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1.
L. Yuan Masanobu Kobayashi Yasuhiro Kuramitsu Yongging Li Kazushiro Matsushita M. Hosokawa 《Cancer immunology, immunotherapy : CII》1997,45(2):71-76
To explore the mechanisms of immuno-modulatory activities of bleomycin, we investigated interferon γ (IFNγ) mRNA expression,
tumor necrosis factor α (TNFα) production, nitric oxide (NO) production and macrophage tumoricidal activities in rats bearing
KDH-8 hepatoma cells, which secreted a large amount of transforming growth factor β (TGFβ), and these processes in KDH-8 tumor-bearing
rats treated with bleomycin. We found that IFNγ mRNA expression, TNFα production, NO production and macrophage cytotoxic activities
were lower in the KDH-8-bearing rats than in normal rats. On the other hand, low-dose bleomycin restored the macrophage cytotoxic
activities, NO production, IFNγ mRNA expression and TNFα production in the KDH-8-bearing rats. In vitro experiments showed
that KDH-8-derived TGFβ decreased the IFNγ mRNA expression and TNFα production in splenocytes, and NO production in peritoneal
macrophages. These results suggest that low-dose bleomycin restored the cytokine production and macrophage tumoricidal activities
in the KDH-8-bearing rats by decreasing KDH-8-derived TGFβ.
Received: 14 October 1996 / Accepted: 22 July 1997 相似文献
2.
Marion-Gabriele Ott Daniela N. Männel Harald Gallati Matthias Goerig Ulrich Raeth 《Cancer immunology, immunotherapy : CII》1996,42(1):31-37
Tumor necrosis factor α (TNFα) and interferon γ (IFNγ) are important immunomodulators. They are capable of acting in a synergistic
manner on tumor cells in vitro and in vivo. In a clinical phase I study 13 patients with malignant ascites due to abdominal
spread of different primary tumors received intraperitoneally (i. p.) TNFα and IFNγ once weekly over 3 – 8 weeks in order
to evaluate the effect of locoregionally administered TNFα/IFNγ on ascites formation. Therefore some peripheral and local
immunological functional parameters of peripheral blood and malignant ascites were investigated. Mononuclear lymphocytes and
natural killer (NK) cell activity of peripheral blood and ascites, TNF-inhibitory activity, soluble p55 and p75 TNF receptors,
and prostaglandin E2 values in ascites were measured immediately before and 24 h after each TNFα/IFNγ infusion. Peripheral mononuclear lymphocytes
and NK activity decreased significantly 24 h after i. p. TNFα/IFNγ application. However, over the entire treatment schedule,
peripheral NK activity in all responders showed a continuous increase, when compared to pre TNFα/IFNγ treatment levels. In
contrast, NK activity in non-responders constantly decreased. In contrast to non-responders, TNF-inhibitory activity and soluble
p55 TNF receptor levels, determined in ascites, decreased in responders. Taken together, our findings suggest, that successful
locoregional i. p. TNFα/IFNγ therapy induces systemic immunological reactions possibly after saturation of soluble p55 TNF
receptors in ascites, which leads to an increase of peripheral NK activity.
Received: 28 September 1995 / Accepted: 16 November 1995 相似文献
3.
Hasem Habelhah Futoshi Okada Kazumoto Nakai Sung Ki Choi Jun-ichi Hamada Masanobu Kobayashi M. Hosokawa 《Cancer immunology, immunotherapy : CII》1998,46(6):338-344
Previously we reported the malignant progression of QR-32, a regressor-type tumor clone, following co-implantation with foreign
bodies (gelatin sponge or plastic plate) in normal syngeneic C57BL/6 mice. We also reported that the progression of QR-32
cells by a gelatin sponge was significantly inhibited in the mice administered polysaccharide K (PSK) and that PSK induced
an increase of radical scavengers, especially manganese superoxide dismutase (Mn-SOD), locally at the site of tumor tissues.
In this study, to reveal the possible mechanism by which PSK induced Mn-SOD in the tumor tissues, we examined the mRNA expression
and protein levels of inflammatory cytokines in the tissues. We found that mRNAs of tumor necrosis factor α (TNFα) and interleukin-1α
(IL-1α) were considerably expressed in both PSK-treated and phosphate-buffered-saline-treated tumors, and that the mRNA expression
and protein level of interferon γ (IFNγ) increased in the tumor tissues treated with PSK. In vitro treatment of QR-32 cells
with IFNγ did not significantly increase the production of Mn-SOD; however, the combination of IFNγ with TNFα increased the
Mn-SOD production more effectively than did any of the cytokines used singly. Furthermore, we observed the down-regulation
of the mRNA expression and protein level of transforming growth factor β (TGFβ) in the tumor tissues treated with PSK, and
that in vitro treatment of QR-32 cells with TGFβ decreased the production of Mn-SOD. These results suggest that PSK suppresses
the progression of QR-32 cells by increasing Mn-SOD via the modulation of inflammatory cytokines; that is, by decreasing TGF-β
and increasing IFN-γ.
Received: 7 October 1997 / Accepted: 31 March 1998 相似文献
4.
Lixia Chen Guoqing Tian Changxia Shao Everardo Cobos Weimin Gao 《Molecular biology reports》2010,37(7):3105-3110
Curcumin, a polyphenolic compound, is the active component of Curcuma longa and has been extensively investigated as an anticancer drug that modulates multiple pathways. Eukaryotic initiation factors
(eIFs) have been known to play important roles in translation initiation, which controls cell growth and proliferation. Little
is known about the effects of curcumin on eIFs in lung cancer. The objective of this study was to exam the curcumin cytotoxic
effect and modulation of two major rate-limiting translation initiation factors, including eIF2α and eIF4E protein expression
levels in lung adenocarcinoma epithelial cell line A549. Cytotoxicity was measured by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide) assay and protein changes were determined by Western blot. A549 cells were treated with 0–240 μM curcumin for 4–96 h.
The inhibitory effects of curcumin on cytotoxicity were dose- and time-dependent (P < 0.001). The 50% inhibitory curcumin concentrations (IC50s) at 24, 48, 72, and 96 h were 93, 65, 40, and 24 μM, respectively.
Protein expressions of eIF2α, eIF4E, Phospho-4E-BP1 were down-regulated, while Phospho-eIF2α and Phospho-eIF4E were up-regulated
after A549 cells were treated with 20 and 40 μM curcumin for 24 h. In addition, the effects of curcumin on these protein expression
changes followed a significant dose-response (P < 0.05, trend test). These findings suggest that curcumin could reduce cell viability through prohibiting the initiation
of protein synthesis by modulating eIF2α and eIF4E. 相似文献
5.
To avoid destruction by complement, normal and malignant cells express membrane glycoproteins that restrict complement activity.
These include decay-accelerating factor (DAF, CD55), membrane cofactor protein (MCP, CD46) and protectin (CD59), which are
all expressed on colonic adenocarcinoma cells in situ. In this study we have characterised the C3/C5 convertase regulators
DAF and MCP on the human colonic adenocarcinoma cell line HT29. DAF was found to be a glycosyl-phosphatidylinositol-anchored
70-kDa glycoprotein. Blocking experiments with F(ab′)2 fragments of the anti-DAF monoclonal antibody BRIC 216 showed that DAF modulates the degree of C3 deposition and mediates
resistance to complement-mediated killing of the cells. The expression and function of DAF were enhanced by tumour necrosis
factor α (TNFα) and interleukin-1β (IL-1β). Cells incubated with interferon γ (IFNγ) did not alter their DAF expression. Two
MCP forms were expressed, with molecular masses of approximately 58 kDa and 68 kDa, the lower form predominating. MCP expression
was up-regulated by IL-1β, but not by TNFα or IFNγ. Expression of DAF and MCP promotes resistance of colonic adenocarcinoma
cells to complement-mediated damage, and represents a possible mechanism of tumour escape.
Received: 18 July 1995 / Accepted: 4 January 1996 相似文献
6.
G. R. Newton D. W. Weise J. A. Bowen S. Woldesenbet R. C. Burghardt 《In vitro cellular & developmental biology. Animal》1998,34(7):578-584
Summary Caprine uterine epithelial (UE) cells were cultured on Matrigel-coated filters. Transmission electron microscopy revealed
polarized UE cells characterized by basally located nuclei, apical microvilli, convoluted lateral membranes, and junctional
complexes. Domain-specific secretion of prostaglandins and radiolabeled proteins provide further evidence of functional epithelial
cell polarity. Two experiments were conducted to evaluate factors controlling prostaglandin E2 (PGE) and prostaglandin F2α (PGF) secretion. In experiment one, steroid-treated (estradiol, progesterone, or estradiol + progesterone) polarized UE cells
were treated with interferon tau (IFNτ) and/or oxytocin (OT). Steroid treatment did not influence PGE or PGF secretion. However,
analysis of variance revealed an IFNτ by OT interaction (P<.01) for both PGE and PGF. This interaction was caused by a reduction in PGE and PGF secretion by cultures receiving only
IFNτ and the inability of IFNτ to block OT-induced release of PGE or PGF. In experiment 2, polarized UE cells were cultured
in progesterone, with or without IFNτ, and sequentially challenged with estradiol and OT. Oxytocin stimulated the release
of both PGE and PGF by polarized cUE cells (P<.01) and resulted in an increased accumulation of PGE (OT*domain; P<.01) in the basal compartment. Interferon tau did not influence PGE (P<.1) secretion. However, further analysis revealed that IFNτ reduced PGF secretion and was unable to block OT-induced PGF
secretion (IFNτ*OT; P<.05) by polarized UE cells. Therefore, caprine UE cells form polarized monolayers and retain responsiveness to IFNτ and OT
in vitro. 相似文献
7.
8.
Brady MS Lee F Petrie H Eckels DD Lee JS 《Cancer immunology, immunotherapy : CII》2000,48(11):621-626
Purpose: Most melanoma cell lines express HLA class II antigens constitutively or can be induced to do so with interferon γ (IFNγ).
We have previously demonstrated that peptide-specific CD4+ T cells proliferate in response to HLA-class-II-antigen-mediated peptide presentation by melanoma cells in vitro and produce
interleukin-10 (IL-10) and (IFNγ). We asked whether the responding T cells kill the tumor cells and, if so, whether direct
cell contact was required. Methods: Two HLA class II+ melanoma cell lines derived from metastases were co-cultured with a human CD4+ T cell clone specific for influenza hemagglutinin peptide (HA). T cells, melanoma, and HA were co-cultured for 48 h. Melanoma
cells with and without HA and/or T cells served as controls. After 36 h, the medium was removed for cytokine analysis by enzyme-linked
immunosorbent assay (ELISA). Twelve hours later non-adherent cells were washed away and the adherent melanoma cells were trypsinized
and counted. Dual-chamber culture plates were used to determine whether cell contact and/or exposure to cytokine were required
for tumor cell death. Results: Melanoma cell counts were over 80% lower in wells containing T cells than in wells with melanoma and peptide alone (P < 0.05). ELISA of supernatants revealed production of IFNγ and IL-10 by the responding T cells. Direct T cell contact with
tumor cells was not required for tumor cell death, as melanoma cells were killed when they shared medium but had no contact
with T cells responding to peptide presentation by HLA-class-II-antigen-positive melanoma cells in a separate chamber. Blocking
antibody to IFNγ but not IL-10 prevented melanoma cell death at levels of cytokine similar to that present in co-culture assays.
Conclusions: Peptide-specific CD4+ T cells kill melanoma cells in vitro when they recognize peptide presented by the tumor cell in the context of HLA class
II antigen. Direct cell contact is not required, suggesting that it is a cytokine-mediated event. Immunotherapy, using primed
CD4+ T cells and peptide, may be beneficial in patients whose tumors express HLA class II antigens or can be induced to do so
with IFNγ.
Received: 1 July 1999 / Accepted: 17 September 1999 相似文献
9.
10.
Masato Okamoto Ryoji Kaji Hisashi Goda Go Ohe Hideo Yoshida Mitsunobu Sato Hirofumi Kasatani 《Cancer immunology, immunotherapy : CII》1998,47(4):233-241
It has been reported that certain chemotherapeutic agents exhibit effects that enhance the antitumor host responses in the
patients with malignant diseases. In the present study, we investigated whether cis-diamminedichloroplatinum (cisplatin) and 5-fluorouracil (5-FU) may induce cytokines and effector cells with antitumor efficacy
in vivo and in vitro. The cultivation of human peripheral blood mononuclear cells (PBMC) in the presence of cisplatin (0–1.0
μg/ml) or 5-FU (0–5.0 μg/ml) resulted in the significant augmentation of natural killer (NK) and lymphokine-activated killer
(LAK) cell activities as well as generation of interferon (IFN) γ, tumor necrosis factor (TNF) α, β, interleukin(IL)-1β, IL-6
and IL-12 in vitro. In addition, all of these activities were almost completely neutralized by addition of anti-asialoGM1
antibody and complement (P < 0.05). In an in vivo model, the administration of anti-asialoGM1 antibody significantly shortened the survival time extended
by the treatment with cisplatin or 5-FU (P < 0.05), both on nude mice bearing salivary gland tumors and on syngeneic MethA-tumor-bearing BALB/c mice. Furthermore, high
levels of NK and LAK activities and significant increases of the numbers of cells positive for asialoGM1, IFNγ, TNFα, or IL-1β
were detected in the spleen cells derived from animals given cisplatin or 5-FU as compared with those given saline (P < 0.001–0.05). These findings clearly indicate that cisplatin and 5-FU are potent inducers of several types of cytokines and
effector cells carrying antitumor activity mediated by asialoGM1-positive cells (mainly NK cells) for the most part, and that
these abilities are closely associated with the in vivo antitumor effect of these agents.
Received: 23 July 1998 / Accepted: 10 September 1998 相似文献
11.
Pérez E García-Martínez O Arroyo-Morales M Reyes-Botella C Ruiz C 《Bioscience reports》2006,26(4):281-289
Background/Aims Recent reports demonstrated that osteoblast-like cells can also exert activities directly associated with the immune system (cytokine synthesis, antigen presentation, phagocytosis and stimulation of T lymphocytes). The present study aimed to analyze the effect of Transforming growth factorβ1 (TGFβ1), Fibroblast growth factor basic (FGFb), Platelet-derived growth factor-BB (PDGF-BB), Interleukin-1β (IL-1β), Interleukin-2 (IL-2), Lipopolysaccharide (LPS) and Interferon-γ (IFNγ) on the expression on osteoblast-like cells of antigens involved in antigen presentation.Methods Flow cytometry was used to investigate whether the growth factors FGFb, TGFβ1, PDGF-BB, IL-2, IL-1β, LPS and IFNγ modulate the expression on cultured human osteoblast-like cells of different antigens involved in antigen-presentation and T cell activation.Results TGFβ1 treatment significantly reduced the expression of CD54 and CD86. IL-1β treatment significantly enhanced the expression of CD54, CD86 and HLA-DR. LPS and IFNγ treatments produced a major increase in CD54, CD80, CD86 and HLA-DR expression. Expression of these antigen-presenting molecules was not significantly modified by FGFb, PDGF-BB or IL-2 treatment. 相似文献
12.
Type 1 diabetes (T1D) results from autoimmune destruction of the insulin-producing β-cells in the pancreatic islets of Langerhans
by autoreactive T helper 1 (Th1) cells characterized by their cytokine secretory products, interleukin-2 (IL-2) and interferon
γ (IFNγ). Th1-type cytokines (IL-2 and IFNγ) correlate with T1D, whereas Th2 (IL-4 and IL-10), Th3 (transforming growth factor
beta [TGFβ]), and T regulatory cell-type cytokines (IL-10 and TGFβ) correlate with protection from T1D. Paradoxically, however,
administrations of Th1-type cytokines (IL-2 and IFNγ) and immunotherapies that induce Th1-type cytokine responses actually
prevent T1D, at least in animal models. Therefore, immunotherapies that inhibit IL-2 production/action will block Th1 cell/cytokine-driven
effector mechanisms of pancreatic islet β-cell destruction; however, anti-IL-2 therapy will not allow immune tolerance to
be established. In contrast, immunotherapies that increase IL-2 production/action may correct an immunodeficiency in IL-2
production that appears to underlie the autoimmunity of T1D, thereby restoring immune tolerance to islet β-cells and prevention
of T1D. 相似文献
13.
The inability of certain neoplastic populations to undergo Fas-mediated death by immune effector mechanisms may confer a
selective survival advantage, which may contribute to tumor escape. In this study, we examined the role of Fas-mediated lysis
in a human-antigen (Ag)-specific cytotoxic T lymphocyte (CTL)/colon carcinoma cell model, and the regulation of the lytic
phenotype by interferon γ (IFNγ). Previously, we have identified mutated ras peptides reflecting the valine-for-glycine substitution at position 12 as unique HLA-A2-restricted, CD8+ CTL neo-epitopes. Peptide-specific CTL, established from both normal and carcinoma-bearing individuals, lysed in vitro a
HLA-A2+ primary colon adenocarcinoma cell line, SW480, harboring the naturally occurring ras mutation. Pretreatment of SW480 cells with IFNγ was necessary to promote efficient Ag-specific CTL killing, although the
mechanisms by which IFNγ influenced the lytic outcome remains to be elucidated. Here, we show, by phenotypic analysis of SW480
cells, a significant up-regulation of HLA-A2, ICAM-1 and Fas molecules after IFNγ pretreatment, which paralleled their sensitivity
to lysis with anti-Fas stimuli. Moreover, nearly half of the lytic response to IFNγ-treated SW480 cells was inhibited by neutralizing
anti-Fas or anti-Fasligand (FasL) mAb, revealing for the first time an important functional role for Fas/FasL interactions
in carcinoma cell killing by human Ag-specific CTL. mAb against HLA-A2, ICAM-1, the αβ T cell receptor (TCR) and Fas molecules
inhibited lysis; however, if these CTL were preactivated to express functional FasL and then used as effectors, only anti-Fas
mAb efficiently blocked lysis. IFNγ also increased pro-caspase-3 protein expression and its subsequent activation in SW480
cells following Ag-specific CTL attack. Peptide-based caspase inhibitors blocked both caspase-3 activation and CTL-mediated
lysis. Overall, these data suggested that IFNγ (a) facilitated both Ag-dependent and Ag-independent events as a prerequisite
for efficient CTL/target interactions, FasL up-regulation and triggering of Fas-dependent, as well as Fas-independent lysis
(perforin); and (b) enhanced or restored a Fas-sensitive phenotype in SW480 cells, reflecting modulation of cell-surface and
intracellular elements of the Fas pathway. Thus, IFNγ may play an important role in the regulation of a human neoplastic cell
death phenotype, which may have implications for our understanding of the processes of both tumor evasion and tumor regression
following Ag-specific CTL attack.
Received: 20 December 1999 / Accepted: 1 February 2000 相似文献
14.
Miki Watanabe Sulaiman Sheriff Theresa A. Ramelot Nijiati Kadeer Junho Cho Kenneth B. Lewis Ambikaipakan Balasubramaniam Michael A. Kennedy 《International journal of peptide research and therapeutics》2011,17(4):281-299
After severe burn injury, proinflammatory cytokine levels are elevated in serum and skeletal muscle, which in turn increases
protein breakdown and decreases protein synthesis. In this study, C2C12 mouse skeletal muscle cell line myotubes were exposed
to proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) as an in vitro cell-line model of catabolic
response to burn injury and then treated with des-acyl ghrelin (DAG), a 28 amino acid polypeptide hormone thought to inhibit
protein breakdown and increase protein synthesis, to assess its therapeutic potential. Nuclear magnetic resonance-based metabonomics
was used to monitor metabolic activity of C2C12 myotubes under four treatment conditions: (1) control, (2) TNF-α/IFN-γ (TI),
(3) DAG (DA), and (4) TNF-α/IFN-γ followed by DAG (TIDA) to assess the effect of DAG treatment on cellular metabolic response
during basal or catabolic conditions. Twelve metabolites showed significant changes in concentrations following treatments
in the hydrophilic cell extracts. Lactate (P < 10−4) and citrulline (P < 10−9) increased with TNF-α/IFN-γ treatment, indicating increased protein degradation, and returned to control levels in the TIDA
group. Adenosine nucleotide levels had decreased trends in TI myotubes that returned to baseline levels after DAG treatment
(P < 10−4). Guanidinoacetate and pantothenate, metabolites involved in protein synthesis and cell proliferation, had increased concentration
trends following DAG treatment in both the DA and TIDA groups. Our metabonomics analysis provides further evidence that DAG
counteracts the catabolic response caused by elevated muscle TNF-α/IFN-γ cytokine levels following severe burns and can play
a potential therapeutic role in treatment of burn injury. 相似文献
15.
PA28 subunits of the mouse proteasome: primary structures and chromosomal localization of the genes 总被引:2,自引:0,他引:2
The 20S proteasome is a multi-subunit protease responsible for the production of peptides presented by major histocompatibility
complex (MHC) class I molecules. Recent evidence indicates that an interferon-γ (IFN-γ)-inducible PA28 activator complex enhances
the generation of class I binding peptides by altering the cleavage pattern of the proteasome. In the present study, we determined
the primary structures of the mouse PA28 α- and β-subunits. The deduced amino acid sequences of the α- and β-subunits were
49% identical. We also determined the primary structure of the mouse PA28 γ-subunit (Ki antigen), a protein of unknown function
structurally related to the α- and β-subunits. The amino acid sequence identity of the γ-subunit to the α- and β-subunits
was 40% and 32%, respectively. Interspecific backcross mapping showed that the mouse genes coding for the α- and β-subunits
(designated Psme1 and Psme2, respectively) are tightly linked and map close to the Atp5g1 locus on chromosome 14. Thus, unlike the LMP2 and LMP7 subunits, the IFN-γ-inducible subunits of PA28 are encoded outside
the MHC. The gene coding for the γ-subunit (designated Psme3) was mapped to the vicinity of the Brca1 locus on chromosome 11. A computer search of the DNA databases identified a γ-subunit-like protein in ticks and Caenorhabditis elegans, the organisms with no adaptive immune system. It appears that the IFN-γ-inducible α- and β-subunits emerged by gene duplication
from a γ-subunit-like precursor.
Received: 11 March 1997 相似文献
16.
The microvasculature of the corpus luteum (CL), which comprises greater than 50% of the total number of cells in the CL, is
thought to be the first structure to undergo degeneration via apoptosis during luteolysis. These studies compared the apoptotic
potential of various cytokines (tumor necrosis factor α, TNFα; interferon gamma, IFNγ; soluble Fas ligand, sFasL), a FAS activating
antibody (FasAb), and the luteolytic hormone prostaglandin F2α (PGF2α) on CL-derived endothelial (CLENDO) cells. Neither sFasL, FasAb nor PGF2α had any effect on CLENDO cell viability. Utilizing morphological and biochemical parameters it was evident that TNFα and
IFNγ initiated apoptosis in long-term cultures. However, TNFα was the most potent stimulus for CLENDO cell apoptosis at early
time points. Unlike many other studies described in non-reproductive cell types, TNFα induced apoptosis of CLENDO cells occurs
in the absence of inhibitors of protein synthesis. TNFα-induced death is typically associated with acute activation of distinct
intracellular signaling pathways (e.g. MAPK and sphingomyelin pathways). Treatment with TNFα for 5–30 min activated MAPKs (ERK, p38, and JNK), and increased ceramide
accumulation. Ceramide, a product of sphingomyelin hydrolysis, can serve as an upstream activator of members of the MAPK family
independently in numerous cell types, and is a well-established pro-apoptotic second messenger. Like TNFα, treatment of CLENDO
cells with exogenous ceramide significantly induced endothelial apoptosis. Ceramide also activated the JNK pathway, but had
no effect on ERK and p38 MAPKs. Pretreatment of CLENDO cells with glutathione (GSH), an intracellular reducing agent and known
inhibitor of reactive oxygen species (ROS) or TNFα-induced apoptosis, significantly attenuated TNFα-induced apoptosis. It
is hypothesized that TNFα kills CLENDO cells through elevation of reactive oxygen species, and intracellular signals that
promote apoptosis. 相似文献
17.
Mitsuhiro Takenoyama Kosei Yasumoto Mamoru Harada Keizo Sugimachi Kikuo Nomoto 《Cancer immunology, immunotherapy : CII》1998,47(4):213-220
Monoclonal antibodies (mAb) are promising substances for the treatment of colorectal carcinoma, but the efficiency of this
therapy still needs further improvement. We used a flow-cytometric cytotoxicity test to determine the efficacy of the cytokines
interferon α (IFNα) and γ (IFNγ), interleukin-2 (IL-2), macrophage-colony-stimulating factor (M-CSF), granulocyte/macrophage-CSF
(GM-CSF) and tumor necrosis factor α (TNFα) in enhancing the antibody-dependent cellular cytoxicity (ADCC) of the mAb 17-1A
and the mAb BR55-2 against the colorectal carcinoma cell line HT29. In experiments performed at an effector to target ratio
of 9:1, with peripheral blood mononuclear cells from five healthy volunteers as effector cells, we found that IFNα, IFNγ and
IL-2 significantly augmented the ADCC of both mAb at concentrations between 3 ng/ml and 30 ng/ml. The other three cytokines
were not effective. In further experiments we examined combinations of the three effective cytokines in different concentrations.
The combination of IFNα and IL-2 proved to be optimal in enhancing ADCC of both mAb. Thus, the examination of ADCC by flow
cytometry may reveal potentially useful combinations of cytokines and mAb for the treatment of colorectal carcinoma.
Received: 11 September 1997 / Accepted: 19 February 1998 相似文献
18.
Kiyoshi Asai Haruki Kato Shigeru Kimura Shigehiko Mukai Yutaka Kawahito Hajime Sano Motoharu Kondo Keiko Akaogi K. Hirose 《Cancer immunology, immunotherapy : CII》1996,42(5):275-279
We have elucidated the direct effects of PSK (a protein-bound polysaccharide) and OK-432 (a streptococcal preparation), both
immunomodulating drugs, on the gene expression for an inducible nitric oxide synthase and on the production of nitric oxide
(NO) in the RAW264.7 murine macrophage cell line. As determined by northern blot analysis, both immunomodulating drugs were
potent inducers of gene expression for inducible NO synthase when cells were costimulated with interferon-γ (IFNγ). Expression
of mRNA for the enzyme occurred in a dose-dependent manner after 3 h, when 10 – 50 μg/ml PSK or 0.001 – 1 KE/ml OK-432 was
used. Furthermore, NO was also produced in response to these drugs, as detected by the Griess reagent reaction. The enhancement
of NO synthesis was thought to be mediated, in part, through tumor necrosis factor α (TNFα) induction by these agents, since
a neutralizing antibody to TNFα significantly suppressed NO production in RAW264.7 cells stimulated with PSK or OK432 in combination
with IFNγ. We speculate that NO production may play a role in tumoricidal and microbicidal activities of PSK or OK-432 in
vivo.
Received: 9 August 1995 / Accepted: 1 April 1996 相似文献
19.
Ersvaer E Skavland J Ulvestad E Gjertsen BT Bruserud Ø 《Cancer immunology, immunotherapy : CII》2007,56(1):13-24
T cell targeting immunotherapy is now considered a possible strategy in acute myelogenous leukaemia (AML), and IFNγ release may then contribute to the antileukaemic effects. We investigated the effects of IFNγ on native human AML cells. Normal T cells could be activated to release IFNγ in the presence of AML cells. Furthermore, high levels of CD119 (IFNγ receptor α chain) expression were observed for all 39 patients examined. Receptor expression was decreased after exposure to exogenous IFNγ, and receptor ligation caused Stat1 phosphorylation but no phosphorylation of the alternative messengers Erk1/2. The effect of exogenous IFNγ on AML blast proliferation was dependent on the local cytokine network and IFNγ (1) inhibited proliferation in the presence of exogenous IL1β, GM-CSF, G-CSF and SCF; (2) had divergent effects in the presence of IL3 and Flt3 (65 patients examined); (3) inhibited proliferation in the presence of endothelial cells but had divergent effects in the presence of fibroblasts, osteoblasts and normal stromal cells (65 patients examined). IFNγ increased stress-induced (spontaneous) in vitro apoptosis as well as cytarabine-induced apoptosis only for a subset of patients. Furthermore, IFNγ decreased the release of proangiogenic CXCL8 and increased the release of antiangiogenic CXCL9–11. We conclude that IFNγ can be released in the presence of native human AML cells and affect AML cell proliferation, regulation of apoptosis and the balance between pro- and antiangiogenic chemokine release. 相似文献
20.
H. Yanagawa Takashi Haku Keiji Hiramatsu Hiroshi Nokihara Eiji Takeuchi Seiji Yano Masaki Hanibuchi Saburo Sone 《Cancer immunology, immunotherapy : CII》1997,45(2):93-99
The effect of intrapleural instillation of recombinant human interferon γ (IFNγ) at increasing doses of (1–12) × 106 U was examined in six patients with cytologically positive pleural effusion due to lung cancer. Intrapleural instillation
was repeated up to three times. Clinically, no reaccumulation of pleural effusion was observed in one patient and disappearance
of lung cancer cells from the pleural effusion was seen in two other patients. No severe side-effects were observed. Considerable
levels of IFNγ remained in the pleural effusion as well as in patients’ serum up to 7 days after instillation of 2 × 106 U and higher doses. The total cell number showed a transient decrease on day 1 of therapy. Levels of pro-inflammatory cytokines,
such as tumor necrosis factor α, interleukin(IL)-1β and IL-6, in the pleural effusion remained almost stable after IFNγ instillation.
On the other hand, intrapleural IL-1 receptor antagonist levels were remarkably elevated by the instillation of IFNγ. IL-2-
and IL-12-inducible killer activity of pleural mononuclear cells tended to increase slightly. Despite the inability of IFNγ
to control pleural effusion in this treatment schedule, IFNγ instilled by an intrapleural route had a potential local antitumor
activity. Moreover, since IFNγ persists in pleural effusions for a long time after a single instillation, such a therapy in
combination with other fibrogenic biological response modifiers can be promising.
Received: 28 February 1997 / Accepted: 23 July 1997 相似文献