Publications by authors named "E Antonio Chiocca"

446 Publications

Neurosurgery Research and Education Foundation funding conversion to National Institutes of Health funding.

J Neurosurg 2021 Jun 11:1-8. Epub 2021 Jun 11.

1Department of Neurological Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio.

Objective: The Neurosurgery Research and Education Foundation (NREF) provides research support for in-training and early career neurosurgeon-scientists. To define the impact of this funding, the authors assessed the success of NREF awardees in obtaining subsequent National Institutes of Health (NIH) funding.

Methods: NREF in-training (Research Fellowship [RF] for residents) and early career awards/awardees (Van Wagenen Fellowship [VW] and Young Clinician Investigator [YCI] award for neurosurgery faculty) were analyzed. NIH funding was defined by individual awardees using the NIH Research Portfolio Online Reporting tool (1985-2014).

Results: Between 1985 and 2014, 207 unique awardees were supported by 218 NREF awards ($9.84 million [M] in funding), including 117 RF ($6.02 M), 32 VW ($1.68 M), and 69 YCI ($2.65 M) awards. Subspecialty funding included neuro-oncology (79 awards; 36% of RF, VW, and YCI awards), functional (53 awards; 24%), vascular (37 awards; 17%), spine (22 awards; 10%), pediatrics (18 awards; 8%), trauma/critical care (5 awards; 2%), and peripheral nerve (4 awards; 2%). These awardees went on to receive $353.90 M in NIH funding that resulted in an overall NREF/NIH funding ratio of 36.0:1 (in dollars). YCI awardees most frequently obtained later NIH funding (65%; $287.27 M), followed by VW (56%; $41.10 M) and RF (31%; $106.59 M) awardees. YCI awardees had the highest NREF/NIH funding ratio (108.6:1), followed by VW (24.4:1) and RF (17.7:1) awardees. Subspecialty awardees who went on to obtain NIH funding included vascular (19 awardees; 51% of vascular NREF awards), neuro-oncology (40 awardees; 51%), pediatrics (9 awardees; 50%), functional (25 awardees; 47%), peripheral nerve (1 awardees; 25%), trauma/critical care (2 awardees; 20%), and spine (2 awardees; 9%) awardees. Subspecialty NREF/NIH funding ratios were 56.2:1 for vascular, 53.0:1 for neuro-oncology, 47.6:1 for pediatrics, 34.1:1 for functional, 22.2:1 for trauma/critical care, 9.5:1 for peripheral nerve, and 0.4:1 for spine. Individuals with 2 NREF awards achieved a higher NREF/NIH funding ratio (83.3:1) compared to those with 1 award (29.1:1).

Conclusions: In-training and early career NREF grant awardees are an excellent investment, as a significant portion of these awardees go on to obtain NIH funding. Moreover, there is a potent multiplicative impact of NREF funding converted to NIH funding that is related to award type and subspecialty.
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http://dx.doi.org/10.3171/2020.11.JNS203871DOI Listing
June 2021

Activity of PD-1 blockade with Nivolumab among patients with recurrent atypical/anaplastic meningioma: Phase II trial results.

Neuro Oncol 2021 May 20. Epub 2021 May 20.

Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Background: Programmed death-1 ligand (PD-L1) contributes to tumor immunosuppression and is upregulated in aggressive meningiomas. We performed a phase II study of nivolumab, a programmed death-1 (PD-1) blocking antibody among patients with grade ≥2 meningioma that recurred after surgery and radiation therapy.

Methods: Twenty-five patients received nivolumab (240 mg biweekly) until progression, voluntary withdrawal, unacceptable toxicity, or death. Tumor mutational burden (TMB) and quantification of tumor infiltrating lymphocytes (TIL) were evaluated as potential immunocorrelative biomarkers. Change in neurologic function was prospectively assessed using the Neurologic Assessment in Neuro-Oncology (NANO) scale.

Results: Enrolled patients had multiple recurrences including ≥3 prior surgeries and ≥2 prior courses of radiation in 60% and 72%, respectively. Nivolumab was well tolerated with no unexpected AEs. PFS-6 was 42.4% (95% CI: 22.8, 60.7) and the median OS was 30.9 months (95% CI: 17.6, NA). One patient achieved radiographic response (ongoing at 4.5 years). TMB was > 10/Mb in 2 of 15 profiled tumors (13.3%). Baseline TIL density was low but increased post-treatment in 3 patients including both patients with elevated TMB. Most patients who achieved PFS-6 maintained neurologic function prior to progression as assessed by NANO.

Conclusion: Nivolumab was well tolerated but failed to improve PFS-6, although a subset of patients appeared to derive benefit. Low levels of TMB and TIL density were typically observed. NANO assessment of neurologic function contributed to outcome assessment. Future studies may consider rationally designed combinatorial regimens.
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http://dx.doi.org/10.1093/neuonc/noab118DOI Listing
May 2021

Association of Immune Thrombocytopenia and Coeliac Disease in Children (Retrospective Case Control Study).

Turk J Haematol 2021 May 18. Epub 2021 May 18.

U.O.C. Oncoematologia Pediatrica - ARNAS Civico - Di Cristina - Benfratelli, Palermo.

Objective: The association between coeliac disease (CD) and immune thrombocytopenia (ITP) is still uncertain. The aim of this study was to characterize the coexistence of these two diseases in Italian children.

Materials And Methods: This is a multicenter retrospective study investigating the occurrence of CD in 28 children with ITP diagnosed from January 1th 2000 to December 31th 2019.

Results: The first diagnosis was ITP in 57.1% and CD in 32.1% of patients. In 3 patients (10.7%) the two diagnosis were simultaneous. All the potential and silent CDs in our cohort were diagnosed in the groups of and . In all children ITP was mild and in 2 out of 8 not recovered from ITP at the time of CD diagnosis a normalization of platelet counts (> 100,000/mmc) occurred after 3 and 5 months from starting gluten free diet.

Discussion: We think that screening for celiac disease should be considered in children with ITP, regardless the presence of gastrointestinal symptoms. Furthermore some patients could recover from ITP after starting gluten-free diet.
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http://dx.doi.org/10.4274/tjh.galenos.2021.2021.0128DOI Listing
May 2021

Targeting glioblastoma using a novel peptide specific to a deglycosylated isoform of brevican.

Adv Ther (Weinh) 2021 Apr 20;4(4). Epub 2021 Jan 20.

Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States.

Glioblastoma multiforme (GBM) is the most common and deadliest form of brain tumor and remains amongst the most difficult cancers to treat. Brevican (Bcan), a central nervous system (CNS)-specific extracellular matrix protein, is upregulated in high-grade glioma cells, including GBM. A Bcan isoform lacking most glycosylation, dg-Bcan, is found only in GBM tissues. Here, dg-Bcan is explored as a molecular target for GBM. In this study, we screened a d-peptide library to identify a small 8-amino acid dg-can-argeting eptide (BTP) candidate, called BTP-7 that binds dg-Bcan with high affinity and specificity. BTP-7 is preferentially internalized by dg-Bcan-expressing patient-derived GBM cells. To demonstrate GBM targeting, we radiolabeled BTP-7 with F, a radioisotope of fluorine, and found increased radiotracer accumulation in intracranial GBM established in mice using positron emission tomography (PET) imaging. dg-Bcan is an attractive molecular target for GBM, and BTP-7 represents a promising lead candidate for further development into novel imaging agents and targeted therapeutics.
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http://dx.doi.org/10.1002/adtp.202000244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114962PMC
April 2021

Cytomegalovirus infection of glioblastoma cells leads to NF-κB dependent upregulation of the c-MET oncogenic tyrosine kinase.

Cancer Lett 2021 Aug 12;513:26-35. Epub 2021 May 12.

Harvey Cushing Neurooncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:

Cytomegalovirus (CMV) is widespread in humans and has been implicated in glioblastoma (GBM) and other tumors. However, the role of CMV in GBM remains poorly understood and the mechanisms involved are not well-defined. The goal of this study was to identify candidate pathways relevant to GBM that may be modulated by CMV. Analysis of RNAseq data after CMV infection of patient-derived GBM cells showed significant upregulation of GBM-associated transcripts including the MET oncogene, which is known to play a role in a subset of GBM patients. These findings were validated in vitro in both mouse and human GBM cells. Using immunostaining and RT-PCR in vivo, we confirmed c-MET upregulation in a mouse model of CMV-driven GBM progression and in human GBM. siRNA knockdown showed that MET upregulation was dependent on CMV-induced upregulation of NF-κB signaling. Finally, proneural GBM xenografts overexpressing c-MET grew much faster in vivo than controls, suggesting a mechanism by which CMV infection of tumor cells could induce a more aggressive mesenchymal phenotype. These studies implicate the CMV-induced upregulation of c-MET as a potential mechanism involved in the effects of CMV on GBM growth.
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http://dx.doi.org/10.1016/j.canlet.2021.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209659PMC
August 2021