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Role of macrophage targeting in the antitumor activity of trabectedin

, : Role of macrophage targeting in the antitumor activity of trabectedin. Cancer Cell 23(2): 249-262

There is widespread interest in macrophages as a therapeutic target in cancer. Here, we demonstrate that trabectedin, a recently approved chemotherapeutic agent, induces rapid apoptosis exclusively in mononuclear phagocytes. In four mouse tumor models, trabectedin caused selective depletion of monocytes/macrophages in blood, spleens, and tumors, with an associated reduction of angiogenesis. By using trabectedin-resistant tumor cells and myeloid cell transfer or depletion experiments, we demonstrate that cytotoxicity on mononuclear phagocytes is a key component of its antitumor activity. Monocyte depletion, including tumor-associated macrophages, was observed in treated tumor patients. Trabectedin activates caspase-8-dependent apoptosis; selectivity for monocytes versus neutrophils and lymphocytes is due to differential expression of signaling and decoy TRAIL receptors. This unexpected property may be exploited in different therapeutic strategies.
Trabectedin is a recently approved antitumor agent of marine origin Trabectedin activates caspase-8-dependent apoptosis exclusively in myelomonocytes In vivo trabectedin reduces monocytes and TAM, and related angiogenesis Depletion of TAM is a key component of the antitumor efficacy of trabectedin.


PMID: 23410977

DOI: 10.1016/j.ccr.2013.01.008

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Suzuki, N.; Ohta, K.; Horiuchi, T.; Takizawa, H.; Ueda, T.; Kuwabara, M.; Shiga, J.; Ito, K., 1996: T lymphocytes and silica-induced pulmonary inflammation and fibrosis in mice. Background: Silica-induced pulmonary inflammation and fibrosis in animals provides a good model for chronic pulmonary inflammation and fibrosis. Although lymphocytes are implicated in the pathogenesis of pulmonary fibrosis, experimental models usi...

Ebeling, W.; Czajkowski, G., 1976: Phase separation in bi stable enzyme reaction systems. For bistable enzyme reactions with substrate inhibition the possibility of a spontaneous spatial phase separation was investigated. For special values of the reaction parameters the system divides in 2 phases with different substrate concentration...

Haridas, R.P., 2012: Humphry Davy. Anesthesiology 116(1): 225; Author Reply 225-6

Kurmani, S.; Squire, I., 2017: Acute Heart Failure: Definition, Classification and Epidemiology. The purpose of this review is to describe the extent and scope of acute heart failure (AHF), place it within its clinical context and highlight some of the difficulties in defining it as a pathophysiological entity. A diagnosis of AHF is made when...

Harada, N.; Nakayama, M.; Nakano, H.; Fukuchi, Y.; Yagita, H.; Okumura, K., 2002: Pro-inflammatory effect of TWEAK/Fn14 interaction on human umbilical vein endothelial cells. TWEAK, a member of the TNF family, induces cell death in some tumor cell lines, but also induces proliferation of endothelial cells and angiogenesis. Recently, fibroblast growth factor-inducible 14 (Fn14) has been identified to be a TWEAK receptor...

Kerr, S.J.; Armati, P.J.; Pemberton, L.A.; Smythe, G.; Brew, B.J., 1997: Kynurenine pathway inhibition with 6-chloro-D-tryptophan reduces neurotoxicity of HIV-1 infected macrophage supernatants. Neurology 48(3 SUPPL 2): A94

Shalipina, V.G.; Kruchinina, N.A.; Garina, I.A.; Rakitskaia, V.V., 1993: The effect of a psychoemotional load on the activity of the sympathetic-adrenal system in subjects with different levels of arterial pressure. Subjects with initially increased level of arterial pressure were shown to have a higher contents of vasopressin in the blood plasma and of cortisol in the saliva. All the subjects revealed an increased systolic and diastolic blood pressure in res...

Kant, L.; Yilmaz, O.; Taskiran, D.; Kulali, B.; Furedy, J.J.; Demirgören, S.; Pögün, S., 2001: Sexually dimorphic cognitive style, female sex hormones, and cortical nitric oxide. Recent studies using the water maze (WM) found marked sex differences in behavioural strategy employed in place learning tasks in adult rats. When a change in the platform position is introduced following learning the place of a platform (visible...

Gatien, M.L.; Hotchkiss, A.K.; Dhabhar, F.S.; Nelson, R.J., 2005: Skeleton photoperiods alter delayed-type hypersensitivity responses and reproductive function of Siberian hamsters (Phodopus sungorus). Photoperiod (day length) can modulate immune function. Whether these photoperiodic effects on immune function are mediated directly by a circadian photoperiodic time measurement system or indirectly by nonspecific (e.g. stressful) effects of light...

Anonymous, 1905: Just Keep Hammering. California State Journal of Medicine 3(1): 2-2