Publications by authors named "Xiaobu Ye"

H3K27M-mutant diffuse midline gliomas (DMGs) express high levels of the disialoganglioside GD2 (ref. ). Chimeric antigen receptor-modified T cells targeting GD2 (GD2-CART) eradicated DMGs in preclinical models.

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  • Oligodendroglioma is a brain tumor characterized by specific genetic mutations and treatments typically involve surgery followed by either observational care or a combination of radiation and chemotherapy.
  • This study analyzed data from 277 patients with IDH-mutant, 1p/19q codeleted oligodendrogliomas to examine the impact of different adjuvant treatment regimens on progression-free survival (PFS).
  • Results indicated that patients with grade 3 tumors showed significantly longer PFS when treated with radiation and PCV chemotherapy compared to those receiving radiation with TMZ or no adjuvant therapy, emphasizing the need for more research in this area.
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  • Lisavanbulin (BAL101553) is an oral drug designed to destabilize microtubules and shows potential against glioblastoma in preclinical studies.
  • A phase 1 study was conducted to determine the maximum tolerated dose (MTD) of Lisavanbulin when given with conventional radiotherapy (RT) in patients with a specific type of glioblastoma, focusing on toxicity and effectiveness.
  • Out of 26 patients, the study found that Lisavanbulin could be safely administered at doses up to 15 mg daily, though some side effects like confusion were noted at 12 mg.
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Unlabelled: We investigated the effectiveness of navtemadlin (KRT-232) in treating recurrent glioblastoma. A surgical window-of-opportunity trial ( NCT03107780 ) was conducted on 21 patients to determine achievable drug concentrations within tumor tissue and examine mechanisms of response and resistance. Both 120 mg and 240 mg daily dosing achieved a pharmacodynamic impact.

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  • Oligodendrogliomas, known for specific genetic mutations (IDH1/2) and chromosome deletions (1p/19q), were analyzed in a study to understand the clinical significance of additional genomic alterations like CIC, FUBP1, and TERTp using clinically standardized NGS panels.
  • The analysis included 277 patients diagnosed between 2005 and 2021, revealing that among the 95 patients with NGS reports, CIC, FUBP1, and TERTp were the most commonly altered genes.
  • While these genetic alterations were frequent, the study found that most did not significantly impact progression-free or overall survival, except for a noted reduction in progression-free survival associated with CIC alterations in specific
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Background: When arsenic trioxide (ATO) was combined with radiation for treatment of transplanted murine gliomas in the brain, tumor response improved with disrupted tumor blood flow and survival was significantly prolonged.

Methods: Total of 31 patients with newly diagnosed glioblastoma were accrued to a multi-institutional, NCI-funded, phase I study to determine the maximum tolerated dose (MTD) of ATO administered with radiation. Secondary objectives were survival and pharmacodynamic changes in perfusion on magnetic resonance imaging (MRI).

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H3K27M-mutant diffuse midline gliomas (DMGs) express high levels of the GD2 disialoganglioside and chimeric antigen receptor modified T-cells targeting GD2 (GD2-CART) eradicate DMGs in preclinical models. Arm A of the Phase I trial NCT04196413 administered one IV dose of autologous GD2-CART to patients with H3K27M-mutant pontine (DIPG) or spinal (sDMG) diffuse midline glioma at two dose levels (DL1=1e6/kg; DL2=3e6/kg) following lymphodepleting (LD) chemotherapy. Patients with clinical or imaging benefit were eligible for subsequent intracerebroventricular (ICV) GD2-CART infusions (10-30e6 GD2-CART).

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Recurrent high-grade gliomas (rHGGs) have a dismal prognosis, where the maximum tolerated dose (MTD) of IV terameprocol (5 days/month), a transcriptional inhibitor of specificity protein 1 (Sp1)-regulated proteins, is 1,700 mg/day with median area under the plasma concentration-time curve (AUC) of 31.3 μg∗h/mL. Given potentially increased efficacy with sustained systemic exposure and challenging logistics of daily IV therapy, here we investigate oral terameprocol for rHGGs in a multicenter, phase 1 trial (GATOR).

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Purpose: Patients with glioblastoma (GBM) have a dismal prognosis. Although the DNA alkylating agent temozolomide (TMZ) is the mainstay of chemotherapy, therapeutic resistance rapidly develops in patients. Base excision repair inhibitor TRC102 (methoxyamine) reverses TMZ resistance in preclinical glioma models.

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Background: Postoperative stroke is a potentially devastating neurological complication following surgical revascularization for Moyamoya disease. We sought to evaluate whether peri-operative hemoglobin levels were associated with the risk of early post-operative stroke following revascularization surgery in adult Moyamoya patients.

Methods: Adult patients having revascularization surgeries for Moyamoya disease between 1999-2022 were identified through single institutional retrospective review.

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Adult medulloblastomas (MB) are rare, and optimal post-craniospinal irradiation (CSI) chemotherapy is not yet defined. We investigated hematological toxicity in patients treated with platinum-etoposide (EP) post-CSI. Retrospective, single-institution study to determine hematological toxicity in adult MB patients treated with EP (1995-2022).

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Purpose: Although fewer than 5% of high-grade gliomas (HGG) are BRAF-V600E mutated, these tumors are notable as BRAF-targeted therapy shows efficacy for some populations. The purpose of this study was to evaluate response to the combination of encorafenib with binimetinib in adults with recurrent BRAF-V600-mutated HGG.

Patients And Methods: In this phase 2, open-label, Adult Brain Tumor Consortium (ABTC) trial (NCT03973918), encorafenib and binimetinib were administered at their FDA-approved doses continuously in 28-day cycles.

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Purpose: AT-101 is an oral bcl-2 family protein inhibitor (Bcl-2, Bcl-XL, Mcl-1, Bcl-W) and potent inducer of proapoptotic proteins. A prior study of the parent compound, racemic gossypol, demonstrated objective and durable responses in patients with malignant glioma. AT-101 has demonstrated synergy with radiation in animal models.

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Objective: Careful hematologic management is required in surgical patients with traumatic acute subdural hematoma (aSDH) taking antithrombotic medications. We sought to compare outcomes between patients with aSDH taking antithrombotic medications at admission who received antithrombotic reversal with patients with aSDH not taking antithrombotics.

Methods: Retrospective review identified patients with traumatic aSDH requiring surgical evacuation.

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Purpose: A multi-site Phase I trial was conducted to determine the safety, maximum tolerated dose, and pharmacokinetics (PK) of Veliparib, a Poly (ADP-ribose) polymerase [PARP] enzyme inhibitor, when administered with temozolomide (TMZ) alone and then with temozolomide and radiation (RT) in patients with newly diagnosed glioblastoma.

Methods: Given the potential for myelosuppression when a PARP inhibitor is combined with chemotherapy, the first 6 patients accrued were given Veliparib 10 mg bid and TMZ 75 mg/m2/d daily for six weeks. If this was well tolerated, the same doses of Veliparib and TMZ would be tested along with standard radiation with plans to dose escalate the Veliparib in subsequent patient cohorts.

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Article Synopsis
  • Acute subdural hematoma (aSDH) after traumatic brain injury often requires urgent surgical procedures, specifically craniotomy (CO) or decompressive craniectomy (DC), and the study aimed to compare outcomes and identify variables linked to each approach.
  • The study analyzed data from multiple centers, identifying significant differences in patient characteristics between those undergoing CO and DC, including age, gender, and severity of symptoms at presentation.
  • Findings indicated that patients undergoing DC were generally younger and more likely to have poorer clinical outcomes, with DC being associated with higher mortality rates both during hospitalization and at 90 days and 1 year post-surgery after adjusting for patient differences.
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Purpose: A multi-site Phase I trial was conducted to determine the safety, maximum tolerated dose, and pharmacokinetics (PK) of Veliparib, a Poly (ADP-ribose) polymerase [PARP] enzyme inhibitor, when administered with temozolomide (TMZ) alone and then with temozolomide and radiation (RT) in patients with newly diagnosed glioblastoma.

Methods: Given the potential for myelosuppression when a PARP inhibitor is combined with chemotherapy, the first 6 patients accrued were given Veliparib 10 mg bid and TMZ 75 mg/m2/d daily for six weeks. If this was well tolerated, the same doses of Veliparib and TMZ would be tested along with standard radiation with plans to dose escalate the Veliparib in subsequent patient cohorts.

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Introduction: Hypoxia inducible factor 2-alpha (HIF2α) mediates cellular responses to hypoxia and is over-expressed in glioblastoma (GBM). PT2385 is an oral HIF2α inhibitor with in vivo activity against GBM.

Methods: A two-stage single-arm open-label phase II study of adults with GBM at first recurrence following chemoradiation with measurable disease was conducted through the Adult Brain Tumor Consortium.

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Objective: Brain metastases (BMs) are the most common CNS tumors, yet their prevalence is difficult to determine. Most studies only report synchronous metastases, which make up a fraction of all BMs. The authors report the incidence and prognosis of patients with synchronous and metachronous BMs over a decade.

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Purpose: Gliomagenesis and resistance of glioblastoma (GBM) are believed to be mediated by glioma stem cells (GSC). Evidence suggests that SHH signaling promotes GSC proliferation and self-renewal.

Methods: ABTC-0904 was a two-arm, multicenter phase 0/II study of GDC-0449, an oral inhibitor of Smoothened (SMO) in patients undergoing resection for recurrent GBM.

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Cerebral palsy (CP) is the most common cause of physical disability for children worldwide. Many infants and toddlers are not diagnosed with CP until they fail to achieve obvious motor milestones. Currently, there are no effective pharmacologic interventions available for infants and toddlers to substantially improve their trajectory of neurodevelopment.

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Introduction: Outcomes for patients with high grade gliomas have changed little over the past thirty years. This realization prompted renewed efforts to increase flexibility in the design and conduct of clinical brain tumor trials.

Areas Covered: This manuscript reviews the development of clinical trial methods, challenges and considerations of flexible clinical trial designs, approaches to improve identification and testing of active agents for high grade gliomas, and evaluation of their delivery to the central nervous system.

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Purpose: This proof-of-principle clinical trial evaluated whether an allogeneic multiple myeloma GM-CSF-secreting vaccine (MM-GVAX) in combination with lenalidomide could deepen the clinical response in patients with multiple myeloma in sustained near complete remission (nCR).

Patients And Methods: Fifteen patients on lenalidomide were treated with MM-GVAX and pneumococcal conjugate vaccine (PCV; Prevnar) at 1, 2, 3, and 6 months.

Results: Eight patients (53.

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