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研究生(外文):I-Pei Chu
論文名稱(外文):Clinical Trial of Intratumoral Injecting Anti-tumorigenic Factors to Skin Tumors of Canines
外文關鍵詞:metforminaspirinserotoninintratumoral injection
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Cancer is the top one cause of death in dogs in recent year. Numerous researches against tumors make innovations for the past few years.
Retrospective studies showed metformin decreasing cancer risk in human diabetes patients. It was reported inhibiting cell proliferation and the hypothesis mechanisms were proposed that inhibit mTOR and activate AMPK pathways.
In this study, the multi-antitumorigenic agents, including metformin, aspirin and serotonin were injected directly into solid cutaneous masses. Treatment efficacy was measured by calculating the pre-injection and post-injection tumor volume change.
Twenty-nine canine patients were enrolled in the study, including sarcoma (12), carcinoma (14) and other types (3). The most tumor types were PNST (8) and hepatoid gland tumor (7). The tumor volume reduction was shown in18 patients and overall efficacy was 37.51%, including 7 complete remission, 11 partial remission, 7 stable disease and 4 progression disease. The influence factors of efficacy were including tumor type, tumor stage, and ratio of tumor volume and injection volume. Prolonging progression free interval (PFI) and disease free interval (DFI) were also noted at the end of this study. The toxicities were evaluated according to VCOG criteria and most of toxicities documented as grade I to II. Erythema, necrosis and discharge, pain sensation of the injection sites are most common side effects. Acceptable and tolerable toxic reactions were noted in most patients.
The results suggested this product can be used to inhibit tumor growth, reduce tumor volume and prolong PFI and DFI.

中文摘要 i
Abstract ii
Chapter I Introduction 1
Chapter II Literature review 5
2.1 Intratumoral injection 6
2.2 B10 formulation 7
2.2.1 Metformin 7
2.2.2 Aspirin 8
2.2.3 Serotonin 9
2.3 Background of metformin 9
2.4 Antitumor mechanisms of metformin 11
2.4.1 Direct and indirect effect 12
2.5 Background of aspirin 13
2.6 Antitumor mechanisms of aspirin 15
2.7 Background of serotonin 16
2.8 Antitumor mechanisms of serotonin 16
Chapter III Aim 18
Chapter IV Material and method 20
4.1 Patient selection 21
4.2 Patient evaluation 22
4.3 Treatment protocol 22
4.4 Response assessment 23
4.5 Assessment of toxicity 25
4.6 Statistical analysis 26
Chapter V Result 27
5.1 Animal patient demographic information 28
5.1.1 Patient Characteristics 28
5.1.2 Tumor types 28
5.1.3 Clinical staging 29
5.1.4 Formula group 29
5.2 Overall response 30
5.3 Response and influenced factors evaluation 31
5.3.1 Response of tumor types 31
5.3.2 Clinical staging 32
5.3.3 Rapid-onset and slow-releasing formula 33
5.3.4 PNST 33
5.3.5 Hepatoid gland adenocarcinoma and adenoma 34
5.4 Tumor volume and injection volume 34
5.5 PFI and DFI 36
5.6 Toxicity 38
Chapter VI Discussion 40
6.1 Overall response 41
6.2 Influenced factors evaluation 42
6.2.1 Tumor volume and injection volume 42
6.2.2 Tumor type 43
6.2.3 Tumor stage 45
6.2.4 Injection methods 45
6.3 PFI and DFI 46
6.4 Serotonin 47
6.5 Toxicity 48
6.6 Limitations in this study 50
Chapter VII Conclusion 51
Reference 53
Appendix 57

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