A5066141980- Renal cell carcinoma treatment
- Cancer Immunotherapy and Biomarkers
- Ferroptosis and cancer prognosis
- Immune cells in cancer
- CNS Lymphoma Diagnosis and Treatment
- Bladder and Urothelial Cancer Treatments
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Colorectal Cancer Treatments and Studies
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Cytokine Signaling Pathways and Interactions
- Genetic factors in colorectal cancer
- Melanoma and MAPK Pathways
- Cancer-related gene regulation
- Hemoglobinopathies and Related Disorders
- Cancer Research and Treatments
- Blood groups and transfusion
- Iron Metabolism and Disorders
- Trace Elements in Health
- RNA regulation and disease
- Colorectal Cancer Screening and Detection
- Lung Cancer Treatments and Mutations
- Genetic and Kidney Cyst Diseases
- Renal and related cancers
- Atherosclerosis and Cardiovascular Diseases
Novartis (United States)
2019-2024
Precision for Medicine (United States)
2019-2024
Novartis (Switzerland)
2023
Predictive Science (United States)
2011-2013
Exact Sciences (United States)
2008
University of Pennsylvania
2003-2006
Cancer Research Institute of the Slovak Academy of Sciences
2006
Cancer Research Institute
2004-2006
UPMC Hillman Cancer Center
2004
Tufts University
2003-2004
Human acute T-cell lymphoblastic leukemias and lymphomas (T-ALL) are commonly associated with gain-of-function mutations in Notch1 that contribute to T-ALL induction maintenance. Starting from an expression-profiling screen, we identified c-myc as a direct target of Notch-dependent cell lines, which Notch accounts for the majority expression. In functional assays, inhibitors interfere progrowth effects activated Notch1, enforced expression rescues multiple Notch1-dependent lines withdrawal....
Journal Article Analysis of the genomic sequence for autosomal dominant polycystic kidney disease (PKD1) gene predicts presence a leucine-rich repeat: The AMERICAN PKD1 Consortium (APKD1 Consortium) Get access Timothy C. Burn, Burn Search other works by this author on: Oxford Academic PubMed Google Scholar D. Connors, Connors William R. Dackowski, Dackowski Linda Petry, Petry Terence J. van Raay, Raay John M. Millholland, Millholland Marc Venet, Venet Glenn Miller, Miller Ramond Hakim, Hakim...
Genetic inactivation of Notch signaling in CD4−CD8− double-negative (DN) thymocytes was previously shown to impair T cell receptor (TCR) gene rearrangement and cause a partial block CD4+CD8+ double-positive (DP) thymocyte development mice. In contrast, vitro cultures suggested that absolutely required for the generation DP independent pre-TCR expression activity. To resolve respective role pre-TCR, we inhibited Notch-mediated transcriptional activation vivo with green fluorescent...
As a noninvasive colorectal cancer (CRC) screening test, multi-marker first generation stool DNA (sDNA V 1.0) test is superior to guaiac-based fecal occult blood tests. An improved sDNA assay (version 2), utilizing only two markers, hypermethylated vimentin gene (hV) and site integrity (DY), demonstrated in training set (phase 1a) an even higher sensitivity (88%) for CRC with specificity of 82%.To validate independent patients 1b) the version 2 CRC.Forty-two 241 subjects normal colonoscopy...
Abstract High levels of IL1β can result in chronic inflammation, which turn promote tumor growth and metastasis. Inhibition could therefore be a promising therapeutic option the treatment cancer. Here, effects blockade induced by mAbs canakinumab gevokizumab were evaluated alone or combination with docetaxel, anti–programmed cell death protein 1 (anti–PD-1), anti-VEGFα, anti-TGFβ syngeneic humanized mouse models cancers different origin. Canakinumab did not show notable efficacy as...
Abstract Purpose: The influence of the transcriptional and immunologic context mutations on therapeutic outcomes with targeted therapy in cancer has not been well defined. BRAF V600E–mutant (BM) colorectal comprises two main subtypes, BM1 BM2. We sought to determine impact BM subtype, as distinct biological features those response BRAF/MEK/EGFR inhibition patients cancer. Patients Methods: Paired fresh tumor biopsies were acquired at baseline day 15 treatment from all consenting enrolled a...
Abstract It is poorly understood how the tumor immune microenvironment influences disease recurrence in localized clear-cell renal cell carcinoma (ccRCC). Here we performed whole-transcriptomic profiling of 236 tumors from patients assigned to placebo-only arm a randomized, adjuvant clinical trial for high-risk ccRCC. Unbiased pathway analysis identified myeloid-derived IL6 as key mediator. Furthermore, novel myeloid gene signature strongly correlated with and overall survival on uni-...
Previously we reported that ferritin in corneal epithelial (CE) cells is a nuclear protein protects DNA from UV damage. Since normally cytoplasmic, CE cells, mechanism must exist effects its localization. We have now determined this involves transport molecule termed ferritoid. Ferritoid specific for and developmentally regulated. Structurally, ferritoid contains multiple domains, including functional SV40-type localization signal ferritin-like region of ∼50% similarity to itself. This...
A 700-kb region of DNA in human chromosome 16p13.3 has been shown to contain the polycystic kidney disease 1 (PKD1) and tuberous sclerosis type 2 (TSC2) genes. An estimated 20 genes are present this 16. We have initiated studies identify transcribed sequences using a bacteriophage P1 contig containing 700 kb surrounding PKD1 TSC2 isolated 96 unique exon traps from interval, with 23 trapped exons five known be region. Thirty mapped additional transcription units based on data base homologies,...
Abstract Introduction: Inflammation is a hallmark of cancer wherein diverse immune cells exert either pro- or antitumor properties and affect therapeutic resistance (Ritter B et al, JEM 2019). High concentrations tumor-promoting inflammatory cytokines such as IL-1β (Litmanovich A Oncol Ther 2018) IL-6 (Altundag O J Clin 2005) correlate with advanced malignancies are associated reduced survival. recent phase III clinical trial (CANTOS) demonstrated that canakinumab, selective inhibitor, could...
Abstract Introduction: TPI is a hallmark of cancer and plays pivotal role in tumor initiation, development, progression, invasiveness. High levels tumor-promoting inflammatory cytokines e.g. IL-1β IL-6 are associated with advanced malignancies reduced survival. Selective inhibitors like canakinumab (CAN) gevokizumab (GEV) aim to target within the microenvironment (TME) by reducing tumor-associated immune suppression. In phase III CANTOS study, CAN significantly lung (LC) incidences LC...
<div>Abstract<p>High levels of IL-1β can result in chronic inflammation, which turn promote tumor growth and metastasis. Inhibition could therefore be a promising therapeutic option the treatment cancer. Here, effects blockade induced by monoclonal antibodies canakinumab gevokizumab were evaluated alone or combination with docetaxel, anti-PD-1, anti-VEGFα anti-TGFβ syngeneic humanized mouse models cancers different origin. Canakinumab did not show notable efficacy as single-agent...
Continuous vaso-occlusive and inflammatory processes cause extensive end-organ damage in adults with sickle cell disease (SCD), there is little evidence that longterm hydroxyurea therapy prevents this. In initial trials, P-selectin blockade crizanlizumab reduced SCD crisis frequency, interleukin (IL)-1β inhibition patients, using canakinumab, lowered markers. We used murine models to examine the effects of acute chronic Pselectin IL-1β on events, their profile organ health. Both approaches...
59 Background: FGFR3 mutations have been identified in ~60-70% of low-stage, non-invasive tumors. Our group and others developed assays to detect the urine bladder cancer patients. However, urine-based limited by technical ability rare events a dilute medium where there is high background normal DNA. In these assays, are generally found ~30% samples, which < 50% concordance with expected detection tissue. We now an ultra-deep amplicon sequencing technique that increases mutation ~67%,...
Abstract Background: We have recently reported the development of a Multi-Analyte Diagnostic Readout (MADR) non-invasive assay using urinary Matrix Metalloproteinases (MMPs) and FGFR3 as triage monitors in high-risk bladder cancer populations. This concept combines marker performance characteristics protein DNA biomarkers into one for optimal performance. Eight common mutations 3 exons been associated with cancer. Analysis mutational status each single mutation required 8 amplification...
Abstract Methylation of the Twist1 gene has been linked to various cancers, including bladder cancer. We are developing a non-invasive diagnostic assay utilizing urinary protein and DNA biomarkers, Twist1, as triage monitors in high-risk cancer populations. Since final clinical performance is dependent on optimal technical each individual marker, we incorporated use chimeric PCR primers establish conditions for all markers that would greatly simplify process optimizing performance....
Abstract Introduction The presence of blood in the urine (hematuria) is one hallmark symptoms bladder cancer. Thus, current best practice policy suggests that patients with hematuria undergo cystoscopic examination. However, can be present healthy individuals as well various non-life threatening conditions such a majority (∼95%) who are screened by cystoscopy do not have In addition, recent studies found referred on to specialist for further invasive tests, despite guidelines. This...
Abstract Background: We have recently described an ultra-deep amplicon sequencing method for detection of FGFR3 mutations in urine that closely matches the frequency found bladder cancer tissue. While are present a large fraction non-invasive tumors, these rarely detected invasive tumors. To complement our existing deep assay, we developed assay TP53. Mutations TP53 commonly advanced cancer, and show little overlap with mutations. Here, demonstrate tissue using Next-Gen platform. Methods:...