A5009693000- Neuroblastoma Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Cancer therapeutics and mechanisms
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Glioma Diagnosis and Treatment
- Lung Cancer Research Studies
- Cancer Genomics and Diagnostics
- Polyamine Metabolism and Applications
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Cancer Research and Treatments
- Cell death mechanisms and regulation
- Monoclonal and Polyclonal Antibodies Research
- RNA modifications and cancer
- Chromatin Remodeling and Cancer
- Sarcoma Diagnosis and Treatment
- CAR-T cell therapy research
- Virus-based gene therapy research
- Histone Deacetylase Inhibitors Research
- Pancreatic function and diabetes
- interferon and immune responses
- Epigenetics and DNA Methylation
- Angiogenesis and VEGF in Cancer
- Bioactive Compounds and Antitumor Agents
Children's Hospital of Philadelphia
2025
Pennsylvania State University
2025
Levine Children's Hospital
2021-2024
Penn State Milton S. Hershey Medical Center
2023-2024
Levine Cancer Institute
2022
Helen DeVos Children's Hospital
2011-2021
Michigan State University
2012-2021
Corewell Health Blodgett Hospital
2017-2020
Spectrum Health
2017-2020
Grand Rapids Community College
2012-2020
Neuroblastoma (NB) is the most common cancer in infancy and frequent cause of death from extracranial solid tumors children. Ornithine decarboxylase (ODC) expression an independent indicator poor prognosis NB patients. This study investigated safety, response, pharmacokinetics, genetic metabolic factors associated with ODC a clinical trial inhibitor difluoromethylornithine (DFMO) ± etoposide for patients relapsed or refractory NB.
Abstract High risk neuroblastoma (HRNB) accounts for 15% of all pediatric cancer deaths. Despite aggressive therapy approximately half patients will relapse, typically with only transient responses to second-line therapy. This study evaluated the ornithine decarboxylase inhibitor difluoromethylornithine (DFMO) as maintenance prevent relapse following completion standard (Stratum 1) or after salvage relapsed/refractory disease 2). Phase II single agent, arm multicenter enrolled from June 2012...
Long-term survival in high-risk neuroblastoma (HRNB) is approximately 50%, with mortality primarily driven by relapse. Eflornithine (DFMO) to reduce risk of relapse after completion immunotherapy was investigated previously a single-arm, phase II study (NMTRC003B; ClinicalTrials.gov identifier: NCT02395666) that suggested improved event-free (EFS) and overall (OS) compared historical rates III trial (Children Oncology Group ANBL0032; NCT00026312). Using patient-level data from ANBL0032 as an...
Neuroblastoma (NB) is associated with MYCN oncogene amplification occurring in approximately 30% of NBs and poor prognosis. linked to a number genes including ornithine decarboxylase (ODC), the rate-limiting enzyme polyamine biosynthesis. ODC expression elevated many forms cancer NB. Alpha-difluoromethylornithine (DFMO), an inhibitor, currently being used Phase I clinical trial for treatment However, cells treated DFMO may overcome their depletion by uptake polyamines from extracellular...
Most high-risk neuroblastoma patients who relapse succumb to disease despite the existing therapy. We recently reported increased event-free and overall survival in receiving difluoromethylornithine (DFMO) during maintenance The effect of DFMO on cellular processes associated with tumorigenesis needs further elucidation. Previous studies have shown cytotoxicity IC50 values >5-15 mM, these doses are physiologically unattainable patients, prompting mechanistic at therapeutic doses.
// Ann M. Lozier 1 , Maria E. Rich Anissa Pedersen Grawe Anderson S. Peck 2 Ping Zhao Anthony Ting-Tung Chang Jeffrey P. Bond 3 and Giselle Saulnier Sholler 1,4 Pediatric Oncology Translational Research Program, Helen DeVos Children’s Hospital, Grand Rapids, MI, USA Small Animal Imaging Facility, Van Andel Institute, University of Vermont, Michigan State University, 4 College Human Medicine, Correspondence: Sholler, email: Keywords : neuroblastoma, DFMO, LIN28B, glycolytic metabolism,...
Neuroblastoma is a sympathetic nervous system tumor, primarily presenting in children under 6 years of age. The long-term prognosis for patients with high-risk neuroblastoma (HRNB) remains poor despite aggressive multimodal therapy. This report provides an update to phase II trial evaluating DFMO as maintenance therapy HRNB. Event-free survival (EFS) and overall (OS) 81 subjects HRNB treated standard COG induction, consolidation immunotherapy followed by 2 on the NMTRC003/003b Phase were...
Children with relapsed central nervous system (CNS tumors), neuroblastoma, sarcomas, and other rare solid tumors face poor outcomes. This prospective clinical trial examined the feasibility of combining genomic transcriptomic profiling tumor samples a molecular board (MTB) approach to make real‑time treatment decisions for children relapsed/refractory tumors. Subjects were divided into three strata: stratum 1-relapsed/refractory neuroblastoma; 2-relapsed/refractory CNS tumors;...
Abstract Purpose: DROSHA, DGCR8, and DICER1 regulate microRNA biogenesis are commonly mutated in cancer. Whereas DGCR8 germline pathogenic variants (GPVs) cause autosomal dominant tumor predisposition, no association between DROSHA GPVs clinical phenotypes has been reported. Experimental Design: After obtaining informed consent, sequencing was performed on samples from all patients. The occurrence of investigated large pediatric adult cancer datasets. population prevalence the UK Biobank...
The primary aim of this phase 1 study was to determine the maximum tolerated dose (MTD) and evaluate safety nifurtimox alone in combination with cyclophosphamide topotecan multiple relapsed/refractory neuroblastoma pediatric patients. secondary pharmacokinetics treatment response. To these ends, we performed a escalation trial daily oral toxicity monitoring MTD, followed by 3 cycles topotecan. Samples were collected pharmacokinetic parameters concentration, time at which concentration is...
Neuroblastoma (NB) is a deadly childhood disease that carries 50% chance of relapse for anyone in remission and similar level 5-year survival. We investigated the value our proprietary approach—cell surface vimentin (CSV) positive circulating tumor cells (CTC) to monitor treatment response predict NB patients under Phase II long-term preventative clinical trial. longitudinally analyzed peripheral blood samples from 93 27 cycles (~25 months) discovered presence CSV+ CTCs first two sequential...
Abstract Aim In this publication, we will share our experience of AE management, provide guidance for appropriate staffing, and the discuss importance patient education when treating patients with R/R HR neuroblastoma using naxitamab. Background Approved treatments refractory and/or relapsed (R/R) high‐risk (HR) are limited, there is a high unmet need new treatment combinations. Naxitamab disialoganglioside 2 (GD2)‐binding antibody that was approved by United States Food Drug Administration...
Neuroblastoma is the most common extracranial solid tumor in children and, when disseminated, carries a poor prognosis. Even with aggressive combinations of chemotherapy, surgery, autologous bone marrow transplant, and radiation, long-term survival remains at 30% new therapies are needed. Recently, patient neuroblastoma who acquired Chagas disease was treated nifurtimox subsequent reduction size. The effect on cell lines CHLA-90, LA1-55n, LA-N2, SMS-KCNR, SY5Y examined. Nifurtimox decreased...
Abstract Background The combination of vinblastine and mammalian target rapamycin (mTOR) inhibitor sirolimus inhibits the growth neuroblastoma xenografts through pro‐apoptotic anti‐angiogenic mechanisms. This phase I study aimed to explore safety toxicity this in pediatric patients with advanced solid tumors. Procedure Patients ≤21 years age recurrent/refractory tumors (including CNS) were eligible. Sirolimus was administered daily by mouth or nasogastric (NG) tube, doses adjusted achieve a...
Abstract Current therapeutic options for recurrent neuroblastoma have poor outcomes that warrant the development of novel strategies. Specificity protein (Sp) transcription factors regulate several genes involved in cell proliferation, survival, and angiogenesis. Sp1 regulates believed to be important determinants biological behavior neuroblastoma. Tolfenamic acid (TA), a non‐steroidal anti‐inflammatory drug, is known induce degradation Sp proteins may serve as anti‐cancer agent. The...
Abstract The primary objective of the study was to evaluate feasibility and safety a process which would utilize genome‐wide expression data from tumor biopsies support individualized treatment decisions. Current options for recurrent neuroblastoma are limited ineffective, with survival rate <10%. Molecular profiling may provide will enable practitioner select most appropriate therapeutic option individual patients, thus improving outcomes. Sixteen patients were enrolled fourteen eligible...
Background The primary aim of this Phase I study was to determine the maximum tolerated dose (MTD) TPI 287 and safety tolerability alone in combination with temozolomide (TMZ) pediatric patients refractory or recurrent neuroblastoma medulloblastoma. secondary aims were evaluate pharmacokinetics treatment responses. Procedure Eighteen enrolled a phase escalation trial weekly intravenous infusion for two 28‐day cycles toxicity monitoring MTD, followed by TMZ. Samples collected pharmacokinetic...
Background Chemotherapy-resistant neuroblastoma is a difficult disease to treat with poor survival. Observations We treated patient who had progressed on conventional chemotherapy. This 5-year-old girl chemotherapy-resistant developed Chagas at the start of salvage chemotherapy for which she was also started nifurtimox. The response these treatments resulted in clinical remission. In vitro, treatment cell line nifurtimox decreased viability whereas no effect seen an endothelial line....
In this study, we investigated the cytotoxic effects of a broad-spectrumhistone deacetylase(HDAC) inhibitor, PCI-24781, alone and in combination with proteasome inhibitor bortezomib neuroblastoma cell lines.The was shown to induce synergistic cytotoxity involving formation reactive oxygen species.The cleavage caspase-3 PARP, as determined by western blotting, indicated that death primarily due apoptosis.Xenograft mouse models indicatedincreased survival among animalstreated combination.The...
A formal Mentorship Program within the Children’s Oncology Group (COG) was established to pair young investigators (mentees) with COG members (mentors). Despite American Academy of Pediatrics policy statement promoting mentorship programs, there are no publications describing and evaluating national programs in pediatric subspecialties. In this study, a series internal program evaluations were performed using surveys both mentors mentees. Responses deidentified analyzed determine utility by...
Abstract Children with treatment-refractory or relapsed (R/R) tumors face poor prognoses. As the genomic underpinnings driving R/R disease are not well defined, we describe here and transcriptomic landscapes of solid from 202 patients enrolled in Beat Childhood Cancer Consortium clinical trials. Tumor mutational burden (TMB) was elevated relative to untreated at diagnosis, one-third classified as having a pediatric high TMB. Prior chemotherapy exposure influenced landscape these tumors, more...
Abstract Purpose: Placental growth factor (PlGF) and its receptor neuropilin 1 are elevated in malignant embryonal tumors mediate tumor progression by promoting cell proliferation, survival, metastasis. TB-403 is a blocking monoclonal antibody against PlGF that inhibits increases survival orthotopic medulloblastoma models. Patients Methods: We conducted phase I, open-label, multicenter, dose-escalation study of pediatric subjects with relapsed or refractory cancers. The involved four dose...
Abstract Background Nerve growth factor and neurotrophin-3 are involved in the development of sympathetic neurons; however, whether brain derived neurotrophic also plays a role is not known. The purpose this study was to determine BDNF its receptor, TrkB, expressed during paravertebral ganglia vivo effect vitro . Results As neural crest cells coalesce form ganglia, TrkB-positive seen both chicken mouse embryos. In embryos, TrkB-expressing first appear at Hamburger-Hamilton Stage (St) 27 they...