Exosomes play important roles in cancer progression. Although its contents (e.g., proteins and microRNAs) have been focused on in cancer research, particularly as potential diagnostic markers, the exosome behavior and methods for exosome quantification remain unclear. In the present study, we analyzed the tumor-derived exosome behavior and assessed the quantification of exosomes in patient plasma as a biomarker for esophageal squamous cell carcinoma (ESCC). A CD63-GFP expressing human ESCC cell line (TE2-CD63-GFP) was made by transfection, and mouse subcutaneous tumor models were established. Fluorescence imaging was performed on tumors and plasma exosomes harvested from mice. GFP-positive small vesicles were confirmed in the plasma obtained from TE2-CD63-GFP tumor-bearing mice. Patient plasma was collected in Chiba University Hospital (n=86). Exosomes were extracted from 100 µl of the plasma and quantified by acetylcholinesterase (AChE) activity. The relationship between exosome quantification and the patient clinical characteristics was assessed. The quantification of exosomes isolated from the patient plasma revealed that esophageal cancer patients (n=66) expressed higher exosome levels than non-malignant patients (n=20) (P=0.0002). Although there was no correlation between the tumor progression and the exosome levels, exosome number was the independent prognostic marker and low levels of exosome predicted a poor prognosis (P=0.03). In conclusion, exosome levels may be useful as an independent prognostic factor for ESCC patients.
Abstract Background: ESCC(Esophageal Squamous Cell Carcinoma) is highly aggressive due to its tendency to metastasize to the lymph nodes and organs. Our laboratory previously reported that the exosome amount in the peripheral blood could predict the prognosis of ESCC patients. CD63 is a tetraspanin family protein and is often used as a marker of exosome.CD63 highly express in early stage melanoma and thought to be a suppressive factor against EMT (epithelial-to-mesenchymal transition) in melanoma. On the other hand, some report confirmed CD63 as a prometastatic factor via regulating E cadherin expression. The function of CD63 are still controversial. We herein assessed CD63 expression and clinicopathological findings in ESCCpatient, and assessed molecular roles of CD63 in ESCC cell lines. Materials and methods: The relationship between the CD63 expression in the resected ESCC specimen (from 1997 to 2006, n=86) and clinicathological features were assessed using immunohistochemical staining. Human ESCC cell lines (TE2,TE15) were used as high CD63 expression cell lines for in vitro analysis. CD63 was knockdown using siRNA, and CD63 down regulate was confirmed by western blot and PCR. The influence on the cell behavior and gene expressions were assessed by cell proliferation assay, mRNA microarray, and GSEA(Gene Set Enrichment Analysis). Results: There were no statistically significant correlation between the CD63 expression and age, sex, tumor depth (T), lymph node metastasis (N), distant organ metastasis (M), differentiation of tumor, lymphatic vessel invasion (ly), venous invasion (v), the type of progression. As for the prognosis, the high CD63 expression patients have significantly poorer prognosis than the low expression of CD63 patients. (P=0.047, log rank test). In vitro study, cell proliferation assay showed down expression of CD63 reduce cell proliferation. Knock down of CD63 downregulates HER2 expression and influence on other ERBB signaling pathways. Conclusions: High CD63 expression predicts poor prognosis in human ESCC. The molecular function of CD63 could have relationship to ERBB signaling pathways in human ESCC cells. Citation Format: Yasunori Matsumoto, Masayuki Kano, Kentaro Murakami, Satoshi Endo, Takeshi Toyozumi, Tadashi Shiraishi, Toshiki Kamata, Takahiro Ryuzaki, Kazuya Kinoshita, Soichiro Hirasawa, Hisahiro Matsubara. Clinical significance of tetraspanin CD63 in human ESCC [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5444.
Identifying accurate biomarkers for predicting response to chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC) is a critical challenge. The protein SIRT1, recognized for its implications in longevity, has been associated with tumor promotion in ESCC. However, data regarding its correlation with CRT sensitivity remain unreported. Therefore, in this study, we aimed to investigate the relationship between SIRT1 expression and CRT sensitivity and concurrently assess the effect of SIRT1 knockdown on CRT sensitivity in ESCC.
We aim to quantitatively evaluate stress tolerance based on EEG. Stress tolerance is defined as resistance capability and recover ability. We measure stress tolerance of stressing subjects with white puzzle task. The questionnaire answered was compared with the measurement result of stress tolerance. Experimental results show the correlation between the recovering ability and the questionnaire.
Abstract:Esophageal cancer is one of the most serious digestive cancers with a poor prognosis.The esophagus is a long, thin organ extending from the neck to the mediastinum, with wide regional lymph nodes.In addition, confirming the extent of lymph node metastasis is an important factor in predicting the prognosis of patients.In this study, we investigate a method for automatically detecting lymph nodes and discriminating between it has metastasis or not by using a machine learning from chest contrast-enhanced X-ray CT images.In experiments, the sensitivity and specificity were 80% and 100%.However, the number of cases studied and the number of lymph node metastases were small, it is necessary to increase the number of cases to evaluate the effectiveness.
Abstract Background Esophagostomy is important in the treatment of esophageal cancer. However, esophagectomy has a higher risk of postoperative complications. Treatment for complications is often difficult, and in some cases, oral intake is no longer possible. Recently, magnetic compression anastomosis (MCA) was developed; it is a relatively safe method of anastomosis that does not require surgery in patients with stricture, obstruction, or dehiscence of the anastomosis after surgery. Case presentation The patient was a 76-year-old Japanese man. He underwent esophagectomy with a three-field dissection for esophageal cancer. A cervical esophagostomy and chest drainage were performed for necrosis of the gastric tube. Following infection control, colon interposition was performed. However, after the operation, the colon necrotized and formed an abscess. Drainage controlled the infection, but the colon was completely obstructed. The patient was referred to our hospital to restore oral ingestion. Contrast studies showed that the length of the occlusion was 10 mm. The reconstruction was examined; reanastomosis by surgery was judged to be a high risk, so the strategy of anastomosis by MCA was adopted. In the operation, the anterior chest was opened to expose the colon, and a magnet was inserted directly into the blind end of the colon. The magnet was guided to the blind end of the esophagus using an oral endoscope. Two weeks after MCA, a contrast study confirmed the passage of the contrast agent from the esophagus to the colon. The patient eventually took 18 bougies after the MCA. However, since then, he has not needed a bougie. As of 1 year and 8 months after the MCA, the patient is living at home with oral intake restored. Conclusions MCA is an effective and safe treatment for complete stenosis after esophageal cancer surgery.
Background Seasonal variations could systematically bias dietary intakes. This systematic review aimed to determine seasonal variations in dietary intake among Japanese adults.
<b><i>Introduction:</i></b> We determined the soluble programmed cell death-1 ligand-1 (sPD-L1) concentration in patients with esophageal squamous cell carcinoma (ESCC), and confirmed the PD-L1 expression in resected specimens. <b><i>Methods:</i></b> Blood samples were collected from 73 patients with histologically proven ESCC. The serum levels of sPD-L1 were measured using an enzyme-linked immunosorbent assay. The correlations between the sPD-L1 concentration and the expression of PD-L1 in tumor specimens and tumor depth, lymph node metastasis, disease stage, and various laboratory data were assessed. <b><i>Results:</i></b> sPD-L1 levels in patients with high PD-L1 expression levels in tumor tissue were significantly higher than in patients with low PD-L1 expression levels (<i>p</i> = 0.042). The OS of the sPD-L1-high group was significantly worse than that of the low group (<i>p</i> = 0.028). Similarly, patients in whom a tissue specimen was PD-L1-positive group showed significantly poorer OS. <b><i>Conclusion:</i></b> The sPD-L1 concentration was correlated with the PD-L1 expression in tissues. Patients with PD-L1-positive tissue specimens showed significantly higher sPD-L1 levels in comparison to PD-L1-negative cases. Furthermore, patients with high sPD-L1 expression levels had a significantly worse prognosis than those with low sPD-L1 expression levels, and patients with a PD-L1-positive tissue specimen had a significantly worse prognosis than patients in whom the tissue specimen showed a low PD-L1 expression level.