Cardiac tamponade during pregnancy due to primary lung cancer: A case report.

We report a rare case of cardiac tamponade caused by lung cancer in a pregnant woman. A 32-year-old multiparous pregnant woman was admitted to the hospital at 15 weeks of gestation with a persistent cough and dyspnea. Transthoracic echocardiography revealed a pericardial effusion with evidence of tamponade physiology. Computed tomography (CT) revealed a massive pericardial effusion and a left lung tumor. Pericardial tamponade was successfully treated using pericardiocentesis. She was diagnosed with lung adenocarcinoma stage IVB based on bronchoscopic lung biopsy, which showed adenocarcinoma and CT, which showed brain metastasis. Pregnancy was terminated at 18 weeks of gestation, followed by molecular-targeted therapy with alectinib hydrochloride and whole-brain irradiation. 24 months after treatment initiation the patient is alive without disease progression. Although pericardial tamponade caused by a malignant tumor during pregnancy is a rare and serious life-threatening condition, appropriate diagnosis and prompt treatment can improve maternal prognosis.

Early menopause and a low body mass index are associated with an increased risk of coronary heart disease in Japanese women.

OBJECTIVE: The primary objective was to investigate the association between early menopause and cardiovascular disease (CVD) prevalence in Japanese women. The secondary objective was to ascertain the association with CVD risk factors. METHODS: In this cross-sectional study, 7,239 naturally menopausal women from the Yamagata Cohort Study who completed an annual health visit and questionnaire between 2009 and 2015 were divided into three groups according to their age at menopause (women experiencing menopause at <45, 45-49 y, and ≥ 50 y). The diagnosis of coronary heart disease (CHD) and stroke were made by self-report, while hypertension, hyperlipidemia, and diabetes mellitus, were diagnosed by vital signs and laboratory parameters. Logistic regression analysis was used to estimate the associations between age at menopause and CVD prevalence and CVD risk factors. RESULTS: A total of 354 (4.9%) and 156 (2.2%) women reported a history of CHD and stroke, respectively. Women experiencing menopause at <45 years had a higher prevalence of CHD than those experiencing menopause at ≥50 years (OR 1.77, 95% CI 1.07-2.90; P = 0.023). Stroke, hypertension, diabetes mellitus, and hyperlipidemia were equally prevalent among the three groups. Significant interactions were observed between age at menopause and body mass index (BMI) (P = 0.025) and parity (P = 0.025). Among those with a BMI < 18.5 or parity ≥2, women experiencing menopause at <45 years had a significantly higher prevalence of CHD than those experiencing menopause at ≥50 years. CONCLUSION: Early menopause and low BMI were associated with CHD in Japanese women.

The Change of Oxidative Stress in Maternal Blood During Pregnancy.

Oxidative stress (OS) is a state in which the oxidative capacity exceeds the antioxidant capacity in vivo. OS is associated with various perinatal diseases. There have been few reports about OS during pregnancy, such as OS changes that occur during gestation, normal maternal OS dynamics, and OS levels in umbilical cord blood. We here examined the oxidative and antioxidant capacity in maternal blood as well as in umbilical cord vein blood during normal pregnancy. Pregnant women managed from early pregnancy to the postpartum period in our hospital, from April 2018 to March 2019, were included. We obtained maternal blood at 12, 24, and 36 weeks of gestation and obtained umbilical cord blood at delivery. The OS (derivatives of reactive oxygen metabolites [d-ROMs]) and antioxidant capacity (biological antioxidant potential [BAP]) of blood samples were measured. D-ROMs and BAP were compared across gestational weeks. Moreover, d-ROMs and BAP were compared between mothers with and without disease. We analyzed 100 pregnancies (651 specimens). Eleven patients developed hypertensive disorder of pregnancy (HDP)/preeclampsia (PE). The median maternal age was 35 years, and the median gestational age at delivery was 39 weeks. Thirty-one women had undergone fertility treatments. D-ROM values were significantly higher and BAP values were significantly lower in mid- and late pregnancy than in early pregnancy. D-ROM and BAP showed no significant differences between HDP/PE and non-hypertensive groups. During pregnancy, maternal OS increases, and antioxidant capacity decreases with advancing gestational age.

Oxidative Stress in the Visceral Fat Is Elevated in Postmenopausal Women with Gynecologic Cancer.

OBJECTIVES: This study aimed to evaluate differences in oxidative stress of visceral fat between premenopausal and postmenopausal women and clarify the antioxidant effect of estrogen on adipocytes. MATERIALS AND METHODS: Abdominal subcutaneous and omental visceral adipose tissues were obtained from 38 patients who underwent gynecological surgery. We measured the sizes of the adipocytes and evaluated the lipid peroxidation levels in the adipose tissues. We investigated whether estrogen inhibited the intracellular reactive oxygen species (ROS) production that was induced by hydrogen peroxide (H2O2) in 3T3-L1 adipocytes. RESULTS: The visceral adipocytes were 1162.4 µm2 and 1881.9 µm2 in premenopausal and postmenopausal women, respectively; hence they were significantly larger in the latter (p < 0.05). The lipid peroxidation levels were 46.7 nmoL/mg protein in premenopausal women and 99.6 nmoL/mg protein in postmenopausal women; hence the lipid peroxidation levels were significantly higher in the latter (p < 0.05). Estradiol (E2) significantly reduced the intracellular ROS levels that were induced by H2O2 in 3T3-L1 adipocytes (p < 0.01). We determined that E2 significantly increased the expression of nuclear factor erythroid 2-related factor 2 (NRF2)-dependent antioxidant genes, heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), and the glutamate-cysteine ligase (GCL) modifier subunit genes, in 3T3-L1 adipocytes (p < 0.01). CONCLUSION: Oxidative stress in the visceral fat is higher in postmenopausal women. The expression of the antioxidant genes HO-1, NQO1, and GCL was upregulated by estrogen in 3T3-L1 adipocytes. Hence, estrogen may act as an antioxidant in the adipose tissues of premenopausal women.

Activation of estrogen receptor α by estradiol and cisplatin induces platinum-resistance in ovarian cancer cells.

Activation of Estrogen receptor (ER) α (α) promotes cell growth and influences the response of cancer cell to chemotherapeutic agents. However, the mechanism by which ERα activation antagonizes cells to chemotherapy-induced cytotoxicity remains unclear. Here, we investigated the effect of cisplatin on ERα activation. In addition, we examined whether down-regulation of ERα modulate cisplatin-mediated cytotoxicity using 2 human ovarian cancer cells (Caov-3 and Ovcar-3) transduced with ERα short hairpin RNA (shRNA). The proliferation assay showed that 17ß-estradiol (E2) induced cell proliferation via activation of Akt and extracellular signal-regulated kinase (ERK) cascades, while shRNA mediated downregulation of ERα inhibited the cell proliferation. Immunoblot analysis revealed that cisplatin induced the phosphorylation of ERα at serine 118 via ERK cascade. Luciferase assay showed that cisplatin increases transcriptional activity of estrogen-responsive element (ERE). The E2-stimulated ERα activation attenuated cisplatin-induced cytotoxicity. Meanwhile, down-regulation of ERα inhibited E2-induced protective effect on cisplatin toxicity as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Moreover, Pretreatment with E2 followed by cisplatin decreased the expression of cleaved PARP, and increased the expression of anti-apoptotic protein Bcl-2. Collectively, our findings suggest that activation of ERα by E2 and cisplatin can induce platinum-resistance by increasing the expression of anti-apoptotic protein in ovarian cancer cells. Therefore, our findings provide valuable information that ERα might be a promising therapeutic target for platinum-resistant ovarian cancer.

The Wilms' Tumor Gene WT1 - 17AA/- KTS Splice Variant Increases Tumorigenic Activity Through Up-Regulation of Vascular Endothelial Growth Factor in an In Vivo Ovarian Cancer Model.

The Wilms' tumor 1 gene WT1 encodes a zinc transcription factor involved in a variety of cancer-related processes. In this study, we sought to investigate the effects of WT1 splice variants on tumorigenic activity and survival in an in vivo ovarian cancer model. To this end, we established stable ovarian cancer cell lines transduced with lentiviral constructs containing each of the four WT1 splice variants (- 17AA/- KTS, + 17AA/- KTS, - 17AA/+ KTS, and + 17AA/+ KTS). In mice inoculated intraperitoneally with SKOV3ip1 cells expressing WT1 - 17AA/- KTS, disseminated tumor weights and production of ascites were significantly increased compared with those in mice inoculated with cells expressing the control vector. The overall survival in mice inoulated with WT1 - 17AA/- KTS-expressing cells was significantly shorter than that in mice inoculated with control cells (P = .0115). Immunoblot analysis revealed that WT1 - 17AA/- KTS significantly increased the expression of vascular endothelial growth factor (VEGF) compared with the control. Greater numbers of CD31-immunopositive vessels were observed in tumors from mice injected with cells expressing WT1 - 17AA/- KTS than in tumors from control mice. Finally, WT1 - 17AA/- KTS significantly increased tumor microvessel density compared with that in the control (P < .05). Treatment with anti-VEGF antibody (bevacizumab) inhibited tumor growth, dissemination, and ascites production in mice injected with cells expressing WT1 - 17AA/- KTS. The overexpression of WT1 - 17AA/- KTS induced a more aggressive phenotype in ovarian cancer cells through VEGF up-regulation in an in vivo ovarian cancer model. Our findings indicated that WT1 - 17AA/- KTS enhanced tumorigenic activity and could decreased patient survival through up-regulation of VEGF expression in ovarian cancers.

High levels of Wilms' tumor 1 (WT1) expression were associated with aggressive clinical features in ovarian cancer.

AIM: The aim of the present study was to evaluate the correlation between WT1 expression levels and clinical features, to investigate the prognostic value of WT1 expression and to use lentiviral constructs to examine whether overexpression of WT1 affects cell proliferation and invasion in ovarian cancer patients. MATERIALS AND METHODS: Real-time quantitative PCR (qPCR) methods were employed to analyze WT1 expression levels in clinical samples from 63 patients with ovarian cancer. The correlation between the copy number of WT1 mRNA and clinical variables was analyzed. RESULTS: The median copy number of WT1 mRNA was 53.94 (range=2.135-32,257) in all subjects and WT1 expression levels were found significantly increased in patients with a higher stage cancer (p<0.05), lymphnode (p<0.001) and omentum metastasis (p<0.001), as well as ascites production (p<0.05), compared to patients lacking these clinical variables. No significant difference in WT1 expression levels were observed between patients with and without recurrence. The median disease-free survival time in patients with low WT1 expression levels was significantly longer (p=0.038) than that in patients with high WT1 expression. However, overall survival curves showed no statistically significant (p=0.457) differences between patients with high- and low-WT1 expression levels. An in vitro study revealed that WT1 over-expression enhanced cell proliferation and invasion in ovarian cancer cells transduced with lentiviral constructs. CONCLUSION: Using qPCR, we found that high levels of WT1 expression correlated with aggressive clinical features in ovarian cancer. High WT1 expression may impact on median disease-free survival in ovarian cancer.