Inhibition of aberrant crypt growth by non‐steroidal anti‐inflammatory agents and differentiation agents in the rat colon

Inhibition of aberrant crypt growth by non‐steroidal anti‐inflammatory agents and differentiation agents in the rat colon
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非甾体抗炎药和分化剂对大鼠结肠异常隐窝生长的抑制

DOI:
10.1002/ijc.2910600415
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发表时间:
1995
影响因子:
6.4
通讯作者:
M. Velasco
M. Velasco
中科院分区:
医学1区
文献类型:
--
作者:
M. Wargovich;Chi Dai Chen;C. Harris;Eileen Yang;M. Velasco

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异常隐窝是单个到多个结肠隐窝的聚集体,证明发育异常的标志,并且可能是结肠癌最早可检测的病理学病变。异常隐窝测定已在2种方案中开发。在一种方法中,当与致癌物同时施用时,测试推定的化学预防剂的抑制作用。在另一项研究中,本研究的目的是通过胃肠外注射结肠致癌物氧化偶氮甲烷(AOM)诱导F344大鼠出现异常隐窝,并允许其发展4周,此时在亚甲蓝染色的结肠中发现平均每个结肠有90 - 100个异常隐窝病灶。然后,在实验的第二个4周期间,允许异常隐窝进一步发展到每个结肠> 150个病灶的频率,此时观察到多个隐窝病灶。在此期间,我们测试了4种镇痛药和2种分化剂对异常隐窝生长和发育的抑制作用。我们发现非甾体抗炎药吡罗昔康、阿司匹林和布洛芬,但对乙酰氨基酚,在抑制异常隐窝形成或发展为多个异常隐窝病灶方面无效。然而,使用化学抑制剂13-顺式维甲酸(13-cRA)和4-羟基-苯维甲酰胺(4-HPR)(已知的分化剂)治疗确实抑制了异常隐窝病灶的扩张,其中13-cRA是更有效的药物。
Aberrant crypts are aggregates of single to multiple colonic crypts evidencing hallmarks of dysplasia and may be the earliest detectable pathological lesions for colon cancer. The aberrant crypt assay has been developed in 2 protocols. In one, putative chemoprevention agents are tested for inhibitory effects when administered concomitantly with a carcinogen. In the other, the objective of this study, aberrant crypts were induced in F344 rats by parenteral injection of the colon carcinogen azoxymeth‐ane (AOM) and allowed to develop for 4 weeks, when an average of 90‐100 aberrant crypt foci per colon were found in the methylene blue‐stained colon. Then, during the second 4 weeks of the experiment, aberrant crypts were allowed to further develop to a frequency of > 150 foci per colon, a time when multi‐crypt foci were observed. During this time we tested the inhibitory effects of 4 analgesic drugs and 2 differentiation agents for effects of aberrant crypt growth and development. We found the non‐steroidal anti‐inflammatory drugs piroxicam, aspirin and ibuprofen, but not acetaminophen, to be effective in suppressing aberrant crypt formation or the progression to foci of multiple aberrant crypts. Treatment with chemo‐suppressing agents 13‐cis‐retinoic acid (13‐cRA) and 4‐hydroxy‐phenretinamide (4‐HPR), known differentiating agents, however, did suppress expansion of aberrant crypt foci, with 13‐cRA being the much more potent agent.
氧化偶氮甲烷处理的 F344 大鼠的结肠异常隐窝已降低己糖胺酶活性。
DOI: --
发表时间: 1990
期刊: The American journal of pathology
影响因子: --
作者:
Pretlow,TP;O'Riordan,MA;Kolman,MF;Jurcisek,JA
通讯作者: Jurcisek,JA
在大鼠结肠肿瘤发展的不同阶段,膳食吡罗昔康(一种非甾体抗炎药)对结肠癌发生的剂量相关抑制作用。
DOI: --
发表时间: 1987
期刊: Cancer research
影响因子: 11.2
作者:
Reddy,BS;Maruyama,H;Kelloff,G
通讯作者: Kelloff,G
DOI: --
发表时间: 1992-10
期刊: Cancer research
影响因子: 11.2
作者:
L. Marnett
通讯作者: L. Marnett
DOI: --
发表时间: 1991-03
期刊: Cancer research
影响因子: 11.2
作者:
T. P. Pretlow;B. J. Barrow;VV. Scott Ashton;M. O'riordan;T. Pretlow;J. Jurcisek;T. Stellato
通讯作者: T. P. Pretlow;B. J. Barrow;VV. Scott Ashton;M. O'riordan;T. Pretlow;J. Jurcisek;T. Stellato