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Biomedical subjects

S Hiraki

Publications and source records attributed to S Hiraki.

At least 73 records · Page 4Linked to original sources

[Establishment of adriamycin-resistant human small-cell lung cancer cells in culture: analysis of the mechanism of resistance and cross-resistance].

An adriamycin-resistant cell line was established in culture by continuous exposure of SBC-3 cells, a cell line of human small-cell lung cancer, to increasing concentrations of adriamycin, followed by a cloning procedure. The resistant cells (SBC-3/ADM) were 30 times more resistant to the drug than the parent cells in terms of 70% lethal dose, determined by soft agar clonogenic assay. Uptake studies using [3H] daunomycin, which was completely cross-resistant to adriamycin, showed decreased influx and enhanced efflux of the agent. This resistance to adriamycin may be attributed to an alteration in membrane transport, resulting in reduced intracellular accumulation of the drug. Using the SBC-3/ADM cells, the activity of a variety of drugs was analyzed by soft agar clonogenic assay in order to search for a means of circumventing drug resistance. The SBC-3/ADM cells were markedly resistant to anthracycline antibiotics such as THP-adriamycin and 4'-epi-adriamycin. The cells were also resistant to structurally or pharmacodynamically unrelated compounds such as vincristine, mitomycin C, 40497S, an active compound of ifosfamide, and etoposide. However, the cells were as sensitive to mitoxantrone as the parent cells, and were considerably susceptible to cisplatin. These results suggest that mitoxantrone and cisplatin may exert a sufficient degree of activity for use against small-cell lung cancer resistant to adriamycin.

Carcinoma, Small Cell↗

[Subcutaneous operation and examination under the universal endoscope].

Endoscopes are mainly used to study the internal structures of organs and tissues with inherent space. These include the gastrointestinal tract, abdominal space and joint space. The standard endoscope, however, cannot be used to evaluate tissues without such space. We have invented a new type of operation tube to be used with the arthroscope. This combination enables us to study subcutaneous soft tissues without inherent space. Our new device is a powerful tool to be used for evaluation of subcutaneous soft tissues in any part of the body. Surgical procedures can also be carried out with this device. Areas of future applications of our device will be extremely wide including orthopaedic surgery, plastic surgery and general surgery. The presentation will discuss the procedure for utilizing this new instrument.

Adult↗

Anticancer drug sensitivity by human tumor clonogenic assay.

The anticancer drug sensitivity of human cancers was tested by the human tumor clonogenic assay (HTCA). Of 152 human cancer specimens tested, 63 (41%) formed more than 30 tumor cell colonies in control plates and could be used to evaluate the drug sensitivity of tumor cells. In 42 (93%) of 45 clinical trials in 24 patients, a parallel correlation was observed between the in vitro anticancer drug sensitivity measured by the HTCA and the clinical response of tumors to anticancer drugs. These results suggest that the HTCA is a good technique for the in vitro test of the anticancer drug sensitivity of human cancers.

Agar↗

[Therapeutic effect of ceftizoxime on infection in patients with lung cancer].

Ceftizoxime (CZX) was given in daily doses of 4 approximately 6 g by intravenous drip infusion to 30 patients with infection accompanying lung cancer to investigate the usefulness of the drug for infectious disease: The rate of effectiveness (marked and moderate) was 73.3% (22/30 patients). Of the 30 patients, 2 had drug fever; 1, arthralgia; and 1, eosinophilia. These side effects improved after the drug was withdrawn. CZX is a very useful antibiotic with high effectiveness and safety in immunocompromised patients with infection accompanying advanced lung cancer.

Adenoma↗

Randomized trial comparing chemotherapy alone and chemotherapy plus chest irradiation in limited stage small cell lung cancer: a preliminary report.

In order to assess the effectiveness of chest irradiation in addition to intensive chemotherapy in limited stage small cell lung cancer, 50 patients were randomized to receive either chemotherapy alone or chemotherapy plus chest irradiation, between April 1981 and October 1985. The chemotherapy regimen consisted of a four-drug combination of cyclophosphamide, vincristine, methotrexate, and procarbazine, and a three-drug combination of etoposide, adriamycin, and nimustine, given alternately every 8 weeks. One group of 26 patients received the chemotherapy alone, and another group of 24 patients received chest irradiation with 40 Gy between cycles 1 and 2 of the chemotherapy. Complete response rates were quite similar in the two groups; 50% for those receiving chemotherapy alone, and 59% for those receiving chemotherapy plus chest irradiation. There were no significant differences in median survival (15 months versus 12 months) and in long-term survival rates between the two groups with a median follow-up period of 26 months. The combined modality treatment was more toxic than chemotherapy alone; two patients receiving such treatment died of radiation pneumonitis. It is concluded that chest irradiation combined with chemotherapy does not affect the response rate, survival, or pattern of recurrence in patients with limited stage small cell lung cancer.

Actuarial Analysis↗

[Sensitivity testing of anticancer drugs using the human tumor clonogenic assay].

The response to cancer chemotherapy varies from patient to patient with the same histologic type of tumor. However, anticancer drugs are considerably toxic to the patient, and it is therefore very important to have an accurate knowledge of the sensitivity of anticancer drugs against an individual patient's tumor in establishing successful chemotherapy. We have investigated the sensitivity testing of anticancer drugs using the human tumor clonogenic assay since 1980. Specimens were obtained by aspiration of ascites, pleural effusions and bone marrow and by biopsy of primary and metastatic tumors. Drugs tested in the present study were adriamycin, aclarubicin, THP-adriamycin, mitoxantrone, 40497s (an active compound derived from ifosfamide), mitomycin C, cisplatinum and methotrexate. One hundred and fifty-two specimens were obtained from cancer patients and tested for their drug sensitivity using the assay. Of the 152 specimens, 63 (41%) formed more than 30 colonies in control plates and could be used to evaluate drug sensitivity. Of these, 45 instances were evaluable for examination in an in vitro-in vivo association, and 42 (93%) showed a correlation between in vitro sensitivity and clinical response. In summary, the results indicated that the human tumor clonogenic assay was an excellent technique for testing the in vitro sensitivity of anticancer drugs. However, technical developments yielding higher colony efficiency would be required to facilitate practical use of the assay.

Antineoplastic Agents↗

[In vitro drug-sensitivity test using human tumor clonogenic assay in lung cancer patients].

It would be helpful for successful chemotherapy in cancer patients if a drug-sensitivity test in vitro could predict the exact response of an individual patient's tumor. We have investigated a drug-sensitivity test using human tumor clonogenic assay since 1980. In this paper, results obtained in lung cancer patients are discussed. Specimens for testing were obtained from primary tumor, metastatic mass, malignant pleural and pericardial effusion, and affected bone marrow. Drugs tested in this study were adriamycin, aclarubicin , THP-adriamycin, mitoxantrone, mitomycin C, cis-platinum, 40497 S (an active compound derived from ifosfamide), and methotrexate. Out of 88 specimens tested, 41 (47%) successfully yielded more than 30 colonies per control dish, and were able to evaluate drug-sensitivity. Of those, 32 instances were valid for examination in an in vitro-in vivo association. As a result, 3 were in vitro sensitive-in vivo sensitive, 2 were in vitro sensitive-in vivo resistant, and 27 were in vitro resistant-in vivo resistant. Accordingly, the true positive rate was 60%, and the true negative rate was 100%. In summary, the human tumor clonogenic assay appeared to be an excellent method for testing drug-sensitivity for an individual patient with lung cancer.

Aclarubicin↗

[Mitoxantrone in the treatment of relapsed and refractory malignant lymphoma].

Mitoxantrone is an anthracenedione with structural similarities to adriamycin but without the amino-sugar moiety on the parent molecule. The compound attracted attention on the basis of animal tumor studies in which it showed equal or superior efficacy compared to adriamycin, but with diminished cardiotoxicity; and it was not fully cross-resistant to adriamycin. Our in vitro studies using human small cell lung cancer cell line (SBC-3) disclosed the absence of cross-resistance between mitoxantrone and adriamycin: SBC-3/ADM, which had developed resistance by continuous exposure to increasing concentration of adriamycin, was as equally sensitive to mitoxantrone as SBC-3 was when tested by clonogenic assay. A phase II study conducted in our Department revealed that mitoxantrone was active to malignant lymphoma refractory to conventional agents including adriamycin: 6 (33%) of 18 patients responded to the agent. Based on the results of our phase II studies of mitoxantrone, etoposide, and cisplatin in malignant lymphoma, we have conducted a phase III study of a 4-drug combination of these 3 drugs plus prednisolone in relapsed or refractory lymphoma: Out of 14 patients, 3 responded completely and 4 did partially, so far. The regimen would appear useful as a salvage therapy for refractory lymphoma.

Adult↗

[Combination chemotherapy with multimodality approaches for small cell carcinoma of the lung].

Small cell carcinoma of the lung (SCCL) is disseminated at the presentation in most patients. Chemotherapy is, therefore, the principal therapeutic modality in this disease. The application of aggressive combination chemotherapy has resulted in an improved survival for patients with SCCL. In an attempt to improve therapeutic results, the current study was undertaken to test a cyclic alternating chemotherapy with the four-drug combination of COMP and a three-drug combination of VP-16, adriamycin and ACNU (VAN), which appeared non-cross-resistant to the former. In this study, also included two randomized clinical trials to test the effectiveness of concomitant chest irradiation in patients with limited disease, and to test the validity of prophylactic cranial irradiation for patients achieved complete remission. In this paper, results of the studies were analysed and discussed.

Antineoplastic Combined Chemotherapy Protocols↗

[Anticancer drug sensitivity tested by tumor stem cell assay].

Accurate in vitro anticancer drug sensitivity is helpful for successful chemotherapy of cancer patients. The purpose of the present study was to evaluate the tumor stem cell assay for the selection of effective drugs for individual patients with cancer and for the in vitro phase II screening of new anticancer drugs. Sixty-six specimens obtained from cancer patients were tested drug sensitivity by this assay. The results showed that this assay as an excellent technique for testing in vitro sensitivity of anticancer drugs against tumor cells from specimens removed from individual patients. The in vitro results correlated with in vivo response data in 93% of the instances observed in vitro-in vivo associations and a true negative rate was 100%.

Antineoplastic Agents↗

Tumor stem cell assay for detecting metastases of human lung cancer.

We applied a tumor stem cell assay using an enriched double-layered soft agar system for the detection of metastatic sites of lung cancer. Lung cancer colonies grew from 7 of 10 effusions cytologically positive for tumor cells and 7 of 10 bone marrow aspirates cytologically and histologically positive for tumor cells. Twenty-six of 29 bone marrow aspirates cytologically and histologically negative for tumor cells showed no colony growth. However, the remaining three bone marrow aspirates, which were obtained from patients with small cell lung cancer, formed colonies in soft agar. These results indicate that the tumor stem cell assay is useful for detecting metastatic sites of lung cancer.

Bone Marrow↗

Combination chemotherapy for small cell carcinoma of the lung: evaluation of four-drug combination of cyclophosphamide, vincristine, methotrexate, and procarbazine.

Forty-one patients with small cell carcinoma of the lung were treated with a four-drug combination of cyclophosphamide, vincristine, methotrexate, and procarbazine. The response rate was 68% (28 responded among 41 patients), with 10 complete responses (24%) and 18 partial responses (44%). The median survival time from the initiation of chemotherapy was 11 months for patients with limited disease and 8 months for those with extensive disease. Patients who achieved complete response survived significantly longer than those who did not; the median survival time for complete responders was 14.5 months, compared to 8.5 months for partial responders and 6 months for non-responders. Myelosuppressive toxicity remained within acceptable limits, with 5% incidence of leukocytopenia (less than 1,000/microliter) and 7% incidence of thrombocytopenia (less than 50,000/microliter) following the first course of the regimen.

Adult↗

Cytological and histological correlation of primary lung cancer: a preliminary study of 106 cases with resectable tumors.

In order to increase the accuracy of diagnosis in lung cancer, analysis concerning cytological and histological correlation was attempted. The present study consists of 106 patients, who were seen during the past approximately five years and underwent radical surgery to remove tumors completely; mere biopsy specimens were excluded. These patients were 63 years old on the average, 78 males and 28 females, 29 cases of the hilar type (H) and 77 of the peripheral type (P), and 27 and 76 cases of the clinical stage I in H and P, respectively. Histologically, there were 53 adenocarcinomas (Ad), 38 squamous cell carcinomas (Sq), 4 adenosquamous cell carcinomas (Ad + Sq), 5 large cell carcinomas (LCC), and 6 small cell carcinomas (SCC); among them, 3 Ad and 21 Sq in H, and 50 Ad and 17 Sq in P. The overall positive percentages were 65.5 (H) and 26.0 (P) by combination of spontaneous, airsol-induced and Saccomanno's methods, against 96.6 (H) and 72.8 (P) with inclusion of brushing method. 94.8% of Sq in H and 66.7% of Ad and 70.6% of Sq in P were positive by the brushing. A comparative study of these four methods, performed at least once on the same patient, also confirmed the superiority of brushing. Cyto- and histological agreement was 21/21 (100%) for Sq in H, whereas 30/34 (88.2%) for Ad and 13/15 (86.7%) for Sq in P. In conclusion, cyto- and histological findings in H and P corresponded well, and as far as cytology of peripheral type is concerned, a combined method, especially with brushing, is strongly recommended.

Adult↗

Pretreatment serum albumin concentration and lactic dehydrogenase activity as prognostic factors in patients with small cell lung cancer.

Pretreatment laboratory parameters were analyzed as prognostic factors in patients with small cell lung cancer. Serum lactic dehydrogenase activity, serum albumin concentration, PPD skin reaction, and peripheral lymphocyte count were of prognostic importance. When these factors were evaluated by multivariate analysis together with performance status and disease extent, lactic dehydrogenase and albumin were the most influential factors related to survival.

Carcinoma, Small Cell↗

Bone marrow examination for detection of metastasis in patients with bronchogenic carcinoma: an evaluation of 107 patients.

As a staging procedure before treatment, examination of bone marrow from the posterior iliac crest was performed on a total of 107 patients with bronchogenic carcinoma. Among them, 11 patients (10.3%) had metastasis in the bone marrow: five of 39 adenocarcinomas, five of 33 small cell carcinomas, one of four large cell carcinomas, and none of 31 epidermoid carcinomas. Leukoerythroblastosis was found exclusively in the patients with metastasis, although the presence of tumor cells in the bone marrow did not correlate well with peripheral blood cell counts. Survival following an intensive chemotherapy in patients with bone marrow metastasis was substantially longer for those with small cell carcinoma than for those with other histologic types of bronchogenic carcinoma.

Biopsy↗