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
Background： The purpose of this study is to evaluate the clinical efficacy and safety of abraxane-based chemotherapy with/without nedaplatin in elderly patients with non-small-cell lung cancer （NSCLC）. Materials an...Background： The purpose of this study is to evaluate the clinical efficacy and safety of abraxane-based chemotherapy with/without nedaplatin in elderly patients with non-small-cell lung cancer （NSCLC）. Materials and methods： From October 2009 to January 2013, 48 elderly patients （≥65 years） with NSCLC were investigated in this clinical trial. The patients were randomized and equally allocated into arms A and AP- （A） abraxane （130 mg/m2, days 1, 8）; （B） abraxane ＋ nedaplatin （20 mg/m2 days 1-3, q3w）. The parameters of objective response rate （ORR）, disease control rate （DCR）, progression-free survival （PFS）, overall survival （OS） and side effects were evaluated between two arms. Results： Over 80% of the patients completed four cycles of chemotherapy. The total ORR was 21.3 %, DCR was 55.3%, PFS 4.5 months and OS 12.6 months. No significant difference was found between arms A and AP in terms of ORR （16.7% vs. 26.1%, P=0.665） or DCR （55.3% vs. 56.5%, P=0.871）. The median PFS in arm A was 3.3 months [25-75% confidence interval （CI）： 3.1-7.2] and 5.5 months （25-75% CI： 3.2-7.0） in arm AP with no statistical significance （P=0.640）. The median OS in arm A was 12.6 months （25-75% CI： 5.7-26.2） and 15.1 months （25-75% CI： 6.4-35.3） in arm AP with no statistical significance （P=0.770）. The side effects were mainly grade 1-2. The incidence of grade 3-4 toxicities was 29.1% in arm A and 62.5% in arm AP with a statistical significance （P=0.020）. Conclusions： Compared with combined therapy, abraxane alone chemotherapy was beneficial for elderly NSCLC patients with better tolerability and less adverse events, whereas did not significantly differ in terms of ORR, DCR, PFS or OS.展开更多
Background: Locally advanced or metastatic pancreatic cancer patients have a poor prognosis with median survival less than 12 months. Nanoparticle albumin bound (nab)-paclitaxel is a novel agent that has demonstrated ...Background: Locally advanced or metastatic pancreatic cancer patients have a poor prognosis with median survival less than 12 months. Nanoparticle albumin bound (nab)-paclitaxel is a novel agent that has demonstrated antitumor effects in cancers that overexpress the albumin binding protein SPARC (secreted protein acidic and rich in cysteine), which includes pancreatic cancer. A recent phase III trial comparing nab-paclitaxel and gemcitabine to gemcitabine alone demonstrated a survival advantage in patients with previously untreated metastatic pancreatic cancer. Here we present our local experience with this drug in patients with gastrointestinal malignancies. Methods: Patients treated with nab-paclitaxel for gastrointestinal malignancies at the Cross Cancer Institute in Edmonton, Alberta, Canada were identified and these patient’s medical records were interrogated for data. Results: Three patients with pancreatic cancer and two with cholangiocarcinoma have been treated with nab-paclitaxel at the Cross Cancer Institute. Three patients achieved stable disease, while one had a partial response, and one had progressive disease after the first assessment. Median time to progression was 3.7 months. Median overall survival (OS) was 32.5 months. Median OS from initiation of nab-paclitaxel was 7.2 months. Patients tolerated treatment with nab-paclitaxel well with only one patient requiring treatment modification due to neutropenia. Conclusion: The experience at this single center supports published evidence that nab-paclitaxel is a safe and effective therapy in pancreatic cancer, but also suggests that it may have activity in cholangiocarcinoma, which to our knowledge is the first published evidence of this in humans.展开更多
Background: Agent targeting HER-2 pathway plus chemotherapy has represented a major progress in the management of patients with breast cancer. However, the role of late-line treatment in heavily pretreated patients is...Background: Agent targeting HER-2 pathway plus chemotherapy has represented a major progress in the management of patients with breast cancer. However, the role of late-line treatment in heavily pretreated patients is still largely unclear. In the last decade, nab-paclitaxel has shown significant activity and good toxicity profile in metastatic breast cancer. Case Presentation: We report the case of a 76-year-old Caucasian woman with metastatic HER-2 positive ductal infiltrating breast carcinoma treated with a combination of weekly nab-paclitaxel and trastuzumab as fifth-line therapy. She had previously received first-line paclitaxel and trastuzumab, second-line vinorelbine and trastuzumab, third-line TDM1 and fourth-line oral capecitabine and lapatinib. Clinical and radiological staging showed progression at bone, skin and soft-tissue. The patient received weekly nab-paclitaxel plus trastuzumab. Massive objective response was clinically and PET documented which lasted 8 months. Tolerance to treatment was fairly good as well as cardiac safety. Conclusion: To the best of our knowledge, this is the first reported case of efficacy of nab-paclitaxel in combination with trastuzumab as fifth-line of treatment in a patient with metastatic HER-2 positive breast cancer.展开更多
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）]...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.展开更多
Anti-HER2 monoclonal antibody （Sc7301）-paclitaxel （TAX） immunoconjugate was pre- pared and its specific binding to tumor cells was investigated in this study. Sc7301 was conjugated to TAX by the active ester metho...Anti-HER2 monoclonal antibody （Sc7301）-paclitaxel （TAX） immunoconjugate was pre- pared and its specific binding to tumor cells was investigated in this study. Sc7301 was conjugated to TAX by the active ester method and then the TAX-Sc7301 immunoconjugate was obtained. After purification and labeling by Cyano-fluorescein isothiocyanate （FITC）, the specific binding of TAX-Sc7301 to HER2-positive tumor cells （SKOV3） and HER2-negative tumor cells （HepG2） was evaluated respectively. TAX-Sc7301 （20 nmol/L） showed distinct specific binding to SKOV3 cells rather than HepG2 cells. And the uptake of the immunoconjugate by SKOV3 cells was increased with the TAX-So7301 concentration （3-48 nmol/L） and the incubation time （P〈0.05）. It was concluded that the TAX-Sc7301 immunoconjugate is ootentially applicable as a targeted agent against HER2-10ositive tumor cells.展开更多
目的探索敲低CXCL8对宫颈鳞状细胞癌紫杉醇化疗疗效的影响,并深入探究其潜在的作用机制。方法采用宫颈癌Hela细胞系,通过慢病毒介导的RNA干扰(RNAi)技术特异性地抑制CXCL8基因的表达。以HitransG P、复感染指数(multiplicity of infecti...目的探索敲低CXCL8对宫颈鳞状细胞癌紫杉醇化疗疗效的影响,并深入探究其潜在的作用机制。方法采用宫颈癌Hela细胞系,通过慢病毒介导的RNA干扰(RNAi)技术特异性地抑制CXCL8基因的表达。以HitransG P、复感染指数(multiplicity of infection,MOI)=100为最佳转染条件,CCK-8实验筛选嘌呤霉素最佳干预浓度为1.5μg/mL;按最佳转染条件将LV-CXCL8-RNAi(3靶点)和阴性对照慢病毒转染至Hela细胞中,并设置空白对照组,qRT-PCR实验选定sh-CXCL8-13组慢病毒为后续实验的干预序列及病毒。实验分为空白对照组、阴性对照组、sh-CXCL8组、紫杉醇组以及sh-CXCL8+紫杉醇组。通过CCK-8实验和细胞侵袭实验评估Hela细胞的增殖活性及侵袭能力,利用qRT-PCR和Western blot实验检测CXCL8、Bcl2、Bax及β-actin的表达水平。结果与其余四组相比,sh-CXCL8+紫杉醇组Hela细胞活性及侵袭性显著降低,差异有统计学意义(P<0.05)。qRT-PCR结果显示,sh-CXCL8+紫杉醇组中CXCL8、Bcl2、PIK3CB以及Akt1基因的表达量显著降低,Bax基因表达量明显上升,组间差异有统计学意义(P<0.05)。Western blot实验结果显示,sh-CXCL8+紫杉醇组中CXCL8、PIK3CB和p-Akt1蛋白的表达量降低(P<0.05)。结论敲低CXCL8可以降低Hela细胞增殖与侵袭能力,可能是通过影响PI3K/Akt通路来影响Hela细胞对紫杉醇的药物敏感性。展开更多
基金National Key Technologies R&D Program for New Drugs(Grant No.2009ZX09301-002,2009ZX09304-004).
文摘The preparation of polymer-anticancer drug conjugates is an effective way to improve the efficacy and decrease the toxicity of anticancer drugs. Polymer-drug conjugates, which were made by combining a suitable polymeric carrier, a biodegradable linker and a bioactive anticancer agent, could form the basis of a new generation of anticancer agents. Poly （L-glutamic acid）- paclitaxel conjugate is a polymer-drug conjugate that links anticancer agent paclitaxel （PTX） to poly （L-glutamic acid） （PG）. PG-PTX conjugate can improve the anticancer activity, enhance the safety and efficacy, and improve the pharmacokinetic properties of PTX. Therefore, the application of PG-PTX facilitates the clinical therapy of a variety of human cancers.
文摘Background： The purpose of this study is to evaluate the clinical efficacy and safety of abraxane-based chemotherapy with/without nedaplatin in elderly patients with non-small-cell lung cancer （NSCLC）. Materials and methods： From October 2009 to January 2013, 48 elderly patients （≥65 years） with NSCLC were investigated in this clinical trial. The patients were randomized and equally allocated into arms A and AP- （A） abraxane （130 mg/m2, days 1, 8）; （B） abraxane ＋ nedaplatin （20 mg/m2 days 1-3, q3w）. The parameters of objective response rate （ORR）, disease control rate （DCR）, progression-free survival （PFS）, overall survival （OS） and side effects were evaluated between two arms. Results： Over 80% of the patients completed four cycles of chemotherapy. The total ORR was 21.3 %, DCR was 55.3%, PFS 4.5 months and OS 12.6 months. No significant difference was found between arms A and AP in terms of ORR （16.7% vs. 26.1%, P=0.665） or DCR （55.3% vs. 56.5%, P=0.871）. The median PFS in arm A was 3.3 months [25-75% confidence interval （CI）： 3.1-7.2] and 5.5 months （25-75% CI： 3.2-7.0） in arm AP with no statistical significance （P=0.640）. The median OS in arm A was 12.6 months （25-75% CI： 5.7-26.2） and 15.1 months （25-75% CI： 6.4-35.3） in arm AP with no statistical significance （P=0.770）. The side effects were mainly grade 1-2. The incidence of grade 3-4 toxicities was 29.1% in arm A and 62.5% in arm AP with a statistical significance （P=0.020）. Conclusions： Compared with combined therapy, abraxane alone chemotherapy was beneficial for elderly NSCLC patients with better tolerability and less adverse events, whereas did not significantly differ in terms of ORR, DCR, PFS or OS.
文摘Background: Locally advanced or metastatic pancreatic cancer patients have a poor prognosis with median survival less than 12 months. Nanoparticle albumin bound (nab)-paclitaxel is a novel agent that has demonstrated antitumor effects in cancers that overexpress the albumin binding protein SPARC (secreted protein acidic and rich in cysteine), which includes pancreatic cancer. A recent phase III trial comparing nab-paclitaxel and gemcitabine to gemcitabine alone demonstrated a survival advantage in patients with previously untreated metastatic pancreatic cancer. Here we present our local experience with this drug in patients with gastrointestinal malignancies. Methods: Patients treated with nab-paclitaxel for gastrointestinal malignancies at the Cross Cancer Institute in Edmonton, Alberta, Canada were identified and these patient’s medical records were interrogated for data. Results: Three patients with pancreatic cancer and two with cholangiocarcinoma have been treated with nab-paclitaxel at the Cross Cancer Institute. Three patients achieved stable disease, while one had a partial response, and one had progressive disease after the first assessment. Median time to progression was 3.7 months. Median overall survival (OS) was 32.5 months. Median OS from initiation of nab-paclitaxel was 7.2 months. Patients tolerated treatment with nab-paclitaxel well with only one patient requiring treatment modification due to neutropenia. Conclusion: The experience at this single center supports published evidence that nab-paclitaxel is a safe and effective therapy in pancreatic cancer, but also suggests that it may have activity in cholangiocarcinoma, which to our knowledge is the first published evidence of this in humans.
文摘Background: Agent targeting HER-2 pathway plus chemotherapy has represented a major progress in the management of patients with breast cancer. However, the role of late-line treatment in heavily pretreated patients is still largely unclear. In the last decade, nab-paclitaxel has shown significant activity and good toxicity profile in metastatic breast cancer. Case Presentation: We report the case of a 76-year-old Caucasian woman with metastatic HER-2 positive ductal infiltrating breast carcinoma treated with a combination of weekly nab-paclitaxel and trastuzumab as fifth-line therapy. She had previously received first-line paclitaxel and trastuzumab, second-line vinorelbine and trastuzumab, third-line TDM1 and fourth-line oral capecitabine and lapatinib. Clinical and radiological staging showed progression at bone, skin and soft-tissue. The patient received weekly nab-paclitaxel plus trastuzumab. Massive objective response was clinically and PET documented which lasted 8 months. Tolerance to treatment was fairly good as well as cardiac safety. Conclusion: To the best of our knowledge, this is the first reported case of efficacy of nab-paclitaxel in combination with trastuzumab as fifth-line of treatment in a patient with metastatic HER-2 positive breast cancer.
基金Supported by the National Natural Science Foundation of China(Nos.20674084,21004062,51103148)the National Basic Research Program of China(No.2009CB930102)the National High-Tech Research and Development Program of China(No.2007AA03Z535)
文摘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.
基金supported by a grant from the National Natural Science Foundation of China(No.30300429)
文摘Anti-HER2 monoclonal antibody （Sc7301）-paclitaxel （TAX） immunoconjugate was pre- pared and its specific binding to tumor cells was investigated in this study. Sc7301 was conjugated to TAX by the active ester method and then the TAX-Sc7301 immunoconjugate was obtained. After purification and labeling by Cyano-fluorescein isothiocyanate （FITC）, the specific binding of TAX-Sc7301 to HER2-positive tumor cells （SKOV3） and HER2-negative tumor cells （HepG2） was evaluated respectively. TAX-Sc7301 （20 nmol/L） showed distinct specific binding to SKOV3 cells rather than HepG2 cells. And the uptake of the immunoconjugate by SKOV3 cells was increased with the TAX-So7301 concentration （3-48 nmol/L） and the incubation time （P〈0.05）. It was concluded that the TAX-Sc7301 immunoconjugate is ootentially applicable as a targeted agent against HER2-10ositive tumor cells.
