Effects of ER-resident and secreted AGR2 on cell proliferation, migration, invasion, and survival in PANC-1 pancreatic cancer cells.

BACKGROUND: Anterior gradient-2 (AGR2) is a proto-oncogene involved in tumorigenesis and cancer progression. AGR2, predominantly localized in the endoplasmic reticulum (ER), is also a secreted protein detected in the extracellular compartment in multiple cancers. However, the biological functions of intracellular and extracellular AGR2 remain to be elucidated. METHODS: Based on the biochemical structure of AGR2 protein, PANC-1 pancreatic cancer cells stably expressing ER-resident or secreted AGR2 were generated by a lentivirus-mediated stable overexpression system. The capacities of cell proliferation, migration, invasion and survival were assessed in PANC-1 stable cells. Moreover, EGFR expression and activation were determined to explore the possible mechanism of AGR2 roles in pancreatic cancer tumorigenesis. RESULTS: It was discovered that secreted AGR2, but not ER-resident AGR2, promotes cell proliferation, migration and invasion of PANC-1 cells. Moreover, the data indicated that both the ER-resident and the secreted AGR2 enhance the survival capacity of PANC-1 cells after tunicamycin-induced ER stress and gemcitabine treatment. However, EGFR expression and activation were not found to be involved in AGR2-dependent oncogenic phenotypes in PANC-1 cells. CONCLUSIONS: Secreted AGR2 is predominantly involved in cell proliferation, migration and invasion in PANC-1 pancreatic cancer cells. Both secreted and ER-resident AGR2 contribute to the survival of PANC-1 cells under the challenging conditions. These findings provide insight into how different localizations of AGR2 have contributed to pancreatic cancer growth, metastasis, and drug sensitivity.

Prenatal Diagnosis and Pregnancy Outcome Analysis of Polyhydramnios.

The aim of the study was to investigate the etiology and pregnancy outcomes in mothers with polyhydramnios through prenatal diagnosis and pregnancy outcome analysis of pregnant women with polyhydramnios. One hundred and thirty women were enrolled. Fifty pregnant women with polyhydramnios were categorized as the case group, and 80 pregnant women with normal amniotic fluid were categorized as the control group. The causes of polyhydramnios and the pregnancy outcomes were analyzed. Two cases had chromosomal abnormalities, seven had severe α-thalassemia, 15 had fetal anomalies, four had maternal-fetal diseases and 22 had unexplained idiopathic polyhydramnios. Significantly, higher occurrences of cesarean section, preterm birth, fetal anomaly, fetal distress, fetal macrosomia and female fetuses occurred in patients with polyhydramnios than in patients without polyhydramnios. Polyhydramnios is associated with a higher occurrence of adverse perinatal outcomes. Intensive monitoring of the maternal-fetal condition and prenatal diagnosis is important in patients with polyhydramnios.

Maternal IgG Anti-A and Anti-B Titer Levels Screening in Predicting ABO Hemolytic Disease of the Newborn: A Meta-Analysis.

UNLABELLED: Maternal IgG anti-A/B titers have been considered as a susceptible factor to the risk of ABO hemolytic disease in newborn (ABO-HDN). However, the results remain controversial. This meta-analysis aimed to estimate the association between maternal IgG anti-A/B titers and the risk of ABO-HDN. METHODS: Trials on the relationship between maternal IgG anti-A/B titers and the risk of ABO-HDN were collected by searching Embase, PubMed, and Cochrane Central Register of Controlled Trials (CENTRAL) electronic databases. The inclusion criteria were maternal IgG anti-A/B titers screening and the evaluation of clinical outcomes in relation to ABO-HDN. Stata 12.0 was used to analyze the data. RESULTS: A total of 23 trials were eligible for inclusion, of which four trials with 5,246 participants were suitable for this meta-analysis. Meta-analysis results suggested that maternal IgG anti-A/B titers were significantly associated with the risk of ABO-HDN [OR = 2.86, 95% CI = 2.50-3.28; OR = 4.67, 95% CI = 3.92-5.55; OR = 1.61, 95% CI = 1.36-1.91 in titers (128 to 256) vs. titers (64 or lower), titers (512 or higher) vs. titers (64 or lower), and titers (512 or higher) vs. titers (128-256), respectively]. CONCLUSIONS: Our meta-analysis suggests that maternal IgG anti-A/B titers are significantly associated with the risk of ABO-HDN. They contribute to the prediction of risk of ABO-HDN, in addition to the need for invasive treatment for antibody titers ≥512.

Expression of FK506-binding protein 52 (FKBP52) in chorionic villi with early recurrent spontaneous abortion.

OBJECTIVE: To investigate the mRNA and protein expression of FK506-binding protein 52 (FKBP52) in the chorionic villi of patients with recurrent spontaneous abortion (RSA) and normal women during early pregnancy. METHODS: Fresh chorionic villus tissues were collected from 60 subjects. A total of 30 patients with a history of RSA were enrolled into the RSA group and 30 normal pregnant women were enrolled into the control group. The FKBP52 mRNA expression levels in chorionic villi of the RSA patients and healthy controls were measured via semiquantitative RT-PCR. The protein distribution and expression levels of FKBP52 in chorionic villi were analyzed through immunohistochemistry (IHC). The correlation between FKBP52 expression and RSA was analyzed. RESULTS: We demonstrated that FKBP52 mRNA is expressed in chorionic villi samples of normal pregnancy and RSA. RSA patients exhibited significantly lower FKBP52 gene expression levels compared with those in normal pregnancies (p < 0.05). FKBP52 immunoreactivity in chorionic villi was mainly observed in trophoblast cell cytoplasm. The FKBP52 protein expression levels in the chorionic villi of RSA patients was significantly lower than in normal women during pregnancy (p < 0.05). CONCLUSIONS: FKBP52 protein levels were decreased in the chorionic villi of RSA patients, which indicate that the decrease in FKBP52 may be associated with RSA. The low FKBP52 mRNA expression level, which is consistent with the IHC result, may affect embryonic development and even lead to abortion. FKBP52 may be involved in the pathogenesis of RSA and new therapies that increase the FKBP52 expression may help treat RSA.

Association study between CYP17 gene polymorphism and endometriosis risk: a meta-analysis.

The cytochrome P450 subfamily 17 (CYP17) gene T > C polymorphism is associated with endometriosis risk. However, studies on the association between the genotyping of MspA1 polymorphism in the 5'-untranslated region of the CYP17 gene and endometriosis risk have reported controversial results. The aim of the present study was to obtain a more precise estimate of the relationship of CYP17 gene polymorphism with endometriosis risk. Relevant articles published up to April 2014 were obtained from Pubmed, Embase, and Cochrane Central electronic databases. Case-control studies about the association between CYP17 gene polymorphisms and endometriosis were selected. Eligible data were extracted by two independent reviewers. The strength of the association between CYP17 and endometriosis was assessed by pooled odds ratios (OR) with 95% confidence intervals (CI). Eligible case-control studies involving 1000 cases and 1167 controls were analyzed from 280 studies. The pooled results showed no association between the CYP17 gene T > C polymorphism and endometriosis risk in the overall population (CC vs TT: OR = 0.92, 95% CI = 0.52-1.61, P = 0.762; TC vs TT: OR = 1.01, 95% CI = 0.72-1.42, P = 0.949; dominant model: OR = 0.94, 95% CI = 0.64-1.39, P = 0.763; recessive model: OR = 0.93, 95% CI = 0.64-1.35, P = 0.712). In the subgroup analysis based on ethnicity, no significant association was found in Asians, Caucasians and mixed population under a recessive model (Asians: OR = 0.76, 95% CI = 0.53-1.07, P = 0.118; Caucasians: OR = 2.47, 95% CI = 0.45-13.66, P = 0.300; mixed population: OR = 1.40, 95% CI = 0.65-3.02, P = 0.712). In conclusion, the meta-analysis suggested that the CYP17 gene polymorphism was not associated with endometriosis risk. Considering the limited sample size and ethnicity included in our meta-analysis, an updated meta-analysis needs to be conducted when larger and more well-designed studies are published.

Risk of chromosomal abnormalities in early spontaneous abortion after assisted reproductive technology: a meta-analysis.

BACKGROUND: Studies on the risk of chromosomal abnormalities in early spontaneous abortion after assisted reproductive technology (ART) are relatively controversial and insufficient. Thus, to obtain a more precise evaluation of the risk of embryonic chromosomal abnormalities in first-trimester miscarriage after ART, we performed a meta-analysis of all available case-control studies relating to the cytogenetic analysis of chromosomal abnormalities in first-trimester miscarriage after ART. METHODS: Literature search in the electronic databases MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) based on the established strategy. Meta-regression, subgroup analysis, and Galbraith plots were conducted to explore the sources of heterogeneity. RESULTS: A total of 15 studies with 1,896 cases and 1,186 controls relevant to the risk of chromosomal abnormalities in first- trimester miscarriage after ART, and 8 studies with 601 cases and 602 controls evaluating frequency of chromosome anomaly for maternal age≥35 versus <35 were eligible for the meta-analysis. No statistical difference was found in risk of chromosomally abnormal miscarriage compared to natural conception and the different types of ART utilized, whereas the risk of fetal aneuploidy significantly increased with maternal age≥35 (OR 2.88, 95% CI: 1.74-4.77). CONCLUSIONS: ART treatment does not present an increased risk for chromosomal abnormalities occurring in a first trimester miscarriage, but incidence of fetal aneuploidy could increase significantly with advancing maternal age.

Not every subseptate uterus requires surgical correction to reduce poor reproductive outcome.

OBJECTIVE: To evaluate whether hysteroscopic septoplasty should be performed in all women diagnosed with subseptate uterus. METHODS: In a prospective study, 138 patients diagnosed with subseptate uterus at the First Affiliated Hospital of Guangxi Medical University, Nanning, China, were enrolled between January 1, 2006, and March 1, 2011, and reproductive outcomes were compared among women who did and those who did not undergo hysteroscopic resection. Women were divided in 2 groups: group A comprised women with a history of recurrent spontaneous abortion (RSA), and was subdivided into control (A1) and surgery (A2) groups; group B comprised women with no history of poor reproductive outcomes, and was subdivided into control (B1) and surgery (B2) groups. RESULTS: The rates of pregnancy and term delivery were higher in group A2 than in group A1 (P<0.05). The incidence of RSA and preterm delivery was higher in group A1 than in group A2 (P<0.05). There was no difference in pregnancy rate, incidence of RSA, or preterm or term delivery between group B1 and group B2. CONCLUSION: Hysteroscopic septoplasty significantly improved pregnancy outcomes in women with a history of RSA, but did not influence reproductive outcomes in women with no history of poor pregnancy outcomes.

[Prenatal diagnosis of Thailand deletion of alpha-thalassemia 1].

OBJECTIVE: To conduct prenatal diagnosis on the couples carrying Thailand deletion (--THAI) alpha-thalassemia 1 and at high risk of having fetus with alpha-thalassemia. METHODS: Genotypes of couples and fetuses were analyzed by PCR and DNA sequencing. RESULTS: Four pregnant women were patients with Hb H diseases of --THAI compounding with alpha-thalassemia 2, while their husbands were heterozygote of the Southeast Asian type alpha-thalassemia 1 (--SEA). Another 5 families, either husbands or wives were heterozygote of --THAI or --SEA. The genotypes of their fetuses were as follows: 2 cases with Hb Bart's hydrops fetalis syndrome, 1 Hb H disease, 4 alpha-thalassemia heterozygote and 2 normal. The DNA sequencing approved the PCR results. CONCLUSION: The study on prenatal diagnosis of Thailand deletion alpha-thalassemia 1 is of importance to the genetic counseling and prenatal diagnosis of alpha-thalassemia.