ABSTRACT
BACKGROUND: We showed previously that breast carcinoma amplified sequence 2 (BCAS2) functions as a negative regulator of p53. We also found that BCAS2 is a potential AR-associated protein. AR is essential for the growth and survival of prostate carcinoma. Therefore we characterised the correlation between BCAS2 and AR. METHODS: Protein interactions were examined by GST pull-down assay and co-immunoprecipitation. Clinical prostate cancer (PCa) specimens were evaluated by immunohistochemical assay. AR transcriptional activity and LNCaP cell growth were assessed by luciferase assay and MTT assay, respectively. RESULTS: BCAS2 expression was significantly increased in PCa. BCAS2 stabilised AR protein through both hormone-dependent and -independent manners. There are at least two mechanisms for BCAS2-mediated AR protein upregulation: One is p53-dependent. The p53 is suppressed by BCAS2 that results in increasing AR mRNA and protein expression. The other is via p53-independent inhibition of proteasome degradation. As BCAS2 can form a complex with AR and HSP90, it may function with HSP90 to stabilise AR protein from being degraded by proteasome. CONCLUSIONS: In this study, we show that BCAS2 is a novel AR-interacting protein and characterise the correlation between BCAS2 and PCa. Thus we propose that BCAS2 could be a diagnostic marker and therapeutic target for PCa.
Subject(s)
Neoplasm Proteins/physiology , Prostatic Neoplasms/metabolism , Receptors, Androgen/genetics , Transcription, Genetic , Benzoquinones/pharmacology , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , HEK293 Cells , HSP90 Heat-Shock Proteins/antagonists & inhibitors , Half-Life , Humans , Inhibitory Concentration 50 , Lactams, Macrocyclic/pharmacology , Male , Neoplasm Grading , Prostatic Neoplasms/pathology , Proteasome Endopeptidase Complex/metabolism , Protein Stability , Proteolysis , Receptors, Androgen/metabolism , Tumor Suppressor Protein p53/metabolismABSTRACT
The efficacy and safety of intracervical placement of laminaria and intravenous prostaglandin E2 (sulprostone) infusion for termination of second-trimester pregnancies with abnormal fetuses was investigated. One hundred and six pregnant women at 13-29 weeks' gestation with fetal anomalies underwent laminaria tent insertion into the cervical canal on admission. The next morning, Sulprostone infusion was started at a rate of 16 microg/h and increased by 16 microg/h every 30 min to induce uterine contractions. Induction-to-abortion time (IAT), success and complete abortion rates, and sulprostone-related side effects were registered. The overall success and complete abortion rates within 24 h were 91.5 and 80.2%, respectively. The mean IAT was 12.1+/-7.6 h. The incidence of nausea and/or vomiting was 17.9%, with 1.7 episodes per case. Diarrhea and fever (9.5%) were not common. Laminaria tent insertion plus sulprostone infusion was an effective and safe regimen for second-trimester termination of pregnancy with live fetuses.
Subject(s)
Abortifacient Agents, Nonsteroidal/administration & dosage , Abortion, Induced , Dinoprostone/analogs & derivatives , Fetus/abnormalities , Laminaria , Adult , Dinoprostone/administration & dosage , Female , Humans , Pregnancy , Pregnancy Trimester, Second , Treatment OutcomeABSTRACT
The association of rare chromosomal rearrangements involving a specific 10q breakpoint with a single umbilical artery (SUA) and sex reversal has never been reported. This report describes the case of a fetus with prenatal ultrasound features of severe intrauterine growth retardation (IUGR), congenital heart disease, and SUA. Fetal blood study revealed de novo deletion of 10q25 and a 46,XY karyotype, while ultrasound demonstrated female genitalia. Based on these findings, sex reversal was diagnosed. Polymerase chain reaction (PCR) amplification revealed the presence of the sex-determining region of the Y (SRY) gene. The pregnancy was terminated at 36 weeks and the newborn weighed 1908 g with marked facial dysmorphism and abnormal genitalia. Because the parents refused autopsy for this case, histopathological examination of gonads was not performed. Breakpoint of the long arm of chromosome 10 may be responsible for sex reversal in the present case and it could thus confirm the concept of autosomal sex reversal proposed in previous reports.
Subject(s)
Chromosomes, Human, Pair 10 , Disorders of Sex Development/genetics , Monosomy , Prenatal Diagnosis , Umbilical Arteries/abnormalities , Abortion, Induced , Adult , Craniofacial Abnormalities/genetics , Female , Fetal Growth Retardation/diagnostic imaging , Fetal Growth Retardation/genetics , Gene Deletion , Heart Defects, Congenital/diagnostic imaging , Humans , Karyotyping , Male , Pregnancy , Ultrasonography, Prenatal , Umbilical Arteries/diagnostic imagingABSTRACT
Beta-thalassemia (thal) is a common single-gene disease worldwide. However, the prevalence of beta-thal and the spectrum of beta-globin gene mutations in Filipinos remain unclear. This study sought to answer these two questions. A total of 2954 apparently healthy Filipinos in Taiwan were recruited for a prevalence study. A complete blood count was done in every subject. Those with microcytosis were studied with hemoglobin (Hb) high-performance liquid chromatography to determine the levels of Hb A2 and Hb F. Twenty-seven subjects had elevated levels of Hb A2 (>4.0%). These 27 suspected beta-thal carriers and another 16 beta-thal major patients who were being treated in the Philippines were studied to determine the spectrum of beta-globin gene mutations. Gap-PCR was used to detect the Filipino deletion of beta-thal, and direct sequencing was used to detect point or small mutations in the beta-globin gene. All of the 27 suspected beta-thal carriers had one mutation in the beta-globin gene, resulting in an overall prevalence of 0.9%. The spectrum of beta-thal mutations was similar in the carrier and patient groups. Analysis of the pooled identified seven different mutations in the study population. The Filipino deletion was the most common mutation, accounting for 45.8% (27/59) of the alleles, followed by codon 67 (-TG) (16 alleles), and Hb E (11 alleles). These three mutations accounted for 92% of the Filipino beta-thal alleles. Elucidation of the beta-thal mutations in Filipinos is useful for the genetic counseling and prenatal diagnosis of this disease.
Subject(s)
beta-Thalassemia/ethnology , beta-Thalassemia/epidemiology , Alleles , Female , Gene Deletion , Hemoglobin A2/analysis , Homozygote , Humans , Male , Mutation , Philippines/ethnology , Prevalence , Taiwan/epidemiology , beta-Thalassemia/geneticsABSTRACT
Adenomyosis confined to the broad ligament is extremely rare. Herein we present a case of adenomyosis in the broad ligament with unusual gross features. This 41-year-old woman had been on tamoxifen therapy for 3 years due to breast cancer. Ten months after discontinuing tamoxifen, she underwent exploratory laparotomy for a right adnexal mass suspected as ovarian malignancy. At laparotomy, the mass was located in the right broad ligament with a fibrous stalk connecting to the uterus. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. Histopathologic examination revealed adenomyosis with cyst formation and an unusual thick capsule. The possible effects of tamoxifen upon the uterus are discussed in this article, in view of reports of tamoxifen associated with endometrial carcinoma and endometriosis.
