骨肉瘤预后因素探讨

辅助化疗特别是新化疗的运用使骨肉瘤患者 5年生存率明显提高 ,但强化化疗也使患者发生化疗毒副作用的风险增大。病人所能承受的治疗风险是有限的 ,因此 ,必须对影响骨肉瘤预后的相关因素进行研究 ,以期实现治疗方法个体化以及利用能改善效果的所有治疗学科的办法 ,达到治愈和缓解的目的。许多学者对此进行了深入研究 ,本文将对影响骨肉瘤预后的各相关因素进行综述 ,从而为骨肉瘤的诊断及治疗方式的选择提供借鉴。1　影响骨肉瘤预后的临床因素1 .1　年龄患者的年龄是否具有预后意义一直存在争议。早在 1 975年 Ohno等[1] 对 1 30例骨肉瘤患…     

RNA干涉技术抑制骨肉瘤细胞MG63中Survivin基因表达的研究

目的：构建人Survivin基因的si RNA真核表达载体,探讨其对骨肉瘤细胞MG63中Survivin基因表达的干涉作用。方法：应用pSilencer3.0-H1neo构建Survivin特异性RNA干涉载体,转染MG63细胞,G418筛选稳定转染的细胞。HE染色观察细胞形态学变化,透射电镜观察细胞超微结构。应用RT-PCR、间接免疫荧光和western blot等方法检测Survivin的mRNA和蛋白水平变化。流式细胞仪检测细胞周期变化。结果：成功构建了Survivin基因si RNA真核表达载体PsvA和PsvB,获得了稳定转染的MG63细胞。与野生型MG63、阴性对照和MG63/PsvA细胞相比,MG63/PsvB细胞增殖反应明显减弱,差异有统计学意义,P〈0.01。MG63/PsvB细胞中Survivin mRNA和蛋白表达减少。与野生型MG63、阴性对照和MG63/PsvA细胞相比,MG63/PsvB凋亡率增加7倍（P〈0.01）。结论：特异性si RNA能够明显抑制Survivin基因在MG63细胞中的表达,为进一步研究survivn在MG63细胞中的生物学功能和作用机制奠定了基础。     

RNAi对骨肉瘤细胞株HMGA1基因表达及侵袭力抑制的实验研究

目的:探讨RNA干扰(RNAi)技术对骨肉瘤细胞株(MG-63)中HMGA1基因表达和侵袭力的影响.方法:采用单细胞克隆技术,从MG-63中分离培养出高表达HMGAl的骨肉瘤细胞株,将细胞分成3组,通过PU6mRFP载体进行转染:实验组,转染HMGA1的小干扰RNA(siRNA);阴性对照组,转染HMGA1的无关序列;细胞对照组为未转染的MG-63细胞.转染细胞株后,荧光检测转染效率;用实时荧光定量RT-PCR和蛋白质印迹法分别从mRNA和蛋白质水平检测siRNA对HM-GA1表达的影响;Transwell趋化侵袭实验观察转染后细胞株侵袭能力的变化.结果:荧光检测转染效率,实验组为(55.68±6.74)%,阴性对照组为(49.87±4.33)%;细胞对照组观察不到明显的荧光细胞.实验组HMGA1 siRNA转染骨肉瘤细胞后,明显下调细胞中HMGAl mRNA及蛋白的表达,与转染时间和转染浓度相关;阴性对照组和细胞对照组在转染前后HMGAl基因的mRNA及蛋白质表达均无明显变化.实验组细胞株穿过侵袭膜的细胞数明显低于阴性对照组和细胞对照组,P<0.01.结论:HMGAl siRNA可以下调骨肉瘤细胞中HMGAl mRNA及其蛋白的表达,抑制骨肉瘤细胞侵袭能力.     

HER2基因表达与骨肉瘤预后

目的:研究骨肉瘤中HER2基因的表达与临床预后的关系。方法:对82例骨肉瘤患者的临床病理资料进行回顾性研究,应用HER2单克隆抗体对组织切片进行免疫组织化学染色,并将上述资料与患者的预后进行分析。结果:骨肉瘤患者HER2表达与患者预后相关(P<0.05),HER2高表达的骨肉瘤患者预后较差。结论:HER2检测是骨肉瘤预后判断的一项有价值的指标;同时,HER2为骨肉瘤的治疗提供一种可能的生物靶点。     

p16蛋白在骨肉瘤的表达及与预后的关系

为研究Ｐ１６蛋白在骨肉瘤发生中的作用及对预后的影响，采用免疫组化方法观察４６例骨肉瘤标本中Ｐ１６的表达，结果表明，Ｐ１６蛋白表达阳性率为５２．２％，阳性率在各组织学类型及临床分期的病例中无显著性差异。在３１例有随访资料的骨肉瘤中，Ｐ１６阳性表达组１５例的术后生存期较Ｐ１６阴性组为长，且差异有显著性。，提示Ｐ１６基因变异可能在骨肉瘤发生中起一定作用，并影响预后。     

朊蛋白PrPc在Enneking III期骨肉瘤中的表达及预后相关性分析

目的：探讨朊蛋白PrPc（cellularprionprotein）在EnnekingIII期骨肉瘤中的表达以及分析其与骨肉瘤转移和患者预后的相关性。方法采用免疫组织化学法（SP法）对初诊已发生肺转移的EnnekingIII期骨肉瘤15例以及相应瘤旁组织中朊蛋白 PrPc 的表达进行检测。同时,检测同期收治的初诊未转移骨肉瘤标本33例作为对照组。比较已有转移的骨肉瘤和未转移骨肉瘤中 PrPc 蛋白的表达水平。对2006年1月至2009年12月收住院的两组骨肉瘤患者的临床资料进行回顾性分析。收集年龄、性别、肿瘤部位、肿瘤大小、病理性骨折、生存时间等资料。应用 Kaplan-Meier 法计算患者生存年率,应用 Log-rank 检验进行单因素分析,应用Cox回归模型进行多因素分析,探讨PrPc的表达和不同的临床特征与骨肉瘤患者预后生存率之间的关系。结果 PrPc蛋白在骨肉瘤组织中普遍表达,在瘤旁组织中不表达;EnnekingIII骨肉瘤中PrPc的表达要显著高于Enneking II期对照组（ P＝0.006）。Kaplan-Meier生存分析和Log-rank检验显示PrPc的表达水平与骨肉瘤患者预后相关（ P＝0.010）,Enneking分期与预后相关（ P＝0.025）。多因素分析显示,PrPc表达水平和肿瘤的Enneking分期可以作为骨肉瘤预后的独立影响因素。结论朊蛋白PrPc在已有转移的EnnekingIII骨肉瘤中的表达高于未转移患者。PrPc高表达的骨肉瘤患者预后较差。PrPc的高表达可能与骨肉瘤预后不良有一定相关性。     

骨肉瘤误诊误治30例的临床特征及预后分析

目的:比较误诊误治骨肉瘤患者与正确诊断和治疗骨肉瘤患者的临床特征和预后差异.方法:回顾性分析2007年1月-2010年2月共30例误诊误治骨肉瘤患者与60例正确诊断和治疗骨肉瘤患者的临床资料,并对预后进行随访,随访时间为6～60个月.比较2组患者年龄、性别、肿瘤部位、Enneking外科分期、Karnofsky体能状况(Karnofsky performance status,KPS)评分、病理类型、手术方式、肿瘤最大径、肿瘤坏死率、辅助化疗周期数、局部复发率和肺转移率的差异.应用Kaplan-Meier法计算2年生存率.结果:2组患者的性别、Enneking外科分期、KPS评分、肿瘤部位、病理类型、手术方式、辅助化疗周期数、局部复发时间和肺转移时间的差异无统计学意义(P＞0.05).误诊误治组发病年龄≥30岁的比例(分别为46.7％和11.7％,P＜0.001)、肿瘤最大径≥10 cm的比例(分别为50.0％和23.3％,P=0.011)、肿瘤坏死率＜90.0％的比例(分别为80.0％和60.0％,P=0.016)、局部复发率(分别为33.3％和10.0％,P=0.006)和肺转移率(分别为63.3％和43.3％,P=0.037)均较正确诊断和治疗组高.误诊误治组患者的中位生存时间为25.5个月(95％可信区间为7.1～58.9个月),正确诊断和治疗组患者的中位生存时间为38.0个月(95％可信区间为12.2～55.0个月),差异有统计学意义(P=0.025).正确诊断和治疗组患者的2年生存率(83.3％)明显高于误诊误治组(63.3％)(P=0.036).结论:年龄≥30岁的骨肉瘤患者易被误诊为良性疾病,对骨肉瘤的误诊误治可导致较高的局部复发率和肺转移率,并缩短生存期.     

骨膜骨肉瘤六例报告

骨膜骨肉瘤是Ｕｎｎｉ首先在１９７６年将之作为独立的肿瘤实体报告的,是骨表面骨肉瘤的一种。骨表面骨肉瘤还包括骨旁肉瘤,去分化骨旁肉瘤和高恶表面骨肉瘤。骨膜骨肉瘤的临床表现,影像学特征,病理学及预后均不同于其他３种骨表面骨肉瘤,现将骨膜骨肉瘤的有关问题进行探讨。材料与方法　１９９２年～１９９７年,收治６例骨膜骨肉瘤,男４例,女２例,年龄１２～３３岁,平均２１岁。位于胫骨上端干骺端偏干３例,股骨干中下段２例,股骨下端干骺端１例。Ｘ片示：肿块呈作者单位：１０００３５北京积水潭医院骨肿瘤科半球形附于骨皮质…     

鼻咽癌组织中Survivin的表达与预后关系

目的:检测IAP家族蛋白Survivin在鼻咽低分化鳞癌组织中的表达情况及其与鼻咽癌患者的临床特征及预后的关系。方法:免疫组化LSAB法检测92例初治无远处转移的鼻咽低分化鳞癌患者鼻咽肿瘤组织中Survivin的表达情况,分析其表达与各项临床指标的关系。KaplanMeier法分别分析Survivin的表达与鼻咽癌根治性放疗后总生存率的关系。用Cox风险比例模型进一步分析各预后指标与鼻咽癌患者总生存率的关系。结果:Survivin在鼻咽癌组织中表达的百分数平均为(37.24±30.94)%。以癌细胞表达( )以上(即>25%)为高表达的判断标准,则高表达率分别为56.52%(52/92)。在不同性别、年龄、鼻咽原发灶的侵犯范围、临床分期和有无局部复发、有无远处转移的病例中,鼻咽癌组织Survivin的表达情况差异无统计学意义,P>0.05;但是Survivin的高表达与有无颈部淋巴结转移有关,有颈部淋巴结转移的患者肿瘤组织Survivin高表达的比例增加,P<0.05。生存分析显示,Survivin低表达组和高表达组的患者5年累积总生存率分别为87.21%和52.28%(P=0.004);进一步的多因素Cox回归模型分析结果显示T分期和Survivin高表达与总生存率有关。结论:部分鼻咽癌组织中存在Survivin的高表达。其中Survivin的高表达与鼻咽癌患者颈部淋巴结转移及生存期的缩短有关。Survivin可作为鼻咽癌的预后指标。     

骨肉瘤的治疗与预后（附168例分析）

报告168例原发性骨肉瘤，男111例，女57例，年龄4－72岁，平均24岁，单纯化疗70例，手术加化疗87例，11例未作治疗，未作治疗者5年存活率为0，单纯化疗平均存活率15％，手术加化疗平均存活率20％，结果表明截肢术或局部肿瘤切除灭活植骨术加化疗使骨肉瘤病人5年存活率明显提高。     

CD9 expression is not a prognostic factor in human osteosarcoma

CD 9, also known as Motility-Related Protein-1 (MRP-1), is a member of the transmembrane four superfamily and plays a crucial role in cell adhesion, motility and signalling events. Downregulation of CD 9 has been reported to be associated with tumour progression, metastasis and clinical outcome in various kinds of solid tumours. Although prognosis of osteosarcoma has been improved by chemotherapy during the last decades, the problem of non-responders remains. At the present time prognostic factors at diagnosis have not been clearly identified. Furthermore, there is a need for markers that predict the response to chemotherapy at the time of biopsy, allowing stratification of osteosarcoma patients. In this study we investigated the effect of CD9 expression on the response to chemotherapy and survival in osteosarcoma. The expression of CD9 was examined immunohistochemically in 52 patients with high grade osteosarcoma and the results were correlated with histologic response to chemotherapy, 5 year disease free and 5 year overall survival. In patients with osteosarcoma 22 of 52 cases (42%) were positive for CD 9 expression, the rest were negative. CD 9 expression status showed no statistically significant correlation with response to chemotherapy; 41% had a poor response and 59% a good response in the CD9 positive group. In the CD9 negative group 57% had a good and 47% had a bad response. No significant difference was found when comparing disease free survival (58.9% in CD9 positive- versus 69.3% in CD9 negative tumours; P = 0.99) and overall survival of patients (54.0% in CD9 positive- versus 58.1% in CD9 negative tumours; P = 0.90) with CD9 expressing tumours to those with reduced CD9 expression. In conclusion our findings suggest that in contrast to solid tumours, CD9 is unlikely to provide any additional prognostic information for clinical purposes in osteosarcoma patients.     

NBS1 expression as a prognostic marker in uveal melanoma.

PURPOSE: Up to half of uveal melanoma patients die of metastatic disease. Treatment of the primary eye tumor does not improve survival in high-risk patients due to occult micrometastatic disease, which is present at the time of eye tumor diagnosis but is not detected and treated until months to years later. Here, we use microarray gene expression data to identify a new prognostic marker. EXPERIMENTAL DESIGN: Microarray gene expression profiles were analyzed in 25 primary uveal melanomas. Tumors were ranked by support vector machine (SVM) and by cytologic severity. Nbs1 protein expression was assessed by quantitative immunohistochemistry in 49 primary uveal melanomas. Survival was assessed using Kaplan-Meier life-table analysis. RESULTS: Expression of the Nijmegen breakage syndrome (NBS1) gene correlated strongly with SVM and cytologic tumor rankings (P < 0.0001). Further, immunohistochemistry expression of the Nbs1 protein correlated strongly with both SVM and cytologic rankings (P < 0.0001). The 6-year actuarial survival was 100% in patients with low immunohistochemistry expression of Nbs1 and 22% in those with high Nbs1 expression (P = 0.01). CONCLUSIONS: NBS1 is a strong predictor of uveal melanoma survival and potentially could be used as a clinical marker for guiding clinical management.     

ERCC1在结直肠癌组织中的表达及预后价值

目的:探究核苷酸切除修复交叉互补基因1（excision repair cross-complementation gene 1，ERCC1）表达对结直肠癌（colorectal cancer，CRC）患者铂类辅助化疗的预后价值。方法:选取2011年01月至2013年01月安徽医科大学附属六安医院行CRC根治术后接受mFOLFOX6方案化疗的患者共84例，通过免疫组化方法评估ERCC1在CRC组织中表达情况，分析ERCC1表达与预后的关联。结果:ERCC1高表达30例（35.7%）。Kaplan-Meier曲线显示ERCC1高表达的CRC患者无病生存期（DFS）和总生存期（OS）均缩短（P均<0.001）。多因素COX分析显示ERCC1高表达（DFS HR=4.645，95%CI:2.045~10.548，P<0.001；OS HR=4.898，95%CI:1.971~12.170，P<0.001）是CRC患者预后的不良因素，分析各亚组患者中ERCC1表达与生存相关性得到相似的结果。复发患者中ERCC1高表达的肝肺转移占68.8%（11/16），低表达的腹腔转移为70.0%（7/10），ERCC1表达与首次复发模式显著相关（P=0.006）。结论:ERCC1表达可作为评价CRC患者预后的重要指标。ERCC1表达可能有助于预测CRC患者辅助化疗后首次复发模式。ERCC1表达的预后价值需进一步研究。     

High expression of TIMP-1 in human breast cancer tissues is a predictive of resistance to paclitaxel-based chemotherapy

For breast cancer patients with lymph node metastasis, paclitaxel is the first-line chemotherapy drug. Clinical studies showed that some patients with breast cancer were insensitive to paclitaxel, which led to chemotherapy failure. Today, no validated markers exist for the prediction of chemotherapy sensitivity in this patient group. Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been shown to protect against apoptosis. Epidemiological studies have also associated elevated tumor tissue TIMP-1 levels with a poor response to cyclophosphamide/methotrexate/5-fluorouracil and anthracycline-based chemotherapy. Additionally, our previous study proved that TIMP-1 significantly decreased the sensitivity of breast cancer cells to paclitaxel-induced apoptosis by enhancing degradation of cyclin B1. These data imply that TIMP-1 may be a useful predictive biomarker for chemotherapy resistance. In this retrospective study, we investigated the association between expression levels of TIMP-1 protein in the primary tumor and objective response to paclitaxel-based chemotherapy in 99 patients with breast cancer. With Kaplan?CMeier survival analysis, the patients with high TIMP-1 levels were found to have significantly worse 5-year DFS (71.1?%) than the patients with low levels (88.5?%; P?=?0.020). Similarly, the patients with high TIMP-1 levels had significantly worse 5-year OS (78.9?%) than patients with low levels (96.7?%; P?=?0.004). In Cox??s univariate and multivariate analyses, TIMP-1 was prognostic for both DFS and OS. Our data showed that elevated tumor tissue TIMP-1 levels were significantly associated with a poor response to paclitaxel-based chemotherapy, and TIMP-1 might be a potential biomarker for predicting response of breast cancer patients to paclitaxel-based chemotherapy.     

High expression of MACC1 predicts poor prognosis in patients with osteosarcoma

Increasing evidence has demonstrated that high metastasis-associated in colon cancer-1 (MACC1) level is tightly associated with the development, progression, and poor prognosis of a variety of tumors. However, the relationship between MACC1 and the occurrence, development, and progression of osteosarcoma (OS) remains to be clarified. To facilitate and deepen the understanding of the associations of MACC1 with the development and progression of OS, in the current study, we detected the expressions of MACC1 mRNA and protein, and investigated the relationship between MACC1 expression and prognosis of the patients with OS. Our findings demonstrated that expressions of MACC1 mRNA and protein in OS tissues were significantly higher than those in paired normal bone tissues (P?<?0.05). Additionally, the level of MACC1 mRNA in the patients with higher clinical stage and distant metastasis was markedly higher than those with lower clinical stage and without metastasis (P?<?0.05). Furthermore, high MACC1 level was closely correlated with clinical stage and distant metastasis (P?<?0.05), but not related to the patients’ age, gender, tumor size, and anatomical location (P?>?0.05). Stepwise investigation revealed that survival time of the patients with high MACC1 level was obviously lower than that with low MACC1 level (P?<?0.05). Collectively, our data suggest that MACC1 may play important roles in the development and progression of OS, and thus may be considered as a novel molecular target for therapy of the patients with OS.     

Stim1在骨肉瘤组织和细胞中的表达水平及与顺铂耐药性的关系

目的:探讨Stim1在骨肉瘤组织和细胞中的表达水平及与顺铂耐药性的关系.方法:采用免疫组织化学染色检测了50例骨肉瘤患者的肿瘤组织中Stim1的表达.通过用高浓度的顺铂处理人骨肉瘤细胞系U-2 OS来建立耐药性骨肉瘤细胞(U-2 OS/DDP细胞).通过RT-PCR和蛋白质印迹检测细胞中Stim1、ATF4、CHOP和...     

HERG1 gene expression as a specific tumor marker in colorectal tissues

Introduction

Colorectal carcinomas exhibit a frequent recurrence after curative surgery, which may partially be due to histopathologically inconspicuous minimal residual disease. Reliable markers for tumor cells in colorectal tissue are still missing. Therefore, in this study we compared the predictive value of the putative tumor markers carcinoembryonic antigen (CEA), cytokeratin-19 (CK19) and cytokeratin-20 (CK20) to that of a novel marker, the human ether-a-go-go-related gene (HERG1) K⁺ channel, a suggested regulator of tumor cell proliferation.

Materials and methods

Using RT-PCR we studied HERG, CEA, CK19 and CK20 expression in colorectal carcinomas and non-carcinoma controls. HERG1 immunhistochemistry was performed in a total of 66 specimens, in colorectal carcinoma (n = 23), in matched histopathologically negative samples (n = 23) taken near the excision site from the same tumor patients and in healthy control biopsies (n = 20). In order to verify the relevance of HERG1 for tumor proliferation we studied the effect of HERG1 inhibition in the Colo-205 colon cancer carcinoma cell line using the MTT-assay.

Results

HERG1 was expressed in all tumor samples regardless of their stage and in adenomas larger than 0.4 cm, but absent in small adenomas, sigmadiverticulitis specimen and healthy histopathologically negative samples, except for one which developed a tumor recurrence. In contrast, CEA, CK19 and CK20 were absent in some tumors. The selective HERG1 inhibitor E-4031 dose-dependently impaired tumor growth in the proliferation assays.

Discussion

Our data indicate that HERG1, but not CEA, CK19 or CK20, is a highly sensitive and reliable tumor biomarker that may constitute a novel molecular target for tumor treatment.     

Rsf-1 overexpression serves as a prognostic marker in human hepatocellular carcinoma

Rsf-1 (HBXAP) was recently reported to be overexpressed in various cancers and associated with the malignant behavior of cancer cells. However, the expression of Rsf-1 and its clinical significance in human hepatocellular carcinoma (HCC) have not been reported. In the present study, we analyzed the expression pattern of Rsf-1 in human HCC tissues and found that Rsf-1 was overexpressed in 41.1 % of HCC specimens. There was a significant association between Rsf-1 overexpression and tumor stage (p?=?0.0322), AFP (p?=?0.0184), and tumor relapse (p?=?0.0112). Furthermore, Rsf-1 overexpression correlated with poor overall survival in HCC patients (p?p?=?0.0079). Small interfering RNA (siRNA) knockdown in SK-Hep-1 cells with high endogenous Rsf-1 expression inhibited cell proliferation and colony formation, with downregulation of cyclin E protein. In conclusion, Rsf-1 is overexpressed in HCCs and serves as a novel tumor marker. Rsf-1 contributes to hepatocellular carcinoma cell growth through regulation of cell cycle proteins.