The aim of the study was to determine the tumorigenic potential of two cell lines established from N-nitrosodimethylamine induced rat hepatocarcinoma (HeDe) and mesenchymal renal tumors (NeDe). The basis of the distinction is that human cancers are known to overexpress facilitative GLUT transporters and TGF-beta1 protein. These proteins are linked to the increased metabolic energy consumption indicating uncontrolled growth and proliferation. We have assayed not only the expression of GLUT-1, GLUT-3 and TGF-beta1 proteins, but also the uptake of 2-fluoro-[18F]-2-deoxy-D-glucose (18FDG), a tracer for cancer diagnosis. Western blot analysis and whole body autoradiography were used to measure the 18FDG uptake of tumor cells. Elevated 18FDG uptake was measured in both tumor cell lines. Whole body autoradiography provided evidence that the uptake of 18FDG was lower in the necrotic inner part than in the more vascularized outer parts of primary hepatocarcinoma and mesenchymal renal tumors. GLUT-1 overexpression in hepatocarcinoma tumor, and high levels of GLUT-3 were found in the NeDe cell line and in the mesenchymal renal tumor. TGF-beta-1 was overexpressed in hepatocarcinoma and mesenchymal renal tumors. In vitro and in vivo parameters support the view that the tumorigenic potential of cancer cells cannot be determined by the expression of a single parameter such as the expression of either GLUT-1, GLUT-3 or 18FDG uptake. Besides the tumorigenic potential of the hepatocarcinoma, the high metabolic activity of the renal tumor indicated by its 18FDG uptake, GLUT-3 and TGF-beta1 expression, the mesenchymal renal tumor induced by N-nitroso-dimethylamine is not a benign, but an an aggressive renal carcinoma.
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http://dx.doi.org/10.14670/HH-25.309 | DOI Listing |
Nat Commun
January 2025
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
We conducted a phase I trial to determine the optimal dose of triplet therapy with the tyrosine kinase inhibitor sitravatinib plus nivolumab plus ipilimumab in 22 previously untreated patients with advanced clear cell renal cell carcinoma. The primary endpoint was safety. Secondary endpoints were objective response rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), 1-year survival probability, and sitravatinib pharmacokinetics.
View Article and Find Full Text PDFEcotoxicol Environ Saf
January 2025
Institute of Combined Injury, State Key Laboratory of Trauma and Chemical Poisoning, Military Key Laboratory of Nanomedicine, Department of Military Preventive Medicine, Army Medical University, Chongqing 400038, China. Electronic address:
Uranium poisoning, particularly from exposure to Depleted Uranium (DU), occurs when uranyl ions enter the bloodstream and bind primarily to transferrin, osteopontin, and albumin before entering cells via corresponding receptors on renal tubular membranes, leading to cellular damage. Uranium poisoning remains a significant clinical challenge, with no ideal treatment currently available. In this study, we investigate the therapeutic potential of human umbilical cord-derived mesenchymal stem cell exosomes (MSC-EXs) in mice exposed to DU.
View Article and Find Full Text PDFCells
January 2025
Division of Nephrology & Hypertension, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA.
Metabolic syndrome (MetS) is associated with low-grade inflammation, which can be exacerbated by renal artery stenosis (RAS) and renovascular hypertension, potentially worsening outcomes through pro-inflammatory cytokines. This study investigated whether mesenchymal stem/stromal cells (MSCs) could reduce fat inflammation in pigs with MetS and RAS. Twenty-four pigs were divided into Lean (control), MetS, MetS + RAS, and MetS + RAS + MSCs.
View Article and Find Full Text PDFJ Transl Med
January 2025
Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Qingchun Road 79, Hangzhou, Zhejiang, 310003, China.
Background: The most common malignant type of kidney cancer is clear cell renal cell carcinoma (ccRCC). The expression levels of hyaluronan-mediated motility receptor (HMMR) in many tumor types are significantly elevated. HMMR is closely associated with tumor-related progression, treatment resistance, and poor prognosis, and has yet to be fully investigated in terms of its expression patterns and molecular mechanisms of action in ccRCC.
View Article and Find Full Text PDFJ Transl Med
January 2025
Department of Basic Medical Sciences, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310058, China.
Background: The partial epithelial-mesenchymal transition (EMT) is emerging as a significant mechanism in diabetic nephropathy (DN). LOX is a copper amine oxidase conventionally thought to act by crosslinking collagen. However, the role of LOX in partial EMT and fibrotic progression in diabetic nephropathy has not been investigated experimentally.
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