眼睑皮肤恶性黑色素瘤早期检测进展(2)

由于实体瘤没有特异性的肿瘤抗原，car-t细胞难以向实体瘤迁移和实体瘤内肿瘤微环境中存在着大量的免疫抑制因子和免疫抑制细胞，因此靶向实体瘤比血液瘤更具难度和挑战性。现认为hsp具有伴移抗原肽的作用，肿瘤组织中提出的hsp-肽复合物可以作为肿瘤排斥抗原，诱导肿瘤特异性免疫，产生特异细胞毒性t细胞（ctl），特异性杀死肿瘤细胞，而且这种作用在同种间不受mhcⅠ类分子限制，这些为肿瘤疫苗的开发提供了新的思路。 鉴于ad．mda-7安全有效的治疗效果和mda．7蛋白对黑素瘤的负性调节作用及其增加肿瘤细胞对化疗敏感性的特点，本实验构建了a375黑素瘤细胞裸鼠移植瘤模型，研究ad．mda-7和dtic联合应用对黑素瘤生长的抑制情况及机制，为探索治疗黑素瘤的新方法提供实验依据。

5展望与问题

因眼睑皮肤恶黑瘤发展迅速，易广泛转移，恶性度高，治疗棘手。早期诊断，及时正确治疗非常重要，建议对于疑似恶黑瘤的眼睑病变均应早期行活组织病检，但因眼睑皮肤恶黑瘤组织结构，细胞形态变化多样，凭临床及病理特征诊断仍有一定困难，因此对其应用

1尹香利,张国昌. BRAF原癌基因与甲状腺癌关系的研究进展.陕西医学杂志,2006;35(3):324-327

2 Collisson EA, De A, Suzuki H, Gambhir SS, Kolodney MS. Treatment of metastatic melanoma with an orally available inhibitor of the Ras-Raf-MAPK cascade. Cancer Research ,2003;63(18):5669-5673

3 Smalley KS. A pivotal role for ERK in malignant melanoma. Int J Cancer,2003; 104(5):527-532

101. lingling zhang, jun li, qin wang, rencheng tong,yuejin zhang, xingsen li, study on relationship between erp logic and direct consume coefficient of i/o table, research and practical issues of enterprise information systemsⅡvolume 1, eds. l. xu, tjoa a. chaudhry s. (boston: springer), pp. 145-152. (istp)。100. lingling zhang, jun li, qin wang, rencheng tong, yuejin zhang, xingsen li, study on relationship between erp logic and direct consume coefficient of i/o table, research and practical issues of enterprise information systemsⅡvolume 1, eds. l. xu, tjoa a. chaudhry s. (boston: springer),2008.3, pp. 145-152. (istp)。[24] ma, zs. et al (2012). a bird's eye view of microbial community dynamics. in “microbial ecological theory: current perspectives.” caister academic press, editor: eds. by lesley a. ogilvie and penny r. hirsch.。

5 van Dijk MC, Bernsen MR, Ruiter DJ. Analysis of Mutations in B-RAF, N-RAS, and H-RAS Genes in the Differential Diagnosis of Spitz Nevus and Spitzoid Melanoma. Am J Surgical Pathology,2005;29(9):1145-1151

6 Uribe P, Wistuba II, Gonzalez S. BRAF Mutation: A Frequent Event in Benign, Atypical, and Malignant Melanocytic Lesions of the Skin. Am J Dermatopathology,2003;25(5):365-370

7孟秀娟.端粒酶在肿瘤疾病中的表达及研究进展.河北医药,2003;25(4):305-306

8 Wu A, Ichihashi M, Ueda M. Correlation of the expression of human telomerase subunits with telomerase activity in nomal skin and skin tumors. Cancer ,1999; 86(10):2038-2044

2) zhao yy, xue c, hou x, liao h, li s, zhao hy, huang y, chen lk, xu f, liu jl, zhang l changes of bone resorption marker (ntx) in chemotherapy plus zoledronic acid versus chemotherapy alone for nasopharyngeal cancer patients with bone metastases. eur j cancer. 2011 apr。results of 20 patients with malignant diffuse pleural mesothelioma, pleural thickening more than 10 mm in 19 patients(95%), nodular/massive pleural thickening in 13(68%), rind-like pleural thickening in 15(75%), mediastinal pleural involvement in 18(90%), contraction of the involved hemithorax in all 20 patients.。5、hu shengping,wang mingliang,wu zhiyuan,zhao xuesong,miao fei#. gemestone spectral monochromatic ct imaging:detection and classification of focal liver lesions in patients with pancreatic cancer. euroasian hepato-gastroenterology,2011。

10 Miracco C, Pacenti L, Santopietro R, Laurini L, Biagioli M, Luzi P. Evaluation of telomerase activity in cutaneous melanocytic proliferations. Human Pathology,2000; 31(9):1018-1021

11 Villa R, Porta CD, Folini M. Possible regulation of telomerase activity by transcription and alternative splicing of telomerase reverse transcriptase in human melanoma. J Invest Dermatology ,2001;116(6):867-873

12范松青,魏启幼.原位杂交法检测恶性黑色素瘤中人类端粒酶RNA及人类端粒酶催化亚单位mRNA的表达.中华皮肤科杂志,2001;34(4):292

13李慎秋,熊芬,张春梅. hTERT在原发性皮肤恶性黑色素瘤中的表达.华中科技大学学报,2006;35(2):244-246

14 Rudolph P, Schubert C, Tamm S, Heidorn K, Hauschild A, Michalska I, Majewski S, Krupp G, Jablonska S, Parwaresch R. Telomerase activity in melanocytic lesions: A potential marker of tumor biology. Am J Pathology ,2000;156(4):1425-1432

15 Fullen DR, Zhu W, Thomas D, Su LD. hTERT expression in melanocytic lesions: an immunohistochemical study on paraffin-embedded tissue. Ournal Cutaneous Pathology,2005;32(10):680-684

16 陶娟,涂亚庭. 一氧化氮、一氧化氮合酶与恶性黑色素瘤.国外医学皮肤性病学分册,2004;30(1):44-47

m afraid so.she has a malignant growth.”i stood up.“there&rsquo。15(4):461-70[32]haider as,lowes ma,suarez-farinas m,et al.identification of cellular pathways of“type1”,th17 tcells, and tnf-and inducible nitric oxide synthase-producingdendritic cells in autoimmune inflammation through pharmacogenomic study ofcyclosporinea in psoriasis[j].j immunol,2008。09. ※liying gu1, lan dai1, cong cao1, jing zhu, chuanwei ding, hai-bo xu, lihua qiu, wen di. functional expression of tweak and the receptor fn14 in human malignant ovarian tumors: possible implication for ovarian tumor intervention. plos one.2013, 8(3):e57436.。

6. kong f, liu j, liu y, song b, wang h, liu w. association of interleukin-10 gene polymorphisms with breast cancer in a chinese population. journal of experimental & clinical cancer research. 2010 jun 17。12. song b, wang c, liu j, wang x, lv l, wei l, xie l, zheng y, song x. microrna-21 reg- ulates breast cancer invasion partly by targeting tissue inhibitor of metalloproteinase 3 xpression. journal of experimental & clinical cancer research. 2010 mar 27。【key words】 ethical review, clinical research, medical research management。