The disorganized and inefficient tumor vasculature is a major obstacle to the delivery and efficacy of antineoplastic treatments. Antiangiogenic agents can normalize the tumor vessels, improving vessel function and boosting the distribution and activity of chemotherapy. The type III repeats (T3R) domain of thrombospondin-1 contains different potential antiangiogenic sequences. We therefore hypothesized that it might affect the tumor vasculature. Ectopic expression of the T3R domain by the tumor cells or by the host, or administration of recombinant T3R, delayed the in vivo growth of experimental tumors. Tumors presented marked reorganization of the vasculature, with abundant but smaller vessels, associated with substantially less necrosis. Mechanistically, the use of truncated forms of the domain, containing different active sequences, pointed to the FGF2/FGFR/ERK axis as a target for T3R activity. Along with reduced necrosis, the expression of T3R promoted tumor distribution of chemotherapy (paclitaxel), with a higher drug concentration and more homogeneous distribution, as assessed by HPLC and MALDI imaging mass spectrometry. T3R-expressing tumors were more responsive to paclitaxel and cisplatin. This study shows that together with its known role as a canonical inhibitor of angiogenesis, thrombospondin-1 can also remodel tumor blood vessels, affecting the morphological and functional properties of the tumor vasculature. The ability of T3R to reduce tumor growth and improve the response to chemotherapy opens new perspectives for therapeutic strategies based on T3R to be used in combination therapies.
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http://dx.doi.org/10.1016/j.matbio.2021.10.001 | DOI Listing |
Biotechnol J
December 2024
Department of Biomedical Engineering, Tulane University, New Orleans, USA.
Microphysiological systems (MPS) containing perfusable vascular beds unlock the ability to model tissue-scale elements of vascular physiology and disease in vitro. Access to inexpensive stereolithography (SLA) 3D printers now enables benchtop fabrication of polydimethylsiloxane (PDMS) organ chips, eliminating the need for cleanroom access and microfabrication expertise, and can facilitate broader adoption of MPS approaches in preclinical research. Rapid prototyping of organ chip mold designs accelerates the processes of design, testing, and iteration, but geometric distortion and surface roughness of SLA resin prints can impede the development of standardizable manufacturing workflows.
View Article and Find Full Text PDFJ Neurooncol
December 2024
Department of Medicine, University of Toronto, Toronto, ON, Canada.
Purpose: To review applications of cerebral spinal fluid (CSF) biomarkers for the diagnosis, monitoring and treatment of leptomeningeal metastatic disease (LMD) among patients with metastatic solid tumors.
Methods: A narrative review identified original research related to CSF biomarkers among patients with metastatic solid tumors and LMD. Pre-clinical research (e.
Eur J Med Res
December 2024
Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
Colorectal cancer (CRC) is currently ranked as the third most common type of cancer, contributing significantly to mortality and morbidity worldwide. Epigenetic and genetic changes occurred during CRC progression resulted in the cell proliferation, cancer progression, angiogenesis, and invasion. Angiogenesis is one of the crucial steps during cancer progression required for the delivery of essential nutrients to cancer cells and removes metabolic waste.
View Article and Find Full Text PDFEur Radiol
December 2024
Depatment of Radiology, West China Hospital, Sichuan University, Chengdu, China.
Objective: Dual-layer spectral detector CT (DLCT) has several advantages in clinical practice, this study aims to reveal the clinical applications of DLCT in digestive system diseases.
Materials And Methods: We searched PubMed and Cochrane Reviews for articles published from January 1, 2010 to May 31, 2024, using the terms "dual-layer spectral detector CT" or "dual-layer CT" combined with "hepatic fat" or "hepatic fibrosis" "hepatocellular carcinoma" or "pancreatic ductal adenocarcinoma" or "pancreatic neuroendocrine tumors" or "gastric cancer" or "colorectal cancer" or "Crohn's disease" or "bowel ischemia" or "acute abdominal conditions".
Results: DLCT consists of a top layer sensitive to lower-energy photons and a bottom layer sensitive to higher-energy photons.
Endocr Relat Cancer
December 2024
M Maugham-Macan, Biomedical Science, University of the Sunshine Coast, Sippy Downs, Australia.
Bone is a common and debilitating site for metastatic cancer cell expansion. Skeletal metastasis is a multistage process, with primary stages of circulating tumour cells, progressing to a dormant state in vasculature and bone marrow niches, followed by tumorigenic reactivation, proliferation, and finally bone destruction. The frequency of bone metastasis is reconciled in Paget's "seed and soil" hypothesis, where a conducive microenvironment (bone niche) is essential for cancer cell colonisation.
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