- Helicobacter pylori-related gastroenterology studies
- Digestive system and related health
- Hedgehog Signaling Pathway Studies
- Cancer Cells and Metastasis
- IL-33, ST2, and ILC Pathways
- Lung Cancer Treatments and Mutations
- Eosinophilic Esophagitis
- Immune Cell Function and Interaction
- Fibroblast Growth Factor Research
- Cytokine Signaling Pathways and Interactions
- Genetic factors in colorectal cancer
- Lung Cancer Research Studies
- Immune cells in cancer
- Gastric Cancer Management and Outcomes
- Tumors and Oncological Cases
- Peptidase Inhibition and Analysis
- Epigenetics and DNA Methylation
- Cancer therapeutics and mechanisms
- Galectins and Cancer Biology
- Gastrointestinal disorders and treatments
- HER2/EGFR in Cancer Research
- Liver physiology and pathology
- Inflammatory Bowel Disease
- Lung Cancer Diagnosis and Treatment
- Birth, Development, and Health
Children's Hospital of Los Angeles
2015-2024
University of Southern California
2015-2024
Krankenhaus der Elisabethinen
2015-2022
Imperial College London
2021
University of Michigan
2018
University of Cincinnati Medical Center
2009-2015
University of Cincinnati
2009-2015
Johns Hopkins Medicine
2008
Johns Hopkins University
2008
University of Arizona
1987
Abstract The intestinal epithelium constitutes a system of constant and rapid renewal triggered by proliferation stem cells (ISCs), is an ideal for studying cell proliferation, migration, differentiation. Primary cultures have proven to be promising unraveling the mechanisms involved in homeostasis. In 2009, Sato et al. established long‐term primary culture generate epithelial organoids (enteroids) with crypt‐ villus‐like domains representing complete census progenitors differentiated cells....
The cytotoxin-associated gene (Cag) pathogenicity island is a strain-specific constituent of Helicobacter pylori (H. pylori) that augments cancer risk. CagA translocates into the cytoplasm where it stimulates cell signaling through interaction with tyrosine kinase c-Met receptor, leading cellular proliferation. Identified as potential gastric stem marker, cluster-of-differentiation (CD) CD44 also acts co-receptor for c-Met, but whether plays functional role in H. pylori-induced epithelial...
<h3>Objective</h3> <i>Helicobacter pylori</i> strains that express the oncoprotein CagA augment risk for gastric cancer. However, precise mechanisms through which <i>cag</i><sup>+</sup> heighten cancer have not been fully delineated and model systems recapitulate niche are critical understanding pathogenesis. Gastroids three-dimensional organ-like structures provide unique opportunities to study host-<i>H. interactions in a preclinical model. We used gastroids inform direct vitro studies...
An in vitro approach to study gastric development is primary mouse-derived epithelium cultured as three-dimensional spheroids known organoids. We have devised two unique fundic-derived organoid cultures: model 1 for the expansion of fundic stem cells, and 2 maintenance mature cell lineages. Organoids maintained co-culture with immortalized stomach mesenchymal cells express robust numbers surface pit, mucous neck, chief, endocrine parietal cells. Histamine induced a significant decrease...
Maternal adiponectin levels are inversely correlated to birth weight, suggesting that maternal limits fetal growth. We hypothesized full-length (fADN) infusion in pregnant mice down-regulates placental amino acid transporters and decreases Starting at embryonic day (E) 14.5, fADN (0.62 ± 0.02 μg (g body weight)(−1) day(−1), n = 7) or vehicle (control, 9) were infused C57/BL6 by mini-osmotic pump. At E18.5, dams killed homogenates trophoblast plasma membrane (TPM) vesicles prepared. Infusion...
Abstract Efficient clearance of pro-inflammatory macrophages from tissues after resolution a challenge is critical to prevent prolonged inflammation. Defects in can contribute conditions such as inflammatory bowel disease, and thus may be therapeutically targetable. However, the signaling pathways that induce termination are incompletely defined. We tested whether ErbB4 receptor tyrosine kinase, previously not known have role macrophage biology, involved this process. In vitro , activation...
Helicobacter pylori (H. pylori) is a pathogen contributing to peptic inflammation, ulceration, and cancer. A crucial step in the pathogenic sequence when bacterium first interacts with gastric tissue, an event that poorly understood vivo. We have shown luminal space adjacent epithelial damage microenvironment, we hypothesized this microenvironment might enhance H. colonization. Inoculation 106 (wild-type Sydney Strain 1, SS1) significantly delayed healing of acetic-acid induced ulcers at Day...
Leucine-rich repeat-containing G-protein coupled receptor 5-expressing (Lgr5(+)) cells have been identified as stem/progenitor in the circumvallate papillae, and single cultured Lgr5(+) give rise to taste cells. Here we use papilla tissue establish a three-dimensional culture system (taste bud organoids) that develops phenotypic characteristics similar native tissue, including multilayered epithelium containing outer layers inner layers. Furthermore, characterization of cell cycle progenitor...
Background Helicobacter pylori ( H. ) infection leads to acute induction of Sonic Hedgehog (Shh) in the stomach that is associated with initiation gastritis. The mechanism by which induces Shh unknown. a target gene transcription factor Nuclear Factor‐κB NF κB). We hypothesize κB mediates ‐induced Shh. Materials and Methods To visualize ligand expression response vivo, we used mouse model expresses fused green fluorescent protein (Shh:: GFP mice) place wild‐type In vitro, changes were...
Conventional medicine and homeopathy work well together. Quality of life improves with additive in patients non-small cell lung cancer (NSCLC). Survival NSCLC.
Abstract Dynamic regulation of intestinal cell differentiation is crucial for both homeostasis and the response to injury or inflammation. Sprouty2, an intracellular signaling regulator, controls pathways including PI3K MAPKs that are implicated in dysregulated inflammatory bowel disease. Here, we ask whether Sprouty2 secretory colitis. We report colonic epithelial deletion leads expanded tuft goblet populations. loss induces PI3K/Akt signaling, leading GSK3β inhibition interleukin (IL)-33...
Introduction: Rearranged during transfection (RET) gene fusions are rare genetic drivers in non-small cell lung cancer (NSCLC). Selective RET-inhibitors such as selpercatinib have shown therapeutic activity early clinical trials; however, their efficacy the real-world setting is unknown. Methods: A retrospective and safety analysis was performed on data from RET fusion-positive NSCLC patients who participated a access program (named patient protocol) between August 2019 January 2021....
Patients with non-small cell lung cancer (NSCLC) presenting mesenchymal-epithelial transition (MET) exon 14 skipping mutation have an unfavorable prognosis standard treatments. Capmatinib is a selective MET inhibitor, which showed promising efficacy in this patient population early trials.We performed retrospective, international, multicenter and safety analysis patients NSCLC treated capmatinib access program between March 2019 December 2021.Data from 81 advanced mutated first- or...
Randomized controlled trials have demonstrated that afatinib is a suitable treatment option for patients with epidermal growth factor receptor mutation-positive (EGFRm +) non-small cell lung cancer (NSCLC). However, such studies often exclude treated in routine clinical practice. We report interim results from Phase 3b, open-label, multicenter, single-arm, exploratory trial, which was investigated real-world setting.Patients EGFRm + tyrosine kinase inhibitor (TKI)-naïve NSCLC received 40 mg...
Sonic Hedgehog (Shh), secreted from gastric parietal cells, contributes to the regeneration of epithelium. The recruitment macrophages plays a central role in regenerative process. mechanism that regulates macrophage response injury is largely unknown. Here we tested hypothesis Shh stimulates chemotaxis injured epithelium and regeneration. A mouse model expressing myeloid cell-specific deletion Smoothened (LysMcre/+;Smof/f) was generated using transgenic mice bearing loxP sites flanking Smo...
In the stomach, strictly regulated cell adherens junctions are crucial in determining epithelial differentiation. Sonic Hedgehog (Shh) regulates differentiation adult stomach. We sought to identify whether Shh plays a role regulating junction protein E-cadherin as mechanism for Mouse nontumorigenic gastric (IMGE-5) cells treated with signaling inhibitor cyclopamine and anti-Shh 5E1 antibody or transduced short hairpin RNA against Skinny (IMGE-5(Ski)) were cultured. A mouse model expressing...
In clinical practice, patients with anaplastic lymphoma kinase (ALK)-rearrangement–positive non–small-cell lung cancer commonly receive sequential treatment ALK tyrosine inhibitors. The third-generation agent lorlatinib has been shown to inhibit a wide range of resistance mutations and thus offers potential benefit in later lines, although real-world data are lacking. This multicenter study retrospectively investigated later-line, use advanced ALK- or ROS1-positive cancer. Fifty-one...