Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic neutrophilic leukaemia is a rare myeloproliferative disease characterised by splenomegaly, sustained neutrophilia, raised vitamin B12 level and absence of the Philadelphia chromosome. We report a 74-year-old man who presented first with Sweet's syndrome and subsequently leukocytosis. He had splenomegaly, a raised vitamin B12 level, serum uric acid and neutrophil alkaline phosphatase score. Cytogenetic study of the marrow was normal and peripheral blood for BCR-ABL gene transcript was not detectable. He subsequently passed away with bronchopneumonia.
 ...
PMID:Chronic neutrophilic leukaemia. 1734 75

Recently, a number of medications approved for nondermatologic use have proved useful against dermatologic diseases. This article reviews the dermatologic uses and effects of deferasirox, bortezomib, dasatinib, and cyclosporine eye drops. Deferasirox--an oral iron chelator--could be an effective treatment against porphyria cutanea tarda, hemochromatosis, and pathogens such as mucor that thrive in iron rich environments. Bortezomib, a proteasome inhibitor and multiple myeloma treatment, may be effective against nodular amyloid and has been effectively used against squamous cell carcinoma; although trials demonstrate it is ineffective against metastatic melanoma. Bortezomib has many cutaneous side effects including erythematous plaques or nodules, a generalized morbilliform erythema with ulcerations and fever, purpuric eruptions, leukocytoclastic vasculitis, Sweet's syndrome, and folliculitis. Dasatinib is a multi-targeted tyrosine kinase inhibitor active in vitro against most cell lines containing BCR-ABL mutations that confer resistance to imatinib. Dasatinib is likely to be effective against dermatofibroma sarcoma protuberans and cutaneous acute lymphoblastic leukemia, and has caused panniculitis. Cyclosporine 0.05% ocular emulsion (eye drops) are approved to treat dry eyes including dry eyes caused by collagen vascular disease. Cyclosporine eye drops might also have utility in treating eye pathology of ocular rosacea, atopic keratoconjunctivitis, graft versus host disease, herpes keratitis, chronic sarcoidosis of the conjunctiva, conjunctival manifestations of actinic prurigo, keratitis of keratitis-ichthyosis deafness (KID) syndrome, and lichen planus-related kerato-conjunctivitis. This article speculates that cyclosporine eye drops would also be useful for any disease causing ectropion or eclabion of the eye as well as toxic epidermal necrolysis-related eye pathology (in particular corneal scarring).
 ...
PMID:A review of deferasirox, bortezomib, dasatinib, and cyclosporine eye drops: possible uses and known side effects in cutaneous medicine. 1737 1

Capsiate, a nonpungent capsaicin analogue, and its dihydroderivative dihydrocapsiate are the major capsaicinoids of the nonpungent red pepper cultivar CH-19 Sweet. In this study, we report the biological actions and underlying molecular mechanisms of capsiate on angiogenesis and vascular permeability. In vitro, capsiate and dihydrocapsiate inhibited vascular endothelial growth factor (VEGF)-induced proliferation, chemotactic motility, and capillary-like tube formation of primary cultured human endothelial cells. They also inhibited sprouting of endothelial cells in the rat aorta and formation of new blood vessels in the mouse Matrigel plug assay in response to VEGF. Moreover, both compounds blocked VEGF-induced endothelial permeability and loss of vascular endothelial (VE)-cadherin-facilitated endothelial cell-cell junctions. Importantly, capsiate suppressed VEGF-induced activation of Src kinase and phosphorylation of its downstream substrates, such as p125(FAK) and VE-cadherin, without affecting autophosphorylation of the VEGF receptor KDR/Flk-1. In vitro kinase assay and molecular modeling studies revealed that capsiate inhibits Src kinase activity via its preferential docking to the ATP-binding site of Src kinase. Taken together, these results suggest that capsiate could be useful for blocking pathologic angiogenesis and vascular permeability caused by VEGF.
 ...
PMID:Capsiate, a nonpungent capsaicin-like compound, inhibits angiogenesis and vascular permeability via a direct inhibition of Src kinase activity. 1817 15

Sweet's syndrome is a rare skin condition associated with both drug treatment and a number of different disease processes including haematological malignancies, inflammatory conditions and HIV infection. In this case report, we present a patient with HIV, haemophilia and hepatitis C who presented to our team with significant thrombocytopaenia and Sweet's syndrome. We discuss the difficulties with diagnosis and management in the context of multiple co-morbidities and suggest that both hepatitis C and HIV may have been aetiologically involved by suppressing platelet production and also causing bone marrow-driven neutrophilic disease.
Int J STD AIDS 2012 Jun
PMID:Sweet's syndrome in a patient with haemophilia, HIV and hepatitis C infection. 2280 50

Neutrophilic dermatosis (ND) confined to postmastectomy lymphedema, localized Sweet syndrome, is a newly recognized disease. In this study, the authors describe a 44-year-old obese woman with chronic myelogenous leukemia in molecular remission on dasatinib therapy, who presented with a painful urticarial eruption limited to lipo-lymphedematous skin and accompanied by malaise, episodic fever, diarrhea, neutrophilia, and leukocytosis. Initially transient and migratory, the rash became fixed, papular, and vesicular and showed minimal response to corticosteroids. Biopsy demonstrated sparse perivascular and interstitial dermal neutrophilic infiltrates, without vasculitis or significant dermal edema. Aggregates of neutrophils were found within and surrounding lymphangiectases. Biopsy of a new onset papule 3 weeks later demonstrated papillary dermal edema, denser neutrophilic infiltrate, and vasculitis-like changes. These 2 histopathologic patterns of ND, early and late, resemble neutrophilic urticarial dermatitis (also known as neutrophilic dermatitis with systemic inflammation) and Sweet syndrome, respectively. Extensive workup did not reveal evidence of relapsed chronic myelogenous leukemia, infection, or a coexisting systemic inflammatory disease. Dasatinib was discontinued and the eruption gradually resolved over 2.5 months. Still in molecular remission (no detectable BCR-ABL gene fusion), dasatinib therapy was recommenced at 3-month follow-up. After 10 months, she complains of malaise and arthralgia, but no cutaneous symptoms. The evolution and slow resolution of this ND in lipo-lymphedematous skin implicate poor lymphatic clearance of factors, antigenic and/or toxic, involved in the pathogenesis of ND.
...
PMID:Neutrophilic Dermatosis Limited to Lipo-Lymphedematous Skin in a Morbidly Obese Woman on Dasatinib Therapy. 2682 66

Allogeneic hematopoietic stem cell transplantation (allo-SCT) has a curative potential for myelofibrosis (MF) patients; however, its association with a high therapy-related mortality (TRM) remains a big obstacle that needs to be overcome. Ruxolitinib (RUXO), a novel JAK1/2 inhibitor, can be used as a bridging therapy until allo-SCT can be performed to reduce TRM. We herein report a RUXO-treated MF patient who developed recurrent subcutaneous Sweet's disease (SSD) that was successfully treated by the administration of systemic glucocorticoids. We performed allo-SCT as previously scheduled, resulting in a good clinical course without deterioration of SSD. RUXO administration, as well as MF itself, might therefore sometimes cause this rare non-infectious event.
 ...
PMID:Recurrent Subcutaneous Sweet's Disease in a Myelofibrosis Patient Treated with Ruxolitinib before Allogeneic Stem Cell Transplantation. 2882 63

During the 2004 growing season in the Liaoning Province in China, where there was large population of whiteflies, several sweet potato (Ipomoea batatas) breeding lines showed leaf curl symptoms. A survey was conducted to determine the incidence of Sweet potato leaf curl virus (SPLCV) in China. Sixteen plants were collected and stem scions from those plants were graft inoculated to Ipomoea nil. Three weeks later, the indicator developed symptoms of leaf curling, interveinal chlorosis, and stunting. Total nucleic acid was extracted from young leaves of sweet potato and then evaluated using polymerase chain reaction (PCR). Primers, developed by Briddon and Markham (1) and used as universal primers for amplification of the geminivirus DNA fragment, were BM-V (5'-KSG GGT CGA CGT CAT CAA TGA CGT TRT AC-3') and BM-C (5'-AAR GAA TTC ATK GGG GCC CAR ARR GAC TGG C-3'). Amplified fragments with BM primers theoretically should have sizes almost equal to the full length of the DNA A component of the bipartite genome (2). Expected DNA fragments of 2.8 kb that contained the AV1, AV2, AC1, AC2, AC3, and AC4 open reading frames were obtained from symptomatic, but not from symptomless (uninfected) plants. The 2.8-kb fragments obtained by amplification were purified and cloned into the PMD18-T vector. Recombinant plasmids were then transformed into competent cells of Escherichia coli strain DH5(. The fragment was sequenced (GenBank Accession No. DQ512731), and nucleotide sequence of corresponding regions were compared with a published sequence of SPLCV available in GenBank (Accession No. AF104036). The AC4 and AC2 genes showed the highest (92%) and the lowest (83%) identity, respectively. This virus has been reported in the United States, Taiwan, Japan, and Peru. To our knowledge, this is the first report of the natural occurrence of SPLCV in China. References: (1) R. W. Briddon and P. G. Markham. Mol. Biotechnol. 1:202, 1994. (2) M. Onuki and K. Hanada. Ann. Phytopathol. Soc. Jpn. 64:116, 1998.
 ...
PMID:First Report of Sweet potato leaf curl virus in China. 3078 25