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Biomedical subjects

H Bando

Publications and source records attributed to H Bando.

At least 19 recordsLinked to original sources

Different features of angiogenesis between ovarian and breast carcinoma.

Angiogenesis assessed by immunohistochemical staining for endothelial cells has been widely accepted as an independent prognostic factor in human breast carcinoma. However, the clinicopathologic significance of angiogenesis is still being argued in ovarian carcinoma. Therefore, we retrospectively analyzed the clinicopathologic significance of angiogenesis in ovarian carcinoma compared with that in breast carcinoma. After vessels were stained with CD34-monoclonal antibody, the areas with the highest number of intratumoral microvessels were assessed in a 200x field in 42 ovarian carcinoma and 41 breast carcinoma. Intratumoral microvessel density (IMD) in ovarian carcinoma was significantly lower than that in breast carcinoma. Further, the difference of IMD from tumor to tumor in ovarian carcinoma was smaller than that in breast carcinoma. IMD was correlated with tumor grade, but not with other clinicopathologic variables in ovarian carcinoma. Although the patients with high-IMD tumor revealed a poorer prognosis than those with low-IMD tumor in breast carcinoma, IMD had no influential effects on the survival of the patients with ovarian carcinoma. Our comparative analysis of IMD in ovarian carcinoma with that in breast carcinoma indicates that angiogenesis may play an important role in the transient of ovarian neoplasms, but not in the progression of ovarian carcinomas, and that the biological roles of angiogenesis might be different, depending on histologic subtype.

Adult↗

Interleukin (IL-)15 has less activity than IL-2 to promote type 2 cytokine predominance in tumour-associated mononuclear cells from lung cancer patients.

Deviation of type 1/type 2 cytokine balance to type 2 predominance may contribute to tumour progression. We investigated effect of interleukin (IL-)15 on modulation of type 1/type 2 balance in addition to non-major histo-compatibility complex (MHC)-restricted killer induction in the tumour-growing site. IL-15 induced significant killer activity in mononuclear cells (MNC) in malignant pleural effusion as well as those in peripheral blood. Pleural MNC produced more IFN-gamma (type 1 cytokine) by incubation with IL-15 or IL-2 than blood MNC. Moreover, IL-4 and IL-5 (type 2 cytokines) production by pleural MNC were observed only by incubation with IL-2, but not with IL-15. These observations suggest that IL-15 has a potent activity to restore type 1/type 2 balance in addition to killer induction in tumour-growing site.

Adult↗

Aromatase and aromatase inhibitors.

Aromatase inhibition provides both paracrine/intracrine and endocrine treatment. Recent accumulated data clarified that 3rd generation aromatase inhibitors potently suppress intratumoral estrogen synthesis particularly in postmenopausal patients. In the 2nd-line treatment for metastatic breast cancer patients, aromatase inhibitors achieved results antitumor activity at least equal to and sometimes better than that of tamoxifen. In the first-line treatment for metastatic breast cancer patients, a recent pivotal study clearly demonstrated that aromatase inhibitor was superior to tamoxifen. Based upon these results, various adjuvant trials which compare aromatase inhibitors with tamoxifen and attempt to determine optimal combination therapies and treatment periods with aromatase inhibitors are currently being conducted. In addition, preliminary studies conducted in neoadjuvant setting indicated that aromatase inhibitors showed an extremely high response rate, which predicts a future paradigm, that neoadjuvant therapy using aromatase inhibitors singly or in combination may become standard for hormone-responsive and post-menopausal breast cancer patients.

Anastrozole↗

Tandem repetition of baculovirus ie1 promoter results in upregulation of transcription.

In order to improve a virus-independent gene expression system in insect cells, the effect of the repetition of the promoter sequence of a baculovirus immediate early gene, BmNPV ie1, on the gene expression activity was examined. Tandem repetition of ie1 promoter resulted in about a 4-fold increase of the reporter gene expression activity. Primer extension analysis revealed that the repetition increased not only the amount of transcripts (4 to 5-times) but also the number of sites of transcription initiation (at least 3 extra initiation sites). A mutational experiment demonstrated the involvement of independent cis-acting elements in these two different promoter-enhancing effects.

Animals↗

Vascular endothelial growth factor: its prognostic, predictive, and therapeutic implications.

Since the discovery that cancer development requires the growth of new blood vessels, many investigations have revealed the key molecules in the regulation of new vessel formation. One of the most important of these molecules is vascular endothelial growth factor (VEGF)--an endothelial-cell-specific mitogen and survival factor. VEGF also causes increased vascular permeability and recruits progenitor endothelial cells from the bone marrow. Clinical observations have confirmed that VEGF status is closely associated with the extent of neovascularisation and prognosis in many solid tumours. VEGF status is predictive of resistance to various treatments, including radiotherapy, chemotherapy, and endocrine therapy. Preliminary results also indicate that anti-VEGF treatment suppresses cancer progression without serious toxic effects. Various approaches for the control of cancers involving inhibition of the activity of VEGF are currently being investigated. This review considers the clinical implications of VEGF, particularly its prognostic, predictive, and therapeutic value.

Endothelial Growth Factors↗

Chemical studies on antioxidant mechanism of curcumin: analysis of oxidative coupling products from curcumin and linoleate.

As a part of a research project on the antioxidant mechanism of natural phenolics in food components, curcumin, a turmeric antioxidant, was investigated in the presence of ethyl linoleate as one of the polyunsaturated lipids. During the antioxidation process, curcumin reacted with four types of linoleate peroxyl radicals. Six reaction products were observed in the reaction and subsequently isolated. Their structures were determined by physical techniques, revealing that they have novel tricyclic structures, including a peroxyl linkage. On the basis of the formation pathway for their chemical structures, an antioxidant mechanism of curcumin in polyunsaturated lipids was proposed, which consisted of an oxidative coupling reaction at the 3'-position of the curcumin with the lipid and a subsequent intramolecular Diels--Alder reaction.

Antioxidants↗

Thermal stability and enzymatic activity of a smaller lysozyme from silk moth (Bombyx mori).

Bombyx mori lysozyme is 10 amino acids shorter than hen egg-white lysozyme, which is a typical c-type lysozyme. It was expressed by using the methylotrophic yeast Pichia pastoris. The thermal stability and the enzymatic activity of the Bombyx mori lysozyme were estimated and compared with those of human and hen egg-white lysozymes. The denaturation temperature was 17-26 degrees C lower than those of human and hen egg-white lysozymes. Further, the enthalpy change and the heat capacity change for unfolding were smaller than those of human lysozyme. It was also confirmed that the stability against guanidine hydrochloride was lower than those of the other two lysozymes. The enzymatic activity toward a simple synthetic substrate was measured and compared with those of human and hen egg-white lysozymes. The B-F binding mode was obviously dominant, although the A-E binding mode was preferred in human and hen egg-white lysozymes.

Acetylglucosamine↗

Construction of an expression system of insect lysozyme lacking thermal stability: the effect of selection of signal sequence on level of expression in the Pichia pastoris expression system.

Expression systems of human and silkworm lysozymes were constructed using the methylotrophic yeast Pichia pastoris as a host. The leader sequence and its prepro peptide of alpha-factor (a peptide pheromone derived from yeast) and the native signal sequences of these lysozymes, were used as secretion signals. When the alpha-factor leader is used as the signal sequence, human lysozyme is secreted at a much higher level than is silkworm lysozyme. On the other hand, silkworm lysozyme, when its native signal is used, is secreted more efficiently than human lysozyme. Therefore, we expected that human lysozyme cDNA with a silkworm native signal would be secreted more efficiently than human lysozyme with its native signal. However, its level of expression was not increased. This result indicates that the native signal of silkworm lysozyme does not promote the secretion of the lysozyme, but rather alpha-factor leader inhibits the secretion. Silkworm lysozyme with the alpha-factor leader is so unstable that it could be easily attacked by some proteases and our findings suggest that the level of expression of heterologous protein with signal peptides and its stability are greatly affected by the selection of the appropriate secretion signal sequence.

Amino Acid Sequence↗

Genome organization of the densovirus from Bombyx mori (BmDNV-1) and enzyme activity of its capsid.

Bombyx mori densovirus (BmDNV-1), on the basis of the previously reported genome sequence, constitutes by itself a separate genus (Iteravirus) within the Densovirinae subfamily of parvoviruses. Inconsistencies in the genome organization, however, necessitated its reassessment. The genome sequence of new clones was determined and resulted in a completely different genome organization. The corrected sequence also contained conserved sequence motifs found in other parvoviruses. Some amino acids in the highly conserved domain in the unique region of VP1 were shared by critical amino acids in the catalytic site and Ca(2+)-binding loop of secreted phospholipase A2, such as from snake and bee venoms. Expression of this domain and determination of enzyme activity demonstrated that capsids have a phospholipase A2 activity thus far unknown to occur in viruses. This viral phospholipase A2, which is required shortly after entry into the cell, showed a substrate preference for phosphatidylethanolamine and phosphatidylcholine over phosphatidylinositol.

Amino Acid Sequence↗

Expression of multidrug resistance-related transporters in human breast carcinoma.

The expression levels of mRNA for multidrug resistance 1 (MDR1) gene, multidrug resistance protein 1 (MRP1), lung resistance-related protein (LRP) and breast cancer resistance protein (BCRP), which confer multidrug resistance in vitro, were examined in 43 untreated breast carcinoma patients, of whom 38 subsequently received doxorubicin-based chemotherapy after surgery, in order to elucidate the roles of these genes in drug resistance in vivo. The mRNA levels were determined using a semi-quantitative reverse-transcription polymerase chain reaction method in breast carcinoma tissues including at least 80% carcinoma cells. The expression level of BCRP gene was low and did not vary markedly in comparison with that of MDR1, MRP1 or LRP gene. The expressions of MDR1 and MRP1 genes were correlated with each other, but the expression of BCRP or LRP gene did not correlate with that of other genes. These four gene expressions were independent of age, TNM categories and the status of progesterone or estrogen receptor. The expression levels of these four genes were not related to the relapse or prognosis of the 38 patients treated with doxorubicin-based chemotherapy. P-glycoprotein (P-gp) / MDR1, MRP1 and LRP may play more important roles than BCRP in chemotherapy of human breast carcinoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[A trial with single-agent vinorelbine in taxane-resistant non-small cell lung cancer].

It is reported that the single-agent administration of vinorelbine (VNR) is improper in salvage therapy for non-small cell lung cancer. However, there are few reports on its use as second line in taxane-containing chemotherapy. We used single-agent VNR administration for nine cases of taxane-resistant non-small cell lung cancer, and an antitumor effect was seen in four cases. We present three of these cases. A factor for the high response rate is considered to be that vinca alkaloid is not used as a pre-treatment. Moreover, VNR may be effective even if there is a gene mutation for beta tubulin, which causes taxane resistance.

Adult↗

[Efficacy of weekly docetaxel therapy for advanced or recurrent breast cancer].

To evaluate the safety and efficacy of weekly docetaxel (weekly TXT) in cases of advanced or recurrent breast cancer, 31 patients were enrolled in this pilot study of weekly TXT given at 25 mg/m2/w. Each cycle consisted of 3 weeks of therapy followed by a 1-week treatment break in an outpatient setting. Patients received a median of 15 infusions with a median cumulative dose of 680 mg. The median time to treatment failure was 8 months. The overall response rate was 32.3%, and 22.6% of patients had stable disease for at least 6 months. The response rate was consistent regardless of prior chemotherapy with anthracycline. There was no grade 3 or 4 toxicity, and the regimen was generally well tolerated. Although 37.5% of patients had grade 1 or 2 nail change, myelosuppression, fatigue, nausea, vomiting and fluid retention were mild. Weekly TXT seems to be an effective and feasible treatment for advanced or recurrent breast cancer patients.

Adult↗

[Combination chemotherapy of carboplatin and docetaxel for advanced non-small cell lung cancer (NSCLC)].

Since mid-1997, we have treated 60 patients with advanced NSCLC with carboplatin (CBDCA) plus docetaxel (TXT). CBDCA (300-400 mg/m2) and TXT (60 mg/m2) were given on day 1 every 3 weeks. The mean treatment cycle was 2.3 +/- 1.4 (range 1-7). Fifty-four patients had measurable tumors, of whom 2 patients achieved a complete response and 19 patients achieved a partial response (37.0%, 95% CI: 24.3-51.3%) (Ad 12/29, Sq 7/23, Lar 1/2). Median survival time was 12.8 months and 1 year survival was 53.6%. AUC of CBDCA was not related to response (AUC of responders and non-responders was 3.29). Myelosuppression was moderate (WBC 2,284 mm3, range 800-4,700, PLT 16.4 x 10(4) mm3, range 6.6-41.5 x 10(4), Hb 10.9 g/dl, range 6.4-15.8). Leukocytopenia was related to AUC of CBDCA (R2 = 0.1093) but thrombocytopenia was not related to AUC of CBDCA (R2 = 0.0553). Gastrointestinal toxicity was mild (grade 0-1: 57%, grade 2: 35%, grade 3: 8%, grade 4: 0%). Treatment with CBDCA plus TXT combination is safe and effective in patients with NSCLC.

Adult↗

Soluble CD154 in rheumatoid arthritis: elevated plasma levels in cases with vasculitis.

OBJECTIVE: To determine the levels of soluble CD154 (sCD154) in the plasma of patients with rheumatoid arthritis (RA) and rheumatoid vasculitis (RV). and to examine the relationship between the levels of sCD154 in plasma and the clinical variables. METHODS: Levels of sCD154 were quantified in 39 plasma samples from patients with RA, including 9 patients who were also diagnosed with RV, and compared with those of 20 healthy subjects. An ELISA was established and specificity of the ELISA was tested by control ELISA using isotype-matched IgG and preabsorption assay. The titers of IgM and IgG rheumatoid factor (IgM-RF, IgG-RF) for each patient were determined simultaneously, and values of other laboratory variables were also determined. RESULTS: Levels of sCD 154 in plasma were higher in patients with RA than in the healthy subjects (p < 0.02). Compared with RA patients without vasculitis, patients with RV had significantly higher levels of sCD154 in their plasma (p < 0.001). Control ELISA and absorption assay of sCD154 indicated that our ELISA system was capable of measuring plasma sCD154 in RA patients. Levels of sCD154 in RA plasma correlated significantly with both IgM-RF and IgG-RF titers (r = 0.64 and 0.61, respectively, both p < 0.001). The levels of sCD154 decreased after commencement of treatment for vasculitis in cases with RV. CONCLUSION: We identified the presence of sCD154 in RA plasma, with especially high levels in cases with vasculitis. Correlation between sCD154 and RF titers indicates the CD154-CD40 pathway is likely related to pathogenic RF production.

Adult↗

The predictive value of angiogenesis for adjuvant therapy in breast cancer.

Recent accumulated data have indicated that angiogenesis is a promising indicator to predict prognosis and response to treatment. In breast cancer, microvessel density (MVD), a semi-quantitative marker of neovascularization grade, has been suggested to provide independent prognostic value. In addition, the expression of both vascular endothelial growth factor (VEGF)and thymidine phosphorylase (TP), two angiogenesis regulatory molecules, were found to be closely associated with MVD, and with the effect of treatments. In particular, VEGF expression seems to be a phenotype resistant to endocrine therapy, whereas TP expression decreases sensitivity to chemotherapy containing fluorouracil. This review summarizes the current topics regarding the prognostic and predictive value of angiogenesis in primary breast cancer, and we discuss future applications of antiangiogenesis treatments in an adjuvant setting.

Angiogenesis Inhibitors↗

N-glycosylation contributes to the limited cross-reactivity between hemagglutinin neuraminidase proteins of human parainfluenza virus type 4A and 4B.

cDNAs encoding human parainfluenza virus type 4B (hPIV-4B) hemagglutinin neuraminidase (HN) protein were cloned and the nucleotide sequences were determined. A high degree of identity (81.4%) was observed between the nucleotide sequences of hPIV-4A and -4B HN proteins, and an 87.3% identity was found between the deduced amino acid sequences. This degree of identity is considered to be greater than immunological similarity between hPIV-4A and -4B HN proteins determined using monoclonal antibodies. To elucidate the causes of the antigenic difference between HN proteins of hPIV-4A and -4B, we constructed three cDNAs of hPIV-4B HN whose potential N-glycosylation sites were partially or completely the same as in hPIV-4A HN cDNA. We compared the antigenicity of the expressed wild-type and mutant proteins, and found that the antigenicities of the mutant hPIV-4B HN proteins were more similar to the hPIV-4A HN protein than to the non-mutant hPIV-4B HN protein. This study indicated that the antigenic diversity between hPIV-4A and -4B was partly caused by deletion or creation of glycosylation sites, showing that the point mutations resulting in deletion or creation of glycosylation sites is one of the initial steps leading to the division of virus into subtypes.

Amino Acid Sequence↗

Analysis of proteins encoded in the bipartite genome of a new type of parvo-like virus isolated from silkworm - structural protein with DNA polymerase motif.

Bombyx mori densonucleosis virus type 2 (BmDNV-2) is a small, spherical virus containing two complementary single-stranded linear DNA molecules (VD1, VD2). BmDNV-2 is a new type of virus with a unique, yet unspecified replication mechanism which is different from that of parvoviruses (Bando, H., Choi, H., Ito, Y., Nakagaki, M. , Kawase, S., 1992. Structural analysis on the single-stranded genomic DNAs of the virus newly isolated from silkworm: the DNA molecules share a common terminal sequence, Arch. Virol. 124, 187-193; Bando, H., Hayakawa, T., Asano, S., Sahara, K., Nakagaki, M. , Iizuka, T., 1995. Analysis of the genetic information of a DNA segment of a new virus from silkworm, Arch. Virol., 140, 1147-1155; Hayakawa, T., Asano, S., Sahara, K., Iizuka, T., Bando, H., 1997. Detection of replicative intermediate with closed terminus of Bombyx densonucleosis virus. Arch. Virol. 142, 1-7). Recent analyses on the genomic information of BmDNV-2 identified open reading frames which code for three tentative nonstructural proteins and four (VP1 to 4) of the six known structural proteins (Bando, H., Hayakawa, T., Asano, S., Sahara, K., Nakagaki, M., Iizuka, T., 1995. Analysis of the genetic information of a DNA segment of a new virus from silkworm, Arch. Virol., 140, 1147-1155; Nakagaki et al., in preparation). In this report we demonstrate that the two largest ORFs, VD1-ORF1 and VD2-ORF1, code for the two remaining structural proteins. In addition, computer-assisted analysis revealed that the structural protein encoded in VD1-ORF1 contains sequences conserved among various DNA polymerases, and showed an evolutionary relationship with the DNA polymerases involved in protein-primed replication.

Amino Acid Motifs↗