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RNA editing in <i>RHOQ</i> promotes invasion potential in colorectal cancer
Han, Sae-Won,Kim, Hwang-Phill,Shin, Jong-Yeon,Jeong, Eun-Goo,Lee, Won-Chul,Kim, Keon Young,Park, Sang Youn,Lee, Dae-Won,Won, Jae-Kyung,Jeong, Seung-Yong,Park, Kyu Joo,Park, Jae-Gahb,Kang, Gyeong Hoon The Rockefeller University Press 2014 The Journal of experimental medicine Vol.211 No.4
<P>RNA editing can increase RNA sequence variation without altering the DNA sequence. By comparing whole-genome and transcriptome sequence data of a rectal cancer, we found novel tumor-associated increase of RNA editing in <I>ras homologue family member Q</I> (<I>RHOQ</I>) transcripts. The adenosine-to-inosine (A-to-I) editing results in substitution of asparagine with serine at residue 136. We observed a higher level of the <I>RHOQ</I> RNA editing in tumor compared with normal tissue in colorectal cancer (CRC). The degree of RNA editing was associated with RhoQ protein activity in CRC cancer cell lines. RhoQ N136S amino acid substitution increased RhoQ activity, actin cytoskeletal reorganization, and invasion potential. <I>KRAS</I> mutation further increased the invasion potential of RhoQ N136S in vitro. Among CRC patients, recurrence was more frequently observed in patients with tumors having edited <I>RHOQ</I> transcripts and mutations in the <I>KRAS</I> gene. In summary, we show that RNA editing is another mechanism of sequence alteration that contributes to CRC progression.</P>
Methylation and microsatellite status and recurrence following adjuvant FOLFOX in colorectal cancer
Han, Sae‐,Won,Lee, Hyun‐,Jung,Bae, Jeong Mo,Cho, Nam‐,Yun,Lee, Kyung‐,Hun,Kim, Tae‐,Yong,Oh, Do‐,Youn,Im, Seock‐,Ah,Bang, Yung‐,Jue,Jeong, Seung‐ Wiley Subscription Services, Inc., A Wiley Company 2013 International journal of cancer: Journal internati Vol.132 No.9
<P><B>Abstract</B></P><P>The prognostic impact of CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) on the treatment outcome of colon cancer patients receiving adjuvant 5‐fluorouracil/leucovorin/oxaliplatin (FOLFOX) is unclear. We investigated CIMP and MSI status in colorectal cancer patients treated with adjuvant FOLFOX. Stages II and III sporadic colorectal cancer patients who underwent curative resection followed by adjuvant FOLFOX were included. Eight CpG island loci (CACNA1G, CRABP1, IGF2, MLH1, NEUROG1, CDKN2A (p16), RUNX3 and SOCS1) and five microsatellite markers were examined. Disease‐free survival (DFS) was analyzed according to CIMP and MSI status. A total of 322 patients were included: male/female 192/130, median age 61 years (range 30–78), proximal/distal location 118/204 and Stages II/III 43/279. CIMP status was high in 25 patients (7.8%) and 21 patients (6.5%) had MSI‐high tumor. CIMP/MSI status was not significantly associated with DFS: 3‐year DFS 100% in CIMP(−)/MSI(+), 84% in CIMP(−)/MSI(−), 82% in CIMP(+)/MSI(−) and 75% in CIMP(+)/MSI(+) (<I>p</I> = 0.33). Results of exploratory analysis showed that concurrent methylation at NEUROG1 and CDKN2A (p16) was associated with shorter DFS: 3‐year DFS 69% in NEUROG1(+)/CDKN2A (p16)(+) versus 87% in NEUROG1(−)/CDKN2A (p16)(−) (<I>p</I> = 0.006). In conclusion, concurrent methylation of NEUROG1 and CDKN2A (p16) is associated with recurrence following adjuvant FOLFOX in Stages II/III colorectal cancer.</P>
Over Expression of Aminopeptidase N has Negative Effect on Boar Fertility
Won-Ki Pang,Kyu-Ho Kang,Ki-Uk Kim,Ki-Jin Kwon,Sae-Han Kang,Amena Khatun,Do-Yeal Ryu,Md Saidur Rahman,Myung-Geol Pang 한국동물생명공학회(구 한국동물번식학회) 2017 발생공학 국제심포지엄 및 학술대회 Vol.2017 No.10
Artificial insemination is a commonly used technology in the porcine industry that directly linked to the genetic upgradation of future progeny and profitable farm management. Therefore, accurate prediction of boar fertility is a matter of paramount importance. Although prediction of semen/sperm fertility using conventional analysis provides a preliminary assumption of male fertility, its practical value is limited. Protein content in the cell provides an important and fascinating insight to the dynamics of cell function. Therefore, the study of protein function in spermatozoa and their corresponding relationship with male fertility might be an excellent alternative tool for more accurate prediction of male fertility. Recently we demonstrated that aminopeptidase N (APN) activity is negatively correlated with motility and fertility of mice spermatozoa. Here, we investigated whether APN is also correlated with the fertility of boar. Spermatozoa were collected from high and low fertility boar based on their field fertility data (average litter size 13.2±0.06 and 11.1±0.14, respectively). Simultaneously, APN levels were examined by Western blotting using the corresponding antibody. In addition, spermatozoa from both fertility groups were examined by conventional semen analysis such as computer assisted sperm analysis (CASA) and chlorotetracycline (CTC) staining. Our data showed a significant higher APN expression in low fertility boar spermatozoa compare to the fertile counterpart (p<0.05). Interestingly, no significant difference was noticed in motility, motion kinematics, and capacitation status between both groups. Based on this findings, it is tempting to speculate that APN activity might directly correlate with boar fertility. Therefore, APN activity in spermatozoa is more accurate and sensitive biomarker for the detection of boar fertility then conventional semen analysis. However, further studies and needed to confirm our initial findings
Han, Sae-Won,Jeon, Yoon Kyung,Lee, Kyung-Hun,Keam, Bhumsuk,Hwang, Pil Gyu,Oh, Do-Youn,Lee, Se-Hoon,Kim, Dong-Wan,Im, Seock-Ah,Chung, Doo Hyun,Heo, Dae Seog,Bang, Yung-Jue,Kim, Tae-You Lippincott Williams Wilkins, Inc. 2007 PHARMACOGENETICS AND GENOMICS Vol.17 No.5
OBJECTIVE: Limited availability of tumoral tissue in non-small-cell lung cancer and presence of epidermal growth factor receptor mutation-independent responses call for investigation of other molecular predictive marker of gefitinib responsiveness. Therefore, CA repeat polymorphism in intron 1 was analyzed for its association with gefitinib responsiveness together with epidermal growth factor receptor mutation in Korean patients. PATIENTS AND METHODS: For 86 advanced non-small-cell lung cancer patients treated with gefitinib, epidermal growth factor receptor mutation was analyzed by direct sequencing (exons 18–21) from tumor tissue and CA repeat polymorphism was assessed by fragment length analysis from tumor and/or normal tissue. RESULTS: CA repeat status was identical in 33 patients with matched tumor and normal tissue. CA repeat was low (sum of both alleles ≤37) in 40 (46.5%) and high (sum ≥38) in 46 (53.5%) patients. Although epidermal growth factor receptor mutation was more frequent in high CA repeat patients [17.5% (7/40) in low vs. 28.3% (13/46) in high, P=0.18], response rate was higher in low CA repeat patients [25.0% (10/40) in low vs. 13.0% (6/46) in high, P=0.16]. In multivariate analysis, low CA repeat was associated with better objective response (odds ratio 7.1, 95% confidence interval 1.2–40.8; P=0.029) and time-to-progression (hazard ratio 0.54, 95% confidence interval 0.34–0.88; P=0.014), independent of the epidermal growth factor receptor mutational status. CA repeat status was not associated with epidermal growth factor receptor expression. CONCLUSION: Low number of CA repeats in intron 1 of epidermal growth factor receptor is associated with gefitinib responsiveness in non-small-cell lung cancer patients independent of epidermal growth factor receptor mutation.
Establishment of Hepatoma Treatment Model Using Hepatoma Cell Spheroids
( Han Seul Park ),( Jae Young Jang ),( Seoung Won Jeong ),( Sae Hwan Lee ),( Sang Gyune Kim ),( Sang-woo Cha ),( Young Seok Kim ),( Young Deok Cho ),( Hong Soo Kim ),( Boo Sung Kim ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1
Aims: Three dimensional (3D) spheroid cells are more closely mimic natural tissues and organs than cells grown in 2D. ``Biocompatible spheroidal hepatoma cell`` is thought to be closest model of real patient``s HCC. We have made spheroidal hepatoma cells using the proven technology and already confirmed apoptotic effect of ginsenoside Rh2 and Rg5 on 2D cells (Huh7 and Huh7.5.1). In this study, we investigate apoptotic effects of ginsenoside Rh2 and Rg5 using 3D hepatoma cell spheroids. Methods: Huh7 and Huh7.5.1 cells were maintained in culture dishes in RPMI supplemented with 10% inactivated fetal bovine serum (FBS) and DMEM supplemented with 10 % dialyzed FBS, respectively. When they reached about 80 % confluence, cells were harvested from 2-D petri-dish cultures by treatment with trypsin. These cells cultured in 1.5 % soft agarose gels for 10-14 days. After 10-14 days, 3-D hepatic structure was formed and treated with ginsenoside Rh2 (100, 200uM) and Rg5 (10, 50, 100uM) for 72h. Comparison between 2-D and 3-D models was done with microscopic and protein analysis. Results: The behaviors of 2D and 3D cells (Huh7 and Huh7.5.1, respectively) have been shown different morphologic change. 3-D culture of Huh7 and Huh7.5.1 cells had a longer survival time rather than 2-D cell model. The response to ginsenoside Rh2 and Rg5 on 3D culture systems showed a lower cell death rate compared with 2D culture systems. The expression of cleaved PARP protein was increased in both 2D and 3D cells with exposure to ginsenoside Rh2 and Rg5. Conclusions: Hepatoma cell sheroids had a longer survival time and a similar apoptotic effect compared to 2-D cell model in drug screening. It is expected to have an important role on the drug screening and treatment prediction in HCC.
( Han Seul Park ),( Jae Young Jang ),( Soung Won Jeong ),( Jeong-ju Yoo ),( Sae Hwan Lee ),( Sang Gyune Kim ),( Sang-woo Cha ),( Young Seok Kim ),( Young Deok Cho ),( Hong Soo Kim ),( So Young Jin ),( 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
Aims: Animal & cell models of hepatoma give a crucial information, not only pathogenesis of liver cancer but also therapeutic effects of various agents. In this study, we investigate therapeutic effects of ginsenoside Rh2 and Rg5 using animal & cell models of hepatoma comparing with sorafenib. Methods: Huh7 & huh7.5.1 cells were harvested from 2-D petri-dish and cultured in 1.5 % soft agarose gels for 10-14 days. After 10-14 days, 3-D hepatic structure was formed and treated with ginsenoside Rh2 (100, 200uM) and Rg5 (10, 50, 100uM) for 72h. Hep3b cells (2×10<sup>5</sup>) in matrigel were suspended in 100 μl of phosphate-buffered saline (PBS) and then injected into the flanks of BALB/C nude mouse at 6 weeks. Sorafenib (10mg/kg), ginsenoside Rh2 (100 uM) and Rg5 (100 uM) was injected to intra-peritoneum twice a week. After 4 weeks, all mice were sacrificed and tumor tissue was collected. The tissue was stained with hematoxylin and eosin and histological evaluation was conducted by blindly pathologist. Area of necrosis and vascular change in tumor tissue was calculated using the lasso tool to encircle the area in ZEN 2011 Imaging Software. Results: Both ginsenoside Rh2 and Rg5 induced cell necrosis in hepatocellular carcinoma (HCC) cell lines, and more necrosis occurred in 2D models. The expression of cleaved PARP protein was increased in both 2D and 3D cells with exposure to ginsenoside Rh2 and Rg5. The hepatocellular carcinoma was confirmed in hepatoma mouse models by H&E stain. Increased necrosis and telangiectasia were observed in mice treated with sorafenib, Rh2, and Rg5 compared to control mouse. Conclusions: Our findings provide insight into the use of xenograft mouse as models of HCC and ginsenoside Rh2 & Rg5 might be a potential treatment candidate of liver cancer.