Skip to main content

Main menu

  • Home
  • Content
    • Current
    • Archive
  • Info for
    • Authors
    • Subscribers
    • Advertisers
    • Editorial Board
  • Other Publications
    • Anticancer Research
    • Cancer Genomics & Proteomics
  • More
    • IIAR
    • Conferences
  • About Us
    • General Policy
    • Contact
  • Other Publications
    • In Vivo
    • Anticancer Research
    • Cancer Genomics & Proteomics

User menu

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

Search

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

Advanced Search

  • Home
  • Content
    • Current
    • Archive
  • Info for
    • Authors
    • Subscribers
    • Advertisers
    • Editorial Board
  • Other Publications
    • Anticancer Research
    • Cancer Genomics & Proteomics
  • More
    • IIAR
    • Conferences
  • About Us
    • General Policy
    • Contact
  • Visit iiar on Facebook
  • Follow us on Linkedin
Research ArticleExperimental Studies

A Novel Procedure for Orthotopic Tibia Implantation for Establishment of a More Clinical Osteosarcoma PDOX Mouse Model

NATHANIEL F. WU, JUN YAMAMOTO, MICHAEL BOUVET and ROBERT M. HOFFMAN
In Vivo January 2021, 35 (1) 105-109; DOI: https://doi.org/10.21873/invivo.12237
NATHANIEL F. WU
1AntiCancer Inc, San Diego, CA, U.S.A.;
2Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, U.S.A.;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
JUN YAMAMOTO
1AntiCancer Inc, San Diego, CA, U.S.A.;
3Department of Surgery, University of California, San Diego, CA, U.S.A.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
MICHAEL BOUVET
3Department of Surgery, University of California, San Diego, CA, U.S.A.
  • 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.;
3Department of Surgery, University of California, 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

Background/Aim: Osteosarcoma is a rare type of malignancy that affects mostly children and adolescents. A new procedure was designed to create an improved patient-derived orthotopic xenograft (PDOX) mouse model of osteosarcoma that more closely mimics osteosarcoma in clinical settings. Previous osteosarcoma PDOX models involved implanting a tumor fragment near the femur of nude mice in a space created by separating muscle. Materials and Methods: A hole was created in the tibia of nude mice and an osteosarcoma tumor fragment was implanted directly into the bone. Results: This procedure resulted in tumor growth in the bone similar to osteosarcoma tumors found in clinical patients. Conclusion: The establishment ratio for this procedure is 80% making it a practical and clinically-relevant model for screening effective therapies for osteosarcoma patients.

  • PDOX
  • patient-derived orthotopic xenograft
  • osteosarcoma
  • tibia implantation

Osteosarcoma is a rare type of malignancy that affects mostly children and adolescents. Treatment with a combination of neoadjuvant and adjuvant chemotherapies with surgery improved the prognosis of patients with osteosarcoma (1, 2). However, patients with osteosarcoma often develop chemoresistance, especially patients with metastases, leading to fatality (1-3). Many animal studies using osteosarcoma patient-derived tumors were previously performed to attempt to identify more effective treatments (4-6). However, almost all those studies used a subcutaneous-implantation xenograft model. Subcutaneous-implantation models are poor surrogate models of cancer in clinical patients and may not reflect effectiveness in treatment studies as accurately as orthotopic-implantation models (7). Tumor implantation at the orthotopic site can lead to metastasis, allowing the tumor to mimic the behavior of tumors observed in patients (8). We previously established an osteosarcoma patient-derived orthotopic xenograft (PDOX) mouse model where the tumor is implanted on the femur. The osteosarcoma PDOX model has identified novel treatment strategies (9-15). The present study demonstrates a new implantation procedure for osteosarcoma to the tibia bone to establish a more clinically-relevant PDOX model of this disease.

Materials and Methods

Mice. This study was conducted on athymic nu/nu nude mice (AntiCancer, Inc., San Diego, CA, USA). The procedures followed an AntiCancer, Inc. Institutional Animal Care and Use Committee (IACUC) protocol specifically approved for this study and in accordance with the principles and procedures outlined in the National Institute of Health Guide for the Care and Use of Animals under Assurance Number A3873-1. All animal procedures have been previously described (9-16).

Patient-derived tumor. The osteosarcoma tumor was previously obtained from a 14-year-old boy with pelvic osteosarcoma as part of a UCLA Institutional Review Board approved protocol (IRB#10-001857). Written informed consent was obtained from the patient (16). The patient was not administered chemotherapy or radiotherapy before the fresh biopsy sample was taken (16).

New surgical orthotopic tibia-implantation procedure to establish a more clinically-relevant osteosarcoma PDOX model. Mice containing subcutaneously-implanted tumors larger than 10 mm in diameter were anesthetized with a ketamine mixture and the tumors were harvested and divided into fragments of 1 mm3. An 8 mm incision was made in either the left or right thigh of nude mice (Figure 1A). The mouse leg was bent at the knee to expose the quadriceps and calf through the incision. The medial tibia was then visualized. The membrane was dissected to remove any membrane attachments from the lower-extremity muscle (Figure 1B). Then a 5 mm blade was used to puncture the proximal tibia. Once the tibia was punctured and the blade was 2.5 mm into the bone, the blade was rotated with multiple revolutions to create a hole in the bone (Figure 1C). Fine tweezers were used to smoothen and clean the hole. Once a 1 mm diameter hole was visible, a 1 mm3 tumor fragment was inserted into the hole. Fine tweezers were used to push the tumor fragment into the hole so the tumor was not raised above the bone, preventing it from falling out (Figure 1D). The incision was closed with a 5-0 PDS-II suture. Tumor size was measured with calipers 4, 5, and 6 weeks after tumor implantation. Tumor volume was calculated as described (3). All mice were sacrificed 6 weeks after implantation.

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

Bone-implantation method for osteosarcoma PDOX. (A) An 8 mm incision made on the skin. (B) Quadriceps and calf exposed by bending the knee. The membrane was dissected away from the tibia bone and muscle. Black arrow indicates the knee cap. White arrow indicates the tibia. (C) After a 5-mm blade was used to puncture a hole and was rotated, a 1 mm diameter hole was formed in the tibia. (D) A 1-mm3 tumor fragment was inserted into the hole. Black arrow indicates the implanted tumor fragment.

Hematoxylin and eosin staining. Fixation, paraffin sectioning, and staining were performed as previously described (10). Hematoxylin and eosin (H&E) staining was performed according to standard protocols (15).

Results

Ten mice were implanted using the new procedure. The tumors grew in 8 mice (80%). All tumors were detectable through the skin (Figure 2A and B). No mice had any gait disorder. The tumor volume significantly increased 4, 5, and 6 weeks after tumor implantation (Figure 3). H&E staining showed that tumors comprised viable, highly-dense cancer cells with a pleomorphic spindle shape (Figure 4).

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

Osteosarcoma PDOX growth in the bone. (A) Twenty-eight days after implantation. (B) Forty-two days after implantation.

Figure 3.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 3.

Quantitative osteosarcoma PDOX growth in the bone.

Figure 4.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 4.

Tumor histology of osteosarcoma PDOX in the bone. Scale bars: 100 μm. (A) 100× magnification. (B) 200× magnification.

Discussion

In the present study, we established a new procedure of orthotopic implantation of osteosarcoma in the tibia bone. Compared to the previous surgical orthotopic implantation (SOI) osteosarcoma PDOX model, this new procedure is an improvement because it is a more clinically-accurate tumor model, closely mimicking what is observed in osteosarcoma patients.

The primary difference between the new procedure and the previous one is the location of tumor implantation. Instead of placing the tumor in the space between the muscle and bone, the new procedure implants the tumor directly into the bone, more accurately simulating the growth of osteosarcoma tumors in patients. Because the recess in the tibia was smaller than the space in the muscle, the tumor fragments used in these new procedures were 1 mm3 compared to 3-4 mm3 fragments used previously. However, the tumor cells were very aggressive and grew significantly and quickly in the bone despite the relatively small initial tumor size. The establishment ratio of 80% makes this new procedure practical. Moreover, this procedure is versatile. The method of creating a recess in the bone in which a tumor can be implanted can be applied to implantation into any bone. Many more bone-cancer-implantation PDOX models can be designed from this method.

This PDOX mouse model is useful for two reasons. First, individualized clinically-relevant mouse models can be made for patients with osteosarcoma. With a patient tumor, personal mouse models can assist in determining the most effective treatment plan for a certain patient. Second, previous osteosarcoma PDOX models have already identified potentially more effective treatments (9-16). This improved osteosarcoma PDOX model, which closely resembles clinical osteosarcoma, can be used to test novel therapies. The new procedure for tibia osteosarcoma-tumor implantation described in the present report is important, because with these improved clinically-representative mouse models, treatment experiments can be carried out with better translation to patient therapy and better understanding of the biology of the disease, in contrast to subcutaneous sarcoma mouse models (17).

Acknowledgements

This paper is dedicated to the memory of A. R. Moossa, M.D., Sun Lee, M.D., Professor Li Jiaxi and Masaki Kitajima, MD.

Footnotes

  • Authors’ Contributions

    N.F.W. and J.Y. designed and performed experiments and wrote the paper; R.M.H. gave technical support and conceptual advice. Writing, review, and/or revision of the manuscript: N.F.W., M.B., and R.M.H.

  • This article is freely accessible online.

  • Conflicts of Interest

    N.F.W., J.Y., and RMH are or were unsalaried associates of AntiCancer Inc. which performs contract research with PDOX models. The Authors declare that there are no potential conflicts of interest regarding this study.

  • Funding

    This work was supported in part by a Yokohama City University research grant “KAMOME Project”, and the Robert M. Hoffman Foundation for Cancer Research, both of which had no role in the design, execution, interpretation, or writing of the study.

  • Received November 3, 2020.
  • Revision received November 21, 2020.
  • Accepted November 25, 2020.
  • Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved

References

  1. ↵
    1. Durfee RA,
    2. Mohammed M and
    3. Luu HH
    : Review of osteosarcoma and current management. Rheumatol Ther 3(2): 221-243, 2016. PMID: 27761754. DOI: 10.1007/s40744-016-0046-y
    OpenUrlCrossRefPubMed
  2. ↵
    1. Harrison DJ,
    2. Geller DS,
    3. Gill JD,
    4. Lewis VO and
    5. Gorlick R
    : Current and future therapeutic approaches for osteosarcoma. Expert Rev Anticancer Ther 18(1): 39-50, 2018. PMID: 29210294. DOI: 10.1080/14737140.2018.1413939
    OpenUrlCrossRefPubMed
  3. ↵
    1. Igarashi K,
    2. Kawaguchi K,
    3. Murakami T,
    4. Miyake K,
    5. Kiyuna T,
    6. Miyake M,
    7. Hiroshima Y,
    8. Higuchi T,
    9. Oshiro H,
    10. Nelson SD,
    11. Dry SM,
    12. Li Y,
    13. Yamamoto N,
    14. Hayashi K,
    15. Kimura H,
    16. Miwa S,
    17. Singh SR,
    18. Tsuchiya H and
    19. Hoffman RM
    : Patient-derived orthotopic xenograft models of sarcoma. Cancer Lett 469: 332-339, 2020. PMID: 31639427. DOI: 10.1016/j.canlet.2019.10.028.
    OpenUrlCrossRef
  4. ↵
    1. Nanni P,
    2. Landuzzi L,
    3. Manara MC,
    4. Righi A,
    5. Nicoletti G,
    6. Cristalli C,
    7. Pasello M,
    8. Parra A,
    9. Carrabotta M,
    10. Ferracin M,
    11. Palladini A,
    12. Ianzano ML,
    13. Giusti V,
    14. Ruzzi F,
    15. Magnani M,
    16. Donati DM,
    17. Picci P,
    18. Lollini PL and
    19. Scotlandi K
    : Bone sarcoma patient-derived xenografts are faithful and stable preclinical models for molecular and therapeutic investigations. Sci Rep 9(1): 12174, 2019. PMID: 31434953. DOI: 10.1038/s41598-019-48634-y
    OpenUrlCrossRef
    1. Gill J,
    2. Zhang W,
    3. Zhang Z,
    4. Roth M,
    5. Harrison DJ,
    6. Rowshan S,
    7. Erickson S,
    8. Gatto G,
    9. Kurmasheva R,
    10. Houghton P,
    11. Teicher B,
    12. Smith MA,
    13. Kolb EA and
    14. Gorlick R
    : Dose-response effect of eribulin in preclinical models of osteosarcoma by the pediatric pre-clinical testing consortium. Pediatr Blood Cancer 67(10): e28606, 2020. PMID: 32706456. DOI: 10.1002/pbc.28606
    OpenUrlCrossRef
  5. ↵
    1. Smeester BA,
    2. Slipek NJ,
    3. Pomeroy EJ,
    4. Laoharawee K,
    5. Osum SH,
    6. Larsson AT,
    7. Williams KB,
    8. Stratton N,
    9. Yamamoto K,
    10. Peterson JJ,
    11. Rathe SK,
    12. Mills LJ,
    13. Hudson WA,
    14. Crosby MR,
    15. Wang M,
    16. Rahrmann EP,
    17. Moriarity BS and
    18. Largaespada DA
    : PLX3397 treatment inhibits constitutive CSF1R-induced oncogenic ERK signaling, reduces tumor growth, and metastatic burden in osteosarcoma. Bone 136: 115353, 2020. PMID: 32251854. DOI: 10.1016/j.bone.2020.115353
    OpenUrlCrossRef
  6. ↵
    1. Tran Chau V,
    2. Liu W,
    3. Gerbé de Thoré M,
    4. Meziani L,
    5. Mondini M,
    6. O’Connor MJ,
    7. Deutsch E and
    8. Clémenson C
    : Differential therapeutic effects of PARP and ATR inhibition combined with radiotherapy in the treatment of subcutaneous versus orthotopic lung tumour models. Br J Cancer 123(5): 762-771, 2020. PMID: 32546832. DOI: 10.1038/s41416-020-0931-6
    OpenUrlCrossRef
  7. ↵
    1. Hoffman RM
    : Patient-derived orthotopic xenografts: Better mimic of metastasis than sub-cutaneous xenografts. Nat Rev Cancer 15(8): 451-452, 2015. PMID: 26422835. DOI: 10.1038/nrc3972
    OpenUrlCrossRefPubMed
  8. ↵
    1. Higuchi T,
    2. Oshiro H,
    3. Miyake K,
    4. Sugisawa N,
    5. Han Q,
    6. Tan Y,
    7. Park J,
    8. Zhang Z,
    9. Razmjooei S,
    10. Yamamoto N,
    11. Hayashi K,
    12. Kimura H,
    13. Miwa S,
    14. Igarashi K,
    15. Bouvet M,
    16. Chawla SP,
    17. Singh SR,
    18. Tsuchiya H and
    19. Hoffman RM
    : Oral recombinant methioninase, combined with oral caffeine and injected cisplatinum, overcome cisplatinum-resistance and regresses patient-derived orthotopic xenograft model of osteosarcoma. Anticancer Res 39(9): 4653-4657, 2019. PMID: 31519563. DOI: 10.21873/anticanres.13646
    OpenUrlAbstract/FREE Full Text
  9. ↵
    1. Higuchi T,
    2. Sugisawa N,
    3. Miyake K,
    4. Oshiro H,
    5. Yamamoto N,
    6. Hayashi K,
    7. Kimura H,
    8. Miwa S,
    9. Igarashi K,
    10. Bouvet M,
    11. Singh SR,
    12. Tsuchiya H and
    13. Hoffman RM
    : The combination of olaratumab with doxorubicin and cisplatinum regresses a chemotherapy-resistant osteosarcoma in a patient-derived orthotopic xenograft mouse model. Transl Oncol 12(9): 1257-1263, 2019. PMID: 31299622. DOI: 10.1016/j.tranon.2019.06.002
    OpenUrlCrossRef
    1. Higuchi T,
    2. Sugisawa N,
    3. Miyake K,
    4. Oshiro H,
    5. Yamamoto N,
    6. Hayashi K,
    7. Kimura H,
    8. Miwa S,
    9. Igarashi K,
    10. Chawla SP,
    11. Bouvet M,
    12. Singh SR,
    13. Tsuchiya H and
    14. Hoffman RM
    : Sorafenib and palbociclib combination regresses a cisplatinum-resistant osteosarcoma in a PDOX mouse model. Anticancer Res 39(8): 4079-4084, 2019. PMID: 31366491. DOI: 10.21873/anticanres.13565
    OpenUrlAbstract/FREE Full Text
    1. Higuchi T,
    2. Sugisawa N,
    3. Miyake K,
    4. Oshiro H,
    5. Yamamoto N,
    6. Hayashi K,
    7. Kimura H,
    8. Miwa S,
    9. Igarashi K,
    10. Kline Z,
    11. Belt P,
    12. Chawla SP,
    13. Bouvet M,
    14. Singh SR,
    15. Tsuchiya H and
    16. Hoffman RM
    : Combination treatment with sorafenib and everolimus regresses a doxorubicin-resistant osteosarcoma in a PDOX mouse model. Anticancer Res 39(9): 4781-4786, 2019. PMID: 31519579. DOI: 10.21873/anticanres.13662
    OpenUrlAbstract/FREE Full Text
    1. Higuchi T,
    2. Sugisawa N,
    3. Miyake K,
    4. Oshiro H,
    5. Yamamoto N,
    6. Hayashi K,
    7. Kimura H,
    8. Miwa S,
    9. Igarashi K,
    10. Kline Z,
    11. Bouvet M,
    12. Singh SR,
    13. Tsuchiya H and
    14. Hoffman RM
    : Pioglitazone, an agonist of PPARγ, reverses doxorubicin-resistance in an osteosarcoma patient-derived orthotopic xenograft model by downregulating P-glycoprotein expression. Biomed Pharmacother 118: 109356, 2019. PMID: 31545293. DOI: 10.1016/j.biopha.2019.109356
    OpenUrlCrossRef
    1. Higuchi T,
    2. Sugisawa N,
    3. Yamamoto J,
    4. Oshiro H,
    5. Han Q,
    6. Yamamoto N,
    7. Hayashi K,
    8. Ki-mura H,
    9. Miwa S,
    10. Igarashi K,
    11. Tan Y,
    12. Kuchipudi S,
    13. Bouvet M,
    14. Singh SR,
    15. Tsuchiya H and
    16. Hoffman RM
    : The combination of oral-recombinant methioninase and azacitidine arrests a chemotherapy-resistant osteosarcoma patient-derived orthotopic xenograft mouse model. Cancer Chemother Pharmacol 85(2): 285-291, 2020. PMID: 31705268. DOI: 10.1007/s00280-019-03986-0
    OpenUrlCrossRef
  10. ↵
    1. Higuchi T,
    2. Yamamoto J,
    3. Sugisawa N,
    4. Tashiro Y,
    5. Nishino H,
    6. Yamamoto N,
    7. Hayashi K,
    8. Kimura H,
    9. Miwa S,
    10. Igarashi K,
    11. Bouvet M,
    12. Singh SR,
    13. Tsuchiya H and
    14. Hoffman RM
    : PPARγ agonist pioglitazone in combination with cisplatinum arrests a chemotherapy-resistant osteosarcoma PDOX model. Cancer Genomics Proteomics 17(1): 35-40, 2020. PMID: 31882549.
    OpenUrlAbstract/FREE Full Text
  11. ↵
    1. Higuchi T,
    2. Miyake K,
    3. Oshiro H,
    4. Sugisawa N,
    5. Yamamoto N,
    6. Hayashi K,
    7. Kimura H,
    8. Miwa S,
    9. Igarashi K,
    10. Chawla SP,
    11. Bouvet M,
    12. Singh SR,
    13. Tsuchiya H and
    14. Hoffman RM
    : Trabectedin and irinotecan combination regresses a cisplatinum-resistant osteosarcoma in a patient-derived orthotopic xenograft nude-mouse model. Biochem Biophys Res Commun 513(2): 326-331, 2019. PMID: 30955860. DOI: 10.1016/j.bbrc.2019.03.191
    OpenUrlCrossRef
  12. ↵
    1. Marchetto A,
    2. Ohmura S,
    3. Orth MF,
    4. Knott MML,
    5. Colombo MV,
    6. Arrigoni C,
    7. Bardinet V,
    8. Saucier D,
    9. Wehweck FS,
    10. Li J,
    11. Stein S,
    12. Gerke JS,
    13. Baldauf MC,
    14. Musa J,
    15. Dallmayer M,
    16. Romero-Pérez L,
    17. Hölting TLB,
    18. Amatruda JF,
    19. Cossarizza A,
    20. Henssen AG,
    21. Kirchner T,
    22. Moretti M,
    23. Cidre-Aranaz F,
    24. Sannino G and
    25. Grünewald TGP
    : Oncogenic hijacking of a developmental transcription factor evokes vulnerability toward oxidative stress in Ewing sarcoma. Nat Commun 11(1): 2423, 2020. PMID: 32415069. DOI: 10.1038/s41467-020-16244-2
    OpenUrlCrossRef
View Abstract
PreviousNext
Back to top

In this issue

In Vivo: 35 (1)
In Vivo
Vol. 35, Issue 1
January-February 2021
  • 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 In Vivo.

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.
A Novel Procedure for Orthotopic Tibia Implantation for Establishment of a More Clinical Osteosarcoma PDOX Mouse Model
(Your Name) has sent you a message from In Vivo
(Your Name) thought you would like to see the In Vivo web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
1 + 1 =
Solve this simple math problem and enter the result. E.g. for 1+3, enter 4.
Citation Tools
A Novel Procedure for Orthotopic Tibia Implantation for Establishment of a More Clinical Osteosarcoma PDOX Mouse Model
NATHANIEL F. WU, JUN YAMAMOTO, MICHAEL BOUVET, ROBERT M. HOFFMAN
In Vivo Jan 2021, 35 (1) 105-109; DOI: 10.21873/invivo.12237

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Reprints and Permissions
Share
A Novel Procedure for Orthotopic Tibia Implantation for Establishment of a More Clinical Osteosarcoma PDOX Mouse Model
NATHANIEL F. WU, JUN YAMAMOTO, MICHAEL BOUVET, ROBERT M. HOFFMAN
In Vivo Jan 2021, 35 (1) 105-109; DOI: 10.21873/invivo.12237
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

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

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

  • Drug Screening of Potential Multiple Target Inhibitors for Estrogen Receptor-α-positive Breast Cancer
  • Combination Cancer Therapy of a Del1 Fragment and Cisplatin Enhanced Therapeutic Efficiency In Vivo
  • TBX15 rs98422, DNM3 rs1011731, RAD51B rs8017304, and rs2588809 Gene Polymorphisms and Associations With Pituitary Adenoma
Show more Experimental Studies

Similar Articles

Keywords

  • PDOX
  • patient-derived orthotopic xenograft
  • osteosarcoma
  • tibia implantation
In Vivo

© 2021 In Vivo

Powered by HighWire