Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The benefits of estrogen replacement therapy in postmenopausal women include increased quality of life, relief from specific symptoms, and the prevention of osteoporosis, genitourinary atrophy, and cardiovascular diseases. Despite these advantages, this therapy has been reported to be associated with an increased frequency of endometrial hyperplasia and adenocarcinoma. In order to evaluate a possible relationship between the histological findings and stroma-derived growth regulators, 19 endometrial samples obtained from women undergoing both percutaneous (n = 11) and oral (n = 8) steroid replacement therapy were processed for histological and immunocytochemical evaluation of estrogen receptor (Er), progesterone receptor (Pr), and epidermal growth factor receptor (EGFr). Transdermal estradiol was given for 21 days and 10 mg medroxyprogesterone acetate (MAP) were added to the last 12 days; conjugated equine estrogens were given for 21 days and 10 mg MAP added to the last 12 days. Endometrial samples were obtained between days 17-18 of the sixth month of therapy. Proliferative and hyperplastic endometria showed immunoreactivity against Er, Pr, and EGFr. Atrophic endometria were always negative by immunocytochemistry. Our results suggest: 1) a relationship between histological findings and the receptor examined; 2) a crucial role for EGF in the regulation of endometrial proliferation.
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PMID:Steroid therapy and the endometrium: biological and clinical implications. 206 90

Forty-two patients with Stage III and IV advanced lung cancer received bronchial arterial infusion of Cyclophosphamide or Mitomycin in combination with Adriamycin and Cisplatin (CAP or MAP). Twenty-six patients were given radiotherapy too. Histologically, 16 had squamous cell carcinoma, 11 adenocarcinoma, 3 small cell anaplastic carcinoma and 1 un-classified cancer. Eleven were diagnosed by bronchial arterial radiography. The short-term results showed that complete response rate (CR) was 53.8% and partial response rate (PR) 38.5% in patients treated with combined chemotherapy and radiotherapy whereas in those treated with infusion chemotherapy, CR and PR were 0% and 81.3% respectively.
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PMID:[Bronchial arterial infusion chemotherapy with or without radiotherapy for advanced lung cancer]. 224 98

Hepatocyte growth factor (HGF) markedly induced the spreading, dissociation and scattering of Madin-Darby canine kidney epithelial cells (MDCK) and human stomach adenocarcinoma cells (TMK1). Scattering of MDCK and TMK1 cells was induced by 12-O-tetradecanoyl-phorbol-13-acetate (PMA) and epidermal growth factor (EGF), respectively. In all these agent-stimulated cells, rapid activation of Raf-1, MAP kinase/ERK kinase (MEK), 41/43 kDa MAP kinases and p90rsk was commonly observed. In contrast, PMA neither induced the scattering nor activation of all these kinases in TMK1 cells. Pretreatment of MDCK and TMK1 cells with 2-(2-amino-3-methoxyphenyl) choromone (AMPC), a specific inhibitor of MEK, selectively inhibited the HGF-, PMA- and EGF-stimulated activities of MEK, 41/43 kDa MAP kinases and p90rsk in a dose dependent manner. AMPC-pretreatment, however, did not affect HGF-, PMA- or EGF-induced activation of Raf-1, nor HGF-induced activation of phosphatidylinositol 3-kinase in these cells. Importantly, HGF-, PMA- and EGF-induced scattering of MDCK and TMK1 cells was inhibited at doses of AMPC similar to those that gave comparable levels of inhibition of the activities of MEK, 41/43 kDa MAP kinases and p90rsk. These results suggest that activation of the 41/43 kDa MAP kinase signaling pathway is required for the motility response of MDCK and TMK1 cells induced by agents such as HGF, PMA and EGF.
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PMID:Activation of the 41/43 kDa mitogen-activated protein kinase signaling pathway is required for hepatocyte growth factor-induced cell scattering. 967 14

RAGE (receptor for advanced glycation end products) is a multiligand cell surface molecule of the immunoglobulin superfamily. It was originally described as a receptor for protein adducts formed by glycoxidation (AGEs) that accumulate in diseases such as diabetes and renal failure. Performing RT-PCR and Western blot analysis we intended to determine RAGE expression in the human colon adenocarcinoma cell line Caco-2. Moreover, Caco-2 cells were incubated in the presence of AGEs. Since RAGE ligation triggers the p21(ras) signal transduction pathway the activation state of p44/42 (ERK1/2) MAP kinases was determined. Here we demonstrate for the first time that Caco-2 cells express RAGE and that administration of the food-derived casein-linked AGE N(epsilon)-(carboxymethyl)lysine (Cas-CML) results in Caco-2 p44/42 (ERK1/2) MAP kinase activation.
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PMID:RAGE expression and AGE-induced MAP kinase activation in Caco-2 cells. 1170 25

Recent studies suggest that sodium arsenite downregulates NF-kappaB activity by inhibiting phosphorylation and subsequent degradation of IkappaBalpha. Many effects of sodium arsenite are secondary to induction of heat shock proteins. The role of the heat shock response in arsenite-induced inhibition of NF-kappaB, however, is not known. We examined the involvement of the heat shock response in arsenite-induced inhibition of NF-kappaB activity in IL-1beta-stimulated Caco-2 cells, a human colorectal adenocarcinoma cell line with enterocytic properties. Treatment of the cells with IL-1beta resulted in increased IkappaB kinase activity, reduced levels of IkappaBalpha and increased NF-kappaB DNA binding activity. Sodium arsenite blocked all of these responses to IL-1beta without inducing changes in heat shock factor activity or heat shock protein levels. Results from additional experiments showed that the protective effect of sodium arsenite on IkappaBalpha was not influenced by the oxygen radical scavenger catalase or by inhibitors of the MAP-kinase signaling pathway. The present results suggest that sodium arsenite stabilizes IkappaBalpha and prevents NF-kappaB activation in IL-1beta-stimulated Caco-2 cells independent of the heat shock response. In addition, stabilization of IkappaBalpha by sodium arsenite does not require oxygen radical formation or activation of the MAP kinase signaling pathway.
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PMID:Arsenite stabilizes IkappaBalpha and prevents NF-kappaB activation in IL-1 beta-stimulated Caco-2 cells independent of the heat shock response. 1183 94

Five of six human small cell lung cancer (SCLC) cell lines changed morphologically into cells with neuronal-like processes on the extracellular matrix of human lung adenocarcinoma cell line PC-9 cells (PC-9 / ECM substrate). The features of the neuronal-like processes of these SCLC cell lines were examined immunocytochemically using monoclonal antibodies against beta-chains of tubulin and microtubule-associated protein-2 (MAP-2), which is somatodendritic MAP of neurons. It was observed that beta-chains of tubulin and MAP-2 were expressed along the neuronal-like processes of SCLC cell lines. These findings suggest that the beta-chains of tubulin and MAP-2 are expressed functionally in SCLC cell lines in association with the development of dendrite-like processes on PC-9 / ECM substrate.
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PMID:Immunocytochemical expression of microtubule-associated protein-2 (MAP-2) in small cell lung cancer cell lines with neuronal-like processes. 1207 19

Mitogen-activated protein kinases (MAP kinases) play a key role in the regulation of cell survival and death. Effects of Treponema denticola ATCC 35405 on ERK, p38 and JNK MAP kinases, and cell behavior was studied using non-keratinizing periodontal ligament epithelial cells (PLE) in vitro. Compared to Chinese hamster ovary cells, human cervix adenocarcinoma cells, human osteosacroma cells and human gingival fibroblasts, PLE cells were much more resistant to T. denticola-induced reduction in cell viability, assayed by tetrazolium and crystal violet assays. A low dose of 5 x 10(7) T. denticola cells/ml increased DNA synthesis ([3H]thymidine uptake) in PLE cells but at higher concentrations DNA synthesis was decreased. TUNEL staining analysis showed that about 50% of epithelial cells in onolayers died through apoptosis when exposed to a high dose of 10(11) T. denticola/ml for 24 h. Morphological light and electron microscopic analysis supported the idea that both apoptotic and necrotic cell death took place. Rounding, membrane damage, fragmentation and detachment were observed in selective cells of both mono- and multilayered PLE cultures challenged with T. denticola. Western blot analysis using MAP kinase phosphospecific antibodies showed that T. denticola strongly but transiently activated ERK1 and ERK2, signals mediating cell proliferation, and JNK and p38, kinases mediating apoptosis. While a specific inhibitor of the ERK MAP kinase pathway prevented the T. denticola stimulation of cell proliferation, inhibitor of p38 increased the cell numbers in T. denticola-treated cultures. The results suggest that T. denticola activates epithelial cell MAP kinase signal pathways controlling cell proliferation and cell survival. In addition, T. denticola exerts cytotoxic effects that appear to predominate at higher bacterial concentrations.
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PMID:Treponema denticola may stimulate both epithelial proliferation and apoptosis through MAP kinase signal pathways. 1247 39

Lung cancer continues to be the leading cause of cancer death in developed countries. With smoking the major etiological factor for lung cancer, there is a great need for the development of chemopreventive treatments that inhibit the progression of initiated cells and premalignant lesions into overt lung cancer in smokers who quit. Although the major focus of chemoprevention research has been on agents that inhibit the metabolic activation of genotoxic chemicals contained in tobacco products, some of these agents may additionally modulate growth-regulating signal transduction. In turn, the function of such signaling pathways is highly cell type-specific, with a given pathway inhibiting the growth of one cell type while stimulating the growth of others. The current experiment has tested the hypothesis that green tea and the methylxanthine theophylline contained in tea inhibit the progression of neuroendocrine lung carcinogenesis in hamsters with hyperoxic lung injury and initiated with the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) while promoting the development of Clara cell-derived pulmonary adenocarcinomas initiated by NNK in healthy hamsters. This hypothesis is based on published evidence that human small cell lung cancer as well as the neuroendocrine hamster tumors are regulated via autocrine signaling pathways that activate Raf-1 and the mitogen-activated (MAP) kinase pathway whereas human pulmonary adenocarcinomas of Clara cell lineage and the hamster model of this cancer type are regulated by a beta-adrenergic pathway involving the activation of cyclic adenosine 3',5'-monophosphate (cAMP) and the arachidonic acid (AA) cascade. In turn, it was hypothesized that theophylline would inhibit Raf-1-dependent tumor progression while promoting cAMP-dependent tumor progression due to its documented ability to inhibit the enzyme cAMP-phophodiesterase. The experimental design simulated chemoprevention in former smokers in that treatments with tea or theophylline started after completion of a 10-week tumor induction period with NNK. Our data show that green tea as well as theophylline significantly inhibited lung tumor multiplicity in the neuroendocrine cancer model whereas identical chemopreventive treatments significantly promoted the lung tumor multiplicity in the adenocarcinoma model. These findings indicate that green tea and theophylline as well as other chemopreventive agents that modulate signal transduction may have opposite effects on cancers of different histolopathology and cell lineage. At the current state of knowledge such chemopreventive treatments should only be used as adjuvant to cancer therapy of cancers that have been fully characterized at the pathology and molecular level.
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PMID:Neuroendocrine lung carcinogenesis in hamsters is inhibited by green tea or theophylline while the development of adenocarcinomas is promoted: implications for chemoprevention in smokers. 1519 29

We have shown that NADPH oxidase NOX5-S is overexpressed in Barrett's esophageal adenocarcinoma (EA) cells and may contribute to the progression from Barrett's esophagus (BE) to EA presumably by increasing cell proliferation and decreasing apoptosis (Fu X, Beer DG, Behar J, Wands J, Lambeth D, Cao W. J Biol Chem 281: 20368-20382, 2006). The mechanism(s) of NOX5-S overexpression in EA, however, is not fully understood. In SEG1 EA cells we found that acid treatment significantly increased platelet-activating factor (PAF) production, which in turn markedly increased NOX5-S expression and hydrogen peroxide (H(2)O(2)) production. Knockdown of NOX5-S by NOX5-S small interfering RNA (siRNA) blocked PAF-dependent H(2)O(2) production. PAF-dependent induction of NOX5-S expression and H(2)O(2) production were significantly decreased by the MAPK kinase 1 inhibitor PD-98059, by the cytosolic phospholipase A(2) (cPLA(2)) inhibitor AACOCF3, and by STAT5 downregulation with STAT5 siRNA. PAF significantly increased the phosphorylation of ERK1/2 MAPK, cPLA(2), and STAT5. Using inhibitors, we demonstrated that PAF-induced STAT5 phosphorylation depends on activation of ERK1/2 MAPK and cPLA(2), whereas PAF-induced cPLA(2) phosphorylation was associated with activation of ERK1/2 MAPK. Given that STAT5 bound to the c-sis-inducible element (TTCTGGTAA) of the NOX5-S promoter, overexpression of STAT5 significantly increased NOX5-S promoter activity. We conclude that acid-induced NOX5-S expression and H(2)O(2) production is mediated in part by production of PAF in SEG1 EA cells, and that PAF-induced increase in NOX5-S expression depends on sequential activation of ERK MAP kinases, cPLA(2), and STAT5 in these cells.
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PMID:STAT5 mediates PAF-induced NADPH oxidase NOX5-S expression in Barrett's esophageal adenocarcinoma cells. 1794 54

Neuropilin-1 (Np-1), a receptor for semaphorin 3A and vascular endothelial growth factor, is expressed at high levels in pancreatic ductal adenocarcinoma (PDAC). To assess the potential role of Np-1 in PDAC, COLO-357 pancreatic cancer cells, which express relatively low levels of Np-1, were stably transfected with the Np-1 cDNA. Np-1 overexpression was associated with enhanced cell invasiveness in response to hepatocyte growth factor (HGF), and this effect was abolished by small interfering RNA-mediated down-regulation of c-Met. Conversely, in PANC-1 pancreatic cancer cells, which express relatively high levels of Np-1, suppression of endogenous Np-1 completely abolished HGF-mediated cell invasion. To determine which pathways are involved in Np-1-mediated facilitation of c-Met-dependent cell invasiveness, the effects of HGF on signaling were examined next in sham-transfected and Np-1-overexpressing COLO-357 cells. HGF actions on c-Met tyrosine phosphorylation and p38 mitogen-activated protein kinase (MAPK) activation were increased in Np-1-overexpressing COLO-357 cells by comparison with HGF effects in sham-transfected cells. SB203580, an inhibitor of p38 MAPK, suppressed HGF-induced invasion in Np-1-overexpressing cells, whereas U0126, a MAP/extracellular signal-regulated kinase kinase inhibitor, was without effect. PP2, a Src inhibitor, and LY294002, a phosphatidylinositol 3-kinase inhibitor, also suppressed HGF-induced invasion in these cells. Immunoprecipitation studies revealed that Np-1 associated with c-Met, but not with epidermal growth factor receptor, family members. Confocal microscopy indicated that this association occurred on the plasma membrane and that HGF promoted the internalization of Np-1-c-Met complex, leading to its perinuclear localization. These findings indicate that Np-1 is required for efficient activation of c-Met-dependent pathways that promote cell invasiveness.
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PMID:Hepatocyte growth factor-mediated cell invasion in pancreatic cancer cells is dependent on neuropilin-1. 1797 73


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