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      Cytotoxicity on low-grade canine meningioma with the use of somatostatin analog (octreotide): An in vitro study

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          Abstract

          Background

          Meningioma is the most common tumor of the central nervous system of dogs. For this tumor, surgery remains the treatment of choice, either alone or in combination with radiotherapy. Unfortunately, chemotherapeutic strategies are practically absent in dogs and palliative therapies are the only option to surgery. Somatostatin receptor subtype 2 (SSTR2) is expressed in canine meningioma. Since the potent cell-proliferation inhibiting effect of somatostatin (SST), the aim of this study was to investigate in vitro the effects of octreotide, as SST analog, in the viability of canine meningioma.

          Methods

          Four surgical canine meningiomas were used in this study to establish cell cultures. Expression of SSTR2 was verified with immunolabelling in FFPE samples and cell cultures. The effects of octreotide on cell viability were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT). After 24 hours they were exposed to different concentrations of octreotide (0.1 nM, 1 nM, 10 nM, 100 nM) for 24 and 48 hours.

          Results

          All meningiomas consisted of grade I tumors. The cultured neoplastic cells expressed SSTR2 from 80% to 100%. Octreotide significantly increased cell death after 48 hours of continuous exposure, with 10 and 100 nM octreotide doses. The percentage of cell viability was 80.92 ± 4.9 and 80.49 ± 3.61, compared to the control, respectively, consistent with decreased cell viability of about 20% for both doses.

          Conclusions

          Octreotide reduced the alive neoplastic cultured cells of low-grade canine meningioma in a dose-dependent pattern with continuous exposition for 48 hours. These results support an alternative systemic treatment of meningioma with octreotide in the dog.

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          Most cited references29

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          EANO guideline on the diagnosis and management of meningiomas

          Meningiomas are the most common intracranial tumors. Yet, only few controlled clinical trials have been conducted to guide clinical decision making, resulting in variations of management approaches across countries and centers. However, recent advances in molecular genetics and clinical trial results help to refine the diagnostic and therapeutic approach to meningioma. Accordingly, the European Association of Neuro-Oncology (EANO) updated its recommendations for the diagnosis and treatment of meningiomas. A provisional diagnosis of meningioma is typically made by neuroimaging, mostly magnetic resonance imaging. Such provisional diagnoses may be made incidentally. Accordingly, a significant proportion of meningiomas, notably in patients that are asymptomatic or elderly or both, may be managed by a watch-and-scan strategy. A surgical intervention with tissue, commonly with the goal of gross total resection, is required for the definitive diagnosis according to the WHO classification. A role for molecular profiling including gene panel sequencing and genomic methylation profiling is emerging. A gross total surgical resection including the involved dura is often curative. Inoperable or recurrent tumors requiring treatment can be treated with radiosurgery, if the size or the vicinity of critical structures allows that, or with fractionated radiotherapy (RT). Treatment concepts combining surgery and radiosurgery or fractionated RT are increasingly used, although there remain controversies regard timing, type, and dosing of the various RT approaches. Radionuclide therapy targeting somatostatin receptors is an experimental approach, as are all approaches of systemic pharmacotherapy. The best albeit modest results with pharmacotherapy have been obtained with bevacizumab or multikinase inhibitors targeting vascular endothelial growth factor receptor, but no standard of care systemic treatment has been yet defined.
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            Next Generation CAR T Cells for the Immunotherapy of High-Grade Glioma

            High grade gliomas (HGG) comprise a heterogeneous group of brain malignancies with dismal prognosis. Current standard-of-care includes radiation, chemotherapy, and surgical resection when possible. Despite advances in each of these treatment modalities, survival rates for pediatric and adult HGG patients has remained largely unchanged over the course of several years. This is in stark contrast to the significant survival increases seen recently for a variety of hematological and other solid malignancies. The introduction and widespread use of immunotherapies have contributed significantly to these survival increases, and as such these therapies have been explored for use in the treatment of HGG. In particular, chimeric antigen receptor (CAR) T cell therapy has shown promise in clinical trials in HGG patients. However, unlike the tremendous success CAR T cell therapy has seen in B cell leukemia and lymphoma treatment, the success in HGG patients has been modest at best. This is largely due to the unique tumor microenvironment in the central nervous system, difficulty in accessing the tumor site, and heterogeneity in target antigen expression. The results of these features are poor CAR T cell proliferation, poor persistence, suboptimal cytokine secretion, and the emergence of antigen-loss tumor variants. These issues have called for the development of “next generation” CAR T cells designed to circumvent the barriers that have limited the success of current CAR T cell technologies in HGG treatment. Rapid advancements in gene editing technologies have provided several avenues for CAR T cell modification to enhance their efficacy. Among these are cytokine overexpression, gene knock-out and knock-in, targeting of multiple antigens simultaneously, and precise control of CAR expression and signaling. These “next generation” CAR T cells have shown promising results in pre-clinical models and may be the key to harnessing the full potential of CAR T cells in the treatment of HGG.
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              Everolimus and Octreotide for Patients with Recurrent Meningioma: Results from the Phase II CEVOREM Trial

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                Author and article information

                Contributors
                Journal
                Neurooncol Adv
                Neurooncol Adv
                noa
                Neuro-Oncology Advances
                Oxford University Press (US )
                2632-2498
                Jan-Dec 2024
                02 July 2024
                02 July 2024
                : 6
                : 1
                : vdae111
                Affiliations
                Department of Veterinary Medicine, University of Perugia, Perugia (IT)
                Department of Veterinary Medicine, University of Perugia, Perugia (IT)
                Department of Veterinary Medicine, University of Perugia, Perugia (IT)
                Clinica Veterinaria Valdinievole, Monsummano Terme (IT)
                Clinica Veterinaria Pedrani - Diagnostica Piccoli Animali , Zugliano (IT)
                Polo Neurologico Veterinario , San Marino (RSM)
                Department of Veterinary Medicine, University of Perugia, Perugia (IT)
                Author notes
                Corresponding Author: Maria Teresa Mandara, DVM, Laboratory of Neuropathology, Department of Veterinary Medicine, University of Perugia (IT), Via S. Costanzo 4, 06126, Perugia (IT) ( mandara@ 123456unipg.it ).
                Author information
                https://orcid.org/0000-0003-1501-6163
                Article
                vdae111
                10.1093/noajnl/vdae111
                11272066
                39055601
                0f2dbe29-48ce-4ef2-bc52-c1340d61e14e
                © The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 July 2024
                Page count
                Pages: 7
                Funding
                Funded by: University of Perugia, DOI 10.13039/501100010607;
                Categories
                Basic and Translational Investigations
                AcademicSubjects/MED00300
                AcademicSubjects/MED00310

                chemotherapy,dog,meningioma,octreotide,somatostatin
                chemotherapy, dog, meningioma, octreotide, somatostatin

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