Setsuko Goto

Intracranial metastasis of choriocarcinoma. A clinicopathologic study

In an attempt to improve the diagnosis and treatment of intracranial metastases of choriocarcinoma, the authors carried out a clinicopathologic investigation of 36 patients with choriocarcinoma metastasized in the brain. Analysis on the autopsy findings of 30 cases with documented intracranial metastases of choriocarcinoma proved neurosurgical resectability in most cases. After initiation of the clinical use of dactinomycin in 1965, 5 of 10 patients in the surgically treated group, and 1 of 17 in the group without surgery, survived for more than 6 months after development of neurologic symptoms. Intracranial metastases of choriocarcinoma should be treated as follows: (1) if symptoms of increased intracranial pressure progress to a life‐threatening situation, removal of tumor or, at least, decompression should be immediately performed; (2) multidrug chemotherapy supplemented by whole‐brain irradiation should be started within several days after surgery; and (3) if symptoms are not present, chemotherapy combined with irradiation is the first treatment of choice.

Expression of Aminopeptidase N on Human Choriocarcinoma Cells and Cell Growth Suppression by the Inhibition of Aminopeptidase N Activity

We previously found that an aminopeptidase inhibitor, ubenimex (bestatin), had a growth‐suppressive effect on Choriocarcinoma cell lines in vitro. To clarify the mechanism of this action, we investigated the expression of aminopeptidase N (AP‐N/CD13) on Choriocarcinoma cells and other human tumor cells. Two Choriocarcinoma cell lines, NaUCC‐4 and Be Wo, had higher AP‐N activity than other cell lines (358.8 and 340.2 nmol/h/106 cells, respectively), as did the human myeloid leukemia cell line, HL‐60 (373.8 nmol/h/106 cells). These Choriocarcinoma and leukemia cell lines with abundant AP‐N activity showed much higher sensitivity to bestatin (IC50 = 0.5, 2.1 and l.0μg/ml, respectively) than the other cell lines. By imniuiioblotting and immunocytochemical staining, AP‐N was detected as an approximately 165‐kDa protein and localized on the cell membrane in Choriocarcinoma cells. We also examined the effects of two other aminopeptidase inhibitors and three anti‐CD13 monoclonal antibodies (MAbs) (WM15, MCS2 and MY7) on the growth of NaUCC‐4 cells. Cell growth was markedly suppressed by the AP‐N inhibitor actinonin as well as bestatin, but not by the AP‐B inhibitor arphamenine. Of the three MAbs, only WM15, which is able to inhibit AP‐N activity, suppressed cell growth in a dose‐dependent manner. These results indicate that AP‐N inhibitors show a growth‐suppressive effect, presumably through inhibition of the enzymatic activity of AP‐N on tumor cells, and suggest that AP‐N may play important roles in the growth of certain tumors, such as Choriocarcinoma and leukemia.

Polyembryoma of ovary producing alpha-fetoprotein and HCG: Immunoperoxidase and electron microscopic study

Polyembryoma of ovary producing alpha‐fetoprotein (AFP) and human chorionic gonadotropin (HCG) was studied by indirect immunoperoxidase method for AFP and HCG, and electron microscopy. Clinically, this patient showed pseudoprecocious puberty caused by elevated HCG which is synthesized by trophoblastic cells in polyembryoma. She is put under VAC (vincristine, actinomycin‐D, cyclophosphamide) chemotherapy after operation and shows no signs of recurrence including reelevation of serum AFP at five months after operation. Embryoid bodies which we studied correspond to normal embryo at 15‐ or 16‐day stage. Immunoperoxidase study showed that AFP is synthesized by yolk sac cells of the embryoid bodies and HCG is synthesized by syncytiotrophoblastic cells. The finding about AFP synthesis suggests that normal embryo at 15‐ or 16‐day stage may begin AFP synthesis. Electron microscopic study showed that each part of the embryoid bodies had some characteristic structures. Most striking features found in the cytodifferentiation of the embryoid bodies were noticed in some special differentiation of plasma membrane and existence of surface coat. Desmosomes were found in endodermal cells and yolk sac cells. Ectodermal cells were attached to each other by zonulae occludentes and adhaerentes. Microvilli were found in ectodermal cells and yolk sac cells. Two different kinds of surface coat were found in mesodermal cells and lining cells of yolk sac cavity: thin‐layered deposit of electron‐dense material covering the plasma membrane facing intercellular space of mesodermal cells and endodermal cells, and thick‐layered deposit of electron‐dense material which covered the plasma membrane facing yolk sac cavity of endodermal cells and yolk sac cells. Presence of similar characteristic material in RER of yolk sac cells led us to speculate that thick deposit was synthesized by yolk sac cells and secreted into yolk sac cavity. Combined with immunoperoxidase study by light microscopy, we assume that this thick‐layered deposit has some close relation to AFP.

Expression of human placenta alkaline phosphatase in placenta during pregnancy

To clarify the expression of PLAP during the course of pregnancy, the amount of PLAP mRNA and its activity in normal placental villi were measured. Both PLAP and its mRNA were found in placentae of as early as 7 weeks of gestation, and they continued to increase throughout pregnancy. But they showed different patterns of increase. The amount of PLAP mRNA began to increase dramatically around 13th week and probably continued to increase gradually until term. PLAP activity per gram of villi showed a gradual increase from around 13th week and a marked increase was observed after about 20th week. PLAP levels in sera from pregnant women were also measured, and they showed a pattern of increase imilar to that of PLAP activity per gram of villi. The continuous increase in the expression of PLAP throughout pregnancy suggests that PLAP may play a role in feto-maternal metabolism and placental differentiation.

Selective suppression of human papilloma virus type 18 mRNA level in HeLa cells by interferon

We have studied the effect of IFN on the transcription of integrated HPV 18 DNA in HeLa cells. We found that the amount of cytoplasmic HPV 18 mRNA was markedly reduced in HeLa cells treated with 10(3) IU/ml of IFN alpha or gamma, and that the inhibitory effect was dose dependent and was detectable by 12h after the addition of IFN. Furthermore, northern blot analysis indicated that IFN remarkably reduced 3.4 kb mRNA species of HPV 18 transcripts in HeLa cells. In contrast, the level of beta-actin mRNA was found to increase in IFN treated cells. The results suggest that IFN alpha and gamma selectively inhibited HPV 18 gene expression at the level of transcription.

Suppression of gelatinase production with decreased invasiveness of choriocarcinoma cells by human recombinant interferon beta

OBJECTIVE Choriocarcinoma is a highly invasive gynecologic tumor, and hematogenous metastases frequently develop. To establish a molecular basis for antiinvasion therapy of choriocarcinoma, we examined the effects of human recombinant interferons on gelatinase production and invasion by choriocarcinoma cells. STUDY DESIGN Using five choriocarcinoma cell lines, we measured gelatinase activity by gelatin zymography. The effects of recombinant interferons (rIFN-alpha, rIFN-beta, and rIFN-gamma) were then analyzed by Western blot analysis and chemoinvasion assay. RESULTS High levels of 72 kd gelatinase activity were detected in the highly invasive choriocarcinoma cell lines, two of which also contained an active form of 72 kd gelatinase with an apparent molecular mass of 68 kd. Gelatinase production was decreased by incubation with rIFN-beta. In the chemoinvasion assay, only rIFN-beta had an inhibitory effect on the invasiveness of tumor cells without a cytotoxic effect. CONCLUSION Choriocarcinoma cells showed high 72 kd gelatinase activity, which suggested a role for the enzyme in vascular metastasis. Studies on the use of rIFN-beta to inhibit metastasis of choriocarcinoma via suppression of gelatinase production are warranted.

Effects of maternal depressive symptomatology during pregnancy and the postpartum period on infant-mother attachment

Postnatal depression has demonstrated long‐term consequences on child cognitive and emotional development; however, the link between maternal and child pathology has not been clearly identified. We conducted a prospective study using self‐rating questionnaires to clarify the association between bonding disorder and maternal mood during pregnancy and after childbirth.

Prospective study of maternal depressive symptomatology among Japanese women.

BACKGROUND The primary objective of this study was to analyze the pattern of depressive moods related to pregnancy and postpartum in a dataset collected prospectively. A secondary objective was to assess the association between (1) low moods during pregnancy and postpartum depressive symptoms, and (2) maternity blues and postpartum depressive symptom. METHOD Three hundred eighty-seven women completed self-administered questionnaires. The participants were asked to respond to Steins Maternity Blues Scale (Steins Scale) on five consecutive days after delivery and to the Edinburgh Postnatal Depression Scale (EPDS) during both pregnancy and postpartum. RESULTS 32.0% of the women were identified as having a score of more than 9 on EPDS during pregnancy and postpartum. 21.6% of the women scored above the Steins Scale cut-off point for at least 1 day during the 5-day period following delivery. The odds ratio (95% CI) for postpartum low mood if the women experienced low mood during pregnancy was 4.46 (2.48-8.04), while the odds ratio for postpartum depressive symptoms if the women experienced symptoms of maternity blues was 5.48 (2.74-10.98). In logistic regression analysis, the number of days in which women scored over the cut-off point by Steins Scale proved to be the more significant predictor of scoring over the EPDS cutoff (8/9) [OR (95% CI)=2.74 (1.89-3.96)]. CONCLUSION The rate of maternity blues in our findings was similar to the rates previously reported in Japan, but lower than the rates observed in Western countries. Furthermore, our longitudinal study confirms the likelihood of subsequent postpartum depressive symptoms if low moods during pregnancy and/or maternity blues are present.

Identification of the pregnancy responsible for gestational trophoblastic disease by DNA analysis

In three cases of choriocarcinoma, genetic loci including a variable number of tandem repeat regions were amplified by the polymerase chain reaction method on DNA from three established cell lines and from lymphocytes of patients and their husbands to identify the responsible pregnancy. Case 1, from whom NaUCC-3 was derived, had only one full-term fetal death. Case 2, from whom NaUCC-4 was derived, had one normal delivery followed by one complete molar delivery and one normal delivery. Case 3, from whom NaUCC-2 was derived, had one normal delivery followed by one complete molar delivery. In case 1, NaUCC-3 was found to be of parental origin and derived from the pregnancy with full-term fetal death. In cases 2 and 3, NaUCC-4 and NaUCC-2 were of probable androgenetic origin and were derived from the pregnancy with complete hydatidiform mole. We also conducted the restriction fragment length polymorphism method using case 1 samples, and it confirmed the results based on the polymerase chain reaction method product patterns. All nine cases of hydatidiform mole and three cases of invasive mole were of androgenetic origin. The polymerase chain reaction method thus makes it possible to identify easily the pregnancy responsible for choriocarcinoma using only a few specimens without isotopes.

Relationship between social support during pregnancy and postpartum depressive state: a prospective cohort study

Although the association between social support and postpartum depression has been previously investigated, its causal relationship remains unclear. Therefore, we examined prospectively whether social support during pregnancy affected postpartum depression. Social support and depressive symptoms were assessed by Japanese version of Social Support Questionnaire (J-SSQ) and Edinburgh Postnatal Depression Scale (EPDS), among 877 pregnant women in early pregnancy and at one month postpartum. First, J-SSQ was standardized among peripartum women. The J-SSQ was found to have a two-factor structure, with Number and Satisfaction subscales, by exploratory and confirmatory factor analyses. Analysis of covariance was performed to examine how EPDS and J-SSQ scores during pregnancy affected the EPDS score at postpartum. Significant associations were found between postpartum EPDS score and both EPDS and total scores on the Number subscales during pregnancy (β = 0.488 and -0.054, ps < 0.001). Specifically, this negative correlation was stronger in depressive than non-depressive groups. Meanwhile, total score on Satisfaction subscales was not significantly associated with postpartum EPDS score. These results suggest that having a larger number of supportive persons during pregnancy helps protect against postpartum depression, and that this effect is greater in depressive than non-depressive pregnant women. This finding is expected to be vitally important in preventive interventions.