Altered Localization of p120 Catenin in the Cytoplasm Rather than the Membrane Correlates with Poor Prognosis in Esophageal Squamous Cell Carcinoma

Background

P120 catenin (p120ctn), a regulator of cell adhesion, has previously been found in many malignancies, and suggested a role in invasion, metastasis and survival. The aim of this study was to investigate correlations between altered localization of p120ctn and clinical-pathological characteristics in esophageal squamous cell carcinoma (ESCC).

Methods

Immunohistochemical staining for p120^ctn was performed on tissue samples from 118 patients with ESCC. The expression of p120^ctn was scored for intensity and cellular localization by Image-pro Plus 6.0. Correlations between immunohistochemical staining of p120^ctn and pathological characteristics and clinical prognosis were determined using SPSS 18.0 software.

Results

Membrane expression of p120^ctn in ESCCs was lower than that in adjacentnormal esophageal epithelial tissues (P = 0.041), while overall cellular expression of p120^ctn was not different between the two tissue types (P = 0.787). Furthermore, neither overall cellular expression nor localized membrane expression was associated with histological and clinical variables. The high ratio of membrane expression to overall cellular expression (M/C) of p120^ctn was inversely associated with lymph node invasion (P = 0.001), tumor differentiation (P = 0.012) and advanced tumor stage (P = 0.005); however, it was poorly associated with T stage (P = 0.274). The high M/C ratio of p120^ctn was inversely correlated with poor survival; the 5-year OS (overall survival) and the 5-year DFS (disease free survival) for the high M/C ratio group were significantly higher than those of the low M/C ratio group (41.0% vs. 6.7%, P = 0.000; 44.1% vs. 24.9%, P = 0.007). Both the M/C ratio of p120^ctn and N status were independent variables for the prediction of overall survival (P = 0.007 and P = 0.027). The M/C of p120^ctn predicted a 0.49-fold risk of ESCC death (p = 0.007, 95% CI 0.29–0.83).

Conclusions

The reduced M/C ratio of p120^ctn acted as an independent prognostic factor for ESCC patient survival and for the migration and invasive behavior of the disease.     

Postoperative Capecitabine with Concurrent Intensity-Modulated Radiotherapy or Three-Dimensional Conformal Radiotherapy for Patients with Stage II and III Rectal Cancer

Background

The aim of this study was to evaluate the survival outcomes and toxicity of postoperative chemoradiotherapy with capecitabine and concurrent intensity-modulated radiotherapy (IMRT) or three-dimensional conformal radiotherapy (3D-CRT) in patients with stage II and III rectal cancer.

Patients

We recruited 184 patients with pathologically proven, stage II or III rectal cancer. Following total mesorectal excision (TME), the patients were treated with capecitabine and concurrent IMRT/3D-CRT. The treatment regimen consisted of two cycles of oral capecitabine (1600 mg/m²/day), administered twice daily from day 1–14 of radiotherapy, followed by a 7-day rest. The median pelvic dose was 50 Gy in 25 fractions. Oxaliplatin-based adjuvant chemotherapy was administered after the chemoradiotherapy.

Results

The 5-year overall survival, disease-free survival and locoregional control (LRC) rates were 85.1%, 80% and 95.4%, respectively. Grade 3 and 4 toxicities were observed in 28.3% of patients during treatment. Grade 3 or 4 late toxicity, including neurotoxicity or gastrointestinal toxicity, was only observed in nine patients (4.9%).

Conclusions

This study demonstrated that capecitabine chemotherapy with concurrent IMRT/3D-CRT following TME is safe, is well tolerated and achieves superior LRC and favorable survival rates, with acceptable toxicity.     

Robotic versus Open Radical Cystectomy: An Updated Systematic Review and Meta-Analysis

Objective

To critically review the currently available evidence of studies comparing robot-assisted radical cystectomy (RARC) with open radical cystectomy (ORC).

Methods

A comprehensive review of the literature from Pubmed, Web of Science and Scopus was performed in April 2014. All relevant studies comparing RARC with ORC were included for further screening. A pooled meta-analysis of all comparative studies was performed and publication bias was assessed by a funnel plot.

Results

Nineteen studies were included for the analysis, including a total of 1779 patients (787 patients in the RARC group and 992 patients in the ORC group). Although RARC was associated with longer operative time (p <0.0001), patients in this group might benefit from significantly lower overall perioperative complication rates within 30 days and 90 days (p = 0.005 and 0.0002, respectively), more lymph node yields (p = 0.009), less estimated blood loss (p <0.00001), lower need for perioperative and intraoperative transfusions (p <0.0001 and <0.0001, respectively), and shorter postoperative length of stay (p = 0.0002). There was no difference between two groups regarding positive surgical margin rates (p = 0.19).

Conclusions

RARC appears to be an efficient alternative to ORC with advantages of less perioperative complications, more lymph node yields, less estimated blood loss, lower need for transfusions, and shorter postoperative length of stay. Further studies should be performed to compare the long-term oncologic outcomes between RARC and ORC.     

Biogeographic Ancestry Is Associated with Higher Total Body Adiposity among African-American Females: The Boston Area Community Health Survey

Objectives

The prevalence of obesity is disproportionately higher among African-Americans and Hispanics as compared to whites. We investigated the role of biogeographic ancestry (BGA) on adiposity and changes in adiposity in the Boston Area Community Health Survey.

Methods

We evaluated associations between BGA, assessed via Ancestry Informative Markers, and adiposity (body mass index (BMI), percent body fat (PBF), and waist-to-hip ratio (WHR)) and changes in adiposity over 7 years for BMI and WHR and 2.5 years for PBF, per 10% greater proportion of BGA using multivariable linear regression. We also examined effect-modification by demographic and socio-behavioral variables.

Results

We observed positive associations between West-African ancestry and cross-sectional BMI (percent difference=0.62%; 95% CI: 0.04%, 1.20%), and PBF (β=0.35; 95% CI: 0.11, 0.58). We also observed significant effect-modification of the association between West-African ancestry and BMI by gender (p-interaction: <0.002) with a substantially greater association in women. We observed no main associations between Native-American ancestry and adiposity but observed significant effect-modification of the association with BMI by diet (p-interaction: <0.003) with inverse associations among participants with higher Healthy Eating Scores. No associations were observed between BGA and changes in adiposity over time.

Conclusion

Findings support that West-African ancestry may contribute to high prevalence of total body adiposity among African-Americans, particularly African-American women.     

Neuropsychological Investigation in Chinese Patients with Progressive Muscular Atrophy

Background

Progressive muscular atrophy (PMA) is a rare type of degenerative motor neuron disease (MND) of which the onset happens in adult period. Despite its well-defined clinical characteristics, its neuropsychological profile has remained poorly understood, considering the consensus of cognitive and behavioral impairment reached in amyotrophic lateral sclerosis (ALS).

Methods

We conducted a cross-sectional evaluation of Chinese PMA patients with a series of comprehensive batteries emphasizing the executive and attention function, and covering other domains of memory, language, visuospatial function, calculation and behavior as well. Their performances were compared with those of age- and education-matched ALS and healthy controls (HC).

Results

21 patients newly diagnosed with PMA were consecutively enrolled into our ALS and other MND registry platform, accounting for 14.7% of all the incident MND cases registered during the same period. 20 patients who completed the neuropsychological batteries were included into analysis. Compared with HC, PMA performed significantly worse in maintenance function of attention, while they exhibited quantitative similarity to ALS in all behavioral inventories and neuropsychological tests except the time for Stroop interference effect.

Conclusion

PMA could display mild cognitive dysfunction in the same frontal-mediated territory of ALS but in a lesser degree, whereas they did not differ from ALS behaviorally.     

A Locked Nucleic Acid (LNA)-Based Real-Time PCR Assay for the Rapid Detection of Multiple Bacterial Antibiotic Resistance Genes Directly from Positive Blood Culture

Bacterial strains resistant to various antibiotic drugs are frequently encountered in clinical infections, and the rapid identification of drug-resistant strains is highly essential for clinical treatment. We developed a locked nucleic acid (LNA)-based quantitative real-time PCR (LNA-qPCR) method for the rapid detection of 13 antibiotic resistance genes and successfully used it to distinguish drug-resistant bacterial strains from positive blood culture samples. A sequence-specific primer-probe set was designed, and the specificity of the assays was assessed using 27 ATCC bacterial strains and 77 negative blood culture samples. No cross-reaction was identified among bacterial strains and in negative samples, indicating 100% specificity. The sensitivity of the assays was determined by spiking each bacterial strain into negative blood samples, and the detection limit was 1–10 colony forming units (CFU) per reaction. The LNA-qPCR assays were first applied to 72 clinical bacterial isolates for the identification of known drug resistance genes, and the results were verified by the direct sequencing of PCR products. Finally, the LNA-qPCR assays were used for the detection in 47 positive blood culture samples, 19 of which (40.4%) were positive for antibiotic resistance genes, showing 91.5% consistency with phenotypic susceptibility results. In conclusion, LNA-qPCR is a reliable method for the rapid detection of bacterial antibiotic resistance genes and can be used as a supplement to phenotypic susceptibility testing for the early detection of antimicrobial resistance to allow the selection of appropriate antimicrobial treatment and to prevent the spread of resistant isolates.     

Apoptotic Cell Death Induced by Resveratrol Is Partially Mediated by the Autophagy Pathway in Human Ovarian Cancer Cells

Resveratrol (trans-3,4,5’ –trihydroxystilbene) is an active compound in food, such as red grapes, peanuts, and berries. Resveratrol exhibits an anticancer effect on various human cancer cells. However, the mechanism of resveratrol-induced anti-cancer effect at the molecular level remains to be elucidated. In this study, the mechanism underlying the anti-cancer effect of resveratrol in human ovarian cancer cells (OVCAR-3 and Caov-3) was investigated using various molecular biology techniques, such as flow cytometry, western blotting, and RNA interference, with a major focus on the potential role of autophagy in resveratrol-induced apoptotic cell death. We demonstrated that resveratrol induced reactive oxygen species (ROS) generation, which triggers autophagy and subsequent apoptotic cell death. Resveratrol induced ATG5 expression and promoted LC3 cleavage. The apoptotic cell death induced by resveratrol was attenuated by both pharmacological and genetic inhibition of autophagy. The autophagy inhibitor chloroquine, which functions at the late stage of autophagy, significantly reduced resveratrol-induced cell death and caspase 3 activity in human ovarian cancer cells. We also demonstrated that targeting ATG5 by siRNA also suppressed resveratrol-induced apoptotic cell death. Thus, we concluded that a common pathway between autophagy and apoptosis exists in resveratrol-induced cell death in OVCAR-3 human ovarian cancer cells.     

A phylo-functional core of gut microbiota in healthy young Chinese cohorts across lifestyles,geography and ethnicities

Structural profiling of healthy human gut microbiota across heterogeneous populations is necessary for benchmarking and characterizing the potential ecosystem services provided by particular gut symbionts for maintaining the health of their hosts. Here we performed a large structural survey of fecal microbiota in 314 healthy young adults, covering 20 rural and urban cohorts from 7 ethnic groups living in 9 provinces throughout China. Canonical analysis of unweighted UniFrac principal coordinates clustered the subjects mainly by their ethnicities/geography and less so by lifestyles. Nine predominant genera, all of which are known to contain short-chain fatty acid producers, co-occurred in all individuals and collectively represented nearly half of the total sequences. Interestingly, species-level compositional profiles within these nine genera still discriminated the subjects according to their ethnicities/geography and lifestyles. Therefore, a phylogenetically diverse core of gut microbiota at the genus level may be commonly shared by distinctive healthy populations as functionally indispensable ecosystem service providers for the hosts.