Twist、E-cadherin和β-catenin在肝细胞肝癌中的表达及其与预后的关系*

目的:探讨Twist、E-cadherin 和β-catenin 在肝细胞肝癌复发与转移中的作用及与预后的相关性。方法:以石蜡包埋组织切片,免疫组化SP法染色分别检测97例肝细胞肝癌,其中复发与转移组49例,非复发与转移组48例Twist、E-cadherin 和β-catenin 的表达情况。结果:复发、转移与性别、年龄无关（P=0.424,P=0.738）,与临床分期密切相关（P=0.000）。 复发与转移组Twist、β-catenin 表达高于无复发与转移组（P=0.000;P=0.000）,复发与转移组E-cadherin 表达低于无复发与转移组（P=0.027）。Twist,β-catenin 阳性组平均生存时间分别为（28.880 ± 3.285）、（ 31.477 ± 3.359）个月,中位生存时间分别为26、28个月,阴性组平均生存时间分别为（44.603 ± 3.521）、（ 42.009 ± 3.720）个月,中位生存时间分别49、45个月,Twist、β-catenin 阳性组生存期较阴性组缩短差别具有统计学意义（P=0.002,P=0.029）。 E-cadherin 阳性组平均生存时间为（44.514 ± 3.447）个月,中位生存时间为49个月,阴性组为（29.110 ± 3.581）个月,中位生存时间为25个月,E-cadherin 阳性组生存时间较阴性组延长有统计学意义（P=0.002）。 结论:Twist、β–catenin 过度表达,E-cadherin 表达缺失可能与HCC 复发转移、不良生存预后存在相关性。      

胰腺癌组织S100A4和MMP-9表达及其预后意义的探讨

目的:探讨钙离子结合蛋白A4(S100A4)和基质金属蛋白酶9(MMP-9)基因在胰腺癌组织中的表达和临床病理因素及预后的关系。方法:采用免疫组化二步法检测63例手术切除的原发性胰腺癌组织中S100A4和MMP-9的表达情况,比较S100A4和MMP-9蛋白表达与临床病理因素的关系及对预后的影响。结果:63例胰腺癌标本中S100A4和MMP-9阳性率分别为74.6%(47/63)和68.3%(43/63)。S100A4和MMP-9蛋白过表达存在显著相关性,P=0.000。S100A4和MMP-9表达均与TNM分期、淋巴结转移和远处转移显著相关,同时MMP-9的表达也与肿瘤的大小及分化程度存在显著相关。S100A4阴性/MMP-9阴性患者(13例)中位生存时间(23个月)明显大于S100A4阳性/MMP-9阳性患者(36例)中位生存时间(9个月),χ2=15.353,P=0.000。分化程度(P=0.000)、淋巴结转移(P=0.003)和S100A4过表达(P=0.001)及MMP-9过表达(P=0.001)为影响预后的独立因素。结论:S100A4和MMP-9的高表达与临床病理参数密切相关两者在胰腺癌的生长浸润过程中起重要作用,可以作为判断预后的指标之一。     

腋淋巴结阳性乳腺癌结外侵犯的临床意义

目的 探讨乳腺癌患者淋巴结外侵犯(ECE)的临床意义.方法 回顾性分析1230例腋窝淋巴结阳性乳腺癌,观察ECE与临床病理指标之间关系及对患者预后的影响.结果 腋窝淋巴结阳性乳腺癌患者中,ECE阳性率为39.5%.绝经前和绝经后患者ECE的发生率分别为35.5%和47.5%(P＜0.001).ECE阳性组和阴性组的肿瘤直径分别为5.11±2.53 cm和3.90±1.80 cm(P＜0.001),肿瘤直径越大,ECE阳性比例越高(P＜0.001).ECE阳性患者和ECE阴性患者的阳性淋巴结数目分别为16.96±12.16和5.24±6.60(P＜0.001),随腋窝阳性淋巴结数目增多,ECE阳性率明显增加(P＜0.001).ECE的发生与ER、PR状态无显著相关(P=0.706).ECE足乳腺癌患者局部或区域复发的危险因素(P＜0.001),复发时间差异无统计学意义(P=0.559).ECE阳性组和ECE阴性组的远处转移时问分别为30.0个月和37.5个月(P=0.006).首发骨、皮肤和远隔淋巴结组及内脏转移组的ECE阳性率分别为60.4%和42.0%(P=0.001).ECE阳性患者的无转移生存时间、无局部或区域复发生存时间及总生存时间均小于ECE阴性患者.预后单因素和多因素分析显示,ECE是影响乳腺癌患者无转移生存时间、无局部或区域复发生存时间及总生存时间的独立危险因素.结论 乳腺癌患者ECE的发生与肿瘤直径和受累淋巴结数日呈正相关;ECE是乳腺癌局部或区域复发和远处转移的危险因素;ECE是影响乳腺癌患者无转移生存时间、无局部或区域复发生存时间及总生存时间的危险因素.     

乳腺癌组织中转化生长因子β1的表达及其介导乳腺癌侵袭和转移的机制

目的 探讨转化生长因子β1(TGF-β1)蛋白和mRNA在乳腺痛组织中的表达,及其与明胶酶和明胶酶抑制物的关系.方法 建它组织芯片平台,应用免疫组化SP法检测160例乳腺痛组织TGF-β1、基质金属蛋白酶(MMP)-2、MMP-9、组织金属蛋白酶抑制物(TIMP)-1和TIMP-2蛋白的表达;应用原位分子杂交方法检测乳腺癌组织中TGF-β1 mRNA的表达.结果 160例乳腺癌TGF-β1、MMP-2、MMP-9、TIMP-1和TIMP-2蛋白表达的阳性率分别为73.7%、96.9%、95.0%、87.5%和89.4%,TGF-β1 mRNA表达的阳性率为56.2%.TGF-β1的蛋白表达与腋窝淋巴结转移、TNM分期和c-erbB-2表达有关(P＜0.05,P＜0.05和P＜0.01),TGF-β1的mRNA表达与腋窝淋巴结转移有关(P＜0.05).TGF-β1蛋白表达阳性组中位总生存期(OS)为60个月,中位无复发生存期(RFS)为59个月;TGF-β1蛋白表达阴性组中位OS为61个月,中位RFS为61个月,两组生存率差异无统计学意义(P=0.090),无复发生存率有统计学意义(P=0.023).TGF-β1的蛋白表达与MMP-2和MMP-9的表达均呈正相关(r=0.170,P＜0.05;r=0.221,P＜0.01).结论 TGF-β1的表达与乳腺癌侵袭和转移密切相关,TGF-β1的蛋白产物通过调控MMP-2和MMP-9促进乳腺癌的侵袭和转移.     

β-catenin和Nanog表达与结肠癌术后复发转移的相关性分析

目的:探讨结肠癌组织中β-catenin和Nanog表达及其对复发转移的预测作用.方法:采用免疫组化方法检测80例结肠癌组织β-catenin和nanog表达,RT-PCR检测20例冷冻标本肿瘤及癌旁组织中Nanog表达.结果:在80例患者中,35例出现复发转移,β-catenin和Nanog在转移组中表达率分别为65.7％(23/35)和60.0％(21/35),在非转移组中分别为31.1％(14/45)和26.7％(12/45),差异有统计学意义(x2=9.483,P=0.002;x2 =9.026,P=0.003).结肠癌原发灶分化程度不同,β-catenin和Nanog表达存在差异,但是同T和N分期没有明显联系.生存分析结果显示,不同表达状态其远处转移出现时间差异有统计学意义(P=0.000 2),两者均为阳性表达其转移率明显高于均为阴性表达.RT-PCR分析下结果显示,20例肿瘤组织中Nanog阳性表达率为35.0％(7/20),明显高于癌旁组织,P=0.018.结论:肿瘤组织中β-catenin和Nanog表达同结肠癌术后复发转移发生相关,两者联合检测有助于评估肿瘤转移的可能.     

肝细胞肝癌组织中Bcl-2核表达及MMP-2和MMP-9表达与术后复发转移及预后的关系

  目的  探讨抗凋亡蛋白Bcl-2、基质金属蛋白酶-2(MMP-2)和MMP-9在肝细胞肝癌中表达的关联性, 及其与复发、转移和预后的关系。  方法  以石蜡包埋组织切片, 免疫组织化学SP法染色检测97例肝细胞肝癌, 分别在复发与转移组49例和非复发与转移组48例中分析Bc1-2核表达和MMP-2、MMP-9表达的情况。  结果  复发与转移组Bcl-2核表达高于无复发与转移组(x2=7.912, P=0.005), 复发转移组MMP-9表达高于无复发转移组(x2=6.545, P=0.011), Bcl-2核表达阳性细胞率与MMP-9阳性细胞率存在相关性, 而与MMP-2无关Bcl-2核表达组患者生存时间较短, 差异具有统计学意义。  结论  Bcl-2核表达阳性患者更易出现复发与转移, 且与MMP-9过度表达存在关联性, 表明Bcl-2入核可能对肿瘤转移的相关生物学功能具有调节作用, 可作为评价HCC复发与转移、不良生存预后的候选临床标志。      

食管鳞癌患者外周血MMP-9 mRNA表达水平及临床意义研究

[目的]探讨食管鳞癌患者外周血中基质金属蛋白酶-9 (MMP-9)基因的表达及其与临床病理资料、生存情况的关系.[方法]应用实时定量PCR技术定量检测食管癌外周血标本中MMP-9 mRNA的表达,分析MMP-9基因表达情况与患者临床病理参数及预后之间的关系.[结果]在169例食管鳞癌患者外周血标本中,有106例(62.7％)存在外周血MMP-9基因的阳性表达,与食管癌的淋巴结转移(P=0.039)、远处转移(P=0.019)和TNM分期(P=0.014)显著相关.单因素生存分析显示N分期(P=0.000)、M分期(P=0.002)、TNM分期(P=0.003)、MMP-9表达(P=0.042)对患者生存的影响有统计学意义.MMP-9基因阳性表达的食管癌患者远期生存明显低于阴性表达者.多因素分析显示N分期是食管鳞癌患者预后的独立影响因子(RR=1.671,95％CI:1.212～2.306).[结论]食管鳞癌患者外周血中MMP-9基因的高表达与食管癌转移存在关联,并可提示食管癌患者的不良预后.     

TTF-1和SPA表达对早期肺腺癌术后复发预测及预后的判断价值

目的 研究术后肺腺癌患者组织中TTF-1和SPA的蛋白表达对其复发的预测价值及预后的影响.方法 收集行手术切除的Ⅰ～Ⅲ期肺腺癌患者112例,采用免疫组化方法检测组织中TTF-1以及SPA的表达.结果 68例患者出现复发,TTF-1阳性和阴性表达患者中位DFS分别为41个月和9个月(P =0.013),中位OS分别为65.0和23.0个月(P=0.037),SPA阳性与阴性表达患者中位DFS分别为59.0个月和15.0个月(P=0.018),中位OS分别为68.0个月和35.0个月(P =0.058).结论 早期肺腺癌术后组织中TTF-1和SPA的表达是其复发的有效预测指标,TTF-1阳性表达预后更好.     

结肠癌患者血清中miR-30a、miR-106b的表达及其临床意义

目的:探讨结肠癌患者血清miR-30a、miR-106b的表达及其在结肠癌进展及预测患者预后中的价值。方法:选取2012年06月至2013年02月本院收治的接受结肠癌手术治疗的患者80例为研究对象,20例同期健康人群作为对照组。逆转录 PCR法检测外周血血清中 miR-30a、miR-106b的表达水平,分析患者血清miR-30a、miR-106b表达与结肠癌临床病理及预后的关系。Spearman分析miR-30a、miR-106b表达的相关性。采用多因素logistic回归模型对结肠癌患者的预后影响因素进行分析,采用Kaplan-Meier生存分析miR-30a低表达组、miR-30a高表达组,miR-106b低表达组、miR-106b高表达组患者中位生存时间。结果:结肠癌患者血清miR-30a表达水平（1.03±0.02）低于正常人群（5.15±0.06）,差异具有统计学意义（t=16.38,P=0.01）;结肠癌患者血清miR-106b表达水平（2.62±0.35）高于正常人群（1.15±0.06）,差异具有统计学意义（t=10.17,P=0.03）。miR-30a、miR-106b表达与患者的组织分化类型、浆膜侵犯、淋巴结转移、远处转移、TNM分期有显著相关性(P＜0.05)。多因素logistic回归模型对结肠癌患者预后影响因素进行分析,TNM分期（Ⅲ+Ⅳ）、miR-106b高表达及miR-30a低表达是结肠癌患者预后不良的危险因素。miR-30a低表达组患者总体生存时间（55.3±4.1）个月低于miR-30a高表达组（76.4±2.4）个月（P=0.000）;miR-106b低表达组患者的总体生存时间（75.1±7.3）个月高于miR-106b高表达组（51.8±3.1）个月（P=0.000）。结论:miR-30a在结肠癌患者血清中低表达,miR-106b在结肠癌患者血清中高表达,二者的表达与肿瘤的进展、预后不良有关。     

89例乳腺癌脑转移患者的预后生存分析

目的探讨乳腺癌脑转移患者预后生存的影响因素。方法回顾分析1999年1月至2009年12月中国医学科学院肿瘤医院收治的89例乳腺癌脑转移患者的临床资料,其中HER-2阳性患者24例,HER-2阴性患者65例,分析ER、PR、TNM分期、淋巴结转移状态、Karnofsky评分、病情进展、脑转移情况、治疗措施等因素对乳腺癌脑转移生存期的影响。结果全组患者平均年龄49.0岁(23~74岁),确诊脑转移后中位生存期8.6个月(0.2~61.5个月)。单因素分析显示,乳腺癌脑转移患者HER-2表达阳性者与阴性者1年生存率分别为12.5%和46.2%(P=0.003),中位生存期分别为6.3个月和10.9个月(P=0.003);Karnofsky评分≥60分患者和<60分患者比较,1年生存率分别为43.5%和15.0%(P=0.017),中位生存期分别为10.1个月和5.3个月(P=0.019);非综合治疗组与综合治疗组1年生存率分别为21.6%和48.1%(P=0.014),中位生存期分别为6.0和13.6个月(P=0.006);内分泌治疗组与未采用内分泌治疗组1年生存率分别为66.7%和32.5%(P=0.027),中位生存期分别为29.3个月和8.5个月(P=0.003)。Cox多因素分析提示,HER-2表达状态、Karnofsky评分及是否综合治疗影响患者生存及预后。结论 HER-2表达状态、Karnofsky评分及脑转移后是否综合治疗是影响乳腺癌脑转移生存预后的因素,综合治疗有助于改善预后,延长生存。     

Etoposide, dexamethasone, cytarabine, and cisplatin in vincristine, doxorubicin, and dexamethasone-refractory myeloma

Based on remarkable activity in refractory lymphomas, a combination of etoposide, cisplatin (both administered by 4-day continuous infusions), cytarabine (Ara-C), and dexamethasone (EDAP) was evaluated in 20 patients with advanced myeloma refractory to standard melphalan and prednisone (MP) and/or vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and dexamethasone (VAD) and even to high doses of melphalan (HDM) (seven patients). Forty percent of patients responded regardless of previously recognized risk factors (eg, duration of drug resistance, tumor mass, and serum lactic dehydrogenase [LDH] level). While the median survival was only 4.5 months, patients with good performance (Zubrod less than 2) and low or intermediate tumor stage survived more than 14 months compared with only 2 months for the remaining group. EDAP could be readily administered in the outpatient clinic, but neutropenic fever prompted hospital admission in 80% of patients, half of whom developed penumonia and sepsis, a fatal outcome in four patients. Severe myelosuppression was of short duration, so that subsequent cycles could be administered every 3 to 4 weeks. No serious extramedullary toxicity, including renal toxicity, was encountered. Marrow toxicity and hence infectious complications may be reduced by elimination of Ara-C without compromising treatment efficacy. We conclude that the lack of cross-resistance with VAD and even HDM makes EDAP or a similar combination an attractive regiment to be formally explored in an alternating sequence with VAD in high-risk myeloma.     

Stress,coping, and hope

Hope is discussed in many literatures and from many perspectives. In this essay hope is discussed from the vantage of psychology and stress and coping theory. Hope and psychological stress share a number of formal properties: both are contextual, meaning‐based, and dynamic, and both affect well‐being in difficult circumstances. Two assumptions underlie this essay: (1) hope is essential for people who are coping with serious and prolonged psychological stress; and (2) hope is not a perpetually self‐renewing resource; it has peaks and valleys and is at times absent altogether. The relationship between hope and coping is dynamic and reciprocal; each in turn supports and is supported by the other. This relationship is illustrated with two adaptive tasks common across situations that threaten physical or psychological well‐being—managing uncertainty and coping with a changing reality. The essay describes ways in which coping fosters hope when it is at low ebb as well as ways in which hope fosters and sustains coping over the long term. Copyright © 2010 John Wiley & Sons, Ltd.     

Myelodysplastic syndromes, aging, and age: correlations, common mechanisms, and clinical implications

Myelodysplastic syndromes (MDS) are a heterogenous group of myeloid neoplasms that develop primarily in elderly patients. Although a specific molecular basis for the predominant incidence of MDS in higher age groups remains unknown, several lines of evidence suggest that the biology of aging and the pathogenesis of MDS share several genetic, epigenetic, and molecular features. The current review attempts to delineate these common aspects as well as additional discriminative features that are specific for MDS and thus help explaining disease-evolution and progression. In addition, the present review discusses age as an important prognostic factor and co-variable to be considered in treatment algorithms in MDS.     

Appendectomy,tonsillectomy, and neoplasia

Reports in the literature that study the frequency of cancer in individuals who have had their tonsils or appendix or both removed are reviewed. Some investigators found a high incidence of solid cancers—in particular, breast and colon neoplasms—in female patients who have had appendectomy, but others disagreed. The association of tonsillectomy and/or appendectomy with the later development of malignant lymphomas is not proven.     

Premenopausal intakes of vitamins A, C, and E, folate, and carotenoids, and risk of breast cancer.

Intakes of vitamins A, C, and E, folate, and carotenoids have been hypothesized to reduce the risk of breast cancer. However, previous epidemiological studies on these nutrients and breast cancer risk have been inconclusive, and have included primarily postmenopausal women. We examined the intake of these nutrients in relation to breast cancer risk among 90,655 premenopausal women ages 26-46 years in 1991 in the Nurses' Health Study II. Nutrient intake was assessed with a validated food-frequency questionnaire at baseline in 1991 and in 1995. During 8 years of follow-up from 1991 to 1999, we documented 714 incident cases of invasive breast cancer. Overall, none of the vitamins and carotenoids was strongly related to a reduced risk of breast cancer. However, intake of vitamin A, including preformed vitamin A and carotenoids, was associated with a reduced risk of breast cancer among smokers; participants in the highest quintile of total vitamin A intake had a multivariate relative risk of 0.28 (95% confidence interval 0.12-0.62; P, test for trend <0.001; P, test for interaction <0.001) compared with those in the lowest quintile of intake. We found no evidence that higher intakes of vitamins C and E, and folate in early adult life reduce risk of breast cancer. However, intake of vitamin A may be related to a reduced risk of breast cancer among smokers.