Treatment of psoriasis with topical sirolimus: preclinical development and a randomized, double-blind trial

Ormerod, Anthony; Shah, S A; Copeland, Paul M.; Omar, Ghada A; Winfield, A. J.

doi:10.1111/j.1365-2133.2005.06438.x

Cited by 97 publications

(76 citation statements)

References 22 publications

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“…Ormerod et al studied the effect of 2.2% sirolimus in patients with chronic psoriasis areas. They observed a significant decrease in the number of proliferating epidermal cells after 6 weeks and after another 6 weeks the drop was 8% [32]. Some other authors have also noted a decrease in the Ki-67 index in the course of systemic psoriasis treatment, e.g.…”

Section: Discussionmentioning

confidence: 90%

Influence of phototherapy in psoriasis on ki-67 antigen expression: a preliminary study

Jesionek-Kupnicka

Chomiczewska-Skóra²,

Rotsztejn³

2013

pjp

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Antigen Ki-67 is a non-histone nuclear protein, closely connected with cell proliferation. Determining Ki-67 allows for a quick and reliable evaluation of the growth fraction of the studied cell population. It serves as a marker of proliferative activity in neoplasms and other diseases with excessive cell proliferation such as psoriasis. Evaluation of Ki-67 expression in epidermal cells was performed in 10 individuals suffering from plaque psoriasis, before and after one of three methods of phototherapy: broadband UVB, narrowband UVB or PUVA. We observed increased Ki-67 antigen expression in psoriatic lesions. The percentage of Ki-67 positive nuclei in the epidermis affected by the disease ranged from 0 to 30% and in the macroscopically healthy surrounding tissue the percentage was from 0 to 10%. After phototherapy the expression in lesional skin decreased (p < 0.01). The greatest decrease was observed after the application of PUVA therapy (from 25 to 10% of cells, p < 0.05). No significant differences were observed in the perilesional skin with regard to Ki-67 antigen expression before or after phototherapy. On the basis of our own study and studies conducted by other researchers, it can be concluded that reduced Ki-67 expression after the application of PUVA and UVB therapies in the psoriatic epidermis is not a characteristic result of phototherapy only. It is a characteristic property of any effective psoriasis therapy.

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Section: Discussionmentioning

confidence: 90%

Influence of phototherapy in psoriasis on ki-67 antigen expression: a preliminary study

Jesionek-Kupnicka

Chomiczewska-Skóra²,

Rotsztejn³

2013

pjp

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“…mTOR inhibitors may offer a range of new therapeutic options for psoriasis patients. Clinical trials indicated that rapamycin, the prototypical mTOR inhibitor could significantly reduce the clinical score of psoriasis when treating psoriasis patients (Ormerod et al, 2005;Reitamo et al, 2001). Everolimus, a semisynthetic macrolide and a member of the mTOR inhibitors family, could lead to the resolution of recalcitrant psoriatic manifestations (Frigerio et al, 2007;Wei & Lai, 2015).…”

Section: Discussionmentioning

confidence: 99%

Metformin inhibits proliferation and proinflammatory cytokines of human keratinocytesin vitrovia mTOR-signaling pathway

Liu

Yang

et al. 2015

Pharmaceutical Biology

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Context: The antidiabetic drug metformin exhibits antiproliferative and pro-apoptotic effects in various cells, suggesting its potential to treat a variety of malignant and non-malignant hyperplastic diseases. Clinical studies indicate that psoriasis patients with metformin treatment have a better response than those without metformin. Objective: The present study evaluates the antiproliferative activity and anti-inflammatory responses of metformin in human keratinocytes in vitro and explores the underlying mechanisms. Materials and methods: HaCaT cells were incubated with metformin at 0, 25, 50, and 100 mM for 48 h. Antiproliferative activity was evaluated by MTT and apoptotic response was examined by flow cytometry. ELISA was used to detect IL-6, TNF-a, and VEGF protein expression. Western blot was used to investigate the expression of the mammalian target of rapamycin (mTOR) and its downstream effectors p70 ribosomal S6 kinase (p70S6K). Results: The survival rates of HaCaT cells treated with metformin at 50 mM were reduced to 75.6, 59.4, and 30.3% at 24, 48, and 72 h, respectively. The number of apoptotic HaCaT cells was significantly increased at 50 mM metformin after 48 h treatment. Metformin can exert an antiinflammatory effect by direct inhibition of IL-6, TNF-a, and VEGF. Metformin at 50 mM significantly reduced the phosphorylation of mTOR and p70S6K, by 49.0 and 62.1%, respectively. Discussion and conclusion: Metformin treatment significantly inhibited proliferation and proinflammatory responses in HaCaT cells by a mechanism associated with inhibition of the mTOR signaling pathway. The results indicate that metformin may be used as a potential therapeutic agent for psoriasis.

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“…1,3 It was found to be active against several strains of yeast and fungi. However, no activity was observed against gram-positive or gram-negative bacteria.…”

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confidence: 99%

Sirolimus (rapamycin): From the soil of Easter Island to a bright future

Paghdal

Schwartz

2007

Journal of the American Academy of Dermatology

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Treatment of psoriasis with topical sirolimus: preclinical development and a randomized, double-blind trial

Abstract: Topically applied sirolimus penetrates normal skin and may have some antipsoriatic and immunosuppressive activity.

Cited by 97 publications

References 22 publications

Influence of phototherapy in psoriasis on ki-67 antigen expression: a preliminary study

Influence of phototherapy in psoriasis on ki-67 antigen expression: a preliminary study

Metformin inhibits proliferation and proinflammatory cytokines of human keratinocytesin vitrovia mTOR-signaling pathway

Sirolimus (rapamycin): From the soil of Easter Island to a bright future

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