A5044261990- Colorectal Cancer Treatments and Studies
- Radiomics and Machine Learning in Medical Imaging
- Genetic factors in colorectal cancer
- Cancer Treatment and Pharmacology
- Cancer Immunotherapy and Biomarkers
- Colorectal Cancer Screening and Detection
- Microscopic Colitis
- AI in cancer detection
- Colorectal Cancer Surgical Treatments
- Medical Imaging Techniques and Applications
- Cancer Genomics and Diagnostics
- Glycosylation and Glycoproteins Research
- Lung Cancer Treatments and Mutations
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- Esophageal Cancer Research and Treatment
- Microtubule and mitosis dynamics
- HER2/EGFR in Cancer Research
- Genomics and Phylogenetic Studies
- Caveolin-1 and cellular processes
- Cancer, Lipids, and Metabolism
- Developmental Biology and Gene Regulation
- Wnt/β-catenin signaling in development and cancer
- Liver Disease Diagnosis and Treatment
- Gastric Cancer Management and Outcomes
Roche (United States)
2021-2025
HTG Molecular Diagnostics (United States)
2024
St James's University Hospital
2023
Wellcome Trust
2023
Ventana Research Corporation (United States)
2013-2021
City Of Hope National Medical Center
2019
The University of Texas MD Anderson Cancer Center
2019
City of Hope
2019
Mayo Clinic in Arizona
2005-2010
Translational Genomics Research Institute
2007
HER2 amplification has been implicated in resistance to therapy with anti-epidermal growth factor receptor antibodies (anti-EGFRabs) metastatic colorectal cancer (mCRC). The purpose of the study was validate predictive impact mCRC.We analyzed patients RAS/BRAF wild-type mCRC across two distinct cohorts. In cohort 1 (n = 98), tested tumor tissue using dual situ hybridization (HER2 amplification: HER2/CEP17 ratio, 2.0 or greater). Cohort 2 70) included 16 and 54 nonamplified controls...
Background Lung cancer is the second most common in incidence and leading cause of deaths worldwide.Meanwhile, lung screening with low-dose CT can reduce mortality.The UK National Screening Committee recommended targeted on Sept 29, 2022, asked for more modelling work to be done help refine recommendation.This study aims develop validate a risk prediction model-the CanPredict (lung) model-for compare model performance against seven other models.Methods For this retrospective,...
HOX, PBX, and MEIS transcription factors bind DNA through a homeodomain. PBX proteins cooperatively as heterodimers with family members also HOX from paralog groups 1 to 10. ABD-B class of 9 Here, we examine aspects dimeric higher-order interactions between these three homeodomain classes. The most significant results can be summarized follows. (i) Most N terminal the is required for efficient cooperative binding HOXD4 HOXD9. (ii) form complexes on heterodimeric site. (iii) Although does not...
Abstract MUC1 is a heterodimeric transmembrane glycoprotein that overexpressed and aberrantly glycosylated in ductal adenocarcinomas. Differential phosphorylation of the cytoplasmic tail (MUC1CT) has been associated with signaling events influence proliferation metastasis cancer cells. We identified novel tyrosine site (HGRYVPP) MUC1CT by mass spectrometric analysis from human pancreatic adenocarcinoma cell lines. Analyses vitro vivo showed platelet-derived growth factor receptor β (PDGFRβ)...
Abstract Purpose: Colorectal cancers with deficient DNA mismatch repair (dMMR) are presumed to uniformly have dense lymphocytic infiltration that underlies their favorable prognosis and is critical responsiveness immunotherapy, as compared MMR-proficient (pMMR) tumors. We examined T-cell densities potential heterogeneity in a large cohort of dMMR Experimental Design: CD3+ CD8+ were quantified at the invasive margin (IM) tumor core (CT) 561 stage III colon (dMMR, n = 278; pMMR, 283) from...
3517 Background: HER2 amplification (HERamp), seen in 5% of KRAS wildtype (WT) metastatic colorectal cancers (mCRC), is associated with resistance to anti-epidermal growth factor receptor antibodies (antiEGFRabs). The purpose this study was validate the predictive impact HERamp mCRC. Methods: We performed systematic analyses RAS and BRAF WT mCRC patients (pts) across 2 distinct cohorts. tested cohort 1 (N = 97) using immunohistochemistry dual in-situ hybridization (HERamp: HER2/CEP17 ≥ 2.2)....
MUC1, a transmembrane mucin, is key modulator of several signaling pathways that affect oncogenesis, motility, and cell morphology. The interaction MUC1 cytoplasmic tail (MUC1CT) with signal transducers its nuclear translocation subsequent biological responses are believed to be regulated by phosphorylation status, but the precise mechanisms which this occurs remain poorly defined. We detected novel association between Met receptor tyrosine kinase MUC1CT. catalyzed at YHPM in Stimulation...
BACKGROUND A point mutation (V600E) in the BRAF oncogene is a prognostic biomarker and may predict for nonresponse to anti‐EGFR antibody therapy patients with colorectal carcinoma. V600E mutations are frequently detected tumors microsatellite instability indicate sporadic origin. We used mutation‐specific examine mutant protein expression its concordance data. METHODS Primary stage III colon carcinomas were analyzed exon 15, 50 carriers 25 wild‐type selected analysis of proteins by...
The B-type Raf kinase (BRAF) V600E mutation is a well-established biomarker for poor prognosis in metastatic colorectal cancer (mCRC) and highly attractive drug target. A barrier to the development of new therapies targeting BRAF mCRC low prevalence mutations (approximately 10 %) current need access sequencing-based technologies which are not routinely available outside large centres. Availability standardised immunohistochemistry (IHC) test, more suited routine pathology practice, would...
Abstract Deep learning may detect biologically important signals embedded in tumor morphologic features that confer distinct prognoses. Tumor were quantified to enhance patient risk stratification within DNA mismatch repair (MMR) groups using deep learning. Using a quantitative segmentation algorithm (QuantCRC) identifies 15 features, we analyzed 402 resected stage III colon carcinomas [191 deficient (d)-MMR; 189 proficient (p)-MMR] from participants phase trial of FOLFOX-based adjuvant...
PURPOSE High densities of tumor infiltrating CD3 and CD8 T-cells are associated with superior prognosis in colorectal cancer (CRC). Their value as predictors benefit from adjuvant chemotherapy is uncertain. PATIENTS AND METHODS Tumor tissue 868 patients the QUASAR trial (adjuvant fluorouracil/folinic acid v observation stage II/III CRC) was analyzed by immunohistochemistry. Pathologists, assisted artificial intelligence, calculated cell (cells/mm 2 ) core (CT) invasive margin (IM)....
Abstract Purpose. Digital proteomic profiling was performed to identify spatial context in relationship patient response and survival after anti-PD-1 therapy metastatic colorectal cancer (CRC). Experimental Design. Primary CRCs with deficient mismatch repair (d-MMR) from patients treated antibodies were analyzed (N=30) using Spatial Profiling (GeoMx® nCounter). At the invasive margin, 71 proteins profiled 10 regions of interest /slide that segmented into 3 compartments labeled...
Abstract Much of the ability MUC1 oncoprotein to foster tumorigenesis and tumor progression likely originates from interaction its cytoplasmic tail with proteins involved in oncogenic signaling. Many these interactions are regulated by phosphorylation, as contains seven highly conserved tyrosines several serine/threonine phosphorylation sites. We have developed a cell line–based model system study effects tyrosine on signaling, particular emphasis gene transcription. COS-7 cells, which lack...
The aim of this study was to analyse the immunophenotypic and molecular features a large series follicular lymphomas, focusing in particular on atypical cases that fail express CD10 and/or bcl-2. Such present diagnostic pitfalls, especially with regard differential diagnosis from hyperplasia marginal zone B-cell lymphoma. Therefore, we also included an immunohistochemical evaluation stathmin, which is strongly expressed by germinal centre B cells, as putative new marker for particularly...
Prognostic markers that identify patients with stage II colon cancers who are at the risk of recurrence essential to personalize therapy. We evaluated potential GIV/Girdin as a predictor in such patients.Expression full-length GIV was by IHC using newly developed mAb together mismatch repair (MMR)-specific antibody panel three cancer patient cohorts, is, training (n = 192), test 317), and validation 181) cohort, clinical follow-up data. Recurrence stratification models were established...
Abstract Purpose: Targeting the programmed cell death protein 1 (PD-1)/programmed ligand (PD-L1) interaction has led to durable responses in fewer than half of patients with mismatch repair–deficient (MMR-d) advanced colorectal cancers. Immune contexture, including spatial distribution immune cells tumor microenvironment (TME), may predict immunotherapy outcome. Experimental Design: contexture and distribution, cell-to-cell distance measurements, were analyzed by multiplex immunofluorescence...
Hox genes encode transcription factors that are major determinants of embryonic patterning. Recently, we and others have shown specific recognition target sites in DNA is partly achieved through cooperative interaction with the extradenticle/pre-B-cell transformation-related gene (EXD/PBX) family homeodomain-containing proteins. This mediated by YPWM motif present N-terminal to homeodomain HOX In study, use peptides confirm importance this for mediating HOX/PBX interactions. We also used a...
In the era of immune checkpoint inhibitors, understanding metastatic microenvironment proficient mismatch repair/microsatellite stable (pMMR/MSS) colorectal cancer (CRC) is paramount importance to both prognostication and development more effective novel therapies. this study, primary paired metastasis tissue samples were collected from patients with resectable CRC treated adjuvant FOLFOX or peri-operative chemotherapy in MIROX phase III prospective study. total, 74 tissues stained for CD3,...
The Wnt-beta-catenin pathway plays a central role in colorectal tumorigenesis. Frizzled-related protein (FRZB, also termed secreted frizzled-related 3, sFRP3) antagonizes the signaling of wingless (Wnt) ligands through frizzled membrane-bound receptors, resulting beta-catenin destabilization thereby suppressing expression target genes. Recently, FRZB Gly324 variant has been shown to have an attenuated ability antagonize Wnt and be associated with increased osteoarthritis risk. Here, we...
High tumor mRNA levels of the EGFR ligands amphiregulin (AREG) and epiregulin (EREG) are associated with anti-EGFR agent response in metastatic colorectal cancer (mCRC). However, ligand RNA assays have not been adopted into routine practice due to issues analytic precision practicality. We investigated whether AREG/EREG IHC could predict benefit from panitumumab.Artificial intelligence algorithms were developed assess 274 patients PICCOLO trial irinotecan or without panitumumab (Ir vs....