Search PubMed⌕ Search

Biomedical subjects

N Horikoshi

Publications and source records attributed to N Horikoshi.

At least 127 records · Page 7Linked to original sources

[Colony formation of solid tumors in in vitro colony assay (human tumor stem cell assay)].

Colony forming ability of solid tumor cells was studied in a tumor colony assay (human tumor stem cell assay). In 50 cases of solid tumors, cloning efficiencies of 5 X 10(5) cells plated were as follows: breast cancer 12/12 (100%), colon cancer 10/11 (91%), ovarian cancer 9/9 (100%), sarcomas 7/9 (78%), gastric cancer 3/6 (50%), endometrial cancer 2/2 and pancreatic cancer 1/1. An overall cloning efficiency was 88% (44/50) and this rate is higher than those reported in literatures. Ovarian cancer showed the highest plating efficiency of 0.07% (number of colonies/number of cells plated X 100%) in various solid tumors tested. Subsequently, plating efficiencies of colon and breast cancer were 0.03 and 0.01%, respectively. In the cases of sarcomas and gastric cancer, low plating efficiencies were seen (0.008%, 0.003%). The overall rate succeeded colony growth of solid tumors was somewhat higher in enzymatically treated tumor cells, that is, cloning efficiencies in mechanical and enzymatic methods were 85 and 90%, respectively. The enzymatic disaggregation is an advantageous method in gastric cancer and sarcomas. Various solid tumors can be formed colonies in soft agar and chemosensitivity test using in vitro colony assay is expected in solid tumors.

Breast Neoplasms↗

[Combination chemotherapy of Hodgkin's disease with vincristine, cyclophosphamide, procarbazine, and prednisolone].

Nineteen patients with stages II B-IV of Hodgkin's disease were treated with a combination of vincristine, cyclophosphamide, procarbazine, and prednisolone (CVPP regimen), given in a 3 week intervals for 3 months. Eighteen patients were available for responses. A complete remission (CR) was obtained in 9 (50%) out of 18 patients. The median duration of CR and relapse-free survival were 7 months and 26+ months, respectively. Hematologic toxicity was mild, although occasionally cumulative for aged patients and for previously treated patients. Other toxicities such as alopecia and neurotoxicity were troublesome but reversible. Thus, a further study by modification of the regimen warranted to improve the response rate and relapse-free survival.

Adult↗

[Phase I-II studies of a new antineoplastic agent, 4'-(9-acridinylamino)-methanesulfon-m-anisidide (AMSA)].

AMSA, an acridine derivative with significant antitumor activity in experimental tumors, was administered to 17 patients with advanced tumors refractory to standard chemotherapies. A phase I study was undertaken in 10 patients with solid tumors and lymphomas. Dose-limiting toxicity was myelosuppression. With a median dose of 90 mg/m2 (75-148 mg/m2), median lowest WBC count was 1,000/mm3 (100-3,200) on day 11 and its recovery up to 4,000/mm3 was seen on day 21, while lowest platelet count was 42 X 10(3)/mm3 (7-300 X 10(3) on day 12 and its recovery up to 100 X 10(3)/mm3 was on day 20. Non-hematological toxicities were nausea (39%), vomiting (11%) and phlebitis (17%) in 18 courses of therapy. The result indicated that the recommended dose schedule for a phase II evaluation was 90 mg/m2, every three weeks. Therapeutic activity was observed in patients with non-Hodgkin's lymphoma (one partial response and two minor responses out of four). Two out of five breast, one ovarian, and one melanoma patients showed stable diseases. Five leukemic patients (three AMLs, one MoL, and one blastic CML) were treated with AMSA, and in these cases cytoreduction of peripheral and bone marrow blasts was seen, but it was not adequate to induce remission. Further clinical trials with this agent are warranted, especially in patients with acute leukemia, lymphoma and breast cancer.

Adult↗

[A combination chemotherapy of ACNU and DTIC for advanced malignant melanoma].

Fourteen patients with advanced malignant melanoma were treated with a combination chemotherapy consisting of ACNU 100 mg/m2 i.v. on Day 1 in 6 week intervals and DTIC 200 mg/m2 i.v. on Days 1 to 5 at 3 week intervals. Four patients had prior chemotherapy and 2 had prior immunotherapy. Excluding 4 patients received the regimen for adjuvant chemotherapy, 10 of 14 patients were evaluable for response. There were 3 patients of partial responses, 3 minor responses, 1 no change, and 3 progressive diseases. The durations of partial responses were 1, 1, and 8 months, respectively, while the survival times in these patients were 5, 21, and 10 months, respectively. Leukopenia less than 4,000/cmm occurred in 10 of 14 patients (71%) and thrombocytopenia less than 100 X 10(3)/cmm in 9 of 14 patients (64%), moreover, these hematologic toxicities were cumulative. Serum GOT and GPT elevated to 3,460 mu/ml and 1,365 mu/ml, respectively in one patient, but this returned to a normal level one month later. Nausea and vomiting were mild to severe in 12 of 14 patients, being most marked on Day 1 and decreasing intensity during the next several days. Other non-hematologic toxicities including skin rash, fever, and phlebitis were noted in each one patient, respectively. Hematologic toxicity of this regimen was a dose limiting toxicity; therefore, intensive supportive therapy to prevent infection and hemorrhage is essential for the management of the patients during this chemotherapy.

Adult↗

[Chemotherapy of malignant lymphoma].

Forty years ago, nitrogen mustard was first used in the treatment of a group of six patients with neoplastic diseases, including lymphosarcoma and Hodgkin's disease at Yale University. Since then different kinds of chemotherapeutic agents have been discovered, which clinical efficacy was reviewed as a single agent and in combination. Especially over the past two decades, the management of malignant lymphoma has improved significantly with combination chemotherapy. Now there are several potentially curative regimens, such as MOPP therapy for Hodgkin's disease, and MOPP (or C-MOPP), CHOP (or HOP), BACOP and COMLA for diffuse histiocytic lymphoma. There are recent trends to include methotrexate in combination and to use two non-cross-resistant regimens alternatively (CVP/ABP, MOPP/ABVD) for improving complete remission rate and remission duration. Treatment for favorable histologies, and clinical features and treatment of adult T-cell leukemia lymphoma were also briefly reviewed.

Antineoplastic Agents↗

[Clinical effects of human fibroblast interferon on malignant tumors].

Human fibroblast interferon(HFIF) was used in 26 patients with various malignant diseases, most of whom had previous chemotherapy. The dosages used were 3 X 10(6) IU or 6 X 10(6) IU of HFIF i. v. daily. Out of 24 evaluable patients, there were 2 partial remissions (CLL 1 and multiple myeloma 1), and 7 stable diseases (multiple myeloma 2, stomach cancer 2, non-Hodgkin's lymphoma 1, CLL 1 and malignant melanoma 1). The majority of the patients experienced fever exceeding 38 degrees C and chills, which became uncommon within several days of treatment. Other side effects included myelosuppression, general malaise, anorexia, hepatic dysfunction and renal dysfunction, which were mild and tolerable.

Adolescent↗

Clinical study of aclacinomycin A.

A phase I study of a new anthracycline antibiotic, aclacinomycin A, was performed in a total of 15 patients with advanced malignancy to determine the maximum-tolerated dose. The gastrointestinal toxicity which occurred was not dose-related and was not severe. Epilation and stomatitis were extremely minimal. Both hepatic dysfunction and hematologic toxicity were dose-limiting. A recommended dose for phase II study was determined to be 2.5--3.0 mg/kg (approximately 100--120 mg/m2) given in 3-week intervals. Objective response was observed in two patients with malignant lymphomas.

Aclarubicin↗

Combination chemotherapy with a new anthracycline glycoside, aclacinomycin-A, and active drugs for malignant lymphomas in P388 mouse leukemia system.

Aclacinomycin-A is a new anthracycline glycoside and has less cardiotoxicity than adriamycin. In an attempt to provide an experimental model of a phase III study of aclacinomycin-A, particularly for the treatment of malignant lymphomas, various therapeutic designs of combinations of this drug with other conventional agents were investigated using a P388 mouse leukemia system. Aclacinomycin-A showed no treatment schedule dependency in this tumor system and the optimal dosage of this drug was twice higher than that of adriamycin on each treatment schedule; i.e., single treatment on day 1, three treatments on days 1, 5, and 9, or 10 treatments on every other day from days 1 to 19 after an inoculation of 10(6) leukemic cells on day 0. This antibiotic was ineffective against an adriamycin-resistant subline of P388 leukemia. Among combinations of aclacinomycin-A with cyclophosphamide, vincristine, procarbazine, or bleomycin, the combinations of aclacinomycin-A with cyclophosphamide or vincristine showed a therapeutic synergism in P388 leukemia system.

Animals↗

Combination chemotherapy of 6-thioguanine with various antitumor agents against murine leukemia L-1210.

Antitumor activity of 6-thioguanine against L-1210 leukemia was studied in combination with various antitumor agents in clinical stages, such as mitomycin-C, carbazilquinone, cyclophosphamide, 3,3'-dimesyloxydipropylamine tosylate (864T), 4-hydroperoxyisophosphamide, and 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chlorethyl)-1-nitrosourea hydrochloride (ACNU). The combination treatments with 6-thioguanine and each of six agents, especially with ACNU, showed a distinct therapeutic effect against the early L-1210 leukemia at dosage levels not producing any significant antitumor activity with each agent alone (ip-ip). The excellent antitumor activity of the combination of 6-thioguanine with ACNU was also proved in various sites of tumor inoculation and routes of drug administration systems, i.e., ip-iv, iv-ip, and iv-iv systems. Moreover, the effectiveness of the combination of these two drugs was clearly shown against advanced L-1210 leukemia which was refractory to each agent alone.

Animals↗

Ticarcillin therapy of infections.

Ticarcillin was administered as initial therapy during 73 episodes of infections occurring in 69 adults with neoplastic diseases. During the first six infections, doses of 5 gm were dissolved in 200 ml of solvent and administered intravenously over a 2-h period every 6 h. Four of six infections responded to therapy. However, two of the five Pseudomonas infections failed to respond, whereas the organisms causing the infection were sensitive to ticarcillin in vitro. During the remaining 67 infections, doses of 3.5 g were similarly dissolved and administered intravenously over a 2-h period every 4 h. The overall response to ticarcillin in these 67 infections was 43%. However, 18 of 20 Pseudomonas infections, three Proteus spp. infections, and one infection caused by H. influenzae responded. Only 1 of 7 infections caused by mixed organisms and 5 of 13 infections in which the etiologic agent could not be identified responded. Ticarcillin was ineffective against the majority of Escherichia coli and Klebsiella spp. infections, organisms which were resistant to ticarcillin in vitro. The majority of patients were neutropenic, but the response rate was not dependent on the number of circulating polymorphonuclear neutrophilic leukocytes. Superinfection occurred in seven patients. Erythematous skin rash occurred in two patients, which subsided after discontinuation of the drug. No liver or renal toxicity occurred that could be attributed to ticarcillin.

Adult↗