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Mullerian inhibiting substance

Pauline Estupina, Alexandre Fontayne, Jean-Marc Barret, Nathalie Kersual, Olivier Dubreuil, Marion Le Blay, Alexandre Pichard, Marta Jarlier, Martine Pugnière, Maëva Chauvin, Thierry Chardès, Jean-Pierre Pouget, Emmanuel Deshayes, Alexis Rossignol, Toufik Abache, Christophe de Romeuf, Aurélie Terrier, Lucie Verhaeghe, Christine Gaucher, Jean-François Prost, André Pèlegrin, Isabelle Navarro-Teulon
Ovarian cancer is the leading cause of death in women with gynecological cancers and despite recent advances, new and more efficient therapies are crucially needed. Müllerian Inhibiting Substance type II Receptor (MISRII, also named AMHRII) is expressed in most ovarian cancer subtypes and is a novel potential target for ovarian cancer immunotherapy. We previously developed and tested 12G4, the first murine monoclonal antibody (MAb) against human MISRII. Here, we report the humanization, affinity maturation and glyco-engineering steps of 12G4 to generate the Fc-optimized 3C23K MAb, and the evaluation of its in vivo anti-tumor activity...
February 24, 2017: Oncotarget
Sang Ho Park, Youn Jee Chung, Jae Yen Song, Sang Il Kim, David Pépin, David T MacLaughlin, Patricia K Donahoe, Jang Heub Kim
Müllerian inhibiting substance/anti-Müllerian hormone (MIS/AMH) has been suggested as a biotherapeutic agent in gynecological cancers that highly express the MIS/AMH type II receptors (MISRII/AMHRII) but the anticancer mechanisms by which MIS/AMH acts are not fully understood. Our experiments show that MIS/AMH inhibits ovarian cancer by deregulating the Wnt signal pathway via the β-catenin interacting protein (ICAT). MIS/AMH inhibition of ICAT by small interfering RNAs (siRNA) decreased ICAT driven ovarian cancer cell viability as measured by the methylthiazoltetrazolium assay, reversed cell cycle arrest and annexin V expression and diminished migration by scratch wound assay...
March 2017: International Journal of Oncology
Motohiro Kano, Amanda E Sosulski, LiHua Zhang, Hatice D Saatcioglu, Dan Wang, Nicholas Nagykery, Mary E Sabatini, Guangping Gao, Patricia K Donahoe, David Pépin
The ovarian reserve represents the stock of quiescent primordial follicles in the ovary which is gradually depleted during a woman's reproductive lifespan, resulting in menopause. Müllerian inhibiting substance (MIS) (or anti-Müllerian hormone/AMH), which is produced by granulosa cells of growing follicles, has been proposed as a negative regulator of primordial follicle activation. Here we show that long-term parenteral administration of superphysiological doses of MIS, using either an adeno-associated virus serotype 9 (AAV9) gene therapy vector or recombinant protein, resulted in a complete arrest of folliculogenesis in mice...
February 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
T Fréour, P Barrière, D Masson
BACKGROUND: Long-term consequences of cancer treatments in young women, and especially fertility issues, are gaining attention as survival rates increase. Breast cancer is the most frequent malignancy in women of reproductive age. AIM: The purpose of this review is to describe serum anti-müllerian hormone (AMH) level at diagnosis and its evolution during and after chemotherapy in women of reproductive age treated for breast cancer. Second, the impact of taxanes on AMH, the association between AMH and amenorrhea, and the comparison of AMH with other hormonal markers of ovarian reserve were studied...
January 27, 2017: European Journal of Cancer
Yu-Chi Li, Man-Ling Luo, Huan Guo, Tian-Tian Wang, Shou-Ren Lin, Jian-Bo Chen, Qian Ma, Yan-Li Gu, Zhi-Mao Jiang, Yao-Ting Gui
Nuclear receptor subfamily 0 group B member 1 (Nr0b1) is an atypical member of the nuclear receptor family that is predominantly expressed in mouse Sertoli cells (SCs). Mutations of NR0B1 in humans cause adrenal failure and hypogonadotropic hypogonadism. The targeted mutagenesis of Nr0b1 in mice has revealed a primary gonadal defect characterized by the overexpression of aromatase and cellular obstruction of the seminiferous tubules and efferent ductules, leading to germ cell death and infertility. The transgenic expression of Nr0b1 under the control of the Müllerian-inhibiting substance promoter (MIS-Nr0b1), which is selectively expressed in SCs, improves fertility...
September 2016: International Journal of Molecular Medicine
David Kurz
Undescended testes (UDTs) are a relatively common finding in newborn males, especially in those born prematurely. Upon discovering a non-intrascrotal testis, it is important to determine whether the testis is palpable or non-palpable and whether the finding is unilateral or bilateral. Imaging should not be used in this workup, as no current modality has been shown to be adequately sensitive or specific to aid in management decisions. Patients with UDTs diagnosed after 6 months of age should be referred to a specialist for correction so that surgery may be performed within 1 year thereafter...
March 2016: Current Treatment Options in Pediatrics
Eric B Rondeau, Cassandra V Laurie, Stewart C Johnson, Ben F Koop
BACKGROUND: Anti-Müllerian hormone (amh) or Müllerian-inhibiting substance (mis) is a member of the transforming growth factor-β family of hormones. This gene plays a key role in vertebrate male sex-determination by inhibiting the development of the Müllerian ducts, and has been shown to be the master sex-determinant in the Patagonian pejerrey. RESULTS: In the lingcod, Ophiodon elongatus, both males and females share one copy of amh, however we have identified a second duplicate copy that appears solely in the male individuals...
April 22, 2016: BMC Research Notes
Xiaozhen Liu, Shaoping Nie, Qiang Yu, Xiaoyin Wang, Danfei Huang, Mingyong Xie
Nonylphenols (NPs) are considered as important environmental toxicants and potential endocrine disrupting compounds which can disrupt male reproductive system. 4-[1-Ethyl-1-methylhexy] phenol (4-NP65 ) is one of the main isomers of technical nonylphenol mixtures. In the present study, effect of NPs was evaluated from an isomer-specific viewpoint using 4-NP65 . Decreased mRNA expression levels of estrogen receptor (ER)-α, ER-β, androgen receptor (AR) and progesterone receptor (PR) were observed in the cells exposed to 4-NP65 for 24 h...
February 2017: Environmental Toxicology
Jyoti Bala, Shashi Seth, Rakesh Dhankhar, Veena Singh Ghalaut
INTRODUCTION: Anti-Mullerian Hormone (AMH) is a glycoprotein of the transforming growth factor-β (TGF-β) family that seems to reflect the continuous non-cyclical growth of small follicles and can be considered an indirect index of the size of the resting primordial follicle pool. Accordingly, AMH represents a marker of Ovarian Reserve (OR) and is particularly useful in demonstrating ovarian tissue damage induced by chemotherapy. AIM: To evaluate and compare the levels of AMH in Breast Carcinoma patients before and after chemotherapy with age matched healthy controls and to assess whether AMH as a biochemical marker of the OR might improve prediction of chemotherapy related outcomes in these patients...
February 2016: Journal of Clinical and Diagnostic Research: JCDR
E Basal, T Ayeni, Q Zhang, C Langstraat, P K Donahoe, D Pepin, X Yin, E Leof, W Cliby
The MIS pathway is a potential therapeutic target in epithelial ovarian cancer (EOC): signaling requires both type II (T2R) and type I receptors (T1R), and results in growth inhibition. MISR2 is expressed in EOC, but the prevalence and relative contributions of candidate T1R remain unknown. We sought to: a) determine expression of T1R in EOC; b) assess impact of T1R expression with clinical outcomes; c) verify MIS-dependent Smad signaling and growth inhibition in primary EOC cell cultures. Tissue microarrays (TMA) were developed for analysis of T1Rs (ALK2/3/6) and MISR2 expression...
2016: Current Molecular Medicine
Yeon Soo Jung, Hee Jung Kim, Seok Kyo Seo, Young Sik Choi, Eun Ji Nam, Sunghoon Kim, Sang Wun Kim, Hyuck Dong Han, Jae Wook Kim, Young Tae Kim
PURPOSE: This study aimed to investigate whether Müllerian inhibiting substance (MIS) in combination with calcitriol modulates proliferation and apoptosis of human ovarian cancer (OCa) cell lines (SKOV3, OVCAR3, and OVCA433) and identify the signaling pathway by which MIS mediates apoptosis. MATERIALS AND METHODS: OCa cell lines were treated with MIS in the absence or presence of calcitriol. Cell viability and proliferation were evaluated using the Cell Counting Kit-8 assay and apoptosis was evaluated by DNA fragmentation assay...
January 2016: Yonsei Medical Journal
Ying Liu, Hai-Yun Yen, Theresa Austria, Jonas Pettersson, Janos Peti-Peterdi, Robert Maxson, Martin Widschwendter, Louis Dubeau
Predisposition to breast and extrauterine Müllerian carcinomas in BRCA1 mutation carriers is due to a combination of cell-autonomous consequences of BRCA1 inactivation on cell cycle homeostasis superimposed on cell-nonautonomous hormonal factors magnified by the effects of BRCA1 mutations on hormonal changes associated with the menstrual cycle. We used the Müllerian inhibiting substance type 2 receptor (Mis2r) promoter and a truncated form of the Follicle stimulating hormone receptor (Fshr) promoter to introduce conditional knockouts of Brca1 and p53 not only in mouse mammary and Müllerian epithelia, but also in organs that control the estrous cycle...
October 2015: EBioMedicine
Deepanshu Joshi, Shio Kumar Singh
Orexin A (OXA), a hypothalamic neuropeptide, and its receptor (OX1R) are primarily expressed in lateral hypothalamus and are involved in the control of various biological functions. Expressions of OXA and OX1R have also been reported in peripheral organs like gastrointestinal and genital tracts. In the present study, expressions of OXA and OX1R have been observed in the testis of Parkes strain neonatal mice by semi-quantitative RT-PCR and western blot analyses. Immunohistochemical study also revealed their presence on spermatogonia, Sertoli cells and in the interstitium of the testis...
December 1, 2016: General and Comparative Endocrinology
Nassim Arouche, Jean-Yves Picard, Danielle Monniaux, Soazik P Jamin, Bernard Vigier, Nathalie Josso, Richard L Cate, Nathalie di Clemente, Joëlle Taieb
Plasma anti-Müllerian hormone (AMH) concentrations have been recently found to be predictive of the number of embryos recovered after FSH superovulatory treatment in the cow. However, the sensitivity of the Active Müllerian-inhibiting substance/AMH ELISA (ref. 10-14400; DSL-Beckman-Coulter) used to make these measurements in bovine plasma samples is low because it was developed to measure human AMH levels. To overcome this limitation, we developed an immunoassay specific for the bovine (B), ovine (O), and caprine (C) species, the bovine-ovine-caprine (BOC) ELISA...
November 2015: Theriogenology
David Pépin, Amanda Sosulski, Lihua Zhang, Dan Wang, Vinod Vathipadiekal, Katherine Hendren, Caroline M Coletti, Aaron Yu, Cesar M Castro, Michael J Birrer, Guangping Gao, Patricia K Donahoe
To improve ovarian cancer patient survival, effective treatments addressing chemoresistant recurrences are particularly needed. Mullerian inhibiting substance (MIS) has been shown to inhibit the growth of a stem-like population of ovarian cancer cells. We have recently engineered peptide modifications to human MIS [albumin leader Q425R MIS (LRMIS)] that increase production and potency in vitro and in vivo. To test this novel therapeutic peptide, serous malignant ascites from highly resistant recurrent ovarian cancer patients were isolated and amplified to create low-passage primary cell lines...
August 11, 2015: Proceedings of the National Academy of Sciences of the United States of America
F Nemati, J-M Barret, G Massonnet, H Bougherara, A Nicolas, E Martel, E Donnadieu, J Prost, D Decaudin
BACKGROUND: Müllerian inhibiting substance, also called anti-Müllerian hormone (AMH), belongs to the TGF-alpha family and plays a key role during sexual development. Various reports have underlined expression of AMHRII in human gynecologic cancers including ovarian cancers (OC). Based on these considerations, a humanized glyco-engineered monoclonal antibody (3C23K) specific to AMHRII has been developed. In this study, we have assessed AMHRII expression in a panel of OC patient-derived xenografts (PDXs) and evaluated in vivo efficacy of 3C23K...
March 2015: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Youn Jee Chung, Hyun Jung Kim, Sang Ho Park, Joo Hee Yoon, Mee Ran Kim, Suk Woo Nam, David T MacLaughlin, Patricia K Donahoe, Jang Heub Kim
Müllerian inhibiting substance (MIS) has been shown to inhibit growth of a number of tumors in vitro and/or in vivo, but the downstream pathways which it regulates are not fully understood. In the present study we show that MIS type II receptor was highly expressed in AN3CA cells, a cell line derived from human endometrial cancer cell in which MIS-treatment caused a reduction of cell viability, and induced cellular apoptosis and genes involved cell cycle arrest. To understand the genome-wide effects of MIS on gene regulation, we performed serial gene expression analyses from 0 to 96 h at 24 h intervals after treating AN3CA cells with MIS...
May 2015: International Journal of Oncology
Nathalie Kersual, Véronique Garambois, Thierry Chardès, Jean-Pierre Pouget, Imed Salhi, Caroline Bascoul-Mollevi, Frédéric Bibeau, Muriel Busson, Henri Vié, Béatrice Clémenceau, Christian K Behrens, Pauline Estupina, André Pèlegrin, Isabelle Navarro-Teulon
Ovarian cancer has the highest mortality rate among gynecologic malignancies. The monoclonal antibody 12G4 specifically recognizes the human Müllerian inhibiting substance type II receptor (MISRII) that is strongly expressed in human granulosa cell tumors (GCT) and in the majority of human epithelial ovarian cancers (EOC). To determine whether MISRII represents an attractive target for antibody-based tumor therapy, we first confirmed by immunohistochemistry with 12G4 its expression in all tested GCT samples (4/4) and all, but one, EOC human tissue specimens (13/14)...
2014: MAbs
Jang Heub Kim, David T MacLaughlin, Patricia K Donahoe
Müllerian inhibiting substance (MIS), also called anti-Müllerian hormone (AMH), is a member of the transforming growth factor-β super-family of growth and differentiation response modifiers. It is produced in immature Sertoli cells in male embryos and binds to MIS/AMH receptors in primordial Müllerian ducts to cause regression of female reproductive structures that are the precursors to the fallopian tubes, the surface epithelium of the ovaries, the uterus, the cervix, and the upper third of the vagina...
September 2014: Obstetrics & Gynecology Science
Leili Safdarian, Zahra Khayatzadeh, Ebrahim Djavadi, Atossa Mahdavi, Marzieh Aghahosseini, Ashraf Aleyasin, Parvin Fallahi, Sima Khayatzadeh, Arash Ahmadzadeh, Mohhamad Bagher Larijani
BACKGROUND: Detection of best predictor of ovarian reserve in patients with temporarily or consistently elevated early follicular phase serum levels of FSH is one of the most important goals in assisted reproductive technique (ART). OBJECTIVE: To evaluate whether high level of anti-mullerian hormone level is related to success of ART in patients with temporarily or consistently elevated early follicular phase serum levels of FSH. MATERIALS AND METHODS: Sixty three women underwent intracytoplasmic sperm injection (ICSI) with GnRH-agonist long protocol or intrauterine insemination (IUI) in a prospective cohort study...
May 2012: Iranian Journal of Reproductive Medicine
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