344 research outputs found

    Peroxisomes in intestinal and gallbladder epithelial cells of the stickleback, Gasterosteus aculeatus L. (Teleostei)

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    The occurrence of microbodies in the epithelial cells of the intestine and gallbladder of the stickleback, Gasterosteus aculeatus L., is described. In the intestine the organelles are predominantly located in the apical and perinuclear zone of the cells and may contain small crystalline cores. In gallbladder epithelial cells the microbodies are distributed randomly. The latter organdies are characterized by the presence of large crystalloids. Cytochemical and biochemical experiments show that catalase and D-amino acid oxidase are main matrix components of the microbodies in both the intestinal and gallbladder epithelia. These organelles therefore are considered peroxisomes. In addition, in intestinal mucosa but not in gallbladder epithelium a low activity of palmitoyl CoA oxidase was detected biochemically. Urate oxidase and L-α hydroxy acid oxidase activities could not be demonstrated.

    A study of Smad4, Smad6 and Smad7 in Surgically Resected Samples of Pancreatic Ductal Adenocarcinoma and Their Correlation with Clinicopathological Parameters and Patient Survival

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    <p>Abstract</p> <p>Background</p> <p>Smad4 is the common mediator of the tumor suppressive functions of TGF-beta. Smad6 and Smad7 are the antagonists of the TGF-beta pathway. This study investigates the differential protein expressions of Smad4, Smad6 and Smad7 in tumor as compared to normal tissue of pancreatic ductal adenocarcinoma (PDAC) and compares them with clinicopathological parameters and patient survival.</p> <p>Results</p> <p>There was a significant difference in protein expressions of Smad4 (p = 0.0001), Smad6 (p = 0.0015) and Smad7 (p = 0.0005) protein in tumor as compared to paired normal samples. Loss of Smad7 expression correlated significantly with tumor size (r = 0.421, p < 0.036) and margin status (r = 0.431; p < .032). Patients with moderate to high Smad4 protein expression had a better survival (median survival = 14.600 ± 2.112 months) than patients with absent or weak Smad4 protein expression (median survival = 7.150 ± 0.662). In addition, advanced disease stage correlated significantly with poor prognosis.</p> <p>Conclusion</p> <p>Loss of Smad4 significantly correlated with poor survival of PDAC patients. In the cases where Smad4 is expressed, Smad6 inhibition is possibly a novel mechanism for Smad4 inactivation. Smad7 has a role in pathobiology of PDAC. Further investigation in the roles of Smad6 and Smad7 would help in the identification of novel therapeutic targets for PDAC.</p

    Intraneural pseudocyst (so-called ganglion) in an unusual retroperitoneal periadnexal location?

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    A case of an unusual unilocular cystic lesion of diameter 7 cm located retroperitoneally in the pelvis in close connection to the right adnexa of a 61 year-old woman is presented. Macroscopically, the lesion had a smooth outer and inner surface and was filled with translucent fluid. Histological examination revealed a fibrous and hyalinized wall which lacked a specific lining. Numerous nerve bundles in the cyst wall constituted the most conspicuous element of its histology possibly with some contribution of perineurial and/or mesothelial components. The morphology and immunohistochemistry speak for an intraneural pseudocyst sometimes called intraneural ganglion cyst which is rare in this location

    The reg4 Gene, Amplified in the Early Stages of Pancreatic Cancer Development, Is a Promising Therapeutic Target

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    BACKGROUND: The aim of our work was to identify the genes specifically altered in pancreatic adenocarcinoma and especially those that are altered early in cancer development. METHODOLOGY/PRINCIPAL FINDINGS: Gene copy number was systematically assessed with an ultra-high resolution CGH oligonucleotide microarray in DNA from samples of pancreatic cancer. Several new cancer-associated variations were observed. In this work we focused on one of them, involving the reg4 gene. Gene copy number gain of the reg4 gene was confirmed by qPCR in 14 cancer samples. It was also found with increased copy number in most PanIN3 samples. The relationship betweena gain in reg4 gene copy number and cancer development was investigated on the human pancreatic cancer cell line Mia-PaCa2 xenografted under the skin of nude mice. When cells were transfected with a vector allowing reg4 expression, they generated tumors almost twice larger in size. In addition, these tumors were more resistant to gemcitabine treatment than control tumors. Interestingly, weekly intraperitoneal administration of a monoclonal antibody to reg4 halved the size of tumors generated by Mia-PaCa2 cells, suggesting that the antibody interfered with a paracrine/autocrine mechanism involving reg4 and stimulating cancer progression. The addition of gemcitabine resulted in further reduction, tumors becoming 5 times smaller than control. Exposure to reg4 antibody resulted in a significant decrease in intra-tumor levels of pAkt, Bcl-xL, Bcl-2, survivin and cyclin D1. CONCLUSIONS/SIGNIFICANCE: It was concluded that adjuvant therapies targeting reg4 could improve the standard treatment of pancreatic cancer with gemcitabine

    Whole-exome sequencing uncovers frequent GNAS mutations in intraductal papillary mucinous neoplasms of the pancreas

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    Intraductal papillary mucinous neoplasm (IPMN) is a common pancreatic cystic neoplasm that is often invasive and metastatic, resulting in a poor prognosis. Few molecular alterations unique to IPMN are known. We performed whole-exome sequencing for a primary IPMN tissue, which uncovered somatic mutations in KCNF1, DYNC1H1, PGCP, STAB1, PTPRM, PRPF8, RNASE3, SPHKAP, MLXIPL, VPS13C, PRCC, GNAS, KRAS, RBM10, RNF43, DOCK2, and CENPF. We further analyzed GNAS mutations in archival cases of 118 IPMNs and 32 pancreatic ductal adenocarcinomas (PDAs), which revealed that 48 (40.7%) of the 118 IPMNs but none of the 32 PDAs harbored GNAS mutations. G-protein alpha-subunit encoded by GNAS and its downstream targets, phosphorylated substrates of protein kinase A, were evidently expressed in IPMN; the latter was associated with neoplastic grade. These results indicate that GNAS mutations are common and specific for IPMN, and activation of G-protein signaling appears to play a pivotal role in IPMN

    MGMT promoter hypermethylation and K-RAS, PTEN and TP53 mutations in tamoxifen-exposed and non-exposed endometrial cancer cases

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    background: Tamoxifen has anti-oestrogenic and anti-tumour activity in the breast, but is oestrogenic and carcinogenic in the endometrium. It can induce experimental tumours by both hormonal and DNA-damaging mechanisms, but its carcinogenic mode of action in human endometrium remains unclear. methods: We investigated whether an epigenetic mechanism, involving promoter hypermethylation of the gene for the DNA repair enzyme MGMT (O6-methylguanine DNA methyltransferase), was associated with K-RAS, TP53 and PTEN mutations in endometrial tumours from women treated with tamoxifen (TAM, n=30) or unexposed to the drug (EC, n=38). results: There were significant (PA, occurred in small numbers in both groups. TP53 mutations were of mainly A>G, C>T and indel modifications in both groups, but more frequent in TAM cases. PTEN mutations dominated in EC tumours and were of the type that has large impact on protein function, such as indel or nonsense mutations. These observations alongside the mutational spectrum in PTEN suggest that the malignancies arise from different backgrounds, hence pointing to an effect of tamoxifen. Both groups displayed MGMT promoter hypermethylation. This coincided with mutations more frequently in the TAM (78%) than in the EC (50%) group, even though there were significantly (P<0.05) fewer mutations and methylations in TAM cases. conclusions: Although the difference in coincidence did not reach significance with the current sample size, the findings suggest that epigenetic processes may play a role in the way tamoxifen induces endometrial cancer
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