Allelic loss of chromosome region 3p21 is one of the most frequent events in the development of human cancers including lung, breast and bladder cancer. 1-3 A gene called RASSF1 has been discovered recently in this chromosome region. 4 One of the splice variants of this gene, RASSF1A, is inactivated frequently in many cancers including lung, breast and bladder by promoter hypermethylation. 5,6 Therefore both genetic and epigenetic alterations appeared to be involved in the RASSF1A inactivation. Furthermore, re-expression experiment in lung and renal cell carcinoma found that RASSF1A suppressed tumor growth in soft agar assay and in nude mice model. 5,7 These studies suggest that RASSF1A function as a tumor suppressor gene. Based on the presence of the RAS association domain in protein of RASSF1A, it is suggested that it exerts its function through RAS-mediated pathway. 4 More recently, RASSF1A is found to exert its effect by binding with novel RAS effector, Nore1 and MTS1. 8,9 Bladder cancer is the 6th most common cancer in the world. 10 Transitional cell carcinoma comprising the majority of bladder cancer, displays the multiple metachronous or synchronous features. Bladder cancer patients need a long-term follow-up with repeated urine cytology and cystoscopy for monitoring. 11 Conventional urine cytology has been the standard method for cancer detection. The sensitivity is low, however, especially for low grade transitional cell carcinoma (TCC). Therefore, a more sensitive and non-invasive method is required for cancer detection. We have reported previously that promoter hypermethylation of four cancer-related genes can be detected in voided urine of bladder cancer patients and appears to be more sensitive than conventional cytology in cancer detection. 12 In our study, we investigate the frequency of LOH in 3p21 regions and methylation status of RASSF1A in bladder cancer tissues. We also investigate the feasibility of detecting methylation of RASSF1A in voided urine and its potential role as tumor marker for bladder cancer. MATERIAL AND METHODS Tissues samplesForty bladder tumor tissues samples from transurethral resection specimens (8 frozen samples and 32 paraffin-embedded samples) were obtained at the Prince of Wales Hospital. Paraffin-embedded tissues from 6 samples of carcinoma in situ and 6 samples of normal urothelium from individuals without bladder cancer were also included. The clinical pathological data for all the tissue samples are summarized in Table I. Three human bladder cancer cell lines (T24, UMUC3 and J82) were obtained from American Type Culture Collection (Rockville, MD). Urine samplesPaired voided urine samples were collected from 14 patients ( Table I). The urine samples were spun down and the urine sediments were subjected to subsequent analysis. The corresponding urine samples were also subjected to conventional urine cytology examination by an experienced pathologist without knowledge of the methylation results. In Addition, 10 normal voided urine sediments from age-and gender-match c...
A four-day course of high-dose dexamethasone is effective initial therapy for adults with immune thrombocytopenic purpura.
Recent linkage analyses of nondiabetic African-American patients with focal segmental glomerulosclerosis (FSGS) have identified MYH9, encoding nonmuscle myosin heavy chain IIA (NMMHC-IIA), as a gene having a critical role in this disease. Abnormalities of the MYH9 locus also underlie rare autosomal dominant diseases such as May-Hegglin anomaly, and Sebastian, Epstein (EPS), and Fechtner (FTNS) syndromes that are characterized by macrothrombocytopenia and cytoplasmic inclusion bodies in granulocytes. Among these diseases, patients with EPS or FTNS develop progressive nephritis and hearing disability. We analyzed clinical features and pathophysiological findings of nine EPS-FTNS patients with MYH9 mutations at the R702 codon hot spot. Most developed proteinuria and/or hematuria in early infancy and had a rapid progression of renal impairment during adolescence. Renal histopathological findings in one patient showed changes compatible with FSGS. The intensity of immunostaining for NMMHC-IIA in podocytes was decreased in this patient compared with control patients. Thus, MYH9 R702 mutations display a strict genotype-phenotype correlation, and lead to the rapid deterioration of podocyte structure. Our results highlight the critical role of NMMHC-IIA in the development of FSGS.
This study examined the treatment efficacy of PEERS® (Program for the Education and Enrichment of Relational Skills) among Chinese adolescents with autism spectrum disorder (ASD) in Hong Kong. The original PEERS® manual was translated into Chinese, and cultural adjustments were made according to a survey among 209 local adolescents in the general population. 72 high-functioning adolescents with ASD were randomly assigned to a treatment or waitlist control group. The 14-week parent-assisted training significantly improved social skills knowledge and social functioning, and also reduced autistic mannerisms. Treatment outcomes were maintained for 3 months after training and replicated in the control group after delayed treatment. The present study represents one of the few randomized controlled trials on PEERS® conducted outside North America.
Gender‐nonconforming (GN) children are often perceived less positively, which may harm their well‐being. We examined the development of such perceptions and an intervention to modify them. Chinese children’s appraisals were assessed using multiple measures (verbal responses, sharing, and rank order task) after viewing vignettes of gender‐conforming (GC) and GN hypothetical peers. In Study 1, children (N = 210; 4‐, 5‐, 8‐, and 9‐year‐olds) were less positive toward GN than GC peers, especially if they were older or if the peers were boys. In Study 2 (N = 211, 8‐ and 9‐year‐olds), showing children exemplars of GN peers who displayed positive and GC characteristics subsequently reduced bias against gender nonconformity. These findings inform strategies aimed at reducing bias against gender nonconformity.
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