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Vismodegib

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https://www.readbyqxmd.com/read/29164817/regulation-of-hedgehog-signaling-in-cancer-by-natural-and-dietary-compounds
#1
REVIEW
Cheng Bao, Pavel Kramata, Hong Jin Lee, Nanjoo Suh
The aberrant Hedgehog (Hh) signaling induced by mutations or overexpression of the signaling mediators has been implicated in cancer, associated with processes including inflammation, tumor cell growth, invasion and metastasis, as well as cancer stemness. Small molecules targeting the regulatory components of the Hh signaling pathway, especially Smoothened (Smo), have been developed for the treatment of cancer. However, acquired resistance to a Smo inhibitor vismodegib observed in clinical trials suggests that other Hh signaling components need to be explored as potential anticancer targets...
November 21, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29164054/effective-drug-delivery-in-diffuse-intrinsic-pontine-glioma-a-theoretical-model-to-identify-potential-candidates
#2
Fatma E El-Khouly, Dannis G van Vuurden, Thom Stroink, Esther Hulleman, Gertjan J L Kaspers, N Harry Hendrikse, Sophie E M Veldhuijzen van Zanten
Despite decades of clinical trials for diffuse intrinsic pontine glioma (DIPG), patient survival does not exceed 10% at two years post-diagnosis. Lack of benefit from systemic chemotherapy may be attributed to an intact bloodbrain barrier (BBB). We aim to develop a theoretical model including relevant physicochemical properties in order to review whether applied chemotherapeutics are suitable for passive diffusion through an intact BBB or whether local administration via convection-enhanced delivery (CED) may increase their therapeutic potential...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29132849/treatment-of-vismodegib-associated-muscle-cramps-with-cyclobenzaprine-a-retrospective-review
#3
Yul W Yang, James B Macdonald, Steven A Nelson, Aleksandar Sekulic
No abstract text is available yet for this article.
December 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29131041/skin-manifestations-of-targeted-antineoplastic-therapy
#4
Onofre Sanmartín
The management of oncology patients has changed significantly over recent years, with the development of new targeted anticancer therapies. Cutaneous adverse effects are among the most frequently observed toxicities with many targeted agents; their intensity can be dose-limiting or lead to the discontinuation of therapy. Tyrosine kinase inhibitors can cause maculopapular rash and hand-foot reaction, whereas papulopustular rash, paronychia, regulatory changes in hair, and dryness are caused by epidermal growth factor receptor inhibitors...
2018: Current Problems in Dermatology
https://www.readbyqxmd.com/read/29111235/genomic-stability-in-syndromic-basal-cell-carcinoma
#5
Audris Chiang, Prajakta D Jaju, Prag Batra, Melika Rezaee, Ervin H Epstein, Jean Y Tang, Kavita Y Sarin
Basal cell cancers (BCCs) are characterized by up-regulation of Hedgehog pathway through loss of Patched1 or activation of Smoothened, and smoothened-inhibitors such as vismodegib are effective therapies for advanced BCCs. Although most BCCs are sporadic, rare individuals with Basal Cell Nevus Syndrome (BCNS) harbor germline defects in Patched1 and develop up to hundreds of tumors that are histopathologically indistinguishable from sporadic BCCs. Interestingly, BCNS-BCCs are more responsive to Smoothened-inhibitors than sporadic BCCs, with minimal development of resistance...
October 27, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29107429/discovery-of-1-3-aryl-4-chlorophenyl-3-p-aryl-urea-derivatives-against-breast-cancer-by-inhibiting-pi3k-akt-mtor-and-hedgehog-signalings
#6
Wenlu Li, Qinsheng Sun, Lu Song, Chunmei Gao, Feng Liu, Yuzong Chen, Yuyang Jiang
PI3K/Akt/mTOR and hedgehog (Hh) signalings are two important pathways in breast cancer, which are usually connected with the drug resistance and cancer migration. Many studies indicated that PI3K/Akt/mTOR inhibitors and Hh inhibitors displayed synergistic effects, and the combination of the two signaling drugs could delay drug resistance and inhibit cancer migration in breast cancer. Therefore, the development of molecules simultaneously inhibiting these two pathways is urgent needed. Based on the structures of PI3K inhibitor buparlisib and Hh inhibitor vismodegib, a series of hybrid structures were designed and synthesized utilizing rational drug design and computer-based drug design...
December 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29102653/combination-vismodegib-and-photodynamic-therapy-for-multiple-basal-cell-carcinomas
#7
Jason M Rizzo, Robert J Segal, Nathalie C Zeitouni
BACKGROUND: Oral vismodegib therapy and photodynamic therapy (PDT) are non-invasive treatments for basal cell carcinoma (BCC) with overlapping utility in widespread BCCs and patients who are poor surgical candidates. There is no published study to date investigating the combination use of PDT with vismodegib to optimize individual response rates. OBJECTIVE: To evaluate the combination of red light PDT and vismodegib therapy in patients with multiple nodular BCCs...
November 1, 2017: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/29078327/hedgehog-signaling-regulates-ciliary-localization-of-mouse-odorant-receptors
#8
Devendra Kumar Maurya, Staffan Bohm, Mattias Alenius
The ciliary localization of odorant receptors (ORs) is evolutionary conserved and essential for olfactory transduction. However, how the transport of ORs is regulated in mammalian olfactory sensory neurons is poorly understood. Here we demonstrate that odorant responsiveness and OR transport is regulated by the Hedgehog pathway. OR transport is inhibited by conditional gene inactivation of the Hedgehog signal mediator Smoothened (Smo) as well as by systemic administration of the Smo inhibitor vismodegib, a clinically used anticancer drug reported to distort smell perception in patients...
October 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29073584/vismodegib-in-patients-with-advanced-basal-cell-carcinoma-primary-analysis-of-stevie-an-international-open-label-trial
#9
N Basset-Séguin, A Hauschild, R Kunstfeld, J Grob, B Dréno, L Mortier, P A Ascierto, L Licitra, C Dutriaux, L Thomas, N Meyer, B Guillot, R Dummer, P Arenberger, K Fife, A Raimundo, E Dika, N Dimier, A Fittipaldo, I Xynos, J Hansson
BACKGROUND: The SafeTy Events in VIsmodEgib study (STEVIE, ClinicalTrials.gov, NCT01367665), assessed safety and efficacy of vismodegib-a first-in-class Hedgehog pathway inhibitor demonstrating clinical benefit in advanced basal cell carcinoma (BCC)-in a patient population representative of clinical practice. Primary analysis data are presented. PATIENTS AND METHODS: Patients with locally advanced or metastatic BCC received oral vismodegib 150 mg/d until progressive disease, unacceptable toxicity, or withdrawal...
November 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29057423/9q22-3-microdeletion-syndrome-with-multiple-basal-cell-carcinomas-treated-with-vismodegib-three-key-messages-in-one-patient
#10
Alice Kieny, Valérie Kremer, Sophie Scheidecker, Dan Lipsker
No abstract text is available yet for this article.
October 23, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/29055164/reflectance-confocal-microscopy-identification-of-subclinical-basal-cell-carcinomas-during-and-after-vismodegib-treatment
#11
Caroline Couzan, Elisa Cinotti, Bruno Labeille, Paul Vercherin, Pietro Rubegni, Frédéric Cambazard, Jean Luc Perrot
BACKGROUND: Recently, it has been shown that reflectance confocal microscopy (RCM) could identify subclinical basal cell carcinoma (BCC) during vismodegib treatment of locally-advanced BCC. OBJECTIVES: To evaluate specificity and sensitivity of clinical, dermoscopic and RCM examination for BCC in patients with multiple BCCs treated by vismodegib. METHODS: 94 BCCs had 710 clinical, dermoscopic and RCM examinations during 72 weeks of vismodegib treatment...
October 21, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29050204/irreversible-growth-plate-fusions-in-children-with-medulloblastoma-treated-with-a-targeted-hedgehog-pathway-inhibitor
#12
Giles W Robinson, Sue C Kaste, Wassim Chemaitilly, Daniel C Bowers, Stephen Laughton, Amy Smith, Nicholas G Gottardo, Sonia Partap, Anne Bendel, Karen D Wright, Brent A Orr, William C Warner, Arzu Onar-Thomas, Amar Gajjar
The permanent defects in bone growth observed in preclinical studies of hedgehog (Hh) pathway inhibitors were not substantiated in early phase clinical studies of vismodegib in children. Consequently, vismodegib advanced into pediatric trials for malignancies suspected of being driven by aberrant activation of the Hh pathway. In one multicenter phase II trial, vismodegib was added to the therapy regimen for newly diagnosed Hh pathway activated medulloblastoma. Herein, we report on 3 children (2 on trial and one off trial) treated with vismodegib who developed widespread growth plate fusions that persist long after cessation of therapy...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29030893/sonic-hedgehog-antagonists-reduce-size-and-alter-patterning-of-the-frog-inner-ear
#13
Sanam Zarei, Kasra Zarei, Bernd Fritzsch, Karen L Elliott
Sonic hedgehog (Shh) signaling plays a major role in vertebrate development, from regulation of proliferation to the patterning of various organs. In amniotes, Shh affects dorsoventral patterning in the inner ear but affects anteroposterior patterning in teleost ears. It remains unknown how altered function of Shh relates to morphogenetic changes that coincide with the evolution of limbs and novel auditory organs in the ear. In this study, we used the tetrapod, Xenopus laevis, to test how increasing concentrations of the Shh signal pathway antagonist, Vismodegib, affects ear development...
December 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/28976624/vismodegib-persistence-and-discontinuation-patterns-in-greek-patients-from-a-real-world-setting
#14
Efthymia Soura, Michaela Plaka, Vasiliki Chasapi, Christina Antoniou, Alexander Stratigos
Hedghehog pathway inhibitors have been successfully used for patients with locally advanced basal cell carcinomas. However, these treatments have been associated with various adverse events that may limit patient compliance. In this study, an association of patient and disease characteristics with drug compliance in a real clinical setting was made. 18 patients were included in the study. The average patient age was 78.39 years. The time that patients remained to treatment was, on average, 8.73 months. 72.2% of patients experienced at least one adverse event...
October 4, 2017: Dermatologic Therapy
https://www.readbyqxmd.com/read/28932790/medical-marijuana-for-the-treatment-of-vismodegib-related-muscle-spasm
#15
Joyce T Yuan, Tiffany L Tello, Carter Hultman, Christopher A Barker, Sarah T Arron, Sue S Yom
No abstract text is available yet for this article.
September 2017: JAAD Case Reports
https://www.readbyqxmd.com/read/28887802/small-molecule-inhibitors-of-the-hedgehog-pathway-in-the-treatment-of-basal-cell-carcinoma-of-the-skin
#16
REVIEW
Rebecca Danhof, Karl Lewis, Mariah Brown
Basal cell carcinoma (BCC) is the most common type of skin cancer, with rising incidence rates primarily attributed to an aging population and ultraviolet radiation exposure. While the majority of BCCs are localized and respond to standard therapies, a very small minority of these tumors become locally destructive or metastasize. These advanced BCCs may not be amenable to localized treatment with surgery and/or radiation therapy. Most BCCs result from mutations in key receptors in the Hedgehog (HH) signaling pathway...
September 8, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28881358/ligand-dependent-hedgehog-pathway-activation-in-rhabdomyosarcoma-the-oncogenic-role-of-the-ligands
#17
A Almazán-Moga, P Zarzosa, C Molist, P Velasco, J Pyczek, K Simon-Keller, I Giralt, I Vidal, N Navarro, M F Segura, A Soriano, S Navarro, O M Tirado, J C Ferreres, A Santamaria, R Rota, H Hahn, J Sánchez de Toledo, J Roma, S Gallego
BACKGROUND: Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children. The Hedgehog (HH) pathway is known to develop an oncogenic role in RMS. However, the molecular mechanism that drives activation of the pathway in RMS is not well understood. METHODS: The expression of HH ligands was studied by qPCR, western blot and immunohistochemistry. Functional and animal model studies were carried out with cells transduced with shRNAs against HH ligands or treated with HH-specific inhibitors (Vismodegib and MEDI-5304)...
October 24, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28865507/-gorlin-goltz-syndrome-diagnosis-and-treatment-options
#18
João Mendes-Abreu, Miguel Pinto-Gouveia, Cátia Tavares-Ferreira, Ana Brinca, Ricardo Vieira
The Gorlin-Goltz syndrome is a rare autosomal dominant hereditary condition, with complete penetrance and variable expressivity. Characterized by the appearance of multiple basaliomas, and often the development of keratocyst, it can also express itself by the presence of palmar/plantar depressions, calcification of brain sickle, and skeletal birth defects, although less frequently. This article presents two cases involving direct relatives, referred after the identification of several basaliomas and jaw cysts...
May 31, 2017: Acta Médica Portuguesa
https://www.readbyqxmd.com/read/28863112/disruption-of-hedgehog-signaling-by-vismodegib-leads-to-cleft-palate-and-delayed-osteogenesis-in-experimental-design
#19
Shixian Zhang, Chengyong Wang, Changfu Xie, Yongzhen Lai, Di Wu, Guowu Gan, Weihui Chen
The function of hedgehog signaling has previously been shown to be crucial for craniofacial development. In this study, we treated C57/BL6J mice with the hedgehog pathway inhibitor vismodegib by oral gavage to establish a stable vismodegib-induced cleft palate model. At E10.5 and E12.5, mice in the experimental group were treated with 100 mg/kg of vismodegib, whereas mice in the control group were treated with solvent. The treated pregnant mice were sacrificed on E13.5, E14.5, E15.5, and E16.5. Palatal shelf growth was evaluated via histological and immunohistochemical analyses as well as palatal organ culture...
September 2017: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/28831360/vismodegib-for-locally-advanced-periocular-and-orbital-basal-cell-carcinoma-a-review-of-15-consecutive-cases
#20
Kai Yuen Wong, Kate Fife, John T Lear, Richard D Price, Amer J Durrani
Basal cell carcinoma (BCC) is the most common periocular skin cancer and can lead to significant morbidity. We assess the effectiveness of vismodegib, a first-in-class Hedgehog signaling pathway inhibitor, in the management of periocular and orbital BCCs based on clinical response, tolerability, and orbital content preservation. All patients with periocular or orbital BCCs who met criteria for vismodegib treatment were recruited prospectively between May 2012 and 2014 from 2 hospitals. Patients received oral vismodegib (150 mg daily) until disease progression, unacceptable toxicity, or withdrawal...
July 2017: Plastic and Reconstructive Surgery. Global Open
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