A Simple Clinical Application for Locating the Anterior Ethmoidal Artery Using the Anterior Ethmoidal Foramen and the Anterior Nasal Spine.

PURPOSE: The anatomy and variations of the anterior ethmoidal artery (AEA) are clinically relevant. The anterior ethmoidal foramen (AEF) can be used to locate the initial site of the AEA, and the anterior nasal spine (ANS) is a constant bony marker in the anterior nasal atrium. However, there is no relevant research on AEF and ANS targeting the AEA. Hence, this study aimed to accurately locate the AEA through AEF and ANS using computed tomography. METHODS: A total of 120 (240 sides) sinus computed tomography scans were retrospectively selected and studied. The AEA was classified into grades I, Ⅱ, and Ⅲ group based on the relationship between the AEA and the skull base. The distance between AEF and ANS and the angle between AEF-ANS and the axial plane were measured. RESULTS: The average distance from AEF to ANS was 58.26±3.64 mm, and the corresponding angle was 60.05±5.93 degrees. The AEF-ANS distances and angles were negatively correlated with age. Moreover, the distances from AEF to ANS were significantly increased in the grade Ⅲ group compared with the grade Ⅱ group. CONCLUSION: The measurements obtained in this study add anatomic knowledge that can serve as a better intraoperative localization method of the AEA, which can help surgeons avoid relative complications during endoscopic sinus surgery.

Annexin A3 Knockdown Suppresses Lung Adenocarcinoma.

Our previous study identified an elevated abundance of annexin A3 (Anxa3) as a novel prognostic biomarker of lung adenocarcinoma (LADC) through quantitative proteomics analysis. However, the biological functions of Anxa3 in LADC are not fully clear. In this study, in vitro and in vivo assays were performed to investigate the effects of Anxa3 downregulation on the growth, migration, invasion, metastasis, and signaling pathway activation of LADC cells. After Anxa3 downregulation, the growth of A549 and LTEP-a2 LADC cells was slowed and they showed decreased migration and invasion in vitro. Anxa3 knockdown significantly inhibited tumor formation by A549 cells in vivo; while many metastases were formed by control A549 cells, there were obvious reductions in the numbers of lung, liver, and brain metastases formed by Anxa3 knockdown in A549 cells. Furthermore, Anxa3 knockdown significantly decreased MMP-2 and N-cadherin expression and increased E-cadherin expression both in cell lines in vitro and in tumor nodules examined during in vivo tumorigenesis assays. Interestingly, Anxa3 downregulation reduced the phosphorylated levels of MEK and ERK. In summary, Anxa3 knockdown inhibited the growth, migration, invasion, and metastasis of LADC, decreased the activation of the MEK/ERK signaling pathway, and modulated the expression of MMP-2, E-cadherin, and N-cadherin.

TIPE2 Inhibits Lung Cancer Growth Attributing to Promotion of Apoptosis by Regulating Some Apoptotic Molecules Expression.

Recent studies found that TIPE2 was involved in cancer development. However, little is known about TIPE2 in lung cancer. Our study aims to clarify the role of TIPE2 in lung carcinogenesis. We examined the expression of TIPE2 in lung squamous cancer (LSC), small cell lung cancer and lung adenocarcinoma (AdC) tissues and found that TIPE2 expression was lost in small cell lung cancer, compared with adjacent non-tumor tissues. Overexpression of TIPE2 significantly inhibited the growth of lung cancer cell H446 in vitro and even suppressed tumor formation in vivo. Flow cytometry analysis found TIPE2 overexpression promoted apoptosis of H446. In TIPE2 over-expression cells, caspase-3, caspase-9, and Bax were significantly up-regulated while Bcl-2 was down-regulated. Moreover, coincident results were shown by immunohistochemistry in tumors from nude mice. TIPE2 inhibited the phosphorylation of Akt, while promoting the phosphorylation of P38, but had no effect on IκBα and ERK pathway. Taken together, TIPE2 promoted lung cancer cell apoptosis through affecting apoptosis-related molecules caspase-3, caspase-9, Bcl-2 and Bax, possibly via regulating P38 and Akt pathways, indicating that TIPE2 might be a novel marker for lung cancer diagnosis and therapy.

BRAF p.Val600Glu (V600E) somatic mutation is mainly associated with MSS phenotype in metastatic colorectal cancer.

BACKGROUND: Oncogenic activation of EGF-signalling pathway is central to the progression of colorectal cancer. The use of mutations of the KRAS codons 12 and 13 as a selection biomarker for anti-endothelial growth factor receptor (EGFR) monoclonal antibody treatment is at present the first major step towards individualised treatment for patients with metastatic colorectal cancer. The impact of BRAF V600E mutation is not well documented. PATIENTS AND METHODS: A total of 803 metastatic cancer samples from colorectal cancer patients were explored for KRAS exon 2 and BRAF exon 15 mutations. BRAF mutated samples were characterized for mismatch repair function. RESULTS: Overall, 344 tumours were mutated, with 34 of them involving BRAF mutations (8 of microsatellite instability type). No specificity was found according to gender, age at diagnosis and tumour localisation. CONCLUSION: A complete analysis of KRAS, BRAF and PIK3CA status may identify approximately 10-15% additional patients who are unlikely to respond an EGFR-targeted monoclonal antibody and who may benefit from prospective and specific new biomarker-driven studies.

Germline APC mutation spectrum derived from 863 genomic variations identified through a 15-year medical genetics service to French patients with FAP.

Heterozygous APC germline alteration is responsible for familial adenomatous polyposis, a colon cancer predisposition with almost complete penetrance. Point mutations generally lead to truncated proteins or no protein at all. They mainly involve exon 3 to codon 1700 (exon 15). The work presented here delineates precisely the APC mutation spectrum from 15 years of systematic molecular screening which identified 863 independent alterations in the French population.

Anti-DR5 mAb ameliorate adjuvant arthritis rats through inducing synovial cells apoptosis.

OBJECTIVE: Study the therapeutic effects and immunoregulatory mechanisms of anti-DR5 mAb on adjuvant arthritis (AA) rats. METHODS: AA rats induced by CFA, were treated with anti-DR5 mAb through mainline administration. Effect on the synovial membranes of the tissues was detected by H&E staining. Flow cytometry and MTT assay were used for detecting the induced apoptosis in an in vitro system and TUNEL assay was used for analysis in an in vivo system. The involvement of the apoptotic pathway was further proved by a caspase inhibition assay. RESULTS: Anti-DR5 mAb could induce synovial cell apoptosis in an in vitro system, which was related with the mRNA expression of DR5 on the cell surface. The mRNA expressions of c-myc and bcl-2 were decreased in synovial cells and those of p21, p53, and bax were increased. The protein expressions of caspase-8/3/9, RANKL, JNK2, and c-Jun were raised and that of bcl-2 was decreased. When the caspase inhibitor was added to the synovial cells treated with anti-DR5 mAb, it showed a dose-dependence inhibition effect, indicating that anti-DR5 mAb inducing apoptosis might be through the caspase pathway. CONCLUSION: This study shows that anti-DR5 mAb can ameliorate arthritic symptoms. The mechanisms of the treatment are related to the increase in synovial cell apoptosis by regulating the mRNA expression of DR5 and apoptosis-related genes, prolonging the duration of the cell cycle by modulation of the mRNA expression of cell cycle-related genes, and the protein expression of the molecules in the caspase pathway and RANKL, JNK2, and c-Jun.

Evaluation of monkey intraocular pressure by rebound tonometer.

PURPOSE: To evaluate the usefulness of the TonoVet rebound tonometer in measuring intraocular pressure (IOP) of monkeys. METHODS: The accuracy of the TonoVet rebound tonometer was determined in cannulated eyes of anesthetized rhesus monkeys where IOP was controlled by adjusting the height of a connected perfusate reservoir. To assess the applicability of the equipment through in vivo studies, the diurnal fluctuation of IOP and effects of IOP-lowering compounds were evaluated in monkeys. RESULTS: IOP readings generated by the TonoVet tonometer correlated very well with the actual pressure in the cannulated monkey eye. The linear correlation had a slope of 0.922+/-0.014 (mean+/-SEM, n=4), a y-intercept of 3.04+/-0.61, and a correlation coefficient of r(2)=0.97. Using this method, diurnal IOP fluctuation of the rhesus monkey was demonstrated. The tonometer was also able to detect IOP changes induced by pharmacologically active compounds. A single topical ocular instillation (15 microg) of the rho kinase inhibitor, H1152, produced a 5-6 mmHg reduction (p<0.001) in IOP, lasting at least 4 h. In addition, topical administration of Travatan, a prostaglandin agonist, induced a small transient IOP increase (1.1 mmHg versus vehicle control; p=0.26) at 2 h after treatment followed by a pressure reduction at 23 h (-2.4 mmHg; p<0.05). Multiple daily dosing with the drug produced a persistent IOP-lowering effect. Three consecutive days of Travatan treatment produced ocular hypotension of -2.0 to -2.2 mmHg (p<0.05) the following day. CONCLUSIONS: The rebound tonometer was easy to use and accurately measured IOP in the rhesus monkey eye.

H-1152 effects on intraocular pressure and trabecular meshwork morphology of rat eyes.

PURPOSE: The aim of this study was to elucidate the effects of the Rho-kinase inhibitor, H-1152, on cultured human trabecular meshwork (HTM) cells, TM morphology, and intraocular pressure (IOP) in rats. METHODS: Cultured HTM cells were treated with H-1152. Changes in cell morphology and the organization of the actin cytoskeleton and focal adhesions were evaluated by microscopy and immunofluorescence. H-1152 was administered topically to the eyes of conscious rats, and IOP was measured with a commercially available tonometer before and after treatment. The eyes were enucleated 1 h after treatment, fixed, and processed for morphologic analysis by light and electron microscopy. RESULTS: Exposure of the cultured HTM cells to 20 microM of H-1152 induced elongation and separation of cells, deterioration, and loss of actin stress fibers and focal adhesions within 2 h. Topical administration of H-1152 resulted in a significant decrease in IOP from 0.5 to 6 h, with the maximum IOP reduction of 28.1% at 1 h post-treatment (P < 0.001; n = 10). H-1152 caused an expansion of the intercellular spaces and loss of extracellular material in the juxtacanalicular region of the TM in rat eyes. CONCLUSIONS: The IOP-lowering effect of H-1152 in rat eyes is likely due to changes in TM-cell morphology, the actin cytoskeleton, and cellular adhesions in the conventional outflow pathway. H-1152 has potential as a new antiglaucoma medication.

p62 Expression in primary carcinomas of the digestive system.

AIM: To characterize p62 expression and define the relationship between p62 expression and cell proliferation in primary carcinomas of the digestive system. METHODS: p62 expression was characterized in surgically resected tumor specimens from 60 patients with primary carcinomas of the digestive tract (including 22 esophageal carcinomas, 17 gastric carcinomas, and 21 colorectal carcinomas) and 40 patients with hepatocellular carcinoma (HCC) by immunohistochemistry (IHC). The cell proliferation was determined by IHC of Ki-67 in 40 patients with HCC. RESULTS: Twenty-two cases of esophageal carcinoma were histopathologically diagnosed as squamous cell carcinoma. We combined the gastric and colorectal carcinomas based on the equivalent histology. The 38 tumors in the combined groups, consisted of 17 well-differentiated, eight moderately differentiated, nine poorly differentiated carcinomas, and four mucinous adenocarcinomas. According to the criteria of Edmondson and Steiner, 40 patients with HCC were graded (2 grade I, 17 grade II and 21 grade III). p62 expression in primary carcinomas of the gastrointestinal tract (60/60,100%) was higher than that (27/40, 67.5%) of HCC (P<0.01, chi(2) = 19.63). High expression levels of p62 were positively correlated with histological grades in gastric and colorectal carcinomas (P<0.0001) and inversely associated with those in HCC (P = 0.0322). No significant correlations were observed for esophageal carcinomas (P = 0.8246). p62 expression was also detected in the cytoplasm of morphologically normal columnar epithelial cells adjacent to the cancer foci of gastric and colorectal carcinomas. In 40 HCC specimens, the mean Ki-67 labeling index (LI) was (19.6+/-16.0)%. It was (28.3+/-18.73)% in 12 cases with high p62 expression (+++), (7.53+/-14.83)% in 13 cases without p62 expression(-). Patients with a high p62 expression showed a significantly higher level of Ki-67 staining than those without p62 expression (P<0.05, t = 2.069). CONCLUSION: p62 expression is common in carcinomas of the digestive system and higher in carcinomas of the gastrointestinal tract than in primary HCC. p62 is a cellular differentiation-related protein. Cancer cells with a high p62 expression exhibited highgrowth fractions in HCC.