scholarly journals Expression Pattern of Leptin and Its Receptors in Endometrioid Endometrial Cancer

2021 ◽  
Vol 10 (13) ◽  
pp. 2787
Author(s):  
Dariusz Boroń ◽  
Robert Nowakowski ◽  
Beniamin Oskar Grabarek ◽  
Nikola Zmarzły ◽  
Marcin Opławski
Keyword(s):  
Endometrial Cancer ◽  
Cancer Treatment ◽  
Expression Profile ◽  
Whole Blood ◽  
Leptin Receptor ◽  
Treatment Strategies ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tissue Samples ◽  
Increased Risk ◽  
Risk Of Cancer

The identification of novel molecular markers and the development of cancer treatment strategies are very important as cancer incidence is still very high. Obesity can contribute to cancer progression, including endometrial cancer. Adipocytes secrete leptin, which, when at a high level, is associated with an increased risk of cancer. The aim of this study was to determine the expression profile of leptin-related genes in the endometrial tissue samples and whole blood of patients. The study material included tissue samples and whole blood collected from 30 patients with endometrial cancer and 30 without cancer. Microarrays were used to assess the expression profile of leptin-related genes. Then, the expression of leptin (LEP), leptin receptor (LEPR), leptin receptor overlapping transcript (LEPROT), and leptin receptor overlapping transcript-like 1 (LEPROTL1) was determined by the Real-Time Quantitative Reverse Transcription Reaction (RT-qPCR). The serum leptin concentration was evaluated using Enzyme-linked immunosorbent assay (ELISA). Leptin and its receptors were overexpressed both at the mRNA and protein levels. Furthermore, there were strong positive correlations between leptin levels and patient Body Mass Index (BMI). Elevated levels of leptin and its receptors may potentially contribute to the progression of endometrial cancer. These observations may be useful in designing endometrial cancer treatment strategies.

scholarly journals Bicuspid aortic valve patients show specific epigenetic tissue signature increasing extracellular matrix destruction

2019 ◽  
Vol 29 (6) ◽  
pp. 937-943 ◽  
Author(s):  
Josephina Haunschild ◽  
Isabel N Schellinger ◽  
Sarah J Barnard ◽  
Konstantin von Aspern ◽  
Piroze Davierwala ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Aortic Valve ◽  
Bicuspid Aortic Valve ◽  
Epigenetic Regulation ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Aortic Tissue ◽  
Tissue Inhibitor ◽  
Tissue Samples ◽  
Increased Risk

Abstract OBJECTIVES Patients with a bicuspid aortic valve (BAV) have an increased risk for developing thoracic aortic aneurysm, which is characterized by the destruction of the elastic media of the aortic wall. Several important enzymes have been characterized to play key roles in extracellular matrix homeostasis, namely matrix metalloproteinases (MMPs). In this study, we investigated MMP-2 levels and their epigenetic regulation via the miR-29 family. METHODS Aortic tissue samples from 58 patients were collected during cardiac surgery, of which 30 presented with a BAV and 28 with a tricuspid aortic valve. Polymerase chain reaction, western blot analysis and immunohistochemistry were performed to analyse MMP-2. In addition, enzyme-linked immunosorbent assay measurements were carried out to investigate both MMP-2 and tissue inhibitor of metalloproteinase-2 levels. To examine the epigenetic regulation of aortic extracellular matrix homeostasis, we furthermore studied the expression levels of miR-29 via qRT-PCR. RESULTS Patients with a BAV were significantly younger at the time of surgery, presented significantly less frequently with arterial hypertension and displayed more often with an additional valvular disease. On a molecular level, we found that MMP-2 is increased on gene and protein level in BAV patients. Tissue inhibitor of metalloproteinase-2 levels do not differ between the groups. Interestingly, we also found that only miR-29A is significantly downregulated in BAVs. CONCLUSIONS Our findings highlight the importance of MMP-2 in the context of extracellular matrix destruction in BAV patients. We present new evidence that miR-29A is a crucial epigenetic regulator of these pathomechanistic processes and might hold promise for future translational research.

scholarly journals Quantifying Microsatellite Mutation Rates from Intestinal Stem Cell Dynamics in Msh2-Deficient Murine Epithelium

Genetics ◽  
2019 ◽  
Vol 212 (3) ◽  
pp. 655-665 ◽  
Author(s):  
Joseph Christopher ◽  
Ann-Sofie Thorsen ◽  
Sam Abujudeh ◽  
Filipe C. Lourenço ◽  
Richard Kemp ◽  
...  
Keyword(s):  
Stem Cell ◽  
Fold Increase ◽  
Mutation Rates ◽  
Wild Type ◽  
Cell Dynamics ◽  
Tissue Samples ◽  
Age Related ◽  
Increased Risk ◽  
Microsatellite Mutation ◽  
Risk Of Cancer

Microsatellite sequences have an enhanced susceptibility to mutation, and can act as sentinels indicating elevated mutation rates and increased risk of cancer. The probability of mutant fixation within the intestinal epithelium is dictated by a combination of stem cell dynamics and mutation rate. Here, we exploit this relationship to infer microsatellite mutation rates. First a sensitive, multiplexed, and quantitative method for detecting somatic changes in microsatellite length was developed that allowed the parallel detection of mutant [CA]n sequences from hundreds of low-input tissue samples at up to 14 loci. The method was applied to colonic crypts in Mus musculus, and enabled detection of mutant subclones down to 20% of the cellularity of the crypt (∼50 of 250 cells). By quantifying age-related increases in clone frequencies for multiple loci, microsatellite mutation rates in wild-type and Msh2-deficient epithelium were established. An average 388-fold increase in mutation per mitosis rate was observed in Msh2-deficient epithelium (2.4 × 10−2) compared to wild-type epithelium (6.2 × 10−5).

scholarly journals Endometrial Cancer Patients: A Cohort Previous to Changes in Tumour Behaviour and Treatment Strategies

2011 ◽  
Vol 2011 ◽  
pp. 1-6
Author(s):  
F. K. L. Tournois ◽  
H. J. M. M. Mertens
Keyword(s):  
Endometrial Cancer ◽  
Cancer Treatment ◽  
Treatment Strategies ◽  
Patient Characteristics ◽  
National Guidelines ◽  
Treatment Regimens ◽  
Time Period ◽  
New Treatment ◽  
Figo Classification

Nowadays, the incidence of endometrial cancer is rising, especially of high-grade endometrial tumours. Recently, the FIGO classification of endometrial cancer has changed worldwide. Besides that, treatment strategies are changing. The purpose of this study was to analyse the adherence to the national guidelines of cancer treatment and to analyse patterns of disease relapse and survival. We focused on a group of patients () with endometrial cancer, in a time period in which new treatment strategies are not yet completely implemented. Because of multiple upcoming changes in patient characteristics, tumour classification, as well as treatment regimens, a more heterogeneous cohort of patients diagnosed with endometrial cancer will appear. From now on, all those changes will have their effects on the followup of conventional endometrial cancer treatment. In our opinion, it is, therefore, valuable to have the current, more homogenous, cohort clearly described.

scholarly journals Evaluation of the Differences in the Expression of Biogenic Amine-Related mRNAs and Proteins in Endometrioid Endometrial Cancer

2021 ◽  
Vol 10 (21) ◽  
pp. 4872
Author(s):  
Michał Czerwiński ◽  
Anna Bednarska-Czerwińska ◽  
Nikola Zmarzły ◽  
Dariusz Boroń ◽  
Marcin Oplawski ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Biogenic Amine ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Histamine H4 Receptor ◽  
Tissue Samples ◽  
Protein Levels ◽  
Endometrioid Endometrial Cancer ◽  
H4 Receptor ◽  
Dopamine D5 Receptor

Biogenic amines, such as adrenaline, noradrenaline, histamine, dopamine, and serotonin are important neurotransmitters that also regulate cell viability. Their detection and analysis are helpful in the diagnosis of many diseases, including cancer. The aim of this study was to determine the expression profile of the biogenic amine-related genes and proteins in endometrioid endometrial cancer compared to the control group. The material consisted of endometrial tissue samples and whole blood collected from 30 endometrioid endometrial cancer patients and 30 cancer-free patients. The gene expression was determined by the mRNA microarrays and validated by qRT-PCR. Protein levels were determined in the serum by the enzyme-linked immunosorbent assay (ELISA). Overexpression of histamine H1–H3 receptors and early growth response 1 and silencing of calmodulin, the histamine H4 receptor, and the dopamine D5 receptor have been reported in endometrioid endometrial cancer. The obtained results indicate disturbances in the signaling activated by histamine and dopamine receptors, which could potentially contribute to the progression of endometrioid endometrial cancer.

scholarly journals Profiling of Endogenous Estrogens, Their Precursors, and Metabolites in Endometrial Cancer Patients: Association with Risk and Relationship to Clinical Characteristics

Endocrinology ◽  
2011 ◽  
Vol 152 (1) ◽  
pp. 335-335
Author(s):  
Étienne Audet-Walsh ◽  
Johanie Lépine ◽  
Jean Grégoire ◽  
Marie Plante ◽  
Patrick Caron ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Postmenopausal Women ◽  
Clinical Characteristics ◽  
Estrogenic Activity ◽  
Low Grade ◽  
Type I ◽  
Healthy Women ◽  
Increased Risk ◽  
Risk Of Cancer ◽  
Circulating Levels

Background: Endometrial cancer (EC) predominantly occurs after menopause and is strongly related to steroid hormones, particularly estrogens. However, the relationship between these hormones and clinical characteristics remains unaddressed. Experimental Design: We analyzed the circulating levels of 18 steroids including adrenal precursors, androgens, estrogens, and their glucuronide metabolites, using specific and validated methods based on tandem mass spectrometry. Our goals were to compare circulating levels in postmenopausal women with EC (n = 126) with those of healthy postmenopausal women (n = 110) and to investigate how these hormonal levels relate to clinical characteristics. Results: After adjustment for potential confounders, most hormones were significantly elevated in EC patients compared with healthy controls. In women with type I cancer, estrogen levels were up to 3-fold those of healthy women (P < 0.05). These higher levels were associated with an increased risk of cancer, particularly estrogens and their direct precursors, testosterone and androstenedione (odds ratios ranging from 4.4 to 13.3; P ≤ 0.0003). Elevated circulating levels of estrogens and their metabolites were found in cancer cases with type I endometrioid cancer and low-grade and noninvasive tumor, suggesting an association between these hormones and the tumoral estrogenic activity. In addition, levels of estrone sulfate in EC patients with relapse were 2-fold over levels of EC patients without relapse (P < 0.05), and 4.5-fold over those of healthy women (P < 0.001). Conclusions: Circulating levels of steroids were associated with increased risk of EC. Estrogens may represent novel biomarkers predictive of clinical characteristics, including evidence for an increased risk of relapse.

scholarly journals Profiling of Endogenous Estrogens, Their Precursors, and Metabolites in Endometrial Cancer Patients: Association with Risk and Relationship to Clinical Characteristics

2011 ◽  
Vol 96 (2) ◽  
pp. E330-E339 ◽  
Author(s):  
Étienne Audet-Walsh ◽  
Johanie Lépine ◽  
Jean Grégoire ◽  
Marie Plante ◽  
Patrick Caron ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Postmenopausal Women ◽  
Clinical Characteristics ◽  
Estrogenic Activity ◽  
Low Grade ◽  
Type I ◽  
Healthy Women ◽  
Increased Risk ◽  
Risk Of Cancer ◽  
Circulating Levels

abstract Background: Endometrial cancer (EC) predominantly occurs after menopause and is strongly related to steroid hormones, particularly estrogens. However, the relationship between these hormones and clinical characteristics remains unaddressed. Experimental Design: We analyzed the circulating levels of 18 steroids including adrenal precursors, androgens, estrogens, and their glucuronide metabolites, using specific and validated methods based on tandem mass spectrometry. Our goals were to compare circulating levels in postmenopausal women with EC (n = 126) with those of healthy postmenopausal women (n = 110) and to investigate how these hormonal levels relate to clinical characteristics. Results: After adjustment for potential confounders, most hormones were significantly elevated in EC patients compared with healthy controls. In women with type I cancer, estrogen levels were up to 3-fold those of healthy women (P < 0.05). These higher levels were associated with an increased risk of cancer, particularly estrogens and their direct precursors, testosterone and androstenedione (odds ratios ranging from 4.4 to 13.3; P ≤ 0.0003). Elevated circulating levels of estrogens and their metabolites were found in cancer cases with type I endometrioid cancer and low-grade and noninvasive tumor, suggesting an association between these hormones and the tumoral estrogenic activity. In addition, levels of estrone-sulfate in EC patients with relapse were 2-fold over levels of EC patients without relapse (P < 0.05), and 4.5-fold over those of healthy women (P < 0.001). Conclusions: Circulating levels of steroids were associated with increased risk of EC. Estrogens may represent novel biomarkers predictive of clinical characteristics, including evidence for an increased risk of relapse.

scholarly journals Diet and risk of breast, endometrial and ovarian cancer: UK Women’s Cohort Study

2018 ◽  
Vol 122 (5) ◽  
pp. 564-574 ◽  
Author(s):  
Yashvee Dunneram ◽  
Darren C. Greenwood ◽  
Janet E. Cade
Keyword(s):  
Ovarian Cancer ◽  
Endometrial Cancer ◽  
Cohort Study ◽  
Postmenopausal Breast Cancer ◽  
Processed Meat ◽  
Food Groups ◽  
Dried Fruits ◽  
Increased Risk ◽  
Risk Of Cancer ◽  
Reduced Risk

AbstractThis study aimed to investigate the association between diet and the risk of breast, endometrial and ovarian cancer in the UK Women’s Cohort Study. A total of 35 372 women aged 35–69 years were enrolled between 1995 and 1998 and completed a validated 217-item FFQ. The individual foods were collapsed into sixty-four main food groups and compared using Cox proportional models, adjusting for potential confounders. Hazard ratio (HR) estimates are presented per portion increase in food items. After approximately 18 years of follow-up, there were 1822, 294 and 285 cases of breast, endometrial and ovarian cancer, respectively. A high consumption of processed meat and total meat was associated with an increased risk of breast and endometrial cancer. High intake of tomatoes (HR 0·87, 99 % CI 0·75, 1·00) and dried fruits (HR 0·60, 99 % CI 0·37, 0·97) was associated with a reduced risk of breast and endometrial cancer, respectively. Mushroom intake was associated with a higher risk of ovarian cancer (HR 1·57, 99 % CI 1·09, 2·26). Subgroup analysis by pre- or postmenopausal cancer further demonstrated an association between processed meat intake and both postmenopausal breast cancer and endometrial cancer. Intake of dried fruits was associated with a reduced risk of postmenopausal endometrial cancer (HR 0·55, 99 % CI 0·31, 0·98). Our findings suggest that while some foods may trigger the risk of these cancers, some foods may also be protective; supporting the call for further randomised controlled trials of dietary interventions to reduce the risk of cancer among pre- and postmenopausal women.

scholarly journals Statistical Meta-Analysis of Risk Factors for Endometrial Cancer and Development of a Risk Prediction Model Using an Artificial Neural Network Algorithm

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3689
Author(s):  
Suzanna Hutt ◽  
Denis Mihaies ◽  
Emmanouil Karteris ◽  
Agnieszka Michael ◽  
Annette M. Payne ◽  
...  
Keyword(s):  
Neural Network ◽  
Risk Factors ◽  
Endometrial Cancer ◽  
Computational Model ◽  
Rank Order ◽  
Meta Analysis ◽  
The Neural Network ◽  
Increased Risk ◽  
Neural Network Algorithm ◽  
Risk Of Cancer

Objectives: In this study we wished to determine the rank order of risk factors for endometrial cancer and calculate a pooled risk and percentage risk for each factor using a statistical meta-analysis approach. The next step was to design a neural network computer model to predict the overall increase or decreased risk of cancer for individual patients. This would help to determine whether this prediction could be used as a tool to decide if a patient should be considered for testing and to predict diagnosis, as well as to suggest prevention measures to patients. Design: A meta-analysis of existing data was carried out to calculate relative risk, followed by design and implementation of a risk prediction computational model based on a neural network algorithm. Setting: Meta-analysis data were collated from various settings from around the world. Primary data to test the model were collected from a hospital clinic setting. Participants: Data from 40 patients notes currently suspected of having endometrial cancer and undergoing investigations and treatment were collected to test the software with their cancer diagnosis not revealed to the software developers. Main outcome measures: The forest plots allowed an overall relative risk and percentage risk to be calculated from all the risk data gathered from the studies. A neural network computational model to determine percentage risk for individual patients was developed, implemented, and evaluated. Results: The results show that the greatest percentage increased risk was due to BMI being above 25, with the risk increasing as BMI increases. A BMI of 25 or over gave an increased risk of 2.01%, a BMI of 30 or over gave an increase of 5.24%, and a BMI of 40 or over led to an increase of 6.9%. PCOS was the second highest increased risk at 4.2%. Diabetes, which is incidentally also linked to an increased BMI, gave a significant increased risk along with null parity and noncontinuous HRT of 1.54%, 1.2%, and 0.56% respectively. Decreased risk due to contraception was greatest with IUD (intrauterine device) and IUPD (intrauterine progesterone device) at −1.34% compared to −0.9% with oral. Continuous HRT at −0.75% and parity at −0.9% also decreased the risk. Using open-source patient data to test our computational model to determine risk, our results showed that the model is 98.6% accurate with an algorithm sensitivity 75% on average. Conclusions: In this study, we successfully determined the rank order of risk factors for endometrial cancer and calculated a pooled risk and risk percentage for each factor using a statistical meta-analysis approach. Then, using a computer neural network model system, we were able to model the overall increase or decreased risk of cancer and predict the cancer diagnosis for particular patients to an accuracy of over 98%. The neural network model developed in this study was shown to be a potentially useful tool in determining the percentage risk and predicting the possibility of a given patient developing endometrial cancer. As such, it could be a useful tool for clinicians to use in conjunction with other biomarkers in determining which patients warrant further preventative interventions to avert progressing to endometrial cancer. This result would allow for a reduction in the number of unnecessary invasive tests on patients. The model may also be used to suggest interventions to decrease the risk for a particular patient. The sensitivity of the model limits it at this stage due to the small percentage of positive cases in the datasets; however, since this model utilizes a neural network machine learning algorithm, it can be further improved by providing the system with more and larger datasets to allow further refinement of the neural network.

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