Systemic interleukin 2 therapy for human prostate tumors in a nude mouse model

Jeffrey A. Triest, David Grignon, Michael L. Cher, Sosa V. Kocheril, Emily J. Montecillo, Bharat Talati, Samuel Tekyi-Mensah, J. Edson Pontes, Gilda G. Hillman

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Once the regional lymph nodes become involved in prostate carcinoma, 85% of patients develop distant metastases within 5 years, and metastatic disease is difficult to treat. We have investigated the effect of systemic interleukin 2 (IL-2) treatment on metastatic prostate carcinoma using a xenograft tumor model. Cells from a PC-3/IF cell line, produced by intrafemoral injection of human PC-3 prostate carcinoma cells, were injected in the prostate of Balb/c nude mice. Prostate tumors and para-aortic lymph nodes were resected, and tumor cells were recultured and passaged in the prostate in vivo to produce new cell lines. On day 6 following prostatic injection of these cell lines, mice were treated with i.p. injections of IL- 2 at 25,000-50,000 units/day for 5 consecutive days. The effect of IL-2 on tumor progression was assessed, and histological studies were performed on prostate tumor and lymph node sections. The tumor cell lines generated by serial prostate injection were tumorigenic and metastasized to regional para- aortic lymph nodes. Tumors of 0.4 cm were obtained by day 16 and grew to 1- 1.5 cm by day 40 with metastasis to para-aortic lymph nodes. Following two to three weekly courses of 5 days of 25,000-40,000 units/day of IL-2, the growth of prostate tumors was inhibited by 94%. Higher doses of 50,000 units/day were toxic. Histologically, prostate sections showed vascular damage manifested by multifocal hemorrhages and an influx of lymphocytes and polymorphonuclear cells into disintegrating tumors and areas of necrosis containing numerous apoptotic cells. In contrast to control mice, para- aortic lymph nodes were not enlarged in responding mice. These findings suggest that systemic IL-2 therapy can induce an antitumor response in prostate tumors and control their growth and metastasis.

Original languageEnglish (US)
Pages (from-to)2009-2014
Number of pages6
JournalClinical Cancer Research
Volume4
Issue number8
StatePublished - Aug 1998
Externally publishedYes

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Nude Mice
Interleukin-2
Prostate
Neoplasms
Lymph Nodes
Therapeutics
Injections
Neoplasm Metastasis
Carcinoma
Cell Line
Poisons
Growth
Tumor Cell Line
Heterografts
Blood Vessels
Necrosis
Lymphocytes
Hemorrhage

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Triest, J. A., Grignon, D., Cher, M. L., Kocheril, S. V., Montecillo, E. J., Talati, B., ... Hillman, G. G. (1998). Systemic interleukin 2 therapy for human prostate tumors in a nude mouse model. Clinical Cancer Research, 4(8), 2009-2014.

Systemic interleukin 2 therapy for human prostate tumors in a nude mouse model. / Triest, Jeffrey A.; Grignon, David; Cher, Michael L.; Kocheril, Sosa V.; Montecillo, Emily J.; Talati, Bharat; Tekyi-Mensah, Samuel; Pontes, J. Edson; Hillman, Gilda G.

In: Clinical Cancer Research, Vol. 4, No. 8, 08.1998, p. 2009-2014.

Research output: Contribution to journalArticle

Triest, JA, Grignon, D, Cher, ML, Kocheril, SV, Montecillo, EJ, Talati, B, Tekyi-Mensah, S, Pontes, JE & Hillman, GG 1998, 'Systemic interleukin 2 therapy for human prostate tumors in a nude mouse model', Clinical Cancer Research, vol. 4, no. 8, pp. 2009-2014.
Triest JA, Grignon D, Cher ML, Kocheril SV, Montecillo EJ, Talati B et al. Systemic interleukin 2 therapy for human prostate tumors in a nude mouse model. Clinical Cancer Research. 1998 Aug;4(8):2009-2014.
Triest, Jeffrey A. ; Grignon, David ; Cher, Michael L. ; Kocheril, Sosa V. ; Montecillo, Emily J. ; Talati, Bharat ; Tekyi-Mensah, Samuel ; Pontes, J. Edson ; Hillman, Gilda G. / Systemic interleukin 2 therapy for human prostate tumors in a nude mouse model. In: Clinical Cancer Research. 1998 ; Vol. 4, No. 8. pp. 2009-2014.
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abstract = "Once the regional lymph nodes become involved in prostate carcinoma, 85{\%} of patients develop distant metastases within 5 years, and metastatic disease is difficult to treat. We have investigated the effect of systemic interleukin 2 (IL-2) treatment on metastatic prostate carcinoma using a xenograft tumor model. Cells from a PC-3/IF cell line, produced by intrafemoral injection of human PC-3 prostate carcinoma cells, were injected in the prostate of Balb/c nude mice. Prostate tumors and para-aortic lymph nodes were resected, and tumor cells were recultured and passaged in the prostate in vivo to produce new cell lines. On day 6 following prostatic injection of these cell lines, mice were treated with i.p. injections of IL- 2 at 25,000-50,000 units/day for 5 consecutive days. The effect of IL-2 on tumor progression was assessed, and histological studies were performed on prostate tumor and lymph node sections. The tumor cell lines generated by serial prostate injection were tumorigenic and metastasized to regional para- aortic lymph nodes. Tumors of 0.4 cm were obtained by day 16 and grew to 1- 1.5 cm by day 40 with metastasis to para-aortic lymph nodes. Following two to three weekly courses of 5 days of 25,000-40,000 units/day of IL-2, the growth of prostate tumors was inhibited by 94{\%}. Higher doses of 50,000 units/day were toxic. Histologically, prostate sections showed vascular damage manifested by multifocal hemorrhages and an influx of lymphocytes and polymorphonuclear cells into disintegrating tumors and areas of necrosis containing numerous apoptotic cells. In contrast to control mice, para- aortic lymph nodes were not enlarged in responding mice. These findings suggest that systemic IL-2 therapy can induce an antitumor response in prostate tumors and control their growth and metastasis.",
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N2 - Once the regional lymph nodes become involved in prostate carcinoma, 85% of patients develop distant metastases within 5 years, and metastatic disease is difficult to treat. We have investigated the effect of systemic interleukin 2 (IL-2) treatment on metastatic prostate carcinoma using a xenograft tumor model. Cells from a PC-3/IF cell line, produced by intrafemoral injection of human PC-3 prostate carcinoma cells, were injected in the prostate of Balb/c nude mice. Prostate tumors and para-aortic lymph nodes were resected, and tumor cells were recultured and passaged in the prostate in vivo to produce new cell lines. On day 6 following prostatic injection of these cell lines, mice were treated with i.p. injections of IL- 2 at 25,000-50,000 units/day for 5 consecutive days. The effect of IL-2 on tumor progression was assessed, and histological studies were performed on prostate tumor and lymph node sections. The tumor cell lines generated by serial prostate injection were tumorigenic and metastasized to regional para- aortic lymph nodes. Tumors of 0.4 cm were obtained by day 16 and grew to 1- 1.5 cm by day 40 with metastasis to para-aortic lymph nodes. Following two to three weekly courses of 5 days of 25,000-40,000 units/day of IL-2, the growth of prostate tumors was inhibited by 94%. Higher doses of 50,000 units/day were toxic. Histologically, prostate sections showed vascular damage manifested by multifocal hemorrhages and an influx of lymphocytes and polymorphonuclear cells into disintegrating tumors and areas of necrosis containing numerous apoptotic cells. In contrast to control mice, para- aortic lymph nodes were not enlarged in responding mice. These findings suggest that systemic IL-2 therapy can induce an antitumor response in prostate tumors and control their growth and metastasis.

AB - Once the regional lymph nodes become involved in prostate carcinoma, 85% of patients develop distant metastases within 5 years, and metastatic disease is difficult to treat. We have investigated the effect of systemic interleukin 2 (IL-2) treatment on metastatic prostate carcinoma using a xenograft tumor model. Cells from a PC-3/IF cell line, produced by intrafemoral injection of human PC-3 prostate carcinoma cells, were injected in the prostate of Balb/c nude mice. Prostate tumors and para-aortic lymph nodes were resected, and tumor cells were recultured and passaged in the prostate in vivo to produce new cell lines. On day 6 following prostatic injection of these cell lines, mice were treated with i.p. injections of IL- 2 at 25,000-50,000 units/day for 5 consecutive days. The effect of IL-2 on tumor progression was assessed, and histological studies were performed on prostate tumor and lymph node sections. The tumor cell lines generated by serial prostate injection were tumorigenic and metastasized to regional para- aortic lymph nodes. Tumors of 0.4 cm were obtained by day 16 and grew to 1- 1.5 cm by day 40 with metastasis to para-aortic lymph nodes. Following two to three weekly courses of 5 days of 25,000-40,000 units/day of IL-2, the growth of prostate tumors was inhibited by 94%. Higher doses of 50,000 units/day were toxic. Histologically, prostate sections showed vascular damage manifested by multifocal hemorrhages and an influx of lymphocytes and polymorphonuclear cells into disintegrating tumors and areas of necrosis containing numerous apoptotic cells. In contrast to control mice, para- aortic lymph nodes were not enlarged in responding mice. These findings suggest that systemic IL-2 therapy can induce an antitumor response in prostate tumors and control their growth and metastasis.

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