請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/62668
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 江俊斌 | |
dc.contributor.author | Wei-Ren Shen | en |
dc.contributor.author | 沈威任 | zh_TW |
dc.date.accessioned | 2021-06-16T16:07:01Z | - |
dc.date.available | 2015-09-24 | |
dc.date.copyright | 2013-09-24 | |
dc.date.issued | 2013 | |
dc.date.submitted | 2013-06-11 | |
dc.identifier.citation | Adriaenssens E, Vanhecke E, Saule P, Mougel A, Page A, Romon R,Nurcombe V, Le Bourhis X, Hondermarck H: Nerve growth factor is a potential therapeutic target in breast cancer. Cancer Res 2008; 68:346-351.
Akert K, Sandri C, Weibel ER, Peper K, Moor H. The fine structure of the perineural endothelium. Cell Tissue Res 1976;165:281-295. Aloe L, Rocco ML, Bianchi P, Manni L. Nerve growth factor: from the early discoveries to the potential clinical use. J Transl Med 2012;10:239. Bapat AA, Hostetter G, Von Hoff DD, Han H. Perineural invasion and associated pain in pancreatic cancer. Nat Rev Cancer 2011; 23;11:695-707. Barrett AW, Speight PM. Perineural invasion in adenoid cystic carcinoma of the salivary glands: a valid prognostic indicator? Oral Oncol 2009;45:936-940 Bergmann F, Ceyhan GO, Rieker RJ, Esposito I, Fischer L, Herpel E, Friess H, Schirmacher P, Kern MA. Fundamental differences in the neural invasion behavior of pancreatic endocrine tumors: relevance for local recurrence rates? Hum Pathol 2009; 40:50-57. Bernier J, Cooper JS. Chemoradiation after surgery for high-risk head and neck cancer patients: how strong is the evidence? Oncologist 2005;10:215-224. Binmadi NO, Basile JR. Perineural invasion in oral squamous cell carcinoma: a discussion of significance and review of the literature. Oral Oncol 2011;47:1005-1010. Brandwein-Gensler M, Teixeira MS, Lewis CM, Lee B, Rolnitzky L, Hille JJ, Genden E, Urken ML, Wang BY. Oral squamous cell carcinoma: histologic risk assessment, but not margin status, is strongly predictive of local disease-free and overall survival. Am J Surg Pathol 2005;29:167-178. Caldemeyer KS, Mathews VP, Righi PD, Smith RR.Imaging features and clinical significance of perineural spread or extension of head and neck tumors. Radiographics 1998;18:97-110. Cantarella G, Lempereur L, Presta M, Ribatti D, Lombardo G, Lazarovici P, Zappalà G, Pafumi C, Bernardini R.Nerve growth factor-endothelial cell interaction leads to angiogenesis in vitro and in vivo. FASEB J 2002;16:1307-1309. Carter BD, Kaltschmidt C, Kaltschmidt B, Offenhäuser N, Böhm-Matthaei R, Baeuerle PA, Barde Y-A. Activation of NF-kB by nerve growth factor through the neurotrophin receptor p75. Science1996; 272: 542-545. Davidson B, Reich R, Lazarovici P, Flørenes VA, Risberg B, Nielsen S, Sert B, Bedrossian C. Expression of the nerve growth factor receptors TrkA and p75 in malignant mesothelioma. Lung Cancer 2004;44:159-165. Dang C, Zhang Y, Ma Q, Shimahara Y. Expression of nerve growth factor receptors is correlated with progression and prognosis of human pancreatic cancer. J Gastroenterol Hepatol 2006;21:850-858 D'Cruz AK, Siddachari RC, Walvekar RR, Pantvaidya GH, Chaukar DA, Deshpande MS, Pai PS, Chaturvedi P. Elective neck dissection for the management of the N0 neck in early cancer of the oral tongue: need for a randomized controlled trial. Head Neck. 2009;31:618-624. Derby A, Engleman VW, Frierdich GE, Neises G, Rapp SR, Roufa DG.Nerve growth factor facilitates regeneration across nerve gaps: morphological and behavioral studies in rat sciatic nerve. Exp Neurol 1993;119:176-191. Dollé JP, Rezvan A, Allen FD, Lazarovici P, Lelkes PI.Nerve growth factor-induced migration of endothelial cells. J Pharmacol Exp Ther 2005;315:1220-1227. Du ZJ, Wang L, Lei DL, Liu BL, Cao J, Zhang P, Ma Q. Nerve growth factor injected systemically improves the recovery of the inferior alveolar nerve in a rabbit model of mandibular distraction osteogenesis. Br J Oral Maxillofac Surg 2011;49:557-561. Duraker N, Caynak ZC, Türköz K. Perineural invasion has no prognostic value in patients with invasive breast carcinoma. Breast 2006;15:629-634. Egeblad, M., and Werb, Z. New functions for the matrix metalloproteinases. in cancer progression. Nat Rev Cancer 2002; 2: 161-174. Fagan JJ, Collins B, Barnes L, D'Amico F, Myers EN, Johnson JT. Perineural invasion in squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg 1998;124:637-640. Fahed Samir Habash, Ra’ed O Abu Hantash,1 and Mohammed Abu Yunis. Assessment of the innervation pattern of oral squamous cell carcinoma using neural protein gene product (9.5)–An immunocytochemical study. J Oral Maxillofac Pathol 2012;16:16-21. Fukano H, Matsuura H, Hasegawa Y, Nakamura S.Depth of invasion as a predictive factor for cervical lymph node metastasis in tongue carcinoma. Head Neck 1997;19:205-210. Gandour-Edwards R, Kapadia S, Barnes L, Donald P, Janecka IP. Neural cell adhesion molecule in adenoid cystic carcinoma invading the skull base. Otolaryngol Head Neck Surg 1997;117:453-458. Geldof AA, De Kleijn MA, Rao BR, Newling DW. Nerve growth factor stimulates in vitro invasive capacity of DU145 human prostatic cancer cells. J Cancer Res Clin Oncol 1997;123:107-12. Gil Z, Carlson DL, Gupta A, Lee N, Hoppe B, Shah JP, Kraus DH. Patterns and incidence of neural invasion in patients with cancers of the paranasal sinuses. Arch Otolaryngol Head Neck Surg 2009;135:173-179. Goepfert H, Dichtel WJ, Medina JE, Lindberg RD, Luna MD. Perineural invasion in squamous cell skin carcinoma of the head and neck. Am J Surg 1984;148:542-547. Haifeng Jin, Yanglin Pan, Lina Zhao, Huihong Zhai, Xiaohua Li, Li Sun, Lijie He, Yu Chen, Liu Hong, Yulei Du, and Daiming Fan. p75 Neurotrophin Receptor Suppresses the Proliferation of Human Gastric Cancer Cells. Neoplasia 2007;9:471-478. Inoue M, Roan CH, Abe T, Buery RR, Nagatsuka H, Katase N, Nagai N, Setsu K. Localization and characterization of lymphatic vessels in oral and cervical squamous cell carcinoma. Exp Ther Med 2011;2:793-797. Jackson JE, Dickie GJ, Wiltshire KL, Keller J, Tripcony L, Poulsen MG, Hughes M, Allison RW, Martin JM. Radiotherapy for perineural invasion in cutaneous head and neck carcinomas: toward a risk-adapted treatment approach. Head Neck 2009;31:604-610. Ji RR, Samad TA, Jin SX, Schmoll R, Woolf CJ. p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron 2002;36:57-68. Jin H, Pan Y, He L, Zhai H, Li X, Zhao L, Sun L, Liu J, Hong L, Song J, Xie H, Gao J, Han S, Li Y, Fan D.p75 neurotrophin receptor inhibits invasion and metastasis of gastric cancer. Mol Cancer Res 2007;5:423-433. Julio-Pieper M, Lara HE, Bravo JA, Romero C.Effects of nerve growth factor (NGF) on blood vessels area and expression of the angiogenic factors VEGF and TGFbeta1 in the rat ovary. Reprod Biol Endocrinol 2006;4:57. Karak SG, Quatrano N, Buckley J, Ricci A Jr.Prevalence and significance of perineural invasion in invasive breast carcinoma. Conn Med. 2010;74:17-21. Kolokythas A, Cox DP, Dekker N, Schmidt BL.Nerve growth factor and tyrosine kinase A receptor in oral squamous cell carcinoma: is there an association with perineural invasion? J Oral Maxillofac Surg 2010;68:1290-1295. Kurtz KA, Hoffman HT, Zimmerman MB, Robinson RA. Perineural and vascular invasion in oral cavity squamous carcinoma: increased incidence on re-review of slides and by using immunohistochemical enhancement. Arch Pathol Lab Med 2005;129:354-359. Lagadec C, Meignan S, Adriaenssens E, Foveau B, Vanhecke E, Romon R, Toillon RA, Oxombre B, Hondermarck H, Le Bourhis X: TrkA overexpression enhances growth and metastasis of breast cancer cells. Oncogene 2009;28:1960-1970. Levi-Montalcini R. The nerve growth factor: thirty-five years later. Science 1987;237:1154-1162. Liebig C, Ayala G, Wilks J, Verstovsek G, Liu H, Agarwal N, Berger DH, Albo D.Perineural invasion is an independent predictor of outcome in colorectal cancer. J Clin Oncol 2009;27:5131-5137. Liebig C, Ayala G, Wilks JA, Berger DH, Albo D. Perineural invasion in cancer: a review of the literature. Cancer 2009;115:3379-3391. Mendenhall WM, Parsons JT, Mendenhall NP, Brant TA, Stringer SP, Cassisi NJ, Million RR. Carcinoma of the skin of the head and neck with perineural invasion. Head Neck 2002;24:78-83. Michikawa C, Uzawa N, Kayamori K, Sonoda I, Ohyama Y, Okada N, Yamaguchi A, Amagasa T. Clinical significance of lymphatic and blood vessel invasion in oral tongue squamous cell carcinomas. Oral Oncol 2012;48:320-324. Miknyoczki SJ, Wan W, Chang H, Dobrzanski P, Ruggeri BA, Dionne CA, Buchkovich K. The neurotrophin-trk receptor axes are critical for the growth and progression of human prostatic carcinoma and pancreatic ductal adenocarcinoma xenografts in nude mice. Clin Cancer Res 2002;8:1924-1931. National Cancer Institute. Surveillance, Epidemiology, and End Results (SEER) web site. http://seer.cancer.gov/statistics. Niamh H. Molloy, Danielle E. Read and Adrienne M. Gorman. Review Nerve Growth Factor in Cancer Cell Death and Survival. Cancers 2011;3:510-530. Nico B, Mangieri D, Benagiano V, Crivellato E, Ribatti D.Nerve growth factor as an angiogenic factor. Microvasc Res 2008;75:135-141. Niewiadomska G, Mietelska-Porowska A, Mazurkiewicz M. The cholinergic system, nerve growth factor and the cytoskeleton. Behav Brain Res 2011;221:515-526. O-charoenrat P, Pillai G, Patel S, Fisher C, Archer D, Eccles S, Rhys-Evans P. Tumour thickness predicts cervical nodal metastases and survival in early oral tongue cancer. Oral Oncol 2003;39:386-390. Okada Y. Relationships of cervical lymph node metastasis to histopathological malignancy grade, tumor angiogenesis, and lymphatic invasion in tongue cancer. Odontology 2010;98:153-159. Okada Y, Eibl G, Guha S, Duffy JP, Reber HA, Hines OJ.Nerve growth factor stimulates MMP-2 expression and activity and increases invasion by human pancreatic cancer cells. Clin Exp Metastasis 2004;21:285-292. Park HJ, Kim MN, Kim JG, Bae YH, Bae MK, Wee HJ, Kim TW, Kim BS, Kim JB, Bae SK, Yoon S.Up-regulation of VEGF expression by NGF that enhances reparative angiogenesis during thymic regeneration in adult rat. Biochim Biophys Acta 2007;1773:1462-1472. Park MJ, Kwak HJ, Lee HC, Yoo DH, Park IC, Kim MS, Lee SH, Rhee CH, Hong SI. Nerve growth factor induces endothelial cell invasion and cord formation by promoting matrix metalloproteinase-2 expression through the phosphatidylinositol 3-kinase/Akt signaling pathway and AP-2 transcription factor. J Biol Chem 2007;282:30485-30496. Patapoutian A, Reichardt LF.Trk receptors: mediators of neurotrophin action. Curr Opin Neurobiol 2001;11:272-280. Patricia Harnden, Michael D. Shelley, Hayley Clements, Bernadette Coles, R. Sandy Tyndale-Biscoe, Brian Naylor, Malcolm D. Mason. The prognostic significance of perineural invasion in prostatic Cancer Biopsies. Cancer 2007;109:13-24. Pentenero M, Gandolfo S, Carrozzo M. Importance of tumor thickness and depth of invasion in nodal involvement and prognosis of oral squamous cell carcinoma: a review of the literature. Head Neck 2005;27:1080-1091. Poeschl EM, Pollheimer MJ, Kornprat P, Lindtner RA, Schlemmer A, Rehak P, Vieth M, Langner C.Perineural invasion: correlation with aggressive phenotype and independent prognostic variable in both colon and rectum cancer. J Clin Oncol 2010;28:358-360. Rahima B, Shingaki S, Nagata M, Saito C.Prognostic significance of perineural invasion in oral and oropharyngeal carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004;97:423-431. Ricci A, Greco S, Mariotta S, Felici L, Bronzetti E, Cavazzana A, Cardillo G, Amenta F, Bisetti A, Barbolini G. Neurotrophins and neurotrophin receptors in human lung cancer. Am J Respir Cell Mol Biol 2001;25:439-446. RL Cater, CS Foster, Elizabeth A Dinsdale, MR Pittam. Penrneural spread by squamous carcinomas of the head and neck: a morphological study using antiaxonal and antimyelin monoclonal antibodies. J Clin Pathol 1983;36:269-275. Rocha AS, Risberg B, Magalhães J, Trovisco V, de Castro IV, Lazarovici P, Soares P, Davidson B, Sobrinho-Simões M.The p75 neurotrophin receptor is widely expressed in conventional papillary thyroid carcinoma. Hum Pathol 2006;37:562-568. Romon R, Adriaenssens E, Lagadec C, Germain E, Hondermarck H, Le Bourhis X. Nerve growth factor promotes breast cancer angiogenesis by activating multiple pathways. Mol Cancer 2010;9:157. Ross GL, Soutar DS, MacDonald GD, et al. Sentinel node biopsy in head and neck cancer: preliminary results of a multicenter trial. Ann Surg Oncol 2004;11:690-696 Rukwied R, Mayer A, Kluschina O, Obreja O, Schley M, Schmelz M.NGF induces non-inflammatory localized and lasting mechanical and thermal hypersensitivity in human skin. Pain. 2010;148:407-413. Sakamoto Y, Kitajima Y, Edakuni G, Hamamoto T, Miyazaki K. Combined evaluation of NGF and p75NGFR expression is a biomarker for predicting prognosis in human invasive ductal breast carcinoma. Oncol Rep 2001;8:973-980. Sethi S, Lu M, Kapke A, Benninger MS, Worsham MJ. Patient and tumor factors at diagnosis in a multi-ethnic primary head and neck squamous cell carcinoma cohort. J Surg Oncol 2009 ;99:104-108. Shen FZ, Zhang BY, Feng YJ, Jia ZX, An B, Liu CC, Deng XY, Kulkarni AD, Lu Y. Current research in perineural invasion of cholangiocarcinoma. J Exp Clin Cancer Res 2010;29:24. Shyh-Kuan Tai, Wing-Yin Li, Pen-Yuan Chu, Shyue-Yih Chang, Tung-Lung Tsai, Yi-Fen Wang, Jui-Lin Huang. Risks and clinical implications of perineural invasion in T1-2 oral tongue squamous cell carcinoma. Head Neck 2012;34:994-1001. Simone MD, De Santis S, Vigneti E, Papa G, Amadori S, Aloe L. Nerve growth factor: a survey of activity on immune and hematopoietic cells. Hematol Oncol 1999;17:1-10. Soo-youn An,Eun-Jung Jung, Myungchul Lee, Tack-Kyun Kwon, Myung-Whun Sung, Yoon Kyung Jeon, Kwang Hyun Kim. Factors Related to Regional Recurrence in Early Stage Squamous Cell Carcinoma of the Oral Tongue. Clin Exp Otorhinolaryngol 2008;1: 166-170. Søland TM, Brusevold IJ, Koppang HS, Schenck K, Bryne M. Nerve growth factor receptor (p75 NTR) and pattern of invasion predict poor prognosis in oral squamous cell carcinoma. Histopathology 2008;53:62-72. Spector JG, Lee P, Derby A, Frierdich GE, Neises G, Roufa DG.Rabbit facial nerve regeneration in NGF-containing silastic tubes. Laryngoscope 1993;103:548-558. Sullivan LM, Smee R. Leptomeningeal carcinomatosis from perineural invasion of a lip squamous cell carcinoma. Australas Radiol 2006;50:262-266. Svensson P, Wang K, Arendt-Nielsen L, Cairns BE.Effects of NGF-induced muscle sensitization on proprioception and nociception. Exp Brain Res 2008;189:1-10. Tai SK, Li WY, Chu PY, Chang SY, Tsai TL, Wang YF, Huang JL.Risks and clinical implications of perineural invasion in T1-2 oral tongue squamous cell carcinoma. Head Neck 2012;34:994-1001. Tsunoda S, Okumura T, Ito T, Mori Y, Soma T, Watanabe G, Kaganoi J, Itami A, Sakai Y, Shimada Y. Significance of nerve growth factor overexpression and its autocrine loop in oesophageal squamous cell carcinoma. Br J Cancer 2006;95:322-330. Wang L, Cao J, Lei DL, Cheng XB, Yang YW, Hou R, Zhao YH, Cui FZ. Effects of nerve growth factor delivery via a gel to inferior alveolar nerve in mandibular distraction osteogenesis. J Craniofac Surg 2009;20:2188-92. Wang L, Sun M, Jiang Y, Yang L, Lei D, Lu C, Zhao Y, Zhang P, Yang Y, Li J. Nerve growth factor and tyrosine kinase A in human salivary adenoid cystic carcinoma: expression patterns and effects on in vitro invasive behavior. J Oral Maxillofac Surg 2006;64:636-641. Warrington RJ, Lewis KE. Natural antibodies against nerve growth factor inhibit in vitro prostate cancer cell metastasis. Cancer Immunol Immunother 2011;60:187-195. Wu XY, Tong DD, Zhang FH. Expression and significance of P75 neurotrophin receptor in oral squamous cell carcinoma. Shanghai Kou Qiang Yi Xue. 2011;20:405-408. Xue Q, Jong B, Chen T, Schumacher MA. Transcription of rat TRPV1 utilizes a dual promoter system that is positively regulated by nerve growth factor. J Neurochem 2007;101:212-222. Young C, Miller E, Nicklous DM, Hoffman JR. Nerve growth factor and neurotrophin-3 affect functional recovery following peripheral nerve injury differently. Restor Neurol Neurosci 2001;18:167-175. Yang G, Wheeler TM, Kattan MW, Scardino PT, Thompson TC. Perineural invasion of prostate carcinoma cells is associated with reduced apoptotic index. Cancer 1996;78:1267-1271. Ye Y, Dang D, Zhang J, Viet CT, Lam DK, Dolan JC, Gibbs JL, Schmidt BL. Nerve Growth Factor Links Oral Cancer Progression,Pain, and Cachexia. Mol Cancer Ther 2011;10:1667-1676. Yu EH, Lui MT, Tu HF, Wu CH, Lo WL, Yang CC, Chang KW, Kao SY. Oral carcinoma with perineural invasion has higher nerve growth factor expression and worse prognosis. Oral Dis 2013;10:1-7. Zhu Z, Friess H, diMola FF, Zimmermann A, Graber HU, Korc M, Büchler MW.Nerve growth factor expression correlates with perineural invasion and pain in human pancreatic cancer. J Clin Oncol 1999;17:2419-2428. Zhu Z, Kleeff J, Kayed H, Wang L, Korc M, Büchler MW, Friess H. Nerve growth factor and enhancement of proliferation, invasion, and tumorigenicity of pancreatic cancer cells. Mol Carcinog 2002 ;35:138-147. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/62668 | - |
dc.description.abstract | 背景:
神經侵犯常見於舌鱗狀細胞癌。過去研究顯示神經侵犯不論在神經親合性高或低的腫瘤,都可以預測癌症患者的預後。神經生長因子(NGF)是促進神經侵犯的可能因子之一,並且它與癌細胞的增生、血管生成和基質破壞有關。 方法: 研究對象為116例T1-T4舌鱗狀細胞癌。重新覆閱hematoxylin & eosin染色切片並先進行S-100免疫染色,偵測顯微鏡下潛在的神經侵犯病灶、數目,舌鱗狀細胞癌切片同時進行NGF免疫染色。 結果: 重新觀察hematoxylin & eosin染色切片尋找潛在的神經侵犯病灶,神經侵犯陽性病例的比率由21%有效提升至38%;之後在S-100免疫染色切片輔助下,陽性比率再提至51%。藉由多變數分析,腫瘤厚度高於5 mm (p = 0.003) 和腫瘤最高侵犯端形式(WPOI)等級4以上(p = 0.001) 與神經侵犯的存在相關。Kaplan-Meier存活曲線分析,神經侵犯陽性病例比起神經侵犯陰性病例,有較差的整體存活率 (log-rank test, p = 0.0352)。高神經親合性的腫瘤(神經內侵犯、高於三個神經侵犯病灶、神經侵犯病灶直徑大於0.2 mm),其NGF標定分數會比低神經親合性腫瘤(無神經內侵犯、一至三個神經侵犯病灶、神經侵犯病灶直徑0.2 mm以下)來得高。此外,在單變數分析,較高的T 分期或N 分級、較高的腫瘤厚度、鄰近或是陽性的腫瘤切除邊緣和神經侵犯陽性都與NGF高度表現相關,然而多變數分析之後,只剩下T 分期能夠預測NGF表現強度。Kaplan-Meier存活曲線分析,NGF高度表現的病例比起NGF低度表現病例,有較差的整體存活率(log-rank test, p = 0.0292)。 結論: 謹慎地重新觀察hematoxylin & eosin或是進行S-100免疫染色切片,能有效偵測腫瘤組織內潛在的神經侵犯病灶。腫瘤厚度超過5 mm以及腫瘤侵犯端過於分散表示舌鱗狀細胞癌很有可能有神經侵犯存在。NGF標定分數與舌鱗狀細胞癌的神經親合性有正向關係。腫瘤水平長度是NGF於舌鱗狀細胞癌細胞表現的獨立預測因子。神經侵犯和NGF表現強度,可以預測舌鱗狀細胞癌患者的預後。 | zh_TW |
dc.description.abstract | Background: Perineural invasion (PNI) is commonly seen in oral tongue squamous cell carcinoma (OTSCC). PNI can predict the prognosis in malignancies of low or high neurotropism. Nerve growth factor (NGF), a potential neurotropic factor promoting the PNI, is associated with tumor cell proliferation, angiogenesis, and stromal destruction.
Methods: PNI was detected by reevaluation of H&E-stained and anti-S-100 immunostained tissue sections in 116 T1 to T4 OTSCC specimens. Immunohistochemical staining for nerve growth factor (NGF) was also performed in these 116 OTSCC cases. Results: The PNI rate increased from 22% of the original report, through 38% after reevaluation of H&E-stained tissue sections, to 51% with the help of anti-S-100 immunostaining. Univariate analyses showed a significant association of the presence of PNI with higher T status or N status, greater tumor thickness, close and positive tumor section margin, and higher grade of worst pattern of invasion (WPOI). Tumor thickness (p = 0.003) and WPOI (p = 0.001) were identified as independent predictors for the PNI by multivariate analyses. OTSCC patients with PNI had a poorer overall survival than those without PNI (log-rank test, p = 0.0352). OTSCCs with higher neurotrposim (intraneural spread, >3 PNI foci in each tissue section, and PNI focus diameter > 0.2 mm) demonstrated higher NGF labeling score than those with lower neurotropism (non-intraneural spread, 1-3 PNI foci in each tissue section, and PNI focus diameter ≤ 0.2 mm). Moreover, higher NGF expression level in OTSCCs had a significant and positive relation to higher T status or N status, greater tumor thickness, close and positive tumor section margin, and the presence of PNI by univariate analyses. However, only higher T status (p = 0.047) was identified as an independent factor for prediction of NGF expression level by multivariate analyses. In addition, OTSCC patients with high NGF expression level exhibited poorer overall survival than those with low NGF expression level (log-rank test, p = 0.0292). Conclusion: Cautious reevaluation of H&E-stained and anti-S-100 immunostained tissue sections is an effective method to detect occult PNI. Tumor thickness greater than 5 mm and markedly discrete invasion front pattern are two important factors to predict the presence of PNI. NGF expression level has a positive relation to neurotropism of OTSCCs. Horizontal tumor dimension is an independent predictor for NGF expression level in OTSCCs. Both PNI and NGF expression level can predict the prognosis of OTSCC patients. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T16:07:01Z (GMT). No. of bitstreams: 1 ntu-102-R00422001-1.pdf: 1602754 bytes, checksum: 5e0bb5b4960845ec40eb25e233b818d5 (MD5) Previous issue date: 2013 | en |
dc.description.tableofcontents | 口試委員審定書..................................i
致謝............................................ii Abstract........................................iii 中文摘要........................................v Chapter 1. Literature review....................1 1.1 Oral tongue squamous cell carcinoma.........1 1.1.1 Epidemiology........................1 1.1.2 Clinical features of OTSCC..........1 1.2 Perineural invasion.........................2 1.2.1 Perineural invasion: A third form of cancer metastasis......................................2 1.2.2 Histological patterns of PNI........3 1.2.3 Clinical significance of PNI........4 1.3 Nerve growth factor.........................6 1.3.1 Neurotrophins and perineural invasion......6 1.3.2 Biological functions of NGF.........7 1.3.3 Expression of NGF and its receptors in malignancies....................................9 1.3.4 Neural cell adhesion molecule.......10 1.3.5 Effects of NGF on cancer cell lines..10 Chapter 2. Purpose of this study................12 Chapter 3. Materials and methods................13 3.1 Collection of clinicopathological information......13 3.2 Review of slides............................13 3.3 Immunohistochemistry........................16 3.4 Quantification of immuno-stained NGF-positive cells...16 3.5 Statistical Analysis........................17 Chapter 4. Results..............................18 4.1 Detection of occult perineural invasion.....18 4.2 Clinicopathological factors and perineural invasion...18 4.3 Comparison of mean NGF labeling score.......19 4.4 Clinicopathological factors and NGF expression level..20 4.5 Survival analysis...........................21 Chapter 5. Discussion...........................22 Chapter 6. Conclusion...........................28 Reference.......................................29 Table 1. Incidence of perineural invasion in different malignancies....................................38 Table 2. Clinicopathological features of 116 OTSCC patients .......................................39 Table 3. Data of 59 PNI-positive cases..........40 Table 4. Univariate and multivariate analysis between PNI and clinicopathological parameters..........41 Table 5. Comparison of NGF labeling score between PNI-positive and -negative groups...................42 Table 6. Comparison of NGF labeling score between PNI-positive subgroups..............................43 Table 7. Association of NGF expression level with clinicopathological parameters by univariate and multivariate analyses...........................44 Table 8. Clinicopathological features of 83 OTSCC patients for survival analysis...........................45 Figure 1. Changes of PNI rate in different experimental stages..........................................46 Figure 2. Occult PNI foci revealed by anti-S-100 immunostaining..................................47 Figure 3. PNI rate and tumor thickness ..........48 Figure 4. PNI rate and worst pattern of invasion......49 Figure 5. Photogragphs of H&E-stained, anti-100 immunostained, and anti-nerve growth factor immunostained tissue sections.................................50 Figure 6. Mean NGF labeling scores (LS) of subgroups categorized by the pattern of PNI...............52 Figure 7. Mean NGF labeling score (LS) of subgroups categorized by the diameter of PNI focus........53 Figure 8. Mean NGF labeling score (LS) of subgroups categorized by the number of PNI focus in each tissue section.........................................54 Figure 9. Mean NGF labeling score (LS) and T stage.....55 Figure 10. Kaplan-Meier survival curves for PNI-positive and PNI-negative patients........................56 Figure 11. Kaplan-Meier survival curves for high NGF expression level group and low NGF expression level group...........................................57 | |
dc.language.iso | en | |
dc.title | 舌鱗狀細胞癌的神經侵犯與神經生長因子表現 | zh_TW |
dc.title | Perineural invasion and expression of nerve growth factor in oral tongue squamous cell carcinoma | en |
dc.type | Thesis | |
dc.date.schoolyear | 101-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 張龍昌,靳應臺 | |
dc.subject.keyword | 口腔,舌,鱗狀細胞癌,神經侵犯,神經生長因子, | zh_TW |
dc.subject.keyword | oral,tongue,squmamous cell carcinoma,perineural invasion,nerve growth factor, | en |
dc.relation.page | 57 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2013-06-13 | |
dc.contributor.author-college | 牙醫專業學院 | zh_TW |
dc.contributor.author-dept | 臨床牙醫學研究所 | zh_TW |
顯示於系所單位: | 臨床牙醫學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-102-1.pdf 目前未授權公開取用 | 1.57 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。