A5065887488- Sarcoma Diagnosis and Treatment
- Ovarian cancer diagnosis and treatment
- Tumors and Oncological Cases
- Chromatin Remodeling and Cancer
- Neuroblastoma Research and Treatments
- Soft tissue tumor case studies
- Hippo pathway signaling and YAP/TAZ
- Renal and related cancers
- Cancer Mechanisms and Therapy
- Childhood Cancer Survivors' Quality of Life
- Bone Tumor Diagnosis and Treatments
- Cancer therapeutics and mechanisms
- CAR-T cell therapy research
- Lymphoma Diagnosis and Treatment
- Peptidase Inhibition and Analysis
- Protein Degradation and Inhibitors
- Immune Cell Function and Interaction
- RNA Research and Splicing
- Neuroendocrine Tumor Research Advances
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Neurofibromatosis and Schwannoma Cases
- Vascular Tumors and Angiosarcomas
- Cancer-related gene regulation
- Hedgehog Signaling Pathway Studies
Cincinnati Children's Hospital Medical Center
2016-2025
University of Cincinnati Medical Center
2019-2025
University of Cincinnati
2016-2025
University of Alabama at Birmingham
2009-2023
Cook Children's Medical Center
2023
Nationwide Children's Hospital
2022-2023
Columbus Center
2023
Children's of Alabama
2007-2019
University of Alabama
2019
Foundation Medicine (United States)
2017
Desmoid tumors are rare, locally aggressive, highly recurrent soft-tissue without approved treatments. Download a PDF of the Research Summary. We conducted phase 3, international, double-blind, randomized, placebo-controlled trial nirogacestat in adults with progressing desmoid according to Response Evaluation Criteria Solid Tumors, version 1.1. Patients were assigned 1:1 ratio receive oral γ-secretase inhibitor (150 mg) or placebo twice daily. The primary end point was progression-free...
Cytokine release syndrome (CRS) is a phenomenon of immune hyperactivation described in the setting cellular and bispecific T-cell engaging immunotherapy. Checkpoint blockade using anti-programmed cell death 1 (anti-PD-1) inhibitors an approach to antitumor system stimulation. A 29-year-old female with alveolar soft part sarcoma developed severe CRS after treatment anti-PD-1 therapy. was characterized by high fevers, encephalopathy, hypotension, hypoxia, hepatic dysfunction, evidence...
Rhabdomyosarcoma (RMS) typically arises from skeletal muscle. Currently, RMS in patients with recurrent and metastatic disease have no successful treatment. The molecular pathogenesis of varies based on cancer sub-types. Some embryonal but not other sub-types are driven by sonic hedgehog (Shh) signaling pathway. However, Shh pathway inhibitors particularly smoothened highly effective animals. Here, we show that effectors GLI1 and/or GLI2 over-expressed the majority cells GANT-61, a specific...
Many patients with histiocytic disorders such as Langerhans cell histiocytosis (LCH) or Erdheim-Chester disease (ECD) have treatment-refractory suffer recurrences. Recent findings of gene mutations in histiocytoses generated options for targeted therapies. We sought to determine the utility prospective sequencing select genes further characterize and identify therapies histiocytoses. Biopsies 72 a variety underwent comprehensive genomic profiling DNA RNA sequencing. Fifteen (21%) carried...
In neurofibromatosis type 1 (NF1) and in highly aggressive malignant peripheral nerve sheath tumors (MPNSTs), constitutively active RAS-GTP increased MAPK signaling are important tumorigenesis. Dual specificity phosphatases (DUSPs) negative regulators of that dephosphorylate p38, JNK, ERK different settings. Although often acting as tumor suppressors, DUSPs may also act oncogenes, helping cells adapt to high levels signaling. We hypothesized inhibiting might be selectively toxic from...
Introduction: CD3+ γδ+ T cells comprise 2% to 5% of circulating with Vγ9Vδ2+ the dominant subtype. recognize non-peptide phosphoantigens and stress-associated NKG2D ligands expressed on malignant cells. Strategies that incorporate tumoricidal properties γδ represent a promising immunotherapeutic strategy for treatment solid malignancies including neuroblastoma (NB). In this prospective, non-randomized Phase I trial, we assessed whether could be safely expanded using intravenous ZOL...
There are no known effective medical treatments for refractory MPNST. Inactivation of the NF1 tumor suppressor in MPNST results upregulation mTOR (mammalian target rapamycin) signaling and angiogenesis, which contributes to disease progression. We conducted a phase II study patients (pts) with combining everolimus (10 mg PO once daily) bevacizumab mg/kg IV every 2 weeks) determine clinical benefit rate (CBR) (complete response, partial response (PR), or stable (SD) ≥ 4 months).Patients ≥18...
The self-reactive T cells that escape clonal deletion in the thymus must be suppressed by less well characterized process of peripheral tolerance. In this study, we show monocyte-derived macrophages (M phi) undergoing terminal differentiation presence macrophage CSF (M-CSF) acquire ability to selectively induce apoptosis an activation-specific fashion. Lymphocytes were stimulated via TCR using anti-CD3 cross-linking, staphylococcal superantigen, or allogeneic mixed-leukocyte cultures....
Abstract Background Aberrant activation of the hedgehog (Hh) signaling pathway is implicated widely in both pediatric and adult malignancies. Inactivation Hh regulator PTCH responsible for Gorlin cancer predisposition syndrome. The spectrum tumors found Syndrome includes basal cell carcinoma, medulloblastoma, rarely, rhabdomyosarcoma (RMS). A previous report utilizing situ hybridization has provided initial evidence expression targets GLI1 RMS tumors. Procedure To investigate role...
BACKGROUND Lymph node metastases are an important cause of treatment failure for pediatric and adolescent/young adult (AYA) sarcoma patients. Nodal sampling is recommended certain subtypes that have a predilection lymphatic spread. Sentinel lymph biopsy (SLNB) may improve the diagnostic yield nodal sampling, particularly when single‐photon emission computed tomography/computed tomography (SPECT‐CT) used to facilitate anatomic localization. Functional imaging with positron (PET‐CT)...
Gorham-Stout disease is a life-threatening disorder often manifested by lymphatic malformation and osteolysis. Unfortunately, available therapies are not uniformly effective carry substantial morbidity. We report an 18-year-old male with lytic rib lesions intractable pleural effusion that responded dramatically to the combination of mammalian target rapamycin (mTOR) inhibitor sirolimus aminobisphosphonate zoledronic acid after failing interferon therapy. This tolerable therapeutic has...
Importance Although most ovarian masses in children and adolescents are benign, many managed with oophorectomy, which may be unnecessary can have lifelong negative effects on health. Objective To evaluate the ability of a consensus-based preoperative risk stratification algorithm to discriminate between benign malignant pathology decrease oophorectomies. Design, Setting, Participants Pre/post interventional study patients aged 6 21 years undergoing surgery for an mass inpatient setting 11...
Abstract Rhabdomyosarcoma (RMS) is a common soft-tissue sarcoma of childhood in need more effective therapeutic options. The expression p53 RMS heterogeneous such that some tumors are wild-type whereas others mutant. small molecule CP-31398 modulates both the and mutant proteins. Here, we show blocks growth cells have either or status. In A204 cells, increased its downstream transcriptional targets, p21 mdm2; enhanced apoptosis-related proteins; reduced proliferation biomarkers. Flow...
Infantile hemangiomas (IHs) are common benign tumors of childhood. IHs often regress satisfactorily without intervention, but a subset may lead to functional or cosmetic morbidity necessitating therapy. PHACE syndrome is characterized by variety neurocutaneous and vascular anomalies that typically include segmental hemangiomas. We present an infant with IH failed conventional first-line therapies. Treatment sirolimus provided benefit regression the cutaneous IH. As inhibitor mammalian target...
CIC- rearranged sarcomas rarely occur in visceral organs including the kidney. The most common fusion partner with CIC is DUX4 gene, but variant partners have also been reported. Herein, we describe clinicopathologic features and comprehensive molecular profiling of 4 cases primary renal sarcomas. All occurred females, age range 13 to 82 years included 3 resections 1 needle biopsy specimen. There was a tendency for development metastatic disease predominantly lungs poor outcome despite...
Background Lorvotuzumab mertansine (IMGN901) is an antibody‐drug conjugate linking antimitotic agent (DM1) to anti‐CD56 antibody (lorvotuzumab). Preclinical efficacy has been noted in Wilms tumor, rhabdomyosarcoma, and neuroblastoma. Synovial sarcoma, malignant peripheral nerve sheath tumor (MPNST), pleuropulmonary blastoma also express CD56. A phase 2 trial of lorvotuzumab was conducted assess its efficacy, recommended dose, toxicities. Methods Eligible patients had relapsed after or...
Introduction: Adolescent/young adult (AYA) patients with metastatic soft tissue sarcoma (STS) typically face a dismal prognosis. However, subset of incurable disease lives beyond two years. Due to the rarity diagnoses and inherent heterogeneity within this population, paucity data exists regarding experiences AYAs an indolent course (and how best capture these experiences). With increasing biological insight clinical experience, including use targeted or immune therapies, it is anticipated...