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Peer Reviewed Papers, Books, Chapters

Year Title Citation Authors Review type Summary Keywords File filename File mime type
1. BACKGROUND: To investigate the prognostic value of the log odds of positive lymph nodes (LODDS) in patients with advanced esophageal squamous cell carcinoma (ESCC) after surgical resection. Pubmed BACKGROUND: To investigate the prognostic value of the log odds of positive lymph nodes (LODDS) in patients with advanced esophageal squamous cell carcinoma (ESCC) after surgical resection. METHODS: Clinical data of 260 patients with advanced ESCC undergoing surgical resection were retrospectively reviewed. Univariate and multivariate analysis were done using the chi-square test and Cox regression model. Receiver-operating-characteristic (ROC) curve was used to compare the association of pathologic nodal (pN) and LODDS with 3- or 5-year overall survival (OS). The cut-point analyses were performed to determine whether there was a cutoff LODDS related to the greatest OS difference. RESULTS: The mean follow-up duration was 30 months (range, 3 to 106 months). The 1-, 3-, 5-year OS rates were 70.0%, 41.9% and 30.3%, respectively. Univariate analyses indicated that the 5-year OS rates were 51.2%, 30.5%, 24.6%, and 14.2% in LODDS1, LODDS2, LODDS3, and LODDS4, respectively, and the median survival times were 68.7, 34.6, 24.0, and 14.6 months, respectively (P=0.000) for all patients, and subgroup analysis showed the effect did not change in 155 patients without lymph node (LN) metastasis (P=0.024). Multivariate analysis showed that LODDS [hazard ratio (HR) =1.309, P=0.003] to be independent and significant prognostic factors for all patients, so as in node-negative patients LODDS (HR =1.610, P=0.038). The AUC of LODDS stage (AUC =0.630) was larger than that of pN stage (AUC =0.621) in prediction of 3-year OS, however LODDS were smaller in prediction of 5-year OS (AUC =0.620, 0.631, respectively), and the differences were not statistically significant (P>0.05 all). Lastly, the step analysis identified the best cut-off point for LODDS as -1.2 that is significantly associated with the prognosis of the node-negative patients (P=0.024), and the ROC analysis also indicated that a cut-off value of -1.2 for LODDS provided the highest sensitivity and specificity interestingly. CONCLUSIONS: LODDS may be suitable for evaluation of OS in advanced ESCC patients without LN metastasis. Log odds of positive lymph nodes (LODDS); esophagus neophagus; prognosis
2. Cisplatin is one of the most commonly used chemotherapeutic drugs; however, toxicity and tumor resistance limit its use. Pubmed Cisplatin is one of the most commonly used chemotherapeutic drugs; however, toxicity and tumor resistance limit its use. Studies using murine models and human subjects have shown that the time of day of cisplatin treatment influences renal and blood toxicities. We hypothesized that the mechanisms responsible for these outcomes are driven by the circadian clock. We conducted experiments using wild-type and circadian disrupted Per1/2-/- mice treated with cisplatin at selected morning (AM) and evening (PM) times. Wild-type mice treated in the evening showed an enhanced rate of removal of cisplatin-DNA adducts and less toxicity than the morning-treated mice. This temporal variation in toxicity was lost in the Per1/2-/- clock-disrupted mice, suggesting that the time-of-day effect is linked to the circadian clock. Observations in blood cells from humans subjected to simulated day and night shift schedules corroborated this view. Per1/2-/- mice also exhibited a more robust immune response and slower tumor growth rate, indicating that the circadian clock also influences the immune response to melanoma tumors. Our findings indicate that cisplatin chronopharmacology involves the circadian clock control of DNA repair as well as immune responses, and thus affects both cisplatin toxicity and tumor growth. This has important implications for chronochemotherapy in cancer patients, and also suggests that influencing the circadian clock (e.g., through bright light treatment) may be explored as a tool to improve patient outcomes. DNA repair; circadian rhythm; cisplatin; melanoma; toxicity


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