scholarly journals Cho/Cr ratio at MR spectroscopy as a biomarker for cellular proliferation activity and prognosis in glioma: correlation with the expression of minichromosome maintenance protein 2

2018 ◽  
Vol 60 (1) ◽  
pp. 106-112 ◽  
Author(s):  
Wenjing Gao ◽  
Xiao Wang ◽  
Fuyan Li ◽  
Wenqi Shi ◽  
Hongxia Li ◽  
...  
Keyword(s):  
Mr Spectroscopy ◽  
Proliferative Activity ◽  
Cellular Proliferation ◽  
Prognostic Markers ◽  
Cox Regression ◽  
Pearson Correlation ◽  
Minichromosome Maintenance ◽  
Proliferation Activity ◽  
Minichromosome Maintenance Protein ◽  
Cell Proliferative Activity

Background Magnetic resonance (MR) spectroscopy (1H-MRS) has been demonstrated to be useful in grading glioma, but the utility in assessing cellular proliferation activity and prognosis correlated with the expression of minichromosome maintenance protein 2 (MCM2) has not been reported. Purpose To explore the correlation between proton MR spectroscopy parameters (including choline [Cho]/creatine [Cr], N-acetyl aspartate [NAA]/Cr, and Cho/NAA ratios) and the expression of MCM2 and to further evaluate whether 1H-MRS can predict cell proliferative activity and provide prognostic information in high-grade gliomas (HGGs). Material and Methods Forty-three patients with histopathologically confirmed gliomas were involved in this study. All patients underwent 1H-MRS examination before surgery. Proliferative activity of gliomas was evaluated by MCM2 labeling index (LI). Pearson correlation analysis and empiric receiver operating characteristic (ROC) curves were performed. The Kaplan–Meier method and Cox regression were used for survival analysis. Results Significant correlation was observed between the Cho/Cr ratio and MCM2 LI ( r = 0.522, P < 0.01); however, there was no correlation between MCM2 LI and the Cho/NAA or NAA/Cr ratios ( r = 0.295, P = 0.55 and r = −0.042, P = 0.788, respectively). According to ROC analysis, MCM2 LI of 50% and Cho/Cr ratio of 2.68 represented the optimized cut-off values, respectively, to distinguish longer or shorter survival than 15 months in HGGs patients. Multivariate analysis revealed that both the Cho/Cr ratio and MCM2 expression were independent prognostic markers. Conclusion Cho/Cr ratio has a potential in predicting the expression of MCM2 and can evaluate cell proliferative activity noninvasively. Both the Cho/Cr ratio and MCM2 expression are independent prognostic markers in patients with HGGs.

scholarly journals Bi-allelic MCM10 variants associated with immune dysfunction and cardiomyopathy cause telomere shortening

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ryan M. Baxley ◽  
Wendy Leung ◽  
Megan M. Schmit ◽  
Jacob Peter Matson ◽  
Lulu Yin ◽  
...  
Keyword(s):  
Immune Cell ◽  
Nk Cell ◽  
Restrictive Cardiomyopathy ◽  
Telomerase Activity ◽  
Compound Heterozygous ◽  
Minichromosome Maintenance ◽  
Telomere Shortening ◽  
Clinical Phenotypes ◽  
Eukaryotic Dna ◽  
Minichromosome Maintenance Protein

AbstractMinichromosome maintenance protein 10 (MCM10) is essential for eukaryotic DNA replication. Here, we describe compound heterozygous MCM10 variants in patients with distinctive, but overlapping, clinical phenotypes: natural killer (NK) cell deficiency (NKD) and restrictive cardiomyopathy (RCM) with hypoplasia of the spleen and thymus. To understand the mechanism of MCM10-associated disease, we modeled these variants in human cell lines. MCM10 deficiency causes chronic replication stress that reduces cell viability due to increased genomic instability and telomere erosion. Our data suggest that loss of MCM10 function constrains telomerase activity by accumulating abnormal replication fork structures enriched with single-stranded DNA. Terminally-arrested replication forks in MCM10-deficient cells require endonucleolytic processing by MUS81, as MCM10:MUS81 double mutants display decreased viability and accelerated telomere shortening. We propose that these bi-allelic variants in MCM10 predispose specific cardiac and immune cell lineages to prematurely arrest during differentiation, causing the clinical phenotypes observed in both NKD and RCM patients.

scholarly journals Synergistic Roles of Curcumin in Sensitising the Cisplatin Effect on a Cancer Stem Cell-Like Population Derived from Non-Small Cell Lung Cancer Cell Lines

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1056 ◽  
Author(s):  
Nazilah Abdul Satar ◽  
Mohd Nazri Ismail ◽  
Badrul Hisham Yahaya
Keyword(s):  
Lung Cancer ◽  
Stem Cell ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cellular Proliferation ◽  
Combined Treatment ◽  
Small Cell ◽  
Cytotoxic Agents ◽  
Small Cell Lung ◽  
Proliferation Activity

Cancer stem cells (CSCs) represent a small subpopulation within a tumour. These cells possess stem cell-like properties but also initiate resistance to cytotoxic agents, which contributes to cancer relapse. Natural compounds such as curcumin that contain high amounts of polyphenols can have a chemosensitivity effect that sensitises CSCs to cytotoxic agents such as cisplatin. This study was designed to investigate the efficacy of curcumin as a chemo-sensitiser in CSCs subpopulation of non-small cell lung cancer (NSCLC) using the lung cancer adenocarcinoma human alveolar basal epithelial cells A549 and H2170. The ability of curcumin to sensitise lung CSCs to cisplatin was determined by evaluating stemness characteristics, including proliferation activity, colony formation, and spheroid formation of cells treated with curcumin alone, cisplatin alone, or the combination of both at 24, 48, and 72 h. The mRNA level of genes involved in stemness was analysed using quantitative real-time polymerase chain reaction. Liquid chromatography-mass spectrometry was used to evaluate the effect of curcumin on the CSC niche. A combined treatment of A549 subpopulations with curcumin reduced cellular proliferation activity at all time points. Curcumin significantly (p < 0.001) suppressed colonies formation by 50% and shrank the spheroids in CSC subpopulations, indicating inhibition of their self-renewal capability. This effect also was manifested by the down-regulation of SOX2, NANOG, and KLF4. Curcumin also regulated the niche of CSCs by inhibiting chemoresistance proteins, aldehyde dehydrogenase, metastasis, angiogenesis, and proliferation of cancer-related proteins. These results show the potential of using curcumin as a therapeutic approach for targeting CSC subpopulations in non-small cell lung cancer.

scholarly journals Bioprospecting of Sechium spp. varieties for the selection of characters with pharmacological activity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
María Isabel Iñiguez-Luna ◽  
Jorge Cadena-Iñiguez ◽  
Ramón Marcos Soto-Hernández ◽  
Francisco Javier Morales-Flores ◽  
Moisés Cortes-Cruz ◽  
...  
Keyword(s):  
Cell Lines ◽  
Proliferative Activity ◽  
Meta Analysis ◽  
Pearson Correlation ◽  
Statistical Significance ◽  
Economic Value ◽  
Principal Component ◽  
Malignant Cell ◽  
Length Polymorphisms ◽  
Relevant Variables

AbstractBioprospecting identifies new sources of compounds with actual or potential economic value that come from biodiversity. An analysis was performed regarding bioprospecting purposes in ten genotypes of Sechium spp., through a meta-analysis of 20 information sources considering different variables: five morphological, 19 biochemical, anti-proliferative activity of extracts on five malignant cell lines, and 188 polymorphic bands of amplified fragment length polymorphisms, were used in order to identify the most relevant variables for the design of genetic interbreeding. Significant relationships between morphological and biochemical characters and anti-proliferative activity in cell lines were obtained, with five principal components for principal component analysis (SAS/ETS); variables were identified with a statistical significance (< 0.7 and Pearson values ≥ 0.7), with 80.81% of the accumulation of genetic variation and 110 genetic bands. Thirty-nine (39) variables were recovered using NTSYSpc software where 30 showed a Pearson correlation (> 0.5) and nine variables (< 0.05), Finally, using a cladistics analysis approach highlighted 65 genetic bands, in addition to color of the fruit, presence of thorns, bitter flavor, piriform and oblong shape, and also content of chlorophylls a and b, presence of cucurbitacins, and the IC50 effect of chayote extracts on the four cell lines.

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