• B vitamins
• Warberg effect
• antioxidants
• cancer
• metabolism
• nutrients

• Humans
• Vitamin B Complex/metabolism
• Vitamin B Complex/therapeutic use
• Neoplasms/prevention & control
• Neoplasms/metabolism
• Disease Progression
• Animals

• 5-flurouracil
• MDA-MB-231 xenograft model
• UHPLC-ESI-QTOF-MS
• doxorubicin
• triple-negative breast cancer
• untargeted metabolomics analysis

• University of Sharjah

• Time-resolved
• autofluorescence
• breast cancer
• flow cytometry
• fluorescence lifetime
• metabolism

• R25 GM061222 NIGMS NIH HHS
• R35 GM152076 NIGMS NIH HHS
• SC1 GM127175 NIGMS NIH HHS
• R01 GM129859 NIGMS NIH HHS
• T32 GM148394 NIGMS NIH HHS

• Breast cancer
• Drug repurposing
• Gene expression
• Microarray
• Oncology

• Humans
• Precision Medicine/methods
• Computational Biology
• Drug Therapy, Combination
• Neoplasms/drug therapy
• Neoplasms/genetics
• Drug Combinations

• Gas Chromatography-Mass Spectrometry/methods
• Metabolomics/methods
• Amino Acids/chemistry
• Carbohydrates/chemistry
• Trimethylsilyl Compounds/chemistry

Breast cancer is the most commonly diagnosed and second leading cause of cancer-related deaths in women in the United States, with hormone receptor positive (HR+) tumors representing more than two-thirds of new cases. Recent evidence has indicated that dysregulation of multiple metabolic programs, which can be driven through nuclear receptor activity, is essential for tumor genesis, progression, therapeutic resistance and metastasis. This study will review the current advances in our understanding of the impact and implication of altered metabolic processes driven by nuclear receptors, including hormone-dependent signaling, on HR+ breast cancer.

Metabolic reprogramming enables cancer cells to adapt to the changing microenvironment in order to maintain metabolic energy and to provide the necessary biological macromolecules required for cell growth and tumor progression. While changes in tumor metabolism have been long recognized as a hallmark of cancer, recent advances have begun to delineate the mechanisms that modulate metabolic pathways and the consequence of altered signaling on tumorigenesis. This is particularly evident in hormone receptor positive (HR+) breast cancers which account for approximately 70% of breast cancer cases. Emerging evidence indicates that HR+ breast tumors are dependent on multiple metabolic processes for tumor progression, metastasis, and therapeutic resistance and that changes in metabolic programs are driven, in part, by a number of key nuclear receptors including hormone-dependent signaling. In this review, we discuss the mechanisms and impact of hormone receptor mediated metabolic reprogramming on HR+ breast cancer genesis and progression as well as the therapeutic implications of these metabolic processes in this disease.

• breast cancer
• endocrine resistance
• estrogen receptor
• luminal
• metabolic reprogramming
• nuclear receptors

Oral squamous cell carcinoma (OSCC) represents 90% of oral malignant neoplasms. The search for specific biomarkers for OSCC is a very active field of research contributing to establishing early diagnostic methods and unraveling underlying pathogenic mechanisms. In this work we investigated the salivary metabolites and the metabolic pathways of OSCC aiming find possible biomarkers. Salivary metabolites samples from 27 OSCC patients and 41 control individuals were compared through a gas chromatography coupled to a mass spectrometer (GC-MS) technique. Our results allowed identification of pathways of the malate-aspartate shuttle, the beta-alanine metabolism, and the Warburg effect. The possible salivary biomarkers were identified using the area under receiver-operating curve (AUC) criterion. Twenty-four metabolites were identified with AUC > 0.8. Using the threshold of AUC = 0.9 we find malic acid, maltose, protocatechuic acid, lactose, 2-ketoadipic, and catechol metabolites expressed. We notice that this is the first report of salivary metabolome in South American oral cancer patients, to the best of our knowledge. Our findings regarding these metabolic changes are important in discovering salivary biomarkers of OSCC patients. However, additional work needs to be performed considering larger populations to validate our results.

• GC-MS
• biomarkers
• mass spectrometry
• metabolites
• metabolomics
• oral cancer
• oral squamous cell carcinoma
• saliva

Both HPV-positive and HPV-negative cervical cancers are associated with aberrant metabolism, although the oncogenic drivers remain elusive. Here we show the assessment of the metabolomic profiles of four distinct cervical cell lines, a normal and three cancer cell lines, one HPV-negative (C33A) and two HPV-positive (SiHa HPV16+, HeLa HPV18+), employing an ultra performance liquid chromatography and a high resolution mass spectrometry. Out of the total 462 metabolites, 248 to 326 exhibited statistically significant differences, while Random Forests analysis identified unique molecules for each cell line. The two HPV+ cell lines exhibited features of Warburg metabolism, consistent with the role of the HPV E6 protein. SiHa and HeLa cells displayed purine salvage pathway activity, while C33A cells revealed synthesis of cytidine, via a novel mechanism. These data document a highly dynamic HPV-specific rewiring of metabolic pathways occurring in cervical cancer. Therefore, this approach can eventually provide novel mechanistic insights into cervical carcinogenesis.

• Plasmodium
• SHMT
• haloacid dehalogenase
• mass spectrometry
• metabolite repair

• Animals
• Electron Transport
• Erythrocytes/parasitology
• Glycine Hydroxymethyltransferase/metabolism
• Hemoglobins/metabolism
• Humans
• Isotope Labeling
• Metabolic Flux Analysis
• Metabolic Networks and Pathways
• Metabolome
• Metabolomics
• Mitochondria/metabolism
• Parasites/growth & development
• Parasites/metabolism
• Phosphoprotein Phosphatases/metabolism
• Plasmodium falciparum/growth & development
• Plasmodium falciparum/metabolism
• Protozoan Proteins/metabolism
• Serine/metabolism
• Terpenes/metabolism
• Trophozoites/metabolism

• R01 AI103280 NIAID NIH HHS
• Department of Health, Australian Government | National Health and Medical Research Council (NHMRC)
• Australian Research Council
• HHS | NIH | NIAID | Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases (DMID)

• Energy disorder
• Liver failure
• Metabonomics
• Mitochondrial dysfunction
• α-Amatoxin

• Amanitins
• Animals
• Cell Line
• Chemical and Drug Induced Liver Injury/etiology
• Chemical and Drug Induced Liver Injury/metabolism
• Chemical and Drug Induced Liver Injury/pathology
• Disease Models, Animal
• Energy Metabolism
• Humans
• Liver/metabolism
• Liver/pathology
• Liver Failure/chemically induced
• Liver Failure/metabolism
• Liver Failure/pathology
• Metabolomics
• Mice, Inbred BALB C
• Mitochondria, Liver/metabolism
• Mitochondria, Liver/pathology
• Mushroom Poisoning/etiology
• Mushroom Poisoning/metabolism
• Mushroom Poisoning/pathology
• Time Factors
• Mice

• 2DLC-MS
• GC × GC-MS
• case-control study
• colorectal cancer
• untargeted metabolomics

• P30CA022453; R01CA93817; 1P20GM113226; S10OD020106. NIH HHS

The understanding into the pathogenesis and treatment of gastric cancer has improved in recent years; however, a number of limitations have delayed the development of effective treatment. Cancer cells can undergo glycolysis and inhibit oxidative phosphorylation in the presence of oxygen (Warburg effect). Previous studies have demonstrated that a rotary cell culture system (RCCS) can induce glycolytic metabolism. In addition, the potential of regulating cancer cells by targeting their metabolites has led to the rapid development of metabolomics. In the present study, human HGC-27 gastric cancer cells were cultured in a RCCS bioreactor, simulating weightlessness. Subsequently, liquid chromatography-mass spectrometry was used to examine the effects of simulated microgravity (SMG) on the metabolism of HGC-27 cells. A total of 67 differentially regulated metabolites were identified, including upregulated and downregulated metabolites. Compared with the normal gravity group, phosphatidyl ethanolamine, phosphatidyl choline, arachidonic acid and sphinganine were significantly upregulated in SMG conditions, whereas sphingomyelin, phosphatidyl serine, phosphatidic acid, L-proline, creatine, pantothenic acid, oxidized glutathione, adenosine diphosphate and adenosine triphosphate were significantly downregulated. The Human Metabolome Database compound analysis revealed that lipids and lipid-like metabolites were primarily affected in an SMG environment in the present study. Overall, the findings of the present study may aid our understanding of gastric cancer by identifying the underlying mechanisms of metabolism of the disease under SMG.

• HGC-27
• PA
• PC
• PE
• PS
• RCCS
• SM
• SMG
• metabolism

We have previously designed the anti-cancer food scoring model (ACFS) 1.0, an evidence-based quantitative tool analyzing the anti-cancer or carcinogenic potential of diets. Analysis was performed using simple quantitative indexes divided into 6 categories (S, A, B, C, D, and E). In this study, we applied this scoring model to wider recipes and evaluated its nutritional relevance.

National or known regional databases were searched for recipes from 6 categories: Korean out-dining, Korean home-dining, Western, Chinese, Mediterranean, and vegetarian. These recipes were scored using the ACFS formula and the nutrition profiles were analyzed.

Eighty-eight international recipes were analyzed. All S-graded recipes were from vegetarian or Mediterranean categories. The median code values of each category were B (Korean home-dining), C (Korean out-dining), B (Chinese), A (Mediterranean), S (vegetarian), and D (Western). The following profiles were correlated (P < 0.05) with ACFS grades in the univariate trend analysis: total calories, total fat, animal fat, animal protein, total protein, vitamin D, riboflavin, niacin, vitamin B₁₂, pantothenic acid, sodium, animal iron, zinc, selenium, and cholesterol (negative trends), and carbohydrate rate, fiber, water-soluble fiber, vitamin K, vitamin C, and plant calcium (positive trends). Multivariate analysis revealed that animal fat, animal iron, and niacin (negative trends) and animal protein, fiber, and vitamin C (positive trends) were statistically significant. Pantothenic acid and sodium showed non-significant negative trends (P < 0.1), and vitamin B₁₂ showed a non-significant positive trend.

This study provided a nutritional basis and extended the utility of ACFS, which is a bridgehead for future cancer-preventive clinical trials using ACFS.

• Cancer
• diet
• food
• prevention
• scoring model

• PPAR-alpha
• PPAR-gamma
• oxidative stress
• pro-inflammatory role
• protective role
• urinary biomarker
• vanin 1

• Amidohydrolases/analysis
• Amidohydrolases/metabolism
• Animals
• GPI-Linked Proteins/analysis
• GPI-Linked Proteins/metabolism
• Humans
• Inflammation/metabolism
• Inflammation/physiopathology
• Intestinal Diseases/metabolism
• Intestinal Diseases/physiopathology
• Intestines/physiopathology
• Kidney/metabolism
• Kidney/physiopathology
• Kidney Diseases/metabolism
• Kidney Diseases/physiopathology
• Liver/metabolism
• Liver/physiopathology
• Liver Diseases/metabolism
• Liver Diseases/physiopathology
• Oxidative Stress

• Metabolomics
• Prognostic biomarkers
• Prostate cancer
• SBRT

Medulloblastoma, the most common primary pediatric malignant brain tumor, originates in the posterior fossa of the brain. Pineoblastoma, which originates within the pineal gland, is a rarer malignancy that also presents in the pediatric population. Medulloblastoma and pineoblastoma exhibit overlapping clinical features and have similar histopathological characteristics. Histopathological similarities confound rapid diagnoses of these two tumor types. We have conducted a pilot feasibility study analyzing the molecular profile of archived frozen human tumor specimens using mass spectrometry imaging (MSI) to identify potential biomarkers capable of classifying and distinguishing between medulloblastoma and pineoblastoma.

We performed matrix-assisted laser desorption ionization Fourier transform ion cyclotron resonance mass spectrometry imaging on eight medulloblastoma biopsy specimens and three pineoblastoma biopsy specimens. Multivariate statistical analyses were performed on the MSI dataset to generate classifiers that distinguish the two tumor types. Lastly, the molecules that were discriminative of tumor type were queried against the Lipid Maps database and identified.

In this pilot study we show that medulloblastoma and pineoblastoma can be discriminated using molecular profiles determined by MSI. The highest-ranking discriminating classifiers of medulloblastoma and pineoblastoma were glycerophosphoglycerols and sphingolipids, respectively.

We demonstrate proof-of-concept that medulloblastoma and pineoblastoma can be rapidly distinguished by using MSI lipid profiles. We identified biomarker candidates capable of distinguishing these two histopathologically similar tumor types. This work expands the current molecular knowledge of medulloblastoma and pineoblastoma by characterizing their lipidomic profiles, which may be useful for developing novel diagnostic, prognostic and therapeutic strategies.

The online version of this article (10.1007/s11060-018-2978-2) contains supplementary material, which is available to authorized users.

• Biomarkers
• Brain tumors
• Lipids
• Mass spectrometry imaging
• Medulloblastoma
• Pineoblastoma

Despite new progress of chemotherapy in multiple myeloma (MM) clinical treatment, MM is still a refractory disease and new technology is needed to improve the outcomes and prolong the survival. Cold atmospheric plasma is a rapidly developed technology in recent years, which has been widely applied in biomedicine. Although plasma could efficiently inactivate various tumor cells, the effects of plasma on tumor cell metabolism have not been studied yet.

In this study, we investigated the metabolite profiling of He plasma treatment on myeloma tumor cells by gas-chromatography time-of-flight (GC-TOF) mass-spectrometry. Meanwhile, by bioinformatic analysis such as GO and KEGG analysis we try to figure out the metabolism pathway that was significantly affected by gas plasma treatment.

By GC-TOF mass-spectrometry, 573 signals were detected and evaluated using PCA and OPLS-DA. By KEGG analysis we listed all the differential metabolites and further classified into different metabolic pathways. The results showed that beta-alanine metabolism pathway was the most significant change after He gas plasma treatment in myeloma cells. Besides, propanoate metabolism and linoleic acid metabolism should also be concerned during gas plasma treatment of cancer cells.

Cold atmospheric plasma treatment could significantly alter the metabolite profiling of myeloma tumor cells, among which, the beta-alanine metabolism pathway is the most susceptible to He gas plasma treatment.

The online version of this article (10.1186/s12935-018-0541-z) contains supplementary material, which is available to authorized users.

• Beta-Alanine metabolism
• Cold atmospheric plasma
• KEGG analysis
• Mass spectrometry
• Metabolite profiling
• Multiple myeloma

• Clostridium butyricum
• Gas chromatography/mass spectrometry
• Irritable bowel syndrome
• Metabolite

• Animals
• Chromatography, Gas/methods
• Clostridium butyricum/physiology
• Disease Models, Animal
• Disease Progression
• Feces/chemistry
• Female
• Gastrointestinal Microbiome/physiology
• Humans
• Irritable Bowel Syndrome/etiology
• Irritable Bowel Syndrome/metabolism
• Irritable Bowel Syndrome/microbiology
• Irritable Bowel Syndrome/therapy
• Mass Spectrometry/methods
• Metabolome/physiology
• Metabolomics/methods
• Mice
• Mice, Inbred C57BL
• Probiotics/therapeutic use
• Reproducibility of Results
• Sensitivity and Specificity
• Stress, Psychological/complications
• Water

• everolimus
• mTOR
• metabolon
• ovarian cancer
• proliferation

• ATP
• Cancer
• Cell viability
• LDH
• β-Alanine

• GC-MS profiling
• body odor
• rhesus macaques
• semivolatile organic compounds (sVOCs)
• validation of swab sampling
• volatile organic compounds (VOCs)