TRAIL-DR4启动子区基因多态性与肺癌易感性的相关性研究

[目的]初步探讨TRAIL死亡受体4（DR4）基因多态性与肺癌易感性的关系。[方法]采用PCR-RFLP技术,对92例肺癌患者和92例健康对照者的DR4基因启动子区的-972C/T和-397G/T多态性位点基因型进行检测。以非条件Logistic回归校正混杂因素进行相关性分析。[结果]TRAIL-DR4基因-972C/T位点多态性与肺癌易感性无明显相关性;在吸烟≥20年的人群中含有-397G/T位点T等位基因（GT＋TT）比GG纯合基因型的肺癌发病风险增加（OR=3.462,95%CI：1.222～9.811,P=0.019）。[结论]DR4基因多态性与肺癌的易感性间存在一定的关系。     

非小细胞肺癌患者白细胞介素-6基因多态性研究

目的 探讨中国北方地区人群白细胞介素-6(IL-6)基因启动子单核苷酸多态性(SNP)与非小细胞肺癌(NSCLC)易感性的关联.方法 提取中国北方地区140例NSCLC患者及该地区160例正常对照者外周血基因组DNA,用PCR方法扩增IL-6基因启动子包含-174、-572、-597这3个多态性位点的片段,采用限制性片段长度多态法(RFLP)明确肺癌患者及正常对照者基因型.以非条件Logistic回归校正性别、吸烟、年龄混杂因素,进行多态性与肺癌风险关联性的统计学分析.结果 IL-6基因-174位点均为G/G型,未发现G/C和C/C型;-572位点存在C/C、G/C、G/G 3种基因型;-597位点G/G型占99.3%,仅有2例为G/A型,未发现A/A型.NSCLC组与对照组相比,-572位点基因分布(G/C基因型+G/G基因型与C/C基因型相比)存在显著差异,其基因型频率也明显不同于高加索人群.从不同病理结果来看,风险降低主要发生在肺鳞癌(P=0.004),而与肺腺癌无关(P=0.127).结论 IL-6基因启动子区-572位点多态性与NSCLC易感性显著相关,风险降低主要发生在肺鳞癌,而与肺腺癌无关.     

ERCC1 codon118单核苷酸多态性与非小细胞肺癌铂类化疗的临床预后研究

目的:探讨肿瘤石蜡组织中ERCC1 codon118单核苷酸多态性(single nucleotide polymorphism,SNP)与接受铂类药物化疗非小细胞肺癌(chemotherapy;non-small-cell lung cancer,NSCLC)患者临床预后之间的关系。方法:采用聚合酶链反应-限制性内切酶片段长度多态性(PCR-RFLP)的方法评价47例石蜡包埋NSCLC肿瘤组织中DNA修复基因ERCC1第118位密码子的单核苷酸多态性,并比较不同基因型与NSCLC组织临床病理及铂类化疗预后之间的关系。结果:所有NSCLC患者中位生存时间为16.0月(95%CI,16.4-28.4月),中位无进展生存期为8.0月(95%CI,9.4-16.9月)。ERCC1 codon118与NSCLC临床病理特征均未见相关性。携带ERCC1 C/C基因型的NSCLC患者的中位总生存时间为25.0月,而携带C/T及T/T基因型患者的中位总生存时间仅为10.5月,两者有统计学差异(P=0.012)。携带ERCC1 C/C基因型的NSCLC患者的中位无进展生存期为13.2月,而携带C/T及T/T基因型患者的中位无进展生存期仅为6.0月,两者有统计学差异(P=0.029)。结论:ERCC1 codon118基因单核苷酸多态性与接受铂类药物化疗的NSCLC患者的总生存时间和无进展生存期有关,在一定程度上可以作为判断NSCLC患者铂类药物化疗的预后指标。     

ERCC1 codon118单核苷酸多态性与非小细胞肺癌铂类化疗的临床预后研究

目的：探讨肿瘤石蜡组织中ERCC1 codon118单核苷酸多态性（single nucleotide polymorphism,SNP）与接受铂类药物化疗非小细胞肺癌（chemotherapy;non-small-cell lung cancer,NSCLC）患者临床预后之间的关系。方法：采用聚合酶链反应-限制性内切酶片段长度多态性（PCR-RFLP）的方法评价47例石蜡包埋NSCLC肿瘤组织中DNA修复基因ERCC1第118位密码子的单核苷酸多态性,并比较不同基因型与NSCLC组织临床病理及铂类化疗预后之间的关系。结果：所有NSCLC患者中位生存时间为16.0月（95%CI,16.4-28.4月）,中位无进展生存期为8.0月（95%CI,9.4-16.9月）。ERCC1 codon118与NSCLC临床病理特征均未见相关性。携带ERCC1 C/C基因型的NSCLC患者的中位总生存时间为25.0月,而携带C/T及T/T基因型患者的中位总生存时间仅为10.5月,两者有统计学差异（P=0.012）。携带ERCC1 C/C基因型的NSCLC患者的中位无进展生存期为13.2月,而携带C/T及T/T基因型患者的中位无进展生存期仅为6.0月,两者有统计学差异（P=0.029）。结论：ERCC1 codon118基因单核苷酸多态性与接受铂类药物化疗的NSCLC患者的总生存时间和无进展生存期有关,在一定程度上可以作为判断NSCLC患者铂类药物化疗的预后指标。     

GSTP1基因多态性与非小细胞肺癌遗传易感性和化疗敏感性的相关性研究

目的:探讨Ⅱ相代谢酶谷胱甘肽转硫酶GSTP1基因(105位点)多态性与非小细胞肺癌(non-small celI Iung cancer,NSCLC)遗传易感性以及化疗敏感性关系.方法:采用多聚酶链反应-限制性片段长度多态性(PCR-RFLP)技术,对NSCLC患者和正常人群共204例检测外周血DNAGSTP1 105位点的多态性;102例NSCLC患者选择NP方案化疗,化疗2个周期后评价疗效.结果:以A/A基因型为参照与其他2种G/G和A/G基因型比较,NSCLCGSTP1 105位点分布频率差异无统计学意义,P>0.05.NSCLC患者按照性别、年龄、病理类型及临床分期1:1配比后,以A/A基因型为参照与其他2种基因型比较,敏感组G/G+A/G分布频率(46.43%)高于非敏感组(21.43%),差异有统计学意义(Y2=3.95,P<0.05),携带A/G或G/G等位基因患者较携带A/A基因型者对化疗更为敏感.结论:GSTP1 105位点多态性和NSCLC发病风险无明显关联.携带GSTP1105位点A/G或G/G基因型NSCLC患者,应用NP方案化疗敏感性高于携带A/A基因型患者.     

IL13 Rα2 SNPs在非小细胞肺癌中的表达及其临床意义

目的检测非小细胞肺癌(NSCLC)患者中IL13Rα2 SNPs(rs17095919)的多态性,并探讨其临床意义。方法收集NSCLC患者96例,另选取同期健康体检者40例作为正常对照。SNPs多态性测定应用Real-Time PCR Taqman分析。结果 NSCLC患者C/C、C/T和T/T基因型频率分别为22.9%、51.1%和26.0%,对照组分别为32.5%、30.0%和37.5%,C/C、T/T基因型表达两组间比较无显著性差异(P>0.05),而C/T基因型表达两组间比较具有统计学差异(P<0.05)。C/T基因型表达与NSCLC患者有无吸烟、肿瘤分化程度无显著相关(P>0.05),而与有无淋巴结转移、不同临床病理分期显著相关(P<0.05)。结论 IL13RA2 SNPs(rs17095919)C/T基因型与NSCLC的易感性密切相关,在NSCLC的早期诊断以及预后评估等方面起一定的作用。     

CYP3A5、MDR1和COX-2单核苷酸多态性与晚期非小细胞肺癌化疗疗效关系的探讨

目的 探讨CYP3A5、MDR1和COX-2单核苷酸多态性是否与长春瑞滨、铂类药物对晚期非小细胞肺癌(NSCLC)化疗疗效有关.方法 对69例采用长春瑞滨、铂类方案化疗的晚期NSCLC患者(中国汉族)的CYP3A5(*3)、MDR1 21外显子上的2677 G>T位点、26外显子3435 C>T位点及其单体型和COX-2启动子区的-1195 G>A位点用限制内切酶片段多态性-多聚酶链反应(RFLP-PCR)的方法进行基因分型,结合临床化疗效果进行分析,采用卡方检验分析各位点基因型与化疗疗效之间的关系.结果 MDR1 3435位点野生纯合子(C/C)患者疗效明显高于杂合子(C/T)和突变纯合子(T/T)患者(P=0.033).MDR1 2677位点野生纯合子(G/G)患者疗效明显高于其他基因型患者(P=0.012).MDR1 2677 G-3435 C单体型患者疗效稍高于其他单体型(P=0.063).CYP3A5*3位点基因型与长春瑞滨、铂类方案疗效无关.COX-2-1195 G>A位点野生型(G/G)疗效稍高于其他基因型(P=0.067),但差异无统计学意义.结论 MDR13435 C>T位点基因型和MDR1 2 677 G>A/T位点基因型可以用于预测长春瑞滨、铂类方案对晚期NSCLC患者的疗效.     

非小细胞肺癌RAD51、ERCC2和BAG-1基因多态性的表达

目的:研究DNA修复基因RAD51和着色性干皮病基因(ERCC2/XPD)以及Bcl-2结合抗凋亡基因1(Bcl-2 associated athanogene 1,BAG-1)基因多态性与非小细胞肺癌(non-small cell lung cancer,NSCLC)遗传易感性的关系。方法:采用病例对照研究设计,选取100例非小细胞肺癌病例和80例正常对照。以ERCC2/XPD Lys751Gln和RAD51 codon 135以及BAG-1codon 324基因多态性为研究位点,聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法对多态性进行检测。应用Logistic回归计算OR值及95%CI,比较不同基因型与NSCLC发病风险的关系。结果:ERCC2/XPD 751基因型在病例组的分布频率为C/C型69例(69%)、C/A型26例(30%)和A/A型5例(5%)。与野生基因型C/C型相比,携带ERCC2/XPD C/A基因型和A/A基因型者患NSCLC的危险度比值比(odds ratio,OR)分别是1.53(95%CI:1.15-3.32)和0.58(95%CI:0.15-2.39)。BAG-1 codon 324基因型的分布频率为C/C型81%(81/100)、C/T型19%(19/100)以及T/T型0%(0例)。与野生基因型C/C型相比,携带BAG-1 C/T基因型者患NSCLC的OR是1.28(95%CI:1.08-2.74)。RAD51 codon 135基因型的分布频率为G/G型67%(67/100)、G/C型33%(33/100)、未现C/C型。与野生基因型G/G型相比,RAD51 G/C基因型者患NSCLC的OR是1.03(95%CI:1.06-2.29)。分析结果提示吸烟、环境危险因素与XPD Lys751Gln基因多态存在交互作用,交互效应OR值分别为2.24(95%CI:1.18-2.87)和2.53(95%CI:1.71-3.46),携带XPD Ly s751Gln突变基因者若同时暴露于吸烟、环境危险因素下,则患NSCLC的危险显著增加,相较未暴露于上述因素者,OR值均增大。结论:BAG-1和ERCC2/XPD以及RAD51基因多态性可能与当地居民NSCLC遗传易感性有关,ERCC2/XPD与吸烟、饮酒、环境危险因素存在交互作用。     

GSTP1/RRM1基因多态性与GP方案治疗非小细胞肺癌临床疗效及预后的相关性

目的 探讨谷胱甘肽S转移酶P1(GSTP1)基因A105G和核糖核苷酸还原酶亚单位1(RRM1)基因C37A-T524C多态性与GP化疗方案治疗非小细胞肺癌(NSCLC)临床疗效及预后的相关性.方法 选择84例确诊NSCLC患者为研究对象,采集外周静脉血予以Sanger测序法检测GSTP1 A105G和RRM1 C37A-T524C基因多态性.所有研究对象均接受2个周期GP方案化疗,应用RECIST标准评价患者的临床疗效.统计疾病进展时间(TTP)和总生存时间(OS),分析GSTP1 A105G和RRM1 C37A-T524C多态性与临床疗效及预后的关系.结果 GSTP1 A105G位点3个基因型分布频率分别为:G/G 6.0%、A/G 34.5%和A/A 59.5%,且化疗敏感组患者的105GG基因型分布频率低于化疗非敏感组患者(P<0.01).RRM1 C37A-T524C位点2个基因型分布频率分别为:高有效率38.1%及非高有效率61.9%,且化疗敏感患者的高有效率基因型比例高于化疗非敏感患者(P<0.05).联合多态性分型显示,两组患者105AA/高有效率基因型(A型)、105GG/高有效率基因型(C型)及105GG/非高有效率基因型(F型)比例差异有统计学意义(P<0.05).GSTP1 A105G 3个基因型及RRM1 C37A-T524C 2个基因型中位TTP及中位OS均存在差异(P<0.05).A型患者中位TTP及中位OS最长(P<0.05).结论 同时具有GSTP1 A105A和RRM1 C37A-T524C高有效率基因型的患者行GP化疗方案化疗疗效更好,且预后更佳.     

人肺癌组织MDR1基因多态性与P-gp表达相关性的探讨

目的:探讨人肺癌组织MDR1 C3435T和G2677T/A位点基因多态性与P-gp表达之间是否存在相关性.方法:免疫组化方法分析31例肺癌组织中P-gp的表达量,RFLP-PCR鉴定31例肺癌组织MDR1 C3435T和G2677T/A位点基因型.χ2检验分析基因型与P-gp表达量之间的关系.结果: 两位点基因型分布频率符合Hardy-weinberg平衡.免疫组化结果显示,P-gp表达量有较大差别.经χ2检验,C3435T位点基因型与P-gp表达有关,野生型与突变型和杂合型相比,差异有统计学意义,χ2=7.142,P=0.025.表达量趋势为C/C相似文献   

Compliance with guidelines and correlation with outcome in patients with advanced germ-cell tumours

PurposeTo evaluate prior compliance with guidelines in patients treated with salvage chemotherapy for advanced germ-cell tumours (GCT).Patients and methodsData concerning the initial management of patients requiring salvage chemotherapy for GCT at Institut Gustave Roussy between 2000 and 2010 were obtained and correlated with recommendations for treatment. Criteria of non-compliance were defined based on guidelines. Compliance with guidelines, predictive factors for non-compliance and the impact on outcome were analysed.ResultsAmong 82 patients treated in the salvage setting, guidelines to initial treatment were followed in only 41 cases (50%). The most common non-compliance criteria were non-adherence to the planned dose (16%), an inappropriate interval between first-line chemotherapy cycles (16%), the lack of post-chemotherapy surgery (16%) and a long interval to post-chemotherapy surgery (48%). Compliance with standard care was better in cancer centres than in other hospitals (private or public) (Odd Ratio (OR): 6.9, P = 0.001). A poor-risk status according to the International Germ Cell Cancer Collaborative Group (IGCCCG) was also predictive of compliance in univariate but not in multivariate analysis. No significant difference in outcome after salvage chemotherapy was observed. Patients relapsing after non-compliant first-line therapy tended to be more easily salvaged, which is consistent with the fact that their initial treatment was inadequate. Some of these relapses were therefore probably not due to true biologically refractory disease.ConclusionGuidelines for first-line treatment are adhered to in only half the patients requiring salvage chemotherapy. As the only predictive factor for non-compliance was the treating centre, centralisation of patients with GCT in well-trained hospitals should be recommended.     

Costs associated with complications are lower with capecitabine than with 5‐fluorouracil in patients with colorectal cancer

BACKGROUND:

Capecitabine, an oral alternative to 5‐fluorouracil (5‐FU) in patients with colorectal cancer (CRC), has equal clinical efficacy and a favorable safety profile; however, its use may be limited because of unit cost concerns. In this study, the authors measured the cost of chemotherapy‐related complications during treatment with capecitabine‐ and 5‐FU–based regimens.

METHODS:

Patients with CRC who received at least 1 administration of capecitabine or 5‐FU during 2004 and 2005 were identified from the Thomson MarketScan research databases. Monthly frequency and cost for 23 complications were recorded. Logistic regression was used to predict complication probability. General linear models were used to predict monthly complication cost and total monthly expenditure.

RESULTS:

In total, 4973 patients with CRC met the inclusion criteria for this analysis. Although the most frequently observed complications were the same between capecitabine and 5‐FU (nausea and vomiting, infection, anemia, neutropenia, diarrhea), each was observed with greater frequency in 5‐FU–based regimens. The mean predicted monthly complication cost was significantly higher (by 136%) with 5‐FU monotherapy than with capecitabine monotherapy (difference, $601; 95% confidence interval [95% CI], $469‐$737). In addition, the mean predicted monthly complication cost for 5‐FU+oxaliplatin was higher than the cost with capecitabine plus oxaliplatin (difference, $1165; 95% CI, $892‐$1595). When acquisition, administration, and complication costs were taken into consideration, there were no significant differences in the total cost between capecitabine regimens and 5‐FU regimens.

CONCLUSIONS:

Capecitabine compared well with 5‐FU–based therapy in patients with CRC and was associated with lower complication rates and associated costs. Cancer 2009. © 2009 American Cancer Society.     

Living with secondary breast cancer: coping with an uncertain future with unmet needs

JOHNSTON S.R.D. (2010) European Journal of Cancer Care 19 , 561–563 Living with secondary breast cancer: coping with an uncertain future with unmet needs     

Experience with Impedance Phlebography Compared with Venography

Venography is a particularly reliable method for the diagnosis of deep venous thrombosis but is not suitable as a screening test. Impedance phlebography represents another attempt to discover a simple, non-invasive and reliable method of detecting deep venous thrombosis. It does not, however, meet these criteria.     

再放疗并同步使用Docetaxel在鼻咽癌放疗后复发病人中的应用

目的:不能手术切除的鼻咽癌放疗后再复发的病人,其治疗困难,化疗疗效差,而单独再放疗只能挽救一小部分病人,本文探讨再放疗并同步使用多西紫彬醇(Docetaxel)在鼻咽癌首次放疗后复发病人中可行性及毒副反应,并评价其疗效。方法:对11例鼻咽癌足量放疗后经组织病理学证实复发、而无法行手术及腔内放疗的患者进行了同步放化疗。放疗采用三维适形放疗,外照射鼻咽部,分次量为1.8Gy,总剂量为36Gy-39.6Gy。化疗采用Docetaxel,15mg/m2,每周一次,静脉滴注。结果:10%、33%的患者分别出现Ⅲ度、Ⅳ度皮肤反应,18%、10%的病人分别出现Ⅲ度、Ⅳ度黏膜反应,18%患者出现Ⅲ度恶心呕吐,27%的患者出现Ⅲ度-Ⅳ度白细胞下降,10%患者出现Ⅲ度血小板下降。1例患者因严重的黏膜反应致使治疗延迟2周。治疗结束后,9例(82%)患者达到CR,2例(18%)达到PR,反应率为100%。结论:对于放疗后局部复发的鼻咽癌患者,采用同步放化疗,3D-CRT同时每周使用Docetaxel是可行的,其毒性反应在可以接受的范围内,短期疗效显著。     

Protothecosis successfully treated with amikacin combined with tetracyclines

Summary We report a case of protothecosis in an 18-year-old female student caused by Prototheca zopfii successfully treated with amikacin combined with tetracyclines. Zusammenfassung Es wird über eine Protothecose, verursacht durch Prototheca zopfii, bei einer 18-j?hrigen Studentin berichtet, die erfolgreich mit Amikacin in Kombination mit Tetracyclinen behandelt wurde.