细胞角蛋白19在口腔鳞状细胞癌中的表达及意义

目的:研究细胞角蛋白19 (cytokeratin 19,CK19)在口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)中的表达,探讨两者之间的相关性.方法:收集正常口腔黏膜、单纯上皮增生、上皮异常增生和OSCC患者活检标本49例,采用免疫组织化学、蛋白质印迹比较各组织中CK19的表达;收集未接受过放疗和化疗的OSCC患者16例及健康人群17例的血清,采用ELISA方法检测血清中CK19的可溶性片段CYFRA21-1的水平.采用SPSS17.0软件包进行数据处理.结果:CK19表达于有上皮异常增生的复层鳞状上皮基底上层和OSCC尤其是低分化鳞癌的癌细胞中,随上皮异常增生程度加重,CK19表达的阳性率、表达强度显著增加.OSCC患者血清CYFKA21-1含量显著高于健康对照组(P＜0.01).结论:CK19表达增加是口腔黏膜癌变过程中的早期事件,其异常表达可作为早期诊断OSCC的辅助指标之一.     

Monitoring gastric lymphoma in peripheral blood by quantitative IgH allele-specific oligonucleotide real-time PCR and API2-MALT1 PCR

Gastric extranodal marginal zone lymphoma (EMZL) often shows prolonged localised disease, but the present study demonstrated the presence of tumour cells in peripheral blood (PB) of low stage patients. We studied the presence of tumour cells in PB in gastric lymphoma patients harbouring or lacking t(11;18)(q21;q21), by real-time immunoglobulin (Ig)H allele-specific oligonucleotide-polymerase chain reaction (ASO-PCR) and API2-MALT1 PCR. Tumour cells were exclusively detected in PB of t(11;18)(q21;q21)+-EMZL patients. The presence of tumour cells in PB and gastric biopsy follow-up samples showed a good correlation in these patients, suggesting clinical relevance for monitoring of tumour cells in PB of gastric t(11;18)(q21;q21)+-EMZL patients.     

Expression of Bcl-2 family modulated through p53-dependent pathway in human hepatocellular carcinoma

The biological behavior of hepatocellular carcinoma (HCC) is, in part, relevant to apoptosis. A systematic investigation of the apoptosis-related Bcl-2 family modulated by p53 in HCC is lacking. A total of 22 HCC patients were studied. The expression of p53 protein in HCC was assessed using the immunohistochemical method, which categorized the HCC patients into two groups: group 1, with immunonegative p53 (N = 7); and group 2, with immunopositive p53 (N = 15). The expression of p53, p21, Bcl-2, Bax, Bcl-x_L, and Bcl-x_S in the 22 HCC cases detected by western bioting was quantified with a densitometer. The apoptosis of the 22 HCC cases was determined by terminal deoxynucleotidyltransferase-mediated UTP end-labeling (TUNEL). We found that Bcl-2 was remarkably up-regulated in group 2 (14 of 15), but was down-regulated in group 1 (5 of 7). Bax was up-regulated in both group 1 (6 of 7) and group 2 (13 of 15). Bcl-x_L was up-regulated in both group 1 (5 of 7) and group 2 (9 of 15). Bcl-x_S was remarkably down-regulated in group 2 (14 of 15) compared to group 1 (4 of 7). The apoptosis indexes of groups 1 and 2 were 0.82±0.26% and 0.33±0.17%, respectively (P = 0.023). The long-term survival of group 1 was superior to that of group 2 (log-rank test, P = 0.001). In conclusion, Bcl-2 and Bcl-x_S represented the most significant anti- and proapoptotic proteins, respectively, modulated through a p53-dependent pathway in HCC.     

Aberrant co-expression of CD19 and CD56 as surrogate markers of acute myeloid leukemias with t(8;21) in Taiwan

Aberrant antigen expression in acute myeloid leukemia (AML) has been extensively studied in the West with limited reports from Taiwan. We carried out this retrospective study to characterize the frequency and significance of aberrant antigen expression of AML in Taiwan. Among 111 cases, 58 (52%) showed aberrant antigen expression, most frequently CD7 (27%) and CD56 (23%). Aberrant CD7 expression was observed in all non-AML-M3 subtypes, most frequently in AML-M7 (4/6, 67%); while CD19 expression was only observed in AML-M2 (5/36, 14%). CD56 expression was most common in AML-M5 (4/8, 50%). The relative frequency of CD19 and CD56 expression in AML with t(8;21) was higher than those with other chromosomal abnormalities or normal karyotype (P = 0.011 and 0.005, respectively). In non-M3 AML, aberrant antigen expression was identified in 56/96 (58%) cases, in contrast to 2/15 (13%) AML-M3 cases (P = 0.001). CD7, CD19 and CD56 expression was not correlated with remission rate. We concluded that aberrant immunophenotype was more frequent in non-M3 leukemias in Taiwan. The relative frequency of CD19 and/or CD56 expression in AML with t(8;21) was significantly higher than those without this translocation and co-expression of these two antigens may serve as the surrogate markers for AML with t(8;21).     

Role of p21<Superscript>WAF1/CIP1</Superscript> as an attenuator of both proliferative and drug-induced apoptotic signals in <Emphasis Type="Italic">BCR-ABL</Emphasis>-transformed hematopoietic cells

The constitutive tyrosine kinase activity of the BCR-ABL fusion protein plays a crucial role in the pathogenesis of chronic myeloid leukemia and promotes growth factor-independent survival of hematopoietic cells. In 32D cells, expression levels of retrovirally transduced BCR-ABL were positively correlated with the levels of the cell cycle regulator protein p21, and this upregulation of p21 expression depended on the kinase activity of BCR-ABL. To assess the role of p21 on BCR-ABL-positive hematopoietic cells, we compared proliferation and drug-induced apoptosis in bone marrow (BM) cells from wild-type and p21 knockout mice after retroviral transfer of the BCR-ABL fusion gene. As compared with wild-type cells, p21 knockout cells showed increased proliferation, suggesting that p21 acted as an attenuator of BCR-ABL-mediated cell proliferation. In marked contrast, deletion of p21 promoted apoptosis induction by imatinib and taxol in BCR-ABL-transformed BM cells. These findings demonstrate that p21 has a dual function in BCR-ABL-transformed murine BM cells: It attenuates the effects of two apparently opposed phenomena such as BCR-ABL-mediated cell proliferation and drug-induced apoptosis. This dual function of p21 calls for a cautious evaluation of the suitability of p21 as a secondary target in anticancer therapy.     

宫颈鳞状细胞癌化疗前后小分子RNA-96的表达变化及其与化疗敏感性的关系

目的 探讨新辅助化疗对宫颈鳞状细胞癌小分子RNA-96(miR-96)表达的影响及其与化疗疗效、敏感性及临床病理特征之间的关系。方法 采用茎环实时荧光逆转录聚合酶链反应(RT-PCR)检测28例(Ⅰb2期～Ⅱa期)宫颈鳞状细胞癌患者新辅助化疗前、后癌组织中miR-96的表达,分析miR-96表达变化与新辅助化疗的疗效、敏感性及其与临床病理特征的关系。结果 RT-PCR 检测miR-96表达的敏感性和特异性良好;新辅助化疗前宫颈癌组织中miR-96的相对表达量是化疗后宫颈癌组织中的(5.330±5.069)倍,差异具有统计学有意义(P=0.000)。化疗前后miR-96的表达变化:中、低分化者(2.345±1.153)低于高分化者(9.941±5.359)(P=0.000);间质浸润深度＜1/2间质者(8.236±5.399)高于≥1/2间质者(1.978±1.030)(P=0.000);有淋巴结转移者(1.848±0.959)明显低于无淋巴结转移者(7.942±5.348)(P=0.000);而年龄≤45岁、＞45岁,临床分期为Ⅰb2期、Ⅱa期者化疗前后miR-96的表达变化差异无统计学意义(P＞0.05)。结论 新辅助化疗能有效降低宫颈鳞状细胞癌组织中miR-96的表达水平,因此测定化疗前宫颈癌组织中miR-96的表达水平对新辅助化疗疗效及敏感性预测具有一定参考价值。     

微小RNA-155反义寡核苷酸对乳腺癌MDA—MB-157细胞及裸鼠移植瘤的作用

目的：探讨微小RNA-155（microRNA．155,miR-155）反义寡核苷酸（antisenseoligonucleotide,AS0）对乳腺癌MDA-MB-157细胞增殖、凋亡及裸鼠移植瘤的作用。方法：设计合成化学修饰的miR-155ASO,通过Lipofectamine^TM 2000转染MDA-MB-157细胞,激光共聚焦检测转染率,real-timePCR测定转柒后miR-155表达水平的变化,CCK-8法检测细胞增殖抑制率,流式细胞仪检测细胞凋亡率,观察miR-155ASO对裸鼠成瘤能力的影响,免疫组织化学法检测瘤体组织Caspase-3的表达。结果：激光共聚焦检测转染率达80％以上。转染miR-155AS0后,miR-155表达明显下降,细胞增殖能力降低,凋亡增加。miR-155AS0能明显抑制裸鼠移植瘤生长,抑制率为52．98％,并且能显著增加Caspase-3的表达。结论：miR-155AS0能显著下调miR-155的表达水平,继而抑制乳腺癌MDA-MB-157细胞的增殖,促进其凋亡;并且通过增加靶基因Caspase-3的表达,抑制裸鼠移植瘤的生长,为miR-155作为乳腺癌治疗靶点提供了实验依据。