scholarly journals Thyroid Hormone Signaling in Human Ovarian Surface Epithelial Cells

2007 ◽  
Vol 92 (1) ◽  
pp. 322-327 ◽  
Author(s):  
M. T. Rae ◽  
O. Gubbay ◽  
A. Kostogiannou ◽  
D. Price ◽  
H. O. D. Critchley ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Thyroid Hormone ◽  
Mrna Expression ◽  
Cell Cultures ◽  
Nuclear Hormone Receptor ◽  
Rt Pcr ◽  
Ovarian Surface ◽  
Increased Risk ◽  
Ovarian Surface Epithelial

Abstract Context: Ovarian surface epithelial (OSE) cells express multiple nuclear hormone receptor genes, including those encoding thyroid hormone and estrogen receptors (TR and ER, respectively). Ovarian cancer is hormone-dependent, and epidemiological evidence links hyperthyroidism, inflammation of the ovarian surface, and increased risk of ovarian cancer. Objective: The objective of this study was to assess T3 action on human OSE cells in vitro, asking 1) is there evidence for (pre)receptor control, 2) is T3 inflammatory, and 3) does T3 affect ER expression? Design: Immunohistochemical analysis of fixed human ovaries and in vitro analysis of human OSE primary cell cultures were performed. Patients: Twelve women aged 29–50 yr (median, 41 yr) undergoing elective gynecological surgery for nonmalignant conditions were studied. Results: Messenger RNA transcripts for TRα1, TRα2, TRβ1, and T3 activating deiodinase 2 and inactivating deiodinase 3 were present in primary OSE cell cultures by RT-PCR. TRα and TRβ proteins were also localized to intact OSE by immunohistochemistry. Treatment of OSE cell cultures for 24 h with T3 caused dose-dependent mRNA expression of inflammation-associated genes: cyclooxygenase-2, matrix metalloproteinase-9, and 11βhydroxysteroid dehydrogenase type 1, determined by quantitative RT-PCR. Finally, treatment with T3 dose dependently stimulated ERα mRNA expression without affecting ERβ1 or ERβ2. Conclusion: The ovarian surface is a potential T3 target. T3 exerts direct inflammatory effects on OSE cell function in vitro. OSE cell responses to T3 include increased expression of ERα mRNA, which encodes the ER isoform most strongly associated with ovarian cancer. This could help explain suggested epidemiological links between hyperthyroidism and ovarian cancer.

333 GENERATION OF OOCYTE-LIKE STRUCTURE FROM OVARIAN SURFACE EPITHELIAL STEM CELLS OF GOAT

2015 ◽  
Vol 27 (1) ◽  
pp. 255 ◽  
Author(s):  
S. Fatima ◽  
V. Sharma ◽  
S. Saini ◽  
S. Saugandhika ◽  
H. N. Malik ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endangered Species ◽  
Epithelial Cells ◽  
Ovarian Surface Epithelium ◽  
Surface Epithelium ◽  
Epithelial Stem Cells ◽  
Rt Pcr ◽  
Ovarian Surface ◽  
Ovarian Surface Epithelial

Stem cells have potential for therapeutic application. Continuous repair of ovarian surface epithelium following folliculogenesis and ovarian carcinoma suggests the presence of stem cells in ovarian epithelial cells. In vitro gametogenesis in livestock will result in large numbers of oocytes production from a single ovary, resulting in faster multiplication of superior germplasm of livestock species, treatment of infertile animals, and conservation of endangered species. The present study was conducted with the objective of in vitro differentiation of putative ovarian surface epithelial stem cells into oocyte-like structures in goat model. Ovary samples of 1- to 2-year-old goats were collected from slaughterhouse. The surface of the ovary was gently scraped using sterile blunt scraper to isolate ovarian surface epithelial stem cells. These scraped cells were cultured in DMEM/F12 supplemented with 20% FBS for 3 weeks in 5% CO2 at 37°C with maximum humidity. The cultured stem cells were characterised for stemness by RT-PCR and immunostaining for Oct4, Sox2, and Nanog genes after 3 weeks. These putative stem cells were in vitro differentiated spontaneously to oocyte-like structures in DMEM/F12 medium and characterised for premeiotic markers by RT-PCR and immunostaining for VASA, DAZL, and STELLA genes. Results of this study provide evidence for the presence of putative stem cells with pluripotent characteristics in the ovarian surface epithelium. The cultured cells were found to be round in shape, with a high nucleus to cytoplasm ratio under inverted microscope, and found positive for stem cell markers of Oct4, Sox2, and Nanog genes. A total of 66 oocyte-like structures were produced from 12 ovaries. These oocyte-like structures were nearly similar to oocytes produced in vivo, both morphologically and in molecular gene expression. The oocyte-like structures were also found positive for premeiotic markers of VASA, DAZL, and STELLA genes by RT-PCR and immunostaining. From this study, we concluded that the ovarian surface epithelial cells have putative stem cells which can be in vitro differentiated into oocyte-like structures in goat. These oocyte-like structures need further characterisation of their surface membrane, more molecular markers, and following their developmental potential. These oocytes can help for multiplication of elite germplasm, curing infertile animals, and saving endangered species.

In vitro model of normal, immortalized ovarian surface epithelial and ovarian cancer cells for chemoprevention of ovarian cancer

2005 ◽  
Vol 98 (2) ◽  
pp. 182-192 ◽  
Author(s):  
Molly Brewer ◽  
J. Taylor Wharton ◽  
Jian Wang ◽  
Amanda McWatters ◽  
Nelly Auersperg ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
In Vitro Model ◽  
Ovarian Cancer Cells ◽  
Ovarian Surface ◽  
Ovarian Surface Epithelial ◽  
Vitro Model

scholarly journals Cytocidal Antitumor Effects against Human Ovarian Cancer Cells Induced by B-Lactam Steroid Alkylators with Targeted Activity against Poly (ADP-Ribose) Polymerase (PARP) Enzymes in a Cell-Free Assay

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1028
Author(s):  
Nikolaos Nikoleousakos ◽  
Panagiotis Dalezis ◽  
Aikaterini Polonifi ◽  
Elena G. Geromichalou ◽  
Sofia Sagredou ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Cell Lines ◽  
Synthetic Lethality ◽  
Parp Inhibitor ◽  
Positive Control ◽  
Ovarian Cancer Cells ◽  
Antitumor Effects

We evaluated three newly synthesized B-lactam hybrid homo-aza-steroidal alkylators (ASA-A, ASA-B and ASA-C) for their PARP1/2 inhibition activity and their DNA damaging effect against human ovarian carcinoma cells. These agents are conjugated with an alkylating component (POPA), which also served as a reference molecule (positive control), and were tested against four human ovarian cell lines in vitro (UWB1.289 + BRCA1, UWB1.289, SKOV-3 and OVCAR-3). The studied compounds were thereafter compared to 3-AB, a known PARP inhibitor, as well as to Olaparib, a standard third-generation PARP inhibitor, on a PARP assay investigating their inhibitory potential. Finally, a PARP1 and PARP2 mRNA expression analysis by qRT-PCR was produced in order to measure the absolute and the relative gene expression (in mRNA transcripts) between treated and untreated cells. All the investigated hybrid steroid alkylators and POPA decreased in vitro cell growth differentially, according to the sensitivity and different gene characteristics of each cell line, while ASA-A and ASA-B presented the most significant anticancer activity. Both these compounds induced PARP1/2 enzyme inhibition, DNA damage (alkylation) and upregulation of PARP mRNA expression, for all tested cell lines. However, ASA-C underperformed on average in the above tasks, while the compound ASA-B induced synthetic lethality effects on the ovarian cancer cells. Nevertheless, the overall outcome, leading to a drug-like potential, provides strong evidence toward further evaluation.

THE RISK OF DEVELOPING GYNECOLOGICAL CANCER IN WOMEN AFTER AN IN VITRO FERTILIZATION PROGRAM

2021 ◽  
pp. 7-13
Author(s):  
Allakhyarov D.Z. ◽  
Petrov Yu.A. ◽  
Palieva N.V.
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Endometrial Cancer ◽  
In Vitro Fertilization ◽  
Gynecological Cancer ◽  
The Body ◽  
Fertilization Program ◽  
Vitro Fertilization ◽  
Increased Risk

This article presents reviews of literature sources on the issue of assessing the risk of developing gynecological cancer in women after an in vitro fertilization program. Infertility and infertile marriages have now become quite a big problem of modern medicine. Against the background of the unfavorable demographic situation in the Russian Federation, this problem is becoming quite urgent. The main way to solve this situation is assisted reproductive technologies, among which the most common is in vitro fertilization. The in vitro fertilization program is accompanied by a hormonal ovulation stimulation procedure to obtain a female germ cell capable of fertilization. Against the background of the active use of the in vitro fertilization procedure, many patients had concerns related to the risk of developing gynecological cancer after the IVF procedure, which is due to the use of hormonal drugs to stimulate the ovaries. Also of concern is the fact that certain types of cancer, including ovarian cancer, endometrial cancer and breast cancer, are hormone-dependent. In this regard, multiple large-scale studies were conducted, which showed that the risk of developing gynecological cancer is really increased in patients after the in vitro fertilization program. In particular, breast cancer in women after the in vitro fertilization program is more common by 10%, and in women without a history of pregnancy and over the age of 40, it is more common by 31%. The increased risk may be due to age-related vulnerability to the effects of hormones or higher doses of hormones during the IVF procedure. Ovarian cancer and endometrial cancer are also more common in patients after IVF. According to the research results, it is suggested that it is not the IVF procedure itself that causes the development of cancer, but excessive hormonal load of the body, which leads to the launch of carcinogenesis.

scholarly journals Role of Gonadotropin-Releasing Hormone as an Autocrine Growth Factor in Human Ovarian Surface Epithelium1

Endocrinology ◽  
2000 ◽  
Vol 141 (1) ◽  
pp. 72-80 ◽  
Author(s):  
Sung Keun Kang ◽  
Kyung-Chul Choi ◽  
Kwai Wa Cheng ◽  
Parimal S. Nathwani ◽  
Nelly Auersperg ◽  
...  
Keyword(s):  
Gnrh Agonist ◽  
Messenger Rna ◽  
Ovarian Surface Epithelium ◽  
Inhibitory Effect ◽  
Surface Epithelium ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Rt Pcr ◽  
Ovarian Surface ◽  
Ovarian Surface Epithelial

Abstract Epithelial ovarian cancer, which accounts for 80–90% of all ovarian cancers, is the most common cause of death from gynecological malignancies and is believed to originate from the ovarian surface epithelium. In the present study we investigated the expression of GnRH and its receptor in human ovarian surface epithelial (hOSE) cells and provided novel evidence that GnRH may have antiproliferative effects in this tissue. Using RT-PCR and Southern blot analysis, we cloned the GnRH and GnRH receptor (GnRHR) in hOSE cells. Sequence analysis revealed that GnRH and its receptor have sequences identical to those found in the hypothalamus and pituitary, respectively. To address whether GnRH regulates its own and receptor messenger RNA (mRNA), the cells were treated with different concentrations of the GnRH agonist (d-Ala6)-GnRH. Expression levels of GnRH and its receptor were investigated using quantitative and competitive RT-PCR, respectively. Interestingly, a biphasic effect was observed for the GnRH and GnRHR mRNA levels. High concentrations of the GnRH agonist (10−7 and 10−9m) decreased GnRH and GnRHR mRNA levels, whereas a low concentration (10−11m) resulted in up-regulation of GnRH and receptor mRNA levels. Treatment with the GnRH antagonist, antide, prevented the biphasic effects of the GnRH agonist in hOSE cells, confirming the specificity of the response. Furthermore, to investigate the physiological significance, we studied receptor-mediated growth regulatory effects of GnRH in human ovarian surface epithelial cells. The cells were treated with GnRH analogs, and the proliferative index of cells was measured using a [3H]thymidine incorporation assay. (d-Ala6)-GnRH had a direct inhibitory effect on the growth of hOSE cells in a time- and dose-dependent manner. This antiproliferative effect of the GnRH agonist was receptor mediated, as cotreatment of hOSE cells with antide abolished the growth inhibitory effects of the GnRH agonist. The results strongly suggest that GnRH can act as an autocrine/paracrine regulator in hOSE cells.

Colchicine attenuates inflammatory cell infiltration and extracellular matrix accumulation in diabetic nephropathy

2009 ◽  
Vol 297 (1) ◽  
pp. F200-F209 ◽  
Author(s):  
Jin Ji Li ◽  
Sun Ha Lee ◽  
Dong Ki Kim ◽  
Ri Jin ◽  
Dong-Sub Jung ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Diabetic Nephropathy ◽  
Mrna Expression ◽  
Inflammatory Cell ◽  
Renal Tissue ◽  
Inflammatory Cell Infiltration ◽  
Rt Pcr ◽  
Matrix Accumulation

Recent studies have demonstrated that an inflammatory mechanism contributes to the pathogenesis of diabetic nephropathy (DN). It is also known that colchicine (Col) can prevent various renal injuries via its anti-inflammatory action. However, the effect of colchicine on DN has never been explored. This study was undertaken to elucidate the effect of colchicine on inflammation and extracellular matrix accumulation in DN. In vivo, 64 rats were injected with diluent (C; n = 32) or streptozotocin intraperitoneally (DM, n = 32). Sixteen rats from each group were treated with Col. In vitro, rat mesangial cells and NRK-52E cells were cultured in media with 5.6 mM glucose (NG) or 30 mM glucose (HG) with or without 10−8M Col. Monocyte chemotactic protein-1 (MCP-1) mRNA expression was determined by real-time PCR (RT-PCR), and the levels of MCP-1 in renal tissue and culture media were measured by ELISA. RT-PCR and Western blotting were also performed for intercellular adhesion molecule-1 (ICAM-1) and fibronectin (FN) mRNA and protein expression, respectively, and immunohistochemical staining (IHC) for ICAM-1, FN, and ED-1 with renal tissue. Twenty-four-hour urinary albumin excretion at 6 wk and 3 mo were significantly higher in DM compared with C rats ( P < 0.05), and colchicine treatment significantly reduced albuminuria in DM rats ( P < 0.05). Col significantly inhibited the increase in MCP-1 mRNA expression and protein levels under diabetic conditions both in vivo and in vitro. ICAM-1 and FN expression showed a similar pattern to the expression of MCP-1. IHC revealed that the number of ED-1(+) cells were significantly higher in DM compared with C kidney ( P < 0.005), and this increase was significantly attenuated by Col treatment ( P < 0.01). In conclusion, Col prevents not only inflammatory cell infiltration via inhibition of enhanced MCP-1 and ICAM-1 expression but also ECM accumulation in DN. These findings provide a new perspective on the renoprotective effects of Col in DN.

scholarly journals SP1.1.7PBX4 functions as a novel oncogene and promotes angiogenesis in colorectal cancer: A comprehensive analysis of the PBX gene family

2021 ◽  
Vol 108 (Supplement_7) ◽  
Author(s):  
Eirini Martinou ◽  
Carla Moller-Levet ◽  
Izhar Bagwan ◽  
Guy Simpson ◽  
Lisiane Meira ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Survival Analysis ◽  
Gene Family ◽  
Mrna Expression ◽  
Comprehensive Analysis ◽  
Angiogenic Factor ◽  
Cell Leukaemia ◽  
Increased Risk

Abstract Aims Pre-B-cell Leukaemia (PBX) genes are important in organ development during embryogenesis. To date, four members of the PBX family (PBX1, PBX2, PBX3, PBX4) have been identified to be involved in human cancers, but little is known about their role in colorectal cancer (CRC). The aim of this study was to determine their differential expression, prognostic role and function in CRC. Methods Molecular and overall survival (OS) data from 614 patients with CRC were obtained from the National Cancer Institute, Tissue Cancer Genome Atlas (TCGA) database. To investigate the differential PBX gene mRNA expression, we performed a comparative cancer to normal computational analysis in edgeR. To determine PBXs prognostic value, we conducted Kaplan-Meier survival analysis and COX regression, selecting 10-year OS as primary outcome. Lastly, to explore the effect of PBX4 in CRC cell growth and angiogenesis, we performed gene expression modulation experiments using a PBX4-overexpressing plasmid-vector. Cell proliferation and VEGFA angiogenic factor expression were defined as primary and secondary in vitro outcomes respectively. Results Among PBXs only PBX4 was significantly upregulated showing a 4-fold increase in CRC vs normal colon (p &lt; 0.0001). Survival analysis showed that only high PBX4 mRNA expression was associated with increased risk for worse OS in patients with CRC (HR:1.3 95%CI:1-1.6, p = 0.02). Functionally, overexpression of PBX4 significantly increased CRC cell proliferation in vitro (p &lt; 0.001) and markedly upregulated the expression of VEGFA (p &lt; 0.0001). Conclusions Comprehensive analysis of the PBX gene family identifies that PBX4 may function as a novel oncogene and may promote angiogenesis through VEGFA in CRC.

scholarly journals Newly Developed Dual Topoisomerase Inhibitor P8-D6 is Highly Active in Ovarian Cancer

2021 ◽  
Author(s):  
Inken Flörkemeier ◽  
Tamara N. Steinhauer ◽  
Nina Hedemann ◽  
Magnus Ölander ◽  
Per Artursson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Topoisomerase I ◽  
Ex Vivo ◽  
Chemotherapy Resistance ◽  
Membrane Integrity ◽  
New Drugs ◽  
Highly Active ◽  
Ovarian Surface Epithelial ◽  
Gynaecologic Neoplasms

Abstract Background: Ovarian cancer (OvCa) constitutes a rare and highly aggressive malignancy and is one of the most lethal of all gynaecologic neoplasms. Due to chemotherapy resistance and treatment limitations because of side effects, OvCa is still not sufficiently treatable. Hence, new drugs for OvCa therapy such as P8-D6 with promising antitumour properties have a high clinical need. The benzo[c]phenanthridine P8-D6 is an effective inductor of apoptosis by acting as a dual topoisomerase I/II inhibitor. Methods: In the present study, the effectiveness of P8-D6 on OvCa was investigated in vitro. In various OvCa cell lines and ex vivo primary cells, the apoptosis induction compared to standard therapeutic agents was determined in 2D monolayers. Expanded by 3D and co-culture, the P8-D6 treated cells were examined for changes in cytotoxicity, apoptosis rate and membrane integrity via scanning electron microscopy (SEM). Likewise, the effects of P8-D6 on non-cancer human ovarian surface epithelial cells and primary human hepatocytes were determined. Results: This study shows a significant P8-D6-induced increase in apoptosis and cytotoxicity in OvCa cells which surpasses the efficacy of standard therapeutic drugs. Non-cancer cells were affected only slightly by P8-D6. Moreover, no hepatotoxic effect in in vitro studies was detected.Conclusions: P8-D6 is a strong and rapid inductor of apoptosis and might be a novel treatment option for OvCa therapy.

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