 01 为什么要研究这个课题 也就是这个课题的重要性，比如该癌症在全世界排名，预后不好，治疗方法有限……，目的是说明我研究这个课题是非常有意义的，或者说是迫切需要的。 02 目前研究进展 要说明你是在充分研究了该课题方向的进展后，才决定做实验的，写清楚该领域的现状，目前已经取得的研究成果，这一部分需要大量的文献，不是文献堆积，而是用自己的语言总结出来。 03 提出问题 在目前研究成果的基础上，发现了尚未解决又亟需解决的问题，那么这个问题就是我这篇文章要解决的问题。 04 最后提出假说 我通过大量的文献及数据库分析，提出……的可能，也就是我这篇文章的主题 Gastric cancer (GC) constitutes a major cause of cancer-related deaths worldwide, but its management, especially in advanced stages, has evolved relatively little. Human epidermal growth factor receptor 2 (HER2/ErbB2/neu) is a 185-kDa transmembrane receptor tyrosine kinase (RTK) and a member of the epidermal growth factor receptor (EGFR) family [1].HER2 serves as an important therapeutic target for therapy in HER2-positive metastatic GC since its overexpression is found in more than 15% of GC and is associated with poor prognosis, particularly in the advanced stages of disease [2]. 有一部分胃癌患者HER-2阳性，存在这个治疗靶，这是我要研究的人群 For patients with HER2-positive advanced GC, trastuzumab (Herceptin, Genentech) combined with standard chemotherapy has been used as first-line treatment [2,3]. However, intrinsic and/or and acquired resistance totrastuzumab became a major obstacle in anti-HER2 therapy for advanced GC [2]. Thus, there is a need for alternatives to block HER2 signaling in GC.Lapatinib (Tykerb, GlaxoSmithKline, Ware, United Kingdom) is an oral dual tyrosine kinase inhibitor of EGFR (HER1) and HER2 [4]. Although lapatinib could be used for treatment of trastuzumab-resistant, HER2-positive advanced GC cases, the major problem of therapies targeting tyrosine kinases is that many tumors do not response or eventually developresistance to the drugs, often due to activation of alternative signaling pathways [5]. Therefore,it is important to know in advance which pathways could mediate resistance to the lapatinib treatment and to find ways of bypassing these obstacles [6]. 但是，经常因为靶向药物激活旁路而出现耐药，这是我今天要解决的问题 Mesenchymal-epithelial transition factor protein (MET), the hepatocyte growth factor(HGF) receptor, is a 190-kDa RTK, and plays a critical role in tumor growth, invasion and metastasis. MET is frequently overexpressed and activated in a subset of GC [7]. Previously it has been shown that co-expression of MET and HER2 in GC is associated with poorer survival compared to overexpression of either one [8]. Moreover, MET overexpression occurred more frequently in HER2-positive GCs than in HER2-negative GCs [9]. Growing evidences implicate the interplays between HER family receptors and MET in cancer cells through overlapping downstream signaling pathways [6]. In vitro cell culture experiments showed that HGF-induced MET activation was responsible for lapatinib resistance in HER2-positive GC cell lines [10, 11]. In addition, GC cells derived from HER2-positive and MET positive GC showed that the combination of lapatinib and MET-inhibitor offered a moreprofound cell growth inhibition than lapatinib alone [9]. Despite the strong evidenceregarding the interplay between MET and HER2 in GC, the current understanding of theregulation of MET expression and activation in relation to lapatinib-resistance in HER2-positive cells requires additional research.Forkhead box O1 (FOXO1) is a transcription factor and a member of the FOXO subfamily of the Forkhead/winged helix family [10]. Since FOXO1 activates or represses multiple target genes, and consequently regulates a variety of cellular functions [11], dysregulation of FOXO1 would subsequently result in various disease states such as cancer. FOXO1 inactivation has been documented in several cancers, including GC [12], and its association with several anti-cancer drugs has increasing attracted oncologists' attention [13-15]. The existence of a negative crosstalk between FOXO1 and HER2 in parental GC cell lines was previously reported [16]. This crosstalk was associated with cancer cell growth,epithelial-mesenchymal transition (EMT), cell migration and invasion in vitro as well as tumorigenicity and metastasis in vivo [16]. However, the relationship between FOXO1 andanti-HER2 drug resistance in GC has not been reported. 这句话承上启下，引出了我要研究的问题，也是该段落非常重要的一句话，指出了该研究的创新性何在 In the present study, lapatinib resistant GC cell lines (SNU-216 LR 2-8) were generated by chronic exposure to lapatiniband the potential role of FOXO1 in lapatinib resistance was examined. In addition, we silenced MET expression and investigated its implication in the lapatinib resistance in the lapatinib-resistant, HER2-positive GC cells.  引自文章：FOXO1 Suppression is a Determinant of Acquired Lapatinib-Resistance in HER2-Positive Gastric Cancer Cells Through MET Upregulation Introduction在描述前人完成的工作，应当使用一般现在时 【这篇文章的introduction写的逻辑性非常强，层层递进，最后点明主旨】 |
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