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Biomedical subjects

T Takaoka

Publications and source records attributed to T Takaoka.

At least 73 records · Page 4Linked to original sources

Neoadjuvant chemotherapy in maxillary sinus carcinoma with cisplatinum and peplomycin intraarterial infusion.

The purpose of this paper is to present our preliminary assessment of a new multimodal treatment including neoadjuvant chemotherapy with cisplatinum and peplomycin for maxillary sinus carcinoma. Fifteen patients with squamous cell carcinoma of the maxillary sinus carcinoma seen at Keio University Hospital, with Stage III and IV disease, were enrolled in this trial between January 1982 and January 1985. Regimen of chemotherapy was as follows: day 1, 50 mg/m2 of cisplatinum, intraarterial infusion over 2 hr, days 2-6, peplomycin at a dose of 5 mg/day, intraarterial infusion over 5 hr. Routinely, radiotherapy of 40 Gy by Linac was given to the primary site, concomitantly combined with 5-fluorouracil intraarterial injections only during the first 10 days, 2 weeks after the end of initial chemotherapy. Additional treatment was performed according to the extent of residual tumor. Response to initial chemotherapy revealed that complete response was achieved in 7 and partial response in 6 out of 15 patients with a response rate of 87%. Nine patients required no surgical intervention while 6 underwent a surgical resection. Median follow-up in this group of patients is 20 months. Thirty-month survival rate calculated by Kaplan-Meier's method was 83%. Chemotherapy toxicity was mild in most cases. This pilot study does not provide conclusive survival information, but the results obtained are encouraging.

Aged↗

Clinical trials on UFT in the treatment of head and neck cancer.

A new anticancer agent, UFT which is a mixture of 1-(2-tetrahydrofuryl)-5-fluorouracil and uracil in a molar ratio of 1:4 was administered orally at a dose of 600 mg/day every day. Forty-three patients were evaluable. Eight patients achieved a complete response and eight achieved a partial response with an overall response rate of 37.2%. In terms of response by histology, a response rate was 32.4% (11/34) in cases of squamous cell carcinoma and 75% (3/4) in cases of adenocarcinoma. A response rate by primary site was 57.1% in the nose and paranasal sinuses, 50.0% in the oropharynx and 30.0% in the oral cavity. A response rate was 36.1% in patients with prior treatment and 42.9% in patients with no prior treatment, but there was no statistical significance. Eight of 43 patients developed toxic effects. Most of them were mild such as anorexia, nausea, and stomatitis, but in one case of maxillary sinus carcinoma, severe bone marrow suppression was observed. UFT is a considerably effective and useful drug in the treatment of head and neck cancer. It is possible to increase cure rate by examining various usages of UFT.

Adult↗

Ouabain-resistant cells cultured in a synthetic medium.

Several strains of kidney and liver cells cultured in a synthetic medium were found to be resistant to ouabain. These cell strains were characterized because this resistance may serve as a good marker in genetic studies on somatic cells in chemically defined conditions in the absence of Na+ related growth factors and hormones. The phenotype was stable in the absence of selection for at least two years, and the original strains before adaptation to the synthetic medium were found to have ouabain sensitivity equal to the corresponding cells in the synthetic medium. The resting membrane potential, Na+,K+-ATPase activity, and growth rate of the resistant cells were similar to those of ouabain-sensitive cells. The resistance of the cells was not affected by serum or antibodies against some cytoskeletal proteins and the sensitivity of the Na+,K+-ATPase was not restored by partial purification of the membranes. Western blotting of the Na+,K+-ATPase of the ouabain-resistant cells showed that the molecular weights of its two subunits and its immunoreactivity were similar to those of the enzyme from the ouabain-sensitive strain. Thus the ouabain resistance is caused not by ouabain-like hormone produced by the cells or change in the cytoskeletal system, but by a mutation resulting in expression of an ouabain-resistant ATPase gene.

Animals↗

[Multidisciplinary treatment of head and neck cancer].

A new multidisciplinary treatment for head and neck cancer was shown by focusing on the maxillary and oropharyngeal carcinoma. Neo-adjuvant chemotherapy which consists of cisplatin and peplomycin was incorporated into it. In terms of maxillary carcinoma, 2 courses of chemotherapy were given with an interval of 2 weeks, followed by radiotherapy (40 Gy) combined with intraarterial chemotherapy (5-FU). When no cancer cells were detected at the completion of this therapy, adjuvant chemoimmunotherapy was given. When an apparent tumor was still revealed by CT, radical surgery was performed. When cancer cells were detected only by histological examination, additional radiotherapy up to 60 Gy was given by Linac. The results obtained were analysed in 14 cases. We also presented another type of multidisciplinary treatment in oropharyngeal carcinoma.

Aged↗

[Preoperative chemotherapy for head and neck cancer].

The authors have studied preoperative chemotherapy for head and neck cancer since 1963, focusing on intra-arterial chemotherapy. The results obtained revealed that preoperative chemotherapy played an important role in the improvement of 5-year survival in maxillary sinus carcinoma and tongue carcinoma. However, functional and cosmetic damage after radical surgery has newly energed as problems to be resolved. The appearance of cisplatin has raised an important the level of effectiveness of cancer chemotherapy in recent years. Since the combination of cisplatin and bleomycin analogs revealed a remarkable synergistic effect in experimental chemotherapy, it has been used clinically as preoperative or preradiation chemotherapy for advanced Stage III and IV head and neck cancer. Under the above-mentioned circumstances, treatment for head and neck cancer has undergone various changes over the past twenty years. At present it is no exaggeration to say that the period in which dependence was placed on only surgery and/or radiation is over. The authors would like to emphasize that preoperative chemotherapy should be carried out as a part of multidisciplinary approach under a new concept of neo-adjuvant chemotherapy which includes not only preoperative chemotherapy but also preradiation chemotherapy. The role of preoperative chemotherapy, its current status and future prospects are discussed in this paper, looking back on the history of chemotherapy for head and neck cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Apheresis: clinical response to patients unresponsive to conventional therapy.

Ten of 13 (76.9%) rheumatoid arthritis (RA) patients having intensive cryofiltration treatment showed improvement and 5 of 7 (71.4%) of RA patients treated on maintenance cryofiltration therapy showed improvement. Encouraged by these results, 2 centers were established for controlled trial studies of RA patients. Four of 4 (100%) rheumatoid vasculitis patients treated by cryofiltration and 4 of 7 (57.1%) patients treated with plasma exchange showed clinical improvement. An SLE patient with thrombocytopenia showed a dramatic rise in platelet count during intensive (3 day/wk) plasma exchange treatments despite little prior response to drugs, platelet infusions and splenectomy. Plasmapheresis was effective in improving clinical symptoms and lipid abnormalities in a primary sclerosing cholangitis patient without causing hypoproteinemia during the long-term therapy (4 yrs).

Adult↗

[Humoral and cellular immunodepression following surgery and postoperative infection].

The correlation between humoral and cellular immunodepression and postoperative infection was studied. Our previous study showed that the incidence of postoperative infection was significantly higher in the patients with malignant disease than in those with benign disease. In order to assess the difference, serial determinations of humoral immuno-factors and cellular immuno-functions were performed on 60 patients with benign disease (group A) and 20 patients with malignant disease (group B) before and following surgery. In the group B, the reductions of complement levels, haptoglobulin and transferrin were observed on the 1st and 3rd postoperative days, but in group A, the reductions of these parameters were not so low as those in group B and these parameters recovered progressively. In both groups, patients who had serious reductions of humoral immuno-factors developed postoperative infection. There was no close correlation between the depression of cellular immuno-functions and postoperative infection. Our data suggest that the higher incidence of postoperative infection in group B is responsible for the depression of humoral immuno-factors in the early period of postoperative day.

Antibody Formation↗

[Cancer of the maxillary antrum--a new multidisciplinary treatment containing neo-adjuvant chemotherapy].

During the period 1957-1982, 227 patients with maxillary carcinoma were treated. These cases were divided into 4 groups according to periods and methods of treatment. Five-year determinate survival figures for each group are as follows: I (1957-1966) 22%, 20/91, II (1967-1973) 40%, 27/67, III (1974-1978) 37%, 13/35, IV (1979-1982) 56%, 9/16 (3-year survival). The incorporation of intraarterial chemotherapy into the treatment of maxillary carcinoma has much contributed to an improvement of 5-year survival. Since 1982, a new multidisciplinary treatment containing neo-adjuvant chemotherapy has been introduced into the treatment of this type of carcinoma. Neo-adjuvant chemotherapy: day 1, cisplatin ( CPDD ) 50 mg/m2 or 80 mg/body i.a. over 2 hr., day 2-6, peplomycin (PEP) 5 mg/day i.a. over 5 hr. Two courses of chemotherapy were given with an interval of 2 weeks. Radiotherapy combined with intraarterial chemotherapy: Linac. 40 Gy/4 wks., 5-FU i.a. 250 mg/day q.d. (for 10 days). When no cancer cells were detected at the completion of this therapy, adjuvant chemoimmunotherapy was given. When an apparent tumor was still revealed by CT, radical surgery was performed. When cancer cells were detected only by histological examination, additional radiotherapy up to 60 Gy was given by Linac. The results obtained were analysed in 9 patients who completed this therapy. At the completion of CPDD and PEP treatment, complete response was achieved in 5 cases and partial response in 3 cases with a response rate of 89%. In 2 out of the 9 cases, no cancer cells were detected by histological examination after chemotherapy. No cancer cells were detected in 2 other cases after 40 Gy by Linac. combined with 5-FU i.a. infusion, and in 3 other cases after 60 Gy by Linac. combined with 5-FU. Two patients had radical surgery because of uncontrolled tumors. Periods of follow-up are too short, but it is expected that this new multidisciplinary treatment results in the higher survival.

Aged↗

[High dose methotrexate with CF rescue therapy in patients with head and neck cancer].

A clinical trial of high dose methotrexate (MTX)-CF rescue was conducted in 17 institutions. Forty-seven patients with head and neck cancer entered this trial, of which 29 were evaluable. In this series, the patients were divided into 2 groups (Arm I, Arm II), according to physician's selection. MTX was administered 700 mg/m2 (1000 mg/body) in Arm I and 1750 mg/m2 (2500 mg/body) in Arm II by i.v. drip over 6 hours. Twenty-four hours after initiation of MTX infusion, CF rescue was started. There was no complete response in 29 patients. Four patients showed partial response with an overall response rate of 13.8%. There were 4 partial responders out of 21 patients in Arm I, with a response rate of 19%, whereas there was no partial responders out of 8 patients in Arm II. These results showed no apparent dose response. MTX concentrations in plasma were determined at 6, 24, 48 and 72 hours after initiation of MTX infusion. The assay results revealed a safe range in Arm I, but exceeded in 3 cases of Arm II. GI disturbances were seen at the rate of 78%. Bone marrow suppression was remarkable and hepatic toxicity was observed as the rate of 41%. No renal toxicity was observed. The results of high dose MTX-CF rescue therapy were not better than those of moderate dose therapy, so that we concluded that MTX should be used as one agent at low or moderate dose in combination chemotherapy as far as Japanese patients with head and neck cancer are concerned.

Adult↗

Cryoglobulin removal with cryofiltration in the treatment of cryoglobulinemia.

The technique of cryofiltration has been applied in the treatment of cryoglobulinemia. Good clinical improvement has been demonstrated accompanied by decreases of cryoglobulin levels. Three treatments in a week produced transient improvement of clinical symptoms and reduction of cryoglobulin levels. Follow-up treatments performed at adequate frequency and volume processed maintained relief of symptoms and serologic improvement. The cryofilter demonstrates good selectivity for cryoglobulin removal in cryogel, confirmed by electrophoretic analysis of both the cryogel filtrate from the cryofilter used clinically. Plasma cryofiltration appears to be a safe alternative to plasma exchange, requiring no replacement fluids.

Aged↗

[Studies on a neo-adjuvant chemotherapy for head and neck cancer].

A neo-adjuvant chemotherapy as a preoperative and preradiation chemotherapy was studied in 60 cases of the head and neck cancers. Out of 60, 29 cases were treated with peplomycin (PEP) and 31 with combination chemotherapies which include vincristine (VCR), methotrexate (MTX), bleomycin (BLM), mitomycin C (MMC); VCR, MTX, BLM (Mathé); VCR, MTX, BLM, 5-FU, hydrocortisone (Price-Hill A); hydoxyurea, adriamycin, BLM; VCR, MTX, PEP; cisplatin (CPDD), PEP. In the group treated with PEP, CR was achieved in one case and PR in 14 cases with a response rate of 52%. Five-year survival by Kaplan-Meier's method after all treatment was 34%. In the group treated with combination chemotherapy, CR was achieved in 5 cases and PR in 19 cases with a response rate of 77%. Three-year survival of this group was 82%. Responders to PEP as well as combination chemotherapy were more often rendered disease-free after all treatment than non-responders. We concluded that two courses of VMP therapy (VCR, MTX, PEP) would be appropriate for the outpatients with advanced stage I or stage II, meanwhile two courses of CP therapy (CPDD, PEP) was inpatients with stage III or stage IV as a neo-adjuvant chemotherapy.

Adult↗

Clinical value of the determination of serum guanase activity. Studies on patients and experimental data from mongrel dogs and cultured rat hepatocytes.

Serum guanase activity was measured by a new method and compared with serum glutamic oxalacetic transaminase and glutamic pyruvic transaminase levels in 150 patients with various disorders, 21 dogs with experimental myocardial infarction, and 2 CCl4-treated dogs. Additionally, studies of the effect of CCl4 on enzyme release were undertaken using cultured rat hepatocytes. Glutamic oxalacetic transaminase, glutamic pyruvic transaminase, and guanase activities were found to be significantly elevated in patients with various liver disorders, those with acute myocardial infarction with prominent congestion of the liver, and also in CCl4-treated dogs. However, serum guanase activity was normal in patients with a variety of non-liver-related diseases including acute myocardial infarction, and in dogs with experimental myocardial infarction without liver damage, even when the serum glutamic oxalacetic transaminase and glutamic pyruvic transaminase activities were increased. The glutamic oxalacetic transaminase, glutamic pyruvic transaminase, and guanase activities in the culture medium of rat hepatocytes indicated in the presence of 0.5 mM CCl4 were elevated. These findings indicate that serum guanase activity is a more specific indicator of liver damage than serum glutamic oxalacetic transaminase and glutamic pyruvic transaminase.

Alanine Transaminase↗