抗TfR抗体偶联物靶向抗瘤效应及其杂交瘤细胞株轻链基因分析
|
摘要
[目的]
本课题设计将姜黄素作为抗肿瘤药物在光照条件下激发成为光敏剂,通过修饰后偶联特异性的抗TfR抗体协同发挥双向抗癌效应。为了延长药物的半衰期,进一步探索姜黄素的光学特性,比较了TfR抗体与光敏剂联合应用的不同方法,检测其偶联效率及体外功能,探讨作用机制,并据此设计制备纳米化中药光敏剂-抗TfR单抗偶联物,为肿瘤的多重定位显像与靶向治疗提供实验依据。在此基础上还分析了从同一杂交瘤细胞株中扩增出的三条轻链基因,为实现抗TfR基因工程改造与基因工程抗体靶向偶联物抗瘤效应研究奠定基础。
[方法]
1.抗TfR单抗-偶联物的制备及其抗瘤效应测定
(1)研究姜黄素光敏特性及荧光显微镜观察肝癌细胞内吞Cur；
(2)以碳二亚胺为缩合剂制备Cur-Ab免疫偶联物,间接ELISA测定偶联物抗体效价,MTT法测定其IC50；
(3)光敏化姜黄素-抗TfR单抗靶向性纳米粒的制备及效应测定：
1)薄膜法和注入法制备脂质体,色谱法测定其包峰率；
2) TfR mAb修饰的姜黄素脂质体的制备；
3)扫描电镜观测脂质体姜黄素外形及粒径大小；
4)FCM检测Cur-NP-PEG-Ab与肝癌细胞的结合率；
5)FCM检测Cur-NP-PEG-Ab在光照和非光照情况下对肝癌细胞增殖/凋亡,周期等的影响；
6)分别由DCFH-DA荧光探针和罗丹明染色试剂盒检测线粒体电位和细胞活性氧的变化。
2.抗TfR单抗轻链基因分析
(1)采用PCR法从分泌抗TfR单抗杂交瘤细胞中扩增抗体可变区序列；
(2)通过IMGT和NCBI数据库在线分析VH和VL基因序列；
(3)经由Insight II软件模拟抗TfR单抗Fabs段分子结构。
[结果]
1.抗TfR单抗-偶联物的制备及其抗瘤效应
(1)普通光照对细胞培养无影响,姜黄素在电镜下能发出土黄色荧光,在灯光照射下对肿瘤细胞原有的杀伤作用增强,荧光显微镜下可见Cur能被肝癌细胞内吞；
(2)化学偶联法制备的抗TfR单抗-姜黄素偶联物,其抗体效价较单抗有所降低,但对HepG2肝癌细胞的杀伤作用比姜黄素或抗TfR单抗单独作用时明显增强,与姜黄素+单抗混合物杀伤作用类似；
(3)光敏化姜黄素-抗TfR单抗靶向性纳米粒的性质、特征均符合纳米级颗粒：
1)薄膜分散法制备的脂质体包封率稳定；
2)扫描电镜显示Cur-NP-PEG-Ab形态稳定,属于纳米级；
3)FCM分析结果表明Cur-NP-PEG-Ab与鼠源单抗具有相似的结合率；
4)FCM分析结果表明在光照条件下Cur-NP-PEG-Ab能影响肝癌细胞的周期S期,并促进其凋亡；
5) Cur-NP-PEG-Ab使线粒体电位降低和活性氧产生增加。
2.抗TfR抗体基因分析
在分泌抗TfR单克隆抗体的同一株杂交瘤细胞中扩增出三条轻链和一条有功能的重链可变区基因,功能性的VH基因片段经DNA凝胶电泳鉴定片段大小与理论值414bp相符,DNA测序显示该基因有完整阅读框架。得到的三条轻链通过IMGT和NCBI分析确认均来自于不同的基因家族：VL-fl引物扩增得到MOPC21骨髓瘤中的非功能内源性轻链;由VL-f2引物扩增出有功能的轻链基因(命名为Vκ2),属于IGKV4-59*0 1家族,可变区长318bp,信号肽长66bp；由VL-f3引物扩增出的功能性轻链基因(命名为Vκ3),属于IGKV6-17*01,可变区长324bp,信号肽长60bp。NCBI数据库报道Vκ3序列与许多单抗轻链可变区相同,也与骨髓瘤MPC11有功能的重排等位基因完全匹配。3D分子模拟显示根据TfR单抗可变区模拟的Fabs结构,两条不同轻链和同一重链偶联制备的Fabs段都具有完整的功能域和结合凹槽。
[结论]
本研究通过制备可生物降解的mPEG-PLGA-CUR-NPs纳米颗粒,并通过体外实验初步研究了改造的纳米粒生物学作用,获得了有意义的研究结果,研究表明：①制备的Cur-NP-PEG-Ab纳米粒符合纳米级别,具有较高的载药量和包封率；②Cur-NP-PEG-Ab与靶细胞结合率和亲本鼠源性抗体与HepG2细胞结合率相近；③Cur-NP-PEG-Ab在光照下对肿瘤细胞杀伤作用明显增强,提示该纳米粒在完成靶向杀伤肿瘤的同时,能发挥光敏剂的效应；④首次将Cur-NP-PEG-Ab中的姜黄素作为中药光敏剂,脂质体包裹的姜黄素纳米粒,能在体内发挥延长代谢的作用,经过体内循环后,脱去脂质体外衣的姜黄素,又能接着发挥中药本身的抗癌效应。并在此基础上分析了从同一杂交瘤细胞株中扩增出的三条轻链基因,为进一步抗体改造奠定了基础。
The project designed to take curcumin as anti-cancer drug and photosensitizer in the light condition. We conjugated modified-curcimin with anti-TfR antibody collaborative to cure cancer. In order to extend drug half-life, to further explore the optical properties of curcumin, we compared different conjugate methods of antibody in combination with the photosensitizer and assessed the coupling efficiency and in vitro testing, discussed the mechanism. Based on the former research, we constructed nano- curcumin and anti-TfR monoclonal antibody conjugate. This work gave experimental evidence for multiple tumor imaging and targeted therapy. Based on analysis of three light chains from the same hybridoma which serecting against TfR mAb, the efforts lay solid foundation for the realization of genetically engineered and genetic engineering targeted anti-tumor effect.
[Methods]
1. Fabricate and assessment the conjugate of antibody and curcumin.
(1) Evaluated tumor cells growth condition in light/non-light by cell count, and determined tumor cell killing effect of photosensitizatied curcumin. Fluorescence microscope to observe HepG2 cells endocytose curcumin.
(2) Depended on carbodiimide as the condensing agent, preparated Cur-Ab immunoconjugate chemical, calculated conjugates'antibody titers by indirect ELISA assessed their IC50 by the MTT method.
(3) Preparation photosensitizated curcumin-anti-TfR monoclonal antibody actively nanoparticles and preliminary assessment its functions.
1) With a thin film and the injection method to prepare liposomes, and assessed the peak rate of packets.
2) Modified curcumin liposomes with TfR mAb.
3) Particle morphology studied using scanning electron microscopy.
4) FCM detection Cur-NP-PEG-Ab binding rate with cancer cells.
5) FCM detection Cur-NP-PEG-Ab in the light and non-light situations on proliferation/apoptosis, cell cycles, etc.
6) Used DCFH-DA and ROS kits to assess the changes of mitochondrial potential and ROS.
2. Analysis the variable chains of TfR antibody.
(1) PCR amplification of VL and VH genes from hybridoma which secertin anti-TfR antibody.
(2) Cloning and sequencing of the VH and VL gene by IMGT and NCBI database.
(3) Molecular modeling by Insight II to simulate Fabs of against TfR mAb.
[Results]
1. Fabricated and assessed anti-tumor effect of the conjugate of antibody and curcumin.
(1) Normal white light had no effect on cell culture, curcumin can emission khaki-colored fluorescence by electron microscopy, and curcumin killing tumor cells power will be greatly enhanced in the light irradiation, and Curcumin had been endocytosed by HepG2 cells.
(2) Coupled of anti-TfR monoclonal antibody and curcumin conjugate in chemical method, the conjugate's antibody titer decreased. But the killing activity of conjugate super than curcumin, anti-TfR monoclonal antibody on hepatocellular carcinoma cells the killing effect was similar to curcumin+antibody mixture.
(3) Active targeted nanoparticles of photosensitizated curcumin conjugate anti-TfR monoclonal antibody characteristics are in line with nano-level:
1) The liposome encapsulation has higher stability by film dispersion method.
2) Scanning electron microscopy showed that Cur-NP-PEG-Ab form stable, belonging to nano-level.
3) FCM showed that Cur-NP-PEG-Ab has similar binding capacity with the parental murine monoclonal antibody.
4) FCM detected under illumination condition, Cur-NP-PEG-Ab can affect hepatoma cells cycle, and promoted their apoptosis.
5) Cur-NP-PEG-Ab impacted on mitochondrial potential and ROS, made mitochondrial potential decreased and higher ROS.
2. Analysis the variable chains of TfR antibody.
Amplified VH and VL genes of anti-TfR monoclonal antibody by PCR, the fragment size in line with the theoretical value, DNA sequencing also showed their are correct sequences. We got the functional light chain different from the former result, belonged to IGKV6-17*01 family has 324bp, and 60bp signal. In order to ensure the accuracy of tests, we tried several amplifications and sequence analyses, confirmed that the light chain was amplified by the primer VL-f3, and the previous sequence in line with VL-f2 primer. So we use a single primer amplification, respectively. We got three different light chain genes from one hybridoma: non-functional endogenous light chain of MOPC21 amplified byVL-fl primers; the primer VL-f2 amplified the variable VL genes was classified to IGKV4-59*01 family has 318bp, and 66bp signal peptide; the primer VL-f3 hybridized the sequence is not the same as in previous one, belonging to different family. Molecular simulation showed the Fabs of the two functional light chains and heavy chain both have binding grooves。
[Conclusions]
This study was prepared biodegradable mPEG-PLGA-CUR-NPs nanoparticles and preliminary studied the modified nanoparticles biological effects in vitro, obtained meaningful results, studies demonstrated that:(1)Preparation of the Cur-NP-PEG-Ab nanoparticles with high drug loading and encapsulation efficiency complied the nano-level; (2)Cur-NP-PEG-Ab had similar binding rate with target cells (HepG2) to the parental murine antibody; (3)Cur-NP-PEG-Ab enhanced tumor cell killing effect significantly in the light, suggesting that the nanoparticles in the completion of target killing of tumor, can play as a photosensitizer at the same time;
(4)the paper first time reported that curcumin in the Cur-NP-PEG-Ab as a herb photosensitizer, liposome-modified-curcumin nanoparticles can play longer in the body metabolism, and after circulated through the body, curcumin coated off liposomes, can then play their anti-cancer effects of Chinese medicine. Based on this analysis of here light chain genes from the same hybridoma, and laid the foundation for the transformation of antibodies.
本课题设计将姜黄素作为抗肿瘤药物在光照条件下激发成为光敏剂,通过修饰后偶联特异性的抗TfR抗体协同发挥双向抗癌效应。为了延长药物的半衰期,进一步探索姜黄素的光学特性,比较了TfR抗体与光敏剂联合应用的不同方法,检测其偶联效率及体外功能,探讨作用机制,并据此设计制备纳米化中药光敏剂-抗TfR单抗偶联物,为肿瘤的多重定位显像与靶向治疗提供实验依据。在此基础上还分析了从同一杂交瘤细胞株中扩增出的三条轻链基因,为实现抗TfR基因工程改造与基因工程抗体靶向偶联物抗瘤效应研究奠定基础。
[方法]
1.抗TfR单抗-偶联物的制备及其抗瘤效应测定
(1)研究姜黄素光敏特性及荧光显微镜观察肝癌细胞内吞Cur；
(2)以碳二亚胺为缩合剂制备Cur-Ab免疫偶联物,间接ELISA测定偶联物抗体效价,MTT法测定其IC50；
(3)光敏化姜黄素-抗TfR单抗靶向性纳米粒的制备及效应测定：
1)薄膜法和注入法制备脂质体,色谱法测定其包峰率；
2) TfR mAb修饰的姜黄素脂质体的制备；
3)扫描电镜观测脂质体姜黄素外形及粒径大小；
4)FCM检测Cur-NP-PEG-Ab与肝癌细胞的结合率；
5)FCM检测Cur-NP-PEG-Ab在光照和非光照情况下对肝癌细胞增殖/凋亡,周期等的影响；
6)分别由DCFH-DA荧光探针和罗丹明染色试剂盒检测线粒体电位和细胞活性氧的变化。
2.抗TfR单抗轻链基因分析
(1)采用PCR法从分泌抗TfR单抗杂交瘤细胞中扩增抗体可变区序列；
(2)通过IMGT和NCBI数据库在线分析VH和VL基因序列；
(3)经由Insight II软件模拟抗TfR单抗Fabs段分子结构。
[结果]
1.抗TfR单抗-偶联物的制备及其抗瘤效应
(1)普通光照对细胞培养无影响,姜黄素在电镜下能发出土黄色荧光,在灯光照射下对肿瘤细胞原有的杀伤作用增强,荧光显微镜下可见Cur能被肝癌细胞内吞；
(2)化学偶联法制备的抗TfR单抗-姜黄素偶联物,其抗体效价较单抗有所降低,但对HepG2肝癌细胞的杀伤作用比姜黄素或抗TfR单抗单独作用时明显增强,与姜黄素+单抗混合物杀伤作用类似；
(3)光敏化姜黄素-抗TfR单抗靶向性纳米粒的性质、特征均符合纳米级颗粒：
1)薄膜分散法制备的脂质体包封率稳定；
2)扫描电镜显示Cur-NP-PEG-Ab形态稳定,属于纳米级；
3)FCM分析结果表明Cur-NP-PEG-Ab与鼠源单抗具有相似的结合率；
4)FCM分析结果表明在光照条件下Cur-NP-PEG-Ab能影响肝癌细胞的周期S期,并促进其凋亡；
5) Cur-NP-PEG-Ab使线粒体电位降低和活性氧产生增加。
2.抗TfR抗体基因分析
在分泌抗TfR单克隆抗体的同一株杂交瘤细胞中扩增出三条轻链和一条有功能的重链可变区基因,功能性的VH基因片段经DNA凝胶电泳鉴定片段大小与理论值414bp相符,DNA测序显示该基因有完整阅读框架。得到的三条轻链通过IMGT和NCBI分析确认均来自于不同的基因家族：VL-fl引物扩增得到MOPC21骨髓瘤中的非功能内源性轻链;由VL-f2引物扩增出有功能的轻链基因(命名为Vκ2),属于IGKV4-59*0 1家族,可变区长318bp,信号肽长66bp；由VL-f3引物扩增出的功能性轻链基因(命名为Vκ3),属于IGKV6-17*01,可变区长324bp,信号肽长60bp。NCBI数据库报道Vκ3序列与许多单抗轻链可变区相同,也与骨髓瘤MPC11有功能的重排等位基因完全匹配。3D分子模拟显示根据TfR单抗可变区模拟的Fabs结构,两条不同轻链和同一重链偶联制备的Fabs段都具有完整的功能域和结合凹槽。
[结论]
本研究通过制备可生物降解的mPEG-PLGA-CUR-NPs纳米颗粒,并通过体外实验初步研究了改造的纳米粒生物学作用,获得了有意义的研究结果,研究表明：①制备的Cur-NP-PEG-Ab纳米粒符合纳米级别,具有较高的载药量和包封率；②Cur-NP-PEG-Ab与靶细胞结合率和亲本鼠源性抗体与HepG2细胞结合率相近；③Cur-NP-PEG-Ab在光照下对肿瘤细胞杀伤作用明显增强,提示该纳米粒在完成靶向杀伤肿瘤的同时,能发挥光敏剂的效应；④首次将Cur-NP-PEG-Ab中的姜黄素作为中药光敏剂,脂质体包裹的姜黄素纳米粒,能在体内发挥延长代谢的作用,经过体内循环后,脱去脂质体外衣的姜黄素,又能接着发挥中药本身的抗癌效应。并在此基础上分析了从同一杂交瘤细胞株中扩增出的三条轻链基因,为进一步抗体改造奠定了基础。
The project designed to take curcumin as anti-cancer drug and photosensitizer in the light condition. We conjugated modified-curcimin with anti-TfR antibody collaborative to cure cancer. In order to extend drug half-life, to further explore the optical properties of curcumin, we compared different conjugate methods of antibody in combination with the photosensitizer and assessed the coupling efficiency and in vitro testing, discussed the mechanism. Based on the former research, we constructed nano- curcumin and anti-TfR monoclonal antibody conjugate. This work gave experimental evidence for multiple tumor imaging and targeted therapy. Based on analysis of three light chains from the same hybridoma which serecting against TfR mAb, the efforts lay solid foundation for the realization of genetically engineered and genetic engineering targeted anti-tumor effect.
[Methods]
1. Fabricate and assessment the conjugate of antibody and curcumin.
(1) Evaluated tumor cells growth condition in light/non-light by cell count, and determined tumor cell killing effect of photosensitizatied curcumin. Fluorescence microscope to observe HepG2 cells endocytose curcumin.
(2) Depended on carbodiimide as the condensing agent, preparated Cur-Ab immunoconjugate chemical, calculated conjugates'antibody titers by indirect ELISA assessed their IC50 by the MTT method.
(3) Preparation photosensitizated curcumin-anti-TfR monoclonal antibody actively nanoparticles and preliminary assessment its functions.
1) With a thin film and the injection method to prepare liposomes, and assessed the peak rate of packets.
2) Modified curcumin liposomes with TfR mAb.
3) Particle morphology studied using scanning electron microscopy.
4) FCM detection Cur-NP-PEG-Ab binding rate with cancer cells.
5) FCM detection Cur-NP-PEG-Ab in the light and non-light situations on proliferation/apoptosis, cell cycles, etc.
6) Used DCFH-DA and ROS kits to assess the changes of mitochondrial potential and ROS.
2. Analysis the variable chains of TfR antibody.
(1) PCR amplification of VL and VH genes from hybridoma which secertin anti-TfR antibody.
(2) Cloning and sequencing of the VH and VL gene by IMGT and NCBI database.
(3) Molecular modeling by Insight II to simulate Fabs of against TfR mAb.
[Results]
1. Fabricated and assessed anti-tumor effect of the conjugate of antibody and curcumin.
(1) Normal white light had no effect on cell culture, curcumin can emission khaki-colored fluorescence by electron microscopy, and curcumin killing tumor cells power will be greatly enhanced in the light irradiation, and Curcumin had been endocytosed by HepG2 cells.
(2) Coupled of anti-TfR monoclonal antibody and curcumin conjugate in chemical method, the conjugate's antibody titer decreased. But the killing activity of conjugate super than curcumin, anti-TfR monoclonal antibody on hepatocellular carcinoma cells the killing effect was similar to curcumin+antibody mixture.
(3) Active targeted nanoparticles of photosensitizated curcumin conjugate anti-TfR monoclonal antibody characteristics are in line with nano-level:
1) The liposome encapsulation has higher stability by film dispersion method.
2) Scanning electron microscopy showed that Cur-NP-PEG-Ab form stable, belonging to nano-level.
3) FCM showed that Cur-NP-PEG-Ab has similar binding capacity with the parental murine monoclonal antibody.
4) FCM detected under illumination condition, Cur-NP-PEG-Ab can affect hepatoma cells cycle, and promoted their apoptosis.
5) Cur-NP-PEG-Ab impacted on mitochondrial potential and ROS, made mitochondrial potential decreased and higher ROS.
2. Analysis the variable chains of TfR antibody.
Amplified VH and VL genes of anti-TfR monoclonal antibody by PCR, the fragment size in line with the theoretical value, DNA sequencing also showed their are correct sequences. We got the functional light chain different from the former result, belonged to IGKV6-17*01 family has 324bp, and 60bp signal. In order to ensure the accuracy of tests, we tried several amplifications and sequence analyses, confirmed that the light chain was amplified by the primer VL-f3, and the previous sequence in line with VL-f2 primer. So we use a single primer amplification, respectively. We got three different light chain genes from one hybridoma: non-functional endogenous light chain of MOPC21 amplified byVL-fl primers; the primer VL-f2 amplified the variable VL genes was classified to IGKV4-59*01 family has 318bp, and 66bp signal peptide; the primer VL-f3 hybridized the sequence is not the same as in previous one, belonging to different family. Molecular simulation showed the Fabs of the two functional light chains and heavy chain both have binding grooves。
[Conclusions]
This study was prepared biodegradable mPEG-PLGA-CUR-NPs nanoparticles and preliminary studied the modified nanoparticles biological effects in vitro, obtained meaningful results, studies demonstrated that:(1)Preparation of the Cur-NP-PEG-Ab nanoparticles with high drug loading and encapsulation efficiency complied the nano-level; (2)Cur-NP-PEG-Ab had similar binding rate with target cells (HepG2) to the parental murine antibody; (3)Cur-NP-PEG-Ab enhanced tumor cell killing effect significantly in the light, suggesting that the nanoparticles in the completion of target killing of tumor, can play as a photosensitizer at the same time;
(4)the paper first time reported that curcumin in the Cur-NP-PEG-Ab as a herb photosensitizer, liposome-modified-curcumin nanoparticles can play longer in the body metabolism, and after circulated through the body, curcumin coated off liposomes, can then play their anti-cancer effects of Chinese medicine. Based on this analysis of here light chain genes from the same hybridoma, and laid the foundation for the transformation of antibodies.
引文
1.李健,李凤,庞爱芝,冯秀艳,姜黄素对Hela细胞周期各时相的影响,吉林大学学报(医学版),2006年04期。
2.厉红元,车艺,汤为学,姜黄素对人肝癌细胞增殖和凋亡的影响,中华肝脏病杂志,2002年06期。
3.薛妍,夏天,赵建斌,吴少华,张仲海,王宗仁,姜黄素对人肝癌细胞SMMC-7721的抑制作用,第四军医大学学报2000年第21卷第5期。
4.王牡,阮余霞,彭元,陈伟,蔡继业,姜黄素对人肝癌HepG2细胞毒性的分析。
5.王伟章,张碧鱼,陈宏远,张黎,姜黄素对人肝癌细胞Sk-Hep-1抗癌作用的研究[J].中国中药杂志,2010,35(4)：485.
6.郑丽端,童强松,吴翠环,曾甫清,姜黄素诱导卵巢癌细胞系A2780细胞周期阻滞和凋亡,华中科技大学学报(医学版)
7.施文荣,张振林,刘艳,光照对姜黄素诱导人乳腺癌MCF-7细胞凋亡的影响,广东医学院学报,2009年第27卷第二期。
8.蒋福升,徐秀玲,金波,陈铌铍,高承贤,丁志山,吕圭源,水溶性姜黄素前药制备及其体外抗肿瘤实验研究,中国药学杂志,2009年10月第44卷第19期。
9.曾霞波,夏新蜀,余和平,白定群,谭勇,何勇,许川山,光敏化姜黄素对人乳腺癌细胞的抑制作用,激光杂志,2008年第29卷第2期。
10.陈瑞川,苏金华,马胜平,蒋雪玄,霍霞,光敏化姜黄素诱导胃癌细胞凋亡,癌症,2000年第19卷第4期。
11.王伟章,张碧鱼,袁健,毛建文,梅文杰,姜黄素对肝癌细胞JAK-STAT信号通路的影响,药学学报,2009,44,1434-1439。
12.曹军,姜丽平,耿成燕,姚晓峰,仲来福,活性氧在姜黄素对人胚肾293细胞细胞毒性中的作用,毒理学杂志,2009年8月第23卷第4期。
13. Zhang Z, Cao W, Jin H, Lovell JF, Yang M, Ding L, Chen J, Corbin I, Luo Q, Zheng G, Biomimetic nanocarrier for direct cytosolic drug delivery.Angew Chem Int Ed Engl.2009; 48,9171-5.
14. Zhang Z, Chen J, Ding L, Jin H, Lovell JF, Corbin IR, Cao W, Lo PC, Yang M, Tsao MS, Luo Q, Zheng G, HDL-mimicking peptide-lipid nanoparticles with improved tumor targeting. Small.2010,6,430-7.
15. Jiao Y, Wilkinson J 4th, Di X, Wang W, Hatcher H, Kock ND D'Agostino R Jr, Knovich MA, Torti FM, Torti SV. Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator. Blood.2009,113, 462-9.
16. Gururajan M, Dasu T, Shahidain S, Jennings CD, Robertson DA, Rangnekar VM, Bondada S, Spleen tyrosine kinase (Syk), a novel target of curcumin, is required for B lymphoma growth.J Immunol.2007,178,111-21.
17. Egan ME, Pearson M, Weiner SA, Rajendran V, Rubin D, Glockner-Pagel J, Canny S, Du K, Lukacs GL, Caplan MJ., Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects.Science.2004,304,600-2.
18. Zhang M, Murakami T, Ajima K, Tsuchida K, Sandanayaka AS, Ito O, Iijima S, Yudasaka M., Fabrication of ZnPc/protein nanohorns for double photodynamic and hyperthermic cancer phototherapy. Proc Natl Acad Sci U S A.2008,105, 14773-8.
19. Weitman SD, Weinberg AG, Coney LR, Zurawski VR, Jennings DS, Kamen BA., Cellular localization of the folate receptor:potential role in drug toxicity and folate homeostasis. Cancer Res.1992,52,6708-11.
20. Weitman SD, Weinberg AG, Coney LR, Zurawski VR, Jennings DS, Kamen BA., Cellular localization of the folate receptor:potential role in drug toxicity and folate homeostasis. Cancer Res.1992,52,6708-11.
21.陈昆,李文新,激光纳米治疗癌症研究发现新途径,中国激光,2005,32,12,1698.
22. O'Neal DP, Hirsch LR, Halas NJ, Payne JD, West JL, Photo-thermal tumor ablation in mice using near infrared-absorbing nanoparticles. Cancer Lett.2004, 209,171-6.
23. Overgaard J., The current and potential role of hyperthermia in radiotherapy.Int J Radiat Oncol Biol Phys.1989 16,535-49.
24.邱海霞,刘凡光,顾瑛,肿瘤光动力学疗法免疫机制的研究进展,中国激光医学杂志,2005,14,105-113.
25. Korbelik M, Dougherty GJ., Photodynamic therapy-mediated immune response against subcutaneous mouse tumors.Cancer Res.1999,59,1941-6.
26. Zhang H, Ma W, Li Y., Generation of effective vaccines against liver cancer by using photodynamic therapy.Lasers Med Sci.2009,24,549-52
27. Preise D, Oren R, Glinert I, Kalchenko V, Jung S, Scherz A, Salomon Y. Systemic antitumor protection by vascular-targeted photodynamic therapy involves cellular and humoral immunity. Cancer Immunol Immunother.2009,58, 71-84.
28. Korbelik M, Sun J., Photodynamic therapy-generated vaccine for cancer therapy. Cancer Immunol Immunother.2006,55,900-9.
29. Vonarx V, Foultier MT, Anasagasti L, Morlet L, Lajat Y, Patrice T. Photodynamic effect on the specific antitumor immune activity. Int J Immunopharmacol.1997,19,101-10.
30. Krosl G, Korbelik M, Krosl J, Dougherty GJ., Potentiation of photodynamic therapy-elicited antitumor response by localized treatment with granulocyte-macrophage colony-stimulating factor.Cancer Res.1996,56,3281-6.
31. Sanoj Rejinold N, Sreerekha PR, Chennazhi KP, Nair SV, Jayakumar R., Biocompatible, biodegradable and thermo-sensitive chitosan-g-poly (N-isopropylacrylamide) nanocarrier for curcumin drug delivery.Int J Biol Macromol.2011, Apr 22.
32. Sasaki H, Sunagawa Y, Takahashi K, Imaizumi A, Fukuda H, Hashimoto T, Wada H, Katanasaka Y, Kakeya H, Fujita M, Hasegawa K, Morimoto T., Innovative preparation of curcumin for improved oral bioavailability.Biol Pharm Bull.2011, 34,660-5.
33. Reuter S, Gupta SC, Park B, Goel A, Aggarwal BB., Epigenetic changes induced by curcumin and other natural compounds.Genes Nutr.2011, Apr 24.
34. Katsori AM, Chatzopoulou M, Dimas K, Kontogiorgis C, Patsilinakos A, Trangas T, Hadjipavlou-Litina D., Curcumin analogues as possible anti-proliferative & anti-inflammatory agents. Eur J Med Chem.2011, Apr 5.
35. Qian H, Yang Y, Wang X., Curcumin enhanced adriamycin-induced human liver-derived Hepatoma G2 cell death through activation of mitochondria-mediated apoptosis and autophagy. Eur J Pharm Sci.2011, Apr 14
36. Zhang H, Zhang L, Yuan P, Wang C., Preparation and in vitro release characteristics of curcumin in nanosuspensions. Zhongguo Zhong Yao Za Zhi. 2011,36,132-5.
37. Darvesh AS, Aggarwal BB, Bishayee A., Curcumin and Liver Cancer:A Review.Curr Pharm Biotechnol.2011, Apr 5.
38. Lee YJ, Kim NY, Suh YA, Lee C., Involvement of ROS in Curcumin-induced Autophagic Cell Death. Korean J Physiol Pharmacol.2011,15,1-7.
39. Hegde ML, Hegde PM, Rao KS, Mitra S., Oxidative genome damage and its repair in neurodegenerative diseases:function of transition metals as a double-edged sword.J Alzheimers Dis.2011,4,183-98.
40. Sanphui P, Goud NR, Khandavilli UB, Bhanoth S, Nangia A., New polymorphs of curcumin. Chem Commun (Camb).2011,47,5013-5.
41. Griesser M, Pistis V, Suzuki T, Tejera N, Pratt DA, Schneider C., Autoxidative and cyclooxygenase-2 catalyzed transformation of the dietary chemopreventive agent curcumin. J Biol Chem.2011,286,1114-24.
1. Arnold, K., L. Bordoli. J Kopp. and T. Schwede.2006. The SWISS-MODEL Workspace:A web-based environment for protein structure homology modelling. Bioinformatics.22:195-201.
2. Barderas, R., J. Desmet. P. Timmerman. R. Meloen. and J.I.Casal.2008. Affinity maturation of antibodies assisted by in silico modeling. Proc Natl Acad Sci U S A.105:9029-9034.
3. Blatt, N.B., R.M. Bill. and G.D. Glick.1998. Characterization of a unique anti-DNA hybridoma. Hybridoma 17:33-39.
4. Benkert, P., M. Biasini. and T.Schwede.2011. Toward the estimation of the absolute quality of individual protein structure models. Bioinformatics, 27:343-350.
5. Bose, B., and S. Sinha.2005. Problems in using statistical analysis of replacement and silent mutations in antibody genes for determining antigen-driven affinity selection. Immunology 116:172-183
6. Brochet, X., M.P.Lefranc. and V. Giudicelli.2008. IMGT/V-QUEST:the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysis. Nucl. Acids Res.36:503-508.
7. Carey, J.B., C.S. Moffatt-Blue. L.C. Watson. A.L. Gavin. and A.J. Feeney. 2008. Repertoire-based selection into the marginal zone compartment during B cell development. J. Exp. Med.205:2043-2052.
8. Carroll,W.L., E.Mendel. and S. Levy.1988. Hybridoma fusion cell lines contain an aberrant kappa transcript. Mol. Immunol.25:991.
9. Chang, B. and P. Casali.1994. The CDR1 sequences of a major proportion of human germline Ig VH genes are inherently susceptible to amino acid replacement. Immunol Today.15:367-373.
10. Chemin. G., A. Tinguely. C. Sirac. F. Lechouane. S. Duchez. M. Cogne. and L.Delpy.2010. Multiple RNA surveillance mechanisms cooperate to reduce the amount of nonfunctional Ig kappa transcripts. J Immunol.184:5009-5017.
11. Chen, C., V.A. Roberts.and M. B. Rittenberg.1992. Generation and analusis of random point mutations in an antibody CDR2 sequence:many mutated antibodies lose their ability to bind antigen. J.Exp.Med.176:855-866.
12. Chen, D., K. Altmann. P.J. Hanna. A. Tammer.and J.R. Underwood. 1997.Detection of two isotypically different antibodies produced by a murine hybridoma. Hybridoma 16:195-199.
13. Diaw, L., D. Siwarski. W. DuBois. G. Jones. and K. Huppi.2000. Double producers of kappa and lambda define a subset of B cells in mouse plasmacytomas. Mol Immunol.37:775-781.
14. Guex, N. and M. C. Peitsch.1997. SWISS-MODEL and the Swiss-PdbViewer: An environment for comparative protein modelling. Electrophoresis.18: 2714-2723.
15. Hawley, R.G., M.J. Shulman. and N. Hozumi.1984. Transposition of two different intracisternal A particle elements into an immunoglobulin kappa-chain gene. Mol Cell Biol.4:2565-2572.
16. Irani, Y., M. Tea. R.G. Tilton. D.J. Coster. K.A. Williams. and H.M. Brereton. 2008. PCR amplification of the functional immunoglobulin heavy chain variable gene from a hybridoma in the presence of two aberrant transcripts. J Immunol Methods.336:246-250.
17. Kabat, E.A., T.T. Wu. H.M.G.K.S. Perry. and C. Foeller.1991. Sequences of Proteins of Immunological Interest,5th ed. US Department of Health and Human Services, National Institutes of Health.
18. Kelley, D.E., C. Coleclough.and R.P. Perry.1982. Functional significance and evolutionary development of the 5'-terminal regions of immunoglobulin variable-region genes. Cell.29:681-689.
19. Krebber, A., S. Bornhauser. J. Burmester. A. Honegger. J. Willuda. H.R. Bosshard. and A. Pluckthun.1997. Reliable cloning of functional antibody variable domains from hybridomas and spleen cell repertoires employing a reengineered phage display system. J. Immunol. Methods.201:35-55.
20. Kwan, S.P., E.E. Max. J.G. Seidman. P. Leder. and M.D. Scharff.1981.Two kappa immunoglobulin genes are expressed in the myeloma S107. Cell.26: 57-66.
21. Lei. P., Y. He. Q. Ye. H.F. Zhu. X.M. Yuan. J. Liu. W. Xing. S. Wu. W. Dai. X. Shen. G.B. Wang. G.X. Shen.2007. Antigen-binding characteristics of AbCD71 and its inhibitory effect on PHA-induced lymphoproliferation. Acta Pharmacol Sin.28:1659-1664.
22. Liesegang, B., A. Radbruch. and K. Rajewsky.1978. Isolation of myeloma variants with predefined variant surface immunoglobulin by cell sorting. Proc Natl Acad Sci U S A.75:3901-3905.
23. Liu, J., D. Xiao. X. Zhou. X. Wen. H. Dai. Z. Wang. X. Shen. W. Dai. D. Yang. and G. Shen.2008. Preparation and identification of scFv and bsFv against transferrin receptor.J Huazhong Univ Sci Technolog Med Sci.28:621-625.
24. Lossos, I.S., R. Tibshirani. B. Narasimhan. and R. Levy.2000. The inference of antigen selection on Ig genes. J. Immunol.165:5122-5126.
25. Lutz, J., W. Muller. and H.M. Jack.2006.VH Replacement Rescues Progenitor B Cells with Two Nonproductive VDJ Alleles.J Immunol.177:7007-7014.
26. Joho, R., I.L. Weissman. P. Early. J. Cole. and L. Hood.1980. Organization of Kappa light chain genes in germ-line and somatic tissue. Proc Natl Acad Sci U S A.77:1106-1110.
27. Juste, M., J. Muzard. and P. Billiald.2006. Cloning of the antibody light chain V-gene from murine hybridomas by bypassing the aberrant MOPC21-derived transcript.Anal Biochem.349:159-161.
28. Navazza, V., S. Gabba. A. Alfieri. S. Giorgetti. L. Marchese. G. Palladini. A. Mattevi. E. Ascari. R. Caporali. C. Montecucco. M. G. erlini. and V. Perfetti. 2008. Characterization of immunoglobulin variable regions of two human pathogenic monoclonal cryocrystalglobulins. Mol. Immunol.45:1519-1524.
29. Ni, M., B. Yu. Y. Huang. Z. Tang. P. Lei. X. Shen. W. Xin. H. Zhu. G. Shen. 2008. Homology modelling and bivalent single-chain Fv construction of anti-HL-60 single-chain immunoglobulin Fv fragments from a phage display library. J Biosci.33:691-697.
30. Nishi, M., T. KataoKa. T. Honjo. T. KataoKa. and T. Honjo.1985. Preferential rearrangement of the immunoglobulin Kappa chain joining region J Kappa 1 and J Kappa 2 segments in mouse spleen DNA. Proc Natl Acad Sci U S A.82: 6399-6403.
31. Peng, J.L., S. Wu. X.P, Zhao, M. Wang. W.H. Li. X. Shen. J. Liu. P. Lei. H.F. Zhu. and G.X. Shen.2007. Downregulation of transferrin receptor surface expression by intracellular antibody.Biochem Biophys Res Commun.354: 864-871.
32. Qing Y, W. Shuo. W. Zhihua. Z. Huifen. L. Ping. L. Lijiang. Z. Xiaorong. C. Liming. X. Daiwen. H. Yu. X. Wei. M. Fin. F. Zuohua. and S. Guanxin. 2006.The in vitro antitumor effect and in vivo tumor-specificity distribution of human-mouse chimeric antibody against transferrin receptor.Cancer Immunol Immunother.55:1111-21
33. Rose, S.M., W.M. Kuehl. and G.P. Smith.1977. Cloned MPC 11 myeloma cells express two Kappa genes:a gene for a complete light chain and a gene for a constant region polypeptide. Cell.12:2453-2462.
34. Shen X, H.F. Zhu. F.R. He. W. Xing. L. Li. J. Liu. J. Yang. X.F. Pan. P. Lei. Z.H. Wang. G.X. Shen.2008, An anti-transferrin receptor antibody enhanced the growth inhibitory effects of chemotherapeutic drugs on human non-hematopoietic tumor cells. Int Immunopharmacol.8:1813-1820.
35. Shen, X., G.B. Hu. J. S. Jiang. F.R. He. W. Xing. L. Li. J. Yang. H.F. Zhu. P. Lei. G.X Shen.2009. Engineering and characterization of a baculovirus expressed mouse/human chimeric antibody against transferrin receptor. Protein Eng Des Sel.22:723-731.
36. Shlomchik, M.J., A.H. Aucoin. D.S. Pisetsky. and M.G. Weigert.1987. Structure and function of anti-DNA autoantibodies derived from a single autoimmune mouse. Proc Natl Acad Sci U S A.84:9150-9154.
37. Smith, G.P.,1978. Sequence of the full-length immunoglobulin kappa-chain of mouse myeloma MPC11.Biochem J.171:337-347.
38. Souto-Carneiro, M.M., G.P. Sims. H. Girschik. J. Lee. and P.E. Lipsky.2005. Developmental Changes in the Human Heavy Chain CDR3. J. Immunol.175: 7425-7436.
39. Schwede. T., J. Kopp. N. Guex. and M.C. Peitsch.2003.SWISS-MODEL:an automated protein homology-modeling server. Nucleic Acids Research.31: 3381-3385.
40. Vela, J.L., D. Ait-Azzouzene. B.H. Duong. T. Ota.and D. Nemazee.2008. Rearrangement of mouse immunoglobulin Kappa deleting element recombining sequence promotes immune tolerance and lambda B cell production. Immunity. 28:161-170.
41. Wang, S., G.X. Shen.L. Jiang. X.L. Wang. W. Xiong. and C.X. Lu.1999. Sequence analysis of functional and nonfunctional VK genes from a hybridoma. Chinese Journal of Immunology 15:82-84.
42. Wilson, P.C., O. de. Bouteiller. Y.J. Liu. K. Potter. Banchereau. J.D. Capra. and V. Pascual.1998. Somatic Hypermutation introduces insertions and deletions into immunoglobulin V genes. J. Exp. Med.5:59-70.
43. Xu, D.,2006. Dual surface immunoglobulin light-chain expression in B-cell lymphoproliferative disorders. Arch Pathol Lab Med.130:853-856.
44. Yuan, X., M.J. Gubbins. and J.D.Berry.2004. A simple and rapid protocol for the sequence determination of functional kappa light chain cDNAs from aberrant-chain-positive murine hybridomas.J Immunol Methods.294:199-207.
45. Zack, D.J., A.L. Wong. S. M. tempniak. and R.H. Weisbart.1995. Two kappa immunoglobulin light chains are secreted by an anti-DNA hybridoma: implications for isotypic exclusion. Mol Immunol.32:1345-53.
1. Dujic J, Kippenberger S, Ramirez-Bosca A,Diaz-Alperi J, Bereiter-Hahn J, Kaufmann R, Bemd A, Hofmann M.,2009.Curcumin in combination with visible light inhibits tumor growth in a xenograft tumor model. Int J Cancer.6, 1422-1428.
2. Dandekar PP, Jain R, Patil S, Dhumal R, Tiwari D, Sharma S, Vanage G, Patravale V.,2010. Curcumin-loaded hydrogel nanoparticles:application in anti-malarial therapy and toxicological evaluation. J Pharm Sci.12,4992-5010.
3. Tang H, Murphy CJ, Zhang B, Shen Y, Sui M, Van Kirk EA, Feng X, Murdoch WJ., 2010.Amphiphilic curcumin conjugate-forming nanoparticles as anticancer prodrug and drug carriers:in vitro and in vivo effects.Nanomedicine (Lond).6, 855-865.
4. Duan J, Zhang Y, Han S, Chen Y, Li B, Liao M, Chen W, Deng X, Zhao J, Huang B.,2010. Synthesis and in vitro/in vivo anti-cancer evaluation of curcumin-loaded chitosan/poly (butyl cyanoacrylate) nanoparticles. Int J Pharm.1-2,211-220.
5. Anand P, Nair HB, Sung B, Kunnumakkara AB, Yadav VR, Tekmal RR, Aggarwal BB.,2010. Design of curcumin-loaded PLGA nanoparticles formulation with enhanced cellular uptake, and increased bioactivity in vitro and superior bioavailability in vivo. Biochem Pharmacol.3,330-338.
6. Yallapu MM, Maher DM, Sundram V, Bell MC, Jaggi M, Chauhan SC.,2010. Curcumin induces chemo/radio-sensitization in ovarian cancer cells and curcumin nanoparticles inhibit ovarian cancer cell growth. J Ovarian Res.29,11.
7. Xinna Wang, Xinshu Xia, Chuanshan Xu, Jing Xu, Ping Wang, Junyan Xiang, Dingqun Bai, Wingnang Leung A.2011. Ultrasound-induced cell death of nasopharyngeal carcinoma cells in the presence of curcumin. Integr Cancer Ther. 1,70-76.
8. Yau, K.Y., Dubuc, G., Li, S., Hirama, T., Mackenzie, C.R., Jermutus, L., Hall, J.C., Tanha, J.,2005.Affinity maturation of a VHH by mutational hotspot randomization. J. Immunol. Methods.297,213-224
9. Onoue S, Takahashi H, Kawabata Y, Seto Y, Hatanaka J, Timmermann B, Yamada S.,2010. Formulation design and photochemical studies on nanocrystal solid dispersion of curcumin with improved oral bioavailability. J Pharm Sci.4, 1871-1881.
10. Hegge AB, Andersen T, Melvik JE, Kristensen S, Tonnesen HH.,2010. Evaluation of novel alginate foams as drug delivery systems in antimicrobial photodynamic therapy (aPDT) of infected wounds--an in vitro study:studies on curcumin and curcuminoides XL. J Pharm Sci.8,3499-3513.
11. Hegge AB, Andersen T, Melvik JE, Bruzell E, Kristensen S, Tonnesen HH.,2011. Formulation and bacterial phototoxicity of curcumin loaded alginate foams for wound treatment applications:studies on curcumin and curcuminoides XLII. J Pharm Sci.1,174-185.
12. Manju S, Sreenivasan K.,2011. Synthesis and characterization of a cytotoxic cationic polyvinylpyrrolidone-curcumin conjugate. J Pharm Sci.2,504-511.
13. Huang Q, Yu H, Ru Q.,2010. Bioavailability and delivery of nutraceuticals using nanotechnology. J Food Sci.1,50-57.
14. Yen FL, Wu TH, Tzeng CW, Lin LT, Lin CC.,2010. Curcumin nanoparticles improve the physicochemical properties of curcumin and effectively enhance its antioxidant and antihepatoma activities. J Agric Food Chem.12,7376-7382.
15. Simoni E, Bergamini C, Fato R, Tarozzi A, Bains S, Motterlini R, Cavalli A, Bolognesi ML, Minarini A, Hrelia P, Lenaz G, Rosini M, Melchiorre C.,2010. Polyamine conjugation of curcumin analogues toward the discovery of mitochondria-directed neuroprotective agents. Med Chem.19,7264-7268.
16. Nair HB, Sung B, Yadav VR, Kannappan R, Chaturvedi MM, Aggarwal BB., 2010.Delivery of antiinflammatory nutraceuticals by nanoparticles for the prevention and treatment of cancer. Biochem Pharmacol.12,1833-1843.
17. Shehzad A, Wahid F, Lee YS.,2010. Curcumin in cancer chemoprevention: molecular targets, pharmacokinetics, bioavailability, and clinical trials.Arch Pharm (Weinheim).343,489-499.
18. Talavera A, Eriksson A, Okvist M, Lopez-Requena A, Fernandez-Marrero Y, Perez R, Moreno E, Krengel U,2009. Crystal structure of an anti-ganglioside antibody, and modelling of the functional mimicry of its NeuGc-GM3 antigen by an anti-idiotypic antibody. Mol Immunol.46,3466-3475.
19. Lin L, Deangelis S, Foust E, Fuchs J, Li C, Li PK, Schwartz EB, Lesinski GB, Benson D, Lu J, Hoyt D, Lin J.,2010. A novel small molecule inhibits STAT3 phosphorylation and DNA binding activity and exhibits potent growth suppressive activity in human cancer cells. Mol Cancer.16; 217.
20. Hegge AB, Andersen T, Melvik JE, Kristensen S, T(?)nnesen HH.,2010. Evaluation of novel alginate foams as drug delivery systems in antimicrobial photodynamic therapy (aPDT)of infected wounds--an in vitro study:studies on curcumin and curcuminoides XL. J Pharm Sci.8,3499-3513.
21. Hegge AB, Andersen T, Melvik JE, Bruzell E, Kristensen S, T(?)nnesen HH.,2011. Formulation and bacterial phototoxicity of curcumin loaded alginate foams for wound treatment applications:studies on curcumin and curcuminoides XLII. J Pharm Sci. Jan.1,174-185.
22. Dandekar PP, Jain R, Patil S, Dhumal R, Tiwari D, Sharma S, Vanage G, Patravale V.,2010. Dec; Curcumin-loaded hydrogel nanoparticles:application in anti-malarial therapy and toxicological evaluation. Pharm Sci.12,4992-5010.
23. Manju S, Sreenivasan K.,2011. Synthesis and characterization of a cytotoxic cationic polyvinylpyrrolidone-curcumin conjugate. J Pharm Sci.2,504-511.
24. Xinna Wang, Xinshu Xia, Chuanshan Xu, Jing Xu, Ping Wang, Junyan Xiang, Dingqun Bai, Wingnang Leung A.,2011. Ultrasound-induced cell death of nasopharyngeal carcinoma cells in the presence of curcumin. Integr Cancer Ther. 1,70-76.
25. Wang F, Huang W, Zhang Y, Wang M, Sun L, Tang B, Wang W.,2011. Determination of protein by fluorescence enhancement of curcumin in lanthanum-curcumin-sodium dodecyl benzene sulfonate-protein system. J Fluoresc.1,25-34.
26. Heng MC.2010. Curcumin targeted signaling pathways:basis for anti-photoaging and anti-carcinogenic therapy. Int J Dermatol.6,608-622.
27. Rowe DL, Ozbay T, O'Regan RM, Nahta R.,2009. Modulation of the BRCA1 protein and induction of apoptosis in triple negative breast cancer cell lines by the polyphenolic compound curcumin. Breast Cancer.3,61-75.
28. Yen FL, Wu TH, Tzeng CW, Lin LT, Lin CC.,2010.Curcumin nanoparticles improve the physicochemical properties of curcumin and effectively enhance its antioxidant and antihepatoma activities. J Agric Food Chem.58,7376-82.
29. Zheng Z, Zhang X, Carbo D, Clark C, Nathan C, Lvov Y.,2010. Sonication-assisted synthesis of polyelectrolyte-coated curcumin nanoparticles. Langmuir.11,7679-7681.
30. Agrawal DK, Mishra PK.,2010.Curcumin and its analogues:potential anticancer agents. Med Res Rev.30,818-860.
31. Chwilkowska A, Kulbacka J, Saczko J.,2011. Death of tumor cells. Photodynamic reaction in apoptosis induction in cancer cells. Pol Merkur Lekarski.30,45-48.
32. Ran C, Zhang Z, Hooker J, Moore A.,2011. In Vivo Photoactivation Without "Light":Use of Cherenkov Radiation to Overcome the Penetration Limit of Light. Mol Imaging Biol. May 3.
33. Ritter CG, Kuhl IC, Lenhardt C, Weissbluth ML, Bakos RM.2010. Photodynamic therapy with delta-aminolevulinic acid and light-emitting diodes in actinic keratosis.An Bras Dermatol.5,639-645.
34. Bhowmick R, Girotti AW.,2011. Rapid upregulation of cytoprotective nitric oxide in breast tumor cells subjected to a photodynamic therapy-like oxidative challenge.Photochem Photobiol.87,78-86.
35.许川山, Albert Wing, NangLeung,中药姜黄素的光谱学特性研究,激光杂志,2005年第26卷第4期。
36.许川山,Albert Wing, NangLeung,中药光敏剂介导的光动力疗,激光杂志,2004年第25卷第6期。
37.吕庆銮,张苗,岳宁宁,宫斌,王怀友,荧光探针法研究铜离子102姜黄素体系中021-的反应机理及在02存在下02的测定,高等学校化学学报,2009年第三期。
38.孙晶,季宇彬,新型姜黄素脂质体的制备和初步稳定性考察,2008年第十卷第四期。
39.刘仲荣,杨慧兰,皮肤病光动力疗法系列讲座(二)光敏剂的研究进展,中国美容医学,2009年4月18卷4期。
40.张苗,吕庆銮,岳宁宁,王怀友,酶催化-荧光猝灭法测定药物中的姜黄素,化学分析计量,2008年第17卷第6期。
41.施文荣,刘艳,姜黄素诱导人胃腺癌BGC-823细胞凋亡的光动力学研究,中华中医药学刊,2009年第27卷第9期。
42.吴晓健,吴凯南,董蒲江,姜黄素诱导人乳腺癌MCF27细胞凋亡的研究,重庆医学,2005年12月第34卷第12期。
43.回学军,孙冬,于庭,李树岩,吴东辉,姜黄素诱导K562细胞凋亡及其对细胞周期各时相影响,中国实验诊断学,2008年7月第12卷第7期。
44.霍红梅,张利元,江家贵,朱旬,姜黄素抑制乳腺癌MCF27细胞增殖及其相关的氧化应激机制,中国肿瘤生物治疗杂志,2009年十月第16卷第五期5。
45.宋洪杰,张玉梅,高丽红,姜黄素无水乙醇溶液的光稳定性研究,中国药学杂志,2009年3月第44卷第6期。
46.孙黎,刘正泉,罗强,薄爱华,姜黄素体外诱导人乳腺癌MCF27细胞凋亡作用,河北北方医学学院学报；2009年8月第26卷第四期。
47.张庆云,莫曾南,姜黄素生物利用度研究进展,China Pharmacy,2009 Vol.20 No.33。
48.李石伟,刘跃明,姜黄素联合热疗对Hep22细胞凋亡及细胞周期的影响,ChinJ Lab Diagn,November,2009,Vol 13, No.11。
49.王双玲,陈元玉,何顺华,刘峰,李冠武,姜黄素抗急性白血病机制研究,汕头大学医学院学报,2008年。
50. Kunnumakkara AB, Anand P, Aggarwal BB.,2008. Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett.269,99-225.
51. Anand P, Nair HB, Sung B, Kunnumakkara AB, Yadav VR, Tekmal RR, Aggarwal BB.,2010. Design of curcumin-loaded PLGA nanoparticles formulation with enhanced cellular uptake, and increased bioactivity in vitro and superior bioavailability in vivo.Biochem Pharmacol.79,30-38.
2.厉红元,车艺,汤为学,姜黄素对人肝癌细胞增殖和凋亡的影响,中华肝脏病杂志,2002年06期。
3.薛妍,夏天,赵建斌,吴少华,张仲海,王宗仁,姜黄素对人肝癌细胞SMMC-7721的抑制作用,第四军医大学学报2000年第21卷第5期。
4.王牡,阮余霞,彭元,陈伟,蔡继业,姜黄素对人肝癌HepG2细胞毒性的分析。
5.王伟章,张碧鱼,陈宏远,张黎,姜黄素对人肝癌细胞Sk-Hep-1抗癌作用的研究[J].中国中药杂志,2010,35(4)：485.
6.郑丽端,童强松,吴翠环,曾甫清,姜黄素诱导卵巢癌细胞系A2780细胞周期阻滞和凋亡,华中科技大学学报(医学版)
7.施文荣,张振林,刘艳,光照对姜黄素诱导人乳腺癌MCF-7细胞凋亡的影响,广东医学院学报,2009年第27卷第二期。
8.蒋福升,徐秀玲,金波,陈铌铍,高承贤,丁志山,吕圭源,水溶性姜黄素前药制备及其体外抗肿瘤实验研究,中国药学杂志,2009年10月第44卷第19期。
9.曾霞波,夏新蜀,余和平,白定群,谭勇,何勇,许川山,光敏化姜黄素对人乳腺癌细胞的抑制作用,激光杂志,2008年第29卷第2期。
10.陈瑞川,苏金华,马胜平,蒋雪玄,霍霞,光敏化姜黄素诱导胃癌细胞凋亡,癌症,2000年第19卷第4期。
11.王伟章,张碧鱼,袁健,毛建文,梅文杰,姜黄素对肝癌细胞JAK-STAT信号通路的影响,药学学报,2009,44,1434-1439。
12.曹军,姜丽平,耿成燕,姚晓峰,仲来福,活性氧在姜黄素对人胚肾293细胞细胞毒性中的作用,毒理学杂志,2009年8月第23卷第4期。
13. Zhang Z, Cao W, Jin H, Lovell JF, Yang M, Ding L, Chen J, Corbin I, Luo Q, Zheng G, Biomimetic nanocarrier for direct cytosolic drug delivery.Angew Chem Int Ed Engl.2009; 48,9171-5.
14. Zhang Z, Chen J, Ding L, Jin H, Lovell JF, Corbin IR, Cao W, Lo PC, Yang M, Tsao MS, Luo Q, Zheng G, HDL-mimicking peptide-lipid nanoparticles with improved tumor targeting. Small.2010,6,430-7.
15. Jiao Y, Wilkinson J 4th, Di X, Wang W, Hatcher H, Kock ND D'Agostino R Jr, Knovich MA, Torti FM, Torti SV. Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator. Blood.2009,113, 462-9.
16. Gururajan M, Dasu T, Shahidain S, Jennings CD, Robertson DA, Rangnekar VM, Bondada S, Spleen tyrosine kinase (Syk), a novel target of curcumin, is required for B lymphoma growth.J Immunol.2007,178,111-21.
17. Egan ME, Pearson M, Weiner SA, Rajendran V, Rubin D, Glockner-Pagel J, Canny S, Du K, Lukacs GL, Caplan MJ., Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects.Science.2004,304,600-2.
18. Zhang M, Murakami T, Ajima K, Tsuchida K, Sandanayaka AS, Ito O, Iijima S, Yudasaka M., Fabrication of ZnPc/protein nanohorns for double photodynamic and hyperthermic cancer phototherapy. Proc Natl Acad Sci U S A.2008,105, 14773-8.
19. Weitman SD, Weinberg AG, Coney LR, Zurawski VR, Jennings DS, Kamen BA., Cellular localization of the folate receptor:potential role in drug toxicity and folate homeostasis. Cancer Res.1992,52,6708-11.
20. Weitman SD, Weinberg AG, Coney LR, Zurawski VR, Jennings DS, Kamen BA., Cellular localization of the folate receptor:potential role in drug toxicity and folate homeostasis. Cancer Res.1992,52,6708-11.
21.陈昆,李文新,激光纳米治疗癌症研究发现新途径,中国激光,2005,32,12,1698.
22. O'Neal DP, Hirsch LR, Halas NJ, Payne JD, West JL, Photo-thermal tumor ablation in mice using near infrared-absorbing nanoparticles. Cancer Lett.2004, 209,171-6.
23. Overgaard J., The current and potential role of hyperthermia in radiotherapy.Int J Radiat Oncol Biol Phys.1989 16,535-49.
24.邱海霞,刘凡光,顾瑛,肿瘤光动力学疗法免疫机制的研究进展,中国激光医学杂志,2005,14,105-113.
25. Korbelik M, Dougherty GJ., Photodynamic therapy-mediated immune response against subcutaneous mouse tumors.Cancer Res.1999,59,1941-6.
26. Zhang H, Ma W, Li Y., Generation of effective vaccines against liver cancer by using photodynamic therapy.Lasers Med Sci.2009,24,549-52
27. Preise D, Oren R, Glinert I, Kalchenko V, Jung S, Scherz A, Salomon Y. Systemic antitumor protection by vascular-targeted photodynamic therapy involves cellular and humoral immunity. Cancer Immunol Immunother.2009,58, 71-84.
28. Korbelik M, Sun J., Photodynamic therapy-generated vaccine for cancer therapy. Cancer Immunol Immunother.2006,55,900-9.
29. Vonarx V, Foultier MT, Anasagasti L, Morlet L, Lajat Y, Patrice T. Photodynamic effect on the specific antitumor immune activity. Int J Immunopharmacol.1997,19,101-10.
30. Krosl G, Korbelik M, Krosl J, Dougherty GJ., Potentiation of photodynamic therapy-elicited antitumor response by localized treatment with granulocyte-macrophage colony-stimulating factor.Cancer Res.1996,56,3281-6.
31. Sanoj Rejinold N, Sreerekha PR, Chennazhi KP, Nair SV, Jayakumar R., Biocompatible, biodegradable and thermo-sensitive chitosan-g-poly (N-isopropylacrylamide) nanocarrier for curcumin drug delivery.Int J Biol Macromol.2011, Apr 22.
32. Sasaki H, Sunagawa Y, Takahashi K, Imaizumi A, Fukuda H, Hashimoto T, Wada H, Katanasaka Y, Kakeya H, Fujita M, Hasegawa K, Morimoto T., Innovative preparation of curcumin for improved oral bioavailability.Biol Pharm Bull.2011, 34,660-5.
33. Reuter S, Gupta SC, Park B, Goel A, Aggarwal BB., Epigenetic changes induced by curcumin and other natural compounds.Genes Nutr.2011, Apr 24.
34. Katsori AM, Chatzopoulou M, Dimas K, Kontogiorgis C, Patsilinakos A, Trangas T, Hadjipavlou-Litina D., Curcumin analogues as possible anti-proliferative & anti-inflammatory agents. Eur J Med Chem.2011, Apr 5.
35. Qian H, Yang Y, Wang X., Curcumin enhanced adriamycin-induced human liver-derived Hepatoma G2 cell death through activation of mitochondria-mediated apoptosis and autophagy. Eur J Pharm Sci.2011, Apr 14
36. Zhang H, Zhang L, Yuan P, Wang C., Preparation and in vitro release characteristics of curcumin in nanosuspensions. Zhongguo Zhong Yao Za Zhi. 2011,36,132-5.
37. Darvesh AS, Aggarwal BB, Bishayee A., Curcumin and Liver Cancer:A Review.Curr Pharm Biotechnol.2011, Apr 5.
38. Lee YJ, Kim NY, Suh YA, Lee C., Involvement of ROS in Curcumin-induced Autophagic Cell Death. Korean J Physiol Pharmacol.2011,15,1-7.
39. Hegde ML, Hegde PM, Rao KS, Mitra S., Oxidative genome damage and its repair in neurodegenerative diseases:function of transition metals as a double-edged sword.J Alzheimers Dis.2011,4,183-98.
40. Sanphui P, Goud NR, Khandavilli UB, Bhanoth S, Nangia A., New polymorphs of curcumin. Chem Commun (Camb).2011,47,5013-5.
41. Griesser M, Pistis V, Suzuki T, Tejera N, Pratt DA, Schneider C., Autoxidative and cyclooxygenase-2 catalyzed transformation of the dietary chemopreventive agent curcumin. J Biol Chem.2011,286,1114-24.
1. Arnold, K., L. Bordoli. J Kopp. and T. Schwede.2006. The SWISS-MODEL Workspace:A web-based environment for protein structure homology modelling. Bioinformatics.22:195-201.
2. Barderas, R., J. Desmet. P. Timmerman. R. Meloen. and J.I.Casal.2008. Affinity maturation of antibodies assisted by in silico modeling. Proc Natl Acad Sci U S A.105:9029-9034.
3. Blatt, N.B., R.M. Bill. and G.D. Glick.1998. Characterization of a unique anti-DNA hybridoma. Hybridoma 17:33-39.
4. Benkert, P., M. Biasini. and T.Schwede.2011. Toward the estimation of the absolute quality of individual protein structure models. Bioinformatics, 27:343-350.
5. Bose, B., and S. Sinha.2005. Problems in using statistical analysis of replacement and silent mutations in antibody genes for determining antigen-driven affinity selection. Immunology 116:172-183
6. Brochet, X., M.P.Lefranc. and V. Giudicelli.2008. IMGT/V-QUEST:the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysis. Nucl. Acids Res.36:503-508.
7. Carey, J.B., C.S. Moffatt-Blue. L.C. Watson. A.L. Gavin. and A.J. Feeney. 2008. Repertoire-based selection into the marginal zone compartment during B cell development. J. Exp. Med.205:2043-2052.
8. Carroll,W.L., E.Mendel. and S. Levy.1988. Hybridoma fusion cell lines contain an aberrant kappa transcript. Mol. Immunol.25:991.
9. Chang, B. and P. Casali.1994. The CDR1 sequences of a major proportion of human germline Ig VH genes are inherently susceptible to amino acid replacement. Immunol Today.15:367-373.
10. Chemin. G., A. Tinguely. C. Sirac. F. Lechouane. S. Duchez. M. Cogne. and L.Delpy.2010. Multiple RNA surveillance mechanisms cooperate to reduce the amount of nonfunctional Ig kappa transcripts. J Immunol.184:5009-5017.
11. Chen, C., V.A. Roberts.and M. B. Rittenberg.1992. Generation and analusis of random point mutations in an antibody CDR2 sequence:many mutated antibodies lose their ability to bind antigen. J.Exp.Med.176:855-866.
12. Chen, D., K. Altmann. P.J. Hanna. A. Tammer.and J.R. Underwood. 1997.Detection of two isotypically different antibodies produced by a murine hybridoma. Hybridoma 16:195-199.
13. Diaw, L., D. Siwarski. W. DuBois. G. Jones. and K. Huppi.2000. Double producers of kappa and lambda define a subset of B cells in mouse plasmacytomas. Mol Immunol.37:775-781.
14. Guex, N. and M. C. Peitsch.1997. SWISS-MODEL and the Swiss-PdbViewer: An environment for comparative protein modelling. Electrophoresis.18: 2714-2723.
15. Hawley, R.G., M.J. Shulman. and N. Hozumi.1984. Transposition of two different intracisternal A particle elements into an immunoglobulin kappa-chain gene. Mol Cell Biol.4:2565-2572.
16. Irani, Y., M. Tea. R.G. Tilton. D.J. Coster. K.A. Williams. and H.M. Brereton. 2008. PCR amplification of the functional immunoglobulin heavy chain variable gene from a hybridoma in the presence of two aberrant transcripts. J Immunol Methods.336:246-250.
17. Kabat, E.A., T.T. Wu. H.M.G.K.S. Perry. and C. Foeller.1991. Sequences of Proteins of Immunological Interest,5th ed. US Department of Health and Human Services, National Institutes of Health.
18. Kelley, D.E., C. Coleclough.and R.P. Perry.1982. Functional significance and evolutionary development of the 5'-terminal regions of immunoglobulin variable-region genes. Cell.29:681-689.
19. Krebber, A., S. Bornhauser. J. Burmester. A. Honegger. J. Willuda. H.R. Bosshard. and A. Pluckthun.1997. Reliable cloning of functional antibody variable domains from hybridomas and spleen cell repertoires employing a reengineered phage display system. J. Immunol. Methods.201:35-55.
20. Kwan, S.P., E.E. Max. J.G. Seidman. P. Leder. and M.D. Scharff.1981.Two kappa immunoglobulin genes are expressed in the myeloma S107. Cell.26: 57-66.
21. Lei. P., Y. He. Q. Ye. H.F. Zhu. X.M. Yuan. J. Liu. W. Xing. S. Wu. W. Dai. X. Shen. G.B. Wang. G.X. Shen.2007. Antigen-binding characteristics of AbCD71 and its inhibitory effect on PHA-induced lymphoproliferation. Acta Pharmacol Sin.28:1659-1664.
22. Liesegang, B., A. Radbruch. and K. Rajewsky.1978. Isolation of myeloma variants with predefined variant surface immunoglobulin by cell sorting. Proc Natl Acad Sci U S A.75:3901-3905.
23. Liu, J., D. Xiao. X. Zhou. X. Wen. H. Dai. Z. Wang. X. Shen. W. Dai. D. Yang. and G. Shen.2008. Preparation and identification of scFv and bsFv against transferrin receptor.J Huazhong Univ Sci Technolog Med Sci.28:621-625.
24. Lossos, I.S., R. Tibshirani. B. Narasimhan. and R. Levy.2000. The inference of antigen selection on Ig genes. J. Immunol.165:5122-5126.
25. Lutz, J., W. Muller. and H.M. Jack.2006.VH Replacement Rescues Progenitor B Cells with Two Nonproductive VDJ Alleles.J Immunol.177:7007-7014.
26. Joho, R., I.L. Weissman. P. Early. J. Cole. and L. Hood.1980. Organization of Kappa light chain genes in germ-line and somatic tissue. Proc Natl Acad Sci U S A.77:1106-1110.
27. Juste, M., J. Muzard. and P. Billiald.2006. Cloning of the antibody light chain V-gene from murine hybridomas by bypassing the aberrant MOPC21-derived transcript.Anal Biochem.349:159-161.
28. Navazza, V., S. Gabba. A. Alfieri. S. Giorgetti. L. Marchese. G. Palladini. A. Mattevi. E. Ascari. R. Caporali. C. Montecucco. M. G. erlini. and V. Perfetti. 2008. Characterization of immunoglobulin variable regions of two human pathogenic monoclonal cryocrystalglobulins. Mol. Immunol.45:1519-1524.
29. Ni, M., B. Yu. Y. Huang. Z. Tang. P. Lei. X. Shen. W. Xin. H. Zhu. G. Shen. 2008. Homology modelling and bivalent single-chain Fv construction of anti-HL-60 single-chain immunoglobulin Fv fragments from a phage display library. J Biosci.33:691-697.
30. Nishi, M., T. KataoKa. T. Honjo. T. KataoKa. and T. Honjo.1985. Preferential rearrangement of the immunoglobulin Kappa chain joining region J Kappa 1 and J Kappa 2 segments in mouse spleen DNA. Proc Natl Acad Sci U S A.82: 6399-6403.
31. Peng, J.L., S. Wu. X.P, Zhao, M. Wang. W.H. Li. X. Shen. J. Liu. P. Lei. H.F. Zhu. and G.X. Shen.2007. Downregulation of transferrin receptor surface expression by intracellular antibody.Biochem Biophys Res Commun.354: 864-871.
32. Qing Y, W. Shuo. W. Zhihua. Z. Huifen. L. Ping. L. Lijiang. Z. Xiaorong. C. Liming. X. Daiwen. H. Yu. X. Wei. M. Fin. F. Zuohua. and S. Guanxin. 2006.The in vitro antitumor effect and in vivo tumor-specificity distribution of human-mouse chimeric antibody against transferrin receptor.Cancer Immunol Immunother.55:1111-21
33. Rose, S.M., W.M. Kuehl. and G.P. Smith.1977. Cloned MPC 11 myeloma cells express two Kappa genes:a gene for a complete light chain and a gene for a constant region polypeptide. Cell.12:2453-2462.
34. Shen X, H.F. Zhu. F.R. He. W. Xing. L. Li. J. Liu. J. Yang. X.F. Pan. P. Lei. Z.H. Wang. G.X. Shen.2008, An anti-transferrin receptor antibody enhanced the growth inhibitory effects of chemotherapeutic drugs on human non-hematopoietic tumor cells. Int Immunopharmacol.8:1813-1820.
35. Shen, X., G.B. Hu. J. S. Jiang. F.R. He. W. Xing. L. Li. J. Yang. H.F. Zhu. P. Lei. G.X Shen.2009. Engineering and characterization of a baculovirus expressed mouse/human chimeric antibody against transferrin receptor. Protein Eng Des Sel.22:723-731.
36. Shlomchik, M.J., A.H. Aucoin. D.S. Pisetsky. and M.G. Weigert.1987. Structure and function of anti-DNA autoantibodies derived from a single autoimmune mouse. Proc Natl Acad Sci U S A.84:9150-9154.
37. Smith, G.P.,1978. Sequence of the full-length immunoglobulin kappa-chain of mouse myeloma MPC11.Biochem J.171:337-347.
38. Souto-Carneiro, M.M., G.P. Sims. H. Girschik. J. Lee. and P.E. Lipsky.2005. Developmental Changes in the Human Heavy Chain CDR3. J. Immunol.175: 7425-7436.
39. Schwede. T., J. Kopp. N. Guex. and M.C. Peitsch.2003.SWISS-MODEL:an automated protein homology-modeling server. Nucleic Acids Research.31: 3381-3385.
40. Vela, J.L., D. Ait-Azzouzene. B.H. Duong. T. Ota.and D. Nemazee.2008. Rearrangement of mouse immunoglobulin Kappa deleting element recombining sequence promotes immune tolerance and lambda B cell production. Immunity. 28:161-170.
41. Wang, S., G.X. Shen.L. Jiang. X.L. Wang. W. Xiong. and C.X. Lu.1999. Sequence analysis of functional and nonfunctional VK genes from a hybridoma. Chinese Journal of Immunology 15:82-84.
42. Wilson, P.C., O. de. Bouteiller. Y.J. Liu. K. Potter. Banchereau. J.D. Capra. and V. Pascual.1998. Somatic Hypermutation introduces insertions and deletions into immunoglobulin V genes. J. Exp. Med.5:59-70.
43. Xu, D.,2006. Dual surface immunoglobulin light-chain expression in B-cell lymphoproliferative disorders. Arch Pathol Lab Med.130:853-856.
44. Yuan, X., M.J. Gubbins. and J.D.Berry.2004. A simple and rapid protocol for the sequence determination of functional kappa light chain cDNAs from aberrant-chain-positive murine hybridomas.J Immunol Methods.294:199-207.
45. Zack, D.J., A.L. Wong. S. M. tempniak. and R.H. Weisbart.1995. Two kappa immunoglobulin light chains are secreted by an anti-DNA hybridoma: implications for isotypic exclusion. Mol Immunol.32:1345-53.
1. Dujic J, Kippenberger S, Ramirez-Bosca A,Diaz-Alperi J, Bereiter-Hahn J, Kaufmann R, Bemd A, Hofmann M.,2009.Curcumin in combination with visible light inhibits tumor growth in a xenograft tumor model. Int J Cancer.6, 1422-1428.
2. Dandekar PP, Jain R, Patil S, Dhumal R, Tiwari D, Sharma S, Vanage G, Patravale V.,2010. Curcumin-loaded hydrogel nanoparticles:application in anti-malarial therapy and toxicological evaluation. J Pharm Sci.12,4992-5010.
3. Tang H, Murphy CJ, Zhang B, Shen Y, Sui M, Van Kirk EA, Feng X, Murdoch WJ., 2010.Amphiphilic curcumin conjugate-forming nanoparticles as anticancer prodrug and drug carriers:in vitro and in vivo effects.Nanomedicine (Lond).6, 855-865.
4. Duan J, Zhang Y, Han S, Chen Y, Li B, Liao M, Chen W, Deng X, Zhao J, Huang B.,2010. Synthesis and in vitro/in vivo anti-cancer evaluation of curcumin-loaded chitosan/poly (butyl cyanoacrylate) nanoparticles. Int J Pharm.1-2,211-220.
5. Anand P, Nair HB, Sung B, Kunnumakkara AB, Yadav VR, Tekmal RR, Aggarwal BB.,2010. Design of curcumin-loaded PLGA nanoparticles formulation with enhanced cellular uptake, and increased bioactivity in vitro and superior bioavailability in vivo. Biochem Pharmacol.3,330-338.
6. Yallapu MM, Maher DM, Sundram V, Bell MC, Jaggi M, Chauhan SC.,2010. Curcumin induces chemo/radio-sensitization in ovarian cancer cells and curcumin nanoparticles inhibit ovarian cancer cell growth. J Ovarian Res.29,11.
7. Xinna Wang, Xinshu Xia, Chuanshan Xu, Jing Xu, Ping Wang, Junyan Xiang, Dingqun Bai, Wingnang Leung A.2011. Ultrasound-induced cell death of nasopharyngeal carcinoma cells in the presence of curcumin. Integr Cancer Ther. 1,70-76.
8. Yau, K.Y., Dubuc, G., Li, S., Hirama, T., Mackenzie, C.R., Jermutus, L., Hall, J.C., Tanha, J.,2005.Affinity maturation of a VHH by mutational hotspot randomization. J. Immunol. Methods.297,213-224
9. Onoue S, Takahashi H, Kawabata Y, Seto Y, Hatanaka J, Timmermann B, Yamada S.,2010. Formulation design and photochemical studies on nanocrystal solid dispersion of curcumin with improved oral bioavailability. J Pharm Sci.4, 1871-1881.
10. Hegge AB, Andersen T, Melvik JE, Kristensen S, Tonnesen HH.,2010. Evaluation of novel alginate foams as drug delivery systems in antimicrobial photodynamic therapy (aPDT) of infected wounds--an in vitro study:studies on curcumin and curcuminoides XL. J Pharm Sci.8,3499-3513.
11. Hegge AB, Andersen T, Melvik JE, Bruzell E, Kristensen S, Tonnesen HH.,2011. Formulation and bacterial phototoxicity of curcumin loaded alginate foams for wound treatment applications:studies on curcumin and curcuminoides XLII. J Pharm Sci.1,174-185.
12. Manju S, Sreenivasan K.,2011. Synthesis and characterization of a cytotoxic cationic polyvinylpyrrolidone-curcumin conjugate. J Pharm Sci.2,504-511.
13. Huang Q, Yu H, Ru Q.,2010. Bioavailability and delivery of nutraceuticals using nanotechnology. J Food Sci.1,50-57.
14. Yen FL, Wu TH, Tzeng CW, Lin LT, Lin CC.,2010. Curcumin nanoparticles improve the physicochemical properties of curcumin and effectively enhance its antioxidant and antihepatoma activities. J Agric Food Chem.12,7376-7382.
15. Simoni E, Bergamini C, Fato R, Tarozzi A, Bains S, Motterlini R, Cavalli A, Bolognesi ML, Minarini A, Hrelia P, Lenaz G, Rosini M, Melchiorre C.,2010. Polyamine conjugation of curcumin analogues toward the discovery of mitochondria-directed neuroprotective agents. Med Chem.19,7264-7268.
16. Nair HB, Sung B, Yadav VR, Kannappan R, Chaturvedi MM, Aggarwal BB., 2010.Delivery of antiinflammatory nutraceuticals by nanoparticles for the prevention and treatment of cancer. Biochem Pharmacol.12,1833-1843.
17. Shehzad A, Wahid F, Lee YS.,2010. Curcumin in cancer chemoprevention: molecular targets, pharmacokinetics, bioavailability, and clinical trials.Arch Pharm (Weinheim).343,489-499.
18. Talavera A, Eriksson A, Okvist M, Lopez-Requena A, Fernandez-Marrero Y, Perez R, Moreno E, Krengel U,2009. Crystal structure of an anti-ganglioside antibody, and modelling of the functional mimicry of its NeuGc-GM3 antigen by an anti-idiotypic antibody. Mol Immunol.46,3466-3475.
19. Lin L, Deangelis S, Foust E, Fuchs J, Li C, Li PK, Schwartz EB, Lesinski GB, Benson D, Lu J, Hoyt D, Lin J.,2010. A novel small molecule inhibits STAT3 phosphorylation and DNA binding activity and exhibits potent growth suppressive activity in human cancer cells. Mol Cancer.16; 217.
20. Hegge AB, Andersen T, Melvik JE, Kristensen S, T(?)nnesen HH.,2010. Evaluation of novel alginate foams as drug delivery systems in antimicrobial photodynamic therapy (aPDT)of infected wounds--an in vitro study:studies on curcumin and curcuminoides XL. J Pharm Sci.8,3499-3513.
21. Hegge AB, Andersen T, Melvik JE, Bruzell E, Kristensen S, T(?)nnesen HH.,2011. Formulation and bacterial phototoxicity of curcumin loaded alginate foams for wound treatment applications:studies on curcumin and curcuminoides XLII. J Pharm Sci. Jan.1,174-185.
22. Dandekar PP, Jain R, Patil S, Dhumal R, Tiwari D, Sharma S, Vanage G, Patravale V.,2010. Dec; Curcumin-loaded hydrogel nanoparticles:application in anti-malarial therapy and toxicological evaluation. Pharm Sci.12,4992-5010.
23. Manju S, Sreenivasan K.,2011. Synthesis and characterization of a cytotoxic cationic polyvinylpyrrolidone-curcumin conjugate. J Pharm Sci.2,504-511.
24. Xinna Wang, Xinshu Xia, Chuanshan Xu, Jing Xu, Ping Wang, Junyan Xiang, Dingqun Bai, Wingnang Leung A.,2011. Ultrasound-induced cell death of nasopharyngeal carcinoma cells in the presence of curcumin. Integr Cancer Ther. 1,70-76.
25. Wang F, Huang W, Zhang Y, Wang M, Sun L, Tang B, Wang W.,2011. Determination of protein by fluorescence enhancement of curcumin in lanthanum-curcumin-sodium dodecyl benzene sulfonate-protein system. J Fluoresc.1,25-34.
26. Heng MC.2010. Curcumin targeted signaling pathways:basis for anti-photoaging and anti-carcinogenic therapy. Int J Dermatol.6,608-622.
27. Rowe DL, Ozbay T, O'Regan RM, Nahta R.,2009. Modulation of the BRCA1 protein and induction of apoptosis in triple negative breast cancer cell lines by the polyphenolic compound curcumin. Breast Cancer.3,61-75.
28. Yen FL, Wu TH, Tzeng CW, Lin LT, Lin CC.,2010.Curcumin nanoparticles improve the physicochemical properties of curcumin and effectively enhance its antioxidant and antihepatoma activities. J Agric Food Chem.58,7376-82.
29. Zheng Z, Zhang X, Carbo D, Clark C, Nathan C, Lvov Y.,2010. Sonication-assisted synthesis of polyelectrolyte-coated curcumin nanoparticles. Langmuir.11,7679-7681.
30. Agrawal DK, Mishra PK.,2010.Curcumin and its analogues:potential anticancer agents. Med Res Rev.30,818-860.
31. Chwilkowska A, Kulbacka J, Saczko J.,2011. Death of tumor cells. Photodynamic reaction in apoptosis induction in cancer cells. Pol Merkur Lekarski.30,45-48.
32. Ran C, Zhang Z, Hooker J, Moore A.,2011. In Vivo Photoactivation Without "Light":Use of Cherenkov Radiation to Overcome the Penetration Limit of Light. Mol Imaging Biol. May 3.
33. Ritter CG, Kuhl IC, Lenhardt C, Weissbluth ML, Bakos RM.2010. Photodynamic therapy with delta-aminolevulinic acid and light-emitting diodes in actinic keratosis.An Bras Dermatol.5,639-645.
34. Bhowmick R, Girotti AW.,2011. Rapid upregulation of cytoprotective nitric oxide in breast tumor cells subjected to a photodynamic therapy-like oxidative challenge.Photochem Photobiol.87,78-86.
35.许川山, Albert Wing, NangLeung,中药姜黄素的光谱学特性研究,激光杂志,2005年第26卷第4期。
36.许川山,Albert Wing, NangLeung,中药光敏剂介导的光动力疗,激光杂志,2004年第25卷第6期。
37.吕庆銮,张苗,岳宁宁,宫斌,王怀友,荧光探针法研究铜离子102姜黄素体系中021-的反应机理及在02存在下02的测定,高等学校化学学报,2009年第三期。
38.孙晶,季宇彬,新型姜黄素脂质体的制备和初步稳定性考察,2008年第十卷第四期。
39.刘仲荣,杨慧兰,皮肤病光动力疗法系列讲座(二)光敏剂的研究进展,中国美容医学,2009年4月18卷4期。
40.张苗,吕庆銮,岳宁宁,王怀友,酶催化-荧光猝灭法测定药物中的姜黄素,化学分析计量,2008年第17卷第6期。
41.施文荣,刘艳,姜黄素诱导人胃腺癌BGC-823细胞凋亡的光动力学研究,中华中医药学刊,2009年第27卷第9期。
42.吴晓健,吴凯南,董蒲江,姜黄素诱导人乳腺癌MCF27细胞凋亡的研究,重庆医学,2005年12月第34卷第12期。
43.回学军,孙冬,于庭,李树岩,吴东辉,姜黄素诱导K562细胞凋亡及其对细胞周期各时相影响,中国实验诊断学,2008年7月第12卷第7期。
44.霍红梅,张利元,江家贵,朱旬,姜黄素抑制乳腺癌MCF27细胞增殖及其相关的氧化应激机制,中国肿瘤生物治疗杂志,2009年十月第16卷第五期5。
45.宋洪杰,张玉梅,高丽红,姜黄素无水乙醇溶液的光稳定性研究,中国药学杂志,2009年3月第44卷第6期。
46.孙黎,刘正泉,罗强,薄爱华,姜黄素体外诱导人乳腺癌MCF27细胞凋亡作用,河北北方医学学院学报；2009年8月第26卷第四期。
47.张庆云,莫曾南,姜黄素生物利用度研究进展,China Pharmacy,2009 Vol.20 No.33。
48.李石伟,刘跃明,姜黄素联合热疗对Hep22细胞凋亡及细胞周期的影响,ChinJ Lab Diagn,November,2009,Vol 13, No.11。
49.王双玲,陈元玉,何顺华,刘峰,李冠武,姜黄素抗急性白血病机制研究,汕头大学医学院学报,2008年。
50. Kunnumakkara AB, Anand P, Aggarwal BB.,2008. Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett.269,99-225.
51. Anand P, Nair HB, Sung B, Kunnumakkara AB, Yadav VR, Tekmal RR, Aggarwal BB.,2010. Design of curcumin-loaded PLGA nanoparticles formulation with enhanced cellular uptake, and increased bioactivity in vitro and superior bioavailability in vivo.Biochem Pharmacol.79,30-38.