跳到主要內容

臺灣博碩士論文加值系統

(3.236.124.56) 您好!臺灣時間:2021/08/02 06:53
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:朱怡蓓
研究生(外文):I-Pei Chu
論文名稱:評估犬隻皮膚腫瘤內注射抗腫瘤因子其抑制之效果
論文名稱(外文):Clinical Trial of Intratumoral Injecting Anti-tumorigenic Factors to Skin Tumors of Canines
指導教授:李繼忠李繼忠引用關係
口試委員:廖泰慶林辰栖李雅珍
口試日期:2015-06-24
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:臨床動物醫學研究所
學門:獸醫學門
學類:獸醫學類
論文種類:學術論文
論文出版年:2015
畢業學年度:103
語文別:中文
論文頁數:75
中文關鍵詞:每福敏阿斯匹靈血清素腫瘤內注射
外文關鍵詞:metforminaspirinserotoninintratumoral injection
相關次數:
  • 被引用被引用:0
  • 點閱點閱:255
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
腫瘤是近幾年犬隻死亡原因的第一位,然而並非所有類型腫瘤對於傳統治療方式皆有良好反應。多種新穎抗腫瘤方式近年也廣大進行試驗。
回溯性研究發現人類第二型糖尿病患者,相較於其他用藥,使用每福敏治療者,明顯降低腫瘤的發生率,因此每福敏被認為抑制細胞增生,而其作用機制推測為抑制mTOR及活化AMPK路徑。
在此研究中,我們以局部腫瘤內注射抗腫瘤因子,包含每福敏、阿斯匹靈及血清素,以提升局部藥物濃度增加抗腫瘤效果。治療療效以治療前後腫塊體積的變化去做比較。
完成試驗的29隻皮膚腫塊的犬隻,其中12隻為肉瘤類腫瘤,14隻為上皮來源腫瘤,另外3隻則無法歸類為上述兩類型。腫瘤類型以周邊神經髓鞘瘤以及圍肛瘤為最大宗。最終試驗結果顯示,18隻病患腫瘤有反應,整體腫塊的消退率平均達到37.15%,其中7隻病犬達到完全消退,11隻部分消退,7隻腫塊穩定,另外4隻最終腫塊變大。影響作用的因子包含腫瘤類型、腫瘤臨床分期以及腫塊體積與注射量的比例關係等。延長腫瘤進展時間與無病期也是藥物作用的效果。依據獸醫癌症協會,多數副作用為程度一至二,包含局部注射部位發炎紅腫、腫塊壞死分泌物與注射後疼痛反應。大部分病患的副作用為侷限性且可回復性。
研究顯示腫瘤內注射抗腫瘤因子,對於犬隻皮膚腫塊有一定的消退效果,並且能夠延長病況進展時間或是無病時間。

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


1.Alimova, I.N., Liu, B., Fan, Z., Edgerton, S.M., Dillon, T., Lind, S.E., Thor, A.D., 2009. Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitro. Cell cycle 8, 909-915.
2.Ben Sahra, I., Laurent, K., Loubat, A., Giorgetti-Peraldi, S., Colosetti, P., Auberger, P., Tanti, J.F., Le Marchand-Brustel, Y., Bost, F., 2008. The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level. Oncogene 27, 3576-3586.
3.Buzzai, M., Jones, R.G., Amaravadi, R.K., Lum, J.J., DeBerardinis, R.J., Zhao, F., Viollet, B., Thompson, C.B., 2007. Systemic treatment with the antidiabetic drug metformin selectively impairs p53-deficient tumor cell growth. Cancer Res 67, 6745-6752.
4.Currie, C.J., Poole, C.D., Gale, E.A., 2009. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia 52, 1766-1777.
5.Decensi, A., Puntoni, M., Goodwin, P., Cazzaniga, M., Gennari, A., Bonanni, B., Gandini, S., 2010. Metformin and cancer risk in diabetic patients: a systematic review and meta-analysis. Cancer Prev Res res 3, 1451-1461.
6.Dizeyi, N., Bjartell, A., Hedlund, P., Tasken, K.A., Gadaleanu, V., Abrahamsson, P.A., 2005. Expression of serotonin receptors 2B and 4 in human prostate cancer tissue and effects of their antagonists on prostate cancer cell lines. Eur Urol 47, 895-900.
7.Dovizio, M., Tacconelli, S., Sostres, C., Ricciotti, E., Patrignani, P., 2012. Mechanistic and Pharmacological Issues of Aspirin as an Anticancer Agent. Pharmaceuticals 5, 1346-1371.
8.Dowling, R.J.O., Goodwin, P.J., Stambolic, V., 2011. Understanding the benefit of metformin use in cancer treatment. Bmc Med 9.
9.Gay, L.J., Felding-Habermann, B., 2011. Contribution of platelets to tumour metastasis. Nature reviews. Cancer 11, 123-134.
10.Geissler, C., Hambek, M., Eckardt, A., Arnoldner, C., Diensthuber, M., Stover, T., Wagenblast, J., 2012. The role of recombinant epidermal growth factor and serotonin in the stimulation of tumor growth in a SCCHN xenograft model. Oncol Rep 28, 785-790.
11.Goldberg, E.P., Hadba, A.R., Almond, B.A., Marotta, J.S., 2002. Intratumoral cancer chemotherapy and immunotherapy: opportunities for nonsystemic preoperative drug delivery. J Pharm Pharmacol 54, 159-180.
12.Goodwin, P.J., Ennis, M., Pritchard, K.I., Trudeau, M.E., Koo, J., Madarnas, Y., Hartwick, W., Hoffman, B., Hood, N., 2002. Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. J Clin Oncol 20, 42-51.
13.Hardie, D., Alessi, D.R., 2013. LKB1 and AMPK and the cancer-metabolism link - ten years after. BMC Biology 11, 36.
14.Henriksen, R., Dizeyi, N., Abrahamsson, P.A., 2012. Expression of serotonin receptors 5-HT1A, 5-HT1B, 5-HT2B and 5-HT4 in ovary and in ovarian tumours. Anticancer Res 32, 1361-1366.
15.Jalving, M., Gietema, J.A., Lefrandt, J.D., de Jong, S., Reyners, A.K., Gans, R.O., de Vries, E.G., 2010. Metformin: taking away the candy for cancer? Eur J Cancer 46, 2369-2380.
16.Lammers, T., Peschke, P., Kuhnlein, R., Subr, V., Ulbrich, K., Huber, P., Hennink, W., Storm, G., 2006. Effect of intratumoral injection on the biodistribution and the therapeutic potential of HPMA copolymer-based drug delivery systems. Neoplasia 8, 788-795.
17.Landman, G.W., Kleefstra, N., van Hateren, K.J., Groenier, K.H., Gans, R.O., Bilo, H.J., 2010. Metformin associated with lower cancer mortality in type 2 diabetes: ZODIAC-16. Diabetes care 33, 322-326.
18.Launay, J.M., Birraux, G., Bondoux, D., Callebert, J., Choi, D.S., Loric, S., Maroteaux, L., 1996. Ras involvement in signal transduction by the serotonin 5-HT2B receptor. J Biol Chem 271, 3141-3147.
19.Li, D., Yeung, S.C., Hassan, M.M., Konopleva, M., Abbruzzese, J.L., 2009. Antidiabetic therapies affect risk of pancreatic cancer. Gastroenterology 137, 482-488.
20.Li, D.H., 2011. Metformin as an antitumor agent in cancer prevention and treatment. J Diabetes 3, 320-327.
21.Libby, G., Donnelly, L.A., Donnan, P.T., Alessi, D.R., Morris, A.D., Evans, J.M., 2009. New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes care 32, 1620-1625.
22.Martin-Castillo, B., Dorca, J., Vazquez-Martin, A., Oliveras-Ferraros, C., Lopez-Bonet, E., Garcia, M., Del Barco, S., Menendez, J.A., 2010. Incorporating the antidiabetic drug metformin in HER2-positive breast cancer treated with neo-adjuvant chemotherapy and trastuzumab: an ongoing clinical-translational research experience at the Catalan Institute of Oncology. Ann Oncol 21, 187-189.
23.Memmott, R.M., Mercado, J.R., Maier, C.R., Kawabata, S., Fox, S.D., Dennis, P.A., 2010. Metformin prevents tobacco carcinogen--induced lung tumorigenesis. Cancer Prev Res (Phila) 3, 1066-1076.
24.Ogino, S., Kirkner, G.J., Nosho, K., Irahara, N., Kure, S., Shima, K., Hazra, A., Chan, A.T., Dehari, R., Giovannucci, E.L., Fuchs, C.S., 2008. Cyclooxygenase-2 expression is an independent predictor of poor prognosis in colon cancer. Clin Cancer Res 14, 8221-8227.
25.Pasche, B., Wang, M., Pennison, M., Jimenez, H., 2014. Prevention and treatment of cancer with aspirin: where do we stand? Semin Oncol 41, 397-401.
26.Pearce, E.L., Walsh, M.C., Cejas, P.J., Harms, G.M., Shen, H., Wang, L.S., Jones, R.G., Choi, Y., 2009. Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Nature 460, 103-107.
27.Rothwell, P.M., Wilson, M., Elwin, C.E., Norrving, B., Algra, A., Warlow, C.P., Meade, T.W., 2010. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet 376, 1741-1750.
28.Rothwell, P.M., Wilson, M., Price, J.F., Belch, J.F., Meade, T.W., Mehta, Z., 2012. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet 379, 1591-1601.
29.Russell, W.O., Cohen, J., Enzinger, F., Hajdu, S.I., Heise, H., Martin, R.G., Meissner, W., Miller, W.T., Schmitz, R.L., Suit, H.D., 1977. A clinical and pathological staging system for soft tissue sarcomas. Cancer 40, 1562-1570.
30.Sarrouilhe, D., Clarhaut, J., Defamie, N., Mesnil, M., 2015. Serotonin and Cancer: What Is the Link? Curr Mol Med 15, 62-77.
31.Serafeim, A., 2002. 5-Hydroxytryptamine drives apoptosis in biopsylike Burkitt lymphoma cells: reversal by selective serotonin reuptake inhibitors. Blood 99, 2545-2553.
32.Siddiqui, E.J., Shabbir, M.A., Mikhailidis, D.P., Mumtaz, F.H., Thompson, C.S., 2006. The effect of serotonin and serotonin antagonists on bladder cancer cell proliferation. BJU Int 97, 634-639.
33.Takai, D., Yagi, Y., Wakazono, K., Ohishi, N., Morita, Y., Sugimura, T., Ushijima, T., 2001. Silencing of HTR1B and reduced expression of EDN1 in human lung cancers, revealed by methylation-sensitive representational difference analysis. Oncogene 20, 7505-7513.
34.Thompson, A.M., 2014. Molecular pathways: preclinical models and clinical trials with metformin in breast cancer. Clin Cancer Res 20, 2508-2515.
35.Veterinary Co-operative Oncology, G., 2004. Veterinary Co-operative Oncology Group - Common Terminology Criteria for Adverse Events (VCOG-CTCAE) following chemotherapy or biological antineoplastic therapy in dogs and cats v1.0.Vet Comp Oncol 2, 195-213.
36.Vicaut, E., Laemmel, E., Stucker, O., 2000. Impact of serotonin on tumour growth. Ann Med 32, 187-194.
37.Walker, A.J., Grainge, M.J., Card, T.R., 2012. Aspirin and other non-steroidal anti-inflammatory drug use and colorectal cancer survival: a cohort study. Brit J Cancer 107, 1602-1607.
38.Wintrob, Z.A., 2015. Should pharmacokinetic safety challenges prevent metformin use in patients with cancer? J Pharm Pract 28, 48-49.
39.Yasuda, T., Kanamori, M., Nogami, S., Hori, T., Oya, T., Suzuki, K., Kimura, T., 2009. Establishment of a new human osteosarcoma cell line, UTOS-1: cytogenetic characterization by array comparative genomic hybridization. J Exp Clin Cancer Res 28, 26.
40.Zilkha-Falb, R., Ziv, I., Nardi, N., Offen, D., Melamed, E., Barzilai, A., 1997. Monoamine-induced apoptotic neuronal cell death. Cell Mol Neurobiol 17, 101-118.


QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top