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Vismodegib

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https://www.readbyqxmd.com/read/29760872/giant-morphea-form-basal-cell-carcinoma-of-the-umbilicus-successful-debulking-with-vismodegib
#1
Mariana Orduz Robledo, Eve Lebas, Marie-Annick Reginster, Mahmoud Baghaie, Sabine Groves, Arjen F Nikkels
Basal cell carcinoma of the umbilicus is very rare. The nodular subtype is the main representative. Giant basal cell carcinomas represent around 1% of all basal cell carcinomas. The hedgehog pathway inhibitor vismodegib is indicated for advanced basal cell carcinoma and CD56-negative immunostaining seems indicative for successful treatment. A 54-year-old man presented a 10 cm × 14 cm large and 4.5 cm deep morphea-form basal cell carcinoma with faint immunohistochemical CD56 expression arising from the umbilicus...
2018: Rare Tumors
https://www.readbyqxmd.com/read/29742180/vismodegib-and-the-hedgehog-pathway-inhibitors-a-historical-perspective-to-current-clinical-application
#2
Jennifer C Tang, C William Hanke, Ivor Caro
Vismodegib (Erivedge, Genentech-Roche) is the first in class of Hedgehog pathway inhibitors approved for treatment of metastatic basal cell carcinoma (BCC), or locally advanced BCC that has recurred after surgery or is not amenable to surgery or radiation. Its path to discovery has been unique and traces its origin to corn lilies, sheep, Drosophila flies, and the Hedgehog signaling pathway. J Drugs Dermatol. 2018;17(5):506-508.
May 1, 2018: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/29682362/upfront-radiotherapy-with-concurrent-and-adjuvant-vismodegib-is-effective-and-well-tolerated-in-a-patient-with-advanced-multifocal-basal-cell-carcinoma
#3
Abigail I Franco, Gary Eastwick, Ramsay Farah, Marvin Heyboer, Mijung Lee, Paul Aridgides
We present a case report of a male with multifocal and extensive basal cell carcinoma. Due to extremely large size and deep tumor infiltration, he was not a surgical candidate. Combined modality treatment of fractionated radiation with concurrent vismodegib was chosen. Concurrent treatment was previously reported in the palliative and recurrent setting. This is the first case of concurrent vismodegib and radiation therapy for upfront definitive management. The patient experienced complete response in all treated lesions...
2018: Case Reports in Dermatological Medicine
https://www.readbyqxmd.com/read/29682173/improved-therapy-for-medulloblastoma-targeting-hedgehog-and-pi3k-mtor-signaling-pathways-in-combination-with-chemotherapy
#4
Nagendra K Chaturvedi, Matthew J Kling, Don W Coulter, Timothy R McGuire, Sutapa Ray, Varun Kesherwani, Shantaram S Joshi, J Graham Sharp
Aberrant activation and interactions of hedgehog (HH) and PI3K/AKT/mTOR signaling pathways are frequently associated with high-risk medulloblastoma (MB). Thus, combined targeting of the HH and PI3K/AKT/mTOR pathways could be a viable therapeutic strategy to treat high-risk patients. Therefore, we investigated the anti-MB efficacies of combined HH inhibitor Vismodegib and PI3K-mTOR dual-inhibitor BEZ235 together or combined individually with cisplatin against high-risk MB. Using non-MYC- and MYC-amplified cell lines, and a xenograft mouse model, the in vitro and in vivo efficacies of these therapies on cell growth/survival and associated molecular mechanism(s) were investigated...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29630158/a-case-illustrating-successful-eradication-of-recurrent-aggressive-basal-cell-carcinoma-located-in-a-scar-with-vismodegib
#5
Olivia M Lucero, Sarah Fitzmaurice, Curtis Thompson, Justin Leitenberge
Vismodegib is a small molecule inhibitor of the Hedgehog signaling pathway that has shown efficacy in the control of locally advanced or metastatic basal cell carcinoma, although proof of its effectiveness in the elimination of aggressive tumors is lacking. We report a case and provide complete histological evidence of a 69-year-old gentleman who presented with a recurrent, infiltrative, and sclerosing (morpheiform) basal cell carcinoma on his left upper lip that was entirely eradicated with a three-month course of vismodegib 150 mg daily...
February 15, 2018: Dermatology Online Journal
https://www.readbyqxmd.com/read/29626183/primary-basosquamous-carcinoma-of-the-lower-eyelid-with-ocular-invasion-a-case-report
#6
Georgios Ouilson Papadopoulos, Eleni Charitonidi, Nikolaos Filippou, Domna Fanidou, Dimitrios Filippou, Panagiotis Scandalakis
INTRODUCTION: Ocular invasion is extremely rare for a primary eyelid Basosquamous Carcinoma (BSC). It can however occur in neglected cases if the clinical signs are overseen and the BSC is misdiagnosed for a less aggressive skin carcinoma. MATERIALS AND METHODS: A 58-year-old man suffering from an inferior eyelid BSC that had been neglected for 7 years was referred to our clinic. A local infiltration of the maxillary sinus and the contents of the orbit by the tumor was discovered, and he was managed with a left orbital exenteration and resection of the involved orbital bone...
March 26, 2018: Annali Italiani di Chirurgia
https://www.readbyqxmd.com/read/29603722/effective-anti-pd-1-therapy-in-a-sufu-mutated-patient-with-gorlin-goltz-syndrome
#7
A Moreira, M C Kirchberger, F Toussaint, M Erdmann, G Schuler, L Heinzerling
We present a case of a 77-year-old male patient with more than 50 basal cell carcinomas on the head and upper trunk. The patient did not respond to several lines of treatment, including surgery, imiquimod, retinoids, itraconazole and therapy with the hedgehog inhibitor vismodegib. The patient responded well to an off-label therapy with the anti-PD-1 antibody pembrolizumab after 4 infusions. This article is protected by copyright. All rights reserved.
March 30, 2018: British Journal of Dermatology
https://www.readbyqxmd.com/read/29550418/sox9-transcriptionally-regulates-mtor-induced-proliferation-of-basal-cell-carcinomas
#8
Arianna L Kim, Jung Ho Back, Sandeep C Chaudhary, Yucui Zhu, Mohammad Athar, David R Bickers
Currently available SMO targeted therapies in patients with basal cell nevus syndrome (BCNS) are associated with substantial tumor recurrence and clinical resistance. Strategies bypassing SMO and/or identifying additional downstream components of the Hedgehog (Hh) pathway could provide novel anti-tumor targets with a better therapeutic index. SOX9 is a Hh/GLI-regulated transcription factor known to be overexpressed in BCCs. A sequence motif search for SOX9-responsive elements identified three motifs in the promoter region of mTOR...
March 14, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29515801/recurrent-extraneural-sonic-hedgehog-medulloblastoma-exhibiting-sustained-response-to-vismodegib-and-temozolomide-monotherapies-and-inter-metastatic-molecular-heterogeneity-at-progression
#9
Gregorio J Petrirena, Julien Masliah-Planchon, Quentin Sala, Bertrand Pourroy, Didier Frappaz, Emeline Tabouret, Thomas Graillon, Jean-Claude Gentet, Olivier Delattre, Olivier Chinot, Laetitia Padovani
Background: Response to targeting and non-targeting agents is variable and molecular information remains poorly described in patients with recurrent sonic-hedgehog-driven medulloblastoma (SHH-MB). Materials and Methods: Clinical and PET/CT findings during treatment with successive hedgehog antagonists and temozolomide monotherapies are described in a heavily pre-treated patient with recurrent extraneural metastases from PTCH1 mutated/ wild type smoothened ( SMO ) CNS SHH-MB...
February 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29484400/gli-family-zinc-finger-1-is-associated-with-endothelin-receptor-type-b-in-hirschsprung-disease
#10
Weizhen Liu, Juan Pan, Jinbo Gao, Xiaoming Shuai, Shaotao Tang, Guobin Wang, Kaixiong Tao, Chuanqing Wu
Hirschsprung disease (HSCR) is a newborn colorectal disease characterized by an absence of ganglia in the distal gut. Hedgehog (Hh) and endothelin signaling serve important roles in gastrointestinal tract formation. Alterations in the signaling pathways disrupt the development of enteric neural crest cells (ENCCs). It is not known whether there is any coordination between these pathways in the pathogenesis of HSCR. In the present study, tissue samples from 35 patients with HSCR, including stenotic aganglionosis gut and normal ganglionic gut, were obtained...
April 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29484007/locally-advanced-basal-cell-carcinoma-with-intraocular-invasion
#11
Georgi Tchernev, Torello Lotti, Ilia Lozev, Georgi Konstantinov Maximov, Uwe Wollina
We present a 103 - year - old patient, with duration of complaints of about ten years. The initial complaint had been presented as a small nodule, located on the eyebrow, which subsequently ulcerated and encompassed larger regions of the upper and lower eyelids. For the past three years, the patient also had complaints of a worsening of his vision, without seeking for medical help. Within the dermatological examination, an intraocular and periocular localised tumour was established, characterised by a raised peripheral edge and central ulceration...
January 25, 2018: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/29474275/development-and-validation-of-a-simultaneous-quantification-method-of-ruxolitinib-vismodegib-olaparib-and-pazopanib-in-human-plasma-using-liquid-chromatography-coupled-with-tandem-mass-spectrometry
#12
Claire Pressiat, Huu-Hien Huynh, Alain Plé, Hélène Sauvageon, Isabelle Madelaine, Cécile Chougnet, Christine Le Maignan, Samia Mourah, Lauriane Goldwirt
BACKGROUND: A simple, rapid, and sensitive liquid chromatography coupled with tandem mass spectrometry method has been developed and validated for the quantification of ruxolitinib, olaparib, vismodegib, and pazopanib in human plasma. METHODS: After a simple protein precipitation of plasma samples, the chromatographic separation was performed using an ultraperformance liquid chromatography system coupled with mass tandem spectrometry in a positive ionization mode...
June 2018: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/29462221/vismodegib-use-in-clinical-practice-analysis-of-a-united-states-medical-claims-database
#13
C William Hanke, Shivani K Mhatre, David Oliveri, Marko Zivkovic, Ivor Caro, Daniel Bergström, Keith Dawson, Camelia S Sima
BACKGROUND: Information is limited on the use of vismodegib for treatment of advanced basal cell carcinoma beyond the setting of clinical trials. OBJECTIVE: To investigate the treatment patterns and characteristics of patients treated with vismodegib in clinical practice. METHODS: A longitudinal, retrospective cohort study was undertaken using data from a US commercial insurance claims (Truven Health Analytics MarketScan) database. Eligible patients were ≥18 years of age, with ≥1 claim for vismodegib from January 2012 to December 2015...
February 1, 2018: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/29454489/basal-cell-nevus-syndrome-gorlin-syndrome-genetic-insights-diagnostic-challenges-and-unmet-milestones
#14
Maryam Akbari, Harold Chen, Grace Guo, Zachary Legan, Ghali Ghali
In this article, we present three clinical case reports on Basal Cell Nevus Syndrome (Gorlin Syndrome). Gorlin syndrome is an inherited medical condition with challenges that manifest in multiple body systems and complicate early diagnosis. We examine the epidemiology of the disease and benefits of genetic testing, molecular pathophysiology, and advancement in the molecular-based therapy of Basal Cell Nevus syndrome. The goal of this paper is to shed light on both unmet challenges and advancements in the management of Gorlin syndrome and to provide a new clinical perspective and guidance for future research...
January 31, 2018: Pathophysiology: the Official Journal of the International Society for Pathophysiology
https://www.readbyqxmd.com/read/29437771/hepatotoxicity-associated-with-vismodegib
#15
Prabhjot S Bedi, Manoj P Rai, Nishant Tageja, Heather Laird-Fick
An 82-year-old Caucasian woman with a history of basal cell carcinoma on vismodegib presented with nausea, vomiting and intermittent abdominal pain. Laboratory results were remarkable for the elevation of liver enzymes. Endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiogram (PTC) did not show evidence of intrahepatic or extrahepatic obstruction of the biliary tract. During PTC external biliary catheter was placed; however, bilirubin continued to rise. Further, laboratory work-up and imaging studies ruled out other possible aetiologies for hepatotoxicity such as infections, autoimmune hepatitis and other drugs known to be hepatotoxic thus leaving vismodegib the most likely cause of hepatotoxicity...
February 8, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29417798/neglected-skin-carcinomas-and-vismodegib-our-experience
#16
Filomena Russo, Virginia Mancini, Paolo Taddeucci, Antonietta Cirocco, Francesco Cusano, Michele Pellegrino, Riccardo Sirna
No abstract text is available yet for this article.
February 7, 2018: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://www.readbyqxmd.com/read/29407368/emerging-trends-in-the-treatment-of-advanced-basal-cell-carcinoma
#17
REVIEW
Michael R Migden, Anne Lynn S Chang, Luc Dirix, Alexander J Stratigos, John T Lear
Basal cell carcinoma (BCC) is the most commonly diagnosed skin cancer worldwide. In most patients, BCC can be effectively treated with standard surgical excision, Mohs micrographic surgery, curettage and electrodessication, radiotherapy, and/or superficial field therapies (including 5-fluorouracil, imiquimod, and photodynamic therapy); however, a minority of patients develop advanced BCC, for which treatment can be challenging and outcomes are poorer. Advanced BCC encompasses a heterogeneous assortment of cases, including metastatic BCC as well as locally advanced BCC (for which no formal definition exists but which generally includes large, deep, aggressive, or recurrent tumors)...
March 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29405443/levocarnitine-for-vismodegib-associated-muscle-spasms-a-pilot-randomized-double-blind-placebo-controlled-investigator-initiated-trial
#18
LETTER
J G D Cannon, D C Tran, S Li, A S Chang
No abstract text is available yet for this article.
February 6, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29396391/targeted-inhibition-of-hedgehog-gli-signaling-by-novel-acylguanidine-derivatives-inhibits-melanoma-cell-growth-by-inducing-replication-stress-and-mitotic-catastrophe
#19
Silvia Pietrobono, Roberta Santini, Sinforosa Gagliardi, Francesca Dapporto, David Colecchia, Mario Chiariello, Cosima Leone, Massimo Valoti, Fabrizio Manetti, Elena Petricci, Maurizio Taddei, Barbara Stecca
Aberrant activation of the Hedgehog (HH) signaling is a critical driver in tumorigenesis. The Smoothened (SMO) receptor is one of the major upstream transducers of the HH pathway and a target for the development of anticancer agents. The SMO inhibitor Vismodegib (GDC-0449/Erivedge) has been approved for treatment of basal cell carcinoma. However, the emergence of resistance during Vismodegib treatment and the occurrence of numerous side effects limit its use. Our group has recently discovered and developed novel and potent SMO inhibitors based on acylguanidine or acylthiourea scaffolds...
February 2, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29395868/tumor-architecture-and-notch-signaling-modulate-drug-response-in-basal-cell-carcinoma
#20
Markus Eberl, Doris Mangelberger, Jacob B Swanson, Monique E Verhaegen, Paul W Harms, Marcus L Frohm, Andrzej A Dlugosz, Sunny Y Wong
Hedgehog (Hh) pathway inhibitors such as vismodegib are highly effective for treating basal cell carcinoma (BCC); however, residual tumor cells frequently persist and regenerate the primary tumor upon drug discontinuation. Here, we show that BCCs are organized into two molecularly and functionally distinct compartments. Whereas interior Hh+ /Notch+ suprabasal cells undergo apoptosis in response to vismodegib, peripheral Hh+++ /Notch- basal cells survive throughout treatment. Inhibiting Notch specifically promotes tumor persistence without causing drug resistance, while activating Notch is sufficient to regress already established lesions...
February 12, 2018: Cancer Cell
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