膀胱移行细胞癌树突状细胞浸润和PCNA表达的临床病理研究

目的　探讨膀胱移行细胞癌组织中树突状细胞 (DCs)浸润和PCNA的表达与临床病理特征的关系。方法　采用免疫组织化学SP法检测 3 1例膀胱移行细胞癌术后组织标本中增殖细胞核抗原 (PCNA )以及DCs标志蛋白S 10 0的表达。结果　不同病理分级及临床分期以及单发癌灶与多发癌灶的膀胱移行细胞癌 ,其DCs数量相互比较 ,均有显著性差异 (P <0 .0 5 ) ;原发与复发膀胱癌的DCs浸润数无显著性差异 (P >0 .0 5 )。不同病理分级膀胱移行细胞癌PCNA阳性表达细胞数比较有显著性差异 (P<0 .0 5 )。结论　膀胱癌DCs浸润数量随病理分级、临床分级的升高而降低 ,而PCNA随病理分级的升高而增高。DC可以作为预测膀胱癌生物行为的指标之一     

Survivin及Caspase-3在浅表性膀胱移行细胞癌中表达及预后意义

目的:探讨凋亡相关蛋白Survivin及Caspase-3在浅表性膀胱移行细胞癌表达及其临床意义.方法: 应用S-P免疫组织化学法检测47例行TUR-BT术切除膀胱移行细胞癌标本组织石蜡切片中Survivin和Caspase-3表达的情况,结合临床资料进行分析.所有标本均经病理证实为T1期内.10例正常膀胱黏膜为对照.结果: Survivin在膀胱移行细胞癌标本中的表达阳性率为68.1%(32/47),而正常对照组中无一例呈阳性表达;Caspase-3在膀胱移行细胞癌标本中表达阳性率为38.3%(18/47),与对照组阳性率90%(9/10)相比差异有统计学意义(P<0.05).Survivin表达与膀胱移行细胞癌的组织学分级、初发和复发显著相关(P<0.05),但与肿瘤数目无关;Caspase-3表达与膀胱移行细胞癌的初发复发相关,但与组织学分级、肿瘤数目无关.相关性分析表明,膀胱移行细胞癌中Survivin表达与Caspase-3表达呈负相关. 结论: Survivin在膀胱癌组织中选择性表达与膀胱移行细胞癌的分化程度密切相关,Caspase-3蛋白在膀胱移行细胞癌中表达下降,Survivin及Caspase-3蛋白对于判断膀胱移行细胞癌预后有重要临床指导意义.     

尿核基质蛋白22和细胞角蛋白18在膀胱移行细胞癌中的表达及其临床意义

目的 探讨尿核基质蛋白22(NMP22)和细胞角蛋白18(CK18)在膀胱移行细胞癌中的表达及其临床意义.方法 采用酶联免疫吸附法(ELISA)对293例膀胱移行细胞癌、400例非移行细胞肿瘤、105例泌尿系良性病患者进行尿NMP22和CK18蛋白水平的检测.结果 膀胱移行细胞癌患者术前NMP22和CK18表达中位值分别为17.3 U/ml和484.2 U/L,非移行细胞肿瘤患者分别为6.8 U/ml和156.0 U/L,良性疾病患者分别为2.3 U/ml和66.6 U/L,3组之间进行比较,差异有统计学意义(P<0.001).以NMP22 10 U/ml和CK18 120 U/L为界值,其对膀胱移行细胞癌诊断的敏感度分别为79.2%和78.2%,特异度分别为88.6%和82.9%,两者联合检测的敏感度为91.7%.对术后患者动态观察,治疗有效患者的NMP22和CK18表达水平较治疗前明显下降,而复发、转移的患者则上升,差异有统计学意义(P<0.01).NMP22和CK18对膀胱移行细胞癌的检测有显著的相关性(r=0.689 P<0.0001).NMP22和CK18表达水平在不同病理分级和不同分期的患者中比较,差异有统计学意义(均P<0.01).结论 尿NMP22和CK18检测可作为膀胱移行细胞癌术前诊断、病情监测重要指标,两者联合检测可进一步提高敏感度.     

血管内皮生长因子在膀胱移行细胞癌中表达的意义

目的:探讨膀胱移行细胞癌中血管内皮生长因子(VEGF)的表达及其与临床病理指标的关系.方法:应用免疫组织化学方法,对62例原发性膀胱移行细胞癌及8例正常膀胱组织中VEGF进行检测.结果:正常膀胱移行上皮均为阴性反应,膀胱癌组织中VEGF阳性表达率为56.5%.低分化和浸润性癌中VEGF阳性表达率明显高于高分化和表浅性癌组(P<0.05),复发者阳性表达率明显高于未复发者(P<0.05),WEGF阳性表达者3年生存率明显低于阴性表达者(P<0.05).结论:VEGF表达对膀胱癌生物学行为有重要影响,VEGF表达有可能成为预测膀胱癌复发、转移和预后的一种指标.     

膀胱移行细胞癌组织中cyclinD1和CDK4的表达及其与临床病理的关系

目的　研究膀胱移行细胞癌组织中cyclinD1和CDK 4的表达及其与临床病理变化的关系。方法　采用免疫组化方法对 8例正常膀胱和 69例膀胱移行细胞癌组织中cyclinD1和CDK 4的表达进行观察。 结果　膀胱移行细胞癌组织中cyclinD1的表达高于正常膀胱组织 (P <0 .0 5 )。cyclinD1表达阳性者的肿瘤细胞分化较差 ,术后易复发 ,生存时间较短 ;而CDK 4的阳性表达仅与患者术后复发有关 (P <0 .0 5 ) ,与病理分级和生存时间无关 (P >0 .0 5 )。结论　cyclinD1的表达可作为判断膀胱细胞癌病理分级 ,术后复发和临床预后的指标 ,而CDK 4只能作为术后复发的参考指标。     

凋亡相关蛋白Survivin及Fas在膀胱移行细胞癌中的表达及其临床意义

目的探讨凋亡相关蛋白Survivin及Fas在膀胱移形细胞癌表达及其临床意义。方法应用S-P免疫组织化学法检测45例膀胱移行细胞癌及10例正常膀胱黏膜组织石蜡切片中Survivin和Fas表达的情况,结合临床资料进行分析。结果Survivin在膀胱移形细胞癌标本中的表达阳性率为68.9%(31/45),而正常对照组中无一例呈阳性表达;Fas在膀胱移行细胞癌标本中的表达阳性率为46.7%(21/45),与对照组阳性率100.0%(10/10)相比,差异有显著性(P<0.05)。Survivin的表达与膀胱移行细胞癌的组织学分级、初发和复发显著相关(P<0.05),但与临床病理分期、肿瘤数目无关;Fas的表达与膀胱移行细胞癌的组织学分级、肿瘤数目、初发和复发相关,但与临床分期无关。相关性分析表明,膀胱移行细胞癌中survivin的表达与Fas表达呈负相关。结论Survivin在膀胱癌组织中选择性表达与膀胱移行细胞癌的分化程度密切相关,Fas蛋白在膀胱移行细胞癌中表达下降,survivin及Fas蛋白对于判断膀胱移行细胞癌预后有重要临床指导意义。     

尿中血管内皮生长因子表达与膀胱移行细胞癌诊断及术后监测

目的探讨尿中血管内皮生长因子(VEGF)表达与膀胱移行细胞癌的关系,以及尿VEGF做为瘤标的价值.方法用抗体夹心ELISA法测量58例研究对象的尿VEGF,并与尿细胞学检查比较(双盲法).其中28例为膀胱移行细胞癌,每3个月随访1次,6例复发.结果尿VEGF在膀胱癌组高于非膀胱癌组(P＜0.001);G1级癌分别低于G2、G3级癌(P＜0.05),在早期复发组高于未复发组(术前)(P＜0.05),尿VEGF诊断实验的特异度和灵敏度分别为93.3%、85.7%.结论尿VEGF水平可反映膀胱癌的预后、复发;尿VEGF做为诊断和术后监测瘤标有较高价值,优于尿细胞学检查.     

α-2b干扰素加顺铂预防膀胱癌术后复发的远期疗效

目的观察α-2b干扰素联合顺铂膀胱粘膜下注射及术后膀胱灌注对预防膀胱移行细胞癌复发的远期临床疗效.方法106例诊断为膀胱移行细胞癌的病人,随机分为两组.A组56例,采用术前60～90min行膀胱内灌注顺铂50mg,术中用α-2b干扰素300万U加顺铂30mg,生理盐水稀释60ml～80ml行瘤体周围粘膜下广泛注射,并于术后应用两药联合灌注(α-2b干扰素300万U+顺铂50mg).B组50例仅用顺铂,方法和剂量同A组.结果101例获得随访5～10年,平均7年.A组和B组存活率分别为73.5%(36/53)和67.4%(31/48),差异无显著性(P＞0.05).但复发率和无瘤存活率分别为26.5%(13/53)和62.3%(33/53)及45.8%和41.7%(20/48),两组差异均有显著性(P＜0.05).结论α-2b干扰素加顺铂粘膜下注射及术后灌注可有效的预防膀胱移行细胞癌术后复发,降低复发率、延迟复发时间,效果优于单用顺铂或干扰素,两药联合有相加和合成作用.     

E—cadherin和α—catenin在膀胱移行细胞癌中的表达及意义

[目的]研究钙粘附分子（E-cadherin,E-cad)和α-连接蛋白在膀胱移行细胞癌中的表达及其临床意义。[方法]正常膀胱粘膜E-cad呈正常表达，96例膀胱移行细胞癌中E-cad及α-cat的异常表达率分别为44.8%（43/96）和58.3%(56/96)。两者之间具有显著相关性。E-cad及α-cat的异常表达率与肿瘤的病理分级、临床分期、复发及生存率显著相关。[结论]E-cad及α-cat的异常表达在膀胱移行细胞癌的恶性进展过程中起重要作用。可作为判断肿瘤恶性程度及复发预后的分子生物学指标。     

膀胱癌PCNA蛋白表达及其与复发的关系

[目的]探讨增殖细胞核抗原（proliferating cell nuclear antigen,PCNA）蛋白在膀胱癌中的表达情况,并分析其与临床病理特征及复发的关系。[方法]148例膀胱移行细胞癌患者标本,25例癌旁正常组织标本作为对照,采用免疫组化SP法检测PCNA蛋白的表达。[结果]癌旁正常组织中PCNA蛋白的阳性表达水平明显低于肿瘤组织（16.0%vs50.7%,P〈0.001）。PCNA蛋白的表达与膀胱癌的分级、分期、复发有关（P〈0.05）,与患者的年龄、性别、肿瘤数目及肿瘤大小无关（P〉0.05）。本组104例浅表性膀胱癌（Ta～T1）随访2～95个月,其中复发64例,复发组与未复发组PCNA蛋白的阳性表达率分别为56.3%和15.0%（P=0.001）。[结论]PCNA蛋白在膀胱癌中高表达,其高表达提示预后不良。     

Prognostic Significance of Inflammation-associated Blood Cell Markers in Nonmetastatic Clear Cell Renal Cell Carcinoma

ObjectivesOur objective was to evaluate the effect of the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), and red blood cell distribution width (RDW) on the survival outcomes of nonmetastatic clear cell renal cell carcinoma (ccRCC).Materials and MethodsWe accessed our single-center, urologic-oncologic registry to extract the data for patients who had undergone nephrectomy for nonmetastatic ccRCC. The optimal cutoff for these markers was determined using X-tile software, and survival analyses using Cox regression were performed.ResultsA total of 687 patients had undergone nephrectomy. The optimal cutoffs for NLR, PLR, LMR, and RDW were 3.3, 210, 2.4, and 14.3%, respectively. The NLR, PLR, LMR, and RDW were significantly associated with a larger pathologic tumor size, and stage, more aggressive Fuhrman grade, and the presence of tumor necrosis. After adjusting for age, baseline Eastern Cooperative Oncology Group, pathologic tumor and nodal stage, and Fuhrman grade, only PLR remained an independent prognostic marker for both cancer-specific survival (hazard ratio, 2.69; 95% confidence interval, 1.36-5.33; P = .004) and overall survival (hazard ratio, 2.19; 95% confidence interval, 1.36-3.50; P = .001). When the PLR was included with the Leibovich score and University of California, Los Angeles, integrated staging system, the Harrell’s c-index increased from 0.854 to 0.876 and 0.751 to 0.810, respectively, for cancer-specific survival at 5 years after nephrectomy. When risk stratified by the Leibovich risk group and UCLA integrated staging system, PLR was a significant prognostic factor only within the intermediate- to high-risk groups.ConclusionsPLR is a robust prognostic marker in nonmetastatic ccRCC that clearly outperforms other inflammatory indexes in those who had undergone nephrectomy. However, its prognostic effect was limited in the low-risk category of ccRCC.     

Inhibition of Glioma Cell Proliferation by Neural Stem Cell Factor

Summary Neural stem cells (NSC) have unique differentiation-, proliferation-, and motility properties. To investigate whether they secrete factors that interfere with the proliferation of glioma cells, we grew glioma cells in conditioned medium (CM) obtained from cultures of neurospheres including neural stem / progenitor cells (NSPC) isolated from embryonic (E14)- or adult mouse brain or fetal human brain. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and BrdU-labeling assays showed that CM from NSPC (NSPC/CM) contained factor(s) that inhibited the proliferation of glioma cells by 28–87%. Filter-fractionation of NSPC/CM revealed that the 50,000–100,000 nominal molecular weight limit (NMWL) fraction contained the inhibitory activity. On the basis of these observations we transplanted 203G glioma cells and/or NSPC into the intrathecal space of the cisterna magna of mice to investigate whether NSPC interfere with the proliferation of glioma cells in vivo. Mice transplanted with both 203G and NSPC survived significantly longer than did mice transplanted only with 203G. We concluded that NSPC secrete factor(s) that may control glioma cell proliferation.     

High Occurrence of Non-Clear Cell Renal Cell Carcinoma in Oman

It is conventionally accepted that renal cell carcinoma (RCC) occurs in older patients and the clear cell type is the most common histology. However, ethnic variations exist and this study was carried out to determine the epidemiological pattern of RCC in Oman. Ninety RCC patients who presented to a tertiary care center in the Sultanate of Oman from 2010 to 2014 were studied. The main findings were that the median age of presentation was low, more patients presented with localized stage, and there was a higher incidence of non-clear (especially papillary) histology. Data from other Gulf countries and possible reasons for the different profile are discussed.     

Inhibition of Natural Killer Cell Cytotoxicity by Cell Growth-related Molecules

Certain MHC class I molecules on target cells are known to inhibit the cytotoxic action of NK cells. By using monoclonal antibody (mAb) Cho-1, we have found inhibitory non-MHC class I cell surface molecules that are noncovalently-associated with 200 kDa and 40 kDa antigens. Poly I-C-induced rat NK cells were not cytotoxic to rat fetus-derived fibroblast WFB cell line. In contrast, NK cells were cytotoxic to H- ras oncogene-induced transformants of WFB, W14 and W31. FACS analysis indicated that mAb Cho-1 reacts with WFB, but not with W14 and W31 cells. Thus, this antigen may disappear concomitantly with cell growth and transformation. Cho-1 antigens were also expressed on other NK-resistant lines, such as mouse BALB3T3 fibroblast, EL-4 lymphoma and human fibroblast HEPM. However, they were not expressed on NK-sensitive mouse YAC-1 and H- ras transformant (Brash) of BALB3T3 cells. Furthermore, treatment of target cells with IFN-γ clearly induced the cell surface expression of Cho-1 antigens, and conferred a resistance to NK cytolysis on target cells. These data strongly suggest that Cho-I antigen expression may correlate with target cell susceptibility to NK cells. Indeed, treatment of NK-resistant WFB as well as HEPM cells with F(ab')₂ fragments of mAb Cho-1 resulted in the acquisition of susceptibility to NK cytolysis. Cho-1 antigens may be novel molecules that regulate the NK resistance of cells.     

人干扰素对HL60,K562细胞生长及细胞周期的影响

用人干扰素(α和γ)与HL60、K562细胞共同培养后,对细胞生长有不同程度抑制作用。IFN_r对细胞生长抑制作用强于IFN_r,IFN_r和IFN_r联合应用有协同作用,在K562细胞,细胞在细胞周期中的分布也发生改变,G_0/G_1期细胞比例减少,S期细胞比例增高,在HL60细胞则无明显的细胞周期再分布情况。提示细胞在S期的堆积是细胞生长受抑的原因之一。     

Cell kinetics

Cell kinetic concepts have pervaded radiation therapy since the early part of the 20th century and have been instrumental in the development of modern radiotherapy. In this review, the fundamental radiobiological concepts that have been developed based on cell kinetic knowledge will be revisited and discussed in the context of contemporary radiation therapy. This will include how the proliferation characteristics, variation in sensitivity during the cell cycle and the extent of radiation-induced cell cycle delay translate into a variable time for the expression of damage, how cell kinetics interacts with hypoxia and how the response to fractionated radiation schedules is influenced by cell kinetics in terms of repair, redistribution, reoxygenation and repopulation. The promise of combining radiation with new biologically targeted agents and the potential of non-invasive positron emission tomography imaging of proliferation are areas where cell kinetics will continue to influence radiotherapy practice.     

Expressions of Cell Cycle Regulators in Human Colorectal Cancer Cell Lines

To study the altered mechanisms of cell cycle regulation in colorectal cancer, the expressions of cyclins, cyclin-dependent kinases (CDKs), CDK inhibitors, p53 and retinoblastoma (Rb) protein were analyzed by western blotting in a series of human colorectal cancer cell lines. The colorectal cancer cell lines exhibited various expression patterns of cell cycle regulators, which may reflect differences in the biological characteristics of cancer cells and in the genetic backgrounds of carcinogenesis. A correlation was found between p53 gene alteration and p21 expression, suggesting that p53 gene mutation usually suppresses p21 expression, though p21 expression could be induced via both ap53 -dependent and a p53 -independent pathway in colorectal cancer. None of the cell lines studied expressed p16 protein, suggesting that inactivation of p16 may be a common alteration in colorectal cancer. Moreover, all the D-type cyclins, especially D2 and D3, were expressed at a high level in most of the cell lines. Loss of p16 expression and increased expression of D-type cyclins promote CDK-mediated Rb phosphorylation. All of the colorectal cancer cell lines studied herein expressed Rb protein, but the growth-suppressive properties of Rb may be inactivated by the loss of p16 expression and increased expressions of D-type cyclins. In view of the pivotal role of Rb in cell cycle regulation, loss of p16 expression and overexpression of D-type cyclins may be critical alterations in colorectal cancer.