- Breast Cancer Treatment Studies
- Cancer Genomics and Diagnostics
- Colorectal Cancer Treatments and Studies
- HER2/EGFR in Cancer Research
- Lung Cancer Treatments and Mutations
- Cancer Cells and Metastasis
- Genetic factors in colorectal cancer
- Estrogen and related hormone effects
- Cancer Immunotherapy and Biomarkers
- NF-κB Signaling Pathways
- Advanced Breast Cancer Therapies
- RNA modifications and cancer
- PARP inhibition in cancer therapy
- Gastric Cancer Management and Outcomes
- Cytokine Signaling Pathways and Interactions
- Ferroptosis and cancer prognosis
- Breast Lesions and Carcinomas
- Immune cells in cancer
- BRCA gene mutations in cancer
- Monoclonal and Polyclonal Antibodies Research
- Inflammatory mediators and NSAID effects
- Lymphoma Diagnosis and Treatment
- CAR-T cell therapy research
- Cancer Research and Treatments
- Prostate Cancer Treatment and Research
Mayo Clinic
2024-2025
University of Pittsburgh
2015-2024
NRG Oncology
2018-2024
UPMC Hillman Cancer Center
2015-2024
NSABP Foundation
2018-2024
Mayo Clinic in Florida
2024
University of Minnesota Rochester
2024
WinnMed
2024
Mayo Clinic in Arizona
2024
University of Michigan–Ann Arbor
2006-2023
Wnts are secreted signaling proteins that regulate developmental processes. Here we show Wnt signaling, likely mediated by Wnt-10b, is a molecular switch governs adipogenesis. maintains preadipocytes in an undifferentiated state through inhibition of the adipogenic transcription factors CCAAT/enhancer binding protein alpha (C/EBPalpha) and peroxisome proliferator- activated receptor gamma (PPARgamma). When prevented overexpression Axin or dominant-negative TCF4, these cells differentiate...
Poly(adenosine diphosphate–ribose) polymerase inhibitors target cancers with defects in homologous recombination repair by synthetic lethality. New therapies are needed to reduce recurrence patients BRCA1 or BRCA2 germline mutation–associated early breast cancer.
Nod1 is an Apaf-1-like molecule composed of a caspase-recruitment domain (CARD), nucleotide-binding domain, and leucine-rich repeats that associates with the CARD-containing kinase RICK activates nuclear factor κB (NF-κB). We show self-association mediates proximity interaction γ subunit IκB (IKKγ). Similarly, RICK-related RIP associated via its intermediate region IKKγ. A mutant form IKKγ deficient in binding to IKKα IKKβ inhibited NF-κB activation induced by or RIP. Enforced...
At least two distinct recurrent chromosomal translocations have been implicated in the pathogenesis of MALT lymphoma. The first, t(1;14), results transfer entireBcl10 gene to chromosome 14 wherein Bcl10 expression is inappropriately stimulated by neighboring Ig enhancer. second, t(11;18), synthesis a novel fusion protein, API2-MALT1. Until now, no common mechanism action has proposed explain how products these seemingly unrelated may contribute same malignant process. We show here that and...
Phosphoenolpyruvate carboxykinase (PEPCK) governs the rate-limiting step in gluconeogenesis. Glucocorticoids and adenosine 3′,5′-monophosphate (cAMP) increase PEPCK gene transcription gluconeogenesis, whereas insulin has opposite effect. Insulin is dominant, since it prevents cAMP glucocorticoid-stimulated transcription. Glucocorticoid response elements have been located now a 15-base pair insulin-responsive sequence (IRS) described. Evidence for binding activity that recognizes this presented.
Wnt is a family of secreted signaling proteins that regulate diverse developmental processes. Activation canonical by Wnt10b inhibits differentiation preadipocytes in vitro. To determine whether blocks adipogenesis vivo, we created transgenic mice which expressed from the FABP4 promoter. Expression adipose impairs development this tissue throughout body, with decline ∼50% total body fat and reduction ∼60% weight epididymal perirenal depots. FABP4-Wnt10b resist accumulation when fed high...
Given the clinical relevance of ESR1 mutations as potential drivers resistance to endocrine therapy, this study used sensitive detection methods determine frequency in primary and metastatic breast cancer, cell-free DNA (cfDNA).Six (K303R, S463P, Y537C, Y537N, Y537S, D538G) were assessed by digital droplet PCR (ddPCR), with lower limits 0.05% 0.16%, tumors (n = 43), bone 12) brain metastases 38), cfDNA 29). Correlations between lesions single (1 patient) or serial blood draws (4 patients)...
Abstract Low-passage, serum-free cell lines cultured from patient tumour tissue are the gold-standard for preclinical studies and cellular investigations of glioblastoma (GBM) biology, yet entrenched, poorly-representative line models still widely used, compromising significance much GBM research. We submit that greater adoption these critical resources will be promoted by provision a suitably-sized, meaningfully-described reference collection along with appropriate tools working them....
<h3>Importance</h3> Total neoadjuvant therapy (TNT) is often used to downstage locally advanced rectal cancer (LARC) and decrease locoregional relapse; however, more than one-third of patients develop recurrent metastatic disease. As such, novel combinations are needed. <h3>Objective</h3> To assess whether the addition pembrolizumab during after chemoradiotherapy can lead an improvement in (NAR) score compared with treatment FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) alone. <h3>Design,...
Abstract Background: The benefit of adjuvant regional nodal irradiation including the chest wall after mastectomy (CWI+RNI) and with whole breast (WBI+RNI) conserving surgery (BCS) is well established in pts pathologically positive axillary nodes (pN+). Pts who present node involvement (cN+), receive neoadjuvant chemotherapy (NC), are found to be node-negative at (ypN0), have lower loco-regional recurrence (LRR) rates compared those remain node-positive (ypN+). This phase III, randomized...
5 Background: For patients (pts) with colon cancer (CC), the detection of circulating tumor DNA (ctDNA) is associated persistent disease after resection and outperforms traditional clinical pathological features in prognosticating recurrence risk. We hypothesized that for pts low-risk stage II CC, a positive ctDNA status may identify those who benefit from adjuvant chemotherapy. Methods: In this prospective phase II/III trial, resected CC without high risk whom evaluating oncologist deems...
α-Methylacyl-CoA racemase (AMACR) is a mitochondrial and peroxisomal enzyme involved in the metabolism of branched-chain fatty acid bile intermediates. Recently, AMACR has been demonstrated to be over-expressed localized metastatic prostate cancer, suggesting that it may an important tumor marker. This study examines expression variety human cancers their precursor lesions. A survey online Expressed Sequence Tags (ESTs) Serial Analysis Gene Expression (SAGE) databases revealed was multiple...
The rate of transcription the hepatic phosphoenolpyruvate carboxykinase (PEPCK) and insulin-like growth factor-binding protein 1 (IGFBP-1) genes is stimulated by glucocorticoids inhibited insulin. In both cases, effect insulin dominant, since it suppresses basal glucocorticoid-stimulated PEPCK or IGFBP-1 gene transcription. Analyses promoters transfection IGFBP-1-chloramphenicol acetyltransferase fusion into rat hepatoma cells has led to identification response sequences (IRSs) in genes....
Angiotensin II (Ang II) is a peptide hormone that, like many cytokines, acts as proinflammatory agent and growth factor. After injury to the liver, assists in tissue repair by stimulating hepatocytes hepatic stellate cells synthesize extracellular matrix proteins secrete secondary cytokines myofibroblasts proliferate. However, under conditions of chronic liver injury, all these effects conspire promote pathologic fibrosis. Much this effect Ang results from activation NF-kappaB transcription...
Breast cancer patients have benefited from the use of targeted therapies directed at specific molecular alterations. To identify additional opportunities for therapy, we searched genes with marked overexpression in subsets tumors across a panel breast profiling studies comprising 3,200 microarray experiments. In addition to prioritizing ERBB2, found AGTR1, angiotensin II receptor type I, be markedly overexpressed 10-20% cases multiple independent patient cohorts. Validation experiments...
Patients with breast cancer (BrCa) brain metastases (BrM) have limited therapeutic options. A better understanding of molecular alterations acquired in BrM could identify clinically actionable metastatic dependencies.
Proper regulation of nuclear factor κB (NF-κB) transcriptional activity is required for normal lymphocyte function, and deregulated NF-κB signaling can facilitate lymphomagenesis. We demonstrate that the API2-MALT1 fusion oncoprotein created by recurrent t(11;18)(q21;q21) in mucosa-associated lymphoid tissue (MALT) lymphoma induces proteolytic cleavage NF-κB-inducing kinase (NIK) at arginine 325. NIK requires concerted actions both partners generates a C-terminal fragment retains resistant...
Bone metastases (BoM) are a significant cause of morbidity in patients with estrogen receptor–positive (ER-positive) breast cancer; yet, characterizations human specimens limited. In this study, exome-capture RNA sequencing (ecRNA-seq) on aged (8–12 years), formalin-fixed, paraffin-embedded (FFPE), and decalcified cancer was evaluated. Gene expression values ecRNA-seq quality metrics from FFPE or tumor showed minimal differences when compared matched flash-frozen nondecalcified tumors. then...