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Tumor Entity (tumor + entity)
Selected AbstractsIdentification of molecular targets associated with transformed diffuse large B cell lymphoma using highly purified tumor cells,AMERICAN JOURNAL OF HEMATOLOGY, Issue 12 2009Ulrika Andréasson Follicular lymphoma (FL) frequently transforms into the more aggressive diffuse large B cell lymphoma (DLBCL-tr), but no protein biomarkers have been identified for predictive or early diagnosis. Gene expression analyses have identified genes changing on transformation but have failed to be reproducible in different studies, reflecting the heterogeneity within the tumor tissue and between tumor samples. Gene expression analyses on Affymetrix Human Genome U133 Plus 2.0 arrays were performed, using flow cytometry sorted tumor cells derived from FL and transformed DLBCL. To identify molecular targets associated with the transformation, subsequent immunohistochemistry (IHC) analyses of the corresponding proteins were performed. Using highly purified cells, this study identified 163 genes, which were significantly deregulated during the transformation in a majority of cases. Among the upregulated transcripts, 13 genes were selected for validation using IHC, based on the availability of commercial antibodies, and galectin-3 and NEK2 proteins specifically identify DLBCL-tr, when compared with FL. We demonstrate that by purifying tumor cells through cell sorting, thereby reducing the heterogeneity due to infiltrating cells, it was possible to identify distinct differences between tumor entities rather than variations due to cellular composition. Galectin-3 and NEK2 both identified a subgroup of DLBCL-tr, and the function of these protein markers also suggests a biological role in the transformation process. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source] From the Background to the Spotlight: TASK Channels in Pathological ConditionsBRAIN PATHOLOGY, Issue 6 2010Stefan Bittner Abstract TWIK-related acid-sensitive potassium channels (TASK1,3) belong to the family of two-pore domain (K2P) potassium channels. Emerging knowledge about an involvement of TASK channels in cancer development, inflammation, ischemia and epilepsy puts the spotlight on a leading role of TASK channels under these conditions. TASK3 has been especially linked to cancer development. The pro-oncogenic potential of TASK3 could be shown in cell lines and in various tumor entities. Pathophysiological hallmarks in solid tumors (e.g. low pH and oxygen deprivation) regulate TASK3 channels. These conditions can also be found in (autoimmune) inflammation. Inhibition of TASK1,2,3 leads to a reduction of T cell effector function. It could be demonstrated that TASK1,/, mice are protected from experimental autoimmune inflammation while the same animals display increased infarct volumes after cerebral ischemia. Furthermore, TASK channels have both an anti-epileptic as well as a pro-epileptic potential. The relative contribution of these opposing influences depends on their cell type-specific expression and the conditions of the cellular environment. This indicates that TASK channels are per se neither protective nor detrimental but their functional impact depends on the "pathophysiological" scenario. Based on these findings TASK channels have evolved from "mere background" channels to key modulators in pathophysiological conditions. [source] Molecular cytogenetic characterization of proximal-type epithelioid sarcomaGENES, CHROMOSOMES AND CANCER, Issue 3 2004Elena Lualdi Proximal-type epithelioid sarcoma is a recently described soft-tissue tumor that is distinguished from conventional-type epithelioid sarcoma by a far more aggressive clinical course, frequent location in the proximal anatomic regions, and variable rhabdoid morphology. Because of their rarity and peculiar morphology, proximal-type epithelioid sarcomas frequently pose serious diagnostic dilemmas, being easily misdiagnosed as a variety of other malignant neoplasms. To date, the information available on the genetic alterations associated with this tumor entity has been confined to single conventional cytogenetic reports. In this article, we present the results of a conventional and molecular cytogenetic analysis of six proximal-type epithelioid sarcomas. Spectral karyotyping analysis of these cases deciphered the characteristics of several marker chromosomes and complex translocations, leading to the recognition of recurrent rearrangements. The most frequently involved chromosome arm was 22q, and the identification of two cases with a similar translocation, t(10;22), suggests a role for one or more genes on chromosome 22 in the pathogenesis of this tumor and provides an opportunity for finely mapping the translocation-associated breakpoints. Chromosome arm 8q gain was also a frequent event and correlated with gain of MYC gene copy number, as demonstrated by fluorescence in situ hybridization. A review of both cases reported in the literature and those presented in this study reinforced the involvement of chromosomes 8 and 22 and also indicated frequent rearrangements of chromosomes 7, 14, 18, and 20. © 2004 Wiley-Liss, Inc. [source] Histopathology of Pleomorphic Adenoma in the Parotid Gland: A Prospective Unselected Series of 100 Cases,THE LARYNGOSCOPE, Issue 12 2001Eberhard Stennert MD Abstract Objectives/Hypothesis Histopathological characteristics of pleomorphic adenomas, especially of capsular alterations such as thin capsule areas, capsule-free regions, capsule penetration, satellite nodules, and pseudopodia in the different subtypes, are described. Study Design Prospective unselected series of 100 consecutive cases from 1997 to 2000. Methods Light microscopic examination and semiquantitative analysis of the pleomorphic adenomas. Results Fifty-one (51%) pleomorphic adenomas were classified as myxoid (stroma-rich) type, 35 (35%) specimens as cellular type, and 14 (14%) as classic subtype. Ninety-seven percent of all tumors showed areas with thin (<20 ,m) capsule independent of the tumor subtype. Tumors of myxoid subtype showed the absolute greatest regions of a thin capsule. Especially, tumors of myxoid type (71%) often had a distinct focal absence of encapsulation with tumor merging into normal parotid gland tissue; 11% of the cellular subtype and 43% of the classic subtype presented capsule-free areas. Thirty-three percent of the myxoid pleomorphic adenomas, 23% of the cellular subtype, and 21% of the classic subtype had satellite nodules or pseudopodia. Conclusions Almost all pleomorphic adenomas have focally thin capsules. One-fourth of all pleomorphic adenomas contain abnormalities such as satellite nodules or pseudopodia. More than two-thirds of pleomorphic adenomas of the myxoid (stroma-rich) subtype and at least half of all tumors show a focal absence of the capsule. Therefore, enucleation or local dissection of the pleomorphic adenoma is not a sufficient surgical treatment of this special tumor entity. We recommend, depending on the location of the tumor, a lateral or total parotidectomy as the treatment of choice. [source] Target Gene Activation of the Wnt Signaling Pathway in Nuclear ,-Catenin Accumulating Cells of Adamantinomatous CraniopharyngiomasBRAIN PATHOLOGY, Issue 3 2009Annett Hölsken Abstract Activating ,-catenin (CTNNB1) mutations can be identified in the majority of adamantinomatous craniopharyngiomas (adaCP), suggesting an aberrant Wnt signaling pathway in this histopathologically peculiar tumor entity. However, there is no proven evidence that nuclear translocation of ,-catenin is associated with CTNNB1 mutations and target gene activation. We performed a laser-microdissection-based study comparing ,-catenin accumulating vs. non-accumulating tumor cells. Mutational analysis and gene expression profiling using real-time polymerase chain reaction were conducted in adamantinomatous and papillary tumor specimens. Target gene activation, that is, over-expression of Axin2 could be detected in adaCP, especially in tumor cells with nuclear ,-catenin accumulation. In addition, increased expression of BMP4 was identified in the accumulating cell population, which supports the hypothesis of an oral ectodermal origin. Interestingly, accumulating and non-accumulating tumor cell populations carried CTNNB1 mutations within exon 3. We extended the analysis, therefore, towards genetic regions encoding for membrane linkage and active/passive nuclear transport mechanisms (exon 4 and exon 8,13), but could not detect any alteration. This is the first report demonstrating an association between nuclear ,-catenin accumulation and target gene activation in adaCP. The results confirm the Wnt signaling pathway as molecular basis of the distinct and challenging clinical and morphological phenotype of adaCP. [source] | ||||||||||