CNS Oncology最新文献

{"title":"Robot technology identifies a Parkinsonian therapeutics repurpose to target stem cells of glioblastoma.","authors":"Andres Vargas-Toscano,&nbsp;Dilaware Khan,&nbsp;Ann-Christin Nickel,&nbsp;Michael Hewera,&nbsp;Marcel Alexander Kamp,&nbsp;Igor Fischer,&nbsp;Hans-Jakob Steiger,&nbsp;Wei Zhang,&nbsp;Sajjad Muhammad,&nbsp;Daniel Hänggi,&nbsp;Ulf Dietrich Kahlert","doi":"10.2217/cns-2020-0004","DOIUrl":"https://doi.org/10.2217/cns-2020-0004","url":null,"abstract":"<p><p><b>Aim:</b> Glioblastoma is a heterogeneous lethal disease, regulated by a stem-cell hierarchy and the neurotransmitter microenvironment. The identification of chemotherapies targeting individual cancer stem cells is a clinical need. <b>Methodology:</b> A robotic workstation was programmed to perform a drug concentration to cell-growth analysis on an <i>in vitro</i> model of glioblastoma stem cells (GSCs). Mode-of-action analysis of the selected top substance was performed with manual repetition assays and acquisition of further parameters. <b>Results:</b> We identified 22 therapeutic potential substances. Three suggested a repurpose potential of neurotransmitter signal-modulating agents to target GSCs, out of which the Parkinson's therapeutic trihexyphenidyl was most effective. Manual repetition assays and initial mode of action characterization revealed suppression of cell proliferation, cell cycle and survival. <b>Conclusion:</b> Anti-neurotransmitter signaling directed therapy has potential to target GSCs. We established a drug testing facility that is able to define a mid-scale chemo responsome of <i>in vitro</i> cancer models, possibly also suitable for other cell systems.</p>","PeriodicalId":10469,"journal":{"name":"CNS Oncology","volume":"9 2","pages":"CNS58"},"PeriodicalIF":0.0,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/cns-2020-0004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37985211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retention rates of antiepileptic drugs in glioma patients: the most appropriate outcome.","authors":"Pim B van der Meer,&nbsp;Linda Dirven,&nbsp;Marta Fiocco,&nbsp;Martin Jb Taphoorn,&nbsp;Johan Af Koekkoek","doi":"10.2217/cns-2020-0009","DOIUrl":"https://doi.org/10.2217/cns-2020-0009","url":null,"abstract":"Pim B van der Meer*,1, Linda Dirven1,2, Marta Fiocco3,4, Martin JB Taphoorn1,2 & Johan AF Koekkoek1,2 1Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands 2Department of Neurology, Haaglanden Medical Center, The Hague, The Netherlands 3Department of Biomedical Data Sciences, Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands 4Mathematical Institute, Leiden University, Leiden, The Netherlands *Author for correspondence: Tel.: +31 71 526 2192; Fax: +31 71 524 8253; pbvandermeer@lumc.nl","PeriodicalId":10469,"journal":{"name":"CNS Oncology","volume":"9 2","pages":"CNS53"},"PeriodicalIF":0.0,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/cns-2020-0009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38099916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dural-based atypical teratoid/rhabdoid tumor in an adult: DNA methylation profiling as a tool for the diagnosis.","authors":"Hiba Alzoubi,&nbsp;Francesca Gianno,&nbsp;Felice Giangaspero,&nbsp;Daniela Bartolini,&nbsp;Luca Riccioni,&nbsp;Evelina Miele,&nbsp;Manila Antonelli","doi":"10.2217/cns-2020-0006","DOIUrl":"https://doi.org/10.2217/cns-2020-0006","url":null,"abstract":"<p><p>Atypical teratoid/rhabdoid tumor (ATRT) is a malignant CNS embryonal tumor that mostly occurs in childhood, adult cases are rare. We report a case of a 23-year-old male with an extra-axial dura-based lesion in the left frontal area, previously diagnosed as gliosarcoma. After 6 years, the patient had a recurrence and the previous slides were reviewed. Tumor was positive for vimentin and negative for INI1. The differential diagnosis for this extra-axial tumor with long survival was rhabdoid meningioma with INI1 loss or ATRT. DNA methylation profiling was performed to reach the final and the most definitive diagnosis; the result was ATRT. Our case suggests the usefulness of DNA methylation profiling for diagnosing challenging CNS tumors.</p>","PeriodicalId":10469,"journal":{"name":"CNS Oncology","volume":"9 2","pages":"CNS54"},"PeriodicalIF":0.0,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/cns-2020-0006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38102006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glioma induced alterations in fecal short-chain fatty acids and neurotransmitters.","authors":"Antonio Dono,&nbsp;Anthony Patrizz,&nbsp;Ryan M McCormack,&nbsp;Nagireddy Putluri,&nbsp;Bhanu P Ganesh,&nbsp;Balveen Kaur,&nbsp;Louise D McCullough,&nbsp;Leomar Y Ballester,&nbsp;Yoshua Esquenazi","doi":"10.2217/cns-2020-0007","DOIUrl":"https://doi.org/10.2217/cns-2020-0007","url":null,"abstract":"<p><p><b>Aim:</b> To explore fecal short-chain fatty acids and neurotransmitter alterations in a mouse-glioma model and glioma patients. <b>Methods:</b> Liquid chromatography-mass spectrometry and 16S rRNA-sequencing from fecal samples were performed to measure metabolite levels and taxa abundance in mice/humans. Mice underwent GL261 implantation with/without temozolomide. Glioma patients were compared with healthy controls. <b>Results:</b> Glioma altered several short-chain fatty acids and neurotransmitter levels. Reduced 5-hydroxyindoleaceic acid and norepinephrine levels were seen in mice and humans. Interestingly, temozolomide treatment abrogates the effects of glioma on fecal metabolites. <b>Conclusion:</b> Our findings demonstrate the interplay between glioma and the gut-brain axis. Further work is required to identify pathways within the gut-brain axis by which glioma influences and promotes the modulation of fecal metabolites and microbiome.</p>","PeriodicalId":10469,"journal":{"name":"CNS Oncology","volume":"9 2","pages":"CNS57"},"PeriodicalIF":0.0,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/cns-2020-0007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38102007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiologic and histologic characteristics of CNS lesions: a 20-year experience of a tertiary center in Lebanon.","authors":"Roland Eid,&nbsp;Stephanie Hage,&nbsp;Ingrid Antonios,&nbsp;Rita Moussa,&nbsp;Makram Khoury,&nbsp;Fady Ghassan Haddad,&nbsp;Hampig Raphael Kourie,&nbsp;Carole Kesrouani,&nbsp;Claude Ghorra,&nbsp;Gerard Abadjian,&nbsp;Joseph Kattan","doi":"10.2217/cns-2020-0001","DOIUrl":"https://doi.org/10.2217/cns-2020-0001","url":null,"abstract":"<p><p><b>Aim:</b> Report the epidemiologic and histologic characteristics of CNS lesions in the Lebanese population. <b>Methods:</b> We conducted a retrospective study evaluating 2025 CNS lesions diagnosed between 1998 and 2017 in the pathology laboratory of a Lebanese tertiary center. <b>Results:</b> 52.2% of patients were men with a median age of 50 years. The most frequent symptoms were epilepsy (22.5%), headache (20.6%) and motor impairment (19.9%). 90.7% of tumors were primary. Lung (35.6%) and breast (16.5%) were the most frequent primaries of metastases. 46.2% of primary CNS tumors were glial, predominantly astrocytic (56.4%), and (42.5%) were nonglial, predominantly meningeal tumors (58%). <b>Conclusion:</b> Compared with Western literature, the Lebanese population is characterized by a younger age of onset of brain tumors, a lower rate of meningiomas and a higher rate of gliomas.</p>","PeriodicalId":10469,"journal":{"name":"CNS Oncology","volume":"9 2","pages":"CNS55"},"PeriodicalIF":0.0,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/cns-2020-0001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38100441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disparities in patient enrollment on glioblastoma clinical trials.","authors":"Yang Liu,&nbsp;Andrea Wasilewski,&nbsp;Nimish A Mohile","doi":"10.2217/cns-2020-0008","DOIUrl":"https://doi.org/10.2217/cns-2020-0008","url":null,"abstract":"<p><p><b>Aim:</b> To determine if enrollment on glioblastoma (GBM) interventional clinical trials (ICTs) in the USA is representative of the population. <b>Materials & methods:</b> We queried ClinicalTrials.gov for all ICTs in GBM from 1994 to 2019. Demographics were obtained from ClinicalTrials.gov or the trial publication and compared with population data from Central Brain Tumor Registry of the United States. <b>Results:</b> In total, 10617 GBM patients were enrolled in 118 adult ICTs: median age was 54.0 (10.05 years younger than Central Brain Tumor Registry of the United States). Age was most discrepant in recurrent tumors, nonrandomized trials and consortium studies. Median age improved from 52.0 to 59.5 over 25 years. Women represented 37.5% of subjects. <b>Conclusion:</b> GBM ICTs under-represent older patients but representation of women reflects the population. ICTs need to be designed to better represent the population.</p>","PeriodicalId":10469,"journal":{"name":"CNS Oncology","volume":"9 2","pages":"CNS59"},"PeriodicalIF":0.0,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/cns-2020-0008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38099876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ibrutinib in primary central nervous system diffuse large B-cell lymphoma.","authors":"Justin T Low,&nbsp;Katherine B Peters","doi":"10.2217/cns-2019-0022","DOIUrl":"https://doi.org/10.2217/cns-2019-0022","url":null,"abstract":"<p><p>The standard regimen for the treatment of newly diagnosed primary CNS lymphoma (PCNSL) remains regimens that contain high-dose methotrexate (MTX). While these regimens can provide control for some patients, there is a dearth of options for the treatment of patients with PCNSL who cannot tolerate MTX-containing regimens, or whose cancers are refractory to MTX. In this article, we review a promising new option; ibrutinib, a Bruton tyrosine kinase inhibitor, for patients with relapsed and refractory PCNSL.</p>","PeriodicalId":10469,"journal":{"name":"CNS Oncology","volume":"9 1","pages":"CNS51"},"PeriodicalIF":0.0,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/cns-2019-0022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37711876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Welcome to Volume 9 of <i>CNS Oncology</i>.","authors":"Jennifer Straiton","doi":"10.2217/cns-2019-0023","DOIUrl":"https://doi.org/10.2217/cns-2019-0023","url":null,"abstract":"Content highlights Our most-read article of the year comes from Ugonma Chukwueke and Patrick Wen, both of the Dana-Farber Cancer Institute (MA, USA), and reviews the recommendations of the Response Assessment in Neuro-Oncology (RANO) working groups [1]. Distinct RANO groups have been set up for different tumor and treatment types, each group aiming to develop relevant and reliable criteria that can be implemented by clinicians. This review discusses how the recommendations given by the RANO groups may be applied to the care of patients with different brain tumor types and suggests what is still needed for the guidelines to fully reflect the complex nature of each tumor. For anyone interested in neuro-oncology and CNS oncology management, this is a key read. From Issue 1 of this volume, the article has been cited twice and is already the most-read article ever published in CNS Oncology. Next up, we have a preliminary communication written by David E Piccioni et al. (University of California San Diego, CA, USA), describing their study evaluating whether circulating tumor DNA could facilitate genomic interrogation in patients with primary brain tumors [2]. Contrary to previous studies in this area, the group found that 50% of patients included in the study had detectable circulating tumor DNA, making it a clinically viable option for analysis when identifying genomics-based therapy options. Another 2019 article that has hit our most-read list is an editorial that evaluates the benefits of whole-brain radiation therapy versus stereotactic radiosurgery for the treatment of brain metastases [3]. Written by a group from the City of Hope National Medical Center (CA, USA), the article discusses the shift in clinical practice from using whole-brain radiation therapy to stereotactic radiosurgery and looks to the future of radiation therapy for brain metastases. Finally, we have a set of three articles each discussing the Nativis Voyager R ©, an investigational therapeutic medical device that is being developed for the treatment of both pediatric and adult glioblastoma. With feasibility studies in both American [4] and Australian [5] populations, the researchers found no adverse events that could lead to the discontinuation of the device, and it demonstrated a benign safety profile. However, as stated in an editorial on the device by Victor Levin (MD Anderson, TX, USA), further studies are needed to determine the full impact of the therapy on overall survival of patients with glioblastoma [6].","PeriodicalId":10469,"journal":{"name":"CNS Oncology","volume":"9 1","pages":"CNS49"},"PeriodicalIF":0.0,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/cns-2019-0023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37694637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical response to pazopanib in a patient with endolymphatic sac tumor not associated with von Hippel-Lindau syndrome.","authors":"Thomas Nelson,&nbsp;Jethro Hu,&nbsp;Serguei Bannykh,&nbsp;Xuemo Fan,&nbsp;Jeremy Rudnick,&nbsp;Eric Vail","doi":"10.2217/cns-2019-0019","DOIUrl":"https://doi.org/10.2217/cns-2019-0019","url":null,"abstract":"<p><p>Endolymphatic sac tumors (ELSTs) are rare, locally invasive, vascular tumors of the temporal bone. These lesions are associated with von Hippel-Lindau syndrome but may arise sporadically. Early surgical intervention is recommended to prevent permanent neurologic deficits; however, many ELSTs are unresectable or are subtotally resected due to neurovascular compromise. Chemotherapeutic salvage therapy in trials of neoplasms of associated syndromes has targeted angiogenesis with variable response. We present the case of a sporadic ELST, previously minimally responsive to bevacizumab, treated with pazopanib, a multi-kinase inhibitor and antiangiogenic, with good response. Cases such as our patient may demonstrate the utility of novel antiangiogenics in the treatment of these rare neoplasms, particularly when the tumor is unresectable or necessitates subtotal resection.</p>","PeriodicalId":10469,"journal":{"name":"CNS Oncology","volume":"9 1","pages":"CNS50"},"PeriodicalIF":0.0,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/cns-2019-0019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37711274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges of targeting <i>BRAF</i> V600E mutations in adult primary brain tumor patients: a report of two cases.","authors":"Matthew Smith-Cohn,&nbsp;Christian Davidson,&nbsp;Howard Colman,&nbsp;Adam L Cohen","doi":"10.2217/cns-2019-0018","DOIUrl":"https://doi.org/10.2217/cns-2019-0018","url":null,"abstract":"<p><p><b>Aim:</b> Therapeutic targeting of <i>BRAF</i> alterations in primary brain tumor patients has demonstrated clinical activity in case reports and early trials; however, there is limited high-level evidence of the efficacy. <b>Patients & results:</b> Targeting <i>BRAF</i> V600E mutations with concurrent dabrafenib and trametinib in anaplastic pleomorphic xanthoastrocytoma resulted in a transient radiographic and clinical response and no therapeutic benefit in a patient with an epithelioid glioblastoma. <b>Conclusion:</b><i>BRAF</i>/<i>MEK</i> inhibition did not produce a durable treatment effect in glioblastoma or pleomorphic xanthoastrocytoma with <i>BRAF V600E</i> alterations. Heterogenicity of related cases in the literature makes an evaluation of efficacy <i>BRAF</i> targeting therapies in gliomas difficult and requires additional investigation.</p>","PeriodicalId":10469,"journal":{"name":"CNS Oncology","volume":"8 4","pages":"CNS48"},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/cns-2019-0018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49675093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}