Correction: Galectin-3 as a Marker and Potential Therapeutic Target in Breast Cancer.

[This corrects the article DOI: 10.1371/journal.pone.0103482.].

Effects of Srxn1 on growth and Notch signalling of astrocyte induced by hydrogen peroxide.

OBJECTIVE: To investigate the effect of Sulfiredoxin-1 (Srxn1) on astrocyte injury induced by hydrogen peroxide (H2O2). METHODS: Observing the changes of H2O2 on contents of lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD) and apoptosis after transfected Srxn1 siRNA into astrocytes. The protein expression of Notch 1, NICD and Hes1, the content of LDH and MDA, the activity of SOD and apoptosis rate of astrocytes after inhibiting or activation of Notch signalling pathway were detected by Western blot, ELISA and flow cytometry, respectively. RESULTS: Knockdown of Srxn1 could promote the secretion of LDH and MDA, decrease the activity of SOD and aggravate apoptosis of astrocytes induced by H2O2. The results of Western blot, ELISA assay and flow cytometry indicated that activation of the Notch signalling pathway attenuated the effect of Srxn1 on H2O2-induced oxidative damage and apoptosis of astrocytes. CONCLUSION: Srxn1 may protect astrocytes from oxidative stress injury induced by H2O2 by activation of Notch signalling pathway.

The prognostic efficacy of the 8th edition UICC TNM classifications for gastric cancer in Chinese patients: A study based on follow-up system of nursing department.

This study aimed to analyze the applicability of the Union for International Cancer Control (UICC) tumor-node-metastasis (TNM) classification 8th edition for Chinese patients with gastric cancer.A review of all inpatient and outpatient records of patients with gastric cancer was conducted in the First Affiliated Hospital of China Medical University and Liaoning Cancer Hospital and Institute. All patients who met the inclusion criteria and were seen from January 1980 through December 2009 were included in the study. The primary outcome was 5-year survival, which was analyzed according to the decade of diagnosis and TNM classifications.Two thousand five hundred fifty-four patients were enrolled in this study. When classified according to the UICC TNM classification of gastric cancer 8th edition, the prognoses of patients with stage IIIB (n = 250) and stage IIIC (n = 101) disease were not significantly different (P = .332). However, if T4aN2 patients were classified as having stage IIIB disease, and T4bN2 and T4aN3a patients were classified as having stage IIIC disease, the prognoses of stage IIIB (n = 221) and stage IIIC (n = 172) patients were significantly different (P = .03).Classifying T4bN0 patients as having stage IIIB disease, and T4bN2 and T4aN3a patients as having stage IIIC disease according to the 8th edition of UICC gastric cancer TNM classifications better stratified Chinese patients and predicted prognoses.

Improvements to the gastric cancer tumor-node-metastasis staging system based on computer-aided unsupervised clustering.

BACKGROUND: The Union for International Cancer Control (UICC) tumor-node-metastasis (TNM) classification is a key gastric cancer prognosis system. This study aimed to create a new TNM system to provide a reference for the clinical diagnosis and treatment of gastric cancer. METHODS: A review of gastric cancer patients' records was conducted in The First Hospital of China Medical University and the Liaoning Cancer Hospital and Institute. Based on patients' prognoses data, computer-aided unsupervised clustering was performed for all possible TNM staging situations to create a new staging division system. RESULTS: The primary outcome measure was 5-year survival, analyzed according to TNM classifications. Computer-aided unsupervised clustering for all TNM staging situations was used to create TNM division criteria that were more consistent with clinical situations. Furthermore, unsupervised clustering for the number of lymph node metastasis in the N stage led to the formulation of a classification method that differs from the existing N stage criteria, and unsupervised clustering for tumor size provided an additional reference for prognosis estimates. CONCLUSIONS: Finally, we developed a TNM staging system based on the computer-aided unsupervised clustering method; this system was more in line with clinical prognosis data when compared with the 7th edition of UICC gastric cancer TNM classification.

A similarity measure method combining location feature for mammogram retrieval.

BACKGROUND: Breast cancer, the most common malignancy among women, has a high mortality rate in clinical practice. Early detection, diagnosis and treatment can reduce the mortalities of breast cancer greatly. The method of mammogram retrieval can help doctors to find the early breast lesions effectively and determine a reasonable feature set for image similarity measure. This will improve the accuracy effectively for mammogram retrieval. METHODS: This paper proposes a similarity measure method combining location feature for mammogram retrieval. Firstly, the images are pre-processed, the regions of interest are detected and the lesions are segmented in order to get the center point and radius of the lesions. Then, the method, namely Coherent Point Drift, is used for image registration with the pre-defined standard image. The center point and radius of the lesions after registration are obtained and the standard location feature of the image is constructed. This standard location feature can help figure out the location similarity between the image pair from the query image to each dataset image in the database. Next, the content feature of the image is extracted, including the Histogram of Oriented Gradients, the Edge Direction Histogram, the Local Binary Pattern and the Gray Level Histogram, and the image pair content similarity can be calculated using the Earth Mover's Distance. Finally, the location similarity and content similarity are fused to form the image fusion similarity, and the specified number of the most similar images can be returned according to it. RESULTS: In the experiment, 440 mammograms, which are from Chinese women in Northeast China, are used as the database. When fusing 40% lesion location feature similarity and 60% content feature similarity, the results have obvious advantages. At this time, precision is 0.83, recall is 0.76, comprehensive indicator is 0.79, satisfaction is 96.0%, mean is 4.2 and variance is 17.7. CONCLUSIONS: The results show that the precision and recall of this method have obvious advantage, compared with the content-based image retrieval.

Predicting level 2 axillary lymph node metastasis in a Chinese breast cancer population post-neoadjuvant chemotherapy: development and assessment of a new predictive nomogram.

BACKGROUND: We aimed to develop a new nomogram to predict the probability of level 2 axillary lymph node metastasis (L-2-ALNM) in breast cancer (BC) patients treated with neoadjuvant chemotherapy (NAC). METHODS: Data were collected from 709 patients who received neoadjuvant chemotherapy and then underwent axillary lymph node (ALN) dissection between May 2009 and December 2015 at the Liaoning Cancer Hospital. The level 2 axillary lymph node metastasis (L-2-ALNM ) nomogram was created from the logistic regression model. An additional set of 141 consecutive patients treated at the same institution between January 2015 and December 2015 were enrolled as the validation group. The predictive accuracy of the L-2-ALNM nomogram was measured by calculating the area under the receiver operating characteristic curve (AUC). RESULTS: In multivariate analysis, age, tumor size, histological grade, skin invasion, and response to neoadjuvant chemotherapy were identified as independent predictors of L-2-ALNM. The new model was accurate and discriminating for both the modeling and validation groups (AUC: 0.819 vs 0.849). The false-negative rates of the L-2-ALNM nomogram were 4.44% and 7.69% for the predicted probability cut-off points of 10% and 20%. CONCLUSION: The L-2-ALNM nomogram shows reasonable accuracy for making clinical decisions. The omission of level 2 axillary lymph node dissection after neoadjuvant chemotherapy might be possible if the probability of level 2 lymph node involvement was < 10% or < 20% in accordance with the acceptable risk determined by medical staff and patients.

Prognostic significance of GSTP1 in patients with triple negative breast cancer.

BACKGROUND: Previous studies showed that glutathione S-transferase Pi 1 (GSTP1) is a critical metabolic driver that is heightened specifically in triple negative breast cancer (TNBC) and drives breast cancer pathogenicity. This study focuses on investigating the relationship between the expression of the GSTP1 protein and TNBC metastasis and prognosis in China. RESULTS: Chi-square and Fisher's exact tests showed that tumor size (P=0.023) and clinical stage (P=0.049) were significantly associated with GSTP1 expression. Patients with high GSTP1 expression exhibited an improved survival rate compared with patients with low GSTP1 expression, but the difference was not statistically significant (P=0.437). On multivariate analysis, clinical stage proved to be an independent prognostic factor for survival in breast cancer. MATERIALS AND METHODS: A total of 175 patients with histologically confirmed TNBC, who also underwent radical surgery between January 2008 and November 2011 at the Liaoning Cancer Hospital, were enrolled. Immunohistochemistry was used to detect GSTP1 expression in breast cancer tissue from 175 patients. The correlations between GSTP1 expression and other parameters were evaluated using the Chi-square and Fisher's exact tests. Univariate and multivariate Cox regression analyses were performed to assess independent prognostic factors for survival. Associations of GSTP1 expression with clinical stage and prognosis were analyzed using Kaplan-Meier survival curves. CONCLUSIONS: Tumors with high GSTP1 protein expression were independently associated with low clinical stages in TNBC patients in China. The expression of the GSTP1 protein may be a novel prognosis marker for TNBC patients in China.

Overexpression of let-7a increases neurotoxicity in a PC12 cell model of Alzheimer's disease via regulating autophagy.

Increased deposition of ß-amyloid (Aß) protein is one of the typical characteristics of Alzheimer's disease (AD). Recent evidence has demonstrated that the microRNA let-7 family, which is highly expressed in the central nervous system, participates in the regulation of pathologic processes of AD. In the present study, the effect of let-7a overexpression on Aß1-40-induced neurotoxicity was evaluated in PC12 and SK-N-SH cells. The results indicated that overexpression of let-7a enhanced the neurotoxicity induced by Aß1-40 in PC12 and SK-N-SH cells. In addition, the apoptosis induced by Aß1-40 in PC12 and SK-N-SH cells was increased by let-7a overexpression. Furthermore, Aß1-40 treatment increased the protein levels of microtubule-associated protein 1A/1B-light chain 3 (LC3) and beclin-1 and increased the LC3 II/I ratio. The mRNA expression levels of beclin-1, autophagy protein 5 (Atg-5) and Atg-7 were also increased by Aß1-40 treatment in PC12 cells. Let-7a overexpression further upregulated the above autophagy-related markers. Furthermore, the protein level of p62 was increased by Aß1-40 treatment, and this was further enhanced by let-7a overexpression. Finally, the present results demonstrated that the phosphoinositide-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway was involved in the autophagy regulation by let-7a. In conclusion, the present study demonstrates that the neurotoxicity induced by Aß1-40 is augmented by let-7a overexpression via regulation of autophagy, and the PI3K/Akt/mTOR signaling pathway also serves a function in this process.

Prognostic significance of subclassification of stage IIB lung cancer: a retrospective study of 226 patients.

We investigated the prognostic significance of subclassification of stage IIB lung cancer according to the eighth tumor-node-metastasis (TNM) classification. To this purpose, the prognostic outcomes of 226 stage IIB lung cancer patients who underwent surgery without adjuvant therapies between 2001 and 2010 were evaluated retrospectively based on the eighth TNM classification. Of the 226 patients, 23, 30, 118 and 55 had pT1b, pT1c, pT2a, and pT2b stage cancers, respectively. Their 5-year survival rates were 67%, 33%, 21%, and 27%, respectively. There was no significant difference in the 5-year survival between T1b and T1c, between T1c and T2a, and between T2a and T2b (p = 0.128, 0.105, and 0.403, respectively). There were significant differences in the 5-year survival between T1b and T2a, between T1b and T2b, and between T1c and T2b (p = 0.005, 0.002, and 0.042, respectively). The 5-year survival of patients with pleural invasion and vessel invasion was significantly worse than that of their counterparts (p = 0.009 and <0.001, respectively). Subclassification of stage IIB lung cancer is of prominent prognostic significance. It is recommended that the current stage be subclassified, in order to more accurately predict the prognosis of patients.

The prognostic efficacy and improvements of the 7th edition Union for International Cancer Control tumor-node-metastasis classifications for Chinese patients with gastric cancer: Results based on a retrospective three-decade population study.

This study aimed to evaluate survival trends for patients with gastric cancer in northeast China in the most recent three decades and analyze the applicability of the UICC tumor-node-metastasis (TNM) classification 7th edition for Chinese patients with gastric cancer. A review of all inpatient and outpatient records of patients with gastric cancer was conducted in the first hospital of China Medical University and the Liaoning Cancer Hospital and Institute. All patients who met the inclusion criteria and were seen from January 1980 through December 2009 were included in the study. The primary outcome was 5-year survival, which was analyzed according to decade of diagnosis and TNM classifications. From 1980 through 2009, the 5-year survival rates for patients with gastric cancer (n=2414) increased from 39.1% to 57.3%. Decade of diagnosis was significantly associated with patient survival (p = 0.013), and the 5-year survival rate in the 2000s was remarkably higher than that in the 1980s and 1990s (p = 0.004 and 0.049, respectively). When classified according to the UICC TNM classification of gastric cancer 7th edition, the prognoses of stage IIIA and stage IIIB patients were not significantly different (p = 0.077). However, if stage T4b and stage N0 patients were classified as stage IIIA, the prognoses of stage IIIA and stage IIIB patients were significantly different (p < 0.001). Hence, there was a significant difference in survival during the three time periods in Northeast China. Classifying stage T4b and stage N0 patients as stage IIIA according to the 7th edition of UICC gastric cancer TNM classifications better stratified Chinese patients and predicted prognoses.

EZH2 mediates ATO-induced apoptosis in acute myeloid leukemia cell lines through the Wnt signaling pathway.

In this study, we examined the mechanisms associated with EZH2 mediation of apoptosis and chemoresistance to arsenic trioxide (ATO) in acute myeloid leukemia (AML) cell lines through the Wnt/ß-catenin signaling pathway. The induction of spontaneous apoptosis observed in multiple EZH2-silenced leukemic cell lines was assessed by flow cytometry, and levels of Wnt/ß-catenin-related expression were determined by western blot analysis. In comparison with AML control cells, EZH2-knockdown cells exhibited increased apoptosis and significant downregulation of ß-catenin expression, as well as decreases in GSK-3ß phosphorylation and ß-catenin activation (p < 0.05 for all measurements). Additionally, EZH2 knockdown sensitized AML cells to induced cell death following administration of chemotherapeutic ATO. Our results suggested that EZH2 in leukemic cell lines might inhibit ATO-induced apoptosis and that EZH2 may be a potential therapeutic target in AML patients undergoing ATO treatment. Our findings provide new insights into the role of ATO and EZH2 in regulating AML progression.

Galectin-3 as a marker and potential therapeutic target in breast cancer.

Galectin-3 has a relatively high level of expression in triple-negative breast cancers and is a potential marker for this disease. However, the clinical and prognostic implications of galectin-3 expression in breast cancer remain unclear. We examined mastectomy specimens from 1086 breast cancer cases and matching, adjacent non-cancerous tissues using immunohistochemistry. Overall, triple-negative breast cancers expressed galectin-3 more strongly than did other breast cancers types (63.59% vs 21.36%, P = 0.001). Galectin-3 expression was not found to be an independent prognostic factor for breast cancer by Cox regression analysis, but was associated with chemotherapeutic resistance. Apoptosis was only weakly induced by arsenic trioxide (ATO) treatment in galectin-3-positive breast cancer cells (MDA-MB-231 and MCF-7), although ATO treatment up-regulated galectin-3 expression. Knockdown of galectin-3 in MDA-MB-231 cells sensitized them to killing by ATO. These findings support a possible role for galectin-3 as a marker for triple-negative breast cancer progression and as a therapeutic target in combination with ATO treatment, although the mechanisms that underlie this synergy require further investigation.

Gross total resection of glioma with the intraoperative fluorescence-guidance of fluorescein sodium.

OBJECTIVE: High dose fluorescein sodium has been utilized for fluorescence-guided tumor resection with conflicting reports on the efficacy of this procedure. The aim of this study was to reevaluate the utility and clinical limitations of using fluorescein sodium for the treatment and resection of glioma brain tumors. METHODS: Patients diagnosed with glioma were divided into two groups with a total of 22 patients enrolled in the study: 1) the study group (n=10), patients that received intravenous injection of fluorescein sodium and 2) the control group (n=12), patients that did not receive injections during surgical resection. Quality of life was evaluated according to Karnofsky Performance Scale (KPS) score and neurological status. Fluorescein sodium was intravenously injected at a dose of 15-20mg/kg of body weight. Glioma resection was evaluated preoperative and postoperatively with enhanced Magnetic Resonance Imaging (MRI). RESULTS: Significant differences in the gross total resection (GTR) rates were observed between the two patient groups (Fisher's Exact Test p=0.047). Progressive free survival was significantly longer in the study group (Student's T-Test p=0.033) as well as in the GTR group (Student's T-Test p=0.0001) compared to the control and non-GTR groups, respectively. Three patients in the study group and four patients in the control group had transient neurological deterioration. One patient in the control group had permanent hemiplegia. CONCLUSION: The intraoperative utility of using fluorescein sodium can significantly increase the GTR rate without obvious deterioration. In addition, we find that it is better to apply the fluorescein sodium in the cases with BBB (blood-brain barrier) disruption, which had been enhanced in preoperative MRI.