乳腺癌患者外周血循环肿瘤细胞与临床特征的关系

目的:探讨乳腺癌患者循环肿瘤细胞(CTCs)检测与临床特征之间的关系及其应用价值.方法:运用叶酸受体细胞检测试剂盒对乳腺癌和正常乳腺疾病患者各132例进行CTCs检测,分析CTC与患者临床特征的关系.结果:132例乳腺癌患者循环肿瘤细胞的阳性率为40.85％,而在乳腺良性疾病组中没有检出CTCs,两组间阳性率差异具有显...     

Matrilin-1基因多态性与青少年特发性脊柱侧凸易感性的关系

疾病严重程度有关.     

大肠癌患者外周血循环肿瘤细胞的检测及临床意义

大肠癌是最常见的癌症之一,尽管转移患者采取化疗和手术联合治疗后生存率已经有所提高,但是长期存活的患者仍然少之又少.循环肿瘤细胞(CTC)检测是最近兴起的技术,其临床意义已被讨论了将近一个多世纪.科技的日新月异使CTC的检测变得更加可行,最近的研究都相似地揭示CTC可以预测结直肠癌转移患者的临床结局.此篇综述将讨论CTC...     

CHRNA1基因多态性对罗库溴铵肌松效应的影响

目的 探讨CHRNA1基因多态性对罗库溴铵肌松效应的影响.方法 择期全麻下行腹部手术患者95例,ASA分级Ⅰ或Ⅱ级,性别不限,年龄18～64岁,体重指数18～25 kg/m2,腋温36～37℃.患者来自河北省或周边地区,且均为汉族,彼此无血缘关系.术前采集外周静脉血样5 ml,EDTA抗凝,蛋白酶K消化,饱和氯化钠盐析法提取DNA.采用聚合酶链反应-限制性片段长度多态性技术和序列分析法对CHRNA1上游478 bp处AG多态性位点rs16862847进行检测,根据基因型将患者分为野生型纯合子组(AA组,n=71)、突变型杂合子组(AG组,n=19)和突变型纯合子组(GG组,n=5).人室后静脉注射芬太尼4μg/kg和异丙酚2 mg/kg,意识消失后启动TOF-Watch SX型加速度肌松监测仪单刺激模式监测拇内收肌颤搐程度,随后静脉注射罗库溴铵0.2 mg/kg,观察肌松效应.结果 与AA组相比,AG组和GG组肌松起效时肌颤搐程度降低(P＜0.05).AG组和GG组肌松起效时肌颤搐程度比较差异无统计学意义(P＞0.05).结论 CHRNA1基因多态性可影响患者罗库溴铵的肌松效应,提示遗传因素是导致肌松药药效个体差异的原因之一.     

乳腺癌转移抑制基因1抑制乳腺癌转移的作用机理研究进展

目的综述乳腺癌转移抑制基因1（BRMS1）在抑制乳腺癌转移中的作用机理研究进展。方法采用文献回顾的方法，对目前国内、外有关BRMS1在乳腺癌中的研究状况加以分析与综述。结果BRMS1与其他肿瘤转移抑制基因一样，主要抑制肿瘤的转移，并不影响肿瘤的生长，在乳腺癌中主要通过调节细胞间的信号转导及其他转移抑制基因的表达而抑制乳腺癌的转移。结论对BRMS1基因的深入研究有助于进一步深化对乳腺癌转移的认识，为肿瘤转移的分子诊断和基因治疗提供新的思路。     

可手术乳腺癌患者外周血循环肿瘤细胞阳性对围手术期凝血功能的影响

目的 分析可手术乳腺癌患者外周血循环肿瘤细胞（circulating tumor cell,CTC）阳性对围手术期凝血功能的影响。方法 选择2019年7月至2020年3月湛江中心人民医院行手术治疗的80例乳腺癌患者,根据其外周血循环肿瘤细胞水平分为阳性组（术前CTC阳性）和阴性组（术前CTC阴性）,分别在术前、术后第1天、术后第3天、术后第7天、术后第14天进行常规凝血功能指标和血栓弹力图检测,比较两组凝血功能、血栓弹力图检测结果。结果 80例患者中CTC阳性12例,阳性检出率15.00%。阳性组与阴性组术前、术后不同时间纤维蛋白原、D-二聚体水平无显著差异（P> 0.05）。阳性组患者凝血酶原时间、活化部分凝血酶时间、血栓弹力图反应时间及凝血时间显著短于阴性组,且血小板计数、血栓弹力图最大振幅、Angle角明显高于阴性组,差异均有显著性（P <0.05）。结论 术前CTC阳性可手术乳腺癌患者围手术期存有凝血功能异常,有潜在深静脉血栓栓塞症发生风险。     

乳腺癌易感性与CYP19基因rs4646、rs1008805多态性的相关性

目的 探讨乳腺癌易感性与CYP19基因rs4646(C/A)、rs1008805(A/G)多态性的相关性.方法 采用病例对照研究,应用TaqMan法检测233例浙江地区乳腺癌患者及180例正常人CYP19基因rs4646、rs1008805多态性,基因型分布和乳腺癌发病风险、患者年龄、月经状态及肿瘤临床病理特征的关系采用行x列表X2检验;危险度比值比(OR)及95%可信区间(CI)运用非条件Logistic回归分析计算.结果 (1)病例组中,CYP19基因rs4646(C/A)位点CC、AC、AA基因型的频率分别为47.6%、41.6%、10.7%,而对照组中则分别为52.8%、38.3%、8.9%;病例组中,C、A等位基因的频率分别为68.5%、31.5%,而对照组中则分别为71.9%、28.1%.以CC型为对照,AC、AA型没有增加乳腺癌的发生风险(P>0.05),经年龄分层,亦未发现其与乳腺癌易感性相关.(2)病例组中,CYP19基因rs1008805(A/G)位点从、AG、GG基因型的频率分别为44.6%、43.3%、12.0%,而对照组中则分别为51.4%、40.2%、8.4%;病例组中,A、G等位基因的频率分别为66.3%、33.7%.而对照组中则分别为71.5%、28.5%.以AA型为对照,AG、GG型没有增加乳腺癌的发生风险(P>0.05),经年龄分层,亦未发现其与乳腺癌易感性相关.(3)CYP19基因rs4646(CA/A)和rs1008805(X/G)多态性与乳腺癌患者年龄、月经状况及病理特征均无明显相关.结论 CYP19基因m4646、rs1008805多态性与乳腺癌易感性无明显相关,尚不推荐单独作为未来乳腺癌基因筛查的候选指标.     

人端粒保护蛋白1基因单核苷酸多态性与胃癌的关系

目的 探讨人端粒保护蛋白1基因(hPOT1)IVS13-98G/T位点单核苷酸多态性与胃癌的关系.方法 收集2005年12月至2006年7月甘肃省武威肿瘤医院、武威市人民医院、武威市凉州区医院168例胃癌患者(胃癌组)和156例健康受试者(对照组)的血液标本,采用聚合酶链反应和限制性片段长度多态性技术行基因型分析,比较各基因型分布频率与胃癌发病风险的关系.采用X~2检验比较胃癌组和对照组hPOT1IVS13-98G/T位点的基因型分布和等位基因频率,用Hardy-weinberg平衡检验基因型和等位基因频率分布是否具有群体代表性.相对危险度和95%CI以非条件Logistic回归模型计算.结果 胃癌组hPOT1IVS13-98G/T位点GG、GT、TT型的频率分别为21.4%、41.7%、36.9%,G、T等位基因的频率分别为42.3%、57.7%;对照组GG、GT、TT型的频率分别为24.4%、51.9%、23.7%,G、T等位基因频率分别为49.7%和50.3%.两组G、T等位基因型频率比较差异无统计学意义(X~2=3.58,P>0.05).以TT型作为参照基因型,GT和GG两种基因型相对危险度分别为0.439(95%CI:0.251～0.767,P<0.05)、0.514(95%CI:0.264～0.999,P=0.05).hPOT1IVS13-98G/T位点各基因型与性别、吸烟及肿瘤家族史对胃癌发病没有影响.结论 hPOT1IVS13-98G/T位点的CT和GG型可能与胃癌的易感性降低有关,hPOT1IVS13-98G/T位点单核苷酸多态性可能为胃癌的保护因素.     

单核苷酸多态性与乳腺癌化疗应答

目的探讨单核苷酸多态性（SNP）与乳腺癌常规化疗药物治疗应答间的相关性及其在指导个体化治疗中的价值。方法检索Pub-Medline和中国CHKD期刊数据库，对近年来此领域有代表性的文献进行整理、归纳。结果多种药物代谢相关基因存在SNP现象，且与药物效应个体多样性有着密切联系。人种、地域、环境、基因间或药物间相互作用可能会对这种关系产生影响。结论SNP研究对于优化个体用药具有重要的应用前景，但多基因多SNP组合分析以及大样本、前瞻性随机对照研究还非常必要。     

乳腺癌骨髓播散肿瘤细胞和免疫微环境的检测

目的 对可手术的乳腺癌患者进行骨髓播散肿瘤细胞的检测，并对骨髓免疫微环境进行研究。方法 联合应用上皮膜抗原（EMA）和细胞角蛋白19（CK19），采用免疫组织化学的方法检测骨髓中的微小转移灶，用流式细胞仪的方法比较不同组间免疫指标的差异。结果 72例乳腺癌患者中，30例（41．7％）骨髓中存在微小转移灶。原发灶肿块大于5cm，p53蛋白表达阴性的患者易发生骨髓微小转移。在乳腺癌患者中，骨髓播散肿瘤细胞阳性的患者比阴性的患者具有较高的记忆CD4^＋T细胞比例，记忆CD4^＋T细胞／记忆CD8^＋T细胞比值。结论 联合应用EMA和CK19进行骨髓播散肿瘤细胞检测的方法是可行的。骨髓播散肿瘤细胞转变成为大体转移的患者，是否与其记忆T细胞水平低下相关需作进一步研究。     

乳腺癌发病风险及侵袭特性与白细胞介素-8和CXCR2基因多态性的关系

目的 探讨细胞因子白细胞介素( 1L)-8(- 251)位点及其受体CXCR2(±1208)位点多态性与乳腺癌发病风险及侵袭特性的关系.方法 采用等位基因特异-聚合酶链反应(AS-PCR)分析方法检测228名乳腺癌患者和100例健康对照者的IL-8(- 251)位点及其受体CXCR2(±1208)位点多态性分布,并进行统计学分析.结果 IL-8(- 251)位点TA型和AA型以及CXCR2(± 1208) TT型是乳腺癌的高危基因型[比值比(OR)=1.57,95％可信区间(CI)=1.08～2.32;OR =2.68,95％ CI=1.26 ～2.99;0R=2.02,95％CI=1.08～3.62],在两组间表达频率的差异有统计学意义(P＜0.05).携带1个及以上高危基因型增加患乳腺癌的风险.分层分析表明携带IL-8(-251)等位基因A和CXCR2(± 1208)等位基因T增加乳腺癌的侵袭特性,其分布频率在肿瘤的高组织学分级(OR=1.95,P＜0.01;OR=1.52,P＜0.05)和淋巴结转移阳性(OR=1.65,P＜0.05;0R=1.66,P＜0.01)中差异有统计学意义.另外,IL-8(-251)A等位基因与ER( -)乳腺癌显著相关( OR=1.65,P＜0.05).结论 IL-8和CXCR2的基因多态性可能与女性乳腺癌的发生发展关系密切,可作为乳腺癌早期基因诊断的指标.     

The significance of circulating tumour cells in breast cancer: A review

Haematogenous spread of circulating tumour cells (CTCs) is the principle mechanism for development of metastases. Research into the enumeration and characterisation of CTCs, particularly in the last decade, has allowed the introduction of semi-automated CTC assessment in the clinical setting. In breast cancer, CTC enumeration is being used as a prognostic biomarker, a predictive biomarker of treatment response and is being assessed to guide treatment in both the early and metastatic setting. CTC characterisation has the potential to direct targeted therapies, such as HER2 therapies in HER2 negative primary breast tumour patients. However, CTC assessment has considerable challenges. Capture and identification of these very rare cells is currently largely dependent on a presumed homogeneity of phenotype. In addition, high throughput assays are lacking. The clinical significance of CTCs is incompletely understood. A large proportion of CTC positive patients have no evidence of metastases, raising the issue of either inconsequential tumour dormancy or non-viable CTCs. CTCs may have additional clinical sequelae such as promoting venous thrombosis. However CTCs provide a real-time liquid biopsy of the tumour and represent an exciting, minimally invasive method of assessing disease status and also a novel therapeutic target for malignancy.     

循环肿瘤细胞在乳腺癌中的研究进展

乳腺癌是女性最常见的恶性肿瘤,复发和转移是导致其死亡的主要原因.研究显示,早期存在于外周血中的循环肿瘤细胞是乳腺癌复发和转移的根源.常规影像学检查多不能在早期发现微小转移病灶,而循环肿瘤细胞取材方便且可重复取材,可为实时监测乳腺癌的进展提供及时有效的信息.目前研究表明,循环肿瘤细胞在乳腺癌的实际临床应用中,可应用于3个方面:(1)实时监测乳腺癌的治疗效果;(2)检测循环肿瘤细胞的分子分型,寻找新的治疗靶点,实现乳腺癌的个体化治疗;(3)提取并培养肿瘤细胞,进行临床药敏试验.虽然循环肿瘤细胞在乳腺癌中的价值已经得到了普遍认可,但其在临床应用中,仍受多种因素的制约.本文就目前循环肿瘤细胞在乳腺癌应用中的进展进行综述.     

结直肠癌中MDR1和ABCG2基因多态性与伊立替康疗效及不良反应的关系

目的研究MDRl和ABCG2基因单核苷酸多态性（SNP）与结直肠癌患者伊立替康（CPT-11）化疗疗效及不良反应的关系。方法回顾性收集北京大学肿瘤医院消化肿瘤内科1996年1月至2011年12月行以CPT．11为基础化疗药物的晚期结直肠癌患者的完整临床资料及血液样本,提取血液DNA,用直接测序法检测MDRl和ABCG2基因SNP．分析基因多态性与CPT-11疗效和不良反应的相关性。结果MDR12677G〉T／A及ABCG2421C〉A、34G〉A和376C〉T的血标本及肿瘤组织检测SNP结果一致率高,分别为94．4％（34／36）、94．6％（35／37）、95．0％（38／40）和97．2％（35／36）。MDR12677G〉T／A中,野生型（G／G）患者较突变型患者临床获益率高．但差异无统计学意义（P〉0．05）;且在二线化疗的患者中,野生型患者无进展生存期（PFS）明显优于突变型患者（P=0．012）。未观察到ABCG2421C〉A、34G〉A和376C〉T多态性与化疗疗效有相关性（均P〉0．05）。同时,未观察到MDR12677G〉T／A、ABCG2421C〉A、ABCG234G〉A和ABCG2376C〉T多态性与患者3度以上粒细胞减少及腹泻相关。结论在晚期结直肠癌患者中,MDR12677G〉T／A可能作为分子标记物来预测伊寺替康方案化疗疗效。     

乳腺癌循环肿瘤细胞临床应用的相关研究

乳腺恶性肿瘤的复发和转移,是乳腺癌患者的主要致死原因。如何早期发现乳腺恶性肿瘤细胞的转移并及时予以治疗,是目前研究的热点。循环肿瘤细胞(circulating tumor cell,CTC)的发现有望为乳腺癌的诊断和治疗提供新的思路。检测CTC有助于早期发现肿瘤的微转移,指导个体化治疗,评价治疗效果及预后。我们对CTC的研究进展进行综述。     

CALM2基因多态性与青少年特发性脊柱侧凸遗传易感性的关联性研究

目的探讨钙调蛋白2基因（CALM2基因）与青少年特发性脊柱侧凸遗传易感性的相关性。方法采集北京协和医院骨科确诊的汉族青少年特发性脊柱侧凸患者107例,对照组107例,病例组按照PUMC分型进行分组。采外周血试剂盒提取DNA。根据国际人类基因组单倍体型图计划提供的基因型数据,选取CALM2基因的SNPs位点,应用VeraCode GoldenGate Genotyping Assay基因芯片进行SNPs基因型鉴定。用关联分析法探索CALM2基因与患者发病及临床表型之间的关系。结果 CALM2的rs10153674等位基因在病例组和对照组中的分布频率统计学上存在显著差异（P=0.003）,rs10153674位点等位基因G与AIS的易感性升高有关。结合PUMC分型,rs10153674和rs1027478基因型在PUMCI型和对照组中的分布频率统计学上存在显著差异（P值分别为0.038,0.006）,rs10153674基因型G/G、rs1027478基因型A/G与PUMCI型的发生有关。结论 CALM2基因遗传变异可能与青少年特发性脊柱侧凸发生相关,有可能是影响AIS易感性的重要因素。PUMCI型AIS的发生可能与rs10153674和rs1027478基因型多态性有关。     

单核苷酸多态性与前列腺癌的研究进展

前列腺癌是影响西方国家男性健康的常见恶性肿瘤,而单核苷酸多态性(SNPs)作为第3代遗传标记可以影响到前列腺癌的发生、发展及预后。相同SNPs在不同种族间和前列腺癌的关系可能存在差异;本文就与前列腺癌相关的基因进行分类,描述不同SNPs与前列腺癌的关系。SNPs可以预测前列腺癌治疗过程中可能的不良反应,同时也可预测前列腺癌的患病风险,但目前仍存在一定的局限。     

Patterns of metastatic spread in early breast cancer

AimsThe aim of this study was to prospectively investigate metastatic pathways of spread to lymph node versus bone marrow and identify biological characteristics that determine these patterns in early invasive breast cancer.Patients and methodsIn all, 177 patients with early invasive breast cancer underwent surgical extirpation of the primary tumour with sentinel lymph node biopsy (SLNB). Bone marrow (BM) aspiration was performed to screen for cytokeratin-positive cells by immunocytochemistry. Lymphatic spread was assessed by histopathological examination of lymph nodes (LN). A representative subset of 87 tumours was analysed by tissue microarray (TMA) to evaluate expression of markers that potentially influence haematogenous vs. lymphatic spread. Patients were followed up for a median of 54.7 months.ResultsOf the 177 patients, 114 (64%) were BM?/LN?, 38 (22%) BM?/LN+, 19 (11%) BM+/LN? and 6 (3%) BM+/LN+. Multivariate analysis of histopathological characteristics revealed that increasing tumour size was significantly associated with both LN positivity (p = 0.003) and BM positivity (p = 0.01), the presence of lymphovascular invasion significantly correlated with LN+ (p = 0.01), whereas lower histological grade was significantly associated with BM+ (p = 0.03). LN+ and BM+ were non-significantly negatively related to each other. Univariate analysis of the TMA data showed differential expression patterns for several factors; significant differences between effects on the two metastatic pathways (lymphatic vs. haematogenous) were found for expression of CD54 (p = 0.03), osteopontin (p = 0.04), bone sialoprotein (p = 0.04) and CXCR4 (p = 0.009). High expression of CD54, osteopontin and bone sialoprotein (BSP) was positively associated with BM + but was either not associated, or negatively associated, with LN+. High CXCR4 expression was positively associated with LN+ and negatively with BM+. High VEGF–C expression was associated with both LN+ and BM+, although this did not attain statistical significance. Due to the small number of clinical events during clinical follow-up, no associations were identified between metastatic spread patterns, recurrence and/or death.ConclusionThese findings suggest that distinct lymphatic and haematogenous metastatic pathways exist in early breast cancer and that these pathways are governed by specific biological markers.     

Breast cancer risk associated with CYP1A1 genetic polymorphisms in Japanese women

Although several reports are available on the association between CYP1A1 polymorphisms and breast cancer risk in Caucasian women, it has never been reported in Japanese women. Since breast cancer incidence and clinicopathologic features of breast cancers are different between Japanese and Caucasian women, it is conceivable that the risk factors of breast cancer might also differ. In addition, a preliminary study has shown that the frequencies of the variant allele in the CYP1A1 gene are different among ethnic groups. Therefore, in the present study, we investigated the association of CYP1A1 polymorphisms with breast cancer risk in Japanese women. The association of two CYP1A1 polymorphisms, that is, 3' noncoding region (6235(T/C)) and codon 462 (Ile/Val), with breast cancer risk was analyzed by a case-control study (195 cases and 272 controls). Variant allele 6235C carriers at the 3' noncoding region polymorphism showed a significantly ( p < 0.01) reduced breast cancer risk (odds ratio 0.60; 95% CI 0.41–0.88) as compared with noncarriers, and variant allele 462Val carriers at the codon 462 polymorphism also showed a significantly ( p < 0.05) reduced risk (odds ratio 0.66; 95% CI 0.45–0.96) as compared with noncarriers. The relationship between the genetic polymorphisms and clinicopathologic characteristics of breast cancers was also investigated. Variant allele 6235C carriers showed a significantly ( p < 0.02) higher positivity of lymph node metastasis than noncarriers (54% versus 36%), and tumors measuring less than 2 cm were significantly ( p < 0.03) more frequently observed in variant allele 462Val carriers than noncarriers (50% versus 33%). These results suggest that the CYP1A1 polymorphisms would be useful for predicting breast cancer risk as well as some tumor characteristics in Japanese women.     

Immunomagnetic quantification of circulating tumor cells in patients with urothelial cancer

Objectives: To evaluate the relationship between circulating tumor cells (CTC) and clinical parameters in metastatic urothelial cancer (UC). Methods: CTC were enumerated with the CellSearch System, which was developed using an EpCAM antibody‐based immunomagnetic capture and automated staining methodology. UC cell lines (RT4, T24, TCC, UMUC3 and 253J) and mixed blood from healthy males were analyzed. Blood samples from 16 patients without metastatic UC and 20 patients with metastatic UC were also analyzed. Results: The accuracy and reliability of the assay were determined using spiked UC cells (RT4 and T24), which showed a strong linear correlation (r = 0.99) and recovery rate of 94% ± 5% and 84% ± 6%, respectively. Three UC cell lines (TCC, UMUC3 and 253J) tested negative. The 16 patients without metastatic UC tested negative as well. Eleven (55%) patients with metastatic UC tested positive for at least one CTC. Seven (35%) had two or more CTC. Significantly more CTC were seen in patients with two or more sites of metastasis than those with one site of metastasis (P = 0.004). Conclusions: Based on these findings, CTC could represent a potential marker to monitor the response to chemotherapy in patients with metastatic UC.