We investigated the effectiveness of chemoradiotherapy for the treatment of lymph node recurrence and hematogenous metastasis after esophagectomy for esophageal squamous cell carcinoma. Between 2001 and 2006, 216 patients with thoracic esophageal squamous cell carcinoma had curative esophagectomy. Of those, 23 with lymph node recurrence received chemoradiotherapy (50.0-68.8 Gy). In addition, five patients had isolated recurrences in a distant organ and received chemoradiotherapy (50.0-60.0 Gy). We analyzed outcomes from the radiotherapy for recurrent esophageal cancer. The 1-, 2-, and 5-year survival rates after recurrence for the 23 patients whose lymph node recurrence was treated with chemoradiotherapy were 52, 31, and 24%, respectively, and the median survival time was 13 months. Among the five patients with recurrent tumors in a distant organ, chemoradiotherapy produced a complete response in two patients, a partial response in one patient, and stable disease in two patients, giving an effectiveness rate of 60% (complete response + partial response). Chemoradiotherapy has a beneficial prognostic effect in patients with lymph node recurrence of esophageal squamous cell carcinoma. Chemoradiotherapy for a metastatic tumor in a distant organ may be the treatment of choice in cases where systemic chemotherapy has proven ineffective.
Identification of reliable markers of radiosensitivity and the key molecules that donate susceptibility to anticancer treatments to esophageal cancer cells would be highly desirable. We found that the mRNA expression of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) was higher in radioresistant TE-5 and TE-9 cells than in radiosensitive TE-12 cloneA1 cells. Conversely, knocking down expression of IGF2BP3 mRNA in TE-5 and TE-9 cells using small interfering RNA significantly enhanced their radiosensitivity. Furthermore, patients with squamous cell esophageal cancers strongly expressing IGF2BP3 tended to respond poorly to chemoradiation. These data suggest that IGF2BP3 may be a key marker of radiosensitivity that diminishes the susceptibility of squamous cell esophageal cancer cells to radiotherapy. IGF2BP3 may, thus, be a useful target for improving radiotherapy for patients with esophageal squamous cell carcinoma.
Background
Conflicting results between bacterial mutagenicity tests (the Ames test) and mammalian carcinogenicity tests might be due to species differences in metabolism, genome structure, and DNA repair systems. Mutagenicity assays using human cells are thought to be an advantage as follow-up studies for positive results in Ames tests. In this collaborative study, a thymidine kinase gene mutation study (TK6 assay) using human lymphoblastoid TK6 cells, established in OECD TG490, was used to examine 10 chemicals that have conflicting results in mutagenicity studies (a positive Ames test and a negative result in rodent carcinogenicity studies).
Results
Two of 10 test substances were negative in the overall judgment (20% effective as a follow-up test). Three of these eight positive substances were negative after the short-term treatment and positive after the 24 h treatment, despite identical treatment conditions without S9. A toxicoproteomic analysis of TK6 cells treated with 4-nitroanthranilic acid was thus used to aid the interpretation of the test results. This analysis using differentially expressed proteins after the 24 h treatment indicated that in vitro specific oxidative stress is involved in false positive response in the TK6 assay.
Conclusions
The usefulness of the TK6 assay, by current methods that have not been combined with new technologies such as proteomics, was found to be limited as a follow-up test, although it still may help to reduce some false positive results (20%) in Ames tests. Thus, the combination analysis with toxicoproteomics may be useful for interpreting false positive results raised by 24 h specific reactions in the assay, resulting in the more reduction (> 20%) of false positives in Ames test.
We report 2 cases of small cell carcinoma of the esophagus treated with esophagectomy as a primary treatment and following chemotherapy. One patient (pT1N1M0) achieved long-term survival, while the other patient (pT1N1M1-lym) died 18 months after surgery. We used reports on 47 Japanese patients receiving esophagectomy as a primary treatment to determine when esophagectomy for small cell carcinoma of the esophagus is indicated. We conclude that esophagectomy as a local treatment provides relatively good long-term survival only in patients without lymph node involvement.
Summary
A new reference cigarette, 1R6F, produced by the Kentucky Tobacco Research and Development Center, has been manufactured as a substitute for the 3R4F reference cigarette because of a depletion of 3R4F stock. The purpose of the current study was to investigate the interchangeability of 1R6F and 3R4F by comparing the chemical and biological characteristics of the mainstream smoke and to assess the inter-laboratory reproducibility by comparing the results obtained in the current study with a previous report. We analyzed 45 priority chemicals required by Health Canada for regulatory reporting and assessed the toxicological effects of cigarette smoke using in vitro standard toxicological assays recommended by the Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA) under the International Organization for Standardization (ISO) standard and intense smoking regimens. The results of the chemical analysis and standard toxicological assays showed a good inter-laboratory reproducibility for 1R6F as a reference cigarette, while there were some slight reproducible differences between 1R6F and 3R4F. In addition, we investigated the interchangeability of 1R6F with 3R4F in some additional toxicological assays that detect oxidative stress because oxidative stress is a principle endpoint used in tobacco research with next generation tobacco and nicotine delivery products (NGPs). Both 1R6F and 3R4F elicited comparable responses in the oxidative stress assays. Overall, our results showed inter-laboratory reproducibility in chemical and standard toxicological assessments of 1R6F; thus, suggesting the suitability of 1R6F as a reference cigarette. In addition, the results obtained in the oxidative stress assays provide insight into the interchangeability of 1R6F with 3R4F when used as a comparator for NGPs.
Valores de parâmetros hematológicos de amostras sanguíneas de bovinos analisadas em diferentes intervalos de tempoValues of hematological parameters of bovine blood samples analyzed at different time
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