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H Arioka

Publications and source records attributed to H Arioka.

50 records · Page 3Linked to original sources
PubMed1994

CPT-11: population pharmacokinetic model and estimation of pharmacokinetics using the Bayesian method in patients with lung cancer.

In this study, we aimed to develop a population pharmacokinetic model for CPT-11 and to use the Bayesian method to estimate CPT-11 pharmacokinetic parameters in each of 43 patients who received combined therapy consisting of CPT-11 and etoposide. The group was divided into first and second data sets of 30 and 13 patients, respectively. We developed a population pharmacokinetic model of CPT-11 based on the first data set. The individual pharmacokinetic parameters [area under the concentration curve (AUC) and clearance (CL)] were subsequently estimated by using the Bayesian method on the second data set. Plasma CPT-11 concentrations were measured by high-performance liquid chromatography, and compartmental pharmacokinetic models were fitted by the Bayesian method. The population pharmacokinetic model was developed by using the nonlinear mixed effect model. We selected the volume of the central compartment (Vc), CL, and distribution rate constants (K12, K21) as population pharmacokinetic parameters. The population mean values (CV%) of Vc, CL, K12, and K21 were, respectively, 31.8 (15.7%) liter/m2, 14.1 (27.8%) liter/h/m2, 1.1 (8.4%)/h, and 0.41 (30.3%)/h. Residual intraindividual variability was 22.9%. The optimal sampling regime for estimation of the AUC and CL in using the Bayesian method was the two time points of 1 and 8 h post infusion. The mean predictive error, the mean absolute predictive error, and the root mean squared error were -3.3, 9.4, 3.2% (AUC) and 6.3, 10.0, 3.5% (CL), respectively. We concluded that the AUC and CL of CPT-11 could be estimated from plasma concentrations at two times by using the Bayesian method.

Bayes Theorem↗
PubMed1994

Acute lymphoblastic leukemia and non-Hodgkin's lymphoma with mediastinal mass--a study of 23 children; different disorders or different stages?

Mediastinal tumor was found in both acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). Most cases showed the T-cell phenotype. We query whether these two diseases are in fact different disorders or merely different stages of the same disease. Twelve ALL patients with a mediastinal mass and eleven NHL patients with a mediastinal mass under 15 years of age were studied with respect to cytogenetics, immunophenotype, genotype and clinical features. Clonal chromosome abnormalities were found in 75% (9/12) of the ALL patients and 100% (11/11) of the NHL patients. Of the 20 patients with chromosome abnormalities, 12 (60%) had translocations involving 14q11-13 and 7q35 (8 ALL, 4 NHL). t(9;17)(q34;q23) was found only in 3 patients with NHL. All showed the T-cell phenotype except two, who had none of the chromosomal abnormalities frequently detected in T cell ALL/NHL. In T-cell patients, immunophenotypical staging of ALL showed a predominance of early and common thymocyte phenotypes while that of NHL showed a predominance of common thymocyte phenotypes. All 7 of the T-cell patients examined showed rearrangements of the T-cell receptor beta chain gene. On the other hand, two non-T-cell, non-B-cell patients showed no rearrangement. There were no apparent clinical differences between ALL and NHL patients in age (median 8.6 vs 8.9 years), sex ratio (F/M 9/3 vs 7/4) or in the rate of complete remission (90% vs 100%). Our study demonstrated no relevant clinical, prognostic, or immunophenotypic differences between ALL and NHL with mediastinal mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

[Microtubules and antineoplastic drugs].

Microtubules, which are composed of polymerized tubulin dimers, play an important role in various cell functions. For example, they maintain cell shape, form mitotic spindles in M phase of cell cycle, and carry an axonal transport in nerve cells. Microtubules have also been an important target of cancer chemotherapy. Vinca alkaloids depolymerize microtubules, the mechanisms of which action have extensively been investigated recently. Clinical trials of vinorelbine (navelbine), a new semisynthetic vinca alkaloid, are ongoing in Japan. One of advantages of the drug is reduced risk of neurotoxicity. Estramustine may act on microtubule-associated proteins (MAPs) as well as tubulin. It shows additive or synergistic cytotoxicity preclinically when used in combination with vinblastine. This combination was active against hormone-refractory prostate cancer. Another novel drug rhizoxin, which has a similar mechanism of action to that of vinca alkaloids, is also a promising cytotoxic agent and is examined clinically in Europe. Taxanes, which include paclitaxel (Taxol) and taxotere, are interesting drugs because they promote polymerization of tubulin and stabilize microtubules. They show promising antitumor activity against breast, ovarian and lung cancers. Phase I and II trials are ongoing in Japan. Paclitaxel may also potentiate cytotoxicity of radiation. There are several mechanisms of resistance to microtubule-acting drugs. One is multidrug resistance mediated by P-glycoprotein. Other mechanisms include mutation of tubulin.

Animals↗
PubMed1994

[Three cases of hematologic malignancies with jumping translocation].

We treated three cases of hematologic malignancies (Burkitt's lymphoma, ALL (L3), AML (M0)) with jumping translocations. Tumor formation was easily occurred in all three cases. The location of the jumping translocation was 1q21 in all three cases. Hematologic malignancies with jumping translocation tend to be B-cell lineage and have poor prognosis. The significance of jumping translocation is unknown yet, but it seems that jumping translocation is related to the tumor progression, rather than tumorigenesis. So that the intensive therapy including bone marrow transplantation must be considered.

Adolescent↗
PubMed1993

Jumping translocations of 1q in Burkitt lymphoma and acute nonlymphocytic leukemia.

"Jumping translocations" have been observed mostly in cultured cells. Reports of such translocations in hematologic malignancies are few, and the associated clinical picture is unclear. We report three cases of hematologic malignancies with various unbalanced translocations (so-called jumping translocation) involving trisomy of the long arm of chromosome 1. The first case was a 13-year-old boy with Burkitt lymphoma who showed a very aggressive clinical course. The second case was a 10-month-old girl with acute nonlymphocytic leukemia [ANNL, French-American-British (FAB) classification M0] who had high risk factors, including hyperleukocytosis with a peripheral white blood cell (WBC) count of 300,000/microliters, and who died 7 months after diagnosis. The third case was a 6-year-old boy with Burkitt-like leukemia whose first remission lasted only 1 month. Only 10 cases with jumping translocations, including two cases with Burkitt-like leukemia/lymphoma, have been reported previously. This rare phenomenon may occur with increased frequency in Burkitt-like leukemia/lymphoma and may be an adverse prognostic factor.

Adolescent↗
PubMed1993

Phase I study of CPT-11 and etoposide in patients with refractory solid tumors.

PURPOSE: To determine the maximum-tolerated dose (MTD) and acceptable dose level of a cytotoxic regimen of CPT-11, a new camptothecin derivative, in combination with etoposide (VP-16) and to describe the principal toxicities associated with it. PATIENTS AND METHODS: Patients with refractory solid tumors received VP-16 and CPT-11 daily for 3 consecutive days (days 1 through 3) every 3 or 4 weeks. Groups entered the trial at escalating CPT-11/VP-16 dose levels of 40/60, 60/60, 60/80, and 80/60 mg/m2. Thirty-four patients entered this study, of whom 33 were assessable for toxicity and 22 for therapeutic efficacy. RESULTS: Granulocytopenia was so severe that this regimen required supportive therapy with recombinant human granulocyte colony-stimulating factor (G-CSF). The majority of the patients experienced a 5% weight loss and diarrhea was the dose-limiting toxicity. The MTDs were 60/80 and 80/60 mg/m2 administered on days 1 through 3. Five of seven previously untreated patients with non-small-cell lung cancer (NSCLC) achieved partial responses (PRs) to this therapy, as did two with NSCLC who had received prior chemotherapy, two with head and neck cancer, and one with an adenocarcinoma (primary tumor unknown). CONCLUSION: The recommended dose of CPT-11/VP-16 for this regimen with G-CSF is 60/60 mg/m2 on days 1 through 3 every 3 to 4 weeks. We suggest that the combination of topoisomerase I and II inhibitors is likely to be an effective treatment strategy. The activity of this regimen against NSCLC is particularly encouraging and should be evaluated in a phase II trial.

Adult↗
PubMed1993

[Fulminant hepatitis-like veno-occlusive disease of the liver after allogeneic bone marrow transplantation in acute lymphoblastic leukemia].

A 14-year-old girl with acute lymphoblastic leukemia in second remission received an allogeneic marrow graft from her HLA identical brother. Cyclosporine A and short term methotrexate were given for prophylaxis against graft versus host disease. On day 42 post transplantation elevation of SGOT and SGPT was recognized, rising the next day to 8,560IU and 2,590IU, respectively. Prothrombin activity dropped below 10%. HCV antibody and HBs antigen were both negative. Fulminant hepatitis was diagnosed, therefore plasma exchange was initiated. However, hepatic encephalopathy developed and she died on day 57. The postmortem liver appearance was consistent with early changes of veno-occlusive disease. Such atypical cases of VOD with late onset are difficult to distinguish from fulminant hepatitis but should be kept in mind.

Adolescent↗
PubMed1992

[Successful treatment with combination of methylprednisolone, antilymphocyte globulin and cyclosporine in two cases of aplastic anemia].

Two children with severe and moderate aplastic anemia received combination treatment with methylprednisolone, antilymphocyte globulin and cyclosporine. One child (severe type) was given 2 courses of high dose methylprednisolone during the last 4 weeks without improvement prior to this combination therapy. The other child (moderate type) was not previously treated. Both patients showed complete response within 3 months following this therapy. Serious side effects were not observed. Combination therapy of these three drugs may be beneficial for patients with aplastic anemia.

Anemia, Aplastic↗
PubMed1990

[A case of sarcoidosis demonstrating spontaneous production of interleukin-1 alpha and beta by alveolar macrophage].

A 44-year-old man was admitted for evaluation of dyspnea on exertion and subcutaneous nodules. The chest X-ray on admission revealed bilateral hilar lymph node swelling and diffuse micronodular shadows throughout both lung fields. Ga scintigram demonstrated diffuse abnormal uptake. Serum angiotensin converting enzyme was elevated significantly (86.6 IU/I). The TBLB specimen confirmed the diagnosis of sarcoidosis. The cell numbers in bronchoalveolar lavage fluid was increased (4.4 x 10(8), the percentage of lymphocytes was elevated (64%) and the ratio of Leu 3a+/Leu 2a+ was very high (16.07). We further evaluated the spontaneous IL-1 release in vitro by alveolar macrophages obtained by bronchoalveolar lavage. The results showed that large amounts of IL-1 alpha and beta were produced spontaneously by alveolar macrophages before therapy, followed by a decrease in production after corticosteroid treatment. Previously, the authors reported that no significant amount of IL-1 alpha and beta was detected in 5 normal volunteers and 6 other active sarcoidosis cases which improved without therapy. Therefore, significant amounts of spontaneous release of IL-1 alpha and beta in vitro from alveolar macrophages in sarcoidosis might be considered as an index for the necessity of systemic corticosteroid treatment.

Adult↗
PubMed1988

[Therapy of advanced neuroblastoma by the protocol of the Welfare Ministry used by the Sawaguchi Group].

Five patients with advanced neuroblastoma were treated with the protocol of the Welfare Ministry used by the Sawaguchi group. This protocol consists of cyclophosphamide (CPM), vincristine (VCR), 4'-O-tetrahydropyranyladriamycin (THP-ADM) and cisplatinum (CDDP). Two patients treated with this protocol as the first therapy obtained partial remission. Two patients who had obtained complete remission before the treatment with this protocol remained in complete remission after the treatment. One patient who had shown poor response to the therapy given before treatment with this protocol also showed poor response to the protocol. The most significant side effect with this protocol was myelosuppression, the severity of which was closely related to the dose of THP-ADM. Damage to the liver, kidney and heart was not very significant. We advocate that patients with advanced neuroblastoma can obtain complete remission with the aid of surgery and radiotherapy, etc., if they are treated with the present protocol as the first therapy.

Adrenal Gland Neoplasms↗
PubMedDate not supplied

In vivo effects of apoptosis in asthma examined by a murine model.

BACKGROUND: One of the characteristic features of bronchial asthma is the accumulation of various inflammatory cells, predominantly eosinophils, at the subepithelial region beneath the basement membrane of the airway. Apoptosis is a form of physiological cell death, through which the cellular contents including biologically active substances are kept in the cell membrane and are removed without their harmful effects. So, attempts were made to clarify whether the induction of apoptosis is beneficial in asthma by using a murine model with ovalbumin (OA) as responsible allergen. METHODS: A/J mice, which are genetically predisposed to be hyperresponsive to acetylcholine, were immunized with OA and alum, accompanied by OA inhalation for 2 weeks, during which some of the mice were also treated with either anti-Fas monoclonal antibody or sham control hamster IgG intranasally. Airway responsiveness to acetylcholine was then analyzed by measuring airway resistance with a body plethysmograph box. Apoptosis was assessed by propidium iodide and TUNEL staining. RESULTS: Inhalation of OA increased both airway responsiveness to acetylcholine and the number of cells, mostly eosinophils, infiltrated into the airway. Administration of anti-Fas antibody induced apoptosis in the infiltrated eosinophils and abolished augmentation of airway hyperresponsiveness caused by OA inhalation. CONCLUSION: Induction of apoptosis in proinflammatory cells including eosinophils at the airway may have a beneficial effect on suppressing airway hyperresponsiveness.

Acetylcholine↗
PubMedDate not supplied

Antitumor effects of butyrolactone I, a selective cdc2 kinase inhibitor, on human lung cancer cell lines.

Butyrolactone I, which is a naturally occurring specific inhibitor of the cdc2 kinase family, showed antitumor effects on several non-small- and small-cell-lung cancer cell lines with IC50 values the order of 50 micrograms/ml on the former. No cross-resistance of several drug-resistant cell lines, including those with the multidrug-resistant phenotype and five cisplatin-resistant cell lines to butyrolactone I was observed. The cdc2 kinase activity of PC-14 cells was inhibited by treatment with 20 micrograms/ml butyrolactone I, a concentration comparable to the IC50 value, for 2 hours. Longer exposure to butyrolactone I (> 24 hours) reduced the cdc2 kinase protein level. Butyrolactone I arrested the cells at the G2/M phase in a concentration dependent manner. These results suggest that butyrolactone I actually acts on cdc2 kinase, rather than other cdk kinases, in PC-14 cells. Inhibition of DNA synthesis, determined by measuring thymidine uptake, occurred earlier (2 hours) after initiating exposure than the decrease in the cdc2 protein level and was concentration dependent, suggesting that butyrolactone I inhibited DN4 synthesis. Cell permeabilization by digitonin enhanced DN4 synthesis inhibition by butyrolactone I, suggesting that the permeability of the membrane to this agent was the limiting factor for its growth inhibitory effect. Many anticancer agents, such as alkylating agents and cisplatin, cause cells to accumulate at the G2/M phase of the cell cycle. We investigated whether butyrolactone I had any modulatory effect on the antitumor effects of several anticancer drugs in vitro. Butyrolactone I showed no modulatory effects on vindesine, paclitaxel, or etoposide, but exposure of PC-9 and PC-14 cells to butyrolactone I together with or prior to treatment with cisplatin reduced the cytotoxicity of the latter. Thin-layer chromatographic analysis revealed that butyrolactone I bound to cisplatin, which was a possible cause of the reduced cisplatin cytotoxicity in the presence of bytyrolactone I.

4-Butyrolactone↗