Targeting mTOR: prospects for mTOR complex 2 inhibitors in cancer therapy (Q24632296)

The target of rapamycin complex 2 controls dendritic tiling of Drosophila sensory neurons through the Tricornered kinase signalling pathway

Europe PubMed Central

title

Targeting mTOR: prospects for mTOR complex 2 inhibitors in cancer therapy (English)

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author name string

C A Sparks

series ordinal

1

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D A Guertin

series ordinal

2

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language of work or name

English

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publication date

1 July 2010

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published in

Oncogene

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volume

29

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issue

26

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page(s)

3733-44

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cites work

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Targeting tumorigenesis: development and use of mTOR inhibitors in cancer therapy

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Characterization of Rictor phosphorylation sites reveals direct regulation of mTOR complex 2 by S6K1

7 April 2017

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DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival

7 April 2017

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Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2

7 April 2017

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mTOR complex 2 is required for the development of prostate cancer induced by Pten loss in mice

7 April 2017

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mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1)

7 April 2017

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Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling

7 April 2017

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The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1

7 April 2017

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The TSC1-TSC2 complex: a molecular switchboard controlling cell growth

7 April 2017

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AKT/PKB signaling: navigating downstream

7 April 2017

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Identification of Protor as a novel Rictor-binding component of mTOR complex-2

7 April 2017

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Human Sin1 contains Ras-binding and pleckstrin homology domains and suppresses Ras signalling

7 April 2017

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Identification of Sin1 as an essential TORC2 component required for complex formation and kinase activity

7 April 2017

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Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex

7 April 2017

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Disruption of the mouse mTOR gene leads to early postimplantation lethality and prohibits embryonic stem cell development

7 April 2017

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Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive

7 April 2017

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Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton

7 April 2017

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mTOR is essential for growth and proliferation in early mouse embryos and embryonic stem cells

7 April 2017

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Crystal structure of an activated Akt/protein kinase B ternary complex with GSK3-peptide and AMP-PNP

7 April 2017

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Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control

7 April 2017

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Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action

7 April 2017

1 reference

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mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery

7 April 2017

1 reference

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Mechanism of activation of protein kinase B by insulin and IGF-1

7 April 2017

1 reference

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Rictor/TORC2 regulates Caenorhabditis elegans fat storage, body size, and development through sgk-1

7 April 2017

1 reference

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Molecular mechanism for the regulation of protein kinase B/Akt by hydrophobic motif phosphorylation

7 April 2017

1 reference

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Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers

7 April 2017

1 reference

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TOR signaling in growth and metabolism

7 April 2017

1 reference

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TORC2 plasma membrane localization is essential for cell viability and restricted to a distinct domain

7 April 2017

1 reference

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TOR1 and TOR2 have distinct locations in live cells

7 April 2017

1 reference

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Tor2 directly phosphorylates the AGC kinase Ypk2 to regulate actin polarization

7 April 2017

1 reference

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Molecular organization of target of rapamycin complex 2.

7 April 2017

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The pleckstrin homology domain proteins Slm1 and Slm2 are required for actin cytoskeleton organization in yeast and bind phosphatidylinositol-4,5-bisphosphate and TORC2.

7 April 2017

1 reference

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Genome-wide lethality screen identifies new PI4,5P2 effectors that regulate the actin cytoskeleton.

7 April 2017

1 reference

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GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR

7 April 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031870

Defining the role of mTOR in cancer

7 April 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031870

Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1

7 April 2017

1 reference

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Multiallelic disruption of the rictor gene in mice reveals that mTOR complex 2 is essential for fetal growth and viability

7 April 2017

1 reference

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SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity

7 April 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031870

mSin1 is necessary for Akt/PKB phosphorylation, and its isoforms define three distinct mTORC2s

7 April 2017

1 reference

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Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB

7 April 2017

1 reference

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TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function

7 April 2017

1 reference

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The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif

7 April 2017

1 reference

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The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C

7 April 2017

1 reference

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mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt

7 April 2017

1 reference

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mTOR signaling at a glance

7 April 2017

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Targeting the phosphoinositide 3-kinase pathway in cancer

7 April 2017

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An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1

7 April 2017

1 reference

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Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer

7 April 2017

1 reference

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Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor

7 April 2017

1 reference

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mTORC1-activated S6K1 phosphorylates Rictor on threonine 1135 and regulates mTORC2 signaling

27 September 2017

1 reference

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An emerging role of mTOR in lipid biosynthesis.

27 September 2017

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mTOR and cancer: many loops in one pathway.

27 September 2017

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Rictor is a novel target of p70 S6 kinase-1.

27 September 2017

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Targeted inhibition of mammalian target of rapamycin signaling inhibits tumorigenesis of colorectal cancer

27 September 2017

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Targeting mTOR globally in cancer: thinking beyond rapamycin

27 September 2017

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The double-edged sword of autophagy modulation in cancer

27 September 2017

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Signaling events downstream of mammalian target of rapamycin complex 2 are attenuated in cells and tumors deficient for the tuberous sclerosis complex tumor suppressors

27 September 2017

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Biochemical, cellular, and in vivo activity of novel ATP-competitive and selective inhibitors of the mammalian target of rapamycin

27 September 2017

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AKT-independent signaling downstream of oncogenic PIK3CA mutations in human cancer

27 September 2017

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mTOR complex 2 in adipose tissue negatively controls whole-body growth

27 September 2017

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Site-specific mTOR phosphorylation promotes mTORC1-mediated signaling and cell growth.

27 September 2017

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Nutrient control of TORC1, a cell-cycle regulator

27 September 2017

1 reference

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Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR)

27 September 2017

1 reference

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PIKKing on PKB: regulation of PKB activity by phosphorylation

27 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031870

Rictor/TORC2 regulates fat metabolism, feeding, growth, and life span in Caenorhabditis elegans

27 September 2017

1 reference

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Differential requirement of mTOR in postmitotic tissues and tumorigenesis

27 September 2017

1 reference

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Skeletal muscle-specific ablation of raptor, but not of rictor, causes metabolic changes and results in muscle dystrophy

27 September 2017

1 reference

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TOR complex 2 is needed for cell cycle progression and anchorage-independent growth of MCF7 and PC3 tumor cells

27 September 2017

1 reference

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Rapamycin inhibits trypanosome cell growth by preventing TOR complex 2 formation

27 September 2017

1 reference

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PIP3-independent activation of TorC2 and PKB at the cell's leading edge mediates chemotaxis

27 September 2017

1 reference

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A new pharmacologic action of CCI-779 involves FKBP12-independent inhibition of mTOR kinase activity and profound repression of global protein synthesis

27 September 2017

1 reference

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The TSC1-TSC2 complex is required for proper activation of mTOR complex 2

27 September 2017

1 reference

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Regulation of ceramide biosynthesis by TOR complex 2.

27 September 2017

1 reference

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TOR regulation of AGC kinases in yeast and mammals

27 September 2017

1 reference

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mTORC2 activity is elevated in gliomas and promotes growth and cell motility via overexpression of rictor

27 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031870

PRAS40 and PRR5-like protein are new mTOR interactors that regulate apoptosis.

27 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031870

Muscle-specific deletion of rictor impairs insulin-stimulated glucose transport and enhances Basal glycogen synthase activity

27 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031870

Rapamycin regulates the phosphorylation of rictor

27 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031870

Classical PKC isoforms in cancer

27 September 2017

1 reference

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PDGFRs are critical for PI3K/Akt activation and negatively regulated by mTOR

27 September 2017

1 reference

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Rapamycin derivatives reduce mTORC2 signaling and inhibit AKT activation in AML.

27 September 2017

1 reference

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Inhibition of the phosphatidylinositol 3-kinase/mammalian target of rapamycin pathway in hematologic malignancies.

27 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031870

The phosphatidylinositol 4,5-biphosphate and TORC2 binding proteins Slm1 and Slm2 function in sphingolipid regulation

27 September 2017

1 reference

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TSC1/TSC2 and Rheb have different effects on TORC1 and TORC2 activity

27 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031870

Serum and glucocorticoid-regulated protein kinases: variations on a theme

27 September 2017

1 reference

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Drosophila target of rapamycin kinase functions as a multimer.

27 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031870

mTOR, a new therapeutic target in acute myeloid leukemia

27 September 2017

1 reference

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TOR complex 2 integrates cell movement during chemotaxis and signal relay in Dictyostelium

27 September 2017

1 reference

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Phase II trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell lymphoma

27 September 2017

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The human stress-activated protein kinase-interacting 1 gene encodes JNK-binding proteins

27 September 2017

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The in vivo role of PtdIns(3,4,5)P3 binding to PDK1 PH domain defined by knockin mutation

27 September 2017

1 reference

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Identification of a conserved motif required for mTOR signaling

27 September 2017

1 reference

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A novel Ras-interacting protein required for chemotaxis and cyclic adenosine monophosphate signal relay in Dictyostelium

27 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031870

AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity

27 September 2017

1 reference

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Re-evaluating AKT regulation: role of TOR complex 2 in tissue growth

30 May 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031870

Pathological angiogenesis is induced by sustained Akt signaling and inhibited by rapamycin.

30 May 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031870

The pharmacology of mTOR inhibition

30 May 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031870

RAG GTPases in nutrient-mediated TOR signaling pathway

28 November 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031870

TORC-specific phosphorylation of mammalian target of rapamycin (mTOR): phospho-Ser2481 is a marker for intact mTOR signaling complex 2.

28 November 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031870

Rapamycin sensitivity of the Schizosaccharomyces pombe tor2 mutant and organization of two highly phosphorylated TOR complexes by specific and common subunits

28 November 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031870

PRR5, a novel component of mTOR complex 2, regulates platelet-derived growth factor receptor beta expression and signaling.

28 November 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031870

mTOR.RICTOR is the Ser473 kinase for Akt/protein kinase B in 3T3-L1 adipocytes

28 November 2018

1 reference

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28 November 2018

Identifiers

DOI

10.1038/ONC.2010.139

1 reference

Dimensions Publication ID

840856

1051644324

0 references

840856

1 reference

1 reference

1 reference