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。     

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。     

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.     

Clinical features of hepatocellular carcinoma that occur after sustained virological response to interferon for chronic hepatitis C

Background and Aim: This study investigated the clinical features of hepatocellular carcinoma in patients with sustained virological response to interferon for hepatitis C viral (HCV) infection. Methods: A total of 7715 patients with HCV infection were treated with interferon and followed up for more than 1 year after withdrawal of interferon in 64 Japanese hospitals and clinics between July 1988 and August 2001. Sustained virological response was obtained in 2515 (32.6%) patients. Of these 2515 patients, clinical data were collected for 38 patients in whom hepatocellular carcinoma developed. Sustained virological response was defined as HCV RNA negativity more than 6 months after the termination of interferon. Results: All patients were HCV RNA negative at the time of diagnosis of hepatocellular carcinoma. The median period until the detection of hepatocellular carcinoma was 4.7 years (range 1.4–9.0 years). There were significant improvements in hepatic function including serum albumin, aspartate aminotransferase, alanine aminotransferase, indocyanine green test, platelet count and histological activity grade in comparison with those before interferon therapy and at the onset of hepatocellular carcinoma. The maximum tumor size in patients without medical follow‐up for 1 year or more (median: 60 mm) was significantly larger than in patients who were periodically followed up for 6 months or less (median: 25 mm) (P = 0.002). Conclusions: The present findings emphasize the importance of regular medical follow up of patients with HCV infection, as even patients showing a sustained virological response to interferon and in whom hepatic function has improved have the potential to develop hepatocellular carcinoma.     

Human hepatocellular carcinoma tumor xenografts

Castrated or sham-operated male athymic mice were inoculated with cells from the human hepatocellular carcinoma cell line PLC/PRF/5. There were no significant differences between the two groups with respect to the number of animals developing tumors, the time to tumor development, or the subsequent rate of increase in either tumor base area or mouse serum alpha-fetoprotein concentration. Androgen receptors were assayed in nuclei obtained from three separate liver cancer cell lines and from normal adult human liver. Similar concentrations, ranging from 235 to 550 fmol/mg DNA, of nuclear androgen receptors were detected in all tissues. Low percentages of androgen receptors were retained on DNA-cellulose. Although the presence of receptors implies the potential for metabolic effects of androgens in normal and malignant liver, our in vivostudies suggest that castration does not alter significantly the growth of liver cancer xenografts in athymic mice.     

43例口腔癌平阳霉素术前化疗效果相关因素分析

目的 :通过对平阳霉素术前化疗效果的相关因素分析 ,早期判断平阳霉素对口腔鳞癌的效果 ,为确定进一步治疗方案提供指导。方法 :对本院近 3年来接受平阳霉素 (总量为 80mg)化疗的 4 3例口腔癌患者进行直线相关和回归分析 ,观察化疗期间体温改变、发热持续时间、胃肠道反应时间及WBC改变与疗效的关系。结果 :①接受平阳霉素化疗有效的患者多在第 3～ 6天出现局部反应 ;②发热的程度及胃肠道反应与化疗效果密切相关 (P<0 .0 5 )。结论 :化疗早期出现的发热、胃肠道症状及局部反应可以作为早期判断预期疗效的方法。     

Aesthetic refinements in prophylactic mastectomy with immediate reconstruction

Immediate reconstruction of more than 1000 breasts was performed on high-risk patients on whom a prophylactic mastectomy was done. The mastectomy removes as much breast tissue as possible while leaving sufficient skin, and possibly the nipple-areola complex, to enable immediate reconstruction. The creation of symmetrical, well-balanced muscle pockets for the implant is the most important factor in producing satisfactory results in these cases.