scholarly journals A Review of the Clinical Characteristics and Novel Molecular Subtypes of Endometrioid Ovarian Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Shuangfeng Chen ◽  
Yuebo Li ◽  
Lili Qian ◽  
Sisi Deng ◽  
Luwen Liu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Reproductive Tract ◽  
Molecular Subtypes ◽  
Female Reproductive Tract ◽  
Molecular Characteristics ◽  
The Novel ◽  
Endometrioid Ovarian Carcinoma ◽  
Endometrioid Ovarian Cancer ◽  
Prediction Of Prognosis ◽  
Novel Therapeutic Strategies

Ovarian cancer is one of the most common gynecologic cancers that has the highest mortality rate. Endometrioid ovarian cancer, a distinct subtype of epithelial ovarian cancer, is associated with endometriosis and Lynch syndrome, and is often accompanied by synchronous endometrial carcinoma. In recent years, dysbiosis of the microbiota within the female reproductive tract has been suggested to be involved in the pathogenesis of endometrial cancer and ovarian cancer, with some specific pathogens exhibiting oncogenic having been found to contribute to cancer development. It has been shown that dysregulation of the microenvironment and accumulation of mutations are stimulatory factors in the progression of endometrioid ovarian carcinoma. This would be a potential therapeutic target in the future. Simultaneously, multiple studies have demonstrated the role of four molecular subtypes of endometrioid ovarian cancer, which are of particular importance in the prediction of prognosis. This literature review aims to compile the potential mechanisms of endometrioid ovarian cancer, molecular characteristics, and molecular pathological types that could potentially play a role in the prediction of prognosis, and the novel therapeutic strategies, providing some guidance for the stratified management of ovarian cancer.

Wnt-7a maintains appropriate uterine patterning during the development of the mouse female reproductive tract

Development ◽  
1998 ◽  
Vol 125 (16) ◽  
pp. 3201-3211 ◽  
Author(s):  
C. Miller ◽  
D.A. Sassoon
Keyword(s):  
Reproductive Tract ◽  
Hox Genes ◽  
Cell Types ◽  
Female Reproductive Tract ◽  
Molecular Characteristics ◽  
Anteroposterior Patterning ◽  
Stratified Epithelium ◽  
Distinct Cell ◽  
Hoxa Gene Expression ◽  
Posterior Shift

The murine female reproductive tract differentiates along the anteroposterior axis during postnatal development. This process is marked by the emergence of distinct cell types in the oviduct, uterus, cervix and vagina and is dependent upon specific mesenchymal-epithelial interactions as demonstrated by earlier heterografting experiments. Members of the Wnt family of signaling molecules have been recently identified in this system and an early functional role in reproductive tract development has been demonstrated. Mice were generated using ES-mediated homologous recombination for the Wnt-7a gene (Parr, B. A. and McMahon, A. P. (1995) Nature 374, 350–353). Since Wnt-7a is expressed in the female reproductive tract, we examined the developmental consequences of lack of Wnt-7a in the female reproductive tract. We observe that the oviduct lacks a clear demarcation from the anterior uterus, and acquires several cellular and molecular characteristics of the uterine horn. The uterus acquires cellular and molecular characteristics that represent an intermediate state between normal uterus and vagina. Normal vaginas have stratified epithelium and normal uteri have simple columnar epithelium, however, mutant uteri have stratified epithelium. Additionally, Wnt-7a mutant uteri do not form glands. The changes observed in the oviduct and uterus are accompanied by a postnatal loss of hoxa-10 and hoxa-11 expression, revealing that Wnt-7a is not required for early hoxa gene expression, but is required for maintenance of expression. These clustered hox genes have been shown to play a role in anteroposterior patterning in the female reproductive tract. In addition to this global posterior shift in the female reproductive tract, we note that the uterine smooth muscle is disorganized, indicating development along the radial axis is affected. Changes in the boundaries and levels of other Wnt genes are detectable at birth, prior to changes in morphologies. These results suggest that a mechanism whereby Wnt-7a signaling from the epithelium maintains the molecular and morphological boundaries of distinct cellular populations along the anteroposterior and radial axes of the female reproductive tract.

scholarly journals Novel Molecular Subtypes of Serous and Endometrioid Ovarian Cancer Linked to Clinical Outcome

2008 ◽  
Vol 14 (16) ◽  
pp. 5198-5208 ◽  
Author(s):  
Richard W. Tothill ◽  
Anna V. Tinker ◽  
Joshy George ◽  
Robert Brown ◽  
Stephen B. Fox ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Outcome ◽  
Molecular Subtypes ◽  
Endometrioid Ovarian Cancer

scholarly journals Pretreatment with LCK Inhibitors Chemosensitizes Cisplatin-Resistant Endometrioid Ovarian Tumors

2020 ◽  
Author(s):  
Katie K. Crean-Tate ◽  
Chad Braley ◽  
Goutam Dey ◽  
Emily Esakov ◽  
Caner Saygin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Viability ◽  
Ovarian Carcinoma ◽  
Survival Data ◽  
Ovarian Tumors ◽  
Platinum Resistant ◽  
Endometrioid Ovarian Carcinoma ◽  
Endometrioid Ovarian Cancer ◽  
Km Plotter

AbstractObjectiveTo evaluate LCK inhibitors (LCKi) as chemosensitizing agents for platinum-resistant endometrioid ovarian carcinoma.MethodsKM Plotter survival data was obtained for endometrioid ovarian cancer based on LCK mRNA expression. Cisplatin resistant endometrioid ovarian carcinoma cell lines were cultured and treated first with LCKi or vehicle, then combination LCKi-cisplatin. Cell viability was assessed via CellTiter-Glo, and apoptosis with Caspase 3/7 Assay. Protein lysates were isolated from treated cells, with γ-H2Ax, a DNA adduct marker, assessed. In vivo study compared mice treated with vehicle or LCK inhibitor followed by LCK inhibitor, cisplatin, or combination therapy. One-way ANOVA and two sample t-test were used to assess statistical significance with GraphPad Prism.ResultsKM plotter data indicated LCK expression is associated with significantly worse median progression-free survival (HR 3.19, p=0.02), and a trend toward decreased overall survival in endometrioid ovarian tumors with elevated LCK expression (HR 2.45, p=0.41). In vitro, cisplatin resistant ovarian endometrioid cells treated first with LCKi followed by combination LCKi-cisplatin treatment showed decreased cell viability and increased apoptosis. Immunoblot studies revealed inhibition of LCK led to increased expression of γ-H2AX. In vivo results demonstrate treatment with LCKi followed by LCKi-cisplatin leads to significantly slowed tumor growth.ConclusionsWe identified a targetable pathway for chemosensitization of platinum resistant endometrioid ovarian cancer with initial treatment of LCKi followed by co-treatment with LCKi-cisplatin.

scholarly journals UNC-45A Is Highly Expressed in the Proliferative Cells of the Mouse Genital Tract and in the Microtubule-Rich Areas of the Mouse Nervous System

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1604
Author(s):  
Valentino Clemente ◽  
Asumi Hoshino ◽  
Joyce Meints ◽  
Mihir Shetty ◽  
Tim Starr ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Central Nervous System ◽  
Nervous System ◽  
Genital Tract ◽  
Reproductive Tract ◽  
Neuronal Development ◽  
Female Reproductive Tract ◽  
Ciliated Epithelium ◽  
Actomyosin Contractility ◽  
Cancer Initiation

UNC-45A (Protein unc-45 homolog A) is a cytoskeletal-associated protein with a dual and non-mutually exclusive role as a regulator of the actomyosin system and a Microtubule (MT)-destabilizing protein, which is overexpressed in human cancers including in ovarian cancer patients resistant to the MT-stabilizing drug paclitaxel. Mapping of UNC-45A in the mouse upper genital tract and central nervous system reveals its enrichment not only in highly proliferating and prone to remodeling cells, but also in microtubule-rich areas, of the ovaries and the nervous system, respectively. In both apparatuses, UNC-45A is also abundantly expressed in the ciliated epithelium. As regulators of actomyosin contractility and MT stability are essential for the physiopathology of the female reproductive tract and of neuronal development, our findings suggest that UNC-45A may have a role in ovarian cancer initiation and development as well as in neurodegeneration.

scholarly journals Functional Analysis of Non-Genetic Resistance to Platinum in Epithelial Ovarian Cancer Reveals a Role for the MBD3-NuRD Complex in Resistance Development

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3801
Author(s):  
Tabea L. Bauer ◽  
Katrin Collmar ◽  
Till Kaltofen ◽  
Ann-Katrin Loeffler ◽  
Lorena Decker ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cell Lines ◽  
Reproductive Tract ◽  
Genetic Resistance ◽  
Female Reproductive Tract ◽  
Nurd Complex ◽  
Nucleosome Remodeling ◽  
Independent Prognostic Marker ◽  
Novel Biomarkers

Epithelial ovarian cancer (EOC) is the most lethal disease of the female reproductive tract, and although most patients respond to the initial treatment with platinum (cPt)-based compounds, relapse is very common. We investigated the role of epigenetic changes in cPt-sensitive and -resistant EOC cell lines and found distinct differences in their enhancer landscape. Clinical data revealed that two genes (JAK1 and FGF10), which gained large enhancer clusters in resistant EOC cell lines, could provide novel biomarkers for early patient stratification with statistical independence for JAK1. To modulate the enhancer remodeling process and prevent the acquisition of cPt resistance in EOC cells, we performed a chromatin-focused RNAi screen in the presence of cPt. We identified subunits of the Nucleosome Remodeling and Deacetylase (NuRD) complex as critical factors sensitizing the EOC cell line A2780 to platinum treatment. Suppression of the Methyl-CpG Binding Domain Protein 3 (MBD3) sensitized cells and prevented the establishment of resistance under prolonged cPt exposure through alterations of H3K27ac at enhancer regions, which are differentially regulated in cPt-resistant cells, leading to a less aggressive phenotype. Our work establishes JAK1 as an independent prognostic marker and the NuRD complex as a potential target for combinational therapy.

scholarly journals UNC-45A is Highly Expressed in the Proliferative Cells of the Mouse Genital Tract and in the Microtubule-Rich Areas of the Mouse Nervous System

2021 ◽  
Author(s):  
Valentino Clemente ◽  
Asumi Hoshino ◽  
Joyce Meints ◽  
Mihir Shetty ◽  
Tim Starr ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Central Nervous System ◽  
Nervous System ◽  
Cancer Patients ◽  
Genital Tract ◽  
Reproductive Tract ◽  
Neuronal Development ◽  
Female Reproductive Tract ◽  
Ciliated Epithelium ◽  
Cancer Initiation

AbstractUNC-45A is a cytoskeletal-associated protein with a dual and non-mutually exclusive role as a regulator of the acto-myosin system and as a Microtubule (MT)-destabilizing protein. UNC-45A is overexpressed in human cancers including in ovarian cancer patients resistant to the MT-stabilizing drug Paclitaxel. Mapping of UNC-45A in the mouse upper genital tract and central nervous system reveals its enrichment in highly proliferating and prone to remodeling cells and in microtubule-rich areas of in the ovaries and in neurons respectively. In both apparatuses UNC-45A is also abundantly expressed in the ciliated epithelium. Because regulators of acto-myosin contractility and MT stability are essential for the physiopathology of the female reproductive tract and of neuronal development our findings suggest that UNC-45A may have a role in ovarian cancer initiation and development and in neurodegeneration.

scholarly journals NIS Mediates Iodide Uptake in the Female Reproductive Tract and Is a Poor Prognostic Factor in Ovarian Cancer

2014 ◽  
Vol 99 (7) ◽  
pp. E1199-E1208 ◽  
Author(s):  
Garcilaso Riesco-Eizaguirre ◽  
Suzana Garcia Leoni ◽  
Marta Mendiola ◽  
Maria Angeles Estevez-Cebrero ◽  
Marta Ines Gallego ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Prognostic Factor ◽  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Iodide Uptake ◽  
Poor Prognostic Factor

scholarly journals High-Grade Serous Ovarian Cancer: Basic Sciences, Clinical and Therapeutic Standpoints

2019 ◽  
Vol 20 (4) ◽  
pp. 952 ◽  
Author(s):  
Michael-Antony Lisio ◽  
Lili Fu ◽  
Alicia Goyeneche ◽  
Zu-hua Gao ◽  
Carlos Telleria
Keyword(s):  
Ovarian Cancer ◽  
Reproductive Tract ◽  
Scientific Discovery ◽  
Molecular Genetic ◽  
Treatment Strategies ◽  
Female Reproductive Tract ◽  
Clinical Aspects ◽  
Anatomical Site ◽  
High Grade ◽  
Serous Ovarian Cancer

Among a litany of malignancies affecting the female reproductive tract, that of the ovary is the most frequently fatal. Moreover, while the steady pace of scientific discovery has fuelled recent ameliorations in the outcomes of many other cancers, the rates of mortality for ovarian cancer have been stagnant since around 1980. Yet despite the grim outlook, progress is being made towards better understanding the fundamental biology of this disease and how its biology in turn influences clinical behaviour. It has long been evident that ovarian cancer is not a unitary disease but rather a multiplicity of distinct malignancies that share a common anatomical site upon presentation. Of these, the high-grade serous subtype predominates in the clinical setting and is responsible for a disproportionate share of the fatalities from all forms of ovarian cancer. This review aims to provide a detailed overview of the clinical-pathological features of ovarian cancer with a particular focus on the high-grade serous subtype. Along with a description of the relevant clinical aspects of this disease, including novel trends in treatment strategies, this text will inform the reader of recent updates to the scientific literature regarding the origin, aetiology and molecular-genetic basis of high-grade serous ovarian cancer (HGSOC).

scholarly journals Molecular Evolution of CatSper in Mammals and Function of Sperm Hyperactivation in Gray Short-Tailed Opossum

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1047
Author(s):  
Jae Yeon Hwang ◽  
Jamie Maziarz ◽  
Günter P. Wagner ◽  
Jean-Ju Chung
Keyword(s):  
Molecular Evolution ◽  
Reproductive Tract ◽  
Sequence Divergence ◽  
Monodelphis Domestica ◽  
Female Reproductive Tract ◽  
Molecular Characteristics ◽  
High Sequence Divergence ◽  
And Function ◽  
Motility Change ◽  
First Time

Males have evolved species-specifical sperm morphology and swimming patterns to adapt to different fertilization environments. In eutherians, only a small fraction of the sperm overcome the diverse obstacles in the female reproductive tract and successfully migrate to the fertilizing site. Sperm arriving at the fertilizing site show hyperactivated motility, a unique motility pattern displaying asymmetric beating of sperm flagella with increased amplitude. This motility change is triggered by Ca2+ influx through the sperm-specific ion channel, CatSper. However, the current understanding of the CatSper function and its molecular regulation is limited in eutherians. Here, we report molecular evolution and conservation of the CatSper channel in the genome throughout eutherians and marsupials. Sequence analyses reveal that CatSper proteins are slowly evolved in marsupials. Using an American marsupial, gray short-tailed opossum (Monodelphis domestica), we demonstrate the expression of CatSper in testes and its function in hyperactivation and unpairing of sperm. We demonstrate that a conserved IQ-like motif in CatSperζ is required for CatSperζ interaction with the pH-tuned Ca2+ sensor, EFCAB9, for regulating CatSper activity. Recombinant opossum EFCAB9 can interact with mouse CatSperζ despite high sequence divergence of CatSperζ among CatSper subunits in therians. Our finding suggests that molecular characteristics and functions of CatSper are evolutionarily conserved in gray short-tailed opossum, unraveling the significance of sperm hyperactivation and fertilization in marsupials for the first time.

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