Identification of biomarkers for apoptosis in cancer cell lines using metabolomics: tools for individualized medicine.

Abstract:

BACKGROUND:Metabolomics is a versatile unbiased method to search for biomarkers of human disease. In particular, one approach in cancer therapy is to promote apoptosis in tumour cells; this could be improved with specific biomarkers of apoptosis for monitoring treatment. We recently observed specific metabolic patterns in apoptotic cell lines; however, in that study, apoptosis was only induced with one pro-apoptotic agent, staurosporine. OBJECTIVE:The aim of this study was to find novel biomarkers of apoptosis by verifying our previous findings using two further pro-apoptotic agents, 5-fluorouracil and etoposide, that are commonly used in anticancer treatment. METHODS:Metabolic parameters were assessed in HepG2 and HEK293 cells using the newborn screening assay adapted for cell culture approaches, quantifying the levels of amino acids and acylcarnitines with mass spectrometry. RESULTS:We were able to identify apoptosis-specific changes in the metabolite profile. Moreover, the amino acids alanine and glutamate were both significantly up-regulated in apoptotic HepG2 and HEK293 cells irrespective of the apoptosis inducer. CONCLUSION:Our observations clearly indicate the potential of metabolomics in detecting metabolic biomarkers applicable in theranostics and for monitoring drug efficacy.

journal_name

J Intern Med

authors

Halama A,Riesen N,Möller G,Hrabě de Angelis M,Adamski J

doi

10.1111/joim.12117

subject

Has Abstract

pub_date

2013-11-01 00:00:00

pages

425-39

issue

5

eissn

0954-6820

issn

1365-2796

journal_volume

274

pub_type

杂志文章
  • Combination of budesonide/formoterol more effective than fluticasone/salmeterol in preventing exacerbations in chronic obstructive pulmonary disease: the PATHOS study.

    abstract:OBJECTIVES:Combinations of inhaled corticosteroids (ICSs) and long-acting β2 -agonists (LABAs) are recommended for patients with moderate and severe chronic obstructive pulmonary disease (COPD). However, it is not known whether different fixed combinations are equally effective. The aim of this study was to investigate...

    journal_title:Journal of internal medicine

    pub_type: 杂志文章

    doi:10.1111/joim.12067

    authors: Larsson K,Janson C,Lisspers K,Jørgensen L,Stratelis G,Telg G,Ställberg B,Johansson G

    更新日期:2013-06-01 00:00:00

  • Hypertriglyceridaemia due to genetic defects in lipoprotein lipase and apolipoprotein C-II.

    abstract::Hypertriglyceridaemia, as defined by fasting triglyceride levels of greater than 2.8 mmol l-1, is a prevalent dyslipoproteinaemia in our population. The underlying pathophysiological mechanisms that result in elevations of plasma triglycerides are heterogeneous and, in most cases, incompletely understood. However, in ...

    journal_title:Journal of internal medicine

    pub_type: 杂志文章,评审

    doi:10.1111/j.1365-2796.1992.tb01256.x

    authors: Fojo SS,Brewer HB

    更新日期:1992-06-01 00:00:00

  • Effect of lifibrol on the metabolism of low density lipoproteins and cholesterol.

    abstract::Lifibrol is a powerful cholesterol-lowering drug of unknown mechanism of action. This investigation was carried out to determine whether the major action of lifibrol is to enhance clearance of low density lipoproteins (LDL) through the LDL-receptor pathway, and if so, whether the drug exerts its action by altering the...

    journal_title:Journal of internal medicine

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1046/j.1365-2796.1999.00536.x

    authors: Vega GL,von Bergmann K,Grundy SM,Blumenschein S,Carter NB,Laeis P,Lindenthal B,von Bergmann J,Simatupang A,Lutjohann D,Adams-Huet B

    更新日期:1999-07-01 00:00:00

  • Associations between pituitary-adrenocortical function and abdominal obesity, hyperinsulinaemia and dyslipidaemia in normotensive males.

    abstract:OBJECTIVES:To examine the relationships between pituitary-adrenal cortical (PA) function, abdominal obesity, hyperinsulinaemia, and dyslipidaemia. DESIGN:A prospective study. SETTING:Helsinki University Central Hospital, Finland. SUBJECTS:Seventy-one healthy males aged 30-55 years. MAIN OUTCOME MEASURES:Insulin sen...

    journal_title:Journal of internal medicine

    pub_type: 杂志文章

    doi:10.1111/j.1365-2796.1997.tb00002.x

    authors: Hautanen A,Räikkönen K,Adlercreutz H

    更新日期:1997-06-01 00:00:00

  • Combined effects of obesity and physical activity in predicting mortality among men.

    abstract:OBJECTIVE:We evaluated the hypothesis that higher levels of total daily physical activity can eliminate the increased mortality rate associated with overweight and obesity. DESIGN:Population-based prospective cohort study. SETTING:Central Sweden. SUBJECTS:A total of 37,633 men at baseline 45-79 years of age and free...

    journal_title:Journal of internal medicine

    pub_type: 杂志文章

    doi:10.1111/j.1365-2796.2008.01985.x

    authors: Orsini N,Bellocco R,Bottai M,Pagano M,Michaelsson K,Wolk A

    更新日期:2008-11-01 00:00:00

  • Nicotine infusion acutely impairs insulin sensitivity in type 2 diabetic patients but not in healthy subjects.

    abstract:OBJECTIVES:The aim of this study was to examine if an acute nicotine infusion alters insulin sensitivity to a similar degree in type 2 diabetic patients as in healthy control subjects. DESIGN:. Double-blind, cross-over, placebo-controlled, randomized experimental study. Nicotine 0.3 microg kg-1 min(-1) or NaCl was inf...

    journal_title:Journal of internal medicine

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1046/j.1365-2796.2001.00840.x

    authors: Axelsson T,Jansson PA,Smith U,Eliasson B

    更新日期:2001-06-01 00:00:00

  • When to initiate and discontinue biologic treatments for rheumatoid arthritis?

    abstract::The introduction of biologic therapies heralded a new era in the treatment for chronic inflammatory autoimmune diseases of which rheumatoid arthritis is one of the most prevalent. From a scientific point of view, these therapies demonstrated that the targeting of individual cytokines or cell-surface markers is a very ...

    journal_title:Journal of internal medicine

    pub_type: 杂志文章,评审

    doi:10.1111/j.1365-2796.2011.02355.x

    authors: Chatzidionysiou K,van Vollenhoven RF

    更新日期:2011-06-01 00:00:00

  • Pulsatile insulin infusion and glucose-homeostasis in well-controlled type 1 (insulin-dependent) diabetic patients.

    abstract::Pulsatile, intravenous insulin infusion designed to mimic the portal insulin concentrations that emerge physiologically after a meal, has been postulated to improve glucose tolerance in Type 1 (insulin-dependent) diabetic patients. We studied the effects of insulin pulsing (10 i.v. pulses of human insulin of 0.035 U k...

    journal_title:Journal of internal medicine

    pub_type: 杂志文章

    doi:10.1111/j.1365-2796.1989.tb01403.x

    authors: Heinemann L,Sonnenberg GE,Hohmann A,Ritzenhoff A,Berger M,Benn J,Sönksen P,Kelley D,Gerich J,Aoki T

    更新日期:1989-11-01 00:00:00

  • Neutrophil granules in health and disease.

    abstract::Neutrophil granules store proteins that are critically important for the neutrophil to move from the vascular bed to tissues and to kill microorganisms. This is illustrated in nature when individual proteins are deleted due to inherited mutations of their cognate genes, and such deficiencies result in the conditions l...

    journal_title:Journal of internal medicine

    pub_type: 杂志文章,评审

    doi:10.1111/j.1365-2796.2010.02237.x

    authors: Häger M,Cowland JB,Borregaard N

    更新日期:2010-07-01 00:00:00

  • The risk of hip fractures in patients with primary hyperparathyroidism: a population-based cohort study with a follow-up of 19 years.

    abstract:OBJECTIVE:To evaluate primary hyperparathyroidism (HPT) as a risk factor for hip fractures. DESIGN:A population-based, record-linked, prospective study with a mean observation time of 17 years (women) and 16.5 years (men). SETTING:A cohort obtained from a register of hospital admissions in the Uppsala Health Care Reg...

    journal_title:Journal of internal medicine

    pub_type: 杂志文章

    doi:10.1111/j.1365-2796.1993.tb01017.x

    authors: Larsson K,Ljunghall S,Krusemo UB,Naessén T,Lindh E,Persson I

    更新日期:1993-12-01 00:00:00

  • Family burden of cardiovascular mortality: risk implications for offspring in a national register linkage study based upon the Malmö Preventive Project.

    abstract:OBJECTIVE:To investigate the adjusted relative risk of cardiovascular disease (CVD) events in offspring of parents with cardiovascular mortality before 75 years. SETTING:The city of Malmö, Sweden. DESIGN:A follow-up study based on register linkage analyses. SUBJECTS AND METHODS:In the Malmö Preventive Project (MPP),...

    journal_title:Journal of internal medicine

    pub_type: 杂志文章

    doi:10.1046/j.1365-2796.2003.01287.x

    authors: Nilsson PM,Nilsson JA,Berglund G

    更新日期:2004-02-01 00:00:00

  • Prions and protein-folding diseases.

    abstract::Prions represent a group of proteins with a unique capacity to fold into different conformations. One isoform is rich in beta-pleated sheets and can aggregate into amyloid that may be pathogenic. This abnormal form propagates itself by imposing its confirmation on the homologous normal host cell protein. Pathogenic pr...

    journal_title:Journal of internal medicine

    pub_type: 杂志文章,评审

    doi:10.1111/j.1365-2796.2011.02387.x

    authors: Norrby E

    更新日期:2011-07-01 00:00:00

  • Cadmium exposure is accompanied by increased prevalence and future growth of atherosclerotic plaques in 64-year-old women.

    abstract:OBJECTIVES:There is currently widespread exposure to the toxic metal cadmium through the diet as well as through smoking, and it has been suggested that cadmium exposure may increase the risk of cardiovascular disease. Here we examined whether cadmium exposure is associated with prevalence and growth of atherosclerotic...

    journal_title:Journal of internal medicine

    pub_type: 杂志文章

    doi:10.1111/j.1365-2796.2012.02578.x

    authors: Fagerberg B,Bergström G,Borén J,Barregard L

    更新日期:2012-12-01 00:00:00

  • Unsuspected osteomyelitis is frequent in persistent diabetic foot ulcer and better diagnosed by MRI than by 18F-FDG PET or 99mTc-MOAB.

    abstract:AIM:Prevalence, optimal diagnostic approach and consequences of clinically unsuspected osteomyelitis in diabetic foot ulcers are unclear. Early diagnosis of this infection may be crucial to ensure correct management. METHODS:We conducted a prospective study in 20 diabetic patients with a chronic foot ulcer (>8 weeks) ...

    journal_title:Journal of internal medicine

    pub_type: 临床试验,杂志文章

    doi:10.1111/j.1365-2796.2007.01877.x

    authors: Schwegler B,Stumpe KD,Weishaupt D,Strobel K,Spinas GA,von Schulthess GK,Hodler J,Böni T,Donath MY

    更新日期:2008-01-01 00:00:00

  • The role of clonal haematopoiesis in cardiovascular diseases: epidemiology and experimental studies.

    abstract::Clonal haematopoiesis results from acquired mutations in haematopoietic stem and progenitor cells (HSPCs). These mutations can confer the HSPC with a competitive advantage, leading to their clonal expansion within the limiting bone marrow niche. This process is often insufficient to produce a haematologic malignancy; ...

    journal_title:Journal of internal medicine

    pub_type: 杂志文章

    doi:10.1111/joim.13130

    authors: Min KD,Kour A,Sano S,Walsh K

    更新日期:2020-11-01 00:00:00

  • Effects of long-term treatment with metoprolol and hydrochlorothiazide on plasma lipids and lipoproteins.

    abstract::In order to evaluate the effects of one-year antihypertensive treatment on plasma lipids and lipoproteins, 65 patients whose diastolic blood pressure was in the range 95-120 mmHg were randomly allocated to groups that received either hydrochlorothiazide or metoprolol, or both drugs when the response to one of them was...

    journal_title:Journal of internal medicine

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1111/j.1365-2796.1990.tb00240.x

    authors: Monmany J,Domingo P,Gomez JA,Sanz F,Roca-Cusachs A,Nolla J,Jane F

    更新日期:1990-10-01 00:00:00

  • Should children or young adults be screened for serum lipid levels to prevent adult coronary heart disease? Experience from the Cardiovascular Risk in Young Finns study.

    abstract::Coronary heart disease (CHD) has its origin in childhood. High cholesterol levels measured in children and adolescents are indicative of concurrent atherosclerotic changes and probably predict adult coronary heart disease. We review here the relevance of screening children, adolescents or young adults for serum lipid ...

    journal_title:Journal of internal medicine

    pub_type: 杂志文章,评审

    doi:10.1111/j.1365-2796.1994.tb01273.x

    authors: Porkka KV,Viikari JS

    更新日期:1994-08-01 00:00:00

  • Outcomes of endovascular treatment for acute large-vessel ischaemic stroke more than 6 h after symptom onset.

    abstract:BACKGROUND AND OBJECTIVES:Benefit from endovascular thrombectomy (EVT) for large-vessel occlusion (LVO) acute ischaemic stroke (AIS) is well demonstrated. Furthermore, emerging evidence supports efficacy in appropriately selected patients treated beyond current recommendations of 6 h. We evaluated clinical outcomes in ...

    journal_title:Journal of internal medicine

    pub_type: 杂志文章,多中心研究

    doi:10.1111/joim.12680

    authors: Motyer R,Kok HK,Asadi H,O'Hare A,Brennan P,Power S,Looby S,Nicholson P,Williams D,Murphy S,Hill MD,Goyal M,McManus J,O'Brien P,Thornton J

    更新日期:2017-12-01 00:00:00

  • Subacute cor pulmonale due to microscopic pulmonary tumour cell embolization.

    abstract::A case of a clinically occult ovarian carcinoma leading to subacute cor pulmonale in a 62-year-old woman is described. The patient was admitted to hospital with increasing respiratory distress. Physical examination and echocardiography showed signs of pulmonary hypertension. She died from circulatory failure. Autopsy ...

    journal_title:Journal of internal medicine

    pub_type: 杂志文章

    doi:10.1111/j.1365-2796.1994.tb00852.x

    authors: Lambert-Jensen P,Mertz H,Nyvad O,Christensen JH

    更新日期:1994-11-01 00:00:00

  • Lipid lowering in severe familial hypercholesterolaemia: efficacy and safety of a new regenerating system for selective apheresis of apolipoprotein B-containing lipoproteins.

    abstract::Preliminary experience of the efficacy and safety of a new regenerating system for selective extracorporeal removal of apolipoprotein B-containing lipoproteins is described. Four patients with familial hyperlipoproteinaemia were studied on 10 occasions. A system of two, parallel, dextran sulphate cellulose columns was...

    journal_title:Journal of internal medicine

    pub_type: 杂志文章

    doi:10.1111/j.1365-2796.1989.tb00032.x

    authors: Eriksson M,Berg B,Berglund L,Lantz B,Angelin B

    更新日期:1989-01-01 00:00:00

  • Oral anticoagulation in nonvalvular atrial fibrillation.

    abstract::Chronic nonvalvular atrial fibrillation is associated with an overall risk of thromboembolic complications of 4.5% per year. Advancing age, prior stroke or transient cerebral ischaemia, diabetes, hypertension, and impaired function of the left ventricle are known risk factors. Placebo-controlled trials have demonstrat...

    journal_title:Journal of internal medicine

    pub_type: 杂志文章,评审

    doi:10.1046/j.1365-2796.1999.00461.x

    authors: Koefoed BG,Petersen P

    更新日期:1999-04-01 00:00:00

  • Clinical symptoms in young adults with atypical chest pain attending the emergency department.

    abstract::Clinical symptoms were studied in 69 consecutive patients below the age of 40 years who were attending the emergency unit because of unexplained chest pain. In a structured interview a few weeks after the emergency visit, only one-third of the patients reported that they believed in the doctor's diagnosis; they believ...

    journal_title:Journal of internal medicine

    pub_type: 杂志文章

    doi:10.1111/j.1365-2796.1991.tb00442.x

    authors: Roll M,Kollind M,Theorell T

    更新日期:1991-09-01 00:00:00

  • Studies on patients establish Crohn's disease as a manifestation of impaired innate immunity.

    abstract::The fruitless search for the cause of Crohn's disease has been conducted for more than a century. Various theories, including autoimmunity, mycobacterial infection and aberrant response to food and other ingested materials, have been abandoned for lack of robust proof. This review will provide the evidence, obtained f...

    journal_title:Journal of internal medicine

    pub_type: 杂志文章,评审

    doi:10.1111/joim.12945

    authors: Segal AW

    更新日期:2019-10-01 00:00:00

  • The Swedish Twin Registry: a unique resource for clinical, epidemiological and genetic studies.

    abstract::The Swedish Twin Registry (STR), which today has developed into a unique resource, was first established in the late 1950s to study the importance of smoking and alcohol consumption on cancer and cardiovascular diseases whilst controlling for genetic propensity to disease. Since that time, the Registry has been expand...

    journal_title:Journal of internal medicine

    pub_type: 杂志文章,评审

    doi:10.1046/j.1365-2796.2002.01032.x

    authors: Lichtenstein P,De Faire U,Floderus B,Svartengren M,Svedberg P,Pedersen NL

    更新日期:2002-09-01 00:00:00

  • Exercise counteracts lipotoxicity by improving lipid turnover and lipid droplet quality.

    abstract::The incidence of obesity and metabolic disease, such as type 2 diabetes mellitus (T2D), is rising globally. Dietary lipid over supply leads to lipid accumulation at ectopic sites, such as skeletal muscle. Ectopic lipid storage is highly correlated with insulin resistance and T2D, likely due to a loss of metabolic flex...

    journal_title:Journal of internal medicine

    pub_type: 杂志文章,评审

    doi:10.1111/joim.12729

    authors: Zacharewicz E,Hesselink MKC,Schrauwen P

    更新日期:2018-11-01 00:00:00

  • Adverse renal effects of anti-inflammatory agents: evaluation of selective and nonselective cyclooxygenase inhibitors.

    abstract::Conventional nonsteroidal anti-inflammatory drugs (NSAIDs), i.e. nonselective cyclooxygenase COX inhibitors have well-documented nephrotoxicity. Adverse renal effects occur because of inhibition of the synthesis of cyclooxygenase-derived prostaglandins which act to modulate pathologic processes that would normally imp...

    journal_title:Journal of internal medicine

    pub_type: 杂志文章,评审

    doi:10.1046/j.1365-2796.2003.01146.x

    authors: Gambaro G,Perazella MA

    更新日期:2003-06-01 00:00:00

  • Atrial fibrillation or flutter and stroke: a Danish population-based study of the effectiveness of oral anticoagulation in clinical practice.

    abstract:OBJECTIVES:A pooled analysis of randomized trials has shown that oral anticoagulation therapy reduces the risk of ischaemic stroke with 68% in patients with atrial fibrillation. We examined the effectiveness of oral anticoagulation on risk of stroke of any nature (fatal and nonfatal ischaemic and/or haemorrhagic stroke...

    journal_title:Journal of internal medicine

    pub_type: 杂志文章

    doi:10.1046/j.1365-2796.2002.01009.x

    authors: Frost L,Johnsen SP,Pedersen L,Toft E,Husted S,Sørensen HT

    更新日期:2002-07-01 00:00:00

  • The occurrence of malignant disease in adult nephrotic syndrome.

    abstract::The aim of the present study was to determine the incidence of malignant disease (MD) in adult patients with nephrotic syndrome (NS). Eighty-eight consecutive patients (38 females; 50 males; mean age 47 years; range 15-86) seen in a renal clinic in a 13-year period with NS were studied. Eight of the patients had or de...

    journal_title:Journal of internal medicine

    pub_type: 杂志文章

    doi:10.1111/j.1365-2796.1989.tb01380.x

    authors: Lund L,Jacobsen BA,Schmidt EB

    更新日期:1989-09-01 00:00:00

  • Early postoperative basal serum GH level and the GH response to TRH in relation to the long-term outcome of surgical treatment for acromegaly: a report on 39 patients.

    abstract::During a 10-year period 39 patients with acromegaly, aged 23-73 years, underwent selective adenomectomy via a trans-sphenoidal or transfrontal (one case) approach. Six to 12 months after the operation, the serum level of growth hormone (GH) was reduced to less than 5 micrograms l-1 in 28 patients (74%) in at least two...

    journal_title:Journal of internal medicine

    pub_type: 杂志文章

    doi:10.1111/j.1365-2796.1991.tb00405.x

    authors: Valdemarsson S,Bramnert M,Cronquist S,Elner A,Eneroth CM,Hedner P,Lindvall-Axelsson M,Nordström CH,Strömblad LG

    更新日期:1991-07-01 00:00:00

  • Clinical value of gallium-67 SPECT scintigraphy in the diagnostic and therapeutic evaluation of retroperitoneal fibrosis: a prospective study.

    abstract:BACKGROUND:Gallium-67 (67Ga) scintigraphy may be useful in evaluating patients with retroperitoneal fibrosis (RPF), but a systematic assessment of its value is lacking. OBJECTIVE:Prospective evaluation of the value of 67Ga scintigraphy in assessing active RPF disease and in predicting treatment response. METHODS:Thir...

    journal_title:Journal of internal medicine

    pub_type: 杂志文章

    doi:10.1111/j.1365-2796.2007.01805.x

    authors: van Bommel EF,Siemes C,van der Veer SJ,Han SH,Huiskes AW,Hendriksz TR

    更新日期:2007-08-01 00:00:00