Biomedical subjects

Junichiro Mizuguchi

Publications and source records attributed to Junichiro Mizuguchi.

At least 37 records · Page 2Linked to original sources

PubMed2004

Synergistic antitumor effect by coexpression of chemokine CCL21/SLC and costimulatory molecule LIGHT.

To establish a more efficient treatment for immunotherapy against solid tumors, we have evaluated the antitumor effect by coexpression of a chemokine CCL21/secondary lymphoid tissue chemokine and a costimulatory molecule LIGHT in colon carcinoma C26. C26 cells expressing either CCL21 or LIGHT exhibited a significantly reduced tumor growth in vivo, and mice inoculated with these cells showed a prolonged survival, but eventually all these mice died. In contrast, C26 cells expressing both CCL21 and LIGHT exhibited a minimal tumor growth in vivo, and all these mice survived healthily with a tumor remission and consequently acquired a strong protective immunity. A markedly increased infiltration of mature dendritic cells (DCs), and CD8(+) T cells was observed in the tumor mass, and their spleen cells showed a greatly enhanced cytotoxic T lymphocyte (CTL) activity against C26 tumor and interferon (IFN)-gamma production. Neutralization of IFN-gamma or depletion of CD8(+) or CD4(+) T cells significantly reduced the antitumor activity. These results suggest that the combined treatment with CCL21 and LIGHT is able to induce a synergistic antitumor effect to eradicate tumor completely by greatly enhancing tumor-infiltration of lymphocytes including mature DCs and CD8(+) T cells, resulting in markedly augmented CTL activity and IFN-gamma production.

Animals↗

PubMed2003

CD27 synergizes with CD40 to induce IgM, IgG, and IgA antibody responses of peripheral blood B cells in the presence of IL-2 and IL-10.

CD40, a member of the tumor necrosis factor receptor (TNFR) family, promotes IgM, IgG, and IgA antibody (Ab) synthesis in combination with a variety of cytokines. Another TNFR family member, CD27, causes B cells to differentiate into antibody-forming cells, with marginal effects on proliferation. In the present study, we examined whether anti-CD27 monoclonal antibody (mAb) modulates the antibody production induced by anti-CD40 mAb immobilized on L cells expressing FcgammaRII (CDw32) in the presence of IL-2 and/or IL-10. The anti-CD40 mAb substantially enhanced IgM, IgG, and IgA production in combination with IL-2 and IL-10, whereas anti-CD27 mAb augmented it only marginally, as assessed by enzyme-linked immunosorbent assay. The addition of anti-CD27 mAb enhanced the anti-CD40-mediated IgM, IgG, and IgA antibody production only when both IL-2 and IL-10 were present in the culture. The CD27-positive B cell compartment generated synergistic antibody responses in response to four different stimulants, anti-CD27/anti-CD40 mAb and cytokines IL-2/IL-10, whereas the CD27-negative B cell compartment failed to do so. Kinetic analysis showed that anti-CD40 might function in the early phase of B cell activation, while anti-CD27 mAb functioned in the late stage. The addition of CD27(-) to CD27(+) B cells in various ratios did not have any effect on the antibody production, suggesting that CD27(+) to CD27(-) B cell interaction does not occur in this system. Our findings suggest that a member of the TNFR family, CD27, cooperates with CD40 to induce efficient antibody production in combination with cytokines IL-2 and IL-10.

Antibodies↗

PubMed2003

Positive modulation of IL-12 signaling by sphingosine kinase 2 associating with the IL-12 receptor beta 1 cytoplasmic region.

IL-12 is a key immunoregulatory cytokine that promotes Th1 differentiation and cell-mediated immune responses. IL-12 stimulation results in the activation of Janus kinase 2 and tyrosine kinase 2 and, subsequently, STAT4 and STAT3. In addition, mitogen-activated protein kinase kinase 6/p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt pathways have been recently demonstrated to be activated by IL-12 and play an important role in IL-12 signaling. To further elucidate the molecular mechanism underlying IL-12 signaling, we have performed a yeast two-hybrid screening and identified mouse sphingosine kinase 2 (SPHK2) as a molecule associating with the mouse IL-12Rbeta1 cytoplasmic region. Analyses of various mutants of each molecule revealed that the region including the proline-rich domain in SPHK2 is probably responsible for the binding to IL-12Rbeta1, while the regions including the carboxyl terminus and Box II in the IL-12Rbeta1 cytoplasmic region appear to be involved in the binding to SPHK2. Transient expression of wild-type SPHK2 in T cell hybridoma augmented IL-12-induced STAT4-mediated transcriptional activation. Ectopic expression of dominant-negative SPHK2 in Th1 cell clone significantly reduced IL-12-induced IFN-gamma production, while that of wild-type SPHK2 enhanced it. In contrast, the expression minimally affected IL-12-induced proliferation. A similar decrease in IL-12-induced IFN-gamma production was observed when dominant-negative SPHK2 was expressed in activated primary T cells using a retroviral expression system. These results suggest that SPHK2 associates with the IL-12Rbeta1 cytoplasmic region and probably plays a role in modulating IL-12 signaling.

Amino Acid Sequence↗

PubMed2003

Calpain-induced Bax-cleavage product is a more potent inducer of apoptotic cell death than wild-type Bax.

Wild type (wt) p21 Bax was cleaved to generate p18 Bax during apoptotic processes by calpain, which was suggested to recognize a certain motif around amino acids 30-33 Phe-Ile-Gln-Asp (FIQD). In the present study, analysis of protein sequencing revealed that the cleavage site was between Gln28 and Gly29. The fragment lacking the NH(2)-terminal amino acids 1-28 (tBax(29)) was more apoptotic than wt Bax. The tBax(29)-induced apoptotic cell death was substantially resistant to Bcl-x(L)-mediated rescue, compared with wt Bax, in spite of the complex formation between these two molecules. Together, the tBax(29) would be valuable for the treatment of tumors with high levels of Bcl-x(L) as well as the understanding of Bax-mediated apoptotic processes.

Adenocarcinoma↗

PubMed2003

Modulation of mThy28 nuclear protein expression during thymocyte development.

We have recently shown that down-regulation of mouse Thy28 (mThy28) protein expression appears to be accompanied by apoptotic processes. Thymocytes from mice contain moderate amounts of mThy28 protein and undergo proliferation, differentiation, or apoptosis during murine thymic maturation. As a first step to examine the potential role of the mThy28 protein in the thymocyte development, such as positive-negative selection, the expression of mThy28 protein in the thymocyte subsets was examined. Thymocytes are separated into four subpopulations by the expression levels of CD4 and CD8: CD4-CD8- (DN), CD4+CD8+ (DP), and CD4+CD8- or CD4-CD8+ (SP). Flow cytometry analysis using three-color staining demonstrated that the mThy28 expression in immature DP cells is lower than that in DN and SP cells. The down-regulation of the mThy28 expression in the DP stage was also detected by Western blotting and reverse transcription-polymerase chain reaction (RT-PCR). The immunostaining method also showed that mThy28 protein was expressed in the medulla containing mature thymocytes, but not the cortex having immature thymocytes. The mThy28 protein in the thymocytes was mainly localized in the nucleus, as recently demonstrated in lymphoma cells, indicating that the mThy28 protein resides in the nucleus, irrespective of the cyclic or resting stage of the cell cycle. Together, the observation that mThy28 expression is down-modulated during the DP stage suggests that mThy28 protein might play some role in the positive-negative selection step in thymic maturation.

Animals↗

PubMed2003

Chemotherapeutic agents sensitize sarcoma cell lines to tumor necrosis factor-related apoptosis-inducing ligand-induced caspase-8 activation, apoptosis and loss of mitochondrial membrane potential.

Chemotherapeutic agents have been used for the treatment of patients with osteosarcoma (OS). However, inherent or acquired resistance to these agents is a serious problem in the management of OS patients. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered to induce apoptosis in a variety of cancer cells but not normal cells. In the present study, we examined whether chemotherapeutic agents enhance TRAIL-induced apoptosis in the sarcoma cell lines MG-63 and SaOS-2. Pretreatment with sub-toxic or slightly toxic concentrations of chemotherapeutic agents (cis-diammine dichloroplatinum, CDDP and doxorubicin, DXR) sensitized both cell lines to TRAIL-induced apoptosis, as assessed by the propidium iodide or Annexin V-Cy5 staining method. These cell lines expressed death receptors TRAIL-receptor 1 (TRAIL-R1) and TRAIL-R2, which were unaltered by treatment with CDDP, as assessed by flow cytometry. The decoy receptors TRAIL-R3 and -R4 were barely detected in both cell lines. CDDP down-regulated c-FLIP, tending to lower the activation threshold required for TRAIL-induced caspase-8 activation. The CDDP-pretreated cells indeed demonstrated more increased TRAIL-mediated caspase-8 activation, loss of mitochondrial membrane potential (DeltaPsi(m)), and apoptosis than untreated cells. Consequently, the activated caspase-8 might lead to either activation of effector caspases such as caspase-3 or loss in DeltaPsi(m). Both the increased caspase activation and mitochondrial dysfunction induced by combination of CDDP and TRAIL would contribute to enhanced apoptotic cell death. The results of the present study would be valuable for the design of novel treatment modalities for patients with OS.

Antineoplastic Agents↗

PubMed2003

Turnover of acinar and islet cells in the pancreas of monosodium glutamate-treated obese mice.

OBJECTIVE: Subcutaneous administrations of monosodium glutamate (MSG) to neonatal animals result in obesity and induce the toxicity on the central nervous system, and furthermore, have an effect on entero-pancreatic hormone. The effect of MSG on the cell turnover of organs, especially the pancreas, has received little attention until now. This study was designed to examine the effect of MSG on pancreatic cell turnover by immunohistochemistry and [(3)H]thymidine autoradiography. RESEARCH METHODS AND PROCEDURES: Male JcI-ICR strain mice were SC injected with MSG (2 mg/g body weight daily) for 5 days after birth, received 112 repeated injections of [(3)H]thymidine at 6-hour intervals for 28 days after birth, and then were killed immediately thereafter, or 30, 60, or 120 days after the last injection. Autoradiography was performed on sections immunostained for glucagon, insulin, and somatostatin. RESULTS: After continuous labeling, most pancreatic cells were labeled, and thereafter, labeling of cells decreased in control and MSG-treated mice. The mean grain counts of acinar cells in MSG-treated mice decreased more slowly than those in control mice. On the other hand, those of islet cells, including glucagon, insulin, and somatostatin cells, decreased more rapidly in MSG-treated mice than those in control mice. DISCUSSION: Cell turnover of acinar cells was decelerated and that of islet cells including glucagon, insulin, and somatostatin cells was accelerated in MSG-treated mice pancreas. MSG-induced hypothalamic lesions exert the contrary influences on the cell turnover of acinar and islet cells.

Animals↗

PubMed2003

Induction of apoptosis and/or necrosis following exposure to antitumour agents in a melanoma cell line, probably through modulation of Bcl-2 family proteins.

Malignant melanoma cells have been reported to be highly resistant to chemotherapeutic agents. To gain insight into the molecular mechanisms underlying chemotherapeutic drug resistance, we examined the role of the Bcl-2 family members Bcl-2 and Bax in cell death in the melanoma cell line G361 following stimulation with cisplatin (CDDP) or dacarbazine (DTIC). Trypan blue dye exclusion showed that both CDDP and DTIC induced death of G361 cells. Apoptotic and necrotic cell death could be distinguished by flow cytometry using combined staining with annexin V and 7-amino-actinomycin D (7-AAD). CDDP-induced cell death at a low concentration (0.6 micro g/ml) was mainly due to apoptosis (annexin V+/7-AAD-), while a mixture of apoptosis and secondary necrosis (annexin V+/7-AAD+) was found at a high concentration (6 micro g/ml). DTIC at the concentrations used induced only apoptosis. CDDP-induced apoptosis and secondary necrosis were accompanied by activation of caspase-3 and modulation of Bcl-2 family members Bcl-2 and Bax. On Western blotting Bax was seen to be upregulated with concomitant downregulation of Bcl-2. Flow cytometry, which enables measurement of protein at the single-cell level, revealed that Bcl-2+/Bax- cells were decreased, with a slight concomitant rise in Bcl-2-/Bax+ cells on stimulation with CDDP. These findings suggest that the chemotherapeutic agents CDDP and DTIC induce apoptosis and/or secondary necrosis depending on dose, probably involving the modulation of Bcl-2 family proteins.

Annexin A5↗

PubMed2003

Efficient gene transfer to hepatoblastoma cells through asialoglycoprotein receptor and expression under the control of the cyclin A promoter.

Specific gene delivery into hepatoma cells by liposomes and specific gene expression under the control of the cyclin A promoter were examined in HepG2 cells, a hepatoblastoma cell line that overexpresses cyclin A. A plasmid carrying the luciferase gene under the cyclin A promoter sequence was condensed with poly-L-lysine and encapsulated into anionic asialofetuin-labeled liposomes (AF-liposomes), which were preferentially taken up by hepatocytes through the action of the asialoglycoprotein receptor (AgpR). AF-liposomes delivered plasmids to the hepatoma cells by receptor-mediated endocytosis through the AgpR, and transgene expression could be achieved under the control of the cyclin A promoter. Furthermore, a fusogenic lipid, DOPE, as a liposomal component was required for the enhancement of transfection efficiency of AF-liposomes.

Antimalarials↗

PubMed2003

Enhanced expression of the apoptosis inducing ligand TRAIL in mononuclear cells after myocardial infarction.

Tumor necrosis factor (TNF) family proteins including TNF-alpha and Fas (CD95)-ligand have been implicated in the development of acute myocardial infarction (AMI). We studied whether AMI patients displayed up-regulation of another TNF family member, TNF-related-apoptosis-inducing ligand (TRAIL), on peripheral blood mononuclear cells (PBMCs). We compared expression of TRAIL on PBMCs from 26 patients in the acute phase of AMI with that on PBMCs from 16 healthy control subjects using flow cytometry and RT-PCR. In addition, expression of TRAIL protein on PBMCs from patients in the acute phase of AMI was also compared with that from the same patients 7 days later. Furthermore, we compared the expression of TRAIL protein on CD4+, CD8+, CD14+, and CD19+ cells from patients in the acute phase of AMI with that from control subjects using flow cytometry. Finally, expression of the TRAIL receptors (TRAILR)-1 and TRAILR-2 in human cardiomyocytes was examined immunohistochemically. Expression of TRAIL protein was significantly higher in the acute phase of AMI than in control subjects. Expression of TRAIL protein was significantly higher in the acute phase of AMI than 7 days later. TRAIL mRNA expression in the acute phase of AMI was higher than in control subjects. Expression of TRAIL protein on CD4+ and CD14+ cells from AMI patients was significantly higher than that from control subjects. Expression of TRAILR-1 and TRAILR-2 in human cardiomyocytes was confirmed immunohistochemically. TRAIL on infiltrating CD4 and CD146 cells may be involved in the induction of cardiomyocyte apoptosis after AMI.

Apoptosis↗

PubMed2002

Molecular cloning and characterization of the mouse thymocyte protein gene.

Chicken thymocyte protein (cThy28) has recently been identified and implicated to be involved in apoptosis of avian lymphocytes, while its functional role remains undefined. To elucidate the role of Thy28, we have molecularly cloned the mouse Thy28 (mThy28) cDNA and clarified its genomic organization in the present study. The mThy28 cDNA encodes a 226 amino acid protein, whose sequence is highly conserved among bacteria, yeast and plants as well as vertebrates. Northern blot analysis revealed abundant expression of approximately 1 kb mRNA in testis, liver, brain and kidney with lower levels of the expression in thymus, spleen, heart and stomach. The mThy28 gene spans at least 7 kb of genomic DNA, and contains eight exons and seven introns. The 5'-flanking region of the mThy28 gene does not contain a typical TATA box, but contains a putative CCAAT box and presumably multiple transcription initiation sites. Potential Sp1, GATA-1, -2, -3, AP-1, and p300 binding sites were found in the 5'-flanking region of the mThy28 gene. The gene was mapped to mouse chromosome 9.

3T3 Cells↗

PubMed2002

Requirement of c-Jun N terminal kinase and P38 mitogen-activated protein kinase for anti-IgM-induced reduction in mitochondrial membrane potential in CH31 B lymphoma cells.

CH31 cells have been used for analysis of B cell tolerance, since engagement of membrane immunoglobulin (mIg) results in loss in mitochondrial membrane potential (DeltaPsim), followed by cell death. We have reported that the dominant-negative (dn) form of c-Jun N-terminal kinase (JNK) substantially prevented a loss of DeltaPsim at 24 h, with partial protection around 48 h after anti-IgM stimulation. In this study, we demonstrate that anti-IgM induced a sustained activation of p38 mitogen-activated protein (MAP) kinase. The p38MAP kinase inhibitor SB203580 substantially prevented loss of DeltaPsim at 14 h, with partial prevention (18-24 h) after anti-IgM stimulation. The dnJNK1-mediated prevention of anti-IgM-induced mitochondrial dissipation was enhanced by SB203580 at 42 h, but not 24 h, after stimulation, suggesting that activation of either p38 MAP kinase or JNK may be sufficient for the initiation of early phase of anti-IgM-induced loss of DeltaPsim while both may be necessary in the late phase.

Amino Acid Chloromethyl Ketones↗

PubMed2002

Oral administration of interferon-beta suppresses experimental autoimmune uveoretinitis.

BACKGROUND: The oral administration of type I interferons (IFNs) have been reported to reduce severity of inflammation in several animal models of autoimmune disease. This study examined whether oral administration of IFN-beta is capable of modulating inflammation in experimental autoimmune uveoretinitis (EAU). METHODS: EAU was induced in rats by immunization with interphotoreceptor retinoid-binding protein (IRBP) emulsified in complete Freund's adjuvant. Rats were treated with either varying doses (10(2), 10(3), 10(4) or 10(5)IU) of mouse recombinant IFN-beta or phosphate-buffered saline for control, via direct oropharyngeal application once a day for 28 days starting 7 days before IRBP immunization. Intraocular inflammation was assessed by slit-lamp biomicroscopy and histopathological examination. Spleen cell proliferation response and cytokine production under IRBP stimulation were assessed. Spleen cell subpopulations were also measured. RESULTS: IFN-beta at doses of either 10(4) or 10(5) IU significantly reduced both the clinical and histopathological severity of EAU. Spleen cell proliferation and IFN-gamma production from rats treated with 10(4) IU IFN-beta were significantly decreased compared with controls. Furthermore, the proportion of both NK cells and NKT cells in the spleen of rats treated with IFN-beta was increased compared with controls. CONCLUSION: These results suggest that the oral administration of IFN-beta reduces inflammation in IRBP-mediated EAU and that the mechanism of this action may involve NK cells and NKT cells.

Administration, Oral↗

PubMed2002

Combined stimulation with interferon alpha and retinoic acid synergistically inhibits proliferation of the glioblastoma cell line GB12.

Since malignant glioma displays moderate resistance to conventional therapy, a new treatment modality is needed to improve the outcome of patients with these tumors. In this study, we examined whether combination stimulation with interferon alpha (IFN-alpha) and retinoic acid (RA) affected proliferation of the glioblastoma cell line GB 12 in vitro. Stimulation with IFN-alpha alone inhibited the GB 12 cell proliferation in a dose/time-dependent fashion, as assessed by WST-1 assay and uptake of 3H-thymidine, while RA limited it only slightly. The anti-proliferative action of IFN-alpha against glioblastoma cells was enhanced by the addition of RA. The IFN-alpha/RA combination also induced apoptosis in a substantial portion of the cells, compared with either reagent alone. Bcl-2 family proteins, regulating apoptosis, were altered by these stimuli: Bcl-2 was down-regulated, while Bax-alpha was up-regulated, especially by the combination. These findings suggest that the IFN-alpha/RA combination would synergistically affect glioblastoma cell growth, probably through apoptosis induction as well as a decreased cellular DNA synthesis.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

Type I interferons as immunoregulatory molecules; implications for therapy in experimental autoimmune uveoretinitis.

Clinical trials have shown that the type I interferon (IFN)-alpha/beta have some beneficial effects on organ-specific autoimmune diseases, such as Behcet's diseases and multiple sclerosis, although the precise mechanisms remain largely unresolved. T helper cells 1 (Th1)-mediated autoimmune responses are involved in the initiation and/or progression of human uveitis, such as Behcet's disease. The animal model of experimental autoimmune uveoretinitis (EAU), characterized by a monophasic clinical course, has contributed to the understanding of the pathogenesis of human uveitis. Th1 producing IFN-gamma induce EAU development, while Th2 producing IL-4/IL-10 prevent the disease. However, depending on the cytokine milieu, the pro-inflammatory cytokine IFN-gamma may attenuate the autoimmune responses and anti-inflammatory cytokine IL-4 exacerbates it. Chemokines also play a crucial role in EAU development, which might be resolved by Th2-mediated immune responses. The administration of IFN-alpha/beta prevents EAU development, accompanied by a diminished production of IFN-gamma/IL-10. Interestingly, however, IFN-alpha/beta also have some beneficial effects on patients with Th2-like phenotype in addition to Th1-like phenotypes. Thus, the immuno-modulatory action of IFN-alpha/beta may be dependent on the context of cytokine combination and/or their concentrations.

Animals↗

PubMedDate not supplied

Cerivastatin-induced apoptosis of human aortic smooth muscle cells through partial inhibition of basal activation of extracellular signal-regulated kinases.

BACKGROUND: The beneficial effects of cerivastatin including hypolipidemic properties have been demonstrated to involve nonlipid as well as lipid mechanisms. In the present study, we examined the mechanisms underlying cerivastatin-induced growth inhibition of human aortic smooth muscle (ASM) cells. METHODS: Human ASM cells were cultured in 96-well plates with or without cerivastatin in the presence or absence of mitogen-activated protein (MAP) kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase MEK1/MEK 2 inhibitor PD98059. Cell growth was assessed by colorimetric quantitation of NADH, and cell viability was determined by trypan blue dye exclusion method. The induction of apoptosis was determined by propidium iodide (PI) staining method using flow cytometer. The activation of ERKs or c-Jun N-terminal kinases (JNKs) was determined by Western blotting using antibodies (Abs) specific for phospho-ERKs or phospho-JNKs. RESULTS: Treatment of the ASM cells with cerivastatin prevented cell growth in a concentration-dependent manner through at least induction of apoptosis. The cerivastatin-induced apoptosis was reversed by coincubation with isoprenoid [mevalonate, geranylgeranyl pyrophosphate (GGPP), and farnesyl pyrophosphate (FPP)] suggesting a role for isoprenoid in the cerivastatin-induced apoptosis. The cerivastatin cooperated with a MEK1/MEK2 inhibitor PD98059 to induce apoptosis, which appeared to correlate with down-regulation of ERK activation (phospho-ERKs expression) induced by the combination. CONCLUSION: Cerivastatin-induced blockade of ERK activation in ASM cells might result in growth inhibition including apoptosis, which might explain some aspects of the beneficial effects of cerivastatin on coronary artery disease.

Aorta↗

PubMedDate not supplied

Induction of differential T-cell epitope by plain- and liposome-coupled antigen.

The T-cell receptors of CD4(+) T lymphocytes recognize immunogenic peptide sequences bound within the groove of MHC class II molecules, and the peptides that bind to these molecules are known to share common structural motifs. For example, OVA(323-339), an I-A(d)-binding peptide, involves a motif of the I-A(d) peptide-binding groove. In the present study, OVA peptides of up to 26-mer were sequentially synthesized and screened, and two additional I-A(d) binding OVA peptides, OVA(20-43) and OVA(264-286), were found to stimulate CD4(+) T cells of OVA-immune BALB/c mice. OVA(20-43) involved structural motifs of the I-A(d) peptide-binding groove, while OVA(264-286) did not. The ability of these three I-A(d) binding OVA peptides to induce antigen-specific cytokine production was compared among CD4(+) T cells of mice immunized either with alum-adsorbed OVA (OVA-alum) or OVA chemically coupled to the surface of liposome (OVA-liposome). CD4(+) T cells of mice immunized with OVA-alum produced more cytokines when stimulated with OVA(264-286) than with OVA(323-339), while CD4(+) T cells of mice immunized with OVA-liposome conjugates produced more cytokines when stimulated with OVA(323-339) than with OVA(264-286). OVA(20-43) induced production of comparable levels of cytokines in mice immunized either with OVA-alum or OVA-liposome. Confocal laser scanning microscopic analysis demonstrated that chemically coupled OVA and liposomes were colocalized in APCs until OVA received processing. Three-dimensional structural analysis demonstrated that both OVA(264-286) and OVA(323-339) were present on the surface of OVA, but OVA(20-43) was not. These results suggested that the chemical coupling of OVA to liposome affected antigen processing in APCs and thus resulted in the induction of differential T-cell epitopes as compared with those induced by plain OVA.

Amino Acid Sequence↗

PubMedDate not supplied

Retrovirus-mediated transduction of TRAIL and chemotherapeutic agents co-operatively induce apoptotic cell death in both sarcoma and myeloma cells.

BACKGROUND: Resistance to multiple chemotherapeutic agents results from a variety of factors including a lack of apoptosis in tumor cells. To induce apoptosis in two types of tumor cells, RPMI-8226 and MG-63, a combination of chemotherapeutic agents and retroviral transduction of TRAIL was employed. MATERIALS AND METHODS: Both TRAIL-sensitive 8226 and -resistant MG-63 cells were pretreated with the anti-tumor agent doxorubicin or cisplatin for 24 hours, washed and then exposed to retroviral transduction with TRAIL for a further 24 hours, followed by assay for cell survival using a WST-8 kit. RESULTS: Doxorubicin or cisplatin sensitized both RPMI-8226 and MG-63 cells to TRAIL-induced death in a synergistic manner. This combined treatment was also effective in the MG-63 cells overexpressing Bcl-xL, which are resistant to multiple chemotherapeutic agents. CONCLUSION: A retroviral transduction of TRAIL in conjunction with anti-tumor agents could provide a new treatment modality for the treatment of patients with multiple-drug resistance.

Antineoplastic Agents↗