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.

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.

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.

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.

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.

Efficacy and safety of albumin-bound paclitaxel in treating recurrent advanced non-small-cell lung cancer

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.

DL1106与doxorubicin和paclitaxel协同作用及其机制研究

目的探讨DL1106与doxorubicin和paclitaxel对三阴性乳腺癌细胞协同作用效果及研究机制。方法将三阴性乳腺癌细胞MDA-MB-231和BT549分为4组,对照组,DL1106,DL1106+doxorubicin,DL1106+paclitaxel组作用24和48 h。用流式细胞仪检测细胞凋亡率和细胞周期;用JC-1检测细胞膜电位;用Caspase-Glo?3/7 assay检测细胞内胱天蛋白酶活性;用Western blotting检测细胞周期、细胞凋亡相关蛋白表达。采用si RNA技术敲低P53和PUMA的表达后检测药物联合对细胞的作用效果。结果与DL1106单独作用组细胞相比,DL1106与doxorubicin和paclitaxel联合作用组的细胞在48 h后凋亡率显著下降。DL1106与doxorubicin和paclitaxel联合作用导致细胞膜电位大幅下降并使细胞内胱天蛋白酶活性显著升高。同对照组相比,DL1106,DL1106+doxorubicin,DL1106+paclitaxel作用组的细胞均抑制MDM2的表达,促进P53和PUMA的表达。DL1106+doxorubicin,DL1106+paclitaxel协同作用抑制细胞Cyclin D1和Bcl-2的表达,促进BAX的表达。用P53si RNA和PUMA si RNA分别敲低细胞P53和PUMA的表达后,发现DL1106+doxorubicin,DL1106+paclitaxel联合作用效果明显减弱。结论 DL1106与doxorubicin和paclitaxel对三阴性乳腺癌细胞均具有协同作用,且这种协同作用通过P53/PUMA/BAX/caspase途径发挥作用。

紫杉醇(Paclitaxel)治疗晚期鼻咽癌的临床研究

评价紫杉醇对晚期鼻咽癌的客观疗效及毒副反应。方法 :采用紫杉醇175mg/m2,3h静脉滴注 (每3周1次 )方案共治疗晚期鼻咽癌病人22例 ,所有病人均接受两个疗程以上的化疗。结果 :22例病人均可评价疗效 ,有7例病人达到PR ,有效率为31 .82 %。主要毒副反应为骨髓抑制、恶心和呕吐、肌痛和关节痛、脱发等。大部分病人为Ⅰ～Ⅱ度反应 ,病人耐受良好。经常规预防用药后 ,未观察到有严重的过敏反应。结论 :紫杉醇是一种对晚期鼻咽癌有效的化疗药物 ,该剂量的紫杉醇临床使用较为安全 ,值得进一步的临床研究。

A phase Ⅱ study of paclitaxel and nedaplatin as front-line chemotherapy in Chinese patients with metastatic esophageal squamous cell carcinoma

AIM:To evaluate the efficacy and safety of paclitaxelnedaplatin combination as a front-line regimen in Chinese patients with metastatic esophageal squamous cell carcinoma(ESCC).METHODS:A two-center,open-label,single-arm phaseⅡstudy was designed.Thirty-nine patients were enrolled and included in the intention-to-treat analysis of efficacy and adverse events.Patients received 175mg/m2of paclitaxel over a 3 h infusion on 1 d,followed by nedaplatin 80 mg/m2in a 1 h infusion on 2 d every3 wk until the documented disease progression,unac-ceptable toxicity or patient’s refusal.RESULTS:Of the 36 patients assessable for efficacy,there were 2 patients(5.1%)with complete response and 16 patients(41.0%)with partial response,giving an overall response rate of 46.1%.The median progression-free survival and median overall survival for all patients were 7.1 mo(95%CI:4.6-9.7)and 12.4 mo(95%CI:9.5-15.3),respectively.Toxicities were moderate and manageable.Grade 3/4 toxicities included neutropenia(15.4%),nausea(10.3%),anemia(7.7%),thrombocytopenia(5.1%),vomiting(5.1%)and neutropenia fever(2.6%).CONCLUSION:The combination of paclitaxel and nedaplatin is active and well tolerated as a first-line therapy for patients with metastatic ESCC.

Paclitaxel ameliorates fibrosis in hepatic stellate cells via inhibition of TGF-β/Smad activity

AIM: To investigated if paclitaxel can attenuate hepatic fi brosis in rat hepatic stellate cells (RHSCs). METHODS: RHSCs were cultured in vitro and randomly assigned to four groups: normal control group (treated only with Dulbecco's Modified Eagle's Medium), Taxol group (200 nmol/L paclitaxel was added to the cell culture), transforming growth factor (TGF)-β group (5 ng/mL recombinant human TGF-β1 was added to the cell culture), and TGF-β + Taxol group. TGF-β signaling cascade and status of various extracellular matrix proteins were evaluated by real time reverse transcriptase polymerase chain reaction and Western blotting. RESULTS: The paclitaxel treatment markedly suppressed Smad2/3 phosphorylation. This was associated with attenuated expression of collagen Ⅰ and Ⅲ and fi bronectin in RHSCs.CONCLUSION: These data indicate that 200 nmol/L paclitaxel ameliorates hepatic fi brosis via modulating TGF-β signaling, and that paclitaxel may have some therapeutic value in humans with hepatic fi brosis.

Adjuvant chemotherapy with paclitaxel and cisplatin in lymph node-positive thoracic esophageal squamous cell carcinoma

Objective： No standard postoperative adjuvant chemotherapy has ever been established in node-positive esophageal squamous cell carcinoma （ESCC）. This is a study to explore the effect of postoperative paelitaxel （PTX） and cisplatin （DDP） in lymph node-positive, completely resected thoracic ESCC patients. Methods： We conducted a prospective phase II trial. Patients had pathologically node-positive thoracic ESCC with negative margins. Outcomes of disease-free survival （DFS） and overall survival （OS） were compared with a matched historical control cohort. The postoperative chemotherapy regimen consisted of 4 to 6 cycles of PTX 150 mg/m2 administered intravenously on d 1 followed by DDP 50 mg/m2 on d 2 every 14 d. Results： Forty-three patients were accrued from December 2007 to May 2012 at Cancer Hospital of Chinese Academy of Medical Sciences for adjuvant chemotherapy. The historical control group consisted of 80 patients who received complete resection but no adjuvant chemotherapy during the same period of time. Of the 43 patients with adjuvant chemotherapy, 37 （86.0%） patients completed 4 to 6 cycles of chemotherapy. The 3-year DFS rates were 56.3% in the adjuvant group and 34.6% in the control group （P=0.006）. The 3-year OS rates were 55.0% in the adjuvant group and 37.5% in the control group （P=0.013）. Multivariate analysis revealed that postoperative chemotherapy was the significant predictor for improved OS （P=0.005）. Conclusions： Biweekly adjuvant PTX and DDP might improve 3-year DFS and OS in lymph node-positive, curatively resected thoracic ESCC patients. These conclusions warrant further study in randomized phase III clinical trials.

Expressions of Thymidylate Synthase, Thymidine Phosphorylase, Class Ⅲ β-tubulin, and Excision Repair Cross-complementing Group 1 Predict Response in Advanced Gastric Cancer Patients Receiving Capecitabine Plus Paclitaxel or Cisplatin

Objective: To evaluate the role of class III β-tubulin (TUBB3), thymidylate synthase (TS), thymidine phosphorylase (TP), and excision repair cross-complementing group 1 (ERCC1) in clinical outcome of advanced gastric cancer patients receiving capecitabine plus paclitaxel or cisplatin. Methods: The clinical data and tumor specimens from 57 advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel (cohort 1, n=36) and capecitabine plus cisplatin (cohort 2, n=21) were retrospectively collected, and TUBB3, TS, TP, and ERCC1 expressions were detected by real-time quantitative PCR. The associations between expressions of biomarkers and response or survival were analyzed statistically. Results: The median age of 57 patients was 57 years (range: 27–75 years) with 38 males and 19 females. Of all patients, the response rates of patients with high TP, low TP and high TS, low TS expressions were 57.1%, 27.6% (P=0.024), and 55.2%, 28.6% (P=0.042), respectively. Among cohort 1, the response rates and median overall survivals of patients with low and high TUBB3 expressions were 61.1% vs. 33.3% (P=0.095) and 13.8 months vs. 6.6 months (P=0.019), respectively; the response rate (87.5%) of patients with low TUBB3 and high TP expressions was higher than that (14.3%) of patients with high TUBB3 and low TP expressions (P=0.01). Among cohort 2, the response rates of patients with low ERCC1 and high ERCC1 expressions were 45.5% and 20.0% respectively (P=0.361). Conclusion: TUBB3, TS and TP expressions could predict the response of advanced gastric cancer patients receiving capecitabine-based and paclitaxel-based chemotherapy. These results will be further confirmed in future large samples.

Weekly albumin-bound paclitaxel/cisplatin versus gemcitabine/cisplatin as first-line therapy for patients with advanced non-small-cell lung cancer:A phase II open-label clinical study

Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advanced non-small-cell lung cancer(NSCLC).Methods: A total of 84 participants received either 100 mg/m^2 nab-paclitaxel each week on d 1, 8 and 15 of a 28 day cycle, as well as cisplatin 75 mg/m^2 on d 1 every three weeks(nab-TP arm); or gemcitabine 1,000 mg/m^2 on d 1 and 8, plus cisplatin 75 mg/m^2 on d 1 every three weeks(GP arm). The primary end point was progression-free survival(PFS). The secondary end points were overall response rate(ORR) and overall survival(OS).Results: According to our analysis, the median PFS was 4.8 months for the nab-TP arm vs. 5.2 months for the GP arm(P=0.55). Analysis showed the median OS was 14.6 months for participants who were in the nab-TP arm vs. 15.1 months for those in the GP arm(P=0.94). Besides, nab-TP showed OS advantages over GP in patients harboring epidermal growth factor receptor(EGFR) mutation(26.7 vs. 15.3 months, P=0.046) and patients with a performance status of 0(23.5 vs. 14.7 months, P=0.020). It was found that incidences of drug-related grade 3 or 4 toxicities were comparable between the two treatment arms.Conclusions: Therefore, it can be seen that weekly nab-TP treatment has a similar efficacy and tolerability to GP treatment for patients who are undergoing their first-line treatment for NSCLC. It could be that survival differences among platinum doublets in the context of both EGFR mutation and performance status have the potential to be the basis for our further clinical trials.

紫杉醇(Paclitaxel,紫素)治疗恶性肿瘤Ⅲ期临床研究报告

为了对紫杉醇的临床应用价值和药物不良反应进行进一步评价，根据协作组共同制定的Ⅲ期临床试用计划通过前瞻性多中心１６单位进行临床研究。共收治２４３例恶性肿瘤患者，均为有病理或细胞学证实的中晚期病人。单药治疗：所选病人大多为一般状况较好，首次治疗的晚期患者。应用紫杉醇１５０～１７５理学ｍｇ·ｍ－２，静脉滴注，３～５ｈ，每３～４周一次，２～３周期为一疗程。联合化疗主要为经手术、化疗、放疗后的晚期患者，所用方案为：紫杉醇静脉滴注１３５ｍｇ·ｍ－２，卵巢癌加顺铂８０ｍｇ·ｍ－２；乳腺癌加阿霉素４０ｍｇ·ｍ－２；肺癌加顺铂８０ｍｇ·ｍ－２或静脉滴注卡铂３５０ｍｇ·ｍ－２；食管癌加静脉滴注顺铂８０ｍｇ·ｍ－２，第１周和平阳霉素８ｍｇ，肌注２周，第１、２周使用。均每３周重复一次，２～３周期为一个疗程。结果本组可统计近期疗效的１９０例，治后完全缓解１４例，部分缓解７３例，无变化７７例，进展２６例，总有效率为４５．８％。卵巢癌单药治疗的有效比为３／４，与顺铂联合应用的有效率为３０％（６／２０）；乳腺癌单药治疗为６２．５％（１０／１６），与阿霉素联合应用为６０．０（２４／４０）；食管癌单用有效比为４／５，与顺铂及平阳霉素联合应用为?

Combination chemotherapy with paclitaxel,cisplatin and fluorouracil for patients with advanced and metastatic gastric or esophagogastric junction adenocarcinoma:a multicenter prospective study

Objective： To evaluate the efficacy and toxicity of the combination regimen of paclitaxel, cisplatin and 5-FU （PCF） as first-line or second-line therapy in patients with advanced gastric and esophagogastric junction （EGJ） adenocarcinoma in China. Methods： The patients were treated with paclitaxel 150 mg/m2 on dl; fractionated cisplatin 15 mg/m2 and continuous infusion 5-FU 600 mg/（mLd） intravenously on d 1-d5 of a 21-d cycle until disease progression or unacceptable toxicities. Results： Seventy-five patients have been enrolled, among which, 41 received PCF regimen as the first-line therapy （group A） and 34 received the regimen as the second-line therapy （group B） with the median age of 59 years old and Karnofsky performance status （KPS） score 〉80. Toxicities were analyzed in all 75 patients. Seventy-one patients were evaluable for efficacy. The median overall survival （mOS） was 12.0 months （95% CI： 7.9-16.2 months） in group A and 7.3 months （95% CI： 4.3-10.3 months） in group B, respectively. The median progression-free survival （mPFS） was 5.7 months （95% CI： 4.1-7.2 months） and 5.0 months （95% CI： 3.1-6.9 months）, respectively. The response rate （CR^PR） was 40% （16/40; 95% CI： 24.9-56.7%） in group A and 22.6% （7/31; 95% CI： 9.6-41.1%） in group B. Major grade 3 or 4 adverse events include neutropenia （41.3 %）, febrile neutropenia （9.3 %）, nausea/anorexia （10.7%）, and vomiting （5.3 %）. There was no treatment-related death. Conclusions： The combination chemotherapy with PCF is active and tolerable as first-line and second- line therapy in Chinese patients with advanced gastric and EGJ adenocarcinoma. The response and survival of PCF are same as those of DCF, but the tolerance is much better.

A phaseⅠtrial of an oral subtype-selective histone deacetylase inhibitor,chidamide,in combination with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer

Objective： This phase I study was to evaluate safety, maximum tolerated dose, pharmacokinetics and preliminary antitumor activity of chidamide, a novel subtype-selective histone deacetylase （HDAC） inhibitor, in combination with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer （NSCLC）. Methods： Ten patients received oral chidamide 20, 25, or 30 mg twice per week continuously with paclitaxel （175 mg/m2） and carboplatin [area under the curve （AUC） 5 mg/mL/min] administered in a 3-week cycle. Patients with response and stable disease after four cycles maintained chidamide monotherapy until disease progression or unacceptable toxicity. Blood samples were collected for pharmacoldnetic analysis after the first single oral of chidamide and first combination treatment in cycle 1 from all patients. Results： Two dose-limiting toxicities were recorded in the 30 mg cohort, including thrombocytopenia and prolonged neutropenia in the first cycle. Grade 3/4 neutropenia in any cycle was observed in all patients, but was not associated with significant complications. Other grade 3/4 hematologic toxicities included thrombocytopenia and leucopenia. No significant changes were observed in pharmacokinetic parameters for both chidamide and paclitaxel. One patient in the 20 mg cohort had confirmed partial response （PR）. Two out of 5 patients with brain metastases had intracranial complete remission after 4-cycle treatment. Conclusions： Chidamide combined with paclitaxel and carboplatin was generally tolerated without unanticipated toxicities or clinically relevant pharmacokinetic interactions. The recommended dose for chidamide in this combination was established at 20 mg, and a phase II trial is ongoing with this regimen in patients with advanced NSCLC.

Weekly intravenous nanoparticle albumin-bound paclitaxel for elderly patients with stage IV non-small-cell lung cancer:a series of 20 cases

The purpose of this study was to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel as a rescue regimen in the treatment of patients with advanced non-small-cell lung cancer. We retrospectively reviewed the medical records of 20 patients with stage IV non-small-cell lung cancer. The patients had progressive disease after standard antitumor therapy and subsequently received intravenous albumin-bound paclitaxel at the dose of 100 mg/m2 in weekly schedule. Cumulative findings showed that the overall response rate was 30.0%, the disease control rate amounted to 40%, and the 1 year survival rate was 30%. In addition, the median time to progression and the median survival time reached 5 and 10 months, respectively. Meanwhile, no severe hypersensitivity reactions and grade 4 adverse effects were reported. In summary, weekly-administered albumin-bound paclitaxel seems to be an effective and safe regimen for elderly patients with stage IV non-small-cell lung cancer who were refractory to conventional therapy.

Survivin-specific small interfering RNAs enhance sensitivity of glioma U-87MG cells to paclitaxel by promoting apoptosis

A survivin siRNA expression vector was transfected into glioma U-87MG cells and these cells were then treated with paclitaxel. The results showed that survivin-specific siRNA combined with paclitaxel treatment synergistically inhibited glioma U-87MG cell proliferation and promoted apoptosis. This treatment also inhibited the expression of the cell cycle regulatory proteins, survivin cyclinD1, c-Myc and CDK4 and enhanced the sensitivity of U-87MG cells to paclitaxel.

Anti-tumor Activity of Biodegradable Polymer-paclitaxel Conjugated Micelle Against Mice U14 Cervical Cancers

Two kinds of paclitaxel（PTX） conjugate micelles,of which one contained 25%（mass fraction） PTX [M（PTX）] and the other contained 22.5%（mass fraction） of PTX and 1.4%（mass fraction） of folate（FA）[FA-M（PTX）],were prepared for cell apoptosis and anti-tumor activity evaluation on U14 cervical cancer mouse models in comparison with 0.9%（mass fraction） saline（control） and equivalent Taxol.Seven days after tail intravenous injection of the drugs,the mice were sacrificed to measure the tumor masses.The average tumor masses were 4.26,2.89,2.63,and 2.17 g for the control,Taxol,M（PTX） and FA-M（PTX） groups,respectively.The inhibition rates of tumor growth calculated for the three drug groups were 32%,38% and 49%,respectively.Flow cytometry（FC） analysis and terminal deoxynucleotidyl transferase（TdT）-mediated deoxyuridine triphosphate（dUTP） nick end labeling（TUNEL） assay were conducted on the cancer tissues.The cell apoptosis rates based on the FC data and the TUNEL data were 20%,31%,37%,42%,and 10%,22%,26%,34%,respectively,both showing statistically significant differences（P〈0.05） between three drug groups and the control group,and between the FA-M（PTX） group and the other two drug groups.In conclusion,the composite FA-M（PTX） micelles can be used for U14 cervical cancer treatment.

Association between HER2 status and response to neoadjuvant anthracycline followed by paclitaxel plus carboplatin chemotherapy without trastuzumab in breast cancer

Background： We recently showed HER2-positive breast cancers are less likely to respond to neoadjuvant anthracycline chemotherapy. Here, we investigated whether HER2-positive breast cancers responded to sequential neoadjuvant anthracycline followed by paclitaxel plus carboplatin regimen in the absence of trastuzumab. Methods： Women （n=372） with operable primary breast cancer initially received two cycles of neoadjuvant anthracyclines, the clinical tumor response was assessed, then patients were received four cycles of paelitaxel plus carboplatin regimen. All the patients did not received trastuzumab treatment in the neoadjuvant setting. HER2 status was determined by immunohistochemistry and/or by fluorescence in situ hybridization in core- biopsy breast cancer tissue obtained before the neoadjuvant chemotherapy. Results： Eighteen percent （67/372） of patients achieved a pathologic complete response （pCR） in their breast. HER2-positive tumors had a significant higher pCR rate than HER2-negative tumors （33.0% versus 13.5%, P〈0.001） in this cohort of 372 patients, and positive HER2 status remained an independent favorable predictor of pCR in a multivariate analysis [odds ratio （OR）, 2.26; 95% confidence interval （CI）, 1.18 to 4.36, P=0.015]. Furthermore, patients who responded to initial anthracycline regimens were more likely to respond to paclitaxel plus carboplatin than patients who did not （pCR, 27.2% versus 14.6%, P=0.005）. Patients with HER2-positive tumors exhibited a significant higher pCR rate than did patients with HER2- negative tumors in both anthracycline response group （40.5% versus 20.0%, P=0.025） and anthracycline non-response group （28.3% versus 11.3 %, P=0.002）. Conclusions： Under the circumstance of no trastuzumab treatment, women with HER2-positive cancers derive a large benefit from paclitaxel-carboplatin-based neoadjuvant chemotherapy.