Elevated amniotic fluid leptin levels in pregnant women who are destined to develop preeclampsia.

OBJECTIVE: To analyze whether leptin levels of the amniotic fluid elevate during early pregnancy in women destined to develop preeclampsia and to evaluate the relationship between amniotic fluid leptin levels and gestational age, maternal body mass index, and fetal sex. STUDY DESIGN: Leptin levels of the amniotic fluid were compared in two groups of women, preeclamptic (n = 20) and normotensive pregnant (n = 40), matched for fetal sex, maternal body mass index at sampling, gravidity and fetal gestational age at sampling. Furthermore, amniotic leptin levels in 400 normotensive pregnant women were analyzed for their correlation with gestational age, maternal body mass index, and fetal sex. RESULTS: Median leptin concentrations were significantly higher (p < 0.001) in the women with preeclampsia (7.3+/-0.7 ng/ml) than in the normotensive pregnant women (4.1 +/- 0.3 ng/ml), independent of fetal sex. The leptin levels in the amniotic fluid decreased with advanced gestational age (r = 0.24, p < 0.001). Amniotic fluid leptin levels in the pregnant women carrying a female fetus (5.6+/-0.3ng/ml) were significantly higher than those carrying a male fetus (4.7+/-0.2 ng/ml) (p = 0.004). CONCLUSION: Higher amniotic fluid leptin levels were observed in the preeclamptic pregnant women, and they decreased as gestational age advanced. Furthermore, the women with a female fetus were noted to have higher amniotic fluid leptin levels.

The fractionated Toona sinensis leaf extract induces apoptosis of human ovarian cancer cells and inhibits tumor growth in a murine xenograft model.

OBJECTIVE: Aqueous extract from the leaves of Toona sinensis Roem. has been shown to have an anti-proliferative effect on human lung cancer cells. In this study, we analyzed the anti-cancer activity/effect of different extraction fractions of the extract from T. sinensis leaves on ovarian cancer cells. METHODS: Cell viability was determined by XTT cell proliferation assay and cell survival assay. Apoptotic effect was detected by morphological analysis and immunoblotting. Cell cycle effect was evaluated by flow cytometry analysis and immunoblotting. In vivo therapeutic effect was evaluated by the subcutaneous inoculation of SKOV3 cells in nude mice (Foxnlnu/Foxnlnu) model. RESULTS: TSL2 of T. sinensis was more cytotoxic than other fractions and exhibited selectivity for ovarian cancer cell lines. TSL2 arrested SKOV3 ovarian cancer cells at the G2/M phase and induced cancer cells go through apoptotic pathway. Ex vivo xenograft study of nude mice showed that intraperitoneal injection of TSL2 was able to suppress the proliferation of ovarian cancer cells without significant nephrotoxicity, liver toxicity, or bone marrow suppression.

Serum adiponectin and leptin levels in Taiwanese breast cancer patients.

The role of two adipocytokines, adiponectin and leptin, in Taiwanese breast cancer patients remains to be determined. In this study, we analyzed the correlations between the serum levels of adiponectin and leptin and the various clinicopathological parameters in 100 newly diagnosed, histologically confirmed breast cancer patients and 100 controls. We found serum levels were decreased significantly for adiponectin in the breast cancer patients, in comparison to controls (Student t-test, P=0.003), while serum levels were increased significantly for leptin in the breast cancer patients in comparison to controls (Student t-test, P=0.025). Leptin/adiponectin (L/A ratio) were increased significantly in the breast cancer patients, in comparison to controls (Student t-test, P=0.009). Among the clinicopathological parameters, estrogen receptor, progesterone receptor, HER2/neu, lymph node metastasis, tumor stage, and tumor grade all showed no effect on the serum levels of adiponectin and leptin. BMI was negatively and positively correlated to serum adiponectin and leptin levels, respectively (Spearman's correlation, r=-0.333 and 0.323, respectively; P<0.001 for both). Intriguingly, serum L/A ratio disclosed a positive correlation to tumor size (r=0.21, P=0.036). In summary, our results suggest that low serum adiponectin levels and high serum leptin levels are associated with an increased risk for breast cancer. Also, independent of the effect of BMI, the increased serum ratio of L/A may indicate the presence of aggressive breast cancers.

Decreased expression of phosphorylated JNK in breast infiltrating ductal carcinoma is associated with a better overall survival.

Phosphorylation/activation of c-jun NH2-terminal kinase (JNK) has an ambivalent role, pro-proliferation or antiproliferation, in human cancers, which is determined by different cell types and by its crosstalk with other kinases. So far, the role of phosphorylated JNK (p-JNK) in breast cancer is mostly undefined. In this study, we analyzed the expression of p-JNK, as well as p-ERK1/2 and p-38, in the pair of cancer and noncancer breast tissues, by using immunoblotting techniques. These results were further correlated with the clinicopathological characteristics and overall survival. Decreased p-JNK1/2 expression in cancer tissues was observed in 48.5% of breast infiltrating ductal carcinoma (IDC) cases and was correlated significantly with the increased tumor grade and the decreased age at diagnosis (p = 0.030 and 0.029). Interestingly, the Kaplan-Meier survival curve showed that the decreased p-JNK1/2 expression was associated with a better overall survival of IDC (p = 0.004). The expression of p-JNK1/2 was positively correlated with p-p38 (p = 0.002), but not p-ERK1/2. Furthermore, co-expressed p-JNK1/2 and p-p38 was associated with a poor overall survival of IDC (p = 0.007). In conclusion, our results indicate that the aberrant p-JNK1/2 expression and the co-expressed p-JNK1/2 and p-p38 in breast tissues may play a role in the carcinogenesis of breast IDC.

Aberrant serum adiponectin levels in women with uterine leiomyomas.

BACKGROUND: Adiponectin is an adipocyte-secreted hormone. Serum adiponectin levels are inversely correlated with insulin resistance, and low plasma adiponectin levels have been demonstrated in type 2 diabetic patients. However, information on serum adiponectin levels in gynecological disorders is mostly lacking. In this study, we analyzed the possible correlation between serum adiponectin levels and uterine leiomyomas. METHODS: Serum adiponectin levels, determined by radioimmunoassay, were compared in women with uterine leiomyomas (n = 47) and normal controls (n = 46). RESULTS: Serum adiponectin levels in women with uterine leiomyomas (16.4 +/- 0.9 microg/ml) were significantly lower (p < 0.05) than those in the normal controls (19.5 +/- 1.0 microg/ml). Furthermore, there was an inverse correlation between serum adiponectin levels and body mass index, in both women with leiomyomas and normal controls. CONCLUSIONS: Serum adiponectin levels are significantly decreased in myomatous patients.

Elevated amniotic fluid leptin levels in early second trimester are associated with earlier delivery and lower birthweight in twin pregnancy.

OBJECTIVE: To explore the possibility of using early second trimester amniotic fluid leptin levels as a predictor of pregnancy outcome in twin pregnancy. STUDY DESIGN: Amniotic fluid leptin levels from 18 twin-pregnant women in early second trimester were analyzed for their correlation with gestational age at delivery and fetal birthweight. Leptin levels in 16 amniotic fluid samples collected from small for gestational age (SGA) twin pregnancies were compared with those in 20 amniotic fluid samples collected from non-SGA twin pregnancies. RESULTS: A significant correlation was observed between amniotic fluid leptin levels and gestational age at delivery (r = 0.71, p < 0.001) as well as fetal birthweight (r = 0.72, p < 0.001). There was also a significant correlation between gestational age at delivery and fetal birthweight (r = 0.92, p < 0.001). The average gestational age at delivery was 30.4 +/- 1.4 weeks in the SGA group, with a mean birthweight of 1552 +/- 200 g at delivery. For the non-SGA group, the values were 37.3 +/- 0.5 weeks and 2759 +/- 115 g ( p < 0.001), respectively. Amniotic fluid leptin levels were found to be significantly higher ( p < 0.001) for women in the SGA group (11.4 +/- 1.5 ng/mL) than for those in the non-SGA group (5.4 +/- 0.5 ng/mL). CONCLUSION: Higher amniotic fluid leptin levels in early second trimester were associated with both lower gestational age at delivery and lower birthweight. Our results suggest that amniotic fluid leptin levels in early second trimester may be a good marker for the prediction of perinatal complications in twin pregnancy.

Aberrant expression and possible involvement of the leptin receptor in bladder cancer.

OBJECTIVES: To explore the expression patterns and possible involvement of leptin and its receptor in the pathogenesis of urinary bladder cancer, with a focus on transitional cell carcinoma. METHODS: Using reverse transcription-polymerase chain reaction, immunoblotting, and immunohistochemistry techniques, we correlated the expression patterns of leptin and its receptor with the occurrence of transitional cell carcinoma. We also applied transient transfection followed by BrdU labeling and immunofluorescent staining to address the effect of the leptin receptor on bladder cancer cell growth. RESULTS: Although leptin was not detected in the bladder tissue specimens, a decreased expression of the leptin receptor was observed in most cancer tissue specimens we analyzed. Furthermore, the forced expression of the leptin receptor in T24 bladder cancer cells prevented them from entering the S phase. CONCLUSIONS: Our data demonstrated for the first time that the leptin receptor is aberrantly expressed in bladder cancer tissue and is possibly involved in the carcinogenesis of bladder cancer.

Correlations between umbilical and maternal serum adiponectin levels and neonatal birthweights.

OBJECTIVE: To measure adiponectin levels in maternal serum and umbilical cord serum at delivery, and examine whether or not there are correlations between adiponectin levels and neonatal birthweights, maternal body weights and body mass indexes. STUDY DESIGN: The study included 84 healthy mothers who had given birth to healthy neonates. Adiponectin levels in maternal serum and umbilical cord serum were determined by radioimmunoassay and compared. RESULTS: The ranges of adiponectin levels for umbilical cord serum and maternal serum were 22.7-78.4 microg/ml and 4.0-43.3 microg/ml, respectively. Umbilical serum adiponectin levels (46.9 +/- 1.2 microg/ml) were significantly higher than maternal serum adiponectin levels (16.1 +/- 0.8 micro g/ml) (p < 0.001). No correlation was found between the adiponectin levels in maternal serum and those in umbilical cord serum (r = 0.158, p = 0.151). Umbilical serum adiponectin levels were significantly correlated with both neonatal birthweights (r = 0.454, p < 0.001) and gestational ages at birth (r = 0.295, p = 0.006), but not with maternal serum adiponectin levels. Maternal serum adiponectin levels were only negatively correlated to maternal weights and body mass index at delivery (r = 0.288, p = 0.008; r = 0.372, p < 0.001). CONCLUSION: The levels of adiponectin were higher in umbilical cord serum than in maternal serum. Moreover, the adiponectin levels in umbilical cord serum were found to correlate positively with neonatal birthweights. Therefore, fetal adiponectin, not maternal serum adiponectin, may be involved in fetal development during late pregnancy.

Aberrant expression and possible involvement of the leptin receptor in endometrial cancer.

OBJECTIVE: Leptin and its receptor are the key players in the regulation of energy balance and body weight control. However, their roles in gynecological malignancies are mostly unclear. In this study, we analyzed the expression and possible involvement of leptin and the leptin receptor in the pathogenesis of endometrial cancer. METHODS: Radioimmunoassay was performed to analyze the serum leptin levels in the endometrial cancer patients, while RT-PCR, immunoblotting, and immunohistochemistry techniques were applied to study the expression of leptin receptor in the endometrioid-type endometrial cancer tissues. Furthermore, BrdU labeling followed by immunofluorescent analysis was used to analyze the effect of leptin receptor overexpression on endometrial cancer cell proliferation. RESULTS: Serum leptin levels are elevated in endometrial cancer patients, but show no significant difference to those of normal controls when normalized by body mass index. On the other hand, lower expression levels of leptin receptor short form (Ob-Ra) were observed in most endometrial cancer tissues, especially in the poorly differentiated ones, and the forced expression of Ob-Ra in RL95-2 endometrial cancer cells prevented them from entering the S-phase. CONCLUSION: In summary, our data demonstrates for the first time that the leptin receptor is aberrantly expressed in endometrial cancer tissues and is possibly involved in the pathogenesis of endometrial cancer.

Neocarzinostatin-induced Rad51 nuclear focus formation is cell cycle regulated and aberrant in AT cells.

DNA double-stranded breaks are the most detrimental form of DNA damage and, if not repaired properly, may lead to an accumulation of chromosomal aberrations and eventually tumorigenesis. Proteins of the Rad51/Rad52 epitasis group are crucial for the recombinational repair of DNA double-stranded breaks, whereas the Rad50/NBS1/Mre11 nuclease complex is involved in both the recombinational and the end-joining repair of DNA double-stranded breaks. Herein, we demonstrate that the chemotherapeutic enediyne antibiotic neocarzinostatin induced Rad51, but not NBS1, nuclear focus formation in a cell- cycle-dependent manner. Furthermore, neocarzinostatin-induced Rad51 foci formation revealed a slower kinetic change in AT cells, but not in wild-type or NBS cells. In summary, our results suggest that neocarzinostatin induces Rad51 focus formation through an ATM- and cell-cycle-dependent, but NBS1-independent, pathway.

Amniotic fluid and maternal serum leptin levels in pregnant women who subsequently develop preeclampsia.

OBJECTIVES: To study the correlation between amniotic fluid leptin levels and maternal serum leptin levels during the early second trimester, and to determine whether the ratios of amniotic fluid leptin levels to maternal serum leptin levels are elevated in pregnant women who subsequently develop preeclampsia. STUDY DESIGN: Samples from 120 pregnant women were included in this prospective study, of which 20 were from pregnant women who subsequently developed preeclampsia and 100 were from normal pregnant women. Both the amniotic fluid and the maternal serum leptin levels were ascertained by radioimmunoassay (RIA). RESULTS: A strong correlation between amniotic fluid leptin levels and maternal serum leptin levels was observed in both preeclamptic and normal pregnant women. In addition, the ratios of amniotic fluid leptin levels to maternal serum leptin levels were positively correlated to amniotic fluid leptin levels, but negatively correlated to maternal serum leptin levels. Furthermore, the ratios of amniotic fluid leptin levels to maternal serum leptin levels in preeclamptic women were significantly higher than those in normal pregnant women. CONCLUSIONS: Amniotic fluid leptin levels correlated with maternal serum leptin levels during the early second trimester. The ratios of amniotic fluid leptin levels to maternal serum leptin levels were elevated in preeclamptic women. However, the maternal serum leptin levels themselves showed no such elevation. Therefore, this elevated ratio may be a marker at the early stage of pregnancy in preeclamptic women.

Decreased serum leptin levels in women with uterine leiomyomas.

OBJECTIVE: To analyze the possible involvement of leptin in uterine leiomyomas. STUDY DESIGN: Serum leptin levels, determined by radioimmunoassay, were compared in myomatic (n = 50) and the normal (n = 50) women. RESULTS: A significant correlation was found between serum leptin levels and body mass index in both the myomatic women (r = 0.76, p < 0.001) and the normal women (r = 0.56, p < 0.001). Serum leptin levels in the myomatic women (9.3 +/- 0.6 ng/mL) were significantly lower (p < 0.001) than those in the normal women (13.6 +/- 1.2 ng/mL). In addition, the ratios of serum leptin levels/body mass index in the myomatic women (0.38 +/- 0.02) were significantly lower than those in the normal women (0.57 +/- 0.04) (p < 0.001). A significant correlation was found between the ratios of serum leptin levels/body mass index and body mass index (r = 0.59, p < 0.001) in the normal women, but not in the myomatic women (r = 0.27, p = 0.061). CONCLUSION: The lower plasma leptin levels observed in the women with myomas were independent of body mass index, and unlike the normal women there was no significant up-regulation of leptin production in response to increased adiposity.