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1.
Warwick B. Dunn David I. Broadhurst Arthur Edison Claude Guillou Mark R. Viant Daniel W. Bearden Richard D. Beger 《Metabolomics : Official journal of the Metabolomic Society》2017,13(5):50
Introduction
The Metabolomics Society Data Quality Task Group (DQTG) developed a questionnaire regarding quality assurance (QA) and quality control (QC) to provide baseline information about current QA and QC practices applied in the international metabolomics community.Objectives
The DQTG has a long-term goal of promoting robust QA and QC in the metabolomics community through increased awareness via communication, outreach and education, and through the promotion of best working practices. An assessment of current QA and QC practices will serve as a foundation for future activities and development of appropriate guidelines.Method
QA was defined as the set of procedures that are performed in advance of analysis of samples and that are used to improve data quality. QC was defined as the set of activities that a laboratory does during or immediately after analysis that are applied to demonstrate the quality of project data. A questionnaire was developed that included 70 questions covering demographic information, QA approaches and QC approaches and allowed all respondents to answer a subset or all of the questions.Result
The DQTG questionnaire received 97 individual responses from 84 institutions in all fields of metabolomics covering NMR, LC-MS, GC-MS, and other analytical technologies.Conclusion
There was a vast range of responses concerning the use of QA and QC approaches that indicated the limited availability of suitable training, lack of Standard Operating Procedures (SOPs) to review and make decisions on quality, and limited use of standard reference materials (SRMs) as QC materials. The DQTG QA/QC questionnaire has for the first time demonstrated that QA and QC usage is not uniform across metabolomics laboratories. Here we present recommendations on how to address the issues concerning QA and QC measurements and reporting in metabolomics.2.
Rajesh Thiyagarajan Arunai Nambiraj Sujit Nath Sinha Girigesh Yadav Ashok Kumar Vikraman Subramani Kothandaraman 《Reports of Practical Oncology and Radiotherapy》2016,21(1):50-56
Aim
The aim of this study is to evaluate performance of ArcCHECK diode array detector for the volumetric modulated arc therapy (VMAT) patient specific quality assurance (QA). VMAT patient specific QA results were correlated with ion chamber measurement. Dose response of the ArcCHECK detector was studied.Background
VMAT delivery technique improves the dose distribution. It is complex in nature and requires proper QA before its clinical implementation. ArcCHECK is a novel three dimensional dosimetry system.Materials and methods
Twelve retrospective VMAT plans were calculated on ArcCHECK phantom. Point dose and dose map were measured simultaneously with ion chamber (IC-15) and ArcCHECK diode array detector, respectively. These measurements were compared with their respective TPS calculated values.Results
The ion chamber measurements are in good agreement with TPS calculated doses. Mean difference between them is 0.50% with standard deviation of 0.51%. Concordance correlation coefficient (CCC) obtained for ion chamber measurements is 0.9996. These results demonstrate a strong correlation between the absolute dose predicted by our TPS and the measured dose. The CCC between ArcCHECK doses and TPS predictions on the CAX was found to be 0.9978. In gamma analysis of dose map, the mean passing rate was 98.53% for 3% dose difference and 3 mm distance to agreement.Conclusions
The VMAT patient specific QA with an ion chamber and ArcCHECK phantom are consistent with the TPS calculated dose. Statistically good agreement was observed between ArcCHECK measured and TPS calculated. Hence, it can be used for routine VMAT QA. 相似文献3.
David Broadhurst Royston Goodacre Stacey N. Reinke Julia Kuligowski Ian D. Wilson Matthew R. Lewis Warwick B. Dunn 《Metabolomics : Official journal of the Metabolomic Society》2018,14(6):72
Background
Quality assurance (QA) and quality control (QC) are two quality management processes that are integral to the success of metabolomics including their application for the acquisition of high quality data in any high-throughput analytical chemistry laboratory. QA defines all the planned and systematic activities implemented before samples are collected, to provide confidence that a subsequent analytical process will fulfil predetermined requirements for quality. QC can be defined as the operational techniques and activities used to measure and report these quality requirements after data acquisition.Aim of review
This tutorial review will guide the reader through the use of system suitability and QC samples, why these samples should be applied and how the quality of data can be reported.Key scientific concepts of review
System suitability samples are applied to assess the operation and lack of contamination of the analytical platform prior to sample analysis. Isotopically-labelled internal standards are applied to assess system stability for each sample analysed. Pooled QC samples are applied to condition the analytical platform, perform intra-study reproducibility measurements (QC) and to correct mathematically for systematic errors. Standard reference materials and long-term reference QC samples are applied for inter-study and inter-laboratory assessment of data.4.
Shahla Ebrahimi Moghadam Shahrokh Nasseri Seyedeh Somayeh Seyedi Hamid Gholamhosseinian Mehdi Momennezhad 《Reports of Practical Oncology and Radiotherapy》2018,23(5):369-377
Aim
Evaluation of application of EPID for rapid QC testing of linear accelerator.Background
Quality control of a linear accelerator device is a time and energy intensive process. In this study, attempts have been made to perform the linear accelerator quality control using electronic portal imaging device (EPID), which is mounted on most accelerators.Materials and methods
First, quality control and dosimetry parameters of the device were determined and measured based on standard protocols to ensure full calibration of the accelerator. Then, various features of EPID including spatial resolution and contrast resolution, the effect of buildup region, dose response and image uniformity were evaluated. In the next step, consistent with the parameters of linear accelerator quality control including field size, field flatness and symmetry, the light field coincidence with X-ray field, mechanical stability and multileaf collimator position accuracy test, the output images of device were obtained.After feeding images to the MATLAB software, their pixel content was analyzed. All measurements of the three photon beams were repeated three times.Results
The EPID image had a desirable resolution, contrast and uniformity and displayed high sensitivity to dose changes with linear dose response. Seven qualitative parameters of the linear accelerator were then controlled by EPID.Conclusions
The results of the linear accelerator quality control using the EPID were consistent with practice. Quality control using the EPID was more convenient and faster than conventional methods. 相似文献5.
JC. Brisset F. Gazeau C. Corot N. Nighoghossian Y. Berthezène E. Canet-Soulas M. Wiart 《IRBM》2018,39(2):93-102
Background
Inflammation is a share process in atherosclerosis and stroke and is thought to be a key player in the evolution of these diseases. Ten years ago, inflammation imaging with magnetic resonance imaging (MRI) was considered very promising for both pre-clinical and clinical studies of atherosclerosis and stroke.Contribution
We report here contributions to the field of inflammation imaging with USPIO-enhanced MRI. The goal was to investigate the life cycle of USPIOs in the body, and how the MRI signal has been impacted during their bio-interactions and bioprocessing. Those mechanisms were applied to pre-clinical longitudinal studies of inflammation in atherosclerosis and at the acute stage of ischemic stroke thus allowing the monitoring of treatment effects.Conclusion
This review presents the contribution of the collaborative research project under the “TecSan” grant from the French Research Agency (ANR) as well as pre-clinical and clinical perspectives of USPIO's inflammation MRI in atherosclerosis and stroke. 相似文献6.
7.
Lei Li Ryan Z.L. Lim Lawrence S.U. Lee Nicholas S.Y. Chew 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(8):1790-1800
Background
HIV infection and/or the direct pathogenic effects of circulating HIV proteins impairs the physiological function of mesenchymal stem cells (MSCs), and contribute to the pathogenesis of age-related clinical comorbidities in people living with HIV. The SDF-1/CXCR4 pathway is vital for modulating MSC proliferation, migration and differentiation. HIV glycoprotein gp120 inhibits SDF-1 induced chemotaxis by downregulating the expression and function of CXCR4 in monocytes, B and T cells. The influence of gp120 on CXCR4 expression and migration in MSCs is unknown.Methods
We investigated CXCR4 expression and SDF-1/CXCR4-mediated MSC migration in response to gp120, and its effect on downstream signaling pathways: focal adhesion kinase (FAK)/Paxillin and extracellular signal-regulated kinase (ERK).Results
Gp120 upregulated MSC CXCR4 expression. This potentiated the effects of SDF-1 in inducing chemotaxis; FAK/Paxillin and ERK pathways were over-activated, thereby facilitating actin stress fiber reorganization. CXCR4 blockage or depletion abrogated the observed effects.Conclusion
Gp120 from both T- and M- tropic HIV strains upregulated CXCR4 expression in MSCs, resulting in enhanced MSC chemotaxis in response to SDF-1.General significance
HIV infection and its proteins are known to disrupt physiological differentiation of MSC; increased gp120-driven migration amplifies the total MSC population destined for ineffective and inappropriate differentiation, thus contributing to the pathogenesis of HIV-related comorbidities. Additionally, given that MSCs are permissive to HIV infection, initial cellular priming by gp120 results in increased expression of CXCR4 and could lead to co-receptor switching and cell tropism changes in chronic HIV infection and may have implications against CCR5-knockout based HIV cure strategies. 相似文献8.
Nithya Kanakavelu E. James Jebaseelan Samuel 《Reports of Practical Oncology and Radiotherapy》2015,20(3):188-197
Background and aim
The clinical use of imaging system in image guided radiotherapy (IGRT) necessitates performing periodic quality assurance of the system to be confident in applying corrections for patient set-up errors. We aim to develop and implement a quality assurance (QA) programme for megavoltage (MV) based image guidance system and assess its long term performance for a period of 3 years.Materials and methods
Periodic QA tests were performed for the MV planar and cone beam computed tomography (CBCT) imaging system to assess the system safety, mechanical and geometrical accuracy, image quality and dose. The tests were performed using the equipment supplied by the manufacturer along with the image guidance system and using simple methods developed in-house. The test results were compared with expected or baseline values established during commissioning.Results
The safety system was found to be functional. The results of mechanical and geometrical tests were in good agreement with the expected results. The system mechanical positioning was stable and reproducible within ±2 mm accuracy. The image quality and the imaging dose of the planar and CBCT imaging were found to agree with the baseline values and the manufacturer specifications.Discussion
Throughout the three-year period, all the QA tests were within the specification. The mechanical and geometrical tests are most crucial as they directly affect the patient positioning accuracy.Conclusion
We conclude that the MV image guidance system is efficient to perform IGRT and insist to perform periodic QA tests and calibration for the system. 相似文献9.
Jason L. Wedding Barry Lai Stefan Vogt Hugh H. Harris 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(11):2393-2404
Background
A variety of selenium compounds have been observed to provide protection against oxidative stress, presumably by mimicking the mechanism of action of the glutathione peroxidases. However, the selenium chemistry that underpins the action of these compounds has not been unequivocally established.Methods
The synchrotron based techniques, X-ray absorption spectroscopy and X-ray fluorescence microscopy were used to examine the cellular speciation and distribution of selenium in SH-SY5Y cells pretreated with one of two diphenyl diselenides, or ebselen, followed by peroxide insult.Results
Bis(2-aminophenyl)diselenide was shown to protect against oxidative stress conditions which mimic ischemic strokes, while its nitro analogue, bis(2-nitrophenyl)diselenide did not. This protective activity was tentatively assigned to the reductive cleavage of bis(2-aminophenyl)diselenide inside human neurocarcinoma cells, SH-SY5Y, while bis(2-nitrophenyl)diselenide remained largely unchanged. The distinct chemistries of the related compounds were traced by the changes in selenium speciation in bulk pellets of treated SH-SY5Y cells detected by X-ray absorption spectroscopy. Further, bis(2-aminophenyl)diselenide, like the known stroke mitigation agent ebselen, was observed by X-ray fluorescence imaging to penetrate into the nucleus of SH-SY5Y cells while bis(2-nitrophenyl)diselenide was observed to be excluded from the nuclear region.Conclusions
The differences in activity were thus attributed to the varied speciation and cellular localisation of the compounds, or their metabolites, as detected by X-ray absorption spectroscopy and X-ray fluorescence microscopy.Significance
The work is significant as it links, for the first time, the protective action of selenium compounds against redox stress with particular chemical speciation using a direct measurement approach. 相似文献10.
Background aims
In vitro engineered adipose tissue is in great demand to treat lost or damaged soft tissue or to screen for new drugs, among other applications. However, today most attempts depend on the use of animal-derived sera. To pave the way for the application of adipose tissue–engineered products in clinical trials or as reliable and robust in vitro test systems, sera should be completely excluded from the production process. In this study, we aimed to develop an in vitro adipose tissue model in the absence of sera and maintain its function long-term.Methods
Human adipose tissue–derived stem cells were expanded and characterized in a xeno- and serum-free environment. Adipogenic differentiation was induced using a completely defined medium. Developed adipocytes were maintained in a completely defined maturation medium for additional 28 days. In addition to cell viability and adherence, adipocyte-specific markers such as perilipin A expression or leptin release were evaluated.Results
The defined differentiation medium enhanced cell adherence and lipid accumulation at a significant level compared with the corresponding negative control. The defined maturation medium also significantly supported cell adherence and functional adipocyte maturation during the long-term culture period.Conclusions
The process described here enables functional adipocyte generation and maintenance without the addition of unknown or animal-derived constituents, achieving an important milestone in the introduction of adipose tissue–engineered products into clinical trials or in vitro screening. 相似文献11.
Y?ld?ray ?zgüven Kadir Yaray Fadime Alkaya Birsen Yücel Serdar Soyuer 《Reports of Practical Oncology and Radiotherapy》2014,19(3):195-205
Aim
The purpose of the present study is to show the application of the IAEA TRS-430 QA procedures of Eclipse™v7.5 TPS for photon energies. In addition, the trends of the deviations found in the conducted tests were determined.Background
In the past, the lack of complete TPS QA procedures led to some serious accidents. So, QA in the radiotherapy treatment planning process is essential for determination of accuracy in the radiotherapy process and avoidance of treatment errors.Materials and methods
The calculations of TPS and measurements of irradiations of the treatment device were compared in the study. As a result, the local dose deviation values (δ1: central beam axis, δ2: penumbra and build up region, δ3: inside field, δ4: outside beam edges, δ50–90: beam fringe, RW50: radiological width) and their confidence limit values (including systematic and random errors) were obtained.Results
The confidence limit values of δ4 were detected to increase with expanding field size. The values of δ1 and δ3 of hard wedge were larger than open fields. The values of δ2 and δ50–90 of the inhomogeneity effect test were larger, especially than other tests of this study. The average deviation was showed to increase with the rise of the wedge angle. The values of δ3 and δ4 of lung irradiation were outside tolerance.Conclusions
The QA of TPS was done and it was found that there were no reservations in its use in patient treatment. The trend of the deviations is shown. 相似文献12.
Background
Interleukin-35 (IL-35) has recently been identified as an immunosuppressive cytokine that has been used as a potential therapy for chronic inflammatory and autoimmune diseases. However, there remains a paucity of data regarding its potential benefits after integration into mesenchymal stem cells (MSCs).Methods
We used a dextran sulfate sodium (DSS)–induced colitis mice model and treated them with IL-35-MSCs, MSCs or saline. The body weight was recorded daily and inflammatory processes were determined. Cytokine secretion by lamina propria lymphocytes (LPLs) and percentage of regulatory T cells (Tregs) were also measured.Results
The data showed that mice in the two treated groups recovered their body weight more rapidly than mice treated with saline in the later stage of colitis. The colon lengths of IL-35-MSC–treated mice were markedly longer than those in the other two groups and the inflammation reduced significantly. Furthermore, the percentage of Foxp3?+?Tregs increased significantly and the level of proinflammatory cytokines produced by LPLs decreased significantly in the IL-35-MSC–treated group.Discussion
The results demonstrate that IL-35-MSCs could ameliorate ulcerative colitis by down-regulating the expression of pro-inflammatory cytokines. 相似文献13.
CONTEXT:
Survivors of the Bhopal gas disaster still suffer from various respiratory ailments. We examined the effects of exposures among a cross-section of current residents suffering from COPD by ISSR-PCR.AIMS:
Molecular screening of the gas-affected population of Bhopal with COPD for microsatellite instability due to exposure of MIC.SETTINGS AND DESIGN:
The isocyanate-exposed population of Bhopal city suffering from chronic obstructive pulmonary disorder.MATERIALS AND METHODS:
Inter-(SSR) analysis was used to characterize microsatellite instability in 52 MIC victims of Bhopal, suffering from COPD using (CA)8RG and (CA)8R[Y-Q] primer.STATISTICAL ANALYSIS USED:
Association analyses were performed using regression analysis.RESULTS:
The study on the MIC-affected population in Bhopal showed weak association between microsatellite instability and age (r = + 0.37); exposure distance from site (r = −0.44); and smoking status(r = + 0.12); while regression analysis of the above parameters displayed supporting evidence.CONCLUSIONS:
The high prevalence of smoking coupled with aging and poor living habits threatens, to further increase COPD incidences among this population, highlighting the need for enhanced screening efforts. 相似文献14.
Ramya Rangarajan 《Reports of Practical Oncology and Radiotherapy》2018,23(1):57-60
Aim
The aim of the study is to evaluate the differences in dosimetry between tandem-ovoid and tandem-ring gynaecologic brachytherapy applicators in image based brachytherapy.Background
Traditionally, tandem ovoid applicators were used to deliver dose to tumor in intracavitary brachytherapy. Tandem-ring, tandem-cylinder and hybrid intracavitary, interstitial applicators are also used nowadays in cervical cancer brachytherapy.Methods and materials
100 CT datasets of cervical cancer patients (stage IB2 – IIIB) receiving HDR application (50 tandem-ovoid and 50 tandem-ring) were studied. Brachytherapy was delivered using a CT-MRI compatible tandem-ovoid (50 patients) and a tandem-ring applicator (50 patients). DVHs were calculated and D2cc was recorded for the bladder and rectum and compared with the corresponding ICRU point doses. The point B dose, the treated volume, high dose volume and the treatment time were recorded and compared for the two applicators.Results
The mean D2cc of the bladder with TR applicator was 6.746 Gy. TO applicator delivered a mean D2cc of 7.160 Gy to the bladder. The mean ICRU bladder points were 5.60 and 5.63 Gy for TR and TO applicator, respectively. The mean D2cc of the rectum was 4.04 Gy and 4.79 Gy for TR and TO applicators, respectively. The corresponding ICRU point doses were 5.10 Gy and 5.66 Gy, respectively.Conclusions
The results indicate that the OAR doses assessed by DVH criteria were higher than ICRU point doses for the bladder with both tandem-ovoid and tandem-ring applicators whereas DVH based dose was lower than ICRU dose for the rectum. The point B dose, the treated volume and high dose volume was found to be slightly higher with the tandem-ovoid applicator. The mean D2cc dose for the bladder and rectum was lower with tandem-ring applicators. The clinical implication of the above dosimetric differences needs to be evaluated further. 相似文献15.
Aristides T. Hatjimihail 《PloS one》2009,4(6)
Background
An open problem in clinical chemistry is the estimation of the optimal sampling time intervals for the application of statistical quality control (QC) procedures that are based on the measurement of control materials. This is a probabilistic risk assessment problem that requires reliability analysis of the analytical system, and the estimation of the risk caused by the measurement error.Methodology/Principal Findings
Assuming that the states of the analytical system are the reliability state, the maintenance state, the critical-failure modes and their combinations, we can define risk functions based on the mean time of the states, their measurement error and the medically acceptable measurement error. Consequently, a residual risk measure rr can be defined for each sampling time interval. The rr depends on the state probability vectors of the analytical system, the state transition probability matrices before and after each application of the QC procedure and the state mean time matrices. As optimal sampling time intervals can be defined those minimizing a QC related cost measure while the rr is acceptable. I developed an algorithm that estimates the rr for any QC sampling time interval of a QC procedure applied to analytical systems with an arbitrary number of critical-failure modes, assuming any failure time and measurement error probability density function for each mode. Furthermore, given the acceptable rr, it can estimate the optimal QC sampling time intervals.Conclusions/Significance
It is possible to rationally estimate the optimal QC sampling time intervals of an analytical system to sustain an acceptable residual risk with the minimum QC related cost. For the optimization the reliability analysis of the analytical system and the risk analysis of the measurement error are needed. 相似文献16.
Yuta Murakami Koichi Takahashi Kyoka Hoshi Hiromi Ito Mayumi Kanno Kiyoshi Saito Kenneth Nollet Yoshiki Yamaguchi Masakazu Miyajima Hajime Arai Yasuhiro Hashimoto Tatsuo Mima 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(8):1835-1842
Background
Spontaneous intracranial hypotension (SIH) is caused by cerebrospinal fluid (CSF) leakage. Definitive diagnosis can be difficult by clinical examinations and imaging studies.Methods
SIH was diagnosed with the following criteria: (i) evidence of CSF leakage by cranial magnetic resonance imaging (MRI) findings of intracranial hypotension and/or low CSF opening pressure; (ii) no recent history of dural puncture. We quantified CSF proteins by ELISA or Western blotting.Results
Comparing with non-SIH patients, SIH patients showed significant increase of brain-derived CSF glycoproteins such as lipocalin-type prostaglandin D synthase (L-PGDS), soluble protein fragments generated from amyloid precursor protein (sAPP) and “brain-type” transferrin (Tf). Serum-derived proteins such as albumin, immunoglobulin G, and serum Tf were also increased. A combination of L-PGDS and brain-type Tf differentiated SIH from non-SIH with sensitivity 94.7% and specificity 72.6%.Conclusion
L-PGDS and brain-type Tf can be biomarkers for diagnosing SIH.General significance
L-PGDS and brain-type Tf biosynthesized in the brain appears to be markers for abnormal metabolism of CSF. 相似文献17.
Afsaneh Sadremomtaz Kamran Mansouri Golnaz Alemzadeh Majid Safa Ahmadreza Esmaeili Rastaghi S. Mohsen Asghari 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(12):2688-2700
Background
Neutralization of vascular endothelial growth factor receptor 1 (VEGFR1) and/or VEGFR2 is a widely used means of inhibiting tumor angiogenesis.Methods
Based on the complex X-ray structures of VEGFA/VEGFR1, VEGFA/VEGFR2, and VEGFB/VEGFR1, a peptide (referred to as VGB) was designed to simultaneously bind to VEGFR1 and VEGFR2, and binding, antiangiogenic and antitumor properties of the peptide was investigated in vitro.Results
VGB bound to both VEGFR1 and VEGFR2 in human umbilical vein endothelial cells (HUVECs) and 4?T1 mammary carcinoma tumor (MCT) cells, and inhibited the proliferation of HUVE, 4?T1 MCT, and U87 glioblastoma cells. Through abrogation of AKT and ERK1/2 phosphorylation, VEGFA-stimulated proliferation, migration, and two- and three-dimensional tube formation in HUVECs were inhibited more potently by VGB than by bevacizumab. In a murine 4?T1 MCT model, VGB strongly inhibited tumor growth without causing weight loss, accompanied by inhibition of AKT and ERK1/2 phosphorylation, a significant decrease in tumor cell proliferation (Ki-67 expression), angiogenesis (CD31 and CD34 expression), an increase in apoptosis index (increased TUNEL staining and p53 expression and decreased Bcl-2 expression), and the suppression of systematic spreading of the tumor (reduced NF-κB and MMP-9 and increased E-cadherin expression).Conclusion
The dual specificity of VGB for VEGFR1 and VEGFR2, through which the PI3K/AKT and MAPK/ERK1/2 signaling pathways can be abrogated and, subsequently, angiogenesis, tumor growth, and metastasis are inhibited.General significance
This study demonstrated that simultaneous blockade of VEGFR1 and VEGFR2 downstream cascades is an effective means for treatment of various angiogenic disorders, especially cancer. 相似文献18.
Ryota Iino Tatsuya Iida Akihiko Nakamura Ei-ichiro Saita Huijuan You Yasushi Sako 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(2):241-252
Background
Biological molecular machines support various activities and behaviors of cells, such as energy production, signal transduction, growth, differentiation, and migration.Scope of review
We provide an overview of single-molecule imaging methods involving both small and large probes used to monitor the dynamic motions of molecular machines in vitro (purified proteins) and in living cells, and single-molecule manipulation methods used to measure the forces, mechanical properties and responses of biomolecules. We also introduce several examples of single-molecule analysis, focusing primarily on motor proteins and signal transduction systems.Major conclusions
Single-molecule analysis is a powerful approach to unveil the operational mechanisms both of individual molecular machines and of systems consisting of many molecular machines.General significance
Quantitative, high-resolution single-molecule analyses of biomolecular systems at the various hierarchies of life will help to answer our fundamental question: “What is life?” This article is part of a Special Issue entitled "Biophysical Exploration of Dynamical Ordering of Biomolecular Systems" edited by Dr. Koichi Kato. 相似文献19.
Lin Wang Ziru Yu Shuyue Ren Junke Song Jinhua Wang Guanhua Du 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(10):2281-2292
Background
Metabolic reprogramming and hypoxia contribute to the resistance of conventional chemotherapeutic drugs in kinds of cancers. In this study, we investigated the effect of dihydrotanshinone I (DHTS) on reversing dysregulated metabolism of glucose and fatty acid in colon cancer and elucidated its mechanism of action.Methods
Cell viability was determined by MTT assay. Oxidative phosphorylation, glycolysis, and mitochondrial fuel oxidation were assessed by Mito stress test, glycolysis stress test, and mito fuel flex test, respectively. Anti-cancer activity of DHTS in vivo was evaluated in Colon cancer xenograft. Hexokinase activity and free fatty acid (FFA) content were assessed using respective Commercial kits. Gene expression patterns were determined by performing DNA microarray analysis and real-time PCR. Protein expression was assessed using immunoblotting and immunohistochemistry.Results
DHTS showed similar cytotoxicity against colon cancer cells under hypoxia and normoxia. DHTS decreased the efficiency of glucose and FA as mitochondrial fuels in HCT116 cells, which efficiently reversed by VO-OHpic trihydrate. DHTS reduced hexokinase activity and free fatty acid (FFA) content in tumor tissue of xenograft model of colon cancer. Gene expression patterns in metabolic pathways were dramatically differential between model and treatment group. Increases in PTEN and a substantial decrease in the expression of SIRT3, HIF1α, p-AKT, HKII, p-MTOR, RHEB, and p-ACC were detected.Conclusions
DHTS reversed metabolic reprogramming in colon cancer through PTEN/AKT/HIF1α-mediated signal pathway.General significance
The study is the first to report the reverse of metabolic reprogramming by DHTS in colon cancer. Meantime, SIRT3/PTEN/AKT/HIF1α mediated signal pathway plays a critical role during this process. 相似文献20.
Andreas Stylianou Vasiliki Gkretsi Triantafyllos Stylianopoulos 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(7):1537-1546