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1.
Hum Immunol ; 84(3): 186-195, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36725456

ABSTRACT

Several studies have reported an association between certain human leukocyte antigen (HLA) alleles and carbamazepine (CBZ)-induced hypersensitivity reactions in patients with epilepsy. Here, the relationship between the clinical spectrum and the HLA allele profiles in patients with CBZ-induced hypersensitivity reactions was investigated using next-generation sequence (NGS) data obtained from 65 Vietnamese patients with epilepsy, including 33 with CBZ-tolerance and 32 patients with CBZ-hypersensitivity, in which only 8 with severe cutaneous adverse drug reactions and 24 were mild-hypersensitive patients. Three loci of HLA class I (HLA-A, -B, and -C) and two loci of HLA class II (HLA-DQA1 and -DRB1) were included in our analysis. We observed a higher prevalence of three alleles, HLA-B*46:01:01, HLA-DQA1*03:02:01, and HLA-DRB1*09:01:02, in the CBZ hypersensitivity group compared to that in the CBZ tolerant group. Notably, all hypersensitive patients with HLA-DQA1*03:02:01 also harbored HLA-DRB1*09:01:02. We also used molecular modeling to gain mechanistic insight into the interactions of HLA-B*46:01 and HLA-DRB1*09:01 with CBZ. Our findings proposed the direct interaction of CBZ with peptide-binding pockets of these HLA proteins. The sensitivity and specificity of HLA-B*46:01:01 in considering with the appearance of HLA-DRB1*09:01:02 were 46.88% and 84.85%, respectively. Our data suggest that the presence of HLA-B*46:01:01/HLA-DRB1*09:01:02 is a potential marker of CBZ-induced hypersensitivity reactions in Vietnamese patients.


Subject(s)
Carbamazepine , Drug Hypersensitivity , Epilepsy , HLA-B Antigens , HLA-DRB1 Chains , Humans , Alleles , Anticonvulsants/adverse effects , Carbamazepine/adverse effects , Drug Hypersensitivity/genetics , Epilepsy/drug therapy , High-Throughput Nucleotide Sequencing , Histocompatibility Testing , HLA-B Antigens/genetics , HLA-DRB1 Chains/genetics , Southeast Asian People
2.
Asian Pac J Cancer Prev ; 23(6): 1893-1900, 2022 Jun 01.
Article in English | MEDLINE | ID: mdl-35763629

ABSTRACT

BACKGROUND: Considering the poor prognosis of non-small cell lung cancer (NSCLC), the objective of this study was to examine the potential of plasma-derived vesicles as a source of lung cancer-specific proteins. Extracellular vesicle (EV) cargos are specific to the source cells, hence they have the potential of being a source of cancer-specific proteins.  Methods: The proteins differently expressed in cancer were determined and derived from EVs isolated from the plasma of NSCLC patients at the National Lung Hospital. To this end, purification was done using gel filtration chromatography and ultracentrifugation. In addition, nano liquid chromatography mass spectrometry (LC-MS/MS) was used for analyzing. RESULTS: Fifty-seven EV-derived proteins related to NSCLC were highlighted in this research. Some of them have not been addressed before, such as EEF1A1 (elongation factor 1-α1), KPNB1 (Importin subunit beta 1), SRC (proto-oncogene tyrosine-protein kinase) and ACTC1 (actin, alpha cardiac muscle 1). This list was further confirmed through a comparison with ExoCarta and Vesiclepedia. CONCLUSION: This study is the first work to show the involvement of several novel proteins of small EV (EEF1A1, KPNB1, SRC, and ACTC1) in the progression of NSCLC. The results suggested that they could serve as novel biomarkers for non-small cell lung cancer in the future.
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Subject(s)
Carcinoma, Non-Small-Cell Lung , Extracellular Vesicles , Lung Neoplasms , Asian People , Biomarkers , Chromatography, Liquid , Humans , Proteomics , Tandem Mass Spectrometry
3.
Oncol Lett ; 13(4): 2097-2104, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28454367

ABSTRACT

Matrix metalloproteinases (MMPs), a family of endopeptidases also known as gelatinases, have been reported to affect the acquisition of the cell proliferative, cell invasive and metastatic phenotype of several types of cancer. In particular, the gelatinases MMP-2 and -9 have been revealed to facilitate tumor growth and invasion in patients with colorectal cancer (CRC). However, it is not known whether the gelatinase activity of MMP-2 and -9 is also elevated in Vietnamese patients with CRC. The activity of MMP-2 and -9 in the tissue samples of 103 patients with CRC was evaluated by gelatin zymography and quantified using ImageJ. The association between the level of activity of MMP-2 and -9 and various clinicopathological factors was analyzed, and Chisio BioPAX Editor software was used to visualize the biological pathways regulating the activity of the MMPs. The present study noticed significantly increased activity of active MMP-2 and MMP-9 in tumor tissues (P<0.01), and significantly decreased levels of pro-form MMP-2 and MMP-9 in tumor tissues (P<0.01), compared with that in adjacent tissues in patients with CRC. A correlation between the normalized different activity of MMP-2 and -9 and various clinicopathological features was observed. Furthermore, bioinformatics analysis indicated that the alteration in the activity of MMP-2 and MMP-9 may have been controlled by biological pathways involving the tissue inhibitors of metalloprotease-2 and -1. These findings indicate that the activity of the gelatinases MMP-2 and -9 affects the tumor progression and metastasis of patients with CRC, providing a potential novel approach for determining the prognosis of CRC.

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