Serum Levels Of Stem Cell Factor Research Articles

Elevated cutaneous expression of stem cell factor in chronic spontaneous urticaria: a prospective cohort study.

Tissue expression of endothelial cell (EC) markers of microcirculatory changes in CSU is poorly investigated. to explore the expression of specific EC markers (stem cell factor (SCF), vascular endothelial growth factor (VEGF) and membrane attack complex (MAC)) in CSU-L and CSU-NL skin through immunohistochemistry (IHC) and in serum. Lesional (L) and non-lesional (NL) skin biopsies from CSU patients and HCs were studied for the IHC expression of SCF, VEGF and MAC in CSU patients (n = 23) and healthy controls (HCs, n = 9). In this population, we also investigated blood levels of VEGF and SCF. Patients were also assessed for clinical characteristics, disease activity, and markers of autoimmune CSU (aiCSU). Epidermal SCF reactivity was significantly higher in CSU-L skin compared to HC skin (p=0.026). In the dermis, SCF immunoreactivity was seen particularly on endothelial, perivascular and epithelial cells. In CSU-L skin, mean perivascular SCF stainings were significantly more intense compared to HCs (p<0.001). Furthermore, CSU-NL skin also showed significantly higher SCF stainings on dermal perivascular cells compared to HCs (p<0.001). CSU patients had the highest SCF immunoreactivity scores in the epidermis and/or on dermal ECs. These patients did not have significantly higher SCF serum levels. This is the first study to show elevated cutaneous expression of SCF in chronic spontaneous urticaria. These findings underline the potential therapeutic possibilities of anti-KIT antibodies in CSU treatment.

Modified Taohong Siwu decoction improves cardiac function after myocardial ischaemia and reperfusion in rats by promoting endogenous stem cell mobilization and regulating metabolites

Context Taohong Siwu decoction (THSWD) has been shown to promote heart repair in myocardial infarction. Objective To determine the effects of modified THSWD (THSWD plus four ingredients) on myocardial ischaemia and reperfusion (I/R) injury. Materials and methods Sixty Sprague-Dawley rats were randomly divided into the I/R group and three different modified THSWD dose groups (gavage administration, 1.215, 2.43, and 4.86 g, respectively). 2,3,5-Triphenyltetrazolium chloride and Evans blue staining were used to detect the infarct area at 24 h after treatment. The serum biochemical indexes and cell apoptosis were examined to determine myocardial injury. The number of endogenous stem cells, expression of stromal dell derived factor-1 (SDF-1) and stem cell factor (SCF), and cardiac function were measured at 4 weeks. The serum was collected for metabolomic analysis. Results The high-dose modified THSWD group presented a reduced infarction area (decreased by 21.3%), decreased levels of lactate dehydrogenase and creatinine kinase, attenuated cell apoptosis, and enhanced superoxide dismutase activity in early stage I/R compared with other groups. The serum SCF and SDF-1 levels were higher in the high-dose group than in the I/R group. At 4 weeks, the infarct size and collagen content were the lowest, and the ejection fraction and fractional shortening values were the highest in the high-dose group. Moreover, high-dose modified THSWD affected the metabolism of phosphonate and phosphonate, taurine, and hypotaurine. Conclusions Endogenous stem cell mobilization and metabolic regulation were related to the cardioprotection of modified THSWD. We provided a new strategy and direction for the treatment of cardiovascular diseases with traditional Chinese medicine.

Serum Levels of Granulocyte-Macrophage-colony-stimulating Factor and Stem-cell Factor During Liver Regeneration after Partial Hepatectomy in Humans.

Multiple biological functions have been recognized regarding Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) and Stem Cell Factor (SCF). To evaluate the serum changes of GM-CSF and SCF in patients undergoing surgical resection for liver tumor, in the regenerative phase after surgery in order to identify the possible relationship with the patient, tumor or surgical variables. Thirty-two consecutive patients (50% male, median age 66), undergoing hepatic resection of liver neoplasm, were evaluated. The liver tumor was Hepatocellular Carcinoma (HCC) in 44% of cases. Other tumors were cholangiocarcinoma and metastasis. Serum levels of GM-CSF and SCF were assessed at baseline and 2 days, 7 days and 4 weeks after surgery. Personal and clinical patient data were also recorded. The statistical analysis was carried out using t-test for unpaired data or ANOVA (repeated measure) for continuous variables and Fisher test for discrete variables. GM-CSF levels remained constant after surgery and were compared to baseline values. SCF levels, on the other hand, increased during the time, after surgery. The evaluation of SCF levels (fold increase) according to surgical, patient and tumor variables evidenced some differences. At day 7 and week 4, SCF levels were statistically increased: i) in patients undergoing a large resection in comparison with others (p<0.05); ii) in patients non-cirrhotic in comparison with cirrhotic ones (p=0.02) and finally; iii) in patients with non-HCC tumor in comparison with HCC ones (p=0.02). During liver regeneration in humans, SCF serum levels are increased allowing to hypothesize a possible role of this chemokine during tissue growth and remodeling.

Serum Stem Cell Factor Level Predicts Decline in Kidney Function in Healthy Aging Adults.

Stem cell factor (SCF), the ligand of the c-kit receptor, actively participates in the organ reconstruction and fibrosis associated with various diseases, including kidney disease. However, it remains unclear whether SCF plays a role in kidney aging. In the present study, we measured the serum SCF level, estimated glomerular filtration rate (eGFR), and other biological parameters in a Chinese Han group of 892 subjects, and explored the relationship between SCF level and renal function during aging; we sought to define novel biomarkers of kidney aging. Multiple linear regression was used to select potential indicators of decline in renal function. Only age, SCF level, and 25% maximum expiratory flow (25% MEF) were significant predictors after redundancy analysis (|r| > 0.70 and P < 0.05). Multiple linear regression showed that the relationship among eGFR, SCF level, and age could be described as follows: eGFR = 154.486 - (0.846 × age) - (0.011 × SCF level). We found no between-gender difference in the effect of SCF on kidney aging. In conclusion, the SCF level is an ideal biomarker of renal aging and may help to predict changes in eGFR during aging.

Serum level of stem cell factor and its soluble receptor in aspirin-exacerbated respiratory disease

Aim: Stem cell factor (SCF) may be associated with inflammatory processes leading to aspirin-induced asthma. This study evaluated the relationship between serum level of SCF and its soluble receptor with aspirin-induced asthma. Methods & materials: Twenty-five patients and 25 healthy controls were enrolled in this study. The concentration of SCF and mast/stem cell growth factor receptor (C-kit) was determined in serum samples. Spirometry and rhinometry were performed to determine the severity of the disease. p < 0.05 were considered significant. Results: The serum levels of SCF and C-kit receptor were significantly higher in the case group. The serum SCF and C-kit level had a significant positive correlation with the severity of asthma, disease duration and nasal obstruction. Conclusion: Our findings suggest that SCF and C-kit receptors have a direct effect on the severity of aspirin-induced asthma.

Role of stem cell factor in the regulation of ICC proliferation and detrusor contraction in rats with an underactive bladder.

Stem cell factor (SCF) is critical in regulating the proliferation, differentiation and function of the interstitial cells of Cajal (ICCs), which are closely associated with smooth muscle dysfunction. The present study aimed to examine the effect of SCF on ICC proliferation and detrusor contraction in rats with an underactive bladder. Sprague-Dawley rats were divided into four groups comprising control, control+SCF, detrusor underactivity (DU), and DU+SCF groups. The ICC count was determined using immunofluorescence; serum levels of SCF were determined using an enzyme-linked immunosorbent assay; mRNA and protein levels of c-kit and SCF in tissues were assessed using reverse transcription-quantitative polymerase chain reaction and western blot analyses, respectively. Detrusor contractility was determined using muscle strips, based on the contraction amplitude and frequency determined in each specimen. Significantly fewer ICCs were observed in the DU group, in addition to decreased expression levels of SCF and c-kit, compared with the control group. In addition, the detrusor contraction frequency and amplitude were markedly reduced. However, the administration of SCF significantly increased the number of ICCs, and the levels of SCF and c-kit in animals with DU, and resulted in markedly amplified detrusor contraction frequency and amplitude. Similarly, the number of ICCs and levels of SCF and c-kit were higher in the control+SCF group, compared with the control group. Overall, these findings suggested that exogenous SCF improved the organ dysfunction caused by reduced ICC number, providing a novel approach for organ repair.

Yangyin Runchang Decoction Improves Intestinal Motility in Mice with Atropine/Diphenoxylate-Induced Slow-Transit Constipation.

This study assessed the efficacy and mechanism of action of Yangyin Runchang decoction (YRD) in the treatment of slow-transit constipation (STC). ICR mice were randomly divided into four groups (n = 10/group) and treated with saline (normal control; NC), atropine/diphenoxylate (model control; MC; 20 mg/kg), or atropine/diphenoxylate plus low-dose YRD (L-YRD; 29.6 g/kg) or high-dose YRD (H-YRD; 59.2 g/kg). Intestinal motility was assessed by evaluating feces and the intestinal transit rate (ITR). The serum level of stem cell factor (SCF) and changes in interstitial cells of Cajal (ICCs) were also evaluated. Additionally, the expression of SCF and c-kit and the intracellular Ca2+ concentration [Ca2+]I were investigated. Fecal volume and ITR were greater in the L-YRD and H-YRD groups than in the MC group. The serum SCF level was lower in the MC group than in the NC group; this effect was ameliorated in the YRD-treated mice. Additionally, YRD-treated mice had more ICCs and elevated expression of c-kit and membrane-bound SCF, and YRD also increased [Ca2+]I in vitro in isolated ICCs. YRD treatment in this STC mouse model was effective, possibly via the restoration of the SCF/c-kit pathway, increase in the ICC count, and enhancement of ICC function by increasing [Ca2+]i.

Increasing Numbers of Mast Cells in Skin Lesions of Hyperpigmented Mycosis Fungoides with Large-Cell Transformation.

Dear Editor: Mycosis fungoides (MF) is a common type of cutaneous T-cell lymphoma. In recent years, several reports have been published on an uncommon and rare form of MF: hyperpigmented MF1,2,3,4. Herein, we report a case of hyperpigmented MF and discuss the mechanisms of hyperpigmentation. A 55-year-old Japanese man presented at the dermatological outpatient clinic of our hospital for widespread, pruritic, hyperpigmented plaques. The lesions, which first appeared nearly 15 years ago, gradually developed; they were diagnosed as MF, and were subsequently treated with topical corticosteroids and/or radiation with narrow-band ultraviolet B (UVB). However, no therapeutic response was observed and small nodular lesions developed. On physical examination of the patient, we observed hyperpigmented plaques with no atrophy on the face, trunk, and extremities (Fig. 1A). We found small nodules on the back. Blood cell count, urinalysis, and serum chemistry were within normal limits. Anti-human T-cell leukemia virus type I antibody was negative. Computed tomography scan from the neck to the pelvic area was normal. Histopathological analysis of skin specimens collected from a hyperpigmented plaque on the buttocks revealed slight acanthosis with atypical lymphocytic infiltration within the epidermis and upper dermis, containing some inflammatory cells and abundant melanophages (Fig. 1B). Rearrangement of the T-cell receptor (β chain) was detected using reverse transcriptase polymerase chain reaction method, but not Southern blot analysis. Immunohistochemically, most of the atypical lymphoid cells were CD4-positive (Fig. 1C and D). We diagnosed the lesions as MF, particularly, hyperpigmented MF. After X-ray irradiation to the nodules on the back, oral retinoid plus long-wave UVA therapy was started. Although CD30 (+) large-cell transformation was found during the therapeutic course, the patient's general health and skin improved over time. Fig. 1 (A) Clinical manifestation. Hyperpigmented plaques on the trunk. (B) Histology of the lesional skin of a hyperpigmented plaque. Slight acanthosis with atypical lymphocytic infiltration within the epidermis and upper dermis, containing abundant melanophages ... So far, the etiology of hyperpigmentation in certain MF cases is not clear. Pavlovsky et al.4 reported that hyperpigmented MF was characterized by a predominantly CD8-positive phenotype. Those authors speculated that CD8-positive tumor cells could have stronger cytotoxicity and affect neighboring cells such as melanocytes or basal keratinocytes, thereby causing interface changes and marked melanin incontinence, leading to the clinical appearance of hyperpigmentation4. However, in the present case, CD4-positive cells were dominant; therefore, hyperpigmentation cannot be attributed to this hypothesis. Yamamoto et al.1 reported the association of mast cell number with hyperpigmented MF. Melanocytes are strongly stimulated by stem cell factor (SCF), which also activates the mast cells. Increasing numbers of mast cells in the skin with lesions and an upregulation of SCF in sera of hyperpigmented MF cases were found1. Thus, we compared the numbers of mast cells in the skin with lesion with normal skin controls and non-pigmented MF cases. Mast cell counts were averaged from three random fields (cells/high-power field) in toluidine blue-stained skin specimens (Fig. 1E). As shown in Table 1, compared with normal and non-pigmented MF skin, the numbers of mast cells clearly increased in skin lesions of hyperpigmented MF. Unfortunately, we did not examine the serum levels of SCF. However, the increasing numbers of mast cells suggest the existence of similar underlying mechanisms as reported by Yamamoto et al.1 Table 1 Mast cell counts in skin

Effects of loratadine and cetirizine on serum levels of neuropeptides in patients with chronic urticaria.

H1-receptor inhibiting drugs, namely loratadine and cetirizine, were frequently used in treatment of chronic urticaria. Urticarial weal and flare reactions, a neurogenic reflex due to neuropeptides, were reported to be more effectively inhibited by cetirizine than loratadine. The aim of this study was to determine and compare the effects of systemic loratadine and cetirizine treatments on serum levels of selected neuropeptides in chronic urticaria. Treatment groups of either systemic loratadine or cetirizine (10 mg/d), consisting of 16 and 22 patients, respectively, were included. Serum levels of stem cell factor (SCF), neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), nerve growth factor (NGF), vasoactive intestinal peptide (VIP), and substance P (SP) were detected before and after one week of treatment with antihistamines. Serum NPY and VIP levels were significantly decreased when compared before and after treatment with antihistamines (P < 0.001 and P < 0.01, respectively). SCF and NGF values were also decreased after antihistamine treatment (P < 0.05). Post-treatment levels of CGRP were significantly higher compared with pretreatment values, while no significant difference was detected between pre and post treatment levels of SP. Cetirizine was significantly more effective than loratadine on lowering serum levels of SCF among the other neuropeptides. Systemic loratadine and cetirizine treatments in patients with chronic urticaria precisely caused variations in serum levels of neuropeptides. The predominant effect of cetirizine compared to loratadine on reducing serum SCF levels might be explained with anti-inflammatory properties of cetirizine.

Effect of ovarian stimulation with recombinant follicle-stimulating hormone, gonadotropin-releasing hormone agonist and antagonists, on follicular fluid stem cell factor and serum urocortin 1 levels on the day of oocyte retrieval

To compare the serum and follicular fluid (FF) concentrations of stem cell factor (SCF) as well as the serum urocortin 1 (UCN1) concentration in gonadotropin-releasing hormone antagonist (GnRH-ant) and gonadotropin-releasing hormone agonist (GnRH-a) protocols for controlled ovarian hyperstimulation (COH) in IVF patients. Follicular fluids and blood samples of 42 infertile women undergoing COH for IVF-embryo transfer with either GnRH agonist (n = 22) or GnRH antagonist (n = 20) protocols from 2010 to 2011 were collected during oocyte retrieval. SCF concentrations of serum and FF were assessed by sandwich enzyme immunoassay using ELISA Kit for SCF kid. Serum UCN1 concentration were measured using commercially available enzyme-linked immunosorbent assay. Concentrations of serum UCN1, serum and FF SCF were similar in the two groups. The serum SCF levels correlated strongly with the follicular SCF levels (r = 0.770, p < 0.001). The mean implantation rate, biochemical and clinical pregnancy rate and live birth rate per cycle were also similar in the groups. These observations suggest that there is no significant difference in follicular microenvironment in terms of SCF and UCN1 between agonist and antagonist protocols.

PTU-110 Circulating Bone Marrow-Derived Stem Cells and Stem Cell Factor Serum Level in Chronic Hepatitis C: Relation to Hepatic Proliferation and Fibrosis

IntroductionBone marrow-derived stem cells (BMSCs) are pluripotent cells that can be mobilised into circulation and recruited to sites of inflammation where they promote local tissue repair. Therefore, the present work...

Modulation of the Serum Cytokine Expression Pattern in Hymenoptera Allergic Patients Treated with Specific Venom Immunotherapy

Venom immunotherapy (VIT) is an adequate model to explore the immune mechanisms underlying this type of treatment. We have investigated the use of protein arrays to detect variations in the levels of cytokines in patients receiving VIT. In the present study we selected 11 non-atopic patients with systemic reactions after Hymenoptera sting that received VIT during at least three years. In order to evaluate the success of VIT all of them should have tolerated a sting field after VIT. Serum samples were obtained before initiating VIT and after at least three years of successful VIT. We analyzed 42 serum proteins corresponding to a Th1/Th2 panel using protein array methodology. We observed a significant increase of Interleukin 10, Myeloid Macrophage Colony Stimulation Factor, Macrophage Derived Chemokine, Interleukin 1- , Vascular Endothelial Growing Factor and Stem Cell Factor serum levels after successful VIT. We discuss the usefulness and normalization of this array method to analyze cytokines and other serum proteins. Monitoring these serum cytokines could help to predict the response and to elucidate the mechanisms underlying immunotherapy.

Serum hematopoietic growth factors as diagnostic and prognostic markers of acute renal allograft rejection: A potential role for serum stem cell factor

ObjectivesHematopoietic growth factors (HGFs) are proliferative and chemotactic agents for hematopoietic stem cells, although their functions on renal transplantation are rarely reported. This study aimed to investigate the association of HGFs with acute T cell-mediated renal rejection. Experimental designA cytokine bead array was used to analyze 10 HGFs in the sera of 32 patients with acute T cell-mediated renal allograft rejection before and during rejection and after rejection reversal. Stable renal allograft recipients (n=38) were also investigated. ResultsSerum levels of stem cell factor (SCF), IL-3, flt3 ligand, G-CSF, M-CSF and GM-CSF were elevated during episodes of rejection compared with before and after rejection. Serum concentrations of SCF, G-CSF, flt3 ligand and IL-3 were significantly higher than in the absence of rejection. Moreover, serum SCF levels were significantly higher in patients before rejection versus stable controls. ConclusionsHGFs are reported to be involved in acute T cell-mediated renal allograft rejection. A direct correlation was observed between SCF levels and the occurrence of acute renal allograft rejection which may represent an effective diagnostic and predictive biomarker for acute cellular renal allograft rejection.

Serum Stem Cell Factor Level in Renal Transplant Recipients With Posttransplant Erythrocytosis

The etiology of posttransplant erythrocytosis (PTE) remains unclear, and the most frequently suggested causative factors are still a matter of controversy. We aimed to investigate serum-soluble stem cell factor (sSCF) along with serum erythropoietin (EPO) levels in renal transplant recipients (RTRs) with PTE. Thirteen RTRs with PTE, 42 RTRs without PTE, and 42 healthy controls were included. Serum sSCF and EPO levels were determined using an enzyme-linked immunosorbent assay kit. Expected and observed/expected EPO levels were calculated. Serum sSCF levels and observed/expected EPO were significantly higher in RTRs with PTE than both RTRs without PTE and controls. In RTRs with PTE, sSCF level was significantly correlated with hematocrit and observed/expected EPO, respectively. Significant correlation was also observed between hematocrit level and observed/expected EPO in RTRs with PTE. Increased sSCF level and inadequate suppression of EPO production seem to have a role in the pathogenesis of PTE.

Elevation of serum stem‐cell factor in postoperative biliary atresia

Biliary atresia (BA) is one of the most common causes of neonatal cholestasis. Stem-cell factor (SCF) has been implicated in the development of fibrosis in various diseases. The objective of the present study was to examine the significant role of SCF in BA. Fifty-seven pediatric patients with BA after Kasai operation and 30 healthy children were recruited. The mean ages of BA patients and controls were 6.1 +/- 0.6 years and 6.1 +/- 0.7 years, respectively. The patients were categorized into two groups according to their serum levels of total bilirubin (TBil < 2 mg/dL, no jaundice vs TBil > or = 2 mg/dL, persistent jaundice) and alanine aminotransferase (ALT < 100 vs ALT > or = 100 U/L). The serum SCF levels were determined on commercially available enzyme-linked immunosorbent assay. The mean serum SCF level of the BA children was higher than that of normal controls (748.3 +/- 17.9 pg/mL vs 582.2 +/- 17.3 pg/mL; P < 0.001). Subsequent analysis demonstrated that the BA patients with serum ALT > or = 100 U/L had significantly greater levels of serum SCF compared to those with serum ALT < 100 U/L (796.5 +/- 22.6 pg/mL vs 694.7 +/- 25.0 pg/mL, respectively; P = 0.002). In addition, serum SCF levels were significantly elevated in the patients with portal hypertension (PH) compared with those without PH (810.0 +/- 18.8 pg/mL vs 634.1 +/- 20.1 pg/mL, P < 0.001). The current study showed that BA patients had higher serum SCF levels compared with controls. The significant elevation in SCF levels is associated with the presence of PH and the degree of hepatic injury. These findings suggest that SCF may play a part in the pathogenesis of hepatic fibrosis in BA patients after Kasai procedure.

Serum levels of stem cell factor and thrombopoietin are markedly decreased in fulminant hepatic failure patients with a poor prognosis

Hematopoietic growth factors including stem cell factor (SCF), thrombopoietin (TPO) and granulocyte colony stimulating factor (G-CSF) have a potential role in inducing bone marrow hematopoietic stem cells to move into the circulation, and the association of these factors with liver regeneration has received a lot of attention recently. The aim of this study was to determine the serum levels of such factors in patients with acute liver injury. The subjects were 25 patients with acute hepatitis (AH) who had a favorable prognosis and 26 patients with fulminant hepatitis (FH), of whom 11 were alive and 15 had died. Sixty-six healthy subjects matched for age and sex served as controls. Serum samples were collected before treatment, and the levels of SCF, TPO and G-CSF were measured using enzyme-linked immunosorbant assays. The levels of SCF and TPO were significantly lower in FH patients than in AH patients and the controls, and were also significantly lower in the FH patients who died, compared to the surviving patients. The G-CSF levels did not differ among them. These results suggest that low serum levels of SCF and TPO may be linked to poor prognosis in patients with severe liver injury.

Marked stem cell factor expression in the airways of lung transplant recipients

BackgroundAirways repair is critical to lung function following transplantation. We hypothesised that the stem cell factor (SCF) could play a role in this setting.MethodsWe studied 9 lung transplant recipients (LTx recipients) during their first year postgraft, and evaluated SCF mRNA expression in bronchial biopsy specimens using on-line fluorescent PCR and SCF protein levels in bronchoalveolar lavage (BAL) and serum using ELISA. The expression of SCF receptor Kit was assessed using immunostaining of paraffin-embedded bronchial sections.ResultsSCF mRNA was highly expressed during the early postgraft period [Month (M)1-M3] (300% increase vs controls: 356 vs 1.2 pg SCF/μg GAPDH cDNA, p < 0.001) and decreased thereafter (M4-M12: 187 pg/μg), although remaining at all times 10–100 times higher than in controls. While SCF protein levels in BAL were similar in LTx recipients and in controls, the SCF serum levels were at all times higher in LTx recipients than in controls (p < 0.05), with no relationship between these levels and the acute complications of the graft. Finally, Kit was strongly expressed by the mast cells as well as by the bronchial epithelium of LTx recipients.ConclusionSCF and Kit are expressed in bronchial biopsies from lung transplant recipients irrespective of the clinical status of the graft. A role for these factors in tissue repair following lung transplantation is hypothesised.

Stem Cell Factor (SCF) and Interleukin 3 (IL-3) in the Sera of Patients with Colorectal Cancer

For a long time markers that can detect a malignant cell transformation as early as possible have been sought. Substances which have been discovered are known as tumor markers. Stem cell factor (SCF) and interleukin 3 (IL-3) are members of a group of glycoprotein growth factors called hematopoietic cytokines (HCs). These factors take part in the regulation of developmental processes of hematopoietic progenitor cells and it was proved that HCs can be produced by different cancer cells, including colorectal cancer. The aim of this study was to investigate a potential role for SCF and IL-3 as tumor markers for colorectal cancer. We compared the serum levels of SCF and IL-3 in colorectal cancer patients with those in healthy subjects (control group) and commonly accepted tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9). We defined the diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and receiver-operating characteristics (ROC) curve of tested substances. SCF and IL-3 were determined using enzyme-linked immunosorbent assay (ELISA). CEA and CA 19-9 were measured by microparticle enzyme immunoassay. The serum levels of HCs and tumor markers were investigated in 75 patients with colorectal cancer and in 40 healthy subjects. There were significant differences in the level of circulating SCF and IL-3 in the colorectal cancer patients compared to the control group. Moreover, the diagnostic sensitivity of SCF was higher than the sensitivity of CEA and CA 19-9. The SCF area under the ROC curve was larger than the IL-3 area but smaller than the CEA and CA 19-9 areas. The diagnostic specificities of cytokines were lower than those of tumor markers, but the combined use of cytokines and tumor markers increased the diagnostic values. The highest values of diagnostic parameters were observed for the combined use of SCF and CA 19-9. These results suggest a potential role for SCF and IL-3 as tumor markers for colorectal cancer, especially in combination with CEA or CA 19-9.

Mechanism of angiopoietin-1 mediated endothelial progenitor cell recruitment in wound healing

Abstract Introduction: Gene transfer of Angiopoietin-1(Ang-1) corrects diabetic impaired wound healing by recruiting endothelial progenitor cells(EPCs) and enhancing neovascularization. EPCs are thought to be mobilized from the bone marrow through MMP9 activation of stem cell factor(SCF). We hypothesize that Ang-1’s effects on EPC recruitment are mediated through an MMP9 dependant-SCF activation mechanism. Methods: 8mm wounds were made in MMP9-/- or control mice. Wounds were treated with either 108PFU Ad-Ang-1(n=12), AdControl(n=12) or PBS(n=12). Half of MMP-9 -/- mice received daily intravenous SCF. Wounds at 7 days were analyzed for epithelial gap, capillary density(CD31), and EPCs(GATA-2). Serum SCF levels were assessed by ELISA. Letters in parentheses correspond to Table 1. Data expressed as mean+/-SEM. Results: Results: In control mice, Ang-1 had no effect on wound closure(a), neovascularization(b), or EPC recruitment(c). In MMP9-/- mice, AdAng1 accelerates reepithelialization(d)(p ∗ . Control MMP9 −/− MMP9 −/− IV SCF Ang1 Ad CTRL PBS Ang1 Ad CTRL PBS Ang1 Ad CTRL PBS Epithelial gap (mm) 2.7 ± 0.1 (a) 3.4 ± 0.2 (a) 2.6 ± 0.1 (a) 3.2 ± 0.1 ∗ (d) 4.1 ± 0.2 (d) 3.8 ± 0.2 (d) 2.7 ± 0.2 ∗ ∗ (g) 4.6 ± 0.4 (g) 4.5 ± 0.1 (g) Cap density (Caps/HPF) 7.5 ± 0.4 (b) 7.0 ± 0.4 (b) 7.0 ± 0.3 (b) 4.1 ± 0.5 (e) 3.9 ± 0.4 (c) 3.9 ± 0.6 (e) 8.4 ± 0.7 ∗ ∗ (h) 4.4 ± 0.4 (h) 4.6 ± 0.4 (h) EPCs (EPCs/HPF) 8.3 ± 0.2 (c) 7.3 ± 0.3 (c) 7.2 ± 0.2 (c) 2.0 ± 0.3 (f) 1.5 ± 0.3 (f) 1.6 ± 0.2 (f) 6.4 ± 0.3 ∗ ∗ (i) 2.4 ± 0.3 (i) 2.6 ± 0.2 (i) ∗ Indicates statistically significant differences (p Conclusions: Ang-1 mediated EPC recruitment and neovascularization occurs via an MMP-9 dependant activation of SCF mechanism. Ang-1 effects on reepithelialization are independent of this pathway. While SCF mobilizes EPCs, it has no effect on wound healing. SCF in combination with Ang-1 results in site specific recruitment of EPCs and enhanced neovascularization. EPC recruitment by Ang-1 is a novel and potentially potent therapeutic strategy to enhance impaired wound healing.

Circulating stem cell factor in patients with chronic idiopathic urticaria

The nature of histamine-releasing factors involved in the pathogenesis of chronic idiopathic urticaria (CIU) is still controversial, since functional IgG autoantibodies specific for the high-affinity IgE receptor, Fc(epsilon)RI, can be detected in only 20% of patients showing a strong skin reactivity on the autologous serum skin test. The absence of systemic eosinophilia in CIU patients, along with the increase in mast cells in skin biopsy specimens, suggests a possible role for stem cell factor (SCF), the only cytokine/growth factor known to induce mediator release from human mast cells. To investigate the possible role of SCF as a histamine-releasing factor in patients with CIU. The SCF levels were measured in serum samples from 65 patients with CIU who scored strongly positive on the autologous serum skin test; of these patients, 32 had negative results and 33 had positive results on in vitro histamine release assay by a quantitative commercial sandwich immunoassay technique. Serum samples from 40 healthy subjects were used as controls. Serum SCF levels in all 65 CIU patients did not differ from those found in healthy controls. No difference in SCF levels was found between patients with positive and negative results on histamine release assay. An increase in serum SCF levels does not play a pathogenic role in CIU.