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Biomedical subjects

Han Kwang Yang

Publications and source records attributed to Han Kwang Yang.

5 recordsLinked to original sources

Immune pathway activation in gastric cancers with LINE-1 retrotransposon overexpression and homologous recombination deficiency.

There are only a few whole genome sequencing studies of human gastric cancer (GC) conducted so far. We performed comprehensive whole genome, bulk RNA, and methylation sequencing analyses of 100 samples of GC and adjacent normal tissue. In a smaller non-EBV/non-MSI subset (n = 23), we also performed proteomic profiling by mass spectrometry. We validated the proteomic findings in an independent dataset. Using this unprecedented dataset of human GC samples, we examined the extent of chromothripsis, homologous recombination deficiency, and retrotransposition, and correlated these events with patient outcomes. We found that chromothripsis occurred in 22% of GCs and correlated with poor prognosis. Multichromosomal chromothripsis was associated with a particularly high risk of death. Based on copy number (CN) signature analysis, we identified a distinct non-CN9 subgroup with significantly worse outcomes. Homologous recombination deficiency was present in 4% of GCs and was associated with overexpression of immune signaling pathways. Somatic retrotransposition events were most strongly associated with global hypomethylation. We also identified BYSL as a putative oncogenic driver within the 6p21 locus whose amplification is associated with poor prognosis. Collectively, our findings provide novel insights into the dysregulation of DNA stability and repair and their clinical relevance in human GCs.

Journal Article↗

Effect of adjusted positioning on gastric distention and fluid distribution during CT gastrography.

OBJECTIVE: We hypothesized that performing CT gastrography with the patient in the left posterior oblique (LPO) position would provide better distention and less residual fluid for the lower part of the stomach than CT gastrography with the patient in the standard supine position. CONCLUSION: The LPO position for CT guaranteed the distensibility of and minimal residual fluid in the lower part of the stomach, thus resulting in excellent 3D CT gastrographic images.

Adult↗

Loss of caspase-1 gene expression in human gastric carcinomas and cell lines.

The caspases are a family of aspartic acid-specific proteases that fulfill varied and often critical roles in mammalian apoptosis or in the proteolytic activation of cytokines. Caspase-1 (interleukin-1beta-converting enzyme) is a member of the cysteine protease family, which cleaves target proteins following aspartic acid residues. We investigated caspase-1 expression in stomach cancer, tissues and cell lines. Of 301 consecutive gastric carcinomas, 58 cases (19.3%) showed the expressional loss of caspase-1. Loss of caspase-1 expression was significantly associated with pTNM stage (p=0.03), lymph node metastasis (p=0.01) and patient survival (p<0.01). Caspase-1 expression was also significantly correlated in an inverse manner with p53 expression (p<0.01). Among the 11 gastric cancer cell lines examined, three cell lines showed loss of expression at the protein and mRNA levels. On treatment with 5-aza-2'-deoxycytidine (5-aza-C), and/or trichostatin A (TSA), all three cell lines re-expressed caspase-1 mRNA. The above findings suggest that epigenetic events such as DNA methylation and histone deacetylation play important roles in the regulation of caspase-1, and that loss of caspase-1 expression is associated with poor survival in gastric carcinoma.

Antimetabolites, Antineoplastic↗

Computed tomography gastrography with volume-rendering technique: correlation with double-contrast barium study and conventional gastroscopy.

The volume-rendering technique uses computed tomography data to produce simulated images of conventional barium and endoscopic studies of the stomach. Various gastric lesions are detected on volume-rendered images, and submucosal tumors are easily differentiated from mucosal lesions by means of the overlying bridging fold. Lesions that are only manifested by a change of mucosal color (early gastric cancer type 2b) or a loss of mucosal detail (gastritis) are difficult to detect from volume-rendered images, however. In cases of gastric neoplasm and varix, both the extraluminal pathologies of the lesion and the relation between the intraluminal and extraluminal components can be evaluated simultaneously.

Adenomatous Polyps↗

Expression of family A melanoma antigen in human gastric carcinoma.

BACKGROUND: Since the members of the MAGE (melanoma antigen) gene family have been reported to be expressed in tumor cells but not in normal tissues, they have been considered as targets for tumor-specific immunotherapy. MATERIALS AND METHODS: The expression pattern of MAGE-A genes and their expression mechanisms were investigated in 10 gastric cancer cell lines and 1,097 gastric carcinoma specimens by RT-PCR, IHC, Western blot and MSP. RESULTS: MAGE-A1, -A2 and -A3 gene transcripts were detected in 1, 3 and 4 of 10 gastric cancer cell lines, respectively. In those cases in which the mRNA expression of MAGE-A2 or -A3 was detected, the promoters of the corresponding genes were hypomethylated. MAGE-A protein expression was detected in 30% (3/10) of the cell lines and 15.8% (173 out of 1,097) of the carcinoma specimens. Promoter hypomethylation of the MAGE-A2 or -A3 genes correlated with their expression in primary gastric cancer tissue and gastric cancer cell lines. MAGE-A protein expression was associated with tumor invasiveness (p=0.002), lymph node metastasis (p<0.001), advanced pathologic stage (p<0.001) and a worse prognosis (p<0.005). CONCLUSION: MAGE-A protein expression occurred due to promoter hypomethylation in a minor subset of gastric cancers, and MAGE-A expression increased during the progression of the gastric cancer.

Antigens, Neoplasm↗