Knitted Silk Fibroin‐Reinforced Bead‐on‐String Electrospun Fibers for Sustained Drug Delivery Against Colon Cancer

Bead‐on‐string electrospun fibers containing camptothecin (CPT) are fabricated on the surface of knitted silk fibroin (SF) meshes. Microscopic characterization reveals that the bead‐on‐string structure is prepared successfully and CPT is mainly located within the beaded structure. Interestingly, the CPT‐loaded beaded SF mesh (CPT‐SF mesh) has excellent mechanical properties. More importantly, it is able to perform a sustained CPT release without burst release. In vitro cytotoxicity tests further indicate that the CPT‐SF mesh shows much stronger anticolon cancer activity in comparison with SF meshes and beaded SF meshes. Hence, the CPT‐SF mesh has great potential as a promising local drug delivery system for colon cancer treatment.     

ERCC1对胃癌患者手术及化疗后生存预测的意义

Objective:The aim of this study was to evaluate the effect of the excision repair cross-complementing (ERCC1) expression on survival in advanced gastric cancer patients who underwent surgical resection and treated with oxaliplatin-based adjuvant chemotherapy. Methods: Sixty-three patients who underwent surgical resection for cure and treated with oxaliplatin-based adjuvant chemotherapy were included in this study. The expressions of ERCC1 of gastric cancer were examined by immunohistochemistry and the patients were categorized into ERCC1-(+) and ERCC1-(-) groups. The relation between ERCC1 expression and survival of patients was examined. Results: Of the 63 eligible patients, 36 patients (57.1%) had tumor with a positive expression of ERCC1 and the remaining 27 patients had tumor with a negative ERCC1 expression. Expression differences of ERCC1 didn't correlated with age (P - 0.827), gender (P = 0.12), differentiation (P = 0.113), historical type (P = 0.942), site of tumor (P = 0.221), size of tumor (P = 0.608), stage (P = 0.815) and lymphatic invasion (P = 0.165). Overall survival (OS) was significantly longer in patients without ERCC1 expression, when compared to patients with ERCC1 expression (P = 0.023). Multivariate analysis revealed that ERCC1 expression significantly impacted on OS (MR: 4.049; P = 0.000). Conclusion: We concluded that resected and treated with oxaliplatin-based adjuvant chemotherapy gastric cancer patients without ERCC1 expression have a better survival when compared to patients with ERCC1 expression. ERCC1 expression will hopefully provide a rational basis for improving adjuvant chemotherapeutic strategies for gastric cancer patients. ERCC1, itself, may be a prognostic factor for gastric cancer.     

Co-delivery of paclitaxel and α-tocopherol succinate by novel chitosan-based polymeric micelles for improving micellar stability and efficacious combination therapy

The aim of this study was to develop chitosan derivative polymeric micelles for co-delivery of paclitaxel (PTX) and α-tocopherol succinate (α-TS) to the cancer cells to improve the therapeutic efficiency and reduce side effects of PTX. In this study, amphiphilic tocopheryl succinate-grafted chitosan oligosaccharide was synthesized and physically loaded by PTX and α-TS with entrapment efficiency of 67.9% and 73.2%, respectively. Physical incorporation of α-TS into the micelles increased the hydrophobic interaction between PTX and the micelles core, which improved micelle stability, reduced the micelle size and also sustained the PTX release from the micelles. The mean particle size and zeta potential of αTS/PTX-loaded micelles were about 133?nm and +25.2?mV, respectively, and PTX release was completed during 6–9?d from the micelles. Furthermore, the cytotoxicity of α-TS/PTX-loaded micelles against human ovarian cancer cell line cancer cell in vitro was higher than that of PTX-loaded micelles and the free drug solution. Half maximal inhibitory concentration values of PTX after 48-h exposure of the cells to the PTX-loaded micelles modified and unmodified with α-TS were 110 and 188?ng/ml, respectively.     

Novel Mn3[Co(CN)6]2@SiO2@Ag Core–Shell Nanocube: Enhanced Two‐Photon Fluorescence and Magnetic Resonance Dual‐Modal Imaging‐Guided Photothermal and Chemo‐therapy

The versatile Mn₃[Co(CN)₆]₂@SiO₂@Ag core–shell NCs are prepared by a simple coprecipitation method. Ag nanoparticles with an average diameter of 12 nm deposited on the surface of Mn₃[Co(CN)₆]₂@SiO₂ through S–Ag bonding are fabricated in ethanol solution by reducing silver nitrate (AgNO₃) with NaBH₄. The NCs possess T₁–T₂ dual‐modal magnetic resonance imaging ability. The inner Prussian blue analogs (PBAs) Mn₃[Co(CN)₆]₂ exhibit bright two‐photon fluorescence (TPF) imaging when excited at 730 nm. Moreover, the TPF imaging intensity displays 1.85‐fold enhancement after loading of Ag nanoparticles. Besides, the sample also has multicolor fluorescence imaging ability under 403, 488, and 543 nm single photon excitation. The as‐synthesized Mn₃[Co(CN)₆]₂@SiO₂@Ag NCs show a DOX loading capacity of 600 mg g⁻¹ and exhibit an excellent ability of near‐infrared (NIR)‐responsive drug release and photothermal therapy (PTT) which is induced from the relative high absorbance in NIR region. The combined chemotherapy and PTT against cancer cells in vitro test shows high therapeutic efficiency. The multimodal treatment and imaging could lead to this material a potential multifunctional system for biomedical diagnosis and therapy.     

培美曲塞治疗晚期非小细胞肺癌近期疗效分析

Objective:The aim of our study was to observe the efficacy and toxicity of 50 cases of advanced non-small cell lung cancer (NSCLC) patients treated by pemetrexed.Methods:Fifty patients,including 29 females and 21 males,with a median age 62 years (35–82 years),13 of whom were treated with pemetrexed only and the left 37 cases were treated with pemetrexed combined with platinum in the Department of Oncology,Renmin Hospital of Wuhan University from June 2006 to March 2009.Single agent regimen:patients received pemetrexed 500 mg/m2 on day 1 with every 21 days.Combination regimen:patients received pemetrexed 500 mg/m2 on day 1 and carboplatin 300 mg/m2 on day 1 or cisplatin 35 mg/m2 on day 1 to day 3 or nedaplatin 80 mg/m2 on day 1 by intravenous infusion with 21 days as one cycle.RECIST 1.0 standard was used to evaluate the clinical efficiency,and the WHO toxicity standard was used to evaluate toxic reaction,and the QOL was used to evaluate the quality of life.Results:All patients were given 162 cycles (at least 2 cycles,at most 6 cycles) and the response rate of all the patients were evaluated.There were 2 complete remission (CR),7 partial remission (PR),22 stable disease (SD) and 19 progressive disease (PD) in the group,the overall response rate was (RR) was 18.0% and disease control rate (DCR) 62.0%.The quality of life improvement rate reaches 58.0%.The major toxic reaction included neutropenia,thrombocytopenia,hypemia,nausea,and vomiting.Most of the severity of these effects was grade I–II and well tolerated.Conclusion:Chemotherapy with pemetrexed or pemetrexed combined with platinum in the treatment of advanced non-small cell lung cancer is effective,safe and well-tolerable,which can improve quality of life of the patient.     

紫杉醇联合氟脲嘧啶/亚叶酸钙双周方案二线治疗晚期胃癌的疗效及毒性分析

目的评价紫杉醇联合氟脲嘧啶/亚叶酸钙双周方案二线治疗晚期胃癌的疗效及毒性。方法分析一线化疗失败后采用紫杉醇联合氟脲嘧啶/亚叶酸钙双周方案作为二线化疗方案的48例晚期胃癌患者资料,评价缓解率（RR）、疾病进展时间（TTP）、总生存（OS）及不良反应。治疗方案为：紫杉醇100 mg.m-2,静脉滴注3 h;亚叶酸钙200 mg.m-2,静脉滴注2 h;随后给予氟脲嘧啶400 mg.m-2静脉推注,氟脲嘧啶2.4 g.m-2为微量泵持续泵注46 h。每2周给予1次化疗,每2次为1个疗程。结果 48例患者中,近期缓解率为22.9%,中位TTP及OS分别为3.6月和7.8月,获缓解患者中位OS明显长于未获缓解者（P〈0.05）;患者耐受性良好,主要的不良反应为骨髓抑制、外周神经毒性、脱发、腹泻和肌肉关节疼痛。结论紫杉醇联合氟脲嘧啶/亚叶酸钙双周方案二线治疗PS评分高的晚期胃癌缓解率较高,不良反应可耐受,值得进一步开展前瞻性研究证实。     

Co‐Delivery of Doxorubicin and siRNA with Reduction and pH Dually Sensitive Nanocarrier for Synergistic Cancer Therapy

Drug resistance is the greatest challenge in clinical cancer chemotherapy. Co‐delivery of chemotherapeutic drugs and siRNA to tumor cells is a vital means to silence drug resistant genes during the course of cancer chemotherapy for an improved chemotherapeutic effect. This study aims at effective co‐delivery of siRNA and anticancer drugs to tumor cells. A ternary block copolymer PEG‐PAsp(AED)‐PDPA consisting of pH‐sensitive poly(2‐(diisopropyl amino)ethyl methacrylate) (PDPA), reduction‐sensitive poly(N‐(2,2′‐dithiobis(ethylamine)) aspartamide) PAsp(AED), and poly(ethylene glycol) (PEG) is synthesized and assembled into a core‐shell structural micelle which encapsulated doxorubicin (DOX) in its pH‐sensitive core and the siRNA‐targeting anti‐apoptosis BCL‐2 gene (BCL‐2 siRNA) in a reduction‐sensitive interlayer. At the optimized size and zeta potential, the nanocarriers loaded with DOX and BCL‐2 siRNA may effectively accumulate in the tumor site via blood circulation. Moreover, the dual stimuli‐responsive design of micellar carriers allows microenviroment‐specific rapid release of both DOX and BCL‐2 siRNA inside acidic lysosomes with enriched reducing agent, glutathione (GSH, up to 10 mm ). Consequently, the expression of anti‐apoptotic BCL‐2 protein induced by DOX treatment is significantly down‐regulated, which results in synergistically enhanced apoptosis of human ovarian cancer SKOV‐3 cells and thus dramatically inhibited tumor growth.     

应用脂质体紫杉醇联合顺铂对比白蛋白结合型紫杉醇联合顺铂一线治疗晚期非小细胞肺癌的临床观察

目的：观察脂质体紫杉醇联合顺铂对比白蛋白结合型紫杉醇联合顺铂一线治疗晚期非小细胞肺癌（NSCLC）的临床疗效及预后,同时评价血清乳酸脱氢酶（LDH）在预后的评价的作用。方法62例经病理学证实为晚期的NSCLC患者,按随机数字表法分为白蛋白结合型紫杉醇联合顺铂组（A组,31例）和脂质体紫杉醇联合顺铂组（B组,31例）。分析2组的疗效、不良反应及远期生存。测定血清乳酸脱氢酶（LDH）,并根据化疗后血清LDH变化,分为反应组（下降）和不反应组（升高或持平）。结果A组和B组有效率分别为12．9％和25．8％,疾病控制率分别为90．3％和93．5％,2组比较差异无统计学意义（P＞0．05）。A组中位PFS为17．4个月优于B组9．6个月（95％可信区间,5．2个月to19．7个月,P＝0．264）。亚组分析鳞癌患者应用白蛋白结合型紫杉醇联合顺铂方案化疗优于脂质体紫杉醇联合顺铂。2组主要不良反应为骨髓抑制和消化道反应。Cox多因素分析提示性别、年龄、LDH反应性均是影响预后的独立危险因素;女患者预后较男患者好（HR＝3．231,P＝0．014）,初治时年龄大于60岁的患者预后较好（HR＝0．287,P＝0．005）,LDH反应组比不反应组预后好（HR＝0．379,P＝0．027）。结论脂质体紫杉醇联合顺铂和白蛋白结合型紫杉醇联合顺铂均为较好的治疗方案,LDH反应性可能预测晚期NSCLC患者疗效。     

粗针穿刺活检对乳腺癌患者术后 5 年生存率的影响简

目的：探讨粗针穿刺活检对乳腺癌患者术后5年生存率的影响。方法选取2004-2005年期间行手术切除,且依照个体病情完成了全部治疗方案,随访时间＞5年的乳腺癌患者134例。其中,67例术前进行粗针穿刺活检和新辅助化疗（观察组）,67例同期采用术中快速冰冻病理诊断者为对照组,对2组术后5年生存率进行比较。结果观察组和对照组术后5年生存率分别为78．46％、76．56％,2组比较差异无统计学意义（P＞0．05）。结论粗针穿刺活检和新辅助化疗对乳腺癌术后5年生存率无不良影响。