BackgroundChemoradiation therapy (CRT) has been widely used for unresectable esophageal squamous cell carcinoma (ESCC) patients. However, many patients develop local recurrence after CRT. In this study, we hypothesized that the immunotherapy by peptide vaccine may be effective for the eradication of minimal residual cancer cells after CRT. This study was conducted as a phase I clinical trial of multiple-peptide vaccine therapy combined with CRT on patients with unresectable ESCC.Patients and methodsHLA-A*2402 positive 11 unresectable chemo-naïve ESCC patients were treated by HLA-A*2402-restricted multi-peptide vaccine combined with CRT. The peptide vaccine included the 5 peptides as follows; TTK protein kinase (TTK), up-regulated lung cancer 10 (URLC10), insulin-like growth factor–II mRNA binding protein 3 (KOC1), vascular endothelial growth factor receptor 1 (VEGFR1) and 2 (VEGFR2). CRT consisted of radiotherapy (60 Gy) with concurrent cisplatin (40 mg/m2) and 5-fluorouracil (400 mg/m2). Peptide vaccines mixed with incomplete Freund’s adjuvant were injected subcutaneously once a week on at least 8 occasions combined with CRT.ResultsVaccination with CRT therapy was well-tolerated, and no severe adverse effects were observed. In the case of grade 3 toxicities, leucopenia, neutropenia, anemia and thrombocutopenia occurred in 54.5%, 27.3%, 27.3% and 9.1% of patients, respectively. Grade 1 local skin reactions in the injection sites of vaccination were observed in 81.8% of patients. The expressions of HLA class I, URLC10, TTK, KOC1, VEGFR1 and VEGFR2 antigens were observed in the tumor tissues of all patients. All patients showed peptide-specific cytotoxic T lymphocytes responses in at least one of the 5 kinds of peptide antigens during the vaccination. Six cases of complete response (CR) and 5 cases of progressive disease (PD) were observed after the 8th vaccination. The 4 CR patients who continued the peptide vaccination experienced long consistent CR for 2.0, 2.9 4.5 and 4.6 years.ConclusionsA combination therapy of multi-peptide vaccine with CRT can successfully be performed with satisfactory levels of safety, and application of this combination therapy may be an effective treatment for patients with unresectable ESCC.Trial registrationClinicalTrial.gov, number NCT00632333.
Abstract. microRNAs (miRNAs) are small non-coding RNAs that regulate target gene expression. It is known that miRNA-107 (miR-107) promotes cancer invasion and metastasis. However, the relationship between clinicopathological factors and the prognostic significance of miR-107 for gastric cancer patients remains elusive. In this study, we evaluated the prognostic value of miR-107 using tissue samples from gastric cancer patients. Furthermore, the relationship between miR-107 and the mRNA levels of its target gene DICER1 was examined. The expression levels of miR-107 and DICER1 mRNA in tumor tissues and adjacent normal tissues of 161 gastric cancer patients were examined (TNM stage I, 29 patients; stage II, 31 patients; stage III, 51 patients and stage IV, 50 patients). miR-107 levels were measured by TaqMan microRNA assays, and DICER1 mRNA levels were measured by the TaqMan real-time RT-PCR method. In the analysis by real-time PCR-based miRNA arrays using pooled RNA samples from five gastric cancer patients, expression of miR-107, miR-21, miR-196a, miR-26b, miR-9, miR-142-3p, miR-30b, miR-150, miR-191 and miR-17 was found to be upregulation. The mean expression level of miR-107 was significantly higher in the tumor tissues compared to that of normal tissues. In the comparison of clinicopathological factors, miR-107 expression showed significant association with depth of tumor invasion, lymph node metastasis and stage. In Kaplan-Meier survival curve analysis, overall survival rates (OS) and disease-free survival rates (DFS) of patients with high miR-107 expression were significantly worse than those of patients with low miR-107 expression. In the Cox multivariate analysis, it was shown that miR-107 expression in gastric cancer tissues was an independent prognostic factor for OS and DFS. Significant inverse correlations were demonstrated between miR-107 and DICER1 mRNA. Our results indicate that miR-107 may be useful as an effective biomarker for prediction of a poor prognosis in gastric cancer patients.
The frequency and intensity of persistent chronic pain or discomfort after inguinal hernia repair was not high or severe. These data will be useful for further studies to determine the best treatment for adult inguinal hernia.
Pharmacists applied deprescribing, which is a process for the rational use of drugs, for 13 at-home patients. The standard used for the rational use of drugs was the``Guidelines for Medical Treatment and Its Safety in the Elderly'' (the Guidelines). The results of the deprescribing were discussed with physicians to determine prescriptions. After the prescription change, activities of daily living (ADL) and QOL were assessed using the Barthel Index and SF-36v2, respectively. Potentially inappropriate medications (PIMs) were detected in 10 of the 13 patients (76.9%). This detection rate is higher than previous PIM detection rates of 48.4% and 40.4% reported in prescriptions for home-care patients in Japan under the Beers and STOPP/START criteria. The Guidelines appeared useful as a decision support tool for deprescribing. The patients continuing the changed prescriptions showed no decrease in ADL or QOL after deprescribing, suggesting its rationality. The 10 measurement items of the Barthel Index were all suitable for evaluating the physical conditions of the patients. Meanwhile, SF-36v2 includes many items, but few indexes were directly applicable.Key words-deprescribing; potentially inappropriate medication; home-care patient; activities of daily living; QOL; criteria One agent less as physician prescribed a compounding drug. Vol. 137 No. 5 (2017) 628 628 YAKUGAKU ZASSHI Vol. 137 No. 5 (2017) 3. 薬剤師が作成した処方変更提案及び医師との YAKUGAKU ZASSHI 協議結果Step 1 において抽出された 13 薬剤の 中止と 1 薬剤の用量変更は,すべて受け入れられた.
Vagotomy has a major impact on the gut cytokine milieu. Vagotomy may initially inhibit both pro- and anti-inflammatory cytokine production, while both later increase.
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