A5084866518- Prostate Cancer Treatment and Research
- Prostate Cancer Diagnosis and Treatment
- Estrogen and related hormone effects
- Angiogenesis and VEGF in Cancer
- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
- Urologic and reproductive health conditions
- Cytokine Signaling Pathways and Interactions
- Cancer Cells and Metastasis
- Complement system in diseases
- Cell Adhesion Molecules Research
- Single-cell and spatial transcriptomics
- MicroRNA in disease regulation
- Immune Cell Function and Interaction
- Congenital heart defects research
- Blood groups and transfusion
- Cancer, Hypoxia, and Metabolism
- Kruppel-like factors research
- Advanced Breast Cancer Therapies
- Inflammatory Bowel Disease
- Glycosylation and Glycoproteins Research
- Hemoglobinopathies and Related Disorders
- Metabolism, Diabetes, and Cancer
- Clinical Nutrition and Gastroenterology
- Growth Hormone and Insulin-like Growth Factors
Regeneron (United States)
2006-2023
New York University
2000-2006
University of Cape Town
1991-2005
Borough of Manhattan Community College
2005
Kyushu University
2005
Columbia University Irving Medical Center
2001
Kaplan (United States)
2000
Universidade de Santo Amaro
1987
University of South Africa
1987
Stem cells are believed to regulate normal prostatic homeostasis and play a role in the etiology of prostate cancer benign hyperplasia. We show here that proximal region mouse ducts is enriched subpopulation epithelial exhibit three important attributes stem cells: they slow cycling, possess high vitro proliferative potential, can reconstitute highly branched glandular ductal structures collagen gels. propose model which concentrated while transit-amplifying occupy distal ducts. This account...
We previously showed that prostatic stem cells are concentrated in the proximal regions of ducts. now report these can be purified from isolated duct by virtue their high expression cell surface protein antigen 1 (Sca-1). In an vivo prostate reconstitution assay, Sca-1-expressing population region ducts was more effective generating tissue than a comparable Sca-1-depleted (203.0 ± 83.1 mg vs. 11.9 9.2 mg) or remaining (transit-amplifying cells) (31.9 24.1 mg). Almost all proliferative...
We have previously shown that prostatic stem cells are located in the proximal region of mouse ducts. Here, we show this responds differently to transforming growth factor (TGF)-β than distal ductal and under physiological conditions androgens TGF-β crucial overall regulators tissue homeostasis. This conclusion is supported by observations showing high levels signaling present quiescent ducts an androgen-replete animal overexpress Bcl-2, which protects them from apoptosis. Moreover, androgen...
Although many patients with diffuse large B cell lymphoma (DLBCL) may achieve a complete response to frontline chemoimmunotherapy, relapsed/refractory disease typically have poor outcomes. Odronextamab, CD20xCD3 bispecific antibody that provides “signal 1” through the activation of T receptor/CD3 complex, has exhibited early, promising activity for highly refractory DLBCL in phase 1 trials. However, not all responses, and relapse, thus representing high unmet medical need. Here, we...
Prostate carcinoma and benign prostatic hypertrophy may both originate in stem cells, highlighting the importance of characterization these cells. The prostate gland contains a network ducts each which consists proximal (adjacent to urethra), an intermediate, distal region. Here, we report that two populations cells capable regenerating tissue vivo reconstitution assay are present different regions ducts. first population (with considerable growth potential) resides region urethra, survival...
Abstract The Notch ligand delta-like 4 (Dll4) has been identified as a promising target in tumor angiogenesis preclinical studies, and Dll4 inhibitors have recently entered clinical trials for solid tumors, including ovarian cancers. In this study, we report the development of REGN421 (enoticumab), fully human IgG1 monoclonal antibody that binds with sub-nanomolar affinity inhibits signaling. Administering to immunodeficient mice engineered express inhibited growth several xenografts...
Tumour growth requires accompanying expansion of the host vasculature, with tumour progression often correlated vascular density. Vascular endothelial factor (VEGF) is best-characterized inducer angiogenesis. We report that VEGF dynamically regulates expression Delta-like ligand 4 (Dll4), which was previously shown to be absolutely required for normal embryonic development. To define Dll4 function in angiogenesis, we manipulated this pathway murine models using several approaches. Here show...
The Prolactin Receptor (PRLR) is a type 1 cytokine receptor that expressed in subset of breast cancers and may contribute to its pathogenesis. It relatively overexpressed approximately 25% human tumors while at low levels some normal tissues including the mammary gland. We developed an anti-PRLR antibody-drug conjugate (ADC), target PRLR-positive cancer. REGN2878-DM1 comprised fully high-affinity function-blocking IgG1 antibody (REGN2878) conjugated via noncleavable SMCC linker cytotoxic...
Abstract The essential role of the Delta‐like ligand 4 (Dll4)‐Notch signaling pathway in T‐lymphocyte development is well established. It has been shown that specific inactivation Dll4 on thymic stromal cells during early post‐natal leads to a deregulation T‐cell differentiation. However, whether ongoing Dll4‐Notch required for adult thymus unknown. use anti‐Dll4 Abs allowed us confirm and expand previous studies by examining kinetics reversibility blockade mice. We found treatment reduced...
Two prostatic epithelial lines, one of basal origin and luminal origin, were established from the dorsolateral prostates p53 null mice. The cell lines are nontumorigenic when inoculated subcutaneously under renal capsule or intraprostatically in syngeneic line (PE-L-1) expresses cytokeratins 8 18 (PE-B-1) 5 14. cells require serum for growth, whereas grow only serum-free medium. Both presence growth factors optimal culture, with EGF FGF-2 having greatest effect on rate. express androgen...
Crohn’s disease is an inflammatory bowel (IBD) commonly treated through anti-TNF blockade. However, most patients still relapse and inevitably progress. Comprehensive single-cell RNA-sequencing (scRNA-seq) atlases have largely sampled with established treatment-refractory IBD, limiting our understanding of which cell types, subsets, states at diagnosis anticipate severity response to treatment. Here, combining clinical, flow cytometry, histology, scRNA-seq methods, we profile diagnostic...
A prostatic smooth muscle cell line (PSMC1) was established from the dorsolateral prostate of p53 null mice. The is nontumorigenic when inoculated subcutaneously, under renal capsule or intraprostatically in syngeneic These cells express α–smooth actin (α-SMA), indicating their origin, and TGF-β significantly enhances expression α-SMA. both androgen receptor (AR) mRNA protein, respond mitogenically to physiological concentrations androgens. PSMC1 produce significant amounts TGF-β, which...
Abstract Basic fibroblast growth factor (bFGF) is produced by bone marrow stromal cells as well normal and leukemic hematopoietic cells. In this study, we examine the direct effects of bFGF on erythroid differentiation in K562 order to determine whether can promote expression a primitive phenotype. Low levels inhibited evidenced decreased glycophorin A increased c‐kit. also both numbers sizes colonies soft agar assays. The addition TGF‐β these induced which resulted an increase decrease...
Crohn’s disease is an inflammatory bowel (IBD) commonly treated through anti-TNF blockade. However, most patients still relapse and inevitably progress. Comprehensive single-cell RNA-sequencing (scRNA-seq) atlases have largely sampled with established treatment-refractory IBD, limiting our understanding of which cell types, subsets, states at diagnosis anticipate severity response to treatment. Here, combining clinical, flow cytometry, histology, scRNA-seq methods, we profile diagnostic...
Abstract BACKGROUND We have derived a panel of p53‐null prostatic “basal” and “luminal” epithelial cell lines their ras transformed counterparts to study stromal/epithelial interactions the properties tumors arising from cells. METHODS Previously normal murine (PE‐B‐1) (PE‐L‐1) were with N‐Ras. These spontaneously line inoculated subcutaneously or orthotopically into athymic mice, alone in combination smooth muscle cells (SMC). RESULTS All formed subcutaneous tumors. SMC significantly...
Abstract Crohn’s disease is an inflammatory bowel (IBD) commonly treated through anti-TNF blockade. However, most patients still relapse and inevitably progress. Comprehensive single-cell RNA-sequencing (scRNA-seq) atlases have largely sampled with established treatment-refractory IBD, limiting our understanding of which cell types, subsets, states at diagnosis anticipate severity response to treatment. Here, combining clinical, flow cytometry, histology, scRNA-seq methods, we profile...
The interaction of human C-reactive protein (CRP) and serum amyloid P-component (SAP) with isolated rat liver nuclei was studied to identify nuclear ligands for each pentraxin using the iodinatable heterobifunctional thiol-cleavable cross-linking reagent sulphosuccinimidyl-2-(p-azidosalicylamido)-1,3′-dithiopropio nate (SASD). Nuclei (100 micrograms DNA) bound 21 pmol 125I-labelled CRP Ca(2+)-dependently at saturation half-saturation occurring 200 125I-CRP. By contrast, only 2.7 SAP...
One of the major constraints in elucidating mechanisms involved etiology benign prostatic hyperplasia (BPH) is lack suitable model systems that are readily manipulable vitro and vivo. To address this issue, we have used murine cell lines to establish a novel vivo for studying interactions.Luminal, basal, smooth muscle (SM) were inoculated alone or combinations under renal capsule intact castrated male mice, growth composition tissue absence presence doxazosin was determined.Both luminal...
Abstract Breast cancer is a heterogeneous disease comprised of various subtypes based on pathology and molecular profiling. Expression hormone receptors (HR) HER2 biomarkers are important determinants therapy choice, due to the established role these proteins as drivers disease. Prolactin Receptor (PRLR) type 1 cytokine receptor that expressed subset breast cancers may contribute pathogenesis. Functionally, activation PRLR by ligand (PRL) induces dimerization signaling resulting in cell...
Abstract The Notch ligand delta-like 4 (Dll4) has been identified as a promising new target in tumor angiogenesis preclinical studies, and Dll4 inhibitors have recently entered clinical trials for solid tumors, including ovarian cancers. We previously demonstrated that pharmacological blockade of the Dll4-Notch axis results vessel abnormalization associated reduction growth. Using VelocImmune® mice, we fully human IgG1 monoclonal antibody, REGN421 (called enoticumab), which binds with...
<p>Supplementary Figure S1: Correlation of REGN421 serum concentrations and anti-HT1080 tumor activity Supplementary S2: The potent anti-tumor targeting Dll4 in ovarian xenograft models is dependent on blocking stromal S3: antibody REGN1035 treatment induces abnormal vessels cancer S4: expression restricted to the vasculature S5: Notch receptor S6: signaling TOV-112D cells mediated predominantly by Notch1 S7: Combined blockade VEGF reverses liver vascular changes induced alone S8:...