The new platinum anticancer agent LA-12 induces Retinol
Bionding Protein 4 in vivo

a 2011

The new platinum anticancer agent LA-12 induces Retinol Bionding Protein 4 in vivo

STRUHÁROVÁ, Iva, Pavel BOUCHAL, Jiří JARKOVSKÝ, Kristýna HRAZDILOVÁ, Monika DVOŘÁKOVÁ et. al.

Basic information

Original name

The new platinum anticancer agent LA-12 induces Retinol Bionding Protein 4 in vivo

Authors

STRUHÁROVÁ, Iva, Pavel BOUCHAL, Jiří JARKOVSKÝ, Kristýna HRAZDILOVÁ, Monika DVOŘÁKOVÁ, Lenka HERNYCHOVÁ, Jiří DAMBORSKÝ, Petr SOVA and Bořivoj VOJTĚŠEK

Edition

5th European Summer School in "Proteomics Basics" 2011

Other information

Language

English

Type of outcome

Konferenční abstrakt

Field of Study

10600 1.6 Biological sciences

Country of publisher

Italy

Confidentiality degree

není předmětem státního či obchodního tajemství

Organization unit

Faculty of Science

Keywords in English

proteomics, retinol binding protein 4, RBP4, LA-12

Abstract

V originále

The initial pharmacokinetic study of a new anticancer agent (OC-6-43)-bis(acetato)(1-adamantylamine)amminedichloroplatinum (IV) (LA-12) was complemented by proteomic screening of rat plasma. The objective of the study was to identify new LA-12 target proteins which could potentially serve as markers of LA-12 treatment, response and therapy monitoring. Proteomic profiles were measured by surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF MS) for 72 samples of rat plasma randomized according to LA-12 dose and time from administration. Correlation of 92 peak clusters with platinum concentration was evaluated using Spearman correlation analysis. We identified plasma retinol binding protein RBP4 as a protein correlating with LA-12 level in both rat plasma and plasma ultrafiltrate. Similar trend was observed for randomly selected patients involved in Phase I of clinical trials. RBP4 induction is in agreement with known RBP4 regulation by amantadine and cisplatin. Since retinol metabolism is disrupted in many cancers and inversely associates with malignancy, these data identify a potential novel mechanism for the action of LA-12 and other similar anti-cancer drugs.

Links

GAP304/10/0868, research and development project

Name: Studium molekulárních mechanismů časného metastazování do lymfatických uzlin u karcinomu prsu nízkého stupně malignity pomocí proteomických technik

Investor: Czech Science Foundation

MSM0021622413, plan (intention)

Name: Proteiny v metabolismu a při interakci organismů s prostředím

Investor: Ministry of Education, Youth and Sports of the CR, Proteins in metabolism and interaction of organisms with the environment

MZ0MOU2005, plan (intention)

Name: Funkční diagnostika zhoubných nádorů

Citovat

STRUHÁROVÁ, Iva, Pavel BOUCHAL, Jiří JARKOVSKÝ, Kristýna HRAZDILOVÁ, Monika DVOŘÁKOVÁ, Lenka HERNYCHOVÁ, Jiří DAMBORSKÝ, Petr SOVA and Bořivoj VOJTĚŠEK. The new platinum anticancer agent LA-12 induces Retinol Bionding Protein 4 in vivo. In 5th European Summer School in "Proteomics Basics". 2011.

@proceedings{960197,
   author = {Struhárová, Iva and Bouchal, Pavel and Jarkovský, Jiří and Hrazdilová, Kristýna and Dvořáková, Monika and Hernychová, Lenka and Damborský, Jiří and Sova, Petr and Vojtěšek, Bořivoj},
   booktitle = {5th European Summer School in "Proteomics Basics"},
   keywords = {proteomics, retinol binding protein 4, RBP4, LA-12},
   language = {eng},
   title = {The new platinum anticancer agent LA-12 induces Retinol Bionding Protein 4 in vivo},
   year = {2011}
}

TY  - CONF
ID  - 960197
AU  - Struhárová, Iva - Bouchal, Pavel - Jarkovský, Jiří - Hrazdilová, Kristýna - Dvořáková, Monika - Hernychová, Lenka - Damborský, Jiří - Sova, Petr - Vojtěšek, Bořivoj
PY  - 2011
TI  - The new platinum anticancer agent LA-12 induces Retinol Bionding Protein 4 in vivo
KW  - proteomics, retinol binding protein 4, RBP4, LA-12
N2  - The initial pharmacokinetic study of a new anticancer agent (OC-6-43)-bis(acetato)(1-adamantylamine)amminedichloroplatinum (IV) (LA-12) was complemented by proteomic screening of rat plasma. The objective of the study was to identify new LA-12 target proteins which could potentially serve as markers of LA-12 treatment, response and therapy monitoring. Proteomic profiles were measured by surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF MS) for 72 samples of rat plasma randomized according to LA-12 dose and time from administration. Correlation of 92 peak clusters with platinum concentration was evaluated using Spearman correlation analysis. We identified plasma retinol binding protein RBP4 as a protein correlating with LA-12 level in both rat plasma and plasma ultrafiltrate. Similar trend was observed for randomly selected patients involved in Phase I of clinical trials. RBP4 induction is in agreement with known RBP4 regulation by amantadine and cisplatin. Since retinol metabolism is disrupted in many cancers and inversely associates with malignancy, these data identify a potential novel mechanism for the action of LA-12 and other similar anti-cancer drugs.
ER  -

STRUHÁROVÁ, Iva, Pavel BOUCHAL, Jiří JARKOVSKÝ, Kristýna HRAZDILOVÁ, Monika DVOŘÁKOVÁ, Lenka HERNYCHOVÁ, Jiří DAMBORSKÝ, Petr SOVA and Bořivoj VOJTĚŠEK. The new platinum anticancer agent LA-12 induces Retinol Bionding Protein 4 in vivo. In \textit{5th European Summer School in ''Proteomics Basics''}. 2011.

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