Biomedical subjects

J Kojima

Publications and source records attributed to J Kojima.

112 records · Page 7Linked to original sources

PubMedDate not supplied

Reduction of nonselective adsorption of proteins by hydrophilization of microfiltration membranes by radiation-induced grafting.

Alcoholic hydroxyl groups were introduced into a polyethylene microfiltration (MF) membrane by radiation-induced graft polymerization of 2-hydroxyethyl methacrylate (HEMA), vinyl acetate (VAc), and glycidyl methacrylate (GMA). Subsequently, the VAc- and GMA-grafted membranes were quantitatively hydrolyzed into monool (single hydroxyl) and diol groups, respectively. The pure water flux of the modified membrane and the saturation capacity of bovine gamma-globulin onto the membrane were determined as a function of alcoholic hydroxyl group density. The threshold value for hydrophilization ranged between 5 and 7 mol of alcoholic hydroxyl group per kilogram of original MF membrane. Masking of the polyethylene surface with grafted polymer branches containing the diol groups was effective because approximately 70% of the pure water flux of the original MF membrane was maintained. Irrespective of the pore diameter of the original MF membrane, saturation capacities on the modified membrane correlated well with the diol group density. Saturation capacities of bovine gamma-globulin and bovine serum albumin were reduced to 1 mg/m2 of the membrane. In addition, the binding interaction changed from irreversible to reversible.

Adsorption↗

PubMedDate not supplied

Metabolic properties of the acid and lactone forms of HMG-CoA reductase inhibitors.

To gain a better understanding of the metabolic properties between the open acid and lactone form of HMG-CoA reductase inhibitors (statins), the paper focused primarily on characterizing the metabolic properties of statins. We compared the metabolism of the acid and lactone forms of several statins, including atrovastatin, simvastatin, cerivastatin fluvastatin, pitavastatin and rosuvastatin with respect to metabolic clearance, CYP enzymes involved and drug-drug interactions. A remarkable increase in metabolic clearance was noted for all lactones compared with all acids except for pitavastatin lactone. The metabolic clearances of the atrovastatin, simvastatin, cerivastatin, fluvastatin and rosuvastatin lactones were 73-, 70-, 30-, 7- and 64-fold higher, respectively, than those of the corresponding acids. CYP2Cs were critically involved in the metabolism of cerivastatin, fluvastatin and pitavastatin acids. In contrast, CYP2Cs were not involved in the metabolism of the corresponding lactones and CYP3A4 was mainly involved. Moreover, a substantial difference in the metabolic inhibition of statins was found between acids and lactones. Overall, the study demonstrates that CYP-mediated metabolism of lactones is also a common metabolic pathway for statins and that the CYP3A4-mediated metabolism of the lactone forms clearly will need to be taken into account in assessing mechanistic aspects of drug-drug interaction involving statins.

Cells, Cultured↗

PubMedDate not supplied

A phase II trial of mitomycin C, 5'-deoxy-5-fluorouridine, etoposide and medroxyprogesterone acetate (McVD-MPA) as a salvage chemotherapy to anthracycline-resistant tumor in relapsed breast cancer and its mechanism(s) of antitumor action.

To assess the therapeutic efficacy in the combination of mitomycin C (MMC), 5'-deoxy-5-fluorouridine (5'-DFUR), etoposide (VP-16) and medroxyprogesterone acetate (MPA) (McVD-MPA) to anthracycline-resistant tumor as a salvage chemotherapy, a phase II trial was conducted in patients with relapsed breast cancer. Fifty-five patients were enrolled in this trial and 54 were assessable, who had all previously been treated with an anthracycline regimen. The treatment schedule was designed with the intravenous administration of MMC (6 mg/m2) on day 1 followed by peroral administration of VP-16 (75 mg/m2) on day 2, 4, 6 and the peroral administration of 5'-DFUR (600 mg/m2) and MPA (400 mg/m2) on day 1 through 21 in one cycle. The overall tumor response rate was 40.7% (22/54) including 16.6% (9 cases) in complete response and 24.0% (13 cases) in partial response, and the long no change (NC) was observed in 18.5% (10/54) out of 44.4% (24/54) in NC. Of the patients with primary resistance to anthracycline 30.0% responded to McVD-MPA therapy. Bone and liver metastases responded in 50.0% and 50.0%, whereas soft tissue and lung metastases responded in 36.8% and 35.2%, respectively. The mean time to response and response duration were 2.7 and 15.6 months, respectively. The overall survival of the patient treated with the McVD-MPA was superior to the non-treatment of second line therapy, and the median survival between McVD-MPA and non-treatment was 86 days and 50 days, respectively. The major adverse effect was observed in hematological toxicity (31.7%) such as leukopenia and thrombocytopenia and non-hematological toxicity of gastrointestinal events (31.7%), the toxicity was less than grade 2, and was tolerable during the treatment. In the experiment of MDA-MB-231 breast cancer cell line that was overexpressed with P-glycoprotein (P-gp) and multidrug resistance associated protein (MRP), the mechanism(s) by which McVD-MPA induces the antitumor effect to anthracycline-resistant tumor may be explained at least in part as follows: i) The treatment of MMC suppressed the expression of P-gp and MRP in a dose-and time-dependent manner, connecting the increase of the intracellular concentration of VP-16; ii) The treatment of MMC enhanced the expression of thymidine phosphorylase to increase the production of 5-FU from 5'-DFUR in the antiangiogenic effect of MPA. These results indicate that the combination chemotherapy of the McVD-MPA may be an effective regimen to anthracycline-resistant tumor as a salvage chemotherapy to prolong the survival in the patient with relapsed breast cancer.

ATP Binding Cassette Transporter, Subfamily B↗

PubMedDate not supplied

A case of complete response to esophageal cancer by a novel concurrent chemoradiation therapy.

BACKGROUND/AIMS: A combination of chemotherapy and radiotherapy (chemoradiation therapy) has recently been developed for the treatment of non-operable esophageal cancer patients. Chemoradiation therapy is based on the concept of biochemical modulation effects and radiosensitizing effects of chemotherapeutic agents. However, the optimal choice of chemotherapeutic agents and their doses, as well as chemotherapy and radiotherapy regimens have not been precisely established. METHODOLOGY: Based on our recent experience of an effective chemoradiation therapy protocol which consisted of 5-fluorouracil (5-FU) combined with daily concurrent cisplatin and radiation, in addition to the recent knowledge on the biochemical modulation between 5-FU and cisplatin or between leucovorin and 5-FU, we have developed a complete daily concurrent chemoradiation therapy for non-operated esophageal cancer as a treatment modality with curative intent. RESULTS: We report here a novel intensive concurrent chemoradiation protocol by which complete response could be achieved. A low dose of 5-FU (250 mg/body/day) was continuously infused over 24 hours followed by leucovorin (30 mg/body), and a low dose of daily cisplatin (5 mg/body) was administered 1 hour before radiotherapy (2 Gy/day). The administration schedule was 5 consecutive days, followed by a 2-day withdrawal, and then repeated weekly for 4 weeks. CONCLUSIONS: Our completely daily concurrent chemoradiation therapy is rational, effective, and safe, because an endoscopically and pathologically complete response without severe side effects was able to be achieved and this has continued for at least 6 months after chemoradiation therapy. Therefore, we believe that our completely daily concurrent chemoradiation therapy can be recommended for non-operated esophageal cancer patients.

Adenocarcinoma↗