Level Of sFasL Research Articles

Fas-mediated apoptosis and peripheral polyneuropathy in type 2 diabetes mellitus

ObjectiveTo evaluate the role of soluble Fas (sFas) and soluble Fas ligand (sFasL) in the pathogenesis of distal symmetrical polyneuropathy (DSPN) in patients with type 2 diabetes mellitus, and to analyze the relationship between these apoptotic markers with clinical parameters and electrophysiologic profile of DSPN, as well as with different diabetic factors among those patients.Patients and methodsThe study included 60 Egyptians with type 2 diabetes mellitus. All patients were evaluated clinically for DSPN by using Michigan Neuropathy Screening Instrument. Electrophysiological diagnosis of DSPN was based on the criteria suggested by the European Standardized Telematic tool to Evaluate Electrodiagnostic Methods group. Diabetic patients were divided into two groups according to the electrophysiological findings: group A included patients with DSPN (N=42), and group B included patients without DSPN (N=18). The severity of DSPN among group A patients was assessed clinically using Toronto Clinical Neuropathy Score and electrophysiologically by the severity score proposed by Hidasi and colleagues. The study also included 30 healthy volunteers as a control group. Serum levels of sFas and sFasL were assessed in all the studied groups.ResultsSerum level of sFas was significantly elevated in diabetic patients with DSPN compared with diabetics without DSPN and nondiabetic control (P=0.029 and 0.000). Receiver operating characteristic (ROC) curve analysis detected that sFas was statistically significant in discriminating between diabetic patients with DSPN from those patients without DSPN with an accuracy of 66%. The cutoff point that has the highest sensitivity (61%) and specificity (62%) was 33.3 ng/ml. Serum level of sFas showed a positive significant correlation with the electrophysiological severity of DSPN (P=0.020). Serum level of sFasL did not show statistically significant difference between all the studied groups.ConclusionFas-mediated apoptosis has an important role in the development of diabetic DSPN and is correlated with its electrophysiological severity.

Prognostic Value of Soluble Death Receptor Ligands in Patients with Transitional Cell Carcinoma of Bladder

Background: The activation of Fas/Fas ligand (FasL) and DR4-DR5/tumor necrosis factor-related-apoptosis-inducing ligand (TRAIL) pathways in cancer cells triggers apoptosis. The objective of this study was to investigate the prognostic value of soluble FasL (sFasL) and soluble (sTRAIL) in the serum of patients with bladder cancer. Methods: The sFasL and sTRAIL levels in the sera of patients with bladder cancer or healthy donors were determined using the enzyme-linked immunosorbent assay. Micro-culture tetrazolium viability assay and Western blot were used to analyze cell cytotoxicity and death receptors protein expression respectively. Results: Whether no difference in sTRAIL levels was seen between patients and controls, the level of sFasL was higher in patients than that in healthy donors. According to, sFasL level was the highest in the serum of patients with superficial stage or low- and medium-grade cancer. Moreover, sFasL in patients with superficial noninvasive bladder tumors or low- and medium-grade cancers was higher than that in patients with invasive carcinomas and high-grade cancers. Patients with high levels of sFasL survive longer than those with low levels, probably related to the cytotoxic potential of FasL preserved in its soluble form. Conclusion: The data suggest that monitoring the level of sFasL and its cytotoxic activity could be a prognostic marker in the follow-up of patients with bladder cancer.

A Potential of sFasL in Preventing Gland Injury in Sjogren's Syndrome.

Fas and its ligand FasL, members of tumor necrosis factor receptor superfamily, have been implicated in the process of cell apoptosis. FasL consists of two forms, membrane FasL (mFasL) and soluble FasL (sFasL). sFasL can be produced by mFasL cleaved by matrix metalloproteinases (MMP) and also reveals a role for binding to Fas which is expressed on cell surface. Although Fas/FasL axis has been implicated in a variety of diseases, its role in Sjogren's syndrome still remains ill defined. In this study, we investigated the potential of sFasL in the pathogenesis of Sjogren's syndrome (SS). We found that the serum levels of sFasL in SS patients were significantly lower than healthy subjects. Moreover, serum levels of sFasL in patients with mild disease activity were higher than patients with severe disease activity. There is a positive correlation of the serum level of sFasL with uptake index of parotid gland in our expectation. In addition, liver injury involvement in SS patients showed decreased level of sFasL. Furthermore, we here also observed that the protective cytokine IL-10 expression was positively correlated with sFasL expression. Thus, our results here suggest a potential of sFasL in maintaining gland organ homeostasis.

Soluble Fas ligand (sFasL) as a predictor of reduction of general psychopathology in schizophrenia after antipsychotic treatment

IntroductionDysregulation of the apoptotic process is associated with the etiopathogenesis of schizophrenia, which is observed at the brain and peripheral blood levels. A significant negative correlation between the duration of the disease and serum sFasL concentration was demonstrated by other authors. It was shown that an increased rate of apoptosis is more pronounced in neuroleptic-free patients with the first-episode of schizophrenia than in patients with chronic disease.AimSearch for a predictor of good response to antipsychotic treatment based on the analysis of the sFasL plasma level and its relationship with clinical symptoms.MethodsFifty-three patients with chronic schizophrenia and 46 healthy individuals were enrolled in the study. The concentration of sFasL was measured by ELISA. Clinical assessments (PANSS, SANS, SAPS) and blood analyses were conducted three times: during the active phase of disease (at admission), after 4 weeks of pharmacotherapy, and after reaching remission.ResultsIn the schizophrenia group, non-altered levels of sFasL (P = 0.1; U Mann-Whitney test), compared to the control, were detected at admission. The initial level of sFasL correlated negatively (r = −0.33; P = 0.04; Spearman's rank) with blood leukocyte count. Despite clinical improvement, no significant changes in the level of sFasL were observed. However, the sFasL level correlated negatively with the PANSS general psychopathology reduction after 4 weeks of pharmacotherapy (r = −0.7; P = 0.04) and after remission (r = −0.39; P = 0.026).ConclusionsThe results indicate a possible role of sFasL in apoptosis of blood leukocytes and suggest that the reduction of sFasL level can predict level of PANSS general psychopathology after antipsychotic treatment in schizophrenia.Disclosure of interestThe authors have not supplied their declaration of competing interest.

FasL-mediated apoptosis in chronic carrageenan-induced gastroenterocolitis

The levels of sFasL and caspase-3 activity were studied in blood serum of rats with chronic gastroenterocolitis developed after intake of carrageenan during 2 and 4 weeks. It was established that the disease was accompanied by increased activity of caspase-3, more considerable in case of more prolonged carrageenan consumption suggesting activation of apoptosis in chronic intestinal carrageenan-induced inflammation. The elevated level of sFASL was observed, which was higher after 2 weeks of carrageenan intake. It indicated the predominance of FasL-mediated apoptosis of enterocytes in the early stages and the significant role of other mechanisms of apoptosis in the later stages of chronic carrageenan-induced intestinal inflammation.

Sulfur Mustard Aerosol Inhalation Injury in Rat Lungs via Fas‐mediated Apoptosis

We have focused on the Fas (death receptor)‐mediated pathway of apoptosis as a major mechanism of sulfur mustard (SM) inhalation injury. We examined the changes in caspase−8, −9, −3 and −6 activities in bronchoalveolar lavage fluid (BALF) cells and in soluble Fas ligand (sFasL) in BALF at 24 hours following SM exposure (3.0 mg/kg SM, 10 minutes) using a ventilated SM aerosol inhalation rat model. We observed that SM inhalation increased all four caspases in BALF cells as well as the level of sFasL in BALF. Caspase−8, −9, −3, and −6 increased 7‐, 10‐, 2‐ and 4‐fold, respectively, compared to their respective sham controls at 24 hours after SM exposure. Immunohistochemical staining in whole lung tissue showed the presence of activated caspase‐3 in SM inhalation‐exposed rat airway and the lung. These findings suggest that SM inhalation causes apoptosis in the airways and the lungs in this rat model. Observed increases in caspase‐8 and sFasL suggest their involvement in the caspase cascade signaling sequence and the Fas‐mediated pathway as seen in vitro in cultured human AEC. However, these observations need to be validated by studying the relationships between caspase‐3 and the other caspases. In conclusion, these results should be useful in determining the pathogenic mechanisms as well as therapeutic targets for SM inhalation injury. Research was funded by DTRA – Joint Science and Technology Office, Medical S&T Division.

Dysregulation of the Fas/FasL system in mononuclear cells recovered from peritoneal fluid of women with endometriosis

In endometriosis, regurgitating endometrial cells fail to undergo apoptosis and implant themselves outside the uterus, particularly in the peritoneum. We studied Fas and FasL behaviour by evaluating the percentages of mFas and mFasL-bearing mononuclear cells from peritoneal fluid, the level of Fas and FasL gene expression at both mRNA and protein levels in the same cells, and the sFas and sFasL values in peritoneal fluid of 80 endometriotic women, at four stages of disease severity. We found no variation in percentage of mFas-bearing mononuclear cells; high and unchanging levels of Fas mRNA and protein, and high and invariable sFas values. Overproduction of sFas antagonises mFas function and plays a role as a decoy in the peritoneal fluid. The mFasL-bearing mononuclear cells and protein levels decreased from the minimal to the severe stage of disease. In contrast to FasL protein, FasL mRNA was overexpressed throughout the course of the disease. sFasL values were high and increased as the disease worsened. Our results showed a non-linear ratio between FasL mRNA and FasL protein levels. Abnormally elevated FasL mRNA may be due to dysregulation in several mechanisms controlling mRNA turnover. The high level of sFasL would be expected to down-regulate FasL activity and compete with the membrane form for mFas binding. As a consequence, mFas-bearing mononuclear cells may be unable to kill and in turn, may themselves become targets for killing by FasL-expressing endometriotic cells.

Relationship between circulating soluble Fas ligand and preexisting left ventricular hypertrophy in the setting of left ventricular remodeling after acute myocardial infarction

We aimed to investigate the effects of preexisting left ventricular hypertrophy (LVH) on the circulating concentration of soluble Fas ligand (sFasL) and also the relationship of sFasL to ventricular remodeling in patients with acute myocardial infarction (MI). Forty consecutive patients who presented with their first episode of acute MI were studied. These patients were then divided into two groups with regard to the presence of LVH. All the patients underwent complete transthoracic echocardiography with determination of end diastolic volume index and LV mass index within 24 h and at 6 months. sFasL levels were determined in serum on admission and at 24 h of admission. The serum sFasL concentration did not change significantly after acute MI at 24 h after admission in the study population (P=0.574), however, the serum level of sFasL concentration was significantly increased in the patients with preexisting LVH (P<0.001). There was a strong positive relationship between LV mass index and the serum level of sFasL concentration at 24 h after admission (r=0.611; P<0.001). Moreover, there was a stronger correlation between the change in end-diastolic volume index at 6 months and the serum level of sFasL in the LVH group compared with the group without LVH (r=0.499 and 0.181, respectively). In conclusion, we have shown that serum sFasL concentration at 24 h after admission was significantly higher in patients with LVH, and also, there is a close relationship between the serum level of sFasL and LV enlargement.

Soluble Fas might serve as a diagnostic tool for gastric adenocarcinoma

BackgroundFas (Apo-1/CD95) and its specific ligand (FasL) are key elements in apoptosis. They have been studied in different malignancies but there are few published studies about the soluble forms of these markers (i.e. sFas/sFasL) in gastric cancer. We have compared the serum levels of sFas/sFasL in gastric adenocarcinoma patients and cases with pre-neoplastic lesions as potential markers for early diagnosis, and investigated their relation with clinicopathological characteristics.MethodsFifty-nine newly-diagnosed cases of gastric adenocarcinoma who had undergone gastrectomy, along with 62 endoscopically- and histologically-confirmed non-cancer individuals were enrolled in this study. sFas/sFasL serum levels were detected by Enzyme Linked Immunosurbent Assay.ResultsMean serum sFas level was significantly higher in gastric cancer patients than in control group (305.97 ± 63.71 (pg/ml) vs. 92.98 ± 4.95 (pg/ml), P < 0.001); while the mean serum level of sFasL was lower in patients with gastric adenocarcinoma (0.138 ± 0.04 (pg/ml) vs. 0.150 ± 0.02 (pg/ml), P < 0.001). Mean serum levels of sFas/sFasL were significantly different in both intestinal/diffuse and cardiac/non-cardiac subtypes when compared to the control group (P < 0.001). There was an increase in the serum level of sFas from the first steps of pre-neoplastic lesions to gastric adenocarcinoma (P < 0.001). Patients who had no lymph node involvement (N0) showed significantly higher serum levels of sFas compared to others (P = 0.044).ConclusionsProduction of sFas may play a critical role in the carcinogenesis of intestinal-type gastric cancer. sFas serum level may serve as a non-invasive tool for early diagnosis of gastric cancer.

Inhibition of NF-kappa B can enhance Fas-mediated apoptosis in leukemia cell line HL-60

This study explored the effects of nuclear factor-kappa B (NF-κB) inhibitor Bay 11-7082 on Fas/FasL system and Fas-mediated apoptosis in cell line HL-60 cells. The mRNA and protein levels of Fas, FasL, and X-linked inhibitor of apoptosis protein (XIAP) were detected by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry (FCM); the level of sFasL was evaluated by enzyme-linked immunosorbent assay (ELISA); and apoptosis was determined by FCM. After treatment with Bay 11-7082, the mRNA and protein levels of FasL and XIAP in HL-60 cells were significantly lower than in the controls (P<0.05), but the mRNA and protein levels of Fas and sFasL did not change significantly (P>0.05). Apoptotic rate of HL-60 cells treated with Bay 11-7082 was significantly higher than in the controls (P<0.05). Therefore, we conclude that Bay 11-7082 can enhance Fas-mediated apoptosis in HL-60 cells by downregulating FasL and XIAP levels.

Article Commentary: Fas and Cancer

Apoptosis is an active process of programmed cell death. Fas is a cell-surface protein which is expressed on activated lymphocytes and known as CD95, TNFRSF6 or APO-1. Fas-L is ligand of Fas and known as CD95 LG or TNFSF6. Apoptosis or cell death is a result of binding of Fas-L to Fas which is expressed on the surfaces of these cells. Cancer cells escape this binding by overexpression of Fas-L or down expression of Fas. Fas and Fas-L exist in membrane bound and soluble forms. The serum level of sFas and sFas-L can be evaluated by immunostaining, immunohistochemical methods, immunofluorescence, flow cytometry and Western blotting. Head and neck squamous cell carcinoma diagnosis, staging and prognosis can be evaluated early and accurately by sFas and sFas-L expression levels detection.

Correlation of Plasma Soluble Fas Ligand Levels with Severe Anaemia in Gabonese and Indian Plasmodium falciparum Malaria Patients

A comparative analysis of the plasma concentrations of soluble Fas-L (sFas-L) and their correlation with he- moglobin levels and malaria severity was carried out in cohorts of P. falciparum-infected patients from Gabon and India. Young patients from Gabon had plasma levels of sFas-L that increased with disease severity. In contrast, in Indian adults plasmatic sFas-L levels were more elevated in UM and SNCM than in CM. In both Gabonese and Indian subjects, sFas-L concentrations were negatively correlated with haemoglobin rates, which were lower in SNCM than in UM or CM in both populations. We also observed a positive correlation between the level of plasmatic sFas-L with the level of circulating IL-2 receptor in the Indian patients. All these observations suggest a paradoxical role of sFas-L in CM pathogenesis when comparing Gabonese and Indian patients, while a similar role was found to be associated with severe anaemia.

Increased Soluble Fas and Fas Ligand Levels in Patients with Nonalcoholic Steatohepatitis

Purpose: To test the association of death receptor proteins soluble FAS (sFAS) and soluble FAS Ligand (sFASL) with nonalcoholic steatohepatitis (NASH) independent of known confounders and their correlation with disease severity and insulin resistance. Methods: Plasma sFAS and sFASL were measured using a sandwich ELISA based immunoassay in 70 patients undergoing liver biopsy with clinical suspicion of NAFLD. Histology was assessed in a blinded manner and the NAFLD activity score was calculated for each sample. In parallel sFAS and FASL levels were measured in patients with Hepatitis C (validation set) and the levels in hepatitis C patients were compared with sFAS and sFASL levels in NASH patients. Results: Of the 70 study subjects,37 patients had NASH, 20 had steatosis and 13 normal liver biopsy. Mean age was 49 (±11) years, 45.7% were male and 84% Caucasians. The mean body mass index (BMI) was 31.7 (±4.9) kg/m2 and the median triglycerides and HOMA index were 158 (94–210) mg/dL and 3 (1–7.4) respectively. Patients with NASH had significantly higher levels of both sFAS and sFASL than patients with steatosis and normal liver biopsy (Table 1). NASH patients had significantly higher level of sFASL than Hepatitis C patients (Table 1). sFAS and sFASL showed strong positive correlation with degree of fibrosis (r = 0.499 and 0.315, P < .001 and P= .008 respectively). Positive correlation was also seen between sFAS and HOMA (r = 0.336, P= .007). On multivariate analyses, a 10 pg/ml increase in sFASL increased the odds of having NASH by 60% 1.6 (1.04–2.5, P= 0.034); a 1 ng/ml increase in sFAS levels increased the odds by 40% 1.4 (1.2–1.6, P= 0.003) and a 10 IU/L increase in liver enzymes showed only a 20% increase in the odds of having NASH 1.2 (1.00–1.4, P= 0.093) (Table 2).Table 2: Prognostic value of sFAS and sFASL in prediction of NASHTable 1: sFAS and sFASL levels are highest in patients with NASHConclusion: The data implicates a significant role for sFAS/sFASL interaction in NAFLD progression. This concept merits further investigation as a potential diagnostic and therapeutic strategy.

Seasonal changes of proapoptotic soluble Fas ligand level in allergic rhinitis combined with asthma

The function of apoptosis is to eliminate unnecessary or dangerous cells. The balance between production and death is important in the control of cell numbers within physiological ranges. Cells involved in allergic reactions may have altered apoptosis. The aim of this study was to examine the seasonal changes of programmed cell death in children with pollen allergy. We measured serum levels of soluble Fas (sFas) and soluble Fas ligand (sFasL), and examined whether there was any correlation between soluble apoptosis markers and development of asthma and or rhinitis in children with pollen allergy. We examined two groups of patients with ragweed pollen allergy. The first group consisted of 17 children with 'rhinitis only'. The second group consisted of 16 children with 'asthma + rhinitis'. For seasonal analysis we pooled the two groups and termed this the 'ragweed sensitive' group (n = 33, 5-18 yr, 25 boys, eight girls). Measurements (sFas and sFasL) were taken during the ragweed pollen allergy season, while control measurements were performed during the symptom-free period. There was no difference in sFas levels measured during and after [1941 +/- 68, 1963 +/- 83 pg/ml (mean+/-s.e.m, respectively)] the pollen season in the 'ragweed sensitive' group. The sFasL level showed seasonal change, which was significantly higher (p = 0.0086) in the symptomatic period compared to the symptom-free state (99 +/- 13 and 53 +/- 16 pg/ml, respectively). There was a difference between the 'rhinitis only' and the 'asthma + rhinitis' groups in the measured parameters of apoptosis. Children having allergic rhinitis combined with asthma had a significantly (p = 0.03) higher sFas level in the symptom-free state than the 'rhinitis only' group did (2115 +/- 156 and 1820 +/- 52 pg/ml, respectively). During the allergic symptom state the sFasL level of the 'asthma + rhinitis' group was significantly higher (p = 0.025) than that of the 'rhinitis only' group (125 +/- 20 and 75 +/- 14 pg/ml, respectively). In conclusion, the increased level of sFasL during the pollen season may signal its role in the pathogenesis of allergic airway diseases. There was no seasonal change in sFas levels in the examined ragweed allergic group, however in the symptomatic period we observed a diminished level of antiapoptotic factor (sFas) and an elevated level of proapoptotic factor (sFasL) if there was a combined disease with pollen allergic asthma. We suggest that there is a deviation in the apoptotic reaction in children that may increase the seasonal allergic inflammation.

Role of soluble Fas ligand in autoimmune diseases.

To investigate the role of soluble Fas ligand in autoimmune diseases. RT-PCR was performed to amplify sFasL cDNA from the total RNA extracted from activated human peripheral blood lymphocytes. DNA fragments were cloned into PCR vector. After sequenced, sFasL gene fragments were inserted into pQE-31 vector and expressed in E. Coli M15 respectively. Proteins were purified through affinity chromatography column with ligand of 6XHis tag and identified by SDS-PAGE and Western blot. Mice were immunized with sFasL protein and specific anti-serum was harvested 6 wk after immunization. Monoclonal anti-human FasL antibody was made from the immunized mice. Serum level of sFasL in different patients was detected using anti-FasL antibodies from the immunized mice. The protein expressed was 24 ku by SDS-PAGE electrophrosis. The protein was specially bound to anti-human FasL antibody by Western blot analysis. The sFasL protein could induce Jurket cell apoptosis in vitro. The concentration of serum sFasL in patients with autoimmune diseases was higher than that in normal individuals. sFasL could reduce arthritis in collagen induced arthritis (CIA) mice model by subcutaneous injection. sFasL may be involved in either induction of apoptosis or autoimmune diseases. Furthermore, sFasL may have potential application in treatment of autoimmune diseases.

Significance of serum soluble fas ligand in patients with bladder carcinoma

Objective To study the significance of serum soluble Fas ligand in patients with bladder carcinoma. Methods Sandwich enzyme linked immuno-sorbent assay (ELISA) was used to detect the level of sFasL in sera of 48 bladder carcinoma patients and 25 healthy donors. Results The level of sFasL in patients with bladder carcinoma pre-operation was 12.25 ± 1.16 μg/L. It was higher than that in patients after operation and that in healthy donors( P 0.05 ). The level of serum sFasL in patients with muscle-invasive bladder carcinoma(T_ 2～4 ) was higher than that in patients with superficial bladder carcinoma (T_ 0～1 ) ( P 0.05 ); The serum level of sFasL in patients with bladder carcinoma in grade 3 was higher that in grade1 and grade 2 bladder carcinoma respectively ( P 0.05 ). Conclusion Serum sFasL is correlated with both disease progression and increase in the tumor grade of bladder carcinoma.

Dysregulation of apoptosis in scorpion envenomed children: its reflection on their outcome

In the present study, 46 children in Upper Egypt (less than 13 years old) were admitted to the Pediatric Intensive Care Unit for scorpion envenomation. They were compared with 20 apparently healthy children of matching age and sex as controls. Out of the studied victims, 25 children (54%) showed signs of severe envenomation and multiple organ dysfunction (MOD), while 21 victims (46%) showed signs of mild envenomation. The serum levels of apoptotic markers, soluble Fas (sFas), soluble Fas ligand (sFasL) and Bcl-2, were determined for both victims and controls. In addition, the serum levels of nitric oxide (NO) and lipid peroxides (LPO) were also measured. Scoring of MOD was evaluated using Logistic Organ Dysfunction System Score (LODS) for the severely envenomed victims. All victims (both severe and mild cases) showed significantly higher mean levels of sFas, LPO and NO and significantly lower serum levels of Bcl-2 in comparison to the controls. The level of sFasL was not detectable in the sera of the healthy control group. The case fatality rate was 15%. The severely envenomed children with MOD as well as the non-survivors showed significantly higher serum levels of sFas, sFasL, LPO and NO and significantly lower serum levels of Bcl-2 in comparison to the mild envenomed victims and the surviving victims of severe cases, respectively. The LODS score of the severely envenomed victims showed significant positive correlations with sFas and LPO and significant negative correlation with Bcl-2. In all victims, a significant positive correlation was detected between sFas and NO. On the other hand, Bcl-2 was significantly negatively correlated with both sFas and LPO. In conclusion, our study revealed that scorpion envenomation can increase apoptosis as shown by up-regulation of sFas/sFasL system and down-regulation of Bcl-2 that was associated by elevation of LPO and NO. This dysregulation of apoptosis was increased with the severity of scorpion envenomation and its extent increased as MOD score and outcome increased. Therefore, sFas and Bcl-2 may be of value in predicting the outcome of these cases. The increase of the extent of apoptosis detected in this study seems to play a role in the outcome of scorpion envenomation, and hence, should be taken into consideration for strategies of therapeutic regimen.

Effect of clotting factors concentrates on lymphocyte and neutrophil function in vitro

SummaryImmunological abnormalities have been reported in haemophiliacs. Although infections with HIV, hepatitis and other viruses may contribute to these abnormalities, immune defects are detectable also in HIV seronegative haemophiliacs. It is likely that chronic exposure to extraneous proteins in clotting factor concentrates (CFCs) may play a role in immunomodulation, but the underlying mechanisms remain unclear. The results of the present paper show that: a) soluble HLA class I (sHLA-I), soluble Fas-ligand (sFas-L) and transforming growth factor beta 1 (TGF-β1) are detectable in plasma derived but not in recombinant CFCs; b) the level of sHLA-I and sFas-L is proportional to the grade of CFCs purity whereas TGF-β1 showed very variable levels; c) soluble molecules detected in CFCs exert immunomodulatory effects in vitro like apoptosis induction in Jurkat cells and inhibition of mixed lymphocyte reaction response, antigen-specific lymphocyte cytotoxic activity and neutrophil chemotaxis.

Prognostic significance of a combination of soluble Fas and soluble Fas ligand in the serum of patients with Ta bladder cancer.

Recurrence after transurethral resection is one of the major problems in the treatment of superficial bladder cancer. However, there are no potent prognostic markers for recurrence in superficial bladder cancer at present. As circulating soluble Fas (sFas) and soluble Fas ligand (sFasL) have been implicated in protection from Fas-mediated apoptosis against cancers and may interfere with immune surveillance against autologous cancers, sFas and sFasL in the serum of patients with Ta bladder cancer were evaluated as prognostic tumor markers for recurrence. The serum levels of sFas and sFasL were measured by an enzyme-linked immunosorbent assay. Patients with Ta bladder cancer with low serum levels of both sFas and sFasL had a significantly longer postoperative tumor-free interval than those with high serum level of either sFas or sFasL in the 3-year follow-up. There was no correlation between the serum levels of sFas and sFasL. The present study has demonstrated that elevated serum sFas or sFasL predicts early recurrence in patients with Ta bladder cancer. These findings suggest that the serum levels of sFas and sFasL can be used as a prognostic indicator for recurrence in patients with Ta bladder cancer, and that sFas and sFasL may independently inhibit Fas-mediated apoptosis.

Significance of serum soluble Fas ligand in patients with bladder carcinoma.

The interaction of Fas and Fas ligand (FasL) plays an important role in cytotoxic T-lymphocyte-mediated and natural killer cell-mediated apoptosis against tumor cells. Circulating soluble FasL (sFasL) has been suggested to provide protection from Fas-mediated apoptosis. The current study examined this possibility in patients with bladder carcinoma. The levels of sFasL in the serum of 163 patients with bladder carcinoma were determined using an enzyme-linked immunoadsorbent assay. Antiautologous tumor cytotoxic activity was assessed by the 12-hour chromium isotope ((51)Cr) release assay. The mean serum level of sFasL in patients with bladder carcinoma was 2.5-fold higher than that in healthy donors. The level of serum sFasL in patients with muscle-invasive bladder carcinoma was 2.5-fold higher than that in patients with superficial bladder carcinoma. In addition, serum sFasL levels in patients with T1 and Tis bladder carcinoma was 2-fold and 2.7-fold higher, respectively, than levels in patients with Ta bladder carcinoma. The serum level of patients with sFasL in Grade 3 bladder carcinoma were 2.4-fold and 1.7-fold higher than that in patients with Grade 1 and Grade 2 bladder carcinoma, respectively. Patients with Ta bladder carcinoma with a low level of serum sFasL (less than the median value) had a longer postoperative tumor-free interval than patients with a high sFasL level (greater than the median value) in the 5-year follow-up. There was an apparent inverse correlation between the level of serum sFasL and antiautologous tumor cytotoxic activity. The results of the current study demonstrated that the level of serum sFasL is correlated with both disease progression and increase in the tumor grade, and that an elevated serum sFasL level predicted early recurrence in patients with Ta bladder carcinoma. These findings suggest that elevated serum sFasL levels might be associated with a greater risk of disease progression and recurrence in patients with bladder carcinoma.