非小细胞肺癌患者血清CEA及CYFRA21-1水平动态分析

目的:探讨治疗前后不同时期非小细胞肺癌患者血清CEA、CYFRA21蛳1水平的变化规律及临床意义。方法:分别于化疗前、后采集非小细胞肺癌患者血清样本,采用放射免疫分析法检测患者血清CEA,CYFRA21蛳1含量,并对检测结果进行比较分析。结果:非小细胞肺癌患者CEA阳性率为59.2 %,其中鳞癌47.6 %,腺癌72.9 %。CYFRA21蛳1阳性率为65.1 %,其中鳞癌71.9 %,腺癌57.1 %。二者均随临床TNM分期增加而升高,手术后及化疗有效者CEA、CYFRA21蛳1逐渐降低。结论:动态检测患者CEA,CYFRA21蛳1水平对非小细胞肺癌的诊断、病程及转移情况、疗效及预后判断、监测复发有重要意义。     

卵巢癌细胞DNA倍体、p21及p53基因表达产物定量分析

目的　探讨卵巢癌DNA倍体、p2 1及 p5 3基因定量表达情况及其临床意义。 方法　应用流式细胞术 (FCM )和荧光免疫技术 ,对 3 9例卵巢癌组织的卵巢癌细胞和 9例正常卵巢组织的卵巢细胞的染色体倍体、p2 1基因和 p5 3基因表达产物进行定量分析。结果　在卵巢癌组织中DNA的异倍体率、p2 1、p5 3基因蛋白产物的阳性表达率均明显高于对照组 ,两者比较均有非常显著性差异 (P <0 .0 1)。结论　应用FCM定量测定卵巢癌细胞中的DNA倍体、p2 1及 p5 3基因表达产物 ,在临床上具有重要的参考价值     

P21WAF1, P27KIP1, TP53 and C-MYC analysis in 204 ovarian carcinomas treated with platinum-based regimens.

BACKGROUND: The prognostic and predictive value of cell cycle regulatory proteins in ovarian cancer has not been established. We evaluated the clinical and biological significance of P21(WAF1), P27(KIP1), C-MYC, TP53 and Ki67 expressions in ovarian cancer patients. MATERIALS AND METHODS: Immunohistochemical analysis was performed on 204 ovarian carcinomas of International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IV treated with platinum-based chemotherapy. Multivariate analysis with Cox and logistic regression models was performed in the whole group, and in the TP53-negative and TP53-positive subgroups. RESULTS: High P21(WAF1) labeling index (LI) was an independent positive predictor of platinum-sensitive response (P = 0.02). Overall survival was positively influenced by P21(WAF1) LI (P = 0.02) or by P21(WAF1) plus P27(KIP1) LI (P = 0.004) in the TP53-negative group only. Ki67 LI showed borderline association with disease-free survival (P = 0.05). Growth fraction was negatively associated with P21(WAF1) and P27(KIP1) indices in the TP53-negative group (P = 0.023 and 0.008, respectively), and these associations were borderline or lost in the TP53-positive group. Endometrioid and clear cell carcinomas differed from other carcinomas by having a low incidence of TP53 accumulation, a high incidence of C-MYC overexpression (70%) and a low median Ki67 LI (all with P <0.001). CONCLUSIONS: We have shown an independent predictive value of P21(WAF1) LI in ovarian carcinoma patients. The prognostic value of P21(WAF1) and P21(WAF1) plus P27(KIP1) LI was determined by TP53 status. A high frequency of C-MYC overexpression in endometrioid and clear cell carcinomas may suggest its role in the development of these tumor types.     

VEGF、p21ras在鼻咽癌组织中的表达及其临床意义的研究

目的 :研究 VEGF及 p2 1ras蛋白表达与鼻咽癌临床生物学特性及预后的关系 ,更好地评估预后 ,指导临床治疗。方法 :用免疫组化法测定 81例鼻咽低分化鳞癌 VEGF及 p2 1ras蛋白表达 ,对阳性和阴性病例进行统计分析。结果 :VEGF在不同分期、颈淋巴结转移、放疗后远处转移病例中的表达有显著性差异 (P<0 .0 5 ) ,p2 1ras蛋白高表达 ,但与不同分期、局部复发、颈淋巴结转移、远处转移无关。单因素分析显示影响鼻咽癌生存的预后因素有临床分期 (P<0 .0 5 )和癌组织中 VEGF表达水平 (P<0 .0 5 )。 Cox逐步回归模型分析显示临床分期是鼻咽癌的独立预后因素。结论 :鼻咽癌组织中 VEGF表达与临床 N分期、颈淋巴结转移、远处转移有显著相关 ;单因素分析 VEGF表达与鼻咽癌的预后呈正相关 ,可考虑作为预测鼻咽癌患者放射治疗后远处转移和预后的因素之一。 p2 1ras蛋白高表达 ,但与颈淋巴结转移、远处转移、局部复发无关 ,可作为联合检测的指标之一用于肿瘤的早期诊断。 VEGF表达与 p2 1ras蛋白表达无相关性。     

胸水中CEA CYFRA21-1 NSE和LDH对肺癌的临床诊断

目的:探讨CEA、CYFRA21-1、NSE、LDH水平对癌性胸水的诊断价值。方法:采用电化学发光方法检测胸水中的CEA、CYFRA21-1和NSE,采用酶法检测LDH。结果:恶性胸水的CEA、CYFRA21-1、NSE、LDH水平明显高于良性胸水(P<0.01),肺腺癌CEA明显高于鳞癌和小细胞肺癌(P<0.01),肺鳞癌CYFRA21-1水平明显高于腺癌(P<0.05)和小细胞肺癌(P<0.01),小细胞肺癌NSE明显高于鳞癌(P<0.01)。4项标志物联合检测的敏感性、准确性均比单项检测高。结论:联合检测胸水中的CEA、CYFRA21-1、NSE和LDH对肺癌的诊断具有重要的临床意义。     

Haptoglobin-related protein as a serum marker in malignant lymphoma

A novel serum 21 kDa haptoglobin-related protein (Hpr) was investigated in patients with malignant lymphoma, to evaluate its correlation with clinical and histologic features at presentation and its possible role as a tumor marker for patient outcome. One hundred fifty eight serum samples were taken from 88 patients with non-Hodgkin’s lymphoma (n=58) and Hodgkin’s disease (n=30) at presentation and in the course of follow-up. Sera from 61 healthy volunteers served as normal controls. Serum Hpr levels in the lymphoma patients (median 430xl0³ u/ml, range 0-4000xl0³) were significantly higher than in the control group (median 68xl0³ u/ml, range 0-180xl0³) (p=0.0001). Higher median Hpr values were detected in patients with advanced disease (p=0.013), “B” symptoms (p=0.029) and in males (p=0.053). There was also a significant correlation between Hpr and erythrocyte sedimentation rate (p=0.028). Serial determinations showed a significant decrease of the initial Hpr values obtained after treatment in 41 patients, 38 of whom achieved complete remission. In the follow-up period additional Hpr measurements were taken from 17 patients. Three of them eventually relapsed, and showed increased Hpr levels at the time of relapse. Hpr levels remained low in 11 of 14 patients who maintained complete remission, and increased in three. In conclusion, serum Hpr is a new serum tumor marker of potential use in the clinical setting of lymphoma. This work is dedicated to the memory of Dr. Arie H. Bartal, a dedicated oncologist and friend. This work was supported by Chemotech Thechnologies Ltd., by grant no. 3676 from the Chief Scientist’s Office of the Ministry of Health, Israel, and by the Fund for Promotion of Research in the Technion.     

CYFRA21—1,CEA联合测定对癌性胸水的诊断价值

检测１１８例胸水ＣＹＦＲＡ２１－１和ＣＥＡ浓度以及ＡＤＡ活性。其中癌性不６７例，结核性胸水４０例，其它良性渗漏液１１例。ＣＹＦＲＡ２１－１对癌胸水的敏感度为６２．６％，特异度为９０．２％，ＣＥＡ的敏感度为５５．２％，特异度为１００％。联合测定ＣＹＦＲＡ２１－１和ＣＥＡ对癌性胸水的敏感度可提高到８５．１％，其临床应用值值得重视。     

Analysis of the p21 gene in gliomas

The p21 gene encodes a cyclin dependent kinase inhibitor protein (p21) which has a tumor suppressive activity in a variety of tumor cell lines. Since, the p21 gene is up-regulated by the p53 tumor suppressor gene, which is frequently mutated in gliomas, acting therefore in the same control pathway, it constitutes a good candidate gene to be also inactivated in these tumors. To test this hypothesis, DNAs from 81 gliomas (48 glioblastomas, 11 anaplastic astrocytomas, 10 low-grade astrocytomas, 12 oligodendrogliomas and mixed gliomas), were investigated for mutations in the p21 coding sequence by denaturant gradient gel electrophoresis followed by sequencing. All these tumors have been previously screened for p53 mutations. Three different DNA variants were identified on codon 31 (17 cases), 27 (1 case) and 117 (1 case) and shown to be also present in matching constitutional DNA, suggesting they were polymorphisms. None of the tumors demonstrated a somatic mutation. No significant correlation between the presence of a p21 variant and the p53 mutation tumor status was observed. In conclusion, mutation in the p21 gene unlikely contributes to the development of gliomas.     

Detection of p21WAF1/Cip1 in brain metastases

The p21^WAF1/Cip1 (p21) protein, a negative regulator of G₁ checkpoint control, was overexpressed in the majority of human gliomas. To investigate whether p21 expression in brain metastases from various systemic origins is similar to that in gliomas and whether p21 expression is regulated differently in brain metastases and in corresponding primary tumors, we used immunohistochemical staining to examine the expression of p21 in paraffin-embedded sections prepared from primary colon and breast carcinomas and from metastatic brain tumors that originated from colon, breast, lung, and kidney cancers and from melanoma. Our results showed that 56% (28 of 50) of the brain metastases samples have more than 1% p21-positive staining cells compared with 87% of primary gliomas reported previously. Among the samples analyzed, p21 expression in brain metastases from breast carcinomas was much higher than in primary breast carcinomas. In contrast, p21 expression in brain metastases from colon carcinomas was less than primary colon carcinomas. The results from this pilot study suggest that p21 expression is regulated differently in metastatic and primary tumors.