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肺类癌和神经内分泌癌之间血管生成的激活差异很大,并且对类癌肿瘤发生至关重要。

Activation of angiogenesis differs strongly between pulmonary carcinoids and neuroendocrine carinomas and is crucial for carcinoid tumourgenesis.

作者信息

Mairinger Fabian D, Walter Robert F H, Werner Robert, Christoph Daniel C, Ting Saskia, Vollbrecht Claudia, Zarogoulidis Konstantinos, Huang Haidong, Li Qiang, Schmid Kurt W, Wohlschlaeger Jeremias, Zarogoulidis Paul

机构信息

1. Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany;

1. Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; ; 2. Ruhrlandklinik, West German Lung Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany;

出版信息

J Cancer. 2014 May 15;5(6):465-71. doi: 10.7150/jca.9235. eCollection 2014.

Abstract

BACKGROUND

Lung cancer still remains the leading cause of cancer for men after prostate cancer and breast cancer for women. Angiogenesis is considered a major microenvironment modifier.

MATERIAL AND METHODS

Demographic data and study design; The study is based on a collective of twenty representative specimens of each tumour entity (Typical Carcinoid, Atypical Carcinoid, Large-Cell Neuroendocrine Carcinoma , Small Cell Lung Cancer) for mRNA expression analysis. The following methods were performed: RNA Extraction and RNA Integrity Assessment, NanoString CodeSet Design and Expression Quantification, NanoString Data Processing and Statistical Analysis.

RESULTS

KDR rendered significant association to aggressiveness of the tumour and decreases with increasing malignancy (p=0.049). A decreased expression of HIF1A and KDR mRNA as associated with a higher risk of tumour invasion in vessels (HIF1A: p=0.034; KDR: p=0.029). FIGF and HIF1A expression levels are significantly associated with progression-free survival (FIGF: p= 0.021; HIF1A: p= 0.049). CRHR2 and FLT4 are stronger expressed in female than in male patients (CRHR2: p=0.024, FLT4: p=0.004). FIGF expression is still significant between LCNEC and SCLC (p=0.023). FLT4 and KDR show highly significant association to one of the analysed groups (FLT4: p=0.001; KDR: p=0.006). Additionally, HIF1A expression differs significantly between these focus cohorts (p=0.018).

CONCLUSION

We should consider for clinical practice application which factors affect most the tumour growth and distal metastasis, thereafter investigate easy to administer drugs with low side effects. Probably a cluster system of therapy should be established where a drug targets simultaneously different pathways of the same origin.

摘要

背景

肺癌仍是男性继前列腺癌之后、女性继乳腺癌之后的主要癌症死因。血管生成被认为是主要的微环境调节因素。

材料与方法

人口统计学数据及研究设计;本研究基于每种肿瘤实体(典型类癌、非典型类癌、大细胞神经内分泌癌、小细胞肺癌)的20个代表性标本进行mRNA表达分析。采用了以下方法:RNA提取及RNA完整性评估、NanoString编码集设计及表达定量、NanoString数据处理及统计分析。

结果

KDR与肿瘤侵袭性显著相关,且随恶性程度增加而降低(p = 0.049)。HIF1A和KDR mRNA表达降低与肿瘤血管侵袭风险较高相关(HIF1A:p = 0.034;KDR:p = 0.029)。FIGF和HIF1A表达水平与无进展生存期显著相关(FIGF:p = 0.021;HIF1A:p = 0.049)。CRHR2和FLT4在女性患者中的表达强于男性患者(CRHR2:p = 0.024,FLT4:p = 0.004)。FIGF表达在大细胞神经内分泌癌和小细胞肺癌之间仍有显著差异(p = 0.023)。FLT4和KDR与其中一个分析组高度显著相关(FLT4:p = 0.001;KDR:p = 0.006)。此外,这些聚焦队列之间HIF1A表达差异显著(p = 0.018)。

结论

我们应在临床实践应用中考虑哪些因素对肿瘤生长和远处转移影响最大,进而研究易于给药且副作用小的药物。可能应建立一种联合治疗体系,使一种药物能同时靶向同一来源的不同途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4103/4066358/7dcd0c8b9d77/jcav05p0465g001.jpg

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