Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P39060 (endostatin)
 2,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is considerable evidence to support an immunopathogenic basis of psoriasis. However, changes such as altered angiogenesis have also been implicated in the pathogenesis of psoriasis. AE-941 (Neovastat; Aeterna Laboratories, Quebec City Quebec, Canada) is a naturally occurring product currently in clinical investigation that blocks two main mechanisms of angiogenesis activation, namely, vascular endothelial growth factor and matrix metalloproteinase. We hypothesized that psoriasis could be modulated by inhibiting the neovascularization of psoriatic plaques. We conducted a randomized dose-comparison trial to evaluate the safety and potential therapeutic benefit of AE-941, administered orally to patients with psoriasis. Forty-nine patients with psoriasis were enrolled and assigned to receive AE-941 at 30, 60, 120, or 240 mL/d for 12 weeks. Patients were followed up for another 12-week period. Improvement in the Psoriasis Area and Severity Index (PASI) score was observed in 50%, 41.7%, and 30.8% of the patients receiving 240, 120, and 60 mL/d, respectively. No patients receiving a dosage 30 mL/d showed a PASI score improvement. A statistically significant improvement with increasing dose was observed for the PASI score, severity of itch, and the physician's global assessment. The most commonly reported nonserious drug-related adverse events affected the gastrointestinal system in 12 of 49 patients (primarily nausea, diarrhea, vomiting, flatulence, and constipation) and the skin and appendages in 4 of 49 patients (primarily acne and rash). This randomized phase I/II study provides evidence that the antiangiogenic agent AE-941 offers a new therapeutic approach to the management of psoriasis.
J Am Acad Dermatol 2002 Oct
PMID:Neovastat (AE-941), an inhibitor of angiogenesis: Randomized phase I/II clinical trial results in patients with plaque psoriasis. 1227 Dec 97

Imiquimod (imidazoquinoline 5%) is a topical immune response modifier agent that inhibits angiogenesis, the growth of new blood vessels. In addition to its stimulation of cell-mediated immunity, imiquimod's antiangiogenic activity contributes to its clinical efficacy by interfering with pathological neovascularization that promotes disease progression. The antiangiogenic mechanisms of imiquimod are due to its: 1) induction of cytokines that themselves inhibit angiogenesis (interferons, IL-10, IL-12); 2) local up-regulation of endogenous angiogenesis inhibitors (TIMP, TSP-1); 3) local down-regulation of pro-angiogenic factors (bFGF, MMP-9); and 4) promotion of endothelial cell apoptosis. This report discusses these mechanisms and the rationale for imiquimod's use as an antiangiogenic agent. Key principles of antiangiogenic therapy are presented to describe how imiquimod may be applied in a well-tolerated fashion to treat a broad range of angiogenesis-dependent dermatological conditions, including actinic keratosis (AK), basal cell carcinoma (BCC), squamous cell carcinoma (SCC), lentigo maligna, hemangiomas, Kaposi's sarcoma, pyogenic granuloma, and external genital warts.
J Drugs Dermatol
PMID:Imiquimod as an antiangiogenic agent. 1630 56

As the second most common skin malignancy, cutaneous squamous cell carcinoma (cSCC) is an increasing health concern, while its pathogenesis at molecular level remains largely unknown. We studied the expression and localisation of two homologous basement membrane (BM) collagens, types XV and XVIII, at different stages of cSCC. These collagens are involved in angiogenesis and tumorigenesis, but their role in cancer development is incompletely understood. Quantitative RT-PCR analysis revealed upregulation of collagen XVIII, but not collagen XV, in primary cSCC cells in comparison with normal human epidermal keratinocytes. In addition, the Ha-ras-transformed invasive cell line II-4 expressed high levels of collagen XVIII mRNA, indicating upregulation in the course of malignant transformation. Immunohistochemical analyses of a large human tissue microarray material showed that collagen XVIII is expressed by tumor cells from grade 1 onwards, while keratinocytes in normal skin and in premalignant lesions showed negative staining for it. Collagen XV appeared instead as deposits in the tumor stroma. Our findings in human cSCCs and in mouse cSCCs from the DMBA-TPA skin carcinogenesis model showed that collagen XVIII, but not collagen XV or the BM markers collagen IV or laminin, was selectively reduced in the tumor vasculature, and this decrease associated significantly with cancer progression. Our results demonstrate that collagens XV and XVIII are expressed in different sites of cSCC and may contribute in a distinct manner to processes related to cSCC tumorigenesis, identifying these collagens as potential biomarkers in the disease.
Exp Dermatol 2016 05
PMID:Collagens XV and XVIII show different expression and localisation in cutaneous squamous cell carcinoma: type XV appears in tumor stroma, while XVIII becomes upregulated in tumor cells and lost from microvessels. 2683 83

The concept of a biomarker was defined as "a characteristic marker that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention" by the National Institutes of Health Biomarkers Definitions Working group in 2001. Clinical features, disease progress, therapeutic response and prognosis are heterogeneous among patients with systemic sclerosis (SSc). Therefore, biomarkers that can predict these matters are required for the progress of clinical practice. At present, SSc-specific autoantibodies are the most useful biomarkers for diagnosis and predicting clinical features. Otherwise, biomarkers specific only for SSc have not been identified yet. The glycoprotein krebs von den Lungen-6, surfactant protein-D and CCL18 are promising serum biomarkers of SSc-related interstitial lung diseases. Serum/plasma levels of brain natriuretic peptide and serum N-terminal pro-brain natriuretic peptide have been used as biomarkers for SSc-related pulmonary arterial hypertension. Other potential serum/plasma biomarkers for fibrosis and vascular involvement of SSc are connective tissue growth factor, interleukin-6, CCL2, CXCL4, intercellular adhesion molecule (ICAM)-1, P-selectin, vascular endothelial growth factor, von Willebrand factor, endostatin, endoglin and endothelin-1. In our multicenter prospective studies of Japanese early SSc, serum ICAM-1 levels were predictive for subsequent respiratory dysfunction and serum levels of CXCL8 and P-selectin were predictive for subsequent physical disability. Further large, multicenter, prospective, longitudinal studies will be needed to identify and validate critical biomarkers of SSc.
J Dermatol 2016 Jan
PMID:Biomarkers in systemic sclerosis: Their potential to predict clinical courses. 2678 4