A preliminary discussion on establishment of patient-derived tumor xenograft (PDTX) model and testing of pharmacodynamics_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

 ZHOU Yong ¹ , HE Xiaofeng ¹ , ZHU Yanping ² , HAO Yanpeng ² , WANG Li ² , WANG Zhiqiang ²

1. Department of Thoracic and Cardiovascular Surgery, Nanjing Drum Tower Hospital, Medical College of Nanjing University, Nanjing, 210008, P.R.China;
2. Nanjing Personal Onocology Co., Ltd, Nanjing, 210008, P.R.China;

Corresponding author：

ZHOU Yong, Email: 13405858786@163.com

Keywords：

Chest tumor; patient-derived tumor xenograft (PDTX); xenotransplantation model

DOI：

10.7507/1007-4848.201709019

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To establish a patient-derived tumor xenograft (PDTX) model and to observe the latency and rate of tumor formation, tumor size, tumor invasion and metastasis of transplanted tumors. Methods Seven patients with chest tumor in Drum Tower Hospital from April to December 2015 were chosen. There were 5 males and 2 females with age ranging from 61-71 years, including 4 patients of esophageal tumor and 3 patients of lung tumor. PDTX model was established by surgical removal of fresh tumor tissues of these patients and transplantation in NOD-Prkdcem26Il2rgem26Nju subcutaneous (NCG) mice. The latency and rate of tumor formation, tumor size, tumor invasion and metastasis of transplanted tumors were observed, and pathology of HE staining and immunohistochemical testing results were compared between PDTX model and the patients. Results PDTX model was successfully established in 4 patients, and the success rate was 66.7%, including 2 patients of esophageal cancer. The PDTX model retained the differentiation, morphological and structural characteristics of original tumors. Conclusion Pathology and molecular biology characteristics of PDTX model are consistent with the original tumor, which can be an " avatar” of tumor patients for clinical pharmacodynamics screening and new drug research and development.

Citation： ZHOU Yong, HE Xiaofeng, ZHU Yanping, HAO Yanpeng, WANG Li, WANG Zhiqiang. A preliminary discussion on establishment of patient-derived tumor xenograft (PDTX) model and testing of pharmacodynamics. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2018, 25(9): 804-808. doi: 10.7507/1007-4848.201709019 Copy

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2.	Kopetz S, Lemos R, Powis G, et al. The promise of patient-derived xenografts: the best laid plans of mice and men. Clin Cancer Res, 2012, 18(19): 5160-2.
3.	Hao C, Wang L, Peng S, et al. Gene mutations in primary tumors and corresponding patient-derived xenografts derived from non-small cell lung cancer. Cancer Lett, 2015, 357(1): 179-185.
4.	Yoko S, Wang G, Lin Y, et al. Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomes. Nat Med, 2013, 17(11): 1514-1520.
5.	Zhu Y, Tian T, Li Z, et al. Establishment and characterization of patient-derived tumor xenograft using gastroscopic biopsies in gastric cancer. Sci. Rep, 2015, 10(5): 8542.
6.	Gu Q, Zhang B, Sun H, et al. Genomic characterization of a large panel of patient-derived hepatocellular carcinoma xenograft tumor models for preclinical development. Oncotarget, 2015, 6(24): 20160-20176.
7.	Zhang X, Zhang J, Wang Y, et al. Establishment of patient-derived non-small cell lung cancer xenograft models with genetic aberrations within EGFR, KRAS and FGFR1: useful tools for preclinical studies of targeted therapies. J Transl Med, 2013, 11: 168.
8.	Fichtner I, Rolff J, Soong R, et al. Establishment of patient-derived non-small cell lung cancer xenografts as modeles for the identification of predictive biomarkers. Clin Cancer Res, 2008, 14(20): 6456-6468.
9.	John T, Kohler D, Pintilie M, et al. The ability to form primary tumor xenografts is predictive of increased risk of disease recurrence in early-stage non-small cell lung cancer. Clin Cancer Res, 2011, 17(1): 134-141.
10.	Wade C, Michael B, Jorge A, et al. Initiation and characterization of small cell lung cancer patient-derived xenografts from ultrasound-guided transbronchial needle aspirates. PloS One, 2015, 10(5): e0125255.
11.	Dodbiba L, Teichman J, Fleet A, et al. Primary esophageal and gastro-esophageal junction cancer xenograft 165 models: clinicopathological features and engraftment. Lab Invest, 2013, 93(4): 397-407.
12.	Malaney P, Nicosia SV, Davé V, et al. One mouse, one patient paradigm: New avatars of personalized cancer therapy. Cancer Lett, 2014, 344(1): 1-12.
13.	Tentler JJ, Tan AC, Weekes CD, et al. Patient-derived tumour xenografts as models for oncology drug development. Nat Rev Clin Oncol, 2012, 9(6): 338-350.
14.	Julien S, Merino-Trigo A, Lacroix L, et al. Characterization of a large panel of patient-derived tumor xenografts representing the clinical heterogeneity of human colorectal cancer. Clin Cancer Res, 2012, 18(19): 5314-5428.
15.	Scott C, Becker M, Haluska P, et al. Patient-derived xenograft models to improve targeted therapy in epithelial ovarian cancer treatment. Front Oncol, 2013, 3(2): 295.
16.	Siolas D, Hannon GJ. Patient-derived tumor xenografts: transforming clinical samples into mouse models. Cancer Res, 2013, 73(17): 5315-5319.
17.	刘情, 郑琳, 张灏, 等. 人源性肿瘤组织异种移植模型的研究进展. 转化医学杂志, 2014, 3(2): 65-68.
18.	Rosfjord E, Lucas J, Li G, et al. Advances in patient-derived tumor xenografts: from target identification to predicting clinical response rates in oncology. Biochem Pharmacol, 2014, 91(2): 135-143.

1. Sjöblom T, Jones S, Wood LD, et al. The consensus coding sequences of human breast and colorectal cancers. Science, 2006, 314(5797): 268-274.
2. Kopetz S, Lemos R, Powis G, et al. The promise of patient-derived xenografts: the best laid plans of mice and men. Clin Cancer Res, 2012, 18(19): 5160-2.
3. Hao C, Wang L, Peng S, et al. Gene mutations in primary tumors and corresponding patient-derived xenografts derived from non-small cell lung cancer. Cancer Lett, 2015, 357(1): 179-185.
4. Yoko S, Wang G, Lin Y, et al. Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomes. Nat Med, 2013, 17(11): 1514-1520.
5. Zhu Y, Tian T, Li Z, et al. Establishment and characterization of patient-derived tumor xenograft using gastroscopic biopsies in gastric cancer. Sci. Rep, 2015, 10(5): 8542.
6. Gu Q, Zhang B, Sun H, et al. Genomic characterization of a large panel of patient-derived hepatocellular carcinoma xenograft tumor models for preclinical development. Oncotarget, 2015, 6(24): 20160-20176.
7. Zhang X, Zhang J, Wang Y, et al. Establishment of patient-derived non-small cell lung cancer xenograft models with genetic aberrations within EGFR, KRAS and FGFR1: useful tools for preclinical studies of targeted therapies. J Transl Med, 2013, 11: 168.
8. Fichtner I, Rolff J, Soong R, et al. Establishment of patient-derived non-small cell lung cancer xenografts as modeles for the identification of predictive biomarkers. Clin Cancer Res, 2008, 14(20): 6456-6468.
9. John T, Kohler D, Pintilie M, et al. The ability to form primary tumor xenografts is predictive of increased risk of disease recurrence in early-stage non-small cell lung cancer. Clin Cancer Res, 2011, 17(1): 134-141.
10. Wade C, Michael B, Jorge A, et al. Initiation and characterization of small cell lung cancer patient-derived xenografts from ultrasound-guided transbronchial needle aspirates. PloS One, 2015, 10(5): e0125255.
11. Dodbiba L, Teichman J, Fleet A, et al. Primary esophageal and gastro-esophageal junction cancer xenograft 165 models: clinicopathological features and engraftment. Lab Invest, 2013, 93(4): 397-407.
12. Malaney P, Nicosia SV, Davé V, et al. One mouse, one patient paradigm: New avatars of personalized cancer therapy. Cancer Lett, 2014, 344(1): 1-12.
13. Tentler JJ, Tan AC, Weekes CD, et al. Patient-derived tumour xenografts as models for oncology drug development. Nat Rev Clin Oncol, 2012, 9(6): 338-350.
14. Julien S, Merino-Trigo A, Lacroix L, et al. Characterization of a large panel of patient-derived tumor xenografts representing the clinical heterogeneity of human colorectal cancer. Clin Cancer Res, 2012, 18(19): 5314-5428.
15. Scott C, Becker M, Haluska P, et al. Patient-derived xenograft models to improve targeted therapy in epithelial ovarian cancer treatment. Front Oncol, 2013, 3(2): 295.
16. Siolas D, Hannon GJ. Patient-derived tumor xenografts: transforming clinical samples into mouse models. Cancer Res, 2013, 73(17): 5315-5319.
17. 刘情, 郑琳, 张灏, 等. 人源性肿瘤组织异种移植模型的研究进展. 转化医学杂志, 2014, 3(2): 65-68.
18. Rosfjord E, Lucas J, Li G, et al. Advances in patient-derived tumor xenografts: from target identification to predicting clinical response rates in oncology. Biochem Pharmacol, 2014, 91(2): 135-143.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

A preliminary discussion on establishment of patient-derived tumor xenograft (PDTX) model and testing of pharmacodynamics

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