Open AccessJournal Article
Loss of cellular retinol-binding protein 1 gene expression in microdissected human ovarian cancer.
TL;DR: The loss of CRBP1 expression in clinical ovarian tumor specimens is consistent with previous findings in the rat model and human ovarian cancer cell lines, and it appears to be an early event in ovarian carcinogenesis because there was no statistically significant difference in its frequency between tumor stages and grades.
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Abstract: Purpose: We have previously found that cellular retinol-binding protein 1 (CRBP1),involved in retinol transport and metabolism, is down-regulated in an in vitro rat model of ovarian cancer and in several human ovarian cancer cell lines. The aim of this study was to determine the clinical relevance of this change to human ovarian cancer. Experimental Design: A cohort of 48 frozen human serous ovarian carcinomas was evaluated for CRBP1 gene expression. Malignant ovarian epithelial cells were selectively procured by laser capture microdissection, and their CRBP1 expression was determined by real-time PCR. Immunohistochemistry for CRBP1 was performed on paraffin sections of ovarian tumors using polyclonal affinity-purified rabbit anti-CRBP1 antibody. Results: In 35% of ovarian cancer patient samples, there was no detectable CRBP1 expression by real-time PCR. The expression of CRBP1 in microdissected serous ovarian carcinomas was not related to either tumor stage ( P = 0.6839) or grade ( P = 0.9599). Quantitative PCR results were confirmed by immunohistochemistry using an antibody against CRBP1. Conclusions: The loss of CRBP1 expression in clinical ovarian tumor specimens is consistent with our previous findings in the rat model and human ovarian cancer cell lines. It appears to be an early event in ovarian carcinogenesis because there was no statistically significant difference in its frequency between tumor stages and grades. Our findings suggest that the loss of CRBP1 expression contributes to the ovarian cancer oncogenesis via altered vitamin A metabolism.
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Citations
Three biomarkers identified from serum proteomic analysis for the detection of early stage ovarian cancer
Zhen Zhang,Robert C. Bast,Yinhua Yu,Jinong Li,Lori J. Sokoll,Alex J. Rai,Jason M. Rosenzweig,Bonnie Cameron,Young Y. Wang,Xiao Ying Meng,Andrew Berchuck,Carolien van Haaften-Day,Neville F. Hacker,Henk W.A. de Bruijn,Ate G.J. van der Zee,Ian Jacobs,Eric T. Fung,Daniel W. Chan +17 more
TL;DR: These biomarkers demonstrated the potential to improve the detection of early stage ovarian cancer by demonstrating the sensitivity and specificity of a multivariate model combining the three biomarkers.
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Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair.
Yuanshu Dong,Mohamed-Ali Hakimi,Xiaowei Chen,Easwari Kumaraswamy,Neil Cooch,Andrew K. Godwin,Ramin Shiekhattar +6 more
TL;DR: In vivo, depletion of BRCC36 and BRCC45 by the small interfering RNAs resulted in increased sensitivity to ionizing radiation and defects in G2/M checkpoint, identifying BRCC as a ubiquitin E3 ligase complex that enhances cellular survival following DNA damage.
311
Gene Expression Profiles in Pancreatic Intraepithelial Neoplasia Reflect the Effects of Hedgehog Signaling on Pancreatic Ductal Epithelial Cells
Nijaguna B. Prasad,Andrew V. Biankin,Noriyoshi Fukushima,Anirban Maitra,Surajit Dhara,Abdel G. Elkahloun,Ralph H. Hruban,Michael Goggins,Steven D. Leach +8 more
TL;DR: Hedgehog pathway activation induced by transfection of immortalized human pancreatic ductal epithelial cells with Gli1 resulted in up-regulation of the majority of foregut markers seen in early PanIN lesions, suggesting that PanIN development may involve Hedgehog-mediated conversion to a gastric epithelial differentiation program.
268
Vitamin A, Cancer Treatment and Prevention: The New Role of Cellular Retinol Binding Proteins
Elena Doldo,Gaetana Costanza,Sara Agostinelli,Chiara Tarquini,Amedeo Ferlosio,Gaetano Arcuri,Daniela Passeri,Maria Giovanna Scioli,Augusto Orlandi +8 more
TL;DR: Reexpression of CRBP-1 increased retinol sensitivity and reduced viability of ovarian cancer cells in vitro, and further studies are needed to explore new therapeutic strategies aimed at restoring CR BP-1-mediated intracellularRetinol trafficking and the meaning of CRbp-1 expression in cancer patients' screening for a more personalized and efficacy retinoid therapy.
Cellular Retinol-Binding Protein I, a Regulator of Breast Epithelial Retinoic Acid Receptor Activity, Cell Differentiation, and Tumorigenicity
Eduardo F. Farias,David E. Ong,Norbert B. Ghyselinck,Shigeo Nakajo,Yuvarani S. Kuppumbatti,Rafael Mira y Lopez +5 more
TL;DR: Physiologic RAR activation is dependent on CRBP-I-mediated retinol storage, and CR BP-I downregulation chronically compromises RAR activity, leading to loss of cell differentiation and tumor progression.
85
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TL;DR: Part I: Molecular Biology of Cancer Molecular Methods in Oncology Section 1. Amplification Techniques Section 2. RNA Interference Section 3. cDNA arrays Section 4. Tissue arrays Section 5. Cytogenetics Section 6. Bioinformatics Genomics and Proteomics Molecular Targets in oncology.
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Randomized Trial of Fenretinide to Prevent Second Breast Malignancy in Women With Early Breast Cancer
Sylvie Menard,Tiziana Camerini,Luigi Mariani,Gorana Tomasic,Silvana Pilotti,Alberto Costa,Giuseppe De Palo,Umberto Veronesi +7 more
TL;DR: Fenretinide treatment of women with breast cancer for 5 years appears to have no statistically significant effect on the incidence of second breast malignancies overall, although a possible benefit was detected in premenopausal women.
Cellular retinol-binding protein I is essential for vitamin A homeostasis.
Norbert B. Ghyselinck,Claes Bavik,Vincent Sapin,Manuel Mark,Dominique Bonnier,Colette Hindelang,Andrée Dierich,Charlotte B. Nilsson,Helen Håkansson,Patrick Sauvant,Véronique Azaïs-Braesco,Maria Frasson,Serge Picaud,Pierre Chambon +13 more
TL;DR: CRBPI is indispensable for efficient RE synthesis and storage, and its absence results in a waste of ROL that is asymptomatic in vitA‐sufficient animals, but leads to a severe syndrome of vitA deficiency in animals fed a vitA-deficient diet.
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•Journal Article
A simplified method to culture human ovarian surface epithelium.
TL;DR: Improved explanation method was developed which takes advantage of the tenuous attachment of OSE to underlying tissues: the surface epithelium was scraped off the ovarian surface with a rubber scraper, generating epithelial fragments which produced monolayers in culture, with little contamination by other cell types.
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