Magister Scientiae (Medical Bioscience) - MSc(MBS) / Laboratory studies, epidemiological investigations and human clinical trials indicate that flavonoids have important effects on cancer chemoprevention and therapy. Flavonoids may interfere in several steps that lead to cancer development but may also lead to toxicity as the inhibition of carcinogen-activating enzymes may also cause potential toxic flavonoid-drug interactions. However, the potential toxicity of these dietary components has not been well studied. The use of polyphenol enriched supplements prepared from South African herbal teas, rooibos(Aspalathus linearis)and honeybush (Cyclopia spp.) are being marketed to alleviate symptoms that are known to be “cured” by the herbal teas. However, there is a lack of information regarding the possible health promoting effects of these polyphenol-enriched extracts on xenobiotic metabolism. In the present study, the modulating effects of aspalathinenriched rooibos and mangiferin-enriched C. genistoides and C. subternata extracts on the gene expression of xenobiotic metabolising enzymes (XMEs) were investigated in vivo in the rat liver and kidneys. An in vitro study, utilising a primary rat hepatocyte cell model, was included to further evaluate changes in the expression of selected XMEs by the herbal tea extracts, including their major polyphenolic constituents, aspalathin and mangiferin. The use of the in vitro primary hepatocytes assay as a predictive cell model for the modulation of the expression of XMEs genes by the herbal tea extracts in vivo was critically evaluated.In the liver and kidneys, the C. subternata polyphenol-enriched herbal tea extract effected the majority of changes regarding the expression of XMEs genes when compared to the rooibos and C. genistoides. Variations in the modulation of gene expression of the XMEs by the herbal tea extracts were related to differences in their polyphenol constituents, although non-polyphenolic constituent could also be involved.Overall the herbal teas regulated alcohol,energy, drug and steroid metabolism in the liver, whereas in the kidneys the gene expression of phase I, phase II, steroid metabolising enzymes, as well as drug transporters were modulated. It would appear that the herbal teas are likely to exhibit both beneficial and adverse effects in vivo,depending on the specific organ, the xenobiotic and/or drug that are involved. The primary rat hepatocytes model display varying effects with respect to modulating gene expression of specific XMEs by the polyphenol-enriched herbal tea extracts. Apart from the reduction in 17 -hydroxysteroid dehydrogenase gene expression care should be taken to directly extrapolate the in vitro findings to changes that prevail in vivo.However, interesting results regarding the masking effect of complex mixture on the modulation of XME gene expression of individual polyphenols were encountered. In addition differences in the dose and duration of exposure between the in vitro and in vivo studies were not comparable and should be further explored to validate the in vitro primary hepatocytes model to predict changes in vivo. Future studies should investigate the effects of the herbal tea extracts, its polyphenols and metabolites on XME induction at a protein level as well as varying herb-drug-enzyme interactions.

繼人體基因圖譜於2000年解碼後，基因解讀及研究初期均在競爭解讀基因序列(Gene sequences)，然而了解基因序列是一件事，如何從序列中來了解基因功能所賦予之生理生化意義，比如每段基因所產生之蛋白質產物、及蛋白質與細胞之間的相互關係等資訊，進而應用於藥物標的之尋找，才是未來生物醫學發展之主要方向。同理，藉由基因功能學(Functional Genomics)領域來研究新發現之基因的功能、基因表現、與蛋白質產物，進而辨識有用的藥物標的(Drug target)及尋找新的疾病治療方法，才是基因解讀後最主要之生技醫療市場。全球生物科技之應用中以醫療用的生技產品所帶來的產值最為可觀，佔總體生技產業約七成以上之產值，其中又以重組蛋白藥品、單株抗體、疫苗及檢驗試劑之研發為主要重心，其中行政院更在“加強生物技術產業推動方案”裡，特別將蛋白藥物、抗癌藥物開發及檢驗試劑等領域列為重點推動項目，國內外許多生物科技公司研發專長及主軸亦座落於全球最熱門的生技製藥發展脈絡上。目前由於許多癌症、代謝失常疾病、遺傳性疾病及自體免疫疾病等，臨床之治療藥物仍舊是付之闕如或是供不應求，其中特別是各種癌症以及自體免疫疾病，如類風濕性關節炎、多發性硬化症、牛皮癬及過敏等，都是生技醫藥開發非常重要之疾病研究領域。現今臨床上所常用的藥物，普遍有特異性不佳、副作用大的缺點，因此國內外許多生物科技公司正戮力於針對上述疾病類別找尋合適之生技藥物或是小分子藥物，已達到標的治療(Target therapy)為目的；然而在生技醫藥公司草創初期，大都以技術掛帥，且由於藥品開發時間冗長，因此鮮少有生技醫藥公司能於設立初期10年內有產品上市，因此導致初期營運風險居高不下，令投資者裹足不前，所以如何評估具有成長潛力之生技醫藥公司頗為困難，因此本論文擬從生技藥品著手，除了傳統從技術面、產品面、市場面、競爭者、人力資源、策略經營等構面著手分析成長中之生技醫藥公司外，由於生技醫藥產業之特殊屬性，所以更特別注重產業成長時針對生物倫理面的考量，以做為生技醫藥公司具成長潛力之指標之一。希望透過多元的評估分析，能夠歸納出生技醫藥公司的成功要素，並藉此分析能夠有系統的篩選出具成長性、具社會責任之生技醫藥公司，才能擘畫生技醫藥公司維持長期競爭力、獲得永續發展的遠景，並藉此做為投資者長期投資評估之參考依據。 / The completion of the human genome project is regarded as a turning point in biotechnology and medicine. This project is expected to produce sequence of DNA representing the functional blueprint and evolutionary history of the human species. As we entered the postgenomic era, what we faced is the explosion of new information, which is leading to dramatic changes in the way we are able to study and manipulation of life. At the first few years, many groups were competing in sequence decoding. However, the findings of the functions of genes and the interactions of different gene products are the main issues helping us exploit the new biotechnology markets. Through the research of functional genomics to explore the function, expression, and protein products of novel genes is helpful in identifying new drug targets and developing therapeutic strategies in treating various diseases. This is what we emphasized in biotech market after entering the postgenomic era. The most valuable branch of biotechnology industry is the medical products in global biotechnology market. The medical products take up to 70% of total sales in biotechnology markets. Among the medical biotechnology field, recombinant protein drugs, monoclonal antibodies, vaccines, and detection kits have been focused in pharmaceutical R&D investment. Executive yuan of the Republic of China decided to emphasized in protein drugs, anti-cancer drug development and detection kits in their “ The promotion plan of improving biotechnology industry”. Currently, the drugs against cancers, metabolic diseases, inherited diseases, and autoimmune diseases are still unavailable. Especially the drugs for various cancers, and autoimmune diseases including rheumatoid arthritis, multiple sclerosis, psoriasis, and allergy are under intensive investment in global biotechnology industry. This is because the drugs used today have the deficiencies including low specificity and adverse side effects. Thus, target therapy using monoclonal antibodies and small molecular drugs are the goals for worldwide biotech companies. However, the development in research has been considered as the most important thing in the starting stage of newly founded biotech companies and the long time needed for putting a new drug to market make very few biotech companies have salable products. Thus, the newly biotechnology company has been considered has high risk in the beginning stage. This makes investors to hesitate in putting their money in this field. To evaluate the potential of a new biotechnology companies is difficult since the complex of this industry. This study will try evaluating a newly founded biotechnology company not only through technology, product, market, competitors, human resources, strategies, but also from the consideration in bioethics. Hopefully, through the evaluation of multiple markers, we can conclude the essential factors for a successful company and screen out the company with high growing potential via this study. Finally, this study might serve as a reference for investors in evaluating a promising company for long-term investment.