| 摘要: | 癌症是由於細胞的基因發生突變，突變的發生除了基因自然突變之外，生活環境(例如，暴露於有毒化學藥劑、紫外光、輻射線與病毒感染等)與老化，皆會增加基因發生突變的機會。2011年，癌症分子生物科學家Douglas Hanahan 與 Robert A. Weinberg在Cell期刊，發表一篇回顧文章，歸納10種與癌症相關的分子標誌，例如：細胞過度增生、細胞不死與誘導血管新生等癌症分子標誌。每一個分子標誌皆說明各機制中，發生變異的基因與基因間(或者基因與蛋白質間)的相互作用。該文章不僅整合癌症的特點及指標，也詳述了癌症細胞發展的組織原則，同時也指出未來癌症治療的方向。2013年，美國癌症基因體圖譜計畫TCGA（The Cancer Genome Atlas），在Nature期刊發表一系列文章，說明不同類型的癌症，例如，惡性子宮內膜癌、惡性乳癌與卵巢癌，分享相同的突變基因，例如，PTEN、CTNNB1、PIK3CA、ARID1A與KRAS等。西方醫學治療癌症之方法發展至今，除了基本腫瘤手術切除、放射性治療與化學性治療外，還有針對癌症類型的標靶治療。隨著癌症擁有不同的分子標誌，若能針對突變基因的多種路徑，做多重性標靶個人化治療，將會為未來癌症治療帶來曙光。
擁有兩千多年歷史的中國傳統醫學，已有個人化醫療的概念。西元1973年，在湖南省長沙馬王堆三號西漢古墓出土了馬王堆醫書，被人文歷史學家認為是最早的中醫醫書。在馬王堆醫書中記載，醫者是透過判斷脈象來診斷患者之疾病。醫者經由為患者診脈方式瞭解個人之臟腑經絡，判斷其體質之虛實、冷熱，根據疾病所致之症候輕重，分別給予具緩解功能之針灸、中草藥物(單/複方)，用以調節個人陰陽氣血之平衡。
本研究利用台灣健保局資料庫，分析了2007年共187,230個中醫癌症處方，其中涵蓋了30種類型的常見癌症。根據本論文發現，一個中醫癌症處方平均為兩味複方與四味單方所組成，其中複方在處方中扮演主要的角色，而單方則扮演輔助與微調的角色。在所有處方中，為健保給付所包含的中草藥之單/複方(共746種科學中藥)做重量與排名分佈，並發現重量與排名之分佈，遵循齊普夫分佈。 中草藥單/複方之重量百分比越重，則其排名之名次越高。因此，名次越高之單/複方，是處方中重要的成分。依據中草藥之單/複方重量做排名的中醫癌症處方，能夠明顯地被齊普夫分佈法，將中醫癌症處方分類為良性與惡性腫瘤之處方，其中惡性腫瘤處方的齊普夫指數比良性腫瘤處方低。齊普夫指數越低，代表處方中之單/複方(之重量百分比)越相近，同時也意味著齊普夫指數較低的惡性腫瘤之疾病複雜度高。除此之外，本論文亦將癌症處方按照中草藥之單/複方的功能與特性，分別為各類癌症做分類。中草藥單/複方依照，清代汪昂的著作《醫方集解》(西元1682年)，將單方依照四氣與五味分類；複方分為21類，分別為30種癌症做分類。階層式層級法分析結果，所有的中草藥單/複方能明顯地被階層式分析法，將中醫癌症處方分類為良性腫瘤與惡性腫之不同的群組，且惡性腫瘤的群組間距離相近之處方，推論是按其身體解剖部位與生理功能所開立。由於處方中多為有補養、和解與理血功能等為主的複方與寒苦性等之單方，因此本論文推斷，中醫視癌症為陰虛與血瘀之熱性症候的疾病。此外，本論文將處方依四季分類，透過主成分分析法分析數據，發現四季中之處方，屬秋季進入冬季的處方變化差異最大，而造成差異之氣象因素為溫度下降。
本論文也探討30種類型的癌症之處方與其中單/複方之功能與特性，並將常用之中草藥單/複方，對應於西醫已知的10種癌症分子標誌(hallmarks of cancer)。如西醫觀點認為癌細胞過度增生的分子標誌，中醫則利用癰瘍之劑功能的複方與寒性的單方來治療，化解體內氣血毒物、幫助手術傷口癒合與抑制發炎反應。本論文並對各別癌症處方做深入的研究，發現各類型的癌症依據其不同的解剖位置與生理功能會有常用的組合，包含複方-複方、複方-單方與單方-單方的中草藥組合。整理出中醫癌症處方，針對每一種癌症類型排名最常使用的前12名複方與單方草藥與其功能。例如：歸類為理血之劑之桂枝茯苓丸最常與，歸類為和解之劑的加味逍遙散作組合，適用於治療女性的子宮肌瘤。本論文透過健保資料，將中醫處方與西醫疾病做對接，未來期望利用生物實驗與臨床試驗證明中醫處方之效果。
According to World Health Organization report, cancer is the number one cause of mortality worldwide. Most cancers develop because of mutations in genes. Many environmental risk factors increase mutations, leading people to cancer. DNA mutations maybe passed from parent to child. For example, cancers of the breast, ovary and colon sometimes run in families. In addition, the most important risk factor for cancer is growing older. Moreover, tobacco use, UV light, ionizing radiation, certain viruses, or other factors in person’s lifestyle or environment can cause mutations in cells. Over time, cells become cancerous after mutations accumulate in the various genes that control cell proliferation.
In 2011, Douglas Hanahan and Robert A. Weinberg published a review article, identifying 10 hallmarkss features in the carcinogenic process. For example, evading growth suppressors, sustaining proliferative signaling and inducing angiogenesis are important hallmarks. Cells acquired hallmark capabilities for tumor growth and progression. These hallmarks have provided a useful conceptual framework for understanding the complex biology of cancer. For clinical trials, people can be treated with a combination of drugs to against each of the capabilities.
Traditional Chinese medicine (TCM) is a system of theories and therapies in ancient Chinese, dating back 2100 years. According to TCM theories, an imbalance in the individual’s body can cause disease. TCM practitioners usually make diagnosis, called Zheng, by observation, inquiry, smelling/listening, and palpation. After the individual’s Zheng is determined, a TCM prescription is made.
In our study, we analyzed 187,230 TCM prescriptions to 30 types of cancer in Taiwan in 2007. The big data was retrieved from the National Health Insurance reimbursement database (Taiwan). We found that one TCM cancer prescription consist of two formulas and four herbs on average. We found the percentage weights of TCM formulas and herbs in one prescription allow the Zipf’s law with an exponent 0.6. We also found prescriptions for benign tumors have a larger Zipf’s exponent than prescription for malignant cancers. Furthermore, we found the combinations of formulas and herbs are specific to sites of origins of cancers. From the TCM functions of dominant formulas and natural of dominant herbs, we found that cancers are a ‘warm and stagnant’ syndrome in TCM perspective. We show that cancer patients with a secondary morbidity, stomach disorder and sleep disturbance, were prescript by peptic and tranquilizing formulas, respectively. We also analyzed TCM prescriptions by seasons and identified that temperature drop correlates with changes in TCM prescriptions in Taiwan.
Furthermore, we analyzed prescriptions for individual cancers. Top 12 formulas and 12 herbs were identified. In addition, we identified the most common combinations between formulas and herbs, formulas and formulas, and herbs and herbs for each cancer. As an example, for uterine leiomyoma, the most common combination is Gui Zhi Fu Ling Wan (carbuncle treating) and Jia Wei Xiao Yao San (mediating). The findings of our study provide insight to TCM cancer treatment, helping a dialogue between modern western medicine and TCM for better cancer care. |
