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T Miseki,
H Kawakami,
M Natsuizaka,
S Darmanin,
H Y Cui,
J Chen,
Q Fu,
F Okada,
M Shindo,
F Higashino,
M Asaka,
J Hamuro, M Kobayashi
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ABSTRACT: We have recently reported that the intra-tumoral injection of adrenomedullin (AM) antagonist (AMA; AM (22-52)) peptides significantly reduced the in vivo growth of a pancreatic cancer cell line in severely combined immunodeficient (SCID) mice. In the present study, we examined the effects of intra-tumoral and intra-muscular transfers of naked DNA encoding AMA on the in vivo growth of cancer cell lines. We demonstrate that these treatments induce the regression of a pancreatic cancer cell line and a breast cancer cell line inoculated in SCID mice. Furthermore, CD31-positive cells disappear completely from tumor tissues, following treatment, indicating that neo-vascularization is entirely inhibited. These results suggest that the intra-tumoral or intra-muscular transfer of naked DNA encoding AMA might be a promising alternative modality for treating human cancers.
Cancer Gene Therapy 02/2007; 14(1):39-44. · 2.80 Impact Factor
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H Niizeki, M Kobayashi,
I Horiuchi,
N Akakura,
J Chen,
J Wang,
J-i Hamada,
P Seth,
H Katoh,
H Watanabe,
A Raz,
M Hosokawa
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ABSTRACT: The incidence of distant metastases is higher in the tumours with low oxygen pressure than in those with high oxygen pressure. It is well known that hypoxia induces the transcription of various genes involved in angiogenesis and anaerobic metabolism necessary for the growth of tumour cells in vivo, suggesting that hypoxia may also induce the transcription of metastasis-associated genes. We sought to identify the metastasis-associated genes differentially expressed in tumour cells under hypoxic conditions with the use of a DNA microarray system. We found that hypoxia enhanced the expression of autocrine motility factor mRNA in various cancer cells and also enhanced the random motility of pancreatic cancer cells. Autocrine motility factor inhibitors abrogated the increase of motility under hypoxic conditions. In order to explore the roles of hypoxia-inducible factor-1alpha, we established hypoxia-inducible factor-1alpha-transfectants and dominant negative hypoxia-inducible factor-1alpha-transfectants. Transfection with hypoxia-inducible factor-1alpha and dominant-negative hypoxia-inducible factor-1alpha enhanced and suppressed the expression of autocrine motility factor/phosphohexase isomerase/neuroleukin mRNA and the random motility, respectively. These results suggest that hypoxia may promote the metastatic potential of cancer cells through the enhanced autocrine motility factor/phosphohexase isomerase/neuroleukin mRNA expression and that the disruption of the hypoxia-inducible factor-1 pathway may be an effective treatment for metastasis.
British Journal of Cancer 07/2002; 86(12):1914-9. · 5.04 Impact Factor
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ABSTRACT: Hypovasculature is an outstanding characteristic of pancreatic cancers in imaging diagnosis, suggesting that blood supply is poor in pancreatic cancer tissues. Despite poor blood supply, pancreatic cancer cells survive and proliferate in severe hypoxia and nutrient deprivation. To demonstrate how pancreatic cancer cells adapt themselves to hypoxia and nutrient deprivation, we investigated the expression of hypoxia-inducible factor 1alpha (HIF-1alpha) protein and HIF-1-inducible genes in human pancreatic cancer cell lines in comparison with other cancer cell lines. We found that HIF-1alpha protein was constitutively expressed in 15 of 20 pancreatic cancer cell lines (75%) but in none of other cancer cell lines tested in this study. The cells with constitutive expression of HIF-1alpha were more resistant to apoptosis induced by hypoxia and glucose deprivation than those without constitutive expression of HIF-1alpha. Transfection with HIF-1alpha transformed the latter cells resistant to apoptosis and increased in vivo tumorigenicity. Furthermore, anaerobic metabolism-associated genes, Glut1 and aldolase A, were more highly expressed in the cells with constitutive expression of HIF-1alpha than in the cells without it. These results suggest that constitutive expression of HIF-1alpha contributes to the survival and proliferation of pancreatic cancer cells in hypoxia and glucose deprivation through the activation of anaerobic metabolism.
Cancer Research 10/2001; 61(17):6548-54. · 7.86 Impact Factor
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Transplantation Proceedings 12/2000; 32(7):2452-3. · 1.00 Impact Factor
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Transplantation Proceedings 12/2000; 32(7):2448-9. · 1.00 Impact Factor
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ABSTRACT: We investigated the expression of natural killer cell receptors (NKRs) for HLA-C on peripheral blood mononuclear cells (PBMCs) in 23 allogeneic bone marrow transplantation (allo-BMT) patients to analyse the role of NKRs in alloresponse concerning graft-versus-host disease (GVHD). CD158a expression was low and there was little change in the expression after allo-BMT. Also, there was no difference in the proportion of CD158a+/CD3- after allo-BMT. In contrast, the proportion of CD158b+/CD3- cells, mainly NK cells, increased in the early stage (< 2 months) after allo-BMT and then gradually decreased (3.3 +/- 2.6% before BMT vs. 15.4 +/- 8. 6% in the early stage after BMT, 8.5 +/- 4.9% during the period 3-6 months after BMT and 7.0 +/- 3.0% > 6 months after BMT; P < 0.05). However, CD158b expression on CD3+ T cells increased 3 months after allo-BMT (1.1 +/- 1.1% before BMT vs. 5.1 +/- 7.7% during the period 3-6 months after BMT and 3.0 +/- 2.4% > 6 months after BMT, P < 0. 05). The highest percentages of CD158 expression in patients without chronic GVHD (cGVHD) and those with cGVHD were compared. The percentage of CD158b+/CD3+ cells and also that of CD158b+/CD8+ cells were significantly increased in patients with cGVHD compared with those in patients without cGVHD (2.6 +/- 2.0% vs. 8.0 +/- 11.2% and 2.3 +/- 1.5% vs. 8.3 +/- 11.7% respectively; P < 0.05). The exact clinical relevance of these CD158b-expressing cells is not clear. However, there is an interesting possibility that CD158b-expressing cells play some role in the regulation of GVHD after allo-BMT.
British Journal of Haematology 03/2000; 108(4):778-83. · 4.94 Impact Factor
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ABSTRACT: Metastasis frequently occurs during and/or after chemotherapy resulting in failure. This suggests that inadequate chemotherapy promotes the emergence of more malignant tumor cells with metastatic potential. However, it is not determined how chemotherapy could promote the metastatic progression of tumor cells. In this study, we isolated highly metastatic clones from the tumors treated with ADR using an in vivo experimental model, in which non-metastatic tumor cells were inoculated s.c. in mice, treated with or without Adriamycin and then culture lines were re-established from the tumors. Then we isolated cDNAs for activated leukocyte cell adhesion molecule (ALCAM), osteopontin, and annexin II as candidates for metastasis-promoting genes with the use of a PCR-based subtraction method. Further we examined the metastatic potential of transfectants over-expressing ALCAM, osteopontin, or annexin II and combinations of them. Metastasis to the lung was observed in the mice where transfectants over-expressing ALCAM plus annexin II had been inoculated via tail vein. These results suggest that the over-expression of ALCAM and annexin II play a role in the metastatic progression after chemotherapy with ADR.
Clinical and Experimental Metastasis 02/2000; 18(1):45-50. · 3.52 Impact Factor
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K Imai, M Kobayashi,
J Wang,
N Shinobu,
H Yoshida,
J Hamada,
M Shindo,
F Higashino,
J Tanaka,
M Asaka,
M Hosokawa
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ABSTRACT: To elucidate the mechanisms by which haemopoietic progenitor cells lodge in the bone marrow, we examined the secretion of chemoattractants for haemopoietic progenitor cells by bone marrow and lung endothelial cells. The bone marrow endothelial cells, but not lung endothelial cells, secreted chemoattractants for the haemopoietic progenitor cell line, FDCP-2, and normal haemopoietic progenitor cells. Checkerboard analysis demonstrated that the conditioned medium of the bone marrow endothelial cells had chemotactic activity and random motility-stimulating activity. The bone marrow endothelial cells expressed stromal-cell-derived factor-1 (SDF-1) mRNA and produced SDF-1 protein, whereas the lung endothelial cells did not. Adhesion of FDCP-2 cells to the bone marrow endothelial cells was partially inhibited by anti-SDF-1 antibody. These findings suggest that the chemoattractants for haemopoietic progenitor cells including SDF-1 and random motility-stimulating factor(s) selectively secreted by the bone marrow endothelial cells may contribute to the homing of haemopoietic progenitor cells to bone marrow.
British Journal of Haematology 10/1999; 106(4):905-11. · 4.94 Impact Factor
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ABSTRACT: We have shown that metastasis is suppressed by low-dose total-body irradiation (TBI) in tumor-bearing rats. We have evaluated the immunological effects of low-dose TBI. Total-body irradiation with 0.2 Gy was given 14 days after the implantation of 5 x 10(5) allogenic hepatoma cells (KDH-8) which produce transforming growth factor beta (TGF-beta). On day 21, the splenocytes and tumor-tissue infiltrating lymphocytes were analyzed by FACScan and RT-PCR for the mRNA of the genes that encode tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), TGF-beta, interleukin (IL)-4, IL-10 and IL-6. The same procedure was conducted with untreated rats and with rats that underwent local irradiation with 0.2 Gy. The low-dose TBI significantly decreased the incidence of lung and lymph node metastasis (P < 0.01), whereas the same dose of local irradiation had no effect on the incidence of metastasis. The proportion of CD8+ cells in splenocytes increased in the low-dose TBI group (P < 0.01) compared to the locally irradiated and the untreated groups. The tumor-tissue infiltrating lymphocytes were also significantly increased after low-dose TBI (P < 0.01). The FACScan analysis revealed that 72% of the tumor-tissue infiltrating lymphocytes were CD8+. In both spleen and tumor tissue after low-dose TBI, mRNA expression of the genes that encode IFN-gamma and TNF-alpha increased, while that of the Tgfb gene decreased. There was no expression of the mRNAs of the Il4, Il6 and Il10 genes. CD8+ cells and the cytokine network may play an important role in the antitumor effect of low-dose TBI.
Radiation Research 06/1999; 151(6):717-24. · 2.68 Impact Factor
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H Habelhah,
F Okada, M Kobayashi,
K Nakai,
S Choi,
J Hamada,
T Moriuchi,
M Kaya,
K Yoshida,
K Fujinaga,
M Hosokawa
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ABSTRACT: In this study, we investigated the role of E1AF, a member of ets family transcription factor, in the acquisition of metastatic capacity by non-metastatic mouse fibrosarcoma cell clone, QR-32. The QR-32 cell clone grows progressively after co-implantation with gelatin sponge in syngeneic C57BL/6 mice. The cell lines (QRsP) established from arising tumors after the co-implantation exhibited enhanced tumorigenicity and pulmonary metastasis in vivo as compared with parent QR-32 cells. The enhanced pulmonary metastasis of QRsP cells was correlated well with augmented production of matrix metalloproteinase-2 (MMP-2) and increased expression of membrane-type 1-MMP (MT1-MMP). The QRsP cells also acquired higher chemokinetic activities to fibronectin and higher invasive activities through a reconstituted basement membrane. Furthermore we observed the elevated mRNA expression of E1AF in QRsP cells compared to parent QR-32 cells. Therefore, we transfected QR-32 cells with E1AF cDNA. Overexpression of E1AF in the QR-32 cells resulted in the induction of MT1-MMP expression and converting an exogenously added precursor MMP-2 into active form. E1AF transfectants exhibited more motile and invasive activities, and moderately increased pulmonary metastatic activities than parental QR-32 cells in vivo, although their metastatic activities were lower than those of QRsP cells. These findings suggest that the increased expression of E1AF in fibrosarcoma contributes to invasive phenotypes including MT1-MMP expression and enhanced cell migration, but not sufficient for exhibiting highly metastatic activity in vivo.
Oncogene 04/1999; 18(9):1771-6. · 6.37 Impact Factor
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ABSTRACT: To elucidate the roles of chemotherapeutic agents in tumor progression, we examined whether cis-diamminedichloroplatinum (II) (cisplatin) and UFT would promote malignant progression of a weakly tumorigenic and poorly metastatic fibrosarcoma cell line OR-32SK in vivo. C57BL/6 mice, transplanted with QR32SK, were treated with either cisplatin or UFT alone and in combination. After treatment with or without cisplatin and/or UFT, we established in vitro culture cell lines from the tumors arising in the mice on day 21 and then i.v. injected the established cell lines into syngeneic mice. As a result, the cell lines established from cisplatin-treated mice and UFT-treated mice had significantly higher metastatic capacity in lung compared to the ones from control untreated mice (64 and 65%, respectively, versus 26.7%). The cell lines established from the mice with the combination therapy showed lower lung metastasis (11%) than the ones from control untreated mice. Furthermore, we found the incidences of these experimental metastases were closely related with in vitro chemotactic activities and the production of MMP-9 of the cultured cell lines. These results indicate that cisplatin and UFT as a single agent promote the chemotactic activities and the production of MMP-9 in non-metastatic fibrosarcoma cells, resulting in the conversion to highly metastatic ones, and that cisplatin and UFT in combination failed to promote the chemotactic activities and the conversion. These results suggest that the combination therapy with cisplatin and UFT is useful in preventing the emergence of more malignant tumor cells after chemotherapy.
Anti-Cancer Drugs 03/1999; 10(2):235-43. · 2.41 Impact Factor
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K Imai, M Kobayashi,
J Wang,
Y Ohiro,
J Hamada,
Y Cho,
M Imamura,
M Musashi,
T Kondo,
M Hosokawa,
M Asaka
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ABSTRACT: To elucidate the mechanisms by which hematopoietic progenitor cells transmigrate via the bone marrow (BM) endothelial cells, we first established endothelial cell lines from BM and lung, and BM fibroblast cell lines; then we established an in vitro model of transendothelial migration of hematopoietic progenitor cells in the presence of chemoattractants secreted by BM fibroblast cells. The BM endothelial cells expressed vascular cell adhesion molecule-1 (VCAM-1), but the lung endothelial cells did not. The BM fibroblast cells secreted chemoattractants including stroma cell-derived factor (SDF)-1, which could attract hematopoietic progenitor cells to BM and activate the adhesion molecules expressed on hematopoietic progenitor cells after rolling along the endothelial cells. Anti-SDF-1 antibody inhibited the transendothelial migration of a hematopoietic progenitor cell line, FDCP-2. FDCP-2 that expressed very late activation antigen-4 (VLA-4) and normal progenitor cells transmigrated through BM endothelial cells but not lung endothelial cells, even if in the presence of chemoattractants produced by BM fibroblasts. Both anti-VLA-4 and anti-VCAM-1 antibodies inhibited the transendothelial migration of FDCP-2 cells and normal hematopoietic progenitor cells. These findings suggest that the transendothelial migration of hematopoietic progenitor cells is characteristic of BM endothelial cells, and that VLA-4/VCAM-1 and SDF-1 play important roles in the transendothelial migration and, consequently, homing of hematopoietic progenitor cells to BM.
Blood 02/1999; 93(1):149-56. · 9.90 Impact Factor
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ABSTRACT: 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 alpha (TNFalpha) and interleukin-1alpha (IL-1alpha) were considerably expressed in both PSK-treated and phosphate-buffered-saline-treated tumors, and that the mRNA expression and protein level of interferon gamma (IFNgamma) increased in the tumor tissues treated with PSK. In vitro treatment of QR-32 cells with IFNgamma did not significantly increase the production of Mn-SOD; however, the combination of IFNgamma with TNFalpha 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 beta (TGFbeta) in the tumor tissues treated with PSK, and that in vitro treatment of QR-32 cells with TGFbeta 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-beta and increasing IFN-gamma.
Cancer Immunology and Immunotherapy 09/1998; 46(6):338-44. · 3.70 Impact Factor
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ABSTRACT: A cytotoxic T-cell line, CTLL-2 cells, showed spreading after adhering to extracellular matrix proteins such as fibronectin (FN), laminin (LN) and hyarulonic acid (HA). The adhesion of CTLL-2 cells to LN was mediated by very late activation antigen-6 (VLA-6). Expression of interferon-gamma (IFN-gamma) mRNA was enhanced in CTLL-2 cells, also when they adhered to extracellular matrix proteins; and the enhanced IFN-gamma mRNA expression by adhering to LN was blocked by anti-alpha 6 antibody. Calphostin C, a protein kinase C (PKC) inhibitor, markedly inhibited the enhancement of IFN-gamma mRNA expression in a dose-dependent manner, which suggested that PKC acted as a second messenger in the IFN-gamma mRNA expression mediated by the interaction of VLA-6 with LN in CTLL-2 cells. Furthermore, confocal laser-microscopic analysis and Western blot analysis revealed that PKC-alpha was activated after CTLL-2 cells adhered to LN. PKC activity translocated from the cytosol fraction to the particulate fraction, after CTLL-2 cells adhered to LN. Altogether, we suggest that PKC plays an important role in the signal transduction for IFN-gamma mRNA expression after cytotoxic T cells adhere to LN.
Immunology 05/1998; 93(4):455-61. · 3.32 Impact Factor
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ABSTRACT: Synergistic effects of active hexose correlated compound (AHCC) extracted from mushroom on the treatment with UFT against mammary adenocarcinoma, SST-2 cells, in congenitally T cell-depressed spontaneously hypertensive rats (SHR) were observed. AHCC plus UFT had slight but significant effects on the growth of primary tumors. Pulmonary metastases were not inhibited by the treatment with AHCC plus UFT, whereas metastases to axillary lymph nodes (LN) were obviously inhibited. Combination of AHCC plus UFT showed similar synergistic anti-metastatic effects in SHR rats with accelerated pulmonary metastases following the surgical removal of the primary tumors. In vitro studies demonstrated that AHCC plus UFT enhanced the NK cell activity in tumor-bearing rats, whereas UFT alone depressed the NK cell activity. AHCC plus UFT also enhanced the NO production and cytotoxicity of peritoneal macrophages. In addition, AHCC restored the suppressed mRNA expression of interleukin-1alpha and tumor necrosis factor-alpha induced by the chemotherapy. Taken together, the combination of AHCC plus UFT brought about good therapeutic effects not only on primary tumor growth but also on reducing metastasis and these effects were mediated by host immunity which was restored or activated by AHCC. AHCC may be a good candidate for a biological response modifier.
Anti-Cancer Drugs 05/1998; 9(4):343-50. · 2.41 Impact Factor
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ABSTRACT: We investigated the therapeutic effects of ONO-4007, a novel synthetic lipid A derivative with low toxic activities, on transplanted hepatocellular carcinoma KDH-8 in WKAH rats. ONO-4007 brought about complete cures in about 60% of rats bearing tumor necrosis factor (TNF)-alpha-sensitive KDH-8 cells, whereas no complete cure was observed in rats bearing cKDH-8/11 which is identical to KDH-8 but a TNF-alpha-resistant cell line, KMT-17 and KEG-1. Then we examined the influence of rabbit anti-TNF-alpha antibody on the therapeutic effects of ONO-4007 against the TNF-alpha-sensitive KDH-8. The concomitant administration of the rabbit anti-TNF-alpha antibody completely abrogated the therapeutic effects of ONO-4007. On the other hand, rechallenged tumor cells of both KDH-8 and cKDH-8/11 were completely rejected in the rats cured of KDH-8 tumor, although no rejection of KEG-1 was observed. Moreover, Winn assay, i.e. the tumor cell neutralizing assay, indicated that CD4+ T cells were involved in the antigen-specific transplantation resistance. These findings suggest that antigen-specific T cell responses are involved in the complete cure of tumors after the treatment with ONO-4007, although its therapeutic effect is initiated by TNF-alpha.
Anti-Cancer Drugs 04/1998; 9(3):273-82. · 2.41 Impact Factor
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ABSTRACT: We examined the effects of epidermal growth factor (EGF) on tumor progression of a weakly malignant rat mammary carcinoma cell line, ER-1. In vitro treatment with EGF enhanced tumorigenicity, metastatic capacity and in vitro invasive capacity of ER-1 cells. The increased malignancy of ER-1 cells was reversible, when the cells were pretreated with EGF for 24 h, whereas it was irreversible when pretreated with EGF for 1 month. EGF treatment elevated the intracellular peroxide level in ER-1 cells. When ER-1 cells were treated with EGF in the presence of N-acetylcysteine, a chemical antioxidant, the reversible or irreversible EGF-induced progression was inhibited. These results suggest that the reversible or irreversible tumor progression in ER-1 cells occur in accordance with the duration of exposure to EGF, and that reactive oxygen species may be involved in the progression.
International Journal of Oncology 02/1998; 12(1):197-202. · 2.40 Impact Factor
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ABSTRACT: To explore the mechanisms of immuno-modulatory activities of bleomycin, we investigated interferon gamma (IFN gamma) mRNA expression, tumor necrosis factor alpha (TNF alpha) 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 beta (TGF beta), and these processes in KDH-8 tumor-bearing rats treated with bleomycin. We found that IFN gamma mRNA expression, TNF alpha 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, IFN gamma mRNA expression and TNF alpha production in the KDH-8-bearing rats. In vitro experiments showed that KDH-8-derived TGF beta decreased the IFN gamma mRNA expression and TNF alpha 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 TGF beta.
Cancer Immunology and Immunotherapy 11/1997; 45(2):71-6. · 3.70 Impact Factor
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ABSTRACT: ONO-4007 is a new synthetic lipid A derivative with low endotoxic activities. ONO-4007 was effective against KDH-8, a tumor necrosis factor (TNF)-sensitive rat hepatoma cell line, but neither effective against KMT-17, a TNF-resistant rat fibrosarcoma cell line, nor SST-2, a TNF-resistant rat mammary adenocarcinoma cell line. We have established two sublines from KDH-8 to further examine the therapeutic mechanisms of ONO-4007 in vivo: TNF-sensitive KDH-8/YK and TNF-resistant cKDH-8/11. The two sublines equally proliferated in vitro. Multiple systemic i.v. administration of ONO-4007 was performed on days 7, 14 and 21 after tumor implantation. Although treatment with ONO-4007 had no effect on the growth of cKDH-8/11 in WKAH rats in vivo, 60% of KDH-8/YK-bearing rats treated with ONO-4007 survived. The administration of ONO-4007 brought about significant therapeutic effects on KDH-8/YK-bearing rats but not on cKDH-8/11-bearing rats. These results suggest that ONO-4007 is therapeutically useful for the treatment of TNF-alpha-sensitive tumors.
Anti-Cancer Drugs 11/1997; 8(9):898-901. · 2.41 Impact Factor
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ABSTRACT: ONO-4007 is a new synthetic lipid A analog with low endotoxic activities. We previously found that ONO-4007 induced the production of tumor necrosis factor (TNF)-alpha in rat hepatoma KDH-8 tumor tissues and brought about the regression of transplanted KDH-8 cells. By contrast, ONO-4007 did not induce TNF-alpha production in spleens and sera 90 min after treatment. In the present study we attempted to elucidate how ONO-4007 induces TNF-alpha production in tumor tissues locally. We found that extracellular matrix including gelatin, fibronectin and Matrigel did not induce TNF-alpha production in splenocytes treated with ONO-4007 in vitro. However, splenocytes co-cultured with cKDH-8/11 tumor cells in the presence of ONO-4007 produced more TNF-alpha than splenocytes cultured by themselves in the presence of ONO-4007. The stimulation of cKDH-8/11 cells in the presence of ONO-4007 for splenocytes to produce TNF-alpha depended on the type of contact between the cells. The cKDH-8/11 cells fixed in formalin were not able to induce TNF-alpha production of splenocytes even in the presence of ONO-4007. However, syngeneic fibrosarcoma cell line KMT-17/A3, allogeneic hepatocellular carcinoma cell line LDH and rat lung endotherial cell line RLE induced TNF-alpha production in splenocytes, but their stimulation was weaker than that of cKDH-8/11. The soluble form of the cKDH-8/11 cell membrane did not stimulate splenocytes to produce TNF-alpha in the presence of ONO-4007. cKDH-8/11 cells did not stimulate the splenocytes devoid of macrophages to produce TNF-alpha in the presence of ONO-4007.
Anti-Cancer Drugs 11/1997; 8(9):886-93. · 2.41 Impact Factor
