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1
Leocata, Pietro, Pietro Gallo, Alessandro Chiominto, Solidea Saltarelli, Rachele Cioccocioppo, Patrizia Saltarelli, Carlo Di Giacomo, and Luca Ventura. "Is Early Gastric Cancer, Diffuse Type, a Forerunner of Advanced Gastric Cancer?" Tumori Journal 79, no. 2 (April 1993): 108–11. http://dx.doi.org/10.1177/030089169307900205.
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Aims and Background Gastric cancer (GC) represents one of the most Important causes of death by malignancy world wilde. Our retrospective study was carried out on surgical stomach specimens obtained from a series of 552 consecutive cases of GC observed in the Departments of Surgical Pathology of the Public Hospitals of L'Aquila and Atri which cover the 17 % of the entire population of the Italian Region Abruzzo. The aim of the study was to compare the anatomo-clinical characteristics of early GC (EGC) and advanced GC (AGC). Methods The diagnosis was achieved by the criteria of the Lauren's histopathological classification (intestinal and diffuse types). Our study also stratified the cases by sex, age, lymph node metastases and associated lesions such as chronic atrophic gastritis, intestinal metaplasia and dysplasia. Results On an average, patients affected by EGC were 8.1 years younger than those with AGC. This age gap could support the hypothesis that early lesions represent the first stage of AGC. However, when patients were subdivided according to Lauren's classification, the mean age of patients with EGC, diffuse type, was 12.2 years less than that of AGC patients of the corresponding histological type. Furthermore, the subset of patients with EGC, diffuse type, and lymph node metastases was 17.8 years younger than patients affected by AGC diffuse type, with lymph node metastases. Conclusions The present study offers an original survey on GC in a defined Italian population. As far as the intestinal histotype is concerned, the slight age difference between EGC and AGC suggests that these tumors are different steps of the same process. On the contrary, the age distribution suggests that EGC, diffuse type, has a different biological behaviour.
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Ieni, A., V. Barresi, L. Rigoli, R. A. Caruso, and G. Tuccari. "HER2 Status in Premalignant, Early, and Advanced Neoplastic Lesions of the Stomach." Disease Markers 2015 (2015): 1–10. http://dx.doi.org/10.1155/2015/234851.
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Objectives. HER2 expression in gastric cancer (GC) has received attention as a potential target for therapy with Trastuzumab. We reviewed the current knowledge on HER2 status in premalignant gastric lesions and in early (EGC) and advanced (AGC) GC to discuss the possible pathogenetic and prognostic roles of HER2 overexpression in GC.Results. HER2 overexpression was documented in gastric low-grade (LG) and high-grade intraepithelial neoplasia (HG-IEN), with higher frequency in gastric type dysplasia. HER2 overexpression was significantly associated with disease recurrence and poor prognosis in EGC representing an independent risk factor for lymph node metastases. HER2 overexpression was more frequent in AGC characterized by high grade, advanced stage, and high Ki-67 labeling index. The discordance in HER2 status was evidenced between primitive GC and synchronous or metachronous metastases.Conclusions. HER2 overexpression in premalignant gastric lesions suggests its potential involvement in the early steps of gastric carcinogenesis. The assessment of HER2 status in EGC may be helpful for the identification of patients who are at low risk for developing nodal metastases. Finally, the possible discordance in HER2 status between primary GC and its synchronous metastases support routine assessment of HER2 both in the primary GC and in its metastatic lesions.
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Kwon, Tae Jin, Tae Jun Kim, Hyuk Lee, Yang Won Min, Byung-Hoon Min, Jun Haeng Lee, and Jae J. Kim. "Statin Use Decreases the Risk of Metachronous Gastric Cancer in Patients without Helicobacter pylori Infection." Cancers 13, no. 5 (March 1, 2021): 1020. http://dx.doi.org/10.3390/cancers13051020.
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Previous studies have shown that statins reduce the risk of gastric cancer; however, their role has not been adequately studied in patients without Helicobacterpylori infection. We aimed to investigate whether statins reduced the risk of metachronous gastric cancer (GC) in H. pylori-negative patients who underwent endoscopic resection for early gastric cancer (EGC). Retrospective data of 2153 patients recruited between January 2007 and December 2016, with no H. pylori infection at baseline, who underwent resection for EGC, were analyzed. Metachronous GC was defined as a newly developed GC at least 1 year after endoscopic resection. Patients who used statins for at least 28 days during the follow-up period were considered as statin users. During a median follow-up of 5 years (interquartile range, 3.5–6.2), metachronous GC developed in 165 (7.6%) patients. In the multivariate Cox regression analysis, statin use was an independent factor associated with GC recurrence (adjusted hazard ratio (HR), 0.46; 95% confidence interval (CI), 0.26–0.82). Moreover, the risk of GC reduced with increasing duration (<3 years: HR 0.40, 95% CI 0.14–1.13; ≥3 years: HR 0.21, 95% CI 0.05–0.90; p trend = 0.011) and the dose of statin (cumulative defined daily dose (cDDD) < 500: HR 0.45, 95% CI 0.16–1.28; cDDD ≥ 500: HR 0.19, 95% CI 0.04–0.80; p trend = 0.008) in the propensity score-matched cohort. Statin use was associated with a lower risk of GC recurrence in H. pylori-negative patients with resected EGC in a dose-response relationship.
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Corvalan, Alejandro Hernan, Maria Jose Maturana, Wilda Olivares, Nicole Roldan, and Jacqueline Fry. "Inverse correlation between expression and methylation of RPRM, a TP53 dependent G2 arrest mediator candidate, along the gastric precancerous cascade." Journal of Clinical Oncology 34, no. 4_suppl (February 1, 2016): 73. http://dx.doi.org/10.1200/jco.2016.34.4_suppl.73.
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73 Background: Gastric cancer (GC) is one of first cause of cancer death worldwide. Lesions associated with the gastric precancerous cascade include atrophic gastritis (AG), intestinal metaplasia (IM), dysplasia (DY), and early (EGC)/advanced gastric cancer (AGC). Loss of expression due to aberrant methylation of Reprimo (RPRM), TP53 dependent G2 arrest mediator candidate, has been detected in patients with GC. Here we evaluated the methylation of the promoter region of RPRM in the precursor lesions. Methods: Fresh tissue biopsies from AG (N = 8), IM (N = 6), DY (N = 4), EGC (N = 5) and AGC (N = 8) were included. Expression and methylation levels of RPRM were detected by qPCR and MethyLight, respectively. Sequencing of 30 CpG sites of the promoter of RPRM was performed by Bisulfite sequencing. Results: Relative expression levels of the mRNA of RPRM decrease as gastric precancerous cascade progress, being significant in the transitions IM/DY and EGC/ACG. Methylation of the promoter of RPRM was detected in 4/8 AG, 3/6 IM, 4/4 DY, 5/5 EGC and 8/8 AGC. Spearman correlation analysis showed a significant inverse association between methylation and expression (r = -0.99, P < 0.0001). We observed increase of methylation of the CpG site 24 in the transition EGC to AGC. Conclusions: Our results show an inverse correlation between expression and methylation of RPRM along the gastric precancerous cascade. This inverse correlation is determinant in transitions from IM to DY and EGC to AGC. The identification of specific methylation of CpG site 24 associated EGC to AGC may be critical for the regulation of the RPRM expression. Grant Support: CONICYT-Fondap#15130011 and Fondecyt#1151411 from the Government of Chile
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Lu, Jun, Peng-yang Zhang, Jian-wei Xie, Jia-bin Wang, Jian-xian Lin, Qi-yue Chen, Long-long Cao, Ping Li, Chao-hui Zheng, and Chang-ming Huang. "Circular RNA hsa_circ_0006848 Related to Ribosomal Protein L6 Acts as a Novel Biomarker for Early Gastric Cancer." Disease Markers 2019 (September 2, 2019): 1–13. http://dx.doi.org/10.1155/2019/3863458.
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Objective. Circular RNAs (circRNAs) have been reported to be widely involved in pathological processes of various cancers. However, little is known about their diagnostic values in early gastric cancer (EGC). This study is aimed at exploring whether circulating circRNAs in plasma could act as biomarkers for EGC diagnosis. Materials and Methods. Mass spectrometry (MS) was performed to identify the proteins that at significantly aberrantly levels in gastric cancer (GC) tissues. The target circRNA was identified by bioinformatics analysis. A receiver operating characteristic (ROC) curve was generated to evaluate the diagnostic utility. Results. MS revealed that the ribosomal protein L6 (RPL6) expression was significantly downregulated only in EGC tissues vs. nontumorous tissues; this was validated by western blotting (n=30, p=0.0094). Bioinformatics analysis predicted that there is a hsa_circ_0006848/hsa_miR-329-5p/RPL6 axis in GC progression. The hsa_circ_0006848 expression was significantly downregulated in EGC tissues (vs. nontumorous tissues, n=30, p=0.0073) and plasma samples from EGC patients (vs. paired healthy volunteers, n=30, p=0.0089). In addition, the hsa_circ_0006848 plasma level in postoperative patients was significantly higher than that of preoperative patients (n=30, p=0.047). Furthermore, the decreased hsa_circ_0006848 expression in plasma was negatively correlated with poor differentiation (p=0.037) and tumor size (p=0.046). The area under the ROC curve (AUC) of hsa_circ_0006848 in plasma was 0.733, suggesting a good diagnostic value. The plasma hsa_circ_0006848 level combined with the carcinoembryonic antigen (CEA), carbohydrate-associated antigen 19-9 (CA19-9), and carbohydrate-associated antigen 72-4 (CA72-4) level increased the AUC to 0.825. Conclusion. Our results indicated that plasma hsa_circ_0006848 may be a novel noninvasive biomarker in EGC diagnosis.
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Alarcon, Alejandra, Wilda Olivares, Maria Jose Maturana, Andres Rodriguez, Oslando Padilla, Ignacio Alberto Wichmann, Alfonso Calvo, and Alejandro Corvalan. "Combined use of methylated reprimo cell-free DNA and pepsinogens for noninvasive detection of early gastric cancer." Journal of Clinical Oncology 33, no. 3_suppl (January 20, 2015): 27. http://dx.doi.org/10.1200/jco.2015.33.3_suppl.27.
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27 Background: Gastric cancer (GC) has been described as a multistep cascade of precursor lesions such as non-atrophic chronic gastritis (NACG), multiphocal atrophic gastritis (MAG), intestinal metaplasia (IM), low grade dysplasia (LGD) and high grade dysplasia (HGD) leading to early stages of GC (EGC). Currently, no non-invasive biomarkers for this progression are clinically available. We have previously identified a potential biomarker based on methylated Reprimo (RPRM) cell-free DNA (cfDNA) (Clin Cancer Res 2008;14:6264-9). In a cross-sectional study of 1,076 patients, we showed a sensitivity of 70.8% (95% CI: 60.3 to 81.3) and specificity of 74.3% (95% CI: 71.5 to 77) for methylated RPRM cfDNA, to distinguish NACG+MAG+IM+LGD vs HGD+EGC+AGC (Digestive Disease Week 2014 #108). However, the crude detection rate of EGC was only 46.6%. Here, we aim to explore the role of the combined use of methylated RPRM cfDNA and well stablished atrophy biomarkers such as pepsinogens, for non-invasive detection of EGC. Methods: A case-control study was performed including 237 patients (NACG:40; MAG:94; IM:55; LGD:11; HGD:5: EGC:15; AGC:17) scheduled for upper gastrointestinal endoscopy (UGIE). A heparinized venous blood sample was collected and methylated RPRM cfDNA and Immunoassays for Pepsinogen I and II were performed. Positive value was considered if methylated RPRM cfDNA > 0 copies/mL and PG I/II ratio <3.0 were found. Results: Overall sensitivity and specificity for the combined use of methylated RPRM cfDNA and PGI/II to distinguish NACG+MAG+IM+LGD vs HGD+EGC+AGC was 67.5% (95% CI: 50.2% to 81.9%) and 63% (95% CI: 55.9% to 69.7%), respectively. Positive and negative predictive values were 25.2% (95% CI: 17% to 34.9%) and 91.3% (95% CI: 85.3% to 95.4%), respectively. Importantly, crude detection rate for EGC increased from 46.6% to 86.7%. Conclusions: The combined use of methylated RPRM cfDNA and PGI/II reached similar sensitivity and specificity compared to methylated RPRM cfDNA alone to distinguish NACG+MAG+IM+LGD vs HGD+EGC+AGC. However, combined use of methylated RPRM cfDNA and PGI/II significantly improved the detection rate of EGC, a lesion with a curability rate over 95%.
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Zhang, Qing-Wei, Jin-Nan Chen, Zhao-Rong Tang, Yun-Jie Gao, Zhi-Zheng Ge, and Xiao-Bo Li. "Long- and short-term outcomes of early gastric cancer after endoscopic resection: a retrospective study from China." Endoscopy International Open 09, no. 07 (June 21, 2021): E1086—E1096. http://dx.doi.org/10.1055/a-1381-7013.
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Abstract Background and study aims The aim of the study was to evaluate short- and long-term outcomes of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in China because no study has yet been conducted to confirm its effectiveness in EGC in China. Patients and methods A total of 570 EGC samples from 537 patients were collected for evaluation of en bloc, complete, and curative resection using ESD. Data from 302 patients with at least 3 years of active follow-up were collected for analysis of recurrence of EGC and occurrence of metachronous GC (MGC). Short- and long-outcomes of mixed-type and pure differentiated EGC were also compared. Results En bloc resection rates of 96.0 %, 98.7 %, and 95.2 %, complete resection rates of 91.2 %, 96.6 % and 90.8 %, and curative resection rates of 83.0 %, 96.2 % and 88.2 % were achieved in all EGCs included in the study, those with absolute indication, and those with expanded indication, respectively. As a long-term outcome, recurrence was observed in 1.3 % of patients, 3-year and 5-year recurrence rates being 0.7 % and 1.2 %, respectively. Thirteen patients (4.3 %) exhibited MGCs during follow-up, all of which were resected in a second ESD. Conclusions The effectiveness of ESD for EGC in China was confirmed, with satisfactory short- and long-term outcomes. With scheduled follow-up, the outcomes for mixed-type EGC can be similar to those for pure differentiated EGC after complete resection without development of lymphovascular invasion.
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Klempner, Samuel Jacob, Joseph Chao, Mark Bailey, Seung Tae Kim, Jie He, Doron Lipson, Siraj Mahamed Ali, et al. "Genomic alterations (GA) predicted to confer lack of benefit from trastuzumab in advanced esophagogastric cancers (EGC): Analysis of 527 HER2-amplified (HER2amp) cases." Journal of Clinical Oncology 36, no. 4_suppl (February 1, 2018): 44. http://dx.doi.org/10.1200/jco.2018.36.4_suppl.44.
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44 Background: The addition of trastuzumab to chemotherapy improves survival in first line treatment of advanced HER2 overexpressing EGC. However, the response rate is under 50% in this molecularly heterogeneous group of cancers. Genomic alterations (GA) associated with lack of benefit from trastuzumab are understudied. Methods: We prospectively analyzed clinical samples from patients with EGC using hybrid-capture based comprehensive genomic profiling (CGP). Pre-specified literature review was used to determine GA associated with de-novo trastuzumab resistance. Results: From 2,245 gastroesophageal junction (GEJ) adenocarcinomas and 1,883 gastric adenocarcinomas (GC) we identified 395 HER 2-amplified GEJ (18%) and 132 HER 2-amplified (HER2amp) GC (7.0%) cases. Median HER 2 copy number was 19 in GEJ and 16 in GC samples. PIK3CA GA and METamp were observed in ~9% and ~5% of both HER 2amp and non- HER2amp EGC cases; however, co-amplification of cell-cycle mediators CDK6 and CCCNE1 were each significantly enriched in HER 2amp cases (Table). MYCamp and deleterious SMAD4 GA were also significantly enriched in cases with Her2amp. CDKN2A GA were common regardless of HER 2amp, particularly in GEJ . In cases with >100 estimated HER 2 copies, only PIK3CA GA were significantly less frequent than in those with 6-99 copies (2.3% vs. 9.8%, P =0.04). All HER 2amp cases were microsatellite stable. A clinically annotated HER 2amp cohort will be presented. Conclusions: GA predicted to decrease trastuzumab sensitivity exist in a significant portion of HER 2amp EGC, although not all are enriched relative to non- HER 2amp cases. CGP may provide additive information to traditional HER2 testing and identify patients less likely to benefit from therapy. Larger clinical datasets are needed to validate our observations. [Table: see text]
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Li, Ming. "A Class of Negatively Fractal Dimensional Gaussian Random Functions." Mathematical Problems in Engineering 2011 (2011): 1–18. http://dx.doi.org/10.1155/2011/291028.
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Letx(t)be a locally self-similar Gaussian random function. Denote byrxx(τ)the autocorrelation function (ACF) ofx(t). Forx(t)that is sufficiently smooth on(0,∞), there is an asymptotic expression given byrxx(0)-rxx(τ)~c|τ|αfor|τ|→0, wherecis a constant andαis the fractal index ofx(t). If the above is true, the fractal dimension ofx(t), denoted byD, is given byD=D(α)=2−α/2. Conventionally,αis strictly restricted to0<α≤2so as to make sure thatD∈[1,2). The generalized Cauchy (GC) process is an instance of this type of random functions. Another instance is fractional Brownian motion (fBm) and its increment process, that is, fractional Gaussian noise (fGn), which strictly follow the case ofD∈[1,2)or0<α≤2. In this paper, I claim that the fractal indexαofx(t)may be relaxed to the rangeα>0as long as its ACF keeps valid forα>0. With this claim, I extend the GC process to allowα>0and call this extension, for simplicity, the extended GC (EGC for short) process. I will address that there are dimensions0≤D(α)<1for2<α≤4and furtherD(α)<0for4<αfor the EGC processes. I will explain thatx(t)with1≤D<2is locally rougher than that with0≤D<1. Moreover,x(t)withD<0is locally smoother than that with0≤D<1. The local smoothestx(t)occurs in the limitD→−∞. The focus of this paper is on the fractal dimensions of random functions. The EGC processes presented in this paper can be either long-range dependent (LRD) or short-range dependent (SRD). Though applications of such class of random functions forD<1remain unknown, I will demonstrate the realizations of the EGC processes forD<1. The above result regarding negatively fractal dimension on random functions can be further extended to describe a class of random fields with negative dimensions, which are also briefed in this paper.
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Yang, Liangwei, Yu Yu, Xiuchong Yu, Jiaming Zhou, Zhiping Zhang, Shibo Ying, Junming Guo, and Zhilong Yan. "Downregulated Expression of hsa_circ_0005556 in Gastric Cancer and Its Clinical Significance." Disease Markers 2019 (November 19, 2019): 1–7. http://dx.doi.org/10.1155/2019/2624586.
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Background. Gastric cancer (GC) has a poor prognosis due to the lack of ideal tumor markers. Circular RNAs (circRNAs) are a novel type of noncoding RNA related to the occurrence of GC. Among our research, we investigated the role of hsa_circ_0005556 in GC. Materials and Methods. The expression of hsa_circ_0005556 of 100 paired GC tissues and adjacent normal tissues was detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). A receiver operating characteristic (ROC) curve was established to evaluate the diagnostic value of hsa_circ_0005556. The correlation between the expression of hsa_circ_0005556 and corresponding clinicopathological characteristic was explored. Results. hsa_circ_0005556 was significantly downregulated in GC tissues contrasted with adjacent normal tissues (n=100, p<0.001). The areas under the ROC curve (AUC) of hsa_circ_0005556 were up to 0.773, while 64% sensitivity and 82% specificity, respectively. Moreover, its expression levels were significantly associated with differentiation (p=0.001), TNM stage (p=0.013), and lymphatic metastasis (p=0.039). GC patients of high hsa_circ_0005556 levels had a longer overall survival (OS) than those of the low group (p=0.047). Conclusion. hsa_circ_0005556 is a potential biomarker for GC, which may guide judgment of the indication of endoscopic treatment for early gastric cancer (EGC).
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Ze Xu, Jin, Sai Ying Venus Yeung, Qi Chang, Yu Huang, and Zhen-Yu Chen. "Comparison of antioxidant activity and bioavailability of tea epicatechins with their epimers." British Journal of Nutrition 91, no. 6 (June 2004): 873–81. http://dx.doi.org/10.1079/bjn20041132.
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Canned and bottled tea drinks contain not only green tea epicatechins (GTE), namely (−)-epigallocatechin gallate (EGCG), (−)-epicatechin gallate (ECG), (−)-epigallocatechin (EGC) and (−)-epicatechin (EC), but also four GTE epimers, namely (−)-gallocatechin gallate (GCG), (−)-catechin gallate (CG), (−)-gallocatechin (GC) and (−)-catechin (C). In the present study we examined the antioxidant activity and bioavailability of these epimers compared with their corresponding precursors. The epimerisation reaction was induced by autoclaving GTE extract derived from longjing green tea at 120°C for 20 min. Isolation and purification of each GTE and epimer were accomplished by various column chromatographic and semi-preparative HPLC techniques. The antioxidant activity of each epimer with its corresponding GTE precursor was conducted in the three in vitro systems, namely human LDL oxidation, ferric reducing–antioxidant power (FRAP), and anti-2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical assays. The results of all three assays demonstrated that CG had similar antioxidant activity with its precursor ECG, while GC was less potent as an antioxidant than its precursor EGC. Regarding EGCG and GCG, the antioxidant potency was similar for both LDL oxidation and DPPH free radical assays, but GCG was statistically less effective than EGCG in the FRAP assay. For EC and C, the latter had less anti-free radical activity in the DPPH assay, but in LDL oxidation and FRAP assays the antioxidant activity was similar. Oral and intravenous dosing of GTE–epimer mixture led to increase in total plasma antioxidant capacity in rats. In general, both epicatechins and epimers had low bioavailability (0·08–0·31) and most of the observed differences between epicatechins and their corresponding epimers were small, even if they were statistically significant in some cases. It was concluded that the epimerisation reaction occurring in manufacturing canned and bottled tea drinks would not significantly affect antioxidant activity and bioavailability of total tea polyphenols.
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KC, Santosh, Meiya Liu, Qunfeng Zhang, Kai Fan, Yuanzhi Shi, and Jianyun Ruan. "Metabolic Changes of Amino Acids and Flavonoids in Tea Plants in Response to Inorganic Phosphate Limitation." International Journal of Molecular Sciences 19, no. 11 (November 21, 2018): 3683. http://dx.doi.org/10.3390/ijms19113683.
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The qualities of tea (Camellia sinensis) are not clearly understood in terms of integrated leading molecular regulatory network mechanisms behind inorganic phosphate (Pi) limitation. Thus, the present work aims to elucidate transcription factor-dependent responses of quality-related metabolites and the expression of genes to phosphate (P) starvation. The tea plant organs were subjected to metabolomics analysis by GC×GC-TOF/MS and UPLC-Q-TOF/MS along with transcription factors and 13 metabolic genes by qRT-PCR. We found P starvation upregulated SPX2 and the change response of Pi is highly dependent on young shoots. This led to increased change in abundance of carbohydrates (fructose and glucose), amino acids in leaves (threonine and methionine), and root (phenylalanine, alanine, tryptophan, and tyrosine). Flavonoids and their glycosides accumulated in leaves and root exposed to P limitation was consistent with the upregulated expression of anthocyanidin reductase (EC 1.3.1.77), leucoanthocyanidin dioxygenase (EC 1.4.11.19) and glycosyltransferases (UGT78D1, UGT78D2 and UGT57L12). Despite the similar kinetics and high correlation response of Pi and SPX2 in young shoots, predominating theanine and other amino acids (serine, threonine, glutamate, valine, methionine, phenylalanine) and catechin (EGC, EGCG and CG) content displayed opposite changes in response to Pi limitation between Fengqing and Longjing-43 tea cultivars.
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AFIFY, Abd El-Moneim M. R., Emad A. SHALABY, and Hossam Saad EL-BELTAGI. "Antioxidant Activity of Aqueous Extracts of Different Caffeine Products." Notulae Botanicae Horti Agrobotanici Cluj-Napoca 39, no. 2 (November 21, 2011): 117. http://dx.doi.org/10.15835/nbha3926254.
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The antioxidant activity of water extracts (cold and hot) of six caffeine products were carried out. The extracts were screened for total polyphenol contents and antioxidant activity using DPPH, ABTS methods and reducing power method at 50 and 100 μg/ml after 15 min and 30 min using DPPH, ABTS BHA and Caffeine as standard compounds. The results indicated that, the hot water extracts for different caffeine products showed higher antioxidant activity than those of cold extracts and this activity was time and concentration dependent. In addition, the activity was higher against ABTS radical more than DPPH and reducing power methods. Also, there is a positive correlation between the antioxidant and reducing compounds presented in water extracts of different caffeine products. The results of HPLC showed that fresh tea leaves are rich in flavanol monomers known as catechins. The most abundant catechin derivatives in green tea are EGC, EGCG and GC. On the other hand EGCG and GC are major catechin derivative in different caffeine product except El-Fakher tea and Cacao. Generally, these beverages had high antioxidant capacities and total phenolic contents, and could be important dietary sources of antioxidant phenolic for prevention of diseases caused by oxidative stress.
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Ai, Zeyi, Shuyuan Liu, Fengfeng Qu, Haojie Zhang, Yuqiong Chen, and Dejiang Ni. "Effect of Stereochemical Configuration on the Transport and Metabolism of Catechins from Green Tea across Caco-2 Monolayers." Molecules 24, no. 6 (March 26, 2019): 1185. http://dx.doi.org/10.3390/molecules24061185.
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The transcellular transport and metabolism of eight green tea catechins (GTCs) were studied in Caco-2 monolayers, with the aim of investigating the effect of cis–trans isomerism on the membrane permeability and biotransformation of GTCs. The results showed that the catechin stereochemistry significantly affects the efflux transport rather than the absorption transport in the Caco-2 monolayers. The trans catechins showed a better transcellular permeability than their corresponding cis (epi) catechins in the efflux transport, as the efflux amount of trans catechins were all significantly higher than that of the cis (epi) catechins at each concentration and each time point tested. Moreover, the relative contents of the (+)-catechin (C)-O-sulfate, (+)-gallocatechin (GC)-O-sulfate, (−)-catechin gallate (CG)-O-sulfate, and (−)-gallocatechin gallate (GCG)-O-sulfate in the efflux transport were 2.67, 16.08, 50.48, and 31.54 times higher than that of the (−)-epicatechin (EC)-O-sulfate, (−)-epigallocatechin (EGC)-O-sulfate, (−)-epicatechin gallate (ECG)-O-sulfate, and (−)-epigallocatechin gallate (EGCG)-O-sulfate, respectively. It indicated that more metabolites were observed after the transcellular efflux of trans catechins. Furthermore, after two hours of incubation, the GTCs could significantly increase the expression of multidrug resistance-associated protein 2 (MRP2) and breast cancer-resistance protein (BCRP), and decrease the expression of P-glycoprotein in the Caco-2 cells. The regulation of GTCs on P-glycoprotein, MRP2, and BCRP could also be significantly influenced by the chemical and dimensional structure. In a conclusion, catechin stereochemistry significantly affects the transport and metabolism of GTCs when refluxed in the Caco-2 monolayers.
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Masler, E. P. "Effects of catechin polyphenols and preparations from the plant–parasitic nematode Heterodera glycines on protease activity and behaviour in three nematode species." Journal of Helminthology 88, no. 3 (May 2, 2013): 349–56. http://dx.doi.org/10.1017/s0022149x13000254.
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AbstractProtease activities in preparations from the plant-parasitic nematodes Heterodera glycines and Meloidogyneincognita and the free-living nematode Panagrellus redivivus were inhibited by exposure to a series of eight catechin polyphenol analogues, (+)-catechin, ( − )-epicatechin (EC), ( − )-gallocatechin (GC), ( − )-epigallocatechin (EGC), ( − )-catechin gallate (CG), ( − )-gallocatechin gallate (GCG), ( − )-epicatechin gallate (ECG) and ( − )-epigallocatechin gallate (EGCG) (1 mm each), and by a preparation from H. glycines cysts. General protease activity detected with the FRET-peptide substrate QXL520-KSAYMRF-K(5-FAM)a and proteasome chymotrypsin-like (CTL) activity detected with succinyl-LLVY-AMC were each inhibited significantly more (P< 0.05) by the gallated form of the polyphenol than by the corresponding non-gallated form. Species differences in response to inhibition across all analogues were revealed with the CTL substrate, but CG was a consistently potent inhibitor across all three species and with each substrate. A heat-stable component (CE) from H. glycines cysts inhibited M. incognita CTL activity by 92.07 ± 0.68%, significantly less (P< 0.05) in H. glycines (52.86 ± 2.77%), and by only 17.24 ± 0.55% (P< 0.05) in P. redivivus preparations. CTL activity was, however, inhibited more than 60% in all preparations by the proteasome-specific inhibitor MG-132. Hatching of M. incognita infective juveniles exposed to 1 mm CG, ECG, GCG or EGCG was reduced by 83.88 ± 4.26%, 69.98 ± 9.14%, 94.93 ± 1.71% and 87.93 ± 2.89%, respectively, while hatching of H. glycines was reduced less than 25% by each analogue. CE had no effect on nematode hatch, but did cause a 60% reduction in mobility of H. glycines infective juveniles exposed overnight to CE in vitro, which was more (P< 0.05) than the reduction of M. incognita infective juvenile mobility (20%).
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Narita, Yukiya, Hiroko Hasegawa, Azusa Komori, Seiichiro Mitani, Toshiki Masuishi, Hiroya Taniguchi, Shigenori Kadowaki, et al. "Survival outcome of metastatic adenocarcinoma of esophagogastric junction in the trastuzumab era." Journal of Clinical Oncology 34, no. 4_suppl (February 1, 2016): 117. http://dx.doi.org/10.1200/jco.2016.34.4_suppl.117.
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117 Background: Previous studies have reported no differences in treatment outcomes between metastatic adenocarcinoma esophagogastric junction (AEGJ) and gastric adenocarcinoma (GAC). However, after the approval of trastuzumab (Tmab) for the treatment of metastatic AEGJ and GAC survival outcomes remain unclear. Methods: We retrospectively reviewed clinicopathological characteristics, treatment outcomes, and prognoses of 289 consecutive patients with AEGJ and GAC who received first-line chemotherapy from March 2011, when Tmab was approved in Japan, to December 2013 at Aichi Cancer Center Hospital. Prognostic factors were identified using Cox multivariate regression analysis. IHC3+ or IHC2+/ISH+ tumors were defined as HER2 positive. Results: Of 289 patients, 45 (16%) had AEGJ. Patients with AEGJ were significantly younger with lesser lung metastases than those with GAC. HER2-positive rates in AEGJ tended to be greater than those in GAC, but this difference was not statistically significant (22% vs. 16%; P = 0.35). The rates of platinum doublet therapies were not significantly different (72% vs. 78%; P = 0.47). The objective response rate (ORR) was 27% with AEGJ and 40% with GAC (P = 0.17). The median follow-up duration was 12.1 and 11.9 months, respectively. Progression-free survival was similar for both the groups [hazard ration (HR) = 0.97; P = 0.83), while the median overall survival (OS) period was numerically longer for AEGJ than that for GC (14.7 vs. 12.4 months; HR = 0.99; 95% confidence interval = 0.69–1.39; P = 0.92). In patients with AEGJ, an ECOG performance status of 2 and HER2 negativity were significantly associated with poor prognosis, as estimated by the multivariate analyses of OS. The analyses that were limited to patients treated with Tmab as the first-line chemotherapy revealed no significant differences in ORR and median OS between AEGJ and GAC. Conclusions: Even in the Tmab era, there were no significant differences in survival outcomes between metastatic EGC and GAC.
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An, Fangmei, Chuwei Zheng, Guoqiang Zhang, Liangyun Zhou, Yuqing Wu, Zheng Hou, Zhiyi Zhou, Ke Chen, and Qiang Zhan. "Carcinoembryonic Antigen Related Cell Adhesion Molecule 6 Promotes Carcinogenesis of Gastric Cancer and Anti-CEACAM6 Fluorescent Probe Can Diagnose the Precancerous Lesions." Frontiers in Oncology 11 (June 17, 2021). http://dx.doi.org/10.3389/fonc.2021.643669.
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The diagnosis of precancerous lesions or early gastric cancer (EGC) is very important for patient survival. Molecular imaging is a visualized method that can easily and precisely diagnose tumors. However, there are currently few studies about molecular imaging diagnosis of EGC. Here, we studied the expression of carcinoembryonic antigen related cell adhesion molecule 6 (CEACAM6) in the progression of GC. Then, the regulatory roles of CEACAM6 in GC cells were investigated. Furthermore, both the fluorescent-labeled and near infrared molecular-labeled probes were synthesized, and the diagnostic value of anti-CEACAM6 probes in GC was evaluated in vivo using a GC mice model as well as in vitro using fresh dysplastic gastric mucosa obtained from endoscopic submucosal dissection (ESD) operations. Our study showed that CEACAM6 was over expressed in GC tissues compared to adjacent tissues, and the patients with higher CEACAM6 expression had lower survival time. Moreover, the CEACAM6 expression was higher in the dysplastic gastric mucosa than in the adjacent normal mucosa. CEACAM6 accelerated the growth, proliferation, and invasion of GC cells in the in vitro and in vivo studies. Moreover, up regulated CEACAM6 can induce the expression of proteins related to GC progression. Furthermore, the anti-CEACAM6 probes exhibited good affinity with GC cell lines. The probes can track tumors as well as metastases in the mice model in vivo, and can precisely identify the area of dysplastic gastric mucosa using specimens obtained from ESD operations by wide field fluorescent endoscopy. The surface micro features of the mucosa can also be observed using fluorescent micro endoscopy, and the degree of atypia can be distinguished by both the signal intensity and surface micro morphology. CEACAM6 is a key molecular marker in GC progression, and the anti-CEACAM6 probe-assisted fluorescent endoscopy may be a potential option for the diagnosis of precancerous lesions.
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Zhu, Yue, and De-Yu Xie. "Docking Characterization and in vitro Inhibitory Activity of Flavan-3-ols and Dimeric Proanthocyanidins Against the Main Protease Activity of SARS-Cov-2." Frontiers in Plant Science 11 (November 30, 2020). http://dx.doi.org/10.3389/fpls.2020.601316.
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We report to use the main protease (Mpro) of SARS-Cov-2 to screen plant flavan-3-ols and proanthocyanidins. Twelve compounds, (–)-afzelechin (AF), (–)-epiafzelechin (EAF), (+)-catechin (CA), (–)-epicatechin (EC), (+)-gallocatechin (GC), (–)-epigallocatechin (EGC), (+)-catechin-3-O-gallate (CAG), (–)-epicatechin-3-O-gallate (ECG), (–)-gallocatechin-3-O-gallate (GCG), (–)-epigallocatechin-3-O-gallate (EGCG), procyanidin A2 (PA2), and procyanidin B2 (PB2), were selected for docking simulation. The resulting data predicted that all 12 metabolites could bind to Mpro. The affinity scores of PA2 and PB2 were predicted to be −9.2, followed by ECG, GCG, EGCG, and CAG, −8.3 to −8.7, and then six flavan-3-ol aglycones, −7.0 to −7.7. Docking characterization predicted that these compounds bound to three or four subsites (S1, S1′, S2, and S4) in the binding pocket of Mpro via different spatial ways and various formation of one to four hydrogen bonds. In vitro analysis with 10 available compounds showed that CAG, ECG, GCG, EGCG, and PB2 inhibited the Mpro activity with an IC50 value, 2.98 ± 0.21, 5.21 ± 0.5, 6.38 ± 0.5, 7.51 ± 0.21, and 75.3 ± 1.29 μM, respectively, while CA, EC, EGC, GC, and PA2 did not have inhibitory activities. To further substantiate the inhibitory activities, extracts prepared from green tea (GT), two muscadine grapes (MG), cacao, and dark chocolate (DC), which are rich in CAG, ECG, GAG, EGCG, or/and PB2, were used for inhibitory assay. The resulting data showed that GT, two MG, cacao, and DC extracts inhibited the Mpro activity with an IC50 value, 2.84 ± 0.25, 29.54 ± 0.41, 29.93 ± 0.83, 153.3 ± 47.3, and 256.39 ± 66.3 μg/ml, respectively. These findings indicate that on the one hand, the structural features of flavan-3-ols are closely associated with the affinity scores; on the other hand, the galloylation and oligomeric types of flavan-3-ols are critical in creating the inhibitory activity against the Mpro activity.
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Shori, Amal Bakr, Premalatha Muniandy, and Ahmad Salihin Baba. "Changes in Phenolic Compounds Profiles in Tea Extracts and the Composition of these Phenolic Compounds in Yogurt." Recent Patents on Food, Nutrition & Agriculture 11 (November 23, 2020). http://dx.doi.org/10.2174/2212798411999201123205022.
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Background:: Green, white, and black tea water extracts are rich in phenolic compounds. Objective:: The changes in phenolic compounds profiles of green, white, and black tea (GT, WT, & BT respectively) water extracts and their respective yogurt were investigated. Method:: Three types of yogurt with tea water extracts were prepared and the phenolic compounds profiles were analyzed using liquid chromatography mass spectrometry (LC-MS) method. Results:: The present data found that flavonol glycosides such as kaempferol-3-rutinoside and quercetin-rhamnosylgalactoside or rutinoside were present in WT extract whereas catechin derivatives such as gallocatechin (GC) and epigallocatechin (EGC) were present in GT extract. Moreover, theaflavin-3-O-gallate was observed in BT extract. Many of the catechin and its derivatives detected in the tea extracts were not identified in the tea yogurt samples. However, new phenolic compounds were present in GT-yogurt (i.e. kaempferol-3- rutinoside and quinic acid conjugate) but absent in GT extract. Conclusion:: GT, WT, & BT extracts could be used to enriched-yogurt with phenolic compounds which may have antioxidant properties.
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Sugimoto, Ryo, Masaki Endo, Mitsumasa Osakabe, Yosuke Toya, Naoki Yanagawa, Takayuki Matsumoto, and Tamotsu Sugai. "Immunohistochemical Analysis of Mismatch Repair Gene Proteins in Early Gastric Cancer Based on Microsatellite Status." Digestion, October 14, 2020, 1–10. http://dx.doi.org/10.1159/000510679.
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<b><i>Background:</i></b> Microsatellite instability (MSI) is a major pathway involved in gastric carcinogenesis and is observed in 10–20% of early gastric cancers (EGCs). Early detection of EGCs with an MSI-high phenotype would be useful for elucidating the mechanisms of gastric carcinogenesis and improving outcomes in patients with GC. <b><i>Objective:</i></b> We explored the usefulness of immunohistochemical expression of mismatch repair (MMR) proteins, including MLH1, PMS2, MSH2, and MSH6 in EGC. <b><i>Methods:</i></b> We examined the expression of 4 MMR proteins using immunohistochemistry in 119 patients with EGC based on MS status, as determined by polymerase chain reaction-microsatellite analysis. In addition, methylation of the <i>MLH1</i> gene was quantified by pyrosequencing. <b><i>Results:</i></b> EGCs were classified into 46 MSI-high phenotypes and 73 microsatellite stable (MSS) phenotypes. Although loss of MLH1 expression was associated with loss of PMS2 expression in the MSI-high phenotype, discordant cases of loss of expression between MLH1 and PMS2 were found (MLH1 [−]/PMS2 [+], 3 cases). Loss of MLH1/PMS2 expression was observed in 2 of 73 MSS phenotypes. Loss of MSH2/MSH6 expression was found in 4 of 46 MSI-high phenotypes, whereas loss of MSH2/MSH6 expression was not detected in the MSS phenotype. In addition, loss of MLH1 expression was correlated with methylation of <i>MLH1</i>. However, there were discordant cases in which loss of MLH1 expression was not accompanied by methylation of <i>MLH1</i>. <b><i>Conclusion:</i></b> Although immunostaining of MMR proteins could help predict MSI in EGCs, immunostaining did not have the same value as genetic testing for determination of MSI.
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Dewi Anjarsari, Intan Ratna. "Katekin teh Indonesia : prospek dan manfaatnya." Kultivasi 15, no. 2 (August 30, 2016). http://dx.doi.org/10.24198/kltv.v15i2.11871.
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Teh Indonesia dikenal karena memiliki kandungan katekin (antioksidan alami) tertinggi di dunia Katekin adalah salah satu turunan dari poliphenol yang memiliki khasiat antioxidant yang tinggi. Faktor yang mempengaruhi kadar katekin adalah varietas dan klon teh, ketinggian tempat, umur daun, serta jenis petikan. Dipandang dari sisi kesehatan, makin tinggi katekin berarti makin bermanfaat buat kesehatan. Akan tetapi sebaliknya, ditinjau dari sisi rasa, memiliki perbandingan yang terbalik. Katekin berperan penting di dalam menentukan aroma dan rasa. Katekin merupakan senyawa tidak berwarna dan larut dalam air serta membawa sifat pahit dan sepat pada seduhan teh. Senyawa ini paling penting dalam daun teh karena dapat menentukan kualitas teh dalam pengolahanya. Katekin dalam teh merupakan senyawa kompleks yang tersusun atas epikatekin (EC), epikatekin galat (ECG), epigalokatekin (EGC), epigalokatekin galat (EGCG), dan galokatekin (GC). Komponen yang mendominasi yaitu epigalokatekin dan epigalokatekin galat. Kandungan katekin berkisar antara 20-30% dari seluruh berat kering daun. Dalam pengolahan, secara langsung atau tidak langsung, perubahan katekin selalu dihubungkan dengan semua sifat teh jadi, yaitu rasa, warna, dan aroma. Katekin yang mendominasi 20% berat kering teh merupakan substansi utama yang menyebabkan teh memenuhi persyaratan sebagai minuman fungsional Kata kunci : katekin, poliphenol, minuman fungsional
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Dewi Anjarsari, Intan Ratna. "Katekin teh Indonesia : prospek dan manfaatnya." Kultivasi 15, no. 2 (August 30, 2016). http://dx.doi.org/10.24198/kultivasi.v15i2.11871.
Full textAbstract:
Teh Indonesia dikenal karena memiliki kandungan katekin (antioksidan alami) tertinggi di dunia Katekin adalah salah satu turunan dari poliphenol yang memiliki khasiat antioxidant yang tinggi. Faktor yang mempengaruhi kadar katekin adalah varietas dan klon teh, ketinggian tempat, umur daun, serta jenis petikan. Dipandang dari sisi kesehatan, makin tinggi katekin berarti makin bermanfaat buat kesehatan. Akan tetapi sebaliknya, ditinjau dari sisi rasa, memiliki perbandingan yang terbalik. Katekin berperan penting di dalam menentukan aroma dan rasa. Katekin merupakan senyawa tidak berwarna dan larut dalam air serta membawa sifat pahit dan sepat pada seduhan teh. Senyawa ini paling penting dalam daun teh karena dapat menentukan kualitas teh dalam pengolahanya. Katekin dalam teh merupakan senyawa kompleks yang tersusun atas epikatekin (EC), epikatekin galat (ECG), epigalokatekin (EGC), epigalokatekin galat (EGCG), dan galokatekin (GC). Komponen yang mendominasi yaitu epigalokatekin dan epigalokatekin galat. Kandungan katekin berkisar antara 20-30% dari seluruh berat kering daun. Dalam pengolahan, secara langsung atau tidak langsung, perubahan katekin selalu dihubungkan dengan semua sifat teh jadi, yaitu rasa, warna, dan aroma. Katekin yang mendominasi 20% berat kering teh merupakan substansi utama yang menyebabkan teh memenuhi persyaratan sebagai minuman fungsional Kata kunci : katekin, poliphenol, minuman fungsional