Soluble Fas Levels Research Articles

A connection between levels of soluble Fas and Fas ligand in the aqueous humor and the parameters of structural and functional damage of glaucoma patients

Introduction/Objective. Fas ligant (FasL) induces apoptosis when interacting with the Fas-receptor. The aim was to determine the concentration of soluble Fas (sFas) and FasL (sFasL) in the aqueous humor of open-angle glaucoma patients, and establish a connection between these markers of apoptosis and the parameters of structural and functional glaucoma damage. Methods. This study examined 88 aqueous humor samples; 35 primary open-angle glaucoma with elevated intraocular pressure (POAG-HTG) patients, 24 open angle pseudoexfoliative glaucoma patients (XFG) and 29 patients with senile cataract (CAT). The concentration of sFas and sFasL was determined by commercial ELISA tests in the aqueous humor. Results. The conducted study showed that aqueous humor sFas concentration was the highest in XFG (720.14 ? 167.39 pg/ml), and slightly lower in POAG-HTG (713.43 ? 162.69 pg/ml), than in cataract patients (632.46 ? 217.11 pg/ml), without statistical significance. There was a significant negative correlation of sFas concentration and RNFL Inf thickness in POAG-HTG (p < 0.05). The concentration of sFasL was the lowest in POAG-HTG (9.28 ? 0.551 pg/ml), higher in XFG (9.45 ? 0.61 pg/ml; p = 0.0566), and the highest in the cataract group (9.48 ? 0.73 pg/ml). A negative correlation of sFasL and MD in the POAG-HTG, and a negative correlation with RNFL Sup in the XFG were significant. Conclusion. sFasL has an active role in the regulation of the inflammatory process in glaucoma. sFas and sFasL, as markers of apoptosis, are associated with the parameters of structural, RNFL thinning, and functional glaucoma damage, namely visual field defects.

CORRELATION BETWEEN LEVEL OF SOLUBLE FAS AND DEGREE OF SEPSIS SEVERITY BASED ON APACHE II SCORE

A widely used scoring system to assess the severity of sepsis is Acute Physiology, Age, and Chronic Health Evaluation (APACHE) II scoring system, however there are some disadvantages in using this. Other parameters are needed to predict severity and outcome of sepsis. Proinflammatory cytokines and Fas receptors are increased in sepsis and their concentration elevations are correlated with disease severity. An increase of soluble Fas level will follow increasing Fas receptors. This study aimed to prove any correlation between the level of soluble Fas and degree of sepsis severity based on APACHE II score. A cross-sectional observational study was conducted in January-June 2015 on 30 septic patients. APACHE II scores were calculated from the patients'physiological data, age, and chronic health problem status. Levels of soluble Fas were measured using the ELISA method (Human FAS/ CD95 (Factor-Related Apoptosis) ELISA Kit, Elabscience Biotechnology). Levels of soluble Fas ranged between 1,049-2,783 pg/mL (1,855.7 ± 477.27 pg/mL). APACHE II scores varied between 4-29 (17.2 ± 5.82). Significant positive correlations between levels of soluble Fas and APACHE II score (r=0.347, p=0.03) were found. A prediction model of soluble Fas levels based on APACHE II score was made. Linear regression analysis produced a prediction model of soluble Fas levels based on APACHE II score, in which soluble Fas level= 1,365.8 + 28.485 x APACHE II score.

Soluble fas levels as a marker in chronic hepatitis C

Objective The aim of the study was to investigate the effect of soluble Fas (sFas) on patients with chronic hepatitis C. Background Programmed cell death has been observed in leukocytes among patients with chronic Hepatitis C and hepatocellular carcinoma (HCC), and now there is a strong trend to use sFas as a predictive marker for chronic hepatitis C and tumorigenesis in HCC. Methods Seventy patients were divided into three groups. Group I included 30 patients with chronic hepatitis C infection due to hepatitis C virus (HCV) (cirrhotic and noncirrhotic). Group II included 20 patients with HCC with HCV infection. Group III included 20 healthy individuals without hepatitis C infection or any other disease, which served as the control group. Liver function tests, complete blood count, analysis of viral markers, analysis of HCV-RNA by PCR, and evaluation of serum sFas by enzyme-linked immunosorbent assay were carried out. Results Serum sFas level increases in chronic hepatitis C and HCC, with positive correlation between sFas and aspartate aminotransferase, alanine aminotransferase, total bilirubin, and direct bilirubin and negative correlation between sFas and Hb level, platelet count, serum albumin, prothrombin time, and viral load (PCR). sFas at cutoff of 6581.12 could predict patients with HCV with 83.3% sensitivity and 65% specificity. sFas at cutoff of 6960.91 could predict patients with HCC with 85% sensitivity and 30% specificity. sFas at cutoff of 9125.99 could discriminate between cirrhotic and noncirrhotic HCV patients with 80.0% sensitivity and 53.3% specificity. Conclusion sFas can be considered a predictive marker for chronic hepatitis C and tumorigenesis in HCC.

96: Serum Levels of Soluble FAS and Soluble FAS Ligand in Pregnant Women Who Smoke

96: Serum Levels of Soluble FAS and Soluble FAS Ligand in Pregnant Women Who Smoke

FAS -670A>G promoter polymorphism is associated with soluble Fas levels in primary Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease characterized by lymphocytic infiltration of exocrine glands. Soluble Fas receptor (sFas) has been suggested as a Fas-mediated apoptosis blocker that could impair clonal deletion in infiltrated autoreactive cells. The FAS -670A>G promoter polymorphism has been studied in pSS. However, a relationship between FAS -670A>G promoter polymorphism and sFas levels in pSS had not been found. We examined this relationship in 77 Mexican pSS patients and 84 healthy subjects were included. Genotypes were identified by PCR-RFLP, and Fas soluble levels were quantified by ELISA. No significant differences between allele and genotype frequencies were found between these two groups. The sFas levels in the serum of pSS patients were significantly higher than in controls (9961 vs 8840 pg/mL, respectively). In addition, AA genotype carriers had significantly higher levels of sFas than GG carriers (pSS: 10,763 and 9422 pg/mL; controls: 9712 and 8305 pg/mL, respectively). An additive model analysis between genotypes (AG+GG vs AA) in both groups, demonstrated a significant association between carriers of the A allele and high sFas levels. In conclusion, carrying the double dose of A allele of FAS -670A>G polymorphism is associated with high levels of sFas in pSS, but it is not a susceptibility marker for pSS.

O nível sérico de Fas solúvel é preditor da necessidade de transfusão de hemácias em pacientes gravemente enfermos

ABSTRACTObjective:To investigate the relation between the need for red blood cell transfusion and serum levels of soluble-Fas, erythropoietin and inflammatory cytokines in critically ill patients with and without acute kidney injury.Methods:We studied critically ill patients with acute kidney injury (n=30) and without acute kidney injury (n=13), end-stage renal disease patients on hemodialysis (n=25) and healthy subjects (n=21). Serum levels of soluble-Fas, erythropoietin, interleukin 6, interleukin 10, iron status, hemoglobin and hematocrit concentration were analyzed in all groups. The association between these variables in critically ill patients was investigated.Results:Critically ill patients (acute kidney injury and non-acute kidney injury patients) had higher serum levels of erythropoietin than the other groups. Hemoglobin concentration was lower in the acute kidney injury patients than in other groups. Serum soluble-Fas levels were higher in acute kidney injury and end-stage renal disease patients. Critically ill patients requiring red blood cell transfusions had higher serum levels of soluble-Fas (5,906±2,047 and 1,920±1,060; p<0.001), interleukin 6 (518±537 and 255+502; p=0.02) and interleukin 10 (35.8±30.7 and 18.5±10.9; p=0.02), better iron status and higher mortality rates in the first 28 days in intensive care unit. Serum soluble-Fas levels were independently associated with the number of red blood cell units transfused (p=0.02). Serum soluble-Fas behaved as an independent predictor of the need for red blood cell transfusion in critically ill patients (p=0.01).Conclusions:Serum soluble-Fas level is an independent predictor of the need for red blood cell transfusion in critically ill patients with or without acute kidney injury. Further studies are warranted to reconfirm this finding.

Soluble Fas and Fas-ligand levels in mid-trimester amniotic fluid and their associations with severe small for gestational age fetuses: a prospective observational study

We aimed to determine the second-trimester amniotic fluid (AF) levels of soluble Fas (sFas) and Fas-ligand (FasL) and investigate their association with fetal growth. Therefore, sFas and FasL levels were measured by enzyme immunoassay in the AF of 21 small for gestational age (SGA), 13 large for gestational age (LGA), and 44 appropriate for gestational age (AGA) fetuses of pregnant women who underwent amniocentesis at between 15 and 22 weeks gestation. Our study results showed that sFas and FasL levels were detectable in AF. sFAS median (25th–75th centile) levels were 3.8 (2.8–4.6)ng/ml in SGA, 3.6 (3.1–4.5)ng/ml in AGA, and 4.0 (3.1–4.4)ng/ml in LGA. FasL median (25th–75th centile) levels were 26.0 (20.3–32.7)pg/ml in SGA, 22.7 (18.4–28.5)pg/ml in AGA, and 21.5 (15.8–30.9)pg/ml in LGA. The differences were not statistically significant. Nevertheless, statistically significant differentiation of FasL levels existed when SGA fetuses in the extremes of distribution (≤5th, ≤2.5th centile) were considered. This is the first study presenting sFas and FasL concentrations in early second-trimester amniotic fluid in AGA, SGA, and LGA fetuses. We found indications that severe and very severe SGA fetuses (≤5th and ≤2.5th centile) have high levels of FasL in the amniotic fluid. This finding probably reflects the increased rate of apoptosis that is assumed to exist in cases of extreme growth restriction.

Proinflammatory Cytokine Activation Is Linked to Apoptotic Mediator, Soluble Fas Level in Patients With Chronic Heart Failure

The Fas/Fas Ligand system is a major apoptosis signaling pathway that is up-regulated in patients with chronic heart failure (CHF). Serum soluble Fas (sFas) levels increase in proportion to the CHF severity and may have prognostic value, therefore, sFas is a promising biomarker of heart failure. In this study, we attempted to identify the determinants of sFas levels in patients with CHF. Serum levels of tumor necrosis factor (TNF)-α and its soluble receptors (sTNF-R1 & sTNF-R2), interleukin (IL)-6, soluble IL-6 receptor (sIL-6R), glycoprotein (gp)130, and sFas were measured in 106 patients with CHF and 39 controls. All subjects performed a symptom-limited cycle ergometer exercise test with expired gas analysis. CHF patients had higher levels of TNF-α, sTNF-R1, sTNF-R2, IL-6, and gp130. Serum levels of sFas (controls versus CHF; 2.60 ± 0.88 versus 3.38 ± 1.23 ng/mL, P = 0.0004) were higher in CHF. On univariate analysis, age (P = 0.0003), NYHA functional class (P = 0.0012), peak VO<inf>2</inf> (P < 0.0001), plasma norepinephrine (P = 0.0013), log IL-6 (P < 0.0001), log TNF-α (P = 0.0002), log sTNF-R1 (P < 0.0001), and log TNF-R2 (P < 0.0001) were significantly related to log sFas levels. Multivariate analysis showed that age and log IL-6 and log sTNF-R1 levels were independently associated with log sFas levels (overall R = 0.603, P < 0.0001). Serum levels of sFas were increased in patients with CHF, and age and serum IL-6 and sTNF-R1 levels were independent determinants of sFas levels. These data suggest that proinflammatory cytokine activation is linked to the Fas/Fas Ligand system in patients with CHF.

The Involvement of Epithelial Fas in a Human Model of Graft Versus Host Disease

Graft-versus-host disease (GVHD) is an important complication occurring after hematopoietic stem-cell transplantation (HSCT). Animal model studies have shown the involvement of the Fas (APO-1/CD95)/Fas-Ligand pathway in GVHD pathogenesis, but its association with cutaneous GVHD in human remains to be established. In the present study, Fas involvement in skin damage was assessed using a human skin explant model of GVHD. Fas and FasL expression were measured by immunohistochemistry and blockade of Fas pathway was investigated using an antagonistic anti-human Fas monoclonal antibody. In addition, levels of soluble Fas (sFas) were determined in the serum of patients receiving allogeneic HSCT with and without GVHD. The results showed that Fas up-regulation in the epithelium of human skin explants correlated with graft-versus-host reaction (GVHR) in the skin explant model (P<0.001). Decreased GVHR grades were observed by using a Fas blocking monoclonal antibody. Levels of sFas were increased post-HSCT (P<0.001) but rather than being associated with the severity of GVHD, sFas levels differed with the conditioning treatments the patients received before the HSCT. Higher GVHR grades were associated with increased Fas expression in the epithelium of the skin explants. In addition, by blocking Fas-mediated apoptosis, the GVHR grades were decreased. Our study thus shows the involvement of Fas in cutaneous GVHD damage, and supports the potential use of Fas as a therapeutic target.

Elevated Serum-Soluble Fas in Preeclampsia: Correlation with Clinical, Laboratory, and Doppler Parameters

Objectives. (i) To compare the levels of soluble Fas (sFas) in the sera of patients with variable degrees of preeclampsia and in healthy gravidas; and (ii) to correlate sFas with clinical, laboratory, and Doppler parameters in preeclampsia. Methods. Fifty patients with mild preeclampsia, 50 patients with severe preeclampsia, and 50 healthy normotensive pregnant women (control group) were selected from those admitted to the delivery unit. All were nearly of the same maternal and gestational ages. Patients and controls were subjected to (i) history taking; (ii) general, abdominal, and pelvic examination; (iii) laboratory investigations including serum sFas, total bilirubin, aspartate transaminase, alanine transaminase, creatinine, uric acid, hematocrit value, platelet count, and 24 urinary proteins; (iv) obstetric ultrasound and biophysical profile; (v) Doppler cerebroplacental ratio; and (vi) neonatal assessment after delivery. Results. Serum sFas was significantly higher (p < 0.001) in patients with mild and severe preeclampsia than in normal controls, and in patients with severe preeclampsia than in those with mild disease. In preeclampsia group, sFas correlated positively with systolic (r = 0.386; p < 0.001) and diastolic (r = 0.347; p = 0.001) blood pressures, serum uric acid (r = 0.452; p < 0.001), and urinary protein (r = 0.416; p < 0.001); and correlated negatively with biophysical profile (r = −0.371; p < 0.001), cerebroplacental ratio (r = −0.527; p < 0.001), and birth weight (r = −0.458; p < 0.001). Conclusion. Serum sFas is significantly elevated in preeclampsia and is correlated with some important clinical, laboratory, and Doppler parameters. Further longitudinal studies are recommended to investigate the possible value of sFas as an early predictor of preeclampsia and its severity.

Evidence of a Significant Role for Fas-Mediated Apoptosis in HCV Clearance during Pegylated Interferon plus Ribavirin Combination Therapy

The role of apoptosis in treatment-induced HCV clearance is controversial. We sought to assess the kinetics of serum apoptosis-related cytokines during pegylated interferon-α2a or -α2b plus weight-based ribavirin therapy for genotype 1 chronic HCV infection. Serum levels of soluble Fas (sFas), soluble Fas ligand (sFasL) and soluble tumour necrosis factor receptor I (sTNF-RI) were measured at baseline, week 12 and 24 weeks after the end of therapy. Sustained virological response (SVR) was achieved in 46% of the 164 included patients, 29% had a non-response (NR) and 25% had relapse (RR). NR patients presented with higher levels of sFasL at baseline and lower levels of sTNF-RI at week 12 as compared to RR and SVR patients. Lower concentrations of sFas were observed in SVR patients 24 weeks after treatment as compared to RR and NR patients. An increase in sFas at week 12 followed by a significant drop 24 weeks after therapy was observed among SVR patients. An increase in sFasL during and after treatment was observed in RR and SVR patients. NR patients exhibited an earlier drop in sTNF-RI levels as compared to RR and SVR patients. Virological response during HCV therapy was associated with an increase of sFas and sFasL, and maintenance of increased concentrations of sTNF-RI.

Circulating progenitor cells in patients with atrial fibrillation and their relation with serum markers of inflammation and angiogenesis

The pathophysiological inter-relationships and underlying 'drivers' of a prothrombotic state in atrial fibrillation (AF) are complex but may include endothelial abnormalities. Circulating progenitor cells (CPCs) have been recently described as a cell population that may promote repair of endothelial damage. We hypothesised abnormalities in this cell population, alongside abnormal markers of endothelial damage/dysfunction (von Willebrand factor, soluble E-selectin), apoptosis (soluble Fas, soluble Fas ligand), angiogenesis (vascular endothelial growth factor) and inflammation (interleukin-6) in 135 consecutive AF patients (14 with lone AF), who were compared to 33 'disease controls' and 13 healthy controls. We also explored whether restoration of sinus rhythm would alter these indices. No significant differences in research indices were observed between AF and disease controls, apart from soluble Fas levels (p<0.001). Median CPC levels in lone AF were higher compared to 'non-lone AF' (that is, AF patients with co-morbidities) [p<0.001], apparently because of difference in age and presence of co-morbidities. There was an increase in CPC counts (p=0.007), but in not other markers following DC cardioversion. CPCs increased significantly in the 17 patients who were successfully cardioverted into sinus rhythm (p=0.003). In a stepwise multiple regression analysis, age (p=0.014), hyperlipidaemia (p=0.001) and use of statins (but not AF) was predictive of CPC counts (p=0.014). In conclusion, AF is unlikely to be independently associated with abnormalities in CPCs. Successful cardioversion is associated with a modest but significant increase in CPCs.

Serum-soluble Fas and serum levels of erythropoietin in chronic kidney disease

Soluble Fas levels (sFas) are increased in the serum of uremic patients and are associated with the presence of anemia and recombinant human EPO (rHuEPO) dosage in dialysis patients. It is possible that sFas levels are associated with an increased need for serum erythropoietin levels (Epo) in chronic kidney disease and dialysis patients in order to maintain hematocrit (Hct) levels. To investigate the relationship between serum sFas levels, serum Epo levels and the ratio between Epo levels and Hct in uremic patients. We studied 52 predialysis chronic kidney disease patients (CKD; 33 M, 57 +/- 12 years, hematocrit (Hct) = 37 +/- 7%), 29 peritoneal dialysis patients (PD; 12 M, 54 +/- 14 years, Hct = 36 +/- 7%), 29 hemodialysis patients (HD; 19 M, 47 +/- 14 years, Hct = 33 +/- 5%) and 29 healthy volunteers (control group 17 M, 50 +/- 16 years, Hct = 43 +/- 3%). We examined the relationship between Hct and serum levels of Epo, sFas, C-reactive protein, IL-6 and iron status. The ratio of serum Epo divided by Hct (Epo/Hct) was used as an indicator of Epo responsiveness. Compared to normal subjects, the CKD, PD and HD groups presented lower Hct levels and higher serum levels of sFas, Epo, Epo/Hct and IL-6. Serum levels of sFas correlated negatively with albumin (r = -0.24, p = 0.02), IL-6 (r = -0.18, p = 0.04) and Epo/Hct (r = -0.37, p < 0.001). In multivariate analysis, after adjusting for markers of iron store and inflammation, only sFas correlated with Epo/Hct. In the CKD group, there were negative correlations between serum levels of sFas and glomerular filtration rate (GFR) (r = -0.45, p < 0.001) and between Epo/Hct and GFR (r = -0.32; p = 0.02). There was a positive correlation between Epo/Hct and serum levels of sFas in the CKD group (r = 0.31, p = 0.03) and in the HD groups (r = 0.58, p = 0.001). Our findings show that serum sFas is associated with higher Epo/Hct ratio, suggesting that sFas may be a marker of Epo hyporesponsiveness in uremia. Further studies are needed to determine whether sFas is just a marker of Epo hyporesponsiveness or is also involved in its pathophysiology.

422: Amniotic fluid soluble FAS level in intruterine growth restriction

422: Amniotic fluid soluble FAS level in intruterine growth restriction

Effect of Quinapril on In-Stent Restenosis and Relation to Plasma Apoptosis Signaling Molecules

Angiotensin-converting enzyme inhibitors have been reported to inhibit in-stent restenosis. To assess the effect of angiotensin-converting enzyme inhibition on in-stent restenosis and its relation to apoptosis, 86 patients with chronic coronary artery disease who required stent implantation in the left anterior descending coronary artery or a major diagonal branch were studied. Patients were randomized to receive quinapril 40 mg/day orally (n = 43) or a placebo (n = 43). Drug therapy was initiated 1 week before initial stenting and continued for 6 months. Plasma levels of the apoptotic signaling molecules soluble Fas and soluble Fas ligand obtained from blood drawn from the left anterior descending coronary artery were measured just before initial stenting and 6 months later, at the time of repeat coronary angiography. In-stent restenosis was present in 9.3% of patients in the quinapril group and 25.6% of patients in the placebo group (p = 0.047). Mean late luminal loss was 0.56 +/- 0.51 mm in the quinapril group and 0.95 +/- 0.95 mm in the placebo group (p = 0.003). There were no significant differences in plasma soluble Fas or soluble Fas ligand levels at baseline. At 6 months, the change in plasma soluble Fas level was significantly higher in the quinapril group (0.72 +/- 1.24 ng/ml) than in the placebo group (0.28 +/- 0.72 ng/ml) (p = 0.024). The change in plasma soluble Fas ligand levels at 6 months was significantly higher in the quinapril group (7.43 +/- 12.2 pg/ml) than in the placebo group (0.06 +/- 6.8 pg/ml) (p = 0.002). In conclusion, the angiotensin-converting enzyme inhibitor quinapril inhibits in-stent restenosis by stimulating apoptosis after percutaneous intervention.

Cancer and Soluble FAS

A test system developed by the authors was used to measure serum concentrations of soluble Fas in patients with malignant and benign tumors of different location and morphology. Relationships between soluble Fas levels and the main clinical and morphological characteristics of cancer were evaluated. It is proven that the concentrations and incidence of detection of soluble Fas in the sera of patients with tumors are significantly higher than in normal subjects. No appreciable differences in the concentrations of soluble Fas were detected in malignant and benign tumors of the mammary gland, bones, ovaries, and adrenals. In thyroid cancer, soluble Fas levels were higher than in benign and hyperplastic processes in this organ. High level of soluble Fas is associated with late stages of the disease (ovarian cancer, cancer of the corpus uteri, adrenocortical and colorectal cancer) and with poor differentiation of the tumor (ovarian cancer and cancer of the corpus uteri), with local metastases (colorectal and adrenocortical cancer), and with tumor invasion into the myometrial tissue, intestinal wall, and adjacent tissues (cancer of the corpus uteri and colorectal cancer). A significantly high level of soluble Fas was detected in colorectal and adrenocortical cancer in the presence of at least 2 local metastases. Soluble Fas levels depended on tumor histogenesis in malignant and benign ovarian tumors. High concentration of soluble Fas was detected in large tumors in patients with ovarian cancer, cancer of the corpus uteri, colorectal cancer, thyroid cancer and adenoma, and in adrenocortical cancer. Initially high levels of soluble Fas are characteristic of patients whose tumors are little sensitive to nonadjuvant radiotherapy. The overall 5-year survival of patients with low levels of soluble Fas is better in osteosarcoma, cancer of the corpus uteri, ovarian and adrenocortical cancer.

Serum soluble Fas level determines clinical outcome of patients with diffuse large B-cell lymphoma treated with CHOP and R-CHOP

We previously reported that serum concentrations of soluble Fas (sFas) predict the clinical outcome of patients with diffuse large B cell lymphoma (DLBCL) after treatment with CHOP but without rituximab (R). Here, we investigated whether the role of sFas as a prognostic factor remains valid in the R-CHOP era. We treated 132 patients with DLBCL between October 1995 and September 2002 (group A: without rituximab), and 75 between December 2002 and March 2007 (group B: with rituximab). The patients received eight cycles of CHOP or THP (tetrahydropyranyl-adriamycin)-COP before September 2002, and R-CHOP or R-THP-COP after October 2002. The distribution of patients according to the International Prognostic Index did not significantly differ between the groups. The 5-year overall survival (OS) rates for patients with sFas levels of > or = 3.0 and <3.0 ng/ml in group A were 19.8 and 61.9% (P < 0.0001), whereas the 3-year OS rates in group B were 54.7 and 92.2% (P < 0.01), respectively. Multivariate analysis using the proportional hazards model revealed that sFas most significantly correlated with overall survival (P < 0.05). Serum sFas is thus a useful tool for selecting the appropriate therapeutic strategy for DLBCL.

Serum Levels of Soluble Fas in Patients with Multinodular Goiter

Objective: Fas is a cell-surface receptor responsible for induction of apoptosis in human thyrocytes upon interaction with Fas Ligand. Fas protein expression on thyroid cells and Fas-mediated apoptosis is decreased in multinodular goiter (MNG) resulting in thyroid cell proliferation. The soluble form of Fas (sFas) produced by alternative mRNA splicing may inhibit Fas-Fas Ligand binding and apoptosis. The aim of this study was to examine whether sFas is differentially expressed in multinodular goiter (MNG), which is associated with decreased Fas-mediated apoptosis. Method: We determined serum sFas levels using enzyme-linked immunosorbent assay (ELISA) in 42 patients with MNG and 23 normal controls. Results: Serum sFas levels were increased in patients with MNG (7.47 ± 2.55 ng/ml) compared to normal controls (2.26 ± 0.9 ng/ml). Levels of sFas were not significantly correlated with age, sex or clinical parameters, such as serum levels of FT4 or TSH. Discussion: Increased sFas in MNG may indicate increased expression of alternatively spliced Fas mRNA variant and decreased expression of cell-surface Fas protein, and may enhance thyroid cell proliferation by protecting thyroid cells from Fas-mediated apoptosis.

Soluble Fas level and cancer mortality: Findings from a nested case–control study within a large‐scale prospective study

Soluble Fas (sFas) is known to play an important role in the development of cancers of various sites. To confirm whether or not the serum sFas level can be a predictor of cancer, we conducted a nested case-control study within a large-scale population-based cohort study in Japan. Serum samples were collected from 39,242 participants (13,839 men and 25,403 women) at baseline, all of whom were followed until 1997 for mortality and until 1994 for cancer incidence. Three controls were randomly selected and matched to each cancer case for gender, age and residential area. Serum values of sFas were measured by enzyme-linked immuno-adsorbent assay, using commercially available kits. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using conditional logistic models, based on 798 total cancer mortality cases and their 2,353 matched controls. The risk of total cancer mortality was increased according to sFas levels, and the OR of the highest quartile compared with that of the lowest was 1.81 (95% CI; 1.40-2.34) after adjusting for smoking and drinking status, and body mass index. This positive association remained unaltered when cases were divided into 2 groups according to the observation period. Our results suggest that serum sFas has a possibility to detect people at high risk for cancer prior to diagnosis, since it increased before cancer diagnosis in those apparently healthy people.

Serum Apoptosis Markers in Acute Liver Failure: A Pilot Study

We sought to determine whether circulating apoptotic markers are altered in acute liver failure (ALF), differ with etiology, or predict clinical outcome in this condition. Serum levels of soluble Fas (sFas), tumor necrosis factor-alpha (TNF-alpha), hepatocyte growth factor (HGF), and interleukin-6 (IL-6) were measured in 67 acute liver failure patients, as well as controls. In a subset of the groups, we measured serum M-30 antigen, an exposed neoepitope from caspase cleavage. We also assessed M-30 immunoreactivity in liver tissue of ALF patients and controls. Median levels for TNF-alpha, HGF, IL-6, and M-30 antigen were at least 10-fold greater in ALF than in hepatitis C virus or normal controls (P < .0001). Median day 1 sFas, day 3 sFas, and day 1 HGF levels varied according to etiology of acute liver failure (P = .004, P = .011, and P = .019, respectively), with values for drug-induced liver injury and acetaminophen-related ALF higher than other etiologies. Median M-30 antigen levels were significantly higher in patients who were transplanted and/or died (2183 U/L) than spontaneous survivors (1004 U/L) (P = .026). M-30 immunoreactivity in liver tissue was significantly greater in ALF patients than HCV controls (P = .004). TNF-alpha, HGF, IL-6, and M-30 antigen were significantly elevated in ALF. High levels of sFas and HGF might help to confirm a diagnosis of drug-induced liver injury or acetaminophen-related ALF. Higher levels of M-30 antigen are associated with poor clinical outcomes in ALF.