Peptide analogues alter the progression of premalignant lesions, as measured by Photofrin fluorescence

Charles Liebow, David H. Crean, Andrew V Schally, Thomas S. Mang

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Somatostatin analogue RC-160 and bombesin/gastrin-releasing peptide antagonist RC-3095 were infused at 2 μg per day via miniosmotic pumps implanted s.c. in hamsters with premalignant disease to examine the effect of these peptides on cancer promotion and progression. These analogues have been shown to inhibit growth of certain tumors, especially those that overexpress tyrosine kinase activity. Progression of premalignant lesions initiated by applying 0.5% 9,10-dimethyl-1,2-benzanthracene (DMBA) to the hamster buccal cheek pouch was measured by Photofrin-induced fluorescence 24 hr after injecting the porphyrin (1.0 mg/kg) by using in vivo fluorescence photometry. This method of monitoring progression was reaffirmed by the observations that fluorescence increased significantly as compared with controls in lesions receiving 4 additional weeks of continuous promotion by DMBA application (P < 0.01 in two independent trials) and in lesions receiving transient promotion by laser incision (P < 0.01 and < 0.05 at the same time in the two trials). Twelve weeks after treatment, fluorescence had decreased significantly among animals treated for 2 weeks with RC-3095 (control, 0.53 ± 0.03 V vs. RC-3095, 0.28 ± 0.03 V; P < 0.0005) or with RC-160 (control, 0.85 ± 0.03 V vs. RC-160, 0.24 ± 0.03 V; P < 0.0001). These data were obtained 20 weeks after DMBA initiation. Thus, treatment with RC-160 and RC-3095 decreased the progression, measured by fluorescence, compared with control animals. In addition, there was also an absolute continuous decrease in fluorescence for the 22 weeks after the cessation of RC-160 treatment. That the changes in tumor progression produced by RC-160 extended beyond the treatment period supports the hypothesis that the changes were irreversible. Histopathological analysis revealed normal tissue and/or mild-moderate dysplasia in hamster buccal mucosa treated with the RC-160 (an improvement compared to pretreatment), whereas 40% of the animals receiving no treatment after DMBA initiation developed invasive squamous cell carcinomas after 20 weeks. These results show that the antagonists of bombesin/gastrin-releasing peptide can delay the development of malignancies and the agonists of somatostatin can potentially reverse this development.

Original languageEnglish
Pages (from-to)1897-1901
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number5
StatePublished - Mar 1 1993
Externally publishedYes

Fingerprint

Dihematoporphyrin Ether
Fluorescence
9,10-Dimethyl-1,2-benzanthracene
Peptides
Cricetinae
Gastrin-Releasing Peptide
Bombesin
Cheek
Somatostatin
Neoplasms
Photometry
Porphyrins
Mouth Mucosa
vapreotide
Protein-Tyrosine Kinases
Squamous Cell Carcinoma
Lasers
Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-bombesin (6-14)
Growth

Keywords

  • Bombesin antagonist RC-3095
  • Dimethylbenzanthracene
  • Fluorescence photometry
  • Hamster buccal cheek pouch
  • Somatostatin analogue RC-160

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Peptide analogues alter the progression of premalignant lesions, as measured by Photofrin fluorescence. / Liebow, Charles; Crean, David H.; Schally, Andrew V; Mang, Thomas S.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 90, No. 5, 01.03.1993, p. 1897-1901.

Research output: Contribution to journalArticle

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abstract = "Somatostatin analogue RC-160 and bombesin/gastrin-releasing peptide antagonist RC-3095 were infused at 2 μg per day via miniosmotic pumps implanted s.c. in hamsters with premalignant disease to examine the effect of these peptides on cancer promotion and progression. These analogues have been shown to inhibit growth of certain tumors, especially those that overexpress tyrosine kinase activity. Progression of premalignant lesions initiated by applying 0.5{\%} 9,10-dimethyl-1,2-benzanthracene (DMBA) to the hamster buccal cheek pouch was measured by Photofrin-induced fluorescence 24 hr after injecting the porphyrin (1.0 mg/kg) by using in vivo fluorescence photometry. This method of monitoring progression was reaffirmed by the observations that fluorescence increased significantly as compared with controls in lesions receiving 4 additional weeks of continuous promotion by DMBA application (P < 0.01 in two independent trials) and in lesions receiving transient promotion by laser incision (P < 0.01 and < 0.05 at the same time in the two trials). Twelve weeks after treatment, fluorescence had decreased significantly among animals treated for 2 weeks with RC-3095 (control, 0.53 ± 0.03 V vs. RC-3095, 0.28 ± 0.03 V; P < 0.0005) or with RC-160 (control, 0.85 ± 0.03 V vs. RC-160, 0.24 ± 0.03 V; P < 0.0001). These data were obtained 20 weeks after DMBA initiation. Thus, treatment with RC-160 and RC-3095 decreased the progression, measured by fluorescence, compared with control animals. In addition, there was also an absolute continuous decrease in fluorescence for the 22 weeks after the cessation of RC-160 treatment. That the changes in tumor progression produced by RC-160 extended beyond the treatment period supports the hypothesis that the changes were irreversible. Histopathological analysis revealed normal tissue and/or mild-moderate dysplasia in hamster buccal mucosa treated with the RC-160 (an improvement compared to pretreatment), whereas 40{\%} of the animals receiving no treatment after DMBA initiation developed invasive squamous cell carcinomas after 20 weeks. These results show that the antagonists of bombesin/gastrin-releasing peptide can delay the development of malignancies and the agonists of somatostatin can potentially reverse this development.",
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N2 - Somatostatin analogue RC-160 and bombesin/gastrin-releasing peptide antagonist RC-3095 were infused at 2 μg per day via miniosmotic pumps implanted s.c. in hamsters with premalignant disease to examine the effect of these peptides on cancer promotion and progression. These analogues have been shown to inhibit growth of certain tumors, especially those that overexpress tyrosine kinase activity. Progression of premalignant lesions initiated by applying 0.5% 9,10-dimethyl-1,2-benzanthracene (DMBA) to the hamster buccal cheek pouch was measured by Photofrin-induced fluorescence 24 hr after injecting the porphyrin (1.0 mg/kg) by using in vivo fluorescence photometry. This method of monitoring progression was reaffirmed by the observations that fluorescence increased significantly as compared with controls in lesions receiving 4 additional weeks of continuous promotion by DMBA application (P < 0.01 in two independent trials) and in lesions receiving transient promotion by laser incision (P < 0.01 and < 0.05 at the same time in the two trials). Twelve weeks after treatment, fluorescence had decreased significantly among animals treated for 2 weeks with RC-3095 (control, 0.53 ± 0.03 V vs. RC-3095, 0.28 ± 0.03 V; P < 0.0005) or with RC-160 (control, 0.85 ± 0.03 V vs. RC-160, 0.24 ± 0.03 V; P < 0.0001). These data were obtained 20 weeks after DMBA initiation. Thus, treatment with RC-160 and RC-3095 decreased the progression, measured by fluorescence, compared with control animals. In addition, there was also an absolute continuous decrease in fluorescence for the 22 weeks after the cessation of RC-160 treatment. That the changes in tumor progression produced by RC-160 extended beyond the treatment period supports the hypothesis that the changes were irreversible. Histopathological analysis revealed normal tissue and/or mild-moderate dysplasia in hamster buccal mucosa treated with the RC-160 (an improvement compared to pretreatment), whereas 40% of the animals receiving no treatment after DMBA initiation developed invasive squamous cell carcinomas after 20 weeks. These results show that the antagonists of bombesin/gastrin-releasing peptide can delay the development of malignancies and the agonists of somatostatin can potentially reverse this development.

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