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We investigated the prognostic significance of circulating tumor cells (CTCs) determined immediately before the second cycle of chemotherapy in patients with metastatic breast cancer (MBC). The CTC counts were taken at baseline, before the first cycle of chemotherapy (CTC-0), and on day 21 before commencing the second cycle of chemotherapy (CTC-21) in consecutive MBC patients. The study's primary objectives were to analyze relationships between CTC-21 count and overall survival (OS). Based on the current literature, the CTC measurements were dichotomized as 0 -4 versus Ն5 CTCs. Of 117 patients recruited, 99 were evaluable. Patients with 0 -4 CTCs on day 21 had a significantly better OS than those with Ն5 CTCs (median OS: 38.5 months vs. 8.7 months). They also had a significantly better progression-free survival (PFS; median: 9.4 months vs. 3.0 months) and clinical benefit rate (77% vs. 44%). The OS of patients whose baseline CTCs were Ն5 but dropped to Ͻ5 on day 21 was apparently similar to those who had Ͻ5 CTCs at baseline. In a Cox regression analysis, CTC-21 was the only independent variable significantly predicting OS and PFS. Our data indicate that CTCs determined immediately before the second cycle of chemotherapy is an early and strong predictor of treatment outcome in MBC patients. The Oncologist 2013;18:917-923 Implications for Practice: We investigate the prognostic significance of circulating tumor cells (CTCs) immediately before administering the second cycle of a chemotherapy regimen in patients with metastatic breast cancer. Patients with 0 -4 CTCs on day 21 (regardless the baseline CTC count) had a significantly better PFS and OS than those with Ն5 CTCs. In a Cox regression analysis, CTC-21 was the only independent variable significantly predicting OS (p ϭ .009) and PFS (p ϭ .047). Our study suggests that CTCs count determined immediately before the second cycle of chemotherapy is an early, and strong, predictor of treatment outcome in MBC patients, since it can identify those patients who derive little benefit from the chemotherapy regimen and also have a poor prognosis with conventional treatment. INTRODUCTIONThe detection and enumeration of circulating tumor cells (CTCs) in patients with metastatic breast cancer (MBC) is currently undergoing intense investigation. Several studies have shown that the number of CTCs at baseline is an independent predictor of progression-free survival (PFS) and overall survival (OS) in MBC patients [1][2][3][4]. The U.S. Food and Drug Administration has approved a semiautomated immunomagnetic method, the CellSearch system (Veridex, LLC, Warren, NJ, https://www.cellsearchctc.com/), specifically for this purpose. CTC enumeration using the CellSearch system appears to be a reproducible method. In a previous study, we did not observe any significant intrapatient variability in CTCs in two

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Serum FGF23 concentrations remain increased in long-term kidney graft recipients, even in the early stages of CKD. It remains to be seen whether measures aimed at reducing serum levels of PTH and phosphate and/or corticosteroid doses might help to lower serum FGF23 and whether this will improve kidney recipient outcomes.

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The aim of this study was to determine the frequency of p16 and hMLH1 genes simultaneous methylation in colorectal cancer patients with Microsatellite Instability (MSI) tumors. We also wanted to analyze the relationship with other clinical features, with BRAF gene V600E mutation and with prognosis. Samples from fifty one patients with MSI positive sporadic colorectal cancer were included. DNA was extracted from tumor samples. Promoter methylation was analyzed using bisulfite modification and was detected by quantitative methylation-specific PCR. BRAF gene was amplified using specific primers and mutations were detected by real time PCR. Simultaneous methylation was transformed in a new variable called CMETH2. Frequency of CMETH2 was analyzed and compared with other clinicopathological variables. 33.3 % of patients were positive for CMETH2 and 25 % had BRAF V600E mutation. CMETH2 was related with proximal location, with poorly differentiated tumors and with BRAF V600E mutation. CMETH2 only showed influence in the overall survival (OS) in patients with distal tumors. However, with regard to the disease free survival (DFS) measure, CMETH2 was independent prognostic factor. We were able to discriminate tumors with high methylation features using a transformation analysis of variables into a new computed one (CMETH2). CMETH2 has demonstrated to be a useful prognostic factor in MSI tumors. The prognostic value of CMETH2 in DFS was independent of other clinicopathological variables. The use of CMETH2 could help in the election of the best therapeutic alternative for CCR patients with MSI tumors.

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According to this study, mutations in different exons of p53 are related to different phenotypes in colorectal cancer. These phenotypes could mean differences in the clinical evolution of the patients.