有机稀土化合物对SOS反应的抑制作用

本文应用ＳＯＳ显色法研究了三种有机稀土化合物及其相应螯合剂的抗诱变作用。抗坏血酸稀土、拧橡酸稀土及二胺四乙酸稀土浓度分别在０．５￣１．５ｍｇ／ｍｌ、１￣２０ｍｇ／ｍｌ及５￣４０ｍｇ／ｍｌ时，对已知致癌物亚硝基胍和３，４－苯并芘诱导的ＳＯＳ反应具有抑制作用，且有较好的剂量效应关系。而单纯的螯合剂抗坏血酸 效果很好，柠檬酸显示微弱的抗诱变性，乙二胺四乙酸二钠则无抗诱变作用。     

氧化苦参碱对肿瘤诱导血管内皮细胞增殖的抑制作用

目的 探讨氧化苦参碱（Ｏｘｙ）对肺癌和胃癌细胞诱导血管内皮细胞（ＶＥＣ）增殖的抑制作用。方法 用ＭＴＴ法检测不同浓度Ｏｘｙ对ＶＥＣ、人肺腺癌ＳＰＣ－Ａ－１细胞、人低分化胃癌ＭＫＮ－４５细胞增殖及ＳＰＣ－Ａ－１和ＭＫＮ－４５细胞诱导ＶＥＣ增殖的抑制。结果 Ｏｘｙ浓度为２．５～１０ｍｇ／ｍｌ时,对ＶＥＣ增殖的抑制率为４．６％～３６．４％;Ｏｘｙ浓度为０．１５６～１０ｍｇ／ｍｌ时,对肺癌ＳＰＣ－Ａ－１和     

STUDY ON THE MUTAGENIC AND ANTIMUTAGENIC POTEN-TIALS OF GYPENOSIDES(GPS)IN MICE

对绞股蓝总皂甙（ＧＰＳ）的研究表明：急性毒性＞１０００Ｏｍｇ／ｋｇ，各项致突变试验结果均为阴性；在ＧＰＳ剂量为１０００、２５００，５００Ｏｍｇ／ｋｇ时由环磷酰胺所致小鼠骨髓细胞微核率分别为１１．９‰、８．５‰和１３．６‰均较环磷酰胺组的２９．９‰明显降低（Ｐ＜０．０５）。在５－５０μｇ／皿范围内，ＧＰＳ对ＴＡ９８、ＴＡ１００和ＴＡ１０２菌株经不同阳性物诱导后的菌落回变数有不同程度降低，对ＴＡ９８菌株在２－ＡＦ（Ｓ９＋）有良好的抗诱变作用，并呈剂量反应关系。结果提示，绞股蓝总皂甙在体内和体外均表现出明确的抗诱变作用。本文还对其抗诱变作用的可能机理进行了探讨。     

MUTAGENICANDANTIMUTAGENICDETECTIONOFSODIUMBISELENITEINVITRO

亚硒酸氢钠（ＮａＨＳｅＯ３）的致突变和抗突变作用尚无定论，本文应用稍加修改的ＳＯＳ／Ｕｍｕ显色试验对其这方面的作用作了研究。结果发现，ＮａＨＳｅＯ１剂量在０．６７－８．００ｍｇ／ｍｌ范围内，无Ｓ９时，ＳＯＳ反应的诱导率（Ｒ）有剂量一效应关系，最低诱导剂量为１．８６ｍｇ／ｍｌ：存在Ｓ９时，各剂量组的Ｒ值均接近于１。结果还揭示ＮａＨｓｅＯ３能明显抑制丝裂霉素Ｃ（ＭＭＣ）诱发的β－半乳糖苷酶（ＢＧａｓｅ）活性，其剂量－效应曲线呈抛物线。据此曲线的方程式，估得２０％、４０％和６０％抑制的剂量分别为０．４８，１．３７和３．２１ｍｇ／ｍｌ；最大有作用剂量为３．５８ｍｇ／ｍｌ，其抑制率为６１％，这些结果表明：ＮａＨＳｅＯ３可能是ＳＯＳ的直接诱导剂，同时又是ＭＭＣ诱发ＳＯＳ反应的强抑制刑，且可在无明显诱导作用的剂量（＜１．８６ｍｇ／ｍｌ）下，即可有抗ＭＭＣ的诱导作用。     

亚硒酸钠和维甲酸对MNNG诱导人全血白细胞非程序DNA合成的影响

本文应用非程序ＤＮＡ合成（ＵＤＳ）试验，观察了亚硒酸钠（Ｎａ２ＳｅＯ３）和维甲酸（ＲＡ）单独和联合作用对致癌物ＭＮＮＧ诱发的人全血白细胞ＤＮＡ损伤的影响。结果表明，Ｎａ２ＳｅＯ３和ＲＡ均具有抗诱变作用；当Ｎａ２ＳｅＯ３（０．１μｇ／ｍｌ）和ＲＡ（０．１μｇ／ｍｌ）联合作用时，也可明显降低ＭＮＮＧ诱发的ＵＤＳ值，其联合抑制作用大于Ｎａ２ＳｅＯ３的单独作用。实验结果还显示，Ｎａ２ＳｅＯ３作为抗癌剂，它在高剂量时又呈现遗传毒性。     

亚硒酸钠和叶绿酸抗致癌物诱发BALB／3T3细胞DNA非程序合成的研究

本文报道１０６～１０４ｍｏｌ／Ｌ亚硒酸钠（Ｎａ２ＳｅＯ３）和０．１ｍｇ～０．２ｍｇ／ｍｌ叶绿酸对致癌物Ｎ－甲基－Ｎ’－硝基－Ｎ－亚硝基胍（ＭＮＮＧ）和苯并［ａ］芘（ＢａＰ）诱发ＢＡＬＢ／３Ｔ３细胞ＤＮＡ非程序合成（ＵＤＳ）有明显的抑制作用（Ｐ＜０．０５～０．００１）。加致癌物前２４小时加入Ｎａ２ＳｅＯ３或叶绿酸，其抑制作用大于同时加入者（Ｐ＜０．０１～０．００１）。Ｎａ２ＳｅＯ３与叶绿酸联合作用比单独使用抑制作用更强（Ｐ＜０．００１）。加入超氧化物歧化酶（ＳＯＤ）抑制剂二乙基二硫代氨基甲酸钠能减弱叶绿酸对两种致癌物的抑制作用（Ｐ＜０．０１和＜０．０５），提示其作用机理可能与ＳＯＤ消除自由基有关。     

人胚胎提取液生物学活性研究及临床应用展望

本项研究证实从４～６．５个月的胎儿组织提取的有效成份（简称ＨＦＥ）具有多种生物学活性：可促进受照射损伤的小鼠造血功能的恢复，４项检测指标包括：①骨髓有核细胞数：实验组：６５．５±１５．８，对照组：１６．４±６．２。②外周血网织红细胞百分比Ｘ±ＳＤ，实验组：１６．６±０．６０，对照组０．２±０．０４。③ＣＦＵ－ＳＸ±ＳＤ，实验组：１９．６±９．６６，对照组：１．９±２．２８。④骨髓增生程度：实验组优于对照组。对５个肿瘤细胞株和正常人二倍体细胞株２ＢＳ均有不同程度的抑制生长作用，ＥＤ５０分别为Ｈｅｌａ：６２．５μｇ／ｍｌ，ＭＣＦ－７：７．８μｇ／ｍｌ，ＨＥＰ－２：４μｇ／ｍｌ，ＳＭＭＣ７７２１：６２．５μｇ／ｍｌ，Ｔｅａ：４．５μｇ／ｍｌ，而对ＬＡ－７９５和Ａ－５４９则有轻度刺激作用。可刺激人外周血单个核细胞增殖并与ＰＨＡ，ＩＬ－２有协同作用。对氨甲喋呤引起的大鼠肝、肺损伤有一定的保护治疗作用。本项研究将为其临床应用提供实验依据。     

重组人血管内皮抑素联合ＦＯＬＦＯＸ４方案治疗晚期大肠癌的临床观察

目的　评价重组人血管内皮抑素（恩度）联合ＦＯＬＦＯＸ４方案治疗晚期大肠癌的有效性和安全性。方法 经病理组织学检查确诊的晚期大肠癌患者１８例接受恩度联合ＦＯＬＦＯＸ４方案治疗。恩度１５ｍｇ加生理盐水５００ｍｌ静脉缓慢滴注,ｄ１ ～ｄ１４,间歇７天,重复给药;ＦＯＬＦＯＸ４方案具体为：奥沙利铂（Ｌ-ＯＨＰ）８５ｍｇ／ｍ２,静脉滴入２ｈ,ｄ１;亚叶酸钙（ＣＦ）２００ｍｇ／ｍ２,静脉滴入２ｈ,氟尿嘧啶（５-ＦＵ）４００ｍｇ／ｍ２静脉推注后予以６００ｍｇ／ｍ２持续静脉滴入２２ｈ,ｄ１～ｄ２。每２周重复,２８天为１周期;３～４周期后评价疗效。结果　１８例患者均如期完成治疗,可评价客观疗效和安全性。获ＰＲ１１例,ＳＤ３例,ＰＤ４例,客观有效率为６１.１％（１１／１８）,疾病控制率为７７.８％（１４／１８）。主要毒副反应为骨髓抑制、消化道反应和周围神经毒性,无４级毒副反应,无心律失常及出血发生。结论　恩度联合ＦＯＬＦＯＸ４方案治疗晚期大肠癌具有协同作用,疗效好,毒性低,安全性好,值得临床进一步观察。     

非小细胞肺癌术后辅助化疗随机研究

目的评价非小细胞肺癌（ＮＳＣＬＣ）根治术后辅助化疗疗效。方法７０例Ⅰ～Ⅲ期ＮＳＣＬＣ患者在根治术后被随机分为两组。一组为辅助化疗组,于手术后３～４周开始接受辅助化疗：环磷酰胺３００ｍｇ／ｍ２;长春新碱１．４ｇ／ｍ２;阿霉素５０ｍｇ／ｍ２,第１天;顺铂２０ｍｇ／ｍ２,第１～５天;环己亚硝脲５０ｍｇ／ｍ２,第１天（ＣＯＡＰＣ方案）。每４～６周重复疗程,共４疗程。此后开始口服喃氟啶２００～３００ｍｇ,每天３次,连用１年或至肿瘤复发止。另一组为单纯手术组。结果辅助化疗组和手术组总的（Ⅰ～Ⅲ期）５年生存率分别为４８．６％和３１．４％,差异无显著性（Ｐ＞０．０５）;Ⅲ期病例的５年生存率分别为４４．０％和２０．８％,差异有显著性（Ｐ＜０．０２５）。Ⅰ～Ⅱ期病例分别为６０．０％和５４．５％（Ｐ＞０．７５）。结论ＮＳＣＬＣ根治术后辅助化疗,其５年生存率有一定提高,其中Ⅲ期病例的５年生存率,辅助化疗组优于单纯手术组。     

几个植物生长控制剂的磺胺类衍生物的细胞毒作用研究

用噻唑蓝还原法（ＭＴＴ法）试验了６个植物生长控制剂的磺胺类衍生物在１００μｇ／ｍｌ浓度下对人宫颈癌Ｈｅｌａ细胞生长的影响，其中二氯苯氧乙酰（２，４－Ｄ）与磺胺甲基异唑（ＳＭＺ）结合的衍生物对Ｈｅｌａ细胞生长抑制率为８８．７％，半数抑制浓（ＩＣ５０）为２８μｇ／ｍｌ；２，３，５－三氯苯甲酰－ＳＭ２的生长抑制率为８５．４％，ＩＣ５０为５８μｇ／ｍ１；２，３，５－三氯苯甲酰ＳＭＺ的抑制率为５４％。上述三种化合物对Ｈｅｌａ细胞显示细胞毒作用，而其他３种植物生长控制剂与磺胺或水杨酸甲酯形成的衍生物的生长抑制率均在５Ｏ％以下，未见明显细胞毒作用。     

中药蛇床子水溶性提取物中化学成分的抗诱变性研究

本文采用Ａｍｅｓ、体内试验小鼠骨髓细胞染色体畸变和骨髓多染红细胞微核试验,对蛇床子水溶性提取物中９种化学成分（蛇床子素,佛手柑内酯,异虎耳草素、欧芹属素乙、花椒毒酚,花椒毒素,甲基嘧啶,尿嘧啶和１种待定化合物）进行了抗诱变性研究。结果表明,蛇床子素,佛手柑内酯,异虎耳草素,欧芹属素乙,花椒毒酚和花椒毒素在典曲霉菌素Ｂ１诱变性的抑制作用中具有较高活性。蛇床子素,佛手柑内酯、异虎耳草素和欧芹属素乙在环     

Serum concentration of 5-FU and tegafur (FT-207) after administration of tegafur (FT-207) suppository with the colostomy

Tegafur (FT-207) suppositories were administered at a rate of 750 mg via the artificial anus (ST Group) following surgery of rectal cancer. Comparative studies were conducted of changes in blood concentrations of 5-FU and tegafur at the time of initial administration and following one week of continuous use for the low-anterior resection cases (LA Group) and the rectal administration cases (RE Group). FT-207 concentration at initial administration was low in the ST group compared to those for both LA and RE groups which received anal administration of the drug, but only little changes were noted. Blood concentration one hour after administration was 11.1 micrograms/ml, elevated to 14.3 micrograms/ml at two hours, and remained at 10 micrograms/ml and above for six hours following administration. The ST group 5-FU concentrations at two, four and six hours after administration were significantly lower than those in the RE group but the changes were little. Blood concentrations were 0.015 microgram/ml at one hour after administration, 0.017 micrograms/ml at two hours and maintained virtually the same level thereafter. An effective concentration of 0.012 microgram/ml was maintained even at ten hours following administration. After one week of administration of the suppositories, the ST group showed the lowest concentration among three groups, but it was approximately double compared to the initial concentration; FT-207 showed nearly the same concentration in the LA group and 5-FU blood concentration was 0.025 microgram/ml at one hour after administration, reached to a maximum of 0.030 microgram/ml at two hours and maintained 0.020 microgram/ml and higher at ten hours. 5-FU concentration in the LA and RE groups after one week of continuous administration showed a dual-peaked pattern. No patient with an abnormal artificial anus was involved in this study. The artificial anus is thought to be an adequate and effective administration route of FT-207 suppositories.     

Gemtuzumab ozogamicin-associated sinusoidal obstructive syndrome (SOS): an overview from the research on adverse drug events and reports (RADAR) project

Gemtuzumab ozogamicin (GO) was approved for marketing in 2000 by the United States Food and Drug Administration (FDA) for older patients with relapsed acute myeloid leukemia (AML). Four months later, 14 phase II clinical trial participants who received novel GO-containing combination chemotherapy regimens developed an unexpected hepatic toxicity termed sinusoidal obstructive syndrome (SOS) or hepatic veno-occlusive disease (VOD). Investigators associated with the Research on Adverse Drug Events and Reports (RADAR) project reviewed safety reports for GO included in reports of clinical trials and observational studies, interim reports from an FDA mandated Prospective Observational Registry, and the Food and Drug Administration's Adverse Event Reporting System. Medline searches provided incidence estimates of GO-associated SOS and comparative rates of SOS without GO. SOS is characterized by hyperbilirubinemia, painful hepatomegaly, ascites, and sudden weight gain developing at a median of 10 days following GO administration for patients who did not undergo an allogeneic SCT procedure and 13 days following an allogeneic SCT for patients who had previously received GO. Among adult AML patients who received GO in clinical trials, SOS incidence was 3% at doses < or =6 mg/m(2) if administered as monotherapy or in combination with non-hepatotoxic agents versus 28% if administered with thioguanine and 15% when administered as monotherapy at a dose of 9 mg/m(2). Observational studies identified SOS rates between 15% and 40% if an SCT is performed within 3 months of GO administration. The FDA mandated Prospective Observational Registry of patients who receive care at 60 medical centers has identified GO-associated SOS rates of 14% if an SCT is performed and 9% otherwise. Caution is advised when administering GO in routine clinical practice, particularly if administered with other hepatotoxic agents, at doses and schedules more intensive than those approved by the FDA, or within 3 months of a SCT procedure.     

用TK基因和HGPRT基因突变试验检测人参皂甙Re的抗诱变性

背景与目的： 用TK基因和HGPRT基因突变试验评价人参皂甙Re的抗诱变性,为其进一步的开发利用提供资料。 材料与方法： 设人参皂甙Re 12.5、25、50、100 μg/ml分别与致突变物甲基磺酸甲酯(MMS)5 μg/ml 同时处理TK6细胞的实验组,同时设溶剂对照组(1％ DMSO),阳性诱变对照组(MMS 5 μg/ml)和抗诱变阳性对照组(VitC＋MMS),各组处理TK细胞4 h后,采用微孔板法检测TK和HGPRT两个位点的突变频率。 结果： 随着剂量的增加,人参皂甙Re拮抗MMS诱变性的作用增大,表现在TK和HGPRT两个位点突变频率均较阳性诱变对照组降低,差异均具有统计学意义(P<0.05)。 结论： 人参皂甙Re具有拮抗MMS诱导的TK基因和HGPRT基因突变的作用;TK基因突变试验比HGPRT基因突变试验更为敏感。     

4 种水果的致突变及抗突变同步试验

 目的　为筛选有抗突变作用的天然水果。方法　采用抗突变和致突变同步快速试验对猕猴桃、石榴籽、冬雪蜜桃及野茄果 4种可食性水果进行了试验。做加和不加大鼠肝脏微粒体酶(S9)的两种试验。结果　全部受试物均未发现致突变毒性 ;猕猴桃及石榴籽显示对丝裂霉素C引起的致突变作用有拮抗效应 ;冬雪蜜桃有间接抗突变作用 ;野茄果未显示抗突变性。结论　猕猴桃、石榴籽及冬雪蜜桃是抗突变剂。     

42. The Report of Antimutagenicity and Mutagenicity of 7 Kinds NatrualEdible Plants and Vegetables

Purpose: With improvement of living standard, environmental quality become more and more seriously damaged. While the SOS bacterioplage induction methed is nearly a high-speed and reliable method to detect genetic toxins. The SOS syndronous test make an improvement on the above method. On the one hand, we are reducing the environmental pollution, on the other hand, we are attempt to find antimugens and some ways against cancer. Using the natrual edible plants against mutage and cancer is one of the important topic on preventing carcinogenic factors. The study examed 7 kinds natrual edible plants and vegetables. Method: We adopted the test of the Antimutagenicity and mutagenicity with S9 (rat liver microsomal enzymes system) and without S9 and repeat test. Result: The results showed all samples had no mutagenicity. Scallion seed, sweet potato and pomegranate peel were antimutagens against Mitomicy(MMC) with S9 and without S9. They are well worth of devoloping and using further. Pea seedling, crowndaisy chrysanthemum. alon and romaine had no antimutagenicity with and without S9. The people can eat usually.     

红景天提取物对顺铂致肾细胞毒性的保护作用

目的：研究红景天提取物（RE）对顺铂（DDP）诱导人胚肾细胞（HEK293）氧化损伤的保护作用。方法：体外培养HEK293细胞，将细胞分为对照组、不同浓度（0、0.5、1、2、4、8、16、32、64、128 mg/L）DDP组、不同浓度（0、0.25、0.5、1、2、4、8、16、32、64 mg/L）RE组和（2~16 mg/L）RE+20 mg/L DDP组。CCK-8法测定RE和DDP分别对HEK293细胞生长的影响，以及RE对DDP诱导细胞毒性的保护作用。二硫代二硝基苯甲酸法测定还原型谷胱甘肽（GSH）含量，硫代巴比妥酸法测定丙二醛（MDA）含量，黄嘌呤氧化酶法检测细胞超氧化物歧化酶（SOD）的活力。结果：与对照组比较，1~128 mg/L DDP导致细胞存活率显著降低（P < 0.01），且存在剂量-效应关系（r=0.85，P=0.002）；RE浓度在0.5~16 mg/L范围内细胞存活率逐渐升高（P < 0.01），但当RE浓度为64 mg/L时，可显著抑制HEK293细胞的生长（P < 0.01）；6~16 mg/L RE预处理后，对20 mg/L DDP所致细胞存活率的抑制有显著保护作用（与DDP组比较，P < 0.01）。与DDP组比较，RE能显著抑制DDP所致细胞内MDA含量的升高以及SOD活力和GSH含量的下降（P均 < 0.01）。结论：RE能提高HEK293细胞活力，并能拮抗DDP所致细胞氧化损伤，对DDP致肾细胞毒性具有明显的保护作用。     

Edta Clearance in Monitoring Cisplatin Dose Escalation in Patients with Bulky Metastatic Germ Cell Tumors of the Testis

A fast cisplatin clearance may reduce exposure time of tumor cells to the drug, and thus impair the expected effects of dose escalation. This hypothesis was tested in 23 patients with bulky metastatic germ cell tumors of the testis, treated with etoposide, bleomycin and high-dose cisplatin (60 mg/m²/24 h×4). The daily dose was retrospectively calculated in mg/1 EDTA clearance/24 h. A daily dose of 60 mg/m² of cisplatin in a person with a body surface of 1.7 m² and EDTA clearance of 100 ml/min was equivalent to 0.69 mg cisplatin/l EDTA clearance/24 h. In the whole group, 10 patients had complete remission (CR), 10 partial response (PR) and 3 progressive disease (PD). The mean daily cisplatin dose (×) in the whole group was 0.86 mg/1 EDTA clearance/24 h (range 0.35-2.00). For patients with CR, × × SD was 1.00±0.46, for those with PR 0.80±0.44, and for those with PD only 0.61±0.07. A cisplatin dose over 0.86 mg/1 EDTA clearance/24 h × 4 was obtained in 6/10 patients with CR versus 2/13 patients with PR + PD. Patients with PD received a significantly lower cisplatin dose than the whole group (0.61 versus 0.86 mg cisplatin/l EDTA clearance/24 h × 4.) The difference between the average toxicity grade after cisplatin dose over and below 0.69 mg/l EDTA clearance/24 h × 4 was significant only for leukocytes (WHO grade 2.17 versus 1.36). Thus, the effective escalated dose of cisplatin should preferably be calculated not per m² body surface but per 1 liter EDTA clearance. The 'ideal' escalated dose might be about 0.86-1.0 mg cisplatin/l EDTA clearance 24 h × 4.     

Effects of endocrine therapy on steroid-receptor content of breast cancer

In order to determine the mechanisms of relapse following response to endocrine therapy, we have measured the oestrogen receptor (RE) content of biopsies of breast cancer in patients receiving various types of endocrine treatment. RE content fell in responding (means of 260.2 to 12 fmol/mg protein) and in nonresponding (means of 155.1 to 31.8 fmol/mg protein) patients who had measurable receptor at the start of treatment. Some of these patients, and a further group of responders to endocrine therapy, were monitored until relapse. Tumour biopsies at the time of relapse showed that 10/14 tumour samples contained significant RE (mean of 86.7 fmol/mg protein; range less than 10-271 fmol/mg protein) after successful endocrine therapy. No relationship could be found between RE content and plasma gonadotrophin or steroid-hormone concentration, but the fall in RE content correlated with reduced numbers of tumour cells in the biopsy. These results indicate that relapse following successful endocrine therapy in breast cancer does not appear to be due to the emergence of RE-negative tumour cells. The fall in RE content during response to endocrine therapy may be due to reduced tumour-cell content of the biopsy.     

Autonomic proliferation of 2 distinct protein-free tumor-cell lines depends on the calmodulin pathway

Many oncogenes encode tyrosine kinases and the identification of appropriate inhibitors is an appealing proposition for the development of selective anticancer agents. These studies outline some screening models which we are currently developing in which we have evaluated a variety of compounds, reported to have tyrosine kinase inhibitory activity, as antitumor agents. In an enzyme based assay, using isolated pp60c-src, a variety of indolocabazoles, flavonoids, tyrophostins, herbimycin A and natural product cytotoxic agents were tested. Genistein, quercetin, staurosporine and herbimycin A were selected for comparison in whole cell studies. Soft agar colony formation of an activated c-src transformed NIH3T3 line was inhibited (IC50) by genistein (4.5 mug/ml) and quercetin (6.5 mug/ml) at similar concentrations and by herbimycin A (7 ng/ml) and staurosporine (1.3 ng/ml) at much lower concentrations. However, these agents inhibited colony formation of v-raf, H-ras and polyoma transformed NIH3T3 lines at comparable concentrations suggesting no selective inhibition of the src mediated transformation was being produced. Furthermore, quercetin failed to inhibit tyrosine phosphorylation of cellular proteins at concentrations shown to inhibit colony formation. Nevertheless. daily quercetin treatment (ip) for seven days at 1000 and 500 mg/kg/day did produce a meaningful increase in median survival time of athymic mice inoculated ip with 106 c-src transformed NIH3T3 cells. The screening models described are now being used to identify and develop new tyrosine kinase inhibitors from natural products and assess their potential as antitumor agents.