A5017002266- Genetic and Kidney Cyst Diseases
- Bone and Dental Protein Studies
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Epigenetics and DNA Methylation
- MicroRNA in disease regulation
- Mesenchymal stem cell research
- Liver physiology and pathology
- Immunotherapy and Immune Responses
- Liver Disease Diagnosis and Treatment
- Peptidase Inhibition and Analysis
- Hedgehog Signaling Pathway Studies
- Pancreatic function and diabetes
- Proteoglycans and glycosaminoglycans research
- Folate and B Vitamins Research
- Digestive system and related health
- Pancreatic and Hepatic Oncology Research
- Cancer Research and Treatments
- Tissue Engineering and Regenerative Medicine
- Organ Transplantation Techniques and Outcomes
- Fibroblast Growth Factor Research
- Pediatric Hepatobiliary Diseases and Treatments
- DNA Repair Mechanisms
- Virus-based gene therapy research
- Immune Cell Function and Interaction
- Chemokine receptors and signaling
Hormel (United States)
2017-2025
University of Minnesota
2017-2025
University of Minnesota Medical Center
2020-2023
Austral University
2013-2018
University of Miami
2017
Consejo Nacional de Investigaciones Científicas y Técnicas
2007-2016
Institute for Medical Research
2016
University of Tennessee at Knoxville
2010
Liver cirrhosis involves chronic wound healing and fibrotic processes. Mesenchymal stromal cells (MSCs) are multipotent adult progenitor that used as vehicles of therapeutic genes. Insulin growth factor like-I (IGF-I) was shown to counteract liver fibrosis. We aimed at analyzing the effect applying IGF-I overexpressing mouse bone marrow-derived MSCs on hepatic Fibrosis induced by thioacetamide application or bile duct ligation. engineered produce green fluorescent protein (GFP) (AdGFP-MSCs)...
Cholangiocytes normally express primary cilia, a multisensory organelle that detects signals from the cellular environment. Cilia are significantly reduced in cholangiocarcinoma (CCA) by mechanism involving overexpression of histone deacetylase 6 (HDAC6). Despite HDAC6 CCA, we found no differences its mRNA level, suggesting posttranscriptional regulation, possibly microRNAs (miRNAs). Here, describe at least two HDAC6‐targeting miRNAs, miR‐433 and miR‐22, down‐regulated CCA both vitro vivo ....
Cirrhosis is characterized by an excessive accumulation of extracellular matrix components including hyaluronic acid (HA) and widely considered a preneoplastic condition for hepatocellular carcinoma (HCC).4-Methylumbelliferone (4MU) inhibitor HA synthesis has anticancer activity in orthotopic HCC model with underlying fibrosis.Our aim was to explore the effects inhibition 4MU orally administered on tumor microenvironment.Hepa129 cells were inoculated orthotopically C3H/HeJ male mice fibrosis...
ABSTRACT Primary cilia have been considered tumor-suppressing organelles in cholangiocarcinoma (CCA), though the mechanisms behind their protective role are not fully understood. This study investigates how loss of primary affects DNA damage response (DDR) and repair processes CCA. Human cholangiocyte cell lines were used to examine colocalization proteins at assess impact experimental deciliation on pathways. Deciliation was induced using shRNA knockdown or CRISPR knockout IFT20, IFT88,...
Primary cilia, hair-like projections on the surface of various cell types, play crucial roles in sensing and regulating environmental cues within liver, particularly among cholangiocytes. These structures detect changes bile composition, flow, other biochemical signals, integrating this information to modulate cellular processes. Dysfunction cholangiocyte cilia—whether due structural abnormalities or genetic mutations—has been linked an array cholangiopathies ciliopathies. include conditions...
Several reports described the migration of human mesenchymal stromal cells (MSCs) towards tumor-released factors. Autocrine motility factor (AMF) is produced by several tumors including hepatocellular carcinoma (HCC). The aim this study was to analyze AMF involvement on MSC HCC.Production HCC evaluated western analysis. effects MSCs from different sources (bone marrow, adipose tissue and perivascular umbilical cord) were analyzed using in vitro assay; metalloproteinase 2 (MMP2) activity...
Introduction Secreted Protein, Acidic and Rich in Cysteine (SPARC) is a matricellular protein involved many biological processes found over-expressed cirrhotic livers. By mean of genetic approach we herein provide evidence from different vivo liver disease models suggesting profibrogenic role for SPARC. Methods Two fibrosis, based on TAA administration bile duct ligation, were developed SPARC wild-type (SPARC+/+) knock-out (SPARC−/−) mice. Hepatic expression was analyzed by qPCR. Fibrosis...
This work identifies novel targets against primary ciliary disassembly that can lead to new cholangiocarcinoma therapeutic strategies. Furthermore, loss has been described in different tumors, increasing the significance of our research.
The primary cilium, an organelle that protrudes from cell surfaces, is essential for sensing extracellular signals. With disturbed cellular communication and chronic liver pathologies, this organelle's dysfunctions have been linked to disorders, including polycystic disease cholangiocarcinoma. goal of study was elucidate the relationship between cilia crucial regulator proliferation, epidermal growth factor receptor (EGFR) signaling pathway, which has associated with various clinical conditions.
Cholangiocytes, the epithelial cells lining biliary tree in liver, express primary cilia that can detect several kinds of environmental signals and then transmit this information into cell. We have reported are significantly reduced cholangiocarcinoma (CCA) experimental deciliation normal induces a malignant‐like phenotype with increased proliferation, anchorage‐independent growth, invasion, migration. Here, we tested hypothesis chemosensory function cholangiocyte acts as mechanism for tumor...
Abstract Background Cirrhosis is a major health problem worldwide and new therapies are needed. Hepatic macrophages (hMø) have pivotal role in liver fibrosis, being able to act both its promotion resolution. It well-known that mesenchymal stromal cells (MSCs) can modulate the immune/inflammatory cells. However, effects of MSCs over hMø context fibrosis remain unclear. We previously described evidence antifibrotic vivo applying MSCs, which were enhanced by forced overexpression insulin-like...
Mechanisms that control progression from simple steatosis to steato-hepatitis and fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) are unknown. SPARC, a secreted matricellular protein, is over-expressed the under chronic injury. Contribution of SPARC accumulation severity largely unknown NAFLD. We assessed hypothesis increased livers more necrosis inflammation could be associated fibrosis. qrt-PCR, immunohistochemistry, ELISA were employed localize quantify changes 62...
We have previously demonstrated that a low dose of cyclophosphamide (Cy) combined with gene therapy interleukin-12 (AdIL-12) has synergistic, although limited, antitumoral effect in mice colorectal carcinoma. The main mechanism involved the efficacy Cy+AdIL-12 was induction specific immune response mediated by cytotoxic T lymphocytes. Our current aims were to evaluate effects 4-methylumbelliferone (4Mu), selective inhibitor hyaluronan (HA) synthesis, on tumor microenvironment (TME) and...
Hepatocellular carcinoma (HCC) is the third cause of cancer-related death worldwide. Unfortunately, incidence and mortality associated with HCC are increasing. Therefore, new therapeutic strategies urgently needed use mesenchymal stromal cells (MSCs) as carrier genes emerging a promising option. Different sources MSCs being studied for cell therapy bone marrow-derived most extensively explored; however, birth associated-tissues represent very source. The aim this work was to compare in vitro...
It is well established that Cholangiocarcioma (CCA) drug resistance plays a crucial role in the spread and survival of cancer cells. The major enzyme nicotinamide-adenine dinucleotide (NAD+)-mediated pathways, nicotinamide phosphoribosyltransferase (NAMPT), essential for cell metastasis. Previous research has shown targeted NAMPT inhibitor FK866 reduces viability triggers death; however, whether affects CCA not been addressed before. We show herein expressed cells, suppresses capacity cells...
We have shown that ex vivo pre-conditioning of bone marrow-derived dendritic cells (DC) with low molecular weight hyaluronan (LMW HA) induces antitumor immunity against colorectal carcinoma (CRC) in mice. In the present study we investigated effects LMW HA priming on human-tumor-pulsed monocytes-derived (DC/TL) obtained from healthy donors and patients CRC. treatment resulted an improved maturation state DC/TL enhanced mixed leucocyte reaction activity vivo. Importantly, increased their...
Sirtuin 1 (SIRT1) is a complex NAD+ -dependent protein deacetylase known to act as tumor promoter or suppressor in different cancers. Here, we describe mechanism of SIRT1-induced destabilization primary cilia cholangiocarcinoma (CCA).A significant overexpression SIRT1 was detected human CCA specimens and cells including HuCCT1, KMCH, WITT1 compared with normal cholangiocytes (H69 NHC). Small interfering RNA (siRNA)-mediated knockdown HuCCT1 induced formation, whereas suppressed ciliary...
Background and Aims Polycystic liver diseases (PLDs) are genetic disorders characterized by progressive development of symptomatic biliary cysts. Current surgical pharmacological approaches ineffective, transplantation represents the only curative option. Ursodeoxycholic acid (UDCA) histone deacetylase 6 inhibitors (HDAC6is) have arisen as promising therapeutic strategies, but with partial benefits. Approach Results Here, we tested an approach based on design, synthesis, validation a family...