Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inflammatory bladder disorders such as interstitial cystitis (IC) deserve attention since a major problem of the disease is diagnosis. IC affects millions of women and is characterized by severe pain, increased frequency of micturition, and chronic inflammation. Characterizing the molecular fingerprint (gene profile) of IC will help elucidate the mechanisms involved and suggest further approaches for therapeutic intervention. Therefore, in the present study we used established animal models of cystitis to determine the time course of bladder inflammatory responses to antigen, Escherichia coli lipopolysaccharide (LPS), and substance P (SP) by morphological analysis and cDNA microarrays. The specific aim of the present study was to compare bladder inflammatory responses to antigen, LPS, and SP by morphological analysis and cDNA microarray profiling to determine whether bladder responses to inflammation elicit a specific universal gene expression response regardless of the stimulating agent. During acute bladder inflammation, there was a predominant infiltrate of polymorphonuclear neutrophils into the bladder. Time-course studies identified early, intermediate, and late genes that were commonly up-regulated by all three stimuli. These genes included: phosphodiesterase 1C, cAMP-dependent protein kinase, iNOS, beta-NGF, proenkephalin B and orphanin, corticotrophin-releasing factor (CRF) R, estrogen R, PAI2, and protease inhibitor 17, NFkB p105, c-fos, fos-B, basic transcription factors, and cytoskeleton and motility proteins. Another cluster indicated genes that were commonly down-regulated by all three stimuli and included HSF2, NF-kappa B p65, ICE, IGF-II and FGF-7, MMP2, MMP14, and presenilin 2. Furthermore, we determined gene profiles that identify the transition between acute and chronic inflammation. During chronic inflammation, the urinary bladder presented a predominance of monocyte/macrophage infiltrate and a concomitant increase in the expression of the following genes: 5-HT 1c, 5-HTR7, beta 2 adrenergic receptor, c-Fgr, collagen 10 alpha 1, mast cell factor, melanocyte-specific gene 2, neural cell adhesion molecule 2, potassium inwardly-rectifying channel, prostaglandin F receptor, and RXR-beta cis-11-retinoic acid receptor. We conclude that microarray analysis of genes expressed in the bladder during experimental inflammation may be predictive of outcome. Further characterization of the inflammation-induced gene expression profiles obtained here may identify novel biomarkers and shed light into the etiology of cystitis.
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PMID:Gene expression profiling of mouse bladder inflammatory responses to LPS, substance P, and antigen-stimulation. 1205 14

The present study was carried out in order to examine the molecular status of selected growth factor receptors (GFR) in urinary bladder lesions, recently described by our group as representing 'Chernobyl cystitis'. Fibroblast growth factor receptor 3 (FGFR3), epidermal growth factor receptor 1 (EGFR1), EGFR2neu (a member of the same family), p53 and Raf-1 serine/threonine kinase expression were evaluated immunohistochemically in urinary bladder biopsies from 22 men with benign prostate hyperplasia (group 1). For comparison, 16 men with benign prostate hyperplasia and five women with chronic cystitis living in non-radio-contaminated areas of the country were also investigated as controls (group 2). Additionally, 14 patients with dysplasia, carcinoma in situ (CIS) and primary urothelial carcinoma (UC) operated before the Chernobyl accident as well as 23 patients with UC living in the radio-contaminated areas were included as pre- and post-Chernobyl UC groups 1 and 2, respectively. Chronic proliferative atypical cystitis ('Chernobyl cystitis') was observed in group 1 patients. Foci of dysplasia and CIS were found in 22 (100%) and 19 (86%) of the 22 cases, respectively; moreover, two small UC were also detected. Elevated levels of FGFR3, EGFR2/neu, p53 and to a lesser extent EGFR1 and Raf-1 expression in the urothelial dysplasia and CIS were evident for patients of group 1. Statistically significant differences in immunohistochemical scores for FGFR3, EGFR1, p53 and Raf-1 were observed between groups 1 and 2 and between group 1 and the post-Chernobyl UC group 2, where a change in expression of EGFR2/neu was also noted. A significant decrease in FGFR3 expression in additional pre-Chernobyl UC group 1 with dysplasia, CIS and UC compared with group 1 Chernobyl cystitis cases was detected. Our findings suggest that FGFR and EGFR signaling pathways, associated with p53 and Raf-1 activation, may contribute to multistage urothelial carcinogenesis caused by irradiation, through autocrine or paracrine growth stimulation.
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PMID:Upregulation of fibroblast growth factor receptor 3 and epidermal growth factor receptors, in association with Raf-1, in urothelial dysplasia and carcinoma in situ after the Chernobyl accident. 1696 95

Interstitial cystitis (IC) is a syndrome of bladder hypersensitivity with symptoms of urgency, frequency, and chronic pelvic pain. Although no consensus has been reached on the underlying cause of IC, several pathophysiologic mechanisms, including epithelial dysfunction, mast cell activation, and neurogenic inflammation, have been proposed. Despite multiple different causes of urinary cystitis, the bladder's response to cystitis is limited and typical. Animal experiments have shown upregulation of proteinase-activated receptors, tryptase, beta-nerve growth factor, inducible nitric oxide synthase, nuclear transcription factor-kappaB, c-Fos, phosphodiesterase 1C, cyclic adenosine monophosphate (cAMP)-dependent protein kinase, and proenkephalin B. After the noxious stimulus has abated, downregulation of genes appears to follow. Distention of the bladder results in the release of adenosine triphosphate (ATP) from urothelial cells, which activates purinergic P2X3 receptors. Activation by ATP of P2X3-expressing afferents is a fundamental signaling factor in bladder sensation and appears to play a role in bladder reflexes. Fos proteins present in spinal cord neurons have been shown to be upregulated in animals that have undergone cyclophosphamide-induced chemical cystitis. These and other findings suggest that neural upregulation occurs both peripherally and centrally in subjects with chronic cystitis. It is unclear whether neural mechanisms and inflammation are the cause of IC or the result of other initiating events. Neural upregulation is known to play a role in the chronicity of pain, urgency, and frequency and represents an exciting area of research that may lead to additional treatments and a better understanding of IC.
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PMID:Neural upregulation in interstitial cystitis. 1746 76

Urinary bladder cancer is a common malignancy in Egypt, thus reliable methodologies are required for screening and early detection. In this study, we analyzed the gene expression of a Schistosoma hematobium specific microRNA "Sha-miR-71a" and mitogen-associated protein kinase-3 (MAPK-3) in the urine samples of 50 bladder cancer patients and 50 patients with benign bilharzial cystitis. Fifty control subjects were also tested. Indirect hemagglutination test (IHA) diagnosed 70% of studied cancer cases as bilharzial associated bladder cancer (BBC), while histopathological examination detected only 18%. Urinary Sha-miR-71a & MAPK-3 revealed enhanced expression in BBC (p-value = 0.001) compared to non-bilharzial bladder cancer (NBBC) cases. Patients with chronic bilharzial cystitis exhibited a significant increase in gene expression compared to those with acute infection (p-value = 0.001). Sha-miR-71a and MAPK-3 showed good sensitivity and specificity in the diagnosis of BBC when analyzed by the receiver operating characteristic (ROC) curve. They were also prognostic regarding malignancy grade. Both biomarkers showed a positive correlation. Our results revealed that IHA is a reliable test in the diagnosis of bilharziasis associated with bladder cancer, and that Sha-miR-71a and MAPK-3 provide non-invasive specific biomarkers to diagnose BBC, as well as a potential role in testing bilharzial patients for risk to develop cancer.
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PMID:Role of a schistosoma haematobium specific microRNA as a predictive and prognostic tool for bilharzial bladder cancer in Egypt. 3313 49