Skip to main content

Main menu

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

Salmonella typhimurium A1-R Exquisitely Targets and Arrests a Matrix-producing Triple-negative Breast Carcinoma in a PDOX Model

KAZUYUKI HAMADA, YUSUKE AOKI, JUN YAMAMOTO, CHIHIRO HOZUMI, MING ZHAO, TAKUYA MURATA, NORIHIKO SUGISAWA, MICHAEL BOUVET, TAKUYA TSUNODA and ROBERT M. HOFFMAN
In Vivo November 2021, 35 (6) 3067-3071; DOI: https://doi.org/10.21873/invivo.12602
KAZUYUKI HAMADA
1AntiCancer Inc, San Diego, CA, U.S.A.;
2Department of Surgery, University of California, San Diego, CA, U.S.A.;
3Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
YUSUKE AOKI
1AntiCancer Inc, San Diego, CA, U.S.A.;
2Department 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
JUN YAMAMOTO
1AntiCancer Inc, San Diego, CA, U.S.A.;
2Department 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
CHIHIRO HOZUMI
4AntiCancer Japan Inc, Narita, Japan;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
MING ZHAO
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
TAKUYA MURATA
5Department of Obstetrics and Gynecology 2, Kawasaki Medical School, Okayama, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
NORIHIKO SUGISAWA
1AntiCancer Inc, San Diego, CA, U.S.A.;
2Department 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
2Department 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
TAKUYA TSUNODA
3Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: all@anticancer.com ttsunoda@med.showa-u.ac.jp
ROBERT M. HOFFMAN
1AntiCancer Inc, San Diego, CA, U.S.A.;
2Department 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 ttsunoda@med.showa-u.ac.jp
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Background/Aim: Triple-negative matrix-producing breast carcinoma (MPBC) is rare, recalcitrant, and highly aggressive. The present study aimed to determine the efficacy of tumor-targeting leucine-arginine auxotroph Salmonella typhimurium (S. typhimurium) A1-R on a triple-negative MPBC in a patient-derived orthotopic xenograft (PDOX) model. Materials and Methods: The PDOX MPBC model was established in the left second mammary gland of nude mice by surgical orthotopic implantation (SOI). PDOX models were randomized into two groups when the tumor volume reached over 70 mm3: a control group (n=6); and a tumor-targeting S. typhimurium A1-R group (n=7), [intravenous (i.v.) injection of S. typhimurium A1-R via the tail vein, weekly, for two weeks]. All mice were sacrificed on day 14. Tumor volume and body weight were measured once per week. Results: S. typhimurium A1-R exquisitely targeted and arrested the growth of the MPBC PDOX compared to the control group (p=0.017). Conclusion: S. typhimurium A1-R has future clinical potential for triple-negative MPBC patients.

  • PDOX
  • patient-derived orthotopic xenograft
  • triple-negative breast cancer
  • matrix-producing breast carcinoma
  • Salmonella typhimurium A1-R
  • tumor targeting
  • efficacy

Triple-negative matrix-producing breast carcinoma (MPBC) is defined by the absence of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) and the production of a cartilaginous or osseous matrix (1, 2). Effective therapy for triple-negative MPBC has not been established due to its rarity (3).

Our laboratory pioneered the patient-derived orthotopic xenograft (PDOX) model 30 years ago by establishing the technique of surgical orthotopic implantation (SOI) (4, 5). We have shown that the PDOX model retains the histopathological/molecular and metastatic characteristics of the original tumor after SOI unlike the subcutaneous PDX mouse model (5-7). We previously showed eribulin regressed triple-negative MPBC in PDOX mouse models (8, 9).

Leucine-arginine auxotroph Salmonella typhimurium (S. typhimurium) A1-R, expressing green fluorescent protein (GFP), accurately targets tumors and does not grow well in normal tissue due to its leucine–arginine auxotrophy (10-12). S. typhimurium A1-R inhibited prostate (10, 12), breast (11, 13, 14), lung (15, 16), pancreatic (17-19), ovarian (20, 21), stomach (22), and cervical cancer (23), as well as sarcoma (24-26), melanoma (27), and glioma (28).

In the present report we demonstrate that S. typhimurium A1-R exquisitely targets and arrests a triple-negative MPBC in a PDOX mouse model.

Materials and Methods

Mouse studies. Ethical approval was obtained from the ethics committee of the AntiCancer Institutional Animal Care and Use Committee under the National Institutes of Health Guide Assurance Number A3873-1(8). All experiments were conducted in compliance with Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines 2.0.

Patient tumor. The patient tumor was provided as a discarded pathology specimen by Kawasaki Medical School, Japan, following Research Ethics Committee of Kawasaki Medical School and Hospital approval. All experiments were carried out in accordance with the Declaration of Helsinki and regulations for human studies, and informed consent was obtained from the patient. The patient MPBC tumor was previously established to grow subcutaneously in nude mice. Subcutaneously-grown tumor was harvested and minced into 3 mm3 fragments and orthotopically implanted into the 2nd left mammary gland of nude mice as previously described (8).

Preparation of Salmonella typhimurium A1-R. S. typhimurium A1-R-GFP (AntiCancer, Inc., San Diego, CA, USA) was produced as described in our previous publications (10-28): Bacteria were incubated in Luria-Bertani (LB) medium containing ampicillin at 37°C overnight with shaking. The bacteria were then diluted 10-fold in LB medium containing ampicillin and incubated for 3 hours under the same conditions. Bacteria were washed with phosphate-buffered saline (PBS), suspended in PBS, and injected into nude mice via the tail vein.

Treatment protocol for the triple-negative MPBC PDOX model. The detailed experimental schema is shown in Figure 1. The triple-negative MPBC PDOX models were randomized into two groups when the tumor volume was over 70 mm3: Control: untreated control mice; A1-R: S. typhimurium A1-R-GFP treated mice [i.v., 5×107 colony-forming units (CFU) S. typhimurium A1-R -GFP in 100 μl PBS (weekly, two weeks)]. Each group comprised six and seven mice, respectively. Tumor size and body weight were measured once a week. Tumor volume was calculated using the following formula: tumor volume (mm)=length (mm) × width (mm) × width (mm) × 1/2. All mice were sacrificed on day 14.

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

Experimental schema. S. typhimurium A1-R-GFP was injected into the tail vein of triple-negative matrix-producing breast carcinoma PDOX nude mice [5×107 colony-forming units (CFU) per 100 μl of PBS].

Fluorescence imaging of S. typhimurium A1-R-GFP in the triple-negative MPBC PDOX. Fluorescence images were obtained and analyzed using the UVP ChemStudio (Analytik Jena, Thuringia, Germany).

Statistical analysis. GraphPad Prism 8.4.3 (GraphPad Software, Inc., San Diego, CA, USA) was used for statistical calculations. The Student’s t-test was used to compare groups. Data are the mean values±SD. p≤0.05 is defined as statistically significant.

Results

Exquisite targeting of the triple-negative MPBC PDOX by S. typhimurium A1-R-GFP. Twenty-four hours after infection of triple-negative MPBC PDOX with S. typhimurium A1-R -GFP, the bacteria selectively targeted the tumor, as demonstrated by GFP fluorescence in the tumor but not in the liver or spleen of the triple-negative MPBC PDOX mouse model (Figure 2).

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

Tumor targeting by S. typhimurium A1-R-GFP. Selective tumor targeting of S. typhimurium A1-R-GFP to the triple-negative matrix-producing breast carcinoma (MPBC) PDOX. Imaging was performed with the UVP ChemStudio (Analytik, Jena, Germany). Representative images are shown.

Efficacy of S. typhimurium A1-R ‐ GFP on the triple-negative MPBC PDOX. S. typhimurium A1-R arrested the growth of the triple-negative MPBC (p=0.017). The final tumor volume was obtained on treatment-day 14. Average tumor volume of the control group was 205±70 mm3 and in the S. typhimurium A1-R -GFP group 112±37 mm3 (Figure 3).

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

Efficacy of S. typhimurium A1-R-GFP on the triple-negative matrix-producing breast carcinoma (MPBC) PDOX nude mice. Tumors were measured at the indicated time points after the initiation of treatment. Control group (n=6) vs. S. typhimurium A1-R-GFP-treated group (n=7). Line graphs show the tumor volume at the indicated time points. Error bars represent the mean±SD.

No effect of S. typhimurium A1-R-GFP on body weight of the triple-negative MPBC PDOX mouse model. To determine whether S. typhimurium A1-GFP had a gross adverse effect, the mouse body weight was measured at pre-treatment and post-treatment. The final body weight on treatment-day 14 was 24.7±0.9 g for the control group and 24.1±3.1 g for the S. typhimurium A1-R ‐ GFP group. There were no significant differences in the body weight between the two groups on day14 (p=0.73) (Figure 4), which suggests that S. typhimurium A1-R-GFP had no obvious side effects.

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

Effect of S. typhimurium A1-R-GFP on mouse body weight in each group. Bar graphs show the bodyweight of mice at the indicated time points. No significant body weight differences were observed between the groups at each point. Control group (n=6) vs., S. typhimurium A1-R-GFP-treated group (n=7), on day 0, on day 14, p=0.53, 0.73, respectively.

Discussion

In the present study, S. typhimurium A1-R-GFP accurately targeted the triple-negative MPBC in a PDOX model and arrested its growth.

Kusafuka et al. reported the frequency of MPBCs is only 0.2% of all breast cancers (2). MPBC is usually triple-negative breast cancer (TNBC) and has a high proliferative activity, indicated by high histological grade, high Ki-67 index, and high level of p53 expression (1, 29). Shimada et al. reported that the mean Ki-67 index of non-TNBC MPBCs (45%) was higher than that of TNBCs (36%) (3).

Due to its rarity, there are only a few clinical trials for MPBC and they showed poor efficacy (3, 30, 31). Therefore, novel effective therapy is urgently needed for MPBC patients. Our previous studies of triple-negative MPBC and common triple-negative breast cancer (TNBC) PDOX mouse models showed eribulin was effective (8, 9).

Bacterial therapy has gained popularity as a cancer immunotherapy in recent years (32). Salmonella, Clostridium, and other bacterial genera have been shown to control tumor growth and promote survival in animal models (32). S. typhimurium A1-R is an auxotrophic leucine-arginine facultative-anaerobic S. typhimurium strain, which selectively targets and proliferates in tumors of all types due to, at least in part, its nutritional needs, which appear to be satisfied in the rich nutritional milieu of tumors, but it is severely restricted in normal tissue (12). Thus S. typhimurium A1-R can directly target tumors as well as serve as an anti-tumor immuno-stimulator. In a previous study, we showed that S. typhimurium A1-R enabled CD-8 T-cells to penetrate tumors (33). In the present study, S. typhimurium A1-R-GFP primarily localized and proliferated in the triple-negative MPBC tumor and S. typhimurium A1-R-GFP was undetectable in the liver and spleen. These results suggest the clinical potential of S. typhimurium A1-R for triple-negative MPBC.

Conclusion

S. typhimurium A1-R-GFP exquisitely targeted and arrested the growth of a triple-negative MPBC in a PDOX mouse model without apparent toxicity. The triple-negative MPBC PDOX model allows the development of precise, individualized, improved therapy for patients with this recalcitrant disease.

Acknowledgements

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

Footnotes

  • This article is freely accessible online.

  • Authors’ Contributions

    K.H. and R.M.H designed and performed experiments, analyzed data, and wrote the article; T.M. provided the tumor specimen; C.H. established the patient tumor specimens in nude mice; J.Y., Z.M., N.S., Y.A., and M.B. provided technical support and conceptual advice.: K.H., T.T., and R.M.H. wrote, reviewed, and/or revised the manuscript.

  • Conflicts of Interest

    AntiCancer Inc. uses PDOX models for contract research. K.H., Y.A., M.Z., N.S., and R.M.H. are or were unsalaried associates of AntiCancer Inc. C.H. is an unsalaried associate of AntiCancer Japan. The Authors declare no competing financial interests.

  • Funding

    The present study was funded in part by The Robert M Hoffman Foundation For Cancer Research which had no other role in the study.

  • Received August 1, 2021.
  • Revision received August 23, 2021.
  • Accepted August 24, 2021.
  • Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved

References

  1. ↵
    1. Gibson GR,
    2. Qian D,
    3. Ku JK and
    4. Lai LL
    : Metaplastic breast cancer: clinical features and outcomes. Am Surg 71(9): 725-730, 2005. PMID: 16468506.
    OpenUrlCrossRefPubMed
  2. ↵
    1. Kusafuka K,
    2. Muramatsu K,
    3. Kasami M,
    4. Kuriki K,
    5. Hirobe K,
    6. Hayashi I,
    7. Watanabe H,
    8. Hiraki Y,
    9. Shukunami C,
    10. Mochizuki T and
    11. Kameya T
    : Cartilaginous features in matrix-producing carcinoma of the breast: four cases report with histochemical and immunohistochemical analysis of matrix molecules. Mod Pathol 21(10): 1282-1292, 2008. PMID: 18622387. DOI: 10.1038/modpathol.2008.120
    OpenUrlCrossRefPubMed
  3. ↵
    1. Shimada K,
    2. Ishikawa T,
    3. Yamada A,
    4. Sugae S,
    5. Narui K,
    6. Shimizu D,
    7. Chishima T and
    8. Endo I
    : Matrix-producing carcinoma as an aggressive triple-negative breast cancer: Clinicopathological features and response to neoadjuvant chemotherapy. Anticancer Res 39(7): 3863-3869, 2019. PMID: 31262914. DOI: 10.21873/anticanres.13536
    OpenUrlAbstract/FREE Full Text
  4. ↵
    1. Fu XY,
    2. Besterman JM,
    3. Monosov A and
    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(20): 9345-9349, 1991. PMID: 1924398. DOI: 10.1073/pnas.88.20.9345
    OpenUrlAbstract/FREE Full Text
  5. ↵
    1. Hoffman RM
    : Patient-derived orthotopic xenografts: better mimic of metastasis than subcutaneous xenografts. Nat Rev Cancer 15(8): 451-452, 2015. PMID: 26422835. DOI: 10.1038/nrc3972
    OpenUrlCrossRefPubMed
    1. Furukawa T,
    2. Kubota T,
    3. Watanabe M,
    4. Kitajima M and
    5. Hoffman RM
    : Orthotopic transplantation of histologically intact clinical specimens of stomach cancer to nude mice: correlation of metastatic sites in mouse and individual patient donors. Int J Cancer 53(4): 608-612, 1993. PMID: 8436434. DOI: 10.1002/ijc.2910530414
    OpenUrlCrossRefPubMed
  6. ↵
    1. Hoffman RM
    : Orthotopic metastatic mouse models for anticancer drug discovery and evaluation: a bridge to the clinic. Invest New Drugs 17(4): 343-359, 1999. PMID: 10759402. DOI: 10.1023/a:1006326203858
    OpenUrlCrossRefPubMed
  7. ↵
    1. Yamamoto J,
    2. Murata T,
    3. Tashiro Y,
    4. Higuchi T,
    5. Sugisawa N,
    6. Nishino H,
    7. Inubushi S,
    8. Sun YU,
    9. Lim H,
    10. Miyake K,
    11. Hongo A,
    12. Nomura T,
    13. Saitoh W,
    14. Moriya T,
    15. Tanino H,
    16. Hozumi C,
    17. Bouvet M,
    18. Singh SR,
    19. Endo I and
    20. Hoffman RM
    : A triple-negative matrix-producing breast carcinoma patient-derived orthotopic xenograft (PDOX) mouse model is sensitive to bevacizumab and vinorelbine, regressed by eribulin and resistant to olaparib. Anticancer Res 40(5): 2509-2514, 2020. PMID: 32366395. DOI: 10.21873/anticanres.14221
    OpenUrlAbstract/FREE Full Text
  8. ↵
    1. Lim HI,
    2. Yamamoto J,
    3. Inubushi S,
    4. Nishino H,
    5. Tashiro Y,
    6. Sugisawa N,
    7. Han Q,
    8. Sun YU,
    9. Choi HJ,
    10. Nam SJ,
    11. Kim MB,
    12. Lee JS,
    13. Hozumi C,
    14. Bouvet M,
    15. Singh SR and
    16. Hoffman RM
    : A single low dose of eribulin regressed a highly aggressive triple-negative breast cancer in a patient-derived orthotopic xenograft model. Anticancer Res 40(5): 2481-2485, 2020. PMID: 32366392. DOI: 10.21873/anticanres.14218
    OpenUrlAbstract/FREE Full Text
  9. ↵
    1. Zhao M,
    2. Yang M,
    3. Li XM,
    4. Jiang P,
    5. Baranov E,
    6. Li S,
    7. Xu M,
    8. Penman S and
    9. Hoffman RM
    : Tumor-targeting bacterial therapy with amino acid auxotrophs of GFP-expressing Salmonella typhimurium. Proc Natl Acad Sci USA 102(3): 755-760, 2005. PMID: 15644448. DOI: 10.1073/pnas.0408422102
    OpenUrlAbstract/FREE Full Text
  10. ↵
    1. Zhao M,
    2. Yang M,
    3. Ma H,
    4. Li X,
    5. Tan X,
    6. Li S,
    7. Yang Z and
    8. Hoffman RM
    : Targeted therapy with a Salmonella typhimurium leucine-arginine auxotroph cures orthotopic human breast tumors in nude mice. Cancer Res 66(15): 7647-7652, 2006. PMID: 16885365. DOI: 10.1158/0008-5472.CAN-06-0716
    OpenUrlAbstract/FREE Full Text
  11. ↵
    1. Zhao M,
    2. Geller J,
    3. Ma H,
    4. Yang M,
    5. Penman S and
    6. Hoffman RM
    : Monotherapy with a tumor-targeting mutant of Salmonella typhimurium cures orthotopic metastatic mouse models of human prostate cancer. Proc Natl Acad Sci USA 104(24): 10170-10174, 2007. PMID: 17548809. DOI: 10.1073/pnas.0703867104
    OpenUrlAbstract/FREE Full Text
  12. ↵
    1. Zhang Y,
    2. Tome Y,
    3. Suetsugu A,
    4. Zhang L,
    5. Zhang N,
    6. Hoffman RM and
    7. Zhao M
    : Determination of the optimal route of administration of Salmonella typhimurium A1-R to target breast cancer in nude mice. Anticancer Res 32(7): 2501-2508, 2012. PMID: 22753706.
    OpenUrlAbstract/FREE Full Text
  13. ↵
    1. Zhang Y,
    2. Miwa S,
    3. Zhang N,
    4. Hoffman RM and
    5. Zhao M
    : Tumor-targeting Salmonella typhimurium A1-R arrests growth of breast-cancer brain metastasis. Oncotarget 6(5): 2615-2622, 2015. PMID: 25575815. DOI: 10.18632/oncotarget.2811
    OpenUrlCrossRefPubMed
  14. ↵
    1. Uchugonova A,
    2. Zhao M,
    3. Zhang Y,
    4. Weinigel M,
    5. König K and
    6. Hoffman RM
    : Cancer-cell killing by engineered Salmonella imaged by multiphoton tomography in live mice. Anticancer Res 32(10): 4331-4337, 2012. PMID: 23060555.
    OpenUrlAbstract/FREE Full Text
  15. ↵
    1. Liu F,
    2. Zhang L,
    3. Hoffman RM and
    4. Zhao M
    : Vessel destruction by tumor-targeting Salmonella typhimurium A1-R is enhanced by high tumor vascularity. Cell Cycle 9(22): 4518-4524, 2010. PMID: 21135579. DOI: 10.4161/cc.9.22.13744
    OpenUrlCrossRefPubMed
  16. ↵
    1. Nagakura C,
    2. Hayashi K,
    3. Zhao M,
    4. Yamauchi K,
    5. Yamamoto N,
    6. Tsuchiya H,
    7. Tomita K,
    8. Bouvet M and
    9. Hoffman RM
    : Efficacy of a genetically-modified Salmonella typhimurium in an orthotopic human pancreatic cancer in nude mice. Anticancer Res 29(6): 1873-1878, 2009. PMID: 19528442.
    OpenUrlAbstract/FREE Full Text
    1. Yam C,
    2. Zhao M,
    3. Hayashi K,
    4. Ma H,
    5. Kishimoto H,
    6. McElroy M,
    7. Bouvet M and
    8. Hoffman RM
    : Monotherapy with a tumor-targeting mutant of S. typhimurium inhibits liver metastasis in a mouse model of pancreatic cancer. J Surg Res 164(2): 248-255, 2010. PMID: 19766244. DOI: 10.1016/j.jss.2009.02.023
    OpenUrlCrossRefPubMed
  17. ↵
    1. Hiroshima Y,
    2. Zhao M,
    3. Zhang Y,
    4. Maawy A,
    5. Hassanein MK,
    6. Uehara F,
    7. Miwa S,
    8. Yano S,
    9. Momiyama M,
    10. Suetsugu A,
    11. Chishima T,
    12. Tanaka K,
    13. Bouvet M,
    14. Endo I and
    15. Hoffman RM
    : Comparison of efficacy of Salmonella typhimurium A1-R and chemotherapy on stem-like and non-stem human pancreatic cancer cells. Cell Cycle 12(17): 2774-2780, 2013. PMID: 23966167. DOI: 10.4161/cc.25872
    OpenUrlCrossRefPubMed
  18. ↵
    1. Matsumoto Y,
    2. Miwa S,
    3. Zhang Y,
    4. Hiroshima Y,
    5. Yano S,
    6. Uehara F,
    7. Yamamoto M,
    8. Toneri M,
    9. Bouvet M,
    10. Matsubara H,
    11. Hoffman RM and
    12. Zhao M
    : Efficacy of tumor-targeting Salmonella typhimurium A1-R on nude mouse models of metastatic and disseminated human ovarian cancer. J Cell Biochem 115(11): 1996-2003, 2014. PMID: 24924355. DOI: 10.1002/jcb.24871
    OpenUrlCrossRefPubMed
  19. ↵
    1. Matsumoto Y,
    2. Miwa S,
    3. Zhang Y,
    4. Zhao M,
    5. Yano S,
    6. Uehara F,
    7. Yamamoto M,
    8. Hiroshima Y,
    9. Toneri M,
    10. Bouvet M,
    11. Matsubara H,
    12. Tsuchiya H and
    13. Hoffman RM
    : Intraperitoneal administration of tumor-targeting Salmonella typhimurium A1-R inhibits disseminated human ovarian cancer and extends survival in nude mice. Oncotarget 6(13): 11369-11377, 2015. PMID: 25957417. DOI: 10.18632/oncotarget.3607
    OpenUrlCrossRefPubMed
  20. ↵
    1. Yano S,
    2. Zhang Y,
    3. Zhao M,
    4. Hiroshima Y,
    5. Miwa S,
    6. Uehara F,
    7. Kishimoto H,
    8. Tazawa H,
    9. Bouvet M,
    10. Fujiwara T and
    11. Hoffman RM
    : Tumor-targeting Salmonella typhimurium A1-R decoys quiescent cancer cells to cycle as visualized by FUCCI imaging and become sensitive to chemotherapy. Cell Cycle 13(24): 3958-3963, 2014. PMID: 25483077. DOI: 10.4161/15384101.2014.964115
    OpenUrlCrossRefPubMed
  21. ↵
    1. Hiroshima Y,
    2. Zhang Y,
    3. Zhao M,
    4. Zhang N,
    5. Murakami T,
    6. Maawy A,
    7. Mii S,
    8. Uehara F,
    9. Yamamoto M,
    10. Miwa S,
    11. Yano S,
    12. Momiyama M,
    13. Mori R,
    14. Matsuyama R,
    15. Chishima T,
    16. Tanaka K,
    17. Ichikawa Y,
    18. Bouvet M,
    19. Endo I and
    20. Hoffman RM
    : Tumor-targeting Salmonella typhimurium A1-R in combination with trastuzumab eradicates HER-2-positive cervical cancer cells in patient-derived mouse models. PLoS One 10(6): e0120358, 2015. PMID: 26047477. DOI: 10.1371/journal.pone.0120358
    OpenUrlCrossRefPubMed
  22. ↵
    1. Murakami T,
    2. DeLong J,
    3. Eilber FC,
    4. Zhao M,
    5. Zhang Y,
    6. Zhang N,
    7. Singh A,
    8. Russell T,
    9. Deng S,
    10. Reynoso J,
    11. Quan C,
    12. Hiroshima Y,
    13. Matsuyama R,
    14. Chishima T,
    15. Tanaka K,
    16. Bouvet M,
    17. Chawla S,
    18. Endo I and
    19. Hoffman RM
    : Tumor-targeting Salmonella typhimurium A1-R in combination with doxorubicin eradicate soft tissue sarcoma in a patient-derived orthotopic xenograft (PDOX) model. Oncotarget 7(11): 12783-12790, 2016. PMID: 26859573. DOI: 10.18632/oncotarget.7226
    OpenUrlCrossRefPubMed
    1. Hiroshima Y,
    2. Zhao M,
    3. Zhang Y,
    4. Zhang N,
    5. Maawy A,
    6. Murakami T,
    7. Mii S,
    8. Uehara F,
    9. Yamamoto M,
    10. Miwa S,
    11. Yano S,
    12. Momiyama M,
    13. Mori R,
    14. Matsuyama R,
    15. Chishima T,
    16. Tanaka K,
    17. Ichikawa Y,
    18. Bouvet M,
    19. Endo I and
    20. Hoffman RM
    : Tumor-targeting Salmonella typhimurium A1-R arrests a chemo-resistant patient soft-tissue sarcoma in nude mice. PLoS One 10(8): e0134324, 2015. PMID: 26237416. DOI: 10.1371/journal.pone.0134324
    OpenUrlCrossRefPubMed
  23. ↵
    1. Kiyuna T,
    2. Murakami T,
    3. Tome Y,
    4. Kawaguchi K,
    5. Igarashi K,
    6. Zhang Y,
    7. Zhao M,
    8. Li Y,
    9. Bouvet M,
    10. Kanaya F,
    11. Singh A,
    12. Dry S,
    13. Eilber FC and
    14. Hoffman RM
    : High efficacy of tumor-targeting Salmonella typhimurium A1-R on a doxorubicin- and dactolisib-resistant follicular dendritic-cell sarcoma in a patient-derived orthotopic xenograft PDOX nude mouse model. Oncotarget 7(22): 33046-33054, 2016. PMID: 27105519. DOI: 10.18632/oncotarget.8848
    OpenUrlCrossRefPubMed
  24. ↵
    1. Yamamoto M,
    2. Zhao M,
    3. Hiroshima Y,
    4. Zhang Y,
    5. Shurell E,
    6. Eilber FC,
    7. Bouvet M,
    8. Noda M and
    9. Hoffman RM
    : Efficacy of tumor-targeting Salmonella A1-R on a melanoma patient-derived orthotopic xenograft (PDOX) nude-mouse model. PLoS One 11(8): e0160882, 2016. PMID: 27500926. DOI: 10.1371/journal.pone.0160882
    OpenUrlCrossRefPubMed
  25. ↵
    1. Momiyama M,
    2. Zhao M,
    3. Kimura H,
    4. Tran B,
    5. Chishima T,
    6. Bouvet M,
    7. Endo I and
    8. Hoffman RM
    : Inhibition and eradication of human glioma with tumor-targeting Salmonella typhimurium in an orthotopic nude-mouse model. Cell Cycle 11(3): 628-632, 2012. PMID: 22274398. DOI: 10.4161/cc.11.3.19116
    OpenUrlCrossRefPubMed
  26. ↵
    1. Wargotz ES and
    2. Norris HJ
    : Metaplastic carcinomas of the breast. I. Matrix-producing carcinoma. Hum Pathol 20(7): 628-635, 1989. PMID: 2544506. DOI: 10.1016/0046-8177(89)90149-4
    OpenUrlCrossRefPubMed
  27. ↵
    1. Al Sayed AD,
    2. El Weshi AN,
    3. Tulbah AM,
    4. Rahal MM and
    5. Ezzat AA
    : Metaplastic carcinoma of the breast clinical presentation, treatment results and prognostic factors. Acta Oncol 45(2): 188-195, 2006. PMID: 16546865. DOI: 10.1080/02841860500513235
    OpenUrlCrossRefPubMed
  28. ↵
    1. Hennessy BT,
    2. Giordano S,
    3. Broglio K,
    4. Duan Z,
    5. Trent J,
    6. Buchholz TA,
    7. Babiera G,
    8. Hortobagyi GN and
    9. Valero V
    : Biphasic metaplastic sarcomatoid carcinoma of the breast. Ann Oncol 17(4): 605-613, 2006. PMID: 16469754. DOI: 10.1093/annonc/mdl006
    OpenUrlCrossRefPubMed
  29. ↵
    1. Forbes NS,
    2. Coffin RS,
    3. Deng L,
    4. Evgin L,
    5. Fiering S,
    6. Giacalone M,
    7. Gravekamp C,
    8. Gulley JL,
    9. Gunn H,
    10. Hoffman RM,
    11. Kaur B,
    12. Liu K,
    13. Lyerly HK,
    14. Marciscano AE,
    15. Moradian E,
    16. Ruppel S,
    17. Saltzman DA,
    18. Tattersall PJ,
    19. Thorne S,
    20. Vile RG,
    21. Zhang HH,
    22. Zhou S and
    23. McFadden G
    : White paper on microbial anti-cancer therapy and prevention. J Immunother Cancer 6(1): 78, 2018. PMID: 30081947. DOI: 10.1186/s40425-018-0381-3
    OpenUrlAbstract/FREE Full Text
  30. ↵
    1. Murakami T,
    2. Hiroshima Y,
    3. Zhang Y,
    4. Zhao M,
    5. Kiyuna T,
    6. Hwang HK,
    7. Miyake K,
    8. Homma Y,
    9. Mori R,
    10. Matsuyama R,
    11. Chishima T,
    12. Ichikawa Y,
    13. Tanaka K,
    14. Bouvet M,
    15. Endo I and
    16. Hoffman RM
    : Tumor-targeting Salmonella typhimurium A1-R promotes tumoricidal CD8+ T cell tumor infiltration and arrests growth and metastasis in a syngeneic pancreatic-cancer orthotopic mouse model. J Cell Biochem 119(1): 634-639, 2018. PMID: 28628234. DOI: 10.1002/jcb.26224
    OpenUrlCrossRefPubMed
PreviousNext
Back to top

In this issue

In Vivo: 35 (6)
In Vivo
Vol. 35, Issue 6
November-December 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.
Salmonella typhimurium A1-R Exquisitely Targets and Arrests a Matrix-producing Triple-negative Breast Carcinoma in a PDOX 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.
3 + 1 =
Solve this simple math problem and enter the result. E.g. for 1+3, enter 4.
Citation Tools
Salmonella typhimurium A1-R Exquisitely Targets and Arrests a Matrix-producing Triple-negative Breast Carcinoma in a PDOX Model
KAZUYUKI HAMADA, YUSUKE AOKI, JUN YAMAMOTO, CHIHIRO HOZUMI, MING ZHAO, TAKUYA MURATA, NORIHIKO SUGISAWA, MICHAEL BOUVET, TAKUYA TSUNODA, ROBERT M. HOFFMAN
In Vivo Nov 2021, 35 (6) 3067-3071; DOI: 10.21873/invivo.12602

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Reprints and Permissions
Share
Salmonella typhimurium A1-R Exquisitely Targets and Arrests a Matrix-producing Triple-negative Breast Carcinoma in a PDOX Model
KAZUYUKI HAMADA, YUSUKE AOKI, JUN YAMAMOTO, CHIHIRO HOZUMI, MING ZHAO, TAKUYA MURATA, NORIHIKO SUGISAWA, MICHAEL BOUVET, TAKUYA TSUNODA, ROBERT M. HOFFMAN
In Vivo Nov 2021, 35 (6) 3067-3071; DOI: 10.21873/invivo.12602
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
    • Conclusion
    • 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

  • Systemic Administration of Lipopolysaccharide from Porphyromonas gingivalis Decreases Neprilysin Expression in the Mouse Hippocampus
  • Monitoring T-Cell Kinetics in the Early Recovery Period of Lung Transplantation Cases by Copy Number Levels of T-Cell Receptor Excision Circle
  • Successful Surgical Outcome of Feline Inductive Odontogenic Tumor in Three Cats
Show more Experimental Studies

Similar Articles

Keywords

  • PDOX
  • patient-derived orthotopic xenograft
  • triple-negative breast cancer
  • matrix-producing breast carcinoma
  • Salmonella typhimurium A1-R
  • tumor targeting
  • efficacy
In Vivo

© 2023 In Vivo

Powered by HighWire