Intra-peritoneal hyperthermia combining α-galactosylceramide in the treatment of ovarian cancer

The purpose of this study was to investigate the anti-tumor effect and potential mechanisms of i.p. hyperthermia in combination with α-galactosylceramide (α-GalCer) for the treatment of ovarian cancer. In this study, immuno-competent tumor models were established using murine ovarian cancer cell lin...

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Veröffentlicht in:PloS one 2013-07, Vol.8 (7), p.e69336-e69336
Hauptverfasser: Wu, Chao-Chih, Chuang, Yin-Ting, Hsu, Yun-Ting, Huang, Jung-Tang, Wu, T-C, Hung, Chien-Fu, Yang, Yuh-Cheng, Chang, Chih-Long
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container_issue 7
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container_title PloS one
container_volume 8
creator Wu, Chao-Chih
Chuang, Yin-Ting
Hsu, Yun-Ting
Huang, Jung-Tang
Wu, T-C
Hung, Chien-Fu
Yang, Yuh-Cheng
Chang, Chih-Long
description The purpose of this study was to investigate the anti-tumor effect and potential mechanisms of i.p. hyperthermia in combination with α-galactosylceramide (α-GalCer) for the treatment of ovarian cancer. In this study, immuno-competent tumor models were established using murine ovarian cancer cell lines and treated with i.p. hyperthermia combining α-GalCer. Th1/Th2 cytokine expression profiles in the serum, NK cell cytotoxicity and phagocytic activities of dendritic cells (DCs) were assayed. We also analyzed the number of CD8(+)/IFN-γ(+) tumor specific cytotoxic T cells, as well as the tumor growth based on depletion of lymphocyte sub-population. Therapeutic effect on those ovarian tumors was monitored by a non-invasive luminescent imaging system. Intra-peritoneal hyperthermia induced significant pro-inflammatory cytokines expression, and sustained the response of NK and DCs induced by α-GalCer treatment. The combination treatment enhanced the cytotoxic T lymphocyte (CTL) immune response in two mouse ovarian cancer models. This novel treatment modality by combination of hyperthermia and glycolipid provides a pronounced anti-tumor immune response and better survival. In conclusion, intra-peritoneal hyperthermia enhanced the pro-inflammatory cytokine secretion and phagocytic activity of DCs stimulated by α-GalCer. The subsequent CTL immune response induced by α-GalCer was further strengthened by combining with i.p. hyperthermia. Both innate and adaptive immunities were involved and resulted in a superior therapeutic effect in treating the ovarian cancer.
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In conclusion, intra-peritoneal hyperthermia enhanced the pro-inflammatory cytokine secretion and phagocytic activity of DCs stimulated by α-GalCer. The subsequent CTL immune response induced by α-GalCer was further strengthened by combining with i.p. hyperthermia. 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In this study, immuno-competent tumor models were established using murine ovarian cancer cell lines and treated with i.p. hyperthermia combining α-GalCer. Th1/Th2 cytokine expression profiles in the serum, NK cell cytotoxicity and phagocytic activities of dendritic cells (DCs) were assayed. We also analyzed the number of CD8(+)/IFN-γ(+) tumor specific cytotoxic T cells, as well as the tumor growth based on depletion of lymphocyte sub-population. Therapeutic effect on those ovarian tumors was monitored by a non-invasive luminescent imaging system. Intra-peritoneal hyperthermia induced significant pro-inflammatory cytokines expression, and sustained the response of NK and DCs induced by α-GalCer treatment. The combination treatment enhanced the cytotoxic T lymphocyte (CTL) immune response in two mouse ovarian cancer models. This novel treatment modality by combination of hyperthermia and glycolipid provides a pronounced anti-tumor immune response and better survival. In conclusion, intra-peritoneal hyperthermia enhanced the pro-inflammatory cytokine secretion and phagocytic activity of DCs stimulated by α-GalCer. The subsequent CTL immune response induced by α-GalCer was further strengthened by combining with i.p. hyperthermia. Both innate and adaptive immunities were involved and resulted in a superior therapeutic effect in treating the ovarian cancer.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23935988</pmid><doi>10.1371/journal.pone.0069336</doi><oa>free_for_read</oa></addata></record>
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subjects Animal models
Animals
Anticancer properties
Antigens
Biology
Cancer
CD8 antigen
CD8-Positive T-Lymphocytes - drug effects
CD8-Positive T-Lymphocytes - metabolism
Cell Death - drug effects
Cell Line, Tumor
Chemotherapy
Cytokines
Cytokines - blood
Cytokines - secretion
Cytotoxicity
Dendritic cells
Dendritic Cells - drug effects
Dendritic Cells - metabolism
Diabetes
Disease Models, Animal
Electrical engineering
Female
Fever
Galactosylceramide
Galactosylceramides - pharmacology
Galactosylceramides - therapeutic use
Gynecology
Heat shock proteins
Hospitals
Hyperthermia
Hyperthermia, Induced
Immune response
Immune system
Immunology
Inflammation
Inflammation Mediators - metabolism
Interferon
Ligands
Lymphocytes
Lymphocytes T
Medical research
Medicine
Metastasis
Mice
Natural killer cells
Obstetrics
Ovarian cancer
Ovarian carcinoma
Ovarian Neoplasms - drug therapy
Ovarian Neoplasms - pathology
Peritoneum
Peritoneum - drug effects
Peritoneum - pathology
Phagocytes
Phagocytosis - drug effects
T cell receptors
Th1 Cells - drug effects
Th1 Cells - metabolism
Th2 Cells - drug effects
Th2 Cells - metabolism
Toxicity
Tumor cell lines
Tumors
γ-Interferon
title Intra-peritoneal hyperthermia combining α-galactosylceramide in the treatment of ovarian cancer
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