Expression of Catechol O methyl transferase (COMT) with the contrasting effects of 17β estradiol (E2): Implications for the mechanism of estrogen-induced ovarian carcinogenesis.

2020 ◽  
Author(s):  
Nour Mohamed El-Etreby ◽  
Eman Medhat Osman ◽  
Nehal Abd El Latif El Badawy ◽  
Hoda Abd El Hamid Nour

Abstract Background Epidemiological data show that induction of ovarian cancer is related to estrogen exposure and metabolism. In addition catechol metabolites of estrogen also contribute to carcinogenesis. O methylation by Catechol O methyl transferase (COMT) is a phase II metabolic inactivation pathway for catechol estrogens. The goal of the present study was to investigate the role of COMT level in ovarian carcinogenesis with the contrasting effects of 17 β estradiol level. Subjects and methods Our study was conducted on 80 subjects divided into 30 patients with malignant ovarian tumors ,30 patients with benign ovarian tumors and 20 healthy controls. Tissue and serum levels of COMT and 17 17 β estradiol were determined using ELISA Results According to our results COMT inhibition in the malignant group was detected as high as 7.1 pmol/L E2 in serum and 15.6 pmol/L E2 in tissue homogenate. This inhibition was absent in the benign group as high as 7.53 pmol/L E2 in serum and as high as 14.9 pmol/L E2 in tissue homogenates. Conclusions Our results provide evidence for the protective effect of COMT in benign ovaries against neoplastic transformation. This supports the notion that targeting the metabolism of estrogen can be an another way to reduce ovarian cancer risk.

2015 ◽  
Vol 12 (2) ◽  
pp. 293-300
Author(s):  
Baghdad Science Journal

Epithelial ovarian cancer is the leading cause of cancer deaths from gynecological malignancies. Angiogenesis is considered essential for tumor growth and the development of metastases. VEGF and IL?8 are potent angiostimulatory molecules and their expression has been demonstrated in many solid tumors, including ovarian cancer.VEGF and IL-8 concentrations were measured by ELISA test (HumanVEGF,IL-8). Bioassay ELISA/ US Biological / USA).The median VEGF and IL-8 levels were significantly higher in the sera of ovarian cancer patients than in those with benign tumors and in healthy controls.Pretreatment VEGF and IL-8 serum levels might be regarded as an additional tool in the differentiation of ovarian tumors.


2020 ◽  
Vol 29 (11) ◽  
pp. 2211-2219
Author(s):  
Amy L. Shafrir ◽  
Ana Babic ◽  
Margaret Gates Kuliszewski ◽  
Megan S. Rice ◽  
Mary K. Townsend ◽  
...  

1998 ◽  
Vol 13 (3) ◽  
pp. 165-168 ◽  
Author(s):  
S. Krämer ◽  
M. Leeker ◽  
W. Jäger

Gonadotropins can stimulate ovarian cancer growth in cell cultures. Corresponding LH/hCG receptors have been demonstrated in ovarian cancer. However, reduction of elevated serum gonadotropins by GnRH analogs in ovarian cancer patients did not lead to growth restriction, which means that serum levels of gonadotropins may not play the most important role in ovarian cancer. We therefore analyzed the LH and FSH concentrations in cyst fluids of ovarian cancer. Patients with preoperatively diagnosed cystic ovarian tumors were eligible for the study. Serum samples of the patients were obtained during surgery, while the fluids within the cysts were aspirated after surgical removal of the tumor. FSH and LH levels in serum and cyst fluids were measured using single antibody EIA (Boehringer Mannheim GmbH, Germany). Cyst fluids and sera of 108 patients were evaluated. While there were no significant differences in the FSH and LH serum concentrations, highly significant differences in the FSH and LH levels in cyst fluids were found. Only cancer cysts contained FSH and LH, while the corresponding concentrations in benign cysts were always below the measuring range of the assays. This clear division between high gonadotropin levels in cysts of serous ovarian cancer and low or absent concentrations in benign ovarian tumors further supports the hypothesis that FSH and LH may play a role in ovarian cancer; however, explanations for this surprising finding are still lacking.


2004 ◽  
Vol 11 (2) ◽  
pp. 315-321 ◽  
Author(s):  
I Rzepka-G√≥rska ◽  
A Chudecka-G≈Çaz ◽  
B Kosmowska

The aim of this work was to compare mean concentrations of gonadotropins in serum and fluid from malignant and benign ovarian tumors. We enrolled 126 patients diagnosed with malignant epithelial tumors (n=40), borderline epithelial tumors (n=14), benign cystadenomas (n=28) and simple cysts (n=44) of the ovary. Premenopausal and postmenopausal subgroups were formed in each group. The concentration of FSH and LH was measured in serum and tumor fluid and the serum/tumor fluid ratio was calculated. The results in each group were compared and the sensitivity, specificity, positive and negative predictive values were determined. Mean concentrations of both gonadotropins in ovarian cancer fluid were significantly higher than in the remaining groups (P ranged from <0.005 to <0.0001). Mean serum/fluid ratios were lowest in ovarian cancer (FSH=2.91, LH=4.19). Our findings support the hypothesis that gonadotropins are involved in ovarian carcinogenesis and suggest that gonadotropin serum/tumor fluid ratios could be of value in the differential diagnosis of functional and organic cysts of the ovary.


2018 ◽  
Vol 3 (2) ◽  
pp. 20
Author(s):  
Modinat Jolade Adaranijo ◽  
Christian Bach

Ovarian cancer continues to be one of the deadliest and lethal form of gynecological cancer affecting younger and older woman. Understanding various factors that could lead to ovarian cancer and how they are able to drive its progression, metastasis and survival might help in its treatment and prevention. This paper aims to review different risk factors both genetic and environmental that could lead to the development of ovarian cancer and their mechanism of action. The research methods used in this study follows the principles outlined by [1]. It is a comprehensive literature review on ovarian cancer risk factor. The role of genetics and environmental risk factors in ovarian carcinogenesis and their mechanism of action created a theoretical foundation of the paper. A new model is presented to encapsulate highly dynamic interaction between ovarian carcinogenesis and the mechanism of action of some associated risk factors. The contribution of the study is intended to review and summarize the theoretical and empirical knowledge that should inspire new discussions and directions for further research activity. The model highlights various factors that can trigger the development of ovarian cancer namely; TP53, BRCA genes, Cigarette smoke and Talc powder and how they are able to promote ovarian cancer. Various have been done about how mutation of certain genes and some environmental factors could lead to ovarian carcinogenesis. However, more research is needed to further understand how their mechanism of action. The content of this paper will be useful in devising a better screening, treatment and preventive measure towards the ovarian cancer. This study provides an exciting opportunity to advance our knowledge of ovarian cancer to efficiently aid medical practitioners and researchers to device better prevention and treatment plan to combat ovarian cancer.


Author(s):  
Javier de la Torre Fernández de Vega ◽  
Jose Luis Sánchez-Iglesias ◽  
Assumpt Perez-Benavente ◽  
Antonio Gil-Moreno ◽  
Rasheda Begum Dina ◽  
...  

Epithelial ovarian cancer presents different histological subtypes, mainly serous, mucinous, endometriod, clear cell, mixed and undifferentiated cell. Molecular genetic studies have led to a new paradigm based on a dualistic model of ovarian carcinogenesis. There is a causal association between endometriosis and specific types of ovarian carcinomas, but the magnitude of the risk is low and endometriosis is not considered a premalignant lesion. Among the endometriosis-associated ovarian tumors adenocarcinoma is the most common (Endometrioid and clear cell) (70%), sarcoma is the second most common malignancy (12%) and rare cell types 6%. The gynecologist should pay special attention to identify patients with endometriosis who may be at an increased risk for ovarian cancer.


Author(s):  
Marek Nowak ◽  
Łukasz Janas ◽  
Malwina Soja ◽  
Ewa Głowacka ◽  
Krzysztof Szyłło ◽  
...  

IntroductionChemokines play a crucial role in tumor growth and progression according to proangiogenic and immunosuppressive acting. This study was aimed to investigate the serum levels of selected chemokines in patients with ovarian cancer or benign ovarian tumors to point on their role in tumorigenesis and their potential use in preoperative diagnosing of adnexal mass.Material and methodsThe study group consisted of 59 women with ovarian cancer: 17 epithelial ovarian cancer (EOC) patients and 42 women with benign ovarian tumors. We measured in sera obtained preoperatively the level of CA125 and the panel of 5 chemokines: CX3CL1/Fractalkine, CXCL1/GRO-α, CXCL12/SDF-1, CCL20/MIP-3α and IL-17F, using chemiluminescence method with multiplexed bead based immunoassay.ResultsCX3CL1 was significantly elevated in sera of advanced ovarian cancer patients compared to women with benign ovarian tumors. The significant elevation of CXCL1 was also observed (both: early and advanced stage). The similar pattern was present with standard ovarian cancer marker – CA125. In our patients with endometriotic cysts CA125 levels were significantly higher than in women with other benign tumors whereas all analyzed chemokines had similar serum titers in patients with endometriotic vs other benign ovarian cysts.ConclusionsCX3CL1 and CXCL1 are elevated in sera of EOC patients what points on their role in cancer development. Moreover, they might be useful in preoperative differential diagnosis of ovarian tumors, especially as they were not elevated in cases of endometriosis.


2021 ◽  
Vol 31 (3) ◽  
pp. 475-479
Author(s):  
Ekaterina Bunyaeva ◽  
Anastasia Kirillova ◽  
Grigory Khabas ◽  
Alexandra Asaturova ◽  
Nona Mishieva ◽  
...  

ObjectiveIn vitro maturation of oocytes collected from oophorectomy samples might be a promising approach in the field of oncofertility. In this study, we evaluate the feasibility of in vitro maturation of oocytes collected from oophorectomy samples in patients with ovarian tumors.MethodsThis prospective observational study included 27 patients with malignant ovarian tumors. Patients underwent oophorectomy and ovarian tissue was examined for the presence of immature cumulus-oocyte complexes. These were matured in vitro for 48 hours. Mature oocytes were vitrified or used for fertilization. Serum anti-müllerian hormone (AMH) levels were analyzed in 11 patients and cancer antigen 125 (CA125) levels in 16 patients.ResultsIn this study, 99 cumulus-oocyte complexes were obtained from 17 patients (63%). The mean (SE) age of the patients was 33.47±1.86 years (range 16–44). A total of 14 patients had ovarian cancer (IA–IVB), one patient had ovarian cancer IC and endometrial cancer IA, one patient had endometrial cancer stage IA with metastasis into the ovary, and one patient had cervical cancer stage IIB with metastasis in the ovary. Oocytes were not obtained in 10 patients who had diminished ovarian reserve due to age (>38 years), chemotherapy, or previous surgical treatment. On average, 5.8 cumulus-oocyte complexes were obtained per patient. The maturation rate was 40.4% with an average of 2.8 metaphase II oocytes per patient. As a result of the study, 3 blastocysts in 3 patients and 22 oocytes in 9 patients were vitrified.ConclusionsIn vitro maturation of oocytes collected from oophorectomy samples in patients with malignant ovarian tumors may result in oocyte and blastocyst vitrification. However, it should be offered to patients before surgery and chemotherapy. This method might be most beneficial in patients younger than 38 years, with AMH serum levels >1 ng/mL and without a large tumor burden.


Author(s):  
Mandy Spaan ◽  
Alexandra W van den Belt-Dusebout ◽  
Cornelis B Lambalk ◽  
Hester H van Boven ◽  
Roel Schats ◽  
...  

Abstract Background Long-term effects of assisted reproductive technology (ART) on ovarian tumor risk are unknown. Methods This nationwide cohort study comprises 30 625 women who received ovarian stimulation for ART in 1983-2000 and 9988 subfertile women not treated with ART. Incident invasive and borderline ovarian tumors were ascertained through linkage with the Netherlands Cancer Registry and the Dutch Pathology Registry until July 2018. Ovarian tumor risk in ART-treated women was compared with risks in the general population and the subfertile non-ART group. Statistical tests were 2-sided. Results After a median follow-up of 24 years, 158 invasive and 100 borderline ovarian tumors were observed. Ovarian cancer risk in the ART group was increased compared with the general population (standardized incidence ratio [SIR] = 1.43, 95% confidence interval [CI] = 1.18 to 1.71) but not when compared with the non-ART group (age- and parity-adjusted hazard ratio [HR] = 1.02, 95% CI = 0.70 to 1.50). Risk decreased with higher parity and with a larger number of successful ART cycles (resulting in childbirth, Ptrend = .001) but was not associated with the number of unsuccessful ART cycles. Borderline ovarian tumor risk was increased in ART-treated women compared with the general population (SIR = 2.20, 95% CI = 1.66 to 2.86) and with non-ART women (HR = 1.84, 95% CI = 1.08 to 3.14). Risk did not increase with more ART cycles or longer follow-up time. Conclusions Increased ovarian cancer risk in ART-treated women compared with the general population is likely explained by nulliparity rather than ART treatment. The increased risk of borderline ovarian tumors after ART must be interpreted with caution because no dose-response relationship was observed.


2015 ◽  
Vol 22 (6) ◽  
pp. R339-R363 ◽  
Author(s):  
Helen Gharwan ◽  
Kristen P Bunch ◽  
Christina M Annunziata

Epithelial ovarian cancer comprises ∼85% of all ovarian cancer cases. Despite acceptance regarding the influence of reproductive hormones on ovarian cancer risk and considerable advances in the understanding of epithelial ovarian carcinogenesis on a molecular level, complete understanding of the biologic processes underlying malignant transformation of ovarian surface epithelium is lacking. Various hypotheses have been proposed over the past several decades to explain the etiology of the disease. The role of reproductive hormones in epithelial ovarian carcinogenesis remains a key topic of research. Primary questions in the field of ovarian cancer biology center on its developmental cell of origin, the positive and negative effects of each class of hormones on ovarian cancer initiation and progression, and the role of the immune system in the ovarian cancer microenvironment. The development of the female reproductive tract is dictated by the hormonal milieu during embryogenesis. Intensive research efforts have revealed that ovarian cancer is a heterogenous disease that may develop from multiple extra-ovarian tissues, including both Müllerian (fallopian tubes, endometrium) and non-Müllerian structures (gastrointestinal tissue), contributing to its heterogeneity and distinct histologic subtypes. The mechanism underlying ovarian localization, however, remains unclear. Here, we discuss the role of reproductive hormones in influencing the immune system and tipping the balance against or in favor of developing ovarian cancer. We comment on animal models that are critical for experimentally validating existing hypotheses in key areas of endocrine research and useful for preclinical drug development. Finally, we address emerging therapeutic trends directed against ovarian cancer.


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