A5089088029- Metabolism, Diabetes, and Cancer
- Cancer, Hypoxia, and Metabolism
- Pancreatic function and diabetes
- Cancer-related Molecular Pathways
- PI3K/AKT/mTOR signaling in cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- PARP inhibition in cancer therapy
- Inflammation biomarkers and pathways
- Stroke Rehabilitation and Recovery
- 3D Printing in Biomedical Research
- HER2/EGFR in Cancer Research
- Epigenetics and DNA Methylation
- Neurotransmitter Receptor Influence on Behavior
- Receptor Mechanisms and Signaling
- Cancer Cells and Metastasis
- Peptidase Inhibition and Analysis
- Amino Acid Enzymes and Metabolism
- Cancer Genomics and Diagnostics
- Cancer, Lipids, and Metabolism
- Click Chemistry and Applications
- Bacteriophages and microbial interactions
- Metal complexes synthesis and properties
- Nanoplatforms for cancer theranostics
- S100 Proteins and Annexins
- Chemotherapy-induced cardiotoxicity and mitigation
Revolution Medicines (United States)
2025
Sanford Research
2011-2024
Mayo Clinic
2018-2022
WinnMed
2021-2022
Sanford Health
2011-2013
University of South Dakota
2008-2011
Triple-negative breast cancer (TNBC) is a heterogeneous disease with poor prognosis that lacks targeted therapies, especially in patients chemotherapy-resistant disease. Since DNA methylation-induced silencing of tumor suppressors common cancer, reversal promoter hypermethylation by 5-aza-2'-deoxycytidine (decitabine), an FDA-approved methyltransferase (DNMT) inhibitor, has proven effective treating hematological neoplasms. However, its antitumor effect varies solid tumors, stressing the...
Background: The antihyperglycemic drug metformin may have beneficial effects on the prevention and treatment of cancer. Metformin is known to activate AMP-activated protein kinase (AMPK). It has also been shown inhibit cyclin D1 expression proliferation some cultured cancer cells. However, mechanisms action by which mediates cell cycle arrest are not completely understood.Results: In this study, was found most breast lines. This independent estrogen receptor, HER2, or p53 status. Inhibition...
Different cancer cells exhibit altered sensitivity to metformin treatment. Recent studies suggest these findings may be due in part the common cell culture practice of utilizing high glucose, and when glucose is lowered, becomes increasingly cytotoxic cells. In low conditions ranging from 0 5 mM, was breast lines MCF7, MDAMB231 SKBR3, ovarian OVCAR3, PA-1. SKBR3 were previously shown resistant normal medium. When increased 10 mM or above, all become less responsive Metformin treatment...
The discovery of elironrasib (RMC-6291) represents a significant breakthrough in targeting the previously deemed undruggable GTP-bound, active KRASG12C. To target state RAS (RAS(ON)) directly, we have employed an innovative tri-complex inhibitor (TCI) modality involving formation complex with inhibitor, intracellular chaperone protein CypA, and KRASG12C its GTP-bound form. resulting inhibits oncogenic signaling, inducing tumor regressions across various preclinical models mutant human...
There is substantial evidence that metformin, a drug used to treat type 2 diabetics, potentially useful as therapeutic agent for cancer. However, better understanding of the molecular mechanisms through which metformin promotes cell-cycle arrest and cell death cancer cells necessary. It will also be important understand how response tumor differs from normal why some are resistant effects metformin. We have found exposure induces in all but one line, MDA-MB-231, panel breast lines. MCF10A...
Article15 January 2018Open Access Source Data Differential roles of ERRFI1 in EGFR and AKT pathway regulation affect cancer proliferation Junmei Cairns orcid.org/0000-0002-3941-4564 Department Molecular Pharmacology Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA Search for more papers by this author Brooke L Fridley Health Sciences Research, Biostatistics Bioinformatics, Moffitt Cancer Center, Tampa, FL, Gregory D Jenkins Yongxian Zhuang Jia Yu Liewei Wang Corresponding Author...
Neoadjuvant chemotherapy (NAC) remains the cornerstone of treatment for triple negative breast cancer (TNBC), with goal complete eradication disease. However, patients residual disease after NAC, recurrence and mortality rates are high identification novel therapeutic targets is urgently needed. We quantified tyrosine phosphorylation (pTyr)-mediated signaling networks in sensitive (CS) resistant (CR) TNBC patient-derived xenografts (PDX), to gain insights. The antitumor activity SFK...
Trastuzumab (Herceptin) is the key systemic therapy for HER2-positive breast cancer. However, initial response rate limited to approximately 50% in patients. Moreover, most patients, especially at an advanced stage, eventually develop acquired resistance. Understanding mechanisms of trastuzumab resistance crucial achieving better treatment outcome this group patients.A trastuzumab-resistant (TR) cell line was developed using BT474 cancer line. Whole-transcriptome expression array performed...
Approximately one‐third of patients with metastatic castration‐resistant prostate cancer (CRPC) exhibited primary abiraterone resistance. To identify alternative treatment for nonresponders, we performed drug discovery analyses using the L1000 database differentially expressed genes identified in tumor biopsies and patient‐derived xenograft (PDX) tumors between responders nonresponders enrolled PROMOTE trial. This approach 3 drugs, including topoisomerase II (TOP2) inhibitor mitoxantrone,...
Historically, the clinical utility of oncolytic virotherapy as a treatment for wide range cancer types was first demonstrated by three pilot human trials conducted in Japan 1970s and 1980s using wild-type Urabe mumps virus (MuV) isolate. Using sample actual original MuV trial stock (MuV-U-Japan) used these Japanese trials, we found that MuV-U-Japan consisted variety very closely related MuVs differed an average only amino acids. Two isolates, MuV-UA MuV-UC, potently killed panel established...
The role of tumor protein D54 in breast cancer has not been studied and its function remains unclear. In our previous pharmacogenomic studies using lymphoblastoid cell line (LCL), this identified to affect metformin response. Although widely as a prophylactic chemotherapeutic drug, there is still lack biomarkers predicting the response cancer. study, we revealed novel TPD54 through understanding how altered sensitivity metformin. altering cellular treatment was carried out by either...
Elevated glucose uptake and production of lactate are common features cancer cells. Among many tumor-promoting effects, inhibits immune responses is positively correlated with radioresistance. Dichloroacetate (DCA) an inhibitor pyruvate dehydrogenase kinase that decreases production. Quercetin a flavonoid compound found in fruits vegetables export. We investigated the potential role mechanisms DCA, quercetin, their combination, treatment HPV-positive head neck squamous cell carcinoma,...
Anastrozole is a widely prescribed aromatase inhibitor for the therapy of estrogen receptor positive (ER+) breast cancer. We performed genome-wide association study (GWAS) plasma anastrozole concentrations in 687 postmenopausal women with ER+ The top single-nucleotide polymorphism (SNP) signal mapped across SLC38A7 (rs11648166, P = 2.3E-08), which we showed to encode an influx transporter. second most significant (rs28845026, 5.4E-08) near ALPPL2 and displayed epistasis signal. Both these...
Abstract The application of patient-derived xenografts (PDX) in drug screening and testing is a costly time-consuming endeavor. While cell lines permit extensive mechanistic studies, many human breast cancer lack patient characteristics clinical treatment information. Establishing that retain patient’s genetic response information would enable greater studies. Therefore, we utilized PDX from the Mayo Breast Cancer Genome Guided Therapy Study (BEAUTY) to establish two immortalized,...
Of the deaths attributed to cancer, 90% are due metastasis. Treatments that prevent or cure metastasis remain elusive. Low expression of extracellular superoxide dismutase (EcSOD SOD3) has been associated with poor outcomes and increased metastatic potential in multiple types cancer. Here, we characterize antimetastatic therapeutic mechanisms a macromolecular SOD3-mimetic polynitroxyl albumin (PNA, also known as VACNO). PNA is human serum conjugated nitroxide groups acts an SOD-mimetic. Here...
Novel therapeutic strategies for Alzheimer's disease (AD) are of the greatest priority given consistent failure recent clinical trials focused on Aβ or pTau. Earlier, we demonstrated that mild mitochondrial complex I inhibitor CP2 blocks neurodegeneration and cognitive decline in multiple mouse models AD. To evaluate safety humans, performed a genome-wide association study (GWAS) using 196 lymphoblastoid cell lines identified 11 SNP loci 64 mRNA expression probe sets potentially associate...
Background Nicotinamide adenine dinucleotide (NAD+) is vital for not only energy metabolism but also signaling pathways. A major source of NAD+ depletion the activation poly (ADP-ribose) polymerase (PARP) in response to DNA damage. We have previously demonstrated that metformin can cause both caspase-dependent cell death and PARP-dependent MCF7 breast cancer cells MDA-MB-231 (231) while high-glucose media. hypothesize via PARP contributes caused by metformin. phosphoribosyltransferase...
Background Metformin has been shown to inhibit cell proliferation and induce death in many cancer lines. However, some lines exhibit resistance the cytotoxic effects of metformin tissue culture medium with high glucose levels (25 mM). Recent studies suggest when is lowered; becomes increasingly cells. precise mechanism for metformin’s cytotoxicity remains unidentified.
Abstract Triggering receptor expressed on myeloid cell 2 (TREM2) is a surface that, in the central nervous system, exclusively microglia. TREM2 variants have been linked to increased risk for neurodegenerative diseases, but functional effects of microglial remain largely unknown. To this end, we investigated TAR-DNA binding protein 43 kDa (TDP-43)-related disease via viral-mediated expression human TDP-43 (hTDP-43) mice or inducible hTDP43 with defective nuclear localization signals...