Publications (18)59.38 Total impact
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Article: Initial Experience of Single-port Laparoscopic Surgery for Sigmoid Colon Cancer.
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ABSTRACT: BACKGROUND: Single-port laparoscopic surgery has attracted attention in the field of minimally invasive colorectal surgery. We hypothesized that an experienced laparoscopic surgeon could perform single-port surgery for colon cancer eligible for conventional laparoscopic anterior resection. Our aim was to analyze our initial experience and immediate surgical outcomes of single-port anterior resection. METHODS: A total of 37 consecutive patients with presumed sigmoid colonic cancer underwent single-port anterior resection with standard laparoscopic instruments between May 2009 and June 2010. Each operation was performed by one of two experienced colorectal surgeons. A cohort of patients who had undergone conventional laparoscopic surgery (CLS) for the same duration a year earlier (August 2007 to September 2008) was used as a historical control. Patient demographics and perioperative outcomes were analyzed and compared with those of CLS. RESULTS: There were no significant differences in mean estimated blood loss, mean length of the resection margin, or morbidity between the two groups, but operative time for the single-port group was significantly shorter (118 ± 41 vs 140 ± 42 min; p = 0.017). Single-port laparoscopic surgery was successfully performed in 78.4 % (29/37) of the patients treated in 2010, and CLS was successfully completed in all of the patients treated the previous year (p = 0.000). The main causes of single-port surgery failure were adhesion and tumor location. CONCLUSIONS: Single-port anterior resection is a feasible and safe procedure with immediate outcomes comparable to those of conventional laparoscopy. Further studies are required to determine the feasibility of single-port surgery for colonic tumors outside the sigmoid colon and the long-term outcome.World Journal of Surgery 12/2012; · 2.36 Impact Factor -
Article: Present condition analysis of physician assistant in Korea.
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ABSTRACT: This study intended to identify the need for the legalization and development of a systematic program for physician assistants (PAs) by understanding the actual state of PA operation in hospitals. In 114 hospitals assigned as resident training hospitals for surgery, a survey was conducted on the personnel working as PAs in those hospitals; the survey included general personal information, working conditions, training time, and satisfaction. A total of 192 PAs in surgery at 35 hospitals responded to the survey. The types of PAs are Surgical Assistant, Clinical Physician Assistant, Wound Ostomy Care Nurse, Coordinator, and Clinical Research Coordinator. Types of work PAs preformed are surgical assistance, wound dressing, educating patients, overlooking consultation, doing paper works, writing operation records, and confirming examination results which were ordered. The satisfaction level for the position which PAs hold were 29.1% and and satisfaction level which doctors see towards PA was 15%. The role and the job descriptions of PAs are not clear cut, there are many discrepancies among hospitals we studied. As a result, legalization and the implementation of standardized role of PAs will lead to increase level of satisfactions in the work force and the quality of work which PAs perform will be greater.Journal of Korean medical science 09/2012; 27(9):981-6. · 0.84 Impact Factor -
Article: Reduced Raf-1 kinase inhibitor protein expression predicts less favorable outcomes in patients with hepatic colorectal metastasis.
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ABSTRACT: Reduced expression of Raf-1 kinase inhibitor protein (RKIP) has been documented in a number of human malignancies, including colorectal carcinoma (CRC). However, despite the importance of hepatic colorectal metastasis (HCM) for the prognosis of CRC patients, no studies have been conducted regarding RKIP expression in HCM tissues or its prognostic significance. The aim of this study was to clarify the relationship between reduced RKIP expression and HCM and to identify independent predictors for recurrent HCM, which will ultimately help identify patients at high risk of developing metastatic recurrence. An immunohistochemical study of RKIP expression was performed using primary CRC and/or corresponding HCM tissue samples obtained from 117 patients. Forty-nine of these patients did not harbor HCM and 68 harbored HCM. RKIP expression was reduced in 24.5% (12/49) of CRCs without HCM, 47.1% (32/68) of CRCs with HCM and 67.6% (46/68) of HCM. This distribution of RKIP downregulation was statistically significant. RKIP expression was found to independently predict recurrent HCM, with a higher relative risk (6.661) compared to that of nodal metastasis (4.690). A reduction of RKIP expression in HCM was a significant predictor of poor prognosis. The median survival of patients with reduced RKIP expression was 35 months, compared with more than 10 years in patients with positive RKIP expression. Multivariate survival analysis demonstrated that RKIP expression in HCM was an independent predictor of overall survival, with a hazard ratio of 5.161, a value comparable to the risk associated with advanced TNM stage (5.247). We demonstrated that a reduction of RKIP expression in HCM had an independent predictive value for metastatic recurrence and less favorable clinical outcomes in patients with HCM. Our results strongly suggest that patients harboring HCM with reduced RKIP expression require careful monitoring after hepatic resection to detect potentially resectable metastatic recurrences.Oncology Reports 05/2012; 28(1):161-71. · 1.84 Impact Factor -
Article: Epigenetic alteration of PRKCDBP in colorectal cancers and its implication in tumor cell resistance to TNFα-induced apoptosis.
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ABSTRACT: PRKCDBP is a putative tumor suppressor in which alteration has been observed in several human cancers. We investigated expression and function of PRKCDBP in colorectal cells and tissues to explore its candidacy as a suppressor in colorectal tumorigenesis. Expression and methylation status of PRKCDBP and its effect on tumor growth were evaluated. Transcriptional regulation by NF-κB signaling was defined by luciferase reporter and chromatin immunoprecipitation assays. PRKCDBP expression was hardly detectable in 29 of 80 (36%) primary tumors and 11 of 19 (58%) cell lines, and its alteration correlated with tumor stage and grade. Promoter hypermethylation was commonly found in cancers. PRKCDBP expression induced the G(1) cell-cycle arrest and increased cellular sensitivity to various apoptotic stresses. PRKCDBP was induced by TNFα, and its level correlated with tumor cell sensitivity to TNFα-induced apoptosis. PRKCDBP induction by TNFα was disrupted by blocking NF-κB signaling while it was enhanced by RelA transfection. The PRKCDBP promoter activity was increased in response to TNFα, and this response was abolished by disruption of a κB site in the promoter. PRKCDBP delayed the formation and growth of xenograft tumors and improved tumor response to TNFα-induced apoptosis. PRKCDBP is a proapoptotic tumor suppressor which is commonly altered in colorectal cancer by promoter hypermethylation, and its gene transcription is directly activated by NF-κB in response to TNFα. This suggests that PRKCDBP inactivation may contribute to tumor progression by reducing cellular sensitivity to TNFα and other stresses, particularly under chronic inflammatory microenvironment.Clinical Cancer Research 12/2011; 17(24):7551-62. · 7.74 Impact Factor -
Article: Status and prospect of workforce requirement for surgery in republic of Korea.
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ABSTRACT: In order to prepare long-term alternatives to surgical residency training and workforce policies in Korea, objective data are needed; in addition, determination of the status of surgical procedures being performed is also needed. Cases of surgeries performed by board-certified Korean surgeons for 1 year, from July 2009 to June 2010 were reviewed and analyzed. Variation of the last five years was also investigated against the number of surgery cases of the same item and for data on status of population, medical institutions, and surgeons. Difficulty in distribution of a given surgery varied according to the classification of medical institution types, and performance of highly difficult surgeries occurred more in tertiary hospitals. The number of surgeries has increased over the last 5 years (28.1%). The number of surgeries among elderly patients (41.5%), high difficulty (41.8%), and tertiary hospitals (34.9%) has especially increased. There has been no increase in the number of diagnosis related group claim cases for the last 5 years (-0.8%). 43.3% of surgeons working at private clinics in Korea did not present surgery as an indicating item of their clinics. While the demand for surgeons in high risk and highly difficult surgeries is continuously increasing, stagnation is expected in the traditional area. Considering the proportion and current status of surgeons working at private clinics, the need for a realistic reduction in the quota of surgical residents and reconsideration of personnel policies is raised.Journal of the Korean Surgical Society. 12/2011; 81(6):363-73. -
Article: The epidemiology and cost of surgical site infections in Korea: a systematic review.
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ABSTRACT: To conduct a systematic literature review of the epidemiological and economic burden of surgical site infection (SSI) in Korea. A search of the EMBASE, Medline and KoreaMed databases for English and Korean language publications was conducted. Searches for epidemiological and economic studies were conducted separately and limited to 1995 to 2010 to ensure the pertinence of the data. Twenty-six studies were included. The overall incidence of SSI in Korea was 2.0 to 9.7%. The National Nosocomial Infections Surveillance risk index was positively correlated with the risk of developing an SSI. Specific risk factors for SSI, identified through multivariate analyses included; diabetes, antibiotic prophylaxis and wound classification. SSIs were associated with increased hospitalisation cost, with each episode of SSI estimated to cost about an additional ₩2,000,000. A substantial portion of the increased cost was attributed to hospital room costs and the need for additional medication. Studies also found that post-operative stays for patients with SSIs were 5 to 20 days longer, while two studies reported that following cardiac surgery, patients with SSIs spent an additional 5 to 11 days in the intensive care unit, compared to patients without SSIs. Data from the included studies demonstrate that SSI represents a significant clinical and economic burden in Korea. Consequently, the identification of high-risk patient populations and the development of strategies aimed at reducing SSI may lead to cost-savings for the healthcare system.Journal of the Korean Surgical Society. 11/2011; 81(5):295-307. -
Article: Laparoscopic abdominoperineal resection for rectal cancer in a patient with situs inversus totalis.
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ABSTRACT: Situs inversus totalis (SIT) is a very rare condition. Laparoscopic surgery in a patient with SIT is difficult because the surgeon's dexterity is compromised during the procedure, and the patient's anatomy is the mirror image of normal. We present a SIT patient who underwent laparoscopic abdominoperineal resection for rectal cancer. The detailed operative procedures and trocar placement considerations are described.Surgical laparoscopy, endoscopy & percutaneous techniques 04/2011; 21(2):e87-90. · 1.23 Impact Factor -
Article: Filiform polyposis associated with sigmoid diverticulitis in a patient without inflammatory bowel disease.
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ABSTRACT: Filiform polyposis (FP) of the colon is an uncommon entity that is occasionally encountered in patients with inflammatory bowel disease (IBD). FP is morphologically characterized by multiple slender worm-like projections consisting of submucosal cores lined with normal mucosa. To date, only two cases of FP have been reported in patients with inflammatory conditions of the gastrointestinal tract other than ulcerative colitis or Crohn's disease. We report an additional case of FP occurring in an 83-year-old man with no history of IBD. The patient underwent anterior resection of the sigmoid colon for perforated diverticulitis. Around the diverticular orifice, localized FP involving a 13-cm colonic segment was observed. The filiform polyps consisted of submucosal fibrovascular cores lined with normal mucosa without epithelial dysplasia. To our knowledge, this is the first reported case of FP associated with colonic diverticulitis in a patient without IBD.Journal of Crohn s and Colitis 12/2010; 4(6):671-3. · 2.57 Impact Factor -
Article: Epigenetic inactivation of the NORE1 gene correlates with malignant progression of colorectal tumors.
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ABSTRACT: NORE1 (RASSF5) is a newly described member of the RASSF family with Ras effector function. NORE1 expression is frequently inactivated by aberrant promoter hypermethylation in many human cancers, suggesting that NORE1 might be a putative tumor suppressor. However, expression and mutation status of NORE1 and its implication in colorectal tumorigenesis has not been evaluated. Expression, mutation, and methylation status of NORE1A and NORE1B in 10 cancer cell lines and 80 primary tumors were characterized by quantitative PCR, SSCP, and bisulfite DNA sequencing analyses. Effect of NORE1A and NORE1B expression on tumor cell growth was evaluated using cell number counting, flow cytometry, and colony formation assays. Expression of NORE1A and NORE1B transcript was easily detectable in all normal colonic epithelial tissues, but substantially decreased in 7 (70%) and 4 (40%) of 10 cancer cell lines and 31 (38.8%) and 25 (31.3%) of 80 primary carcinoma tissues, respectively. Moreover, 46 (57.6%) and 38 (47.5%) of 80 matched tissue sets exhibited tumor-specific reduction of NORE1A and NORE1B, respectively. Abnormal reduction of NORE1 was more commonly observed in advanced stage and high grade tumors compared to early and low grade tumors. While somatic mutations of the gene were not identified, its expression was re-activated in all low expressor cells after treatment with the demethylating agent 5-aza-dC. Bisulfite DNA sequencing analysis of 31 CpG sites within the promoter region demonstrated that abnormal reduction of NORE1A is tightly associated with promoter CpG sites hypermethylation. Moreover, transient expression and siRNA-mediated knockdown assays revealed that both NORE1A and NORE1B decrease cellular growth and colony forming ability of tumor cells and enhance tumor cell response to apoptotic stress. Our data indicate that epigenetic inactivation of NORE1 due to aberrant promoter hypermethylation is a frequent event in colorectal tumorigenesis and might be implicated in the malignant progression of colorectal tumors.BMC Cancer 10/2010; 10:577. · 3.01 Impact Factor -
Article: Endo-satinsky clamp for rectal transection during laparoscopic total mesorectal excision.
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ABSTRACT: We describe a technique of intracorporeal rectal transection using an endo-Satinsky clamp during laparoscopic total mesorectal excision. We use an abdominal approach through 5 trocars. The rectum and mesorectum are mobilized completely. A flexible trocar is placed at the site of a 12-mm right lower abdominal port after the trocar originally placed there is pulled out. The 12-mm trocar originally placed in the right lower abdomen is moved to the suprapubic site, in which a Pfannenstiel incision is anticipated. The endo-Satinsky clamp is inserted through the flexible trocar, and the rectum is grasped with the endo-Satinsky clamp just above the anticipated point of transection. The endostapler is introduced through the 12-mm suprapubic port and is positioned just distal to the clamp. The rectum is then transected. The transected bowel is resected extracorporeally. Anastomosis is completed intracorporeally by use of a double-stapling technique. From February 2007 to March 2009, we performed low anterior resection with use of the endo-Satinsky clamp for 11 patients with rectal cancer (laparoscopic, 10 patients; robot-assisted, 1 patient). There were no operative complications or deaths. Mean operation time was 179.5 minutes (range, 120-265 min). The average number of cartridges used for rectal transection was 1.6 per patient. The endo-Satinsky clamp is a useful device for rectal transection and irrigation. The use of this device makes it easier to place an endostapler just distal to the clamp and to transect the rectum in a more appropriate position.Diseases of the Colon & Rectum 03/2010; 53(3):355-9. · 3.13 Impact Factor -
Article: Single port laparoscopic right hemicolectomy with D3 dissection for advanced colon cancer.
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ABSTRACT: We report the first case of single port laparoscopic right hemicolectomy for advanced colon cancer. An abdominal 3 cm length incision was made via the umbilicus. A small wound retractor and a surgical glove were used as a single port. All soft tissue anterior to the superior mesenteric vein was completely removed and D3 lymph node dissection was achieved. The total operative time was 180 min with minimal blood loss (< 50 mL). The size of the tumor was 5 cm x 3 cm and its tumor stage was T3N0. Sixty-nine lymph nodes were harvested and none were positive. We believe that single port surgery for colon cancer is a feasible and safe procedure with surgical results comparable to conventional laparoscopic procedures.World Journal of Gastroenterology 01/2010; 16(2):275-8. · 2.47 Impact Factor -
Article: Image-guided conservative management of right colonic diverticulitis.
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ABSTRACT: To study the clinical outcomes of medical therapy in patients with right colonic diverticulitis. The records of 189 patients with right colonic diverticulitis which was finally diagnosed by computed tomography, ultrasonography, or operative findings were retrospectively reviewed. Of the 189 patients hospitalized for right colonic diverticulitis, the stages of diverticulitis by a modified Hinchey classification were 26 patients (13.8%) in stage 0, 139 patients (73.5%) in stage Ia, 23 patients (12.2%) in stage Ib, and 1 patient (0.5%) in stage III. Medical therapy was undertaken in 185 of 189 patients (97.9%). One hundred and eighty three of 185 patients were successfully treated with bowel rest and antibiotics. Two patients in stage Ib required a resection or surgical drainage because of an inadequate response to conservative treatment. Recurrent diverticulitis developed in 15 of 183 patients (8.2%) who responded to medical therapy. All 15 patients who suffered a second attack had uncomplicated diverticulitis, and were successfully treated with medical therapy. Our results indicate that right colonic diverticulitis is essentially benign and image-guided conservative treatment is primarily required.World Journal of Gastroenterology 12/2009; 15(46):5838-42. · 2.47 Impact Factor -
Article: Small bowel evisceration by rupture of prolapsed loop ileostomy.
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ABSTRACT: Abstract The formation of a stoma is one of the easiest bowel procedures but many patients suffer from stoma-related complications. Stomal prolapse may develop in any type of abdominal stoma. Most can be reduced manually and managed conservatively. However, we experienced a case of small bowel evisceration following rupture of a prolapsed loop ileostomy during attempted manual reduction. When gentle reduction is unsuccessful, clinicians should avoid exerting greater pressure and consider proceeding directly to surgery.Colorectal Disease 05/2009; 12(6):603-4. · 2.93 Impact Factor -
Article: NF-kappaB activates transcription of the RNA-binding factor HuR, via PI3K-AKT signaling, to promote gastric tumorigenesis.
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ABSTRACT: HuR is a RNA-binding factor whose expression is commonly upregulated in some human tumor types. We explored the molecular mechanism underlying HuR elevation and its role in gastric cancer tumorigenesis. HuR expression and subcellular localization were determined by polymerase chain reaction, immunoblot, and immunohistochemical analyses. Its effect on tumor growth was characterized using flow cytometry, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling, and soft agar analyses. Luciferase reporter, chromatin immunoprecipitation, and electrophoretic mobility shift assays were used to measure transcriptional activation by nuclear factor kappaB (NF-kappaB) signaling. Compared with normal gastric tissues, HuR was expressed at higher levels in gastric tumors, particularly in advanced versus early tumors; this increase was associated with enhanced cytoplasmic translocation of HuR. HuR overexpression increased proliferation of tumor cells, activating the G(1) to S transition of the cell cycle, DNA synthesis, and anchorage-independent growth. Small interfering RNA-mediated knockdown of HuR expression reduced tumor cell proliferation and response to apoptotic stimuli. No genetic or epigenetic alterations of HuR were observed in gastric tumor cell lines or primary tumors; overexpression depended on phosphatidylinositol 3-kinase/AKT signaling and NF-kappaB activity. AKT activation increased p65/RelA binding to a putative NF-kappaB binding site in the HuR promoter, the stability of HuR target transcripts, and the cytoplasmic import of HuR. HuR is a direct transcription target of NF-kappaB; its activation in gastric cancer cell lines depends on phosphatidylinositol 3-kinase/AKT signaling. HuR activation by this pathway has proliferative and antiapoptotic effects on gastric cancer cells.Gastroenterology 09/2008; 135(6):2030-42, 2042.e1-3. · 11.68 Impact Factor -
Article: Clinical significance of lymph node micrometastasis in stage I and II colon cancer.
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ABSTRACT: A 25% rate of recurrence after performing complete resection in node-negative colon cancer patients suggests that their nodal staging is frequently suboptimal. Moreover, the value of occult cancer cells in tumor-free lymph nodes still remains uncertain. The authors evaluated the prognostic significance of the pathologic parameters, including the lymph node occult disease (micrometastases) detected by immunohistochemistry, in patients with node-negative colon cancer. The study included 160 patients with curatively resected stage I or II colon cancer and they were without rectal cancer. 2852 lymph nodes were re-examined by re-do hematoxylin and eosin (H-E) staining and immunohistochemical staining. The detection rates were compared with the clinicopathologic characteristics and with the cancer-specific survival. Occult metastases were detected in 8 patients (5%). However, no clinicopathologic parameter was found to be correlated with the presence of micrometastasis. Twenty patients developed recurrence at a median follow-up of 45.7 months: 14 died of colon cancer and 9 died from noncancer-related causes. Univariate analysis showed that lymphatic invasion and the number of retrieved lymph nodes significantly influenced survival, and multivariate analysis revealed that the stage, the number of retrieved lymph nodes and lymphatic invasion were independently related to the prognosis. Inadequate lymph node retrieval and lymphatic invasion were found to be associated with a poorer outcome for node-negative colon cancer patients. The presence of immunostained tumors cells in pN0 lymph nodes was found to have no significant effect on survival, but these tumor were identified by re-do H-E staining. Maximal attention should be paid to the total number of lymph nodes that are retrieved during surgery for colon cancer patients.Cancer Research and Treatment 07/2008; 40(2):75-80. -
Article: Frequent epigenetic inactivation of hSRBC in gastric cancer and its implication in attenuated p53 response to stresses.
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ABSTRACT: hSRBC is a putative tumor suppressor located at 11p15.4, at which frequent genomic loss has been observed in several human malignancies. To explore the candidacy of hSRBC as a suppressor of gastric tumorigenesis, we analyzed the expression and mutation status of hSRBC in gastric tissues and cell lines. hSRBC transcript was expressed in all normal and benign tumor tissues examined, but undetectable or very low in 73% (11/15) cancer cell lines and 41% (46/111) primary tumors. Loss or reduction of hSRBC expression was tumor-specific and correlated with stage and grade of tumors. While allelic loss or somatic mutations of the gene were infrequent, its expression was restored in tumor cells by 5-aza-2'-deoxycytidine treatment and aberrant hypermethylation of 23 CpG sites in the promoter region showed a tight association with altered expression. Transient or stable expression of hSRBC led to a G(1) cell cycle arrest and apoptosis of tumor cells, and strongly suppresses colony forming ability and xenograft tumor growth. In addition, hSRBC elevated apoptotic sensitivity of tumor cells to genotoxic agents, such as 5-FU, etoposide and ultraviolet. Interestingly, hSRBC increased the protein stability of p53 and expression of p53 target genes, such as p21(Waf1), PUMA and NOXA, while hSRBC-mediated cell cycle arrest and apoptosis were abolished by blockade of p53 function. Our findings suggest that hSRBC is a novel tumor suppressor whose epigenetic inactivation contributes to the malignant progression of gastric tumors, in part, through attenuated p53 response to stresses.International Journal of Cancer 05/2008; 122(7):1573-84. · 5.44 Impact Factor -
Article: Frequent alteration of XAF1 in human colorectal cancers: implication for tumor cell resistance to apoptotic stresses.
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ABSTRACT: X-linked inhibitor of apoptosis protein-associated factor 1 (XAF1) is a candidate tumor suppressor located at the chromosome 17p13 region, but the molecular basis underlying its inactivation in human tumors and growth-inhibiting function has not been well defined. We explored the candidacy of XAF1 as a suppressor in colorectal tumorigenesis. XAF1 expression was characterized by polymerase chain reaction-based cloning, isoform-specific polymerase chain reaction, ribonuclease protection, and immunoblot assays. Allelic loss of the gene was evaluated by loss of heterozygosity (LOH) assay, and promoter CG dinucleotide (CpG) site methylation was determined using bisulfite sequencing. The effect of XAF1 on tumor growth was examined using flow cytometry, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling, colony formation, and viability assays. Expression of 5 XAF1 variants including 2 novel transcripts was down-regulated concomitantly in 11 of 20 (55%) cell lines and 26 of 65 (40%) primary tumors. XAF1 reduction was tumor-specific and showed a correlation with advanced stage and high grade of tumor. LOH of the gene was found in 12 of 33 (36%) tumors. Promoter CpG site methylation was observed frequently in both cell lines and tumor tissues including many LOH tumors, suggesting that biallelic inactivation of XAF1 might be common in colorectal cancers. XAF1 expression suppressed tumor cell growth and enhanced cellular response to various apoptotic stimuli, such as 5-fluorouracil, etoposide, H(2)O(2), gamma-irradiation, ultraviolet, and tumor necrosis factor-alpha, whereas knockdown of its expression protected cells from the stresses. Genetic and epigenetic alteration of XAF1 is a common event in colorectal tumorigenesis and contributes to the malignant tumor progression by providing survival advantages for tumor cells under various stress conditions.Gastroenterology 06/2007; 132(7):2459-77. · 11.68 Impact Factor -
Article: [Frequent epigenetic inactivation of XAF1 by promotor hypermethylation in human colon cancers].
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ABSTRACT: X-linked inhibitor of apoptosis (XIAP) is the most potent member of the IAP family that exerts antiapoptotic effects. Recently, XIAP-associated factor 1 (XAF1) and two mitochondrial proteins, Smac/ DIABLO and HtrA2, have been identified to negatively regulate the caspase-inhibiting activity of XIAP. We explored the candidacy of XAF1, Smac/DIABLO and HtrA2 as a tumor suppressor in colonic carcinogenesis. Expression and mutation status of the genes in 10 colorectal carcinoma cell lines and 40 primary tumors were examined by quantitative PCR analysis. XAF1 transcript was not expressed or present at extremely low levels in 60% (6/10) of cancer cell lines whereas Smac/DIABLO and HtrA2 are normally expressed in all cell lines examined. Tumor-specific loss or reduction of XAF1 was also found in 35% (14/40) of matched tissue sets obtained from the same patients. XAF1 transcript was reactivated in all the low expressor cell lines by treatment with the demethylating agent 5-aza-2'-deoxycytidine. Moreover, bisulfite DNA sequencing analysis for 34 CpG sites in the promoter region revealed a strong association between hypermethylation and gene silencing. Restoration of XAF1 expression resulted in enhanced apoptotic response to etoposide and 5-flurouracil, whereas knockdown of XAF1 expression by siRNA transfection significantly inhibited chemotherapeutic drug-induced apoptosis. XAF1 undergoes epigenetic gene silencing in a considerable proportion of human colon cancers by aberrant promoter hypermethylation, suggesting that XAF1 inactivation might be implicated in colonic tumorigenesis.The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi 05/2005; 45(4):285-93.
Top co-authors
Top Journals
Institutions
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2009–2011
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Kyung Hee University Medical Center
Seoul, Seoul, South Korea
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2007–2011
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Korea University
Seoul, Seoul, South Korea
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2008–2010
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Kyung Hee University
- Department of Medicine
Seoul, Seoul, South Korea
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