A5091688844- Cancer Mechanisms and Therapy
- Liver physiology and pathology
- Immune cells in cancer
- PI3K/AKT/mTOR signaling in cancer
- Extracellular vesicles in disease
- Melanoma and MAPK Pathways
- Histone Deacetylase Inhibitors Research
- Cancer, Hypoxia, and Metabolism
- Fibroblast Growth Factor Research
- Synthesis and biological activity
- MicroRNA in disease regulation
- Ferroptosis and cancer prognosis
- RNA modifications and cancer
- Lung Cancer Treatments and Mutations
- Mechanisms of cancer metastasis
- Gastric Cancer Management and Outcomes
- Proteoglycans and glycosaminoglycans research
- Cancer Research and Treatments
- Cancer, Lipids, and Metabolism
- Marine Sponges and Natural Products
- Cancer Cells and Metastasis
- Cancer Genomics and Diagnostics
- Piperaceae Chemical and Biological Studies
- Cancer-related Molecular Pathways
- Molecular Biology Techniques and Applications
Harvard University
2020-2025
Massachusetts General Hospital
2020-2025
Broad Institute
2021-2025
Center for Cancer Research
2009-2025
Massachusetts Institute of Technology
2025
University of Chicago
2005-2021
National Cancer Institute
2009-2018
National Institutes of Health
2009-2015
Science Applications International Corporation (United States)
2012
Target (United States)
2011
Purpose The receptors for hepatocyte and vascular endothelial cell growth factors (MET VEGFR2, respectively) are critical oncogenic mediators in gastric adenocarcinoma. purpose is to examine the safety efficacy of foretinib, an oral multikinase inhibitor targeting MET, RON, AXL, TIE-2, VEGFR2 receptors, treatment metastatic Patients Methods Foretinib tolerability, objective response rate (ORR) were evaluated patients using intermittent (240 mg/day, 5 days every 2 weeks) or daily (80 mg/day)...
Significance Isolation of sufficient numbers circulating tumor cells (CTCs) in cancer patients could provide an alternative to invasive biopsies, providing multianalyte cell-based biomarkers that are not available from current plasma DNA sequencing. Given the average prevalence at one CTC per billion blood cells, very large volumes must be screened enough CTCs for reliable clinical applications. By creating ultrahigh-throughput magnetic sorter, we demonstrate efficient removal leukocytes...
Abstract Triple-negative breast cancer (TNBC) patients have the highest risk of recurrence and metastasis. Because they cannot be treated with targeted therapies, many do not respond to chemotherapy, represent a clinically underserved group. TNBC is characterized by reduced expression metastasis suppressors such as Raf kinase inhibitory protein (RKIP), which inhibits tumor invasiveness. Mechanisms alter cells are well characterized; however, their ability regulate microenvironment importance...
Measuring virus in biofluids is complicated by confounding biomolecules coisolated with viral nucleic acids. To address this, we developed an affinity-based microfluidic device for specific capture of intact severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our approach used engineered angiotensin-converting enzyme to from plasma and other complex biofluids. leverages a staggered herringbone pattern, nanoparticle surface coating, processing conditions achieve detection as few 3...
Purpose: To understand how tumor cells alter macrophage biology once they are recruited to triple-negative breast cancer (TNBC) tumors by CCL5. Method: Mouse bone marrow derived (BMDMs) were isolated and treated with recombinant CCL5 protein alone, cell conditioned media, or extracellular vesicles (EVs). Media from these EV-educated macrophages (TEMs) was then used determine affect TNBC invasion. the mechanism, we assayed cytokine secretion impact Tumor expression varied in its role...
Aberrant expression of viral-like repeat elements is a common feature epithelial cancers, and the substantial diversity species provides distinct view cancer transcriptome. Repeatome profiling across ovarian, pancreatic, colorectal cell lines identifies clustering independent tissue origin that seen with coding gene analysis. Deeper analysis ovarian demonstrated human satellite II (HSATII) was highly associated epithelial-mesenchymal transition (EMT) anticorrelated IFN-response genes...
A new trimethoxycinnamoyl-2-pyrrolinone alkaloid, langkamide (1), along with the known compounds piplartine (2) and 3,4,5-trimethoxycinnamic acid (3) were isolated from roots stems of shrub Piper sarmentosum ROXB. The structures established by spectroscopic analyses comparison their spectral data values reported in literature. tested for ability to modulate hypoxia inducible factor-2 (HIF-2) transcription activity all three showed HIF-2 inhibitory EC50 14.0, 4.8, 60.6 μM, respectively, 1, 2, 3.
Abstract Extracellular vesicles (EVs) are small, lipid‐bilayer‐bound particles released by cells that can contain important bioactive molecules, including lipids, RNAs, and proteins. Once in the extracellular environment, EVs act as messengers locally well to distant tissues coordinate tissue homeostasis systemic responses. There is a growing interest not only understanding physiology of signaling but also leveraging them minimally invasive diagnostic prognostic biomarkers (e.g., they be...
Under normal conditions, hepatocyte growth factor (HGF)-induced activation of its cell surface receptor, the Met tyrosine kinase (TK), is tightly regulated by paracrine ligand delivery, at target surface, and activated receptor internalization degradation. Despite these controls, HGF/Met signaling contributes to oncogenesis tumor progression in several cancers promotes aggressive cellular invasiveness that strongly linked metastasis. The prevalence pathway human malignancies has driven rapid...
Renal or kidney cancer accounts for about 3% of all cases reported each year in the U.S. Molecular signatures that define cancer, such as loss functional VHL, are found both sporadic and familial cancer. In clear cell renal transcription factor HIF-2α has been shown to have a distinct role tumorigenesis. Our laboratories developed cell-based screen identify modulators HIF-2α. Screening NCI's Natural Product Extract Repository resulted identification 10 sponge extracts, from which 12...
Abstract The surrounding microenvironment has been implicated in the progression of breast tumors to metastasis. However, degree which metastatic locally reprogram stromal cells as they disrupt tissue boundaries is not well understood. We used species-specific RNA sequencing a mouse xenograft model determine how metastasis suppressor RKIP influences transcription panel paired tumor and stroma tissues. find that gene expression pervasively correlated with local both xenografts human patients....
Extracellular vesicles (EVs) have emerged as promising candidates in biomarker discovery and diagnostics. Protected by the lipid bilayer, molecular content of EVs diverse biofluids are protected from RNases proteases surrounding environment that may rapidly degrade targets interests. Nonetheless, cryopreservation EV-containing samples to -80°C expose bilayer physical biological stressors which result cryoinjury contribute changes EV yield, function, or cargo. In present work, we...
Abstract Microfluidic devices have been used for decades to isolate cells, viruses, and proteins using on‐chip immunoaffinity capture biotinylated antibodies, proteins, or aptamers. To accomplish this, the inner surface is modified present binding moieties desired analyte. While this approach successful in research settings, it challenging scale many modification strategies. Traditional polydimethylsiloxane (PDMS) can be effectively functionalized silane‐based methods; however, requires high...
Objective To measure Met protein content in prostate biopsies guided by fused magnetic resonance and ultrasound imaging, to soluble (sMet) concentration plasma samples from patients presenting evidence of cancer. Patients Methods 345 had drawn prior image-guided biopsy the prostate. Of these, 32% benign biopsies. 236 that were positive for adenocarcinoma (PCa), 132 treated total prostatectomy Gleason scores 6 (17%), 7, (55%), 8 (16%), or 9–10 (12%). 23% local invasion. Plasma also obtained...
Abstract Foretinib is a potent, orally available, small-molecule inhibitor of MET and VEGFR2. Significant tumor cell growth inhibition was observed preclinically following treatment in multiple models. Antitumor activity previous phase I study which foretinib dosed intermittently on days 1–5 every 14 days. This dose-escalation to evaluate daily oral administration conducted adults with solid tumors. administered until disease progression or toxicity mandated removal from the study....
Summary Triple-negative breast cancers (TNBC) are highly infiltrated by tumor-associated macrophages (TAMs) that promote tumor growth, survival, metastasis and therapeutic resistance. Although cytokines such as CCL5 have been implicated in TAM recruitment to TNBC tumors, the mechanism which cells educate TAMs is not understood. Here we show EVs both necessary sufficient for programming toward a pro-metastatic phenotype. The involves regulation of extracellular vesicles (EVs), activate TLR2...
Abstract Background: Immune-checkpoint blockade (ICB), with or without chemotherapy, is the standard of care for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). However, only a minority patients get clinical benefit from it. The combined expression PD-L1 in tumor section currently biomarker approved response prediction. Yet, its invasive nature suboptimal predictive performance underscores need new, non- surrogates immune activity undergoing ICB. Extracellular vesicles...