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Biomedical subjects

T Inada

Publications and source records attributed to T Inada.

336 records · Page 19Linked to original sources

Time resolved properties of acoustic pulses generated in water and in soft tissue by pulsed proton beam irradiation--a possibility of doses distribution monitoring in proton radiation therapy.

Time-resolved acoustic pulses generated in water and in soft tissue by pulsed proton beam irradiation were observed. The spatial resolution of depth dose distribution in the clinically applied beam intensity is estimated about 3 mm by means of TOF measurement. The dependence of the acoustic signal intensity on the temperature of medium was examined. Proportionality of acoustic pulse intensity to absorbed dose per pulse was confirmed as well. These results suggest the possibility of clinical application to monitor dose distribution in the patient's body during irradiation of pulsed proton beam.

Humans↗

Multiple gastric carcinoid tumors with type A gastritis concomitant with gastric cancer: a case report.

We describe a case with multiple gastric carcinoid tumors combined with early gastric carcinoma originated from the type A gastritis-affected tissue. Microcarcinoid foci were observed from the deeper layers of the propria mucosa to the submucosa and were surrounded by endocrine cell micronests (ECMs), while carcinoma was limited within the mucosa. Serum gastrin level was high (1,100 pg/ml) pre-operatively but returned to normal (44 pg/ml) post-operatively. It suggested that the longstanding hypergastrinemia may have played a causative role in the development of multiple carcinoids and cancer. Surgical treatment was considered essential for treatment in this case of coincident multiple carcinoid tumors and cancer.

Adenocarcinoma↗

Thymidine phosphorylase expression in gastric cancer in association with proliferative activity and angiogenesis.

BACKGROUND: Thymidine phosphorylase (dThdPase) has been reported to stimulate angiogenesis in vivo. We investigated dThdPase expression in gastric cancer in association with angiogenesis and proliferative activity. MATERIALS AND METHODS: One hundred and forty-eight gastric cancer patients who had received radical gastrectomy were investigated. RESULTS: Positive dThdPase staining was observed in 98 cases. The microvessel counts for positive and negative cases were 44.1 and 29.6, respectively, representing a significant correlation. The mean PCNA index of positive cases was significantly higher than that of negative cases. The patients with positive dThdPase staining in high intensity displayed decreased post-operative survival compared to those without. CONCLUSION: Our results suggest that proliferative activity of gastric cancer is related to dThdPase expression and angiogenesis and that dThdPase expression is associated with angiogenesis. dThdPase expression could also be a prognostic factor for gastric cancer patients.

Adenocarcinoma↗

5-fluorouracil sensitivity and dihydropyrimidine dehydrogenase activity in advanced gastric cancer.

BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme of 5-fluorouracil (5-FU) catabolism. Several studies have demonstrated the clinical importance of DPD in cancer patients, suggesting that the efficacy of 5-FU may be related to DPD activity in tumor tissue. In the present study, DPD activity and chemosensitivity to 5-FU were evaluated in advanced gastric cancer. MATERIALS AND METHODS: Thirty-four gastric cancers from 32 patients were studied and chemosensitivity to 5-FU was evaluated by histoculture drug response assay. RESULTS AND CONCLUSION: DPD activity and tumor inhibition of 5-FU among all cases showed no significant correlation, but among 14 histologically differentiated cases significant correlation was observed. DPD activity may be useful in determining the 5-FU sensitivity of differentiated gastric cancer.

Antimetabolites, Antineoplastic↗

p53, bcl-2 and thymidine phosphorylase as predictive markers of chemotherapy in patients with advanced and recurrent gastric cancer.

PURPOSE: To study the relationship between expression of p53, bcl-2, thymidine phosphorylase and Ki-67 and the response to chemotherapy and survival in patients with recurrent and advanced gastric cancer. MATERIALS AND METHODS: Protein expression was assessed immunohistochemically in 28 patients treated with 5-fluorouracil, pirarubicin and cisplatin (FAP). RESULTS: The response rate in patients positive for p53 expression was 23% compared with 47% of p53-negative patients. The response rate was also reduced from 44% in patients negative for bcl-2 protein expression to 25% in bcl-2 positive patients. Thymidine phosphorylase (dThdPase) expression was observed in 20 patients (71%), 50% of whom responded to chemotherapy, while patients negative for dThdPase expression did not respond to chemotherapy. The correlation between response rate and dThdPase-positivity was statistically significant (p < 0.05). However, with regard to patient survival, p53- and bcl-2-negative patients showed significantly better survival than patients positive for p53 and/or bcl-2 (p = 0.036). CONCLUSION: While dThdPase expression may be a useful predictor of response to chemotherapies that include 5-FU, p53 and bcl-2 expression may predict the outcome of patients with recurrent and advanced gastric cancer following chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

Acute skin reactions observed in fractionated proton irradiation.

Between May 1985 and July 1987, 49 skin reactions of 43 patients treated by proton irradiation were observed at the Particle Radiation Medical Science Center (PARMS), The University of Tsukuba. Taking the peak skin score as an endpoint, the radiobiological effects [relative biological effectiveness (RBE) and time-dose relationships] of the proton beam in multi-fractionated treatments were estimated. Factors influencing the skin dose, such as the prescribed tumor dose, tumor site, and number of applied fields, were also analyzed. The following conclusions regarding acute skin reactions to the clinical use of proton irradiation were obtained: 1) the physical skin-sparing effect of proton irradiation in single-field irradiation, especially in superficial regions, is not large compared with that of high-energy photon irradiation; 2) multidirectional proton irradiation significantly reduced the skin dose and severity of acute reactions; 3) the radiobiological effects of the proton beam, RBE and the time factor, estimated in human skin in multi-fractional treatment were slightly smaller than those of X-rays, i.e., 0.92 and -0.25 +/- 0.09, respectively.

Dose-Response Relationship, Radiation↗

Human tumors are methionine dependent in vivo.

Methionine-dependence is a tumor-specific biochemical defect expressed by the inability or decreased ability of tumors to grow under the condition of methionine-depletion. Many reports have shown that methionine-dependence occurs in human tumors of all types, including fresh surgical specimens in vitro. However, in vivo determinations of methionine-dependence have thus far been made only in rodent malignant tumors using methionine-deficient diets. We report here for the first time that human cancer xenografts in nude mice are methionine-dependent and when fed a methionine-free diet tumor growth is greatly inhibited. The body weight of mice on the methionine-free diet was found to be maintainable by once-per-week administration of methionine. The data presented here suggest that methionine-dependence can be an important target for human cancer treatment.

Animals↗

Significance of para-aortic lymph node dissection in patients with advanced and recurrent gastric cancer.

Among 243 patients who underwent radical gastrectomy for advanced gastric cancer, 19 patients underwent radical gastrectomy with extended lymphadenectomy including cancer-positive para-aortic lymph nodes. Their prognosis was unexpectedly good, with a mean postoperative survival time of 24.1 months and a 2-year-survival rate of 42.4 percent. Another 4 patients developed para-aortic lymph node recurrence detected by computed tomographic scan during a follow-up examination. These 4 patients were treated with macroscopic curative dissection of the para-aortic lymph nodes. Although 2 of the 4 patients died within 6 months after re-operation, the prognosis of the other two patients was rather good when treated with active combination chemotherapy consisting of 5-fluorouracil, adriamycin and cisplatin. Dissection of para-aortic lymph nodes is considered of valuable in the treatment of advanced gastric cancer, and dissection of the para-aortic lymph node recurrence may also be valid when combined with potent chemotherapy.

Adult↗

5-FU-induced apoptosis correlates with efficacy against human gastric and colon cancer xenografts in nude mice.

Apoptosis may be an important mechanism by which cancer cells are killed by certain agents. It is reported here that apoptosis is a key event in the killing of human tumor cells by 5-fluorouracil (5-FU) in vivo. Apoptosis induced by 5-FU was determined using two human gastrointestinal tumor xenografts serially transplanted into nude mice: a gastric carcinoma (SC-1-NU) highly sensitive to 5-FU and a colon carcinoma (Co-4) less sensitive to 5-FU. Apoptosis was assayed using the terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-biotin nick end labeling method in paraffin-embedded tissue sections, and by flow-cytometric analysis. Apoptosis-positive cells increased gradually during treatment. 24 hours after the initiation of 5-FU treatment a maximum, of 15.4% of the Co-4 cells were apoptotic. 48 hours after the initiation of 5-FU treatment, apoptosis was found in 34% of the tumor cells in the SC-1-NU strain. Flow-cytometry demonstrated the increase of S-phase fractions in both strains after the administration of 5-FU, and this coincided with the appearance of apoptotic-positive cells. Although the intrinsic. TS activities of two strains differed, TS activities were markedly suppressed in both strains immediately after the administration of 5-FU. Concentration of 5-FU in RNA (F-RNA) increased gradually in both strains, reaching a maximum 24 hours after the administration of 5-FU. These results suggest that apoptosis and inhibition of DNA synthesis induced by 5-FU are closely associated with its antitumor effect.

Animals↗

Methionine-depletion modulates the efficacy of 5-fluorouracil in human gastric cancer in nude mice.

Human tumors are generally methionine (MET)-dependent in that their growth is inhibited by MET-depletion down to levels that will still allow normal cell growth. The differential effect of methionine depletion on tumor and normal cells has suggested that methionine depletion may be able to modulate many and possibly all classes of cancer drugs. In this report, we determined if MET-depletion could modulate 5-fluorouracil (5-FU) efficacy on the human gastric cancer xenograft, SC-1-NU in nude mice. The tumor-bearing mice were treated with a MET-free diet and intraperitoneal administration of 5-FU at a dose of 30 mg/kg given for four cycles. MET depletion enhanced the antitumor activity of 5-FU by approximately two-fold with statistical significance of p < 0.05. The MET-free diet increased intratumoral thymidylate synthetase inhibition early after 5-FU administration; Therefore, MET-depletion was thought to increase the 5-FU antitumor activity by modulating intratumoral folate metabolism. The data in this report suggest the high clinical potential of methionine depletion, combined with 5-FU and leucovorin on refractory tumors such as stomach cancer.

Animals↗

Bcl-2 expression as a prognostic factor of survival of gastric carcinoma.

BACKGROUND: Although the bcl-2 proto-oncogene is important in determining tumor cell susceptibility to apoptosis, no data about the clinical importance in gastric cancer are available. METHODS: We analyzed bcl-2 and p53 expression, proliferative activity, and tumor apoptosis in locally advanced gastric carcinomas from 84 patients. RESULTS: Immunohistochemical analysis indicated that 41.7% and 48.8% of the tumors were bcl-2-positive, respectively. The apoptotic fraction was significantly lower in bcl-2-positive than negative tumors. Univariate analysis indicated low apoptotic fraction was one of the poor prognostic factors. Multivariate analysis showed a trend toward improved survival in bcl-2-positive patients. In patients with lymph node metastases more severe than group 2 lymph node, survival was significantly longer in those with bcl-2-positive tumors. CONCLUSIONS: The expression of bcl-2 and the high apoptotic fraction were concluded to be important prognostic factors of survival in patients with advanced gastric cancer.

Adenocarcinoma↗