3-Methyladenine potentiates paclitaxel-induced apoptosis and phosphorylation of cyclin-dependent kinase 1 at thr161 in nasopharyngeal carcinoma cell

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.

Paclitaxel induces human KOSC3 oral cancer cell apoptosis through caspase pathways

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.

Hemorrhagic cystitis in gastric cancer after nanoparticle albuminbound paclitaxel:A case report

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.

Ganoderma lucidum spore oil enhances the effect of paclitaxel,improves the tolerance to paclitaxel and prolongs the survival in Lewis tumor-bearing mice

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.

Pharmacokinetic study of paclitaxel in malignant ascites from advanced gastric cancer patients

AIM： To examine the paclitaxel concentrations in plasma and ascites after its intravenous administration in patients with ascites due to peritonitis carcinomatosa resulting from advanced gastric cancer. METHODS： Two patients with ascites due to peritonitis carcinomatosa resulting from gastric cancer were included in this study. The paclitaxel concentrations in plasma and ascites were investigated for 72 h in case 1 and 168 h in case 2 after intravenous administration. RESULTS： The paclitaxel concentration in plasma peaked immediately after administration, followed by rapid decrease below the threshold value of 0.1 μmol （85 ng/mL） within 24 h. In contrast, the paclitaxel concentration in ascites increased gradually for 24 h after administration to a level consistent with the level found in plasma. After 24 h the level of paclitaxel in ascites and plasma became similar, with the optimal level being maintained up to 72 h following administration. CONCLUSION： The concentration of paclitaxel in ascites is maintained within the optimal level for the treatment of cancer cells for up to 72 h after intravenous administration. Paclitaxel is a promising drug for the treatment of malignant ascites of gastric cancer.

Pharmacokinetics of paclitaxel in a hemodialysis patient with advanced gastric cancer: A case report

We report for the first time the possibility of weekly paclitaxel chemotherapy for a patient with advanced, nonresectable gastric cancer undergoing hemodialysis. A 50-year-old man with chronic renal failure due to bilateral polycystic kidneys, who had undergone hemodialysis three times a week for 5 years, presented with hematemesis in December 2004. Based on the diagnosis of gastric cancer with lymph node metastases, surgery was performed. On the 15th postoperative day, the patient was treated with chemotherapy using paclitaxel. Paclitaxel was administered at a dose of 60 mg/m^2 as a 1 h iv infusion in 250 mL of saline. Hemodialysis was started 1 h after the completion of the paclitaxel infusion and was performed for 3 h. Paclitaxel was administered weekly on d 1, 8, and 15 on a 28-d cycle. The maximum plasma concentration of paclitaxel was 1390 μg/L. The area under the curve of paclitaxel was 4398.6 μg·h/L. Grade 2 leukopenia was encountered during the first cycle. The plasma concentrations of paclitaxel from 6 to over 24 h after the infusion were 0.01 to 0.1 μmol/L in our patient, and these concentrations have been shown to be effective on inhibiting the growth of gastric cancer cells without producing adverse side effects in the patient. The plasma concentration of paclitaxel was not influenced by hemodialysis. We conclude that the pharmacokinetics of paclitaxel is not altered in a patient with renal failure, and that weekly paclitaxel is a suitable treatment regimen for hemodialysis patients with advanced gastric cancer.

STUDIES ON THE PHARMACODYNAMICS AND PHARMACOKINETICS OF PACLITAXEL(Zisu^R)

Pharmacological studies demonstrated that paclitaxel (Zisu() was very active in the inhibition of the growth of human cancer cell panel including KB cells, HCT-8, A2780, and MCF-7 cells. The IC50 was as low as 0.0019, 0.0019, 0.0036 and 0.01 ( g/ml respectively. Experimental therapeutic studies indicated that paclitaxel(Zisu() significantly inhibited the growth of melanoma B-16, Walker carcinomsarcoma and heterotransplanted human ovarian cancer in nude mice. Biochemical pharmacological studies showed that paclitaxel (Zisu() could accelerate microtubule assembly and inhibit its deassembly; population in G1 was decreased while the cell population in G2+M phase was increased significantly. In addition, a polyploid cell population appeared. Pharmacokinetic studies demonstrated that the t1/2( was 0.12 h and t1/2( was 5.02 h when it was injected intravenously at a dose of 5 mg/kg in rats. The AUC, Vc and CLs were 11.82(( g.h)/ml, 0.50L/kg and 0.42L(h.kg) respectively.

A rapid and sensitive determination of paclitaxel in rat plasma by UPLC-MS/MS method: Application to a pharmacokinetic study

A rapid and sensitive method for quantitative determination of paclitaxel in rat plasmawas developed and validated by using ultra-performance liquid chromatography-tandemmass spectrometry (UPLC-MS/MS). Docetaxel was used as an internal standard anddiethyl ether was the liquideliquid extraction agent. Multiple reaction monitoring (MRM)mode via positive electrospray ionization (ESI) was applied to detect paclitaxel and IS at thetransitions m/z 854 / 286 and m/z 808.48 / 527.3, respectively. This method covered alinearity range from 5 to 5000 ng/ml, with the total run time of 3.0 min. In summary, a highthroughout UPLC-MS/MS method was successfully developed to measure paclitaxel in ratplasma and was applied to pharmacokinetic study after intravenous administration ofpaclitaxel.

Comparing effectiveness and safety of paclitaxel plus raltitrexed vs. paclitaxel alone in second-line palliative chemotherapy for metastatic gastric adenocarcinoma: A randomized phase Ⅱ clinical trial

Objective:Paclitaxel(P)is a standard second-line chemotherapy in the treatment of advanced gastric cancer.This study compared the clinical outcome of a paclitaxel plus raltitrexed(RP)regimen as second-line treatment in metastatic gastric cancer(MGC)patients.Methods:An open,randomized,multi-center phase Ⅱ clinical trial was conducted involving 148 patients who were randomly assigned and treated with RP[raltitrexed(3 mg/m^(2)on day 1)and paclitaxel(135 mg/m^(2)on day 1 every 3 weeks)]or P[paclitaxel(135 mg/m^(2)on day 1 every 3 weeks)]as 2nd-line chemotherapy.The primary endpoint was progression-free survival(PFS).The secondary endpoints were the overall response rate(ORR),overall survival(OS),and safety.Results:PFS had a tendency to be prolonged with RP compared to P(2.7 months vs.1.7 months;P=0.148).OS was also prolonged with RP compared to P(10.2 months vs.6.1 months;P=0.140).The ORR was equal in the RP and P groups(6.8%and 4.0%;P=0.72).The disease control rate(DCR)in the RP and P groups was 56.2%and 36.0%,respectively.Grade 3-4 treatment-related adverse events occurred in 36.2%(RP)and 28.2%(P)of patients.Frequent grade 3-4 toxicities for RP and P were neutropenia(11.0%and 4.0%),anemia(1.4%and 4.0%),and thrombocytopenia(1.4%and 5.3%),and all grades of peripheral neurotoxicity(12.3%vs.17.3%).All grades of hepatic toxicity were demonstrated for the RP and P groups based on elevated aminotransferase levels(27.4%and 14.1%).Subgroup analysis shows if MGC was combined with ascites or peritoneal involvement,the OS of the RP regimen was longer(P=0.05).Conclusions:Second-line palliative chemotherapy with RP was shown to prolong the PFS and OS,especially among patients with ascites or peritoneal involvement,which warrants confirmation using larger sample studies.

The Combination of Artesunate and Paclitaxel in 1:1 Ratio Induces Apoptosis and Morphology Change on Human Prostate Cancer Cell Lines

The combination of Artesunate (ART) and Paclitaxel (PTX) in two human prostate cancer (PCa) cell lines (PC-3 and LNCaP) was evaluated to investigate the effects on proliferation, apoptosis and morphological changes. The half maximal inhibitory concentration (IC50) values that were observed by ART and PTX on both LNCaP and PC-3 cell lines at 72-and 120-hour exposure were used to assess these effects. Early and late apoptosis was detected in Annexin V-FITC/PI assay revealed a shift in population of cells towards early and mid-apoptosis with ART + PTX than with ART and PTX individually. More effects were observed on LNCaP cell lines at both 72-hour and 120-hour exposure. The results for the Caspase 3/7 activity assay showed shift of viable population in all induced samples compared to control. Morphological changes occurred in both cell lines;this was validated in qualitative assessment when examined under the inverted microscope. These findings indicated that ART + PTX suppressed PCa cell proliferation in a dose- and time-dependent manner.

Anti-tumor Effect of Paclitaxel Enhanced by Psoralen at the Cellular Level

[Objectives]To explore the effect of psoralen combined with paclitaxel on the apoptosis of MCF-7 cells.[Methods]The effects of different concentrations of psoralen,paclitaxel,or the combination of psoralen and paclitaxel on cell viability were detected using CCK-8 assay kit.Cell cycle distribution and apoptosis after 24 h of psoralen(0.16,0.32,0.64 mmol/L),paclitaxel(0.1μmol/L),combined action of psoralen(0.32 mmol/L)and paclitaxel(0.1μmol/L)were detected using flow cytometry.[Results]Lower concentration of psoralen(0.04-0.32 mmol/L)showed no significant inhibitory effect on cells.After combined with paclitaxel,the inhibitory effect on MCF-7 cell proliferation was significantly higher than that of the group treated alone.Compared with the paclitaxel group,the cell apoptosis rate in the drug combination group was significantly increased.Different low concentrations of psoralen can block the cell cycle of MCF-7 at G 0/G 1 phase,while paclitaxel can block the cell cycle at G 2/M phase.After combined action,the number of cells blocked at G 2/M phase decreased.[Conclusions]Overall,the combined effect of psoralen and paclitaxel can enhance anti-tumor ability by inhibiting cell proliferation,inducing apoptosis,and blocking cell cycle.

Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer

Background:Unresectable locally advanced or metastatic triple-negative(hormone-receptor-negative and human epidermal growth factor receptor 2[HER2]-negative)breast cancer is an aggressive disease with poor outcomes.Nanoparticle albumin-bound(nab)-paclitaxel may enhance the anticancer activity of atezolizumab.

白蛋白结合型紫杉醇或多西他赛联合卡铂新辅助治疗HER2阳性乳腺癌疗效比较

目的比较在真实世界临床实践中曲妥珠单抗和帕妥珠单抗(HP)分别配伍白蛋白结合型紫杉醇加卡铂方案与多西他赛加卡铂方案新辅助治疗HER2阳性乳腺癌的疗效。方法回顾性收集2019年6月至2021年12月在河北省共11家三级甲等医院接受HP分别配伍白蛋白结合型紫杉醇加卡铂方案与多西他赛加卡铂方案新辅助治疗并完成后续手术的HER2阳性乳腺癌患者的临床资料,比较两组患者的总体病理完全缓解(tpCR)率。结果共纳入76例患者,其中白蛋白结合型紫杉醇组47例,多西他赛组29例。白蛋白结合型紫杉醇组tpCR率显著高于多西他赛组(72.3%vs.48.3%,χ^(2)=4.463,P=0.035)。亚组分析表明,年龄大于40岁、cN2-3、cTNMⅢ期、激素受体(+)、Ki67>30%患者中,白蛋白结合型紫杉醇组tpCR率高于多西他赛组,差异有统计学意义(P<0.05)。结论在真实世界临床实践中,HP配伍白蛋白结合型紫杉醇加卡铂方案新辅助治疗HER2阳性乳腺癌的疗效优于HP配伍多西他赛加卡铂方案。

靶向FOLR1的脱氧核酶提高鼻咽癌移植瘤对紫杉醇的敏感性

目的:探讨裸鼠鼻咽癌移植瘤能否通过靶向FOLR1的脱氧核酶(DrzE)提高其对紫杉醇的敏感性。方法:取CNE-1鼻咽癌亲本细胞及CNE-1/taxol紫杉醇耐药细胞进行裸鼠成瘤实验,分别予靶向FOLR1的“10-23”型DrzE单用和紫杉醇单用及紫杉醇-DrzE联用后比较各组鼻咽癌移植瘤体的抑制情况。RT-qPCR及Western blot检测用药前后各组瘤体FOLR1 mRNA及蛋白的表达。结果:CNE-1瘤体较CNE-1/taxol瘤体生长速度快,瘤体体积更大(P<0.05);CNE-1瘤体生长能被紫杉醇单药抑制,但紫杉醇对CNE-1/taxol瘤体无效;两种瘤体生长均能被DrzE单药抑制,其中耐药瘤体更显著(P<0.05);紫杉醇与DrzE联用较分别单用两药对移植瘤的抑制作用更显著(P<0.05);给药前CNE-1/taxol移植瘤中FOLR1的表达量显著高于CNE-1(P<0.01),用药后DrzE单药组及紫杉醇与DrzE联用组中两种移植瘤体FOLR1表达量均显著低于对照组(P<0.05)。结论:靶向FOLR1的脱氧核酶DrzE转染裸鼠移植瘤体后可减慢鼻咽癌瘤体的生长,提高鼻咽癌耐药移植瘤体对紫杉醇的敏感性。

miR-152-3p表达下调降低紫杉醇耐药人卵巢癌细胞A2780T对紫杉醇的耐药性

目的探讨miR-152-3p对紫杉醇耐药人卵巢癌细胞A2780T对紫杉醇耐药性的影响及机制。方法①紫杉醇(1.875,3.75,7.5,17和23μmol·L^(-1))与人卵巢癌A2780和A2780T细胞作用48 h,MTT法检测细胞存活率,计算抑制细胞存活半数抑制浓度(IC50)值和耐药指数(RI)。Western印迹法检测A2780和A2780T细胞耐药蛋白P-糖蛋白(P-gp)、多药耐药相关蛋白1(MRP1)和三磷酸腺苷结合转运蛋白G超家族成员2(ABCG2)蛋白表达。②实时荧光定量PCR(RT-qPCR)检测A2780和A2780T细胞miR-152-3p表达水平。脂质体瞬时转染技术转染miR-152-3p抑制物降低A2780T细胞中miR-152-3p表达(miR-152-3p抑制物组),同时设转染miR-152-3p阴性对照组,RT-qPCR检测转染效率,MTT法、划痕实验和流式细胞术分别检测转染miR-152-3p抑制物对A2780T细胞存活、迁移和凋亡的影响;Western印迹法检测转染miR-152-3p抑制物对A2780T细胞Bax和Bcl-2蛋白表达的影响。③用miRDB,Targetscan,miRWalk和Starbase数据库预测miR-152-3p的靶基因,并用Western印迹法检测转染miR-152-3p抑制物后A2780T细胞磷酸酯酶张力蛋白同源物(PTEN)蛋白表达的变化及RT-qPCR检测A2780和A2780T细胞PTEN mRNA表达水平予以验证。随后,脂质体瞬时转染技术转染PTEN siRNA沉默A2780T细胞中PTEN表达,同时设转染siRNA阴性对照组,RT-qPCR检测转染效率,MTT法检测沉默PTEN表达后A2780T细胞存活率和IC50值,Western印迹法检测P-gp,MRP1和ABCG2蛋白表达。结果①紫杉醇处理后A2780和A2780T细胞存活率均降低(P<0.01),A2780T细胞RI为2.8。与A2780细胞相比,A2780T细胞P-gp,MRP1和ABCG2蛋白高表达(P<0.05,P<0.01)。②与A2780细胞相比,A2780T细胞miR-152-3p明显高表达(P<0.01)。与转染miR-152-3p阴性对照组比较,转染miR-152-3p抑制物后A2780T细胞存活率(P<0.05,P<0.01)和细胞迁移能力(P<0.05)明显降低,细胞凋亡率升高(P<0.01);Bax蛋白表达增加(P<0.01),Bcl-2蛋白表达降低(P<0.05)。③生物信息学数据库分析结果提示,PTEN是miR-152-3p的一个靶基因;Western印迹法验证显示,转染miR-152-3p抑制物组A2780T细胞PTEN蛋白表达低于转染miR-152-3p阴性对照组(P<0.05);RT-qPCR结果显示,A2780T细胞PTEN mRNA表达水平高于A2780细胞(P<0.01)。转染PTEN siRNA沉默PTEN表达后,与转染siRNA阴性对照组相比,A2780T细胞存活率(P<0.05,P<0.01)和IC50值(P<0.01)显著降低,P-gp,MRP1和ABCG2蛋白表达降低(P<0.05,P<0.01)。结论miR-152-3p在A2780T细胞中高表达,其表达下调可抑制A2780T细胞增殖和迁移,促进细胞凋亡,降低A2780T细胞对紫杉醇的耐药性,该作用可能是通过降低其靶基因PTEN表达发挥的。

表柔比星、紫杉醇化疗辅助胃癌根治术患者血清HSP90α、CYFR211水平变化及预后影响因素分析

目的分析表柔比星联合紫杉醇化疗的胃癌根治术患者血清HSP90α、CYFR211水平及预后影响因素。方法选择胃癌根治术的患者96例,均采用表柔比星联合紫杉醇经动脉介入化疗。比较治疗前、治疗6周后、治疗12周后患者血清HSP90α、CYFR211水平。对患者随访2年,统计患者无进展生存时间(PFS)和总生存时间(OS),根据实体肿瘤WHO客观评价标准对患者预后进行评估,分为预后不良组和预后良好组,并通过单因素分析和多因素logistic回归分析影响胃癌根治术患者预后的危险因素。结果治疗6周后,2组患者血清HSP90α、CYFR211水平较治疗前低(P<0.05),治疗12周后,2组患者血清HSP90α、CYFR211水平较治疗前及治疗6周后低(P<0.05)。患者6个月、1年、2年无进展生存率分别为58.3%、30.2%、20.2%,6个月、1年、2年总生存率分别为81.2%、63.5%、32.6%,中位PFS和OS分别为10个月、16个月。单因素分析显示:胃癌根治术患者的预后与性别、体质指数、手术出血量、手术方式、术后是否出现严重不良反应、胃癌发生部位无关(P>0.05),而与年龄、肿瘤直径、手术时间、胃切除范围、TNM分期、肿瘤分化程度有关(P<0.05);多因素分析显示,年龄、肿瘤直径、胃切除范围、手术时间、TNM分期、肿瘤分化程度是影响胃癌根治术患者预后不良的独立危险因素(P<0.05)。结论表柔比星联合紫杉醇经动脉介入化疗治疗胃癌根治术患者,可以降低血清HSP90α、CYFR211水平,疗效尚可。年龄、肿瘤直径、胃切除范围、手术时间、TNM分期、肿瘤分化程度是胃癌根治术患者预后的独立影响因素。

晚期宫颈癌患者行白蛋白结合型紫杉醇联合顺铂治疗前后的变化分析

目的 分析晚期宫颈癌患者行白蛋白结合型紫杉醇联合顺铂治疗前后的变化。方法 100例晚期宫颈癌患者,随机分为研究组和对照组,每组50例。两组患者均接受规定治疗方案同步放化疗,研究组使用注射用紫杉醇(白蛋白结合型)联合顺铂化疗治疗,对照组采用溶剂型紫杉醇联合顺铂化疗治疗。比较两组患者病情缓解程度、毒副反应发生情况(血红蛋白降低、血小板减少、白细胞减少、中性粒细胞减少、胃肠道反应、肝功能异常)、治疗前后肿瘤标志物指标[癌胚抗原(CEA)、鳞状细胞癌抗原(SCC-Ag)、细胞角蛋白19片段抗原(CYFRA21-1)、糖类抗原125(CA125)]水平、2年内病情恶化、生存情况。结果 研究组治疗后的病情总缓解率66.00%高于对照组的46.00%,差异有统计学意义(P<0.05)。研究组胃肠道反应发生率16.00%低于对照组的34.00%,差异有统计学意义(P<0.05)。治疗后,研究组患者CEA(8.05±1.19)U/ml、SCC-Ag(1.86±0.41)ng/ml、CYFRA21-1(8.11±1.52)ng/ml、CA125(26.32±2.86)U/ml均低于对照组的(8.86±1.38)U/ml、(2.13±0.49)ng/ml、(9.03±1.85)ng/ml、(27.64±3.13)U/ml,差异有统计学意义(P<0.05)。研究组治疗后2年内的病情恶化率46.00%低于对照组的66.00%,生存率82.00%高于对照组的64.00%,恶化时间(1.15±0.54)年、死亡时间(1.48±0.46)年均晚于对照组的(0.91±0.52)、(1.23±0.45)年,差异有统计学意义(P<0.05)。结论 给予晚期宫颈癌患者白蛋白结合型紫杉醇联合顺铂治疗可增加病灶缓解程度,减少胃肠道反应,降低治疗后短期内的病情恶化发生率,同时提高患者生存能力。

紫杉醇-天然冰片复合物亚微乳的制备与质量标准及初步活性研究

目的制备紫杉醇-天然冰片复合物,同时探究紫杉醇-天然冰片复合物亚微乳的处方和制备工艺及体外抗肿瘤效果。方法采用研磨法制备紫杉醇-天然冰片复合物并经红外光谱(FT-IR)和差式扫描量热(DSC)分析鉴定所得固体复合物;采用两步高压乳匀法制备复合物亚微乳,应用单因素考察和正交实验优化处方及制备工艺,通过噻唑蓝(MTT)比色法实验、细胞克隆形成实验、细胞划痕实验,考察该制剂对HCT-116细胞的作用效果。结果复合物中紫杉醇3312.76 cm^(-1)和3513.92 cm^(-1)的红外光谱吸收峰消失,且DSC分析显示在154.56℃处出现一个明显的新的吸收峰,表明紫杉醇可能与天然冰片偶联,形成新的复合物。复合亚微乳最佳处方为10%脂肪酸甘油酯,原料药0.44%[紫杉醇-天然冰片(1∶3)],3%混合乳化剂[蛋黄卵磷脂-泊洛沙姆188(1∶2)],2.0%甘油,0.3%油酸;最佳工艺为80℃乳化,60 MPa高压均质10次,再于100℃水浴灭菌45 min。细胞MTT实验中其半数抑制浓度(IC 50)为0.75μg·mL^(-1),细胞克隆实验结果中,空白对照组、紫杉醇原料药及紫杉醇-天然冰片亚微乳的划痕愈合面积分别为(36.44±3.35)%、(13.59±9.28)%、(8.30±4.09)%(P<0.05);平板克隆实验中,空白对照组,紫杉醇原料药组,亚微乳组细胞克隆率分别为(37.92±0.729)%、(9.16±1.335)%、(3.36±1.065)%(P<0.05)。结论紫杉醇-天然冰片亚微乳注射液处方及工艺合理,质量稳定。细胞实验表明,该亚微乳注射剂能明显抑制HCT-116细胞的增殖和迁移。

信迪利单抗注射液联合注射用紫杉醇(白蛋白结合型)治疗复发或难治性ES-SCLC的临床研究

目的:评估信迪利单抗注射液联合注射用紫杉醇(白蛋白结合型)在复发或难治性广泛期(ES)小细胞肺癌(SCLC)患者二线治疗中的疗效和安全性。方法:选择2022年1月至2023年1月首都医科大学附属北京友谊医院收治的一线应用依托泊苷/铂类药物化疗后进展的ES-SCLC患者74例,根据随机数字表法分为研究组38例和对照组36例。研究组患者给予信迪利单抗注射液联合注射用紫杉醇(白蛋白结合型)治疗,对照组患者给予注射用盐酸托泊替康治疗。观察两组患者的客观缓解率(ORR)、疾病控制率(DCR)、无进展生存期(PFS)、总生存期(OS)及不良反应。结果:研究组、对照组患者的ORR分别为26.3%(10/38)、13.9%(5/36)(P=0.035),DCR分别为84.2%(32/38)、72.2%(26/36)(P=0.042),中位PFS分别为6.00、3.45个月(P=0.013),中位OS分别为10.30、8.75个月(P=0.007),上述差异均有统计学意义。两组患者不良反应发生率的差异无统计学意义(P>0.05)。结论:与注射用盐酸托泊替康相比,信迪利单抗注射液联合紫杉醇(白蛋白结合型)延长了复发或难治性ES-SCLC患者的生存期,且不良反应可耐受。

基于肿瘤因子、炎症状态探究紫杉醇白蛋白辅助铂类化疗治疗复发转移性宫颈癌的疗效及安全性

目的:基于肿瘤因子、炎症状态探究紫杉醇白蛋白辅助铂类化疗治疗复发转移性宫颈癌的疗效及安全性。方法:选取2020年1月至2023年1月本院100例复发转移性宫颈癌患者,采用电脑随机数字表法随机分为两组,其中对照组50例,采用紫杉醇辅助奈达铂方案治疗,研究组50例,采用紫杉醇白蛋白辅助奈达铂方案治疗。比较两组近期疗效、肿瘤因子、炎症因子、复发转移相关指标、生存质量、功能状态、不良反应。结果:研究组总缓解率(72.00%)高于对照组(48.00%)(P<0.05);研究组治疗1个周期、3个周期后血清细胞角蛋白19片段抗原21-1(CYFRA21-1)、糖链抗原724(CA724)、鳞状细胞癌抗原(SCC-Ag)、白介素-4(IL-4)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平低于对照组,血清微小RNA-367(mi R-367)、微小RNA-383(miR-383)水平、肿瘤患者生活质量评分(QOL)、卡氏功能状态评分(KPS)评分高于对照组(P<0.05);研究组治疗期间恶心/呕吐、腹泻、疲倦、白细胞减少、过敏反应发生率与对照组比较,差异无统计学意义(P>0.05),但总不良反应发生率(12.00%)低于对照组(32.00%)(P<0.05)。结论:紫杉醇白蛋白辅助奈达铂在复发转移性宫颈癌治疗中疗效可靠,能进一步下调肿瘤因子水平,缓解炎症状态,且安全性较高。