Preoperative intra-arterial chemotherapy with docetaxel,cisplatin, and peplomycin combined with intravenous chemotherapy using 5-fluorouracil for oral squamous cell carcinoma

The objectives of this study were to evaluate survival in 141 patients with stage II–IV oral squamous cell carcinoma (OSCC) treated with preoperative intra-arterial chemotherapy with docetaxel, cisplatin, and peplomycin combined with intravenous chemotherapy using 5-fluorouracil (IADCPIVF) via the superficial temporal artery, and to clarify the prognostic factors. The study population included 59 patients with stage II OSCC, 34 with stage III, and 48 with stage IV. After IADCPIVF, 139 patients underwent surgery; minimally invasive surgeries (MIS) including excisional biopsy were performed on 96 patients with a remarkably good response to IADCPIVF. The primary tumour response rate was 99.3% (complete response rate 56.7%, good partial response rate 17.0%, fair partial response rate 25.5%). Additionally, there were no serious adverse events associated with IADCPIVF. The 5-year overall survival rate was 74.6% (stage II 83.6%, stage III 72.7%, stage IV 64.8%). In the multivariate analysis of survival, T classification and clinical tumour response were significant prognostic factors. Eight (8.3%) of the patients who received MIS had primary recurrence and six were salvaged. In conclusion, IADCPIVF is safe and efficacious for treating OSCC, and MIS could reduce the extent of primary tumour resection in the case of a remarkably good response.     

Design and synthesis of novel organometallic complexes using boronated phenylalanine derivatives as potential anticancer agents

Drug design and discovery studies are important because of the prevalence of diseases without available medical cures. New anticancer agents are particularly urgent because of the high mortality rate associated with cancer. A series of mononuclear gold (III) and platinum (II) complexes based on boronated phenylalanine (BPA) were designed and synthesized using 4,4’-dimethyl-2,2’-dipyridyl (L1) or 1,10-phenanthroline-5,6-dion (L2) ligands to obtain promising anticancer drug candidates. Proton nuclear magnetic resonance, infrared, mass spectrometry, and elemental analyses were utilized for chemical characterizations. Cell viability, cancer cell colony formation, endothelial tube formation, and cytoskeleton staining assays were performed using A549 lung adenocarcinoma and human umbilical vein endothelial cells (HUVECs) to investigate preliminary pharmacological activities. L1-based platinum (II) complex (BPA-L1-Pt) was the most promising complex, and has similar activity with the approved chemotherapy drug cis-platinum. Half maximal inhibitory concentration values for BPA-L1-Pt were 9.15 µM on A549s and 16.61 µM on HUVECs; the values for cis-platinum were 5.24 µM on A549s and 23.14 µM on HUVECs. Consequently, further synthesis studies should be performed to boost the cancer cell selectivity feature of BPA by varying metal and ligand types.     

宫颈癌顺铂耐药研究进展

顺铂（DDP）作为第一个被发现的金属抗癌药物，是目前最有潜力和应用最广泛的抗肿瘤药物。顺铂在宫颈癌的治疗中尤为重要，目前已被推荐为同步放化疗的首选药物。但随着广泛的使用，顺铂的耐药性逐渐显露出来，并成为限制临床疗效和部分患者肿瘤治疗进展的主要原因之一。顺铂的耐药机制复杂，发生环节较多，但具体耐药机制尚不明确，目前按照顺铂耐药发生的环节可分为:①顺铂在血液循环过程中产生耐药；②顺铂通过细胞膜的流入或流出产生耐药；③顺铂在胞质中产生耐药；④顺铂与DNA结合后产生耐药。本文综述了宫颈癌顺铂耐药可能发生的四个环节及克服耐药常用的手段，为提高顺铂对宫颈癌的疗效提供依据。     

红参发酵产物联合长春瑞滨及顺铂化疗方案治疗晚期非小细胞肺癌患者的疗效

目的探讨红参发酵产物联合长春瑞滨及顺铂化疗方案治疗晚期非小细胞肺癌患者的疗效。方法将104例晚期非小细胞肺癌患者随机分为治疗组及对照组,每组52例。对照组患者给予单纯长春瑞滨^+顺铂化疗方案,治疗组患者在对照组基础上联合应用红参发酵产物。分别在治疗前后采用疲劳症状量表(FSI)、肺癌治疗功能评价量表(FACT-L)评价两组患者疲劳症状及生活质量,并比较治疗前后两组患者血清肿瘤标志物水平、免疫功能指标水平、药物不良反应及生存情况。结果治疗前,两组患者FSI各维度评分及总分,FACT-L各维度评分及总分,细胞角质蛋白19片段抗原21-1(CYFRA21-1)、神经元特异性烯醇化酶(NSE)、癌胚抗原(CEA)、自然杀伤(NK)细胞、CD3^+、CD4^+、CD8^+、CD4^+/CD8^+水平比较,差异均无统计学意义(P﹥0.05)。治疗后,对照组患者FSI各维度评分及总分均高于治疗前及治疗组;治疗组患者生理状态、情绪状态、对疾病关注度评分及总分均高于治疗前,且生理状态、社会家庭状态、情绪状态、功能状态、对疾病关注度评分及总分均高于对照组;两组患者CEA、CYFRA21-1及NSE水平均较治疗前下降,且治疗组患者均低于对照组患者;治疗组患者NK细胞、CD3^+、CD4^+及CD4^+/CD8^+水平均较治疗前上升,且均高于对照组患者,差异均有统计学意义(P﹤0.05)。治疗组患者血液学不良反应发生例数少于对照组,差异有统计学意义(P﹤0.05)。结论红参发酵产物联合长春瑞滨及顺铂化疗方案能够有效提高晚期非小细胞肺癌患者的免疫功能及生活质量,降低血清肿瘤标志物水平,并减轻血液学不良反应。     

Chemotherapy in the treatment of advanced or recurrent olfactory neuroblastoma

Background: Olfactory neuroblastoma is a rare sino‐nasal tumor arising from the olfactory epithelium and is often characterized by local invasion or metastasis. The role of chemotherapy in the treatment of this tumor is unclear. The purpose of this study was to review our institution’s experience of chemotherapy for advanced or recurrent olfactory neuroblastoma. Methods: Twenty‐one patients with histologically proven olfactory neuroblastoma were treated at our institution between 1992 and 2002. Twelve of these patients received chemotherapy in the setting of unresectable or recurrent disease and were retrospectively reviewed for clinical characteristics, treatment outcome or survival. Results: Eight patients of the 12 patients received cisplatin‐based chemotherapy and the remaining four patients received chemotherapy consisting of docetaxel plus irinotecan (three patients) or cyclophosphamide, doxorubicin, and vincristine (1 patient). A partial response was achieved in five patients, with an overall response rate of 42%, although the chemotherapeutic regimens were heterogeneous. Two partial responses were obtained among the three patients who received docetaxel plus irinotecan. The response rate to chemotherapy was 83% in the younger age group (<40 years), as opposed to 0% in the older age group (≥40 years), and the difference between the two groups was statistically significant (P = 0.02). Conclusion: Our study indicated that olfactory neuroblastoma would be sensitive to chemotherapy, especially with young patients. Docetaxel plus irinotecan has the possibility of showing favorable response, and warrants further investigation.     

亚硒酸钠对顺铂致人体淋巴细胞增殖抑制的拮抗作用

目的 检测亚硒酸钠是否能够削弱或解除顺铂对植物血球凝激素(PHA)刺激的人体外周血淋巴细胞的增殖抑制。方法 用顺铂和亚硒酸钠单独或联合处理PHA刺激的人体外周血淋巴细胞，顺铂(0．05，0．20，0．50mg／L)在细胞培养24h时加入，亚硒酸钠(0．05mg／L)在不同处理中分别在细胞培养开始时加入或与顺铂同时加入；培养72h后检测转化淋巴细胞的有丝分裂指数。结果0．05mg/L亚硒酸钠在培养开始时加入，PHA刺激转化的淋巴细胞有丝分裂指数较对照增长42．8％(P＜0．05)，与顺铂同时加入，有丝分裂指数增长13．7％(P＞0．05)。0．05与0．20mg/L顺铂处理细胞，有丝分裂指数未发生显性改变，当顺铂剂量为0．50mg/L时，细胞有丝分裂指数较对照降低54．5％(P＜0．001)。亚硒酸钠预处理细胞可以解除0．50mg/L顺铂所致的细胞增殖抑制，使有丝分裂指数恢复正常，但亚硒酸钠与顺铂同时加入时，被顺铂抑制的有丝分裂指数只能部分提高。结论0．05mg/L亚硒酸钠单独作用于淋巴细胞可直接促进细胞增殖，与顺铂联合处理细胞时，可降低顺铂毒性，拮抗顺铂的抗增殖作用。亚硒酸钠在细胞培养开始时加入培养体系效果更佳。     

保元排毒丸对顺铂引起的LLC-PK1细胞凋亡干预作用研究

目的：观察保元排毒丸对顺铂（DDP）所致猪肾小管上皮细胞（LLCPK1）凋亡的影响。方法：LLC-PK1细胞分三组培养，空白血清组采用不舍药血清进行培养，模型组分别以10和6μg／mL不同浓度的DDP进行培养，模型＋含药血清组是在不同浓度的DDP基础上予以10％保元排毒丸含药血清进行培养。培养24h后分别以荧光显微镜、电镜、流式细胞仪检测细胞凋亡情况。结果：与空白血清组比较，荧光显微镜下模型组凋亡细胞增多，而模型＋含药血清组凋亡细胞数明显减少；电镜下模型组细胞受损明显，而模型＋含药血清组细胞形态基本正常。流式细胞仪检测细胞凋亡率，空白对照组为2．45％；各DDP组明显增加，10μg／mL组和6／μg／mL组分别为31．80％和30．98％，与空白对照组比较差异有统计学意义，P〈0．001；各含药血清组明显减少，DDP 10μg／mL＋含药血清组和DDP 6μg／mL＋含药血清组分别为15．21％和14．27％，与相应模型组比较差异有统计学意义，P〈0．001。模型组bcl-2基因及突变型p53基因的表达均明显降低，相应含药血清组的表达均有所上调。结论：保元排毒丸能减轻顺铂所致LLC—PK1细胞的凋亡，上调凋亡抑制基因bcl-2和突变型p53，可预防或降低顺铂引起的肾毒性。     

两种化疗方案治疗晚期非小细胞肺癌的对比观察

目的比较化疗方案GP(吉西他滨和顺铂)和IVP(异环磷酰胺、长春地辛和顺铂)治疗晚期非小细胞肺癌(NSCLC)的疗效和毒性.方法将62例晚期NSCLC患者随机分成两组,治疗组30例,采用GP方案:吉西他滨1000 mg/m^2第1、第8 d静脉滴注,顺铂80 mg/m^2第1 d静脉滴注,4周为一周期;对照组32例,采用IVP方案:异环磷酰胺1200 mg/m^2第1～第3 d静脉滴注,长春地辛2.5 mg/m^2第1、第8 d静脉推注,顺铂80 mg/m^2第1 d静脉滴注,4周为一周期.2个周期后评价其疗效及毒性.结果治疗组无一例完全缓解,部分缓解6例,总有效率20.0%;对照组亦无一例完全缓解,部分缓解8例,总有效率25.0%.两组无统计学差异(P＞0.05),但治疗组毒性小于对照组.结论双药化疗方案GP治疗NSCLC的疗效不低于三药方案IVP,且毒副作用轻微,更易为晚期肺癌患者所接受.     

顺铂体外诱导的人肝癌耐药细胞株(QGY/DDP)的建立

目的 建立顺铂(DDP)诱导的人肝癌耐药细胞株(QGY/DDP),研究其生物学特性和耐药机制.方法 采用间歇诱导法,逐步递增DDP浓度,获得耐药细胞株QGY/DDP;MTT法测定药物敏感性;细胞计数法计算倍增时间,流式细胞术检测细胞周期;原子吸收光谱法测定细胞内铂离子蓄积量,流式细胞仪测定P-糖蛋白(P-gp)和谷胱甘肽S-转移酶-π(GST-π)的表达水平.结果 成功建立了顺铂诱导的人肝癌耐药细胞株QGY/DDP,耐药指数为10.81,与5-氟尿嘧啶、长春新碱等抗癌药有明显的交叉耐药;与QGY细胞相比,QGY/DDP细胞增殖减慢、倍增时间延长,G0/G1期细胞增多、S期与G2/M期细胞减少,细胞内Pt含量降低,GST-π的表达升高,而P-gp无明显变化.结论 QGY/DDP细胞具有耐药表型及耐药细胞的生物学特性;其耐药机制与细胞内Pt含量降低和GST-π过表达有关,而与P-gp无关.