Mitochondrial oxidative stress as a novel therapeutic target to overcome intrinsic drug resistance in melanoma cell subpopulations.

Abstract:

:Despite recent success in melanoma therapy, most patients with metastatic disease still undergo deadly progression. We have identified a novel mechanism of multidrug resistance allowing a small subpopulation of slow-cycling melanoma cells to survive based on elevated oxidative bioenergy metabolism. In this study, we asked whether such slow-cycling cells could be eliminated by co-treatment with the copper-chelator elesclomol. Elesclomol-copper complexes can cause oxidative stress by disruption of the mitochondrial respiration chain or by indirect non-mitochondrial induction of reactive oxygen species. We have found that elesclomol effectively kills the slow-cycling subpopulation and prevents the selective enrichment for slow-cycling cells, which usually results after monotreatment. We hypothesize that elesclomol could overcome the multidrug resistance of slow-cycling melanoma cells and prevent tumor repopulation in melanoma patients in future.

journal_name

Exp Dermatol

journal_title

Experimental dermatology

authors

Cierlitza M,Chauvistré H,Bogeski I,Zhang X,Hauschild A,Herlyn M,Schadendorf D,Vogt T,Roesch A

doi

10.1111/exd.12613

subject

Has Abstract

pub_date

2015-02-01 00:00:00

pages

155-7

issue

2

eissn

0906-6705

issn

1600-0625

journal_volume

24

pub_type

信件
  • CCL7 contributes to the TNF-alpha-dependent inflammation of lesional psoriatic skin.

    abstract::Chemokines are small chemotactic proteins that have a crucial role in leukocyte recruitment into tissue. Targeting these mediators has been suggested as a potential therapeutic option in inflammatory skin diseases such as psoriasis. Using quantitative RT-PCR, we found CCL7, a chemokine ligand known to interact with mu...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/exd.12709

    authors: Brunner PM,Glitzner E,Reininger B,Klein I,Stary G,Mildner M,Uhrin P,Sibilia M,Stingl G

    更新日期:2015-07-01 00:00:00

  • Human hair follicle organ culture: theory, application and perspectives.

    abstract::For almost a quarter of a century, ex vivo studies of human scalp hair follicles (HFs) have permitted major advances in hair research, spanning diverse fields such as chronobiology, endocrinology, immunology, metabolism, mitochondrial biology, neurobiology, pharmacology, pigmentation and stem cell biology. Despite thi...

    journal_title:Experimental dermatology

    pub_type: 杂志文章,评审

    doi:10.1111/exd.12836

    authors: Langan EA,Philpott MP,Kloepper JE,Paus R

    更新日期:2015-12-01 00:00:00

  • Pentoxifylline reduces the formation of sunburn cells.

    abstract::Irradiation with ultraviolet (UV) B light results in the formation of apoptotic keratinocytes called sunburn cells (SC). Although generation of SC appears to be one of the most characteristic features of UV-induced skin damage and has been a well-known phenomenon for a long time, the mechanisms involved are not quite ...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/j.1600-0625.1997.tb00138.x

    authors: Schwarz A,Mahnke K,Luger TA,Schwarz T

    更新日期:1997-02-01 00:00:00

  • Antipsoriatic drug anthralin induces EGF receptor phosphorylation in keratinocytes: requirement for H(2)O(2) generation.

    abstract::Even though anthralin is a well-established topical therapeutic agent for psoriasis, little is known about its effects and biochemical mechanisms of signal transduction. In contrast to a previous report, we found that anthralin induced time- and concentration-dependent phosphorylation of epidermal growth factor recept...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/j.0906-6705.2004.00119.x

    authors: Peus D,Beyerle A,Vasa M,Pott M,Meves A,Pittelkow MR

    更新日期:2004-02-01 00:00:00

  • What is new in the psychology of chronic itch?

    abstract::Itch is often regarded as unpleasant or bothersome and is accompanied by symptoms of distress and impairments in daily life. The biopsychosocial model of chronic itch describes how psychological factors can contribute to the improvement or exacerbation of chronic itch and related scratching behaviour. Recent research ...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/exd.13992

    authors: Evers AWM,Peerdeman KJ,van Laarhoven AIM

    更新日期:2019-12-01 00:00:00

  • Molecular imaging reveals time course of matrix metalloproteinase activity in acute cutaneous vasculitis in vivo.

    abstract::Matrix metalloproteinases (MMPs) play a critical role in various pathological conditions including cutaneous inflammation. Thus far, serial assessment of MMP activity in ongoing inflammation is hampered due to technical limitations. Here, we present an innovative method for longitudinal detection of MMP activity by in...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/exd.12253

    authors: Steingräber AK,Schelhaas S,Faust A,Jacobs AH,Schäfers M,Goerge T

    更新日期:2013-11-01 00:00:00

  • Inhibiting scar formation in vitro and in vivo by adenovirus-mediated mutant Smad4: a preliminary report.

    abstract::The best characterized signalling pathway employed by transforming growth factor-beta (TGF-β) is the Smad pathway. We focused on Smad4, because it is essential for the activation of Smad-dependent target genes. We aimed to explore the possibility of inhibiting scar formation after wounding by blocking TGF-β signalling...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/j.1600-0625.2010.01186.x

    authors: Tan WQ,Gao ZJ,Xu JH,Yao HP

    更新日期:2011-02-01 00:00:00

  • A reappraisal of the use of 5-methoxypsoralen in the therapy of psoriasis.

    abstract::5-methoxypsoralen (5-MOP) is considered an alternative to 8-methoxypsoralen (8-MOP) for photochemotherapy of psoriasis. We have compared the clinical efficacy and tolerability of 5-MOP (1.2 mg/kg)-UVA versus 8-MOP (0.6 mg/kg)-UVA therapy in 25 patients of skin type III and IV, affected by relapsing plaque-type psorias...

    journal_title:Experimental dermatology

    pub_type: 临床试验,杂志文章

    doi:10.1111/j.1600-0625.1992.tb00071.x

    authors: Calzavara-Pinton P,Ortel B,Carlino A,Honigsmann H,De Panfilis G

    更新日期:1992-07-01 00:00:00

  • Regenerative healing, scar-free healing and scar formation across the species: current concepts and future perspectives.

    abstract::All species have evolved mechanisms of repair to restore tissue function following injury. Skin scarring is an inevitable and permanent endpoint for many postnatal organisms except for non-amniote vertebrates such as amphibians, which are capable of tissue regeneration. Furthermore, mammalian foetuses through mid-gest...

    journal_title:Experimental dermatology

    pub_type: 杂志文章,评审

    doi:10.1111/exd.12457

    authors: Ud-Din S,Volk SW,Bayat A

    更新日期:2014-09-01 00:00:00

  • The antihistamines clemastine and desloratadine inhibit STAT3 and c-Myc activities and induce apoptosis in cutaneous T-cell lymphoma cell lines.

    abstract::Mycosis fungoides and its leukaemic counterpart Sézary syndrome are the most frequent cutaneous T-cell lymphomas (CTCL), and there is no cure for these diseases. We evaluated the effect of clinically approved antihistamines on the growth of CTCL cell lines. CTCL cell lines as well as blood lymphocytes from patients wi...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/exd.12086

    authors: Döbbeling U,Waeckerle-Men Y,Zabel F,Graf N,Kündig TM,Johansen P

    更新日期:2013-02-01 00:00:00

  • The Sox2: GFP+/- knock-in mouse model does not faithfully recapitulate Sox2 expression in skin.

    abstract::Hair follicle heterogeneity may be regulated by distinct dermal papillae (DP) that represent mesenchymal lineages, which can be defined by Sox2 expression. However, it was recently shown that GFP expression in the Sox2: GFP+/- mouse model occurs in the DPs of all hair follicle types, challenging the idea that hair fol...

    journal_title:Experimental dermatology

    pub_type: 信件

    doi:10.1111/exd.13396

    authors: Salz L,Driskell RR

    更新日期:2017-11-01 00:00:00

  • Divalent cations (Mg2+, Ca2+) differentially influence the beta 1 integrin-mediated migration of human fibroblasts and keratinocytes to different extracellular matrix proteins.

    abstract::Directed migration of keratinocytes and fibroblasts is a fundamental prerequisite in wound healing. Cation-dependent affinity changes of integrins are responsible for cell adhesion to and deadhesion from extracellular matrix proteins and have been implicated in driving cell migration. The specific requirements for div...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/j.1600-0625.1995.tb00236.x

    authors: Lange TS,Kirchberg J,Bielinsky AK,Leuker A,Bank I,Ruzicka T,Scharffetter-Kochanek K

    更新日期:1995-06-01 00:00:00

  • Tobacco smoke-induced skin pigmentation is mediated by the aryl hydrocarbon receptor.

    abstract::It is widely recognized that tobacco smoke causes skin pigmentation. No studies, however, have directly evaluated the mechanisms of the changes in smoker's skin pigmentation. In this study, when cultured with water-soluble tobacco smoke extract, the human epidermal melanocytes grew to a large size and produced more me...

    journal_title:Experimental dermatology

    pub_type: 信件

    doi:10.1111/exd.12170

    authors: Nakamura M,Ueda Y,Hayashi M,Kato H,Furuhashi T,Morita A

    更新日期:2013-08-01 00:00:00

  • Calcitonin gene-related peptide (CGRP) may award relative protection from interferon-γ-induced collapse of human hair follicle immune privilege.

    abstract::Interferon-γ (IFNγ)-induced collapse of hair follicle (HF) immune privilege (IP) is a key element in the pathogenesis of alopecia areata. In this pilot study, we investigated whether the immunosuppressive neuropeptide, calcitonin gene-related peptide (CGRP), can protect from and/or restore IFNγ-induced HF-IP collapse....

    journal_title:Experimental dermatology

    pub_type: 信件

    doi:10.1111/j.1600-0625.2011.01432.x

    authors: Kinori M,Bertolini M,Funk W,Samuelov L,Meyer KC,Emelianov VU,Hasse S,Paus R

    更新日期:2012-03-01 00:00:00

  • Immunoreactivity of corticotropin-releasing hormone, adrenocorticotropic hormone and alpha-melanocyte-stimulating hormone in alopecia areata.

    abstract::Psychological factors are believed to play a role in the pathogenesis of alopecia areata (AA), a frequently encountered hair disorder. In our study, statistically significant elevation of psychological stress was felt by AA patients prior hair loss compared with control, which was strongly believed contributory to hai...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/j.1600-0625.2006.00443.x

    authors: Kim HS,Cho DH,Kim HJ,Lee JY,Cho BK,Park HJ

    更新日期:2006-07-01 00:00:00

  • Effect of skin barrier competence on SLS and water-induced IL-1alpha expression.

    abstract::For screening of a potential irritant it is essential that an early marker for irritation should be chosen which could be detected before the physiological signs of irritation occur. Interleukin 1 alpha (IL-1alpha) is widely accepted as such a marker in both in vivo and in vitro test systems. In this study, we have de...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1034/j.1600-0625.2001.110304.x

    authors: Gibbs S,Vietsch H,Meier U,Ponec M

    更新日期:2002-06-01 00:00:00

  • The methylenetetrahydrofolate reductase 677C>T gene polymorphism is not associated with chronic plaque psoriasis.

    abstract:BACKGROUND:Methylenetetrahydrofolate reductase (MTHFR) is involved in the formation of methyl donors, which contribute to DNA methylation. DNA methylation is an essential epigenetic feature playing a critical role in gene regulation and cellular differentiation. In addition, MTHFR activity affects plasma homocysteine l...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/j.1600-0625.2008.00713.x

    authors: Weger W,Hofer A,Stanger O,Wolf P,El-Shabrawi Y,Renner W,Kerl H,Salmhofer W

    更新日期:2008-09-01 00:00:00

  • How realistic is cutaneous gene therapy?

    abstract::Recent progress with innovative, experimental gene therapy approaches in animals, and recent improvements in our understanding and manipulation of stem cells, gene expression and gene delivery systems, have raised plenty of hopes in essentially all branches of clinical medicine that hitherto untreatable or poorly mana...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/j.1600-0625.1999.tb00392.x

    authors: Hengge UR,Taichman LB,Kaur P,Rogers G,Jensen TG,Goldsmith LA,Rees JL,Christiano AM

    更新日期:1999-10-01 00:00:00

  • The role of calcitonin gene-related peptide in cutaneous immunosuppression induced by repeated subinflammatory ultraviolet irradiation exposure.

    abstract::Ultraviolet (UV) light is an effective treatment for skin disorders like psoriasis in which the cutaneous neurosensory system may have a pathogenic role. In this study, we examined the possibility that UV modulation of the cutaneous neurosensory system and calcitonin gene-related peptide (CGRP) may contribute to local...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/j.0906-6705.2004.00185.x

    authors: Legat FJ,Jaiani LT,Wolf P,Wang M,Lang R,Abraham T,Solomon AR,Armstrong CA,Glass JD,Ansel JC

    更新日期:2004-04-01 00:00:00

  • Commentary on the practical guide for the study of sebaceous glands.

    abstract::For many years, the function of the sebaceous gland (SG) was underestimated and suggested by Albert M. Kligman as a remnant of human development, a 'living fossil with a past but no future'. However, the last two decades of studies and the discovery of neuro-endocrine pathways in skin have determined the importance of...

    journal_title:Experimental dermatology

    pub_type: 评论,杂志文章

    doi:10.1111/exd.12221

    authors: Nejati R,Skobowiat C,Slominski AT

    更新日期:2013-10-01 00:00:00

  • Tumor-educated myeloid cells: impact the micro- and macroenvironment.

    abstract::Immune escape mechanisms of cancers include some of the mechanisms normally used for immune homeostasis, particular those preventing autoimmunity; one of these is the polarisation of myeloid cells. Thereby, tumors, i.e. the cancerous and stromal cells, also condition distant sites like spleen and bone marrow via solub...

    journal_title:Experimental dermatology

    pub_type: 评论,杂志文章

    doi:10.1111/exd.12241

    authors: Becker JC

    更新日期:2014-03-01 00:00:00

  • Culture of the human pilosebaceous unit, hair follicle and sebaceous gland.

    abstract::Terence Kealey first pioneered the isolation and organ maintenance of human eccrine and sebaceous glands in the early to mid-1980. This led to subsequent methods describing the isolation and culture of human hair follicles, the human pilosebaceous unit as well as the sebaceous duct. The importance of these models in t...

    journal_title:Experimental dermatology

    pub_type: 杂志文章,评审

    doi:10.1111/exd.13669

    authors: Philpott MP

    更新日期:2018-05-01 00:00:00

  • Leishmaniasis, contact hypersensitivity and graft-versus-host disease: understanding the role of dendritic cell subsets in balancing skin immunity and tolerance.

    abstract::Dendritic cells (DC) are key elements of the immune system. In peripheral tissues, they function as sentinels taking up and processing antigens. After migration to the draining lymph nodes, the DC either present antigenic peptides by themselves or transfer them to lymph node-resident DC. The skin is the primary interf...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/j.1600-0625.2010.01116.x

    authors: Kautz-Neu K,Meyer RG,Clausen BE,von Stebut E

    更新日期:2010-08-01 00:00:00

  • Electrophysiological characterization of human keratinocytes using the patch-clamp technique.

    abstract::The living, not-cornified part of the epidermis consists mainly of keratinocytes. The control mechanisms of proliferation and differentiation are only partly understood. Similarly, the influence of ionic channels of the cell membrane on the proliferation of keratinocytes remains unclear. Preliminary investigations poi...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1034/j.1600-0625.2000.009003219.x

    authors: Wohlrab D,Wohlrab J,Markwardt F

    更新日期:2000-06-01 00:00:00

  • E-FABP induces differentiation in normal human keratinocytes and modulates the differentiation process in psoriatic keratinocytes in vitro.

    abstract::Epidermal fatty acid-binding protein (E-FABP) is a lipid carrier, originally discovered in human epidermis. We show that E-FABP is almost exclusively expressed in postmitotic (PM) keratinocytes, corresponding to its localization in the highest suprabasal layers, while it is barely expressed in keratinocyte stem cells ...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/exd.12111

    authors: Dallaglio K,Marconi A,Truzzi F,Lotti R,Palazzo E,Petrachi T,Saltari A,Coppini M,Pincelli C

    更新日期:2013-04-01 00:00:00

  • Intercellular pathway through hyaluronic acid in UVB-induced inflammation.

    abstract::Ultraviolet B (UVB) radiation induces inflammation in the skin specifically at the site of exposure. We unexpectedly found that UVB-induced inflammation was not induced in gp91phox-depleted mice. To test whether gp91phox is directly involved in UVB-induced inflammation, neutrophil- and hyaluronic acid-depleted mice we...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/exd.12032

    authors: Hiramoto K,Kobayashi H,Yamate Y,Ishii M,Sato EF

    更新日期:2012-12-01 00:00:00

  • Serum amyloid A1 secreted from UV-irradiated keratinocytes induces matrix metalloproteinase-1 in fibroblasts through toll-like receptor 4.

    abstract::Ultraviolet (UV) irradiation on skin triggers photoageing-related phenotypes such as formation of wrinkles. UV ray upregulates matrix metalloproteinase-1 (MMP-1), which in turn degrades extracellular matrix proteins, mostly collagens. Serum amyloid A1 (SAA1) is an acute-phase protein of which plasma concentration incr...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/exd.12979

    authors: Han S,Jin SP,Oh JH,Seo EY,Park CH,Yoon HS,Lee DH,Chung JH

    更新日期:2016-07-01 00:00:00

  • Production of multiple cytokines by cultured human melanomas.

    abstract::We screened a panel of 8 primary and 21 metastatic melanoma cell lines for constitutive secretion of cytokines. Melanomas expressed bioactivity for TGF-beta (8/25 lines) and IFN (7/12), but not IL-2. Immunoassays detected IL-1 alpha (4/25), IL-1 beta (12/25), IL-6 (13/29), IL-8 (29/29), TGF-beta 2 (5/12) and GM-CSF (1...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/j.1600-0625.1993.tb00031.x

    authors: Bennicelli JL,Guerry D 4th

    更新日期:1993-08-01 00:00:00

  • Role of scratch-induced cutaneous prostaglandin D production on atopic-like scratching behaviour in mice.

    abstract::NC/Nga mice are known to develop scratching dermatitis akin to atopic dermatitis, under conventional (Conv), but not under the specific-pathogen-free (SPF) condition. In this study, we examined the effects of mechanical-scratching on the spontaneous scratching counts (sign of itching), in relation to the cutaneous pro...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/j.1600-0625.2006.00540.x

    authors: Takaoka A,Arai I,Sugimoto M,Futaki N,Sakurai T,Honma Y,Nakaike S

    更新日期:2007-04-01 00:00:00

  • Nerve growth factor increases the mitogenicity of certain growth factors for cultured human keratinocytes: a comparison with epidermal growth factor.

    abstract::Newborn foreskin and adult skin keratinocytes (KTs) were cultured in 24-well plates using keratinocyte basal medium (KBM) either alone or supplemented with epidermal growth factor (EGF) or nerve growth factor (NGF), plus one of the following: insulin (INS), insulin-like growth factors (IGF)-1 or -2, transforming growt...

    journal_title:Experimental dermatology

    pub_type: 杂志文章

    doi:10.1111/j.1600-0625.1994.tb00283.x

    authors: Wilkinson DI,Theeuwes MJ,Farber EM

    更新日期:1994-10-01 00:00:00