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1.
FEBS Open Bio ; 13(1): 102-117, 2023 01.
Article in English | MEDLINE | ID: mdl-36345604

ABSTRACT

Nasopharyngeal carcinoma (NPC) is a highly metastatic and invasive malignant tumor that originates in the nasopharynx. The DNA-binding protein WD repeat and HMG-box DNA-binding protein 1 (WDHD1) are highly expressed in a variety of tumours, but its expression and mechanism of action in NPC have not been reported to date. To investigate the involvement of WDHD1 in NPC, we first mined databases for the gene expression profile of NPC. Immunohistochemistry (IHC) was performed on 338 cases of NPC and 112 non-NPC samples to verify the results. We report that the expression of WDHD1 is significantly elevated in NPC. ChIP-seq was used to show that integrin alpha V (ITGAV) and WDHD1 exhibit a significant binding peak in the promoter region of the ITGAV gene. The expression levels of ITGAV and WDHD1 exhibit a significant positive correlation, and IHC was performed to show that ITGAV is highly expressed in NPC. Expression of ITGAV increased after overexpression of WDHD1, suggesting that ITGAV may be a potential target gene of WDHD1. Pathway analysis showed that both genes were closely related to the cell cycle, and flow cytometry was used to further confirm that decreased expression of WDHD1 significantly increased the number of apoptotic cells. In conclusion, our results suggest that expression of WDHD1 is increased in NPC and is likely to be associated with the NPC cell cycle; thus, we propose that WDHD1 may have the potential as a target gene for primary screening and treatment of NPC.


Subject(s)
Integrin alphaV , Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Carcinoma/genetics , Cell Line, Tumor , DNA-Binding Proteins , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/metabolism , Nasopharyngeal Neoplasms/pathology
2.
Indian J Hematol Blood Transfus ; 30(4): 253-8, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25435723

ABSTRACT

Much effort has been made to stratify multiple myeloma patients for targeted therapy. However, responses have been varied and improved patient stratifications are needed. Forty-five diagnostic samples from multiple myeloma patients (median age 65 years) were stratified cytogenetically as 15 having non-hyperdiploidy, 20 having hyperdiploidy and 10 having a normal karyotype. Fluorescence in situ hybridization (FISH) assays with FGFR3/IGH, CCND1/IGH, IGH/MAF, RB1 and TP53 probes on bone marrow samples showed that IGH rearrangements were the most common abnormality in the non-hyperdiploid group but these were also found among hyperdiploid patients and patients with normal cytogenetics. Of these, FGFR3/IGH rearrangements were most frequent. Deletion of RB1/monosomy 13 was the most common genetic abnormality across the three groups and was significantly higher among non-hyperdiploid compared to hyperdiploid patients. On the other hand, the study recorded a low incidence of TP53 deletion/monosomy 17. The FGFR3/IGH fusion was frequently seen with RB1 deletion/monosomy 13. FISH with 1p36/1q21 and 6q21/15q22 probes showed that amplification of 15q22 was seen in all of the hyperdiploid patients while amplification of 1q21, Amp(1q21), characterized non-hyperdiploid patients. In contrast, deletions of 1p36 and 6q21 were very rare events. Amp(1q21), FGFR3/IGH fusion, RB1 deletion/monosomy 13, and even TP53 deletion/monosomy 17 were seen in some hyperdiploid patients, suggesting that they have a less than favorable prognosis and require closer monitoring.

3.
Chin Med J (Engl) ; 126(10): 1872-7, 2013.
Article in English | MEDLINE | ID: mdl-23673102

ABSTRACT

BACKGROUND: Much is known about the cytogenetic lesions that characterize multiple myeloma (MM) patients from the USA, Europe, and East Asia. However, little has been published about the disease among Southeast Asians. The aim of this study was to determine the chromosomal abnormalities of MM patients in our Singapore population. METHODS: Forty-five newly-diagnosed, morphologically confirmed patients comprising 18 males and 27 females, aged 46 - 84 years (median 65 years) were investigated by karyotyping and fluorescence in situ hybridization (FISH). FISH employing standard panel probes and 1p36/1q21 and 6q21/15q22 probes was performed on diagnostic bone marrow samples. RESULTS: Thirty-four cases (75.6%) had karyotypic abnormalities. Including FISH, a total detection rate of 91.1% was attained. Numerical and complex structural aberrations were common to both hyperdiploid and non-hyperdiploid patients. Numerical gains of several recurring chromosomes were frequent among hyperdiploid patients while structural rearrangements of several chromosomes including 8q24.1 and 14q32 characterized non-hyperdiploid patients. With FISH, immunoglobulin heavy chain (IGH) gene rearrangements, especially fibroblast growth factor receptor 3 (FGFR3)/IGH and RB1 deletion/monosomy 13 were the most common abnormalities (43.4%). Amplification 1q21 was 10 times more frequent (42.5%) than del(1p36) and del(6q21). CONCLUSIONS: We have successfully reported the comprehensive cytogenetic profiling of a cohort of newly-diagnosed myeloma patients in our population. This study indicates that the genetic and cytogenetic abnormalities, and their frequencies, in our study group are generally similar to other populations.


Subject(s)
Chromosome Aberrations , Multiple Myeloma/genetics , Aged , Aged, 80 and over , Cytogenetics , Female , Humans , Immunoglobulin Heavy Chains , In Situ Hybridization, Fluorescence , Karyotyping , Male , Middle Aged , Monosomy/genetics , Multiple Myeloma/pathology , Receptor, Fibroblast Growth Factor, Type 3/genetics , Retinoblastoma Protein/genetics , Singapore
4.
Guang Pu Xue Yu Guang Pu Fen Xi ; 30(6): 1624-7, 2010 Jun.
Article in Chinese | MEDLINE | ID: mdl-20707163

ABSTRACT

Satellite sensor technology endorsed better discrimination of various landscape objects. Image segmentation approaches to extracting conceptual objects and patterns hence have been explored and a wide variety of such algorithms abound. To this end, in order to effectively utilize edge and topological information in high resolution remote sensing imagery, an object-oriented algorithm combining edge detection and region merging is proposed. Susan edge filter is firstly applied to the panchromatic band of Quickbird imagery with spatial resolution of 0.61 m to obtain the edge map. Thanks to the resulting edge map, a two-phrase region-based segmentation method operates on the fusion image from panchromatic and multispectral Quickbird images to get the final partition result. In the first phase, a quad tree grid consisting of squares with sides parallel to the image left and top borders agglomerates the square subsets recursively where the uniform measure is satisfied to derive image object primitives. Before the merger of the second phrase, the contextual and spatial information, (e. g., neighbor relationship, boundary coding) of the resulting squares are retrieved efficiently by means of the quad tree structure. Then a region merging operation is performed with those primitives, during which the criterion for region merging integrates edge map and region-based features. This approach has been tested on the QuickBird images of some site in Sanxia area and the result is compared with those of ENVI Zoom Definiens. In addition, quantitative evaluation of the quality of segmentation results is also presented. Experiment results demonstrate stable convergence and efficiency.

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