Interstitial 5-ALA photodynamic therapy and glioblastoma: Preclinical model development and preliminary results

Tétard, Marie-Charlotte; Vermandel, Maximilien; Leroy, Henri‐Arthur; Leroux, B.; Maurage, Claude‐Alain; Lejeune, Jean‐Paul; Mordon, Serge; Reyns, Nicolas

doi:10.1016/j.pdpdt.2015.07.169

Cited by 35 publications

(36 citation statements)

References 43 publications

(74 reference statements)

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“…Therefore, our observation that PDT is able to induce necrosis in glioblastoma cells in vitro is quite unique and translates perfectly with in vivo observations showing important necrosis in treated tumors [23].…”

Section: Discussionsupporting

confidence: 85%

“…On the other hand, PDT is known to induce both necrosis and apoptosis in glioblastoma [19,20]. Recently, Receptor Interacting Protein kinase 3 (RIP3), a key protein of the programmed necrosis pathway (necroptosis) was demonstrated to be involved in PDT-induced glioblastoma cell death induced by PDT [21][22][23] and other cell death inducers [24][25][26]. The current model of necroptosis relies on the assembly of the "necrosome" complex, in which Receptor Interacting Protein kinase 3 (RIP3) interacts with RIP1, Fas-Associated protein with Death Domain (FADD) and Caspase-8 upon a combined treatment of TNF-α, Smac-mimetic and pan-caspases inhibitors [27].…”

Section: Introductionmentioning

confidence: 99%

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RIP3 antagonizes a TSC2-mediated pro-survival pathway in glioblastoma cell death

Fettweis¹,

Valentin

L’homme³

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Glioblastomas are the deadliest type of brain cancer and are frequently associated with poor prognosis and a high degree of recurrence despite removal by surgical resection and treatment by chemo-and radio-therapy. Photodynamic therapy (PDT) is a treatment well known to induce mainly necrotic and apoptotic cell death in solid tumors. 5-Aminolevulinic acid (5-ALA)-based PDT was recently shown to sensitize human glioblastoma cells (LN-18) to a RIP3 (Receptor Interacting Protein 3)-dependent cell death which is counter-acted by activation of autophagy. These promising results led us to investigate the pathways involved in cell death and survival mechanisms occurring in glioblastoma following PDT. In the present study, we describe a new TSC2 (Tuberous Sclerosis 2)-dependent survival pathway implicating MK2 (MAPKAPK2) kinase and 14-3-3 proteins which conducts to the activation of a pro-survival autophagy. Moreover, we characterized a new RIP3/TSC2 complex where RIP3 is suggested to promote cell death by targeting TSC2-dependent survival pathway. These results highlight (i) a new role of TSC2 to protect glioblastoma against PDT-induced cell death and (ii) TSC2 and 14-3-3 as new RIP3 partners.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

RIP3 antagonizes a TSC2-mediated pro-survival pathway in glioblastoma cell death

Fettweis¹,

Valentin

L’homme³

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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“…Also, the application of brain hypothermia is an established procedure in neurology . Apart from applying 100% oxygen breathing during PDT, it may be important to exploit preclinical observations of an improved tumor tissue response to PDT by fractionated irradiation . How tumor tissue phototoxicity might be enhanced by simply interrupting irradiation a few times for a few minutes only can be understood when looking at oxygen diffusion between capillaries during irradiation, resulting in a relative depletion of oxygen available for the cells furthest away from the next capillary .…”

Section: ‐Ala Based Photodynamic Therapy Of Malignant Gliomamentioning

confidence: 99%

5‐ALA in the management of malignant glioma

Stepp¹,

2018

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Background: Patients suffering from malignant gliomas have a poor prognosis. For the surgical treatment of these tumors, 5-aminolevulinic acid (5-ALA) has become a new standard. Aims: This review intends to provide an overview over current status, significance, limitations, and future perspectives of 5-ALA based fluorescence guided surgery and photodynamic therapy for brain tumor patients. Materials and Methods: From peer reviewed publications on the many aspects connected with this topic, those with potential clinical relevance were selected and put in the context of our own experience. Results and Discussion: The high tumor selectivity of accumulation of fluorescent protoporphyrin IX (PpIX) after systemic administration of 5-ALA enables intra-operative fluorescence guidance, which is unimpaired by brainshift and does not require expensive equipment. The neurosurgical aim of complete resection of enhancing tumor can now more easily be achieved, which improves prognosis in these patients. Nevertheless, despite better surgery tumors will inevitably recur. In order to further prolong survival, the phototoxic properties of PpIX are presently being exploited in clinical trials of post-operative or interstitial photodynamic therapy (PDT). Conclusion: 5-ALA based fluorescence guidance and PDT offer an intriguing new option for the management of malignant gliomas. Lasers Surg. Med. 50:399-419, 2018.

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“…Fractionation (i.e., alternating the on/off period of light) might address this issue . Accordingly, Tétard et al previously reported data suggesting an improvement in the PDT effect after fractionated PDT compared with continuous illumination .…”

Section: Introductionmentioning

confidence: 99%

MRI assessment of treatment delivery for interstitial photodynamic therapy of high‐grade glioma in a preclinical model

et al. 2017

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Ethical approval: This article contains studies using animals. All applicable institutional and national guidelines for the care and use of animals were followed. The experimental design was declared to the French National Ethics Committee under reference number 04870.01. Acknowledgments ObjectivesPrevious studies have reported the outcomes of PDT for glioblastoma via immunohistological data.Our study aimed to evaluate MRI findings, including diffusion and perfusion sequences, compared with immunohistological data from the same population to address the efficiency of light fractionation. Materials and MethodsTwenty-six "nude" rats grafted with human U87 cells into the right putamen underwent PDT. After PS precursor (5-ALA) intake, an optical fiber was introduced into the tumor. The rats were randomized into the following groups: those without illumination and those that received two or five fractions of light. Treatment effects were assessed with early high-field MRI to measure the volume of necrosis and edema using diffusion and perfusion sequences; the MRI results were compared with immunohistology results, including necrosis and apoptosis markers. ResultsElevated diffusion values were observed on MRI in the centers of the tumors of the treated animals, especially in the 5-fraction group (p < 0.01). Perfusion was decreased around the treatment site, especially in the 5-fraction group (p = 0.024). The MRI findings were consistent with previously published histological data. The median volume of necrosis was significantly different between the sham group and treated groups, 0 mm 3 vs. 2.67 mm 3 , p < 0.001. The same trend was previously observed in histology data when grading the absence or presence of necrosis and when the presence of necrosis was significantly more predominant for the treated group than for the untreated group (p < 001). Additionally, cell death represented by apoptosis marker data (TUNEL method) was significantly higher in the 5-fraction group than in the 2-fraction group (p = 0.01). ConclusionDiffusion and perfusion MRI revealed histological lesions. Interstitial PDT induced specific lesions in the tumor tissue, which were observed with MRI and confirmed by histopathological analysis. Thus, MRI may provide a non-invasive and reliable tool to assess treatment outcomes after PDT.

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Interstitial 5-ALA photodynamic therapy and glioblastoma: Preclinical model development and preliminary results

Cited by 35 publications

References 43 publications

RIP3 antagonizes a TSC2-mediated pro-survival pathway in glioblastoma cell death

RIP3 antagonizes a TSC2-mediated pro-survival pathway in glioblastoma cell death

5‐ALA in the management of malignant glioma

MRI assessment of treatment delivery for interstitial photodynamic therapy of high‐grade glioma in a preclinical model

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