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  • MDPI AG  (520)
  • 1
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    Metabolic Effects of Gastrectomy and Duodenal Bypass in Early Gastric Cancer Patients with T2DM: A Prospective Single-Center Cohort Study
    MDPI AG ; 2021
    In:  Journal of Clinical Medicine Vol. 10, No. 17 ( 2021-09-04), p. 4008-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 17 ( 2021-09-04), p. 4008-
    Kurzfassung: We evaluated the metabolic effects of gastrectomies and endoscopic submucosal dissections (ESDs) in early gastric cancer (EGC) patients with type 2 diabetes mellitus (T2DM). Forty-one EGC patients with T2DM undergoing gastrectomy or ESD were prospectively evaluated. Metabolic parameters in the patients who underwent gastrectomy with and without a duodenal bypass (groups 1 and 2, n = 24 and n = 5, respectively) were compared with those in patients who underwent ESD (control, n = 12). After 1 year, the proportions of improved/equivocal/worsened glycemic control were 62.5%/29.2%/8.3% in group 1, 40.0%/60.0%/0.0% in group 2, and 16.7%/50.0%/33.3% in the controls, respectively (p = 0.046). The multivariable ordered logistic regression analysis results showed that both groups had better 1-year glycemic control. Groups 1 and 2 showed a significant reduction in postprandial glucose (−97.9 and −67.8 mg/dL), body mass index (−2.1 and −2.3 kg/m2), and glycosylated hemoglobin (group 1 only, −0.5% point) (all p 〈 0.05). Furthermore, improvements in group 1 were more prominent when preoperative leptin levels were high (p for interaction 〈 0.05). Metabolic improvements in both groups were also observed for insulin resistance, leptin, plasminogen activator inhibitor-1, and resistin. Gastrectomy improved glycemic control and various metabolic parameters in EGC patients with T2DM. Patients with high leptin levels may experience greater metabolic benefits from gastrectomy with duodenal bypass.
    Materialart: Online-Ressource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm10174008
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2021
    ZDB Id: 2662592-1
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  • 2
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    Online-Ressource
    Feasibility of Non-Exposure Simple Suturing Endoscopic Full-Thickness Resection in Comparison with Laparoscopic Endoscopic Cooperative Surgery for Gastric Subepithelial Tumors: Results of Two Independent Prospective Trials
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 8 ( 2021-04-13), p. 1858-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 8 ( 2021-04-13), p. 1858-
    Kurzfassung: Recently, nonexposure simple suturing endoscopic full-thickness resection (NESS-EFTR) method was developed to avoid tumor exposure to the peritoneal cavity. The aim of this study is to compare the short-term outcomes of the NESS-EFTR method with those of laparoscopic and endoscopic cooperative surgery (LECS) for gastric subepithelial tumors (SETs). A prospective single-center trial of LECS for gastric SETs was performed from March 2012 to October 2013 with a separate prospective trial of NESS-EFTR performed from August 2015 to June 2017, enrolling 15 patients each. Among the 30 enrolled patients, 14 who underwent LECS and 11 who underwent NESS-EFTR were finally included in the analysis. The rate of complete resection and successful closure was 100% in both groups. The operating time was longer for NESS-EFTR group than for LECS (110 vs. 189 min; p 〈 0.0001). There were no postoperative complications except one case of transient fever in the NESS-EFTR group. One patient in the LECS group had peritoneal seeding of gastrointestinal stromal tumor at 17 months postoperatively, and there was no other recurrence. Although NESS-EFTR had long operating and procedure times, it was feasible for patients with gastric SETs requiring a nonexposure technique.
    Materialart: Online-Ressource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13081858
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2021
    ZDB Id: 2527080-1
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  • 3
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    Effectiveness of a Novel Covered Stent without External Thread Fixation for Anastomotic Leakage after Total or Proximal Gastrectomy for Gastric Cancer
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 15 ( 2021-07-23), p. 3720-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 15 ( 2021-07-23), p. 3720-
    Kurzfassung: A thread-fix stent entails long hospitalization and patient discomfort. We aimed to evaluate the efficacy of a novel stent with silicone-covered outer double layers without external fixation (Beta stent) for anastomotic leakage after total or proximal gastrectomy. The outcomes were compared between gastric cancer patients who underwent stent placement using a thread-fix stent between 2014 and 2015 (Thread-Fix Group) and those who received a Beta stent in the succeeding period until October 2018 (Beta Stent Group). The Beta Stent Group (n = 14) had a significantly higher leakage healing rate by the first stent placement (92.9% vs. 53.8%; p = 0.021) and had a shorter hospitalization period (median: 16 days vs. 28 days; p = 0.037) than the Thread-Fix Group (n = 13). Further, 50% of the Beta stent patients received outpatient management until stent removal. Stent maintenance duration was significantly longer in the Beta Stent Group (median, 28 days vs. 18 days; p = 0.006). There was no significant between-group difference in stent-related complications except for stent migration (7.1% (Beta Stent Group) vs. 0% (Thread-Fix Group), p = 0.326). In conclusion, the Niti-S Beta stent is an effective treatment for anastomotic leakage from total or proximal gastrectomy for gastric cancer. Stent maintenance is possible without hospitalization.
    Materialart: Online-Ressource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13153720
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2021
    ZDB Id: 2527080-1
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  • 4
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    Dietary Carotenoids Intake and the Risk of Gastric Cancer: A Case—Control Study in Korea
    MDPI AG ; 2018
    In:  Nutrients Vol. 10, No. 8 ( 2018-08-07), p. 1031-
    Details
    In: Nutrients, MDPI AG, Vol. 10, No. 8 ( 2018-08-07), p. 1031-
    Kurzfassung: Although the incidence of gastric cancer (GC) has declined, it remains the second most common cancer in Korea. As a class of phytochemicals, carotenoids are fat-soluble pigments that are abundant in fruits and vegetables and have health-promoting properties, including cancer prevention effects. This case-control study investigated the effects of total dietary carotenoids, dietary carotenoid subclasses (α-carotene, β-carotene, β-cryptoxanthin, lutein/zeaxanthin, and lycopene), and foods contributing to the dietary intake of each carotenoid on the risk of GC. Four hundred and fifteen cases and 830 controls were recruited from the National Cancer Center Hospital in Korea between March 2011 and December 2014. A significant inverse association between total dietary carotenoids and GC risk was observed among women (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.32–0.99). A higher intake of dietary lycopene was inversely associated with GC risk overall in the subjects (OR 0.60, 95% CI 0.42–0.85, p for trend = 0.012), men (OR 0.60, 95% CI 0.39–0.93), and women (OR 0.54, 95% CI 0.30–0.96, p for trend = 0.039). This significant association between dietary lycopene intake and GC risk was also observed in the subgroups of Helicobacter pylori (H. pylori)-positive subjects and those who had ever smoked. Among the major contributing foods of dietary lycopene, consumption of tomatoes and tomato ketchup was inversely associated with GC risk in the overall subjects, men, and women. Based on our findings, a higher intake of dietary lycopene and contributing foods of lycopene (tomatoes and tomato ketchup) may be inversely associated with the risk of GC.
    Materialart: Online-Ressource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu10081031
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2018
    ZDB Id: 2518386-2
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  • 5
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    STAT3 Stabilizes IKKα Protein through Direct Interaction in Transformed and Cancerous Human Breast Epithelial Cells
    MDPI AG ; 2020
    In:  Cancers Vol. 13, No. 1 ( 2020-12-30), p. 82-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 1 ( 2020-12-30), p. 82-
    Kurzfassung: Signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB (NF-κB) are two representative transcription factors that play a critical role in inflammation-associated tumorigenesis through multi-level cooperation. Unlike other types of tumors, breast carcinomas have shown a significant dependency on the non-classical NF-κB pathway as well as the classical one. The α subunit of the inhibitor of the κB kinase (IKK) complex, IKKα, is involved in both classical and non-classical activation of NF-κB. Although the cross-talk between STAT3 and NF-κB has been suggested in several studies, the interplay between STAT3 and the regulators of NF-κB including IKKα has not been fully clarified yet. In this study, we observed overexpression and co-localization of IKKα and STAT3 in human breast cancer tissues as well as in H-Ras transformed human breast epithelial (H-Ras MCF-10A) and breast cancer (MDA-MB-231) cells. By utilizing small interfering RNA (siRNA) technology, we were able to demonstrate that STAT3 up-regulated IKKα, but not IKKβ or IKKγ, in these cells. This was attributable to direct binding to and subsequent stabilization of IKKα protein by blocking the ubiquitin-proteasome system. Notably, we identified the lysine 44 residue of IKKα as a putative binding site for STAT3. Moreover, siRNA knockdown of IKKα attenuated viability, anchorage-independent growth and migratory capabilities of H-Ras MCF-10A cells. Taken together, these findings propose a novel mechanism responsible for NF-κB activation by STAT3 through stabilization of IKKα, which contributes to breast cancer promotion and progression. Thus, breaking the STAT3-IKKα alliance can be an alternative therapeutic strategy for the treatment of breast cancer.
    Materialart: Online-Ressource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13010082
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2020
    ZDB Id: 2527080-1
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  • 6
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    Alterations in Gastric Microbial Communities Are Associated with Risk of Gastric Cancer in a Korean Population: A Case-Control Study
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 9 ( 2020-09-14), p. 2619-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 9 ( 2020-09-14), p. 2619-
    Kurzfassung: Although the microbiome has a potential role in gastric cancer (GC), little is known about microbial dysbiosis and its functions. This study aimed to observe the associations between the alterations in gastric microbial communities and GC risk. The study participants included 268 GC patients and 288 controls. The 16S rRNA gene sequencing was performed to characterize the microbiome. Streptococcus_NCVM and Prevotella melaninogenica species were highly enriched in cases and controls, respectively. Those who were in the third tertile of P. melaninogenica showed a significantly decreased risk of GC in total (odds ratio (OR): 0.91, 95% confidence interval (CI): 0.38–0.96, p-trend = 0.071). Class Bacilli was phylogenetically enriched in cases, while phylum Actinobacteria, class Actinobacteria were related to the controls. The microbial dysbiosis index (MDI) was significantly higher for the cases compared with the healthy controls in the female population (p = 0.002). Females in the third tertile of the MDI showed a significantly increased risk of GC (OR: 2.66, 95% CI: 1.19-5.99, p-trend = 0.017). Secondary bile acid synthesis and biosynthesis of ansamycins pathways were highly abundant in cases and controls, respectively. Dysbiosis of gastric microbial communities is associated with an increased risk of GC specifically in females.
    Materialart: Online-Ressource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12092619
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2020
    ZDB Id: 2527080-1
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  • 7
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    Phenethyl Isothiocyanate-Conjugated Chitosan Oligosaccharide Nanophotosensitizers for Photodynamic Treatment of Human Cancer Cells
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 22 ( 2022-11-09), p. 13802-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 22 ( 2022-11-09), p. 13802-
    Kurzfassung: The aim of this study is to synthesize phenethyl-conjugated chitosan oligosaccharide (COS) (abbreviated as ChitoPEITC) conjugates and then fabricate chlorin E6 (Ce6)-incorporated nanophotosensitizers for photodynamic therapy (PDT) of HCT-116 colon carcinoma cells. PEITC was conjugated with the amine group of COS. Ce6-incorporated nanophotosensitizers using ChitoPEITC (ChitoPEITC nanophotosensitizers) were fabricated by dialysis method. 1H nuclear magnetic resonance (NMR) spectra showed that specific peaks of COS and PEITC were observed at ChitoPEITC conjugates. Transmission electron microscope (TEM) confirmed that ChitoPEITC nanophotosensitizers have spherical shapes with small hydrodynamic diameters less than 200 nm. The higher PEITC contents in the ChitoPEITC copolymer resulted in a slower release rate of Ce6 from nanophotosensitizers. Furthermore, the higher Ce6 contents resulted in a slower release rate of Ce6. In cell culture study, ChitoPEITC nanophotosensitizers showed low toxicity against normal CCD986Sk human skin fibroblast cells and HCT-116 human colon carcinoma cells in the absence of light irradiation. ChitoPEITC nanophotosensitizers showed a significantly higher Ce6 uptake ratio than that of free Ce6. Under light irradiation, cellular reactive oxygen species (ROS) production of nanophotosensitizers was significantly higher than that of free Ce6. Especially, PEITC and/or ChitoPEITC themselves contributed to the production of cellular ROS regardless of light irradiation. ChitoPEITC nanophotosensitizers showed significantly higher PDT efficacy against HCT-116 cells than that of free Ce6. These results indicate that ChitoPEITC nanophotosensitizers have superior potential in Ce6 uptake, ROS production and PDT efficacy. In the HCT-116 cell-bearing mice tumor-xenograft model, ChitoPEITC nanophotosensitizers efficiently inhibited growth of tumor volume rather than free Ce6. In the animal imaging study, ChitoPEITC nanophotosensitizers were concentrated in the tumor tissue, i.e., fluorescence intensity in the tumor tissue was stronger than that of other tissues. We suggest that ChitoPEITC nanophotosensitizers are a promising candidate for the treatment of human colon cancer cells.
    Materialart: Online-Ressource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms232213802
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2022
    ZDB Id: 2019364-6
    SSG: 12
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  • 8
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    Reactive Oxygen Species-Sensitive Nanophotosensitizers of Methoxy Poly(ethylene glycol)-Chlorin e6/Phenyl Boronic Acid Pinacol Ester Conjugates Having Diselenide Linkages for Photodynamic Therapy of Cervical Cancer Cells
    MDPI AG ; 2021
    In:  Materials Vol. 15, No. 1 ( 2021-12-25), p. 138-
    Details
    In: Materials, MDPI AG, Vol. 15, No. 1 ( 2021-12-25), p. 138-
    Kurzfassung: 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 H2O2 was added to the nanophotosensitizer solution, nanophotosensitizers were sensitively disintegrated according to the H2O2 concentration and then changed from monomodal distribution to multimodal distribution in particle size distribution. Furthermore, Ce6 release from nanophotosensitizers also increased according to the H2O2 concentration. When H2O2 was added to cell culture of HeLa human cervical cancer cells, intracellular Ce6 uptake of nanophotosensitizers were gradually increased according to the H2O2 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.
    Materialart: Online-Ressource
    ISSN: 1996-1944
    URL: Article
    DOI: 10.3390/ma15010138
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2021
    ZDB Id: 2487261-1
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  • 9
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    Structural and Biophysical Analyses of Human N-Myc Downstream-Regulated Gene 3 (NDRG3) Protein
    MDPI AG ; 2020
    In:  Biomolecules Vol. 10, No. 1 ( 2020-01-06), p. 90-
    Details
    In: Biomolecules, MDPI AG, Vol. 10, No. 1 ( 2020-01-06), p. 90-
    Kurzfassung: The N-Myc downstream-regulated gene (NDRG) family belongs to the α/β-hydrolase fold and is known to exert various physiologic functions in cell proliferation, differentiation, and hypoxia-induced cancer metabolism. In particular, NDRG3 is closely related to proliferation and migration of prostate cancer cells, and recent studies reported its implication in lactate-triggered hypoxia responses or tumorigenesis. However, the underlying mechanism for the functions of NDRG3 remains unclear. Here, we report the crystal structure of human NDRG3 at 2.2 Å resolution, with six molecules in an asymmetric unit. While NDRG3 adopts the α/β-hydrolase fold, complete substitution of the canonical catalytic triad residues to non-reactive residues and steric hindrance around the pseudo-active site seem to disable the α/β-hydrolase activity. While NDRG3 shares a high similarity to NDRG2 in terms of amino acid sequence and structure, NDRG3 exhibited remarkable structural differences in a flexible loop corresponding to helix α6 of NDRG2 that is responsible for tumor suppression. Thus, this flexible loop region seems to play a distinct role in oncogenic progression induced by NDRG3. Collectively, our studies could provide structural and biophysical insights into the molecular characteristics of NDRG3.
    Materialart: Online-Ressource
    ISSN: 2218-273X
    URL: Article
    DOI: 10.3390/biom10010090
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2020
    ZDB Id: 2701262-1
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  • 10
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    Development of 454 New Kompetitive Allele-Specific PCR (KASP) Markers for Temperate japonica Rice Varieties
    MDPI AG ; 2020
    In:  Plants Vol. 9, No. 11 ( 2020-11-10), p. 1531-
    Details
    In: Plants, MDPI AG, Vol. 9, No. 11 ( 2020-11-10), p. 1531-
    Kurzfassung: Temperate japonica rice varieties exhibit wide variation in the phenotypes of several important agronomic traits, including disease resistance, pre-harvest sprouting resistance, plant architecture, and grain quality, indicating the presence of genes contributing to favorable agronomic traits. However, gene mapping and molecular breeding has been hampered as a result of the low genetic diversity among cultivars and scarcity of polymorphic DNA markers. Single nucleotide polymorphism (SNP)-based kompetitive allele-specific PCR (KASP) markers allow high-throughput genotyping for marker-assisted selection and quantitative trait loci (QTL) mapping within closely related populations. Previously, we identified 740,566 SNPs and developed 771 KASP markers for Korean temperate japonica rice varieties. However, additional markers were needed to provide sufficient genome coverage to support breeding programs. In this study, the 740,566 SNPs were categorized according to their predicted impacts on gene function. The high-impact, moderate-impact, modifier, and low-impact groups contained 703 (0.1%), 20,179 (2.7%), 699,866 (94.5%), and 19,818 (2.7%) SNPs, respectively. A subset of 357 SNPs from the high-impact group was selected for initial KASP marker development, resulting in 283 polymorphic KASP markers. After incorporation of the 283 markers with the 771 existing markers in a physical map, additional markers were developed to fill genomic regions with large gaps between markers, and 171 polymorphic KASP markers were successfully developed from 284 SNPs. Overall, a set of 1225 KASP markers was produced. The markers were evenly distributed across the rice genome, with average marker density of 3.3 KASP markers per Mbp. The 1225 KASP markers will facilitate QTL/gene mapping and marker-assisted selection in temperate japonica rice breeding programs.
    Materialart: Online-Ressource
    ISSN: 2223-7747
    URL: Article
    DOI: 10.3390/plants9111531
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2020
    ZDB Id: 2704341-1
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