CN101027070A - 治疗和预防前列腺癌中的黄佩瑞任和鸡骨常山碱组合 - Google Patents
治疗和预防前列腺癌中的黄佩瑞任和鸡骨常山碱组合 Download PDFInfo
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Abstract
一种通过施用有效量的黄佩瑞任和鸡骨常山碱混合物而用于预防前列腺癌和/或降低PSA水平和/或减轻BPH(良性前列腺增生)或PIN(前列腺上皮内瘤形成)症状的方法和组合物。一种在具有表现出相对低的Gleason得分和非侵入性的、缓慢进展的前列腺癌的形态学特征的阳性组织活检的男性中,用于治疗低级前列腺癌和预防迁移性疾病的发作和/或减少PSA水平倍增时间的方法和组合物。黄佩瑞任和鸡骨常山碱可以以分别衍生于Pao Pereira和Rauwolfia Vomitora的天然提取物的形式。备选地,这两种活性化合物可以以纯化的形式施用。所述组合物可以与在治疗方案中应用的用法说明一起被包含在试剂盒中。
Description
发明领域
本发明属于前列腺癌预防和治疗的领域。更具体地,本发明涉及黄佩瑞任(Flavopereirine)和鸡骨常山碱组合在预防和治疗前列腺癌中的应用。
发明背景
前列腺癌是最常见的男性癌症。诊断是基于活组织切片检查,前列腺小切片的显微镜检。当活组织切片含有癌细胞时,治疗选择通常包括放射性和化学治疗,激素治疗以及外科手术移除前列腺。公知地,对于患者这些治疗经常是破坏性的,并且尽管这些治疗,前列腺癌的死亡率仍旧高居不下。
对于预防前列腺癌的进展的药剂存在紧急需求。事实上,在本国每年进行大约一百万前列腺的活组织切片检查,到目前为止大多数是阴性的。然而,这些男性遭受与升高的PSA水平相关的一定范围的症状和影响泌尿和性功能的良性前列腺增生的折磨。具有BPH(良性前列腺增生)或升高的PSA,或具有PIN(前列腺上皮内瘤形成),但是具有阴性的活组织切片的这一大组男性是处于癌症前期的:他们处于发展侵入性前列腺癌的高风险中,并且没有有效的预防治疗。在这一人群中预防或显著地延迟癌症发作的药剂具有显著的治疗价值。
另一大群男性被诊断患有前列腺癌,但是他们的活组织切片表现出所述疾病的低级形式。这一组处于公知的‘等待观察(watchful waiting)’或‘积极监视(active surveillance)’类别,并且当他们PSA水平的增加速率相对快速时,他们要经受上文提及的治疗干预。这一大组男性--处于等待观察的那些和具有更短的PSA倍增时间的那些,需要这样的药剂,即,抑制他们的癌症,减缓PSA增加的速率,并且防止他们癌症进展到更高的级别和更加侵入性的形式。这样的药剂将填补男性卫生保健的一个重要的空白。
第三群男性经受一种常规治疗,在这种情形中,他们的恢复通过监测他们的PSA水平变化速率或倍增时间来进行评估,PSA水平变化速率或倍增时间作为他们的癌症可能多么快速地复发的指示。有效地降低PSA水平和调节PSA倍增时间的药剂可以用来与常规治疗结合,以帮助预防前列腺癌的复发,因此显著地延长这一癌症患者群体的生命。
发明概述
本发明包括用于减轻和避免与前列腺癌相关的症状的发作,用于治疗低级前列腺癌和防止它们进展成为更加高级的癌症,以及用于降低PSA倍增时间并且因此预防或延缓转移性前列腺癌的组合物和方法。所述组合物包括黄佩瑞任和鸡骨常山碱的混合物。黄佩瑞任和鸡骨常山碱相对于彼此以定义的比例存在。所述黄佩瑞任和鸡骨常山碱可以作为植物提取物而存在。含有黄佩瑞任的提取物衍生于Pao Pereira,和含有鸡骨常山碱的提取物衍生于Rauwolfia Vomitora。黄佩瑞任提取物与鸡骨常山碱提取物的比例约为3-4∶1,并且是基于以提取物形式的活性成分,即,Pao Pereira提取物与Rauwolfia Vomitora提取物。备选地,黄佩瑞任和鸡骨常山碱可以以纯化的化学形式而存在,即,合成的黄佩瑞任和合成的鸡骨常山碱的组合。在活性成分是提取物形式的情形中,预计所述比例可以取决于活性组分的纯度而有些改变。所述量足以在前列腺癌细胞中诱导程序性细胞死亡和破坏细胞周期和DNA损伤应答途径。
预见了这种类型的化合物的任何常规施用模式。目前,口服施用是可考虑的。这种类型的典型模式将包括片剂和胶囊。这些将以试剂盒形式包装,具有书面的用法指导,以使治疗方案更容易。
预计用黄佩瑞任和鸡骨常山碱混合物治疗的群体分成3组:1)认为易感前列腺癌的那些受试者;2)患有具有低和高PSA倍增时间的低级形式的前列腺癌的那些受试者;和3)与传统药物治疗(特别是外科手术、放射性和冷冻和/或化学治疗)联合治疗的那些受试者。群体数目1可以包括高危组,诸如具有高PSA计数,BPH症状(良性前列腺增生)或患有PIN(前列腺上皮内瘤形成)的男性。这一组具有阴性的组织活检,并且将被认为是处于癌症前期。混合物的用量随着时间足以减轻BPH(良性前列腺增生)的症状,或降低升高的PSA水平。群体数目2应该已被诊断为患有前列腺癌并且因此可能具有阳性的组织活检,但是具有以更低的Gleason得分为特征的非侵入性(non-aggressive)肿瘤。这一群体将包括具有相对低的PSA增加速率的男性以及具有更高的PSA增加速率的男性。混合物的用量足以减缓前列腺癌向更侵入性阶段进展并且降低PSA水平和PSA倍增时间。群体数目3应该具有或将正在经受一些形式的前列腺癌治疗(外科手术、放射性、冷冻或化学治疗)。与这些治疗联合应用,混合物的用量足以降低PSA倍增时间。
本发明还包括这两种提取物以相对量的新组合,以预防前列腺癌或减轻BPH症状,特别是在癌症前期的男性中,包括诊断为患有前列腺上皮内瘤形成(PIN)的男性。所述提取物发挥有益作用,而没有通常与抗癌治疗相关的副作用。变成癌细胞的癌症前期细胞被所述混合物选择性地杀死,并且正常细胞不受影响。
本发明还包括在具有前列腺癌的癌症前期前体、升高的PSA、和良性前列腺增生,但是还没有患有前列腺癌的患者中预防前列腺癌发生的方法。本发明还包括用于减少PSA水平和/或减轻BPH症状的方法。
本发明还包括治疗患有局部(非迁移性的)前列腺癌的男性的方法,以预防更高级肿瘤和更加侵入性疾病的发展。癌症细胞被所述混合物选择性地杀死,并且正常细胞不受影响。
本发明还包括治疗具有长和短的PSA倍增时间的男性并且延长PSA倍增时间的方法。本发明将帮助维持具有长PSA倍增时间的男性的‘等待观察’状况,并且帮助预防具有短PSA倍增时间的男性更加侵入性或迁移性疾病的发作。
本发明还提供给个体施用以胶囊或片剂形式的口服有效剂量的提取物的方法。
本发明提供用于阻抑或抑制前列腺癌发生、PSA水平减少、和BPH症状减轻的方法,其通过施用由衍生于Pao Pereira和Rauwolfia Vomitora的天然提取物的组合组成的预防性药剂而实现。
本发明提供预防性药剂通过在癌细胞中诱导细胞程序性死亡和细胞周期和DNA损伤应答途径分裂的作用机制。在最理想的浓度,这种机制对癌细胞是选择性的,并且它还提供所述预防性药剂在降低PSA水平和BPH症状中的功效。
附图简述
图1显示在用Rauwolfia和Pao提取物治疗后LNCaP细胞生长分析的结果。
图2显示根据PARP分解和胱天蛋白酶-3活性,在LNCaP细胞中通过Rauwolfia和Pao提取物处理24小时后诱导的细胞程序性死亡。
图3显示通过FACS进行细胞周期分析。
图4(A和B)显示前列腺细胞瘤生长实验的结果。
图5显示TUNEL染色检测的结果。
图6显示TUNEL染色检测相应的统计数据。
图7显示阐明Rauwolfia对LNCap肿瘤异种移植物生长的抑制的实验结果。
发明详述
综述
本发明基于M.Beljanski的科学研究,他首次发展了这些提取物,并且在实验室实验和在动物研究中证明它们针对癌细胞的选择活性。Beljanski提供了这样的证据,即,这些化合物的毒性是基于它们与不稳定DNA之间的相互作用,他发现不稳定的DNA是癌细胞的基本特征。
本文所描述的工作支持前列腺细胞中DNA损伤的程度与前列腺癌的相互关系;这也支持前列腺癌症前期病况的具体诊断。本发明也描述了证明在前列腺癌细胞中包括细胞程序性死亡的诱导和细胞周期和DNA损伤应答途径的分裂的作用机制的工作。这在组织培养物和在动物异种移植物模型中显示。揭示黄佩瑞任和鸡骨常山碱的不同作用机制支持应用所述提取物的特殊组合以获得增强的治疗效果的观点。
前列腺DNA损伤的中间或癌症前期阶段的分类表明,这些化合物将特定地在处于向癌症状态转化的癌症前期细胞上行使它们的毒性作用,由此在高危险性男性中预防癌症,并且应答了非常大的患者群体的迫切需求。这些化合物还在癌细胞上行使它们的毒性作用,由此防止向更高级和更加侵入性形式的前列腺癌发展。
Pao Pereira和Rauwolfia Vomitora提取物抗癌作用的发现
按照美国专利号5,519,028中的流程制备来自Pao Pereira的提取物。按照欧洲专利号EP-A-0059817中的方法制备来自Rauwolfia Vomitora的提取物。这一方法包括从产物中消除有毒的化合物(例如,利血平)的部分纯化步骤。
首先在叫作致癌检测(Oncotest)的体外检测(U.S.Pat.No.4,264,729)中分析这两种提取物的生化活性。这一检测最初是设计成对于它们的致癌潜力而筛选化合物,并且是基于从癌细胞和从正常细胞分离的DNAs二级结构的差异(Beljanski,IRCSMed.Sci.1979.7:476)。当用作体外DNA合成的模板时,相对于纯化的正常DNA,纯化的癌细胞DNA表现出更大的chromicity(紫外光吸收)和更大的活性(Beljanski等,Expl.Cell.Biol.,1981.49:220-231)。这表明癌DNA双螺旋中的氢键被可再生地断裂,形成增加UV吸收和增强体外酶促活性的开口或环。结构上的这种基本的差异,癌DNA的更大的链分离特征,叫作DNA不稳定(Beljanski,Proceedings of theinternational seminar:Traditional Medicine:a Challenge to the 21st Century.1992.Oxford and IBH Publishing Co.)。
当将已知的致癌物质添加到致癌检测时,它们在用正常模板的DNA合成中促进少量的增加,但是在用癌症模板的DNA合成中促进高得多的增加(5-10倍)(Beljanski等.Third NCI-EORTC Symposium on new drugs incancer therapy.1981.Institut Bordet,Bruxelles)。认为这样的化合物通过进一步打开癌症DNA已经比较松散的结构而作用,由此增加酶对模板的接近,并且使得更多的DNA被合成。
当将Pao和Rauwolfia提取物用于致癌检测时,它们具有致癌物质相反的作用:chromicity减少并且从癌DNA模板合成DNA得到抑制(Beljanski,Expl.Cell.Biol.1982.50:79-87)。所述提取物的生化分析,包括DNA结合分析,鉴定了活性化合物为黄佩瑞任(在Pao Pereira中)和鸡骨常山碱(在Rauwolfia Vomitora中)。由于所述提取物和它们各自的化合物所表现出的抑制作用是对癌DNA特异的,由于对正常DNA没有作用,并且由于所筛选的几百中化合物中很少给出这些结果,所以对于它们作为抗癌药剂的潜力,进一步评估这些提取物和相应的活性化合物。
所述提取物经受长系列的检测,以检验它们对培养的癌细胞(Beljanski等.,IRCS Med.Sci.1984.12:587-588),对患有各种癌症的动物(Beljanski等.,Oncology,1986.43:198-203),和最终在众多人类病例研究中的作用。所述提取物表现出一些一致的和显著的特点。第一,在最适浓度,它们阻止在实验室中维持的癌细胞系的增殖,而不伤害健康的细胞。它们对小鼠的癌细胞是毒性的,但是对小鼠没有伤害。它们证明对一定范围的人类恶性肿瘤具有抗癌作用,但是没有表现出显著的副作用。这些提取物的活性是对癌DNA、癌细胞、和对患有癌症的生物体的肿瘤的选择性。存在这样的证据,即,这种选择性部分是由于在这些细胞外膜上发生的改变使得它们优先进入癌细胞(Beljanski等.International Journal of Oncology,1996.8:1143-1148)。在这些实验过程中,Pao Pereira提取物(黄佩瑞任)的活性(Beljanski,Genetics and Mol.Biol.,2000.23,1:29-33)和RauwolfiaVomitora提取物(鸡骨常山碱)的活性(未发表数据)显示出将人前列腺癌细胞系(PC3)的增殖抑制到相似的程度。由于它证明了混合物中的两种活性化合物针对如PC-3这样对激素没有反应的癌细胞有效,所以这一结果在本发明的上下文中是显著的。
对于致癌检测,从一定范围的癌组织和细胞,包括乳房、肺、卵巢、神经癌、埃利希腹水肿瘤细胞(Ehrlich ascites tumor cells),KB和Hela和L细胞,分离癌DNA。正常的DNA从健康的乳房、肺、卵巢、脑、初级肾(primary kidney)、培养液中的Vero细胞和SIRC细胞分离。暴露于Pao Pereira提取物的细胞系包括:u251,CCF-STTG-1 SW 1088和C6(脑);LoVo,CaCo-2(结肠);Sk-Hep 1(肝);A498(肾);G-36l(皮肤);Es 2,Sw 626(卵巢),ZR-75-1,MCF-7(乳房);MIA PaCa2(胰腺);PC3(前列腺);和TT(胸腺)。用Pao Pereira检测的正常细胞系包括CRL 1656(脑);CCD-18Co(结肠);Clone 9(肝);NRK-49F(肾);和CCD-97Sk(皮肤)。关于所述提取物用于治疗人癌症患者的应用的轶事信息的概述可以在Beljanski,Mirko Beljanski ou La Chronique d′une″Fatwa″Scientifique,2001,EVI Liberty Corp中找到。
癌细胞中的DNA不稳定性
应用傅立叶转化质谱的Malins等最近的研究(Cancer related changes inprostate DNA as men age and early identification of metastasis in primaryprostate tumors.Proc.Natl.Acad.Sci.2003 April 29100(9):5401-5406)已经表明,前列腺癌细胞中的DNA的确不同于正常前列腺细胞的DNA。Malins等将所述不同称为相对于正常DNA癌DNA紊乱的增加,并且这些变化与年龄和明显地与暴露于致癌物质有关。Malins等还能够可再现地检测到反应前列腺的癌症前期状况的疾病的过渡阶段(Malins等.Models of DNAstructure achieve almost perfect discrimination between normal prostate,benign prostatic hyperplasia(BPH),and adenocarcinoma and have a highpotential for predicting BPH and prostate cancer.Proc.Natl.Acad.Sci.1997January 7;94(1):259-264)。这种癌症前期状况似乎与已知为前列腺上皮内癌形成(PIN)的临床病况相对应。
Malins等报道致癌物质在前列腺中的存在引起物理性损伤DNA的自由基的产生,产生‘潜在地上十亿的改变的结构’。这些改变中有许多将影响稳定DNA双链的氢键。这可能在Beljanski报道的螺旋结构中产生开口。
支持Pao Pereira和Rauwolfia Vomitora提取物用于预防前列腺癌的应用的
新数据
1.细胞程序性死亡的诱导:黄佩瑞任作用的基本机制
黄佩瑞任和鸡骨常山碱是结构上相关的β-咔啉族生物碱。存在这样的证据,即,它们进入癌细胞中DNA相对开放的链,并且插入临近的核苷酸之间,它们的存在明显地干预了DNA的新陈代谢(Calvez,黄佩瑞任isan intercalating agent for non-supercoiled DNA,Cancer Detection andPrevention 1998;22(Supplement 1))。有效地,癌细胞不稳定的DNA是这些生物碱的靶点,并且最终结果是细胞死亡。在表明Pao和Rauwolfia提取物都在组织培养液中抑制LNCaP前列腺癌细胞的生长的新的实验中(图1),证实癌细胞的毒性。并且,这些提取物对LNCaP细胞表现出比对正常前列腺细胞的原代培养液显著更高的毒性(数据未显示)。
我们最近的实验也已经表明,黄佩瑞任的基本作用机制是诱导细胞程序性死亡,而鸡骨常山碱在这一途径的诱导中具有相对较小的作用。PaoPereira提取物和Rauwolfia Vomitora提取物都能在前列腺癌细胞系LNCaP中引发细胞程序性死亡,如由PARP分解和胱天蛋白酶-3的诱导所确定的那样[图2],但是Rauwolfia提取物的作用显著地低于Pao提取物的作用。
细胞程序性死亡--也叫作程序性细胞死亡--是一种引发细胞自杀的内在的生化途径。这一途径通常在发育过程中(例如,在神经系统的发育中)应用,通过免疫系统来保护机体免受改变细胞(例如,被病毒感染的细胞),并且作为对DNA损伤的细胞反应(例如,如果不破坏的话,这些细胞可能变成癌细胞)。在许多癌症中,包括许多前列腺癌,诱导细胞程序性死亡的机制是有缺陷的,因此应该正常自杀的细胞存活下来并且生长形成了肿瘤。许多癌症治疗实际上通过在某些类型的癌细胞中诱导细胞程序性死亡而其作用。
细胞程序性死亡的诱导是前列腺癌研究团体的中心主题,并且PaoPereira和(到显著更低的程度)Rauwolfia Vomitora提取物表现出这样的作用的事实使得它们极端有吸引力成为潜在的抗前列腺癌药剂。
2.基于对凋亡途径、对细胞周期和对DNA损伤应答途径的不同作用,黄佩瑞任和鸡骨常山碱协同作用的潜力
尽管两种提取物都诱导细胞程序性死亡,并且都对前列腺癌细胞有毒,通过荧光性激活的细胞分类分析它们在细胞周期中的作用揭示了不同的作用。如图3所示,Pao Pereira提取物引起LNCaP细胞在SubG0的累积,而Rauwolfia Vomitora阻碍细胞从G1到S期的进展。这一结果突出了所述两种提取物作用机制的不同,它们的生化本质尚未确定,尽管推测起来可能是基于黄佩瑞任和鸡骨常山碱物理结构的不同。一种可能是它们可以通过不同的途径(例如,p53-依赖型和p53-不依赖型)诱导细胞程序性死亡,并且另一种可能是它们可以以稍微不同的动力学而起作用。不管所述的原因,这种在活性上的不同具有治疗价值:这两种提取物的组合具有以互补方式作用的潜力,即,它们在它们的抗癌作用上潜在地是协同的。组合治疗经常用于癌症治疗,并且被广泛地认为提供比单独应用单一的抗癌药剂显著的优点。
为了进一步研究这两种提取物对前列腺癌细胞的作用,进行了一系列微点阵检测,其应用含有3套不同的人基因的阵列,所述人基因属于3种不同的生化途径:细胞程序性死亡,细胞周期,和DNA损伤。在每种情形中,用于所述检测的RNAs从已经暴露于所述提取物24小时的LNCaP细胞分离。从这些微点阵实验获得的数据全部在表I中提到。参见附件。注意,应用实时PCR来抽查在这些检测中观察到的变化的真实性。
尽管分析这些数据和综合Pao和Rauwolfia提取物对这些复杂的途径的作用的连贯描述的方法正在进行,并且将需要额外的实验,但是可以进行一些观察,以突出所述两种提取物在所有3种微点阵中诱导不同的反应的事实。例如,在DNA损伤反应点阵中,Pao提取物对14种基因(以粗体表示)的表达具有潜在地显著作用,而Rauwolfia提取物对30种转录物具有潜在地显著反应。更深入的检验揭示两种提取物对仅仅4种常见基因(ATM,DDIT3,ERCC1,和PDCD8)的表达具有显著作用。甚至更显著的是受这两种提取物影响的4种基因种仅有2种以相同的方式受到影响:DDIT3和ERCC1都是被增量调节。其它2种微点阵分析也揭示了PaoPereira和Rauwolfia Vomitora提取物的有分歧的结果,这强烈地证实这些提取物以组合方式应用以获得它们的互补作用。
3.在异种移植物动物模型中,黄佩瑞任和鸡骨常山碱是有抗前列腺癌肿瘤的活性
在无胸腺的小鼠(例如,Balb/c,nu/nu)中,人肿瘤长成异种移植物的能力为研究对人癌症治疗的生物反应提供了有用的体内模型。由于人肿瘤首次成功的异种移植到无胸腺的小鼠中,所以许多不同的人肿瘤细胞系(例如,乳腺,肺,泌尿生殖器,胃肠,头和颈,成胶质细胞瘤,骨,和恶性黑素瘤)已经被移植并且成功地在裸鼠中生长。这一系统的应用使得能够分析本发明的化合物在哺乳动物--一种用于人类的比基于细胞的检测更好的模型中,对LNCaP细胞前列腺癌异种移植体的活性。可以应用许多检测来确定所述化合物的活性、特异性和作用水平,并且在这种情形种,肿瘤体积和免疫组织化学是终点。
应用Pao Pereira提取物的异种移植物实验的结果的图表,具有肿瘤大小(立方毫米)针对时间(天数)作图的测量,在图4A中显示。与对照动物和与用50mg/kg每天治疗的动物相比较,Pao Pereira提取物10和20mg/kg的日常剂量在肿瘤体积上引起统计学显著的减少。图4B显示的对数转化清楚地表明所述结果分成两类。应用Rauwolfia Vomitora提取物的异种移植物实验的结果的图表在图7中显示。在这种情形中,相对于对照,所有3种剂量的提取物在肿瘤体积上引起统计学显著地减小[p<0.0001]。最后,来自应用从动物移除的肿瘤部分的2种免疫组织化学检测的数据证实Pao的作用机制是诱导剂量依赖性的细胞程序性死亡。TUNEL染色检测的结果在图5中显示,并且相对应的统计学数据在图6中显示。在BrdU染色检测中获得一致的结构[数据未显示]。对于RauwolfiaVomitora相似的免疫组织化学实验目前正在进行中。
这些提取物在减小肿瘤体积中的显著作用必须也被认为是根据在这些实验中动物的健康没有被任何不利的方式另外危及到的显著的事实。例如,治疗和对照小鼠的重量在整个实验过程中没有表现出显著的不同。两种提取物抗前列腺癌的作用以及不存在副作用为本发明中所描述的权利要求提供了强有力的科学基础。
配制和施用
黄佩瑞任和鸡骨常山碱组合可以作为药物组合物配制。所述组合物可以包含在药物试剂盒中。取决于要治疗的受试者,理想的施用模式,和治疗的类型--例如,防止,预防,治疗;黄佩瑞任和鸡骨常山碱组合以与这些参量一致的方式配制。这些技术的综述在Remington′s PharmaceuticalSciences,最新版本,Mack Publishing Co.,Easton,Pa.中找到。
一般而言,对于在治疗或预防中的应用,黄佩瑞任和鸡骨常山碱组合可以单独应用,或与其它化学治疗药剂化合物组合应用。黄佩瑞任和鸡骨常山碱的混合物可以单独施用或与其它药物活性成分组合施用,并且以单一的或多次施用。混合物制剂可以以适于全身施用的方式而配制。全身性制剂包括设计成注射的那些,例如,肌内,静脉内或皮下注射,或可以制备成经皮的,经粘膜的(transmucosl)或口服施用的。所述制剂通常包括稀释剂,以及,在一些情形中,佐剂,缓冲剂,防腐剂,等等。黄佩瑞任和鸡骨常山碱混合物还可以应用常规技术以脂质体组合物或作为微乳剂而施用。
如果口服施用,本发明的黄佩瑞任和鸡骨常山碱组合可以应用适宜的肠衣而在胃中免于降解。
用于本发明的混合物施用和配制的方式将取决于病况性质,病况严重性,要治疗的具体受试者,和执行医生的判断,配制将取决于施用的模式。由于本发明的混合物包括小分子,所以它便利地通过口服施用而施用,通过将它们与适当的药物赋形剂混合物以便提供片剂、胶囊、糖浆、等。口服施用的适宜的制剂还可以包括次要成分,诸如缓冲剂、调味剂等。典型地,制剂中活性成分的量将处于总制剂的1%-99%范围,但是取决于载体宽泛的变化是允许的。适宜的载体包括蔗糖、胶质、硬脂酸镁、乳糖、花生油、橄榄油、水等。
所述混合物还可以通过注射施用,包括静脉内、肌内、皮下或腹膜内注射。用于这样的应用的典型的制剂是在等渗载体中的液体制剂,诸如Hank′s溶液或Ringer′s溶液。
适当的备选制剂还包括脂质体制剂、缓慢释放制剂等。
可以应用任何适宜的制剂。在Remington′s Pharmaceutical Sciences,latest edition,Mack Publishing Company,Easton,Pa.中可以找到领域已知的制剂的纲要。参考这本手册是本领域的惯例。
本发明的化合物的剂量将取决于许多因素,其随患者和患者而变化。
口服剂量形式包括胶囊和片剂。胶囊或片剂可以容易地配制,并且可以制备成易于吞咽。片剂可以包含适当的载体、粘合剂、润滑剂、稀释剂、崩解剂、着色剂、调味剂、流动诱导剂、或熔融剂。片剂可以通过压缩或铸型而制备,任选地与一种或多种添加成分一起。压缩的片剂可以通过压缩以自由流动的形式(例如,粉剂、粒剂)的活性成分而制备,任选地与粘合剂(例如,明胶、羟丙基甲基纤维素)、润滑剂、惰性稀释剂、防腐剂、崩解剂(例如,甘醇酸淀粉钠、交联羧甲基纤维素)、表面活性剂或分散剂混合。适宜的粘合剂包括淀粉,明胶,天然糖,诸如葡萄糖或β-乳糖,玉米甜味剂,天然和合成的树脂,诸如阿拉伯树胶,黄芪胶,或藻酸钠,羧甲基纤维素,聚乙二醇,蜡,等。用于这些剂量形式的润滑剂包括油酸钠,硬脂酸钠,硬脂酸镁,苯甲酸钠,乙酸钠,氯化钠,等。崩解剂包括,例如,淀粉,甲基纤维素,琼脂,膨润土,黄原胶,等。铸型的片剂可以通过在适当的机器中将用惰性液体稀释剂润湿的粉碎的活性成分混合物定型而制备。
片剂可以任选地被包被或刻痕(scored),并且可以配制成提供活性成分的缓慢或可控制的释放。片剂还可以任选地以具有肠衣提供,以提供在肠部分而不是在胃中的释放。
如上文所述,黄佩瑞任和鸡骨常山碱混合物可以被包含在试剂盒形式中。所述混合物将被配制成用作药物。所述试剂盒可以包括一种或多种容器,其包含所述混合物的药物形式,所述混合物包括以单位剂量形式的治疗有效量的混合物。这样的试剂盒还可以包括,如果需要的话,一种或多种不同的常规药物试剂盒成分,诸如,例如,具有一种或多种药用载体的容器,附加的容器,等等,这对于本领域的技术人员是很容易显而易见的。用法指导,诸如打印的用法指导,例如,作为插入物或作为标签,标明要施用的成分的量的说明,施用指导,和/或与添加成分进一步混合的指导,也可以包含在试剂盒中。
表
方案 Pao Pereira细胞程序性死亡100μg/ml Pao 24hr/LNCaP
目录# Oligo GEAarray人细胞程序性死亡微点阵
密度 平均
Clover Clover关
阵列总数 2
总组数 2
背景 空白点:位置117,114,116
标准化 选择基因:位置126
点阵名称 C apoptosis light.GIF T apoptosis.GIF
分配组 组1 组2
*作为默认,组1被用作对照组。
位置 | UniGene | RefSeq# | 符号 | 组2 | 组1 | 组2/组1 |
1234567891011121314151617181920212223242526272829303132333435363738394041424344454647484950515253 | Hs.546292Hs.431048Hs.525622Hs.552567Hs.370254Hs.377484Hs.523309Hs.194726Hs.485139Hs.159428Hs.549082Hs.150749Hs.227817Hs.516966Hs.283672Hs 469658Hs.289052Hs.546359Hs.410026Hs.486542Hs.435556Hs.474150Hs.475055Hs.519374Hs.503704Hs.127799Hs.356076Hs.514527Hs.150107Hs.256126Hs.348263Hs.145726Hs.283454Hs.79428Hs.131226Hs.293753Hs.490366Hs.57973Hs.300355Hs.23248Hs.550529Hs.135201Hs.405153Hs.200242Hs.446146Hs.271815Hs.2490Hs.5353Hs.248226Hs.368982Hs.141125Hs.138378Hs.213327 | NM_002954NM_005157NM_005163NM_001160NM_004322NM_004323NM_004281NM_004874NM_001188NM_004324NM_003921NM_000633NM_004049NM_138578NM_020396NM_006538NM_052842NM_015367NM_004050NM_014739NM_016561NM_001196NM_001197NM_004536NM_001166NM_001165NM_001167NM_001168NM_016252NM_022161NM_033341NM_001205NM_004330NM_004052NM_004331NM_032515NM_004333NM_014550NM_032415NM_021209NM_024110NM_022162NM_006092NM_032587NM_014959NM_022352NM_033292NM_001230NM_012114NM_001224NM_004346NM_001225NM_004347 | RPS27AABL1AKT1APAF1BADBAG1BAG3BAG4BAK1BAXBCL10BCL2BCL2A1BCL2L1BCL2L10BCL2L11BCL2L12BCL2L13BCL2L2BCLAF1BFARBIDBIKBIRC1BIRC2BIRC3BIRC4BIRC5BIRC6BIRC7BIRC8BNIP1BNIP2BNIP3BNIP3LBOKBRAFCARD10CARD11CARD12CARD14CARD15CARD4CARD6CARD8CARD9CASP1CASP10CASP14CASP2CASP3CASP4CASP5 | 1.4620.1300.4940.0190.0240.0400.1370.0060.1870.0260.0160.0160.0120.0940.0130.0100.1240.1310.0150.0210.0040.1280.0310.0020.0460.0130.0060.6100.0080.0050.0110.0390.0161.0910.1390.0710.0140.0220.0050.0040.0080.0110.0070.0050.0020.0130.0120.0160.0110.1230.0160.1370.008 | 1.0290.2010.607-0.0030.0270.0840.117-0.0110.269-0.002-0.001-0.002-0.0070.139-0.009-0.0090.3250.2040.0010.029-0.0030.1290.006-0.0130.066-0.0120.0010.941-0.003-0.011-0.0120.0070.0100.9420.1630.0670.0010.003-0.000-0.015-0.0070.007-0.0080.003-0.001-0.004-0.004-0.006-0.0090.212-0.0030.189-0.003 | 1.4220.6480.814-6.0130.8960.4721.172-0.4910.695-16.620-27.393-8.129-1.8530.680-1.464-1.0460.3830.64225.0980.726-1.2840.9935.098-0.1740.698-1.1366.7770.648-2.277-0.441-0.9125.7281.5411.1590.8531.06413.0237.058-11.164-0.266-1.2581.576-0.7911.868-2.515-3.092-2.743-2.506-1.2730.581-4.9590.725-2.563 |
54555657585960616263646566676869707172737475767778798081828384858687888990919293949596979899100101102103104105106107 | Hs.3280Hs.9216Hs.369736Hs.329502Hs.390736Hs.249129Hs.448590Hs.38533Hs.380277Hs.237886Hs.484782Hs.133089Hs.86131Hs.80409Hs.248114Hs.87247Hs.20573Hs.36Hs.1116Hs.532826Hs.513667Hs.499094Hs 519842Hs.103755Hs.241570Hs.401745Hs.521456Hs.119684Hs.213467Hs.81791Hs.355899Hs.512898Hs.149168Hs.279594Hs.256278Hs.443577Hs.462529Hs.472860Hs.244139Hs.434878Hs.355307Hs.193418Hs.478275Hs.129708Hs.248197Hs.652Hs.2007Hs.501497Hs.494901Hs.1524Hs.408312Hs.523968Hs.192132Hs.137569 | NM_01226NM_001227NM_001228NM_001229NM_003879NM_001279NM_014430NM_003805NM_004938NM_014326NM_004401NM_004402NM_003824NM_001924NM_000514NM_003806NM_000875NM_000595NM_002342NM_021960NM_003946NM_013258NM_003804NM_003821NM_000594NM_003844NM_003842NM_003841NM_003840NM_002546NM_016639NM_003820NM_018647NM_001065NM_001066NM_014452NM_003790NM_001250NM_152877NM_003823NM_001242NM_001561NM_003810NM_003807NM_005092NM_000074NM_000639NM_001252NM_001244NM_003811NM_000546NM_005426NM_005427NM_003722 | CASP6CASP7CASP8CASP9CFLARCIDEACIDEBCRADDDAPK1DAPK2DFFADFFBFADDGADD45AGDNFHRKIGF1RLTALTBRMCL1NOL3PYCARDRIPK1RIPK2TNFTNFRSF10ATNFRSF10BTNFRSF10CTNFRSF10DNFRSF11BTNFRSF12ATNFRSF14TNFRSF19TNFRSF1ATNFRSF1BTNFRSF21TNFRSF25CD40FASTNFRSF6BTNFRSF7TNFRSF9TNFSF10TNFSF14TNFSF18CD40LGFASLGTNFSF7TNFSF8TNFSF9TP53TP53BP2TP73TP73L | 0.0200.030-0.0000.0490.0090.0130.0130.1150.0060.0210.0400.0400.1670.1770.0030.005-0.0020.0050.7860.4590.2460.0110.0050.0720.0040.0310.9850.0160.0060.0240.0200.0090.0030.1070.0060.0120.0320.0020.0060.0500.0060.0050.005-0.0010.0060.0030.0020.0030.0060.0030.0090.0070.0000.004 | 0.0120.027-0.0080.068-0.0050.0040.0090.1760.0010.0040.0250.0820.2410.1290.007-0.0040.0030.0040.7510.6050.3170.0050.0020.1490.0040.0230.9210.0080.007-0.0000.029-0.002-0.0050.180-0.001-0.0070.034-0.007-0.0090.082-0.0030.001-0.0020.001-0.002-0.005-0.0050.004-0.007-0.0040.0260.006-0.006-0.005 | 1.6961.1150.0270.725-1.6873.5231.4460.6526.2905.0611.5780.4900.6901.3770.431-1.276-0.7011.1051.0460.7580.7762.1282.2400.4850.8071.3761.0701.9910.927-67.9290.692-4.653-0.5150.595-4.329-1.6760.950-0.228-0.6730.613-2.1647.460-2.889-1.310-2.723-0.555-0.3680.754-0.823-0.6580.3681.239-0.073-0.808 |
108109110111112113114115116117118119120121122123124125126127128 | Hs.460996Hs.531251Hs.522506Hs.510528Hs.8375Hs.523930N/AN/AN/AN/AHs.544577Hs.534255Hs.509736Hs.509736Hs.520640Hs.520640N/AN/A | NM_003789NM_005658NM_021138NM_003300NM_004295NM_004619L08752N/AN/AN/ANM_002046NM_004048NM_007355NM_007355NM_001101NM_001101N/AN/A | TRADDTRAF1TRAF2TRAF3TRAF4TFAF5BlankPUC18BlankBlankAS1R2AS1R1AS1GAPDB2MHSPCBHSPCBACTBACTBBAS2CBAS2C | 0.2050.0020.0010.0260.434-0.0020.0010.0000.001-0.0020.0000.0040.0130.8780.6420.9750.9341.0081.0000.0550.751 | 0.246-0.0000.0160.0290.614-0.005-0.002-0.0020.0010.001-0.0070.002-0.0051.0140.6451.0061.0391.0301.0000.1060.922 | 0.835-5.2060.0780.8940.7070.356-0.346-0.2091.087-3.216-0.0161.532-2.9270.8660.9940.9690.8990.9791.0000.5170.815 |
方案 Rauwolfia细胞程序性死亡500μg/ml 24hr LNCaP
目录# Oligo GEAarray人细胞程序性死亡微点阵
密度 平均
Clover Clover关
阵列总数 2
总组数 2
背景 空白点:位置117,114,116
标准化 选择基因:位置1,121,123,124,125,126
点阵名称 Rauwolfia Apoptosis Rauwolfia Apoptosis Rx.GIF
分配组 组1 组2
*作为默认,组1被用作对照组。
位置 | UniGene | RefSeq# | 符号 | 组2 | 组1 | 组2/组1 |
123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354 | Hs.546292Hs.431048Hs.525622Hs.552567Hs.370254Hs.377484Hs.523309Hs.194726Hs.485139Hs.159428Hs.549082Hs.150749Hs.227817Hs.516966Hs.283672Hs.469658Hs.289052Hs.546359Hs.410026Hs.486542Hs.435556Hs.474150Hs.475055Hs.519374Hs.503704Hs.127799Hs.356076Hs.514527Hs.150107Hs.256126Hs.348263Hs.145726Hs.283454Hs.79428Hs.131226Hs.293753Hs.490366Hs.57973Hs.300355Hs.23248Hs.550529Hs.135201Hs.405153Hs.200242Hs.446146Hs.271815Hs.2490Hs.5353Hs.248226Hs.368982Hs.141125Hs.138378Hs.213327Hs.3280 | NM_002954NM_005157NM_005163NM_001160NM_004322NM_004323NM_004281NM_004874NM_001188NM_004324NM_003921NM_000633NM_004049NM_138578NM_020396NM_006538NM_052842NM_015367NM_004050NM_014739NM_016561NM_001196NM_001197NM_004536NM_001166NM_001165NM_001167NM_001168NM_016252NM_022161NM_033341NM_001205NM_004330NM_004052NM_004331NM_032515NM_004333NM_014550NM_032415NM_021209NM_024110NM_022162NM_006092NM_032587NM_014959NM_022352NM_033292NM_001230NM_012114NM_001224NM_004346NM_001225NM_004347NM_001226 | RPS27AABL1AKT1APAF1BADBAG1BAG3BAG4BAK1BAXBCL10BCL2BCL2A1BCL2L1BCL2L10BCL2L11BCL2L12BCL2L13BCL2L2BCLAF1BFARBIDBIKBIRC1BIRC2BIRC3BIRC4BIRC5BIRC6BIRC7BIRC8BNIP1BNIP2BNIP3BNIP3LBOKBRAFCARD10CARD11CARD12CARD14CARD15CARD4CARD6CARD8CARD9CASP1CASP10CASP14CASP2CASP3CASP4CASP5CASP6 | 0.4721-0.1908-0.03150.34420.0596-0.02720.0421-0.1620-0.0838-0.2322-0.1444-0.0527-0.0477-0.0831-0.0871-0.1348-0.0735-0.1448-0.17690.0460-0.0530-0.0215-0.1544-0.1686-0.0490-0.1521-0.1325-0.0861-0.1136-0.1444-0.1464-0.1315-0.01360.14150.00130.0394-0.0590-0.0769-0.0676-0.04970.00660.01330.06160.22820.14910.02120.03740.00460.03610.10270.12520.09240.0398-0.0096 | 0.4813-0.02980.1583-0.03760.06000.17090.12040.11700.09160.03430.03830.07060.08740.15770.11310.1165-0.00720.0797-0.01850.02720.07110.13730.10390.07480.02850.02510.07030.18530.06870.10630.08760.06610.03560.27960.09340.04170.06160.09600.08180.0446-0.00800.02460.0028-0.0227-0.00480.01830.10180.12860.00330.0795-0.0479-0.0382-0.0941-0.0607 | 0.98096.4113-0.1989-9.14430.9930-0.15900.3493-1.3841-0.9154-6.7676-3.7758-0.7466-0.5461-0.5271-0.7704-1.157210.2457-1.81549.57771.6914-0.7457-0.1569-1.4857-2.2556-1.7181-6.0525-1.8852-0.4648-1.6536-1.3592-1.6711-1.9900-0.38120.50590.01420.9461-0.9569-0.8004-0.8257-1.1153-0.83170.538721.9971-10.0675-30.96371.15890.36770.036110.85541.2920-2.6152-2.4217-0.42250.15811.94410.8059 |
555657585960616263646566676869707172737475767778798081828384858687888990919293949596979899100101102103104105106107108109 | Hs.9216Hs.369736Hs.329502Hs.390736Hs.249129Hs.448590Hs.38533Hs.380277Hs.237886Hs.484782Hs.133089Hs.86131Hs.80409Hs.248114Hs.87247Hs.20573Hs.36Hs.1116Hs.532826Hs.513667Hs.499094Hs.519842Hs.103755Hs.241570Hs.401745Hs.521456Hs.119684Hs.213467Hs.81791Hs.355899Hs.512898Hs.149168Hs.279594Hs.256278Hs.443577Hs.462529Hs.472860Hs.244139Hs.434878Hs.355307Hs.193418Hs.478275Hs.129708Hs.248197Hs.652Hs.2007Hs.501497Hs.494901Hs.1524Hs.408312Hs.523968Hs.192132Hs.137569Hs.460996Hs.531251 | NM_001227NM_001228NM_001229NM_003879NM_001279NM_014430NM_003805NM_004938NM_014326NM_004401NM_004402NM_003824NM_001924NM_000514NM_003806NM_000875NM_000595NM_002342NM_021960NM_003946NM_013258NM_003804NM_003821NM_000594NM_003844NM_003842NM_003841NM_003840NM_002546NM_016639NM_003820NM_018647NM_001065NM_001066NM_014452NM_003790NM_001250NM_152877NM_003823NM_001242NM_001561NM_003810NM_003807NM_005092NM_000074NM_000639NM_001252NM_001244NM_003811NM_000546NM_005426NM_005427NM_003722NM_003789NM_005658 | CASP7CASP8CASP9CFLARCIDEACIDEBCRADDDAPK1DAPK2DFFADFFBFADDGADD45AGDNFHRKIGF1RLTALTBRMCL1NOL3PYCARDRIPK1RIPK2TNFTNFRSF10ATNFRSF10BTNFRSF10CTNFRSF10DTNFRSF11BTNFRSF12ATNFRSF14TNFRSF19TNFRSF1ATNFRSF1BTNFRSF21TNFRSF25CD40FASTNFRSF6BTNFRSF7TNFRSF9TNFSF10TNFSF14TNFSF18CD40LGFASLGTNFSF7TNFSF8TNFSF9TP53TP53BP2TP73TP73LTRADDTRAF1 | 0.02480.04900.20670.14440.06330.15170.05830.01890.03880.09610.10200.25240.19410.1362-0.05600.0086-0.02050.06990.14240.10300.07290.00990.1348-0.0682-0.01420.20470.1375-0.02390.0331-0.0023-0.0212-0.02320.0199-0.04440.08510.04370.0179-0.0106-0.0480-0.0411-0.1070-0.07550.03580.03540.04570.1474-0.0212-0.0338-0.05170.00830.11590.05200.08550.0480-0.0133 | 0.01280.06080.01300.0028-0.0014-0.0411-0.0594-0.03210.02170.0776-0.0014-0.0384-0.0453-0.0652-0.0825-0.0573-0.01660.0950-0.0064-0.0206-0.0544-0.07130.0201-0.0844-0.04030.05820.0130-0.05920.0049-0.0119-0.0345-0.08700.02560.0002-0.0418-0.0689-0.0883-0.0886-0.0846-0.1004-0.0552-0.0221-0.0613-0.0707-0.03210.1443-0.06050.09000.03800.11100.0225-0.02950.04850.1010-0.0710 | 15.849051.5632-45.1769-3.6957-0.9809-0.58781.78541.2373-72.8507-6.5689-4.2895-2.08780.6782-0.15021.23490.7360-22.2920-5.0084-1.3386-0.13956.69680.80870.35383.517010.54060.40316.75800.19480.61470.26650.7750-253.5583-2.0347-0.6347-0.20250.11970.56750.40911.93723.4105-0.5839-0.5012-1.42301.02130.3505-0.3755-1.36030.07465.1539-1.76311.76240.47550.18670.81103.46530.1933-0.5788 |
110111112113114115116117118119120121122123124125126127128 | Hs.522506Hs.510528Hs.8375Hs.523930N/AN/AN/AN/AHs.544577Hs.534255Hs.509736Hs.509736Hs.520640Hs.520640N/AN/A | NM_021138NM_003300NM_004295NM_004619L08752N/AN/AN/ANM_002046NM_004048NM_007355NM_007355NM_001101NM_001101N/AN/A | TRAF2TRAF3TRAF4TRAF5BlankPUC18BlankBlankAS1R2AS1R1AS1GAPDB2MHSPCBHSPCBACTBACTBBAS2CBAS2C | -0.0288-0.12590.01490.01720.0500-0.0126-0.06360.0136-0.01290.26530.95840.70060.28390.99180.86861.57781.38902.10662.0996 | -0.0355-0.03630.0771-0.0298-0.0547-0.0463-0.00640.06110.13070.19740.89121.09970.10860.83950.86681.20421.50861.70551.6617 | -0.91430.27199.95360.2223-0.09891.34431.07540.63712.61341.18151.00211.31030.92081.23511.2635 |
方案 Pao细胞周期 100μg/ml 24hr LNCaP
目录# Oligo GEAarray人细胞周期微点阵
密度 平均
Clover Clover关
阵列总数 2
总组数 2
背景 空白点:位置117,114,116
标准化 选择基因:位置125
点阵名称 T cell cycle light.GIF T cell cycle light.GIF
分配组 组1 组2
*作为默认,组1被用作对照组。
位置 | UniGene | RefSeq# | 符号 | 组2 | 组1 | 组2/组1 |
1234567891011121314151617181920212223242526272829303132333435363738394041424344454647484950515253 | Hs.546292Hs.431048Hs.533262Hs.152173Hs.7101Hs.194695Hs.435561Hs.271791Hs.159428Hs.370292Hs.150749Hs.514527Hs.194143Hs.34012Hs.417050Hs.85137Hs.23960Hs.194698Hs.430646Hs.523852Hs.376071Hs.534307Hs.244723Hs.408658Hs.1973Hs.79101Hs.13291Hs.146607Hs.279906Hs.292754Hs.374127Hs.334562Hs.524947Hs.1634Hs.656Hs.514997Hs.160958Hs.474217Hs.405958Hs.533573Hs.19192Hs.95577Hs.500015Hs.158460Hs.435952Hs.20157Hs.119882Hs.184298Hs.382306Hs.370771Hs.238990Hs.106070Hs.421349 | NM_002954NM_005157NM_013366NM_013367NM_016237NM_004675NM_000051NM_001184NM_004324NM_016567NM_000633NM_001168NM_007294NM_000059NM_003914NM_001237NM_031966NM_004701NM_005190NM_053056NM_001759NM_001760NM_001238NM_004702NM_001761NM_004060NM_004354NM_001239NM_001240NM_001241NM_003903NM_001786NM_001255NM_001789NM_001790NM_004359NM_007065NM_003504NM_001254NM_003503NM_001798NM_000075NM_003885NM_003936NM_016408NM_176096NM_001259NM_001799NM_001260NM_000389NM_004064NM_000076NM_058195 | RPS27AABL1ANAPC2ANAPC4ANAPC5ARHIATMATRBAXBCC1PBCL2BIRC5BRCA1BRCA2CCNA1CCNA2CCNB1CCNB2CCNCCCND1CCND2CCND3CCNE1CCNE2CCNFCCNG1CCNG2CCNHCCNT1CCNT2CDC16CDC2CDC20CDC25ACDC25CCDC34CDC37CDC45LCDC6CDC7CDK2CDK4CDK5R1CDK5R2CDK5RAP1CDK5RAP3CDK6CDK7CDK8CDKN1ACDKN1BCDKN1CCDKN2A | 0.9920.0480.0100.0493.1180.0020.0290.0150.0070.0120.0040.2240.0060.0030.0020.0070.0480.0080.0130.0070.0000.3370.0420.0070.0020.0140.0570.2440.0040.0150.0830.0060.0620.0010.0080.0310.0200.0030.0070.0010.0450.7700.0040.0020.0060.0010.0030.0370.0220.9120.0410.0010.012 | 0.9560.0780.0090.1060.281-0.0000.0420.0310.0040.0200.0010.8060.0300.0000.0020.0140.1280.0040.0040.000-0.0000.8050.0800.0090.0010.0130.0980.691-0.0000.0130.1400.0040.362-0.0030.0210.0600.0150.0000.0090.0020.1370.957-0.002-0.0000.0100.0000.0010.0360.0030.8650.043-0.0020.026 | 1.0390.6221.0560.4670.422-6.3800.6820.4931.6590.6056.3470.2780.18235.6361.1770.4760.3711.9453.49316.573-2.7590.4190.5250.7743.6771.0330.5790.353-14.1181.1610.5941.3650.171-0.3070.3660.5161.33337.3460.7930.5690.3300.805-2.473-4.3460.5767.6385.7501.0368.1171.0540.956-0.4810.452 |
54555657585960616263646566676869707172737475767778798081828384858687888990919293949596979899100101102103104105106107108 | Hs.72901Hs.525324Hs.435051Hs.84113Hs.24529Hs.291363Hs.374378Hs.83758Hs.146806Hs.82919Hs.372286Hs.339735Hs.440320Hs.443960Hs.211463Hs.96055Hs.194333Hs.269408Hs.108371Hs.445758Hs.135465Hs.80409Hs.523510Hs.386189Hs.26663Hs.152983Hs.300559Hs.252712Hs.533185Hs.19400Hs.477481Hs.179565Hs.460184Hs.517582Hs.444118Hs.438720Hs.80976Hs.509523Hs.20555Hs.492208Hs.147433Hs.77783Hs.531879Hs.16184Hs.242635Hs.446554Hs.240457Hs.408528Hs.546282Hs.207745Hs.513609Hs.507866Hs.487540Hs.269898Hs.23348 | NM_004936NM_078626NM_001800NM_005192NM_001274NM_007194NM_001826NM_001827NM_003592NM_003591NM_003590NM_003589NM_003478NM_004399NM_004945NM_005225NM_004091NM_001949NM_001950NM_001951NM_001952NM_001924NM_005316NM_016426NM_016323NM_004507NM_014708NM_002266NM_002358NM_006341NM_004526NM_002388NM_005914NM_006739NM_005915NM_005916NM_002417NM_002431NM_005590NM_002485NM_182649NM_182687NM_002853NM_002873NM_005732NM_002875NM_004584NM_000321NM_002894NM_002895NM_005611NM_014059NM_002947NM_013376NM_005983 | CDKN2BCDKN2CCDKN2DCDKN3CHEK1CHEK2CKS1BCKS2CUL1CUL2CUL3CUL4ACUL5DDX11DNM2E2F1E2F2E2F3E2F4E2F5E2F6GADD45AGTF2H1GTSE1HERC5HUS1KNTC1KPNA2MAD2L1MAD2L2MCM2MCM3MCM4MCM5MCM6MCM7MK167MNAT1MRE11ANBS1PCNAPKMYT1RAD1RAD17RAD50RAD51RAD9ARB1RBBP8RBL1RBL2RGC32RPA3SERTAD1SKP2 | 0.0060.0210.0190.0250.0070.0020.0450.3300.3990.0100.0080.0430.0160.0080.0030.1000.0150.0040.0080.0080.0010.0750.0240.0060.0010.0040.0050.1800.0260.1180.3770.0070.0030.0090.0100.1420.0060.0030.0010.0030.5140.0290.0170.0060.0050.0030.0100.0320.0100.0080.0230.0050.0020.009-0.000 | 0.0050.0680.0450.0180.0020.0030.1230.6790.5380.0150.0000.0220.0020.0150.0020.2780.0450.0010.0040.000-0.0010.0320.0130.007-0.001-0.0000.0040.3460.0350.1540.5630.0070.0020.0160.0080.3450.0320.0020.0040.0020.7440.1440.0110.0010.001-0.0010.0200.0100.0110.0050.018-0.0030.0000.006-0.001 | 1.0940.3120.4241.4063.1010.5930.3690.4860.7430.66220.6791.9239.8000.5251.7620.3590.3225.0822.18098.497-0.7432.3101.8580.828-1.466-28.2001.2070.5200.7370.7670.6691.0252.1080.6001.2020.4110.1941.4060.3501.8340.6910.2011.5549.3844.031-2.6430.4893.1880.8901.4141.307-1.85428.1211.6650.039 |
109110111112113114115116117118119120121122123124125126127128 | Hs.81424Hs.79353Hs.379018Hs.408312Hs.406693N/AN/AN/AN/AHs.544577Hs.534255Hs.509736Hs.509736Hs.520640Hs.520640N/AN/A | NM_003352NM_007111NM_006286NM_000546NM_003334L08752N/AN/AN/ANM_002046NM_004048NM_007355NM_007355NM_001101NM_001101N/AN/A | SUMO1TFDP1TFDP2TP53UBE1BlankPUC18BlankBlankAS1R2AS1R1AS1GAPDB2MHSPCBHSPCBACTBACTBBAS2CBAS2C | 0.0270.0350.0080.0160.061-0.000-0.001-0.0000.0000.006-0.0000.0030.9110.3330.9810.9871.0000.9800.0320.669 | 0.0270.0380.0060.01B0.0440.001-0.001-0.0010.0010.0020.0040.0040.9900.4870.9170.9641.0000.9670.0930.841 | 1.0120.9011.3460.9141.381-0.2400.9110.1900.5553.958-0.1100.6270.9200.6841.0701.0241.0001.0130.3470.795 |
方案 Rauwolfia细胞周期 500μg/ml 24hr LNCaP
目录# Oligo GEAarray人细胞周期微点阵
密度 平均
Clover Clover关
阵列总数 2
总组数 2
背景 空白点:位置117,114,116
标准化 选择基因:位置1,121,122,123,124,125,126
点阵名称 Rauwolfia Rx Cell cycle.GIF
分配组 组1 组2
*作为默认,组1被用作对照组。
位置 | UniGene | RefSeq# | 符号 | 组2 | 组1 | 组2/组1 |
1234567891011121314151617181920212223242526272829303132333435363738394041424344454647484950515253 | Hs.546292Hs.431048Hs.533262Hs.152173Hs.7101Hs.194695Hs.435561Hs.271791Hs.159428Hs.370292Hs.150749Hs.514527Hs.194143Hs.34012Hs.417050Hs.85137Hs.23960Hs.194698Hs.430646Hs.523852Hs.376071Hs.534307Hs.244723Hs.408658Hs.1973Hs.79101Hs.13291Hs.146607Hs.279906Hs.292754Hs.374127Hs.334562Hs.524947Hs.1634Hs.656Hs.514997Hs.160958Hs.474217Hs.405958Hs.533573Hs.19192Hs.95577Hs.500015Hs.158460Hs.435952Hs.20157Hs.119882Hs.184298Hs.382306Hs.370771Hs.238990Hs.106070Hs.421349 | NM_002954NM_005157NM_013366NM_013367NM_016237NM_004675NM_000051NM_001184NM_004324NM_016567NM_000633NM_001168NM_007294NM_000059NM_003914NM_001237NM_031966NM_004701NM_005190NM_053056NM_001759NM_001760NM_001238NM_004702NM_001761NM_004060NM_004354NM_001239NM_001240NM_001241NM_003903NM_001786NM_001255NM_001789NM_001790NM_004359NM_007065NM_003504NM_001254NM_003503NM_001798NM_000075NM_003885NM_003936NM_016408NM_176096NM_001259NM_001799NM_001260NM_000389NM_004064NM_000076NM_058195 | RPS27AABL1ANAPC2ANAPC4ANAPC5ARHIATMATRBAXBCCIPBCL2BIRC5BRCA1BRCA2CCNA1CCNA2CCNB1CCNB2CCNCCCND1CCND2CCND3CCNE1CCNE2CCNFCCNG1CCNG2CCNHCCNT1CCNT2CDC16CDC2CDC20CDC25ACDC25CCDC34CDC37CDC45LCDC6CDC7CDK2CDK4CDK5R1CDK5R2CDK5RAP1CDK5RAP3CDK6CDK7CDK8CDKN1ACDKN1BCDKN1CCDKN2A | 0.97080.06170.31280.07850.00740.00920.57870.17670.04930.12290.11670.09960.12450.03280.27330.20590.06640.11240.08880.01360.00420.10370.11210.02410.08690.15590.09620.0272-0.05010.02850.1177-0.01910.11360.09620.06860.0282-0.0100-0.05010.0204-0.00850.21090.44820.14620.08690.07380.0742-0.02710.00550.10032.10990.15250.04930.0307 | 0.74100.09300.34050.0452-0.0339-0.09520.5695-0.00300.03810.03240.05520.19830.1423-0.0721-0.0522-0.02020.05200.04950.08340.6031-0.01520.1890-0.0053-0.02770.05090.11080.11490.1042-0.0081-0.0394-0.0072-0.04280.09480.11260.0795-0.0332-0.0202-0.1244-0.16190.00130.25000.71100.12590.0280-0.08460.02420.08110.02480.12910.49460.12840.02800.0098 | 1.31020.66410.91861.7375-0.2169-0.09691.0162-57.97431.29413.79652.11300.50240.8747-0.4555-5.2368-10.19731.27572.26901.06480.0225-0.28010.5487-21.0110-0.87011.70731.40700.83740.26156.2066-0.7230-16.42730.44501.19870.85440.8628-0.84800.49760.4029-0.1260-6.55660.84350.63041.16183.0991-0.87243.0702-0.33470.22100.77674.26621.18751.75823.1434 |
54555657585960616263646566676869707172737475767778798081828384858687888990919293949596979899100101102103104105106107108109 | Hs.72901Hs.525324Hs.435051Hs.84113Hs.24529Hs.291363Hs.374378Hs.83758Hs.146806Hs.82919Hs.372286Hs.339735Hs.440320Hs.443960Hs.211463Hs.96055Hs.194333Hs.269408Hs.108371Hs.445758Hs.135465Hs.80409Hs.523510Hs.386189Hs.26663Hs.152983Hs.300559Hs.252712Hs.533185Hs.19400Hs.477481Hs.179565Hs.460184Hs.517582Hs.444118Hs.438720Hs.80976Hs.509523Hs.20555Hs.492208Hs.147433Hs.77783Hs.531879Hs.16184Hs.242635Hs.446554Hs.240457Hs.408528Hs.546282Hs.207745Hs.513609Hs.507866Hs.487540Hs.269898Hs.23348Hs.81424 | NM_004936NM_078626NM_001800NM_005192NM_001274NM_007194NM_001826NM_001827NM_003592NM_003591NM_003590NM_003589NM_003478NM_004399NM_004945NM_005225NM_004091NM_001949NM_001950NM_001951NM_001952NM_001924NM_005316NM_016426NM_016323NM_004507NM_014708NM_002266NM_002358NM_006341NM_004526NM_002388NM_005914NM_006739NM_005915NM_005916NM_002417NM_002431NM_005590NM_002485NM_182649NM_182687NM_002853NM_002873NM_005732NM_002875NM_004584NM_000321NM_002894NM_002895NM_005611NM_014059NM_002947NM_013376NM_005983NM_003352 | CDKN2BCDKN2CCDKN2DCDKN3CHEK1CHEK2CKS1BCKS2CUL1CUL2CUL3CUL4ACUL5DDX11DNM2E2F1E2F2E2F3E2F4E2F5E2F6GADD45AGTF2H1GTSE1HERC5HUS1KNTC1KPNA2MAD2L1MAD2L2MCM2MCM3MCM4MCM5MCM6MCM7MK167MNAT1MRE11ANBS1PCNAPKMYT1RAD1RAD17RAD50RAD51RAD9ARB1RBBP8RBL1RBL2RGC32RPA3SERTAD1SKP2SUMO1 | 0.05150.12290.06390.06670.08630.12600.09780.11110.14220.17260.14470.12670.40510.13690.14560.13570.02440.13630.1388-0.02650.03160.14650.05150.08780.02070.09470.07480.00140.06080.01540.07910.00180.02010.12040.07350.06170.12200.01920.03720.07320.14190.10340.10340.03310.05400.0058-0.00850.35100.13540.06390.1556-0.02430.02750.02720.05330.1121 | 0.05750.08910.06260.07900.10070.08200.05780.13390.11990.06440.06370.10760.43190.12500.00840.32270.02230.04430.04820.04540.00790.04750.01230.03970.04610.02260.01480.17110.08980.18480.1746-0.0213-0.01490.01070.02160.09890.01340.0200-0.0350-0.03940.05910.04720.03080.0141-0.0636-0.0325-0.01880.23830.01730.07490.07060.0751-0.0382-0.0819-0.10750.0468 | 0.89481.38021.02150.84420.85651.53741.69290.83011.18572.68162.27151.17740.93781.095717.37440.42051.09493.07892.8821-0.58393.98643.08734.19612.21250.44944.19735.05890.00850.67730.08350.4533-0.0825-1.345411.29193.39830.62419.09810.9562-1.0608-1.85892.39982.18803.35792.3512-0.8481-0.17830.45131.47277.82650.85322.2048-0.3240-0.7203-0.3326-0.49612.3954 |
110111112113114115116117118119120121122123124125126127128 | Hs.79353Hs.379018Hs.408312Hs.406693N/AN/AN/AN/AHs.544577Hs.534255Hs.509736Hs.509736Hs.520640Hs.520640N/AN/A | NM_007111NM_006286NM_000546NM_003334L08752N/AN/AN/ANM_002046NM_004048NM_007355NM_007355NM_001101NM_001101N/AN/A | TFDP1TFDP2TP53UBE1BlankPUC18BlankBlankAS1R2AS1R1AS1GAPDB2MHSPCBHSPCBACTBACTBBAS2CBAS2C | 0.06450.13820.30840.02570.04280.1037-0.0228-0.02000.03190.30810.88200.85490.22890.71790.79751.66841.76162.10832.0903 | -0.00690.05040.18530.12610.01500.0852-0.04490.02990.03950.17750.70961.35060.14851.05870.90871.46581.32681.45891.4185 | -9.30602.73911.66450.20372.84971.21710.5077-0.66920.80821.73561.24280.63301.54130.67810.87761.13821.32771.44511.4736 |
方案 Pao Pereira DNA损伤 100μg/ml Pao,24hr,LNCaP
目录# Oligo GEAarray人DNA损伤信号途径微点阵
密度 平均
Clover Clover关
阵列总数 2
总组数 2
背景 空白点:位置117,116
标准化 选择基因:位置1,121,123,124,125,126
点阵名称 Pao Rx DNA damage scan dark.GIF
分配组 组1 组2
*作为默认,组1被用作对照组。
位置 | UniGene | RefSeq# | 符号 | 组2 | 组1 | 组2/组1 |
1234567891011121314151617181920212223242526272829303132333435363738394041424344454647484950515253 | Hs.546292Hs.431048Hs.518804Hs.73722Hs.154149Hs.435561Hs.271791Hs.533526Hs.194143Hs.34012Hs.519162Hs.146607Hs.184298Hs.24529Hs.291363Hs.135471Hs.249129Hs.448590Hs.435237Hs.151573Hs.532491Hs.290758Hs.446564Hs.505777Hs.339396Hs.435981Hs.487294Hs.469872Hs.460019Hs.258429Hs.498248Hs.434873Hs.409065Hs.292493Hs.80409Hs.9701Hs.86161Hs.523510Hs.191356Hs.355348Hs.386189Hs.152983Hs.503048Hs.17253Hs.523875Hs.61188Hs.1770Hs.100299Hs.166091Hs.463978Hs.432642Hs.35947Hs.195364 | NM_002954NM_005157NM_198889NM_080649NM_014481NM_000051NM_001184NM_000489NM_007294NM_000059NM_006763NM_001239NM_001799NM_001274NM_007194NM_006384NM_001279NM_014430NM_000082NM_004075NM_021117NM_001923NM_000107NM_004083NM_007068NM_001983NM_000400NM_000122NM_005236NM_000123NM_130398NM_004629NM_004111NM_001469NM_001924NM_006705NM_002066NM_005316NM_001515NM_001516NM_016426NM_004507NM_002180NM_054111NM_001567NM_033276NM_000234NM_002311NM_002312NM_002758NM_002969NM_003925NM_000249 | RPS27AABL1ANKRD17APEX1APEX2ATMATRATRXBRCA1BRCA2BTG2CCNHCDK7CHEK1CHEK2CIB1CIDEACIDEBERCC8CRY1CRY2DDB1DDB2DDIT3DMC1ERCC1ERCC2ERCC3ERCC4ERCC5EXO1FANCGFEN1G22P1GADD45AGADD45GGMLGTF2H1GTF2H2GTF2H3GTSE1HUS1IGHMBP2IHPK3INPPL1KUB3LIG1LIG3LIG4MAP2K6MAPK12MBD4MLH1 | 0.776-0.0000.0040.009-0.0440.335-0.0150.0241.4800.0200.0880.0650.019-0.002-0.0050.317-0.014-0.0060.0650.0610.030-0.005-0.0220.876-0.0470.0440.0550.1610.028-0.069-0.066-0.0440.0831.0670.3790.1930.0680.0240.107-0.1080.0440.0990.1050.0190.007-0.0330.028-0.0390.0520.0460.1260.0360.090 | 0.8980.0570.0100.113-0.0170.181-0.0310.0090.0300.034-0.0290.093-0.025-0.034-0.0540.8260.0330.054-0.010-0.025-0.084-0.063-0.0720.0350.0410.132-0.036-0.024-0.075-0.050-0.098-0.0820.0740.9740.047-0.030-0.059-0.0160.161-0.011-0.004-0.003-0.024-0.065-0.067-0.030-0.033-0.0310.0060.111-0.026-0.0530.030 | 0.864-0.0060.4670.0802.6151.8570.5012.75249.3940.600-3.0600.695-0.7750.0470.1000.384-0.426-0.112-6.217-2.399-0.3570.0760.30924.790-1.1390.333-1.514-6.716-0.3681.3780.6750.5281.1131.0958.015-6.488-1.138-1.5190.6619.991-10.361-36.939-4.407-0.295-0.1111.104-0.8511.2638.8080.413-4.904-0.6942.994 |
54555657585960616263646566676869707172737475767778798081828384858687888990919293949596979899100101102103104105106107 | Hs.279843Hs.509523Hs.459596Hs.20555Hs.156519Hs.280987Hs.216639Hs.371225Hs.445052Hs.271353Hs.396494Hs.492208Hs.66196Hs.534331Hs.380271Hs.20930Hs.147433Hs.424932Hs.111749Hs.487470Hs.278468Hs.278467Hs.78016Hs.76556Hs.491682Hs.531879Hs.16184Hs.375684Hs.81848Hs.440960Hs.521640Hs.242635Hs.446554Hs.412587Hs.172587Hs.125244Hs.552577Hs.523220Hs.240457Hs.546282Hs.443077Hs.461925Hs.487540Hs.408846Hs.59554Hs.211602Hs.81424Hs.408312Hs.192132Hs.344812Hs.170835Hs.191334Hs.3041Hs.288867 | NM_014381NM_002431NM_002434NM_005590NM_000251NM_002439NM_002440NM_002441NM_000179NM_012222NM_018177NM_002485NM_002528NM_002452NM_002542NM_020418NM_182649NM_004208NM_000534NM_000535D38500NM_005395NM_007254NM_014330NM_006904NM_002853NM_002873NM_020165NM_006265NM_005053NM_002874NM_005732NM_002875NM_058216NM_133509NM_002878NM_002879NM_003579NM_004584NM_002894NM_016316NM_002945NM_002947NM_022367NM_014454NM_006306NM_003352NM_000546NM_005427NM_016381NM_007205NM_003362NM_021147NM_000380 | MLH3MNAT1MPGMRE11AMSH2MSH3MSH4MSH5MSH6MUTYHN4BP2NBS1NTHL1NUDT1OGG1PCBP4PCNAPDCD8PMS1PMS2PMS2L4PMS2L9PNKPPPP1R15APRKDCRAD1RAD17RAD18RAD21RAD23ARAD23BRAD50RAD51RAD51CRAD51L1RAD51L3RAD52RAD54LRAD9ARBBP8REV1LRPA1RPA3SEMA4ASESN1SMC1L1SUMO1TP53TP73TREX1TREX2UNGUNG2XPA | -0.175-0.044-0.1970.1250.1260.1240.1140.3150.0820.042-0.0320.0700.0980.1730.1120.1240.2530.1250.0990.0840.1100.0890.0560.0250.0340.057-0.0380.1550.0940.0950.206-0.0240.0280.063-0.1460.0690.0640.0040.088-0.0310.0850.044-0.1200.030-0.002-0.0470.1380.182-0.025-0.012-0.089-0.049-0.027-0.003 | -0.0340.0080.1540.0170.0720.011-0.0500.1670.0410.0350.0470.0080.0830.039-0.003-0.0540.1540.0200.057-0.0060.033-0.001-0.035-0.0510.001-0.0260.027-0.0450.0230.0010.048-0.110-0.037-0.0040.018-0.039-0.025-0.001-0.050-0.061-0.0540.041-0.012-0.019-0.028-0.0250.0150.288-0.100-0.004-0.026-0.057-0.031-0.043 | 5.158-5.234-1.2787.2811.75710.811-2.2721.8881.9971.181-0.6758.9191.1814.398-41.960-2.3151.6466.3831.733-13.3013.311-147.706-1.608-0.48644.059-2.234-1.397-3.4694.143157.7654.3070.219-0.776-14.315-8.225-1.759-2.530-5.353-1.7540.511-15721.08110.294-1.6030.0561.9118.9230.6310.2463.1893.4460.8660.8660.059 |
108109110111112113114115116117118119120121122123124125126127128 | Hs.475538Hs.98493Hs.129727Hs.549075Hs.171190Hs.388739Hs.444451N/AN/AN/AN/AHs.544577Hs.534255Hs.509736Hs.509736Hs.520640Hs.520640N/AN/A | NM_004628NM_006297NM_005431NM_005432NM_003401NM_021141NM_016653L08752N/AN/AN/ANM_002046NM_004048NM_007355NM_007355NM_001101NM_001101N/AN/A | XPCXRCC1XRCC2XRCC3XRCC4XRCC5ZAKPUC18BlankBlankAS1R2AS1R1AS1GAPDB2MHSPCBHSPCBACTBACTBBAS2CBAS2C | 0.0690.0630.020-0.0590.0080.0860.062-0.0100.030-0.0300.0240.0340.3720.8300.2200.8730.8561.4001.2652.0822.005 | -0.037-0.034-0.051-0.0600.0820.131-0.0560.002-0.0190.019-0.0310.0740.2490.9490.0340.8461.0721.1141.1201.1101.061 | -1.883-1.839-0.3990.9790.0980.659-1.124-6.046-1.565-1.565-0.7720.4611.4950.8746.4131.0310.7991.2571.1291.8751.889 |
方案 Rauwolfia DNA损伤 500μg/ml Pao 24hr LNCaP
目录# Oligo GEAarray人DNA损伤信号途径微点阵
密度 平均
Clover Clover关
阵列总数 2
总组数 2
背景 空白点:位置117,116
标准化 选择基因:位置1,121,123,124,125,126
点阵名称 Rauw Rx DNA damage scans.GIF1
分配组 组1 组2
*作为默认,组1被用作对照组。
位置 | UniGene | RefSeq# | 符号 | 组2 | 组1 | 组2/组1 |
1234567891011121314151617181920212223242526272829303132333435363738394041424344454647484950515253 | Hs.546292Hs.431048Hs.518804Hs.73722Hs.154149Hs.435561Hs.271791Hs.533526Hs.194143Hs.34012Hs.519162Hs.146607Hs.184298Hs.24529Hs.291363Hs.135471Hs.249129Hs.448590Hs.435237Hs.151573Hs.532491Hs.290758Hs.446564Hs.505777Hs.339396Hs.435981Hs.487294Hs.469872Hs.460019Hs.258429Hs.498248Hs.434873Hs.409065Hs.292493Hs.80409Hs.9701Hs.86161Hs.523510Hs.191356Hs.355348Hs.386189Hs.152983Hs.503048Hs.17253Hs.523875Hs.61188Hs.1770Hs.100299Hs.166091Hs.463978Hs.432642Hs.35947Hs.195364 | NM_002954NM_005157NM_198889NM_080649NM_014481NM_000051NM_001184NM_000489NM_007294NM_000059NM_006763NM_001239NM_001799NM_001274NM_007194NM_006384NM_001279NM_014430NM_000082NM_004075NM_021117NM_001923NM_000107NM_004083NM_007068NM_001983NM_000400NM_000122NM_005236NM_000123NM_130398NM_004629NM_004111NM_001469NM_001924NM_006705NM_002066NM_005316NM_001515NM_001516NM_016426NM_004507NM_002180NM_054111NM_001567NM_033276NM_000234NM_002311NM_002312NM_002758NM_002969NM_003925NM_000249 | RPS27AABL1ANKRD17APEX1APEX2ATMATRATRXBRCA1BRCA2BTG2CCNHCDK7CHEK1CHEK2CIB1CIDEACIDEBERCC8CRY1CRY2DDB1DDB2DDIT3DMC1ERCC1ERCC2ERCC3ERCC4ERCC5EXO1FANCGFEN1G22P1GADD45AGADD45GGMLGTF2H1GTF2H2GTF2H3GTSE1HUS1IGHMBP2IHPK3INPPL1KUB3LIG1LIG3LIG4MAP2K6MAPK12MBD4MLH1 | 0.6354-0.0417-0.0848-0.0515-0.06920.0617-0.05960.12840.1155-0.0404-0.0746-0.0194-0.0500-0.0584-0.03610.67820.0004-0.0294-0.0554-0.0779-0.02690.0006-0.00080.98450.03360.0759-0.01310.0027-0.03130.03610.03830.19940.03250.99260.04170.0694-0.01170.02960.07900.20030.04110.06710.00850.02270.04060.06790.03610.29260.09960.0142-0.01770.02400.0377 | 0.93380.0205-0.00550.16620.00760.1933-0.0426-0.02990.16890.0103-0.00840.1838-0.0158-0.0986-0.06240.89830.0297-0.02420.0219-0.0613-0.0423-0.0534-0.06070.0360-0.06830.0155-0.0434-0.0257-0.0660-0.0205-0.0444-0.02450.17310.98590.05450.0820-0.0211-0.01500.1478-0.04520.1202-0.0718-0.0340-0.0366-0.0286-0.0760-0.0508-0.0583-0.0568-0.0573-0.0729-0.03650.0497 | 0.6805-2.034015.4607-0.3097-9.12340.31911.3992-4.30050.6834-3.91508.8919-0.10553.16300.59190.57740.75490.01401.2141-2.52611.27120.6359-0.01170.013727.3602-0.49164.89720.3025-0.10560.4737-1.7594-0.8642-8.13170.18781.00680.76420.84660.5521-1.97210.5344-4.43280.3415-0.9346-0.2510-0.6202-1.4229-0.8939-0.7093-5.0231-1.7539-0.24740.2429-0.65720.7590 |
54555657585960616263646566676869707172737475767778798081828384858687888990919293949596979899100101102103104105106107108 | Hs.279843Hs.509523Hs.459596Hs.20555Hs.156519Hs.280987Hs.216639Hs.371225Hs.445052Hs.271353Hs.396494Hs.492208Hs.66196Hs.534331Hs.380271Hs.20930Hs.147433Hs.424932Hs.111749Hs.487470Hs.278468Hs.278467Hs.78016Hs.76556Hs.491682Hs.531879Hs.16184Hs.375684Hs.81848Hs.440960Hs.521640Hs.242635Hs.446554Hs.412587Hs.172587Hs.125244Hs.552577Hs.523220Hs.240457Hs.546282Hs.443077Hs.461925Hs.487540Hs.408846Hs.59554Hs.211602Hs.81424Hs.408312Hs.192132Hs.344812Hs.170835Hs.191334Hs.3041Hs.288867Hs.475538 | NM_014381NM_002431NM_002434NM_005590NM_000251NM_002439NM_002440NM_002441NM_000179NM_012222NM_018177NM_002485NM_002528NM_002452NM_002542NM_020418NM_182649NM_004208NM_000534NM_000535D38500NM_005395NM_007254NM_014330NM_006904NM_002853NM_002873NM_020165NM_006265NM_005053NM_002874NM_005732NM_002875NM_058216NM_133509NM_002878NM_002879NM_003579NM_004584NM_002894NM_016316NM_002945NM_002947NM_022367NM_014454NM_006306NM_003352NM_000546NM_005427NM_016381NM_007205NM_003362NM_021147NM_000380NM_004628 | MLH3MNAT1MPGMRE11AMSH2MSH3MSH4MSH5MSH6MUTYHN4BP2NBS1NTHL1NUDT1OGG1PCBP4PCNAPDCD8PMS1PMS2PMS2L4PMS2L9PNKPPPP1R15APRKDCRAD1RAD17RAD18RAD21RAD23ARAD23BRAD50RAD51RAD51CRAD51L1RAD51L3RAD52RAD54LRAD9ARBBP8REV1LRPA1RPA3SEMA4ASESN1SMC1L1SUMO1TP53TP73TREX1TREX2UNGUNG2XPAXPC | 0.03380.07540.25360.12840.06520.02130.00920.14960.15360.14630.36330.06480.09150.01630.01250.06810.15170.18360.36740.11840.05360.05770.05710.06880.10770.21470.34620.08440.05540.07960.1207-0.01020.10020.31260.27340.1080-0.00460.01460.0523-0.00880.05980.30610.24090.05960.0046-0.02940.08920.16760.04900.13690.23920.0117-0.0131-0.02440.0031 | -0.0473-0.01920.0287-0.0755-0.0415-0.1175-0.07100.16090.0513-0.0058-0.0276-0.0266-0.0097-0.1196-0.0127-0.04240.1196-0.0066-0.0366-0.0239-0.0026-0.0126-0.00100.00790.08280.01260.06020.00050.03470.00400.16490.02080.02240.06160.1962-0.0608-0.0423-0.01600.04030.01580.08130.13490.0896-0.0650-0.0878-0.04520.08580.35420.00560.11050.0889-0.0269-0.08500.0261-0.0494 | -0.7141-3.92898.8305-1.7000-1.5730-0.1810-0.12920.93012.9933-25.1854-13.1648-2.4344-9.4499-0.1360-0.9809-1.60591.2689-27.7528-10.0309-4.9568-20.7457-4.5867-58.98128.69831.301617.05525.7514174.36051.597919.73500.7317-0.49064.46945.07161.3935-1.77460.1085-0.91321.2967-0.55350.73552.26952.6902-0.9166-0.05220.65041.03910.47318.67191.23882.6909-0.43310.1544-0.9328-0.0633 |
109110111112113114115116117118119120121122123124125126127128 | Hs.98493Hs.129727Hs.549075Hs.171190Hs.388739Hs.444451N/AN/AN/AN/AHs.544577Hs.534255Hs.509736Hs.509736Hs.520640Hs.520640N/AN/A | NM_006297NM_005431NM_005432NM_003401NM_021141NM_016653L08752N/AN/AN/ANM_002046NM_004048NM_007355NM_007355NM_001101NM_001101N/AN/A | XRCC1XRCC2XRCC3XRCC4XRCC5ZAKPUC18BlankBlankAS1R2AS1R1AS1GAPDB2MHSPCBHSPCBACTBACTBBAS2CBAS2C | -0.02100.03060.24050.25010.06810.0117-0.03900.0044-0.00440.09900.23450.38990.33740.09770.95890.99471.52661.54701.53661.5714 | -0.03130.01270.01180.06940.0699-0.00350.02030.0082-0.00820.01570.05360.19440.95670.06871.01381.02531.03381.03661.02000.9833 | 0.67242.403320.41733.60440.9754-3.2876-1.91680.53180.53186.32464.37652.00540.35271.42190.94580.97021.47661.49241.50651.5980 |
Claims (28)
1.一种用于治疗前列腺癌或延缓其发作的方法,其包括给怀疑易感或患有癌症前期或前列腺癌的受试者施用有效量的黄佩瑞任和鸡骨常山碱混合物。
2.权利要求1的方法,其中所述黄佩瑞任和鸡骨常山碱分别包含在天然提取物中。
3.权利要求2的方法,其中所述天然提取物分别衍生于Pao Pereira和Rauwolfia Vomitora。
4.权利要求3的方法,其中所述Pao Pereira的提取物含有黄佩瑞任,和Rauwolfia Vomitora提取物含有鸡骨常山碱。
5.权利要求4的方法,其以X∶Y的比例组合。
6.权利要求1的方法,其中所述黄佩瑞任和鸡骨常山碱是合成的。
7.权利要求1的方法,其中所述黄佩瑞任和鸡骨常山碱是以纯化的形式。
8.权利要求1的方法,其中所述混合物由将黄佩瑞任和鸡骨常山碱分别施用给受试者而形成。
9.权利要求1的方法,其中所述受试者是处于高危组中。
10.权利要求9的方法,其中所述高危组包括具有高PSA计数、BPH(良性前列腺增生)症状或前列腺上皮内瘤形成(PIN)症状的受试者。
11.权利要求1的方法,其中所述受试者已被诊断患有前列腺癌,但是具有如更低的Gleason得分所证明的非侵入性的肿瘤。
12.权利要求1的方法,其中所述受试者正经受癌症治疗,包括外科手术、化学治疗、冷冻治疗或放射性治疗。
13.权利要求1的方法,其中所述用量足以减轻BPH(良性前列腺增生)的症状或降低升高的PSA水平。
14.权利要求1的方法,其中所述施用是口服施用。
15.权利要求14的方法,其中所述口服施用是通过片剂或胶囊。
16.权利要求1的方法,其中所述有效量足以在癌细胞中诱导细胞程序性死亡。
17.一种用于治疗前列腺癌的组合物,其包括有效量的黄佩瑞任和鸡骨常山碱的混合物。
18.权利要求17的组合物,其中所述黄佩瑞任和鸡骨常山碱分开包含在天然提取物中。
19.权利要求17的组合物,其中所述有效量足以减轻BPH(良性前列腺增生)的症状或降低升高的PSA水平。
20.权利要求17的组合物,其是以适于口服施用的形式。
21.权利要求20的组合物,其中所述形式是片剂或胶囊。
22.权利要求13的组合物,其中所述天然提取物分别衍生于Pao Pereira和Rauwolfia Vomitora。
23.权利要求18的组合物,其中所述Pao Pereira的提取物含有黄佩瑞任,和Rauwolfia Vomitora的提取物含有鸡骨常山碱。
24.权利要求23的组合物,其中所述提取物是以X∶Y的比例组合。
25.权利要求17的组合物,其中所述有效量足以在癌细胞中诱导细胞程序性死亡。
26.权利要求17的组合物,其中所述黄佩瑞任和鸡骨常山碱是合成的。
27.权利要求17的组合物,其中所述黄佩瑞任和鸡骨常山碱是以纯化的形式。
28.一种试剂盒,其包括权利要求17的组合物。
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CN112601527A (zh) * | 2018-03-31 | 2021-04-02 | 分子国际研究公司 | 用于有效预防和治疗的选择性抗癌剂 |
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EP3718405A1 (en) | 2009-05-27 | 2020-10-07 | PTC Therapeutics, Inc. | Methods for treating cancer and non-neoplastic conditions |
US8703726B2 (en) * | 2009-05-27 | 2014-04-22 | Ptc Therapeutics, Inc. | Methods for treating prostate conditions |
WO2010138652A1 (en) | 2009-05-27 | 2010-12-02 | Ptc Therapeutics, Inc. | Methods for treating kaposi sarcoma |
CN103392009B (zh) * | 2011-02-24 | 2017-09-19 | 文塔纳医疗系统公司 | 前列腺活组织检查中低级pin(lg‑pin)中erg基因重排和蛋白质过表达的存在 |
KR20200035292A (ko) | 2017-08-01 | 2020-04-02 | 피티씨 테라퓨틱스, 인크. | 혈액 암 치료에 사용하기 위한 dhodh 억제제 |
CA3201624A1 (en) | 2020-12-23 | 2022-06-30 | Regeneron Pharmaceuticals, Inc. | Treatment of liver diseases with cell death inducing dffa like effector b (cideb) inhibitors |
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FR2403557A1 (fr) | 1977-09-19 | 1979-04-13 | Beljanski Mirko | Procede et reactifs de detection des substances cancerigenes et des substances anticancereuses |
FR2450607A2 (fr) * | 1978-03-13 | 1980-10-03 | Beljanski Mirko | Composition pharmaceutique contenant comme principe actif la flavopereine |
DE3172570D1 (en) | 1981-03-11 | 1985-11-14 | Mirko Beljanski | Serpentine, alstonine and sempervirine drugs for the specific inhibition of tumurous and cancerous cells |
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FR2694693B1 (fr) * | 1992-07-28 | 1994-10-28 | Abrax Bio Labs Sa | Composition pharmaceutique à base de flavopéréirine et son utilisation dans un traitement contre le virus VIH. |
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CN112601527A (zh) * | 2018-03-31 | 2021-04-02 | 分子国际研究公司 | 用于有效预防和治疗的选择性抗癌剂 |
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US20090215853A1 (en) | 2009-08-27 |
CA2578549A1 (en) | 2005-12-01 |
HK1105288A1 (en) | 2008-02-06 |
US7341749B2 (en) | 2008-03-11 |
CN101027070B (zh) | 2012-08-08 |
WO2005112964A1 (en) | 2005-12-01 |
US20050266107A1 (en) | 2005-12-01 |
JP2007538093A (ja) | 2007-12-27 |
EP1786519A1 (en) | 2007-05-23 |
EP1786519B1 (en) | 2012-09-05 |
BRPI0510139A (pt) | 2007-10-02 |
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