Limiting pool and actin architecture controls myosin cluster sizes in adherent cells.

The actomyosin cytoskeleton generates mechanical forces that power important cellular processes, such as cell migration, cell division, and mechanosensing. Actomyosin self-assembles into contractile networks and bundles that underlie force generation and transmission in cells. A central step is the assembly of the myosin II filament from myosin monomers, regulation of which has been extensively studied. However, myosin filaments are almost always found as clusters within the cell cortex. While recent studies characterized cluster nucleation dynamics at the cell periphery, how myosin clusters grow on stress fibers remains poorly characterized. Here, we utilize a U2OS osteosarcoma cell line with endogenously tagged myosin II to measure the myosin cluster size distribution in the lamella of adherent cells. We find that myosin clusters can grow with Rho-kinase (ROCK) activity alone in the absence of myosin motor activity. Time-lapse imaging reveals that myosin clusters grow via increased myosin association to existing clusters, which is potentiated by ROCK-dependent myosin filament assembly. Enabling myosin motor activity allows further myosin cluster growth through myosin association that is dependent on F-actin architecture. Using a toy model, we show that myosin self-affinity is sufficient to recapitulate the experimentally observed myosin cluster size distribution, and that myosin cluster sizes are determined by the pool of myosin available for cluster growth. Together, our findings provide new insights into the regulation of myosin cluster sizes within the lamellar actomyosin cytoskeleton.

Decreased expression of BRCA1-associated protein 1 predicts unfavorable survival in gastric adenocarcinoma.

BRCA1-associated protein 1 (BAP1) has been reported as a novel tumor suppressor, while in gastric adenocarcinoma, the function of this protein was still await to be uncovered. Based on a large group of patients with gastric adenocarcinoma, our study aimed to have a further understanding about the correlation of BAP1 expression and patients' clinical outcomes. We performed quantitative PCR and Western blot to examine BAP1 expression in 38 cases of gastric adenocarcinoma samples and adjacent non-cancerous tissues. Immunochemistry was used to evaluate BAP1 expression in a large cohort of 474 paraffin-embedded specimens. The clinical and prognostic significance of BAP1 expression was statistically analyzed. Postoperative survival between groups was using Kaplan-Meier analysis. BAP1 was overexpressed in paracancerous normal mucosa compared with gastric cancer. Decreased BAP1 expression was associated with higher histologic grade (P = 0.044), tumor infiltration (P < 0.001), metastasis status (P = 0.023), and TNM stage (P < 0.001). Patients with low expression of BAP1 had shorter overall survival compared with those with high expression (P < 0.001). Patients' survival in stage N0 could be stratified by the expression of BAP1. Multivariate analysis showed that in gastric adenocarcinoma, BAP1 expressing level was an independent prognostic factor (RR = 0.575, P < 0.001). Decreased expression of BAP1 suggests pessimistic prognosis for gastric adenocarcinoma patients. Further studies are warranted.

Effect of Mechanical Damage in Green-Making Process on Aroma of Rougui Tea.

Rougui Tea (RGT) is a typical Wuyi Rock Tea (WRT) that is favored by consumers for its rich taste and varied aroma. The aroma of RGT is greatly affected by the process of green-making, but its mechanism is not clear. Therefore, in this study, fresh leaves of RGT in spring were picked, and green-making (including shaking and spreading) and spreading (unshaken) were, respectively, applied after sun withering. Then, they were analyzed by GC-TOF-MS, which showed that the abundance of volatile compounds with flowery and fruity aromas, such as nerolidol, jasmine lactone, jasmone, indole, hexyl hexanoate, (E)-3-hexenyl butyrate and 1-hexyl acetate, in green-making leaves, was significantly higher than that in spreading leaves. Transcriptomic and proteomic studies showed that long-term mechanical injury and dehydration could activate the upregulated expression of genes related to the formation pathways of the aroma, but the regulation of protein expression was not completely consistent. Mechanical injury in the process of green-making was more conducive to the positive regulation of the allene oxide synthase (AOS) branch of the α-linolenic acid metabolism pathway, followed by the mevalonate (MVA) pathway of terpenoid backbone biosynthesis, thus promoting the synthesis of jasmonic acid derivatives and sesquiterpene products. Protein interaction analysis revealed that the key proteins of the synthesis pathway of jasmonic acid derivatives were acyl-CoA oxidase (ACX), enoyl-CoA hydratase (MFP2), OPC-8:0 CoA ligase 1 (OPCL1) and so on. This study provides a theoretical basis for the further explanation of the formation mechanism of the aroma substances in WRT during the manufacturing process.

Local monomer levels and established filaments potentiate non-muscle myosin 2 assembly.

The ability to dynamically assemble contractile networks is required throughout cell physiology, yet direct biophysical mechanisms regulating non-muscle myosin 2 filament assembly in living cells are lacking. Here, we use a suite of dynamic, quantitative imaging approaches to identify deterministic factors that drive myosin filament appearance and amplification. We find that actin dynamics regulate myosin assembly, but that the static actin architecture plays a less clear role. Instead, remodeling of actin networks modulates the local myosin monomer levels and facilitates assembly through myosin:myosin-driven interactions. Using optogenetically controlled myosin, we demonstrate that locally concentrating myosin is sufficient to both form filaments and jump-start filament amplification and partitioning. By counting myosin monomers within filaments, we demonstrate a myosin-facilitated assembly process that establishes filament stacks prior to partitioning into clusters that feed higher-order networks. Together, these findings establish the biophysical mechanisms regulating the assembly of non-muscle contractile structures that are ubiquitous throughout cell biology.

Duck compound probiotics fermented diet alters the growth performance by shaping the gut morphology, microbiota and metabolism.

Dietary absorption and digestion are influenced by the microbiota, morphology, and digestive enzymes of intestines, and fermentation is a popular and effective technique to enhance animal rearing growth performance. This study aims to explore the pivotal role of Muscovy duck probiotics fermented feedstuff (FF) in altering the growth performance by reshaping gut morphology, microorganisms and metabolism. The findings showed that FF considerably raised the levels of fatty acids (FA) and small peptides (7-19AA) in the diet. Further feeding trial data reveals that FF greatly increased the Muscovy duck average daily gain (ADG) but had no effect on their daily feed intake (DFI), and the FCR significantly dropped (P < 0.05). Additionally, it was evident that FF improved the integrity of the intestinal mucosa in Muscovy duck by increasing villus height, villus height-to-crypt depth ratio, and lowering crypt depth. Then, in comparison to the control group (NC), there was a significant increase in the gene expression of the mucosal tight junction proteins Occludin, Claudin-1, and Zo-1 in the intestine of Muscovy duck. Additionally, there was higher expression of the mucosal transport channels SGLT-1, PepT1, AQP2, AQP3, and AQP10 in the similarly colon site, jejunum, and duodenum. Furthermore, in AB-PAS/PAS-stained duodenum, jejunum, ileum, and similarly colon site, FF markedly increased relative mucus output and goblet cells while decreasing epithelial cell apoptosis. Following 16S sequencing data indicated that the intestinal microbiota was altered and the diversity and richness of gut microbes was greatly enhanced by FF. Particularly, the boost of core probiotics, such as Rothia of duodenum, Limosilactobacillus and Lentilactobacillus of jejunum, Lactococcus and Rothia of ileum, Ligilactobacillus and Entocuccus of similarly colon site, Gallibacterium of caecum. And reduced potentially pathogenic bacteria (Campylobacter, Prevotellaceae, Clostridia-vadinBB60, and Oscillospira). Nontargeted metabolomics assay for intestinal content confirmed an increased organic acids (oxidanesulfonic acid, cholic acid, gallic acid, coumaric acid, pipecollc acid, 13s-hydroxyoctadecadienoic acid) and glycosides metabolites (5-hydroxydantrolene, 3-hydroxyguanfacine glucuronide, acetylleucine, astragalin, xanthosine, taxiphylin, sinapine, denudatine, penylalanyl-tyrosine and phenylalanyl-valine). These findings demonstrated that FF, a viable option to improve Muscovy duck growth performance through reconstructed intestinal morphology, microorganisms, and metabolism, subsequently promoted the gut health and increased diet digestion and absorption. The study that is being presented offers scientific proof that FF might be a useful strategy for improving Muscovy duck growth performance.

Limiting Pool and Actin Architecture Controls Myosin Cluster Sizes in Adherent Cells.

The actomyosin cytoskeleton generates mechanical forces that power important cellular processes, such as cell migration, cell division, and mechanosensing. Actomyosin self-assembles into contractile networks and bundles that underlie force generation and transmission in cells. A central step is the assembly of the myosin II filament from myosin monomers, regulation of which has been extensively studied. However, myosin filaments are almost always found as clusters within the cell cortex. While recent studies characterized cluster nucleation dynamics at the cell periphery, how myosin clusters grow on stress fibers remains poorly characterized. Here, we utilize a U2OS osteosarcoma cell line with endogenously tagged myosin II to measure the myosin cluster size distribution in the lamella of adherent cells. We find that myosin clusters can grow with Rho-kinase (ROCK) activity alone in the absence of myosin motor activity. Time-lapse imaging reveals that myosin clusters grow via increased myosin association to existing clusters, which is potentiated by ROCK-dependent myosin filament assembly. Enabling myosin motor activity allows further myosin cluster growth through myosin association that is dependent on F-actin architecture. Using a toy model, we show that myosin self-affinity is sufficient to recapitulate the experimentally observed myosin cluster size distribution, and that myosin cluster sizes are determined by the pool of myosin available for cluster growth. Together, our findings provide new insights into the regulation of myosin cluster sizes within the lamellar actomyosin cytoskeleton.

Metabolic improvements of novel microbial fermentation on black tea by Eurotium cristatum.

Due to its traditional fermentation, there are obvious limits on the quality improvements in black tea. However, microbial fermentation can provide an abundance of metabolites and improve the flavor of tea. The "golden flower" fungi are widely used in the microbial fermentation of tea and has unique uses in healthcare. To further explore the improvements in black tea quality achieved via microbial fermentation, we used widely targeted metabolomics and metagenomics analyses to investigate the changes in and effects of metabolites and other microorganisms during the interaction between the "golden flower" fungi and black tea. Five key flavor metabolites were detected, the levels of catechin, epigallocatechin gallate, (-)-epicatechin gallate were decreased by different degrees after the inoculation of the "golden flower" fungus, whereas the levels of caffeine and (+)-gallocatechin increased. Botryosphaeriaceae, Botryosphaeriales, Dothideomycetes, Aspergillaceae, Trichocomaceae, and Lecanoromycetes play a positive role in the black tea fermentation process after inoculation with the "golden flower" fungi. D-Ribose can prevent hypoxia-induced apoptosis in cardiac cells, and it shows a strong correlation with Botryosphaeriaceae and Botryosphaeriales. The interaction between microorganisms and metabolites is manifested in tryptophan metabolism, starch and sucrose metabolism, and amino sugar and nucleotide sugar metabolism. In conclusion, the changes in metabolites observed during the fermentation of black tea by "golden flower" fungi are beneficial to human health. This conclusion extends the knowledge of the interaction between the "golden flower" fungi and black tea, and it provides important information for improving the quality of black tea.

Local Monomer Levels and Established Filaments Potentiate Non-Muscle Myosin 2 Assembly.

The ability to dynamically assemble contractile networks is required throughout cell physiology, yet the biophysical mechanisms regulating non-muscle myosin 2 filament assembly in living cells are lacking. Here we use a suite of dynamic, quantitative imaging approaches to identify deterministic factors that drive myosin filament appearance and amplification. We find that actin dynamics regulate myosin assembly, but that the actin architecture plays a minimal direct role. Instead, remodeling of actin networks modulates the local myosin monomer levels and facilitates assembly through myosin:myosin driven interactions. Using optogenetically controlled myosin, we demonstrate that locally concentrating myosin is sufficient to both form filaments and jump-start filament amplification and partitioning. By counting myosin monomers within filaments, we demonstrate a myosin-facilitated assembly process that establishes sub-resolution filament stacks prior to partitioning into clusters that feed higher-order networks. Together these findings establish the biophysical mechanisms regulating the assembly of non-muscle contractile structures that are ubiquitous throughout cell biology.

Species boundaries in the messy middle-A genome-scale validation of species delimitation in a recently diverged lineage of coastal fog desert lichen fungi.

Species delimitation among closely related species is challenging because traditional phenotype-based approaches, for example, using morphology, ecological, or chemical characteristics, may not coincide with natural groupings. With the advent of high-throughput sequencing, it has become increasingly cost-effective to acquire genome-scale data which can resolve previously ambiguous species boundaries. As the availability of genome-scale data has increased, numerous species delimitation analyses, such as BPP and SNAPP+Bayes factor delimitation (BFD*), have been developed to delimit species boundaries. However, even empirical molecular species delimitation approaches can be biased by confounding evolutionary factors, for example, hybridization/introgression and incomplete lineage sorting, and computational limitations. Here, we investigate species boundaries and the potential for micro-endemism in a lineage of lichen-forming fungi, Niebla Rundel & Bowler, in the family Ramalinaceae by analyzing single-locus and genome-scale data consisting of (a) single-locus species delimitation analysis using ASAP, (b) maximum likelihood-based phylogenetic tree inference, (c) genome-scale species delimitation models, e.g., BPP and SNAPP+BFD, and (d) species validation using the genealogical divergence index (gdi). We specifically use these methods to cross-validate results between genome-scale and single-locus datasets, differently sampled subsets of genomic data and to control for population-level genetic divergence. Our species delimitation models tend to support more speciose groupings that were inconsistent with traditional taxonomy, supporting a hypothesis of micro-endemism, which may include morphologically cryptic species. However, the models did not converge on robust, consistent species delimitations. While the results of our analysis are somewhat ambiguous in terms of species boundaries, they provide a valuable perspective on how to use these empirical species delimitation methods in a nonmodel system. This study thus highlights the challenges inherent in delimiting species, particularly in groups such as Niebla, with complex, relatively recent phylogeographic histories.

Prognostic value of non-invasive serum Cytokeratin 18 detection in gastrointestinal cancer: a meta-analysis.

Background: Gastrointestinal cancer is one of the most common neoplasms. Cytokeratin 18(CK18) is widely expressed in many different organs and cancers. Emerging data suggested conflicting results about the role of CK18 during carcinogenesis. The aim of this study is to systematically review the prognostic value of circulating CK18 (M65) and caspase-Cleaved CK18 (M30) in digestive cancers. Materials and Methods: We searched major database for manuscripts reporting the effect of pretreatment CK18 on survival of digestive cancer patients. Revman5.3 and R were the software used for analysis. Pooled multivariable-adjusted hazard ratios (HR) for overall survival (OS) were calculated in all patients and many different subgroup analyses by stratifying on tumor type, metastasis stage, and ethnicity. Results: 11 original studies were included for analysis. A low level of M30 and M65 were shown to be a protective factor for all cancer patients (HR 0.49, 95%CI 0.33-0.73, P=0.0003; HR 0.48, 95% CI 0.32-0.70, P =0.0001, respectively). The low M30 remained to be a protective factor for metastasized cancer patients while M65 had no statistically significant correlation with prognosis. Conclusions: Non-invasive total and cleaved CK18 level detection by ELISA could be potentially a useful predictor of prognosis of digestive cancer patients. Further studies are warranted to investigate the molecular mechanisms of CK18.

Population genomic analyses of RAD sequences resolves the phylogenetic relationship of the lichen-forming fungal species Usneaantarctica and Usneaaurantiacoatra.

Neuropogonoid species in the lichen-forming fungal genus Usnea exhibit great morphological variation that can be misleading for delimitation of species. We specifically focused on the species delimitation of two closely-related, predominantly Antarctic species differing in the reproductive mode and representing a so-called species pair: the asexual U.antarctica and the sexual U.aurantiacoatra. Previous studies have revealed contradicting results. While multi-locus studies based on DNA sequence data provided evidence that these two taxa might be conspecific, microsatellite data suggested they represent distinct lineages. By using RADseq, we generated thousands of homologous markers to build a robust phylogeny of the two species. Furthermore, we successfully implemented these data in fine-scale population genomic analyses such as DAPC and fineRADstructure. Both Usnea species are readily delimited in phylogenetic inferences and, therefore, the hypothesis that both species are conspecific was rejected. Population genomic analyses also strongly confirmed separated genomes and, additionally, showed different levels of co-ancestry and substructure within each species. Lower co-ancestry in the asexual U.antarctica than in the sexual U.aurantiacoatra may be derived from a wider distributional range of the former species. Our results demonstrate the utility of this RADseq method in tracing population dynamics of lichens in future analyses.

Clinical significance of plasma D-dimer and fibrinogen in digestive cancer: A systematic review and meta-analysis.

BACKGROUND: Abnormalities of coagulation and fibrinolysis are frequently observed in cancer patients. Emerging data suggested that plasma D-dimer and fibrinogen levels correlated with tumor stage and prognosis in several cancer types. The aim of this study is to systematically review the prognostic value of plasma D-dimer and fibrinogen in digestive cancers. MATERIALS AND METHODS: We searched major database for manuscripts reporting the effect of pretreatment plasma d-dimer or fibrinogen on survival of digestive cancer patients. Revman5.3 and R were the software used for analysis. Pooled multivariable-adjusted hazard ratios (HR) for overall survival (OS) were calculated in all patients and many different subgroup analyses by stratifying on metastasis stage, tumor type, ethnicity, cutoff points and average age. RESULTS: 37 original studies were included for analysis. Increased levels of plasma D-dimer showed stronger association with worse OS than fibrinogen in digestive cancer (HR = 2.06, 95% CI 1.79-2.38; HR = 1.60, 95% CI 1.44-1.79). The highest adverse impacts of elevated plasma D-dimer and fibrinogen on OS were revealed in colorectal cancer (HR = 2.32, 95% CI 1.89-2.85; HR = 2.20, 95% CI 1.24-3.90). The negative prognostic effects of high plasma D-dimer enhanced in metastatic patients when compared with non-metastatic digestive cancer patients, while high plasma D-dimer was more predictive non-metastatic patients. CONCLUSIONS: Both of pretreatment plasma D-dimer and fibrinogen were robust predictors of poor survival in digestive cancer patients with different traits. Further studies are warranted to verify their roles on cancer prognosis.

GP73 level determines chemotherapeutic resistance in human hepatocellular carcinoma cells.

Objective GP73 is a new hepatocellular carcinoma (HCC) marker, which is highly expressed in hepatocellular carcinoma and closely relates to prognosis. This study was to investigate the effects of GP73 on cellular proliferation, apoptosis, oxaliplatin (OXA) resistance and secretory clusterin (sCLU) of HCC cells. Materials and Methods Western blot and immunofluorescence was used to detect the expression of GP73 in 8 types of commonly used HCC cell lines. Drug resistance was induced by increasing concentration gradient method. The drug-resistant human HCC cell lines underwent GP73 overexpression or inhibition. Flow cytometry were used to detect the proliferation and apoptosis of HCC cell lines. The changes of sCLU were detected by enzyme-linked immunosorbent assay (ELISA). Results The expression of GP73 in MHC-97H cells was the highest and in Hep3B cells the lowest. The expression of GP73 was found further elevated in OXA-resistant MHC-97H cells. After the knockdown of GP73 in OXA-resistant 97H cells, the IC50 of OXA decreased and the ability of cell proliferation decreased significantly. After over-expression of GP73 in OXA-resistant Hep3B cells, the IC50 of OXA increased and the cell proliferation ability increased, showing that GP73 is critical for OXA resistant in HCC cell lines; No significant change of sCLU level in GP73 overexpressed Hep3B and GP73 blocked MHCC-97H were identified. Conclusion The expression level of GP73 is critical for the resistance of OXA in HCC cell lines.

A high plasma D-dimer level predicts poor prognosis in gynecological tumors in East Asia area: a systematic review and meta-analysis.

High pre-treatment plasma D-dimer levels have been reported as a factor associated with a poor prognosis in different types of malignancies, including pancreatic, gastric, colorectal, lung, and nasopharyngeal carcinoma. Here, we performed a meta-analysis to determine the association of plasma D-dimer levels and long term survival in gynecological cancers, including ovarian, cervical and endometrial carcinoma. We searched all eligible publications in PubMed and Web of Science Databases up to August 2016. Primary outcomes, including overall survival (OS), disease-free survival and hazard ratios (HR) of were extracted and analyzed. Heterogeneity and publication bias were also assessed. A total of 7 eligible studies with 1112 cases were included in this study and all included studies are conducted in East Asia area. We found that gynecological cancer patients with high D-dimer demonstrates a much lower 5-year survival rate than those with low D-dimer levels (OR 4.12, 95% CI 3.04-5.58, P<0.00001). No significant heterogeneity is found (I2 = 10 %; P = 0.35). Importantly, pooled analysis showed that high plasma D-dimer levels are predictive of a shorter OS in gynecological cancers (HR 2.09, 95% CI 1.59-2.74). No heterogeneity is observed (I2=5%, P=0.39). Additionally, a subgroup analysis of ovarian cancer is conducted. In conclusion, this meta-analysis showed that a high plasma D-dimer level predicts poor prognosis in gynecological tumors.

The Role of GOLPH3L in the Prognosis and NACT response in Cervical Cancer.

Background: We previously reported GOLPH3L is a novel oncogene associated with ovarian cancer. The role of GOLPH3L in cervical cancer and its cellular functions has not been determined. This study investigated clinical significance of GOLPH3L and potential proteins and pathways associated with GOLPH3L in cervical squamous cell carcinoma. Methods: Immunohistochemistry and western blot were used to examine the expression of GOLPH3L in cervical squamous cell carcinoma tissue specimens and adjacent non-cancerous tissues. The clinical and prognostic significance of GOLPH3L expression was statistically analyzed. Cell proliferation rate, cell cycle progression, apoptosis and cisplatin response in GOLPH3L silenced SiHa and HeLa cells were also examined. Phospho-antibody array was used to identify changes in protein phosphorylation and the corresponding signaling pathways associated with these changes. Results: GOLPH3L overexpressed in cervical cancer tissue specimens compared with normal adjacent non-cancerous tissues. Increased GOLPH3L expression was associated with FIGO staging (P=0.033), cervical stromal invasion (P=0.037), cervical canal stromal invasion (P=0.027), lymph node metastasis (P=0.016) and positive surgical margins (P=0.015). Patients with lower expression of GOLPH3L demonstrated longer progression-free survival and overall survival compared with those with higher expression. The tissue samples from patients who poorly responded to neoadjuvant chemotherapy (NACT) exhibited increased GOLPH3L expression levels compared with tissue samples from patients who achieved a pathologic complete response (pCR). Patients with lower GOLPH3L expression level, poorer tumor differentiation, shorter NACT treatment intervals and smaller tumor sizes were more likely to achieve a pCR after NACT. Knockdown GOLPH3L in cells was associated with an induction of cell cycle arrest, increased apoptosis and cisplatin sensitivity, and a reduction in cellular viability. Phospho-antibody array suggested GOLPH3L plays a role in mediating cell cycle arrest. Conclusions: This study provides a potential biomarker for predicting prognosis and NACT response in patients with cervical squamous cell carcinoma. The functional role of GOLPH3L in cervical cancer merits further investigation.

APE1 overexpression is associated with poor survival in patients with solid tumors: a meta-analysis.

APE1 is known as a key mediator of DNA damage repair pathways, and its clinical significance in different types of cancer is well studied. Herein, we performed a meta-analysis to determine the association of APE1 expression and survival in different types of solid cancer. We searched all eligible publications in PubMed, Web of Science and Embase platforms from inception to January 2017 and found 15 relevant manuscripts. Overall survival (OS), 12- and 36-month survival rates, and hazard ratios (HRs) were extracted and analyzed. Heterogeneity and publication bias were also assessed. A subgroup analysis of the different subcellular locations of APE1 was also conducted. Patients with higher APE1 levels demonstrated lower 12- and 36-month survival rates than those with low APE1 levels (HR 2.00, 95% CI 1.33-3.00, P = 0.0009; HR 1.84, 95% CI 1.19-2.84, P = 0.006). Importantly, the pooled analysis showed that high levels of APE1 predict shorter OS (HR 1.44, 95% CI 1.13-1.83, P = 0.003). Subgroup analysis revealed that both nuclear and cytoplasmic expression levels of APE1 are important indicators of poor prognosis in solid tumors.

Dacomitinib, a new pan-EGFR inhibitor, is effective in killing ovarian cancer cells.

OBJECTIVE: Aberrant epidermal growth factor receptor (EGFR) is involved in a variety of cancers and its inhibitors have been studied for over a decade. We aim to investigate the effects of dacomitinib, a second generation pan-EGFR inhibitor, on ovarian cancer cells. METHODS: By immunohistochemistry, we studied the clinical significance of EGFR expression in epithelial ovarian cancer (EOC). The correlations between EGFR expression and the clinicopathological variables of patients with EOC were assessed using Pearson's X2 test. Kaplan-Meier analysis was used to compare the postoperative survival between groups of patients with EOC with varying levels of EGFR expression. MTT, caspase assay, cell apoptosis analysis, autophagy analysis, cell cycle analysis, and western blotting were used to investigate various effects of dacomitinib in cell proliferation, apoptosis, and associated molecular pathways. RESULTS: High expression of EGFR was found to be associated with poor prognosis of patients with EOC. EGFR, P-AKT, and P-ERK were inhibited after treatment of dacomitinib in both SKOV3 and OV4 cells. Activations of caspase activities, apoptosis, and autophagy were also observed and confirmed by western blot: caspase 9, LC3, and Bax levels were elevated, while Bcl-2 and Bcl-xl were down-regulated. The percentage of cancer cells in the S and G2 phases of the cell cycle significantly decreased after treatment. Cdk1 and Cdk2 protein levels declined after dacomitinib treatment; epithelial-mesenchymal transition (EMT) was inhibited, which was confirmed by observing E-cadherin, N-cadherin, and slug inhibition. Additionally, dacomitinib significantly increased chemotherapy sensitivity in chemotherapeutic resistant ovarian cell lines, C13 and 2780CP. CONCLUSION: Our data showed that increased expression of EGFR is associated with poor prognosis of patients with EOC and dacomitinib may act as a novel, useful chemotherapy drug. Further studies are warranted.

Reduced Expression of FADS1 Predicts Worse Prognosis in Non-Small-Cell Lung Cancer.

OBJECTIVE: Fatty acid desaturase 1 is a member of the fatty acid desaturase, which is related to a number of diseases. However, its role in cancers remains unclear. This study was to explore the clinical importance of FADS1 expression in non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Immunochemistry was used to evaluate FADS1 expressions in 216 paraffin-embedded specimens. The expression of FADS1 was divided into high and low groups. The clinical and prognostic significance of FADS1 expression was analyzed statistically by Kaplan-Meier estimate and Cox regression model. RESULTS: FADS1 overexpressed in normal bronchial mucosa compared with non-small-cell lung cancer. Reduced FADS1 expression was associated with tumor size (P=0.023) and histological grade (P<0.0001). Patients with lower expression of FADS1 had shorter overall survival and disease free survival (P=0.001 and P=0.002). Multivariate analysis showed FADS1 expression was an independent prognostic factor in NSCLC (P=0.011). CONCLUSION: Reduced expression of FADS1 suggests pessimistic prognosis for NSCLC patients. Further studies are warranted.

Increased APOBEC3B Predicts Worse Outcomes in Lung Cancer: A Comprehensive Retrospective Study.

Lung cancer ranks as the most common and lethal malignancy in America and worldwide. APOBEC3B is a newly identified DNA cytosine deaminase, which is supposed to function as a major source of DNA mutation in many different tumors. In this study, we combine the data of online databases and two hundred and twenty-one primary non-small-cell lung carcinoma (NSCLC) specimens from Sun Yat-sen University Cancer Center to investigate, for the first time, the clinical role of APOBEC3B in lung cancer. We found that the APOBEC3 expression was commonly elevated in NSCLC tissues and overexpression of APOBEC3B was correlated with unfavorable prognosis of the patients with NSCLC. Furthermore, APOBEC3B expression was associated with nodal status, TNM staging and adjuvant chemotherapy of the patients with NSCLC. Further research is warranted.

GOLPH3L is a Novel Prognostic Biomarker for Epithelial Ovarian Cancer.

OBJECTIVE: Golgi phosphoprotein 3 (GOLPH3) is a highly conserved membrane protein that is involved in a variety of cancers such as colorectal cancer, gastric cancer, ovarian cancer, and breast cancer. GOLPH3L is a paralog of GOLPH3. Although these proteins share a similar amino acid sequence, much less is known regarding the subcellular functions or effects of GOLPH3L on cancer compared with GOLPH3. The role of GOLPH3L in epithelial ovarian cancer (EOC) has not yet been investigated. METHODS: Using western blot, PCR and immunohistochemical analyses, we studied the clinical significance of GOLPH3L expression in EOC. The correlations between GOLPH3L expression and the clinicopathological variables of patients with EOC were assessed using Pearson's χ2 test. Kaplan-Meier analysis was used to compare the postoperative survival between groups of patients with EOC with varying levels of GOLPH3L expression. RESULTS: High expression of GOLPH3L was more frequently observed in EOC tissues than in corresponding adjacent non-tumor tissues. The expression of GOLPH3L correlated closely with pre-operative CA125 level (P=0.031). Univariate analysis showed that age, FIGO stage, pre-operative cancer antigen (CA) 125, pre-operative albumin concentration (AC), optimal cytoreductive surgery (CRS) and GOLPH3L expression correlate significantly with overall survival (OS). Multivariate analysis revealed that GOLPH3L expression was an independent prognostic factor for OS of patients with EOC (102 months versus 72 months; P=0.013). What's more, knocked down of GOLPH3L with small interfering RNA (siRNA) technology of OVCAR3 and SKOV3 cell lines reduced cell viability obviously, compared to the negative control and blank control groups. CONCLUSIONS: Our data show that increased expression of GOLPH3L is associated with poor prognosis of patients with EOC and may act as a novel, useful and independent prognostic indicator. Therefore, further studies are warranted.