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Takashi Ogino

Publications and source records attributed to Takashi Ogino.

36 records · Page 2Linked to original sources

Chronic allergy to dietary ovalbumin induces lymphocyte migration to rat small intestinal mucosa that is inhibited by MAdCAM-1.

Few models have described a chronic food allergy with morphological changes in the intestinal mucosa. Here we established an ovalbumin (OVA)-induced, cell-mediated, allergic rat model and examined lymphocyte migration in the gut. Brown Norway rats were intraperitoneally sensitized to OVA and then given 10 mg OVA/day by gastric intubation for 6 wk. Lymphocyte subsets and adhesion molecules were examined immunohistochemically, and the migration of T lymphocytes to microvessels of Peyer's patches and villus mucosa was observed by using an intravital microscope. Serum OVA-specific IgG and IgE levels were increased in animals repeatedly exposed to OVA. Significant villus atrophy and increased crypt depth was accompanied by increased infiltration of T lymphocytes in the small intestinal mucosa of the group given OVA. Expression of rat mast cell protease II and of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) was also increased in these groups. The administration of anti-MAdCAM-1 antibody significantly attenuated the OVA-induced changes in the mucosal architecture and in CD4 T lymphocyte infiltration. Intravital observation demonstrated that in rats with a chronic allergy, T lymphocytes significantly accumulated in villus microvessels as well as in Peyer's patches via a MAdCAM-1-dependent process. Our model of chronic food allergy revealed that lymphocyte migration was increased with MAdCAM-1 upregulation.

Animals↗

Nonrandomized comparison between definitive chemoradiotherapy and radical surgery in patients with T(2-3)N(any) M(0) squamous cell carcinoma of the esophagus.

PURPOSE: To compare the treatment results between radical surgery and definitive chemoradiotherapy for resectable squamous cell carcinoma of the esophagus and to identify useful clinicopathologic and biologic markers to select better treatment. METHODS AND MATERIALS: Between August 1992 and April 1999, 98 consecutive patients were selected for this study; 53 were treated with chemoradiotherapy and 45 with surgery. The patients in the chemoradiotherapy group received 5-fluorouracil combined with cisplatin plus 60 Gy of radiation, and those in the surgery group received an esophagectomy with radical node dissection. Biologic markers were investigated immunohistochemically using pretreatment biopsy specimens. RESULTS: The baseline clinical TNM stage was more advanced in the chemoradiotherapy group than in the surgery group. With a median follow-up period of 43 months, the 5-year survival rate was 46% in the chemoradiotherapy and 51% in the surgery group, without statistical significance (p = 0.47, log-rank test). Cox regression analysis for prognosis revealed that epidermal growth factor receptor positivity, high microvessel density, and cyclin D1 positivity yielded a low value for relative risk (0.66, 0.54, and 0.62, respectively), which favored chemoradiotherapy over surgery, without statistical significance. CONCLUSION: This nonrandomized study showed a trend for the chemoradiotherapy in the treatment of esophageal carcinoma, but the results need to be confirmed by additional study.

Adult↗

Long-term toxicity after definitive chemoradiotherapy for squamous cell carcinoma of the thoracic esophagus.

PURPOSE: To assess the long-term toxicity after definitive chemoradiotherapy (CRT) for squamous cell carcinoma (SCC) of the esophagus. PATIENTS AND METHODS: Patients newly diagnosed with SCC of the esophagus and treated with definitive CRT between 1992 and 1999 in our institution were recruited from our database on the basis of the following criteria: age </= 75 years, performance status (PS; based on the Eastern Cooperative Oncology Group scale) 0 to 2, and clinical tumor-node-metastasis system stage I to IVA. The CRT consisted of two cycles of cisplatin 40 mg/m2 on days 1 and 8, and continuous infusion of fluorouracil 400 mg/m2/d on days 1 to 5 and 8 to 12, repeated every 5 weeks with concurrent radiotherapy of 60 Gy in 30 fractions. For the assessment of toxicity, the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme was adopted. RESULTS: A total of 139 patients were recruited, and their characteristics were as follows: median age, 62 years (range, 38 to 75 years); 121 males and 18 females; 96 patients PS 0, 42 patients PS 1, and one patient PS 2; 15 patients T1, 11 patients T2, 60 patients T3, and 53 patients T4; and 101 patients M0, 38 patients M1a. With a median follow-up of 53 months, the median survival time and 5-year survival rate were 21 months and 29%, respectively. Of 78 patients with complete remission, two patients died as a result of acute myocardial infarction. Grade 2, 3, and 4 late toxicities occurred with the following incidences: pericarditis in eight patients, seven patients, and one patient, respectively; heart failure in zero, zero, and two patients; pleural effusion in seven, eight, and zero patients; and radiation pneumonitis in one patient, three patients, and zero patients, respectively. CONCLUSION: Definitive CRT for SCC of the esophagus is effective with substantial toxicities. Additional investigation to minimize the normal tissue toxicities is warranted.

Adult↗

Exposure to fatty acids modulates interferon production by intraepithelial lymphocytes.

Intraepithelial lymphocytes (IELs) play important roles in intestinal mucosal immunity. Although fatty acids are known to modulate the functions of immune effector cells, there has been no information about how fat exposure affects immunological function of IELs. In this study, we examined how fatty acids of various chain lengths modulate the production of interferon (IFN)-gamma by IELs stimulated with T-cell receptor (TCR) or interleukin (IL)-12/IL-18. IELs isolated from the small intestine of BALB/c mice were stimulated with plate-coated anti-CD3 monoclonal antibody (mAb) or IL-12/IL-18. They were coincubated in microtiter plates for 3 days with various concentrations of fatty acid micelles. We used arachidonic acid, linoleic acid, and oleic acid as long-chain fatty acids, and used octanoic acid as a medium-chain fatty acid. IFN-gamma in the supernatants were measured by ELISA, and the expression of IFN-gamma mRNA in IELs was determined by RT-PCR. Significant production of IFN-gamma from IELs was observed after anti-CD3 mAb stimulation. The combination of IL-12 and IL-18 induced significant levels of IFN-gamma production without TCR stimulation. Increased IFN-gamma mRNA was also observed after anti-CD3 or IL-12/IL-18 stimulation. Long-chain fatty acids dose-dependently inhibited the stimulated-IFN-gamma production at concentrations greater than 10 micro M, but the medium-chain fatty acid did not cause any significant changes in IFN-gamma production. IFN-gamma production from gammadelta IELs was very low compared with alphabeta IELs, however, both populations showed similar attenuating patterns when treated with long-chain fatty acids. There is a possibility that the exposure of IELs to intraluminal fatty acids significantly modifies the immune function of intestinal mucosa.

Animals↗

Intraoperative and conformal external-beam radiation therapy with protracted 5-fluorouracil infusion in patients with locally advanced pancreatic carcinoma.

BACKGROUND: Chemoradiotherapy is widely used for patients with locally advanced pancreatic carcinoma. The purpose of this study was to clarify the efficacy and feasibility of chemoradiotherapy with more intensive radiotherapy in these patients, using a combination of intraoperative radiotherapy (IORT), conformal external-beam radiaotherapy (EBRT), and protracted 5-fluorouracil (5-FU). METHODS: Thirty patients with unresectable locally advanced pancreatic carcinoma were enrolled in this Phase II study. The treatment consisted of IORT (25 grays [Gy]), followed by EBRT (40 Gy in 20 fractions, 5 times per week), and concurrent protracted 5-FU infusion (200 mg/m(2)), beginning 2-4 weeks after IORT. The authors evaluated the efficacy and adverse effects of this treatment by following up patients for 12.0-28.1 months. Survival from the date of IORT was calculated using the Kaplan-Meier method. RESULTS: In 11 of the 30 patients, metastatic spread was detected in the abdominal cavity at laparotomy. The full EBRT dose was administered in 28 of the 30 patients. Of the remaining 2 patients, EBRT was terminated at 8 Gy due to progression of brain metastasis and another patient did not receive EBRT or chemotherapy due to massive ascites after IORT. The overall response rate for primary pancreatic tumor on dynamic computed tomography scan was 23.3% (7 partial responses). Grade 3 or 4 toxicity (according to the National Cancer Institute Common Toxicity Criteria) was observed in 15 of the 28 patients who received the full irradiation dose (53.6%). These included anorexia, nausea, emesis, fatigue, leukopenia, and/or elevation of transaminase levels. There were no directly treatment-related deaths, but 1 patient died of hepatic failure related to late effects of irradiation after 25.6 months. The median survival time of the 30 patients was 7.8 months and the 2-year survival rate was 8.1%. The median survival time of the 19 patients without metastatic spread in the abdominal cavity was 12.9 months and that of the 11 patients with metastatic spread was 5.8 months. CONCLUSIONS: The present regimen of chemoradiotherapy is not superior to conventional chemoradiotherapy (EBRT and 5-FU) for patients with locally advanced pancreatic carcinoma.

Adenocarcinoma↗

Efficacy of chemoradiotherapy on pain relief in patients with intrapelvic recurrence of rectal cancer.

PURPOSE: To assess the efficacy of chemoradiotherapy on pain relief in patients with intrapelvic recurrence of rectal cancer. METHODS: The records of 30 patients treated with radiotherapy with or without chemotherapy for intrapelvic recurrence of rectal cancer between September 1993 and February 1999 were retrospectively reviewed. There were 17 patients in the chemoradiotherapy (CRT) group and 13 patients in the radiotherapy alone (RTA) group. Simultaneous extrapelvic distant metastases were found in 11 patients in the CRT group and in seven patients in the RTA group. Radiotherapy was administered with a median total dose of 50 Gy in both groups. In the CRT group, 15 patients received 5-fluorouracil by continuous infusion and two patients received irinotecan in a biweekly infusion schedule during the course of radiotherapy. The response rate and duration of pain relief were evaluated and were compared between the two groups. RESULTS: The response rate of pain relief in the CRT and RTA was 100 and 77%, respectively. The median duration of pain relief in the CRT and RTA groups was 7.8 and 4.0 months, respectively and there was a significant difference between the two groups (P = 0.019). The median survival time from the start of radiotherapy was 15.1 and 9.3 months in the CRT and RTA groups, respectively, and there was a significant difference between the two groups (P = 0.046). CONCLUSIONS: The results suggest that chemoradiotherapy for intrapelvic recurrence of rectal cancer for the purpose of pain relief appears to be more effective than radiotherapy alone.

Adenocarcinoma↗

[Heavy charged particle radiotherapy--proton beam].

Proton beam therapy (PBT) makes it possible to deliver a higher concentration of radiation to the tumor by its Bragg-peak, and is easy to utilize due to its identical biological characteristics with X-rays. PBT has a half-century history, and more than 35,000 patients have been reported as having had treatments with proton beams worldwide. The historic change to this therapy occurred in the 1990s, when the Loma Linda University Medical Center began clinical activity as the first hospital in the world to utilize a medically dedicated proton therapy facility. Since then, similar hospital-based medically dedicated facilities have been constructed. Results from around the world have shown the therapeutic superiority of PBT over alternative treatment options for ocular melanoma, skull base sarcoma, head and neck cancer, lung cancer, esophageal cancer, hepatocellular carcinoma, and prostate cancer. PBT is expected to achieve further advancement both clinically and technologically.

Cancer Care Facilities↗

Water permeability of capillaries in the subfornical organ of rats determined by Gd-DTPA(2-) enhanced 1H magnetic resonance imaging.

The water permeability of capillaries in the subfornical organ (SFO) of rat was measured by a (1)H nuclear magnetic resonance method in combination with a venous injection of a relaxation reagent, gadolinium-diethylene triamine-N,N,N',N",N"-pentaacetic acid (Gd-DTPA(2-)), which could not pass through the blood-brain barrier (BBB). Judging from results of Gd-DTPA(2-) dose dependency in the intact brain and the BBB-permeabilized brain, Gd-DTPA(2-) could not have leaked out from the capillaries in the cortex, thalamus or SFO, but it could have been extravasated in the posterior lobe of the pituitary gland. The longitudinal (T(1)) relaxation time of water in the SFO region was measured by inversion-recovery magnetic resonance imaging at 4.7 T. The T(1) relaxation rates (1/T(1)) before and after Gd-DTPA(2-) infusion were 0.70 +/- 0.02 s(-1) (mean +/- S.E.M., n = 9) and 1.53 +/- 0.11 s(-1) (n = 9), respectively. The rate constant for water influx to the capillaries was estimated to be 0.84 +/- 0.11 s(-1) (n = 9) which corresponds with a diffusive membrane permeability (P(d)) of 3.7 x 10(-3) cm s(-1). Compared with values found in the literature available on this subject, this P(d) value for the capillaries in the SFO was the same order of magnitude as that for transmembrane permeability of water for the vasa recta, and it may be 10-100 times larger than that of the blood-brain barrier in the cortex. Areas of the cortex and thalamus showed minimal changes in the T(1) relaxation rate (ca 0.09 s(-1)), but these values were not statistically significant and they corresponded to P(d) values much smaller than those found in the SFO. From these results, we conclude that the capillaries in the SFO have one of the highest water permeability values among all of the capillaries in the brain. It is also suggested that this magnetic resonance imaging, based on T(1) relaxation rate, is a useful method to detect local water permeability in situ.

Animals↗

Quinoline-3-carbothioamides and related compounds as novel immunomodulating agents.

A series of quinoline-3-carbothioamides and their analogues was prepared via four synthetic routes and evaluated for their antinephritic and immunomodulating activities. The optimal compound 9g strongly inhibited the T-cell independent antibody production in mice immunized with TNP-LPS and was highly effective in two nephritis models, namely chronic graft-versus-host disease and autoimmune MRL/l mice.

Adjuvants, Immunologic↗

Detection of hypothalamic activation by manganese ion contrasted T(1)-weighted magnetic resonance imaging in rats.

To examine the usefulness of Mn(2+) contrasted magnetic resonance imaging (MRI) in hypothalamic imaging, images obtained using T(1)-weighted MRI were compared with Fos expression, which is known to increase after activation of voltage-dependent Ca(2+) channels. Intravenous infusion of MnCl(2) elicited a rapid increase in the T(1)-weighted MRI signal intensity in the vessels and ventricles, but not in the brain parenchyma, suggesting that Mn(2+) did not diffuse freely across the blood-brain barrier. When the blood-brain barrier was broken by right intracarotid arterial injection of 25% D-mannitol, an increased signal intensity was seen in the right brain. Intracarotid arterial injection of hypertonic NaCl elicited rapid and striking increases in signal intensity in the paraventricular hypothalamic nucleus, supraoptic nucleus, and preoptic area, which are thought to be involved in central osmotic regulation. These observations were consistent with the Fos expression results. These results indicate that Mn(2+) contrasted MRI is a useful technique for investigating the autonomic center in the hypothalamus.

Animals↗

Spatial heterogeneity of TNF-alpha-induced T cell migration to colonic mucosa is mediated by MAdCAM-1 and VCAM-1.

Relatively little is known about how recirculation of lymphocytes through the inflamed intestinal mucosa is regulated. The aim of this study was to investigate the dynamic process of T lymphocyte-endothelial cell adhesion in TNF-alpha-challenged murine colonic mucosa by intravital microscopy. T lymphocytes from spleen (SPL) and intestinal lamina propria (LPL) were fluorescence labeled, and their adhesion to microvessels in the colonic mucosa was observed. In TNF-alpha (25 microg/kg)-stimulated colonic venules, an enhanced adhesion of SPL and LPL was demonstrated, with dominant recruitment of LPLs. The magnitude of the increased LPL adhesion was more significant in the colon than in the small intestine. These T lymphocyte interactions in the colonic mucosa were significantly reduced by blocking MAbs against either mucosal addressin cell adhesion molecule-1 (MAdCAM-1), VCAM-1, alpha(4)-integrin, or beta(7)-integrin but not by anti-ICAM-1. Immunohistochemistry revealed significant MAdCAM-1 expression in the lamina propria and VCAM-1 expression in the submucosa of TNF-alpha-treated colon. Spatial heterogeneity of MAdCAM-1 and VCAM-1 activation following TNF-alpha challenge may promote specific T lymphocyte recruitment in the inflamed colonic mucosa.

Animals↗

Phase II study of twice-daily high-dose thoracic radiotherapy alternating with cisplatin and vindesine for unresectable stage III non-small-cell lung cancer: Japan Clinical Oncology Group Study 9306.

PURPOSE: To evaluate the efficacy and toxicity of high-dose thoracic radiotherapy (TRT) alternating with chemotherapy (CH) for unresectable stage III non--small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Forty-one patients received TRT with 1.5 Gy twice daily, 5 days a week, on weeks 1, 2, 5, 6, and 9, up to a total dose of 66 to 72 Gy, alternating with cisplatin 80 mg/m(2) on day 1 and vindesine 3 mg/m(2) on days 1 and 8, repeated every 4 weeks, for two or three courses beginning on week 3. RESULTS: The median (range) total dose of TRT and number of CH courses were 72 Gy (16.5 to 72 Gy) and three (zero to three), respectively. Delay in TRT > or = 5 days was observed in 24 (75%) of 32 patients who completed the projected treatment, due to leukopenia in 12, esophagitis in seven, infection in two, and other causes in three patients. Partial responses were obtained in 36 patients (88%). The median survival time and 3- and 5-year survival rates were 18.4 months, 24%, and 10%, respectively. Grade 3 or 4 leukopenia and esophagitis developed in 32 and seven patients, respectively. Grade 3 or 4 late esophageal toxicity developed in two patients. CONCLUSION: Alternating high-dose TRT and CH for stage III NSCLC produced a high response rate with median and long-term survival comparable to prior trials utilizing standard approaches in this population. Acute and late esophageal toxicity was observed and interruption of TRT was required in most of the patients.

Antineoplastic Agents↗

Short-course palliative radiotherapy for airway stenosis in non-small cell lung cancer.

BACKGROUND: The majority of patients with non-small cell lung cancer have inoperable disease that is already too advanced for radical treatment at the initial diagnosis. But patients who suffer from symptoms caused by intrathoracic tumor often require palliative treatment to relieve the symptoms. We investigated, retrospectively, the outcome of short-course palliative radiotherapy for airway stenosis in non-small cell lung cancer. METHODS: Between October 1997 and June 2001, 24 patients were treated by palliative radiotherapy to relieve airway stenosis caused by intrathoracic tumor. The short-course radiotherapy consisted of a total dose of 30 Gy given in ten fractions over 2 weeks. The effect of treatment was assessed by improvement of radiographic findings. The duration of palliation and this duration as a percentage of the remaining survival time were also investigated. RESULTS: Palliation of airway stenosis was achieved in 13 (54.2%) patients. The time until palliation was achieved ranged from 11 to 44 days (median, 24 days). The duration of palliation ranged from 44 to 351 days (median, 116 days). In the palliated patients, the median survival time was 192 days, while that of the non-responders was 43 days. The duration of palliation as a percentage of the remaining lifetime ranged from 41% to 96% (median, 66%). CONCLUSIONS: Short-course palliative radiotherapy of 30 Gy in ten fractions over 2 weeks achieved good palliation without severe acute toxicities in over half of the patients. It is suggested that, in the palliated patient, the airway can be, potentially, maintained over the long term.

Adult↗

Radiotherapy after transcatheter arterial chemoembolization for patients with hepatocellular carcinoma and portal vein tumor thrombus.

Transcatheter arterial chemoembolization (TACE) is used in the treatment of hepatocellular carcinoma; however, it has limited effect on portal vein tumor thrombus (PVTT). The purpose of this study was to assess the feasibility and efficacy of radiotherapy targeting the PVTT after TACE for the tumor in the hepatic parenchyma. TACE was performed using epirubicin hydrochloride, iodized poppy seed oil, and gelatin sponge particles. Radiotherapy was performed targeting the PVTT to a total dose of 50 Gy in 25 fractions during 5 weeks. Twenty consecutive patients were treated with this combined treatment. Sixteen of 20 patients could complete the planned radiotherapy. Partial response was observed in 10, no change in 4, and progression in 6. The response rate was 50% (95% CI 28-72%). The 1-year overall survival rate was 25% (95% CI 6-44%), and the median survival time was 5.3 months. It was difficult to determine the late toxicities because of disease progression and additional TACE, and only one patient died without disease progression. Radiotherapy after TACE is feasible for patients with hepatocellular carcinoma and PVTT. The survival figure, however, is still dismal, and further investigation is needed to establish the best combination of treatment modalities.

Adult↗

A new nonpeptide tachykinin NK1 receptor antagonist isolated from the plants of Compositae.

To find new tachykinin NK1 receptor antagonists from natural sources, we examined the tachykinin antagonist activity in the extracts of approximately 200 species of plants by the use of isolated guinea pig ileum. As a result, we discovered a novel and potent NK1 receptor antagonist in the extract of dried flowers of Matricaria chamomilla L. (chamomile). The structure of the antagonist was established as N1,N5,N10,N14-tetrakis[3-(4-hydroxyphenyl)-2-propenoyl]-1,5,10,14-tetraazatetradecane (tetracoumaroyl spermine, 1a). The Ki values of 1a, estimated from the inhibitory action on the substance P (SP)-induced contraction of the guinea pig ileum and the inhibition of the binding of [3H][Sar9, Met(O2)11]SP to human NK1 receptors, were 21.9 nM and 3.3 nM, respectively. 1a is the first potent NK1 receptor antagonist from natural sources and it has a unique structure of a polyacylated spermine. 1a was concentrated in pollen of Matricaria chamomilla L. and was also found in the extracts of flowers of other four species of Compositae. In addition, we found N1,N5,N10-tris[3-(4-hydroxyphenyl)-2-propenoyl]-1,5,10,14-tetraazatetradecane (2) as a new compound in the extract of flowers of Matricaria chamomilla L., which did not exhibit any tachykinin antagonist activity. A number of related compounds were synthesized, and the structure-activity relationship was studied.

Alkenes↗

Hepatic arterial infusion of 5-fluorouracil and extrabeam radiotherapy for liver metastases from pancreatic carcinoma.

BACKGROUND/AIMS: To examine the efficacy and safety of a combined modality therapy consisting of hepatic arterial infusion of 5-fluorouracil and external-beam radiotherapy in patients with advanced pancreatic carcinoma. METHODOLOGY: Hepatic arterial infusion chemotherapy consisted of 5-FU 1000mg/m2 administrated as a 5-hr continuous infusion once weekly. External-beam radiotherapy (total dose, 50Gy; 2Gy/day) was delivered to the pancreas tumor concurrently for 5-6 weeks. Seventeen patients with no distant metastases except to the liver were enrolled in this study. RESULTS: Patients received a median of 13 cycles of chemotherapy. Sixteen of 17 patients received a total radiotherapy dose of 50Gy. In one patient, treatment was discontinued after 24Gy of radiotherapy and 2 cycles of chemotherapy because of progressive disease. Nausea and vomiting were the most common types of toxicity. Grade 3 or worse toxicity was observed in 2 patients. Four patients developed gastroduodenal ulcers. Of the 16 patients, 7 (41%) showed a partial response, and 9 (53%) showed no change. The median overall survival was 4.5 months and 1-yr overall survival of 11.8% was observed. CONCLUSIONS: The combined therapy is active and well tolerated, but results in a poorer prognosis, in spite of its high initial response rate.

Aged↗