Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lymphangioma (LA) and congenital pulmonary lymphangiectasis (CPL) are part of a spectrum of lymphatic disorders less well characterized than other vascular tumors and malformations. Recent studies showed proliferative and involutional growth phases for hemangiomas that distinguish them from malformations. We investigated immunohistochemical reactivity and proliferative activity to determine whether a similar diagnostically/prognostically useful pattern exists for LA, comparing LA with CPL as a malformative lesion. Immunohistochemical tests for vimentin, Factor VIII-related protein, CD31, CD34, CD45RO, smooth muscle actin, Type IV collagen, MIB-1, bcl-2, and topoisomerase IIalpha were performed on 20 LAs and 10 cases of CPL. Giemsa staining was also performed to quantitate mast cells. Clinicopathologic correlation was performed by medical record review. LA and CPL shared a similar immunohistochemical profile for vimentin, Factor VIII-related protein, CD31, CD34, smooth muscle actin, CD34, and, to a lesser extent, CD45RO. CD31 and CD34 displayed the most uniform pattern of endothelial reactivity, although CD34 had high background staining. bcl-2 was negative. Four LAs exhibited focal low reactivity for MIB-1 and topoisomerase IIalpha; recent infection and thrombosis were associated conditions. LAs displayed seven-fold more mast cells and more reactive T lymphocytes than did cases of CPL. LA and CPL had similar immunohistochemical profiles; LA resembled vascular malformations more than hemangiomas. CD31 and CD34 were useful for detection of small lymphatics at resection margins of LA, a feature associated with recurrence. MIB-1 and topoisomerase IIalpha expression were associated with inflammatory, thrombotic, or reactive processes and were not diagnostically useful. Abundant mast cells, which also were noted in other soft tissue neoplasms, prompt speculation concerning their role in the growth of LAs.
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PMID:Lymphangioma and congenital pulmonary lymphangiectasis: a histologic, immunohistochemical, and clinicopathologic comparison. 1039 31

To confirm whether human cancer-induced stromal cells are derived from bone marrow, bone marrow (BM) cells obtained from beta-galactosidase transgenic and recombination activating gene 1 (RAG-1) deficient double-mutant mice (H-2b) were transplanted into sublethally irradiated severe combined immunodeficient (SCID) mice (H-2d). The human pancreatic cancer cell line Capan-1 was subcutaneously xenotransplanted into SCID recipients and stromal formation was analyzed on day 14 and on day 28. Immunohistochemical and immunofluorescence studies revealed that BM-derived endothelial cells (X-gal/CD31 or H-2b/CD31 double-positive cells) and myofibroblasts (X-gal/alpha-smooth muscle actin or H-2b/alpha-smooth muscle actin double-positive cells) were present within and around the cancer nests. On day 14, the frequencies of BM-derived endothelial cells and BM-derived myofibroblasts were 25.3+/-4.4% and 12.7+/-9.6%, respectively. On day 28, the frequency of BM-derived endothelial cells was 26.7+/-9.7%, which was similar to the value on day 14. However, the frequency of BM-derived myofibroblasts was significantly higher (39.8+/-17.1%) on day 28 than on day 14 (P<0.05). The topoisomerase IIalpha-positive ratio was 2.2+/-1.2% for the H-2b-positive myofibroblasts, as opposed to only 0.3+/-0.4% for the H-2b-negative myofibroblasts, significant proliferative activity was observed in the BM-derived myofibroblasts (P<0.05). Our results indicate that BM-derived myofibroblasts become a major component of cancer-induced stromal cells in the later stage of tumor development.
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PMID:Bone-marrow-derived myofibroblasts contribute to the cancer-induced stromal reaction. 1294 87

Engulfment of apoptotic cells is regulated by 'eat me' and 'don't eat me' signals on the cell surface. Alterations to the 'eat me' signals have been well described; however, very little is known about the 'don't eat me' signals on the cell surface during apoptosis. In the present study, apoptosis of Jurkat cells was induced by treatment with topoisomerase II inhibitor etoposide, and then the CD31 and CD47 levels on the apoptotic cell surface and in microparticles were estimated by flow cytometry and immunoblotting methods in the presence of caspase, metalloproteinase, and Rho-associated coiled-coil containing protein kinase 1 (ROCK1) inhibitors. The CD31 and CD47 levels on the cell surface of apoptotic Jurkat cells had decreased after treatment with etoposide. These decreases in CD31 and CD47 levels on the apoptotic cell surface were almost completely suppressed by the caspase 3 inhibitor, Ac-DEVD-CHO, and partially suppressed by caspase 8 (Ac-IETD-CHO) and caspase 9 (Ac-LEHE-CHO) inhibitors but not by the metalloproteinase inhibitors GM6001 and TAPI-0. Microparticle counts in culture supernatants were higher during etoposide-induced apoptosis. The ROCK1 inhibitor, Y27632, suppressed blebbing formation and microparticle release. Moreover, flow cytometry and immunoblotting revealed CD31 and CD47 in the microparticles. These results indicate that CD31 and CD47 were released by the apoptotic Jurkat cells into the culture supernatant in microparticles, but not in soluble forms, resulting in decreased levels on the apoptotic cell surface.
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PMID:Decreases in CD31 and CD47 levels on the cell surface during etoposide-induced Jurkat cell apoptosis. 2213 Feb 38