Continuous administration of the somatostatin structural derivative /TT-232/ by subcutaneously implanted osmotic pump improves the efficacy and potency of antitumor therapy in different mouse and human tumor models

Miguel Tejeda, D. Gaál, L. Hullán, O. Csuka, R. Schwab, O. Szokoloczi, G. Kéri

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: The somatostatin structural derivative, TT-232, has a special 5-residue ring structure (D-Phe-Cys-Tyr-D-Trp-Lys-Cys-THr-NH2 ) and very different characteristics from the known growth hormone (GH) active somatostatin analogs. This somatostatin structural derivative has no GH release inhibitory or antisecretory activity and does not bind to rat pituitary or the cortex, where all the known somatostatin receptor subtypes are expressed. TT-232 had previously been shown to inhibit the proliferation of a large number of cancer cell lines in vitro and reduce the size of different tumors in animal models in vivo. Materials and Methods: The therapeutic efficacy of TT-232 was evaluated in different long-term administration routes: the traditional injection (i.p. or s.c.) versus infusion treatment via s.c- or i.v.-inserted Alzet osmotic minipump, and on different types of transplantable rodent (S-180 sarcoma, P-388sc lymphoid leukemia, Colon-26 adenocarcinoma, MXT breast carcinoma, B-16 melanoma) and human tumor models (HT-18 lymphoid melanoma, T-47/D breast carcinoma, A-431 epidermoid carcinoma). On the basis of our previous experiments the optimum injected dose of TT-232 was found to be 15 μg/kg twice a day. This dose is equivalent to 0.6 μg/day by infusion therapy. Results: In our experiments, the best results were achieved when TT-232 was applied as an infused treatment. In the S-180 sarcoma and P-388sc lymphoid leukemia rodent tumor models the infusion treatment with TT-232 resulted in 61%-100% tumor growth inhibition and in 20%-60% of the mice being long-term and tumor-free survivors. In the aggressive Colon-26 adenocarcinoma and MXT breast carcinoma models, the infusion treatment resulted in 52%-75% tumor growth inhibition. In the B-16 melanoma model, the infusion treatments resulted in 47%-63% growth inhibition. The tumor growth inhibitory effect of infusion treatment with TT-232 on HT-18 human lymphoid melanoma tumor proved to be significant, resulting in 69%-79% decreases in tumor volume. In the T-47/D human breast carcinoma, the infusion treatment resulted in 48%-53% tumor growth inhibition. The tumor growth inhibitory effect of infusion treatment on A-431 human epidermoid carcinoma tumor resulted in 70%-74% decreases in tumor volume. Conclusion: The antitumor efficacy of TT-232 was seen in almost all the tumors investigated. In our study, the route of infusion was shown to increase drug efficacy relative to conventional delivery methods (injection). The results obtained from this study suggest that IT-232 is a promising new antitumor agent in cancer chemotherapy and a good candidate for delivery by continuous (infusion) therapy.

Original languageEnglish
Pages (from-to)2769-2774
Number of pages6
JournalAnticancer Research
Volume28
Issue number5 A
Publication statusPublished - Sep 2008

Fingerprint

Somatostatin
Neoplasms
Therapeutics
Melanoma
Growth
Breast Neoplasms
Sarcoma 180
Lymphoid Leukemia
TT2-32
Tumor Burden
Growth Hormone
Squamous Cell Carcinoma
Rodentia
Colon
Adenocarcinoma
Somatostatin Receptors
Injections
Antineoplastic Agents
Animal Models

Keywords

  • Implanted pump
  • Rodent and human tumor models
  • Somatostatin analog
  • TT-232

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

@article{5f79350e99b54ed5bd45533119b564c2,
title = "Continuous administration of the somatostatin structural derivative /TT-232/ by subcutaneously implanted osmotic pump improves the efficacy and potency of antitumor therapy in different mouse and human tumor models",
abstract = "Background: The somatostatin structural derivative, TT-232, has a special 5-residue ring structure (D-Phe-Cys-Tyr-D-Trp-Lys-Cys-THr-NH2 ) and very different characteristics from the known growth hormone (GH) active somatostatin analogs. This somatostatin structural derivative has no GH release inhibitory or antisecretory activity and does not bind to rat pituitary or the cortex, where all the known somatostatin receptor subtypes are expressed. TT-232 had previously been shown to inhibit the proliferation of a large number of cancer cell lines in vitro and reduce the size of different tumors in animal models in vivo. Materials and Methods: The therapeutic efficacy of TT-232 was evaluated in different long-term administration routes: the traditional injection (i.p. or s.c.) versus infusion treatment via s.c- or i.v.-inserted Alzet osmotic minipump, and on different types of transplantable rodent (S-180 sarcoma, P-388sc lymphoid leukemia, Colon-26 adenocarcinoma, MXT breast carcinoma, B-16 melanoma) and human tumor models (HT-18 lymphoid melanoma, T-47/D breast carcinoma, A-431 epidermoid carcinoma). On the basis of our previous experiments the optimum injected dose of TT-232 was found to be 15 μg/kg twice a day. This dose is equivalent to 0.6 μg/day by infusion therapy. Results: In our experiments, the best results were achieved when TT-232 was applied as an infused treatment. In the S-180 sarcoma and P-388sc lymphoid leukemia rodent tumor models the infusion treatment with TT-232 resulted in 61{\%}-100{\%} tumor growth inhibition and in 20{\%}-60{\%} of the mice being long-term and tumor-free survivors. In the aggressive Colon-26 adenocarcinoma and MXT breast carcinoma models, the infusion treatment resulted in 52{\%}-75{\%} tumor growth inhibition. In the B-16 melanoma model, the infusion treatments resulted in 47{\%}-63{\%} growth inhibition. The tumor growth inhibitory effect of infusion treatment with TT-232 on HT-18 human lymphoid melanoma tumor proved to be significant, resulting in 69{\%}-79{\%} decreases in tumor volume. In the T-47/D human breast carcinoma, the infusion treatment resulted in 48{\%}-53{\%} tumor growth inhibition. The tumor growth inhibitory effect of infusion treatment on A-431 human epidermoid carcinoma tumor resulted in 70{\%}-74{\%} decreases in tumor volume. Conclusion: The antitumor efficacy of TT-232 was seen in almost all the tumors investigated. In our study, the route of infusion was shown to increase drug efficacy relative to conventional delivery methods (injection). The results obtained from this study suggest that IT-232 is a promising new antitumor agent in cancer chemotherapy and a good candidate for delivery by continuous (infusion) therapy.",
keywords = "Implanted pump, Rodent and human tumor models, Somatostatin analog, TT-232",
author = "Miguel Tejeda and D. Ga{\'a}l and L. Hull{\'a}n and O. Csuka and R. Schwab and O. Szokoloczi and G. K{\'e}ri",
year = "2008",
month = "9",
language = "English",
volume = "28",
pages = "2769--2774",
journal = "Anticancer Research",
issn = "0250-7005",
publisher = "International Institute of Anticancer Research",
number = "5 A",

}

TY - JOUR

T1 - Continuous administration of the somatostatin structural derivative /TT-232/ by subcutaneously implanted osmotic pump improves the efficacy and potency of antitumor therapy in different mouse and human tumor models

AU - Tejeda, Miguel

AU - Gaál, D.

AU - Hullán, L.

AU - Csuka, O.

AU - Schwab, R.

AU - Szokoloczi, O.

AU - Kéri, G.

PY - 2008/9

Y1 - 2008/9

N2 - Background: The somatostatin structural derivative, TT-232, has a special 5-residue ring structure (D-Phe-Cys-Tyr-D-Trp-Lys-Cys-THr-NH2 ) and very different characteristics from the known growth hormone (GH) active somatostatin analogs. This somatostatin structural derivative has no GH release inhibitory or antisecretory activity and does not bind to rat pituitary or the cortex, where all the known somatostatin receptor subtypes are expressed. TT-232 had previously been shown to inhibit the proliferation of a large number of cancer cell lines in vitro and reduce the size of different tumors in animal models in vivo. Materials and Methods: The therapeutic efficacy of TT-232 was evaluated in different long-term administration routes: the traditional injection (i.p. or s.c.) versus infusion treatment via s.c- or i.v.-inserted Alzet osmotic minipump, and on different types of transplantable rodent (S-180 sarcoma, P-388sc lymphoid leukemia, Colon-26 adenocarcinoma, MXT breast carcinoma, B-16 melanoma) and human tumor models (HT-18 lymphoid melanoma, T-47/D breast carcinoma, A-431 epidermoid carcinoma). On the basis of our previous experiments the optimum injected dose of TT-232 was found to be 15 μg/kg twice a day. This dose is equivalent to 0.6 μg/day by infusion therapy. Results: In our experiments, the best results were achieved when TT-232 was applied as an infused treatment. In the S-180 sarcoma and P-388sc lymphoid leukemia rodent tumor models the infusion treatment with TT-232 resulted in 61%-100% tumor growth inhibition and in 20%-60% of the mice being long-term and tumor-free survivors. In the aggressive Colon-26 adenocarcinoma and MXT breast carcinoma models, the infusion treatment resulted in 52%-75% tumor growth inhibition. In the B-16 melanoma model, the infusion treatments resulted in 47%-63% growth inhibition. The tumor growth inhibitory effect of infusion treatment with TT-232 on HT-18 human lymphoid melanoma tumor proved to be significant, resulting in 69%-79% decreases in tumor volume. In the T-47/D human breast carcinoma, the infusion treatment resulted in 48%-53% tumor growth inhibition. The tumor growth inhibitory effect of infusion treatment on A-431 human epidermoid carcinoma tumor resulted in 70%-74% decreases in tumor volume. Conclusion: The antitumor efficacy of TT-232 was seen in almost all the tumors investigated. In our study, the route of infusion was shown to increase drug efficacy relative to conventional delivery methods (injection). The results obtained from this study suggest that IT-232 is a promising new antitumor agent in cancer chemotherapy and a good candidate for delivery by continuous (infusion) therapy.

AB - Background: The somatostatin structural derivative, TT-232, has a special 5-residue ring structure (D-Phe-Cys-Tyr-D-Trp-Lys-Cys-THr-NH2 ) and very different characteristics from the known growth hormone (GH) active somatostatin analogs. This somatostatin structural derivative has no GH release inhibitory or antisecretory activity and does not bind to rat pituitary or the cortex, where all the known somatostatin receptor subtypes are expressed. TT-232 had previously been shown to inhibit the proliferation of a large number of cancer cell lines in vitro and reduce the size of different tumors in animal models in vivo. Materials and Methods: The therapeutic efficacy of TT-232 was evaluated in different long-term administration routes: the traditional injection (i.p. or s.c.) versus infusion treatment via s.c- or i.v.-inserted Alzet osmotic minipump, and on different types of transplantable rodent (S-180 sarcoma, P-388sc lymphoid leukemia, Colon-26 adenocarcinoma, MXT breast carcinoma, B-16 melanoma) and human tumor models (HT-18 lymphoid melanoma, T-47/D breast carcinoma, A-431 epidermoid carcinoma). On the basis of our previous experiments the optimum injected dose of TT-232 was found to be 15 μg/kg twice a day. This dose is equivalent to 0.6 μg/day by infusion therapy. Results: In our experiments, the best results were achieved when TT-232 was applied as an infused treatment. In the S-180 sarcoma and P-388sc lymphoid leukemia rodent tumor models the infusion treatment with TT-232 resulted in 61%-100% tumor growth inhibition and in 20%-60% of the mice being long-term and tumor-free survivors. In the aggressive Colon-26 adenocarcinoma and MXT breast carcinoma models, the infusion treatment resulted in 52%-75% tumor growth inhibition. In the B-16 melanoma model, the infusion treatments resulted in 47%-63% growth inhibition. The tumor growth inhibitory effect of infusion treatment with TT-232 on HT-18 human lymphoid melanoma tumor proved to be significant, resulting in 69%-79% decreases in tumor volume. In the T-47/D human breast carcinoma, the infusion treatment resulted in 48%-53% tumor growth inhibition. The tumor growth inhibitory effect of infusion treatment on A-431 human epidermoid carcinoma tumor resulted in 70%-74% decreases in tumor volume. Conclusion: The antitumor efficacy of TT-232 was seen in almost all the tumors investigated. In our study, the route of infusion was shown to increase drug efficacy relative to conventional delivery methods (injection). The results obtained from this study suggest that IT-232 is a promising new antitumor agent in cancer chemotherapy and a good candidate for delivery by continuous (infusion) therapy.

KW - Implanted pump

KW - Rodent and human tumor models

KW - Somatostatin analog

KW - TT-232

UR - http://www.scopus.com/inward/record.url?scp=55749109383&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=55749109383&partnerID=8YFLogxK

M3 - Article

C2 - 19035308

AN - SCOPUS:55749109383

VL - 28

SP - 2769

EP - 2774

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

IS - 5 A

ER -