Antitumor effect of interleukin 7 in combination with local hyperthermia in mice bearing B16a melanoma cells

Bo Wu, Rong‐Nian ‐N Shen, Wen‐Xue ‐X Wang, Hal E. Broxmeyer, Li Lu

Research output: Contribution to journalArticle

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Abstract

Interleukin (IL)‐7 has been evaluated for its influence, alone or in combination with local hyperthermia (LH), on B16a melanoma‐bearing mice. Six‐ to eight‐week‐old C57BL/6J male mice were inoculated s.c. with 5 × 105 tumor cells into the left hind limb. Mice were randomly divided into four groups, and treated s.c. with IL‐7 (5 ng) or saline as control, twice a day for three weeks beginning eight days after tumor inoculation. LH, using hot water circulator at 43 ± 0.2d̀C for 30 min, was induced to the limb with tumor twice a week for two weeks. Size of the primary tumor was measured every other day for five weeks. Mice were sacrificed five weeks after tumor inoculation. The size of the primary tumor and the number of lung metastases were reduced in mice treated either with IL‐7 or LH alone. As a control for IL‐7, gran‐ulocyte colony stimulating factor (G‐CSF) alone had no effect on primary tumor size or number of lung metastases. The greatest antitumor effect was observed in mice treated with IL‐7 in combination with LH. Survival was prolonged significantly only in mice treated with IL‐7 plus LH compared with that of mice treated with saline. Decreased natural killer (NK) cell activity, number of Thy1.2 cells, and ratio of L3T4+/Lyt2+ cells were associated with tumor growth. These parameters were restored in mice treated with IL‐7 plus LH. Increases in levels of IL‐1α, IL‐6, tumor necrosis factor (TNFα) and interferon (IFNγ) were associated with an increase in the survival of tumor‐bearing mice treated with IL‐7 and/or LH. These results suggest that changes in T‐cell, NK cell and cytokines such as IL‐1α, IL‐6, TNF‐α and IFN‐γ in response to IL‐7 and/or LH might account for prolonged survival of B16a melanoma‐bearing mice and that IL‐7 might be useful as a potential antitumor agent combined with other therapy in certain malignant solid tumors with metastases.

Original languageEnglish (US)
Pages (from-to)412-421
Number of pages10
JournalSTEM CELLS
Volume11
Issue number5
DOIs
StatePublished - 1993

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Neoplasm Transplantation
Antitumor Drug Screening Assays
Interleukin-7
Combined Modality Therapy
Experimental Melanomas
Induced Hyperthermia
T-Lymphocyte Subsets
Inbred C57BL Mouse
Natural Killer Cells
Antineoplastic Agents
Melanoma
Lung Neoplasms
Fever
Spleen
Cytokines
Neoplasms
Interleukin-1alpha
Neoplasm Metastasis
Interleukin-6
Extremities

Keywords

  • B16a melanoma
  • Cytokines
  • Hyperthermia
  • IL‐7
  • Natural killer cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Antitumor effect of interleukin 7 in combination with local hyperthermia in mice bearing B16a melanoma cells. / Wu, Bo; Shen, Rong‐Nian ‐N; Wang, Wen‐Xue ‐X; Broxmeyer, Hal E.; Lu, Li.

In: STEM CELLS, Vol. 11, No. 5, 1993, p. 412-421.

Research output: Contribution to journalArticle

Wu, Bo ; Shen, Rong‐Nian ‐N ; Wang, Wen‐Xue ‐X ; Broxmeyer, Hal E. ; Lu, Li. / Antitumor effect of interleukin 7 in combination with local hyperthermia in mice bearing B16a melanoma cells. In: STEM CELLS. 1993 ; Vol. 11, No. 5. pp. 412-421.
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AB - Interleukin (IL)‐7 has been evaluated for its influence, alone or in combination with local hyperthermia (LH), on B16a melanoma‐bearing mice. Six‐ to eight‐week‐old C57BL/6J male mice were inoculated s.c. with 5 × 105 tumor cells into the left hind limb. Mice were randomly divided into four groups, and treated s.c. with IL‐7 (5 ng) or saline as control, twice a day for three weeks beginning eight days after tumor inoculation. LH, using hot water circulator at 43 ± 0.2d̀C for 30 min, was induced to the limb with tumor twice a week for two weeks. Size of the primary tumor was measured every other day for five weeks. Mice were sacrificed five weeks after tumor inoculation. The size of the primary tumor and the number of lung metastases were reduced in mice treated either with IL‐7 or LH alone. As a control for IL‐7, gran‐ulocyte colony stimulating factor (G‐CSF) alone had no effect on primary tumor size or number of lung metastases. The greatest antitumor effect was observed in mice treated with IL‐7 in combination with LH. Survival was prolonged significantly only in mice treated with IL‐7 plus LH compared with that of mice treated with saline. Decreased natural killer (NK) cell activity, number of Thy1.2 cells, and ratio of L3T4+/Lyt2+ cells were associated with tumor growth. These parameters were restored in mice treated with IL‐7 plus LH. Increases in levels of IL‐1α, IL‐6, tumor necrosis factor (TNFα) and interferon (IFNγ) were associated with an increase in the survival of tumor‐bearing mice treated with IL‐7 and/or LH. These results suggest that changes in T‐cell, NK cell and cytokines such as IL‐1α, IL‐6, TNF‐α and IFN‐γ in response to IL‐7 and/or LH might account for prolonged survival of B16a melanoma‐bearing mice and that IL‐7 might be useful as a potential antitumor agent combined with other therapy in certain malignant solid tumors with metastases.

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