Eiko Nakata

Results of radiation therapy combined with nedaplatin (cis-diammine-glycoplatinum) and 5-Fluorouracil for postoperative locoregional recurrent esophageal cancer

BackgroundAlthough the effectiveness of radiotherapy with concurrent administration of several anti-tumor drugs for postoperative recurrent esophageal cancer has been demonstrated, the results are not satisfactory. The purpose of the present study was to evaluate the effectiveness and safety of radiotherapy combined with nedaplatin and 5-FU for postoperative locoregional (excluding hematogenous metastasis) recurrent esophageal cancer.MethodsIn June 2000, we started a phase II study on treatment of postoperative locoregional recurrent esophageal cancer with radiotherapy (60 Gy/30 fr/6 weeks) combined with chemotherapy consisting of two cycles of nedaplatin (70 mg/m2/2 h) and 5-FU (500 mg/m2/24 h for 5 days).The primary endpoint of the present study was overall survival rate, and the second endpoints were irradiated-field control rate, tumor response and toxicity.ResultsA total of 30 patients were included in this study. The 1-year and 3-year overall survival rates were 60.6% and 56.3%, respectively, with a median survival period of 39.0 months, and the 1-year and 3-year irradiated-field control rates were 86.4% and 72%, respectively. Complete response and partial response were observed in 13.3% and 60.0% of the patients, respectively. Grade 3 or higher leukocytopenia and thrombocytopenia were observed in 30% and 3.3% of the patients, respectively, but renal toxicity of grade 3 or higher was not observed. The regimen was completed in 76.7% of the patients.In univariate analysis, the difference between survival rate in preradiotherapy performance status, recurrent pattern (worse for patients with anastomotic recurrence) and age (worse for younger patients) were statistically significant.ConclusionRadiotherapy combined with nedaplatin and 5-FU is a safe and effective salvage treatment for postoperative locoregional recurrent esophageal cancer.

A diarylpentanoid curcumin analog exhibits improved radioprotective potential in the intestinal mucosa

Abstract Purpose: To best enhance the effects of radiotherapy, it is important to minimize adverse events, including free radical-induced intestinal cell damage. Given the threat of nuclear power plant accidents or nuclear terrorism, there is an urgent need for radioprotectants to counteract the radiation-induced toxicity and/or injuries. Curcumin exhibits protective effects against gamma irradiation; however, its in vivo efficacy is decreased due to the low bioavailability. We examined the radioprotective effect of a newly synthesized curcumin analog, GO-Y031, on 11-Gy X-ray-induced intestinal mucosal damage in mice. Materials and methods: The radioprotection experiments were conducted by using C57BL/6J or Jcl:ICR mice. Molecules related to radiation damage, including p53, Bax, Bcl-2, cleaved caspase-3, and reactive carbonyl species (RCS), were investigated immunohistochemically. Results: GO-Y031 protected against crypt hypoplasia relative to a mock treatment at 0.5% (weight/weight); the number of crypts were 11.00 ± 2.00/circumference (mm) in treated versus 6.86 ± 0.99/mm in mock-treated C57BL/6 mice (p = 0.0079). GO-Y031 also reduced the levels of RCS, p53, and cleaved caspase-3 accumulation in the irradiated intestinal cells. Conclusions: GO-Y031 suppresses the accumulation of RCS and apoptosis-related molecules in irradiated cells. This compound may be a good primary radioprotective compound.

Current abstracts of the articles published in The Japanese Journal of Nuclear Medicine

Sympathetic nerve system is activated as a compensatory mechanism in heart failure. However, excessive activation of sympathetic nerve system deteriorates disease state. Sympathetic nerve system can be suppressed with N-type Ca 2+ channel blocker. An antihypertensive drug, cilnidipine, is a dual L/N-type Ca 2+ channel blocker. We studies usefulness of cilnidipine in treating with chronic heart failure with 123I-MIBG myocardial scintigraphy. We enrolled 24 patients with stable chronic heart failure. Twelve patients were treated with ACE-inhibitors, diuretics and cardiotonics (control group), and the other 12 patients were treated with ACE-inhibitors, diuretics, cardiotonics and cilnidipine (cilnidipine group). We examined blood pressure, heart rate, norepinephrine level, brain natriuretic peptide (BNP) level, cardiothoracic ratio on chest X-ray, ejection fraction of left ventricle on two-dimensional echocardiography, count rate of heart to mediastinum (H/M) and washout rate (WOR) on 123I-MIBG myocardial scintigraphy before and six months after medication. Symptom was improved in 8 patients in the control group and 10 patients in the cilnidipine group after medication. And another parameters were also improved in the both groups after medication. However the degree of change in blood pressure (mmHg) was 21.2 _+ 8.0 in the cilnidipine group and 10.8 _+ 9.1 in the control group, that in heart rate (/min) was 24.1 +_ 6.8 and 16.2 _ 11.0, that in BNP level (pg/m/) was 65.2 _ 12.0 and 42.8 _ 11.1, that in H/M was 0.30 _ 0.08 and 0.19 _+ 0.09, that in WOR was 19.4 _ 5.6 and 12.2 _ 7.0, respectively. And the degree of these changes were larger in the cilnidipine group (p < 0.05). These findings suggested that cilnidipine, a dual L/N-type Ca 2+ channel blocker, might be useful in treating with chronic heart failure.