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61.
Linda Holmquist Mengelbier Simon Lindell-Munther Hiroaki Yasui Caroline Jansson Javanshir Esfandyari Jenny Karlsson Kimberly Lau Chi-chung Hui Daniel Bexell Sevan Hopyan David Gisselsson 《The Journal of pathology》2019,247(1):86-98
Wilms tumour is a paediatric malignancy with features of halted kidney development. Here, we demonstrate that the Iroquois homeobox genes IRX3 and IRX5 are essential for mammalian nephrogenesis and govern the differentiation of Wilms tumour. Knock-out Irx3−/Irx5− mice showed a strongly reduced embryonic nephron formation. In human foetal kidney and Wilms tumour, IRX5 expression was already activated in early proliferative blastema, whereas IRX3 protein levels peaked at tubular differentiation. Accordingly, an orthotopic xenograft mouse model of Wilms tumour showed that IRX3−/− cells formed bulky renal tumours dominated by immature mesenchyme and active canonical WNT/β-catenin-signalling. In contrast, IRX5−/− cells displayed activation of Hippo and non-canonical WNT-signalling and generated small tumours with abundant tubulogenesis. Our findings suggest that promotion of IRX3 signalling or inhibition of IRX5 signalling could be a route towards differentiation therapy for Wilms tumour, in which WNT5A is a candidate molecule for enforced tubular maturation. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. 相似文献
62.
Yuzhakov V. V. Malinova I. V. Kiseleva M. V. Fomina N. K. Bandurko L. N. Komarova E. V. Sevan’kaeva L. E. Ingel’ I. E. Yakovleva N. D. Kaprin A. D. 《Bulletin of experimental biology and medicine》2018,164(4):502-507
Bulletin of Experimental Biology and Medicine - The results of a complex morphofunctional study with markers of proliferation (PCNA and Ki-67), angiogenesis (CD31 and CD34), and structural... 相似文献
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Sevan Hopyan 《Journal of children's orthopaedics》2021,15(4):358
Reconstructions for paediatric bone tumours of the shoulder girdle and humerus are intended to optimize placement of the hand in space. Given the longevity of paediatric survivors of sarcoma, durability is an important planning consideration. Here, I review a subset of approaches based on anatomical site with an emphasis on function and longevity. Often, biological reconstructions that combine living bone with tendon repairs and transfers best address those goals. 相似文献
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High temperature superconducting (SC) nanocomposites based on SC ceramics and various polymeric binders were prepared. Regardless of the size of the ceramics’ grains, the increase of their amount leads to an increase of resistance to rupture and modulus and a decrease in limiting deformation, whereas an increase in the average ceramic grain size worsens resistance properties. The SC, thermo-chemical, mechanical and dynamic-mechanical properties of the samples were investigated. Superconducting properties of the polymer ceramic nanocomposites are explained by intercalation of macromolecule fragments into the interstitial layer of the ceramics’ grains. This phenomenon leads to a change in the morphological structure of the superconducting nanocomposites. 相似文献
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68.
Constitutive hedgehog signaling in chondrosarcoma up-regulates tumor cell proliferation 总被引:3,自引:0,他引:3 下载免费PDF全文
Tiet TD Hopyan S Nadesan P Gokgoz N Poon R Lin AC Yan T Andrulis IL Alman BA Wunder JS 《The American journal of pathology》2006,168(1):321-330
Chondrosarcoma is a malignant cartilage tumor that may arise from benign precursor lesions, such as enchondromas. Some cases of multiple enchondromas are caused by a mutation that results in constitutive activation of Hedgehog-mediated signaling. We found that chondrosarcomas expressed high levels of the Hedgehog target genes PTCH1 and GLI1. Treatment with parathyroid hormone-related protein down-regulated Indian Hedgehog (IHH) expression in normal growth plates but not in chondrosarcoma or enchondroma organ cultures. Treatment of the chondrosarcoma organ cultures with Hedgehog protein increased cell proliferation rate, whereas addition of chemical inhibitors of Hedgehog signaling decreased the proliferation rate. Chondrosarcoma xenografts from 12 different human tumors were established in NOD-SCID mice. Treatment with triparanol, an inhibitor of Hedgehog signaling, resulted in a 60% decrease in tumor volume, a 30% decrease in cellularity, and a 20% reduction in proliferation rate. These results show that Hedgehog signaling is active in chondrosarcoma and benign cartilage tumors and regulates tumor cell proliferation. Our data raise the intriguing possibility that Hedgehog blockade could serve as an effective treatment for chondrosarcoma, a tumor for which there are currently no universally effective nonsurgical management options. 相似文献
69.
Göksan SB Bursali A Bilgili F Sivacioğlu S Ayanoğlu S 《Archives of orthopaedic and trauma surgery》2006,126(1):15-21
Introduction: The aim of this study is to evaluate the effectiveness of the Ponseti method in children presenting before 1 year of age
with either untreated or complex (initially treated unsuccessfully by other conservative methods) idiopathic clubfeet. Patients and methods: The authors report 134 feet of 92 patients with Dimeglio grade 2, 3, or 4 deformities treated with the Ponseti method. Twenty-four
percent of feet were of complex deformities at initial presentation to the authors’ clinics. Results: At a mean follow-up of 46 months (range 24–89) we avoided joint release surgery in 97% of feet. Sixty-seven percent required
a percutaneous tenotomy of the Achilles tendon. Relapse rate was 31% (41 feet). We treated 2 relapses by restarting the use
of orthosis, 17 with re-casting, 18 with anterior tibial tendon transfer following a second relapse, and 4 feet with extensive
joint surgery. Compliance with the use of orthosis was identified as the most important risk factor (P<0.0001) for relapses. Previous unsuccessful treatment attempts by other conservative methods did not adversely affect the
results unless the cases had iatrogenic deformities. Cases with iatrogenic deformities from previous treatment had a significantly
increased risk of non-compliance and relapse. Experience of the treating surgeon and cast complications were also related
to relapses. Conclusion: Our results show that the Ponseti technique is reproducible and effective in children at least up to 12 months of age. It
can also produce good correction in children presenting with complex idiopathic deformities. Therefore, extensive joint releases
should not be considered immediately in such cases. The treating surgeon should be meticulous in using the technique and ensure
compliance to foot abduction brace in order to avoid recurrences. 相似文献
70.
Sevan C. Grant 《Australasian journal on ageing》2003,22(3):136-140
Although one's home may be endowed with memories and meanings increasing numbers of people 65 years and over are changing their place of residence and/or community in search of an alternative lifestyle. One type of community attracting considerable interest is a retirement village. Over the past decade New Zealand has witnessed a rapid increase in the number of such communities designed to provide an idyllic and hassle‐free lifestyle in a clean well maintained and secure environment. But in spite of ‘relatively trouble free existence’ that is supposedly associated with these purpose built environments there are a number of social, economic and political issues that warrant further comment. After all, retirement villages are more than just a place to live. 相似文献