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1.  Chemopreventive drugs: Mechanisms via inhibition of cancer stem cells in colorectal cancer 
Recent epidemiological studies, basic research and clinical trials on colorectal cancer (CRC) prevention have helped identify candidates for effective chemopreventive drugs. However, because of the conflicting results of clinical trials or side effects, the effective use of chemopreventive drugs has not been generalized, except for patients with a high-risk for developing hereditary CRC. Advances in genetic and molecular technologies have highlighted the greater complexity of carcinogenesis, especially the heterogeneity of tumors. We need to target cells and processes that are critical to carcinogenesis for chemoprevention and treatment of advanced cancer. Recent research has shown that intestinal stem cells may serve an important role in tumor initiation and formation of cancer stem cells. Moreover, studies have shown that the tumor microenvironment may play additional roles in dedifferentiation, to enable tumor cells to take on stem cell features and promote the formation of tumorigenic stem cells. Therefore, early tumorigenic changes of stem cells and signals for dedifferentiation may be good targets for chemoprevention. In this review, I focus on cancer stem cells in colorectal carcinogenesis and the effect of major chemopreventive drugs on stem cell-related pathways.
PMCID: PMC3983440  PMID: 24744576
Colorectal cancer; Chemoprevention; Cancer stem cell; Carcinogenesis; Microenvironment
2.  Conventional endoscopic features are not sufficient to differentiate small, early colorectal cancer 
AIM: To evaluate the depth of invasion of small, early colorectal cancers (ECCs) using conventional endoscopic features.
METHODS: From January 2005 to September 2011, colonoscopy cohort showed that a total of 72 patients with small colorectal cancers with the size less than 20 mm underwent colonoscopy at the Yonsei University College of Medicine, Seoul, South Korea. Among them, 8 patients were excluded due to incomplete medical records. Finally, a total of 64 ECCs with submucosa (SM) invasion and size less than 20 mm were included. One hundred fifty-two adenomas with size less than 20 mm were included as controls. Nine endoscopic features, including seven morphological findings (i.e., loss of lobulation, excavation, demarcated and depressed areas, stalk swelling, fullness, fold convergence, and bleeding ulcers), pit patterns, and non-lifting signs, were evaluated retrospectively. All endoscopic features were evaluated by two experienced endoscopists who have each performed over 1000 colonoscopies annually for more than five years without knowledge of the histology.
RESULTS: Among the morphological findings, the size of deep submucosal cancers was bigger than that of superficial lesions (16.9 mm vs 12.3 mm, P < 0.001). Also, demarcated depressed areas, stalk swelling, and fullness were more common in deep SM cancers than in superficial tumors (demarcated depressed areas: 52.0% vs 15.7%, P < 0.001; stalk swelling: 100% vs 4.2%, P < 0.001; fullness: 25.0% vs 0%, P = 0.001). Among deep SM cancers, 96% of polyps showed invasive pit patterns, whereas 19.4% of superficial tumors showed invasive pit patterns (P < 0.001). A positive non-lifting sign was more common in deep SM cancers (85.0% vs 28.6%, P < 0.001). Diagnostic accuracy of invasive morphology, invasive pit patterns, and non-lifting signs for deep SM cancers were 71%, 82%, and 75%, respectively.
CONCLUSION: Conventional endoscopic findings were insufficient to discriminate small, deep SM cancers from superficial SM cancers by white light, standard colonoscopy.
PMCID: PMC4047345  PMID: 24914381
Colonoscopy; Colorectal neoplasms; Differential diagnosis
3.  The digital version of JPIS offers more than ever 
PMCID: PMC4050225  PMID: 24921052
4.  Clinical meaning of BRAF mutation in Korean patients with advanced colorectal cancer 
AIM: To evaluate the clinicopathological features of colorectal cancer (CRC) with a v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation and its molecular interaction with microsatellite instability (MSI) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) in patients with advanced CRCs.
METHODS: From October 2009 to December 2011, 141 patients with stage III (n = 51) or IV (n = 90) CRCs who were tested for the BRAF mutation at Severance Hospital were included. Among 141 patients, five were excluded due to follow-up loss. Therefore, 136 patients were included in the study. The clinicopathological data, MSI status, and KRAS/BRAF mutation status were reviewed retrospectively. In addition, to evaluating the value of BRAF mutation status, progression-free survival and overall survival in all patients were collected and compared between the BRAF wild-type group and BRAF mutation group.
RESULTS: Of 136 patients, 80 (58.8%) were male and the mean age was 59 years. BRAF and KRAS mutations were detected in 9.6% and 35.3% of patients, respectively. Only 4.3% of patients had MSI-high tumors and there were no MSI-high in tumors with a BRAF mutation. BRAF mutations tended to be more frequent in stage IV than in stage III (11.76% vs 5.88%, P = 0.370). Patients with a BRAF mutation had a lower incidence of KRAS mutation than those without (7.69% vs 38.21%, P = 0.033). Overall survival was significantly shorter in the BRAF mutation group than in the BRAF wild-type group both by univariate analysis (P = 0.041) and multivariate analysis (HR = 2.195; 95%CI: 1.039-4.640; P = 0.039), while progression-free survival was not different according to BRAF mutation status.
CONCLUSION: CRCs with a BRAF mutation have distinct molecular features and resulted in a poor prognosis in Korean patients with advanced CRC.
PMCID: PMC3989973  PMID: 24764675
BRAF; Colorectal cancer; Molecular features; Chemotherapy response; Prognosis
5.  Can't and Won't 
PMCID: PMC3999351  PMID: 24778897
6.  Concerns about maintenance of natural teeth and dental implants 
PMCID: PMC3945390  PMID: 24616826
7.  New Year's resolution in JPIS 
PMCID: PMC3891855  PMID: 24455436
8.  Intestinal Behçet’s disease appearing during treatment with adalimumab in a patient with ankylosing spondylitis 
Behçet’s disease (BD) is a chronic inflammatory disease affecting multiple organ systems, such as the skin, joints, blood vessels, central nervous system, and gastrointestinal tract. Intestinal BD is characterized by intestinal ulcerations and gastrointestinal symptoms. The medical treatment of intestinal BD includes corticosteroids and immunosupressants. There have been several reports of tumor necrosis factor-α (TNF-α) blockers being successful in treatment of refractory intestinal BD. Here, we report on a patient who was diagnosed with intestinal BD despite treatment with the fully humanized TNF-α blocker (adalimumab) for underlying ankylosing spondylitis. This patient achieved clinical remission and complete mucosal healing through the addition of a steroid and azathioprine to the adalimumab regimen.
PMCID: PMC3752577  PMID: 23983446
Intestinal Behçet’s disease; Tumor necrosis factor-α; Adalimumab
9.  Is one better than two? 
PMCID: PMC3769591  PMID: 24040565
10.  Compassionate ethics for clinics 
PMCID: PMC3651936  PMID: 23678386
11.  Risk and reward 
PMCID: PMC3596627  PMID: 23509670
12.  One day more 
PMCID: PMC3543932  PMID: 23336083
13.  Correlation between Soluble Triggering Receptor Expressed on Myeloid Cells-1 and Endoscopic Activity in Intestinal Behçet's Disease 
Yonsei Medical Journal  2014;55(4):960-966.
The serum levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) have recently been shown to be correlated highly with disease activity in patients with intestinal Behçet's disease (BD). However, it remains unclear whether sTREM-1 levels reflect endoscopic activity in intestinal BD. This study aimed to evaluate the correlation of sTREM-1 levels with endoscopic activity in intestinal BD.
Materials and Methods
A total of 84 patients with intestinal BD were enrolled. Endoscopic activity was compared with sTREM-1 levels as well as other laboratory findings, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).
sTREM-1 levels were significantly increased in intestinal BD patients compared with controls (37.98±27.09 pg/mL vs. 16.65±7.76 pg/mL, p=0.002), however, there was no difference between endoscopically quiescent and active diseases (43.53±24.95 pg/mL vs. 42.22±32.68 pg/mL, p=0.819). Moreover, serum sTREM-1 levels did not differ in terms of number, shape, depth, size, margin, or type of ulcer in patients with intestinal BD. However, mean ESR and CRP levels in patients with active disease were significantly higher than those in patients with quiescent disease (p=0.001, p<0.001, respectively). In addition, endoscopic activity scores for intestinal BD were correlated significantly with both CRP levels (γ=0.329) and ESR (γ=0.298), but not with sTREM-1 levels (γ=0.166).
Unlike CRP levels and ESR, serum sTREM-1 levels were not correlated with endoscopic activity in patients with intestinal BD.
PMCID: PMC4075400  PMID: 24954324
C-reactive protein; endoscopic activity; erythrocyte sedimentation rate; intestinal Behçet's disease; triggering receptor expressed on myeloid cells-1
14.  From so simple a beginning 
PMCID: PMC3394996  PMID: 22803006
15.  A tribute to a deceased genius 
PMCID: PMC3349043  PMID: 22586519
16.  Sense & Sensibility 
PMCID: PMC3296929  PMID: 22413067
17.  Fabrication of flexible, multimodal light-emitting devices for wireless optogenetics 
Nature protocols  2013;8(12):2413-2428.
The rise of optogenetics provides unique opportunities to advance materials and biomedical engineering as well as fundamental understanding in neuroscience. This protocol describes the fabrication of optoelectronic devices for studying intact neural systems. Unlike optogenetic approaches that rely on rigid fiber optics tethered to external light sources, these novel devices utilize flexible substrates to carry wirelessly powered microscale, inorganic light-emitting diodes (μ-ILEDs) and multimodal sensors inside the brain. We describe the technical procedures for construction of these devices, their corresponding radiofrequency power scavengers, and their implementation in vivo for experimental application. In total, the timeline of the procedure, including device fabrication, implantation, and preparation to begin in vivo experimentation, can be completed in approximately 3–8 weeks. Implementation of these devices allows for chronic (tested up to six months), wireless optogenetic manipulation of neural circuitry in animals experiencing behaviors such as social interaction, home cage, and other complex natural environments.
PMCID: PMC4005292  PMID: 24202555
18.  Comparison of alveolar ridge preservation methods using three-dimensional micro-computed tomographic analysis and two-dimensional histometric evaluation 
Imaging Science in Dentistry  2014;44(2):143-148.
This study evaluated the efficacy of alveolar ridge preservation methods with and without primary wound closure and the relationship between histometric and micro-computed tomographic (CT) data.
Materials and Methods
Porcine hydroxyapatite with polytetrafluoroethylene membrane was implanted into a canine extraction socket. The density of the total mineralized tissue, remaining hydroxyapatite, and new bone was analyzed by histometry and micro-CT. The statistical association between these methods was evaluated.
Histometry and micro-CT showed that the group which underwent alveolar preservation without primary wound closure had significantly higher new bone density than the group with primary wound closure (P<0.05). However, there was no significant association between the data from histometry and micro-CT analysis.
These results suggest that alveolar ridge preservation without primary wound closure enhanced new bone formation more effectively than that with primary wound closure. Further investigation is needed with respect to the comparison of histometry and micro-CT analysis.
PMCID: PMC4061298  PMID: 24944964
Bone Substitutes; Polytetrafluoroethylene; X-Ray, Microtomography
19.  Va, Pensiero 
PMCID: PMC3051050  PMID: 21394290
20.  Efficacy of early immunomodulator therapy on the outcomes of Crohn’s disease 
BMC Gastroenterology  2014;14:85.
The natural course of Crohn’s disease (CD), with continuing relapses and remissions, leads to irreversible intestinal damage. Early adoption of immunomodulator therapy has been proposed in order to address this; however, it is still uncertain whether early immunomodulator therapy could affect the natural course of the disease in real practice. We evaluated the efficacy of such therapy on the prognosis of newly diagnosed patients with CD.
This retrospective study included 168 patients who were newly diagnosed with CD and who started treatment at Severance Hospital, Seoul, Korea between January 2006 and March 2013. The short- and long-term outcomes were compared between patients treated with early immunomodulator therapy and those treated with conventional therapy.
A Kaplan-Meier analysis identified that administration of immunomodulators within 6 months after diagnosis of CD was superior to conventional therapy in terms of clinical remission and corticosteroid-free remission rates (P=0.043 and P=0.035). However, P=0.827). Patients with a baseline elevated CRP level were more likely to relapse (P<0.005). Drug-related adverse events were more frequent in the early immunomodulator therapy group than in the conventional therapy group P=0.029).
Early immunomodulator therapy was more effective than conventional therapy in inducing remission, but not in preventing relapse. Baseline high CRP level was a significant indicator of relapse.
PMCID: PMC4017088  PMID: 24886458
Crohn’s disease; Azathioprine; 6-mercaptopurine; Immunomodulator
21.  Genesis revisited 
PMCID: PMC3021164  PMID: 21246014
22.  Up in the air 
PMCID: PMC2967807  PMID: 21072216
23.  En attendant Godot 
PMCID: PMC2931302  PMID: 20827323
24.  Biological effects of a semiconductor diode laser on human periodontal ligament fibroblasts 
It has been reported that low-level semiconductor diode lasers could enhance the wound healing process. The periodontal ligament is crucial for maintaining the tooth and surrounding tissues in periodontal wound healing. While low-level semiconductor diode lasers have been used in low-level laser therapy, there have been few reports on their effects on periodontal ligament fibroblasts (PDLFs). We performed this study to investigate the biological effects of semiconductor diode lasers on human PDLFs.
Human PDLFs were cultured and irradiated with a gallium-aluminum-arsenate (GaAlAs) semiconductor diode laser of which the wavelength was 810 nm. The power output was fixed at 500 mW in the continuous wave mode with various energy fluencies, which were 1.97, 3.94, and 5.91 J/cm2. A culture of PDLFs without laser irradiation was regarded as a control. Then, cells were additionally incubated in 72 hours for MTS assay and an alkaline phosphatase (ALPase) activity test. At 48 hours post-laser irradiation, western blot analysis was performed to determine extracellular signal-regulated kinase (ERK) activity. ANOVA was used to assess the significance level of the differences among groups (P<0.05).
At all energy fluencies of laser irradiation, PDLFs proliferation gradually increased for 72 hours without any significant differences compared with the control over the entire period taken together. However, an increment of cell proliferation significantly greater than in the control occurred between 24 and 48 hours at laser irradiation settings of 1.97 and 3.94 J/cm2 (P<0.05). The highest ALPase activity was found at 48 and 72 hours post-laser irradiation with 3.94 J/cm2 energy fluency (P<0.05). The phosphorylated ERK level was more prominent at 3.94 J/cm2 energy fluency than in the control.
The present study demonstrated that the GaAlAs semiconductor diode laser promoted proliferation and differentiation of human PDLFs.
PMCID: PMC2895515  PMID: 20607054
Alkaline phosphatase; Extracellular signal-regulated kinases; Fibroblasts; Periodontal ligament; Semiconductor diode lasers
25.  Bone regeneration effects of human allogenous bone substitutes: a preliminary study 
The purpose of this study was to compare the bone regeneration effects of cortical, cancellous, and cortico-cancellous human bone substitutes on calvarial defects of rabbits.
Four 8-mm diameter calvarial defects were created in each of nine New Zealand white rabbits. Freeze-dried cortical bone, freeze-dried cortico-cancellous bone, and demineralized bone matrix with freeze-dried cancellous bone were inserted into the defects, while the non-grafted defect was regarded as the control. After 4, 8, and 12 weeks of healing, the experimental animals were euthanized for specimen preparation. Micro-computed tomography (micro-CT) was performed to calculate the percent bone volume. After histological evaluation, histomorphometric analysis was performed to quantify new bone formation.
In micro-CT evaluation, freeze-dried cortico-cancellous human bone showed the highest percent bone volume value among the experimental groups at week 4. At week 8 and week 12, freeze-dried cortical human bone showed the highest percent bone volume value among the experimental groups. In histologic evaluation, at week 4, freeze-dried cortico-cancellous human bone showed more prominent osteoid tissue than any other group. New bone formation was increased in all of the experimental groups at week 8 and 12. Histomorphometric data showed that freeze-dried cortico-cancellous human bone showed a significantly higher new bone formation percentile value than any other experimental group at week 4. At week 8, freeze-dried cortical human bone showed the highest value, of which a significant difference existed between freeze-dried cortical human bone and demineralized bone matrix with freeze-dried cancellous human bone. At week 12, there were no significant differences among the experimental groups.
Freeze-dried cortico-cancellous human bone showed swift new bone formation at the 4-week healing phase, whereas there was less difference in new bone formation among the experimental groups in the following healing phases.
PMCID: PMC2895519  PMID: 20607058
Bone Substitutes; Osteogenesis; Transplantation; X-Ray Microtomography

Results 1-25 (75)