Modulation of cisplatin cytotoxicity by human recombinant interferon-γ in human ovarian cancer cell lines

Nehmé, Alissar; Julia, Anne Marie; Jozan, S.; Chevreau, C.; Bugat, R.; Canal, Pierre

doi:10.1016/0959-8049(94)90430-8

Cited by 22 publications

(6 citation statements)

References 14 publications

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“…IFNs have previously been shown to potentiate the cytotoxic effect of all chemicals tested in this study: HU [32,33], 5-FU [34,35], MTX [36] and cisPt [37,38]. Yonekura et al [39] have even proposed that Hsp27 plays a crucial role in the IFN-γ-induced sensitization of oral squamous cell carcinoma cells to anticancer drugs.…”

Section: Discussionmentioning

confidence: 99%

Antitumor Activity from the Combined Application of Poly(I:C) and Chemotherapeutics in Human Metastatic Pharyngeal Cell Lines

Matijević¹,

Kirinec²,

Pavelić³

2011

Chemotherapy

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Background: Toll-like receptor 3 (TLR3) activation in tumor cells induces apoptosis. We investigated the effect of TLR3 ligand (poly(I:C)) in combination with chemotherapeutics applied to human pharyngeal carcinoma cells as a possible antitumor therapy. Methods:Human pharyngeal cancer cell lines were studied (FaDu and Detroit 562). Cytotoxicity assays and apoptosis assays (annexin V staining and caspase 3/7 activity measurements) were used to investigate the cytotoxic effects. By using TLR3 siRNA we confirmed that the observed effect is TLR3-dependent. Results: We found that the combined application of poly(I:C) and chemotherapeutics (cisPt, HU, 5-FU and MTX) has a stronger inhibitory effect on cell growth in tumor cells expressing functional TLR3 as compared with a single treatment. This is a result of TLR3-dependent apoptosis. Conclusion: Our study showed that a combined application of the two agents already being used in tumor therapy could lower the necessary dosage of chemotherapeutics, leading to fewer side effects.

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Section: Discussionmentioning

confidence: 99%

Antitumor Activity from the Combined Application of Poly(I:C) and Chemotherapeutics in Human Metastatic Pharyngeal Cell Lines

Matijević¹,

Kirinec²,

Pavelić³

2011

Chemotherapy

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“…Immunostimulants such as interleukins, tumor necrosis factor (TNF), and interferon (IFN) have potent antitumoral activities, alone or in combination with cisplatin. 4,5 We demonstrated previously that an aggressive syngeneic murine ovarian carcinoma was completely treated with the cisplatinbased lipofection of IFN-␥ gene through enhanced long-lasting production of IFN-␥ only in tumor localized sites, which was prevented by the inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine. 6 To expand this observation, we have determined whether a combination therapy of cisplatin and cationic liposomes containing an expression vector for IFN-␥ is effective in iNOS knockout (iNOSKO) mice, which are unable to produce NO in response to IFN-␥.…”

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confidence: 99%

Nitric oxide-mediated tumor cell killing of cisplatin-based interferon-γ gene therapy in murine ovarian carcinoma

Son

Hall

2000

Cancer Gene Ther

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We have determined the role of nitric oxide (NO)-mediated tumor cell killing in the treatment of an animal model of murine ovarian carcinoma grown in the peritoneum with a combination of cisplatin and cationic liposomes containing an expression vector for interferon-␥ (IFN-␥). The approach was to determine whether the therapy was effective in mice homozygous for a disrupted inducible NO synthase (iNOS) allele; these mice were unable to produce NO in response to IFN-␥. iNOS (Ϫ/Ϫ) mice treated with both cisplatin and liposomal IFN-␥ gene did not produce a significant amount of NO in ascites (12.1 Ϯ 4.5 M), although they expressed a high level of IFN-␥ (9002 Ϯ 723 U/mL of ascitic fluid). As a result, mice died of tumors within 11-62 days. However, wild-type mice treated with both cisplatin and liposomal IFN-␥ gene produced a significant amount of NO in ascites (113.7 Ϯ 17.9 M) with a high level of IFN-␥ gene expression (9350 Ϯ 1254 U/mL of ascitic fluid) and were free of tumors for at least 80 days. This result confirmed that NO was a direct mediator of IFN-␥ cytotoxicity.

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“…Studies have shown that, in vitro, IFNg may act synergistically with platinum-based chemotherapy to promote apoptosis and inhibition of proliferation, possibly through the mechanisms described previously (16). The use of IFNg in a clinical setting is still being evaluated (17), although improvements in progression-free survival have already been seen (18).…”

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confidence: 99%

Loss of IFNγ Receptor Is an Independent Prognostic Factor in Ovarian Cancer

Duncan

Rolland

Deen³

et al. 2007

Clinical Cancer Research

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Purpose: There is evidence that IFNg plays an important role in ovarian cancer development.IFNg produces numerous antitumor effects and it may be evasion of these effects which allows tumor progression. We postulate that genetic instability in tumor cells may lead to modulation of expression of the IFNg receptor, thus leading to altered tumor biology and patient prognosis.This hypothesis would support the theory of immunoediting in ovarian cancer. Experimental Design: Using tissue microarray technology of 339 primary ovarian cancers, the expression of IFNg receptor was assessed immunohistochemically. Coupled to a comprehensive database of clinicopathologic variables, its effect on these factors was studied. Results: Tumors expressing high levels of IFNg receptor had significantly improved survival (P = 0.017) compared with tumors expressing low levels of the receptor; this was also seen with complete receptor loss (P = 0.014). Factors shown to predict prognosis independently of each other were the following: age, International Federation of Gynecologists and Obstetricians stage, and the absence of macroscopic disease after surgery.The level of IFNg receptor expression and complete receptor loss were independently predictive of prognosis on multivariate analysis.There was no correlation between receptor status and any of the standard clinicopathologic variables. Conclusions: Loss of IFNg receptor independently predicts poor prognosis in ovarian cancer. Loss of receptor expression may be responsible for the limited success in the therapeutic use of IFNg in ovarian cancer trials and highlights a subgroup of high expressing IFNg receptor tumors which are more likely to be susceptible to such treatments.

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Modulation of cisplatin cytotoxicity by human recombinant interferon-γ in human ovarian cancer cell lines

Cited by 22 publications

References 14 publications

Antitumor Activity from the Combined Application of Poly(I:C) and Chemotherapeutics in Human Metastatic Pharyngeal Cell Lines

Antitumor Activity from the Combined Application of Poly(I:C) and Chemotherapeutics in Human Metastatic Pharyngeal Cell Lines

Nitric oxide-mediated tumor cell killing of cisplatin-based interferon-γ gene therapy in murine ovarian carcinoma

Loss of IFNγ Receptor Is an Independent Prognostic Factor in Ovarian Cancer

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