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Although gut microbiome dysbiosis has been associated with inflammatory bowel disease (IBD), the relationship between the oral microbiota and IBD remains poorly understood. This study aimed to identify unique microbiome patterns in saliva from IBD patients and explore potential oral microbial markers for differentiating Crohn’s disease (CD) and ulcerative colitis (UC). A prospective cohort study recruited IBD patients (UC: n = 175, CD: n = 127) and healthy controls (HC: n = 100) to analyze their oral microbiota using 16S rRNA gene sequencing. Machine learning models (sparse partial least squares discriminant analysis (sPLS-DA)) were trained with the sequencing data to classify CD and UC. Taxonomic classification resulted in 4041 phylotypes using Kraken2 and the SILVA reference database. After quality filtering, 398 samples (UC: n = 175, CD: n = 124, HC: n = 99) and 2711 phylotypes were included. Alpha diversity analysis revealed significantly reduced richness in the microbiome of IBD patients compared to healthy controls. The sPLS-DA model achieved high accuracy (mean accuracy: 0.908, and AUC: 0.966) in distinguishing IBD vs. HC, as well as good accuracy (0.846) and AUC (0.923) in differentiating CD vs. UC. These findings highlight distinct oral microbiome patterns in IBD and provide insights into potential diagnostic markers.

Background: The treatment of inflammatory bowel diseases has evolved with the development of anti-tumor necrosis factor agents. Despite the long-term effectiveness, many patients experience primary non-response, secondary loss of response, or intolerance. Therefore, the development of new drugs that act on different inflammatory pathways has become necessary. This review focuses on biologic agents and new therapies for the treatment of inflammatory bowel diseases.Current Concepts: Vedolizumab, a gut-selective agent that targets α4β7 integrin is effective in both ulcerative colitis and Crohn’s disease. Ustekinumab is a monoclonal antibody that binds to p40 subunit of interleukin-12/interleukin-23. Ustekinumab is available for the treatment of Crohn’s disease and ulcerative colitis. Tofacitinib is the first Janus kinase inhibitor approved for the treatment of ulcerative colitis. The advantage of tofacitinib is an oral prescription medicine and has rapid action.Discussion and Conclusion: Since vedolizumab, ustekinumab and tofacitinib are effective agents for the treatment of inflammatory bowel diseases, positioning of old and new biologic agents and small molecules should be determined. The safety and efficacy of novel and emerging drugs needs to be evaluated in patients with inflammatory bowel disease.

A large body of research has demonstrated a synergistic anticancer effect between docosahexaenoic acid (DHA) and standard chemotherapy regimens against colorectal cancer (CRC). In this study, we investigated the chemotherapeutic potential of cotreatment with DHA and isoliquiritigenin (ISL) against CRC HCT-116 cells. Apoptosis was confirmed by Annexin V/PI staining and expression of apoptosis-associated proteins. The synergistic effect of DHA and ISL combination on apoptosis was detected using combination index approaches. Flow cytometry was carried out using fluorescent probes to measure the production of reactive oxygen species (ROS). DHA and ISL in combination synergistically enhanced the decrease in cell viability versus the compounds used alone. Moreover, we demonstrated that the synergistic anti-CRC activity of cotreatment with these two compounds was achieved by inducing the apoptosis caspase-dependently mediated through augmented ROS generation followed by increased Fas ligand mRNA expression and cytochrome c release. Our data also demonstrated that cotreating with DHA and ISL strongly upregulated the phosphorylation of ERK and JNK, which are functionally associated with ROS induced by the two compounds in combination. Interestingly, further study revealed that inhibiting ERK phosphorylation strongly enhanced Fas ligand mRNA expression and the combination of the two compounds induced stronger cytotoxicity, whereas inhibiting JNK phosphorylation significantly reduced the apoptotic signals mediated by cotreatment with these two compounds. Excessive ROS-induced JNK activation and cytochrome c release from mitochondria played a key role in the synergistic anticancer activity of CRC cells by cotreating with DHA and ISL.

Background Endoscopic assessment of disease activity is a key parameter in the management of ulcerative colitis. Whether sigmoidoscopy alone is sufficient to evaluate the disease activity in ulcerative colitis lacks studies. Methods We retrospectively analyzed the medical records and endoscopic results of patients with ulcerative colitis followed by colonoscopy in seven tertiary hospitals between January 2012 and December 2018. Endoscopic disease activity was scored using the Mayo endoscopic subscore (MES) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) for each segment from the colonoscopy images. Concordance was evaluated by comparing the highest MES and UCEIS in the rectosigmoid and proximal regions to confirm the usefulness of sigmoidoscopy. Results A total of 500 colonoscopic examinations from 333 patients were enrolled. Only in 7.6% [k(kappa): 0.893, r(Spearman): 0.906, p 0.001] and 8.6% [k(kappa): 0.890, r(Spearman): 0.914; p 0.001] of cases, MES and UCEIS scored more severely in the proximal colon. Comparison of active disease (MES ≥ 2) in the rectosigmoid area and the entire colon showed a high concordance rate [k(kappa): 0.899, r(Spearman): 0.904, p 0.001]. Endoscopic healing (MES = 0) also showed a high concordance rate [k(kappa): 0.882, r(Spearman): 0.887, p 0.001]. In 38 cases (7.6%) of patients with a higher MES in the proximal area, it was significantly higher in patients with previous extensive colitis. Conclusions Sigmoidoscopy and colonoscopy showed a high concordance rate. Therefore, sigmoidoscopy is considered a sufficient substitute for colonoscopy. However, colonoscopy should be considered in patients with previous extensive colitis.

Background/Aims: In ulcerative colitis (UC) patients, Escherichia coli Nissle 1917 (EcN) is equivalent to mesalazine for preventing disease relapse; however, evidence of the ability of EcN to increase health-related quality of life or induce remission remains scarce. We investigated the efficacy of EcN as an add-on therapy for UC.Methods: In this multicentre, double-blind, randomised, placebo-controlled study, a total of 133 UC patients were randomly assigned to receive either EcN or placebo once daily for 8 weeks. Inflammatory bowel disease questionnaire (IBDQ) scores (primary endpoint) and clinical remission and response rates (secondary endpoints) were compared (Clinical trial registration number: NCT04969679).Results: In total, 118 patients (EcN, 58; placebo, 60) completed the study. The number of patients reaching the primary endpoint did not differ between the EcN and placebo groups (30 [51.7%] vs. 31 [51.7%]; per-protocol analysis, p = 1.0; intention-to-treat analysis, p = 0.86). However, significantly fewer patients in the EcN group exhibited a decreased IBDQ score (1 [1.7%] vs. 8 [13.3%]; per-protocol analysis, p = 0.03; intention- to-treat analysis, p = 0.02). Moreover, a significantly higher number of patients in the EcN group displayed clinical response at 4 weeks (23 [39.7%] vs. 13 [21.7%], p = 0.04) and endoscopic remission at 8 weeks (26 [46.4%] vs. 16 [27.1%], p = 0.03).Conclusions: Although the number of patients reaching the primary endpoint did not differ between the EcN and placebo groups, EcN was found to be safe and effective in preventing the exacerbation of IBDQ scores and achieving clinical responses and endoscopic remission in patients with mild-to-moderate UC.

Rectal involvement by systemic lupus erythematosus (SLE) is quite rare. Approximately 14 cases have been reported worldwide, but only one with ischemic colitis has been reported in Korea. A 17-year-old female patient was hospitalized with abdominal pain and hematochezia. Sigmoidoscopy revealed only a simple rectal ulcer without ischemic colitis. cytomegalovirus and bacterial infections were excluded. A sigmoidoscopic rectal biopsy indicated a rectal invasion by SLE, but the patient showed an acute worsening conditions that did not respond to treatment. This paper reports a case of rectal ulcer that developed in SLE without ischemic colitis with a review of the relevant literature.

The use of 5-ASA, immunomodulators, biologics, and small molecule drugs are the main treatment for inflammatory bowel disease (IBD), however, fecal microbiota transplantation (FMT) is also drawing attention as a treatment to improve intestinal dysbiosis by transplantaing normal human stool into patients with IBD. FMT demonstrates relatively good effects in inducing clinical remission in IBD, but unlike Clostridium difficile infection, multiple FMT can enhance the clinical effect. There are no reports of the long-term effectiveness and safety of FMT conducted in IBD yet, therefore, well-designed, prospective studies will be needed. Gut microbiota can affect inflammatory response, intestinal barrier function, and host metabolism, so microbe-based therapies are likely to be a new treatment option for IBD. The deeper the understanding of microbe products or effectors, the more likely it is to provide personalized therapy in IBD.

Background We investigated the real-life effectiveness and safety of vedolizumab (VDZ) induction therapy among Korean patients with Crohn disease (CD) or ulcerative colitis (UC) for whom anti-tumor necrosis factor therapy previously failed. Methods Adult patients who started VDZ induction therapy at 16 centers were prospectively enrolled in the Korean VDZ nationwide registry. The coprimary outcomes were clinical remission, defined as a Crohn’s Disease Activity Index score Results Between August 2017 and November 2019, a total of 158 patients (80 with CD and 78 with UC) received VDZ induction therapy. Clinical remission rates among patients with CD and patients with UC were 44.1% and 44.0%, respectively. Among patients with UC, the endoscopic remission rate was 32.4%. Clinical response and remission rates showed increasing trends during induction therapy. Multivariable analysis revealed that clinical response at week 6 was the only predictor of clinical remission at week 14 for both patients with CD and patients with UC. Among patients who experienced 1 or more adverse events (n = 71; 44.9%), disease exacerbation (n = 28; 17.7%) was the most common adverse event. Conclusions Among Korean patients with CD or UC for whom anti-tumor necrosis factor therapy failed, VDZ induction therapy was effective and safe. The early clinical response was associated with clinical remission after VDZ induction therapy.

Esophagogastroduodenoscopy for cancer screening was performed in a 55-year-old woman as part of a health screening program, and revealed a depressed lesion approximately 20 mm in diameter in the lesser curvature of the mid-gastric body. Several biopsy specimens were collected as the lesion resembled early gastric cancer; however, histopathologic evaluation revealed chronic active gastritis with an ulcer and amorphous eosinophilic material deposition. Congo red staining identified amyloid proteins, and apple-green birefringence was shown using polarized light microscopy. Immunohistochemical staining revealed the presence of kappa and lambda chain-positive plasma cells. There was no evidence of underlying plasma cell dyscrasia or amyloid deposition in other segments of the gastrointestinal tract. Echocardiography and computed tomography of the chest, abdomen, and pelvis did not show any significant findings. Thus, the patient was diagnosed with localized gastric amyloidosis with kappa and lambda light chain coexpression.

Background We investigated the real-life effectiveness and safety of vedolizumab maintenance treatment among Korean patients with Crohn’s disease (CD) or ulcerative colitis (UC) who previously failed anti-tumour necrosis factor (anti-TNF) therapy. Methods Adult patients with CD or UC who have previously failed anti-TNF therapy and received vedolizumab were prospectively enrolled from 16 hospitals in Korea. The primary outcome was clinical remission at week 54. Clinical remission was defined as a Crohn’s disease activity index (CDAI) Results Between August 2017 to July 2020, a total of 165 patients (81 with CD and 84 with UC) received vedolizumab therapy, of whom 154 patients (93.3%) (75 with CD and 79 with UC) received vedolizumab maintenance therapy (Table 1). Clinical remission and response rates at week 54 were 22.2% and 24.1% among patients with CD and 41.4% and 45.7% among patients with UC, respectively (Figure 1A and 1B). Among 70 patients with UC with baseline Mayo endoscopic subscore ≥2, endoscopic remission (Mayo endoscopic subscore ≤1) at week 54 was observed in 19 patients (27.1%). Out of 50 patients with CD with ulcers in baseline endoscopy, 2 patients (4%) showed a disappearance of ulcers at week 54 (Figure 1C). In the multivariable analysis, age at baseline (adjusted odds ration [aOR] 1.065, 95% confidence interval [CI] 1.003–1.131, P=0.041) and Mayo endoscopic subscore at baseline (aOR 0.141, 95% CI 0.026–0.746, P=0.021) were significantly associated with clinical remission at week 54 among patients with UC (Table 2). No factors were found to be associated with clinical remission at week 54 among patients with CD. Among patients who experienced one or more adverse events (n=134, 81.2%), serious adverse events occurred in 82 patients (49.7%) (Table 3). Disease exacerbation was the most common adverse events (n=89, 53.9%). Conclusion The real-life effectiveness of vedolizumab maintenance treatment for Korean patients with UC who failed anti-TNF therapy was generally similar with the outcomes reported from the previous Western studies. A substantial proportion of patients with CD experienced a loss of response during the first year of treatment. Less severe disease at baseline was associated with clinical remission at 1 year of vedolizumab therapy among patients with UC.

We aimed to evaluate whether obesity was associated with a certain clinicopathologic characteristics of metachronous CRA. This retrospective longitudinal cohort study included 2,904 subjects who had at least one resected CRA at index colonoscopy and who subsequently underwent one or more surveillance colonoscopies within 5 years. Of the 2,904 subjects, 60.9% (n = 1,769) were normal, 35.8% (n = 1,040) were overweight, and 3.3% (n = 95) were obese. Patients with any metachronous CRA were 53.7% (n = 1,559). In multivariate analyses, higher BMI at index colonoscopy was significantly associated with any metachronous CRA (overweight, OR = 1.07; obese, OR = 1.82; p for trend = 0.049). Regarding the multiplicity, the ORs of ≥ 3, ≥ 4 and ≥ 5 metachronous CRAs significantly increased as index BMI increased (p for trend p for trend = 0.016). Higher index BMI was significantly associated with the risk of multiple metachronous CRAs on surveillance colonoscopy within 5 years.

Background and Aim There is controversy about the surveillance interval after colonoscopy when 5–10 adenomas have been found on index colonoscopy. This study aimed to investigate the risk of colorectal neoplasm (CRN) according to the number of adenomas at index colonoscopy. Methods A retrospective, multicenter study was conducted at 10 university hospitals in Korea. We included 1394 patients with ≥ 3 adenomas at index colonoscopy. The risk of advanced CRN was compared according to the number of adenomas (intermediate risk group, 3–4 small adenomas or at least one ≥ 10 mm, and high risk group, ≥ 5 small adenomas or ≥ 3 at least one ≥ 10 mm). Results Overall, 164 (11.8%) developed an advanced CRN after a mean of 4.0 years from baseline colonoscopy. The 3-year and 5-year risk of advanced CRN was 2.1% (95% CI 2.09–2.11) and 14.4% (95% CI 14.36–14.44) in intermediate risk group and 3.2% (95% CI 3.19–3.21) and 23.3% (95% CI 19.15–19.25) in high risk group (P = 0.01). Having ≥ 5 adenomas (OR = 1.57, 95% CI 1.11–2.23, P = 0.01) detected at index colonoscopy was a significant risk factor for developing advanced CRN. Conclusions Although risk of advanced CRN in patients with 5–10 adenomas was significantly higher than that in patients with 3–4 adenomas, the cumulative risk at 3 years was low at 3.2%. Thus, we suggest that a 3-year surveillance interval might be appropriate for the patients with 5–10 adenomas, and further prospective studies are needed to investigate whether more intensive surveillance is needed in this group.

Background/aims Colorectal laterally spreading tumors (LSTs) are large and superficial neoplasms. Most are adenomatous lesions. Endoscopic mucosal resection (EMR) is a standard technique of removing precursor colorectal lesions. The aim of the present study was to assess the factors associated with the clinical outcomes of EMR for LSTs. Materials and methods A total of 275 patients with LSTs who underwent EMR were enrolled in the study. The clinical outcomes of the patients were analyzed by retrospectively reviewing their medical records. Results The en bloc resection and R0 resection rates were 86.9% and 80.4%, respectively. The bleeding and perforation rates were 7.6% and 0.4%, respectively. The frequency of high-grade dysplasia and adenocarcinoma histology was significantly higher, and the procedure time was significantly longer in LSTs >20 mm than in those ≤20 mm. The R0 resection rate was significantly higher in LSTs ≤20 mm than in those >20 mm. The frequency of piecemeal resection was significantly higher in LSTs with an adenomatous and cancerous pit pattern than in those with a non-neoplastic pit pattern. The frequency of piecemeal resection was significantly higher in LSTs with adenocarcinoma than in those with low-grade dysplasia. Multivariate analysis revealed that adenomatous pit pattern, high-grade dysplasia, or adenocarcinoma was a significant independent risk factor of LSTs for piecemeal resection after EMR. Conclusion EMR is useful for treating ≤20 mm LSTs with regard to curative resection and procedure time. LSTs with an adenomatous pit pattern, high-grade dysplasia, or adenocarcinoma are significant independent risk factors for piecemeal resection after EMR.

The prevalence of lower gastrointestinal bleeding appears to be increasing because of the increase in elderly people.

Background Vedolizumab (VDZ) inhibits gut lymphocyte trafficking by binding to α4β7 integrin, which can be effective for patients with Crohn’s disease (CD) or ulcerative colitis (UC). We aimed to investigate the clinical outcomes and response predictors of VDZ treatment for Korean patients with CD or UC, who were previously failed to anti-tumour necrosis factor (TNF) therapy. Methods Between August 2017 and November 2019, a total of 159 patients with CD (n = 81) or UC (n = 78) received a VDZ induction therapy from 16 centres and were prospectively enrolled. Of those, patients who were evaluated at week 14 after three induction doses of VDZ (week 0, 2, and 6) were analysed. The co-primary endpoints were corticosteroid-free clinical remission and endoscopic remission/response (for UC) at week 14. We also analysed predictors of corticosteroid-free clinical remission, persistence of vedolizumab and safety. Results A total of 153 patients were analysed (CD, 77 [50.3%]; male, 94 [61.4%]; median age, 40 years [range, 17–80]; median disease duration, 8.0 years [range, 0.1–38.0]). All patients had previously experienced failures to at least one anti-TNF agent (one, 105 [68.6%]; two, 44 [28.8%]; three, 4 [2.6%]). Corticosteroid-free clinical remission/response rates in CD and UC patients were 44.6%/51.8% and 39.4%/62.0%, respectively. In patients with UC, endoscopic remission and response rates defined by Mayo endoscopic subscore/ulcerative colitis endoscopic index of severity were 33.8%/14.1% and 55.4%/39.1%, respectively. Multivariate analysis revealed that a clinical response at week 6 were associated with a corticosteroid-free clinical remission at week 14 in both CD (Odds ratio [OR] 33.84, 95% confidence interval [CI] 6.25–183.31, p < 0.001) and UC (OR 12.22, 95% CI 1.30–115.28, p = 0.029). In addition, UC patients with higher baseline levels of C-reactive protein (CRP) and faecal calprotectin were less likely to be in corticosteroid-free clinical remission (CRP > 0.31 mg/dl: OR 0.05, 95% CI 0.00–0.60, p = 0.019; faecal calprotectin > 2,000 μg/g: OR 0.04, 95% CI 0.00–0.93, p = 0.045). The cumulative probabilities of continuing VDZ after one year were 48.7% for CD and 65.7% for UC, respectively. During median 10 months of follow-up periods (range, 3–26 months), disease exacerbation was the most common adverse event (n = 73, 47.7%), followed by nasopharyngitis (n = 23, 15.0%) and arthralgia (n = 19, 12.4%). Conclusion In anti-TNF-failed Korean patients with CD and UC, VDZ induction therapy was effective with an acceptable safety profile. Early clinical response and higher inflammatory burden at baseline were associated with corticosteroid-free clinical remission after VDZ induction therapy.

Inflammatory bowel disease (IBD) is chronic inflammation of the gastrointestinal tract caused by high levels of pro-inflammatory cytokines and epithelial barrier dysfunction. Alnus japonica Steud. (Betulaceae) has been used in traditional Asian medicine. However, the potential of A. japonica for the treatment of intestinal inflammation has not been investigated. This study investigated the effects of ethanol extract from A. japonica bark (AJE) on colonic mucosa injury in mice with dextran sodium sulfate (DSS)-induced colitis. Treatment with AJE ameliorated pathological damage and the histopathologic features of DSS-induced colitis. The administration of AJE also inhibits DSS-induced pro-inflammatory cytokines expression, including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and cyclooxygenase (COX)-2. Notably, AJE administration attenuated the reduction of tight junction proteins, zonula occludens (ZO)-1 and occludin, in DSS-induced colitis. In addition, AJE increased heme oxygenase (HO)-1 expression and prevented DSS-induced apoptosis in colonic epithelial cells. Furthermore, in vitro studies demonstrated that AJE inhibits TNF-α-induced IL-8, IL-1β, and COX-2 expression in human intestinal epithelial HT-29 cells and tert-butyl hydroperoxide-induced reduction of ZO-1 and occludin expression in human intestinal epithelial Caco-2 cells. AJE-induced HO-1 protein expression was also found in both HT-29 and Caco-2 cells. Taken together, our findings demonstrated that AJE inhibits intestinal inflammation and protects against intestinal barrier disruption in mice with DSS-induced colitis in vivo and human intestinal epithelial cells in vitro. These results suggest that AJE might have beneficial effects for the treatment of IBD.

Background/Aims: Endoscopic submucosal dissection (ESD) is an advanced technique that can be used to treat precancer ous and early colorectal neoplasms by facilitating en bloc resection regardless of tumor size. In our study, we investigated the clinicopathological feature and the treatment outcome of patients with colorectal laterally spreading tumors (LSTs) that were treated by ESD. Methods: The study enrolled all of 210 patients with colorectal LSTs who underwent ESD. Clinical outcomes were analyzed by retrospectively reviewing medical records. Results: A cancerous pit pattern (Vi/Vn) was more common in pseudo-depressed (PD) subtype than in flat elevated (FE) subtype. The incidence of adenocarcinoma in the PD subtype and nodular mixed (NM) subtypes was significantly higher than in the homogenous (HG) subtype and FE subtype. The en bloc and R0 resection rates were 89.0% and 85.7%, respectively. The bleeding and perforation rates were 5.2% and 1.9%, respectively. The mean procedure time was much longer in the PD subtype than in the FE subtype. The en bloc resection rate was significantly higher in the NM subtype than in the HG subtype. However, there were no statistically significant differences in mean proce dure time, en bloc resection rate, R0 resection rate, bleeding rate, or perforation rate between LST-granular and LST-nongranu lar types. Conclusions: These results indicate that ESD is acceptable for treating colorectal LSTs concerning en bloc resection, curative resection, and risk of complications. Careful consideration is required for complete resection of the PD subtype and NM subtype because of their higher malignant potential. (Intest Res 2019;17:127-134)

Background/Aims: A once-daily (OD) regimen of 5-aminosalicylic acid (5-ASA) was easier to comply with than a divided daily (DD) regimen, and that treatment efficacy for ulcerative colitis (UC) was not affected by the dosing regimen. This study evalu ated treatment adherence of OD and DD dosing in the Korean UC patients. Methods: This study was a prospective, multicenter, randomized trial. UC patients were enrolled who have been in remission for more than 3 months. Patients were randomly assigned to the OD or DD group in a 1:1 ratio. The primary endpoint was adherence rate measured by tablet counts and self-reported adherence rate at 3, 6, 9, and 12 months. The relapse rate was measured at 1 year. Results: Data from the 180 patients who were randomized were analyzed. Both self-reported adherence rate and adherence rate measured by tablet counts were not different at every points, including 1 year. The patients’ satisfaction of the OD group was higher than that of the DD group (P

Chalcone (1,3-diphenyl-2-propen-1-one) derivatives exert anti-cancer activity by targeting key molecules that can lead to carcinogenesis. We synthesized the chalcone derivative 3-phenyl-1-(2,4,6-tris(methoxymethoxy)phenyl)prop-2-yn-1-one (KB-34) and previously reported its anti-inflammatory activity in macrophages. In this study, we examined the anti-metastatic activity of KB-34 against human colorectal cancer (CRC) cells and elucidated its underlying molecular mechanisms. KB-34 treatment significantly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced migration, as well as the invasion and proliferation of CRC cells (HT-29 and SW620). TPA-induced activation of NF-κB was also markedly suppressed by KB-34 in HT-29 cells. KB-34 suppressed the expression of matrix metalloproteinase-7 (MMP-7) at both the mRNA and protein levels in TPA-stimulated CRC cells (HT-29 and SW620). We also demonstrated that induced heme oxygenase-1 (HO-1) expression in CRC cells (HT-29 and SW620) and HO-1 is required for KB-34-mediated suppression of the expression of MMP-7 in TPA-stimulated HT-29 cells. Additionally, the cyclin-dependent kinase inhibitor p21 was significantly induced by treatment with KB-34 in CRC cells (HT-29 and SW620). Knockdown of HO-1 prevented the induction of p21 expression by KB-34 in HT-29 cells. Furthermore, we also demonstrated that 5-fluorouracil (5-FU) together with KB-34 produced a significantly greater inhibition of growth and stimulation of apoptosis of HT-29 cells than did 5-FU alone. In conclusion, KB-34 inhibits the TPA-stimulated metastatic potential of HT-29 cells by induction of HO-1 and may be a promising anti-cancer agent in chemotherapeutic strategies for CRC.

Isoliquiritigenin (ISL) is a natural flavonoid that exhibits anticancer properties in various carcinoma cell types. However, the precise mechanism responsible for its anticancer activity has not been elucidated fully. In the present study, we examined ISL-mediated apoptotic mechanisms in colorectal cancer (CRC) cells. ISL induced apoptosis in human HCT-116 cells and caused marked induction of p62/SQSTM1 mRNA and protein expression. Similarly, ISL potently inhibited in vivo tumor growth and induced p62/SQSTM1 expression in xenograft tumor tissues. In a p62/SQSTM1 siRNA transfection study, ISL-induced p62/SQSTM1 expression attenuated ISL-mediated apoptosis by reducing caspase-8 activation. ISL potentiated the apoptotic effects of 5-fluorouracil (5-FU) on HCT-116 cells. However, ISL-induced p62/SQSTM1 expression also attenuated the potency of apoptosis induced by the combination of 5-FU and ISL. Our results demonstrate that ISL-induced p62/SQSTM1 upregulation affects ISL-mediated apoptotic potential through attenuation of caspase-8 activation in CRC cells. These findings broaden the understanding of the molecular basis of ISL-mediated apoptosis.

Data regarding outcomes for patients with multiple findings for high-risk adenomas are scarce. To compare the risk for colorectal neoplasm (CRN) recurrence according to the number of high-risk findings. This was a retrospective and multicenter study. Patients who had one or more high-risk adenomas at the index colonoscopy and underwent follow-up colonoscopy 2.5 or more years after the index colonoscopy were included. The number of high-risk findings was defined as follows: number of adenomas larger than 1 cm + number of adenomas with HGD + number of adenomas with a villous component + existence (counted as 1) or nonexistence (counted as 0) of three or more adenomas. A total of 1646 patients were included, and the mean duration between index and follow-up colonoscopy was approximately 4 years. The cumulative incidence rate of recurrent advanced CRN in patients with three or more high-risk findings was higher than that in patients with one or two high-risk findings (p

Background and Aim: Advanced adenoma (> 10 mm in diameter, villous structure, or high-grade dysplasia) in young patients may have different characteristics and prognosis compared with those in older patients. We aimed to compare the incidence of colorectal neoplasms in young patients with older patients after removing high-risk adenoma (advance adenoma or ≥ 3 adenomas). Methods: A retrospective, multicenter study was conducted at 13 university hospitals in Korea. The 1479 patients who removed high-risk adenoma at index colonoscopy and followed by surveillance colonoscopy ≥ 2.5 years after were included. The cumulative incidence of overall and advanced colorectal neoplasms was compared according to the age groups (group 1

This study was supported by a grant (2013-E63004-00) from the Research of Korea Centers for Disease Control and Prevention.

Background and aims Oregonin, a major diarylheptanoid derivative isolated from Alnus japonica , exerts anti-inflammatory effects; however, little is known about the effect of oregonin in intestinal inflammation. The current study investigated the potential of oregonin for clinical applications in the treatment of inflammatory bowel disease (IBD) and elucidated its underlying molecular mechanisms. Methods The anti-inflammatory effect of oregonin in tumor necrosis factor-α (TNF-α)-stimulated human intestinal epithelial HT-29 cells was investigated. In addition, the protective effect of oregonin was determined against disruption of the intestinal barrier in tert -butyl hydroperoxide ( t -BH)-stimulated human intestinal epithelial Caco-2 cells. Results Oregonin suppressed the expression of cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1), IL-8, and IL-1β, and inhibited activation of nuclear factor κB (NF-κB) in HT-29 cells stimulated with TNF-α. Oregonin increased heme oxygenase-1 (HO-1) expression through the ERK1/2 and JNK-dependent signaling pathway, which contributed to the oregonin-mediated suppression of COX-2 expression in the HT-29 cells stimulated with TNF-α. Moreover, oregonin induced AMP-activated protein kinase (AMPK) activation. Knockdown of AMPK abolished the induction of HO-1 protein by oregonin and suppression of oregonin-mediated ICAM-1 and COX-2 expression in the HT-29 cells stimulated with TNF-α. Oregonin prevented the t -BH-induced increase in monolayer permeability through inhibition of the reduction in expression of zonula occludens-1 and occludin in Caco-2 cells. Targeting HO-1 by siRNA transfection attenuated the oregonin-mediated prevention of loss of tight junction proteins and increase in permeability. Conclusion The findings of this study suggest that oregonin is a potential candidate for treatment of IBD by preventing mucosal inflammation and barrier disruption.

Colorectal laterally spreading tumors (LSTs) are large, flat neoplasms that are usually treated using different endoscopic techniques based on their morphology, size, and histology. The aim of this study was to evaluate the clinical outcomes of LSTs with advanced histology treated by endoscopic resection. A total of 246 LSTs with advanced histology [i.e., high-grade dysplasia (HGD) and adenocarcinoma (AC)] treated by endoscopic resection [i.e., endoscopic mucosal resection (EMR), EMR-precutting (EMR-P), and endoscopic submucosal dissection (ESD)] were enrolled. Clinicopathological characteristics were collected by review of patient’s medical records. The en bloc resection and R0 resection rates were 75.6% and 85.0%, respectively. The bleeding and perforation rates were 10.2% and 2.4%, respectively. The frequency of cancerous pit pattern and bleeding was significantly higher in LSTs with AC than in LSTs with HGD. The R0 resection rate in LSTs with HGD was significantly higher than that in LSTs with AC. The frequency of cancerous pit patterns in LST cases with submucosal AC was significantly higher than those with intramucosal AC. The mean size of the LSTs was significantly larger in ESD group than in EMR or EMR-P groups. The frequencies of nodular mixed subtype, cancerous pit patterns, and en bloc resection rates were significantly higher in the ESD group than in the EMR or EMR-P groups. However, the frequency of perforation was significantly higher in EMR-P group than in EMR or ESD groups. These results indicate that ESD is a more acceptable treatment approach for resection of colorectal LSTs of larger size, with nodular mixed subtype, having a cancerous pit pattern or AC, using either en bloc or curative resection methods, compared to EMR or EMR-P procedures.