Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:5.99.1.3 (topoisomerase)
 9,911 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brain tumors account for approximately 20% of all childhood cancers, and are the leading cause of cancer morbidity and mortality among children. Although numerous demographic, clinical and therapeutic parameters have been identified over the past few years that have significant prognostic bearing for some pediatric brain tumors, predicting the clinical course and outcome among children with central nervous system tumors is still difficult. A survey of publications on prognosis-related histopathological and immunohistochemical features among pediatric brain tumors revealed 172 series, of which 91 presented statistically significant outcome-associated parameters as defined by a P value of less than 0.05. Most investigations revealing significant prognosis-related markers were performed on medulloblastomas (30 publications), ependymomas (25) and astrocytic tumors (18). In total, 16 cohorts consisted of more than 100 cases (5 on ependymomas, 3 each on medulloblastomas and astrocytic tumors). On the other hand, there were also 13 series with fewer than 20 cases (5 on medulloblastomas). Potentially prognostic histopathological markers vary among different entities and consist of assessment of necroses, mitoses, differentiation, vascular proliferation, and growth pattern, whereas immunohistochemical features include proliferation markers (Ki-67, MIB-1), expression of oncogenes/tumor suppressor genes and their proteins (TP53, c-erbB2), growth factor and hormonal receptors (VEGF, EGFR, HER2, HER4, ErbB-2), cell cycle genes (p27, p14ARF) and cell adhesion molecules, as well as factors potentially related to therapeutic resistance (DNA topoisomerase IIalpha, metallothionein, P-glycoprotein, tenascin). This review discusses the prognostic potential of histopathological and immunohistochemical markers that can be investigated by the practicing neuropathologist as part of the routine diagnostic workload, and scrutinizes their benefit for predicting therapy response and patient outcome among children with brain tumors.
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PMID:Prognosis-related histomorphological and immunohistochemical markers in central nervous system tumors of childhood and adolescence. 1564 46

The aim of this study was to evaluate the role of several biological and histological markers (topoisomerase IIalpha, MIB-1, E2F, apoptotic index, APE/ref-1, p53, Her-2/neu, estrogen and porgesterone receptors, and histological grading) as predictors of pathologic response after anthracycline-based chemotherapy for breast cancer. A series of 50 consecutive breast cancer patients receiving anthracycline-based primary chemotherapy were retrospectively studied. Biological markers were assessed by immunohistochemistry (and by TUNEL assay for apoptotic index) in pre-treatment core biopsies and post-treatment surgical samples. The expression of topoisomerase IIalpha, E2F, MIB-1, estrogen and progesterone receptors decreased, while APE/ref-1 staining increased after treatment. Higher topoisomerase IIalpha (P=0.007) and lower APE/ref-1 (P=0.04) expression were associated with better pathologic response.
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PMID:Topoisomerase IIalpha and APE/ref-1 are associated with pathologic response to primary anthracycline-based chemotherapy for breast cancer. 1591 Nov 9

Medulloblastoma (MB) is the most common malignant neuroepithelial tumor of childhood. The DNA topoisomerase II (Topo II) inhibitor etoposide has been widely used for the treatment of MBs; however, it remains unknown whether MB cells are more sensitive to etoposide than other malignant neuroepithelial tumor cells. In this study, we tested the chemosensitivities of malignant neuroepithelial tumors (26 glioblastomas, 9 anaplastic astrocytomas, and 5 MBs) to etoposide and vincristine using the succinate dehydrogenase inhibition test and found that MB cells are more sensitive to etoposide and more resistant to vincristine than other tumor cells. We performed quantitative reverse-transcription polymerase chain reaction to evaluate the expression of genes related to etoposide sensitivity, and found co-overexpression of DNA topoisomerase II (Topo II) alpha and beta mRNA in MBs. In addition, the levels of Topo IIalpha and beta mRNA in these tumors correlated with etoposide sensitivity. Immunohistochemical studies using surgical samples of these tumors demonstrated that the percentages of Topo IIalpha immunopositive cells (Topo IIalpha labeling index) correlated with those of Ki-67 immunopositive cells (MIB-1 labeling index); however, neither the Topo IIalpha nor the MIB-1 labeling index correlated with the levels of Topo IIalpha mRNA or etoposide sensitivity. Based on these observations, Topo IIalpha and beta mRNA expression, but not the Topo IIalpha labeling index, might be a useful marker for sensitivity to etoposide in human malignant neuroepithelial tumors.
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PMID:Enhanced expression of DNA topoisomerase II genes in human medulloblastoma and its possible association with etoposide sensitivity. 1736 31

Vascular endothelial growth factor (VEGF) is considered to be a major regulator of angiogenesis in various brain tumors. In this study, we determined the expression levels of VEGF, and vascular endothelial growth factor receptor (VEGFR)-1 and -2 mRNA in 46 intracranial schwannomas by quantitative real-time PCR, and correlated these with various clinical factors or other molecular markers. We found that these tumors expressed significant amounts of VEGF mRNA in comparison with other brain tumors, including malignant gliomas and meningiomas. In addition, we performed immunohistochemical studies for VEGF and VEGFR-1, and confirmed that these tumors prominently express these proteins. The expression levels of VEGF and VEGFR-1 mRNA in recurrent tumors were higher than those in primary tumors. When we divided patients into two groups according to VEGF mRNA expression in the tumor, there was no significant difference in patient age, gender, or cranial nerves of origin between groups; however, the tumor volume tended to be larger in the high VEGF group than in the low VEGF group. The levels of VEGFR-1 mRNA and neurofibromatosis-2 mRNA in the high VEGF group were significantly greater than those in the low VEGF group. Levels of VEGFR-2 mRNA and DNA topoisomerase IIalpha mRNA, and the MIB-1 labeling index in the high VEGF group were slightly higher than those in the low VEGF group; however, the difference was not statistically significant. Based on these observations, the significance of VEGF and its receptor genes in intracranial schwannomas is discussed.
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PMID:Expression of VEGF and its receptor genes in intracranial schwannomas. 1757 36

Giant adenomas comprise a clinical/therapeutic subset of pituitary adenomas that pose a surgical challenge. The study population consisted of 28 patients who had giant pituitary adenomas, which are defined as tumors with a diameter greater than 5cm. Clinically, five tumors (18%) were endocrinologically functional and 23 (82%) were not. During surgery, one tumor was radically excised, four were subtotally excised, 12 were partially excised, and 11 were biopsied. All of the tumors showed typical histological features of pituitary adenoma. Of the 23 clinically non-functional adenomas, 18 were gonadotrophic tumors, four were null cell adenomas and one was a silent corticotroph adenoma. The MIB-1 labeling indices ranged from 0.1% to 2.0%. The mean topoisomerase labeling index was 0.75%. Microvessel density ranged from 0.42% to 5.55%, and there was moderately intense immunostaining for vascular endothelial growth factor. The present study found giant adenomas to be invasive but slow growing, histologically benign and often gonadotrophic in subtype.
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PMID:Clinicopathologic correlates of giant pituitary adenomas. 1928 7

Breast cancer is not a single entity. This study therefore aimed to identify differences in the impacts of anticancer agents and predictive factors between different breast cancer subtypes. A total of 234 patients with luminal (n = 109), luminal-HER2 (L-H, n = 29), HER-2 (n = 35), or triple negative (TN, n = 61) breast cancer subtypes were treated with standard neoadjuvant chemotherapy consisting of an anthracycline and/or taxane. Pathological response and prognosis were examined in each subtype. Expression levels of estrogen and progesterone receptors, HER-2, nuclear grade, MIB-1, p53, topoisomerase IIalpha (topoIIalpha), cytokeratin (CK) 5/6, and epidermal growth factor receptor (EGFR) were examined in association with quasipathological complete response (QpCR). QpCR rates were 9.1% (10/109) in luminal, 45% (13/29) in L-H, 37% (13/35) in HER2, and 54.1% (33/61) in TN. Non-QpCR patients showed significantly poorer 3-year disease-free survival than QpCR patients in TN, but not in patients with other subtypes. No factors were associated with QpCR in luminal patients. Patients with higher nuclear grade were more likely to achieve QpCR in L-H. The proliferative markers MIB-1 and topoIlalpha had opposite impacts on pathological response in HER-2 and TN. The QpCR rate was significantly higher in TN lacking CK5/6 and/or EGFR expression, defined as nonbasal subtype, compared with basal subtype (p = 0.049). Cytotoxic anticancer agents were associated with different responses in different breast cancer subtypes. Identifying basal-type cancer and further subdivision of nonbasal types is important for treating TN patients.
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PMID:Impacts and predictors of cytotoxic anticancer agents in different breast cancer subtypes. 2319 13


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