Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a case of successfully treated multifocal pulmonary Rhizomucor pusillus, a condition which has previously been universally fatal. A 77 year-old man had a background of chronic neutropenia due to hairy-cell leukemia, splenectomy, corticosteroid therapy and an obstructing left ureteric transitional-cell carcinoma. He was successfully treated with 3 months of high-dose liposomal amphotericin B and 7 months of granulocyte-macrophage colony-stimulating factor. Treatment was complicated by mild reversible deterioration of renal function. There was a near complete radiological response to the therapy at 6 months and the patient remains well 20 months following diagnosis of R. pusillus and 13 months following cessation of treatment.
Leuk Lymphoma
PMID:Cure of pulmonary Rhizomucor pusillus infection in a patient with hairy-cell leukemia: role of liposomal amphotericin B and GM-CSF. 1191 24

The outcome of a formulary interchange from filgrastim to sargramostim for the amelioration of neutropenia for outpatients receiving myelosuppressive chemotherapy was evaluated. The pharmacy department at the James Graham Brown Cancer Center of the University of Louisville Hospital implemented a therapeutic interchange program by following the Joint Commission on Accreditation of Healthcare Organizations performance methodology, incorporating four key elements: plan, do, check, and act. After the pharmacy and therapeutics committee agreed that filgrastim and sargramostim are therapeutically equivalent, the pharmacy initiated the interchange, with a commitment to collect outcomes data to analyze the impact of the program on patient outcomes. Inclusion criteria included patient age of > or = 18 years, the presence of solid tumors or lymphoma, and current treatment with traditional chemotherapy. Patient demographics and cycle-specific data were collected for 31 patients receiving sargramostim and 20 patients receiving filgrastim from August 2000 to July 2001. Absolute neutrophil counts (ANCs) were measured before initiating and after discontinuing colony-stimulating factors. The majority (70%) of all growth factor use was initiated within one to four days of the last chemotherapy dose. No appreciable difference was found between agents for median ANC at any measured time point. The majority of patients exceeded the target ANC of 1500 cells/mm3 at the time of growth factor discontinuation. There were no significant differences in the number of patients that had adverse effects or in the number of cycles resulting in an adverse event between groups. Sargramostim demonstrated a 21% cost savings over filgrastim ($1036 versus $1318, respectively). The formulary switch from filgrastim to sargramostim resulted in a significant cost savings for the institution without increasing incidence of adverse effects and negative outcomes associated with growth factor use.
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PMID:Formulary management of colony-stimulating factors. 1194 11

B-cell lymphomas express tumor-specific immunoglobulin, the variable regions of which [idiotype (Id)] can serve as a target for active immunotherapy. Promising results have been obtained in clinical studies of Id vaccination using Id proteins.However, Id protein is laborious and time-consuming to produce. DNA vaccination is an attractive alternative for delivering Id vaccines, because Id DNA can be rapidly isolated by PCR techniques. DNA coding for lymphoma Id can provide protective immunity in murine models. In the present study, we performed a Phase I/II clinical trial to study the safety and immunogenicity of naked DNA Id vaccines in 12 patients with follicular B-cell lymphoma. The DNA encoded a chimeric immunoglobulin molecule containing variable heavy and light chain immunoglobulin sequences derived from each patient's tumor, linked to the IgG2a and kappa mouse immunoglobulin (MsIg) heavy- and light-chain constant regions chains, respectively. Patients in remission after chemotherapy received three monthly i.m. injections of the DNA in three dose escalation cohorts of four patients each (200, 600, and 1800 micro g). After vaccination, 7 of 12 patients mounted either humoral (n = 4) or T-cell-proliferative (n = 4) responses to the MsIg component of the vaccine. In one patient, a T-cell response specific to autologous Id was also measured. Anti-Id antibodies were not detectable in any patient. A second series of vaccinations was then administered using a needle-free injection device (Biojector) to deliver 1800 micro g both i.m. and intradermally (i.d.); 9 of 12 patients had humoral (n = 6) and/or T-cell (n = 4) responses to MsIg. Six of 12 patients exhibited humoral and/or T-cell anti-Id responses; yet, these were cross-reactive with Id proteins from other patient's tumors. Subsequently, a third series of vaccinations was carried out using 500 micro g of human granulocyte-macrophage colony-stimulating factor DNA mixed with 1800 micro g of Id DNA. The proportion of patients responding to MsIg remained essentially unchanged (8 of 12), although humoral or T-cell responses were boosted in some cases. Throughout the study, no significant side effects or toxicities were observed. Despite the modest level of antitumor immune responses in this study, DNA vaccine technology retains potential advantages in developing anti-Id immunotherapies. Additional studies are warranted to optimize vaccine dose, routes of administration, vector designs, and prime-boost strategies. These results will help guide the design of such future DNA vaccine trials.
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PMID:Immunogenicity of a plasmid DNA vaccine encoding chimeric idiotype in patients with B-cell lymphoma. 1238 47

Interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 5 (IL-5) exert their biological activities through interaction with cell-surface receptors that consist of two subunits, a specific a subunit and a common beta transducing subunit (beta c). We have evaluated the effect of growth factors on the expression of beta c in normal monocytes. Addition of either GM-CSF or M-CSF to monocytes elicited a marked increase of beta c chain expression, a phenomenon seemingly related to a stimulation of the transcriptional activity of this gene mediated through an enhancement of the PU.1 DNA binding activity. Interestingly, during the activation of beta c chain expression by growth factors a switch from the synthesis of the truncated betaIT to the full-length beta c was observed. Similar observations have been made also in the growth factor-dependent erythroleukemic cell line TF-1, showing that GM-CSF deprivation elicited a marked decrease of beta c chain expression.
Leuk Lymphoma 2002 Aug
PMID:Modulation by growth factors of the expression of interleukin 3 and granulocyte-macrophage colony-stimulating factor receptor common chain beta c. 1240 Jun 8

The objective of the study is to explore the effect of Fas, FasL and Bcl-2 on the process of apoptosis induced by chemotherapeutic drugs through detecting the expression of Fas, FasL and Bcl-2 on murine lymphoma cell line RMA. Dexamethasone(DEX), etoposide (VP-16), arsenic trioxide As(2)O(3) and all trans-retinoic-acid (ATRA) were added to the RMA cells as well as to the cells preincubated with interleukin-2 (IL-2), interleukin-6 (IL-6) or granulocyte-macrophage colony-stimulating factor (GM-CSF), respectively. The effect on apoptosis was observed and the expression of Fas and FasL mRNA as well as the expression of Fas and Bcl-2 antigen were measured. DEX and VP-16 could promote apoptosis of RMA cells while upregulating the expression of Fas and FasL without affecting the expression of Bcl-2. ATRA downregulated the expression of Bcl-2 without any change of Fas and FasL, and no apoptosis of RMA cells induced by ATRA was observed. Although As(2)O(3) induced apoptosis of RMA cells, it did not affect the expression of Fas, FasL and Bcl-2, which suggested that different drugs induce apoptosis of the same kind of cells by different signal transduction system and apoptosis induced by Fas system needed the coexistence of Fas and FasL. Although IL-2, IL-6 and GM-CSF upregulated the expression of Fas protein when adding to RMA cells separately, none of them induced apoptosis. Apoptosis could be induced by combination of IL-2 and IL-6 along with the upregulation of Fas and FasL. The cytokines facilitated the apoptotic action of chemotherapeutic drugs, the drug concentration for inducing apoptosis decreased and the time period of starting apoptosis shortened. Apoptosis could be observed without the expression of FasL when anti-Fas-antibody was added to RMA cells. The results demonstrated that there was synergistic effect of chemotherapeutic drugs and some cytokines for induction of apoptosis. Fas-FasL system participated in the apoptosis induced by DEX and VP-16; different drugs induce apoptosis by different pathway of signal transduction.
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PMID:[The expression of Fas, FasL and Bcl-2 on RMA cells during the process of apoptosis induced by chemotherapeutic drugs]. 1251 34

To elucidate the differences in pathogenesis between lymphoma-associated hemophagocytic syndromes (LAHS) of the T-cell/ natural killer cell (T/NK) and B-cell (B) types, we comparatively analyzed the clinical features and serum cytokine profiles of 33 patients with LAHS registered in the Kyoto University Hematology/Oncology Study Group. The serum cytokine levels of each patient group (B-LAHS versus T/NK-LAHS) were expressed as the ratio of the median to the upper normal values of the respective cytokines and were as follows: 19.05 versus 13.99 for soluble interleukin 2 (IL-2) receptor, 0.67 versus 0.67 for granulocyte-macrophage colony-stimulating factor (GM-CSF), 0.64 versus 1.26 for G-CSF, 5.70 versus 3.61 for M-CSF, 1.54 versus 3.39 for interferon gamma (IFN-gamma), 13.17 versus 1.17 for IL-6, 6.88 versus 1.58 for tumor necrosis factor alpha (TNF-alpha), 0.71 versus 0.41 for IL-1beta, 1.99 versus 0.21 for IL-12, and 105.32 versus 29.65 for IL-10. The serum levels of IL-6, TNF-alpha, and IL-10 were significantly higher in the B-LAHS group, whereas those of IFN-y were significantly lower. These differences between the 2 groups may reflect a difference in the pathogenesis Higher serum levels of IL-6, TNF-alpha, and IL-10 may be derived at least partly from neoplastic B-cells themselves In addition, the extremely high serum levels of IL-10 suggest that a compensatory anti-inflammatory process may operate in both groups and give rise to a profound immunosuppressive state and a poor outcome.
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PMID:The serum cytokine profiles of lymphoma-associated hemophagocytic syndrome: a comparative analysis of B-cell and T-cell/natural killer cell lymphomas. 1273 74

This study was designed to evaluate the feasibility, toxicity, and efficacy of rituximab added to the VNCOP-B (etoposide/mitoxantrone/cyclophosphamide/vincristine/prednisone/bleomycin) combination regimen for the treatment of elderly patients with large B-cell lymphoma. Previously untreated patients > or = 65 years of age with stage II, III, or IV large B-cell non-Hodgkin's lymphoma were treated with a modified VNCOP-B regimen with weekly chemotherapy for 8 weeks. In addition, patients received rituximab 375 mg/m2 intravenously on weeks 1, 2, 3, 4, 6, and 8. All patients received prophylactic granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) during the 8 weeks of treatment. Between August 1999 and February 2002, 41 patients entered this multicenter phase II trial. The median age was 74 years, and 54% of patients had high-risk tumors (age-adjusted International Prognostic Index scores of 2 or 3). Sixty-eight percent of patients completed the 8 weeks of therapy. Overall response rate was 66%; actuarial progression-free survival rate at 2 years was 59%, with a 57% actuarial overall 2-year survival rate. Patients > or = 75 years of age had similar treatment outcomes compared with younger patients. Toxicity with this regimen was predominantly related to chemotherapy; rituximab was well tolerated. Grade 3/4 neutropenia occurred in 83% of patients even with routine use of prophylactic G-CSF or GM-CSF. Treatment-related death occurred in 4 patients (10%). VNCOP-B plus rituximab is efficacious, producing 2-year progression-free survival rates that compare favorably with those of other active regimens in this patient group. Hematologic toxicity was increased compared with previous reports with VNCOP-B alone, as evidenced by the treatment-related mortality rate of 10% in the present study. Differences in toxicity may have been caused by the addition of rituximab, the modified etoposide schedule, or the differences in patient characteristics. This regimen provides a treatment option for elderly patients who are not considered candidates for standard CHOP/rituximab chemotherapy.
Clin Lymphoma 2003 Jun
PMID:First-line treatment with brief-duration chemotherapy plus rituximab in elderly patients with intermediate-grade non-Hodgkin's lymphoma: phase II trial. 1283 53

The analysis of chromosomal abnormalities is important for the study of hematological neoplastic disorders since it facilitates classification of the disease. The ability to perform chromosome analysis of cryopreserved malignant marrow or peripheral blast cells is important for retrospective studies. In the present study, we compared the karyotype of fresh bone marrow cells (20 metaphases) to that of cells stored with a simplified cryopreservation method, evaluated the effect of the use of granulocyte-macrophage colony-stimulating factor (GM-CSF) as an in vitro mitotic index stimulator, and compared the cell viability and chromosome morphology of fresh and cryopreserved cells whenever possible (sufficient metaphases for analysis). Twenty-five bone marrow samples from 24 patients with hematological disorders such as acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, chronic myeloid leukemia, megaloblastic anemia and lymphoma (8, 3, 3, 8, 1, and 1 patients, respectively) were selected at diagnosis, at relapse or during routine follow-up and one sample was obtained from a bone marrow donor after informed consent. Average cell viability before and after freezing was 98.8 and 78.5%, respectively (P < 0.05). Cytogenetic analysis was successful in 76% of fresh cell cultures, as opposed to 52% of cryopreserved samples (P < 0.05). GM-CSF had no proliferative effect before or after freezing. The morphological aspects of the chromosomes in fresh and cryopreserved cells were subjectively the same. The present study shows that cytogenetic analysis of cryopreserved bone marrow cells can be a reliable alternative when fresh cell analysis cannot be done, notwithstanding the reduced viability and lower percent of successful analysis that are associated with freezing.
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PMID:Karyotype of cryopreserved bone marrow cells. 1284 70

The granulopoiesis-stimulating factors, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), are used to prevent neutropenia and febrile neutropenia in patients with malignant lymphoma. The question as to whether G-CSF/GM-CSF improves dose-intensity, tumour response and overall survival (OS) has not yet been answered. As the results from single studies are inconclusive, a systematic review was performed to determine the effectiveness of G-CSF/GM-CSF. Randomized controlled trials comparing prophylaxis with G-CSF/GM-CSF versus no prophylaxis in adult patients with malignant lymphoma undergoing conventional chemotherapy were included. Medical databases (Cochrane Library, Medline, Embase) and conference proceedings were searched. All authors were contacted to obtain missing data. We included 11 studies making a total of 1434 patients. Compared with no prophylaxis, G-CSF/GM-CSF significantly reduced the relative risk (RR) for neutropenia [RR 0.64 [95% confidence interval (CI) 0.55-0.75]] febrile neutropenia (RR 0.74 [95% CI 0.62-0.89]) and infection (RR 0.74 [95% CI 0.64-0.85]). G-CSF/GM-CSF did not decrease infection-related mortality (RR 2.07 [95% CI 0.81-5.34]), improve complete remission (CR) (RR 1.06 [95% CI 0.96-1.16]) or OS (HR 0.98 [95% CI 0.81-1.18]). In conclusion, G-CSF/GM-CSF given during conventional chemotherapy in malignant lymphoma patients reduced the RR of neutropenia, febrile neutropenia and infection. However, there is no evidence that G-CSF/GM-CSF improved CR and OS in this clinical setting.
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PMID:Impact of granulocyte colony-stimulating factor (CSF) and granulocyte-macrophage CSF in patients with malignant lymphoma: a systematic review. 1287 68

Both hemophagocytic lymphohistiocytosis and hypereosinophilic syndrome have been associated with hematologic neoplasms and are respectively related to an overproduction of the cytokines Thelper 1 (Th1) and Th2 by tumor cells or reactive cells. To our knowledge, this is the first time a case of a peripheral T-cell lymphoma consecutively associated with both paraneoplastic conditions has been reported. Importantly, in this case when the lymphoma exclusively involved the bone marrow, severe paraneoplastic systemic damage, a CD8+ suppressor/cytotoxic phenotype and a hypereosinophilia not related to high levels of interleukin (IL)-5 was found. Interestingly, progression of the lymphoma coincided with an increase in the serum levels of several Th2 cytokines and IL-2, a decrease in tumor necrosis factor and granulocyte-macrophage colony-stimulating factor levels and the onset of a hypereosinophilic syndrome.
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PMID:Peripheral T-cell lymphoma associated consecutively with hemophagocytic lymphohistiocytosis and hypereosinophilic syndrome. 1295 Feb 42


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