Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
December-2017 Volume 14 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
December-2017 Volume 14 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Prevention of body weight loss and sarcopenia by a novel selective androgen receptor modulator in cancer cachexia models

  • Authors:
    • Megumi Morimoto
    • Katsuji Aikawa
    • Takahito Hara
    • Masuo Yamaoka
  • View Affiliations / Copyright

    Affiliations: Oncology Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa 251‑8555, Japan, Integrated Technology Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa 251‑8555, Japan
  • Pages: 8066-8071
    |
    Published online on: October 17, 2017
       https://doi.org/10.3892/ol.2017.7200
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Cancer cachexia is a syndrome that impairs the quality of life and overall survival of patients, and thus the effectiveness of anticancer agents. There are no effective therapies for cancer cachexia due to the complexity of the syndrome, and insufficient knowledge of its pathogenesis results in difficulty establishing appropriate animal models. Previously, promising results have been obtained in clinical trials using novel agents including the ghrelin receptor agonist anamorelin, and the selective androgen receptor modulator (SARM) enobosarm to treat cachexia in patients with cancer. The present study examined the pharmacological effects of SARM‑2f, a novel non‑steroidal small molecule SARM, in animal models. SARM‑2f increased body and skeletal muscle weight without significantly increasing the weight of the seminal vesicles or prostates of the castrated male rats. In the mice with tumor necrosis factor α‑induced cachexia, SARM‑2f and TP restored body weight, carcass weight, and food consumption rate. In the C26 and G361 cancer cachexia animal models, body and carcass weight, lean body mass, and the weight of the levator ani muscle were increased by SARM‑2f and TP treatments. Tissue selectivity of SARM‑2f was also observed in these animal models. The results demonstrate the anabolic effects of SARM‑2f in a cytokine‑induced cachexia model and other cancer cachexia models, and suggest that SARM‑2f may be a novel therapeutic option for cachexia in patients with cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, Jatoi A, Loprinzi C, MacDonald N, Mantovani G, et al: Definition and classification of cancer cachexia: An international consensus. Lancet Oncol. 12:489–495. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Argilés JM, Busquets S, Stemmler B and López-Soriano FJ: Cancer cachexia: Understanding the molecular basis. Nat Rev Cancer. 14:754–762. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Fearon KC, Glass DJ and Guttridge DC: Cancer cachexia: Mediators, signaling, and metabolic pathways. Cell Metab. 16:153–166. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Cooper C, Burden ST, Cheng H and Molassiotis A: Understanding and managing cancer-related weight loss and anorexia: Insights from a systematic review of qualitative research. J Cachexia Sarcopenia Muscle. 6:99–111. 2015. View Article : Google Scholar : PubMed/NCBI

5 

Tuca A, Jimenez-Fonseca P and Gascón P: Clinical evaluation and optimal management of cancer cachexia. Crit Rev Oncol Hematol. 88:625–636. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Porporato PE: Understanding cachexia as a cancer metabolism syndrome. Oncogenesis. 5:e2002016. View Article : Google Scholar : PubMed/NCBI

7 

Coss CC, Bohl CE and Dalton JT: Cancer cachexia therapy: A key weapon in the fight against cancer. Curr Opin Clin Nutr Metab Care. 14:268–273. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Dodson S, Baracos VE, Jatoi A, Evans WJ, Cella D, Dalton JT and Steiner MS: Muscle wasting in cancer cachexia: Clinical implications, diagnosis, and emerging treatment strategies. Annu Rev Med. 62:265–279. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Madeddu C, Mantovani G, Gramignano G and Macciò A: Advances in pharmacologic strategies for cancer cachexia. Expert Opin Pharmacother. 16:2163–2177. 2015. View Article : Google Scholar : PubMed/NCBI

10 

Molfino A, Amabile MI, Fanelli Rossi F and Muscaritoli M: Novel therapeutic options for cachexia and sarcopenia. Expert Opin Biol Ther. 16:1239–1244. 2016. View Article : Google Scholar : PubMed/NCBI

11 

Strasser F, Palmer JL, Schover LR, Yusuf SW, Pisters K, Vassilopoulou-Sellin R, DeGracia B, Willey JS and Bruera E: The impact of hypogonadism and autonomic dysfunction on fatigue, emotional function, and sexual desire in male patients with advanced cancer: A pilot study. Cancer. 107:2949–2957. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Burney BO, Hayes TG, Smiechowska J, Cardwell G, Papusha V, Bhargava P, Konda B, Auchus RJ and Garcia JM: Low testosterone levels and increased inflammatory markers in patients with cancer and relationship with cachexia. J Clin Endocrinol Metab. 97:E700–E709. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, Eder R, Tennstedt S, Ulloor J, Zhang A, et al: Adverse events associated with testosterone administration. N Engl J Med. 363:109–122. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Vigen R, O'Donnell CI, Barón AE, Grunwald GK, Maddox TM, Bradley SM, Barqawi A, Woning G, Wierman ME, Plomondon ME, et al: Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 10:1829–1836. 2013. View Article : Google Scholar

15 

Aikawa K, Miyawaki T, Hitaka T, Imai YN, Hara T, Miyazaki J, Yamaoka M, Kusaka M, Kanzaki N, Tasaka A, et al: Synthesis and biological evaluation of novel selective androgen receptor modulators (SARMs). Part I. Bioorg Med Chem. 23:2568–2578. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Dwarkasing JT, Boekschoten MV, Argilès JM, van Dijk M, Busquets S, Penna F, Toledo M, Laviano A, Witkamp RF and van Norren K: Differences in food intake of tumor-bearing cachectic mice are associated with hypothalamic serotonin signaling. J Cachexia Sarcopenia Muscle. 6:84–94. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Ballarò R, Costelli P and Penna F: Animal models for cancer cachexia. Curr Opin Support Palliat Care. 10:281–287. 2016. View Article : Google Scholar : PubMed/NCBI

18 

Talbert EE, Metzger GA, He WA and Guttridge DC: Modeling human cancer cachexia in colon 26 tumor-bearing adult mice. J Cachexia Sarcopenia Muscle. 5:321–328. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Ustünel I, Akkoyunlu G and Demir R: The effect of testosterone on gastrocnemius muscle fibres in growing and adult male and female rats: A histochemical, morphometric and ultrastructural study. Anat Histol Embryol. 32:70–79. 2003. View Article : Google Scholar : PubMed/NCBI

20 

Urban RJ: Growth hormone and testosterone: Anabolic effects on muscle. Horm Res Paediatr. 76 Suppl 1:S81–S83. 2011. View Article : Google Scholar

21 

De Gendt K and Verhoeven G: Tissue- and cell-specific functions of the androgen receptor revealed through conditional knockout models in mice. Mol Cell Endocrinol. 352:13–25. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Aikawa K, Asano M, Ono K, Habuka N, Yano J, Wilson K, Fujita H, Kandori H, Hara T, Morimoto M, et al: Synthesis and biological evaluation of novel selective androgen receptor modulators (SARMs) Part III: Discovery of 4-(5-oxopyrrolidine-1-yl)benzonitrile derivative 2f as a clinical candidate. Bioorg Med Che. 25:3330–3349.. 2017. View Article : Google Scholar

23 

Argiles JM, Lopez-Soriano FJ and Busquets S: Counteracting inflammation: A promising therapy in cachexia. Crit Rev Oncog. 17:253–262. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Thompson RW, McClung JM, Baltgalvis KA, Davis JM and Carson JA: Modulation of overload-induced inflammation by aging and anabolic steroid administration. Exp Gerontol. 41:1136–1148. 2006. View Article : Google Scholar : PubMed/NCBI

25 

Srinath R and Dobs A: Enobosarm (GTx-024, S-22): A potential treatment for cachexia. Future Oncol. 10:187–194. 2014. View Article : Google Scholar : PubMed/NCBI

26 

Dillon EL, Basra G, Horstman AM, Casperson SL, Randolph KM, Durham WJ, Urban RJ, Diaz-Arrastia C, Levine L, Hatch SS, et al: Cancer cachexia and anabolic interventions: A case report. J Cachexia Sarcopenia Muscle. 3:253–263. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Del Fabbro E, Garcia JM, Dev R, Hui D, Williams J, Engineer D, Palmer JL, Schover L and Bruera E: Testosterone replacement for fatigue in hypogonadal ambulatory males with advanced cancer: A preliminary double-blind placebo-controlled trial. Support Care Cancer. 21:2599–2607. 2013. View Article : Google Scholar : PubMed/NCBI

28 

de Vooqt HJ, Smith PH, Pavone-Macaluso M, de Pauw M and Suciu S: Cardiovascular side effects of diethylstilbestrol, cyproterone acetate, medroxyprogesterone acetate and estramustine phosphate used for the treatment of advanced prostatic cancer: Results from European Organization for Research on Treatment of Cancer Trials 30761 and 30762. J Urol. 135:303–307. 1986. View Article : Google Scholar : PubMed/NCBI

29 

Ponnusamy S, Sullivan RD, Thiyagarajan T, Tillmann H, Getzenberg RH and Narayanan R: Tissue selective androgen receptor modulators (SARMs) increase pelvic floor muscle mass in ovariectomized mice. J Cell Biochem. 118:640–646. 2017. View Article : Google Scholar : PubMed/NCBI

30 

Chisamore MJ, Gentile MA, Dillon GM, Baran M, Gambone C, Riley S, Schmidt A, Flores O, Wilkinson H and Alves SE: A novel selective androgen receptor modulator (SARM) MK-4541 exerts anti-androgenic activity in the prostate cancer xenograft R-3327G and anabolic activity on skeletal muscle mass & function in castrated mice. J Steroid Biochem Mol Biol. 163:88–97. 2016. View Article : Google Scholar : PubMed/NCBI

31 

Blanqué R, Lepescheux L, Auberval M, Minet D, Merciris D, Cottereaux C, Clément-Lacroix P, Delerive P and Namour F: Characterization of GLPG0492, a selective androgen receptor modulator, in a mouse model of hindlimb immobilization. BMC Musculoslelet Disord. 15:2912014. View Article : Google Scholar

32 

Akita K, Harada K, Ichihara J, Takata N, Takahashi Y and Saito K: A novel selective androgen receptor modulator, NEP28, is efficacious in muscle and brain without serious side effects on prostate. Eur J Pharmacol. 720:107–114. 2013. View Article : Google Scholar : PubMed/NCBI

33 

Zhang X, Allan GF, Tannenbaum P, Sbriscia T, Linton O, Lai MT, Haynes-Johnson D, Bhattacharjee S, Lundeen SG and Sui Z: Pharmacological characterization of an imidazolopyrazole as novel selective androgen receptor modulator. J Steroid Biochem Mol Biol. 134:51–58. 2013. View Article : Google Scholar : PubMed/NCBI

34 

Narayanan R, Mohler ML, Bohl CE, Miller DD and Dalton JT: Selective androgen receptor modulators in preclinical and clinical development. Nucl Recept Signal. 6:e0102008.PubMed/NCBI

35 

Narayanan R, Coss CC, Yepuru M, Kearbey JD, Miller DD and Dalton JT: Steroidal androgens and nonsteroidal, tissue-selective androgen receptor modulator, S-22, regulate androgen receptor function through distinct genomic and nongenomic signaling pathways. Mol Endocrinol. 22:2448–2465. 2008. View Article : Google Scholar : PubMed/NCBI

36 

Crawford J, Prado CM, Johnston MA, Gralla RJ, Taylor RP, Hancock ML and Dalton JT: Study design and rationale for phase 3 clinical development program of enobosarm, a selective androgen receptor modulator, for the prevention and treatment of muscle wasting in cancer patients (POWER Trials). Curr Oncol Rep. 18:372016. View Article : Google Scholar : PubMed/NCBI

37 

Garber K: No longer going to waste. Nat Biotechnol. 34:458–461. 2016. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Morimoto M, Aikawa K, Hara T and Yamaoka M: Prevention of body weight loss and sarcopenia by a novel selective androgen receptor modulator in cancer cachexia models. Oncol Lett 14: 8066-8071, 2017.
APA
Morimoto, M., Aikawa, K., Hara, T., & Yamaoka, M. (2017). Prevention of body weight loss and sarcopenia by a novel selective androgen receptor modulator in cancer cachexia models. Oncology Letters, 14, 8066-8071. https://doi.org/10.3892/ol.2017.7200
MLA
Morimoto, M., Aikawa, K., Hara, T., Yamaoka, M."Prevention of body weight loss and sarcopenia by a novel selective androgen receptor modulator in cancer cachexia models". Oncology Letters 14.6 (2017): 8066-8071.
Chicago
Morimoto, M., Aikawa, K., Hara, T., Yamaoka, M."Prevention of body weight loss and sarcopenia by a novel selective androgen receptor modulator in cancer cachexia models". Oncology Letters 14, no. 6 (2017): 8066-8071. https://doi.org/10.3892/ol.2017.7200
Copy and paste a formatted citation
x
Spandidos Publications style
Morimoto M, Aikawa K, Hara T and Yamaoka M: Prevention of body weight loss and sarcopenia by a novel selective androgen receptor modulator in cancer cachexia models. Oncol Lett 14: 8066-8071, 2017.
APA
Morimoto, M., Aikawa, K., Hara, T., & Yamaoka, M. (2017). Prevention of body weight loss and sarcopenia by a novel selective androgen receptor modulator in cancer cachexia models. Oncology Letters, 14, 8066-8071. https://doi.org/10.3892/ol.2017.7200
MLA
Morimoto, M., Aikawa, K., Hara, T., Yamaoka, M."Prevention of body weight loss and sarcopenia by a novel selective androgen receptor modulator in cancer cachexia models". Oncology Letters 14.6 (2017): 8066-8071.
Chicago
Morimoto, M., Aikawa, K., Hara, T., Yamaoka, M."Prevention of body weight loss and sarcopenia by a novel selective androgen receptor modulator in cancer cachexia models". Oncology Letters 14, no. 6 (2017): 8066-8071. https://doi.org/10.3892/ol.2017.7200
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team