A5024886364- AI in cancer detection
- Radiomics and Machine Learning in Medical Imaging
- Cancer Genomics and Diagnostics
- HER2/EGFR in Cancer Research
- Cancer Cells and Metastasis
- Advanced Breast Cancer Therapies
- Monoclonal and Polyclonal Antibodies Research
- PARP inhibition in cancer therapy
- Radiopharmaceutical Chemistry and Applications
- Cancer-related Molecular Pathways
- Lung Cancer Treatments and Mutations
- Cancer, Hypoxia, and Metabolism
- PI3K/AKT/mTOR signaling in cancer
- FOXO transcription factor regulation
- Nuclear Receptors and Signaling
- Cancer-related molecular mechanisms research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cancer Research and Treatments
- Metabolism, Diabetes, and Cancer
- CAR-T cell therapy research
- Microtubule and mitosis dynamics
- Cancer, Lipids, and Metabolism
- Pancreatic and Hepatic Oncology Research
- Molecular Biology Techniques and Applications
- RNA modifications and cancer
The University of Texas MD Anderson Cancer Center
2016-2025
Jackson Laboratory
2023
Advanced Cancer Therapeutics
2016
Baylor College of Medicine
2013
Hamamatsu University School of Medicine
2013
Rice University
2013
The University of Texas Health Science Center at Houston
2013
Orbital ATK (United States)
2001
The epithelial-to-mesenchymal transition (EMT) produces cancer cells that are invasive, migratory, and exhibit stem cell characteristics, hallmarks of have the potential to generate metastases. Inducers EMT include several transcription factors (TFs), such as Goosecoid, Snail, Twist, well secreted TGF-β1. Each these is capable, on its own, inducing an in human mammary epithelial (HMLE) line. However, interactions between regulators poorly understood. Overexpression each above inducers...
Cancer stem cells (CSCs) are a small subpopulation of cancer that have increased resistance to conventional therapies and capable establishing metastasis. However, only few biomarkers CSCs been identified. Here, we report ganglioside GD2 (a glycosphingolipid) identifies fraction in human breast cell lines patient samples forming mammospheres initiating tumors with as 10 GD2+ cells. In addition, the majority also CD44hiCD24lo, previously established CSC-associated surface phenotype. Gene...
Abstract The epithelial-to-mesenchymal transition (EMT) is an embryonic process that becomes latent in most normal adult tissues. Recently, we have shown induction of EMT endows breast epithelial cells with stem cell traits. In this report, further characterized the EMT-derived and these are similar to mesenchymal (MSCs) capacity differentiate into multiple tissue lineages. For purpose, induced by ectopic expression Twist, Snail, or transforming growth factor-β immortalized human mammary...
Resistance to chemotherapy and metastases are the major causes of breast cancer-related mortality. Moreover, cancer stem cells (CSC) play critical roles in progression treatment resistance. Previously, it was found that CSC-like can be generated by aberrant activation epithelial-mesenchymal transition (EMT), thereby making anti-EMT strategies a novel therapeutic option for aggressive cancers. Here, we report transcription factor FOXC2 induced response multiple EMT signaling pathways as well...
Abstract Epithelial–mesenchymal transition ( EMT ) is a critical process providing tumor cells with the ability to migrate and escape from primary metastasize distant sites. Recently, was shown be associated cancer stem cell CSC phenotype in breast cancer. Snail transcription factor that mediates number of types, including colorectal CRC ). Our study done determine role mediating function . Human specimens were stained for expression, human lines transduced retroviral construct or vector...
Oxidative phosphorylation (OXPHOS) is an active metabolic pathway in many cancers. RNA from pretreatment biopsies patients with triple-negative breast cancer (TNBC) who received neoadjuvant chemotherapy demonstrated that the top canonical associated worse outcome was higher expression of OXPHOS signature. IACS-10759, a novel inhibitor OXPHOS, stabilized growth multiple TNBC patient-derived xenografts (PDX). On gene profiling, all sensitive models displayed basal-like 1 subtype. Expression...
Epithelial cancer cells are likely to undergo epithelial-mesenchymal transition (EMT) prior entering the peripheral circulation. By undergoing EMT, circulating tumor (CTCs) lose epithelial markers and may escape detection by conventional methods. Therefore, we conducted a pilot study investigate mRNA transcripts of EMT-inducing transcription factors (TFs) in from blood (PB) patients with primary breast (PBC). PB mononuclear were isolated 52 stages I-III PBC 30 healthy donors (HDs)...
Abstract Purpose: Poor prognosis in triple-negative breast cancer (TNBC) is due to an aggressive phenotype and lack of biomarker-driven targeted therapies. Overexpression cyclin E phosphorylated-CDK2 are correlated with poor survival patients TNBC, the absence CDK2 desensitizes cells inhibition Wee1 kinase, a key cell-cycle regulator. We hypothesize that expression can predict response therapies, which include kinase inhibitor, AZD1775. Experimental Design: Mono- combination therapies...
Abstract Development of candidate cancer treatments is a resource-intensive process, with the research community continuing to investigate options beyond static genomic characterization. Toward this goal, we have established landscapes 536 patient-derived xenograft (PDX) models across 25 types, together mutation, copy number, fusion, transcriptomic profiles, and NCI-MATCH arms. Compared human tumors, PDXs typically higher purity fit dynamic driver events molecular properties via multiple...
Abstract Zanidatamab is a bispecific human epidermal growth factor receptor 2 (HER2)-targeted antibody that has demonstrated antitumor activity in broad range of HER2-amplified/expressing solid tumors. We determined the zanidatamab patient-derived xenograft (PDX) models developed from pretreatment or postprogression biopsies on first-in-human phase I study (NCT02892123). Of 36 tumors implanted, 19 PDX were established (52.7% take rate) 17 patients. Established PDXs represented...
Background Breast cancer patients who are resistant to neoadjuvant chemotherapy (NeoCT) have a poor prognosis. There is pressing need develop in vivo models of chemo tumors test novel therapeutics. We hypothesized that patient-derived breast xenografts (BCXs) from chemo- naïve and chemotherapy-exposed can provide high fidelity for chemoresistant cancers. Methods Patient BCXs were characterized with short tandem repeat DNA fingerprinting, reverse phase protein arrays, molecular inversion...
MDM2/MDMX proteins are frequently elevated in hormone receptor-positive (ER+) breast cancer. We sought to determine the antitumor efficacy of combination ALRN-6924, a dual inhibitor MDM2/MDMX, with chemotherapy ER+ cancer models.
Abstract Purpose: Neratinib is an irreversible, pan-HER tyrosine kinase inhibitor that FDA approved for HER2-overexpressing/amplified (HER2+) breast cancer. In this preclinical study, we explored the efficacy of neratinib in combination with inhibitors downstream signaling HER2+ cancers vitro and vivo. Experimental Design: Cell viability, colony formation assays, Western blotting were used to determine effect vitro. vivo was assessed patient-derived xenografts (PDX): two breast, colorectal,...
Ongoing clinical trials target the aberrant PI3K/Akt/mammalian of rapamycin (mTOR) pathway in breast cancer through administration rapamycin, an allosteric mTOR inhibitor, combination with paclitaxel. However, synergy may not be fully exploited clinically because distinct pharmacokinetic parameters drugs. This study explores synergistic potential site-specific, colocalized delivery and paclitaxel nanoparticle incorporation. Nanoparticle drug loading was accurately controlled, ratios...
We tested the antitumor efficacy of mTOR catalytic site inhibitor MLN0128 in models with intrinsic or acquired rapamycin-resistance. Cell lines that were intrinsically rapamycin-resistant as well those rapamycin-sensitive sensitive to vitro. inhibited both mTORC1 and mTORC2 signaling, more robust inhibition downstream 4E-BP1 phosphorylation cap-dependent translation compared rapamycin Rapamycin-sensitive BT474 cell line resistance (BT474 RR) prolonged treatment This an mutation (S2035F)...
Selinexor (KPT-330) is an oral agent that has been shown to inhibit the nuclear exporter XPO1. Given pressing need for novel therapies triple-negative breast cancer (TNBC), we sought determine antitumor effects of selinexor in vitro and vivo.Twenty-six cell lines different subtypes were treated with vitro. Cell proliferation assays used measure half-maximal inhibitory concentration (IC50) test combination chemotherapy. In vivo efficacy was tested both as a single therapy TNBC patient-derived...
Background: Breast cancer patients who do not respond to neoadjuvant therapy have a poor prognosis. There is pressing need for novel targets and models preclinical testing. Here we report characterization of breast patient-derived xenografts (PDX) largely generated from residual tumors following chemotherapy.Experimental Design: PDXs were derived surgical samples primary or locally recurrent tumors. Normal tumor DNA sequencing, RNASeq, reverse phase protein arrays (RPPA) performed....
Abstract Although patient-derived xenografts (PDX) are commonly used for preclinical modeling in cancer research, a standard approach to vivo tumor growth analysis and assessment of antitumor activity is lacking, complicating the comparison different studies determination whether PDX experiment has produced evidence needed consider new therapy promising. We present consensus recommendations activity, providing public access suite tools analyses. expect that harmonizing study design assessing...
Abstract Purpose: Cyclin E (CCNE1) has been proposed as a biomarker of sensitivity to adavosertib, Wee1 kinase inhibitor, and mechanism resistance HER2-targeted therapy. Experimental Design: Copy number genomic sequencing data from The Cancer Genome Atlas MD Anderson Center databases were analyzed assess ERBB2 CCNE1 expression. Molecular characteristics tumors patient-derived xenografts (PDX) assessed by next-generation sequencing, whole-exome fluorescent in situ hybridization, IHC. In...