A5037696116- Advanced Breast Cancer Therapies
- HER2/EGFR in Cancer Research
- Cancer Treatment and Pharmacology
- Cancer Genomics and Diagnostics
- Energy and Environment Impacts
- Cancer Immunotherapy and Biomarkers
- Breast Cancer Treatment Studies
- Estrogen and related hormone effects
- Immunotherapy and Immune Responses
- Glioma Diagnosis and Treatment
- Lung Cancer Treatments and Mutations
- Epigenetics and DNA Methylation
- Phagocytosis and Immune Regulation
- Genetic factors in colorectal cancer
- Esophageal Cancer Research and Treatment
- Ferroptosis and cancer prognosis
- Cancer, Hypoxia, and Metabolism
- Cancer-related Molecular Pathways
- RNA modifications and cancer
- Eosinophilic Esophagitis
- Cancer-related molecular mechanisms research
- Dementia and Cognitive Impairment Research
- PI3K/AKT/mTOR signaling in cancer
- Cancer Risks and Factors
- Neurofibromatosis and Schwannoma Cases
Washington University in St. Louis
2016-2025
Alvin J. Siteman Cancer Center
2020-2025
Sichuan University
2025
Hudson Institute
2024
John Wiley & Sons (United States)
2024
Zoucheng People's Hospital
2023
Cancer Research And Biostatistics
2009-2023
University of Alabama
2023
Duke Medical Center
2023
Jewish Hospital
2022
Abstract Cancer immunotherapy generally offers limited clinical benefit without coordinated strategies to mitigate the immunosuppressive nature of tumor microenvironment. Critical drivers immune escape in microenvironment include tumor-associated macrophages and myeloid-derived suppressor cells, which not only mediate suppression, but also promote metastatic dissemination impart resistance cytotoxic therapies. Thus, ablate effects these myeloid cell populations may offer great therapeutic...
To correlate the variable clinical features of oestrogen-receptor-positive breast cancer with somatic alterations, we studied pretreatment tumour biopsies accrued from patients in two studies neoadjuvant aromatase inhibitor therapy by massively parallel sequencing and analysis. Eighteen significantly mutated genes were identified, including five (RUNX1, CBFB, MYH9, MLL3 SF3B1) previously linked to haematopoietic disorders. Mutant MAP3K1 was associated luminal A status, low-grade histology...
Understanding how tumor response is related to relapse risk would help clinicians make decisions about additional treatment options for patients who have received neoadjuvant endocrine estrogen receptor–positive (ER+) breast cancer. Tumors from 228 postmenopausal women with confirmed ER+ stage 2 and 3 cancers in the P024 therapy trial, which compared letrozole tamoxifen 4 months before surgery, were analyzed posttreatment ER status, Ki67 proliferation index, histological grade, pathological...
To characterize patient-derived xenografts (PDXs) for functional studies, we made whole-genome comparisons with originating breast cancers representative of the major intrinsic subtypes. Structural and copy number aberrations were found to be retained high fidelity. However, at single-nucleotide level, variable numbers PDX-specific somatic events documented, although they only rarely functionally significant. Variant allele frequencies often preserved in PDXs, demonstrating that clonal...
Preoperative aromatase inhibitor (AI) treatment promotes breast-conserving surgery (BCS) for estrogen receptor (ER)-positive breast cancer. To study this option, responses to three AIs were compared in a randomized phase II neoadjuvant trial designed select agents III investigations.Three hundred seventy-seven postmenopausal women with clinical stage ER-positive (Allred score 6-8) cancer randomly assigned receive exemestane, letrozole, or anastrozole. The primary end point was response....
The integration of mass spectrometry-based proteomics with next-generation DNA and RNA sequencing profiles tumors more comprehensively. Here this "proteogenomics" approach was applied to 122 treatment-naive primary breast cancers accrued preserve post-translational modifications, including protein phosphorylation acetylation. Proteogenomics challenged standard cancer diagnoses, provided detailed analysis the ERBB2 amplicon, defined tumor subsets that could benefit from immune checkpoint...
Abstract Age is a significant risk factor for the development of cancer. However, mechanisms that drive age-related increases in cancer remain poorly understood. To determine if senescent stromal cells influence tumorigenesis, we develop mouse model mimics aged skin microenvironment. Using this model, here find are sufficient to localized suppressive myeloid contributed tumour promotion. Further, stromal-derived senescence-associated secretory phenotype interleukin-6 orchestrates both and...
Abstract Purpose: Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor–positive (ER+) breast cancer. This single-arm phase II neoadjuvant trial (NeoPalAna) assessed the antiproliferative activity of CDK4/6 inhibitor palbociclib primary cancer as a prelude to adjuvant studies. Experimental Design: Eligible patients with clinical stage II/III ER+/HER2− received anastrozole 1 mg daily for 4 weeks (cycle 0; goserelin if premenopausal), followed by adding (125 on days...
Purpose To determine the pathologic complete response (pCR) rate in estrogen receptor (ER) –positive primary breast cancer triaged to chemotherapy when protein encoded by MKI67 gene (Ki67) level was > 10% after 2 4 weeks of neoadjuvant aromatase inhibitor (AI) therapy. A second objective examine risk relapse using Ki67-based Preoperative Endocrine Prognostic Index (PEPI). Methods The American College Surgeons Oncology Group (ACOSOG) Z1031A trial enrolled postmenopausal women with stage II...
Male and female glioblastomas are biologically distinct, improving outcomes may require sex-specific approaches to treatment.
Abstract Genetic amplification, mutation, and translocation are known to play a causal role in the upregulation of an oncogene cancer cells. Here, we report emerging microRNA, epigenetic deregulation which may also lead this oncogenic activation. SOX4, belonging SRY-related high mobility group box family, was found be overexpressed (P < 0.005) endometrial tumors (n = 74) compared with uninvolved controls 20). This gene is computationally predicted target miR-129-2. When matched...
The induction of proinflammatory T cells by dendritic cell (DC) subtypes is critical for antitumor responses and effective immune checkpoint blockade (ICB) therapy. Here, we show that human CD1c + CD5 DCs are reduced in melanoma-affected lymph nodes, with expression on correlating patient survival. Activating enhanced priming improved survival after ICB DC numbers increased during therapy, low interleukin-6 (IL-6) concentrations promoted their de novo differentiation. Mechanistically, was...
Triggering receptor expressed on myeloid cells 2 (TREM2) plays important roles in brain microglial function neurodegenerative diseases, but the role of TREM2 GBM TME has not been examined. Here, we found that is highly subsets, including macrophages and microglia human mouse tumors high expression correlates with poor prognosis patients GBM. loss increased interferon-γ–induced immunoactivation, proinflammatory polarization, tumoricidal capacity. In orthotopic models, mice chronic acute Trem2...
Abstract Purpose: A better understanding of the underlying biology invasive serous ovarian cancer is critical for development early detection strategies and new therapeutics. The objective this study was to define gene expression patterns associated with favorable survival. Experimental Design: RNA from 65 cancers analyzed using Affymetrix U133A microarrays. This included 54 stage III/IV cases (30 short-term survivors who lived <3 years 24 long-term >7 years) 11 I/II cases....
Several phosphoinositide 3-kinase (PI3K) catalytic subunit inhibitors are currently in clinical trial. We therefore sought to examine relationships between pharmacologic inhibition and somatic mutations PI3K subunits estrogen receptor (ER)-positive breast cancer, which these particularly common. RNA interference (RNAi) was used determine the effect of selective subunits, p110alpha p110beta, ER(+) cancer cells harboring either mutation (PIK3CA) or gene amplification (PIK3CB). RNAi inhibited...
Although regulatory T (T reg) cells are thought to develop primarily in the thymus, peripheral events that shape protective reg cell population unclear. We analyzed CD4(+) receptor (TCR) repertoire by cellular phenotype and location mice with a fixed TCRbeta chain. found (Foxp3(+)) showed marked skewing of TCR usage anatomical manner similar antigen-experienced (CD44(hi)Foxp3(-)) but not naive (CD44(lo)Foxp3(-)) cells, even though CD44(hi) used mostly dissimilar TCRs. This was likely...
It is often assumed that increases in cancer survival reflect true progress against cancer. This when these are accompanied by decreased burden of disease: Fewer people being diagnosed or dying from (ie, incidence and mortality). But increased can also occur even increasing mortality unchanged. To use trends burden—incidence mortality—to illustrate changes progress. Using data 1975 to 2010 collected the Surveillance, Epidemiology, End Results Program (incidence, survival) National Center for...
Biomarkers for preterm labor (PTL) and delivery can be discovered through the analysis of transcriptome (transcriptomics) protein composition (proteomics). Characterization global changes in low-molecular weight compounds which constitute 'metabolic network' cells (metabolome) is now possible by using a 'metabolomics' approach. Metabolomic profiling has special advantages over transcriptomics proteomics since metabolic network downstream from gene expression synthesis, thus more closely...