Low expression of PDHA1 predicts poor prognosis in gastric cancer

PDH E1 component subunit alpha (PDHA1) has been reported to be biologically significant in several human tumors. The aim of this study was to investigate the expression of PDHA1 in gastric cancer (GC) and its relationship with clinicopathological characteristics and prognosis. Oncomine analysis of neoplastic vs. normal tissue showed that the mRNA levels of PDHA1 were significantly underexpressed in different types of GC across three analyses. Underexpression of PDHA1 was found in intestinal-type GC (P?=? 0.009), diffuse-type GC (P?=? 0.036), and mixed-type GC (P?=? 0.025). Immunohistochemical staining of the 174 GC tissue microarray showed that PDHA1 staining is much stronger in normal mucosa than in GC samples (P?=? 0.040). Furthermore, PDHA1 expression levels were found to be significantly lower in 69.05% (87/126) of poorly differentiated GCs as compared to the well or moderately differentiated ones (P?=? 0.037). Intriguingly, PDHA1 expression was significantly correlated with depth of invasion (P?<? 0.001), lymph node metastasis (P?<? 0.001), TNM stage (P?<? 0.001), and nerve invasion (P?=? 0.006). However, it was not correlated with gender, age, Lauren classification, and lymphovascular invasion (P > 0.05 for all). Kaplan-Meier analysis revealed that low tumor expression of PDHA1 was significantly correlated with a poorer overall survival in patients with GC (5-year overall survival rates for patients with low vs high PDHA1 expression?=?49.8% vs 72.7%, hazard ratio of death from GC?=?2.594, 95% CI?=?1.527 to 4.408, P?<? 0.001). Multivariate analysis showed that PDHA1 (P?=? 0.025) was an independent predictor of overall survival. These findings are of potential clinical utility and merit further validation.     

High expression of spindle assembly checkpoint proteins CDC20 and MAD2 is associated with poor prognosis in urothelial bladder cancer

Aneuploidy is a result of the abnormal expression of spindle assembly checkpoint (SAC) proteins and resulting abnormal spindle function during mitosis. High expression of cell division cycle 20 homolog (CDC20) and mitotic arrest defective protein 2 (MAD2), key components of the SAC, has been reported in various carcinomas. However, the clinicopathological significance of CDC20 and MAD2 expressions in urothelial carcinoma of the human bladder (UCB) is unknown. We therefore studied the expression of CDC20 and MAD2 in UCB specimens by immunohistochemistry. High expression of CDC20 and MAD2 was observed in 59.0 % (200/339) and 51.0 % (173/339) of UCB cases, respectively. Most high-grade tumor cells exhibited diffuse nuclear and/or cytoplasmic staining for CDC20 and MAD2, whereas most low-grade tumor cells and normal urothelial cells were not stained. CDC20 overexpression was associated with advanced age (p?=?0.010), high grade (p?<?0.001), advanced stage (p?<?0.001), non-papillary growth pattern (p?<?0.001), and distant metastasis (p?=?0.042). Similarly, high MAD2 expression correlated with high grade (p?<?0.001), advanced stage (p?<?0.001), and non-papillary growth pattern (p?<?0.001). In univariate survival analyses, high CDC20 expression correlated with shorter recurrence-free survival (RFS) (p?=?0.032) and poorer overall survival (OS) (p?=?0.007) in patients with UCB, whereas high MAD2 expression was associated with poorer OS (p?=?0.008). In multivariate analyses, high CDC20 expression correlated with shorter RFS of patients with Ta stage UCB (hazard ratio, 1.91; p?=?0.01). In conclusion, increased expression of CDC20 and MAD2 is related to poor prognosis of UCB.     

Survivin expression is an independent poor prognostic marker in lung adenocarcinoma but not in squamous cell carcinoma

Survivin is a member of the inhibitors of apoptosis and frequently overexpressed in various cancer cells. Overexpression of survivin in lung cancer cells attenuates antitumor effect of tyrosine kinase inhibitors. However, data from the previous studies on the clinicopathologic implication of survivin in non-small-cell lung carcinoma (NSCLC) are inconsistent. We investigated the expression of survivin in 373 cases of surgically resected NSCLC. Correlations between the expression of survivin and clinicopathologic, molecular features and prognostic significance were analyzed. In adenocarcinoma, the increased expression of survivin was associated with the presence of vascular invasion, lymph node metastasis, and tumor recurrences, but we didn’t find any correlation with survivin expression and clinicopathological parameters in squamous cell carcinoma. Patients with high survivin expression had significantly shorter disease-free survival (DFS; 42.2 vs. 58.8 months; p?=?0.001) and shorter overall survival (OS; 60.8 vs. 71.5 months; p?=?0.009) than those with low survivin expression group in adenocarcinoma. In squamous cell carcinoma, the expression of survivin was not associated with prognosis of the patients (DFS; 48.9 vs. 48.7 months; p?=?0.837, OS; 61.0 vs. 62.4 months; p?=?0.771). Multivariate analysis confirmed that survivin was an independent poor prognostic factor in adenocarcinoma (DFS: hazard ratio (HR), 1.687; 95 % confidence interval (CI), 1.123–2.532; p?=?0.012; OS: HR, 1.965; 95 % CI, 1.108–3.486; p?=?0.021). There was no statistically significant difference in the expression of survivin among different molecular subgroups (p?>?0.05). Our results suggest that survivin is an independent negative prognostic factor in adenocarcinoma, but not in squamous cell carcinoma. The different prognostic roles played by survivin in adenocarcinoma and squamous cell carcinoma highlights the biological differences between these two histologic types.     

Aberrations of MET are associated with copy number gain of EGFR and loss of PTEN and predict poor outcome in patients with salivary gland cancer

Hepatocyte growth factor receptor (MET) is a key driver of oncogenic transformation. Copy number gain and amplification of MET positively enhance tumour growth, invasiveness and metastasis in different cancer types. In the present study, 266 carcinomas of the major and minor salivary glands were investigated for genomic MET status by fluorescence in situ hybridization and for protein expression by immunohistochemistry. Results were matched with clinicopathological parameters, long-term survival and the status of epidermal growth factor receptor (EGFR) and phosphatase and tensin homologue (PTEN). Low polysomy (n?=?42), high polysomy (n?=?27), amplification (n?=?2) and deletion (n?=?18) were found as aberrations of genomic MET in certain subtypes. MET aberrations were associated with increased patient age (>70 years, p?=?0.003), male gender (p?=?0.01), increased tumour size (p?=?0.002), lymph node metastases (p?<?0.001), high-grade malignancy (p?<?0.001) and unfavourable overall survival (p?<?0.001). Both copy number gain (p?<?0.001) and deletion (p?=?0.031) of MET correlated with copy number gain of EGFR. Tumours with genomic loss of PTEN (n?=?48) concurrently presented aberration of genomic MET (p?<?0.001). MET gene status significantly correlated with protein status (p?=?0.038). In conclusion, gain but also loss of genomic MET activity correlates with aggressive tumour growth, nodal metastasis and worse overall survival in salivary gland cancer. Moreover, aberrations of MET are associated with EGFR and PTEN signalling and might possess relevance for targeted therapies of salivary gland carcinomas in the future.     

Co-expression of receptors of the HER family correlates with clinical outcome in non-small cell lung cancer (NSCLC)

HER family receptors play a critical role in lung carcinogenesis. There is a growing body of evidence showing that cooperation between them contributes to a more aggressive tumor phenotype and impacts on their response to targeted therapy. We explored immunohistochemical co-expression of HER family receptors (HER1, HER2, HER3, HER4) and its potential role as prognostic factor in resected non-small cell lung cancer (NSCLC). Expression of HER family receptors was assessed by immunohistochemistry on 125 surgically resected NSCLC. Kaplan–Meier estimates of overall survival (OS), disease-free survival (DFS), and time to recurrence were calculated for clinical variables and HER expression, using the Cox model for multivariate analysis. HER1 and HER3 expression was detected more frequently in squamous cell carcinoma (p?=?0.002 and p?=?<0.001, respectively). HER4 was more often expressed in patients older than 60 years (p?=?0.02) and in tumors of low histological grade (p?=?0.04). Cases which expressed only HER1 had a worse DFS (p?=?0.01) and OS (p?=?0.01) compared to cases expressing HER1 and one or more of the other family members and to cases which did not express HER1 but one of the other HERs. By multivariate analysis, stage was an independent prognostic factor for DFS and OS. Furthermore, different patterns of co-expression of HER family receptors showed a statistically significant correlation with a shorter DFS (p?=?0.03) and OS (p?=?0.02). Our findings suggest that expression of HER1 only is correlated with worse DFS and OS. A better understanding of the functional relationships between these receptors may lead to a useful predictive indicator of response to targeted therapy.     

Overexpression of matriptase correlates with poor prognosis in esophageal squamous cell carcinoma

Matriptase is one of the type II transmembrane serine proteases and is known to be involved in cancer progression. Increased matriptase expression has been reported in a variety of human cancers, and its association with poor prognosis has been highlighted in some cancer types. However, its exact role in cancer progression and its effect on patient survival in esophageal squamous cell carcinoma (ESCC) are still unclear. We performed immunohistochemical staining of matriptase in 171 ESCC samples after antibody validation and evaluated the association of its expression with clinicopathological parameters and prognosis. High matriptase expression was observed in 38.6 % (66/171) of ESCC samples and more frequently in N3 stage and in poorly differentiated tumors. Both overall survival (OS) and disease-free survival (DFS) were significantly lower for patients with high expression of matriptase than for patients with low expression (5-year OS rate, 38.6 vs 55.3 %; p?=?0.034 and 5-year DFS rate, 30.5 vs 49.4 %; p?=?0.007). High matriptase expression was an independent prognostic factor for OS [hazard ratio (HR), 1.65 (95 % confidence interval (CI), 1.01–2.68); p?=?0.045] and for DFS [HR, 1.79 (95 % CI, 1.14–2.81); p?=?0.012]. In conclusion, higher expression of matriptase is an independent prognostic factor involved in the progression of ESCC, which suggests that matriptase is a factor in ESCC tumor progression and also a potential molecular therapeutic target.     

Impact of Environmental Factors on Efficacy of Glucocorticoids in Chinese Population with Systemic Lupus Erythematosus

Although glucocorticoids (GCs) are effective in inducing remission in systemic lupus erythematosus (SLE) patients, there is a significant variation in response to therapeutic GCs, and some patients do not achieve full remission. The aim of this study was to explore the impact of environmental factors on the efficacy of GCs in a Chinese population with SLE. This was a prospective cohort study, and a total of 260 SLE patients treated with GCs (prednisone) were followed up for 12 weeks. The efficacy of GCs was measured with the scores on SLE disease activity index. Environmental factors were collected using a questionnaire. Single-variable analysis and multivariate logistic regression analysis were used to discriminate the impact of environmental factors on the efficacy of GCs. Two hundred forty-seven patients (95.00 %) completed the 12-week follow-up. Among these patients, 131 (53.04 %) were classified into sensitive group and 116 (46.96 %) were classified into insensitive group. Results from logistic analysis showed that the following environmental factors were significantly associated with decreased efficacy of GCs: high salt intake (OR?=?3.464, 95%CI?=?1.481–8.102, P?=?0.004), introverted personality (OR?=?3.550, 95%CI?=?1.901–6.628, P?<?0.0001), experience with negative life events (OR?=?5.526, 95%CI?=?1.612–18.946, P?=?0.007), and history of allergy (OR?=?2.966, 95%CI?=?1.312–6.704, P?=?0.009). These results indicate that environmental factors, including salt intake, personality, experience with negative life events, and history of allergy, may play an important role in the efficacy of GCs in the Chinese population with SLE.     

Ribotype 027 Clostridium difficile infections with measurable stool toxin have increased lactoferrin and are associated with a higher mortality

We evaluated clinical and diagnostic indicators of severe C. difficile infection (CDI) and their association with poor clinical outcome. A total of 210 patients positive according to PCR (toxin B: tcdB) were included, with patients having a median age of 62 years and a Charlson co-morbidity index (CI) score of 5. Ninety-one percent (n?=?191) were positive by toxigenic culture and 61 % (n?=?129) had stool toxin. Toxin-positive patients had significantly higher fecal lactoferrin (mean 316 μg/g versus 106 μg/g stool; p?<?0.0001). Forty percent of patients (n?=?85) were infected with ribotype 027 and significantly more of these patients had measurable stool toxin (79 % vs. 50 %; p?<?0.0001). The mean fecal lactoferrin was significantly higher for toxin-positive 027 CDI compared with the 027 toxin-negative group (317 vs 60 μg/g; p?=?0.0014). Ribotype 027 CDI with stool toxin showed a higher all-cause, 100-day mortality compared with non-027 with stool toxin (36 % vs 18 %; p?=?0.017). Logistic regression univariate analysis for odds ratio (OR) and p values revealed that age (OR?=?1.1), intensive care unit treatment (OR?=?2.7), CI (OR?=?1.2), 027 CDI (OR?=?2.1), white blood cell count (OR?=?1.0), albumin level (OR?=?0.1), and stool toxin-positive 027 CDI (OR?=?2.5) were significantly associated with 100-day mortality (p?<?0.05). In conclusion, CDI PCR-positive patients with 027 infection and stool toxin have increased lactoferrin and are at an increased risk of death.     

Selenium and lipid subfractions in Egyptian type 2 diabetes patients

The purpose of this study was to examine the relationship between serum selenium (Se) levels and lipid subfraction among Egyptian type 2 diabetes patients and their association with the severity of the disease. The study was conducted on 60 type 2 diabetic adults with BMI <30 divided according to disease duration into two groups: group 1 with disease duration less than 5 years and group 2 with a disease duration more than 5 years. Thirty age- and sex-matched apparently healthy volunteers were considered as the control group. Serum selenium was measured by atomic absorption spectrometry lipid subfractions including small dense low density lipoprotein (sd LDL) which was measured by enzyme-linked immunosorbent assay and glycated hemoglobin (HbA1c) by high-performance liquid chromatography. All participants do not receive Se supplementation. The mean serum Se level in participants with diabetes was as follows: group 2?=?62.70?±?5.73, group 1?=?70.58?±?4.158, and control subjects?=?79.80?±?5.37 μg/l (p?=?0.00). Se was found to be an independent protective factor with an OR of 0.29 and 95 % CI of 0.06–1.3. Mean serum sd LDL in participants with diabetes was as follows: group 2?=?43.81?±?13.70, group 1?=?25.77?±?5.28, and control group?=?15.99?±?5.32 (p?=?0.00). Correlation study, between studied parameters, revealed positive correlation between sd LDL and apolipoprotein B (Apo B) (r?=?0.730, p?=?0.001). On the other hand, negative correlation was encountered between apolipoprotein A (Apo A) and Apo B (r?=??0.514, p?=?0.001) as well as Apo A and sd LDL (r?=??0.697, p?=?0.001). Selenium correlated negatively with both Apo B (r?=??0.669, p?=?0.001) and sd LDL (r?=??0.671, p?=?0.001) and positively with Apo A (r?=?0.513, p?=?0.001). In a sample of the Egyptian population, low serum Se levels were positively associated with the prevalence of diabetes. Until findings from prospective studies and randomized controlled trials are available, Se intake, including Se supplementation, should be recommended for primary or secondary diabetes prevention in populations with inadequate selenium status.     

FGFR1 amplification is associated with poor prognosis and smoking in non-small-cell lung cancer

FGFR1 amplification has been identified recently as an important therapeutic target in non-small-cell lung cancer (NSCLC), particularly squamous cell carcinoma (SqCC). However, data from previous studies on the clinical implications of FGFR amplification in NSCLC are inconsistent. We evaluated FGFR1 gene copy number (GCN) in 369 cases of surgically resected NSCLC using five previously reported criteria and investigated associations between clinicopathologic parameters and FGFR1 amplification. FGFR1 amplification was found in 32/369 (8.7 %) of NSCLC and was more frequent in SqCC (18.0 % in SqCC, 3.0 % in adenocarcinoma; p?p?FGFR1 amplification was significantly associated with shorter overall survival (OS, 58.6 vs 80.0 months; p?=?0.033) and shorter disease-free survival (DFS, 58.5 vs 80.0 months; p?=?0.042) in patients with SqCC, but this was not statistically significant on multivariate analysis (OS: hazard ratio [HR]?=?1.79, 95 % confidence interval [CI]?=?0.83–3.87, p?=?0.139; DFS: HR?=?1.73, 95 % CI?=?0.93–3.21, p?=?0.081). The correlation between FGFR1 amplification and protein expression was poor (rho?=?0.08; p?=?0.123). These results suggest that FGFR1 amplification is associated with smoking history and squamous cell carcinoma histology and might indicate poor prognosis.     

In breast cancer patients sentinel lymph node metastasis characteristics predict further axillary involvement

The aim of the study was to correlate various primary tumor characteristics with lymph node status, to examine sentinel lymph node (SLN) metastasis size and non-SLN axillary involvement, to look for a cut-off size/number value possibly predicting additional axillary involvement with more accuracy and to examine the relationship of SLN metastasis size to overall survival. Of 301 patients who underwent SLN biopsy, 75 had positive SLNs. The size of the metastases was measured. For different size categories, association with the prevalence of non-SLN metastases was assessed. Associations between metastasis size and tumor characteristics and overall survival (OS) were studied. The prevalence of axillary lymph node (ALN) involvement was not significantly different between cases with micrometastasis or macrometastasis in SLNs (p?=?0.124). However, for metastases larger than 6, 7, and 8 mm, the prevalence of ALN involvement was significantly higher (p?=?0.046, 0.022, and 0.025). OS was significantly lower in SLN-positive than in SLN-negative cases (p?=?0.0375). Primary tumor size larger than 20 mm was associated with a significantly higher incidence of SLN metastasis (p?<?0.001), and primary tumor size over 26 mm was associated with additional positive non-SLN (p?<?0.001). Higher mitotic index (≥7) in primary tumors was significantly (p?<?0.001) associated with ALN involvement in SLN-positive cases, whereas higher Ki67 labeling index was not significantly correlated with SLN or ALN involvement. Lymphovascular invasion (LVI) in primary tumors was significantly correlated with SLN positivity (p?<?0.001) but not with further ALN involvement or OS. Tumor size and LVI are predictive for SLN metastasis. Mitotic index, primary tumor size, and larger volume SLN involvement are determinants of further ALN involvement. SLN metastasis size over 6 mm is a strong predictor of further axillary involvement. OS is shorter in the presence of positive SLN.     

Clinical Utility of KAP-1 Expression in Thyroid Lesions

Although there are evidences of the involvement of KAP-1 in other tumors, data on differentiated thyroid carcinomas (DTC) are still lacking. We aimed to evaluate KAP-1 clinical utility in the diagnosis and prognosis of DTC. We used both visual immunohistochemistry and a semiquantitative analysis to evaluate KAP-1 expression in 230 thyroid carcinomas and 131 noncancerous thyroid nodules. There were 43 follicular carcinomas (FC) and 187 papillary thyroid carcinomas (PTC), including 130 classic (CPTC), 4 tall cells (TCPTC), and 53 follicular variants (FVPTC). Patients were followed up for 53.8?±?41 months. They were classified as free-of-disease (142 cases) or poor outcome (25 cases—10 deaths), according to their serum Tg levels and image evidences. KAP-1 was identified in 78 % PTC, 75 % TCPTC, 74 % FC, 72 % FVPTC, 55 % FA, 44 % hyperplasia, and 11 % normal thyroid tissues. A ROC analysis identified malignant nodules with 69 % sensitivity and 75 % specificity, using a cutoff of 73.19. In addition to distinguishing benign from malignant thyroid tissues (p?<?0.0001), KAP-1 expression differentiated CPTC from nodular hyperplasia (p?<?0.0001), CPTC from FA (p?=?0.0028), FVPTC from hyperplasia (p?=?0.0039), and FC from hyperplasia (p?=?0.0025). Furthermore, KAP-1 was more expressed in larger tumors (>4 cm; p?=?0.0038) and in individuals who presented recurrences/metastases (p?=?0.0130). We suggest that KAP-1 may help diagnose thyroid nodules, characterize follicular-patterned thyroid lesions, and identify individuals with poor prognosis.     

Human herpes virus co-infection is associated with mortality in HIV-negative patients with Pneumocystis jirovecii pneumonia

The purpose of this investigation was to characterize the management and prognosis of severe Pneumocystis jirovecii pneumonia (PJP) in human immunodeficiency virus (HIV)-negative patients. An observational cohort study of HIV-negative adults with PJP documented by bronchoalveolar lavage (BAL) through Gomori–Grocott staining or immunofluorescence, admitted to one intensive care unit (ICU) for acute respiratory failure, was undertaken. From 1990 to 2010, 70 patients (24 females, 46 males) were included, with a mean age of 58.6?±?18.3 years. The mean Simplified Acute Physiology Score (SAPS)-II was 36.9?±?20.4. Underlying conditions included hematologic malignancies (n?=?21), vasculitis (n?=?13), and solid tumors (n?=?13). Most patients were receiving systemic corticosteroids (n?=?63) and cytotoxic drugs (n?=?51). Not a single patient received trimethoprim–sulfamethoxazole as PJP prophylaxis. Endotracheal intubation (ETI) was required in 42 patients (60.0 %), including 38 with acute respiratory distress syndrome (ARDS). In-ICU mortality was 52.9 % overall, reaching 80.9 % and 86.8 %, respectively, for patients who required ETI and for patients with ARDS. In the univariate analysis, in-ICU mortality was associated with SAPS-II (p?=?0.0131), ARDS (p?<?0.0001), shock (p?<?0.0001), and herpes simplex virus (HSV) or cytomegalovirus (CMV) on BAL (p?=?0.0031). In the multivariate analysis, only ARDS was associated with in-ICU mortality (odds ratio [OR] 23.4 [4.5–121.9], p?<?0.0001). PJP in non-HIV patients remains a serious disease with high in-hospital mortality. Pulmonary co-infection with HSV or CMV may contribute to fatal outcome.     

Association of E-selectin Gene Polymorphism (S128R) with Ischemic Stroke and Stroke Subtypes

E-selectin is an important inflammatory cytokine involved in the pathogenesis of various diseases such as atherosclerosis and stroke. We investigated the association of E-selectin gene polymorphism (S128R) with ischemic stroke and its subtypes. We studied 610 patients with ischemic stroke and 610 age- and sex-matched healthy controls. The ischemic stroke was classified according to Trial of Org10172 in Acute Stroke Treatment (TOAST). E-selectin gene polymorphism (S128R) was determined by polymerase chain reaction–restriction fragment length polymorphism technique. We found statistically significant difference in the genotypic distribution between patients and controls (for AC vs. AA, χ ²?=?49.5; p?<?0.001, odds ratio?=?5.47(95 % CI, 3.25–9.21). A significant difference was observed in the frequency of C and A alleles in patients and controls (for C vs. A, χ ²?=?47.4; p?<?0.001, odds ratio?=?5.13 (95 % CI, 3.06–8.57). Multiple logistic regression analysis revealed that the most predictive risk factor for stroke was AC genotype (adjusted odds ratio?=?1.450 (95 % CI, 1.23–2.75) and p?=?0.001), hypertension, smoking, and diabetes (p?=?0.001 in each case). We also found a significant association of AC genotype with intracranial large artery atherosclerosis (p?<?0.01, odds ratio?=?9.37, (95 % CI, 5.31–16.5) and small artery occlusion (p?<?0.0001, odds ratio?=?9.81 (95 % CI, 4.94–19.4). Our results indicate that the individuals bearing AC genotype of E-selectin gene polymorphism (S128R) are more prone to stroke than AA genotype.     

Cancer stem cell characteristics, ALDH1 expression in the invasive front of nasopharyngeal carcinoma

The invasive tumor front underlies the biological aggressiveness and epithelial–mesenchymal transition (EMT) in various human malignances. However, the molecular and biological characteristics of invasive tumor front in NPC have rarely been described. Additionally, the features of cancer stem cells (CSCs) in the invasive front of tumors and its correlation with EMT also remain elusive. Our study was to investigate the expression of CSCs marker aldehyde dehydrogenase 1 (ALDH1) in the invasive front of nasopharyngeal carcinoma (NPC) and its clinical significance. Immunohistochemistry was mainly used to detect ALDH1 expression in the invasive front of NPC. The relationship between ALDH1 expression and EMT-associated markers was also examined. ALDH1 expression in the invasive front correlated strongly with lymphatic invasion (p?<?0.001), T classification (p?=?0.001), M classification (p?<?0.001), clinical stage (p?<?0.001), and local recurrence (p?=?0.008). ALDH1 overexpression in the invasive front contributed to worse survival of NPC, particularly in patients with early stage (T1-T2 or N0-N1) (p?<?0.001 and p?=?0.002, respectively), though it was not an independent prognostic factor (p?=?0.196). Furthermore, in the invasive front of NPC, ALDH1 expression correlated significantly with EMT-related biomarkers E-cadherin (p?=?0.026), Vimentin (p?<?0.001), Periostin (p?<?0.001), and Snail (p?<?0.001), but not with β-catenin (p?=?0.143). Our findings demonstrate first that ALDH1 expression in the invasive front links closely with EMT characteristics and tumor aggressiveness, which might provide a useful prognostic marker for NPC patients.     

Association of Toll-Like Receptor 4 Polymorphisms with Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is characterized by a chronic low-grade inflammatory state. Toll-like receptor 4 (TLR4) is a critical mediator of innate immunity. Polymorphisms in TLR4 gene have been shown to be associated with impaired inflammatory response. Here, we investigated the association of TLR4 polymorphisms with T2DM. Four TLR4 polymorphisms (+986A/G, +1196C/T, +3725G/C, and +11367G/C) were genotyped in a total number of 822 T2DM patients and 835 healthy controls. Results showed that the +986A/G and +1196C/T polymorphisms did not exist in the Han Chinese population. The prevalence of TLR4 +3725GC and CC genotypes were significantly decreased in T2DM cases than in controls (odds ratio (OR)?=?0.62, 95 % confidence interval (CI)?=?0.50–0.78, p?=?3.48?×?10^?5, and OR?=?0.36, 95 % CI?=?0.22–0.59, p?=?1.55?×?10^?5, respectively). Also, the frequency of TLR4 +3725C allele was significantly lower in T2DM patients (p?=?2.46?×?10^?9). When analyzing the TLR4 +11367G/C polymorphism, the +11367CC genotype revealed lower numbers in patients compared to healthy controls (OR?=?0.46, 95 % CI?=?0.27–0.78, p?=?0.0032). Analysis of the clinical features on the control subjects demonstrated no correlations between these TLR4 polymorphisms and sex, age, body mass index, etc. (p?>?0.05). In conclusion, these data indicate that TLR4 +3725G/C and +11367G/C polymorphisms may be novel protective factors against T2DM in the Chinese population.     

Peri-Infarct Zone Characterized by Cardiac Magnetic Resonance Imaging is Directly Associated with the Inflammatory Activity During Acute Phase Myocardial Infarction

Enhanced systemic inflammatory activity (SIA) during myocardial infarction (MI) and the extent of the peri-infarct zone characterized by cardiac magnetic resonance imaging (CMRi) are both associated with increased risk of life-threatening arrhythmias and sudden cardiac death. The present study investigated the existence of association between these two phenomena in 98 patients (55?±?10 years) with ST segment elevation MI. Plasma levels of C-reactive protein (CRP), interleukin-2 (IL-2), and tumor necrosis factor (TNF) were measured on admission (D1) and on the fifth day post-MI (D5). CMRi was performed 2 weeks after MI to quantify peri-infarct zone (PIZ). Between D1 and D5, the increase in CRP (6.0 vs. 5.6 times; p?=?0.02), IL-2 (3.6 vs. 3.4 times; p?=?0.04) and tumor necrosis factor type α (TNF-α; 4.6 vs. 3.9 times; p?=?0.001) were higher in patients with PIZ above the median than in the counterparts. PIZ was correlated with CRP-D5 (r?=?0.69), delta-CRP (r?=?0.7), IL-2-D5 (r?=?0.5), delta-IL-2 (r?=?0.6), TNF-α (r?=?0.5), delta-TNF-α (r?=?0.4; p?=?0.0001). Enhanced activation of SIA during the acute phase of MI is directly related with generation of PIZ.     

Expression of podocalyxin-like protein is an independent prognostic biomarker in resected esophageal and gastric adenocarcinoma

Background

Podocalyxin-like protein (PODXL) is a cell surface transmembrane glycoprotein, the expression of which has been associated with poor prognosis in a range of malignancies. The aim of this study was to investigate the impact of PODXL expression on survival in esophageal and gastric adenocarcinoma.

Methods

The study cohort consists of a consecutive series of 174 patients with esophageal (including the gastroesophageal junction) or gastric adenocarcinoma, surgically treated between 2006 and 2010 and not subjected to neoadjuvant treatment. Immunohistochemical expression of PODXL was assessed in tissue microarrays with cores from primary tumors, lymph node metastases, intestinal metaplasia and adjacent normal epithelium. Survival analyses were performed on patients with no distant metastases and no macroscopic residual tumor.

Results

In the majority of cases, expression of PODXL was significantly higher in cancer cells compared to normal epithelial cells and was significantly associated with lymph node metastases and high grade tumors. In esophageal adenocarcinoma, Kaplan-Meier analyses revealed that patients with PODXL negative tumors had a superior time to recurrence (TTR) and overall survival (OS) compared to patients with PODXL positive tumors. In gastric adenocarcinoma, patients with PODXL negative tumors had a superior TTR and a trend towards an improved OS. In esophageal and gastric adenocarcinoma combined, the prognostic significance of PODXL expression on TTR was confirmed in unadjusted Cox regression analysis (HR?=?5.36, 95 % CI 1.68-17.06, p?=?0.005) and remained significant in the adjusted model (HR?=?3.39, 95 % CI 1.01-11.35, p?=?0.048). Moreover, the impact of PODXL expression on OS was also confirmed in unadjusted analysis (HR?=?2.52, 95 % CI 1.31-4.85, p?=?0.006) and remained significant in the adjusted model (HR?=?2.03, 95 % CI 1.04-3.98, p?=?0.039).

Conclusions

In esophageal and gastric adenocarcinoma, PODXL expression is an independent prognostic biomarker for reduced time to recurrence and poor overall survival. This is the first report on the prognostic role of PODXL in esophageal adenocarcinoma and validates recent findings in gastric cancer.