A5080595793- Cancer-related Molecular Pathways
- RNA modifications and cancer
- Bone health and treatments
- Bone Metabolism and Diseases
- Cancer Genomics and Diagnostics
- Protein Degradation and Inhibitors
- Acute Myeloid Leukemia Research
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Bone Tumor Diagnosis and Treatments
- DNA Repair Mechanisms
- Cell death mechanisms and regulation
- Lung Cancer Treatments and Mutations
- RNA Research and Splicing
- Cancer-related gene regulation
- Acute Lymphoblastic Leukemia research
- Molecular Biology Techniques and Applications
- Kruppel-like factors research
- Insect Resistance and Genetics
- MicroRNA in disease regulation
- Heat shock proteins research
- Nutrition, Genetics, and Disease
- PI3K/AKT/mTOR signaling in cancer
- Chemokine receptors and signaling
- Renal and related cancers
The University of Texas MD Anderson Cancer Center
2014-2025
The University of Texas Health Science Center at Houston
2022-2023
ONC201 triggers an apoptotic cellular stress response in both solid and blood tumors.
Early clinical trials using murine double minute 2 (MDM2) inhibitors demonstrated proof-of-concept of p53-induced apoptosis by MDM2 inhibition in cancer cells; however, not all wild-type TP53 tumors are sensitive to inhibition. Therefore, more potent and biomarkers predictive tumor sensitivity needed. The novel inhibitor DS-3032b is 10-fold than the first-generation nutlin-3a. mutations were resistance DS-3032b, allele frequencies negatively correlated with DS-3032b. However, varied greatly....
Abstract The majority of TP53 missense mutations identified in cancer patients are the DNA-binding domain and characterized as either structural or contact mutations. These exhibit inhibitory effects on wild-type p53 activity. More importantly, these also demonstrate gain-of-function (GOF) activities by increased metastasis, poor prognosis, drug resistance. To better understand which mutations, Li–Fraumeni syndrome, contribute to tumorigenesis, we generated mice harboring a novel germline...
Abstract The ataxia telangiectasia and RAD3-related (ATR) kinase functions with mutated (ATM) as a modulator of DNA damage response (DDR). We assessed the antitumor effects ATR inhibitor elimusertib (BAY 1895344) in patient-derived xenograft (PDX) models DDR alterations. Antitumor activity was by change tumor volume (TV) from baseline. Responses were categorized follows: partial (PR): >30% decrease TV; >20% increase TV: progressive disease (PD); non-PR/PD: stable (SD)....
Curing patients with acute myeloid leukemia (AML) remains a therapeutic challenge. The polycomb complex protein B-cell-specific Moloney murine virus integration site 1 (BMI-1) is required for the self-renewal and maintenance of stem cells. We investigated prognostic significance BMI-1 in AML effects novel small molecule selective inhibitor BMI-1, PTC-209. expression was determined 511 newly diagnosed together 207 other proteins using reverse-phase array technology. Patients unfavorable...
BH3 profiling measures the propensity of transformed cells to undergo intrinsic apoptosis and is determined by exposing BH3-mimicking peptides. We hypothesized that basal levels prosurvival BCL-2 family proteins may modulate predictive power termed it mitochondrial profiling. investigated correlation between cell sensitivity apoptogenic agents profiling, using a panel acute myeloid leukemias induced exposure cytarabine, mimetic ABT-199, MDM2 inhibitor Nutlin-3a, or CRM1 KPT-330. found...
Alterations of the tumor suppressor TP53 , one most common events in cancer, alone are insufficient for development but serve as drivers transformation. We sought to identify cooperating through genomic analyses a somatic Trp53 R245W mouse model (equivalent R248W hot spot mutation human cancers) that recapitulates metastatic breast–cancer development. identified lesions similar those found breast cancers. Moreover, we activation Pi3k/Akt/mTOR pathway tumors via mutations Pten Erbb2 Kras...
Abstract Missense mutations in the DNA binding domain of p53 are characterized as structural or contact based on their effect conformation protein. These show gain-of-function (GOF) activities, such promoting increased metastatic incidence compared with loss, often mediated by interaction mutant a set transcription factors. interactions largely context specific. To understand mechanisms which drive osteosarcoma progression, we created mouse models, either p53R172H p53R245W expressed...
Dead-End (DND1) is an RNA-binding protein involved in translational regulation. Defects DND1 gene causes germ cell tumors and sterility rodents. Experimental studies with human somatic cancer cells indicate that has anti-proliferative pro-apoptotic function some while oncogenic other cells. We examined The Cancer Genome Atlas data for alterations expression changes a variety of cancers. found amplified, deleted or mutated multiple In different cancers, alteration correlates increased...
Abstract Ductal carcinoma in situ (DCIS) is an early breast neoplasm that may, but does not always, progress to invasion. It difficult predict if DCIS will become invasive. Treatment includes surgical removal and radiation. To avoid overtreatment, a strategy needed stratify tumors likely spread from those remain indolent. The Lozano lab created somatic mouse model with conditional p53R245W mutation the mammary epithelium, resulting tumorigenesis. Pathological analysis identified both...
<div>Abstract<p>Missense mutations in the DNA binding domain of p53 are characterized as structural or contact based on their effect conformation protein. These show gain-of-function activities, such promoting increased metastatic incidence compared to loss, often mediated by interaction mutant with a set transcription factors. interactions largely context specific. In order understand mechanisms which drive osteosarcoma progression, we created mouse models, either p53R172H...
<p>Supplementary Figures 1-6 with figure legends</p>