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Article ; Online: Animal models of psoriasis.

Nickoloff, B J

2005 Volume 8, Issue 4, Page(s) 393–401

Abstract: Psoriasis is a common and chronic skin disorder under active investigation around the world. Despite this, determination of its genetic basis, role of the immune system in the disease pathophysiology and development of effective therapy, have been ... ...

Abstract	Psoriasis is a common and chronic skin disorder under active investigation around the world. Despite this, determination of its genetic basis, role of the immune system in the disease pathophysiology and development of effective therapy, have been hampered severely by the absence of any spontaneous psoriatic skin disease in animals. Furthermore, until recently, validated animal models designed to create psoriasis were unavailable to investigative skin biologists and clinical scientists. However, there is at least one animal model which has been established and validated; it uses human skin engrafted on to severe combined immunodeficient (SCID) mice. In addition, there are several other rodent models which do not involve transplantation technology that share some (but not all) features in common with psoriasis. This review will summarise these available animal models and critique their relevance with respect to illuminating the immunogenetic basis of psoriasis and their value in screening novel treatments in a preclinical setting.
Language	English
Publishing date	2005-06-07
Publishing country	England
Document type	Journal Article
ZDB-ID	1182884-5
ISSN	1744-7658 ; 0967-8298 ; 1354-3784
ISSN (online)	1744-7658
ISSN	0967-8298 ; 1354-3784
DOI	10.1517/13543784.8.4.393
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Article: The many molecular mysteries of melanoma.

Nickoloff, B J

Methods in molecular medicine

2001 Volume 61, Page(s) 3–14

Abstract: Melanoma of the skin is one of the most rapidly increasing malignancies in both young and old patients (1,2). Not only is the incidence increasing, but the number of annual deaths from melanoma is also on the rise worldwide (3). In the United States, ... ...

Abstract	Melanoma of the skin is one of the most rapidly increasing malignancies in both young and old patients (1,2). Not only is the incidence increasing, but the number of annual deaths from melanoma is also on the rise worldwide (3). In the United States, melanoma will be diagnosed in 43,000 new patients each year and be responsible for 7300 deaths (1 death every 72 min). The capacity of melanoma to develop in young patients is reflected by the rather alarming statistic that it has become one of the top causes of death in both men and women between the ages of 25 and 40 (3). Indeed, among Caucasian females, melanoma is the leading cause of death from malignancy between the ages of 25 and 29 (3). It is expected that by 2002, 1 in 70 Americans will develop melanoma during their lifetime (2). Also, melanoma is second only to adult leukemia as the leader in the number of potential years of life lost, which is significantly greater than for patients with cervical, breast, and colon malignancies (4). Despite the frequent presence of melanoma and major associated health problems around the globe, only recently have clinicians and laboratory-based researchers begun to unravel some of the molecular mysteries of melanoma (5,6). The purpose of Melanoma: Methods and Protocols, published as part of the Methods in Molecular Medicine™ series, is to provide an up-to-date review of the many advances that have taken place during the past several years involving the pathophysiology, diagnosis, genetic analysis, and treatment approaches for patients with melanoma (7).
Language	English
Publishing date	2001
Publishing country	United States
Document type	Journal Article
ISSN	1543-1894
ISSN	1543-1894
DOI	10.1385/1-59259-145-0:3
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Article: Creation of psoriatic plaques: the ultimate tumor suppressor pathway. A new model for an ancient T-cell-mediated skin disease. Viewpoint.

Nickoloff, B J

Journal of cutaneous pathology

2001 Volume 28, Issue 2, Page(s) 57–64

Abstract: From an oncological and immunological perspective, the T-cell-mediated induction of psoriatic plaques should be prone to malignant transformation as the phenotype of psoriatic plaques includes: chronic inflammation, epidermal hyperplasia, prolonged ... ...

Abstract	From an oncological and immunological perspective, the T-cell-mediated induction of psoriatic plaques should be prone to malignant transformation as the phenotype of psoriatic plaques includes: chronic inflammation, epidermal hyperplasia, prolonged survival and elevated telomerase levels in lesional keratinocytes, as well as angiogenesis, exposure to carcinogens and immunosuppressants. However, conversion of a psoriatic plaque to squamous cell carcinoma is exceedingly rare. This paper explores the possible molecular mechanism for the tumor suppressor pathway in psoriatic lesions, with an emphasis on a putative senescence-switch involving p16.
MeSH term(s)	Carcinoma, Squamous Cell/etiology ; Carcinoma, Squamous Cell/pathology ; Cell Transformation, Neoplastic ; Genes, Tumor Suppressor ; Humans ; Keratinocytes/pathology ; Models, Biological ; Precancerous Conditions ; Psoriasis/complications ; Psoriasis/genetics ; Psoriasis/immunology ; Psoriasis/pathology ; Skin Neoplasms/etiology ; Skin Neoplasms/pathology ; T-Lymphocytes/immunology ; T-Lymphocytes/pathology
Language	English
Publishing date	2001-02
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	187078-6
ISSN	1600-0560 ; 0303-6987
ISSN (online)	1600-0560
ISSN	0303-6987
DOI	10.1034/j.1600-0560.2001.280201.x
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Article: The search for pathogenic T cells and the genetic basis of psoriasis using a severe combined immunodeficient mouse model.

Nickoloff, B J

Cutis

2000 Volume 65, Issue 2, Page(s) 110–114

Abstract: The immunologic and genetic bases of psoriasis are under active investigation throughout the world. Rather than pursue the genetic linkage to psoriasis to discover the gene(s) responsible for causing the disease, we have focused on the cellular ... ...

Abstract	The immunologic and genetic bases of psoriasis are under active investigation throughout the world. Rather than pursue the genetic linkage to psoriasis to discover the gene(s) responsible for causing the disease, we have focused on the cellular immunology and basic biology using a novel animal model. We reasoned by identifying specific cellular and molecular abnormalities involved in the biologic responses that initiate lesion formation, that the genes involved in such a pathologic process would lead us to the correct causative DNA-based abnormality that determines disease susceptibility and inheritance. To pursue this line of inquiry, we utilized an animal model in which severe combined immunodeficient (SCID) mice were engrafted with symptomless skin (PN skin), and bona fide psoriatic plaques (PP skin) were created using specific pathogenic T cell subsets. This model can be used experimentally not only to study the mechanism by which PP skin is converted to PN skin, but also to create PP skin from PN skin. The clinical, histologic, immunologic, and pharmacologic validation of this SCID mouse model will be presented. This summary will also highlight the value of such a model, which has recently led to the discovery of previously overlooked types of immunocytes that are associated with induction of psoriatic lesions. Finally, a novel hypothesis linking the immunology and the genetics of psoriasis, based on findings using this animal model, will conclude this presentation.
MeSH term(s)	Animals ; Disease Models, Animal ; Mice ; Mice, SCID ; Psoriasis/genetics ; Psoriasis/immunology ; Psoriasis/pathology ; Skin/pathology ; Skin Transplantation ; T-Lymphocytes/immunology
Language	English
Publishing date	2000-02
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	391840-3
ISSN	0011-4162 ; 0151-9522
ISSN	0011-4162 ; 0151-9522
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Zs.B 1315: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 44: Show issues

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Article: Characterization of lymphocyte-dependent angiogenesis using a SCID mouse: human skin model of psoriasis.

Nickoloff, B J

The journal of investigative dermatology. Symposium proceedings

2000 Volume 5, Issue 1, Page(s) 67–73

Abstract: From a clinical perspective, angiogenesis is an important component of acute and chronic psoriatic skin lesions as they are erythematous and display a tendency to bleed after superficial removal of scale. By routine histology, numerous microscopic ... ...

Abstract	From a clinical perspective, angiogenesis is an important component of acute and chronic psoriatic skin lesions as they are erythematous and display a tendency to bleed after superficial removal of scale. By routine histology, numerous microscopic vascular abnormalities are also present. The structural expansion of capillaries and distinctive activated phenotype of lesional endothelial cells are believed not only to be clinical and pathologic hallmarks of the disease, but to play a central role in the pathogenesis of psoriatic plaques. Despite over 20 years of research by leading angiogenesis experts and numerous studies, many details regarding the cellular and molecular basis for angiogenesis in psoriasis remain unknown. In this review, 10 different sections are presented to update recent progress in this active field of investigative skin biology. Highlights of this review include the phenotypic characterization of endothelial cells in acute and chronic psoriatic plaques, and a review of a novel animal model of psoriasis using human skin engrafted onto severe combined immunodeficient mice followed by injection of activated immunocytes. This new experimental model represents a reproducible and pharmacologically validated method to trigger neovascularization and bona fide psoriatic plaque formation. In addition, the potential contribution of epidermal keratinocytes and dermal macrophages to the angiogenic tissue reaction is presented, and a series of questions are then posed that can be answered using the severe combined immunodeficient mouse model of psoriasis. Finally, a model is proposed integrating all available data into a coherent multistep reaction schema that includes active participation by multiple cell types including natural killer T cells, keratinocytes, macrophages, and microvascular endothelial cells.
MeSH term(s)	Animals ; Disease Models, Animal ; Humans ; Lymphocytes/physiology ; Mice ; Mice, SCID ; Neovascularization, Pathologic/immunology ; Neovascularization, Pathologic/pathology ; Psoriasis/immunology ; Psoriasis/pathology ; Psoriasis/physiopathology ; Skin/blood supply ; Skin/immunology ; Skin/pathology
Language	English
Publishing date	2000-12
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1338142-8
ISSN	1087-0024
ISSN	1087-0024
DOI	10.1046/j.1087-0024.2000.00006.x
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Zs.A 4510: Show issues

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Article: Skin innate immune system in psoriasis: friend or foe?

Nickoloff, B J

The Journal of clinical investigation

1999 Volume 104, Issue 9, Page(s) 1161–1164

MeSH term(s)	Animals ; Humans ; Immunity, Innate ; Keratinocytes/immunology ; Killer Cells, Natural/immunology ; Lymphocyte Subsets/immunology ; Mice ; Mice, Knockout ; Models, Immunological ; Phenotype ; Psoriasis/etiology ; Psoriasis/immunology ; Psoriasis/pathology ; Psoriasis/therapy ; Skin/immunology ; Skin/pathology
Language	English
Publishing date	1999-11
Publishing country	United States
Document type	Comment ; Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI8633
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Article: The immunologic and genetic basis of psoriasis.

Nickoloff, B J

Archives of dermatology

1999 Volume 135, Issue 9, Page(s) 1104–1110

MeSH term(s)	Animals ; Antigens, CD/immunology ; Cytokines/immunology ; Gene Expression Regulation/immunology ; Humans ; Immunophenotyping ; Keratinocytes/immunology ; Psoriasis/genetics ; Psoriasis/immunology ; T-Lymphocytes/immunology
Chemical Substances	Antigens, CD ; Cytokines
Language	English
Publishing date	1999-09
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	212139-6
ISSN	1538-3652 ; 0003-987X
ISSN (online)	1538-3652
ISSN	0003-987X
DOI	10.1001/archderm.135.9.1104
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Article: Immunologic reactions triggered during irritant contact dermatitis.

Nickoloff, B J

American journal of contact dermatitis : official journal of the American Contact Dermatitis Society

1998 Volume 9, Issue 2, Page(s) 107–110

Abstract: This article discusses a novel approach to the understanding of human skin barrier function with particular emphasis on the immunologic consequences of barrier perturbation. Clearly, the most important homeostatic function of the skin is to restrict the ... ...

Abstract	This article discusses a novel approach to the understanding of human skin barrier function with particular emphasis on the immunologic consequences of barrier perturbation. Clearly, the most important homeostatic function of the skin is to restrict the ebb and flow of water molecules to maintain a physiological balance with respect to hydration between the inside of the body and the external environment. The early investigators of barrier function initially focused on defining the biophysical properties of the stratum corneum and integrating the concepts of Singer and Nicholson1 into various models such as the brick and mortar concept by Elias2 and the domain mosaic model by Forslind.3 Rather than examining lipids, cholesterol, and free fatty acids in the stratum corneum, the authors have been interested in characterizing the types of specialized proteins termed cytokines that are intimately linked to the barrier structure and function of human and rodent skin.4 Cytokines are key mediators of inflammatory and immunologic reactions throughout the body; how these cytokines are modulated in response to changes in barrier function provides new insights that pass beyond the physical/mechanical protective nature of skin into the immunologic sphere of influence for barrier function and cutaneous homeostasis.
MeSH term(s)	Animals ; Cytokines/immunology ; Dermatitis, Irritant/immunology ; Humans ; Skin/immunology ; Skin Absorption
Chemical Substances	Cytokines
Language	English
Publishing date	1998-06
Publishing country	Canada
Document type	Journal Article
ZDB-ID	1069070-0
ISSN	1532-8163 ; 1046-199X
ISSN (online)	1532-8163
ISSN	1046-199X
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Article: Pathogenesis and immunointervention strategies for psoriasis. IBC's Inflammatory Skin Disorders. Washington, DC, USA. September 17-18, 1998.

Nickoloff, B J

Molecular medicine today

1998 Volume 4, Issue 12, Page(s) 512–513

MeSH term(s)	Animals ; Antibodies, Monoclonal/therapeutic use ; CD4-Positive T-Lymphocytes/immunology ; Clinical Trials as Topic ; Cytokines/immunology ; Cytokines/therapeutic use ; Humans ; Immunotherapy ; Intercellular Adhesion Molecule-1/immunology ; Lymphocyte Function-Associated Antigen-1/immunology ; Psoriasis/genetics ; Psoriasis/immunology ; Psoriasis/physiopathology ; Psoriasis/therapy
Chemical Substances	Antibodies, Monoclonal ; Cytokines ; Lymphocyte Function-Associated Antigen-1 ; Intercellular Adhesion Molecule-1 (126547-89-5)
Language	English
Publishing date	1998-12
Publishing country	England
Document type	Congress
ZDB-ID	1281487-8
ISSN	1878-4178 ; 1357-4310
ISSN (online)	1878-4178
ISSN	1357-4310
DOI	10.1016/s1357-4310(98)01377-x
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Article ; Online: 3-Bromopyruvate induces necrotic cell death in sensitive melanoma cell lines.

Qin, J-Z / Xin, H / Nickoloff, B J

Biochemical and biophysical research communications

2010 Volume 396, Issue 2, Page(s) 495–500

Abstract: Clinicians successfully utilize high uptake of radiolabeled glucose via PET scanning to localize metastases in melanoma patients. To take advantage of this altered metabolome, 3-bromopyruvate (BrPA) was used to overcome the notorious resistance of ... ...

Abstract	Clinicians successfully utilize high uptake of radiolabeled glucose via PET scanning to localize metastases in melanoma patients. To take advantage of this altered metabolome, 3-bromopyruvate (BrPA) was used to overcome the notorious resistance of melanoma to cell death. Using four melanoma cell lines, BrPA triggered caspase independent necrosis in two lines, whilst the other two lines were resistant to killing. Mechanistically, sensitive cells differed from resistant cells by; constitutively lower levels of glutathione, reduction of glutathione by BrPA only in sensitive cells; increased superoxide anion reactive oxygen species, loss of outer mitochondrial membrane permeability, and rapid ATP depletion. Sensitive cell killing was blocked by N-acetylcysteine or glutathione. When glutathione levels were reduced in resistant cell lines, they became sensitive to killing by BrPA. Taken together, these results identify a metabolic-based Achilles' heel in melanoma cells to be exploited by use of BrPA. Future pre-clinical and clinical trials are warranted to translate these results into improved patient care for individuals suffering from metastatic melanoma.
MeSH term(s)	Acetylcysteine/pharmacology ; Adenosine Triphosphate/metabolism ; Apoptosis ; Cell Line, Tumor ; Glutathione/metabolism ; Humans ; Melanoma/metabolism ; Melanoma/pathology ; Membrane Potential, Mitochondrial/drug effects ; Necrosis ; Pyruvates/pharmacology ; Skin Neoplasms/metabolism ; Skin Neoplasms/pathology ; Superoxides/metabolism
Chemical Substances	Pyruvates ; Superoxides (11062-77-4) ; bromopyruvate (63JMV04GRK) ; Adenosine Triphosphate (8L70Q75FXE) ; Glutathione (GAN16C9B8O) ; Acetylcysteine (WYQ7N0BPYC)
Language	English
Publishing date	2010-05-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2010.04.126
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