Hormonal therapy in ovarian cancer

2007 ◽  
Vol 17 (2) ◽  
pp. 325-338 ◽  
Author(s):  
H. Zheng ◽  
J. J. Kavanagh ◽  
W. Hu ◽  
Q. Liao ◽  
S. Fu
Keyword(s):  
Ovarian Cancer ◽  
Hormonal Therapy ◽  
Experimental Studies ◽  
Epidemiologic Studies ◽  
Ovarian Cancer Cells ◽  
Gynecological Malignancy ◽  
Cancer Pathogenesis ◽  
Ovarian Carcinogenesis ◽  
Growth Inhibitory ◽  
Causative Factors

Ovarian carcinoma continues to be the leading cause of death due to gynecological malignancy. Epidemiologic studies indicate that steroid hormones play roles in ovarian carcinogenesis. Gonadotropins, estrogen, and androgen may be causative factors, while gonadotropin-releasing hormone and progesterone may be protective factors in ovarian cancer pathogenesis. Experimental studies have shown that hormonal receptors are expressed in ovarian cancer cells and mediate the growth-stimulatory or growth-inhibitory effects of the hormones on these cells. Hormonal therapeutic agents have been evaluated in several clinical trials. Most of these trials were conducted in patients with recurrent or refractory ovarian cancer, with modest efficacy and few side effects. Better understanding of the mechanisms through which hormones affect cell growth may improve the efficacy of hormonal therapy. Molecular markers that can reliably predict major clinical outcomes should be investigated further in well-designed trials

scholarly journals Cell growth inhibitory effects of polyphenols with naphthalene skeleton against cisplatin-resistant ovarian cancer cells

2018 ◽  
Vol 61 (6) ◽  
pp. 697-701 ◽  
Author(s):  
Soon Young Shin ◽  
Youngshim Lee ◽  
Jihyun Park ◽  
Doseok Hwang ◽  
Geunhyeong Jo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Inhibitory Effects ◽  
Growth Inhibitory

scholarly journals HOTTIP-miR-205-ZEB2 Axis Confers Cisplatin Resistance to Ovarian Cancer Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Yu-Jie Dong ◽  
Wei Feng ◽  
Yan Li
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Clinical Problem ◽  
Ovarian Cancer Cells ◽  
Stem Cell Markers ◽  
Gene Target ◽  
Gynecological Malignancy ◽  
Clonogenic Potential ◽  
Resistant Cells

Ovarian cancer is a deadly gynecological malignancy with resistance to cisplatin a major clinical problem. We evaluated a role of long non-coding (lnc) RNA HOTTIP (HOXA transcript at the distal tip) in the cisplatin resistance of ovarian cancer cells, using paired cisplatin sensitive and resistant A2780 cells along with the SK-OV-3 cells. HOTTIP was significantly elevated in cisplatin resistant cells and its silencing reversed the cisplatin resistance of resistant cells. HOTTIP was found to sponge miR-205 and therefore HOTTIP silenced cells had higher levels of miR-205. Downregulation of miR-205 could attenuate HOTTIP-silencing effects whereas miR-205 upregulation in resistant cells was found to re-sensitize cells to cisplatin. HOTTIP silencing also led to reduced NF-κB activation, clonogenic potential and the reduced expression of stem cell markers SOX2, OCT4, and NANOG, an effect that could be attenuated by miR-205. Finally, ZEB2 was identified as the gene target of miR-205, thus completing the elucidation of HOTTIP-miR-205-ZEB2 as the novel axis which is functionally involved in the determination of cisplatin resistance in ovarian cancer cells.

scholarly journals The metabolic stress-activated checkpoint LKB1-MARK3 axis acts as a tumor suppressor in high-grade serous ovarian carcinoma

2022 ◽  
Vol 5 (1) ◽  
Author(s):  
Hidenori Machino ◽  
Syuzo Kaneko ◽  
Masaaki Komatsu ◽  
Noriko Ikawa ◽  
Ken Asada ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Cell Cycle Progression ◽  
Target Genes ◽  
Metabolic Stress ◽  
Ovarian Cancer Cells ◽  
Hippo Signaling ◽  
High Grade ◽  
Gynecological Malignancy ◽  
Serous Ovarian Carcinoma

AbstractHigh-grade serous ovarian carcinoma (HGSOC) is the most aggressive gynecological malignancy, resulting in approximately 70% of ovarian cancer deaths. However, it is still unclear how genetic dysregulations and biological processes generate the malignant subtype of HGSOC. Here we show that expression levels of microtubule affinity-regulating kinase 3 (MARK3) are downregulated in HGSOC, and that its downregulation significantly correlates with poor prognosis in HGSOC patients. MARK3 overexpression suppresses cell proliferation and angiogenesis of ovarian cancer cells. The LKB1-MARK3 axis is activated by metabolic stress, which leads to the phosphorylation of CDC25B and CDC25C, followed by induction of G2/M phase arrest. RNA-seq and ATAC-seq analyses indicate that MARK3 attenuates cell cycle progression and angiogenesis partly through downregulation of AP-1 and Hippo signaling target genes. The synthetic lethal therapy using metabolic stress inducers may be a promising therapeutic choice to treat the LKB1-MARK3 axis-dysregulated HGSOCs.

scholarly journals Dynamic changes in the urine proteome in two ovarian cancer rat models

2019 ◽  
Author(s):  
Yuqiu Li ◽  
Linpei Zhang ◽  
Wenshu Meng ◽  
Youhe Gao
Keyword(s):  
Ovarian Cancer ◽  
Early Detection ◽  
Cancer Progression ◽  
The Body ◽  
Cancer Development ◽  
Ovarian Cancer Cells ◽  
Rat Models ◽  
Gynecological Malignancy ◽  
Injection Model ◽  
Differential Proteins

AbstractOvarian cancer is the most lethal gynecological malignancy in women, and it is likely to metastasize and has a poor prognosis. The early and reliable diagnosis and monitoring of ovarian cancer is very important. Without a homeostasis mechanism, urine can reflect early systemic changes in the body and has a great potential to be used for the early detection of cancer. This study tested whether early changes could be detected in two ovarian cancer rat models. Two rat models were established by either intraperitoneal (i.p.) or orthotopic (o.t.) injection of NuTu-19 ovarian cancer cells in female Fischer344 rats. Urine samples from ovarian cancer rats were collected at five time points during cancer development, and urinary proteins from the rats were profiled by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Compared with pre-injection samples, 49 differential proteins that have human orthologues were significantly changed in the orthotopically injected model. Among them, 24 of the differential proteins have previously been reported to be associated with ovarian cancer, six of which were reported to be biomarkers of ovarian cancer. On the 7th day after orthotopic injection, four differential proteins (APOA1, OX2G, CHMP5, HEXB) were identified before obvious metastases appeared. In the intraperitoneal injection model, 76 differential proteins were changed during the course of ovarian cancer development. The results show that urine proteins could enable the early detection and monitoring of ovarian cancer progression and could lay a foundation for further exploration of the biomarkers of ovarian cancer.

Circular RNA hsa_circ_0078607 suppresses ovarian cancer progression by regulating miR-518a-5p/Fas signaling pathway

2020 ◽  
Author(s):  
Nan Zhang ◽  
Yue Jin ◽  
Qiubo Hu ◽  
Shanshan Cheng ◽  
Chao Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Malignant Tumors ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Ovarian Cancer Cells ◽  
Cancer Pathogenesis ◽  
Direct Target

Abstract Background: Increasing researches have demonstrated the critical functions of circular RNAs (circRNAs) in the progression of malignant tumors, including ovarian cancer. In this study, we aim to investigate abnormally expression of hsa_circ_0078607 and the role of hsa_circ_0078607 during ovarian cancer pathogenesis.Methods: RT-PCR were used to detect the expression of circ_0078607 in ovarian cancer tissues. To determine the functional roles of circ_0078607 in ovarian cancer, cell proliferation and cell invasion assays were performed. Bioinformatics and luciferase reporter analysis were used to predict the target of circ_0078607.Results: In the present study, we first found that circ_0078607 was downregulated in ovarian cancer. Forced circ_0078607 expression significantly suppressed proliferation and promotes apoptosis of ovarian cancer cells. Mechanically, bioinformatics and luciferase reporter analysis identified that miR-518a-5p as a direct target of circ_0078607, while Fas as a direct target of miR-518a-5p. MiR-518a-5p negatively regulates Fas in ovarian cancer cells, while overexpression of circ_0078607 could increase the expression of Fas inhibited by miR-518a-5p. Furthermore, overexpression of circ_0078607 could inhibit the proliferation and invasion of ovarian cancer cells caused by miR-518a-5p mimic.Conclusion: The results of the present study revealed that circ_0078607 suppresses ovarian cancer progression by sponging oncogenic miR-518a-5p to induce Fas expression, which may provide new therapeutic approach for ovarian cancer.

scholarly journals Promotion of Cell Death in Cisplatin-Resistant Ovarian Cancer Cells through KDM1B-DCLRE1B Modulation

2019 ◽  
Vol 20 (10) ◽  
pp. 2443 ◽  
Author(s):  
Yeon Kyu Lee ◽  
Jinyeong Lim ◽  
So Young Yoon ◽  
Jong Cheon Joo ◽  
Soo Jung Park ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Ovarian Cancer Cells ◽  
Repair Gene ◽  
Gynecological Malignancy ◽  
Downstream Target ◽  
Dna Repair Gene ◽  
Cisplatin Sensitivity

Ovarian cancer is the gynecological malignancy with the poorest prognosis, in part due to its high incidence of recurrence. Platinum agents are widely used as a first-line treatment against ovarian cancer. Recurrent tumors, however, frequently demonstrate acquired chemo-resistance to platinum agent toxicity. To improve chemo-sensitivity, combination chemotherapy regimens have been investigated. This study examined anti-tumor effects and molecular mechanisms of cytotoxicity of Oldenlandia diffusa (OD) extracts on ovarian cancer cells, in particular, cells resistant to cisplatin. Six ovarian cancer cells including A2780 and cisplatin-resistant A2780 (A2780cis) as representative cell models were used. OD was extracted with water (WOD) or 50% methanol (MOD). MOD significantly induced cell death in both cisplatin-sensitive cells and cisplatin-resistant cells. The combination treatment of MOD with cisplatin reduced viability in A2780cis cells more effectively than treatment with cisplatin alone. MOD in A2780cis cells resulted in downregulation of the epigenetic modulator KDM1B and the DNA repair gene DCLRE1B. Transcriptional suppression of KDM1B and DCLRE1B induced cisplatin sensitivity. Knockdown of KDM1B led to downregulation of DCLRE1B expression, suggesting that DCLRE1B was a KDM1B downstream target. Taken together, OD extract effectively promoted cell death in cisplatin-resistant ovarian cancer cells under cisplatin treatment through modulating KDM1B and DCLRE1B.

scholarly journals Platelet-activating factor acetyl hydrolase IB2 dysregulated cell proliferation in ovarian cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
YingYing He ◽  
Zhicheng He ◽  
Xiaoyu Zhang ◽  
Shubai Liu
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Platelet Activating Factor ◽  
Regulatory Subunit ◽  
Ovarian Cancer Cells ◽  
Cancer Tissue ◽  
Serine Esterase ◽  
Cancer Pathogenesis ◽  
The Impact

Abstract Background Ovarian cancer is the leading cause of death from gynaecologic illnessed worldwide. Platelet-activating factor acetyl hydrolase IB2 (PAF-AH IB2) is an intracellular serine esterase that hydrolyzes platelet-activating factor, a G-protein-like trimer with two catalytic subunits and one regulatory subunit. The regulatory role of PAF-AH IB2 in the oncogenesis of ovarian cancer is not well understood. Methods In this study, the TCGA dataset and clinical cancer tissue microarray were utilized to investigate abnormal overexpression of PAF-AH IB2 in ovarian cancer. To investigate the impact on the cell proliferation, migration, and tumorigenicity in vitro, PAF-AH IB2 stable knocking down (KD) ovarian cancer cells were established by ShRNA. The whole transcription profiling, tyrosine kinase profiling and standard cell functional assays were integrated to explore the biological importance and mechanism of PAF-AH IB2 modulated in ovarian cancer. Results PAF-AH IB2 was identified significantly overexpression in four subtypes of ovarian cancer. In vitro, PAF-AH IB2 KD significantly inhibited cancer cell proliferation, migration, and tumorigenicity, activated caspases and caused cell cycle arrest, and made the cells more sensitive to PAF. PAF-AH 1B2 KD cells down-regulated several key regulators of the multiple tyrosine kinases-mediated signaling pathway, suggesting a novel interaction network between the growth factor receptors pathway and PAF-AH 1B2 mediated PAF signalling. Conclusions These findings revealed a previously undiscovered role for PAF-AH IB2 as a potenial therapy target and essential signaling mediators in ovarian cancer pathogenesis, as well as new possible preventive and therapeutic strategies to inhibit this enzyme in clinical treatment for ovarian cancer.

scholarly journals Cellular and molecular processes in ovarian cancer metastasis. A Review in the Theme: Cell and Molecular Processes in Cancer Metastasis

2015 ◽  
Vol 309 (7) ◽  
pp. C444-C456 ◽  
Author(s):  
Tsz-Lun Yeung ◽  
Cecilia S. Leung ◽  
Kay-Pong Yip ◽  
Chi Lam Au Yeung ◽  
Stephen T. C. Wong ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Survival Rate ◽  
Cancer Cells ◽  
Primary Tumor ◽  
Cancer Metastasis ◽  
Hematogenous Metastasis ◽  
Ovarian Cancer Cells ◽  
Molecular Processes ◽  
Lower Survival Rate ◽  
Gynecological Malignancy

Ovarian cancer is the most lethal gynecological malignancy. It is usually diagnosed at a late stage, with a 5-yr survival rate of <30%. The majority of ovarian cancer cases are diagnosed after tumors have widely spread within the peritoneal cavity, limiting the effectiveness of debulking surgery and chemotherapy. Owing to a substantially lower survival rate at late stages of disease than at earlier stages, the major cause of ovarian cancer deaths is believed to be therapy-resistant metastasis. Although metastasis plays a crucial role in promoting ovarian tumor progression and decreasing patient survival rates, the underlying mechanisms of ovarian cancer spread have yet to be thoroughly explored. For many years, researchers have believed that ovarian cancer metastasizes via a passive mechanism by which ovarian cancer cells are shed from the primary tumor and carried by the physiological movement of peritoneal fluid to the peritoneum and omentum. However, the recent discovery of hematogenous metastasis of ovarian cancer to the omentum via circulating tumor cells instigated rethinking of the mode of ovarian cancer metastasis and the importance of the “seed-and-soil” hypothesis for ovarian cancer metastasis. In this review we discuss the possible mechanisms by which ovarian cancer cells metastasize from the primary tumor to the omentum, the cross-talk signaling events between ovarian cancer cells and various stromal cells that play crucial roles in ovarian cancer metastasis, and the possible clinical implications of these findings in the management of this deadly, highly metastatic disease.

Adipose-derived stem cells in ovarian cancer progression, metastasis, and chemoresistance

2021 ◽  
pp. 153537022110238
Author(s):  
Wenjing Zhang ◽  
Carolina Torres-Rojas ◽  
Junming Yue ◽  
Bing-Mei Zhu
Keyword(s):  
Ovarian Cancer ◽  
Stem Cell ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Early Stage ◽  
Ovarian Cancer Cells ◽  
High Recurrence Rate ◽  
Gynecological Malignancy ◽  
Adipose Derived Stem Cell

Ovarian cancer is the deadliest gynecological malignancy due to its symptomless early stage, metastasis, and high recurrence rate. The tumor microenvironment contributes to the ovarian cancer progression, metastasis, and chemoresistance. Adipose-derived stem cell in the tumor microenvironment of ovarian cancer, as a key player, interacts with ovarian cancer cells to form the cancer-associated fibroblasts and cancer-associated adipocytes, and secretes soluble factors to activate tumor cell signaling, which can promote ovarian cancer metastasis and chemoresistance. We summarize in this review the recent progress in the studies of interactions between adipose-derived stem cell and ovarian cancer, thus, to provide some insight for ovarian cancer therapy through targeting adipose-derived stem cell.

scholarly journals DGAT1 Expression Promotes Ovarian Cancer Progression and Is Associated with Poor Prognosis

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Leilei Xia ◽  
Ye Wang ◽  
Shengyun Cai ◽  
Mingjuan Xu
Keyword(s):  
Ovarian Cancer ◽  
Tumor Growth ◽  
Cancer Progression ◽  
Poor Prognosis ◽  
Rapid Development ◽  
Lipid Synthesis ◽  
Cancer Staging ◽  
The Cancer Genome Atlas ◽  
Ovarian Cancer Cells ◽  
Gynecological Malignancy

Background. Ovarian cancer is the most fatal gynecological malignancy. Owing to its insidious onset, rapid development, and poor prognosis, ovarian cancer is the fifth most common cause of death in women. Although immunotherapy-related drugs, such as Olaparib, can alleviate ovarian cancer progression, there are no remarkable breakthroughs for its effective treatment. It is considered that the transformation of normal cells to cancerous ones involves “recoding” of certain metabolic pathways. Diacylglycerol O-acyltransferase 1 (DGAT1) can synthesize triglycerides by transferring acyl-CoA to diacylglycerol, which plays a key role in lipid synthesis. However, the role of DGAT1 in ovarian cancer is not yet elucidated. Materials and Methods. We analyzed the correlation between DGAT1 and ovarian cancer staging, grading, vascular invasion, and prognosis by collating the information of ovarian cancer specimens from The Cancer Genome Atlas (TCGA) database. Furthermore, the effects of DGAT1 expression on proliferation, migration, invasion, and tumor growth were studied using ovarian cancer cell lines. GSEA was used to analyze the KEGG pathways and biological function enriched because of DGAT1 expression in ovarian cancer. Results. The expression of DGAT1 was elevated in advanced ( p = 0.0432 ), poorly differentiated ( p = 0.0148 ), and vascular invaded ( p = 0.0002 ) ovarian cancer specimens. Prognosis among patients with high expression of DGAT1 was poor. After DGAT1 expression was interfered, proliferation, migration, invasion, colony forming, and tumor growth of ovarian cancer cells were inhibited. In addition, GSEA showed that DGAT1 may be involved in the immune process. Conclusion. DGAT1 expression is associated with the clinical phenotype of ovarian cancer. We suggest that DGAT1 has potential implications in the treatment of ovarian cancer.

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