Beta‐catenin expression and mutation in adult and pediatric Wilms' tumorsSU, MIN‐CHENG; HUANG, WAN‐CHEN; LIEN, HUANG‐CHUN
doi: 10.1111/j.1600-0463.2008.00914.xpmid: 19024596
Wilms' tumor is the most common pediatric renal neoplasm, but its occurrence in adults is very rare. In contrast to pediatric Wilms' tumor (PWT), very little is known about the pathogenesis of adult Wilms' tumor (AWT). Despite there currently being no morphological difference between AWT and PWT, a cytogenetic study has suggested that the pathogenesis of AWT might be different from that of PWT. Although dysregulation of the Wnt pathway has been implicated in PWT, its role in AWT has never been investigated. To investigate the role of dysregulation of the Wnt pathway in AWT, tumor samples from 4 AWTs and 19 PWTs were surveyed for subcellular localization of β‐catenin by immunohistochemistry and potential mutation of the β‐catenin gene by sequencing. Nuclear translocation of β‐catenin was found in one out of four cases of AWT, but none of them carried mutation of the β‐catenin gene. By comparison, nuclear translocation for β‐catenin and mutation of the β‐catenin gene were present in 53% (10/19) and 15.8% (3/19) of PWTs, respectively. Of the three mutations identified, we found a novel mutation combining a silent mutation (TCT to TCC, Ser37Ser) and an in‐frame six‐base‐pair deletion (del GGTGCC, del Gly38Ala39). This report suggests that dysregulation of the Wnt pathway might also play a role in the pathogenesis of AWT.
Expression of NEDD‐1, a PTEN regulator, in gastric and colorectal carcinomasKIM, SUNG SOO; YOO, NAM JIN; JEONG, EUN GOO; KIM, MIN SUNG; LEE, SUG HYUNG
doi: 10.1111/j.1600-0463.2008.00999.xpmid: 19024597
Recent studies have disclosed that NEDD4‐1 regulates PTEN activity by ubiquitination. NEDD4‐1 negatively regulates PTEN in cytosol and acts as an oncogenic protein. By contrast, NEDD4‐1 promotes PTEN nuclear import and acts as a tumor suppressor. Despite the importance of NEDD4‐1 in PTEN regulation in cancer cells, expression of NEDD4‐1 protein in cancer tissues is unknown. The aim of this study was to analyze NEDD4‐1 expression in colorectal and gastric cancer tissues. We investigated NEDD4‐1 protein expression in 103 colorectal and 60 gastric carcinoma tissues by immunohistochemistry using a tissue microarray approach. In the cancers, expression of NEDD4‐1 was detected in 82 (80%) of the colorectal carcinomas and 45 (75%) of the gastric carcinomas in cytoplasm. By contrast, the normal mucosal cells of both stomach and colon showed no or very weak expression of NEDD4‐1. There was no significant association of NEDD4‐1 expression with clinicopathologic characteristics, including invasion, metastasis and stage. Our data indicate that NEDD4‐1 overexpression is a feature of both colorectal and gastric carcinomas. The increased expression of NEDD4‐1 in malignant gastric and colorectal cells compared to their normal epithelial cells suggests that NEDD4‐1 expression may play a role in colorectal and gastric cancer development.
Alloiococcus otitidis —otitis media pathogen or normal bacterial flora?TANO, KRISTER; VON ESSEN, ROBERT; ERIKSSON, P.‐O.; SJÖSTEDT, ANDERS
doi: 10.1111/j.1600-0463.2008.01003.xpmid: 19024598
During the last decade a new potential otitis media pathogen, Alloiococcus otitidis, has been studied. It is still not clear whether this bacterium really is a pathogen, although it has been found in a high percentage of middle ear effusions in children. The present study aimed to investigate the presence of A. otitidis in the nasopharynx and outer ear canals, and to develop a culture method that would make it possible to isolate A. otitidis from these locations. Nasopharyngeal samples (n=129) from children below 6 years were investigated by conventional culture on blood agar plates with 6% saline and rabbit antisera against A. otitidis, and by a PCR method. In the same way, we investigated 10 samples from vestibulum nasi of healthy persons, 68 samples from outer ear canals of patients with acute or chronic ear problems, and 24 samples from outer ear canals of healthy persons. In a rat model of acute otitis media, we instilled living A. otitidis into rat middle ears through the tympanic bulla and evaluated the outcome clinically by otomicroscopy at days 3, 6 and 14. Of the 129 nasopharyngeal cultures, 9 were positive for A. otitidis by PCR, but none by the culture method. Of the 68 samples from patients with running ears, 4 were positive for A. otitidis by PCR, but none by the culture method. Of the 24 healthy ear canals, 7 were positive for A. otitidis by PCR and 3 of them also by the culture method. No A. otitidis could be found from the vestibulum nasi. The rat experiment showed that the reactions in the middle ears were mild; we could not provoke a purulent acute otitis media in any of the rats. There was a 7% prevalence of A. otitidis in children below 6 years. The highest prevalence (29%) was found in outer ear canals of healthy persons, which strongly suggests that A. otitidis is part of the normal bacterial flora of the outer ear canal. The doubtful pathogenicity is also confirmed by the fact that—in the rat model—A. otitidis elicited only a mild response in the middle ear. It was possible to isolate A. otitidis using a blood agar plate with 6% saline.
Immunohistochemical expression of multidrug resistance proteins in mature T/NK‐cell lymphomasSAGLAM, ARZU; HAYRAN, MUTLU; UNER, AYSEGUL H.
doi: 10.1111/j.1600-0463.2008.00974.xpmid: 19024599
Multidrug resistance (MDR) is defined as resistance of tumor cells to a wide spectrum of structurally and functionally unrelated drugs. One of the most important mechanisms in mediating MDR is that involving cellular drug efflux transporters. Drug resistance is a common and formidable obstacle to therapy in mature T/NK‐cell lymphomas and the MDR phenotype is thought to be one of the contributing mechanisms. In this study we assessed the immunohistochemical expression of P‐gp (P‐glycoprotein), MRP‐1 (multidrug resistance associated protein 1), BCRP (breast cancer resistance protein) and LRP (lung resistance protein) in 45 mature T/NK‐cell lymphomas diagnosed at our hospital. We detected P‐gp expression in 31% (13/42), MRP‐1 expression in 74% (31/42), BCRP in 78% (32/ 41) and LRP in 59% (26/44) of the cases. These findings show that our T/NK‐cell lymphoma cases display high frequency of MDR protein expression.
Platelet deposition in rabbit common carotid arteries promoted by arterial stenosis and spasmJØRGENSEN, LEIF; STRAUME, BJØRN; MUSTARD, JAMES FRASER
doi: 10.1111/j.1600-0463.2008.01022.xpmid: 19024600
Coronary arteriograhy in patients with ischemic heart disease often shows spasm of the coronary arteries. The question is whether spasm is a triggering factor for thrombosis in a stenotic artery. If so, what are the mechanisms for this? A stenosing teflon ring was applied to the right common carotid artery of anesthetized rabbits and l‐nor‐epinephrine was dripped over the outer surface of both carotid arteries, causing spasm. In control animals an indifferent solution did not cause spasm. Nineteen rabbits were killed 30 min or 24 h after treatment. Microscopically, arteries with stenosis and spasm contained thrombi nearby the stenosis significantly more often than arteries in control animals. In another 14 rabbits, killed at 30 min, the number of platelets on the intimal surface away from the stenosis was quantified. In arteries with both stenosis and spasm the counts were significantly greater than in arteries with no treatment. The intimal surface in stenotic and spastic arteries showed assumed imprints of eddying flow and endothelial injury downstream and upstream of the stenosis. Spastic arteries showed increased folding of the internal elastic membrane, altered endothelial cells, and adhering platelets. Spasm in a rabbit artery with a preformed stenosis facilitates thrombosis probably by creating increased flow disturbances. Spasm may induce endothelial injury, causing adherence of platelets.
Dipeptidyl peptidase IV expression in cancer and stromal cells of human esophageal squamous cell carcinomas, adenocarcinomas and squamous cell carcinoma cell linesGOSCINSKI, MARIUSZ ADAM; SUO, ZHEN HE; NESLAND, JAHN MARTHIN; FLØRENES, VIVI ANN; GIERCKSKY, KARL‐ERIK
doi: 10.1111/j.1600-0463.2008.01029.xpmid: 19024603
Dipeptidyl peptidase IV (DPPIV) is a transmembrane serine protease which is involved in the process of tumor invasion and development of metastases in human cancers. The aim of this study was to investigate the expression of DPPIV in cancer and stromal cells of both esophageal adenocarcinoma and squamous cell carcinoma (SCC). Tissue material from 159 patients was analyzed using immunohistochemistry. Western blotting was performed on cell lines and fresh frozen tissue sections. Results were compared with clinicopathological features. Evaluation of the immunohistochemical findings revealed significant differences between DPPIV expression in carcinoma cells and stromal cells, depending on the histological tumor type. A significantly higher level of DPPIV was found in adenocarcinomas compared to SCCs while no DPPIV was detected in normal esophageal epithelium. Overexpression of DPPIV in patients with adenocarcinoma was additionally associated with distant metastases. Thus, differences of DPPIV level in esophageal carcinomas compared with normal epithelium showed that esophageal malignancies were associated with an increased amount of cell surface‐bound DPPIV. Radiotherapy in patients had no impact on DPPIV expression in analyzed tissue samples. There was no correlation between DPPIV expression in cancer or stromal cells and survival of the patients.