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Biomedical subjects

N Uchida

Publications and source records attributed to N Uchida.

At least 289 records · Page 16Linked to original sources

A new applicator utilizing distributed electrodes for hyperthermia: a theoretical approach.

We propose a new type of applicator for hyperthermia namely a Distributed Electrodes Applicator. Many electrodes are fixed on boli below which the patient is placed. A set of RF with optimized amplitudes and phases is supplied to the electrodes so as to minimize the ratio of SAR (specific absorption rate) in the fat layers to that in the central region of the patient. SAR patterns in a heated material were calculated using two-dimensional finite element method, and the results showed that the proposed applicator can heat the deep portions of the patient without excessive heating of the fat layers.

Electrodes↗

Protein kinase C activity in human gastric carcinoma.

Protein kinase C (PKC) is believed to play an important role in tumorigenesis, so we measured PKC activities of human gastric carcinomas and adjacent normal mucosae to elucidate its role for gastric carcinogenesis using PegTagtrade mark non-radioactive protein kinase C assay. The mean activities of microsomal PKC in carcinoma and normal mucosa were 449+/-179, 661+/-264 pmol/min/mg, respectively (p=0.001). Cancerous microsomal PKC activity decreased when the tumor was small, node-metastasis was negative, the depth of invasion was shallow and the histological type was differentiated. Our results suggested that PKC activity would be down-regulated in membrane of the early stage of gastric carcinoma.

Adult↗

Phospholipase D activity in human gastric carcinoma.

Growth factor-stimulated phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine, generating phosphatidic acid which may act as a second messenger during cell proliferation, therefore PLD is believed to play an important role in tumorigenesis. Thus we measured PLD activity in human gastric carcinoma to evaluate its role in gastric carcinogenesis. PLD activity was assayed by a unique transphosphatidylation reaction using microsomal fraction of 21 pairs of surgically resected human gastric carcinomas and adjacent noncancerous mucosas. The mean PLD activities in gastric carcinoma and adjacent noncancerous mucosa were 63.0 +/- 69.5, 44.2 +/- 60.1 pmol/min/mg, respectively (p < 0.01; Wilcoxon signed rank test). The mean ratio of PLD activity in gastric carcinoma and adjacent noncancerous mucosa was 1.63. This ratio was significantly higher in patients with larger tumors (> or = 5 cm) (p < 0.01; Mann-Whitney U-test). Our results indicate that the elevation of PLD activity plays an important role in the promotion of gastric carcinoma.

Adenocarcinoma↗

Enhanced antitumor efficacy of nedaplatin with 5-fluorouracil against human squamous carcinoma xenografts.

BACKGROUND: The antitumor efficacy of a combination of Nedaplatin (NDP) with 5-fluorouracil (5-FU) was evaluated using human squamous carcinomas in vivo. Because NDP was developed as a second generation platinum complex, we also compared the antitumor activity of NDP with 5-FU with that of Cisplatin (CDDP) with 5-FU. MATERIALS AND METHODS: 5-FU was injected daily for five days and either NDP or CDDP was injected once via the tail vein of mice implanted with KB3-1, OCC-1-JCK, LJC-1-JCK and Ma44 human squamous carcinomas. In some experiments, continuous administration of 5-FU using an osmotic pump was utilized. RESULTS: The sequential administration of 5-FU prior to NDP or CDDP (FN or FC therapy) resulted in enhanced inhibition of tumor growth in comparison with NDP, CDDP or 5-FU monotherapy against KB3-1, OCC-1-JCK and LJC-1-JCK squamous carcinomas. The combination of FN treatment was synergistic and as effective as that of FC treatment. FN treatment with continuous infusion of 5-FU using an osmotic pump, also led to enhanced tumor growth inhibition and prolonged survival against Ma44 squamous carcinoma. CONCLUSION: The results demonstrated the antitumor efficacy NDP with 5-FU against four human squamous carcinoma xenografts and suggested the clinical effectiveness of FN treatment.

Animals↗

Squamous cell carcinoma of the external auditory canal: two cases treated with high dose rate 192Ir remote afterloading system (RALS).

We report two cases of early-stage external auditory canal cancer treated by intracavitary irradiation with a high dose rate (HDR) 192Ir remote afterloading system (RALS) for preoperative treatment. A 6-Fr catheter for the HDR 192Ir remote afterloader, fixed by a plastic earplug, was inserted into the external auditory canal in two cases (case 1, T2N0M0; case 2, T1N0M0). The total intracavitary radiation dosages were 50 Gy (10 Gy/2 Fr/wk for 5 wks) for case 1, and 42 Gy (15 Gy/5 Fr/wk for 3 wks) for case 2. No external irradiation was given in either case. Surgical resection was performed in both cases, three to four weeks after irradiation. Histopathological examination confirmed the post-irradiation changes of necrosis, hyalinosis, and calcification, although vivid cancer cells remained. In preoperative irradiation of external auditory cancer, this method, although limited to treating early-stage cancers, may be a modality of choice for its efficacy and less severe side effects.

Brachytherapy↗

Enhancement by androgen of the angiogenic ability of androgen-responsive Shionogi carcinoma 115.

The effects of various steroids on the induction of angiogenesis by androgen-responsive Shionogi carcinoma 115 (SC115) were investigated by implanting a piece of a SC115 tumor tissue into a rabbit cornea together with a pellet containing each steroid (250 micrograms) and by examining neovascularization from the limbus. SC115 tumor tissues induced neovascularization in 42% corneas in the absence of steroids, and in 31, 63, 80 and 4% in the presence of estradiol-17 beta, progesterone, testosterone and dexamethasone, respectively. Only testosterone significantly increased the percentage of corneas with neovascularization, while dexamethasone significantly decreased it. Testosterone itself induced no neovascularization, and dexamethasone also inhibited neovascularization induced by acidic fibroblast growth factor. The present results suggest that androgen increases the secretion of an angiogenic factor(s) by an androgen-responsive SC115 tumor, while dexamethasone inhibits angiogenesis induced by the angiogenic factor(s).

Animals↗

Stimulation by estrogen and progesterone of the in vivo growth of transformed murine Leydig cells only at the limited early phase of growth.

B-1 F is a cell line established from estrogen-responsive murine Leydig cell tumor and maintained in vitro. We investigated the effects of steroid hormones on the growth of tumors produced by the inoculation of B-1 F cells into mice. When tumor tissues were transplanted into castrated male mice, injections of estradiol-17 beta (E2) or progesterone shortened the period before tumors became palpable, but did not affect the growth rates of tumors after tumors became palpable. Injections of E2 or progesterone from the time when tumors became palpable did not affect the growth of tumors, and the discontinuation of injections of E2 or progesterone during the middle growth phase showed no effect on the growth of tumors. E2 or progesterone also did not increase the mitotic indices of tumors after they became palpable. E2 and progesterone did not stimulate the proliferation of dispersed tumor cells in vitro. The present results suggested that steroid hormones might exert their actions only at the limited early phase of growth of transplanted steroid hormone-responsive tumors in vivo.

Animals↗

Real time sound spectral analysis for early detection of thrombosed Björk-Shiley standard disc valves.

Clinical usefulness of sound spectral analysis (SSA) in early detection of thrombosed Bjork-Shiley standard tilting disc prostheses (B-SP) was evaluated. Among a total of 365 B-SP, nine valves developed thrombosis. These included seven MVR and two AVR, and replacement of the affected valves was performed in all cases. Thrombus formation was localized at the minor strut in two cases in which the SSA demonstrated preoperative abnormalities of only opening clicks. In four cases, thrombus formation was noted at both minor and major struts, and the SSA showed abnormalities both on opening and closing clicks. In two cases with pannus formation, no abnormalities were found by SSA. As the thrombi were seen on the minor strut during surgery in all cases with thrombosed valves, the minor strut is considered as the preferred, and probably initial area of thrombus formation, and the diagnosis therefore could be made by abnormal findings on opening clicks. In conclusion, the SSA was found to be a useful diagnostic tool for early detection of thrombosis of B-SP, because the opening clicks of the tilting disc valves were often too low in amplitude for abnormalities to be detected by auscultation.

Adult↗

Development of an epicardial circulatory assist device.

The overall purpose of this project was to develop a circulatory assist device that could be used as a bridge to heart transplantation. Although heart muscle damage was one of the disadvantages with the original epicardial assist devices, as long as no bleeding occurs, such trauma would be of secondary importance in this particular application. The development of the proposed epicardial circulatory assist device (ECAD) was evolutionary in nature, with the second prototype design based on the lessons learned from that of the first. In vivo results from both phases of the project are reported. ECAD prototype 1 (ECAD-1) was composed of a flexible outer housing and two driving balloons. Fixation to the heart was adjustable for various heart sizes using Velcro fasteners. The design of the ECAD prototype 2 (ECAD-2) was based on the results of ECAD-1. Fixation to the heart was accomplished by suturing the outer housing onto the heart along the anterior descending artery and at the posterior atrioventricular groove. Each device was tested in five dogs. ECAD-1 was able to maintain the systemic circulation for 5 hours. However, unstable fixation and myocardial damage due to rubbing were the major problems. ECAD-2 passive effects on natural heart filling were acceptable. Under conditions of severe heart failure, a flow of more than 85% of control was obtained with a driving rate of 90-110 beats/min and 30% systole. The longest pumping was conducted for 8 hours. The ECAD was demonstrated to be a device useful in assisting the failing heart for short periods. Proper design will play a fundamental role in successful extended use.

Animals↗

Pharmacokinetic correlation between experimental and clinical effects on human non-small cell lung cancers of cis-diammineglycolatoplatinum (254-S) and cis-diamminedichloroplatinum.

We attempted to correlate the in vitro and in vivo antitumor activities of cis-diammineglycolatoplatinum (254-S), a novel platinum complex, and cis-diamminedichloro-platinum (CDDP) against the established culture cell lines and xenografts of human non-small cell lung cancer (NSCLC) with their clinical effects, based on the previous finding that the cytotoxicity of CDDP depends on the area under the curve (AUC). The concentration of 254-S and CDDP inhibiting the in vitro growth of 4 cultured NSCLC lines by 50% (IC50) was 0.82-7.8 and 0.53-4.2 micrograms/ml, respectively, showing a similar level. Of the 4 cell lines, only the most sensitive line, RERF-LC-AI, showed an IC50 close to a specific concentration (0.50 for 254-S and 0.32 micrograms/ml for CDDP) that reproduces in vitro the clinical AUCfree (24.8 and 5.34 micrograms-hr/ml) of the respective drugs. We treated 6 lines of human NSCLC xenografts implanted in nude mice with 254-S and CDDP at a particular dose (13.2 and 3.7 mg/kg) that is equivalent to the clinical doses with respect to the plasma AUCfree. 254-S and CDDP exhibited significant antitumor effects on 2 and 1 of the 6 lines, respectively. These in vitro and in vivo findings were considered to be relatively well correlated with the reported clinical response rates of 15-19% for 254-S and 14-15% for CDDP.

Adenocarcinoma↗

Synergy of the combination of nedaplatin with etoposide in murine and human lung carcinoma.

BACKGROUND: The combination of cisplatin (CDDP) and etoposide (ETP) has been shown to be an effective treatment for lung cancer. Nedaplatin (NDP) has been developed as a second generation plainum complex. Because of its superior antitumor activity and lower nephrotoxicity in comparison with CDDP, the antitumor effects of NDP in combination with ETP against murine and human lung cancer was investigated. MATERIALS AND METHODS: Lewis murine lung carcinoma, RERF-LC-AI, and Ma44 human lung cancer were used in this study. NDP (1/4 to 1 maximum to related dose; MTD) and CDDP (1/4 to 1 MTD) were administered once and ETP (1/32MTD) was administered daily for five days via the tail vein of mice. RESULTS: In the mice bearing Lewis lung carcinoma, a combination of NDP and ETP resulted in synergistically enhanced inhibition of tumor growth (Treated/Control ratio; T/C = 0.001) in comparison with either NDP or ETP alone (T/C = 0.12 for NDP, T/C = 0.13 for ETP), and prolonged survival (Increased Life Span; ILS% > or = 172) in comparison with either NDP or ETP alone (ILS% = 65 for NDP, ILS% = 54 for ETP). NDP showed a more potent combination effect with ETP than CDDP did for both growth inhibition and survival. This effect was confirmed in human lung cancer. Although body weight loss was enhanced by the combined treatment, it was tolerable. With regards to myelosuppression, no significant difference between NDP plus ETP and CDDP plus ETP was observed. CONCLUSION: These results suggest the superiority of a combination of NDP with ETP against CDDP with ETP as a clinical therapy for lung cancer.

Animals↗