Serum Colony-stimulating Factor Research Articles

Safety and efficacy of AMG 820, an anti-colony-stimulating factor 1 receptor antibody, in combination with pembrolizumab in adults with advanced solid tumors

BackgroundTo determine the safety and efficacy of the anti-colony-stimulating factor 1 receptor (anti-CSF1R) monoclonal antibody AMG 820 in combination with pembrolizumab in patients with select solid tumors.Patients and methodsPatients had...

Expression of serum colony stimulating factor 1 in patients with acute-on-chronic liver failure and its influence on prognosis

Expression of serum colony stimulating factor 1 in patients with acute-on-chronic liver failure and its influence on prognosis

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.

Abstract 3206: Multistage vectored siRNA targeting ataxia-telangiectasia mutated for breast cancer therapy.

Abstract The ataxia-telangiectasia mutated (ATM) protein plays a central role in DNA damage response and cell cycle checkpoints, and may be a promising target for cancer therapy if normal tissue toxicity could be avoided. Our strategy to target ATM for breast cancer therapy involves the use of liposomal-encapsulated, gene-specific ATM small interfering RNA (siRNA) delivered with a well-characterized porous silicon-based multistage vector (MSV) delivery system (MSV/ATM). Here we have shown that biweekly treatment of MSV/ATM suppressed ATM expression in tumor tissues, and consequently inhibited growth of MDA-MB-231 orthotopic tumor in nude mice. At the therapeutic dosage, neither free liposomal ATM siRNA nor MSV/ATM triggered acute immune response in BALB/c mice, including changes in serum cytokines, chemokines or colony-stimulating factors. Weekly treatments of mice with free liposomal ATM siRNA or MSV/ATM for 4 weeks did not cause significant changes in body weight, hematology, blood biochemistry, or major organ histology. These results indicate that MSV/ATM is biocompatible and efficacious in inhibiting tumor growth, and that further preclinical evaluation is warranted for the development of MSV/ATM as a potential therapeutic agent. Citation Format: Rong Xu, Yi Huang, Jun Hua Mai, Guo Dong Zhang, Xiao Jing Guo, Xiao Jun Xia, Eugene J Koay, Xue Wu Liu, Mauro Ferrari, Hai Fa Shen. Multistage vectored siRNA targeting ataxia-telangiectasia mutated for breast cancer therapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3206. doi:10.1158/1538-7445.AM2013-3206

Paraneoplastic neurological and hematological syndromes associated with prostate cancer

Paraneoplastic neurological syndromes are defined as the remote effects of cancer on the nervous system. Here we report a 68-year-old man who initially presented with worsening paresthesia in the lower extremities. Although the culprit lesion remained to be identified, he coincidentally had diagnosis of prostate cancer by an annual prostate-specific antigen examination. Leukocytosis and elevated granulocyte colony-stimulating factor in serum were also detected. Neurological symptoms and leukocytosis improved after initiation of androgen-deprivation therapy followed by external beam radiotherapy. A total of 9 months after treatment, the patient showed no evidence of cancer recurrence or neurological signs. Paraneoplastic neurological syndromes are rare in prostate cancer and therefore have received little attention. We should be aware that when paraneoplastic neurological syndromes occur, they usually occur as the first sign of or during progression of prostate cancer. Furthermore, we should take into account the existence of malignancy when the cause of neurological symptoms cannot be specified.

Endothelial precursor cells promote angiogenesis in hepatocellular carcinoma

To investigate the role of bone marrow-derived endothelial progenitor cells (EPCs) in the angiogenesis of hepatocellular carcinoma (HCC). The bone marrow of HCC mice was reconstructed by transplanting green fluorescent protein (GFP) + bone marrow cells. The concentration of circulating EPCs was determined by colony-forming assays and fluorescence-activated cell sorting. Serum and tissue levels of vascular endothelial growth factor (VEGF) and colony-stimulating factor (CSF) were quantified by enzyme-linked immunosorbent assay. The distribution of EPCs in tumor and tumor-free tissues was detected by immunohistochemistry and real-time polymerase chain reaction. The incorporation of EPCs into hepatic vessels was examined by immunofluorescence and immunohistochemistry. The proportion of EPCs in vessels was then calculated. The HCC model was successful established. The flow cytometry analysis showed the mean percentage of CD133CD34 and CD133VEGFR2 double positive cells in HCC mice was 0.45% ± 0.16% and 0.20% ± 0.09% respectively. These values are much higher than in the sham-operation group (0.11% ± 0.13%, 0.05% ± 0.11%, n = 9) at 14 d after modeling. At 21 d, the mean percentage of circulating CD133CD34 and CD133VEGFR2 cells is 0.23% ± 0.19%, 0.25% ± 0.15% in HCC model vs 0.05% ± 0.04%, 0.12% ± 0.11% in control. Compared to the transient increase observed in controls, the higher level of circulating EPCs were induced by HCC. In addition, the level of serum VEGF and CSF increased gradually in HCC, reaching its peak 14 d after modeling, then slowly decreased. Consecutive sections stained for the CD133 and CD34 antigens showed that the CD133+ and CD34+ VEGFR2 cells were mostly recruited to HCC tissue and concentrated in tumor microvessels. Under fluorescence microscopy, the bone-marrow (BM)-derived cells labeled with GFP were concentrated in the same area. The relative levels of CD133 and CD34 gene expression were elevated in tumors, around 5.0 and 3.8 times that of the tumor free area. In frozen liver sections from HCC mice, cells co-expressing CD133 and VEGFR2 were identified by immunohistochemical staining using anti-CD133 and VEGFR2 antibodies. In tumor tissue, the double-positive cells were incorporated into vessel walls. In immunofluorescent staining. These CD31 and GFP double positive cells are direct evidence that tumor vascular endothelial cells (VECs) come partly from BM-derived EPCs. The proportion of GFP CD31 double positive VECs (out of all VECs) on day 21 was around 35.3% ± 21.2%. This is much higher than the value recorded on day 7 group (17.1% ± 8.9%). The expression of intercellular adhesion molecule 1, vascular adhesion molecule 1, and VEGF was higher in tumor areas than in tumor-free tissues. Mobilized EPCs were found to participate in tumor vasculogenesis of HCC. Inhibiting EPC mobilization or recruitment to tumor tissue may be an efficient strategy for treating HCC.

Therapy options in pulmonary alveolar proteinosis

Pulmonary alveolar proteinosis is a rare condition characterized by the accumulation of lipoproteinaceous material within the airspaces, resulting in impaired gas transfer, and clinical manifestations ranging from asymptomatic to severe respiratory failure. To the best of the authors' knowledge, there are only a few conditions whose natural history has been so dramatically changed by the influence of advances in basic science, clinical medicine, and translational research in therapeutic approaches. Whole-lung lavage is the current standard of care and it plays a critical role as a modifier factor of the natural history of proteinosis. That notwithstanding, the identification of autoantibodies neutralizing granulocyte-macrophage colony-stimulating factor in serum and lung of patients affected by the form of proteinosis previously referred to as idiopathic, has opened the way to novel therapeutic options, such as supplementation of exogenous granulocyte-macrophage colony-stimulating factor, or strategies aimed at reducing the levels of the autoantibodies. The aim of this paper is to provide an updated review of the current therapeutic approach to proteinosis.

Neutrophilic dermatoses with acute myeloid leukemia associated with an increase of serum colony-stimulating factor

We report a case of acute myeloid leukemia with folliculitis, Sweet's syndrome, and neutrophilic panniculitis after remission induction chemotherapy for acute myeloid leukemia. The level of endogenous granulocyte colony-stimulating factor was closely associated with disease activity.

Evaluation of Tumor Necrosis Factor-Alpha and Granulocyte Colony-Stimulating Factor Serum Levels in Lead-Exposed Smoker Workers

Inorganic lead (Pb) is able to modulate the immune response even at low to moderate exposure levels. It inhibits in vitro and in vivo activities of neutrophil leucocytes and influences their blood count in humans. Neutrophil functions are governed by a number of cytokines. Pb has been shown to affect leukocyte production of some of these cytokines in vitro. The objective of this study is to assess serum tumor necrosis factor-alpha (TNF-alpha) and granulocyte colony-stimulating factor (G-CSF) levels of thirty-three male lead-exposed (E) workers at a lead recycling plant as compared with twenty-eight male non-exposed (NE) workers at a food processing plant, whose current smoking habit was known. Serum TNF-alpha and G-CSF levels were measured by a quantitative sandwich enzyme immunoassay. Blood lead levels (Pb-B) were significantly higher in E (geometric mean (GM) 30.7 microg/dl, GSD 1.7; min-max: 9.1-81.6 microg/dl) workers than controls (GM 3.6 microg/dl, GSD 1.7; min-max: 1.0-11.0 microg/dl). E workers had significantly higher serum TNF-alpha (median: 107.1; min-max: 11.1-623.0 pg/ml) and G-CSF levels (median: 53.0, min-max: 31.1-197.0 pg/ml) than NE workers (TNF-alpha: median: 12.0; min-max: 9.4-18.8 pg/ml; G-CSF: median: 34.3, min-max: 25.1-52.2 pg/ml). In particular, the TNF-alpha level was shown to be significantly influenced by lead exposure and smoking habit, as well as by interaction between these two factors. Both serum TNF-alpha and G-CSF levels were correlated with Pb-B and absolute neutrophil count. This study is the first to detect higher serum levels of G-CSF in E over NE workers. Our data confirm that exposure to low to medium doses of lead may interfere in the complex cytokine network involved in inflammation, especially in workers who are current smokers.

Impaired salivary gland function in NOD mice: Association with changes in cytokine profile but not with histopathologic changes in the salivary gland

To characterize the chronologic disease course and possible interrelationships between salivary gland inflammation, hyposalivation, and cytokine levels in NOD mice, a model for Sjögren's syndrome (SS). NOD mice of different ages were used to mimic different disease stages of SS. Histopathologic findings and rates of salivary secretion were compared between 8-week-old, 17-week-old, and 24-week-old female mice. In addition, 10 cytokines were analyzed in serum and saliva obtained from NOD and BALB/c mice. In NOD mice, the salivary flow rate did not change between 8 weeks and 17 weeks of age, while a significant decrease in the salivary flow rate occurred between 17 weeks and 24 weeks of age (P < 0.001). In contrast, significant histopathologic changes in the salivary glands occurred before 17 weeks of age. Chronic inflammatory cell infiltrates were characterized by T and B cell infiltration. Interestingly, in one-third of the mice, proliferating cells were observed in the focal infiltrates. Significant changes in the levels of interleukin-2 (IL-2), IL-5, and granulocyte-macrophage colony-stimulating factor in serum, and in the levels of IL-4 and tumor necrosis factor alpha (TNFalpha) in saliva occurred contemporarily with the decrease in salivary flow. Correlation analyses revealed a negative association between salivary secretion and the levels of IL-4, interferon-gamma, and TNFalpha in saliva obtained from NOD mice, while the correlation with inflammatory changes in the glands was consistently weak. Consistent with previous findings, our results indicate at least 2 phases of SS-like disease in NOD mice. Hyposalivation was preceded by inflammatory changes in the salivary glands, whereas abrupt changes in secretion occurred without significant progression of inflammation. Changes in cytokine levels are an indication of the mechanisms involved in the adaptive immune response in the transition from early to overt disease.

Leishmania donovani amastigote components-induced colony-stimulating factors production

Increased hematopoiesis, driven by colony-stimulating factors (CSFs), is known to occur in infectious diseases. However, whether Leishmania donovani component(s) can directly induce the synthesis and secretion of CSFs is not known. We report that L. donovani amastigote antigens soluble in culture medium (LDAA; 0.01–10 mg/kg), injected intravenously in BALB/c mice, induced the production of serum CSFs; maximum induction (128>16 colonies) occurred at 1 mg/kg. In vitro also, LDAA (0.01–1 mg/ml) induced mouse peritoneal macrophages (MØs) to elaborate CSFs in the conditioned medium (CM); 0.1 mg/ml LDAA appeared optimal (68±9 colonies). Both in vivo and in vitro, the kinetics of CSF production were similar with peak response occurring 24 h after stimulation and return to background levels by 72 h. A predominant ∼12 kDa LDAA protein (LDAA-12) also induced CSF production, both in serum and CM, in a dose-and time-dependent manner . Rabbit anti-LDAA-12 antibody significantly ( p<0.05) reduced both the LDAA-and LDAA-12-induced CSF production, in vitro. Functionally, the LDAA-12-induced CSFs, both in the serum and CM, appeared to be similar as they supported the formation of granulocyte (G), MØ (M) and GM colonies, in vitro, in similar proportion; GM colonies were maximum (>80%). Further, LDAA-12 induced significantly ( p<0.05) high GM-CSF levels both in serum and CM (19±3 and 15±2 ng/ml, respectively), as compared to the controls. Neutralizing (100%) goat anti-mouse tumour necrosis factor-α (TNF-α) immunoglobulin G did not affect the LDAA-12-induced CSF production by MØs, indicating it to be TNF-α-independent. LDAA-12 induced de novo CSF production, as MØs co-treated with LDAA-12 and cycloheximide (50 μg/ml) did not elaborate CSFs. The CSF-inducing capability of LDAA-12 appeared to be heat (70 C; 1 h)-labile, destroyed by proteases (pronase E and trypsin) and was unaffected by sodium periodate treatment. In LDAA-12-treated mice, the splenic and femur colony forming unit-GM counts showed a maximum of 2.2- and 1.9-fold increase, respectively, as compared to the controls. These data are the first to directly demonstrate that L. donovani amastigote components can induce the production of CSFs that may play important role(s) in the pathogenesis of visceral leishmaniasis.

Kostmann disease—infantile genetic agranulocytosis: historical views and new aspects

The results in the main reports on infantile genetic agranulocytosis or Kostmann Syndrome are summarized. New views on the pathogensis of the syndrome are given in a recent paper by Pütsep et al. Kostmann syndrome may cause early onset Group B streptococcal neonatal sepsis as reported in this issue of Acta Paediatrica (9). Patients with Kostmann Syndrome who are successfully treated for agranulocytosis with serum colony stimulating factor remain deficient in cathelin-LL-37, a peptide antibiotic, which is normally present in neutrophils and saliva. This deficiency may explain that patients who are successfully treated for agranulocytosis continue to suffer from oral infections such as chronic periodontitis.

Low Fcγ receptor III and high granulocyte colony-stimulating factor serum levels correlate with the risk of infection in neutropenia due to Felty’s syndrome or systemic lupus erythematosus

PurposeTo determine whether serum levels of soluble Fcγ receptor III and granulocyte colony-stimulating factor (G-CSF) are associated with the risk of infection in patients with neutropenia due to Felty’s syndrome or systemic lupus erythematosus. Subjects and methodsSerum levels of G-CSF and soluble Fcγ receptor III were measured by enzyme-linked immunosorbent assays in 13 patients with neutropenia due to Felty’s syndrome, 10 patients with neutropenia due to systemic lupus erythematosus, and 41 controls with normal leukocyte counts (25 with systemic lupus erythematosus, 16 with rheumatoid arthritis). We calculated the area under the receiver operating characteristic (ROC) curves for the absolute neutrophil count, soluble Fcγ receptor III levels, and G-CSF levels. ResultsNine of the neutropenic patients (7 with Felty’s syndrome, 2 with lupus) had one or more infections within 3 months before and after blood samples were obtained. Absolute neutrophil counts were similar in neutropenic patients who did or did not have infections. However, the median level of soluble Fcγ receptor III (63 vs. 126 arbitrary units, P = 0.005) was significantly lower among patients who developed infections, whereas the median level of G-CSF (90.9 vs. 53.3 pg/mL, P = 0.04) was significantly higher compared with patients without infections. The area under the ROC curve was 0.58 (P = 0.49) for the absolute neutrophil count, 0.84 (P = 0.007) for soluble Fcγ receptor III levels, and 0.73 (P = 0.03) for G-CSF levels. ConclusionIn patients with chronic neutropenia due to rheumatic diseases, low soluble Fcγ receptor III levels and elevated G-CSF levels are better indicators of the risk of infection than is the neutrophil count.

Granulocyte colony-stimulating factor serum and urine concentrations in neutropenic neonates before and after intravenous administration of recombinant granulocyte colony-stimulating factor.

Recombinant granulocyte colony-stimulating factor (rG-CSF) has been suggested as a treatment for certain varieties of neonatal neutropenia, but little is known about the pharmacologic disposition of rG-CSF in that population. Ten neutropenic neonates were treated with rG-CSF, 10 micrograms/kg intravenously once daily for 3 to 5 days. Serum and urine samples were obtained before rG-CSF dosing and at intervals thereafter for G-CSF quantification by enzyme-linked immunosorbent assay. Five of the neutropenic neonates (termed group 1) were not infected but likely had hyporegenerative neutropenia (4 were born after pregnancy-induced hypertension/intrauterine growth restriction, and 1 had Rh hemolytic disease). Five other infants (group 2) had neutropenia accompanying bacterial sepsis and shock. Before receiving the first dose of rG-CSF, endogenous G-CSF serum and urine concentrations were relatively low in group 1, averaging 130 pg/mL (range: 48-209) in serum and 53 pg/mL (range: 15-141) in urine. Serum concentrations immediately before the final dose were much higher (range: 81-24 835 pg/mL), whereas urine concentrations were unchanged (range: <7 pg/mL-126 pg/mL). In group 2 patients, before receiving the first-dose of rG-CSF, endogenous concentrations were very high, averaging 59 575 pg/mL (range: 20 028-98 280) in serum and 3189 pg/mL (range: 23-4770) in urine. Predose serum concentrations before the final dose (range: 427-14 460 pg/mL) were lower than before the first dose. The area under the concentration curve after the first dose of rG-CSF administration in group 1 was significantly lower than after the first dose in group 2, but no difference in area under the concentration curve was observed between groups 1 and 2 after the last dose of rG-CSF. The principal means of clearing G-CSF from the serum is by saturable binding to specific G-CSF receptors (G-CSF-Rs). Therefore, the very high G-CSF serum and urine concentrations of group 2 patients before the first rG-CSF dose implies that their G-CSF-Rs were saturated before the dose was given. We speculate that if G-CSF-Rs are saturated with endogenous G-CSF, treatment with rG-CSF will add little or nothing to the granulocytopoietic effort. On this basis, we judge that neonates with septic shock and neutropenia are unlikely to derive benefit from rG-CSF administration.

Protective effect of swerchirin on hematopoiesis in 60Co-irradiated mice.

The protective effect of swerchirin, a purified xanthone isolated from whole herb of Swertia calycina Franch. on hematopoiesis was investigated. A significant increase of colony formation in the spleen (colony forming unit in spleen = CFU-S) of mice irradiated with 550 rad 60Co gamma-rays and an enhancement of proliferative response of BMC to rmGM-CSF treated with swerchirin [10 mg/kg, 3 time/wk, i.p.] was observed. After introduction of swerchirin [10 mg/kg, i.p. once] a significant increase in the number of peripheral blood leukocytes and a rise in the serum of colony stimulating factor (CSF) were also confirmed. The types of CSF in serum were M-CSF and other hematopoietic growth factors, which were confirmed using McAb of IL-3, GM-CSF and PcAb of M-CSF. These beneficial effects of swerchirin on hematopoiesis may be related to its activity inducing CSFs and other hematopoietic growth factors, and warrant further evaluation of its usefulness.

Serum levels of macrophage colony-stimulating factor-1 in cervical human papillomavirus infection and intraepithelial neoplasia

Objective: Our goal was determine the correlation between serum colony stimulating factor-1 levels, cervical human papillomavirus infection, and dysplasia. Study Design: Serum samples were obtained from control subjects from the United States and from a group of Panamanian women. Members of the latter group fell into 3 categories: those who serve as Panamanian control subjects and who test negative for human papillomavirus (n = 10); those who are high risk by history and test positive for human papillomavirus types 16/18 and 30s (n = 10); and those with the same high-risk history with biopsy-proven cervical intraepithelial neoplasia (n = 8). Serum colony-stimulating factor-1 levels were determined using enzyme-linked immunosorbent assay. Data were analyzed with the Student-Newman-Keuls and t tests. Results: Mean serum colony-stimulating factor-1 levels of patients with a positive test result for human papillomavirus (1166 ± 949 pg/mL) and cervical intraepithelial neoplasia (1295 ± 314 pg/mL) were higher than those of control subjects from the United States (584 ± 237 pg/mL) and those of Panamanian control subjects (520 ± 229 pg/mL). Statistical analysis revealed the concentration of colony-stimulating factor in patients with positive test results for human papillomavirus or cervical intraepithelial neoplasia were significantly higher than in control groups. In addition, combining patients with human papillomavirus with those who have cervical intraepithelial neoplasia results in a group that has significantly higher colony-stimulating factor levels compared with control subjects. Conclusions: Both high-grade cervical dysplasia and high-risk human papillomavirus infection are associated with higher mean serum colony-stimulating factor levels, suggesting a possible role for colony-stimulating factor-1 in cervical neoplasia. Further studies are needed to understand the mechanism of colony- stimulating factor activation in human papillomavirus infection. This may assist in designing therapeutic approaches for the management of this disease. (Am J Obstet Gynecol 1999;180:28-32.)

Colony Stimulating Factor-Inducing Activity of IsoflavoneC-Glucosides from the Bark ofDalbergia monetaria

To obtain immunomodulating substances from Amazonian medicinal plants, hot water extracts from 21 samples available commercially were tested in terms of mitogenic and colony-stimulating factor (CSF)-inducing activities. Among them, Dalbergia monetaria exhibited the highest CSF-inducing activity. Orobol 8-C-glucoside (OCG-8) and orobol 6-C-glucoside (OCG-6) were isolated from the bark of D. monetaria as major constituents. The CSF-inducing activity of OCG-8 was higher than that of OCG-6 and a dose-dependent manner at a range of 0.1-10 mg/mouse. Serum CSF production induced by an intraperitoneal (i.p.) injection with 1 mg OCG-8 reached a peak at 4-6 h later, suggesting that OCG-8 would act on hematopoietic system.

Changes in macrophage colonystimulating factor concentration in serum and follicular fluid in in-vitro fertilization and embryo transfer cycles

Objective: To evaluate the changes of macrophage colony-stimulating factor concentration in serum and compare macrophage colony-stimulating factor concentration in follicular fluid (FF) through IVF-ET cycles. Design: Sera and the matched FFs were collected serially through the IVF-ET cycles and analyzed retrospectively with respect to macrophage colony-stimulating factor concentration. Setting: Department of Obstetrics and Gynecology of Kumamoto University Hospital. Patient(s): Ninety-four women underwent 129 cycles of ovulation induction by using GnRH agonist (GnRHa)-hMG-hCG for IVF-ET program. Intervention(s): Serum and FF macrophage colony-stimulating factor concentrations were measured by ELISA. Main Outcome Measure(s): Concentrations of macrophage colony-stimulating factor in serum and FF. Result(s): Serum macrophage colony-stimulating factor concentration was gradually increased throughout ovarian stimulation, and reached a peak from the day of oocyte retrieval to 2 days after oocyte retrieval, whereas no significant change in macrophage colony-stimulating factor was observed in cases of poor ovarian response to hMG. The macrophage colony-stimulating factor concentration in follicles was significantly higher than that in sera on the day of oocyte retrieval, and the concentrations in follicles from which oocyte could be retrieved were significantly higher than those from which oocyte could not be retrieved. Conclusion(s): These results suggest that gonadotropins lead to an increase in ovarian macrophage colony-stimulating factor production, and that this macrophage colonystimulating factor production in response to hMG administration is lost in poor ovarian responders. Thus, macrophage colony-stimulating factor may play an important role in the process of follicular maturation and ovulation as an intraovarian regulator.

Affinity chromatography with immunochemical detection applied to the analysis of human methionyl granulocyte colony stimulating factor in serum.

An on-line, automated, HPLC method was developed for the separation and detection of recombinant human methionyl granulocyte colony stimulating factor (GCSF) and GCSF modified with poly(ethylene glycol) (PEG-GCSF) in rat serum. The automated method consists of an initial immunoaffinity chromatography step, a microbore reverse phase separation, and postcolumn immunochemical detection. Calibration curves were constructed with a lower limit of 1.5 ng of GCSF (80 fmol) and 7.5 ng of PEG-GCSF in 120 microL of rat serum. In vivo serum samples from rats dosed with PEG-GCSF were also analyzed. The development of the method is discussed as well as its general application to the detection of metabolites of recombinant proteins in body fluids.

Macrophage colony-stimulating factor 1, a clinically useful tumor marker in endometrial adenocarcinoma: Comparison with CA 125 and the aminoterminal propeptide of type III procollagen

OBJECTIVE: We investigated the clinical utility of macrophage colony-stimulating factor 1 versus CA 125 and the aminoterminal propeptide of type III procollagen in endometrial carcinoma. STUDY DESIGN: Serum levels of the three substances were measured in 159 patients with untreated endometrial adenocarcinoma and in 24 patients treated with cytotoxic chemotherapy for recurrent endometrial adenocarcinoma. RESULTS: Initial concentrations of colony-stimulating factor 1, CA 125, and the aminoterminal peptide of type III procollagen were above the normal range in 73%, 11%, and 27%, respectively, of the patients. Colony-stimulating factor 1 levels correlated with those of the aminoterminal peptide of type III procollagen ( r = 0.3, p = 0.002) and CA 125 ( r = 0.20, p = 0.036) in the total group and with those of the aminoterminal peptide of type III procollagen in stage I and II patients ( r = 0.3, p = 0.0023). Colony-stimulating factor 1 levels correlated significantly with tumor grade, whereas those of CA 125 and the aminoterminal peptide of type III procollagen correlated more closely with clinical stage. Mean colony-stimulating factor 1 levels (9.6 vs 7.7 ng/ml, p = 0.04) and the frequency of elevated CA 125 levels (31% vs 8%, p = 0.048) were higher in patients with poor prognosis than in those with good prognosis. Colony-stimulating factor 1, the aminoterminal peptide of type III procollagen, and CA 125 levels were useful in monitoring clinical behavior of the disease in 88%, 79%, and 63% of the cases, respectively. Levels of all three markers rose with disease progression, whereas colony-stimulating factor 1 and the aminoterminal peptide of type III procollagen fell with clinical responses to therapy. CONCLUSION: Elevated serum colony-stimulating factor 1 levels were the most accurate indicator of the presence and activity (progression, stabilization, or regression) of primary or recurrent disease. Accuracy was not further enhanced by measurement of CA 125 or the aminoterminal peptide of type III procollagen levels.