Gemcitabine-induced skin necrosis

Haydock, Maria Monica; Sigdel, Saroj; Pacioles, Toni

doi:10.1177/2050313x18809268

Cited by 8 publications

(12 citation statements)

References 12 publications

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“…Other cutaneous adverse reactions that have been reported include bullous dermatosis, pseudocellulitis, subacute cutaneous lupus, alopecia, and palmar-plantar erythrodysesthesia. 7 However, in our review of the available literature, autoimmune bullous diseases caused by gemcitabine have not been reported.…”

Section: Discussionmentioning

confidence: 90%

Pemphigus Herpetiformis-Type Drug Reaction Caused by Programmed Cell Death Protein-1 Inhibitor Treatment

Zhang

Zhang²,

Xie³

et al. 2021

CCID

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Reports of immune-related adverse events caused by programmed cell death protein-1 inhibitor are becoming increasingly frequent. Herein, we report the first case of pemphigus herpetiformis-type drug reaction presented after the treatment of tislelizumab (6 cycles) in a primary non-small cell lung carcinoma patient. A 56-year-old Chinese man was referred to our department for pruritic annulare erythema and blister for two weeks. Histological finding revealed blister formation in the epidermis and eosinophilic infiltration in the blister fluid. Direct immunofluorescence showed intercellular deposition of IgG and C3 within the lower part of epidermis. Serum anti-intercellular antibodies were positive at 1:100 dilution. Based on history and clinicopathological correlation, herpetiformis-type drug-induced pemphigus was diagnosed, which was possibly be induced by tislelizumab. To the best to our knowledge, there is no report of pemphigus herpetiformis-type drug-induced reaction associated with programmed cell death protein-1 inhibitor treatment.

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Section: Discussionmentioning

confidence: 90%

Pemphigus Herpetiformis-Type Drug Reaction Caused by Programmed Cell Death Protein-1 Inhibitor Treatment

Zhang

Zhang²,

Xie³

et al. 2021

CCID

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“…Though GEM is preferred as a first-line treatment for pancreatic cancer, its enzymatic plasma deaminase decreases its half-life to 8 to 17 min [20]; that demands an increase in drug-dose which would lead towards probable side effects. Common side effects associated with GEM include: black/tarry stools or blood in urine/stools, bleeding gums, swelling of the face and other parts of body, vision issues, chest pain, cough, diarrhea, dizziness, fever, headache, burning, crawling, itching, numbness, difficulty in swallowing, joint pain, pale skin, paralysis, ulcers, sore throat, trouble sleeping, tiredness/weakness, and weight loss [21].…”

Section: Gemcitabine—a Gold Standard Chemotherapeutic Agent For Pamentioning

confidence: 99%

Gemcitabine Combination Nano Therapies for Pancreatic Cancer

et al. 2019

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Pancreatic cancer is one of the deadliest causes of cancer-related death in the United States, with a 5-year overall survival rate of 6 to 8%. These statistics suggest that immediate medical attention is needed. Gemcitabine (GEM) is the gold standard first-line single chemotherapy agent for pancreatic cancer but, after a few months, cells develop chemoresistance. Multiple clinical and experimental investigations have demonstrated that a combination or co-administration of other drugs as chemotherapies with GEM lead to superior therapeutic benefits. However, such combination therapies often induce severe systemic toxicities. Thus, developing strategies to deliver a combination of chemotherapeutic agents more securely to patients is needed. Nanoparticle-mediated delivery can offer to load a cocktail of drugs, increase stability and availability, on-demand and tumor-specific delivery while minimizing chemotherapy-associated adverse effects. This review discusses the available drugs being co-administered with GEM and the limitations associated during the process of co-administration. This review also helps in providing knowledge of the significant number of delivery platforms being used to overcome problems related to gemcitabine-based co-delivery of other chemotherapeutic drugs, thereby focusing on how nanocarriers have been fabricated, considering the modes of action, targeting receptors, pharmacology of chemo drugs incorporated with GEM, and the differences in the physiological environment where the targeting is to be done. This review also documents the focus on novel mucin-targeted nanotechnology which is under development for pancreatic cancer therapy.

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“…In particular, topical use of chemotherapy has also been employed in the treatment of skin conditions such as non‐melanoma skin cancer, actinic keratoses, and skin aging 4,5 . However, often these drugs are associated with adverse side effects, including localized skin eruptions and necrosis as well as systemic pathologies, including ototoxicity and neutropenia 6–11 . Gemcitabine is one of the commonly used chemotherapy drugs, which has been used either alone, or in combination with other antineoplastic agents for the treatment of malignancies, including pancreatic cancer, non‐small cell lung cancer, intrahepatic cholangiocarcinoma, colorectal cancer, ovarian cancer, breast cancer, and melanoma 12–18 .…”

Section: Introductionmentioning

confidence: 99%

“…29,30 Notably, MVPs are small nano-sized cellular bodies of $100-1000 nm diameter that are released from a wide variety of cell types via exocytosis in response to various stimuli, including anticancer agents, and serve to mediate cell-to-cell communications, both in physiological and pathological conditions. [29][30][31] Given that gemcitabine is a potential drug of clinical interest, yet associated with adverse events such as skin rash/necrosis, 9,10 and that it can be absorbed through the skin via processes, including passive diffusion, 32 we sought to determine if topical treatment of gemcitabine would stimulate MVP release containing PAF agonists, and define the associated mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Topical application of gemcitabine generates microvesicle particles in human and murine skin

et al. 2022

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Chemotherapy has remained the mainstay for the treatment of multiple types of cancers. In particular, topical use of chemotherapy has been used for skin cancers. Though effective, topical chemotherapy has been limited due to adverse effects such as local and even systemic toxicities. Our recent studies demonstrated that exposure to pro-oxidative stressors, including therapeutic agents induces the generation of extracellular vesicles known as microvesicle particles (MVP) which are dependent on activation of the Platelet-activating factor-receptor (PAFR), a G-protein coupled receptor present on various cell types, and acid sphingomyelinase (aSMase), an enzyme required for MVP biogenesis. Based upon this premise, we tested the hypothesis that topical application of gemcitabine will induce MVP generation in human and murine skin. Our ex vivo studies using human skin explants demonstrate that gemcitabine treatment results in MVP generation in a dose-dependent manner in a process blocked by PAFR antagonist and aSMase inhibitor. Importantly, gemcitabineinduced MVPs carry PAFR agonists. To confirm the mechanisms, we employed PAFR-expressing and deficient (Ptafr À/À ) mouse models as well as mice deficient in aSMase enzyme (Spmd1 À/À ). Similar to the findings using pharmacologic tools, genetic-based approaches demonstrate that gemcitabine-induced

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Gemcitabine-induced skin necrosis

Cited by 8 publications

References 12 publications

Pemphigus Herpetiformis-Type Drug Reaction Caused by Programmed Cell Death Protein-1 Inhibitor Treatment

Pemphigus Herpetiformis-Type Drug Reaction Caused by Programmed Cell Death Protein-1 Inhibitor Treatment

Gemcitabine Combination Nano Therapies for Pancreatic Cancer

Topical application of gemcitabine generates microvesicle particles in human and murine skin

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