Inhibition of human gastric adenocarcinoma xenograft growth in nude mice by α-difluoromethylornithine

J. R. Upp, R. D. Beauchamp, Courtney Townsend, S. C. Barranco, Pomila Singh, S. Rajaraman, E. James, J. C. Thompson

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

We studied the effect of inhibition of polyamine biosynthesis by α-difluoromethylornithine on the growth of a human gastric adenocarcinoma (CLEES) xenotransplanted in nude mice. CLEES is a well-differentiated gastric adenocarcinoma of the intestinal type. The doubling time has ranged from 7 to 10 days through 11 passages. Electron microscopic and immunohistochemical studies comparing the original tumor and xenotransplants showed similar structure and similar amounts of carcinoembryonic antigen. Polyamine biosynthesis is required for cell division. α-Difluoromethylornithine inhibits ornithine decarboxylase, the rate-limiting enzyme in polyamine biosynthesis. In this study, 48 athymic mice were used in two experiments. In the first experiment, two groups of 12 mice each were inoculated with CLEES tumor cells and received either tap water or a 3% α-difluoromethylornithine solution as drinking water. Tumor size was measured twice weekly. Tumor size was significantly decreased from controls by the fourth week of treatment and at all points of analysis thereafter for 7 wk. In the second experiment, α-difluoromethylornithine significantly reduced tumor concentrations of the polyamines putrescine and spermidine. In addition, the tumor content of DNA was significantly reduced in treated mice (0.64 ± 0.16 mg) compared to controls (4.76 ± 0.92 mg). Our data suggest that inhibition of polyamine biosynthesis may be a useful component of multidrug chemotherapy for human gastric adenocarcinoma. Establishment of tumor lines such as this gastric adenocarcinoma will facilitate further studies on the biological behavior of human gastric cancer and its response to chemotherapeutic manipulation in vivo.

Original languageEnglish (US)
Pages (from-to)3265-3269
Number of pages5
JournalCancer Research
Volume48
Issue number11
StatePublished - 1988

Fingerprint

Eflornithine
Heterografts
Nude Mice
Stomach
Adenocarcinoma
Polyamines
Growth
Neoplasms
Ornithine Decarboxylase
Putrescine
Spermidine
Carcinoembryonic Antigen
Drinking Water
Cell Division
Stomach Neoplasms
Electrons
Drug Therapy
Water
DNA
Enzymes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Upp, J. R., Beauchamp, R. D., Townsend, C., Barranco, S. C., Singh, P., Rajaraman, S., ... Thompson, J. C. (1988). Inhibition of human gastric adenocarcinoma xenograft growth in nude mice by α-difluoromethylornithine. Cancer Research, 48(11), 3265-3269.

Inhibition of human gastric adenocarcinoma xenograft growth in nude mice by α-difluoromethylornithine. / Upp, J. R.; Beauchamp, R. D.; Townsend, Courtney; Barranco, S. C.; Singh, Pomila; Rajaraman, S.; James, E.; Thompson, J. C.

In: Cancer Research, Vol. 48, No. 11, 1988, p. 3265-3269.

Research output: Contribution to journalArticle

Upp, JR, Beauchamp, RD, Townsend, C, Barranco, SC, Singh, P, Rajaraman, S, James, E & Thompson, JC 1988, 'Inhibition of human gastric adenocarcinoma xenograft growth in nude mice by α-difluoromethylornithine', Cancer Research, vol. 48, no. 11, pp. 3265-3269.
Upp, J. R. ; Beauchamp, R. D. ; Townsend, Courtney ; Barranco, S. C. ; Singh, Pomila ; Rajaraman, S. ; James, E. ; Thompson, J. C. / Inhibition of human gastric adenocarcinoma xenograft growth in nude mice by α-difluoromethylornithine. In: Cancer Research. 1988 ; Vol. 48, No. 11. pp. 3265-3269.
@article{7bc46df806bd4923a798c6d0789ffd94,
title = "Inhibition of human gastric adenocarcinoma xenograft growth in nude mice by α-difluoromethylornithine",
abstract = "We studied the effect of inhibition of polyamine biosynthesis by α-difluoromethylornithine on the growth of a human gastric adenocarcinoma (CLEES) xenotransplanted in nude mice. CLEES is a well-differentiated gastric adenocarcinoma of the intestinal type. The doubling time has ranged from 7 to 10 days through 11 passages. Electron microscopic and immunohistochemical studies comparing the original tumor and xenotransplants showed similar structure and similar amounts of carcinoembryonic antigen. Polyamine biosynthesis is required for cell division. α-Difluoromethylornithine inhibits ornithine decarboxylase, the rate-limiting enzyme in polyamine biosynthesis. In this study, 48 athymic mice were used in two experiments. In the first experiment, two groups of 12 mice each were inoculated with CLEES tumor cells and received either tap water or a 3{\%} α-difluoromethylornithine solution as drinking water. Tumor size was measured twice weekly. Tumor size was significantly decreased from controls by the fourth week of treatment and at all points of analysis thereafter for 7 wk. In the second experiment, α-difluoromethylornithine significantly reduced tumor concentrations of the polyamines putrescine and spermidine. In addition, the tumor content of DNA was significantly reduced in treated mice (0.64 ± 0.16 mg) compared to controls (4.76 ± 0.92 mg). Our data suggest that inhibition of polyamine biosynthesis may be a useful component of multidrug chemotherapy for human gastric adenocarcinoma. Establishment of tumor lines such as this gastric adenocarcinoma will facilitate further studies on the biological behavior of human gastric cancer and its response to chemotherapeutic manipulation in vivo.",
author = "Upp, {J. R.} and Beauchamp, {R. D.} and Courtney Townsend and Barranco, {S. C.} and Pomila Singh and S. Rajaraman and E. James and Thompson, {J. C.}",
year = "1988",
language = "English (US)",
volume = "48",
pages = "3265--3269",
journal = "Journal of Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "11",

}

TY - JOUR

T1 - Inhibition of human gastric adenocarcinoma xenograft growth in nude mice by α-difluoromethylornithine

AU - Upp, J. R.

AU - Beauchamp, R. D.

AU - Townsend, Courtney

AU - Barranco, S. C.

AU - Singh, Pomila

AU - Rajaraman, S.

AU - James, E.

AU - Thompson, J. C.

PY - 1988

Y1 - 1988

N2 - We studied the effect of inhibition of polyamine biosynthesis by α-difluoromethylornithine on the growth of a human gastric adenocarcinoma (CLEES) xenotransplanted in nude mice. CLEES is a well-differentiated gastric adenocarcinoma of the intestinal type. The doubling time has ranged from 7 to 10 days through 11 passages. Electron microscopic and immunohistochemical studies comparing the original tumor and xenotransplants showed similar structure and similar amounts of carcinoembryonic antigen. Polyamine biosynthesis is required for cell division. α-Difluoromethylornithine inhibits ornithine decarboxylase, the rate-limiting enzyme in polyamine biosynthesis. In this study, 48 athymic mice were used in two experiments. In the first experiment, two groups of 12 mice each were inoculated with CLEES tumor cells and received either tap water or a 3% α-difluoromethylornithine solution as drinking water. Tumor size was measured twice weekly. Tumor size was significantly decreased from controls by the fourth week of treatment and at all points of analysis thereafter for 7 wk. In the second experiment, α-difluoromethylornithine significantly reduced tumor concentrations of the polyamines putrescine and spermidine. In addition, the tumor content of DNA was significantly reduced in treated mice (0.64 ± 0.16 mg) compared to controls (4.76 ± 0.92 mg). Our data suggest that inhibition of polyamine biosynthesis may be a useful component of multidrug chemotherapy for human gastric adenocarcinoma. Establishment of tumor lines such as this gastric adenocarcinoma will facilitate further studies on the biological behavior of human gastric cancer and its response to chemotherapeutic manipulation in vivo.

AB - We studied the effect of inhibition of polyamine biosynthesis by α-difluoromethylornithine on the growth of a human gastric adenocarcinoma (CLEES) xenotransplanted in nude mice. CLEES is a well-differentiated gastric adenocarcinoma of the intestinal type. The doubling time has ranged from 7 to 10 days through 11 passages. Electron microscopic and immunohistochemical studies comparing the original tumor and xenotransplants showed similar structure and similar amounts of carcinoembryonic antigen. Polyamine biosynthesis is required for cell division. α-Difluoromethylornithine inhibits ornithine decarboxylase, the rate-limiting enzyme in polyamine biosynthesis. In this study, 48 athymic mice were used in two experiments. In the first experiment, two groups of 12 mice each were inoculated with CLEES tumor cells and received either tap water or a 3% α-difluoromethylornithine solution as drinking water. Tumor size was measured twice weekly. Tumor size was significantly decreased from controls by the fourth week of treatment and at all points of analysis thereafter for 7 wk. In the second experiment, α-difluoromethylornithine significantly reduced tumor concentrations of the polyamines putrescine and spermidine. In addition, the tumor content of DNA was significantly reduced in treated mice (0.64 ± 0.16 mg) compared to controls (4.76 ± 0.92 mg). Our data suggest that inhibition of polyamine biosynthesis may be a useful component of multidrug chemotherapy for human gastric adenocarcinoma. Establishment of tumor lines such as this gastric adenocarcinoma will facilitate further studies on the biological behavior of human gastric cancer and its response to chemotherapeutic manipulation in vivo.

UR - http://www.scopus.com/inward/record.url?scp=0023943457&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023943457&partnerID=8YFLogxK

M3 - Article

C2 - 3130188

AN - SCOPUS:0023943457

VL - 48

SP - 3265

EP - 3269

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0008-5472

IS - 11

ER -