A5023146118- MicroRNA in disease regulation
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Cancer Immunotherapy and Biomarkers
- RNA Research and Splicing
- Immunotherapy and Immune Responses
- Advanced biosensing and bioanalysis techniques
- Cytokine Signaling Pathways and Interactions
- Lung Cancer Research Studies
- Cancer Genomics and Diagnostics
- Immune cells in cancer
- Mitochondrial Function and Pathology
- RNA Interference and Gene Delivery
- Nanoplatforms for cancer theranostics
- Cancer Cells and Metastasis
- Photoreceptor and optogenetics research
- Extracellular vesicles in disease
- Renal Transplantation Outcomes and Treatments
- Cancer Mechanisms and Therapy
- Chemokine receptors and signaling
- Breast Cancer Treatment Studies
- RNA regulation and disease
- Neuroscience and Neuropharmacology Research
- Laser-Ablation Synthesis of Nanoparticles
- Adipose Tissue and Metabolism
City of Hope
2016-2025
City Of Hope National Medical Center
2010-2025
Beckman Research Institute
2009-2021
Northwestern University
2004
Center for Neurosciences
2000
Abstract Improving effector T-cell functions is highly desirable for preventive or therapeutic interventions of diverse diseases. Signal transducer and activator transcription 3 (Stat3) in the myeloid compartment constrains Th1-type immunity, dampening natural induced antitumor immune responses. We have recently developed an vivo small interfering RNA (siRNA) delivery platform by conjugating a Toll-like receptor 9 agonist with siRNA that efficiently targets B cells. Here, we show either CpG...
Antisense oligonucleotides (ASOs) are known to trigger mRNA degradation in the nucleus via an RNase H-dependent mechanism. We have now identified a putative cytoplasmic mechanism through which ASO gapmers silence their targets when transfected or delivered gymnotically (i.e. absence of any transfection reagent). shown that can interact with Ago-2 PAZ domain and localize into GW-182 mRNA-degradation bodies (GW-bodies). The products targeted mRNA, however, not generated by Ago-2-directed...
Aptamer-drug conjugates (ApDCs) have the potential to improve therapeutic index of traditional chemotherapeutic agents due their ability deliver cytotoxic drugs specifically cancer cells while sparing normal cells. This study reports on conjugation an aptamer previously described by our group, pancreatic RNA P19. To this end, P19 was incorporated with gemcitabine and 5-fluorouracil (5-FU), or conjugated monomethyl auristatin E (MMAE) derivative maytansine 1 (DM1). The ApDCs P19-dFdCMP...
Understanding supports for cancer stem-like cells in malignant glioma may suggest therapeutic strategies their elimination. Here, we show that the Toll-like receptor TLR9 is elevated (GSC) which it contributes to growth. overexpression regulated by STAT3, required GSC maintenance. Stimulation of with a CpG ligand (CpG ODN) promoted growth, whereas silencing expression abrogated development. CpG-ODN treatment induced Frizzled4-dependent activation JAK2, thereby activating STAT3. Targeted...
Mitotic clonal expansion has been suggested as a prerequisite for adipogenesis in murine preadipocytes, but the precise role of cell proliferation during human is unclear. Using adipose tissue-derived mesenchymal stem cells an vitro model adipogenic study, group cycle regulators, including Cdk1 and CCND1, were found to be downregulated early 24 h after initiation consistently, activity was restricted first 48 induction. Cell either further inhibited using siRNAs targeting genes or enhanced...
Abstract The tumor microenvironment is composed of heterogeneous populations cells, including cancer, immune, and stromal cells. Progression growth initiation metastasis critically dependent on the reciprocal interactions between cancer cells stroma. Through RNA-Seq protein analyses, we found that cancer-associated fibroblasts derived from human breast brain express significantly higher levels chemokines CXCL12 CXCL16 than primary tumors or normal breast. To further understand interplay each...
The 5-year survival rate for pancreatic ductal adenocarcinoma (PDAC) remains dismal despite current chemotherapeutic agents and inhibitors of molecular targets. As the incidence PDAC constantly increases, more effective multidrug approaches must be made. Here, we report a novel method delivering antitumorigenic therapy in by upregulating transcriptional factor CCAAT/enhancer-binding protein-α (C/EBPα), recognized its antiproliferative effects. Small activating RNA (saRNA) duplexes designed...
Neural stem cells maintain their tumor tropism after internalizing gold nanorods. When exposed to a laser, the loaded heat up, destroying surrounding cells. As service our authors and readers, this journal provides supporting information supplied by authors. Such materials are peer reviewed may be re-organized for online delivery, but not copy-edited or typeset. Technical support issues arising from (other than missing files) should addressed Please note: The publisher is responsible content...
Chromatin-associated RNAs (caRNAs) form a relatively poorly recognized layer of the epigenome. The caRNAs reported to date are transcribed from nuclear genome. Here, leveraging recently developed assay for detection and their genomic association, we report that mitochondrial (mtRNAs) attached genome constitute subset caRNA, thus termed mt-caRNA. In four human cell types analyzed, mt-caRNAs preferentially attach promoter regions. endothelial cells (ECs), level mt-caRNA-promoter attachment...
Extracellular vesicles (EVs), membrane-encapsulated nanoparticles shed from all cells, are tightly involved in critical cellular functions. Moreover, EVs have recently emerged as exciting therapeutic modalities, delivery vectors, and biomarker sources. However, difficult to characterize, because they typically small heterogeneous size, origin, molecular content. Recent advances single EV methods addressed some of these challenges by providing sensitive tools for assessing individual...
Abstract Small cell lung cancer (SCLC) is a devastating malignancy with limited treatment options, mainly consisting of chemotherapy and/or immunotherapy. We identified the combination carboplatin (carbo) standard therapy protein phosphatase 2A (PP2A) inhibitor LB100 as potential new therapeutic approach in SCLC. Primary SCLC cells are difficult to obtain, and we therefore sought define its on-target vivo efficacy using pre-clinical H146 murine xenograft model (athymic nu/nu mice)....
Human glioblastoma (GBM) is the most aggressive malignancy of CNS, with less than 5% survival. Despite great efforts to find effective therapeutics, current options remain very limited. To develop a targeted cancer therapeutic, we selected RNA aptamers against platelet-derived growth factor receptor α (PDGFRα), which tyrosine kinase. One aptamer (PDR3) high affinity (0.25 nM) showed PDGFRα specificity and was internalized in U251-MG cells. Following treatment PDR3 aptamer, expression...
Significance The deregulation of miRNA function is critical in the pathogenesis cancer and other diseases. miRNAs noncoding RNAs (ncRNAs) tightly regulate gene expression, often cell nucleus. Heretofore, there has been no understanding that exists a general shuttling mechanism brings miRNAs, addition to therapeutic oligonucleotides siRNAs, from cytoplasm into We have identified this mechanism, which occurs response stress. Nuclear imported are functional, can potentially alter participate...
Identifying targets that are exposed on the plasma membrane of tumor cells, but expressed internally in normal is a fundamental issue for improving specificity and efficacy anticancer therpeutics. Using blind cell Systemic Evolution Ligands by EXponetial enrichment (SELEX), which untargeted SELEX, we have identified an aptamer, P15, specifically bound to human pancreatic adenocarcinoma cells. To identify aptamer binding protein, liquid chromatography tandem mass spectrometry (LC-MS/MS) was...
Background: The molecular and clinical features of KRAS-mutated lung cancer patients treated with immunotherapy have yet to be characterized, which could guide the development therapeutics targeting KRAS potential immuno-oncology treatment combinations. Research Question: Do different subtypes comutations responses overall survival (OS) checkpoint inhibitors? Study Design Methods: 87 NSCLC at City Hope who received immune inhibitors were identified analyzed retrospectively. Tumor genomic...
A web application for inferring potentially stabilizing non-bonding interactions in macromolecular structures from input atomic coordinate data is described. The core software, called Monster, comprises a PERL wrapper that takes advantage of scripts developed in-house as well established software the public domain to validate files, identify interacting residues and assign nature these interactions. results are assembled presented an intuitive interactive graphical format. Potential...
Discovery of biomarkers is critical to understand tumor heterogeneity and microenvironment. To determine differently expressed makers on cancer tissue for comprehensive profiling, the multiplexed imaging mass cytometer (IMC) which uniquely combines time-of-flight spectrometry with metal-labeling technology enable breakthrough discovery single cell level was employed investigate expression seven markers related epithelial-to-mesenchymal transition [α-smooth muscle actin (α-SMA), vimentin,...
Cerebrospinal fluid (CSF) sodium concentration increases during migraine attacks, and both CSF vitreous humor increase in the rat model. The Na,K-ATPase is a probable source of these fluxes. Since isoforms have different locations physiological roles, our objective was to establish which alpha are present at sites where homeostasis disrupted.Specific were identified tissues by immunohistochemistry blood-CSF barrier choroid plexus, blood-CSF-trigeminal meninges, blood-retina barrier,...