https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 Extracellular matrix in high-grade serous ovarian cancer: Advances in understanding of carcinogenesis and cancer biology https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51421 Wed 28 Feb 2024 15:25:16 AEDT ]]> Establishment and characterization of oviductal organoids from farm and companion animals(dagger) https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53095 Wed 27 Mar 2024 12:12:14 AEDT ]]> In Vivo cell fate tracing provides no evidence for mesenchymal to epithelial transition in adult fallopian tube and uterus https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37510 Wed 19 Jan 2022 15:15:31 AEDT ]]> In vivo genetic cell lineage tracing reveals that oviductal secretory cells self-renew and give rise to ciliated cells https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34201 In vivo genetic cell lineage tracing showed that secretory cells not only self-renew, but also give rise to ciliated cells. Analysis of a Wnt reporter mouse model and various Wnt target genes showed that the Wnt signaling pathway is involved in oviductal epithelial homoeostasis. By developing two triple-transgenic mouse models, we showed that Wnt/ ß-catenin signaling is essential for self-renewal as well as the differentiation of secretory cells. In summary, our results provide mechanistic insight into oviductal epithelial homoeostasis.]]> Wed 19 Jan 2022 15:14:57 AEDT ]]> Germ cell-specific sustained activation of Wnt signalling perturbs spermatogenesis in aged mice, possibly through non-coding RNAs https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29868 Wed 15 Dec 2021 16:08:58 AEDT ]]> Cell lineage tracing identifies hormone-regulated and Wnt-responsive vaginal epithelial stem cells https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38201 Wed 11 Aug 2021 10:05:47 AEST ]]> Stromal liver kinase B1 STK11 signaling loss induces oviductal adenomas and endometrial cancer by activating mammalian target of Rapamycin Complex 1 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:15121 Wed 11 Apr 2018 14:09:49 AEST ]]> Inhibition of extracellular matrix mediated TGF-β signalling suppresses endometrial cancer metastasis https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30784 Wed 11 Apr 2018 13:21:37 AEST ]]> Germ cell specific overactivation of WNT/βcatenin signalling has no effect on folliculogenesis but causes fertility defects due to abnormal foetal development https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29296 DEAD (Asp-Glu-Ala-Asp) box protein 4 (Ddx4) gene promoter. Histopathological and functional analysis of ovaries from these mutant mice (Ctnnb1ex3cko) showed no defects in ovarian functions, oocytes, ovulation and early embryonic development. However, breeding of the Ctnnb1ex3cko female mice with males of known fertility never resulted in birth of mutant pups. Examination of uteri from time pregnant mutant females revealed defects in ectoderm differentiation leading to abnormal foetal development and premature death. Collectively, our work has established the role of active WNT/βcatenin signalling in oocyte biology and foetal development, and provides novel insights into the possible mechanisms of complications in human pregnancy such as repeated spontaneous abortion, sudden intrauterine unexpected foetal death syndrome and stillbirth.]]> Wed 11 Apr 2018 13:03:48 AEST ]]> Mesoporous Carbon Nitrides as Emerging Materials: Nanoarchitectonics and Biosensing Applications https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53691 Wed 10 Jan 2024 10:34:44 AEDT ]]> Overactive mTOR signaling leads to endometrial hyperplasia in aged women and mice https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30999 Wed 09 Feb 2022 15:59:25 AEDT ]]> Ovarian hormones through Wnt signalling regulate the growth of human and mouse ovarian cancer initiating lesions https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29580 BRCA1/2 mutations have a genetic predisposition for developing OC, but not all of these women develop the disease. Epidemiological findings show that lifestyle factors such as contraceptive use and pregnancy, a progesterone dominant state, decrease the risk of getting OC. How ovarian hormones modify the risk of OC is currently unclear. Our study identifies activated Wnt signalling to be a marker for precursor lesions of OC and successfully develops a mouse model that mimics the earliest events in pathogenesis of OC by constitutively activating ßcatenin. Using this model and human OC cells, we show that oestrogen promotes and progesterone suppresses the growth of OC cells.]]> Wed 09 Feb 2022 15:54:46 AEDT ]]> Adipose-Derived VEGF–mTOR Signaling Promotes Endometrial Hyperplasia and Cancer: Implications for Obese Women https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:43015 Wed 09 Aug 2023 12:26:25 AEST ]]> Proteomic and functional characterization of intra-tumor heterogeneity in human endometrial cancer https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50850 Wed 09 Aug 2023 09:39:07 AEST ]]> Schwann cell stimulation of pancreatic cancer cells: a proteomic analysis https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37505 Wed 02 Mar 2022 14:28:59 AEDT ]]> Interferon-epsilon is a novel regulator of NK cell responses in the uterus https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:55703 Tue 18 Jun 2024 12:51:29 AEST ]]> Age related increase in mTOR activity contributes to the pathological changes in ovarian surface epithelium https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29966 Thu 28 Oct 2021 13:04:58 AEDT ]]> Development and characterization of human fetal female reproductive tract organoids to understand Müllerian duct anomalies https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53981 Thu 25 Jan 2024 12:57:12 AEDT ]]> The emerging role of the microenvironment in endometrial cancer https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36332 Thu 24 Mar 2022 11:36:03 AEDT ]]> Mass Spectrometry Proteomic Analysis of Four p53 Patterns in Differentiated Vulvar Intraepithelial Neoplasia https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49981 Thu 22 Jun 2023 11:59:40 AEST ]]> Oestrogen fuels the growth of endometrial hyperplastic lesions initiated by overactive Wnt/β-catenin signalling https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:43322 Thu 15 Sep 2022 14:43:38 AEST ]]> Endometrial Axin2+ cells drive epithelial homeostasis, regeneration, and cancer following oncogenic transformation https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:46824 in vivo lineage tracing to show that endometrial epithelium self-renews during development, growth, and regeneration and identified Axin2, a classical Wnt reporter gene, as a marker of long-lived bipotent epithelial progenitors that reside in endometrial glands. Axin2-expressing cells are responsible for epithelial regeneration in vivo and for endometrial organoid development in vitro. Ablation of Axin2+ cells severely impairs endometrial homeostasis and compromises its regeneration. More important, upon oncogenic transformation, these cells can lead to endometrial cancer. These findings provide valuable insights into the cellular basis of endometrial functions and diseases.]]> Thu 01 Dec 2022 10:59:01 AEDT ]]> Proteomic characterization of the extracellular matrix of human uterine fibroids https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41255 Sat 30 Jul 2022 13:01:25 AEST ]]> PTEN loss and HOXA10 expression are associated with ovarian endometrioid adenocarcinoma differentiation and progression https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:18989 Sat 24 Mar 2018 08:05:33 AEDT ]]> Altered LKB1/AMPK/TSC1/TSC2/mTOR signaling causes disruption of sertoli cell polarity and spermatogenesis https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21602 cko) in somatic testicular cells to define the molecular mechanisms involved in the development of the testicular phenotype observed in PJS patients. Focal vacuolization in some of the seminiferous tubules was observed in 4-week-old mutant testes but germ cell development appeared to be normal. However, similar to PJS patients, we observed progressive germ cell loss and Sertoli cell only tubules in Lkb1cko testes from mice older than 10 weeks, accompanied by defects in Sertoli cell polarity and testicular junctional complexes and decreased activation of the MAP/microtubule affinity regulating and focal adhesion kinases. Suppression of AMP kinase and activation of mammalian target of rapamycin (mTOR) signaling were also observed in Lkb1cko testes. Loss of Tsc1 or Tsc2 copies the progressive Lkb1cko phenotype, suggesting that dysregulated activation of mTOR contributes to the pathogenesis of the Lkb1cko testicular phenotype. Ptencko mice had a normal testicular phenotype, which could be explained by the comparative lack of mTOR activation detected. These studies describe the importance of LKB1 signaling in testicular biology and the possible molecular mechanisms driving the pathogenesis of the testicular defects observed in PJS patients.]]> Sat 24 Mar 2018 07:59:37 AEDT ]]> Loss of LKB1 and PTEN tumor suppressor genes in the ovarian surface epithelium induces papillary serous ovarian cancer https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20682 Sat 24 Mar 2018 07:55:42 AEDT ]]> Epithelial Wnt/βcatenin signalling is essential for epididymal coiling https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:25924 in vitro treatment with Fgf7 protein increased coiling of WDs. In summary, our work has established that epithelial canonical Wnt signalling is a critical regulator of WD coiling and its precise regulation is essential for WD/epididymal differentiation.]]> Sat 24 Mar 2018 07:27:51 AEDT ]]> Axin2(+) endometrial stem cells: the source of endometrial regeneration and cancer https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:43020 Mon 12 Sep 2022 09:32:47 AEST ]]> Deciphering the influence of mare oviductal organoid secretions on equine spermatozoa https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54093 Mon 05 Feb 2024 09:20:48 AEDT ]]> Extracellular matrix (ECM) activates β-catenin signaling in uterine fibroids https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44716 Fri 21 Oct 2022 09:04:25 AEDT ]]> Differential Wnt signaling activity limits epithelial gland development to the anti-mesometrial side of the mouse uterus https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:33850 Fri 18 Jan 2019 14:48:51 AEDT ]]> Canonical Wnt/β-catenin signaling regulates postnatal mouse epididymal development but does not affect epithelial cell differentiation https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:33847 Fri 18 Jan 2019 14:48:50 AEDT ]]> Prevalence and clinical significance of co-existing mutations in MED12 and FH in uterine fibroids of Australian women https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53114 Fri 17 Nov 2023 11:41:36 AEDT ]]> Proteomic profiling of human uterine fibroids reveals upregulation of the extracellular matrix protein periostin https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35929 MED12 alterations in 39 of 65 fibroids (60%) from 14 patients. Using isobaric tagged-based quantitative mass spectrometry on three selected patients (n = 9 fibroids), we observed a common set of upregulated ( > 1.5-fold) and downregulated ( < 0.66-fold) proteins in small, medium, and large fibroid samples of annotated MED12 status. These two sets of upregulated and downregulated proteins were the same in all patients, regardless of variations in fibroid size and MED12 status. We then focused on one of the significant upregulated ECM proteins and confirmed the differential expression of periostin using western blotting and immunohistochemical analysis. Our study defined the proteome of uterine fibroids and identified that increased ECM protein expression, in particular periostin, is a hallmark of uterine fibroids regardless of MED12 mutation status. This study sets the foundation for further investigations to analyze the mechanisms regulating ECM overexpression and the functional role of upregulated ECM proteins in leiomyogenesis.]]> Fri 17 Jan 2020 11:35:08 AEDT ]]> Specific deletion of LKB1/Stk11 in the Müllerian duct mesenchyme drives hyperplasia of the periurethral stroma and tumorigenesis in male mice https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34624 CKO mice by conditional deletion of the liver kinase B1 (LKB1) tumor suppressor gene, Stk11 (serine threonine kinase 11), in the fetal Müllerian duct mesenchyme (MDM), the caudal remnant of which is thought to be assimilated by the urogenital sinus primordial mesenchyme in males during fetal development. We show that MDM cells contribute to the postnatal stromal cells at the dorsal aspect of the prostatic urethra by lineage tracing. The Stk11CKO mice develop prostatic hyperplasia with bladder outlet obstruction, most likely because of stromal expansion. The stromal areas from prostates of Stk11CKO mice, with or without significant expansion, were estrogen receptor positive, which is consistent with both MD mesenchyme-derived cells and the purported importance of estrogen receptors in BPH development and/or progression. In some cases, stromal hyperplasia was admixed with epithelial metaplasia, sometimes with keratin pearls, consistent with squamous cell carcinomas. Mice with conditional deletion of both Stk11 and Pten developed similar features as the Stk11CKO mice, but at a highly accelerated rate, often within the first few months after birth. Western blot analyses showed that the loss of LKB1 and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) induces activation of the phospho-5' adenosine monophosphateactivated protein kinase and phospho-AKT serine/threonine kinase 1 signaling pathways, as well as increased total and active ß-catenin. These results suggest that activation of these signaling pathways can induce hyperplasia of the MD stroma, which could play a significant role in the etiology of human BPH.]]> Fri 05 Apr 2019 11:33:46 AEDT ]]> Proteomic analysis identifies tenascin-C expression is upregulated in uterine fibroids https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45565 1.5-fold) with a confidence corresponding to false discovery rate (FDR) <1% in small-, medium-, and large-sized fibroid samples regardless of MED12 mutation status. The TNC was validated on additional patient samples using Western blotting (WB) and immunohistochemistry (IHC) and confirmed significant overexpression of this protein in fibroids compared to matched ANM. Proteomic analyses have identified the increased ECM protein expression, TNC, as a hallmark of uterine fibroids regardless of MED12 mutations. Further functional studies focusing on the upregulated ECM proteins in leiomyogenesis will lead to the identification of novel ECM drug targets for fibroid treatment.]]> Fri 04 Nov 2022 14:44:56 AEDT ]]> Extracellular matrix-mediated regulation of cancer stem cells and chemoresistance https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47881 Fri 03 Feb 2023 15:52:53 AEDT ]]> Bovine and human endometrium-derived hydrogels support organoid culture from healthy and cancerous tissues https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51354 Fri 01 Sep 2023 13:44:28 AEST ]]> Loss of liver kinase B1 in human seminoma https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51353 Fri 01 Sep 2023 13:35:36 AEST ]]>