Effects of selective endothelin ET A receptor antagonists on endothelin-1-induced potentiation of cancer pain

Yuyama, Hironori; Koakutsu, Akiko; Fujiyasu, Noriko; Tanahashi, Masayuki; Fujimori, A.; Sato, Shuichi; Shibasaki, Kumiko; Tanaka, Shohei; Sudoh, Katsumi; Sasamata, Masao; Miyata, Keiji

doi:10.1016/j.ejphar.2004.04.016

Cited by 38 publications

(20 citation statements)

References 26 publications

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“…In these studies, the neutralization of NGF with blocking antibodies or small molecule inhibitors decreased nociceptive guarding behaviors in mice implanted with prostatic carcinoma or osteolytic sarcoma cells within the bone medullary cavity 21, 22, 23. Similarly, ET‐1 signaling blockade with small molecule inhibitors in tumor‐bearing mice alleviated painful sensations induced by the osteolytic growth of prostatic carcinoma or bone sarcoma cells 24, 25. Although inflammatory eicosanoids, particularly PGE2, have long been recognized to participate in nociceptor sensitization associated with inflammatory disorders, recent investigations have directly linked PGE2 with tumor‐induced osteolysis and bone cancer pain 26, 27, 28.…”

Section: Discussionmentioning

confidence: 98%

Expression of Nociceptive Ligands in Canine Osteosarcoma

Shor

Fadl-Alla

Pondenis

et al. 2015

Veterinary Internal Medicne

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BackgroundCanine osteosarcoma (OS) is associated with localized pain as a result of tissue injury from tumor infiltration and peritumoral inflammation. Malignant bone pain is caused by stimulation of peripheral pain receptors, termed nociceptors, which reside in the localized tumor microenvironment, including the periosteal and intramedullary bone cavities. Several nociceptive ligands have been determined to participate directly or indirectly in generating bone pain associated with diverse skeletal abnormalities.HypothesisCanine OS cells actively produce nociceptive ligands with the capacity to directly or indirectly activate peripheral pain receptors residing in the bone tumor microenvironment.AnimalsTen dogs with appendicular OS.MethodsExpression of nerve growth factor, endothelin‐1, and microsomal prostaglandin E synthase‐1 was characterized in OS cell lines and naturally occurring OS samples. In 10 dogs with OS, circulating concentrations of nociceptive ligands were quantified and correlated with subjective pain scores and tumor volume in patients treated with standardized palliative therapies.ResultsCanine OS cells express and secrete nerve growth factor, endothelin‐1, and prostaglandin E2. Naturally occurring OS samples uniformly express nociceptive ligands. In a subset of OS‐bearing dogs, circulating nociceptive ligand concentrations were detectable but failed to correlate with pain status. Localized foci of nerve terminal proliferation were identified in a minority of primary bone tumor samples.Conclusions and Clinical ImportanceCanine OS cells express nociceptive ligands, potentially permitting active participation of OS cells in the generation of malignant bone pain. Specific inhibitors of nociceptive ligand signaling pathways might improve pain control in dogs with OS.

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Section: Discussionmentioning

confidence: 98%

Expression of Nociceptive Ligands in Canine Osteosarcoma

Shor

Fadl-Alla

Pondenis

et al. 2015

Veterinary Internal Medicne

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“…In some studies, atrasentan also reduced bone pain, consistent with a potential role for ET-1 in nociception. 35 A recently published Phase II study on the ETA-selective antagonist ZD4054 in patients with mildly symptomatic bone metastases and castrate-resistant prostate cancer also did not affect time to progression, but did significantly improve overall survival. 36 The basis for these seemingly discrepant findings remains unknown.…”

Section: Resultsmentioning

confidence: 99%

Bone-specific growth inhibition of prostate cancer metastasis by Atrasentan

Drake

Danke

Henry

2010

Cancer Biology & Therapy

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“…In the latter experiments, ET-1 axis inhibition both with small-molecule inhibitors resulted in significant pain control. ET-1 -mediated enhancement of pain responses in a prostate cancer inoculation -induced pain model is mediated through ET A , and this effect is reversed by selective ET A inhibition (28). Recently, a compensatory analgesic action has been proposed, which is initiated by ET-1 on binding to ET B and is mediated through the release of h-endorphin (29).…”

Section: Ets and Their Receptorsmentioning

confidence: 99%

Targeting Bone Metastasis in Prostate Cancer with Endothelin Receptor Antagonists

Carducci

Jimeno

2006

Clinical Cancer Research

127

103

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Recent advances in the understanding of prostate cancer biology and its progression to bone metastasis have led to the development of drugs directed against precise molecular alterations in the prostate tumor cell and host cells in the normal bone environment such as osteoclasts and osteoblasts. Endothelins (ETs) and their receptors have emerged as a potential target in prostate cancer bone metastasis. By activating the ET A receptor, ET-1is pathogenically involved in facilitating several aspects of prostate cancer progression, including proliferation, escape from apoptosis, invasion, and new bone formation, processes that are general to many malignancies. Notwithstanding, there are a number of features specifically driven by the ET axis in prostate cancer, such as creating and perpetuating a unique interaction between the metastatic prostate cancer cell and the bone microenvironment (osteoblast, osteoclast, and stroma) or altering the equilibrium in pain modulation. These features have led to the preferential clinical evaluation of atrasentan (ABT-627) as a biological therapy in prostate carcinoma, first in hormone-refractory prostate cancer. Biological activity of atrasentan in patients with prostate cancer has been shown by the suppression of biochemical markers of prostate cancer progression in bone, and clinical activity is evidenced by a consistent trend demonstrating a delay in time to disease progression when compared with placebo, especially in patients with bone metastases. Further studies of atrasentan and other selective ET-1antagonists (ZD4054) are ongoing.Recent advances in the understanding of prostate cancer biology and its progression to bone metastasis have led to the development of drugs directed against precise molecular alterations in the prostate tumor cell and host cells in the normal bone environment such as osteoclasts and osteoblasts. Targeting specific pathways to stop cancer growth is generally less toxic to normal cells and improves tolerability, and thus anticancer drug discovery has shifted from an empirical random screening approach to a more rational and mechanistic, target-directed approach, where specific abnormalities in cell functioning are modulated in a classic drug-receptor fashion (1). Endothelins (ETs) and their receptors have emerged as a potential target in prostate cancer bone metastasis and is the focus of this review. ETs and Their ReceptorsThe ETs constitute a family of three 21-amino-acid peptides (ET-1, ET-2, and ET-2) that are synthesized as propeptides and are transformed to their active forms by sequential endopeptidase-and ET-converting enzyme-mediated cleavage. ET-1 is the most common circulating form of ET and has a median half-life of 7 minutes (2). It is cleared by a double mechanism that consists in ET receptor B (ET B ) -mediated uptake and degradation by neutral endopeptidase (3). Each of the three ETs has a unique pattern of distribution; ET-1 is not organ specific and is expressed primarily by endothelial cells, whereas ET-2 is mainly presen...

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Effects of selective endothelin ET A receptor antagonists on endothelin-1-induced potentiation of cancer pain

Cited by 38 publications

References 26 publications

Expression of Nociceptive Ligands in Canine Osteosarcoma

Expression of Nociceptive Ligands in Canine Osteosarcoma

Bone-specific growth inhibition of prostate cancer metastasis by Atrasentan

Targeting Bone Metastasis in Prostate Cancer with Endothelin Receptor Antagonists

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