Soluble c‐kit molecule in serum from healthy individuals and patients with haemopoietic disorders

Kawakita, Makoto; Yonemura, Ydji; Miyake, Hirosada; Ohkubo, Toshiya; Asou, Norio; Hayakawa, Kayoko; Nakamura, Mitsurd; Kitoh, Takashi; Osawa, H; Takatsuki, Kiyoshi; Suda, Toshio

doi:10.1111/j.1365-2141.1995.tb05239.x

Cited by 27 publications

(25 citation statements)

References 20 publications

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“…This median value of the controls is close to the one given by the manufacturer of the ELISA kit for healthy individuals (188 AU/mL Ϯ 57 AU/mL), and similar to the values found by Kawakita et al 29 No significant associations were found between patient age at the time of sampling, gender, and the pretreatment levels of serum KIT, SCF, VEGF, or whole-blood VEGF (P Ͼ .10 for all analyses). Serum VEGF levels were generally higher in patients with GISTs than in the control subjects (median, 303 pg/mL vs 190 pg/mL; P ϭ .013), whereas the pretreatment serum SCF concentrations were lower in patients with GISTs than in the controls (645 pg/mL vs 950 pg/mL, respectively; P Ͻ .0001; Table 1; Figure 1).…”

Section: Serum Kit Scf and Vegf Concentrations In Patients With Gissupporting

confidence: 69%

“…The ELISA protocol used to measure serum KIT (Nichirei Corporation, Tokyo, Japan) detects both normal and mutated serum KIT. 29 The assay uses mouse anti-human KIT Ab-coated microwells, and alkaline phosphatase-conjugated anti-KIT Ab as the secondary Ab. The results were read as AU/mL, where one unit equals to 1.4 ng/mL circulating KIT.…”

Section: Serum Concentrations Of Kit Scf and Vegfmentioning

confidence: 99%

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Serum KIT and KIT ligand levels in patients with gastrointestinal stromal tumors treated with imatinib

Bono

Krause

Mehren

et al. 2004

Blood

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Imatinib mesylate is a selective inhibitor of a few tyrosine kinases including KIT, and it is the first effective treatment for gastrointestinal stromal tumors (GISTs). We monitored the serum levels of KIT, KIT ligand (stem cell factor, SCF), and the vascular endothelial growth factor (VEGF) in patients with advanced GISTs treated with imatinib in a prospective randomized trial. Patients with GISTs (n ‫؍‬ 66) had elevated pretreatment serum KIT and VEGF levels as compared with controls (median, 292 AU/mL [409 ng/mL] vs 238 AU/mL [333 ng/mL], P ‫؍‬ .037; and median, 303 pg/mL vs 190 pg/mL, P ‫؍‬ .013, respectively), but lower levels of SCF (median, 645 pg/mL vs 950 pg/mL; P < .0001). After 1 and 6 months of imatinib treatment the average serum KIT levels decreased 31% and 52% from pretreatment levels, whereas SCF levels increased 11% and 33%, respectively. Serum VEGF levels decreased during treatment in responding patients. The median serum SCF/KIT ratio increased with treatment duration, and was 7.7-fold higher after 12 months of treatment than at baseline (range, 3.1-259-fold). A high serum SCF/KIT ratio may increase SCFinduced cell signaling with prolonged imatinib treatment, at the time when imatinib treatment is withdrawn, and in patients whose GIST has wild-type receptors.

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Section: Serum Kit Scf and Vegf Concentrations In Patients With Gissupporting

confidence: 69%

Section: Serum Concentrations Of Kit Scf and Vegfmentioning

confidence: 99%

Serum KIT and KIT ligand levels in patients with gastrointestinal stromal tumors treated with imatinib

Bono

Krause

Mehren

et al. 2004

Blood

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“…sKIT could also prolong the degradation of soluble SCF by forming a complex with sKIT (Broudy, 1997). Although the role that sKIT plays in vivo in modulating SCF function is still unclear, the serum sKIT concentration has been shown to be an indicator of the pathological state in various haematological disorders, such as AML, myeloid blastic crisis of CML (Kawakita et al, 1995) and SLE (Kitoh et al, 1998). In the present study sKIT levels in untreated CRF patients were significantly higher than those in healthy controls; however, those in HD-CRF patients were significantly lower than those in untreated CRF patients (Fig 1b).…”

Section: Discussionmentioning

confidence: 99%

“…Serum sKIT was measured by ELISA using two anti-human KIT mouse MoAb, L6 and L15 (Nichirei Corp., Tokyo, Japan), as described previously (Kawakita et al, 1995). The precision and accuracy of sKIT ELISA were reported previously (Kitoh et al, 1998).…”

Section: Methodsmentioning

confidence: 99%

“…Soluble SCF is released from these cells into the blood circulation (Langley et al, 1993). Soluble KIT (sKIT) is also found in blood Kawakita et al, 1995) and its main source is thought to be endothelial cells and haemopoietic cells (Broudy et al, 1994;Turner et al, 1995). In a previous study we determined the levels of SCF and sKIT in the serum of patients with systemic lupus erythematosus (SLE), and found that sKIT levels reflected the clinical status of SLE (Kitoh et al, 1998).…”

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Elevated SCF levels in the serum of patients with chronic renal failure

Kitoh¹,

Ishikawa²,

Ishii³

et al. 1998

Br J Haematol

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Summary. Serum stem cell factor (SCF) and soluble KIT (sKIT) levels were estimated in patients with chronic renal failure (CRF) and anaemia, and compared with clinical parameters of blood cells and renal function. Serum SCF levels in CRF patients were 5-fold higher than those in healthy controls. However, serum sKIT levels in haemodialysis (HD)-CRF patients were only slightly higher than those of healthy controls. In untreated CRF patients and healthy controls, serum SCF levels were significantly correlated with blood urea nitrogen (BUN), creatinine, haemoglobin, red blood cell (RBC) count and sKIT. In untreated CRF patients, serum SCF levels were significantly correlated with BUN, creatinine, and sKIT. These results suggest that serum SCF levels increased with the deterioration of renal function and might be related to erythropoiesis.

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Spermatogenesis in the golden hamster: The role of c‐kit

Vigodner

Lewin

Shochat

et al. 2001

Molecular Reproduction Devel

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c-kit is related to the family of transmembrane tyrosine kinase receptors. Mutations in genes for either c-kit or its ligand, Steel factor, result in infertility, but the role of c-kit/SCF system in spermatogenesis is not well understood. In this study Western blot analysis together with confocal microscopy were used to follow c-kit expression in hamsters during the first spermatogenic wave in mature animals and in old age. Three antibodies raised against different domains of c-kit were tested on Western Blot. Confocal microscopy was performed after incubation of fixed seminiferous tubules with tested antibodies followed by binding of FITC-labeled secondary antibody. Longitudinal sections of seminiferous tubule were observed by confocal microscopy to determine in which stages of spermatogenesis and in which cell types c-kit was found. C-kit bands of 80,140, and 150 kDa were observed on Western blot, indicating that c-kit is a name related to several proteins sharing some common domains. Only the band of 150 kDa correlated with positive staining of c-kit in tubules using confocal microscopy. We term this protein c-kit150T (150 kDa, testis). We demonstrated that c-kit150T appeared in differentiating hamster spermatogonia at stages VII-VIII of adult spermatogenesis and at day 13-14 during the first spermatogenic wave. It remained attached to the cell until late pachytene. This suggests that c-kit may play a role in preparing the germinal cells to enter meiosis. In order to evaluate the effect of aging on the number of germ cells, B2 spermatogonia/Sertoli cell ratio was calculated in the group of young animals (5-7 months) compared to this ratio in older ones (20-26 months). A significant decrease (P < 0.01) in the number of B2 spermatogonia in the group of old hamsters as compared to young ones was seen. The calculated value for the B2 spermatogonia/Sertoli cell ratio was 5.6 +/- 0.7 in young animals and 3.8 +/- 1.2 in the 20-26 months ones. In addition, decrease in the intensity of staining for c-kit was detected in the old hamsters. These may be the reasons for subfertility in old age and in other cases of testicular disorders.

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Soluble c‐kit molecule in serum from healthy individuals and patients with haemopoietic disorders

Cited by 27 publications

References 20 publications

Serum KIT and KIT ligand levels in patients with gastrointestinal stromal tumors treated with imatinib

Serum KIT and KIT ligand levels in patients with gastrointestinal stromal tumors treated with imatinib

Elevated SCF levels in the serum of patients with chronic renal failure

Spermatogenesis in the golden hamster: The role of c‐kit

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