In oncology, it is used as a tumor marker for monitoring patients with granulosa tumors. In the future, however, it is also promising to use the knowledge of AMH function for the treatment of gynecological as well as other solid malignancies expressing a tissue-specific receptor for AMH.

Increasing expression of Cdkn2a in control ovaries over time suggests a critical and yet unstudied role for senescence in folliculogenesis. The increasing expression of Cdkn2a in AKA ovaries suggests a potential role for senescence in endometriosis progression and, potentially, attenuation of the development of ovarian cancer. Primary granulosa cells offer an additional model to study these innovative results further.

Interestingly, the evaluation of oocyte developmental competence by in vitro culture of retrieved two-cell embryos indicated that oocytes originating from the Brg1fl/fl;Amhr2-Cre mice did not reach the blastocyst stage and had higher rates of mitotic defects, including micronuclei. Together, these results indicate that BRG1 plays an important role in female fertility by regulating granulosa and oocyte functions during follicle growth and is needed for the acquisition of oocyte developmental competence.

These results were compared favorably with results obtained using CFA as an adjuvant in the AMHR2-ED vaccine. Our data indicate that the AMHR2-ED vaccine formulated with AddaVax may be used in human clinical trials and thereby serve as a novel and effective way to control human EOC.

MIS/AMH inhibits the growth of MIS/AMH receptor-expressing endometrial cancer cells through regulation of autophagy, apoptosis, and cell cycle pathways, as well as inhibition of Wnt signaling pathways. These data suggest that MIS/AMH functions as a tumor suppressor and may be an effective therapeutic agent in endometrial cancer.

These results indicate that the epithelial LIFR-STAT3 pathway initiates the formation of implantation chambers, leading to complete blastocyst attachment, and that stromal STAT3 regulates blastocyst attachment without stromal LIFR control. Thus, uterine epithelial LIFR is critical to implantation chamber formation and blastocyst attachment.

This is the first report showing the presence of AMH (2,210 ng/ml) in ascites fluid, and it also shows that laparoscopic ovariectomy might not be suitable for larger ovaries affected by a GCT. Ultrasonographic, endocrine, and histopathological analyses were helpful for making a definitive diagnosis of GCT in this mare.

Overall, our results suggest that this embryonic receptor could be a suitable target for treating AMHRII-expressing tumors with an anti-AMHRII selective agent such as murlentamab, also named 3C23K or GM102. This potential therapeutic intervention was confirmed in vivo by showing antitumor activity of murlentamab against AMHRII-expressing colorectal cancer and hepatocarcinoma Patient-Derived tumor Xenografts (PDX) models.

Those mechanisms might contribute to the sustained clinical benefit observed in advanced cancer patients treated with murlentamab. Finally, the enhanced murlentamab activity in combination with pembrolizumab opens new therapeutic perspectives.

Previous mouse model with homozygous deletion of p53 gene and/or BRCA1 with Amhr2-Cre only had uterine leiomyosarcoma developed in approximately 50% of mice around 13 months without metastasis.RNAseq and RPPA functional data of the uterine leiomyosarcomas from our novel mouse models are being generated for comparison with known genomic profiles of human uterine leiomyosarcomas. The RNAseq and RPPA functional proteomic data from comparing uterine tissues from homozygous and heterozygous p53 mutated mice provide insight in the understanding the development of uterine leiomyosarcoma and for future clinical trials.

Furthermore, B10 reduced COV434-MISRII tumor growth in vivo and significantly enhanced the median survival time compared with vehicle (69 vs 60 days; p = 0.0173). Our data provide evidence for a novel pro-survival autocrine role of AMH in the context of ovarian cancer, which was targeted therapeutically using an anti-AMH antibody to successfully repress tumor growth.

Because UTF1, a specific marker of spermatogonial stem cell activity, was expressed in both the affected and unaffected sides in the testicular tissues of two patients, the risk of malignancy may be high in these patients. Although the etiology of TTE without PMDS remains unclear, our variant analysis results were consistent with previous reports, and variants in the AMH gene (rs10407022) may contribute to the specific phenotype of TTE without PMDS.

These mouse models will be useful for studying the differences in signaling pathways driven by Kras or Kras mutations to aid development of targeted therapies for specific KRAS mutant variants. Our leiomyoma model driven by the Kras mutation will also be useful in deciphering the malignant progression from leiomyoma to leiomyosarcoma.

Our results suggest that TMB plays an important role in the prognosis and guiding immunotherapy of OC. By detecting the TMB of OC, clinicians can more accurately treat patients with immunotherapy, thereby improving their survival rate.

We showed that autophagic deficit in the uterine vessel microenvironment provokes hyperpermeability through the deregulation of VEGFA, NOS1, and CTNNB1. ACTA2: actin, alpha 2, smooth muscle, aortic; Amhr2: anti-Mullerian hormone type 2 receptor; ANGPT1: angiopoietin 1; ATG: autophagy-related; CDH5: cadherin 5; CLDN5: claudin 5; COL1A1: collagen, type I, alpha 1; CSPG4/NG2: chondroitin sulfate proteoglycan 4; CTNNB1: catenin (cadherin associated protein), beta 1; DES: desmin; EDN1: endothelin 1; EDNRB: endothelin receptor type B; F3: coagulation factor III; KDR/FLK1/VEGFR2: kinase insert domain protein receptor; LYVE1: lymphatic vessel endothelial hyaluronan receptor 1; MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MCAM/CD146: melanoma cell adhesion molecule; MYL2: myosin, light polypeptide 2, regulatory, cardiac, slow; MYLK: myosin, light polypeptide kinase; NOS1/nNOS: nitric oxide synthase 1, neuronal; NOS2/iNOS: nitric oxide synthase 2, inducible; NOS3/eNOS: nitric oxide synthase 3, endothelial cell; OVX: ovariectomy; PECAM1/CD31: platelet/endothelial cell adhesion molecule 1; POSTN: periostin, osteoblast specific factor; SQSTM1: sequestosome 1; TEK/Tie2: TEK receptor tyrosine kinase; TJP1/ZO-1: tight junction protein 1; TUBB1, tubulin, beta 1 class VI; USC: uterine stromal cell; VEGFA: vascular endothelial growth factor A; VSMC: vascular smooth muscle cell.

Finally, using RNA sequencing, we identify several potential tumor suppressor genes that are reactivated by G9a inhibition in NB, including the CLU, FLCN, AMHR2, and AKR1C1-3. Together, our study underlines the under-appreciated role of G9a in NB, especially in MYCN-amplified tumors.

This study, which links IBM level with immunosuppression and tumor burden in peritoneum, identifies IBMs as apotential predictive signature of ascites immune status and as a biomarker ofovarian cancer development and treatment response.

Most importantly, the 4D12G1 mAb significantly inhibits growth of primary human EOCs in patient-derived xenografts (PDXs) by inducing direct apoptosis of EOC tumors. Our results support the view that a humanized 4D12G1 mAb may be a much needed and effective reagent for passive immunotherapy of human EOC.