The inhibitory effect of resveratrol on the growth of gastric cancer cells through downregulation of the Wnt/β-catenin signaling pathway were studied. First we determined the effective concentration of resveratrol on the growth and proliferation of MGC-803 gastric cancer cells. Methylthiazolyl tetrazolium assay showed that resveratrol significantly inhibited the proliferation of MGC-803 cells in a dose-dependent manner. Resveratrol induced apoptotic morphological changes in MGC-803 cells. Reverse transcription-polymerase chain reaction and western blot analysis showed that resveratrol downregulated the expression of three important components of the Wnt signaling pathway, β-catenin, c-myc, and cyclin D1, at the mRNA and protein levels. Overall, resveratrol inhibits the growth of MGC-803 cells by inhibiting the Wnt signaling pathway. This study provides a new idea and direction for the antitumor mechanism of resveratrol.
Background Congenital shunt location is related to Eisenmenger syndrome (ES) survival. Moreover, right ventricular (RV) remodeling is associated with poor survival in pulmonary hypertension. Purpose To investigate RV remodeling using comprehensive magnetic resonance imaging (MRI) techniques and identify its relationship with prognosis in ES subgroups classified by shunt location. Study Type Prospective observational study. Population Fifty‐four adults with ES (16 with pre‐tricuspid shunt and 38 with post‐tricuspid shunt). Field Strength/Sequence 3.0 T/cine MRI with balanced steady‐state free precession sequence, late gadolinium enhancement with inversion recovery segmented gradient echo sequence and phase‐sensitive reconstruction, and T1 mapping with modified Look‐Locker inversion recovery sequence. Assessment Demographics, clinical characteristics, hemodynamics, RV remodeling features (morphology, systolic function, RV–pulmonary artery (PA) coupling and myocardial fibrosis), and prognosis were compared between ES subgroups. The adverse endpoint was all‐cause mortality or readmission for heart failure. Statistical Tests The independent samples t‐test, Fisher's exact test or Chi‐squared test, and the Kaplan–Meier method were used. P < 0.05 was considered significant. Results Compared to patients with post‐tricuspid shunt, patients with pre‐tricuspid shunt were significantly older and had higher N‐terminal pro‐B‐type natriuretic peptide concentrations and poorer exercise tolerance. Pre‐tricuspid shunt showed significantly larger RV dimensions (end‐diastolic volume index: 185.81 ± 37.49 vs. 98.20 ± 36.26 mL/m2), worse RV ejection fraction (23.54% ± 12.35% vs. 40.82% ± 10.77%), and RV–PA decoupling (0.35 ± 0.31 vs. 0.72 ± 0.29). Biventricular myocardial fibrosis was significantly more severe in pre‐tricuspid shunt than post‐tricuspid shunt (extracellular volume, left ventricle: 35.85% ± 2.58% vs. 29.10% ± 5.20%; RV free wall: 30.93% ± 5.65% vs. 26.75% ± 5.15%). In addition, pre‐tricuspid shunt demonstrated a significantly increased risk of adverse endpoint (hazard ratio: 2.938, 95% confidence interval: 1.204–7.172). Data Conclusion ES with pre‐tricuspid shunt might be a unique subtype with worse clinically decompensated RV remodeling and poor prognosis. Level of Evidence: 2 Technical Efficacy Stage: 5
Colorectal cancer is very common worldwide and advanced colorectal cancer exhibited very poor clinical outcome. Oxaliplatin (OXP) is one of the principal chemotherapeutic agents in colorectal cancer treatment presenting impressive anti-tumor ability, limited by adverse effect in clinical practice. Fibrin glue (FG) is a biocompatible formulation made of fibrinogen and thrombin, extensively used in surgery for hemostasis, tissue adhesion and sealing. In this study, FG was innovatively applied as OXP delivery system and results showed enhanced anti-tumor performance in subcutaneous model and abdominal metastasis model of murine colorectal cancer compared with that of OXP used alone. It is revealed that combination of OXP and FG could increase activated CD8+ T cells, reduce regulatory T (Treg) cells and increase interferon-γ (IFN-γ). Furthermore, results showed promoted tumor apoptosis, decreased proliferation and inhibited tumor angiogenesis by OXP and FG combination. No obvious systemic toxicity was observed in this study. Finally, our findings provided basis for promising application of OXP and FG combination in colorectal cancer treatment.
In our previous studies, we discovered the congenital cold syndrome (CCS), which is characterized by ‘qi deficiency and qi stagnation, mixed cold and heat.’ And there is a type of syndrome with special incidence characteristic. However, the diagnosis of CCS still lacks an objective basis. In this study, we performed Tandem Mass Tag (TMT) based on quantitative proteomics technology to screen the significantly differentially expressed proteins (DEPs) in serum of patients with coronary heart disease (CHD) patients with CCS, patients with heart and kidney yang deficiency, and healthy people. A total of 22 DEPs (nine upregulated and 13 downregulated) were identified between patients with CCS and healthy subjects. Next, we performed GO and KEGG pathway enrichment analysis, we found the primary functions of DEPs of CCS were binding, catalytic activity, and molecular function regulator. These DEPs were mainly involved in important biological processes, such as cellular process, response to stimulus, localization, metabolic process, and biological regulation. The KEGG analysis revealed that the DEPs showed significant changes in fructose and mannose metabolism, Pentose phosphate pathway, and Arrhythmogenic right ventricular cardiomyopathy. After parallel reaction monitoring (PRM) verification, four upregulated target proteins (ALDOA, PCYOX1, Crisp3 and IGLV4-69) and three downregulated proteins (ALDOC, ADAMTSL-2 and C3) were accurately identified. These proteins were mainly related to immune response and glucose metabolism. These DEPs could be the marker proteins of coronary heart disease with CCS. This findings help to reveal the pathogenesis of CHD with CCS and provide potential therapeutic targets.
2505 Background: Human carbonyl reductase 3 (CBR3) is one of the main metabolizing enzymes to extensively reduce doxorubicin to its major active metabolite, doxorubicinol in normal and tumor tissues. Recently, the CBR3 958G>A (V244M) genetic variant has been described to alter function in vitro. We postulate that CBR3 genetic variants could contribute to the inter-individual variability of doxorubicin pharmacokinetics in breast cancer patients. Methods: We studied 101 female breast cancer patients (66 Chinese, 26 Malay, 7 Indian and 2 of other ethnic origins) who were treated with doxorubicin at 75mg/m2 every 3 weeks. Comprehensive sequencing of the 3 exons of CBR3, including the splice-site junctions was performed. Plasma concentrations of doxorubicin and doxorubicinol were analyzed during the first doxorubicin cycle. Results: Five CBR3 coding region variants (239G>A, 483C>T, 507C>T, 598G>A and 958G>A) were detected, of which 239G>A, 598G>A and 958G>A were non-synonymous. 598G>A was novel, and was found in 1 Malay patient who was heterozygous. The genotype distributions of 239G>A and 958G>A were 36%/30%/34%, and 40%/36%/24% respectively for GG/AG/AA. The 239GG variant was associated with significantly higher AUC of doxorubicinol and AUC ratio of doxorubicinol to doxorubicin than the AG and AA variants (AUC of doxorubicinol 2.18±1.37ug/ml*h (GG) vs 2.04±2.11ug/ml*h (AG), p=0.05, and 1.55±0.61ug/ml*h (AA), p=0.004; AUC ratio of doxorubicinol to doxorubicin 1.90±1.29 (GG) vs 1.72±1.34 (AG), p=0.025, and 1.45±0.67 (AA), p=0.006). Patients with the 958AA variant had significantly higher AUC of doxorubicinol than those with the 958GG variant (2.29±1.60ug/ml*h vs 1.56±0.60ug/ml*h, p=0.009). The 239GG variant was more common in our population than in Caucasians (36% vs 20%. p=0.027), while the 958AA variant was more common than reported in Caucasians (24% vs 8%, p=0.014) and Japanese (24% vs 7%, p=0.016). Conclusions: CBR3 genetic variants may influence the pharmacokinetics of doxorubicin and its major metabolite doxorubicinol. Inter-ethnic differences in frequencies of CBR3 genetic variants exist and may account for differences in pharmacokinetics and pharmacodynamics of doxorubicin between different populations. No significant financial relationships to disclose.
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