Serum Granulocyte Colony-stimulating Factor Levels Research Articles

The Potential Diagnostic Utility of SMAD4 and ACCS in the Context of Inflammation in Type 2 Diabetes Mellitus Patients.

The search for new parameters for the prediction of type 2 diabetes mellitus (T2DM) or its harmful consequences remains an important field of study. Depending on the low-grade inflammatory nature of diabetes, we investigated three proteins in T2DM patients: 1-aminocyclopropane-1-carboxylate synthase (ACCS), granulocyte-colony-stimulating factor (G-CSF), and Sma Mothers Against Decapentaplegic homolog-4 (SMAD4). In brief, sixty T2DM and thirty healthy controls had their serum levels of ACCS, G-CSF, SMAD4, and insulin tested using the ELISA method. The insulin resistance (IR) parameter (HOMA2IR), beta-cell function percentage (HOMA2%B), and insulin sensitivity (HOMA2%S) were all determined by the Homeostasis Model Assessment-2 (HOMA2) calculator. The predictability of these protein levels was investigated by neural network (NN) analysis and was associated with measures of IR. Based on the results, ACCS, G-CSF, and SMAD4 increased significantly in the T2DM group compared with the controls. Their levels depend on IR status and inflammation. The multivariate GLM indicated the independence of the levels of these proteins on the covariates or drugs taken. The receiver operating characteristic area under the curve (AUC) for the prediction of T2DM using NN analysis is 0.902, with a sensitivity of 71.4% and a specificity of 93.8%. The network predicts T2DM well with predicted pseudoprobabilities over 0.5. The model's predictive capability (normalized importance) revealed that ACCS is the best model (100%) for the prediction of T2DM, followed by G-CSF (75.5%) and SMAD4 (69.6%). It can be concluded that ACCS, G-CSF, and SMAD4 are important proteins in T2DM prediction, and their increase is associated with the presence of inflammation.

18F-FDG PET/CT Imaging of G-CSF-Producing Inflammatory Myofibroblastic Tumor of the Pleura.

We report a case of granulocyte colony-stimulating factor (G-CSF)-producing inflammatory myofibroblastic tumor of the pleura in a 71-year-old man. Contrast-enhanced CT demonstrated multiple pleural masses with pulmonary hilar lymph nodes swelling. 18F-FDG PET/CT demonstrated marked focal FDG uptake in the thoracic masses with diffuse uptake in the bone marrow. Based on the pathological findings and elevated serum G-CSF level, the patient was diagnosed as G-CSF-producing inflammatory myofibroblastic tumor. Because G-CSF-producing tumors demonstrate aggressive clinical course, early and accurate diagnosis is important.

Correlation between Serum G-CSF Level and Immune Function in Children with Aplastic Anemia

To observe the occurrence of immune dysfunction in children with aplastic anemia (AA) and the factors that may lead to immune dysfunction, analyze the relationship between the expression of granulocyte colony stimulating factor (G-CSF) and immune dysfunction. A total of 34 children with AA treated in our hospital from December 2016 to September 2018 were selected. All the children received immunosuppressive therapy (IST) for 6 months. According to whether the children had immune dysfunction after 6 months of treatment, they were divided into occurrence group and non occurrence group. General information and laboratory indices were compared between the two groups, and serum G-CSF level was tested, the relationship between serum G-CSF level and immune dysfunction in AA children after treatment with IST was observed and analyzed. After treatment with IST for 6 months, 12 cases developed immune dysfunction (35.29%). Serum interferon (IFN)-γ level of the occurrence group was higher but G-CSF level was lower than those of the non occurrence group (P<0.05), while the difference of other baseline data was not statistically significant (P>0.05). Multiple regression analysis showed that overexpression of serum IFN-γ and low expression of G-CSF were both the influencing factors of immune dysfunction in AA children after IST treatment (OR>1, P<0.05). ROC curve was drawn, and the result showed that the area under the curve (AUC) of serum G-CSF level predicted the risk of immune dysfunction after IST was 0.843>0.80, when the index cut-off value was set at 6.614 pg/ml, the predictive value was ideal. AA children have a higher risk of immune dysfunction after IST, which may be related to the low expression of serum G-CSF. The detection of serum G-CSF expression can be considered to predict the risk of immune dysfunction in AA children after IST, so as to guide early clinical intervention.

Profiling and multivariate analysis of serum cytokines in patients with generalized pustular psoriasis

Introduction: Generalized pustular psoriasis (GPP) is a chronic autoinflammatory disease characterized by fever, erythema, and sterile pustules occurring over large areas of the skin. The immunopathogenesis of GPP remains poorly understood. We aimed to profile serum cytokine levels in patients with GPP and analyze treatment-associated changes in cytokine levels. Methods: Twenty-four patients who were diagnosed with GPP and received drug treatment, together with 28 unaffected controls, were recruited in this study. Levels of 27 cytokines in serum samples from pre- and post-treated patients as well as unaffected controls were assessed using a Bio-Plex multiplex immunoassay. Multivariate analysis of cytokine levels and clinical parameters was conducted. Results: Serum levels of interleukins interleukin (IL)-1β, IL-1Ra, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, granulocyte colony-stimulating factor (G-CSF), interferon-γ (IFN-γ), IFN-γ-induced protein 10 (IP-10), monocyte chemoattractant protein-1, tumor necrosis factor-α, and vascular endothelial growth factor were significantly elevated (p &lt; .05) in patients with GPP compared with controls. Serum levels of IL-6, G-CSF, IL-8, IFN-γ, IL1-Ra, IL-10, IL-13, and IL-1β were correlated with GPP severity (r &gt; 0.4, p &lt; .001). Following treatment, serum levels of IL-6, IL-7, IL-12, IFN-γ, IL-1β, IL-4, IL-8, IL-10, IL-13, G-CSF, and IP-10 were significantly decreased (p &lt; .05) compared with pretreatment levels. Among these cytokines, levels of IL-6, IL-7, IL-8, IL-12, IL-13, and IP-10 were reduced to normal levels. Conclusion: GPP patients exhibited markedly elevated levels of cytokines and chemokines involved in both type 1 and type 2 immune responses, suggesting hypercytokinemia occurs in GPP patients. IL-6 showed the strongest correlation with GPP disease severity and other clinical parameters such as CRP level and fever, thus representing an index for GPP severity. Our data comprehensively documented the cytokine profiles of GPP patients and may provide insights into GPP pathogenesis.

Granulocyte colony-stimulating factor is not pathogenic in lupus nephritis.

Systemic lupus erythematosus (lupus) is an autoimmune disease characterized by autoantibodies that form immune complexes with self‐antigens, which deposit in various tissues, leading to inflammation and disease. The etiology of disease is complex and still not completely elucidated. Dysregulated inflammation is an important disease feature, and the mainstay of lupus treatment still utilizes nonspecific anti‐inflammatory drugs. Granulocyte colony‐stimulating factor (G‐CSF) is a growth, survival, and activation factor for neutrophils and a mobilizer of hematopoietic stem cells, both of which underlie inflammatory responses in lupus. To determine whether G‐CSF has a causal role in lupus, we genetically deleted G‐CSF from Lyn‐deficient mice, an experimental model of lupus nephritis. Lyn−/−G‐CSF−/− mice displayed many of the inflammatory features of Lyn‐deficient mice; however, they had reduced bone marrow and tissue neutrophils, consistent with G‐CSF's role in neutrophil development. Unexpectedly, in comparison to aged Lyn‐deficient mice, matched Lyn−/−G‐CSF− /− mice maintained neutrophil hyperactivation and exhibited exacerbated numbers of effector memory T cells, augmented autoantibody titers, and worsened lupus nephritis. In humans, serum G‐CSF levels were not elevated in patients with lupus or with active renal disease. Thus, these studies suggest that G‐CSF is not pathogenic in lupus, and therefore G‐CSF blockade is an unsuitable therapeutic avenue.

Histidine decarboxylase deficiency inhibits NBP-induced extramedullary hematopoiesis by modifying bone marrow and spleen microenvironments.

Histidine decarboxylase (HDC), a histamine synthase, is expressed in various hematopoietic cells and is induced by hematopoietic cytokines such as granulocyte colony-stimulating factor (G-CSF). We previously showed that nitrogen-containing bisphosphonate (NBP)-treatment induces extramedullary hematopoiesis via G-CSF stimulation. However, the function of HDC in NBP-induced medullary and extramedullary hematopoiesis remains unclear. Here, we investigated changes in hematopoiesis in wild-type and HDC-deficient (HDC-KO) mice. NBP treatment did not induce anemia in wild-type or HDC-KO mice, but did produce a gradual increase in serum G-CSF levels in wild-type mice. NBP treatment also enhanced Hdc mRNA expression and erythropoiesis in the spleen and reduced erythropoiesis in bone marrow and the number of vascular adhesion molecule 1 (VCAM-1)-positive macrophages in wild-type mice, as well as increased the levels of hematopoietic progenitor cells and proliferating cells in the spleen and enhanced expression of bone morphogenetic protein 4 (Bmp4), CXC chemokine ligand 12 (Cxcl12), and hypoxia inducible factor 1 (Hif1) in the spleen. However, such changes were not observed in HDC-KO mice. These results suggest that histamine may affect hematopoietic microenvironments of the bone marrow and spleen by changing hematopoiesis-related factors in NBP-induced extramedullary hematopoiesis.

Different changes in granulocyte-colony stimulating factor and its correlation with inflammatory biomarkers in patients after traumatic brain injury.

This study analyzed changes in granulocyte-colony stimulating factor (G-CSF) and its correlation with leukocyte and neutrophil counts in patients after traumatic brain injury (TBI). Sixty TBI patients were included retrospectively. The serum levels of G-CSF, tumor necrosis factor-α (TNF-α), and peripheral leukocyte and neutrophil counts at different time points were measured and analyzed, and the 6-month functional outcomes were monitored. The levels of G-CSF in mild and moderate TBI groups were higher than the control at the first three time points. G-CSF in the severe TBI group increased slowly and peaked at day 7, and was only significantly different from the control at day 7 and 14. The leukocyte and neutrophil counts of the mild group gradually decreased, but a second increase after day 4 was observed in the severe group. The cell counts were higher in the severe group compared to other groups. A positive correlation between G-CSF and leukocyte and neutrophil counts was observed in the severe group at day 1. G-CSF positively correlated with TNF-α in the severe group at day 4 and 7. In severe patients with a good outcome, G-CSF level at day 7 was significantly higher than those with a poor outcome. The G-CSF levels in the severe TBI group exhibited a different pattern from those in the mild and moderate TBI groups, and these levels positively correlated with inflammatory biomarkers. Higher G-CSF levels in severe TBI at day 7 indicated a good outcome at 6 months.

Serum cytokine, chemokine, and growth factor profiles and their modulation in inflammatory bowel disease

Ulcerative colitis (UC) and Crohn disease (CD) are the most common forms of inflammatory bowel disease (IBD). Because these subtypes of IBD are characterized by periods of activity and remission, an understanding of the modulation of biochemical markers with the clinical features of IBD or its treatment, may be useful for determining the correct treatment protocol.This study aimed to evaluate the serum levels of 27 protein biomarkers to determine their association with IBD, correlation with clinical findings of disease, and modulation according to the pharmacologic therapy.A case–control study was carried out in Zacatecas, Mexico. The 27 protein profiles of serum from 53 participants (23 UC, 11 CD, and 19 controls) were evaluated using the Pro Human Cytokine 27-Plex immunoassay (Bio-Rad).Considering the controls as a reference, the group with IBD endoscopic activity showed higher serum levels of granulocyte colony-stimulating factor (G-CSF), interleukin 1 receptor antagonist (IL-1Ra), and platelet-derived growth factor BB (PDGF-BB) (P < .05). Interferon-induced protein 10 (IP-10) was associated with extraintestinal symptoms of disease (P = .041). Both PDGF-BB and interleukin 6 (IL-6) showed the strongest correlations with clinical features of IBD. Levels of IL-6, IL-7, and monocyte chemoattractant protein 1 were higher with 5-aminosalicylic acid (5-ASA) + Azathioprine therapy than controls (P < .05). Combined therapy with 5-ASA + Adalimumab led to the strongest changes in marker modulation: IL-4, IL-5, IL-15, and PDGF-BB, were upregulated (P < .05).Elevated serum levels of G-CSF, IL-1Ra, and PDGF-BB were associated with IBD endoscopic activity, and of IP-10 with extraintestinal manifestations of IBD. Combined therapy of 5-ASA + Adalimumab produced significant upregulation of IL-4, IL-5, IL-15, and PDGF-BB. This information may be useful for deciding on the course of pharmacologic therapy for patients with IBD and for generating new therapy alternatives to improve the outcome of patients with IBD.

Leukocytosis Associated with Esophageal Squamous Cell Carcinoma as a Predictor of Poor Prognosis - A Case Report and Review of Literature

Leukocytosis, specifically granulocytosis in malignancy is a common finding with various etiologies. Graulocytosis associated with esophageal cancer has not commonly been reported in case reports in the United States. Furthermore, granulocyte colony stimulating factor (G-CSF) producing tumors have been associated with a variety of cancers. However, G-CSF producing esophageal tumors are rare. The diagnosis is established through serum G-CSF levels and immunohistochemistry staining of tumor cells. Here, we report a case of a 72-year-old woman with persistent granulocytosis leading to the diagnosis of esophageal squamous cell carcinoma (ESCC). Although, our case did not report serum G-CSF levels, we strongly suspect it to be the underlying etiology in our case. Additionally, through our missed opportunity, we hope to emphasize and increase awareness of G-CSF producing ESCC.

Development of membranoproliferative glomerulonephritis-like glomerulopathy in a patient with neutrophilia resulting from endogenous granulocyte-colony stimulating factor overproduction: a case report

BackgroundThe pathophysiologic role of exogenous granulocyte-colony stimulating factor (G-CSF) administration is reportedly linked to the progression of glomerulonephritis. However, the relationship between endogenous G-CSF overproduction and the progression of glomerulopathy has not been well investigated.Case presentationA 76-year-old woman presented with neutrophilia at a medical check-up and thorough examination revealed a high level of serum G-CSF. She subsequently developed mild renal dysfunction and proteinuria. Her renal biopsy showed lobulation of the glomeruli with mesangial proliferation and glomerular capillary walls with a double contour but no immune complex deposition, suggesting membranoproliferative glomerulonephritis-like glomerulopathy. Thereafter, her proteinuria levels fluctuated in parallel with the changes in her blood neutrophil count and finally reduced considerably in association with her decreased neutrophil count.ConclusionsThe unique features of this case suggest that endogenous overproduction of G-CSF could play an important role in the pathogenesis of active glomerulonephritis.

Hepatocellular carcinoma producing granulocyte colony-stimulating factor: diagnosis and treatment

Granulocyte colony-stimulating factor (G-CSF) is a naturally occurring glycoprotein that is synthesized by stromal cells in bone marrow. Several cases of G-CSF-producing malignant tumors in various organs have been reported, but it is extremely rare in hepatocellular carcinoma (HCC). Here, we report a rare case of HCC producing G-CSF. The patient presented with a continuous fever and had a huge liver mass in the right lobe with portal vein tumor thrombus (PVTT) in the right first branch. He had marked granulocytosis, and his serum level of G-CSF was elevated. A complete curative liver resection was performed after preoperative radiotherapy to PVTT. The pathological findings of the resected specimen revealed poorly/moderately differentiated HCC, and immunohistochemical staining of G-CSF was negative the first time it was tested, but the second time, it was positive in the cytoplasm of other tumor cells of HCC. Only a few cases of G-CSF-producing HCC have been reported, and they resulted in rapid tumor growth, metastases, and poor prognosis. In our case with PVTT, there was no liver recurrence, although multiple lung metastases occurred at 8months after curative resection. We should consider G-CSF-producing HCC and diagnose promptly when encountering liver tumor patients with leukocytosis, and we should perform multimodal treatment including radiation, radical surgery, and chemotherapy.

The dark side of granulocyte-colony stimulating factor: a supportive therapy with potential to promote tumour progression.

Granulocyte-colony stimulating factor (G-CSF) is one of several cytokines that can expand and mobilize haematopoietic precursor cells from bone marrow. In particular, G-CSF mobilizes neutrophils when the host is challenged by infection or tissue damage. Severe neutropenia, or febrile neutropenia is a life-threatening event that can be mitigated by administration of G-CSF. Consequently, G-CSF has been used to support patients undergoing chemotherapy who would otherwise require dose reduction due to neutropenia. Over the past 10-15years it has become increasingly apparent, in preclinical tumour growth and metastasis models, that G-CSF can support tumour progression by mobilization of tumour-associated neutrophils which consequently promote tumour dissemination and metastasis. With the increasing use of G-CSF in the clinic, it is pertinent to ask if there is any evidence of a similar promotion of tumour progression in patients. Here, we have reviewed the preclinical and clinical data on the potential contribution of G-CSF to tumour progression. We conclude that, whilst the evidence for a promotion of metastasis is strong in preclinical models and that limited data indicate that high serum G-CSF levels in patients are associated with poorer prognosis, no studies published so far have revealed evidence of increased tumour progression associated with supportive G-CSF use during chemotherapy in patients. Analysis of G-CSF receptor positive cohorts within supportive trials, as well as studies of the role of G-CSF blockade in appropriate tumours in the absence of chemotherapy could yield clinically translatable findings.

Dynamic changes in growth factor levels over a 7-day period predict the functional outcomes of traumatic brain injury.

Traumatic brain injury (TBI) can result in poor functional outcomes and death, and overall outcomes are varied. Growth factors, such as angiopoietin-1 (Ang-1), vascular endothelial growth factor (VEGF), and granulocyte-colony stimulating factor (G-CSF), play important roles in the neurological functions. This study investigated the relationship between serum growth factor levels and long-term outcomes after TBI. Blood samples from 55 patients were collected at 1, 3 and 7 days after TBI. Blood samples from 39 healthy controls were collected as a control group. Serum Ang-1, G-CSF, and VEGF levels were measured using ELISA. Patients were monitored for 3 months using the Glasgow Outcome Scale-Extended (GOSE). Patients having a GOSE score of > 5 at 3 months were categorized as a good outcome, and patients with a GOSE score of 1-5 were categorized as a bad outcome. Our data demonstrated that TBI patients showed significantly increased growth factor levels within 7 days compared with healthy controls. Serum levels of Ang-1 at 1 and 7 days and G-CSF levels at 7 days were significantly higher in patients with good outcomes than in patients with poor outcomes. VEGF levels at 7 days were remarkably higher in patients with poor outcomes than in patients with good outcomes. Receiver operating characteristic analysis showed that the best cut-off points of serum growth factor levels at 7 days to predict functional outcome were 1,333 pg/mL for VEGF, 447.2 pg/mL for G-CSF, and 90.6 ng/mL for Ang-1. These data suggest that patients with elevated levels of serum Ang-1, G-CSF, and decreased VEGF levels had a better prognosis in the acute phase of TBI (within 7 days). This study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1800018251) on September 7, 2018.

Systemic chemotherapy with pronounced efficacy and neutropenia in a granulocyte-colony stimulating factor-producing advanced gastric neuroendocrine carcinoma.

An advanced granulocyte-colony stimulating factor (G-CSF)-producing tumor is rare, and it exhibits leukocytosis in association with high serum G-CSF levels. A 67-year-old male with a 1-month history of bloody emesis and black stools was revealed to exhibit leukocytosis, anemia and a high serum concentration of G-CSF. During a gastrointestinal endoscopy, an ulcerating tumor was identified in the stomach. Computed tomography and a fluorodeoxyglucose-positron emission tomography scan demonstrated direct invasion of the gastric tumor into the transverse colon, regional lymphadenopathy, lung nodules and diffuse high uptake of FDG in bone marrow. The histological diagnosis was a G-CSF-producing neuroendocrine carcinoma (NEC) (tumor 4b, node 2, metastasis 1, pulmonary, clinical stage IV). Systemic chemotherapy consisting of cisplatin and irinotecan was started. Common terminology criteria of adverse events grade 3 tumor lysis syndrome and gastric penetration appeared. Grade 4 neutropenia lasted for 10 days despite intensive G-CSF administration. Prominent shrinkage of the primary and the metastatic tumors was observed subsequent to 3 cycles of chemotherapy. Total gastrectomy and resection of the transverse colon were subsequently performed. Systemic chemotherapy was effective for a G-CSF-producing advanced gastric NEC with careful monitoring and appropriate supportive care for severe adverse events.

Inhaled corticosteroids increase blood neutrophil count by decreasing the expression of neutrophil adhesion molecules Mac-1 and L-selectin

ObjectiveThe objective was to investigate the effect of commonly used inhaled corticosteroids on white blood cell count (WBC) and to examine the mechanisms involved. MethodsThis randomized comparative study comprised 60 healthy adults. We measured the effects of budesonide (by face mask inhalation or aerosol inhaler), fluticasone (by inhaler), and saline inhalation (control) on WBC and the differential leukocyte count, especially the absolute neutrophil count (ANC). To elucidate the mechanisms involved, we measured the expression of the adhesion neutrophil ligands Mac-1 (CD11b) and L-selectin (CD62L), and granulocyte colony-stimulating factor serum levels. ResultsSix hours after a single-dose inhalation of budesonide, mean increases of 23.4% in WBC (95% confidence interval [CI], 11.3-35.4) and 30.1% in ANC (95% CI, 7.2-53.0) were noted. The percentage of neutrophils increased from 54.6% to 58.1% (P< .001). Inhaled fluticasone increased WBC and ANC by 12.6% (95% CI, 1.5-23.7) and 22.7% (95% CI, 6.2-39.2), respectively (P< .01 for both). The absolute lymphocyte and eosinophil counts did not change significantly from baseline.The expression of Mac-1 and L-selectin decreased by 51.0% (P< .01) and 30.9% (P= .02), respectively, following face mask inhalation of budesonide and by 39.8% (P= .01) and 17.4% (P= .17), respectively, following inhalation of fluticasone. No significant changes in granulocyte colony-stimulating factor levels were noted. ConclusionsGlucocorticoid inhalation increases WBC by increasing ANC. Reduced neutrophil adhesion to the endothelial surface, mediated by decreased adhesion molecule expression on neutrophils, is a plausible mechanism. Physicians should be aware of the effect of inhaled corticosteroids on WBC, as it may influence clinical decisions, especially in the emergency department.

Atrial natriuretic peptide protects against cisplatin-induced granulocytopenia.

Granulocytopenia is the major toxicity associated with cisplatin treatment. Atrial natriuretic peptide (ANP) is a cardiac hormone used clinically for the treatment of acute heart failure in Japan. ANP exerts a wide range of protective effects on various organs, including the heart, blood vessels, lungs, and kidneys. This study's objective was to investigate the protective effects of ANP on cisplatin-induced granulocytopenia in mice. The mice were divided into two groups: cisplatin with vehicle and cisplatin with ANP. ANP (1.5μg/kg/min via osmotic pump, subcutaneously) or vehicle administration was started 1day before cisplatin injection until the mice were killed. At 0, 2, 4, 8, and 14days after cisplatin injection (16mg/kg, intraperitoneally as a single dose), the white blood cell, red blood cell, and platelet counts were measured in the peripheral blood in both groups. The numbers of total and live cells and colony-forming unit-granulocyte-macrophage (CFU-GM) colonies in the bone marrow of the mice were also examined. In addition, at 0, 0.5, 1, and 2days after cisplatin injection, serum granulocyte colony-stimulating factor (G-CSF) levels were measured. ANP significantly attenuated the white blood cell count decrease in the peripheral blood 2 and 4days after cisplatin injection. ANP also attenuated the decrease in the number of live cells and CFU-GM colonies in bone marrow 2, 4, and 8days after cisplatin injection. ANP significantly increased serum G-CSF levels 1day after cisplatin injection. ANP has protective effects in cisplatin-induced granulocytopenia, with increased G-CSF production.

Abstract P4-04-22: Upregulation of the interleukin 17/granulocyte-colony stimulating factor/fibroblast growth factor axis in breast cancer and its negative association with treatment outcome

Abstract Background Interleukin (IL) 17 is secreted by T helper 17 cells and tumor cells. It may induce the proliferation of mesenchymal stem cells (MSCs) in the tumor microenvironment directly and/or via fibroblast growth factor (FGF) and granulocyte-colony stimulating factor (G-CSF) production by tumor-associated macrophages. MSCs play various roles in tumor development and progression, by mediating tumor cell migration, promoting angiogenesis, regulating immune responses, and inducing anti-cancer drug resistance. Therefore, in this study, we examined the association of the IL17/FGF/G-CSF axis with both breast cancer development and response to chemotherapy. Methods Eighty-nine breast cancer patients (34% with luminal, 45% with HER2, and 21% with triple-negative breast cancer) and 55 healthy volunteers were analyzed. Serum IL17, basic FGF, and G-CSF levels were measured using a Luminex system. The primary objective was to evaluate the difference in IL17 serum levels between breast cancer patients and healthy volunteers. Secondary objectives were to determine the correlation of IL17 levels with the basic FGF and G-CSF levels, pathological complete response (pCR) (if neoadjuvant therapy was administered), and disease-free survival (DFS) in breast cancer patients. Statistical analyses were performed using the Mann-Whitney, chi-squared, and log-rank tests. Results Serum levels of IL17 (median, 91.9 vs. 40.3 pg/ml, p&amp;lt;0.0001), basic FGF (median, 63.9 vs. 3.15 pg/ml, p&amp;lt;0.0001), and G-CSF (median, 61.0 vs. 29.4 pg/ml, p&amp;lt;0.0001) were significantly higher in breast cancer patients than in healthy volunteers. IL17 levels were strongly correlated with basic FGF (r=0.86, p&amp;lt;0.0001) and G-CSF (r=0.73, p&amp;lt;0.0001) levels. Among 64 patients who received neoadjuvant therapy, those with low IL17 levels (&amp;lt;91.9 pg/ml) achieved a significantly higher pCR rate than those with high IL17 levels (≥91.9 pg/ml) (56.0% vs. 25.6%, p=0.014). In addition, the DFS at a median follow-up of 35.7 months was significantly higher in patients with low IL17 levels (p=0.0190). Conclusion The IL17/FGF/G-CSF axis was upregulated in breast cancer patients and the levels of these markers were inversely correlated with pCR and prognosis. These results may provide novel insight into the role of IL17 in tumor development and have important implications in the development of IL17 as a target in the treatment of breast tumors. Citation Format: Kawaguchi K, Suzuki E, Yamamoto Y, Saito K, Toi M. Upregulation of the interleukin 17/granulocyte-colony stimulating factor/fibroblast growth factor axis in breast cancer and its negative association with treatment outcome. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-04-22.

Gastric metastasis from esophageal squamous cell carcinoma producing granulocyte colony-stimulating factor: report of a case and literature review

We report an extremely rare case of gastric metastasis from a granulocyte colony-stimulating factor (G-CSF)-producing carcinoma of the esophagus. A 63-year-old Japanese man presented with an aggressive esophageal and gastric tumor and concomitant severe leukocytosis (21,700/mm3) with pyrexia. The serum level of G-CSF was markedly elevated to 253 pg/ml (normal < 9.8 pg/ml). Histological examination of the surgical specimen showed a moderately differentiated squamous cell carcinoma (SCC) of the esophagus and stomach, with tumor cells immunohistochemically positive for G-CSF. The leukocyte count and G-CSF concentration decreased after surgery. The patient was diagnosed with G-CSF-producing esophageal SCC with gastric metastasis. This is the first case of G-CSF-producing esophageal SCC with gastric metastasis.

Comparison of serum granulocyte colony-stimulating factor levels between preterm and term births.

Preterm birth (PTB) is the major obstetric problem in developed countries, accounting for the majority of neonatal mortality and morbidity. Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic cytokine that mediates the increase in leukocytes in pregnancy and may play a role in placentation. We aimed to investigate the differences of serum G-CSF levels between subsequent spontaneous PTB and term-delivered healthy pregnant women. Serum samples, collected from total of 600 singleton otherwise healthy pregnants at 24-28 weeks of gestation during a routine antenatal visit, were used to assess G-CSF levels; 40 of the total pregnants who delivered their infants spontaneously after preterm labor before 37 weeks of gestation were selected as the study group. Also, 120 pregnants were selected as a control group using a 1/3 ratio. Student's t-test, chi-square test, Mann-Whitney U-tests, and ROC curve analysis for prediction of PTB were used for the comparison of groups. P<0.05 was accepted as statistically significant. There was no significant difference in maternal serum G-CSF levels between the study and control groups (p=0.28) but maternal white blood cell (WBC) count was significantly different between them (p=0.00). In addition, G-CSF was insufficient in the prediction of PTB (AUC=0.419). In the preterm and term groups, no correlation was found between WBC and G-CSF (p=0.165 vs. p=0.703). There were no differences in serum levels of G-CSF between term- and preterm-delivered pregnants. There was no predictive role for serum G-CSF in PTB.

Abstract 1103: MDSC targeting therapy for uterine cervical cancer displaying TRL

Abstract Objectives: The aim of this study was to investigate the clinical implications and underlying mechanism of tumor-related-leukocytosis (TRL) in cervical cancer. Methods: The clinical data of cervical cancer patients who were treated with definitive radiotherapy were analyzed to investigate the association between TRL and treatment outcome in retrospective and prospective settings. Clinical samples, cervical cancer cell lines, and a mouse model of cervical cancer were employed to examine the mechanisms responsible for TRL in cervical cancer, focusing on the myeloid-derived suppressor cell (MDSC) and tumor-derived granulocyte colony-stimulating factor(G-CSF). Results: TRL was significantly associated with shorter survival. The TRL-positive patients displayed upregulated tumor G-CSF expression and elevated serum G-CSF levels and increased MDSC frequencies in the blood compared with the TRL-negative patients. In vitro and in vivo investigations revealed that tumor-derived G-CSF is involved in the underlying causative mechanism of TRL and that the increase in the number of MDSC induced by tumor-derived G-CSF is responsible for the rapidly progressive nature of TRL-positive cervical cancer. The administration of anti-Gr-1 antibody or the depletion of MDSC by splenectomy significantly inhibited tumor growth in TRL-positive cervical cancer. Conclusion: TRL is an indicator of a poor prognosis in cervical cancer patients treated with definitive radiotherapy. MDSC induced by tumor-derived G-CSF is responsible for the rapidly progressive nature of TRL-positive cervical cancer. MDSC-targeting treatments might have therapeutic potential in TRL-positive cervical cancer. Note: This abstract was not presented at the meeting. Citation Format: Yuri Matsumoto, Mahiru Kawano, Tomoyuki Sasano, Seiji Mabuchi. MDSC targeting therapy for uterine cervical cancer displaying TRL. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1103. doi:10.1158/1538-7445.AM2014-1103