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Topical Rapamycin

Elena Baena-González, Johannes Hanson
SnRK1 (Snf1-related protein kinase 1) and TOR (target of rapamycin) are evolutionarily conserved protein kinases that lie at the heart of energy sensing, playing central and antagonistic roles in the regulation of metabolism and gene expression. Increasing evidence links these metabolic regulators to numerous aspects of plant development, from germination to flowering and senescence. This prompts the hypothesis that SnRK1 and TOR modify developmental programs according to the metabolic status to adjust plant growth to a specific environment...
December 24, 2016: Current Opinion in Plant Biology
Kurt A Escobar, Trisha A VanDusseldorp, Chad M Kerksick
Substantial research has been completed examining the impact of carbohydrate (CHO) intake on endurance exercise, whereas its role in resistance-based exercise performance, adaptation and cell signalling has yet to be fully characterised. This empirical shortcoming has precluded the ability to establish specific CHO recommendations for resistance exercise. This results in recommendations largely stemming from findings based on endurance exercise and/or anecdotal evidence despite the distinct energetic demands and molecular responses mediating adaptation from endurance- and resistance-based exercise...
December 2016: British Journal of Nutrition
Pandiarajan Vignesh, Amit Rawat, Surjit Singh
The genomic revolution in the past decade fuelled by breathtaking advances in sequencing technologies has defined several new genetic diseases of the immune system. Many of these newly characterized diseases are a result of defects in genes involved in immune regulation. The discovery of these diseases has opened a vista of new therapeutic possibilities. Immunomodulatory agents, a hitherto unexplored therapeutic option in primary immunodeficiency diseases have been tried in a host of these newly described maladies...
November 21, 2016: Clinical Reviews in Allergy & Immunology
Mari Wataya-Kaneda, Ayumi Nakamura, Mari Tanaka, Misa Hayashi, Shoji Matsumoto, Koji Yamamoto, Ichiro Katayama
Importance: Inhibitors of mammalian target of rapamycin complex 1, such as sirolimus, effectively target skin lesions in tuberous sclerosis complex (TSC). However, systemic treatment causes adverse effects, and topical sirolimus has shown promise in the treatment of facial angiofibromas. Objective: To evaluate the efficacy, safety, and optimal concentration of a topical sirolimus gel vs placebo for treatment of facial angiofibromas in TSC. Design, Setting, and Participants: A double-blind, placebo-controlled, parallel-group, dose-escalation, phase 2 randomized clinical trial using 3 sirolimus gel concentrations was performed at Osaka University Hospital, Osaka, Japan...
January 1, 2017: JAMA Dermatology
Marta Ivars, Pedro Redondo
No abstract text is available yet for this article.
January 1, 2017: JAMA Dermatology
Cary Crall, Molly Valle, Kush Kapur, Kira A Dies, Marilyn G Liang, Mustafa Sahin, Jennifer T Huang
BACKGROUND/OBJECTIVES: Facial angiofibromas (AF) have the potential to cause disfigurement in children with tuberous sclerosis complex (TSC). Facial disfigurement can impact the quality of life (QoL) of individuals and their families, leading to negative psychosocial outcomes. QoL has not been studied in TSC patients with AF. METHODS: We conducted a cross-sectional survey study to investigate QoL of TSC patients with AF and their caregivers and to explore the current state of access to treatment for AF...
September 2016: Pediatric Dermatology
Teguh H Sasongko, Nur Farrah Dila Ismail, Zamh Zabidi-Hussin
BACKGROUND: Previous studies have shown potential benefits of rapamycin or rapalogs for treating people with tuberous sclerosis complex. Although everolimus (a rapalog) is currently approved by the FDA (U.S. Food and Drug Administration) and the EMA (European Medicines Agency) for tuberous sclerosis complex-associated renal angiomyolipoma and subependymal giant cell astrocytoma, applications for other manifestations of tuberous sclerosis complex have not yet been established. A systematic review is necessary to establish the clinical value of rapamycin or rapalogs for various manifestations in tuberous sclerosis complex...
July 13, 2016: Cochrane Database of Systematic Reviews
Ilaria Dando, Marco Cordani, Massimo Donadelli
Mutations of TP53 gene are the most common feature in aggressive malignant cells. In addition to the loss of the tumor suppressive role of wild-type p53, hotspot mutant p53 isoforms display oncogenic proprieties notoriously referred as gain of functions (GOFs) which result in chemoresistance to therapies, genomic instability, aberrant deregulation of cell cycle progression, invasiveness and enhanced metastatic potential, and finally, in patient poor survival rate. The identification of novel functional oncogenic pathways regulated by mutant p53 represent and intriguing topic for emerging therapies against a broad spectrum of cancer types bearing mutant TP53 gene...
September 2016: IUBMB Life
Silvia Vidali, Jérémy Chéret, Melanie Giesen, Swantje Haeger, Majid Alam, Rachel E B Watson, Abigail K Langton, Matthias Klinger, Jana Knuever, Wolfgang Funk, Barbara Kofler, Ralf Paus
Since it is unknown whether thyroid hormones (THs) regulate mitochondrial function in human epidermis, we treated organ-cultured human skin, or isolated cultured human epidermal keratinocytes, with triiodothyronine (100 pmol/L) or thyroxine (100 nmol/L). Both THs significantly increased protein expression of the mitochondrially encoded cytochrome C oxidase I (MTCO1), complex I activity, and the number of perinuclear mitochondria. Triiodothyronine also increased mitochondrial transcription factor A (TFAM) protein expression, and thyroxine stimulated complex II/IV activity...
October 2016: Journal of Investigative Dermatology
Douglas E Peterson, Joyce A O'Shaughnessy, Hope S Rugo, Sharon Elad, Mark M Schubert, Chi T Viet, Cynthia Campbell-Baird, Jan Hronek, Virginia Seery, Josephine Divers, John Glaspy, Brian L Schmidt, Timothy F Meiller
In recent years oral mucosal injury has been increasingly recognized as an important toxicity associated with mammalian target of rapamycin (mTOR) inhibitors, including in patients with breast cancer who are receiving everolimus. This review addresses the state-of-the-science regarding mTOR inhibitor-associated stomatitis (mIAS), and delineates its clinical characteristics and management. Given the clinically impactful pain associated with mIAS, this review also specifically highlights new research focusing on the study of the molecular basis of pain...
August 2016: Cancer Medicine
Faisal R Ali, Raj Mallipeddi, Emma E Craythorne, Nisith Sheth, Firas Al-Niaimi
Angiofibromas are one of the dermatological hallmarks of tuberous sclerosis. Various ablative treatments have been trialled and more recently topical rapamycin has been proposed. We present our experience of treatment of angiofibromas using carbon dioxide (CO2) laser ablation and provide a timely literature review. Nine patients were retrospectively identified as being treated with CO2 laser between 2009 and 2015. Three patients were male, six were female, median age at first treatment was 28 (range 15-49) years and the median number of treatments was two (range 1-17)...
November 2016: Journal of Cosmetic and Laser Therapy: Official Publication of the European Society for Laser Dermatology
Karin Greveling, Errol P Prens, Martijn B van Doorn
BACKGROUND AND OBJECTIVE: Pulsed Dye Laser (PDL) is currently the gold standard treatment for port wine stains (PWS), although the degree of lesion blanching is variable and often unpredictable. This appears to be due to reformation and reperfusion of blood vessels. Rapamycin has shown potential as an antiangiogenic agent and may prevent the revascularization after PDL treatment. The objective of this study was to evaluate the efficacy of adjuvant use of (commercially available) topical rapamycin after PDL treatment in patients with PWS...
June 20, 2016: Lasers in Surgery and Medicine
Guillaume Bouguéon, Frédéric Lagarce, Ludovic Martin, Hélène Pailhoriès, Guillaume Bastiat, Sandy Vrignaud
Medicines for the treatment of rare diseases frequently do not attract the interest of the pharmaceutical industry, and hospital pharmacists are thus often requested by physicians to prepare personalized medicines. Tuberous Sclerosis Complex (TSC) is a rare disease that causes disfiguring lesions named facial angiofibromas. Various topical formulations of rapamycin (=sirolimus) have been proved effective in treating these changes in small case series. The present study provides for the first time characterization of a 0...
July 25, 2016: International Journal of Pharmaceutics
Sergiusz Jóźwiak, Krzysztof Sadowski, Katarzyna Kotulska, Robert A Schwartz
BACKGROUND: Tuberous sclerosis complex is a genetically determined multisystem disorder that may affect almost any human organ. The discovery of the mammalian target of rapamycin (mTOR) pathway and its involvement in tuberous sclerosis complex-related pathology has led to the introduction of mTOR inhibitors into clinical practice. Topical administration of mTOR inhibitors for skin lesions related to tuberous sclerosis complex may represent a reasonable alternative for more invasive procedures...
August 2016: Pediatric Neurology
Moon Kyung Joo, Jong-Jae Park, Hoon Jai Chun
Signaling pathways of gastric carcinogenesis and gastric cancer progression are being avidly studied to seek optimal treatment of gastric cancer. Among them, hepatocyte growth factor (HGF)/c-MET, phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathways have been widely investigated. Their aberrant expression or mutation has been significantly associated with advanced stage or poor prognosis of gastric cancer...
May 21, 2016: World Journal of Gastroenterology: WJG
Antongiulio Faggiano, Pasqualino Malandrino, Roberta Modica, Daniela Agrimi, Maurizio Aversano, Vincenzo Bassi, Ernesto A Giordano, Valentina Guarnotta, Francesco A Logoluso, Erika Messina, Vincenzo Nicastro, Vincenzo Nuzzo, Marcello Sciaraffia, Annamaria Colao
BACKGROUND: Everolimus, an oral mTOR (mammalian target of rapamycin) inhibitor, is currently approved for the treatment of progressive pancreatic neuroendocrine tumors (NETs). Although promising, only scattered data, often from nondedicated studies, are available for extrapancreatic NETs. PATIENTS AND METHODS: A systematic review of the published data was performed concerning the use of everolimus in extrapancreatic NET, with the aim of summarizing the current knowledge on its efficacy and tolerability...
July 2016: Oncologist
Vishalakshi Viswanath, Parul Thakur, Poonam Pund
INTRODUCTION: Facial angiofibromas (FA) are the most visible cutaneous manifestations in patients with tuberous sclerosis (TS), often resulting in stigmatization of the affected individuals. Recent studies have suggested that topical rapamycin may be an effective treatment for angiofibromas. AIM: To study the safety and efficacy of topical rapamycin in treatment of FA in Type IV-VI skin type. MATERIALS AND METHODS: Five female patients with FA were included in the study, four of whom had TS, whereas one had isolated angiofibromas without systemic involvement...
January 2016: Indian Journal of Dermatology
Ming-Ling Chang
In addition to causing cirrhosis and hepatocellular carcinoma, hepatitis C virus (HCV) is thought to cause hypolipidemia, hepatic steatosis, insulin resistance, metabolic syndrome, and diabetes. The viral life cycle of HCV depends on cholesterol metabolism in host cells. HCV core protein and nonstructural protein 5A perturb crucial lipid and glucose pathways, such as the sterol regulatory element-binding protein pathway and the protein kinase B/mammalian target of rapamycin/S6 kinase 1 pathway. Although several lines of transgenic mice expressing core or full HCV proteins exhibit hepatic steatosis and/or dyslipidemia, whether they completely reflect the metabolic alterations in humans with HCV infection remains unknown...
January 28, 2016: World Journal of Gastroenterology: WJG
Sally E Dickinson, Jaroslav Janda, Jane Criswell, Karen Blohm-Mangone, Erik R Olson, Zhonglin Liu, Christy Barber, Emanuel F Petricoin, Valerie S Calvert, Janine Einspahr, Jesse E Dickinson, Steven P Stratton, Clara Curiel-Lewandrowski, Kathylynn Saboda, Chengcheng Hu, Ann M Bode, Zigang Dong, David S Alberts, G Timothy Bowden
The PI3Kinase/Akt/mTOR pathway has important roles in cancer development for multiple tumor types, including UV-induced nonmelanoma skin cancer. Immunosuppressed populations are at increased risk of aggressive cutaneous squamous cell carcinoma (SCC). Individuals who are treated with rapamycin (sirolimus, a classical mTOR inhibitor) have significantly decreased rates of developing new cutaneous SCCs compared with those that receive traditional immunosuppression. However, systemic rapamycin use can lead to significant adverse events...
March 2016: Cancer Prevention Research
Paolo A Ascierto, Michael Atkins, Carlo Bifulco, Gerardo Botti, Alistair Cochran, Michael Davies, Sandra Demaria, Reinhard Dummer, Soldano Ferrone, Silvia Formenti, Thomas F Gajewski, Claus Garbe, Samir Khleif, Rolf Kiessling, Roger Lo, Paul Lorigan, Grant Mc Arthur, Giuseppe Masucci, Ignacio Melero, Martin Mihm, Giuseppe Palmieri, Giorgio Parmiani, Igor Puzanov, Pedro Romero, Bastian Schilling, Barbara Seliger, David Stroncek, Janis Taube, Sara Tomei, Hassane M Zarour, Alessandro Testori, Ena Wang, Jérôme Galon, Gennaro Ciliberto, Nicola Mozzillo, Francesco M Marincola, Magdalena Thurin
The fourth "Melanoma Bridge Meeting" took place in Naples, December 3-6th, 2014. The four topics discussed at this meeting were: Molecular and Immunological Advances, Combination Therapies, News in Immunotherapy, and Tumor Microenvironment and Biomarkers. Until recently systemic therapy for metastatic melanoma patients was ineffective, but recent advances in tumor biology and immunology have led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS)...
November 30, 2015: Journal of Translational Medicine
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