- 學位論文
銜接臨床實務到基礎研究- 探討慢性鼻炎與腫瘤間之關係
From Bed to Bench - Investigate the Relationship Between Chronic Rhinitis and Tumors
摘要
炎症反應是人體防禦機制之一，短期急性炎症已被證明具有組織修復及重建之作用，然而，慢性炎症卻有可能引起糖尿病、心血管疾病、肺病或是癌症等。一直以來我們認為癌症的生成是因為細胞突變或致癌基因調控失衡所致。然而，近幾年越來越多的分子生物學研究結果顯示，炎症反應是癌化過程中之重要關鍵步驟。這種持續的發炎症狀被稱為準炎症（parainflammation），可能演變成長期慢性的發炎反應，或許可以解釋各種不同腫瘤新生的原因。在耳鼻喉頭頸外科的領域，慢性鼻炎是最為常見的一種疾病，根據臨床研究統計，在台灣的盛行率有30％以上，目前藥物治療主要為減少鼻部黏膜的發炎，並無徹底根治之道。另外，頭頸癌的病例有逐年升高的趨勢，其僅次於肺癌、肝癌和大腸直腸癌，在是男性中十大癌症排名第4，平均死亡年齡為54歲，較其他癌症早十年以上，影響社會及經濟甚鉅；目前的治療方式在第三、四期以合併外科手術切除、放射線治療與化學治療為主，五年存活率約只有40%。在此，我們有一個假說，頭頸黏膜細胞癌化的過程中，除了受到菸、酒、檳榔等因素的誘發外，也可能在慢性發炎（例如慢性鼻炎）環境下刺激而活化改變。本文透過臨床經驗的探討，再利用系統生物方法進行分析頭頸癌及慢性鼻炎之基因表現資料與生物標記，再以「同源藥理」、「藥理體」等嶄新舊藥新用策略，找出相關潛在藥物標靶。未來我們將深入探討慢性鼻炎影響頭頸腫瘤新生之關聯機制，相信本論文的結果，對頭頸癌與慢性鼻炎的治療具實質價值。
並列摘要
Inflammation is one of the body's defense mechanisms. Short-term acute inflammation has been shown to have tissue repair and reconstruction. However, chronic inflammation may cause diabetes, cardiovascular disease, lung disease, or cancers. We believe that cancer is caused by mutations in cells or imbalances in the regulation of oncogenes. However, in recent years, more researches in molecular biology have shown that inflammation is an important and critical step in the process of tumorigenesis. This persistent inflammation, called para-inflammation, may evolve into a chronic inflammatory response that maybe explain the causes of various new tumors. In the field of otolaryngology-head and neck surgery, chronic rhinitis is one of the most common diseases. According to clinical statistics, the prevalence rate in Taiwan is more than 30%. At present, drug treatment is mainly able to alleviate inflammation of the nasal mucosa, and there is no radical cure for the disease. In addition, the incidence of head and neck cancers (HNCs) have a tendency of increasing year by year. They are second only to lung cancer, liver cancer, and colorectal cancer. The prevalence of HNCs is lower than that of lung, liver, and colorectal cancers. It is the fourth most common cancer in men, and the average age of death due to HNCs is 54 years, which is at least 10 years earlier than that due to other cancers; early death has considerable social and economic effects. At present, the current treatment is mainly a combination of surgical resection, radiotherapy, and chemotherapy in the third and fourth phases, and the 5-year survival rate is only approximately 40%. Here, we have a hypothesis that in the process of tumorigenesis of head and neck mucosal cells, except caused by cigarettes, alcohol, and betel nut, it may also be activated and changed in the condition of chronic inflammation (such as chronic rhinitis). Through the exploration of clinical experience, this paper uses system biological methods to analyze genes and biomarkers of HNCs and chronic rhinitis, and we used homopharma and pharmacomics to identify new drug targets. In the future, we will explore the association between chronic rhinitis and HNCs. We believe the study will provide greater value for the clinical treatment, for the benefit of patients with HNCs and chronic rhinitis.
參考文獻
延伸閱讀
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