目的：藥用真菌牛樟芝具有多種生物學活性，特別是在各種體外和體內動物模型中均顯示出抗腫瘤作用。這項案例報告的目的是說明皿培牛樟芝對乳腺癌和小細胞肺癌患者的治療效果，並確定口服給藥的療效和持續時間。方法：所有受試者參加研究前均已徵得其知情同意。病例報告由佛教慈濟醫學基金會花蓮慈濟醫院研究倫理委員會批准（批准代碼：CR108-05和CR108-06）。選擇一名乳腺癌癌患者和一名小細胞肺患者。收集並分析了磁共振成像、電腦斷層掃描、血液生化檢查、alpha-N-乙醯乳糖胺酶(Nagalase)檢查和循環腫瘤細胞（CTC）檢查的所有數據。結果：皿培牛樟芝使兩名癌症患者的腫瘤縮小，每天給藥10克，超過6個月。通過多種信號通路介導的免疫調節和細胞抑製作用，皿培牛樟芝延長患者的生存期。包括癌症標誌物在內的實驗室測試結果表明，患者的身體狀況已有明顯改善，在某些情況下，恢復了正常水平。皿培牛樟芝可防止藥物引起的肝損傷並增強輔助治療的療效。結論：皿培牛樟芝可能具有抗癌作用，可導致癌症腫瘤縮小。顯然，它與營養保健品一樣可以延長無病進展期癌症患者的預期壽命。皿培牛樟芝可以用作補充藥物，從而提高患者的總體生存率和生活品質。

Objective: Medicinal fungus Antrodia cinnamomea (AC) possesses numerous biological activities especially anti-tumor effects shown in various in vitro and in vivo animal models. The aim of this case report is to demonstrate the therapeutic effect of dish-cultured AC (DAC) on breast cancer (BC) and small cell lung cancer (SCLC) patients and determine the efficacy for oral administration and length of duration. Methods: All subjects gave their informed consent for inclusion before they participated in the study. The case reports were approved by the Research Ethics Committee of Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation (Approval code: CR108-05 and CR108-06). One BC patient and one SCLC patient were selected. All data of MRI (Magnetic Resonance Imaging), CT (Computed Tomography), blood tests, Nagalase test and CTC (Circulating Tumor Cells) test were collected and analyzed. Results: DAC shrinks the tumor on the two cancer patients with 10 g daily administration for more than 6 months. It prolongs survival in patients achieved by DAC’s immunomodulatory and cytostatic effects mediated by multiple signaling pathways. Laboratory tests results including cancer markers indicated that patient’s physical conditions improved significantly and in some cases, regained the normal level. DAC protected against drug-induced liver injury and enhanced therapeutic effects of adjuvant therapy. Conclusion: DAC may exert an anti-cancer effect which leads to the regression of cancer. Apparently, it performs as do nutraceuticals to prolong life expectancy in cancer patients with progression-free. DAC may be used as a complementary medicine, thereby improving benefits of patient in overall survival and quality of life.

Motivation and aims....1
Chapter 1 Introduction....3
Chapter 2 Literature review....7
2.1 Small cell lung cancer (SCLC)...7
2.2 Breast cancer (BC).......7
2.2.1 BC and bone metastases...7
2.2.2 Preferred treatment option for hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2) -negative metastatic BC......8
2.2.3 Prognostic predictive biomarkers for BC......9
2.3 Periodontal disease: an incurable chronic inflammatory syndrome....12
2.3.1 Infectious burden.12
2.3.2 Periodontal Disease and Oxidative Stress.15
2.3.3 Inflammatory mechanisms of atherogenesis..15
2.3.4 The oral infectious theory of atherogenesis..18
2.3.5 Mechanisms of oral bacteria induced atherosclerosis.19
2.3.5.1 Endothelial cell invasion.19
2.3.5.2 Endothelial activation......21
2.3.5.3 Toll-like receptors mediated mechanisms....21
2.3.5.4 Autoimmunity..23
2.3.5.5 Metalloproteinase and oxidative stress mediated mechanisms...24
2.3.5.6 Assessment of exposure..24
2.3.6 The oral inflammatory theory of atherogenesis.25
2.3.6.1 Periodontal diseases and systemic biomarkers of inflammation.25
2.3.6.2 Sources of systemic inflammatory mediators in periodontal diseases ...26
2.4 Antrodia cinnamomea’s (AC) biological activity.......28
2.4.1 AC possess various bioactive compounds......28
2.4.1.1 AC’s anti-diabetic effect..29
2.4.1.2 AC’s hepatoprotective effect.......30
2.4.1.3 AC’s reno-protective effect......31
2.4.1.4 AC as a biotherapeutic approach to curing periodontitis31vi
2.4.2 Anticancer effects of AC.....33
2.4.2.1 Anti-lung cancer effects of AC........34
2.4.2.2 Anti-breast cancer effects of AC......35
2.5 Cultivation of AC..36
Chapter 3 Material and methods.....37
3.1 Case report........37
3.2 Methanol extract preparation procedures...........37
3.3 Quantification of the content of index compounds.....38
Chapter 4 Results...........39
4.1 Patient Case 1.......39
4.2 Patient Case 2...........40
4.3 HPLC profiles of methanol extract of DAC....44
Chapter 5 Discussion.....45
5.1 Patient Case 1...45
5.2 Patient Case 2...47
5.3 HPLC profiles of methanol extract of DAC....54
Chapter 6 Conclusion and perspective....55
Chapter 7 Future work.....57
Reference....59
Figures....83
Tables..........101

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