Skip to main content

Main menu

  • Home
  • Current Issue
  • Archive
  • Info for
    • Authors
    • Editorial Policies
    • Subscribers
    • Advertisers
    • Editorial Board
    • Special Issues 2025
  • Journal Metrics
  • Other Publications
    • In Vivo
    • Cancer Genomics & Proteomics
    • Cancer Diagnosis & Prognosis
  • More
    • IIAR
    • Conferences
    • 2008 Nobel Laureates
  • About Us
    • General Policy
    • Contact
  • Other Publications
    • Anticancer Research
    • In Vivo
    • Cancer Genomics & Proteomics

User menu

  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Anticancer Research
  • Other Publications
    • Anticancer Research
    • In Vivo
    • Cancer Genomics & Proteomics
  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart
Anticancer Research

Advanced Search

  • Home
  • Current Issue
  • Archive
  • Info for
    • Authors
    • Editorial Policies
    • Subscribers
    • Advertisers
    • Editorial Board
    • Special Issues 2025
  • Journal Metrics
  • Other Publications
    • In Vivo
    • Cancer Genomics & Proteomics
    • Cancer Diagnosis & Prognosis
  • More
    • IIAR
    • Conferences
    • 2008 Nobel Laureates
  • About Us
    • General Policy
    • Contact
  • Visit us on Facebook
  • Follow us on Linkedin
Research ArticleExperimental Studies

Patient-derived Orthotopic Xenograft (PDOX) Nude Mouse Model of Soft-tissue Sarcoma More Closely Mimics the Patient Behavior in Contrast to the Subcutaneous Ectopic Model

YUKIHIKO HIROSHIMA, YONG ZHANG, NAN ZHANG, FUMINARI UEHARA, ALI MAAWY, TAKASHI MURAKAMI, SUMIYUKI MII, MAKO YAMAMOTO, SHINJI MIWA, SHUYA YANO, MASASHI MOMIYAMA, RYUTARO MORI, RYUSEI MATSUYAMA, TAKASHI CHISHIMA, KUNIYA TANAKA, YASUSHI ICHIKAWA, MICHAEL BOUVET, ITARU ENDO and ROBERT M. HOFFMAN
Anticancer Research February 2015, 35 (2) 697-701;
YUKIHIKO HIROSHIMA
1AntiCancer, Inc., San Diego, CA, U.S.A.
2Department of Surgery, University of California San Diego, San Diego, CA, U.S.A.
3Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
YONG ZHANG
1AntiCancer, Inc., San Diego, CA, U.S.A.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
NAN ZHANG
1AntiCancer, Inc., San Diego, CA, U.S.A.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
FUMINARI UEHARA
1AntiCancer, Inc., San Diego, CA, U.S.A.
2Department of Surgery, University of California San Diego, San Diego, CA, U.S.A.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
ALI MAAWY
2Department of Surgery, University of California San Diego, San Diego, CA, U.S.A.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
TAKASHI MURAKAMI
1AntiCancer, Inc., San Diego, CA, U.S.A.
2Department of Surgery, University of California San Diego, San Diego, CA, U.S.A.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
SUMIYUKI MII
1AntiCancer, Inc., San Diego, CA, U.S.A.
2Department of Surgery, University of California San Diego, San Diego, CA, U.S.A.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
MAKO YAMAMOTO
1AntiCancer, Inc., San Diego, CA, U.S.A.
2Department of Surgery, University of California San Diego, San Diego, CA, U.S.A.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
SHINJI MIWA
1AntiCancer, Inc., San Diego, CA, U.S.A.
2Department of Surgery, University of California San Diego, San Diego, CA, U.S.A.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
SHUYA YANO
1AntiCancer, Inc., San Diego, CA, U.S.A.
2Department of Surgery, University of California San Diego, San Diego, CA, U.S.A.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
MASASHI MOMIYAMA
3Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
RYUTARO MORI
3Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
RYUSEI MATSUYAMA
3Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
TAKASHI CHISHIMA
3Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
KUNIYA TANAKA
3Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
YASUSHI ICHIKAWA
3Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
MICHAEL BOUVET
2Department of Surgery, University of California San Diego, San Diego, CA, U.S.A.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
ITARU ENDO
3Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
ROBERT M. HOFFMAN
1AntiCancer, Inc., San Diego, CA, U.S.A.
2Department of Surgery, University of California San Diego, San Diego, CA, U.S.A.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: all@anticancer.com
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Aim: Soft-tissue sarcomas are a group of rare mesenchymal carcinomas that include approximately 50 histological types, and account for 1% of all adult cancer cases. The yearly incidence of soft-tissue sarcomas in the USA is approximately 11,280 cases, with an overall mortality of 3,900 deaths per year. Materials and Methods: In this study, we established a patient-derived orthotopic xenograft (PDOX) from a patient with a soft-tissue sarcoma of the retroperitoneum in nude mice and compared it to a subcutaneous patient-derived model of the same tumor for histology. Results: In the PDOX model, a bulky tumor grew in the left retroperitoneum in the same manner as the patient's tumor. Upon histological examination, the majority of the PDOX tissue section comprised sarcomatous high-grade spindle cells of varying sizes, similar to the original patient tumor. In contrast, the majority of the subcutaneously-implanted tumor comprised round to oval cells. Conclusion: These results indicate that the PDOX recapitulated the histology of the original tumor more than the subcutaneous model.

  • Soft-tissue sarcoma
  • patient-derived orthotopic xenograft (PDOX)
  • subcutaneous model
  • nude mouse
  • histology
  • spindle cells

Soft-tissue sarcomas are a group of rare mesenchymal carcinomas that include approximately 50 histological types, and account for 1% of all adult cancer cases (1). The yearly incidence of soft-tissue sarcomas in the USA is approximately 11,280 cases, with an overall mortality of 3,900 deaths per year (2). The development of new systemic treatments for soft-tissue sarcomas has progressed little in the past few decades. Patients with metastatic soft-tissue sarcomas have a median overall survival of about 12 months. There is a need to find effective therapy for patients with these tumors.

Our laboratory pioneered the patient-derived orthotopic xenograft (PDOX) nude mouse model in the early 1990s (3-8) and demonstrated that the PDOX model, which uses intact tissue for orthotopic transplantation, closely mimics the patient, including the metastatic pattern. In contrast, subcutaneously-implanted patient tumor models, now given such names as “xenopatients” (9), “avatars” (10) and “tumorgrafts” (11), do not mimic the patient since they cannot metastasize. Recent studies from our laboratory have demonstrated that PDOX models can be used to develop fluorescence-guided surgery (12-14), novel therapeutics such as tumor-targeting bacteria (15) and study the tumor microenvironment (TME) (16-18).

In the present study, we established a PDOX nude mouse model with a soft-tissue sarcoma of the retroperitoneum from a patient in nude mice and compared the PDOX to a subcutaneous model for tumor growth and histology.

Materials and Methods

Animals. Male athymic nu/nu nude mice (AntiCancer Inc., San Diego, CA, USA), 4-6 weeks old, were used in this study. Mice were kept in a barrier facility under HEPA filtration. Mice were fed with autoclaved laboratory rodent diet. All mouse surgical procedures and imaging were performed with the animals anesthetized by intramuscular injection of a solution of 50% ketamine, 38% xylazine, and 12% acepromazine maleate (0.02 ml). All animal studies were conducted with an AntiCancer Institutional Animal Care and Use Committee (IACUC)-protocol specifically approved for this study and in accordance with the principals and procedures outlined in the National Institutes of Health Guide for the Care and Use of Animals under Assurance Number A3873-1.

Figure 1.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1.

Features of the patient-derived orthotopic xenograft (PDOX) model of soft-tissue sarcoma growing in nude mice. A: Laparotomy of the soft tissue sarcoma PDOX model. B: Lateral view of the laparotomy of the soft tissue sarcoma PDOX model. C: High magnification image of (B). The areas surrounded by the yellow dashed lines indicate the large primary tumor growing in the retroperitoneal space just behind the left kidney.

Specimen collection. The patient provided written informed consent and samples were procured and the study was conducted under the approval of the Institutional Review Board of the UC San Diego Medical Center.

Establishment of a PDOX of soft-tissue sarcoma. Tumor tissues were obtained from a patient with a soft-tissue sarcoma of the retroperitoneum at biopsy, cut into fragments (3-mm3) and transplanted to the retroperitoneal space behind the left kidney of nude mice. A small 6- to 10-mm transverse incision was made on the left lateral lumbar region of the mouse through the skin and muscle. Retroperitoneal fat behind the left nude-mouse kidney, corresponding to where the original tumor grew in the patient, was exposed through this incision and split to make space for implantation. A single tumor fragment (3-mm3) was inserted into this space, which was closed using 8-0 nylon surgical sutures (Ethilon; Ethicon Inc., NJ, USA). On completion, the incision was closed in one layer using 6-0 nylon surgical sutures (Ethilon; Ethicon Inc.). Similar-sized tumor fragments were also transplanted subcutaneously in nude mice using standard techniques.

Tissue histology. Seven weeks after implantation, tumor samples were removed with surrounding normal tissues at the time of resection. Fresh tissue samples were fixed in 10% formalin and embedded in paraffin before sectioning and staining. Tissue sections (5 μm) were deparaffinized in xylene and rehydrated in an ethanol series. Hematoxylin and eosin (H&E) staining was performed according to standard protocols. The sections were examined using a BH-2 microscope (Olympus, Tokyo, Japan) equipped with an INFINITY1 2.0 megapixel CMOS digital camera (Lumenera Corporation, Ottawa, Canada). All images were acquired using INFINITY ANALYZE software (Lumenera Corporation) without post-acquisition processing.

Quantitation of the number of spindle cells in tissue sections. The quantitation of cells was determined by counting cells in four different random fields in the same section at ×200 magnification using the BH-2 microscope (described above). The average number of spindle cells was calculated and data for the original patient tumor, the PDOX tumor and the subcutaneously-grown tumors were compared. Data for each tumor are represented as the mean ± SD.

Figure 2.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 2.

Histology of original tumor, patient-derived orthotopic xenograft (PDOX) model and subcutaneous-transplant model. Hematoxylin and eosin-stained sections of the patient's original tumor (A, B); PDOX tumor (C, D); and subcutaneously-grown tumor (E, F) at low (A, C, E) and high (B, D, F) magnification. Yellow arrowheads indicate sarcomatous spindle cells. White arrowheads indicate round to oval cells.

Statistical analysis. PASW Statistics 18.0 (SPSS, Inc., Quarry Bay, Hong Kong) was used for all statistical analyses. The Student's t-test was used to compare continuous variables between two groups. A p-value of 0.05 was considered statistically significant for all comparisons.

Results and Discussion

Establishment of a PDOX of soft-tissue sarcoma. Tumor tissues from a patient with a soft-tissue sarcoma of the retroperitoneum were transplanted to the retroperitoneal space behind the left kidney of nude mice. Eight weeks after implantation, a bulky tumor was found growing in the left retroperitoneum in the same manner as the tumor grew in the patient (Figure 1).

PDOX of soft-tissue sarcoma recapitulates the histology of the original tumor. We compared the histology of the PDOX, the subcutaneous transplant and original patient tumors of the soft-tissue sarcoma with H&E staining. The majority of the original patient tumor section was comprised of sarcomatous high-grade spindle cells of varying sizes, demonstrating abundant, finely granular cytoplasm and atypical, pleomorphic, round-to-elongated nuclei with irregular nuclear membranes, an open chromatin pattern and prominent nucleoli (Figure 2A and B). The PDOX tumor had histological structures similar to those of the original tumor (Figure 2C and D). In contrast, the majority of the subcutaneously-grown tumor tissue section was comprised of round to oval cells (Figure 2E and F). The number of spindle cells in the original tumor was 245.3±68.5; in the PDOX tumor was 177.0±11.5; and in the subcutaneous tumor section was 116.0±30.5. The number of spindle cells in the subcutaneous tumor was significantly lower compared to the original tumor and the PDOX tumor (p=0.014 and p=0.01, respectively). The percentage of spindle cells in the original tumor was 62.1±5.3; the PDOX tumor was 49.9±4.5; and the subcutaneous tumor, 28.0±4.5. The percentage of spindle cells in the subcutaneous tumor was significantly lower compared to the original tumor and the PDOX tumor (p<0.001 and p<0.001, respectively), indicating that the PDOX recapitulated the histology of the original tumor, while the subcutaneously grown tumor did not.

In conclusion, the PDOX from the patient with a soft-tissue sarcoma of the retroperitoneum was successfully established in nude mice. This is the first report of a PDOX model of soft-tissue sarcoma. Orthotopic implantation preserved the original histological structure of the patient tumor.

The results of the present report suggest caution with respect to the use of subcutaneously-grown patient tumor mouse models for directing patient therapy (9-11) or drug discovery (19) and suggestions that subcutaneous models are a “breakthrough” (20) when indeed they were developed in 1969 (21). The present results and previous publications (3-8) indicate that orthotopic mouse models are more clinically appropriate.

Acknowledgements

This study was supported in part by National Cancer Institute grant CA183280 and JSPS KAKENHI Grant Numbers 26830081 to Y.H., 26462070 to I.E and 24592009 to K.T.

Footnotes

  • Dedication

    This paper is dedicated to the memory of A. R. Moossa, M.D., and to the memory of James (Barney) Berglund, Jr., who inspired us to find improved therapy of soft-tissue sarcoma.

  • Received October 14, 2014.
  • Revision received November 4, 2014.
  • Accepted November 5, 2014.
  • Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved

References

  1. ↵
    1. Clark MA,
    2. Fisher C,
    3. Judson I,
    4. Thomas JM
    : Soft-tissue sarcomas in adults. N Engl J Med 353: 701-711, 2005.
    OpenUrlCrossRefPubMed
  2. ↵
    1. Siegel R,
    2. Naishadham D,
    3. Jemal A
    : Cancer statistics, 2012. CA Cancer J Clin 62: 10-29, 2012.
    OpenUrlCrossRefPubMed
  3. ↵
    1. Fu X,
    2. Guadagni F,
    3. Hoffman RM
    : A metastatic nude-mouse model of human pancreatic cancer constructed orthotopically with histologically intact patient specimens. Proc Natl Acad Sci USA 89: 5645-5649, 1992.
    OpenUrlAbstract/FREE Full Text
    1. Fu XY,
    2. Besterman JM,
    3. Monosov A,
    4. Hoffman RM
    : Models of human metastatic colon cancer in nude mice orthotopically constructed by using histologically intact patient specimens. Proc Natl Acad Sci USA 88: 9345-9349, 1991.
    OpenUrlAbstract/FREE Full Text
    1. Fu X,
    2. Hoffman RM
    : Human ovarian carcinoma metastatic models constructed in nude mice by orthotopic transplantation of histologically-intact patient specimens. Anticancer Res 13: 283-286, 1993.
    OpenUrlPubMed
    1. Fu X,
    2. Le P,
    3. Hoffman RM
    . A metastatic-orthotopic transplant nude-mouse model of human patient breast cancer. Anticancer Res 13: 901-904, 1993.
    OpenUrlPubMed
    1. Furukawa T,
    2. Fu X,
    3. Kubota T,
    4. Watanabe M,
    5. Kitajima M,
    6. Hoffman RM
    : Nude mouse metastatic models of human stomach cancer constructed using orthotopic implantation of histologically intact tissue. Cancer Res 53: 1204-1208, 1993.
    OpenUrlAbstract/FREE Full Text
  4. ↵
    1. Wang X,
    2. Fu X,
    3. Hoffman RM
    : A new patient-like metastatic model of human lung cancer constructed orthotopically with intact tissue via thoracotomy in immunodeficient mice. Int J Cancer 51: 992-995, 1992.
    OpenUrlPubMed
  5. ↵
    1. Bertotti A,
    2. Migliardi G,
    3. Galimi F,
    4. Sassi F,
    5. Torti D,
    6. Isella C,
    7. Corà D,
    8. Di Nicolantonio F,
    9. Buscarino M,
    10. Petti C,
    11. Ribero D,
    12. Russolillo N,
    13. Muratore A,
    14. Massucco P,
    15. Pisacane A,
    16. Molinaro L,
    17. Valtorta E,
    18. Sartore-Bianchi A,
    19. Risio M,
    20. Capussotti L,
    21. Gambacorta M,
    22. Siena S,
    23. Medico E,
    24. Sapino A,
    25. Marsoni S,
    26. Comoglio PM,
    27. Bardelli A,
    28. Trusolino L
    : A molecularly annotated platform of patient-derived xenografts (“xenopatients”) identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer. Cancer discovery 1: 508-523, 2011.
    OpenUrlAbstract/FREE Full Text
  6. ↵
    1. Dong X,
    2. Guan J,
    3. English JC,
    4. Flint J,
    5. Yee J,
    6. Evans K,
    7. Murray N,
    8. Macaulay C,
    9. Ng RT,
    10. Gout PW,
    11. Lam WL,
    12. Laskin J,
    13. Ling V,
    14. Lam S,
    15. Wang Y
    : Patient-derived first generation xenografts of non-small cell lung cancers: promising tools for predicting drug responses for personalized chemotherapy. Clin Cancer Res 16: 1442-1451, 2010.
    OpenUrlAbstract/FREE Full Text
  7. ↵
    1. DeRose YS,
    2. Wang G,
    3. Lin YC,
    4. Bernard PS,
    5. Buys SS,
    6. Ebbert MT,
    7. Factor R,
    8. Matsen C,
    9. Milash BA,
    10. Nelson E,
    11. Neumayer L,
    12. Randall RL,
    13. Stijleman IJ,
    14. Welm BE,
    15. Welm AL
    : Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomes. Nat Med 17: 1514-1520, 2011.
    OpenUrlCrossRefPubMed
  8. ↵
    1. Hiroshima Y,
    2. Maawy A,
    3. Metildi CA,
    4. Zhang Y,
    5. Uehara F,
    6. Miwa S,
    7. Yano S,
    8. Sato S,
    9. Murakami T,
    10. Momiyama M,
    11. Chishima T,
    12. Tanaka K,
    13. Bouvet M,
    14. Endo I,
    15. Hoffman RM
    : Successful fluorescence-guided surgery on human colon cancer patient-derived orthotopic xenograft mouse models using a fluorophore-conjugated anti-CEA antibody and a portable imaging system. J Laparoendosc Adv Surg Tech A 24: 241-247, 2014.
    OpenUrlPubMed
    1. Hiroshima Y,
    2. Maawy A,
    3. Sato S,
    4. Sato S,
    5. Murakami T,
    6. Uehara F,
    7. Miwa S,
    8. Yano S,
    9. Momiyama M,
    10. Chishima T,
    11. Tanaka K,
    12. Bouvet M,
    13. Endo I,
    14. Hoffman RM
    : Hand-held high-resolution fluorescence imaging system for fluorescence-guided surgery of patient and cell-line pancreatic tumors growing orthotopically in nude mice. J Surg Res 187: 510-517, 2014.
    OpenUrlPubMed
  9. ↵
    1. Hiroshima Y,
    2. Maawy A,
    3. Zhang Y,
    4. Murakami T,
    5. Momiyama M,
    6. Mori R,
    7. Matsuyama R,
    8. Katz MH,
    9. Fleming JB,
    10. Chishima T,
    11. Tanaka K,
    12. Ichikawa Y,
    13. Endo I,
    14. Hoffman RM,
    15. Bouvet M
    . Metastatic recurrence in a pancreatic cancer patient derived orthotopic xenograft (PDOX) nude mouse model is inhibited by neoadjuvant chemotherapy in combination with fluorescence-guided surgery with an anti-CA 19-9-conjugated fluorophore. PLoS One 9: e114310, 2014.
    OpenUrlPubMed
  10. ↵
    1. Hiroshima Y,
    2. Zhao M,
    3. Maawy A,
    4. Zhang Y,
    5. Katz MH,
    6. Fleming JB,
    7. Uehara F,
    8. Miwa S,
    9. Yano S,
    10. Momiyama M,
    11. Suetsugu A,
    12. Chishima T,
    13. Tanaka K,
    14. Bouvet M,
    15. Endo I,
    16. Hoffman RM
    : Efficacy of Salmonella typhimurium A1-R versus chemotherapy on a pancreatic cancer patient-derived orthotopic xenograft (PDOX). J Cell Biochem 115: 1254-1261, 2014.
    OpenUrlPubMed
  11. ↵
    1. Suetsugu A,
    2. Katz M,
    3. Fleming J,
    4. Truty M,
    5. Thomas R,
    6. Saji S,
    7. Moriwaki H,
    8. Bouvet M,
    9. Hoffman RM
    : Non-invasive fluorescent-protein imaging of orthotopic pancreatic-cancer-patient tumorgraft progression in nude mice. Anticancer Res 32: 3063-3068, 2012.
    OpenUrlAbstract/FREE Full Text
    1. Suetsugu A,
    2. Katz M,
    3. Fleming J,
    4. Truty M,
    5. Thomas R,
    6. Saji S,
    7. Moriwaki H,
    8. Bouvet M,
    9. Hoffman RM
    . Imageable fluorescent metastasis resulting in transgenic GFP mice orthotopically implanted with human-patient primary pancreatic cancer specimens. Anticancer Res 32: 1175-1180, 2012.
    OpenUrlAbstract/FREE Full Text
  12. ↵
    1. Suetsugu A,
    2. Katz M,
    3. Fleming J,
    4. Truty M,
    5. Thomas R,
    6. Saji S,
    7. Moriwaki H,
    8. Bouvet M,
    9. Hoffman RM
    . Non-invasive fluorescent-protein imaging of orthotopic pancreatic-cancer-patient tumorgraft progression in nude mice. Anticancer Res 32: 3063-3068, 2012.
    OpenUrlAbstract/FREE Full Text
  13. ↵
    1. Tentler JJ,
    2. Tan AC,
    3. Weekes CD,
    4. Jimeno A,
    5. Leong S,
    6. Pitts TM,
    7. Arcaroli JJ,
    8. Messersmith WA,
    9. Eckhardt SG
    : Patient-derived tumour xenografts as models for oncology drug development. Nat Rev Clin Oncol 9: 338-350, 2012.
    OpenUrlCrossRefPubMed
  14. ↵
    1. Couzin-Frankel J
    . The littlest patient. Science 346: 25-27, 2014.
    OpenUrl
  15. ↵
    1. Rygaard J,
    2. Poulsen CO
    . Heterotransplantation of a human malignant tumour to “nude” mice. Acta Path Microbiol Scand 77: 758-760, 1969.
    OpenUrlPubMed
PreviousNext
Back to top

In this issue

Anticancer Research: 35 (2)
Anticancer Research
Vol. 35, Issue 2
February 2015
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
  • Back Matter (PDF)
  • Ed Board (PDF)
  • Front Matter (PDF)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word on Anticancer Research.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Patient-derived Orthotopic Xenograft (PDOX) Nude Mouse Model of Soft-tissue Sarcoma More Closely Mimics the Patient Behavior in Contrast to the Subcutaneous Ectopic Model
(Your Name) has sent you a message from Anticancer Research
(Your Name) thought you would like to see the Anticancer Research web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
7 + 2 =
Solve this simple math problem and enter the result. E.g. for 1+3, enter 4.
Citation Tools
Patient-derived Orthotopic Xenograft (PDOX) Nude Mouse Model of Soft-tissue Sarcoma More Closely Mimics the Patient Behavior in Contrast to the Subcutaneous Ectopic Model
YUKIHIKO HIROSHIMA, YONG ZHANG, NAN ZHANG, FUMINARI UEHARA, ALI MAAWY, TAKASHI MURAKAMI, SUMIYUKI MII, MAKO YAMAMOTO, SHINJI MIWA, SHUYA YANO, MASASHI MOMIYAMA, RYUTARO MORI, RYUSEI MATSUYAMA, TAKASHI CHISHIMA, KUNIYA TANAKA, YASUSHI ICHIKAWA, MICHAEL BOUVET, ITARU ENDO, ROBERT M. HOFFMAN
Anticancer Research Feb 2015, 35 (2) 697-701;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Reprints and Permissions
Share
Patient-derived Orthotopic Xenograft (PDOX) Nude Mouse Model of Soft-tissue Sarcoma More Closely Mimics the Patient Behavior in Contrast to the Subcutaneous Ectopic Model
YUKIHIKO HIROSHIMA, YONG ZHANG, NAN ZHANG, FUMINARI UEHARA, ALI MAAWY, TAKASHI MURAKAMI, SUMIYUKI MII, MAKO YAMAMOTO, SHINJI MIWA, SHUYA YANO, MASASHI MOMIYAMA, RYUTARO MORI, RYUSEI MATSUYAMA, TAKASHI CHISHIMA, KUNIYA TANAKA, YASUSHI ICHIKAWA, MICHAEL BOUVET, ITARU ENDO, ROBERT M. HOFFMAN
Anticancer Research Feb 2015, 35 (2) 697-701;
Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results and Discussion
    • Acknowledgements
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • Combination of Trabectedin With Irinotecan, Leucovorin and 5-Fluorouracil Arrests Primary Colorectal Cancer in an Imageable Patient-derived Orthotopic Xenograft Mouse Model
  • Combination of Trabectedin With Oxaliplatinum and 5-Fluorouracil Arrests a Primary Colorectal Cancer in a Patient-derived Orthotopic Xenograft Mouse Model
  • Visualizing the Tumor Microenvironment by Color-coded Imaging in Orthotopic Mouse Models of Cancer
  • Cervical Cancer Patient-Derived Orthotopic Xenograft (PDOX) Is Sensitive to Cisplatinum and Resistant to Nab-paclitaxel
  • Effect of Xenotransplantation Site on MicroRNA Expression of Human Colon Cancer Stem Cells
  • Orthotopic Implantation of Intact Tumor Tissue Leads to Metastasis of OCUM-2MD3 Human Gastric Cancer in Nude Mice Visualized in Real Time by Intravital Fluorescence Imaging
  • Google Scholar

More in this TOC Section

  • CA9-Positive Keloid Fibroblasts: Modulator of Local Inflammation Induced by the Hypoxic and Glycolysis-enhanced Microenvironment
  • Predictive Factors for Multiple Metastases of Clear-cell Renal Cell Carcinoma
  • Acyclic Retinoid Overcomes Vemurafenib Resistance in Melanoma Cells via Dual Inhibition of MAPK and PI3K/AKT/mTOR Pathways
Show more Experimental Studies

Similar Articles

Keywords

  • soft-tissue sarcoma
  • patient-derived orthotopic xenograft (PDOX)
  • subcutaneous model
  • nude mouse
  • histology
  • spindle cells
Anticancer Research

© 2025 Anticancer Research

Powered by HighWire