Cutaneous adverse events caused by immune checkpoint inhibitors

Journal of the American Academy of Dermatology, Год журнала: 2021, Номер 85(4), С. 956 - 966

Опубликована: Июль 28, 2021

Язык: Английский

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Safety and Tolerability of Sonic Hedgehog Pathway Inhibitors in Cancer

Drug Safety, Год журнала: 2019, Номер 42(2), С. 263 - 279

Опубликована: Янв. 16, 2019

Язык: Английский

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Novel Targeted Therapies for Metastatic Thyroid Cancer—A Comprehensive Review

Cancers, Год журнала: 2020, Номер 12(8), С. 2104 - 2104

Опубликована: Июль 29, 2020

The knowledge on thyroid cancer biology has grown over the past decade. Thus, diagnostic and therapeutic strategies to manage are rapidly evolving. With new insights into tumor genetics, several novel therapies have been approved for treatment of cancer. Tyrosine kinase inhibitors (TKIs), such as lenvatinib sorafenib, successfully utilized radioactive iodine (RAI)-refractory metastatic differentiated (DTC). In addition, pretreatment with mitogen-activated protein (MAPK) (trametinib selumetinib) shown restore RAI avidity in previously RAI-refractory DTCs. Local therapies, external beam radiation radiofrequency/ethanol ablation, also employed DTC. Vandetanib cabozantinib two TKIs currently by Food Drug Administration (FDA) medullary (MTC). Other peptide receptor radionuclide therapy carcinoembryonic antigen (CEA) vaccine, treating MTC. Ongoing trials selective rearranged-during-transfection (RET) protooncogene inhibitors, LOXO-292 BLU-667, demonstrated promising results MTC resistant non-selective TKIs. FDA-approved BRAF/MEK inhibitor combination dabrafenib trametinib revolutionized BRAFV600E mutation positive anaplastic Several other emerging classes medications, gene fusion immune checkpoint being actively investigated clinical trials. this review, we describe molecular landscape targeted combinations available

Язык: Английский

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Ocular adverse events associated with immune checkpoint inhibitors, a scoping review

Journal of Ophthalmic Inflammation and Infection, Год журнала: 2023, Номер 13(1)

Опубликована: Фев. 22, 2023

Abstract Introduction Immune checkpoint inhibitors (ICIs) have become an important part of the treatment multiple cancers, especially for advanced melanoma and non-small cell lung cancer. Some tumors are capable escaping immunosurveillance by stimulating checkpoints on T-cells. ICIs prevent activation these thereby stimulate immune system indirectly anti-tumor response. However, use is associated with various adverse events. Ocular side effects rare but may a major impact quality life patient. Methods A comprehensive literature search medical databases Web Science, Embase PubMed was performed. Articles that provided description case report containing 1) cancer patient(s) treated (a combination of) inhibitors, 2) assessed occurrence ocular events, were included. total 290 reports Results Melanoma ( n = 179; 61.7%) 56; 19.3%) most frequent reported malignancies. The primary used nivolumab 123; 42.5%) ipilimumab 116; 40.0%). Uveitis common event 134; 46.2%) mainly related to melanoma. Neuro-ophthalmic disorders, including myasthenia gravis cranial nerve second events 71; 24.5%), Adverse affecting orbit cornea in 33 (11.4%) 30 cases (10.3%) respectively. concerning retina 26 (9.0%). Conclusion aim this paper provide overview all ICIs. insights retrieved from review might contribute better understanding underlying mechanisms Particularly, difference between actual immune-related paraneoplastic syndromes be relevant. These findings great value establishing guidelines how manage

Язык: Английский

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Study on mechanism of Spatholobi Caulis in the treatment of the hand-foot skin reaction induced by targeted drug therapy based on network pharmacology and molecular docking: An observational study

Medicine, Год журнала: 2025, Номер 104(2), С. e41085 - e41085

Опубликована: Янв. 10, 2025

Based on network pharmacology and molecular docking methods, this study explored its active compounds confirmed potential mechanism of action against Hand-foot skin reaction induced by tumor-targeted drugs. Traditional Chinese Medicine Systems Pharmacology Database Analysis Platform UniProt were used to obtain the ingredients target proteins Spatholobi Caulis. All hand-foot (HFSR)-related targets obtained with help Human Gene Database, Online Mendelian Inheritance in Humans (OMIM), DisGeNET DrugBank databases. Cytoscape 3.7.1 software was construct ingredient-target visualization Caulis, common Caulis HFSR. And through BisoGenet plug-in Cytoscape, PPI topology analysis performed. The Metescape database online mapping tool platform for Ontology (GO) function Kyoto Encyclopedia Genes Genomes (KEGG) pathway enrichment identify key pathways Finally, Autodock Vina PyMol 2.5 verification. There 24 components 244 genes, 1635 disease-related 51 genes reaction, included NTRK1, epidermal growth factor receptor (EGFR), APP, TP53, HSP90AB1, HSP90AA, CUL3, etc. GO functional involved a total 66 functions, 39 cellular components, 817 biological processes. KEGG found 154 related signaling pathways, mainly enriched Pathways cancer, cytomegalovirus infection, Kaposi arcoma-associated herpesvirus panic EGFR tyrosine kinase inhibitor resistance, P13K-Akt pathway, Proteoglycans HIF-1 Ras Molecular results showed that luteolin, component had high affinity EGFR. Medicagol, is proved lung cancer targeted therapy regulating multiple It treatment has characteristics multi-component, multi-target multi-pathway regulation.

Язык: Английский

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Cutaneous Complications of Targeted Melanoma Therapy

Current Treatment Options in Oncology, Год журнала: 2016, Номер 17(11)

Опубликована: Сен. 19, 2016

Язык: Английский

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A clinical and biological review of keratoacanthoma*

British Journal of Dermatology, Год журнала: 2021, Номер 185(3), С. 487 - 498

Опубликована: Апрель 17, 2021

Keratoacanthoma (KA) is a common skin tumour that remains controversial regarding classification, epidemiology, diagnosis, prognosis and management. Classically, KA manifests as rapidly growing, well-differentiated, squamoid lesion with predilection for sun-exposed sites in elderly people tendency to spontaneously regress. Historically, KAs have been considered variant of cutaneous squamous cell carcinoma (cSCC) are often reported KA-type cSCC. However, the penchant regression has led many categorize biologically benign tumours distinct pathophysiological mechanisms from malignant The clinical histopathological similarities between cSCC, particularly well-differentiated made definitive differentiation difficult or impossible cases. ambiguity entities general recommendation surgical excision ensure potentially cSCC not left untreated. This current standard creates unnecessary morbidity financial strain patients, especially at-risk population. There no reports death date, while an approximate mortality rate 1·5%. Reliably distinguishing would shift management strategies towards less-invasive treatment modalities, prevent morbidity, likely reduce associated healthcare costs. Herein, we review pathophysiology characteristics KA, conclude on balance evidence

Язык: Английский

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Drugs and the skin: A concise review of cutaneous adverse drug reactions

British Journal of Clinical Pharmacology, Год журнала: 2022, Номер 90(8), С. 1838 - 1855

Опубликована: Авг. 17, 2022

Drug-induced skin disease or cutaneous adverse drug reactions (CADRs) are terms that encompass the clinical manifestations of skin, mucosae and adnexa induced by a its metabolites. The is organ most frequently affected reactions, which may affect up to 10% hospitalized patients occur in 1-3% multimedicated patients. Most CADRs mild self-resolving conditions; however, 2-6.7% could develop into potentially life-threatening conditions. represent heterogeneous field can be diagnostically challenging as they mimic any dermatosis. Currently, there between 29-35 different drug-reaction patterns reported ranging from dermatitis an extensively burnt patient. maculopapular rash, urticaria/angioedema, fixed eruption erythema multiforme. Less common but more severe include erythroderma, reaction with eosinophilia systemic symptoms, Stevens-Johnson syndrome/toxic epidermal necrolysis spectrum. Almost induce CADR, antibiotics, nonsteroidal anti-inflammatory drugs antiepileptics involved. Different mechanisms involved pathogenesis CADRs, although some cases, these remain still unknown. classified ways: (i) type A (augmented) B (bizarre); (ii) immediate delayed; (iii) immune-mediated nonimmune-mediated; (iv) nonsevere life-threatening; (v) their phenotype, including exanthematous, urticarial, pustular blistering morphology. Recognizing specific CADR will mostly depend on ability physician perform detailed examination, proper description morphology lesions supporting laboratory and/or biopsy findings.

Язык: Английский

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TNF stimulates IL‐6, CXCL8 and VEGF secretion from human keratinocytes via activation of mTOR, inhibited by tetramethoxyluteolin

Experimental Dermatology, Год журнала: 2017, Номер 27(2), С. 135 - 143

Опубликована: Ноя. 4, 2017

Psoriasis is an autoimmune skin disease characterized by keratinocyte hyperproliferation and chronic inflammation. The pathogenesis of psoriasis involves proinflammatory cytokines, such as tumor necrosis factor (TNF), but the mechanism activation not well understood. Here, we show that TNF (10 or 50 ng/mL) stimulates a significant (P < .0001) gene expression secretion IL-6, CXCL8 VEGF from both cultured human HaCaT normal epidermal keratinocytes (NHEKs). This effect occurs via mammalian target rapamycin (mTOR) signalling complex shown Western blot analysis phospho-ELISAs. Pretreatment with novel natural flavonoid tetramethoxyluteolin (10-100 μmol L-1 ) significantly inhibits all 3 mediators in concentration-dependent manner. Moreover, (50 appears to be potent inhibitor phosphorylated mTOR substrates (pmTORSer2448 , pp70S6KThr389 p4EBP1Thr37/46 compared known inhibitors keratinocytes. present findings indicate inflammation signalling. Inhibition may used treatment for psoriasis.

Язык: Английский

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Systemic Therapies for Advanced Melanoma

Dermatologic Clinics, Год журнала: 2019, Номер 37(4), С. 409 - 423

Опубликована: Июль 10, 2019

Язык: Английский

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