Effect of methotrexate on the growth and human chorionic gonadotropin secretion of human choriocarcinoma cell lines in vitro

Sekiya, Souei; Kaiho, T; Shirotake, S; Iwasawa, H.; Takeda, Bin; Takamizawa, H

doi:10.1016/0002-9378(83)90927-4

Cited by 23 publications

(6 citation statements)

References 7 publications

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“…The biphasic pattern of f-hCG levels observed in our series is similar to that described in other clinical studies of MTX-treated EPs [10] as well as in in vitro tissue cultures [23][24][25]27] and in animal models [28]. A transient rise in 1-hCG titers has also been noted in patients receiving MTX for gestational trophoblastic disease [29].…”

Section: Discussionsupporting

confidence: 87%

“…The average number of determinations for MTX-treated patients was 4.5 (range 2-11). The average ,3-hCG titer obtained within 24 hours of the first MTX injection was 3,140 mIU/mL (range 201-9,696 mIU/mL) and the average maximum P-hCG titer in failed MTXtreated EPs was 5,243 mIU/mL (range 24-13,940 mIU/mL). Within 24 hours of surgery the average P-hCG titer was 3,276 mIU/mL for 11 of the MTXtreated patients; one patient did not have a recorded ,B-hCG titer within 72 hours of the definitive surgical procedure.…”

Section: Resultsmentioning

confidence: 93%

“…In the current series, the presence of trophoblastic atypia did not correlate with the presence or degree of villous necrosis in either the MTX-exposed or control EPs. In vitro tissue cultures of normal trophoblasts and choriocarcinoma cell lines incubated with MTX show linear inhibition of growth with increasing MTX concentration as well as several morphologic changes, including the appearance of vacuoles and granules in the cytoplasm, and enlargement of the nuclei [23][24][25]. Cytologic atypia of trophoblasts (including nuclear enlargement, irregular nuclear outlines, and hyperchromasia) constitutes one of the diagnostic features of molar gestations [26].…”

Section: Discussionmentioning

confidence: 99%

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Failed Methotrexate-Treated Ectopic Pregnancies: Clinicopathologic Correlations

Doss¹,

Ramirez²,

Lawrence

1997

Int J Surg Pathol

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Methotrexate (MTX) administration as an alternative to surgical therapy for unruptured ectopic pregnancies (EPs) has a 5-11% failure rate. The histologic findings in surgical specimens from patients for whom MTX therapy failed have not been extensively described. Review of pathology records from January 1991 through June 1996 revealed 12 MTX-treated tubal EPs that subsequently required surgical intervention. Clinical data and histologic findings were compared with those from tubal EPs from maternal-age-and gestational-age-matched controls. Semiquantitative observations of chorionic villous morphology were assessed by a senior pathologist unaware of the treatment regimens. The average maternal age was 27 years and the mean gestational age was 9 weeks. Patients received one to two intramuscular injections of MTX (50 mg/M2) and were followed up with serial serum beta-human chorionic gonadotropin (f-hCG) determinations. P-hCG levels fell from presentation to surgical intervention in 36.4% of MTX-treated patients, increased in 9.1 %, and rose then fell in 54.5%. Peak r-hCG titers were significantly higher in MTX-exposed patients as compared with controls. There was no correlation between ,3-hCG profile and villous morphology. Sixty-seven percent of MTX-treated EPs showed significant trophoblastic atypia as compared with 25% of control cases. Atypical villous trophoblasts had enlarged nuclei with irregular contours, smudged chromatin, and prominent nucleoli. There were no significant differences between failed MTX-exposed EPs and controls in terms of the presence or degree of villous necrosis, trophoblastic vacuolization, or embryonic development. Chorionic villous morphology in failed MTX-treated EPs showed no significant differences from that of nontreated EPs except for a trend toward increased trophoblastic atypia, features that may be confused with early gestational trophoblastic disease. Failed MTX-treated EPs may represent a subset of gestations that are resistant to MTX. As the uses of MTX are expanded to encompass the termination of early intrauterine pregnancies, the recognition of possible treatment-related alterations in the histologic appearance of chorionic villi, trophoblasts, and implantation sites will be pertinent to avoid misdiagnosis. Int J Surg Pathol 5(3/4): [83][84][85][86][87][88][89][90][91][92][93][94] 1997

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Section: Discussionsupporting

confidence: 87%

Section: Resultsmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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Failed Methotrexate-Treated Ectopic Pregnancies: Clinicopathologic Correlations

Doss¹,

Ramirez²,

Lawrence

1997

Int J Surg Pathol

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“…In this regard, increased production of human chorionic gonadotropin (hCG) has been widely used as a marker of differentiated trophoblast f~n c t i o n .~ Often cell growth and differentiation are a mutually exclusive rela-tion~hip.~ Accordingly, in trophoblast-derived choriocarcinoma cells, inhibitors of cell proliferation induced expression of many differentiation characteristics. [6][7][8][9][10] Previously, ethanol treatment has been shown to stimulate hCG production in cultured term human placental trophoblasts." In addition, ethanol treatment has been shown to alter production of steroid hormones in JEG-3 choriocarcinoma cells.12 Because hormone production is a marker of differentiation, ethanol may induce alterations in cellular growth and/or differentiation.…”

mentioning

confidence: 99%

Ethanol and Mitotic Inhibitors Promote Differentiation of Trophoblastic Cells

Karl

Harvey

Fisher

1996

Alcoholism Clin & Exp Res

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Chronic ethanol abuse during pregnancy can cause fetal injury. A contributing factor in this fetal injury may be the effect of ethanol on the placenta. Ethanol treatment increases human chorionic gonadotropin (hCG) production by cultured human placental trophoblasts. In this study, we show that ethanol treatment reduces total DNA and total protein while stimulating hCG production in term trophoblasts. Ethanol treatment inhibits growth in rapidly proliferating trophoblastic cells from a first trimester placenta and JEG-3 choriocarcinoma cells. In both cell types, the normal increases in total DNA were inhibited in an ethanol dose-dependent manner. Normal increases in total protein were inhibited as well. In contrast, hCG production, an indicator of differentiation, was stimulated by ethanol treatment. Treatment of JEG-3 cells with antimitogenic agents, methotrexate (MTX) or cytosine arabinoside (Ara-C), inhibited cell growth as indicated by decreased total DNA and total protein accumulation. Similar to that with ethanol treatment, inhibition of cell proliferation was accompanied by increases in hCG production. Taken together, these data suggest that one mechanism by which ethanol increases hCG production in human placental trophoblasts may involve alterations in cellular growth and/or differentiation; such alterations may also occur in other proliferating cells in the growing fetus.

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“…MTX has recently shown its effectiveness in inhibiting normal trophoblastic cell growth in vitro and has for a long period been the elected agent for the treatment of gestational trophoblastic disease [8][9][10]. MTX may be effective in inducing tubal abortion or resorption of ectopic trophoblastic tissue, and in combination with citrovarum rescue, represents an exciting alternative for the treatment of ectopic pregnancy in selected cases.…”

Section: Discussionmentioning

confidence: 99%

Effects of Methotrexate on Rabbit Oviducts and on Cell Cultures of Bovine Oviduct Epithelium

Tepper

Nahum²,

Rahamim³

et al. 1992

Gynecol Obstet Invest

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The influence of a local injection of 0.05 ml/kg weight of 8 mg/ml methotrexate (MTX) was evaluated in 6 rabbit oviducts and compared with saline injections to the contralateral oviducts. Cell cultures of bovine oviducts were incubated in vitro for 7 days and then incubated for 24 h with 100-nmol MTX. Forty-eight and 72 h following the exposure to MTX, the treated and control cultures were harvested. Specimens and cultures were examined by light and scanning electron microscopy. In the in vivo cohort, no differences were observed between MTX and control groups. However, in MTX-treated cell culture, ciliated cells demonstrated partially adherent cilia in about 30% of the cells. The effect of MTX observed only in vitro treated cells may be due to the rapid proliferation of epithelial cells in culture which does not represent the physiological role of the oviduct in vivo.

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Effect of methotrexate on the growth and human chorionic gonadotropin secretion of human choriocarcinoma cell lines in vitro

Cited by 23 publications

References 7 publications

Failed Methotrexate-Treated Ectopic Pregnancies: Clinicopathologic Correlations

Failed Methotrexate-Treated Ectopic Pregnancies: Clinicopathologic Correlations

Ethanol and Mitotic Inhibitors Promote Differentiation of Trophoblastic Cells

Effects of Methotrexate on Rabbit Oviducts and on Cell Cultures of Bovine Oviduct Epithelium

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