结直肠癌根治术患者术后辅助化疗依从性的影响因素分析

目的 探讨结直肠癌根治术患者术后辅助化疗依从性的影响因素.方法 收集130例结直肠癌根治术患者的病历资料,分析患者术后辅助化疗依从性的影响因素.结果 客观性影响因素的单因素分析结果显示,不同年龄、性别、术后并发症、体重指数(BMI)、体表面积(BSA)结直肠癌根治术患者术后辅助化疗依从性比较,差异均有统计学意义(P﹤0.05);不同肿瘤位置、病理类型结直肠癌根治术患者术后辅助化疗依从性比较,差异均无统计学意义(P﹥0.05).进一步行多因素Logistic回归分析,结果显示,年龄≥65岁、女性、术后出现并发症、BMI﹤22 kg/m2、BSA﹤1.6 m2是影响结直肠癌根治术患者术后辅助化疗依从性的客观性独立危险因素(P﹤0.05).主观性影响因素的单因素分析结果显示,不同对生命的态度、家庭经济情况、病情保密、家庭支持、不良反应结直肠癌根治术患者术后辅助化疗依从性比较,差异均有统计学意义(P﹤0.05);就医困难结直肠癌根治术患者术后辅助化疗依从性比较,差异无统计学意义(P﹥0.05).进一步行多因素Logistic回归分析,结果显示,对生命绝望、家庭经济困难、不对病情保密、无家庭支持、无法耐受不良反应是影响术后辅助化疗依从性的主观性独立危险因素(P﹤0.05).接受化疗患者病死率为2.78％(2/72),低于拒绝化疗患者的12.07％(7/58),差异有统计学意义(χ2=4.303,P=0.038).结论 结直肠癌根治术患者术后辅助化疗依从性的主观性及客观性影响因素较多,临床医护人员可根据具体的影响因素采取有效的干预措施,从而提高患者术后辅助化疗治疗依从性,改善患者预后.     

C-肽及胰岛素抵抗水平与结直肠癌发病风险的相关性研究

目的 探讨C-肽及胰岛素抵抗(insulin resistance,IR)与结直肠癌发病的相关性.方法 选取结直肠癌患者(n=50)、结直肠腺瘤患者(n=27)以及经过肠镜检查正常的对照组者(n=36),共113例,应用统计学分析比较其空腹血清胰岛素(FINS)、C-肽、空腹血糖水平以及胰岛素抵抗指数的差异.结果 结直肠癌组患者空腹血清胰岛素、胰岛素抵抗指数、C-肽、空腹血糖均高于对照组,差异有统计学意义(0＜0.01).结直肠腺瘤组患者C-肽和空腹血糖高于对照组,差异有统计学意义(P＜ 0.05).多因素Logistic回归分析发现年龄、C-肽、空腹血糖与结直肠癌发病有关;C-肽、胰岛素抵抗与结直肠息肉发病有关.结论 C-肽及胰岛素抵抗与结直肠息肉、结直肠癌发病相关.     

结直肠癌合并息肉92例临床分析

[目的]探讨结直肠癌合并息肉的诊断和处理.[方法]对1993年12月至2003年12月结直肠癌合并结直肠息肉病人92例,占14.3%(92/625).术前行纤维结肠镜检查同时处理结直肠息肉者18例(19.5%),切除结直肠癌同时处理息肉者50例(54.3%),术后二期处理息肉者24例(26.2%),其中8例在术后早期(6周内)处理,16例在6周～5年内处理.[结果]67例获得随访,其中术前、术中、术后早期(6周内)获得随访51例,息肉复发4例,无恶变,术后6周后二期处理息肉,获得随访16例中,12例息肉明显增大,其中恶变3例(18.8%).[结论]结直肠合并息肉发病率高,并且息肉有明显恶变倾向,因此尽可能在术前或术中明确诊断,力争在术前、术中、术后早期(6周内)处理息肉,术后应加强随访及时发现和处理复发息肉.     

Vasohibin-1、PD-1、SDF-1在结直肠癌患者中的表达及其与临床特征的关系

目的 探讨Vasohibin-1、程序性死亡受体1(PD-1)、基质细胞衍生因子-1(SDF-1)在结直肠癌患者中的表达及其与临床特征的关系.方法 选取200例结直肠癌患者(结直肠癌组)和200例结直肠息肉患者(结直肠息肉组),比较两组患者Vasohibin-1、PD-1、SDF-1的表达情况及其与直肠癌患者临床特征的关系.采用Logistic回归分析法分析影响结直肠癌患者Vasohibin-1、PD-1、SDF-1表达情况的因素.结果 结直肠癌组患者的Vaso-hibin-1、PD-1、SDF-1阳性表达率均明显高于结直肠息肉组,差异均有统计学意义(P﹤0.01).有淋巴结转移、组织学分型为黏液腺癌、Ⅲ～Ⅳ期、肿瘤直径≥5 cm结直肠癌患者的Vasohibin-1、PD-1、SDF-1阳性表达率明显高于无淋巴结转移、组织学分型为管状腺癌、Ⅰ～Ⅱ期、肿瘤直径﹤5 cm的患者,差异均有统计学意义(P﹤0.01);不同年龄、性别、肿瘤部位结直肠癌患者的Vasohibin-1、PD-1、SDF-1阳性表达率比较,差异均无统计学意义(P﹥0.05).Logistic回归分析结果表明,淋巴结转移和TNM分期是影响结直肠癌患者Vasohibin-1、PD-1、SDF-1阳性表达的独立因素(P﹤0.05).结论 结直肠癌患者的Vasohibin-1、PD-1、SDF-1阳性表达率较高,且与淋巴结转移和TNM分期密切相关.     

腹腔镜联合内镜治疗105例结直肠肿瘤的疗效分析

目的 探讨腹腔镜联合内镜治疗结直肠肿瘤的疗效及安全性.方法 选取105例结直肠癌患者,按住院单双号分为2组,观察组(53例)行腹腔镜联合结肠镜切除手术,对照组(52例)行腹腔镜切除手术.观察并记录患者围手术期指标、近期疗效及随访2年期间并发症发生情况,以评价腹腔镜联合内镜治疗结直肠癌的疗效及安全性.结果 2组在术后镇痛时间上相比,差异没有统计学意义(P＞0.05).观察组患者手术时间、术中失血量、住院时间均明显少于对照组(p＜0.05);术后2组在下床时间、排气时间、排便时间上相比,差异没有统计学意义(P＞0.05).随访2牟期间,观察组并发症共计5例,对照组9例,2组并发症发生率相比,差异没有统计学意义(P＞0.05).结论 腹腔镜联合结肠镜手术,既可弥补腹腔镜手术时术者手触觉功能的丧失,又能弥补结肠镜手术时视觉功能的不足,明确肿瘤切除范围,缩短手术时间,减少术中出血量,患者恢复快,并且具有一定安全性.     

NOB1在结直肠癌中的表达及其临床意义

目的：研究NOB1编码蛋白在结直肠癌及正常结直肠黏膜（距癌组织边缘5cm以上）、结直肠良性息肉中的表达特征.探讨结直肠癌中NOB1表达的临床病理意义.方法：利用免疫组织化学SABC法检测87例结直肠癌组织、22例正常结直肠黏膜组织18例结直肠息肉组织中NOB1的表达.结果：NOB1在结直肠癌,结直肠良性息肉及正常结直肠黏膜中的阳性表达率分别为74.7％、44.4％、13.6％,三组进行比较,差异有统计学意义（P＜0.01）.细胞分化差的结直肠癌NOB1蛋白阳性率表达高（P＜0.05）与患者年龄,性别,肿瘤浸润深度及淋巴结转移无明显相关性.结论：NOB1蛋白在结直肠癌中表达升高,并与大肠癌临床病理学特征有关.     

腹腔镜下结直肠癌根治术危险因素及并发症分析

目的 探讨腹腔镜下结直肠癌根治术的危险因素以及疗效.方法 收集腹腔镜下行结直肠癌根治本的患者102例,并选取40例常规开腹手术患者作为对照组,对比分析影响其手术的危险因素以及患者近远期并发症情况.结果 对腹腔镜下结直肠癌术后并发症危险因素行Logistic回归分析发现,患者的TNM分期、伴发心肺疾患、肝肾功能不全以及术中出血量≥100 ml为其独立危险因素.对比分析两组手术方式患者近远期并发症,差异不具统计学意义(P＞0.05).腹腔镜组患者与对照组相比,两者在手术时间、术中出血量、术后首次排气时间、术后进食时间以及住院时间上差异显著,具有统计学意义(P＜0.05).两者在淋巴结清扫个数上差异不具统计学意义(P＞0.05).结论 腹腔镜值得广泛应用于结直肠癌的治疗中.     

Gal-3和MUC1蛋白在结直肠癌中的表达及与预后的关系

目的 检测MUC1和Gal-3蛋白在结直肠癌中的表达,探讨与结直肠癌临床病理特征及预后的关系.方法 应用免疫组织化学SP法检测MUC1和Gal-3蛋白在81例结直肠癌组织中的表达,另取癌旁正常组织20例及结直肠腺瘤组织20例作为对照组,并结合临床病理特征及随访资料分析临床意义.结果 结直肠癌中MUC1和Gal-3蛋白的表达明显高于癌旁组织和结直肠腺瘤组织(P＜0.05).MUC1和Gal-3蛋白的表达与结直肠癌的浸润、TNM分期、淋巴结转移有关,与患者的性别、年龄、肿瘤部位、肿瘤大小、分化程度和组织学类型均无明显关系(均P＞0.05).两者表达呈正相关(r=0.84,P＜0.05);MUC1、Gal-3蛋白阳性表达的患者5年生存率低于阴性表达者(P＜0.05).结论 MUC1和Gal-3与结直肠癌的发生、发展及生存期相关,联合检测可能对结直肠癌的诊断、治疗及预后评价具有一定的临床意义.     

LDH-A乙酰化在结直肠腺癌组织中的表达及意义

目的 探讨乳酸脱氢酶A(LDH-A)的乙酰化在结直肠腺癌组织中的表达及其与结直肠腺癌患者临床特征的关系.方法 应用免疫组织化学染色法检测40例结直肠腺癌患者的结直肠腺癌组织及其相应的40例癌旁正常组织中乙酰化LDH-A的表达情况.结果 结直肠腺癌组织中乙酰化LDH-A蛋白的阳性表达率为22.5％(9/40),低于癌旁正常组织的47.5％(19/40),差异有统计学意义(P﹤0.05).Ⅰ～Ⅱ期结直肠腺癌组织中乙酰化LDH-A蛋白的阳性表达率高于Ⅲ～Ⅳ期的结直肠腺癌组织,差异有统计学意义(P﹤0.05).不同年龄、性别、分化程度结直肠腺癌患者的结直肠腺癌组织中乙酰化LDH-A蛋白的阳性表达率比较,差异均无统计学意义(P﹥0.05).结论 LDH-A乙酰化水平在结直肠癌组织中呈低表达,提示其与结直肠癌的发生可能具有一定的关系,在结直肠癌发展中,LDH-A乙酰化可能起到负性调节的重要作用.     

结直肠息肉内镜下特点及治疗

背景与目的:结直肠痛是常见的肿瘤,近年来发病率呈上升趋势.多数结直肠癌起源于腺瘤性息肉,而息肉的发现和切除可降低结直肠癌的发病率.为此,我们探讨不同年龄组的结直肠息肉的临床和内镜特点以及内镜下治疗情况.方法:2009年1月-2010年1月在复旦大学附属肿瘤医院内镜科接受肠镜检查的患者5 152例,按年龄分为中青年组(＜60岁)和老年组(≥60岁).比较分析两组资料结直肠息肉的肠镜下特点和病理类型,以及内镜下息肉治疗情况.结果:老年组的结直肠息肉检出率和息肉癌变率(37.65%,11.18%)均高于中青年组(19.8%,7.43%),差异均有统计学意义(P=0.000).两组的息肉好发于直肠和乙状结肠(30.53%,29.62%;29.78%,25.29%),均以腺瘤性息肉为多(61.19%,36.99%);而数目多、广基≥2 cm以及病理为绒毛状腺瘤的息肉,癌变率较高.除息肉癌变和巨大息肉外,两组资料中80%以上息肉予肠镜下治疗(80.8%,91.3%)全部顺利完成,未有严重并发症发生.结论:结肠镜检查是发现并处理息肉的有效手段,腺瘤性息肉的形态、大小、数目和病理以及患者的年龄与腺瘤性息肉的恶变有一定关系;结直肠息肉应尽可能内镜下治疗,并定期随访,减少结直肠癌的发生.     

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.     

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.     

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     

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.