ABSTRACT: Preeclampsia is associated with elevated levels of proinflammatory cytokines, excess decidual macrophages, and dendritic cells. IL-1β- or TNF-α-stimulated leukocyte-free first trimester decidual cells produced abundant macrophage- and dendritic cell-recruiting chemokines identified in preeclamptic decidua.
The relative potency of IL-1β- or TNF-α-induced first trimester decidual cell-secreted chemokines in chemoattracting macrophages or dendritic cells and the signaling pathways involved in the expression of these chemokines were evaluated.
First trimester decidual cells were treated with estradiol + medroxyprogesterone acetate ± IL-1β or TNF-α. The chemotaxis assay was performed by incubating conditioned medium from first trimester decidual cells with neutralizing antibody for six chemokines. The activation of each signaling pathway was examined by Western blotting, flow cytometry, confocal microscopy, and ELISA with or without kinase and nuclear factor κB (NFκB) inhibitors.
Neutralization of CCL2 and CCL5 significantly reduced chemotaxis of monocyte and dendritic cells up to 50 and 36%, respectively. NFκB and MAPK (MAPK kinase, JUN NH₂-terminal kinase, p38 kinase) pathways were activated by IL-1β or TNF-α in first trimester decidual cells. In IL-1β- or TNF-α-stimulated first trimester decidual cells, NFκB inhibitor suppressed production of all six chemokines; JUN NH₂-terminal kinase inhibitor inhibited secretion of CCL2, CCL4, and CCL5; and MAPK kinase and p38 inhibitor decreased production of CXCL8.
Up-regulation of CCL2 and CCL5 by first trimester decidual cells in response to proinflammatory stimuli may account for the accumulation of macrophages and dendritic cells in preeclamptic decidua. These chemokines and underlying IL-1β- or TNF-α-induced signaling molecules are potential diagnostic and therapeutic targets for preeclampsia.
The Journal of clinical endocrinology and metabolism 06/2011; 96(8):2502-11. · 6.50 Impact Factor
ABSTRACT: Drug resistance is a major concern in the successful treatment of ovarian cancer. In the present study we report a combinational drug regime using arsenic trioxide (ATO) and cisplatin (CDDP) to increase therapeutic potentiality in ovarian cancer cells. ATO-mediated growth inhibition and apoptosis in human suspension ovarian cancer COC1 cells were evaluated by MTT assay and annexin V assay using flow cytometry, respectively. cDNA arrays were performed to screen ATO-mediated gene expression. Treatment of COC1 cells with ATO alone resulted in growth inhibition and apoptosis with a dose-and time-dependent fashion; further cDNA arrays showed that 34 genes (23 up-regulated genes and 11 down-regulated genes) may strongly associate with the antiproliferative and pro-apoptotic effects induced by ATO. Furthermore, Chou-Talalay analysis was used to evaluate the combinational effect of ATO and CDDP as well as dose-reduction index (DRI) in a panel of ovarian cancer cells including CDDP-sensitive and -resistant cell lines. The combination index (CI) analysis indicated that the interaction effect of ATO/CDDP exhibited a wide range of synergism in all the adherent ovarian cancer cells (A2780, IGROV-1, SKOV-3, and R182) as well as 0.93 to 0.69 for IC(50) to IC(90) in suspension COC1 cells where CI < 1, =1, and >1, define synergism, additive effect, and antagonism, respectively. More intriguingly, the combination of ATO and CDDP yielded favorable DRIs ranging from 1.23-fold to 13.51-fold dose reduction. These results suggest that ATO and its combination with CDDP present therapeutic potential for ovarian cancer, and deserve further preclinical and clinical studies.
Cancer Science 09/2009; 100(12):2459-64. · 3.33 Impact Factor
ABSTRACT: ObjectiveTo investigate the clinical symptom, ultrasonographic scan finding, serum CA125 value, histopathological type and treatment
of small ovarian tumor (<5 cm) in postmenopausal women.
MethodsRetrospective analysis was carried out for 52 clinical materials of ovarian tumor cases in women more than one year after
menopausal between Jan 1997 and Dec 2004. The largest diameter of the ovarian mass is less than 5 cm.
ResultsThere were 11 ovarian cancers and 1 borderline ovarian tumor among 52 small ovarian tumors (23.1%). 10 ovarian cancers were
epithelial neoplasms and 2 were sex cord-stromal tumors, and 8 cases were in late stage according to FIGO staging system (33.3%).
Compared with benign tumor, there is no significant difference in the onset age, interval after menopausal and duration of
history. The main clinical feature is abdominal symptoms, such as abdominal pain and distension in the malignant cases. The
patients with benign tumors often showed the ovarian mass during the annual screening or admitted into hospital for other
causes. The ultrasonography finding and serum CA125 level showed much difference between benign and malignant cases. Unilocular
smooth-walled ovarian cysts mostly were found in benign tumor and the CA125 values were always less than 35 U/ml; but the
solid or complex sonographic structures (multilocular, or with a papillary projections on the wall) often indicated a high
risk of cancer, especially there was ascites in the pelvic cavity. Serum CA125 level in many cancer cases was elevated (>35
U/ml), over 300 U/ml in more than half of the patients. Surgery is still the first choice to treat ovarian cancer, and chemotherapy
would be an auxiliary method. Till now, 3 ovarian cancer patients died of complications of cancer and 2 cases had recurrence.
ConclusionSmall ovarian tumor in postmenopausal women has a comparatively low malignant occurrence but more in later stage. Many are
epithelial carcinoma. If there is complex or parenchymal sonographic structure accompanied with a high serum CA125 level,
operation should be considered, while it can be followed up when the ultrasound shows a smooth cyst with normal CA125 value.
Chinese Journal of Cancer Research 08/2006; 18(3):229-234. · 0.18 Impact Factor
ABSTRACT: To evaluate the pregnancy outcome of women with pulmonary hypertension complicating cardiac disease.
Clinical data of 61 cases of pregnant women with pulmonary hypertension from Jan 1996 to Aug 2004 were analyzed and they were divided into three groups: 32 cases of slight group [pulmonary hypertension from 30 mm Hg (1 mm Hg = 0.133 kPa) to 49 mm Hg], 23 cases of moderate group (pulmonary hypertension from 50 mm Hg to 79 mm Hg) and 6 cases of severe group (pulmonary hypertension equal to or higher than 80 mm Hg). The types of heart disease, cardiac functional status (New York heart association, NYHA), gestational weeks of pregnancy termination, mode of delivery and outcomes of infants were compared between the groups.
(1) The occurrence rate of NYHA class III - IV was 5/6 in severe group. The rate of NYHA class I - II was 72% (23/32) in slight group. (2) The rate of moderate and severe pulmonary hypertension was 53% (11/21) and of NYHA class IV 43% (9/21) in rheumatic heart disease. The rate of slight pulmonary hypertension was 97% (35/36) and NYHA class I - II 81% (29/36) in congenital heart disease. (3) The rate of term delivery was 75% (24/32) and the birth weight was 2744 g on average in slight group. The rate of term delivery was 48% (11/23), preterm labor 35% (8/23), abortion 17% (4/23) in moderate group. The rate of term delivery was 1/6, preterm labor occurred in 3 cases, and abortion in 2 cases in severe group. The rates of neonatal complications between the three groups had no significant difference. (4) Caesarean section rate was 79% (48/61) among all patients. (5) Overall maternal mortality was 2% (1/61).
The rate of heart failure increases gradually with the severity of pulmonary hypertension. The severity of pulmonary hypertension in rheumatic heart disease is higher than in congenital heart disease. The rate of maternal mortality and fetal loss increases in pregnant women with pulmonary hypertension complicating cardiac disease. Perinatal morbidity is higher than normal. Cesarean section is more suitable for those women.
Zhonghua fu chan ke za zhi 03/2006; 41(2):99-102.