scholarly journals Estrogen Receptors in Colorectal Cancer: Facts, Novelties and Perspectives

2021 ◽  
Vol 28 (6) ◽  
pp. 4256-4263
Author(s):  
Ilaria Ditonno ◽  
Giuseppe Losurdo ◽  
Maria Rendina ◽  
Maria Pricci ◽  
Bruna Girardi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Estrogen Receptors ◽  
Caspase 3 ◽  
Large Population ◽  
Protective Role ◽  
Opposite Trend ◽  
Menopausal Women ◽  
Apoptotic Pathways ◽  
Advanced Adenomas ◽  
Nuclear Estrogen Receptors

Colorectal cancer (CRC) is the second cause of cancer-related death in both sexes worldwide. As pre-menopausal women are less likely to develop CRC compared to age-matched men, a protective role for estrogens has been hypothesized. Indeed, two isoforms of nuclear estrogen receptors (ER) have been described: ERα and ERβ. While the binding of 17beta-estradiol to ERα activates anti-apoptotic pathways, the interaction with ERβ activates caspase-3, inducing apoptosis. In this regard, several pieces of evidence show that ERβ tends to be under-regulated in advanced adenomas and CRC, with an opposite trend for ERα. Furthermore, ERβ stimulation slows adenomatous polyp growth and modulates relevant CRC pathways. Based on such considerations, dietary modulation of ER is promising, particularly in subjects with genetic predisposition for CRC. Nevertheless, the main limitation is the lack of clinical trials on a large population scale.

Retrospective Review of Multitarget Stool DNA as a Screening Test for Colorectal Cancer

2021 ◽  
pp. 000313482110318
Author(s):  
Thomas K. Kleinschmidt ◽  
Austin Clements ◽  
Mark A. Parker ◽  
Steven D. Scarcliff
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Retrospective Review ◽  
Screening Test ◽  
Hyperplastic Polyps ◽  
Dna Testing ◽  
History Of ◽  
Stool Dna ◽  
Stool Dna Testing ◽  
Advanced Adenomas

Objectives To review the effectiveness of noninvasive multitarget stool DNA testing as a screening test for colorectal cancer. Methods We performed a retrospective review of patients referred to 2 high volume outpatient procedural centers for colonoscopy for positive Cologuard test. Positive findings for colorectal cancer based on pathologic findings and also advanced adenomas were recorded. Positive predictive value (PPV) was assessed. Results Of the 1585 patients evaluated and referred for colonoscopy from January 1, 2018 to November 1, 2019, for ICD-10 codes R19.5 (other fecal abnormalities) and K92.1 (melena), 84 were referred for a positive Cologuard test. Out of the 84, 6 were excluded based on family history of colon cancer in first degree relative or personal history of inflammatory bowel disease. Of the remaining 78 patients, 1 patient (1.3%) had colorectal cancer and 5 (6.4%) had advanced adenomas (>1 cm size, high grade dysplasia or villous). Postive predictive value for colorectal cancer was 1.3% and for precancerous lesions plus colorectal cancer was 7.7%. A total of 53 (68.0%) patients had either totally normal colonoscopy or hyperplastic polyps. Out of the 78 individuals in our study, 70 (89.7%) had normal findings, hyperplastic polyps, or non-advanced adenomas. Conclusions Multitarget stool DNA testing carries an unacceptably low PPV to be utilized as a screening test for colorectal cancer. The study fails to detect both adenomas and colon cancer at a higher rate than screening colonoscopy in selected studies. The advantage of being noninvasive has been noted to increase colorectal cancer screening in otherwise non-compliant Medicare patients.

scholarly journals Differential role of SIRT1/MAPK pathway during cerebral ischemia in rats and humans

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sireesh Kumar Teertam ◽  
Phanithi Prakash Babu
Keyword(s):  
Cerebral Ischemia ◽  
Caspase 3 ◽  
Mapk Pathway ◽  
Protective Role ◽  
Akt Signaling ◽  
Sirtuin 1 ◽  
Neurological Dysfunction ◽  
Dependent Manner ◽  
Erk Mapk

AbstractCerebral ischemia (CI) is a severe cause of neurological dysfunction and mortality. Sirtuin-1 (Silent information regulator family protein 1, SIRT1), an oxidized nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, plays an important role in protection against several neurodegenerative disorders. The present study aims to investigate the protective role of SIRT1 after CI in experimental young and aged rats and humans. Also, the study examines the possible regulatory mechanisms of neuronal death in CI settings. Immunoblotting and immunohistochemistry were used to evaluate changes in the expression of SIRT1, JNK/ERK/MAPK/AKT signaling, and pro-apoptotic caspase-3 in experimental rats and CI patients. The study findings demonstrated that, in aged experimental rats, SIRT1 activation positively influenced JNK and ERK phosphorylation and modulated neuronal survival in AKT-dependent manner. Further, the protection conferred by SIRT1 was effectively reversed by JNK inhibition and increased pro-apoptotic caspase-3 expression. In young experimental rats, SIRT1 activation decreased the phosphorylation of stress-induced JNK, ERK, caspase-3, and increased the phosphorylation of AKT after CI. Inhibition of SIRT1 reversed the protective effect of resveratrol. More importantly, in human patients, SIRT1 expression, phosphorylation of JNK/ERK/MAPK/AKT signaling and caspase-3 were up-regulated. In conclusion, SIRT1 could possibly be involved in the modulation of JNK/ERK/MAPK/AKT signaling pathway in experimental rats and humans after CI.

scholarly journals Immunochemical Fecal Occult Blood Test for Detection of Advanced Colonic Adenomas and Colorectal Cancer: Comparison with Colonoscopy Results

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Bianca Rosa Viana Freitas ◽  
Cristiane Kibune Nagasako ◽  
Celia Regina Pavan ◽  
Sônia Letícia Silva Lorena ◽  
Fabio Guerrazzi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Sensitivity And Specificity ◽  
Occult Blood ◽  
Fecal Occult Blood ◽  
Screening Programs ◽  
Fecal Occult ◽  
Colonic Adenomas ◽  
Lack Of Information ◽  
Risk Patients ◽  
Advanced Adenomas

Background. Fecal immunochemical tests (FITs) have been used for colorectal cancer (CRC) screening in several countries. There is lack of information concerning diagnostic performances of this method in Brazil.Methods. Patients scheduled for elective colonoscopy provided one stool sample one week before colonoscopy. The accuracy of a qualitative FIT for detection of CRC and advanced adenomas was determined.Results. Overall 302 patients completed the study. Among them, 53.5% were high risk patients referred for screening or surveillance. Nine (3%) CRCs and 11 (3.6%) advanced adenomas were detected by colonoscopy. Sensitivity and specificity for CRC were, respectively, 88.9% and 87.6%. For advanced adenomas, sensitivity was 63.6% and specificity 87.6%.Conclusion. Our results showed good sensitivity and specificity of the FIT for detecting advanced neoplasias. This method may be a valuable tool for future screening programs in Brazil.

Abstract 097: Recombinant Human Erythropoietin Prevents Reactive Oxygen Species - Induced Apoptosis Via Akt and p38 MAPK Pathway During Hypoxia/ Reperfusion Injury

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Asiya Parvin Allaudeen ◽  
Ajay Devendran ◽  
John E Baker ◽  
Anuradha Dhanasekaran
Keyword(s):  
Reactive Oxygen Species ◽  
P38 Mapk ◽  
Caspase 3 ◽  
Mapk Pathway ◽  
Intact Cell ◽  
Reactive Oxygen ◽  
Protective Role ◽  
Oxygen Species ◽  
Human Erythropoietin ◽  
In Cells

Erythropoietin (EPO) is a cytokine produced primarily in the kidney that is essential for red blood cell production. Apart from playing a role in hematopoiesis, EPO also has a protective role in heart myocytes, ovarian, glial cells brain and retinal diseases. In this study we observed that recombinant human EPO (rhEPO) reduces Hypoxia/ Reperfusion (H/R) injury by virtue of its effect on EPO receptor prosurvival signaling pathway, which ultimately leads to reduced expression of apoptotic proteins and increased survival of cardiomyocytes. H9C2 cells were exposed to H/R with or without pretreatment using 10, 15 and 20 U/ml of rhEPO. We determined viability using MTT, nuclear fragmentation by Hoechst staining, apoptotic nuclei by Acridine orange and Ethidium bromide, Reactive Oxygen Species (ROS) by Dicholorofluoresin Diacetate and activity of late apoptotic protease, Caspase-3 by colorimetric Caspase-3 assay. The expression of mitochondrial superoxide dismutase (MnSOD) by RT-PCR and Western blot, phospho-Akt and p38 MAPK by Confocal microscopy were analyzed. Cell viability is increased in cells pretreated with rhEPO compared to cell exposed to H/R. Cells subjected to H/R showed early apoptotic and late apoptotic cells but showed normal nuclei with intact cell membrane in cells pretreated with rhEPO. Intracellular production of ROS and Caspase-3 activity was decreased in cells pretreated with rhEPO compared to cells exposed to H/R. The expression of MnSOD RNA and protein was up-regulated in response to rhEPO, but not in H/R. The phosphorylative activation of Akt, p38MAPK progressively diminished during H/R but increased in rhEPO pretreated cells. We show that rhEPO prevents apoptosis in cardiomyocytes, subjected to H/R injury via phosphorylation of Akt and p38MAPK. These results it is hoped would help us distinguish the cell signaling pathways involved in cardioprotection and thus would open new avenues in cardiovascular therapy.

scholarly journals Protective role of ABCG2 against oxidative stress in colorectal cancer and its potential underlying mechanism

2018 ◽  
Author(s):  
Shuang Nie ◽  
Yaqing Huang ◽  
Mengyue Shi ◽  
Xuetian Qian ◽  
Hongzhen Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Underlying Mechanism ◽  
Protective Role

scholarly journals THE PROTECTIVE ROLE OF SOCIAL SUPPORT ON DEPRESSIVE SYMPTOMS AMONG AGING SEXUAL MINORITY CANADIANS

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S303-S304
Author(s):  
Arne Stinchcombe ◽  
Nicole G Hammond ◽  
Kimberley Wilson
Keyword(s):  
Social Support ◽  
Older Adults ◽  
Depressive Symptoms ◽  
Sexual Orientation ◽  
Sexual Minority ◽  
Large Population ◽  
Population Based ◽  
Protective Role ◽  
Linear Regression Models ◽  
And Bisexual

Abstract Sexual minority older adults face minority stressors that are associated with higher rates of mental illness. The stress buffering effects of social support within majority populations are well documented. Using a large population-based sample of aging Canadians, we sought to examine the relationship between sexual orientation and depressive symptoms, and determine whether this relationship is moderated by social support and sex. Baseline data from the Canadian Longitudinal Study on Aging (CLSA) were used (n = 46147). Participants were between the ages of 45-85 years at time of recruitment (mean age = 62.46, SD = 10.27), and self-reported their sexual orientation as heterosexual or lesbian, gay, or bisexual (LGB) (2.1%). Social support and depressive symptoms were measured using validated instruments. Four functional social support subscales were derived: tangible, positive social interaction, affectionate, and emotional/informational. Multiple linear regression models adjusted for relevant covariates were conducted. LGB identification was associated with greater depressive symptoms when compared to heterosexual participants (p = 0.032). As evidenced by a significant 3-way interaction (p = 0.030), increasing tangible social support was associated with a corresponding decrease in the risk of depressive symptoms; this relationship was most pronounced for lesbian and bisexual women. A significant 2-way interaction (p = 0.040) revealed that as emotional/informational social support increased, depressive symptoms decreased, with greater disparity between LGB and heterosexual participants at lower levels of social support. The results highlight the importance of social support in promoting mental health, especially among sexual minority older adults.

scholarly journals Overexpression of IRS-4 Correlates with Procaspase 3 Levels in Tumoural Tissue of Patients with Colorectal Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-14
Author(s):  
Patricia Sanmartín-Salinas ◽  
Luis G. Guijarro
Keyword(s):  
Colorectal Cancer ◽  
Caspase 3 ◽  
Cultured Cells ◽  
Cyclin Dependent Kinase ◽  
Kinase Activation ◽  
Tnm System ◽  
Protein Levels ◽  
Receptor Signalling ◽  
T Values

We reported that insulin receptor substrate 4 (IRS-4) levels increased in tissue from colorectal cancer (CRC) patients and promoted retinoblastoma-cyclin-dependent kinase activation. The aim of the present study was to evaluate the effect of IRS-4 on IGF-1 receptor pathway and its impact on procaspase 3 and PARP expression in RKO and HepG2 cancer cell lines. The results obtained in vitro were compared with those obtained from biopsies of patients with CRC (n = 18), tubulovillous adenomas (TA) (n = 2) and in matched adjacent normal colorectal (MANC) tissue (n = 20). IRS-4 overexpression in cultured cells induced the overactivation of IGF-1/BRK/AKT/GSK-3/β-catenin/cyclin D1 pathways, which led to increased expression of procaspase 3 and PARP protein levels. Studies carried out on CRC and TA tissues revealed the overactivation of the IGF-1 receptor signalling pathway, as well as the overexpression of procaspase 3 and PARP in tumoural tissue with respect to MANC tissue. The upregulation of IRS-4 in tumoural samples correlated significantly with the increase in pIGF-1 receptor (Tyr 1165/1166) (r = 0.84; p < 0.0001), procaspase 3 (r = 0. 77; p < 0. 0005) and PARP (r = 0. 89; p < 0. 0005). Similarly, we observed an increase in the proteolysis of procaspase 3 in tumoural tissue with respect to MANC tissue, which correlated significantly with the degradation of PARP (r = 0.86; p < 0.0001), p53 (r = 0.84; p < 0.0001), and GSK-3 (r = 0.78; p < 0.0001). The stratification of patient samples using the TNM system revealed that procaspase 3 and caspase 3 increased gradually with T values, which suggests their involvement in the size and local invasion of primary tumours. Taken together, our findings suggest that IRS-4 overexpression promotes the activation of the IGF-1 receptor pathway, which leads to the increase in procaspase 3 levels in CRC.

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