Amfenac increases the radiosensitivity of uveal melanoma cell lines

Fernandes, Bruno F.; Marshall, J; Cesare, Sebastian Di; Logan, Patrick; Maloney, Shawn C.; Burnier, Miguel N.

doi:10.1038/sj.eye.6703042

Cited by 10 publications

(12 citation statements)

References 39 publications

(38 reference statements)

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“…However, some patients have to undergo subsequent enucleation because of radiotherapy-related complications. This situation has raised concerns on how to optimize the effectiveness of radiation treatment [6,7]. Therefore, knowledge of the factors that cause radioresistance is essential to optimize therapeutic strategies and prevent side effects.…”

Section: Discussionmentioning

confidence: 99%

“…However, after large-dose fraction irradiation treatment, up to 20% of patients undergo subsequent enucleation because of radiotherapy-related complications. This situation has raised concerns on how to optimize the effectiveness of radiation treatment [6,7]. Recent investigations of microRNAs (miRNAs), however, are changing our understanding of the tumor biology of UM and are helping us to identify novel targets for radiotherapy [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

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Let-7b overexpression leads to increased radiosensitivity of uveal melanoma cells

et al. 2015

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Uveal melanoma (UM) is an intraocular malignant tumor in adults that is characterized by rapid progression and recurrence. Irradiation has become the primary therapy for UM patients who are not candidates for surgery. However, after large-dose fraction irradiation treatment, some patients undergo subsequent enucleation because of radiotherapy-related complications. This situation has raised concerns on how to optimize the effectiveness of radiation treatment. Recent investigations of microRNAs are changing our understanding of UM tumor biology and are helping to identify novel targets for radiotherapy. The radioresistant UM cell lines OM431 and OCM1 were selected and exposed to irradiation, and let-7b was found to be downregulated after exposure. We then confirmed that let-7b mimics could inhibit UM growth both in vitro and in vivo. More specifically, transfection with let-7b mimics markedly resensitized OCM1 and OM431 cells to irradiation by reducing the population of S-phase cells. Cyclin D1 plays a vital role in cell cycle arrest, which is induced by let-7b overexpression. Cyclin D1 is also a target of let-7b and its expression is suppressed by upregulation of let-7b. Collectively, our results indicate that let-7b overexpression can in turn downregulate cyclin D1 expression and enhance the radiosensitivity of UM through cell cycle arrest. Let-7b could serve as a marker for radiosensitivity and could enhance the therapeutic benefit of UM cell irradiation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Let-7b overexpression leads to increased radiosensitivity of uveal melanoma cells

et al. 2015

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“…Barak et al102 demonstrated that serum VEGF increased significantly after metastatic development in UM patients and that it could serve as a biomarker for metastatic UM. Preclinical studies demonstrated that bevacizumab, a monoclonal anti-VEGF antibody, suppressed in vitro growth and in vivo hepatic micrometastasis of ocular melanoma cells 63. However, some in vitro studies have found paradoxical results, with an increase in tumor growth after bevacizumab treatment.…”

Section: Systemic Therapiesmentioning

confidence: 99%

Current and emerging treatment options for uveal melanoma

Pereira¹,

Odashiro²,

Lim³

et al. 2013

OPTH

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Uveal melanoma (UM) is the most common primary malignant intraocular tumor in adults, with a 10-year cumulative metastatic rate of 34%. The most common site of metastasis is the liver (95%). Unfortunately, the current treatment of metastatic UM is limited by the lack of effective systemic therapy. Options for the management of the primary intraocular tumor include radical surgery as well as conservative treatments in order to preserve visual acuity. For metastatic disease, several approaches have been described with no standard method. Nevertheless, median survival after liver metastasis is poor, being around 4–6 months, with a 1-year survival of 10%–15%. In this review, the authors summarize current and promising new treatments for UM.

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“…More recently, radiotherapy has become the primary therapy for UM patients who are not candidates for surgery, and more and more UM patients are being treated by radiation with radioactive plaques, charged particles, and photons (Gragoudas and Marie Lane, 2005; Mueller et al., 2000; Singh and Kivela, 2005). However, human UM cell lines display a wide range of radiosensitivity and some are relatively radioresistant (Fernandes et al., 2008; Logani et al., 1995a; Soulieres et al., 1995; Van Den Aardweg et al., 2002). This raises concerns about the effectiveness of this form of treatment.…”

Section: Introductionmentioning

confidence: 99%

Radiation‐inducible human tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) gene therapy: a novel treatment for radioresistant uveal melanoma

Zhou

Song

Jia

et al. 2010

Pigment Cell Melanoma Res

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SummaryUveal melanoma (UM) is one of the most therapy-resistant cancers. Radiotherapy is the preferred treatment for most cases of UM. However, some UM cells, such as the SP6.5 or OM431 cell lines, are relatively radioresistant. In this study, we attempted to improve the current UM therapy using an adenovirus radio-inducible gene therapy system. The antitumor adenovirus was constructed by inclusion of the radiation-inducible early growth response gene 1 (EGR1) promoter and the anticancer tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene. We demonstrated that the UM SP6.5 and OM431 cell lines were susceptible to the TRAIL-induced antitumor effect. TRAIL expression was enhanced in the adenovirus containing EGR1 ⁄ ⁄ TRAIL (Ad-ET) treatment group by radiotherapy, whereas Ad-ET significantly increased cell death and apoptosis caused by radiotherapy. In mice bearing xenograft tumors, apoptotic cells were detected in pathological tumor sections. Adenovirus Ad-ET combined with radiation therapy significantly inhibited tumor growth compared with the other treatment groups (P < 0.01). Our findings indicate that radioresponsive gene therapy has the potential to be a more effective and specific therapy for UM because the therapeutic gene can be spatially or temporally controlled by exogenous radiation.

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Amfenac increases the radiosensitivity of uveal melanoma cell lines

Cited by 10 publications

References 39 publications

Let-7b overexpression leads to increased radiosensitivity of uveal melanoma cells

Let-7b overexpression leads to increased radiosensitivity of uveal melanoma cells

Current and emerging treatment options for uveal melanoma

Radiation‐inducible human tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) gene therapy: a novel treatment for radioresistant uveal melanoma

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