• Je něco špatně v tomto záznamu ?

Expression of STAT3 and hypoxia markers in long-term surviving malignant glioma patients

K. Dvorakova, V. Skarkova, B. Vitovcova, J. Soukup, H. Vosmikova, Z. Pleskacova, A. Skarka, MC. Bartos, P. Krupa, P. Kasparova, J. Petera, E. Rudolf

. 2024 ; 24 (1) : 509. [pub] 20240423

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc24014267

Grantová podpora
No. NU20-03-00360 Ministerstvo Zdravotnictví Ceské Republiky
No. NU20-03-00360 Ministerstvo Zdravotnictví Ceské Republiky
No. NU20-03-00360 Ministerstvo Zdravotnictví Ceské Republiky
No. NU20-03-00360 Ministerstvo Zdravotnictví Ceské Republiky
No. NU20-03-00360 Ministerstvo Zdravotnictví Ceské Republiky
No. NU20-03-00360 Ministerstvo Zdravotnictví Ceské Republiky
No. NU20-03-00360 Ministerstvo Zdravotnictví Ceské Republiky
No. NU20-03-00360 Ministerstvo Zdravotnictví Ceské Republiky
No. NU20-03-00360 Ministerstvo Zdravotnictví Ceské Republiky
No. NU20-03-00360 Ministerstvo Zdravotnictví Ceské Republiky
No. NU20-03-00360 Ministerstvo Zdravotnictví Ceské Republiky
No. NU20-03-00360 Ministerstvo Zdravotnictví Ceské Republiky

BACKGROUND: Glioblastoma is a malignant and aggressive type of central nevous system malignancy characterized by many distinct biological features including extensive hypoxia. Hypoxia in glioblatoma associates with complex signaling patterns including activation of several pathways such as MAPK, PI3K-AKT/mTOR and IL-6/JAK/STAT3 with the master regulator HIF-1, which in turn drive particular tumor behaviors determining, in the end, treatment outcomes and patients fate. Thus, the present study was designed to investigate the expression of selected hypoxia related factors including STAT3 in a small set of long-term surviving glioma patients. METHODS: The expression of selected hypoxia related factors including STAT3 was evaluated in a time series of formalin fixed paraffin embedded and cryopreserved glioma samples from repeatedly resected patients. In addition, comparative studies were also conducted on primary glioma cells derived from original patient samples, stabilized glioma cell lines and tumor-xenograft mice model. Obtained data were correlated with clinical findings too. RESULTS: Glioblastoma samples of the analyzed patients displayed heterogeneity in the expression of hypoxia- related and EMT markers with most interesting trend being observed in pSTAT3. This heterogeneity was subsequently confirmed in other employed models (primocultures derived from glioblastoma tissue resections, cryopreserved tumor specimens, stabilized glioblastoma cell line in vitro and in vivo) and concerned, in particular, STAT3 expression which remained stable. In addition, subsequent studies on the role of STAT3 in the context of glioblastoma hypoxia demonstrated opposing effects of its deletion on cell viability as well as the expression of hypoxia and EMT markers. CONCLUSIONS: Our results suport the importance of STAT3 expression and activity in the context of hypoxia in malignant glioblastoma long-term surviving glioma patients while emphasizing heterogeneity of biological outcomes in varying employed tumor models.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc24014267
003      
CZ-PrNML
005      
20240905133913.0
007      
ta
008      
240725s2024 enk f 000 0|eng||
009      
AR
024    7_
$a 10.1186/s12885-024-12221-w $2 doi
035    __
$a (PubMed)38654280
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Dvorakova, Katerina $u Department of Medical Biology and Genetics, Faculty of Medicine in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic
245    10
$a Expression of STAT3 and hypoxia markers in long-term surviving malignant glioma patients / $c K. Dvorakova, V. Skarkova, B. Vitovcova, J. Soukup, H. Vosmikova, Z. Pleskacova, A. Skarka, MC. Bartos, P. Krupa, P. Kasparova, J. Petera, E. Rudolf
520    9_
$a BACKGROUND: Glioblastoma is a malignant and aggressive type of central nevous system malignancy characterized by many distinct biological features including extensive hypoxia. Hypoxia in glioblatoma associates with complex signaling patterns including activation of several pathways such as MAPK, PI3K-AKT/mTOR and IL-6/JAK/STAT3 with the master regulator HIF-1, which in turn drive particular tumor behaviors determining, in the end, treatment outcomes and patients fate. Thus, the present study was designed to investigate the expression of selected hypoxia related factors including STAT3 in a small set of long-term surviving glioma patients. METHODS: The expression of selected hypoxia related factors including STAT3 was evaluated in a time series of formalin fixed paraffin embedded and cryopreserved glioma samples from repeatedly resected patients. In addition, comparative studies were also conducted on primary glioma cells derived from original patient samples, stabilized glioma cell lines and tumor-xenograft mice model. Obtained data were correlated with clinical findings too. RESULTS: Glioblastoma samples of the analyzed patients displayed heterogeneity in the expression of hypoxia- related and EMT markers with most interesting trend being observed in pSTAT3. This heterogeneity was subsequently confirmed in other employed models (primocultures derived from glioblastoma tissue resections, cryopreserved tumor specimens, stabilized glioblastoma cell line in vitro and in vivo) and concerned, in particular, STAT3 expression which remained stable. In addition, subsequent studies on the role of STAT3 in the context of glioblastoma hypoxia demonstrated opposing effects of its deletion on cell viability as well as the expression of hypoxia and EMT markers. CONCLUSIONS: Our results suport the importance of STAT3 expression and activity in the context of hypoxia in malignant glioblastoma long-term surviving glioma patients while emphasizing heterogeneity of biological outcomes in varying employed tumor models.
650    12
$a transkripční faktor STAT3 $x metabolismus $7 D050796
650    _2
$a lidé $7 D006801
650    _2
$a zvířata $7 D000818
650    _2
$a myši $7 D051379
650    12
$a gliom $x metabolismus $x patologie $x genetika $7 D005910
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a nádory mozku $x metabolismus $x patologie $x genetika $7 D001932
650    _2
$a nádorové buněčné linie $7 D045744
650    _2
$a lidé středního věku $7 D008875
650    _2
$a nádorové biomarkery $x metabolismus $7 D014408
650    _2
$a senioři $7 D000368
650    _2
$a dospělí $7 D000328
650    _2
$a glioblastom $x metabolismus $x patologie $x genetika $7 D005909
650    _2
$a regulace genové exprese u nádorů $7 D015972
650    _2
$a hypoxie $x metabolismus $7 D000860
655    _2
$a časopisecké články $7 D016428
700    1_
$a Skarkova, Veronika $u Department of Medical Biology and Genetics, Faculty of Medicine in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic
700    1_
$a Vitovcova, Barbora $u Department of Medical Biology and Genetics, Faculty of Medicine in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic
700    1_
$a Soukup, Jiri $u The Fingerland Department of Pathology, Faculty of Medicine n Hradec Kralove, Charles University, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic $u Department of Pathology, Military University Hospital Prague, Prague, Czech Republic $u Department of Pathology, First Faculty of Medicine, Charles University, General University Hospital in Prague, Prague, Czech Republic
700    1_
$a Vosmikova, Hana $u The Fingerland Department of Pathology, Faculty of Medicine n Hradec Kralove, Charles University, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic
700    1_
$a Pleskacova, Zuzana $u Department of Oncology and Radiotherapy, Faculty of Medicine in Hradec Kralove, Charles University, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic
700    1_
$a Skarka, Adam $u Department of Chemistry, Faculty of Sciences, University of Hradec Kralove, Hradec Kralove, Czech Republic
700    1_
$a Bartos, Michael Christian $u Department of Neurosurgery, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic
700    1_
$a Krupa, Petr $u Department of Neurosurgery, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic
700    1_
$a Kasparova, Petra $u The Fingerland Department of Pathology, Faculty of Medicine n Hradec Kralove, Charles University, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic
700    1_
$a Petera, Jiri $u Department of Oncology and Radiotherapy, Faculty of Medicine in Hradec Kralove, Charles University, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic
700    1_
$a Rudolf, Emil $u Department of Medical Biology and Genetics, Faculty of Medicine in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic. rudolf@lfhk.cuni.cz
773    0_
$w MED00008171 $t BMC cancer $x 1471-2407 $g Roč. 24, č. 1 (2024), s. 509
856    41
$u https://pubmed.ncbi.nlm.nih.gov/38654280 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y - $z 0
990    __
$a 20240725 $b ABA008
991    __
$a 20240905133907 $b ABA008
999    __
$a ok $b bmc $g 2143828 $s 1226133
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2024 $b 24 $c 1 $d 509 $e 20240423 $i 1471-2407 $m BMC cancer $n BMC Cancer $x MED00008171
GRA    __
$a No. NU20-03-00360 $p Ministerstvo Zdravotnictví Ceské Republiky
GRA    __
$a No. NU20-03-00360 $p Ministerstvo Zdravotnictví Ceské Republiky
GRA    __
$a No. NU20-03-00360 $p Ministerstvo Zdravotnictví Ceské Republiky
GRA    __
$a No. NU20-03-00360 $p Ministerstvo Zdravotnictví Ceské Republiky
GRA    __
$a No. NU20-03-00360 $p Ministerstvo Zdravotnictví Ceské Republiky
GRA    __
$a No. NU20-03-00360 $p Ministerstvo Zdravotnictví Ceské Republiky
GRA    __
$a No. NU20-03-00360 $p Ministerstvo Zdravotnictví Ceské Republiky
GRA    __
$a No. NU20-03-00360 $p Ministerstvo Zdravotnictví Ceské Republiky
GRA    __
$a No. NU20-03-00360 $p Ministerstvo Zdravotnictví Ceské Republiky
GRA    __
$a No. NU20-03-00360 $p Ministerstvo Zdravotnictví Ceské Republiky
GRA    __
$a No. NU20-03-00360 $p Ministerstvo Zdravotnictví Ceské Republiky
GRA    __
$a No. NU20-03-00360 $p Ministerstvo Zdravotnictví Ceské Republiky
LZP    __
$a Pubmed-20240725

Najít záznam

Citační ukazatele

Možnosti archivace