单核细胞趋化蛋白-1对前列腺癌PC-3M细胞系转移作用的体外实验研究
摘要
作用的体外实验研究
前列腺癌的发病率一直在欧美国家居高不下,目前仍高居男性恶性肿瘤发病率第二位。前列腺癌的发病原因复杂,且潜伏时间较长,患者往往无明显临床症状。近些年我国前列腺癌的发病率也呈逐年上升趋势,且多以中晚期患者居多,约有三分之一的患者出现骨转移症状。
在过去的10年间,前列腺癌的治疗出现了新的思路,由以往只注重肿瘤治疗本身而改变为既治疗肿瘤同时又注重调节患者体内微环境。基于对肿瘤细胞与体内微环境间相互作用的新认识,进展性前列腺癌的治疗方法发生了改变。前列腺癌细胞和患者机体微环境内不同的细胞相互作用后,肿瘤细胞的生长得以增强,这一过程以破骨细胞的加入更为显著。这种肿瘤生长的过程是与患者自身产生的细胞因子类和炎症趋化因子类物质有关系的。越来越多的研究表明单核细胞趋化蛋白-1(MCP-1)在前列腺癌发展和转移过程中发挥重要作用。日前有国外学者指出MCP-1不但具有募集单核细胞的能力,还可以促进前列腺癌细胞增殖和转移。有学者指出MCP-1在前列腺癌转移中起到正性调节作用。单核细胞趋化蛋白-1也称趋化因子配体2(Chemokine ligand 2, CCL2)被认为是和骨转移发生有着最密切的关系。骨髓成骨细胞、内皮细胞、间质细胞以及前列腺癌细胞均可产生MCP-1,同时MCP-1与调控肿瘤相关性巨噬细胞和促进破骨细胞成熟也有密切关联。另外,MCP-1与其受体(CCR2)结合后可通过细胞的自分泌和旁分泌行为诱导前列腺癌细胞发生增殖、迁移和侵袭。MCP-1通过PI3K/AKT相关机制激活survivin基因,从而降低前列腺癌细胞的凋亡率。
双链RNA对基因表达的阻断作用被称为RNA干扰,也被称为RNAi。双链RNA经酶切后会形成很多siRNA;信使RNA,即nRNA中的同源序列可以同这些siRNA的序列发生互补结合,从而致使mRNA失去应有的功能,使nRNA不能翻译产生蛋白质,达到基因沉默的效果。RNAi的治疗前景潜力巨大。许多疾病在基因病因学已经具有理论依据,并且有些疾病已经在体外试验和体内试验的模型中通过RNAi技术行靶向治疗。RNAi作为阻断肿瘤发生有关基因的有力手段已经越来越被重视。
本研究是基于以上理论依据应用RNAi技术将MCP-1基因阻断,探索MCP-1在前列腺癌细胞生长、增殖、转移等方面的作用,并试图阐述以上机制。
目的：
本实验选用具有高度转移特性的人前列腺癌PC-3M细胞,并依托RNAi技术构建了pFIV-H1/U6-MCP-1 siRNA质粒(pFIV-si-MCP-1质粒)。探讨MCP-1在前列腺癌进展和转移过程中作用,同时应用pFIV-si-MCP-1质粒行RNAi抑制PC-3M细胞中MCP-1基因的实验,观察前列腺癌细胞的形态学变化及相关基因表达变化,以及前列腺癌细胞凋亡率变化,尝试为前列腺癌的治疗提供新线索。
方法：
设立control组,si-scramble组,MCP-1组和si-MCP-1组,si-scramble组和si-MCP-1组分别予以细胞转染pFIV-si-scramble质粒和pFIV-si-MCP-1质粒,MCP-1组给予50ng/ml的MCP-1细胞培养液。采用MTT细胞比色法观察各组肿瘤细胞的抑制率变化；应用细胞划痕实验观察肿瘤细胞迁移能力变化；应用Transwell细胞侵袭实验观察肿瘤细胞侵袭能力变化；ELISA检测肿瘤细胞内MCP-1蛋白含量变化；应用TUNEL和Annexin V-FITC流式细胞术检测细胞凋亡率变化；RT-PCR和Western blot检测VEGF.Caspase-3、MMP-9及MCP-1基因的转录与表达。
结果：
本研究结果表明,与control组和si-scramble组比较,MTT细胞比色法试验中观察到MCP-1具有肿瘤细胞增殖的作用,MCP-1组细胞增殖率可达30.44±0.12%,而pFIV-si-MCP-1质粒可明显抑制肿瘤细胞增殖,si-MCP-1组细胞抑制率为56.9±0.10%；细胞划痕实验观察到MCP-1可促进肿瘤细胞迁移,而pFIV-si-MCP-1质粒可明显抑制肿瘤细胞迁移；Transwell细胞侵袭实验观察到MCP-1可增强肿瘤细胞侵袭能力,MCP-1组穿过Matrigel胶的肿瘤细胞数量明显增多(P<0.01),而pFIV-si-MCP-1质粒可明显抑制肿瘤细胞侵袭能力,肿瘤细胞转染pFIV-si-MCP-1质粒后侵袭细胞数量显著减少(P<0.01)；应用TUNEL及Annexin V-FITC处理各组细胞后激光共聚焦显微镜下观察和流式细胞仪检测均显示MCP-1可减少肿瘤细胞凋亡,而pFIV-si-MCP-1质粒可促进肿瘤细胞凋亡,各组细胞凋亡率分别为5.4±1.12％(control组),7.0±3.24％(si-scramble组),1.0±0.59%(MCP-1组)和40.8±3.02％(si-MCP-1组)；ELISA测定各组细胞蛋白中MCP-1含量分别为,63.5±11.60 pg/μg(control组),64.9±11.07 pg/μg(si-scramble组),88.1±8.45pg/μg(MCP-1组)和44.5±11.29 pg/μg(si-MCP-1组),结果显示MCP-1具有自身促进产生作用,pFIV-si-MCP-1质粒可减少MCP-1产生；RT-PCR与Western blot结果提示MCP-1可使Caspase-3基因转录与翻译下调,同时促进MMP-9、VEGF及MCP-1本身基因转录与翻译上调,pFIV-si-MCP-1质粒则可使Caspase-3基因转录与翻译上调,同时MMP-9、VEGF及MCP-1本身基因转录与翻译下调。
结论：
1.实验证明MCP-1具有促进PC-3M细胞增殖作用和减少凋亡,并且增加PC-3M细胞侵袭能力的作用。
2.上述作用与MCP-1上调VEGF、MMP-9表达和下调Caspase-3表达有关。
3.实验证明pFIV-si-MCP-1质粒对PC-3M细胞具有降低肿瘤细胞侵袭能力和促进凋亡作用。
4.上述作用与MCP-1表达受抑制后VEGF、MMP-9表达下调和Caspase-3表达上调有关。
The incidence of prostate cancer has been high in Europe and America,it is still rankedsecond in the incidence of male cancer. The etiology of prostate cancer is complex and the latency is long, patients are often no obvious clinical symptoms. In recent years the incidence of prostate cancer is also increasing, about one-third of the patients had symptoms of bone metastases.
In the past 10 years, there is a new way in the treatment of prostate cancer. Focus only on cancer treatment in the past change to the treatment of tumors at the same time as focus on regulation in microenvironment in patients. Based on the new understanding between in vivo microenvironment of tumor cells and the interaction, the treatment of prostate cancer has changed. Recently, monocyte chemoattractant protein-1 (MCP-1) has been shown to play an important role in the progression and metastasis of prostate cancer. Foreign scholars have recently found MCP-1 not only has raised the ability of monocytes, but also promote the proliferation and metastasis of prostate cancer. Some scholars have pointed out that the MCP-1 in prostate cancer metastasis positive regulatory role played. Monocyte chemoattractant protein-1 is cons-idered to have the most closely related to the occurrence of bone metastasis. Osteoblasts,endothelial cells, stromal cells and prostate cancer cells can produce MCP-1.
MCP-1 can also regulate tumor-associatiated macrophages and promote osteoclastmaturation.In addition,MCP-1 and its receptor(CCR2) complex can induce prostate cancer cellsproliferation, migration and invasion. MCP-1 can activate the survivin gene through PI3K/AKT mechanisms to reduce prostate cancer cell apoptosis.
Double-stranded RNA blocks gene expression known as RNA interference effect,also knowm as RNAi.Double-stranded RNA will be digested to many siRNA.Messenger RNA of homologous sequence can occur with these siRNA sequences,and then the mRNA lose their funcion,so translation of mRNA can not produce proteins.RNAi as a powerful tumor blocking tool for the gene has been more and more attention. Objective:
In this experiment, a highly metastatic human prostate cancer PC-3M cells, and based on RNAi technology to build pFIV-H1/U6-MCP-1 siRNA vector (pFIV-si-MCP-1 vector). Our aim was to investigate the mechanisms underlying the functional role of MCP-1 in prostate cancer progression and metastasis., while application pFIV-si-MCP-1 vector for RNAi inhibition, attempt to provide a new treatment for prostate cancer clues. Methods:
The control groups, si-scramble group, MCP-1 group and the si-MCP-1 group give to the appropriate disposal respectively.Using MTT assay to observe the inhibitory rate of tumor cells in changes.Using scratch experiments to observed cell migration changes. Using Transwell cell invasion assay to observe tumor cell invasion changes. Using ELISA to detect tumor cells MCP-1 protein content. Using TUNEL and Annexin V-FITC flow cytometry to cell observe apoptosis rate changes. Using RT-PCR and Western blot to detect VEGF, Caspase-3, MMP-9 and MCP-1 gene transcription and expression.
Results:
With the control group and the si-scramble group, the results show that MCP-1 was observed with tumor cell proliferation in the MTT test, cell proliferation rate of MCP-1 group was 30.4±0.12%.The pFIV-si-MCP-1 vector can inhibit tumor cell proliferation, the cell inhibition rate of si-MCP-1 group was 56.9±0.10%. Observed in cell scratch experiment MCP-1 can promote tumor cell migration, and pFIV-si-MCP-1 vector could inhibit tumor cell migration. In the transwell cell invasion assay MCP-1 can enhance the invasive ability of tumor cells, MCP-1 group significantly increased the number of plastic through the Matrigel (P<0.01), while the pFIV-si-MCP-1 vector can inhibit tumor cell invasion, Tumor cells transfected pFIV-si-MCP-1 vector significantly reduced the number of invasive cells (P<0.01). In TUNEL and Annexin V-FITC test in each group were observed under confocal laser microscopy and flow cytometry have shown that MCP-1 can reduce the tumor cell apoptosis, and pFIV-si-MCP-1 can promote tumor cell to apoptosis, the apoptosis rate in each group were 5.4±1.12%(control group),7.0±3.24% (si-scramble group),1.0±0.59%(MCP-1 group) and 40.8±3.02%(si-MCP-1 group). In the ELISA assay, the concentrations of MCP-1 were,63.5±11.60 pg/μg (control group),64.9±11.07 pg/μg (si-scramble group),88.1±8.45 pg/μg (MCP-1 group) And 44.5±11.29 pg/μg (si-MCP-1 group), MCP-1 showed an effect with its own promotion, pFIV-si-MCP-1 MCP-1 vector can reduced MCP-1. RT-PCR and Western blot results suggest that MCP-1 can downregulates Caspase-3 gene transcription and translation, while promoting MMP-9, VEGF and MCP-1 gene transcription and translation, pFIV-si-MCP-1 vector can be The Caspase-3 gene transcription and translation upregulates, and downregulates MMP-9, VEGF and MCP-1 gene transcription and translation. Conclusion:
1. Experiments show that MCP-1 can promote the proliferation of PC-3M cells and reduced apoptosis, and increase the invasive ability of PC-3M cells.
2. The reason of these effects was MCP-1 increased with VEGF, MMP-9 expression and decreased the expression of Caspase-3.
3. pFIV-si-MCP-1 vector can reduce PC-3M cell invasion and promote apoptosis.
4. The reason of these effects was VEGF, MMP-9 expression decreased and the expression of Caspase-3 upregulated after MCP-1 expression was inhibited.
前列腺癌的发病率一直在欧美国家居高不下,目前仍高居男性恶性肿瘤发病率第二位。前列腺癌的发病原因复杂,且潜伏时间较长,患者往往无明显临床症状。近些年我国前列腺癌的发病率也呈逐年上升趋势,且多以中晚期患者居多,约有三分之一的患者出现骨转移症状。
在过去的10年间,前列腺癌的治疗出现了新的思路,由以往只注重肿瘤治疗本身而改变为既治疗肿瘤同时又注重调节患者体内微环境。基于对肿瘤细胞与体内微环境间相互作用的新认识,进展性前列腺癌的治疗方法发生了改变。前列腺癌细胞和患者机体微环境内不同的细胞相互作用后,肿瘤细胞的生长得以增强,这一过程以破骨细胞的加入更为显著。这种肿瘤生长的过程是与患者自身产生的细胞因子类和炎症趋化因子类物质有关系的。越来越多的研究表明单核细胞趋化蛋白-1(MCP-1)在前列腺癌发展和转移过程中发挥重要作用。日前有国外学者指出MCP-1不但具有募集单核细胞的能力,还可以促进前列腺癌细胞增殖和转移。有学者指出MCP-1在前列腺癌转移中起到正性调节作用。单核细胞趋化蛋白-1也称趋化因子配体2(Chemokine ligand 2, CCL2)被认为是和骨转移发生有着最密切的关系。骨髓成骨细胞、内皮细胞、间质细胞以及前列腺癌细胞均可产生MCP-1,同时MCP-1与调控肿瘤相关性巨噬细胞和促进破骨细胞成熟也有密切关联。另外,MCP-1与其受体(CCR2)结合后可通过细胞的自分泌和旁分泌行为诱导前列腺癌细胞发生增殖、迁移和侵袭。MCP-1通过PI3K/AKT相关机制激活survivin基因,从而降低前列腺癌细胞的凋亡率。
双链RNA对基因表达的阻断作用被称为RNA干扰,也被称为RNAi。双链RNA经酶切后会形成很多siRNA;信使RNA,即nRNA中的同源序列可以同这些siRNA的序列发生互补结合,从而致使mRNA失去应有的功能,使nRNA不能翻译产生蛋白质,达到基因沉默的效果。RNAi的治疗前景潜力巨大。许多疾病在基因病因学已经具有理论依据,并且有些疾病已经在体外试验和体内试验的模型中通过RNAi技术行靶向治疗。RNAi作为阻断肿瘤发生有关基因的有力手段已经越来越被重视。
本研究是基于以上理论依据应用RNAi技术将MCP-1基因阻断,探索MCP-1在前列腺癌细胞生长、增殖、转移等方面的作用,并试图阐述以上机制。
目的：
本实验选用具有高度转移特性的人前列腺癌PC-3M细胞,并依托RNAi技术构建了pFIV-H1/U6-MCP-1 siRNA质粒(pFIV-si-MCP-1质粒)。探讨MCP-1在前列腺癌进展和转移过程中作用,同时应用pFIV-si-MCP-1质粒行RNAi抑制PC-3M细胞中MCP-1基因的实验,观察前列腺癌细胞的形态学变化及相关基因表达变化,以及前列腺癌细胞凋亡率变化,尝试为前列腺癌的治疗提供新线索。
方法：
设立control组,si-scramble组,MCP-1组和si-MCP-1组,si-scramble组和si-MCP-1组分别予以细胞转染pFIV-si-scramble质粒和pFIV-si-MCP-1质粒,MCP-1组给予50ng/ml的MCP-1细胞培养液。采用MTT细胞比色法观察各组肿瘤细胞的抑制率变化；应用细胞划痕实验观察肿瘤细胞迁移能力变化；应用Transwell细胞侵袭实验观察肿瘤细胞侵袭能力变化；ELISA检测肿瘤细胞内MCP-1蛋白含量变化；应用TUNEL和Annexin V-FITC流式细胞术检测细胞凋亡率变化；RT-PCR和Western blot检测VEGF.Caspase-3、MMP-9及MCP-1基因的转录与表达。
结果：
本研究结果表明,与control组和si-scramble组比较,MTT细胞比色法试验中观察到MCP-1具有肿瘤细胞增殖的作用,MCP-1组细胞增殖率可达30.44±0.12%,而pFIV-si-MCP-1质粒可明显抑制肿瘤细胞增殖,si-MCP-1组细胞抑制率为56.9±0.10%；细胞划痕实验观察到MCP-1可促进肿瘤细胞迁移,而pFIV-si-MCP-1质粒可明显抑制肿瘤细胞迁移；Transwell细胞侵袭实验观察到MCP-1可增强肿瘤细胞侵袭能力,MCP-1组穿过Matrigel胶的肿瘤细胞数量明显增多(P<0.01),而pFIV-si-MCP-1质粒可明显抑制肿瘤细胞侵袭能力,肿瘤细胞转染pFIV-si-MCP-1质粒后侵袭细胞数量显著减少(P<0.01)；应用TUNEL及Annexin V-FITC处理各组细胞后激光共聚焦显微镜下观察和流式细胞仪检测均显示MCP-1可减少肿瘤细胞凋亡,而pFIV-si-MCP-1质粒可促进肿瘤细胞凋亡,各组细胞凋亡率分别为5.4±1.12％(control组),7.0±3.24％(si-scramble组),1.0±0.59%(MCP-1组)和40.8±3.02％(si-MCP-1组)；ELISA测定各组细胞蛋白中MCP-1含量分别为,63.5±11.60 pg/μg(control组),64.9±11.07 pg/μg(si-scramble组),88.1±8.45pg/μg(MCP-1组)和44.5±11.29 pg/μg(si-MCP-1组),结果显示MCP-1具有自身促进产生作用,pFIV-si-MCP-1质粒可减少MCP-1产生；RT-PCR与Western blot结果提示MCP-1可使Caspase-3基因转录与翻译下调,同时促进MMP-9、VEGF及MCP-1本身基因转录与翻译上调,pFIV-si-MCP-1质粒则可使Caspase-3基因转录与翻译上调,同时MMP-9、VEGF及MCP-1本身基因转录与翻译下调。
结论：
1.实验证明MCP-1具有促进PC-3M细胞增殖作用和减少凋亡,并且增加PC-3M细胞侵袭能力的作用。
2.上述作用与MCP-1上调VEGF、MMP-9表达和下调Caspase-3表达有关。
3.实验证明pFIV-si-MCP-1质粒对PC-3M细胞具有降低肿瘤细胞侵袭能力和促进凋亡作用。
4.上述作用与MCP-1表达受抑制后VEGF、MMP-9表达下调和Caspase-3表达上调有关。
The incidence of prostate cancer has been high in Europe and America,it is still rankedsecond in the incidence of male cancer. The etiology of prostate cancer is complex and the latency is long, patients are often no obvious clinical symptoms. In recent years the incidence of prostate cancer is also increasing, about one-third of the patients had symptoms of bone metastases.
In the past 10 years, there is a new way in the treatment of prostate cancer. Focus only on cancer treatment in the past change to the treatment of tumors at the same time as focus on regulation in microenvironment in patients. Based on the new understanding between in vivo microenvironment of tumor cells and the interaction, the treatment of prostate cancer has changed. Recently, monocyte chemoattractant protein-1 (MCP-1) has been shown to play an important role in the progression and metastasis of prostate cancer. Foreign scholars have recently found MCP-1 not only has raised the ability of monocytes, but also promote the proliferation and metastasis of prostate cancer. Some scholars have pointed out that the MCP-1 in prostate cancer metastasis positive regulatory role played. Monocyte chemoattractant protein-1 is cons-idered to have the most closely related to the occurrence of bone metastasis. Osteoblasts,endothelial cells, stromal cells and prostate cancer cells can produce MCP-1.
MCP-1 can also regulate tumor-associatiated macrophages and promote osteoclastmaturation.In addition,MCP-1 and its receptor(CCR2) complex can induce prostate cancer cellsproliferation, migration and invasion. MCP-1 can activate the survivin gene through PI3K/AKT mechanisms to reduce prostate cancer cell apoptosis.
Double-stranded RNA blocks gene expression known as RNA interference effect,also knowm as RNAi.Double-stranded RNA will be digested to many siRNA.Messenger RNA of homologous sequence can occur with these siRNA sequences,and then the mRNA lose their funcion,so translation of mRNA can not produce proteins.RNAi as a powerful tumor blocking tool for the gene has been more and more attention. Objective:
In this experiment, a highly metastatic human prostate cancer PC-3M cells, and based on RNAi technology to build pFIV-H1/U6-MCP-1 siRNA vector (pFIV-si-MCP-1 vector). Our aim was to investigate the mechanisms underlying the functional role of MCP-1 in prostate cancer progression and metastasis., while application pFIV-si-MCP-1 vector for RNAi inhibition, attempt to provide a new treatment for prostate cancer clues. Methods:
The control groups, si-scramble group, MCP-1 group and the si-MCP-1 group give to the appropriate disposal respectively.Using MTT assay to observe the inhibitory rate of tumor cells in changes.Using scratch experiments to observed cell migration changes. Using Transwell cell invasion assay to observe tumor cell invasion changes. Using ELISA to detect tumor cells MCP-1 protein content. Using TUNEL and Annexin V-FITC flow cytometry to cell observe apoptosis rate changes. Using RT-PCR and Western blot to detect VEGF, Caspase-3, MMP-9 and MCP-1 gene transcription and expression.
Results:
With the control group and the si-scramble group, the results show that MCP-1 was observed with tumor cell proliferation in the MTT test, cell proliferation rate of MCP-1 group was 30.4±0.12%.The pFIV-si-MCP-1 vector can inhibit tumor cell proliferation, the cell inhibition rate of si-MCP-1 group was 56.9±0.10%. Observed in cell scratch experiment MCP-1 can promote tumor cell migration, and pFIV-si-MCP-1 vector could inhibit tumor cell migration. In the transwell cell invasion assay MCP-1 can enhance the invasive ability of tumor cells, MCP-1 group significantly increased the number of plastic through the Matrigel (P<0.01), while the pFIV-si-MCP-1 vector can inhibit tumor cell invasion, Tumor cells transfected pFIV-si-MCP-1 vector significantly reduced the number of invasive cells (P<0.01). In TUNEL and Annexin V-FITC test in each group were observed under confocal laser microscopy and flow cytometry have shown that MCP-1 can reduce the tumor cell apoptosis, and pFIV-si-MCP-1 can promote tumor cell to apoptosis, the apoptosis rate in each group were 5.4±1.12%(control group),7.0±3.24% (si-scramble group),1.0±0.59%(MCP-1 group) and 40.8±3.02%(si-MCP-1 group). In the ELISA assay, the concentrations of MCP-1 were,63.5±11.60 pg/μg (control group),64.9±11.07 pg/μg (si-scramble group),88.1±8.45 pg/μg (MCP-1 group) And 44.5±11.29 pg/μg (si-MCP-1 group), MCP-1 showed an effect with its own promotion, pFIV-si-MCP-1 MCP-1 vector can reduced MCP-1. RT-PCR and Western blot results suggest that MCP-1 can downregulates Caspase-3 gene transcription and translation, while promoting MMP-9, VEGF and MCP-1 gene transcription and translation, pFIV-si-MCP-1 vector can be The Caspase-3 gene transcription and translation upregulates, and downregulates MMP-9, VEGF and MCP-1 gene transcription and translation. Conclusion:
1. Experiments show that MCP-1 can promote the proliferation of PC-3M cells and reduced apoptosis, and increase the invasive ability of PC-3M cells.
2. The reason of these effects was MCP-1 increased with VEGF, MMP-9 expression and decreased the expression of Caspase-3.
3. pFIV-si-MCP-1 vector can reduce PC-3M cell invasion and promote apoptosis.
4. The reason of these effects was VEGF, MMP-9 expression decreased and the expression of Caspase-3 upregulated after MCP-1 expression was inhibited.
引文
[1]Ringpis GE, Lathrop RH, Aphasizhev R. iCODA:RNAi-Based Indu cible Knock-In System in Trypanosoma brucei[J]. Methods Mol Biol,2011,7 18:23-37.
[2]Yin G, Sun Z, Liu N,et al. Production of double-stranded RNA for interference with TMV infection utilizing a bacterial prokaryotic expression system[J]. Appl Microbiol Biotechnol,2009,84(2):323-333.
[3]Craig P, Hunter. Shrinking the black box of RNAi[J]. Current Biology, 2000,10(4):R137-140.
[4]Travis B J. For geneticists, interference becomes an asset[J]. Science News,2000,157(3):36.
[5]Higuchi Y, Kawakami S, Hashida M. Strategies for in vivo delivery of siRNAs:recent progress [J]. BioDrugs,2010,24(3):195-205.
[6]Ketting RF, Haverkamp TH, van Luenen HG, et al. Mut-7 of C. elegans, required for transposon silencing and RNA interference, is a homolog of Werner syndrome helicase and RnaseD[J]. Cell.1999,99(2):133-41.
[7]Dzitoyeva S, Dimitrijevic N, Manev H. Gamma-aminobutyric acid B receptor 1 mediates behavior-impairing actions of alcohol in Drosophila:adult RNA interference and pharmacological evidence[J]. Proc Natl Acad Sci U S A, 2003,100(9):5485-5490.
[8]Gautier EL, Jakubzick C, Randolph GJ. Regulation of the migration and survival of monocyte subsets by chemokine receptors and its relevance to atherosclerosis[J]. Arterioscler Thromb Vasc Biol,2009,29(10):1412-1418.
[9]Lackner P, Kuenz B, Reindl M,et al. Antibodies to myelin oligode ndrocyte glycoprotein in HIV-1 associated neurocognitive disorder:a cross-sectional cohort study[J]. J Neuroinflammation,2010,7:79.
[10]Miyazaki K, Yamasaki N, Oda H,et al. Enhanced expression of p210BCR/ABL and aberrant expression of Zfp423/ZNF423 induce blast crisis of chronic myelogenous leukemia[J]. Blood,2009,113(19):4702-4710.
[11]Rahmani M, Nguyen TK, Dent P,et al. The multikinase inhibitor sorafenib induces apoptosis in highly imatinib mesylate-resistant bcr/abl+ human leukemia cells in association with signal transducer and activator of transcription 5 inhibition and myeloid cell leukemia-1 down-regulation[J]. Mol Pharmacol,2007,72(3):788-795.
[12]Buchert M, Papin M, Bonnans C,et al. Symplekin promotes tumorige nicity by up-regulating claudin-2 expression[J]. Proc Natl Acad Sci U S A,2010,107(6):2628-2633.
[13]Futami M, Hatano T, Soda Y, et al. RNAi-mediated silencing of p190Bcr-Abl inactivates Stat5 and cooperates with imatinib mesylate and 17-allylamino-17-demetoxygeldanamycin in selective killing of p190 Bcr-A bl-expressing leukemia cells[J]. Leukemia,2008,22(6):1131-1138.
[14]Zhang X, Li J, Qiu Z, et al. Co-suppression of MDR1 (multidrug resistance 1) and GCS (glucosylceramide synthase) restores sensitivity to multidrug resistance breast cancer cells by RNA interference (RNAi)[J]. Cancer Biol Ther,2009,8(12):1117-1121.
[15]Song E, Lee SK, Wang J, et al. RNA interference targeting Fas protects mice from fulminant hepatitis[J]. Nat Med,2003,9(3):347-351.
[16]Zender L, Hutker S, Liedtke C, et al.Caspase 8 small interfering RNA prevents acute liver failure in mice[J]. Proc Natl Acad Sci USA, 2003,100(13):7797-7802.
[17]Ullu E, Tschudi C, Chakraborty T. RNA interference in protozoan parasites[J]. Cell Microbiol,2004,6(6):509-519.
[18]Jolly C, Booth NJ, Neil SJ. Cell-cell spread of human immunodeficiency virus type 1 overcomes tetherin/BST-2-mediated restriction in T cells[J].J Virol,2010,84(23):12185-12199.
[19]von Eije KJ, ter Brake O, Berkhout B. Human immunodeficiency virus type 1 escape is restricted when conserved genome sequences are targeted by RNA interference[J]. J Virol,2008,82(6):2895-2903.
[20]Wang FX, Huang J, Zhang H,et al. APOBEC3G upregulation by alpha interferon restricts human immunodeficiency virus type 1 infection in human peripheral plasmacytoid dendritic cells[J]. J Gen Virol,2008,89(Pt 3):722-730.
[21]Turner AM, De La Cruz J, Morris KV. Mobilization-competent Lentiviral Vector-mediated Sustained Transcriptional Modulation of HIV-1 Expression[J]. Mol Ther,2009,17(2):360-368.
[22]von Eije KJ, ter Brake O, Berkhout B. Stringent testing identifies highly potent and escape-proof anti-HIV short hairpin RNAs[J]. J Gene Med, 2009,11(6):459-467.
[23]Nishi J, Minamino T, Miyauchi H,et al. Vascular endothelial growth factor receptor-1 regulates postnatal angiogenesis through inhibition of the excessive activation of Akt[J]. Circ Res,2008,103(3):261-268.
[24]Takeda A, Tsukuda M, Mizumoto H,et al. A plant RNA virus suppresses RNA silencing through viral RNA replication[J]. EMBO J,2005,2 4(17):3147-3157.
[25]Agrawal L, Maxwell CR, Peters PJ,et al. Complexity in human immunodeficiency virus type 1 (HIV-1) co-receptor usage:roles of CCR3 and CCR5 in HIV-1 infection of monocyte-derived macrophages and brain mic rog lia[J]. J Gen Virol,2009,90(Pt 3):710-722.
[26]Zamore PD. Plant RNAi:how a viral silencing suppressor inactivates siRNA[J]. Curr Biol,2004,14(5):198-200.
[27]Rakhshandehroo F, Takeshita M, Squires J,et al. The influence of RNA-dependent RNA polymerase 1 on potato virus Y infection and on other antiviral response genes[J]. Mol Plant Microbe Interact,2009,22(10):1312-1318.
[28]Delgadillo MO, Saenz P, Salvador B,et al. Human influenza virus NS1 protein enhances viral pathogenicity and acts as an RNA silencing suppr essor in plants[J]. J Gen Virol,2004,85(4):993-999.
[29]Bucher E, Hemmes H, de Haan P,et al. The influenza A virus NS1 pro tein binds small interfering RNAs and suppresses RNA silencing in pla nts[J]. J Gen Virol,2004,85(4):983-991.
[30]Li WX, Li H, Lu R, et al. Interferon antagonist proteins of influenza and vaccinia viruses are suppressors of RNA silencing[J].Proc Natl Acad Sci U SA,2004,101(5):1350-1355.
[31]Dickson ME, Tian X, Liu X, et al. Synthetic microRNA designed to target glioma-associated antigen 1 transcription factor inhibits division and induces late apoptosis in pancreatic tumor cells[J]. Clin Cancer Res, 2006,12(21):6557-6564.
[32]Klunker S, Chong MM, Mantel PY, et al. Transcription factors RUNX1 and RUNX3 in the induction and suppressive function of Foxp3+ inducible regulatory T cells[J]. J Exp Med,2009,206(12):2701-2715.
[33]Li Y, Zhao M, Yin H, et al. Overexpression of the growth arrest and DNA damage-induced 45alpha gene contributes to autoimmunity by promoting DNA demethylation in lupus T cells[J]. Arthritis Rheum,2010,62(5):1438-1447.
[34]Farina F, Alberti A, Breuil N, et al. Differential expression pattern of the four mitochondrial adenine nucleotide transporter ant genes and their roles during the development of Caenorhabditis elegans[J]. Dev Dyn,2008,23 7(6):1668-1681.
[35]McAllister CS, Samuel CE. The RNA-activated protein kinase enhances the induction of interferon-beta and apoptosis mediated by cytop las mic RNA sensors[J]. J Biol Chem,2009,284(3):1644-1651.
[36]Ely A, Naidoo T, Arbuthnot P. Efficient silencing of gene expression with modular trimeric Pol Ⅱ expression cassettes comprising microRNA shutt les[J]. Nucleic Acids Res,2009,37(13):e91.
[37]Lee SK, Li W, Ryu SE,et al. Vacuolar (H+)-ATPases in Caenorh abditis elegans:what can we learn about giant H+pumps from tiny worms[J]? Biochim Biophys Acta,2010,1797(10):1687-1695.
[38]Wang G, Reinke V. A C. elegans Piwi, PRG-1, regulates 21U-RNAs during spermatogenesis[J]. Curr Biol,2008,18(12):861-867.
[39]Marchais A, Bohn C, Bouloc P, et al. RsaOG, a new staphylococcal family of highly transcribed non-coding RNA[J]. RNA Biol, 2010,7(2):116-119.
[40]Alcazar RM, Lin R, Fire AZ. Transmission dynamics of heritable silencing induced by double-stranded RNA in Caenorhabditis elegans[J]. Genetics,2008,180(3):1275-1288.
[41]Kennerdell JR, Carthew RW.Use of dsRNA-mediated genetic interference to demonstrate that frizzled and frizzled 2 act in the wingless pathway[J]. Cell,1998,95(7):1017-1026.
[42]von Eije KJ, ter Brake O, Berkhout B. Stringent testing identifies highly potent and escape-proof anti-HIV short hairpin RNAs[J]. J Gene Med, 2009,11(6):459-467.
[43]de Fougerolles A, Vornlocher HP, Maraganore J, et al. Interfering with disease:a progress report on siRNA-based therapeutics[J]. Nat Rev Drug Discov,2007,6(6):443-453.
[44]Swayze EE, Bhat B. Antisense Drug Technologies, Principles, Strategies and Applications[M].2nd ed. New York:Taylor and Francis Group,2008.
[45]Haussecker D. The business of RNAi therapeutics [J]. Hum Gene Ther, 2008,19(5):451-462.
[46]Novobrantseva TI, Akinc A, Borodovsky A, et al. Delivering silence: advancements in developing siRNA therapeutics[J]. Curr Opin Drug Discov Devel,2008, 11(2):217-224.
[47]Whitehead KA, Langer R, Anderson DG. Knocking down barriers:advances in siRNA delivery[J]. Nat Rev Drug Discov,2009, 8(2):129-138.
[48]Bitko V, Musiyenko A, Shulyayeva O, et al. Inhibition of respiratory viruses by nasally administered siRNA[J]. Nat Med,2005,11(1):50-55.
[49]Alvarez R, Elbashir S, Borland T, et al.RNA interference-mediated silencing of the respiratory syncytial virus nucleocapsid defines a potent anti viral strategy[J]. Antimicrob Agents Chemother,2009,53(9):3952-3962.
[50]Palliser D, Chowdhury D, Wang QY, et al. An siRNA-based microbicide protects mice from lethal herpes simplex virus 2 infection[J]. Nat u re,2006,439(7072):89-94.
[51]Querbes W, Ge P, Zhang W, et al. Direct CNS delivery of siRNA mediates robust silencing in oligodendrocytes[J]. Oligonucleotides,2009,1 9(1):23-30.
[52]Kleinman ME, Yamada K, Takeda A, et al. Sequence-and target-independent angiogenesis suppression by siRNA via TLR3[J]. Nature, 2008,452(7187):591-597.
[53]Shen J, Samul R, Silva RL, et al. Suppression of ocular neovascularization with siRNA targeting VEGF receptor 1 [J]. Gene Ther,2006, 13(3):225-234.
[54]Soutschek J, Akinc A, Bramlage B, et al.Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs[J]. Nature, 2004,432(7014):173-178.
[55]Wolfrum C, Shi S, Jayaprakash KN, et al. Mechanisms and optimiz ation of in vivo delivery of lipophilic siRNAs[J]. Nat Biotechnol,2007, 25(10):1149-1157.
[56]Morrissey DV, Lockridge JA, Shaw L, et al.Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs[J]. Nat Biotechnol,20 05,23(8):1002-1007.
[57]Zimmermann TS, Lee AC, Akinc A,et al.RNAi-mediated gene silencing in non-human primates[J]. Nature,2006,441(7089):111-114.
[58]Abrams MT, Koser ML, Seitzer J, et al.Evaluation of efficacy, biodistribution, and inflammation for a potent siRNA nanoparticle:effect of dexamethasone cotreatment[J]. Mol Ther,2010,18(1):171-180.
[59]Akinc A, Querbes W, De S, et al.Targeted Delivery of RNAi Therap eutics With Endogenous and Exogenous Ligand-Based Mechanisms [J]. Mol Ther,2010,18(7):1357-1364.
[60]Rozema DB, Lewis DL, Wakefield DH, et al.Dynamic polyconjugates for targeted in vivo delivery of siRNA to hepatocytes[J]. Proc Natl Acad Sci U SA,2007,104(32):12982-12987.
[61]Bartlett DW, Su H, Hildebrandt IJ, et al. Impact of tumorspecific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging[J]. Proc Natl Acad Sci USA,2007, 104(39):15549-15554.
[62]Semple SC, Akinc A, Chen J, et al. Rational design of cationic lipids for siRNA delivery[J]. Nat Biotechnol,2010,28(2):172-176.
[63]Frank-Kamenetsky M, Grefhorst A, Anderson NN, et al. Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates[J]. Proc Natl Acad Sci USA,2008, 105(33):11915-11920.
[64]Akinc A, Goldberg M, Qin J, et al. Development of lipidoid siRNA formulations for systemic delivery to the liver[J]. Mol Ther, 2009,17(5):872-879.
[65]Love KT, Mahon KP, Levins CG, et al. Lipid-like materials for low-dose, in vivo gene silencing[J].Proc Natl Acad Sci USA,2010, 107(5):1864-1869.
[66]Judge AD, Robbins M, Tavakoli I, et al. Confirming the RNAi-mediated mechanism of action of siRNA-based cancer therapeutics in mice[J]. J Clin Invest,2009,119(3):661-673.
[67]Song E, Zhu P, Lee SK, et al.Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors[J]. Nat Biotechnol,2005, 23(6):709-717.
[68]Peer D, Zhu P, Carman CV, et al.Selective gene silencing in activated leukocytes by targeting siRNAs to the integrin lymphocyte function-associated antigen-1[J]. Proc Natl Acad Sci USA,2007,104(10):4095-4100.
[69]Peer D, Park EJ, Morishita Y, et al.Systemic leukocytedirected siRNA delivery revealing cyclin Dl as an anti-inflammatory target[J]. Science,2008, 319(5863):627-630.
[70]Aouadi M, Tesz GJ, Nicoloro SM, et al.Orally delivered siRNA targeting macrophage Map4k4 suppresses systemic inflammation[J]. Nature, 2009,458(7242):1180-1184.
[71]Jackson AL, Linsley PS. Recognizing and avoiding siRNA off-target effects for target identification and therapeutic application[J]. Nat Rev Drug Discov,2010,9(1):57-67.
[72]Jackson AL, Bartz SR, Schelter J,et al. Expression profiling reveals off-target gene regulation by RNAi[J]. Nat Biotechnol,2003,21(6):635-637.
[73]Jackson AL, Burchard J, Schelter J, et al.Widespread siRNA "off-target" transcript silencing mediated by seed region sequence complem entarity[J]. RNA,2006(7),12:1179-1187.
[74]Birmingham A, Anderson EM, Reynolds A,et al.3'UTR seed matches, but not overall identity, are associated with RNAi off-targets [J]. Nat Methods,2006,3:199-204.
[75]Grimm D, Streetz KL, Jopling CL, et al.Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways[J]. Nature, 2006,441(7092):537-541.
[76]Khan AA, Betel D, Miller ML, et al. Transfection of small RNAs globally perturbs gene regulation by endogenous microRNAs[J]. Nat Biotec hn ol,2009,27(6):549-555.
[77]Hornung V, Guenthner-Biller M, Bourquin C, et al.Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7[J]. Nat Med,2005,11(3):263-270.
[78]Judge AD, Sood V, Shaw JR, et al.Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA[J]. Nat Biotechnol, 2005,23(4):457-642.
[79]Sioud M. Induction of inflammatory cytokines and interferon responses by double-stranded and single-stranded siRNAs is sequence-depen dent and requires endosomal localization[J]. J Mol Biol,2005,348(5):1079-1090.
[80]Aleman LM, Doench J, Sharp PA. Comparison of siRNA-induced offtarget RNA and protein effects[J]. RNA,2007,13(3):385-395.
[81]Bilanges B, Stokoe D. Direct comparison of the specificity of gene silencing using antisense oligonucleotides and RNAi[J]. Biochem J,2005, 388(2):573-583.
[82]Fisher AA, Ye D, Sergueev DS, et al. Evaluating the specificity of antisense oligonucleotide conjugates. A DNA array analysis[J]. J Biol Chem, 2002,277(25):22980-22984.
[83]Irwin RD, Parker JS, Lobenhofer EK,et al. Transcriptional profiling of the left and median liver lobes of male f344/n rats following exposure to acetaminophen[J]. Toxicol Pathol,2005,33(1):111-1117.
[84]Lin Z, Crockett DK, Jenson SD,et al. Quantitative proteomic and transcriptional analysis of the response to the p38 mitogen-activated protein kinase inhibitor SB2035380 in transformed follicular lymphoma cells[J]. Mol Cell Proteomics,2004,3(8):820-833.
[85]Robbins M, Judge A, MacLachlan I. siRNA and innate immunity[J]. Oligonucleotides,2009,19(2):89-102.
[86]Yoneyama M, Kikuchi M, Natsukawa T, et al. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiv iral responses[J].Nat Immunol,2004,5(7):730-737.
[87]Korth MJ, Lyons CN, Wambach M,et al. Cloning, expression, and cellular localization of the oncogenic 58-kDa inhibitor of the RNA-activated human and mouse protein kinase[J]. Gene,1996,170(2):181-188.
[88]Robbins M, Judge A, Ambegia E, et al. Misinterpreting the therapeutic effects of small interfering RNA caused by immune stimulation[J]. Hum Gene Ther,2008,19(10):991-999.
[89]Judge AD, Robbins M, Tavakoli I, et al. Confirming the RNAi-mediated mechanism of action of siRNA-based cancer therapeutics in mice[J]. J Clin Invest,2009,119(3):661-673.
[90]Stewart VA, McGrath S, Krieg AM, et al.Activation of innate immunity in healthy Macaca mulatta macaques by a single subcutaneous dose of GMP CpG 7909:safety data and interferon-inducible protein-10 kinetics for humans and macaques[J]. Clin Vaccine Immunol,2008,15(2):221-226.
[91]Vicari AP, Schmalbach T, Lekstrom-Himes J, et al. Safety, pharmacokinetics and immune effects in normal volunteers of CPG 10101 (ACTILON), an investigational synthetic toll-like receptor 9 agonist[J]. Antivir Ther,2007,12(5):741-751.
[92]Goodchild A, Nopper N, King A, et al. Sequence determinants of innate immune activation by short interfering RNAs[J]. BMC Immunol,2009, 10:40.
[93]Monteith DK, Levin AA. Synthetic oligonucleotides:the development of antisense therapeutics[J]. Toxicol Pathol,1999,27(1):8-13.
[94]Chen C, Ridzon DA, Broomer AJ, et al. Realtime quantification of microRNAs by stem-loop RT-PCR[J]. Nucleic Acids Res,2005,33(20):e179.
[95]Rayburn ER, Zhang R. Antisense, RNAi, and gene silencing strategies for therapy:mission possible or impossible[J]?Drug Discov Today,2008,1 3(11-12):513-521.
[96]DeVincenzo J, Cehelsky JE, Alvarez R, et al. Evaluation of the safety, tolerability and pharmacokinetics of ALN-RSV01, a novel RNAi antiviral therapeutic directed against respiratory syncytial virus(RSV) [J]. Antiviral Res, 2008,77(3):225-231.
[97]Jemal A, Siegel R, Ward E, et al. Cancer Statistics,2009[J]. CA Cancer J Clin,2009,59(4):225-249.
[98]Taichman RS, Loberg RD, Mehra R, et al. The evolving biology and treatment of prostate cancer[J]. J Clin Invest,2007,117(9):2351-2361.
[99]Pienta KJ, Loberg R. The "emigration, migration, and immigration" of prostate cancer[J]. Clin Prostate Cancer,2005,4(1):24-30.
[100]Bonecchi R, Galliera E, Borroni EM, et al. Chemokines and chemokine receptors:an overview[J]. Front Biosci,2009,14(1):540-551.
[101]Craig MJ, Loberg RD. CCL2 (Monocyte Chemoattractant Protein-1) in cancer bone metastases[J]. Cancer Metastasis Rev,2006,25(4):611-619.
[102]Roca H, Varsos Z, Pienta KJ. CCL2 protects prostate cancer PC3 cells from autophagic death via phosphatidylinositol 3-kinase/AKT-dependent survivin up-regulation[J]. J Biol Chem,2008,283(36):25057-25073.
[103]Loberg RD, Day LL, Harwood J, et al. CCL2 is a potent regulator of prostate cancer cell migration and proliferation[J]. Neoplasia, 2006,8(7):578-586.
[104]Lu Y, Cai Z, Galson DL, et al. Monocyte chemotactic protein-1 (MCP-1) acts as a paracrine and autocrine factor for prostate cancer growth and invasion[J]. Prostate,2006,66(12):1311-1318.
[105]Loberg RD, Tantivejkul K, Craig M, et al. PAR1-mediated RhoA activation facilitates CCL2-induced chemotaxis in PC-3 cells[J]. J Cell Biochem,2007,101 (5):1292-1300.
[106]van Golen KL, Ying C, Sequeira L, et al. CCL2 induces prostate cancer transendothelial cell migration via activation of the small GTPase Rac[J]. J Cell Biochem,2008,104(5):1587-1597.
[107]Lu Y, Xiao G, Galson DL, et al. PTHrP-induced MCP-1 production by human bone marrow endothelial cells and osteoblasts promotes osteoclast differentiation and prostate cancer cell proliferation and invasion in vitro[J]. Int J Cancer,2007,121 (4):724-733.
[108]Loberg RD, Ying C, Craig M, et al. CCL2 as an important mediator of prostate cancer growth in vivo through the regulation of macrophage infiltration[J]. Neoplasia,2007,9(7):556-562.
[109]Li X, Loberg R, Liao J, et al. A destructive cascade mediated by CCL2 facilitates prostate cancer growth in bone[J]. Cancer Res, 2009,69(4):1685-1692.
[110]Liao J, Li X, Koh AJ, et al. Tumor expressed PTHrP facilitates prostate cancer-induced osteoblastic lesions[J]. Int J Cancer, 2008,123(10):2267-2278.
[111]Lu Y, Cai Z, Xiao G, et al. Monocyte chemotactic protein-1 mediates prostate cancer-induced bone resorption[J]. Cancer Res,2007,6 (8):3646-3653.
[112]Mizutani K, Sud S, Pienta KJ. Prostate cancer promotes CD11b positive cells to differentiate into osteoclasts[J]. J Cell Biochem, 2009,106(4):563-569.
[113]Loberg RD, Ying C, Craig M, et al. Targeting CCL2 with systemic delivery of neutralizing antibodies induces prostate cancer tumor regression in vivo[J]. Cancer Res,2007,67(19):9417-9424.
[114]Lu Y, Chen Q, Corey E, et al. Activation of MCP-1/CCR2 axis promotes prostate cancer growth in bone[J]. Clin Exp Metastasis, 2009,26(2):161-169.
[115]Li X, Qin L, Bergenstock M, et al. Parathyroid hormone stimulates osteoblastic expression of MCP-1 to recruit and increase the fusion of pre/osteoclasts[J]. J Biol Chem,2007,282(45):33098-33106.
[116]Lu Y, Cai Z, Xiao G, et al. CCR2 expression correlates with prostate cancer progression[J]. J Cell Biochem,2007,101 (3):676-685.
[117]Liu J, Shiono J, Shimizu K,et al. Ganoderic acid DM: anti-androgenic osteoclastogenesis inhibitor[J]. Bioorg Med Chem Lett, 2009,19(8):2154-2157.
[118]Wang D, Montgomery RB, Schmidt LJ,et al. Reduced tumor necrosis factor receptor-associated death domain expression is associated with prostate cancer progression[J]. Cancer Res,2009,69(24):9448-9456.
[119]Morrissey C, Kostenuik PL, Brown LG, et al. Host-derived RANKL is responsible for osteolysis in a C4-2 human prostate cancer xenograft model of experimental bone metastases[J]. BMC Cancer,2007,7(8):148-156.
[120]Otsuka S, Hanibuchi M, Ikuta K,et al. A bone metastasis model with osteolytic and osteoblastic properties of human lung cancer AC C-L C-31 9/bone2 in natural killer cell-depleted severe combined im munod eficient mice[J]. Oncol Res,2009,17(11-12):581-591.
[121]Van Sant C, Wang G, Anderson MG,et al. Endothelin signaling in osteoblasts:global genome view and implication of the calcineurin/NFAT path way[J]. Mol Cancer Ther,2007,6(1):253-261.
[122]Muratori C, Mangino G, Affabris E, et al. Astrocytes contacting HIV-1-infected macrophages increase the release of CCL2 in response to the HIV-1-dependent enhancement of membrane-associated TNFa in macrop ha ge s[J]. Glia,2010,58(16):1893-1904.
[123]Rankine EL, Hughes PM, Botham MS, et al. Brain cytokine synthesis induced by an intraparenchymal injection of LPS is reduced in MCP-1-deficient mice prior to leucocyte recruitment[J]. Eur J Neurosci, 2006,24(1):77-86.
[124]Zamara E, Galastri S, Aleffi S, et al. Prevention of severe toxic liver injury and oxidative stress in MCP-1-deficient mice[J]. J Hepatol, 2007,46(2):230-238.
[125]Dogan RN, Elhofy A, Karpus WJ. Production of CCL2 by central nervous system cells regulates development of murine experimental autoimmune encephalomyelitis through the recruitment of TNF- and iNOS-expressing macrophages and myeloid dendritic cells[J]. J Immunol, 2008,180(11):7376-7384.
[126]Held KS, Chen BP, Kuziel WA, et al. Differential roles of CCL2 and CCR2 in host defense to coronavirus infection[J]. Virology, 2004,329(2):251-260.
[127]Dzenko KA, Song L, Ge S, et al. CCR2 expression by brain microvascular endothelial cells is critical for macrophage transendothelial migration in response to CCL2[J]. Microvasc Res,2005,70(1-2):53-64.
[128]Kaplan-Lefko PJ, Chen TM, Ittmann MM, et al. Pathobiology of autochthonous prostate cancer in a pre-clinical transgenic mouse model [J]. Prostate,2003,55(3):219-237.
[129]Balkwill F. Cancer and the chemokine network[J]. Nat Rev Cancer, 2004,4(7):540-550.
[130]Armah HB, Wilson NO, Sarfo BY,et al. Cerebrospinal fluid and serum biomarkers of cerebral malaria mortality in Ghanaian children[J]. Malar J,2007,6:147.
[131]Struyf S, Proost P, Vandercappellen J,et al. Synergistic up-regulation of MCP-2/CCL8 activity is counteracted by chemokine cleavage, limiting its inflammatory and anti-tumoral effects[J]. Eur J Immunol,2009,39(3):843-857.
[132]Kavsak PA, Lee A, Hirte H, et al. Cytokine elevations in acute coronary syndrome and ovarian cancer:a mechanism for the up-regulation of the acute phase proteins in these different disease etiologies[J]. Clin Biochem, 2008,41(7-8):607-610.
[133]Schiller KR, Zillhardt MR, Alley J,et al. Secretion of MCP-1 and other paracrine factors in a novel tumor-bone coculture model [J]. BMC Cancer, 2009,9:45.
[134]Soria G, Yaal-Hahoshen N, Azenshtein E, et al. Concomitant expression of the chemokines RANTES and MCP-1 in human breast cancer:a basis for tumor-promoting interactions[J]. Cytokine,2008,44(1):191-200.
[135]Soria G, Ben-Baruch A. The inflammatory chemokines CCL2 and CCL5 in breast cancer[J]. Cancer Lett,2008,267(2):271-285.
[136]Mestdagt M, Polette M, Buttice G, et al. Transactivation of MCP-1/CCL2 by beta-catenin/TCF-4 in human breast cancer cells[J]. Int J Cancer,2006,118(1):35-42.
[137]Wilson TJ, Nannuru KC, Futakuchi M, et al. Cathepsin G-mediated enhanced TGF-beta signaling promotes angiogenesis via upregulation of VEGF and MCP-1 [J]. Cancer Lett,2010,288(2):162-169.
[138]Isomoto H, Wang A, Nishi Y,et al. Interleukin 8 and 1beta and RANTES levels in esophageal mucosa predict recurrence of endoscopy-negative gastroesophageal reflux disease[J]. Hepato gastroente rology,2008,55(82-83):482-485.
[139]Futagami S, Tatsuguchi A, Hiratsuka T, et al. Monocyte chemoattractant protein 1 and CD40 ligation have a synergistic effect on vascular endothelial growth factor production through cyclooxygenase 2 upregulation in gastric cancer[J]. J Gastroenterol,2008,43(3):216-224.
[140]Perut F, Cenni E, Unger RE, et al. Immunogenic properties of renal cell carcinoma and the pathogenesis of osteolytic bone metastases[J]. Int J Oncol,2009,34(5):1387-1393.
[141]Cai Z, Chen Q, Chen J, et al. Monocyte chemotactic protein 1 promotes lung cancer-induced bone resorptive lesions in vivo[J]. Neoplasia,20 09,11(3):228-236.
[142]Khatri A, Husaini Y, Ow K, et al. Cytosine deaminase-uracil phosphoribosyltransferase and interleukin (IL)-12 and IL-18:a multimodal anticancer interface marked by specific modulation in serum cytokines[J]. Clin Cancer Res,2009,15(7):2323-2334.
[143]Cai Z, Chen Q, Chen J, et al. Monocyte chemotactic protein 1 promotes lung cancer-induced bone resorptive lesions in vivo[J]. Neoplasia, 2009,11(3):228-236.
[144]Wong MP, Cheung KN, Yuen ST, et al. Monocyte chemoattractant protein-1 (MCP-1) expression in primary lymphoepithelioma-like carcinomas (LELCs) of the lung. J Pathol.1998;186(4):372-377.
[145]Niiya M, Niiya K, Kiguchi T, et al. Induction of TNF-alpha, uPA, IL-8 and MCP-1 by doxorubicin in human lung carcinoma cells. Cancer Chemother Pharmacol.2003;52(5):391-398.
[146]Ohkusa T, Yoshida T, Sato N,et al. Commensal bacteria can enter colonic epithelial cells and induce proinflammatory cytokine secretion:a possible pathogenic mechanism of ulcerative colitis[J]. J Med Microbiol, 2009,58(Pt 5):535-545.
[147]Tanaka K, Kurebayashi J, Sohda M, et al. The expression of monocyte chemotactic protein-1 in papillary thyroid carcinoma is correlated with lymph node metastasis and tumor recurrence[J]. Thyroid,2009,19(1):21-25.
[148]Koga M, Kai H, Egami K, et al. Mutant MCP-1 therapy inhibits tumor angiogenesis and growth of malignant melanoma in mice[J]. Biochem Biophys Res Commun,2008,365(2):279-284.
[149]Kong LY, Abou-Ghazal MK, Wei J, et al. A novel inhibitor of signal transducers and activators of transcription 3 activation is efficacious against established central nervous system melanoma and inhibits regulatory T cells[J]. Clin Cancer Res,2008,14(18):5759-5768.
[150]Chavey C, Bibeau F, Gourgou-Bourgade S, et al. Oestrogen receptor negative breast cancers exhibit high cytokine content[J]. Breast Cancer Res, 2007,9(1):R15.
[151]Pacheco-Rodriguez G, Kumaki F, Steagall WK,et al. Chemokine-enhanced chemotaxis of lymphangioleiomyomatosis cells with mutations in the tumor suppressor TSC2 gene[J]. J Immunol, 2009,182(3):1270-1277.
[152]Ueno T, Toi M, Saji H, et al. Significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis, and survival in human breast cancer[J]. Clin Cancer Res,2000,6(8):3282-3289.
[153]Valkovic T, Fuckar D, Stifter S, et al. Macrophage level is not affected by monocyte chemotactic protein-1 in invasive ductal breast carcinoma[J]. J Cancer Res Clin Oncol,2005,131(7):453-458.
[154]Zhang J, Lu Y, Pienta KJ. Multiple roles of chemokine (C-C motif) ligand 2 in promoting prostate cancer growth [J]. J Natl Cancer Inst, 2010,102(8):522-528.
[155]Futagami S, Tatsuguchi A, Hiratsuka T, et al. Monocyte chemoattractant protein 1 and CD40 ligation have a synergistic effect on vascular endothelial growth factor production through cyclooxygenase 2 upregulation in gastric cancer[J]. J Gastroenterol,2008,43(3):216-224.
[156]Kuroda T, Kitadai Y, Tanaka S, et al. Monocyte chemoattractant protein-1 transfection induces angiogenesis and tumorigenesis of gastric carcinoma in nude mice via macrophage recruitment [J]. Clin Cancer Res, 2005,11 (21):7629-7636.
[157]Lukesova S, Kopecky O, Vroblova V, et al. Determination of angiogenic factors in serum by protein array in patients with renal cell carcinoma[J]. Folia Biol (Praha),2008,54(4):134-140.
[158]Bailey C, Negus R, Morris A, et al. Chemokine expression is associated with the accumulation of tumour associated macrophages (TAMs) and progression in human colorectal cancer[J]. Clin Exp Metastasis, 2007,24(2):121-130.
[159]Eisenkraft A, Keidan I, Bielorai B, et al. MCP-1 in the cerebrospinal fluid of children with acute lymphoblastic leukemia[J]. Leuk Res, 2006,30(10):1259-1261.
[160]Mazur G, Wrobel T, Butrym A, et al. Increased monocyte chemoattractant protein 1 (MCP-1/CCL-2) serum level in acute myeloid leukemia[J]. Neoplasma,2007,54(4):285-289.
[161]Arendt BK, Velazquez-Dones A, Tschumper RC, et al. Interleukin 6 induces monocyte chemoattractant protein-1 expression in myeloma cells[J]. Leukemia,2002,16(10):2142-2147.
[162]Johrer K, Janke K, Krugmann J, et al. Transendothelial migration of myeloma cells is increased by tumor necrosis factor (TNF)-alpha via TNF receptor 2 and autocrine up-regulation of MCP-1 [J]. Clin Cancer Res, 2004,10(6):1901-1910.
[163]Vande Broek I, Asosingh K, Vanderkerken K, et al. Chemokine receptor CCR2 is expressed by human multiple myeloma cells and mediates migration to bone marrow stromal cell-produced monocyte chemotactic proteins MCP-1,-2 and -3[J]. Br J Cancer,2003,88(6):855-862.
[164]Pellegrino A, Ria R, Di Pietro G, et al. Bone marrow endothelial cells in multiple myeloma secrete CXC-chemokines that mediate interactions with plasma cells[J]. Br J Haematol,2005,129(2):248-256.
[165]Vanderkerken K, Vande Broek I, Eizirik DL, et al. Monocyte chemoattractant protein-1 (MCP-1), secreted by bone marrow endothelial cells, induces chemoattraction of 5T multiple myeloma cells[J]. Clin Exp Metastasis, 2002,19(1):87-90.
[166]Goede V, Brogelli L, Ziche M, et al. Induction of inflammatory ang iogenesis by monocyte chemoattractant protein-1[J]. Int J Cancer,1999,82(5):765-770.
[167]Hong KH, Ryu J, Han KH. Monocyte chemoattractant protein-1-induced angiogenesis is mediated by vascular endothelial growth factor-A[J]. Blood,2005,105(4):1405-1407.
[168]Cackowski FC, Roodman GD. Perspective on the osteoclast:an angiogenic cell[J]?Ann N Y Acad Sci,2007,1117(11):12-25.
[169]Nam JS, Kang MJ, Suchar AM, et al. Chemokine (C-C motif) ligand 2 mediates the prometastatic effect of dysadherin in human breast cancer cells[J]. Cancer Res,2006,66(14):7176-7184.
[170]Soria G, Yaal-Hahoshen N, Azenshtein E,et al. Concomitant expression of the chemokines RANTES and MCP-1 in human breast cancer:a basis for tumor-promoting interactions[J]. Cytokine,2008,44(1):191-200.
[171]Wang J, Ou ZL, Hou YF, et al. Enhanced expression of Duffy antigen receptor for chemokines by breast cancer cells attenuates growth and metastasis potential [J]. Oncogene,2006,25(54):7201-7211.
[172]Roodman GD, Dougall WC. RANK ligand as a therapeutic target for bone metastases and multiple myeloma[J]. Cancer Treat Rev, 2008,34(1):92-101.
[173]Moon MK, Lee YJ, Kim JS, et al. Effect of caffeic acid on tumor necrosis factor-alpha-induced vascular inflammation in human umbilical vein endothelial cells[J]. Biol Pharm Bull,2009,32(8):1371-1377.
[174]Winterbone MS, Tribolo S, Needs PW,et al. Physiologically relevant metabolites of quercetin have no effect on adhesion molecule or chemokine expression in human vascular smooth muscle cells[J]. Atherosclerosis, 2009,202(2):431-438.
[175]Silvestris F, Cafforio P, Calvani N,et al. Impaired osteoblastogenesis in myeloma bone disease:role of upregulated apoptosis by cytokines and mal ignant plasma cells[J]. Br J Haematol,2004,126(4):475-486.
[176]Dwyer RM, Potter-Beirne SM, Harrington KA, et al. Monocyte chemotactic protein-1 secreted by primary breast tumors stimulates migration of mesenchymal stem cells[J]. Clin Cancer Res,2007,13(17):5020-5027.
[177]Kavsak PA, Lee A, Hirte H, et al. Cytokine elevations in acute coronary syndrome and ovarian cancer:a mechanism for the up-regulation of the acute phase proteins in these different disease etiologies[J].Clin Biochem, 2008,41(7-8):607-610.
[178]Tannock IF, de Wit R, Berry WR, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer[J]. N Engl J Med, 2004,351 (15):1502-1512.
[179]Petrylak DP, Tangen CM, Hussain MH, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer[J]. N Engl J Med,2004,351(15):1513-1520.
[180]Pienta KJ, McGregor N, Axelrod R, et al. Ecological therapy for cancer:defining tumors using an ecosystem paradigm suggests new oppor-tunities for novel cancer treatments [J]. Transl Oncol,2008,1(4):158-164.
[181]Willis A. The ecosystem:an evolving concept viewed historically [J]. Funct Ecol,1997,11(2):268-271.
[182]Kang YS, Song HK, Lee MH,et al.Plasma concentration of visfatin is a new surrogate marker of systemic inflammation in type 2 diabetic patients[J].Diabetes Res Clin Pract,2010,89(2):141-149.
[183]LaMack JA, Himburg HA, Zhang J,et al.Endothelial gene expression in regions of defined shear exposure in the porcine iliac arteries[J].Ann Biomed Eng,2010,38(7):2252-2262.
[184]Datta HK, Ng WF, Walker JA, et al. The cell biology of bone metab olism[J]. J Clin Pathol,2008,61 (5):577-587.
[185]Keller ET, Brown J. Prostate cancer bone metastases promote both osteolytic and osteoblastic activity[J]. J Cell Biochem,2004,91 (4):718-729.
[186]Dougall WC, Chaisson M. The RANK/RANKL/OPG triad in cancer-induced bone diseases[J]. Cancer Metastasis Rev,2006,25(4):541-549.
[187]Roodman GD. Mechanisms of bone metastasis [J]. N Engl J Med,2004,350 (16):1655-1664.
[188]Mizutani K, Sud S, McGregor NA,et al. The chemokine CCL2 increases prostate tumor growth and bone metastasis through macrophage and osteoclast recruitment[J]. Neoplasia,2009,11(11):1235-1242.
[189]Kaur J, Sanyal SN. Diclofenac, a selective COX-2 inhibitor, inhibits DMH-induced colon tumorigenesis through suppression of MCP-1, MIP-1α and VEGF[J].Mol Carcinog,2011,1(25). [Epub ahead of print].
[190]Wang Q, Diao X, Sun J, et al. Regulation of VEGF, MMP-9, and metastasis by CXCR4 in a prostate cancer cell line[J]. Cell Biol Int,2011,2(10). [Epub ahead of print].
[191]Li X,Loberg R,Liao J,et al. A destructive cascade mediated by CCL2 facilitates prostate cancer growth in bone[J]. Cancer Res,2009,69(4):1685-1692.
[192]Kim HY, Choi TW, Kim HJ, et al. A methylene chloride fraction of Saururus chinensis induces apoptosis through the activation of caspase-3 in prostate and breast cancer cells[J]. Phytomedicine,2010,11(24). [Epub ahead of print].
[2]Yin G, Sun Z, Liu N,et al. Production of double-stranded RNA for interference with TMV infection utilizing a bacterial prokaryotic expression system[J]. Appl Microbiol Biotechnol,2009,84(2):323-333.
[3]Craig P, Hunter. Shrinking the black box of RNAi[J]. Current Biology, 2000,10(4):R137-140.
[4]Travis B J. For geneticists, interference becomes an asset[J]. Science News,2000,157(3):36.
[5]Higuchi Y, Kawakami S, Hashida M. Strategies for in vivo delivery of siRNAs:recent progress [J]. BioDrugs,2010,24(3):195-205.
[6]Ketting RF, Haverkamp TH, van Luenen HG, et al. Mut-7 of C. elegans, required for transposon silencing and RNA interference, is a homolog of Werner syndrome helicase and RnaseD[J]. Cell.1999,99(2):133-41.
[7]Dzitoyeva S, Dimitrijevic N, Manev H. Gamma-aminobutyric acid B receptor 1 mediates behavior-impairing actions of alcohol in Drosophila:adult RNA interference and pharmacological evidence[J]. Proc Natl Acad Sci U S A, 2003,100(9):5485-5490.
[8]Gautier EL, Jakubzick C, Randolph GJ. Regulation of the migration and survival of monocyte subsets by chemokine receptors and its relevance to atherosclerosis[J]. Arterioscler Thromb Vasc Biol,2009,29(10):1412-1418.
[9]Lackner P, Kuenz B, Reindl M,et al. Antibodies to myelin oligode ndrocyte glycoprotein in HIV-1 associated neurocognitive disorder:a cross-sectional cohort study[J]. J Neuroinflammation,2010,7:79.
[10]Miyazaki K, Yamasaki N, Oda H,et al. Enhanced expression of p210BCR/ABL and aberrant expression of Zfp423/ZNF423 induce blast crisis of chronic myelogenous leukemia[J]. Blood,2009,113(19):4702-4710.
[11]Rahmani M, Nguyen TK, Dent P,et al. The multikinase inhibitor sorafenib induces apoptosis in highly imatinib mesylate-resistant bcr/abl+ human leukemia cells in association with signal transducer and activator of transcription 5 inhibition and myeloid cell leukemia-1 down-regulation[J]. Mol Pharmacol,2007,72(3):788-795.
[12]Buchert M, Papin M, Bonnans C,et al. Symplekin promotes tumorige nicity by up-regulating claudin-2 expression[J]. Proc Natl Acad Sci U S A,2010,107(6):2628-2633.
[13]Futami M, Hatano T, Soda Y, et al. RNAi-mediated silencing of p190Bcr-Abl inactivates Stat5 and cooperates with imatinib mesylate and 17-allylamino-17-demetoxygeldanamycin in selective killing of p190 Bcr-A bl-expressing leukemia cells[J]. Leukemia,2008,22(6):1131-1138.
[14]Zhang X, Li J, Qiu Z, et al. Co-suppression of MDR1 (multidrug resistance 1) and GCS (glucosylceramide synthase) restores sensitivity to multidrug resistance breast cancer cells by RNA interference (RNAi)[J]. Cancer Biol Ther,2009,8(12):1117-1121.
[15]Song E, Lee SK, Wang J, et al. RNA interference targeting Fas protects mice from fulminant hepatitis[J]. Nat Med,2003,9(3):347-351.
[16]Zender L, Hutker S, Liedtke C, et al.Caspase 8 small interfering RNA prevents acute liver failure in mice[J]. Proc Natl Acad Sci USA, 2003,100(13):7797-7802.
[17]Ullu E, Tschudi C, Chakraborty T. RNA interference in protozoan parasites[J]. Cell Microbiol,2004,6(6):509-519.
[18]Jolly C, Booth NJ, Neil SJ. Cell-cell spread of human immunodeficiency virus type 1 overcomes tetherin/BST-2-mediated restriction in T cells[J].J Virol,2010,84(23):12185-12199.
[19]von Eije KJ, ter Brake O, Berkhout B. Human immunodeficiency virus type 1 escape is restricted when conserved genome sequences are targeted by RNA interference[J]. J Virol,2008,82(6):2895-2903.
[20]Wang FX, Huang J, Zhang H,et al. APOBEC3G upregulation by alpha interferon restricts human immunodeficiency virus type 1 infection in human peripheral plasmacytoid dendritic cells[J]. J Gen Virol,2008,89(Pt 3):722-730.
[21]Turner AM, De La Cruz J, Morris KV. Mobilization-competent Lentiviral Vector-mediated Sustained Transcriptional Modulation of HIV-1 Expression[J]. Mol Ther,2009,17(2):360-368.
[22]von Eije KJ, ter Brake O, Berkhout B. Stringent testing identifies highly potent and escape-proof anti-HIV short hairpin RNAs[J]. J Gene Med, 2009,11(6):459-467.
[23]Nishi J, Minamino T, Miyauchi H,et al. Vascular endothelial growth factor receptor-1 regulates postnatal angiogenesis through inhibition of the excessive activation of Akt[J]. Circ Res,2008,103(3):261-268.
[24]Takeda A, Tsukuda M, Mizumoto H,et al. A plant RNA virus suppresses RNA silencing through viral RNA replication[J]. EMBO J,2005,2 4(17):3147-3157.
[25]Agrawal L, Maxwell CR, Peters PJ,et al. Complexity in human immunodeficiency virus type 1 (HIV-1) co-receptor usage:roles of CCR3 and CCR5 in HIV-1 infection of monocyte-derived macrophages and brain mic rog lia[J]. J Gen Virol,2009,90(Pt 3):710-722.
[26]Zamore PD. Plant RNAi:how a viral silencing suppressor inactivates siRNA[J]. Curr Biol,2004,14(5):198-200.
[27]Rakhshandehroo F, Takeshita M, Squires J,et al. The influence of RNA-dependent RNA polymerase 1 on potato virus Y infection and on other antiviral response genes[J]. Mol Plant Microbe Interact,2009,22(10):1312-1318.
[28]Delgadillo MO, Saenz P, Salvador B,et al. Human influenza virus NS1 protein enhances viral pathogenicity and acts as an RNA silencing suppr essor in plants[J]. J Gen Virol,2004,85(4):993-999.
[29]Bucher E, Hemmes H, de Haan P,et al. The influenza A virus NS1 pro tein binds small interfering RNAs and suppresses RNA silencing in pla nts[J]. J Gen Virol,2004,85(4):983-991.
[30]Li WX, Li H, Lu R, et al. Interferon antagonist proteins of influenza and vaccinia viruses are suppressors of RNA silencing[J].Proc Natl Acad Sci U SA,2004,101(5):1350-1355.
[31]Dickson ME, Tian X, Liu X, et al. Synthetic microRNA designed to target glioma-associated antigen 1 transcription factor inhibits division and induces late apoptosis in pancreatic tumor cells[J]. Clin Cancer Res, 2006,12(21):6557-6564.
[32]Klunker S, Chong MM, Mantel PY, et al. Transcription factors RUNX1 and RUNX3 in the induction and suppressive function of Foxp3+ inducible regulatory T cells[J]. J Exp Med,2009,206(12):2701-2715.
[33]Li Y, Zhao M, Yin H, et al. Overexpression of the growth arrest and DNA damage-induced 45alpha gene contributes to autoimmunity by promoting DNA demethylation in lupus T cells[J]. Arthritis Rheum,2010,62(5):1438-1447.
[34]Farina F, Alberti A, Breuil N, et al. Differential expression pattern of the four mitochondrial adenine nucleotide transporter ant genes and their roles during the development of Caenorhabditis elegans[J]. Dev Dyn,2008,23 7(6):1668-1681.
[35]McAllister CS, Samuel CE. The RNA-activated protein kinase enhances the induction of interferon-beta and apoptosis mediated by cytop las mic RNA sensors[J]. J Biol Chem,2009,284(3):1644-1651.
[36]Ely A, Naidoo T, Arbuthnot P. Efficient silencing of gene expression with modular trimeric Pol Ⅱ expression cassettes comprising microRNA shutt les[J]. Nucleic Acids Res,2009,37(13):e91.
[37]Lee SK, Li W, Ryu SE,et al. Vacuolar (H+)-ATPases in Caenorh abditis elegans:what can we learn about giant H+pumps from tiny worms[J]? Biochim Biophys Acta,2010,1797(10):1687-1695.
[38]Wang G, Reinke V. A C. elegans Piwi, PRG-1, regulates 21U-RNAs during spermatogenesis[J]. Curr Biol,2008,18(12):861-867.
[39]Marchais A, Bohn C, Bouloc P, et al. RsaOG, a new staphylococcal family of highly transcribed non-coding RNA[J]. RNA Biol, 2010,7(2):116-119.
[40]Alcazar RM, Lin R, Fire AZ. Transmission dynamics of heritable silencing induced by double-stranded RNA in Caenorhabditis elegans[J]. Genetics,2008,180(3):1275-1288.
[41]Kennerdell JR, Carthew RW.Use of dsRNA-mediated genetic interference to demonstrate that frizzled and frizzled 2 act in the wingless pathway[J]. Cell,1998,95(7):1017-1026.
[42]von Eije KJ, ter Brake O, Berkhout B. Stringent testing identifies highly potent and escape-proof anti-HIV short hairpin RNAs[J]. J Gene Med, 2009,11(6):459-467.
[43]de Fougerolles A, Vornlocher HP, Maraganore J, et al. Interfering with disease:a progress report on siRNA-based therapeutics[J]. Nat Rev Drug Discov,2007,6(6):443-453.
[44]Swayze EE, Bhat B. Antisense Drug Technologies, Principles, Strategies and Applications[M].2nd ed. New York:Taylor and Francis Group,2008.
[45]Haussecker D. The business of RNAi therapeutics [J]. Hum Gene Ther, 2008,19(5):451-462.
[46]Novobrantseva TI, Akinc A, Borodovsky A, et al. Delivering silence: advancements in developing siRNA therapeutics[J]. Curr Opin Drug Discov Devel,2008, 11(2):217-224.
[47]Whitehead KA, Langer R, Anderson DG. Knocking down barriers:advances in siRNA delivery[J]. Nat Rev Drug Discov,2009, 8(2):129-138.
[48]Bitko V, Musiyenko A, Shulyayeva O, et al. Inhibition of respiratory viruses by nasally administered siRNA[J]. Nat Med,2005,11(1):50-55.
[49]Alvarez R, Elbashir S, Borland T, et al.RNA interference-mediated silencing of the respiratory syncytial virus nucleocapsid defines a potent anti viral strategy[J]. Antimicrob Agents Chemother,2009,53(9):3952-3962.
[50]Palliser D, Chowdhury D, Wang QY, et al. An siRNA-based microbicide protects mice from lethal herpes simplex virus 2 infection[J]. Nat u re,2006,439(7072):89-94.
[51]Querbes W, Ge P, Zhang W, et al. Direct CNS delivery of siRNA mediates robust silencing in oligodendrocytes[J]. Oligonucleotides,2009,1 9(1):23-30.
[52]Kleinman ME, Yamada K, Takeda A, et al. Sequence-and target-independent angiogenesis suppression by siRNA via TLR3[J]. Nature, 2008,452(7187):591-597.
[53]Shen J, Samul R, Silva RL, et al. Suppression of ocular neovascularization with siRNA targeting VEGF receptor 1 [J]. Gene Ther,2006, 13(3):225-234.
[54]Soutschek J, Akinc A, Bramlage B, et al.Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs[J]. Nature, 2004,432(7014):173-178.
[55]Wolfrum C, Shi S, Jayaprakash KN, et al. Mechanisms and optimiz ation of in vivo delivery of lipophilic siRNAs[J]. Nat Biotechnol,2007, 25(10):1149-1157.
[56]Morrissey DV, Lockridge JA, Shaw L, et al.Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs[J]. Nat Biotechnol,20 05,23(8):1002-1007.
[57]Zimmermann TS, Lee AC, Akinc A,et al.RNAi-mediated gene silencing in non-human primates[J]. Nature,2006,441(7089):111-114.
[58]Abrams MT, Koser ML, Seitzer J, et al.Evaluation of efficacy, biodistribution, and inflammation for a potent siRNA nanoparticle:effect of dexamethasone cotreatment[J]. Mol Ther,2010,18(1):171-180.
[59]Akinc A, Querbes W, De S, et al.Targeted Delivery of RNAi Therap eutics With Endogenous and Exogenous Ligand-Based Mechanisms [J]. Mol Ther,2010,18(7):1357-1364.
[60]Rozema DB, Lewis DL, Wakefield DH, et al.Dynamic polyconjugates for targeted in vivo delivery of siRNA to hepatocytes[J]. Proc Natl Acad Sci U SA,2007,104(32):12982-12987.
[61]Bartlett DW, Su H, Hildebrandt IJ, et al. Impact of tumorspecific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging[J]. Proc Natl Acad Sci USA,2007, 104(39):15549-15554.
[62]Semple SC, Akinc A, Chen J, et al. Rational design of cationic lipids for siRNA delivery[J]. Nat Biotechnol,2010,28(2):172-176.
[63]Frank-Kamenetsky M, Grefhorst A, Anderson NN, et al. Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates[J]. Proc Natl Acad Sci USA,2008, 105(33):11915-11920.
[64]Akinc A, Goldberg M, Qin J, et al. Development of lipidoid siRNA formulations for systemic delivery to the liver[J]. Mol Ther, 2009,17(5):872-879.
[65]Love KT, Mahon KP, Levins CG, et al. Lipid-like materials for low-dose, in vivo gene silencing[J].Proc Natl Acad Sci USA,2010, 107(5):1864-1869.
[66]Judge AD, Robbins M, Tavakoli I, et al. Confirming the RNAi-mediated mechanism of action of siRNA-based cancer therapeutics in mice[J]. J Clin Invest,2009,119(3):661-673.
[67]Song E, Zhu P, Lee SK, et al.Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors[J]. Nat Biotechnol,2005, 23(6):709-717.
[68]Peer D, Zhu P, Carman CV, et al.Selective gene silencing in activated leukocytes by targeting siRNAs to the integrin lymphocyte function-associated antigen-1[J]. Proc Natl Acad Sci USA,2007,104(10):4095-4100.
[69]Peer D, Park EJ, Morishita Y, et al.Systemic leukocytedirected siRNA delivery revealing cyclin Dl as an anti-inflammatory target[J]. Science,2008, 319(5863):627-630.
[70]Aouadi M, Tesz GJ, Nicoloro SM, et al.Orally delivered siRNA targeting macrophage Map4k4 suppresses systemic inflammation[J]. Nature, 2009,458(7242):1180-1184.
[71]Jackson AL, Linsley PS. Recognizing and avoiding siRNA off-target effects for target identification and therapeutic application[J]. Nat Rev Drug Discov,2010,9(1):57-67.
[72]Jackson AL, Bartz SR, Schelter J,et al. Expression profiling reveals off-target gene regulation by RNAi[J]. Nat Biotechnol,2003,21(6):635-637.
[73]Jackson AL, Burchard J, Schelter J, et al.Widespread siRNA "off-target" transcript silencing mediated by seed region sequence complem entarity[J]. RNA,2006(7),12:1179-1187.
[74]Birmingham A, Anderson EM, Reynolds A,et al.3'UTR seed matches, but not overall identity, are associated with RNAi off-targets [J]. Nat Methods,2006,3:199-204.
[75]Grimm D, Streetz KL, Jopling CL, et al.Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways[J]. Nature, 2006,441(7092):537-541.
[76]Khan AA, Betel D, Miller ML, et al. Transfection of small RNAs globally perturbs gene regulation by endogenous microRNAs[J]. Nat Biotec hn ol,2009,27(6):549-555.
[77]Hornung V, Guenthner-Biller M, Bourquin C, et al.Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7[J]. Nat Med,2005,11(3):263-270.
[78]Judge AD, Sood V, Shaw JR, et al.Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA[J]. Nat Biotechnol, 2005,23(4):457-642.
[79]Sioud M. Induction of inflammatory cytokines and interferon responses by double-stranded and single-stranded siRNAs is sequence-depen dent and requires endosomal localization[J]. J Mol Biol,2005,348(5):1079-1090.
[80]Aleman LM, Doench J, Sharp PA. Comparison of siRNA-induced offtarget RNA and protein effects[J]. RNA,2007,13(3):385-395.
[81]Bilanges B, Stokoe D. Direct comparison of the specificity of gene silencing using antisense oligonucleotides and RNAi[J]. Biochem J,2005, 388(2):573-583.
[82]Fisher AA, Ye D, Sergueev DS, et al. Evaluating the specificity of antisense oligonucleotide conjugates. A DNA array analysis[J]. J Biol Chem, 2002,277(25):22980-22984.
[83]Irwin RD, Parker JS, Lobenhofer EK,et al. Transcriptional profiling of the left and median liver lobes of male f344/n rats following exposure to acetaminophen[J]. Toxicol Pathol,2005,33(1):111-1117.
[84]Lin Z, Crockett DK, Jenson SD,et al. Quantitative proteomic and transcriptional analysis of the response to the p38 mitogen-activated protein kinase inhibitor SB2035380 in transformed follicular lymphoma cells[J]. Mol Cell Proteomics,2004,3(8):820-833.
[85]Robbins M, Judge A, MacLachlan I. siRNA and innate immunity[J]. Oligonucleotides,2009,19(2):89-102.
[86]Yoneyama M, Kikuchi M, Natsukawa T, et al. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiv iral responses[J].Nat Immunol,2004,5(7):730-737.
[87]Korth MJ, Lyons CN, Wambach M,et al. Cloning, expression, and cellular localization of the oncogenic 58-kDa inhibitor of the RNA-activated human and mouse protein kinase[J]. Gene,1996,170(2):181-188.
[88]Robbins M, Judge A, Ambegia E, et al. Misinterpreting the therapeutic effects of small interfering RNA caused by immune stimulation[J]. Hum Gene Ther,2008,19(10):991-999.
[89]Judge AD, Robbins M, Tavakoli I, et al. Confirming the RNAi-mediated mechanism of action of siRNA-based cancer therapeutics in mice[J]. J Clin Invest,2009,119(3):661-673.
[90]Stewart VA, McGrath S, Krieg AM, et al.Activation of innate immunity in healthy Macaca mulatta macaques by a single subcutaneous dose of GMP CpG 7909:safety data and interferon-inducible protein-10 kinetics for humans and macaques[J]. Clin Vaccine Immunol,2008,15(2):221-226.
[91]Vicari AP, Schmalbach T, Lekstrom-Himes J, et al. Safety, pharmacokinetics and immune effects in normal volunteers of CPG 10101 (ACTILON), an investigational synthetic toll-like receptor 9 agonist[J]. Antivir Ther,2007,12(5):741-751.
[92]Goodchild A, Nopper N, King A, et al. Sequence determinants of innate immune activation by short interfering RNAs[J]. BMC Immunol,2009, 10:40.
[93]Monteith DK, Levin AA. Synthetic oligonucleotides:the development of antisense therapeutics[J]. Toxicol Pathol,1999,27(1):8-13.
[94]Chen C, Ridzon DA, Broomer AJ, et al. Realtime quantification of microRNAs by stem-loop RT-PCR[J]. Nucleic Acids Res,2005,33(20):e179.
[95]Rayburn ER, Zhang R. Antisense, RNAi, and gene silencing strategies for therapy:mission possible or impossible[J]?Drug Discov Today,2008,1 3(11-12):513-521.
[96]DeVincenzo J, Cehelsky JE, Alvarez R, et al. Evaluation of the safety, tolerability and pharmacokinetics of ALN-RSV01, a novel RNAi antiviral therapeutic directed against respiratory syncytial virus(RSV) [J]. Antiviral Res, 2008,77(3):225-231.
[97]Jemal A, Siegel R, Ward E, et al. Cancer Statistics,2009[J]. CA Cancer J Clin,2009,59(4):225-249.
[98]Taichman RS, Loberg RD, Mehra R, et al. The evolving biology and treatment of prostate cancer[J]. J Clin Invest,2007,117(9):2351-2361.
[99]Pienta KJ, Loberg R. The "emigration, migration, and immigration" of prostate cancer[J]. Clin Prostate Cancer,2005,4(1):24-30.
[100]Bonecchi R, Galliera E, Borroni EM, et al. Chemokines and chemokine receptors:an overview[J]. Front Biosci,2009,14(1):540-551.
[101]Craig MJ, Loberg RD. CCL2 (Monocyte Chemoattractant Protein-1) in cancer bone metastases[J]. Cancer Metastasis Rev,2006,25(4):611-619.
[102]Roca H, Varsos Z, Pienta KJ. CCL2 protects prostate cancer PC3 cells from autophagic death via phosphatidylinositol 3-kinase/AKT-dependent survivin up-regulation[J]. J Biol Chem,2008,283(36):25057-25073.
[103]Loberg RD, Day LL, Harwood J, et al. CCL2 is a potent regulator of prostate cancer cell migration and proliferation[J]. Neoplasia, 2006,8(7):578-586.
[104]Lu Y, Cai Z, Galson DL, et al. Monocyte chemotactic protein-1 (MCP-1) acts as a paracrine and autocrine factor for prostate cancer growth and invasion[J]. Prostate,2006,66(12):1311-1318.
[105]Loberg RD, Tantivejkul K, Craig M, et al. PAR1-mediated RhoA activation facilitates CCL2-induced chemotaxis in PC-3 cells[J]. J Cell Biochem,2007,101 (5):1292-1300.
[106]van Golen KL, Ying C, Sequeira L, et al. CCL2 induces prostate cancer transendothelial cell migration via activation of the small GTPase Rac[J]. J Cell Biochem,2008,104(5):1587-1597.
[107]Lu Y, Xiao G, Galson DL, et al. PTHrP-induced MCP-1 production by human bone marrow endothelial cells and osteoblasts promotes osteoclast differentiation and prostate cancer cell proliferation and invasion in vitro[J]. Int J Cancer,2007,121 (4):724-733.
[108]Loberg RD, Ying C, Craig M, et al. CCL2 as an important mediator of prostate cancer growth in vivo through the regulation of macrophage infiltration[J]. Neoplasia,2007,9(7):556-562.
[109]Li X, Loberg R, Liao J, et al. A destructive cascade mediated by CCL2 facilitates prostate cancer growth in bone[J]. Cancer Res, 2009,69(4):1685-1692.
[110]Liao J, Li X, Koh AJ, et al. Tumor expressed PTHrP facilitates prostate cancer-induced osteoblastic lesions[J]. Int J Cancer, 2008,123(10):2267-2278.
[111]Lu Y, Cai Z, Xiao G, et al. Monocyte chemotactic protein-1 mediates prostate cancer-induced bone resorption[J]. Cancer Res,2007,6 (8):3646-3653.
[112]Mizutani K, Sud S, Pienta KJ. Prostate cancer promotes CD11b positive cells to differentiate into osteoclasts[J]. J Cell Biochem, 2009,106(4):563-569.
[113]Loberg RD, Ying C, Craig M, et al. Targeting CCL2 with systemic delivery of neutralizing antibodies induces prostate cancer tumor regression in vivo[J]. Cancer Res,2007,67(19):9417-9424.
[114]Lu Y, Chen Q, Corey E, et al. Activation of MCP-1/CCR2 axis promotes prostate cancer growth in bone[J]. Clin Exp Metastasis, 2009,26(2):161-169.
[115]Li X, Qin L, Bergenstock M, et al. Parathyroid hormone stimulates osteoblastic expression of MCP-1 to recruit and increase the fusion of pre/osteoclasts[J]. J Biol Chem,2007,282(45):33098-33106.
[116]Lu Y, Cai Z, Xiao G, et al. CCR2 expression correlates with prostate cancer progression[J]. J Cell Biochem,2007,101 (3):676-685.
[117]Liu J, Shiono J, Shimizu K,et al. Ganoderic acid DM: anti-androgenic osteoclastogenesis inhibitor[J]. Bioorg Med Chem Lett, 2009,19(8):2154-2157.
[118]Wang D, Montgomery RB, Schmidt LJ,et al. Reduced tumor necrosis factor receptor-associated death domain expression is associated with prostate cancer progression[J]. Cancer Res,2009,69(24):9448-9456.
[119]Morrissey C, Kostenuik PL, Brown LG, et al. Host-derived RANKL is responsible for osteolysis in a C4-2 human prostate cancer xenograft model of experimental bone metastases[J]. BMC Cancer,2007,7(8):148-156.
[120]Otsuka S, Hanibuchi M, Ikuta K,et al. A bone metastasis model with osteolytic and osteoblastic properties of human lung cancer AC C-L C-31 9/bone2 in natural killer cell-depleted severe combined im munod eficient mice[J]. Oncol Res,2009,17(11-12):581-591.
[121]Van Sant C, Wang G, Anderson MG,et al. Endothelin signaling in osteoblasts:global genome view and implication of the calcineurin/NFAT path way[J]. Mol Cancer Ther,2007,6(1):253-261.
[122]Muratori C, Mangino G, Affabris E, et al. Astrocytes contacting HIV-1-infected macrophages increase the release of CCL2 in response to the HIV-1-dependent enhancement of membrane-associated TNFa in macrop ha ge s[J]. Glia,2010,58(16):1893-1904.
[123]Rankine EL, Hughes PM, Botham MS, et al. Brain cytokine synthesis induced by an intraparenchymal injection of LPS is reduced in MCP-1-deficient mice prior to leucocyte recruitment[J]. Eur J Neurosci, 2006,24(1):77-86.
[124]Zamara E, Galastri S, Aleffi S, et al. Prevention of severe toxic liver injury and oxidative stress in MCP-1-deficient mice[J]. J Hepatol, 2007,46(2):230-238.
[125]Dogan RN, Elhofy A, Karpus WJ. Production of CCL2 by central nervous system cells regulates development of murine experimental autoimmune encephalomyelitis through the recruitment of TNF- and iNOS-expressing macrophages and myeloid dendritic cells[J]. J Immunol, 2008,180(11):7376-7384.
[126]Held KS, Chen BP, Kuziel WA, et al. Differential roles of CCL2 and CCR2 in host defense to coronavirus infection[J]. Virology, 2004,329(2):251-260.
[127]Dzenko KA, Song L, Ge S, et al. CCR2 expression by brain microvascular endothelial cells is critical for macrophage transendothelial migration in response to CCL2[J]. Microvasc Res,2005,70(1-2):53-64.
[128]Kaplan-Lefko PJ, Chen TM, Ittmann MM, et al. Pathobiology of autochthonous prostate cancer in a pre-clinical transgenic mouse model [J]. Prostate,2003,55(3):219-237.
[129]Balkwill F. Cancer and the chemokine network[J]. Nat Rev Cancer, 2004,4(7):540-550.
[130]Armah HB, Wilson NO, Sarfo BY,et al. Cerebrospinal fluid and serum biomarkers of cerebral malaria mortality in Ghanaian children[J]. Malar J,2007,6:147.
[131]Struyf S, Proost P, Vandercappellen J,et al. Synergistic up-regulation of MCP-2/CCL8 activity is counteracted by chemokine cleavage, limiting its inflammatory and anti-tumoral effects[J]. Eur J Immunol,2009,39(3):843-857.
[132]Kavsak PA, Lee A, Hirte H, et al. Cytokine elevations in acute coronary syndrome and ovarian cancer:a mechanism for the up-regulation of the acute phase proteins in these different disease etiologies[J]. Clin Biochem, 2008,41(7-8):607-610.
[133]Schiller KR, Zillhardt MR, Alley J,et al. Secretion of MCP-1 and other paracrine factors in a novel tumor-bone coculture model [J]. BMC Cancer, 2009,9:45.
[134]Soria G, Yaal-Hahoshen N, Azenshtein E, et al. Concomitant expression of the chemokines RANTES and MCP-1 in human breast cancer:a basis for tumor-promoting interactions[J]. Cytokine,2008,44(1):191-200.
[135]Soria G, Ben-Baruch A. The inflammatory chemokines CCL2 and CCL5 in breast cancer[J]. Cancer Lett,2008,267(2):271-285.
[136]Mestdagt M, Polette M, Buttice G, et al. Transactivation of MCP-1/CCL2 by beta-catenin/TCF-4 in human breast cancer cells[J]. Int J Cancer,2006,118(1):35-42.
[137]Wilson TJ, Nannuru KC, Futakuchi M, et al. Cathepsin G-mediated enhanced TGF-beta signaling promotes angiogenesis via upregulation of VEGF and MCP-1 [J]. Cancer Lett,2010,288(2):162-169.
[138]Isomoto H, Wang A, Nishi Y,et al. Interleukin 8 and 1beta and RANTES levels in esophageal mucosa predict recurrence of endoscopy-negative gastroesophageal reflux disease[J]. Hepato gastroente rology,2008,55(82-83):482-485.
[139]Futagami S, Tatsuguchi A, Hiratsuka T, et al. Monocyte chemoattractant protein 1 and CD40 ligation have a synergistic effect on vascular endothelial growth factor production through cyclooxygenase 2 upregulation in gastric cancer[J]. J Gastroenterol,2008,43(3):216-224.
[140]Perut F, Cenni E, Unger RE, et al. Immunogenic properties of renal cell carcinoma and the pathogenesis of osteolytic bone metastases[J]. Int J Oncol,2009,34(5):1387-1393.
[141]Cai Z, Chen Q, Chen J, et al. Monocyte chemotactic protein 1 promotes lung cancer-induced bone resorptive lesions in vivo[J]. Neoplasia,20 09,11(3):228-236.
[142]Khatri A, Husaini Y, Ow K, et al. Cytosine deaminase-uracil phosphoribosyltransferase and interleukin (IL)-12 and IL-18:a multimodal anticancer interface marked by specific modulation in serum cytokines[J]. Clin Cancer Res,2009,15(7):2323-2334.
[143]Cai Z, Chen Q, Chen J, et al. Monocyte chemotactic protein 1 promotes lung cancer-induced bone resorptive lesions in vivo[J]. Neoplasia, 2009,11(3):228-236.
[144]Wong MP, Cheung KN, Yuen ST, et al. Monocyte chemoattractant protein-1 (MCP-1) expression in primary lymphoepithelioma-like carcinomas (LELCs) of the lung. J Pathol.1998;186(4):372-377.
[145]Niiya M, Niiya K, Kiguchi T, et al. Induction of TNF-alpha, uPA, IL-8 and MCP-1 by doxorubicin in human lung carcinoma cells. Cancer Chemother Pharmacol.2003;52(5):391-398.
[146]Ohkusa T, Yoshida T, Sato N,et al. Commensal bacteria can enter colonic epithelial cells and induce proinflammatory cytokine secretion:a possible pathogenic mechanism of ulcerative colitis[J]. J Med Microbiol, 2009,58(Pt 5):535-545.
[147]Tanaka K, Kurebayashi J, Sohda M, et al. The expression of monocyte chemotactic protein-1 in papillary thyroid carcinoma is correlated with lymph node metastasis and tumor recurrence[J]. Thyroid,2009,19(1):21-25.
[148]Koga M, Kai H, Egami K, et al. Mutant MCP-1 therapy inhibits tumor angiogenesis and growth of malignant melanoma in mice[J]. Biochem Biophys Res Commun,2008,365(2):279-284.
[149]Kong LY, Abou-Ghazal MK, Wei J, et al. A novel inhibitor of signal transducers and activators of transcription 3 activation is efficacious against established central nervous system melanoma and inhibits regulatory T cells[J]. Clin Cancer Res,2008,14(18):5759-5768.
[150]Chavey C, Bibeau F, Gourgou-Bourgade S, et al. Oestrogen receptor negative breast cancers exhibit high cytokine content[J]. Breast Cancer Res, 2007,9(1):R15.
[151]Pacheco-Rodriguez G, Kumaki F, Steagall WK,et al. Chemokine-enhanced chemotaxis of lymphangioleiomyomatosis cells with mutations in the tumor suppressor TSC2 gene[J]. J Immunol, 2009,182(3):1270-1277.
[152]Ueno T, Toi M, Saji H, et al. Significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis, and survival in human breast cancer[J]. Clin Cancer Res,2000,6(8):3282-3289.
[153]Valkovic T, Fuckar D, Stifter S, et al. Macrophage level is not affected by monocyte chemotactic protein-1 in invasive ductal breast carcinoma[J]. J Cancer Res Clin Oncol,2005,131(7):453-458.
[154]Zhang J, Lu Y, Pienta KJ. Multiple roles of chemokine (C-C motif) ligand 2 in promoting prostate cancer growth [J]. J Natl Cancer Inst, 2010,102(8):522-528.
[155]Futagami S, Tatsuguchi A, Hiratsuka T, et al. Monocyte chemoattractant protein 1 and CD40 ligation have a synergistic effect on vascular endothelial growth factor production through cyclooxygenase 2 upregulation in gastric cancer[J]. J Gastroenterol,2008,43(3):216-224.
[156]Kuroda T, Kitadai Y, Tanaka S, et al. Monocyte chemoattractant protein-1 transfection induces angiogenesis and tumorigenesis of gastric carcinoma in nude mice via macrophage recruitment [J]. Clin Cancer Res, 2005,11 (21):7629-7636.
[157]Lukesova S, Kopecky O, Vroblova V, et al. Determination of angiogenic factors in serum by protein array in patients with renal cell carcinoma[J]. Folia Biol (Praha),2008,54(4):134-140.
[158]Bailey C, Negus R, Morris A, et al. Chemokine expression is associated with the accumulation of tumour associated macrophages (TAMs) and progression in human colorectal cancer[J]. Clin Exp Metastasis, 2007,24(2):121-130.
[159]Eisenkraft A, Keidan I, Bielorai B, et al. MCP-1 in the cerebrospinal fluid of children with acute lymphoblastic leukemia[J]. Leuk Res, 2006,30(10):1259-1261.
[160]Mazur G, Wrobel T, Butrym A, et al. Increased monocyte chemoattractant protein 1 (MCP-1/CCL-2) serum level in acute myeloid leukemia[J]. Neoplasma,2007,54(4):285-289.
[161]Arendt BK, Velazquez-Dones A, Tschumper RC, et al. Interleukin 6 induces monocyte chemoattractant protein-1 expression in myeloma cells[J]. Leukemia,2002,16(10):2142-2147.
[162]Johrer K, Janke K, Krugmann J, et al. Transendothelial migration of myeloma cells is increased by tumor necrosis factor (TNF)-alpha via TNF receptor 2 and autocrine up-regulation of MCP-1 [J]. Clin Cancer Res, 2004,10(6):1901-1910.
[163]Vande Broek I, Asosingh K, Vanderkerken K, et al. Chemokine receptor CCR2 is expressed by human multiple myeloma cells and mediates migration to bone marrow stromal cell-produced monocyte chemotactic proteins MCP-1,-2 and -3[J]. Br J Cancer,2003,88(6):855-862.
[164]Pellegrino A, Ria R, Di Pietro G, et al. Bone marrow endothelial cells in multiple myeloma secrete CXC-chemokines that mediate interactions with plasma cells[J]. Br J Haematol,2005,129(2):248-256.
[165]Vanderkerken K, Vande Broek I, Eizirik DL, et al. Monocyte chemoattractant protein-1 (MCP-1), secreted by bone marrow endothelial cells, induces chemoattraction of 5T multiple myeloma cells[J]. Clin Exp Metastasis, 2002,19(1):87-90.
[166]Goede V, Brogelli L, Ziche M, et al. Induction of inflammatory ang iogenesis by monocyte chemoattractant protein-1[J]. Int J Cancer,1999,82(5):765-770.
[167]Hong KH, Ryu J, Han KH. Monocyte chemoattractant protein-1-induced angiogenesis is mediated by vascular endothelial growth factor-A[J]. Blood,2005,105(4):1405-1407.
[168]Cackowski FC, Roodman GD. Perspective on the osteoclast:an angiogenic cell[J]?Ann N Y Acad Sci,2007,1117(11):12-25.
[169]Nam JS, Kang MJ, Suchar AM, et al. Chemokine (C-C motif) ligand 2 mediates the prometastatic effect of dysadherin in human breast cancer cells[J]. Cancer Res,2006,66(14):7176-7184.
[170]Soria G, Yaal-Hahoshen N, Azenshtein E,et al. Concomitant expression of the chemokines RANTES and MCP-1 in human breast cancer:a basis for tumor-promoting interactions[J]. Cytokine,2008,44(1):191-200.
[171]Wang J, Ou ZL, Hou YF, et al. Enhanced expression of Duffy antigen receptor for chemokines by breast cancer cells attenuates growth and metastasis potential [J]. Oncogene,2006,25(54):7201-7211.
[172]Roodman GD, Dougall WC. RANK ligand as a therapeutic target for bone metastases and multiple myeloma[J]. Cancer Treat Rev, 2008,34(1):92-101.
[173]Moon MK, Lee YJ, Kim JS, et al. Effect of caffeic acid on tumor necrosis factor-alpha-induced vascular inflammation in human umbilical vein endothelial cells[J]. Biol Pharm Bull,2009,32(8):1371-1377.
[174]Winterbone MS, Tribolo S, Needs PW,et al. Physiologically relevant metabolites of quercetin have no effect on adhesion molecule or chemokine expression in human vascular smooth muscle cells[J]. Atherosclerosis, 2009,202(2):431-438.
[175]Silvestris F, Cafforio P, Calvani N,et al. Impaired osteoblastogenesis in myeloma bone disease:role of upregulated apoptosis by cytokines and mal ignant plasma cells[J]. Br J Haematol,2004,126(4):475-486.
[176]Dwyer RM, Potter-Beirne SM, Harrington KA, et al. Monocyte chemotactic protein-1 secreted by primary breast tumors stimulates migration of mesenchymal stem cells[J]. Clin Cancer Res,2007,13(17):5020-5027.
[177]Kavsak PA, Lee A, Hirte H, et al. Cytokine elevations in acute coronary syndrome and ovarian cancer:a mechanism for the up-regulation of the acute phase proteins in these different disease etiologies[J].Clin Biochem, 2008,41(7-8):607-610.
[178]Tannock IF, de Wit R, Berry WR, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer[J]. N Engl J Med, 2004,351 (15):1502-1512.
[179]Petrylak DP, Tangen CM, Hussain MH, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer[J]. N Engl J Med,2004,351(15):1513-1520.
[180]Pienta KJ, McGregor N, Axelrod R, et al. Ecological therapy for cancer:defining tumors using an ecosystem paradigm suggests new oppor-tunities for novel cancer treatments [J]. Transl Oncol,2008,1(4):158-164.
[181]Willis A. The ecosystem:an evolving concept viewed historically [J]. Funct Ecol,1997,11(2):268-271.
[182]Kang YS, Song HK, Lee MH,et al.Plasma concentration of visfatin is a new surrogate marker of systemic inflammation in type 2 diabetic patients[J].Diabetes Res Clin Pract,2010,89(2):141-149.
[183]LaMack JA, Himburg HA, Zhang J,et al.Endothelial gene expression in regions of defined shear exposure in the porcine iliac arteries[J].Ann Biomed Eng,2010,38(7):2252-2262.
[184]Datta HK, Ng WF, Walker JA, et al. The cell biology of bone metab olism[J]. J Clin Pathol,2008,61 (5):577-587.
[185]Keller ET, Brown J. Prostate cancer bone metastases promote both osteolytic and osteoblastic activity[J]. J Cell Biochem,2004,91 (4):718-729.
[186]Dougall WC, Chaisson M. The RANK/RANKL/OPG triad in cancer-induced bone diseases[J]. Cancer Metastasis Rev,2006,25(4):541-549.
[187]Roodman GD. Mechanisms of bone metastasis [J]. N Engl J Med,2004,350 (16):1655-1664.
[188]Mizutani K, Sud S, McGregor NA,et al. The chemokine CCL2 increases prostate tumor growth and bone metastasis through macrophage and osteoclast recruitment[J]. Neoplasia,2009,11(11):1235-1242.
[189]Kaur J, Sanyal SN. Diclofenac, a selective COX-2 inhibitor, inhibits DMH-induced colon tumorigenesis through suppression of MCP-1, MIP-1α and VEGF[J].Mol Carcinog,2011,1(25). [Epub ahead of print].
[190]Wang Q, Diao X, Sun J, et al. Regulation of VEGF, MMP-9, and metastasis by CXCR4 in a prostate cancer cell line[J]. Cell Biol Int,2011,2(10). [Epub ahead of print].
[191]Li X,Loberg R,Liao J,et al. A destructive cascade mediated by CCL2 facilitates prostate cancer growth in bone[J]. Cancer Res,2009,69(4):1685-1692.
[192]Kim HY, Choi TW, Kim HJ, et al. A methylene chloride fraction of Saururus chinensis induces apoptosis through the activation of caspase-3 in prostate and breast cancer cells[J]. Phytomedicine,2010,11(24). [Epub ahead of print].