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1.
Jie Yang Jianhua Cheng Bo Sun Haijing Li Shengming Wu Fangting Dong Xianzhong Yan 《Metabolomics : Official journal of the Metabolomic Society》2018,14(4):40
Introduction
Hypoxia commonly occurs in cancers and is highly related with the occurrence, development and metastasis of cancer. Treatment of triple negative breast cancer remains challenge. Knowledge about the metabolic status of triple negative breast cancer cell lines in hypoxia is valuable for the understanding of molecular mechanisms of this tumor subtype to develop effective therapeutics.Objectives
Comprehensively characterize the metabolic profiles of triple negative breast cancer cell line MDA-MB-231 in normoxia and hypoxia and the pathways involved in metabolic changes in hypoxia.Methods
Differences in metabolic profiles affected pathways of MDA-MB-231 cells in normoxia and hypoxia were characterized using GC–MS based untargeted and stable isotope assisted metabolomic techniques.Results
Thirty-three metabolites were significantly changed in hypoxia and nine pathways were involved. Hypoxia increased glycolysis, inhibited TCA cycle, pentose phosphate pathway and pyruvate carboxylation, while increased glutaminolysis in MDA-MB-231 cells.Conclusion
The current results provide metabolic differences of MDA-MB-231 cells in normoxia and hypoxia conditions as well as the involved metabolic pathways, demonstrating the power of combined use of untargeted and stable isotope-assisted metabolomic methods in comprehensive metabolomic analysis.2.
Mohammad Reza Abbaszadegan Anali Riahi Mohammad Mahdi Forghanifard Meysam Moghbeli 《Cellular & molecular biology letters》2018,23(1):42
Background
Esophageal squamous cell carcinoma (ESCC) is the most common histological type of esophageal cancer, with a poor prognosis. Deregulation of WNT and NOTCH signaling pathways is important in ESCC progression, which can be due to either malfunction of their components or crosstalk with other pathways. Therefore, identification of new crosstalk between such pathways may be effective to introduce new strategies for targeted therapy of cancer. A correlation study was performed to assess the probable interaction between growth factor receptors and WNT/NOTCH pathways via the epidermal growth factor receptor (EGFR) and Musashi1 (MSI1), respectively.Methods
Levels of MSI1/EGFR mRNA expression in tumor tissues from 48 ESCC patients were compared to their corresponding normal tissues using real-time polymerase chain reaction.Results
There was a significant correlation between EGFR and MSI1 expression (p?=?0.05). Moreover, there was a significant correlation between EGFR/MSI1 expression and grade of tumor differentiation (p?=?0.02).Conclusion
This study confirms a direct correlation between MSI1 and EGFR and may support the important role of MSI1 in activation of EGFR through NOTCH/WNT pathways in ESCC.3.
Margaux Luck Neila Talbi Laurent Gouya Cédric Caradeuc Hervé Puy Gildas Bertho Nicolas Pallet 《Metabolomics : Official journal of the Metabolomic Society》2018,14(1):10
Introduction
Metabolomic profiling combines Nuclear Magnetic Resonance spectroscopy with supervised statistical analysis that might allow to better understanding the mechanisms of a disease.Objectives
In this study, the urinary metabolic profiling of individuals with porphyrias was performed to predict different types of disease, and to propose new pathophysiological hypotheses.Methods
Urine 1H-NMR spectra of 73 patients with asymptomatic acute intermittent porphyria (aAIP) and familial or sporadic porphyria cutanea tarda (f/sPCT) were compared using a supervised rule-mining algorithm. NMR spectrum buckets bins, corresponding to rules, were extracted and a logistic regression was trained.Results
Our rule-mining algorithm generated results were consistent with those obtained using partial least square discriminant analysis (PLS-DA) and the predictive performance of the model was significant. Buckets that were identified by the algorithm corresponded to metabolites involved in glycolysis and energy-conversion pathways, notably acetate, citrate, and pyruvate, which were found in higher concentrations in the urines of aAIP compared with PCT patients. Metabolic profiling did not discriminate sPCT from fPCT patients.Conclusion
These results suggest that metabolic reprogramming occurs in aAIP individuals, even in the absence of overt symptoms, and supports the relationship that occur between heme synthesis and mitochondrial energetic metabolism.4.
Antonella Del-Corso Mario Cappiello Roberta Moschini Francesco Balestri Umberto Mura 《Metabolomics : Official journal of the Metabolomic Society》2018,14(1):2
Introduction
While the evolutionary adaptation of enzymes to their own substrates is a well assessed and rationalized field, how molecules have been originally selected in order to initiate and assemble convenient metabolic pathways is a fascinating, but still debated argument.Objectives
Aim of the present study is to give a rationale for the preferential selection of specific molecules to generate metabolic pathways.Methods
The comparison of structural features of molecules, through an inductive methodological approach, offer a reading key to cautiously propose a determining factor for their metabolic recruitment.Results
Starting with some commonplaces occurring in the structural representation of relevant carbohydrates, such as glucose, fructose and ribose, arguments are presented in associating stable structural determinants of these molecules and their peculiar occurrence in metabolic pathways.Conclusions
Among other possible factors, the reliability of the structural asset of a molecule may be relevant or its selection among structurally and, a priori, functionally similar molecules.5.
Andrew Brandmaier Sheng-Qi Hou Sandra Demaria Silvia C. Formenti Wen H. Shen 《生物学前沿》2017,12(3):163-174
Background
PTEN is well known to function as a tumor suppressor that antagonizes oncogenic signaling and maintains genomic stability. The PTEN gene is frequently deleted or mutated in human cancers and the wide cancer spectrum associated with PTEN deficiency has been recapitulated in a variety of mouse models of Pten deletion or mutation. Pten mutations are highly penetrant in causing various types of spontaneous tumors that often exhibit resistance to anticancer therapies including immunotherapy. Recent studies demonstrate that PTEN also regulates immune functionality.Objective
To understand the multifaceted functions of PTEN as both a tumor suppressor and an immune regulator.Methods
This review will summarize the emerging knowledge of PTEN function in cancer immunoediting. In addition, the mechanisms underlying functional integration of various PTEN pathways in regulating cancer evolution and tumor immunity will be highlighted.Results
Recent preclinical and clinical studies revealed the essential role of PTEN in maintaining immune homeostasis, which significantly expands the repertoire of PTEN functions. Mechanistically, aberrant PTEN signaling alters the interplay between the immune system and tumors, leading to immunosuppression and tumor escape.Conclusion
Rational design of personalized anti-cancer treatment requires mechanistic understanding of diverse PTEN signaling pathways in modulation of the crosstalk between tumor and immune cells.6.
Ferran Casbas Pinto Srinivarao Ravipati David A. Barrett T. Charles Hodgman 《Metabolomics : Official journal of the Metabolomic Society》2017,13(7):81
Introduction
It is difficult to elucidate the metabolic and regulatory factors causing lipidome perturbations.Objectives
This work simplifies this process.Methods
A method has been developed to query an online holistic lipid metabolic network (of 7923 metabolites) to extract the pathways that connect the input list of lipids.Results
The output enables pathway visualisation and the querying of other databases to identify potential regulators. When used to a study a plasma lipidome dataset of polycystic ovary syndrome, 14 enzymes were identified, of which 3 are linked to ELAVL1—an mRNA stabiliser.Conclusion
This method provides a simplified approach to identifying potential regulators causing lipid-profile perturbations.7.
8.
Background
Maximum parsimony phylogenetic tree reconciliation is an important technique for reconstructing the evolutionary histories of hosts and parasites, genes and species, and other interdependent pairs. Since the problem of finding temporally feasible maximum parsimony reconciliations is NP-complete, current methods use either exact algorithms with exponential worst-case running time or heuristics that do not guarantee optimal solutions.Results
We offer an efficient new approach that begins with a potentially infeasible maximum parsimony reconciliation and iteratively “repairs” it until it becomes temporally feasible.Conclusions
In a non-trivial number of cases, this approach finds solutions that are better than those found by the widely-used Jane heuristic.9.
Amir Abdoli 《生物学前沿》2017,12(6):387-391
Background
Inflammatory conditions are involved in the pathophysiology of cancer. Recent findings have revealed that excessive salt and fat intake is involved in the development of severe inflammatory reactions.Methods
literature search was performed on various online databases (PubMed, Scopus, and Google Scholar) regarding the roles of high salt and fat intake in the induction of inflammatory reactions and their roles in the etiopathogenesis of cancer.Results
The results indicate that high salt and fat intake can induce severe inflammatory conditions. However, various inflammatory conditions have been strongly linked to the development of cancer. Hence, high salt and fat intake might be involved in the pathogenesis of cancer progression via putative mechanisms related to inflammatory reactions.Conclusion
Reducing salt and fat intake may decrease the risk of cancer.10.
Objectives
To characterize biomarkers that underlie osteosarcoma (OS) metastasis based on an ego-network.Results
From the microarray data, we obtained 13,326 genes. By combining PPI data and microarray data, 10,520 shared genes were found and constructed into ego-networks. 17 significant ego-networks were identified with p < 0.05. In the pathway enrichment analysis, seven ego-networks were identified with the most significant pathway.Conclusions
These significant ego-modules were potential biomarkers that reveal the potential mechanisms in OS metastasis, which may contribute to understanding cancer prognoses and providing new perspectives in the treatment of cancer.11.
Hye-Jeong Song Eun-Suk Yang Jong-Dae Kim Chan-Young Park Min-Sun Kyung Yu-Seop Kim 《Biomedical engineering online》2018,17(2):152
Background
Screening test using CA-125 is the most common test for detecting ovarian cancer. However, the level of CA-125 is diverse by variable condition other than ovarian cancer. It has led to misdiagnosis of ovarian cancer.Methods
In this paper, we explore the 16 serum biomarker for finding alternative biomarker combination to reduce misdiagnosis. For experiment, we use the serum samples that contain 101 cancer and 92 healthy samples. We perform two major tasks: Marker selection and Classification. For optimal marker selection, we use genetic algorithm, random forest, T-test and logistic regression. For classification, we compare linear discriminative analysis, K-nearest neighbor and logistic regression.Results
The final results show that the logistic regression gives high performance for both tasks, and HE4-ELISA, PDGF-AA, Prolactin, TTR is the best biomarker combination for detecting ovarian cancer.Conclusions
We find the combination which contains TTR and Prolactin gives high performance for cancer detection. Early detection of ovarian cancer can reduce high mortality rates. Finding a combination of multiple biomarkers for diagnostic tests with high sensitivity and specificity is very important.12.
Background
A protein structure can be determined by solving a so-called distance geometry problem whenever a set of inter-atomic distances is available and sufficient. However, the problem is intractable in general and has proved to be a NP hard problem. An updated geometric build-up algorithm (UGB) has been developed recently that controls numerical errors and is efficient in protein structure determination for cases where only sparse exact distance data is available. In this paper, the UGB method has been improved and revised with aims at solving distance geometry problems more efficiently and effectively.Methods
An efficient algorithm (called the revised updated geometric build-up algorithm (RUGB)) to build up a protein structure from atomic distance data is presented and provides an effective way of determining a protein structure with sparse exact distance data. In the algorithm, the condition to determine an unpositioned atom iteratively is relaxed (when compared with the UGB algorithm) and data structure techniques are used to make the algorithm more efficient and effective. The algorithm is tested on a set of proteins selected randomly from the Protein Structure Database-PDB.Results
We test a set of proteins selected randomly from the Protein Structure Database-PDB. We show that the numerical errors produced by the new RUGB algorithm are smaller when compared with the errors of the UGB algorithm and that the novel RUGB algorithm has a significantly smaller runtime than the UGB algorithm.Conclusions
The RUGB algorithm relaxes the condition for updating and incorporates the data structure for accessing neighbours of an atom. The revisions result in an improvement over the UGB algorithm in two important areas: a reduction on the overall runtime and decrease of the numeric error.14.
Samantha M. Carlisle Patrick J. Trainor Xinmin Yin Mark A. Doll Marcus W. Stepp J. Christopher States Xiang Zhang David W. Hein 《Metabolomics : Official journal of the Metabolomic Society》2016,12(7):111
Introduction
Human arylamine N-acetyltransferase 1 (NAT1) is a phase II xenobiotic metabolizing enzyme found in almost all tissues. Expression of NAT1 is elevated in several cancers including breast cancer. However, the exact mechanism by which NAT1 expression affects cancer risk and progression remains unclear.Objective
This study explored polar metabolome differences between MDA-MB-231 breast cancer cells expressing varying levels of NAT1 activity using an untargeted approach.Methods
Three MDA-MB-231 breast adenocarcinoma cell lines that stably express wild-type, increased, and decreased levels of human NAT1 were investigated for differences in polar metabolic profile using a comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-TOF MS) system.Results
Increased levels of human NAT1 in the transformed cell lines resulted in a statistically significant decreased abundance of the metabolite palmitoleic acid (q = 0.0006), when compared to normal and decreased levels of human NAT1. The fatty acid synthesis pathway utilizes acetyl coenzyme A (acetyl-CoA) in the first two reactions of the pathway and eventually leads to the synthesis of palmitoleic acid.Conclusion
These data suggest a link between increased levels of NAT1 activity and decreased flux of acetyl-CoA through this portion of the fatty acid synthesis pathway.15.
Gunjal Garg Ali Yilmaz Praveen Kumar Onur Turkoglu David G. Mutch Matthew A. Powell Barry Rosen Ray O. Bahado-Singh Stewart F. Graham 《Metabolomics : Official journal of the Metabolomic Society》2018,14(12):154
Introduction
Epithelial ovarian cancer (EOC) remains the leading cause of death from gynecologic malignancies and has an alarming global fatality rate. Besides the differences in underlying pathogenesis, distinguishing between high grade (HG) and low grade (LG) EOC is imperative for the prediction of disease progression and responsiveness to chemotherapy.Objectives
The aim of this study was to investigate, the tissue metabolome associated with HG and LG serous epithelial ovarian cancer.Methods
A combination of one dimensional proton nuclear magnetic resonance (1D H NMR) spectroscopy and targeted mass spectrometry (MS) was employed to profile the tissue metabolome of HG, LG serous EOCs, and controls.Results
Using partial least squares-discriminant analysis, we observed significant separation between all groups (p?<?0.05) following cross validation. We identified which metabolites were significantly perturbed in each EOC grade as compared with controls and report the biochemical pathways which were perturbed due to the disease. Among these metabolic pathways, ascorbate and aldarate metabolism was identified, for the first time, as being significantly altered in both LG and HG serous cancers. Further, we have identified potential biomarkers of EOC and generated predictive algorithms with AUC (CI)?=?0.940 and 0.929 for HG and LG, respectively.Conclusion
These previously unreported biochemical changes provide a framework for future metabolomic studies for the development of EOC biomarkers. Finally, pharmacologic targeting of the key metabolic pathways identified herein could lead to novel and effective treatments of EOC.16.
Sami Akbulut Ilker Arer Alper Kocbiyik Mahmut Can Yağmurdur Hamdi Karakayalı Mehmet Haberal 《International Seminars in Surgical Oncology : ISSO》2009,6(1):4
Background
This retrospective study analysed the epidemiological, clinical, and therapeutic profiles of breast cancer in males.Methods
We report our experience at the Hospital of the University of Baskent, where 20 cases of male breast cancer were observed and treated between 1995–2008.Results
Median age at presentation was 66,7 ± 10,9 years. Average follow-up was 63 ± 18,5 months. The main presenting symptom was a mass in 65% of cases (13 patients). Ýnvasive ductal carcinoma was the most frequent pathologic type (70% of cases).Conclusion
Male breast cancer patients have an incidence of prostate cancer higher than would be predicted in the general population. Cause of men have a higher rate of ER positivity the responses with hormonal agents are good.17.
Qing-Yi Lu Xuemei Zhang Jieping Yang Vay-Liang W. Go Wai-Nang Lee 《Metabolomics : Official journal of the Metabolomic Society》2017,13(4):39
Introduction
Loquat leaf extract (LLE) is a mixture rich in terpenoids, and has broad biological activities including the inhibition of cancer cell growth. The exact metabolic mechanism of this growth inhibiting effect is not known.Objectives
We investigated the cellular metabolic effect of LLE, and ursolic acid (UA) on pancreatic cancer cells using a 13C carbon tracing technology.Methods
MIA PaCa-2 cells were cultured in medium containing [1, 2 13C2]-glucose in the presence of either LLE (50 µg/ml), UA (50 µM), or metformin (1 mM). The mass isotopomer distribution of glucose, lactate, ribose, glutamate and palmitate in medium was determined. Based on the mass isotopomer distribution in metabolites we were able to determine individual 13C enrichment (∑M?×?n) and the minimum fraction of new synthesis?(1-M0) in each metabolite. Several flux ratios of energy metabolic pathways were calculated from the mass isotopomer ratios of these metabolites.Results
We found that tumor viability was suppressed by LLE and UA in a dose dependent manner, and the tumor-inhibiting effect was associated with the changes in oxidative/non-oxidative pentose (Ox/Non-ox) and pyruvate dehydrogenase/isocitrate dehydrogenase (PDH/ICDH) flux ratios resulting in decreased new syntheses of ribose and fatty acids.Conclusion
Metabolic homeostasis (balance of fluxes) in cancer cells is maintained through the regulation of metabolic fluxes by oncogenes and tumor-suppressor genes. Treatment of MIA PaCa-2 cells by LLE, UA and metformin likely altered key metabolic flux ratios affecting metabolic homeostasis required for energy and macromolecular production in tumor growth.18.
Tafadzwa Chihanga Sarah M. Hausmann Shuisong Ni Michael A. Kennedy 《Metabolomics : Official journal of the Metabolomic Society》2018,14(3):28
Introduction
Comparative metabolic profiling of different human cancer cell lines can reveal metabolic pathways up-regulated or down-regulated in each cell line, potentially providing insight into distinct metabolism taking place in different types of cancer cells. It is noteworthy, however, that human cell lines available from public repositories are deposited with recommended media for optimal growth, and if cell lines to be compared are cultured on different growth media, this introduces a potentially serious confounding variable in metabolic profiling studies designed to identify intrinsic metabolic pathways active in each cell line.Objectives
The goal of this study was to determine if the culture media used to grow human cell lines had a significant impact on the measured metabolic profiles.Methods
NMR-based metabolic profiles of hydrophilic extracts of three human pancreatic cancer cell lines, AsPC-1, MiaPaCa-2 and Panc-1, were compared after culture on Dulbecco’s Modified Eagle Medium (DMEM) or Roswell Park Memorial Institute (RPMI-1640) medium.Results
Comparisons of the same cell lines cultured on different media revealed that the concentrations of many metabolites depended strongly on the choice of culture media. Analyses of different cell lines grown on the same media revealed insight into their metabolic differences.Conclusion
The choice of culture media can significantly impact metabolic profiles of human cell lines and should be considered an important variable when designing metabolic profiling studies. Also, the metabolic differences of cells cultured on media recommended for optimal growth in comparison to a second growth medium can reveal critical insight into metabolic pathways active in each cell line.19.
Jun Shang Qian Song Zuyi Yang Xiaoyan Sun Meijuan Xue Wenjie Chen Jingcheng Yang Sihua Wang 《Cancer cell international》2018,18(1):218
Background
Programmed cell death 1 (PD-1) functions as an immune checkpoint in the process of anti-tumor immune response. The PD-1 blockade is now becoming a fundamental part in cancer immunotherapy. So it’s essential to elicit the PD-1 related immune process in different types of cancer.Methods
The Cancer Genome Atlas was used to collect the RNA-seq data of 33 cancer types. The microenvironment cell populations-counter was used to analyze the immune cell infiltrates. KEGG and GO analysis were performed to investigate PD-1 associated biological process. Kaplan–Meier survival curves and Cox’s proportional hazards model were performed for prognostic value analysis.Results
We demonstrated that PD-1 expression varied in different cancer types. The uveal melanoma had a low PD-1 expression and poor infiltrated with immune cells. But it showed the strong correlation of PD-1 with the most types of immune cells. The PD-1 demonstrated a robust relationship with other immunomodulators and showed its involvement in critical functions correlated with anti-tumor immune pathways. Survival analysis indicated the PD-1 expression suggested different prognosis in different cancer types.Conclusions
Our investigations promote a better understanding of the PD-1 blockade and provide PD-1 related personized combined immunotherapy for different types of cancer patients.20.
Dingcheng Gao Vivek Mittal Yi Ban Ana Rita Lourenco Shira Yomtoubian Sharrell Lee 《生物学前沿》2018,13(4):277-286