scholarly journals Correlation of the Aryl Hydrocarbon Receptor with FSHR in Ovarian Cancer Patients

2019 ◽  
Vol 20 (12) ◽  
pp. 2862 ◽  
Author(s):  
Eileen Deuster ◽  
Doris Mayr ◽  
Anna Hester ◽  
Thomas Kolben ◽  
Christine Zeder-Göß ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Aryl Hydrocarbon Receptor ◽  
Cancer Patients ◽  
Functional Role ◽  
Clear Cell ◽  
Staining Intensity ◽  
Prognostic Impact ◽  
Histological Subtypes ◽  
Aryl Hydrocarbon ◽  
The Impact

Expression of the aryl hydrocarbon receptor (AhR) has been described in various tumor entities from different organs. However, its role in ovarian cancer has not been thoroughly investigated. We aimed to elucidate the prognostic impact of AhR, its correlation with the follicle-stimulating hormone receptor (FSHR), and their functional role in ovarian cancer. By immunohistochemistry, AhR staining was analyzed in a subset of 156 samples of ovarian cancer patients. AhR staining was assessed in the nucleus and the cytoplasm using the semi-quantitative immunoreactive score (IRS), and the scores were grouped into high- and low-level expression. AhR expression was detected in all histological subtypes, with clear cell ovarian cancer displaying the highest staining intensity. Low cytoplasmic expression of AhR was associated with longer overall survival (median 183.46 vs. 85.07 months; p = 0.021). We found a positive correlation between AhR and FSHR (p = 0.005). Ovarian cancer patients with high cytoplasmic AhR and concurrent FSHR expression had the worst outcome (median 69.72 vs. 43.32 months; p = 0.043). Consequently, low cytoplasmic AhR expression seems to be associated with improved survival in ovarian cancer patients. Our data suggest that AhR and FSHR levels correlate with each other, and their concurrent expression was observed in ovarian cancer patients with the worst outcome. Further investigation of the interaction of both receptors and their functional role might better predict the impact of endocrine therapy in ovarian cancer.

scholarly journals Sarcopenic Factors May Have No Impact on Outcomes in Ovarian Cancer Patients

Diagnostics ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 206 ◽  
Author(s):  
Naomi Nakayama ◽  
Kentaro Nakayama ◽  
Kohei Nakamura ◽  
Sultana Razia ◽  
Satoru Kyo
Keyword(s):  
Ovarian Cancer ◽  
Skeletal Muscle ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Muscle Volume ◽  
Muscle Quality ◽  
Prognostic Impact ◽  
Poor Prognostic Factor ◽  
Skeletal Muscle Index ◽  
The Impact

Although the prognostic value of sarcopenic factors, such as loss of muscle mass and quality, have been widely reported in patients with cancer during the last decade, the value in those with ovarian cancer remains unclear. Therefore, this study evaluated the prognostic impact of sarcopenic factors in patients with ovarian cancer. We retrospectively evaluated the data of 94 ovarian cancer patients who underwent surgery and chemotherapy at the Shimane University Hospital between March 2006 and 2013. Preoperative computed tomography scan at the level of the third lumbar vertebra was used to evaluate skeletal muscle volume and quality based on the skeletal muscle index (SMI) and intramuscular adipose tissue content (IMAC), respectively. The impact of preoperative SMI and IMAC on outcomes was subsequently investigated. Low SMI and high IMAC were not significantly associated with disease-free survival (p = 0.329 and p = 0.3370, respectively) or poor overall survival (p = 0.921 and p = 0.988, respectively). Neither preoperative low muscle volume nor low muscle quality was a poor prognostic factor in ovarian cancer.

Significance of changes in serum CA125 level on overall survival in ovarian cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16546-e16546
Author(s):  
S. Williams ◽  
D. Gupta ◽  
S. Dahlk ◽  
K. E. Dzike ◽  
G. M. Lambert ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Case Series ◽  
Stage Iv ◽  
Time Interval ◽  
Prognostic Impact ◽  
Baseline Serum ◽  
Serum Ca125 ◽  
The Impact

e16546 Background: The role of baseline serum CA125 as a prognostic indicator in ovarian cancer is well documented. However, little is known about the impact of change in CA125 on survival after 3 months of therapy. We conducted survival analysis to answer the question “what is the prognostic impact of change in serum CA125 after 3 months of therapy in ovarian cancer?” Methods: A case series of 170 ovarian cancer patients treated at Cancer Treatment Centers of America between Jan 01 and May 06. Based on CA125 levels at baseline and 3 months, patients were classified into 4 groups: 1) Normal (0–35U/ml) at baseline and three months; 2) High (>35U/ml) at baseline, normal at three months; 3) Normal at baseline, high at 3 months; 4) High at baseline and three months. Kaplan Meier method was used to calculate survival across the 4 categories, which was defined as the time interval between date of patient visit at 3 months from first visit and date of death from any cause or date of last contact. Results: Of 170 patients, 36 were newly diagnosed while 134 had received prior treatment. 25 had stage I disease at diagnosis, 15 stage II, 106 stage III and 14 stage IV. The median age at presentation was 54.2 years (range 23.1 - 82.5 years). At baseline, 31 patients had normal (0–35U/ml) serum CA125 levels while 138 had high (>35U/ml) levels. At 3 months, 59 had normal while 111 had high levels. In this cohort, patients with a reduced CA125 at 3 months (stratum 2) had a significantly better survival than those with increased CA125 at 3 months (stratum 3). Patients with normal values of CA125 at both baseline and 3 months (stratum 1) had the best overall survival. Conclusions: These data show that reduction in CA125 after 3 months of therapy is associated with better overall survival in ovarian cancer. Patients without a significant decline in CA125 after 3 months of therapy have a particularly poor prognosis. [Table: see text] No significant financial relationships to disclose.

scholarly journals The Prognostic Impact of Intratumoral Aryl Hydrocarbon Receptor in Primary Breast Cancer Depends on the Type of Endocrine Therapy: A Population-Based Cohort Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Helga Tryggvadottir ◽  
Emma Sandén ◽  
Sofie Björner ◽  
Alessandra Bressan ◽  
Maria Ygland Rödström ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Aryl Hydrocarbon Receptor ◽  
Cancer Patients ◽  
Clinicopathological Features ◽  
Prognostic Impact ◽  
Recurrence Free Survival ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Aryl Hydrocarbon

The aryl hydrocarbon receptor (AhR) is a master regulator of multiple pathways involved in breast cancer, and influences the estrogen receptor alpha (ER) and aromatase/CYP19A1. The purpose of this study was to elucidate the interplay between intratumoral levels of AhR and aromatase, patient characteristics (including AhR and CYP19A1 genotypes), clinicopathological features, and prognosis in breast cancer patients receiving adjuvant treatments. A prospective cohort of 1116 patients with primary breast cancer in Sweden, included 2002–2012, was followed until June 30th 2019 (median 8.7 years). Tumor‐specific AhR (n=920) and aromatase levels (n=816) were evaluated on tissue microarrays using immunohistochemistry. Associations between cytoplasmatic (AhRcyt) and nuclear (AhRnuc) AhR levels, intratumoral aromatase, clinicopathological features, and prognosis in different treatment groups were analyzed. Low AhRcyt levels (n=183) and positive intratumoral aromatase (n=69) were associated with estrogen receptor (ER)– status and more aggressive tumors. Genotypes were not associated with their respective protein levels. The functional AhRArg554Lys GG genotype was associated with recurrence-free survival in switch-therapy (sequential tamoxifen/aromatase inhibitors (AI) or AI/tamoxifen) treated patients (HRadj 0.42; 95% CI 0.22–0.83). High AhRcyt levels were associated with longer recurrence-free survival during the first 10 years of follow-up among tamoxifen-only treated patients (HRadj 0.40; 95% CI 0.23–0.71) compared to low AhRcyt levels, whereas an almost inverse association was seen in patients with switch-therapy (Pinteraction=0.023). Intratumoral aromatase had little prognostic impact. These findings warrant confirmation in an independent cohort, preferably in a randomized clinical trial comparing different endocrine regimens. They might also guide the selection of breast cancer patients for clinical trials with selective AhR modulators.

scholarly journals Ovarian Endometrioid Carcinoma and Clear Cell Carcinoma: A 21-year Retrospective Study

2020 ◽  
Author(s):  
Ling Zhou ◽  
Liqing Yao ◽  
Lin Dai ◽  
Honglan Zhu ◽  
Xue Ye ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Carcinoma ◽  
Cancer Patients ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Clinicopathological Characteristics ◽  
Receptor Expression ◽  
Chinese Patients ◽  
Endometrioid Carcinoma ◽  
The Impact

Abstract ObjectiveThis study aimed to identify the clinical characteristics of Chinese patients with ovarian endometrioid carcinoma (EC) and clear cell carcinoma (CCC) and to assess the impact of concurrent endometriosis on this group.MethodsThe present study reviewed the medical records of patients who received initial treatment and a postoperative pathological diagnosis of EC or CCC at our center in China between 1998 and 2018. ResultsOf 211 patients, 73 had pure EC, and 91 had pure CCC, and the remaining 47 had mixed cancer. The proportion of EC and CCC remained stable over past 21 years. The proportion of EC declined with aging and the age of EC onset to incline to the young. And the age of CCC onset had two peaks, namely, 36 and 77 years. After review by the pathologist, the number of endometriosis cases found in the pathological section of the analysis increased to 114, accounting for 54% of patients. As the stage progressed, the appearance of endometriosis became increasingly scarce in pathological sections(p=0.001). Compared with CCC, EC had a higher frequency of concurrent endometrial cancer (independent endometrial lesions) and estrogen and progesterone receptor expression(p=0.000). And more patients were in premenopausal state in EC group(p=0.040). In the pure group, multivariate analysis showed that correlation existed between relevance to endometriosis and worse outcomes(p=0.041). In patients with mixed cancer, mixed endometrioid histology was associated with better survival than other subtypes, even with stage III or poorly differentiated tumors(p=0.001). ConclusionsCCC and EC which are common in ovarian cancer patients who have associated with endometriosis have distinct clinicopathological characteristics. Attention should be paid to ovarian cancer patients with a history of endometriosis and those with concurrent endometriosis in pathological sections.

scholarly journals Ovarian endometrioid carcinoma and clear cell carcinoma: A 21-year retrospective study

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Ling Zhou ◽  
Liqing Yao ◽  
Lin Dai ◽  
Honglan Zhu ◽  
Xue Ye ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Carcinoma ◽  
Cancer Patients ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Clinicopathological Characteristics ◽  
Receptor Expression ◽  
Chinese Patients ◽  
Endometrioid Carcinoma ◽  
The Impact

Abstract Objective This study aimed to identify the clinical characteristics of Chinese patients with ovarian endometrioid carcinoma (EC) and clear cell carcinoma (CCC) and to assess the impact of concurrent endometriosis on this group. Methods The present study reviewed the medical records of patients who received initial treatment and a postoperative pathological diagnosis of EC or CCC at our center in China between 1998 and 2018. Results Of 211 patients, 73 had pure EC, and 91 had pure CCC, and the remaining 47 had mixed cancer. The proportion of EC and CCC remained stable over past 21 years. The proportion of EC declined with aging and the age of EC onset to incline to the young. And the age of CCC onset had two peaks, namely, 36 and 77 years. After review by the pathologist, the number of endometriosis cases found in the pathological section of the analysis increased to 114, accounting for 54% of patients. As the stage progressed, the appearance of endometriosis became increasingly scarce in pathological sections(p = 0.001). Compared with CCC, EC had a higher frequency of concurrent endometrial cancer (independent endometrial lesions) and estrogen and progesterone receptor expression(p = 0.000). And more patients were in premenopausal state in EC group(p = 0.040). In the pure group, multivariate analysis showed that correlation existed between relevance to endometriosis and worse outcomes(p = 0.041). In patients with mixed cancer, mixed endometrioid histology was associated with better survival than other subtypes, even with stage III or poorly differentiated tumors(p = 0.001). Conclusions CCC and EC which are common in ovarian cancer patients who have associated with endometriosis have distinct clinicopathological characteristics. Attention should be paid to ovarian cancer patients with a history of endometriosis and those with concurrent endometriosis in pathological sections.

scholarly journals Characterizing the Role of HMG-CoA Reductase in Aryl Hydrocarbon Receptor-Mediated Liver Injury in C57BL/6 Mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Peter Dornbos ◽  
Amanda Jurgelewicz ◽  
Kelly A. Fader ◽  
Kurt Williams ◽  
Timothy R. Zacharewski ◽  
...  
Keyword(s):  
Liver Injury ◽  
Aryl Hydrocarbon Receptor ◽  
Cholesterol Biosynthesis ◽  
Competitive Inhibitor ◽  
Cholesterol Homeostasis ◽  
Hepatic Glycogen ◽  
Alcoholic Fatty Liver ◽  
Female Mice ◽  
Aryl Hydrocarbon ◽  
The Impact

Abstract The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor. The prototypical ligand of the AHR is an environmental contaminant called 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD exposure is associated with many adverse health outcomes in humans including non-alcoholic fatty liver disease (NAFLD). Previous studies suggest that AHR ligands alter cholesterol homeostasis in mice through repression of genes involved in cholesterol biosynthesis, such as Hmgcr, which encodes the rate-limiting enzyme of cholesterol biosynthesis called 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR). In this study, we sought to characterize the impact of HMGCR repression in TCDD-induced liver injury. C57BL/6 mice were exposed to TCDD in the presence or absence of simvastatin, a competitive inhibitor of HMGCR. Simvastatin exposure decreased TCDD-induced hepatic lipid accumulation in both sexes, but was most prominent in females. Simvastatin and TCDD (S + T) co-treatment increased hepatic AHR-battery gene expression and liver injury in male, but not female, mice. In addition, the S + T co-treatment led to an increase in hepatic glycogen content that coincides with heavier liver in female mice. Results from this study suggest that statins, which are amongst the most prescribed pharmaceuticals, may protect from AHR-mediated steatosis, but alter glycogen metabolism and increase the risk of TCDD-elicited liver damage in a sex-specific manner.

G-8 Geriatric Screening Tool Independently Predicts Progression-Free Survival in Older Ovarian Cancer Patients Irrespective of Maximal Surgical Effort: Results of a Retrospective Cohort Study

Gerontology ◽  
2021 ◽  
pp. 1-10
Author(s):  
Katharina Anic ◽  
Sophie Birkert ◽  
Mona Wanda Schmidt ◽  
Valerie Catherine Linz ◽  
Anne-Sophie Heimes ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Global Health ◽  
Screening Tool ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
Assessment Tools ◽  
Prognostic Impact ◽  
Free Survival ◽  
Geriatric Screening ◽  
The Impact

<b><i>Background:</i></b> We evaluated the prognostic impact of various global health assessment tools in patients older than 60 years with ovarian cancer (OC). <b><i>Methods:</i></b> G-8 geriatric screening tool (G-8 score), Lee Schonberg prognostic index, Eastern Cooperative Oncology Group (ECOG) performance status, and Charlson Comorbidity Index (CCI) were determined retrospectively in a consecutive cohort of elderly patients with OC. Univariate and multivariate Cox regression analyses and Kaplan-Meier method were performed to analyze the impact of the preoperative global health status on survival. <b><i>Results:</i></b> 116 patients entered the study. In multivariate analysis adjusted for clinical-pathological factors, only the G-8 score retained significance as a prognostic parameter of progression-free survival (PFS) (hazard ratio [HR]: 1.970; 95% confidence interval [CI] [1.056–3.677]; <i>p</i> = 0.033). Fifty-six patients were classified as G-8-nonfrail with an increased PFS compared to 50 G-8-frail patients (53.4% vs. 16.7%; <i>p</i> = 0.010). A higher CCI was associated with decreased PFS (45.1% vs. 22.2%; <i>p</i> = 0.012), but it did not influence the risk of recurrences or death (<i>p</i> = 0.360; <i>p</i> = 0.111). The Lee Schonberg prognostic index, the ECOG, and age were not associated with survival. <b><i>Conclusions:</i></b> The G-8 score independently predicted PFS in elderly OC patients regardless of maximal surgical effort. Thus, it could be useful to assess surgical treatment based on frailty rather than age alone.

scholarly journals Immunotoxicity of Xenobiotics in Fish: A Role for the Aryl Hydrocarbon Receptor (AhR)?

2021 ◽  
Vol 22 (17) ◽  
pp. 9460
Author(s):  
Helmut Segner ◽  
Christyn Bailey ◽  
Carolina Tafalla ◽  
Jun Bo
Keyword(s):  
Immune System ◽  
Aryl Hydrocarbon Receptor ◽  
Disease Susceptibility ◽  
Immune Cell ◽  
Physiological Role ◽  
Immune Gene ◽  
Immune Systems ◽  
Aryl Hydrocarbon ◽  
The Impact

The impact of anthropogenic contaminants on the immune system of fishes is an issue of growing concern. An important xenobiotic receptor that mediates effects of chemicals, such as halogenated aromatic hydrocarbons (HAHs) and polyaromatic hydrocarbons (PAHs), is the aryl hydrocarbon receptor (AhR). Fish toxicological research has focused on the role of this receptor in xenobiotic biotransformation as well as in causing developmental, cardiac, and reproductive toxicity. However, biomedical research has unraveled an important physiological role of the AhR in the immune system, what suggests that this receptor could be involved in immunotoxic effects of environmental contaminants. The aims of the present review are to critically discuss the available knowledge on (i) the expression and possible function of the AhR in the immune systems of teleost fishes; and (ii) the impact of AhR-activating xenobiotics on the immune systems of fish at the levels of immune gene expression, immune cell proliferation and immune cell function, immune pathology, and resistance to infectious disease. The existing information indicates that the AhR is expressed in the fish immune system, but currently, we have little understanding of its physiological role. Exposure to AhR-activating contaminants results in the modulation of numerous immune structural and functional parameters of fish. Despite the diversity of fish species studied and the experimental conditions investigated, the published findings rather uniformly point to immunosuppressive actions of xenobiotic AhR ligands in fish. These effects are often associated with increased disease susceptibility. The fact that fish populations from HAH- and PAH-contaminated environments suffer immune disturbances and elevated disease susceptibility highlights that the immunotoxic effects of AhR-activating xenobiotics bear environmental relevance.

scholarly journals Increase Paclitaxel Sensitivity to Better Suppress Serous Epithelial Ovarian Cancer via Ablating Androgen Receptor/Aryl Hydrocarbon Receptor-ABCG2 Axis

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 463 ◽  
Author(s):  
Wei-Min Chung ◽  
Yen-Ping Ho ◽  
Wei-Chun Chang ◽  
Yuan-Chang Dai ◽  
Lumin Chen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Androgen Receptor ◽  
Epithelial Ovarian Cancer ◽  
Aryl Hydrocarbon Receptor ◽  
Proximal Promoter ◽  
Luciferase Reporter ◽  
Aryl Hydrocarbon ◽  
Paclitaxel Treatment

Background: Epithelial ovarian cancer (EOC) is one of the most lethal gynecological malignancies and presents chemoresistance after chemotherapy treatment. Androgen receptor (AR) has been known to participate in proliferation. Yet the mechanisms of the resistance of this drug and its linkage to the AR remains unclear. Methods: To elucidate AR-related paclitaxel sensitivity, co-IP, luciferase reporter assay and ChIP assay were performed to identify that AR direct-regulated ABCG2 expression under paclitaxel treatment. IHC staining by AR antibody presented higher AR expression in serous-type patients than other types. AR degradation enhancer (ASC-J9) was used to examine paclitaxel-associated and paclitaxel-resistant cytotoxicity in vitro and in vivo. Results: We found AR/aryl hydrocarbon receptor (AhR)-mediates ABCG2 expression and leads to a change in paclitaxel cytotoxicity/sensitivity in EOC serous subtype cell lines. Molecular mechanism study showed that paclitaxel activated AR transactivity and bound to alternative ARE in the ABCG2 proximal promoter region. To identify AR as a potential therapeutic target, the ASC-J9 was used to re-sensitize paclitaxel-resistant EOC tumors upon paclitaxel treatment in vitro and in vivo. Conclusion: The results demonstrated that activation of AR transactivity beyond the androgen-associated biological effect. This novel AR mechanism explains that degradation of AR is the most effective therapeutic strategy for treating AR-positive EOC serous subtype.

scholarly journals Prognostic impact of CA15-3 pre-treatment levels in ovarian cancer patients

2017 ◽  
Vol 28 ◽  
pp. vi71-vi72
Author(s):  
E. Maccaroni ◽  
R. Giampieri ◽  
M. Del Prete ◽  
G. Principi ◽  
R. Bracci ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Prognostic Impact ◽  
Pre Treatment
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