A5011734599- Advanced Breast Cancer Therapies
- Cancer-related Molecular Pathways
- Protease and Inhibitor Mechanisms
- Nanoplatforms for cancer theranostics
- PARP inhibition in cancer therapy
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- Cancer, Lipids, and Metabolism
- Microtubule and mitosis dynamics
- Pulmonary Hypertension Research and Treatments
- BRCA gene mutations in cancer
- Biomarkers in Disease Mechanisms
- Ubiquitin and proteasome pathways
- Ocular Oncology and Treatments
- Nuclear Receptors and Signaling
- HER2/EGFR in Cancer Research
- Breast Cancer Treatment Studies
- Gene expression and cancer classification
- Radiomics and Machine Learning in Medical Imaging
- Cancer Mechanisms and Therapy
- S100 Proteins and Annexins
- Monoclonal and Polyclonal Antibodies Research
- Genetics, Bioinformatics, and Biomedical Research
- DNA Repair Mechanisms
- ATP Synthase and ATPases Research
University of Rochester Medical Center
2022-2024
The University of Texas MD Anderson Cancer Center
2015-2024
Brigham and Women's Hospital
2024
Saint Barnabas Medical Center
2022
University of Arkansas for Medical Sciences
2022
New York University
2017-2018
Radiation Oncology Associates
2012-2015
Amasya Üniversitesi
2010-2012
Universität Hamburg
2003
University Medical Center Hamburg-Eppendorf
2003
Abstract Deregulation of the cell cycle machinery is a hallmark cancer. While CDK4/6 inhibitors are FDA approved (palbociclib) for treating advanced estrogen receptor-positive breast cancer, two major clinical challenges remain: (i) adverse events leading to therapy discontinuation and (ii) lack reliable biomarkers. Here we report that cancer cells activate autophagy in response palbociclib, combination induces irreversible growth inhibition senescence vitro, diminishes line patient-derived...
Abstract PARP inhibitors (PARPi) benefit only a fraction of breast cancer patients. Several those patients exhibit intrinsic/acquired resistance mechanisms that limit efficacy PARPi monotherapy. Here we show how the in triple-negative cancers (TNBC) can be expanded by targeting MYC-induced oncogenic addiction. In BRCA-mutant/sporadic TNBC patients, amplification MYC gene is correlated with increased expression homologous DNA recombination enzyme RAD51 and tumors overexpressing both genes are...
Abstract Purpose: Poor prognosis in triple-negative breast cancer (TNBC) is due to an aggressive phenotype and lack of biomarker-driven targeted therapies. Overexpression cyclin E phosphorylated-CDK2 are correlated with poor survival patients TNBC, the absence CDK2 desensitizes cells inhibition Wee1 kinase, a key cell-cycle regulator. We hypothesize that expression can predict response therapies, which include kinase inhibitor, AZD1775. Experimental Design: Mono- combination therapies...
We assessed the interobserver and interantibody reproducibility of HER2 immunohistochemical scoring in an enriched HER2-low-expressing breast cancer cohort.A total 114 specimens were stained by HercepTest (Agilent Dako) PATHWAY anti-HER2 (4B5) (Ventana) antibody assays scored 6 pathologists independently using current guidelines. Level agreement was evaluated Cohen κ analysis.Although rate for both antibodies achieved substantial agreement, average significantly higher than that 4B5 clone...
Paget's disease of the breast is a rare type cancer nipple-areola complex and that often associated with an underlying in situ or invasive carcinoma. This article provides overview we review main clinicopathological therapeutic features mammary disease.
Cyclin E is altered in nearly a third of invasive breast cancers where it powerful independent predictor survival women with stage I-III disease. Full-length cyclin posttranslationally cleaved into low molecular weight (LMW-E) isoforms, which are tumor-specific and accumulate the cytoplasm because they lack nuclear localization sequence. We hypothesized that aberrant cytosolic LMW-E isoforms alters target binding activation ultimately contributing to LMW-E-induced tumorigenicity. To address...
Purpose: Low molecular weight cyclin E (LMW-E) detected by Western blot analysis predicts for reduced breast cancer survival; however, it is impractical clinical use. LMW-E lacks a nuclear localization signal that leads to accumulation in the cytoplasm can be IHC. We tested hypothesis cytoplasmic staining of used as predictor poor outcome different subtypes using patient cohorts with distinct and pathologic features.Experimental Design: evaluated subcellular specimens from 2,494 patients 4...
// Angela Alexander 1, 7, * , Cansu Karakas 1 Xian Chen Jason P.W. Carey Min Yi 2 Melissa Bondy 3 Patricia Thompson 4 Kwok Leung Cheung 5 Ian O. Ellis Yun Gong 6 Savitri Krishnamurthy 6, 7 Ricardo H. Alvarez 8 Naoto T. Ueno Kelly K. Hunt Khandan Keyomarsi Department of Experimental Radiation Oncology, The University Texas MD Anderson Cancer Center, Houston, Texas, USA Surgical Pediatrics, Baylor College Medicine, Pathology, Stony Brook School Brook, New York, Nottingham, UK Morgan Welch...
Abstract Objectives Actionable, solid tumor activating neurotrophic receptor tyrosine kinase ( NTRK ) fusions are best detected via nucleic acid-based assays, while Pan-TRK immunohistochemistry (IHC) serves as a reasonable screening modality. We describe practical and cost-effective approach to validate pan-TRK discuss challenges that may be encountered. Methods Clone EPR17341 was validated in accordance with the 2014 consensus statements set forth by College of American Pathologists....
Purpose: Preoperative aromatase inhibitor (AI) therapy has demonstrated efficacy in hormone receptor (HR)-positive postmenopausal breast cancer. However, many patients have disease that is either intrinsically resistant to AIs or responds initially but develops resistance after prolonged exposure. We shown with tumors expressing the deregulated forms of cyclin E [low molecular weight (LMW-E)] poor overall survival. Herein, we hypothesize LMW-E expression can identify HR-positive are...
The identification of biomarker-driven targeted therapies for patients with triple negative breast cancer (TNBC) remains a major clinical challenge, due to lack specific targets. Here, we show that cyclin E, regulator G1 S transition, is deregulated in TNBC and associated mutations DNA repair genes (e.g., BRCA1/2). Breast cancers high levels E not only have higher prevalence BRCA1/2 mutations, but also are the worst outcomes. Using several vitro vivo model systems, TNBCs harbor either or...
Abstract Introduction Elafin is an endogenous serine protease inhibitor. The majority of breast cancer cell lines lack elafin expression compared to human mammary epithelial cells. In this study, we hypothesized that downregulated during and ovarian tumorigenesis. Methods We examined by immunohistochemistry (IHC) in specimens normal tissue (n = 24), ductal carcinoma situ (DCIS) 54), invasive 793). IHC analysis was also performed fallopian tube 20), cystadenomas 9), borderline tumors 21),...
Abstract Metastatic disease remains the leading cause of death due to cancer, yet mechanism(s) metastasis and its timely detection remain be elucidated. Neutrophil elastase (NE), a serine protease secreted by neutrophils, is crucial mediator chronic inflammation tumor progression. In this study, we used PyMT model (NE+/+ NE−/−) breast cancer interrogate tumor-intrinsic -extrinsic mechanisms which NE can promote metastasis. Our results showed that genetic ablation significantly reduced lung...
The HER-2/neu protein (p185) has become a promising target for antibody therapy in breast cancer. We tested the feasibility of quantitative approach testing based on analysis tumor tissue extracts by an enzyme-linked immunosorbent assay (ELISA).Tumor primary human cancers (n=124) were prepared using triton-based buffer. concentration was quantified ELISA. Paraffin-embedded sections same tumors analyzed immunohistochemical staining applying monoclonal TAB 250 and chromogenic situ...
Purpose The HER-2/neu protein (p185) has become a promising target for antibody therapy in breast cancer. We tested the feasibility of quantitative approach testing based on analysis tumor tissue extracts by an enzyme-linked immunosorbent assay (ELISA). Experimental design Tumor primary human cancers (n=124) were prepared using triton-based buffer. concentration was quantified ELISA. Paraffin-embedded sections same tumors analyzed immunohistochemical staining applying monoclonal TAB 250 and...
Background/aim: To identify the role of gene products associated with apoptosis and cell cycle in pathogenesis thyroid follicular neoplasm. Materials methods: Thirty adenomas (FAs), 16 carcinomas (FCs), 20 adenomatous nodules (ANs) were investigated immunohistochemical staining p16, p21, p27, p53, Bcl-2, Bax, Bcl-xL, cyclin D1 via a tissue microarray method. Results: Bcl-2 showed significant difference between benign groups (AN FA) malignant group (FC). Bax was significantly higher FC group....
Abstract Cyclin E is a regulatory subunit of CDK2 that mediates S phase entry and progression. The cleavage full-length cyclin (FL-cycE) to low–molecular weight isoforms (LMW-E) dramatically alters substrate specificity, promoting G1–S cell cycle transition accelerating mitotic exit. Approximately 70% triple-negative breast cancers (TNBC) express LMW-E, which correlates with poor prognosis. PKMYT1 also plays an important role in mitosis by inhibiting CDK1 block premature entry, suggesting it...
Background: Pathologic complete response (pCR) has been shown to be associated with favorable outcomes in breast cancer. Predictors of pCR could useful guiding treatment decisions regarding neoadjuvant therapy. The objective this study was evaluate cyclin E as a predictor chemotherapy Methods: Patients (n = 285) stage II–III cancer were enrolled prospective and received anthracyclines, taxanes, or combination the two. Pretreatment biopsies from 190 patients surgical specimens following 192...