The aim was to examine the role of cyclooxygenase (COX)‐2‐mediated inflammation in the development of obese linked insulin resistance and fatty liver. The rats were fed separately regular diet (CONT), high‐fat diet (HFD) ad libitum, or energy restrictedly for 12 weeks. Rats fed HFD ad libitum were further divided into three subgroups co‐treated with vehicle (HFa), or a selective COX‐2 inhibitor celecoxib (HFa‐Cel) or mesulid (HFa‐Mes). Euglycemic hyperinsulinemic clamp (EHC) experiment was performed at the end of study. Another set of rats with similar grouping was further divided into those with a 4, 8, or 12‐week intervention period for hepatic sampling. Body weight was increased significantly and similarly in HFa, HFa‐Cel, and HFa‐Mes. Time‐dependent increases in plasma insulin, glucose, 8‐isoprostanes, leptin levels, homeostasis model assessment of insulin resistance (HOMA‐IR) and hepatic triglyceride contents shown in HFa were significantly reversed in HFa‐Cel and HFa‐Mes. During EHC period, the reduction in stimulation of whole body glucose uptake, suppression of hepatic glucose production and metabolic clearance rate of insulin shown in HFa were significantly reversed in HFa‐Cel and HFa‐Mes. The enhanced COX‐2 and tumor necrosis factor‐α (TNF‐α) but attenuated PPAR‐γ and C/EBP‐α mRNA expressions in epididymal fat shown in HFa were significantly reversed in HFa‐Cel and HFa‐Mes. The increases in average cell size of adipocytes and CD68 positive cells shown in HFa were also significantly reversed in HFa‐Cel and HFa‐Mes. Our findings suggest that COX‐2 activation in fat inflammation is important in the development of insulin resistance and fatty liver in high fat induced obese rats.

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Cortactin and fascin-1 are important factors in tumor progression. We tested the hypothesis that cortactin and fascin-1 expression correlates with clinicopathological parameters of gastric adenocarcinoma. Immunohistochemical analysis of cortactin and fascin-1 was done using tissue microarrays of 100 surgical specimens, including 20 well-differentiated, 20 moderately differentiated, and 60 poorly differentiated gastric adenocarcinomas. Among the 20 well-differentiated gastric adenocarcinomas, 15 cases (75%) showed negative or weak staining (1+); 5 cases (25%) had moderate (2+) or strong (3+) cortactin expression. Among the 60 poorly differentiated gastric adenocarcinomas, more than three-quarters of the cases (76.7%) had moderate or strong cortactin expression; 14 cases (23.3%) had weak staining. Of 20 well-differentiated gastric adenocarcinoma cases, 14 (70%) showed negative or weak staining of fascin-1, whereas nearly one-third (30%) had moderate or strong expression. Among the 60 poorly differentiated gastric adenocarcinomas, 32 (53.3%) exhibited moderate or strong fascin-1 expression; fewer than half of the cases showed negative or weak staining. Higher intensity of cortactin and fascin-1 staining correlated directly with more-advanced cancer stages (TNM) and inversely with survival rates. Our findings suggest the possibility that pharmacological inhibitors of cortactin and fascin-1 activity may slow down tumor progression and prolong survival time in patients with gastric adenocarcinomas.

Background: To report on an 11-year-old boy with a painless slow-growing temporal bulbar conjunctival mass of his left eye. Methods: A case report and review of the literature. Results: An 11-year-old boy presented with a painless slow-growing mass in the temporal bulbar conjunctiva of his left eye, which had been noted for 1 year. After ophthalmic and systemic evaluations, the clinical differential diagnosis at the time included amelanotic naevus, amelanotic melanoma, myxoma, fibrous histiocytoma, reactive lymphoid hyperplasia and lipoma. This lesion was excised under local anaesthesia. From the histopathological features, conjunctival myxoma was confirmed. After 12 months, the patient remained healthy, with no recurrence or metastasis of the conjunctival lesion or evidence of a systemic abnormality. Conclusion: We report this case to emphasize that conjunctival myxoma can appear as a well-circumscribed, translucent, yellow-pink conjunctival mass in teenage patients. Successful healing is usually achieved by complete surgical resection. Cardiac, endocrine, and family screening is required to reduce the risk of morbidity and mortality.

This study aimed to evaluate the relationship of fascin-1, matrix metalloproteinase (MMP)-2, MMP-9, cortactin, survivin, and epidermal growth factor receptor (EGFR) expression with clinicopathological parameters for the four most common ovarian surface epithelial carcinomas. Six biomarkers were investigated immunohistochemically using tissue microarrays of 185 specimens including 79 serous cystadenocarcinomas, 47 mucinous cystadenocarcinomas, 45 endometrioid adenocarcinomas, and 14 clear cell carcinomas. The four most common ovarian carcinomas showed significant expression of fascin-1, cortactin, survivin, and EGFR, but not of MMP-2 and MMP-9. In addition, higher immunostaining scores for fascin-1 in mucinous cystadenocarcinomas correlated with T stage, N stage, American Joint Committee on Cancer AJCC clinical stage, and a poorer survival rate; for cortactin in serous cystadenocarcinomas correlated with T stage; for cortactin in clear cell carcinomas correlated with T and clinical AJCC stages; and for survivin in clear cell carcinomas correlated with T stage and AJCC clinical stage. In addition, higher immunostaining scores for fascin-1, cortactin, and survivin correlated with poorer tumor differentiation in serous, mucinous, and endometrioid adenocarcinomas. Thus, the expression of fascin-1, cortactin, and survivin may be helpful in evaluating the aggressiveness of ovarian mucinous, serous, and clear cell adenocarcinoma. Additionally, the expression of fascin-1 may be an independent prognostic risk factor in mucinous cystadenocarcinoma.

EMMPRIN and fascin are important factors in tumor invasion and progression. We tested the hypothesis that expression of EMMPRIN and fascin correlate with clinicopathological parameters of renal cell carcinoma (RCC). Immunohistochemical analysis of EMMPRIN and fascin were performed in tissue microarrays of 100 surgical specimens, including 35 clear-cell RCC (CRCC), 21 clear-cell RCC with granular differentiation (GRCC), 12 chromophobe RCC (ChRCC), 8 papillary RCC (PRCC), 9 carcinoma of the collecting duct of Bellini (CDC), 10 clear-cell RCC with sarcomatoid differentiation (SRCC), and 6 metastatic RCC. Average immunoscores of EMMPRIN were 100.8 in CRCC, 195.2 in GRCC, 298.4 in ChRCC, 219.2 in PRCC, 186.1 in CDC, 226.9 in SRCC, and 151.7 in metastatic RCC. Among all included cases, average EMMPRIN immunoscores were 84.6 in grade I, 130.4 in grade II, 184.3 in grade III, and 223.5 in grade IV. Additionally, average immunostaining scores of fascin were 53.6 in CRCC, 289.3 in GRCC, 193.3 in ChRCC, 151.8 in PRCC, 181.3 in CDC, 275.4 in SRCC, and 131.7 in metastatic RCC. Average fascin immunoscores were 59.3 in grade I, 91.6 in grade II, 130.2 in grade III, and 194.7 in grade IV. Higher EMMPRIN and fascin immunoscores also correlated significantly with TNM stages and survival rates in RCC. Significant correlation was found between EMMPRIN and fascin expression. In conclusion, higher expression of EMMPRIN and fascin correlate significantly with histological grades, clinical stages, and survival rates of RCC.

Intracellular pH (pH(i)) exerts considerable influence on cardiac contractility and rhythm. Over the last few years, extensive progress has been made in understanding the system that controls pH(i) in animal cardiomyocytes. In addition to the housekeeping Na(+)-H(+) exchanger (NHE), the Na(+)-HCO(3)(-) symporter (NHS) has been demonstrated in animal cardiomyocytes as another acid extruder. However, whether the NHE and NHS functions exist in human atrial cardiomyocytes remains unclear. We therefore investigated the mechanism of pH(i) recovery from intracellular acidosis (induced by NH(4)Cl prepulse) using intracellular 2',7'-bis(2-carboxethyl)-5(6)-carboxy-fluorescein fluorescence in human atrial myocardium. In HEPES (nominally HCO(3)(-)-free) Tyrode solution, pH(i) recovery from induced intracellular acidosis could be blocked completely by 30 microM 3-methylsulfonyl-4-piperidinobenzoyl, guanidine hydrochloride (HOE 694), a specific NHE inhibitor, or by removing extracellular Na(+). In 3% CO(2)-HCO(3)(-) Tyrode solution, HOE 694 only slowed the pH(i) recovery, while addition of HOE 694 together with 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (an NHS inhibitor) or removal of extracellular Na(+) inhibited the acid extrusion entirely. Therefore, in the present study, we provided evidence that two acid extruders involved in acid extrusion in human atrial myocytes, one which is HCO(3)(-) independent and one which is HCO(3)(-) dependent, are mostly likely NHE and NHS, respectively. When we checked the percentage of contribution of these two carriers to pH(i) recovery following induced acidosis, we found that the activity of NHE increased steeply in the acid direction, while that of NHS did not change. Our present data indicate for the first time that two acid extruders, NHE and NHS, exist functionally and pH(i) dependently in human atrial cardiomyocytes.

The aim of this study was to test whether expression of EMMPRIN and fascin correlates with clinicopathologic parameters of pancreatobiliary adenocarcinoma. Immunohistochemical analysis of EMMPRIN and fascin was performed in 100 surgical specimens obtained from Chinese patients, including 18 well-differentiated, 62 moderately differentiated, and 20 poorly differentiated pancreatic and biliary adenocarcinomas. Neither EMMPRIN nor fascin was detectable in normal pancreatic and biliary glandular epithelia. However, EMMPRIN and fascin immunoreactivity was observed on the cell membrane and within the cytoplasm in pancreatobiliary adenocarcinomas. Higher immunostaining scores of EMMPRIN and fascin were strongly associated with advanced grades of pancreatobiliary adenocarcinomas (36.1 and 51.3 for grade I, 95.5 and 110.1 for grade II, and 133.7 and 165.8 for grade III). In addition, higher immunostaining scores of EMMPRIN and fascin were associated with advanced T stages (29.8 and 43.6 for T1, 86.3 and 93.2 for T2, 107.6 and 117.6 for T3, and 129.5 and 156.5 for T4). Higher EMMPRIN and fascin scores were associated with shorter survival times and more advanced M and N stages of pancreatiobiliary adenocarcinomas. A higher expression of EMMPRIN and fascin was found to correlate well with histologic grades and clinical stages of pancreatobiliary adenocarcinomas.