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      • DNA Hypermethylation of Cell Cycle (p15 and p16) and Apoptotic (p14, p53, DAPK and TMS1) Genes in Peripheral Blood of Leukemia Patients

        Bodoor, Khaldon,Haddad, Yazan,Alkhateeb, Asem,Al-Abbadi, Abdullah,Dowairi, Mohammad,Magableh, Ahmad,Bsoul, Nazzal,Ghabkari, Abdulhameed Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1

        Aberrant DNA methylation of tumor suppressor genes has been reported in all major types of leukemia with potential involvement in the inactivation of regulatory cell cycle and apoptosis genes. However, most of the previous reports did not show the extent of concurrent methylation of multiple genes in the four leukemia types. Here, we analyzed six key genes (p14, p15, p16, p53, DAPK and TMS1) for DNA methylation using methylation specific PCR to analyze peripheral blood of 78 leukemia patients (24 CML, 25 CLL, 12 AML, and 17 ALL) and 24 healthy volunteers. In CML, methylation was detected for p15 (11%), p16 (9%), p53 (23%) and DAPK (23%), in CLL, p14 (25%), p15 (19%), p16 (12%), p53 (17%) and DAPK (36%), in AML, p14 (8%), p15 (45%), p53 (9%) and DAPK (17%) and in ALL, p15 (14%), p16 (8%), and p53 (8%). This study highlighted an essential role of DAPK methylation in chronic leukemia in contrast to p15 methylation in the acute cases, whereas TMS1 hypermethylation was absent in all cases. Furthermore, hypermethylation of multiple genes per patient was observed, with obvious selectiveness in the 9p21 chromosomal region genes (p14, p15 and p16). Interestingly, methylation of p15 increased the risk of methylation in p53, and vice versa, by five folds (p=0.03) indicating possible synergistic epigenetic disruption of different phases of the cell cycle or between the cell cycle and apoptosis. The investigation of multiple relationships between methylated genes might shed light on tumor specific inactivation of the cell cycle and apoptotic pathways.

      • Evaluation of BCL-6, CD10, CD138 and MUM-1 Expression in Diffuse Large B-Cell Lymphoma patients: CD138 is a Marker of Poor Prognosis

        Bodoor, Khaldon,Matalka, Ismail,Hayajneh, Rami,Haddad, Yazan,Gharaibeh, Waleed Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.7

        The diffuse large B-cell lymphoma (DLBCL) encompasses two major groups of tumors with uneven survival outcomes - germinal center B-cell (GCB) and non-germinal center B-cell (non-GCB). In the present study, we investigated the expression of GCB markers (BCL-6 and CD10) and non-GCB markers (CD138 and MUM-1) in an effort to evaluate their prognostic value. Paraffin-embedded tumor biopsies of 46 Jordanian DLBCL patients were analyzed, retrospectively, by immunohistochemistry to investigate the expression of BCL-6, CD10, CD138 and MUM-1. In addition, survival curves were calculated with reference to marker expression, age, sex and nodal involvement. Positive expression of BCL-6, CD10, CD138 and MUM-1 was shown in 78%, 61%, 39% and 91% of the cases, respectively, that of BCL-6 being associated with better overall survival (p = 0.02), whereas positive CD138 was linked with poor overall survival (p = 0.01). The expression of CD10 and MUM-1 had no impact on the overall survival. Among the clinical characteristics studied, diagnosis at an early age, nodal involvement and maleness were associated with a higher overall survival for DLBCL patients. Our results underline the importance of BCL-6 as a marker of better prognosis and CD138 as a marker of poor prognosis for DLBCL patients.

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        Urodynamic Detrusor Overactivity in Patients with Overactive Bladder Symptoms

        Mohammed A. Al-Ghazo,Ibrahim Fathi Ghalayini,Rami Al-Azab,Osama Bani Hani,Yousef S. Matani,Yazan Haddad 대한배뇨장애요실금학회 2011 International Neurourology Journal Vol.15 No.1

        Purpose: To evaluate the relationship between urodynamic detrusor overactivity (DO) and overactive bladder (OAB) symptoms in men and women. Methods: We reviewed the records of adult males and females who attended a tertiary referral center for urodynamic evaluation of OAB syndrome symptoms with the presence or absence of DO. DO was calculated for symptoms alone or in combination. Results: The overall incidence of DO was 76.1% and 58.7% in male and female OAB patients, respectively. Of men 63% and 61% of women with urgency (OAB dry) had DO, while 93% of men and 69.8% of women with urgency and urgency urinary incontinence (OAB wet) had DO. Of women, 58% who were OAB wet had stress urinary incontinence symptoms with 26.4% having urodynamic stress incontinence. 6% of men and 6.5% of women with OAB symptoms had urodynamic diagnosis of voiding difficulties with postvoid residual greater than 100 mL. Combination of symptoms is more accurate in predicting DO in OAB patients. The multivariate disease model for males included urge urinary incontinence (UUI) and urgency while for females it included UUI and nocturia. Conclusions: There was a better correlation in results between OAB symptoms and the urodynamic diagnosis of DO in men than in women, more so in OAB wet than in OAB dry. Combination of symptoms of the OAB syndrome seems to have a better correlation with objective parameters from the bladder diary, filling cystometry, and with the occurrence of DO.

      • Heat Shock Protein Association with Clinico-Pathological Characteristics of Gastric Cancer in Jordan : HSP70 is Predictive of Poor Prognosis

        Bodoor, Khaldon,Jalboush, Sara Abu,Matalka, Ismail,Abu-Sheikha, Aya,Waqfi, Rofieda Al,Ebwaini, Hanadi,Abu-Awad, Aymen,Fayyad, Luma,Al-Arjat, Jamal,Haddad, Yazan Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.8

        Gastric cancer (GC) is a major health problem worldwide and is one of the ten most commonly diagnosed cancers in Jordan. GC is usually diagnosed at late aggressive stages in which treatment options are limited. Recently, heat shock proteins (HSPs) were found to be overexpressed in a wide range of malignancies have been considered as promising candidate biomarkers for GC. The aim of this study was to investigate pathogenic roles of a panel of cytosolic HSPs including HSP90, HSP70, HSP60 and HSP27 in GC. Immunohistochemistry was used to assess the level of expression of these proteins in archived tumor samples (N=87) representing various pathological characteristics of GC. HSP90, HSP60 and HSP27 were expressed abundantly in gastric tumors. On the other hand, HSP70 was reduced significantly and also found to be associated with Helicobacter pylori infection in tissues collected from GC patients. Furthermore, HSP27 was found to be associated with the level of differentiation. Our findings indicate a role of HSP70 as a potential prognostic biomarker, patients harboring positive HSP70 expression displaying worse disease free survival than those with negative HSP70 expression. Differential expression of HSPs may play crucial roles in the initiation and progression of GC, and could be exploited as future therapeutic targets.

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