Colorectal cancer (CRC) is a mortal disease due to treatment resistance, recurrence and distant metastasis. Emerging evidence has revealed that a small sub-population of cancer cells termed cancer stem cells (CSCs)/ cancer-initiating cells (CICs) is endowed with high levels of tumor-initiating ability, self-renewal ability and differentiation ability and is responsible for treatment resistance, recurrence and distant metastasis. Eradication of CSCs/CICs is essential to improve current treatments. However, the molecular mechanisms by which CSCs/CICs are maintained are still elusive. In this study, we aimed to determine the molecular mechanisms by which colorectal (CR)-CSCs/CICs in are maintained human primary CRC cells. CR-CSCs/CICs were isolated by sphere-culture and the ALDEFLUOR assay, and transcriptome analysis revealed that the gene ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) was expressed at high levels in CR-CSCs/CICs. Overexpression of ST6GALNAC1 enhanced the expression of sialyl-Tn (STn) antigen, which is carried by the CSC marker CD44, and increased the sphere-forming ability and resistance to a chemotherapeutic reagent. The opposite phenomena were observed by gene knockdown using siRNA. Furthermore, the Akt pathway was activated in ST6GANAC1-overexpressed cells, and activation of the pathway was cancelled by gene knockdown of galectin-3. The results indicate that ST6GALNAC1 has a role in the maintenance of CR-CSCs/CICs by activating the Akt pathway in cooperation with galectin-3 and that ST6GalNAC1 (or STn antigen) might be a reasonable molecule for CSC/CIC-targeting therapy.
BackgroundThe low anterior resection syndrome (LARS) score is a patient-reported outcome measure to evaluate the severity of bowel dysfunction after rectal cancer surgery by scoring the major symptoms of LARS. The aim of this study was to translate the English version of the LARS score into Japanese and to investigate the validity and reliability of the LARS score.MethodsThe LARS score was translated in Japanese following current international recommendations. A total of 149 rectal cancer patients completed the LARS score questionnaire and were also asked a single question assessing the impact of bowel function on quality of life (QoL). A total of 136 patients answered the LARS score questionnaire twice.ResultsThe Japanese LARS score showed high convergent validity, based on its good correlation between the LARS score and QoL (p < 0.001). The LARS score was able to discriminate between patients according to the tumor distance to anal verge (p < 0.001), type of surgery (p < 0.001), and time since surgery (p = 0.001). Patients after ultra-low anterior resection and intersphincteric resection showed especially high scores. The score also had high test–retest reliability (intraclass correlation coefficient: 0.87).ConclusionThe Japanese LARS score is a valid and reliable tool for measuring LARS. The LARS score is appropriate for assessments in postoperative bowel function and international comparison. Using this score, patient-reported outcome measures of LARS in Japanese patients can be shared internationally. Additional validation reports from non-English speaking countries can support the LARS score as a worldwide assessment tool for postoperative bowel dysfunction.
Background Accurate identification of tumor sites during laparoscopic colorectal surgery helps to optimize oncological clearance. We aimed to assess the timing of the local injection preoperatively and clarify the usefulness and limitation of tumor site marking using indocyanine green (ICG) fluorescence imaging. Methods Consecutive patients who underwent primary colorectal cancer surgery from September 2017 to January 2019 were included. Preoperatively, lower endoscopy was used to inject the ICG solution into the submucosal layer near the tumor. During laparoscopic surgery, ICG fluorescence marking as the tumor site marking was detected using a laparoscopic near-infrared camera system. The detection rate and factors associated with successful intraoperative ICG fluorescence visualization including the interval between local injection and surgery were evaluated. Results One hundred sixty-five patients were enrolled. Using the laparoscopic near-infrared system, the intraoperative detection rates of ICG marking were 100% for ICG injection within 6 days preoperatively, 60% for injection between 7 and 9 days preoperatively, and 0% for injection earlier than 10 days preoperatively. There were no complications associated with ICG marking. Additionally, this method did not disturb the progress of the surgical procedure because injected ICG in the submucosal layer did not cause any tissue inflammation, and if ICG spilled into the serosa, it was invisible by white light. Conclusion Advantages of ICG fluorescence tumor site marking were high visibility of infrared imaging during laparoscopic colorectal surgery and minimal adverse events of surgery. One of the most important findings regarding practical use was a rapid decrease in fluorescence marking visibility if one week passed from the time of ICG local injection.
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