Did you know ? If you order before Friday 14h we deliver 90PCT of the the time next Tuesday, GENTAUR another in time delivery

Pubmed ID :30274984
Publication Date : //

Targeting Resistance against the MDM2 Inhibitor RG7388 in Glioblastoma Cells by the MEK Inhibitor Trametinib.


Resistance is an obstacle of glioma therapy. Despite targeted interventions, tumors harbor primary resistance or become resistant over short course of treatment. This study examined the mouse double minute 2 (MDM2) inhibitor RG7388 together with radiotherapy and analyzed strategies to overcome acquired MDM2 inhibitor resistance in glioblastoma. Effects of RG7388 and radiotherapy were analyzed in p53 wild-type glioblastoma cell lines and glioma-initiating cells. RG7388 resistant cells were generated by increasing RG7388 doses over 3 months. Regulated pathways were investigated by microarray, qRT-PCR, and immunoblot analysis and specifically inhibited to evaluate rational salvage therapies at RG7388 resistance. Effects of RG7388 and trametinib treatment were challenged in an orthotopical mouse model with RG7388 resistant U87MG glioblastoma cells. MDM2 inhibition required functional p53 and showed synergistic activity with radiotherapy in first-line treatment. Long-term exposure to RG7388 induced resistance by activation of the extracellular signal-regulated kinases 1/2 (ERK1/2)-insulin growth factor binding protein 1 (IGFBP1) signaling cascade, which was specifically overcome by ERK1/2 pathway inhibition with trametinib and knockdown of IGFBP1. Combining trametinib with continued RG7388 treatment enhanced antitumor effects at RG7388 resistance and These data provide a rationale for combining RG7388 and radiotherapy as first-line therapy with a specific relevance for tumors insensitive to alkylating standard chemotherapy and for the addition of trametinib to continued RG7388 treatment as salvage therapy after acquired resistance against RG7388 for clinical practice.

Authors : Berberich Anne , Kessler Tobias , Thomé Carina M , Pusch Stefan , Hielscher Thomas , Sahm Felix , Oezen Iris , Schmitt Lara-Marie , Ciprut Sara , Hucke Nanina , Ruebmann Petra , Fischer Manuel , Lemke Dieter , Breckwoldt Michael O , von Deimling Andreas , Bendszus Martin , Platten Michael , Wick Wolfgang ,

Related products :

Catalog number Product name Quantity
orb60526 Tie2 kinase inhibitor Tie2 kinase inhibitor is a potent, reversible, and ATP-binding site-targeting Tie2 inhibitor with an IC50 of 250 nM. For research use only. 10 mg
A-1083 GSK-1120212 (Trametinib), MEK inhibitor 20 mg
A-1083 GSK-1120212 (Trametinib), MEK inhibitor 10 mg
A-1083 GSK-1120212 (Trametinib), MEK inhibitor 1000 mg
A-1083 GSK-1120212 (Trametinib), MEK inhibitor 50 mg
A-1083 GSK-1120212 (Trametinib), MEK inhibitor 200 mg
A-1083 GSK-1120212 (Trametinib), MEK inhibitor 100 mg
A-1083 GSK-1120212 (Trametinib), MEK inhibitor 5 mg
A-1083 GSK-1120212 (Trametinib) Mechanisms: MEK inhibitor 100mg
A-1083 GSK-1120212 (Trametinib) Mechanisms: MEK inhibitor 20mg
A-1083 GSK-1120212 (Trametinib) Mechanisms: MEK inhibitor 50mg
A-1083 GSK-1120212 (Trametinib) Mechanisms: MEK inhibitor 10mg
A-1083 GSK-1120212 (Trametinib) Mechanisms: MEK inhibitor 5mg
10-664-50023 Metalloproteinase inhibitor 1 - TIMP-1; Erythroid potentiating activity; EPA; Tissue inhibitor of metalloproteinases; Fibroblast collagenase inhibitor; Collagenase inhibitor N_A 0.05 mg
EIAAB43424 IkappaBR,I-kappa-B-related protein,Ikbr,Inhibitor of kappa B-related protein,NF-kappa-B inhibitor-like protein 2,Nfkbil2,Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-li
U1312h CLIA ALP,Antileukoproteinase,BLPI,Homo sapiens,Human,HUSI-1,MPI,Mucus proteinase inhibitor,Protease inhibitor WAP4,Secretory leukocyte protease inhibitor,Seminal proteinase inhibitor,SLPI,WAP four-dis 96T
E1312h ELISA ALP,Antileukoproteinase,BLPI,Homo sapiens,Human,HUSI-1,MPI,Mucus proteinase inhibitor,Protease inhibitor WAP4,Secretory leukocyte protease inhibitor,Seminal proteinase inhibitor,SLPI,WAP four-di 96T
E1312h ELISA kit ALP,Antileukoproteinase,BLPI,Homo sapiens,Human,HUSI-1,MPI,Mucus proteinase inhibitor,Protease inhibitor WAP4,Secretory leukocyte protease inhibitor,Seminal proteinase inhibitor,SLPI,WAP fo 96T
E0552h ELISA kit CLGI,Collagenase inhibitor,EPA,Erythroid-potentiating activity,Fibroblast collagenase inhibitor,Homo sapiens,Human,Metalloproteinase inhibitor 1,TIMP,TIMP1,TIMP-1,Tissue inhibitor of metall 96T
E0552h ELISA CLGI,Collagenase inhibitor,EPA,Erythroid-potentiating activity,Fibroblast collagenase inhibitor,Homo sapiens,Human,Metalloproteinase inhibitor 1,TIMP,TIMP1,TIMP-1,Tissue inhibitor of metalloprot 96T
U0552h CLIA CLGI,Collagenase inhibitor,EPA,Erythroid-potentiating activity,Fibroblast collagenase inhibitor,Homo sapiens,Human,Metalloproteinase inhibitor 1,TIMP,TIMP1,TIMP-1,Tissue inhibitor of metalloprote 96T
U0128b CLIA Bos taurus,Bovine,Collagenase inhibitor,Metalloproteinase inhibitor 2,TIMP2,TIMP-2,Tissue inhibitor of metalloproteinases 2 96T
E0128b ELISA Bos taurus,Bovine,Collagenase inhibitor,Metalloproteinase inhibitor 2,TIMP2,TIMP-2,Tissue inhibitor of metalloproteinases 2 96T
E0128b ELISA kit Bos taurus,Bovine,Collagenase inhibitor,Metalloproteinase inhibitor 2,TIMP2,TIMP-2,Tissue inhibitor of metalloproteinases 2 96T
U1444h CLIA Homo sapiens,Human,Placental ribonuclease inhibitor,Placental RNase inhibitor,PRI,RAI,Ribonuclease inhibitor,Ribonuclease_angiogenin inhibitor 1,RNH,RNH1 96T


 

GENTAUR Belgium BVBA BE0473327336
Voortstraat 49, 1910 Kampenhout BELGIUM
Tel 0032 16 58 90 45

Fax 0032 16 50 90 45
info@gentaur.com | Gentaur | Gentaur





GENTAUR Ltd.
Unicorn House, Station Cl
Hertfordshire, Potters Bar EN6 1TL
Whetstone London N20 9BH
Tel 020 3393 8531 Fax 020 8445 9411
uk@gentaur.com | Gentaur | Gentaur

 

 




GENTAUR France SARL
9, rue Lagrange, 75005 Paris
Tel 01 43 25 01 50

Fax 01 43 25 01 60
RCS Paris B 484 237 888

SIRET 48423788800017
RIB 30004 00187 00010092253 10
BNP PARIBAS PARIS PL MAUBERT BIC BNPAFRPPPRG
IBAN FR76 3000 4001 8700 0100 9225 310
france@gentaur.com | Gentaur | Gentaur

GENTAUR GmbH
Marienbongard 20
52062 Aachen Deutschland
Support Karolina Elandt
Tel: 0035929830070
Fax: (+49) 241 56 00 47 88

Logistic :0241 40 08 90 86
Bankleitzahl 39050000
IBAN lautet DE8839050000107569353
Handelsregister Aachen HR B 16058
Umsatzsteuer-Identifikationsnummer *** DE 815175831
Steuernummer 201/5961/3925
de@gentaur.com | Gentaur | Gentaur

GENTAUR U.S.A
Genprice Inc, Logistics
547, Yurok Circle
San Jose, CA 95123
CA 95123
Tel (408) 780-0908,
Fax (408) 780-0908,
sales@genprice.com

Genprice Inc, Invoices and accounting
6017 Snell Ave, Ste 357
San Jose, CA 95123




GENTAUR Nederland BV
NL850396268B01 KVK nummer 52327027
Kuiper 1
5521 DG Eersel Nederland
Tel:  0208-080893  Fax: 0497-517897
nl@gentaur.com | Gentaur | Gentaur
IBAN: NL04 RABO 0156 9854 62   SWIFT RABONL2U






GENTAUR Spain
tel:0911876558
spain@gentaur.com | Gentaur | Gentaur






ГЕНТАУЪР БЪЛГАРИЯ
ID # 201 358 931 /BULSTAT
София 1000, ул. "Граф Игнатиев" 53 вх. В, ет. 2
Tel 0035924682280 Fax 0035924808322
e-mail: Sofia@gentaur.com | Gentaur | Gentaur
IBAN: BG11FINV91501014771636
BIC: FINVBGSF

GENTAUR Poland Sp. z o.o.


ul. Grunwaldzka 88/A m.2
81-771 Sopot, Poland
TEL Gdansk 058 710 33 44 FAX  058 710 33 48              

poland@gentaur.com | Gentaur | Gentaur

Other countries

Österreich +43720880899

Canada Montreal +15149077481

Ceská republika Praha +420246019719

Danmark +4569918806

Finland Helsset +358942419041

Magyarország Budapest +3619980547

Ireland Dublin+35316526556

Luxembourg+35220880274

Norge Oslo+4721031366

Sverige Stockholm+46852503438

Schweiz Züri+41435006251

US New York+17185132983

GENTAUR Italy
SRL IVA IT03841300167
Piazza Giacomo Matteotti, 6
24122 Bergamo Tel 02 36 00 65 93
Fax 02 36 00 65 94
italia@gentaur.com | Gentaur | Gentaur