智能型药物控释可视化系统的构建与表征——高分子实验的新设计与教学实践

介绍一个涵盖高分子化学、物理化学与仪器分析等领域的实验新设计与教学实践。通过水相自由基沉淀聚合法合成一种温敏性微凝胶,并使用紫外-可见分光光度计和动态光散射仪对其温度响应特性进行表征,进而将其用作载体材料以设计构建智能型药物控释系统,利用微凝胶低温溶胀、高温收缩的特性,实现药物的装载、释放。提出结合色彩理论与化学知识来理解药物释放过程,以在可见光区存在明显吸收的药物作为模型药物,将“没有明显实验现象”的药物释放过程“可视化”,以更加直观的方式观测药物释放过程,并在此“可视化”感性认识的基础上,理性分析药物释放过程的分子扩散机理。本实验取材于广受关注且已有较多验证的研究前沿成果,绿色环保,并且可拓展至其他响应性高分子及药物,具有普适性。本实验主要目标是在锻炼学生基本操作能力的同时,培养他们发现问题、解决问题的研究技能,提升学生创新能力。

单药健择治疗老年非小细胞肺癌荟萃分析(英文)

Objective:Gemcitabine,used as single agent for elderly patients with non-small cell lung cancer (NSCLC),was demonstrated effective in this population based on phase II studies.The aim of this study was to summarize all those phase II studies with the hope to get a comprehensive understanding of gemcitabine efficacy.Methods:The PubMed database was used to search all the papers on NSCLC associated with gemcitabine used as single agent in the first line setting till to March 31st,2010.And the medians and their 95% CI of overall response rate (ORR),disease control rate (DCR),progression free survival (PFS),and overall survival (OS) were calculated.Results:1.There were 7 papers including 410 patients with performance status (PS) ≤ 2 and advanced stage collected.2.The dose-intensities of gemcitabine were 843.75 mg/m 2 /week-1125 mg/m 2 /week in the 4-week schedule,and 666.7 mg/m 2 /week in the 3-week schedule.3.The median age was 73.8 (95% CI was 72.44,75.16) years old;36.1% (95% CI:31.4%,40.7%) of patients with stage IIIB and 60.5% (95% CI:55.8%,65.2%) of patients with stage IV;35.9% (95% CI:31.2%,40.5%) patients were adenocarcinomas and 43.7% (95% CI:38.9%,48.5%) patients were squamous cell carcinomas (SCCs).4.The ORR,DCR,PFS/TTP,and OS were 22.3% (95% CI:18.2%,26.5%),58.4% (95% CI:53.5%,63.4%),3.6 (95% CI:2.9,5.15) months and 6.68 (95% CI:5.4,8.11) months,respectively.Conclusion:Gemcitabine as single agent applied in this special population was effective and can be well tolerated under different doses and usage.

贝伐单抗在中国转移性结直肠癌患者中的疗效及不同治疗线数疗效作用分析(英文)

Objective: We aimed to evaluate the effect of bevacizumab in the palliative treatment of Chinese metastatic colorectal cancer(mCRC) and its efficacy in different lines. Methods: Patients of mCRC treated with bevacizumab or not at Sun Yat-sen University Cancer Center from 2005 to 2013 were recruited as the study group and control group. The endpoints were objective response rate(ORR), disease control rate(DCR), overall survival(OS) and progression free survival(PFS). The OS and PFS of first-, second- and third-line treatment groups were compared between study group and control group. Results: The median PFS of the study and the control group were 8.2 months(7.0–9.4 months), 5.7 months(4.7–6.6 months), P = 0.001; OS were 26 months(5.4–130.5 months), 18 months(16.6–19.4 months), P < 0.001, respectively. The ORR and DCR of first-, second- and third-line were 30.3%(20/66), 20%(6/30), 17.6%(3/17) and 97%(64/66), 86.7%(26/30), 100%(17/17). In the first-line chemotherapy group, the OS of the study group and the control group were 22.9(5.4–96.7) months and 18(16.6–19.4) months(P < 0.001); PFS were 9.4(8.4–10.4) months and 5.7(4.7–6.6) months(P < 0.001), respectively. While in the second- and third-line setting, only OS were statistically different, PFS had no significant difference. Conclusion: The combination of bevacizumab and chemotherapy had a promising short-term and long-term efficacy in Chinese mCRC patients than those without bevacizumab regimens, and the effect could be better reflected in the first-line treatment.

肝动脉灌注化疗联合全身化疗作为一线和非一线治疗不可切除肝转移患者的疗效对比(英文)

Objective: The combination of hepatic arterial chemotherapy(HAIC) and systemic chemotherapy(SYC) has potential effect on colorectal cancer(CRC) patients with unresectable hepatic metastasis. The aim of this retrospective study was to investigate the efficacy and safety of this combined therapeutic regimen on Chinese patients based on single institute experiences. Methods: All 54 patients of this retrospective analysis were diagnosed with CRC with unresectable liver metastasis and received combined HAIC and SYC. Among the patients, 23 of them received HAIC plus SYC when they developed liver metastases as first-line treatment(Group 1), and 31 patients received HAIC plus SYC as non-first-line treatment(Group 2). The different efficacy in two groups was analyzed by SPSS 19.0. Results: The overall response rate(ORR) were 52.2% and 25.8% respectively in Groups 1 and 2(P = 0.047), and the disease control rate(DCR) were 65.2% and 35.5% respectively in Groups 1 and 2(P = 0.031). The median progression-free survival(PFS) were 6.8 and 3.3 months(P = 0.002), the median hepatic progression-free survival(H-PFS) were 8.8 and 3.7 months(P = 0.001), and the median overall survival(OS) were 18.8 and 13.7 months(P = 0.121) in Groups 1 and 2, respectively. No fatal reaction was observed and no significant difference of adverse reaction was found in two groups. Grade 3/4 toxic effects included neutropenia(9.7% in Group 2 only), gastrointestinal reaction(8.7% in Group 1 and 6.5% in Group 2), stomatitis(6.5% in Group 2 only) and hyperbilirubinemia(4.3% in Group 1 only). Conclusion: HAIC combined with SYC showed promising efficacy and safe profiles on CRC patients with unresectable liver metastases.

含白蛋白结合型紫杉醇的化疗方案治疗14例晚期胃癌的近期结果分析(英文)

Objective: Albumin-bound paclitaxel (abraxane, ABX) has more favorable efficacy and less toxicity than conventional taxanes. However, the data of ABX in advanced gastric cancer (AGC) treatment is unavailable. The current study was designed to summarize our experience in treating AGC patients with ABX. Methods: The clinical data of patients with AGC who had received at least one cycle of ABX-based chemotherapy in Sun Yat-sen University Cancer Center from January 10th 2010 to May 14th 2012 was retrospectively analyzed. Results: A total of 47 cycles of ABX-containing regimens, with a median of 3 cycles (range:1-8 cycles), were administered to 14 patients. Five(35.7%) partial responses and 6 (42.9%) stable diseases were obtained, with a disease control rate (DCR) of 78.6%. The median progression free survival (PFS) and overall survival (OS) were 3.3 and 10.8 months, respectively. Interestingly,patients in the first-line setting achieved a DCR of 100% (8/8). Neutropenia and thrombocytopenia were the main grade 3/4 adverse events with an incidence of 50% in the whole group. However, only 25% patients (2/8) experienced grade 3 neutropenia when ABX in combination with fluoropyrimidines. Conclusion: The activity of ABX-based regimens as first-line therapy for patients with AGC is remarkable, and the toxicity is mild when ABX combined with fluoropyrimidines. Further prospective clinical trials of ABX-based chemotherapy as first-line treatment for AGC are strongly anticipated.

Bevacizumab在中国癌症患者中使用的安全性和有效性的荟萃分析(英文)

Objective: The aim of this study was to investigate the efficacy and safety profiles of bevacizumab, the commonly used monoclonal antibody and its safety profiles were challenging, based on Chinese cancer patients. Methods: All the papers studied on Chinese cancer patients treated by bevacizumab were found in both databases of Chinese journal database for fulltext and PubMed were collected. The commonly used efficacy index such as disease control rate (CR + PR + SD) and response rate (CR + PR) were analyzed, and the bevacizumab related side effects were analyzed too. Results: (1) There were ten original papers contained total 199 patients who were the candidates to analyze the safety profiles, and 115 patients with colorectal cancer in five papers who were candidates to analyze the efficacy. (2) Nine in ten papers set the dose of bevacizumab in 2.5 mg/kg/week - 5 mg/kg/week, and the biweekly was the standard chemotherapy interval. (3) The disease control rate and response rate in Chinese colorectal cancer patients were 85% (95% CI: 79%-92%) and 61% (95% CI: 52%-70%), respectively. (4) The side effects related to bevacizumab were rare and most of them were grades 1-2, and only one case with grade 4 bleeding was recorded and only two cases with discontinuation of bevacizumab since hemoplysis. Also, the grades 3-4 side effects related cytotoxic agents were not common. Conclusion: This study summarized the data of Chinese cancer patients treated by bevacizumab-contained regimens, and it showed that the monoclonal antibody was effective and safe for Chinese patients as the West patients.

Cetuximab联合化疗二线治疗6例非小细胞肺癌的近期疗效分析(英文)

Objective:Cetuximab combined with chemotherapy has been used to treat non-small cell lung cancer (NSCLC) in recent years, most of them were first line setting.This study was to summarize our experiences in treating NSCLC patients with cetuximab in the non-first line setting.Methods:From October 1st 2006 to December 31st 2009, six NSCLC patients were treated with cetuximab combined standard chemotherapy as non-first line setting in Sun Yat-sen University Cancer Center, China.The short-term efficacies and safeties were analyzed.Results:1.A total of 18 cycles of cetuximab treatment, with a median of two cycles in the whole group.2.There were 6 patients treated as non-first line setting, overall response rate (ORR) was 33.3% (2/6), disease control rate (DCR) was 33.3% (2/6), median time to progression (TTP) was 3.5 (3-4) months, and median OS was 18 (4-28) months.3.There were 50% (3/6) patients occurred acne-like rash within three weeks, their ORR was 66.7% (2/3), and DCR was 66.7% (2/3), however, both of ORR and DCR in patients who didn't occurred acne-like rash were 0% (0/3), the differences of ORR, DCR between two groups were in significant different (P=0.143).4.There was no treatment-associated death and no cetuximab-associated discontinuation.The incidence of acne-like rash was 50% occurred within three weeks, there were two patients suffered side effects associated with chemotherapy.Conclusion:The data of cetuximab application in non-first line setting for patients with NSCLC were rare, and the addition of cetuximab in those population was safe.

含Cetuximab方案治疗非肠癌消化道肿瘤近期疗效——单中心16例经验总结(英文)

Objective: Cetuximab is an effective medicine for colorectal cancer bearing wild type Kras. However, few studies of cetuximab on patients with noncolorectal gastrointestinal cancer were available now. The aim of this study was to summarize the efficacy and safety profiles base-on the experiences of 16 patients with noncolorectal gastrointestinal cancer accepted cetuximab-contained regimens treatment. Methods: The clinical data of all patients with noncolorectal gastrointestinal cancer treated by cetuximab combined with chemotherapy and/or radiotherapy from October 1st 2006 to Jun 30th 2009 in Sun Yat-sen University Cancer Center were collected. Results: (1) A total of 16 patients enrolled, including gastric cancer, esophageal carcinoma, pancreatic cancer and cholangiocarcinoma (8, 6, 1 and 1, respectively). The cetuximab was adminis- tered 92 cycles totally with median cycle of 4. (2) PR, SD and PD obtained in 4, 3 and 2 patients respectively in cetuximab + chemotherapy group. The disease control rate, median TTP and median OS were 77.8% (7/9), 3.5 months and 3.5 months, respectively. (3) Both of patients in cetuximab + radiotherapy group achieved PR with median TTP of 4 months and 7 months, with median OS of 14 and 28 months, respectively. (4) In evaluable patients, 3 PR obtained in first-line setting, 1 PD and 1 SD achieved in second-line setting, 2 SD and 1 PD appeared in third-line and more than third-line setting. (5) The commonly side effect was neutropenia, however, rash and hypomagnesemia were the common side effects related to cetuximab. Conclusion: Cetuximab-contained regimens show a promising disease control rate, especially in first-line setting, in patients with noncolorectal gastrointestinal cancer, and the side effects both related to cytotoxic agents and related to cetuximab itself is tolerable and manageable. Of course, more phase Ⅲ clinical trails are needed urgently.

西妥昔单抗联合化疗一线治疗非小细胞肺癌疗效:基于公开发表文章的总结(英文)

Objective:The combination of cetuximab with standard chemotherapy was not widely studied though it was recommended by NCCN 2009 to apply in non-small cell lung cancer(NSCLC) first-line setting.The aim of this study was to summary the efficacy and safety profiles of all the NSCLC patients available in openly published papers treated with above mentioned regimens.Methods:The PubMed database was used to search all the papers on NSCLC associated with cetuximab treatment, and only the clinical trails applied cetuximab combined with doublets cytotoxic chemotherapy in first-line setting till to 30 November 2009 were collected.And the medians and their 95% CI of objective response rate(ORR), progression free survival(PFS), overall survival(OS), and the common adverse events were calculated.Results:(1) Eight papers including 1032 patients were collected, and all cases were at advanced stage.(2) The ratio of male and female patients was 1.6, 50.1% patients were adenocarcinoma and 28.2% patients were squamous cell carcinoma(SCC), 90.0% patients were PS = 0-1, and 78.2% patients were white ethnic.(3) The disease control rate(DCR), ORR, PFS, and OS were 65.2%(95% CI:60.7%-69.7%), 33.2%(95% CI:30.3%-36.1%), 5.0 months(95% CI:4.7-5.3) and 10.9 months(95% CI:9.6-12.2), respectively.Conclusion:This is the first study to summarize the efficacy and safety profiles of cetuximab combined with chemotherapy in NSCLC first-line setting based on all available patients.The addition of cetuximab caused promising prognosis and acceptable side effects excepting higher incidence of neutropenia, and febrile neutropenia.

Light-mediated CO_(2)-responsiveness of metallopolymer microgels

Here, we report a finding on light-mediated CO_(2)^(-)responsiveness. It is found on the microgels that are made of side-chain type metallopolymers containing metalla-aromatics. Turbidity and laser light scattering studies on dilute aqueous dispersion of these microgels in dark indicate high CO_(2)^(-)responsivity, but poor reversibility upon N2 purge, which can be improved by exposing to light. This light-mediated CO_(2)^(-)responsiveness can be elucidated by the loss of aromaticity from initial photoexcitation and concurrent formation of a less reactive, antiaromatic excited state of relatively low CO_(2) binding affinity, and by subsequent relief of antiaromaticity that can enhance the CO_(2) removal. The finding is also checked by CO_(2) uptake-release experiments on the microgels, which enables both CO_(2) capture of high capacity and CO_(2) removal of good reversibility under a mild condition, allowing effective and reversible response to dilute CO_(2).