Biomedical subjects

M Ohgaki

Publications and source records attributed to M Ohgaki.

35 records · Page 2Linked to original sources

PubMed1995

[Therapy of carcinomatous peritonitis by the angiogenesis inhibitor TNP-470 in mice: analysis of timing and doses for intraperitoneal administration].

In order to perform therapy for carcinomatous peritonitis by a new angiogenesis inhibitor, TNP-470, we investigated the effective timing and the optimal doses for intraperitoneal administration using two mice models. In both carcinomatous peritonitis models caused by M 5076 tumor and B 16 melanoma, the early administration of TNP-470 within one week after tumor inoculation extended the survival times of the mice receiving the drugs, whereas the administration of TNP-470 one week or later after inoculation did not affect the survival time. However, there were significant differences in the effective therapeutic doses of TNP-470 between the two models. It is important to select the best timing and doses for intraperitoneal administration of TNP-470 based on the state of angiogenesis and the sensitivity of the tumor tissues to TNP-470.

Animals↗

PubMed1995

[Endoscopic injection of methotrexate bound to activated carbon particles in the treatment of gastric cancer].

A new dosage formulation (MTX-CH), composed of fine activated carbon particles absorbing methotrexate (MTX), distributes concentrated MTX for long periods of time to the regional lymph nodes as well as to the injection site, in animal experiments. MTX-CH would enhance the therapeutic effects not only on the primary lesion but also on the lymphatic metastasis. As clinical trials, (A) in five patients with early gastric cancer, MTX-CH at 50 to 200 mg/person of MTX was injected endoscopically in and around the primary lesion before operation. Surgically removed specimens showed that three out of the 5 primary lesions had disappeared or were necrotic, and the remaining two lesions had shrunk. (B) Three patients with contraindication to surgery received the endoscopic injection of MTX-CH. The MTX-CH injected at 250 to 1,500 mg/person into and around the primary lesion of relatively early gastric cancer resulted in the complete disappearance of the primary lesions for 14 to 24 months up to the present time without enlargement of the lymph nodes. It was thought that local injection of MTX-CH will be effective therapy, especially for gastric cancer with potential lymphatic metastasis in patients with contraindications to surgery.

Animals↗

PubMed1995

[Trial of a treatment for lymph node metastases in patients with breast cancer using aclarubicin bound to activated carbon particles].

A new dosage formulation (ACR-CH), composed of aclarubicin (ACR) bound to fine activated carbon particles, was developed for the treatment of lymph node metastases in patients with breast cancer. In a mice experimental model, ACR-CH had superior therapeutic effects on lymph node metastases compared to the same dose of ACR aqueous solution. In clinical trials, patients with breast cancer received a local injection of 10 mg/person of ACR in the form of ACR-CH or ACR aqueous solution just before mastectomy. In the regional lymph nodes removed by the operation, the ACR concentration of 40.7 micrograms/g in patients given ACR-CH was higher than the 25.1 micrograms/g in patients given ACR aqueous solution, whereas in blood plasma the concentration was higher in patients given ACR aqueous solution than in those given ACR-CH.

Aclarubicin↗

PubMed1995

[Development of 5-fluorouracil incorporated in microspheres for peritoneal carcinomatosis--animal experiments].

A new dosage formulation (5-FU-MS), composed of 5-fluorouracil (5-FU) incorporated in polyglactin microspheres, was studied by animal experiments, which revealed the following results. Intraperitoneal 5-FU-MS delivered greater concentrations of 5-FU for longer periods selectively to the intraperitoneal tissues, whereas it delivered a lower concentration to the blood plasma, than 5-FU solution did in rats. In mice, the 50% lethal dose value of intraperitoneal 5-FU-MS was 535 mg/kg. The toxicity of 5-FU-MS was less than 1/2 that of intraperitoneal 5-FU solution, of which the 50% lethal dose value was 242 mg/kg. Intraperitoneal 5-FU-MS at 200 mg of 5-FU/kg improved the survival curve of mice with peritoneal carcinomatosis better than the identical dose of 5-FU solution.

Animals↗

PubMed1994

Antigen-induced airway hyperresponsiveness is associated with infiltration of eosinophils in lung tissue, but not with bronchoalveolar lavage eosinophilia or neutrophilia.

To examine the role of airway inflammation in airway hyperresponsiveness (AHR), we developed an animal model of AHR in guinea pigs and examined the histopathologic changes of these airways. Guinea pigs were actively sensitized with dinitrophenylated Ascaris suum extract and challenged with inhalation of the same extract. Six and 24 h after antigen challenge, airway responsiveness to inhaled acetylcholine (ACh), bronchoalveolar lavage fluid (BALF) and lung histology were studied. Airway responsiveness to inhaled ACh increased 6 h after antigen challenge (p < 0.05), but an increase in airway responsiveness was not observed 24 h after antigen challenge as determined by PC300 (the minimum concentration of ACh at which the respiratory resistance exceeded 300% of baseline value). The number of eosinophils and neutrophils in BALF increased 6 and 24 h after antigen challenge compared to sensitized, nonchallenged guinea pigs, peaking at 24 h after antigen challenge. On the other hand, the numbers of infiltrating eosinophils in bronchial and bronchiolar tissues increased 6 and 24 h after antigen challenge compared to sensitized, nonchallenged guinea pigs, peaking at 6 h after antigen challenge. We therefore conclude that AHR after allergen exposure in sensitized guinea pigs is associated with an increase in infiltrating eosinophils in lung tissue but not with BAL eosinophilia or BAL neutrophilia.

Aerosols↗

PubMed1994

[The prevention of peritoneal dissemination of gastric cancer with intraperitoneal activated carbon particles absorbing mitomycin C].

A new drug dosage form comprising activated carbon particles absorbing mitomycin C (MMC-CH) has the advantage of being retained in the peritoneal cavity and distributes a larger amount of mitomycin C for a long time. Some 113 patients with gastric cancer and serosal infiltration were randomly assigned intraperitoneal treatment with MMC-CH and no anti-cancer drugs. There were significant differences in survival rate between the patients who have no visible peritoneal dissemination with MMC-CH and without. Thus, intraoperative intraperitoneal treatment with MMC-CH improves survival after gastrectomy for gastric cancer and seems effective against peritoneal recurrence.

Absorption↗

PubMed1994

Application of hydroxyapatite-sol as drug carrier.

The application of hydroxyapatite-sol as a drug carrier is being developed. Hydroxyapatite-sol which is a suspension consisting of hydroxyapatite nano-crystals, was synthesized using an ultrasonic homogenizer. The size of the crystals was 40 x 15 x 10 mm3 on average and their specific surface area was 100 m2/g. An amount of a glycoside antibiotics adsorbed onto hydroxyapatite nano-crystals was measured. The drug adsorbed 0.2 mg per 1 mg of hydroxyapatite. The affect of the drug adsorbed onto the hydroxyapatite was investigated using cancer cells. The drug, adsorbed onto the hydroxyapatite nano-crystals, inhibited cancer cell growth.

Adsorption↗

PubMed1993

Repirinast inhibits antigen-induced early and late pulmonary responses and airway hyperresponsiveness in guinea pigs.

The antiallergic drug repirinast (30 mg/kg i.p.) significantly inhibited antigen-induced early and late pulmonary responses in guinea pigs. The same dose of repirinast significantly inhibited bronchoalveolar lavage eosinophilia and neutrophilia 5 h after antigen challenge (at the peak of the late response). Histologic examination revealed that repirinast markedly inhibited leukocyte (predominantly eosinophils) infiltration into bronchial tissue. Repirinast also blocked antigen-induced airway hyperresponsiveness to inhaled acetylcholine. The inhibitory effect of repirinast on the infiltration of eosinophils and/or neutrophils into the airway may reflect the inhibition of late pulmonary response and airway hyperresponsiveness.

Airway Resistance↗

PubMed1993

Clinical trials with intraperitoneal cisplatin microspheres for malignant ascites--a pilot study.

A new formulation (CDDP-MS), which is composed of lactic acid oligomer microspheres incorporating cisplatin, has been developed in a dosage form for peritoneal carcinomatosis. In this pilot study, CDDP-MS was used clinically for the treatment of malignant ascites induced by cancers of the digestive organs. Thirteen patients with malignant ascites received an i.p. administration of CDDP-MS, of which 12 received 100 mg and one received 200 mg of cisplatin/person to control the ascites. Total platinum levels in ascites and blood plasma were measured periodically. Intraperitoneal CDDP-MS decreased malignant ascites completely in eight patients and partially in four patients, and thus gave a response rate of 92%. The platinum concentration in ascites was maintained at a high level for a week after administration, whereas the concentrations in blood plasma were low. The side effects were well tolerated. Intraperitoneal CDDP-MS exhibits a marked therapeutic benefit with small systemic side effects for the treatment of malignant ascites.

Adenocarcinoma↗

PubMed1990

A sandwich type enzyme-linked immunosorbent assay for proliferating cell nuclear antigen (PCNA)/cyclin using monoclonal antibodies.

Three hybridomas producing monoclonal antibodies to proliferating cell nuclear antigen (PCNA)/cyclin were newly derived. The specificity of established monoclonal antibodies to PCNA, TOB7, TO17 and TO30, was compared with that of the previously reported PCNA-specific monoclonal antibodies, 19A2 and 19F4. TOB7, TO17 and TO30 reacted with purified PCNA in an enzyme-linked immunosorbent assay (ELISA). A 34 kDa PCNA polypeptide was noted by immunoblotting, the same polypeptide as recognized by 19A2 and 19F4. Epitopes recognized by all those monoclonal antibodies to PCNA were analyzed by competitive inhibition tests using ELISA. The results of those experiments suggested that the epitope recognized by TO17 and TO30 was almost identical to that of 19A2 and closely related to that of 19F4, but different from that of TOB7. Based on those results, a sandwich type ELISA for detection of PCNA was developed using TO17 and TOB7. This system was applied to measure the concentration of PCNA in normal peripheral blood lymphocytes (PBL) before and after stimulation by phytohemagglutinin (PHA), and in tissue extracts from rabbit kidney and thymus (RKE and RTE, respectively). Before mitogenic stimulation, the PCNA concentration in PBL extracts was less than 6 ng/ml (cell concentration 2.5 x 10(7)/ml), but at 48 h after PHA stimulation, when more than 70% of cells were in S phase, its concentration became 1280 ng/ml. RTE which contained many proliferative lymphocytes had much higher concentration of PCNA than RKE. Those results suggested that sandwich type ELISA using TO17 and TOB7 was useful as the quantitative assay to detect blast-transformation and proliferation of cells in vivo.

Antibodies, Monoclonal↗

PubMed1990

Activated peripheral blood mononuclear cells detected by murine monoclonal antibodies to proliferating cell nuclear antigen in active lupus patients.

Hybridoma producing monoclonal antibody to proliferating cell nuclear antigen (PCNA/cyclin) (TOB7, IgG1 kappa) was newly established. Using TOB7, PCNA was detected in the peripheral blood mononuclear cells (PBMC) in patients with systemic lupus erythematosus (SLE). Forty-four of 58 patients with SLE had PBMC expressing PCNA. The percentage of PCNA-positive PBMC in patients with SLE was 0-20% (mean: 2.63%) which was significantly higher (P less than 0.01) compared with normal controls (mean: 0.18%), patients with rheumatoid arthritis (mean: 0.83%), and patients with mixed connective tissue disease (mean: 0.38%). Patients with high numbers of PCNA positive PBMC tended to complicate pulmonary disorders (P less than 0.005), especially pulmonary fibrosis (P less than 0.005). In addition, the percentage of PCNA-positive cells in SLE patients correlated with the disease activity (r = 0.45, P less than 0.01). The lymphocyte subsets of PCNA-positive PBMC were examined, and most of those cells belonged to CD4- or CD8-positive T-cell populations in three lupus patients. Our findings indicate that PCNA-positive activated PBMC are present in SLE patients and the percentage of PCNA-positive PBMC may be used as an indicator of disease activity.

Adolescent↗

PubMed1989

Two distinct monoclonal natural thymocytotoxic autoantibodies from New Zealand black mouse.

Autoimmune-prone NZB and NZB x NZW F1 mice have a large amount of autoantibodies cytotoxic for thymocytes (natural thymocytotoxic autoantibodies, NTA). We established two distinct monoclonal NTAs (NTA260 and NTA204) from a NZB mouse that react with the majority, but not all of these thymocytes. Flow cytometry analysis showed that NTA260 is positive on subpopulations of peripheral T cells from young mice, in which approximately 65% of CD4+ and 85% of CD8+ T cells were NTA260+. NTA260 also reacted with brain tissues of mice and rats, including Purkinje cells in the cerebellum. Western blot analysis showed that the molecular weight of NTA260 antigen was 55 kDa. In contrast to NTA260, NTA204 reacted with peripheral B cells but not with peripheral T cells in mice. NTA204 also reacted with peripheral blood granulocytes and bone marrow myeloid cells from both mice and rats. An immunofluorescence inhibition assay revealed the presence of autoantibodies with specificities of each NTA260 and NTA204 in the sera from NZB mice. As a selective decline in the subset of NTA260+ T cells but not NTA204+ B cells was observed with aging of NZB and NZB x NZW F1 hybrid mice, NTA260 is at least partly related to the observed immunological abnormalities of T cells in these autoimmune-prone New Zealand mice.

Age Factors↗

PubMed1989

Assay method for single-chain urokinase-type plasminogen activator.

A new assay method for measuring single-chain urokinase-type plasminogen activator (scu-PA) activity by quantitative calorimetric assay method is described. The serine enzyme u-PA activates plasminogen to plasmin, and scu-PA is a precursor protein obtained from a tissue culture of human kidney cells. The scu-PA solution was activated by plasmin to two-chain u-PA, which releases p-nitroaniline from pyro-Glu-Gly-Arg-pNA, and the optical density at 405 nm was measured. One unit of scu-PA was defined on the basis of 1 nmol of p-nitroaniline released from the substrate per second. One unit of scu-PA was found to be equivalent to 335 u-PA (two-chain) units (IU).

Calorimetry↗

PubMedDate not supplied

Extensive gastrectomy and carbon-adsorbed mitomycin C for gastric cancer with peritoneal metastases. Case reports of survivors and their implications.

BACKGROUND/AIMS: Extensive gastrectomy, defined as gastrectomy with complete omentectomy and extended lymphadenectomy, improves the survival of gastric cancer patients with peritoneal metastases, even though peritoneal metastasis is considered the end-stage of cancer. MMC-CH, a new dosage formulation of mitomycin C, extended the survival of rabbits with peritoneal carcinomatosis as compared to aqueous mitomycin C. METHODOLOGY: We retrospectively reviewed 114 patients who underwent gastrectomy for gastric cancer with peritoneal metastases. RESULTS: Six patients survived for more than 5 years after the therapy out of 63 patients treated with MMC-CH therapy and extensive gastrectomy for gastric cancer with P1, i.e., metastases to the adjacent peritoneum but no metastasis to the distant peritoneum, or P2, i.e., a few metastases to the distant peritoneum. However, there were no 5-year survivors in patients with P3, i.e., numerous metastases to the distant peritoneum, or in patients treated with incomplete omentectomy, limited lymphadenectomy and no MMC-CH therapy. CONCLUSIONS: The results imply that gastric cancer patients with P1 or P2 have a possible chance to survive more than 5 years when treated with MMC-CH therapy and extensive gastrectomy.

Adenocarcinoma↗

PubMedDate not supplied

Effect of extensive lymph node dissection on the survival of early gastric cancer.

BACKGROUND/AIMS: A retrospective analysis of 628 cases of early gastric cancer was performed to evaluate prognostic significance of extensive lymph node dissection. METHODOLOGY: The patients were assigned to either D0/D1 (n=177) group or D2/D3 group (n=451) according to the extent of lymph node dissection and the survival of the two groups was compared. RESULTS: The survival rate of D2/D3 group was significantly higher than D0/D1 group in the case of both including and excluding unrelated cause of death (p<0.0001 and p<0.005, respectively). CONCLUSIONS: Though early gastric cancer is excellent prognostic disease, very few numbers of patients with recurrence really remain. Our data show extensive lymph node dissection was effective to prolong the survival of patients with early gastric cancer.

Adult↗

PubMedDate not supplied

Local injection of anti-cancer drugs bound to carbon particles for early gastric cancer--a pilot study.

BACKGROUND/AIMS: A new dosage formulation consisting of an anti-cancer drug bound to activated carbon particles was developed for a local injection against early gastric cancer so that the dosage formulation yields chemotherapeutic effects selectively to the lymph node metastases as well as to the primary lesion. METHODOLOGY: As a pilot study, the new dosage formulation, total of 50-200 mg of methotrexate only or total of 200 mg of methotrexate plus 8 mg of mitomycin C, was injected into the primary lesions and the adjacent gastric wall of 8 patients with early gastric cancer, guided by a gastrofiberscope before gastrectomy. The surgically resected specimens were examined histologically for the therapeutic effects on the primary lesion and its nodal metastasis. RESULTS: The therapeutic effects were seen in 2 of 4 lymph node metastases (50%) and 5 of 8 of the primary lesions (63%), as confirmed histologically with degeneration and/or necrosis. CONCLUSIONS: Preoperative local injection of the new dosage formulation will be useful to give chemotherapeutic effects on the potential metastases in the regional nodes as well as to the primary lesion.

Aged↗

PubMedDate not supplied

Complete omentectomy and extensive lymphadenectomy with gastrectomy improves the survival of gastric cancer patients with metastases in the adjacent peritoneum.

BACKGROUND/AIMS: The omentum is the site where peritoneal metastases occur most frequently. It has not been shown whether complete resection of the omenta during gastrectomy improves the survival of gastric cancer patients with macroscopic peritoneal metastases. METHODOLOGY: We retrospectively analyzed 126 patients who underwent gastrectomies for gastric cancer with peritoneal metastases but without hematogenous metastases. The 126 patients were stratified according to their grade of peritoneal metastases into three groups: the P1 patients (patients with peritoneal metastases in the adjacent peritoneum but not in the distant peritoneum); the P2 patients (patients with a few peritoneal metastases in the distant peritoneum); and the P3 patients (patients with many metastases in the distant peritoneum). In each group, the survival and clinicopathological characteristics were compared between patients treated by complete resection of the greater omentum and the lesser omentum plus extensive lymphadenectomy during gastrectomy, versus patients treated by incomplete resection of the omenta and non-extensive lymphadenectomy during gastrectomy. RESULTS: Complete omentectomy and extensive lymphadenectomy during gastrectomy improved survival significantly only in the P1 patients. Other clinicopathological characteristics did not differ between them. CONCLUSION: Complete omentectomy and extensive lymphadenectomy is recommended in patients with peritoneal metastases in the adjacent peritoneum but not in the distant peritoneum.

Adenocarcinoma↗