Role of Survivin and Akt in Diffuse Large B-cell Lymphoma.
Pilot study.

J 2007

Role of Survivin and Akt in Diffuse Large B-cell Lymphoma. Pilot study.

SVOBODA, Marek, Pavel FABIAN, Ingrid VÁŠOVÁ, Lenka RADOVÁ, Jitka BERKOVCOVÁ et. al.

Basic information

Original name

Role of Survivin and Akt in Diffuse Large B-cell Lymphoma. Pilot study.

Name in Czech

Význam survivinu a Akt u difúzního velkobuněčného B-lymfomu. Pilotní studie.

Authors

SVOBODA, Marek, Pavel FABIAN, Ingrid VÁŠOVÁ, Lenka RADOVÁ, Jitka BERKOVCOVÁ, Martin KLABUSAY, Rudolf NENUTIL and Aleš REJTHAR

Edition

American Association for Cancer Research Annual Meeting Proceedings, 2007 Apr 14-18; Los Angeles, CA. Philadelphia (PA): AACR; 2007, Philadelphia, PA, USA, American Association for Cancer Research, 2007, 0197-016X

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30200 3.2 Clinical medicine

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Organization unit

Faculty of Medicine

Keywords in English

Lymphoma;prognosis;prediction; Akt kinase; survivin protein

Abstract

ORIG CZ

V originále

Deregulation of apoptosis plays an important role in normal and malignant lymphopoesis. Survivin is a member of the inhibitor of apoptosis (IAP) family and Akt (protein kinase B) is a serine/threonine kinase involved in the regulation of cell survival signals. But their role in diffuse large B-cell lymphoma (DLBCL) has not been fully elucidated. On the other hand, both molecules and their signaling pathways are targeted by new investigational antineoplastic agents. We studied 46 adult patients with de novo DLBCL.The patients consisted of 29 men and 27 women with a median age of 59 years (range, 24-79). Advanced stage (III/IV) was observed in 24 cases (52%) and the distribution according to the IPI was as follows: low risk, 20 cases (44%); low/intermediate risk, 12 (26%); high/intermediate risk 9 (19%); and high risk, 5 (11%). All patients were treated with curative intent and except one case, an initial treatment started with a chemotherapy regimen CHOP (cyclophosphamide, doxorubicine, vincristine and prednison) with a median of 6 administrated cycles of chemotherapy. Overall response rate was 69% with a complete response (CR) in 31 patients (67%). Patients were also divided into two groups: those with cured disease (31 cases, 54%) and those with fatal course of disease (21 cases, 46%). The median follow-up of the surviving patients was 4,3 years and patients who died from progression of DLBCL was 9 months. Imunohistochemistry was performed on paraffin-embdded tissue sections with a monoclonal antibodies against: Survivin, Akt-1, Akt-2, phospho-Akt-Ser-473 and phospho-Akt-Thr-307. Except survivin, the expression was considered positive if 5% or more of the tumor cells were stained with the antibody, in the case of survivin the cut-off was 20% of positive tumor cells. The Kaplan-Meier method was used to estimate overall (OS) and relaps-free survival (RFS). P-value was based on Gehan-Wilcoxons test or chi-square test and P-values < 0,05 were considered significant. Tumor expression of Survivin and phosphorylated Akt-2 on Ser-473 correlated with an inferior OS and RFS and predicted outcome in patients with DLBCL. Thus, patients with positive expression of Akt-2 phosphorylated on Ser-473 had a median of OS and RFS lower compared to those who were p-Akt-Ser-473 negative (OS: 42 months vs 14 months, p<0,008; RFS: 37 months vs 9 months, p<0,004 ). Similar data were obtained for Survivin (OS: 40 months vs 29 months, p=0,1; RFS: 40 months vs 15 months, p<0,035). All other results were not statistical significant. The results support the proposed key role of Survivin and Akt-2 in regulation of apoptosis with direct impact on clinical outcome of patients with DLBCL.Both molecules are potential targets for therapeutic intervention in DLBCL. Acknowledgment: This project was supported by Internal Grant Agency, Ministry of Health, Czech Republic. No.: NR/8335-3.

In Czech

Práce pouze v anglickém jazyce.

Links

NR8335, research and development project

Name: Predikce chemosenzitivity / chemorezistence na cílenou protinádorovou terapii u pacientek s karcinomem prsu s prokázanou HER-2 pozitivitou, na podkladě analýzy Akt signální dráhy a sérové hladiny HER-2 receptoru

Citovat

SVOBODA, Marek, Pavel FABIAN, Ingrid VÁŠOVÁ, Lenka RADOVÁ, Jitka BERKOVCOVÁ, Martin KLABUSAY, Rudolf NENUTIL and Aleš REJTHAR. Role of Survivin and Akt in Diffuse Large B-cell Lymphoma. Pilot study. American Association for Cancer Research Annual Meeting Proceedings, 2007 Apr 14-18; Los Angeles, CA. Philadelphia (PA): AACR; 2007. Philadelphia, PA, USA: American Association for Cancer Research, 2007, vol. 2007, No 48, p. 42. ISSN 0197-016X.

@article{725508,
   author = {Svoboda, Marek and Fabian, Pavel and Vášová, Ingrid and Radová, Lenka and Berkovcová, Jitka and Klabusay, Martin and Nenutil, Rudolf and Rejthar, Aleš},
   article_location = {Philadelphia, PA, USA},
   article_number = {48},
   keywords = {Lymphoma;prognosis;prediction; Akt kinase; survivin protein},
   language = {eng},
   issn = {0197-016X},
   journal = {American Association for Cancer Research Annual Meeting Proceedings, 2007 Apr 14-18; Los Angeles, CA. Philadelphia (PA): AACR; 2007},
   title = {Role of Survivin and Akt in Diffuse Large B-cell Lymphoma. Pilot study.},
   volume = {2007},
   year = {2007}
}

TY  - JOUR
ID  - 725508
AU  - Svoboda, Marek - Fabian, Pavel - Vášová, Ingrid - Radová, Lenka - Berkovcová, Jitka - Klabusay, Martin - Nenutil, Rudolf - Rejthar, Aleš
PY  - 2007
TI  - Role of Survivin and Akt in Diffuse Large B-cell Lymphoma. Pilot study.
JF  - American Association for Cancer Research Annual Meeting Proceedings, 2007 Apr 14-18; Los Angeles, CA. Philadelphia (PA): AACR; 2007
VL  - 2007
IS  - 48
SP  - 42
EP  - 42
PB  - American Association for Cancer Research
SN  - 0197016X
KW  - Lymphoma;prognosis;prediction
KW  - Akt kinase
KW  - survivin protein
N2  - Deregulation of apoptosis plays an important role in normal and malignant lymphopoesis. Survivin is a member of the inhibitor of apoptosis (IAP) family and Akt (protein kinase B) is a serine/threonine kinase involved in the regulation of cell survival signals. But their role in diffuse large B-cell lymphoma (DLBCL) has not been fully elucidated. On the other hand, both molecules and their signaling pathways are targeted by new investigational antineoplastic agents. We studied 46 adult patients with de novo DLBCL.The patients consisted of 29 men and 27 women with a median age of 59 years (range, 24-79). Advanced stage (III/IV) was observed in 24 cases (52%) and the distribution according to the IPI was as follows: low risk, 20 cases (44%); low/intermediate risk, 12 (26%); high/intermediate risk 9 (19%); and high risk, 5 (11%). All patients were treated with curative intent and except one case, an initial treatment started with a chemotherapy regimen CHOP (cyclophosphamide, doxorubicine, vincristine and prednison) with a median of 6 administrated cycles of chemotherapy. Overall response rate was 69% with a complete response (CR) in 31 patients (67%). Patients were also divided into two groups: those with cured disease (31 cases, 54%) and those with fatal course of disease (21 cases, 46%). The median follow-up of the surviving patients was 4,3 years and patients who died from progression of DLBCL was 9 months. Imunohistochemistry was performed on paraffin-embdded tissue sections with a monoclonal antibodies against: Survivin, Akt-1, Akt-2, phospho-Akt-Ser-473 and phospho-Akt-Thr-307. Except survivin, the expression was considered positive if 5% or more of the tumor cells were stained with the antibody, in the case of survivin the cut-off was 20% of positive tumor cells. The Kaplan-Meier method was used to estimate overall (OS) and relaps-free survival (RFS). P-value was based on Gehan-Wilcoxons test or chi-square test and P-values < 0,05 were considered significant. Tumor expression of Survivin and phosphorylated Akt-2 on Ser-473 correlated with an inferior OS and RFS and predicted outcome in patients with DLBCL. Thus, patients with positive expression of Akt-2 phosphorylated on Ser-473 had a median of OS and RFS lower compared to those who were p-Akt-Ser-473 negative (OS: 42 months vs 14 months, p<0,008; RFS: 37 months vs 9 months, p<0,004 ). Similar data were obtained for Survivin (OS: 40 months vs 29 months, p=0,1; RFS: 40 months vs 15 months, p<0,035). All other results were not statistical significant. The results support the proposed key role of Survivin and Akt-2 in regulation of apoptosis with direct impact on clinical outcome of patients with DLBCL.Both molecules are potential targets for therapeutic intervention in DLBCL. Acknowledgment: This project was supported by Internal Grant Agency, Ministry of Health, Czech Republic. No.: NR/8335-3.
ER  -

SVOBODA, Marek, Pavel FABIAN, Ingrid VÁŠOVÁ, Lenka RADOVÁ, Jitka BERKOVCOVÁ, Martin KLABUSAY, Rudolf NENUTIL and Aleš REJTHAR. Role of Survivin and Akt in Diffuse Large B-cell Lymphoma. Pilot study. \textit{American Association for Cancer Research Annual Meeting Proceedings, 2007 Apr 14-18; Los Angeles, CA. Philadelphia (PA): AACR; 2007}. Philadelphia, PA, USA: American Association for Cancer Research, 2007, vol.~2007, No~48, p.~42. ISSN~0197-016X.

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