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Mtor In Squamous Cell Carcinoma Of The Oesophagus: A Potential Target For Molecular Therapy?

机译:食道鳞状细胞癌中的Mtor:分子治疗的潜在目标?

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Aims: The mammalian target of rapamycin (mTOR), an important regulator of protein translation and cell proliferation, is activated in various malignancies. In a randomised controlled trial of advanced renal cell carcinoma patients, targeted therapy to mTOR by means of rapamycin analogues has been shown to significantly improve survival. An in vitro study has revealed that mTOR is activated in oesophageal squamous cell carcinoma (OSCC) cell lines and that mTOR expression is inhibited by rapamycin. The objectives of this histological study were to determine the proportion of OSCC tissues with activated mTOR (p-mTOR) expression, thereby assessing the percentage of patients with OSCC that would possibly benefit from neoadjuvant rapamycin therapy, and to identify the clinicopathological features of these potentially rapamycin-sensitive tumours. Methods: The expression of p-mTOR (Ser2448) was immunohistochemicaliy assessed in a validated tissue microarray comprising triplicate tissue biopsy cores of 108 formalin-fixed, paraffin-embedded OSCCs. Staining results were correlated with clinicopathological data. Results: Normal oesophageal epithelium was negative for p-mTOR. Activated mTOR expression was located in the cytoplasm of oesophageal tumour cells. 26 (25%) of 105 assessable OSCCs showed tumour cells with positive staining for activated mTOR. Activated mTOR expression was associated with a lesser degree of differentiation only (p = 0.024). No correlation was detected between p-mTOR and the proliferation marker Ki-67. Conclusions: Activated mTOR can be detected in one-quarter of OSCCs. Since this subset of patients may potentially benefit from mTOR inhibiting therapy, a phase II clinical trial of neoadjuvant mTOR-inhibiting therapy in patients with OSCC may be considered.
机译:目的:雷帕霉素(mTOR)的哺乳动物靶标是蛋白质翻译和细胞增殖的重要调节剂,在多种恶性肿瘤中均被激活。在晚期肾细胞癌患者的随机对照试验中,通过雷帕霉素类似物对mTOR进行靶向治疗已显示可显着提高生存率。一项体外研究表明,mTOR在食道鳞状细胞癌(OSCC)细胞系中被激活,雷帕霉素抑制了mTOR的表达。这项组织学研究的目的是确定具有激活的mTOR(p-mTOR)表达的OSCC组织的比例,从而评估可能受益于新辅助雷帕霉素治疗的OSCC患者的百分比,并确定这些潜在的临床病理特征雷帕霉素敏感性肿瘤。方法:在经过验证的组织微阵列中对p-mTOR(Ser2448)的表达进行了免疫组织化学评估,该组织微阵列包含108个福尔马林固定,石蜡包埋的OSCC的三次组织活检核心。染色结果与临床病理数据相关。结果:正常食管上皮对p-mTOR阴性。活化的mTOR表达位于食道肿瘤细胞的细胞质中。在105个可评估的OSCC中,有26个(25%)的肿瘤细胞对激活的mTOR有阳性染色。激活的mTOR表达仅与较小的分化程度相关(p = 0.024)。在p-mTOR和增殖标记Ki-67之间未发现相关性。结论:在四分之一的OSCC中可以检测到激活的mTOR。由于这部分患者可能会受益于mTOR抑制疗法,因此可以考虑在OSCC患者中进行新辅助mTOR抑制疗法的II期临床试验。

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