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轉譯癌症醫學實驗室簡介

Research Interest

Research Interest
    We, Laboratory of Translational Cancer Research are to investigate clinical associated cancer issues, especially on the topic of native Taiwan cancer – Head and neck cancer (HNC). HNC, including oral cavity cancer and pharyngolaryngeal cancer, is one of the ten frequent cancers in the world with an estimated over 500,000 new cases being diagnosed annually. In Taiwan, the incidence of HNC has become the top 5 th cancer in male after year of 2006, and is still increasing in recent years. Since this cancer usually occurs in the middle age male, at the high peak of life responsibility, it has tremendous impact of family and society.
   Head-neck cancer (HNC), including oral cancer and larynx cancer, is one of the ten frequent cancers in the world with an estimated over 500,000 new cases being diagnosed annually. In Taiwan, the incidence of HNC has become the 6th leading cancer, the 5th leading cancer in male in the year of 2007, and is still increasing in the recent years. Since this cancer usually occurs in the middle age male, at the high peak of life responsibility, it has tremendous impact of family and society.
    Epidemiologic studies have shown a wide variation range of incidence between worldwide areas. HNC is highly prevalent in Southeast Asia, comprising 30-35% of all malignancies in India, compared to approximately 10% in Taiwan and 2-4% in Western countries. Epidemiologic studies have shown a strong association between HNC and environmental carcinogens, especially the use of tobacco, alcohol, and areca nut. While tobacco smoking is a common habit in Western patients, areca nut chewing in India area, the both habits are frequently found In Taiwan patients. Therefore, the differential incidence of HNC may be attributed to certain environmental exposures, in addition to genetic factors.
    According to specific tumor subsite and individual clinical behavior, the treatment of HNC usually integrates with surgery, chemotherapy, and radiotherapy. In order to better serve patients and more comprehensively study this disease, we together with other multidisciplinary investigators and clinical physicians form the Chang Gung Head Neck Oncology Group. The goal of our laboratory is to systemic investigate the molecular carcinogenesis of HNC. The research topics include the carcinogenic mechanism of areca nut, searching of circulating tumor markers, identification of molecular pathogenic networks, and evaluations of prognostic factors. To reach these goals, we have established several HNC cell lines, as well as sublines with the characteristics of highly invasion, radioresistance, chmeoresistance, and chronic area nut exposure. We used advanced techniques, including microarray and bioinformatic analyses to global survey the genomic mutations, transcriptomes and proteomes of each specific cellular phenotype. We then used cellular and animal based methods to examine the molecular network pathways and biological functions of the genes that we defined. In addition, we performed clinical association study to evaluate the significance of the identified genes in clinicopathological presentations. Currently, several molecules that were first determined by us demonstrate contributing to HNC, such as DSG3, Grp78, Gp96, miR-10b, and miR-196. They functions on cellular growth, metastasis, chemo-radio-resistance and cancer stem cell conversion. We hope the results of our study can contribute to the knowledge in cancer field, as well further apply in clinical diagnosis, therapeutics, and prognosis to benefit medical society.

     

研究方向及研究室特色

我們轉譯癌症實驗室以研究臨床相關的癌症議題為主,並且致力於本土頭頸癌之研究。頭頸癌包含口腔癌、咽喉癌,是台灣十大癌症之一,且為十年來好發率攀升最快之癌症。因頭頸癌好發在中年男性,對家庭及社會無形中造成相當大的影響,因此,對頭頸癌致癌因子之研究,可說是刻不容緩。以流行病學的角度看,西方國家的頭頸癌占所有惡性腫瘤約3%,台灣占約10%,而好發最高的印度占約30%, 這些差異,除了族群基因體本身的因素外,可能也與所接觸的致癌因子有關,例如,印度地區常嚼食雪茄及成熟檳榔,台灣病患常是煙、酒、青檳榔合併習慣性使用,而西方國家並無嚼食檳榔的習慣。因為流行病學、致癌因子及臨床表徵上的差異極大,台灣頭頸癌之致癌機轉也可能其區域獨特性,必須國人自己投入來研究解決。

       頭頸癌依各部位與個別狀況,在臨床治療上,常結合手術與放射或化學治療,各專科醫師相互配合並分行其職,而我們實驗室也與臨床醫師們共同合作組成研究團隊,進行癌症轉譯相關議題的研究,內容含致癌因子機制、癌症分子病理,癌症標誌研發、分子標模式治療、預後評估分子標誌等,以期克服癌細胞特性,如快速生長、侵襲轉移、放化療抗性等問題。為達成這些目標,我們建立了數株本土頭頸癌細胞株,並具特殊細胞表徵之子株,如、高度侵襲性子株、抗放射子株、抗化藥子株、慢性檳榔暴露子株等,同時運用基因蛋白質體學等系統生物學方法,全面性探討與這些細胞表徵相關之基因轉譯圖誌,並以生物資訊和細胞動物模式,探討分子間的網絡途徑和基因功能,進行臨床相關性分析,以期系統性探討頭頸癌癌化之分子機制。目前我們已發現數個分子,首先報導與頭頸癌相關,如DSG3Grp78Gp96miR-10bmiR-196等,分別調控細胞侵犯轉移、調控癌幹細胞形成、或扮演抗放化療的角色等。未來,期望這些結果不只在癌症醫學知識有所貢獻,更能研發出有效輔助診治頭頸癌之工具,供臨床使用,使頭頸癌得以控制,增進台灣及國際社會的健康福祉。

 

 

 

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