Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.24.11 (CD10)
9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Barrett's mucosa consists of metaplastic columnar epithelium (specialized columnar epithelium) of the esophagus. Recently, "short-segment Barrett's esophagus (SSBE)" was proposed. In the present study, we examined immunohistochemical mucin expression and the Ki-67 labeling index (LI) of SSBE, in 5-15 mm lengths. All 27 SSBE cases showed gastric mucin (MUC5AC, HGM, MUC6). CD10 and MUC2, which were markers of intestinal phenotypes, were detected in 13 (48.1%) and 14 (51.9%) of the 27 SSBE cases. Ki-67 LI of SSBE positive cases for CD10 was 23.6 %, while that of SSBE negative cases for CD10 was 14.4 % (p < 0.05). SSBE cases were divided into two groups: one was gastric epithelium type with low Ki-67 LI, and the other was metaplastic epithelium with intestinal metaplasia and high Ki-67 LI. The latter group was suggested to be more important as a premalignant lesion of esophageal adenocarcinoma.
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PMID:Immunohistochemical mucin expression of short-segment Barrett's esophagus. 1471 30

An unusual case of synchronous gastric carcinomas occurred in a 28-year-old man with a family history of gastric disease. Two tumor foci were identified: a well-differentiated advanced carcinoma with the phenotypic properties of complete intestinal metaplasia and an early intestinal-type carcinoma. Histochemical and immunohistochemical stains to demonstrate complete intestinal metaplasia, ie, Alcian blue pH 2.5/periodic acid-Schiff, high iron diamine/Alcian blue pH 2.5, CD10, and MUC2, were all positive in the advanced adenocarcinoma. Of all markers used, only high iron diamine/Alcian blue pH 2.5 and Alcian blue pH 0.5 were positive in the early carcinoma. In these cases, mistakes frequently are made during examination of endoscopic biopsies. Fortunately, the advanced adenocarcinoma was low grade (the patient has shown no signs of disease at 6 years postsurgery). Histopathologic, histochemical, and immunohistochemical findings suggest that an extensive substrate of complete intestinal metaplasia (corpus) and of complete and incomplete intestinal metaplasia (antrum) can be associated with two independent tumors with different phenotypes.
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PMID:Advanced gastric carcinoma with a complete intestinal metaplasia phenotype associated with early intestinal-type carcinoma. 1473 79

In recent years there have been a plethora of publications regarding the value of immunohistochemical studies in diagnosis in gynecological pathology. In many instances, papers are published initially that suggest that a certain antibody or panel of antibodies is of value in the diagnosis of a particular neoplasm and in the distinction of this from mimics. However, this is usually quickly followed by other studies that somewhat contradict these findings. The aim of this review is to present a critical appraisal of the value of immunohistochemical studies in the diagnosis of uterine neoplasms with emphasis on the recent literature. It is stressed that immunohistochemistry is necessary in relatively few cases and a knowledge of the potential immunoreactivity of utilized antibodies is required. With regard to endometrial carcinoma, topics discussed in this review include antibodies of value in the distinction between type 1 and type 2 carcinoma, in the characterization of focal serous proliferations in endometrial polyps and non-polypoid endometrium, in the sometimes problematic distinction between an endometrial and an endocervical adenocarcinoma, and in the distinction between a uterine and ovarian serous carcinoma. The value of CD10 as a proposed marker of mesonephric adenocarcinoma is also discussed. With regard to uterine mesenchymal neoplasms, a critical appraisal of the value of relatively new antibodies, including CD10 and h-caldesmon, in distinguishing between a smooth muscle and an endometrial stromal neoplasm is discussed as is the immunophenotype of two rare uterine mesenchymal neoplasms, uterine tumor resembling ovarian sex cord tumor (UTROSCT) and perivascular epithelioid cell tumor (PEComa).
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PMID:A critical appraisal of the value of immunohistochemistry in diagnosis of uterine neoplasms. 1509 30

Epithelium of the gallbladder and biliary tract is exposed to high concentrations of potentially harmful exogenous and endogenous compounds excreted into primary bile. As the ATP-dependent efflux pump ABCG2 can prevent cellular accumulation of anticancer drugs, estrogen sulfate, xenobiotics, porphyrins, and sterols, its expression in the biliary tract might mediate protection by hindering their penetration. We therefore investigated the expression and subcellular distribution of ABCG2 in normal and malignant human gallbladder. After demonstrating ABCG2 expression in gallbladder epithelium by RT-PCR and Western blotting, we analyzed the subcellular localization of ABCG2 by indirect immunofluorescence in gallbladder adenocarcinoma specimens, and compared it to that in cholelithiasis, and normal gallbladder samples (n = 54). In control, cholelithiasis, and well-differentiated tumor samples (grade 1, T1-3), ABCG2 is present at the luminal membrane of epithelial cells, which was proven by colocalization of apical-bound TRITC-labeled lectin (wheat germ agglutinin). In poorly differentiated gallbladder adenocarcinomas, intracellular ABCG2, in addition to luminal ABCG2 immunoreactivity, was found in 13/21 carcinoma samples (grade 2 and 3, T2-4, P < 0.01). In 3/11 of grade 3 tumors, ABCG2 was present in the cytoplasmatic compartment only (P < 0.01). In proliferating bile ducts of cholangiocarcinomas, ABCG2 showed an analogous staining pattern with presence in cytosolic compartments. However, the apical marker enzyme neutral endopeptidase remained on the membrane in all samples. To study whether phosphatidylinositol 3-kinase (PI3K) signaling might be necessary for ABCG2 membrane insertion, we treated freshly isolated human gallbladder epithelial cells with the PI3K inhibitor wortmannin. As assessed by indirect immunofluorescence, this maneuver redistributes ABCG2 to intracellular compartments. In conclusion, our data suggest a protective role for ABCG2 in well-differentiated gallbladder epithelial cells. Cytoplasmatic accumulation of ABCG2 in poorly differentiated carcinomas might coincide with malfunctioning of PI3K-signaling pathways during tumor progression.
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PMID:Subcellular localization of the ABCG2 transporter in normal and malignant human gallbladder epithelium. 1514 67

We present a new antibody-directed enzyme prodrug therapy strategy (ADEPT) based on a post-proline cleaving endopeptidase and prodrugs, in which cytotoxic moieties are linked to a proline-containing peptide. Human prolyl endopeptidase was expressed in Escherichia coli and purified to homogeneity. The enzyme was active in buffer and in human serum but was rapidly thermally inactivated by incubation at 37 degrees C, thus preventing applications in vivo. While prolyl endopeptidase display on filamentous phage abolished viral infectivity and prevented directed evolution strategies based on phage display, we robotically screened 10752 individual colonies of mutant enzymes using a fluorogenic assay to improve enzyme stability. A single amino acid mutation (Glu289 --> Gly) improved protein stability, resulting in a half-life of 16 h at 37 degrees C in phosphate buffer. Two prodrugs were synthesized, in which an N-protected glycine-proline dipeptide was covalently coupled to doxorubicin and melphalan. (Benzyloxycarbonyl)glycylprolylmelphalan, but not the more sterically hindered doxorubicin prodrug, could be efficiently activated by prolyl endopeptidase [specific activity = 813.3 nmol min(-1) (mg of enzyme)(-1) at 25 degrees C]. The melphalan prodrug was essentially nontoxic to CHO, F9 teratocarcinoma, MCF7 breast adenocarcinoma, and p3U1 mouse myeloma cells up to millimolar concentrations, while prodrug incubation with the engineered prolyl endopeptidase mutant led to a cell killing profile superimposable to the one of melphalan. The prolyl endopeptidase mutant was then chemically coupled to the human antibody L19, specific to the EDB domain of fibronectin, a marker of angiogenesis. The resulting immunoconjugate retains antigen binding and enzymatic activity, thus opening the way to anticancer ADEPT applications.
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PMID:Engineering a thermostable human prolyl endopeptidase for antibody-directed enzyme prodrug therapy. 1514 13

We present a unique carcinoma of the pancreas with predominantly clear cell morphology (>95% clear cells). Mucicarmine stain revealed abundant intraluminal and intracytoplasmic mucin. Immunohistochemically, the cells were positive for the epithelial markers cytokeratin 7 and CAM 5.2, and were focally positive for cytokeratin 20. These cells also expressed monoclonal carcinoembryonic antigen. Stains for the neuroendocrine markers synaptophysin and chromogranin were negative, as were stains for vimentin, p53, HMB-45, and CD10. An additional outstanding feature was the presence of dense intraluminal and intracytoplasmic hyaline globules, which were immunohistochemically positive for alpha1-antitrypsin. Sequencing of the K-ras oncogene revealed a point mutation in codon 12, providing molecular evidence of ductal origin. In the proper morphologic context supported by immunohistochemistry, clear cell carcinoma can be regarded as a rare variant of ductal adenocarcinoma.
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PMID:Clear cell ductal adenocarcinoma of pancreas: a case report and review of the literature. 1516 26

We report the fine-needle aspiration (FNA) cytology findings of endometrioid adenofibroma arising in the ovary of a 60-year-old woman who presented with vaginal bleeding. Imaging studies revealed a large pelvic mass, which was sampled by computed tomography-guided FNA and core biopsy. The FNA yielded cellular smears composed of bland endometrioid cells and fragments of ovarian-type stroma. The core biopsy showed a biphasic process comprising bland endometrioid glands in a spindle-cell stroma. Immunohistochemical studies performed on the core showed the stroma to be CD10-negative and smooth muscle actin-positive. Subsequent resection of the tumor confirmed the diagnosis and revealed an adenocarcinoma arising in the tumor that was not sampled by FNA. To our knowledge, the cytologic features of ovarian endometrioid adenofibroma have not been previously described.
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PMID:Fine-needle aspiration cytology of endometrioid adenofibroma of the ovary. 1523 63

In the literature, sufficient attention has not been paid to the precise subcellular localization of immunohistochemical signals, the knowledge of which is essential for proper interpretation of immunostains and distinction of genuine staining from biotin-associated or other nonspecific stainings. The subcellular localization of the signals can in fact be easily deduced from the known biologic or ultrastructural characteristics of the antigens. Extracellular antigens obviously are located in the extracellular compartment. Cellular antigens fall into 3 major groups: membranous, nuclear, and cytoplasmic. Membranous antigens include cell adhesion molecules (such as E-cadherin, N-CAM), cell surface/transmembrane receptors and proteins (such as tyrosine kinase receptors, most leukocyte antigens, CD10, CEA), and molecules linking surface molecules to cytoskeleton (such as beta-catenin, dystrophin). Nuclear antigens include cell cycle-associated proteins (such as cyclins, p16, Ki-67), nuclear enzymes (such as TdT), transcription factors (such as TTF-1, CDX-2, myogenin, PAX-5), tumor suppressor gene products (such as p53, p63, WT1, Rb), steroid hormone receptors (such as ER, PR), calcium-binding proteins (such as S-100 protein, calretinin), and some viral proteins (such as CMV, herpes). Cytoplasmic antigens can take up a granular pattern due to localization in organelles, granules, or secretory vesicles (such as chromogranin, hormones, lysozyme, HMB-45), fibrillary pattern attributable to the filamentous nature of the molecules (intermediate filaments and microfilaments), or diffuse or patchy pattern due to localization in the cytosol or large vesicles (such as myoglobin, albumin, thyroglobulin). Aberrant localization of the molecules, when present, can provide important insight into disease processes and aid in their diagnosis, such as loss of membranous E-cadherin expression in lobular breast carcinoma, aberrant nuclear localization of beta-catenin in colorectal adenocarcinoma, pattern of ALK staining in anaplastic large cell lymphoma correlating with the different types of chromosomal translocations, presence of additional cytoplasmic CD10 staining in the enterocytes indicative of microvillous inclusion disease, and "reversed" staining for EMA in micropapillary mammary carcinoma.
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PMID:Subcellular localization of immunohistochemical signals: knowledge of the ultrastructural or biologic features of the antigens helps predict the signal localization and proper interpretation of immunostains. 1530 32

A case of an epithelioid variant of pleomorphic liposarcoma (PL) arising in the back of a 72-year old male is presented. The lesion was a well-circumscribed but unencapsulated, yellowish white mass measuring 11 x 10 x 9 cm in the subcutis and muscle. Histologically, the tumor consisted of three elements; an epithelioid cell element occupying about 50%, a lipogenic and mixed lipogenic and epithelioid cell element occupying 40%, and a malignant fibrous histiocytoma-like element. The lipogenic area was composed of uni- and multivacuolated pleomorphic lipoblasts. Immunohistochemically, the tumor was positive for vimentin, epithelial membrane antigen, and CD10. It was negative for desmin, alpha-smooth muscle actin, muscle actin, S-100 protein, and cytokeratins 8 and 18. The epithelioid variant of PL should be differentiated from metastatic renal cell carcinoma and adrenal cortical adenocarcinoma.
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PMID:Epithelioid variant of pleomorphic liposarcoma: report of a case. 1546 2

Cluster designation (CD) antigens are cell surface markers that can be used to identify constituent cell populations of an organ. We have previously determined the CD phenotype of normal prostate parenchymal cells and are now extending this analysis to prostate cancer. Since expression of CD antigens is associated with cellular differentiation, cancer cells may differ from their normal counterpart in their CD profile. Compared with luminal secretory cells, prostate adenocarcinoma cells are frequently negative for CD10 and CD13, express increased levels of the cell activation molecule CD24, and decreased levels of the apoptosis-associated multifunctional enzyme CD38. Expression of CD57, CD63, CD75s, CD107a, CD107b, CD164, and CD166 by cancer cells is similar to that of secretory cells. Prostate basal epithelial cells do not express the CD antigens characteristic of prostate secretory cells; and the basal cell CD markers, CD29, CD44, CD49b, CD49f, CD104, and nerve growth factor receptor (NGFR) are not expressed by cancer cells. The preferential expression of secretory cell-associated CD markers by prostate cancer cells suggests a closer lineage relationship between cancer cells and secretory cells than basal cells. Although the above cancer CD phenotype was the most frequently seen, some prostate cancers contained populations of CD10- and/or CD13-positive cells, and CD57-negative cells. Furthermore, the cancer phenotype of tumor metastasis is different. Despite its low frequency in primary tumors, CD10 is expressed by virtually all of the nodal metastases of prostate cancer. In addition, stromal fibromuscular cells associated with primary prostate cancer differ from stromal cells in benign prostate tissue by an increased level of expression of the cell activation molecule, CD90. In summary, our data show that the CD marker expression profile of prostate cancer cells most closely resembles that of secretory prostate epithelial cells and that some prostate cancers consist of heterogeneous cell populations as distinguished by CD-marker expression profiles.
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PMID:Heterogeneity in primary and metastatic prostate cancer as defined by cell surface CD profile. 1550 25


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