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Biomedical subjects

K Kikuchi

Publications and source records attributed to K Kikuchi.

At least 1,099 records · Page 61Linked to original sources
PubMed1986

CAP therapy for advanced, recurrent and/or metastatic malignant tumors of the head and neck.

One-day CAP therapy utilizing CPM, THP-ADM and CDDP was performed on 33 patients with malignant tumors in the head and neck region which were able to be evaluated. As a result, CR was obtained in 6 patients and PR in 11 patients; thus the overall response rate was 51.5%. The present therapy is worthwhile as a neo-adjuvant chemotherapy and it was effective in patients with relatively severe systemic condition or those with lung metastasis. When the tissues were classified histologically, the present therapy was effective against anaplastic carcinoma and adenocarcinoma. Since agents significantly effective against adenocarcinoma have not been available so far, the present therapy is considered to be a useful method especially for the treatment of adenocarcinoma. Moreover, because irreversible side effects scarcely appeared and because the period for 1 course of treatment is short enough, the present therapy is considered to be a method with little burden on patients.

Adenocarcinoma↗
PubMed1986

Combination chemotherapy with CDDP and 5-FU in head and neck cancer.

Combination chemotherapy with CDDP and 5-FU was performed in 19 patients with evaluable head and neck cancer and 2 CR patients and 7 PR patients were obtained; thus the response rate was 47.4%. Histologically, the present therapy is considered to be especially effective against well differentiated squamous cell carcinoma (83.3%). The present therapy is considered to be useful as a neo-adjuvant chemotherapy (75.0%), but it is desirable to perform at least 2 courses of treatment. The side effects observed were nausea, vomiting, anemia, leukocytopenia and alopecia, etc., and most of them were reversible. However, there were 2 patients in which the continuation of chemotherapy was impossible due to renal disorders.

Adenocarcinoma↗
PubMed1986

Combination chemotherapy with CDDP, 5-FU and PEP in head and neck malignant tumors.

Multi-drug combination therapy with CDDP, 5-FU and PEP was performed in 23 patients with malignant tumors in the head and neck region, and 2 CR patients and 9 PR patients were obtained with a response rate of 47.8%. The present therapy (CFP therapy) is considered to be especially effective against patients at low performance status grades with poorly differentiated squamous cell carcinoma which is located in regions receiving an abundant blood supply like the oral cavity. It is advisable to perform more than 2 courses of treatment as an induction chemotherapy. With respect to the method of administration of PEP, further study will be made in the future.

Adult↗
PubMed1986

T-lymphocyte subsets in patients with squamous cell carcinoma of the head and neck.

T-lymphocyte subsets in the peripheral blood of patients previously untreated for squamous cell carcinoma of the head and neck were investigated using monoclonal antibodies under flow cytometry before starting treatment. T-lymphocyte subsets in the peripheral blood of patients with squamous cell carcinoma did not significantly differ from those in the peripheral blood of healthy subjects, patients with benign tumors of the head and neck, patients with chronic sinusitis and patients with benign otolaryngological diseases. The necessity to investigate the function of T-lymphocyte subsets was suggested. It was furthermore suggested that T-lymphocyte subsets in cancerous tissues should be investigated.

Adult↗
PubMed1986

Effects of epidermal growth factor on the syntheses of DNA and polyamine in isoproterenol-stimulated murine parotid gland.

The effects of epidermal growth factor (EGF) on isoproterenol (IPR)-stimulated DNA synthesis and the activities of the rate limiting enzymes of polyamine synthesis (ornithine and S-adenosylmethionine decarboxylases) in parotid glands were investigated in vitro in cultured rat parotid explants and in vivo in submandibulectomized mice (mice after bilateral removal of the submandibular and sublingual glands). When the explants were cultured on siliconized lens paper floating on chemically defined synthetic medium, IPR caused the increases of both tissue cAMP level and the two decarboxylase activities in the prereplicative period and the stimulation of DNA synthesis with similar time courses to those observed in vivo. Dibutyryl cyclic AMP (DBcAMP) also increased the enzyme activities, but not DNA synthesis. EGF (1-2 ng/ml) had little effect on the IPR- and DBcAMP-dependent increases of amylase secretion and the enzyme activities, but it markedly enhanced IPR-stimulated DNA synthesis. Moreover, increase in DNA synthesis by DBcAMP was clearly observed in the presence of EGF when the explants were treated with this nucleotide analogue only during the early prereplicative period. In in vivo experiments, IPR-dependent increase in DNA synthesis was less in submandibulectomized mice than in intact animals. This decreased response to IPR of DNA synthesis was completely reversed by administration of EGF, though EGF alone did not induce either the enzymes or DNA synthesis. In submandibulectomized mice, although increases in the enzyme activities 8 h after injection of IPR were lower and they were significantly reversed by EGF, the activities at 12 h and the changes in polyamine levels at 8 and 12 h were almost the same as those in intact mice and were not affected by EGF treatment. These results obtained in vitro and in vivo suggest that EGF participates in the maximal response of IPR-dependent DNA synthesis but is not involved in the change of polyamine synthesis induced by IPR in murine parotid glands.

Adenosylmethionine Decarboxylase↗
PubMed1986

Comparative effects of nicardipine, a new calcium antagonist, on size of myocardial infarction after coronary artery occlusion in dogs.

To examine whether nicardipine, a dihydropyridine derivative, limits size of myocardial infarction, and to compare the protective effects of nicardipine administered before and early and late after coronary artery occlusion, 99mTc-labeled albumin microspheres were injected into the left atrium during 5 min temporary coronary artery occlusion to determine the extent of the hypoperfused zone (the area at risk). The coronary arteries were then reperfused for 45 min before 6 hr permanent coronary artery occlusion. Fifteen minutes before permanent occlusion, dogs were randomly assigned to a control group (n = 11), a pretreatment group (n = 9), which received at this point 10 micrograms/kg of nicardipine as a loading dose followed by a continuous infusion of 8 micrograms/kg/hr for 6 hr, an early treatment group (n = 9), in which nicardipine treatment was initiated 15 min after occlusion, or a late treatment group (n = 8), in which nicardipine administration was delayed for 3 hr. Six hours after coronary artery occlusion, the hearts were excised and the left ventricle of each was cut into 3 mm thick slices and stained with triphenyltetrazolium chloride. The extent of myocardial necrosis was measured by planimetry of the unstained areas. Thereafter, the same slices were autoradiographed and the extent of the hypoperfused zone was measured by planimetry of the "cold spot." The extent of the hypoperfused zone was identical among the four groups. In the control group, the ratio of the extent of myocardial necrosis to the extent of the hypoperfused zone was 95.8 +/- 3.8% (mean +/- SEM). However, it was significantly smaller in the pretreatment group (59.9 +/- 13.3%, p less than .05) and the early treatment group (49.0 +/- 10.6%, p less than .01) than in the control group. In the late treatment group, this value was not different from that in the control group (86.5 +/- 7.1%). There was a close inverse correlation between reduction of infarct size and the extent of the hypoperfused zone in the pretreatment and early treatment groups. Thus, nicardipine administered before or early after coronary artery occlusion limited infarct size by 37% to 49%, whereas when administration was delayed for 3 hr infarct size was not reduced. Furthermore, nicardipine had more striking effects on the ischemic myocardium of dogs with small hypoperfused zones than on that of dogs with large hypoperfused zones.

Animals↗
PubMed1986

The effect of beta-endorphin on biogenic amines, insulin, and glucagon levels in the hepatic portal circulation of normal and pancreatectomized dogs.

The effect of peak concentrations of beta-endorphin on hepatic portal and peripheral levels of plasma catecholamines, free serotonin, glucose, insulin, and glucagon was studied in trained, conscious, normal adult dogs fitted with an indwelling portal catheter. An injection of synthetic human beta-endorphin (20 micrograms/kg BW) into a cephalic vein produced a significant rise in the portal concentration of dopamine, norepinephrine, and epinephrine. The rise was accompanied by a reduction of portal free serotonin levels. The changes were not seen in the peripheral circulation. No appreciable changes in plasma insulin, glucagon, and glucose concentrations were noticed either in the hepatic portal or in the peripheral circulation. The response of the biogenic amines to beta-endorphin was abolished by pretreatment with Naltrexone (1 mg/kg BW). A dose of somatostatin antiserum given before beta-endorphin did not alter the biogenic amine response to the opioid peptide. When beta-endorphin was administered to pancreatectomized dogs devoid of exogenous and endogenous insulin supply, the biogenic amine response remained virtually the same as in normal intact dogs. It is concluded that in the dog a pulse of beta-endorphin causes profound alterations of splanchnic biogenic amine concentrations that are independent of the ambient levels of insulin, somatostatin, and pancreatic glucagon.

Amines↗
PubMed1986

Sympathetic nerve activity, plasma renin activity and water-sodium balance in obese patients with essential hypertension.

Studies were conducted to evaluate the role of water-sodium metabolism on the hypertensive mechanisms in obese patients with essential hypertension (EHT). The obesity index correlated positively with the mean arterial pressure, plasma volume, extracellular fluid volume or total exchangeable sodium, and negatively with plasma noradrenaline concentration or plasma renin activity in EHT. Hypotensive effects of sodium restriction (Na 35 mEq, K 75 mEq) or the natriuretic response to infused dopamine (3 micrograms/kg/min) was remarkable in obese EHT. Fractional excretion of sodium (FENa), which reflects the renal tubular reabsorption of sodium, was significantly lower in obese EHT than that in non-obese or mildly obese EHT. Urinary excretion of free dopamine (UDA) had a positive relationship with simultaneously measured urinary excretion of sodium or FENa. In addition, UDA correlated positively with the obesity index in patients whose weight was under 115% of the ideal weight. On the contrary, the relation between the two parameters was significantly negative in patients whose weight was over 115% of the ideal weight. These findings suggest that the expansion of body fluid volume and sodium, which might result from the blunted natriuretic ability, at least in part, due to an attenuation of the renal dopaminergic activity, play an important role of the hypertensive mechanisms in obese EHT.

Adult↗
PubMed1986

Immunobiological and biochemical characterization of solubilized rat gliosarcoma cell tumor-associated transplantation antigens.

Tumor-associated transplantation antigen (TATA) was solubilized with n-butanol from rat gliosarcoma cells (T-9). Under the conditions used for the solubilization of TATA, the viability of T-9 cells was maintained above 85%, suggesting that the contamination of TATA with cytoplasmic protein is minimal. Normal Fischer rats were treated with 500 micrograms of n-butanol extract and inoculated with 2 X 10(6) viable T-9 cells. At 8 weeks after the inoculation of viable tumor cells, the tumor diameter was significantly smaller than that in control untreated rats. Rats treated with 770 micrograms of n-butanol extract from T-9 cells were inoculated with 1 X 10(7) syngeneic FTL-13 thymic lymphoma cells or T-9 cells. The rats rejected the T-9 cells, whereas the FTL-13 cells grew gradually until the host died, indicating that the n-butanol extract from T-9 cells contained T-9 cell-specific TATA. The n-butanol extract was characterized by chromatographic separation on a TSK gel G3000SW gel filtration column and a Mono Q anion exchange column with the fast protein liquid chromatography system (FPLC). The TATA of T-9 cells was found to have a molecular weight of approximately 40,000-70,000 and was eluted at 0.6-0.9M NaCl from the Mono Q column. The cellular mechanisms responsible for the rejection of T-9 cells in the rats treated with the n-butanol extract were also examined. Adoptive transfer and in vitro experiments demonstrated that helper T cells for the generation of cytotoxic T lymphocytes were generated in the rats treated with n-butanol extract.

Animals↗
PubMed1986

[Postoperative chemotherapy of pathological stage I non-small cell carcinoma of the lung].

Between August 1982 and February 1985, 13 patients with pathological stage I non-small cell lung cancer received postoperative chemotherapy with ACNU, ADM and 5-FU. Nine patients had squamous cell carcinoma, two adenocarcinoma, and two large cell carcinoma. All patients were alive in August, 1985, but four of them had recurrent disease. The site of recurrence was the brain in three and the contralateral lung in one. Of these four patients, three had t2n0(-) p0 squamous cell carcinoma and one t1n0(-) p1 large cell carcinoma. In a control group consisting of six squamous cell carcinoma and six adenocarcinoma, recurrence occurred in one patient with t1n0(-) p0 squamous cell carcinoma. Although the treated group had unfavorable conditions of cell type and tumor size, there was no evidence that this combination chemotherapy could control recurrence of the tumor under these conditions.

Adenocarcinoma↗
PubMed1986

[The effects of neocarzinostatin on superoxide production by monocyte-derived macrophages].

Monocyte-derived macrophages (M phi) from cancer patients injected with low doses of Neocarzinostatin (NCS, 500 units/day, three times a week) 12 times produced significantly more superoxide (O2-) than controls. Lymphocyte functions, such as PHA response, surface marker and serum IAP, before and after NCS injections were the same. M phi from normal persons cultured with NCS (0.4 microgram/ml) for three days produced more O2- than controls, but those cultured with rINF gamma did not. These results suggest that the increased O2- production of M phi from patients taking low doses of NCS may be due to the direct action of NCS on the M phi.

Antibiotics, Antineoplastic↗
PubMed1986

[Combination chemotherapy and radiotherapy in small cell carcinoma of the lung].

Thirty-nine patients with small cell carcinoma of the lung were treated sequentially with induction chemotherapy, radiotherapy and then maintenance chemotherapy. Induction chemotherapy consisted of two regimens, cyclophosphamide, vincristine, methotrexate (COM) and adriamycin, ACNU, vindecine (ANV) given by randomization. Radiotherapy was given for patients with limited disease (LD) as a rule. After radiotherapy the drugs used for maintenance chemotherapy were alternated and reduced in dose. Eighteen patients were treated with a COM-ANV sequential combination and sixteen patients were treated with an ANV-COM combination. Thirteen patients had limited disease (LD) and eleven patients had extensive disease (ED). Of 12 patients with LD treated with COM-ANV therapy, 9 patients (75%) responded with 3 (25%) complete responses. Of 11 patients with LD treated with ANV-COM therapy, 9 patients (81.8%) responded to the therapy. According to disease extent, response rate was 82.6% for LD and 54.5% for ED. The median survival times were 9 months for patients with COM-ANV therapy and 12 months for those with ANV-COM therapy. Also, the median survival time was 15 months for LD patients and 5 months for ED patients. Major toxicities in ANV therapy were anorexia, nausea, and myelosuppression, and were more frequent than with COM therapy. These results showed no clear evidence of superiority in either the COM-AMV or ANV-COM regimen.

Adult↗
PubMed1986

Partial purification of C-C36 tumor rejection antigen molecules commonly expressed on syngeneic murine colon tumors, C-C36 and C-C26.

The tumor-specific transplantation antigens (TSTAs) of BALB/c mouse colon tumor C-C36 were characterized by gel filtration (TKS-gel FPLC), ion exchange chromatography (Mono Q FPLC) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. The cell surface antigens were solubilized noncytolytically with 2.5% n-butanol. It was demonstrated that the C-C36 antigens responsible for tumor rejection activity against C-C36 cells had a molecular weight of less than 200,000, and were eluted at 0.4-0.5M NaCl. On the other hand, the cross TSTAs expressed on C-C26 cells were eluted 0.2M NaCl. SDS-PAGE analysis of the partially purified antigens showed that the C-C36 TSTAs had four bands corresponding to molecular weights of 75,000, 68,000, 60,000 and 40,000. In contrast, the cross TSTAs expressed on C-C26 cells gave several major bands corresponding to 110,000, 94,000, 60,000 and 38,000, in addition to faint bands of 75,000 and 68,000. These results indicate that, although the partially purified C-C36 and C-C26 colon tumor antigens inducing rejection of C-C36 tumor challenge in syngeneic hosts showed differences in the ionic strength at which they were eluted, there are three common molecules with molecular weights of 75,000, 68,000 and 60,000, suggesting that these common molecules might be the tumor antigens responsible for the C-C36 colon tumor rejection.

Animals↗
PubMed1986

Specific cytotoxicity of a long-term cultured T-cell clone on human autologous mammary cancer cells.

We established an autologous specific T-cell killer clone, TcHMC-1, that has been cultured and has retained its function for over 1 year. TcHMC-1 and target cells (HMC-1-8) were derived from the metastatic pleural effusion of a patient with mammary carcinoma. At culture initiation, pleural exudative lymphocytes (PLEL) already demonstrated a high cytotoxic activity against uncloned HMC-1 breast tumor cell targets but not against autologous fibroblasts and K562 targets, and phenotypically these cells showed 100 and 90% reactivity with OKT3 and OKT8 monoclonal antibodies, respectively. However, at the early phase of cultivation under interleukin 2, PLEL had a relatively high cytotoxicity against some allogeneic tumor cells. Furthermore, the longer these PLEL were cultured with interleukin 2 and stimulated with MMC-treated HMC-1, the less cytotoxic activity of PLEL against HMC-1 targets became. We then cloned PLEL as well as HMC-1 tumor cells, and an autologous pair of TcHMC-1 and a target cell clone, HMC-1-8, was successfully obtained. TcHMC-1 showed more than 60% specific cytotoxicity against HMC-1-8, and it was confirmed, using cold target inhibition assays, that TcHMC-1 did not demonstrate nonspecific cytotoxicity against allogeneic targets as well as the natural killer cell activity. Moreover, we examined the in vivo action of TcHMC-1 against HMC-1-8 cells by the Winn assay using nude mice. The data showed that s.c. injections with a mixture of TcHMC-1 and HMC-1-8 clearly resulted in a failure of tumor development in the nude mice even 12 weeks after injections, whereas mice given injections of HMC-1-8 and allogeneic T-lymphocytes cultured with interleukin 2 developed tumors. The autologous pair of a killer T-cell clone and tumor line could be very useful for future investigations of the specific destruction of autologous tumor cells by cytotoxic T-lymphocytes, including analysis for tumor-specific antigens possibly of rejection type and clonotypic T-cell antigen receptors.

Antigens, Neoplasm↗