应用自制微粒子活履炭指导胃癌淋巴结清除术

胃癌淋巴结转移是影响其预后最重要的因素之一。胃癌手术时彻底清除引流病灶的转移淋巴结而保留不引流病灶未发生转移的正常淋巴结,是所期望的术式。我们于胃癌术中在癌周所属淋巴结内注入自制微粒子活性炭下称自制炭,以黑染淋巴结为导向进行清除,减少了以往手术中在淋巴结清除上的盲1 材料与方法目性。1．1 病例选择 自1998年3月～1999年1月间我科共收治胃癌患者139例,行根治切除者98例。选其中68例,随机分成两组,实验组下称注墨组38例,对照组30例。以上两组病例根治度均为B级以上。病期、术式及淋巴结清除范围均无显著性…     

微颗粒活性炭在乳癌根治术中的应用

作者对１８例乳癌患者，于术前经癌灶周及癌灶中央注入吸附抗癌药物的微颗粒活性炭（ｍｍｃＣＨ４０）术中以ｍｍｃ－ＣＨ４０染黑的淋巴结作为清除的标志。结果表明：①术前经癌周及癌灶中央注墨，术中均可见到淋巴结广泛黑染；②癌周及癌中央注墨淋巴结的黑染率无差异；③经癌周注墨淋巴结黑染度为８７．９％，高于经癌中央注黑组的５９．７％；④注墨组黑染及未黑染的淋巴结转移度无显著差异；⑤注墨组平均每例清除３０个淋巴结，     

B超引导下胃壁穿刺注墨指导胃癌淋巴结清除术

作者采用Ｂ超引导下经皮胃壁穿刺注墨的方法，对２７例胃癌病人术前穿刺注墨，术中观察淋巴结墨染情况，作淋巴结清除术。并与同期３１例未穿刺注墨组作对照。结果显示：注墨组平均每例清除淋巴结３６个，转移率６７％，转移度１３％。对照组平均每例清除淋巴结２３个，转移率７１％，转移度１９％。其中ｎ３、ｎ４站淋巴结清除率，注墨组５９％，对照组２３％（Ｐ＜０．０１）。同内镜下胃壁穿刺注墨比较，Ｂ超引导下胃壁穿刺注墨具有指示准确、穿刺成功率高（８９％）、病人易接受等优点。     

纳米炭淋巴结示踪剂在腔镜食管癌根治术中的应用

目的:探讨纳米炭淋巴结示踪剂在腔镜食管癌根治术中的应用效果.方法:选行腔镜食管癌切除患者46例,按随机数字表法分为观察组和对照组,各23例.观察组术前2 h胃镜下注射纳米炭淋巴结示踪剂;对照组不给示踪剂,对比两组的淋巴结清扫数目、淋巴结黑染率及术后6个月内并发症.结果:观察组平均清扫淋巴结数、<5 mm淋巴结及其转移明显高于对照组;淋巴结清扫时间和平均最小淋巴结直径均明显低于对照组,差异具有统计学意义(P<0.05);观察组淋巴结黑染率明显高于对照组,且黑染淋巴结的转移度明显高于非黑染者(P<0.01);观察组术中出血量、术后引流量、喉返神经损伤发生率明显低于对照组(P<0.05).结论:纳米炭示踪剂在腔镜食管癌根治术中有助于淋巴检出、缩短检出时间、提高转移淋巴结检出度,以及小淋巴结的检出,降低术中喉返神经损伤.     

纳米炭在结直肠癌术中淋巴示踪的应用

[目的]探讨纳米炭淋巴示踪剂在结直肠癌手术中的应用价值。[方法]将55例结直肠癌患者随机分为实验组(26例)和对照组(29例)。实验组于术中在癌旁周缘分4～6点浆膜下注射纳米炭注射液1ml,术中参考黑染的淋巴结适当调整淋巴清扫范围,解剖标本,取出淋巴结并依据黑染与否、淋巴结位置及大小分组,送检病理检查。[结果]标本中可见淋巴结有广泛的不同程度的黑染,实验组平均每例检获的淋巴结数、淋巴结转移率、直径<3mm的淋巴结检出率等均显著高于对照组;区域外黑染淋巴结取出活检均呈阴性。[结论]术中应用纳米炭注射液能明显提高淋巴结检获的数量,最大可能地清除转移的淋巴结,指导病理分期,同时清扫范围外的黑染淋巴结均呈阴性,对结直肠癌过大范围的淋巴清扫提出疑问,因此对结直肠癌的淋巴清扫术有一定的指导意义。     

纳米炭在腹腔镜下进展期直肠癌根治术中的应用

  目的  评价纳米炭在腹腔镜下进展期直肠癌根治术中的临床应用价值。  方法  选取2010年12月至2012年3月唐山市人民医院胃肠外科接受腹腔镜下直肠癌根治术治疗的80例患者,根据术中是否应用纳米炭分为试验组（40例）和对照组（40例）,比较两组术中清扫淋巴结的总数,直径≤5 mm淋巴结数目及转移淋巴结数目,并观察有无药物不良反应。  结果  试验组注射纳米炭均未发生不良反应且术中黑染淋巴结清晰可辨;试验组患者清扫淋巴结总数[（25.5±8.78）枚vs.（16.05±4.84）枚],直径≤5 mm淋巴结枚数[（22.6±8.25）枚vs.（13.65±4.62）枚],转移淋巴结枚数[（3.13±4.14）枚vs.（1.35±2.06）枚]均显著高于对照组（P<0.05）;其中2例直肠癌患者术中发现肠系膜下动脉根部及髂内动脉旁有黑染淋巴结,相应扩大手术切除范围,术后病理证实淋巴结有肿瘤细胞转移。  结论  在腹腔镜下直肠癌根治术中,应用纳米炭对直肠癌淋巴结清扫有指导作用,方法安全、有效。      

染料引导下胃癌淋巴清除术的临床应用

目的:探讨纳米炭示踪胃癌前哨淋巴结的临床价值.方法:48例胃癌患者随机分为实验组(n=24)和对照组(n=24).实验组,术中注入纳米炭混悬液(CNP),标记后行胃癌根治术.对照组,未标记直接行胃癌根治术.结果:实验组原发灶平均直径为3.1 cm,黑染淋巴结22例(91.67％),共清除淋巴结673枚,平均每例28.04枚,第2、3站淋巴结清除数分别为305和182枚,平均12.71和7.58枚;对照组共清除淋巴结445枚,平均每例18.54枚,第2、3站淋巴结清除数分别为178和86枚,平均7.42和3.58枚.实验组和对照组淋巴结转移率分别为62.5％和33.3％,差异有统计学意义,P＜0.05.实验组清除的淋巴结中黑染度为58.10％(391/673).第1站为41.94％(78/186),第2和3站为61.97％(189/305)和68.13％(124/182),第1站与2和3站差异有统计学意义,x2 =37.85,P＜0.01.结论:胃癌根治术中应用纳米碳能增加淋巴结清除数目,使根治术更加彻底.     

开腹与腹腔镜直肠癌根治术临床对比研究

目的:对比研究腹腔镜与传统开腹直肠癌根治术在直肠癌治疗中的应用。方法:将2003年8月~2005年2月需行直肠癌根治术的患者根据其意愿分为腹腔镜组(28例)和传统开腹组(31例),对比两组手术安全性,术后恢复,肿瘤根治性和随访结果。结果:腹腔镜和开腹组均无手术死亡病例;腹腔镜组术中出血量明显少于开腹组,P=0·035;术后排气时间、下床时间、住院天数显著短于开腹组,P=0·041;两组生存时间、淋巴结清除数目,切口种植转移差异无统计学意义,P=0·065。结论:腹腔镜直肠癌根治术创伤小、恢复快、安全、有效,符合肿瘤根治原则。     

术中淋巴结示踪定位技术对进展期胃癌淋巴清扫指导作用的研究

目的探讨术中淋巴结示踪定位技术对进展期胃癌淋巴清扫的指导作用。方法术中肿瘤周围注射第三代淋巴结示踪剂——纳米炭混悬液,在D2根治术的基础上以黑染淋巴结为导向进行个体化清扫。统计清扫淋巴结的数目及淋巴结转移情况、黑染情况,并观察不良反应及并发症的发生。结果本组平均每例清扫淋巴结（35.1±13.4）枚,其中阳性淋巴结（6.9±2.5）枚;淋巴结黑染率为52.7%,黑染淋巴结中发生转移的阳性率（27.6%）,高于未黑染淋巴结（10.8%）,差异有统计学意义（χ2=6.034,P=0.016）;本组发生1例输入襻梗阻。结论进展期胃癌在D2根治术的基础上以术中淋巴显影技术为指导进行个体化清扫,能增加淋巴结清扫的彻底程度,并可提高清扫转移淋巴结的效率,但肿瘤进展程度会影响淋巴显影效果。     

纳米炭对乳腺癌腋窝淋巴结示踪效果及其安全性的初步研究

目的探讨国产纳米炭混悬液对腋窝淋巴结的示踪效果及其安全性。方法2008年5月至2009年9月间对21例乳腺癌患者在术前采用纳米炭进行淋巴结示踪。患者年龄30～65岁,平均45．3岁。术前24～72h于乳晕周围分4点皮下均匀注射纳米炭混悬液共1ml。手术方式采用改良根治术5例,腔镜下乳房皮下腺体切除、腋窝淋巴结清除加假体植入术12例,乳腺癌局部扩大切除加腔镜腋窝淋巴结清除术4例。术后观察腋窝淋巴结的黑染情况并送病理检查。结果21例患者分别检出淋巴结14～32枚,平均每例21．5枚,共452枚。肉眼下黑染淋巴结共435枚,黑染率为96．3％（435／452）,其中明显黑染率为85．4％（386／452）。腋窝淋巴结无转移6例,有转移15例。有转移的淋巴结共45枚,均为明显黑染淋巴结,转移淋巴结黑染率为100％。经病理证实,未黑染的淋巴结均未出现癌转移。所有患者经8个月至2年的随访,均未出现复发转移及明显肝肾功能异常。有纳米炭残留的局部组织在术后1年行活组织检查,见乳腺组织间隙有较多的纳米炭颗粒沉集,但未见明显的炎症反应或组织变性。结论纳米炭混悬液经乳晕周围皮下注射后24～72h行腋窝淋巴结清除可达到良好的淋巴结示踪效果,有效避免转移淋巴结的漏检。残留体内的纳米炭无明显的毒副反应。纳米炭是一种安全可靠的腋窝淋巴结示踪剂。     

Farnesyltransferase inhibitors: antineoplastic properties, mechanisms of action, and clinical prospects

Farnesyltransferase (FTase) inhibitors are among the current wave of molecularly targeted anti-cancer agents being used to attack malignancy in a rational manner. A large body of preclinical data indicates that FTase inhibitors block cancer cell proliferation through both cytostatic and cytotoxic effects. Interestingly, FTase inhibitors have rather limited effects on normal cell function, suggesting that they may target unique aspects of cancer cell pathophysiology. The development of FTase inhibitors was predicated on the discovery that the Ras oncoproteins must be post-translationally modified to transform cells. However, recent work indicates that the anti-neoplastic effects of FTase inhibitors depend on altering the post-translational modifications of non-Ras proteins as well. In particular, a critical target protein that responds to FTase inhibition by blocking tumor cell growth is RhoB, an endosomal Rho protein that functions in receptor trafficking. In this review, we survey the biological foundations for the clinical development of FTase inhibitors, and consider some of the latest mechanistic studies that reveal how these agents affect cellular physiology.     

Targeting tumor vasculature with homing peptides from phage display

Tumor vasculature expresses a number of molecular markers at much lower levels than those seen in the blood vessels of normal tissues, and in some cases, such markers are undetectable. The presence of these markers relates to angiogenesis; the same markers are shared by all blood vessels undergoing angiogenesis. The endothelial cells, pericytes and smooth muscle cells, and the vascular extracellular matrix in angiogenic vessels can each express such markers. Molecularly, they represent vascular growth factor receptors, cell adhesion proteins and their receptors. Screening of phage display libraries for peptides that home to tumor vasculature when injected into mice has recently provided a new tool for analyzing the distinguishing features of tumor vasculature. Tumor-homing peptides isolated in this manner, as well as an antibody against a form of fibronectin expressed in tumor blood vessels, have been found to serve as targeting devices to concentrate drugs and other therapeutic materials to tumors in in vivo models. Such a targeting strategy can therefore potentially improve the efficacy of drugs and reduce their side effects.     

Identification of EBV transforming genes by recombinant EBV technology

Epstein-Barr virus (EBV) is able to infect primary B-lymphocytes but usually does not proceed to replicate more virions. Instead, EBV persists as an incomplete virus and expresses 12 gene products that transform the growth of these cells into continuously proliferating lymphoblastoid cell lines. Because EBV is associated with several human malignancies, there is intense interest in delineating the molecular functions of these EBV gene products in transformation. This review focuses on the recombinant EBV technologies that have been developed to introduce specific mutations into EBV and test the functions of these EBV genes in primary B-lymphocyte growth transformation.     

Matrix metalloproteinases in tumor invasion and metastasis

Extensive work on the mechanisms of tumor invasion and metastasis has identified matrix metalloproteinases (MMPs) as key players in the events that underlie tumor dissemination. Studies using natural and synthetic MMP inhibitors, as well as tumor cells transfected with cDNAs encoding the MMPs characterized thus far have provided compelling evidence that MMP activity can induce or enhance tumor survival, invasion and metastasis. Because of the ability of MMPs to degrade extracellular matrix (ECM) proteins, the principal mechanism whereby MMPs promote tumor development has been thought to be the proteolytic breakdown of tissue barriers to invasion and the associated facilitation of circulating tumor cell extravasation. However, recent evidence stemming from the use of novel experimental approaches indicates that MMPs do not play a major role in the process of extravasation itself. Rather, they appear to promote intravasation (the process of penetrating the circulation following invasion of blood vessels) and regulate the relationship between tumor cells and host tissue stroma subsequent to extravasation. In addition, the discoveries that a growing number of proteolytically active MMPs may localize to the cell surface in association with adhesion receptors, and that MMP substrates include latent cytokines and growth factors, provide a new conceptual framework for the mechanisms whereby MMPs influence tumor behavior.     

New aspects of integrin signaling in cancer

Members of the integrin family of cell adhesion receptors influence several important aspects of cancer cell behavior, including motility and invasiveness, cell growth, and cell survival. Engagement of integrins with extracellular matrix (ECM) proteins can activate members of the Rho-family of small GTPases; conversely, Rho- and Ras-family proteins can influence the ability of integrins to bind their ligands. These events impinge on the control of cell motility, and ultimately on invasive and metastatic behavior. Integrin engagement with ECM also has important effects on cell survival, particularly for cells of epithelial origin. In some cases, specific integrins have selective effects on the efficiency of signal transduction in cell survival pathways.     

Role of LMP1 in immune control of EBV infection

The Epstein-Barr virus (EBV) encoded latent membrane protein (LMP1) plays a crucial role in the long-term persistence of this virus within the cells of the immune system. Not only is this protein critical for the transformation of resting B cells by EBV, it also displays pleiotropic effects on various cellular proteins expressed in the host cell. These include up-regulation of expression of B cell activation antigens, adhesion molecules and various components of the antigen processing pathway. Here we discuss how LMP1 acts like an expression 'switch' which, depending on the stage of EBV infection, manoeuvres various pathways that either modulate the immune system towards or against its survival.     

腹部压块对膈肌运动影响的研究

目的 :研究腹部压块对膈肌运动的影响。方法 :选择拟行立体适形放疗患有肺癌或肝脏肿瘤的患者 2 0例。按治疗体位仰卧于体部立体放疗定位负压袋内 ,待患者呼吸平稳后 ,将灯光野的中心点置于膈顶运动的最低点 ,在膈肌运动至最高位时拍摄照片 ,测量膈肌运动的最大幅度 ;然后 ,将心形腹部压块放置于患者剑突下 ,并用定位框架的腹带交叉固定 ,按压程度以不引起患者呼吸困难或其他不适为标准 ,5min后按上述方法再次测量膈肌运动的最大幅度。结果 :2 0例患者未加腹部压块的运动幅度为0 6 2～ 2 6 7cm ,平均 (1 4± 0 6 4)cm ,加腹部压块后的膈肌运动幅度为 0 2 8～ 2 0 8cm ,平均 (1 0±0 5 5 )cm ,加腹部压块后膈肌运动幅度平均减小 (0 4± 0 34)cm ,P =0 0 0 0。加腹部压块后 90 % (18/2 0 )的患者膈肌运动幅度受到不同程度的限制 ,但有 10 % (2 /2 0 )的患者膈肌运动幅度增加。结论 :腹部压块可使大部分患者膈肌运动的幅度减小 ,但少部分患者例外 ,即腹部压块并不能使所有膈肌周围肿瘤的照射容积减少。建议在制定放射治疗计划前应预先进行测量和评价     

ABCG2在肺癌中表达的定量研究

目的 观察ABCG2在肺癌和癌周肺组织的表达,从量化角度阐明其在肺癌组织中表达的病理学意义.方法 常规石蜡包埋、HE切片确诊,用免疫组化SP法检测ABCG2在肺癌和癌周肺组织的定位和表达,用LeicaQ500MC图像分析系统对其表达强度进行定量分析,并用表达的阳性单位(positive unit PU)反映其表达强度.结果 ABCG2蛋白在肺癌和癌周正常肺组织中的表达主要定位在细胞质和细胞膜.在癌周正常肺组织的支气管和细支气管上皮呈弥漫表达,腺上皮呈灶性表达;肺鳞癌和肺腺癌弥漫或大片表达,肺鳞癌表达的PU值高于肺腺癌(P＜0.001),肺大细胞癌和肺小细胞癌不表达,PU值接近于零.癌周肺组织表达的PU值高于各型肺癌(P＜0.05).ABCG2蛋白表达的PU值在肺癌原发灶和转移灶之间无差别(P＞0.05),且与肺癌患者的性别、年龄、转移和TNM分期未见明显相关性(P＞0.05),与肺癌分化程度有关(P＜0.001).分化程度越高,PU值越高,但高分化肺癌和癌周肺组织的表达PU值差异无显著性(P＞0.05).结论 ABCG2蛋白表达程度与肺癌类型及分化程度具有相关性,可能成为判断其指标之一.     

Telomerase and human tumorigenesis

Human cancer cells, unlike their normal counterparts, have shed the molecular restraints to limited cell growth and are immortal. Exactly how cancer cells manage this at the molecular level is beginning to be understood. Human cells must overcome two barriers to cellular proliferation. The first barrier, referred to as senescence, minimally involves the p53 and Rb tumor-suppressor pathways. Inactivation of these pathways results in some extension of lifespan. However, inactivation of these pathways is insufficient for immortalization. As normal cells undergo repeated rounds of DNA replication, their telomeres shorten due to the inability of traditional DNA polymerases to completely replicate the end of the chromosomal DNA. This shortening continues until the cells reach a second proliferative block referred to as crisis, which is characterized by chromosomal instability, end-to-end fusions, and cell death. Stabilization of the telomeric DNA through either telomerase activation or the activation of the alternative mechanism of telomere maintenance (ALT) is essential if the cells are to survive and proliferate indefinitely. Conversely, loss of telomere stabilization by an already-immortalized cell results in loss of immortality and cell death. Together this indicates that telomere maintenance is a critical component of immortality. In this review we attempt to describe our current understanding of the role of telomere maintenance in senescence, crisis, and tumorigenesis.     

Post-translational regulation of COX2 activity by FYN in prostate cancer cells

While increased COX2 expression and prostaglandin levels are elevated in human cancers, the mechanisms of COX2 regulation at the post-translational level are unknown. Initial observation that COX2 forms adduct with non-receptor tyrosine kinase FYN, prompted us to study FYN-mediated post-translational regulation of COX2. We found that FYN increased COX2 activity in prostate cancer cells DU145, independent of changes in COX2 or COX1 protein expression levels. We report that FYN phosphorylates human COX2 on Tyr 446, and while corresponding phospho-mimetic COX2 mutation promotes COX2 activity, the phosphorylation blocking mutation prevents FYN-mediated increase in COX2 activity.