Antidepressants and risk of cancer: a case of misguided associations and priorities.
Antidepressants and risk of cancer: a case of misguided associations and priorities.
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抗抑郁药和癌症风险：误导性关联和优先事项的案例。
DOI：
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发表时间：
2003
影响因子：
2.9
通讯作者：
A. Konstantinidou
中科院分区：
文献类型：
--
作者：
T. Theoharides;A. Konstantinidou
选择性5-羟色胺再摄取抑制剂（SSRI）氟西汀、帕罗西汀和西酞普兰在体外抑制Burkitt淋巴瘤细胞凋亡; 1这些抗抑郁药物被认为在有效性上相似，并且可以增加5-羟色胺的突触水平，对其他神经递质的影响很小。2这不是受体拮抗作用，但是阻止了5-羟色胺的再摄取，而5-羟色胺的再摄取干扰了细胞凋亡，而细胞凋亡是由胡萝卜素促进的。5-羟色胺转运体（SERT）。1鉴于缺乏5-羟色胺氧化代谢物和单胺氧化酶抑制剂无法逆转马诺宁诱导的细胞凋亡，作者认为SERT本身在与5-羟色胺结合时以某种方式驱动细胞凋亡。然而，这些体外结果需要全身无法达到的血清素浓度，除了类癌或肺cariroma异位血清素分泌的情况;3然而，在这种情况下，血清素似乎不会对肿瘤生长产生不利影响。在之前的两项临床研究中，有报道称，服用帕罗西汀的女性患乳腺癌的风险增加了7倍;那些服用较老的三环类抗抑郁药的人，增加血清素和去甲肾上腺素的水平，以及拮抗组胺-1受体，风险高出2倍。4然而，在该年的随后报告中，同样的作者宣布帕罗西汀仅与70%的风险增加相关，而不是先前报道的7倍或700%。5这样的信息在抗抑郁药的使用上造成了相当大的混乱，特别是在癌症患者中。抗抑郁药在实验室试验中曾被报道可促进某些肿瘤的生长，6、7沿着某些抗组胺药。8在这些报告中，阿米替林和氟西汀，沿着组胺-1受体拮抗剂氯雷他定、仅低剂量的阿司咪唑和羟嗪，可增加小鼠黑色素瘤的生长;然而，高剂量则不然。9，10其他研究表明阿米替林和地昔帕明可能会增加患乳腺癌的风险。11 -13然而，有一个无法解释的矛盾现象，即许多出版物报告了相反的结果。例如，羟嗪被证明对人乳腺癌细胞具有细胞毒性14，而其他组胺-1受体拮抗剂对肿瘤细胞增殖具有保护作用15。此外，氟西汀、丙咪嗪和西酞普兰表现出抗肿瘤特性16，阿米替林在其他地方抑制肾细胞腺癌的生长。氟西汀和帕罗西汀都被发现保护神经元免受压力的破坏作用。18据报道，组胺通过刺激细胞分裂和激活抑制性T细胞而促进癌症。19，20种具有组胺-1受体拮抗剂作用的药物
the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, paroxetine and citalopram prevented apoptosis of Burkitt lymphoma cells in vitro;1 These antidepressant drugs are considered similar in effectiveness and act to increase synaptic levels of serotonin, with minimal effects on other neurotransmitters.2 It was not receptor antagonism, but prevention of serotonin reuptake that interfered with apoptosis that was otherwise promoted by serotonin.1 The authors reached the tentative conclusion that the action of serotonin was mediated through the serotonin transporter (SERT).1 In view of the lack of serotonin oxidative metabolites and the inability to reverse serotonininduced apoptosis by monoamine oxidase inhibitors, the authors suggested that SERT, itself, somehow drives apoptosis upon binding to serotonin. However, these in vitro results required serotonin concentrations that are unattainable systemically, except in cases of carcinoid or lung cariroma ectopic serotonin secretion;3 yet, in such cases, serotonin does not appear to adversely affect tumor growth. In two previous clinical studies, it was reported that women taking paroxetine had a 7-fold increased risk of breast cancer; those taking the older tricyclic antidepressants, that increase levels of both serotonin and norepinephrine, as well as antagonize histamine-1 receptors, had a 2-fold higher risk.4 However, in a subsequent report within that year, the same authors announced that paroxetine was associated with an increased risk of only 70%, instead of the 7-fold or 700% reported previously.5 Such information has created considerable confusion over the use of antidepressants, especially in cancer patients. Antidepressants had previously been reported to promote the growth of some tumors in laboratory tests,6,7 along with certain antihistamines.8 In those reports, amitriptyline and fluoxetine, along with the histamine-1 receptor antagonists loratadine, astemizole only in low doses and hydroxyzine, increased melanoma growth in mice; however, high doses did not.9,10 Other studies suggested that amitriptyline and desipramine may increase the risk of breast cancer.11–13 Yet, there is an unexplained paradox in that many publications report opposite results. For instance, hydroxyzine was shown to be cytotoxic against human breast cancer cells14 and other histamine-1 receptor antagonists were protective against tumor cell proliferation.15 Moreover, fluoxetine, imipramine and citalopram demonstrated antineoplastic properties16, elsewhere amitriptyline inhibited the growth of renal cell adenocarcinoma.17 In fact, amitriptyline, fluoxetine and paroxetine were all found to protect neurons from the damaging effects of stress.18 Histamine has been reported to promote cancer by stimulating cell division and activating suppressor T-cells.19,20 Drugs with histamine-1 receptor antagonist actions GUEST EDITORIAL
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DOI：
10.1056/nejm199301283280408
发表时间：
1993-01
期刊：
The New England journal of medicine
影响因子：
--
作者：
S. Galli
通讯作者：
S. Galli
影响因子：
5
作者：
LINKINS, RW;COMSTOCK, GW
通讯作者：
COMSTOCK, GW
DOI：
--
发表时间：
1992-11
期刊：
The American journal of pathology
影响因子：
--
作者：
Ruo-dan Zhang;J. Price;T. Fujimaki;C. Bucana;I. Fidler
通讯作者：
Ruo-dan Zhang;J. Price;T. Fujimaki;C. Bucana;I. Fidler
DOI：
10.1073/pnas.79.16.5052
发表时间：
1982-08
影响因子：
11.1
作者：
J. Siegel;A. Schwartz;P. Askenase;R. Gershon
通讯作者：
J. Siegel;A. Schwartz;P. Askenase;R. Gershon
使用伽马相机检测大鼠脑中 99 锝-葡萄糖外渗，对血脑屏障 (BBB) 渗透性进行无创评估。
DOI：
10.1016/s1385-299x(01)00104-0
发表时间：
2001
期刊：
Brain research. Brain research protocols.
影响因子：
--
作者：
Esposito,P;Jacobson,S;Connolly,R;Gheorghe,D;Theoharides,TC
通讯作者：
Theoharides,TC