 to YYL and MOST-110-2320-B-006-025-MY3 to BMH)by An Nan Hospital(ANHRF111-55 to TCC and BMH).
文摘Background:Paclitaxel is a compound derived from Pacific yew bark that induces various cancer cell apoptosis.However,whether it also has anticancer activities in KOSC3 cells,an oral cancer cell line,is unclear.Methods:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,flow cytometry,and western blotting assays were carried out to assess cell viability,subG1 phase of the cell cycle,and apoptosis-related protein expression,respectively.Results:Ourfindings indicate that paclitaxel could inhibit cell viability and increase the expression of apoptotic markers,including plasma membrane blebbing and the cleavage of poly ADP-ribose polymerase in KOSC3 cells.Also,the treatment with paclitaxel remarkably elevated the percentage of the subG1 phase in KOSC3 cells.In addition,treatment with a pan-caspase inhibitor could recover paclitaxel-inhibited cell viability.Moreover,caspase-8,caspase-9,caspase-7,and BH3 interacting domain death agonist(Bid)were activated in paclitaxel-treated KOSC3 cells.Conclusions:Paclitaxel induced apoptosis through caspase cascade in KOSC3 cells.
基金Authors of this research are in deep gratitude toward Professor Qin Wang from the Nanchang Research Institute,Sun Yat-sen University for her dedicated guidance and support to this work.This work was supported by the National Key R&D Program of China(2022YFC3500302)the Ministry of Science and Technology of China(No.2017YFC1703104)+1 种基金the Key Laboratory Project of Pharmaceutical Lipids in Guangdong Province(No.2020B1212070024)the Guangdong Province Key Areas R&D Program Project(No.2020B1111120002).
文摘Purpose:This study aims to investigate whether Ganoderma lucidum spore oil(GLSO)could enhance the effect of paclitaxel(PTX),improve the tolerance to PTX and prolong the overall survival of Lewis tumor-bearing mice,which has never been reported before.Methods:The tumor,spleen,and thymus were weighed at the end of the experiment.Whole blood was collected for hematological index analysis,and the intact femur was removed to determine the bone marrow nucleated cell count(BMN).The percentage of lymphocytes in the spleen of mice was detected by flow cytometry,the activity of NK cells was detected by LDH assay,and the proliferation index of lymphocytes was determined by CCK-8 assay.The overall and mean survival time and life extension rate were calculated using SPSS software.Results:Our data showed that GLSO could enhance the anti-tumor effect of PTX and prolong the survival of mice.The underlying mechanisms of the above effects might be related to the toxic reduction effect of GLSO by relieving hematotoxicity,myelosuppression and immunosuppression.Specifically,GLSO could increase the number of blood cells and bone marrow cells,alleviate the thymic index,and elevate the number and activity of NK cells in mice treated with PTX.Conclusion:GLSO may enhance the efficacy of PTX by boosting the activity of immune NK cells and prolong survival by counteracting PTX-induced bone marrow alterations and improving hematopoiesis.These findings suggested the promising role of GLSO in combination with PTX to extend the survival and increase the tolerance of patients in clinical chemotherapy of lung cancer.
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.
