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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 李繼忠 | |
dc.contributor.author | Hui-Wen Ho | en |
dc.contributor.author | 何卉文 | zh_TW |
dc.date.accessioned | 2021-06-16T10:28:14Z | - |
dc.date.available | 2018-08-26 | |
dc.date.copyright | 2013-08-26 | |
dc.date.issued | 2013 | |
dc.date.submitted | 2013-08-15 | |
dc.identifier.citation | 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.
Bianco, R., Melisi, D., Ciardiello, F., Tortora, G., 2006. Key cancer cell signal transduction pathways as therapeutic targets. European journal of cancer 42, 290-294. Bojkova, B., Orendas, P., Garajova, M., Kassayova, M., Kutna, V., Ahlersova, E., Ahlers, I., 2009. Metformin in chemically-induced mammary carcinogenesis in rats. Neoplasma 56, 269. Bowker, S.L., Majumdar, S.R., Veugelers, P., Johnson, J.A., 2006. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes care 29, 254-258. Cantrell, L.A., Zhou, C., Mendivil, A., Malloy, K.M., Gehrig, P.A., Bae-Jump, V.L., 2010. Metformin is a potent inhibitor of endometrial cancer cell proliferation—implications for a novel treatment strategy. Gynecologic oncology 116, 92-98. Currie, C., Poole, C., Gale, E., 2009. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia 52, 1766-1777. Eisenhauer, E., Therasse, P., Bogaerts, J., Schwartz, L., Sargent, D., Ford, R., Dancey, J., Arbuck, S., Gwyther, S., Mooney, M., 2009. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). European journal of cancer 45, 228-247. Endo, M., Tateishi, U., Seki, K., Yamaguchi, U., Nakatani, F., Kawai, A., Chuman, H., Beppu, Y., 2007. Prognostic implications of glucose transporter protein-1 (glut-1) overexpression in bone and soft-tissue sarcomas. Japanese journal of clinical oncology 37, 955-960. Group, V.C.O., 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, 194-213. Heller, J.B., 2007. Metformin overdose in dogs and cats. VETERINARY MEDICINE-BONNER SPRINGS THEN EDWARDSVILLE- 102, 231. Henry, C.J., Higginbotham, M.L., 2009. Cancer management in small animal practice. Saunders. Jiralerspong, S., Palla, S.L., Giordano, S.H., Meric-Bernstam, F., Liedtke, C., Barnett, C.M., Hsu, L., Hung, M.-C., Hortobagyi, G.N., Gonzalez-Angulo, A.M., 2009. Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. Journal of Clinical Oncology 27, 3297-3302. Joyce, J.A., 2005. Therapeutic targeting of the tumor microenvironment. Cancer cell 7, 513. Kunkel, M., Reichert, T.E., Benz, P., Lehr, H.A., Jeong, J.H., Wieand, S., Bartenstein, P., Wagner, W., Whiteside, T.L., 2003. Overexpression of Glut‐1 and increased glucose metabolism in tumors are associated with a poor prognosis in patients with oral squamous cell carcinoma. Cancer 97, 1015-1024. Kuntz, C., Dernell, W., Powers, B., Devitt, C., Straw, R., Withrow, S., 1997. Prognostic factors for surgical treatment of soft-tissue sarcomas in dogs: 75 cases (1986-1996). Journal of the American Veterinary Medical Association 211, 1147. 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. 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. Lund, S.S., Tarnow, L., Stehouwer, C.D., Schalkwijk, C.G., Teerlink, T., Gram, J., Winther, K., Frandsen, M., Smidt, U.M., Pedersen, O., 2008. Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes. European Journal of Endocrinology 158, 631-641. Maddison, J.E., Page, S.W., 2008. Small animal clinical pharmacology. Saunders Limited. Oliveras-Ferraros, C., Vazquez-Martin, A., Menendez, J.A., 2009. Genome-wide inhibitory impact of the AMPK activator metformin on [kinesins, tubulins, histones, auroras and polo-like kinases] M-phase cell cycle genes in human breast cancer cells. Cell Cycle 8, 1633-1636. Plumb, D.C., 2005. Plumb's veterinary drug handbook. PharmaVet. Pollak, M., 2008. Insulin and insulin-like growth factor signalling in neoplasia. Nature Reviews Cancer 8, 915-928. Sahra, I.B., 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. Thoreen, C.C., Sabatini, D.M., 2005. AMPK and p53 help cells through lean times. Cell Metabolism 1, 287-288. Tomlinson, J., Barsky, S.H., Nelson, S., Singer, S., Pezeshki, B., Lee, M.C., Eilber, F., Nguyen, M., 1999. Different patterns of angiogenesis in sarcomas and carcinomas. Clinical Cancer Research 5, 3516-3522. Vitale-Cross, L., Molinolo, A.A., Martin, D., Younis, R.H., Maruyama, T., Patel, V., Chen, W., Schneider, A., Gutkind, J.S., 2012. Metformin prevents the development of oral squamous cell carcinomas from carcinogen-induced premalignant lesions. Cancer Prevention Research 5, 562-573. Zakikhani, M., Dowling, R., Fantus, I.G., Sonenberg, N., Pollak, M., 2006. Metformin is an AMP kinase–dependent growth inhibitor for breast cancer cells. Cancer research 66, 10269-10273. Zhuang, Y., Miskimins, W.K., 2011. Metformin induces both caspase-dependent and poly (ADP-ribose) polymerase-dependent cell death in breast cancer cells. Molecular Cancer Research 9, 603-615. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/60741 | - |
dc.description.abstract | 目前腫瘤占犬貓死亡原因的前十位,癌症治療仍有許多課題需要探討與研究。癌症始終具有極高的致死率,而致死原因不外乎癌症治療的限制及其他影響飼主積極治療意願的原因,例如化療與放射線治療的副作用、腫塊位置或大小影響手術邊界等等。而針對腫瘤的新穎療法正是當前熱門的治療方向,從腫瘤的發生與分化引導我們研發出新穎的藥物來治療腫瘤,因此對抗腫瘤的專一性提高且副作用降低。在此初探性研究中,我們以腫瘤內注射的方式給予ON B10藥物,來提高腫瘤內的藥物濃度,進而探討ON B10的治療效果,主要評估腫塊的消退率與疾病進展空窗期的長短。ON B10為每福敏、阿斯匹靈與血清素的複合藥劑。最終完成試驗的有15頭患有至少一個皮膚腫塊的犬隻,其中5頭為肉瘤類腫瘤,7頭為上皮類腫瘤,另有3頭則分別不屬於上述兩類的腫瘤。就目前初探性研究的結果來說,腫瘤的消退率平均可達35%;整體而言,又以上皮類腫瘤的反應較佳,可達72%。藥物的副作用則少見,可見有皮膚、消化道、神經、呼吸道及腫瘤疼痛等,評估方式依照獸醫癌症協會分級為準則,程度一與程度二的副作用分別占61%與18.8%,大部分為自限性的輕微不適。研究結果顯示藥物ON B10對於治療皮膚型腫瘤成效不錯且副作用低,日後相關研究則須著重於上皮類腫瘤,以期能在臨床上廣泛運用。 | zh_TW |
dc.description.abstract | Cancer is one of the most important diseases that possess high mortality. Numerous attempts of novel therapeutic trials against tumor cells are still under extensive research investigation. Studies of carcinogenesis and tumor proliferation in molecular level are helpful for novel therapy advancement. Now we are using a combination of antitumor medications to inhibit tumor growth and induce tumor cell death. In this pilot study, the agent named ON B10 was injected intratumorally in order to allow high concentration built up inside the tumor mass and inducing greater tumor killing efficacy. It is important to assess tumor burden volume change which is a valid indicator of the treatment efficacy. In this study, we documented tumor shrinkage rate and disease progression-free interval as an indication of the endpoint of this clinical trial. Fifteen canine patients were enrolled in this study, including soft tissue sarcoma (5), epithelial cell origin tumor (7) and tumors of undetermined origin (3). The expected tumor volume reduction was shown in ten of the patients. Overall reduction rate was 35% and the most promising effect was noted in carcinoma group with average 72% tumor reduction rate. The toxicity was recorded and evaluated in five categories, including dermatologic, gastrointestinal, neurologic, respiratory and tumor pain reactions according to VCOG criteria. The administration of B10 formulation had induced mild toxicities in twelve patients that are all tolerable and self-limited (grade I, 61%; grade II, 18.8%). The results suggest this product can be used to inhibit tumor growth in clinical setting safely and warrant further study focused on carcinomas. Multiple factors affecting drug delivery and tumor responses are discussed. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T10:28:14Z (GMT). No. of bitstreams: 1 ntu-102-R99643012-1.pdf: 1398179 bytes, checksum: bbe345b04c40ce802a0091154b744ca9 (MD5) Previous issue date: 2013 | en |
dc.description.tableofcontents | 口試委員會審定書 i
謝辭 ii 中文摘要 iii Abstract iv Chapter I Introduction 1 1.1 Background of metformin 3 1.2 Preclinical studies of ON B10 4 1.3 Clinical use of ON B10 formulation 4 1.3.1 clinical use of metformin 4 1.3.2 clinical use of aspirin 5 1.3.3 clinical use of serotonin 5 1.4 Pharmacology of these three combination drugs 5 1.4.1 Metformin 5 1.4.2 Aspirin 6 1.4.3 Serotonin 7 1.5 Adverse effect of these three combination drugs 7 1.5.1 Metformin 7 1.5.2 Aspirin 8 1.5.3 Serotonin 8 Chapter II Aim 9 Chapter III Material and method 11 3.1 Study population 12 3.2 Initial evaluation 12 3.3 Treatment protocol 13 3.4 Assessment of response 14 3.5 Side effect 15 3.6 Statistical analysis 16 Chapter IV Result 18 4.1 Animal population 19 4.1.1 Characteristics 19 4.1.2 Clinical staging 19 4.1.3 Pathological grading 20 4.2 Response and variable factors evaluation 20 4.2.1 Response between three tumor types 21 4.2.2 Clinical staging 22 4.2.3 Pathological grading 23 4.3 Side effect 24 Chapter V Discussion 25 5.1 Efficacy 26 5.2 Variable factors evaluation 27 5.3 Microscopic change interpretation 29 5.4 Side effect 30 5.5 Limitations in this study 31 Chapter VI Conclusion 33 Tables and figures 35 Reference 63 | |
dc.language.iso | en | |
dc.title | 以注射抗腫瘤因子抑制腫瘤生長之試驗性研究 | zh_TW |
dc.title | Clinical Trial in Intratumoral Injecting Anti-tumor Drug (ON B10) to Cancer Patients: Pilot Study | en |
dc.type | Thesis | |
dc.date.schoolyear | 101-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 詹東榮,林辰栖,廖泰慶,蕭宏昇 | |
dc.subject.keyword | 每福敏,腫瘤內注射, | zh_TW |
dc.subject.keyword | metformin,intratumoral injection, | en |
dc.relation.page | 65 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2013-08-15 | |
dc.contributor.author-college | 獸醫專業學院 | zh_TW |
dc.contributor.author-dept | 臨床動物醫學研究所 | zh_TW |
顯示於系所單位: | 臨床動物醫學研究所 |
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