Serum Granulocyte Colony-stimulating Factor Research Articles

G-CSF producing pleomorphic carcinoma with undetected origin: an autopsy case report

Pleomorphic carcinoma is an uncommon neoplasm that is known to arise in diverse sites, including the lung, breast, pancreas, gallbladder and prostate. We encountered a rare case of pleomorphic carcinoma of undetected origin associated with production of granulocyte-colony stimulating factor (G-CSF). The patient was a 62-year-old man who presented with cough and general fatigue. Chest computed tomography (CT) demonstrated a mass lesion in the mediastinum, so mediastinoscopic tumor biopsy was performed. However, making the diagnosis was difficult despite the suspected malignant potential. CT-supported positron emission tomography showed multiple uptake lesions in the small intestine, duodenum and right adrenal gland, in addition to the mediastinum. The patient subsequently presented with right-side weakness and sensory impairment. Brain CT showed multiple intracerebral lesions, indicating metastatic tumors. For the definitive diagnosis and to clarify options for chemotherapeutic management, the patient underwent surgical craniotomy. The resected specimen was considered to represent sarcomatoid carcinoma with positive immunoreactive staining for cytokeratin as an epithelial marker, indicating pleomorphic carcinoma. Furthermore, laboratory data showed leukocytosis without any infections and elevated serum G-CSF levels during hospitalization. The patient developed complications of occlusive intussusception in the small intestine caused by probably metastatic lesions and died from disease progression 82 days after initial admission. Although the presence of G-CSF-producing pleomorphic carcinoma was confirmed, the primary origin of this pleomorphic carcinoma could not be indentified clearly even at autopsy.

Balugrastim: A long-acting, once-per-cycle, recombinant human albumin-fusion filgrastim.

e13551 Background: Balugrastim is a once-per-cycle fixed-dose genetic fusion protein composed of human serum albumin (HSA) and granulocyte colony-stimulating factor (G-CSF) in development for prevention of severe neutropenia in cancer patients receiving chemotherapy. Albumin fusion is a clinically validated technology that extends product half-life, allowing for infrequent dosing, better tolerability, lower cost, and improves drug design, potentially lowering immunogenicity risk. Here, we describe the technology used to produce balugrastim and summarize preclinical findings compared with pegfilgrastim (Neulasta). Methods: Design and production of balugrastim was described previously (Halpern et al. Pharmaceut Res 2002;19:1720−1729). Biologic activity of balugrastim was assessed in an NFS-60 cell line proliferation assay vs filgrastim and pegfilgrastim. PK and PD properties were studied in healthy and neutropenic animal models. Results: Albumin fusion produces a long-acting G-CSF with comparable pharmacologic properties to pegfilgrastim. In vitro, balugrastim had binding affinity and cell proliferation activity comparable to pegfilgrastim, and both were lower than non-PEGylated filgrastim on a molar basis. Overall increases in leukocytes, neutrophilic granulocytes, and monocytes were dose dependent and consistent with the effects expected for a long-acting G-CSF with some variation based on the specific animal model used. A single balugrastim dose in BDF1 mice elicited a dose-dependent increase in peripheral granulocytes and mobilized hematopoietic progenitor cells. In cynomolgus monkeys, balugrastim caused an increase in peripheral neutrophils similar to pegfilgrastim, with higher responses after 2nd, 3rd, and 4th doses. In mice, balugrastim had shorter terminal half-life and mean residence time, and faster clearance than pegfilgrastim. In monkeys, terminal half-life of balugrastim was slightly longer than pegfilgrastim. Conclusions: An albumin fusion technology platform was used to produce balugrastim – a novel, biologically active albumin G-CSF fusion protein with greater structural homogeneity and comparable pharmacologic properties to conventionally PEGylated G-CSFs.

Pancreatitis activates pancreatic apelin-APJ axis in mice

Pancreatitis is classified into acute pancreatitis (AP) and chronic pancreatitis (CP). Apelin, a small regulatory peptide, is the endogenous ligand for the APJ receptor. Apelin and APJ are expressed in the pancreas. The aims of this study were to examine whether apelin influences the inflammatory and fibrosis responses to pancreatitis in mice and to identify mechanisms behind apelin's activities. Supramaximal cerulein induction of AP or CP caused significant (P < 0.05) elevations in pancreatic apelin and APJ expression. Levels declined during the recovery phases. In apelin gene-knockout mice with pancreatitis, pancreatic neutrophil invasion and myeloperoxidase activity were enhanced significantly, and apelin treatment suppressed both. Apelin exposure reduced CP-induced elevations of extracellular matrix-associated proteins. Apelin inhibited PDGF-simulated connective tissue growth factor production and proliferation of pancreatic stellate cells (PSCs). Serum granulocyte colony-stimulating factor and keratinocyte cytokine levels were higher in apelin gene-knockout than wild-type mice with pancreatitis. Apelin reduced AP- and CP-induced elevations in pancreatic NF-κB activation. Together, these findings imply that the pancreatic apelin-APJ system functions to curb the inflammatory and fibrosis responses during pancreatitis. Furthermore, findings suggest that apelin reduces inflammation and fibrosis by reducing neutrophil recruitment and PSC activity. Inhibition of neutrophil invasion may be mediated by reduced keratinocyte cytokine and granulocyte colony-stimulating factor secretion. Apelin-induced reductions in PSC proliferation and connective tissue growth factor production are putative mechanisms underlying apelin's inhibition of extracellular matrix production. The apelin-associated changes in NF-κB binding may be linked to apelin's regulation of pancreatic inflammatory and fibrosis responses during pancreatitis.

Granulocyte‐colony stimulating factor‐producing cervical cancers treated with carbon‐ion irradiation

Granulocyte-colony stimulating factor (G-CSF)-producing tumor is a rare condition. It has an aggressive nature and shows resistance to conventional treatments. We report two cases of G-CSF-producing uterine cervical cancer who were successfully treated with carbon-ion radiotherapy (C-ion RT). The first case was a 76-year-old woman with stage IIIB uterine cervical cancer, and the second was a 75-year-old woman with bulky stage IIB disease. Prior to treatment, both patients presented severe granulocytosis and elevated serum G-CSF concentrations. After C-ion RT, their cervical tumors completely disappeared, and their granulocytosis and elevated serum G-CSF levels improved as well. C-ion RT has been reported to be effective for various aggressive tumors, and it may be a good treatment option for this rare aggressive tumor.

Increased Circulation of Galectin-3 in Cancer Induces Secretion of Metastasis-Promoting Cytokines from Blood Vascular Endothelium

Cytokines such as interleukin (IL)-6 and granulocyte colony-stimulating factor (G-CSF) are important metastasis promoters. This study has investigated the functional significance of the increased circulation of galectin-3, a common feature in patients with cancer and in particular those with metastasis, on cytokine secretion from the blood vascular endothelium in cancer. The effects of galectin-3 on secretion of cytokines from human microvascular lung endothelial cells were assessed in vitro by cytokine array and in vivo in mice. The consequences of galectin-3-induced cytokine secretion on endothelial cell behaviors were determined, and the relationship between the levels of circulating galectin-3 and cytokines in patients with colorectal cancer with and without metastasis was investigated. Galectin-3 at pathologic concentrations found in patients with cancer induces secretion of IL-6, G-CSF, sICAM-1, and granulocyte macrophage colony-stimulating factor from blood vascular endothelial cells in vitro and in mice. These cytokines autocrinely/paracrinely interact with the vascular endothelium to increase the expressions of endothelial cell surface adhesion molecules integrinα(v)β(1), E-selectin, ICAM-1, and VCAM-1, resulting in increased cancer cell-endothelial adhesion and increased endothelial cell migration and tubule formation. In patients with metastatic colon cancer, higher serum galectin-3 levels correlated significantly with increased serum G-CSF, IL-6, and sICAM1 concentrations. The increased circulation of galectin-3 in patients with cancer induces secretion of several metastasis-promoting cytokines from the blood vascular endothelium that enhances endothelial cell activities in metastasis. Targeting the actions of circulating galectin-3 in patients with cancer therefore represents a promising therapeutic strategy to reduce metastasis and improve survival.

The role of pro-inflammatory cytokines and immune cells in colorectal carcinoma progression

Cytokines exhibit a pleiotropic effect in the regulation of the immune cell function, tumor growth and antitumor immune responses. A total of 30 patients with colorectal carcinoma were enrolled on this study and their levels of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, serum granulocyte colony-stimulating factor (sG-CSF) and serum macrophage colony-stimulating factor (sM-CSF) were measured preoperatively using ELISA. Tumor-infiltrating granulocyte (TIG), tumor-associated macrophage (TAM), G-CSF and M-CSF expression in tumor cells were examined using immunostaining. This study revealed abnormal levels of cytokines in patients, including IL-1β (1/30, 3.3%), IL-6 (16/30 53.3%), IL-81 (15/30, 50%), TNF-α (4/21, 19%), sG-CSF (17/30, 56.7%) and sM-CSF (4/21, 19%). There was a positive linear correlation between IL-6 and sM-CSF (P=0.017, R=0.517). sG-CSF was significantly associated with a deeper tumor invasion (P=0.039) and a more advanced tumor stage (P=0.023). The granulocyte/lymphocyte (G/L) ratio was associated with abnormal levels of sG-CSF. Logistic univariate analysis revealed that TIGs were a risk factor for lymph node metastasis (0.019) and TAMs were a risk factor for depth of invasion (0.029), but this was not confirmed in logistic multivariate analysis. In conclusion, IL-6, IL-8, sM-CSF and sG-CSF may indirectly promote tumor growth, progression and metastasis by changing the leukocyte populations in the blood and the tumor microenvironment.

A Case of Squamous Cell Carcinoma of the Lung That Produced Granulocyte Colony-Stimulating Factor and Interleukin-6

A 77-year-old woman visited our institution complaining of general fatigue. Chest radiography revealed masses in the upper and middle lung fields. Pathological findings for an endoscopic biopsy specimen revealed squamous cell carcinoma. High-grade fever developed and blood analyses revealed sustained elevated white blood cell count and C-reactive protein levels. Cytokine production by tumor cells was suspected; both serum granulocyte colony-stimulating factor (117 pg/mL; normal: <57.5 pg/mL) and interleukin-6 (83.5 pg/mL; normal: <2.41 pg/mL) levels were high. Immunohistochemical examination of biopsy specimens showed positive staining with antigranulocyte colony-stimulating factor and anti-interleukin-6 monoclonal antibodies. Diagnosis of a tumor that produced granulocyte colony-stimulating factor and interleukin-6 was established. The patient was administered best supportive therapy since she was not eligible for surgical treatment because of her poor respiratory function. She died from interstitial pneumonia exacerbation two months after this diagnosis. We present a female with squamous cell carcinoma of the lung that produced granulocyte colony-stimulating factor and interleukin-6.

Biomarkers associated with unresponsiveness to IVIG in children with Kawasaki disease

We have adopted DNA-microarray technology to analyze gene expression profiles in patients with Kawasaki Disease (KD). The results demonstrated that neutrophils in acute KD patients were not only expanded in number but also activated through the expression of a variety of late-stage granulocyte-specific genes such as polycythemia rubra vera 1 (PRV-1) and haptoglobin compared with febrile controls. In accordance with these findings, serum granulocyte colony-stimulating factor (G-CSF) levels were also higher in IVIG-resistant patients than those in responsive patients. These results might indicate evidences for dysregulated immunological pathways in KD patients and provide possible tools for diagnosis and prognostics of KD. We also found that high-dose IgG specifically and completely inhibited accelerated expression of KD-related cytokines such as G-CSF, IL-6 and IL-1β by HCAEC in response to TNF-α. The suppression of these cytokine genes correlated closely with functional inhibition of a transcription factor, C/EBP-δ. These findings suggest that the clinical effects of IVIG on KD patients are at least in part due to its direct anti-inflammatory effects on the coronary endothelium, which is a major lesion site in the pathogenesis of KD.

Granulocyte-colony stimulating factor-producing squamous cell carcinoma arising in ovarian mature cystic teratoma: A case report

Granulocyte-colony stimulating factor (G-CSF)-producing cancer has been reported to occur in various organs. It has an aggressive nature and shows resistance to conventional treatments, however, its clinical features are not well known because of the small number or reported cases. We report G-CSF-producing squamous cell carcinoma arising in malignant-transformed ovarian mature cystic teratoma. An 80-year-old woman underwent suboptimal surgical excision of stage IIIC ovarian cancer. Prior to the treatment, the patient presented severe granulocytosis and elevated serum G-CSF concentration. With the help of histopathological and immunohistochemical studies, we diagnosed this case to be a poorly differentiated squamous cell carcinoma developed in ovarian mature cystic teratoma, which highly expressed G-CSF. During radiation therapy, the patient died from rapid growth of residual tumor and peritoneal dissemination 2 months after surgery. This is the first case of G-CSF-producing squamous cell carcinoma arising in malignant-transformed ovarian mature cystic teratoma, and its prognosis was very poor.

Radioprotective effects of oral 17-dimethylaminoethylamino-17-demethoxygeldanamycin in mice: bone marrow and small intestine

BackgroundOur previous research demonstrated that one subcutaneous injection of 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) 24 hours (h) before irradiation (8.75 Gy) increased mouse survival by 75%. However, the protective mechanism of 17-DMAG is currently unknown. The present study aimed to investigate whether oral administration of 17-DMAG was also radioprotective and the potential role it may play in radioprotection.ResultsA single dose of orally pre-administered (24, 48, or 72 h) 17-DMAG (10 mg/kg) increased irradiated mouse survival, reduced body weight loss, improved water consumption, and decreased facial dropsy, whereas orally post-administered 17-DMAG failed. Additional oral doses of pre-treatment did not improve 30-day survival. The protective effect of multiple pre-administrations (2−3 times) of 17-DMAG at 10 mg/kg was equal to the outcome of a single pre-treatment. In 17-DMAG-pretreated mice, attenuation of bone marrow aplasia in femurs 30 days after irradiation with recovered expressions of cluster of differentiation 34, 44 (CD34, CD44), and survivin in bone marrow cells were observed. 17-DMAG also elevated serum granulocyte-colony stimulating factor (G-CSF), decreased serum fms-related tyrosine kinase 3 ligand, and reduced white blood cell depletion. 17-DMAG ameliorated small intestinal histological damage, promoted recovery of villus heights and intestinal crypts including stem cells, where increased leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) was found 30 days after irradiation.Conclusions17-DMAG is a potential radioprotectant for bone marrow and small intestine that results in survival improvement.

Localized Mucosal Response to Intranasal Live Attenuated Influenza Vaccine in Adults

Influenza virus infection is a major public health burden worldwide. Available vaccines include the inactivated intramuscular trivalent vaccine and, more recently, an intranasal live attenuated influenza vaccine (LAIV). The measure of successful vaccination with the inactivated vaccine is a systemic rise in immunoglobulin G (IgG) level, but for the LAIV no such correlate has been established. Seventy-nine subjects were given the LAIV FluMist. Blood was collected prior to vaccination and 3 days and 30 days after vaccination. Nasal wash was collected 3 days and 30 days after vaccination. Responses were measured systemically and in mucosal secretions for cytokines, cell activation profiles, and antibody responses. Only 9% of subjects who received LAIV seroconverted, while 33% of patients developed at least a 2-fold increase in influenza virus-specific immunoglobulin A (IgA) antibodies in nasal wash. LAIV induced a localized inflammation, as suggested by increased expression of interferon-response genes in mucosal RNA and increased granulocyte colony-stimulating factor (G-CSF) and IP-10 in nasal wash. Interestingly, patients who seroconverted had significantly lower serum levels of G-CSF before vaccination. Protection by LAIV is likely provided through mucosal IgA and not by increases in systemic IgG. LAIV induces local inflammation. Seroconversion is achieved in a small fraction of subjects with a lower serum G-CSF level.

Alterations of Circulating Endothelial Cell and Endothelial Progenitor Cell Counts around the Ovulation

Circulating endothelial cells (CECs) and progenitor cells (CEPs) have been intensively studied as a promising tool for treating ischemic diseases and monitoring cancer treatments, but how the menstrual cycle affects the variation in their counts remains unclear. The aims of the study were to determine the influence of the menstrual cycle on the number of CECs and CEPs and to investigate the association of their counts with circulating hormones and angiogenesis-associated factors. CEP and CEC counts by flow cytometry and the CellSearch system and circulating factor levels were measured eight times during the menstrual cycle in 18 volunteers. The menstrual cycle was divided into six phases based on hormone concentrations. CEP counts peaked in the periovulatory and middle luteal phases with a drop in the early luteal phase. CEC counts showed no significant variation. There were significant correlations between the CEP counts and the serum concentrations of estradiol (E2), LH, and granulocyte colony-stimulating factor (G-CSF) (P < 0.0001, P < 0.0001, and P = 0.01, respectively). The difference in CEP counts between two adjacent phases was significantly correlated with that in E2, LH, G-CSF, and serum vascular endothelial growth factor (P < 0.0001, P < 0.0001, P = 0.02, and P = 0.006, respectively). CEP counts peaked in the periovulatory and middle luteal phases, with a drop in the early luteal phase, and were correlated with serum E2, LH, and G-CSF concentrations. Consideration of the variation in CEP counts would be important for the clinical application of CEPs.

Temporal alteration of serum G-CSF and VEGF levels in perinatal asphyxia treated with head cooling

Objective: Granulocyte-colony stimulating factor (G-CSF) and vascular endothelial growth factor (VEGF) are thought to be associated with the pathophysiology of perinatal asphyxia. To clarify any such association, we analyzed the serum levels in neonates with perinatal asphyxia treated with head cooling.Study design: Temporal alterations of serum G-CSF and VEGF levels were measured within 24h of birth in five neonatal cases of severe asphyxia treated with head cooling, five neonatal cases without head cooling, and four healthy neonatal cases.Results: G-CSF in sera markedly increased and sustained in severely asphyxiated neonates treated with head cooling, while VEGF decreased and remained low.Conclusion: G-CSF and VEGF levels in sera might be associated with an early phase of brain protection after birth in severe asphyxia treated with head cooling.

Serum Granulocyte Colony-Stimulating Factor and Alzheimer’s Disease

Background: Granulocyte colony-stimulating factor (G-CSF) promotes the survival and function of neutrophils. G-CSF is also a neurotrophic factor, increasing neuroplasticity and suppressing apoptosis. Methods: We analyzed G-CSF levels in 197 patients with probable Alzheimer’s disease (AD) and 203 cognitively normal controls (NCs) from a longitudinal study by the Texas Alzheimer’s Research and Care Consortium (TARCC). Data were analyzed by regression with adjustment for age, education, gender and APOE4 status. Results: Serum G-CSF was significantly lower in AD patients than in NCs (β = –0.073; p = 0.008). However, among AD patients, higher serum G-CSF was significantly associated with increased disease severity, as indicated by lower Mini-Mental State Examination scores (β = –0.178; p = 0.014) and higher scores on the global Clinical Dementia Rating (CDR) scale (β = 0.170; p = 0.018) and CDR Sum of Boxes (β = 0.157; p = 0.035). Conclusions: G-CSF appears to have a complex relationship with AD pathogenesis and may reflect different pathophysiologic processes at different illness stages.

In Enterovirus 71 Encephalitis With Cardio-Respiratory Compromise, Elevated Interleukin 1 , Interleukin 1 Receptor Antagonist, and Granulocyte Colony-Stimulating Factor Levels Are Markers of Poor Prognosis

Enterovirus 71 (EV71) causes large outbreaks of hand, foot, and mouth disease (HFMD), with severe neurological complications and cardio-respiratory compromise, but the pathogenesis is poorly understood. We measured levels of 30 chemokines and cytokines in serum and cerebrospinal fluid (CSF) samples from Malaysian children hospitalized with EV71 infection (n = 88), comprising uncomplicated HFMD (n = 47), meningitis (n = 8), acute flaccid paralysis (n = 1), encephalitis (n = 21), and encephalitis with cardiorespiratory compromise (n = 11). Four of the latter patients died. Both pro-inflammatory and anti-inflammatory mediator levels were elevated, with different patterns of mediator abundance in the CSF and vascular compartments. Serum concentrations of interleukin 1β (IL-1β), interleukin 1 receptor antagonist (IL-1Ra), and granulocyte colony-stimulating factor (G-CSF) were raised significantly in patients who developed cardio-respiratory compromise (P = .013, P = .004, and P < .001, respectively). Serum IL-1Ra and G-CSF levels were also significantly elevated in patients who died, with a serum G-CSF to interleukin 5 ratio of >100 at admission being the most accurate prognostic marker for death (P < .001; accuracy, 85.5%; sensitivity, 100%; specificity, 84.7%). Given that IL-1β has a negative inotropic action on the heart, and that both its natural antagonist, IL-1Ra, and G-CSF are being assessed as treatments for acute cardiac impairment, the findings suggest we have identified functional markers of EV71-related cardiac dysfunction and potential treatment options.

Granulocyte colony-stimulating factor-producing squamous cell carcinoma of the lower gingiva: a case report

The present study summarizes our experience in treating a patient with a suspected granulocyte colony-stimulating factor (G-CSF)-producing squamous cell carcinoma (SCC) of the lower gingiva, which is a rather rare entity.A 56-year-old woman underwent surgical excision of palate leukoplakia in 1996. In 2009, however, a leukoplakic superficial tumor was detected in the lower left gingiva, for which the patient underwent gingivectomy. This was subsequently diagnosed as SCC. The patient also underwent superselective arterial injection chemotherapy combined with radiotherapy, after local recurrence was observed. The patient was subsequently found to have bone metastasis. After chemotherapy combined with radiotherapy, the patient underwent segmental resection of the lower left jaw, left supraomohyoid neck dissection, and lower jaw reconstruction using titanium plates. Resection of the left femoral tumor and left total knee replacement were also performed. Computed tomography scan performed 1 month after the surgeries revealed multiple lung, liver, spine, and subcutaneous metastases. The patient also exhibited a sudden increase in her white blood cell (WBC) count and a fever that could not be alleviated, despite treatment with antibacterial drugs. A G-CSF-producing tumor was therefore suspected. Serum G-CSF level was high at 250 pg/ml.The patient's WBC count increased to 32 × 103/ml and her general condition suddenly deteriorated, and she died as a result of multiple organ failure. A final diagnosis of G-CSF-producing SCC of the lower gingiva was made based on the patient's clinical course.

Deciduosis can cause remarkable leukocytosis and obscure abdominal pain

Remarkable leukocytosis with obscure abdominal pain during pregnancy is clinically challenging for obstetricians. A 31-year-old pregnant woman developed persistently elevated white blood cell (approximately 30 000/µL) and C-reactive protein (3.0 mg/dL) with occasional moderate abdominal pain. At 29 gestational weeks, she underwent emergency cesarean section due to suspected abruptio placentae. Hemoperitoneum was observed with extensive hemorrhagic nodules on the peritoneal and omental surfaces. White blood cells rose 87200/µL, and C-reactive protein peaked at 44.9mg/dL after surgery. Pathologically, biopsies showed deciduosis, and decidual cells on the omental surface showed immunohistochemical staining for granulocyte colony-stimulating factor (G-CSF). Serum G-CSF concentration was 339 pg/mL at 28 weeks, and that of ascites was 312 000 pg/mL at cesarean section. G-CSF-producing deciduosis can induce leukocytosis as well as abdominal pain during pregnancy and postpartum.

Effect of midazolam and propofol on serum VEGF concentration and G-CSF-induced bone marrow stem cell mobilization after acute myocardial infarction in rats

Objective To investigate the effect of propofol and midazolam on the serum vascular endothe lial growth factor (VEGF) concentration and granulocyte colony-stimulating factor (G-CSF)-induced bone marrow stem cell (BMSC) mobilization after acute myocardial infarction in rats.Methods Thirty-six male Wistar rats,weighing 250-280 g,were anesthetized with intraperitonel 1％ pentobarbital 45 mg/kg.Acute myocardial infarct was induced by ligation of left anterior descending branch of coronary artery.BMSC mobilization was induced by intraperitoneal injection of G-CSF for 5 days.On 7th day after BMSC mobilization,the rats were equally and randomly divided into three groups:G-CSF group (group G),midazolam group (group M) and propofol group (group P).In group G,normal saline was continuously infused via the femoral vein at a rate of 0.5 ml/h for 6 h.In group M,midazolam was infused via the femoral vein at 0.05 mg· kg - 1 · h- 1 for 6 h.In group P,propofol was infused via the femoral vein at 5 mg·kg1 -h-1 for 6 h.Blood samples were obtained from the femoral vein after administration to determine the number of CD34+ monocyte (CD34+ MNC) and endothelial progenitor cells (EPCs) by flow cytometry and the serum concentration of VEGF by ELISA.Six rats from each group were chosen 4 weeks after myocardial infarction for measurement of the left ventricular end-diastolic pressure (LVEDP) and ± dp/dtmax Results Compared with group G,the number of CD34 + MNC and EPCs,the serum concentration of VEGF,and the absolute value of - dp/dtmax were significantly increased,while LVEDP was significantly decreased in group ( P ＜0.05),and LVEDP was significantly decreased,and the absolute value of - dp/dtmax was significantly increased in group P ( P ＜ 0.05).Compared with group P,the number of CD34+ MNC and EPCs,the serum concentration of VEGF,and the absolute value of - dp/dtmax were significantly increased,while LVEDP was significantly decreased in group M (P ＜ 0.05).Conclusion Midazolam can promote the release of VEGF,strengthen G-CSF-induced BMSC mobilization and improve the cardiac function after acute myocardial infarction in rats.Propofol can not promote the release of VEGF and produce G-CSF-induced BMSC mobilization after acute myocardial infarction in rats. Key words: Midazolam; Propofol; Myocardial infarction; Vascular endothelial growth factors; Granulocyte colony-stimulating factor; Stem cells

Uterine Leiomyosarcoma Producing Granulocyte Colony Stimulating Factor

Uterine leiomyosarcoma associated with the paraneoplastic production of granulocyte-colony stimulating factor (GCSF) is extremely rare. No case has been reported to date in the English literature. We describe a case of a 56-year-old female with recurrent uterin leiomyosarcoma, associated with leukocytosis (19100/mm) and an elevated serum GCSF (33.0 pg/ml). Tumore histology was consistent with a well differentiated leiomyosarcoma with marked neutrophilic infiltration of the lung and spleen metastases. tumor cells were distinctly positive for GCSF on immunohistochemistry. These findings confirmed the diagnosis of a GCSF-producting uterine leiomyosarcoma with a paraneoplastic leukocytosis.

Anaplastic Transformation of Follicular Thyroid Carcinoma in a Metastatic Skeletal Lesion Presenting with Paraneoplastic Leukocytosis

Anaplastic transformation of differentiated thyroid carcinoma (DTC) is a rare event with a poor clinical outcome. It usually occurs in the primary site or in regional lymph nodes, but rarely in distant metastatic lesions. A 55-year-old woman with persistent pain in the left hip joint visited our hospital. She had a history of DTC that had been surgically removed 12 years earlier. Clinical images showed a tumorous mass in the left pelvis, indicative of bone metastasis. The patient underwent surgery to remove the tumor and remained stable until local recurrence was found 5 weeks after the surgery. The patient subsequently underwent radiation therapy; however, she died of respiratory failure due to lung metastases 2 months after the surgery for the recurrent lesion. The surgical specimens were diagnosed as anaplastic thyroid carcinoma, indicating that anaplastic transformation of thyroid follicular carcinoma occurred in the metastatic skeletal lesion. In addition, the patient had an unusually high white blood cell count throughout the course. Based on elevated serum granulocyte colony-stimulating factor (G-CSF) levels and positive immunostaining for G-CSF in the surgical specimens, the patient was diagnosed with paraneoplastic leukocytosis. To our knowledge, this is the first case of anaplastic transformation of DTC arising in a metastatic bone lesion described in the literature. In addition, the present case also exhibited severe leukocytosis accompanied by elevated serum G-CSF levels. Clinicians should be aware of the possibility of this occurring in their patients with DTC, as this development calls for a rapid change from observational follow-up to aggressive treatment.