A5006434494- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Advanced Biosensing Techniques and Applications
- Immune cells in cancer
- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Chemokine receptors and signaling
- Cancer Genomics and Diagnostics
- Radiomics and Machine Learning in Medical Imaging
- Glioma Diagnosis and Treatment
- Liver physiology and pathology
- Gene expression and cancer classification
- Bladder and Urothelial Cancer Treatments
- Virus-based gene therapy research
- Nuclear Structure and Function
- RNA Research and Splicing
- Hepatitis B Virus Studies
- Nanoplatforms for cancer theranostics
- Immune Cell Function and Interaction
- Fibroblast Growth Factor Research
- Single-cell and spatial transcriptomics
- Cancer Cells and Metastasis
- Renal cell carcinoma treatment
- Neuroendocrine Tumor Research Advances
Navidea Biopharmaceuticals (United States)
2017-2024
Novartis (United States)
2014-2024
BioPharm (United Kingdom)
2023
Yale University
2008-2018
Vanderbilt University Medical Center
2018
Institut Jules Bordet
2018
California University of Pennsylvania
2018
University of Alabama
2018
Peter MacCallum Cancer Centre
2018
U-M Rogel Cancer Center
2018
Created with both in vitro and vivo data, NetPhorest is an atlas of consensus sequence motifs for 179 kinases 104 phosphorylation-dependent binding domains reveals new insight into signaling.
Abstract Purpose: PD-1/L1 axis–directed therapies produce clinical responses in a subset of patients; therefore, biomarkers response are needed. We hypothesized that quantifying key immunosuppression mechanisms within the tumor microenvironment by multiparameter algorithms would identify strong predictors anti–PD-1 response. Experimental Design: Pretreatment biopsies from 166 patients treated with across 10 academic cancer centers were fluorescently stained multiple markers discovery (n =...
Immunotherapies targeting the PD-1 pathway produce durable responses in many cancers, but tumor-intrinsic factors governing response and resistance are largely unknown. MHC-II expression on tumor cells can predict to anti-PD-1 therapy. We therefore sought determine how by promotes dependency. Using transcriptional profiling of anti-PD-1-treated patients, we identified unique patterns immune activation MHC-II+ tumors. In patients preclinical models, tumors recruited CD4+ T developed...
<h3>Background</h3> Renal medullary carcinoma (RMC) is a rare kidney tumor that occurs in adolescent and young adults, typically association with sickle cell trait. RMC exhibits rapid disease progression, frequent metastases at diagnosis, dismal clinical outcomes. Currently available therapies, including cisplatin-based combination chemotherapy, multi-tyrosine kinase, mTOR inhibitor strategies demonstrate either transient responses or minimal activity. Therefore, further molecular...
Platinum-based chemotherapy is usually curative for patients with testicular germ cell tumors (TGCT), but a subset of experience disease progression and poor clinical outcomes. Here, we tested whether immune profiling TGCT could identify novel prognostic markers therapeutic targets this patient cohort. We obtained primary metastatic samples from one center. performed using multiplexed fluorescence immunohistochemistry (FIHC) T-cell subsets checkpoints, targeted gene expression (Nanostring...
BackgroundApproximately 10% of patients with SCLC develop a paraneoplastic syndrome (PNS). Neurologic PNS are thought to improve prognosis, which we hypothesized is related increased tumor-infiltrating lymphocytes and immune recognition.MethodsWe queried 2,512,042 medical records from single institution identify who have without performed manual, retrospective chart review. We then multiplexed fluorescence immunohistochemistry automated quantitative analysis (AQUA Technology) on tumors...
The RNA binding protein Lin28 and its paralog Lin28B are associated with advanced human malignancies. Blocking the biogenesis of let-7 miRNA, a tumor suppressor, by Lin28/Lin28B has been thought to underlie their roles in cancer. Here we report that mRNA for epidermal growth factor receptor 2 (HER2), HER-family tyrosine kinase known play critical role cell proliferation survival also major therapeutic target breast cancer, is among several targets regulation. We show stimulates HER2...
Quantification of mRNA has historically been done by reverse transcription polymerase chain reaction (RT-PCR). Recently, a robust method detection utilizing in situ hybridization described that is linear and shows high specificity with low background. Here we describe the use AQUA quantitative immunofluorescence (QIF) for measuring using ESR1 (the estrogen receptor alpha gene) breast cancer to determine its predictive value compared Estrogen Receptor α (ER) protein.Messenger RNA ER (ESR1)...
Triple-negative breast cancers (TNBCs) are heterogeneous and aggressive, with high mortality rates. TNBCs frequently respond to chemotherapy, yet many patients develop chemoresistance. The molecular basis roles for tumor cell–stromal crosstalk in establishing chemoresistance complex largely unclear. Here we report studies of paired TNBC patient–derived xenografts (PDXs) established before after the development Interestingly, chemoresistant model acquired a distinct KRASQ61R mutation that...
// Daniel J. O'Shannessy 1 , Elizabeth B. Somers Lakshmi K. Chandrasekaran 2 Nicholas C. Nicolaides Jennifer Bordeaux and Mark D. Gustavson Department of Translational Medicine Diagnostics, Morphotek Inc., Exton, PA HistoRx Inc. (A subsidiary Genoptix Medical Laboratory, Inc.), Carlsbad, CA Correspondence: O'Shannessy, email: Keywords : Endosialin, TEM-1, CRC, tumor microenvironment, prognosis Received April 20, 2014 Accepted June 14, Published 16, Abstract Tumor survival is influenced by...
Abstract Purpose: Neoadjuvant immunotherapy may improve the clinical outcome of regionally advanced operable melanoma and allows for rapid pathologic assessment response. We examined neoadjuvant pembrolizumab high-dose IFNα-2b (HDI) therapy in patients with resectable melanoma. Patients Methods: stage III/IV were treated concurrent 200 mg i.v. every 3 weeks HDI 20 MU/m2/day i.v., 5 days per week 4 weeks, then 10 subcutaneously 2 weeks. Definitive surgery followed, as did adjuvant combination...
Analysis of the interactions low-risk human papillomavirus type 11 (HPV11) L2 with karyopherin beta (Kap beta) nuclear import receptors revealed that interacted Kap 1, 2, and 3 formed a complex alpha 2 1 heterodimer. HPV11 contains two localization signals (NLSs)-in N terminus C terminus-that could mediate its via classical pathway. Each NLS was functional in vivo, deletion both them abolished localization. Both NLSs viral DNA. Thus, can interact several karyopherins DNA may enter nucleus...
Background We sought to determine the predictive value of in situ mRNA measurement compared traditional methods on a cohort trastuzumab-treated metastatic breast cancer patients. Methods A tissue microarray composed 149, classified as HER2-positive, cancers treated with various trastuzumab-containing chemotherapy regimens was constructed. HER2 intracellular domain(ICD), extracellular domain(ECD) and were assessed using AQUA. For protein evaluation, CB11 used measure ICD SP3 ECD receptor. In...
Background HER2/Neu (ErbB-2) overexpression, which occurs in 15–20% of breast cancer cases, is associated with better response to treatment the drug trastuzumab. PhosphoHER2 (pHER2) has been evaluated for prediction Both markers are heterogeneously detected and potentially subject loss as a consequence delayed time fixation. Here, we quantitatively assess both core needle biopsies (CNBs) matched tumor resections concordance between resection HER2 pHER2. Methods A selected retrospective...
Predicting response to ICI therapy among patients with renal cell carcinoma (RCC) has been uniquely challenging. We analyzed patient characteristics and clinical correlates from a retrospective single-site cohort of advanced RCC receiving anti-PD-1/PD-L1 monotherapy (N = 97), as well molecular parameters in subset patients, including multiplexed immunofluorescence (mIF), whole exome sequencing (WES), T receptor (TCR) sequencing, RNA (RNA-seq). Clinical factors such the development...
Abstract Purpose: Deeper understanding of the intricacies between tumor microenvironments and immune cell infiltrates is critical for creation next generation therapies. However, current immunohistochemistry protocols in clinical practice are restricted to one six markers (cell types) rely on multiple rounds antigen retrieval sequential staining over two days. This workflow has high risk tissue signal loss. Hence, we explored utility a single step using 15 distinct antibodies conjugated...
180 Background: Anti-PD-1 therapy is effective in many cancers, but tumor-intrinsic factors governing response and resistance are largely unknown. MHC-II (HLA-DR) expression on tumor cells can predict to anti-PD-1. Thus, we sought determine the molecular features of MHC-II+ tumors evolution anti-PD-1 response. Methods: We performed RNA-seq 58 treated melanoma lung tumors, including a subset matched specimens prior treatment at acquired resistance. immunohistochemistry (IHC) for immunologic...
12058 Background: Although patients with high tumor programmed death ligand-1(PD-L1) expression benefit from PD-1/PD-L1 axis inhibitors, many studies have highlighted that a fraction of respond to these agents despite lacking detectable PD-L1 expression. Heterogeneity within the has been postulated be contributing limited performance as predictive biomarker. We evaluated heterogeneity by comparing percentage positive cells measure proportion scores (TPS) using fluorescence...