Role of the hematopoietic cytokines SCF, IL-3, GM-CSF and M-CSF in the diagnosis of pancreatic and ampullary cancer

2012 ◽  
Vol 27 (3) ◽  
pp. 186-194 ◽  
Author(s):  
George Vasiliades ◽  
Nikolaos Kopanakis ◽  
Michalis Vasiloglou ◽  
George Zografos ◽  
Helias Margaris ◽  
...  

Background Previous studies have demonstrated altered levels of hematopoietic cytokines in the serum of patients with different types of cancer. Methods We measured the serum levels of the hematopoietic cytokines stem cell factor (SCF), interleukin 3 (IL-3), macrophage-colony stimulating factor (M-CSF) and granulocyte-macrophage-colony stimulating factor (GM-CSF) in 40 pancreatic and ampullary cancer patients and 40 healthy volunteers, using ELISA. We also assessed the most widely used pancreatic tumor markers, carbohydrate antigen 19–9 (CA 19–9) and carcinoembryonic antigen (CEA), in both groups. We then correlated the concentrations of the cytokines and the tumor markers in the patients’ serum and we estimated their diagnostic ability by calculating diagnostic sensitivity and specificity, positive and negative predictive values and the receiver operating characteristic (ROC) curve. Results The SCF and IL-3 levels were significantly lower and the M-CSF levels significantly higher in pancreatic cancer patients than in controls. There were significant positive correlations between the serum levels of CEA and M-CSF, GM-CSF and SCF, and between GM-CSF and IL-3. The area under the ROC curve and diagnostic sensitivity of M-CSF were greater than those of SCF and IL-3. The diagnostic sensitivity of the combined use of SCF and M-CSF reached 97.5%. Conclusion The diagnostic ability of M-CSF and SCF in pancreatic and ampullary cancer should stimulate further studies evaluating their clinical usefulness as tumor markers.

2018 ◽  
pp. 1-6
Author(s):  
Neemat M. Kassem ◽  
Alya M. Ayad ◽  
Noha M. El Husseiny ◽  
Doaa M. El-Demerdash ◽  
Hebatallah A. Kassem ◽  
...  

Purpose Granulocyte-macrophage colony-stimulating factor (GM-CSF) cytokine stimulates growth, differentiation, and function of myeloid progenitors. We aimed to study the role of GM-CSF gene expression, its protein, and antibodies in patients with acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) and their correlation to disease behavior and treatment outcome. The study included 50 Egyptian patients with AML/MDS in addition to 20 healthy volunteers as control subjects. Patients and Methods Assessment of GM-CSF gene expression was performed by quantitative real-time polymerase chain reaction. GM-CSF proteins and antibodies were assessed by enzyme-linked immunosorbent assay. Results There was significant decrease in GM-CSF gene expression ( P = .008), increase in serum level of GM-CSF protein ( P = .0001), and increase in anti–GM-CSF antibodies ( P = .001) in patients with AML/MDS compared with healthy control subjects. In addition, there was a significant negative correlation between serum levels of GM-CSF protein and initial peripheral blood blasts, percentage as well as response to therapy. Conclusion Any alteration in GM-CSF gene expression could have implications in leukemogenesis. In addition, GM-CSF protein serum levels could be used to predict outcome of therapy. GM-CSF antibodies may also play a role in the pathogenesis of AML/MDS. The use of these GM-CSF parameters for disease monitoring and as markers of disease activity needs further research.


2020 ◽  
Vol 15 (2) ◽  
pp. 131-136
Author(s):  
Diego Fiume ◽  
Ilaria Lenci ◽  
Martina Milana ◽  
Tommaso M. Manzia ◽  
Renato Massoud ◽  
...  

Background: Multiple biological functions have been recognized regarding Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) and Stem Cell Factor (SCF). Aim: 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. Methods: 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. Results: 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). Conclusions: During liver regeneration in humans, SCF serum levels are increased allowing to hypothesize a possible role of this chemokine during tissue growth and remodeling.


Author(s):  
Barbara Mroczko ◽  
Maciej Szmitkowski ◽  
Urszula Wereszczyńska-Siemiątkowska ◽  
Grażyna Jurkowska

AbstractHematopoietic cytokines (HCs) can affect the growth and spread of cancer. Therefore, in the present study, we investigated in pancreatic cancer patients the serum levels of selected HCs, such as stem cell factor (SCF), interleukin 3 (IL-3), granulocyte-macrophage-colony stimulating factor (GM-CSF), granulocyte-colony stimulating factor (G-CSF) and macrophage-colony stimulating factor (M-CSF) in relation to a control group and to a group of patients with chronic pancreatitis. Classical tumor markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) were also tested. We compared the serum level of cytokines with the tumor stage. The diagnostic sensitivity, specificity, positive and negative predictive values and receiver-operating characteristics (ROC) curve for cytokines and classical tumor markers were defined. The cytokines were measured in 48 patients with pancreatic cancer, in 23 patients with chronic pancreatitis and in 40 healthy subjects. HCs were determined using ELISA. CEA and CA 19-9 were measured by microparticle enzyme immunoassay. There were significant differences in the levels of circulating SCF, IL-3, GM-CSF, M-CSF, CEA and CA 19-9 in the pancreatic cancer patients compared to the control group. The serum levels of M-CSF and tumor markers were significantly higher in pancreatic cancer patients compared to the pancreatitis group. The levels of SCF, M-CSF and tumor markers were higher in patients with a more advanced tumor stage. The M-CSF serum levels in the pancreatitis group correlated positively with the tumor markers tested – CEA and CA 19-9. The diagnostic sensitivity of SCF and specificity of M-CSF and tumor markers were the highest. The SCF and M-CSF areas under the ROC curve were greater than the areas for other cytokines. These results suggest the potential usefulness of HCs in pancreatic cancer detection; however, further investigations of early-stage pancreatic cancer patients and confirmation by a prospective study are necessary.


Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 2960-2965 ◽  
Author(s):  
FM Rosenthal ◽  
R Fruh ◽  
R Henschler ◽  
H Veelken ◽  
P Kulmburg ◽  
...  

Development of cell-based delivery systems that can release therapeutic levels of hematopoietic growth factors into the systemic circulation would facilitate treatment of patients requiring cytokine therapy. In this study, we have investigated the potential of granulocyte- macrophage colony-stimulating factor (GM-CSF)-secreting, irradiated syngeneic murine cells to accelerate hematopoietic recovery after cytotoxic chemotherapy. As a model, CMS-5 fibrosarcoma cells, were transduced with a retroviral vector containing the murine GM-CSF cDNA. Transduced cells secreted 38 ng GM-CSF/10(6) cells in 24 hours. After irradiation, in vitro GM-CSF production initially increased up to fivefold and was measurable for about 2 weeks. One and 2 days after injection of irradiated, GM-CSF-secreting CMS-5 cells (N2/CMVGM- CSF/CMS5 # 6 cells) into mice, GM-CSF serum levels of 405 +/- 58 pg/mL and 183 +/- 36 pg/mL were measured, respectively. Serum levels were comparable with levels detected 3 hours after injection of 100 ng recombinant murine GM-CSF (rmGM-CSF) subcutaneously (90 pg/mL). Injection of N2/CMVGM-CSF/CMS5 # 6 cells in cyclophosphamide-treated mice was as effective in accelerating neutrophil recovery as twice daily subcutaneous injections of rmGM-CSF. These data suggest that irradiated hematopoietic growth factor-secreting cells might offer an alternative to parenteral injections of recombinant cytokines in the treatment of neutropenic patients.


Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 2960-2965 ◽  
Author(s):  
FM Rosenthal ◽  
R Fruh ◽  
R Henschler ◽  
H Veelken ◽  
P Kulmburg ◽  
...  

Abstract Development of cell-based delivery systems that can release therapeutic levels of hematopoietic growth factors into the systemic circulation would facilitate treatment of patients requiring cytokine therapy. In this study, we have investigated the potential of granulocyte- macrophage colony-stimulating factor (GM-CSF)-secreting, irradiated syngeneic murine cells to accelerate hematopoietic recovery after cytotoxic chemotherapy. As a model, CMS-5 fibrosarcoma cells, were transduced with a retroviral vector containing the murine GM-CSF cDNA. Transduced cells secreted 38 ng GM-CSF/10(6) cells in 24 hours. After irradiation, in vitro GM-CSF production initially increased up to fivefold and was measurable for about 2 weeks. One and 2 days after injection of irradiated, GM-CSF-secreting CMS-5 cells (N2/CMVGM- CSF/CMS5 # 6 cells) into mice, GM-CSF serum levels of 405 +/- 58 pg/mL and 183 +/- 36 pg/mL were measured, respectively. Serum levels were comparable with levels detected 3 hours after injection of 100 ng recombinant murine GM-CSF (rmGM-CSF) subcutaneously (90 pg/mL). Injection of N2/CMVGM-CSF/CMS5 # 6 cells in cyclophosphamide-treated mice was as effective in accelerating neutrophil recovery as twice daily subcutaneous injections of rmGM-CSF. These data suggest that irradiated hematopoietic growth factor-secreting cells might offer an alternative to parenteral injections of recombinant cytokines in the treatment of neutropenic patients.


Author(s):  
A. Riccio ◽  
M. De Caterina ◽  
D. Natale ◽  
E. Grimaldi ◽  
G. Pronesti ◽  
...  

In this report we investigate the behaviour of the serum levels of Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) in the course of Systemic Sclerosis (SS). This cytokine is produced mainly by T and NK cells, and its possible role in the pathogenesis of SS has not been previously described in the literature. Serum GM-CSF levels were assayed in 10 female patients, ageing from 35 to 70, affected by SS. These patients were not suffering from other disorders and were not being treated with steroids or immunosuppressive drug. A solid phase immunoenzymatic method was used to assess the serum levels of GM-CSF. Reference values were previously determined in a control group of 36 healthy women blood donors (19 premenopausal and 17 postmenopausal) (x̄=20.1 ±12.3 pg/ml). All the patients but one showed significantly increased serum levels of GM-CSF (x̄= 120.9 ±125.5 pg/ml). The highest levels were found in the two oldest patients, who also had the longest clinical history of SS, but a clear correlation with age, disease duration or clinical manifestations was not evident, even if the postmenopausal age group patients showed a higher mean value of GM-CSF (x̄= 148.0±144.1 pg/ml) than that found in the premenopausal age group (x̄= 57.7±1.4 pg/ml) (in contrast with the findings in the control group). The absence of other pathogenic conditions in our patients suggests that the increase in serum levels of GM-CSF might be linked to the fibroblast proliferation which is typical of SS. However, our results do not explain the role played by this factor in the fibroblastic proliferation process and an in vitro study is necessary to clarify this aspect.


Author(s):  
Barbara Mroczko ◽  
Maciej Szmitkowski ◽  
Urszula Wereszczynska-Siemiatkowska ◽  
Grazyna GrazynaJurkowska

AbstractStem cell factor (SCF)and macrophage-colony stimulating factor (M-CSF)have assumed an increasing importance in cancer biology. In the present study we investigated the serum levels of these cytokines in pancreatic cancer patients in relation to controls and to patients with benign lesions of the pancreas (chronic pancreatitis group). The classical tumor markers, such as carcinoembryonic antigen (CEA)and carbohydrate antigen 19–9 (CA 19–9)were also tested. We compared the serum levels of cytokines with tumor stage. We also defined the receiver-operating characteristics (ROC)curve for cytokines and classical tumor markers. The cytokines were measured in 47 patients with pancreatic cancer, in 27 patients with chronic pancreatitis and in 35 healthy subjects. SCF and M-CSF were determined using enzyme-linked immunosorbent assay (ELISA). CEA and CA 19–9 were measured by microparticle enzyme immunoassay. There were significant differences in the levels of circulating SCF, M-CSF, CEA and CA 19–9 in the pancreatic cancer patients compared to the control group, but only the serum levels of M-CSF, CEA and CA 19–9 were significantly higher in pancreatic cancer patients compared to the pancreatitis group. The levels of cytokines and tumor markers were higher in patients with a more advanced tumor stage. The M-CSF serum levels correlated positively with the tested tumor markers. The M-CSF area under the ROC curve was higher than the SCF area. These results suggest that M-CSF is a better candidate for a pancreatic cancer tumor marker than SCF.


Author(s):  
Barbara Mroczko ◽  
Maciej Szmitkowski

AbstractStem cell factor (SCF), interleukin 3 (IL-3), granulocyte-macrophage-colony stimulating factor (GM-CSF), granulocyte-colony stimulating factor (G-CSF) and macrophage-colony stimulating factor (M-CSF) are members of a group of glycoproteins called hematopoietic cytokines (HCs). These cytokines regulate the growth and differentiation of hematopoietic progenitor cells and functionally activate mature neutrophils or macrophages. The effect of HCs is not limited to bone marrow cells. Some studies have shown that HCs can also stimulate the proliferation of non-hematopoietic cells. The receptors for HCs have been detected in cancer cell lines, and stimulation of HCs receptors induced proliferation of tumor cells. Moreover, some investigations have shown HC mRNA expression in these cell lines and recent studies have demonstrated that HCs can stimulate tumor progression. Several cells of malignant tumors have been observed to secrete large amounts of HCs and increased concentrations of HCs have been found in the sera of cancer patients. There are a number of situations in which the measurement of HCs may provide clinically useful information, particularly regarding prognosis and response to treatment. In this paper we discuss the results of studies that have examined the potential use of HCs as tumor markers.


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