Oral administration of forphenicinol, S-2-(3-hydroxy-4-hydroxymethylphenyl)glycine, inhibited the growth of EL4 lymphoma by both pre- and posttreatment. Although some mice given this drug rejected the tumor, they could not obtain acquired immunity against the tumor. Macrophages taken from normal mice did not inhibit the growth of EL4 cells in vivo (tumor neutralization assay) or in vitro (cytostasis assay). Forphenicinol induced effector activity in such macrophages neither in vitro nor in vivo. Forphenicinol administration to mice bearing EL4 activated macrophages to inhibit the growth of EL4 in vitro and in vivo. Moreover, it stimulated the tumor growth-inhibitory activity of splenocytes in both tumor-free and tumor-bearing mice.
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Proc Natl Acad Sci U S A
January 2025
Department of Pathology, University of California San Diego, La Jolla, CA 92093.
We hypothesized that a strategy employing tissue-specific endothelial cells (EC) might facilitate the identification of tissue- or organ-specific vascular functions of ubiquitous metabolites. An unbiased approach was employed to identify water-soluble small molecules with mitogenic activity on choroidal EC. We identified adenosine diphosphate (ADP) as a candidate, following biochemical purification from mouse EL4 lymphoma extracts.
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Neuroinflammation Research Lab, Faculty of Life Sciences and Biotechnology, South Asian University, Rajpur Road, Maidan Garhi, New Delhi, 110068, India.
The pro-inflammatory enzyme cyclooxygenase 2 (COX-2) has been known to impart metastatic property to cancer cells. However, blocking of COX-2 with nonsteroidal anti-inflammatory drugs or COX-2-specific inhibitors has failed in clinical trials due to adverse effects associated with their prolonged use. We have previously shown that extracellular ATP (eATP), a major component of the tumor microenvironment, enhances COX-2 expression several-fold, both in macrophages and in various cancer cells, by acting on purinergic (P2) receptors.
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Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK
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Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
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