| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Experimental Therapeutics, Preclinical Pharmacology |
Pediatric Surgical Research Laboratories [A. E. S., L. A. P., B. P. C., P. K. D., D. T. M.], and Laboratory for Tissue Engineering and Organ Fabrication [J. P. V.], Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts 02114
Purpose: Müllerian inhibiting substance (MIS) causes Müllerianduct regression in mammalian, avian, and reptilian embryos; MIS also inhibits growth in vitro of Müllerian-derived cell lines and primary cells from human ovarian carcinomas. We hypothesize that highly purified MIS delivered parenterally inhibits ovarian cancer in vivo.
Experimental Design: To test the efficacy of highly purified MIS against ovarian cancer cell lines in vivo, we treated immunosuppressed mice with MIS after implanting OVCAR 8 or IGROV 1 human ovarian cancer cells beneath the renal capsules and measured tumor volume over time. Animals were treated with daily injections of 10 µg of purified exogenous recombinant human MIS or by endogenous MIS secreted from cells growing on biodegradable mesh.
Results: The average graft size ratio (change in size compared with starting size) of the OVCAR 8 tumor implants was larger in the control animals than in animals treated for 2 weeks (P < 0.019) or 3 weeks (P < 0.001) with parenteral MIS, or after treating with MIS produced from transfected cells, which impregnated the biodegradable mesh (P = 0.02). The average graft size ratio of the IGROV 1 tumors was also larger in the control animals than in those treated with injected MIS (P = 0.0174).
Conclusions: Highly purified recombinant human MIS, delivered parenterally, or MIS produced endogenously causes inhibition of human ovarian cancer cell lines in vivo, providing convincing preclinical evidence to support the use of MIS as a parenteral agent for the treatment of ovarian cancer.
This article has been cited by other articles:
|
|
 |
|
  S. Zhang, C. Balch, M. W. Chan, H.-C. Lai, D. Matei, J. M. Schilder, P. S. Yan, T. H-M. Huang, and K. P. Nephew Identification and Characterization of Ovarian Cancer-Initiating Cells from Primary Human Tumors Cancer Res., June 1, 2008; 68(11): 4311 - 4320. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. C. Rodriguez, B.J. Rimel, W. Watkin, J. M. Turbov, C. Barry, H. Du, G. L. Maxwell, and J.M. Cline Progestin Treatment Induces Apoptosis and Modulates Transforming Growth Factor-{beta} in the Uterine Endometrium Cancer Epidemiol. Biomarkers Prev., March 1, 2008; 17(3): 578 - 584. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Renlund, R. Pieretti-Vanmarcke, F. H. O'Neill, L. Zhang, P. K. Donahoe, and J. Teixeira c-Jun N-terminal Kinase Inhibitor II (SP600125) Activates Mullerian Inhibiting Substance Type II Receptor-Mediated Signal Transduction Endocrinology, January 1, 2008; 149(1): 108 - 115. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Marca and A. Volpe The Anti-Mullerian hormone and ovarian cancer Hum. Reprod. Update, May 1, 2007; 13(3): 265 - 273. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Pieretti-Vanmarcke, P. K. Donahoe, L. A. Pearsall, D. M. Dinulescu, D. C. Connolly, E. F. Halpern, M. V. Seiden, and D. T. MacLaughlin Mullerian Inhibiting Substance enhances subclinical doses of chemotherapeutic agents to inhibit human and mouse ovarian cancer PNAS, November 14, 2006; 103(46): 17426 - 17431. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q.-a. Yuan, H. H. Simmons, M. K. Robinson, M. Russeva, W. A. Marasco, and G. P. Adams Development of engineered antibodies specific for the Mullerian inhibiting substance type II receptor: a promising candidate for targeted therapy of ovarian cancer. Mol. Cancer Ther., August 1, 2006; 5(8): 2096 - 2105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Pieretti-Vanmarcke, P. K. Donahoe, P. Szotek, T. Manganaro, M. K. Lorenzen, J. Lorenzen, D. C. Connolly, E. F. Halpern, and D. T. MacLaughlin Recombinant Human Mullerian Inhibiting Substance Inhibits Long-term Growth of MIS Type II Receptor-Directed Transgenic Mouse Ovarian Cancers In vivo Clin. Cancer Res., March 1, 2006; 12(5): 1593 - 1598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Gupta, J. L. Carey, H. Kawakubo, A. Muzikansky, J. E. Green, P. K. Donahoe, D. T. MacLaughlin, and S. Maheswaran Mullerian inhibiting substance suppresses tumor growth in the C3(1)T antigen transgenic mouse mammary carcinoma model PNAS, March 1, 2005; 102(9): 3219 - 3224. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Renaud, D. T. MacLaughlin, E. Oliva, B. R. Rueda, and P. K. Donahoe Endometrial cancer is a receptor-mediated target for Mullerian Inhibiting Substance PNAS, January 4, 2005; 102(1): 111 - 116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. U. Barbie, D. A. Barbie, D. T. MacLaughlin, S. Maheswaran, and P. K. Donahoe Mullerian Inhibiting Substance inhibits cervical cancer cell growth via a pathway involving p130 and p107 PNAS, December 23, 2003; 100(26): 15601 - 15606. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
