Effects of All‐<i>trans</i> Retinoic Acid on Choriocarcinoma Cells <i>in vitro</i>*

Yamada, Satoru; Okamoto, Tatsuro; Nakanishi, Tōru; Nomura, Seiji; Tsutsumi, Yutaka

doi:10.1111/j.1447-0756.1997.tb00820.x

Cited by 3 publications

(2 citation statements)

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“…[24][25][26] Expression of receptor to retinoic acid has been shown in clinical samples of CCA, and JEG-3, a human CCA cell line, also produces active retinoids. [27][28][29][30] In monolayer culture of a CCA cell line, with the use of a 3-(4.5-dimethylthiazol-2-yl)-2.5-diphenyltetrozoliumbromide-based cell proliferation assay, it was shown that ATRA could inhibit cell proliferation and enhance the effect of standard chemotherapeutic agents, such as methotrexate or actinomycin D. 27 Retinoids may thus be useful in the treatment for trophoblastic malignancy, including CCA. The mechanisms of the action of retinoic acid in CCA, however, remain unclear.…”

Section: Discussionmentioning

confidence: 99%

“…This hypothesis was supported by previous reports documenting the induction of giant-cell formation 38 and the secretion of human chorionic gonadotropin, both related to differentiation into syncytiotrophoblasts, after the addition of retinoic acid. 27 39 40 Little is known about the effect of ATRA in the invasiveness of CCA. Our results showed that ATRA can effectively inhibit JEG cell invasion in the cell invasion chamber.…”

Section: Discussionmentioning

confidence: 99%

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Effect of all-transretinoic acid on tissue dynamics of choriocarcinoma cell lines: an organotypic model

Chiu

Feng

Benbrook³

et al. 2006

J Clin Pathol

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Background: All-trans retinoic acid (ATRA) is a natural vitamin A derivative that has a profound effect on the regulation of cell growth, differentiation and death. Aim: To investigate the tissue dynamic and cellular invasion effects of ATRA in choriocarcinoma (CCA), an aggressive trophoblastic tumour, by using a three-dimensional organotypic culture model system and cell invasion assay, respectively. Methods: An organotypic culture model of two CCA cell lines, JAR and JEG, was established. The effects of 1 mM ATRA on proliferation, differentiation and apoptosis on this CCA model were assessed by morphological assessment of the mitotic and apoptotic figures as well as by Ki-67 and caspase-related M30 cytoDeath antibody immunohistochemistry and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay. The effect of ATRA on p53 and its regulated protein product, WAF1/Cip1, was also evaluated with DO7 and p21 WAF1 antibodies, respectively. Moreover, the effect of ATRA on cellular (CCA) invasion was also investigated with Cell Invasion Kit on the JEG cell line. WAF1 (p,0.0001) immunoreactivity. 1.5 mM ATRA was found to effectively inhibit JEG cell invasion in the cell invasion assay. Conclusion: ATRA treatment was found to inhibit invasion and proliferation and enhance apoptosis, probably by the activation of caspases and induction of differentiation. ATRA and synthetic retinoids may be alternative agents for the treatment of CCA.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effect of all-transretinoic acid on tissue dynamics of choriocarcinoma cell lines: an organotypic model

Chiu

Feng

Benbrook³

et al. 2006

J Clin Pathol

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Human choriocarcinoma cell line JEG-3 produces and secretes active retinoids from retinol

Blanchon

Sauvant²,

Båvik³

et al. 2002

Molecular Human Reproduction

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Vitamin A (retinol) and its active derivatives (the retinoids) are essential for growth and development of the mammalian fetus. Maternally-derived retinol has to pass through the placenta to reach the developing fetus. Despite its apparent importance, little is known about placental metabolism of retinol, and particularly placental production and/or secretion of active retinoids. It has been previously considered that retinoids are recruited from the uterine environment to influence placental development and function during gestation. We have studied retinoid metabolism in the human choriocarcinoma cell line JEG-3 and demonstrate, for the first time, that active retinoids are produced endogenously by the JEG-3 cell line from retinol. These retinoids induce gene expression from a retinoic acid-responsive enhancer element reporter plasmid and modulate placental transglutaminase activity. Furthermore, retinoids are secreted from JEG-3, as shown by the activation of retinoic acid-responsive beta lacZ reporter cells grown in conditioned media. These results suggest that there could be an active role for trophoblast-derived retinoids during human development.

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Angiogenesis in gynecological oncology-mechanism of tumor progression and therapeutic targets

Rasila¹,

Burger²,

Smith³

et al. 2005

Int J Gynecol Cancer

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The purpose of this article is to review the current literature pertaining to various angiogenic stimulators and angiogenesis inhibitors in gynecological malignancies and the relevance of these markers in the prognosis of these diseases. We also summarize the antiangiogenic drugs currently in development and in clinical use in gynecological oncology. The information was obtained from a computer search of MEDLINE for studies published in the English language regarding angiogenesis and angiogenesis inhibitors in gynecological malignancies between 1970 and December 2003; additional sources were identified through cross-referencing. In ovarian cancer, various different angiogenic activators have been found to correlate with microvessed density (MVD), stage, lymph node and peritoneal metastasis, and survival. In cervical cancer, correlation has been seen between increased angiogenic markers and stage, grade, tumor size, and survival. Studies in endometriat cancer show correlation of angiogenic markers with stage, grade, MVD, and survival. Whereas, in gestational trophoblastic neoplasm (GTD) only few markers have been studied, and some correlated with progression. Information on anti angiogenic drugs currently in ongoing and upcoming trials in gynecological malignancies is also presented. Angiogenesis factors may have a prognostic role to play in patients with gynecological cancers and should continue to be investigated as clinically useful tumor markers. Antiangiogenic-targeted therapies offer an attractive strategy for clinical investigation in gynecologic oncology.

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Effects of All‐trans Retinoic Acid on Choriocarcinoma Cells *in vitro**

Abstract: The anticancer activity presented here appears to warrant further evaluation of all-trans RA as adjuvant therapy for choriocarcinoma.

Cited by 3 publications

References 20 publications

Effect of all-transretinoic acid on tissue dynamics of choriocarcinoma cell lines: an organotypic model

Effect of all-transretinoic acid on tissue dynamics of choriocarcinoma cell lines: an organotypic model

Human choriocarcinoma cell line JEG-3 produces and secretes active retinoids from retinol

Angiogenesis in gynecological oncology-mechanism of tumor progression and therapeutic targets

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Effects of All‐trans Retinoic Acid on Choriocarcinoma Cells in vitro*

Abstract: The anticancer activity presented here appears to warrant further evaluation of all-trans RA as adjuvant therapy for choriocarcinoma.

Cited by 3 publications

References 20 publications

Effect of all-transretinoic acid on tissue dynamics of choriocarcinoma cell lines: an organotypic model

Effect of all-transretinoic acid on tissue dynamics of choriocarcinoma cell lines: an organotypic model

Human choriocarcinoma cell line JEG-3 produces and secretes active retinoids from retinol

Angiogenesis in gynecological oncology-mechanism of tumor progression and therapeutic targets

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Product

Resources

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Effects of All‐trans Retinoic Acid on Choriocarcinoma Cells *in vitro**