Abscopal regression of hepatocellular carcinoma after radiotherapy for bone metastasis

Ohba, Kazuo; Omagari, Katsuhisa; Nakamura, Takashi; Ikuno, Nobuhiro; Saeki, Sachiko; Matsuo, Isao; Kinoshita, Hideki; Masuda, Junichi; Hazama, Hiroaki; Sakamoto, Ichiro; Kohno, Shigeru

doi:10.1136/gut.43.4.575

Cited by 255 publications

(188 citation statements)

References 16 publications

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“…He was the first to use the term 'abscopal effect,' where 'abscopal' is derived from the Latin prefix ab, meaning 'away from,' and the Greek word skopos, meaning 'target.' multiple case studies describing an abscopal effect observed after radiotherapy have been published for a variety of malignancies, including lymphoma, papillary adenocarcinoma, melanoma, adenocarcinoma of the esophagus, chronic lymphocytic leukemia and hepatocellular carcinoma (21)(22)(23)(24)(25).…”

Section: Discussionmentioning

confidence: 99%

Modulated electro-hyperthermia enhances dendritic cell therapy through an abscopal effect in mice

et al. 2014

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Abstract. The aim of this study was to assess whether modulated electro-hyperthermia (mEHT) can induce an abscopal effect and thereby enhance the antitumor effects of immunotherapy. We used an intratumoral dendritic cell (DC) injection and mEHT to treat C3H/He mice inoculated with squamous cell carcinoma SCCVII cells in the left leg, and we assessed the whole body antitumor effects. Tumors were examined every two or three days in order to assess growth inhibition. The tumor-draining lymph nodes were removed to enable flow cytometric analysis of CD3 + and CD8 + cells, whereas immunohistochemistry was used to assess CD8, S100 and Foxp3 expression in the tumors. Additionally, GP96 expression in the tumors from the different treatment groups was measured. In the control group, the mean tumor volume was larger than that in other groups. These results indicated that the combination therapy of an intratumoral DC injection and mEHT evoked systemic antitumor activity. A larger number of CD3 + and CD8 + cells were detected by flow cytometric analysis in the DC plus mEHT treatment group. Tumor tissue immunostaining showed that CD8 and S100 were more strongly expressed in the DC plus mEHT treatment group, although Foxp3 expression was much higher in the control group. The GP96 gene expression level in the mEHT group was significantly different from the expression level in the control group. An abscopal effect may be induced by mEHT, and the effect of immunotherapy with DCs was strongly enhanced by the overexpression of GP96. GP96 is thought to be one of the molecules explaining the abscopal effect. Direct intratumoral administration of DCs and mEHT may be a feasible future treatment strategy.

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Section: Discussionmentioning

confidence: 99%

Modulated electro-hyperthermia enhances dendritic cell therapy through an abscopal effect in mice

et al. 2014

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“…Oxidative-stress mediators have also been implicated in abscopal effects, whereby cytotoxic effects are observed in solid tumors located at distant sites from those targeted by radiation. It is thought that such effects are mediated by redox-sensitive cytokines that are cytotoxic (Ohba et al, 1998) or capable of mediating a systemic antitumor effect through the activation of immune activity (Uchida et al, 1989). Furthermore, genomic instability in the progeny of cells surviving a radiation exposure has been associated with intracellular oxidants, oxidative DNA base damage and vulnerability to free radical membrane damage (Clutton et al, 1996).…”

Section: Role Of Oxidative Metabolismmentioning

confidence: 99%

Oxidative metabolism, gap junctions and the ionizing radiation-induced bystander effect

2003

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Evidence accumulated over the past two decades has indicated that exposure of cell populations to ionizing radiation results in significant biological effects occurring in both the irradiated and nonirradiated cells in the population. This phenomenon, termed the 'bystander response', has been shown to occur both in vitro and in vivo and has been postulated to impact both the estimation of risks of exposure to low doses/low fluences of ionizing radiation and radiotherapy. Several mechanisms involving secreted soluble factors, oxidative metabolism and gapjunction intercellular communication have been proposed to regulate the radiation-induced bystander effect. Our current knowledge of the biochemical and molecular events involved in the latter two processes is reviewed in this article.

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“…Bystander effects require either direct cell-cell contact or the presence of soluble circulating factors that might contribute to a distant antitumor effect as demonstrated by medium transfer experiments. [9][10][11][12][13][14][15] At present there is no report of alkylating agent induction of such bystander effects. It is known that chloroethylnitrosourea (CENU) causes DNA damage.…”

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confidence: 99%

Bystander effects are induced by CENU treatment and associated with altered protein secretory activity of treated tumor cells A relay for chemotherapy?

Demidem

Morvan

Madelmont

2006

Intl Journal of Cancer

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In a previous study, it was reported that secondary untreated melanoma tumors implanted several weeks after and at distance from primary chloroethylnitrosourea (CENU)-treated tumors underwent differentiation and growth inhibition. To see whether the primary treated tumor released soluble factors that mediated the secondary tumor response, serum transfer experiments were performed in vivo. Administration of serum from CENU-treated tumor-bearing donors arrested tumor proliferation, decreased vessel formation and induced tumor metabolite alterations encompassing glutathione decrease and polyunsaturated fatty acid and phosphoethanolamine increase. These changes mimicked secondary tumor phenotype. To reproduce the model in vitro, cell culture supernatant transfer experiments were performed. CENU-treated cell cultures showed polyploidy and reactive oxygen species (ROS) production. Cell cultures challenged by a conditioned medium of CENU-treated cells underwent growth inhibition, cytoskeleton disorders, cytokinesis retardation, metabolite alterations, glutathione decrease and phosphoethanolamine increase, without ROS elicitation. Proteomics of CENU-treated cell conditioned media revealed altered protein secretion activity by CENU-treated cells. Among de novo secreted proteins, the most expressed were phosphatidylethanolamine-binding protein (PEBP), cardiovascular heat shock protein (cHsp), Rho-associated coiled-coil forming kinase 2 (ROCK) and actin fragments. These proteins testified of cytoskeleton disorders, growth inhibition and metabolite alterations. This article demonstrates the release by CENU-treated tumors of growth inhibitory differentiation-inducing soluble factors. These factors mediate remote bystander effects and attest persistent biological activity of residual tumors after chemotherapy. ' 2006 Wiley-Liss, Inc.Key words: chloroethylnitrosoureas; distant double tumor models; growth inhibition; bystander effects; proteomics There is increasing experimental evidence that therapy-induced tumor cell modification (cell-based gene and ionizing radiation therapies) may promote the immune system or induce the expression of cytokines or other factors that may be inhibitory for local or distant unmodified tumor cells. [1][2][3][4][5][6][7][8] Cell-based gene therapy after cytokine or suicide gene transfer has been investigated for autologous and allogeneic vaccination in cancer therapy. Tumor cells engineered to produce cytokines such as interleukin-12 (IL-12) induced antitumor immunity capable of inhibiting a challenge with unmodified parental tumor cells.1 Recently, in a model of allogeneic tumor cells transduced with IL-12 mixed with autologous lymphoma cells, IL-12 induced microenvironmental changes that, through the induction of an immune response, yielded eradication of distant preestablished lymphoma.2 Cells transfected with a suicide gene such as that of thymidine kinase from herpes simplex virus 3-6 or of cytosine desaminase, 7-8 enzymes that activate a drug or prodrug, inhibited distant tumors and provok...

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Abscopal regression of hepatocellular carcinoma after radiotherapy for bone metastasis

Cited by 255 publications

References 16 publications

Modulated electro-hyperthermia enhances dendritic cell therapy through an abscopal effect in mice

Modulated electro-hyperthermia enhances dendritic cell therapy through an abscopal effect in mice

Oxidative metabolism, gap junctions and the ionizing radiation-induced bystander effect

Bystander effects are induced by CENU treatment and associated with altered protein secretory activity of treated tumor cells A relay for chemotherapy?

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