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Ovarian Serous Carcinoma (ovarian + serous_carcinoma)

Distribution by Scientific Domains

Medical Sciences	80%

Selected Abstracts

Structure of the human Nac1 POZ domain

ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 5 2009
Mark A. Stead
Nac1 is a POZ-domain transcription factor that is involved in the self-renewal of embryonic stem cells. It is overexpressed in ovarian serous carcinoma and targeting the interactions of its POZ domain is a potential therapeutic strategy. Nac1 lacks a zinc-finger DNA-binding domain and thereby differs from most other POZ-domain transcription factors. Here, the crystal structure of the Nac1 POZ domain at 2.1,Å resolution is reported. The Nac1 POZ domain crystallized as a dimer in which the interaction interfaces between subunits resemble those found in the POZ-zinc finger transcription factors. The organization of the Nac1 POZ-domain core resembles reported POZ-domain structures, whereas the C-terminus differs markedly. The C-terminal ,-helix of the Nac1 POZ domain is shorter than that observed in most other POZ-domain transcription factors; variation in the organization of this region may be a general feature of POZ-domain structures. [source]

Expression of c-ABL, c-KIT, and platelet-derived growth factor receptor-, in ovarian serous carcinoma and normal ovarian surface epithelium

CANCER, Issue 4 2003
Rosemarie E. Schmandt Ph.D.
Abstract BACKGROUND Tyrosine kinases, such as c-KIT, c-ABL, and platelet-derived growth factor-beta (PDGFR-,), are important regulators of cell growth. Highly potent and selective inhibitors of tyrosine kinases are being investigated as alternatives to standard chemotherapy. One such inhibitor, imatinib mesylate, is being used to treat gastrointestinal stromal tumors and chronic myelogenous leukemia. Ovarian carcinomas frequently develop resistance to conventional chemotherapeutic agents. Immunohistochemical expression of c-ABL, PDGFR-,, and c-KIT was evaluated in ovarian carcinomas to determine whether treatment with imatinib mesylate might be feasible. METHODS The expression of c-ABL, c-KIT, and PDGFR-, in tumors was evaluated by immunohistochemical analysis of 52 ovarian serous carcinomas, including 21 low-grade (well differentiated) and 31 high-grade (poorly differentiated) tumors. Fourteen normal ovaries were also evaluated. RESULTS In normal ovarian surface epithelium, c-ABL was expressed universally. PDGFR-, was expressed in the majority (93%) of samples of normal ovarian epithelium, whereas the c-KIT protein was undetectable in normal ovarian surface epithelium. Overall, c-ABL was expressed in 71% of serous carcinomas. c-ABL was expressed more frequently in the low-grade serous carcinomas (81%) compared with the high-grade serous carcinomas (65%). PDGFR-, expression was observed in 81% of serous carcinomas overall and was observed more frequently in higher-grade tumors. c-KIT immunohistochemical staining was absent in low-grade tumors but was present in 26% of high-grade serous carcinomas. CONCLUSIONS The majority of ovarian serous carcinomas express one or more of the kinases targeted by the tyrosine kinase inhibitor, imatinib mesylate, suggesting the potential usefulness of this drug in the treatment of ovarian carcinoma. Cancer 2003;98:758,64. © 2003 American Cancer Society. DOI 10.1002/cncr.11561 [source]

Prognostic significance of Notch 3 gene expression in ovarian serous carcinoma

CANCER SCIENCE, Issue 9 2010
Sang G. Jung
The Notch signaling pathway is an important cell signaling system, which regulates cell differentiation, proliferation, and apoptosis, and is aberrantly activated in a wide range of cancer, including ovarian cancers. However, it remains unclear as to whether Notch signaling plays a role in the progression and prognosis of ovarian cancer. We examined the mRNA and protein expression of Notch 3, Jagged 1, and Jagged 2 in 98 ovarian epithelial tumors via real-time PCR and in 175 tumors with immunohistochemical analysis, and then correlated their expression levels with clinicopathological parameters and patient survival. In this study, we detected high levels of Notch3 mRNA and protein expression especially in serous ovarian carcinomas compared to their benign counterparts, accompanied by a positive correlation with the expressions of Jagged 1 and Jagged 2. High levels of Notch 3 mRNA expression (>2-fold than that of benign tumor) were noted in 63% of the serous carcinomas (mean level: 17-fold, P = 0.032). Additionally, Notch 3 protein overexpression was significantly associated with advanced stage (P = 0.0008), lymph node (P = 0.001), and distant metastasis (P = 0.003). Notably, high Notch 3 mRNA and protein expressions were correlated with chemoresistance (P = 0.033) and poor overall survival (P = 0.027, P = 0.042) in these patients. Our results indicate that the Notch 3 signaling pathway is involved in the tumor progression of ovarian serous carcinoma, and higher Notch 3 expression may be an independent poor prognostic factor in this subset of tumors. (Cancer Sci 2010) [source]