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91.
92.
Treatment of Eyelid Epithelial Neoplasm by Targeting Sonic Hedgehog Signaling: An Experimental Study
Miyazaki K Saika S Yamanaka O Okada Y Ohnishi Y 《Japanese journal of ophthalmology》2006,50(4):305-311
Purpose
To evaluate the effect of cyclopamine, an inhibitor of the Sonic hedgehog (Shh) signal, on the growth of an epithelial neoplasm.Methods
Chemically induced eyelid tumors in XPC-null mice (n = 40) were treated daily with a subcutaneous injection of cyclopamine (1?mg/animal) for 7 days. The animals were killed after bromodeoxyuridine (BrdU) labeling, and the tumors were histologically examined. An in vitro study was conducted by using a squamous cell carcinoma (SCC) cell line. The SCC cells were treated with 0, 12.5, or 25.0?μg/ml recombinant Shh (rShh) and either 0 or 100?μM cyclopamine, and cell proliferation was evaluated by using an MTT assay. Cells from this cell line were also implanted subcutaneously in nude mice (n = 8) to develop tumors, and the effect of cyclopamine administration was examined in the developed tumors.Results
Histology showed that cyclopamine treatment suppressed BrdU incorporation and induced apoptosis in the majority of cells in tumors chemically induced in the eyelid of the XPC-null mice. Cell proliferation of the SCC cell line was enhanced by adding rShh, and this effect was abolished by adding cyclopamine. Proliferation of the SCC cell line was not affected by adding cyclopamine in the absence of rShh. On the other hand, the SCC cells expressed Shh in vivo in tumors developed in nude mice, but cyclopamine suppressed cell proliferation in the tumors, and the Shh-signaling pathway was inhibited by cyclopamine-induced apoptosis.Conclusions
Cyclopamine inhibits proliferation and induces apoptosis in epithelial tumor cells in vivo. The Shh-signaling pathway may be a potential therapeutic target for patients with eyelid tumors.?Jpn J Ophthalmol 2006;50:305–311 © Japanese Ophthalmological Society 2006 相似文献93.
J. H. Hersh T. V. Dela Cruz M. Pietrantoni G. von Drasek-Ascher M. A. Turnquest O. A. Yacoub M. R. Joyce 《American journal of medical genetics. Part A》1995,59(3):341-345
Mirror image duplication of the hands and feet is a rare entity. Based on 3 previous reports, findings include nasal abnormalities, dimelia of ulna and fibula, tibial hypoplasia and mirror image duplication of hands and feet. We report on a sporadic case in which mirror image duplication was associated with multiple congenital anomalies. Although these cases may represent variable expression of the same dominantly transmitted complex polysyndactyly syndrome, it is possible that mirror image duplication of the hands and feet is a manifestation common to a number of distinct clinical entities. During limb bud development, duplication and aberrant positioning of the zone of polarizing activity in relation to the apical ectodermal ridge may account for the anatomic abnormalities of the hands and feet in these patients. © 1995 Wiley-Liss, Inc. 相似文献
94.
The hippocampal mossy fiber zone of the European hedgehog has been studied at the light and electron microscopic levels. In contrast to the organization of this zone in other mammals, the mossy fiber zone of the hedgehog is not confined to the region of Ammon's horn that is characterized by large pyramidal cells (i.e. regio inferior) but extends into the region that contains small pyramidal cells (i.e. regio superior). The terminal, throughout the relatively extensive mossy fiber zone of the hedgehog, have the large multivesicular, multicontact morphology that characterizes the mossy fiber terminals observed in other species and can be demonstrated to be the axon terminals of granule cells located in the fascia dentata. In view of the primitive organization of the forebrain of the European hedgehog, which is believed to be representative of that of the first mammals, the boundaries of the mossy fiber zone of these animals suggest that the mossy fibers extended over a larger part of Ammon's horn during the first phases of mammalian evolution and became restricted to the regio inferior during the early stages of mammalian evolution. 相似文献
95.
Scott WJ Schreiner CM Goetz JA Robbins D Bell SM 《Reproductive toxicology (Elmsford, N.Y.)》2005,19(4):479-485
Administration of CdSO4 to C57BL/6 mice at day 9.5 of gestation induces a high incidence of postaxial forelimb ectrodactyly in the offspring. We propose that Cd2+ exposure impairs the process of anterior/posterior formation in the limb bud, a process that is directed by Sonic hedgehog (Shh) signaling. We show that exposure of the mouse embryo to Cd2+ disrupts Shh signaling as measured by polarizing activity of mouse limb bud ZPA grafted to a host chick wing, and activity of a Gli:luciferase reporter exposed to limb bud lysates. Yet the expression of Shh and its translation are not affected by Cd2+ exposure. We propose that teratogen exposure affects the processing of Shh in the cells in which it is made. 相似文献
96.
The occurrence of four gastrointestinal (GIT) anomalies in a single patient is extremely rare. Only one report of four GIT anomalies in a child has been published in the English literature. The current report presents a child with four anomalies and discusses the molecular mechanisms which control the development of the gastrointestinal tract. 相似文献
97.
The present case report describes two patients with a novel combination of VACTERL (vertebral, anorectal, cardiac, tracheoesophageal, renal, limb), neural tube defect and crossed renal ectopia. Though cases of VACTERL associated with crossed renal ectopia have been described, the present case report is the first to describe its combination with neural tube defect. The cases reported here are significant because central nervous system manifestations are scarce in VACTERL syndrome. The role of sonic hedgehog pathway has been proposed in VACTERL association and neural tube defects. Axial Sonic hedgehog signaling has also been implicated in the mediolateral positioning of the renal parenchyma. With this knowledge, the etiopathogenesis of this novel combination is discussed to highlight the role of sonic hedgehog signaling as a point of coherence. 相似文献
98.
Sonic Hedgehog(SHH)信号通路不仅在胚胎期发育起重要作用,而且在生后保持组织或器官的完整和功能发育中起重要作用.近年来在肺部疾病中发现SHH信号通路异常激活,提示SHH信号通路可能在肺部疾病中起一定作用. 相似文献
99.
100.
目的 探讨神经发育音猬因子(SHH)诱导恒河猴骨髓间质细胞(BMSCs)向神经样细胞分化的丝裂原活化蛋白激酶信号分子变化. 方法 密度梯度离心法分离培养恒河猴骨髓干细胞,应用Westem-blot方法检测SHH诱导细胞内信号蛋白变化,免疫组化方法观察丝裂原活化蛋白激酶(MAPK)特异性抑制剂对细胞诱导过程的影响. 结果 SHH诱导恒河猴BMSCs分化为神经样细胞分化过程,细胞内激酶p38在加入诱导液5 min后即被激活,随着时间的延长持续升高,1h达到最高峰,诱导前、后p38的总量未见变化;而磷酸化的ERKl/2被抑制,5 min时即开始减少,在2h内逐渐降低,诱导前、后ERKl/2的总量未见变化. 结论 MAPK激酶系统参与SHH诱导恒河猴MSCs分化为神经样细胞分化过程,p38被激活,而ERK被抑制. 相似文献