Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examined the thermal and metabolic responses of six men during exercise in water at critical temperature (Tcw, 31.2 +/- 0.5 degrees C), below Tcw (BTcw, 28.8 +/- 0.6 degrees C), at thermoneutrality (Ttn, 34 degrees C), and above Ttn (ATtn, 36 degrees C). At each water temperature (Tw) male volunteers wearing only swimming trunks completed four 1-h experiments while immersed up to the neck. During one experiment, subjects remained at rest (R), and the other three performed leg exercise (LE) at three different intensities (LE-1, 2 MET; LE-2, 3 MET; LE-3, 4 MET). In water warmer than Tcw, there was no difference in metabolic rate (M) during R. The M for each work load was independent of Tw. Esophageal temperature (Tes) remained unchanged during R in water of ATtn (36 degrees C). However, Tes significantly (P less than 0.05) declined over 1 h during R at Ttn (delta Tes = -0.39 degrees C), Tcw (delta Tes = -0.54 degrees C), and BTcw (delta Tes = -0.61 degrees C). All levels of underwater exercise elevated Tes and M compared with R at all Tw. In water colder than Tcw, the ratio of heat loss from limbs compared with the trunk became greater as LE intensity increased, indicating a preferential increase in heat loss from the limbs in cool water. Tissue insulation (Itissue) was lower during LE than at R and was inversely proportional to the increase in LE intensity. A linearly inverse relationship was established between Tw and M in maintaining thermal equilibrium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Water temperature and intensity of exercise in maintenance of thermal equilibrium. 321 41

We generally choose transhiatal esophagectomy (THE) for patients with high risk for postoperative complications and for carcinoma of the lower thoracic esophagus, even if the tumor is in the advanced stage. In order to define indications for THE in esophageal cancer patients, we investigated 40 THE cancer patients according to the expressions of EGF/EGFR, p53 and p21. In patients with stage I, II, III and IV tumors, 5-year survival rates were 66.7%, 28.6%, 30.0% and 11.4%, respectively. The sites of first recurrence were the lymph nodes (n = 10) and single organs (n = 10). Dissemination (n = 3) and local recurrence (n = 2) were also seen as a first recurrence. According to EGF/EGFR, 5-year survival rate was 69% and 14% in the low and high EGF/EGFR groups, respectively. According to p53 expression, 5-year survival was 60% and 30% in the negative and positive groups, respectively; according to p21 expression, 5-year survival was 71% and 0% in the negative and positive groups, respectively. Significant difference was seen in EGF/EGFR and p21 groups. These data support less invasive surgery for some patients even for esophageal cancer patients. THE is a less invasive surgery, that also implies fewer curative procedure. Our results also showed that THE alone will be the only curative procedure necessary for some patients. We can determine therapeutic procedures using these new factors, and thus avoid unnecessary excess surgical stress in esophageal cancer patients.
Dis Esophagus 1998 Oct
PMID:Clinical results of transhiatal esophagectomy for carcinoma of the lower thoracic esophagus according to biological markers. 1007 2

A distinctive type of multilayered epithelium (ME) has been described at the neo-squamocolumnar junction and within columnar mucosa in patients with Barrett's esophagus (BE). This epithelium has morphologic and ultrastructural features of both squamous and columnar epithelium. Multilayered epithelium may represent an early or intermediate stage of columnar metaplasia; therefore, we performed this study to determine the morphologic and biologic characteristics of this epithelium and to gain insight into its derivation. Esophageal mucosal biopsies containing ME from 17 patients with BE were evaluated morphologically, stained with a variety of mucin histochemical stains; and also immunostained with antibodies against cytokeratins (CK) 13 (squamous epithelium marker); 14 (basal squamous epithelium marker) 7, 8/18, 19, and 20 (columnar epithelium markers), MIB-1 (proliferation marker); villin (intestinal brush border protein); and TGFalpha, EGFR, pS2, and hSP (enteric proliferation/differentiation regulatory peptides). The results were compared with normal esophageal squamous epithelium, normal gastric cardia epithelium, specialized-type intestinal epithelium (BE), and esophageal mucosal and submucosal gland duct epithelium. Multilayered epithelium expressed a pattern of mucin production (neutral mucin, sialomucin, and sulfomucin in 88%, 100%, and 71% of cases, respectively) and cytokeratin expression (CK 13 and 19 in the basal "squamoid" cells, CK 7, 8/18, 19, and 20 in the superficial "columnar" cells) similar to that of columnar epithelium in BE, and showed a high capacity for cellular proliferation (Ki-67-positive in 88% of cases) and differentiation (TGFalpha, EGFR, pS2 and villin-positive in 100%, 100%, 93%, and 66% of cases, respectively). The mucosal gland duct epithelium showed a similar phenotypic pattern and, in one case, was seen to give rise to ME at the surface of the mucosa. These data provide evidence in support of the hypothesis that ME represents an early or intermediate stage in the development of esophageal columnar metaplasia (BE). The mucosal gland duct epithelium may contain progenitor cells that can give rise to ME.
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PMID:Phenotypic characteristics of a distinctive multilayered epithelium suggests that it is a precursor in the development of Barrett's esophagus. 1134 67

Gastrointestinal stromal tumors (GISTs) are rarely reported in the esophagus. The authors report a patient with an esophageal GIST, incidentally found after an echocardiogram. CT scan and endoscopic ultrasonography showed the tumor in the dependence of the muscularis propria of the esophageal wall. An Ivor-Lewis esophagectomy was performed. The tumor was well-circumscribed involving the submucosal and the muscular layers of the esophagus, measuring 13.5 x 8.5 x 7.6 cm, without involving the surgical margins. Histologically, the tumor consisted of spindle cells, with low mitotic index (2/50 HPF), that were immunoreactive for KIT (CD117) and CD34, consistent with GIST of high risk of aggressive behavior. No adjuvant therapy was given to the patient, who is alive and without evidence of disease 1 year after surgery. Since esophageal GISTs are rarely reported in the literature and usually have a poor prognosis, the diagnostic differentiation of these tumors from other more common mesenchymal neoplasms is essential, both for therapeutic and prognostic reasons.
Dis Esophagus 2005
PMID:Esophageal GIST: therapeutic implications of an uncommon presentation of a rare tumor. 1577 48

Epidermal growth factor receptor is over-expressed in several tumors and is the target for the tyrosine kinase inhibitor gefitinib. This receptor is also over-expressed in esophageal adenocarcinomas. In non-small cell lung cancer, specific somatic mutations residing in the epidermal growth factor receptor tyrosine kinase in the activation loop and the glycine-rich P-loop, are responsible for an enhanced sensitivity toward gefitinib. We analyzed exons 19 and 21 coding for the receptor tyrosine kinase of the epidermal growth factor gene in 105 samples of esophageal (Barrett's) adenocarcinoma by denaturing high-pressure liquid chromatography. We found only one silent mutation in exon 19 of adenine to guanine in codon 754 leading to a substitution of K to K, the rest of the sample being wild-type genotype. In conclusion, mutations within the tyrosine kinase domain of EGFR associated with sensitivity of non-small cell lung cancer patients to gefitinib are not present in esophageal (Barrett's) adenocarcinoma.
Dis Esophagus 2007
PMID:Lack of EGFR gene mutations in exons 19 and 21 in esophageal (Barrett's) adenocarcinomas. 1722 3

Current in vivo investigations of tumor angiogenesis mainly rely on the results obtained from engrafted models in mice. In the present study, we attempt to assess the potential of human tumor endothelium to form neovasculature in different engrafted tumor models. The tumor endothelial cells were isolated from human esophageal squamous cell carcinoma, and then identified by anti-VEGFR1/2 immunoreactions and tube formation assay. Esophageal and lung cancer cells were subcutaneously inoculated into nude mice with human esophageal cancer endothelial cells (HECECs), respectively. The human umbilical vein endothelial cells (HUVECs) were also co-inoculated into mice with esophageal cancer cells as a control. The engrafted tumor growth was significantly promoted by co-inoculation of HECECs in comparison with injection of esophageal tumor cells alone. Immunohistochemistry of anti-CD31 and anti-huCD31 was performed to detect the micro-vessels in the engrafted tumors which revealed that the HECECs formed humanized micro-vessels and significantly increased the micro-vessel density in engrafted tumors comparing with the tumors without HECECs. However, HUVEC cells could not enhance the esophageal tumor growth and the growth of lung tumors could not be increased by HECECs, either. Few humanized blood vessels were found in these two groups of xenografts. These results suggest that the specific interaction between HECECs and esophageal tumor cells contributes to the neovasculature construction and esophageal tumor growth in xenografts.
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PMID:Human esophageal cancer endothelial cells increase tumor growth by incorporating with mouse endothelium. 1727 90

Neoadjuvant chemotherapy may improve the outcome of esophageal cancer after esophagectomy, but is accompanied by considerable toxicity by collateral destruction of normal cells. Such side effects may be avoided by developing therapies that specifically target molecular characteristics of tumors. The aim of the present study was to determine the proportion of esophageal squamous cell carcinoma (ESCC) patients that could possibly benefit from (a combination of) currently available targeted therapies, by assessing the frequency of immunohistochemical expression of their target molecular markers in ESCC tissues. Sections from a validated tissue microarray comprising 108 ESCCs were immunohistochemically stained for Bcl-2, c-KIT, cyclo-oxygenase-2 (COX-2), cyclin D1, estrogen receptor (ER), epidermal growth factor receptor (EGFR), Her-2/neu, progesterone receptor (PR), and vascular endothelial growth factor (VEGF). VEGF, cyclin D1, EGFR, and COX-2 could be detected in 55, 42, 40, and 40%, respectively. Her-2/neu, Bcl-2, and c-KIT were detected in 12, 11, and 10% of the tumors, respectively. No nuclear expression of ER or PR was noticed. Concurrent expression of two markers was noticed in 28% of ESCCs, whereas 25% of ESCCs showed concurrent expression of three markers. The concurrent expression of two of the most frequently expressed markers (VEGF, cyclin D1, EGFR, and COX-2) ranged from 11 (COX-2 and EGFR) to 26% (cyclin D1 and VEGF). The expression of all of these four markers was seen in 5% of ESCCs. Promising targets for molecular therapy in ESCC appear to be COX-2, VEGF, EGFR, and cyclin D1, as they are frequently overexpressed. Phase II clinical studies on these molecular markers may therefore be warranted. The role for targeted therapy against ER, PR, Her-2/neu, c-KIT, or Bcl-2 in ESCC seems limited.
Dis Esophagus 2009
PMID:Targets for molecular therapy in esophageal squamous cell carcinoma: an immunohistochemical analysis. 1930 10

Sensitization of esophageal nociceptive afferents by inflammatory mediators plays an important role in esophageal inflammatory nociception. Our previous studies demonstrated that esophageal mast cell activation increases the excitability of esophageal nodose C-fibers. But the intracellular mechanism of this sensitization process is still less clear. We hypothesize that extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling pathway plays an important role in mast cell activation-induced sensitization of esophageal nodose C-fiber neurons. Mast cell activation and in vivo esophageal distension-induced phosphorylations of ERK1/2 were studied by immuno-staining and Western blot in esophageal nodose neurons. Extracellular recordings were performed from nodose neurons using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. Nerve excitabilities were compared by action potentials evoked by esophageal distensions before and after mast cell activations with/without pretreatment of mitogen-activated protein kinases (MAPK)/ERK kinase inhibitor U0126. The expressions of phospho-ERK1/2 (p-ERK1/2) in the same nodose ganglia were then studied by Western blot. Mast cell activation enhances in vivo esophageal distension-induced phosphorylation of ERK1/2 in nodose neurons. This can be prevented by pretreatment with mast cell stabilizer cromolyn. In ex vivo esophageal-vagal preparations, both mast cell activation and proteinase-activated receptor 2 (PAR2)-activating peptide perfusion increases esophageal distension-induced mechano-excitability of esophageal nodose C-fibers and phosphorylation of ERK1/2 in nodose neurons. Pretreatment with MAPK/ERK kinase inhibitor U0126 prevents these potentiation effects. Collectively, our data demonstrated that mast cell activation enhances esophageal distension-induced mechano-excitability and phosphorylation of ERK1/2 in esophageal nodose C-fiber neurons. This reveals a new intracellular pathway of esophageal peripheral sensitization and inflammatory nociception.
Dis Esophagus 2011 Apr
PMID:ERK1/2 signaling pathway in mast cell activation-induced sensitization of esophageal nodose C-fiber neurons. 2107 20

Activating mutations in Epidermal Growth Factor Receptor (EGFR) are common in lung adenocarcinoma of never smokers but are rare in other types of cancer. Here we have analysed mutations in exons 19 to 21 of EGFR and in exons 19 and 20 of the EGFR homolog HER2 in 54 cases of Esophageal Squamous Cell Carcinomas (ESCC) from patients recruited in Kashmir, India, a region of high incidence for this cancer. We report the detection of 3 mutations (6%) in the ATP-binding regulatory loops of the tyrosine kinase domain of EGFR (deletion 746-750, P753L, G719D). No mutation was found in HER2. This is the first report of activating EGFR mutations in ESCC, of the same type as those detected in lung adenocarcinoma of never-smokers. This suggests that a small proportion of ESCC patients in this high incidence area may benefit from treatment with EGFR tyrosine kinase inhibitors.
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PMID:Mutations in epidermal growth factor receptor gene in esophageal squamous cell carcinoma patients in kashmir- a high incidence area of India. 2147 85

We report a 3-year-old boy who initially presented with abdominal pain and was subsequently found to have an esophageal perforation. The child did not respond to conservative management, and subsequent lymphadenopathy led to a lymph node biopsy demonstrating an anaplastic lymphoma kinase (ALK)+ anaplastic large cell lymphoma. Esophageal perforation and thickening is most commonly seen in children with a history of esophageal intervention or foreign body/caustic ingestion. Esophageal involvement in children with non-Hodgkin lymphoma (NHL) has not, to our knowledge, been reported in the literature. This case illustrates an unusual presentation of pediatric NHL.
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PMID:Anaplastic large cell lymphoma of the esophagus in a pediatric patient. 2187 13


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