A5044158880- Prostate Cancer Treatment and Research
- Hormonal and reproductive studies
- PARP inhibition in cancer therapy
- Cancer Immunotherapy and Biomarkers
- HER2/EGFR in Cancer Research
- Immunotherapy and Immune Responses
- Cytokine Signaling Pathways and Interactions
- Neutropenia and Cancer Infections
- Acute Myeloid Leukemia Research
- Cancer Treatment and Pharmacology
- Lung Cancer Treatments and Mutations
- Cervical Cancer and HPV Research
- Cancer Genomics and Diagnostics
- Cancer therapeutics and mechanisms
- PI3K/AKT/mTOR signaling in cancer
- Cell Adhesion Molecules Research
- DNA Repair Mechanisms
- Radiopharmaceutical Chemistry and Applications
- Inflammatory Biomarkers in Disease Prognosis
- Monoclonal and Polyclonal Antibodies Research
- Glioma Diagnosis and Treatment
- Protein Kinase Regulation and GTPase Signaling
- Breast Cancer Treatment Studies
- Cancer Cells and Metastasis
- Epigenetics and DNA Methylation
The Barbara Ann Karmanos Cancer Institute
2015-2025
Wayne State University
2016-2025
Johannes Gutenberg University Mainz
2025
Michigan United
2015-2020
University of Nicosia
2013
University of Virginia
2003-2009
Ulrich Medical (Germany)
2009
Elisa (Finland)
2009
University of Virginia Health System
2003-2005
Hôpital Paul-Brousse
2004
Abstract Purpose: Incapacitating symptom burden in cancer patients contributes to poor quality of life (QOL) and can influence treatment outcomes because tolerance therapy. In this study, the role circulating cytokines production symptoms is evaluated. Experimental Design: Eighty with metastatic colorectal either normal (group I, n = 40) or dampened II, 24-hour rest/activity patterns measured by actigraphy were identified. Actigraphy correlated QOL indices, serum cortisol obtained at 8:00...
When co-overexpressed, the epidermal growth factor receptor (EGFR) and c-Src cooperate to cause synergistic increases in EGF-induced DNA synthesis, soft agar colony growth, tumor formation nude mice. This synergy is dependent upon c-Src-mediated phosphorylation of a unique tyrosine on EGFR, namely, 845 (Y845). Phenylalanine substitution Y845 (Y845F) was found inhibit synthesis without affecting catalytic activity or its ability phosphorylate Shc activate mitogen-activated protein kinase....
Co-overexpression of the epidermal growth factor (EGF) receptor (EGFR) and c-Src frequently occurs in human tumors is linked to enhanced tumor growth. In experimental systems this synergistic requires EGF-dependent association with EGFR phosphorylation Tyr-845 by c-Src. A search for signaling mediators Tyr(P)-845 revealed that mitochondrial cytochrome c oxidase subunit II (CoxII) binds a Tyr(P)-845- manner. cells involves translocation mitochondria, but regulation process ill-defined. The...
Epidermal growth factor receptor (EGFR) is overexpressed in many cancer types including ~30% of breast cancers. Several small molecule tyrosine kinase inhibitors (TKIs) targeting EGFR have shown clinical efficacy lung and colon cancers, but no benefit has been noted cancer. Thirteen expressing cell lines were analyzed for response to TKIs. Seven found be TKI resistant; while shRNA knockdown determined that four these retained the requirement protein expression growth. Interestingly,...
During development, the mammary gland undergoes extensive remodeling driven by stem cells. Breast cancers are also hierarchically organized and cancer cells characterized CD44+CD24low/− or aldehyde dehydrogenase (ALDH) expression. These markers identify mesenchymal epithelial populations both capable of tumor initiation. Less is known about these in non-cancerous glands. From RNA sequencing, ALDH+ ALDH−CD44+CD24− human have epithelial-like mesenchymal-like characteristics, respectively, with...
Purpose Black/African American (AA) women are twice as likely to be diagnosed with triple negative breast cancer (TNBC) compared whites, an aggressive subtype associated poor prognosis. There no routinely used targeted clinical therapies for TNBC; thus there is a clear need identify prognostic markers and potential therapeutic targets. Methods We evaluated expression of 27,016 genes in 155 treatment-naïve TN tumors from AA Detroit. Associations survival were using Cox proportional hazards...
PARP is essential for recognition and repair of DNA damage. In preclinical models, inhibitors modulate topoisomerase I inhibitor-mediated This phase study determined the MTD, dose-limiting toxicities (DLT), pharmacokinetics (PK), pharmacodynamics (PD) veliparib, an orally bioavailable PARP1/2 inhibitor, in combination with irinotecan.
Overexpression of the epidermal growth factor receptor (EGFR) and its association with tyrosine kinase, c-Src, is correlated increased cellular proliferation tumorigenesis. Previous studies have shown that EGFR c-Src co-overexpression leads to c-Src-mediated phosphorylation 845 mutation Tyr<sup>845</sup> ablates (EGF)-induced DNA synthesis. Here, we investigate contribution signal transducers activators transcription (STAT5b) in signaling pathways regulated by overexpression human breast...
Abstract Breast cancers are not responsive to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), although 30% of breast overexpress EGFR. The mechanism intrinsic resistance EGFR TKIs in cancer is the focus current studies. Here, we observed that remains phosphorylated cells proliferate presence TKIs. In one such cell line, SUM229, inhibiting c-Src activity with either a dominant-negative or TKI decreased phosphorylation on Tyr845, Tyr992, and Tyr1086 Conversely,...
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown clinical efficacy in lung, colon, and pancreatic cancers. In lung cancer, resistance to EGFR TKIs correlates with amplification of the hepatocyte (HGF) Met. Breast cancers do not respond TKIs, even though is overexpressed. This intrinsic breast cancer does correlate Met amplification. several tissue monoculture models human Met, although expressed, phosphorylated, suggesting a requirement for...
Breast cancers show a lack of response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), despite 30% tumors expressing EGFR. The mechanism this resistance is unknown; however, we have recently shown that Met activity compensates for loss EGFR in cell culture models. has been implicated the pathogenesis breast and therefore may cooperate with tumor growth. Here found phosphorylation proliferation part regulated by expression. In addition, constitutive occurred...
Abstract Purpose: AZD1775 is a first-in-class Wee1 inhibitor with dual function as DNA damage sensitizer and cytotoxic agent. A phase I study of for solid tumors suggested activity against brain tumors, but preclinical indicated minimal blood–brain barrier penetration in mice. To resolve this controversy, we examined the pharmacokinetics pharmacodynamics patients first-recurrence, glioblastoma. Patients Methods: Twenty adult received single dose prior to tumor resection enrolled either...
Activation of the epidermal growth factor receptor (EGFR) regulates cellular proliferation, survival, and migration breast cancer cells. In particular, EGFR recruits signaling proteins to cell membrane leading their phosphorylation activation. However, also localizes other structures, including endosomes, mitochondrion, nuclei. Recently, we demonstrated that lipid raft localization in triple-negative lines promotes protein-dependent, kinase-independent activation Akt. Here, further define...
There is a vital need for improved therapeutic strategies that are effective in both primary and metastatic triple-negative breast cancer (TNBC). Current treatment options TNBC patients restricted to chemotherapy; however tyrosine kinases promising druggable targets due their high expression multiple subtypes. Since coexpression of receptor (RTKs) can promote signaling crosstalk cell survival the presence kinase inhibitors, it likely RTKs will be inhibited enhance benefit prevent resistance....
Matriptase is an epithelia-specific membrane-anchored serine protease that has received considerable attention in recent years because of its consistent dysregulation human epithelial tumours, including breast cancer. Mice with reduced levels matriptase display a significant delay oncogene-induced mammary tumour formation and blunted growth. The abated growth associated decrease cancer cell proliferation. Here we demonstrate by genetic deletion silencing the proliferation impairment...
Abstract Among breast cancer patients, those diagnosed with the triple-negative (TNBC) subtype have worst prog-nosis. TNBC does not express estrogen receptor-alpha, progesterone receptor, or HER2 oncogene; therefore, lacks targets for molecularly-guided therapies. The concept that EGFR oncogene inhibitor drugs could be used as targeted treatment against has been put forth based on estimates 30–60% of high levels EGFR. However, results from clinical trials testing inhibitors, alone in...
Signaling networks play important roles in cancer progression. For example, overexpression of the epidermal growth factor receptor (EGFR) is a poor prognostic indicator multiple tumor types. Recent studies have postulated that EGFR functions as central conduit for signaling by different classes cell surface receptors. In this study, we demonstrated c-Src-dependent phosphorylation tyrosine 845 (Tyr 845) on was required DNA synthesis induced G protein-coupled agonists, endothelin (ET) and...
Abstract We have recently shown that an amphiregulin-mediated autocrine loop is responsible for growth factor–independent proliferation, motility, and invasive capacity of some aggressive breast cancer cells, such as the SUM149 cell line. In present study, we investigated mechanisms by which amphiregulin activation epidermal factor receptor (EGFR) regulates these altered phenotypes. Bioinformatic analysis gene expression networks regulated implicated interleukin-1α (IL-1α) IL-1β key...
Abstract Sipuleucel-T is an autologous cellular immunotherapy that targets prostatic acid phosphatase (PAP) and available for treatment of men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). In this single-arm, two-cohort, multicenter clinical study, potential racial differences in immune responses to sipuleucel-T mCRPC were explored. Patients’ blood samples obtained assess serum cytokines, humoral responses, immunity markers before after...
Phosphorylation of epidermal growth factor receptor (EGFR) on tyrosine 845 by c-Src has been shown to be important for cell proliferation and migration in several model systems. This cross talk between EGFR Src family kinases (SFKs) is one mechanism resistance inhibitors both models the clinic. Here, we show that phosphorylation required transformation using breast cancer. Overexpression EGFR-Y845F or treating cells with SFK inhibitor dasatinib abrogated phosphorylation, yet had little no...
Abstract Triple-negative breast cancer (TNBC) is a subtype of that lacks expression estrogen receptor, progesterone and the HER2 but enriched with stem cell–like cells (CSC). CSCs are fraction recognized as source primary malignant tumors also give rise to metastatic recurrence. 5-Hydroxymethylcytosine (5hmC) DNA epigenetic feature derived from 5-methylcytosine by action tet methylcytosine dioxygenase enzymes (e.g., TET1); although TET1 5hmC required maintain embryonic cells, mechanism role...