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H Bando

Publications and source records attributed to H Bando.

At least 37 records · Page 2Linked to original sources

[Antiangiogenesis therapy and hormone therapy--their resemblance and applications of prognostic and predictive factors].

Many new ideas to control tumor angiogenesis are now being tested in clinical trials. In considering strategies for clinical development of antiangiogenesis treatment, that of endocrine therapy might be particularly useful as a model. Endocrine therapy is a unique treatment used only for hormone-dependent tumors; however, its clinical fruits are exceptional in the entire history of cancer therapy. It is now clearly proven that long-term continuous treatment with antihormones brings a magnificent survival benefit for primary breast cancer patients. This benefit is tumor-phenotype oriented, where the hormone receptor is characterized as a potent predictive factor. Antiangiogenesis treatments seem to have several similarities with endocrine therapy, in that both treatments are cytostatic, stroma-targeting, time-dependent and less effective for large tumor burdens. A combination effect with chemotherapy is often observed with both treatments, at least in animal experiments. In a sense, anti-oncogene product therapy follows endocrine therapy in clinical development. Although antiangiogenesis treatments should be developed based on original concepts, the successful experience of endocrine therapy may provide many hints for the development of antiangiogenesis therapy.

Angiogenesis Inhibitors↗

Significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis, and survival in human breast cancer.

Tumor cells stimulate the formation of stroma that secretes various mediators pivotal for tumor growth, including growth factors, cytokines, and proteases. However, little is known about the local regulation of these soluble mediators in the human tumor microenvironment. In this study, the local expression of cytokines, chemokines, and angiogenic factors was investigated in primary breast cancer tissue. The concentrations of interleukin (IL)-1, IL-4, IL-6, IL-10, IL-12, tumor necrosis factor (TNF)-alpha, IFN-gamma, IL-8, macrophage chemoattractant protein (MCP)-1, epithelial-neutrophil activating peptide-78, vascular endothelial growth factor, and thymidine phosphorylase (TP) were measured in 151 primary breast cancer extracts by ELISA. Tumor-associated macrophages (TAMs) were also examined by immunohistochemistry with anti-CD68 antibodies. The correlation between soluble mediators and the relationship between TAM count and soluble mediators were evaluated. MCP-1 concentration was correlated significantly with the level of vascular endothelial growth factor, TP, TNF-alpha, and IL-8, which are potent angiogenic factors. IL-4 concentration was correlated significantly with IL-8 and IL-10. On the other hand, an inverse association was observed between TP and IL-12. The level of MCP-1 was associated significantly with TAM accumulation. In the immunohistochemical analysis, MCP-1 expression was observed in both infiltrating macrophages and tumor cells. Prognostic analysis revealed that high expression of MCP-1, as well as of VEGF, was a significant indicator of early relapse. These findings indicate that interaction between the immune network system and angiogenesis is important for progression of human breast cancer, and that MCP-1 may play an important role in the regulation of angiogenesis and the immune system.

Adult↗

Presence and potent immunosuppressive role of interleukin-10 in malignant pleural effusion due to lung cancer.

The presence and possible role of interleukin (IL)-10 were examined in malignant pleural effusion due to lung cancer. In 37 out of 55 cases examined, IL-10 was detectable in pleural effusion and the mean level with standard error was 62.1+/-12.1 pg/ ml. Spontaneous and lipopolysaccharide-induced production of anti-tumor cytokines such as IL-1beta and tumor necrosis factor (TNF)-alpha, by pleural macrophages, obtained from five patients with malignant pleurisy, were suppressed by IL-10. These findings suggest that IL-10 is present in the tumor-growing site and acts as a suppressive factor of local anti-tumor immunity in humans.

Aged↗

Vascular endothelial growth factor in malignant pleural effusion associated with lung cancer.

The presence of vascular endothelial growth factor (VEGF) was examined by enzyme immunoassay in 60 cytology-documented malignant pleural effusions associated with primary lung cancer and 51 other benign and malignant pleural effusions. Exudative pleural effusions contained significantly higher amounts of VEGF than transudative pleural effusions. Among exudative pleural effusions, levels of VEGF in malignant pleural effusions associated with lung cancer were significantly higher than those of benign exudative pleural effusions. There was no significant difference in pleural VEGF in patients with different histological types or clinical stages of lung cancer. Serial measurement of pleural VEGF levels was performed in six lung cancer patients treated with intrapleural instillation of recombinant interferon gamma, and reduction of pleural effusion was associated with decreasing pleural VEGF levels. These findings suggest that VEGF has a role in the accumulation of exudative pleural effusions, especially that of malignant pleural effusion associated with lung cancer.

Adenocarcinoma↗

Genome organization and mRNA structure of Periplaneta fuliginosa densovirus imply alternative splicing involvement in viral gene expression.

We determined the complete nucleotide sequence of an infectious clone of the cockroach small spherical virus (CSSV) genome. Analysis of the genome organization and the predicted viral protein sequences showed clearly that this virus should be classified as a new member of the subfamily Densovirinae, genus Densovirus, and should be designated as PfDNV. However, our data revealed some differences between the gene expression strategies used by PfDNV and other DNVs. An internal promoter, in addition to the promoter (p3) at the genome terminus, was observed at map unit 18 (p18), implying transcriptional regulation of generation of the nonstructural proteins of PfDNV. Furthermore, the structural analysis of cDNAs complementary to mRNAs from the region coding for structural proteins suggested alternative splicing and polyadenylation as means for generation of the structural proteins of PfDNV.

Alternative Splicing↗

Infrequent presence of anti-c-Myc antibodies and absence of c-Myc oncoprotein in sera from lung cancer patients.

To clarify the host immune response and explore a new serological marker of lung cancer, we examined serum c-Myc antigens and auto-antibodies against c-Myc in 68 lung cancer patients and 30 healthy volunteers using bacterially synthesized glutathione S-transferase c-Myc fusion proteins and immunoblotting. The detection rate of anti-c-Myc antibodies was 13.2% (9/68) in lung cancer patients and 3.3% (1/30) in healthy volunteers. These anti-c-Myc antibodies were directed toward exon 2 alone (4/68), exon 3 alone (1/68), and both exon 2 and exon 3 (4/68) of c-Myc. Circulating c-Myc antigen was not detected in any individuals with lung cancer and normal controls. Age, sex, performance status, histology, stage, smoking history, and prior treatment of the patients with and without anti-c-Myc antibodies were not significantly different. The low incidence of anti-c-Myc antibodies and c-Myc antigens in peripheral blood suggests that these examinations are not useful in the serological diagnosis of lung cancer.

Adult↗

Adjuvant chemotherapy with a combination of mitoxantrone, methotrexate, 5-fluorouracil for node-positive breast cancer: phase II pilot study.

A phase II pilot study was carried out on 30 patients to ascertain the toxicity and efficacy of combination chemotherapy with mitoxantrone, methotrexate, 5-fluorouracil (NMF) in the adjuvant setting for axillary lymph node-positive breast cancer. The NMF regimen was mitoxantrone 10 mg/m2, methotrexate 40 mg/m2, and 5-fluorouracil 600 mg/m2 administered i.v. on day 1, repeated every 3-4 weeks for 6 cycles. The median nadir WBC count was 2,000/microl; grade 4 leukocytopenia occurred only in 1 patient. Nausea and vomiting appeared as grade 0 and 1 severity in 26/30 patients. Alopecia was extremely mild, appeared as grade 0 and 1 in 29/30 patients. The overall and relapse-free survival rates were 67.8% and 68.4% at the 82-month follow-up, respectively. The overall survival rate in premenopausal patients was significantly better than that in postmenopausal patients (P<0.05). NMF is a well-tolerated combination regimen, suitable as adjuvant chemotherapy for node-positive breast cancer.

Adolescent↗

Theoretical analysis of the effect of cutaneous metabolism on skin permeation of parabens based on a two-layer skin diffusion/metabolism model.

The effect of cutaneous metabolism on the skin penetration of drugs was analyzed based on a two-layer skin diffusion/metabolism model. In vitro permeation studies of propylparaben and butylparaben with or without an esterase inhibitor, diisopropyl fluorophosphate (DFP), were performed. Pretreatment of the skin with DFP prolonged the lag time for the penetration of intact parabens. Additionally, DFP significantly decreased the total flux of butylparaben, but not that of propylparaben. Model analysis of the penetration profiles revealed that DFP inhibits the cutaneous metabolism without affecting any other processes. To comprehensively understand the relationships among lipophilicity, metabolic rate, and skin permeation of drugs, simulation studies were performed with newly derived equations concerning the permeability coefficient and the lag time for the penetration of both intact and metabolite forms. The analysis revealed that the lag time for the penetration of both intact and metabolite forms becomes shorter with increasing metabolic rate. As the metabolic rate of the drug increases, skin penetration of the intact form decreases whereas that of the metabolite increases. The total flux of intact and metabolite forms increases with increasing metabolic rate, being more obvious for highly lipophilic drugs. This indicates that the permeation of lipophilic compounds such as butylparaben is more highly affected by cutaneous metabolism in the viable layer because these compounds easily penetrate the stratum corneum layer. Consequently, the balance between the permeability of drug across the stratum corneum and the dermis has been implicated to impose a significant influence on the percutaneous absorption of drugs subjected to cutaneous metabolism.

Animals↗

Analysis of genetic information of an insect picorna-like virus, infectious flacherie virus of silkworm: evidence for evolutionary relationships among insect, mammalian and plant picorna(-like) viruses.

We synthesized the cDNAs of an insect picornavirus, infectious flacherie virus of silkworm (IFV), genomic RNA and inserted it into a bacterial plasmid (pUC119). The 9,650 nucleotides (nts) sequence except for the poly(A) tail was obtained from the cloned cDNAs, and the sequence integrity was confirmed by primer extension and direct RNA sequencing. The sequence has a large open reading frame (ORF) of 9,255 nts (3,085 codons) flanked by the short 5' non-coding region (156 nts) and by the rather long 3' non-coding (239 nts). The structural proteins VP3, 4, 1 and 2 were located at the N-terminus of the polyprotein in this order and were preceded by a tentative small peptide. Computer analysis identified the sequences similar to the consensus sequences of 2C (helicase?), 3C (protease), and 3D (RNA polymerase) conserved among mammalian and plant picorna(-like) viruses. In addition, the predicted genome organization of IFV was quite similar to those of picornaviruses. Further analyses of the characteristics of the genome structure and a tentative phylogenetic tree constructed on the basis of the amino acid sequence similarity emphasized the evolutionary relationships among the insect and plant viruses.

Adenoviridae↗

Comparative analysis of interleukin 15 and interleukin 2 for induction of killer activity and of type 2 cytokine production by mononuclear cells from lung cancer patients.

Interleukin (IL) 15 is a novel cytokine with IL-2-like activity. In this study, we examined the effect of IL-15 on induction of non major histocompatibility complex (MHC)-restricted killer activity and of type 2 cytokine production by peripheral blood and pleural mononuclear cells (MNCs), from 34 lung cancer patients and 20 control subjects. IL-15 induced significant killer activity in blood MNCs from lung cancer patients as well as control subjects against a small-cell lung cancer cell line (SBC-3). Effective killer induction by IL-15 was observed even in blood MNCs and pleural MNCs from the site of tumour growth in advanced lung cancer patients. IL-12 had an additive effect with a suboptimal dose of IL-15 in induction of killer activity. In the case of MNCs from lung cancer patients, IL-10 production was more prominent when cells were incubated with IL-2 than with IL-15. IL-5 production was observed in MNCs from lung cancer patients stimulated with IL-2, but not with IL-15. These observations suggest that IL-15, by virtue of its lesser induction of type 2 cytokine, may be a better candidate than IL-2 for lung cancer immunotherapy.

Adult↗

Identification of a single cytosine base insertion mutation at Arg-597 of the beta subunit of the human epithelial sodium channel in a family with Liddle's disease.

We describe a family with Liddle's disease caused by a novel mutation of the beta subunit of the human epithelial sodium channel (ENaC). A 15-year-old Japanese female was referred to our outclinic because of hypertension. The physical examination showed no abnormal findings except mild hypertension, but the laboratory data revealed low levels of plasma renin activity, plasma aldosterone and serum potassium. A comprehensive analysis of steroid hormones showed only high levels of urinary free cortisol and 17-hydroxycorticosteroids. During loading tests, blood pressure and serum potassium responded well to triamterene and slightly to spironolactone, but did not respond to dexamethasone. In addition, the normal ratio of tetrahydrocortisol plus 5alpha-tetrahydrocortisol to tetrahydrocortisone in a 24 h urinary excretion test strongly suggested a diagnosis of Liddle's disease rather than apparent mineralocorticoid excess syndrome. DNA sequence analysis of members of this family revealed a single cytosine base insertion at Arg-597 of the beta human ENaC in the proband and her mother, leading to a loss of the last 34 amino acids from the normally encoded protein as the result of a frameshift. We conclude that a de novo cytosine insertion into the final exon of the C-terminus of the beta human ENaC is responsible for Liddle's disease in this Japanese family.

Adolescent↗

Somatostatin release as measured by in vivo microdialysis: circadian variation and effect of prolonged food deprivation.

In vivo microdialysis was used to determine SRIF release from the hypothalamus in unanesthetized male rats over a period of 24 h and in rats deprived of food for 72 h, in relation to changes in plasma GH levels. Before the experiment, a microdialysis probe was inserted into the anterior pituitary gland of the rats with an indwelling right atrial cannula. Dialysates and blood samples were collected serially, after normal feeding or 72-h deprivation of food. Normal rats implanted with the microdialysis probe showed an episodical pattern of GH secretion at intervals of 3 h. SRIF was secreted in a pulsatile fashion in the dark period in a similar manner to the light period. Mean SRIF pulse amplitude and mean SRIF level were significantly increased in the dark period. There was no significant correlation between the SRIF and GH pulses in the light period. SRIF levels in dialysates obtained from fed rats and food-deprived rats showed a pulsatile pattern. Food deprivation resulted in significant increases in mean SRIF level and mean SRIF pulse amplitude. These results suggest that the existence of circadian rhythm in SRIF release and the increase in SRIF release play an important role in suppressing GH secretion during prolonged food deprivation.

Animals↗

Characterization of a cry2A gene cloned from an isolate of Bacillus thuringiensis serovar sotto.

A cry2A-type gene, designated as cry2(SKW), was cloned from Bacillus thuringiensis serovar sotto SKW01-10.2-06, and some unique features of the gene were revealed. The cry2(SKW) gene encoded a polypeptide of 635 residues with a predicted molecular mass of 71,137 Da. Cry2(SKW) had 95.4% identity with Cry2Aa in amino acid sequence and was two residues longer than Cry2Aa. Two open reading frames (ORFs), designated as orf1 and orf2, were present upstream of the cry2(SKW) and showed high homology with the corresponding ORFs in the cry2Aa operon. The Orf2 from SKW01-10.2-06 contained a region of repeated sequences. However, unlike Cry2Aa, Cry2(SKW) formed the cuboidal crystalline inclusions when the cry2(SKW) gene was expressed in an acrystalliferous B. thuringiensis strain in the absence of the upstream ORFs. Furthermore, Cry2(SKW) was less toxic to a lepidopteran species, Bombyx mori, than Cry2Aa in spite of high homology between the two proteins.

Amino Acid Sequence↗

Detection of replicative intermediate with closed terminus of Bombyx densonucleosis virus.

Two kinds of Bombyx densonucleosis virus (BmDNV), BmDNV-1 and 2, have been isolated from sericultural farms in Japan or China. These viruses are classified into the family Parvoviridae because of the small spherical virus particle containing a single-stranded linear DNA genome. Recent studies on the genome structure of these viruses suggested that BmDNV-2 was a new type of virus with unique replication mechanism, though that of BmDNV-1 was similar to parvoviruses. However, details about the replication mechanism of BmDNVs have not been reported so far. Here, in order to elucidate the difference on replication mechanism between BmDNVs and parvoviruses, we analyzed the structure of the replicative intermediate (RI) of BmDNV DNAs by PCR using specific primers designed for detection of RI with closed terminal structure (RI-CT) which is expected to be formed by replication with self-priming mechanism. PCR using the DNA from the cells infected with BmDNV-1 could detect the expected DNA fragment, showing the existence of RI-CT. On the other hand, no fragment could be amplified from the virion DNA of the BmDNVs and the DNA extracted from BmDNV-2-infected cells, respectively. These observations strongly suggested that the BmDNV-1 replicates with the "self-priming and hairpin-transfer" mechanism similar to the human parvoviruses, while BmDNV-2 does not.

Animals↗

Effects of skin metabolism on percutaneous penetration of lipophilic drugs.

Effects of skin metabolism on percutaneous penetration of drugs with high lipophilicity were studied in vitro using rat skin pretreated with and without an esterase inhibitor, diisopropyl phosphorofluoridate [also known as diisopropyl fluorophosphate (DFP)]. Without DFP, about 96% of the total penetrated amount appeared as metabolized p-hydroxybenzoic acid in the receptor fluid after application of butylparaben, whereas about 30% penetrated as intact form after application of propylparaben. On the other hand, metabolized p-hydroxybenzoic acid was not defected in the receptor fluid under pretreatment with DFP. DFP significantly decreased (p < 0.05) the total amount that penetrated after application of butylparaben, but it did not significantly affect that of propylparaben. The results indicate that skin metabolism directly affects total amount that penetrated in the case of highly lipophilic drugs, and it was found that the higher metabolic rate to hydrophilic drugs is, the greater the amount that penetrated the skin would be. Thus, when optimal prodrugs are designed for the purpose of enhancing percutaneous penetration, we propose that the bioconversion rate to parent drugs as well as the lipophilicity of prodrugs becomes an important consideration.

Animals↗

In vivo evaluation of acyclovir prodrug penetration and metabolism through rat skin using a diffusion/bioconversion model.

PURPOSE: In order to evaluate the in vivo penetration of prodrugs which undergo metabolism in skin, we analyzed the in vivo penetration profiles of acyclovir prodrugs based on a two-layer skin diffusion model in consideration of metabolic process. METHODS: Acyclovir prodrugs (e.g., valerate, isovalerate and pivarate) were used as model prodrugs and the amounts excreted in urine were measured after percutaneous application. In vivo penetration profiles were then estimated by employing a deconvolution method and the penetration of acyclovir prodrugs was analyzed using a diffusion model. Subsequently, diffusion, partitioning and metabolic parameters were compared under in vitro and in vivo conditions. RESULTS: Although total penetration amounts at the end of the experiment were similar for the three prodrugs, the ratio of intact prodrug to total penetration amount differed significantly. Moreover, the excretion and absorption profiles were also very different for each prodrug. Enzymatic hydrolysis rate constants calculated under in vivo conditions were considerably larger than those obtained in the skin homogenate and in vitro penetration experiments. CONCLUSIONS: The present skin diffusion/bioconversion model combined with computer analysis enables us to comprehensively account for diffusion, partitioning and metabolism during in vivo percutaneous absorption. Nevertheless, different enzymatic hydrolysis rate constants obtained under both in vivo and in vitro conditions demonstrate the difficulty of obtaining accurate values for in vivo enzymatic activity from related in vitro experiments.

Acyclovir↗