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Biomedical subjects

S Tsunoda

Publications and source records attributed to S Tsunoda.

At least 109 records · Page 6Linked to original sources
PubMed1996

In vivo anti-tumor efficacy of polyethylene glycol-modified tumor necrosis factor-alpha against tumor necrosis factor-resistant tumors.

We previously reported that the optimally PEGylated tumor necrosis factor-alpha (MPEG-TNF-alpha), in which 56% of the TNF-alpha-lysine amino groups were coupled with polyethylene glycol (PEG), had about 100-fold greater anti-tumor effect than native TNF-alpha. Here, we assessed the usefulness of MPEG-TNF-alpha as a systemic anti-tumor therapeutic drug, using B16-BL6 melanoma and colon-26 adenocarcinoma, which have been reported to be resistant to TNF-alpha in vivo, as compared with Meth-A fibrosarcoma. MPEG-TNF-alpha markedly inhibited the growth of both tumors without causing any TNF-alpha-mediated side-effects, whereas native TNF-alpha had no anti-tumor effects and caused adverse side-effects. In addition, MPEG-TNF-alpha drastically inhibited the metastatic colony formation of B16-BL6 melanoma. MPEG-TNF-alpha may, thus, be a potential systemic anti-tumor therapeutic agent.

Adenocarcinoma↗
PubMed1996

Tumor cell proliferation and apoptosis associated with the Gamma Knife effect.

In this study, the expression of proliferating-cell nuclear antigen (PCNA) and Bcl-2 protein was examined in neurinomas, meningiomas, pituitary adenomas, and malignant lymphomas before treatment with Gamma Knife radiosurgery. Tumor volume was rapidly reduced by radiosurgery in all malignant lymphomas and in some benign tumors. The latter had been characterized by strong positive immunohistochemical staining for PCNA and Bcl-2. Radiation-induced apoptosis is thought to contribute to the low-dose effects of Gamma Knife radiosurgery. A population with a large proportion of proliferating cells may be susceptible to the induction of apoptosis, and the presence of Bcl-2 may not suppress this Gamma Knife effect.

Apoptosis↗
PubMed1996

Influence of unsuccessful lactation on subsequent reproduction and age of onset of mammary tumours in SHN mice.

SHN/Mei female mice were classified into 8 groups according to their lactation records in 3 litters from group 1 with successful lactation in all 3 litters to group 8, which failed to lactate in all litters, and the differences in reproductive parameters and the age of onset of mammary tumours was compared between group 1 and the other groups. Pup growth was retarded and the age of onset of mammary tumours were shortened by the experience of the unsuccessful lactation; both parameters were largely affected by the proliferation and differentiation of mammary glands, which are modulated by the unsuccessful lactation. The unsuccessful lactation did not affect consistently litter size or rearing rate.

Age of Onset↗
PubMed1996

[Interrelationship of reflux bile acid concentration and the gastric mucosal change with reference to the pathophysiologic significance of taurine conjugated deoxycholic acid and chenodeoxycholic acid].

Since chronic gastritis is adversely affected by reflux bile acids, we are interested in which of these bile acids cause the most damage to the gastric mucosa as ulcerogenic factors in the stomach. We examined 34 patients suffering from the peptic ulcers, and have assumed that taurine conjugated deoxycholic acid (TDC) and chenodeoxycholic acid (TCDC) may act as the mst ulcerogenic factors. Moreover TCDC was suggested to be associated with the cystic dilatation of the gastric gland. It was also suggested that TDC is involved in the increased frequency of intestinal metaplasia as a factor backgrounding cancer.

Adult↗
PubMed1996

The mRNA expression of neurocan, a brain-specific chondroitin sulfate proteoglycan, in neoplastic mammary glands in mice.

In the experiment of mouse transforming growth factor alpha (TGF alpha) gene expression in mammary tumors, various sizes of amplified products by reverse transcriptase-polymerase chain reaction (RT-PCR) using mouse TGF alpha primers were detected in addition to a predicted size in four strains of mice. During the further analysis of these RT-PCR products in mouse mammary tumors, the transcript of neurocan gene was detected in the mammary tumor from SHN mice by the cloning and nucleotide sequence analysis after RT-PCR reaction using mouse TGF alpha primers. The 5'-nucleotide sequence of sequential 246bp in the amplified cDNA of 527bp was completely identical to a middle part of mouse neurocan cDNA sequence, one of the chondroitin-sulfate proteoglycan expressed in the nervous tissue.

Animals↗
PubMed1996

Sequential occurrence of hepatocellular carcinoma following Waldenström's macroglobulinemia: the pathogenetic role of chronic liver disease.

We report a case of sequential occurrence of hepatocellular carcinoma (HCC) following Waldenström's macroglobulinemia (WM) in the course of chronic liver disease. The diagnosis of WM was made in a 55-year-old man with a history of alcohol abuse. He developed HCC in the course of WM, and hepatitis C virus (HCV) infection was detected by enzyme-linked immunosorbent assay. Recent reports suggest that persistent HCV infection is related to the pathogenesis of B cell malignancy. Chronic liver disease may be associated with the pathogenesis of the double malignancies in the present case.

Carcinoma, Hepatocellular↗
PubMed1996

Immature teratoma in the cerebral basal ganglia of an adult.

A 19-year-old male underwent an emergent operation for a massive brain tumor in the right cerebral basal ganglia. However, brain herniation had already developed and he subsequently died. Histological examination showed the tumor consisted of immature epithelial arrangements and glandular structures, considered as immature teratoma containing choriocarcinomatous components. Such an immature teratoma arising in the cerebral basal ganglia in an adult is very rare.

Adult↗
PubMed1996

[A case of drug-induced immune hemolytic anemia during alpha-interferon therapy for renal cell carcinoma].

A Case of drug-induced immune hemolytic anemia during alpha-interferon (alpha-IFN) therapy for renal cell carcinoma is reported. A 61-year-old woman was admitted to Tochigi cancer center for the treatment of left renal cell carcinoma. She underwent left radical nephrectomy. From 7th post operative day, alpha-IFN (6 x 10(6) IU) was administered every other day. Diclofenac and indomethacin were administered for pain and high fever induced by alpha-IFN. Hemoglobinuria was first noted on 20th post operative day. Immune hemolytic anemia was suspected by blood examinations including Coombs' test, serum haptoglobin, serum LDH and serum GOT. alpha-IFN therapy and administration of diclofenac and indomethacin were discontinued and prednisolone therapy (50 mg daily) was begun. Hemoglobinuria disappeared by 5 days and laboratory data became in normal range by 3 weeks. Drug-induced immune hemolytic anemia was diagnosed by the process of laboratory data, especially of direct Coombs' test. Though drug-induced immune hemolytic anemia is a rare adverse side effect during alpha-INF therapy for renal cell carcinoma, it seemed an important complication.

Anemia, Hemolytic, Autoimmune↗
PubMed1996

Expression of costimulatory molecules in human leukemias.

In order to determine the indication of B7 (B7-1 and B7-2) molecules-mediated immuno-gene therapy for human leukemias, we investigated 94 human leukemic samples for the expression of MHC molecules required for tumor antigen-specific signals and of B7-1, B7-2, and ICAM-1 molecules required for non-specific costimulatory signals. All samples were strongly positive for MHC class I and 84% for class II antigen. B7-1, B7-2 and ICAM-1 were expressed in 5%, 22% and 16% of the total cases, respectively. Especially in 54 AML samples, B7-1 was only expressed in one case, while B7-2 was detected in as many as 15 cases (28%). We have also examined 13 human myelo/monocytic cell lines for the expression of class II and costimulatory molecules and found that significant expression of costimulatory molecules was induced in human leukemic cells by some suitable drugs, among which interferon-gamma (IFN-gamma) was the most potent inducer. Our results indicate that when the B7-mediated immuno-gene therapy was applied to human leukemias, especially to AML, B7-1 was rather preferable to B7-2 in that the latter was more widely expressed on human leukemic cells. Furthermore, since gene-transfer systems occasionally accompany serious problems, it should be taken into account that costimulatory molecules on human myelo/monocytic leukemic cells could be induced ex vivo without the introduction of exogenous genes.

Antigens, CD↗
PubMed1996

[Effects of carboplatin combination with etoposide against leukemia/lymphoma cell lines].

We studied the effects of carboplatin in combination with etoposide in human B-cell lymphoma cell lines, BALL-2, Dauji and human T-cell leukemia cell lines, CEM, HSB and MOLT-3 cells. Cells were incubated for 3 days in the presence of carboplatin and etoposide, and the combined drug and cell growth inhibition was determined by MTT assay. The effects of drug combinations at ID80 were analyzed by an improved isobologram method (Steel and Peckham). In the combination of carboplatin with etoposide, the data points fell in the envelope of additivity (additive effect) in all five cell lines. Synergistic and antagonistic effects were not observed. These findings suggest that the combination of carboplatin and etoposide are as effective as expected.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Molecular design of hybrid tumor necrosis factor-alpha III: polyethylene glycol-modified tumor necrosis factor-alpha has markedly enhanced antitumor potency due to longer plasma half-life and higher tumor accumulation.

We have reported that chemical modification of tumor necrosis factor-alpha (TNF-alpha) with polyethylene glycol (PEG) markedly increases its antitumor potency without any adverse side effects. MPEG-TNF-alpha, especially, in which 56% of the lysine amino groups of TNF-alpha are coupled with PEG, exhibits 100-fold more antitumor activity in vivo than native TNF-alpha in the Meth-A murine sarcoma model. In this study, we investigated the pharmacokinetics of PEG-modified TNF-alpha with various molecular sizes to clarify the mechanisms of the enhanced antitumor potency of MPEG-TNF-alpha. The plasma half-lives of modified TNF-alpha increased with increasing molecular size. The decreased plasma clearance of modified TNF-alpha was partially caused by the shielding effect of the proteolytic sites in TNF-alpha by the attached PEG and the decreased transport from blood to various tissues. Almost all native TNF-alpha was uniformly distributed to the kidney and reticuloendothelial system within 1 hr of an intravenous administration, and rapidly disappeared from these tissues at 3 hr. However, very little native TNF-alpha was transported into the tumor. The absolute distributed amount and distribution profile of modified TNF-alpha to tissues other than the tumor were the same as those of native TNF-alpha, whereas the plasma levels of the modified TNF-alpha were higher than plasma levels of the native TNF-alpha. The tumor distribution of modified TNF-alpha was markedly enhanced compared with native TNF-alpha and gradually increased over time. About 9-fold more MPEG-TNF-alpha was distributed to the tumor than native TNF-alpha. Thus, we found that the marked increase in the antitumor potency of PEG-modified TNF-alpha resulted from the enhanced blood residency and tumor accumulation. The antitumor effect of MPEG-TNF-alpha against sarcoma-180 other than Meth-A fibrosarcoma was also about 100 times greater than that of native TNF-alpha when systemically administered. The optimal PEGylation of TNF-alpha facilitated its antitumor potency and MPEG-TNF-alpha may be useful systemic antitumor therapeutic drug.

Animals↗
PubMed1996

Tissue factor pathway inhibitor production by human mesangial cells in culture.

Fibrin formation within the glomeruli has been observed in various forms of human and experimental glomerulonephritis and it may play an important role in progressive glomerular injury. Furthermore it has been hypothesized that glomerular fibrin deposition may occur through activation of either the intrinsic or extrinsic coagulation pathway. It has been demonstrated that a procoagulant activity (PCA) which is compatible with tissue factor is present in the glomeruli and becomes increased in human proliferative glomerulonephritis and in animal models of nephritis. Tissue factor pathway inhibitor (TFPI) regulates the extrinsic pathway of blood coagulation through its ability to inhibit tissue factor activity. TFPI is present in plasma and in platelets, and it is now thought to be produced mainly by endothelial cells. We examined whether human mesangial cells (HMC) could produce TFPI and attempted to clarify regulatory factors which affect TFPI production. Cultured HMC were used and TFPI in the cell supernatants was measured by ELISA using a specific antibody. Cultured HMC showed the production of TFPI. Immunoblot analysis revealed 40 kD protein of TFPI. The concentration of TFPI was significantly increased following the incubation with thrombin and heparin, including low molecular weight heparin, in a dose- and time-dependent manner. However, fetal calf serum, phorbol myristate acetate, lipopolysaccharide, IL-1 beta and tissue factor did not stimulate TFPI synthesis. Our data show that cultured HMC have the ability to produce TFPI which inhibits fibrin formation. It is possible that thrombin-induced enhancement of TFPI synthesis may be caused by the autoregulatory system of blood coagulation and that with heparin it may represent another anticoagulatory effect of heparin.

Anticoagulants↗
PubMed1996

Deterioration of urinary findings after tonsil stimulation in patients with IgA nephropathy.

We studied whether urinary findings are affected by stimulation of tonsils in patients with IgA nephropathy. In 62 patients with IgA nephropathy and 20 patients with other renal diseases tonsils were stimulated by an ultra short wave for 10 min. Changes in amount of urinary protein, urinary sediment, blood leucocyte count, concentrations of serum IgA and serum secretory IgA were evaluated after tonsil stimulation. Forty of 62 patients with IgA nephropathy (65%) showed deterioration of urinary findings after the stimulation compared with 6 of 20 patients with other renal diseases (30%). The deterioration was significantly more frequent in IgA nephropathy than in other renal diseases (p <0.005). Previous episodes of gross hematuria following upper respiratory tract infections had occurred in 17 of 40 patients who showed deterioration of urinary findings after tonsil stimulation (43%) as against in 4 of 22 without deterioration (18%). The level of serum secretory IgA was higher in patients who showed deterioration of urinary findings after tonsil stimulation than in those who did not show it. Though tonsil stimulation increased blood leucocyte count it did not affect the concentrations of serum IgA or secretory IgA. It is concluded that tonsil stimulation often deteriorates urinary findings in patients with IgA nephropathy; therefore chronic tonsillitis may play a part in the pathogenesis of IgA nephropathy.

Adolescent↗
PubMed1995

Direct approach to intracranial vertebral arteriovenous fistula. Case report.

A case of intracranial vertebral arteriovenous fistula is reported. The treatment of choice for this particular vascular malformation is controversial because of the difficulty of management of the intracranial portion of the lesion. We here report a case treated successfully by direct surgery. Its anatomical delineation and operative approach are discussed.

Adult↗
PubMed1995

Increased sympathetic outflow to muscles in patients with amyotrophic lateral sclerosis: a comparison with other neuromuscular patients.

We investigated the effects of muscle loss and limitation of daily activities on sympathetic outflow to muscles by measuring muscle sympathetic nerve activity (MSNA) in 12 patients with amyotrophic lateral sclerosis (ALS) as compared with other 15 neuromuscular patients (controls). The burst incidence of MSNA at rest was significantly higher in patients with ALS, even in elderly patients, compared with controls (p < 0.01). There were no differences in the level of disability, heart rate or blood pressure at rest between two groups. Blood pressure and MSNA were less changed by head-up tilting in patients with ALS compared with controls. MSNA of ALS was not correlated with the disability score, PaO2, PaCO2, forced vital capacity, the disease duration or prognosis. MSNA at rest was increased in ALS patients, regardless of the severity of muscle loss or disability. It might be suggested that autonomic motor neurons seem to become affected by the same pathologic process that kills motor neurons.

Adult↗
PubMed1995

Membranoproliferative glomerulonephritis associated with hepatitis C virus infection responsive to interferon-alpha.

A 42-year-old man with hepatitis C virus infection, cryoglobulinemia, hypocomplementemia, and nephrotic syndrome is reported. The kidney biopsy showed membranoproliferative glomerulonephritis. The patient was treated with interferon-alpha for 2 months. After the treatment, serum hepatitis C virus RNA became negative and nephrotic syndrome remitted. Repeat biopsy of the kidney revealed an improvement in renal histology. This case confirms an association between hepatitis C virus infection and membranoproliferative glomerulonephritis and the usefulness of interferon-alpha for treatment.

Adult↗
PubMed1995

Schedule-dependent interaction between paclitaxel and doxorubicin in human cancer cell lines in vitro.

The schedule-dependent interaction of paclitaxel and doxorubicin was evaluated in four human cancer cell lines. The cells were exposed simultaneously or sequentially to the two agents for 24 h, and were then incubated in drug-free medium for 4 and 3 days, respectively. The cell growth inhibitions were determined by the MTT assay. The cytotoxic interactions at the IC80 level were evaluated by the isobologram method of Steel and Peckham. In non-small cell lung cancer A549, breast cancer MCF7 and colon cancer WiDr cells, antagonistic effects were observed for the paclitaxel and doxorubicin combination on simultaneous exposure to the two agents and on sequential exposure to doxorubicin followed by paclitaxel, while additive effects were observed for the combination on sequential exposure to paclitaxel followed by doxorubicin. In ovarian cancer PA1 cells, additive effects were observed for all schedules. These findings suggest that sequential administration of paclitaxel followed by doxorubicin may be the most suitable sequence, while the simultaneous administration of the two agents and the sequential administration of doxorubicin followed by paclitaxel may result in less tumour cell kill than anticipated. Further preclinical and clinical studies are required to elucidate the relationship between paclitaxel and doxorubicin with regard to both antitumour activity and toxicity.

Antineoplastic Combined Chemotherapy Protocols↗