Modelling the remission of individual acne lesions in vitro

Downie, M.M.T.; Sanders, Deborah A.; Kealey, Terence

doi:10.1046/j.1365-2133.2002.04946.x

Cited by 57 publications

(51 citation statements)

References 35 publications

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“…Preparation of Artificial Skin Sebum, Measurements of Penetration Depth, and Height of the Reaction Products Biological models currently used to investigate phenomena occurring in the pilosebaceous unit are quite complex. [8][9][10] They enable determination of numerous biochemical factors and functions of the unit. In the proposed model, the focus was on differentiating the activity of pure alcoholamines solutions with a potential cleansing effect on the lipid bead of the unit.…”

Section: Methodsmentioning

confidence: 99%

Preliminary Evaluation of Interactions between Selected Alcoholamines and Model Skin Sebum Components

Musiał

Kubiś

2006

CHEMICAL & PHARMACEUTICAL BULLETIN

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Section: Methodsmentioning

confidence: 99%

Preliminary Evaluation of Interactions between Selected Alcoholamines and Model Skin Sebum Components

Musiał

Kubiś

2006

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…[175][176][177] IGF-1 stimulates 5α-reductase, adrenal and gonadal androgen synthesis, AR signal transduction, sebocyte proliferation and lipogenesis. [178][179][180][181][182][183][184] Milk consumption results in a significant increase in IGF-1 serum level and exerts strong insulinotropic effects comparable to high glycaemic food. 185,186 Insulin induces hepatic IGF-1 secretion, and both hormones amplify the stimulatory effect of GH on sebocytes and augment mitogenic downstream signaling pathways of insulin receptors, IGF-1 receptor and FGFR2b (Fig.…”

Section: Interleukin-1α Network In Keratinocytesmentioning

confidence: 99%

“…196 In 3-day sebaceous gland organ cultures, IGF-1 induced 14 C-acetate uptake in a dose-dependent manner indicative for activated lipogenesis. 183 In human SEB-1 sebocytes, IGF-1 has been shown to activate PI3K/Akt and MAPK/ERK-signal transduction pathways. 197 Activation of the PI3K/Akt-pathway by IGF-1 induced SREBP-1 mRNA and -protein and increased sebaceous lipogenesis.…”

Section: Fgfr2b and Igf1r-mediated Activation Of Pi3k/akt Dependent Lmentioning

confidence: 99%

Role of FGFR2-signaling in the pathogenesis of acne

Melnik

2009

Dermato-Endocrinology

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It is the purpose of this review to extend our understanding of the fibroblast growth factor (FGF) receptor-2b-signaling network in the pathogenesis of acne. A new concept of the role of FGFR2b-signaling in dermal-epithelial interaction for skin appendage formation, pilosebaceous follicle homeostasis, comedogenesis, sebaceous gland proliferation and lipogenesis is presented. The FGFR2-gain-of-function mutations in Apert syndrome and unilateral acneiform nevus are most helpful model diseases pointing the way to androgen-dependent dermalepithelial FGFR2-signaling in acne. Androgen-mediated upregulation of FGFR2b-signaling in acne-prone skin appears to be involved in the pathogenesis of acne vulgaris. In organotypic skin cultures, keratinocyte-derived interleukin-1α stimulated fibroblasts to secrete FGF7 which stimulated FGFR2b-mediated keratinocyte proliferation. Postnatal deletion of FGFR2b in mice resulted in severe sebaceous gland atrophy. The importance of FGFR2b in sebaceous gland physiology is further supported by the mode of action of anti-acne agents which have been proposed to attenuate FGFR2b-signaling. Downregulation of FGFR2b-signaling by isotretinoin explains its therapeutic effect in acne. Downregulation of FGFR2b-signaling during the first trimester of pregnancy disturbs branched morphogenesis and explains retinoid embryotoxicity. Insulin-like growth factor-1 (IGF-1), the mediator of growth hormone during puberty, intracts with androgen-dependent FGFR2b-signaling and links androgen-and FGF-mediated signal transduction important in sebaceous gland homeostasis. The search for a follicular defect in the dermalepithelial regulation of growth factor-signaling in acne-prone skin appears to be a most promising approach to clarify the pathogenesis of acne.

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“…So führte an Talgdrüsen in vitro die Addition von EGF zu einer Desorganisation der Keratinozyten und zu einer Ruptur des Infundibulums wie bei schwererer, purulenter Akne [5]. Auf der anderen Seite konnte jedoch an Talgdrüsen in vitro gezeigt werden, dass EGF die Talgproduktion hemmt und eine De-Differenzierung von Sebozyten in einen Keratinozyten-ähnlichen Phänotyp induziert und eine Rolle bei der klinischen Spontanremission von Akneläsionen spielt [3]. In vitro führt EGF an isolierten Haarfollikeln zu einem Übergang von der Anagen-zur Katagenphase des Haarzyklus [12].…”

Section: Introductionunclassified

Schwere Akne unter Therapie eines metastasierten kolorektalen Karzinoms mit monoklonalem Anti-EGF-Rezeptor-Antikörper Cetuximab (Erbitux®)

Kowalzick¹,

Lohse²,

Ziegler³

et al. 2004

Akt Dermatol

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ZusammenfassungSeit kurzem werden Inhibitoren des Rezeptors für epidermalen Wachstumsfaktor (EGF) in der Therapie fortgeschrittener, chemotherapieresistenter Karzinomerkrankungen, wie dem kolorektalen Karzinom und dem nicht-kleinzelligen Bronchialkarzinom eingesetzt. Aus den Zulassungsstudien ist bekannt, dass bei der Mehrzahl der Patienten hierunter Nebenwirkungen am Hautorgan auftreten. Die häufigste kutane Nebenwirkung bei 29 bis 39 % der Patienten ist das Auftreten akneiformer Hauterscheinungen. Wir berichten über einen 64-jährigen Patienten mit metastasiertem kolorektalen Karzinom, das auf die StandardSecond-line-Chemotherapie mit Irinotecan nicht mehr ansprach und daher zusätzlich mit Cetuximab (Erbitux ), einem monoklonalen Antikörper gegen den EGF-Rezeptor behandelt wurde. Während des 2. Therapiezyklus (wöchentliche Applikation) entwickelte er binnen eines Tages massive hochentzündliche Hautveränderungen im Gesicht, den Schultern und in der vorderen und hinteren Schweiûrinne, die morphologisch das Bild einer Acne fulminans erreichten. Noch ohne spezifische Therapie besserte sich das Krankheitsbild spontan bereits nach wenigen Tagen und klang unter symptomatischer Therapie binnen 2 Wochen weitgehend ab. Die enge zeitliche Korrelation der Gabe von EGF-Rezeptor-Antagonisten und dem Auftreten von Akne könnte für eine Rolle des EGF/EGF-Rezeptor-Systems bei der Pathogenese dieser Erkrankung sprechen. AbstractRecently, inhibitors of epidermal growth factor (EGF) receptor were approved by health authorities for treatment of metastastatic carcinomas including colorectal and non-small cell lung carcinoma not responding to standard chemotherapies. It is known from clinical studies that most of the treated patients developed unwanted drug induced side effects of the skin. The cutaneous side effect occurring most frequently is the eruption of acne lesions in 29 to 39 % of the patients treated. We report on a 64 years old male patient with metastatic colorectal carcinoma not responding anymore to standard second line chemotherapy with irinotecan and then additionally was treated with cetuximab (Erbitux ), a monoclonal antibody directed against the EGF receptor. During the second therapy cycle (weekly administrations) he developed within a day severe inflammatory skin lesions of the face, the shoulders, the back and his breast resembling morphologically acne fulminans. Without specific therapy the skin disease improved spontaneously within several days and cleared under symptomatic therapy within 2 weeks. This side effect could lead to the assumption of a role of the EGF/EGF receptor system in the pathogenesis of acne.

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Modelling the remission of individual acne lesions in vitro

Cited by 57 publications

References 35 publications

Preliminary Evaluation of Interactions between Selected Alcoholamines and Model Skin Sebum Components

Preliminary Evaluation of Interactions between Selected Alcoholamines and Model Skin Sebum Components

Role of FGFR2-signaling in the pathogenesis of acne

Schwere Akne unter Therapie eines metastasierten kolorektalen Karzinoms mit monoklonalem Anti-EGF-Rezeptor-Antikörper Cetuximab (Erbitux®)

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