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Biomedical subjects

K Tazawa

Publications and source records attributed to K Tazawa.

At least 55 records · Page 3Linked to original sources
PubMed1996

Magnetic targeting of thermosensitive magnetoliposomes to mouse livers in an in situ on-line perfusion system.

We recently reported the preparation and in vitro targeting of dextran magnetite (DM)-incorporated thermosensitive liposomes, namely thermosensitive magnetoliposomes (TMs) [Viroonchatapan et al. Pharm. Res. 12 1176-1183 (1995)]. The current study was designed to determine whether these novel liposomes can be targeted to the mouse liver with the aid of an extracorporeal magnet. An on-line liver perfusion system consisting primarily of a sample injector, permanent magnets, and a fluorescence detector was established for a real-time measurement of targeting efficiency of TMs containing calcein as a fluorescent marker. Normal and reticuloendothelial system (RES)-blocked livers from mice were used for the perfusion experiments. In the RES-blocked livers, percentage holdings of TMs were 73-80% and 26-45% in the presence and absence of magnetic field, respectively, indicating an efficient targeting of TMs with a targeting advantage index (TAI) of 1.6-3.1. On the other hand, TAI in the normal livers was found to be 1.1-1.4 and less than that in the RES-blocked livers, suggesting a role of RES uptake of TMs. The effects of DM concentrations in TM suspensions on the percentage holding of TMs were shown to be minor. Liposome concentration dependence was observed for hepatic uptake of TMs, possibly because of the saturation of phagocytosis by Kupffer cells. The present results suggest that TMs would be useful in future cancer treatment by magnetic targeting combined with drug release in response to hyperthermia.

Animals↗
PubMed1996

Inhibitory effect of a traditional Chinese medicine, Juzen-taiho-to, on progressive growth of weakly malignant clone cells derived from murine fibrosarcoma.

We have investigated the inhibitory effect of oral administration of Juzen-taiho-to, a Kampo (Chinese herbal) medicine, on progressive growth of a mouse fibrosarcoma. Spontaneously regressive QR-32 tumor cells were able to grow progressively in vivo when coimplanted s.c. with a foreign body, gelatin sponge, whereas QR-32 cells alone gradually grew for over 15 days after inoculation and thereafter regressed for up to 25 days. Oral administration of Juzen-taiho-to (40 mg/day/mouse) for 7 days after inoculation of QR-32 cells with gelatin sponge resulted in significant inhibition of tumor growth and prolongation of the survival of the tumor-bearing mice. This growth-inhibitory effect of Juzen-taiho-to observed on day 25 was dose-dependent over the dose range from 4 to 40 mg/day. Treatment with Juzen-taiho-to for 7 days before tumor inoculation with gelatin sponge also significantly suppressed tumor growth examined on day 25, as did the administration of bismuth subnitrate, which is well known to induce metallothionein, an antioxidant. On the other hand, inoculation of progressed tumor cells (QRsP) resulted in growth without gelatin sponge, leading to death in syngeneic mice. Administration of Juzen-taiho-to for 7 days after inoculation of QRsP cells resulted in a decrease of the tumor growth and prolongation of the survival of mice, but the effect was less than that on the growth of QR-32 regressor tumor after coimplantation with gelatin sponge. These results suggest that the inhibitory effect of Juzen-taiho-to is partly associated with prevention of gelatin sponge-elicited progressive growth, probably mediated by endogenous factors including antioxidant substances, in addition to the augmentation of host-mediated antitumor activity.

Administration, Oral↗
PubMed1996

Asymptomatic acute poststreptococcal glomerulonephritis following upper respiratory tract infections caused by Group A streptococci.

During an observation period of 1-2 years in 2 different districts in Japan, 104 patients were found to have upper respiratory infections caused by group A streptococci. Fourty-nine of these patients were followed prospectively to determine if renal involvement would occur. Twelve patients developed transient serum complement (CH50) depression and urinary abnormality, and 2 of these developed mild hypertension. The latent period was from 1-8 weeks after the streptococcal infection. Renal biopsies of the 12 patients with "asymptomatic" of "subclinical" acute poststreptococcal glomerulonephritis (APSGN) were examined by light, immunofluorescent and electron microscopy. Glomerular lesions ranged from mild proliferative changes to the classical pathology seen in APSGN. The 12 patients were followed for 10 years. Two of them developed persistent or intermittent hematuria, and renal biopsies obtained 4 years after the initial infection revealed mesangial proliferative glomerulonephritis without IgA deposits. The remaining patients showed no abnormal findings after the acute episode. These findings suggested that glomerular involvement after group A streptococcal infection is frequent and mesangial proliferative glomerulonephritis, which was found to develop in some, may rank with IgA nephropathy as a major cause of unexplained microscopic hematuria.

Acute Disease↗
PubMed1996

Effect of hyperthermia on proliferation and deviation of carcinoembryonic antigen and squamous cell carcinoma-related antigen of human esophageal carcinoma cells in culture.

As a basic study of hyperthermia on malignant tumors, we investigated the kinetics of proliferative activity and the values of tumor markers carcinoembryonic antigen (CEA) and squamous cell carcinoma-related antigen (SCC) in a human esophageal carcinoma cell line, SGF-4, following a change of culture temperature. The temperature range allowing cultured SGF-4 cells to proliferate was from 37 degrees C to 40 degrees C. In an experiment examining the recovery of proliferative activity, no proliferative activity was observed after the cultured cells were exposed to 42 degrees C for 72 hours. The values of CEA and SCC as tumor markers were found to be increased in association with the cell damage due to the change of temperature. These markers could thus be useful as indicators for evaluations of hyperthermia therapy effectiveness.

Aged↗
PubMed1995

Preparation and characterization of dextran magnetite-incorporated thermosensitive liposomes: an on-line flow system for quantifying magnetic responsiveness.

PURPOSE: Dextran magnetite (DM)-incorporated thermosensitive liposomes, namely thermosensitive magnetoliposomes (TMs), were prepared and characterized in order to investigate their possibility for magnetic drug targeting. METHODS: TMs containing calcein were prepared at various DM concentrations by reverse-phase evaporation of dipalmitoylphosphatidylcholine (DPPC). They were evaluated for their physicochemical properties including size, DM capture, magnetite distribution within liposomes, and temperature-dependent calcein release. Moreover, a novel on-line flow apparatus with a sample injector, a coil of tubing placed in an electromagnet, and a fluorescence detector was developed for quantifying the magnetic responsiveness of TMs. This device allowed us a real-time measurement of percentage holding of TMs by magnetic field. RESULTS: Due to water-soluble property of DM, higher contents of magnetite up to 490 mg per mmol DPPC were successfully incorporated into the liposomes with DM than with conventional magnetite (Fe3O4). Thermosensitivity and lipid integrity of TMs were not influenced by inclusion of DM. Using the on-line flow system, percentage holding of TMs by magnetic field was shown to vary with several factors; it increases as the magnetic field strength increases, the fluid flow rate decreases, the magnetite content increases, and the liposome concentration increases. Typically, at 490 mg incorporated magnetite per mmol DPPC, 0.5 ml/min-fluid flow rate, and high magnetic field strength (> or = 10 kiloGauss), approximately 100% of TMs were found to be held. CONCLUSIONS: The TMs were suggested to be useful in future cancer treatment by magnetic targeting combined with drug release in response to hyperthermia.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1995

Effects of apple pectin on fecal bacterial enzymes in azoxymethane-induced rat colon carcinogenesis.

Because of the potential significance of colonic bacteria in colon carcinogenesis, we investigated the effect of pectin of different types on fecal bacterial enzymes (beta-glucuronidase, beta-glucosidase and tryptophanase) at various periods of time after feeding rats with pectin-containing diets during azoxymethane-induced colon carcinogenesis. The diet supplemented with 20% apple pectin or 20% citrus pectin decreased the multiplicity of colon tumors, and the number of tumors was significantly decreased in the group fed apple pectin. The incidence of colon tumors in the apple pectin group was lower than that in the control group. The mean tumor size was similar among the three groups. Apple pectin feeding decreased fecal beta-glucosidase and tryptophanase levels. Furthermore, a significant decrease in the activity of beta-glucuronidase was observed in the apple pectin group during the initiation phase. These findings suggest that the protective effect of pectin on colon carcinogenesis may be dependent on the type of pectin and be related to the decrease of beta-glucuronidase activity in the initiation stage of carcinogenesis.

Adenocarcinoma↗
PubMed1995

Possibility of thermosensitive magnetoliposomes as a new agent for electromagnetic induced hyperthermia.

This study examined a possibility of dextran magnetite (DM)-incorporated thermosensitive liposomes, namely thermosensitive magnetoliposomes (TMs), as a new hyperthermic agent. The temperatures of TM suspensions and cancer tumors injected with TM suspensions were efficiently elevated up to 42 degrees C by electromagnetic induced heating at a frequency of 500 kHz under both in vitro and in vivo conditions. Thus, a possibility of TMs for selective hyperthermia was demonstrated. The temperature rises obtained at various concentrations of TMs suggest that approximately 15 mg Fe/cm3 tumor volume is adequate as a therapeutic dose of TMs for efficient selective hyperthermia.

Animals↗
PubMed1995

[Identification and analysis of immune cells infiltrating into the glomerulus and interstitium in lupus nephritis].

This study was performed to investigate the role of cell-mediated immunity in lupus nephritis (LN). Frozen sections from 38 patients with LN were examined by indirect immunoalkaline-phosphatase labeling using monoclonal antibodies to identify the immune cells infiltrating into the interstitium and glomerulus. 14 patients showed minor glomerular abnormality (MGA), 9 had mesangial LN (MesLN), 12 had diffuse proliferative LN (DPLN) and 3 had membranous LN (MLN). Monocyte/macrophage and helper/inducer T cells infiltrated in the interstitium predominantly, but intraglomerular infiltration of these cells was rare. Monocyte/macrophage and suppressor/cytotoxic T cell levels were significantly higher (p < 0.05) in the interstitium in DPLN patients and monocyte/macrophage level was significantly higher (p < 0.05) in MesLN patients than in MGA patients. In the interstitium, serum creatinine level was highly correlated with infiltrations of suppressor/cytotoxic T cell, monocyte/macrophage (p < 0.01), pan T cell and total leucocyte (p < 0.05). Clinical activity score was correlated with suppressor/cytotoxic T cell (p < 0.001), monocyte/macrophage and pan T cell (p < 0.01). These results suggest that suppressor/cytotoxic T cell and and monocyte/macrophage may play an important role in the progression of lupus nephritis.

Antibodies, Monoclonal↗
PubMed1994

An in vivo study of hepatic and splenic interleukin-1 beta mRNA expression following oral PSK or LEM administration.

The effects of orally administered biological response modifiers (BRMs) in preventing postoperative micro liver metastasis of primary colorectal cancer were examined in experimental animals. The two BRMs tested were Krestin (PSK) and Lentinus edodes mycelia (LEM). In previous experiments, we found that oral administration of PSK or LEM suppressed liver metastasis and prolonged the survival period. We also found that these agents elevated the liver natural killer (NK) and liver macrophage activities. In the present study in vivo, using reverse transcriptase-polymerase chain reaction (RT-PCR), we examined whether or not the liver and spleen have cytokines which would induce NK cells and macrophages, and whether or not the liver and spleen have cytokines induced by NK cells or macrophages. We placed emphasis on the examination of interleukin (IL)-1 beta expression in the liver and spleen in vivo. Two to six hours after oral administration of PSK or LEM (1 g/kg) to mice, IL-1 beta levels in the liver and spleen rose, and they returned to their baseline levels 24 h later. These findings suggest two possibilities: (1) hepatic IL-1 beta is potentiated by these agents soon after administration, resulting in activation of liver NK cells or macrophages, or (2) these agents stimulate IL-1 beta production by liver macrophages, and the produced IL-1 beta activates liver NK cells or liver macrophages (Kupffer cells). The results of this in vivo study suggest that the potentiation of hepatic and splenic IL-1 beta by PSK and LEM is involved in the early phases of suppression of micro liver metastases of colorectal cancer.

Administration, Oral↗
PubMed1994

TNF receptor number-dependent cytotoxicity to TNF-resistant human esophageal cancer cell lines by combination with recombinant human necrosis factor and hyperthermia.

The synergistic effect of recombinant human tumor necrosis factor (rh-TNF) and hyperthermia on five established cell lines of human esophageal cancer (SGF series) was analyzed by in vitro assays. The SGF cell lines were either resistant or slightly sensitive to rh-TNF. However, they became highly sensitive to rh-TNF even at as low a concentration as 10 U/ml and dose-dependently when combined with hyperthermia (43.5 degrees C, 60 min). This result was due to synergistic effects of rh-TNF and hyperthermia, and the degree of the effect increased with the hyperthermic temperature and TNF concentration. The number of TNF receptors per cell varied widely from cell line to cell line, from 4,400 to 23,100, which did not correlate to the extent of cytotoxicity by rh-TNF alone. The degree of synergistic effect of rh-TNF and hyperthermia was evaluated quantitatively in terms of a Synergistic Index (S. I. = Predicted cell viability/Experimental cell viability): A significant correlation was found between the logarithmic S. I. and the number of TNF receptors. These findings indicated that the combination of rh-TNF and hyperthermia produced a significant antitumor effect even on the cell lines poorly sensitive to TNF in a receptor-dependent manner, although the cellular sensitivity to TNF alone was not directly correlated to the number of TNF receptors.

Drug Screening Assays, Antitumor↗
PubMed1994

[Successful treatment of advanced gastric cancer (Borrmann 1 type) with FTP chemotherapy after reduction surgery].

A 54-year-old man was diagnosed with Borr 1 type gastric cancer, located just below ECJ with some paraaortic lymph node metastase, during treatment of diabetes mellitus at another hospital. He underwent spleno-total gastrectomy for reduction. The metastatic lymph nodes of the para-aorta were not resected, so the surgery was considered palliative. We administered FTP chemotherapy (CDDP 110 mg/day 1, 5-FU 1,200 mg/day 1-5, THP-ADM 30 mg/day 1) 5 times following surgery. The metastatic lymph nodes were remarkably decreased in size by the initial treatment. The decrement was 52.4% after the initial treatment (PR). After the 4th treatment, there were no lymph nodes detected (CR). After the 5th treatment, CR continued. The PR period was considered to be 5 months, and that of CR 4 months. The patient has no renal or heart dysfunction, and no suppression of bone marrow. His quality of life is satisfactory, and he continues to work as prior to surgery. FTP chemotherapy is considered a successful regimen for postoperative chemotherapy.

Adenocarcinoma, Papillary↗
PubMed1993

[Clinicopathological evaluation of high-range hyperthermia for advanced thoracic esophageal carcinoma].

The effectiveness of high-range hyperthermia over 45 degrees C for advanced esophageal carcinoma was clinicopathologically evaluated. Fifty-eight patients with advanced thoracic esophageal carcinoma were treated with radio-chemotherapy. They were divided into two groups: group I included 32 cases, all of whom received hyperthermia (13 cases: high-range hyperthermia); group II included the other 26 cases. The patients were given 2 Gy/day for a total of 15 sessions in 3 weeks. Bleomycin and cisplatin in combination with 5-fluorouracil have been employed as chemotherapy. Hyperthermia was performed twice a week for a total of 6 sessions. Intraluminal heating was done using Japan Crescent Inc. IH-500 T (RF, 13.56 MHz), with an intraesophageal applicator and two extra-corporeal applicators on the chest and the back. Concerning local effects, the efficacy rate was 81.3% in group I (high-range: 92.9%), and 42.3% in group II. The histologic effectiveness, when Grade 2 and 3 are determined as histologically effective, were 64.3% (high range: 85.7%) and 50.0% in group I and II, respectively.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

[Experimental study on comparative efficacy of hepatic arterial injection of anticancer agent under temporary occlusion of portal vein].

To compare the efficacy of intra-hepatic arterial infusion of anti-cancer drug under temporary occlusion of portal vein, the following two experiments were performed. 1. VX2 tumor cells (about 1 x 10(5) cells) were transplanted through the superior mesenteric vein of the rabbits, after 2 weeks, 4'-0-Tetrahydropyranyl doxorubicin (2 mg/kg, 2 ml) aqueous solution (THP) was administered into hepatic artery of rabbits with metastatic VX2 liver tumor. 2. THP was injected into hepatic artery under temporary occlusion of portal branch of median left lobe with metastatic liver. Then the THP levels of normal liver tissue and tumor of median left lobe and lateral right lobe. The THP levels of tumor under portal occlusion tended to be about 2.63-fold higher than without occlusion. These results suggest that hepatic arterial injection under portal occlusion is more useful to increase the levels of anticancer agents of metastatic liver tumor.

Animals↗
PubMed1992

[Hyperthermia for cancer with dextran magnetite using tubular implants].

Dextran magnetite particles (Meito Sangyo Corp.) are an aqueous magnetite zol and a nanometer complex consisting of dextran chains surrounding a core of ultrafine iron oxide. The tubular implants were made with polyester tube (3 mm diameter, 20 mm length) filled with DM aqueous zol (29%w/v). The temperature of an agar phantom with implants was measured in the inductive field. Heating was effected by creating an electromagnetic field with a 7 kW generator operating at 500kHz (Yamamoto Vinyter). The temperature was elevated 3.4 degrees at a distance of 5 mm from the implant at an inductive power of 2.6 kW. An area of 20 x 20 mm was heated while changing the power, the number of implants, and their arrangement. Selective heating of cancer was considered possible by inductive heating at 500 kHz and DM implants. Since the DM aqueous zol configuration can be readily changed, treatment of various cancers is possible.

Dextrans↗
PubMed1992

[Activities of antithrombin III and heparin cofactor II in patients with pathologic blood coagulation conditions].

To investigate the physio-pathological functions of HC-II, assays for HC-II and AT-III were performed simultaneously on the samples from patients with DIC, liver dysfunction or renal disease from the three view points of consumption, production and loss of AT-III and HC-II. For the AT-III activity, two kinds of assays were applied: the automatic chromogenic substrate method and a newly developed clotting method which receives no effects from HC-II activity. The activity of HC-II was significantly lower than that of AT-III in patients with either DIC or liver dysfunction. However, no significant difference between HC-II and AT-III activities in patients with either thrombosis or renal disease. There were high correlations between HC-II and AT-III activities were found in the patients with liver dysfunction, suggesting that low activity was due to decreased production of HC-II and AT-III in the liver. It will be necessary that elucidation of the significant functions of HC-II not only in coagulation and hemostasis but also in regulation of local inflammation and invasion of neoplasm is necessary.

Adult↗
PubMed1991

Augmentation of murine lymphokine-activated killer cell cytotoxicity by beta-cyclodextrin-benzaldehyde.

We investigated the effect of beta-cyclodextrin-benzaldehyde (CDBA) on lymphokine-activated killer (LAK) cell activity of spleen cells from normal or RCT(+)H-2(+)-sarcoma-bearing C3H/He mice. CDBA augmented the induction of LAK cytotoxicity in vitro against RCT(+)H-2+ tumor cells by IL-2, whereas the culture with CDBA alone did not. In a LAK cytotoxicity assay in vitro, the augmentative effect of CDBA was strongly exerted against spleen cells originating from 2-week-tumor-bearing mice, rather than those from normal mice or mice that had born tumors for 5 weeks. Such an augmentative effect was not observed against other tumor cells (YAC-1, D-6, Colon-26 and EL-4 cells) non-specifically. When the intravenous adoptive transfer of LAK cells was carried out in the mice, LAK cells from tumor-bearing mice induced by combined culture with interleukin-2 (IL-2) and CDBA markedly inhibited the pulmonary metastases of RCT(+)H-2+ tumor, while neither LAK cells from the same tumor-bearing mice induced by only IL-2 nor those from normal mice inhibited the pulmonary metastasis. The majority of LAK cells induced either by IL-2 plus CDBA or by IL-2 alone were found to be Thy1.2+ and asialoGM1+ cells by flow-cytometric analysis, but no obvious phenotypical difference was observed between them. However, the most significant effect of CDBA might be the maintenance of the Lyt-2+ cell level in the spleen cells from tumor-bearing mice. These results suggested that the costimulation of spleen cells with IL-2 and CDBA might induce cytotoxic T cells specific for syngeneic tumor cells.

Animals↗