Written in English
Chondrosarcomas are malignant cartilage tumours that often arise from benign precursor lesions known as enchondromas. Some cases of multiple enchondromas are caused by a mutation in the parathyroid hormone related protein receptor (PTHR1), resulting in constitutive activation of Hedgehog (HH) mediated signalling. 120 chondrosarcoma xenografts from 12 different human malignancies were established in NOD-SCID mice. Treatment with triparanol, an inhibitor of HH signalling, resulted in a 60% decrease in tumour volume, a 30% decrease in cellularity, and a 20% reduction in proliferation rate. Thus, it is demonstrated that HH signalling is active and regulates tumour cell proliferation in chondrosarcomas. These results raise the intriguing possibility that the pharmacological blockade of HH signalling could be used as an effective treatment for chondrosarcomas, a malignancy for which there are currently no universally effective non-surgical management options.
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Title: Modulators of Hedgehog Signaling in Neoplasia; Author: Ho, Louisa Advisor: Alman, BenjaminAuthor: Louisa Ho. Hedgehog signalling influences development and homeostasis of many gut-derived organs, some of which give rise to Hh-dependent cancers. In the foregut, for example, ligand-dependent pathway activity is required for growth of a significant proportion of small-cell lung cancers and of carcinomas of the stomach, oesophagus. Hedgehog signalling regulates several cellular processes that are critical in bone development Osteoarthritis and cartilaginous neoplasia are associated with activation of the hedgehog signalling Cited by: During the development of growth plate cartilage, pre-hypertrophic and hypertrophic chondrocytes express Indian hedgehog signaling, while Glioma-associated oncogene-1, a downstream target of.
Dysregulation of Indian hedgehog - Parathyroid hormone related protein signatling ris a mechanism of cartilaginous neoplasia Degree of Doctor of Philosophy, Sevan Hopyan Institute of Medical Science University of Toronto ABSTRACT Enchondroma is a benign cartilage - forming tumour of bone that might be çausedAuthor: Sevan Hopyan. The gastrointestinal tract is the third most common site of neoplastic disease in the hedgehog, accounting for 16% of reported tumors.1, 4 In a retrospective necropsy review of 74 hedgehogs, neoplasia was found in approximately 7% of cases with gastrointestinal tract lesions. 2 The most common tumor of the gastrointestinal tract in the hedgehog is oral squamous cell carcinoma; Cited by: Benign cartilage lesions (enchondromas and osteochondromas) can result from the deregulation of the hedgehog signalling pathway, which is Cited by: D: Aberrant IHH-PTHrP signaling in cartilage neoplasia. The ability of PTHrP to inhibit IHH expression is lost leading to constitutive Hedgehog signaling. The ability of PTHrP to inhibit IHH expression is lost leading to constitutive Hedgehog by:
The Hedgehog (Hh) signaling pathway regulates embryonic development and may be aberrantly activated in a wide variety of human cancers. Efforts to target pathogenic Hh signaling have steadily progressed from the laboratory to the clinic, and the recent approval of the Hh pathway inhibitor vismodegib for patients with advanced basal cell carcinoma Cited by: from book Cartilage: Volume 1: Hedgehog signalling is mediated by the primary cilium and promotes cartilage degeneration in osteoarthritis. osteoarthritis or cartilaginous neoplasia. Primary cilia can act as either a negative or positive regulator of the hedgehog (Hh) signaling pathway. Many cartilage tumors are characterized by abnormal activation of the Hh pathway. Here, we report that the presence of primary cilia occurs at a low frequency (%) in neoplastic chondrocytes from malignant human chondrosarcomas, compared with chondrocytes from normal articular cartilage Cited by: In this study we investigated IHH-PTHrP signaling in cartilage tumors. Although previous studies examined PTHrP signals in cartilage neoplasia, the role of HH signals has received little attention. Here we show that HH signals are active in chondrosarcoma and benign cartilage tumors and that feedback inhibition of PTHrP on IHH expression is by: