Abstract
The role of substance P in adverse pulmonary reactions induced by an anticancer agent paclitaxel was investigated in rats and humans who undertook post-operative chemotherapy for ovarian cancer. In rats, paclitaxel caused a marked plasma extravasation and edema in lungs with a concomitant decrease in arterial partial oxygen pressure, which were reversed by an NK1 antagonist LY303870. Substance P level in rat plasma and bronchoalveolar lavage fluid increased after paclitaxel injection. In 13 patients, plasma level of substance P but not histamine significantly (P < 0.05) increased during paclitaxel infusion. Therefore, substance P rather than histamine may be involved in paclitaxel hypersensitivity.
MeSH terms
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Animals
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Antineoplastic Agents / administration & dosage
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Antineoplastic Agents / adverse effects*
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Antineoplastic Agents / therapeutic use
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Bronchoalveolar Lavage Fluid / chemistry
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Female
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Histamine / blood
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Humans
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Hypersensitivity / blood
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Hypersensitivity / complications
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Hypersensitivity / physiopathology*
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Indoles / pharmacology
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Male
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Neurokinin-1 Receptor Antagonists
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Ovarian Neoplasms / blood
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Ovarian Neoplasms / complications
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Ovarian Neoplasms / drug therapy
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Ovarian Neoplasms / pathology
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Paclitaxel / administration & dosage
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Paclitaxel / adverse effects*
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Paclitaxel / therapeutic use
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Piperidines / pharmacology
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Rats
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Rats, Sprague-Dawley
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Respiratory Distress Syndrome / blood
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Respiratory Distress Syndrome / chemically induced
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Retrospective Studies
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Substance P / analysis
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Substance P / blood
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Substance P / metabolism*
Substances
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1-(N-(2-methoxybenzyl)acetylamino)-3-(1H-indol-3-yl)-2-(N-(2-(4-(piperidin-1-yl)piperidin-1-yl)acetyl)amino)propane
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Antineoplastic Agents
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Indoles
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Neurokinin-1 Receptor Antagonists
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Piperidines
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Substance P
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Histamine
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Paclitaxel