1,721,106 research outputs found
Remedies for pemphigus containing anti Fas Ligand antibodies
No full textDisclosure of the use of FasL antagonist, e.g. of humanized antibodies directed against human Fas Ligands (also named CD95L or Apo1L and hereinafter abbreviated as FasL) for the prevention and/or treatment of skin diseases associated with keratinocytes acantholysis, particularly for the prevention and/or treatment of pemphigu
Pin Cell
No full textPinCell is a biotech company founded in October 2008 as an academic spin-off of the University of Modena and Reggio Emilia by initiative of Prof. Carlo Pincelli and Dr. Alessandra Marconi.
The Mission is to research and develop novel molecules that will increase the therapeutic options for neoplastic and chronic inflammatory skin diseases.
The research and development process is focused on drug discovery, drug physico-chemical characterization, preclinical pharmacology and toxicology studies and early phase clinical trials on healthy volunteers (phase I)
PinCell directs its discoveries to other biotechnological companies or to pharmaceutical industries in need for novel ideas for drug development or looking for products at advanced stage of development requiring rapid commercial transfer
Apoptotic pathways in the pathogenesis of pemphigus: targets for new therapies
No full textPemphigus is a group of rare autoimmune blistering diseases of the skin in which autoantibodies to desmosome cadherins, desmogleins, induce loss of cell-cell adhesion (acantholysis). In addition to steric hindrance and activation of intracellular phosphorylation cascade signaling pathways, apoptosis has been suggested to contribute to the mechanism by which pathogenic IgG induces acantholysis. We review the literature examining the role of apoptosis in pemphigus. Current data recognize a central role of apoptosis in the mechanisms of blister induction. In particular, here we stress the key role of FasL in pemphigus, as it is able to first induce apoptosis, then acantholysis. Being pro-apoptotic molecules important in blister formation, they could represent new specific targets for pemphigus treatment
Keratinocyte Stem Cells: friends and foes
No full textSkin and its appendages provide a protective barrier against the assaults of the environment. To perform its role, epidermis undergoes an ongoing renewal through a balance of proliferation and differentiation/apoptosis called homeostasis. Keratinocyte stem cells reside in a special microenvironment called niche in basal epidermis, adult hair follicle and sebaceous glands. While a definite marker has yet to be detected, data raised part in humans and part in the mouse system, point to a critical role of stem and its progeny transit amplifying cells in epidermal homeostasis. Stem cells are protected from apoptosis and are long-resident in adult epidermis. This renders them more prone to be the origin of skin cancer. In this review, we will outline the main features of adult stem cells in mouse and humans and discuss their fate in relation to differentiation, apoptosis and cancer
Autocrine nerve growth factor in human keratinocytes
No full textBiologically active nerve growth factor (NGF) is synthesised and released by proliferating normal human keratinocytes. NGF up-regulates the expression of NGF mRNA in keratinocytes. Keratinocytes express both the low (p75)- and the high-affinity (TrkA) NGF-receptors, which are located in the basal layer of the epidermis. K252, a specific inhibitor of trk phosphorylation, blocks NGF-induced keratinocyte proliferation, in absence of exogenous NGF. Normal keratinocytes over-expressing TrkA proliferate better than control transfectants, while the NGF mimicking anti-Trk antibody induces an increased keratinocyte proliferation in Trk over-expressing cells as compared to mock transfected keratinocytes. In addition, NGF over-expressing keratinocytes proliferate better than mock transfected cells. K252, by blocking TrkA phosphorylation, induces apoptosis in normal keratinocytes, but not in keratinocytes over-expressing bcl-2. Further-more, NGF transfected keratinocytes are protected from UV-B-induced keratinocyte apoptosis, by maintaining constant levels of Bcl-2 and Bcl-x(L). Taken together these results support the concept of an autocrine survival system sustained by NGF and its high-affinity receptor in human keratinocytes. Because NGF and Trk levels are highly expressed in psoriasis, one could speculate that NGF autocrine system plays a role in the mechanisms associated with this and other hyperproliferative skin conditions, including cancer. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved
Keratinocyte Stem Cells: Biology and Clinical Applications
No full textHuman epidermis represents a large reservoir of stem cells that continue to self-renew throughout life. Stem cells are essential for skin regeneration and for repair after wounding. They allow long-term culture of keratinocytes that produce large sheets of epidermis to cover extensive burns, thus being lifesaving for these patients. Furthermore, stem cells can be expanded in culture, genetically modified to correct the gene deficiency in genetic skin diseases. This chapter will describe the most recent data on stem cell biology and the potential medical applications of these cells
Disruption of beta1 integrin induces keratinocyte stem cell anoikis through the extrinsic apoptotic pathway
No full textUltraviolet B-induced down-regulation of nerve growth factor and its high-affinity receptor (trk) mRNAs in human keratinocytes.
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