A5027520603- Acute Myeloid Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Lymphoma Diagnosis and Treatment
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Acute Lymphoblastic Leukemia research
- Chronic Lymphocytic Leukemia Research
- Cancer-related gene regulation
- Multiple Myeloma Research and Treatments
- Cancer therapeutics and mechanisms
- Retinopathy of Prematurity Studies
- DNA Repair Mechanisms
- Sarcoma Diagnosis and Treatment
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- CAR-T cell therapy research
- HIV/AIDS drug development and treatment
- Neonatal Respiratory Health Research
- Hematopoietic Stem Cell Transplantation
- Cancer Genomics and Diagnostics
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Neuroendocrine regulation and behavior
- Hemoglobinopathies and Related Disorders
- Animal Behavior and Reproduction
The Barbara Ann Karmanos Cancer Institute
2016-2025
Wayne State University
2016-2025
Cornell University
2022-2025
Boston Children's Hospital
2021-2025
Harvard University
2021-2025
City Of Hope National Medical Center
2025
Florida Cancer Specialists & Research Institute
2023
Epizyme (United States)
2019-2022
Michigan United
2021
University of Toronto
2005-2015
Abstract We conducted a phase I clinical trial of H3B-8800, an oral small molecule that binds Splicing Factor 3B1 (SF3B1), in patients with MDS, CMML, or AML. Among 84 enrolled (42 4 CMML and 38 AML), 62 were red blood cell (RBC) transfusion dependent at study entry. Dose escalation cohorts examined two once-daily dosing regimens: schedule (5 days on/9 off, range doses studied 1–40 mg, n = 65) II (21 on/7 7–20 19); 27 received treatment for ≥180 days. The most common treatment-related,...
Olutasidenib (FT-2102) is a potent, selective, oral, small-molecule inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1). Overall, 153 IDH1 inhibitor-naive patients with mIDH1R132 relapsed/refractory (R/R) acute myeloid leukemia (AML) received olutasidenib monotherapy 150 mg twice daily in the pivotal cohort this study. The median age participants was 71 years (range, 32-87 years) and number prior regimens by 2 (1-7). rate complete remission (CR) plus CR partial hematologic recovery (CRh)...
Olutasidenib is a potent, selective, oral, small molecule inhibitor of mutant IDH1 (mIDH1) which induced durable remissions in high-risk, relapsed/refractory (R/R) mIDH1 AML patients phase 1/2 trial. We present pooled analysis from multiple cohorts the trial with R/R who received combination olutasidenib and azacitidine therapy. Adult mIDH1R132 150 mg twice daily plus standard-of-care (OLU + AZA) were evaluated for response safety. Sixty-seven OLU AZA. Median age was 66 years (range 28-82)...
BLM, the helicase mutated in Bloom syndrome, associates with topoisomerase 3α, RMI1 (RecQ-mediated genome instability), and RPA, to form a complex essential for maintenance of stability. Here we report novel component BLM complex, RMI2, which interacts through two oligonucleotide-binding (OB)-fold domains similar those RPA. The resulting named RMI, differs from RPA that it lacks obvious DNA-binding activity. Nevertheless, RMI stimulates dissolution homologous recombination intermediate vitro...
Abstract Background Venetoclax + azacitidine is a frontline treatment for older adult acute myeloid leukemia (AML) patients and salvage therapy relapsed/refractory who have been treated with intensive chemotherapy. While this an important option, many fail to achieve complete remission of those that do, majority relapse. Leukemia stem cells (LSCs) are believed be responsible AML relapse can targeted through oxidative phosphorylation reduction. We previously reported ONC213 disrupts decreases...
11003 Background: ES is a rare soft tissue sarcoma that metastasizes in approximately 30% to 50% of cases. More than 90% tumors lack expression INI1, an important component epigenetic regulation. Loss INI1 function allows another modifier, EZH2, become oncogenic driver tumor cells. Tazemetostat, first-in-class, selective, oral inhibitor has demonstrated regression and favorable safety phase 1/2 trials. Methods: Data from 2 open-label, multicenter trial pts with locally advanced or metastatic...
Induction therapy for patients with acute myeloid leukemia (AML) has remained largely unchanged over 40 years, while overall survival rates remain unacceptably low, highlighting the need new therapies. The PI3K/Akt pathway is constitutively active in majority of AML. Given that histone deacetylase inhibitors have been shown to synergize PI3K preclinical AML models, we investigated novel dual-acting and inhibitor CUDC-907 cells both vitro vivo. We demonstrated induces apoptosis cell lines...
Human topoisomerase IIIα is a type IA DNA that functions with BLM and RMI1 to resolve replication recombination intermediates. BLM, human IIIα, catalyze the dissolution of double Holliday junctions into noncrossover products via strand-passage mechanism. We generated single-stranded catenanes resemble proposed intermediate recognized by IIIα. demonstrate decatenase specifically stimulated BLM-RMI1 pair. In addition, interacts interaction required for stimulatory effect on activity. Our data...
Venetoclax is a promising agent in the treatment of acute myeloid leukemia, though its antileukemic activity limited to combination therapies. Mcl-1 downregulation, Bim upregulation, and DNA damage have been identified as potential ways enhance venetoclax activity. In this study, we combine with dual PI3K histone deacetylase inhibitor CUDC-907, which can downregulate Mcl-1, upregulate Bim, induce damage, well c-Myc. We establish that CUDC-907 synergistically apoptosis leukemia cell lines...
There is a gap in understanding the effect of essential ω-3 and ω-6 long-chain polyunsaturated fatty acids (LCPUFA) on Phase I retinopathy prematurity (ROP), which precipitates proliferative ROP. Postnatal hyperglycemia contributes to ROP by delaying retinal vascularization. In mouse neonates with hyperglycemia-associated retinopathy, dietary (vs. LCPUFA) supplementation promoted vessel development. However, was also developmentally essential, promoting neuronal growth metabolism as...
10040 Background: A defining feature of malignant rhabdoid tumors (MRTs), epithelioid sarcoma (ES), and poorly differentiated chordomas (PDC) is loss integrase interactor 1 (INI1) expression, which induces dependence on enhancer zeste homolog 2 (EZH2). Tazemetostat (TAZ) a selective EZH2 inhibitor approved by the US Food Drug Administration for patients (pts) aged ≥16 y with metastatic or locally advanced ES ineligible complete resection. Pediatric dose escalation interim efficacy safety...
Abstract Purpose. Following the demonstrated efficacy and safety of eribulin mesylate in heavily pretreated patients with metastatic breast cancer, an exploratory analysis was performed to investigate effect age these patients. Methods. Data were pooled from two single-arm phase II studies one open-label randomized III study which received at 1.4 mg/m2 as 2- 5-minute intravenous infusions on days 1 8 a 21-day cycle. The median overall survival (OS), progression-free (PFS), response rate...
Abstract The availability and use of blinatumomab symbolizes a paradigm shift in the management B-cell acute lymphoblastic leukemia (ALL). We conducted retrospective multicenter cohort analysis 239 ALL patients (227 relapsed refractory [RR], n = 227; minimal residual disease [MRD], 12) who received outside clinical trials to evaluate safety efficacy “real-world” setting. median age at initiation was 48 years (range, 18-85). Sixty-one (26%) had ≥3 prior therapies 46 (19%) allogeneic...
Urine marking is central to mouse social behavior. Males use depletable and costly urine marks in intrasexual competition mate attraction. We investigate how males alter signaling decisions across variable landscapes using thermal imaging capture spatiotemporal data. Thermal recording reveals fine-scale adjustments urinary motor patterns response odors. demonstrate striking winner-loser effects scent mark allocation effort timing. Competitive experience primes temporal features of modulates...
The treatment of myeloma has undergone extraordinary improvements in the past half century. These advances have been accompanied by a concern for secondary primary malignancies (SPMs). It known decades that extended therapy with alkylating chemotherapy agents, such as melphalan, carries an increased risk therapy-related myelodysplastic syndrome and/or acute myeloid leukemia (t-MDS/AML), cumulative high 10-15%. High-dose autologous stem cell support became widely accepted 1990s. Despite use...
Entospletinib (GS-9973) is an oral, selective inhibitor of spleen tyrosine kinase. monotherapy was evaluated in a multicenter, phase II study subjects with relapsed or refractory B-cell malignancy.The included 43 patients diffuse large lymphoma (DLBCL). The participants received 800 mg the original, monomesylate formulation entospletinib twice daily as starting dose; doses could be reduced because toxicity throughout study.No patient achieved complete partial response, 5 (12%) had stable...
This study aimed to identify a recommended phase II dose and evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics, preliminary clinical activity of JNJ-63709178, CD123/CD3 dual-targeting antibody, in patients with relapsed or refractory acute myeloid leukemia. Intravenous (i.v.) subcutaneous (s.c.) administration JNJ-63709178 were evaluated. The i.v. infusions administered once every 2 weeks (cohorts 1-5 [n = 17]) twice weekly 6-11 36]). A twice-weekly s.c. dosing regimen...