Controlled clinical trial of interferon-gamma as postoperative surgical adjuvant therapy for colon cancer.

Wiesenfeld, Martin; O'Connell, M. J.; Wieand, Harry S.; Gonchoroff, Nick J.; Donohue, John H.; Fitzgibbons, Robert J.; Krook, James E.; Mailliard, James A.; Gerstner, James B.; Pazdur, Richard

doi:10.1200/jco.1995.13.9.2324

Cited by 56 publications

(31 citation statements)

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“…In contrast, IFNg treatment did not result in any difference in the outcomes of patients with metastatic renal cell carcinomas (20). No clinically meaningful benefit was observed in a controlled trial testing the use of IFNg as a postoperative surgical adjuvant therapy for colon cancer (21). Furthermore, a phase III trial of IFNg plus carboplatin/paclitaxel versus carboplatin/paclitaxel alone for treating advanced ovarian carcinomas was stopped early due to the significantly shorter overall survival (OS) time of the patients receiving IFNg (22).…”

Section: Inconsistent Clinical Results Regarding the Effects Of Ifngmentioning

confidence: 93%

Dual Faces of IFNγ in Cancer Progression: A Role of PD-L1 Induction in the Determination of Pro- and Antitumor Immunity

Mandai

Hamanishi

Abiko

et al. 2016

Clinical Cancer Research

317

277

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Section: Inconsistent Clinical Results Regarding the Effects Of Ifngmentioning

confidence: 93%

Dual Faces of IFNγ in Cancer Progression: A Role of PD-L1 Induction in the Determination of Pro- and Antitumor Immunity

Mandai

Hamanishi

Abiko

et al. 2016

Clinical Cancer Research

317

277

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“…12 The role of adjuvant treatment in the therapy of colon carcinoma is an area of intense investigation and there is controversy on the benefit of IFN-gamma treatment. 39 However, several groups reported effectiveness of IFN-gamma against colon carcinoma cells in vitro and in vivo. [40][41][42][43] It may be speculated that the correlation of IFN effects and MTAP expression found in vitro in colon carcinoma cells could also have impact on the therapeutically success in vivo and may eventually allow to predict the tumour response to IFN treatment.…”

Section: Discussionmentioning

confidence: 99%

Strong expression of methylthioadenosine phosphorylase (MTAP) in human colon carcinoma cells is regulated by TCF1/[beta]-catenin

Bataille

Rogler

Modes

et al. 2005

Laboratory Investigation

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Methylthioadenosine phosphorylase (MTAP) is known as a ubiquitously expressed house keeping gene important in biochemical salvage processes. The MTAP gene is localized on the human chromosomal region 9p21, a region often deleted in cancer. Recently, several groups including our own have shown that MTAP serves as a tumour suppressor gene. The aim of this study was to analyse the role of MTAP in colon carcinoma and normal colon epithelium and the regulation of gene expression. To examine MTAP RNA and protein expression, we screened six colon carcinoma cell lines and human primary colon epithelial cells by RT-PCR and immunoblotting. MTAP expression was confirmed in vivo by immunohistochemical staining of normal colon tissue compared to adenoma and colon carcinoma. Interestingly, we found strong MTAP mRNA and protein expression by colon carcinoma cell lines but no expression by colonic epithelial cells. To analyse the regulation of MTAP expression, promoter studies were performed and revealed control of MTAP expression by LEF/TCF/bcatenin. Furthermore, we demonstrated a significant correlation between MTAP protein expression and tumour progression as the intensity of MTAP protein staining increased from normal tissue to carcinoma. In addition, the recently postulated association between MTAP activity and interferon (IFN) sensitivity was confirmed in colon epithelial cells showing only little response to IFN-gamma, in contrast to the carcinoma cell lines. In summary, these data indicate for the first time that MTAP is not expressed in normal human colonic epithelium but is strongly upregulated in colon carcinoma. This finding may be of clinical significance concerning the homeostasis of normal colon epithelium and potential treatment of colon carcinoma. Laboratory Investigation ( 2.28) plays a major role in polyamine metabolism and is important for the salvage of both adenine and methionine. MTAP catalyses the phosphorylation of methylthioadenosine (MTA), a by-product of the synthesis of polyamines, which acts as a potent inhibitor of polyamine aminopropyltransferase and methyltransferases. MTAP has been shown previously to be expressed abundantly in normal cells and tissues. 1 In contrast, many malignant cells lack MTAP activity, 2-5 and cultured MTAP-deficient cells secrete MTA instead of metabolising it. 6 The reason for the frequent loss of MTAP activity became evident after determining the chromosomal location of MTAP. Starting from the centromeric end, the gene order on human chromosome 9p21 was mapped as p15-p16-MTAP-interferon(IFN)-alpha-IFNbeta. 1 In this region, many tumours reveal selective deletions. Recently, MTAP gene deletions were described in endometrial cancer, osteosarcoma and in haematological neoplasias like lymphoblastic leukaemia or non-Hodgkin's lymphomas. [2][3][4][5] In addition to its role in polyamine metabolism, MTAP expression has recently been shown to have significant impact on signal transducer and activator of transcription (STAT) 1 activity. 7 STAT1 is

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“…There are conflicting reports in the surgical literature on the effect of post-operative IFN-γ administration. In patients with colonic cancer IFN-γ appears to increase HLA-DR expression on PBMCs, 29 whereas in other patients undergoing gastrointestinal surgery IFN-γ administered as part of in vitro experiments failed to reconstitute defective pro-inflammatory cytokine production. 29 Our data demonstrates that the in vitro administration of IFN-γ can reverse features of defective antigen presenting capacity following major surgery in patients both with and without cancer.…”

Section: Discussionmentioning

confidence: 96%

“…In patients with colonic cancer IFN-γ appears to increase HLA-DR expression on PBMCs, 29 whereas in other patients undergoing gastrointestinal surgery IFN-γ administered as part of in vitro experiments failed to reconstitute defective pro-inflammatory cytokine production. 29 Our data demonstrates that the in vitro administration of IFN-γ can reverse features of defective antigen presenting capacity following major surgery in patients both with and without cancer. Our use of a wellvalidated, standardized biomarker of immune suppression (mHLA-DR) of particular relevance in the prediction of septic complications enhances the potential clinical applicability of these results.…”

Section: Discussionmentioning

confidence: 96%

Features of Postoperative Immune Suppression Are Reversible With Interferon Gamma and Independent of Interleukin-6 Pathways

et al. 2016

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Controlled clinical trial of interferon-gamma as postoperative surgical adjuvant therapy for colon cancer.

Cited by 56 publications

References 0 publications

Dual Faces of IFNγ in Cancer Progression: A Role of PD-L1 Induction in the Determination of Pro- and Antitumor Immunity

Dual Faces of IFNγ in Cancer Progression: A Role of PD-L1 Induction in the Determination of Pro- and Antitumor Immunity

Strong expression of methylthioadenosine phosphorylase (MTAP) in human colon carcinoma cells is regulated by TCF1/[beta]-catenin

Features of Postoperative Immune Suppression Are Reversible With Interferon Gamma and Independent of Interleukin-6 Pathways

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