Receptor-targeted therapy of human experimental urinary bladder cancers with cytotoxic LH-RH analog AN-152 [AEZS- 108].
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Receptor-targeted therapy of human experimental urinary bladder cancers with cytotoxic LH-RH analog AN-152 [AEZS- 108]. / Szepeshazi, Karoly; Schally, Andrew V; Keller, Gunhild; Block, Norman L; Benten, Daniel; Halmos, Gabor; Szalontay, Luca; Vidaurre, Irving; Jaszberenyi, Miklos; Rick, Ferenc G.
In: ONCOTARGET, Vol. 3, No. 7, 7, 2012, p. 686-699.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Receptor-targeted therapy of human experimental urinary bladder cancers with cytotoxic LH-RH analog AN-152 [AEZS- 108].
AU - Szepeshazi, Karoly
AU - Schally, Andrew V
AU - Keller, Gunhild
AU - Block, Norman L
AU - Benten, Daniel
AU - Halmos, Gabor
AU - Szalontay, Luca
AU - Vidaurre, Irving
AU - Jaszberenyi, Miklos
AU - Rick, Ferenc G
PY - 2012
Y1 - 2012
N2 - Many bladder cancers progress to invasion with poor prognosis; new therapeutic methods are needed. We developed a cytotoxic LH-RH analog, AN-152 (AEZS-108) containing doxorubicin (DOX), for targeted therapy of cancers expressing LHRH receptors. We investigated the expression of LH-RH receptors in clinical bladder cancers and in HT-1376, J82, RT-4 and HT-1197 human bladder cancer lines. The effect of analog, AN-152, on growth of these tumor lines xenografted into nude mice was analyzed. Using molecular and functional assays, we also evaluated the differences between the effects of AN-152, and DOX alone. We demonstrated the expression of LH-RH receptors on 18 clinical bladder cancers by immunohistochemistry and on four human urinary bladder cancer lines HT-1376, J82, RT-4 and HT-1197 by Western blotting and binding assays. AN-152 powerfully inhibited growth of these bladder cancers in nude mice. AN-152 exerted greater effects than DOX and was less toxic. DOX activated strong multidrug resistance mechanisms in RT-4 and HT-1197 cancers, while AN-152 had no or less such effect. PCR assays and in vitro studies revealed differences in the action of AN-152 and DOX on the expression of genes involved in apoptosis. These results suggest that targeted cytotoxic LH-RH analog, AN-152 (AEZS- 108), should be examined for treatment of patients with LH-RH receptor positive invasive bladder cancers.
AB - Many bladder cancers progress to invasion with poor prognosis; new therapeutic methods are needed. We developed a cytotoxic LH-RH analog, AN-152 (AEZS-108) containing doxorubicin (DOX), for targeted therapy of cancers expressing LHRH receptors. We investigated the expression of LH-RH receptors in clinical bladder cancers and in HT-1376, J82, RT-4 and HT-1197 human bladder cancer lines. The effect of analog, AN-152, on growth of these tumor lines xenografted into nude mice was analyzed. Using molecular and functional assays, we also evaluated the differences between the effects of AN-152, and DOX alone. We demonstrated the expression of LH-RH receptors on 18 clinical bladder cancers by immunohistochemistry and on four human urinary bladder cancer lines HT-1376, J82, RT-4 and HT-1197 by Western blotting and binding assays. AN-152 powerfully inhibited growth of these bladder cancers in nude mice. AN-152 exerted greater effects than DOX and was less toxic. DOX activated strong multidrug resistance mechanisms in RT-4 and HT-1197 cancers, while AN-152 had no or less such effect. PCR assays and in vitro studies revealed differences in the action of AN-152 and DOX on the expression of genes involved in apoptosis. These results suggest that targeted cytotoxic LH-RH analog, AN-152 (AEZS- 108), should be examined for treatment of patients with LH-RH receptor positive invasive bladder cancers.
KW - Animals
KW - Humans
KW - Female
KW - Immunohistochemistry
KW - Disease Models, Animal
KW - Mice
KW - Cell Line, Tumor
KW - Cell Growth Processes/drug effects
KW - Antibiotics, Antineoplastic/pharmacology
KW - Mice, Nude
KW - Xenograft Model Antitumor Assays
KW - Doxorubicin/analogs & derivatives/pharmacology
KW - Drug Delivery Systems/methods
KW - Gonadotropin-Releasing Hormone/analogs & derivatives/pharmacology
KW - Receptors, LHRH/metabolism
KW - Urinary Bladder Neoplasms/drug therapy/metabolism/pathology
KW - Animals
KW - Humans
KW - Female
KW - Immunohistochemistry
KW - Disease Models, Animal
KW - Mice
KW - Cell Line, Tumor
KW - Cell Growth Processes/drug effects
KW - Antibiotics, Antineoplastic/pharmacology
KW - Mice, Nude
KW - Xenograft Model Antitumor Assays
KW - Doxorubicin/analogs & derivatives/pharmacology
KW - Drug Delivery Systems/methods
KW - Gonadotropin-Releasing Hormone/analogs & derivatives/pharmacology
KW - Receptors, LHRH/metabolism
KW - Urinary Bladder Neoplasms/drug therapy/metabolism/pathology
M3 - SCORING: Journal article
VL - 3
SP - 686
EP - 699
JO - ONCOTARGET
JF - ONCOTARGET
SN - 1949-2553
IS - 7
M1 - 7
ER -
