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| http://dx.doi.org/10.1016/j.jcmgh.2022.06.004 | DOI Listing |
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High-throughput formulation of reproducible 3D cancer microenvironments for drug testing in myeloid leukemia.
Biofabrication
December 2024
Institute of Physical Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, 01-224 Warsaw, Poland.
Leukemic microenvironment has been recognized as a factor that strongly supports the mechanisms of resistance. Therefore, targeting the microenvironment is currently one of the major directions in drug development and preclinical studies in leukemia. Despite the variety of available leukemia 3D culture models, the reproducible generation of miniaturized leukemic microenvironments, suitable for high-throughput drug testing, has remained a challenge.
View Article and Find Full Text PDFTwo-phase mechanism in the treatment of corneal stromal fibrosis with topical losartan.
Exp Eye Res
May 2024
Cole Eye Institute, The Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, USA. Electronic address:
Recent studies in rabbits and case reports in humans have demonstrated the efficacy of topical losartan in the treatment of corneal scarring fibrosis after a wide range of injuries, including chemical burns, infections, surgical complications, and some diseases. It is hypothesized that the effect of losartan on the fibrotic corneal stroma occurs through a two-phase process in which losartan first triggers the elimination of myofibroblasts by directing their apoptosis via inhibition of extracellular signal-regulated kinase (ERK)-mediated signal transduction, and possibly through signaling effects on the viability and development of corneal fibroblast and fibrocyte myofibroblast precursor cells. This first step likely occurs within a week or two in most corneas with fibrosis treated with topical losartan, but the medication must be continued for much longer until the epithelial basement membrane (EBM) is fully regenerated or new myofibroblasts will develop from precursor cells.
View Article and Find Full Text PDFDriving role of head and neck cancer cell secretome on the invasion of stromal fibroblasts: Mechanistic insights by phosphoproteomics.
Biomed Pharmacother
February 2023
Department of Otolaryngology, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain; Instituto Universitario de Oncología del Principado de Asturias (IUOPA), University of Oviedo, Oviedo, Spain; CIBERONC, Instituto de Salud Carlos III, Madrid, Spain. Electronic address:
Background: Cancer-associated fibroblasts (CAFs) are major players in tumor-stroma communication, and participate in several cancer hallmarks to drive tumor progression and metastatic dissemination. This study investigates the driving effects of tumor-secreted factors on CAF biology, with the ultimate goal of identifying effective therapeutic targets/strategies for head and neck squamous cell carcinomas (HNSCC).
Methods: Functionally, conditioned media (CM) from different HNSCC-derived cell lines and normal keratinocytes (Kc) were tested on the growth and invasion of populations of primary CAFs and normal fibroblasts (NFs) using 3D invasion assays in collagen matrices.
Three-dimensional growth reveals fine-tuning of 5-lipoxygenase by proliferative pathways in cancer.
Life Sci Alliance
May 2023
Institute of Pharmaceutical Chemistry, Goethe University, Frankfurt, Germany
The leukotriene (LT) pathway is positively correlated with the progression of solid malignancies, but the factors that control the expression of 5-lipoxygenase (5-LO), the central enzyme in LT biosynthesis, in tumors are poorly understood. Here, we report that 5-LO along with other members of the LT pathway is up-regulated in multicellular colon tumor spheroids. This up-regulation was inversely correlated with cell proliferation and activation of PI3K/mTORC-2- and MEK-1/ERK-dependent pathways.
View Article and Find Full Text PDFTissue CD14CD8 T cells reprogrammed by myeloid cells and modulated by LPS.
Nature
February 2023
Division of Infection & Immunity, Institute of Immunity & Transplantation, University College London, London, UK.
Article Synopsis
- The liver is constantly exposed to bacterial products from the gut but usually maintains a tolerant state; understanding how this tolerance can shift to immunity or pathology is crucial for improving liver disease treatments.
- A specific type of T cell, called CD14CD8 T cells, is found in high numbers in the liver, particularly in liver transplants and conditions like cirrhosis, and they show unique activation and immunomodulatory capabilities.
- These CD14CD8 T cells can be influenced by bacterial components and local tissue signals, enhancing their ability to interact with the environment and potentially improve anti-tumor and antiviral responses.
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