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1.  Long-Term Outcomes of Cytomegalovirus Reactivation in Patients with Moderate to Severe Ulcerative Colitis: A Multicenter Study 
Gut and Liver  2014;8(6):643-647.
Cytomegalovirus (CMV) reactivations are frequently observed in patients with active ulcerative colitis (UC), and ganciclovir therapy is effective in patients with steroid-refractory UC. This study aimed to determine the long-term outcomes of CMV reactivation and the long-term therapeutic efficacy of ganciclovir treatment.
This retrospective multicenter study included a cohort of 72 patients with moderate-to-severe UC who were evaluated for CMV reactivation at the time of their initial UC flare. Colectomy, disease relapse, and the recurrence rate of CMV reactivation were investigated.
The mean duration of follow-up for the 72 patients was 43.16±19.78 months (range, 1 to 67 months). The cumulative colectomy (log-rank, p=0.025) and disease flare-up rates (log-rank, p=0.048) were significantly higher in the CMV-positive group. Of the 11 patients who were successfully treated with ganciclovir in the initial treatment, three patients (27.3%) experienced CMV reactivation, and six patients (54.5%) experienced poor outcomes, such as the need for colectomy or a steroid-dependent state.
The patients who had CMV-reactivated UC showed poor outcomes at the long-term follow-up, and the long-term efficacy of ganciclovir therapy was marginal. Careful assessment is necessary for patients who exhibit evidence of CMV reactivation.
PMCID: PMC4215451  PMID: 25368753
Colitis; ulcerative; Cytomegalovirus; Ganciclovir; Colectomy
2.  Colon Cancer Screening and Surveillance in Inflammatory Bowel Disease 
Clinical Endoscopy  2014;47(6):509-515.
Patients with inflammatory bowel disease (IBD) have an increased risk of developing colorectal cancer (CRC). Accordingly, the duration and anatomic extent of the disease have been known to affect the development of IBD-related CRC. When CRC occurs in patients with IBD, unlike in sporadic CRC, it is difficult to detect the lesions because of mucosal changes caused by inflammation. In addition, the tumor types vary with ill-circumscribed lesions, and the cancer is difficult to diagnose and remedy at an early stage. For the diagnosis of CRC in patients with IBD, screening endoscopy is recommended 8 to 10 years after the IBD diagnosis, and surveillance colonoscopy is recommended every 1 to 2 years thereafter. The recent development of targeted biopsies using chromoendoscopy and relatively newer endoscopic techniques helps in the early diagnosis of CRC in patients with IBD. A total proctocolectomy is advisable when high-grade dysplasia or multifocal low-grade dysplasia is confirmed by screening endoscopy or surveillance colonoscopy or if a nonadenoma-like dysplasia-associated lesion or mass is detected. Currently, pharmacotherapies are being extensively studied as a way to prevent IBD-related CRC.
PMCID: PMC4260098  PMID: 25505716
Inflammatory bowel diseases; Colonic neoplasms; Surveillance colonoscopy; Chemoprevention
3.  Leptin and peroxisome proliferator-activated receptor γ expression in colorectal adenoma 
AIM: To investigate the expressions of leptin and peroxisome proliferator-activated receptor γ (PPARG) in relation to body mass index (BMI).
METHODS: We evaluated leptin and PPARG expression in 30 adenomas over 1 cm in size by immunohistochemical staining. In addition, clinicopathologic features including BMI were assessed.
RESULTS: PPARG and leptin expression showed a strong positive correlation (P = 0.035). The average BMI of the leptin-positive group was higher than that of the leptin-negative group (25.4 ± 3.4 kg/m2 vs 22.6 ± 2.4 kg/m2, P = 0.018), and leptin expression was significantly correlated with high BMI (P = 0.024). Leptin expression was more frequently observed in intermediate/high grade dysplasia than in low grade dysplasia (P = 0.030). However, PPARG expression was not correlated with BMI and grade of dysplasia.
CONCLUSION: BMI has influenced on the leptin expression of colorectal adenoma. The exact mechanism underlies the strong correlation between leptin and PPARG expression needs further study.
PMCID: PMC3280402  PMID: 22363123
Leptin; Peroxisome proliferator-activated receptor γ; Obesity; Body mass index; Colorectal adenoma
4.  Long-Term Clinical Outcome of Clostridium difficile Infection in Hospitalized Patients: A Single Center Study 
Intestinal Research  2014;12(4):299-305.
Antibiotic usage and increasingly aging populations have led to increased incidence of Clostridium difficile infection (CDI) in worldwide. Recent studies in Korea have also reported increasing CDI incidence; however, there have been no reports on the long-term outcomes of CDI. We therefore investigated the long-term clinical outcomes of patients with CDI, including delayed recurrence, associated risk factors and mortality.
Hospitalized patients diagnosed with CDI at Seoul Paik Hospital between January 2007 and December 2008 were included. Their medical records were retrospectively investigated. 'Delayed recurrence' was defined as a relapse 8 weeks after a successful initial treatment. Multivariate logistic regression analysis was performed to identify risk factors for the delayed recurrence. Kaplan-Meier curves were used to analyze mortality rates.
A total of 120 patients were enrolled; among them, 87 were followed-up for at least 1 year, with a mean follow-up period of 34.1±25.1 months. Delayed recurrence was observed in 17 patients (19.5%), and significant risk factors were age (over 70 years, P=0.049), nasogastric tube insertion (P=0.008), and proton pump inhibitor or H2-blocker treatments (P=0.028). The 12- and 24-month mortality rates were 24.6% and 32.5%, respectively. No deaths were directly attributed to CDI.
Delayed recurrence of CDI was not rare, occurring in 19.5% of the study population. Although CDI-related mortality was not reported, 2-year (32.5%) mortality rate of CDI patients implies that a CDI diagnosis may predict severe morbidity and poor prognosis of the underlying disease.
PMCID: PMC4214957  PMID: 25374496
Clostridium difficile; Recurrence; Mortality; Risk factors
5.  A Korean experience of the use of Boston Bowel Preparation Scale: A Valid and Reliable Instrument for Colonoscopy-Oriented Research 
Few bowel preparation scales have been validated. The Boston Bowel Preparation Scale (BBPS) is a novel bowel preparation scale in western countries. We validated the BBPS in Korean patients and assessed the relationship between the colon polyp detection rate and BBPS score.
Patients and Methods:
This study was a prospective, single-center trial. The BBPS is a 10-point scale that assesses bowel preparation after the completion of all cleansing maneuvers. We assessed three segment scores (the right side, transverse section, and left side) and total BBPS scores during screening colonoscopy. In addition, we compared the BBPS scores with clinically meaningful outcomes such as the polyp detection rate and colonoscope withdrawal times.
We enrolled 482 screening colonoscopies between January 2011 and January 2012. The mean (± standard deviation [SD]) BBPS score was 8.1 ± 1.1. Higher BBPS scores (≥8 vs <8) were associated with a higher polyp detection rate (44.9% vs. 33.0%, P = 0.042). The BBPS scores were inversely correlated with colonoscope withdrawal times (r = −0.167, P < 0.001).
The BBPS is a valid and reliable measure for assessing bowel preparation during colonoscopy in Korean patients. The polyp detection rate is higher in patients with higher BBPS scores than in those with lower BBPS scores during a colonoscopic procedure.
PMCID: PMC4131304  PMID: 25038207
Boston bowel preparation scale; bowel preparation; colonoscopy; polyp detection rate
6.  20(S)-Ginsenoside Rg3 is a novel inhibitor of autophagy and sensitizes hepatocellular carcinoma to doxorubicin 
Oncotarget  2014;5(12):4438-4451.
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. High mortality from HCC is mainly due to widespread prevalence and the lack of effective treatment, since systemic chemotherapy is ineffective, while the targeted agent Sorafenib extends median survival only briefly. The steroidal saponin 20(S)-ginsenoside Rg3 from Panax ginseng C.A. Meyer is proposed to chemosensitize to various therapeutic drugs through an unknown mechanism. Since autophagy often serves as cell survival mechanism in cancer cells exposed to chemotherapeutic agents, we examined the ability of Rg3 to inhibit autophagy and chemosensitize HCC cell lines to doxorubicin in vitro. We show that Rg3 inhibits late stage autophagy, possibly through changes in gene expression. Doxorubicin-induced autophagy plays a protective role in HCC cells, and therefore Rg3 treatment synergizes with doxorubicin to kill HCC cell lines, but the combination is relatively nontoxic in normal liver cells. In addition, Rg3 was well-tolerated in mice and synergized with doxorubicin to inhibit tumor growth in HCC xenografts in vivo. Since novel in vivo inhibitors of autophagy are desirable for clinical use, we propose that Rg3 is such a compound, and that combination therapy with classical chemotherapeutic drugs may represent an effective therapeutic strategy for HCC treatment.
PMCID: PMC4147336  PMID: 24970805
Rg3; autophagy; HCC; doxorubicin; cell death
8.  What is the Important Issue to Prevent the Postoperative Crohn's Disease? 
Intestinal Research  2014;12(2):85-86.
PMCID: PMC4204710  PMID: 25349572
9.  Mycobacterium ulcerans infection as a cause of chronic diarrhea in an AIDS patient: A case report 
Chronic diarrhea is one of the most frequent gastro-intestinal manifestations in acquired immunodeficiency syndrome (AIDS). Protozoa and nontuberculous mycobacteria (NTM) are opportunistic pathogens that can easily infect these patients. Among the NTM, Mycobacterium avium complex (MAC) is the most frequently observed pathogen in HIV-infected patients. However, NTMs other than MAC have not been reported as a gastrointestinal pathogen as yet. We present a case of chronic diarrhea in an AIDS patient in whom Mycobacterium ulcerans and cryptosporidium co-infection is evidenced from colonic tissue.
PMCID: PMC2684015  PMID: 18205278
Mycobacterium ulcerans; Cryptosporidium; HIV; Chronic diarrhea
10.  Successful Treatment of Postoperative Fistula with Infliximab in a Patient with Crohn's Disease 
Intestinal Research  2014;12(1):74-77.
Nearly 80% of patients with Crohn's disease (CD) require surgical treatment for complications or failure of medical management. We managed a 31-year-old man with CD who presented with a post-operative fistula. The patient had undergone surgery due to multiple strictures and a fistula. However, a new fistula developed that connected to the intraperitoneal abscess. Intravenous antibiotics were started and multiple percutaneous drainage tubes were inserted to treat the abdominal abscess. However, the amount of drainage was consistently high, even one month after the operation. To treat the postoperative fistula, 5 mg/kg of infliximab was started, and the amount of drainage decreased dramatically to less than 10 cc a day. Some studies have reported that infliximab decreases the recurrence of CD after surgery. The effect of infliximab on post-operative fistulas in patients with CD has not been sufficiently studied. Our results indicated that the use of infliximab to treat post-operative fistula should be explored further in future clinical studies.
PMCID: PMC4204687  PMID: 25349568
Crohn's disease; Fistula; Infliximab
11.  Miniprobe Endoscopic Ultrasonography Has Limitations in Determining the T Stage in Early Colorectal Cancer 
Gut and Liver  2013;7(2):163-168.
Mini-probe endoscopic ultrasonography (mEUS) is a useful diagnostic tool for accurate assessment of tumor invasion. The aim of this study was to estimate the accuracy of mEUS in patients with early colorectal cancer (ECC).
Ninety lesions of ECC underwent mEUS for pre-treatment staging. We divided the lesions into either the mucosal group or the submucosal group according to the mEUS findings. The histological results of the specimens were compared with the mEUS findings.
The overall accuracy for assessing the depth of tumor invasion (T stage) was 84.4% (76/90). The accuracy of mEUS was significantly lower for submucosal lesions compared to mucosal lesions (p=0.003) and it was lower for large tumors (≥2 cm) (p=0.034). The odds ratios of large tumors and submucosal tumors affecting the accuracy of T staging were 3.46 (95% confidence interval [CI], 1.05 to 11.39) and 6.25 (95% CI, 1.85 to 25.14), respectively. When submucosal tumors were combined with large size, the odds ratio was 14.67 (95% CI, 1.46 to 146.96).
The overall accuracy of T stage determination with mEUS was considerably high in patients with ECC; however, the accuracy decreased when tumor size was >2 cm or the tumor had invaded the submucosal layer.
PMCID: PMC3607769  PMID: 23560151
Colorectal neoplasms; Endosonography
12.  MicroRNAs modulate the noncanonical NF-κB pathway by regulating IKKα expression during macrophage differentiation 
Nature immunology  2010;11(9):799-805.
MicroRNAs are key regulators in many biological processes including cell differentiation. Here we show that during human monocyte-macrophage differentiation, the expression of the microRNAs miR-223, miR-15a, and miR-16 is dramatically decreased, leading to increased expression of the serine-threonine kinase IKKα in macrophages. In macrophages, higher IKKα expression in conjunction with stabilization of the kinase NIK induces elevated p52. Due to low RelB transcription factor expression in untreated macrophages, high p52 expression represses the basal level of both canonical and noncanonical NF-κB target genes. However, proinflammatory stimuli in macrophages result in greater induction of noncanonical NF-κB target genes. Thus a decrease in certain microRNAs likely prevents macrophage hyperaction yet primes the macrophage for certain responses to proinflammatory stimuli.
PMCID: PMC2926307  PMID: 20711193
13.  Stone extraction balloon-guided repeat self-expanding metal stent placement 
Self-expanding metal stent (SEMS) placement offers safe and effective palliation in patients with upper gastrointestinal obstruction due to a malignancy. Well described complications of SEMS placement include tumor growth, obstruction, and stent migration. SEMS occlusions are treated by SEMS redeployment, argon plasma coagulation application, balloon dilation, and surgical bypass. At our center, we usually place the second SEMS into the first SEMS if there is complete occlusion by the tumor. We discovered an unusual complication during SEMS redeployment. The guidewire passed through the mesh of the first SEMS and caused the second SEMS to become entangled with the first SEMS. This led to the distortion and malfunction of the second SEMS, which worsened the gastric outlet obstruction. For lowering the risk of entanglement, we studied stone extraction balloon-guided repeat SEMS placement. This is the first report of a SEMS entangled by the mesh of the first SEMS and stone extraction balloon-guided repeat SEMS placement for lowering the risk of this complication.
PMCID: PMC2890952  PMID: 20572315
Gastric outlet obstruction; Self-expanding metal stent
14.  Clinical Characteristics of Colonic Diverticulosis in Korea: A Prospective Study 
The prevalence of colonic diverticulosis has been reported to be lower in Korea than in Western countries. This disease also shows markedly different characteristics in the Korean population. We describe herein a prospective investigation, based on colonoscopic examination, of the prevalence, clinical characteristics, and factors associated with colonic diverticulosis in Korea.
The prevalence of colonic diverticulosis has been reported to be lower in Korea than in Western countries. This disease also shows markedly different characteristics in the Korean population. We describe herein a prospective investigation, based on colonoscopic examination, of the prevalence, clinical characteristics, and factors associated with colonic diverticulosis in Korea.
The overall prevalence of colonic diverticulosis was 12.1% (103 / 848). The right side of the colon was involved in 84.5% of patients (87 / 103); patients with right side diverticula were, on average, younger than those with left side diverticulosis (p = 0.014). Multiple diverticula were observed in 60.2% (62 / 103) of patients. Age greater than 60 years, a high-fat diet, and alcohol consumption were significantly associated with the presence of colonic diverticulosis (p < 0.05).
The prevalence of colonic diverticulosis in Korea is increasing and is most commonly located in the right side of the colon. Further, old age and diet may affect the risk of development of this disease.
PMCID: PMC2880686  PMID: 20526386
Diverticulum, colon; Korea; Colonoscopy; Prospective studies
15.  Long-Term Clinical Outcomes of Korean Patient With Crohn's Disease Following Early Use of Infliximab 
Intestinal Research  2014;12(4):281-286.
Several recent studies have reported that the early use of infliximab (IFX) improves the prognosis of Crohn's disease (CD). However, no data are available from Asian populations, as the forementioned studies have all been conducted in Western countries. The aim of the current study was to evaluate the impact of early use of IFX on the prognosis of Korean patients with CD.
Patients with a diagnosis of CD established between July 1987 and January 2012 were investigated in 12 university hospitals in Korea. Because insurance coverage for IFX treatment began in August 2005, patients were assigned to either of 2 groups based on diagnosis date. The first group included patients diagnosed from July 1987 to December 2005, and the second from January 2006 to January 2012. We compared the cumulative probabilities of operation and reoperation between the two groups using the Kaplan-Meier method and a log-rank test.
Of the 721 patients investigated, 443 (61.4%) comprized the second group. Although the cumulative probabilities of immunosuppressant (P<0.001) and IFX use (P<0.001) after diagnosis were significantly higher in the second group, there were no significant differences in cumulative probabilities of operation (P=0.905) or reoperation (P=0.418) between two groups.
The early use of IFX did not reduce CD-related surgery requirements in Korean patients with CD. These study results suggest that the early use of IFX may have little impact on the clinical outcome of CD in Korean patients in the setting of a conventional step-up algorithm.
PMCID: PMC4214954  PMID: 25374493
Crohn disease; Infliximab; Prognosis
16.  Tracking Intravenous Adipose-Derived Mesenchymal Stem Cells in a Model of Elastase-Induced Emphysema 
Mesenchymal stem cells (MSCs) obtained from bone marrow or adipose tissue can successfully repair emphysematous animal lungs, which is a characteristic of chronic obstructive pulmonary disease. Here, we describe the cellular distribution of MSCs that were intravenously injected into mice with elastase-induced emphysema. The distributions were also compared to the distributions in control mice without emphysema.
We used fluorescence optical imaging with quantum dots (QDs) to track intravenously injected MSCs. In addition, we used a human Alu sequence-based real-time polymerase chain reaction method to assess the lungs, liver, kidney, and spleen in mice with elastase-induced emphysema and control mice at 1, 4, 24, 72, and 168 hours after MSCs injection.
The injected MSCs were detected with QD fluorescence at 1- and 4-hour postinjection, and the human Alu sequence was detected at 1-, 4- and 24-hour postinjection in control mice (lungs only). Injected MSCs remained more in mice with elastase-induced emphysema at 1, 4, and 24 hours after MSCs injection than the control lungs without emphysema.
In conclusion, our results show that injected MSCs were observed at 1 and 4 hours post injection and more MSCs remain in lungs with emphysema.
PMCID: PMC4192309  PMID: 25309606
Mesenchymal Stromal Cells; Emphysema; Cell Tracking; Injections, Intravenous
17.  A Milk Protein, Casein, as a Proliferation Promoting Factor in Prostate Cancer Cells 
Despite most epidemiologic studies reporting that an increase in milk intake affects the growth of prostate cancer, the results of experimental studies are not consistent. In this study, we investigated the proliferation of prostate cancer cells treated with casein, the main protein in milk.
Materials and Methods
Prostate cancer cells (LNCaP and PC3), lung cancer cells (A459), stomach cancer cells (SNU484), breast cancer cells (MCF7), immortalized human embryonic kidney cells (HEK293), and immortalized normal prostate cells (RWPE1) were treated with either 0.1 or 1 mg/mL of α-casein and total casein extracted from bovine milk. Treatments were carried out in serum-free media for 72 hours. The proliferation of each cell line was evaluated by an 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay.
α-Casein and total casein did not affect the proliferations of RWPE1, HEK293, A459, SNU484, MCF7, HEK293, or RWPE1 cells. However, PC3 cells treated with 1 mg/mL of α-casein and casein showed increased proliferation (228% and 166%, respectively), and the proliferation of LNCaP cells was also enhanced by 134% and 142%, respectively. The proliferation mechanism of α-casein in PC3 and LNCaP cells did not appear to be related to the induction of Insulin-like growth factor-1 (IGF-1), since the level of IGF-1 did not change upon the supplementation of casein.
The milk protein, casein, promotes the proliferation of prostate cancer cells such as PC3 and LNCaP.
PMCID: PMC4166373  PMID: 25237656
Caseins; Cell proliferation; Milk; Neoplasms; Prostate
18.  Release of Ca2+ from the endoplasmic reticulum and its subsequent influx into mitochondria trigger celastrol-induced paraptosis in cancer cells 
Oncotarget  2014;5(16):6816-6831.
Celastrol, a triterpene extracted from the Chinese “Thunder of God Vine”, is known to have anticancer activity, but its underlying mechanism is not completely understood. In this study, we show that celastrol kills several breast and colon cancer cell lines by induction of paraptosis, a cell death mode characterized by extensive vacuolization that arises via dilation of the endoplasmic reticulum (ER) and mitochondria. Celastrol treatment markedly increased mitochondrial Ca2+ levels and induced ER stress via proteasome inhibition in these cells. Both MCU (mitochondrial Ca2+ uniporter) knockdown and pretreatment with ruthenium red, an inhibitor of MCU, inhibited celastrol-induced mitochondrial Ca2+ uptake, dilation of mitochondria/ER, accumulation of poly-ubiquitinated proteins, and cell death in MDA-MB 435S cells. Inhibition of the IP3 receptor (IP3R) with 2-aminoethoxydiphenyl borate (2-APB) also effectively blocked celastrol-induced mitochondrial Ca2+ accumulation and subsequent paraptotic events. Collectively, our results show that the IP3R-mediated release of Ca2+ from the ER and its subsequent MCU-mediated influx into mitochondria critically contribute to celastrol-induced paraptosis in cancer cells.
PMCID: PMC4196165  PMID: 25149175
paraptosis; celastrol; endoplasmic reticulum; mitochondria; Ca2+
19.  Solitary Intra-abdominal Tuberculous Lymphadenopathy Mimicking Duodenal GIST 
Tuberculosis remains prevalent in developing countries and has recently re-emerged in the Western world. Intra-abdominal tuberculosis can mimic a variety of other abdominal disorders, and here we describe a patient with solitary tuberculous mesenteric lymphadenopathy mimicking duodenal gastrointestinal stromal tumor (GIST). A 22-year-old woman complained of epigastric discomfort and was presumed to have a duodenal GIST after an endoscopic examination and abdominal CT scan. However, exploratory laparotomy revealed an enlarged node penetrating the duodenal bulb, which was diagnosed histopathologically as tuberculous lymphadenitis. This case suggests that in regions with a high prevalence of tuberculosis, intra-abdominal tuberculosis is often mistaken as a malignant neoplasm. A high index of suspicion and the accurate nonsurgical diagnosis of intra-abdominal tuberculosis continues to be a challenge.
PMCID: PMC3891416  PMID: 15906957
Tuberculosis; Lymph Node; Gastrointestinal neoplasms
21.  The Effect of Infliximab on Patients with Ulcerative Colitis in Korea 
Intestinal Research  2014;12(3):214-220.
Infliximab was introduced recently as a rescue therapy for ulcerative colitis (UC) patients refractory to conventional treatments such as therapy with 5-amiono salicylic acids (5-ASA), immune modulators, and corticosteroids. However, there is insufficient data about its efficacy and safety in Korea.
From 7 tertiary referral hospitals, 33 patients who were treated with infliximab for moderate to severe (Mayo score 6-12) UC refractory to conventional treatment were recruited to this study. Clinical remission was defined as a total Mayo score of 2 or lower and every subscore less than 2. Partial response was defined as a decrease of Mayo score at least 3 points from baseline.
Twenty-three patients (69.7%) showed clinical remission and 29 patients (87.8%) showed partial response in the observation period. When the remission and non-remission groups were compared in univariate analysis, only a higher total Mayo score at base line (11.0±0.9 vs. 9.9±1.5; P=0.04) was related to remission. The remission maintenance rate decreased with time in the Kaplan-Meier analysis. Two patients experienced re-remission after the first remission followed by aggravation during infliximab treatment. Three patients stopped infliximab treatment owing to adverse events including rhabdomyolysis, pneumonia, and fever of unknown origin.
If there is no choice except surgery for UC patients refractory to conventional treatment, infliximab is an effective and relatively safe treatment option for these patients in Korea.
PMCID: PMC4204725  PMID: 25349595
Ulcerative colitis; Infliximab; Efficacy; Safety
22.  Restoration of ASC expression sensitizes colorectal cancer cells to genotoxic stress-induced caspase-independent cell death 
Cancer letters  2013;331(2):183-191.
Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), an essential component of the inflammasome complex, is frequently silenced by epigenetic methylation in many tumor cells. Here, we demonstrate that restoration of ASC expression in human colorectal cancer DLD-1 cells, in which ASC is silenced by aberrant methylation, potentiated cell death mediated by DNA damaging agent. Contrarily, ASC knockdown in HT-29 cells rendered cells less susceptible to etoposide toxicity. The increased susceptibility of ASC-expressing DLD-1 cells to genotoxic stress was independent of inflammasome or caspase activation, but partially dependent on mitochondrial ROS production and JNK activation. Thus, our data suggest that ASC expression in cancer cells is an important factor in determining their susceptibility to chemotherapy.
PMCID: PMC3627217  PMID: 23321501
ASC; DLD-1; Methylation; DNA damaging agent; Cell death
23.  Role of Regulatory T Cells in Transferable Immunological Tolerance to Bone Marrow Donor in Murine Mixed Chimerism Model 
Journal of Korean Medical Science  2013;28(12):1723-1728.
Constructing a bone marrow chimera prior to graft transplantation can induce donor-specific immune tolerance. Mixed chimerism containing hematopoietic cells of both recipient- and donor-origin has advantages attributed from low dose of total body irradiation. In this study, we explored the mechanism of mixed chimerism supplemented with depletion of Natural Killer cells. Mixed chimerism with C57BL/6 bone marrow cells was induced in recipient BALB/c mice which were given 450 cGy of γ-ray irradiation (n = 16). As revealed by reduced proliferation and cytokine production in mixed leukocyte reaction and ELISpot assay (24.6 vs 265.5), the allo-immune response to bone marrow donor was reduced. Furthermore, the induction of transferable immunological tolerance was confirmed by adoptive transfer and subsequent acceptance of C57BL/6 skin graft (n = 4). CD4+FoxP3+ regulatory T cells were increased in the recipient compartment of the mixed chimera (19.2% → 33.8%). This suggests that regulatory T cells may be therapeutically used for the induction of graft-specific tolerance by mixed chimerism.
PMCID: PMC3857366  PMID: 24339700
Bone Marrow Transplantation; Immune Tolerance; Natural Killer Cells; Regulatory T Cells
24.  High Rates of Detection of Respiratory Viruses in the Nasal Washes and Mucosae of Patients with Chronic Rhinosinusitis 
Journal of Clinical Microbiology  2013;51(3):979-984.
Respiratory viral infections are often implicated as triggers of chronic rhinosinusitis (CRS) flare-ups. However, there is a paucity of respiratory viral surveillance studies in CRS patients, and such studies could elucidate the potential role of viruses in promoting symptoms and aggravating mucosal inflammation. Therefore, a prospective case-control study was conducted to determine the prevalence of respiratory viruses in CRS patients and non-CRS controls. Nasal lavage fluids and turbinate epithelial cells were collected prospectively from 111 CRS patients and 50 controls. Multiplex PCR was used to identify common respiratory viruses in both sample types and the infection rate was compared between groups. Respiratory viruses were detected in 50.5% of lavage samples and in 64.0% of scraping samples from CRS patients. The overall infection rate was significantly different in CRS patients and controls (odds ratio, 2.9 in lavage and 4.1 in scraping samples). Multiple viral infections were detected more frequently in lavage samples from CRS patients than those from controls (P < 0.01; odds ratio, 7.7). Rhinovirus was the most prevalent virus and the only virus with a significantly different infection rate in CRS patients and controls in both samples (odds ratio, 3.2 in lavage and 3.4 in scraping samples). This study detected a higher prevalence of respiratory viruses in CRS patients than controls, suggesting that there may be significant associations between inflammation of CRS and respiratory viruses, particularly rhinovirus. Further studies should investigate the exact role of highly prevalent respiratory viruses in CRS patients during symptomatic aggravation and ongoing mucosal inflammation.
PMCID: PMC3592049  PMID: 23325817
25.  Photodynamic Therapy with Ablative Carbon Dioxide Fractional Laser for Treating Bowen Disease 
Annals of Dermatology  2013;25(3):335-339.
Topical photodynamic therapy (PDT) has been increasingly used to treat malignant skin tumors including the Bowen disease. However, patients could be displeased with the long incubation time required for conventional PDT.
We evaluated the efficacy and safety of PDT with a short incubation time of ablative CO2 fractional laser pretreatment for treating Bowen disease.
Ten patients were included. Just before applying the topical photosensitizer, all lesions were treated with ablative CO2 fractional laser, following the application of methyl aminolevulinate and irradiation with red light (Aktilite CL 128). Histological confirmation, rebiopsy, and clinical assessments were performed. Adverse events were also recorded.
Five of the ten (50%) lesions showed a complete response (CR) within three PDT sessions. After four treatment sessions, all lesions except one penile shaft lesion (90%) achieved clinical and histological CR or clinical CR only. The average number of treatments to CR was 3.70±1.70. The treatments showed favorable cosmetic outcomes and no serious adverse events.
The results suggest that pretreatment with an ablative fractional CO2 laser before PDT has similar treatment efficacy and requires a shorter photosensitizer incubation time compared with the conventional PDT method.
PMCID: PMC3756199  PMID: 24003277
Ablative carbon dioxide fractional laser; Bowen disease; Photodynamic therapy; Pretreatment

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