LIVIVO - Search results -

Search results

Result 1 - 10 of total 22

Search options

Article ; Online: The aging tumor metabolic microenvironment.

Pilley, Steven E / Esparza, Edgar / Mullen, Peter J

2023 Volume 84, Page(s) 102995

Abstract: Despite the higher incidence of cancer with increasing age, few preclinical or clinical studies incorporate age. This, coupled with an aging world population, requires that we improve our understanding of how aging affects cancer development, progression, ...

Abstract	Despite the higher incidence of cancer with increasing age, few preclinical or clinical studies incorporate age. This, coupled with an aging world population, requires that we improve our understanding of how aging affects cancer development, progression, and treatment. One key area will be how the tumor microenvironment (TME) changes with age. Metabolite levels are an essential component of the TME, and they are affected by the metabolic requirements of the cells present and systemic metabolite availability. These factors are affected by aging, causing different TME metabolic states between young and older adults. In this review, we will summarize what is known about how aging impacts the TME metabolic state, and suggest how we can improve our understanding of it.
MeSH term(s)	Humans ; Aged ; Tumor Microenvironment ; Neoplasms/therapy
Language	English
Publishing date	2023-09-30
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1052045-4
ISSN	1879-0429 ; 0958-1669
ISSN (online)	1879-0429
ISSN	0958-1669
DOI	10.1016/j.copbio.2023.102995
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3071: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Methionine restriction forces Epstein-Barr virus out of latency.

Kashyap, Sriraksha Bharadwaj / Mulondo, Racheal / Mullen, Peter J

Cell metabolism

2022 Volume 34, Issue 9, Page(s) 1229–1231

Abstract: EBV gene expression is repressed during viral latency to prevent an immune response, but it is not known how metabolism contributes to this silencing. In this issue of Cell Metabolism, Guo et al. describe how methionine restriction reactivates the ... ...

Abstract	EBV gene expression is repressed during viral latency to prevent an immune response, but it is not known how metabolism contributes to this silencing. In this issue of Cell Metabolism, Guo et al. describe how methionine restriction reactivates the expression of EBV genes, offering new therapeutic approaches against EBV-driven diseases.
MeSH term(s)	Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Humans ; Methionine ; Virus Latency
Chemical Substances	Methionine (AE28F7PNPL)
Language	English
Publishing date	2022-09-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2176834-1
ISSN	1932-7420 ; 1550-4131
ISSN (online)	1932-7420
ISSN	1550-4131
DOI	10.1016/j.cmet.2022.08.009
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 6169: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Asparagine couples mitochondrial respiration to ATF4 activity and tumor growth.

Krall, Abigail S / Mullen, Peter J / Surjono, Felicia / Momcilovic, Milica / Schmid, Ernst W / Halbrook, Christopher J / Thambundit, Apisadaporn / Mittelman, Steven D / Lyssiotis, Costas A / Shackelford, David B / Knott, Simon R V / Christofk, Heather R

Cell metabolism

2021 Volume 33, Issue 5, Page(s) 1013–1026.e6

Abstract: Mitochondrial respiration is critical for cell proliferation. In addition to producing ATP, respiration generates biosynthetic precursors, such as aspartate, an essential substrate for nucleotide synthesis. Here, we show that in addition to depleting ... ...

Abstract	Mitochondrial respiration is critical for cell proliferation. In addition to producing ATP, respiration generates biosynthetic precursors, such as aspartate, an essential substrate for nucleotide synthesis. Here, we show that in addition to depleting intracellular aspartate, electron transport chain (ETC) inhibition depletes aspartate-derived asparagine, increases ATF4 levels, and impairs mTOR complex I (mTORC1) activity. Exogenous asparagine restores proliferation, ATF4 and mTORC1 activities, and mTORC1-dependent nucleotide synthesis in the context of ETC inhibition, suggesting that asparagine communicates active respiration to ATF4 and mTORC1. Finally, we show that combination of the ETC inhibitor metformin, which limits tumor asparagine synthesis, and either asparaginase or dietary asparagine restriction, which limit tumor asparagine consumption, effectively impairs tumor growth in multiple mouse models of cancer. Because environmental asparagine is sufficient to restore tumor growth in the context of respiration impairment, our findings suggest that asparagine synthesis is a fundamental purpose of tumor mitochondrial respiration, which can be harnessed for therapeutic benefit to cancer patients.
MeSH term(s)	Activating Transcription Factor 4/metabolism ; Animals ; Asparagine/metabolism ; Asparagine/pharmacology ; Aspartic Acid/deficiency ; Aspartic Acid/pharmacology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Diet/veterinary ; Electron Transport Chain Complex Proteins/antagonists & inhibitors ; Electron Transport Chain Complex Proteins/metabolism ; Humans ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Metformin/pharmacology ; Metformin/therapeutic use ; Mice ; Mice, Inbred NOD ; Mitochondria/drug effects ; Mitochondria/metabolism ; Neoplasms/drug therapy ; Neoplasms/mortality ; Neoplasms/pathology ; Nucleotides/metabolism ; Survival Rate
Chemical Substances	Electron Transport Chain Complex Proteins ; Nucleotides ; Activating Transcription Factor 4 (145891-90-3) ; Aspartic Acid (30KYC7MIAI) ; Asparagine (7006-34-0) ; Metformin (9100L32L2N) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1)
Language	English
Publishing date	2021-02-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2176834-1
ISSN	1932-7420 ; 1550-4131
ISSN (online)	1932-7420
ISSN	1550-4131
DOI	10.1016/j.cmet.2021.02.001
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 6169: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: The interplay between cell signalling and the mevalonate pathway in cancer.

Mullen, Peter J / Yu, Rosemary / Longo, Joseph / Archer, Michael C / Penn, Linda Z

Nature reviews. Cancer

2016 Volume 16, Issue 11, Page(s) 718–731

Abstract: The mevalonate (MVA) pathway is an essential metabolic pathway that uses acetyl-CoA to produce sterols and isoprenoids that are integral to tumour growth and progression. In recent years, many oncogenic signalling pathways have been shown to increase the ...

Abstract	The mevalonate (MVA) pathway is an essential metabolic pathway that uses acetyl-CoA to produce sterols and isoprenoids that are integral to tumour growth and progression. In recent years, many oncogenic signalling pathways have been shown to increase the activity and/or the expression of MVA pathway enzymes. This Review summarizes recent advances and discusses unique opportunities for immediately targeting this metabolic vulnerability in cancer with agents that have been approved for other therapeutic uses, such as the statin family of drugs, to improve outcomes for cancer patients.
MeSH term(s)	Humans ; Metabolic Networks and Pathways ; Mevalonic Acid/metabolism ; Neoplasms/metabolism ; Signal Transduction
Chemical Substances	Mevalonic Acid (S5UOB36OCZ)
Language	English
Publishing date	2016
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2062767-1
ISSN	1474-1768 ; 1474-175X
ISSN (online)	1474-1768
ISSN	1474-175X
DOI	10.1038/nrc.2016.76
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5563: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 24: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: SARS-CoV-2 infection rewires host cell metabolism and is potentially susceptible to mTORC1 inhibition.

Mullen, Peter J / Garcia, Gustavo / Purkayastha, Arunima / Matulionis, Nedas / Schmid, Ernst W / Momcilovic, Milica / Sen, Chandani / Langerman, Justin / Ramaiah, Arunachalam / Shackelford, David B / Damoiseaux, Robert / French, Samuel W / Plath, Kathrin / Gomperts, Brigitte N / Arumugaswami, Vaithilingaraja / Christofk, Heather R

Nature communications

2021 Volume 12, Issue 1, Page(s) 1876

Abstract: Viruses hijack host cell metabolism to acquire the building blocks required for replication. Understanding how SARS-CoV-2 alters host cell metabolism may lead to potential treatments for COVID-19. Here we profile metabolic changes conferred by SARS-CoV-2 ...

Abstract	Viruses hijack host cell metabolism to acquire the building blocks required for replication. Understanding how SARS-CoV-2 alters host cell metabolism may lead to potential treatments for COVID-19. Here we profile metabolic changes conferred by SARS-CoV-2 infection in kidney epithelial cells and lung air-liquid interface (ALI) cultures, and show that SARS-CoV-2 infection increases glucose carbon entry into the TCA cycle via increased pyruvate carboxylase expression. SARS-CoV-2 also reduces oxidative glutamine metabolism while maintaining reductive carboxylation. Consistent with these changes, SARS-CoV-2 infection increases the activity of mTORC1 in cell lines and lung ALI cultures. Lastly, we show evidence of mTORC1 activation in COVID-19 patient lung tissue, and that mTORC1 inhibitors reduce viral replication in kidney epithelial cells and lung ALI cultures. Our results suggest that targeting mTORC1 may be a feasible treatment strategy for COVID-19 patients, although further studies are required to determine the mechanism of inhibition and potential efficacy in patients.
MeSH term(s)	Animals ; Benzamides/pharmacology ; COVID-19/pathology ; Cell Line ; Chlorocebus aethiops ; Citric Acid Cycle/physiology ; Glucose/metabolism ; Glutamine/metabolism ; HEK293 Cells ; Humans ; Lung/metabolism ; Lung/virology ; Mechanistic Target of Rapamycin Complex 1/antagonists & inhibitors ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Morpholines/pharmacology ; Naphthyridines/pharmacology ; Protein Kinase Inhibitors/pharmacology ; Pyrimidines/pharmacology ; Pyruvate Carboxylase/biosynthesis ; SARS-CoV-2/metabolism ; Vero Cells ; Virus Replication/drug effects
Chemical Substances	9-(6-aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo(h)(1,6)naphthyridin-2(1H)-one ; Benzamides ; Morpholines ; Naphthyridines ; Protein Kinase Inhibitors ; Pyrimidines ; vistusertib (0BSC3P4H5X) ; Glutamine (0RH81L854J) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Pyruvate Carboxylase (EC 6.4.1.1) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2021-03-25
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-22166-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Statin-Induced Cancer Cell Death Can Be Mechanistically Uncoupled from Prenylation of RAS Family Proteins.

Yu, Rosemary / Longo, Joseph / van Leeuwen, Jenna E / Mullen, Peter J / Ba-Alawi, Wail / Haibe-Kains, Benjamin / Penn, Linda Z

Cancer research

2017 Volume 78, Issue 5, Page(s) 1347–1357

Abstract: The statin family of drugs preferentially triggers tumor cell apoptosis by depleting mevalonate pathway metabolites farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP), which are used for protein prenylation, including the oncoproteins ... ...

Abstract	The statin family of drugs preferentially triggers tumor cell apoptosis by depleting mevalonate pathway metabolites farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP), which are used for protein prenylation, including the oncoproteins of the RAS superfamily. However, accumulating data indicate that activation of the RAS superfamily are poor biomarkers of statin sensitivity, and the mechanism of statin-induced tumor-specific apoptosis remains unclear. Here we demonstrate that cancer cell death triggered by statins can be uncoupled from prenylation of the RAS superfamily of oncoproteins. Ectopic expression of different members of the RAS superfamily did not uniformly sensitize cells to fluvastatin, indicating that increased cellular demand for protein prenylation cannot explain increased statin sensitivity. Although ectopic expression of HRAS increased statin sensitivity, expression of myristoylated HRAS did not rescue this effect. HRAS-induced epithelial-to-mesenchymal transition (EMT) through activation of zinc finger E-box binding homeobox 1 (ZEB1) sensitized tumor cells to the antiproliferative activity of statins, and induction of EMT by ZEB1 was sufficient to phenocopy the increase in fluvastatin sensitivity; knocking out ZEB1 reversed this effect. Publicly available gene expression and statin sensitivity data indicated that enrichment of EMT features was associated with increased sensitivity to statins in a large panel of cancer cell lines across multiple cancer types. These results indicate that the anticancer effect of statins is independent from prenylation of RAS family proteins and is associated with a cancer cell EMT phenotype.
MeSH term(s)	Apoptosis ; Biomarkers, Tumor ; Cell Proliferation ; Drug Resistance, Neoplasm/drug effects ; Epithelial-Mesenchymal Transition/drug effects ; Fluvastatin/pharmacology ; Humans ; Mevalonic Acid/metabolism ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Neoplasms/pathology ; Polyisoprenyl Phosphates/metabolism ; Protein Prenylation/drug effects ; Sesquiterpenes/metabolism ; Tumor Cells, Cultured ; Zinc Finger E-box-Binding Homeobox 1/genetics ; Zinc Finger E-box-Binding Homeobox 1/metabolism ; ras Proteins/genetics ; ras Proteins/metabolism
Chemical Substances	Biomarkers, Tumor ; Polyisoprenyl Phosphates ; Sesquiterpenes ; ZEB1 protein, human ; Zinc Finger E-box-Binding Homeobox 1 ; Fluvastatin (4L066368AS) ; farnesyl pyrophosphate (79W6B01D07) ; ras Proteins (EC 3.6.5.2) ; geranylgeranyl pyrophosphate (N21T0D88LX) ; Mevalonic Acid (S5UOB36OCZ)
Language	English
Publishing date	2017-12-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-17-1231
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uh III Zs.135/5: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Simvastatin induces mitochondrial dysfunction and increased atrogin-1 expression in H9c2 cardiomyocytes and mice in vivo.

Bonifacio, Annalisa / Mullen, Peter J / Mityko, Ileana Scurtu / Navegantes, Luiz C / Bouitbir, Jamal / Krähenbühl, Stephan

Archives of toxicology

2014 Volume 90, Issue 1, Page(s) 203–215

Abstract: Simvastatin is effective and well tolerated, with adverse reactions mainly affecting skeletal muscle. Important mechanisms for skeletal muscle toxicity include mitochondrial impairment and increased expression of atrogin-1. The aim was to study the ... ...

Abstract	Simvastatin is effective and well tolerated, with adverse reactions mainly affecting skeletal muscle. Important mechanisms for skeletal muscle toxicity include mitochondrial impairment and increased expression of atrogin-1. The aim was to study the mechanisms of toxicity of simvastatin on H9c2 cells (a rodent cardiomyocyte cell line) and on the heart of male C57BL/6 mice. After, exposure to 10 μmol/L simvastatin for 24 h, H9c2 cells showed impaired oxygen consumption, a reduction in the mitochondrial membrane potential and a decreased activity of several enzyme complexes of the mitochondrial electron transport chain (ETC). The cellular ATP level was also decreased, which was associated with phosphorylation of AMPK, dephosphorylation and nuclear translocation of FoxO3a as well as increased mRNA expression of atrogin-1. Markers of apoptosis were increased in simvastatin-treated H9c2 cells. Treatment of mice with 5 mg/kg/day simvastatin for 21 days was associated with a 5 % drop in heart weight as well as impaired activity of several enzyme complexes of the ETC and increased mRNA expression of atrogin-1 and of markers of apoptosis in cardiac tissue. Cardiomyocytes exposed to simvastatin in vitro or in vivo sustain mitochondrial damage, which causes AMPK activation, dephosphorylation and nuclear transformation of FoxO3a as well as increased expression of atrogin-1. Mitochondrial damage and increased atrogin-1 expression are associated with apoptosis and increased protein breakdown, which may cause myocardial atrophy.
MeSH term(s)	AMP-Activated Protein Kinases/metabolism ; Adenosine Triphosphate/metabolism ; Animals ; Apoptosis/drug effects ; Cardiotoxicity ; Cell Line ; Dose-Response Relationship, Drug ; Electron Transport Chain Complex Proteins/metabolism ; Energy Metabolism/drug effects ; Enzyme Activation ; Forkhead Box Protein O3 ; Forkhead Transcription Factors/metabolism ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/toxicity ; Male ; Membrane Potential, Mitochondrial/drug effects ; Mice, Inbred C57BL ; Mitochondria, Heart/drug effects ; Mitochondria, Heart/metabolism ; Mitochondria, Heart/pathology ; Muscle Proteins/metabolism ; Myocytes, Cardiac/drug effects ; Myocytes, Cardiac/metabolism ; Myocytes, Cardiac/pathology ; Phosphorylation ; Rats ; SKP Cullin F-Box Protein Ligases/metabolism ; Simvastatin/toxicity ; Time Factors ; Up-Regulation
Chemical Substances	Electron Transport Chain Complex Proteins ; FOXO3 protein, rat ; Forkhead Box Protein O3 ; Forkhead Transcription Factors ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Muscle Proteins ; Adenosine Triphosphate (8L70Q75FXE) ; Simvastatin (AGG2FN16EV) ; Fbxo32 protein, mouse (EC 2.3.2.27) ; Fbxo32 protein, rat (EC 2.3.2.27) ; SKP Cullin F-Box Protein Ligases (EC 2.3.2.27) ; AMP-Activated Protein Kinases (EC 2.7.11.31)
Language	English
Publishing date	2014-10-10
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	124992-7
ISSN	1432-0738 ; 0340-5761
ISSN (online)	1432-0738
ISSN	0340-5761
DOI	10.1007/s00204-014-1378-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Uf I Zs.90: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: A pilot window-of-opportunity study of preoperative fluvastatin in localized prostate cancer.

Longo, Joseph / Hamilton, Robert J / Masoomian, Mehdi / Khurram, Najia / Branchard, Emily / Mullen, Peter J / Elbaz, Mohamad / Hersey, Karen / Chadwick, Dianne / Ghai, Sangeet / Andrews, David W / Chen, Eric X / van der Kwast, Theodorus H / Fleshner, Neil E / Penn, Linda Z

Prostate cancer and prostatic diseases

2020 Volume 23, Issue 4, Page(s) 630–637

Abstract: Background: Statins inhibit HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway. Epidemiological and pre-clinical evidence support an association between statin use and delayed prostate cancer (PCa) progression. Here, we evaluated the ... ...

Abstract	Background: Statins inhibit HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway. Epidemiological and pre-clinical evidence support an association between statin use and delayed prostate cancer (PCa) progression. Here, we evaluated the effects of neoadjuvant fluvastatin treatment on markers of cell proliferation and apoptosis in men with localized PCa. Methods: Thirty-three men were treated daily with 80 mg fluvastatin for 4-12 weeks in a single-arm window-of-opportunity study between diagnosis of localized PCa and radical prostatectomy (RP) (ClinicalTrials.gov: NCT01992042). Percent Ki67 and cleaved Caspase-3 (CC3)-positive cells in tumor tissues were evaluated in 23 patients by immunohistochemistry before and after treatment. Serum and intraprostatic fluvastatin concentrations were quantified by liquid chromatography-mass spectrometry. Results: Baseline characteristics included a median prostate-specific antigen (PSA) level of 6.48 ng/mL (IQR: 4.21-10.33). The median duration of fluvastatin treatment was 49 days (range: 27-102). Median serum low-density lipoprotein levels decreased by 35% after treatment, indicating patient compliance. Median PSA decreased by 12%, but this was not statistically significant in our small cohort. The mean fluvastatin concentration measured in the serum was 0.2 μM (range: 0.0-1.1 μM), and in prostatic tissue was 8.5 nM (range: 0.0-77.0 nM). At these concentrations, fluvastatin induced PCa cell death in vitro in a dose- and time-dependent manner. In patients, fluvastatin treatment did not significantly alter intratumoral Ki67 positivity; however, a median 2.7-fold increase in CC3 positivity (95% CI: 1.9-5.0, p = 0.007) was observed in post-fluvastatin RP tissues compared with matched pre-treatment biopsy controls. In a subset analysis, this increase in CC3 was more pronounced in men on fluvastatin for >50 days. Conclusions: Fluvastatin prior to RP achieves measurable drug concentrations in prostatic tissue and is associated with promising effects on tumor cell apoptosis. These data warrant further investigation into the anti-neoplastic effects of statins in prostate tissue.
MeSH term(s)	Aged ; Apoptosis ; Biomarkers, Tumor/metabolism ; Caspase 3/metabolism ; Disease Progression ; Fluvastatin/therapeutic use ; Humans ; Hydroxymethylglutaryl CoA Reductases/metabolism ; Ki-67 Antigen/metabolism ; Male ; Middle Aged ; Neoadjuvant Therapy ; Pilot Projects ; Preoperative Care ; Prostatectomy/methods ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/metabolism ; Prostatic Neoplasms/pathology ; Prostatic Neoplasms/surgery
Chemical Substances	Biomarkers, Tumor ; Ki-67 Antigen ; MKI67 protein, human ; Fluvastatin (4L066368AS) ; HMGCR protein, human (EC 1.1.1.-) ; Hydroxymethylglutaryl CoA Reductases (EC 1.1.1.-) ; CASP3 protein, human (EC 3.4.22.-) ; Caspase 3 (EC 3.4.22.-)
Language	English
Publishing date	2020-03-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1419277-9
ISSN	1476-5608 ; 1365-7852
ISSN (online)	1476-5608
ISSN	1365-7852
DOI	10.1038/s41391-020-0221-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 5277: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Differential integrated stress response and asparagine production drive symbiosis and therapy resistance of pancreatic adenocarcinoma cells.

Halbrook, Christopher J / Thurston, Galloway / Boyer, Seth / Anaraki, Cecily / Jiménez, Jennifer A / McCarthy, Amy / Steele, Nina G / Kerk, Samuel A / Hong, Hanna S / Lin, Lin / Law, Fiona V / Felton, Catherine / Scipioni, Lorenzo / Sajjakulnukit, Peter / Andren, Anthony / Beutel, Alica K / Singh, Rima / Nelson, Barbara S / Van Den Bergh, Fran /

Krall, Abigail S / Mullen, Peter J / Zhang, Li / Batra, Sandeep / Morton, Jennifer P / Stanger, Ben Z / Christofk, Heather R / Digman, Michelle A / Beard, Daniel A / Viale, Andrea / Zhang, Ji / Crawford, Howard C / Pasca di Magliano, Marina / Jorgensen, Claus / Lyssiotis, Costas A

Nature cancer

2022 Volume 3, Issue 11, Page(s) 1386–1403

Abstract: The pancreatic tumor microenvironment drives deregulated nutrient availability. Accordingly, pancreatic cancer cells require metabolic adaptations to survive and proliferate. Pancreatic cancer subtypes have been characterized by transcriptional and ... ...

Abstract	The pancreatic tumor microenvironment drives deregulated nutrient availability. Accordingly, pancreatic cancer cells require metabolic adaptations to survive and proliferate. Pancreatic cancer subtypes have been characterized by transcriptional and functional differences, with subtypes reported to exist within the same tumor. However, it remains unclear if this diversity extends to metabolic programming. Here, using metabolomic profiling and functional interrogation of metabolic dependencies, we identify two distinct metabolic subclasses among neoplastic populations within individual human and mouse tumors. Furthermore, these populations are poised for metabolic cross-talk, and in examining this, we find an unexpected role for asparagine supporting proliferation during limited respiration. Constitutive GCN2 activation permits ATF4 signaling in one subtype, driving excess asparagine production. Asparagine release provides resistance during impaired respiration, enabling symbiosis. Functionally, availability of exogenous asparagine during limited respiration indirectly supports maintenance of aspartate pools, a rate-limiting biosynthetic precursor. Conversely, depletion of extracellular asparagine with PEG-asparaginase sensitizes tumors to mitochondrial targeting with phenformin.
MeSH term(s)	Animals ; Mice ; Humans ; Pancreatic Neoplasms/drug therapy ; Asparagine/metabolism ; Adenocarcinoma/drug therapy ; Symbiosis ; Tumor Microenvironment
Chemical Substances	Asparagine (7006-34-0)
Language	English
Publishing date	2022-11-21
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2662-1347
ISSN (online)	2662-1347
DOI	10.1038/s43018-022-00463-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Effect of short- and long-term treatment with valproate on carnitine homeostasis in humans.

Morand, Réjane / Todesco, Liliane / Donzelli, Massimiliano / Fischer-Barnicol, David / Mullen, Peter J / Krähenbühl, Stephan

Therapeutic drug monitoring

2012 Volume 34, Issue 4, Page(s) 406–414

Abstract: Aims: The aim of this study was to identify the mechanisms of hypocarnitinemia in patients treated with valproate.: Methods: Plasma concentrations and urinary excretion of carnitine, acetylcarnitine, propionylcarnitine, valproylcarnitine, and ... ...

Abstract	Aims: The aim of this study was to identify the mechanisms of hypocarnitinemia in patients treated with valproate. Methods: Plasma concentrations and urinary excretion of carnitine, acetylcarnitine, propionylcarnitine, valproylcarnitine, and butyrobetaine were determined in a patient starting valproate treatment and in 10 patients on long-term valproate treatment. Transport of carnitine and valproylcarnitine by the proximal tubular carnitine transporter OCTN2 was assessed in vitro. Results: In the patient starting valproate, the plasma carnitine and acetylcarnitine levels dropped for 1-3 weeks and had recovered after 3-5 weeks, whereas the plasma levels of propionyl and valproylcarnitine increased steadily over 5 weeks. The renal excretion and excretion fractions (EFs) of carnitine, acetylcarnitine, propionylcarnitine, and butyrobetaine decreased substantially after starting valproate. Compared with controls, patients on long-term valproate treatment had similar plasma levels of carnitine, acetylcarnitine, and propionylcarnitine, whereas valproylcarnitine was found only in patients. Urinary excretion and renal clearance of carnitine, acetylcarnitine, propionylcarnitine, and butyrobetaine were decreased in valproate-treated compared with that in control patients, reaching statistical significance for carnitine. The EFs of carnitine, acetylcarnitine, and propionylcarnitine were <5% of the filtered load in controls and were lower in valproate-treated patients. In contrast, the EF for valproylcarnitine approached 100%, resulting from a low affinity of valproylcarnitine for the carnitine transporter OCTN2 and competition with concomitantly filtered carnitine. Conclusions: The initial drop in plasma carnitine levels of valproate-treated patients is most likely due to impaired carnitine biosynthesis, whereas the recovery of the plasma carnitine levels is explainable by an increased renal expression of OCTN2. Renally excreted valproylcarnitine does not affect renal handling of carnitine in vivo.
MeSH term(s)	Acetylcarnitine/blood ; Acetylcarnitine/urine ; Adult ; Betaine/analogs & derivatives ; Betaine/blood ; Biological Transport/drug effects ; Carnitine/analogs & derivatives ; Carnitine/blood ; Carnitine/urine ; Cell Line ; Drug Administration Schedule ; Female ; HEK293 Cells ; Homeostasis/drug effects ; Humans ; Kidney Tubules, Proximal/drug effects ; Kidney Tubules, Proximal/metabolism ; Organic Cation Transport Proteins/genetics ; Organic Cation Transport Proteins/metabolism ; Solute Carrier Family 22 Member 5 ; Valproic Acid/administration & dosage
Chemical Substances	Organic Cation Transport Proteins ; SLC22A5 protein, human ; Solute Carrier Family 22 Member 5 ; propionylcarnitine (17298-37-2) ; Betaine (3SCV180C9W) ; gamma-butyrobetaine (407-64-7) ; Valproic Acid (614OI1Z5WI) ; Acetylcarnitine (6DH1W9VH8Q) ; valproylcarnitine (95782-09-5) ; Carnitine (S7UI8SM58A)
Language	English
Publishing date	2012-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	424443-6
ISSN	1536-3694 ; 0163-4356
ISSN (online)	1536-3694
ISSN	0163-4356
DOI	10.1097/FTD.0b013e3182608e2f
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1503: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito