Signal transduction activated by the cancer chemopreventive isothiocyanates: cleavage of BID protein, tyrosine phosphorylation and activation of JNK

Phenethyl isothiocyanate and allyl isothiocyanate induce apoptosis of human leukaemia HL60 cells in vitro. Apoptosis was associated with cleavage of p22 BID protein to p15, p13 and p11 fragments and activation of JNK and tyrosine phosphorylation (18 kDa and 45 kDa proteins). All these effects and apoptosis were prevented by exogenous glutathione (15 mM). Protein tyrosine phosphatase activity was unchanged. The general caspase inhibitor Z-VAD-fmk prevented apoptosis but not JNK activation - excluding a role for caspases in JNK activation, whereas curcumin prevented JNK activation but only delayed apoptosis. This suggests that in isothiocyanate-induced apoptosis, the caspase pathway has an essential role, the JNK pathway a supporting role, and inhibition of protein tyrosine phosphatases is not involved.     

THE EFFECT OF LOCAL RADIOTHERAPY ON T LYMPHOCYTE SUBSETS OF CANCER PATIENT

ＴＨＥＥＦＦＥＣＴＯＦＬＯＣＡＬＲＡＤＩＯＴＨＥＲＡＰＹＯＮＴＬＹＭＰＨＯＣＹＴＥＳＵＢＳＥＴＳＯＦＣＡＮＣＥＲＰＡＴＩＥＮＴ￥ＭａＨｕｉｍｉｎ；马惠民；ＺｈａｎｇＳｈａｎｗｅｎ；张珊文（ＤｅｐａｒｔｍｅｎｔｏｆＲａｄｉｏｔｈｅｒａｐｙ，Ｂｅｉｊｉｎ...     

蛋白酪氨酸磷酸化水平与乳腺癌细胞株抗失巢凋亡特性的关系

背景与目的：正常上皮或内皮细胞脱离与细胞外基质的联系时会发生失巢凋亡(anoikis),而大多数来源于上皮或内皮的肿瘤细胞则丧失了这种特性,多数相关研究表明肿瘤细胞的抗失巢凋失特性与细胞信号转导的异常密切相关。本研究初步探讨信号分子的蛋白酪氨酸磷酸化水平与肿瘤细胞抗失巢凋亡特性之间的关系。方法：用琼脂糖凝胶电泳检测DNA梯状带,用流式细胞术以及软琼脂集落形成实验等方法观察正常狗肾脏上皮细胞株MDCK(Madin-Darby canine kidney)和3种乳腺癌细胞株MCF-7、Bcap-37以及MDA-MB-231的抗失巢凋亡特性。同时分析广谱蛋白酪氨酸激酶抑制剂染料木黄酮(genistein)对肿瘤细胞这种特性的抑制作用,并通过western blot检测3种乳腺癌细胞在悬浮培养与贴壁培养时总体蛋白酪氨酸磷酸化水平的差异。结果：3种乳腺癌细胞均表现出明显的抗失巢凋亡特性,进一步的研究证明这种特性可被染料木黄酮所抑制。Western blot的结果显示与贴壁培养时相比,在悬浮培养的MDcK细胞中所有的蛋白酪氨酸的磷酸化水平均呈现下降趋势;而在肿瘤细胞中,尽管大多数蛋白质酪氨酸的磷酸化水平下降,但是可见有酪氨酸磷酸化水平异常增高的蛋白条带(幅度3．5～6．5倍)。结论：3种乳腺癌细胞均具有不同程度的抗失巢凋亡特性,而信号蛋白酪氨酸的异常磷酸化与这些肿瘤细胞的抗失巢凋亡特性有关。     

Serine 220 phosphorylation of the Merkel cell polyomavirus large T antigen crucially supports growth of Merkel cell carcinoma cells

Merkel cell polyomavirus (MCPyV) is regarded as a major causal factor for Merkel cell carcinoma (MCC). Indeed, tumor cell growth of MCPyV‐positive MCC cells is dependent on the expression of a truncated viral Large T antigen (LT) with an intact retinoblastoma protein (RB)‐binding site. Here we determined the phosphorylation pattern of a truncated MCPyV‐LT characteristically for MCC by mass spectrometry revealing MCPyV‐LT as multi‐phospho‐protein phosphorylated at several serine and threonine residues. Remarkably, disruption of most of these phosphorylation sites did not affect its ability to rescue knockdown of endogenous T antigens in MCC cells indicating that phosphorylation of the respective amino acids is not essential for the growth promoting function of MCPyV‐LT. However, alteration of serine 220 to alanine completely abolished the ability of MCPyV‐LT to support proliferation of MCC cells. Conversely, mimicking the phosphorylated state by mutation of serine 220 to glutamic acid resulted in a fully functional LT. Moreover, MCPyV‐LT^S220A demonstrated reduced binding to RB in co‐immunoprecipitation experiments as well as weaker induction of RB target genes in MCC cells. In conclusion, we provide evidence that phosphorylation of serine 220 is required for efficient RB inactivation in MCC and may therefore be a potential target for future therapeutic approaches.     

Src tyrosine kinase augments taxotere-induced apoptosis through enhanced expression and phosphorylation of Bcl-2

Activation of Src, which has an intrinsic protein tyrosine kinase activity, has been demonstrated in many human tumours, such as colorectal and breast cancers, and is closely associated with the pathogenesis and metastatic potential of these cancers. In this study, we have examined the effect of activated Src on the sensitivity to taxotere, an anticancer drug targeting microtubules, using v-src-transfected HAG-1 human gall bladder epithelial cells. As compared with parental HAG-1 cell line, v-src-transfected HAG/src3-1 cells became 5.9 and 7.0-fold sensitive to taxotere for 2 and 24-h exposure, respectively. By contrast, HAG-1 cells transfected with activated Ras, which acts downstream of Src, acquired approximately 2.5- approximately 4.8-fold taxotere resistance. The taxotere sensitivity in HAG/src3-1 cells was reversed, if not completely, by herbimycin A, a specific inhibitor of Src family protein tyrosine kinase, indicating that Src protein tyrosine kinase augments sensitivity to taxotere. Treatment of HAG/src3-1 cells with taxotere resulted in phosphorylation of Bcl-2 and subsequent induction of apoptotic cell death, whereas neither Bcl-2 phosphorylation nor apoptosis occurred in parental or c-H-ras-transfected HAG-1 cells. Interestingly, the Bcl-2 protein is overexpressed in v-src-transfected cell line, compared to those in parental or Ras-transfected cell line. Treatment of HAG/src3-1 cells with herbimycin A significantly reduced the expression and phosphorylation of Bcl-2, and abrogated taxotere-induced apoptosis, suggesting a potential role for Src protein tyrosine kinase in the taxotere-induced apoptotic events. H-7, a protein kinase C inhibitor and wortmannin, a phosphatidylinositol-3 kinase (PI-3 kinase) inhibitor, neither altered taxotere sensitivity nor inhibited taxotere-induced apoptosis in these cells. These data indicate that the ability of activated Src to increase taxotere sensitivity would be mediated by apoptotic events occurring through Src to downstream signal transduction pathways toward Bcl-2 phosphorylation, but not by activated Ras, PI-3 kinase or protein kinase C.     

Involvement of tyrosine phosphorylation of p185c-erbB2/neu in tumorigenicity induced by x-rays and the neu oncogene in human breast epithelial cells

Ionizing radiation is the exogenous agent best proven to induce breast cancer. c-erbB2/neu amplification and overexpression are known to occur in breast cancer and are correlated with aggressive tumor growth and poor prognosis. We have developed simian virus 40–immortalized cell lines from normal human breast epithelial cells (HBECs) with luminal and stem-cell characteristics. In this study, we examined whether x-rays and a mutated neu oncogene are capable of inducing tumorigenicity in these cells. The results indicated that x-rays were effective in converting immortal non-tumorigenic HBECs to weakly tumorigenic cells that then could be transformed to highly tumorigenic cells by the neu oncogene. The in vitro growth of these tumorigenic cells was significantly faster than that of the parental non-tumorigenic cells in growth factor– and hormone-supplemented or -depleted media. The neu oncogene, however, had no tumorigenic effect on immortal non-tumorigenic cells. The expression of p185^c-erbB2/neu was elevated in neu-transduced immortal or weakly tumorigenic cell lines. However, only in the latter was p185^c-erbB2/neu found to be phosphorylated at tyrosine residues. Thus, x-rays appear to induce a genetic alteration that confers weak tumorigenicity on immortal HBECs and interacts with p185^c-erbB2/neu directly or indirectly to give rise to fast-growing tumors. Mol. Carcinog. 21:225–233, 1998. © 1998 Wiley-Liss, Inc.     

中药联合放疗对中晚期食管癌患者T细胞亚群和IL-2表达的影响

目的：探讨中药联合放疗对中晚期食管癌患者T细胞亚群和IL-2表达的影响。方法：将40例患者随机分为对照组（单纯放疗）20例、治疗组（中药复方守宫散联合放疗）20例。分别采用单克隆抗体碱性磷酸酶法、ELISA放射免疫分析法对两组患者的T细胞亚群和IL-2进行检测。结果：治疗组在治疗后CD4＋、CD4＋/CD8＋均较治疗前有显著提高（P〈0.05）,治疗后CD8＋水平较治疗前有明显下降（P〈0.05）。对照组在治疗后CD4＋、CD4＋/CD8＋均较治疗前有明显下降（P〈0.05）,而CD8＋在治疗后较治疗前有显著提高（P〈0.05）。治疗组治疗后改细胞亚群改善情况明显优于对照组（P〈0.05）;治疗组治疗后IL-2表达较治疗前有显著提高（P〈0.05）,对照组治疗后IL-2表达较治疗前无明显差异（P〉0.05）,治疗组治疗后IL-2表达明显高于对照组（P〈0.05）。结论：复方守宫散不仅可调节、提高中晚期食管癌放疗患者的免疫功能,亦可减轻放疗对机体免疫功能的损害。     

Intracellular and extracellular domains of protein tyrosine phosphatase PTPRZ-B differentially regulate glioma cell growth and motility

Gliomas are primary brain tumors for which surgical resection and radiotherapy is difficult because of the diffuse infiltrative growth of the tumor into the brain parenchyma. For development of alternative, drug-based, therapies more insight in the molecular processes that steer this typical growth and morphodynamic behavior of glioma cells is needed. Protein tyrosine phosphatase PTPRZ-B is a transmembrane signaling molecule that is found to be strongly up-regulated in glioma specimens. We assessed the contribution of PTPRZ-B protein domains to tumor cell growth and migration, via lentiviral knock-down and over-expression using clinically relevant glioma xenografts and their derived cell models. PTPRZ-B knock-down resulted in reduced migration and proliferation of glioma cells in vitro and also inhibited tumor growth in vivo. Interestingly, expression of only the PTPRZ-B extracellular segment was sufficient to rescue the in vitro migratory phenotype that resulted from PTPRZ-B knock-down. In contrast, PTPRZ-B knock-down effects on proliferation could be reverted only after re-expression of PTPRZ-B variants that contained its C-terminal PDZ binding domain. Thus, distinct domains of PTPRZ-B are differentially required for migration and proliferation of glioma cells, respectively. PTPRZ-B signaling pathways therefore represent attractive therapeutic entry points to combat these tumors.     

蛋白酪氨酸磷酸酶基因、血管内皮生长因子在口腔鳞状细胞癌组织中的表达及意义

目的:探讨口腔鳞状细胞癌（OSCC）组织中的蛋白酪氨酸磷酸酶基因（PTEN）、血管内皮生长因子（VEGF）的表达及意义。方法:选取我院2015年4月至2017年9月获取的90例OSCC患者的肿瘤组织标本（OSCC组）和45例癌旁正常口腔黏膜组织标本（对照组）,采用免疫组织化学染色技术检测两组标本中PTEN蛋白、VEGF蛋白的表达情况,并分析不同病理学分级、临床分期、淋巴结转移的OSCC患者肿瘤组织中PTEN蛋白、VEGF蛋白阳性表达差异。结果:OSCC组标本中PTEN、VEGF蛋白阳性表达率分别为35.56%、75.56%,对照组标本中PTEN、VEGF蛋白阳性表达率分别为73.33%、31.11%,两组比较差异具有统计学意义（P＜0.05）;在Ⅲ期和Ⅳ期、低分化、发生淋巴结转移的OSCC患者组织中PTEN蛋白阳性表达率显著低于Ⅰ期和Ⅱ期、高分化和中分化、未发生淋巴结转移的OSCC患者,差异均具有统计学意义（P＜0.05）;在Ⅲ期和Ⅳ期、低分化、发生淋巴结转移的OSCC患者组织中VEGF蛋白阳性表达率显著高于Ⅰ期和Ⅱ期、高分化和中分化、未发生淋巴结转移的OSCC患者,差异均具有统计学意义（P＜0.05）。结论:OSCC组织中PTEN蛋白表达水平显著降低,VEGF蛋白表达水平显著升高,并且与肿瘤的发生发展关系密切。     

中药联合放疗对中晚期食管癌患者T细胞亚群和IL-2表达的影响

目的:探讨中药联合放疗对中晚期食管癌患者T细胞亚群和IL-2表达的影响。方法:将40例患者随机分为对照组(单纯放疗)20例、治疗组(中药复方守宫散联合放疗)20例。分别采用单克隆抗体碱性磷酸酶法、ELISA放射免疫分析法对两组患者的T细胞亚群和IL-2进行检测。结果:治疗组在治疗后CD4+、CD4+/CD8+均较治疗前有显著提高(P<0.05),治疗后CD8+水平较治疗前有明显下降(P<0.05)。对照组在治疗后CD4+、CD4+/CD8+均较治疗前有明显下降(P<0.05),而CD8+在治疗后较治疗前有显著提高(P<0.05)。治疗组治疗后改细胞亚群改善情况明显优于对照组(P<0.05);治疗组治疗后IL-2表达较治疗前有显著提高(P<0.05),对照组治疗后IL-2表达较治疗前无明显差异(P>0.05),治疗组治疗后IL-2表达明显高于对照组(P<0.05)。结论:复方守宫散不仅可调节、提高中晚期食管癌放疗患者的免疫功能,亦可减轻放疗对机体免疫功能的损害。     

Expression, Function and Activation of the Proto-oncogene c-kit Product in Human Leukemia Cells

The c-kil proto-oncogene encodes a receptor tyrosine kinase that is considered to play important roles in hematopoiesis. The proto-oncogene c-kit product is expressed on various types of human cell lines derived from leukemic cells of erythroid, megakaryocytic and mast-cell lineages. Also, the c-kit product is detectable in blast cells in most cases of acute myeloblastic leukemia (AML) and in some cases of chronic myelogenous leukemia (CML) in blastic crisis (BC). By contrast, little or no expression of c-kit is observed in human leukemia cell lines of lymphoid lineage and in blast cells in acute lymphoblastic leukemia (ALL). Tyrosine phosphorylation and activation of the c-kit product with the ligand for c-kit (stem cell factor: SCF) results in proliferation of some human leukemia cell lines, such as M07E, and blast cells in a substantial fraction of AML cases. In addition, SCF appears to have an activity in inducing differentiation of certain types of leukemic cells. In some cases, further, the c-kit product is found to be activated in leukemic cells even before the stimulation with SCF. These results suggest that c-kit may be involved in excessive proliferation and aberrant differentiation of human leukemia cells.     

肾癌术后免疫治疗T细胞亚群检测及疗效观察

目的:检测肾癌术后患者IL-2免疫治疗前后对外周血T淋巴细胞亚群的水平影响,进一步观察其对肾癌术后患者的疗效。方法:肾癌术后患者98例随机分为两组:实验组58例采用IL-2治疗,皮下注射小剂量（60-100万IU/次）,隔日1次,共3月,以后每年方案同前1年。对照组40例只给予肾癌根治术,不予免疫治疗。应用流式细胞技术检测两组患者不同时间段（治疗前,治疗后2月、6月）外周血CD3+、CD4+、CD8+、CD4+/CD8+,并进行对比研究。观察两组治疗后1年、3年生存率、生活质量(KPS)评分以及不良反应。结果:实验组与对照组CD3+、CD4+、CD4+/CD8+在治疗前无明显差异(P＞0.05),治疗后2月、6月较对照组明显升高(P＜0.05)。术后1年实验组生存率100％(58/58),对照组97.5%（39/40）,两者无明显差异(P＞0.05);术后3年实验组生存率84.5％（49/58）,明显高于对照组（67.5%,27/40)(P＜0.05)。实验组术后1年生活质量评分平均升高19.6分,3年生活质量评分平均升高11.5分,均明显高于对照组3.7分、1.4分(P＜0.05)。实验组不良反应共12例,均为一过性,未影响免疫治疗。对照组无相关不良反应。结论:肾癌根治术后应用IL-2进行免疫治疗,可以提高患者免疫水平,发挥抗肿瘤作用,提高生存率,改善生活质量,不良反应较轻。     

甘露聚糖肽口服液对癌症患者T淋巴细胞免疫调节效应的研究

目的研究甘露聚糖肽口服液对癌症患者外周血白细胞数目、T淋巴细胞总数、经植物血凝素(PHA)诱导的T淋巴细胞增殖的影响。方法以血常规、E玫瑰花环及MTT(methyl thiazolyl tetrazolium)比色法检测。结果白细胞数量有升高趋势,但统计学处理无显著性差异(P>0.05),甘露聚糖肽可以促进T淋巴细胞增殖及转化(P<0.05)。结论甘露聚糖肽口服液具有调节癌症患者外周血T淋巴细胞免疫功能的效应。     

Selection of highly responsive T cell receptors by an analysis combining the expression of multiple markers

The clinical success of T cell receptor (TCR) gene–transduced T (TCR-T) cell therapy is expected as one of the next-generation immunotherapies for cancer, in which the selection of TCRs with high functional avidity (high-functional TCRs) is important. One widely used approach to select high-functional TCRs is a comparison of the EC50 values of TCRs, which involves laborious experiments. Therefore, the establishment of a simpler method to select high-functional TCRs is desired. We herein attempted to establish a simple method to select high-functional TCRs based on the expression of T cell activation markers using the mouse T cell line BW5147.3 (BW). We examined relationships between the EC50 values of TCRs in interleukin-2 production and the expression levels of TCR activation markers on BW cells. In TCR-expressing BW cells stimulated with antigenic peptides, the CD69, CD137, and PD-1 expression was differentially induced by various doses of peptides. An analysis of TCRs derived from the tumor-infiltrating lymphocytes of murine melanoma and peripheral blood T cells of hepatocellular carcinoma patients treated with a peptide vaccination revealed that an analysis combining CD69, CD137, and PD-1 expression levels in BW cells stimulated with a single dose of an antigenic peptide selected high-functional TCRs with functional avidity assessed by EC50 values. Our method facilitates the section of high-functional TCRs among tumor-reacting TCRs, which will promote TCR-T cell therapy. The stimulation of BW cells expressing objective TCRs with a single dose of antigenic peptides and analysis combining the expression of CD69, CD137, and PD-1 allows us to select highly responsive TCRs.     

The effect of anticancer therapy on peripheral blood T and B lymphocyte counts and function.

Patients categorized according to tumor type were compared to a control non-tumor population. Comparison of relative T cell values among the groups showed no significant differences; however, when absolute numbers of T cells/mm3 were compared, all cancer patients, whether from treated or untreated groups, had significantly depressed T cell values. No significant differences were observed in the relative or absolute numbers of B cells. Comparison of the total lymphocyte response to PHA showed no significant differences among the various cancer groups; however, response in all cancer groups whether from treated or untreated patients, was depressed by comparison to the control group. Patients categorized according to the type of treatment received showed significant depression in the white blood count, lymphocyte count, relative and absolute T cell counts and the absolute B cell count in the postsurgery, postadjunctive therapy group. The pretherapy group also showed significant depression in the absolute number of T cells/mm3 when compared to the controls. Response to PHA correlated with the absolute T cells values.     

T细胞活化相关膜分子在非小细胞肺癌外周血中的表达及其临床意义

目的 :研究非小细胞肺癌患者外周血T淋巴细胞活化相关膜分子的表达 ,进一步探讨肺癌的免疫功能。方法 :应用流式细胞双色免疫荧光标记技术对 50例肺癌患者外周血T淋巴细胞活化相关膜分子CD3 PE和CD2 5 HLA DR CD69 FITC表达进行荧光免疫检测 ,并与正常对照组 (n =2 5)进行对比研究。结果 :50例肺癌患者外周血T淋巴细胞中CD3+ CD2 5+ 、CD3+ HLA DR+ 和CD3+ CD69+ 表达显著低于正常对照组 (P <0 .0 1 )。手术后外周血CD3+ CD2 5+ 、CD3+ HLA DR+ 和CD3+ CD69+ 表达高于手术前 (P <0 .0 1或P <0 .0 5) ,化疗前后差异无显著性 ;肺癌伴淋巴结转移CD3+ CD2 5+ 、CD3+ HLA DR+ 和CD3+ CD69+ 低于不伴淋巴结转移者 (P <0 .0 1 ) ;Ⅲ期、Ⅳ期和Ⅰ期、Ⅱ期之间CD2 5、HLA DR和CD69表达比较 ,差异有显著性 (P <0 .0 1 ) ;CD3+ CD2 5+ 、CD3+ HLA DR+ 和CD3+ CD69+ 表达与肺癌组织学分级及年龄有明显相关性 (P <0 .0 5或P <0 .0 1 ) ;与鳞癌和腺癌及患者的性别没有相关性。结论 :应用流式细胞仪检测外周血CD3+ CD2 5+ 、CD3+ HLA DR+ 和CD3+ CD69+ 的表达水平对了解患者的免疫状态、病情判断、预后评估及进行免疫治疗具有重要的意义     

巨噬细胞移动抑制因子对鼻咽癌细胞株MMP-2、MMP-9和IL-8表达的影响

背景与目的:鼻咽癌细胞较其它头颈部肿瘤具有更高的侵袭性和转移性,但其机制尚不清楚。本研究拟探讨巨噬细胞移动抑制因子(macrophagemigrationinhibitoryfactor,MIF)对癌细胞表达基质金属蛋白酶2、9(matrixmetalloproteinase2,9,MMP-2,MMP-9)和白介素8(interleukin8,IL-8)表达的影响。方法:采用流式细胞仪检测在MIF刺激前后鼻咽癌细胞CNE-1和CNE-2中MMP-2和MMP-9阳性癌细胞百分率的改变;蛋白印迹法和RT-PCR法分别用于检测肿瘤细胞中MMP-2、MMP-9的蛋白表达和mRNA表达的变化,而癌细胞分泌的IL-8水平则通过酶联免疫吸附法进行检测。结果:(1)经MIF诱导24h后,MMP-9阳性细胞比例在CNE-1和CNE-2细胞株中均明显增加,CNE-1细胞中由(28.5±2.5)%增加至(82.4±3.5)%(P=0.001),而CNE-2细胞中则由刺激前的(32.8±3.5)%增加至(86.1±1.6)%(P=0.002),但在两株癌细胞中,MMP-2阳性细胞比例在MIF刺激前后的变化并不明显(P>0.05);(2)MMP-9蛋白相对表达强度在两株细胞中也显著提高,CNE-1细胞从83.1±6.0增加至242.9±22.9(P=0.002),CNE-2细胞由84.4±4.3增加至278.9±29.7(P=0.003),但MMP-2蛋白表达强度在两株细胞中均无明显改变;(3)MIF刺激24h后,CNE-2细胞培养上清液中的IL-8浓度为(1201.8±593.3)pg/ml,显著高于未经刺激     

Oxidation and inactivation of low molecular weight protein tyrosine phosphatase by the anticancer drug Aplidin

The marine plitidepsin Aplidin derived from the Mediterranean tunicate Aplidium albicans is a strong apoptotic inducer with promising antitumor activity. However, little is known about the mechanism of action of the molecule. In this article, we report that Aplidin is cytotoxic for NIH3T3 cells and that its action is exerted through the production of reactive oxygen species (ROS). Rotenone, but not other selective inhibitors of ROS production, blocks the induction of ROS, suggesting the involvement of the mitochondrial respiratory chain in Aplidin action. The intracellular rise of redox potential caused by Aplidin inactivates several molecular targets. Among these targets, we focused our attention on protein tyrosine phosphatases (PTPs). In agreement with the well-characterized effect of ROS-mediated PTP oxidation, due to the presence of a cysteine residue in their catalytic site, we found that Aplidin induces a strong decrease in PTP activity. In particular, since the expression of low molecular weight-PTP (LMW-PTP) is strongly associated with tumor onset and progression, we investigated the effect of Aplidin on this enzyme. Our data show that LMW-PTP is oxidized and inactivated during Aplidin treatment, thus causing a hyper-phosphorylation of its substrate beta-catenin. These findings demonstrate that, at least in part, the antitumoral activity of Aplidin could be due to the direct inhibition of LMW-PTP and its related oncogenic potential.     

ＦＨＩＴ和ｍｄｍ２蛋白在非小细胞肺癌中的表达及意义

目的：探讨ＦＨＩＴ和ｍｄｍ２蛋白在非小细胞肺癌（ＮＳＣＬＣ）中的联合表达以及与临床病理特征之间的关系及意义。方法：采用免疫组化法（ＳＰ法）检测ＦＨＩＴ和ｍｄｍ２蛋白在５３例肺癌组织和１９例癌旁正常肺组织的表达情况,并结合肺癌的临床病理特征进行对比分析。结果：５３例肺癌组织ＦＨＩＴ蛋白失表达率６２.２６％,１９例癌旁正常肺组织１００.００％表达ＦＨＩＴ蛋白,二者差异显著（Ｐ＜０.０５）。有吸烟史的ＦＨＩＴ蛋白失表达率为７０.７３％,无吸烟史的为３３.３３％,二者差异显著（Ｐ＜０.０５）。ＦＨＩＴ蛋白失表达率与肺癌的病理类型、细胞分化程度、ｐＴＮＭ分期、淋巴结转移有密切关系（Ｐ均＜０.０５）,而与患者年龄及性别无关（Ｐ＞０.０５）。５３例肺癌组织ｍｄｍ２蛋白过表达率５２.８３％,１９例癌旁正常肺组织均不表达ｍｄｍ２蛋白,二者差异显著（Ｐ＜０.０５）。ｍｄｍ２蛋白过表达率与肿瘤分化程度、ｐＴＮＭ分期、淋巴结转移显著相关（Ｐ＜０.０５）,而与患者年龄、性别、吸烟史及不同的病理类型之间无关（Ｐ＞０.０５）。在ＮＳＣＬＣ中,ＦＨＩＴ与ｍｄｍ２蛋白的表达呈负相关（Ｐ＜０.０５）。结论：ＦＨＩＴ蛋白失表达和ｍｄｍ２蛋白过表达可能促进了肿瘤的恶性增殖及转移,联合检测上述二项指标,可以作为判断非小细胞肺癌的恶性程度、转移潜能以及预后的重要参考。