共 38 条
Inhibition of curcumin on myeloid-derived suppressor cells is requisite for controlling lung cancer
被引:58
作者:

Liu, Dan
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Nanjing Univ, Sch Med, Div Immunol, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China Nanjing Univ, Sch Med, Div Immunol, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China

You, Ming
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Nanjing Univ, Sch Med, Div Immunol, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China Nanjing Univ, Sch Med, Div Immunol, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China

Xu, Yujun
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Nanjing Univ, Sch Med, Div Immunol, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China Nanjing Univ, Sch Med, Div Immunol, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China

Li, Fanlin
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Nanjing Univ, Sch Med, Div Immunol, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China Nanjing Univ, Sch Med, Div Immunol, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China

Zhang, Dongya
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Nanjing Univ, Sch Med, Div Immunol, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China Nanjing Univ, Sch Med, Div Immunol, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China

Li, Xiujun
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机构:
Nanjing Univ, Sch Med, Div Immunol, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China Nanjing Univ, Sch Med, Div Immunol, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China

Hou, Yayi
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h-index: 0
机构:
Nanjing Univ, Sch Med, Div Immunol, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China
Jiangsu Key Lab Mol Med, Nanjing 210093, Jiangsu, Peoples R China Nanjing Univ, Sch Med, Div Immunol, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China
机构:
[1] Nanjing Univ, Sch Med, Div Immunol, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China
[2] Jiangsu Key Lab Mol Med, Nanjing 210093, Jiangsu, Peoples R China
基金:
中国国家自然科学基金;
关键词:
Lung cancer;
Curcumin;
Myeloid-derived suppressor cells (MDSCs);
TUMOR MICROENVIRONMENT;
IMMUNE SUPPRESSION;
SIGNALING PATHWAY;
DNA-DAMAGE;
MODEL;
PROGRESSION;
INFLAMMATION;
MECHANISMS;
EXPRESSION;
CARCINOMA;
D O I:
10.1016/j.intimp.2016.07.035
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
摘要:
Lung cancer remains the leading cause of cancer mortality. Myeloid-derived suppressor cells (MDSCs) are potent immune-suppressive cells and present in most cancer patients. Recently, several studies have shown that curcumin inhibits the expansion of MDSCS in some cancers. However, it is not clear how curcumin modulates the suppressive function of MDSCs, and whether curcumin achieves anti-tumor effects via regulating the expansion of MDSCs in lung cancer. Here, our results showed that curcumin significantly inhibited tumor growth in a Lewis lung carcinoma (LLC) isogenic tumor model. Curcumin reduced the accumulation of MDSCs in spleen and tumor tissue in LLC isogenic model. And curcumin promoted the maturation and differentiation of MDSCs in tumor tissue. Notably, curcumin inhibited the expression level of immune suppressive factors of MDSCs, arginase-1 (Arg-1) and ROS, in purified MDSCS from tumor tissue in vivo. Expectedly, curcumin also inhibited the immunosuppressive function of isolated MDSCs from tumor tissue and spleen of tumor bearing mice in vitro. Moreover, curcumin decreased the level of IL-6 in the tumor tissue and serum from LLC-bearing mice. Taken together, curcumin indeed possesses anti-cancer effect and inhibits the accumulation and function of MDSCs. And curcumin reduces the level of IL-6 in tumor-bearing mice to impair the expansion and function of MDSCs. These results suggest that inhibition of MDSCs in tumor is requisite for controlling lung cancer. (C) 2016 Elsevier B.V. All rights reserved.
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页码:265 / 272
页数:8
相关论文
共 38 条
[1]
ESTABLISHMENT OF A CLONED LINE OF LEWIS LUNG-CARCINOMA CELLS ADAPTED TO CELL-CULTURE
[J].
BERTRAM, JS
;
JANIK, P
.
CANCER LETTERS,
1980, 11 (01)
:63-73

BERTRAM, JS
论文数: 0 引用数: 0
h-index: 0
机构:
NEW YORK STATE DEPT HLTH,ROSWELL PK MEM INST,GRACE CANC DRUG CTR,BUFFALO,NY 14263 NEW YORK STATE DEPT HLTH,ROSWELL PK MEM INST,GRACE CANC DRUG CTR,BUFFALO,NY 14263

JANIK, P
论文数: 0 引用数: 0
h-index: 0
机构:
NEW YORK STATE DEPT HLTH,ROSWELL PK MEM INST,GRACE CANC DRUG CTR,BUFFALO,NY 14263 NEW YORK STATE DEPT HLTH,ROSWELL PK MEM INST,GRACE CANC DRUG CTR,BUFFALO,NY 14263
[2]
Immune therapy of non-small cell lung cancer. The future
[J].
Bobbio, Antonio
;
Alifano, Marco
.
PHARMACOLOGICAL RESEARCH,
2015, 99
:217-222

Bobbio, Antonio
论文数: 0 引用数: 0
h-index: 0
机构:
Paris Ctr Univ Hosp, AP HP, Dept Thorac Surg, Paris, France Paris Ctr Univ Hosp, AP HP, Dept Thorac Surg, Paris, France

论文数: 引用数:
h-index:
机构:
[3]
Reduced inflammation in the tumor microenvironment delays the accumulation of myeloid-derived suppressor cells and limits tumor progression
[J].
Bunt, Stephanie K.
;
Yang, Linglin
;
Sinha, Pratima
;
Clements, Virginia K.
;
Leips, Jeff
;
Ostrand-Rosenberg, Suzanne
.
CANCER RESEARCH,
2007, 67 (20)
:10019-10026

Bunt, Stephanie K.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Maryland, Dept Biol Sci, Baltimore, MD 21250 USA Univ Maryland, Dept Biol Sci, Baltimore, MD 21250 USA

Yang, Linglin
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Maryland, Dept Biol Sci, Baltimore, MD 21250 USA Univ Maryland, Dept Biol Sci, Baltimore, MD 21250 USA

Sinha, Pratima
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Maryland, Dept Biol Sci, Baltimore, MD 21250 USA Univ Maryland, Dept Biol Sci, Baltimore, MD 21250 USA

Clements, Virginia K.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Maryland, Dept Biol Sci, Baltimore, MD 21250 USA Univ Maryland, Dept Biol Sci, Baltimore, MD 21250 USA

Leips, Jeff
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Maryland, Dept Biol Sci, Baltimore, MD 21250 USA Univ Maryland, Dept Biol Sci, Baltimore, MD 21250 USA

Ostrand-Rosenberg, Suzanne
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Maryland, Dept Biol Sci, Baltimore, MD 21250 USA Univ Maryland, Dept Biol Sci, Baltimore, MD 21250 USA
[4]
IL-6-stimulated CD11b+CD14+HLA-DR- myeloid-derived suppressor cells, are associated with progression and poor prognosis in squamous cell carcinoma of the esophagus
[J].
Chen, Miao-Fen
;
Kuan, Feng-Che
;
Yen, Tzu-Chen
;
Lu, Ming-Shian
;
Lin, Paul-Yang
;
Chung, Yi-Hsiu
;
Chen, Wen-Cheng
;
Lee, Kuan-Der
.
ONCOTARGET,
2014, 5 (18)
:8716-8728

Chen, Miao-Fen
论文数: 0 引用数: 0
h-index: 0
机构:
Chang Gung Mem Hosp, Dept Radiat Oncol, Chiayi, Taiwan
Chang Gung Univ, Coll Med, Taoyuan, Taiwan Chang Gung Mem Hosp, Dept Radiat Oncol, Chiayi, Taiwan

Kuan, Feng-Che
论文数: 0 引用数: 0
h-index: 0
机构:
Chang Gung Univ, Coll Med, Taoyuan, Taiwan
Chang Gung Mem Hosp, Chiayi, Taiwan Chang Gung Mem Hosp, Dept Radiat Oncol, Chiayi, Taiwan

Yen, Tzu-Chen
论文数: 0 引用数: 0
h-index: 0
机构:
Chang Gung Mem Hosp, Dept Nucl Med, Linkou, Taiwan
Chang Gung Mem Hosp, Ctr Adv Mol Imaging & Translat, Linkou, Taiwan Chang Gung Mem Hosp, Dept Radiat Oncol, Chiayi, Taiwan

Lu, Ming-Shian
论文数: 0 引用数: 0
h-index: 0
机构:
Chang Gung Mem Hosp, Chiayi, Taiwan Chang Gung Mem Hosp, Dept Radiat Oncol, Chiayi, Taiwan

Lin, Paul-Yang
论文数: 0 引用数: 0
h-index: 0
机构:
Chang Gung Mem Hosp, Chiayi, Taiwan Chang Gung Mem Hosp, Dept Radiat Oncol, Chiayi, Taiwan

Chung, Yi-Hsiu
论文数: 0 引用数: 0
h-index: 0
机构:
Chang Gung Mem Hosp, Ctr Adv Mol Imaging & Translat, Linkou, Taiwan Chang Gung Mem Hosp, Dept Radiat Oncol, Chiayi, Taiwan

Chen, Wen-Cheng
论文数: 0 引用数: 0
h-index: 0
机构:
Chang Gung Univ, Coll Med, Taoyuan, Taiwan Chang Gung Mem Hosp, Dept Radiat Oncol, Chiayi, Taiwan

Lee, Kuan-Der
论文数: 0 引用数: 0
h-index: 0
机构:
Chang Gung Univ, Coll Med, Taoyuan, Taiwan
Chang Gung Mem Hosp, Chiayi, Taiwan Chang Gung Mem Hosp, Dept Radiat Oncol, Chiayi, Taiwan
[5]
Curcumin alters gene expression-associated DNA damage, cell cycle, cell survival and cell migration and invasion in NCI-H460 human lung cancer cells in vitro
[J].
Chiang, I-Tsang
;
Wang, Wei-Shu
;
Liu, Hsin-Chung
;
Yang, Su-Tso
;
Tang, Nou-Ying
;
Chung, Jing-Gung
.
ONCOLOGY REPORTS,
2015, 34 (04)
:1853-1874

论文数: 引用数:
h-index:
机构:

Wang, Wei-Shu
论文数: 0 引用数: 0
h-index: 0
机构:
Natl Yang Ming Univ Hosp, Dept Internal Med, Yilan 260, Taiwan Natl Yang Ming Univ Hosp, Dept Radiat Oncol, Yilan 260, Taiwan

Liu, Hsin-Chung
论文数: 0 引用数: 0
h-index: 0
机构:
China Med Univ, Dept Biol Sci & Technol, Taichung 404, Taiwan Natl Yang Ming Univ Hosp, Dept Radiat Oncol, Yilan 260, Taiwan

Yang, Su-Tso
论文数: 0 引用数: 0
h-index: 0
机构:
China Med Univ Hosp, Dept Radiol, Taichung 404, Taiwan Natl Yang Ming Univ Hosp, Dept Radiat Oncol, Yilan 260, Taiwan

Tang, Nou-Ying
论文数: 0 引用数: 0
h-index: 0
机构:
China Med Univ, Grad Inst Chinese Med, Taichung 404, Taiwan Natl Yang Ming Univ Hosp, Dept Radiat Oncol, Yilan 260, Taiwan

论文数: 引用数:
h-index:
机构:
[6]
Curcumin and cancer: barriers to obtaining a health claim
[J].
Devassy, Jessay G.
;
Nwachukwu, Ifeanyi D.
;
Jones, Peter J. H.
.
NUTRITION REVIEWS,
2015, 73 (03)
:155-165

Devassy, Jessay G.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Manitoba, Dept Human Nutr Sci, Winnipeg, MB R3T 2N2, Canada Univ Manitoba, Dept Human Nutr Sci, Winnipeg, MB R3T 2N2, Canada

Nwachukwu, Ifeanyi D.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Manitoba, Dept Human Nutr Sci, Winnipeg, MB R3T 2N2, Canada Univ Manitoba, Dept Human Nutr Sci, Winnipeg, MB R3T 2N2, Canada

Jones, Peter J. H.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Manitoba, Dept Human Nutr Sci, Winnipeg, MB R3T 2N2, Canada
Univ Manitoba, Richardson Ctr Funct Foods & Nutraceut, Winnipeg, MB R3T 2N2, Canada Univ Manitoba, Dept Human Nutr Sci, Winnipeg, MB R3T 2N2, Canada
[7]
Myeloid derived suppressor cells-An overview of combat strategies to increase immunotherapy efficacy
[J].
Draghiciu, Oana
;
Lubbers, Joyce
;
Nijman, Hans W.
;
Daemen, Toos
.
ONCOIMMUNOLOGY,
2015, 4 (01)
:954829

Draghiciu, Oana
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Groningen, Univ Med Ctr Groningen, Dept Med Microbiol Tumor Virol & Canc Immunothera, Groningen, Netherlands Univ Groningen, Univ Med Ctr Groningen, Dept Med Microbiol Tumor Virol & Canc Immunothera, Groningen, Netherlands

Lubbers, Joyce
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Groningen, Univ Med Ctr Groningen, Dept Med Microbiol Tumor Virol & Canc Immunothera, Groningen, Netherlands Univ Groningen, Univ Med Ctr Groningen, Dept Med Microbiol Tumor Virol & Canc Immunothera, Groningen, Netherlands

Nijman, Hans W.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Groningen, Univ Med Ctr Groningen, Dept Gynecol, Groningen, Netherlands Univ Groningen, Univ Med Ctr Groningen, Dept Med Microbiol Tumor Virol & Canc Immunothera, Groningen, Netherlands

Daemen, Toos
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Groningen, Univ Med Ctr Groningen, Dept Med Microbiol Tumor Virol & Canc Immunothera, Groningen, Netherlands Univ Groningen, Univ Med Ctr Groningen, Dept Med Microbiol Tumor Virol & Canc Immunothera, Groningen, Netherlands
[8]
Curcumin inhibits the invasion of lung cancer cells by modulating the PKCα/Nox-2/ROS/ATF-2/MMP-9 signaling pathway
[J].
Fan, Zhigang
;
Duan, Xiaoyi
;
Cai, Hui
;
Wang, Li
;
Li, Min
;
Qu, Jingkun
;
Li, Wanjun
;
Wang, Yongheng
;
Wang, Jiansheng
.
ONCOLOGY REPORTS,
2015, 34 (02)
:691-698

Fan, Zhigang
论文数: 0 引用数: 0
h-index: 0
机构:
Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Thorac Surg 2, Xian 710049, Shaanxi, Peoples R China
Xi An Jiao Tong Univ, Hosp 3201, Dept Oncol, Hanzhong, Shaanxi, Peoples R China Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Thorac Surg 2, Xian 710049, Shaanxi, Peoples R China

Duan, Xiaoyi
论文数: 0 引用数: 0
h-index: 0
机构:
Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Nucl Med, Xian 710049, Shaanxi, Peoples R China Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Thorac Surg 2, Xian 710049, Shaanxi, Peoples R China

Cai, Hui
论文数: 0 引用数: 0
h-index: 0
机构:
Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Thorac Surg 2, Xian 710049, Shaanxi, Peoples R China
Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Anesthesia, Xian 710049, Shaanxi, Peoples R China Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Thorac Surg 2, Xian 710049, Shaanxi, Peoples R China

Wang, Li
论文数: 0 引用数: 0
h-index: 0
机构:
Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Thorac Surg 2, Xian 710049, Shaanxi, Peoples R China
Hosp Changan Univ, Dept Internal Med, Xian, Shaanxi, Peoples R China Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Thorac Surg 2, Xian 710049, Shaanxi, Peoples R China

Li, Min
论文数: 0 引用数: 0
h-index: 0
机构:
Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Thorac Surg 2, Xian 710049, Shaanxi, Peoples R China Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Thorac Surg 2, Xian 710049, Shaanxi, Peoples R China

Qu, Jingkun
论文数: 0 引用数: 0
h-index: 0
机构:
Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Thorac Surg 2, Xian 710049, Shaanxi, Peoples R China Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Thorac Surg 2, Xian 710049, Shaanxi, Peoples R China

Li, Wanjun
论文数: 0 引用数: 0
h-index: 0
机构:
Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Thorac Surg 2, Xian 710049, Shaanxi, Peoples R China
Xi An Jiao Tong Univ, Hosp 3201, Dept Pathol, Hanzhong, Shaanxi, Peoples R China Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Thorac Surg 2, Xian 710049, Shaanxi, Peoples R China

Wang, Yongheng
论文数: 0 引用数: 0
h-index: 0
机构:
Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Thorac Surg 2, Xian 710049, Shaanxi, Peoples R China
Xi An Jiao Tong Univ, Prov Hosp, Xian 710049, Shaanxi, Peoples R China Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Thorac Surg 2, Xian 710049, Shaanxi, Peoples R China

Wang, Jiansheng
论文数: 0 引用数: 0
h-index: 0
机构:
Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Thorac Surg 2, Xian 710049, Shaanxi, Peoples R China Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Thorac Surg 2, Xian 710049, Shaanxi, Peoples R China
[9]
Curcumin inhibits angiogenesis and improves defective hematopoiesis induced by tumor-derived VEGF in tumor model through modulating VEGF-VEGFR2 signaling pathway
[J].
Fu, Zhongping
;
Chen, Xiao
;
Guan, Shengwen
;
Yan, Yanju
;
Lin, Huan
;
Hua, Zi-Chun
.
ONCOTARGET,
2015, 6 (23)
:19469-19482

Fu, Zhongping
论文数: 0 引用数: 0
h-index: 0
机构:
Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Taipa, Macau, Peoples R China
Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Nanjing, Jiangsu, Peoples R China
Jiangsu Simcere Pharmaceut R&D Co Ltd, Nanjing, Jiangsu, Peoples R China Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Taipa, Macau, Peoples R China

Chen, Xiao
论文数: 0 引用数: 0
h-index: 0
机构:
Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Nanjing, Jiangsu, Peoples R China Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Taipa, Macau, Peoples R China

Guan, Shengwen
论文数: 0 引用数: 0
h-index: 0
机构:
Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Nanjing, Jiangsu, Peoples R China
Nanjing Ind Innovat Ctr Pharmaceut Biotechnol, Nanjing, Jiangsu, Peoples R China
Nanjing Univ, Changzhou High Tech Res Inst, Changzhou, Jiangsu, Peoples R China
Targetpharma Lab, Changzhou, Jiangsu, Peoples R China Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Taipa, Macau, Peoples R China

Yan, Yanju
论文数: 0 引用数: 0
h-index: 0
机构:
Nanjing Univ, Changzhou High Tech Res Inst, Changzhou, Jiangsu, Peoples R China
Targetpharma Lab, Changzhou, Jiangsu, Peoples R China Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Taipa, Macau, Peoples R China

Lin, Huan
论文数: 0 引用数: 0
h-index: 0
机构:
Jiangsu Simcere Pharmaceut R&D Co Ltd, Nanjing, Jiangsu, Peoples R China Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Taipa, Macau, Peoples R China

Hua, Zi-Chun
论文数: 0 引用数: 0
h-index: 0
机构:
Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Taipa, Macau, Peoples R China
Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Nanjing, Jiangsu, Peoples R China
Nanjing Univ Chinese Med, Coll Pharm, Nanjing 210046, Jiangsu, Peoples R China Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Taipa, Macau, Peoples R China
[10]
Myeloid-derived suppressor cells as regulators of the immune system
[J].
Gabrilovich, Dmitry I.
;
Nagaraj, Srinivas
.
NATURE REVIEWS IMMUNOLOGY,
2009, 9 (03)
:162-174

Gabrilovich, Dmitry I.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ S Florida, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA Univ S Florida, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA

Nagaraj, Srinivas
论文数: 0 引用数: 0
h-index: 0
机构: Univ S Florida, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA