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The objective of this study was to examine the expression and significance of β-catenin in the diagnosis and prognosis of breast cancer. Overall, 241 patients with histologically confirmed breast cancer who had undergone radical surgery were enrolled in this study. β-catenin protein expression in breast cancer samples was evaluated by immunohistochemistry. β-catenin was expressed in Nuclei/Plasma of the samples from 41 patients. β-catenin protein expression correlated with the histological grade of the tumor (P<0.05) and Ki-67 labeling (P<0.01). Survival analysis showed that β-catenin expression negatively correlated with breast cancer-specific survival. Our results showed prominent expression of β-catenin in breast cancer and strongly implicate the β-catenin in tumor promotion.

Objective: To investigate the effect of elemene on the radiosensitivity of A549 cells and its possible molecular mechanism., Methods: Apoptosis of A549 cells was detected by flow cytometry and fluorescence microscopy. The effect of double-strand break (DSB) damage repair in A549 cells was evaluated using the neutral comet assay. Protein expression levels were detected using western blotting, and the correlation between protein levels was analyzed., Results: Elemene exhibited a radiosensitizing effect on A549 cells. The level of apoptosis induced by elemene combined with radiation was significantly greater (p<0.01) than that elicited by either radiation or elemene alone. Following radiation and subsequent repair for 24 h, the tail intensity of A549 cells treated with a combination of elemene and radiation was greater than that of cells treated with either elemene or radiation alone (p<0.01). This result indicates that elemene inhibits cellular DSB repair. Both elemene combined with radiation and radiation alone decreased the protein expression of DNA-PKcs and Bcl-2 compared to elemene alone (p<0.01), while p53 protein expression was increased (p<0.01). A negative correlation was observed between DNA-PKcs and p53 expression (r=-0.569, p=0.040), while a positive correlation was found between DNA-PKcs and Bcl-2 expression (r=0.755, p=0.012)., Conclusions: Elemene exhibits a radiosensitizing effect on A549 cells, and its underlying molecular mechanism of action may be related to the downregulation of DNA-PKcs gene expression.

Small proline-rich repeat protein 1A (SPRR1A) is a marker for terminal squamous cell differentiation. Previous studies showed that SPRR1A expression increases in squamous cell carcinoma of the skin, but decreases in esophageal squamous cell carcinoma. This study focuses on the expression of SPRR1A protein in breast cancers (BCs) in China. A total of 111 patients with histologically confirmed BC, who underwent radical surgery between January 2006 and September 2007 in China Medical University, were enrolled. The relationship between SPRR1A expression and clinicopathological factors as well as BC prognoses was also determined. Overall, SPRR1A expression was detected in more than half of the BC specimens by immunohistochemistry (56/111, 53.8%), but there was no significant difference between age groups (≥50 vs. <50 years) in terms of SPRR1A expression (P = 0.915), as well as no differences between SPRR1A expression and the clinical stage (0-I vs. II-III) or nodal status (P = 0.234 and 0.632, respectively). Moreover, human epidermal growth factor receptor 2 overexpression was not correlated with SPRR1A expression, whereas Ki67 was associated with SPRR1A expression (P = 0.155 and 0.028, respectively). Interestingly, SPRR1A expression was significantly associated with progesterone receptor-positive (P = 0.010) rather than estrogen receptor-positive (0.778) BCs. The 5-year survival rate in patients did not differ with the presence or absence of SPRR1A expression (P = 0.753), whereas the combination of SPRR1A expression, progesterone receptor status, and menopausal status allowed identification of a subgroup of BC patients with a good long-term prognosis. Thus, the SPRR1A status might play an important role in the prognosis of postmenopausal breast carcinoma patients, especially that of progesterone receptor-positive subgroups.

WT1 + KTS and -KTS isoforms only differ in 3 amino acids in protein sequence but show significant functional difference. The +/-KTS isoforms were generated by alternative usage of 2 adjacent 5' splice sites at RNA level, however, how these 2 isoforms are regulated is still elusive. Here we report the identification of an intronic pyrimidine-rich sequence that is critical for the ratio of +/-KTS isoforms, deletion or partial replacement of the sequence led to full/significant shift to -KTS isoform. To identify trans-factors that can regulate +/-KTS isoforms via the binding to the element, we performed RNP assembly using in vitro transcribed RNA with or without the pyrimidine-rich sequence. Mass spectrometry analysis of purified RNPs showed that the element associated with many splicing factors. Co-transfection of these factors with WT1 reporter revealed that HuR promoted the production of -KTS isoform at the reporter level. RNA immuno-precipitation experiment indicated that HuR interacted with the pyrimidine-rich element in WT1 intron 9. We further presented evidence that transient or stable over-expression of HuR led to enhanced expression of endogenous -KTS isoform. Moreover, knockdown of HuR resulted in decreased expression of endogenous -KTS isoform in 293T, SW620, SNU-387 and AGS cell lines. Together, these data indicate that HuR binds to the pyrimidine-rich sequence and antagonize its effect in regulating WT1 +/-KTS isoforms.

The aim of this study is to explore the expression of BAF250a protein in breast cancer and its association with the clinical and pathological characteristics and prognosis of breast cancer. The expression status of BAF250a protein was detected by Western blot analysis and immunohistochemical staining. The relationship between BAF250a proteins and clinicopathological parameters in 496 breast cancer specimens was analyzed. Western blot analysis showed that BAF250a protein had a lower expression in breast cancer specimens than in matched normal breast tissue (104.38 ± 11.65 vs. 55.94 ± 10.27; P = 0.004, t test). Among the 496 enrolled breast cancer patients, BAF250a protein expression was absent in 324 (65.3 %). Universal and multiple analyses indicated that BAF250a protein expression loss was significantly related to histological grade, metastatic nodes, tumor node metastasis (TNM) stage, and the expression of estrogen receptor (ER), progesterone receptor (PR), c-erbB-2, and p53 (all P < 0.05). For TNM stage, rank correlation coefficients were 0.199 and 0.191, respectively, (P < 0.05), but BAF250a protein deletion had either a positive or a negative correlation with ER, PR, c-erbB-2, and p53 protein expression (correlation coefficients were 0.231, 0.207, -0.098, -0.128; P < 0.05). Analysis of survival rates showed that the patients with BAF250a protein expression attained a significantly better postoperative disease-specific survival than those with BAF250a protein deletion (88.4 vs. 79.0%; P = 0.003). In the Cox regression test, BAF250a protein deletion was detected as an independent prognostic factor (P = 0.014). BAF250a protein might be a new potential target for breast cancer treatment.

The purpose of this study is to investigate the relationship between nestin expression and clinicopathological characteristics, immunohistochemical markers and to determine the prognostic impact of nestin expression in breast cancer so as to lay a foundation for the treatment of breast cancer. A total of 109 patients who were histologically diagnosed with breast cancer and underwent radical operations from January 2006 to September 2007 in China Medical University were enrolled in the study. Nestin protein expression was evaluated by immunohistochemistry. The relationship between nestin and other parameters was analyzed by using chi-square test and Fisher's exact test. Nestin expression was observed in 37.6% (41/109) of cases. There were no significant differences between the age of >40 and ≤40 years group in terms of nestin expression (39.8 vs 18.2%; P = 0.161). The rate of nestin expression between those with and without lymph node metastasis was not significantly different (X (2) = 0.086; P = 0.769). The 5-year survival rates of the patients with nestin expression and those without were 34.1% (14/41) and 55.9% (38/68), respectively (P = 0.028). Overall, triple-negative breast cancers had higher expression rates than other cancers (54.1 vs 29.2%; P = 0.011). Nestin expression rate in ER- and PR-negative tumors was found to be significantly higher than cases that were ER- and PR-positive (P = 0.011 and P = 0.036, respectively). However, it was not found that HER2 expression was related to nestin expression (P = 0.120). These results suggest that the expression of nestin might play an important role in the prognosis of breast carcinoma, especially in the triple-negative subgroups.

It is well-established that triple-negative breast cancer (TNBC) is a subtype of breast cancer, characterized by a poor prognosis and aggressive biological behavior. However, the available relevant data on TNBC in non-Western populations are limited. In order to analyze the clinicopathological and molecular biological characteristics and observe survival and prognostic factors, 972 breast cancer patients (156 of whom had TNBC) who received treatment at the First Affiliated Hospital of Medical School of Xi'an Jiaotong University and the First Hospital of China Medical University, between January, 2004 and January, 2007 were retrospectively evaluated. In the univariate analysis, tumor size, TNM stage, axillary lymph node status and recurrence or metastasis were identified as prognostic factors for 7-year disease-free survival (DFS) and overall survival (OS). Our multivariate Cox's regression analysis demonstrated that tumor size and axillary lymph node status were significant prognostic factors for 7-year DFS and OS. Notably, tumor subgroup (TNBC vs. non-TNBC) was a significant prognostic factor associated with 7-year DFS and OS in breast cancer. It was suggested that TNBC exhibited a worse 7-year survival compared with that in non-TNBC patients, most likely due to its more aggressive behavior and insensitivity to specific therapy.

The objective of this study was to investigate the expression and significance of the GRHL3 protein in breast cancer diagnosis and prognosis. Overall, 111 patients with histologically confirmed breast cancer who had undergone radical surgery were enrolled in this study. The GRHL3 protein expression status in the breast cancers was evaluated by immunohistochemistry. The relationship between GRHL3 protein expression status and clinicopathological factors and the breast cancer prognoses was also determined. In total, 71 (63.96%) out of 111 cases were found to express GRHL3 protein. GRHL3 expression was higher in breast cancers, compared to other pathologic cancer types (χ (2) = 5.68, P < 0.05). Moreover, GRHL3 protein was also observed to correlate with breast cancer clinical stage and histological grade (χ (2) = 7.99, P < 0.05 and χ (2) = 7.907, P < 0.05, respectively). Interestingly, triple-negative breast cancers had lower expression rates than other breast cancers (41.18 vs. 71.28%, P < 0.05). GRHL3 was shown to be an independent prognostic factor of breast cancer in Cox regression analysis. Altogether, our results indicate predominant GRHL3 expression in breast cancers, especially non-triple-negative cancers and early stage cancers. GRHL3 expression appeared to decrease with tumor progression. Survival analysis demonstrated the inhibitory effect of GRHL3 in breast cancer. These results strongly suggest the possible involvement of GRHL3 in tumor suppression.

In this study, we try to detect and isolate the cancer stem cell-like side population cells (SP) from the laryngeal carcinoma cell line and primary laryngeal carcinoma and explore the clinical implications of SP cells in laryngeal carcinoma. The SP cells and non-side population cells (NSP) cells were sorted by Hoechst 33342 through FACS. The proliferation capacity, invasion ability, migration ability, and tumorigenic activity of the SP cells were evaluated. In addition, the association between the SP cells ratio and the prognostic factors of laryngeal cancer was analyzed. As a result, the percentage of the SP cells in Hep-2 cells was 5.1%. The SP cells depicted float colonies, but the NSP cells failed to generate the typical cell spheres. The clone formation ratios were 47.47 ± 10.20% vs. 4.98 ± 1.41% in the flat plates and 46.82 ± 5.67% vs. 12.53 ± 3.51% in the soft agar for SP and NSP cells (P = 0.01 and 0.01). The SP cells depicted a higher migrating potency than the NSP cells in both the transwell assay and scarification test (all P < 0.05). The matrigel invasion assay showed that the artificial basement membrane penetration rate of SP cells was 39.04 ± 4.78%, which was higher than 25.16 ± 4.63% of the NSP cells (P < 0.05). Only 10(3) SP cells were able to form tumors in mice, whereas 10(4) NSP cells failed to form tumors. The SP cells were correlated with the differentiation, lymph node metastasis, and clinical stage of the laryngeal cancers. In conclusion, SP cells may be a potential prognostic factor of laryngeal cancer.

Background: To investigate the expression status of PIWIL2 and piR-932 in breast cancer stem cells and the role they could play in tumor cell growth and metastasis through Latexin., Methods: CD44(+)/CD24(-) tumor cells (CSC) from clinical specimens were sorted using flow cytometry. PIWIL2 expression status was detected in CSC cells by microarray analysis and 1086 breast cancer specimens by Western blot and immunohistochemistry staining. piR-932 expression was also detected in CSC cells by piRNA microarray assay. The relationship between the PIWIL2 protein and clinico-pathological parameters and prognosis was subsequently determined., Results: CSC cells are more likely to generate new tumors in mice and cell microspheres that are deficient in NOD/SCID compared to the control group. PIWIL2 protein was expressed higher in CSC cells compared to the control cells. In total, 334 (30.76%) of the 1086 breast cases showed high PIWIL2 expression. PIWIL2 was observed to be related to age, tumor size, histological type, tumor stage, and lymph node metastasis (all P < 0.05). Furthermore, we have found that one of the Piwi-interacting RNAs (piRNAs) called piR-932 expressed significantly higher in the breast cancer cells that were induced to EMT, and it could form immune complexes through immunoprecipitation with PIWIL2; in PIWIL2+ breast cancer stem cells, Latexin expression significantly reduced because of its promoter region CpG island methylation., Conclusions: These results suggest that the combination of piR-932 and PIWIL2 may be a positive regulator in the process of breast cancer stem cells through promoting the methylation of Latexin, and they both could be the potential targets for blocking the metastasis of breast cancer., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Twenty five percent of women with breast cancer who undergo preoperative chemotherapy do not have axillary metastases. These patients need to withstand sentinel lymph node biopsy (SLNB). The optimal timing of SLNB in patients with neoadjuvant chemotherapy has not yet been defined., Methods: We systematically reviewed the literature for studies concerning the efficacy of sentinel lymph node biopsy before neoadjeuvant chemotherapy. A literature search was performed for the years 1993 through 2011 using the databases MEDLINE and EMBASE. Data that assessed the reliability of sentinel lymph node biopsy before chemotherapy were collected., Results: We identified 10 high-quality studies from 387 papers, which are analyzed further in this review. The identification rates reported ranged from 97% to 100%. The sensitivities of sentinel lymph node biopsy were 100%, and the false negative rates were 0%. Use an isotope combined with blue dye was associated with a higher probability of identification than that of using an isotope or blue dye alone (99.5% vs 98.5%). Only two studies compared data based on different timing for the sentinel lymph node biopsy. They achieved a lower false negative rate (0% vs 15.8%) and higher success rate (100% vs 81%) in patients with sentinel lymph node biopsy prior to neoadjuvant chemotherapy., Conclusion: Sentinel lymph node biopsy prior to chemotherapy potentially gives a more accurate evaluation of axillary status, because it is unaffected by any previous therapeutic intervention., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objectives: To evaluate the medium-term outcomes of using tension-free vaginal tape-obturator (TVT-O) in the treatment of patients with stress urinary incontinence (SUI)., Study Design: Between December 2004 and November 2005, 103 patients with SUI were enroled and treated with TVT-O with inside-out modification. A minimum five-year follow-up (median, 65 months) was obtained from 100 patients (99.6%). Preoperative and postoperative evaluations were performed for all patients. The objective success rate of the TVT-O procedure was evaluated by a negative stress test. The secondary outcomes measured included one- and five-year subjective success rates, together with the pre- and post-operative urodynamic parameters, complications, quality of life (QOL) analysis, and patient satisfaction., Results: Among the 103 patients, 18 (17.4%) had postoperative voiding difficulties and needed urethral bladder catheterization for various periods. After the TVT-O procedure, complete disappearance of SUI occurred in 87.4% of patients, while improvement was found in about 92%. In addition, there was no difference in the cure rate between year 1 and year 5 after the procedure (P>0.05). In 90 patients, frequency and urge symptoms were significantly improved five years after the procedure (P<0.005), and maximal flow rates were decreased (P<0.05). However, the severity of obstructive symptoms and postvoid residual volumes at five years were not improved compared with one year after the procedure (P=0.10 and P=0.33 respectively). Finally, compared to pre-operation, incontinence severity degree and QOL scale scores were largely improved after the operation (P<0.001), while no difference was found between years 1 and 5 (P=0.11and P=0.09 respectively)., Conclusions: Our result shows that the TVT-obturator, a novel mid-urethral sling, is a safe and effective procedure for the treatment of female SUI. Medium-term therapeutic results appear promising but further evaluation of long-term therapeutic outcomes is needed., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Dioctophyma renale is a parasite that frequently occurs in animals but rarely in humans. The present report describes the clinical observations of a D. renale infection in a 51-yr-old woman. Its clinical signs and diagnostic findings were unspecific until giant worms were observed in the urine and histological findings confirmed it was a D. renale infection. She refused treatment and died of bilateral renal function failure. This is the first confirmed report to follow the natural progression of D. renale infection in a human. Here, we discuss a conservative therapeutic approach and features associated with this parasitic infection.

Background: For intramucosal undifferentiated early gastric cancer (EGC), gastrectomy with lymphadenectomy is now the standard therapy. However, because approximately 96% of intramucosal undifferentiated EGC do not have lymph node metastasis (LNM). Gastrectomy with lymphadenectomy may be overtreatment for such patients. This study was conducted to identify clinicopathological factors predictive of LNM in undifferentiated EGC and further to expand the possibility of using endoscopic mucosal resection (EMR) for the treatment of undifferentiated EGC., Methods: Data from 108 patients with undifferentiated EGC and surgically treated were collected, and the association between the clinicopathological factors and the presence of LNM were retrospectively analyzed by univariate and multivariate logistic regression analyses. Odds ratios (ORs) with 95% confidence interval (95% CI) were calculated., Results: The tumor size (OR=11.475, 95% CI: 2.054-64.104, P=0.005), depth of invasion (OR=11.704, 95% CI: 2.536-54.010, P=0.002), and lymphatic vessel involvement (LVI) (OR=13.688, 95% CI: 1.779-105.324, P=0.012) that were significantly associated with LNM by univariate analysis, were found to be significant and independent risk factors for LNM by multivariate analysis. The LNM rates were 5% (3/61) and 28% (13/47) with intramucosal and submucosal undifferentiated EGC respectively. LNM was observed in 50% (1/2) of patients with both risk factors (tumor larger than 2.0cm and the presence of LVI) but in none of 25 patients without the two risk factors in intramucosal undifferentiated EGC. The 5-year survival rates were 88%, 82% and 50%, respectively in cases with none, one and two of the risk factors respectively in intramucosal undifferentiated EGC (P<0.05)., Conclusions: A tumor larger than 2.0cm, submucosal invasion, and the presence of LVI are independently associated with the presence of LNM in undifferentiated EGC. EMR alone may be sufficient treatment for intramucosal undifferentiated EGC if the tumor is less than or equal to 2cm in size, and when LVI is absent upon postoperative histological examination. When specimens show with LVI, unexpected submucosal invasion, and unexpectedly larger tumor size than that determined at pre-EMR endoscopic diagnosis, an additional radical gastrectomy is probably better for these patients., (Copyright © 2010. Published by Elsevier Ltd.)

Background: Lymphatic vessel invasion is an important prognostic factor for the gastric cancer without lymph node metastasis. However, the studies on early gastric cancers is still sparse. Therefore, we carried out this study to determine clinicopathological and surgical prognostic factors, especially lymphatic vessel invasion, for early gastric cancers., Methods: Clinicopathological characteristics and prognostic outcomes of 188 patients who received a gastrectomy for early gastric cancer between 1980 and 2000 were retrospectively evaluated based on the subclassification of pN category. A multivariate analysis was performed by using the Cox regression model, where lymphatic vessel invasion and other potential prognostic factors were included., Results: Of the 188 patients, 158 had T1N0M0 and 30 T1N1M0 cancers. In patients with T1N0M0 cancers, the survival rate was significantly lower in those with lymphatic vessel invasion than in those without (chi(2)=4.025, P=0.045). However, in patients with T1N1M0 cancers, the survival rates were not significantly different between those with and those without lymphatic vessel invasion (chi(2)=0.253, P=0.615). The multivariate analysis identified that age (P=0.033) and lymph node metastasis (P=0.019) were independent prognostic factors for all early gastric cancers. However, age (P=0.042), tumor location (P=0.032), and lymphatic vessel invasion (P=0.010) were the independent prognostic factors for T1N0M0 cancers., Conclusions: Lymphatic vessel invasion was an independent prognostic factor for T1N0M0 early gastric cancers, and thus may be a potential prominent factor that should be considered to be included in the category of lymphoid metastasis (both lymph node metastasis and lymphatic vessel invasion) in patients with early gastric cancer., (Copyright 2008 Elsevier Ltd. All rights reserved.)

Purpose: To investigate the impact of total retrieved lymph nodes (tLNs) on staging and survival in patients with pT2b gastric cancer according to the nodal status., Methods: Clinicopathological characteristics and prognostic outcomes of 392 patients with pT2b gastric cancer between 1980 and 2005 were retrospectively investigated based on the nodal status., Results: The number of metastatic lymph nodes (mLNs) was highly correlated with the number of tLNs (P<0.001). The overall 5-year and 10-year survival rates were 39.0% (153/392) and 17.9% (70/392), respectively. The survival rates in patients with pN0 cancers did not differ significantly from that in patients with pN1 cancer when the tLNs were 25 or less. However, the survival rate in patients with N0 cancers was significantly greater than that in patients with pN1 cancers when the tLNs were more than 25 (64.3% vs. 36.9%, chi(2)=4.339, P=0.037). Moreover, both 5- and 10-year survival rates differed significantly among patients with pN1, pN2 and pN3 gastric cancer regardless of tLNs. Multivariate analysis revealed that age, tumor focus number, tumor location, and mLN, but not tLNs, were independent prognostic predictors in patients with pT2b gastric cancer., Conclusions: To improve the accuracy of staging, no less than 15 tLNs should be pathologically examined in patients with pN1-3, and 25 tLNs for the patients with N0. More tLNs may not be associated with a better prognosis in pT2b disease because the extent of lymph node dissection is pre-defined for the operation.