Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Facial angiofibromas are the most visible and unsightly of all the cutaneous manifestations of tuberous sclerosis (TSC). A 17-year-old female, a known case of TSC, presented for the treatment of cosmetically disfiguring facial angiofibromas. She was started on twice daily application of 0.1% sirolimus ointment prepared from crushed tablets of sirolimus compounded in white soft paraffin. After 3 months of use, there was visible decrease in the erythema and the size of the angiofibromas. In an attempt to accelerate the response, the concentration was further increased to 1% sirolimus which was used for a month, resulting in a decrease not only in the size and redness but also in the number of the angiofibromas. The patient did not experience any cutaneous or systemic complications related to therapy. Sirolimus belongs to a novel class of anticancer drugs known as mTOR (mammalian target of Rapamycin) inhibitors. Sirolimus has been used as a targeted therapy for the renal and neurological manifestations of TSC. Topical preparation of sirolimus is not commercially available till date and hence preparations from crushed tablets or oral solution of sirolimus have been used with beneficial effects in treatment of angiofibromas especially in younger patients with flatter lesions. Randomized controlled trials are necessary to enable us to confirm the efficacy, long-term safety, the optimal dosage and possibility of reappearance once the drug is withdrawn. This is possibly the first case report of the use of topical sirolimus in India.
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PMID:Facial angiofibromas of tuberous sclerosis treated with topical sirolimus in an Indian patient. 2611 57

Ultraviolet radiation is an important etiologic factor in skin cancer and a better understanding of how solar stimulated light (SSL) affects signal transduction pathways in human skin which is needed in further understanding activated networks that could be targeted for skin cancer prevention. We utilized Reverse Phase Protein Microarray Analysis (RPPA), a powerful technology that allows for broad-scale and quantitative measurement of the activation/phosphorylation state of hundreds of key signaling proteins and protein pathways in sun-protected skin after an acute dose of two minimal erythema dose (MED) of SSL. RPPA analysis was used to map the altered cell signaling networks resulting from acute doses of solar simulated radiation (SSL). To that end, we exposed sun-protected skin in volunteers to acute doses of two MED of SSL and collected biopsies pre-SSL and post-SSL irradiation. Frozen biopsies were subjected to laser capture microdissection (LCM) and then assessed by RPPA. The activation/phosphorylation or total levels of 128 key signaling proteins and drug targets were selected for statistical analysis. Coordinate network-based analysis was performed on specific signaling pathways that included the PI3k/Akt/mTOR and Ras/Raf/MEK/ERK pathways. Overall, we found early and sustained activation of the PI3K-AKT-mTOR and MAPK pathways. Cell death and apoptosis-related proteins were activated at 5 and 24 h. Ultimately, expression profile patterns of phosphorylated proteins in the epidermal growth factor receptor (EGFR), AKT, mTOR, and other relevant pathways may be used to determine pharmacodynamic activity of new and selective topical chemoprevention agents administered in a test area exposed to SSL to determine drug-induced attenuation or reversal of skin carcinogenesis pathways.
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PMID:Protein activation mapping of human sun-protected epidermis after an acute dose of erythemic solar simulated light. 2916 24

Nutrition plays a critical role in the manifestation and management of inflammatory pilosebaceous disorders. There is rich potential for insight into the impact of dietary effects on the pathophysiology of inflammatory pilosebaceous disorders including acne vulgaris, hidradenitis suppurativa, rosacea, and the closely related seborrhoeic dermatitis. Acne vulgaris and hidradenitis suppurativa are thought to have similar diet-modulating pathogenic pathways. Western diet influences Acne vulgaris and hidradenitis suppurativa by increasing insulin and modulating FOX01/mTOR, resulting in over-expression of cytokeratins, hyperproliferation of keratinocytes, and hypercornification of the follicular wall. Key receptors in rosacea are alternatively activated by UV radiation, hot beverages, spicy foods, vanilla, cinnamon, caffeine, alcohol, cold temperatures, and niacin- and formalin-containing foods, to increase oedema and flushing, resulting in erythema, telangiectasia, and warmth, characteristic features of the condition. Seborrhoeic dermatitis, while not a follicular disorder, is closely related, and can be modulated by dietary influences, such as biotin and probiotics. This overview summarizes the role that nutrition plays on these disorders, and identifies dietary modifications as potential adjunctive therapies.
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PMID:The role of nutrition in inflammatory pilosebaceous disorders: Implication of the skin-gut axis. 3017 43

Many studies have investigated cutaneous reactions to antitumor drugs and found them to be quite numerous. We describe drug eruptions that may be associated with different therapies by class: antimetabolite chemotherapeutics, genotoxic agents, spindle inhibitors, signal transduction inhibitors, and immunotherapies. Methotrexate is most often associated with mucocutaneous reactions, alkylating antimetabolite agents with hyperpigmentation, and platinum antimetabolite agents with type I IgE-mediated hypersensitivity reactions. Anthracycline derivatives can induce the hand-foot syndrome in patients, and bleomycin is associated with a bleomycin-induced flagellate erythema. Taxane spindle inhibitors can result in acneiform eruptions, which may also be seen with use of epidermal growth factor receptor inhibitors. Imatinib and its derivatives can cause a truncal maculopapular eruption, whereas multikinase inhibitors can produce a hand-foot-skin reaction. Vemurafenib can result in squamous cell carcinomas and photosensitivity. First-generation mammalian target of rapamycin inhibitors may cause a maculopapular eruption initially involving the face and neck. Programmed death (PD)-1-ligand and receptor inhibitors are associated with bullous pemphigoid. Ipilimumab, targeting Cytotoxic -T- Lymphocyte- associated (CTLA-4) receptors, can cause a morbilliform reaction, whereas Interleukin -2 (IL-2) analogs can create the capillary leak syndrome. Chemotherapeutic drug eruptions classically can manifest in the aforementioned ways; however, it is important to understand that they are associated with myriad cutaneous adverse effects, which may be mistaken for organic skin disease. Oncologists prescribing these medications should be familiar with the cutaneous side effects of these medications, and so they may counsel patients to be on the lookout for them.
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PMID:Drug eruptions associated with tumor therapy: Great imitators. 3251

Glucagonoma is a hormonally active rare pancreatic neuroendocrine tumour causing an excess of glucagon. This is a narrative review based on a multidisciplinary approach of the tumour. Typically associated dermatosis is necrolytic migratory erythema (NME) which is most frequently seen at disease onset. Insulin-dependent diabetes mellitus, depression, diarrhoea, deep vein thrombosis are also identified, as parts of so-called 'D' syndrome. Early diagnosis is life saving due to potential aggressive profile and high risk of liver metastasis. NME as paraneoplastic syndrome may be present for months and even years until adequate recognition and therapy; it is remitted after successful pancreatic surgery. Thus the level of practitioners' awareness is essential. If surgery is not curative, debulking techniques may improve the clinical aspects and even the outcome in association with other procedures such as embolization of hepatic metastasis; ablation of radiofrequency type; medical therapy including chemotherapy, targeted therapy with mTOR inhibitors such as everolimus, PRRT (peptide receptor radiotherapy), and somatostatin analogues (including combinations of medical treatments). Increased awareness of the condition involves multidisciplinary practitioners.
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PMID:Glucagonoma: From skin lesions to the neuroendocrine component (Review). 3290 95