• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.5
• /
• pp.2309-2312
• /
• 2014

Esophageal squamous cell carcinoma (ESCC) is the most common histologic subtype of esophageal cancer and is characterized by a poor prognosis. Determining gene changes in ESCCs should improve understanding of putative risk factors and provide potential targets for therapy. We sequenced about 55 million pair-end reads from a pair of adjacent normal and ESCC samples to identify the gene expression level and gene fusion. Sanger sequencing was used to verify the result. About 17 thousand genes were expressed in the tissues, of which approximately 2400 demonstrated significant differences between tumor and adjacent non tumor tissue. GO and KEGG pathway analysis revealed that many of these genes were associated with cellular adherence and movement, simulation responses and immune responses. Notably we identified and validated one fusion gene, HLA-E and HLA-B, located 1 MB apart. We also identified thousands of remarkably expressed transcripts. In conclusion, a novel fusion gene HLA-E and HLA-B was identified in ESCC via whole transcriptome sequencing, which would be a biomarker for ESCC diagnosis and target for therapy, shedding new light for better understanding of ESCC tumorigenesis.

• Journal of Genetic Medicine
• /
• v.14 no.1
• /
• pp.18-22
• /
• 2017

Pseudohypoparathyroidism type 1b (PHP 1b) is the result of end organ resistance to parathyroid hormone (PTH) in the absence of any features of Albright's hereditary osteodystrophy. There are two subtypes of PHP 1b with different genetic mechanisms. One subtype is related to a maternally derived 3kb microdeletion involving STX 16 gene, and is inherited in an autosomal dominant mode. Familial autosomal dominant inheritance of PHP 1b is relatively rare. The other subtype is associated with more extensive loss of imprinting at the GNAS locus that affects at least one additional differential methylated (hypermethylation at neuroendocrine secretory protein and hypomethylation at antisense transcript and or extra-large stimulatory G protein region) without microdeletion of the STX 16 or AS gene. It can be sporadic due to an imprinting defect in the GNAS gene. In our case, an 8-year-old girl was referred for suspected PHP with no feature of Albright hereditary osteodystrophy. Blood test results revealed hypocalcemia and hyperphosphatemia. Elevated PTH was also checked. There was no family history of endocrine or developmental problem. Her intelligence was normal, but she had inferior sociability at that time. Based on above, we diagnosed a rare case of paternal uniparental disomy of the long arm of chromosome 20 as the cause of PHP 1b by microsatellite marker test of chromosome 20.

• Journal of the Korea Convergence Society
• /
• v.10 no.8
• /
• pp.59-65
• /
• 2019

There are various subtypes of cells in cancer tissues, but it is hard to confirm their composition experimentally. Here, we estimated the cell composition of each sample from gene expression data by using statistical machine learning approaches, two different regression models and investigated whether the cell composition was different between cancer and normal tissue. As a result, we found that CD8 T cell and Neutrophil were increased in oral cancer tissues compared to normal tissues. In addition, we applied t-SNE, which is one of the unsupervised learning, to verify whether normal tissue and oral cancer tissue can be clustered by the derived cell composition. Moreover, we showed that it is possible to predict oral cancer and normal tissue by several supervised classification algorithms. The study would help to improve the understanding of the immune cell infiltration at oral cancer.

• Biomolecules & Therapeutics
• /
• v.26 no.3
• /
• pp.290-297
• /
• 2018

We aimed to understand the molecular changes in host cells that accompany infection by the seasonal influenza A H1N1 virus because the initial response rapidly changes owing to the fact that the virus has a robust initial propagation phase. Human epithelial alveolar A549 cells were infected and total RNA was extracted at 30 min, 1 h, 2 h, 4 h, 8 h, 24 h, and 48 h post infection (h.p.i.). The differentially expressed host genes were clustered into two distinct sets of genes as the infection progressed over time. The patterns of expression were significantly different at the early stages of infection. One of the responses showed roles similar to those associated with the enrichment gene sets to known 'gp120 pathway in HIV.' This gene set contains genes known to play roles in preventing the progress of apoptosis, which infected cells undergo as a response to viral infection. The other gene set showed enrichment of 'Drug Metabolism Enzymes (DMEs).' The identification of two distinct gene sets indicates that the virus regulates the cell's mechanisms to create a favorable environment for its stable replication and protection of gene metabolites within 8 h.

• Journal of Chest Surgery
• /
• v.36 no.11
• /
• pp.852-857
• /
• 2003

Background: Conventional treatment for mesothelioma is largely ineffective. We evaluated the novel approach of adenoviral gene transfection of PTEN gene in mesothelioma cancer cell lines, inflammatory and epithelial subtype, which are sensitive to adenoviral p53. Material and Method: Binary adenoviral PTEN and LacZ (Ad/GT-LacZ and Ad/GV16) vectors were used for transduction of the mesothelioma cell lines, REN (p53 sensitive). Protein levels were determined by Western blotting assay. Apoptosis was assessed by fluorescence-activated cell sorter analysis of subdiploid populations. Cell viability was determined with the XTT assay. Statistical analysis was performed with analysis of variance and the Student t test. Result: 72 hours after the treatment of adenoviral PTEN gene, cell killing were 32.9% for REN compared to control cell (2.5%) at MOI of 20. Also we observed the over-expression of proapoptotic protein, bax and decreased expression of bcl-2 protein in REN cells. But the expression of BCL-xl, Bak, Bad proteins were not altered. Conclusion: Adenovirus Pten-mediated overexpression of the Bax gene induces apoptosis and decreased cellular viability in p53-sensitive mesothelioma cells. These data suggest that the transfection of PTEN gene may represent a alternative gene therapy strategy to treat mesothelioma.

• Journal of Embryo Transfer
• /
• v.33 no.4
• /
• pp.195-203
• /
• 2018

Interferon-tau (IFNT) is known as a major conceptus protein that signals the process of maternal recognition of pregnancy in ruminants. Also, multiple interferon genes exist in cattle, However, molecular mechanisms of these bovine IFNT (bIFNT) genes whose expressions are limited have not been characterized. We and others have observed that expression levels of bovine subtype IFNT genes in the tissues of ruminants; thus, bIFNT1 and other new type I (bIFNTc1/c2/c3) gene co-exist during the early stages of conceptus development and non-trophoblast cells. Its genes transcription could be regulated through CDX2 and ETS2 and JUN and/or cAMP-response element binding protein (CREB)-binding protein (CREBBP) expression, a transcription factor implicated in the control of cell differentiation in the trophectoderm. Bovine ear-derived fibroblast cells, were co-transfected with luciferase reporter constructs carrying upstream (positions -1000 to +51) regions of bIFNT1 and other new type I gene and various transcription factor expression plasmids. Compared to each - 1kb-bIFNT1/c1/c2/c3-Luc increased when this constructs were co-transfected with CDX2, ETS2, JUN and/or CREBBP. Also, Its genes was had very effect on activity by CDX2, either alone or with the other transcription factors, markedly increased luciferase activity. However, the degree of transcriptional activation of the bIFNTc1 gene was not similar to that bIFNT1/c2/c3 gene by expression plasmid. Furthermore, Sequence analyses also revealed that the expression levels of bIFNT1/c2/c3 gene mRNAs expression were highest on day 17, 20 and 22 trophoblast and, Madin-Darby bovine kidney (MDBK), Bovine ear-derived fibroblast (EF), and endometrium (Endo) non-trophoblast cells. But, bIFNTc1 mRNA had not same expression level, bIFNTc1 lowest levels than those of IFNT1/c2/c3 gene in both trophoblast and non-trophoblast cells. These results demonstrate that bovine subtype bIFNT genes display differential, in the trophoblast and non-trophoblast cells.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.15
• /
• pp.6211-6217
• /
• 2014

Previous genome-wide association studies (GWAS) have implicated several single nucleotide polymorphisms (SNPs) in the AT-rich interactive domain 5B (ARID5B) gene with childhood acute lymphoblastic leukemia (ALL). However, replicated studies reported some inconsistent results in different populations. Using meta-analysis, we here aimed to clarify the nature of the genetic risks contributed by the two polymorphisms (rs10994982, rs7089424) for developing childhood ALL. Through searches of PubMed, EMBASE, and manually searching relevant references, a total of 14 articles with 16 independent studies were included. Odds ratios (ORs) with 95% confidence intervals (95%CI) were calculated to assess the associations. Both SNPs rs10994982 and rs7089424 showed significant associations with childhood ALL risk in all genetic models after Bonferroni correction. Furthermore, subtype analyses of B-lineage ALL provided strong evidence that SNP rs10994982 is highly associated with the risk of developing B-hyperdiploid ALL. These results indicate that SNPs rs10994982 and rs7089424 are indeed significantly associated with increased risk of childhood ALL.

• Journal of Veterinary Science
• /
• v.23 no.2
• /
• pp.24.1-24.10
• /
• 2022

Background: Small interfering RNA technology has been considered a prospective alternative antiviral treatment using gene silencing against influenza viruses with high mutations rates. On the other hand, there are no reports on its effectiveness against the highly pathogenic avian influenza H5N1 virus isolated from Indonesia. Objectives: The main objective of this study was to improve the siRNA design based on the nucleoprotein gene (siRNA-NP) for the Indonesian H5N1 virus. Methods: The effectiveness of these siRNA-NPs (NP672, NP1433, and NP1469) was analyzed in vitro in Marbin-Darby canine kidney cells. Results: The siRNA-NP672 caused the largest decrease in viral production and gene expression at 24, 48, and 72 h post-infection compared to the other siRNA-NPs. Moreover, three serial passages of the H5N1 virus in the presence of siRNA-NP672 did not induce any mutations within the nucleoprotein gene. Conclusions: These findings suggest that siRNA-NP672 can provide better protection against the Indonesian strain of the H5N1 virus.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.2
• /
• pp.459-462
• /
• 2012

Expression of estrogen-receptor (ER), progesterone-receptor (PR) and HER-2 has recently been linked with various breast cancer subtypes identified by gene microarray. This study aimed to document breast cancer subtypes based on ER, PR and HER-2 status in Thai women, where expression of these subtypes may not be similar to those evident in Western women. During 2009 to 2010, histological findings from 324 invasive ductal carcinomas (IDC) at Siriraj Hospital were studied. Various subtypes of IDC were identified according to expression of ER, PR and HER-2: luminal-A (ER+;PR+/-;HER-2-), luminal-B (ER+;PR+/-;HER-2 +), HER-2 (ER-;PR- ;HER-2+) and basal-like (ER-;PR-;HER-2-). As well, associations of tumor size, tumor grade, nodal status, angiolymphatic invasion (ALI), multicentricity and multifocality with different breast cancer subtypes were studied. Of 324 IDCs, 143 (44.1%), 147 (45.4%), 15 (4.6%) and 12 (3.7%) were T1, T2, T3 and T4, respectively. Most tumors were grade 2 (54.9%) and had no nodal involvement (53.4%). According to ER, PR and HER-2 status, 192 (59.3%), 40 (12.3%), 43 (13.3%) and 49 (15.1%) tumors were luminal-A, luminal-B, HER-2 and basal-like subtypes. HER-2 subtype presented with large tumor (p=0.04, ANOVA). Luminal-A IDC was associated with single foci (p<0.01, ${\chi}^2$). HER-2 and basal-like subtypes were likely to have high tumor grade (p<0.01, ${\chi}^2$). In addition, HER-2 subtype had higher number of nodal involvement (p=0.048, ${\chi}^2$). In conclusion, the luminal-A subtype accounted for the majority of IDCs in Thai women. Percentages of HER-2 and basal-like IDCs were high, compared with a recent study from the USA. The HER-2 subtype was related with high nodal invasion. The findings may highlight biological differences between IDCs occurring in Asian and Western women.

• The Korean Journal of Pain
• /
• v.22 no.1
• /
• pp.21-27
• /
• 2009

Background: The neuropathic pain arising from nerve injury is difficult to treat and the therapeutic effects of opioid drugs remain debatable. Agonists acting at the ${\alpha}_2$ adrenergic and opioid receptors have analgesic properties and they act synergistically when co-administered in the spinal cord. The lack of subtype-selective pharmacological agents has previously impeded the synergistic effects that are mediated by the adrenergic receptor subtypes. Methods: We created neuropathic pain model by ligating the L5 spinal nerve in Sprague-Dawley rats (n = 18). We divided the rats into three groups (n = 6 for each group), and we administered intraperitoneal morphine (1 mg/kg, 3 mg/kg, 5 mg/kg) and then we measured the mechanical allodynia with using von-Frey filaments for 8 hours. We then injected morphine (5 mg/kg) intraperitoneally, twice a day for 2 weeks. We measured the tactile and cold allodynia in the morphine group (n = 9) and the saline group (n = 9). After 2 weeks, we decapitated the rats and harvested the spinal cords at the level of lumbar enlargement. We compared the ${\alpha}_2$ subtype mRNA expression with that of control group (n = 6) by performing real time polymerase chain reaction (RTPCR). Results: Intraperitoneal morphine reduced the neuropathic pain behavior in the dose-dependent manner. Chronic morphine administration showed an antiallodynic effect on the neuropathic pain rat model. The rats did not display tolerance or hyperalgesia. The expression of the mRNAs of the ${\alpha}_{2A}$, ${\alpha}_{2B}$, ${\alpha}_{2C}$ subtypes decreased, and morphine attenuated this effect. But we could not get statistically proven results. Conclusions: Systemic administration of morphine can attenuate allodynia during both the short-term and long-term time course. Morphine has an influence on the expression of ${\alpha}_2$ receptor subtype mRNA. Yet we need more research to determine the precise effect of morphine on the ${\alpha}_2$ subtype gene expression.