Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A mouse-human chimeric monoclonal antibody (mAb), MH162, against P-glycoprotein was previously found to be more effective than an all-mouse mAb (MRK16) in lysis of multidrug-resistant (MDR) tumor cells by blood mononuclear cells. The present study was performed to identify the effector cells responsible for the chimeric mAb-dependent cell-mediated cytotoxicity (ADCC) against MDR cells. The ADCC reaction was assessed by a 6-h 51Cr release assay. Highly purified lymphocytes (greater than 99%), monocytes (greater than 99%) and neutrophils (greater than 96%) were obtained from peripheral blood of the same healthy donors. A comparison of these three effector cell populations showed no difference between MH162 and its all-murine counterpart MRK16 in MDR cell lysis by monocytes or neutrophils. But MH162 was more effective than MRK16 in lymphocyte-mediated lysis of the MDR cells. The lymphocytes responsible for this ADCC had CD16+ Fc receptors. Pretreatment of monocytes with colony-stimulating factors (IL-3, GM-CSF and M-CSF) caused significant increase in their MH162-mediated lysis of MDR cells. Another anti-P-glycoprotein chimeric mAb (MH171) was also more effective than its murine counterpart MRK17 in lymphocyte-mediated lysis of MDR cells. These findings suggest that mouse-human chimeric mAbs may be useful therapeutically for in vivo destruction of MDR cancer cells by the ADCC reaction.
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PMID:Effector cell analysis of human multidrug-resistant cell killing by mouse-human chimeric antibody against P-glycoprotein. 135 55

GM-CSF represents an important advance in bone marrow transplantation. The drug can be given safely and does not appear to increase the risk of graft-versus-host disease or tumor relapse. This is a rare example of a new technology reducing the cost of health care. By shortening the duration of hospitalization, GM-CSF can significantly reduce the cost of a bone marrow transplant (Table 2). However, there are few data to support the conclusion that the reduction in the duration of neutropenia is associated with a superior survival. This attests to the excellent supportive care that has been developed for patients undergoing bone marrow transplantation. At present, GM-CSF has become a standard therapy in autologous bone marrow transplantation. However, the future will undoubtedly see the development of combinations of hematopoietic growth factors and/or new growth factors that will further improve our ability to perform bone marrow transplantation.
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PMID:The use of granulocyte-macrophage colony-stimulating factor in bone marrow transplantation. 136 21

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered intraperitoneally in combination with multidrug chemotherapy using methotrexate (M), vinblastine (V), doxorubicin (A), and cisplatin (C, or for the combination, MVAC) to C3H/He mice (5-week-old females) after experimental carcinoma, MBT-2, a transplantable transitional cell carcinoma of the urinary bladder had been implanted. The effects of therapy were studied. The animal groups consisted of: (1) control (no drug administration), (2) rhG-CSF (100 micrograms/kg/d, from days 8 through 42 after MBT-2 implantation, except for the days when MVAC was administered), (3) high-dose MVAC (2 mg/kg of M, 0.2 mg/kg of V, 2 mg/kg of A, and 4 mg/kg of C once a week for 3 weeks), (4) low-dose MVAC (one-quarter of the high dose), (5) high-dose MVAC with rhG-CSF, and (6) low-dose MVAC with rhG-CSF. In an in vitro system, rhG-CSF did not show any effect on the proliferation of MBT-2 cells or exert any influences on A's tumor proliferation-suppressing action on MBT-2. However, in an in vivo system, concomitant administration of rhG-CSF significantly enhanced the tumor-suppressing effect of the MVAC therapy, as did rhG-CSF alone. The greatest effect was observed in the group receiving high-dose MVAC plus rhG-CSF. These result suggested that rhG-CSF-stimulated granulocytes may exert antitumor activity on tumor cells severely damaged by chemotherapeutic agents at a relatively high concentration. The survival rate was improved to some degree even by administration of rhG-CSF alone. Although further study is required to elucidate the action mechanism of rhG-CSF, these results suggest that rhG-CSF may be useful clinically to enhance the activity of antitumor agents and not only through its ability to alleviate granulocytopenia or prevent its development.
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PMID:Enhancement of chemotherapeutic effects by recombinant human granulocyte colony-stimulating factor on implanted mouse bladder cancer cells (MBT-2). 137 Sep 20

We have examined the effect of the macrocyclic lactone protein kinase C (PK-C) activator bryostatin 1 on the in vitro radioprotective capacity of recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) toward normal committed myeloid progenitor cells (day-14 granulocyte-macrophage colony-forming units [CFU-GM]). Preincubation of T-cell- and adherent cell-depleted bone marrow mononuclear cells with 12.5 nM bryostatin 1 and either 1.25 or 50 ng/ml rGM-CSF for 24 h resulted in an 18%-30% survival at 4-5 Gy, whereas cells exposed to rGM-CSF alone gave rise to no detectable colonies at radiation doses greater than 2.5 Gy. Coadministration of bryostatin 1 also led to a threefold increase in Do values for both rGM-CSF concentrations. A similar enhancement of radioprotective effects was observed with the tumor-promoting phorbol ester phorbol dibutyrate. Exposure of cells to both bryostatin 1 and rGM-CSF immediately following irradiation also resulted in enhanced progenitor cell survival when compared to rGM-CSF alone, but radioprotective effects were less than those observed when cells were preincubated with these factors. Cells preconditioned with bryostatin 1 and rGM-CSF prior to exposure to 2 or 4 Gy gave rise to significantly more colonies when radiation was administered as a 4-h divided dose, suggesting that bryostatin 1 may act by potentiating rGM-CSF-induced repair of sublethal radiation damage. Finally, pre-exposure of enriched progenitor cells (CD34+) to bryostatin 1 and rGM-CSF resulted in radioprotective effects that were less than those observed for partially purified populations with respect to the total population of surviving myeloid colonies. However, CD34+ cells preincubated with bryostatin 1 and rGM-CSF prior to irradiation exhibited a significant increase in both the percentage and absolute number of neutrophilic and macrophage colonies, and a reduction in eosinophilic colonies, compared to cells exposed to rGM-CSF alone. These studies suggest that bryostatin 1 (and possibly other PK-C activators) potentiates the in vitro radioprotective effects of rGM-CSF and may also regulate the lineage specificity of this response.
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PMID:Effect of bryostatin 1 on the in vitro radioprotective capacity of recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) toward committed human myeloid progenitor cells (CFU-GM). 137 43

To evaluate the clinical effect by administration of recombinant human granulocyte-stimulating factor (rhG-CSF) post chemotherapy in non-Hodgkin malignant lymphoma (NHL), 17 patients with NHL were subjected to this study. Administration of rhG-CSF ameliorated the decrease in absolute neutrophil counts after the cytotoxic chemotherapies and activated neutrophil functions in active oxygen product and expressions of adhesion proteins. To consistent with these results, rhG-CSF administrations post cytotoxic chemotherapy were effective for reducing infection complications associated with neutropenia. Furthermore, administration of rhG-CSF increased peripheral hematopoietic progenitor cells, thus suggesting promising therapeutic potential for autografting. Recently, it has been reported that blood neutrophils may synthesize mRNA and proteins important in inflammation including various cytokines such as IL-1, IL-6, TNF-alpha and IFN-alpha, but, administration of rhG-CSF showed no obvious effect on the level of either IL-1, IL-6, TNF-alpha or IFN-alpha in sera, and furthermore, the in vitro stimulation by rhG-CSF induced no significant production of these cytokines and expressions of TNF-alpha and IFN-alpha mRNAs. Finally, we studied on anti-tumor effect of administration of rhG-CSF in CDF1 mice inoculated with syngeneic lymphoma cells. rhG-CSF infusion suppressed the liver metastasis and prolonged the overall survival, thus suggesting the hypothesis that use of rhG-CSF in some patients with NHL might control the disease through stimulating both production and functional activation of neutrophils.
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PMID:[In vivo effects on human neutrophils by administration of rhG-CSF and clinical significance]. 137 67

We have previously demonstrated that the murine colon adenocarcinoma C-26 cell line transduced with the human gene for the granulocyte CSF (G-CSF) loses tumorigenic activity through a mechanism that involved massive targeting of neutrophils at the site of tumor injection. The suppression of tumorigenicity by G-CSF was limited to the G-CSF-producing cells and was not transferred to nonproducing C-26 cells in a mixed tumor transplantation assay. We present direct evidence that neutrophils are involved in this phenomenon. We firstly examined, by electron microscopy (EM), the morphology of tumor infiltrates obtained 2, 5, and 10 days after s.c. injection of a mixture of G-CSF-producing and -nonproducing C-26 cells into syngeneic BALB/c mice. The EM analysis showed at 5, but not at 2 or 10 days, the presence of neutrophils in intimate contact with tumor cells. We then investigated whether neutrophils discriminate between G-CSF-producing and -nonproducing C-26 cells. To this aim, C-26 cells were transduced, via retroviral vector, with the Escherichia coli LacZ gene and mixed tumor transplantation assays were performed by injecting a mixture of G-CSF-producing beta-gal- and G-CSF-nonproducing beta-gal+ C-26 cells at different ratios. Histologic and EM analysis of the tumors growing at the site of injection were carried out. Five days after injection, treatment with x-gal revealed, at the histochemical level, the presence of neutrophils around G-CSF producing beta-gal- cells; cell-cell contacts and fusion of cell membranes were detected by EM only between neutrophils and G-CSF-producing cells. In vitro experiments, performed in Boyden chambers, confirmed that the G-CSF produced by C-26 cells was a chemoattractant for neutrophils. In addition, a colorimetric, cytostatic assay revealed that neutrophils were able to inhibit the growth of G-CSF-producing but not of G-CSF-nonproducing C-26 cells. Thus the tumor take after injection of G-CSF-producing C-26 cells seems to be controlled in situ through two major mechanisms namely neutrophil chemotaxis and neutrophil-mediated tumor inhibition. The results indicate that neutrophils can discriminate between G-CSF-producing and -nonproducing tumor cells and that neutrophils infiltrate the tumor mixture as long as G-CSF-producing cells are present.
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PMID:Granulocyte colony-stimulating factor (G-CSF) gene transduction in murine adenocarcinoma drives neutrophil-mediated tumor inhibition in vivo. Neutrophils discriminate between G-CSF-producing and G-CSF-nonproducing tumor cells. 137 45

Expression of granulocyte (G) and granulocyte-macrophage (GM) colony stimulating factor (CSF) genes in human cells of astroglial lineage was studied. Primers for CSFs were used to analyze RNA transcripts in 5 cultured human astrocytoma cell lines and 8 fresh brain specimens by polymerase chain reaction. Constitutive expression of mRNA transcripts of GM-CSF could be detected in all astrocytoma and one neuroblastoma cell lines, and two out of 5 unstimulated astrocytomas, U87MG and U138 MG, expressed G-CSF genes. After stimulation with interleukin (IL)-1 beta + tumor necrosis factor (TNF)-alpha, all cell lines expressed G-CSF. In addition to the cultured cells, we examined gene expression within human malignant astrocytoma, peritumoral brain and autopsied normal brains. The results show that some of the tumor and its surrounding reactive lesions express G- and GM-CSF genes but normal brains do not. The concentration of G- and GM-CSF in supernatants of cultured cells was assessed at the protein level by ELISA. A low level of GM-CSF activity was constitutively present in all astrocytomas. G-CSF was detected in unstimulated U87MG and U138MG and other cell lines could synthesize G-CSF after the stimulation of IL-1 beta and TNF-alpha at the level of mRNA. Furthermore, the concentration of CSFs increased markedly upon stimulation with IL-1 beta and/or TNF-alpha in both a time- and dose-dependent fashion. From these results, it is suspected that astroglial cell-derived CSFs may participate in local immune reactions accompanying infection, degeneration and malignancies in the brain.
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PMID:Expression of granulocyte colony stimulating factor and granulocyte-macrophage colony stimulating factor genes in human astrocytoma cell lines and in glioma specimens. 137 84

The present study was designed to evaluate the effects of a recombinant human G-CSF (rhG-CSF) and a mutein G-CSF (KW-2228) on leucopenia and tumor growth in mice treated with 5-fluorouracil (5-FU). In normal mice, the number of leucocytes (white blood cell, WBC) reached the peak 12 hours after a single injection of either type of G-CSF and decreased to the normal level after 24 hours. Daily administration induced a continuous increase in the WBC count, however, administrations at intervals did not. Meth-A fibrosarcoma was subcutaneously inoculated into the backs of syngeneic BALB/c mice. The mice were treated with 5-FU alone or with G-CSFs. Chemotherapy with 5-FU alone resulted in leucopenia and an insignificant inhibition of tumor growth. The conjunctive administration of G-CSFs with 5-FU resulted in a significantly augmented inhibition of tumour growth, and leukopenia was not seen. This augmenting effect was more prominent with KW-2228. These results suggest that in 5-FU chemotherapy G-CSFs may be beneficial in restoring the number of leucocytes from leucopenic state and in augmenting the tumor inhibitory effect. Furthermore, KW-2228 may be more beneficial than the natural type rhG-CSF.
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PMID:Comparative effects of a recombinant and a mutein type of granulocyte colony stimulating factor on the growth of Meth-A fibrosarcoma with 5-fluorouracil chemotherapy. 137 28

Ru 41.740 (Biostim) is an immunostimulating drug of microbial origin which may stimulate human mononuclear blood cells (mainly monocytes) to release soluble factors which inhibit replication of several tumor cell lines in vitro. Since this effect may be of clinical importance in the treatment of cancer a number of tests have been conducted in order to find methods to augment this secretion. In vitro tests suggested that this non-specific antitumor activity of Biostim may not be enhanced by concomitant treatment of patients with inhibitors of cyclo-oxygenase and lipoxygenases or by interferons alpha, beta, gamma or the hemopoietic growth factors GM-CSF and G-CSF.
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PMID:Ru 41.740 triggers human mononuclear blood cells to release tumor growth inhibitory factors in vitro. 137 44

We have reported that polymorphonuclear leukocytes (PMN) and active oxygen species from PMN may play an important role in the mechanism of the antitumor effect of hyperthermia. At this time, we focused our experimental studies on rat AH109A carcinoma treated with hyperthermia combined with arterial injection of rhG-CSF. Rats with transplantable AH109A carcinoma at the hind leg received hyperthermia. These tumors showed mild suppression of further development only by hyperthermia. However, when arterial injection of rhG-CSF was applied together with hyperthermia, marked suppression of tumor development was observed. Our data suggest that hyperthermia combined with rhG-CSF is closely related to the generation of free radical-mediated tumor cell killing, and it can be an effective treatment for cancer.
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PMID:[Role of polymorphonuclear leukocytes (PMN) and active oxygen species in hyperthermia--antitumor effect of hyperthermia combined with rhG-CSF]. 138 99


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