An experimental model of ovarian carcinoma: More than just genetics

Comment on: Induction of high grade serous carcinoma in human ovarian surface epithelial cells using combined genetic elements and peritoneal microenvironment. Zheng J, et al. Cell Cycle 2010; 9:In press.published_or_final_versio

Growth and endocrine disrupting effects of the mycotoxins zeralenone and aflatoxin B1 on breast cancer cells

Zearalenone (ZEA) and aflatoxin B1 (AFB1) are secondary metabolites produced by the fungi Fusarium and Aspergillus respectively. ZEA is proven to be an estrogenic endocrine disruptor since 1950s, while AFB1 is recently found to disrupt steroidogenesis in placenta. Both mycotoxins are constant contaminants of cereals worldwide and can both be found at significant levels in human plasma/urine of people in developing countries. Due to the co-occurrence of ZEA and AFB1 in food and human samples and the possibility of endocrine disruptors to modulate the growth of hormonal dependent breast cancer, we hypothesized that exposure to ZEA and AFB1 would affect the growth and cell cycle progression of breast cancer cells by modulating gene expressions and disrupting steroidogenesis and hormone …postprin

A novel p70 S6 kinase-microRNA biogenesis axis mediates multicellular spheroid formation in ovarian cancer progression

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Ginseng: A panacea linking East Asia and North America?

The Supplement title: The Art and Science of Traditional Medicine Part 3: The Global Impact of Traditional Medicinepostprin

The Role of Endocrine G Protein-Coupled Receptors in Ovarian Cancer Progression

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p70 S6 kinase drives ovarian cancer metastasis through multicellular spheroid-peritoneum interaction and P-cadherin/β1 integrin signaling activation

Peritoneal dissemination as a manifestation of ovarian cancer is an adverse prognostic factor associated with poor clinical outcome, and is thus a potentially promising target for improved treatment. Sphere forming cells (multicellular spheroids) present in malignant ascites of patients with ovarian cancer represent a major impediment to effective treatment. p70 S6 kinase (p70S6K), which is a downstream effector of mammalian target of rapamycin, is frequently hyperactivated in human ovarian cancer. Here, we identified p70S6K as an important regulator for the seeding and successful colonization of ovarian cancer spheroids on the peritoneum. Furthermore, we provided evidence for the existence of a novel crosstalk between P-cadherin and β1 integrin, which was crucial for the high degree of specificity in cell adhesion. In particular, we demonstrated that the upregulation of mature β1 integrin occurred as a consequence of P-cadherin expression through the induction of the Golgi glycosyltransferase, ST6Gal-I, which mediated β1 integrin hypersialylation. Loss of p70S6K or targeting the P-cadherin/β1-integrin interplay could significantly attenuate the metastatic spread onto the peritoneum in vivo. These findings establish a new role for p70S6K in tumor spheroid-mesothelium communication in ovarian cancer and provide a preclinical rationale for targeting p70S6K as a new avenue for microenvironment-based therapeutic strategy.published_or_final_versio

Proteomic analysis of a preneoplastic phenotype in ovarian surface epithelial cells derived from prophylactic oophorectomies

Objective. To study the pattern of protein expression associated with a predisposition to develop ovarian cancer. Methods. Prophylactic oophorectomy is used to prevent ovarian carcinoma in high-risk populations who have a strong family history of breast/ovarian cancer. In ovarian specimens of these women, the ovarian surface epithelium (OSE), which is tissue of origin of epithelial ovarian cancer, often shows altered morphology, growth patterns and differentiation features that are believed to be preneoplastic. This study has used a proteomic approach, based on two-dimensional gel electrophoresis and mass spectrometry, to compare the protein profiles of OSE from women with a history of familial ovarian cancer (FH-OSE), i.e., at least two first-degree relatives with such cancer and/or testing positive for BRCA1 mutations, to those without such history (NFH-OSE). Results. Of >1500 protein spots, there were 8 proteins whose levels were significantly altered in FH-OSE. Three were known ovarian tumor associated proteins, others were novel changes. A number of the alterations seen were accompanied with protein modifications and have not been previously reported. There was a predominance of sequences related to the stress response pathway. Differential expression of selected genes was confirmed by Western blotting and real-time reverse transcription polymerase chain reaction. Conclusions. Our findings define the OSE phenotype of women at a high risk of developing ovarian cancer. Protein alterations seen in these tissues may represent an early, irreversible, non-mutational step in ovarian epithelial neoplastic progression and may be potential early and sensitive markers for the evaluation of cancer risk. © 2005 Elsevier Inc. All rights reserved.postprin

Nanomechanical measurement of adhesion and migration of leukemia cells with phorbol 12-myristate 13-acetate treatment

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ERK1/2, PI3K and p70S6K are important mediators for HGF-induced migration and invasion in human ovarian cancer cells

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Mechanical oscillations enhance gene delivery into suspended cells

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