The aim of this study is to fabricate nanophotosensitizers composed of methoxy poly(ethylene glycol) (mPEG), chlorin e6 (Ce6), and phenylboronic acid pinacol ester (PBAP) with diselenide linkages for ...reactive oxygen species (ROS)-sensitive photodynamic therapy (PDT) of cervical cancer cells. To fabricate nanophotosensitizers, Ce6 was conjugated with mPEG via selenocystamine linkage and then remaining carboxylic acid groups of Ce6 was attached to PBAP (mPEGseseCe6PBAP conjugates). Nanophotosensitizers of mPEGseseCe6PBAP conjugates were prepared by dialysis method. In transmission electron microscope (TEM) observation, nanophotosensitizers of mPEGseseCe6PBAP conjugates have spherical shapes and their diameters were less than 150 nm. The average diameter of mPEGseseCe6PBAP nanophotosensitizers was 92.7 ± 9.6 nm in particle size analysis. When H
O
was added to the nanophotosensitizer solution, nanophotosensitizers were sensitively disintegrated according to the H
O
concentration and then changed from monomodal distribution to multimodal distribution in particle size distribution. Furthermore, Ce6 release from nanophotosensitizers also increased according to the H
O
concentration. When H
O
was added to cell culture of HeLa human cervical cancer cells, intracellular Ce6 uptake of nanophotosensitizers were gradually increased according to the H
O
concentration, indicating that nanophotosensitizers showed ROS-sensitive delivery of Ce6 against cancer cells.As well as free Ce6, nanophotosensitizers in the absence of light irradiation have low intrinsic cytotoxicity against RAW264.7 cells and HeLa cells. However, nanophotosensitizers induced cell death dose-dependently under light irradiation. Especially, nanophotosensitizers showed significantly higher ROS generation and phototoxicity against HeLa cells in vitro. When nanophotosensitizers were intravenously administered to animal tumor xenograft model of HeLa cells, tumor tissues revealed stronger fluorescence intensity than other tissues by light irradiation while absence of light irradiation induced relatively lower fluorescence intensity in tumor tissues, indicating that nanophotosensitizers have sensitivity against oxidative stress in tumor tissues. We suggest that nanophotosensitizers of mPEGseseCe6PBAP conjugates are promising vehicle for PDT of cervical cancer cells.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background/Aims: The combinatorial effects of prophylactic methods for postendoscopic retrograde cholangiopancreatography pancreatitis (PEP) in patients with risk factors remain unclear. In this ...network meta-analysis, we compared the efficacy of various prophylactic strategies to decrease the risk of PEP among patients with risk factors. Methods: A systematic review was performed to identify randomized controlled trials from PubMed, Embase, and the Cochrane Library through July 2021. We used frequentist network meta-analysis to compare the rates of PEP among patients who received prophylactic treatments as follows: class A, rectal nonsteroidal anti-inflammatory drugs; class B, prophylactic pancreatic stent; class C, aggressive hydration; or control, no prophylaxis or active control. We selected those studies that included patients with risk factors for PEP. Results: We identified 19 trials, comprising 4,328 participants. Class ABC (odds ratio OR, 0.08; 95% confidence interval CI, 0.03 to 0.24), class AC (OR, 0.10; 95% CI, 0.02 to 0.47), class AB (OR, 0.12; 95% CI, 0.05 to 0.26), class BC (OR, 0.13; 95% CI, 0.04 to 0.41), class A (OR, 0.16; 95% CI, 0.05 to 0.50), and class B (OR, 0.26; 95% CI, 0.14 to 0.46), were associated with a reduced risk of PEP as compared to that of the control. The most effective prophylaxis was ABC (0.87), followed by AC (0.68), AB (0.65), BC (0.56), A (0.49), and B (0.24) according to P-score. Conclusions: The results of this network meta-analysis suggest that the more prophylactic methods are employed, the better the outcomes. It appears that for patients with risk factors, we need to prevent PEP through the use of these well proven combination strategies.
Gastric cancer is the fifth most common cancer worldwide with a poor survival rate. Therefore, it is important to identify predictive and prognostic biomarkers of gastric cancer. Laminin subunit beta ...1 (LAMB1) is involved in attachment, migration, and organization during development, and its elevated expression has been associated with several cancers. However, the role and mechanism of LAMB1 in gastric cancer remains unknown. Here, we determined that LAMB1 is upregulated in gastric cancer tissues and contributes to cell growth and motility. Using a public database, we showed that LAMB1 expression was significantly upregulated in gastric cancer compared to normal tissues. LAMB1 was also found to be associated with poor prognosis in patients with gastric cancer. Overexpression of LAMB1 elevated cell proliferation, invasion, and migration; however, knockdown of LAMB1 decreased these effects in gastric cancer cells. U0126, an extracellular signal-regulated kinase (ERK) inhibitor, regulated the expression of LAMB1 in gastric cancer cells. Additionally, we showed that c-Jun directly binds to the LAMB1 promoter as a transcription factor and regulates its gene expression via the ERK pathway in gastric cancer cells. Therefore, our study indicates that LAMB1 promotes cell growth and motility via the ERK/c-Jun axis and is a potential biomarker and therapeutic target of gastric cancer.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Raw material of gelidioid red algae yielding high-quality agar has been in short supply due to overharvesting, but in situ farming of gelidioids has not been practical due to their slow growth. To ...produce vegetative seedstock of a cosmopolitan species, Pterocladiella capillacea, we investigated the number and length of regenerated branches arising from sectioned fragments during 3 weeks of laboratory culture at 10, 15, 20, and 25°C. All sectioned fragments formed axis-like branches mostly from the upper cut edge and stolon-like branches mostly from the lower cut edge, showing a high capacity of regeneration and intrinsic bipolarity. At 20°C, the number of regenerated branches increased to 2.74 ± 1.29 on the upper cut edge and 4.26 ± 2.66 on the lower cut edge. Our study reveals that the use of fragments bearing regenerated branches as seedstock can be a simple method to initiate fast propagation for mass cultivation in the sea or outdoor tank.
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FFLJ, NUK, ODKLJ, UL, UM, UPUK
Countries differ in their treatment expertise and research results regarding gastric cancer; hence, treatment guidelines are diverse based on evidence and medical situations. A comprehensive and ...comparative review of each country's guidelines is imperative to understand the similarities and differences among countries. We reviewed and compared five gastric cancer treatment guidelines in terms of endoscopic, surgical, perioperative, and palliative systemic treatment based on evidence levels and recommendation grades, as well as the postoperative follow-up strategies for each guideline. The Korean, Chinese, and European guidelines provided evidence and grading of the recommendations. The United States guidelines suggested categories for evidence and consensus. The Japanese guidelines suggested evidence and recommendations only for systemic treatment. The Korean and Japanese guidelines described endoscopic treatment, surgery, and lymphadenectomy in detail. The Chinese, United States, and European guidelines more intensively considered perioperative chemotherapy. In particular, the indications for chemotherapy and the regimens recommended by each guideline differed slightly. Considering their medical situations, each guideline had some diversity in terms of adopting evidence, which resulted in heterogeneous recommendations. This review will help medical personnel to comprehensively understand the diversity in gastric cancer treatment guidelines for each country in terms of evidence and recommendations.
Background
The Korea National Cancer Screening Program (KNCSP) offers upper endoscopy or upper gastrointestinal series (UGIS) biannually for people aged ≥ 40 years. This study aimed to assess the ...effect of negative screening results on the incidence of and mortality from upper gastrointestinal (GI) cancer.
Methods
A population-based retrospective cohort of 15,850,288 men and women was constructed using data from 3 national databases. The participants were followed until the end of 2017 for data on cancer incidence and in 2019 for data on the vital status. Cox proportional hazard model with time-varying exposure was used to assess the association.
Results
By the end of the follow-up period, 230,783 upper GI cancer cases and 99,348 upper GI cancer deaths were recorded. Negative gastric cancer screening was significantly associated with a lower risk of upper GI cancer in both UGIS (adjusted hazard ratio aHR = 0.81, 95% CI = 0.80–0.82) and upper endoscopy (aHR = 0.67, 95% CI = 0.67–0.68) groups. The HRs for upper GI mortality were 0.55 (95% CI = 0.54–0.56) and 0.21 (95% CI = 0.21–0.22) for the UGIS and upper endoscopy groups, respectively. The most significant reductions in the risk of upper GI cancer (UGIS: aHR = 0.76, 95% CI = 0.74–0.77; upper endoscopy: aHR = 0.60, 95% CI = 0.59–0.61) and death (UGIS: aHR = 0.54, 95% CI = 0.52–0.55; upper endoscopy: aHR = 0.19, 95% CI = 0.19–0.20) were observed among individual aged 60–69 years.
Conclusion
Negative screening cases, especially in upper endoscopy of the KNCSP, were associated with an overall reduction in the risk of and mortality from upper GI cancer.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This randomized, open-label trial aimed to compare the efficacy of 10-day bismuth-containing quadruple therapy (BQT) with 7-day proton-pump inhibitor-clarithromycin containing standard triple therapy ...(STT) as an empirical first-line Helicobacter pylori therapy.
Participants with H. pylori infection were randomly assigned to either 10-day BQT (daily doses of bismuth 300 mg, four times; lansoprazole 30 mg, twice; metronidazole 500 mg, three times; and tetracycline 500 mg, four times) or 7-day STT (lansoprazole 30 mg; amoxicillin 1,000 mg; and clarithromycin 500 mg; each given twice daily). Participants who failed initial therapy were crossed over to the alternative treatment regimen. Primary outcome was the eradication rates of first-line treatment by intention-to-treat analysis.
Study participants (n = 352) were randomized to receive either 10-day BQT (n = 175) or 7-day STT (n = 177). The BQT-group achieved a significantly higher eradication rate than the STT-group in the intention-to-treat analysis (74.3% vs 57.1%, respectively; P = 0.001), modified intention-to-analysis (87.2% 130/149 vs 68.7% 101/147, respectively; P < 0.001) and per-protocol analysis (92.9% 105/113 vs 70.1% 94/134, respectively; P < 0.001). Although there was no serious adverse event, the compliance was lower with BQT than STT as a higher proportion of participants in the BQT-group discontinued therapy because of adverse events than those in the STT-group (23.1% vs 9.1%, respectively; P = 0.001) CONCLUSIONS: Ten-day BQT had higher eradication rates compared to that of the 7-day STT as an empirical first-line treatment for H. pylori eradication in Korea.
ClinicalTrials.gov, NCT02557932. Registered 23 September 2015, https://clinicaltrials.gov/ct2/show/NCT02557932?term=NCT02557932&draw=2&rank=1 .
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The large geographic variations in the incidence of gastric cancer (GC) are likely due to differential environmental exposures, in particular to Helicobacter pylori (H. pylori) infection. We aimed to ...investigate the impact of H. pylori on the epigenome in normal gastric mucosa and methylation changes associated with cancer risk independent of H. pylori. A discovery set of normal gastric mucosa from GC cases (n = 42) and controls (n = 42), nested in a large case–control study and stratified by H. pylori status, were subjected to genome‐wide methylation profiling. Single‐nucleotide polymorphism arrays from peripheral blood leukocytes were used to conduct methylation quantitative trait loci (mQTL) analysis. A validation set of gastric mucosa samples (n = 180) was used in the replication phase. We found 1,924 differentially methylated positions (DMPs) and 438 differentially methylated regions (DMRs) associated with H. pylori infection, most of which were hypermethylated. Significant methylation alterations identified in the initial set were successfully replicated. Furthermore, the H. pylori‐associated DMP/Rs showed marked stability (‘epigenetic memory’) after H. pylori clearance. Interestingly, we found 152 DMRs associated with cancer risk independent of the H. pylori status in normal gastric mucosa. The methylation score derived from three biomarkers was a strong predictor of GC. Finally, the mQTL analysis indicated that the H. pylori‐ and cancer‐specific methylation signatures were minimally affected by genetic variation. The comprehensively characterized methylome changes associated with H. pylori infection and GC risk in our study might serve as potential biomarkers for early cancer progression in tumour‐free gastric mucosa.
What's new?
To investigate why gastric cancer is more prevalent in some countries than others, these authors asked how H. pylori infection affects gene methylation. Here, they compared genomes of normal gastric mucosa from gastric cancer cases and controls, with and without H. pylori infection. They noted changes in methylation correlating with H. pylori infection, including current and prior infections, and identified 438 differently methylated regions associated with H. pylori infections. Interestingly, 152 differently methylated regions correlated with increased gastric cancer risk regardless of H. pylori status. Some of these methylation patterns could lead to biomarkers for detecting disease progression.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background: A positive association between a high iron intake and colorectal cancer has been identified; however, the effect of dietary iron on gastric cancer (GC) remains unclear. Here, we ...investigate whether dietary iron is related to GC risk and whether the transferrin receptor (TFRC) rs9846149 polymorphism modifies this association. Methods: A case–control study was designed to assess this association among 374 GC patients and 754 healthy controls. A self-administered questionnaire was used to collect information on demographics, medical history and lifestyle. Dietary iron intake was assessed using a semi-quantitative food frequency questionnaire. TFRC rs9846149 was genetically analyzed using the Affymetrix Axiom Exom 319 Array platform. Results: A higher total dietary iron was significantly associated with decreased GC risk OR = 0.65 (0.45–0.94), p for trend = 0.018. A similar association was observed with nonheme iron OR = 0.64 (0.44–0.92), p for trend = 0.018. Individuals with a major allele of TFRC rs9846149 (CC/GC) and higher intake of total iron had a significantly lower GC risk than those with a lower intake OR = 0.60 (0.41–0.88), p interaction = 0.035. Conclusion: Our findings show the protective effects of total dietary iron, especially nonheme iron, against GC risk, and this association can be modified by TFRC rs9846149.
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