Investigating of the anti-oral cancer effects and mechanism of drugs in cell co-culture and in patient-derived tumor xenografts (PDTXs)
| Autor: | Yang, Cheng-Yu, 楊承育 |
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| Rok vydání: | 2016 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 105 Oral cancer is one of the most common cancers in the world, especially in Southeast Asia and Taiwan. Although the diagnosis and treatment of oral cancer in the past few decades has been progress, but the patient's survival and quality of life has not been considerable improvement. Local or regional recurrence and cervical lymph node metastasis remained as difficult clinical treatment challenges in oral cancer. It is urgent need to develop new diagnosis and treatment on oral cancer. Tumor survival environment is closely related with tumor occurrence, invasion, metastasis and absorption of drugs. Therefore, in addition to the traditional treatment, tumor microenvironment is a new target of tumor therapy. In the first part of this study, we investigated whether the triptolide (TPL) of Chinese herbal can inhibit the hallmarks of tumor in the simulated oral tumor microenvironment by co-culture system to achieve the anti-head and neck squamous cell Cancer (HNSCC). We demonstrated that TPL can inhibit the migration, invasion, angiogenesis factors, cytokines IL-6, IL-8 and TNF-α of oral cancer cells co-cultured with macrophage-like U937 cells by using co-culture system. Our results indicated that TPL is a potential candidate among novel chemotherapeutic agents or adjuvants for modulating tumor-associated macrophages in a tumor microenvironment of HNSCC. The second part of this study is investigated the molecular mechanism of melatonin in oral cancer by patient-derived tumor xenografts (PDTX). Melatonin is a versatile natural compound widely found in animals, plants and microorganisms, and has anti-cancer effects on various cancers, but its effect on oral cancer is unclear. In vivo animal models play an important role in the development of new drugs for cancer and their biological mechanisms. The PDTX models preserved the heterogeneity of the patient's primary tumor, including the tissue structure and matrix components of the original tumor, which are well representative of complex interactions between tumor cells and their microenvironments. Therefore, PDTX models can simulated response of drugs in patients more truly and can effectively evaluate the efficacy and safety of anticancer drugs in preclinical experiments, which can contribute to the development of clinical drugs. We have established oral cancer PDTX models and performed preclinical studies of melatonin. We also show that melatonin has antioral cancer ability. We used tissue microarray IHC staining to find that LSD1 / KDM1A can be as a novel biomarker in the diagnosis and treatment of oral cancer, and melatonin can inhibit the growth of oral cancer cells by inhibiting LSD1 / KDM1A. Our results indicated that melatonin has the potential as a novel chemotherapeutic agent or adjuvant against oral cancer. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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