Two distinct genetic mutational pathways characterized by either chromosomal instability or high-frequency microsatellite instability (MSI-H) are recognized in the pathogenesis of colorectal cancer (CRC). Recently, it has been shown that patients with primary CRC that displays MSI-H have a significant, stage-independent, multivariate survival advantage. Biological properties of CMS1 (MSI-H type) can affect therapeutic efficiencies of agents used in the treatment of CRC, and therefore become a new predictive factor of the treatment. But, the predictive impact of MSI-H status for adjuvant chemotherapy remains controversial. This study will assess whether there is any unnecessary or inappropriate use of treatment agents recommended for adjuvant therapy of stage 2 and 3 of disease and for palliative or curative treatment of liver metastatic disease in microsatellite instability high group, a molecular subtype of colon cancer. Within this scope, the efficiencies of fluorouracil- and oxaliplatin-based chemotherapeutic agents will be shown on stage 3 microsatellite instability high colon tumor cell lines first, and then a microfluidic model will be created, imitating the metastasis of colon cancer to the liver. In the microfluidic chip model, we will create in liver tissue, where the metastasis of microsatellite instability high colon cancer will be simulated; the effectiveness of chemotherapeutic agents, immunotherapy agents, and targeted agents on tumor cells as well as drug response will be assessed according to cell viability through released biomarkers from the cells. The proposed hypothesis study includes the modeling and treatment of patient-derived post-metastatic liver cancer in microfluidics which has priority at the global and our region and consequently develop personal medication.

中文翻译：

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转移后肝生物芯片模型中微卫星不稳定性高结肠癌细胞的治疗药物效率的测定

在结直肠癌 (CRC) 的发病机制中，有两种以染色体不稳定性或高频微卫星不稳定性 (MSI-H) 为特征的不同基因突变途径。最近，显示 MSI-H 的原发性 CRC 患者具有显着的、独立于分期的、多变量生存优势。CMS1（MSI-H型）的生物学特性可以影响用于治疗CRC的药物的治疗效率，因此成为治疗的新预测因素。但是，MSI-H 状态对辅助化疗的预测影响仍然存在争议。本研究将评估是否有任何不必要或不当使用推荐用于疾病 2 期和 3 期辅助治疗以及微卫星不稳定性高组（结肠癌的分子亚型）肝转移性疾病的姑息性或治愈性治疗的治疗药物。在此范围内，基于氟尿嘧啶和奥沙利铂的化疗药物的疗效将首先在第 3 阶段微卫星不稳定性高的结肠肿瘤细胞系上显示，然后将创建微流体模型，模拟结肠癌向肝脏的转移。在微流控芯片模型中，我们将在肝组织中创建，模拟微卫星不稳定性高结肠癌的转移；化学治疗剂、免疫治疗剂的有效性，肿瘤细胞上的靶向药物以及药物反应将通过细胞释放的生物标志物根据细胞活力进行评估。拟议的假设研究包括在微流体中对患者衍生的转移后肝癌进行建模和治疗，这在全球和我们地区具有优先权，并因此开发个人药物。