Higher Carbohydrate Antigen 125 Levels Are Associated with Increased Risk of Coronary Heart Disease in Elderly Chinese: A Population-Based Case-Control Study

Background: High carbohydrate antigen 125 (CA-125) level was reported to be associated with some cardiac dysfunctions, such as chronic heart failure, but the relationship between CA-125 level and coronary heart disease (CHD) risk remains unclear. The aim of this study was to explore the potential association in a Chinese older population. Methods: In a population-based case-control study conducted in a Chinese older population, serum CA-125 levels were measured in 1177 diagnosed CHD patients and 3531 age and sex matched control subjects without CHD. Results: Serum CA-125 level was significantly higher in CHD patients than controls (P < 0.001) with adjustment for age, gender, smoking, drinking, BMI, physical activity, hypertension, dyslipidemia, diabetes mellitus, medication history and family history of CHD and myocardial infarction. CHD risk was doubled (OR: 2.10, 95%CI: 1.69-2.60) among subjects in the highest quartile compared to those in the lowest quartile of CA-125 level (Ptrend < 0.001). Furthermore, CA-125 levels were associated with CHD risks in subjects with age over 60 years (OR: 2.19, 95%CI: 1.75-2.73), current smokers (OR: 2.29, 95%CI: 1.50-3.49), current drinkers (OR: 2.35, 95%CI: 1.57-3.53) and subjects with hypertension (OR: 2.04, 95%CI: 1.71-2.43). Conclusions: Elevated serum CA-125 level might be associated with increased risk of coronary heart disease in the Chinese older population. Further investigations are needed to identify the possible biological role of CA-125 in CHD development in the future

Carbohydrate antigen 125 in congestive heart failure: ready for clinical application?

Congestion is the permanent mechanism driving disease progression in patients with acute heart failure (AHF) and also is an important treatment target. However, distinguishing between the two different phenotypes (intravascular congestion and tissue congestion) for personalized treatment remains challenging. Historically, carbohydrate antigen 125 (CA125) has been a frequently used biomarker for the screening, diagnosis, and prognosis of ovarian cancer. Interestingly, CA125 is highly sensitive to tissue congestion and shows potential for clinical monitoring and optimal treatment of congestive heart failure (HF). Furthermore, in terms of right heart function parameters, CA125 levels are more advantageous than other biomarkers of HF. CA125 is expected to become a new biological alternative marker for congestive HF and thereby is expected be widely used in clinical practice

Biological significance of cancer antigen 125

Morphological changes including fibrosis, vascular degeneration and loss of mesothelium occur to the peritoneal membrane during peritoneal dialysis. The loss of mesothelium is thought to effect peritoneal homeostasis and host defence, as these cells play a pivotal role in these organs response to inflammation. Cancer antigen 125 (CA125), a mucilaginous high molecular weight glycoprotein, has been used as a marker of peritoneal mesothelial cells mass/turnover and membrane functional integrity in peritoneal dialysis patients. The use of new more biocompatible dialysis solutions is associated with an increase in CA125 effluent concentration, however it's precise molecular nature, function and regulation is poorly defined. This study investigates the transcriptional mechanisms regulating CA125 expression in human peritoneal mesothelial cells as well as CA125's regulation in response to inflammation. Additionally, CA125's function in the process of mesothelial cell repair is examined using a novel mesothelial wound healing system. These investigations have: Successfully reconstructed the genomic structure of CA125 and characterised its proximal promoter region. Demonstrated regulation of CA125 cell surface expression and shedding in response to IL-1 p and IL-6 trans-signalling. Shown the retardation of human peritoneal mesothelial cell CA125 shedding in response to high levels of glucose degradation products present within peritoneal dialysis fluids. Shown the improved wound healing of mesothelial cells in response to elevated CA125 levels. These investigations have clarified existing discrepancies regarding CA125 regulation during inflammation by demonstrating its altered expression at the cell surface, in response to inflammatory mediators. Additionally, this work has linked clinical Observations regarding CA125 effluent levels during peritoneal dialysis to a potential role of CA125 in wound healing of the mesothelium.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Biological significance of cancer antigen 125.

Morphological changes including fibrosis, vascular degeneration and loss of mesothelium occur to the peritoneal membrane during peritoneal dialysis. The loss of mesothelium is thought to effect peritoneal homeostasis and host defence, as these cells play a pivotal role in these organs response to inflammation. Cancer antigen 125 (CA125), a mucilaginous high molecular weight glycoprotein, has been used as a marker of peritoneal mesothelial cells mass/turnover and membrane functional integrity in peritoneal dialysis patients. The use of new more biocompatible dialysis solutions is associated with an increase in CA125 effluent concentration, however it's precise molecular nature, function and regulation is poorly defined. This study investigates the transcriptional mechanisms regulating CA125 expression in human peritoneal mesothelial cells as well as CA125's regulation in response to inflammation. Additionally, CA125's function in the process of mesothelial cell repair is examined using a novel mesothelial wound healing system. These investigations have: Successfully reconstructed the genomic structure of CA125 and characterised its proximal promoter region; Demonstrated regulation of CA125 cell surface expression and shedding in response to IL-1 p and IL-6 trans-signalling; Shown the retardation of human peritoneal mesothelial cell CA125 shedding in response to high levels of glucose degradation products present within peritoneal dialysis fluids; Shown the improved wound healing of mesothelial cells in response to elevated CA125 levels. These investigations have clarified existing discrepancies regarding CA125 regulation during inflammation by demonstrating its altered expression at the cell surface, in response to inflammatory mediators. Additionally, this work has linked clinical observations regarding CA125 effluent levels during peritoneal dialysis to a potential role of CA125 in wound healing of the mesothelium

Study of inflammatory signalling in epithelial ovarian cancer and the normal human mesothelium

Epithelial Ovarian Cancer (EOC) kills more women annually in the United Kingdom than any other gynaecological cancer. Survival rates for women diagnosed with EOC have not improved over the past 30 years, due to the often advanced stage at presentation, where widespread intra-peritoneal dissemination has occurred. The natural history of the disease remains uncertain but the ovarian surface epithelium (OSE) is a strong candidate for the tissue of origin. The OSE undergoes cyclical damage and repair in women of reproductive age following ovulation, which can be considered an acute inflammatory event. Factors that prevent ovulation (pregnancy, breastfeeding and contraceptive pill use) also protect against the development of EOC. Previously published data show that the OSE is able to upregulate the enzyme 11-beta hydroxysteroid dehydrogenase type 1 (11βHSD1) in response to inflammation, the enzyme responsible for converting inactive cortisone to anti-inflammatory cortisol. This thesis hypothesises that 11βHSD isozymes are deregulated in ovarian cancer; that the peritoneal surface epithelium (PSE) is indistinguishable from the OSE in its response to inflammation and should be considered a potential source of some “ovarian cancers”; and finally that the expression of the tumour suppressor gene OPCML (OPioid binding Cell adhesion Molecule-Like) is altered by inflammation. These hypotheses were examined at three levels. Firstly, primary cultures of EOC were established, and glucocorticoid metabolism and the response to inflammation was compared to normal OSE. Results from these investigations reveal that the11βHSD1 response to IL-1α stimulation is impaired in EOC compared to normal OSE at the mRNA level but there is no significant difference when 11βHSD1 enzyme activity is measured in these tissues. When basal levels of 11βHSD1, 11βHSD2 and COX2 are compared amongst untreated samples of EOC and OSE, there was a significant correlation between 11βHSD1 and COX2 mRNA expression (P<0.001). 11βHSD2 mRNA expression was significantly higher in the EOC specimens compared to OSE (P<0.05). Secondly the response to inflammation was compared in primary cultures of human peritoneal surface epithelial (PSE) cells and OSE. The data suggest that the mRNA response to inflammation was similar in OSE and PSE, but that the 11βHSD1 enzyme activity was reduced in PSE (P<0.05), which may result in differences in tissue healing. Finally, the effect of inflammation on the expression of the ovarian cancer associated tumour suppressor gene (TSG), OPCML (OPioid binding Cell adhesion Molecule-Like) and the other members of the IgLON family, was examined in OSE. These results suggest that OPCML mRNA expression can be induced by IL-1α, an effect that is inhibited by cortisol

CA125 production by the peritoneum: in-vitro and in-vivo studies

The source of CA125 synthesis is still debated. Endometrial, peritoneal, ovarian and amniotic cells have been demonstrated to produce and secrete CA125. Different studies show that the peritoneum is a source of CA125. The present study aimed at investigating in vivo and in vitro the peritoneal contribution to circulating CA125. Cultures of uterine peritoneum, abdominal peritoneum and myometrium explants were performed and CA125 measured in the culture medium. To modulate the potential production of CA125, the explants were cultured with or without cycloheximide, bacterial lipopolysaccharide (LPS) or ascitic fluid. In a prospective study, we compared a group of patients after abdominal surgery (n = 19; nine men, 10 women) with a group after extra-abdominal surgery (n = 21; 11 men, 10 women), in order to detect a postoperative increase of serum CA125. De-novo synthesis of CA125 could not be demonstrated in the cultures of uterine and abdominal peritoneum and in myometrium, but CA125 concentrations were detectable in the culture medium without being modulated by cycloheximide, LPS or ascitic fluid. After peritoneal surgery, the proportion of patients with increased serum CA125 was significantly higher (P < 0.03) after abdominal surgery as compared with extra-abdominal surgery. This is considered as indirect evidence for in-vivo production of CA125 by the peritoneu