A5025409813- Cancer Cells and Metastasis
- HER2/EGFR in Cancer Research
- Cancer Genomics and Diagnostics
- Breast Cancer Treatment Studies
- Cancer Treatment and Pharmacology
- BRCA gene mutations in cancer
- Cancer, Hypoxia, and Metabolism
- Estrogen and related hormone effects
- Cancer Immunotherapy and Biomarkers
- RNA modifications and cancer
- Advanced Breast Cancer Therapies
- Epigenetics and DNA Methylation
- Cancer Research and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Nanoplatforms for cancer theranostics
- Protein Tyrosine Phosphatases
- Cancer-related Molecular Pathways
- Cancer, Stress, Anesthesia, and Immune Response
- Immunotherapy and Immune Responses
- Bioinformatics and Genomic Networks
- Virus-based gene therapy research
- DNA Repair Mechanisms
- Gene expression and cancer classification
- Computational Drug Discovery Methods
- Genetic factors in colorectal cancer
Houston Methodist
2016-2025
German Cancer Research Center
2011-2025
Methodist Hospital
2016-2025
Heidelberg University
2011-2025
Cornell University
2013-2025
University Cancer Center Hamburg
2017-2025
Universität Hamburg
2017-2025
University Medical Center Hamburg-Eppendorf
2017-2025
Methodist Hospital
2012-2024
University of California, Irvine
2018-2024
Tumorigenic breast cancer cells that express high levels of CD44 and low or undetectable CD24 (CD44 > /CD24 >/low ) may be resistant to chemotherapy therefore responsible for relapse. These tumorigenic can isolated from biopsies propagated as mammospheres in vitro. In this study, we aimed test directly human cancers the effect conventional lapatinib (an epidermal growth factor receptor [EGFR]/HER2 pathway inhibitor) on cell population. Paired core were obtained patients with primary before...
Some breast cancers have been shown to contain a small fraction of cells characterized by CD44(+)/CD24(-/low) cell-surface antigen profile that high tumor-initiating potential. In addition, cancer propagated in vitro as mammospheres (MSs) also be enriched for capable self-renewal. this study, we defined gene expression signature common both and MS-forming cells. To examine its clinical significance, determined whether tumor surviving after conventional treatments were bearing...
Abstract Purpose: Genomic profiling studies suggest that triple-negative breast cancer (TNBC) is a heterogeneous disease. In this study, we sought to define TNBC subtypes and identify subtype-specific markers targets. Experimental Design: RNA DNA analyses were conducted on 198 tumors [estrogen receptor (ER) negativity defined as Allred scale value ≤ 2] with >50% cellularity (discovery set: n = 84; validation 114) collected at Baylor College of Medicine (Houston, TX). An external...
Background : We have previously demonstrated that breast cancers associated with inherited BRCA1 and BRCA2 gene mutations differ from each other in their histopathologic appearances of these types differs patients unselected for family history (i.e., sporadic cancers). now conducted a more detailed examination cytologic architectural features tumors. Methods Specimens tumor tissue (5-µm-thick sections) were examined independently by two pathologists, who unaware the case or control subject...
Abstract Breast cancer research is hampered by difficulties in obtaining and studying primary human breast tissue, the lack of vivo preclinical models that reflect patient tumor biology accurately. To overcome these limitations, we propagated a cohort tumors grown epithelium-free mammary fat pad severe combined immunodeficient (SCID)/Beige nonobese diabetic (NOD)/SCID/IL-2γ-receptor null (NSG) mice under series transplant conditions. Both yielded stably transplantable xenografts at...
Sustained and complete inhibition of HER3 its output to PI3K/Akt are required for the optimal antitumor effect therapeutic inhibitors HER2 oncogene. Here, we show that, after tyrosine kinase with lapatinib, there is FoxO3a-dependent up-regulation mRNA protein. Up-regulated was then phosphorylated by residual activity, thus partially maintaining P-Akt limiting action lapatinib. Inhibition siRNA or a neutralizing antibody sensitized HER2+ breast cancer cells xenografts lapatinib both in vitro...
We previously reported the eradication of human epidermal growth factor receptor 2 (HER2)- amplified xenografts in mice by inhibition HER2 pathway with lapatinib and trastuzumab to block all homo- heterodimer signaling as well blockade estrogen (ER) when expressed. In this clinical trial, we sought translate these findings patients using targeted therapy without chemotherapy.Women stages II III HER2-positive breast cancers were eligible. They received once per week (4 mg/kg loading, then...
Abstract Purpose: Accumulating evidence supports the existence of breast cancer stem cells (BCSC), which are characterized by their capacity to self-renew and divide indefinitely resistance conventional therapies. The Notch pathway is important for cell renewal a potential target BCSC-directed therapy. Experimental Design: Using human tumorgraft studies, we evaluated impact gamma secretase inhibitors (GSI) on BCSC population efficacy combining GSI with docetaxel treatment. mouse experimental...
Sacituzumab govitecan (SG), a trophoblast cell surface antigen-2 (Trop-2)-directed antibody-drug conjugate, has demonstrated antitumor efficacy and acceptable tolerability in phase I/II multicenter trial (NCT01631552) patients with advanced epithelial cancers. This report summarizes the safety data from overall population (OSP) data, including additional disease cohorts not published previously.Patients refractory metastatic cancers received intravenous SG (8, 10, 12, or 18 mg/kg) on days 1...
Triple-negative breast cancer (TNBC) is an aggressive form of with no effective targeted therapy. Inducible nitric oxide synthase (iNOS) associated poor survival in patients by increasing tumor aggressiveness. This work aimed to investigate the potential iNOS inhibitors as a therapy for TNBC. We hypothesized that inhibition endogenous would decrease TNBC aggressiveness reducing initiation and metastasis through modulation epithelial-mesenchymal transition (EMT)-inducing factors.iNOS protein...
The enumeration of EpCAM-positive circulating tumor cells (CTCs) has allowed estimation overall metastatic burden in breast cancer patients. However, a thorough understanding CTCs associated with brain metastasis (BCBM) is necessary for early identification and evaluation treatment response to BCBM. Here we report that BCBM enriched distinct sub-population identifiable by their biomarker expression mutational content. Deriving from comprehensive analysis CTC transcriptomes, discovered unique...
A ketogenic diet (KD) is a high-fat, low-carbohydrate that leads to the generation of ketones. While KDs improve certain health conditions and are popular for weight loss, detrimental effects have also been reported. Here, we show mice on two different and, at ages, induce cellular senescence in multiple organs, including heart kidney. This effect mediated through adenosine monophosphate–activated protein kinase (AMPK) inactivation mouse double minute 2 (MDM2) by caspase-2, leading p53...
DNA methylation at cytosine bases (5-methylcytosine, 5mC) is a heritable epigenetic mark regulating gene expression. While enzymes that metabolize 5mC are well-characterized, endogenous signaling molecules regulate machinery have not been described. We report physiological nitric oxide (NO) concentrations reversibly inhibit the demethylases TET and ALKBH2 by binding to mononuclear non-heme iron atom forming dinitrosyliron complex (DNIC) preventing cosubstrates from binding. In cancer cells...
Abstract BACKGROUND Women with metastatic breast carcinoma have a highly variable clinical course and outcome. Intrinsic genetic heterogeneity of the primary tumor may play role in this variability explain it part. Therefore, authors tested hypothesis that characteristics tumors are important determinants prognosis survival patients carcinoma. METHODS The prognostic significance biology for outcome disease was assessed 346 lymph node positive who developed distant, recurrent disease....
Phosphatase and tensin homolog (PTEN) loss or activating mutations of phosphoinositol-3 (PI3) kinase (PIK3CA) may be associated with trastuzumab resistance. Trastuzumab, the humanized human epidermal growth factor receptor 2 (HER2) monoclonal antibody, lapatinib, an receptor/HER2 tyrosine inhibitor, are both established treatments for HER2-overexpressing breast cancers. Understanding cellular response to HER2-targeted therapies is needed tailor identify patients less likely benefit.We...