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Biomedical subjects

T Inomata

Publications and source records attributed to T Inomata.

At least 163 records · Page 9Linked to original sources

Antitumor activity of methyl (5-fluoro-1H-2-oxo-4-pyrimidinyl beta-D-glucopyranosid)uronate against various experimental tumors.

The antitumor activity of a glucuronide of 5-fluorouracil, methyl (5-fluoro-1H-2-oxo-4-pyrimidinyl beta-D-glucopyranosid) uronate (FU-O-G), which is a 5-fluorouracil (5-FU) derivative with remarkably low toxicity, was studied. The antitumor activity of this compound was superior to those of 5-FU and 1-(2-tetrahydrofuryl)-5-fluorouracil (Tegafur, Ftorafur) in the treatment of transplantable tumors, not only 5-FU-sensitive tumors such as adenocarcinoma 755, lymphosarcoma LS-1, and plasmacytoma X5563, but also 5-FU-resistant tumors such as Lewis lung carcinoma and Walker carcinosarcoma 256. Furthermore, in the treatment of Lewis lung carcinoma, which responds poorly to 5-FU and Ftorafur, daily administration of FU-O-G at a dose of 400 mg/kg for 30 days produced a 92% increase in life span without marked loss of body weight, though short-term administration (such as 5 days) was barely effective. Thus, it appears that FU-O-G is an antitumor agent suitable for long-term administration. These findings correspond with the results of an enzymological study which showed selective activation of FU-O-G by beta-glucosidase in tumor cells and indicated that the compound is a marked form of 5-FU.

Animals↗

Incorporation of tritium into cell materials of Rhodopseudomonas spheroides from tritiated water in the medium under aerobic conditions.

When Rhodopseudomonas spheroides cells grown aerobically in the dark were incubated in medium containing tritiated water (THO), incorporation of T into the bacterial cell materials occurred under growth and no-growth conditions. The overall T incorporation under no-growth conditions was stimulated by vigorous aeration and was suppressed strongly in the presence of either 10(-3) M KCN or 0.3% HgCl2, indicating that the bulk of the incorporation might depend upon bacterial cell metabolism or respiration. 10 mug/ml chloramphenicol and 20 mug/ml rifamipicin slightly suppressed the T incorporation. The extent of T incorporation was proportional to the concentration of T in the medium. Accordingly, regardless of differences in the concentration of T in the medium, the maximum ratio of T content per hydrogen atom in the cell materials to that of THO in the medium was approximately 0.2 in non-growing cells and 0.5 in growing cells, whereas the value was 0.02-0.03 in cells incubated in medium containing KCN or HgCl2. The non-growing cells aerated in THO medium were lyophilized and fractionated by the modified method of Schneider. More than 40% of the total T incorporated into the cell materials was recovered in the cold PCA-soluble fraction, whereas the distribution of T into fractions solbule in ether-ethanol, hot PCA and alkali was 10 to 20% each. More than 75% of the T extracted in the cold PCA-soluble fraction was volatile. While the amounts of RNA and protein in the non-growing cells decreased on adding chloramphenicol or rifampicin, the distribution of T in these fractions did not change much. Our results on T incorporation into non-growing cells indicate that the major T incorporation into bacterial cell materials is independent of biosynthetic reactions using labeled precursors produced by the assimilation of T into metabolites, but presumably depends on energy-linked conformational changes of macromolecules.

Aerobiosis↗

Ferric ammonium citrate-cellulose paste for opacification of the esophageal lumen on MRI.

OBJECTIVE: A new ferric ammonium citrate-cellulose mixture for use in MRI of the esophagus was evaluated for its ability to opacify the esophageal lumen. MATERIALS AND METHODS: Thirty-two patients with esophageal disorders and ten patients with normal esophagus undergoing MRI at 1.5 T were given approximately 100 ml of the newly developed high-viscosity esophageal contrast preparation. Moreover, six of the patients with esophageal cancer were subjected to a second examination after radiation therapy. A total of 48 MR imagings were performed. RESULTS: Of the patients examined, successful esophageal opacification, graded as excellent, was obtained in 84.2, 78.9, and 57.9%, of the sagittal, axial, and coronal images, respectively. In cases of extrinsic disease involving the esophagus the contrast medium administration allowed the easy differentiation of the esophagus from adjacent mass lesions and proved very useful in identifying displacement and compression. In cases of esophageal carcinoma the contrast medium administration assisted in the measurement of wall thickness and length of the lesion as well as in the identification of the site of origin of the tumor. CONCLUSION: The results indicate that this product effectively opacifies the esophageal lumen in the majority of patients. We found that it is easy to use, is well tolerated, and does not produce artifacts.

Artifacts↗

New barium paste mixture for helical (slip-ring) CT evaluation of the esophagus.

Successful opacification of the lumen of the esophagus with cancer or paraesophageal diseases has not yet been fully achieved. Therefore, we have recently adopted a new method for complete and continuous opacification of the whole thoracic esophagus using our newly developed oral contrast agent with a helical (slip-ring) CT scanner. The agent consists of 3.6 (wt/vol)% carboxy-methyl cellulose sodium paste containing 2 (wt/vol)% barium sulfate. The results indicate that almost complete and continuous opacification of esophageal lumen was achieved. Our new method of esophageal CT is easy to perform and was well tolerated by patients, being therefore ideal for routine examinations.

Administration, Oral↗

New barium paste mixture for helical (slip-ring) CT evaluation of rectal carcinoma.

We describe a new method for complete opacification of the rectum using helical CT and a newly developed anal contrast agent. Rectal cancers were easily identified in all of the 21 patients examined, and diagnostic accuracy in detecting local invasion was 94%. Our method of rectal CT is easy to perform and well tolerated.

Barium Sulfate↗

Ir gene for bovine insulin in the rat maps to RT1.B beta.

The genetic control of the immune response to bovine insulin (BI) in the rat was investigated. As a result of experiments utilizing two intra-MHC recombinant rats and of blocking experiments with monoclonal antibodies against MHC class II antigens, an immune response gene for BI in the rat could be mapped to the RT1.B beta locus.

Animals↗

Sequential alteration of proto-oncogene expression in liver, spleen, kidney and brain of mice subjected to whole body irradiation.

Reverse transcription polymerase chain reaction (RT-PCR) was performed to evaluate the sequential alteration of proto-oncogene mRNA expression in liver, spleen, kidney and brain of mice after whole body irradiation (WBI). The mRNAs investigated in this study were Fas, c-fos, c-myc. bcl-2, and p53, and glyceraldehyde-3-phosphate dehydrogenase mRNA was employed as internal control. C3H/He mice aged 9-10 weeks were exposed to WBI of 7 Gy using a cobalt-60 teletherapy unit, without anesthesia, and sacrificed before and 0.1, 0.5, 1, 2, 3, 6, 12, 24, 48 and 96 h after irradiation. Their liver, spleen, kidney and brain were taken and immediately stored in liquid nitrogen until ready for RT-PCR. Each specimen was homogenized to extract RNA for conventional RT-PCR. The liver of mice administered 7 Gy of WBI revealed no significant changes in the expression of each of the mRNAs examined. In the spleen, c-fos mRNA expression decreased at 2 h following irradiation, and increased remarkably thereafter. In the kidney, no significant change in the expression of each mRNA was shown. In the brain c-fos mRNA expression decreased 1-24 h after irradiation, and showed a recovery thereafter. The remarkable differences in the sequential changes of c-fos mRNA expression following irradiation between each organ revealed by the present experiment may be an important aid in determining the tissue-specific radiosensitivity to ionizing radiation. Further investigations are, however, needed to clarify the signal transduction mechanisms which are mediated by the expression of these proto-oncogenes in each tissue following irradiation.

Animals↗

Changes of mutant-type p53 expression in squamous cell carcinoma of the head and neck during radiation therapy and its clinical significance: comparison of an immunohistochemical method and PCR-SSCP assay.

P53 has been reported to be one of tumor suppressor genes that play a major role in signal transduction following many kinds of stresses, including ionizing radiation. Changes in p53 expression during radiation therapy in tumor tissues have not yet been reported. We determined whether radiotherapy changes p53 expression in human squamous cell carcinomas of the head and neck, and established the possible correlations between p53 expression and the therapeutic effects of radiation therapy. 30 patients with tumors of the oral cavity, oropharynx, and maxillary sinus were examined, and all the tumors were confirmed as squamous cell carcinomas. Biopsies were performed on the cancer tissues before treatment and at doses of 4, 10, and 20 Gy of radiotherapy, and the specimens were preserved in liquid nitrogen for further examination. Samples were immunohistochemically stained using streptoavidin-biotin peroxidase method and a monoclonal antibody against p53 (Ab-3, mutant type). For all the samples p53 PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) assays were performed. 14 of the 30 patients with squamous cell carcinomas showed expression of p53 in their tumor cells before and/or at 4 Gy or 10 Gy of radiotherapy. Eleven of the 14 tumors showed high radiosensitivity. Results of the p53 PCR-SSCP assays revealed mutations of p53 in 13 of 30 patients examined, and percentages of mutated p53 DNA varied at radiation doses of 4 Gy and 10 Gy. Ten of 12 patients with mutated p53 in their tumors showed decreased percentages of mutated p53 DNA during radiotherapy. The relationship between the immunohistochemical findings and the antitumor effect of a radiation dose of 20 Gy was examined on the correspondent hematoxylin-eosin sections. In patients whose p53 expressions in tumor cells were grades + or ++ or before radiotherapy and/or at 4 Gy of radiotherapy, the tumors responded significantly well to radiation therapy but the patients responded with significantly unfavorable clinical courses. The high radiosensitivity of squamous cell carcinomas in our samples could be explained by an overexpression of mutant type p53 in the tumor cells, and these mutant type p53-positive tumor cells possibly showed radioresponsiveness.

Adult↗

Conservation treatment intensified with tamoxifen and CAF chemotherapy for subareolar breast cancers.

Formerly, patients with subareolar breast cancers have not been good candidates for breast-conservation treatment (BCT) in Japan. However, recently it was reported that patients with subareolar cancers were good candidates for this treatment. In order to improve both cosmetic results and survival rates, we performed BCT for 27 patients with subareolar breast cancers following pre-operative CAF chemotherapy and tamoxifen administration. From August 1989 to June 1998, we performed BCT for 200 out of 206 patients who visited our hospital with the desire of breast-conservation. Of these patients, 27 presented with tumors within 2 cm of the nipple areolar complex. For 26 of these 27 patients, breast-conserving surgery was performed following two to four times of CAF chemotherapy, and another one patient did not undertake any surgical resection. Following the surgery, patients were treated with radiation therapy to the intact breast and ipsilateral axilla to a total dose of 4,400 cGy with electron conedown to a total dose of 5,300 cGy. Their primary tumors were at T4bN0 in 1 case, T2N1b in 5 cases, T2N0 in 18 cases, and T1cN0 in 3 cases. Tamoxifen was administered to all the patients. CAF chemotherapy was performed six times for stage I patients, and eight times for stage II patients in total. For one patient with direct tumor invasion to the nipple, intraarterial infusion chemotherapy was performed following radiation therapy and CAF chemotherapy, without any surgical resection. For another 26 patients, breast-conserving surgery was performed, and 5 of them underwent lumpectomy under local anesthesia on an outpatient basis. For these 26 patients, the microscopic surgical margin was positive for 8 patients, close for 6 patients, negative for 10 patients, and unknown for 2 patients. All patients are alive with no evidence of disease after a follow-up of approximately 47 months on average, and all of their cosmetic results are estimated as excellent or good. It is concluded that BCT intensified with preoperative CAF chemotherapy and tamoxifen for subareolar breast cancers is a satisfying treatment modality in terms of both cosmetic results and survival rates.

Adult↗

Thin section computed tomography in the prone position for detection of axillary lymph node metastases in breast cancer.

Presence or absence of lymph node metastases is the most accurate prognostic indicator in breast cancer. Clinical examination is unreliable in detecting involved nodes. Formerly, CT (computed tomography) was concluded to be an unreliable predictor of axillary lymph node involvement, primarily because of its low negative predictive value. In our institute, thin section CT (TS-CT) in the prone position was performed in patients with breast cancer to improve the predictability of axillary lymph node involvement. Pre-operative TS-CT examination of the axilla and breast was performed in 71 women with breast cancer. The sensitivity for involved nodes was 93.8%, the specificity 82.1%, and the accuracy 87. 3%. Based on these results, we concluded that TS-CT is an accurate predictor of axillary lymph node involvement. However, the upper limit of accuracy was approximately 85% for the imaging diagnoses, mainly because of the existance of micrometastases.

Adult↗

Analysis of radiation pneumonitis and radiation-induced lung fibrosis in breast cancer patients after breast conservation treatment.

We examined radiation pneumonitis in breast cancer patients after breast conservation treatment (BCT) and analysed the degree of radiation-induced lung fibrosis by computed tomographies of the chest (chest CT). Fifty-two breast cancer patients were treated with BCT, including breast irradiation and chemotherapy. These patients symptomatic of radiation pneumonitis were examined every two to four weeks. Chest X-rays and chest CT were performed about one year after irradiation. symptoms due to radiation pneumonitis was registered in 9.6% of patients. lungs showed fibrotic changes by chest CT in 90% of the cases. Concurrent or alternative chemotherapy increased the incidence of symptomatic radiation pneumonitis and, to a certain extent, the degree of fibrotic change in the lung after BCT.

Adult↗

The effects of nicotinamide plus carbogen or pions for microscopic SCCVII tumors.

We evaluated the sensitizing effect of nicotinamide plus carbogen (N&C) and the relative biological effectiveness (RBE) of pions on microscopic tumors where necrotic tumor centers have not yet been established. Female C3H/He mice and SCCVII tumors were used. The irradiation started two days after tumor implantation. In experiment 1, the tumor beds were irradiated at various doses with 250 KVp photons in 5 fractions over 5 days. Nicotinamide (500 mg/kg/mouse/day in 0.2 ml) was injected intraperitoneally (i.p.) 60 min before irradiation, and carbogen (95% O2 + 5% CO2) was flushed at the rate of 10 l/min for 10 min before irradiation and throughout the entire irradiation procedure. In experiment 2, the tumor beds were irradiated at various doses with pions or 250 KVp photons in 10 fractions over 5 days. In both experiments, the mice were observed for 100 days. The rate of tumor appearance was evaluated and the 50% tumor control dose (TCD50) calculated. The sensitizing ratio (SR) of N&C obtained from the TCD50 assay was 1.46 and the RBE of pions was 1.24. The SR of N&C and the RBE of pions were lower for microscopic tumors than those previously reported for macroscopic tumors. These results were probably due to the absence or reduced presence of radiobiological hypoxic component in the microscopic lesion. However, N&C can be considered to provide an advantage for treatment of even clinical microscopic tumors.

Animals↗

Changes in the findings of dynamic MRI by preoperative CAF chemotherapy for patients with breast cancer of stage II and III: pathologic correlation.

Preoperative neoadjuvant chemotherapy is essential for treatment of patients with breast cancer who have a large tumor mass and/or regional lymph node involvement, in terms of both tumor shrinkage and further improvement of the survival rate. In order to safely perform breast-conservation treatment for these patients, a detailed diagnostic procedure for precisely evaluating the therapeutic response is needed. Dynamic magnetic resonance imaging (MRI) is thought to be important in the evaluation of responses to neoadjuvant therapy in patients with considerably large tumors, however, few studies have detailed the changes, as depicted by dynamic MRI, that can be expected with neo-adjuvant chemotherapy. The purpose of this study was to document the changes that occur in response to neoadjuvant chemotherapy and to correlate them with the pathological findings observed in the surgical specimen. The study was performed at Kochi Medical School Hospital from 1995 to 1998. The series consisted of 31 patients with stage II and III breast cancer. Prior to and after 1-5 courses of neoadjuvant chemotherapy, dynamic MRI examinations were performed. Eight of the time-intensity curves for the 10 grade 1a tumors flattened during neoadjuvant chemotherapy, while two remained the same. Six of the curves flattened for the 14 grade 1b tumors, 7 remained the same, and one spiked. And for the seven grade 2 tumors, two of the curves flattened and five remained the same (p=0.0340). In the five grade 1 tumors, the mean after/before normalized peak signal intensity ratio was 0.42+/-0.22. In the 18 grade 2 and 8 grade 3 tumors, the mean normalized signal intensity ratios were 0.59+/-0.28, 0.88+/-0.10, respectively (p<0.05). In the 15 tumors that showed shrinkage of the linear enhancement during neo-adjuvant chemotherapy, 10 had no remarkable intraductal spreading and 9 had a negative surgical margin. In the 16 tumors that had no shrinkage of the linear enhancement during chemotherapy, 13 had remarkable intraductal spreading and 12 had a positive surgical margin (p<0.05). It is concluded that dynamic MRI is a valuable tool for determining tumor response and predicting a positive surgical margin. Breast-conservation treatment can be performed for these patients by meticulous assessment using such detailed diagnostic procedures after local tumor control by combined chemotherapy with high dose-intensity.

Adult↗