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Biomedical subjects

T Okawa

Publications and source records attributed to T Okawa.

At least 73 records · Page 4Linked to original sources

Radiotherapy for superficial esophageal cancer.

PURPOSE: The results of definitive radiotherapy for superficial esophageal cancer is presented. METHODS AND MATERIALS: Twenty-one patients with superficial squamous cell carcinoma of the esophagus were treated by definitive radiotherapy with megavoltage x-rays in Tokyo Women's Medical College from 1975 to December 1990. Eight patients refused surgery and 13 patients were considered to be unsuitable for surgery due to advanced age or morbid conditions such as severe pulmonary dysfunction, myocardial infarction, liver cirrhosis, and other cancer. Radiotherapy was performed using 1.8-2.2 Gy fraction dose, 5 times a week and with a total dose of 50-76 Gy/5-7 weeks (median; 70 Gy). Three patients received intraluminal radiotherapy in addition. Combined chemotherapy was performed in four cases, and three cases received it before radiotherapy and one case after radiotherapy. RESULTS: Overall survival rate was 40.8%, and the cause-specific 5-year survival rate was 61.7%. The 5-year survival rate of the group with morbid conditions was 17.5%, but that of the group without morbid conditions was 60.6%. Seven patients developed recurrence (primary site: 3, lymph nodes: 3, lung: 1) and one patient revealed multicentric cancer of the hypopharynx with wide submucosal spread of the esophagus at 28 months after radiotherapy. No patient developed severe side effect due to radiotherapy. CONCLUSION: Definitive radiotherapy with or without chemotherapy can be applied as an alternative therapy to surgery for superficial esophageal cancer, even for the operable patients under good general condition.

Aged↗

Histatin as a synergistic stimulator with epidermal growth factor of rabbit chondrocyte proliferation.

Histatin 5 dose-dependently increased DNA synthesis in rabbit costal chondrocytes in culture. The level of DNA synthesis was stimulated by histatin 5 to about 4 times that of the control. The combination of histatin 5 and epidermal growth factor (EGF) increased the DNA synthesis to about 40 times that of the control while EGF alone stimulated it 15-fold, indicating synergistic stimulation by both factors. Enzyme-linked immunosorbent assay using anti-histatin 5 demonstrated that human serum contained histatin-like substances. These findings suggest that histatins play an important role in chondrocyte proliferation, presumably as a physiological modulator of the action of EGF.

Adult↗

The peritoneal equilibration test variables in pediatric CAPD patients.

The peritoneal equilibration test (PET) is generally accepted as a valuable tool in individualizing continuous ambulatory peritoneal dialysis (CAPD) treatment schedules in adults. However, the classification of peritoneal permeability as described by Twardowski is not available for children due to differences in peritoneal transport abilities. In this paper, we report the results of the PET for 20 patients aged from 1.5 to 24 years (mean 10.3 years), who started CAPD therapy at age 0-15 years, using Twardowski's standardized technique. D/P creatinine (dialysate to plasma ratio of creatinine at 4 h), D/D0 glucose (the ratio of dialysate glucose at 4 h dwell time to dialysate glucose at 0 dwell time), and the residual volume (RV) in the abdominal cavity were calculated. The mean and standard deviation values for D/P creatinine and D/D0 glucose were of a higher permeability level than those reported in Twardowski's data. Furthermore, a significant correlation of creatinine and glucose with fluid drainage ability of the peritoneum were observed. A large amount of RV (425 +/- 125 mL/m2) was detected in the patients' peritoneal cavity and this had a significant correlation with dialysate leak occurrences. The authors suggest that the RV would be an indicator for leaks and especially latent leaks. The cause of a large RV is unknown, but there is a probability that drainage volume and transport rates of metabolites decrease because the concentration of the instilled dialysate is immediately diluted by a large RV within the peritoneum.

Adolescent↗

Effect of LC9018 combined with radiation therapy on carcinoma of the uterine cervix. A phase III, multicenter, randomized, controlled study.

BACKGROUND: The failure rate with radiation therapy alone for Stage III cervical cancer is quite high, and therefore other modalities are being pursued as adjuvants to radiation therapy in hopes of improving the results. METHODS: A randomized, controlled, comparative study on the efficacy and safety of radiation therapy combined with LC9018 (a biologic response modifier prepared from heat-killed Lactobacillus casei YIT9018) was conducted using 228 patients with Stage IIIB cervical cancer. RESULTS: LC9018 enhanced tumor regression (P < 0.1) by radiation after both 30 Gy of external radiation and at the completion of radiation therapy. The combination therapy also prolonged survival and the relapse-free interval (P < 0.05) compared to radiation alone. Analysis of survival using the Cox proportional hazard model indicated that use of LC9018 was a significant factor related to survival duration. Major side effects of combined LC9018 included fever and skin lesions at the injection site, but no severe symptoms were noted. Radiation-induced leukopenia was significantly less severe (P < 0.05) in the LC9018-combined group than in the radiation-alone group, suggesting that this agent might help to prevent leukopenia during radiation therapy. CONCLUSIONS: LC9018 was shown to be an effective agent for adjuvant immunotherapy when combined with radiation therapy.

Adjuvants, Immunologic↗

The influence of prostaglandins on the contractile response to electrical field stimulation in rabbit myometrial and cervical smooth muscles.

Indomethacin (10 microM) significantly reduced the contractile responses to electrical field stimulation (EFS) in the non-pregnant myometrium (5-50 Hz by an average of 25.7%) and the pregnant myometrium (30-50 Hz by an average of 16.5%). On the other hand, it significantly increased the contractile responses of the cervix in non-pregnant (2.5-30 Hz by an average of 21.5%) and pregnant (2.5-10 Hz by an average of 12.5%) muscular strips. Prostaglandin (PG) E2 (0.1-1000 nM) strongly and PGI2 (0.1-1000 nM) slightly and dose-dependently inhibited the contractile response to EFS of the non-pregnant cervical muscle, but not of the myometrium. In the pregnant uterus, the contractile responses of the cervical muscle were similar to those of the non-pregnant cervix, while the response of the myometrium was increased significantly and dose-dependently by the application of PGE2 or PGI2.PGF2 alpha (1000 nM) significantly increased the contractile response of the myometrium but not cervical muscle to EFS in the pregnant rabbits. In non-pregnant muscles, the contractile responses of the myometrium and cervical smooth muscle to EFS were not influenced by the treatment with PGF2 alpha.PGE2 (0.1-1000 nM) also inhibited the contractile response to direct muscle stimulation, but the inhibition was significantly less than that of the response to indirect stimulation. PGI2 slightly inhibited the contractile responses to both indirect and direct stimulation. These findings indicate that PGE2, PGI2 and PGF2 alpha increase the contractile response of pregnant myometrium to EFS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Oxytocin, PGE2 and PGF2 alpha stimulate the production of inositol phosphates in the rabbit myometrium.

Phosphoinositide breakdown is thought to be important in regulating a variety of transmembrane signal transduction in the action of oxytocic agent during uterine smooth muscle contraction. We investigated the effects of oxytocin and prostaglandins (PGE2 and PGF2 alpha) on phosphoinositide hydrolysis in the myometrium taken from non-pregnant and pregnant rabbits by measuring the accumulation of total inositol phosphates (IP). Oxytocin strongly, and PGE2 and PGF2 alpha slightly but significantly, stimulated IP production in both the non-pregnant and pregnant myometria. Oxytocin more markedly accelerated the IP production in pregnant myometrium than in non-pregnant myometrium. However, IP production stimulated by PGE2 and PGF2 alpha was much the same in non-pregnant and pregnant myometria. The amount and time course of the increase in the production of the total IPs by oxytocin are quite different from those by PGs. It seems that the mechanism by which oxytocin stimulates phospholipase C is different from that of the PGs. It is suggested that transmembrane signalling pathways of phosphoinositide hydrolysis play an important role in the each mechanism.

Animals↗

Pharmacological characteristics of contractile responses of rabbit uterine cervices to electrical field stimulation.

The pharmacological characteristics of contractile responses to electrical field stimulation (EFS) of uterine cervical muscular strips taken from non-pregnant and pregnant rabbits were investigated, in vitro. The contractile responses to EFS of both non-pregnant and pregnant muscular strips were markedly depressed by treatment with prazosin 1 microM, while the responses were only slightly depressed by treatment with atropine 1 microM. Propranolol 1 microM did not affect the responses. Guanethidine 10 microM and tetrodotoxin (TTX) 10 microM also depressed the contractile responses to EFS of both non-pregnant and pregnant muscular strips. However, the depressive effects of the latter 2 drugs were more marked in non-pregnant muscular strips than in pregnant ones. These findings indicate that the uterine cervical smooth muscle is predominantly innervated with adrenergic excitatory nerve fibers. The cholinergic innervation in uterine cervical smooth muscle seems minor. Furthermore, during pregnancy, a TTX-resistant, non-adrenergic, non-cholinergic component might increase the contractile response of uterine cervical smooth muscle to EFS.

Animals↗

Prostaglandins biosynthesis in the rabbit uterine cervix at various stages of pregnancy.

The accumulation of prostaglandins (PGs: 6-keto PGF1 alpha, PGE2, PGF2 alpha and TXB2) elicited by A-23187, a Ca(2+)-ionophore, was studied in the uterine cervical tissue taken from non-pregnant and pregnant (10th, 20th and 30th day of pregnancy) rabbits in vitro. At every stage of pregnancy, the accumulation of PGs levels increased as follows; 6-keto PGF1 alpha, PGE2, PGF2 alpha and TXB2. Biosynthesis of each began to increase from the 20th day of pregnancy, and was significantly elevated at the 30th day. Especially, 6-keto PGF1 alpha and PGE2 were remarkably higher than PGF2 alpha and TXB2 at term, and so they are thought to play a more important role in cervical dilation and ripening than the other PGs. Six-keto PGF1 alpha was significantly elevated on the 20th day, when other PGs had not yet began to increase. It is thus conceivable that PGI2 plays an important role in the predispositing of cervical ripening.

Animals↗

[Multi-center cooperative phase II study of combined infusion of PJ-203 (degradable starch microspheres) into hepatic artery in metastatic liver cancer].

In the present multi-center cooperative phase II study, in which 16 institutions participated, PJ-203 and mitomycin C were concomitantly infused into the hepatic artery of patients with metastatic liver cancer and the tumor response and safety of the combined therapy were examined. Of 81 patients treated with PJ-203, 52 patients were complete cases in which bidimensionally measurable lesions could be assessed for anticancer effect in accordance with the Direct Evaluation Criteria of Chemotherapy. The number of treatments given to the complete cases until the assessment of therapeutic effect ranged from 1 to 11 times, with the mean of 3.1 times. The overall response rate was 48.1% (25/52). The response rate for each primary lesion was 68.8% (11/16) for stomach cancer, 40.7% (11/27) for colorectal cancer and 33.3% (3/9) for other types of cancer including the gallbladder. The 25 patients with CR or PR, a 50% decrease in tumor size was confirmed after the treatment ranged from 1 to 5 times, with the treatment periods of 2 to 3 weeks. Adverse reactions were found in 56 (69.1%) out of 81 patients assessed for safety. Relatively frequent symptoms were pain in 49.4% (40/81), nausea and vomiting in 33.3% (27/81), fever in 30.9% (25/81) and anorexia in 6.2% (5/81). Principal abnormal laboratory values included a transient elevation of GOT (26.3%), GPT (22.5%), LDH (12.7%) and Al-p (8.8%). Blockade of blood flow could be observed by angiography when the amount of PJ-203 infused was in the range from 180 to 900 mg as degradable starch microspheres. The blood flow blockade could be observed most frequently at the amount of 600 mg (37.7%). The period attaining over 50% of tumor response in 25 complete cases was 42 days as a median. After the treatment was initiated in 81 patients, 50% survival duration and one-year survival rate averaged 277 days and 35.7%, respectively. The corresponding figures for each primary cancer were 419 days and 51.0% for patients with liver cancer metastasized from colorectal cancer, against 239 days and 11.8% for those with liver cancer metastasized from stomach cancer.

Adult↗

[Comparative clinical study in metastatic liver cancer between intra-arterial infusion of mitomycin C alone and intra-arterial infusion of mitomycin C combined with PJ-203 (degradable starch microspheres)].

In the present comparative study, we examined an intra-arterial chemotherapy combined with PJ-203 in 60 patients with liver cancer metastasized from gastrointestinal cancer, using an intra-arterial chemotherapy alone as the control. Sixty patients who had been registered by telephone contact were allocated to groups either treated with the intra-arterial chemotherapy alone or with PJ-203 combined, 30 patients each. Mitomycin C was used as the anticancer drug and given at the dose of 8mg/m2 per time. The dose of PJ-203 was 600 +/- 300 mg as degradable starch microspheres. A significantly higher response rate (CR + PR/complete cases) of 54.5% (p = 0.021) was noted in the PJ-203 combined group, as compared to 20.0% for the control group. The 50% survival duration was 282 and 214 days for the PJ-203 combined group and control group, respectively, with no significant difference being noted between the two groups. Principal adverse reactions such as pain, gastrointestinal symptoms and fever were statistically more frequent (p < 0.01) in the PJ-203 combined group than in the control group. Among the abnormal laboratory values, the incidence of decreased leukocytes was significantly lower (p = 0.022) in the PJ-203 combined group than in the control group. One of the patients concomitantly treated with PJ-203 died of drug-induced hepatitis, which was probably attributed to mitomycin C. However, overall utility assessment was significantly better (p = 0.002) in the PJ-203 combined group.

Adult↗

[Protooncogene c-myc amplification and cell cycle analysis in human malignant tumors].

As predictors of tumor response by radiotherapy, tumor with or without c-myc amplification and DNA histogram pattern were analyzed and evaluated for patients' prognosis. There was no relation between c-myc amplification and DNA ploidy pattern in this study. These factors also showed no relation to response rate and survival. But all of the tumors with c-myc amplification and aneuploid pattern exhibited a complete response by radiotherapy. The tumors with c-myc amplification and aneuploid pattern may be more radiosensitive than without amplification and diploid. These data suggested that c-myc amplification and ploidy pattern might be a predictive parameter before radiotherapy.

Cell Cycle↗

Experimental infection of cynomolgus and African green monkeys with human herpesvirus 6.

Cynomolgus and African green monkeys were inoculated with human herpesvirus 6 (HHV-6). An antibody response was first observed 10 days and 5 days after inoculation of cynomolgus monkeys and African green monkeys, respectively, and was detectable for the duration of the experiment (33 days). HHV-6 DNA was first detected by the polymerase chain reaction in mononuclear cells of one cynomolgus monkey and one African green monkey 10 days after virus inoculation, and in a total of three of four cynomolgus monkeys (75%) and four of five African green monkeys (80%) later after inoculation. Furthermore, HHV-6 DNA was detected in the lymph nodes and spleen of monkeys killed 33 days after virus inoculation. A rash was observed on the trunk of one African green monkey 13 days after virus inoculation, otherwise the infection was asymptomatic. When mononuclear cells from both groups of monkeys were cultured in medium containing concanavalin A and interleukin 2, and infected with HHV-6 in vitro, virus replication was observed. The data suggest that HHV-6 infects these species of monkey and that this system could be useful as an animal model of HHV-6 infection.

Animals↗

[Application and technique of breast conservative treatment of breast cancer].

In patients with breast cancer who had undergone breast conservative treatment involving lumpectomy, axillary lymph node dissection and irradiation, the surgical results and risk factors for remaining cancer foci in the conserved breast were investigated. This form of surgery was performed in 25 patients with T1,N0,-Ia,M0 breast cancer. The cut end of the resected specimen was histopathologically positive for cancer cells in 48% of the patients, but there has been no local or distant recurrence in any patient to date with a mean follow-up period of 17.2 months after surgery. In most breasts resected after lumpectomy, slight cancer foci remained in mammary glands at the sites within 1.0cm distant from the cut end. Extensive remaining cancer lesions were found among cases with advanced intraductal spread or central necrosis in the intraductal foci. The above findings indicate that breast conservative treatment by lumpectomy may result in histopathologically remaining cancer foci, although these can be controlled by irradiation therapy. However, application for this treatment requires much caution when severe intraductal spread or central necrosis is present in the intraductal foci, because extensive cancer foci may remain postoperatively in such cases.

Adult↗

[Conservative surgery and radiotherapy of early breast cancer].

Radiation dose-effect relationship is reviewed. In conservative treatment of early breast cancer, necessity of radiation is discussed and surgery with radiotherapy technique in our hospital is presented. Our procedures consist of lumpectomy which is removal of 1 cm of normal tissue containing primary breast cancer and complete axillary dissection and postoperative radiotherapy of 46 Gy with 9 Gy of electron boost. Since November 1987, 51 patients treated by this procedure have shown a good local control and a satisfactory cosmetic results. We can conclude that the positive aspects of radiotherapy in the management of conservative therapy for early breast cancer are overwhelming.

Breast Neoplasms↗

[Radiotherapy on the basis of quality of life].

Considering the relationship between tumor lethal dose and normal tissue tolerance: the therapeutic ratio, radiation oncologists have been performed the radiotherapy for cancer patient. The basic principle of radiotherapy is to have a good result (curability), to be tolerable in side effects and to have a comfortable life after radiation. Radiotherapy is the important strategy for an early stage of cancer with conserving the function and structure, and for an advanced or a recurrent stage of cancer with contributing to improve the quality of life. Recently, advantage of radiation tools and supportive care of cancer treatment, have been able to decrease the incidence of late injuries and complications. Radiotherapy must be planned on basis of considering therapeutic ratio and should be performed with optimum radiation in the multimodal treatment for cancer.

Humans↗

Biosynthesis of prostaglandins (PGs) and effect of PGs on C-AMP content in the rabbit uterine cervical tissue at term.

The effects of prostaglandins (PGs: PGE2, PGI2 and PGF2 alpha) on contractility, PGs production by A-23187 and C-AMP production by these PGs were studied in the rabbit uterine cervical tissue at term in vitro. PGE2 or PGI2 had an inhibitory effect on the contractility; the inhibitory effect of PGE2 was more potent than that of PGI2. On the other hand, PGF2 alpha had an excitatory effect on the contractility. The mean rate of 6-keto-PGF1alpha production by A-23187 was more remarkable than those of PGE2 and PGF2 alpha. The PGE2 production was the second highest among the three PGs. The C-AMP was significantly increased by PGE2 and PGI2. The increased C-AMP level induced by PGE2 was greater than that by PGI2. On the other hand, PGF2 alpha did not increase C-AMP. From these experimental results, it seems that the production of large amounts of PGE2 and PGI2 facilitates cervical dilatation during parturition, and suggests that C-AMP participates in the cervical dilatation elicited by both PGE2 and PGI2.

Animals↗