蛋白质组学及其在前列腺癌研究中的应用

随着蛋白质组学技术的发展,越来越多的肿瘤标记物被发现,并逐渐应用于临床,这将为肿瘤的早期诊断和预后监测提供可靠的依据。现综述蛋白质组学的研究策略及其在前列腺癌研究中的应用。     

低位直肠癌保留神经的腹膜外侧方扩大清扫的效果分析

目的 探讨低位直肠癌保留神经的腹膜外侧方扩大清扫对患者术后生存率、排尿功能和性功能的影响。方法 回顾性分析我院1996年1月至2000年6月期间收治的392例进展期低位直肠癌实施保留神经的根治性切除术患者的临床资料，其中行腹腔内清扫173例，腹腔内加腹膜外侧方清扫219例，2组患者在年龄、性别、浸润肠壁深度及肿瘤病理组织学类型方面差异无统计学意义。结果 腹腔内加腹膜外侧方清扫组侧方淋巴结转移率为17．8％（39／219），侧方盆壁非连续性癌灶转移率为5，9％（13／219）。术后发生排尿功能障碍：腹腔内清扫组7例（4．0％），腹腔内加腹膜外侧方清扫组113例（51．6％），2组比较差异有统计学意义（P〈0．01）；性功能障碍：腹腔内清扫组93例男性患者中有12例（12．9％），腹腔内加腹膜外侧方清扫组119例男性患者中有62例（52．1％），2组比较差异有统计学意义（P〈0．01）；局部复发率：腹腔内清扫组为16．2％（28／173），腹腔内加腹膜外侧方清扫组为9．6％（21／219），2组比较差异有统计学意义（P〈0．05）；5年生存率：腹腔内清扫组为49．1％（85／173），腹腔内加腹膜外侧方清扫组为59．4％（130／219），2组比较差异有统计学意义（P〈0．05）。结论 低位直肠癌保留神经的腹膜外侧方扩大清扫，可以减少局部复发，提高患者5年生存率，但也会影响患者术后排尿和男性性机能。     

Survivin在食管癌中的表达及其与bcl-2表达关系的相关研究

目的探讨Survivin在食管癌组织中的表达及其与bcl-2蛋白表达的相关性。方法应用免疫组织化学SP法,检测Survivin、bcl-2蛋白在68例食管癌组织和20例正常食管组织中的表达。结果Survivin蛋白在正常食管组织中低表达或不表达,68例食管癌组织中,49例表达阳性,占72.1%。Survivin蛋白表达与分化程度、淋巴结转移密切相关(P<0.05)。食管癌组织bcl-2蛋白表达阳性、阴性组中,Survivin蛋白阳性表达率分别为94.7%(36/38)和43.3%(13/30),两者比较,差异有统计学意义(P<0.05)。Survivin蛋白表达与bcl-2蛋白表达密切相关。结论Survivin在食管癌组织中表达上调,通过抑制细胞凋亡,在食管癌的发生中起到重要作用;凋亡相关基因bcl-2的上调与Survivin的表达可能在食管癌变中起协同作用。     

原发性肾上腺皮质癌的诊治分析

目的总结和提高原发性肾上腺皮质癌的诊治水平。方法回顾分析16例肾上腺皮质癌患者的临床资料。根据其临床症状、内分泌功能测定、影像学特点做出诊断，手术治疗并随访。结果16例患者中，内分泌功能紊乱者8例，以库欣征、性征异常、醛固酮增多症为主。超声、CT、MRI测定肿瘤直径为4．8～19．5cm，平均7．8cm。3例有远处转移。行根治性切除术13例，侵及同侧肾脏者做肾和肾上腙切除术2例，肾上腺肿瘤并腔静脉癌栓切除2例，腔静脉部分切除1例。病理结果：Ⅰ其耳2例，Ⅱ期8例，Ⅲ期3例，Ⅳ期3例。随访3-62个月，手术2年以上的11例患者中有6例仍存活，但1例肺转移，1例骨转移；死亡5例，平均存活26个月。结论肾上腺皮质癌患者预后差。影像学检查结合临床症状是早期诊断的关键，根治性手术是惟一有效的治疗方法。     

PTEN及Bcl-2蛋白在膀胱移行细胞癌中的表达及其意义

目的：探讨PTEN及Bcl-2蛋白在膀胱移行细胞癌的表达规律及其临床意义。方法：应用免疫组织化学链亲和素-生物素-霉复合物（SP）方法检测43例膀胱移行细胞癌和7例正常黏膜组织中PTEN及Bcl-2蛋白的表达．分析二者的表达与膀胱癌病理参数的关系。结果：（1）G1、G2、G3肿瘤PTEN表达阳性率分别为85．7％、80．4％、73．3％，浸润性肿瘤和表浅性肿瘤表达阳性率分别为70．4％和93．8％，说明PTEN表达阳性率与肿瘤病理分级、临床分期有关。（2）G。、G2、G3肿瘤Bcl-2表达阳性率分别为14．2％、57．14％、66．67％，浸润性肿瘤和表浅性肿瘤表达阳性率分别为59．3％和43．8％，说明Bcl-2表达阳性率与肿瘤病理分级、临床分期有关。（3）随着肿瘤恶性程度的增高和临床分期进展，PTEN蛋白阳性率呈下降，Bcl-2表达呈增高趋势，二者表达呈负相关关系。结论：PTEN的抑癌作用可能与Bcl-2有关．二者的异常表达在膀胱移行细胞癌的发生、发展过程中起重要作用。二者同时检测有助于判断预后。     

脑膜癌病的临床与病理特点

目的探讨脑膜癌病的临床与病理特点。方法回顾性分析142例脑膜癌病患者的临床及脑脊液(CSF)细胞学资料和免疫细胞化学标记结果。结果本组患者临床特点:头痛123例(86.62%),头晕19例(13.38%),发热26例(18.31%),视物模糊10例(7.04%)。CSF检查及免疫标记:全部患者CSF中均发现癌细胞;癌细胞上皮膜抗原(EMA)( ),细胞角蛋白(CK)( ),CD14(-),胶质纤维酸性蛋白(GFAP)(-)。其中99例(69.72%)CK低分子( )、高分子(-),诊断为转移性腺癌;33例(23.24%)CK高分子( )、CK低分子(-),诊断为转移性鳞癌;10例(7.04%)CK高分子( )、CK低分子( ),考虑为腺鳞癌。105例找到原发灶,其中67例(47.18%)确诊为肺癌;23例(16.20%)在消化道内找到原发灶;9例(6.34%)为乳腺癌;子宫内膜癌、卵巢癌、肝癌各1例。另有37例(26.06%)未找到原发灶。诊断明确的患者中,15例失访,另90例中有82例(91.11%)于确诊后3～14个月死亡。未找到原发灶的患者中,有6例失访,另31例中有28例(90.32%)在确诊后2～13个月内死亡。结论脑膜癌病患者以头痛、头晕为主要临床表现,并可伴有发热及视物模糊。CSF细胞学检查是诊断脑膜癌病的主要依据,通过免疫细胞化学的方法,可以确定转移癌细胞。脑膜癌病患者预后较差。     

经直肠超声引导13点前列腺系统穿刺活检术的并发症及防治

目的探讨经直肠超声引导13点前列腺系统穿刺活检术的并发症及防治措施.方法回顾性分析本组1998年8月至2004年12月336例接受经直肠超声引导13点前列腺穿刺活检术患者的临床资料.结果336例患者中出现的并发症有:血尿218例;血便67例,血精10例,感染10例,明显疼痛(VAS评分大于5分)85例,血管迷走神经反应10例等.结论经直肠超声引导13点前列腺系统穿刺活检术用于诊断前列腺癌常可见小的并发症,大的并发症则很少见.该术式用于诊断前列腺是安全的.     

X chromosomal and autosomal loss of heterozygosity and microsatellite instability in human cervical carcinoma

The study analyzes tumor material and normal tissue from 27 patients with pure squamous cell carcinoma of the uterine cervix for loss of heterozygosity (LOH) and microsatellite instability (MSI) on 14 autosomal and 11 X chromosomal loci. Overall, 4-40% of the informative cases showed LOH at autosomal regions with the highest frequency at 3p (21-40%) and a marked frequency at 2q35-q37.1 (12.5%) and 17p13.3 (10%), representing regions with putative tumor suppressor gene (TSG) function. The frequency of X chromosomal LOH ranged from 4% to 20%, with a maximum at Xq28 (20%) and Xq11.2-q12 (17%), again indicating alterations in TSG. A 12% LOH was seen at Xq21.33-q22.3, a region encoding a protein with a regulatory function in the cell cycle via cyclin-dependent kinases. MSI was detected in autosomal regions in up to 7% in regions linked to the X chromosome in up to 11%, probably indicating alterations of mismatch repair mechanisms. Our results and those obtained from the literature suggest that autosomal LOH and MSI in carcinomas of the cervix uteri are predominantly found at regions with putative TSG function. Beside TSG alterations, X chromosomal LOH is probably more strongly connected to disturbances in cell cycle regulation.     

Statistical analysis of pathologic risk factors for intramyometrial lymphvascular space involvement in myoinvasive endometrial carcinoma

In a retrospective study using univariate analysis, we identified tumor type (nonendometrioid vs endometrioid), depth of myoinvasion (MI), mode of MI (infiltrative vs cohesive), and direct anatomic invasion of the cervical wall from the isthmus as significant positive risk factors for intramyometrial lymphvascular space involvement (LVSI). On multivariate analysis, tumor grade, depth of MI, and mode of MI retained their significance. We created a grid for the relative risks of LVSI with respect to these variables individually or in combination. We suggest that our indirect estimate of the risk of LVSI can help in assessing prognosis and determining the need for adjuvant therapy whenever LVSI is important in clinical decision making, but its pathologic diagnosis is uncertain.     

1,25(OH)2Vitamin D3 induces elevated expression of the cell cycle inhibitor p18 in a squamous cell carcinoma cell line of the head and neck

BACKGROUND: 1Alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2) Vitamin D(3)] induces growth inhibition in squamous cell carcinoma (SCC) cell lines of the head and neck by arresting the cells in the G0/G1 phase of the cell cycle, probably due to an enhanced expression of p21, which could be demonstrated in other cell lines (JPPA, SCC9) before. In SCC25, a SCC cell line isolated from tongue, growth inhibition but no overexpression of p21 was detected. The retinoblastoma gene, as a direct target of G1 cyclin-CDK complexes, showed an obvious shift from the hyperphosphorylated to the hypophosphorylated form under 1,25(OH)(2)Vitamin D(3), which indicates that the growth inhibition takes place in the G0/G1 phase. To explore the possible pathway of growth inhibition in SCC25 we investigated other cell cycle inhibitors (p18, p19, p27). METHODS: Synchronized cells were treated with 1,25(OH)(2)Vitamin D(3) over 96 h. The cell cycle status and expression of cell cycle-regulating proteins was determined by fluorescence-activated cell sorting (FACS) and Western blotting. An overexpression of p18 in 1,25(OH)(2)Vitamin D(3) vs. ethanol-treated cells was determined until 30 h in SCC25. No influence was detectable on the expression of p27 and p19. CONCLUSION: One mechanism by which 1,25(OH)(2)Vitamin D(3) controls cell growth might be the upregulation of p21. As p21 was unsusceptible to 1,25(OH)(2)Vitamin D(3) in SCC25, other inhibiting proteins were necessary to be tested. The proven upregulation of p18 seems to be the responsible step for growth inhibition of 1,25(OH)(2)Vitamin D(3) in SCC25.