Tyrosine kinase inhibitor therapy prescribed for non-urologic diseases can modify PSA titers in urology patients
Tyrosine kinase inhibitor therapy prescribed for non-urologic diseases can modify PSA titers in urology patients
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用于非泌尿科疾病的酪氨酸激酶抑制剂治疗可以改变泌尿科患者的 PSA 滴度
DOI：
10.1002/pros.23730
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Hayward Simon W.
中科院分区：
文献类型：
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作者：
Sasaki Takeshi;Franco Omar E.;Ohishi Kohshi;Filipovich Yana;Ishii Kenichiro;Crawford Susan E.;Takahashi Naoto;Katayama Naoyuki;Sugimura Yoshiki;Hayward Simon W.
背景酪氨酸激酶抑制剂（tyrosine kinase inhibitors，TKI）伊马替尼（imatinib）和尼洛替尼（nilotinib）用于治疗慢性粒细胞白血病（chronic myelogenous leukemia，CML）。在3例监测泌尿系统疾病的CML患者中，我们观察到TKI治疗的转换影响了前列腺特异性抗原（PSA）滴度。泌尿科医生和其他医疗专业人员需要了解患者可能因其他适应症而接受的药物的潜在副作用，以改变这一重要的前列腺疾病指标。TKI可能会影响PSA滴度独立的前列腺生长或volume.Materials和MethodsWe遵循PSA水平在泌尿科患者谁也接受TKI治疗慢性粒细胞白血病。我们确定了尼洛替尼和伊马替尼对增殖，AR和PSA表达的LNCaP和22 Rv1前列腺癌（PCa）细胞系使用真实的时间PCR和Western blotting.ResultsClinically的影响，尼洛替尼和达沙替尼可逆降低PSA滴度相比，伊马替尼。在高剂量下，尼洛替尼和伊马替尼都在PCa细胞中表现出抗增殖作用。在低剂量下，两种药物在mRNA和蛋白质水平上均降低了AR和PSA的表达。尼洛替尼发挥更大的影响，在较低的剂量比imatini.ConclusionsNilotinib下调血清PSA治疗非泌尿系适应症的患者，可能掩盖了临床有用的标志物，我们不能排除一个类似的，但较小的影响伊马替尼。尼洛替尼和伊马替尼均降低了PCa细胞系中的AR和PSA表达，尼洛替尼的作用在较低剂量下明显。泌尿科医生必须了解为其他疾病提供的药物对PSA滴度的影响，并意识到突然的变化可能并不反映潜在的前列腺疾病。
BackgroundThe tyrosine kinase inhibitors (TKI), imatinib and nilotinib, are used to treat chronic myelogenous leukemia (CML). In three CML patients being monitored for urologic diseases, we observed that switching of TKI therapy affected prostate‐specific antigen (PSA) titers. Urologists and other medical professionals need to be aware of the potential side‐effects of drugs that patients may be receiving for other indications to modify this important prostate diseases indicator. TKIs may affect PSA titers independent of prostate growth or volume.Materials and MethodsWe followed PSA levels in urology patients who were also undergoing TKI treatment for CML. We determined the effects of nilotinib and imatinib on proliferation, AR and PSA expression in the LNCaP and 22Rv1 prostate cancer (PCa) cell lines using real‐time PCR and Western blotting.ResultsClinically, nilotinib and dasatinib reversibly reduced PSA titers compared to imatinib. At high doses nilotinib and imatinib both demonstrated antiproliferative effects in the PCa cells. At low doses expression of AR and PSA was decreased by both drugs, at mRNA and protein levels. Nilotinib exerted greater effects at lower doses than imatinib.ConclusionsNilotinib down‐regulates serum PSA in patients being treated for non‐urological indications, potentially masking a clinical useful marker, we cannot exclude a similar but smaller effect of imatinib. Nilotinib and imatinib both decreased AR and PSA expression in PCa cell lines with the nilotinib effect evident at lower doses. Urologists must appreciate the effects of drugs provided for other diseases on PSA titers and be aware that sudden changes may not reflect underlying prostatic disease.