Background: It is unclear whether long-term use of proton pump inhibitors (PPIs) has a potential carcinogenic effect on the colorectum. Methods: We reviewed a consecutive series of neurosurgery outpatients who underwent two or more colonoscopies between January 2014 and April 2023. Patients in whom the timing of endoscopy was not in accordance with the guidelines and those without a history of previous endoscopy were excluded. In the second colonoscopy, the risk of adenomatous colon polyps was evaluated depending on whether the patient had taken a PPI. Results: In total, 520 patients were enrolled. In the multivariate analysis related to the risk of adenomatous colon polyps, age and aspirin use for >5 years were identified as significant factors. After excluding patients who had taken aspirin for >5 years, the patients were divided into three groups: those who had taken PPIs for >12 months, those who had taken PPIs for >3 months but <12 months, and those who had not taken PPIs. The risk of adenomatous colon polyps in these groups was 35.2%, 32.8%, and 22.8%, respectively (p=0.10). In the post-hoc analysis, there was a significant difference between patients who took PPIs and those who did not (p=0.03). In the multivariate analysis, a history of PPI use for >12 months was a significant risk factor for the development of advanced colon polyps (p=0.03). Conclusion Prolonged PPI use appears to increase the risk of developing adenomatous and advanced colon polyps.

Background: It is unclear whether long-term use of proton pump inhibitors (PPIs) has a potential carcinogenic effect on the colorectum. Methods: We reviewed a consecutive series of neurosurgery outpatients who underwent two or more colonoscopies between January 2014 and April 2023. Patients in whom the timing of endoscopy was not in accordance with the guidelines and those without a history of previous endoscopy were excluded. In the second colonoscopy, the risk of adenomatous colon polyps was evaluated depending on whether the patient had taken a PPI. Results: In total, 520 patients were enrolled. In the multivariate analysis related to the risk of adenomatous colon polyps, age and aspirin use for >5 years were identified as significant factors. After excluding patients who had taken aspirin for >5 years, the patients were divided into three groups: those who had taken PPIs for >12 months, those who had taken PPIs for >3 months but <12 months, and those who had not taken PPIs. The risk of adenomatous colon polyps in these groups was 35.2%, 32.8%, and 22.8%, respectively (p=0.10). In the post-hoc analysis, there was a significant difference between patients who took PPIs and those who did not (p=0.03). In the multivariate analysis, a history of PPI use for >12 months was a significant risk factor for the development of advanced colon polyps (p=0.03). Conclusion Prolonged PPI use appears to increase the risk of developing adenomatous and advanced colon polyps.

Background: It is unclear whether long-term use of proton pump inhibitors (PPIs) has a potential carcinogenic effect on the colorectum. Methods: We reviewed a consecutive series of neurosurgery outpatients who underwent two or more colonoscopies between January 2014 and April 2023. Patients in whom the timing of endoscopy was not in accordance with the guidelines and those without a history of previous endoscopy were excluded. In the second colonoscopy, the risk of adenomatous colon polyps was evaluated depending on whether the patient had taken a PPI. Results: In total, 520 patients were enrolled. In the multivariate analysis related to the risk of adenomatous colon polyps, age and aspirin use for >5 years were identified as significant factors. After excluding patients who had taken aspirin for >5 years, the patients were divided into three groups: those who had taken PPIs for >12 months, those who had taken PPIs for >3 months but <12 months, and those who had not taken PPIs. The risk of adenomatous colon polyps in these groups was 35.2%, 32.8%, and 22.8%, respectively (p=0.10). In the post-hoc analysis, there was a significant difference between patients who took PPIs and those who did not (p=0.03). In the multivariate analysis, a history of PPI use for >12 months was a significant risk factor for the development of advanced colon polyps (p=0.03). Conclusion Prolonged PPI use appears to increase the risk of developing adenomatous and advanced colon polyps.

Background: It is unclear whether long-term use of proton pump inhibitors (PPIs) has a potential carcinogenic effect on the colorectum. Methods: We reviewed a consecutive series of neurosurgery outpatients who underwent two or more colonoscopies between January 2014 and April 2023. Patients in whom the timing of endoscopy was not in accordance with the guidelines and those without a history of previous endoscopy were excluded. In the second colonoscopy, the risk of adenomatous colon polyps was evaluated depending on whether the patient had taken a PPI. Results: In total, 520 patients were enrolled. In the multivariate analysis related to the risk of adenomatous colon polyps, age and aspirin use for >5 years were identified as significant factors. After excluding patients who had taken aspirin for >5 years, the patients were divided into three groups: those who had taken PPIs for >12 months, those who had taken PPIs for >3 months but <12 months, and those who had not taken PPIs. The risk of adenomatous colon polyps in these groups was 35.2%, 32.8%, and 22.8%, respectively (p=0.10). In the post-hoc analysis, there was a significant difference between patients who took PPIs and those who did not (p=0.03). In the multivariate analysis, a history of PPI use for >12 months was a significant risk factor for the development of advanced colon polyps (p=0.03). Conclusion Prolonged PPI use appears to increase the risk of developing adenomatous and advanced colon polyps.

Background/Aims: The effects of probiotic supplementation on Helicobacter pylori (H. pylori) eradication therapy are not completely understood. In this study, we investigated the effects of continuous probiotic administration on eradication rates, recrudescence, and symptom response following completion of a course of H. pylori therapy. Methods: This prospective, randomized, double-blind placebo-controlled trial was performed between June 2018 and 2020. Twohundred seventy patients who received a standard triple regimen for H. pylori eradication, were included in the study. Participants were randomized to receive a probiotic as adjunctive therapy (Enterococcus faecium 4.5×108 and Bacillus subtilis 5.0×107; Medilac-S®, Hanmi Pharmaceuticals, Seoul, Korea) or a placebo (one tablet thrice daily) for 28 days, following H. pylori eradication. Participants who showed successful eradication underwent a repeat 13C-urea breath test after 6 months. Results: Eradication rates in the probiotic and placebo groups were 77.1% and 72.4%, respectively (P=0.48) using per-protocol analysis. Using intention-to-treat analysis, eradication rates were 67.4% and 65.9%, respectively (P=0.43). Of 149 patients who were followed-up after 6 months, four patients had recrudescence (2.7%). Recrudescence rates did not differ between the probiotic and placebo groups. Of the 76 patients who had non-ulcer dyspepsia, 60 (78.9%) showed symptom resolution after 6 months. This beneficial effect was most pronounced in patients with postprandial distress syndrome (P=0.02). Conclusions Consecutive probiotic supplementation following H. pylori eradication therapy did not increase eradication rates or decrease recrudescence rates.

Temozolomide(TMZ)is an anticancer agent used to treat glioblastoma,typically following radiation therapy and/or surgical resection.However,despite its effectiveness,at least 50％of patients do not respond to TMZ,which is associated with repair and/or tolerance of TMZ-induced DNA lesions.Studies have demonstrated that alkyladenine DNA glycosylase(AAG),an enzyme that triggers the base excision repair(BER)pathway by excising TMZ-induced N3-methyladenine(3meA)and N7-methylguanine le-sions,is overexpressed in glioblastoma tissues compared to normal tissues.Therefore,it is essential to develop a rapid and efficient screening method for AAG inhibitors to overcome TMZ resistance in glio-blastomas.Herein,we report a robust time-resolved photoluminescence platform for identifying AAG inhibitors with improved sensitivity compared to conventional steady-state spectroscopic methods.As a proof-of-concept,this assay was used to screen 1440 food and drug administration-approved drugs against AAG,resulting in the repurposing of sunitinib as a potential AAG inhibitor.Sunitinib restored glioblastoma(GBM)cancer cell sensitivity to TMZ,inhibited GBM cell proliferation and stem cell char-acteristics,and induced GBM cell cycle arrest.Overall,this strategy offers a new method for the rapid identification of small-molecule inhibitors of BER enzyme activities that can prevent false negatives due to a fluorescent background.

Chronic inflammation due to a Helicobacter pylori (H. pylori) infection is a representative cause of gastric cancer that can promote gastric carcinogenesis by abnormally activating immune cells and increasing the inflammatory cytokines levels. H. pylori infections directly cause DNA double-strand breaks in gastric epithelial cells and genetic damage by increasing the enzymatic activity of cytidine deaminase. Eventually, gastric cancer is induced through dysplasia. Hypermethylation of tumor suppressor genes is an important cause of gastric cancer because of a H. pylori infection. In addition, the changes in gastric microbiota and the mucosal inflammatory changes associated with a co-infection with the Epstein-Barr virus are associated with gastric cancer development. DNA damage induced by H. pylori and the subsequent responses of gastric stem cells have implications for gastric carcinogenesis. Although the pathogenesis of H. pylori has been established, many uncertainties remain, requiring more study.

Background/Aims: Compared with other regimens, concomitant therapy (CT) used as a first-line regimen for Helicobacter pylori (H. pylori) infection is associated with higher eradication rates. We compared the efficacy of tailored therapy (TT) using bismuth added to standard triple therapy (STT) with CT. Methods: This consecutive study performed between September 2020 and 2021 included 210 patients with H. pylori infection. Two participating gastroenterologists prescribed TT and CT. Multiplex PCR assays were performed before eradication therapy to identify the relevant point mutations and confirm clarithromycin resistance in the TT group (n=105). Patients who showed negative PCR results received 14-day STT and those with positive PCR results received a 14-day regimen of bismuth added to STT. The other group (n=105) received 10-day CT. Results: Based on per-protocol analysis, eradication rates in the TT and CT groups were 89.2% (91/102) and 81.6% (84/103), respectively. We observed no statistically significant intergroup differences in eradication rates (P=0.12). The frequency of estimated clarithromycin resistance confirmed using multiplex PCR assays was 32.4% (34/105), and the eradication rate associated with bismuth add-on STT was 76.5% (26/34) in patients with clarithromycin resistance. Conclusions Considering the current and emerging trends in antibiotic resistance, a therapeutic strategy using TT (bismuth add-on STT) is recommended to minimize unnecessary administration of antibiotics.

Cyclin-dependent kinase 9 (CDK9) activity is correlated with worse outcomes of triple-negative breast cancer (TNBC) patients. The heterodimer between CDK9 with cyclin T1 is essential for maintaining the active state of the kinase and targeting this protein-protein interaction (PPI) may offer promising avenues for selective CDK9 inhibition. Herein, we designed and generated a library of metal complexes bearing the 7-chloro-2-phenylquinoline CˆN ligand and tested their activity against the CDK9-cyclin T1 PPI. Complex 1 bound to CDK9 via an enthalpically-driven binding mode, leading to disruption of the CDK9-cyclin T1 interaction in vitro and in cellulo. Importantly, complex 1 showed promising anti-metastatic activity against TNBC allografts in mice and was comparably active compared to cisplatin. To our knowledge, 1 is the first CDK9-cyclin T1 PPI inhibitor with anti-metastatic activity against TNBC. Complex 1 could serve as a new platform for the future design of more efficacious kinase inhibitors against cancer, including TNBC.