Cancer stem-like cells with increased expression of NY-ESO-1 initiate breast cancer metastasis.

Breast cancer stem-like cells (BCSLCs) with a CD44+/CD24-/low phenotype initiate the invasion and metastasis of breast cancer. The expression of New York oesophageal squamous cell carcinoma 1 (NY-ESO-1), one of the most immunogenic cancer-testicular antigens, is largely restricted to cancer and germ cells/placental trophoblasts, with little to no expression in normal adult somatic cells. Currently, few studies have reported the expression or function of NY-ESO-1 in BCSLCs. In the present study, immunohistochemistry indicated enhanced expression levels of NY-ESO-1/CD44 (P<0.01) and decreased expression levels of CD24 (P<0.01) in metastatic breast cancer tissues (MBCT) compared with non-MBCT. Additionally, the co-localization of CD44, CD24 and NY-ESO-1 in tissue samples was determined using immunofluorescence analysis. The results revealed that the expression of NY-ESO-1/CD44/CD24 was associated with breast cancer metastasis. Moreover, Spearman's rank correlation analysis indicated that CD44/CD24 expression was significantly correlated with that of NY-ESO-1. In the present study, mammosphere culture, a valuable method of BCSLC enrichment, was used to enrich MCF-7 and SK-BR-3 BCSLCs; immunofluorescence, western blotting and flow cytometry demonstrated increased expression levels of NY-ESO-1 and CD44, and low expression levels of CD24 in BCSLCs. Furthermore, the cell migration and invasion assays verified that BCSLCs with an increased NY-ESO-1 expression level exhibited greater invasive and migratory capacity compared with parental breast cancer cells. In addition to previously reported findings from the Oncomine database, it was ascertained that CD44+/CD24-/low BCSLCs with an increased level of NY-ESO-1 expression initiated the invasion and metastasis of breast cancer; therefore, NY-ESO-1 may serve as a novel target for metastatic breast cancer immunotherapy.

[Establishment of Reference Value of Hs-cTnT in Sichuan Region and Its Diagnostic Value in Patients with Chest Pain].

OBJECTIVE: To establish the reference value of high sensitive cardiac troponin T (hs-cTnT) and the efficiency of reference value in the diagnosis of chest pain. METHODS: Volunteers from eight independent communities in Chengdu,Sichuan were selected with detailed records of physical examination,electrocardiogram,ultrasound examination. The level of hs-cTnT for healthy volunteers was tested to determine ninety-ninth percentile references according to sex and ages. 2 249 patients with chest pain in the emergency department of Western China Hospital from July 2009 to July 2014 were enrolled to measure the efficiency of reference value for diagnosing acute myocardial infarction (AMI). RESULTS: There were 1 305 volunteers included finally. Among them,the mean hs-cTnT level of male was 4.3 (3.2-5.9) ng/L,which was significantly higher than that of female 3.0 (3.0-3.1) ng/L ( P<0.01) . The correlation coefficient between age and hs-cTnT level was 0.43 (male) and 0.29 (female),and the P-value was less than 0.01. The 99th percentile values of male were 10.8 ng/L,15.4 ng/L and 19.7 ng/L for <45 yr.,45-<60 yr. and ≥60 yr.,respectively. Those values of female were 4.6 ng/L,8.9 ng/L,18.8 ng/L,respectively. There was no difference in sensitivity and specificity between the value we figured out and manufactures provided (14.0 ng/L) for those<60 yr.. For the patients ≥60 yr.,the sensitivity and negative predictive value did not show diversity ( P>0.05) but the specificity and positive predictive value showed significant difference (male: 0.67 vs. 0.56 and 0.83 vs. 0.79, P<0.05;female:0.75 vs. 0.68 and 0.74 vs. 0.69, P<0.05). CONCLUSION: We recommends that the ninety-ninth percentile reference value of patients<60 yr. should be 14.0 ng/L,while 20.0 ng/L for those patients≥60 yr.

Diagnosis of Acute Myocardial Infarction in Hemodialysis Patients With High-Sensitivity Cardiac Troponin T Assay.

CONTEXT: Cardiac troponins have become the gold standard for diagnosing acute myocardial infarction (AMI) in the general population; however, their diagnostic accuracy for hemodialysis (HD) patients presenting with chest pain or dyspnea is uncertain. OBJECTIVE: To examine the diagnostic accuracy of high-sensitivity cardiac troponin T (hs-cTnT) assay for AMI in HD patients. DESIGN: In this prospective study, we enrolled 670 consecutive stable HD patients presenting with chest pain or dyspnea on routine predialysis therapy in the nephrology department. Receiver operating characteristic (ROC) curves were used to examine the diagnostic accuracy of hs-cTnT levels at enrollment in HD patients presenting with chest pain or dyspnea, and the dynamic change in these levels after 3 hours. RESULTS: Acute myocardial infarction was the adjudicated final diagnosis in 12% of HD patients. Among patients with a final diagnosis other than AMI, 97% had a plasma hs-cTnT concentration above the 99th percentile. At the time of enrollment, the area under the ROC curve of hs-cTnT levels for diagnosis of AMI was 0.68 (95% confidence interval [CI], 0.62-0.74; P < .001) with a cutoff value of 107.7 ng/L; the relative change after 3 hours was 0.90 (95% CI, 0.82-0.96, P < .001) with a cutoff value of 24%, and the absolute change was 0.88 (95% CI, 0.82-0.94, P < .001) with a cutoff value of 32.6 ng/L. The prognostic value for 40-day mortality varied with the magnitude of elevation in hs-cTnT levels. CONCLUSIONS: Tracking the dynamic change in hs-cTnT levels during the short term significantly increased this measure's diagnostic accuracy for AMI in HD patients.

High-Sensitivity Cardiac Troponin T in Patients with Acute Myocardial Infarction in Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

BACKGROUND: In clinical work, patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) often have high-sensitivity cardiac troponin T (hs-cTnT) levels that surpass the 99th percentile of the normal reference population, a cutoff used to screen patients for acute myocardial infarction (AMI). However, a large proportion of these patients prove not to have AMI and are frequently misdiagnosed and overtreated. We analyzed whether the cutoff value of hs-cTnT for diagnosing AMI in AECOPD patients should be adjusted. METHODS: This was a prospective study of 873 consecutive patients with AECOPD who presented at the emergency department of West China Hospital of Sichuan University from January 2010 to December 2013. Conventional cardiac troponin (cTnT) was measured in patients' blood samples taken at presentation, and values were compared with their final diagnoses. RESULTS: Among patients with a final diagnosis other than AMI, 64.64% had a plasma hs-cTnT concentration above the 99th percentile of a normal reference population (14 ng/L). The median level of hs-cTnT in AECOPD patients without AMI was 16 ng/L. The area under the receiver-operating characteristic curve (AUC) of hs-cTnT for diagnosis of AMI was 0.92 (0.85 - 0.99, p < 0.001) with a cutoff value of 60.5 ng/L. CONCLUSIONS: The baseline levels of hs-cTnT were relatively high in AECOPD patients, and the optimal cutoff value of hs-cTnT for AMI diagnosis (60.5 ng/L) was also higher than that for non-AECOPD patients.

Procalcitonin levels predict acute kidney injury and prognosis in acute pancreatitis: a prospective study.

BACKGROUND: Acute kidney injury (AKI) has been proposed as a leading cause of mortality for acute pancreatitis (AP) patients admitted to the intensive care unit (ICU). This study investigated the predictive value of procalcitonin (PCT) for AKI development and relevant prognosis in patients with AP, and compared PCT's predictive power with that of other inflammation-related variables. METHODS: Between January 2011 and March 2013, we enrolled 305 cases with acute pancreatitis admitted to ICU. Serum levels of PCT, serum amyloid A (SAA), interleukin-6 (IL-6), and C reactive protein (CRP) were determined on admission. Serum PCT was tested in patients who developed AKI on the day of AKI occurrence and on either day 28 after occurrence (for survivors) or on the day of death (for those who died within 28 days). RESULTS: Serum PCT levels were 100-fold higher in the AKI group than in the non-AKI group on the day of ICU admission (p<0.05). The area under the receiver-operating characteristic (ROC) curve of PCT for predicting AKI was 0.986, which was superior to SAA, CRP, and IL-6 (p<0.05). ROC analysis revealed all variables tested had lower predictive performance for AKI prognosis. The average serum PCT level on day 28 (2.67 (0.89, 7.99) ng/ml) was significantly (p<0.0001) lower than on the day of AKI occurrence (43.71 (19.24,65.69) ng/ml) in survivors, but the serum PCT level on death (63.73 (34.22,94.30) ng/ml) was higher than on the day of AKI occurrence (37.55 (18.70,74.12) ng/ml) in non-survivors, although there was no significant difference between the two days in the latter group (p = 0.1365). CONCLUSION: Serum PCT is superior to CRP, IL-6, and SAA for predicting the development of AKI in patients with AP, and also can be used for dynamic evaluation of AKI prognosis.