Positivity bias in judging ingroup members' emotional expressions.

PubMed

Lazerus, Talya; Ingbretsen, Zachary A; Stolier, Ryan M; Freeman, Jonathan B; Cikara, Mina

2016-12-01

We investigated how group membership impacts valence judgments of ingroup and outgroup members' emotional expressions. In Experiment 1, participants, randomized into 2 novel, competitive groups, rated the valence of in- and outgroup members' facial expressions (e.g., fearful, happy, neutral) using a circumplex affect grid. Across all emotions, participants judged ingroup members' expressions as more positive than outgroup members' expressions. In Experiment 2, participants categorized fearful and happy expressions as being either positive or negative using a mouse-tracking paradigm. Participants exhibited the most direct trajectories toward the "positive" label for ingroup happy expressions and an initial attraction toward positive for ingroup expressions of fear, with outgroup emotion trajectories falling in between. Experiment 3 replicated Experiment 2 and demonstrated that the effect could not be accounted for by targets' gaze direction. Overall, people judged ingroup faces as more positive, regardless of emotion, both in deliberate and implicit judgments. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Expression and copy number gains of the RET gene in 631 early and mid stage non‐small cell lung cancer cases

PubMed Central

Tan, Ling; Hu, Yerong; Tao, Yongguang; Wang, Bin; Xiao, Jun; Tang, Zhenjie; Lu, Ting

2018-01-01

Background To identify whether RET is a potential target for NSCLC treatment, we examined the status of the RET gene in 631 early and mid stage NSCLC cases from south central China. Methods RET expression was identified by Western blot. RET‐positive expression samples were verified by immunohistochemistry. RET gene mutation, copy number variation, and rearrangement were analyzed by DNA Sanger sequencing, TaqMan copy number assays, and reverse transcription‐PCR. ALK and ROS1 expression levels were tested by Western blot and EGFR mutation using Sanger sequencing. Results The RET‐positive rate was 2.5% (16/631). RET‐positive expression was related to poorer tumor differentiation (P < 0.05). In the 16 RET‐positive samples, only two samples of moderately and poorly differentiated lung adenocarcinomas displayed RET rearrangement, both in RET‐KIF5B fusion partners. Neither ALK nor ROS1 translocation was found. The EGFR mutation rate in RET‐positive samples was significantly lower than in RET‐negative samples (P < 0.05). Conclusion RET‐positive expression in early and mid stage NSCLC cases from south central China is relatively low and is related to poorer tumor differentiation. RET gene alterations (copy number gain and rearrangement) exist in all RET‐positive samples. RET‐positive expression is a relatively independent factor in NSCLC patients, which indicates that the RET gene may be a novel target site for personalized treatment of NSCLC. PMID:29473341

[Expression of hnRNPK in gastric carcinoma and its relationship with Helicobacter pylori L-form infection].

PubMed

Zhao, Yan; Jin, Xin; Tian, Tian; Yu, Dong-hong

2011-10-01

To investigate the expression feature of heterogeneous nuclear ribonucleoprotein K in gastric carcinoma and its clinical significance, and to explore the relationship between hnRNPK expression and Helicobacter pylori L-form infection. The expression of hnRNPK protein was examined in 100 cases of gastric carcinoma, 50 paracancerous gastric tissues and 30 matched normal gastric mucosa by Elivision immunohistochemistry and hnRNPK-mRNA by in situ hybridization. Hp-L was detected with Gram staining and immunohistochemical staining. The positive rates of hnRNPK protein and mRNA in gastric carcinoma were 82.0% and 86.0%, respectively, significantly higher than those in the paracancerous gastric tissues and normal controls (P < 0.05). The expression of hnRNPK protein was significantly correlated with histological differentiation, TNM stage and lymph node metastasis (P < 0.05). The positive rates of Hp-L in the three groups were 67.0%, 58.0% and 23.3%, respectively. The positive rate of Hp-L in gastric carcinoma had no significant correlation with it in the paracancerous gastric tissues, but was significantly higher than it in the normal controls (P < 0.05). In gastric carcinoma, the expression of hnRNPK protein was higher in cases of Hp-L positive patients than those of Hp-L negative cases (P < 0.05). Positive correlation existed between the expression of hnRNPK protein and Hp-L infection (r = 0.391, P < 0.01). There is a higher expression of hnRNPK in gastric carcinoma. Hp-L infection may be associated with the up-regulated hnRNPK expression. The two factors may play a synergetic role in gastric carcinogenesis.

Instructor Reputation: An Expectancy Relationship Involving Student Ratings and Achievement.

ERIC Educational Resources Information Center

Perry, Raymond P.

1979-01-01

Instructor expressiveness and lecture content were combined with instructor reputation in a 2 X 2 X 2 factorial design to assess interaction effects. Results indicated that reputation interacted with expressiveness but not content, in which students rated positive, high-expressive instructors more favorably than negative, high-expressive…

MMP-7 expression may influence the rate of distant recurrences and disease-specific survival in HPV-positive oropharyngeal squamous cell carcinoma.

PubMed

Vento, Seija I; Jouhi, Lauri; Mohamed, Hesham; Haglund, Caj; Mäkitie, Antti A; Atula, Timo; Hagström, Jaana; Mäkinen, Laura K

2018-05-02

The objective of this study was to determine if matrix metalloproteinase-7 (MMP-7) expression is related to human papilloma virus (HPV) status, clinical parameters, and outcome in oropharyngeal squamous cell carcinoma (OPSCC). Tumor tissue specimens from 201 OPSCC patients treated with curative intent were available for immunohistochemistry, and the samples were stained with monoclonal MMP-7 antibody. All the patients were followed up at least 3 years or until death. MMP-7 expression did not differ between HPV-positive and HPV-negative patients. MMP-7 was not prognostic among patients with HPV-negative OPSCC. In the HPV-positive subgroup, patients with moderate, high, or very high MMP-7 expression had significantly worse 5-year disease-specific survival (DSS) (56.6%) than patients with absent, or low MMP-7 expression (77.2%), and MMP-7 expression appeared as a prognostic factor in the multivariate analysis. In addition, among HPV-positive OPSCC with moderate, high, or very high MMP-7 expression, the 5-year distant recurrence-free survival was significantly lower (69.6%) than in those who had low or absent MMP-7 expression (97.5%). Our results suggest that among HPV-positive OPSCC patients, high MMP-7 expression is related to worse 5-year DSS and increased rate of distant recurrences.

Diminished facial emotion expression and associated clinical characteristics in Anorexia Nervosa.

PubMed

Lang, Katie; Larsson, Emma E C; Mavromara, Liza; Simic, Mima; Treasure, Janet; Tchanturia, Kate

2016-02-28

This study aimed to investigate emotion expression in a large group of children, adolescents and adults with Anorexia Nervosa (AN), and investigate the associated clinical correlates. One hundred and forty-one participants (AN=66, HC= 75) were recruited and positive and negative film clips were used to elicit emotion expressions. The Facial Activation Coding system (FACES) was used to code emotion expression. Subjective ratings of emotion were collected. Individuals with AN displayed less positive emotions during the positive film clip compared to healthy controls (HC). There was no significant difference between the groups on the Positive and Negative Affect Scale (PANAS). The AN group displayed emotional incongruence (reporting a different emotion to what would be expected given the stimuli, with limited facial affect to signal the emotion experienced), whereby they reported feeling significantly higher rates of negative emotion during the positive clip. There were no differences in emotion expression between the groups during the negative film clip. Despite this individuals with AN reported feeling significantly higher levels of negative emotions during the negative clip. Diminished positive emotion expression was associated with more severe clinical symptoms, which could suggest that these individuals represent a group with serious social difficulties, which may require specific attention in treatment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Heparanase mRNA expression and point mutation in hepatocellular carcinoma

PubMed Central

Chen, Xiao-Peng; Liu, Yin-Bib; Rui, Jing; Peng, Shu-You; Peng, Cheng-Hong; Zhou, Zi-Yan; Shi, Liang-Hui; Shen, Hong-Wei; Xu, Bin

2004-01-01

AIM: To explore the expression of heparanase mRNA and point mutation in hepatocellular carcinoma (HCC). METHODS: Reverse transcription polymerase chain reaction was used to measure the expression of heparanase mRNA in the primary tumor tissues and surrounding liver tissues of 33 HCC patients. T-A cloning and sequencing were used to detect whether there was any mutation in the amplified PCR products. RESULTS: The expression of heparanase mRNA was positive in 16 primary tumor tissues of HCC, and the positive rate was 48.5%, which was significantly higher than that in the surrounding liver parenchyma (P < 0.01). The positive rate for heparanase gene in high-tendency to metastatic recurrence group (71.4%, 10/14) was obviously higher than that in low-tendency to metastatic recurrence group (31.6%, 6/19) (P = 0.023). The positive rate for heparanase gene in patients with metastatic recurrence during postoperative follow-up (78.6%, 11/14) was also significantly higher than that in those without metastatic recurrence (21.4%, 3/14) (P = 0.003). Sequence analysis of the HPA PCR products was made in 7 patients, and 2-point mutations were found in 4 patients, one of which was sense mutation, neither base insertion nor deletion was detected. The mutation rate was 57.1% (4/7). CONCLUSION: The expression rate of heparanase mRNA increases in HCC, and HPA mRNA may be one of the reliable markers for the metastatic activity gained by the liver tumor cells and could be used clinically in predicting metastatic recurrence of HCC. Point mutation may be one of the causes for enhanced heparanase mRNA expression. PMID:15334672

[Dectection of G3BP and CD44v6 in the tissues of laryngeal squamous cell carcinoma and their clinical significance].

PubMed

Luo, Dahu; Lou, Weihua

2017-07-01

Objective To study the expressions of RNA-binding Ras-GAP SH3 binding protein (G3BP) and tumor stem cell marker CD44v6 in laryngeal squamous cell carcinoma and their correlations with angiogenesis. Methods We collected the cancer tissues and corresponding paracancerous tissues from 56 patients with laryngeal squamous cell carcinoma. The expressions of G3BP and CD44v6 proteins were detected by Western blotting in cancer tissues and corresponding paracancerous tissues; the expressions of G3BP, CD44v6 and vascular endothelial growth factor A (VEGF-A) were tested by immunohistochemistry. Thereafter, we compared the positive expression rates of G3BP and CD44v6 between in cancer tissues and in normal tissues, analyzed the correlations between the expressions of G3BP, CD44v6 and the laryngeal squamous cell carcinoma features as well as their correlations with microvessel density (MVD) that was determined by FVIIIAg immunohistochemistry. Results Western blotting showed that the expressions of G3BP and CD44v6 proteins in the laryngeal squamous cell carcinoma were higher than those in the paracancerous tissues. Immunohistochemistry showed that compared with the paracancerous tissues, G3BP, CD44v6 and VEGF-A expressions (the positive rates are 58.9%, 53.6%, 46.4%, respectively) were higher in cancer tissues. The positive rates of G3BP and CD44v6 in cancer tissues were related with the clinical stage, recurrence or metastasis, and lymph node metastasis of laryngeal squamous cell carcinoma, but had nothing to do with patients' age and tumor size. Pearson correlation analysis showed the expressions of both G3BP and CD44v6 were positively correlated with VEGF-A (r=0.741, r=0.756). MVD values were significantly higher in the G3BP and CD44v6 positive cases than in paracancerous tissues, but there was no difference in MVD between those without G3BP and CD44v6 positive expressions and the paracancerous tissues. Conclusion The positive expression rates of G3BP and CD44v6 in laryngeal squamous cell carcinoma tissues are very high, and they have a close relationship with the clinical prognosis. They may raise the VEGF-A expression so as to promote angiogenesis, and then accelerate the development of the laryngeal squamous cell carcinoma.

Context shapes social judgments of positive emotion suppression and expression.

PubMed

Kalokerinos, Elise K; Greenaway, Katharine H; Casey, James P

2017-02-01

It is generally considered socially undesirable to suppress the expression of positive emotion. However, previous research has not considered the role that social context plays in governing appropriate emotion regulation. We investigated a context in which it may be more appropriate to suppress than express positive emotion, hypothesizing that positive emotion expressions would be considered inappropriate when the valence of the expressed emotion (i.e., positive) did not match the valence of the context (i.e., negative). Six experiments (N = 1,621) supported this hypothesis: when there was a positive emotion-context mismatch, participants rated targets who suppressed positive emotion as more appropriate, and evaluated them more positively than targets who expressed positive emotion. This effect occurred even when participants were explicitly made aware that suppressing targets were experiencing mismatched emotion for the context (e.g., feeling positive in a negative context), suggesting that appropriate emotional expression is key to these effects. These studies are among the first to provide empirical evidence that social costs to suppression are not inevitable, but instead are dependent on context. Expressive suppression can be a socially useful emotion regulation strategy in situations that call for it. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

[Evaluation of mimetic expression of schizophrenic and depressed patients by the psychiatrist].

PubMed

Schneider, F; Mattes, R; Adam, B; Heimann, H

1992-01-01

Facial videos of schizophrenic and depressive patients and of healthy controls when watching both funny and horror films and during emotionally positive or negative interviews were rated by psychiatrists (experts) and students (novices). The observers' task was to rate joy, fear, sadness, and expressivity on a 7-point unipolar intensity scale. The soundless facial videos were presented to each observer for exactly 2.5 min. The observer groups did not differ significantly in their ratings except for sadness. Psychiatrists consistently rated expressed sadness as less intense than students. Facial expressivity and joy were rated as less intense in both patient groups in comparison with healthy controls. Depressives expressed significantly more sadness.

Event-related brain responses to emotional words, pictures, and faces – a cross-domain comparison

PubMed Central

Bayer, Mareike; Schacht, Annekathrin

2014-01-01

Emotion effects in event-related brain potentials (ERPs) have previously been reported for a range of visual stimuli, including emotional words, pictures, and facial expressions. Still, little is known about the actual comparability of emotion effects across these stimulus classes. The present study aimed to fill this gap by investigating emotion effects in response to words, pictures, and facial expressions using a blocked within-subject design. Furthermore, ratings of stimulus arousal and valence were collected from an independent sample of participants. Modulations of early posterior negativity (EPN) and late positive complex (LPC) were visible for all stimulus domains, but showed clear differences, particularly in valence processing. While emotion effects were limited to positive stimuli for words, they were predominant for negative stimuli in pictures and facial expressions. These findings corroborate the notion of a positivity offset for words and a negativity bias for pictures and facial expressions, which was assumed to be caused by generally lower arousal levels of written language. Interestingly, however, these assumed differences were not confirmed by arousal ratings. Instead, words were rated as overall more positive than pictures and facial expressions. Taken together, the present results point toward systematic differences in the processing of written words and pictorial stimuli of emotional content, not only in terms of a valence bias evident in ERPs, but also concerning their emotional evaluation captured by ratings of stimulus valence and arousal. PMID:25339927

Relation between premorbid personality and patterns of emotion expression in mid- to late-stage dementia.

PubMed

Magai, C; Cohen, C I; Culver, C; Gomberg, D; Malatesta, C

1997-11-01

Twenty-seven nursing home patients with mid- to late-stage dementia participated in a study of the relation between preillness personality, as indexed by attachment and emotion regulation style, and current emotional behavior. Preillness measures were completed by family members and current assessments of emotion were supplied by nursing home aides and family members; in addition, emotion was coded during a family visit using an objective coding system for facial emotion expressions. Attachment style was found to be related to the expression of positive affect, with securely attached individuals displaying more positive affect than avoidantly attached individuals. In addition, high ratings on premorbid hostility were associated with higher rates of negative affect and lower rates of positive affect. These findings indicate that premorbid aspects of personality show continuity over time, even in mid- to late-stage dementia.

A gene expression signature of Retinoblastoma loss-of-function predicts resistance to neoadjuvant chemotherapy in ER-positive/HER2-positive breast cancer patients.

PubMed

Risi, Emanuela; Grilli, Andrea; Migliaccio, Ilenia; Biagioni, Chiara; McCartney, Amelia; Guarducci, Cristina; Bonechi, Martina; Benelli, Matteo; Vitale, Stefania; Biganzoli, Laura; Bicciato, Silvio; Di Leo, Angelo; Malorni, Luca

2018-07-01

HER2-positive (HER2+) breast cancers show heterogeneous response to chemotherapy, with the ER-positive (ER+) subgroup deriving less benefit. Loss of retinoblastoma tumor suppressor gene (RB1) function has been suggested as a cardinal feature of breast cancers that are more sensitive to chemotherapy and conversely resistant to CDK4/6 inhibitors. We performed a retrospective analysis exploring RBsig, a gene signature of RB loss, as a potential predictive marker of response to neoadjuvant chemotherapy in ER+/HER2+ breast cancer patients. We selected clinical trials of neoadjuvant chemotherapy ± anti-HER2 therapy in HER2+ breast cancer patients with available information on gene expression data, hormone receptor status, and pathological complete response (pCR) rates. RBsig expression was computed in silico and correlated with pCR. Ten studies fulfilled the inclusion criteria and were included in the analysis (514 patients). Overall, of 211 ER+/HER2+ breast cancer patients, 49 achieved pCR (23%). The pCR rate following chemotherapy ± anti-HER2 drugs in patients with RBsig low expression was significantly lower compared to patients with RBsig high expression (16% vs. 30%, respectively; Fisher's exact test p = 0.015). The area under the ROC curve (AUC) was 0.62 (p = 0.005). In the 303 ER-negative (ER-)/HER2+ patients treated with chemotherapy ± anti-HER2 drugs, the pCR rate was 43%. No correlation was found between RBsig expression and pCR rate in this group. Low expression of RBsig identifies a subset of ER+/HER2+ patients with low pCR rates following neoadjuvant chemotherapy ± anti-HER2 therapy. These patients may potentially be spared chemotherapy in favor of anti-HER2, endocrine therapy, and CDK 4/6 inhibitor combinations.

Positive Selection Underlies Faster-Z Evolution of Gene Expression in Birds

PubMed Central

Dean, Rebecca; Harrison, Peter W.; Wright, Alison E.; Zimmer, Fabian; Mank, Judith E.

2015-01-01

The elevated rate of evolution for genes on sex chromosomes compared with autosomes (Fast-X or Fast-Z evolution) can result either from positive selection in the heterogametic sex or from nonadaptive consequences of reduced relative effective population size. Recent work in birds suggests that Fast-Z of coding sequence is primarily due to relaxed purifying selection resulting from reduced relative effective population size. However, gene sequence and gene expression are often subject to distinct evolutionary pressures; therefore, we tested for Fast-Z in gene expression using next-generation RNA-sequencing data from multiple avian species. Similar to studies of Fast-Z in coding sequence, we recover clear signatures of Fast-Z in gene expression; however, in contrast to coding sequence, our data indicate that Fast-Z in expression is due to positive selection acting primarily in females. In the soma, where gene expression is highly correlated between the sexes, we detected Fast-Z in both sexes, although at a higher rate in females, suggesting that many positively selected expression changes in females are also expressed in males. In the gonad, where intersexual correlations in expression are much lower, we detected Fast-Z for female gene expression, but crucially, not males. This suggests that a large amount of expression variation is sex-specific in its effects within the gonad. Taken together, our results indicate that Fast-Z evolution of gene expression is the product of positive selection acting on recessive beneficial alleles in the heterogametic sex. More broadly, our analysis suggests that the adaptive potential of Z chromosome gene expression may be much greater than that of gene sequence, results which have important implications for the role of sex chromosomes in speciation and sexual selection. PMID:26067773

Helping Yourself by Offering Help: Mediators of Expressive Helping in Survivors of Hematopoietic Stem Cell Transplant.

PubMed

Williamson, Timothy J; Stanton, Annette L; Austin, Jane E; Valdimarsdottir, Heiddis B; Wu, Lisa M; Krull, Jennifer L; Rini, Christine M

2017-10-01

A randomized experiment by Rini et al. (Health Psychol. 33(12):1541-1551, 2014) demonstrated that expressive helping, which involves three expressive writing sessions regarding hematopoietic stem cell transplant, followed by one writing session directed toward helping other stem cell transplant recipients, reduced psychological distress and bothersome physical symptoms among stem cell transplant recipients with elevated survivorship problems, relative to a neutral writing control condition. The current study evaluated whether word use reflective of emotional expression, cognitive processing, and change in perspective mediates the effects of expressive helping. The essays of 67 stem cell transplant recipients with high survivorship problems were analyzed with Linguistic Inquiry and Word Count. Multiple mediation modeling was used to test the hypothesized mechanisms of expressive helping on distress and bothersome physical symptoms. Relative to the control condition, expressive helping produced significant reductions in psychological distress and marginal reductions in physical symptom bother in the analyzed subset of participants from the parent study. Results indicated that positive emotion word use significantly mediated effects of expressive helping on reduced distress, but only for participants who used average (compared to above or below average) rates of negative emotion words. Cognitive processing and change in perspective did not significantly mediate benefits of expressive helping. Expressive helping carried its positive effects on distress through participants' higher expression of positive emotions when coupled with moderate rates of negative emotions. Findings highlight the benefit of expressing both positive and negative emotions in stressful situations.

High-risk and low-risk human papilloma virus in association to spontaneous preterm labor: a case-control study in a tertiary center, Egypt.

PubMed

Mosbah, Alaa; Barakat, Rafik; Nabiel, Yasmin; Barakat, Ghada

2018-03-01

This study aimed to detect the correlation between human papillomavirus (HPV) and spontaneous preterm labor in Egyptian women and its association to the human papilloma viral load and MPP2 gene expression. We performed an observational comparative case-control study in Department of Obstetric and Gynecology, Mansoura University Hospitals over women presented with spontaneous preterm labor, besides females admitted for giving birth at full term to detect conserved sequence in HPV-L1 gene (GP5/GP6) followed by genotype detection of high- and low-risk HPVs with quantification of the viral load and the MMP2 gene expression using real-time polymerase chain reaction (PCR). The prevalence of HPV was 18.1% in preterm females, but only 4% in full-term women (p value = 0.019*). Twenty percent were PCR positive for HPV 16 and 40% for HPV 18 whereas none of the control was positive for any of the studied high-risk genotypes. Thirty percent were PCR positive for HPV 6 and 10% were positive for HPV 11. MMP2 gene expression was significantly higher in preterm than full term. Human papilloma viral load was found to be positively correlated to the rate of MMP2 expression and the gestational age was significantly related to the viral load and the rate of expression of MMP2 gene. Human pabilloma virus especially high-risk genotypes was correlated to spontaneous preterm labor in Egyptian females through increasing early expression of MMP2 gene. The time of occurrence of preterm labor was affected by the viral load and so the rate of expression of MMP2 gene.

Facial expression system on video using widrow hoff

NASA Astrophysics Data System (ADS)

Jannah, M.; Zarlis, M.; Mawengkang, H.

2018-03-01

Facial expressions recognition is one of interesting research. This research contains human feeling to computer application Such as the interaction between human and computer, data compression, facial animation and facial detection from the video. The purpose of this research is to create facial expression system that captures image from the video camera. The system in this research uses Widrow-Hoff learning method in training and testing image with Adaptive Linear Neuron (ADALINE) approach. The system performance is evaluated by two parameters, detection rate and false positive rate. The system accuracy depends on good technique and face position that trained and tested.

Methylation of Werner syndrome protein is associated with the occurrence and development of invasive meningioma via the regulation of Myc and p53 expression.

PubMed

Li, Puxian; Hao, Shuyu; Bi, Zhiyong; Zhang, Junting; Wu, Zhen; Ren, Xiaohui

2015-08-01

The aim of the present study was to investigate the positive rate of Werner syndrome protein (WRN) methylation in meningioma patients, and further assess the association between WRN methylation and the occurrence of meningioma. A total of 56 consecutive meningioma patients and 26 healthy individuals were enrolled in the study. A methylation-specific polymerase chain reaction assay was performed to detect the positive rate of WRN methylation in the peripheral blood and tissue samples collected from the recruited subjects. In addition, western blot analysis was performed to determine the protein expression levels of WRN, Myc and p53 in the peripheral blood and tissue samples. The positive rate of WRN methylation in the peripheral blood of the meningioma group was increased when compared with the control group (P<0.05). In addition, the protein expression levels of WRN were significantly decreased in the peripheral blood and tissue samples collected from the individuals with a positive WRN methylation status (P<0.05), as compared with the samples without WRN methylation. Furthermore, the protein expression levels of Myc and p53 were increased in the peripheral blood and tissue samples that exhibited positive WRN methylation when compared with those without WRN methylation (P<0.05). Therefore, WRN methylation was demonstrated to be associated with the occurrence and development of invasive meningioma, possibly through the regulation of Myc and p53 expression.

Cognitive "babyness": developmental differences in the power of young children's supernatural thinking to influence positive and negative affect.

PubMed

Periss, Virginia; Blasi, Carlos Hernández; Bjorklund, David F

2012-09-01

Perceptions of maturational status may play an important role in facilitating caretaking and resources toward children expressing them. Previous work has revealed evidence that cues of cognitive immaturity foster positive perceptions in adults toward young children at a time during their lives when they are most dependent on adult care. In the current series of studies, the authors investigated when during development these biases emerge. They tested American and Spanish adolescents ranging from 10 to 17 years of age. Each participant rated a series of vignettes presenting different expressions of immature and mature thinking attributed to young children. Results revealed that older adolescents performed similarly to adults tested in previous studies (D. F. Bjorklund, C. Hernández Blasi, & V. A. Periss, 2010), rating positively expressions of supernatural thinking (e.g., animism) compared with other forms of immature cognition labeled as natural (e.g., overestimation). Both male and female participants 14 years and older favored children expressing the immature supernatural cognition on traits reflecting positive affect (e.g., endearing, likeable), while associating greater negative affect (e.g., sneaky, impatient with) with children expressing immature natural cognition. However, younger adolescents consistently rated all forms of immature thinking less positively than mature thinking, suggesting that a positive bias for some forms of immature thinking develops during adolescence. Based on an evolutionary developmental framework, the authors suggest that supernatural thinking may have a unique role in humans, fostering positive perceptions of young children in older adolescents (and adults) as they prepare themselves for the possible role of parenthood. PsycINFO Database Record (c) 2012 APA, all rights reserved.

Expression of hypoxia-inducible 2 (HIG2) protein in uterine cancer.

PubMed

Nishimura, S; Tsuda, H; Nomura, H; Kataoka, F; Chiyoda, T; Tanaka, H; Tanaka, K; Susumu, N; Aoki, D

2011-01-01

For both cervical cancer (UCC) and endometrial cancer (EMC) there are no effective prognostic markers. In this study, we evaluated HIG2 protein expression in 332 uterine cancers (186 UCCs and 146 EMCs) and examined the relationship between HIG2 protein expression and clinical factors, including prognosis. Totally, HIG2 expression was detected in 58% of UCC and 66% of EMC. However, there was no significant relationship between HIG2 expression and age, clinical stage and histology in either UCC or EMC. In addition, HIG2 protein expression was not related to prognosis of UCC or EMC. The positivity rate of HIG2 protein was 56% and 61% in early-stage UCC and EMC, respectively and 67% in non-squamous cell carcinoma of UCC. The positivity rate of HIG2 protein was high even in early-stage UCC and EMC

Immunohistochemical study of mucins in human intestinal spirochetosis.

PubMed

Ogata, Sho; Shimizu, Ken; Tominaga, Susumu; Nakanishi, Kuniaki

2017-04-01

Most patients with human intestinal spirochetosis (HIS; a colorectal bacterial infection caused by Brachyspira species) seem asymptomatic, and its pathogenicity remains unclear. Recently, alterations in mucin expression were reported in animal Brachyspira infection. The present question was "Is mucin expression altered in HIS?" Using antibodies for MUCs 1, 2, 4, 5AC, and 6, we immunohistochemically compared 215 specimens from 83 histology-confirmed HIS cases with 106 specimens from 26 non-HIS cases. Positive staining (which included even focal positive staining) was rated "high (+)" or "low (+)." Results were analyzed for 4 categories of lesions, and associations between MUC expression and spirochetal presence were also analyzed. In the "specimens without polyps or adenocarcinoma" category, high (+) MUC2 positivity was more frequent in HIS than in control. In the hyperplasia/serrated polyp category, in HIS (versus control), the MUC5AC positivity rate was lower, whereas high (+) MUC4 positivity was more frequent. In the conventional adenoma category, in HIS (versus control), the MUC1 positivity rate was lower, whereas both high (+) MUC2 positivity and high (+) MUC5AC positivity were less frequent. In the adenocarcinoma category, high (+) MUC2 positivity was more frequent in HIS than in control. Among the above mucins, only MUC1 positivity was significantly associated with an absence of the so-called fringe formation, an absence of spiral organisms within mucus, and an absence of strong immunopositive materials within the epithelial layer and within the subepithelial layer. The results suggest that Brachyspira infection or a related change in the microbiome may alter the large intestine mucin expression profile in humans. Copyright © 2017 Elsevier Inc. All rights reserved.

Epac1, PDE4, and PKC protein expression and their association with AKAP95, Cx43, and cyclinD2/E1 in breast cancer tissues.

PubMed

Huang, Ping; Sun, Qian; Zhuang, Wenxin; Peng, Kuan; Wang, Dai; Yao, Youliang; Guo, Dongbei; Zhang, Lu; Shen, Chuhan; Sun, Mengyun; Tang, Chaoying; Teng, Bogang; Zhang, Yongxing

2017-09-01

This study was conducted to investigate the exchange protein directly activated by cAMP (Epac1), PDE4, and PKC expression in breast cancer tissues, and the correlation between these proteins and AKAP95, Cx43, cyclin D2, and cyclin E1. PV-9000 two-step immunohistochemistry was used to analyze protein expression. The positive rate of Epac1 protein expression in breast cancer tissues (58%) was higher than in para-carcinoma tissues (10%) (P < 0.05). There were no significant differences in the positive rates of PDE4 and PKC expression between breast cancer and para-carcinoma tissues (P > 0.05). The positive expression rate of PDE4 was higher in the P53 protein positive group compared to the P53 negative group (P < 0.05). Correlations between Epac1 and cyclin D2, PDE4 and cyclin D2, AKAP95 and PKC, Cx43 and PKC, and cyclin D2 and PKC proteins were observed (P < 0.05). Epac1 expression in breast cancer tissues was increased, suggesting that the protein may be involved in the development of breast cancer. Correlations between Epac1 and cyclin D2, PDE4 and cyclin D2, AKAP95 and PKC, Cx43 and PKC, and cyclin D2 and PKC proteins suggested synergistic effects among these proteins in the development of breast cancer. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Interpreting infant emotional expressions: Parenthood has differential effects on men and women.

PubMed

Parsons, Christine E; Young, Katherine S; Jegindoe Elmholdt, Else-Marie; Stein, Alan; Kringelbach, Morten L

2017-03-01

Interpreting and responding to an infant's emotional cues is a fundamental parenting skill. Responsivity to infant cues is frequently disrupted in depression, impacting negatively on child outcomes, which underscores its importance. It is widely assumed that women, and in particular mothers, show greater attunement to infants than do men. However, empirical evidence for sex and parental status effects, particularly in relation to perception of infant emotion, has been lacking. In this study, men and women with and without young infants were asked to rate valence in a range of infant facial expressions, on a scale of very positive to very negative. Results suggested complex interaction effects between parental status, sex, and the facial expression being rated. Mothers provided more positive ratings of the happy expressions and more extreme ratings of the intense emotion expressions than fathers, but non-mothers and non-fathers did not. Low-level depressive symptoms were also found to correlate with more negative ratings of negative infant facial expressions across the entire sample. Overall, these results suggest that parental status might have differential effects on men and women's appraisal of infant cues. Differences between fathers' and mothers' perceptions of infant emotion might be of interest in understanding variance in interaction styles, such as proportion of time spent in play.

Expression of NF-κB and PTEN in osteosarcoma and its clinical significance

PubMed Central

Gong, Teng; Su, Xuetao; Xia, Qun; Wang, Jinggui; Kan, Shilian

2017-01-01

We investigated the role of nuclear factor-κB (NF-κB) and phosphatase and tensin homolog deleted in chromosome 10 (PTEN) in the pathogenesis of osteosarcoma and its relationship with prognosis. Immunohistochemical method was used to detect the expression of NF-κB and PTEN in osteosarcoma and adjacent tissues. RT-PCR was used to detect the expression of NF-κB and PTEN mRNA in osteosarcoma and adjacent tissues. Western blotting was used to detect the expression of NF-κB and PTEN in osteosarcoma and adjacent tissues and compare their differences. The expression of NF-κB and PTEN was detected in osteosarcoma and adjacent tissues. The positive rate of NF-κB was 75.3 and 32.9%, respectively; while the positive rate of PTEN was 67.1 and 90.4%, respectively. The positive expression of NF-κB and PTEN was statistically significant. There was a negative correlation between NF-κB and PTEN expression (r=−0.502, p<0.05). The positive and negative expression of NF-κB and PTEN was statistically significant for the five-year survival (p<0.05). At gene and protein level, osteosarcoma tissues had higher expression of NF-κB, and lower expression of PTEN, which was significantly different from the adjacent tissues. In osteosarcoma, NF-κB is highly expressed, but PTEN is expressed at low level, and the two are negatively correlated. This is of great significance for the early diagnosis of osteosarcoma and prognosis. PMID:29151913

Expression of the Nrf2 and Keap1 proteins and their clinical significance in osteosarcoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Jihong, E-mail: zhangjihong63@163.com; Wang, Xiaojuan, E-mail: yangjian142@163.com; Wu, Wuzhou, E-mail: jiangchunli68@163.com

Objective: To investigate the expression and clinical significance of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) in osteosarcoma tissue. Methods: The data of 102 osteosarcoma patients who underwent surgical treatment at our hospital from June 2000 to March 2009 were collected. The expression levels of the Nrf2 and Keap1 proteins in osteosarcoma tissue and normal peritumour tissues were detected by immunohistochemistry, and the relationship between the expression level and the clinical and pathological features as well as the prognosis was explored. Results: The nuclear expression rate of Nrf2 was 77.5% in osteosarcoma tissue, which wasmore » significantly higher than the rate in normal peritumour bone tissue (9.8%) (P < 0.05). The expression rate of the Keap1 protein in osteosarcoma tissue was 13.7%, which was significantly lower than the rate in normal peritumour tissue (80.4%). In addition, Nrf2/Keap1 expression was unrelated to patient gender and age, tumour site, and histological type and was related to metastasis and patient response to chemotherapy (P < 0.05). The five-year survival rate was significantly lower in patients with positive Nrf2 expression than in those with negative Nrf2 expression (p = 0.023), and it was significantly higher in patients with positive Keap1 expression than in those with negative Keap1 expression (P = 0.018). Conclusion: The expression of Nrf2-Keap1 is abnormal in osteosarcoma tissue and shows significant clinical relevance for determining the prognosis of osteosarcoma.« less

Self-Expression on Social Media: Do Tweets Present Accurate and Positive Portraits of Impulsivity, Self-Esteem, and Attachment Style?

PubMed

Orehek, Edward; Human, Lauren J

2017-01-01

Self-expression values are at an all-time high, and people are increasingly relying upon social media platforms to express themselves positively and accurately. We examined whether self-expression on the social media platform Twitter elicits positive and accurate social perceptions. Eleven perceivers rated 128 individuals (targets; total dyadic impressions = 1,408) on their impulsivity, self-esteem, and attachment style, based solely on the information provided in targets' 10 most recent tweets. Targets were on average perceived normatively and with distinctive self-other agreement, indicating both positive and accurate social perceptions. There were also individual differences in how positively and accurately targets were perceived, which exploratory analyses indicated may be partially driven by differential word usage, such as the use of positive emotion words and self- versus other-focus. This study demonstrates that self-expression on social media can elicit both positive and accurate perceptions and begins to shed light on how to curate such perceptions.

CXCL14 and NOS1 expression in specimens from patients with stage I-IIIA nonsmall cell lung cancer after curative resection.

PubMed

Ji, Xiaoqin; Shen, Zetian; Zhao, Benxin; Yuan, Xi; Zhu, Xixu

2018-03-01

Many studies show that CXC chemokine ligand 14 (CXCL14) is highly expressed in tumor-associated stromal cells, promoting tumor cell growth, and invasion. Because of its unclear receptors, CXCL14-initiated intracellular signal cascades remain largely unknown. However, CXCL14 can regulate nitric oxide synthase 1 (NOS1) as its intracellular molecular target. In this paper, we investigated the expression of CXCL14 and NOS1 in specimens from patients with stage I-IIIA nonsmall cell lung cancer (NSCLC) after curative resection, and evaluated the prognostic significance of this gene expression in stromal fibroblasts and cancer cells.Immunohistochemistry was used to detect the expression of CXCL14 and NOS1 in 106 formalin fixed, paraffin-embedded specimens from patients with stage I-IIIA NSCLC. The chi-square test was performed to examine the correlation of CXCL14 and NOS1 expression level with clinicopathological features. The effects of the expression of CXCL14 or NOS1 on progression-free survival (PFS) and overall survival (OS) were determined by Kaplan-Meier and Cox hazard proportional model.The percentages of high CXCL14 expression in stromal fibroblasts and that in cancer cells were 46.2% (49/106) and 23.6% (25/106), respectively. The positive expression rates of NOS1 in cancer cells were 42.5% (45/106). The result indicated that there was a significant positive correlation between CXCL14 expression level in stromal fibroblasts and that in cancer cells (χ = 4.158, P = .041). In addition, the expression of CXCL14 in stromal fibroblasts was significantly correlated with NOS1 expression in cancer cells (χ = 16.156, P < .001). The 5-year PFS rates with low and high CXCL14 expression in stromal fibroblasts were 66.7% and 14.3% (χ = 44.008, P < .001), respectively, and the 5-year OS rates with those were 87.1% and 43.5% (χ = 21.531, P < .001), respectively. The 5-year PFS rates with negative and positive expression of NOS1 in cancer cells were 62.3% and 15.6% (χ = 33.756, P < .001), respectively, and the 5-year OS rates with those were 86.4% and 40.1% (χ = 24.430, P < 0.01), respectively.Both the high expression of CXCL14 in stromal fibroblasts and the positive expression of NOS1 in cancer cells are independent negative predictors of PFS and OS in patients with stage I-IIIA NSCLC after curative resection.

Differential cyclooxygenase-2 expression in squamous cell carcinoma and adenocarcinoma of the uterine cervix.

PubMed

Kim, Yong Bae; Kim, Gwi Eon; Pyo, Hong Ryull; Cho, Nam Hoon; Keum, Ki Chang; Lee, Chang Geol; Seong, Jinsil; Suh, Chang Ok; Park, Tchan Kyu

2004-11-01

To determine the differential expression of cyclooxygenase-2 (COX-2) in patients with squamous cell carcinoma (SCC) and adenocarcinoma (ADC) of the uterine cervix and the prognostic significance of COX-2 expression in these histologic types. A total of 105 International Federation of Gynecology and Obstetrics Stage IIB uterine cervical cancer patients were screened for COX-2 expression immunohistochemically. COX-2 expression was determined in invasive cervical SCC (n = 84) and invasive cervical ADC (n = 21). To determine the clinical significance of COX-2 expression by histologic type, the patients were arbitrarily divided into four groups: SCC/COX-2 negative (n = 64); SCC/COX-2 positive (n = 20); ADC/COX-2 negative (n = 9); and ADC/COX-2 positive (n = 12). The clinical response to treatment, patterns of treatment failure, and survival data by COX-2 expression were compared for these two major histologic types. Univariate and multivariate analyses were performed to identify the prognostic factors influencing survival. Immunohistochemical examination showed that COX-2 expression was more frequently observed in ADC than in SCC (57% vs. 24%, p = 0.007). Moreover, COX-2 expression was an important predictor of treatment response, irrespective of the histologic type. All COX-2-negative patients achieved complete remission after initial treatment; 17% of SCC patients and 33% of ADC patients with COX-2 expression did not have complete remission after the initial treatment. The incidence of local failure for those with COX-2 expression was significantly greater than for COX-2-negative patients, regardless of histologic type. With a minimal follow-up of 60 months, the overall 5-year actuarial survival rate for SCC and ADC patients was 79% and 62%, respectively (p = 0.05). The 5-year disease-free survival rate for SCC and ADC patients was 73% and 56%, respectively (p = 0.13). Irrespective of the pathologic type, COX-2-positive patients had an unfavorable prognosis. The overall 5-year actuarial survival rate was 57% for COX-2-positive patients and 83% for COX-2-negative patients (p = 0.001). When patients were stratified into the four groups according to histologic type and COX-2 expression status, ADC/COX-2-positive patients had the worst prognosis, with an overall 5-year actuarial survival rate of 49% compared with 78% for ADC/COX-2-negative patients, 62% for SCC/COX-2-positive, and 84% for SCC/COX-2-negative patients (p = 0.007, log-rank test). Irrespective of histologic type, COX-2 expression was an independent prognostic factor by univariate and multivariate analyses. In uterine cervical cancer, COX-2 was expressed in a greater proportion of ADC patients than SCC patients. COX-2 expression was also identified as a major determiner of a poor response to treatment and of an unfavorable prognosis, irrespective of the histologic type, reflecting the importance of the COX-2 protein in the acquisition of biologic aggressiveness and more malignant phenotype or increased resistance to the standard chemotherapy and radiotherapy in both histologic types. Given these observations, we believe that that ADC/COX-2-positive patients might be appropriate candidates for future trials of selective COX-2 inhibitor adjunctive therapy.

[Correlation between bacterial L-form infection, expression of HIF-1α/MMP-9 and vasculogenic mimicry in epithelial ovarian cancer].

PubMed

Yu, Lan; Wu, Shi-Wu; Zhou, Lei; Song, Wen-Qing

2012-12-25

The aim of the present study is to explore whether vasculogenic mimicry (VM) and bacterial L-form infection exist in human epithelial ovarian cancer (EOC) or not and to elucidate the correlation of L-form infection, expression of hypoxia inducible factor 1α (HIF-1α)/MMP-9 and VM. In 87 specimens of EOC and 20 specimens of ovarian benign epithelial tumor tissues, L-form infection was detected by Gram's staining, expression of HIF-1α/MMP-9 and VM were detected by immunohistochemical and histochemical staining. The results showed that the positive rates of HIF-1α and MMP-9 protein in EOC were 52.9% and 66.7%, while in benign epithelial tumor tissues, the positive rates were 10.0% and 10.0% respectively, and there were significant differences between them (P < 0.05). In EOC and benign epithelial tumor tissues, L-form infections ratios were 24.1% and 0, respectively, and the difference was also significant (P < 0.01). Expression of VM, HIF-1α and MMP-9 in EOC was significantly related to differentiation, abdominal implantation and lymph node metastasis and FIGO stage (P < 0.01). L-form infection had relationship with abdominal implantation, lymph node metastasis and FIGO stage (P < 0.01 or 0.05). The expression of HIF-1α had positive relationship with expression of MMP-9 and VM (r = 0.505, 0.585, respectively, P < 0.01); there was also a positive relationship between MMP-9 expression and VM (r = 0.625, P < 0.01). Overexpression of VM, HIF-1α and MMP-9 were related to poor prognosis: the survival rates were significantly lower in positive patients than those in negative patients (P < 0.05). And the group with L-form infection also had poor prognosis: the survival rates were lower than those in group without infection (P < 0.05). FIGO stage, expression of VM, HIF-1α and MMP-9 were independent prognosis factors of EOC (P < 0.05). The results suggest that L-form infection, the expression of HIF-1α, MMP-9 and VM in EOC are related to differentiation, lymph node metastasis, clinical stage and prognosis. Combined detection of these indexes has an important role in predicting the progression and prognosis of EOC.

Positive Selection Underlies Faster-Z Evolution of Gene Expression in Birds.

PubMed

Dean, Rebecca; Harrison, Peter W; Wright, Alison E; Zimmer, Fabian; Mank, Judith E

2015-10-01

The elevated rate of evolution for genes on sex chromosomes compared with autosomes (Fast-X or Fast-Z evolution) can result either from positive selection in the heterogametic sex or from nonadaptive consequences of reduced relative effective population size. Recent work in birds suggests that Fast-Z of coding sequence is primarily due to relaxed purifying selection resulting from reduced relative effective population size. However, gene sequence and gene expression are often subject to distinct evolutionary pressures; therefore, we tested for Fast-Z in gene expression using next-generation RNA-sequencing data from multiple avian species. Similar to studies of Fast-Z in coding sequence, we recover clear signatures of Fast-Z in gene expression; however, in contrast to coding sequence, our data indicate that Fast-Z in expression is due to positive selection acting primarily in females. In the soma, where gene expression is highly correlated between the sexes, we detected Fast-Z in both sexes, although at a higher rate in females, suggesting that many positively selected expression changes in females are also expressed in males. In the gonad, where intersexual correlations in expression are much lower, we detected Fast-Z for female gene expression, but crucially, not males. This suggests that a large amount of expression variation is sex-specific in its effects within the gonad. Taken together, our results indicate that Fast-Z evolution of gene expression is the product of positive selection acting on recessive beneficial alleles in the heterogametic sex. More broadly, our analysis suggests that the adaptive potential of Z chromosome gene expression may be much greater than that of gene sequence, results which have important implications for the role of sex chromosomes in speciation and sexual selection. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

The specific social costs of expressive negative symptoms in schizophrenia: reduced smiling predicts interactional outcome.

PubMed

Riehle, M; Mehl, S; Lincoln, T M

2018-04-17

We tested whether people with schizophrenia and prominent expressive negative symptoms (ENS) show reduced facial expressions in face-to-face social interactions and whether this expressive reduction explains negative social evaluations of these persons. We compared participants with schizophrenia with high ENS (n = 18) with participants with schizophrenia with low ENS (n = 30) and with healthy controls (n = 39). Participants engaged in an affiliative role-play that was coded for the frequency of positive and negative facial expression and rated for social performance skills and willingness for future interactions with the respective role-play partner. Participants with schizophrenia with high ENS showed significantly fewer positive facial expressions than those with low ENS and controls and were also rated significantly lower on social performance skills and willingness for future interactions. Participants with schizophrenia with low ENS did not differ from controls on these measures. The group difference in willingness for future interactions was significantly and independently mediated by the reduced positive facial expressions and social performance skills. Reduced facial expressiveness in schizophrenia is specifically related to ENS and has negative social consequences. These findings highlight the need to develop aetiological models and targeted interventions for ENS and its social consequences. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Expression of connective tissue growth factor in colorectal cancer and its association with prognosis].

PubMed

Sun, Zheng; Yang, Ping; Liang, Li-yuan; Zhang, Tong; Zhang, Wei-jian; Cao, Jie

2012-11-01

To investigate the expression of connective tissue growth factor (CTGF) in colorectal cancer(CRC) and its association with clinicopathologic parameters and overall survival rate. Fresh tumor tissues and matched distal normal colon tissues were collected from 92 patients diagnosed as CRC by surgical operation. The expression level of CTGF mRNA was quantified by quantitative reverse transcription PCR. Thirty out of 92 pairs of tissue specimens were selected randomly to detect CTGF protein by immunohistochemistry. All the cases were followed up to identify prognostic factors for survival. CTGF mRNA expression was up-regulated in CRC. The positive rate of CTGF protein expression tissues (73.3%) was significantly higher than that in the corresponding normal tissues (23.3%, P<0.01). CTGF expression was lower in patients with lymphatic metastasis or stage III/IIII disease (all P<0.05). A negative association was also observed between the CTGF protein positive rate and tumor infiltration depth (P<0.05). The relative expression of CTGF mRNA in tumor tissues was classified into high and low expression groups. The 5-year cumulative survival rate was lower in patients with low CTGF expression (29.3%) as compared to those with high CTGF expressions (68.3%) (P<0.01). Cox regression analysis revealed that the relative expression level of CTGF was independent factor of overall survival (RR=2.960, 95%CI:1.491-1.587, P<0.01). ROC curve analysis showed that sensitivity and specificity of CTGF mRNA expression for prediction of 5-year survival were 64.9% and 74.5%, respectively. The aberrant expression of CTGF is associated with the malignant biological behaviors of CRC. Low expression of CTGF is associated with worse prognosis of CRC.

[Analysis of expression of cancer stem cell-related markers in orbital adenoid cystic carcinoma].

PubMed

Lin, Ting-ting; Zhu, Li-min; He, Yan-jin; Zhang, Hong

2011-08-01

To observe the expression and distribution of CD44, CD133, and ABCG2 in orbital adenoid cystic carcinoma (ACC) and investigate their correlations with pathological type and prognosis. Two steps method of immunohistochemical staining was employed in 33 cases of paraffin embedded surgical specimens of human orbital ACC, 5 cases of recurrence samples, 3 cases of an excised lacrimal gland caused by neither inflammation nor tumor diseases, and 6 cases of xenograft tumors in nude mice. A retrospective analysis was performed on the clinical material of these patients, which were collected from Jan. 1991 to Mar. 2009. The positive rate of CD44 was 54.5% (18/33), with 76.9% (10/13) in solid type and 40.0% (8/20) in adeno-tubiform type. There was no statistically significant difference between them (P = 0.072). In solid type the positive expression cells were often located at the marginal part of the cancer nest. In the adeno-tubiform type, positive cells were often located at the outer layer of the tubiform structure (myoepithelial cells). CD44 was also expressed in normal tissues. The positive rate of CD133 was 57.6% (19/33), with 76.9% (10/13) in solid type and 45.0% (9/20) in adeno-tubiform type. There was no significant difference between them (P = 0.087). CD133 antigen was expressed in either the cytoplasm or nucleus, or expressed in both the cytoplasm and nucleus. The positive rate of ABCG2 was 21.2% (7/33), with 30.77% (4/13) in solid type and 15.0% (3/20) in adeno-tubiform type. There was no significant difference between them (P = 0.393). Many positive cells surrounded the vessels in tumor tissues. There were no significant differences between different prognosis groups of these surface phenotypes. The correlative analysis results of three surface phenotypes showed that CD44(+) cells have positive correlation with CD133(+) cells (Spearman, r(s) = 0.416, P = 0.016). In six transplanted tumors of nude mice, the number of positive cases for CD44(+), CD133(+) and ABCG2(+) was 1, 1 and 4 cases, respectively. The expression of CD44, CD133 and ABCG2 in ACC may influence the progress of ACC. However, they cannot be used as the markers for the evaluation of the prognosis of this tumor.

Clinicopathological significance of c-MYC in esophageal squamous cell carcinoma.

PubMed

Lian, Yu; Niu, Xiangdong; Cai, Hui; Yang, Xiaojun; Ma, Haizhong; Ma, Shixun; Zhang, Yupeng; Chen, Yifeng

2017-07-01

Esophageal squamous cell carcinoma is one of the most common malignant tumors. The oncogene c-MYC is thought to be important in the initiation, promotion, and therapy resistance of cancer. In this study, we aim to investigate the clinicopathologic roles of c-MYC in esophageal squamous cell carcinoma tissue. This study is aimed at discovering and analyzing c-MYC expression in a series of human esophageal tissues. A total of 95 esophageal squamous cell carcinoma samples were analyzed by the western blotting and immunohistochemistry techniques. Then, correlation of c-MYC expression with clinicopathological features of esophageal squamous cell carcinoma patients was statistically analyzed. In most esophageal squamous cell carcinoma cases, the c-MYC expression was positive in tumor tissues. The positive rate of c-MYC expression in tumor tissues was 61.05%, obviously higher than the adjacent normal tissues (8.42%, 8/92) and atypical hyperplasia tissues (19.75%, 16/95). There was a statistical difference among adjacent normal tissues, atypical hyperplasia tissues, and tumor tissues. Overexpression of the c-MYC was detected in 61.05% (58/95) esophageal squamous cell carcinomas, which was significantly correlated with the degree of differentiation (p = 0.004). The positive rate of c-MYC expression was 40.0% in well-differentiated esophageal tissues, with a significantly statistical difference (p = 0.004). The positive rate of c-MYC was 41.5% in T1 + T2 esophageal tissues and 74.1% in T3 + T4 esophageal tissues, with a significantly statistical difference (p = 0.001). The positive rate of c-MYC was 45.0% in I + II esophageal tissues and 72.2% in III + IV esophageal tissues, with a significantly statistical difference (p = 0.011). The c-MYC expression strongly correlated with clinical staging (p = 0.011), differentiation degree (p = 0.004), lymph node metastasis (p = 0.003), and invasion depth (p = 0.001) of patients with esophageal squamous cell carcinoma. The c-MYC was differentially expressed in a series of human esophageal tissues, and the aberrant c-MYC expression could be a potential factor in carcinogenesis and progression of esophageal squamous cell carcinoma. There was a statistical signification for c-MYC in esophageal squamous cell carcinoma patients to analyze clinicopathological features. It possibly becomes a new diagnostic indicator of esophageal squamous cell carcinoma.

Correlation of SASH1 expression and ultrasonographic features in breast cancer.

PubMed

Gong, Xuchu; Wu, Jinna; Wu, Jian; Liu, Jun; Gu, Hailin; Shen, Hao

2017-01-01

SASH1 is a member of the SH3/SAM adapter molecules family and has been identified as a new tumor suppressor and critical protein in signal transduction. An ectopic expression of SASH1 is associated with decreased cell viability of breast cancer. The aim of this study was to explore the association between SASH1 expression and the ultrasonographic features in breast cancer. A total of 186 patients diagnosed with breast cancer were included in this study. The patients received preoperative ultrasound examination, and the expression of SASH1 was determined using immunohistochemistry methods. Spearman's rank correlation analysis was used to analyze the correlation between SASH1-positive expression and the ultrasonographic features. The positive expression of SASH1 was observed in 63 (33.9%) patients. The positive expression rate of SASH1 was significantly decreased in patients with breast cancer (63/186, 33.9%) compared with controls ( P <0.001). The positive expression rate of SASH1 was significantly decreased in patients with edge burr sign ( P =0.025), lymph node metastasis ( P =0.007), and a blood flow grade of III ( P =0.013) compared with patients without those adverse ultrasonographic features. The expression of SASH1 was negatively correlated with edge burr sign ( P =0.025), lymph node metastasis ( P =0.007), and blood flow grade ( P =0.003) of the patients with breast cancer. The expression of SASH1 was inversely correlated with some critical ultrasonographic features, including edge burr sign, lymph node metastasis, and blood flow grade in breast cancer, and decreased SASH1 expression appears to be associated with adverse clinical and imaging features in breast cancer.

Correlation of SASH1 expression and ultrasonographic features in breast cancer

PubMed Central

Gong, Xuchu; Wu, Jinna; Wu, Jian; Liu, Jun; Gu, Hailin; Shen, Hao

2017-01-01

Objective SASH1 is a member of the SH3/SAM adapter molecules family and has been identified as a new tumor suppressor and critical protein in signal transduction. An ectopic expression of SASH1 is associated with decreased cell viability of breast cancer. The aim of this study was to explore the association between SASH1 expression and the ultrasonographic features in breast cancer. Patients and methods A total of 186 patients diagnosed with breast cancer were included in this study. The patients received preoperative ultrasound examination, and the expression of SASH1 was determined using immunohistochemistry methods. Spearman’s rank correlation analysis was used to analyze the correlation between SASH1-positive expression and the ultrasonographic features. Results The positive expression of SASH1 was observed in 63 (33.9%) patients. The positive expression rate of SASH1 was significantly decreased in patients with breast cancer (63/186, 33.9%) compared with controls (P<0.001). The positive expression rate of SASH1 was significantly decreased in patients with edge burr sign (P=0.025), lymph node metastasis (P=0.007), and a blood flow grade of III (P=0.013) compared with patients without those adverse ultrasonographic features. The expression of SASH1 was negatively correlated with edge burr sign (P=0.025), lymph node metastasis (P=0.007), and blood flow grade (P=0.003) of the patients with breast cancer. Conclusion The expression of SASH1 was inversely correlated with some critical ultrasonographic features, including edge burr sign, lymph node metastasis, and blood flow grade in breast cancer, and decreased SASH1 expression appears to be associated with adverse clinical and imaging features in breast cancer. PMID:28138250

[Correlation of CD82 and hTERT expressions and HPV infection with penile cancer].

PubMed

Zhai, Jian-Po; Li, Ming; Wang, Qi-Yan; Wei, Dong; Xu, Ke-Xin

2011-09-01

To study the correlation of the expressions of CD82 and hTERT and HPV infection with the clinical pathological features of penile cancer and identify their prognostic significance in the lymphatic metastasis of the disease. A total of 44 patients underwent partial or radical penectomy and lymph node dissection. The expressions of CD82 and hTERT were determined by immunohistochemistry, and HPV infection was detected by PCR. The positive rates of CD82, hTERT, and HPV DNA in penile carcinoma were 47.7%, 38.6% and 25.9%, respectively. The amplified HPV DNA was HPV-16. The pathological stage and hTERT expression were positively correlated with inguinal lymph node metastasis of penile cancer (P = 0.032, P = 0.041), and so was the pathological stage with the expression of CD82 (P = 0.045), but neither the pathological stage, nor the expression of CD82 or the positive rate of HPV DNA showed any correlation with lymph node metastasis (P = 0.627, P = 0.094, P = 0.633). The pathological grade and hTERT expression are independent prognostic factors for lymph node metastasis in penile carcinoma. These features help the prognosis and identification of the patient at the risk of nodal metastasis.

Expression and significance of molecular biomarkers in esophageal carcinoma in different nationalities patients in Xinjiang.

PubMed

Zhang, L; Sun, J; Zhang, J Q; Yang, M; Bai, G; Ma, X L

2014-07-24

This study aimed to explore some useful biomarkers to focus on the diagnosis and therapy response judgment in esophageal squamous cell carcinoma in Xinjiang. We used enzyme-linked immunosorbent method and immunohistochemistry to detect the expression of VEGF, EGFR, ES, HER-2, and NF-κBp in the serum and tissue with esophageal squamous cell carcinoma, and to analyze the relationship between biomarkers and clinical pathology and curative effects. Our findings were as follows: 1. The serum levels of VEGF and ES in Han patients were obviously higher than those of Uygur and Kazakh patients (P < 0.05). The VEGF positive rate in patients at a later clinical stage was higher than that of the patients at an earlier clinical stage (stages II-IV were 14.29, 50.00, and 50.00%, respectively, P < 0.05), meanwhile it was higher than that of patients without lymph node metastases (78.13 vs 25.00%, P < 0.05). The curative effective rate of patients with negative expression of VEGF was higher than that of patients with positive expression of VEGF (74.67 vs 41.40%, P < 0.05). 2. The expression of EGFR protein in male patients was higher than that of female patients (69.77 vs 35.29%, P < 0.05). Before treatment, the serum EGFR level in patients was higher than the normal group (P < 0.05). 3. The serum ES level in patients before and after treatment was significantly higher than in the normal group (P < 0.05). 4. The HER-2 positive rate in higher differentiated tumor tissue was lower than that in lower differentiated tumor tissue. (The positive rate of I, II, III grade was 70.00, 30.00, and 20.00%, respectively, P < 0.05). 5. The NF-κB positive rate in patients with lymph node metastases was higher than that of patients without lymph node metastases (65.63 vs 39.27%, P < 0.05), meanwhile median survival in the latter group was higher than that of the former group (P < 0.05). Our data suggest that the expression of VEGF and ES were different in Uygur, Han, and Kazakh patients in Xinjiang. The combined detection of tumor markers in serum and tissue is of direct significance for tumor therapy.

The expression of β-galactosidase during long-term cultured goat skin fibroblasts and the effect of donor cell passage on in vitro development of nuclear transfer embryos.

PubMed

Liu, Haijun; Peng, Hui; Liu, Fang; Ma, Qun; Zhang, Wenchang

2016-05-01

The present study aimed to detect the expression of β-galactosidase during long-term cultured goat skin fibroblasts and investigate the effects of donor goat age, sex, and cell passage on senescence and the effects of donor cell passage on in vitro development of nuclear transfer embryos. The results showed that, in the same cell passage, more β-galactosidase-positive cells were detected in cells from older donors than younger donors. Irrespective of the donor age, the number of positive cells was higher in later passages from passages 20 to 50. In the same passage from 20 to 50, the β-galactosidase-positive rate was higher in cells from 5-yr female goat than 5-yr male goat. Using fibroblasts from male goats at various passages as donor cells, reconstructed embryos had similar fusion and cleavage rates, but the blastocyst rate was higher for cells at passages 10 and 20 than passage 30. In conclusion, donor goat age and cell passage had significant effects on the β-galactosidase-positive rate; also, cells from 5-yr female goat had a higher β-galactosidase-positive rate than those from 5-yr male goat, and the donor cell passage affected the developmental potential of nuclear transfer embryos.

[Expression and Significance of PI-PLCε1 in Colon Cancer].

PubMed

Li, Xiao-Ran; Yang, Kun; Huang, Xiao-Li

2017-11-01

To study the expression and clinical significance of phosphoinositide-specific phospholipase Cε1 (PI-PLCε1) in the pathogenesis of colon cancer. qRT-PCR and immunohistochemistry were used to detect the expression of PI-PLCε1 in the 42 cases of colon cancer tissues and their corresponding adjacent tissues. And the effects of tumor differentiation and tumor site on the expression PI-PLCε1 of colon cancer tissues were compared. The results of qRT-PCR showed that the expression of PI-PLCε1 in colon cancer tissue significantly lower than that in the adjacent tissue ( P <0.05). The expression of PI-PLCε1 gene of colon cancer tissue was not effected by tumor differentiation and tumor site ( P >0.05). The results of immuno-histochemistry showed that the positive expression rate of PI-PLCε1 protein in colon cancer tissue was significantly lower than that in the adjacent tissue ( P <0.05). The positive expression rate of PI-PLCε1 protein was not effected by tumor differentiation ( P >0.05),but the expression was different in tumor site ( P <0.05). Expression of PI-PLCε1 was reduced in colon tissue and barely to tumor differentiation.

Positive empathy: a therapeutic skill inspired by positive psychology.

PubMed

Conoley, Collie W; Pontrelli, Marla E; Oromendia, Mercedes Fernández; Del Carmen Bello, Beatriz; Nagata, Chelsea M

2015-06-01

Positive empathy (PE), a type of empathy response that focuses on a client's hidden message of desire for a better life, was hypothesized to increase the expression of positive emotions, approach goals, and strengths, and to communicate equivalent understanding when compared to traditional empathy (TE). We examined 4 hypotheses in 2 studies. In study 1, college participants read therapy session vignettes incorporating PE or TE and then listed the client's strengths and goals and rated the therapist and how well they imagined themselves as the client in the vignettes. In study 2, therapist-client dyads attended 6 weekly sessions that incorporated both PE and TE, after which clients rated therapists' level of empathic understanding and session observers rated clients' emotional responses, revelations of strengths, and goals in response to empathy. In both studies, the results of PE and TE were similar, while PE elicited a greater number of approach goals. In study 2, clients expressed more strengths and positive emotions after PE responses than TE. Our results support PE for enhancing client growth (i.e., when a client pursues approach goals, enlists strengths, and experiences positive emotions), which is consistent with the process of positive psychology-informed psychotherapy. © 2015 Wiley Periodicals, Inc.

HPV infection and P16 expression in oral and oropharyngeal cancer in Kazakhstan.

PubMed

Adilbay, Dauren; Adilbayev, Galim; Kidirbayeva, Gulzhan; Shipilova, Viktoria; Sadyk, Zhanat; Koyanbekova, Gulsum; Sokolenko, Ekaterina; Klozar, Jan

2018-01-01

Human papillomavirus (HPV) is an important etiologic factor in different cancers of anogenital region and also in a fraction of head and neck cancers (HNC) particularly oropharyngeal tumors. The HPV16 genotype associated with the majority of HPV-related head and neck carcinomas. Th incidence of oropharyngeal cancer is increasing in many countries, and the rate of HPV positive tumors is about 70% in Europe and North America. Little known about the prevalence of HPV in HNC in Central Asia. It's a prospective analysis of patients with verified oral or oropharyngeal cancer. Sociodemographic and clinical data obtained on admission to treatment. The diagnosis of HPV positivity assessed by both the P16 expression on immunohistochemistry(IHC) and polymerase chain reaction (PCR)with HPV DNA detection and HR HPV type determination. Seventy six patients with oral and oropharyngeal cancer tested for HPV. Forteen cases were positive for HPV by PCR and 15 cases by P16 IHC. Of the 35 oropharyngeal tumors, nine were HPV DNA and p16 IHC positive, giving the rate of 25.7%. Of the 41 oral tumors, five were HPV DNA and six p16 IHC positive, giving the rate of 12.2%. It is the first study mapping prevalence of HPV positivity in oral and oropharyngeal cancer in the Central Asian region. The rate of HPV positivity was higher in oropharyngeal than in oral cancer, the nonsmokers were significantly more frequent in the HPV positive group and HPV 16 was the most frequent type. However, the HPV positivity rates are lower than referred in the western world.

Neural evidence for cultural differences in the valuation of positive facial expressions

PubMed Central

Park, BoKyung; Chim, Louise; Blevins, Elizabeth; Knutson, Brian

2016-01-01

European Americans value excitement more and calm less than Chinese. Within cultures, European Americans value excited and calm states similarly, whereas Chinese value calm more than excited states. To examine how these cultural differences influence people’s immediate responses to excited vs calm facial expressions, we combined a facial rating task with functional magnetic resonance imaging. During scanning, European American (n = 19) and Chinese (n = 19) females viewed and rated faces that varied by expression (excited, calm), ethnicity (White, Asian) and gender (male, female). As predicted, European Americans showed greater activity in circuits associated with affect and reward (bilateral ventral striatum, left caudate) while viewing excited vs calm expressions than did Chinese. Within cultures, European Americans responded to excited vs calm expressions similarly, whereas Chinese showed greater activity in these circuits in response to calm vs excited expressions regardless of targets’ ethnicity or gender. Across cultural groups, greater ventral striatal activity while viewing excited vs. calm expressions predicted greater preference for excited vs calm expressions months later. These findings provide neural evidence that people find viewing the specific positive facial expressions valued by their cultures to be rewarding and relevant. PMID:26342220

Relationship between expression of gastrin, somatostatin, Fas/FasL and caspases in large intestinal carcinoma.

PubMed

Mao, Jia-Ding; Wu, Pei; Yang, Ying-Lin; Wu, Jian; Huang, He

2008-05-14

To explore the correlation between the mRNAs and protein expression of gastrin (GAS), somatostatin (SS) and apoptosis index (AI), apoptosis regulation gene Fas/FasL and caspases in large intestinal carcinoma (LIC). Expression of GAS and SS mRNAs were detected by nested RT-PCR in 79 cases of LIC. Cell apoptosis was detected by molecular biology in situ apoptosis detecting methods (TUNEL). Immunohistochemical staining for GAS, SS, Fas/FasL, caspase-3 and caspase-8 was performed according to the standard streptavidin-biotin-peroxidase (S-P) method. There was a significant positive correlation between mRNA and protein expression of GAS and SS (GASrs = 0.99, P < 0.01; SSrs = 0.98, P < 0.01). There was significant difference in positive expression rates of GAS, SS mRNAs and protein among different histological differentiation, histological types and Dukes' stage of LIC. The AI in GAS high and moderate expression groups was significantly lower than that in low expression groups (3.75 +/- 2.38 vs 7.82 +/- 2.38, P < 0.01; 5.51 +/- 2.66 vs 7.82 +/- 2.38, P < 0.01), and the AI in SS high and moderate expression groups was significantly higher than that in low expression groups (9.03 +/- 1.76 vs 5.35 +/- 3.00, P < 0.01; 7.44 +/- 2.67 vs 5.35 +/- 3.00, P < 0.01). There was a significant negative correlation between the integral ratio of GAS to SS and the AI (r(s) = -0.41, P < 0.01). The positive expression rate of FasL in GAS high and moderate expression groups was higher than that in low expression group (90.9% and 81.0% vs 53.2%, P < 0.05). The positive expression rates of Fas, caspase-8 and caspase-3 in SS high (90.0%, 90.0% and 100%) and moderate (80.0%, 70.0%, 75.0%) expression groups were higher than that in low expression group (53.1%, 42.9%, 49.0%) (90.0% and 80.0% vs 53.1%, P < 0.05; 90.0% and 70.0% vs 42.9%, P < 0.05; 100.0% and 75.0% vs 49.0%, P < 0.05). There was a significant positive correlation between the integral ratio of GAS to SS and the semiquantitative integral of FasL (rs = 0.32, P < 0.01). GAS and SS play important roles in the regulation and control of cell apoptosis in LIC, and the mechanism may be directly related to the aberrant expression of Fas/FasL. The GAS and SS will be valuable targets of the biological behavior of LIC.

Relationship between expression of gastrin, somatostatin, Fas/FasL and caspases in large intestinal carcinoma

PubMed Central

Mao, Jia-Ding; Wu, Pei; Yang, Ying-Lin; Wu, Jian; Huang, He

2008-01-01

AIM: To explore the correlation between the mRNAs and protein expression of gastrin (GAS), somatostatin (SS) and apoptosis index (AI), apoptosis regulation gene Fas/FasL and caspases in large intestinal carcinoma (LIC). METHODS: Expression of GAS and SS mRNAs were detected by nested RT-PCR in 79 cases of LIC. Cell apoptosis was detected by molecular biology in situ apoptosis detecting methods (TUNEL). Immunohistochemical staining for GAS, SS, Fas/FasL, caspase-3 and caspase-8 was performed according to the standard streptavidin-biotin-peroxidase (S-P) method. RESULTS: There was a significant positive correlation between mRNA and protein expression of GAS and SS (GASrs=0.99, P < 0.01; SSrs = 0.98, P < 0.01). There was significant difference in positive expression rates of GAS, SS mRNAs and protein among different histological differentiation, histological types and Dukes’ stage of LIC. The AI in GAS high and moderate expression groups was significantly lower than that in low expression groups (3.75 ± 2.38 vs 7.82 ± 2.38, P < 0.01; 5.51 ± 2.66 vs 7.82 ± 2.38, P < 0.01), and the AI in SS high and moderate expression groups was significantly higher than that in low expression groups (9.03 ± 1.76 vs 5.35 ± 3.00, P < 0.01; 7.44 ± 2.67 vs 5.35 ± 3.00, P < 0.01). There was a significant negative correlation between the integral ratio of GAS to SS and the AI (rs = -0.41, P < 0.01). The positive expression rate of FasL in GAS high and moderate expression groups was higher than that in low expression group (90.9% and 81.0% vs 53.2%, P < 0.05). The positive expression rates of Fas, caspase-8 and caspase-3 in SS high (90.0%, 90.0% and 100%) and moderate (80.0%, 70.0%, 75.0%) expression groups were higher than that in low expression group (53.1%, 42.9%, 49.0%) (90.0% and 80.0% vs 53.1%, P < 0.05; 90.0% and 70.0% vs 42.9%, P < 0.05; 100.0% and 75.0% vs 49.0%, P < 0.05). There was a significant positive correlation between the integral ratio of GAS to SS and the semiquantitative integral of FasL (rs = 0.32, P < 0.01). CONCLUSION: GAS and SS play important roles in the regulation and control of cell apoptosis in LIC, and the mechanism may be directly related to the aberrant expression of Fas/FasL. The GAS and SS will be valuable targets of the biological behavior of LIC. PMID:18473402

Cultural Differences in Affect Intensity Perception in the Context of Advertising

PubMed Central

Pogosyan, Marianna; Engelmann, Jan B.

2011-01-01

Cultural differences in the perception of positive affect intensity within an advertising context were investigated among American, Japanese, and Russian participants. Participants were asked to rate the intensity of facial expressions of positive emotions, which displayed either subtle, low intensity, or salient, high intensity expressions of positive affect. In agreement with previous findings from cross-cultural psychological research, current results demonstrate both cross-cultural agreement and differences in the perception of positive affect intensity across the three cultures. Specifically, American participants perceived high arousal (HA) images as significantly less calm than participants from the other two cultures, while the Japanese participants perceived low arousal (LA) images as significantly more excited than participants from the other cultures. The underlying mechanisms of these cultural differences were further investigated through difference scores that probed for cultural differences in perception and categorization of positive emotions. Findings indicate that rating differences are due to (1) perceptual differences in the extent to which HA images were discriminated from LA images, and (2) categorization differences in the extent to which facial expressions were grouped into affect intensity categories. Specifically, American participants revealed significantly higher perceptual differentiation between arousal levels of facial expressions in high and intermediate intensity categories. Japanese participants, on the other hand, did not discriminate between high and low arousal affect categories to the same extent as did the American and Russian participants. These findings indicate the presence of cultural differences in underlying decoding mechanisms of facial expressions of positive affect intensity. Implications of these results for global advertising are discussed. PMID:22084635

Cultural differences in affect intensity perception in the context of advertising.

PubMed

Pogosyan, Marianna; Engelmann, Jan B

2011-01-01

Cultural differences in the perception of positive affect intensity within an advertising context were investigated among American, Japanese, and Russian participants. Participants were asked to rate the intensity of facial expressions of positive emotions, which displayed either subtle, low intensity, or salient, high intensity expressions of positive affect. In agreement with previous findings from cross-cultural psychological research, current results demonstrate both cross-cultural agreement and differences in the perception of positive affect intensity across the three cultures. Specifically, American participants perceived high arousal (HA) images as significantly less calm than participants from the other two cultures, while the Japanese participants perceived low arousal (LA) images as significantly more excited than participants from the other cultures. The underlying mechanisms of these cultural differences were further investigated through difference scores that probed for cultural differences in perception and categorization of positive emotions. Findings indicate that rating differences are due to (1) perceptual differences in the extent to which HA images were discriminated from LA images, and (2) categorization differences in the extent to which facial expressions were grouped into affect intensity categories. Specifically, American participants revealed significantly higher perceptual differentiation between arousal levels of facial expressions in high and intermediate intensity categories. Japanese participants, on the other hand, did not discriminate between high and low arousal affect categories to the same extent as did the American and Russian participants. These findings indicate the presence of cultural differences in underlying decoding mechanisms of facial expressions of positive affect intensity. Implications of these results for global advertising are discussed.

Low rate of apoptosis and overexpression of bcl-2 in Epstein-Barr virus-associated gastric carcinoma.

PubMed

Kume, T; Oshima, K; Shinohara, T; Takeo, H; Yamashita, Y; Shirakusa, T; Kikuchi, M

1999-06-01

Epstein-Barr virus (EBV) has been demonstrated in about 10% of gastric carcinomas. However, the pathogenetic role of EBV in gastric carcinoma is uncertain. We compared the rate of apoptotic cell death, cell proliferation and the expression of apoptosis-related proteins in gastric carcinomas with or without EBV. Epstein-Barr virus was detected in 40 gastric carcinomas by EBV-encoded small RNA-1 in-situ hybridization. Apoptotic cell death, MIB-1, p53, bcl-2 and bcl-x were examined by the terminal deoxynucleotidyl-mediated dUTP-nick end labelling method and immunohistochemistry. We also included 40 age-, sex- and disease stage-matched EBV-negative cases as a control. The number of apoptotic cells was significantly lower in EBV-positive (20 +/- 15. 1/1000 cells) and bcl-2-positive (17 +/- 12.9/1000 cells) tumours than in EBV-negative (43 +/- 37.1) and bcl-2-negative tumours (38 +/- 32.1, P < 0.001, P < 0.001, respectively). bcl-2 immunostaining was significantly higher in EBV-positive tumours (24 cases) than in EBV-negative tumours (12 cases, P < 0.05). There was no significant difference in bcl-x and p53 expression between EBV-positive and -negative tumours. The number of MIB-1-positive cells in EBV-positive tumours (237 +/- 161/1000) was significantly lower than in EBV-negative tumours (480 +/- 208/1000 cells, P < 0.001). A low rate of apoptosis and high bcl-2 expression were recognized in EBV-positive gastric carcinomas, suggesting that bcl-2 protein is the main inhibitor of apoptosis in EBV-positive carcinomas. In addition, the low apoptotic and proliferative activities may reflect a low biological activity in EBV-positive gastric carcinomas.

[Tripartite-motif protein 25 and pyruvate kinase M2 protein expression in non-small cell lung cancer].

PubMed

Jing, Huai-Zhi; Qiu, Feng; Chen, Shi-Zhi; Su, Lin; Qu, Can

2015-03-01

To investigate the expression of tripartite-motif protein 25 (TRIM25) and pyruvate kinase M2 (PKM2) protein in non-small cell lung cancer (NSCLC) and explore their role in the occurrence and progression of NSCLC. The expressions of TRIM25 and PKM2 protein were detected in 60 NSCLC specimens and 20 adjacent normal lung tissue (>5 cm from the lesions) with immunofluorescence histochemical method and in 10 fresh specimens of NSCLC with Western blotting. The results were analyzed in relation with the clinicopathological features of the patients. The positivity rates of TRIM25 expression was 45% in the 60 lung carcinoma specimens, significantly higher than that in the 20 normal lung tissues (10%, P=0.005). TRIM25 protein was expressed in 28.6% of lung adenocarcinoma tissues and in 59.4% of squamous carcinoma tissues (P=0.017). TRIM25 protein expression was positively correlated with the TNM stages and lymph node metastasis of NSCLC (P<0.05). The expressions of PKM2 protein in 60 cases of lung carcinoma was 73.3%,while in 20 cases of normal lung tissues the expressions was 30%(P=0.001). The positivity rates of PKM2 expression differed significantly between lung adenocarcinoma and squamous carcinoma (57.1% vs 87.5%, P=0.008). An inverse correlation was noted between TRIM25 and PKM2 expressions (P=0.026). TRIM25 and PKM2 protein may participate in the occurrence and progression of NSCLC, and their expressions are inversely correlated.

[Expression of Ki-67 and P53 protein in oral squamous cell carcinoma and its clinical significance].

PubMed

He, Wei; Xiao, Yan; Chen, Wei-min

2015-04-01

To investigate the clinical and pathological features and its relationship with the expression of Ki-67 and p53 protein in oral squamous cell carcinoma. Immunohistochemical SP staining method was used to quantify the protein expression levels of Ki-67 and p53 protein in 10 cases of normal oral mucosa, 16 cases of oral leukoplakia (OLK) tissue, and 48 cases of oral squamous cell carcinoma. The relationship of the expression of Ki-67 and p53 protein to clinical and pathological data was analyzed, and SPSS17.0 software package was used for statistical analysis. The positive expression rate of Ki-67 protein in normal oral mucosa, oral leukoplakia and oral squamous cell carcinoma was 30%, 56.3% and 79.2%, respectively; The positive expression rate of p53 was 0%, 43.8%, and 70.8%, respectively; Ki-67 and p53 expression had significant difference among normal oral mucosa, oral leukoplakia and oral squamous cell carcinoma (P<0.05); The expression of Ki-67 protein was significantly elevated with tumor stage, differentiation and cervical lymph node metastasis (P<0.05); The expression of p53 protein was significantly related to the degree of tumor differentiation (P<0.05); The expression of Ki-67 and p53 was positively correlated in oral squamous cell carcinoma (P<0.05). The high expression of Ki-67 and p53 protein in oral squamous cell carcinoma tissues may play an important role in the development of oral squamous cell carcinoma.

Positive facial expressions during retrieval of self-defining memories.

PubMed

Gandolphe, Marie Charlotte; Nandrino, Jean Louis; Delelis, Gérald; Ducro, Claire; Lavallee, Audrey; Saloppe, Xavier; Moustafa, Ahmed A; El Haj, Mohamad

2017-11-14

In this study, we investigated, for the first time, facial expressions during the retrieval of Self-defining memories (i.e., those vivid and emotionally intense memories of enduring concerns or unresolved conflicts). Participants self-rated the emotional valence of their Self-defining memories and autobiographical retrieval was analyzed with a facial analysis software. This software (Facereader) synthesizes the facial expression information (i.e., cheek, lips, muscles, eyebrow muscles) to describe and categorize facial expressions (i.e., neutral, happy, sad, surprised, angry, scared, and disgusted facial expressions). We found that participants showed more emotional than neutral facial expressions during the retrieval of Self-defining memories. We also found that participants showed more positive than negative facial expressions during the retrieval of Self-defining memories. Interestingly, participants attributed positive valence to the retrieved memories. These findings are the first to demonstrate the consistency between facial expressions and the emotional subjective experience of Self-defining memories. These findings provide valuable physiological information about the emotional experience of the past.

Expression of glypican-3 is highly associated with pediatric hepatoblastoma: a systemic analysis.

PubMed

Xiong, Xiao-Li; Qin, Huan; Yan, Su-Qi; Zhou, Li-Shan; Chen, Peng; Zhao, Dong- Chi

2015-01-01

Glypican-3 (GPC3) is reported to be an oncofetal protein that is a useful diagnostic immunomarker for hepatoblastoma. However, the results are not inclusive. This study systemically investigated the association between expression of GPC3 and pediatric hepatoblastoma. Clinical studies evaluating the association were identified using a predefined search strategy. GPC3 immunohistochemistry was applied in the pathological diagnosis of hepatoblastoma using the monoclonal antibodies with formalin-fixed and paraffin-embedded specimens. Positive predictive rates for the association between expression of GPC3 and pediatric hepatoblastoma were calculated. Specimens from four clinical studies which including 134 patients with pediatric hepatoblastoma tested by GPC3 immunohistochemistry were considered eligible for inclusion. Systemic analysis showed that, in all patients, pooled positive predictive rate of the association between expression of GPC3 and pediatric hepatoblastoma was 95.5% (128/134). This systemic analysis suggests that the expression of glypican-3 is highly associated with the diagnosis of pediatric hepatoblastoma.

Clinical efficacy of gamma knife and surgery treatment of mesial temporal lobe epilepsy and their effects on EF-Tumt and EF-Tsmt expression.

PubMed

Wang, X-Q; Zhang, X-D; Han, Y-M; Shi, X-F; Lan, Z-B; Men, X-X; Pan, Y-W

2017-04-01

To study the clinical efficacy of gamma knife and surgery treatment of mesial temporal lobe epilepsy (MTLE) and their effects on EF-Tumt and EF-Tsmt expression. The data of 78 cases of MTLE patients treated in our hospital from April 2011 to March 2013 were retrospectively analyzed. The patients were divided into two groups according to the treatment methods: the surgery group (including 41 cases) and the gamma knife group (including 37 cases). The clinical efficacy, the occurrence and recurrence of complications were evaluated, respectively; meanwhile, the expression of the EF-Tumt protein and EF-Tsmt protein in brain tissue were analyzed. The difference between the efficacy rate of the two groups showed no statistical significance (χ2=0.960, p>0.05). The complication rate of the gamma knife group was significantly lower than that of the control group (χ2=6.430, p<0.05). The recurrence rate of the patients in the gamma knife group was significantly lower than that of the patients in the surgery group (p>0.05). Within the two groups, the positive expression granum of EF-Tsmt protein and EF-Tumt protein of the two groups after treatment were significantly lower than that before treatment (p<0.05). After treatment, the positive expression granum of EF-Tsmt protein of the patients in the gamma knife group was obviously more than that of the patients in the surgery group (p<0.05). The difference between the positive expression granum of EF-Tumt protein of the two groups showed no statistical significance (p>0.05). Before and after treatment within the group, the positive cell of EF-Tsmt protein and EF-Tumt protein of the two groups of patients after treatment were significantly lower than that before treatment (p<0.05). After treatment, the difference between the EF-Tsmt protein positive cell and the EF-Tumt protein positive cell of the two groups of patients showed no statistical significance (p>0.05). Both surgery and gamma knife could treat MTLE effectively, and the efficacy may be related to the ability to reduce the expression of EF-Tsmt protein and EF-Tumt protein in brain tissue.

[Antitumor effect of baicalin on rat brain glioma].

PubMed

Hu, Yong-zhen; Wang, Dian-hong; Luan, Yu; Gong, Hai-dong

2013-01-01

To investigate the therapeutic mechanism of baicalin on rat brain glioma. Deep brain glioma models were established by injection of glioma cell line C6 cells into the brain of Wistar rats. The rats at 7 days after modeling were randomly divided into tumor control group (0.9% NaCl solution 30 mg×kg(-1)×d(-1) gavage)and experimental groups. The experimental rats was divided into 3 groups: low dose group (50 mg×kg(-1)×d(-1)), middle dose group (100 mg×kg(-1)×d(-1)) and high dose group (200 mg×kg(-1)×d(-1)), given the baicalin by gavage. Pathological and electron microscopic changes were observed. The expressions of p53 and Bcl-2 were determined by immunohistochemistry, and the changes of MRI, the average survival time and body weight of the rats in each group after treatments were analyzed. Compared with the control group, the tumor diameter and volume of high dose group rats before sacrifice were significantly reduced (P < 0.01), and the survival time was significantly prolonged (P < 0.01). Immunohistochemistry revealed strong positive expression rate of mutant p53 (84.47 ± 3.74)% and moderately positive rate (47.28 ± 2.38)% in the control group, significantly higher than that in the negative group (12.91 ± 1.07)% (P < 0.01). The positive rate of mutant p53 of the high dose group was (46.42 ± 2.19)%, significantly lower than that of the control group (84.47 ± 3.74)% (P < 0.01). The expression rate of Bcl-2 in the control group was strongly positive (86.51 ± 4.17)% and moderate positive (48.19 ± 2.11)%, significantly higher than that of the negative group (10.36 ± 1.43)% (P < 0.01). Electron microscopy revealed that baicalin caused damages of the cell nuclei and organelles in the gliomas. Baicalin has significant inhibitory effect on glioma in vivo, and its mechanism may be related to cell apoptosis induced by down-regulated expression of mutant p53, but not related with Bcl-2 expression.

Protein disorder is positively correlated with gene expression in E. coli

PubMed Central

Paliy, Oleg; Gargac, Shawn M.; Cheng, Yugong; Uversky, Vladimir N.; Dunker, A. Keith

2009-01-01

We considered on a global scale the relationship between the predicted fraction of protein disorder and RNA and protein expression in E. coli. Fraction of protein disorder correlated positively with both measured RNA expression levels of E. coli genes in three different growth media and with predicted abundance levels of E. coli proteins. Though weak, the correlation was highly significant. Correlation of protein disorder with RNA expression did not depend on the growth rate of E. coli cultures and was not caused by a small subset of genes showing exceptionally high concordance in their disorder and expression levels. Global analysis was complemented by detailed consideration of several groups of proteins. PMID:18465893

Judgments of subtle facial expressions of emotion.

PubMed

Matsumoto, David; Hwang, Hyisung C

2014-04-01

Most studies on judgments of facial expressions of emotion have primarily utilized prototypical, high-intensity expressions. This paper examines judgments of subtle facial expressions of emotion, including not only low-intensity versions of full-face prototypes but also variants of those prototypes. A dynamic paradigm was used in which observers were shown a neutral expression followed by the target expression to judge, and then the neutral expression again, allowing for a simulation of the emergence of the expression from and then return to a baseline. We also examined how signal and intensity clarities of the expressions (explained more fully in the Introduction) were associated with judgment agreement levels. Low-intensity, full-face prototypical expressions of emotion were judged as the intended emotion at rates significantly greater than chance. A number of the proposed variants were also judged as the intended emotions. Both signal and intensity clarities were individually associated with agreement rates; when their interrelationships were taken into account, signal clarity independently predicted agreement rates but intensity clarity did not. The presence or absence of specific muscles appeared to be more important to agreement rates than their intensity levels, with the exception of the intensity of zygomatic major, which was positively correlated with agreement rates for judgments of joy.

Low Ki67/high ATM protein expression in malignant tumors predicts favorable prognosis in a retrospective study of early stage hormone receptor positive breast cancer.

PubMed

Feng, Xiaolan; Li, Haocheng; Kornaga, Elizabeth N; Dean, Michelle; Lees-Miller, Susan P; Riabowol, Karl; Magliocco, Anthony M; Morris, Don; Watson, Peter H; Enwere, Emeka K; Bebb, Gwyn; Paterson, Alexander

2016-12-27

This study was designed to investigate the combined influence of ATM and Ki67 on clinical outcome in early stage hormone receptor positive breast cancer (ES-HPBC), particularly in patients with smaller tumors (< 4 cm) and fewer than four positive lymph nodes. 532 formalin-fixed paraffin-embedded specimens of resected primary breast tumors were used to construct a tissue microarray. Samples from 297 patients were suitable for final statistical analysis. We detected ATM and Ki67 proteins using fluorescence and brightfield immunohistochemistry respectively, and quantified their expression with digital image analysis. Data on expression levels were subsequently correlated with clinical outcome. Remarkably, ATM expression was useful to stratify the low Ki67 group into subgroups with better or poorer prognosis. Specifically, in the low Ki67 subgroup defined as having smaller tumors and no positive nodes, patients with high ATM expression showed better outcome than those with low ATM, with estimated survival rates of 96% and 89% respectively at 15 years follow up (p = 0.04). Similarly, low-Ki67 patients with smaller tumors, 1-3 positive nodes and high ATM also had significantly better outcomes than their low ATM counterparts, with estimated survival rates of 88% and 46% respectively (p = 0.03) at 15 years follow up. Multivariable analysis indicated that the combination of high ATM and low Ki67 is prognostic of improved survival, independent of tumor size, grade, and lymph node status (p = 0.02). These data suggest that the prognostic value of Ki67 can be improved by analyzing ATM expression in ES-HPBC.

Low Ki67/high ATM protein expression in malignant tumors predicts favorable prognosis in a retrospective study of early stage hormone receptor positive breast cancer

PubMed Central

Feng, Xiaolan; Li, Haocheng; Kornaga, Elizabeth N.; Dean, Michelle; Lees-Miller, Susan P.; Riabowol, Karl; Magliocco, Anthony M.; Morris, Don; Watson, Peter H.; Enwere, Emeka K.; Bebb, Gwyn; Paterson, Alexander

2016-01-01

Introduction This study was designed to investigate the combined influence of ATM and Ki67 on clinical outcome in early stage hormone receptor positive breast cancer (ES-HPBC), particularly in patients with smaller tumors (< 4 cm) and fewer than four positive lymph nodes. Methods 532 formalin-fixed paraffin-embedded specimens of resected primary breast tumors were used to construct a tissue microarray. Samples from 297 patients were suitable for final statistical analysis. We detected ATM and Ki67 proteins using fluorescence and brightfield immunohistochemistry respectively, and quantified their expression with digital image analysis. Data on expression levels were subsequently correlated with clinical outcome. Results Remarkably, ATM expression was useful to stratify the low Ki67 group into subgroups with better or poorer prognosis. Specifically, in the low Ki67 subgroup defined as having smaller tumors and no positive nodes, patients with high ATM expression showed better outcome than those with low ATM, with estimated survival rates of 96% and 89% respectively at 15 years follow up (p = 0.04). Similarly, low-Ki67 patients with smaller tumors, 1-3 positive nodes and high ATM also had significantly better outcomes than their low ATM counterparts, with estimated survival rates of 88% and 46% respectively (p = 0.03) at 15 years follow up. Multivariable analysis indicated that the combination of high ATM and low Ki67 is prognostic of improved survival, independent of tumor size, grade, and lymph node status (p = 0.02). Conclusions These data suggest that the prognostic value of Ki67 can be improved by analyzing ATM expression in ES-HPBC. PMID:27741524

Perspective taking combats automatic expressions of racial bias.

PubMed

Todd, Andrew R; Bodenhausen, Galen V; Richeson, Jennifer A; Galinsky, Adam D

2011-06-01

Five experiments investigated the hypothesis that perspective taking--actively contemplating others' psychological experiences--attenuates automatic expressions of racial bias. Across the first 3 experiments, participants who adopted the perspective of a Black target in an initial context subsequently exhibited more positive automatic interracial evaluations, with changes in automatic evaluations mediating the effect of perspective taking on more deliberate interracial evaluations. Furthermore, unlike other bias-reduction strategies, the interracial positivity resulting from perspective taking was accompanied by increased salience of racial inequalities (Experiment 3). Perspective taking also produced stronger approach-oriented action tendencies toward Blacks (but not Whites; Experiment 4). A final experiment revealed that face-to-face interactions with perspective takers were rated more positively by Black interaction partners than were interactions with nonperspective takers--a relationship that was mediated by perspective takers' increased approach-oriented nonverbal behaviors (as rated by objective, third-party observers). These findings indicate that perspective taking can combat automatic expressions of racial biases without simultaneously decreasing sensitivity to ongoing racial disparities. 2011 APA, all rights reserved

Happy but not so approachable: the social judgments of individuals with generalized social phobia.

PubMed

Campbell, D W; Sareen, J; Stein, M B; Kravetsky, L B; Paulus, M P; Hassard, S T; Reiss, J P

2009-01-01

We examined social approachability judgments in a psychiatric population that frequently experiences interpersonal difficulties and reduced social satisfaction, individuals with generalized social phobia (gSP). Our objective was to broaden the understanding of the social cognitive tendencies of individuals with gSP by systematically investigating their interpretation of positive facial expressions. We hypothesized that approachability ratings would be lower for positive as well as negative emotional faces in the gSP group compared to the healthy comparison group. Each participant evaluated 24 emotional faces presented on a computer screen. Participants first labeled the faces as either happy, disgust, or angry in emotional expression, and then they rated each face's approachability. Analysis of variance and post hoc analyses were used to identify group, emotion, and group by emotion rating differences. Happy face approachability ratings were higher than disgust and anger in both groups. The central finding was that individuals with gSP rated happy faces as less approachable than the healthy participants and that degree of social anxiety was associated with lower approachability ratings within the gSP sample. Explicit approachability judgments of negative faces did not differ as predicted. Consistent with earlier indirect evidence of interpretation biases of positive social emotional information, this study reveals that individuals with gSP demonstrate explicit, subjective social interpretation biases of overtly positive social feedback. The therapeutic relevance of these results is discussed.

Neural evidence for cultural differences in the valuation of positive facial expressions.

PubMed

Park, BoKyung; Tsai, Jeanne L; Chim, Louise; Blevins, Elizabeth; Knutson, Brian

2016-02-01

European Americans value excitement more and calm less than Chinese. Within cultures, European Americans value excited and calm states similarly, whereas Chinese value calm more than excited states. To examine how these cultural differences influence people's immediate responses to excited vs calm facial expressions, we combined a facial rating task with functional magnetic resonance imaging. During scanning, European American (n = 19) and Chinese (n = 19) females viewed and rated faces that varied by expression (excited, calm), ethnicity (White, Asian) and gender (male, female). As predicted, European Americans showed greater activity in circuits associated with affect and reward (bilateral ventral striatum, left caudate) while viewing excited vs calm expressions than did Chinese. Within cultures, European Americans responded to excited vs calm expressions similarly, whereas Chinese showed greater activity in these circuits in response to calm vs excited expressions regardless of targets' ethnicity or gender. Across cultural groups, greater ventral striatal activity while viewing excited vs. calm expressions predicted greater preference for excited vs calm expressions months later. These findings provide neural evidence that people find viewing the specific positive facial expressions valued by their cultures to be rewarding and relevant. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Programmed death-1 ligands 1 and 2 expression in cutaneous squamous cell carcinoma and their relationship with tumour- infiltrating dendritic cells.

PubMed

Jiao, Q; Liu, C; Li, W; Li, W; Fang, F; Qian, Q; Zhang, X

2017-06-01

The programmed death-1 (PD-1) receptor ligands, PD-L1 and PD-L2, are co-stimulatory molecules that contribute to the negative regulation of T lymphocyte activation. It is still unclear whether there is correlation between PD-L1 or PD-L2 and tumour-infiltrating dendritic cells (TIDCs) in cutaneous squamous cell carcinoma (CSCC). The aim of this study was to analyse PD-L1 and PD-L2 expression and dendritic cells infiltration in tumour tissue of CSCC patients and investigate their clinical significance. Immunohistochemical analysis was used to evaluate the expression of PD-L1, PD-L2, CD1a and CD83 in 61 CSCC tissues. The immunofluoresence double-labelling technique was performed to detect the co-expression of PD-L1 or PD-L2 and CD1a or CD83 in tumour tissues. We found that 25 of 61 cases CSCC (40·98%) exhibited positivity for PD-L1, whereas 37 of 61 cases CSCC (60·66%) exhibited positivity for PD-L2. A higher percentage of CD1a-positive cases were observed on both PD-L1-positive and PD-L2-positive specimens compared with that of CD83-positive cases (92·29% versus 37·60%, 83·20% versus 33·16%). The expression of PD-L1 and PD-L2 on CD1a + cells was significantly higher than that on CD83 + cells in tumour tissues of CSCC patients. Furthermore, the expression rate of PD-L1 was associated with UICC stage, and the expression rate of PD-L2 was associated with predominant differentiation and tumour size in CSCC. Our results indicated that higher expression of PD-L1 and PD-L2 on CD1a + cells than that on CD83 + cells in CSCC tumour tissues may contribute to negative regulation in anti-tumour immune responses. © 2017 British Society for Immunology.

The relationship between prelinguistic vocalization and later expressive vocabulary in young children with developmental delay.

PubMed

McCathren, R B; Yoder, P J; Warren, S F

1999-08-01

This study tested the relationship between prelinguistic vocalization and expressive vocabulary 1 year later in young children with mild to moderate developmental delays. Three vocalization variables were tested: rate of all vocalization, rate of vocalizations with consonants, and rate of vocalizations used interactively. The 58 toddlers in the study were 17-34 months old, not sensory impaired, and had Bayley Mental Development Indices (Bayley, 1969; Bayley, 1993) from 35-85. In addition, the children had fewer than 3 words in their expressive vocabularies and during classroom observation each showed at least one instance of intentional prelinguistic communication before testing. Selected sections of the Communication and Symbolic Behavior Scales procedures (CSBS; Wetherby & Prizant, 1993) were administered at the beginning and at the end of the study. The vocal measures were obtained in the initial CSBS session. One measure of expressive vocabulary was obtained in the CSBS session at the end of the study. In addition, expressive vocabulary was measured in a nonstructured play session at the end of the study. We predicted that rate of vocalization, rate of vocalizations with consonants, and rate of vocalizations used interactively would all be positively related to later expressive vocabulary. The results confirmed the predictions.

Selection-driven evolution of sex-biased genes is consistent with sexual selection in Arabidopsis thaliana.

PubMed

Gossmann, Toni I; Schmid, Marc W; Grossniklaus, Ueli; Schmid, Karl J

2014-03-01

Sex-biased genes are genes with a preferential or specific expression in one sex and tend to show an accelerated rate of evolution in animals. Various hypotheses--which are not mutually exclusive--have been put forth to explain observed patterns of rapid evolution. One possible explanation is positive selection, but this has been shown only in few animal species and mostly for male-specific genes. Here, we present a large-scale study that investigates evolutionary patterns of sex-biased genes in the predominantly self-fertilizing plant Arabidopsis thaliana. Unlike most animal species, A. thaliana does not possess sex chromosomes, its flowers develop both male and female sexual organs, and it is characterized by low outcrossing rates. Using cell-specific gene expression data, we identified genes whose expression is enriched in comparison with all other tissues in the male and female gametes (sperm, egg, and central cell), as well as in synergids, pollen, and pollen tubes, which also play an important role in reproduction. Genes specifically expressed in gametes and synergids show higher rates of protein evolution compared with the genome-wide average and no evidence for positive selection. In contrast, pollen- and pollen tube-specific genes not only have lower rates of protein evolution but also exhibit a higher proportion of adaptive amino acid substitutions. We show that this is the result of increased levels of purifying and positive selection among genes with pollen- and pollen tube-specific expression. The increased proportion of adaptive substitutions cannot be explained by the fact that pollen- and pollen tube-expressed genes are enriched in segmental duplications, are on average older, or have a larger effective population size. Our observations are consistent with prezygotic sexual selection as a result of interactions during pollination and pollen tube growth such as pollen tube competition.

Computational exploration of cis-regulatory modules in rhythmic expression data using the "Exploration of Distinctive CREs and CRMs" (EDCC) and "CRM Network Generator" (CNG) programs.

PubMed

Bekiaris, Pavlos Stephanos; Tekath, Tobias; Staiger, Dorothee; Danisman, Selahattin

2018-01-01

Understanding the effect of cis-regulatory elements (CRE) and clusters of CREs, which are called cis-regulatory modules (CRM), in eukaryotic gene expression is a challenge of computational biology. We developed two programs that allow simple, fast and reliable analysis of candidate CREs and CRMs that may affect specific gene expression and that determine positional features between individual CREs within a CRM. The first program, "Exploration of Distinctive CREs and CRMs" (EDCC), correlates candidate CREs and CRMs with specific gene expression patterns. For pairs of CREs, EDCC also determines positional preferences of the single CREs in relation to each other and to the transcriptional start site. The second program, "CRM Network Generator" (CNG), prioritizes these positional preferences using a neural network and thus allows unbiased rating of the positional preferences that were determined by EDCC. We tested these programs with data from a microarray study of circadian gene expression in Arabidopsis thaliana. Analyzing more than 1.5 million pairwise CRE combinations, we found 22 candidate combinations, of which several contained known clock promoter elements together with elements that had not been identified as relevant to circadian gene expression before. CNG analysis further identified positional preferences of these CRE pairs, hinting at positional information that may be relevant for circadian gene expression. Future wet lab experiments will have to determine which of these combinations confer daytime specific circadian gene expression.

Computational exploration of cis-regulatory modules in rhythmic expression data using the “Exploration of Distinctive CREs and CRMs” (EDCC) and “CRM Network Generator” (CNG) programs

PubMed Central

Staiger, Dorothee

2018-01-01

Understanding the effect of cis-regulatory elements (CRE) and clusters of CREs, which are called cis-regulatory modules (CRM), in eukaryotic gene expression is a challenge of computational biology. We developed two programs that allow simple, fast and reliable analysis of candidate CREs and CRMs that may affect specific gene expression and that determine positional features between individual CREs within a CRM. The first program, “Exploration of Distinctive CREs and CRMs” (EDCC), correlates candidate CREs and CRMs with specific gene expression patterns. For pairs of CREs, EDCC also determines positional preferences of the single CREs in relation to each other and to the transcriptional start site. The second program, “CRM Network Generator” (CNG), prioritizes these positional preferences using a neural network and thus allows unbiased rating of the positional preferences that were determined by EDCC. We tested these programs with data from a microarray study of circadian gene expression in Arabidopsis thaliana. Analyzing more than 1.5 million pairwise CRE combinations, we found 22 candidate combinations, of which several contained known clock promoter elements together with elements that had not been identified as relevant to circadian gene expression before. CNG analysis further identified positional preferences of these CRE pairs, hinting at positional information that may be relevant for circadian gene expression. Future wet lab experiments will have to determine which of these combinations confer daytime specific circadian gene expression. PMID:29298348

What Facial Appearance Reveals Over Time: When Perceived Expressions in Neutral Faces Reveal Stable Emotion Dispositions

PubMed Central

Adams, Reginald B.; Garrido, Carlos O.; Albohn, Daniel N.; Hess, Ursula; Kleck, Robert E.

2016-01-01

It might seem a reasonable assumption that when we are not actively using our faces to express ourselves (i.e., when we display nonexpressive, or neutral faces), those around us will not be able to read our emotions. Herein, using a variety of expression-related ratings, we examined whether age-related changes in the face can accurately reveal one’s innermost affective dispositions. In each study, we found that expressive ratings of neutral facial displays predicted self-reported positive/negative dispositional affect, but only for elderly women, and only for positive affect. These findings meaningfully replicate and extend earlier work examining age-related emotion cues in the face of elderly women (Malatesta et al., 1987a). We discuss these findings in light of evidence that women are expected to, and do, smile more than men, and that the quality of their smiles predicts their life satisfaction. Although ratings of old male faces did not significantly predict self-reported affective dispositions, the trend was similar to that found for old female faces. A plausible explanation for this gender difference is that in the process of attenuating emotional expressions over their lifetimes, old men reveal less evidence of their total emotional experiences in their faces than do old women. PMID:27445944

The significance of granzyme B expression in patients with angiocentric lymphoma of the head and neck.

PubMed

Kim, G E; Yang, W I; Lee , S; Kim, Y B; Suh, C O; Yoon, J H; Oh, Y T; Chung, H C; Kim, B S

2001-06-15

The objectives of this study were to establish a correlation between granzyme B expression and the clinicopathologic characteristics of patients with angiocentric lymphomas of the head and neck and to determine whether the expression of granzyme B had any influence on the treatment outcomes of such patients. Fifty-seven patients with angiocentric lymphoma of the head and neck who were treated between 1987 and 1996 were divided into two groups according to whether their tumors were immunoreactive for granzyme B: the granzyme B negative group (n = 22 patients) and the granzyme B positive group (n = 35 patients). The clinicopathologic features, immunohistochemical findings, patterns of disease failure, and survival data for the granzyme B positive group were compared with those for the granzyme B negative group. Greater than 60% of patients with angiocentric lymphoma of the head and neck were shown to have granzyme B positive tumors. All tumors that expressed granzyme B also consistently coexpressed CD56, indicating that they probably are the neoplastic equivalent of either natural killer (NK) cells or activated cytotoxic T cells. Although there were no significant differences in histopathologic features or expression of CD45RO and polyclonal CD3-epsilon between the groups, the Epstein-Barr virus genomes were detected more frequently in the granzyme B positive group compared with the granzyme B negative group. Despite a similar rate of complete remission after initial treatment, the locoregional recurrence rate of patients in the granzyme B positive group was much higher compared with patients in the granzyme B negative group. In addition, compared with patients in the granzyme B negative group, patients in the granzyme B positive group also had an increased risk of systemic disease recurrence and a decreased overall survival rate. The data indicate that the cytotoxic granule-associated protein, granzyme B, may be used as an additional marker for identifying NK/T-cell lymphoma and as a prognostic indicator for risk assessment in patients with angiocentric lymphoma of the head and neck. Copyright 2001 American Cancer Society.

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) expression in colorectal cancer.

PubMed

Nagano, Hideki; Goi, Takanori; Koneri, Kenji; Hirono, Yasuo; Katayama, Kanji; Yamaguchi, Akio

2007-12-01

Vascular endothelial growth factor (VEGF) is known as an important factor in the growth and metastasis of cancer cells. In 2001, a novel angiogenesis factor, endocrine gland-derived vascular endothelial growth factor (EG-VEGF), was cloned. In this study, we investigated the expression of EG-VEGF in colorectal cancer, the relationship between its expression and clinicopathological factors, and the in vitro activity of EG-VEGF transfectants. We determined expression levels of EG-VEGF in 113 advanced colorectal cancers resected in our hospital by quantitative PCR, and compared the expression levels and clinicopathological findings by multivariate analyses. The expression of EG-VEGF mRNA was positive in 31 cancers and negative in 82 cancers. We found that compared with the negative expression of the EG-VEGF gene, its positive expression was more frequently associated with hematogenous metastasis, and was associated with a poorer survival rate. In addition, EG-VEGF transfectants showed a higher degree of in vitro tubular formation than control cells. We speculate that, in colorectal cancers, the EG-VEGF gene functions as an important factor in angiogenesis in primary and metastatic lesions, and consider that it is useful as a novel prognostic factor. EG-VEGF molecule-targeted therapy has the potential for improving survival rates.

[The Expression of Pokemon in Endometrial Carcinoma Tissue and the Correlation with Mutant p53].

PubMed

Yi, Tian-jin; Wang, Ping

2016-05-01

To detect the expression of Pokemon in endometrial carcinoma (EC), to provide preliminary theoretical basis for clarifying pathogenesis and searching for effective targets. Ninety-eight cases of endometrial tissue paraffin specimens form July 2012 to July 2014 in West China Second University Hospital, Sichuan University, were collected, including: EC group, consisting of adenocarcinoma 23 cases, adenosquamous 12 cases, serous 3 cases, mucinous 11 cases and clear cell 9 cases, and control group, consisting of atypical hyperplasia endometrium 20 cases and normal endometrium 20 cases (secretory 10 cases, hyperplasia 10 cases). Immunohistochemistry was used to detect the expression of Pokemonin each section, analyzing the correlation of Pokemon expression with clinicopathologic characteristics and p53 expression. The positive rate of Pokemon in normal endometrium was 25% (5/20), significantly lower than that in atypical hyperplasia endometrium (60.0%, 12/20) and EC (93.1%, 54/58) (P < 0.05); the rate in type II was 97. 12% (34/35), significantly higher than that in type I (86.96%, 20/23) (P = 0.018). The positive rate of Pokemon in III-IV stage, type II and Ki-67 ≥ 50 EC tissue was much higher (P = 0.012, 0.023, 0.029). In type II EC tissue, the correlation index between Pokemon and p53 is 0.669 (P = 0.000). The over expression of Pokemon upregulates the expression of mutant p53, which may be one of the carcinogenesis modes in type II EC.

Cross-Cultural Differences in the Processing of Non-Verbal Affective Vocalizations by Japanese and Canadian Listeners

PubMed Central

Koeda, Michihiko; Belin, Pascal; Hama, Tomoko; Masuda, Tadashi; Matsuura, Masato; Okubo, Yoshiro

2013-01-01

The Montreal Affective Voices (MAVs) consist of a database of non-verbal affect bursts portrayed by Canadian actors, and high recognitions accuracies were observed in Canadian listeners. Whether listeners from other cultures would be as accurate is unclear. We tested for cross-cultural differences in perception of the MAVs: Japanese listeners were asked to rate the MAVs on several affective dimensions and ratings were compared to those obtained by Canadian listeners. Significant Group × Emotion interactions were observed for ratings of Intensity, Valence, and Arousal. Whereas Intensity and Valence ratings did not differ across cultural groups for sad and happy vocalizations, they were significantly less intense and less negative in Japanese listeners for angry, disgusted, and fearful vocalizations. Similarly, pleased vocalizations were rated as less intense and less positive by Japanese listeners. These results demonstrate important cross-cultural differences in affective perception not just of non-verbal vocalizations expressing positive affect (Sauter et al., 2010), but also of vocalizations expressing basic negative emotions. PMID:23516137

Cross-cultural differences in the processing of non-verbal affective vocalizations by Japanese and canadian listeners.

PubMed

Koeda, Michihiko; Belin, Pascal; Hama, Tomoko; Masuda, Tadashi; Matsuura, Masato; Okubo, Yoshiro

2013-01-01

The Montreal Affective Voices (MAVs) consist of a database of non-verbal affect bursts portrayed by Canadian actors, and high recognitions accuracies were observed in Canadian listeners. Whether listeners from other cultures would be as accurate is unclear. We tested for cross-cultural differences in perception of the MAVs: Japanese listeners were asked to rate the MAVs on several affective dimensions and ratings were compared to those obtained by Canadian listeners. Significant Group × Emotion interactions were observed for ratings of Intensity, Valence, and Arousal. Whereas Intensity and Valence ratings did not differ across cultural groups for sad and happy vocalizations, they were significantly less intense and less negative in Japanese listeners for angry, disgusted, and fearful vocalizations. Similarly, pleased vocalizations were rated as less intense and less positive by Japanese listeners. These results demonstrate important cross-cultural differences in affective perception not just of non-verbal vocalizations expressing positive affect (Sauter et al., 2010), but also of vocalizations expressing basic negative emotions.

Human Empathy, Personality and Experience Affect the Emotion Ratings of Dog and Human Facial Expressions.

PubMed

Kujala, Miiamaaria V; Somppi, Sanni; Jokela, Markus; Vainio, Outi; Parkkonen, Lauri

2017-01-01

Facial expressions are important for humans in communicating emotions to the conspecifics and enhancing interpersonal understanding. Many muscles producing facial expressions in humans are also found in domestic dogs, but little is known about how humans perceive dog facial expressions, and which psychological factors influence people's perceptions. Here, we asked 34 observers to rate the valence, arousal, and the six basic emotions (happiness, sadness, surprise, disgust, fear, and anger/aggressiveness) from images of human and dog faces with Pleasant, Neutral and Threatening expressions. We investigated how the subjects' personality (the Big Five Inventory), empathy (Interpersonal Reactivity Index) and experience of dog behavior affect the ratings of dog and human faces. Ratings of both species followed similar general patterns: human subjects classified dog facial expressions from pleasant to threatening very similarly to human facial expressions. Subjects with higher emotional empathy evaluated Threatening faces of both species as more negative in valence and higher in anger/aggressiveness. More empathetic subjects also rated the happiness of Pleasant humans but not dogs higher, and they were quicker in their valence judgments of Pleasant human, Threatening human and Threatening dog faces. Experience with dogs correlated positively with ratings of Pleasant and Neutral dog faces. Personality also had a minor effect on the ratings of Pleasant and Neutral faces in both species. The results imply that humans perceive human and dog facial expression in a similar manner, and the perception of both species is influenced by psychological factors of the evaluators. Especially empathy affects both the speed and intensity of rating dogs' emotional facial expressions.

Human Empathy, Personality and Experience Affect the Emotion Ratings of Dog and Human Facial Expressions

PubMed Central

Kujala, Miiamaaria V.; Somppi, Sanni; Jokela, Markus; Vainio, Outi; Parkkonen, Lauri

2017-01-01

Facial expressions are important for humans in communicating emotions to the conspecifics and enhancing interpersonal understanding. Many muscles producing facial expressions in humans are also found in domestic dogs, but little is known about how humans perceive dog facial expressions, and which psychological factors influence people’s perceptions. Here, we asked 34 observers to rate the valence, arousal, and the six basic emotions (happiness, sadness, surprise, disgust, fear, and anger/aggressiveness) from images of human and dog faces with Pleasant, Neutral and Threatening expressions. We investigated how the subjects’ personality (the Big Five Inventory), empathy (Interpersonal Reactivity Index) and experience of dog behavior affect the ratings of dog and human faces. Ratings of both species followed similar general patterns: human subjects classified dog facial expressions from pleasant to threatening very similarly to human facial expressions. Subjects with higher emotional empathy evaluated Threatening faces of both species as more negative in valence and higher in anger/aggressiveness. More empathetic subjects also rated the happiness of Pleasant humans but not dogs higher, and they were quicker in their valence judgments of Pleasant human, Threatening human and Threatening dog faces. Experience with dogs correlated positively with ratings of Pleasant and Neutral dog faces. Personality also had a minor effect on the ratings of Pleasant and Neutral faces in both species. The results imply that humans perceive human and dog facial expression in a similar manner, and the perception of both species is influenced by psychological factors of the evaluators. Especially empathy affects both the speed and intensity of rating dogs’ emotional facial expressions. PMID:28114335

C5a receptor expression is associated with poor prognosis in urothelial cell carcinoma patients treated with radical cystectomy or nephroureterectomy.

PubMed

Wada, Yoshihiro; Maeda, Yoshihiro; Kubo, Tatsuko; Kikuchi, Ken; Eto, Masatoshi; Imamura, Takahisa

2016-11-01

Patients with aggressive urothelial cell carcinoma (UCC) that undergo radical cystectomy or nephroureterectomy exhibit markedly high rates of disease recurrence and mortality. To select appropriate adjuvant thxerapies in addition to radical surgery, the identification of predictive prognostic markers for UCC patients is required. The aim of the present study was to identify such markers, by evaluating the association of UCC complement component 5 (C5) fragment a (C5a)receptor (C5aR) expression, detected using immunohistochemistry, with clinicopathological parameters and survival outcomes of UCC patients. The results revealed that C5aR was expressed in cancer cells, particularly at the invasive front, but not in noncancerous urothelial cells or adjacent cells. The UCC C5aR-positive rate of patients treated with radical surgeries was 73% (38/52) and the rate was 83% (20/24) at stages I-II of disease. No correlation between C5aR expression and any of clinicopathological parameters, which included gender, tumor location, World Health Organization grade, T stage, vessel invasion and stage of disease, was identified. However, univariate and multivariate analyses revealed that C5aR-positive UCC patients exhibited significantly lower overall survival rates [hazard ratio (HR), 3.14; 95% confidence interval (CI), 1.03-9.60; P=0.035 and HR, 3.92; 95% CI, 1.15-13.4; P=0.029, respectively] and 5-year survival rates (0.42 vs. 0.83) compared with C5aR-negative UCC patients. Furthermore, 5-year survival and disease-specific survival rates were lower in patients with C5aR-positive UCC (0.51; 95% CI, 0.30-0.71) than patients with C5aR-negative UCC (0.83; 95% CI, 0.62-1.00). These results indicate that UCC C5aR expression is predictive of poor patient outcomes and thus may lead to the appropriate selection of adjuvant therapies at earlier UCC stages, which could improve patient prognosis.

C5a receptor expression is associated with poor prognosis in urothelial cell carcinoma patients treated with radical cystectomy or nephroureterectomy

PubMed Central

Wada, Yoshihiro; Maeda, Yoshihiro; Kubo, Tatsuko; Kikuchi, Ken; Eto, Masatoshi; Imamura, Takahisa

2016-01-01

Patients with aggressive urothelial cell carcinoma (UCC) that undergo radical cystectomy or nephroureterectomy exhibit markedly high rates of disease recurrence and mortality. To select appropriate adjuvant thxerapies in addition to radical surgery, the identification of predictive prognostic markers for UCC patients is required. The aim of the present study was to identify such markers, by evaluating the association of UCC complement component 5 (C5) fragment a (C5a)receptor (C5aR) expression, detected using immunohistochemistry, with clinicopathological parameters and survival outcomes of UCC patients. The results revealed that C5aR was expressed in cancer cells, particularly at the invasive front, but not in noncancerous urothelial cells or adjacent cells. The UCC C5aR-positive rate of patients treated with radical surgeries was 73% (38/52) and the rate was 83% (20/24) at stages I–II of disease. No correlation between C5aR expression and any of clinicopathological parameters, which included gender, tumor location, World Health Organization grade, T stage, vessel invasion and stage of disease, was identified. However, univariate and multivariate analyses revealed that C5aR-positive UCC patients exhibited significantly lower overall survival rates [hazard ratio (HR), 3.14; 95% confidence interval (CI), 1.03–9.60; P=0.035 and HR, 3.92; 95% CI, 1.15–13.4; P=0.029, respectively] and 5-year survival rates (0.42 vs. 0.83) compared with C5aR-negative UCC patients. Furthermore, 5-year survival and disease-specific survival rates were lower in patients with C5aR-positive UCC (0.51; 95% CI, 0.30–0.71) than patients with C5aR-negative UCC (0.83; 95% CI, 0.62–1.00). These results indicate that UCC C5aR expression is predictive of poor patient outcomes and thus may lead to the appropriate selection of adjuvant therapies at earlier UCC stages, which could improve patient prognosis. PMID:27895761

Characterization of the expression and clinical features of epidermal growth factor receptor and vascular endothelial growth factor receptor-2 in esophageal carcinoma

PubMed Central

NIYAZ, MADINIYAT; ANWER, JURAT; LIU, HUI; ZHANG, LIWEI; SHAYHEDIN, ILYAR; AWUT, IDIRIS

2015-01-01

The present study aimed to understand the expression characteristics of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor-2 (VEGFR-2) in individuals of Uygur, Han and Kazak ethnicity with esophageal carcinoma in Xinjiang (China) and their interrelation analysis, and to investigate the expression differences in these genes between esophageal carcinoma and pericarcinoma tissue samples, and between the three ethnic groups. The expression levels of EGFR and VEGFR-2 from 119 pairs of esophageal carcinoma tissue and corresponding pericarcinoma tissue from Uygur, Han and Kazak patients with esophageal carcinoma were detected by immunohistochemistry following surgical resection, and an additional five carcinoma in situ specimens were also tested. The relative expression was analyzed among the ethnic groups and clinicopathological parameters. The positive rate of EGFR in esophageal carcinoma tissue from patients of Uygur, Han and Kazak heritage was 70.73, 68.42 and 67.5%, respectively. For VEGFR-2 the positive rate was 73.17, 68.42 and 67.5%, respectively. No significant difference was detected in their expression between the three ethnic groups (P>0.05); however, EGFR and VEGFR-2 overexpression were correlated with lymph node metastasis (P<0.05). VEGF expression was also correlated with the expression of VEGFR-2 in esophageal carcinoma tissues. EGFR was positive in carcinoma in situ samples, while VEGFR-2 was negative. The overexpression of EGFR is therefore an early event and may have a significant role in the progression of esophageal carcinoma pathogenesis. EGFR overexpression may correlate with the expression of VEGFR-2 in esophageal cancer. These results may aid the early diagnosis of esophageal cancer, and the development of individual target treatment in the future. PMID:26788193

Human telomerase reverse transcriptase regulates vascular endothelial growth factor expression via human papillomavirus oncogene E7 in HPV-18-positive cervical cancer cells.

PubMed

Li, Fang; Cui, Jinquan

2015-07-01

Human papillomavirus (HPV) infection induces chronic and precancerous lesions and results in invasive cervical cancer. Human telomerase as well as inflammatory and angiogenic factors such as telomerase reverse transcriptase (hTERT) or vascular endothelial growth factor (VEGF) could play a role in regulating HPV-induced cervical cancer. This study investigated underlying molecular events in HPV-induced HPV-positive cervical cancer through hTERT and VEGF in vitro. Expressions of hTERT, a rate-limiting subunit of telomerase, and VEGF mRNA and proteins were, respectively, assessed by qRT-PCR, ELISA, and TRAP-ELISA in HPV-positive tissue samples and cervical cancer cell lines. To assess hTERT and VEGF secretion, hTERT overexpression and knockdown were conducted in HPV-18-positive Hela cells by hTERT cDNA and shRNA transfection, respectively. Then, the effect of HPV E6 and E7 on VEGF expressions was assessed in HPV-negative cervical cancer cells. Data have shown that VEGF expression levels are associated with hTERT expressions and telomerase activity in HPV-positive cervical cancer tissues and cells. Knockdown of hTERT expression down-regulated VEGF expressions, whereas overexpression of hTERT up-regulated VEGF expressions in HPV-18-positive Hela cells. Furthermore, HPV E7 oncoprotein was necessary for hTERT to up-regulate VEGF expressions in HPV-negative cervical cancer cells. Data from this current study indicate that HPV oncoproteins up-regulated hTERT and telomerase activity and in turn promoted VEGF expressions, which could be a key mechanism for HPV-induced cervical cancer development and progression.

REGγ regulates ERα degradation via ubiquitin–proteasome pathway in breast cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chai, Fan; Liang, Yan; Bi, Jiong

2015-01-02

Highlights: • High expression of REGγ is correlated with ERα status and poor clinical features. • Cell growth, mobility and invasion are significantly impaired by REGγ knockdown. • REGγ indirectly regulates ERα protein expression. - Abstract: REGγ is a proteasome coactivator which regulates proteolytic activity in eukaryotic cells. Abundant lines of evidence have showed that REGγ is over expressed in a number of human carcinomas. However, its precise role in the pathogenesis of cancer is still unclear. In this study, by examining 200 human breast cancer specimens, we demonstrated that REGγ was highly expressed in breast cancers, and the expressionmore » of REGγ was positively correlated with breast cancer patient estrogen receptor alpha (ERα) status. Moreover, the expression of REGγ was found positively associated with poor clinical features and low survival rates in ERα positive breast cancer patients. Further cell culture studies using MCF7 and BT474 breast cancer cell lines showed that cell proliferation, motility, and invasion capacities were decreased significantly by REGγ knockdown. Lastly, we demonstrated that REGγ indirectly regulates the degradation of ERα protein via ubiquitin–proteasome pathway. In conclusion, our findings provide the evidence that REGγ expression was positively correlated with ERα status and poor clinical prognosis in ERα positive breast cancer patients. As well, we disclose a new connection between the two molecules that are both highly expressed in most breast cancer cases.« less

Clinicopathological Implications of Human Papilloma Virus (HPV) L1 Capsid Protein Immunoreactivity in HPV16-Positive Cervical Cytology

PubMed Central

Lee, Sung-Jong; Lee, Ah-Won; Kang, Chang-Suk; Park, Jong-Sup; Park, Dong-Choon; Ki, Eun-Young; Lee, Keun-Ho; Yoon, Joo-Hee; Hur, Soo-Young; Kim, Tae-Jung

2014-01-01

Background: The objective of this study was to investigate the expression of human papilloma virus (HPV) L1 capsid protein in abnormal cervical cytology with HPV16 infection and analyze its association with cervical histopathology in Korean women. Material and Methods: We performed immunocytochemistry for HPV L1 in 475 abnormal cervical cytology samples from patients with HPV16 infections using the Cytoactiv® HPV L1 screening set. We investigated the expression of HPV L1 in cervical cytology samples and compared it with the results of histopathological examination of surgical specimens. Results: Of a total of 475 cases, 188 (39.6%) were immunocytochemically positive and 287 (60.4%) negative for HPV L1. The immunocytochemical expression rates of HPV L1 in atypical squamous cells of unknown significance (ASCUS), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), and cancer were 21.8%, 59.7%, 19.1%, and 0.0%, respectively. LSIL exhibited the highest rate of HPV L1 positivity. Of a total of 475 cases, the multiple-type HPV infection rate, including HPV16, in HPV L1-negative cytology samples was 27.5%, which was significantly higher than that in HPV L1-positive cytology samples (p = 0.037). The absence of HPV L1 expression in ASCUS and LSIL was significantly associated with high-grade (≥cervical intraepithelial neoplasia [CIN] 2) than low-grade (≤CIN1) histopathology diagnoses (p < 0.05), but was not significantly different between HPV16 single and multiple-type HPV infections (p > 0.05). On the other hand, among 188 HPV L1-positive cases, 30.6% of multiple-type HPV infections showed high-grade histopathology diagnoses (≥CIN3), significantly higher than the percentage of HPV16 single infections (8.6%) (p = 0.0004) Conclusions: Our study demonstrates that the expression of HPV L1 is low in advanced dysplasia. Furthermore, the absence of HPV L1 in HPV16-positive low-grade cytology (i.e., ASCUS and LSIL) is strongly associated with high-grade histopathology diagnoses. The multiplicity of HPV infections may have an important role in high-grade histopathology diagnoses (≥CIN3) in HPV L1-positive cases. PMID:24396289

When does Subliminal Affective Image Priming Influence the Ability of Schizophrenic Patients to Perceive Face Emotions?

PubMed Central

Vaina, Lucia M.; Rana, Kunjan D.; Cotos, Ionela; Li-Yang, Chen; Huang, Melissa A.; Podea, Delia

2014-01-01

Background Deficits in face emotion perception are among the most pervasive aspects of schizophrenia impairments which strongly affects interpersonal communication and social skills. Material/Methods Schizophrenic patients (PSZ) and healthy control subjects (HCS) performed 2 psychophysical tasks. One, the SAFFIMAP test, was designed to determine the impact of subliminally presented affective or neutral images on the accuracy of face-expression (angry or neutral) perception. In the second test, FEP, subjects saw pictures of face-expression and were asked to rate them as angry, happy, or neutral. The following clinical scales were used to determine the acute symptoms in PSZ: Positive and Negative Syndrome (PANSS), Young Mania Rating (YMRS), Hamilton Depression (HAM-D), and Hamilton Anxiety (HAM-A). Results On the SAFFIMAP test, different from the HCS group, the PSZ group tended to categorize the neutral expression of test faces as angry and their response to the test-face expression was not influenced by the affective content of the primes. In PSZ, the PANSS-positive score was significantly correlated with correct perception of angry faces for aggressive or pleasant primes. YMRS scores were strongly correlated with PSZ’s tendency to recognize angry face expressions when the prime was a pleasant or a neutral image. The HAM-D score was positively correlated with categorizing the test-faces as neutral, regardless of the affective content of the prime or of the test-face expression (angry or neutral). Conclusions Despite its exploratory nature, this study provides the first evidence that conscious perception and categorization of facial emotions (neutral or angry) in PSZ is directly affected by their positive or negative symptoms of the disease as defined by their individual scores on the clinical diagnostic scales. PMID:25537115

When does subliminal affective image priming influence the ability of schizophrenic patients to perceive face emotions?

PubMed

Vaina, Lucia Maria; Rana, Kunjan D; Cotos, Ionela; Li-Yang, Chen; Huang, Melissa A; Podea, Delia

2014-12-24

Deficits in face emotion perception are among the most pervasive aspects of schizophrenia impairments which strongly affects interpersonal communication and social skills. Schizophrenic patients (PSZ) and healthy control subjects (HCS) performed 2 psychophysical tasks. One, the SAFFIMAP test, was designed to determine the impact of subliminally presented affective or neutral images on the accuracy of face-expression (angry or neutral) perception. In the second test, FEP, subjects saw pictures of face-expression and were asked to rate them as angry, happy, or neutral. The following clinical scales were used to determine the acute symptoms in PSZ: Positive and Negative Syndrome (PANSS), Young Mania Rating (YMRS), Hamilton Depression (HAM-D), and Hamilton Anxiety (HAM-A). On the SAFFIMAP test, different from the HCS group, the PSZ group tended to categorize the neutral expression of test faces as angry and their response to the test-face expression was not influenced by the affective content of the primes. In PSZ, the PANSS-positive score was significantly correlated with correct perception of angry faces for aggressive or pleasant primes. YMRS scores were strongly correlated with PSZ's tendency to recognize angry face expressions when the prime was a pleasant or a neutral image. The HAM-D score was positively correlated with categorizing the test-faces as neutral, regardless of the affective content of the prime or of the test-face expression (angry or neutral). Despite its exploratory nature, this study provides the first evidence that conscious perception and categorization of facial emotions (neutral or angry) in PSZ is directly affected by their positive or negative symptoms of the disease as defined by their individual scores on the clinical diagnostic scales.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gabrielson, Marike; Reizer, Edwin; Stål, Olle

An increasing body of evidence is pointing towards mitochondrial regulation of the cell cycle. In a previous study of HER2-positive tumours we could demonstrate a common loss in the gene encoding for the mitochondrial transporter SLC25A43 and also a significant relation between SLC25A43 protein expression and S-phase fraction. Here, we investigated the consequence of suppressed SLC25A43 expression on cell cycle progression and proliferation in breast epithelial cells. In the present study, we suppressed SLC25A43 using siRNA in immortalised non-cancerous breast epithelial MCF10A cells and HER2-positive breast cancer cells BT-474. Viability, apoptosis, cell proliferation rate, cell cycle phase distribution, and nuclearmore » Ki-67 and p21, were assessed by flow cytometry. Cell cycle related gene expressions were analysed using real-time PCR. We found that SLC25A43 knockdown in MCF10A cells significantly inhibited cell cycle progression during G{sub 1}-to-S transition, thus significantly reducing the proliferation rate and fraction of Ki-67 positive MCF10A cells. In contrast, suppressed SLC25A43 expression in BT-474 cells resulted in a significantly increased proliferation rate together with an enhanced G{sub 1}-to-S transition. This was reflected by an increased fraction of Ki-67 positive cells and reduced level of nuclear p21. In line with our previous results, we show a role for SLC25A43 as a regulator of cell cycle progression and proliferation through a putative mitochondrial checkpoint. These novel data further strengthen the connection between mitochondrial function and the cell cycle, both in non-malignant and in cancer cells. - Highlights: • Proposed cell cycle regulation through the mitochondrial transporter SLC25A43. • SLC25A43 alters cell proliferation rate and cell cycle progression. • Suppressed SLC25A43 influences transcription of cell cycle regulatory genes.« less

Rate of Amino Acid Substitution Is Influenced by the Degree and Conservation of Male-Biased Transcription Over 50 Myr of Drosophila Evolution

PubMed Central

Grath, Sonja; Parsch, John

2012-01-01

Sex-biased gene expression (i.e., the differential expression of genes between males and females) is common among sexually reproducing species. However, genes often differ in their sex-bias classification or degree of sex bias between species. There is also an unequal distribution of sex-biased genes (especially male-biased genes) between the X chromosome and the autosomes. We used whole-genome expression data and evolutionary rate estimates for two different Drosophilid lineages, melanogaster and obscura, spanning an evolutionary time scale of around 50 Myr to investigate the influence of sex-biased gene expression and chromosomal location on the rate of molecular evolution. In both lineages, the rate of protein evolution correlated positively with the male/female expression ratio. Genes with highly male-biased expression, genes expressed specifically in male reproductive tissues, and genes with conserved male-biased expression over long evolutionary time scales showed the fastest rates of evolution. An analysis of sex-biased gene evolution in both lineages revealed evidence for a “fast-X” effect in which the rate of evolution was greater for X-linked than for autosomal genes. This pattern was particularly pronounced for male-biased genes. Genes located on the obscura “neo-X” chromosome, which originated from a recent X-autosome fusion, showed rates of evolution that were intermediate between genes located on the ancestral X-chromosome and the autosomes. This suggests that the shift to X-linkage led to an increase in the rate of molecular evolution. PMID:22321769

Expression of macrophage migration-inhibitory factor in duodenal ulcer and its relation to Helicobacter pylori infection.

PubMed

Yu, X H; Zhang, Q; Yang, X P; Yang, W; Dai, F; Qian, Z; Wang, Z L; Wu, C F; Zhao, H Z; Wang, G H

2015-10-30

The aim of this study was to examine the expression of macrophage migration-inhibitory factor (MIF) in duodenal ulcer epithelial cells and its relation to Helicobacter pylori (Hp) infection, and to discuss the pathogenic roles of MIF expression and Hp infection in duodenal ulcer. MIF protein and mRNA expression was examined in samples from patients with duodenal ulcer with and without Hp infection (N = 40 each, experimental group), and in normal duodenal bulb mucosal tissue (N = 40, control group) using immunohistochemistry and in situ hybridization. Patients without Hp infection received routine treatment, and treatment was provided to the patients positive for Hp to eradicate Hp infection. Hp and MIF expression levels before treatment and after the ulcer had been cured were compared. The positive rates of MIF protein and mRNA in patients with Hp infection before treatment were 67.5 and 65%, respectively, and were 18.9 and 21.6% in the 37 patients from whom Hp was eliminated. These were statistically different both before and after treatment compared with controls (P < 0.05). In the patients without Hp infection, the positive rates of MIF protein and mRNA expression before (45 and 47.5%, respectively) and after (32.5 and 30%) treatment were not significantly different (P > 0.05). The results of this study suggested that MIF is related to the development of duodenal ulcer, and that the presence of Hp is closely related with the expression of MIF in the duodenal mucosa and the development of duodenal ulcer.

Negative argininosuccinate synthetase expression in melanoma tumours may predict clinical benefit from arginine-depleting therapy with pegylated arginine deiminase

PubMed Central

Feun, L G; Marini, A; Walker, G; Elgart, G; Moffat, F; Rodgers, S E; Wu, C J; You, M; Wangpaichitr, M; Kuo, M T; Sisson, W; Jungbluth, A A; Bomalaski, J; Savaraj, N

2012-01-01

Background: Arginine-depleting therapy with pegylated arginine deiminase (ADI-PEG20) was reported to have activity in advanced melanoma in early phase I–II trial, and clinical trials are currently underway in other cancers. However, the optimal patient population who benefit from this treatment is unknown. Methods: Advanced melanoma patients with accessible tumours had biopsy performed before the start of treatment with ADI-PEG20 and at the time of progression or relapse when amenable to determine whether argininosuccinate synthetase (ASS) expression in tumour was predictive of response to ADI-PEG20. Results: Twenty-seven of thirty-eight patients treated had melanoma tumours assessable for ASS staining before treatment. Clinical benefit rate (CBR) and longer time to progression were associated with negative expression of tumour ASS. Only 1 of 10 patients with ASS-positive tumours (ASS+) had stable disease, whereas 4 of 17 (24%) had partial response and 5 had stable disease, when ASS expression was negative (ASS−), giving CBR rates of 52.9 vs 10%, P=0.041. Two responding patients with negative ASS expression before therapy had rebiopsy after tumour progression and the ASS expression became positive. The survival of ASS− patients receiving at least four doses at 320 IU m−2 was significantly better than the ASS+ group at 26.5 vs 8.5 months, P=0.024. Conclusion: ADI-PEG20 is safe and the drug is only efficacious in melanoma patients whose tumour has negative ASS expression. Argininosuccinate synthetase tumour positivity is associated with drug resistance and tumour progression. PMID:22472884

Detecting differentially expressed genes in heterogeneous diseases using half Student's t-test.

PubMed

Hsu, Chun-Lun; Lee, Wen-Chung

2010-12-01

Microarray technology provides information about hundreds and thousands of gene-expression data in a single experiment. To search for disease-related genes, researchers test for those genes that are differentially expressed between the case subjects and the control subjects. The authors propose a new test, the 'half Student's t-test', specifically for detecting differentially expressed genes in heterogeneous diseases. Monte-Carlo simulation shows that the test maintains the nominal α level quite well for both normal and non-normal distributions. Power of the half Student's t is higher than that of the conventional 'pooled' Student's t when there is heterogeneity in the disease under study. The power gain by using the half Student's t can reach ∼10% when the standard deviation of the case group is 50% larger than that of the control group. Application to a colon cancer data reveals that when the false discovery rate (FDR) is controlled at 0.05, the half Student's t can detect 344 differentially expressed genes, whereas the pooled Student's t can detect only 65 genes. Or alternatively, if only 50 genes are to be selected, the FDR for the pooled Student's t has to be set at 0.0320 (false positive rate of ∼3%), but for the half Student's t, it can be at as low as 0.0001 (false positive rate of about one per ten thousands). The half Student's t-test is to be recommended for the detection of differentially expressed genes in heterogeneous diseases.

The tell-tale: what do heart rate; skin temperature and skin conductance reveal about emotions of people with severe and profound intellectual disabilities?

PubMed

Vos, Pieter; De Cock, Paul; Munde, Vera; Petry, Katja; Van Den Noortgate, Wim; Maes, Bea

2012-01-01

Identifying emotions in people with severe and profound intellectual disabilities is a difficult challenge. Since self-reports are not available, behaviour is the most used source of information. Given the limitations and caveats associated with using behaviour as the sole source of information about their emotions, it is important to supplement behavioural information with information from another source. As it is accepted that emotions consist of language, behaviour and physiology, in this article we investigated if physiology could give information about the emotions of people with severe and profound intellectual disabilities. To this aim we tested hypotheses derived from the motivational model of Bradley, Codispoti, Cuthbert, and Lang (2001) about the relation between heart rate and the valence of emotions and between heart rate, skin conductance and skin temperature and behavioural expressions of emotions of people with severe and profound intellectual disability. We presented 27 participants with 4 staff-selected negative and 4 staff-selected positive stimuli. The situations were videotaped and their heart rate, skin conductance and skin temperature was measured. Each behaviour of the participant was coded using the observational method developed by Petry and Maes (2006). As hypothesized, we found a lower heart rate when participants were presented with negative stimuli than when they were presented with positive stimuli in the first 6s of stimuli presentation. Their skin temperature was higher for the expression of low intensity negative emotions compared to the expression of low intensity positive emotions. The results suggest that, as with people without disability, heart rate and skin temperature can give information about the emotions of persons with severe and profound ID. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Suppression of COX-2 protein to cell apoptosis in non-small cell lung cancer].

PubMed

Sun, Limei; Zhao, Yue; Wang, Lujian; Song, Min; Song, Jiye

2007-06-20

One of mechanisms of carcinogenesis is suppression of cell apoptosis which leads to accumulation of aberrant cells. The aim of this study is to investigate cell apoptosis and COX-2 protein expression in non-small cell lung cancer (NSCLC). Cell apoptosis, expression of COX-2 and microvessel density (MVD) were detcted in 111 NSCLC samples by TdT-mediated dUTP nick end labeling (TUNEL) technique and immunohistochemical staining. The positive rate of COX-2 protein expression was 67.6% (75/111), and there were 53 patients with high level cell apoptosis (47.7%). Expression of COX-2 protien was significantly related to TNM stages (P=0.025) and lymph node metastasis (P=0.018). The MVD in NSCLC tissues with positive COX-2 expression was significantly higher than that in negative expression ones (P=0.000). COX model showed that lymph node metastasis (P=0.006) and positive expression of COX-2 protein (P=0.000) were independent prognostic factors of NSCLC. The expression of COX-2 protein may suppress cell apoptosis of tumor, and it may serve as a potential marker of prognosis for NSCLC.

Efficient experimental design and analysis strategies for the detection of differential expression using RNA-Sequencing

PubMed Central

2012-01-01

Background RNA sequencing (RNA-Seq) has emerged as a powerful approach for the detection of differential gene expression with both high-throughput and high resolution capabilities possible depending upon the experimental design chosen. Multiplex experimental designs are now readily available, these can be utilised to increase the numbers of samples or replicates profiled at the cost of decreased sequencing depth generated per sample. These strategies impact on the power of the approach to accurately identify differential expression. This study presents a detailed analysis of the power to detect differential expression in a range of scenarios including simulated null and differential expression distributions with varying numbers of biological or technical replicates, sequencing depths and analysis methods. Results Differential and non-differential expression datasets were simulated using a combination of negative binomial and exponential distributions derived from real RNA-Seq data. These datasets were used to evaluate the performance of three commonly used differential expression analysis algorithms and to quantify the changes in power with respect to true and false positive rates when simulating variations in sequencing depth, biological replication and multiplex experimental design choices. Conclusions This work quantitatively explores comparisons between contemporary analysis tools and experimental design choices for the detection of differential expression using RNA-Seq. We found that the DESeq algorithm performs more conservatively than edgeR and NBPSeq. With regard to testing of various experimental designs, this work strongly suggests that greater power is gained through the use of biological replicates relative to library (technical) replicates and sequencing depth. Strikingly, sequencing depth could be reduced as low as 15% without substantial impacts on false positive or true positive rates. PMID:22985019

Efficient experimental design and analysis strategies for the detection of differential expression using RNA-Sequencing.

PubMed

Robles, José A; Qureshi, Sumaira E; Stephen, Stuart J; Wilson, Susan R; Burden, Conrad J; Taylor, Jennifer M

2012-09-17

RNA sequencing (RNA-Seq) has emerged as a powerful approach for the detection of differential gene expression with both high-throughput and high resolution capabilities possible depending upon the experimental design chosen. Multiplex experimental designs are now readily available, these can be utilised to increase the numbers of samples or replicates profiled at the cost of decreased sequencing depth generated per sample. These strategies impact on the power of the approach to accurately identify differential expression. This study presents a detailed analysis of the power to detect differential expression in a range of scenarios including simulated null and differential expression distributions with varying numbers of biological or technical replicates, sequencing depths and analysis methods. Differential and non-differential expression datasets were simulated using a combination of negative binomial and exponential distributions derived from real RNA-Seq data. These datasets were used to evaluate the performance of three commonly used differential expression analysis algorithms and to quantify the changes in power with respect to true and false positive rates when simulating variations in sequencing depth, biological replication and multiplex experimental design choices. This work quantitatively explores comparisons between contemporary analysis tools and experimental design choices for the detection of differential expression using RNA-Seq. We found that the DESeq algorithm performs more conservatively than edgeR and NBPSeq. With regard to testing of various experimental designs, this work strongly suggests that greater power is gained through the use of biological replicates relative to library (technical) replicates and sequencing depth. Strikingly, sequencing depth could be reduced as low as 15% without substantial impacts on false positive or true positive rates.

Comprehensive Evaluation of Programmed Death-Ligand 1 Expression in Primary and Metastatic Prostate Cancer.

PubMed

Haffner, Michael C; Guner, Gunes; Taheri, Diana; Netto, George J; Palsgrove, Doreen N; Zheng, Qizhi; Guedes, Liana Benevides; Kim, Kunhwa; Tsai, Harrison; Esopi, David M; Lotan, Tamara L; Sharma, Rajni; Meeker, Alan K; Chinnaiyan, Arul M; Nelson, William G; Yegnasubramanian, Srinivasan; Luo, Jun; Mehra, Rohit; Antonarakis, Emmanuel S; Drake, Charles G; De Marzo, Angelo M

2018-06-01

Antibodies targeting the programmed cell death protein 1/programmed death-ligand 1 (PD-L1) interaction have shown clinical activity in multiple cancer types. PD-L1 protein expression is a clinically validated predictive biomarker of response for such therapies. Prior studies evaluating the expression of PD-L1 in primary prostate cancers have reported highly variable rates of PD-L1 positivity. In addition, limited data exist on PD-L1 expression in metastatic castrate-resistant prostate cancer (mCRPC). Here, we determined PD-L1 protein expression by immunohistochemistry using a validated PD-L1-specific antibody (SP263) in a large and representative cohort of primary prostate cancers and prostate cancer metastases. The study included 539 primary prostate cancers comprising 508 acinar adenocarcinomas, 24 prostatic duct adenocarcinomas, 7 small-cell carcinomas, and a total of 57 cases of mCRPC. PD-L1 positivity was low in primary acinar adenocarcinoma, with only 7.7% of cases showing detectable PD-L1 staining. Increased levels of PD-L1 expression were noted in 42.9% of small-cell carcinomas. In mCRPC, 31.6% of cases showed PD-L1-specific immunoreactivity. In conclusion, in this comprehensive evaluation of PD-L1 expression in prostate cancer, PD-L1 expression is rare in primary prostate cancers, but increased rates of PD-L1 positivity were observed in mCRPC. These results will be important for the future clinical development of programmed cell death protein 1/PD-L1-targeting therapies in prostate cancer. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Impact of IGF-1, IGF-1R, and IGFBP-3 promoter methylation on the risk and prognosis of esophageal carcinoma.

PubMed

Ye, Peng; Qu, Chang-Fa; Hu, Xue-Lin

2016-05-01

The aim of this study is to investigate IGF-1, IGF-1R, and IGFBP-3 methylations in esophageal carcinoma (EC) patients and their relationship with the development and prognosis of EC. This study population consisted of 264 patients (case group) whom EC radical resection was performed and 283 healthy individuals (control group). Methylation-specific PCR (MSP) detected the methylation status of IGF-1, IGF-1R, and IGFBP-3 in the peripheral blood in both groups. The expressions of IGF-1, IGF-1R, and IGFBP-3 in EC and adjacent normal tissues were detected by immunohistochemistry (IHC). The methylation rates of IGF-1, IGF-1R, IGFBP3, and IGF-1 + IGF1R + IGFBP3 in the case group were higher than those in the control group (all P < 0.05). Additionally, there were statistical significances for the methylation rates of IGF-1, IGF-1R, IGFBP3, and IGF-1 + IGF1R + IGFBP3 IGF-1 among patients of different clinicopathological features (all P < 0.05). The positive expression rates of IGF-1 and IGF-1R in EC were significantly higher than those in adjacent normal tissues (both P < 0.001), and the rate of IGFBP-3 in EC was significantly lower than that in adjacent normal tissues (P < 0.05). Correlation analysis showed that IGF-1 and IGF1R gene promoter methylation was positively correlated with the positive expressions of IGF-1 (r = 0.139, P = 0.024) and IGF-1R (r = 0.135, P = 0.028), while the IGFBP3 methylation was negatively correlated with the positive expression of IGFBP3 (r = -0.133, P = 0.031). The positive expressions of IGF-1, IGF-1R, and IGFBP-3 were related to different clinicopathological features (all P < 0.05). Cox multivariate analysis results showed that methylation status of IGF-1, IGF-1R, and IGF-1 + IGF1R + IGFBP3 ; expressions of IGF-1 and IGF-1R protein; infiltration depth; and lymph node metastasis (LNM) were independent factors of EC prognosis. Our study demonstrated that methylation of IGF-1, IGF1R, IGFBP3, and IGF-1 + IGF1R + IGFBP3 was closely linked with the occurrence of EC and patients' clinicopathological features. Besides, the methylation status of the target genes and the expressions of IGF-1 and IGF-1R protein were independent factors of EC prognosis, which could provide a direction for the prognosis and treatment of EC.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Fujin; Department of Urinary Surgery, Huai'an Hospital to Xuzhou Medical University, Huai'an, Jiangsu; Ma, Song

Lactate dehydrogenase-A(LDH-A) is an important rate-limiting enzyme in the Warburg effect. Survival analysis indicated poor clinical outcomes in MIBC with high LDH-A expression. The results of in vitro experiment indicated that LDH-A promotes MIBC cells proliferation, invasion and migration. The positive relationship between LDH-A expression and CSC/EMT markers was confirmed both in invasive bladder cell line and in 136 MIBC specimens. Thus, we conclude that LDH-A may be a promising target for MIBC. - Highlights: • Survival analysis indicated poor clinical outcomes in MIBC with high LDH-A expression. • IHC analysis of 136 MIBC specimens revealed increased LDH-A is correlated withmore » positive Oct4 and negative E-cadherin. • In vitro experiments demonstrated LDH-A promotes MIBC progression by positive regulation of EMT/CSC.« less

B7-H3 expression and its correlation with clinicopathologic features, angiogenesis, and prognosis in intrahepatic cholangiocarcinoma.

PubMed

Cheng, Rui; Chen, Yongqin; Zhou, Haohui; Wang, Bi; Du, Qiang; Chen, Yanling

2018-05-01

This study was designed to explore the expression of B7-H3 in human intrahepatic cholangiocarcinoma (ICC) and its association with the clinicopathologic factors. In the current study, the expression of B7-H3 in 45 patients with intrahepatic cholangiocarcinoma and 8 patients with hepatolithiasis was analyzed by immunohistochemistry, which revealed that B7-H3 was not expressed in hepatolithiatic tissues, but positively expressed in 57.8% (26/45) of the ICC cases. The expression of B7-H3 was significantly associated with lymph node metastases and venous invasion. A positive correlation was also observed between the expression of B7-H3 and MVD, an index for tumor angiogenesis. Further survival analysis indicated that patients with B7-H3 negative expression had higher overall survival (OS) and cancer-specific survival (CSS) rates than those with B7-H3 positive expression. Multivariate analysis revealed that B7-H3 expression was an independent prognostic indicator for poor OS and CSS of ICC patients. Our results suggest that B7-H3 may be a valuable biomarker in determining tumor progression and prognosis of intrahepatic cholangiocarcinoma. It is also a potential target for antivascular therapy of ICC. © 2018 APMIS. Published by John Wiley & Sons Ltd.

Selective modes determine evolutionary rates, gene compactness and expression patterns in Brassica.

PubMed

Guo, Yue; Liu, Jing; Zhang, Jiefu; Liu, Shengyi; Du, Jianchang

2017-07-01

It has been well documented that most nuclear protein-coding genes in organisms can be classified into two categories: positively selected genes (PSGs) and negatively selected genes (NSGs). The characteristics and evolutionary fates of different types of genes, however, have been poorly understood. In this study, the rates of nonsynonymous substitution (K a ) and the rates of synonymous substitution (K s ) were investigated by comparing the orthologs between the two sequenced Brassica species, Brassica rapa and Brassica oleracea, and the evolutionary rates, gene structures, expression patterns, and codon bias were compared between PSGs and NSGs. The resulting data show that PSGs have higher protein evolutionary rates, lower synonymous substitution rates, shorter gene length, fewer exons, higher functional specificity, lower expression level, higher tissue-specific expression and stronger codon bias than NSGs. Although the quantities and values are different, the relative features of PSGs and NSGs have been largely verified in the model species Arabidopsis. These data suggest that PSGs and NSGs differ not only under selective pressure (K a /K s ), but also in their evolutionary, structural and functional properties, indicating that selective modes may serve as a determinant factor for measuring evolutionary rates, gene compactness and expression patterns in Brassica. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

[Expression and correlation of Fra-1 and HMGA1 in laryngeal squamous cell carcinoma].

PubMed

Zhang, Y L; Song, X F; Duan, Y J; Zhao, R L

2017-12-07

Objective: To investigate the expressions of Fra -1 and HMGA 1 in laryngeal squamous cell carcinoma and their correlation . Methods: Immunohistochemistry and reverse transcription-polymer chain reaction (RT-PCR) were used to detect the expressions of HMGA 1 and Fra -1 in laryngeal squamous carcinoma tissues in 47 cases and para - carcinoma tissues in 21 cases ( the First Hospital of Shijiazhuang ). The relationship between the gene expressions in carcinoma tissues and clinopathological parameters such as pathological grade, clinical stage, lymph metastasis, age and anatomic site and the relevance of the two gene expressions were analyzed . SPSS 13.0 software was used to analyze the data . Results: The positive expression rates of Fra-1 and HMGA1 proteins in laryngeal squamous cancer tissue were 48.9% and 53.2%, which were respectively higher than the rates of 19.0% for Fra-1 (χ(2)=5.416, P <0.05) and of 23.8% for HMGA1 (χ(2)=5.083, P <0.05) in adjacent tissues. The expression of Fra -1 gene was correlation with pathological grade, clinical stage and lymph metastasis (t values were -1.079, -1.066 and -1.067, all P<0.05), but not with age and anatomic site (t values were -1.068 and -1.054, both P>0.05). The expression of HMGA 1 gene was correlation with pathological grade, clinical stage, lymph metastasis and age (t values were -1.112, -1.065, -1.009 and -1.066, all P<0.05), but not with anatomic site (t=-1.036, P>0.05). The expressions of Fra -1 and HMGA 1 gene were positively correlation (r=0.672, P<0.05). Conclusions: In laryngeal squamous cancer, Fra -1 and HMGA 1 are excessive expression, with a positive correlation between the expressions of both genes .

Prognostic significance of p53 immunohistochemical expression in adenoid cystic carcinoma of the salivary glands: a meta-analysis

PubMed Central

Zheng, Chuanming; Wang, Jiafeng; Ge, Minghua

2017-01-01

Adenoid cystic carcinoma of salivary glands is a rare adenocarcinoma and has been placed in “high-risk” category as poor long-term prognosis. The purpose of this study was to investigate p53 protein expression in adenoid cystic carcinoma of salivary glands and its correlation with clinicopathological parameters and prognosis. Literatures were searched from PubMed, Embase, Cochrane Library and Web of Science, which investigated the relationships between p53 expression and pathological type, clinical stage, local recurrence, metastasis, nerve infiltration and overall survival. A total of 1,608 patients from 36 studies were included in the analysis. The results showed that p53-postive expression rate was 49% in adenoid cystic carcinoma of salivary glands (OR=10.34, 95%CI: 4.93-21.71, P < 0.0001). The p53-postive expression was closely related to tumor types (OR=0.30, 95%CI: 0.14-0.65, P < 0.0001). The tumor with solid histological subtype had a strong positive correlation with p53 expression. The combined analysis revealed that the p53-positive expression rate among patients in T1and T2 stage was 41.4%, compared to 53.2% among those in T3 and T4 stage. However, there was no significant correlation between tumor stage and p53 expression (OR=0.47, 95% CI: 0.17-1.29, P = 0.14). Besides, compared to patients with p53-negative expression, those with p53-positive expression had a greater chance of developing metastasis, local recurrence and nerve infiltration as well as poorer 5-year overall survival (P < 0.01). In conclusion, the p53 expression is related to the survival of adenoid cystic carcinoma of salivary glands. It can be considered as the auxiliary detection index in treatment and prognosis of adenoid cystic carcinoma of salivary glands. PMID:28206977

Prognostic significance of p53 immunohistochemical expression in adenoid cystic carcinoma of the salivary glands: a meta-analysis.

PubMed

Li, Qinglin; Huang, Ping; Zheng, Chuanming; Wang, Jiafeng; Ge, Minghua

2017-04-25

Adenoid cystic carcinoma of salivary glands is a rare adenocarcinoma and has been placed in "high-risk" category as poor long-term prognosis. The purpose of this study was to investigate p53 protein expression in adenoid cystic carcinoma of salivary glands and its correlation with clinicopathological parameters and prognosis. Literatures were searched from PubMed, Embase, Cochrane Library and Web of Science, which investigated the relationships between p53 expression and pathological type, clinical stage, local recurrence, metastasis, nerve infiltration and overall survival. A total of 1,608 patients from 36 studies were included in the analysis. The results showed that p53-postive expression rate was 49% in adenoid cystic carcinoma of salivary glands (OR=10.34, 95%CI: 4.93-21.71, P < 0.0001). The p53-postive expression was closely related to tumor types (OR=0.30, 95%CI: 0.14-0.65, P < 0.0001). The tumor with solid histological subtype had a strong positive correlation with p53 expression. The combined analysis revealed that the p53-positive expression rate among patients in T1and T2 stage was 41.4%, compared to 53.2% among those in T3 and T4 stage. However, there was no significant correlation between tumor stage and p53 expression (OR=0.47, 95% CI: 0.17-1.29, P = 0.14). Besides, compared to patients with p53-negative expression, those with p53-positive expression had a greater chance of developing metastasis, local recurrence and nerve infiltration as well as poorer 5-year overall survival (P < 0.01).In conclusion, the p53 expression is related to the survival of adenoid cystic carcinoma of salivary glands. It can be considered as the auxiliary detection index in treatment and prognosis of adenoid cystic carcinoma of salivary glands.

Identification of genes showing differential expression profile associated with growth rate in skeletal muscle tissue of Landrace weanling pig.

PubMed

Komatsu, Yuuta; Sukegawa, Shin; Yamashita, Mai; Katsuda, Naoki; Tong, Bin; Ohta, Takeshi; Kose, Hiroyuki; Yamada, Takahisa

2016-06-01

Suppression subtractive hybridization was used to identify genes showing differential expression profile associated with growth rate in skeletal muscle tissue of Landrace weanling pig. Two subtracted cDNA populations were generated from musculus longissimus muscle tissues of selected pigs with extreme expected breeding values at the age of 100 kg. Three upregulated genes (EEF1A2, TSG101 and TTN) and six downregulated genes (ATP5B, ATP5C1, COQ3, HADHA, MYH1 and MYH7) in pig with genetic propensity for higher growth rate were identified by sequence analysis of 12 differentially expressed clones selected by differential screening following the generation of the subtracted cDNA population. Real-time PCR analysis confirmed difference in expression profiles of the identified genes in musculus longissimus muscle tissues between the two Landrace weanling pig groups with divergent genetic propensity for growth rate. Further, differential expression of the identified genes except for the TTN was validated by Western blot analysis. Additionally, the eight genes other than the ATP5C1 colocalized with the same chromosomal positions as QTLs that have been previously identified for growth rate traits. Finally, the changes of expression predicted from gene function suggested association of upregulation of expression of the EEF1A2, TSG101 and TTN genes and downregulation of the ATP5B, ATP5C1, COQ3, HADHA, MYH1 and MYH7 gene expression with increased growth rate. The identified genes will provide an important insight in understanding the molecular mechanism underlying growth rate in Landrace pig breed.

[Expression of vascular endothelial growth factor and its significance in pulmonary bronchoalveolar carcinoma].

PubMed

Song, Weian; Li, Hui; Wang, Huasheng; Zhang, Weidong; Zhao, Xiaogang

2004-02-20

To study the relationship between the vascular endothelial growth factor (VEGF) and the clinicopathological characteristics of the patients with pulmonary bronchoalveolar carcinoma, and to research the possible role of VEGF in the malignant growth of pulmonary bronchoalveolar carcinoma. The expression of VEGF and MVD were detected in 38 pulmonary bronchoalveolar carcinoma and 20 normal lung tissues by immunohistochemical method. The positive rate of VEGF expression (73.68%,28/38) and MVD (63.81±19.26) in pulmonary bronchoalveolar carcinoma tissues were both remarkably higher than those in normal lung tissues (0, 18.44±6.53)( P < 0.005,P < 0.001). The positive rate of VEGF expression was significantly related to the size of tumor ( P < 0.05), lymphatic metastasis ( P < 0.025) and TNM stage ( P < 0.05), and so did the MVD ( P < 0.05, P < 0.05, P < 0.05). MVD was remarkably higher in VEGF (+) carcinoma tissues than that in VEGF (-) carcinoma tissues ( P < 0.05). VEGF correlates with the clinicopathological characteristics of pulmonary bronchoalveolar carcinoma. It may play an important role in the development of pulmonary bronchoalveolar carcinoma.

A Role for REM Sleep in Recalibrating the Sensitivity of the Human Brain to Specific Emotions

PubMed Central

Gujar, Ninad; McDonald, Steven Andrew; Nishida, Masaki

2011-01-01

Although the impact of sleep on cognitive function is increasingly well established, the role of sleep in modulating affective brain processes remains largely uncharacterized. Using a face recognition task, here we demonstrate an amplified reactivity to anger and fear emotions across the day, without sleep. However, an intervening nap blocked and even reversed this negative emotional reactivity to anger and fear while conversely enhancing ratings of positive (happy) expressions. Most interestingly, only those subjects who obtained rapid eye movement (REM) sleep displayed this remodulation of affective reactivity for the latter 2 emotion categories. Together, these results suggest that the evaluation of specific human emotions is not static across a daytime waking interval, showing a progressive reactivity toward threat-related negative expressions. However, an episode of sleep can reverse this predisposition, with REM sleep depotentiating negative reactivity toward fearful expressions while concomitantly facilitating recognition and ratings of reward-relevant positive expressions. These findings support the view that sleep, and specifically REM neurophysiology, may represent an important factor governing the optimal homeostasis of emotional brain regulation. PMID:20421251

CIP2A down regulation enhances the sensitivity of pancreatic cancer cells to gemcitabine.

PubMed

Xu, Peng; Yao, Jie; He, Jin; Zhao, Long; Wang, Xiaodong; Li, Zhennan; Qian, Jianjun

2016-03-22

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein which participates in inhibiting tumor apoptosis in pancreatic cancer cells. Using immunohistochemical staining, we investigated the expression of CIP2A protein in 72 cases of human pancreatic ductal adenocarcinoma (PDAC) tissue and 27 cases of adjacent normal pancreatic tissue. The positive rate of CIP2A protein expression in pancreatic cancer tissue was70.83 %, which was significantly higher than that in adjacent non- cancerous pancreatic tissue (11.11%). The expression of CIP2A was found to be correlated with TNM stage, but not correlated with age, gender, tumor location, smoking status, alcohol consumption, diabetes, high blood pressure, BMI, tumor size, lymph node metastasis or distant metastases. Kaplan- Meier survival analysis showed that patients with positive CIP2A protein expression had a lower overall survival rate than patients without CIP2A expression. COX regression analysis indicated that expression of CIP2A was an independent prognostic factor for pancreatic ductal adenocarcinoma. In addition, down-regulation of CIP2A inhibited cell proliferation and increased sensitivity to gemcitabine in pancreatic cancer cells by decreasing AKT signaling pathway. Our results indicated that down-regulation of CIP2A could be a novel therapeutic strategy for pancreatic cancer.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shim, Su Jung; Yang, Woo-Ick; Shin, Eunah

Purpose: To determine whether there are any differences in therapeutic response, patterns of systemic recurrence, and prognosis of patients with extranodal natural killer (NK)/T-cell lymphoma, nasal type, by the cyclooxygenase-2 (COX-2) expression. Patients and Methods: Thirty-four patients with Ann Arbor Stage I and II extranodal NK/T-cell lymphoma who underwent chemotherapy or radiotherapy, or both, were retrospectively reviewed. These patients were divided into two groups according to their immunohistochemical staining for COX-2 expressions: a COX-2-negative group (n = 10 patients) and a COX-2-positive group (n = 24 patients). The treatment response, patterns of treatment failure, and survival data for the patientsmore » were compared between the COX-2-positive and negative groups. Results: There was no significant difference in the clinical profiles between the COX-2-negative and COX-2-positive groups. All patients (100%) in the COX-2-negative group achieved complete response after initial treatment, whereas only 14 patients (58%) in the COX-2-positive group achieved complete response (p = 0.03). Compared with the patients in the COX-2-negative group, those in the COX-2-positive group had a significantly lower 2-year systemic recurrence-free survival rate (100% for the COX-2-negative group vs. 54% for the COX-2-positive group) (p = 0.02) and a decreased 5-year overall survival rate (70% for the COX-2-negative group vs. 32% for the COX-2-positive group) (p = 0.06). Conclusion: Cyclooxygenase-2 expression can serve as a predictive factor for poor treatment response, higher systemic recurrence, and unfavorable prognosis in patients with extranodal NK/T-cell lymphoma, nasal type.« less

Correlation between expression of cyclooxygenase-2 and angiogenesis in human gastric adenocarcinoma

PubMed Central

Li, Hong-Xia; Chang, Xin-Ming; Song, Zheng-Jun; He, Shui-Xiang

2003-01-01

AIM: To evaluate the expression of cyclooxygenase (COX-2) and the relationship with tumor angiogenesis and advancement in gastric adenocarcinoma. METHODS: Immunohistochemical stain was used for detecting the expression of COX-2 in 45 resected specimens of gastric adenocarcinoma; the monoclonal antibody against CD34 was used for displaying vascular endothelial cells, and microvascular density (MVD) was detected by counting of CD34-positive vascular endothelial cells. Paracancerous tissues were examined as control. RESULTS: Immunohistological staining with COX-2-specific polyclonal antibody showed cytoplasmic staining in the cancer cells, some atypical hyperplasia and intestinal metaplasia, as well as angiogenic vasculature present within the tumors and prexisting vasculature adjacent to cancer lesions. The rate of expression of COX-2 and MVD index in gastric cancers were significantly increased, compared with those in the paracancerous tissues (77.78 vs 33.33%, 58.13 ± 19.99 vs 24.02 ± 10.28, P < 0.01, P < 0.05, respectively). In 36 gastric carcinoma specimens with lymph node metastasis, the rate of COX-2 expression and MVD were higher than those in the specimens without metostasis (86.11 vs 44.44%, 58.60 ± 18.24 vs 43.54 ± 15.05, P < 0.05, P < 0.05, respectively). The rate of COX-2 expression and MVD in the specimens with invasive serosa were significantly higher than those in the specimens without invasion to serosa (87.88 vs 50.0%, 57.01 ± 18.79 vs 42.35 ± 14.65, P < 0.05, P < 0.05). Moreover, MVD in COX-2-positive specimens was higher than that in COX-2-negative specimens (61.29 ± 14.31 vs 45.38 ± 12.42, P < 0.05). COX-2 expression was positively correlated with MVD (r = 0.63, P < 0.05). CONCLUSION: COX-2 expression might correlate with the occurance and advancement of gastric carcinoma and is involved in tumor angiogenesis in gastric carcinoma. It is likely that COX-2 by inducing angiogenesis can be one of mechanisms which promotes invasion and metastasis of gastric carcinoma. It may become a new therapeutic target for anti-angiogenesis. PMID:12679908

Interpreting text messages with graphic facial expression by deaf and hearing people.

PubMed

Saegusa, Chihiro; Namatame, Miki; Watanabe, Katsumi

2015-01-01

In interpreting verbal messages, humans use not only verbal information but also non-verbal signals such as facial expression. For example, when a person says "yes" with a troubled face, what he or she really means appears ambiguous. In the present study, we examined how deaf and hearing people differ in perceiving real meanings in texts accompanied by representations of facial expression. Deaf and hearing participants were asked to imagine that the face presented on the computer monitor was asked a question from another person (e.g., do you like her?). They observed either a realistic or a schematic face with a different magnitude of positive or negative expression on a computer monitor. A balloon that contained either a positive or negative text response to the question appeared at the same time as the face. Then, participants rated how much the individual on the monitor really meant it (i.e., perceived earnestness), using a 7-point scale. Results showed that the facial expression significantly modulated the perceived earnestness. The influence of positive expression on negative text responses was relatively weaker than that of negative expression on positive responses (i.e., "no" tended to mean "no" irrespective of facial expression) for both participant groups. However, this asymmetrical effect was stronger in the hearing group. These results suggest that the contribution of facial expression in perceiving real meanings from text messages is qualitatively similar but quantitatively different between deaf and hearing people.

Phosphorus acquisition by citrate- and phytase-exuding Nicotiana tabacum plant mixtures depends on soil phosphorus availability and root intermingling.

PubMed

Giles, Courtney D; Richardson, Alan E; Cade-Menun, Barbara J; Mezeli, Malika M; Brown, Lawrie K; Menezes-Blackburn, Daniel; Darch, Tegan; Blackwell, Martin Sa; Shand, Charles A; Stutter, Marc I; Wendler, Renate; Cooper, Patricia; Lumsdon, David G; Wearing, Catherine; Zhang, Hao; Haygarth, Philip M; George, Timothy S

2018-03-02

Citrate and phytase root exudates contribute to improved phosphorus (P) acquisition efficiency in Nicotiana tabacum (tobacco) when both exudates are produced in a P deficient soil. To test the importance of root intermingling in the interaction of citrate and phytase exudates, Nicotiana tabacum plant-lines with constitutive expression of heterologous citrate (Cit) or fungal phytase (Phy) exudation traits were grown under two root treatments (roots separated or intermingled) and in two soils with contrasting soil P availability. Complementarity of plant mixtures varying in citrate efflux rate and mobility of the expressed phytase in soil was determined based on plant biomass and P accumulation. Soil P composition was evaluated using solution 31 P NMR spectroscopy. In the soil with limited available P, positive complementarity occurred in Cit+Phy mixtures with roots intermingled. Root separation eliminated positive interactions in mixtures expressing the less mobile phytase (Aspergillus niger PhyA) whereas positive complementarity persisted in mixtures that expressed the more mobile phytase (Peniophora lycii PhyA). Soils from Cit+Phy mixtures contained less inorganic P and more organic P compared to monocultures. Exudate-specific strategies for the acquisition of soil P were most effective in P-limited soil and depended on citrate efflux rate and the relative mobility of the expressed phytase in soil. Plant growth and soil P utilization in plant systems with complementary exudation strategies are expected to be greatest where exudates persist in soil and are expressed synchronously in space and time. This article is protected by copyright. All rights reserved.

Faster-X evolution of gene expression is driven by recessive adaptive cis-regulatory variation in Drosophila.

PubMed

Llopart, Ana

2018-05-01

The hemizygosity of the X (Z) chromosome fully exposes the fitness effects of mutations on that chromosome and has evolutionary consequences on the relative rates of evolution of X and autosomes. Specifically, several population genetics models predict increased rates of evolution in X-linked loci relative to autosomal loci. This prediction of faster-X evolution has been evaluated and confirmed for both protein coding sequences and gene expression. In the case of faster-X evolution for gene expression divergence, it is often assumed that variation in 5' noncoding sequences is associated with variation in transcript abundance between species but a formal, genomewide test of this hypothesis is still missing. Here, I use whole genome sequence data in Drosophila yakuba and D. santomea to evaluate this hypothesis and report positive correlations between sequence divergence at 5' noncoding sequences and gene expression divergence. I also examine polymorphism and divergence in 9,279 noncoding sequences located at the 5' end of annotated genes and detected multiple signals of positive selection. Notably, I used the traditional synonymous sites as neutral reference to test for adaptive evolution, but I also used bases 8-30 of introns <65 bp, which have been proposed to be a better neutral choice. X-linked genes with high degree of male-biased expression show the most extreme adaptive pattern at 5' noncoding regions, in agreement with faster-X evolution for gene expression divergence and a higher incidence of positively selected recessive mutations. © 2018 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

Prostate-specific membrane antigen in breast cancer: a comprehensive evaluation of expression and a case report of radionuclide therapy.

PubMed

Tolkach, Yuri; Gevensleben, Heidrun; Bundschuh, Ralph; Koyun, Aydan; Huber, Daniela; Kehrer, Christina; Hecking, Thomas; Keyver-Paik, Mignon-Denise; Kaiser, Christina; Ahmadzadehfar, Hojjat; Essler, Markus; Kuhn, Walther; Kristiansen, Glen

2018-06-01

Prostate-specific membrane antigen (PSMA), a protein product of the folate hydrolase 1 (FOLH1) gene, is gaining increasing acceptance as a target for positron emission tomography/computer tomography (PET/CT) imaging in patients with several cancer types, including breast cancer. So far, PSMA expression in breast cancer endothelia has not been sufficiently characterized. This study comprised 315 cases of invasive carcinoma of no special type (NST) and lobular breast cancer (median follow-up time 9.0 years). PSMA expression on tumor endothelia was detected by immunohistochemistry. Further, vascular mRNA expression of the FOLH1 gene (PSMA) was investigated in a cohort of patients with invasive breast cancer provided by The Cancer Genome Atlas (TCGA). Sixty percent of breast cancer cases exhibited PSMA-positive endothelia with higher expression rates in tumors of higher grade, NST subtype with Her2-positivity, and lack of hormone receptors. These findings were confirmed on mRNA expression levels. The highest PSMA rates were observed in triple-negative carcinomas (4.5 × higher than in other tumors). Further, a case of a patient with metastatic breast cancer showing PSMA expression in PET/CT imaging and undergoing PSMA radionuclide therapy is discussed in detail. This study provides a rationale for the further development of PSMA-targeted imaging in breast cancer, especially in triple-negative tumors.

Systematic identification of genes involved in divergent skeletal muscle growth rates of broiler and layer chickens.

PubMed

Zheng, Qi; Zhang, Yong; Chen, Ying; Yang, Ning; Wang, Xiu-Jie; Zhu, Dahai

2009-02-22

The genetic closeness and divergent muscle growth rates of broilers and layers make them great models for myogenesis study. In order to discover the molecular mechanisms determining the divergent muscle growth rates and muscle mass control in different chicken lines, we systematically identified differentially expressed genes between broiler and layer skeletal muscle cells during different developmental stages by microarray hybridization experiment. Taken together, 543 differentially expressed genes were identified between broilers and layers across different developmental stages. We found that differential regulation of slow-type muscle gene expression, satellite cell proliferation and differentiation, protein degradation rate and genes in some metabolic pathways could give great contributions to the divergent muscle growth rates of the two chicken lines. Interestingly, the expression profiles of a few differentially expressed genes were positively or negatively correlated with the growth rates of broilers and layers, indicating that those genes may function in regulating muscle growth during development. The multiple muscle cell growth regulatory processes identified by our study implied that complicated molecular networks involved in the regulation of chicken muscle growth. These findings will not only offer genetic information for identifying candidate genes for chicken breeding, but also provide new clues for deciphering mechanisms underlining muscle development in vertebrates.

Relaxation rates of gene expression kinetics reveal the feedback signs of autoregulatory gene networks

NASA Astrophysics Data System (ADS)

Jia, Chen; Qian, Hong; Chen, Min; Zhang, Michael Q.

2018-03-01

The transient response to a stimulus and subsequent recovery to a steady state are the fundamental characteristics of a living organism. Here we study the relaxation kinetics of autoregulatory gene networks based on the chemical master equation model of single-cell stochastic gene expression with nonlinear feedback regulation. We report a novel relation between the rate of relaxation, characterized by the spectral gap of the Markov model, and the feedback sign of the underlying gene circuit. When a network has no feedback, the relaxation rate is exactly the decaying rate of the protein. We further show that positive feedback always slows down the relaxation kinetics while negative feedback always speeds it up. Numerical simulations demonstrate that this relation provides a possible method to infer the feedback topology of autoregulatory gene networks by using time-series data of gene expression.

Spontaneous and posed facial expression in Parkinson's disease.

PubMed

Smith, M C; Smith, M K; Ellgring, H

1996-09-01

Spontaneous and posed emotional facial expressions in individuals with Parkinson's disease (PD, n = 12) were compared with those of healthy age-matched controls (n = 12). The intensity and amount of facial expression in PD patients were expected to be reduced for spontaneous but not posed expressions. Emotional stimuli were video clips selected from films, 2-5 min in duration, designed to elicit feelings of happiness, sadness, fear, disgust, or anger. Facial movements were coded using Ekman and Friesen's (1978) Facial Action Coding System (FACS). In addition, participants rated their emotional experience on 9-point Likert scales. The PD group showed significantly less overall facial reactivity than did controls when viewing the films. The predicted Group X Condition (spontaneous vs. posed) interaction effect on smile intensity was found when PD participants with more severe disease were compared with those with milder disease and with controls. In contrast, ratings of emotional experience were similar for both groups. Depression was positively associated with emotion rating but not with measures of facial activity. Spontaneous facial expression appears to be selectively affected in PD, whereas posed expression and emotional experience remain relatively intact.

Fascin and EMMPRIN expression in primary mucinous tumors of ovary: a tissue microarray study.

PubMed

Alici, Omer; Kefeli, Mehmet; Yildiz, Levent; Baris, Sancar; Karagoz, Filiz; Kandemir, Bedri

2014-12-01

The aim of this study was to compare the expressions of fascin and EMMPRIN in primary malignant, borderline and benign mucinous ovarian tumors, and to investigate the relationship of these markers with tumor progression and their applicability to differential diagnosis. An immunohistochemical study was performed for fascin and EMMPRIN using the tissue microarray technique. Eighty-one cases were included in the study; there were 37 benign, 25 borderline and 19 malignant primary mucinous ovarian tumors. For each case, a total staining score was determined, consisting of scores for extent of staining and intensity of staining. The cases were allocated to negative, weakly positive and strongly positive staining categories, according to the total staining score. Both of the markers were significantly negative in benign tumors as compared with borderline and malignant tumors. There was no significant difference between borderline and malignant groups for both markers. Sixty-eight percent of malignant tumors were stained positive by fascin, while this rate was 40% for borderline mucinous tumors. All malignant tumors were strongly stained positive for EMMPRIN, while this rate was 92% for borderline mucinous tumors. The rest of the cases stained weakly positive. No significant difference in staining score was found between fascin and EMMPRIN expression. In ovarian primary mucinous tumors, fascin and EMMPRIN may play an important role in tumor progression from benign tumor to carcinoma. In that context, EMMPRIN and fascin expression may have potential application in the differential diagnosis of some diagnostically problematic mucinous ovarian tumors. However, the differential diagnostic applicability of EMMPRIN appears to be more limited than that of fascin due to its wide spectrum of staining in mucinous ovarian tumors. Copyright © 2014 Elsevier GmbH. All rights reserved.

Relationships between maternal emotional expressiveness and children's sensitivity to teacher criticism.

PubMed

Mizokawa, Ai

2013-01-01

Caregivers' emotional responses to children influence children's social and emotional development. This study investigated the association between maternal emotional expressiveness in the context of mother-child interactions and young children's sensitivity to teacher criticism. Sensitivity to teacher criticism was assessed among 53 Japanese preschoolers using hypothetical scenarios in which a puppet child representing the participant made a small error, and a puppet teacher pointed out the error. Self-report questionnaires were used to measure maternal expressiveness. The results demonstrated that negative maternal expressiveness toward one's own children was positively related to children's ratings of their own ability and negatively related to children's motivation to continue with the task after teacher criticism. Positive maternal expressiveness was not related to children's sensitivity to criticism. These findings suggest that children who have experienced more negative emotion from mothers may be more likely to hold negative beliefs about how others will respond to their behavior more generally. This may, in turn, lead to a defensively positive view of one's own abilities and a disinclination to persevere as protection from additional opportunities for teacher evaluation.

Expression of microphthalmia transcription factor, S100 protein, and HMB-45 in malignant melanoma and pigmented nevi.

PubMed

Xia, Jianxin; Wang, Yanlong; Li, Fuqiu; Wang, Jinfeng; Mu, Yan; Mei, Xianglin; Li, Xue; Zhu, Wenjing; Jin, Xianhua; Yu, Kai

2016-09-01

Malignant melanoma (MM) is a type of malignant tumor, which originates from neural crest melanocytes. MM progresses rapidly and results in a high mortality rate. The present study aims to investigate the expression of microphthalmia transcription factor (MITF), the S100 protein, and HMB-45 in MM and pigmented nevi. A total of 32 MM samples (including three skin metastasis, three lymph node metastasis and two spindle cell MM samples), two Spitz nevus samples, four pigmented nevus samples and two blue nevus samples were collected. The expression levels of S100 protein, HMB-45, and MITF were observed via immunostaining. The S100 protein exhibited high positive rates in MM and pigment disorders (96.7 and 100%, respectively), but with low specificity. The S100 protein was also expressed in fibroblasts, myoepithelial cells, histocytes and Langerhans cells in normal skin samples. HMB-45 had high specificity. Its positive expression was only confined to MM cells and junctional nevus cells. Furthermore, HMB-45 was not expressed in melanocytes in the normal tissue samples around the tumor or in the benign intradermal nevus cells. MITF exhibited high specificity and high sensitivity. It was expressed in the nuclei of melanocytes, MM cells and nevus cells. It was observed to be strongly expressed in metastatic MM and spindle cell MMs. Thus, MITF may present as a specific immunomarker for the diagnosis and differential diagnosis of MM.

Grin and bear it: the influence of manipulated facial expression on the stress response.

PubMed

Kraft, Tara L; Pressman, Sarah D

2012-01-01

In the study reported here, we investigated whether covertly manipulating positive facial expressions would influence cardiovascular and affective responses to stress. Participants (N = 170) naive to the purpose of the study completed two different stressful tasks while holding chopsticks in their mouths in a manner that produced a Duchenne smile, a standard smile, or a neutral expression. Awareness was manipulated by explicitly asking half of all participants in the smiling groups to smile (and giving the other half no instructions related to smiling). Findings revealed that all smiling participants, regardless of whether they were aware of smiling, had lower heart rates during stress recovery than the neutral group did, with a slight advantage for those with Duchenne smiles. Participants in the smiling groups who were not explicitly asked to smile reported less of a decrease in positive affect during a stressful task than did the neutral group. These findings show that there are both physiological and psychological benefits from maintaining positive facial expressions during stress.

Aspects of the structure of film expression and anthropological paradigm of films reception in Croatian cinema and TV distribution.

PubMed

Svilicić, Niksa

2012-09-01

This research paper deals with one part of a comprehensive study called "Causality of narratological-semiotic aspects of the structure of film expression and paradigms of reception of Croatian feature film". It is conceived as a response to the hypothesis that the expression of narrative-semiotic terms correlate with the reception of the Croatian feature film audience and all them leads into a broader holistic i.e. anthropological context.The basic idea of scientific research is to analyze the complete feature productions since Croatian independence 1991 to date, presented at the National Film Festival (film festival in Pula), identify, define and isolate positive social narrative-semiotic stereotypes, which can then serve as a paradigm of better ratings and increase of the currently very low rating of domestic films in Croatian cinemas, as well as TV distribution. In other words, the paper will be analyzed and processed by a range of different effects based on narrative-semiotic, set design and mise-en-scène motives, used in the Croatian feature films since independence to date, that we assume to positively influence the mood of the viewer, and thus increase the rating of the film.

Protein expression patterns of cell cycle regulators in operable breast cancer.

PubMed

Zagouri, Flora; Kotoula, Vassiliki; Kouvatseas, George; Sotiropoulou, Maria; Koletsa, Triantafyllia; Gavressea, Theofani; Valavanis, Christos; Trihia, Helen; Bobos, Mattheos; Lazaridis, Georgios; Koutras, Angelos; Pentheroudakis, George; Skarlos, Pantelis; Bafaloukos, Dimitrios; Arnogiannaki, Niki; Chrisafi, Sofia; Christodoulou, Christos; Papakostas, Pavlos; Aravantinos, Gerasimos; Kosmidis, Paris; Karanikiotis, Charisios; Zografos, George; Papadimitriou, Christos; Fountzilas, George

2017-01-01

To evaluate the prognostic role of elaborate molecular clusters encompassing cyclin D1, cyclin E1, p21, p27 and p53 in the context of various breast cancer subtypes. Cyclin E1, cyclin D1, p53, p21 and p27 were evaluated with immunohistochemistry in 1077 formalin-fixed paraffin-embedded tissues from breast cancer patients who had been treated within clinical trials. Jaccard distances were computed for the markers and the resulted matrix was used for conducting unsupervised hierarchical clustering, in order to identify distinct groups correlating with prognosis. Luminal B and triple-negative (TNBC) tumors presented with the highest and lowest levels of cyclin D1 expression, respectively. By contrast, TNBC frequently expressed Cyclin E1, whereas ER-positive tumors did not. Absence of Cyclin D1 predicted for worse OS, while absence of Cyclin E1 for poorer DFS. The expression patterns of all examined proteins yielded 3 distinct clusters; (1) Cyclin D1 and/or E1 positive with moderate p21 expression; (2) Cyclin D1 and/or E1, and p27 positive, p53 protein negative; and, (3) Cyclin D1 or E1 positive, p53 positive, p21 and p27 negative or moderately positive. The 5-year DFS rates for clusters 1, 2 and 3 were 70.0%, 79.1%, 67.4% and OS 88.4%, 90.4%, 78.9%, respectively. It seems that the expression of cell cycle regulators in the absence of p53 protein is associated with favorable prognosis in operable breast cancer.

[The different experession of human papilloma viral types 6 and 11 in Uyghur and Chinese juvenile recurrent respiratory papillomatosis in a large pediatric population in Xinjiang].

PubMed

Zainura, Amrulla; Yalkun, Yasin; Wu, Mei

2013-11-01

To investigate the Human papilloma viral types 6 and 11 in a large pediatric population in XinJiang and the different expression in chinese and uyghur pediatric population. Using polymerase chain reaction (PCR), we analyzed paraffin embedded tissue in 42 cases of juvenile Recurrent Respiratory Papillomatosis (JRRP)and determined the HPV types 6 and 11, and to correlate these results with retrospectively analysis about those cases who were consecutively treated in our ENT department, meanwhile we carry out a critical review of the literature of JRRP. A total HPV infection positive rate was 97.61% (41/42), and HPV11 positive rate was 63.41% (41/26), HPV6 positive rate was 36.58% (41/15). In uyghur patient HPV11 positive rate was 65.38% (17/26), HPV6 positive rate was53. 33% (8/15). in Chince patient HPV11 positive rate was 34.61% (9/26), HPV6 positive rate was 46.67% (7/15). Juvenile laryngeal papilloma is associated with HPV11, HPV6 infection and we considered that HPV11 infection may be the important guideline of the evaluation of disease prognosis. but no statistical signtificance was determined in the patients of various ethnic groups in Xin jiang (P > 0.05).

Bodily Reactions to Emotional Words Referring to Own versus Other People's Emotions.

PubMed

Weis, Patrick P; Herbert, Cornelia

2017-01-01

According to embodiment theories, language and emotion affect each other. In line with this, several previous studies investigated changes in bodily responses including facial expressions, heart rate or skin conductance during affective evaluation of emotional words and sentences. This study investigates the embodiment of emotional word processing from a social perspective by experimentally manipulating the emotional valence of a word and its personal reference. Stimuli consisted of pronoun-noun pairs, i.e., positive, negative, and neutral nouns paired with possessive pronouns of the first or the third person ("my," "his") or the non-referential negation term ("no") as controls. Participants had to quickly evaluate the word pairs by key presses as either positive, negative, or neutral, depending on the subjective feelings they elicit. Hereafter, they elaborated the intensity of the feeling on a non-verbal scale from 1 (very unpleasant) to 9 (very pleasant). Facial expressions ( M. Zygomaticus , M. Corrugator ), heart rate, and, for exploratory purposes, skin conductance were recorded continuously during the spontaneous and elaborate evaluation tasks. Positive pronoun-noun phrases were responded to the quickest and judged more often as positive when they were self-related, i.e., related to the reader's self (e.g., "my happiness," "my joy") than when related to the self of a virtual other (e.g., "his happiness," "his joy"), suggesting a self-positivity bias in the emotional evaluation of word stimuli. Physiologically, evaluation of emotional, unlike neutral pronoun-noun pairs initially elicited an increase in mean heart rate irrespective of stimulus reference. Changes in facial muscle activity, M. Zygomaticus in particular, were most pronounced during spontaneous evaluation of positive other-related pronoun-noun phrases in line with theoretical assumptions that facial expressions are socially embedded even in situation where no real communication partner is present. Taken together, the present results confirm and extend the embodiment hypothesis of language by showing that bodily signals can be differently pronounced during emotional evaluation of self- and other-related emotional words.

Comparative study of ROR2 and WNT5a expression in squamous/adenosquamous carcinoma and adenocarcinoma of the gallbladder

PubMed Central

Wu, Zheng-Chun; Xiong, Li; Wang, Ling-Xiang; Miao, Xiong-Ying; Liu, Zi-Ru; Li, Dai-Qiang; Zou, Qiong; Liu, Kui-Jie; Zhao, Hua; Yang, Zhu-Lin

2017-01-01

AIM To investigate the expression and clinical pathological significance of ROR2 and WNT5a in gallbladder squamous/adenosquamous carcinoma (SC/ASC) and adenocarcinoma (AC). METHODS EnVision immunohistochemistry was used to stain for ROR2 and WNT5a in 46 SC/ASC patients and 80 AC patients. RESULTS Poorly differentiated AC among AC patients aged > 45 years were significantly more frequent compared with SC/ASC patients, while tumors with a maximal diameter > 3 cm in the SC/ASC group were significantly more frequent compared with the AC group. Positive ROR2 and WNT5a expression was significantly lower in SC/ASC or AC with a maximal mass diameter ≤ 3 cm, a TNM stage of I + II, no lymph node metastasis, no surrounding invasion, and radical resection than in patients with a maximal mass diameter > 3 cm, TNM stage IV, lymph node metastasis, surrounding invasion, and no resection. Positive ROR2 expression in patients with highly differentiated SC/ASC was significantly lower than in patients with poorly differentiated SC/ASC. Positive ROR2 and WNT5a expression levels in highly differentiated AC were significantly lower than in poorly differentiated AC. Kaplan-Meier survival analysis showed that differentiation degree, maximal mass diameter, TNM stage, lymph node metastasis, surrounding invasion, surgical procedure and the ROR2 and WNT5a expression levels were closely related to average survival of SC/ASC or AC. The survival of SC/ASC or AC patients with positive expression of ROR2 and WNT5a was significantly shorter than that of patients with negative expression results. Cox multivariate analysis revealed that poor differentiation, a maximal diameter of the mass ≥ 3 cm, TNM stage III or IV, lymph node metastasis, surrounding invasion, unresected surgery and positive ROR2 or WNT5a expression in the SC/ASC or AC patients were negatively correlated with the postoperative survival rate and positively correlated with mortality, which are risk factors and independent prognostic predictors. CONCLUSION SC/ASC or AC patients with positive ROR2 or WNT5a expression generally have a poor prognosis. PMID:28465645

Self-reflection and positive schizotypy in the adolescent brain.

PubMed

Debbané, Martin; Vrtička, Pascal; Lazouret, Marine; Badoud, Deborah; Sander, David; Eliez, Stephan

2014-01-01

Clinical and phenomenological accounts of schizophrenia suggest that impairments in self-reflective processes significantly contribute to psychopathological expression. Recent imaging studies observe atypical cerebral activation patterns during self-reflection, especially around the cortical midline structures, both in psychosis-prone adults and individuals with schizophrenia. Given that self-reflection processes consolidate during adolescence, and that early transient expression of psychosis (positive schizotypy) also arises during this period, the present study sought to examine whether atypical cerebral activation during self-reflection task could be associated with early schizotypic expression during adolescence. Forty-two neurotypical adolescent participants (19 females) aged from 12 to 19 (15.92±1.9) underwent a self-reflection task using functional neuroimaging (fMRI), where they had to evaluate trait adjectives (1 to 4 ratings) about themselves or their same sex best friend. The Schizotypal Personality Questionnaire (SPQ) was employed to assess positive schizotypic expression. Results showed that positive schizotypy in adolescents significantly correlated with cortical midline activation patterns in the dorsomedial prefrontal cortex (dmPFC) and the posterior cingulate cortex (PCC), as well as the dorsolateral PFC and the lingual gyrus. The results are consistent with previous imaging literature on self-reflection and schizophrenia. They further highlight that the relationship between self-reflection processes and positive schizotypy operates at the trait level of expression and can be observed as early as adolescence. Copyright © 2013 Elsevier B.V. All rights reserved.

High expression of Parkin predicts easier recurrence of patients with adjuvant transarterial chemoembolization.

PubMed

Zhang, Changlie; Song, Zhihong; Yu, Guangji

2017-10-01

To investigate the clinical significance of E3 ubiquitin ligase Parkin in patients with adjuvant transarterial chemoembolization after curative resection of hepatocellular carcinoma. Parkin expression of hepatocellular carcinomas was detected and its correlation with clinicopathological factors was analyzed with χ 2 test. The significance of Parkin in prognosis and recurrence was analyzed with log-rank test and the Cox-regression model. High expression of Parkin could result in lower recurrence-free survival rate instead of overall survival rate. Larger tumor size, positive tumor recurrence, advanced T, N, M and TNM stage were significantly associated with poorer prognosis. Larger tumor size, advanced T and TNM stage could lead to higher recurrence. High Parkin expression could predict easier recurrence to patients with adjuvant transarterial chemoembolization.

[The expression and clinical significance of EphA2 and E-cadherin in papillary thyroid carcinoma].

PubMed

Liu, Yan; Miao, Yuhua; Li, Xiaoming

2015-06-01

To investigate the expression and clinical significance of EphA2 and E cadherin proteins in papillary thyroid carcinoma tissues, and to explore the relationship between them. Using immunohistochemical SP/PV method, we detected the expression of EphA2 and E cadherin in tumors of 43 papillary thyroid carcinomas, 11 thyroid adenoma and 10 normal thyroid tissues, then studied their relationships with clinic pathological factors. The total positive rates of EphA2 and E cadherin expression were 58. 14% and 32. 56% in papillary thyroid carcinoma tissues, 18. 18% and 81. 81% in thyroid adenoma.tissues and they were 10. 00% and 100. 00% in normal thyroid tissues respectively. The positive expression of EphA2 in carcinoma tissues was higher than in the thyroid adenoma tissues and normal thyroid tissues (P<0. 05) and the positive expression of E cadherin in carcinoma tissues was lower than that in the thyroid adenoma tissues and normal thyroid tissues (P<0. 05). The positive expression of EphA2 and E cadherin was associated with lymph node metastasis and histological grade (P<0. 05), but it was not associated with all the clinic-pathological factors including age, sex and the tumor size (P>0. 05). In papillary thyroid carcinoma tissues, the expression of EphA2 was negatively correlated with the expression of E cadherin protein (r= -0. 416, P<0. 01). EphA2 and E cadherin may be involved in carcinogenesis and development of papillary thyroid carcinoma.

HLA-G expression in gastric carcinoma: clinicopathological correlations and prognostic impact.

PubMed

Murdaca, Giuseppe; Calamaro, Paola; Lantieri, Francesca; Pigozzi, Simona; Mastracci, Luca; Grillo, Federica; Magnani, Ottavia; Ceppa, Paola; Puppo, Francesco; Fiocca, Roberto

2018-05-29

To analyze expression of human leukocyte antigen-G (HLA-G) in gastric adenocarcinoma and correlate its expression with histological and clinical variables. A continuous series of 94 unselected patients with gastric adenocarcinoma (stage I to III) were selected. All histological and clinical variables were collected including the intensity of intra- and peri-tumor lymphocytic infiltration. HLA-G expression was investigated using immunohistochemistry. All histological samples analyzed for HLA-G expression were taken from the primary gastric lesion and included non-neoplastic mucosa. Evaluation of HLA-G expression was performed on the transition zone between tumor and non-neoplastic mucosa, and the invasive front of the tumor and assessment was performed as follows: percentage of positive (strong expression vs weak) cells. A variable amount of HLA-G-positive tumor cells was found in 24 out of 94 cases (25.5%). No significant correlation was found between HLA-G expression and other clinicopathological variables (sex, age, stage, grade, histotype). The overall median survival was worse in patients with HLA-G-positive adenocarcinoma (24.3 months, CI 95% 7.7-41.0) compared to those with HLA-G-negative tumors (66.3 months, CI 95% 53.0-79.7; p < 0.0001). Two- and 5-year survival rates of HLA-G-negative patients were 88 and 44%, respectively, while were 42 and 11% in those HLA-G-positive. This trend was observed in all stages but was more marked in stage III. HLA-G expression is associated with poor survival in stage III gastric cancer patients and represents a possible immunoescape mechanism of cancer cells.

A single sample study of dissociation between expressed and experienced pleasure by gender in mild depression.

PubMed

Brown, S L

Thirty male and thirty female adult subjects were divided equally into three groups on the basis of the Zung Self-Rating Depression Scale; mildly depressed (50-63), normal (40-49), and "low normal" (20-39). Observer ratings of positive affect were made during a one and one-half hour laboratory experiment, and self-ratings of pleasurable experience were collected at the end of the experiment. Results showed no significant differences between groups for self-report of experienced pleasure. However, a significant difference between groups was found for observer ratings of positive affect, with the mildly depressed and "low normal" subjects showing a shorter duration and a lower degree of positive affect than the normals. These results partially replicate and extended previous work. Implications for theory, research, and psychotherapy are discussed.

[CD69 expression on T cell surface in patients with obstructive sleep apnea hypopnea syndrome].

PubMed

Chen, Y H; Wang, P F; Wang, H J; Hu, X; Li, Z Y; Xiong, H Q

2017-02-20

Objective: To investigate the detection and significance of T cell CD69 expression in peripheral blood of patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Method: According to AHI, 81 OSAHS patients diagnosed by PSG were divided into 3 groups: light, medium and heavy, with 27 cases in each group; 27 patients without OSAHS as control group. Flow cytometry was used to detect the expression rate of CD69 in T cells, to analyze the correlation between the expression rate of CD69 on T cells and the gender, age, BMI, and PSG index. Result: ①The CD69 expression rate of T cells in peripheral blood of OSAHS patients with snoring degree increases gradually ( P < 0.05); Comparison between the two shows that there was no significant difference in CD69 expression rate on T cells between the control group and the mild group ( t = 1.649, P > 0.05); there were significant differences between the other groups ( P < 0.05). ②The CD69 expression rate of T cells in peripheral blood of OSAHS patients has no correlation with BMI, age and gender ( P > 0.05), were positively correlated with AHI, negatively correlated with LSaO₂ ( P < 0.01). ③The CD69 expression rate of T cells and AHI in 27 cases of severe OSAHS patients with a comprehensive treatment has significantly reduced, LSaO₂ increased significantly ( P < 0.01). Conclusion: Increased expression of CD69 in peripheral blood T cells may be one of the mechanisms of OSAHS complicated with cardiovascular disease. Detection of CD69 expression rate in T cells for reflecting the degree of disease in patients with OSAHS, assessment of risk of cardiovascular damage, have certain clinical significance. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

Do Dynamic Compared to Static Facial Expressions of Happiness and Anger Reveal Enhanced Facial Mimicry?

PubMed Central

Rymarczyk, Krystyna; Żurawski, Łukasz; Jankowiak-Siuda, Kamila; Szatkowska, Iwona

2016-01-01

Facial mimicry is the spontaneous response to others’ facial expressions by mirroring or matching the interaction partner. Recent evidence suggested that mimicry may not be only an automatic reaction but could be dependent on many factors, including social context, type of task in which the participant is engaged, or stimulus properties (dynamic vs static presentation). In the present study, we investigated the impact of dynamic facial expression and sex differences on facial mimicry and judgment of emotional intensity. Electromyography recordings were recorded from the corrugator supercilii, zygomaticus major, and orbicularis oculi muscles during passive observation of static and dynamic images of happiness and anger. The ratings of the emotional intensity of facial expressions were also analysed. As predicted, dynamic expressions were rated as more intense than static ones. Compared to static images, dynamic displays of happiness also evoked stronger activity in the zygomaticus major and orbicularis oculi, suggesting that subjects experienced positive emotion. No muscles showed mimicry activity in response to angry faces. Moreover, we found that women exhibited greater zygomaticus major muscle activity in response to dynamic happiness stimuli than static stimuli. Our data support the hypothesis that people mimic positive emotions and confirm the importance of dynamic stimuli in some emotional processing. PMID:27390867

Expression of gap junction genes connexin 32 and connexin 43 mRNAs and proteins, and their role in hepatocarcinogenesis

PubMed Central

Ma, Xiang-Dong; Ma, Xing; Sui, Yan-Fang; Wang, Wen-Liang

2002-01-01

AIM: To investigate the relationship between hepatocarcinogenesis and the expression of connexin32 (cx32), connexin43 (cx43) mRNAs and proteins in vitro. METHODS: Gap junction genes cx32 and cx43 mRNA in hepatocellular carcinoma cell lines HHCC, SMMC-7721 and normal liver cell line QZG were detected by in situ hybridization (ISH) with digoxin-labeled cx32, and cx43 cDNA probes. Expression of Cx32 and Cx43 proteins in the cell lines was revealed by indirect immuno-fluorescence and flow cytometry (FCM). RESULTS: Blue positive hybridization signals of cx32 and cx43 mRNAs detected by ISH with cx32 and cx43 cDNA probes respectively were located in cytoplasm of cells of HHCC, SMMC-7721 and QZG. No significant difference of either cx32 mRNA or cx43 mRNA was tested among HHCC, SMMC-7721 and QZG (P = 2.673, HHCC vs QZG; P = 1.375, SMMC-7721 vs QZG). FCM assay showed that the positive rates of Cx32 protein in HHCC, SMMC-7721 and QZG were 0.7%, 1.7% and 99.0%, and the positive rates of Cx43 protein in HHCC, SMMC-7721 and QZG were 7.3%, 26.5% and 99.1% respectively. Significant differences of both Cx32 and Cx43 protein expression existed between hepatocellular carcinoma cell lines and normal liver cell line (P = 0.0069, HHCC vs QZG; P = 0.0087, SMMC-7721 vs QZG). Moreover, the fluorescent intensities of Cx32 and Cx43 proteins in HHCC, SMMC-7721 were lower than that in QZG. CONCLUSION: Hepatocellular carcinoma cell lines HHCC and SMMC-7721 exhibited lower positive rates and fluorescent intensities of Cx32, Cx43 proteins compared with that of normal liver cell line QZG. It is suggested that lower expression of both Cx32 and Cx43 proteins in hepatocellular carcinoma cells could play pivotal roles in the hepatocarcinogenesis. Besides, genetic defects of cx32 and cx43 in post-translational processing should be considered. PMID:11833073

EGFR Mutations and ALK Rearrangements Are Associated with Low Response Rates to PD-1 Pathway Blockade in Non-Small Cell Lung Cancer: A Retrospective Analysis.

PubMed

Gainor, Justin F; Shaw, Alice T; Sequist, Lecia V; Fu, Xiujun; Azzoli, Christopher G; Piotrowska, Zofia; Huynh, Tiffany G; Zhao, Ling; Fulton, Linnea; Schultz, Katherine R; Howe, Emily; Farago, Anna F; Sullivan, Ryan J; Stone, James R; Digumarthy, Subba; Moran, Teresa; Hata, Aaron N; Yagi, Yukako; Yeap, Beow Y; Engelman, Jeffrey A; Mino-Kenudson, Mari

2016-09-15

PD-1 inhibitors are established agents in the management of non-small cell lung cancer (NSCLC); however, only a subset of patients derives clinical benefit. To determine the activity of PD-1/PD-L1 inhibitors within clinically relevant molecular subgroups, we retrospectively evaluated response patterns among EGFR-mutant, anaplastic lymphoma kinase (ALK)-positive, and EGFR wild-type/ALK-negative patients. We identified 58 patients treated with PD-1/PD-L1 inhibitors. Objective response rates (ORR) were assessed using RECIST v1.1. PD-L1 expression and CD8(+) tumor-infiltrating lymphocytes (TIL) were evaluated by IHC. Objective responses were observed in 1 of 28 (3.6%) EGFR-mutant or ALK-positive patients versus 7 of 30 (23.3%) EGFR wild-type and ALK-negative/unknown patients (P = 0.053). The ORR among never- or light- (≤10 pack years) smokers was 4.2% versus 20.6% among heavy smokers (P = 0.123). In an independent cohort of advanced EGFR-mutant (N = 68) and ALK-positive (N = 27) patients, PD-L1 expression was observed in 24%/16%/11% and 63%/47%/26% of pre-tyrosine kinase inhibitor (TKI) biopsies using cutoffs of ≥1%, ≥5%, and ≥50% tumor cell staining, respectively. Among EGFR-mutant patients with paired, pre- and post-TKI-resistant biopsies (N = 57), PD-L1 expression levels changed after resistance in 16 (28%) patients. Concurrent PD-L1 expression (≥5%) and high levels of CD8(+) TILs (grade ≥2) were observed in only 1 pretreatment (2.1%) and 5 resistant (11.6%) EGFR-mutant specimens and was not observed in any ALK-positive, pre- or post-TKI specimens. NSCLCs harboring EGFR mutations or ALK rearrangements are associated with low ORRs to PD-1/PD-L1 inhibitors. Low rates of concurrent PD-L1 expression and CD8(+) TILs within the tumor microenvironment may underlie these clinical observations. Clin Cancer Res; 22(18); 4585-93. ©2016 AACRSee related commentary by Gettinger and Politi, p. 4539. ©2016 American Association for Cancer Research.

Overexpression of neuromedin U is correlated with regional metastasis of head and neck squamous cell carcinoma

PubMed Central

Wang, Lei; Chen, Chen; Li, Fen; Hua, Qing-Quan; Chen, Shiming; Xiao, Bokui; Dai, Mengyuan; Li, Man; Zheng, Anyuan; Yu, Di; Hu, Zhang Wei; Tao, Zezhang

2016-01-01

Regional metastasis is an important prognostic factor for patients with head and neck squamous cell carcinoma (HNSCC). Neuromedin U (Nmu) is a secreted neuropeptide, named due to its potent uterine contraction-inducing activity. The aim of the present study was to analyze the significance of Nmu in the regional metastasis of HNSCC. The characteristics of 240 patients recruited from the Department of Otolaryngology Head and Neck Surgery, Renmin Hospital of Wuhan University (Wuhan, China) were summarized retrospectively. The positive rate of neck dissection was analyzed according to the material. The expression levels of Nmu in human tumor samples were analyzed using immunohistochemistry. Subsequently, the expression of Nmu was investigated using a tissue microassay to analyze the association between Nmu protein expression and Tumor Node Metastasis (TNM) status. The positive rate of neck dissection was 51.4% in the study sample. The expression levels of Nmu in primary tumors with regional metastasis were higher, compared with those without metastasis. There was increased protein expression of Nmu in the advanced tumor tissues. The data obtained in the present study demonstrated that the expression of Nmu was correlated with regional metastasis and TNM status. Overexpression of Nmu may be involved in the process of regional metastasis of HNSCC, and may serve as a novel and valuable biomarker for predicting regional metastasis in patients with HNSCC. PMID:27279246

Identifying Epigenetic Biomarkers using Maximal Relevance and Minimal Redundancy Based Feature Selection for Multi-Omics Data.

PubMed

Mallik, Saurav; Bhadra, Tapas; Maulik, Ujjwal

2017-01-01

Epigenetic Biomarker discovery is an important task in bioinformatics. In this article, we develop a new framework of identifying statistically significant epigenetic biomarkers using maximal-relevance and minimal-redundancy criterion based feature (gene) selection for multi-omics dataset. Firstly, we determine the genes that have both expression as well as methylation values, and follow normal distribution. Similarly, we identify the genes which consist of both expression and methylation values, but do not follow normal distribution. For each case, we utilize a gene-selection method that provides maximal-relevant, but variable-weighted minimum-redundant genes as top ranked genes. For statistical validation, we apply t-test on both the expression and methylation data consisting of only the normally distributed top ranked genes to determine how many of them are both differentially expressed andmethylated. Similarly, we utilize Limma package for performing non-parametric Empirical Bayes test on both expression and methylation data comprising only the non-normally distributed top ranked genes to identify how many of them are both differentially expressed and methylated. We finally report the top-ranking significant gene-markerswith biological validation. Moreover, our framework improves positive predictive rate and reduces false positive rate in marker identification. In addition, we provide a comparative analysis of our gene-selection method as well as othermethods based on classificationperformances obtained using several well-known classifiers.

MicroRNA array normalization: an evaluation using a randomized dataset as the benchmark.

PubMed

Qin, Li-Xuan; Zhou, Qin

2014-01-01

MicroRNA arrays possess a number of unique data features that challenge the assumption key to many normalization methods. We assessed the performance of existing normalization methods using two microRNA array datasets derived from the same set of tumor samples: one dataset was generated using a blocked randomization design when assigning arrays to samples and hence was free of confounding array effects; the second dataset was generated without blocking or randomization and exhibited array effects. The randomized dataset was assessed for differential expression between two tumor groups and treated as the benchmark. The non-randomized dataset was assessed for differential expression after normalization and compared against the benchmark. Normalization improved the true positive rate significantly in the non-randomized data but still possessed a false discovery rate as high as 50%. Adding a batch adjustment step before normalization further reduced the number of false positive markers while maintaining a similar number of true positive markers, which resulted in a false discovery rate of 32% to 48%, depending on the specific normalization method. We concluded the paper with some insights on possible causes of false discoveries to shed light on how to improve normalization for microRNA arrays.

MicroRNA Array Normalization: An Evaluation Using a Randomized Dataset as the Benchmark

PubMed Central

Qin, Li-Xuan; Zhou, Qin

2014-01-01

MicroRNA arrays possess a number of unique data features that challenge the assumption key to many normalization methods. We assessed the performance of existing normalization methods using two microRNA array datasets derived from the same set of tumor samples: one dataset was generated using a blocked randomization design when assigning arrays to samples and hence was free of confounding array effects; the second dataset was generated without blocking or randomization and exhibited array effects. The randomized dataset was assessed for differential expression between two tumor groups and treated as the benchmark. The non-randomized dataset was assessed for differential expression after normalization and compared against the benchmark. Normalization improved the true positive rate significantly in the non-randomized data but still possessed a false discovery rate as high as 50%. Adding a batch adjustment step before normalization further reduced the number of false positive markers while maintaining a similar number of true positive markers, which resulted in a false discovery rate of 32% to 48%, depending on the specific normalization method. We concluded the paper with some insights on possible causes of false discoveries to shed light on how to improve normalization for microRNA arrays. PMID:24905456

[The expression of MMP-2 and MMP-9 in adenoid cystic carcinoma of lacrimal gland].

PubMed

Zhang, Lei; Zhang, Hong; Song, Guo-xiang; Lin, Ting-ting; Xu, Guang-chang; Zhu, Li-min

2013-01-01

To investigate the expression of matrix metal proteinase (MMP)-2 and MMP-9 in adenoid cystic carcinoma of lacrimal gland as well as their relation with biological behaviour of adenoid cystic carcinoma. Experimental study. The research objects were 60 cases of adenoid cystic carcinoma of lacrimal gland which were collected from No.2 Hospital of Tianjin Medical University from January 1991 to Jule 2011. There were 25 males and 35 females aged from 29 to 42 years. Based on histological revision, there were 36 cases of cribriform-tubular subtype and 24 cases of solid subtype. Forty-five cases were primary lesions and 15 cases were recurrent lesions. Ten samples of normal lacrimal gland around polymorphic adenoma were selected as the control group. The expression of CD105, MMP-2 and MMP-9 were evaluated by immunohistochemistry. The microvessel density (MVD) was defined by expression of CD105. One way ANOVA, χ(2)-test and spearman correlation test were used to analyzed the data. The number of MVD [(17.71 ± 5.63)/100 folds field of vision] and the positive rates of MMP-2 (45.0%, 27/60) and MMP-9 (55.0%, 33/60) in the samples of adenoid cystic carcinoma of lacrimal gland were higher than those in the normal lacrimal gland [the number of MVD was (0.70 ± 0.95)/100 folds field of vision, the expressions of MMP-2 and MMP-9 were negative] (t' = 2.039, P < 0.05; χ(2) = 5.550, P < 0.05; χ(2) = 8.315, P < 0.01), the solid subtypes had more MVD [(26.12 ± 5.32)/100 folds field of vision] and higher positive rates of MMP-2 (62.5%, 15/24) and MMP-9 (79.2%, 19/24) than the cribriform-tubular subtypes (t' = 2.060, P < 0.05; χ(2) = 4.950, P < 0.05; χ(2) = 9.439, P < 0.05); the recurrent lesions had more MVD and higher positive rate of MMP-2 and MMP-9 than the primary lesions (t' = 2.129, P < 0.05; χ(2) = 9.899, P < 0.05; χ(2) = 8.103, P < 0.05). The number of MVD in ACC of lacrimal gland patients was correlated with the positive rate of MMP-2 and MMP-9 respectively (rs = 0.636, P < 0.05; rs = 0.524, P < 0.05). The number of MVD and the expression of MMP-2 and MMP-9 are higher level in adenoid cystic carcinoma of lacrimal gland and are significantly correlated with pathological type and recurrence. Detecting the number of MVD and the expression of MMP-2 and MMP-9 may become biological indexes for malignancy, recurrence and metastasis of adenoid cystic carcinoma of lacrimal gland.

Novel stimuli are negative stimuli: evidence that negative affect is reduced in the mere exposure effect.

PubMed

Robinson, Brent M; Elias, Lorin J

2005-04-01

Repeated exposure of a nonreinforced stimulus results in an increased preference for that stimulus, the mere exposure effect. The present study repeatedly presented positive, negative, and neutrally affective faces to 48 participants while they made judgments about the emotional expression. Participants then rated the likeability of novel neutrally expressive faces and some of these previously presented faces, this time in their neutral expression. Faces originally presented as happy were rated as the most likeable, followed by faces originally presented as neutral. Negative and novel faces were not rated significantly differently from each other. These findings support the notion that the increase in preference towards repeatedly presented stimuli is the result of the reduction in negative affect, consistent with the modified two-factor uncertainty-reduction model and classical conditioning model of the mere exposure effect.

The Expression and Significance of Feces Cyclooxygensae-2 mRNA in Colorectal Cancer and Colorectal Adenomas

PubMed Central

Li, Xiaofeng; Kong, Lixia; Liao, Suhuan; Lu, Jing; Ma, Lin; Long, Xiaohua

2017-01-01

Background/Aim: This study aims to explore the expression and significance of feces cyclooxygensae-2 (COX-2) mRNA in colorectal cancer and colorectal adenomas. Materials and Methods: The expression of feces COX-2 mRNA in colorectal cancer (n = 28), colorectal adenomas (n = 54), and normal control group (n = 11) were examined by reverse transcriptase polymerase chain reaction (RT-PCR). The positive rate of fecal occult blood test (FOBT) were detected in colorectal cancer (n = 30), colorectal adenomas (n = 56), and normal control group (n = 11); the sensitivity of the two methods was also compared. Results: The positive rate of feces COX-2 mRNA in colorectal cancer was 82.1% (25/28), which was significantly higher than colorectal adenomas 59.3% (32/54), and normal tissues 18.2% (2/11), the difference being significant between the three groups (χ2= 13.842, P = 0.001). The positive rate of FOBT in colorectal cancer was 73.3% (10/30), which was significantly higher than colorectal adenomas 10.7% (6/56) and normal tissues 9.1% (1/11), the difference being significant between these three groups (χ2= 7.525, P = 0.023). There was no significant association between feces COX-2 expression and various clinical pathological features of colorectal cancer and colorectal adenomas (P > 0.05). The sensitivity of the RT-PCR method is higher than FOBT, however, the specificity of FOBT is slightly higher than RT-PCR. Conclusions: High expression of feces COX-2 mRNA in colorectal adenomas and colorectal cancer is a common event; it is an early event in the development of colorectal adenomas to colorectal cancer. Feces COX-2 mRNA has a high sensitivity for detect colorectal cancer; combination with FOBT will be the best alternative. Feces COX-2 can be potentially used in the early diagnosis and screening of colorectal cancer. PMID:28139497

The expression and significance of feces cyclooxygensae-2 mRNA in colorectal cancer and colorectal adenomas.

PubMed

Li, Xiaofeng; Kong, Lixia; Liao, Suhuan; Lu, Jing; Ma, Lin; Long, Xiaohua

2017-01-01

This study aims to explore the expression and significance of feces cyclooxygensae-2 (COX-2) mRNA in colorectal cancer and colorectal adenomas. The expression of feces COX-2 mRNA in colorectal cancer (n = 28), colorectal adenomas (n = 54), and normal control group (n = 11) were examined by reverse transcriptase polymerase chain reaction (RT-PCR). The positive rate of fecal occult blood test (FOBT) were detected in colorectal cancer (n = 30), colorectal adenomas (n = 56), and normal control group (n = 11); the sensitivity of the two methods was also compared. The positive rate of feces COX-2 mRNA in colorectal cancer was 82.1% (25/28), which was significantly higher than colorectal adenomas 59.3% (32/54), and normal tissues 18.2% (2/11), the difference being significant between the three groups (χ2= 13.842,P= 0.001). The positive rate of FOBT in colorectal cancer was 73.3% (10/30), which was significantly higher than colorectal adenomas 10.7% (6/56) and normal tissues 9.1% (1/11), the difference being significant between these three groups (χ2= 7.525,P= 0.023). There was no significant association between feces COX-2 expression and various clinical pathological features of colorectal cancer and colorectal adenomas (P > 0.05). The sensitivity of the RT-PCR method is higher than FOBT, however, the specificity of FOBT is slightly higher than RT-PCR. High expression of feces COX-2 mRNA in colorectal adenomas and colorectal cancer is a common event; it is an early event in the development of colorectal adenomas to colorectal cancer. Feces COX-2 mRNA has a high sensitivity for detect colorectal cancer; combination with FOBT will be the best alternative. Feces COX-2 can be potentially used in the early diagnosis and screening of colorectal cancer.

Expression and significance of cyclooxygenase-2 mRNA in benign and malignant ascites

PubMed Central

Lu, Jing; Li, Xiao-Feng; Kong, Li-Xia; Ma, Lin; Liao, Su-Huan; Jiang, Chang-You

2013-01-01

AIM: To investigate the mRNA expression of cyclooxygensae-2 (COX-2) in benign and malignant ascites, and to explore the difference in COX-2 mRNA expression among different diseases. METHODS: A total of 36 samples were collected from the Fifth Affiliated Hospital of Sun Yat-Sen University and divided into two experimental groups: benign ascites (n = 21) and malignant ascites (n = 15). Benign ascites included cirrhotic ascites (n = 10) and tuberculous ascites (n = 5). Malignant ascites included oophoroma (n = 7), cancer of colon (n = 5), cancer of the liver (n = 6), gastric cancer (n = 2), and bladder carcinoma (n = 1). The mRNA expression of COX-2 in ascites was examined with reverse transcriptase polymerase chain reaction (RT-PCR) technology, and the positive rate of COX-2 mRNA was compared between different diseases. RESULTS: The positive rate of COX-2 mRNA in malignant ascites was 42.9% (9/21), which was significantly higher than in benign ascites, 6.7% (1/15), difference being significant between these two groups (χ2 = 4.051, P = 0.044). The proportion of the positive rate in the malignant ascites was as follows: ovarian cancers 57.1% (4/7), colon cancer 40.0% (2/5), liver cancer 33.3% (2/6), gastric cancer 50.0% (1/2), and bladder cancer 0.00% (0/1). However, there was no significant difference in COX-2 mRNA expression among various tumors with malignant ascites (χ2 = 1.614, P = 0.806). Among the benign ascites, COX-2 mRNA levels were different between the tuberculous ascites (0/5) and cirrhotic ascites (1/10), but there was no significant difference (P = 1.000). CONCLUSION: COX-2 mRNA, detected by RT-PCR, is useful in the differential diagnosis of benign and malignant ascites, which also has potential value in the clinical diagnosis of tumors. PMID:24187465

Emotional Expression and Heart Rate in High-Risk Infants during the Face-To-Face/Still-Face

PubMed Central

Mattson, Whitney I.; Ekas, Naomi V.; Lambert, Brittany; Tronick, Ed; Lester, Barry M.; Messinger, Daniel S.

2013-01-01

In infants, eye constriction—the Duchenne marker—and mouth opening appear to index the intensity of both positive and negative facial expressions. We combined eye constriction and mouth opening that co-occurred with smiles and cry-faces (respectively, the prototypic expressions of infant joy and distress) to measure emotional expression intensity. Expression intensity and heart rate were measured throughout the Face-to-Face/Still Face (FFSF) in a sample of infants with prenatal cocaine exposure who were at risk for developmental difficulties. Smiles declined and cry-faces increased in the still-face episode, but the distribution of eye constriction and mouth opening in smiles and cry-faces did not differ across episodes of the FFSF. As time elapsed in the still face episode potential indices of intensity increased, cry-faces were more likely to be accompanied by eye constriction and mouth opening. During cry-faces there were also moderately stable individual differences in the quantity of eye constriction and mouth opening. Infant heart rate was higher during cry-faces and lower during smiles, but did not vary with intensity of expression or by episode. In sum, infants express more intense negative affect as the still-face progresses, but do not show clear differences in expressive intensity between episodes of the FFSF. PMID:24095807

Acute changes in cellular zinc alters zinc uptake rates prior to zinc transporter gene expression in Jurkat cells.

PubMed

Holland, Tai C; Killilea, David W; Shenvi, Swapna V; King, Janet C

2015-12-01

A coordinated network of zinc transporters and binding proteins tightly regulate cellular zinc levels. Canonical responses to zinc availability are thought to be mediated by changes in gene expression of key zinc transporters. We investigated the temporal relationships of actual zinc uptake with patterns of gene expression in membrane-bound zinc transporters in the human immortalized T lymphocyte Jurkat cell line. Cellular zinc levels were elevated or reduced with exogenous zinc sulfate or N,N,N',N-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), respectively. Excess zinc resulted in a rapid 44 % decrease in the rate of zinc uptake within 10 min. After 120 min, the expression of metallothionein (positive control) increased, as well as the zinc exporter, ZnT1; however, the expression of zinc importers did not change during this time period. Zinc chelation with TPEN resulted in a rapid twofold increase in the rate of zinc uptake within 10 min. After 120 min, the expression of ZnT1 decreased, while again the expression of zinc importers did not change. Overall, zinc transporter gene expression kinetics did not match actual changes in cellular zinc uptake with exogenous zinc or TPEN treatments. This suggests zinc transporter regulation may be the initial response to changes in zinc within Jurkat cells.

I know how you felt last night, or do I? Self- and external ratings of emotions in REM sleep dreams.

PubMed

Sikka, Pilleriin; Valli, Katja; Virta, Tiina; Revonsuo, Antti

2014-04-01

We investigated whether inconsistencies in previous studies regarding emotional experiences in dreams derive from whether dream emotions are self-rated or externally evaluated. Seventeen subjects were monitored with polysomnography in the sleep laboratory and awakened from every rapid eye movement (REM) sleep stage 5 min after the onset of the stage. Upon awakening, participants gave an oral dream report and rated their dream emotions using the modified Differential Emotions Scale, whereas external judges rated the participants' emotions expressed in the dream reports, using the same scale. The two approaches produced diverging results. Self-ratings, as compared to external ratings, resulted in greater estimates of (a) emotional dreams; (b) positively valenced dreams; (c) positive and negative emotions per dream; and (d) various discrete emotions represented in dreams. The results suggest that this is mostly due to the underrepresentation of positive emotions in dream reports. Possible reasons for this discrepancy are discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

PD-L1 expression in EBV-negative diffuse large B-cell lymphoma: clinicopathologic features and prognostic implications.

PubMed

Xing, Wei; Dresser, Karen; Zhang, Rui; Evens, Andrew M; Yu, Hongbo; Woda, Bruce A; Chen, Benjamin J

2016-09-13

Programmed cell death ligand 1 (PD-L1) is a cell surface glycoprotein that regulates the cellular immune response and serves as a targetable immune checkpoint molecule. PD-L1 is expressed on tumor cells and the immune microenvironment of several human malignancies, including a subset of aggressive lymphomas. We sought to investigate further the clinical and pathologic features of EBV-negative diffuse large B-cell lymphoma (DLBCL) cases that express PD-L1. Immunohistochemical staining using an anti-PD-L1 monoclonal antibody was performed on DLBCL cases from 86 patients. These patients received standard chemotherapy treatment and were followed for up to 175 months. Overall, 14 cases (16%) were considered positive for PD-L1 in tumor cells. In comparison with PD-L1 negative cases, PD-L1 positive cases had a higher rate of non-GCB type (71% vs. 30%, P=0.0060), and higher Ann Arbor stage (II-IV) (100% vs. 73%, P=0.0327). No significant differences were seen in the immunohistochemical expression of BCL2, MYC, or Ki67. Patients with tumors expressing PD-L1 demonstrated inferior overall survival (OS) upon long term follow up (P=0.0447). Both age/sex-adjusted and multivariate analyses identified PD-L1 as an independent predictor for OS (P=0.0101 and P=0.0424). There was no significant difference, however, in terms of remission rates after first treatment, relapse rates, and progression free survival between the groups. Identification of DLBCL cases that express PD-L1 may serve to select a subset of patients that could further benefit from targeted immunotherapy.

PD-L1 expression in EBV-negative diffuse large B-cell lymphoma: clinicopathologic features and prognostic implications

PubMed Central

Xing, Wei; Dresser, Karen; Zhang, Rui; Evens, Andrew M.; Yu, Hongbo; Woda, Bruce A.; Chen, Benjamin J.

2016-01-01

Programmed cell death ligand 1 (PD-L1) is a cell surface glycoprotein that regulates the cellular immune response and serves as a targetable immune checkpoint molecule. PD-L1 is expressed on tumor cells and the immune microenvironment of several human malignancies, including a subset of aggressive lymphomas. We sought to investigate further the clinical and pathologic features of EBV-negative diffuse large B-cell lymphoma (DLBCL) cases that express PD-L1. Immunohistochemical staining using an anti-PD-L1 monoclonal antibody was performed on DLBCL cases from 86 patients. These patients received standard chemotherapy treatment and were followed for up to 175 months. Overall, 14 cases (16%) were considered positive for PD-L1 in tumor cells. In comparison with PD-L1 negative cases, PD-L1 positive cases had a higher rate of non-GCB type (71% vs. 30%, P=0.0060), and higher Ann Arbor stage (II-IV) (100% vs. 73%, P=0.0327). No significant differences were seen in the immunohistochemical expression of BCL2, MYC, or Ki67. Patients with tumors expressing PD-L1 demonstrated inferior overall survival (OS) upon long term follow up (P=0.0447). Both age/sex-adjusted and multivariate analyses identified PD-L1 as an independent predictor for OS (P=0.0101 and P=0.0424). There was no significant difference, however, in terms of remission rates after first treatment, relapse rates, and progression free survival between the groups. Identification of DLBCL cases that express PD-L1 may serve to select a subset of patients that could further benefit from targeted immunotherapy. PMID:27527850

Clinical Significance of SASH1 Expression in Glioma.

PubMed

Yang, Liu; Zhang, Haitao; Yao, Qi; Yan, Yingying; Wu, Ronghua; Liu, Mei

2015-01-01

SAM and SH3 domain containing 1 (SASH1) is a recently discovered tumor suppressor gene. The role of SASH1 in glioma has not yet been described. We investigated SASH1 expression in glioma cases to determine its clinical significance on glioma pathogenesis and prognosis. We produced tissue microarrays using 121 patient-derived glioma samples and 30 patient-derived nontumor cerebral samples. Immunohistochemistry and Western blotting were used to evaluate SASH1 expression. We used Fisher's exact tests to determine relationships between SASH1 expression and clinicopathological characteristics; Cox regression analysis to evaluate the independency of different SASH1 expression; Kaplan-Meier analysis to determine any correlation of SASH1 expression with survival rate. SASH1 expression was closely correlated with the WHO glioma grade. Of the 121 cases, 66.9% with low SASH1 expression were mostly grade III-IV cases, whereas 33.1% with high SASH1 expression were mostly grades I-II. Kaplan-Meier analysis revealed a significant positive correlation between SASH1 expression and postoperative survival. SASH1 was widely expressed in normal and low-grade glioma tissues. SASH1 expression strongly correlated with glioma grades, showing higher expression at a lower grade, which decreased significantly as grade increased. Furthermore, SASH1 expression was positively correlated with better postoperative survival in patients with glioma.

Grb7 is over-expressed in cervical cancer and facilitate invasion and inhibit apoptosis in cervical cancer cells.

PubMed

Zhao, Hong-Bing; Zhang, Xi-Feng; Jia, Xue-Lin; Wang, Hao-Bin

2017-09-01

Growth factor receptor bound protein-7 (Grb7) is a multi-domain adaptor protein that is co-opted by numerous tyrosine kinases involved in various cellular signaling. The objective of this study was to investigate the expression of Grb7 and its clinicopathological significance in cervical cancer. Utilising immunohistochemical staining, we examined the expression of Grb7 in 120 cases of human cervical cancer tissue and 10 cases of adjacent non-cancerous cervical tissue. The positive rate of Grb7 protein expression was 34.2%, which was significantly higher than that in adjacent non-cancerous cervical tissue (0%, p<0.05). The expression of Grb7 was found to be correlated with age, tumor size, serosal invasion, differentiated degree, tumor stage, early or advanced stage and lymph node metastasis. Kaplan-Meier survival analysis showed that patients with positive Grb7 protein expression had a lower overall survival rate than patients without Grb7 expression. In addition, Grb7 plays an important role in promoting tumor progression, including invasion and anti-apoptosis, in cervical cancer cell line. Down-regulation of Grb7 repressed the expression of MMP-9 and Bcl-2, and increased the expression of Bax in Grb7 knockdown Hela cells. Cell invasion assay showed decreased number of Grb7 knockdown Hela cells (18.7±2.1) compared to Hela cells (65.3±2.5, P<0.05). Our results indicated that Grb7 over-expression may facilitate invasion and inhibit apoptosis in cervical cancer and Grb7 is a potentially molecular target of cervical cancer chemotherapy. Copyright © 2017 Elsevier GmbH. All rights reserved.

Epidermal growth factor receptor gene amplification in surgical resected Japanese lung cancer.

PubMed

Sasaki, Hidefumi; Shimizu, Shigeki; Okuda, Katsuhiro; Kawano, Osamu; Yukiue, Haruhiro; Yano, Motoki; Fujii, Yoshitaka

2009-06-01

To evaluate the epidermal growth factor receptor (EGFR) protein expression and increased copy number as predictors of clinical outcome in patients with non-small-cell lung cancer (NSCLC), we have performed fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). We investigated the EGFR increased copy number and EGFR protein expression statuses in 109 surgically treated NSCLC cases. The presence or absence of EGFR mutations of kinase domains was analyzed by genotyping analysis and sequences, and already reported. EGFR increased copy number was defined as Cappuzzo et al. criteria. FISH positive was found from 36/109 (33.0%) lung cancer patients, including 30 high polysomy cases and 6 gene amplification cases. FISH-positive cases were significantly correlated with worse prognosis (log-rank test p=0.0097). Within EGFR-mutant patients (n=55), FISH-positive cases were also correlated with poor prognosis (p=0.0255). FISH-negative tumors were found to be more frequently well-differentiated histology. Smoking status (never smoker vs. smoker, p=0.1510), and gender (p=0.5248) did not correlated with FISH positive. EGFR IHC results were correlated with FISH results (p=0.004), but not correlated with prognosis (p=0.2815). Although EGFR FISH-positive rate did not correlated with EGFR mutation (p=0.1973), EGFR polysomy or amplification cases were correlated with EGFR mutations (p=0.0023). In conclusion, the EGFR FISH-positive rate in Japanese patients with NSCLC was similar to rates in Western populations, unlike the higher frequencies of EGFR mutation in East Asians. A high EGFR gene copy number might have shorter survival in NSCLC.

The Molecular Detection and Clinical Significance of ALK Rearrangement in Selected Advanced Non-Small Cell Lung Cancer: ALK Expression Provides Insights into ALK Targeted Therapy

PubMed Central

Zhang, Ning-Ning; Liu, Yu-Tao; Ma, Li; Wang, Lin; Hao, Xue-Zhi; Yuan, Zheng; Lin, Dong-Mei; Li, Dan; Zhou, Yu-Jie; Lin, Hua; Han, Xiao-Hong; Sun, Yan; Shi, Yuankai

2014-01-01

Background This study aimed to elucidate clinical significance of anaplastic lymphoma kinase (ALK) rearrangement in selected advanced non-small cell lung cancer (NSCLC), to compare the application of different ALK detection methods, and especially evaluate a possible association between ALK expression and clinical outcomes in crizotinib-treated patients. Methods ALK status was assessed by fluorescent in situ hybridization (FISH), immunohistochemistry (IHC) and quantitative RT-PCR (qRT-PCR) in 173 selected advanced NSCLC patients. Clinicopathologic data, genotype status and survival outcomes were analyzed. Moreover, the association of ALK expression with clinical outcomes was evaluated in ALK FISH-positive crizotinib-treated patients including two patients with concurrent epidermal growth factor receptor (EGFR) mutation. Results The positivity detection rate of ALK rearrangement by FISH, IHC and qRT-PCR was 35.5% (59/166), 35.7% (61/171), and 27.9% (34/122), respectively. ALK rearrangement was observed predominantly in young patients, never or light smokers, and adenocarcinomas, especially with signet ring cell features and poor differentiation. Median progression-free survival (PFS) of crizotinib-treated patients was 7.6 months. The overall survival (OS) of these patients was longer compared with that of crizotinib-naive or wild-type cohorts, but there was no significant difference in OS compared with patients with EGFR mutation. ALK expression did not associate with PFS; but, when ALK expression was analyzed as a dichotomous variable, moderate and strong ALK expression had a decreased risk of death (P = 0.026). The two patients with concomitant EGFR and ALK alterations showed difference in ALK expression, response to EGFR and ALK inhibitors, and overall survival. Conclusions Selective enrichment according to clinicopathologic features in NSCLC patients could highly improve the positivity detection rate of ALK rearrangement for ALK-targeted therapy. IHC could provide more clues for clinical trial design and therapeutic strategies for ALK-positive NSCLC patients including patients with double genetic aberration of ALK and EGFR. PMID:24404167

[Expressions of heat shock protein (HSP) family HSP 60, 70 and 90alpha in colorectal cancer tissues and their correlations to pathohistological characteristics].

PubMed

Zhang, Wen-Li; Gao, Xue-Qin; Han, Jin-Xiang; Wang, Guo-Qiang; Yue, Long-Tao

2009-06-01

Colorectal cancer is the third common malignant tumor in the world. Heat shock protein (HSP) family has been reported to play an important role in carcinogenesis of various cancers. However, little is known about expressions of HSP60,HSP70 and HSP90alpha in colorectal cancer. This study was to investigate expressions of HSP 60, 70 and 90alpha, and analyzed their correlations to pathohistologic characteristics in colorectal cancer. Colorectal cancer tissues and adjacent normal tissues 2 cm away from the tumor focus were collected from 49 patients. Expressions of HSP60, HSP70 and HSP90alpha mRNA were detected by RT-PCR. The protein expressions of HSP60, HSP70 and HSP90alpha were determined by immunohistochemistry and western blot. The mRNA and protein levels of HSP60, HSP70 and HSP90alpha, as well as their positive rates were significantly increased in tumor tissues compared with those in para-cancerous tissues. The overexpression rates of HSP60, HSP70 and HSP90alpha were also significantly higher in the colorectal cancer tissues than those in the corresponding para-cancerous tissues. The positive and overexpression rates of HSP60, HSP70 and HSP90alpha in well, moderately and poorly differentiated colorectal cancer were not significantly different. HSP60, HSP70 and HSP90alpha may play important roles in the pathogenesis of colorectal cancer, although they are not correlated with the pathological grading.

[Clinical features and expression of PLA(2)R in renal tissue with idiopathic membranous nephropathy in children].

PubMed

Dong, Y F; Sun, L W; Zhang, B; Kuang, X Y; Niu, X L; Kang, Y L; Hao, S; Wang, P; Li, Z; Zhu, G H; Huang, W Y; Wu, Y

2018-03-02

Objective: To explore the clinical features and expression of PLA(2)R in renal tissue of children with idiopathic membranous nephropathy. Methods: Retrospective study was performed in patients with membranous nephropathy diagnosed through renal biopsy and the follow-up time was at least half a year in Shanghai Children ' s Hospital from January 2010 to February 2017. We compared their clinicopathological and pathological findings of IMN. Indirect immunofluorescence assay was used to detect glomerular PLA(2)R expression. We analyzed the differences of clinical features between the PLA(2)R negative and positive groups. T test, rank-sum test and Fisher exact test were used. Results: Eleven cases had hematuria and proteinuria, 9 cases presented with nephrotic syndrome, and 2 cases showed isolated proteinuria. Of the 22 cases of children with IMN, 16 patients had complete remission (complete remission rate was 72.8%), and 22 patients had partial remission. The renal function of all cases was normal and in all cases the estimated glomerular filtration rate was > 90 ml/(min·1.73m(2)). Of 22 cases with IMN, 7 cases were PLA(2)R-positive in renal tissue and 15 cases were PLA(2)R-negative. The age of positive group (10 years old) was older than the negative group (6 years old)( Z= -2.483, P< 0.05) and the time of positive group (6 months) for urine protein to return to negative was longer than the negative group (2.5 months) through treatment. These differences were significantly different ( Z= -2.072, P< 0.05). Conclusions: Hematuria and proteinuria can be found in most children with idiopathic primary membranous nephropathy. Prednisone combined with immunosuppressant was effective. The positive rate of PLA(2)R in renal tissue of children with IMN was about 32%. The age of PLA(2)R positive group was older than the negative group. And the time of urine protein turning to negative in positive group was longer than that in the negative group.

A non-randomized, open-label, single-arm, Phase 2 study of emibetuzumab in Asian patients with MET diagnostic positive, advanced gastric cancer.

PubMed

Sakai, Daisuke; Chung, Hyun Cheol; Oh, Do-Youn; Park, Se Hoon; Kadowaki, Shigenori; Kim, Yeul Hong; Tsuji, Akihito; Komatsu, Yoshito; Kang, Yoon-Koo; Uenaka, Kazunori; Wijayawardana, Sameera R; Wacheck, Volker; Wang, Xuejing; Yamamura, Ayuko; Doi, Toshihiko

2017-12-01

Mesenchymal-epithelial transition factor (MET) is expressed in gastric cancer and associated with poor clinical outcomes. We assessed activity, safety, and pharmacokinetics of emibetuzumab, a bivalent monoclonal anti-MET antibody that blocks ligand-dependent and ligand-independent MET signaling. This non-randomized, single-arm, Phase 2 study enrolled Asian patients with MET diagnostic positive advanced gastric adenocarcinoma. Emibetuzumab (2000 mg, intravenous) was given on days 1 and 15 (28-day cycle). The primary endpoint was 8-week progression-free survival rate. Secondary objectives included safety, pharmacokinetics, overall survival, and change in tumor size. Tumors from 65 patients were immunohistochemically screened to enroll 15 MET diagnostic positive patients (23% positivity; 8 Japanese, 7 Korean; 10 male). Eight-week progression-free survival rate was 0.47 (70% CI, 0.33-0.59). Disease control rate was 40% (target lesion decreases, three patients; no complete/partial responses according to RECIST). Median overall survival was 17.1 weeks (95% CI, 6.3-not achievable). No serious emibetuzumab-related adverse events or new safety signals emerged. Grade ≥ 3 possibly drug-related adverse events were hyperkalemia, hyponatremia, and hyperuricemia (one each). Emibetuzumab's pharmacokinetics profile was similar to that observed previously. MET expression and clinical outcomes were not obviously associated. Emibetuzumab was well tolerated with limited single-agent activity in advanced gastric adenocarcinoma.

Differentially expressed proteins among normal cervix, cervical intraepithelial neoplasia and cervical squamous cell carcinoma.

PubMed

Zhao, Q; He, Y; Wang, X-L; Zhang, Y-X; Wu, Y-M

2015-08-01

To explore the differentially expressed proteins in normal cervix, cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC) tissues by differential proteomics technique. Cervical tissues (including normal cervix, CIN and CSCC) were collected in Department of Gynecologic Oncology of Beijing Obstetrics and Gynecology Hospital. Two-dimensional fluorescence difference in gel electrophoresis (2-D DIGE) and DeCyder software were used to detect the differentially expressed proteins. Matrix-assisted laser desorption/ionization-time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS) was used to identify the differentially expressed proteins. Western blot (WB) and immunohistochemistry (IHC) were performed to validate the expressions of selected proteins among normal cervix, CIN and CSCC. 2-D DIGE images with high resolution and good repeatability were obtained. Forty-six differentially expressed proteins (27 up-regulated and 19 down-regulated) were differentially expressed among the normal cervix, CIN and CSCC. 26 proteins were successfully identified by MALDI-TOF/TOF MS. S100A9 (S100 calcium-binding protein A9) was the most significantly up-regulated protein. Eukaryotic elongation factor 1-alpha-1 (eEF1A1) was the most significantly down-regulated protein. Pyruvate kinase isozymes M2 (PKM2) was both up-regulated and down-regulated. The results of WB showed that with the increase in the severity of cervical lesions, the expression of S100A9 protein was significantly increased among the three groups (P = 0.010). The expression of eEF1A1 was reduced but without significant difference (P = 0.861). The expression of PKM2 was significantly reduced (P = 0.000). IHC showed that protein S100A9 was mainly expressed in the cytoplasm, and its positive expression rate was 20.0 % in normal cervix, 70.0 % in CIN and 100.0 % in CSCC, with a significant difference among them (P = 0.006). eEF1A1 was mainly expressed in the cell plasma, and its positive expression rate was 70.0 % in normal cervix, 73.3 % in CIN and 60.0 % in CSCC tissues, without significant difference among them (P = 0.758). PKM2 was mainly expressed in the cell nuclei, and its positive expression rate was 100.0 % in normal cervix, 93.3 % in CIN and 75.0 % in CSCC tissues, showing a difference close to statistical significance (P = 0.059) among them. There are differentially expressed proteins among normal cervix, CIN and CSCC. S100A9, eEF1A1 and PKM2 may become candidate markers for early diagnosis of cervical cancer and new targets for therapy. It also provides a basis for further studies of the mechanism for CIN developing to CSCC.

Positive bias is a defining characteristic of aging to the same extent as declining performance.

PubMed

Simón, Teresa; Suengas, Aurora G; Ruiz-Gallego-Largo, Trinidad; Bandrés, Javier

2013-01-01

The aim of this study was to analyze whether one of the supposed gains of aging--positive bias--discriminates between young and older participants to the same extent as some of the losses in cognitive performance--recall and source monitoring--that come with age. Two age groups (N = 120)--young (M = 22.08, SD = 3.30) and older (M = 72.78, SD = 6.57)--carried out three tasks with varying levels of difficulty that included recall, recognition, and source monitoring using pictures, faces, and personal descriptors exchanged in a conversation as stimuli. The results of the discriminant analysis performed on 20 dependent variables indicated that six of them were key in discriminating between young and older participants. Younger participants outperformed older participants in recalling pictures, and in recognizing the descriptors exchanged in a conversation, as well as in monitoring their source. Just as important in discriminating between the two groups were the ability to recognize previously seen pictures, the likability rating they produced, and the recognition of faces with positive expressions--all superior in older participants. Thus, variables related to a positive bias--likability ratings and recognition of positive expressions--characterize the differences as a function of age as well as variables related to cognitive performance, such as recall and source monitoring. In addition, the likability ratings evoked by both pictures and faces were also significantly higher in the older participants with better cognitive performance than in those who performed poorly. This effect was not present in younger participants. The results are interpreted within the framework of socioemotional selectivity theory as evidence for a positive bias in old age. The connection between a positive bias and the maintenance of cognitive performance is also discussed.

Elevated expression of matrix metalloproteinase-9 is associated with bladder cancer pathogenesis.

PubMed

Wu, Gong-Jin; Bao, Jun-Sheng; Yue, Zhong-Jin; Zeng, Fan-Chang; Cen, Song; Tang, Zheng-Yan; Kang, Xin-Li

2018-01-01

This study investigated the association between abnormal matrix metalloproteinase-9 (MMP-9) expression and bladder cancer (BC) development. In a retrospective analysis, this study used tissue samples derived from 92 patients pathologically diagnosed with BC (experimental group), who were hospitalized between September 2012 and June 2014 at the Urinary Surgery of Department of Urology, Lanzhou University Second Hospital. As controls (control group), 63 normal pericancerous bladder mucosal tissues (3 cm distant form edge of BC foci) with confirmed pathology were selected from the same time period. Immunohistochemistry was employed to detect MMP-9 protein expression in the tissues and enzyme-linked immunosorbent assay was performed to measure MMP-9 protein levels in tissue samples of patients and control subjects. Finally, a meta-analysis was conducted to understand the overall impact of MMP-9 on BC pathogenesis. STATA 12.0 software (Stata Corp, College Station, TX, USA) was used for all statistical analyses. The MMP-9 positive expression rate in tissue samples and MMP-9 levels were significantly greater in the experimental group compared to the control group (both P < 0.001). The frequency of MMP-9 positive status showed statistically significant differences between G1 (low-grade) and G3 (high-grade) (P < 0.001), between G2 and G3 (P < 0.05), and between G1/G2 and G3 (P = 0.001). Our meta-analysis findings provided further evidence that MMP-9 positive expression status and MMP-9 levels in the experimental group were significantly higher than the control group (positive expressions: Odds ratio [OR] = 18.59, 95% confidence interval [95% CI] = 11.63-29.71, P < 0.001; expression levels: Standard mean difference = 1.51, 95%CI = 0.63-2.39, P = 0.001). The positive expression status of MMP-9 was notably lower in G1/G2 compared to G3 (OR = 0.24, 95%CI = 0.15-0.36, P < 0.001). Our study demonstrated that both positive expression status in tumor tissue and expression levels of MMP-9 are significantly elevated in BC patients and correlate with disease progression. Thus, MMP-9 can serve as a biomarker to determine the degree of BC malignancy.

Human papillomavirus status and gene expression profiles of oropharyngeal and oral cancers from European American and African American patients.

PubMed

Tomar, Swati; Graves, Christian A; Altomare, Diego; Kowli, Sangeeta; Kassler, Susannah; Sutkowski, Natalie; Gillespie, M Boyd; Creek, Kim E; Pirisi, Lucia

2016-04-01

Disparities in prevalence, human papillomavirus (HPV) status, and mortality rates for head and neck cancer have been described between African American and European American patients. We studied the HPV status and gene expression profiles in 56 oropharyngeal/oral cavity tumors and 9 normal tissue samples from European American and African American patients treated in South Carolina between 2010 and 2012. Overall, 59% of tumors were HPV DNA-positive, but only 48% of those expressed E7 mRNA (HPV-active). The prevalence of HPV-active tumors was 10% in African American patients and 39% in European American patients. Tumors positive for HPV DNA but negative for HPV mRNA exhibited gene expression profiles distinct from those of both HPV-active and HPV-negative cancers, suggesting that HPV DNA-positive/RNA-negative tumors may constitute a unique group. This study provides a direct assessment of differential expression patterns in HPV-related oropharyngeal cancer arising from African American and European American patients, for which there is a paucity of data. © 2015 Wiley Periodicals, Inc. Head Neck 00: 000-000, 2015. © 2015 Wiley Periodicals, Inc.

Are patients with schizophrenia rational maximizers? Evidence from an ultimatum game study.

PubMed

Csukly, Gábor; Polgár, Patrícia; Tombor, László; Réthelyi, János; Kéri, Szabolcs

2011-05-15

Schizophrenia is associated with impaired social cognition and community functioning. Social decision-making strategies of healthy controls and patients with schizophrenia were compared by using the ultimatum game (UG). In this game two players have to split a sum of money. The proposer offers a portion to the responder, who decides to either accept or reject the offer. Rejection results in no income to either of the parties. Unfair proposals are frequently rejected by nonclinical individuals, a phenomenon described as altruistic punishment. Patients and controls participated in a series of UG interactions as responders in a computerized test setting. We also tested the effect of the proposer's facial expression on decision-making. Our results indicate that patients with schizophrenia accepted unfair offers at a significantly higher rate than did healthy controls. In contrast, at fair proposals, the acceptance rate was lower in patients compared with controls. At higher offers, the proposer's facial expression (positive/negative) significantly influenced the acceptance rate (positive facial expression increased the likelihood of acceptance) in the control group. This effect was not observed in the patient group. These results suggest that schizophrenia patients are impaired in socioeconomic interactions requiring emotion recognition and decision-making, which may result in unstable behavioral strategies. Copyright © 2010 Elsevier Ltd. All rights reserved.

Effects of Assertiveness Training and Expressive Writing on Acculturative Stress in International Students: A Randomized Trial

PubMed Central

Tavakoli, Shedeh; Lumley, Mark A.; Hijazi, Alaa M.; Slavin-Spenny, Olga M.; Parris, George P.

2010-01-01

International university students often experience acculturative stress, and culturally appropriate techniques to manage stress are needed. This randomized trial tested the effects of group assertiveness training, private expressive writing, their combination, and a wait-list control on the acculturative stress, affect, and health of 118 international students at an urban, American university. Interventions were conducted at the start of a semester, and assessments were conducted at baseline and the end of the semester. Group assertiveness training was rated positively by students and led to lower negative affect, whereas expressive writing was less well received and led to higher homesickness and fear, but also higher positive affect. The combined intervention had no effects, perhaps because the two components negated each other. It is concluded that group assertiveness training improves emotional adjustment of international students, but expressive writing has mixed effects and needs further development and study. PMID:20357910

Expression of Anti-apoptotic Protein BAG3 in Human Sebaceous Gland Carcinoma of the Eyelid.

PubMed

Yunoki, Tatsuya; Tabuchi, Yoshiaki; Hayashi, Atsushi

2017-04-01

Bcl-2-associated athanogene 3 (BAG3), a co-chaperone of heat shock protein 70 (HSP70), has been shown to play a role in anti-apoptosis of various malignant tumors. In this study, the expression of BAG3 was examined in human sebaceous gland carcinoma of the eyelid. The expression of BAG3 was evaluated by immunohistochemistry of surgical samples from 5 patients with sebaceous gland carcinoma in the eyelid. BAG3 was positive diffusely in the cytoplasm in all patients. The average positive rate of BAG3 was 73.0±26.0% in tumor cells of all patients. BAG3 was highly expressed in sebaceous gland carcinoma of the eyelid. BAG3 may play an important role in the pathogenesis and progression of sebaceous gland carcinoma of the eyelid. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Tissue microarray immunohistochemical detection of brachyury is not a prognostic indicator in chordoma.

PubMed

Zhang, Linlin; Guo, Shang; Schwab, Joseph H; Nielsen, G Petur; Choy, Edwin; Ye, Shunan; Zhang, Zhan; Mankin, Henry; Hornicek, Francis J; Duan, Zhenfeng

2013-01-01

Brachyury is a marker for notochord-derived tissues and neoplasms, such as chordoma. However, the prognostic relevance of brachyury expression in chordoma is still unknown. The improvement of tissue microarray technology has provided the opportunity to perform analyses of tumor tissues on a large scale in a uniform and consistent manner. This study was designed with the use of tissue microarray to determine the expression of brachyury. Brachyury expression in chordoma tissues from 78 chordoma patients was analyzed by immunohistochemical staining of tissue microarray. The clinicopathologic parameters, including gender, age, location of tumor and metastatic status were evaluated. Fifty-nine of 78 (75.64%) tumors showed nuclear staining for brachyury, and among them, 29 tumors (49.15%) showed 1+ (<30% positive cells) staining, 15 tumors (25.42%) had 2+ (31% to 60% positive cells) staining, and 15 tumors (25.42%) demonstrated 3+ (61% to 100% positive cells) staining. Brachyury nuclear staining was detected more frequently in sacral chordomas than in chordomas of the mobile spine. However, there was no significant relationship between brachyury expression and other clinical variables. By Kaplan-Meier analysis, brachyury expression failed to produce any significant relationship with the overall survival rate. In conclusion, brachyury expression is not a prognostic indicator in chordoma.

Cigarette smoke induces the expression of Notch3, not Notch1, protein in lung adenocarcinoma.

PubMed

Cheng, Zhenshun; Tan, Qiuyue; Tan, Weijun; Zhang, L I

2015-08-01

The aim of the present study was to determine the effect of cigarette smoke on the expression of Notch proteins in lung adenocarcinoma (LAC). Protein expression levels of Notch1 and Notch3 were analyzed using immunohistochemistry in 102 human LAC specimens. Of these, 52 were obtained from smokers and 50 from non-smokers. In addition, cigarette smoke extract (CSE) at varying concentrations (1, 2.5 and 5%) was administered to A549 cells. The expression of Notch1 and Notch3 protein was then detected by western blot analysis at different time points (0, 8, 24 and 48 h). Of the 102 LAC specimens, 42 (41.2%) were positive for Notch1 and 63 (61.8%) were positive for Notch3. There was no significant difference in the level of Notch1 expression between smokers and non-smokers with LAC (P>0.05). The positive rate and staining intensity of Notch3 expression were increased in the smokers compared with the non-smokers (P<0.05). The expression of Notch3 protein in A549 cells increased in a time- and dose-dependent manner following treatment with CSE, whilst the expression of Notch1 protein appeared stable. The results suggested that cigarette smoke was able to induce the expression of Notch3, not Notch1, protein in LAC. The data revealed an upregulation of Notch3 in LAC following cigarette smoke exposure. Such findings may provide a novel therapeutic target for the treatment of LAC.

FAP-1 and NF-κB expressions in oral squamous cell carcinoma as potential markers for chemo-radio sensitivity and prognosis.

PubMed

Nariai, Y; Mishima, K; Yoshimura, Y; Sekine, J

2011-04-01

This study was designed to investigate the feasibility of using Fas-associated phosphatase-1 (FAP-1), nuclear factor kappa B (NF-κB) and p53 as markers for chemo-radio sensitivity in oral squamous cell carcinoma (OSCC). FAP-1 plays a role as an anti-apoptotic factor through Fas-dependent apoptosis after chemo-radiotherapy. NF-κB and p53 might be involved in modulation of FAP-1 expression. FAP-1, NF-κB and p53 expression were immunohistochemically examined using biopsy specimens in 50 OSCC patients treated with chemotherapy and/or radiotherapy. FAP-1 was expressed in 52%, NF-κB in 52% and p53 in 46% of patients. There was no significant difference in FAP-1, p53 or NF-κB expression according to the clinicopathological features. No correlation was found among FAP-1, p53 or NF-κB expression. FAP-1-positive cases showed a poorer survival rate than FAP-1-negative cases (P = 0.0409) and NF-κB-positive cases showed a poorer survival rate than NF-κB-negative cases (P = 0.0018). Multivariate analysis showed that FAP-1 expression, NF-κB expression, clinical stage and age were significant independent variables for survival (clinical stage: P = 0.0016; age: P = 0.0016; NF-κB: P = 0.0314; FAP-1: P = 0.0366). These results suggest that FAP-1 and NF-κB might play a role as chemo-radioresistant factor during chemo-radiotherapy, and FAP-1 and NF-κB expression in OSCC would be feasible markers for chemo-radio sensitivity and prognosis. Copyright © 2010 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

The many faces of a face: Comparing stills and videos of facial expressions in eight dimensions (SAVE database).

PubMed

Garrido, Margarida V; Lopes, Diniz; Prada, Marília; Rodrigues, David; Jerónimo, Rita; Mourão, Rui P

2017-08-01

This article presents subjective rating norms for a new set of Stills And Videos of facial Expressions-the SAVE database. Twenty nonprofessional models were filmed while posing in three different facial expressions (smile, neutral, and frown). After each pose, the models completed the PANAS questionnaire, and reported more positive affect after smiling and more negative affect after frowning. From the shooting material, stills and 5 s and 10 s videos were edited (total stimulus set = 180). A different sample of 120 participants evaluated the stimuli for attractiveness, arousal, clarity, genuineness, familiarity, intensity, valence, and similarity. Overall, facial expression had a main effect in all of the evaluated dimensions, with smiling models obtaining the highest ratings. Frowning expressions were perceived as being more arousing, clearer, and more intense, but also as more negative than neutral expressions. Stimulus presentation format only influenced the ratings of attractiveness, familiarity, genuineness, and intensity. The attractiveness and familiarity ratings increased with longer exposure times, whereas genuineness decreased. The ratings in the several dimensions were correlated. The subjective norms of facial stimuli presented in this article have potential applications to the work of researchers in several research domains. From our database, researchers may choose the most adequate stimulus presentation format for a particular experiment, select and manipulate the dimensions of interest, and control for the remaining dimensions. The full stimulus set and descriptive results (means, standard deviations, and confidence intervals) for each stimulus per dimension are provided as supplementary material.

Role of central nervous system glucagon-like Peptide-1 receptors in enteric glucose sensing.

PubMed

Knauf, Claude; Cani, Patrice D; Kim, Dong-Hoon; Iglesias, Miguel A; Chabo, Chantal; Waget, Aurélie; Colom, André; Rastrelli, Sophie; Delzenne, Nathalie M; Drucker, Daniel J; Seeley, Randy J; Burcelin, Remy

2008-10-01

Ingested glucose is detected by specialized sensors in the enteric/hepatoportal vein, which send neural signals to the brain, which in turn regulates key peripheral tissues. Hence, impairment in the control of enteric-neural glucose sensing could contribute to disordered glucose homeostasis. The aim of this study was to determine the cells in the brain targeted by the activation of the enteric glucose-sensing system. We selectively activated the axis in mice using a low-rate intragastric glucose infusion in wild-type and glucagon-like peptide-1 (GLP-1) receptor knockout mice, neuropeptide Y-and proopiomelanocortin-green fluorescent protein-expressing mice, and high-fat diet diabetic mice. We quantified the whole-body glucose utilization rate and the pattern of c-Fos positive in the brain. Enteric glucose increased muscle glycogen synthesis by 30% and regulates c-Fos expression in the brainstem and the hypothalamus. Moreover, the synthesis of muscle glycogen was diminished after central infusion of the GLP-1 receptor (GLP-1Rc) antagonist Exendin 9-39 and abolished in GLP-1Rc knockout mice. Gut-glucose-sensitive c-Fos-positive cells of the arcuate nucleus colocalized with neuropeptide Y-positive neurons but not with proopiomelanocortin-positive neurons. Furthermore, high-fat feeding prevented the enteric activation of c-Fos expression. We conclude that the gut-glucose sensor modulates peripheral glucose metabolism through a nutrient-sensitive mechanism, which requires brain GLP-1Rc signaling and is impaired during diabetes.

[Research on the expression of Survivin and PTEN in laryngeal squamous cell carcinoma transplanted on the back sides of nude mice treated by gold throat tablets].

PubMed

Guo, Qiangzhong; Li, Yunying

2012-12-01

To explore the positive expressing rates of oncogene Survivin and tumor-suppressor gene PTEN in transplanted laryngo-carcinoma of nude mice treated by Gold Throat Tablets (GTT) which can improve circulation and remove haemostasis in TCM theory. The 32 nude mice seeded with cultured laryngeal carcinoma cells subcutaneously at the back were randomly divided into high, middle, low (according to 6 : 3: 1 proportion of GTT dosing given by intragastric administration) dose groups and blank control groups. The changes on weight and size of tumors originated from these cells were observed for 28 days, and the density of tumors and expression of Survivin and PTEN were examined with tumor sections by immunohistochemical assay after separating tumors from back of nude mice. The weight and size of subcutaneous laryngo-carcinoma on backs of high dose group nude mice were both the smallest among all the experimental groups with the average density of tumors as 1.202 g/cm3. The positive expressing rates of Survivin and PTEN both revealed the following tendency that high dose group < middle dose group < low dose group < blank control group. Six times of regular doses of GTT can prevent overgrowth of laryngo-carcinoma transplanted on nude mice and decrease the excessive expression of oncogene Survivin in the tumor. PTEN, expressing lower than Survivin in all groups, shows a subordinative relationship with it, maybe due to a competition mechanism.

HPV16 E6 regulates annexin 1 (ANXA1) protein expression in cervical carcinoma cell lines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Calmon, Marilia Freitas; Sichero, Laura; Boccardo, Enrique

Annexin 1 (ANXA1) is a substrate for E6AP mediated ubiquitylation. It has been hypothesized that HPV 16 E6 protein redirects E6AP away from ANXA1, increasing its stability and possibly contributing to viral pathogenesis. We analyzed ANXA1 expression in HPV-positive and negative cervical carcinoma-derived cells, in cells expressing HPV-16 oncogenes and in cells transduced with shRNA targeting E6AP. We observed that ANXA1 protein expression increased in HPV-16-positive tumor cells, in keratinocytes expressing HPV-16 E6wt (wild-type) or E6/E7 and C33 cells expressing HPV-16 E6wt. ANXA1 protein expression decreased in cells transfected with E6 Dicer-substrate RNAs (DsiRNA) and C33 cells cotransduced with HPV-16more » E6wt and E6AP shRNA. Moreover, colony number and proliferation rate decreased in HPV16-positive cells transduced with ANXA1 shRNA. We observed that in cells infected with HPV16, the E6 binds to E6AP to degrade p53 and upregulate ANXA1. We suggest that ANXA1 may play a role in HPV-mediated carcinogenesis. - Highlights: • ANXA1 upregulation requires the presence of E6 and E6AP and is dependent on E6 integrity. • E6 binds to E6AP to degrade p53 and upregulate ANXA1 in cells infected with HPV16. • ANXA1 plays a role in cell proliferation in HPV-positive cervical cells.« less

Exposure to bisphenol A (BPA) in Wistar rats reduces sperm quality with disruption of ERK signal pathway.

PubMed

Li, Juan; Mao, Rui; Zhou, Qin; Ding, Ling; Tao, Jin; Ran, Mao-Mei; Gao, Er-Sheng; Yuan, Wei; Wang, Jin-Tao; Hou, Li-Fang

2016-01-01

Bisphenol A (BPA) is an estrogenic environmental toxin widely used in the production of plastics and ubiquitous human exposure to this chemical has been proposed to be a potential risk to human health. Exposure to BPA can negatively impact sperm quality. However, the mechanism remains largely unknown. The objectives of this study were to assess the role of BPA on sperm quality and explore the possible mechanisms. The Wistar male rats (aged 28 days) were administered BPA by oral gavage for 28 days at dose of 50, 100 and 200 mg/kg/day; meanwhile, the negative control with corn oil (0 mg/kg/day BPA) and positive control with E2 at the dose of 100 μg/kg/day. The sperm density, sperm activity and sperm survival rate were analyzed byCASA system, and the sperm abnormality rate was analyzed by improved Papanicolaou stained. The protein expression levels of Src/p-Src, ERK1/2, p-ERK1/2 and CREB/p-CREB were detected by Western bolt. The results showed that the body weight gain, testes weight, testis coefficient, sperm density, sperm activity, sperm survival rate and protein expression levels of p-ERK1, p-ERK2 and p-CREB decreased, but the sperm abnormality rate increased with increasing BPA concentrations. There were positive correlations between sperm density, sperm activity and sperm survival rate with protein expression levels of p-ERK1, p-ERK2 and p-CREB, and negative correlations between sperm abnormality rate with the protein expression levels of p-ERK1, p-ERK2 and p-CREB. Results from the structural equation model demonstrated that BPA retained a significant negative effect to p-ERK, whereas p-ERK retained a significant positive effect to sperm quality and acted as the mediate variable. This study provides a novel insight regarding the potential role of p-ERK1 and p-ERK2 protein kinase on reproductive toxicity of BPA. The adverse effects of BPA on adult male sperm quality may be through the induction of the disruption of ERK signal pathway. However, additional research is needed to confirm our findings and to further test the suggested potential mechanisms.

Expression of granulocyte colony-stimulating factor receptor correlates with prognosis in oral and mesopharyngeal carcinoma.

PubMed

Tsuzuki, H; Fujieda, S; Sunaga, H; Noda, I; Saito, H

1998-02-15

Granulocyte colony-stimulating factor receptors (G-CSFRs) have been observed on the surface of not only hematopoietic cells but also several cancer cells. The stimulation of G-CSF has been demonstrated to induce proliferation and activation of G-CSFR-positive cells. In this study, we investigated the expression of G-CSFR on the surface of tumor cells and G-CSF production in oral and mesopharyngeal squamous cell carcinoma (SCC) by an immunohistochemical approach. Of 58 oral and mesopharyngeal SCCs, 31 cases (53.4%) and 36 cases (62.1%) were positive for G-CSFR and G-CSF, respectively. There was no association between G-CSFR expression and G-CSF staining. In the group positive for G-CSFR expression, relapse was significantly more likely after primary treatment (P = 0.0069), whereas there was no association between G-CSFR expression and age, sex, tumor size, lymph node metastasis, and clinical stage. Also, the G-CSFR-positive groups had a significantly lower disease-free and overall survival rate than the G-CSFR-negative groups (P = 0.0172 and 0.0188, respectively). However, none of the clinical markers correlated significantly with G-CSF staining, nor did the status of G-CSF production influence the overall survival. The results imply that assessment of G-CSFR may prove valuable in selecting patients with oral and mesopharyngeal SCC for aggressive therapy.

[Effect of Jianpi Yangzheng Xiaozheng Recipe on Apoptosis and Autophagy of Subcutaneous Transplanted Tumor in Nude Mice: an Experimental Study on Mechanism].

PubMed

Wu, Jian; Liu, Shen-lin; Zhang, Xing-xing; Chen, Min; Zou, Xi

2015-09-01

To observe the effect of Jianpi Yangzheng Xiaozheng Recipe (JYXR) on the tumor inhibition rate of subcutaneous transplanted tumor gastric cancer cell line MGC-803 in BALB/c nude mice, and to study its molecular mechanism of apoptosis and autophagy. Gastric cancer cell line MGC-803 was subcutaneously inoculated to nude mice for preparing transplanted gastric cancer models. Totally 32 BALB/c nude mice were randomly divided into 4 groups according to random digit table, i.e., the negative control group, the positive control group, the high dose JYXR group, the low dose JYXR group, 8 in each group. Normal saline was administered to mice in the negative control group by gastrogavage. 5-fluorouracil (5-Fu) at 2. 5 mg/kg was administered to mice in the positive control group by gastrogavage. JYXR at 85 and 43 g/kg was administered to mice in the high dose JYXR group and the low dose JYXR group by gastrogavage, once per day for 10 successive days. The effect of JYXR on the tumor inhibition rate of subcutaneous transplanted tumor was observed. Effects of JYXR on gene expression levels of Bax, Bcl-2, Fas, Cyclin D1, Cyclin D2, and Cyclin D3 in transplanted tumor were observed by real-time PCR. Effects of JYXR on protein expression levels of Procaspase-3, Procaspase-8, Procaspase-9, cleaved-PARP, Beclin-1, and LC3B were detected using Western blot. (1) Compared with the negative control group, the tumor weight was obviously reduced in the rest three groups (P <0. 05). The tumor weight was higher in the high dose JYXR group and the low dose JYXR group than in the positive control group (P <0. 05). (2) Results of RT-PCR indicated that, compared with the negative control group, expression levels of Bax were up-regulated, but expression levels of Bcl-2, Cyclin D1, Cyclin D2, and Cyclin D3 were down-regulated in the positive control group and JYXR groups (P <0. 05). The expression level of Fas was up-regulated in the positive control group and the high dose JYXR group (P <0. 05). Compared with the positive control group, expression levels of Fas, and Bax were all down-regulated, but expression levels of Bcl-2, Cyclin D2, and Cyclin D3 were all up-regulated in the high dose JYXR group and the low dose JYXR group (all P <0. 05). The expression level of Cyclin D1 was down-regulated in the high dose JYXR group, but it was up-regulated in the low dose JYXR group ( both P <0. 05). (3) Results of Western blot showed, compared with the negative control group, expression levels of Procaspase-3, Procaspase-8, and Procaspase-9 were down-regulated, but expression levels of cleaved-PARP, Beclin-1, and LC3B II were up-regulated in the high dose JYXR group and the low dose JYXR group (all P <0.05). Compared with the negative control group, expression levels of Procaspase-3, Procaspase-8, Procaspase-9, and LC3B II were down-regulated, but expression levels of cleaved-PARP, Beclin-1, and LC3B I were up-regulated in the positive control group (all P <0. 05). JYXR showed significant inhibition on subcutaneous transplanted tumor gastric cancer cell line MGC-803 in BALB/c nude mice. Its mechanism might be associated with activating apoptosis and autophagy correlated factors.

Prothymosin-α and parathymosin expression predicts poor prognosis in squamous and adenosquamous carcinomas of the gallbladder

PubMed Central

Chen, Kang; Xiong, Li; Yang, Zhuling; Huang, Shengfu; Zeng, Rong; Miao, Xiongying

2018-01-01

The present study aimed to investigate the expression patterns of prothymosin-α (PTMA) and parathymosin (PTMS) in patients with squamous cell carcinoma (SCC), adenosquamous cell carcinoma (ASC) and adenocarcinoma (AC) of the gallbladder, and to assess their association with the clinicopathological characteristics and prognosis of the patients. A retrospective analysis of data pertaining to patients with SCC/ASC (n=46) and AC (n=80) of the gallbladder, who were treated with surgical resection, was conducted. Kaplan-Meier survival analysis was also performed to assess the correlation of the expression pattern with survival. The results revealed a higher percentage of patients with a large tumor diameter (>3 cm) in the SCC/ASC group as compared with those in the AC group (P<0.05). No significant differences were observed between patients with SCC/ASC and those with AC with respect to the patient sex, presence of gallstones, TNM stage, lymph node metastasis, invasive growth into anatomically contiguous structures, surgical methods used, survival rate, and the expression levels of PTMA and PTMA (P>0.05). However, positive expression of PTMA and PTMA was associated with tumor size, TNM stage, lymph node metastasis, locally invasive growth, and treatment with radical resection in patients with SCC/ASC and AC (P<0.05). In addition, positive expression of PTMA and PTMA was observed in a significantly lower number of patients with advanced AC as compared with those in early AC (P<0.05), while these expression levels were also associated with shorter survival in the SCC/ASC group and AC group (P<0.05). Cox multivariate analysis also demonstrated a negative correlation between PTMA and PTMA levels, and the postoperative survival rate in the two groups. In conclusion, the present study indicated that the expression levels of PTMA and PTMA were closely associated with the tumorigenesis and progression of SCC, ASC and AC of the gallbladder. Positive expression of PTMA and PTMA may serve as a valuable prognostic factor in these patients. PMID:29541218

Clinical significance of HOX11L2 expression linked to t(5;14)(q35;q32), of HOX11 expression, and of SIL-TAL fusion in childhood T-cell malignancies: results of EORTC studies 58881 and 58951.

PubMed

Cavé, Hélène; Suciu, Stefan; Preudhomme, Claude; Poppe, Bruce; Robert, Alain; Uyttebroeck, Anne; Malet, Michèle; Boutard, Patrick; Benoit, Yves; Mauvieux, Laurent; Lutz, Patrick; Méchinaud, Françoise; Grardel, Nathalie; Mazingue, Francoise; Dupont, Madeleine; Margueritte, Geneviève; Pages, Marie-Pierre; Bertrand, Yves; Plouvier, Emmanuel; Brunie, Ghislaine; Bastard, Christian; Plantaz, Dominique; Vande Velde, Isabel; Hagemeijer, Anne; Speleman, Frank; Lessard, Michel; Otten, Jacques; Vilmer, Etienne; Dastugue, Nicole

2004-01-15

In a series of 153 children with T-cell malignancies enrolled in 2 consecutive European Organization for Research and Treatment of Cancer (EORTC) trials, we assessed the HOX11L2 expression and/or the presence of a t(5;14)(q35;q32). Additionally, in 138 of these patients, HOX11 expression and SIL-TAL rearrangement were also assessed. These alterations were mutually exclusive, and their frequency was 23% (n = 35), 7% (n = 10), and 12% (n = 17), respectively. HOX11L2/t(5;14) positivity was more frequent in acute lymphoblastic leukemia (ALL) with cortical T immunophenotype and in children aged between 6 and 9 years. In contrast with previously reported data, patients positive and negative for HOX11L2/t(5;14) were comparable with regard to clinical outcome as well as to the response to a 7-day prephase treatment or to residual disease at completion of induction therapy. The 3-year event-free survival (EFS) rate (+/- SE percentage) for patients positive and negative for HOX11L2/t(5;14) was 75.5% (+/- 8.1%) and 68.3% (+/- 5.0%), respectively; the hazard ratio was 0.84 (95% confidence interval, 0.40-1.80). Patients with HOX11-high expression and those with SIL-TAL fusion had low levels of residual disease at the end of induction and a favorable prognosis: the 3-year EFS rate was 83.3% (+/- 8.5%) and 75.3% (+/- 12.6%), respectively. The results obtained in HOX11L2/t(5;14) patients in this study do not confirm the unfavorable prognosis reported in previous studies.

Expression of survivin and p53 in oral lichen planus, lichenoid reaction and lichenoid dysplasia: An immunohistochemical study

PubMed Central

Basheer, Shaini; Shameena, PM; Sudha, S; Varma, Sujatha; Vidyanath, S; Varekar, Aniruddha

2017-01-01

Context: The malignant transformation potential of oral lichen planus (OLP) and related lesions is a subject of great controversy. Aim: The aim of this study was to compare the expression of proteins related to apoptosis and tumour suppressor gene processes in OLP, oral lichenoid reaction (OLR) and oral lichenoid dysplasia (OLD). Materials and Methods The immunohistochemical study was carried out to investigate the expressions of survivin and p53 in a total of 30 lesional biopsy specimens - 10 cases each of OLP, OLR and OLD. The expression rates were further compared with 10 control specimens of normal oral mucosa (NORM). Results: Immunoreactivity for p53 was seen in 7 cases (70%) of OLD, 4 cases (40%) of OLP and 2 cases (20%) of OLR and none of NORM. We obtained a significant difference (P = 0.01) in mean p53 expression between the different entities. The positive staining rate of survivin was found to be significantly different between OLD (50%), OLP (10%), OLR (0%), and normal mucosa (0%) (P = 0.004). There was a positive correlation between p53 and survivin expression in OLP and OLD using Pearson's correlation coefficient. Conclusion: Lichenoid dysplasia has shown p53 and survivin expression in the range of not OLP, but leukoplakia. On the other hand, OLR seems to be an innocuous lesion. The study results with OLP are inconclusive but points toward a small but important malignant potential in OLP. This kind of comparative study highlights the importance of biopsying OLP and related lesions for proper diagnosis and appropriate management. PMID:29391729

Expression patterns of lectin-like natural killer receptors, inhibitory CD94/NKG2A, and activating CD94/NKG2C on decidual CD56bright natural killer cells differ from those on peripheral CD56dim natural killer cells.

PubMed

Kusumi, Maki; Yamashita, Takahiro; Fujii, Tomoyuki; Nagamatsu, Takeshi; Kozuma, Shiro; Taketani, Yuji

2006-06-01

The balance of inhibitory and activating natural killer (NK) receptors on maternal decidual NK cells, most of which are CD56bright, is thought to be crucial for the proper growth of trophoblasts in placenta. A lectin-like NK receptor, CD94/NKG2, is the receptor for human leukocyte antigen (HLA)-E, which is expressed on trophoblasts. To clarify the mechanism regulating the activity of decidual NK cells during pregnancy, we investigated the expression patterns of inhibitory NK receptor, CD94/NKG2A, and activating receptor, CD94/NKG2C, on decidual NK cells in an early stage of normal pregnancy and compared them with those on peripheral NK cells, most of which are CD56dim. The rate of NKG2A-positive cells was significantly higher for decidual CD56bright NK cells than for peripheral CD56dim NK cells, but the rates of NKG2C-positive cells were comparable between the two cell types. Interestingly, peripheral CD56dim NK cells reciprocally expressed inhibitory NKG2A and activating NKG2C, but decidual CD56bright NK cells that expressed activating NKG2C simultaneously expressed inhibitory NKG2A. The co-expression of inhibitory and activating NKG2 receptors may fine-tune the immunoregulatory functions of the decidual NK cells to control the trophoblast invasion in constructing placenta.

[Correlation of chromosome 1p and 19q status and expression of R132H mutant IDH1 protein in oligodendroglial tumors].

PubMed

Yao, Kun; Duan, Zejun; Hu, Zeliang; Bian, Yu; Qi, Xueling

2014-10-01

To correlate the presence of chromosome 1p/19q deletion with the expression of R132H mutant IDH1 status in oligodendroglial tumors, and to explore molecular markers for predicting chemosensitivity of oligodendroglial tumors. The study included 75 oligodendroglial tumors (38 oligodendrogliomas and 37 oligoastrocytomas). Immunohistochemistry was used to detect the expression of R132H mutant IDH1 protein, and fluorescence in situ hybridization (FISH) was employed to detect 1p/19q deletion. Deletion of chromosome 1p and/or 19q was detected in 37 cases (37/75, 49.3%), among which co-deletion of 1p and 19q was seen in 34 cases (closely correlated, P < 0.01). Oligodendrogliomas WHOIIhad a slightly higher deletion rate than oligodendrogliomas WHO III, although without statistical significance. Oligodendrogliomas WHO IIand WHO III had a significantly higher deletion rate of chromosome 1p/19q than oligoastrocytomas WHO II and WHO III (P < 0.05). While combined loss of 1p/19q was always detected in oligodendrogliomas when FISH was positive, isolated 1p or 19q deletion was only found in oligoastrocytomas. The expression of R132H mutant IDH1 was detected in 51 of 75 cases (68.0%), in which oligodendrogliomas had a higher positive rate than oligoastrocytomas. Statistical analysis demonstrated a significant correlation between the expression of R132H mutant IDH1 protein and the presence of combined 1p/19q deletion in oligodendrogliomas (P < 0.05). A significant correlation was observed between the expression of R132H mutant protein and 1p/19q LOH.Expression of 132H mutant IDH1 protein is the potential biomarker for predicating the presence of 1p/19q deletion in oligodendrogliomas.

[Expression of connective tissue growth factor (CTGF), osteopontin (OPN) and clinical significances in the laryngeal squamous cell carcinoma tissues].

PubMed

Li, Youzhong; Lu, Yongde; Ceng, Yici; Yang, Xinming

2007-02-01

To study the expressions of CTGF and OPN and detect their clinical value and correlation in the laryngeal squamous cell carcinoma tissues and paracancerous tissues. SP immunohistochemical method was used for the assays of CTGF and OPN on the routinely paraffin-embedded sections of surgical operated specimens of 41 cases with laryngeal squamous cell carcinoma and 20 ones with paracancerous tissues. The positive rate of CTGF and the score were significantly lower in cancer tissues than those in paracancerous tissues (61.0% vs 90.0%, P < 0.05; 2.41 +/- 1.60 vs 4.24 +/- 1.42, P < 0.01), but those of OPN were opposite (61.0% vs 15.0%, P < 0.01; 3. 10 +/- 1.63 vs 1.12 +/- 0.84, P < 0.01). The positive rates and scores of CTGF were significantly higher in the cases without-metastasis of lymph node and clinical stage T1 than those in the ones with-metastasis of lymph node and clinical stage T3 (P < 0.01) . The positive rates and scores of OPN were significantly lower in the cases without-metastasis of lymph node, clinical stage T1 and histological grade I those that in the ones with-metastasis of lymph node, Clinical stage T3 and histological grade III (P < 0.01). The closely negative correlation was found between the score of CTGF and that of OPN. The expression of CTGF and/or OPN might be important biological markers in reflecting the progression, biological behaviors, metastatic potential and prognosis of the laryngeal squamous cell carcinoma.

MASTERS OF ANALYTICAL TRADECRAFT: CERTIFYING THE STANDARDS AND ANALYTIC RIGOR OF INTELLIGENCE PRODUCTS

DTIC Science & Technology

2016-04-01

Disclaimer The views expressed in this academic research paper are those of the author and do not reflect the official policy or position of the US...10 Figure 2: Proposed MAT Rating Badges..............................................................................16...establishing unit level certified Masters of Analytic Tradecraft (MAT) analysts to be trained and entrusted to evaluate and rate the standards and

Altered iron metabolism, inflammation, transferrin receptors, and ferritin expression in non-small-cell lung cancer.

PubMed

Kukulj, Suzana; Jaganjac, Morana; Boranic, Milivoj; Krizanac, Simun; Santic, Zarko; Poljak-Blazi, Marija

2010-06-01

The involvement of iron and inflammation parameters on overall survival in non-small-cell lung cancer (NSCLC) patients was studied. Furthermore, transferrin receptors 1 (TfR1) and ferritin expression in tumor tissue, tumor stroma, and normal lung tissue were analyzed. Iron metabolism and inflammation parameters were determined by automated laboratory measurements at the time of diagnosis. TfR1 and ferritin expression were determined by immuno-histochemical methods. About 50% of patients survived 12 months only. At the time of diagnosis more than half of the patients had anemia and significantly elevated serum ferritin. Iron content of serum ferritin (ICF) was below the reference values in 90% of patients. Furthermore, ICF showed positive correlation with iron metabolic parameters and survival but negative correlation with serum ferritin and ESR. The expression of TfR1 and ferritin in tumor cells was observed in 88% or 62% of patients, respectively. Tumor stroma was TfR1 negative and sporadically ferritin positive. Tumor tissue ferritin expression showed negative correlation with serum iron and hematokrit (Ht), and positive correlation with ferritin, erythrocyte sedimentation rate (ESR), alpha-1 globulin, and alpha-2 globulin. Positive correlation was found between TfR1 expression in tumor tissue and alpha-globulin. The correlation between TfR1/ferritin expression in tumor tissue and ICF or survival was not observed. Therefore, we conclude that elevated serum ferritin in sera of NSCLC patients is the result of inflammation and oxidative stress rather than body iron overload. Higher expression of ferritin in tumor tissue may be the consequence of iron deficiency or local toxicity induced by environmental factors.

Clinical Significance of SASH1 Expression in Glioma

PubMed Central

Yang, Liu; Zhang, Haitao; Yao, Qi; Yan, Yingying; Wu, Ronghua; Liu, Mei

2015-01-01

Objective. SAM and SH3 domain containing 1 (SASH1) is a recently discovered tumor suppressor gene. The role of SASH1 in glioma has not yet been described. We investigated SASH1 expression in glioma cases to determine its clinical significance on glioma pathogenesis and prognosis. Methods. We produced tissue microarrays using 121 patient-derived glioma samples and 30 patient-derived nontumor cerebral samples. Immunohistochemistry and Western blotting were used to evaluate SASH1 expression. We used Fisher's exact tests to determine relationships between SASH1 expression and clinicopathological characteristics; Cox regression analysis to evaluate the independency of different SASH1 expression; Kaplan-Meier analysis to determine any correlation of SASH1 expression with survival rate. Results. SASH1 expression was closely correlated with the WHO glioma grade. Of the 121 cases, 66.9% with low SASH1 expression were mostly grade III-IV cases, whereas 33.1% with high SASH1 expression were mostly grades I-II. Kaplan-Meier analysis revealed a significant positive correlation between SASH1 expression and postoperative survival. Conclusions. SASH1 was widely expressed in normal and low-grade glioma tissues. SASH1 expression strongly correlated with glioma grades, showing higher expression at a lower grade, which decreased significantly as grade increased. Furthermore, SASH1 expression was positively correlated with better postoperative survival in patients with glioma. PMID:26424902

Emotional expression and heart rate in high-risk infants during the face-to-face/still-face.

PubMed

Mattson, Whitney I; Ekas, Naomi V; Lambert, Brittany; Tronick, Ed; Lester, Barry M; Messinger, Daniel S

2013-12-01

In infants, eye constriction-the Duchenne marker-and mouth opening appear to index the intensity of both positive and negative facial expressions. We combined eye constriction and mouth opening that co-occurred with smiles and cry-faces (respectively, the prototypic expressions of infant joy and distress) to measure emotional expression intensity. Expression intensity and heart rate were measured throughout the face-to-face/still-face (FFSF) in a sample of infants with prenatal cocaine exposure who were at risk for developmental difficulties. Smiles declined and cry-faces increased in the still-face episode, but the distribution of eye constriction and mouth opening in smiles and cry-faces did not differ across episodes of the FFSF. As time elapsed in the still face episode potential indices of intensity increased, cry-faces were more likely to be accompanied by eye constriction and mouth opening. During cry-faces there were also moderately stable individual differences in the quantity of eye constriction and mouth opening. Infant heart rate was higher during cry-faces and lower during smiles, but did not vary with intensity of expression or by episode. In sum, infants express more intense negative affect as the still-face progresses, but do not show clear differences in expressive intensity between episodes of the FFSF. Copyright © 2013 Elsevier Inc. All rights reserved.

Carabelli's trait in contemporary Slovenes and inhabitants of a medieval settlement (Sredisce by the Drava River).

PubMed

Stamfelj, Iztok; Stefancić, Marija; Gaspersic, Dominik; Cvetko, Erika

2006-06-01

The objectives of this study were to determine the total frequency, expression and asymmetry of Carabelli's trait in permanent dentitions of contemporary Slovenes and a medieval skeletal population from northeastern Slovenia. A total of 254 dental casts from contemporary Slovene children were examined. The population of a medieval settlement (10th-15th centuries), was represented by 94 skeletons. A modification of the method of Alvesalo and associates was used to classify Carabelli's trait on a five-grade scale. The trait was expressed on the upper first molars of 79.7% of the contemporary subjects and 75.8% of the medieval sample. Positive expressions of the trait were found in 10.1% of the contemporary subjects and 15.2% of the medieval sample. While the observed total frequency of the trait in both samples is characteristic of Europeans, the rates of positive expressions are surprisingly low but consistent with data from a recently published worldwide literature survey. Both populations showed a low rate of left-right fluctuating asymmetry of the trait. This finding might reflect a pronounced ability of individuals in the medieval population to buffer unfavourable influences from the environment and a relatively low level of environmental stress in the contemporary population.

Predictive value of EGFR overexpression and gene amplification on icotinib efficacy in patients with advanced esophageal squamous cell carcinoma

PubMed Central

Fan, Qingxia; Lu, Ping; Ma, Changwu; Liu, Wei; Liu, Ying; Li, Weiwei; Hu, Shaoxuan; Ling, Yun; Guo, Lei; Ying, Jianming; Huang, Jing

2016-01-01

This study aimed to search for a molecular marker for targeted epithelial growth factor receptor (EGFR) inhibitor Icotinib by analyzing protein expression and amplification of EGFR proto-oncogene in esophageal squamous cell carcinoma (ESCC) patients. Immunohistochemistry and fluorescence in situ hybridization (FISH) was used to assess EGFR expression and gene amplification status in 193 patients with ESCC. We also examined the association between EGFR overexpression and the efficacy of a novel EGFR TKI, icotinib, in 62 ESCC patients. Of the 193 patients, 95 (49.2%) patients showed EGFR overexpression (3+), and 47(24.4%) patients harbored EGFR FISH positivity. EGFR overexpression was significantly correlated with clinical stage and lymph node metastasis (p<0.05). In addition, EGFR overexpression was significantly correlated with EGFR FISH positivity (p<0.001). Among the 62 patients who received icotinib, the response rate was 17.6% for patients with high EGFR-expressing tumors, which was markedly higher than the rate (0%) for patients with low to moderate EGFR-expressing tumors (p=0.341). Furthermore, all cases responded to icotinib showed EGFR overexpression. In conclusion, our study suggests that EGFR overexpression might potentially be used in predicting the efficacy in patients treated with Icotinib. These data have implications for both clinical trial design and therapeutic strategies. PMID:27013591

Predictive value of EGFR overexpression and gene amplification on icotinib efficacy in patients with advanced esophageal squamous cell carcinoma.

PubMed

Wang, Xi; Niu, Haitao; Fan, Qingxia; Lu, Ping; Ma, Changwu; Liu, Wei; Liu, Ying; Li, Weiwei; Hu, Shaoxuan; Ling, Yun; Guo, Lei; Ying, Jianming; Huang, Jing

2016-04-26

This study aimed to search for a molecular marker for targeted epithelial growth factor receptor (EGFR) inhibitor Icotinib by analyzing protein expression and amplification of EGFR proto-oncogene in esophageal squamous cell carcinoma (ESCC) patients.Immunohistochemistry and fluorescence in situ hybridization (FISH) was used to assess EGFR expression and gene amplification status in 193 patients with ESCC. We also examined the association between EGFR overexpression and the efficacy of a novel EGFR TKI, icotinib, in 62 ESCC patients.Of the 193 patients, 95 (49.2%) patients showed EGFR overexpression (3+), and 47(24.4%) patients harbored EGFR FISH positivity. EGFR overexpression was significantly correlated with clinical stage and lymph node metastasis (p<0.05). In addition, EGFR overexpression was significantly correlated with EGFR FISH positivity (p<0.001). Among the 62 patients who received icotinib, the response rate was 17.6% for patients with high EGFR-expressing tumors, which was markedly higher than the rate (0%) for patients with low to moderate EGFR-expressing tumors (p=0.341). Furthermore, all cases responded to icotinib showed EGFR overexpression.In conclusion, our study suggests that EGFR overexpression might potentially be used in predicting the efficacy in patients treated with Icotinib. These data have implications for both clinical trial design and therapeutic strategies.

Assessing differential gene expression with small sample sizes in oligonucleotide arrays using a mean-variance model.

PubMed

Hu, Jianhua; Wright, Fred A

2007-03-01

The identification of the genes that are differentially expressed in two-sample microarray experiments remains a difficult problem when the number of arrays is very small. We discuss the implications of using ordinary t-statistics and examine other commonly used variants. For oligonucleotide arrays with multiple probes per gene, we introduce a simple model relating the mean and variance of expression, possibly with gene-specific random effects. Parameter estimates from the model have natural shrinkage properties that guard against inappropriately small variance estimates, and the model is used to obtain a differential expression statistic. A limiting value to the positive false discovery rate (pFDR) for ordinary t-tests provides motivation for our use of the data structure to improve variance estimates. Our approach performs well compared to other proposed approaches in terms of the false discovery rate.

14-3-3ε Overexpression Contributes to Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma

PubMed Central

Liang, Shu-Man; Chen, Shyh-Chang; Wang, John; Hsu, Chiun; Wu, Yao-Ming; Liou, Jun-Yang

2013-01-01

Background 14-3-3ε is implicated in regulating tumor progression, including hepatocellular carcinoma (HCC). Our earlier study indicated that elevated 14-3-3ε expression is significantly associated with higher risk of metastasis and lower survival rates of HCC patients. However, the molecular mechanisms of how 14-3-3ε regulates HCC tumor metastasis are still unclear. Methodology and Principal Findings In this study, we show that increased 14-3-3ε expression induces HCC cell migration and promotes epithelial-mesenchymal transition (EMT), which is determined by the reduction of E-cadherin expression and induction of N-cadherin and vimentin expression. Knockdown with specific siRNA abolished 14-3-3ε-induced cell migration and EMT. Furthermore, 14-3-3ε selectively induced Zeb-1 and Snail expression, and 14-3-3ε-induced cell migration was abrogated by Zeb-1 or Snail siRNA. In addition, the effect of 14-3-3ε-reduced E-cadherin was specifically restored by Zeb-1 siRNA. Positive 14-3-3ε expression was significantly correlated with negative E-cadherin expression, as determined by immunohistochemistry analysis in HCC tumors. Analysis of 14-3-3ε/E-cadherin expression associated with clinicopathological characteristics revealed that the combination of positive 14-3-3ε and negative E-cadherin expression is significantly correlated with higher incidence of HCC metastasis and poor 5-year overall survival. In contrast, patients with positive 14-3-3ε and positive E-cadherin expression had better prognostic outcomes than did those with negative E-cadherin expression. Significance Our findings show for the first time that E-cadherin is one of the downstream targets of 14-3-3ε in modulating HCC tumor progression. Thus, 14-3-3ε may act as an important regulator in modulating tumor metastasis by promoting EMT as well as cell migration, and it may serve as a novel prognostic biomarker or therapeutic target for HCC. PMID:23483955

Transcriptome sequencing of Eucalyptus camaldulensis seedlings subjected to water stress reveals functional single nucleotide polymorphisms and genes under selection

PubMed Central

2012-01-01

Background Water stress limits plant survival and production in many parts of the world. Identification of genes and alleles responding to water stress conditions is important in breeding plants better adapted to drought. Currently there are no studies examining the transcriptome wide gene and allelic expression patterns under water stress conditions. We used RNA sequencing (RNA-seq) to identify the candidate genes and alleles and to explore the evolutionary signatures of selection. Results We studied the effect of water stress on gene expression in Eucalyptus camaldulensis seedlings derived from three natural populations. We used reference-guided transcriptome mapping to study gene expression. Several genes showed differential expression between control and stress conditions. Gene ontology (GO) enrichment tests revealed up-regulation of 140 stress-related gene categories and down-regulation of 35 metabolic and cell wall organisation gene categories. More than 190,000 single nucleotide polymorphisms (SNPs) were detected and 2737 of these showed differential allelic expression. Allelic expression of 52% of these variants was correlated with differential gene expression. Signatures of selection patterns were studied by estimating the proportion of nonsynonymous to synonymous substitution rates (Ka/Ks). The average Ka/Ks ratio among the 13,719 genes was 0.39 indicating that most of the genes are under purifying selection. Among the positively selected genes (Ka/Ks > 1.5) apoptosis and cell death categories were enriched. Of the 287 positively selected genes, ninety genes showed differential expression and 27 SNPs from 17 positively selected genes showed differential allelic expression between treatments. Conclusions Correlation of allelic expression of several SNPs with total gene expression indicates that these variants may be the cis-acting variants or in linkage disequilibrium with such variants. Enrichment of apoptosis and cell death gene categories among the positively selected genes reveals the past selection pressures experienced by the populations used in this study. PMID:22853646

[Construction of fetal mesenchymal stem cell cDNA subtractive library].

PubMed

Yang, Li; Wang, Dong-Mei; Li, Liang; Bai, Ci-Xian; Cao, Hua; Li, Ting-Yu; Pei, Xue-Tao

2002-04-01

To identify differentially expressed genes between fetal mesenchymal stem cell (MSC) and adult MSC, especially specified genes expressed in fetal MSC, a cDNA subtractive library of fetal MSC was constructed using suppression subtractive hybridization (SSH) technique. At first, total RNA was isolated from fetal and adult MSC. Using SMART PCR synthesis method, single-strand and double-strand cDNAs were synthesized. After Rsa I digestion, fetal MSC cDNAs were divided into two groups and ligated to adaptor 1 and adaptor 2 respectively. Results showed that the amplified library contains 890 clones. Analysis of 890 clones with PCR demonstrated that 768 clones were positive. The positive rate is 86.3%. The size of inserted fragments in these positive clones was between 0.2 - 1 kb, with an average of 400 - 600 bp. SSH is a convenient and effective method for screening differentially expressed genes. The constructed cDNA subtractive library of fetal MSC cDNA lays solid foundation for screening and cloning new and specific function related genes of fetal MSC.

Expression of SLP-2 gene and CCBE1 are associated with prognosis of rectal cancer.

PubMed

Zhang, L; Liu, F-J

2017-03-01

This study aims to investigate the clinical significance of SLP-2 gene for patients with rectal cancer. To analyze the effect of CCBE1 (Collagen and calcium-binding EGF domain-containing protein 1) on rectal cancer tissue and lymph vessels of para-carcinoma tissue. A total of 50 samples of rectal cancer tissues were enrolled in the experimental group, confirmed by pathological examination. 50 samples of para-carcinoma normal tissues were collected as control group. Protein expression of SLP-2 and CCBE1 was examined with immunohistochemical staining. mRNA expression of SLP-2 was examined with RT-PCR. Lymphatic vessel density (LVD) was evaluated with LYVE-1 immunohistochemical staining. Correlation analysis was performed to assess the relationship between patient survival data and clinical pathological features of rectal cancer. Immunohistochemical staining showed that, compared with the control group, a positive expression rate of SLP-2 in the experimental group was significantly higher (68.0% vs. 24.0%, p<0.05), and mRNA of SLP-2 was also significantly increased (p<0.05). Compared with the control group, protein expression of CCBE1 in the experimental group was significantly higher (p<0.05). Moreover, the expression level of SLP-2 was remarkably associated with TNM classification and lymphatic metastasis. Further analysis demonstrated that a positive expression of CCBE1 was associated with lymphatic metastasis, LVD and Ducks classification, and had a negative correlation with survival rate. Increased expression of SLP-2 promoted the formation of lymph vessels and exacerbated lymphatic metastasis of rectal cancer via up-regulating CCBE1. As a risk factor related to lymphatic metastasis, CCBE1 could be a novel biomarker for diagnosis and prognosis of rectal cancer.

Breast cancer risk factors and HER2 over-expression in tumors.

PubMed

Swede, H; Moysich, K B; Freudenheim, J L; Quirk, J T; Muti, P C; Hurd, T C; Edge, S B; Winston, J S; Michalek, A M

2001-01-01

Few epidemiologic studies have investigated the potential role of HER2 in the etiology of breast cancer. We conducted a case-case study of 156 women with incident, invasive ductal carcinoma. Multivariate unconditional logistic regression was used to estimate the odds ratios for a HER2 positive tumor in relation to known and putative risk factors of breast cancer. HER2 status was detected by immunohistochemistry on archival tissue. HER2 positive breast cancers tended to be larger and were less likely to express estrogen receptors, and the incidence rate was higher in patients less than 40 years old. We observed an association between a self-reported history of benign breast disease and the occurrence of HER2 positive breast cancer (OR, 2.1;95% CI, 1.1-4.1). We did not detect associations between HER2 over-expression and family history of breast cancer, parity, late age at first birth, ever having breast fed an infant, or oral contraceptive use. Our findings merit consideration in light of recent evidence of HER2 amplification or over-expression in benign breast disease. Should the link to breast cancer be established, HER2 positive benign breast disease could potentially serve as an early marker for preventive intervention.

Influence of transvaginal ultrasound-guided follicular punctures in the mare on heart rate, respiratory rate, facial expression changes, and salivary cortisol as pain scoring.

PubMed

Diego, Rodrigo; Douet, Cécile; Reigner, Fabrice; Blard, Thierry; Cognié, Juliette; Deleuze, Stefan; Goudet, Ghylène

2016-10-15

Transvaginal ultrasound-guided follicular punctures are widely used in the mare for diagnosis, research, and commercial applications. The objective of our study was to determine their influence on pain, stress, and well-being in the mare, by evaluating heart rate, breath rate, facial expression changes, and salivary cortisol before, during, and after puncture. For this experiment, 21 pony mares were used. Transvaginal ultrasound-guided aspirations were performed on 11 mares. After injections for sedation, analgesia, and antispasmodia, the follicles from both ovaries were aspirated with a needle introduced through the vagina wall into the ovary. In the control group, 10 mares underwent similar treatments and injections, but no follicular aspiration. Along the session, heart rate and breath rate were evaluated by a trained veterinarian, ears position, eyelid closure, and contraction of facial muscles were evaluated, and salivary samples were taken for evaluation of cortisol concentration. A significant relaxation was observed after sedative injection in the punctured and control mares, according to ear position, eyelid closure, and contraction of facial muscles, but no difference between punctured and control animals was recorded. No significant modification of salivary cortisol concentration during puncture and no difference between punctured and control mares at any time were observed. No significant modification of the breath rate was observed along the procedure for the punctured and the control mares. Heart rate increased significantly but transiently when the needle was introduced in the ovary and was significantly higher at that time for the punctured mares than that for control mares. None of the other investigated parameters were affected at that time, suggesting discomfort is minimal and transient. Improving analgesia, e.g., through a multimodal approach, during that possibly more sensitive step could be recommended. The evaluation of facial expression changes and heart rate is easy-to-use and accurate tools to evaluate pain and well-being of the mare. Copyright © 2016 Elsevier Inc. All rights reserved.

[Effect of Tribulus terrestris extract on melanocyte-stimulating hormone expression in mouse hair follicles].

PubMed

Yang, Liu; Lu, Jian-wei; An, Jing; Jiang, Xuan

2006-12-01

To observe the effect of Tribulus terrestris extract on melanocyte stimulating hormone (MSH) expression in C57BL/6J mouse hair follicles, and investigate the role of Tribulus terrestris extract in activation, proliferation, epidermal migration of dormant hair follicle melanocytes. The aqueous extract of Tribulus terrestris was administered orally in specific pathogen-free C57BL/6J mouse at the daily dose equivalent to 1 g/1 kg in adult human, and the expression and distribution of MSH in the mouse hair follicles was observed with immunohistochemistry. The positivity rate of MSH expression in the hair follicle melanocytes was 75% in mice treated with the extract, significantly higher than the rate of only 18.75% in the control group (P<0.01). The aqueous extract of Tribulus terrestris can significantly increase MSH expression in the hair follicle melanocytes by activating tyrosinase activity and promoting melanocyte proliferation, melanine synthesis, and epidermal migration of dormant melanocytes.

Immunohistochemical analysis of PTEN, HER2/neu, and ki67 expression in patients with gastric cancer and their association with survival.

PubMed

Badary, Dalia M; Abdel-Wanis, Mostafa E; Hafez, Mohamed Z; Aboulhagag, Noha A

2017-06-01

Considering the poor prognosis of patients with gastric cancer, molecular diagnostic and prognostic markers for this cancer should be established. The aims of our study were to assess the correlations between PTEN, HER2/neu, and Ki67 expressions and clinicopathological factors of gastric cancer patients in upper Egypt, as well as their influence on OS and DFS. In this descriptive-analytic study, 42 patients with gastric carcinoma treated by postioerative chemoradiation between 2004 and 2014. Pathological review was done. Immunohistochemical staining and evaluation were performed. All the studied markers were significantly correlated with increased TNM stage. Her2/neu overexpression and positive Ki67 expression were significantly associated with histological grade. High percentage of positive Her2/neu and Ki67expression was found in gastric carcinoma tissue samples which lack PTEN expression. The one-year OS rate for the entire group (n=42) was 77.4%, whereas the DFS rate was 45%. Pathological T stage PTEN status significantly affected both OS (p=0.029 and 0.027 respectively) and DFS (p=0.006 and 0.012 respectively) rates. Multivariate Cox analyses showed that only pathological T stage was an independent prognostic factor affecting OS (P=0. 007, HR: 2.02; 95% CI: 1.2-3.38)and DFS(P<0.0001, HR: 2.69; 95% CI: 1.54-4.69). All the studied molecular markers, was significantly correlated with pathological T stage that significantly affected both OS and DFS rates. These findings indicate that these markers have an important role in gastric cancer growth and dissemination so these markers can be used as a prognostic biomarker. In addition, therapies targeting Her2 and PTEN may help develop novel therapeutics for gastric cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

ASTHMA, CHRONIC BRONCHITIS AND EMPHYSEMA—The Use of Intermittent Positive Pressure Breathing with Inspiratory Flow Rate Control: A Review of the Literature

PubMed Central

Sheldon, Gerard P.

1963-01-01

In chronic obstructive lung disease (asthma, chronic bronchitis, obstructive emphysema) there is a segmental reduction in the caliber of the airways, which always results in obstruction to air-flow. Increased airway resistance is a physiological expression of airway obstruction. The addition of inspiratory flow rate control to an intermittent positive pressure breathing device permits slow filling of a lung with obstructed airways, and is presented as a simple means of reducing the high pulmonary flow resistance and increasing the tidal volume. ImagesFigure 1. PMID:13977070

Performance Feedback Processing Is Positively Biased As Predicted by Attribution Theory.

PubMed

Korn, Christoph W; Rosenblau, Gabriela; Rodriguez Buritica, Julia M; Heekeren, Hauke R

2016-01-01

A considerable literature on attribution theory has shown that healthy individuals exhibit a positivity bias when inferring the causes of evaluative feedback on their performance. They tend to attribute positive feedback internally (e.g., to their own abilities) but negative feedback externally (e.g., to environmental factors). However, all empirical demonstrations of this bias suffer from at least one of the three following drawbacks: First, participants directly judge explicit causes for their performance. Second, participants have to imagine events instead of experiencing them. Third, participants assess their performance only after receiving feedback and thus differences in baseline assessments cannot be excluded. It is therefore unclear whether the classically reported positivity bias generalizes to setups without these drawbacks. Here, we aimed at establishing the relevance of attributions for decision-making by showing an attribution-related positivity bias in a decision-making task. We developed a novel task, which allowed us to test how participants changed their evaluations in response to positive and negative feedback about performance. Specifically, we used videos of actors expressing different facial emotional expressions. Participants were first asked to evaluate the actors' credibility in expressing a particular emotion. After this initial rating, participants performed an emotion recognition task and did--or did not--receive feedback on their veridical performance. Finally, participants re-rated the actors' credibility, which provided a measure of how they changed their evaluations after feedback. Attribution theory predicts that participants change their evaluations of the actors' credibility toward the positive after receiving positive performance feedback and toward the negative after negative performance feedback. Our results were in line with this prediction. A control condition without feedback showed that correct or incorrect performance alone could not explain the observed positivity bias. Furthermore, participants' behavior in our task was linked to the most widely used measure of attribution style. In sum, our findings suggest that positive and negative performance feedback influences the evaluation of task-related stimuli, as predicted by attribution theory. Therefore, our study points to the relevance of attribution theory for feedback processing in decision-making and provides a novel outlook for decision-making biases.

Performance Feedback Processing Is Positively Biased As Predicted by Attribution Theory

PubMed Central

Rodriguez Buritica, Julia M.; Heekeren, Hauke R.

2016-01-01

A considerable literature on attribution theory has shown that healthy individuals exhibit a positivity bias when inferring the causes of evaluative feedback on their performance. They tend to attribute positive feedback internally (e.g., to their own abilities) but negative feedback externally (e.g., to environmental factors). However, all empirical demonstrations of this bias suffer from at least one of the three following drawbacks: First, participants directly judge explicit causes for their performance. Second, participants have to imagine events instead of experiencing them. Third, participants assess their performance only after receiving feedback and thus differences in baseline assessments cannot be excluded. It is therefore unclear whether the classically reported positivity bias generalizes to setups without these drawbacks. Here, we aimed at establishing the relevance of attributions for decision-making by showing an attribution-related positivity bias in a decision-making task. We developed a novel task, which allowed us to test how participants changed their evaluations in response to positive and negative feedback about performance. Specifically, we used videos of actors expressing different facial emotional expressions. Participants were first asked to evaluate the actors’ credibility in expressing a particular emotion. After this initial rating, participants performed an emotion recognition task and did—or did not—receive feedback on their veridical performance. Finally, participants re-rated the actors’ credibility, which provided a measure of how they changed their evaluations after feedback. Attribution theory predicts that participants change their evaluations of the actors’ credibility toward the positive after receiving positive performance feedback and toward the negative after negative performance feedback. Our results were in line with this prediction. A control condition without feedback showed that correct or incorrect performance alone could not explain the observed positivity bias. Furthermore, participants’ behavior in our task was linked to the most widely used measure of attribution style. In sum, our findings suggest that positive and negative performance feedback influences the evaluation of task-related stimuli, as predicted by attribution theory. Therefore, our study points to the relevance of attribution theory for feedback processing in decision-making and provides a novel outlook for decision-making biases. PMID:26849646

Strong positive selection and recombination drive the antigenic variation of the PilE protein of the human pathogen Neisseria meningitidis.

PubMed

Andrews, T Daniel; Gojobori, Takashi

2004-01-01

The PilE protein is the major component of the Neisseria meningitidis pilus, which is encoded by the pilE/pilS locus that includes an expressed gene and eight homologous silent fragments. The silent gene fragments have been shown to recombine through gene conversion with the expressed gene and thereby provide a means by which novel antigenic variants of the PilE protein can be generated. We have analyzed the evolutionary rate of the pilE gene using the nucleotide sequence of two complete pilE/pilS loci. The very high rate of evolution displayed by the PilE protein appears driven by both recombination and positive selection. Within the semivariable region of the pilE and pilS genes, recombination appears to occur within multiple small sequence blocks that lie between conserved sequence elements. Within the hypervariable region, positive selection was identified from comparison of the silent and expressed genes. The unusual gene conversion mechanism that operates at the pilE/pilS locus is a strategy employed by N. meningitidis to enhance mutation of certain regions of the PilE protein. The silent copies of the gene effectively allow "parallelized" evolution of pilE, thus enabling the encoded protein to rapidly explore a large area of sequence space in an effort to find novel antigenic variants.

Immunohistochemical Assessment of HER3 Expression in Odontogenic Cysts.

PubMed

Honarmand, Marieh; Saravani, Shirin; Kamyab, Nazanin; Jahantigh, Mehdi; Torabi Parizi, Molouk

2015-11-01

It has been demonstrated that HER3 plays an important role in some human cancers and the HER3 expression is associated with worse survival in solid tumors. This study was conducted to compare HER3 expression in epithelial lining of radicular cysts (RCs), dentigerous cysts (DCs) and odontogenic keratocysts (OKCs). This was a descriptive-analytical study, which assessed all 57 paraffin blocks of RCs, DCs and OKCs (21 RCs, 16 DCs, 20 OKC) from pathological archive of Dentistry College of Zahedan, Iran. The HER3 expression in cytoplasm and membrane was examined by immunohistochemical method. The data collected was analyzed using SPSS16 by ANOVA and Chi-square. P < 0.05 was considered as statistically significant. The HER3 expression had positive results in 52.4% of OKC, 50% of DC and only 20% of RC samples. There was a significant difference between HER3 expression in OKCs and RCs. The HER3 expression in developmental odontogenic cysts was higher than that in inflammatory odontogenic cysts. The higher rate of HER3 expression in OKC may justify inherent growth potential, stimulation-independent proliferation capability, invasive growth and high recurrence rate of the cyst accepted today as a tumor.

Prognostic impact of programmed cell death 1 ligand 1 expression in human leukocyte antigen class I-positive hepatocellular carcinoma after curative hepatectomy.

PubMed

Umemoto, Yuichiroh; Okano, Shinji; Matsumoto, Yoshihiro; Nakagawara, Hidekazu; Matono, Rumi; Yoshiya, Shohei; Yamashita, Yo-Ichi; Yoshizumi, Tomoharu; Ikegami, Toru; Soejima, Yuji; Harada, Mamoru; Aishima, Shinichi; Oda, Yoshinao; Shirabe, Ken; Maehara, Yoshihiko

2015-01-01

Hepatocellular carcinoma (HCC) is one of the most common solid tumors worldwide. Surgery is potentially curative, but high recurrence rates worsen patient prognosis. The interaction between the proteins programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) is an important immune checkpoint. The significance of PD-L1 expression and human leukocyte antigen class I (HLA class I), recognized by CD8 T cells, in the prognosis of patients with HCC remains to be determined. We assessed the levels of PD-L1 and HLA class I expression on HCC samples from 80 patients who had undergone hepatectomy at our institution, and evaluated the correlations between PD-L1 and HLA class I expression and patient prognosis. High HLA class I expression was correlated with significantly better recurrence-free survival (RFS), but not overall survival (OS). Multivariate analysis showed that high HLA class I expression was an independent predictor of improved RFS. Low expression of PD-L1 on HCC tended to predict better OS, but the difference was not statistically significant. PD-L1 expression on HCC correlated with the number of CD163-positive macrophages and HLA class I expression with CD3-positive cell infiltration. Univariable and multivariable analyses showed that combined PD-L1 low/HLA class I high expression on HCCs was prognostic for improved OS and RFS. PD-L1 status may be a good predictor of prognosis in HCC patients with high HLA class I expression. Novel therapies targeting the PD-L1/PD-1 pathway may improve the prognosis of patients with HCC.

Somatostatin Receptor SSTR-2a Expression Is a Stronger Predictor for Survival Than Ki-67 in Pancreatic Neuroendocrine Tumors

PubMed Central

Mehta, Shreya; de Reuver, Philip R.; Gill, Preetjote; Andrici, Juliana; D’Urso, Lisa; Mittal, Anubhav; Pavlakis, Nick; Clarke, Stephen; Samra, Jaswinder S.; Gill, Anthony J.

2015-01-01

Abstract Somatostatin receptors (SSTR) are commonly expressed by neuroendocrine tumors. Expression of SSTR-2a and SSTR-5 may impact symptomatic management; however, the impact on survival is unclear. The aim of this study is to correlate SSTR-2a and SSTR-5 expression in pancreatic neuroendocrine tumors (PNETs) with survival. This study is designed to determine the prognostic significance of somatostatin receptors SSTR-2a and SSTR-5 in PNETs. This retrospective cohort study included cases of resected PNETs between 1992 and 2014. Clinical data, histopathology, expression of SSTR and Ki-67 by immunohistochemistry, and long-term survival were analyzed. A total of 99 cases were included in this study. The mean age was 57.8 years (18–87 years) and median tumor size was 25 mm (range 8–160 mm). SSTR-2a and SSTR-5 expression was scored as negative (n = 19, 19.2%; n = 75, 75.8%, respectively) and positive (n = 80, 80.1%; n = 24, 24.2%). The median follow-up was 49 months. SSTR-2a expression was associated with improved overall survival, with cumulative survival rates at 1, 3, and 5 years being 97.5%, 91.5%, and 82.9%, respectively. Univariate analysis demonstrated better survival in SSTR-2a positive patients (log rank P = 0.04). SSTR-5 expression was not associated with survival outcomes (log rank P = 0.94). Multivariate analysis showed that positive SSTR-2a expression is a stronger prognostic indicator for overall survival [Hazard Ratio (HR): 0.2, 95% Confidence interval (CI): 0.1–0.8] compared to high Ki-67 (HR: 0.8, 95% CI: 0.1–5.7). Expression of SSTR-2a is an independent positive prognostic factor for survival in PNETs. PMID:26447992

A clinicopathological study of the expression of extracellular matrix components in urothelial carcinoma.

PubMed

Ioachim, Elli; Michael, Michalis; Stavropoulos, Nicolaos E; Kitsiou, Evangelia; Salmas, Marios; Malamou-Mitsi, Vasiliki

2005-03-01

To measure the immunohistochemical expression of the extracellular matrix (ECM) components tenascin, fibronectin, collagen type IV and laminin in urothelial carcinomas, and to correlate their expression with clinicopathological features to clarify the prognostic value of these molecules and their role in tumour progression. Tumour specimens obtained during transurethral resection of bladder tumour (TURBT) from 103 patients (82 men and 2 1 women, mean age 66.7 years, range 27-89) were studied retrospectively. The expression of tenascin, fibronectin, collagen type IV and laminin was correlated with clinicopathological features (tumour grade and stage, multiplicity, simultaneous in situ component, the proliferative activity as estimated by the two proliferation associated indices, Ki-67 and proliferating cell nuclear antigen, the recurrence rate, and the progression of invading tumour). Specimens investigated for tenascin expression from patients with superficial bladder cancers were categorized into 28 treated by TURBT only and 53 who had TURBT followed by intravesical instillations of interferon. Cytoplasmic tenascin expression was detected in tumour cells in 20% of specimens. Tenascin was expressed in the tumour stroma in 76% of specimens, and was positively correlated with tumour grade and stage. Stromal tenascin expression was positively correlated with proliferative activity, and with the expression of fibronectin and collagen type IV. Fibronectin was expressed in the tumour stroma in 89% of specimens and was positively correlated with tumour stage, proliferative activity, and expression of collagen type IV and laminin. Collagen type IV was expressed in 93% of specimens, and was positively correlated with tumour grade and stage. Laminin was expressed in 78% of specimens and had no significant correlation with the clinicopathological features. Patients treated with TURBT alone and who had low levels of tenascin had a longer tumour-free interval than those with high levels of tenascin. Levels of tenascin might be valuable for predicting the risk of early recurrence. The expression of tenascin, fibronectin and collagen type IV seems to be correlated with more aggressive tumour behaviour. Furthermore, their interrelationships could indicate that they are involved in the remodelling of bladder cancer tissue, probably influencing tumour progression.

Something to sink your teeth into: The presence of teeth augments ERPs to mouth expressions.

PubMed

daSilva, Elizabeth B; Crager, Kirsten; Geisler, Danika; Newbern, Powell; Orem, Benjamin; Puce, Aina

2016-02-15

If the whites of the sclera can impact neural processing of eye expressions (Hardee, Thompson, & Puce, 2008; Whalen et al., 1998), do seen teeth affect neural responses to mouth expressions? Twenty participants (10 females; ages 22-31) viewed avatar mouth images depicting grimaces, smiles and open mouth expressions that were presented with and without teeth. A continuous 256 channel electroencephalogram (EEG) was recorded while subjects completed two tasks: an implicit task evaluating stimulus color and an explicit task evaluating mouth expression valence. Event related potential (ERP) peak amplitudes and latencies and area under the curve (AUC) were measured in individual subject averaged ERPs. Statistical testing revealed a main effect of the presence of Teeth for P100, N170, and vertex positive potential (VPP) amplitudes and for slow positive wave (SPW) AUC. Task by teeth interactions occurred for P250 amplitude, underscoring how explicit task demands can influence neural processing. Arousal ratings co-varied with teeth presence, suggesting that low-level visual features such as teeth may drive the saliency of emotional expressions, and lie at the core of differences in neural processing to different emotional expressions. Copyright © 2015 Elsevier Inc. All rights reserved.

Association between EML4-ALK fusion gene and thymidylate synthase mRNA expression in non-small cell lung cancer tissues

PubMed Central

XU, CHUN-WEI; WANG, GANG; WANG, WU-LONG; GAO, WEN-BIN; HAN, CHUAN-JUN; GAO, JING-SHAN; ZHANG, LI-YING; LI, YANG; WANG, LIN; ZHANG, YU-PING; TIAN, YU-WANG; QI, DONG-DONG

2015-01-01

This study aimed to investigate the association of the mRNA expression of the echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene with that of thymidylate synthase (TYMS) in non-small cell lung cancer (NSCLC) tissues. Quantitative polymerase chain reaction was used to detect the expression of EML4-ALK fusion gene and TYMS mRNA in 257 cases of NSCLC. The positive rate of EML4-ALK fusion gene was 4.28% in the NSCLC tissues (11/257), and was higher in nonsmokers than in smokers (P<0.05); TYMS mRNA expression was detected in 63.42% (163/257) of cases. An association of the EML4-ALK fusion gene with TYMS expression was detected; a low expression level of TYMS mRNA was observed more frequently when the EML4-ALK fusion gene was present than when it was not detected (P<0.05). In conclusion, patients positive for the EML4-ALK fusion gene in NSCLC tissues are likely to have a low expression level of TYMS, and may benefit from the first-line chemotherapy drug pemetrexed. PMID:26136951

Association between EML4-ALK fusion gene and thymidylate synthase mRNA expression in non-small cell lung cancer tissues.

PubMed

Xu, Chun-Wei; Wang, Gang; Wang, Wu-Long; Gao, Wen-Bin; Han, Chuan-Jun; Gao, Jing-Shan; Zhang, Li-Ying; Li, Yang; Wang, Lin; Zhang, Yu-Ping; Tian, Yu-Wang; Qi, Dong-Dong

2015-06-01

This study aimed to investigate the association of the mRNA expression of the echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene with that of thymidylate synthase (TYMS) in non-small cell lung cancer (NSCLC) tissues. Quantitative polymerase chain reaction was used to detect the expression of EML4-ALK fusion gene and TYMS mRNA in 257 cases of NSCLC. The positive rate of EML4-ALK fusion gene was 4.28% in the NSCLC tissues (11/257), and was higher in nonsmokers than in smokers (P<0.05); TYMS mRNA expression was detected in 63.42% (163/257) of cases. An association of the EML4-ALK fusion gene with TYMS expression was detected; a low expression level of TYMS mRNA was observed more frequently when the EML4-ALK fusion gene was present than when it was not detected (P<0.05). In conclusion, patients positive for the EML4-ALK fusion gene in NSCLC tissues are likely to have a low expression level of TYMS, and may benefit from the first-line chemotherapy drug pemetrexed.

Autistic and schizotypal traits and global functioning in bipolar I disorder.

PubMed

Abu-Akel, Ahmad; Clark, Jennifer; Perry, Amy; Wood, Stephen J; Forty, Liz; Craddock, Nick; Jones, Ian; Gordon-Smith, Katherine; Jones, Lisa

2017-01-01

To determine the expression of autistic and positive schizotypal traits in a large sample of adults with bipolar I disorder (BD I), and the effect of co-occurring autistic and positive schizotypal traits on global functioning in BD I. Autistic and positive schizotypal traits were self-assessed in 797 individuals with BD-I recruited by the Bipolar Disorder Research Network. Differences in global functioning (rated using the Global Assessment Scale) during lifetime worst depressive and manic episodes (GASD and GASM respectively) were calculated in groups with high/low autistic and positive schizotypal traits. Regression analyses assessed the interactive effect of autistic and positive schizotypal traits on global functioning. 47.2% (CI=43.7-50.7%) showed clinically significant levels of autistic traits, and 23.22% (95% CI=20.29-26.14) showed clinically significant levels of positive schizotypal traits. In the worst episode of mania, the high autistic, high positive schizotypal group had better global functioning compared to the other groups. Individual differences analyses showed that high levels of both traits were associated with better global functioning in both mood states. Autistic and schizotypal traits were assessed using self-rated questionnaires. Expression of autistic and schizotypal traits in adults with BD I is prevalent, and may be important to predict illness aetiology, prognosis, and diagnostic practices in this population. Future work should focus on replicating these findings in independent samples, and on the biological and/or psychosocial mechanisms underlying better global functioning in those who have high levels of both autistic and positive schizotypal traits. Copyright © 2016 Elsevier B.V. All rights reserved.

Significance of hepatitis B virus surface antigen, hepatitis C virus expression in hepatocellular carcinoma and pericarcinomatous tissues

PubMed Central

Xuan, Shi-Ying; Xin, Yong-Ning; Chen, Hua; Shi, Guang-Jun; Guan, Hua-Shi; Li, Yang

2007-01-01

AIM: To investigate the correlation between hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV) expression in hepatocellular carcinoma (HCC), the HAI score of the noncancerous region of the liver and the serum Alpha fetoprotein (AFP) level. METHODS: The patterns of HBsAg and HCV in 100 cases of HCC and their surrounding liver tissues were studied on paraffin-embedded sections with immuno-histochemistry, the histological status was determined by one pathologist and one surgeon simultaneously using the hepatitis activity index (HAI) score, and AFP was detected by radioimmunity. The study included 100 consecutive patients who underwent curative resection for HCC. Based on HBsAg and HCV expression, the patients were classified into 4 groups: patients positive for HBsAg (HBsAg group), patients positive for HCV (HCV group), patients negative for both HCV and HBsAg (NBNC group) and patients positive for both HBsAg and HCV (BC group). RESULTS: The BC group had significantly higher HAI scores than the other three groups. (BC > HCV > HBsAg > NBNC). HBV and HCV virus infection was positively correlated with HAI (rs = 0.39, P = 0.0001). The positive rate of AFP (85.7%) and the value of AFP (541.2 ng/mL) in the group with HBV and HCV co-infection were the highest among the four groups. The positive rate (53.3%) of AFP and the value of AFP ( 53.3 ng/mL) in the group with none-infection of HBV and HCV were the lowest. HBV and HCV virus infection was positively correlated with AFP(rs = 0.38, P = 0.0001). CONCLUSION: The AFP increase in patients with liver cancer was positively correlated with the infection of HBV and HCV. The serum AFP elevation by the infection of HBV and HCV is one of mechanisms which lead to hepatocarcinogenesis, and the antivirus intervening treatment of hepatitis is significant for the prognosis of liver cancer. From our Spearman’s rank correlation analysis, we can conclude that the severity of virally induced inflammation is correlated with HBsAg and HCV expression in HCC tissues and noncancerous tissues. Prior co-infection of HBV in HCV patients may be an adverse risk factor for intrahepatic inflammation. PMID:17465484

Lacking prognostic significance of beta 2-microglobulin, MHC class I and class II antigen expression in breast carcinomas.

PubMed Central

Wintzer, H. O.; Benzing, M.; von Kleist, S.

1990-01-01

To evaluate the impact of MHC antigen expression on the survival of patients with cancer, 77 human breast carcinomas were investigated for the expression of beta 2-microglobulin (beta 2m), HLA-A,B,C and HLA-DR. Thirty-one benign breast tumours were stained for comparison. The results for the carcinomas were related to the survival data of the cancer patients. The expression of beta 2m, HLA-A,B,C and HLA-DR was significantly lower in malignant tumours compared to the benign lesions. Whereas all benign tumours were positive for beta 2m and HLA-A,B,C and 28/31 positive for HLA-DR the following positivity rates were found in carcinomas: 74/77 for beta 2m, 57/77 for HLA-A,B,C and 10/77 for HLA-DR. The follow-up (median 45 months) of 66 cancer patients for overall survival and of 65 patients for disease-free survival revealed no influence of beta 2m, HLA-A,B,C or HLA-DR expression on the prognosis of this cancer. In conclusion, experimental data indicating the importance of MHC antigens in anti-tumour responses are not confirmed by the analysis of cancer patient survival data. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:2201398

Gene expression profiling of histologically normal breast tissue in females with human epidermal growth factor receptor 2‑positive breast cancer.

PubMed

Zubor, Pavol; Hatok, Jozef; Moricova, Petra; Kapustova, Ivana; Kajo, Karol; Mendelova, Andrea; Sivonova, Monika Kmetova; Danko, Jan

2015-02-01

Gene expression profile‑based taxonomy of breast cancer (BC) has been described as a significant breakthrough in comprehending the differences in the origin and behavior of cancer to allow individually tailored therapeutic approaches. In line with this, we hypothesized that the gene expression profile of histologically normal epithelium (HNEpi) could harbor certain genetic abnormalities predisposing breast tissue cells to develop human epidermal growth factor receptor 2 (HER2)‑positive BC. Thus, the aim of the present study was to assess gene expression in normal and BC tissue (BCTis) from patients with BC in order to establish its value as a potential diagnostic marker for cancer development. An array study evaluating a panel of 84 pathway‑ and disease‑specific genes in HER2‑positive BC and tumor‑adjacent HNEpi was performed using quantitative polymerase chain reaction in 12 patients using microdissected samples from frozen tissue. Common prognostic and predictive parameters of BC were assessed by immunohistochemistry and in situ hybridization. In the BCTis and HNEpi samples of 12 HER2‑positive subjects with BC, the expression of 2,016 genes was assessed. A total of 39.3% of genes were deregulated at a minimal two‑fold deregulation rate and 10.7% at a five‑fold deregulation rate in samples of HNEpi or BCTis. Significant differences in gene expression between BCTis and HNEpi samples were revealed for BCL2L2, CD44, CTSD, EGFR, ERBB2, ITGA6, NGFB, RPL27, SCBG2A1 and SCGB1D2 genes (P<0.05), as well as GSN, KIT, KLK5, SERPINB5 and STC2 genes (P<0.01). Insignificant differences (P<0.07) were observed for CCNA1, CLU, DLC1, GABRP and IL6 genes. The ontological gene analyses revealed that the majority of the deregulated genes in the HNEpi samples were part of the functional gene group directly associated with BC origin and prognosis. Functional analysis showed that the most frequent gene deregulations occurred in genes associated with apoptosis and cell cycle regulation in BCTis samples, and with angiogenesis, regulation of the cell cycle and transcriptional activity in HNEpi samples. The molecular profiling of HNEpi breast tissue revealed gene expression abnormalities that may represent potential markers of increased risk for HER2‑positive malignant transformation of breast tissue, and may be able to be employed as predictors of prognosis.

CD44v3 and VEGF-C expression and its relationship with lymph node metastasis in squamous cell carcinomas of the uterine cervix.

PubMed

Liu, Ye-Qing; Li, Hai-Feng; Han, Jing-Jing; Tang, Qiong-Lan; Sun, Qing; Huang, Zhi-Quan; Li, Hai-Gang

2014-01-01

To investigate the expression of CD44v3 and vascular endothelial growth factor-C (VEGF-C) and their relationship with lymph node metastasis in squamous cell carcinomas (SCC) of the uterine cervix. Expression of CD44v3 and VEGF-C was analyzed in 109 cases of cervical SCC by immunohistochemistry (IHC). The relationship was analyzed between expression and the patient age, histological differentiation, formation of tumor emboli in lymphoid vessels, lymph node metastasis, FIGO staging, and TNM classification. Expression rates for both CD44v3 and VEGF-C were 43.1% in cervical SCC. The cells with positive immunohistochemical staining of CD44v3 were distributed mainly around the keratin pearls in well differentiated carcinomas, but distributed diffusely in the moderately and poorly differentiated lesions. VEGF-C was found stained positively in most of the tumor cells. There were differences in expression between normal epithelium and atypical hyperplasia as well as carcinoma. Both CD44v3 and VEGF-C were found to be associated positively with lymph node metastasis and TNM classification (both p=0.000). Neither CD44v3 nor VEGF-C was found to be associated with patient age, histological differentiation, formation of tumor emboli in lymphoid vessels and FIGO staging. CD44v3 was found to be associated with VEGF-C positively (p=0.000). Abnormal expression of CD44v3 and VEGF-C is associated closely with the lymph node metastasis in cervical SCC, and these agents may cooperate in carcinogenesis and development of metastatic lesions.

Infrequent Immunohistochemical Expression of Napsin A in Endometrial Carcinomas.

PubMed

Al-Maghrabi, Jaudah A; Butt, Nadeem S; Anfinan, Nisrin; Sait, Khalid; Sait, Hesham; Marzouki, Anas; Khabaz, Mohamad Nidal

2017-10-01

Many studies described napsin A as a specific diagnostic marker that aids in differentiating lung adenocarcinomas from other respiratory tumors. This study describes the expression phenotype of napsin A in endometrial neoplasms, it investigates the relationship between this expression profile and the clinicopathologic parameters, and assess its utilization as an independent predictive marker. A total of 76 cases of previously diagnosed endometrial carcinoma (including 53 endometrioid adenocarcinomas, 6 endometrioid adenocarcinomas with squamous differentiation, 9 serous adenocarcinomas, 6 clear cell adenocarcinomas, and 2 malignant mixed mullerian tumors) and 30 tissue samples of noncancerous endometrium (including 16 proliferative endometriums, 10 secretory endometriums and 4 endometrial polyps) were retrieved from the archives of Pathology Department at King Abdulaziz University, Jeddah, Saudi Arabia. For napsin A detection, tissue microarrays and immunostaining were used. A total number of 12 (15.78%) cases were positive for napsin A immunostaining. Brown granular cytoplasmic expression of napsin A was detected in 9.4% of endometrioid adenocarcinomas, 16.7% of endometrioid adenocarcinomas with squamous differentiation, 22.2% of papillary serous endometrial carcinomas, and 66.7% of clear cell carcinomas. Three (10%) control cases showed similar granular cytoplasmic expression. Positive napsin A immunostaining was more frequent in clear cell carcinoma, and there is a significant association between positive napsin A immunostaining and clear cell carcinoma (P-value=0.007). Significant associations have been found also between napsin A expression and older ages (above 60 y) and higher stage (IVB), the P-values of which were 0.035 and 0.043, respectively, but not with the tumor recurrence or survival rate. Although napsin A is infrequently expressed in endometrial carcinomas, positive results of napsin A immunostaining in endometrial neoplasms might support the diagnosis of clear cell carcinoma when the pathologic differential diagnosis includes other histologic subtypes.

Biological Differences between Hanwoo longissimus dorsi and semimembranosus Muscles in Collagen Synthesis of Fibroblasts.

PubMed

Subramaniyan, Sivakumar Allur; Hwang, Inho

2017-01-01

Variations in physical toughness between muscles and animals are a function of growth rate and extend of collagen type I and III. The current study was designed to investigate the ability of growth rate, collagen concentration, collagen synthesizing and degrading genes on two different fibroblast cells derived from Hanwoo m. longissimus dorsi (LD) and semimembranosus (SM) muscles. Fibroblast cell survival time was determined for understanding about the characteristics of proliferation rate between the two fibroblasts. We examined the collagen concentration and protein expression of collagen type I and III between the two fibroblasts. The mRNA expression of collagen synthesis and collagen degrading genes to elucidate the molecular mechanisms on toughness and tenderness through collagen production between the two fibroblast cells. From our results the growth rate, collagen content and protein expression of collagen type I and III were significantly higher in SM than LD muscle fibroblast. The mRNA expressions of collagen synthesized genes were increased whereas the collagen degrading genes were decreased in SM than LD muscle. Results from confocal microscopical investigation showed increased fluorescence of collagen type I and III appearing stronger in SM than LD muscle fibroblast. These results implied that the locomotion muscle had higher fibroblast growth rate, leads to produce more collagen, and cause tougher than positional muscle. This in vitro study mirrored that background toughness of various muscles in live animal is likely associated with fibroblast growth pattern, collagen synthesis and its gene expression.

Research on channel characteristics of differential multi pulse position modulation without background noise

NASA Astrophysics Data System (ADS)

Gao, Zhuo; Zhan, Weida; Sun, Quan; Hao, Ziqiang

2018-04-01

Differential multi-pulse position modulation (DMPPM) is a new type of modulation technology. There is a fast transmission rate, high bandwidth utilization, high modulation rate characteristics. The study of DMPPM modulation has important scientific value and practical significance. Channel capacity is one of the important indexes to measure the communication capability of communication system, and studying the channel capacity of DMPPM without background noise is the key to analyze the characteristics of DMPPM. The DMPPM theoretical model is established. The symbol structure of DMPPM with guard time slot is analyzed, and the channel capacity expression of DMPPM is deduced. Simulation analysis by MATLAB. The curves of unit channel capacity and capacity efficiency at different pulse and photon counting rates are analyzed. The results show that DMPPM is more advantageous than multi-pulse position modulation (MPPM), and is more suitable for future wireless optical communication system.

Apoptosis in response to heat stress is positively associated with heat-shock protein 90 expression in chicken myocardial cells in vitro.

PubMed

Zhang, Xiao-Hui; Wu, Hong; Tang, Shu; Li, Qiao-Ning; Xu, Jiao; Zhang, Miao; Su, Ya-Nan; Yin, Bin; Zhao, Qi-Ling; Kemper, Nicole; Hartung, Joerg; Bao, En-Dong

2017-06-30

To determine heat-shock protein (Hsp)90 expression is connected with cellular apoptotic response to heat stress and its mechanism, chicken ( Gallus gallus ) primary myocardial cells were treated with the Hsp90 promoter, aspirin, and its inhibitor, geldanamycin (GA), before heat stress. Cellular viability, heat-stressed apoptosis and reactive oxygen species level under different treatments were measured, and the expression of key proteins of the signaling pathway related to Hsp90 and their colocalization with Hsp90 were detected. The results showed that aspirin treatment increased the expression of protein kinase B (Akt), the signal transducer and activator of transcription (STAT)-3 and p-IKKα/β and the colocalization of Akt and STAT-3 with Hsp90 during heat stress, which was accompanied by improved viability and low apoptosis. GA significantly inhibited Akt expression and p-IKKα/β level, but not STAT-3 quantity, while the colocalization of Akt and STAT-3 with Hsp90 was weakened, followed by lower cell viability and higher apoptosis. Aspirin after GA treatment partially improved the stress response and apoptosis rate of tested cells caused by the recovery of Akt expression and colocalization, rather than the level of STAT-3 (including its co-localization with Hsp90) and p-IKKα/β. Therefore, Hsp90 expression has a positive effect on cellular capacity to resist heat-stressed injury and apoptosis. Moreover, inhibition of Hsp90 before stress partially attenuated its positive effects.

Golgi-Related Proteins GOLPH2 (GP73/GOLM1) and GOLPH3 (GOPP1/MIDAS) in Cutaneous Melanoma: Patterns of Expression and Prognostic Significance.

PubMed

Donizy, Piotr; Kaczorowski, Maciej; Biecek, Przemyslaw; Halon, Agnieszka; Szkudlarek, Teresa; Matkowski, Rafal

2016-10-01

GOLPH2 and GOLPH3 are Golgi-related proteins associated with aggressiveness and progression of a number of cancers. Their prognostic significance in melanoma has not yet been analyzed. We performed immunohistochemical analysis for GOLPH2 and GOLPH3 in 20 normal skin, 30 benign nevi and 100 primary melanoma tissue samples and evaluated their expression in three compartments: cancer cells, tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs). High levels of both proteins in melanoma cells were associated with characteristics of aggressive disease, and shorter disease-free survival (DFS) and cancer-specific overall survival (CSOS). On the contrary, increased numbers of GOLPH2-positive and GOLPH3-positive TAMs were observed in thinner, non-ulcerated tumors, with brisk lymphocytic reaction and absent lymphangioinvasion. Distant metastases were not observed among patients with high numbers of GOLPH2-positive TAMs. Increased expression of either protein in TAMs was related to prolonged CSOS and DFS. Similarly, GOLPH3-expressing CAFs were more frequent in thin melanomas with low mitotic rate, without ulceration and lymphangioinvasion. Moreover, increased GOLPH3-positive CAFs correlated with the absence of regional or distant metastases, and with longer CSOS and DFS. GOLPH2 expression was not observed in CAFs. Our results suggest that GOLPH2 and GOLPH3 play a role in melanoma progression and are potential targets for molecular-based therapies.

Positively Biased Processing of Mother's Emotions Predicts Children's Social and Emotional Functioning.

PubMed

Donohue, Meghan Rose; Goodman, Sherryl H; Tully, Erin C

Risk for internalizing problems and social skills deficits likely emerges in early childhood when emotion processing and social competencies are developing. Positively biased processing of social information is typical during early childhood and may be protective against poorer psychosocial outcomes. We tested the hypothesis that young children with relatively less positively biased attention to, interpretations of, and attributions for their mother's emotions would exhibit poorer prosocial skills and more internalizing problems. A sample of 4- to 6-year-old children ( N =82) observed their mothers express happiness, sadness and anger during a simulated emotional phone conversation. Children's attention to their mother when she expressed each emotion was rated from video. Immediately following the phone conversation, children were asked questions about the conversation to assess their interpretations of the intensity of mother's emotions and misattributions of personal responsibility for her emotions. Children's prosocial skills and internalizing problems were assessed using mother-report rating scales. Interpretations of mother's positive emotions as relatively less intense than her negative emotions, misattributions of personal responsibility for her negative emotions, and lack of misattributions of personal responsibility for her positive emotions were associated with poorer prosocial skills. Children who attended relatively less to mother's positive than her negative emotions had higher levels of internalizing problems. These findings suggest that children's attention to, interpretations of, and attributions for their mother's emotions may be important targets of early interventions for preventing prosocial skills deficits and internalizing problems.

Positively Biased Processing of Mother’s Emotions Predicts Children’s Social and Emotional Functioning

PubMed Central

Donohue, Meghan Rose; Goodman, Sherryl H.; Tully, Erin C.

2016-01-01

Risk for internalizing problems and social skills deficits likely emerges in early childhood when emotion processing and social competencies are developing. Positively biased processing of social information is typical during early childhood and may be protective against poorer psychosocial outcomes. We tested the hypothesis that young children with relatively less positively biased attention to, interpretations of, and attributions for their mother’s emotions would exhibit poorer prosocial skills and more internalizing problems. A sample of 4- to 6-year-old children (N=82) observed their mothers express happiness, sadness and anger during a simulated emotional phone conversation. Children’s attention to their mother when she expressed each emotion was rated from video. Immediately following the phone conversation, children were asked questions about the conversation to assess their interpretations of the intensity of mother’s emotions and misattributions of personal responsibility for her emotions. Children’s prosocial skills and internalizing problems were assessed using mother-report rating scales. Interpretations of mother’s positive emotions as relatively less intense than her negative emotions, misattributions of personal responsibility for her negative emotions, and lack of misattributions of personal responsibility for her positive emotions were associated with poorer prosocial skills. Children who attended relatively less to mother’s positive than her negative emotions had higher levels of internalizing problems. These findings suggest that children’s attention to, interpretations of, and attributions for their mother’s emotions may be important targets of early interventions for preventing prosocial skills deficits and internalizing problems. PMID:28348456

Cellulose effects on morphology and elasticity of Vibrio fischeri biofilms.

PubMed

Ziemba, Christopher; Shabtai, Yael; Piatkovsky, Maria; Herzberg, Moshe

2016-01-01

Cellulose effects on Vibrio fischeri biofilm morphology were tested for the wild-type and two of its isogenic mutants that either exhibit increased cellulose production or do not produce cellulose at all. Confocal laser scanning microscopy imaging of each biofilm revealed that total sessile volume increases with cellulose expression, but the size of colonies formed with cellulose was smaller, creating a more diffuse biofilm. These morphological differences were not attributed to variations in bacterial deposition, extracellular polymeric substances affinity to the surface or bacterial growth. A positive correlation was found between cellulose expression, Young's (elastic) modulus of the biofilm analyzed with atomic force microscope and shear modulus of the related extracellular polymeric substances layers analyzed with quartz crystal microbalance with dissipation monitoring. Cellulose production also correlated positively with concentrations of extracellular DNA. A significant negative correlation was observed between cellulose expression and rates of diffusion through the extracellular polymeric substances. The difference observed in biofilm morphology is suggested as a combined result of cellulose and likely extracellular DNA (i) increasing biofilm Young's modulus, making shear removal more difficult, and (ii) decreased diffusion rate of nutrients and wastes into and out of the biofilm, which effectively limits colony size.

Metastasis-associated gene 1 expression in human medulloblastoma and its association with invasion and metastasis in medulloblastoma Daoy cell lines.

PubMed

Chen, Y S; Li, S P; Xiao, H; Xie, Z Y; Tan, M X; Liu, B; Zhang, W M

2016-06-17

This study aims to investigate the expression of metastasis-associated gene 1 (MTA1) in human medulloblastoma, and its significance in the invasion and metastasis in a medulloblastoma cell line. Positive expression rate of MTA1 protein in medulloblastoma and adjacent normal tissues collected from 29 medulloblastoma patients was detected by immunohistochemistry assay in vivo. In in vitro experiments, Daoy cells were transfected with MTA1-targeted small interfering RNA (siRNA, MTA1-siRNA group), niRNA (MTA1-niRNA group), and plasmid vectors (control group). Transfection efficiency was evaluated by PT-PCR and western blot; cell adhesion, migration, and invasion capacity was assessed by adhesion assays, scratch assays, and transwell chamber invasion assays, respectively. Results indicated that the positive expression rate of MTA1 protein in the medulloblastoma tissues was higher as compared with that of the adjacent normal tissues (P < 0.05). In addition, mRNA and protein expression of MTA1 in the MTA1-siRNA group was lower than that in the control and MTA1- niRNA groups (P < 0.05). Adhesion, migration, and invasion capacity of Daoy cells in the MTA1-siRNA group was inhibited as compared with the control and MTA1-niRNA groups (P < 0.05). In conclusion, MTA1 expression was increased in medulloblastoma cells, while MTA1 knockdown in medulloblastoma cells inhibited MTA1 expression. In addition, MTA1 knockdown inhibited the adhesion, migration, and invasive capabilities of medulloblastoma cells. It is possible that MTA1 can serve as a biomarker and a potential therapeutic target for medulloblastoma.

Expression profile of IGF-I-calcineurin-NFATc3-dependent pathway genes in skeletal muscle during early development between duck breeds differing in growth rates.

PubMed

Shu, Jingting; Li, Huifang; Shan, Yanju; Xu, Wenjuan; Chen, Wenfeng; Song, Chi; Song, Weitao

2015-06-01

The insulin-like growth factor I (IGF-I)-calcineurin (CaN)-NFATc signaling pathways have been implicated in the regulation of myocyte hypertrophy and fiber-type specificity. In the present study, the expression of the CnAα, NFATc3, and IGF-I genes was quantified by RT-PCR for the first time in the breast muscle (BM) and leg muscle (LM) on days 13, 17, 21, 25, and 27 of embryonic development, as well as at 7 days posthatching (PH), in Gaoyou and Jinding ducks, which differ in their muscle growth rates. Consistent expression patterns of CnAα, NFATc3, and IGF-I were found in the same anatomical location at different development stages in both duck breeds, showing significant differences in an age-specific fashion. However, the three genes were differentially expressed in the two different anatomical locations (BM and LM). CnAα, NFATc3, and IGF-I messenger RNA (mRNA) could be detected as early as embryonic day 13 (ED13), and the highest level appeared at this stage in both BM and LM. Significant positive relationships were observed in the expression of the studied genes in the BM and LM of both duck breeds. Also, the expression of these three genes showed a positive relationship with the percentage of type IIb fibers and a negative relationship with the percentage of type I fibers and type IIa fibers. Our data indicate differential expression and coordinated developmental regulation of the selected genes involved in the IGF-I-calcineurin-NFATc3 pathway in duck skeletal muscle during embryonic and early PH growth and development; these data also indicate that this signaling pathway might play a role in the regulation of myofiber type transition.

Distribution of CaMKIIα expression in the brain in vivo, studied by CaMKIIα-GFP mice

PubMed Central

Wang, Xinjun; Zhang, Chunzhao; Szábo, Gábor; Sun, Qian-Quan

2013-01-01

To facilitate the study of the CaMKIIα function in vivo, a CaMKIIα-GFP transgenic mouse line was generated. Here, our goal is to provide the first neuroanatomical characterization of GFP expression in the CNS of this line of mouse. Overall, CaMKIIα -GFP expression is strong and highly heterogeneous, with the dentate gyrus of the hippocampus as the most abundantly expressed region. In the hippocampus, around 70% of granule and pyramidal neurons expressed strong GFP. In the neocortex, presumed pyramidal neurons were GFP positive: around 32% of layer II/III and 35% of layer VI neurons expressed GFP, and a lower expression rate was found in other layers. In the thalamus and hypothalamus, strong GFP signals were detected in the neuropil. GFP-positive cells were also found in many other regions such as the spinal trigeminal nucleus, cerebellum and basal ganglia. We further compared the GFP expression with specific antibody staining for CaMKIIα and GABA. We found that GFP+ neurons were mostly positive for CaMKIIα-IR throughout the brain, with some exceptions throughout the brain, especially in the deeper layers of neocortex. GFP and GABA-IR marked distinct neuronal populations in most brain regions with the exception of granule cells in the olfactory bulb, purkinje cells in the cerebellar, and some layer I cells in neocortex. In conclusion, GFP expression in the CaMKIIα-GFP mice is similar to the endogenous expression of CaMKIIα protein, thus these mice can be used in in vivo and in vitro physiological studies in which visualization of CaMKIIα- neuronal populations is required. PMID:23632380

The Influence of Uncompensated Solution Resistance on the Determination and Standard Electrochemical Rate Constants Using Cyclic Voltammetry, and Some Comparisons with AC Voltammetry.

DTIC Science & Technology

1987-09-25

rate constants, k2r using cyclic voltametry . The res tss are expressed in terms of systematic deviations oP sapparent measured" rate constants, k~b(app...concentration was taken to be lum unless otherwise noted. The voltammetric sweep rate was set at 20 V sŕ unless specified otherwise. The general procedure...peaks for the negative- and positive-going potential sweeps have opposite signs, the measured cathodic-anodic peak separation, AEp, will clearly be

Perceived intimacy of expressed emotion.

PubMed

Howell, A; Conway, M

1990-08-01

Research on norms for emotional expression and self-disclosure provided the basis for two hypotheses concerning the perceived intimacy of emotional self-disclosure. The first hypothesis was that the perceived intimacy of negative emotional disclosure would be greater than that of positive emotional disclosure; the second was that disclosures of more intense emotional states would be perceived as more intimate than disclosures of less intense emotional states for both negative and positive disclosures. Both hypotheses received support when male students in Canada rated the perceived intimacy of self-disclosures that were equated for topic and that covered a comprehensive sample of emotions and a range of emotional intensities. The effects were observed across all the topics of disclosure examined.

Energy balance-dependent regulation of ovine glucose 6-phosphate dehydrogenase protein isoform expression.

PubMed

Triantaphyllopoulos, Kostas A; Laliotis, George P; Bizelis, Iosif A

2014-01-01

G6PDH is the rate-limiting enzyme of the pentose phosphate pathway and one of the principal source of NADPH, a major cellular reductant. Importantly, in ruminant's metabolism the aforementioned NADPH provided, is utilized for de novo fatty acid synthesis. Previous work of cloning the ovine (Ovis aries) og6pdh gene has revealed the presence of two cDNA transcripts (og6pda and og6pdb), og6pdb being a product of alternative splicing not similar to any other previously reported.(1) In the current study the effect of energy balance in the ovine G6PDH protein expression was investigated, shedding light on the biochemical features and potential physiological role of the oG6PDB isoform. Changes in energy balance leads to protein expression changes in both transcripts, to the opposite direction and not in a proportional way. Negative energy balance was not in favor of the presence of any particular isoform, while both protein expression levels were not significantly different (P > 0.05). In contrast, at the transition point from negative to positive and on the positive energy balance, there is a significant increase of oG6PDA compared with oG6PDB protein expression (P < 0.001). Both oG6PDH protein isoforms changed significantly toward the positive energy balance. oG6PDA is escalating, while oG6PDB is falling, under the same stimulus (positive energy balance alteration). This change is also positively associated with increasing levels in enzyme activity, 4 weeks post-weaning in ewes' adipose tissue. Furthermore, regression analysis clearly demonstrated the linear correlation of both proteins in response to the WPW, while energy balance, enzyme activity, and oG6PDA relative protein expression follow the same escalating trend; in contrast, oG6PDB relative protein expression falls in time, similar to both transcripts accumulation pattern, as reported previously.(2.)

When feeling bad makes you look good: guilt, shame, and person perception.

PubMed

Stearns, Deborah C; Parrott, W Gerrod

2012-01-01

In two studies, we examined how expressions of guilt and shame affected person perception. In the first study, participants read an autobiographical vignette in which the writer did something wrong and reported feeling either guilt, shame, or no emotion. The participants then rated the writer's motivations, beliefs, and traits, as well as their own feelings toward the writer. The person expressing feelings of guilt or shame was perceived more positively on a number of attributes, including moral motivation and social attunement, than the person who reported feeling no emotion. In the second study, the writer of the vignette reported experiencing (or not experiencing) cognitive and motivational aspects of guilt or shame. Expressing a desire to apologise (guilt) or feelings of worthlessness (private shame) resulted in more positive impressions than did reputational concerns (public shame) or a lack of any of these feelings. Our results indicate that verbal expressions of moral emotions such as guilt and shame influence perception of moral character as well as likeability.

Children’s spontaneous emotional expressions while receiving (un)wanted prizes in the presence of peers

PubMed Central

Visser, Mandy; Krahmer, Emiel; Swerts, Marc

2015-01-01

Although current emotion theories emphasize the importance of contextual factors for emotional expressive behavior, developmental studies that examine such factors are currently thin on the ground. In this research, we studied the course of emotional expressions of 8- and 11-year-old children after winning a (large) first prize or a (substantially smaller) consolation prize, while playing a game competing against the computer or a physically co-present peer. We analyzed their emotional reactions by conducting two perception tests in which participants rated children’s level of happiness. Results showed that co-presence positively affected children’s happiness only when receiving the first prize. Moreover, for children who were in the presence of a peer, we found that eye contact affected children’s expressions of happiness, but that the effect was different for different age groups: 8-year-old children were negatively affected, and 11-year-old children positively. Overall, we can conclude that as children grow older and their social awareness increases, the presence of a peer affects their non-verbal expressions, regardless of their appreciation of their prize. PMID:26441776

Association between CXCL16/CXCR6 expression and the clinicopathological features of patients with non-small cell lung cancer

PubMed Central

Ke, Chuangwu; Ren, Yanchen; Lv, Lu; Hu, Weidong; Zhou, Wenhui

2017-01-01

Lung cancer is a major cause of morbidity and mortality worldwide, therefore identifying biomarkers for the early detection, grading or postoperative follow-up of lung cancer is of clinical significance. In the present study, expression of lung tissue (t)-CXCL16 and t-CXCR6 was examined in 58 patients with non-small cell lung cancer (NSCLC) using immunohistochemical staining, and serum (s)-CXCL16 levels were detected in 58 patients with NSCLC and in 32 normal volunteers using an ELISA. A follow-up was performed every 4 months between January 2014 and January 2015. Compared with the normal volunteers, the s-CXCL16 concentration in patients with NSCLC significantly increased (329.47±135.38 vs. 572.82±116.05 pg/ml, respectively; P<0.001). When grouped according to TNM stage, the expression of t-CXCL16 (60 vs. 85.71%; P=0.029), t-CXCR6 (53.33 vs. 78.57%; P=0.043) and s-CXCL16 (26.67 vs. 57.14%, P=0.019) in the stage I–II subgroup was significantly lower compared with that of the stage III–IV subgroup. The positive expression rate of t-CXCL16 (91.18%) and t-CXCR6 (79.41%) in the lymph node metastasis subgroup was significantly higher compared with that of the corresponding non-lymph node metastasis subgroup (50 and 45.83%, respectively; P<0.01). Additionally, the positive expression rate of t-CXCL16 in the smoking subgroup was 100%, which was significantly higher compared with that of the non-smoking subgroup (23.81%) (P<0.001). The follow-up and mortality rates were 100% (58/58) and 13.79% (8/58), respectively. Within the time period of the present study, the survival time was 4–18 months, and the mean survival time was 16.6 months. In conclusion, the expression of t-CXCL16 and t-CXCR6 is positively correlated with the TNM stage and lymph node metastasis in patients with NSCLC. Additionally, there was a significant increase in s-CXCL16 levels in patients with NSCLC, suggesting that CXCL16 could be used as a supplementary biomarker for the early detection of NSCLC. PMID:28599467

Association between CXCL16/CXCR6 expression and the clinicopathological features of patients with non-small cell lung cancer.

PubMed

Ke, Chuangwu; Ren, Yanchen; Lv, Lu; Hu, Weidong; Zhou, Wenhui

2017-06-01

Lung cancer is a major cause of morbidity and mortality worldwide, therefore identifying biomarkers for the early detection, grading or postoperative follow-up of lung cancer is of clinical significance. In the present study, expression of lung tissue (t)-CXCL16 and t-CXCR6 was examined in 58 patients with non-small cell lung cancer (NSCLC) using immunohistochemical staining, and serum (s)-CXCL16 levels were detected in 58 patients with NSCLC and in 32 normal volunteers using an ELISA. A follow-up was performed every 4 months between January 2014 and January 2015. Compared with the normal volunteers, the s-CXCL16 concentration in patients with NSCLC significantly increased (329.47±135.38 vs. 572.82±116.05 pg/ml, respectively; P<0.001). When grouped according to TNM stage, the expression of t-CXCL16 (60 vs. 85.71%; P=0.029), t-CXCR6 (53.33 vs. 78.57%; P=0.043) and s-CXCL16 (26.67 vs. 57.14%, P=0.019) in the stage I-II subgroup was significantly lower compared with that of the stage III-IV subgroup. The positive expression rate of t-CXCL16 (91.18%) and t-CXCR6 (79.41%) in the lymph node metastasis subgroup was significantly higher compared with that of the corresponding non-lymph node metastasis subgroup (50 and 45.83%, respectively; P<0.01). Additionally, the positive expression rate of t-CXCL16 in the smoking subgroup was 100%, which was significantly higher compared with that of the non-smoking subgroup (23.81%) (P<0.001). The follow-up and mortality rates were 100% (58/58) and 13.79% (8/58), respectively. Within the time period of the present study, the survival time was 4-18 months, and the mean survival time was 16.6 months. In conclusion, the expression of t-CXCL16 and t-CXCR6 is positively correlated with the TNM stage and lymph node metastasis in patients with NSCLC. Additionally, there was a significant increase in s-CXCL16 levels in patients with NSCLC, suggesting that CXCL16 could be used as a supplementary biomarker for the early detection of NSCLC.

Predictive values of FAP and HGF for tumor angiogenesis and metastasis in colorectal cancer.

PubMed

Ma, T H; Gao, C C; Xie, R; Yang, X Z; Dai, W J; Zhang, J L; Yan, W; Wu, S N

2017-01-01

This study aims to explore the correlation of hepatocyte growth factor (HGF) and fibroblast activation protein (FAP) expressions with the angiogenesis and metastasis in colorectal cancer (CRC). The immunohistochemical SABC method was used to detect HGF and FAP expressions in 127 CRC tissues, 51 colorectal polyp tissues and 28 normal tissues. HGF and FAP expressions in liver metastasis were detected using western blot to analyze the correlation of their expressions with lymph node metastasis and liver metastasis. Micro-vessel density (MVD) and clinic-pathologic information of CRC patients were recorded and analyzed. In CRC group, HGF and FAP expressions were greatly higher than those in normal group and colorectal polyps group (P < 0.05). Moreover, the positive rates of HGF and FAP expressions in lymph node metastasis were evidently higher than those in non-lymph node metastasis (P < 0.05). In liver metastasis group, HGF and FAP expressions were obviously higher than non-liver metastasis group (P < 0.05). CRC group had much more MVD in comparison with normal group and colorectal polyps group (P < 0.05).When compared with negative group, MVD was significantly higher than that in CRC tissue with positive HGF and FAP (P < 0.05). Spearman rank correlation analysis showed that HGF and FAP were in positive correlation with MVD (r = 0.542, P < 0.001; r = 0.753, P < 0.001). These results indicate that FAP and HGF play an important role in CRC angiogenesis, and their expression levels are valuable to predict CRC liver metastasis and lymph node metastasis.

Differences in Expressivity Based on Attractiveness: Target or Perceiver Effects?

PubMed

Rennels, Jennifer L; Kayl, Andrea J

2015-09-01

A significant association exists between adults' expressivity and facial attractiveness, but it is unclear whether the association is linear or significant only at the extremes of attractiveness. It is also unclear whether attractive persons actually display more positive expressivity than unattractive persons (target effects) or whether high and low attractiveness influences expressivity valence judgments (perceiver effects). Experiment 1 demonstrated adult ratings of attractiveness were predictive of expressivity valence only for high and low attractive females and medium attractive males. Experiment 2 showed that low attractive females actually display more negative expressivity than medium and high attractive females, but there were no target effects for males. Also, attractiveness influenced expressivity valence judgments (perceiver effects) for both females and males. Our findings demonstrate that low attractive females are at a particular disadvantage during social interactions due to their low attractiveness, actual displays of negative expressivity, and perceptions of their negative expressivity.

Differences in Expressivity Based on Attractiveness: Target or Perceiver Effects?

PubMed Central

Rennels, Jennifer L.; Kayl, Andrea J.

2015-01-01

A significant association exists between adults’ expressivity and facial attractiveness, but it is unclear whether the association is linear or significant only at the extremes of attractiveness. It is also unclear whether attractive persons actually display more positive expressivity than unattractive persons (target effects) or whether high and low attractiveness influences expressivity valence judgments (perceiver effects). Experiment 1 demonstrated adult ratings of attractiveness were predictive of expressivity valence only for high and low attractive females and medium attractive males. Experiment 2 showed that low attractive females actually display more negative expressivity than medium and high attractive females, but there were no target effects for males. Also, attractiveness influenced expressivity valence judgments (perceiver effects) for both females and males. Our findings demonstrate that low attractive females are at a particular disadvantage during social interactions due to their low attractiveness, actual displays of negative expressivity, and perceptions of their negative expressivity. PMID:26366010

KDEF-PT: Valence, Emotional Intensity, Familiarity and Attractiveness Ratings of Angry, Neutral, and Happy Faces.

PubMed

Garrido, Margarida V; Prada, Marília

2017-01-01

The Karolinska Directed Emotional Faces (KDEF) is one of the most widely used human facial expressions database. Almost a decade after the original validation study (Goeleven et al., 2008), we present subjective rating norms for a sub-set of 210 pictures which depict 70 models (half female) each displaying an angry, happy and neutral facial expressions. Our main goals were to provide an additional and updated validation to this database, using a sample from a different nationality ( N = 155 Portuguese students, M = 23.73 years old, SD = 7.24) and to extend the number of subjective dimensions used to evaluate each image. Specifically, participants reported emotional labeling (forced-choice task) and evaluated the emotional intensity and valence of the expression, as well as the attractiveness and familiarity of the model (7-points rating scales). Overall, results show that happy faces obtained the highest ratings across evaluative dimensions and emotion labeling accuracy. Female (vs. male) models were perceived as more attractive, familiar and positive. The sex of the model also moderated the accuracy of emotional labeling and ratings of different facial expressions. Each picture of the set was categorized as low, moderate, or high for each dimension. Normative data for each stimulus (hits proportion, means, standard deviations, and confidence intervals per evaluative dimension) is available as supplementary material (available at https://osf.io/fvc4m/).

Prognostic Significance of Progesterone Receptor–Positive Tumor Cells Within Immunohistochemically Defined Luminal A Breast Cancer

PubMed Central

Prat, Aleix; Cheang, Maggie Chon U.; Martín, Miguel; Parker, Joel S.; Carrasco, Eva; Caballero, Rosalía; Tyldesley, Scott; Gelmon, Karen; Bernard, Philip S.; Nielsen, Torsten O.; Perou, Charles M.

2013-01-01

Purpose Current immunohistochemical (IHC)-based definitions of luminal A and B breast cancers are imperfect when compared with multigene expression-based assays. In this study, we sought to improve the IHC subtyping by examining the pathologic and gene expression characteristics of genomically defined luminal A and B subtypes. Patients and Methods Gene expression and pathologic features were collected from primary tumors across five independent cohorts: British Columbia Cancer Agency (BCCA) tamoxifen-treated only, Grupo Español de Investigación en Cáncer de Mama 9906 trial, BCCA no systemic treatment cohort, PAM50 microarray training data set, and a combined publicly available microarray data set. Optimal cutoffs of percentage of progesterone receptor (PR) –positive tumor cells to predict survival were derived and independently tested. Multivariable Cox models were used to test the prognostic significance. Results Clinicopathologic comparisons among luminal A and B subtypes consistently identified higher rates of PR positivity, human epidermal growth factor receptor 2 (HER2) negativity, and histologic grade 1 in luminal A tumors. Quantitative PR gene and protein expression were also found to be significantly higher in luminal A tumors. An empiric cutoff of more than 20% of PR-positive tumor cells was statistically chosen and proved significant for predicting survival differences within IHC-defined luminal A tumors independently of endocrine therapy administration. Finally, no additional prognostic value within hormonal receptor (HR) –positive/HER2-negative disease was observed with the use of the IHC4 score when intrinsic IHC-based subtypes were used that included the more than 20% PR-positive tumor cells and vice versa. Conclusion Semiquantitative IHC expression of PR adds prognostic value within the current IHC-based luminal A definition by improving the identification of good outcome breast cancers. The new proposed IHC-based definition of luminal A tumors is HR positive/HER2 negative/Ki-67 less than 14%, and PR more than 20%. PMID:23233704

The Emotional Child Witness Effect Survives Presentation Mode.

PubMed

Melinder, Annika; Burrell, Lisa; Eriksen, Maria Olaussen; Magnussen, Svein; Wessel, Ellen

2016-01-01

The emotional witness effect - the phenomenon whereby people are affected by the emotional manner in which a witness presents testimony - constitutes a possible source of wrongful decisions in legal contexts. One stereotypical view of abused children is that they should be sad when talking about their experiences of maltreatment, whereas children may in fact express a variety of emotional expressions when talking about abusive events. This raises the question as to whether there is an optimal mode in which to present child victim testimony that could reduce the possible influence of displayed emotions. In the present study, mock police interviews were carried out with female child actors, role-playing the victims of physical abuse by their stepfather, telling the same story with four emotional expressions (neutral, sad, angry, or positive). Laypersons (N = 465) were presented with the interviews as transcripts with the emotional reactions of the child witness noted, audio recordings, or videotaped recordings. Participants then rated the credibility of the victim witness. Replicating previous results, the "sad" expression elicited the highest credibility ratings across all modes of presentations. Presentation mode affected ratings of credibility, with the transcript versions resulting in the highest ratings. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Functional Alterations of Postcentral Gyrus Modulated by Angry Facial Expressions during Intraoral Tactile Stimuli in Patients with Burning Mouth Syndrome: A Functional Magnetic Resonance Imaging Study

PubMed Central

Yoshino, Atsuo; Okamoto, Yasumasa; Doi, Mitsuru; Okada, Go; Takamura, Masahiro; Ichikawa, Naho; Yamawaki, Shigeto

2017-01-01

Previous findings suggest that negative emotions could influence abnormal sensory perception in burning mouth syndrome (BMS). However, few studies have investigated the underlying neural mechanisms associated with BMS. We examined activation of brain regions in response to intraoral tactile stimuli when modulated by angry facial expressions. We performed functional magnetic resonance imaging on a group of 27 BMS patients and 21 age-matched healthy controls. Tactile stimuli were presented during different emotional contexts, which were induced via the continuous presentation of angry or neutral pictures of human faces. BMS patients exhibited higher tactile ratings and greater activation in the postcentral gyrus during the presentation of tactile stimuli involving angry faces relative to controls. Significant positive correlations between changes in brain activation elicited by angry facial images in the postcentral gyrus and changes in tactile rating scores by angry facial images were found for both groups. For BMS patients, there was a significant positive correlation between changes in tactile-related activation of the postcentral gyrus elicited by angry facial expressions and pain intensity in daily life. Findings suggest that neural responses in the postcentral gyrus are more strongly affected by angry facial expressions in BMS patients, which may reflect one possible mechanism underlying impaired somatosensory system function in this disorder. PMID:29163243

Second Language Ability and Emotional Prosody Perception

PubMed Central

Bhatara, Anjali; Laukka, Petri; Boll-Avetisyan, Natalie; Granjon, Lionel; Anger Elfenbein, Hillary; Bänziger, Tanja

2016-01-01

The present study examines the effect of language experience on vocal emotion perception in a second language. Native speakers of French with varying levels of self-reported English ability were asked to identify emotions from vocal expressions produced by American actors in a forced-choice task, and to rate their pleasantness, power, alertness and intensity on continuous scales. Stimuli included emotionally expressive English speech (emotional prosody) and non-linguistic vocalizations (affect bursts), and a baseline condition with Swiss-French pseudo-speech. Results revealed effects of English ability on the recognition of emotions in English speech but not in non-linguistic vocalizations. Specifically, higher English ability was associated with less accurate identification of positive emotions, but not with the interpretation of negative emotions. Moreover, higher English ability was associated with lower ratings of pleasantness and power, again only for emotional prosody. This suggests that second language skills may sometimes interfere with emotion recognition from speech prosody, particularly for positive emotions. PMID:27253326

Miki (Mitotic Kinetics Regulator) Immunoexpression in Normal Liver, Cirrhotic Areas and Hepatocellular Carcinomas: a Preliminary Study with Clinical Relevance.

PubMed

Fernández-Vega, Iván; Santos-Juanes, Jorge; Camacho-Urkaray, Emma; Lorente-Gea, Laura; García, Beatriz; Gutiérrez-Corres, Francisco Borja; Quirós, Luis M; Guerra-Merino, Isabel; Aguirre, José Javier

2018-02-12

Hepatocellular carcinoma (HCC) is the most common type of primary malignant tumor in the liver. One of the main features of cancer survival is the generalized loss of growth control exhibited by cancer cells, and Miki is a protein related to the immunoglobulin superfamily that plays an important role in mitosis. We aim to study protein expression levels of Miki in non-tumoral liver and 20 HCCs recruited from a Pathology Department. Clinical information was also obtained. A tissue microarray was performed, and immunohistochemical techniques applied to study protein expression levels of Miki. In normal liver, Miki was weakly expressed, showing nuclear staining in the hepatocytes. Cirrhotic areas and HCCs showed a variety of staining patterns. Most HCC samples showed positive expression, with three different staining patterns being discernible: nuclear, cytoplasmic and mixed. Statistical analysis showed a significant association between grade of differentiation, Ki-67 proliferative index, survival rates and staining patterns. This study has revealed the positive expression of Miki in normal liver, cirrhotic areas and HCCs. Three different staining patterns of Miki expression with clinical relevance were noted in HCCs.

KDM4B and KDM4A promote endometrial cancer progression by regulating androgen receptor, c-myc, and p27kip1

PubMed Central

Kwan, Suet-Ying; Chen, Limo; Chen, Jin-Hong; Ying, Zuo-Lin; Zhou, Ye; Gu, Wei; Wang, Li-Hua; Cheng, Wei-Wei; Zeng, Jianfang; Wan, Xiao-Ping; Mok, Samuel C.; Wong, Kwong-Kwok; Bao, Wei

2015-01-01

Epidemiological evidence suggests that elevated androgen levels and genetic variation related to the androgen receptor (AR) increase the risk of endometrial cancer (EC). However, the role of AR in EC is poorly understood. We report that two members of the histone demethylase KDM4 family act as major regulators of AR transcriptional activityin EC. In the MFE-296 cell line, KDM4B and AR upregulate c-myc expression, while in AN3CA cells KDM4A and AR downregulate p27kip1. Additionally, KDM4B expression is positively correlated with AR expression in EC cell lines with high baseline AR expression, while KDM4A and AR expression are positively correlated in low-AR cell lines. In clinical specimens, both KDM4B and KDM4A expression are significantly higher in EC tissues than that in normal endometrium. Finally, patients with alterations in AR, KDM4B, KDM4A, and c-myc have poor overall and disease-free survival rates. Together, these findings demonstrate that KDM4B and KDM4A promote EC progression by regulating AR activity. PMID:26397136

[Expression of ephrin-A7 and metadherin and its clinicopathological significances in the benign and malignant lesions of gallbladder].

PubMed

Liu, Dong-cai; Yang, Zhu-lin

2011-03-01

To study the expression of ephrin-A7 (EphA7) and metadherin (MTDH) and their clinicopathological significances in the benign and malignant lesions of gallbladder. EnVisiom immunohistochemical methods was used for determining the expressions of EphA7 and MTDH in routinely paraffin-embedded sections of surgically-resected specimens from 108 cases with gallbladder adenocarcinoma, 15 cases with adenomatous polyp and 35 cases with chronic cholecystitis treated from June 1996 to June 2006. And 46 cases of peritumoral tissues were also harvested as controls (n = 35). The positive expression rates of EphA7 and MTDH were significantly higher in gallbladder adenocarcinoma than those in peritumoral tissues (χ(2)(EphA7) = 12.65, χ(2)(MTDH) = 13.00; P < 0.01), adenomatous polyp (χ(2)(EphA7) = 8.21, χ(2)(MTDH) = 9.39; P < 0.01) and chronic cholecystitis (χ(2)(EphA7) = 21.21, χ(2)(MTDH) = 23.68; P < 0.01); Moderately-or severely-atypical hyperplasia of gallbladder epithelium was found in the benign lesions with positive expression of EphA7 and/or MTDH. The positive rates of EphA7 and MTDH were significantly lower in the cases of well-differentiated adenocarcinoma, maximal diameter of tumor < 2 cm, no-metastasis of lymph node, and tumor with no-invasiveness of regional tissues than those in the poorly-differentiated adenocarcinoma (χ(2)(EphA7) = 12.34, χ(2)(MTDH) = 12.80; P < 0.01), maximal diameter of tumor ≥ 2 cm (χ(2)(EphA7) = 5.22, χ(2)(MTDH) = 5.00; P < 0.05), cases with metastasis of lymph node (χ(2)(EphA7) = 5.15, χ(2)(MTDH) = 5.86; P < 0.05) and cases with invasiveness of regional tissues (χ(2)(EphA7) = 7.06, P < 0.01; χ(2)(MTDH) = 4.13; P < 0.05) in gallbladder adenocarcinoma (P < 0.05). The high consistency was found between the expressive levels of EphA7 and MTDH in gallbladder adenocarcinoma (χ(2) = 13.11, P < 0.01). The univariate Kaplan-Meier analysis showed that the increased expression of EphA7 (P = 0.023) and MTDH (P = 0.034) was negatively associated with the overall survival. The multivariate Cox regression analysis showed that increased expression of EphA7 and/or MTDH (P(EphA2) = 0.023, P(MTDH) = 0.034) was an independent poor-prognostic predictor for gallbladder adenocarcinoma. The expression of EphA7 and/or MTDH might be closely related to the carcinogenesis, progression, clinical biological behaviors and prognosis of gallbladder adenocarcinoma. The positive expression of EphA7 and/or MTDH may predict bad-prognosis in gallbladder adenocarcinoma.

Expression of p53 and selected proliferative markers (Ki-67, MCM3, PCNA, and topoisomerase IIα) in borderline ovarian tumors: Correlation with clinicopathological features.

PubMed

Ciepliński, Klaudiusz; Jóźwik, Maciej; Semczuk-Sikora, Anna; Gogacz, Marek; Lewkowicz, Dorota; Ignatov, Atanas; Semczuk, Andrzej

2018-02-01

The expression of p53 has been studied not only in primary human ovarian carcinomas, but also in borderline ovarian tumors, however, the results were discordant. Expression patterns of proteins involved in cell proliferation and apoptosis have been investigated in various human neoplasms, including female genital tract neoplasms. The aim of this investigation was to assess the staining pattern and immunolocalization of p53 and selected proliferative markers (Ki-67, MCM3, PCNA, and topoisomerase IIα) in borderline ovarian tumors (BOTs). The study group consisted of 42 women who underwent pelvic surgery between 2006-2015. The median patients' age was 46 years. The immunoperoxidase technique was employed using antibodies against p53, Ki-67, MCM3, PCNA, and topoisomerase IIα. For p53, nuclear expression was observed in BOTs, however, cytoplasmatic immunoreactivity was also detected. Altogether, 25 (60%) tumors demonstrated positive p53 immunostaining, including overexpression found in 6 (14%). There were no significant differences in p53 expression between subgroups of clinicopathological variables. Immunoexpression of Ki-67, MCM3, PCNA, and topoisomerase IIα was nuclear. Ki-67 expression was positive in 12 (29%) cases and there was a trend towards a relationship between patients' age and Ki-67 staining (P=0.08). Interestingly, a significantly higher Ki-67 expression was found in tumors of ≥10 cm in diameter compared to smaller tumors (P=0.008). MCM3 expression was detected in 38 (90%) tumors, and PCNA expression in 28 (67%), yet none of clinicopathological factors was related to them. Topoisomerase IIα expression was present in 14 (33%) cases and, interestingly, its significantly higher expression was observed in BOTs of ≥10 cm in diameter compared to smaller tumors (P=0.008). Moreover, Spearman's correlation revealed highly significant positive associations between Ki-67 and topoisomerase IIα (R=0.403, P=0.008) and Ki-67 and MCM3 (R=0.469, P=0.001). We report a high positive immunostaining rate for p53, suggesting a role of TP53 alterations in the development of BOTs in humans. The new finding of higher topoisomerase IIα immunostaining positivity in BOTs of ≥10 cm may be clinically relevant and requires further studies on larger patient groups.

Controlling false-negative errors in microarray differential expression analysis: a PRIM approach.

PubMed

Cole, Steve W; Galic, Zoran; Zack, Jerome A

2003-09-22

Theoretical considerations suggest that current microarray screening algorithms may fail to detect many true differences in gene expression (Type II analytic errors). We assessed 'false negative' error rates in differential expression analyses by conventional linear statistical models (e.g. t-test), microarray-adapted variants (e.g. SAM, Cyber-T), and a novel strategy based on hold-out cross-validation. The latter approach employs the machine-learning algorithm Patient Rule Induction Method (PRIM) to infer minimum thresholds for reliable change in gene expression from Boolean conjunctions of fold-induction and raw fluorescence measurements. Monte Carlo analyses based on four empirical data sets show that conventional statistical models and their microarray-adapted variants overlook more than 50% of genes showing significant up-regulation. Conjoint PRIM prediction rules recover approximately twice as many differentially expressed transcripts while maintaining strong control over false-positive (Type I) errors. As a result, experimental replication rates increase and total analytic error rates decline. RT-PCR studies confirm that gene inductions detected by PRIM but overlooked by other methods represent true changes in mRNA levels. PRIM-based conjoint inference rules thus represent an improved strategy for high-sensitivity screening of DNA microarrays. Freestanding JAVA application at http://microarray.crump.ucla.edu/focus

Expression of calcium binding protein S100 A7 (psoriasin) in laryngeal carcinoma.

PubMed

Tiveron, Rogério Costa; de Freitas, Luiz Carlos Conti; Figueiredo, David L; Serafini, Luciano N; Mamede, Rui Celso Martins; Zago, Marco A

2012-01-01

Many studies have reported increased expression of S100 A7 (psoriasin) in neoplastic lesions. Among them are studies on breast carcinoma, bladder squamous cell carcinoma, skin tumors and oral cavity squamous cell carcinoma. The expression of S100 A7 has not been described for laryngeal cancer. This study aims to identify the expression of the calcium-binding protein S100 A7 and its correlation with squamous cell carcinomas of the larynx. Specimens from 63 patients were submitted to immunohistochemistry testing with antibody S100 A7. Results were classified and compared. The group with highly differentiated tumors had the highest treatment failure scores. Moderately differentiated tumors had higher treatment failure scores than poorly differentiated tumors. Higher scores were predominantly seen on stages I and II in moderately differentiated tumors, whereas score distribution was more homogeneous in advanced stage disease (III and IV). Regarding failure in treatment, the group scoring zero (3/4 complications: 75%) differed significantly from the remaining groups (13/59: 22%). S100 A7 marker was expressed in 93.7% of laryngeal cancer cases, with higher positive correlation rates in more differentiated tumors and significantly lower rates of treatment failure. Scores had no impact on survival rates.

Optical contrast agents to visualize molecular expression in breast cancer

NASA Astrophysics Data System (ADS)

Langsner, Robert James

Breast cancer is the second leading cause of death of women in the United States. Improvements in screening technology have increased the breast cancer incidence rate, as smaller lesions are being detected. Due to the small size of lesions, patients can choose to receive breast conservation therapy (BCT) rather than a modified radical mastectomy. Even though the breast retains cosmesis after BCT, there is an increased risk of the patient having residual microscopic disease, known as positive margins. Patients with positive margins receive increased radiation and have an increased chance of second surgery. Pathology with hematoxylin and eosin (H&E) remains the gold standard for diagnosing margin status in patients. Intraoperative pathology has been shown to reduce the rate of positive margins in BCT. However, a minority of surgery centers have intraoperative pathology centers, limiting the number of patients that receive this standard of care. The expression profiles of surface receptors such as ErbB2 (HER2-positive) and epidermal growth factor receptor (EGFR) provide information about the aggressiveness of a particular tumor. Recent research has shown that there was elevated EGFR expression in patients with a local recurrence even though the biopsies were assessed to be disease free using standard H&E. If the physicians had known the molecular expression of these biopsies, a different treatment regimen or excision of more tissue might have prevented the recurrence. This thesis investigates targeted molecular contrast agents that enhance the visualization of molecular markers such as glucose transporters (GLUTs) and growth factor receptors in tissue specimens. First, application of 2-NBDG, a fluorescent deoxyglucose, enhances signal in cancerous tissue with a 20-minute incubation. Then, antibody functionalized silica-gold nanoshells enhance the visualization of ErbB2 overexpression in specimens with a 5-minute incubation. To image these contrast agents in cancerous tissue, a portable, inexpensive device was developed as a tool to help physicians visualize expression of surface markers. The system visualizes absorbance from nanoshell aggregates and fluorescence in the visible and near-infrared light spectrum. This study represents the first step in the development of an intraoperative optical imaging device to enhance the visualization of molecular markers overexpressed in cancerous cells.

Multifunctional imaging signature for V-KI-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in colorectal cancer.

PubMed

Miles, Kenneth A; Ganeshan, Balaji; Rodriguez-Justo, Manuel; Goh, Vicky J; Ziauddin, Zia; Engledow, Alec; Meagher, Marie; Endozo, Raymondo; Taylor, Stuart A; Halligan, Stephen; Ell, Peter J; Groves, Ashley M

2014-03-01

This study explores the potential for multifunctional imaging to provide a signature for V-KI-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutations in colorectal cancer. This prospective study approved by the institutional review board comprised 33 patients undergoing PET/CT before surgery for proven primary colorectal cancer. Tumor tissue was examined histologically for presence of the KRAS mutations and for expression of hypoxia-inducible factor-1 (HIF-1) and minichromosome maintenance protein 2 (mcm2). The following imaging parameters were derived for each tumor: (18)F-FDG uptake ((18)F-FDG maximum standardized uptake value [SUVmax]), CT texture (expressed as mean of positive pixels [MPP]), and blood flow measured by dynamic contrast-enhanced CT. A recursive decision tree was developed in which the imaging investigations were applied sequentially to identify tumors with KRAS mutations. Monte Carlo analysis provided mean values and 95% confidence intervals for sensitivity, specificity, and accuracy. The final decision tree comprised 4 decision nodes and 5 terminal nodes, 2 of which identified KRAS mutants. The true-positive rate, false-positive rate, and accuracy (95% confidence intervals) of the decision tree were 82.4% (63.9%-93.9%), 0% (0%-10.4%), and 90.1% (79.2%-96.0%), respectively. KRAS mutants with high (18)F-FDG SUVmax and low MPP showed greater frequency of HIF-1 expression (P = 0.032). KRAS mutants with low (18)F-FDG SUV(max), high MPP, and high blood flow expressed mcm2 (P = 0.036). Multifunctional imaging with PET/CT and recursive decision-tree analysis to combine measurements of tumor (18)F-FDG uptake, CT texture, and perfusion has the potential to identify imaging signatures for colorectal cancers with KRAS mutations exhibiting hypoxic or proliferative phenotypes.

[The efficacy of autocatalytic casapse-3 driven by human telomerase reverse transcriptase promoter on human ovarian carcinoma].

PubMed

Song, Yue; Shen, Keng; Yu, Jing-rong

2007-11-06

To construct recombinant adenoviral vector expressing autocatalysis caspase-3 driven by human telomerase reverse transcriptase promoter (hTERTp), and investigate its antitumor effect on ovarian cancer in vitro and in vivo. Recombinant adenovirus expressing autocatalytic caspase-3 (rev-csapase-3) driven by hTERTp, AdHT-rev-casp3, was constructed. Ad-rev-casp3 expressing rev-caspase-3 driven by cytomegalovirus promoter (CMVp) was used as a positive control. hTERT positive human ovarian cancer cells of the line AO and hTERT-negative human umbilical venous endothelial cells (HUVECs) were cultured and transfected with AdHT-rev-casp3, Ad-rev-casp3, or Ad-EGFG expressing enhanced green fluorescent protein as control group. Western blotting, Cell Counting Kit (CCK-8), flow cytometry, and TUNEL were used to detect the expression of p17, active subunit of caspase-3, and p85, a poly ADP-ribose polymerase (PARP) cleavage fragment, and they were also used to measure the cell survival rate and apoptotic rate. Western blotting was used to detect the expression of active caspase-3 and its substrate PARP in the AO cells and HUVECs. Twenty nude BALB/c mice were inoculated subcutaneously with AO cells to establish subcutaneous tumor models, when the tumor grew to the volume of 150 mm3 the rats were divided into 4 equal groups to undergo intra-tumor injection of AdHT-rev-casp3, Ad-rev-casp3, Ad-EGFG, and phosphate-buffered saline (PBS) respectively, the survival rate tumor inhibition rate was observed, 72 days later the mice were killed with their livers and tumors taken out, and Western blotting was used to detect the expression of active caspase-3. Another 40 mice underwent intraperitoneal injection of AO cells to establish intraperitoneal transplanted tumor models, 21 days later the rats were divided into 4 equal groups to be injected intraperitoneally with AdHT-rev-casp3, Ad-rev-casp3, Ad-EGFG, or PBS, the survival rate was observed, and the blood levels of alanine transaminase (ALT) and aspartate transaminase (AST) were detected. Following the administration of AdHT-rev-casp3, active caspase-3 protein was significantly expressed, and the levels of p17 and p85 expressions were significantly elevated in AO cells, while no expressions of p17 and p85 was observed in HUVEC. In contrast, both AO and HUVEC expressed high levels of p17 and p85 protein after administrations of Ad-rev-casp3. AdHT-rev-casp3 dose-dependently killed the hTERT positive AO cells, however, showed no killing effect on the hTERT-negative HUVEC cells; whereas Ad-rev-casp3 was cytotoxic independent of the hTERT status of the cells. The killing effect of Ad-rev-casp3 was stronger than that of AdHT-rev-casp3. Treated with AdHT-rev-cap3 the expression levels of the caspase-3 fragment p17 and PARP cleavage fragment p85 of the AO cells were significantly higher than those before the treatment, however, the expression levels of p17 and p85 were both weaker than those of the AO cells treated with Ad-rev-casp-3. Though treated with AdHT-rev-casp-3, there was still no remarkable expression of p17 and p85 in the HUVECs, however, rather high protein expression levels of p17 and p85 was shown. After treatment with AdHT-rev-casp3 remarkable expression of active caspase-3 was seen in the tumor collected from the mouse body, but not in the liver; however, high caspase-3 expression level was shown in both the liver and tumor after the treatment of Ad-rev-casp-3. 53 days after treatment the tumor suppression rate of the AdHT-rev-casp3 and ad-rev-casp-3 groups were 60% and 70% respectively, both significantly higher than that of the control group. The survival rates of the mice treated with AdHT-rev-casp3 and Ad-rev-casp-3 were both significantly longer than that of the PBS group; however the survival rate of the Ad-rev-casp-3 group was longer than that of the AdHT-rev-casp3 group. The serum ALT and AST levels were not significantly elevated in the AdHT-rev-casp3-treated mice, whereas 7-9-times that before treatment in the Ad-rev-casp3-treated mice. Recombinant adenovirus AdHT-rev-casp3 expressing rev-caspase-3 driven by hTERTp effectively causes cell apoptosis targeting tumor, significantly suppresses tumor growth and prolongs the mouse survival duration, with mild liver toxicity.

Radial growth rate increases in naturally occurring ponderosa pine trees: a late-20th century CO2 fertilization effect?

PubMed

Soulé, Peter T; Knapp, Paul A

2006-01-01

The primary objective of this study was to determine if gradually increasing levels of atmospheric CO2, as opposed to 'step' increases commonly employed in controlled studies, have a positive impact on radial growth rates of ponderosa pine (Pinus ponderosa) in natural environments, and to determine the spatial extent and variability of this growth enhancement. We developed a series of tree-ring chronologies from minimally disturbed sites across a spectrum of environmental conditions. A series of difference of means tests were used to compare radial growth post-1950, when the impacts of rising atmospheric CO2 are best expressed, with that pre-1950. Spearman's correlation was used to relate site stress to growth-rate changes. Significant increases in radial growth rates occurred post-1950, especially during drought years, with the greatest increases generally found at the most water-limited sites. Site harshness is positively related to enhanced radial growth rates. Atmospheric CO2 fertilization is probably operative, having a positive effect on radial growth rates of ponderosa pine through increasing water-use efficiency. A CO2-driven growth enhancement may affect ponderosa pine growing under both natural and controlled conditions.

Major depressive disorder skews the recognition of emotional prosody.

PubMed

Péron, Julie; El Tamer, Sarah; Grandjean, Didier; Leray, Emmanuelle; Travers, David; Drapier, Dominique; Vérin, Marc; Millet, Bruno

2011-06-01

Major depressive disorder (MDD) is associated with abnormalities in the recognition of emotional stimuli. MDD patients ascribe more negative emotion but also less positive emotion to facial expressions, suggesting blunted responsiveness to positive emotional stimuli. To ascertain whether these emotional biases are modality-specific, we examined the effects of MDD on the recognition of emotions from voices using a paradigm designed to capture subtle effects of biases. Twenty-one MDD patients and 21 healthy controls (HC) underwent clinical and neuropsychological assessments, followed by a paradigm featuring pseudowords spoken by actors in five types of emotional prosody, rated on continuous scales. Overall, MDD patients performed more poorly than HC, displaying significantly impaired recognition of fear, happiness and sadness. Compared with HC, they rated fear significantly more highly when listening to anger stimuli. They also displayed a bias toward surprise, rating it far higher when they heard sad or fearful utterances. Furthermore, for happiness stimuli, MDD patients gave higher ratings for negative emotions (fear and sadness). A multiple regression model on recognition of emotional prosody in MDD patients showed that the best fit was achieved using the executive functioning (categorical fluency, number of errors in the MCST, and TMT B-A) and the total score of the Montgomery-Asberg Depression Rating Scale. Impaired recognition of emotions would appear not to be specific to the visual modality but to be present also when emotions are expressed vocally, this impairment being related to depression severity and dysexecutive syndrome. MDD seems to skew the recognition of emotional prosody toward negative emotional stimuli and the blunting of positive emotion appears not to be restricted to the visual modality. Copyright © 2011 Elsevier Inc. All rights reserved.

Early versus late distant metastasis and adjuvant chemotherapy alone versus both radiotherapy and chemotherapy in molecular apocrine breast cancer

PubMed Central

Liu, Xiaozhen; Yang, Yang; Feng, Xiaolong; Shen, Honghong; Liu, Jian; Liu, Xia; Niu, Yun

2016-01-01

As a new subtype of breast cancer, molecular apocrine breast cancer (MABC) is estrogen receptor (ER) and progesterone receptor (PR) negative expression, but androgen receptor (AR) positive expression. The prognostic significance and clinical biological behavior of MABC have remained unclear up to now. This study aimed to analysis the distant metastasis behavior and response to adjuvant radiotherapy and chemotherapy of MABC subgroup. The report showed that there were significant differences between early and late distant metastasizing tumors with respect to Ki67, epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor (VEGF) expressions by a retrospective analysis consisting of 410 invasive breast cancer patients, which included 205 MABC and 205 nonMABC cases. MABC subgroup metastasized earlier than nonMABC subgroup, and MABC showed a tendency for a higher metastasis rate in lung, liver and brain, but lower in bone. HER2-positive or VEGF-positive tumors were more inclined to develop bone metastasis within MABC subgroup. The survival rate was superior for patients undergone both adjuvant radiotherapy and chemotherapy than those undergone chemotherapy alone in nonMABC subgroup, but there was no significant difference in MABC subgroup. Our data suggested that MABC subgroup seemed to develop distant metastasis earlier than nonMABC subgroup, and patients with MABC indicated poor prognosis. This study might also provide a foundation for helping patients receive reasonable treatments according to molecular subtype. PMID:27340922

Early versus late distant metastasis and adjuvant chemotherapy alone versus both radiotherapy and chemotherapy in molecular apocrine breast cancer.

PubMed

Liu, Xiaozhen; Yang, Yang; Feng, Xiaolong; Shen, Honghong; Liu, Jian; Liu, Xia; Niu, Yun

2016-08-02

As a new subtype of breast cancer, molecular apocrine breast cancer (MABC) is estrogen receptor (ER) and progesterone receptor (PR) negative expression, but androgen receptor (AR) positive expression. The prognostic significance and clinical biological behavior of MABC have remained unclear up to now. This study aimed to analysis the distant metastasis behavior and response to adjuvant radiotherapy and chemotherapy of MABC subgroup. The report showed that there were significant differences between early and late distant metastasizing tumors with respect to Ki67, epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor (VEGF) expressions by a retrospective analysis consisting of 410 invasive breast cancer patients, which included 205 MABC and 205 nonMABC cases. MABC subgroup metastasized earlier than nonMABC subgroup, and MABC showed a tendency for a higher metastasis rate in lung, liver and brain, but lower in bone. HER2-positive or VEGF-positive tumors were more inclined to develop bone metastasis within MABC subgroup. The survival rate was superior for patients undergone both adjuvant radiotherapy and chemotherapy than those undergone chemotherapy alone in nonMABC subgroup, but there was no significant difference in MABC subgroup. Our data suggested that MABC subgroup seemed to develop distant metastasis earlier than nonMABC subgroup, and patients with MABC indicated poor prognosis. This study might also provide a foundation for helping patients receive reasonable treatments according to molecular subtype.

Predictive Value of Tertiary Lymphoid Structures Assessed by High Endothelial Venule Counts in the Neoadjuvant Setting of Triple-Negative Breast Cancer

PubMed Central

Song, In Hye; Heo, Sun-Hee; Bang, Won Seon; Park, Hye Seon; Park, In Ah; Kim, Young-Ae; Park, Suk Young; Roh, Jin; Gong, Gyungyub; Lee, Hee Jin

2017-01-01

Purpose The tertiary lymphoid structure (TLS) is an important source of tumor-infiltrating lymphocytes (TILs), which have a strong prognostic and predictive value in triple-negative breast cancer (TNBC). A previous study reported that the levels of CXCL13 mRNA expression were associated with TLSs, but measuring the gene expression is challenging in routine practice. Therefore, this study evaluated the MECA79-positive high endothelial venule (HEV) densities and their association with the histopathologically assessed TLSs in biopsy samples. In addition, the relationship of TLSs with the CXCL13 transcript levels and clinical outcomes were examined. Materials and Methods A total of 108 TNBC patients treated with neoadjuvant chemotherapy (NAC) were studied. The amounts of TILs and TLSs were measured histopathologically using hematoxylin and eosin–stained slides. The HEV densities and TIL subpopulations were measured by immunohistochemistry for MECA79, CD3, CD8, and CD20. CXCL13mRNA expression levels using a NanoString assay (NanoString Technologies). Results The mean number of HEVs in pre-NAC biopsies was 12 (range, 0 to 72). The amounts of TILs and TLSs, HEV density, and CXCL13 expression showed robust correlations with each other. A lower pre-NAC clinical T stage, higher TIL and TLS levels, a higher HEV density, CD20-positive cell density, and CXCL13 expression were significant predictors of a pathologic complete response (pCR). Higher CD8-positive cell density and levels of CXCL13 expression were significantly associated with a better disease-free survival rate. Conclusion MECA79-positive HEV density in pre-NAC biopsies is an objective and quantitative surrogate marker of TLS and might be a valuable tool for predicting pCR of TNBC in routine pathology practice. PMID:27488875

Immunohistochemical Assessment of HER3 Expression in Odontogenic Cysts

PubMed Central

Honarmand, Marieh; Saravani, Shirin; Kamyab, Nazanin; Jahantigh, Mehdi; Torabi Parizi, Molouk

2015-01-01

Background: It has been demonstrated that HER3 plays an important role in some human cancers and the HER3 expression is associated with worse survival in solid tumors. Objectives: This study was conducted to compare HER3 expression in epithelial lining of radicular cysts (RCs), dentigerous cysts (DCs) and odontogenic keratocysts (OKCs). Materials and Methods: This was a descriptive-analytical study, which assessed all 57 paraffin blocks of RCs, DCs and OKCs (21 RCs, 16 DCs, 20 OKC) from pathological archive of Dentistry College of Zahedan, Iran. The HER3 expression in cytoplasm and membrane was examined by immunohistochemical method. The data collected was analyzed using SPSS16 by ANOVA and Chi-square. P < 0.05 was considered as statistically significant. Results: The HER3 expression had positive results in 52.4% of OKC, 50% of DC and only 20% of RC samples. There was a significant difference between HER3 expression in OKCs and RCs. Conclusions: The HER3 expression in developmental odontogenic cysts was higher than that in inflammatory odontogenic cysts. The higher rate of HER3 expression in OKC may justify inherent growth potential, stimulation-independent proliferation capability, invasive growth and high recurrence rate of the cyst accepted today as a tumor. PMID:26734469

The oncogenic gene fusion TMPRSS2: ERG is not a diagnostic or prognostic marker for ovarian cancer

PubMed Central

Huang, Lillian; Schauer, Isaiah G; Zhang, Jing; Mercado-Uribe, Imelda; Deavers, Michael T; Huang, Jiaoti; Liu, Jinsong

2011-01-01

TMPRSS2:ERG is a gene fusion resulting from the chromosomal rearrangement of the androgen-regulated TMPRSS2 gene and the ETS transcription factor ERG, leading to the over-expression of the oncogenic molecule ERG. This gene rearrangement has been found in approximately half of all prostate cancers and ERG overexpression is considered as a novel diagnostic marker for prostate carcinoma. However, little is known about the role of the TMPRSS2:ERG gene fusion in ovarian cancer. The purpose of this study was to test ERG expression in ovarian cancer and its potential as a diagnostic marker for ovarian carcinoma progression. A tissue microarray containing 180 ovarian cancer tissues of various pathological types and grades were examined by immunohistochemical analysis for expression of ERG. We also used 40 prostate carcinoma tissues and 40 normal tissues for comparison in parallel experiments. ERG-positive expression was detected in 40% of the prostate tumor cancer, as well as in internal positive control endothelial cells, confirming over-expression of ERG in prostate cancer at relatively the same rate observed by others. In contrast, all of the ovarian tumor patient tissues of varying histologic types were ERG-negative, despite some positivity in endothelial cells. These results suggest that the oncogenic gene fusion TMPRSS2:ERG does not occur in ovarian cancer relative to prostate cancer. Therefore, development of ERG expression profile would not be a useful diagnostic or prognostic marker for ovarian cancer patient screening. PMID:22076164

The oncogenic gene fusion TMPRSS2: ERG is not a diagnostic or prognostic marker for ovarian cancer.

PubMed

Huang, Lillian; Schauer, Isaiah G; Zhang, Jing; Mercado-Uribe, Imelda; Deavers, Michael T; Huang, Jiaoti; Liu, Jinsong

2011-01-01

TMPRSS2:ERG is a gene fusion resulting from the chromosomal rearrangement of the androgen-regulated TMPRSS2 gene and the ETS transcription factor ERG, leading to the over-expression of the oncogenic molecule ERG. This gene rearrangement has been found in approximately half of all prostate cancers and ERG overexpression is considered as a novel diagnostic marker for prostate carcinoma. However, little is known about the role of the TMPRSS2:ERG gene fusion in ovarian cancer. The purpose of this study was to test ERG expression in ovarian cancer and its potential as a diagnostic marker for ovarian carcinoma progression. A tissue microarray containing 180 ovarian cancer tissues of various pathological types and grades were examined by immunohistochemical analysis for expression of ERG. We also used 40 prostate carcinoma tissues and 40 normal tissues for comparison in parallel experiments. ERG-positive expression was detected in 40% of the prostate tumor cancer, as well as in internal positive control endothelial cells, confirming over-expression of ERG in prostate cancer at relatively the same rate observed by others. In contrast, all of the ovarian tumor patient tissues of varying histologic types were ERG-negative, despite some positivity in endothelial cells. These results suggest that the oncogenic gene fusion TMPRSS2:ERG does not occur in ovarian cancer relative to prostate cancer. Therefore, development of ERG expression profile would not be a useful diagnostic or prognostic marker for ovarian cancer patient screening.

Clinicopathologic implication of hepatic progenitor cell marker expression in hepatoblastoma.

PubMed

Yun, Woong Jae; Shin, Eun; Lee, Kyoungbun; Jung, Hae Yoen; Kim, Soo Hee; Park, Young-Nyun; Yu, Eunsil; Jang, Ja-June

2013-09-01

Hepatic progenitor cells (HPCs) are thought to play a role in hepatoblastoma, as hepatoblastomas are characterized by an immature histology and a wide variety of cell lineages. We aimed to investigate the extent of expression of HPCs marker and its clinical implication in hepatoblastoma. We collected 61 hepatoblastomas and 9 childhood hepatocellular carcinomas (HCCs) and performed immunohistochemistry for HPC markers, including cytokeratin 19 (CK19), octamer-binding transcription factor 3/4 (Oct-3/4), epithelial cell adhesion molecule (EpCAM), and delta-like 1 homolog (DLK1). Of the hepatoblastoma samples, 27/61 (44.3%), 21/61 (34.4%), 51/61 (83.6%) and 56/61 (91.8%) exhibited positivity for CK19, Oct-3/4, EpCAM and DLK-1, respectively. For HCCs, the rates of expression were 22.2% (CK19), 77.8% (EpCAM) and 77.8% (DLK-1). Oct-3/4 was not expressed in HCC cells. Hepatoblastomas with a poorly differentiated epithelial component had a higher incidence of CK19 and Oct-3/4 expression than those with a well differentiated epithelial component (p=0.005 and 0.037, respectively). Higher disease stage of hepatoblastoma was correlated with CK19 expression (p=0.043). Oct-3/4-positive hepatoblastomas were associated with short disease-free survival (p=0.035). Both hepatoblastomas and childhood HCCs, therefore, exhibit characteristics of HPCs, and the poor prognosis of patients with Oct-3/4-positive hepatoblastoma suggests that stem-like properties affect hepatoblastoma pathogenicity. Copyright © 2013 Elsevier GmbH. All rights reserved.

[Relationship between assertiveness including consideration for others and adjustment in children].

PubMed

Eguchi, Megumi; Hamaguchi, Yoshikazu

2012-06-01

The relationship between assertiveness and internal and external adjustment was investigated. Elementary school children in grades four to six (n=207) and their classroom teachers (n=8) participated in the study. Internal and external adjustments were measured by using self-ratings, and self- and other- ratings respectively. The children responded to a questionnaires inquiring about assertiveness that included two components of assessment: "self expression" and "consideration for others". Then, the children were divided into 4 groups according to their scores on these two components of assertiveness. The results indicated that children scoring high on both components of assertiveness had higher self-rating scores than those scoring low on both components. Moreover, children that scored high on "consideration for others" tended to have high external adjustment. Also, boys that scored low on "self expression" had lower external adjustment as indicated by the negative ratings of teachers. Furthermore, girls that scored high on "consideration for others" had high external adjustment as indicated by positive ratings of teachers and same-sexed classmates.

Preclinical Assessment of the Proliferation Capacity of Gingival and Periodontal Ligament Stem Cells from Diabetic Patients.

PubMed

Assem, Mostafa; Kamal, Samia; Sabry, Dina; Soliman, Nadia; Aly, Riham M

2018-02-15

Stem cells have recently received great interest as potential therapeutics alternative for a variety of diseases. The oral and maxillofacial region, in particular, encompasses a variety of distinctive mesenchymal (MSC) populations and is characterized by a potent multilineage differentiation capacity. In this report, we aimed to investigate the effect of diabetes on the proliferation potential of stem cells isolated from controlled diabetic patients (type 2) and healthy individuals. The proliferation rate of gingival and periodontal derived stem cells isolated from diabetic & healthy individuals were compared using MTT Assay. Expression levels of Survivin in isolated stem cells from all groups were measured by qRt - PCR. There was a significantly positive correlation between proliferation rate and expression of Survivin in all groups which sheds light on the importance of Survivin as a reliable indicator of proliferation. The expression of Survivin further confirmed the proliferation results from MTT Assay where the expression of stem cells from non - diabetic individuals was higher than diabetic patients. Taking together all the results, it could be concluded that PDLSC and GSC are promising candidates for autologous regenerative therapy due to their ease of accessibility in addition to their high proliferative rates.

Effectiveness of adaptive pretend play on affective expression and imagination of children with cerebral palsy.

PubMed

Hsieh, Hsieh-Chun

2012-01-01

Children with cerebral palsy (CP) have difficulty participating in role-pretending activities. The concept of adaptive play makes play accessible by modifying play materials for different needs or treatment goals for children with CP. This study examines the affective expressions and imagination in children with CP as a function of ordinary versus adaptive pretend play. The Affect in Play Scale-Brief Rating measured the affective expression and imagination for 29 children with CP and 29 typically developing children (mean age=7.34 years). Two groups of children were observed while playing with a standard set of ordinary toys for ten times and with a standard procedure of adaptive pretend play for ten times. The results show significantly different affective expressions and imagination between the two groups. Typically developing children displayed much more affective expression and imagination. However, a more positive influence of affective expression and imagination occurred in children with CP than in typically developing children. In repeated measures analysis, the frequency of positive affective expression and imagination of children with CP was higher when pretending with adaptive toys. Adaptive pretend play can promote more role-pretending behaviors and a sense of environmental control during the manipulating process for children with CP. Copyright © 2012 Elsevier Ltd. All rights reserved.

Expression of HSP27 in Hepatocellular Carcinoma.

PubMed

Eto, Daimei; Hisaka, Toru; Horiuchi, Hiroyuki; Uchida, Shinji; Ishikawa, Hiroto; Kawashima, Yusuke; Kinugasa, Tetsushi; Nakashima, Osamu; Yano, Hirohisa; Okuda, Koji; Akagi, Yoshito

2016-07-01

Heat-shock protein 27 (HSP27), a low molecular weight stress protein, is recognized as a molecular chaperone. The expression of HSP27 has been detected in some human tumors and while HSP27 is phosphorylated as a reresponse to stress, the function of phosphorylated HSP27 (p-HSP27) is not known. The aim of this study was to investigate what kind of effect expression of HSP27 and p-HSP27 in HCC has on clinicopathological characteristics and prognosis. An immunohistochemical study for HSP27 and p-HSP27 was performed on 194 resected HCC cases. We analyzed the correlation of HSP27 expression with various parameters statistically. There was no correlation between expression of HSP27 and the clinicopathological characteristics and prognosis from the analysis of 194 cases. From the analysis of the hepatitis C virus (HCV)-positive group of 142 cases, those that were p-HSP27-positive had a larger tumor diameter and the portal vein invasion rate was high. The expression of total HSP27 may serve as a new, clinically useful marker of HCC. In addition, the present study suggests that the expression of phosphorylated HSP27 is useful in the screening and grading of HCC occurring in the setting of HCV. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Gene expression information improves reliability of receptor status in breast cancer patients

PubMed Central

Kenn, Michael; Schlangen, Karin; Castillo-Tong, Dan Cacsire; Singer, Christian F.; Cibena, Michael; Koelbl, Heinz; Schreiner, Wolfgang

2017-01-01

Immunohistochemical (IHC) determination of receptor status in breast cancer patients is frequently inaccurate. Since it directs the choice of systemic therapy, it is essential to increase its reliability. We increase the validity of IHC receptor expression by additionally considering gene expression (GE) measurements. Crisp therapeutic decisions are based on IHC estimates, even if they are borderline reliable. We further improve decision quality by a responsibility function, defining a critical domain for gene expression. Refined normalization is devised to file any newly diagnosed patient into existing data bases. Our approach renders receptor estimates more reliable by identifying patients with questionable receptor status. The approach is also more efficient since the rate of conclusive samples is increased. We have curated and evaluated gene expression data, together with clinical information, from 2880 breast cancer patients. Combining IHC with gene expression information yields a method more reliable and also more efficient as compared to common practice up to now. Several types of possibly suboptimal treatment allocations, based on IHC receptor status alone, are enumerated. A ‘therapy allocation check’ identifies patients possibly miss-classified. Estrogen: false negative 8%, false positive 6%. Progesterone: false negative 14%, false positive 11%. HER2: false negative 2%, false positive 50%. Possible implications are discussed. We propose an ‘expression look-up-plot’, allowing for a significant potential to improve the quality of precision medicine. Methods are developed and exemplified here for breast cancer patients, but they may readily be transferred to diagnostic data relevant for therapeutic decisions in other fields of oncology. PMID:29100391

Construction of a novel multi-gene assay (42-gene classifier) for prediction of late recurrence in ER-positive breast cancer patients.

PubMed

Tsunashima, Ryo; Naoi, Yasuto; Shimazu, Kenzo; Kagara, Naofumi; Shimoda, Masashi; Tanei, Tomonori; Miyake, Tomohiro; Kim, Seung Jin; Noguchi, Shinzaburo

2018-05-04

Prediction models for late (> 5 years) recurrence in ER-positive breast cancer need to be developed for the accurate selection of patients for extended hormonal therapy. We attempted to develop such a prediction model focusing on the differences in gene expression between breast cancers with early and late recurrence. For the training set, 779 ER-positive breast cancers treated with tamoxifen alone for 5 years were selected from the databases (GSE6532, GSE12093, GSE17705, and GSE26971). For the validation set, 221 ER-positive breast cancers treated with adjuvant hormonal therapy for 5 years with or without chemotherapy at our hospital were included. Gene expression was assayed by DNA microarray analysis (Affymetrix U133 plus 2.0). With the 42 genes differentially expressed in early and late recurrence breast cancers in the training set, a prediction model (42GC) for late recurrence was constructed. The patients classified by 42GC into the late recurrence-like group showed a significantly (P = 0.006) higher late recurrence rate as expected but a significantly (P = 1.62 × E-13) lower rate for early recurrence than non-late recurrence-like group. These observations were confirmed for the validation set, i.e., P = 0.020 for late recurrence and P = 5.70 × E-5 for early recurrence. We developed a unique prediction model (42GC) for late recurrence by focusing on the biological differences between breast cancers with early and late recurrence. Interestingly, patients in the late recurrence-like group by 42GC were at low risk for early recurrence.

Increased positive versus negative affective perception and memory in healthy volunteers following selective serotonin and norepinephrine reuptake inhibition.

PubMed

Harmer, Catherine J; Shelley, Nicholas C; Cowen, Philip J; Goodwin, Guy M

2004-07-01

Antidepressants that inhibit the reuptake of serotonin (SSRIs) or norepinephrine (SNRIs) are effective in the treatment of disorders such as depression and anxiety. Cognitive psychological theories emphasize the importance of correcting negative biases of information processing in the nonpharmacological treatment of these disorders, but it is not known whether antidepressant drugs can directly modulate the neural processing of affective information. The present study therefore assessed the actions of repeated antidepressant administration on perception and memory for positive and negative emotional information in healthy volunteers. Forty-two male and female volunteers were randomly assigned to 7 days of double-blind intervention with the SSRI citalopram (20 mg/day), the SNRI reboxetine (8 mg/day), or placebo. On the final day, facial expression recognition, emotion-potentiated startle response, and memory for affect-laden words were assessed. Questionnaires monitoring mood, hostility, and anxiety were given before and after treatment. In the facial expression recognition task, citalopram and reboxetine reduced the identification of the negative facial expressions of anger and fear. Citalopram also abolished the increased startle response found in the context of negative affective images. Both antidepressants increased the relative recall of positive (versus negative) emotional material. These changes in emotional processing occurred in the absence of significant differences in ratings of mood and anxiety. However, reboxetine decreased subjective ratings of hostility and elevated energy. Short-term administration of two different antidepressant types had similar effects on emotion-related tasks in healthy volunteers, reducing the processing of negative relative to positive emotional material. Such effects of antidepressants may ameliorate the negative biases in information processing that characterize mood and anxiety disorders. They also suggest a mechanism of action potentially compatible with cognitive theories of anxiety and depression.

Emotional Processing of Infants Displays in Eating Disorders

PubMed Central

Cardi, Valentina; Corfield, Freya; Leppanen, Jenni; Rhind, Charlotte; Deriziotis, Stephanie; Hadjimichalis, Alexandra; Hibbs, Rebecca; Micali, Nadia; Treasure, Janet

2014-01-01

Aim The aim of this study is to examine emotional processing of infant displays in people with Eating Disorders (EDs). Background Social and emotional factors are implicated as causal and maintaining factors in EDs. Difficulties in emotional regulation have been mainly studied in relation to adult interactions, with less interest given to interactions with infants. Method A sample of 138 women were recruited, of which 49 suffered from Anorexia Nervosa (AN), 16 from Bulimia Nervosa (BN), and 73 were healthy controls (HCs). Attentional responses to happy and sad infant faces were tested with the visual probe detection task. Emotional identification of, and reactivity to, infant displays were measured using self-report measures. Facial expressions to video clips depicting sad, happy and frustrated infants were also recorded. Results No significant differences between groups were observed in the attentional response to infant photographs. However, there was a trend for patients to disengage from happy faces. People with EDs also reported lower positive ratings of happy infant displays and greater subjective negative reactions to sad infants. Finally, patients showed a significantly lower production of facial expressions, especially in response to the happy infant video clip. Insecure attachment was negatively correlated with positive facial expressions displayed in response to the happy infant and positively correlated with the intensity of negative emotions experienced in response to the sad infant video clip. Conclusion People with EDs do not have marked abnormalities in their attentional processing of infant emotional faces. However, they do have a reduction in facial affect particularly in response to happy infants. Also, they report greater negative reactions to sadness, and rate positive emotions less intensively than HCs. This pattern of emotional responsivity suggests abnormalities in social reward sensitivity and might indicate new treatment targets. PMID:25463051

Effect of Temperature on Synthetic Positive and Negative Feedback Gene Networks

NASA Astrophysics Data System (ADS)

Charlebois, Daniel A.; Marshall, Sylvia; Balazsi, Gabor

Synthetic biological systems are built and tested under well controlled laboratory conditions. How altering the environment, such as the ambient temperature affects their function is not well understood. To address this question for synthetic gene networks with positive and negative feedback, we used mathematical modeling coupled with experiments in the budding yeast Saccharomyces cerevisiae. We found that cellular growth rates and gene expression dose responses change significantly at temperatures above and below the physiological optimum for yeast. Gene expression distributions for the negative feedback-based circuit changed from unimodal to bimodal at high temperature, while the bifurcation point of the positive feedback circuit shifted up with temperature. These results demonstrate that synthetic gene network function is context-dependent. Temperature effects should thus be tested and incorporated into their design and validation for real-world applications. NSERC Postdoctoral Fellowship (Grant No. PDF-453977-2014).

Efficient search, mapping, and optimization of multi-protein genetic systems in diverse bacteria

PubMed Central

Farasat, Iman; Kushwaha, Manish; Collens, Jason; Easterbrook, Michael; Guido, Matthew; Salis, Howard M

2014-01-01

Developing predictive models of multi-protein genetic systems to understand and optimize their behavior remains a combinatorial challenge, particularly when measurement throughput is limited. We developed a computational approach to build predictive models and identify optimal sequences and expression levels, while circumventing combinatorial explosion. Maximally informative genetic system variants were first designed by the RBS Library Calculator, an algorithm to design sequences for efficiently searching a multi-protein expression space across a > 10,000-fold range with tailored search parameters and well-predicted translation rates. We validated the algorithm's predictions by characterizing 646 genetic system variants, encoded in plasmids and genomes, expressed in six gram-positive and gram-negative bacterial hosts. We then combined the search algorithm with system-level kinetic modeling, requiring the construction and characterization of 73 variants to build a sequence-expression-activity map (SEAMAP) for a biosynthesis pathway. Using model predictions, we designed and characterized 47 additional pathway variants to navigate its activity space, find optimal expression regions with desired activity response curves, and relieve rate-limiting steps in metabolism. Creating sequence-expression-activity maps accelerates the optimization of many protein systems and allows previous measurements to quantitatively inform future designs. PMID:24952589

Empathic Responses to Mother’s Emotions Predict Internalizing Problems in Children of Depressed Mothers

PubMed Central

Tully, Erin C.; Donohue, Meghan Rose

2016-01-01

Recent theories posit that empathy, typically an adaptive characteristic, may be associated with internalizing problems when children are chronically exposed to mother’s depression. We tested this postulation in a sample of children (N=82, Mage=5 years). Children witnessed their mothers express sadness, anger, and happiness during a simulated phone conversation, and researchers rated children’s negative affective empathy, positive affective empathy, and information-seeking (cognitive empathy) in response to their mother’s emotions. The chronicity of mother's depression during the child’s lifetime moderated associations between children’s empathy and internalizing problems. As predicted, all three empathy measures were related to greater mother-rated internalizing problems in children of chronically (i.e., 2–3 years) depressed mothers. Greater positive empathy was related to lower internalizing problems in children of nondepressed mothers. Positive empathy may contribute to adaptive processes when mothers are not depressed, and positive, negative, and cognitive empathy may contribute to maladaptive processes when mothers are chronically depressed. PMID:27262565

Service without a smile: comparing the consequences of neutral and positive display rules.

PubMed

Trougakos, John P; Jackson, Christine L; Beal, Daniel J

2011-03-01

We used an experimental design to examine the intrapersonal and interpersonal processes through which neutral display rules, compared to positive display rules, influence objective task performance of poll workers and ratings provided by survey respondents of the poll workers. Student participants (N = 140) were trained to adhere to 1 of the 2 display rule conditions while delivering opinion surveys to potential patrons of an organization during a 40-min period. Results showed that, compared to positive display rules, neutral display rules resulted in less task persistence and greater avoidance behavior. These effects were mediated through a greater use of expression suppression. In addition, neutral display rules resulted in less positive respondent mood, which accounted for lower ratings of service quality and of overall favorability attitudes toward the sponsoring organization. The importance and ubiquity of neutral display rules are discussed, given the potential for positive and negative consequences at work. PsycINFO Database Record (c) 2011 APA, all rights reserved.

Asthma-Related Immune Responses in Youth With Asthma: Associations With Maternal Responsiveness and Expressions of Positive and Negative Affect in Daily Life

PubMed Central

Tobin, Erin T.; Kane, Heidi S.; Saleh, Daniel J.; Wildman, Derek E.; Breen, Elizabeth Crabb; Secord, Elizabeth; Slatcher, Richard B.

2015-01-01

Objective Stressful family environments early in life have negative effects on physical health. However, less is known about the health effects of positive aspects of families. We examined the associations between maternal responsiveness and immune markers among youth with asthma and identified youth expressions of positive affect as a potential mechanism of these associations. Methods Forty-three youths with asthma (26 males; aged 10-17) wore the Electronically Activated Recorder (EAR) for four days to assess maternal responsiveness and youth expressions of affect from audio-recordings of daily life. Trained coders rated EAR sound files for expressions of maternal responsiveness and affect displayed by the youth. Peripheral blood mononuclear cells were isolated, cultured, and assayed to determine stimulated levels of interleukin(IL)-5, IL-13, and interferon(IFN)- γ. Results Greater maternal responsiveness was associated with decreased stimulated production of IL-5 (r = −.38, p = .012) and IL-13 (r = −.33, p = .031). Greater total positive affect in youth was linked with decreased stimulated production of IL-5 (r = −.46, p = .002) and IL-13 (r = −.37, p = .014). Total negative affect among youth was unrelated to immune responses. There was a significant indirect effect of maternal responsiveness via positive affect in youth on lower levels of IL-5 (95% CI = −3.41, −.03) and IL-13 (95% CI = −2.34, −.01) when adjusting for caregiver-youth conflict and negative affect among youth. Conclusions These results indicate the importance of positive family interactions for youth and provide preliminary evidence for a mechanism through which parenting can influence immune responses in youths with asthma. PMID:26407226

Asthma-Related Immune Responses in Youth With Asthma: Associations With Maternal Responsiveness and Expressions of Positive and Negative Affect in Daily Life.

PubMed

Tobin, Erin T; Kane, Heidi S; Saleh, Daniel J; Wildman, Derek E; Breen, Elizabeth Crabb; Secord, Elizabeth; Slatcher, Richard B

2015-10-01

Stressful family environments early in life have negative effects on physical health. However, less is known about the health effects of positive aspects of families. We examined the associations between maternal responsiveness and immune markers among youth with asthma and identified youth expressions of positive affect as a potential mechanism of these associations. Forty-three youths with asthma (26 boys; aged 10-17 years) wore the Electronically Activated Recorder for 4 days to assess maternal responsiveness and youth expressions of affect from audio-recordings of daily life. Trained coders rated Electronically Activated Recorder sound files for expressions of maternal responsiveness and affect displayed by the youth. Peripheral blood mononuclear cells were isolated, cultured, and assayed to determine stimulated levels of interleukin (IL)-5, IL-13, and interferon-γ. Greater maternal responsiveness was associated with decreased stimulated production of IL-5 (r = -0.38, p = .012) and IL-13 (r = -0.33, p = .031). Greater total positive affect in youth was linked to decreased stimulated production of IL-5 (r = -0.46, p = .002) and IL-13 (r = -0.37, p = .014). Total negative affect among youth was unrelated to immune responses. There was a significant indirect effect of maternal responsiveness via positive affect in youth on lower levels of IL-5 (95% confidence interval = -3.41 to -0.03) and IL-13 (95% confidence interval = -2.34 to -0.01) when adjusting for caregiver-youth conflict and negative affect among youth. These results indicate the importance of positive family interactions for youth and provide preliminary evidence for a mechanism through which parenting can influence immune responses in youth with asthma.

Position Matters: Network Centrality Considerably Impacts Rates of Protein Evolution in the Human Protein–Protein Interaction Network

PubMed Central

Feyertag, Felix; Chakraborty, Sandip

2017-01-01

Abstract The proteins of any organism evolve at disparate rates. A long list of factors affecting rates of protein evolution have been identified. However, the relative importance of each factor in determining rates of protein evolution remains unresolved. The prevailing view is that evolutionary rates are dominantly determined by gene expression, and that other factors such as network centrality have only a marginal effect, if any. However, this view is largely based on analyses in yeasts, and accurately measuring the importance of the determinants of rates of protein evolution is complicated by the fact that the different factors are often correlated with each other, and by the relatively poor quality of available functional genomics data sets. Here, we use correlation, partial correlation and principal component regression analyses to measure the contributions of several factors to the variability of the rates of evolution of human proteins. For this purpose, we analyzed the entire human protein–protein interaction data set and the human signal transduction network—a network data set of exceptionally high quality, obtained by manual curation, which is expected to be virtually free from false positives. In contrast with the prevailing view, we observe that network centrality (measured as the number of physical and nonphysical interactions, betweenness, and closeness) has a considerable impact on rates of protein evolution. Surprisingly, the impact of centrality on rates of protein evolution seems to be comparable, or even superior according to some analyses, to that of gene expression. Our observations seem to be independent of potentially confounding factors and from the limitations (biases and errors) of interactomic data sets. PMID:28854629

Position Matters: Network Centrality Considerably Impacts Rates of Protein Evolution in the Human Protein-Protein Interaction Network.

PubMed

Alvarez-Ponce, David; Feyertag, Felix; Chakraborty, Sandip

2017-06-01

The proteins of any organism evolve at disparate rates. A long list of factors affecting rates of protein evolution have been identified. However, the relative importance of each factor in determining rates of protein evolution remains unresolved. The prevailing view is that evolutionary rates are dominantly determined by gene expression, and that other factors such as network centrality have only a marginal effect, if any. However, this view is largely based on analyses in yeasts, and accurately measuring the importance of the determinants of rates of protein evolution is complicated by the fact that the different factors are often correlated with each other, and by the relatively poor quality of available functional genomics data sets. Here, we use correlation, partial correlation and principal component regression analyses to measure the contributions of several factors to the variability of the rates of evolution of human proteins. For this purpose, we analyzed the entire human protein-protein interaction data set and the human signal transduction network-a network data set of exceptionally high quality, obtained by manual curation, which is expected to be virtually free from false positives. In contrast with the prevailing view, we observe that network centrality (measured as the number of physical and nonphysical interactions, betweenness, and closeness) has a considerable impact on rates of protein evolution. Surprisingly, the impact of centrality on rates of protein evolution seems to be comparable, or even superior according to some analyses, to that of gene expression. Our observations seem to be independent of potentially confounding factors and from the limitations (biases and errors) of interactomic data sets. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Expression Levels of KMT2C and SLC20A1 Identified by Information-theoretical Analysis Are Powerful Prognostic Biomarkers in Estrogen Receptor-positive Breast Cancer.

PubMed

Sato, Keiko; Akimoto, Kazunori

2017-06-01

In general, it has been considered that estrogen receptor-positive (ER + ) breast cancer has a good prognosis and is responsive to endocrine therapy. However, one third of patients with ER + breast cancer exhibit endocrine therapy resistance, and many patients develop recurrence and die 5 to 10 years after diagnosis. In ER +  breast cancer, a major problem is to distinguish those patients most likely to develop recurrence or metastatic disease within 10 years after diagnosis from those with a sufficiently good prognosis. We downloaded the messenger RNA expression data and the clinical information for 401 patients with ER +  breast cancer from the cBioPortal for Cancer Genomics. An information-theoretical approach was used to identify the prognostic factors for survival in patients with ER + breast cancer and to classify those patients according to the prognostic factors. The information-theoretical approach contributed to the identification of KMT2C and SLC20A1 as prognostic biomarkers in ER + breast cancer. We found that low KMT2C expression was associated with a poor outcome and high SLC20A1 expression was associated with a poor outcome. Both levels of KMT2C and SLC20A1 expression were significantly and strongly associated with the differentiation of survival. The 10-year survival rate for ER + patients with low KMT2C and high SLC20A1 expression was 0%. In contrast, for ER + patients with high KMT2C and low SLC20A1 expression, the 10-year survival rate was 86.78%. Our results strongly suggest that clinical examination of the expression of both KMT2C and SLC20A1 in ER + breast cancer will be very useful for the determination of prognosis and therapy. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Mathematical model of a smoldering log.

Treesearch

Fernando de Souza Costa; David Sandberg

2004-01-01

A mathematical model is developed describing the natural smoldering of logs. It is considered the steady one dimensional propagation of infinitesimally thin fronts of drying, pyrolysis, and char oxidation in a horizontal semi-infinite log. Expressions for the burn rates, distribution profiles of temperature, and positions of the drying, pyrolysis, and smoldering fronts...

Mucin (MUC) expression in EUS-FNA specimens is a useful prognostic factor in pancreatic ductal adenocarcinoma

PubMed Central

Higashi, Michiyo; Yokoyama, Seiya; Yamamoto, Takafumi; Goto, Yuko; Kitazono, Ikumi; Hiraki, Tsubasa; Taguchi, Hiroki; Hashimoto, Shinichi; Fukukura, Yoshihiko; Koriyama, Chihaya; Mataki, Yuko; Maemura, Kosei; Shinchi, Hiroyuki; Jain, Maneesh; Batra, Surinder K.; Yonezawa, Suguru

2015-01-01

Objectives The aim of this study was to further examine the utility of mucin expression profiles as prognostic factors in PDAC. Methods Mucin (MUC) expression was examined by immunohistochemistry (IHC) analysis in endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) specimens obtained from 114 patients with PDAC. The rate of expression of each mucin was compared with clinicopathologic features. Results The expression rates of mucins in cancer lesions were MUC1, 87.7%; MUC2, 0.8%; MUC4, 93.0%; MUC5AC, 78.9%; MUC6, 24.6%; and MUC16, 67.5%. MUC1 and MUC4 were positive and MUC2 was negative in most PDACs. Patients with advanced stage of PDAC with MUC5AC expression had a significantly better outcome than those who were MUC5AC-negative (P=0.002).With increasing clinical stage, total MUC6 expression decreased (P for trend=0.001) and MUC16 cytoplasmic expression increased (P for trend=0.02). The prognosis of patients with MUC16 cytoplasmic expression was significantly poorer than those without this expression. Multivariate survival analysis revealed that MUC16 cytoplasmic expression was a significant independent predictor of a poor prognosis after adjusting for the effects of other prognostic factors (P=0.002). Conclusion Mucin expression profiles in EUS-FNA specimens have excellent diagnostic utility and are useful predictors of outcome in patients with PDAC. PMID:25906442

Factors Associated with Patient Reports of Positive Physician Relational Communication

PubMed Central

Shay, L. Aubree; Dumenci, Levent; Siminoff, Laura A.; Flocke, Susan A.; Lafata, Jennifer Elston

2012-01-01

Objective To evaluate the patient, physician, and visit-related factors associated with patient ratings of positive physician relational communication. Methods Pre- and post-visit surveys were conducted with 485 patients attending a routine periodic health exam with one of 64 participating physicians. The audio-recorded visits were coded for elements of patient-physician communication including assertive responses, partnership building, question asking, supportive talk, and expressions of concern. Results Patient reports of positive physician relational communication were associated with patient perceptions of how well the physician understood the patient’s health care preferences and values, a patient-physician interaction outside of the exam room, and physician-prompted patient expressions of concern. Conclusion In addition to a patient’s perception of their relationship with their physician going into the visit, relatively simple acts like extending the interaction beyond the exam room and ensuring that patients feel invited to express concerns they may have during the visit may influence patient perceptions of physician relational communication. Practice Implications This study offers preliminary support for the idea that relational communication and its associated benefits may be fostered through simple physician-driven acts such as interacting with patients outside of the exam room and encouraging patients to express concerns within the visit. PMID:22554386

Common Co-activation of AXL and CDCP1 in EGFR-mutation-positive Non-smallcell Lung Cancer Associated With Poor Prognosis.

PubMed

Karachaliou, Niki; Chaib, Imane; Cardona, Andres Felipe; Berenguer, Jordi; Bracht, Jillian Wilhelmina Paulina; Yang, Jie; Cai, Xueting; Wang, Zhigang; Hu, Chunping; Drozdowskyj, Ana; Servat, Carles Codony; Servat, Jordi Codony; Ito, Masaoki; Attili, Ilaria; Aldeguer, Erika; Capitan, Ana Gimenez; Rodriguez, July; Rojas, Leonardo; Viteri, Santiago; Molina-Vila, Miguel Angel; Ou, Sai-Hong Ignatius; Okada, Morihito; Mok, Tony S; Bivona, Trever G; Ono, Mayumi; Cui, Jean; Cajal, Santiago Ramón Y; Frias, Alex; Cao, Peng; Rosell, Rafael

2018-03-01

Epidermal growth factor receptor (EGFR)-mutation-positive non-smallcell lung cancer (NSCLC) is incurable, despite high rates of response to EGFR tyrosine kinase inhibitors (TKIs). We investigated receptor tyrosine kinases (RTKs), Src family kinases and focal adhesion kinase (FAK) as genetic modifiers of innate resistance in EGFR-mutation-positive NSCLC. We performed gene expression analysis in two cohorts (Cohort 1 and Cohort 2) of EGFR-mutation-positive NSCLC patients treated with EGFR TKI. We evaluated the efficacy of gefitinib or osimertinib with the Src/FAK/Janus kinase 2 (JAK2) inhibitor, TPX0005 in vitro and in vivo. In Cohort 1, CUB domain-containing protein-1 (CDCP1) was an independent negative prognostic factor for progression-free survival (hazard ratio of 1.79, p=0.0407) and overall survival (hazard ratio of 2.23, p=0.0192). A two-gene model based on AXL and CDCP1 expression was strongly associated with the clinical outcome to EGFR TKIs, in both cohorts of patients. Our preclinical experiments revealed that several RTKs and non-RTKs, were up-regulated at baseline or after treatment with gefitinib or osimertinib. TPX-0005 plus EGFR TKI suppressed expression and activation of RTKs and downstream signaling intermediates. Co-expression of CDCP1 and AXL is often observed in EGFR-mutation-positive tumors, limiting the efficacy of EGFR TKIs. Co-treatment with EGFR TKI and TPX-0005 warrants testing. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Gender Differences in the Social Cost of Affective Deviance.

PubMed

Brown, Christina M; Olkhov, Yevgeniy M; Bailey, Veronika S; Daniels, Emily R

2015-01-01

The current study tested whether men and women receive different degrees of social punishment for violating norms of emotional expression. Participants watched videos of male and female targets (whose reactions were pre-tested to be equivalent in expressivity and valence) viewing either a positive or negative slideshow, with their emotional reaction to the slideshow manipulated to be affectively congruent, affectively incongruent, or flat. Participants then rated the target on a number of social evaluation measures. Displaying an incongruent emotional expression, relative to a congruent one, harmed judgments of women more than men. Women are expected to be more emotionally expressive than men, making an incongruent expression more deviant for women. These results highlight the importance of social norms in construing another person's emotion displays, which can subsequently determine acceptance or rejection of that person.

Expression of M2-polarized macrophages is associated with poor prognosis for advanced epithelial ovarian cancer.

PubMed

Lan, Chunyan; Huang, Xin; Lin, Suxia; Huang, Huiqiang; Cai, Qichun; Wan, Ting; Lu, Jiabin; Liu, Jihong

2013-06-01

Macrophages are polarized into two functionally distinct forms, M1 and M2, in response to different microenvironment. Tumor-associated macrophages (TAMs) generally have M2 phenotype and promote tumor progression. Few studies to date have described the infiltration of M2-polarized macrophages in ovarian cancer. We used two macrophages markers, CD68 and CD163, to analyze the expression of TAMs and to clarify the relationship between the M2 form and survival in advanced ovarian cancer. Clinical data of 110 patients with stages III-IV epithelial ovarian cancer at Sun Yat-sen University Cancer Center between 1999 and 2007 were retrospectively reviewed. Immunohistochemical staining of CD68 and CD163 was performed. Correlations between macrophage density and patient survival were analyzed. Our data showed that no significant difference was observed in survival between patients in the high- and the low-CD68 expression groups. In contrast, the progression-free survival (PFS) rates (p = 0.003) and overall survival (OS) rates (p = 0.004) were significantly higher in the low-CD163 expression group than in the high-CD163 expression group, respectively. Similarly, we also observed significantly improved 3-year PFS (49.8% vs. 11.0%, p < 0.001) and OS (77.4% vs. 45.0%, p < 0.001) rates in patients in the low-CD163/CD68 ratio group when compared with the high-CD163/CD68 ratio group. Multivariate analysis identified the density of CD163-positive cells as well as the ratio of CD163/CD68 as negative predictors for PFS and OS, respectively. Our results show that the infiltration of CD163-positive M2 macrophages as well as activation of macrophages towards the M2 phenotype may contribute to poor survival in advanced ovarian cancer.

Characterization of patient-derived tumor xenografts (PDXs) as models for estrogen receptor positive (ER+HER2- and ER+HER2+) breast cancers.

PubMed

Kanaya, Noriko; Somlo, George; Wu, Jun; Frankel, Paul; Kai, Masaya; Liu, Xueli; Wu, Shang Victoria; Nguyen, Duc; Chan, Nymph; Hsieh, Meng-Yin; Kirschenbaum, Michele; Kruper, Laura; Vito, Courtney; Badie, Behnam; Yim, John H; Yuan, Yuan; Hurria, Arti; Peiguo, Chu; Mortimer, Joanne; Chen, Shiuan

2017-06-01

The research was to appraise the utility of the patient-derived tumor xenografts (PDXs) as models of estrogen receptor positive (ER+HER2- and ER+HER2+) breast cancers. We compared protein expression profiles by Reverse Phase Protein Array (RPPA) in tumors that resulted in PDXs compared to those that did not. Our overall PDX intake rate for ER+ breast cancer was 9% (9/97). The intake rate for ER+HER2+ tumors (3/16, 19%) was higher than for ER+HER2- tumors (6/81, 7%). Heat map analyses of RPPA data showed that ER+HER2- tumors were divided into 2 groups by luminal A/B signature [protein expression of ER, AR, Bcl-2, Bim (BCL2L11), GATA3 and INPP4b], and this expression signature was also associated with the rate of PDX intake. Cell survival pathways such as the PI3K/AKT signaling and RAS/ERK pathways were more activated in the specimens that could be established as PDX in both classes. Expression of the ER protein itself may have a bearing on the potential success of an ER+ PDX model. In addition, HER2 and its downstream protein expressions were up-regulated in the ER+HER2+ patient tumors that were successfully established as PDX models. Moreover, the comparison of RPPA data between original and PDX tumors suggested that the selection/adaptation process required to grow the tumors in mice is unavoidable for generation of ER+ PDX models, and we identified differences between patient tumor samples and paired PDX tumors. A better understanding of the biological characteristics of ER+PDX would be the key to using PDX models in assessing treatment strategies in a preclinical setting. Copyright © 2016 Elsevier Ltd. All rights reserved.

Decreased Apoptotic Rate of Alveolar Macrophages of Patients with Idiopathic Pulmonary Fibrosis

PubMed Central

Drakopanagiotakis, Fotios; Xifteri, Areti; Tsiambas, Evaggelos; Karameris, Andreas; Tsakanika, Konstantina; Karagiannidis, Napoleon; Mermigkis, Demetrios; Polychronopoulos, Vlasis; Bouros, Demosthenes

2012-01-01

Introduction. Increased apoptosis of epithelial cells and decreased apoptosis of myofibroblasts are involved in the pathogenesis of IPF. The apoptotic profile of alveolar macrophages (AMs) in IPF is unclear. Aim. To investigate whether AMs of patients with IPF exhibit a different apoptotic profile compared to normal subjects. Methods. We analyzed, by immunohistochemistry, the expression of the apoptotic markers fas, fas ligand , bcl-2, and bax in AM obtained from bronchoalveolar lavage fluid (BALF) of 20 newly diagnosed, treatment-naive IPF patients and of 16 controls. Apoptosis of AM was evaluated by Apoptag immunohistochemistry. IPF patients received either interferon-g and corticosteroids or azathioprine and corticosteroids for six months. Results. BALF AMs undergoing apoptosis were significantly less in IPF patients. No difference was found in the expression of fas or fas ligand, bcl-2 and bax between IPF and control group. No difference was found between the respiratory function parameters of the two treatment groups after six months. A positive correlation was found between the number of bcl-2 positive stained macrophages and DLCO after treatment. Conclusions. The decreased apoptotic rate of AM of patients with IPF is not associated with decreased expression of apoptosis mediators involved in the external or internal apoptotic pathway. PMID:22792456

Effects of environmental stress on mRNA expression levels of seven genes related to oxidative stress and growth in Atlantic salmon Salmo salar L. of farmed, hybrid and wild origin.

PubMed

Solberg, Monica F; Kvamme, Bjørn Olav; Nilsen, Frank; Glover, Kevin A

2012-12-05

Ten generations of domestication selection has caused farmed Atlantic salmon Salmo salar L. to deviate from wild salmon in a range of traits. Each year hundreds of thousands of farmed salmon escape into the wild. Thus, interbreeding between farmed escapees and wild conspecifics represents a significant threat to the genetic integrity of wild salmon populations. In a previous study we demonstrated how domestication has inadvertently selected for reduced responsiveness to stress in farmed salmon. To complement that study, we have evaluated the expression of seven stress-related genes in head kidney of salmon of farmed, hybrid and wild origin exposed to environmentally induced stress. In general, the crowding stressor used to induce environmental stress did not have a strong impact on mRNA expression levels of the seven genes, except for insulin-like growth factor-1 (IGF-1) that was downregulated in the stress treatment relative to the control treatment. mRNA expression levels of glutathione reductase (GR), Cu/Zn superoxide dismutase (Cu/Zn SOD), Mn superoxide dismutase (Mn SOD), glutathione peroxidase (GP) and IGF-1 were affected by genetic origin, thus expressed significantly different between the salmon of farmed, hybrid or wild origin. A positive relationship was detected between body size of wild salmon and mRNA expression level of the IGF-1 gene, in both environments. No such relationship was observed for the hybrid or farmed salmon. Farmed salmon in this study displayed significantly elevated mRNA levels of the IGF-1 gene relative to the wild salmon, in both treatments, while hybrids displayed a non additive pattern of inheritance. As IGF-1 mRNA levels are positively correlated to growth rate, the observed positive relationship between body size and IGF-1 mRNA levels detected in the wild but neither in the farmed nor the hybrid salmon, could indicate that growth selection has increased IGF-1 levels in farmed salmon to the extent that they may not be limiting growth rate.

Effects of environmental stress on mRNA expression levels of seven genes related to oxidative stress and growth in Atlantic salmon Salmo salar L. of farmed, hybrid and wild origin

PubMed Central

2012-01-01

Background Ten generations of domestication selection has caused farmed Atlantic salmon Salmo salar L. to deviate from wild salmon in a range of traits. Each year hundreds of thousands of farmed salmon escape into the wild. Thus, interbreeding between farmed escapees and wild conspecifics represents a significant threat to the genetic integrity of wild salmon populations. In a previous study we demonstrated how domestication has inadvertently selected for reduced responsiveness to stress in farmed salmon. To complement that study, we have evaluated the expression of seven stress-related genes in head kidney of salmon of farmed, hybrid and wild origin exposed to environmentally induced stress. Results In general, the crowding stressor used to induce environmental stress did not have a strong impact on mRNA expression levels of the seven genes, except for insulin-like growth factor-1 (IGF-1) that was downregulated in the stress treatment relative to the control treatment. mRNA expression levels of glutathione reductase (GR), Cu/Zn superoxide dismutase (Cu/Zn SOD), Mn superoxide dismutase (Mn SOD), glutathione peroxidase (GP) and IGF-1 were affected by genetic origin, thus expressed significantly different between the salmon of farmed, hybrid or wild origin. A positive relationship was detected between body size of wild salmon and mRNA expression level of the IGF-1 gene, in both environments. No such relationship was observed for the hybrid or farmed salmon. Conclusion Farmed salmon in this study displayed significantly elevated mRNA levels of the IGF-1 gene relative to the wild salmon, in both treatments, while hybrids displayed a non additive pattern of inheritance. As IGF-1 mRNA levels are positively correlated to growth rate, the observed positive relationship between body size and IGF-1 mRNA levels detected in the wild but neither in the farmed nor the hybrid salmon, could indicate that growth selection has increased IGF-1 levels in farmed salmon to the extent that they may not be limiting growth rate. PMID:23217180

blaOXA-23-like and blaTEM rather than blaOXA-51-like contributed to a high level of carbapenem resistance in Acinetobacter baumannii strains from a teaching hospital in Xi'an, China.

PubMed

Han, Lei; Lei, Jine; Xu, Jiru; Han, Shaoshan

2017-12-01

Acinetobacter baumannii is one of the major threats in clinical infections due to its antibiotic resistance ability. It shows increasing resistance to carbapenems, mainly due to β-lactamase mediated mechanisms. The aim of this study was to investigate carbapenem resistance (CR) profiles and analyze β-lactamases genes composition of clinical A. baumannii strains from a teaching hospital in Xi'an. The resistance patterns to imipenem and meropenem were checked for 51 clinical A. baumannii strains. The existence of 15 β-lactamases genes was detected by polymerase chain reaction (PCR), and the positive genes were sequenced. The correlation between PCR-positive genes and CR phenotype was analyzed using Chi-square test and contingency coefficient. The expressions of PCR-positive genes were investigated. Forty-five out of 51 strains were resistant to imipenem and meropenem. blaTEM, blaOXA-23-like, and blaOXA-51-like were positive among 15 β-lactamases genes, and TEM-1, OXA-23, and OXA-66/69 were their subtypes. TEM and OXA-23-like only showed up in CR isolates, with the occurrence rate of 91.1% and 97.8%, respectively, whereas OXA-51-like appeared in all strains. ISAba1 was present in the upstream of OXA-23-like, but absent from that of OXA-51-like in our strains. OXA-23-like had highest relationship with CR, followed by TEM, but OXA-51-like had no correlation. This was verified by RT-qPCR that the expression was positive for OXA-23 and TEM-1, but negative for OXA-66/-69. A high rate of CR A. baumannii was detected in this study. Coexistence of TEM, OXA-23-like, and OXA-51-like was the primary resistance profile. The expressions of OXA-23-like and TEM genes were closely related with CR, while OXA-51-like had no contribution to the CR phenotype.

Maternal attitudes towards home birth and their effect on birth outcomes in Iceland: A prospective cohort study.

PubMed

Halfdansdottir, Berglind; Olafsdottir, Olof A; Hildingsson, Ingegerd; Smarason, Alexander Kr; Sveinsdottir, Herdis

2016-03-01

to examine the relationship between attitudes towards home birth and birth outcomes, and whether women's attitudes towards birth and intervention affected this relationship. a prospective cohort study. the study was set in Iceland, a sparsely populated island with harsh terrain, 325,000 inhabitants, high fertility and home birth rates, and less than 5000 births a year. a convenience sample of women who attended antenatal care in Icelandic health care centres, participated in the Childbirth and Health Study in 2009-2011, and expressed consistent attitudes towards home birth (n=809). of the participants, 164 (20.3%) expressed positive attitudes towards choosing home birth and 645 (79.7%) expressed negative attitudes. Women who had a positive attitude towards home birth had significantly more positive attitudes towards birth and more negative attitudes towards intervention than did women who had a negative attitude towards home birth. Of the 340 self-reported low-risk women that answered questionnaires on birth outcomes, 78 (22.9%) had a positive attitude towards home birth and 262 (77.1%) had a negative attitude. Oxytocin augmentation (19.2% (n=15) versus 39.1% (n=100)), epidural analgesia (19.2% (n=15) versus 33.6% (n=88)), and neonatal intensive care unit admission rates (0.0% (n=0) versus 5.0% (n=13)) were significantly lower among women who had a positive attitude towards home birth. Women's attitudes towards birth and intervention affected the relationship between attitudes towards home birth and oxytocin augmentation or epidural analgesia. the beneficial effect of planned home birth on maternal outcome in Iceland may depend to some extent on women's attitudes towards birth and intervention. Efforts to de-stigmatise out-of-hospital birth and de-medicalize women's attitudes towards birth might increase women׳s use of health-appropriate birth services. Copyright © 2016 Elsevier Ltd. All rights reserved.

Keratins 17 and 19 expression as prognostic markers in oral squamous cell carcinoma.

PubMed

Coelho, B A; Peterle, G T; Santos, M; Agostini, L P; Maia, L L; Stur, E; Silva, C V M; Mendes, S O; Almança, C C J; Freitas, F V; Borçoi, A R; Archanjo, A B; Mercante, A M C; Nunes, F D; Carvalho, M B; Tajara, E H; Louro, I D; Silva-Conforti, A M A

2015-11-25

Five-year survival rates for oral squamous cell carcinoma (OSCC) are 30% and the mortality rate is 50%. Immunohistochemistry panels are used to evaluate proliferation, vascularization, apoptosis, HPV infection, and keratin expression, which are important markers of malignant progression. Keratins are a family of intermediate filaments predominantly expressed in epithelial cells and have an essential role in mechanical support and cytoskeleton formation, which is essential for the structural integrity and stability of the cell. In this study, we analyzed the expressions of keratins 17 and 19 (K17 and K19) by immunohistochemistry in tumoral and non-tumoral tissues from patients with OSCC. The results show that expression of these keratins is higher in tumor tissues compared to non-tumor tissues. Positive K17 expression correlates with lymph node metastasis and multivariate analysis confirmed this relationship, revealing a 6-fold increase in lymph node metastasis when K17 is expressed. We observed a correlation between K17 expression with disease-free survival and disease-specific death in patients who received surgery and radiotherapy. Multivariate analysis revealed that low expression of K17 was an independent marker for early disease relapse and disease-specific death in patients treated with surgery and radiotherapy, with an approximately 4-fold increased risk when compared to high K17 expression. Our results suggest a potential role for K17 and K19 expression profiles as tumor prognostic markers in OSCC patients.

L1CAM Expression is Related to Non-Endometrioid Histology, and Prognostic for Poor Outcome in Endometrioid Endometrial Carcinoma.

PubMed

Geels, Yvette P; Pijnenborg, Johanna M A; Gordon, Bart B M; Fogel, Mina; Altevogt, Peter; Masadah, Rina; Bulten, Johan; van Kempen, Léon C; Massuger, Leon F A G

2016-10-01

The majority of endometrial carcinomas are classified as Type I endometrioid endometrial carcinomas (EECs) and have a good prognosis. Type II non-endometrioid endometrial carcinomas (NEECs) have a significant worse outcome. Yet, 20 % of the EECs are associated with an unexplained poor outcome. The aim of this study was to determine if L1CAM expression, a recently reported biomarker for aggressive tumor behavior in endometrial carcinoma, was associated with clinicopathological features of EECs. A total of 103 patients diagnosed as EEC at the Radboud University Medical Centre, based on the pathology report were selected. L1CAM status of these tumors was determined, and histologic slides were reviewed by two expert pathologists. L1CAM-positivity was observed in 17 % (18/103). Review of the diagnostic slides revealed that 11 out of these 18 L1CAM-positive tumors (61 %) contained a serous- or mixed carcinoma component that was not initially mentioned in the pathology report. L1CAM-expression was associated with advanced age, poor tumor grade, and lymphovascular space invasion. A worse five year progression free survival rate was observed for patients with L1CAM-positive tumors (55.6 % for the L1CAM-positive group, compared to 83.3 % for the L1CAM-negative group P = 0.01). L1CAM expression carries prognostic value for histologically classified EEC and supports the identification of tumors with a NEEC component.

Parkin protein expression and its impact on survival of patients with advanced colorectal cancer.

PubMed

da Silva-Camargo, Claudia Caroline Veloso; Svoboda Baldin, Rosimeri Kuhl; Costacurta Polli, Nayanne Louise; Agostinho, Amanda Pereira; Olandosk, Marcia; de Noronha, Lúcia; Sotomaior, Vanessa Santos

2018-02-01

Features of colorectal cancer such as natural history, molecular, chromosomal, and epigenetic alterations have been well described. However, there is still a lack of accurate prognostic markers, which is evident by the lower overall survival rates of patients with advanced cancer. Although alterations in parkin protein expression have been described in colorectal cancer, the functional significance of this protein remains unknown. The present study aimed to investigate the involvement of parkin expression in colorectal adenocarcinoma development and progression by evaluating the association between its expression, clinicopathological parameters, and expression of known proteins involved in colorectal cancer. Tissue microarrays consisting of 73 tumor and 64 normal tissue samples were generated to examine parkin expression and localization by immunohistochemistry. A positive correlation of parkin and APC expression was observed in the superficial, intermediate, and profound regions of all cases (ρ = 0.37; P = 0.001). Parkin expression was also significantly associated with tumors in men ( P = 0.049), those of the mucinous subtype ( P = 0.028), and of advanced stage (III + IV, P = 0.041). In addition, increased parkin expression was observed in the invasive front tumor region ( P = 0.013). More importantly, a positive correlation was found between parkin expression and the overall survival of patients with advanced colorectal cancer ( P = 0.019). Multivariate analysis showed that parkin expression was independent of any of the clinicopathological parameters evaluated in relation to patient survival. These results suggest that parkin expression status can be used as a potential independent prognostic marker of survival in advanced colorectal cancer.

Expression of BTBD7 in primary salivary adenoid cystic carcinoma and correlation with Slug and prognosis.

PubMed

Yang, Liu; Wang, Tiejun; Zhang, Jun; Liu, Zhonghao; Wang, Xuxia

2016-06-24

BTB/POZ domain-containing protein 7 (BTBD7) is recognized as a regulatory gene that regulates epithelial cell dynamics and branching morphogenesis. It is also reported for regulating epithelial-mesenchymal transition (EMT) molecules and involved in the process of invasion and metastasis of lung cancer and hepatocellular carcinoma. Slug is a transcriptional factor of EMT which plays a crucial role in the process of primary salivary adenoid cystic carcinoma (SACC). However, the role of BTBD7 in SACC and the correlation with Slug have not been identified. This study investigated the expression of BTBD7 and correlation with Slug, as well as the prognostic significance of BTBD7 in SACC. The expression of BTBD7 and Slug were examined in ACC-LM and ACC-83 cell lines and immunohistochemically in paraffin embedded tissue specimens from 66 primary SACC patients. Statistical analyses were performed to evaluate the correlation between BTBD7 expression and Slug expression and the prognostic significance of BTBD7 expression. BTBD7 protein expression was initially verified in ACC-LM and ACC-83 cell lines. The positive rate of BTBD7 expression was 62.1% in SACC to 20% in normal salivary tissues comparatively. BTBD7 expression was significantly correlated with Slug expression in SACC (P< 0.05). Increased BTBD7 expression was significantly associated with the TNM stage, tissue typing, distant metastasis and patients' poor clinical outcome. Positive expression of BTBD7 in SACC could play an important role in the development of cancer and may serve as a favorable predictor for diagnosis and poor prognosis of patients.

Emotion Estimation Algorithm from Facial Image Analyses of e-Learning Users

NASA Astrophysics Data System (ADS)

Shigeta, Ayuko; Koike, Takeshi; Kurokawa, Tomoya; Nosu, Kiyoshi

This paper proposes an emotion estimation algorithm from e-Learning user's facial image. The algorithm characteristics are as follows: The criteria used to relate an e-Learning use's emotion to a representative emotion were obtained from the time sequential analysis of user's facial expressions. By examining the emotions of the e-Learning users and the positional change of the facial expressions from the experiment results, the following procedures are introduce to improve the estimation reliability; (1) some effective features points are chosen by the emotion estimation (2) dividing subjects into two groups by the change rates of the face feature points (3) selection of the eigenvector of the variance-co-variance matrices (cumulative contribution rate>=95%) (4) emotion calculation using Mahalanobis distance.

Distinct contributions of replication and transcription to mutation rate variation of human genomes.

PubMed

Cui, Peng; Ding, Feng; Lin, Qiang; Zhang, Lingfang; Li, Ang; Zhang, Zhang; Hu, Songnian; Yu, Jun

2012-02-01

Here, we evaluate the contribution of two major biological processes--DNA replication and transcription--to mutation rate variation in human genomes. Based on analysis of the public human tissue transcriptomics data, high-resolution replicating map of Hela cells and dbSNP data, we present significant correlations between expression breadth, replication time in local regions and SNP density. SNP density of tissue-specific (TS) genes is significantly higher than that of housekeeping (HK) genes. TS genes tend to locate in late-replicating genomic regions and genes in such regions have a higher SNP density compared to those in early-replication regions. In addition, SNP density is found to be positively correlated with expression level among HK genes. We conclude that the process of DNA replication generates stronger mutational pressure than transcription-associated biological processes do, resulting in an increase of mutation rate in TS genes while having weaker effects on HK genes. In contrast, transcription-associated processes are mainly responsible for the accumulation of mutations in highly-expressed HK genes. Copyright © 2012 Beijing Genomics Institute. Published by Elsevier Ltd. All rights reserved.

Roles of human papillomavirus infection and stathmin in the pathogenesis of sinonasal inverted papilloma.

PubMed

Lin, Hai; Lin, Dong; Xiong, Xi-Sheng

2016-02-01

The purpose of this study was to investigate roles of human papillomavirus (HPV) infection and stathmin in sinonasal inverted papilloma (SNIP). HPV DNA detection was performed by the fluorescence-based polymerase chain reaction (PCR) method. Stathmin protein expression was investigated by the immunohistochemistry method and mRNA expression of stathmin, Kif2a, and cyclin D1 were assessed by real-time PCR in SNIP and control subjects. The positive rate of HPV DNA detected in SNIP was about 53.6% (15 of 28). Recurrent cases showed a higher rate of HPV infection compared with initial cases and higher Krouse stage (T3 + T4) cases showed higher rate of HPV infection than lower Krouse stage (T1 + T2) cases. Stronger expression of stathmin, Kif2a, and cyclin D1 were observed in SNIP, especially HPV(+) SNIP. HPV infection was closely associated with recurrence and progression of SNIP. Stathmin is a valuable prognostic marker and could be considered as a therapeutic target in patients with SNIP. © 2015 Wiley Periodicals, Inc.

Risk of type 1 diabetes progression in islet autoantibody-positive children can be further stratified using expression patterns of multiple genes implicated in peripheral blood lymphocyte activation and function.

PubMed

Jin, Yulan; Sharma, Ashok; Bai, Shan; Davis, Colleen; Liu, Haitao; Hopkins, Diane; Barriga, Kathy; Rewers, Marian; She, Jin-Xiong

2014-07-01

There is tremendous scientific and clinical value to further improving the predictive power of autoantibodies because autoantibody-positive (AbP) children have heterogeneous rates of progression to clinical diabetes. This study explored the potential of gene expression profiles as biomarkers for risk stratification among 104 AbP subjects from the Diabetes Autoimmunity Study in the Young (DAISY) using a discovery data set based on microarray and a validation data set based on real-time RT-PCR. The microarray data identified 454 candidate genes with expression levels associated with various type 1 diabetes (T1D) progression rates. RT-PCR analyses of the top-27 candidate genes confirmed 5 genes (BACH2, IGLL3, EIF3A, CDC20, and TXNDC5) associated with differential progression and implicated in lymphocyte activation and function. Multivariate analyses of these five genes in the discovery and validation data sets identified and confirmed four multigene models (BI, ICE, BICE, and BITE, with each letter representing a gene) that consistently stratify high- and low-risk subsets of AbP subjects with hazard ratios >6 (P < 0.01). The results suggest that these genes may be involved in T1D pathogenesis and potentially serve as excellent gene expression biomarkers to predict the risk of progression to clinical diabetes for AbP subjects. © 2014 by the American Diabetes Association.

The clinicopathological parameters and prognostic significance of HER2 expression in gastric cancer patients: a meta-analysis of literature.

PubMed

Lei, Yu-Ying; Huang, Jin-Yu; Zhao, Qiong-Rui; Jiang, Nan; Xu, Hui-Mian; Wang, Zhen-Ning; Li, Hai-Qing; Zhang, Shi-Bo; Sun, Zhe

2017-03-21

Human epidermal growth factor receptor-2 (HER2) is regarded as an important and promising target in the treatment of HER2-positive breast cancers. However, the correlation of clinicopathological characteristics and prognostic significance of HER2 overexpression in gastric cancer patients remains unclear. Our aim was to clarify this issue. Embase, PubMed, and the Cochrane Library were searched for relevant articles published up to May 2016. Outcomes of interest contained sex, age, tumor size, tumor site, tumor node metastasis (TNM) stage, distant metastasis, lymph node metastasis, Lauren's classification, differentiation grade, lymphovascular invasion, neural invasion, and multivariate analysis data for overall survival. A total of 41 studies of 17,494 gastric cancer patients were identified with HER2 test. HER2 positive rate was 19.07% (95% CI = 9.16, 28.98). There existed statistical significance between HER2 overexpression and patients' prognosis (RR = 1.47, 95% CI = 1.09, 1.98). Male patients (OR = 1.48, 95% CI = 1.34, 1.65), proximal tumors (OR = 1.25, 95% CI = 1.07, 1.47), intestinal-type tumors (OR = 3.37, 95% CI = 2.54, 4.47), advanced stage cancers (OR = 1.35, 95% CI = 1.10, 1.66), lymph node metastasis (OR = 1.26, 95% CI = 1.14, 1.41), well-differentiated cancers (OR = 1.79, 95% CI = 1.15, 2.76), and distant metastasis (OR = 1.91, 95% CI = 1.08, 3.38) were correlated with higher HER2 expression rates. However, no statistical differences existed in age, tumor size, lymphovascular invasion, or neural invasion. Subgroup analysis revealed that HER2 expression rates reported in articles from Asian (19.52%) countries were quantitatively higher than those from European (16.91%) areas. Results were consistent with those reports that define HER2 status according to trastuzumab for gastric cancer (ToGA) criteria. This study showed that HER2 overexpression was associated with poor prognosis in gastric cancer patients. HER2 positive rates may be associated with sex, tumor site, TNM staging system, distant metastasis, lymph node metastasis, Lauren's classification, and differentiation grade in gastric cancer patients. The HER2 expression rate in Asians may be higher than that in Europeans. This study offers a convenient way for doctors to select patients for relevant HER2 detection and following treatment.

Expression of Bmi-1, P16, and CD44v6 in Uterine Cervical Carcinoma and Its Clinical Significance.

PubMed

Weng, Mei-Ying; Li, Lin; Feng, Shu-Ying; Hong, Shun-Jia

2012-03-01

Bmi-1, a putative proto-oncogene, is a core member of the polycomb gene family, which is expressed in many human tumors. The p16 protein negatively regulated cell proliferation, whereas CD44v6 is associated with proliferation as an important protein. Additionally, CD44v6 is an important nuclear antigen closely correlated to tumor metastasis. The present study aims to investigate the expression and significance of Bmi-1, p16, and CD44v6 in uterine cervical carcinoma (UCC). A total of 62 UCC, 30 cervical neoplasic, and 20 normal cervical mucosal tissues were used in the current study. The expression of Bmi-1, p16, and CD44v6 in these tissues was determined using immunohistochemical assay. The relationships among the expression of these indices, the clinicopathologic features of UCC, and the survival rate of UCC patients were also discussed. The correlation between Bmi-1 protein expression and p16 or CD44v6 protein in UCC was analyzed. The expression of Bmi-1, p16, and CD44v6 was significantly high in cervical carcinoma compared with that in the cervical neoplasia and normal colorectal mucosa (P<0.05). The over-expression of Bmi-1 protein in UCC was apparently related to the distant metastasis (P<0.01) and the tumor, nodes and metastasis-classification, i.e. the TNM staging, World Health Organization (P<0.05). Nevertheless, the positive expression of p16 protein in UCC was not significantly associated with the clinicopathologic features (P>0.05). The Kaplan-Meier survival analysis showed that the over-expression of Bmi-1 significantly decreased the survival rate of UCC patients (P<0.05). A strong correlation indicated that there was statistical significance between the expression of Bmi-1 and CD44V6 proteins in UCC (r=0.419, P=0.001). The over-expression of Bmi-1 and CD44v6 protein closely correlate to the tumorigenesis, metastasis, and prognosis of UCC. Bmi-1 and CD44v6 may be used to predict the prognosis of cervical carcinoma. Bmi-1 may indirectly regulate the expression of CD44v6 in UCC patients. The positive expression of p16 protein is possibly associated with the tumorigenesis, but not with the metastasis or prognosis of UCC.

A pilot study of durvalumab and tremelimumab and immunogenomic dynamics in metastatic breast cancer

PubMed Central

Santa-Maria, Cesar August; Kato, Taigo; Park, Jae-Hyun; Kiyotani, Kazuma; Rademaker, Alfred; Shah, Ami N.; Gross, Leeaht; Blanco, Luis Z.; Jain, Sarika; Flaum, Lisa; Tellez, Claudia; Stein, Regina; Uthe, Regina; Gradishar, William J.; Cristofanilli, Massimo; Nakamura, Yusuke; Giles, Francis J.

2018-01-01

Immune checkpoint inhibitors produce modest responses in metastatic breast cancer, however, combination approaches may improve responses. A single arm pilot study was designed to determine the overall response rate (ORR) of durvalumab and tremelimumab, and evaluate immunogenomic dynamics in metastatic endocrine receptor (ER) positive or triple negative breast cancer (TNBC). Simon two-stage design indicated at least four responses from the first 18 patients were needed to proceed with the second stage. T-cell receptor (TCR) sequencing and immune-gene expression profiling were conducted at baseline and two months, whole exome sequencing was conducted at baseline. Eighteen evaluable patients were accrued (11 ER-positive; seven TNBC). Only three patients had a response (ORR = 17%), thus the study did not proceed to the second stage. Responses were only observed in patients with TNBC (ORR = 43%). Responders versus non-responders had upregulation of CD8, granzyme A, and perforin 1 gene expression, and higher mutational and neoantigen burden. Patients with TNBC had an oligoclonal shift of the most abundant TCR-beta clonotypes compared to those with ER-positive disease, p = 0.004. We conclude responses are low in unselected metastatic breast cancer, however, higher rates of clinical benefit were observed in TNBC. Immunogenomic dynamics may help identify phenotypes most likely to respond to immunotherapy. PMID:29721177

Diffusion in shear flow

NASA Astrophysics Data System (ADS)

Dufty, J. W.

1984-09-01

Diffusion of a tagged particle in a fluid with uniform shear flow is described. The continuity equation for the probability density describing the position of the tagged particle is considered. The diffusion tensor is identified by expanding the irreversible part of the probability current to first order in the gradient of the probability density, but with no restriction on the shear rate. The tensor is expressed as the time integral of a nonequilibrium autocorrelation function for the velocity of the tagged particle in its local fluid rest frame, generalizing the Green-Kubo expression to the nonequilibrium state. The tensor is evaluated from results obtained previously for the velocity autocorrelation function that are exact for Maxwell molecules in the Boltzmann limit. The effects of viscous heating are included and the dependence on frequency and shear rate is displayed explicitly. The mode-coupling contributions to the frequency and shear-rate dependent diffusion tensor are calculated.

Comparison of small biopsy specimens and surgical specimens for the detection of EGFR mutations and EML4-ALK in non-small-cell lung cancer

PubMed Central

Xiao, DeSheng; Lu, Can; Zhu, Wei; He, QiuYan; Li, Yong; Fu, ChunYan; Zhou, JianHua; Liu, Shuang; Tao, YongGuang

2016-01-01

Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) fusion genes represent novel oncogenes that are associated with non–small-cell lung cancers (NSCLC). The feasibility of detecting EGFR mutations and ALK fusion genes in small biopsy specimens or surgical specimens was determined. Of the 721 NSCLC patients, a total of 305 cases were positive for EGFR mutations (42.3%). The rate of EGFR mutations in women was significantly higher than that in men. Histologically, the EGFR mutation rate in adenocarcinomas was significantly higher than that in squamous cell carcinomas. No difference in the EGFR mutation rate was observed between surgical specimens (42.1%) and small biopsy specimens (42.4%), which indicated that the EGFR mutation ratios in surgical specimens and small biopsy specimens were not different. In 385 NSCLC patients, 26 cases were positive for EML4-ALK (6.8%). However, 11.7% of the surgical specimens were EML4-ALK-positive, whereas the positive proportion in the small biopsy specimens was only 4.7%, which indicated that EML4-ALK-positive rate in the surgical specimens was significantly higher than that in the small biopsy specimens. Detection of EGFR gene mutations was feasible in small biopsy specimens, and screening for EML4-ALK expression in small biopsy specimens can be used to guide clinical treatments. PMID:27322143

Comparison of small biopsy specimens and surgical specimens for the detection of EGFR mutations and EML4-ALK in non-small-cell lung cancer.

PubMed

Xiao, DeSheng; Lu, Can; Zhu, Wei; He, QiuYan; Li, Yong; Fu, ChunYan; Zhou, JianHua; Liu, Shuang; Tao, YongGuang

2016-09-13

Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) fusion genes represent novel oncogenes that are associated with non-small-cell lung cancers (NSCLC). The feasibility of detecting EGFR mutations and ALK fusion genes in small biopsy specimens or surgical specimens was determined. Of the 721 NSCLC patients, a total of 305 cases were positive for EGFR mutations (42.3%). The rate of EGFR mutations in women was significantly higher than that in men. Histologically, the EGFR mutation rate in adenocarcinomas was significantly higher than that in squamous cell carcinomas. No difference in the EGFR mutation rate was observed between surgical specimens (42.1%) and small biopsy specimens (42.4%), which indicated that the EGFR mutation ratios in surgical specimens and small biopsy specimens were not different. In 385 NSCLC patients, 26 cases were positive for EML4-ALK (6.8%). However, 11.7% of the surgical specimens were EML4-ALK-positive, whereas the positive proportion in the small biopsy specimens was only 4.7%, which indicated that EML4-ALK-positive rate in the surgical specimens was significantly higher than that in the small biopsy specimens. Detection of EGFR gene mutations was feasible in small biopsy specimens, and screening for EML4-ALK expression in small biopsy specimens can be used to guide clinical treatments.

High expression of SDF-1 and VEGF is associated with poor prognosis in patients with synovial sarcomas.

PubMed

Feng, Qi; Guo, Peng; Wang, Jin; Zhang, Xiaoyu; Yang, Hui-Chai; Feng, Jian-Gang

2018-03-01

Stromal cell-derived factor-1 (SDF-1) predicts poor clinical outcomes of certain types of cancer. Furthermore, vascular endothelial growth factor (VEGF) promotes the growth and metastasis of solid tumors. The aim of the present study was to examine the expression of SDF-1 and VEGF in patients with synovial sarcoma and to determine their expression is correlated with unfavorable outcomes. Levels of SDF-1 and VEGF proteins were evaluated in 54 patients with synovial sarcoma using immunohistochemical and immunofluorescence staining. Potential associations between the expression of SDF-1 and VEGF and various clinical parameters were analyzed using Pearson's χ 2 test and the Spearman-rho test. Additionally, univariate and multivariate Cox regression analyses were used to identify potential prognostic factors, and the Kaplan-Meier method was used to analyze the overall survival rates of patients. Low SDF-1 and VEGF expression was detected in 20.4% (11/54) and 22.2% (12/54) of patients with synovial sarcoma; moderate expression was detected in 35.2% (19/54) and 37.0% (20/54) of patients and high expression was detected in 44.4% (24 of 54) and 40.7% (22 of 54) of patients, respectively. Levels of SDF-1 and VEGF proteins were significantly associated with histological grade (P<0.05), metastasis (P<0.05) and American Joint Committee on Cancer staging (P<0.05). In addition, levels of SDF-1 and VEGF expression were positively correlated with each other (P<0.001). Univariate analysis also indicated that VEGF expression was associated with shorter overall survival rates in (P<0.05), whereas multivariate analysis demonstrated that SDF-1 expression was associated with shorter patient survival rates (P<0.05). Finally, both SDF-1 and VEGF expression were associated with various characteristics of synovial sarcoma. Therefore, SDF-1 expression may be a potential independent prognostic indicator in patients with synovial sarcomas.

Differences in expression of the cancer stem cell marker aldehyde dehydrogenase 1 among estrogen receptor-positive/human epidermal growth factor receptor type 2-negative breast cancer cases with early, late, and no recurrence.

PubMed

Miyoshi, Yuichiro; Shien, Tadahiko; Ogiya, Akiko; Ishida, Naoko; Yamazaki, Kieko; Horii, Rie; Horimoto, Yoshiya; Masuda, Norikazu; Yasojima, Hiroyuki; Inao, Touko; Osako, Tomofumi; Takahashi, Masato; Tomioka, Nobumoto; Endo, Yumi; Hosoda, Mitsuchika; Doihara, Hiroyoshi; Miyoshi, Shinichiro; Yamashita, Hiroko

2016-07-02

The significance of the expression of aldehyde dehydrogenase 1 (ALDH1), a cancer stem cell marker, for predicting the recurrence of estrogen receptor (ER)-positive/human epidermal growth factor receptor type 2 (HER2)-negative breast cancer is still poorly understood. The value of ALDH1 in predicting the time of recurrence remains unknown. In total, 184 patients with early distant recurrence, 134 patients with late distant recurrence, and 321 control patients without recurrence for more than 10 years after starting initial treatment for ER-positive/HER2-negative breast cancer, registered in 9 institutions, were analyzed. We assessed relationships between ALDH1 and other clinicopathological features, and ALDH1 expression was compared among the three groups. The relationship between ALDH1 expression and overall survival after recurrence was also evaluated in each group. The rates of ALDH1 expression positivity (more than 1 %) in the early, late, and no recurrence groups were 18.4 %, 13.4 %, and 8.4 %, respectively. ALDH1 expression correlated significantly with lymph node metastases (p = 0.048) and the Ki-67 labeling index (p < 0.001) in the early recurrence group. Multivariate analysis revealed ALDH1 expression to be significantly higher in the early recurrence group than in the no recurrence group (adjusted OR 2.140, 95 % CI 1.144-4.003, p = 0.016). Moreover, there was a significant difference in ALDH1 expression between the early and no recurrence groups receiving adjuvant endocrine therapy and chemotherapy (adjusted OR 4.625, 95 % CI 1.881-12.474, p < 0.001). However, there was no difference in ALDH1 expression between the late and no recurrence groups in univariate analysis (OR 1.507, 95 % CI 0.738-2.998, p = 0.253). In multivariate analysis, ALDH1 was not a factor independently predicting overall survival after the detection of recurrence (adjusted OR 1.451, 95 % CI 0.985-2.085, p = 0.059). Among patients with ER-positive/HER2-negative breast cancer, ALDH1 expression was more common in those with early recurrence, and this expression was found to be associated with a more aggressive breast cancer phenotype than that in the patients without recurrence. Further study is needed to clarify the prognostic significance of the heterogeneity of cancer stem cells and to confirm their role in resistance to chemotherapy.

Distinguishing the rates of gene activation from phenotypic variations.

PubMed

Chen, Ye; Lv, Cheng; Li, Fangting; Li, Tiejun

2015-06-18

Stochastic genetic switching driven by intrinsic noise is an important process in gene expression. When the rates of gene activation/inactivation are relatively slow, fast, or medium compared with the synthesis/degradation rates of mRNAs and proteins, the variability of protein and mRNA levels may exhibit very different dynamical patterns. It is desirable to provide a systematic approach to identify their key dynamical features in different regimes, aiming at distinguishing which regime a considered gene regulatory network is in from their phenotypic variations. We studied a gene expression model with positive feedbacks when genetic switching rates vary over a wide range. With the goal of providing a method to distinguish the regime of the switching rates, we first focus on understanding the essential dynamics of gene expression system in different cases. In the regime of slow switching rates, we found that the effective dynamics can be reduced to independent evolutions on two separate layers corresponding to gene activation and inactivation states, and the transitions between two layers are rare events, after which the system goes mainly along deterministic ODE trajectories on a particular layer to reach new steady states. The energy landscape in this regime can be well approximated by using Gaussian mixture model. In the regime of intermediate switching rates, we analyzed the mean switching time to investigate the stability of the system in different parameter ranges. We also discussed the case of fast switching rates from the viewpoint of transition state theory. Based on the obtained results, we made a proposal to distinguish these three regimes in a simulation experiment. We identified the intermediate regime from the fact that the strength of cellular memory is lower than the other two cases, and the fast and slow regimes can be distinguished by their different perturbation-response behavior with respect to the switching rates perturbations. We proposed a simulation experiment to distinguish the slow, intermediate and fast regimes, which is the main point of our paper. In order to achieve this goal, we systematically studied the essential dynamics of gene expression system when the switching rates are in different regimes. Our theoretical understanding provides new insights on the gene expression experiments.

[Knockdown of NEDD9 inhibits the proliferation, invasion and migration of esophageal carcinoma EC109 cells].

PubMed

Zhang, Wen; Li, Shaojun; Zhao, Yunlong; Guo, Nannan; Li, Yingjie

2016-12-01

Objective To observe the expression of the neural precursor cell expressed, developmentally down-regulated 9 (NEDD9) in esophageal cancer, to investigate the impact of decreased expression of NEDD9 on invasion and migration, and to explicit the function of NEDD9 in EC109 human esophageal cancer cell line. Methods Immunohistochemical staining was used to detect the expression of NEDD9 in human esophageal cancer tissues and paracancerous normal tissues. RNA interfering (RNAi) was used to knockdown NEDD9 in EC109 cells. The interference efficiency was detected by reverse transcription PCR (RT-PCR) and Western blot analysis. Cell proliferation was determined by MTT assay and the invasion and migration abilities of EC109 cells were monitored by Transwell TM assay. The protein levels of proliferating cell nuclear antigen (PCNA), Bax and Bcl-2 were tested by Western blotting. Results The positive expression rate of NEDD9 in esophageal carcinoma tissues was significantly higher compared with that in the paracancerous tissues. After NEDD9 expression was successfully downregulated in EC109 cells by siRNA, the proliferation, invasion and migration rates in transfection group were significantly lower than those in control group; meanwhile, the expression of Bcl-2 was reduced and Bax expression was enhanced. Conclusion The protein expression level of NEDD9 is higher in esophageal carcinoma tissues than that in adjacent normal tissues. Knockdown of NEDD9 expression can restrain the proliferation, invasion and migration of EC109 cells.

Behavioral and Physiological Correlates of Children's Reactions to Others in Distress.

ERIC Educational Resources Information Center

Fabes, Richard A.; And Others

1993-01-01

Measured the facial expressions, heart rate variability (HRV), and skin conductance of 37 third graders and 29 sixth graders while they viewed a film about a distressed child. Found that high HRV was predictive of children's sympathetic rather than distressed reactions and that, for boys, sympathetic responsiveness positively predicted a…

The Role of Hox Genes in Female Reproductive Tract Development, Adult Function, and Fertility.

PubMed

Du, Hongling; Taylor, Hugh S

2015-11-09

HOX genes convey positional identity that leads to the proper partitioning and adult identity of the female reproductive track. Abnormalities in reproductive tract development can be caused by HOX gene mutations or altered HOX gene expression. Diethylstilbestrol (DES) and other endocrine disruptors cause Müllerian defects by changing HOX gene expression. HOX genes are also essential regulators of adult endometrial development. Regulated HOXA10 and HOXA11 expression is necessary for endometrial receptivity; decreased HOXA10 or HOXA11 expression leads to decreased implantation rates. Alternation of HOXA10 and HOXA11 expression has been identified as a mechanism of the decreased implantation associated with endometriosis, polycystic ovarian syndrome, leiomyoma, polyps, adenomyosis, and hydrosalpinx. Alteration of HOX gene expression causes both uterine developmental abnormalities and impaired adult endometrial development that prevent implantation and lead to female infertility. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

Body mass index and risk of colorectal cancer according to fatty acid synthase expression in the nurses' health study.

PubMed

Kuchiba, Aya; Morikawa, Teppei; Yamauchi, Mai; Imamura, Yu; Liao, Xiaoyun; Chan, Andrew T; Meyerhardt, Jeffrey A; Giovannucci, Edward; Fuchs, Charles S; Ogino, Shuji

2012-03-07

Fatty acid synthase (FASN) plays an important role in energy metabolism of fatty acids and is overexpressed in some colon cancers. We investigated whether associations between body mass index (BMI) and risk of colorectal cancer varied according to FASN expression. During follow-up of 109,051 women in the ongoing prospective Nurses' Health Study, a total of 1351 incident colon and rectal cancers were diagnosed between 1986 and 2004. We constructed tissue microarrays of the available resected tumor samples (n = 536), and FASN expression was analyzed by immunohistochemistry. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. All statistical tests were two-sided. High BMI was associated with an increased risk of FASN-negative (no or weak expression) colorectal cancer compared with normal BMI (high BMI [≥ 30 kg/m(2)], ie, obese vs normal BMI [18.5-22.9 kg/m(2)], HR = 2.25, 95% CI = 1.49 to 3.40, P(trend) < .001) but not with FASN-positive (moderate to strong expression) colorectal cancer. A statistically significant heterogeneity in colorectal cancer risks was observed between FASN-negative and FASN-positive tumors (P(heterogeneity) = .033). The age-adjusted incidence rates for FASN-positive and FASN-negative colorectal cancers were 10.9 and 7.1, respectively, per 100,000 person-years. This molecular pathological epidemiology study supports a role of energy metabolism in colorectal cancer pathogenesis.

Younger and older adults' beliefs about the experience and expression of emotions across the life span.

PubMed

Montepare, Joann M; Dobish, Heidi

2014-11-01

Although theorists acknowledge that beliefs about emotions may play a role in age-related emotion behavior, no research has explored these beliefs. This research examined beliefs about the experience and expression of emotions across the life span, especially across the adult years. Younger and older adults rated the extent to which infants, children, adolescents, young adults, middle-aged adults, and older adults were likely to experience and express a range of emotions. Younger and older adults held similar beliefs about the course of emotions across the life span. Moreover, these beliefs differed across emotion categories. In particular, although older adults were believed to experience and express fewer highly charged, negative emotions, they were expected to be more likely to experience and express positive, low arousal emotions, as well as negative, low arousal emotions. The experience and expression of positive, high arousal emotions were seen as more characteristic of very young age groups as opposed to older age groups. These findings beg questions about if and how beliefs about emotion may affect age-related emotion regulation strategies and other everyday emotion-focused behaviors, as well as social reactions to older adults observed experiencing and expressing particular types of emotions. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Regulatory elements involved in constitutive and phorbol ester-inducible expression of the plasminogen activator inhibitor type 2 gene promoter.

PubMed Central

Cousin, E; Medcalf, R L; Bergonzelli, G E; Kruithof, E K

1991-01-01

Gene transcription rates and mRNA levels of plasminogen activator inhibitor type 2 (PAI-2) are markedly induced by the tumor promoting agent phorbol 12-myristate 13-acetate (PMA) in human HT1080 fibrosarcoma cells. To identify promoter elements required for basal-, and phorbol ester-inducible expression, deletion mutants of the PAI-1 promoter fused to the chloramphenicol acetyl transferase (CAT) reporter gene, were transiently expressed in HT1080 cells. Constitutive CAT activity was expressed from constructs containing more than 215 bp of promoter sequence, whereas deletion to position -91 bp abolished CAT gene expression. Treatment of transfected cells with PMA resulted in a three- to ten-fold increase in CAT expression from all constructs except from the construct shortened to position -91. DNAse1 protection analysis of the promoter region between -215 and the transcription initiation site revealed numerous protected regions, including two AP1-like binding sites (AP1a and AP1b) and one CRE-like element. Site-directed mutagenesis of the AP1a site or of the CRE-like site resulted in the loss of basal CAT activity and abolished the PMA effect, whereas mutagenesis of AP1b only partially inhibited basal and PMA-mediated expression. Our results suggest that the PAI-2 promoter contains at least two elements required for basal gene transcription and PMA-mediated induction. Images PMID:1650454

Isolation and characterization of novel RECK tumor suppressor gene splice variants

PubMed Central

Trombetta-Lima, Marina; Winnischofer, Sheila Maria Brochado; Demasi, Marcos Angelo Almeida; Filho, Renato Astorino; Carreira, Ana Claudia Oliveira; Wei, Beiyang; de Assis Ribas, Thais; Konig, Michelle Silberspitz; Bowman-Colin, Christian; Oba-Shinjo, Sueli Mieko; Marie, Suely Kazue Nagahashi; Stetler-Stevenson, William; Sogayar, Mari Cleide

2015-01-01

Glioblastoma multiforme is the most common and lethal of the central nervous system glial-derived tumors. RECK suppresses tumor invasion by negatively regulating at least three members of the matrix metalloproteinase family: MMP-9, MMP-2, and MT1-MMP. A positive correlation has been observed between the abundance of RECK expression in tumor samples and a more favorable prognosis for patients with several types of tumors. In the present study, novel alternatively spliced variants of the RECK gene: RECK-B and RECK-I were isolated by RT-PCR and sequenced. The expression levels and profiles of these alternative RECK transcripts, as well as canonical RECK were determined in tissue samples of malignant astrocytomas of different grades and in a normal tissue RNA panel by qRT-PCR. Our results show that higher canonical RECK expression, accompanied by a higher canonical to alternative transcript expression ratio, positively correlates with higher overall survival rate after chemotherapeutic treatment of GBM patients. U87MG and T98G cells over-expressing the RECK-B alternative variant display higher anchorage-independent clonal growth and do not display modulation of, respectively, MMP-2 and MMP-9 expression. Our findings suggest that RECK transcript variants might have opposite roles in GBM biology and the ratio of their expression levels may be informative for the prognostic outcome of GBM patients. PMID:26431549

Amplification of ABA biosynthesis and signaling through a positive feedback mechanism in seeds.

PubMed

Nonogaki, Mariko; Sall, Khadidiatou; Nambara, Eiji; Nonogaki, Hiroyuki

2014-05-01

Abscisic acid is an essential hormone for seed dormancy. Our previous study using the plant gene switch system, a chemically induced gene expression system, demonstrated that induction of 9-cis-epoxycarotenoid dioxygenase (NCED), a rate-limiting ABA biosynthesis gene, was sufficient to suppress germination in imbibed Arabidopsis seeds. Here, we report development of an efficient experimental system that causes amplification of NCED expression during seed maturation. The system was created with a Triticum aestivum promoter containing ABA responsive elements (ABREs) and a Sorghum bicolor NCED to cause ABA-stimulated ABA biosynthesis and signaling, through a positive feedback mechanism. The chimeric gene pABRE:NCED enhanced NCED and ABF (ABRE-binding factor) expression in Arabidopsis Columbia-0 seeds, which caused 9- to 73-fold increases in ABA levels. The pABRE:NCED seeds exhibited unusually deep dormancy which lasted for more than 3 months. Interestingly, the amplified ABA pathways also caused enhanced expression of Arabidopsis NCED5, revealing the presence of positive feedback in the native system. These results demonstrated the robustness of positive feedback mechanisms and the significance of NCED expression, or single metabolic change, during seed maturation. The pABRE:NCED system provides an excellent experimental system producing dormant and non-dormant seeds of the same maternal origin, which differ only in zygotic ABA. The pABRE:NCED seeds contain a GFP marker which enables seed sorting between transgenic and null segregants and are ideal for comparative analysis. In addition to its utility in basic research, the system can also be applied to prevention of pre-harvest sprouting during crop production, and therefore contributes to translational biology. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

Overexpression of centrosomal protein Nlp confers breast carcinoma resistance to paclitaxel.

PubMed

Zhao, Weihong; Song, Yongmei; Xu, Binghe; Zhan, Qimin

2012-02-01

Nlp (ninein-like protein), an important molecule involved in centrosome maturation and spindle formation, plays an important role in tumorigenesis and its abnormal expression was recently observed in human breast and lung cancers. In this study, the correlation between overexpression of Nlp and paclitaxel chemosensitivity was investigated to explore the mechanisms of resistance to paclitaxel and to understand the effect of Nlp upon apoptosis induced by chemotherapeutic agents. Nlp expression vector was stably transfected into breast cancer MCF-7 cells. With Nlp overexpression, the survival rates, cell cycle distributions and apoptosis were analyzed in transfected MCF-7 cells by MTT test and FCM approach. The immunofluorescent assay was employed to detect the changes of microtubule after paclitaxel treatment. Immunoblotting analysis was used to examine expression of centrosomal proteins and apoptosis associated proteins. Subsequently, Nlp expression was retrospectively examined with 55 breast cancer samples derived from paclitaxel treated patients. Interestingly, the survival rates of MCF-7 cells with Nlp overexpressing were higher than that of control after paclitaxel treatment. Nlp overexpression promoted G2-M arrest and attenuated apoptosis induced by paclitaxel, which was coupled with elevated Bcl-2 protein. Nlp expression significantly lessened the microtubule polymerization and bundling elicited by paclitaxel attributing to alteration on the structure or dynamics of β-tubulin but not on its expression. The breast cancer patients with high expression of Nlp were likely resistant to the treatment of paclitaxel, as the response rate in Nlp negative patients was 62.5%, whereas was 58.3 and 15.8% in Nlp (+) and Nlp (++) patients respectively (p = 0.015). Nlp expression was positive correlated with those of Plk1 and PCNA. These findings provide insights into more rational chemotherapeutic regimens in clinical practice, and more effective approaches might be developed through targeting Nlp to increase chemotherapeutic sensitivity.

University Sports Rivalries Provide Insights on Coalitional Psychology : Territorial Context Influences Reactions to Vocal Signals of Allegiance.

PubMed

Kruger, Daniel J; Falbo, Michael; Blanchard, Sophie; Cole, Ethan; Gazoul, Camille; Nader, Noreen; Murphy, Shannon

2018-05-11

Sports are an excellent venue for demonstrating evolutionary principles to audiences not familiar with academic research. Team sports and sports fandom feature dynamics of in-group loyalty and intergroup competition, influenced by our evolved coalitional psychology. We predicted that reactions to expressions signaling mutual team/group allegiance would vary as a function of the territorial context. Reactions should become more prevalent, positive, and enthusiastic as one moves from the home territory to a contested area, and from a contested area to a rival's territory during active rival engagement. We also predicted that men would be more responsive than women based on sex differences in evolved coalitional psychology. The research team visited public places immediately prior to 2016-2017 collegiate football and basketball games. A male research confederate wore a sweatshirt displaying the logo of one of the competing university teams and vocalized the team's most popular slogan when he saw a fan displaying similar logos. Observers followed 5 m behind, recording reactions (N = 597) and response positivity/enthusiasm. Reaction tone was most positive in the rival territory, least positive in the home territory, and intermediate in the periphery and contested territory. Rates of "no reaction" were lowest in the rival territory but were highest in the periphery. Men had higher reaction rates and more positive and enthusiastic reaction tones than women. Reactions generally followed predictions based on expected signal value. This project provides evidence that coalitional psychology influences dynamics related to university sports team rivalries and that context matters for expressions of alliance.

A Stromal Immune Module Correlated with the Response to Neoadjuvant Chemotherapy, Prognosis and Lymphocyte Infiltration in HER2-Positive Breast Carcinoma Is Inversely Correlated with Hormonal Pathways

PubMed Central

Lae, Marick; Moarii, Matahi; Sadacca, Benjamin; Pinheiro, Alice; Galliot, Marion; Abecassis, Judith; Laurent, Cecile; Reyal, Fabien

2016-01-01

Introduction HER2-positive breast cancer (BC) is a heterogeneous group of aggressive breast cancers, the prognosis of which has greatly improved since the introduction of treatments targeting HER2. However, these tumors may display intrinsic or acquired resistance to treatment, and classifiers of HER2-positive tumors are required to improve the prediction of prognosis and to develop novel therapeutic interventions. Methods We analyzed 2893 primary human breast cancer samples from 21 publicly available datasets and developed a six-metagene signature on a training set of 448 HER2-positive BC. We then used external public datasets to assess the ability of these metagenes to predict the response to chemotherapy (Ignatiadis dataset), and prognosis (METABRIC dataset). Results We identified a six-metagene signature (138 genes) containing metagenes enriched in different gene ontologies. The gene clusters were named as follows: Immunity, Tumor suppressors/proliferation, Interferon, Signal transduction, Hormone/survival and Matrix clusters. In all datasets, the Immunity metagene was less strongly expressed in ER-positive than in ER-negative tumors, and was inversely correlated with the Hormonal/survival metagene. Within the signature, multivariate analyses showed that strong expression of the “Immunity” metagene was associated with higher pCR rates after NAC (OR = 3.71[1.28–11.91], p = 0.019) than weak expression, and with a better prognosis in HER2-positive/ER-negative breast cancers (HR = 0.58 [0.36–0.94], p = 0.026). Immunity metagene expression was associated with the presence of tumor-infiltrating lymphocytes (TILs). Conclusion The identification of a predictive and prognostic immune module in HER2-positive BC confirms the need for clinical testing for immune checkpoint modulators and vaccines for this specific subtype. The inverse correlation between Immunity and hormone pathways opens research perspectives and deserves further investigation. PMID:28005906

RNA-Seq Mouse Brain Regions Expression Data Analysis: Focus on ApoE Functional Network

PubMed

Babenko, Vladimir N; Smagin, Dmitry A; Kudryavtseva, Natalia N

2017-09-13

ApoE expression status was proved to be a highly specific marker of energy metabolism rate in the brain. Along with its neighbor, Translocase of Outer Mitochondrial Membrane 40 kDa (TOMM40) which is involved in mitochondrial metabolism, the corresponding genomic region constitutes the neuroenergetic hotspot. Using RNA-Seq data from a murine model of chronic stress a significant positive expression coordination of seven neighboring genes in ApoE locus in five brain regions was observed. ApoE maintains one of the highest absolute expression values genome-wide, implying that ApoE can be the driver of the neighboring gene expression alteration observed under stressful loads. Notably, we revealed the highly statistically significant increase of ApoE expression in the hypothalamus of chronically aggressive (FDR < 0.007) and defeated (FDR < 0.001) mice compared to the control. Correlation analysis revealed a close association of ApoE and proopiomelanocortin (Pomc) gene expression profiles implying the putative neuroendocrine stress response background of ApoE expression elevation therein.

Identification of Genes Whose Expression Profile Is Associated with Non-Progression towards AIDS Using eQTLs

PubMed Central

Le Clerc, Sigrid; van Manen, Daniëlle; Coulonges, Cédric; Ulveling, Damien; Laville, Vincent; Labib, Taoufik; Taing, Lieng; Delaneau, Olivier; Montes, Matthieu; Schuitemaker, Hanneke; Zagury, Jean-François

2015-01-01

Background Many genome-wide association studies have been performed on progression towards the acquired immune deficiency syndrome (AIDS) and they mainly identified associations within the HLA loci. In this study, we demonstrate that the integration of biological information, namely gene expression data, can enhance the sensitivity of genetic studies to unravel new genetic associations relevant to AIDS. Methods We collated the biological information compiled from three databases of expression quantitative trait loci (eQTLs) involved in cells of the immune system. We derived a list of single nucleotide polymorphisms (SNPs) that are functional in that they correlate with differential expression of genes in at least two of the databases. We tested the association of those SNPs with AIDS progression in two cohorts, GRIV and ACS. Tests on permuted phenotypes of the GRIV and ACS cohorts or on randomised sets of equivalent SNPs allowed us to assess the statistical robustness of this method and to estimate the true positive rate. Results Eight genes were identified with high confidence (p = 0.001, rate of true positives 75%). Some of those genes had previously been linked with HIV infection. Notably, ENTPD4 belongs to the same family as CD39, whose expression has already been associated with AIDS progression; while DNAJB12 is part of the HSP90 pathway, which is involved in the control of HIV latency. Our study also drew our attention to lesser-known functions such as mitochondrial ribosomal proteins and a zinc finger protein, ZFP57, which could be central to the effectiveness of HIV infection. Interestingly, for six out of those eight genes, down-regulation is associated with non-progression, which makes them appealing targets to develop drugs against HIV. PMID:26367535

Does endometrial integrin expression in endometriosis patients predict enhanced in vitro fertilization cycle outcomes after prolonged GnRH agonist therapy?

PubMed

Surrey, Eric S; Lietz, Annette K; Gustofson, Robert L; Minjarez, Debra A; Schoolcraft, William B

2010-02-01

To determine whether endometrial expression of the integrin alpha(v)beta(3) vitronectin can predict which endometriosis patient subgroup will benefit from pre-IVF cycle prolonged GnRH agonist (GnRHa) therapy. Prospective randomized institutional review board approved pilot trial. Private assisted reproductive technology program. IVF candidates with regular menses, surgically confirmed endometriosis, and normal ovarian reserve. All patients underwent endometrial biopsy 9 to 11 days post-LH surge to evaluate alpha(v)beta(3) integrin expression. Patients were randomized either to receive depot leuprolide acetate 3.75 mg every 28 days for three doses before controlled ovarian hyperstimulation (COH) or to proceed directly to COH and IVF. Group 1: integrin-positive controls (N = 12); group 2: integrin-positive administered prolonged GnRHa (N = 8). Group A: integrin-negative controls (N = 7); group B: integrin-negative administered prolonged GnRHa (N = 9). COH responses, ongoing pregnancy and implantation rates. There were no significant effects of GnRH agonist treatment in either of the integrin expression strata regarding ongoing pregnancy or implantation rates, although these outcomes were more frequent in group 2 vs. 1 (62.5% vs. 41.6% and 35% vs. 20.6%, respectively). This effect may have because of limited sample size. The value of a negative integrin biopsy in predicting an ongoing pregnancy after prolonged GnRH agonist therapy was only 44.4%. Endometrial alpha(v)beta(3) integrin expression did not predict which endometriosis patients would benefit from prolonged GnRHa therapy before IVF. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

[Diagnostic value of immunohistochemistry and FISH for chromosome 12p in type Ⅱ testicular germ cell tumors].

PubMed

Shen, Qin; Rao, Qiu; Yu, Bo; Xia, Qiu-Yuan; Bao, Wei; Lu, Zhen-Feng; Shi, Qun-Li; Zhou, Xiao-Jun

2016-08-01

To study the pathological morphology, immunohistochemical characteristics, and molecular changes of type Ⅱ testicular germ cell tumors (TGCT) and investigate the possible value of immunohistochemistry and fluorescence in situ hybridization (FISH) in the diagnosis of TGCT. We collected for this study 97 cases of TGCT, including 75 cases of seminoma, 17 cases of embryonal carcinoma, 11 cases of yolk sac tumor, 16 cases of mature teratoma, 3 cases of immature teratoma, and 1 case of epidermoid cyst, in which normal testicular tissue was found in 20 and non-TGCT in 6. We detected the expressions of different antibodies in various subtypes of TGCT by immunohistochemistry and determined the rate of chromosome 12p abnormality using FISH. The immunophenotypes varied with different subtypes of TGCT. SALL4 and PLAP exhibited high sensitivity in all histological subtypes. CD117 and OCT4 showed strongly positive expressions in invasive seminoma and germ cell neoplasia in situ (GCNIS) but not in normal seminiferous tubules. GPC3 was significantly expressed in the yolk sac tumor, superior to GATA3 and AFP in both range and intensity. CKpan, OCT4, and CD30 were extensively expressed in embryonal carcinoma, while HCG expressed in choriocarcinoma. The positivity rate of isochromosome 12p and 12p amplification in TGCT was 96.7% (29/30). The majority of TGCT can be diagnosed by histological observation, but immunohistochemical staining is crucial for more accurate subtypes and valuable for selection of individualized treatment options and evaluation of prognosis. Chromosome 12p abnormality is a specific molecular alteration in type Ⅱ TGCT, which is useful for ruling out other lesions.

p16 Expression and Biological Behavior of Flat Vulvar Low-grade Squamous Intraepithelial Lesions (LSIL).

PubMed

Lewis, Natasha; Blanco, Luis Z; Maniar, Kruti P

2017-09-01

Flat low-grade squamous intraepithelial lesion (LSIL) of the vulva [vulvar intraepithelial neoplasia (VIN) 1, flat condyloma] is an uncommon entity with poorly understood biological behavior. We aimed to determine the risk of subsequent vulvar high-grade squamous intraepithelial lesion (HSIL) or carcinoma following a diagnosis of vulvar LSIL/VIN 1, as well as the frequency and predictive value of p16 immunohistochemical expression in this setting. Of the 51 included cases, p16 positivity (diffuse block staining) was identified in 2 (4%). Follow-up data were available in 34 cases, of which 2 (5.9%) developed subsequent vulvar HSIL, including 1/2 p16-positive cases and 1/32 p16-negative cases. The difference in HSIL frequency between p16-positive and p16-negative cases was not statistically significant (P=0.116 for VIN 2+, P=0.061 for VIN 3). For the 18 patients with treatment information available, 10 (56%) received medical or surgical treatment after biopsy. Our results indicate that flat vulvar LSIL is infrequently p16 positive, and that few patients with vulvar LSIL develop subsequent vulvar HSIL. Despite the use of destructive treatment in some cases, the data provide support for the nonpreneoplastic nature of the entity. Immunohistochemical expression of p16 may not be a predictor of HSIL risk in vulvar LSIL, although this result may also be related to the very low rates of both p16 positivity and subsequent vulvar HSIL in our sample. It is clear that vulvar LSIL is distinct from LSIL in other lower anogenital sites in terms of its behavior and p16 expression frequency.

Anticipatory smiling: Linking early affective communication and social outcome

PubMed Central

Parlade, Meaghan Venezia; Messinger, Daniel S.; Delgado, Christine E.F.; Kaiser, Marygrace Yale; Van Hecke, Amy Vaughan; Mundy, Peter C.

2009-01-01

In anticipatory smiles, infants appear to communicate pre-existing positive affect by smiling at an object and then turning the smile toward an adult. We report two studies in which the precursors, development, and consequences of anticipatory smiling were investigated. Study 1 revealed a positive correlation between infant smiling at 6 months and the level of anticipatory smiling at 8 and 10 months during joint attention episodes, as well as a positive correlation between anticipatory smiling and parent-rated social expressivity scores at 30 months. Study 2 confirmed a developmental increase in the number of infants using anticipatory smiles between 9 and 12 months that had been initially documented in the Study 1 sample [Venezia, M., Messinger, D. S., Thorp, D., & Mundy, P. (2004). The development of anticipatory smiling. Infancy, 6(3), 397–406]. Additionally, anticipatory smiling at 9 months positively predicted parent-rated social competence scores at 30 months. Findings are discussed with regard to the importance of anticipatory smiling in early socioemotional development. PMID:19004500

Social anxiety and detection of facial untrustworthiness: Spatio-temporal oculomotor profiles.

PubMed

Gutiérrez-García, Aida; Calvo, Manuel G; Eysenck, Michael W

2018-04-01

Cognitive models posit that social anxiety is associated with biased attention to and interpretation of ambiguous social cues as threatening. We investigated attentional bias (selective early fixation on the eye region) to account for the tendency to distrust ambiguous smiling faces with non-happy eyes (interpretative bias). Eye movements and fixations were recorded while observers viewed video-clips displaying dynamic facial expressions. Low (LSA) and high (HSA) socially anxious undergraduates with clinical levels of anxiety judged expressers' trustworthiness. Social anxiety was unrelated to trustworthiness ratings for faces with congruent happy eyes and a smile, and for neutral expressions. However, social anxiety was associated with reduced trustworthiness rating for faces with an ambiguous smile, when the eyes slightly changed to neutrality, surprise, fear, or anger. Importantly, HSA observers looked earlier and longer at the eye region, whereas LSA observers preferentially looked at the smiling mouth region. This attentional bias in social anxiety generalizes to all the facial expressions, while the interpretative bias is specific for ambiguous faces. Such biases are adaptive, as they facilitate an early detection of expressive incongruences and the recognition of untrustworthy expressers (e.g., with fake smiles), with no false alarms when judging truly happy or neutral faces. Copyright © 2018 Elsevier B.V. All rights reserved.

CD117 expression in operable oesophageal squamous cell carcinomas predicts worse clinical outcome

PubMed Central

Fan, Huijie; Yuan, Yuan; Wang, Junsheng; Zhou, Fuyou; Zhang, Mingzhi; Giercksky, Karl-Erik; Nesland, Jahn M; Suo, Zhenhe

2013-01-01

Aims To investigate the aberrant expression of CD117 in oesophageal squamous cell carcinoma (SCC) and its prognostic significance. Methods and results Immunohistochemical staining for CD117 was performed on tissue microarray and routine tissue sections from 157 oesophageal SCC patients and 10 normal oesophageal epithelia adjacent to tumour. The positive rate of CD117 expression was 29.9% in oesophageal SCC tissues, whereas no CD117 expression was detected in the 10 normal oesophageal epithelia. CD117 expression was significantly associated with T stage (P < 0.001), distant metastasis (P = 0.015), lymph node metastasis (P = 0.019), and clinical stage (P = 0.021). Progression-free survival in the patients with CD117-positive tumours was shorter than that in the patients with CD117-negative tumours (P = 0.010). In univariate analyses, CD117 expression was the most significant factor for overall survival of oesophageal SCC patients (P < 0.001), followed by lymph node metastasis (P = 0.001), T stage (P = 0.002), clinical stage (P = 0.006), distant metastasis (P = 0.020), and histological grade (P = 0.027). Multivariate analyses verified that CD117 expression was an independent prognostic marker for oesophageal SCC patients (P = 0.002). In addition, CD117 expression predicted poorer survival in patients without distant metastases. Conclusions CD117 expression in operable oesophageal SCC may be a valuable prognostic marker, and detection of its expression in clinical samples may be useful in defining a subclass of oesophageal SCCs with extremely poor clinical outcome, which may require a specially targeted treatment modality. PMID:23570416

Correlation between STK33 and the pathology and prognosis of lung cancer

PubMed Central

Lu, Yi; Tang, Jie; Zhang, Wenmei; Shen, Ce; Xu, Ling; Yang, Danrong

2017-01-01

Correlation between the expression of STK33 and the pathology of lung cancer was investigated, to explore its effects on prognosis. Hundred and two lung cancer patients diagnosed by pathological examinations were randomly selected in Shanghai Jiao Tong University Affiliated Sixth People's Hospital from February, 2012 to February, 2017 to serve as observation group, and the tumor tissues were collected. At the same time, 19 patients with lung benign lesions were selected and lung tissues were also collected to serve as control group. RT-qPCR was used to detect the expression of STK33 mRNA in tissues. Expression levels of STK33 protein were detected and compared by SP immunohistochemistry staining and western blot analysis. Statistical analysis was performed to analyze the correlation between STK33 expression and the pathology and prognosis of lung cancer. Results of PCR showed that expression level of STK33 gene in control group was significantly lower than that in observation group (p<0.05). The expression level of STK33 mRNA in lung adenocarcinoma and squamous cell carcinoma was lower than that in lung small cell carcinoma and large cell carcinoma (p<0.05). Western blot analysis showed that the expression level of STK33 protein in lung small cell carcinoma and large cell carcinoma was significantly higher than that in lung adenocarcinoma and squamous cell carcinoma (p<0.05). Immunohistochemistry staining showed that the positive rate of STK33 in lung large cell carcinoma (100%) and small cell carcinoma (100%) was significantly higher than that in lung adenocarcinoma (88.1%) and squamous cell carcinoma (86.2%) (p<0.05). The 5-year survival rate analysis showed that the recurrence-free survival rate and overall survival rate of STK33 gene high expression level group were significantly lower than those of low expression level group (p<0.05). The differential expression level of STK33 is related to the pathology and prognosis of lung cancer, which is of great value in clinical diagnosis and prognosis evaluation. PMID:29085482

The Expression of TaRca2-α Gene Associated with Net Photosynthesis Rate, Biomass and Grain Yield in Bread Wheat (Triticum aestivum L.) under Field Conditions

PubMed Central

Saeed, Iqbal; Bachir, Daoura Goudia; Chen, Liang; Hu, Yin-Gang

2016-01-01

Improvement in activation of Rubisco by Rubisco activase can potentially enhance CO2 assimilation and photosynthetic efficiency in plants. The three homoeologous copies of TaRca2-α were identified on chromosomes 4AL, 4BS and 4DS (TaRca2-α-4AL, TaRca2-α-4BS, and TaRca2-α-4DS) in bread wheat. Expression patterns of the three copies at heading (Z55), anthesis (Z67) and grain-filling (Z73) stages were investigated through qRT-PCR analyses in a panel of 59 bread wheat genotypes and their effects on net photosynthesis rate (Pn), biomass plant-1 (BMPP) and grain yield plant-1 (GYPP) were further explored. Different but similar expression patterns were observed for the three copies of TaRca2-α at the three growth stages with highest expression at grain-filling stage. TaRca2-α-4BS expressed higher at the three stages than TaRca2-α-4AL and TaRca2-α-4DS. The 59 genotypes could be clustered into three groups as high (7 genotypes), intermediate (41 genotypes) and low (11 genotypes) expression based on the expression of the three copies of TaRca2-α at three growth stages. Significant variations (P<0.01) were observed among the three groups of bread wheat genotypes for Pn, BMPP and GYPP. Generally, the genotypes with higher TaRca2-α expression also showed higher values for Pn, BMPP and GYPP. The expressions of the three copies of TaRca2-α at heading, anthesis and grain-filling stages were positively correlated with Pn, BMPP and GYPP (P<0.01) with stronger association for TaRca2-α-4BS at grain-filling stage. These results revealed that the expression of TaRca2-α contribute substantially to Pn, BMPP and GYPP, and suggested that manipulating TaRca-α expression may efficiently improve Pn, BMPP and GYPP in bread wheat and detecting TaRca-α expression levels with emphasis on TaRca2-α-4BS may be a positive strategy for selection in improving photosynthetic efficiency and grain yield of bread wheat. PMID:27548477

Expression pattern of immunosurveillance-related antigen in adult T cell leukaemia/lymphoma.

PubMed

Asano, Naoko; Miyoshi, Hiroaki; Kato, Takeharu; Shimono, Joji; Yoshida, Noriaki; Kurita, Daisuke; Sasaki, Yuya; Kawamoto, Keisuke; Ohshima, Koichi; Seto, Masao

2018-05-01

Adult T cell leukaemia/lymphoma (ATLL) is an aggressive malignancy with a poor prognosis. Human leucocyte antigen (HLA) and β2 microglobulin (β2M) serve as key molecules in tumour immunity, and their expression is reduced frequently in tumour cells. Programmed cell death (PD)-1/PD-ligand1 (PD-L1) interactions play a role in escape of tumour cells from T cell immunity. Therefore, this study aimed to determine the clinicopathological relevance of HLA and β2M expressions in ATLL cells and PD-L1 expression in lymphoma or stromal cells and predict the overall survival of patients with ATLL. We analysed a total of 123 biopsy samples from patients newly diagnosed with ATLL by using immunohistochemical analysis. Of the patients enrolled, 91 (74%) were positive for HLA (in cell membrane, 60 patients), 89 (72%) were positive for β2M (in cell membrane, 54 patients) and 48 (39%) were positive for both HLA and β2M in the cell membrane (HLA m+ β2M m+ ). No significant clinical differences other than prognosis were found between the HLA m+ β2M m+ group and the other groups. Immunophenotypical evaluation revealed significantly higher rates of CD30-positive lymphoma cells (P = 0.003) and PD-L1-positive stromal cells in microenvironments (miPD-L1 high ) (P = 0.011) of the HLA m+ β2M m+ group than in the other groups. The HLA m+ β2M m+ group had a significantly better prognosis that the other groups (P = 0.0096), and patients showing HLA m+ β2M m+ with miPD-L1 high had the most favourable prognosis among all groups. The membranous expression of HLA and β2M is likely to reflect the immune response and would be useful to predict prognosis before starting ATLL therapy. © 2018 John Wiley & Sons Ltd.

The role of EMMPRIN expression in ovarian epithelial carcinomas.

PubMed

Zhao, Yang; Chen, Shuo; Gou, Wen-feng; Niu, Zhe-feng; Zhao, Shuang; Xiao, Li-jun; Takano, Yasuo; Zheng, Hua-chuan

2013-09-01

Extracellular matrix metalloproteinase inducer (EMMPRIN) was reported to involve in the invasion and metastasis of malignancies by regulating the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in stromal and cancer cells. The study aimed to clarify the role of EMMPRIN expression in tumorigenesis and progression of ovarian epithelial carcinomas. EMMPRIN siRNA were transfected into ovarian carcinoma cells with the phenotypes and their related molecules examined. EMMPRIN expression was determined in ovarian normal tissue, benign and borderline tumors, and epithelial carcinomas by real-time PCR, western blot, and immunohistochemistry. EMMPRIN siRNA treatment resulted in a lower growth, G 1 arrest, apoptotic induction, decreased migration, and invasion. The transfectants showed reduced expression of Wnt5a, Akt, p70s6k, Bcl-xL, survivin, VEGF, and MMP-9 than mock and control cells at both mRNA and protein levels. According to real-time PCR and western blot, EMMPRIN mRNA or protein level was higher in ovarian borderline tumor and carcinoma than normal ovary and benign tumors (P<0.05), and positively correlated with dedifferentiation and FIGO staging (P<0.05). Immunohistochemically, EMMPRIN expression was positively correlated with FIGO staging, dedifferentiation, Ki-67 expression, the lower cumulative and relapse-free survival rate (P<0.05). Upregulated expression of EMMPRIN protein and mRNA might be involved in the pathogenesis, differentiation, and progression of ovarian carcinomas, possibly by modulating cellular events, such as proliferation, cell cycle, apoptosis, migration, and invasion.

The role of EMMPRIN expression in ovarian epithelial carcinomas

PubMed Central

Zhao, Yang; Chen, Shuo; Gou, Wen-feng; Niu, Zhe-feng; Zhao, Shuang; Xiao, Li-jun; Takano, Yasuo; Zheng, Hua-chuan

2013-01-01

Purpose: Extracellular matrix metalloproteinase inducer (EMMPRIN) was reported to involve in the invasion and metastasis of malignancies by regulating the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in stromal and cancer cells. The study aimed to clarify the role of EMMPRIN expression in tumorigenesis and progression of ovarian epithelial carcinomas. Methods: EMMPRIN siRNA were transfected into ovarian carcinoma cells with the phenotypes and their related molecules examined. EMMPRIN expression was determined in ovarian normal tissue, benign and borderline tumors, and epithelial carcinomas by real-time PCR, western blot, and immunohistochemisty. Results: EMMPRIN siRNA treatment resulted in a lower growth, G1 arrest, apoptotic induction, decreased migration, and invasion. The transfectants showed reduced expression of Wnt5a, Akt, p70s6k, Bcl-xL, survivin, VEGF, and MMP-9 than mock and control cells at both mRNA and protein levels. According to real-time PCR and western blot, EMMPRIN mRNA or protein level was higher in ovarian borderline tumor and carcinoma than normal ovary and benign tumors (P < 0.05), and positively correlated with dedifferentiation and FIGO staging (P < 0.05). Immuhistochemically, EMMPRIN expression was positively correlated with FIGO staging, dedifferentiation, Ki-67 expression, the lower cumulative and relapse-free survival rate (P < 0.05). Conclusions: Upregulated expression of EMMPRIN protein and mRNA might be involved in the pathogenesis, differentiation, and progression of ovarian carcinomas, possibly by modulating cellular events, such as proliferation, cell cycle, apoptosis, migration, and invasion. PMID:23966157

Impairment of vocal expression of negative emotions in patients with Alzheimer's disease.

PubMed

Han, Kyung-Hun; Zaytseva, Yuliya; Bao, Yan; Pöppel, Ernst; Chung, Sun Yong; Kim, Jong Woo; Kim, Hyun Taek

2014-01-01

Vocal expression of emotions (EE) in retrieval of events from autobiographical memory was investigated in patients in early stages of Alzheimer's disease (AD). Twenty-one AD patients and 19 controls were interviewed, and EE of the reported memories was rated by 8 independent evaluators. The AD group had lower EE of both recent and remote memory than controls, although EE in remote memories was better preserved in both groups. We observed positive correlations between EE and indicators of cognitive competence in AD patients. AD Patients are impaired in the ability to express emotions already at early stages of the disease, and EE seems to deteriorate along with the progression of cognitive impairment.

A robust variable sampling time BLDC motor control design based upon μ-synthesis.

PubMed

Hung, Chung-Wen; Yen, Jia-Yush

2013-01-01

The variable sampling rate system is encountered in many applications. When the speed information is derived from the position marks along the trajectory, one would have a speed dependent sampling rate system. The conventional fixed or multisampling rate system theory may not work in these cases because the system dynamics include the uncertainties which resulted from the variable sampling rate. This paper derived a convenient expression for the speed dependent sampling rate system. The varying sampling rate effect is then translated into multiplicative uncertainties to the system. The design then uses the popular μ-synthesis process to achieve a robust performance controller design. The implementation on a BLDC motor demonstrates the effectiveness of the design approach.

A Robust Variable Sampling Time BLDC Motor Control Design Based upon μ-Synthesis

PubMed Central

Yen, Jia-Yush

2013-01-01

The variable sampling rate system is encountered in many applications. When the speed information is derived from the position marks along the trajectory, one would have a speed dependent sampling rate system. The conventional fixed or multisampling rate system theory may not work in these cases because the system dynamics include the uncertainties which resulted from the variable sampling rate. This paper derived a convenient expression for the speed dependent sampling rate system. The varying sampling rate effect is then translated into multiplicative uncertainties to the system. The design then uses the popular μ-synthesis process to achieve a robust performance controller design. The implementation on a BLDC motor demonstrates the effectiveness of the design approach. PMID:24327804

Forming impressions: effects of facial expression and gender stereotypes.

PubMed

Hack, Tay

2014-04-01

The present study of 138 participants explored how facial expressions and gender stereotypes influence impressions. It was predicted that images of smiling women would be evaluated more favorably on traits reflecting warmth, and that images of non-smiling men would be evaluated more favorably on traits reflecting competence. As predicted, smiling female faces were rated as more warm; however, contrary to prediction, perceived competence of male faces was not affected by facial expression. Participants' female stereotype endorsement was a significant predictor for evaluations of female faces; those who ascribed more strongly to traditional female stereotypes reported the most positive impressions of female faces displaying a smiling expression. However, a similar effect was not found for images of men; endorsement of traditional male stereotypes did not predict participants' impressions of male faces.

Balance in Positive Emotional Expressivity across School Contexts Relates to Kindergartners' Adjustment

ERIC Educational Resources Information Center

Hernández, Maciel M.; Eisenberg, Nancy; Valiente, Carlos; Spinrad, Tracy L.; Berger, Rebecca H.; VanSchyndel, Sarah K.; Thompson, Marilyn S.; Southworth, Jody; Silva, Kassondra M.

2018-01-01

Positive emotional expressivity has been associated with increased social competence and decreased maladjustment in childhood. However, a few researchers have found null or even positive associations between positive emotional expressivity and maladjustment, which suggests that there may be nuanced associations of positive expressivity, perhaps as…

Detection of pAkt protein in imprint cytology of invasive breast cancer: Correlation with HER2/neu, hormone receptors, and other clinicopathological variables.

PubMed

Vasou, Olympia; Skagias, Lazaros; Anastasia, Margariti; Paulina, Athanasiadou; Patsouris, Efstratios; Politi, Ekaterini

2015-01-01

Akt is a serine/threonine protein kinase and has emerged as a crucial regulator of widely divergent cellular processes, including apoptosis, proliferation, differentiation, and metabolism. Activation of Akt/protein kinase B has been positively associated with human epidermal growth-factor receptor 2 (HER2)/neu overexpression in breast carcinoma and a worse outcome among endocrine treated patients. The Akt signaling pathway currently attracts considerable attention as a new target for effective therapeutic strategies. We therefore investigated the relationship between activation of Akt and clinicopathologic variables including hormone receptor and HER2/neu status. Archival tumor tissues from 100 patients with invasive breast carcinoma were analyzed by immunocytochemistry. This study describes the results of immunocytochemical pAkt expression in breast carcinoma imprints, prepared from cut surfaces of freshly removed tumors. Both nuclear and cytoplasmic expressions were evaluated for pAkt. Nuclear and cytoplasmic positive scores of 72% (72/100) and 42% (42/100), respectively, were found. Coexistence of nuclear and cytoplasmic staining was observed in 32 cases (32/100). Nuclear positive staining correlated with HER2/neu overexpression (P = 0.043) and was significantly associated with positive involvement of axillary lymph nodes (P = 0.013). No correlation was found between cytoplasmic pAkt rate and clinicopathological parameters, estrogen receptor, progesterone receptor or HER2/neu expression. pAkt expression can be evaluated in cytological material and may add valuable information to current prognostic models for breast cancer. pAkt overexpression appears to be linked with potentially aggressive tumor phenotype in invasive breast carcinoma.

Expression of GLUT-1 glucose transporter in borderline and malignant epithelial tumors of the ovary.

PubMed

Cantuaria, G; Magalhaes, A; Penalver, M; Angioli, R; Braunschweiger, P; Gomez-Marin, O; Kanhoush, R; Gomez-Fernandez, C; Nadji, M

2000-10-01

Cancer cells have increased rates of glucose metabolism when compared to normal cells. One of the mechanisms proposed for the accelerated glucose use in malignant cells is the overexpression of glucose transporters. In this study we evaluated the expression of the GLUT-1 glucose transporter in borderline and malignant epithelial neoplasms of the ovary. Histologic sections of tumor tissues from 21 borderline and 82 malignant epithelial neoplasms of the ovary were stained for GLUT-1 using polyclonal GLUT-1 antibody (Dako, Carpinteria, CA) and the labeled streptavidin biotin procedure. DAB was used as chromagen and tissues were counterstained with hematoxylin. Normal ovarian surface epithelial cells were either negative or weakly positive. Of the 82 carcinomas, 81 (98.8%) were positive for GLUT-1. The staining intensity was significantly associated with the grade of tumor (P = 0.001). Of the 21 borderline neoplasms, 20 (95.2%) were positive for GLUT-1. Carcinomas had a significantly stronger stain than borderline tumors (P = 0.0001). The intensity of the stain was also stronger in serous carcinomas compared to other subtypes (P = 0. 0001). Positive cells demonstrated a cytoplasmic membrane staining that was more intense in tumor cells farther away from blood supply. Overexpression of the GLUT-1 transporter is associated with the histology and grade of the tumors. Our findings show a progressive increase in the expression of the GLUT-1 transporter from the borderline tumor to the high-grade carcinomas. These data suggest that the expression of this transporter may be closely related to the malignant transformation of epithelial ovarian tumors. Copyright 2000 Academic Press.

Effect of sperm entry on blastocyst development after in vitro fertilization and intracytoplasmic sperm injection - mouse model.

PubMed

Piotrowska-Nitsche, Karolina; Chan, Anthony W S

2013-01-01

To investigate whether in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), influence the embryo's development and its quality using the mouse as a model. Assisted fertilization was performed using ICSI and IVF. Fluorescent beads were adhered to the fertilization cone or place of previous sperm injection in the natural mated (NM), IVF and ICSI embryos, respectively. Embryo examination was carried out at the two-cell and blastocyst stage to determine the position of fluorescent bead. Protein expression was detected by fluorescence immunocytochemical staining and confocal microscopic imaging of blastocysts. IVF and ICSI embryos developed at rates comparable to NM group. Embryos show similar expression patterns of two transcription factors, Oct4 and Cdx2. The most preferred place for spermatozoa attachment was the equatorial site of the egg, whether fertilization occurred in vitro or under natural conditions. We also link the sperm entry position (SEP) to embryo morphology and the number of cells at the blastocyst stage, with no influence of the method of fertilization. IVF and ICSI, do not compromise in vitro pre-implantation development. Additional data, related to sperm entry, could offer further criteria to predict embryos that will implant successfully. Based on embryo morphology, developmental rate and protein expression level of key transcription factors, our results support the view that ART techniques, such as IVF and ICSI, do not perturb embryonic development or quality.

Expression of emotions and physiological changes during teaching

NASA Astrophysics Data System (ADS)

Tobin, Kenneth; King, Donna; Henderson, Senka; Bellocchi, Alberto; Ritchie, Stephen M.

2016-09-01

We investigated the expression of emotions while teaching in relation to a teacher's physiological changes. We used polyvagal theory (PVT) to frame the study of teaching in a teacher education program. Donna, a teacher-researcher, experienced high levels of stress and anxiety prior to beginning to teach and throughout the lesson we used her expressed emotions as a focus for this research. We adopted event-oriented inquiry in a study of heart rate, oxygenation of the blood, and expressed emotions. Five events were identified for multilevel analysis in which we used narrative, prosodic analysis, and hermeneutic-phenomenological methods to learn more about the expression of emotions when Donna had: high heart rate (before and while teaching); low blood oxygenation (before and while teaching); and high blood oxygenation (while teaching). What we learned was consistent with the body's monitoring system recognizing social harm and switching to the control of the unmyelinated vagus nerve, thereby shutting down organs and muscles associated with social communication—leading to irregularities in prosody and expression of emotion. In events involving high heart rate and low blood oxygenation the physiological environment was associated with less effective and sometimes confusing patterns in prosody, including intonation, pace of speaking, and pausing. In a low blood oxygenation environment there was evidence of rapid speech and shallow, irregular breathing. In contrast, during an event in which 100 % blood oxygenation occurred, prosody was perceived to be conducive to engagement and teacher expressed positive emotions, such as satisfaction, while teaching. Becoming aware of the purposes of the research and the results we obtained provided the teacher with tools to enact changes to her teaching practice, especially prosody of the voice. We regard it as a high priority to create tools to allow teachers and students, if and as necessary, to ameliorate excess emotions, and change heart rate, oxygenation levels, and breathing patterns.

Functional regression method for whole genome eQTL epistasis analysis with sequencing data.

PubMed

Xu, Kelin; Jin, Li; Xiong, Momiao

2017-05-18

Epistasis plays an essential rule in understanding the regulation mechanisms and is an essential component of the genetic architecture of the gene expressions. However, interaction analysis of gene expressions remains fundamentally unexplored due to great computational challenges and data availability. Due to variation in splicing, transcription start sites, polyadenylation sites, post-transcriptional RNA editing across the entire gene, and transcription rates of the cells, RNA-seq measurements generate large expression variability and collectively create the observed position level read count curves. A single number for measuring gene expression which is widely used for microarray measured gene expression analysis is highly unlikely to sufficiently account for large expression variation across the gene. Simultaneously analyzing epistatic architecture using the RNA-seq and whole genome sequencing (WGS) data poses enormous challenges. We develop a nonlinear functional regression model (FRGM) with functional responses where the position-level read counts within a gene are taken as a function of genomic position, and functional predictors where genotype profiles are viewed as a function of genomic position, for epistasis analysis with RNA-seq data. Instead of testing the interaction of all possible pair-wises SNPs, the FRGM takes a gene as a basic unit for epistasis analysis, which tests for the interaction of all possible pairs of genes and use all the information that can be accessed to collectively test interaction between all possible pairs of SNPs within two genome regions. By large-scale simulations, we demonstrate that the proposed FRGM for epistasis analysis can achieve the correct type 1 error and has higher power to detect the interactions between genes than the existing methods. The proposed methods are applied to the RNA-seq and WGS data from the 1000 Genome Project. The numbers of pairs of significantly interacting genes after Bonferroni correction identified using FRGM, RPKM and DESeq were 16,2361, 260 and 51, respectively, from the 350 European samples. The proposed FRGM for epistasis analysis of RNA-seq can capture isoform and position-level information and will have a broad application. Both simulations and real data analysis highlight the potential for the FRGM to be a good choice of the epistatic analysis with sequencing data.

Enhancement or inhibition of PLCγ2 expression in rat hepatocytes by recombinant adenoviral vectors that contain full-length gene or siRNA.

PubMed

Chen, X G; Liu, Y M; Lv, Q X; Ma, J

2017-01-01

We investigated the effects of recombinant adenovirus vectors that overexpress or silence PLCγ2 on the expression of this gene during hepatocyte proliferation. Hepatocytes were isolated, identified by immunofluorescent cytochemical staining and infected by previously constructed Ad-PLCγ2 and Ad-PLCγ2 siRNA1, siRNA2 and siRNA3. Green fluorescent protein (GFP) expression was observed by fluorescence microscopy. Infection percentage was calculated by flow cytometry. mRNA and protein levels of PLCγ2 were detected by quantitative reverse transcription-PCR (qRT-PCR) and western blotting, respectively. The viability of the infected hepatocytes was measured by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. We found that nearly 97% of cells were positive for the hepatocyte marker, CK18. After infection of Ad-PLCγ2 and Ad-PLCγ2 siRNA, more than 99% of hepatocytes expressed GFP significantly, and mRNA and protein expression of PLCγ2 was up-regulated significantly in Ad-PLCγ2 infected hepatocytes, but down-regulated in Ad-PLCγ2 siRNA2 infected cells. The cell proliferation rate decreased in PLCγ2-overexpressing cells, while the rate increased in PLCγ2-silencing cells. We verified that recombinant Ad-PLCγ2 and Ad-PLCγ2 siRNA2 were constructed successfully. These two recombinant vectors promoted or decreased the expression of PLCγ2 in rat hepatocytes and affected the cell proliferation rate, which provides a useful tool for further investigation of the role of PLCγ2 in hepatocyte apoptosis.

Prognostic relevance of proliferation markers (Ki-67, PHH3) within the cross-relation of ERG translocation and androgen receptor expression in prostate cancer.

PubMed

Goltz, Diane; Montani, Matteo; Braun, Martin; Perner, Sven; Wernert, Nicolas; Jung, Klaus; Dietel, Manfred; Stephan, Carsten; Kristiansen, Glen

2015-12-01

We evaluated the prognostic value of the mitosis-associated marker phosphorylated histone H3 (PHH3) and Ki-67 in prostate cancer with respect to ERG status and androgen receptor (AR) expression.PHH3 and Ki-67 expression was immunohistochemically detected and digitally quantitated in a radical prostatectomy cohort (n = 640). The results were correlated to clinicopathological parameters including biochemical recurrence times. Prognostic values of PHH3 and Ki-67 were analysed by Cox regression and Kaplan-Meier statistics.In prostate cancer, mean Ki-67 and PHH3 rates were 3.40% (95%CI 3.16-3.63%) and 0.0152% (95%CI 0.0112-0.0191%), respectively.Ki-67 showed a significant correlation with Gleason scores, pT status, margin status, and AR expression, while PHH3 showed a significant correlation with Gleason scores and pT status. Univariate analyses for biochemical recurrence times demonstrated a significant prognostic value for median Ki-67 rate and for the PHH3 rate of the 90th percentile. Of importance, in patient subgroups stratified according to AR expression and ERG translocation, the prognostic power of proliferation markers PHH3 and Ki-67 was markedly enhanced in ERG translocation negative and high-level AR expressing ERG translocation positive prostate cancers.As expected, the proliferation markers PHH3 and Ki-67 predict adverse outcome of prostate cancer and have a particularly pronounced prognostic value in specific molecular subsets of prostate cancer (ERG- or AR+).

Overexpression of stathmin1 in the diffuse type of gastric cancer and its roles in proliferation and migration of gastric cancer cells.

PubMed

Jeon, T-Y; Han, M-E; Lee, Y-W; Lee, Y-S; Kim, G-H; Song, G-A; Hur, G-Y; Kim, J-Y; Kim, H-J; Yoon, S; Baek, S-Y; Kim, B-S; Kim, J-B; Oh, S-O

2010-02-16

Stathmin1 is a microtubule-regulating protein that has an important role in the assembly and disassembly of the mitotic spindle. The roles of stathmin1 in carcinogenesis of various cancers, including prostate and breast cancer, have been explored. However, its expression and roles in gastric cancer have not yet been described. Stathmin1 expression in paraffin-embedded tissue sections from 226 patients was analysed by immunohistochemistry. Roles of stathmin1 were studied using a specific small interfering RNA (siRNA). The expression of stathmin1 was positively correlated with lymph node metastasis, TNM stages and vascular invasion, and negatively with recurrence-free survival, in the diffuse type of gastric cancer. The median recurrence-free survival in patients with a negative and positive expression of stathmin1 was 17.0 and 7.0 months, respectively (P=0.009). When the expression of stathmin1 was knocked down using siRNA, the proliferation, migration and invasion of poorly differentiated gastric cancer cells in vitro were significantly inhibited. Moreover, stathmin1 siRNA transfection significantly slowed the growth of xenografts in nude mice. These results suggest that stathmin1 can be a good prognostic factor for recurrence-free survival rate and is a therapeutic target in diffuse-type gastric cancer.

Enhanced radiosensitivity and radiation-induced apoptosis in glioma CD133-positive cells by knockdown of SirT1 expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, C.-J.; Hsu, C.-C.; Department of Surgery, Chi-Mei Medical Center, Taipei, Taiwan

2009-03-06

CD133-expressing glioma cells play a critical role in tumor recovery after treatment and are resistant to radiotherapy. Herein, we demonstrated that glioblastoma-derived CD133-positive cells (GBM-CD133{sup +}) are capable of self-renewal and express high levels of embryonic stem cell genes and SirT1 compared to GBM-CD133{sup -} cells. To evaluate the role of SirT1 in GBM-CD133{sup +}, we used a lentiviral vector expressing shRNA to knock-down SirT1 expression (sh-SirT1) in GBM-CD133{sup +}. Silencing of SirT1 significantly enhanced the sensitivity of GBM-CD133{sup +} to radiation and increased the level of radiation-mediated apoptosis. Importantly, knock-down of SirT1 increased the effectiveness of radiotherapy in themore » inhibition of tumor growth in nude mice transplanted with GBM-CD133{sup +}. Kaplan-Meier survival analysis indicated that the mean survival rate of GBM-CD133{sup +} mice treated with radiotherapy was significantly improved by Sh-SirT1 as well. In sum, these results suggest that SirT1 is a potential target for increasing the sensitivity of GBM and glioblastoma-associated cancer stem cells to radiotherapy.« less

Mammalian keratin associated proteins (KRTAPs) subgenomes: disentangling hair diversity and adaptation to terrestrial and aquatic environments.

PubMed

Khan, Imran; Maldonado, Emanuel; Vasconcelos, Vítor; O'Brien, Stephen J; Johnson, Warren E; Antunes, Agostinho

2014-09-10

Adaptation of mammals to terrestrial life was facilitated by the unique vertebrate trait of body hair, which occurs in a range of morphological patterns. Keratin associated proteins (KRTAPs), the major structural hair shaft proteins, are largely responsible for hair variation. We exhaustively characterized the KRTAP gene family in 22 mammalian genomes, confirming the existence of 30 KRTAP subfamilies evolving at different rates with varying degrees of diversification and homogenization. Within the two major classes of KRTAPs, the high cysteine (HS) subfamily experienced strong concerted evolution, high rates of gene conversion/recombination and high GC content. In contrast, high glycine-tyrosine (HGT) KRTAPs showed evidence of positive selection and low rates of gene conversion/recombination. Species with more hair and of higher complexity tended to have more KRATP genes (gene expansion). The sloth, with long and coarse hair, had the most KRTAP genes (175 with 141 being intact). By contrast, the "hairless" dolphin had 35 KRTAPs and the highest pseudogenization rate (74% relative to the 19% mammalian average). Unique hair-related phenotypes, such as scales (armadillo) and spines (hedgehog), were correlated with changes in KRTAPs. Gene expression variation probably also influences hair diversification patterns, for example human have an identical KRTAP repertoire as apes, but much less hair. We hypothesize that differences in KRTAP gene repertoire and gene expression, together with distinct rates of gene conversion/recombination, pseudogenization and positive selection, are likely responsible for micro and macro-phenotypic hair diversification among mammals in response to adaptations to ecological pressures.

The mucin expression profile of endometrial carcinoma and correlation with clinical-pathologic parameters.

PubMed

Morrison, Carl; Merati, Kambiz; Marsh, William L; De Lott, Lindsey; Cohn, David E; Young, Gregory; Frankel, Wendy L

2007-12-01

Mucin expression patterns have been studied in tumors from various sites. Previous studies have shown an association of MUC1 with poor prognosis and MUC2 and MUC5AC with a mucinous phenotype. The pattern of mucin expression in endometrial carcinomas has not been documented in a large series. We determined the mucin expression profile in endometrial carcinomas and evaluated the relationship between mucin expression and clinical-pathologic parameters. A tissue microarray of 310 cases of endometrial carcinoma with known clinical outcome was constructed from formalin-fixed, paraffin-embedded donor blocks using two 0.6 mm cores from each tumor. Sections were stained with monoclonal antibodies against MUC1, MUC2, MUC4, MUC5AC, and MUC6. Staining was considered positive if greater than or equal to 5% of cells stained positively in either core. Mucin expression was correlated with tumor type, histologic grade, International Federation Gynecology and Obstetrics stage, lymph node involvement, depth of myometrial invasion, patient age, ethnicity, and clinical outcome. MUC1 was expressed in 267/310 (86.1%) of endometrial carcinomas, MUC2 in 2/310 (0.6%), MUC4 in 73/310 (23.5%), MUC5AC in 1/310 (0.3%), and MUC6 in 4/310 (1.2%). Endometrioid endometrial carcinoma showed a higher rate of MUC1 expression than nonendometrioid endometrial carcinoma (227/258, 88.0% vs. 39/52, 75.0%, P=0.01). No significant differences in any of the mucins were noted among the other end points evaluated. Mucin expression did not correlate with tumor grade, stage, or patient outcome.

Significance of Cox-2 expression in rectal cancers with or without preoperative radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pachkoria, Ketevan; Zhang Hong; Adell, Gunnar

2005-11-01

Purpose: Radiotherapy has reduced local recurrence of rectal cancers, but the result is not satisfactory. Further biologic factors are needed to identify patients for more effective radiotherapy. Our aims were to investigate the relationship of cyclooxygenase-2 (Cox-2) expression to radiotherapy, and clinicopathologic/biologic variables in rectal cancers with or without radiotherapy. Methods and Materials: Cox-2 expression was immunohistochemically examined in distal normal mucosa (n = 28), in adjacent normal mucosa (n = 107), in primary cancer (n = 138), lymph node metastasis (n = 30), and biopsy (n = 85). The patients participated in a rectal cancer trial of preoperative radiotherapy.more » Results: Cox-2 expression was increased in primary tumor compared with normal mucosa (p < 0.0001), but there was no significant change between primary tumor and metastasis. Cox-2 positivity was or tended to be related to more p53 and Ki-67 expression, and less apoptosis (p {<=} 0.05). In Cox-2-negative cases of either biopsy (p = 0.01) or surgical samples (p = 0.02), radiotherapy was related to less frequency of local recurrence, but this was not the case in Cox-2-positive cases. Conclusion: Cox-2 expression seemed to be an early event involved in rectal cancer development. Radiotherapy might reduce a rate of local recurrence in the patients with Cox-2 weakly stained tumors, but not in those with Cox-2 strongly stained tumors.« less

Matrix metalloproteinase-9 expression correlated with tumor response in patients with locally advanced rectal cancer undergoing preoperative chemoradiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Unsal, Diclehan; Uner, Aytug; Akyurek, Nalan

2007-01-01

Purpose: To analyze whether the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors are associated with tumor response to preoperative chemoradiotherapy in rectal cancer patients. Methods and Materials: Forty-four patients who had undergone preoperative chemoradiotherapy were evaluated retrospectively. Treatment consisted of pelvic radiotherapy and two cycles of 5-fluorouracil plus leucovorin. Surgery was performed 6-8 weeks later. MMP-2, MMP-9, and tissue inhibitors of metalloproteinase-1 and -2 expression was analyzed by immunohistochemistry of the preradiation biopsy and surgical specimens. The intensity and extent of staining were evaluated separately, and a final score was calculated by multiplying the two scores. The primarymore » endpoint was the correlation of expression with tumor response, with the secondary endpoint the effect of chemoradiotherapy on the expression. Results: Preoperative treatment resulted in downstaging in 20 patients (45%) and no clinical response in 24 (55%). The pathologic tumor response was complete in 11 patients (25%), partial in 23 (52%), and none in 10 (23%). Positive MMP-9 staining was observed in 20 tumors (45%) and was associated with the clinical nodal stage (p = 0.035) and the pathologic and clinical response (p < 0.0001). The staining status of the other markers was associated with neither stage nor response. The overall pathologic response rate was 25% in MMP-9-positive patients vs. 52% in MMP-9-negative patients (p = 0.001). None of the 11 patients with pathologic complete remission was MMP-9 positive. Conclusions: Matrix metalloproteinase-9 expression correlated with a poor tumor response to preoperative chemoradiotherapy in rectal carcinoma patients.« less

Long-Lasting Effects of Subliminal Affective Priming from Facial Expressions

PubMed Central

Sweeny, Timothy D.; Grabowecky, Marcia; Suzuki, Satoru; Paller, Ken A.

2009-01-01

Unconscious processing of stimuli with emotional content can bias affective judgments. Is this subliminal affective priming merely a transient phenomenon manifested in fleeting perceptual changes, or are long-lasting effects also induced? To address this question, we investigated memory for surprise faces 24 hours after they had been shown with 30-ms fearful, happy, or neutral faces. Surprise faces subliminally primed by happy faces were initially rated as more positive, and were later remembered better, than those primed by fearful or neutral faces. Participants likely to have processed primes supraliminally did not respond differentially as a function of expression. These results converge with findings showing memory advantages with happy expressions, though here the expressions were displayed on the face of a different person, perceived subliminally, and not present at test. We conclude that behavioral biases induced by masked emotional expressions are not ephemeral, but rather can last at least 24 hours. PMID:19695907

Long-lasting effects of subliminal affective priming from facial expressions.

PubMed

Sweeny, Timothy D; Grabowecky, Marcia; Suzuki, Satoru; Paller, Ken A

2009-12-01

Unconscious processing of stimuli with emotional content can bias affective judgments. Is this subliminal affective priming merely a transient phenomenon manifested in fleeting perceptual changes, or are long-lasting effects also induced? To address this question, we investigated memory for surprise faces 24 h after they had been shown with 30-ms fearful, happy, or neutral faces. Surprise faces subliminally primed by happy faces were initially rated as more positive, and were later remembered better, than those primed by fearful or neutral faces. Participants likely to have processed primes supraliminally did not respond differentially as a function of expression. These results converge with findings showing memory advantages with happy expressions, though here the expressions were displayed on the face of a different person, perceived subliminally, and not present at test. We conclude that behavioral biases induced by masked emotional expressions are not ephemeral, but rather can last at least 24 h.

Effect of the absolute statistic on gene-sampling gene-set analysis methods.

PubMed

Nam, Dougu

2017-06-01

Gene-set enrichment analysis and its modified versions have commonly been used for identifying altered functions or pathways in disease from microarray data. In particular, the simple gene-sampling gene-set analysis methods have been heavily used for datasets with only a few sample replicates. The biggest problem with this approach is the highly inflated false-positive rate. In this paper, the effect of absolute gene statistic on gene-sampling gene-set analysis methods is systematically investigated. Thus far, the absolute gene statistic has merely been regarded as a supplementary method for capturing the bidirectional changes in each gene set. Here, it is shown that incorporating the absolute gene statistic in gene-sampling gene-set analysis substantially reduces the false-positive rate and improves the overall discriminatory ability. Its effect was investigated by power, false-positive rate, and receiver operating curve for a number of simulated and real datasets. The performances of gene-set analysis methods in one-tailed (genome-wide association study) and two-tailed (gene expression data) tests were also compared and discussed.

[Mucoepidermoid carcinoma of salivary glands: the prognostic value of tumoral markers].

PubMed

Hoyek-Gebeily, J; Nehmé, E; Aftimos, G; Sader-Ghorra, C; Sargi, Z; Haddad, A

2007-12-01

Mucoepidermoid carcinoma is one of the most frequent malignant lesions of salivary glands. The treatment is based on clinical, paraclinical and histological data. Several studies on the prognostic value of molecular markers for these cancers were made with contradictory results. The aim of this retrospective study was to analyze the prognostic value of molecular markers of salivary gland mucoepidermoid carcinoma. Sixteen patients were treated for mucoepidermoid carcinoma of principal and/or accessory salivary glands between 1994 and 2003. An immunohistochemical study of archive specimen was performed. Nine markers were specifically studied: 4 proteins/oncoproteins (p53, bcl2, c-erb-B2 and cd117), 2 markers of proliferation (PCNA and Ki67), 1 growing factor receptor (EGFR), 1 epithelial adhesion molecule (E-cadherin), and 1 angiogenic cytokine (PDGF). Nine men and 7 women were included, with a mean age of 43.7 years (14-80). The mean diameter of tumors was 3.1 mm (1-14), and the parotid gland was the most frequent location. The mean global survival rate was 57.3 months with a median of 55 months. The 2 to 5 years survival expectation rate were 82.5% and 46.4% respectively. The mean survival rate for women was superior to that of men (P=0.043). The expression of p53 and the high expression rate of EFGR were bad prognostic factors (respectively P=0.049 and P=0.012). The expression of PCNA was linked to the location (mainly the salivary gland) and to the diameter of the tumor (respectively P=0.037 and P=0.029). The degree of EFGR positivity and the histological grade were linked (P=0.027). The strong expression of EGFR was statistically linked to the histological tumor grade. The degree of PCNA positivity seemed to be associated to the preferential location in the main salivary glands and to the diameter of the tumor. The strong expression of p53 and EGFR were bad prognostic factors. These retrospective results need to be confirmed by prospective randomized and larger studies. EGFR and p53 were significant negative prognostic factors. EGFR was highly correlated to the histological grade, making it an interesting target for further investigation.

[The Influence of New Medium with RGD on Cell Growth,Cell Fusion and Expression of Exogenous Gene].

PubMed

Wang, Pei-Pei; Wei, Da-Peng; Zhu, Tong-Bo

2018-03-01

To investigate the influence of a new culture medium added with RGD on cell growth,cell fusion and expression of exogenous gene. A new medium was prepared by adding different concentrations of RGD to ordinary culture medium. The optimum concentration of RGD was determined by observation of the growth of human pancreatic epithelial cell line HPDE6-C7. After determining the optimum concentration of RGD,different concentrations of cells HPDE6-C7 (5×10 4 ,10 5 ,5×10 5 mL －1 ) were inoculated in the two mediums. The morphology,adherence,growth and density of the cells were observed by inverted microscope; The ratio of clone formation and the positive rate of cloning were compared between the two cultures after fusion; The fluorescence intensity after the transfection of plasmid with green fluorescent protein ( GFP ) and the protein expression after transfection of plasmid with KRAS were observed to campare the expression of exogenous genes between the new medium with ordinary medium. Firstly,the optimal concentration of RGD was 10 ng/mL. Compared with the normal medium,the cultured cells with RGD had better morphology,adhesion and faster proliferation. In addition,both of the number and positive rate of clones formed in the new medium were significantly higher than that in the ordinary medium ( P <0.05);The fluorescence intensity after transfection of exogenous gene GFP in the new medium was significantly higher than that in normal medium ( P <0.05); Expression level of exogenous gene KRAS of the new medium was also significantly higher than that in normal medium. The new culture medium has highlighted advantages in cell growth,cell fusion and expression of exogenous genes. RGD peptide has widely prospect and potential value in the cell culture. Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).

Clinical significance of calcium-binding protein S100A8 and S100A9 expression in non-small cell lung cancer.

PubMed

Huang, He; Huang, Qingdong; Tang, Tingyu; Gu, Liang; Du, Jianzong; Li, Zhijun; Lu, Xiaoling; Zhou, Xiaoxi

2018-05-07

The purpose of this study was to evaluate the correlation between calcium-binding protein S100A8 and S100A9 expression in non-small cell lung cancer (NSCLC) and patients' clinical features. Fifty-two NSCLC patients who underwent surgery at Zhejiang Hospital from February 2014 to January 2016 were included in this study. Calcium-binding protein S100A8 and S100A9 expression patterns in cancer and para-cancer tissues were examined by immunohistochemistry assay. The correlation between calcium-binding protein S100A8 and S100A9 expression patterns and NSCLC patients' clinical characteristics, including age, gender, tumor node metastasis stage, and pathology type, were evaluated. S100A8 and S100A9 were generally expressed on the cytoplasm and nucleus of NSCLC cells, mainly located in the cytoplasm, stained with brown particles, and distributed evenly. The positive expression rates of S100A8 and S100A9 in cancer tissues were 71.2% and 76.9%, respectively, which were significantly higher than in para-cancer tissues at 11.5% and 19.2%, respectively, with statistical significance (P < 0.05). S100A8 and S100A9 positive expression was associated with tumor differentiation degree (P < 0.05) but were not correlated with age, gender, smoking history, tumor diameter, pathology type, tumor node metastasis stage, or pleural effusion (P all  > 0.05). S100A8 and S100A9 positive expression in cancer tissues was significantly higher than in para-cancer tissues and was correlated with tumor differentiation, which may be a potential marker for poor prognosis. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Dimorphous expressions of positive emotion: displays of both care and aggression in response to cute stimuli.

PubMed

Aragón, Oriana R; Clark, Margaret S; Dyer, Rebecca L; Bargh, John A

2015-03-01

Extremely positive experiences, and positive appraisals thereof, produce intense positive emotions that often generate both positive expressions (e.g., smiles) and expressions normatively reserved for negative emotions (e.g., tears). We developed a definition of these dimorphous expressions and tested the proposal that their function is to regulate emotions. We showed that individuals who express emotions in this dimorphous manner do so as a general response across a variety of emotionally provoking situations, which suggests that these expressions are responses to intense positive emotion rather than unique to one particular situation. We used cute stimuli (an elicitor of positive emotion) to demonstrate both the existence of these dimorphous expressions and to provide preliminary evidence of their function as regulators of emotion. © The Author(s) 2015.

Effects of electromagnetic pulse on polydactyly of mouse fetuses.

PubMed

Yang, Ming-Juan; Liu, Jun-Ye; Wang, Ya-Feng; Lang, Hai-Yang; Miao, Xia; Zhang, Li-Yan; Zeng, Li-Hua; Guo, Guo-Zhen

2013-07-01

There is an increasing public concern regarding potential health impacts from electromagnetic radiation exposure. Embryonic development is sensitive to the external environment, and limb development is vital for life quality. To determine the effects of electromagnetic pulse (EMP) on polydactyly of mouse fetuses, pregnant mice were sham-exposed or exposed to EMP (400 kV/m with 400 pulses) from Days 7 to 10 of pregnancy (Day 0 = day of detection of vaginal plug). As a positive control, mice were treated with 5-bromodeoxyuridine on Days 9 and 10. On Days 11 or 18, the fetuses were isolated. Compared with the sham-exposed group, the group exposed to EMP had increased rates of polydactyly fetuses (5.1% vs. 0.6%, P < 0.05) and abnormal gene expression (22.2% vs. 2.8%, P < 0.05). Ectopic expression of Fgf4 was detected in the apical ectodermal ridge, whereas overexpression and ectopic expression of Shh were detected in the zone of polarizing activity of limbs in the EMP-exposed group and in the positive control group. However, expression of Gli3 decreased in mesenchyme cells in those two groups. The percentages of programmed cell death of limbs in EMP-exposed and positive control group were decreased (3.57% and 2.94%, respectively, P < 0.05, compared with 7.76% in sham-exposed group). In conclusion, polydactyly induced by EMP was accompanied by abnormal expression of the above-mentioned genes and decreased percentage of programmed cell death during limb development. Copyright © 2013 Elsevier Inc. All rights reserved.

Lentiviral Infection of Rhesus Macaques Causes Long-Term Injury to Cortical and Hippocampal Projections of Prostaglandin-Expressing Cholinergic Basal Forebrain Neurons

PubMed Central

Depboylu, Candan; Weihe, Eberhard; Eiden, Lee E.

2011-01-01

The simian immunodeficiency virus (SIV) macaque model resembles human HIV-AIDS and associated brain dysfunction. Altered expression of synaptic markers and transmitters in neuro-AIDS has been reported, but limited data exist for the cholinergic system and lipid mediators such as prostaglandins. Here, we analyzed cholinergic basal forebrain neurons with their telencephalic projections and the rate-limiting enzymes for prostaglandin synthesis, cyclooxygenases 1 and 2 (COX1 and 2) in brains of SIV-infected macaques with and without encephalitis and antiretroviral therapy, and uninfected controls. COX1 but not COX2 was co-expressed with markers of cholinergic phenotype, i.e. choline acetyltransferase and vesicular acetylcholine transporter (VAChT), in basal forebrain neurons of monkey, as well as human samples. COX1 was decreased in basal forebrain neurons in macaques with AIDS vs. uninfected and asymptomatic SIV-infected macaques. VAChT-positive fiber density was reduced in frontal, parietal and hippocampal-entorhinal cortex. Although brain SIV burden and associated COX1- and COX2-positive mononuclear and endothelial inflammatory reactions were mostly reversed in AIDS-diseased macaques that received 6-chloro-2′,3′-dideoxyguanosine treatment, decreased VAChT-positive terminal density and reduced cholinergic COX1 expression were not. Thus, COX1 expression is a feature of primate cholinergic basal forebrain neurons; it may be functionally important and a critical biomarker of cholinergic dysregulation accompanying lentiviral encephalopathy. These results imply that insufficiently prompt initiation of antiretroviral therapy in lentiviral infection may lead to neurostructurally unremarkable but neurochemically prominent, irreversible brain damage. PMID:22157616

Apoptosis and cell proliferation in the development of gastric carcinomas: associations with c-myc and p53 protein expression.

PubMed

Ishii, Hideaki H; Gobé, Glenda C; Pan, Wenshen; Yoneyama, Juichi; Ebihara, Yoshiro

2002-09-01

Patients with gastric carcinomas have a poor prognosis and low survival rates. The aim of the present paper was to characterize cellular and molecular properties to provide insight into aspects of tumor progression in early compared with advanced gastric cancers. One hundred and nine graded gastric carcinomas (early or advanced stage, undifferentiated or differentiated type) with paired non-cancer tissue were studied to define the correlation between apoptosis (morphology, terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling), cell proliferation (Ki-67 expression, morphology) and expression and localization of two proteins frequently having altered expression in cancers, namely p53 and c-myc. Overall, apoptosis was lower in early stage, differentiated and undifferentiated gastric carcinomas compared with advanced-stage cancers. Cell proliferation was comparatively high in all stages. There was a high level of p53 positivity in all stages. Only the early- and advanced-stage undifferentiated cancers that were p53 positive had a significantly higher level of apoptosis (P < 0.05). Cell proliferation was significantly greater (P < 0.05) only in the early undifferentiated cancers that had either c-myc or p53-positivity. The results indicate that low apoptosis and high cell proliferation combine to drive gastric cancer development. The molecular controls for high cell proliferation of the early stage undifferentiated gastric cancers involve overexpression of both p53 and c-myc. Overexpression of p53 may also control cancer development in that its expression is associated with higher levels of apoptosis in early and late-stage undifferentiated, cancers. Copyright 2002 Blackwell Publishing Asia Pty Ltd

Expression of Bmi-1, P16, and CD44v6 in Uterine Cervical Carcinoma and Its Clinical Significance

PubMed Central

Weng, Mei-ying; Li, Lin; Feng, Shu-ying; Hong, Shun-jia

2012-01-01

Objective Bmi-1, a putative proto-oncogene, is a core member of the polycomb gene family, which is expressed in many human tumors. The p16 protein negatively regulated cell proliferation, whereas CD44v6 is associated with proliferation as an important protein. Additionally, CD44v6 is an important nuclear antigen closely correlated to tumor metastasis. The present study aims to investigate the expression and significance of Bmi-1, p16, and CD44v6 in uterine cervical carcinoma (UCC). Methods A total of 62 UCC, 30 cervical neoplasic, and 20 normal cervical mucosal tissues were used in the current study. The expression of Bmi-1, p16, and CD44v6 in these tissues was determined using immunohistochemical assay. The relationships among the expression of these indices, the clinicopathologic features of UCC, and the survival rate of UCC patients were also discussed. The correlation between Bmi-1 protein expression and p16 or CD44v6 protein in UCC was analyzed. Results The expression of Bmi-1, p16, and CD44v6 was significantly high in cervical carcinoma compared with that in the cervical neoplasia and normal colorectal mucosa (P<0.05). The over-expression of Bmi-1 protein in UCC was apparently related to the distant metastasis (P<0.01) and the tumor, nodes and metastasis-classification, i.e. the TNM staging, World Health Organization (P<0.05). Nevertheless, the positive expression of p16 protein in UCC was not significantly associated with the clinicopathologic features (P>0.05). The Kaplan–Meier survival analysis showed that the over-expression of Bmi-1 significantly decreased the survival rate of UCC patients (P<0.05). A strong correlation indicated that there was statistical significance between the expression of Bmi-1 and CD44V6 proteins in UCC (r=0.419, P=0.001). Conclusions The over-expression of Bmi-1 and CD44v6 protein closely correlate to the tumorigenesis, metastasis, and prognosis of UCC. Bmi-1 and CD44v6 may be used to predict the prognosis of cervical carcinoma. Bmi-1 may indirectly regulate the expression of CD44v6 in UCC patients. The positive expression of p16 protein is possibly associated with the tumorigenesis, but not with the metastasis or prognosis of UCC. PMID:23691455

Ribosome flow model with positive feedback

PubMed Central

Margaliot, Michael; Tuller, Tamir

2013-01-01

Eukaryotic mRNAs usually form a circular structure; thus, ribosomes that terminatae translation at the 3′ end can diffuse with increased probability to the 5′ end of the transcript, initiating another cycle of translation. This phenomenon describes ribosomal flow with positive feedback—an increase in the flow of ribosomes terminating translating the open reading frame increases the ribosomal initiation rate. The aim of this paper is to model and rigorously analyse translation with feedback. We suggest a modified version of the ribosome flow model, called the ribosome flow model with input and output. In this model, the input is the initiation rate and the output is the translation rate. We analyse this model after closing the loop with a positive linear feedback. We show that the closed-loop system admits a unique globally asymptotically stable equilibrium point. From a biophysical point of view, this means that there exists a unique steady state of ribosome distributions along the mRNA, and thus a unique steady-state translation rate. The solution from any initial distribution will converge to this steady state. The steady-state distribution demonstrates a decrease in ribosome density along the coding sequence. For the case of constant elongation rates, we obtain expressions relating the model parameters to the equilibrium point. These results may perhaps be used to re-engineer the biological system in order to obtain a desired translation rate. PMID:23720534

CD44 expression is related to poor prognosis of hypopharyngeal squamous cell carcinoma.

PubMed

Uwa, Nobuhiro; Kataoka, Tatsuki R; Torii, Ikuko; Sato, Ayuko; Nishigami, Takashi; Song, Misa; Daimon, Takashi; Saeki, Nobuo; Sagawa, Kousuke; Mouri, Takeshi; Terada, Tomonori; Sakagami, Masafumi; Tsujimura, Tohru

2011-03-01

CD44 expression in hypopharyngeal squamous cell carcinomas (SCCs) is closely associated with poor prognosis for patients. CD44 may serve as a prognostic marker for hypopharyngeal SCCs. CD44, an adhesion molecule binding to extracellular matrix, is believed to participate in the progression of malignancies. To clarify the role of CD44 in the progression of hypopharyngeal SCCs, we examined CD44 expression in relation to clinical parameters in hypopharyngeal SCCs. Biopsy specimens of hypopharyngeal SCCs were collected from 40 untreated patients, and their CD44 expression was examined immunohistochemically. Hypopharyngeal SCCs were classified into two groups: CD44-low SCCs comprising < 50% CD44-positive tumor cells and CD44-high SCCs comprising ≥ 50% CD44-positive tumor cells. The relation between CD44 expression and various parameters (clinical T and N stages, distant metastasis, and pathological T and N stages) was analyzed by Fisher's exact test. The relation between CD44 expression and the 5-year disease-free survival (DFS) rate was also analyzed by log rank test. The CD44 expression in hypopharyngeal SCCs was related to pathological N stage, but not to clinical T and N stages and pathological T stage, of the patients. Distant metastasis during the follow-up occurred more frequently in patients with CD44-high SCCs than those with CD44-low SCCs. The 5-year DFS was significantly lower in the former than in the latter.

Aquaporin 1 expression is associated with response to adjuvant chemotherapy in stage II and III colorectal cancer.

PubMed

Imaizumi, Hideko; Ishibashi, Keiichiro; Takenoshita, Seiichi; Ishida, Hideyuki

2018-05-01

Aquaporin 1 (AQP1), which functions as a water transporter, is associated with cancer cell proliferation, invasion, metastasis and angiogenesis in numerous types of solid cancer, including colorectal cancer (CRC). The focus of the present study was to address the potential clinical use of AQP1 expression in CRC as a prognostic and predictive biomarker for disease recurrence and therapeutic outcomes. The current study investigated the expression of AQP1 in surgically resected specimens from 268 patients with stage 0-IV CRC. AQP1 expression was positive in 112 (41.8%) patients, and was significantly associated with left-sided tumors (P<0.01) and with aggressive tumor phenotypes, including depth of invasion (P=0.03), lymph node metastasis (P=0.03), lymphatic invasion (P<0.01) and venous invasion (P<0.01). However, AQP1 expression had no significant prognostic effect on disease-free survival (DFS) in patients with stage II and III CRC following curative surgery. In 84 stage II and III patients who were administered 5-fluorouracil-based adjuvant chemotherapy, positive AQP1 expression was associated with an increased DFS rate compared with that of AQP1-negative patients (P=0.05). Additionally, these results identified that receiving adjuvant chemotherapy was not beneficial to patients with AQP1-negative tumors. This suggests that the expression of AQP1 may be a candidate biomarker predictive of response to 5-fluorouracil-based adjuvant chemotherapy following surgery in patients with stage II and III CRC.

Characterization of Gastric and Neuronal Histaminergic Populations Using a Transgenic Mouse Model

PubMed Central

Walker, Angela K.; Park, Won-Mee; Chuang, Jen-Chieh; Perello, Mario; Sakata, Ichiro; Osborne-Lawrence, Sherri; Zigman, Jeffrey M.

2013-01-01

Histamine is a potent biogenic amine that mediates numerous physiological processes throughout the body, including digestion, sleep, and immunity. It is synthesized by gastric enterochromaffin-like cells, a specific set of hypothalamic neurons, as well as a subset of white blood cells, including mast cells. Much remains to be learned about these varied histamine-producing cell populations. Here, we report the validation of a transgenic mouse line in which Cre recombinase expression has been targeted to cells expressing histidine decarboxylase (HDC), which catalyzes the rate-limiting step in the synthesis of histamine. This was achieved by crossing the HDC-Cre mouse line with Rosa26-tdTomato reporter mice, thus resulting in the expression of the fluorescent Tomato (Tmt) signal in cells containing Cre recombinase activity. As expected, the Tmt signal co-localized with HDC-immunoreactivity within the gastric mucosa and gastric submucosa and also within the tuberomamillary nucleus of the brain. HDC expression within Tmt-positive gastric cells was further confirmed by quantitative PCR analysis of mRNA isolated from highly purified populations of Tmt-positive cells obtained by fluorescent activated cell sorting (FACS). HDC expression within these FACS-separated cells was found to coincide with other markers of both ECL cells and mast cells. Gastrin expression was co-localized with HDC expression in a subset of histaminergic gastric mucosal cells. We suggest that these transgenic mice will facilitate future studies aimed at investigating the function of histamine-producing cells. PMID:23555941

"So Happy I Could Shout!" and "So Happy I Could Cry!" Dimorphous expressions represent and communicate motivational aspects of positive emotions.

PubMed

Aragón, Oriana R; Bargh, John A

2018-03-01

Happiness can be expressed through smiles. Happiness can also be expressed through physical displays that without context, would appear to be sadness (tears, downward turned mouths, and crumpled body postures) and anger (clenched jaws, snarled lips, furrowed brows, and pumped fists). These seemingly incongruent displays of happiness, termed dimorphous expressions, we propose, represent and communicate expressers' motivational orientations. When participants reported their own aggressive expressions in positive or negative contexts, their expressions represented positive or negative emotional experiences respectively, imbued with appetitive orientations (feelings of wanting to go). In contrast, reported sad expressions, in positive or negative contexts, represented positive and negative emotional experiences respectively, imbued with consummatory orientations (feelings of wanting to pause). In six additional experiments, participant observers interpreted that aggression displayed in positive contexts signalled happy-appetitive states, and sadness displayed in positive contexts signalled happy-consummatory states. Implications for the production and interpretation of emotion expressions are discussed.

Decline in the Quality of Family Relationships Predicts Escalation in Children’s Internalizing Symptoms from Middle to Late Childhood

PubMed Central

Kochanska, Grazyna

2015-01-01

An integration of family systems perspectives with developmental psychopathology provides a framework for examining the complex interplay between family processes and developmental trajectories of child psychopathology over time. In a community sample of 98 families, we investigated the evolution of family relationships, across multiple subsystems of the family (i.e., interparental, mother-child, father-child), and the impact of these changing family dynamics on developmental trajectories of child internalizing symptoms over 6 years, from preschool age to pre-adolescence. Parent–child relationship quality was observed during lengthy sessions, consisting of multiple naturalistic, carefully scripted contexts. Each parent completed reports about interparental relationship satisfaction and child internalizing symptoms. To the extent that mothers experienced a steeper decline in interparental relationship satisfaction over time, children developed internalizing symptoms at a faster rate. Further, symptoms escalated at a faster rate to the extent that negative mother-child relationship quality increased (more negative affect expressed by both mother and child, greater maternal power assertion) and positive mother-child relationship quality decreased (less positive affect expressed by both mother and child, less warmth and positive reciprocity). Time-lagged growth curve analyses established temporal precedence such that decline in family relationships preceded escalation in child internalizing symptoms. Results suggest that family dysfunction, across multiple subsystems, represents a driving force in the progression of child internalizing symptoms. PMID:25790794

Decline in the Quality of Family Relationships Predicts Escalation in Children's Internalizing Symptoms from Middle to Late Childhood.

PubMed

Brock, Rebecca L; Kochanska, Grazyna

2015-10-01

An integration of family systems perspectives with developmental psychopathology provides a framework for examining the complex interplay between family processes and developmental trajectories of child psychopathology over time. In a community sample of 98 families, we investigated the evolution of family relationships, across multiple subsystems of the family (i.e., interparental, mother-child, father-child), and the impact of these changing family dynamics on developmental trajectories of child internalizing symptoms over 6 years, from preschool age to pre-adolescence. Parent-child relationship quality was observed during lengthy sessions, consisting of multiple naturalistic, carefully scripted contexts. Each parent completed reports about interparental relationship satisfaction and child internalizing symptoms. To the extent that mothers experienced a steeper decline in interparental relationship satisfaction over time, children developed internalizing symptoms at a faster rate. Further, symptoms escalated at a faster rate to the extent that negative mother-child relationship quality increased (more negative affect expressed by both mother and child, greater maternal power assertion) and positive mother-child relationship quality decreased (less positive affect expressed by both mother and child, less warmth and positive reciprocity). Time-lagged growth curve analyses established temporal precedence such that decline in family relationships preceded escalation in child internalizing symptoms. Results suggest that family dysfunction, across multiple subsystems, represents a driving force in the progression of child internalizing symptoms.

Extreme Metal Music and Anger Processing

PubMed Central

Sharman, Leah; Dingle, Genevieve A.

2015-01-01

The claim that listening to extreme music causes anger, and expressions of anger such as aggression and delinquency have yet to be substantiated using controlled experimental methods. In this study, 39 extreme music listeners aged 18–34 years were subjected to an anger induction, followed by random assignment to 10 min of listening to extreme music from their own playlist, or 10 min silence (control). Measures of emotion included heart rate and subjective ratings on the Positive and Negative Affect Scale (PANAS). Results showed that ratings of PANAS hostility, irritability, and stress increased during the anger induction, and decreased after the music or silence. Heart rate increased during the anger induction and was sustained (not increased) in the music condition, and decreased in the silence condition. PANAS active and inspired ratings increased during music listening, an effect that was not seen in controls. The findings indicate that extreme music did not make angry participants angrier; rather, it appeared to match their physiological arousal and result in an increase in positive emotions. Listening to extreme music may represent a healthy way of processing anger for these listeners. PMID:26052277

A statistical model of false negative and false positive detection of phase singularities.

PubMed

Jacquemet, Vincent

2017-10-01

The complexity of cardiac fibrillation dynamics can be assessed by analyzing the distribution of phase singularities (PSs) observed using mapping systems. Interelectrode distance, however, limits the accuracy of PS detection. To investigate in a theoretical framework the PS false negative and false positive rates in relation to the characteristics of the mapping system and fibrillation dynamics, we propose a statistical model of phase maps with controllable number and locations of PSs. In this model, phase maps are generated from randomly distributed PSs with physiologically-plausible directions of rotation. Noise and distortion of the phase are added. PSs are detected using topological charge contour integrals on regular grids of varying resolutions. Over 100 × 10 6 realizations of the random field process are used to estimate average false negative and false positive rates using a Monte-Carlo approach. The false detection rates are shown to depend on the average distance between neighboring PSs expressed in units of interelectrode distance, following approximately a power law with exponents in the range of 1.14 to 2 for false negatives and around 2.8 for false positives. In the presence of noise or distortion of phase, false detection rates at high resolution tend to a non-zero noise-dependent lower bound. This model provides an easy-to-implement tool for benchmarking PS detection algorithms over a broad range of configurations with multiple PSs.

How does the emotive content of televised anti-smoking mass media campaigns influence monthly calls to the NHS Stop Smoking helpline in England?

PubMed

Richardson, Sol; Langley, Tessa; Szatkowski, Lisa; Sims, Michelle; Gilmore, Anna; McNeill, Ann; Lewis, Sarah

2014-12-01

To investigate the effects of different types of televised mass media campaign content on calls to the English NHS Stop Smoking helpline. We used UK government-funded televised tobacco control campaigns from April 2005 to April 2010, categorised as either "positive" (eliciting happiness, satisfaction or hope) or "negative" (eliciting fear, guilt or disgust). We built negative binomial generalised additive models (GAMs) with linear and smooth terms for monthly per capita exposure to each campaign type (expressed as Gross Ratings Points, or GRPs) to determine their effect on calls in the same month. We adjusted for seasonal trends, inflation-adjusted weighted average cigarette prices and other tobacco control policies. We found non-linear associations between exposure to positive and negative emotive campaigns and quitline calls. The rate of calls increased more than 50% as exposure to positive campaigns increased from 0 to 400 GRPs (rate ratio: 1.58, 95% CI: 1.25-2.01). An increase in calls in response to negative emotive campaigns was only apparent after monthly exposure exceeded 400 GRPs. While positive campaigns were most effective at increasing quitline calls, those with negative emotive content were also found to impact on call rates but only at higher levels of exposure. Copyright © 2014. Published by Elsevier Inc.

[MRI findings and pathological features of occult breast cancer].

PubMed

Zhang, J J; Yang, X T; Du, X S; Zhang, J X; Hou, L N; Niu, J L

2018-01-23

Objective: To investigate the magnetic resonance imaging (MRI) findings and clinicopathological features of primary lesions in patients with occult breast cancer (OBC). Methods: The imaging reports from the Breast Imaging Reporting and Data System in 2013 were retrospectively analyzed to investigate the morphology and the time signal intensity curve (TIC) of breast lesions in patients with OBC. The clinical and pathological characteristics of these patients were also included. Results: A total of 34 patients were enrolled. Among these patients, 24 patients underwent modified radical mastectomy and 18 of them had primary breast carcinoma in pathological sections. MRI detected 17 cases of primary lesions, including six masse lesions with a diameter of 0.6-1.2 cm (average 0.9 cm), and 11 non-mass lesions with four linear distributions, three segmental distributions, three focal distributions, and one regions distribution. Five patients had TIC typeⅠprimary lesions, ten had TIC type Ⅱ primary lesions, and two had TIC type Ⅲ primary lesions. Among all 34 cases, 23 of them had complete results of immunohistochemistry: 11 estrogen receptor (ER) positive lesions (47.8%), tenprogesterone receptor (PR) positive lesions (43.5%), seven human epidermal growth factor receptor 2 (HER-2) positive lesions (30.4%), and 20high expression(>14%) of Ki-67 (87.0%). The proportion of type luminal A was 4.3%, type luminal B was 43.5%, triple negative breast cancer (TNBC) was 30.4%, and HER-2 over expression accounted for 21.7%. Conclusions: The primary lesions of OBC usually manifested as small mass lesions, or focal, linear or segmental distribution of non-mass lesions. The positive rate of ER and PR was low, but the positive rate of HER-2 and the proliferation index of Ki-67 was high. Type luminal B is the most common molecular subtype.

[Expression of EphA2 in Metastatic and Non-Metastatic Primary Uveal Melanoma].

PubMed

Vukoja, V; Brandenbusch, T; Tura, A; Nassar, K; Rohrbach, D J M; Lüke, M; Grisanti, S; Lüke, J

2016-03-01

Little is known about how the expression of Ephrin type-A receptor 2 (EphA2) influences cell-cell adhesion, migration, angiogenesis, and the formation of vasculogenic mimicry (VM) channels in uveal melanomas or how this may be related to the rate of metastasis. Paraffin embedded sections of 50 histopathologically well characterised primary uveal melanomas (mean largest tumour diameter: 16.3 mm) were evaluated with respect to the expression of EphA2. Systemic metastasis was detected in 29 patients. The remaining 21 patients were followed for a mean of 10 years. Tumour angiogensis was analysed by endoglin expression (CD105), the activity of the mature vascular system (von Willebrand factor) and the presence of VM (CD31/PAS staining). All uveal melanomas expressed EphA2, with a mean of 95.93 % positive cells ± SD: 6.3 %. There was no significant association between EphA2 and the rate of metastases (p = 0.196), endoglin expression (p = 0.652), VM (p = 0.267) or with any other clinical or histopathological factors (p < 0.05). However, there was significant up-regulation of EphA2 in the nucleus of the metastatic uveal melanoma subgroup, while cytoplasmatic localisation in the subgroup was associated with better prognosis (p = 0.006). There were low levels of EphA2 expression in the specific retinal layers, the ciliary and corneal epithelium, and the choroidal and corneal endothelium. Nuclear expression of EphA2 in this series of large tumours was significantly associated with an increased rate of metastasis. On the other hand, cytoplasmic localisation was associated with a better prognosis. As there was no correlation between EphA2 expression and angiogenesis, the mature vasculature or VM, EphA2 appears to become less important in the advanced stages of the disease. Georg Thieme Verlag KG Stuttgart · New York.

Laying traits and underlying transcripts, expressed in the hypothalamus and pituitary gland, that were associated with egg production variability in chickens.

PubMed

Chen, Chih-Feng; Shiue, Yow-Ling; Yen, Cheng-Ju; Tang, Pin-Chi; Chang, Hui-Chiu; Lee, Yen-Pai

2007-12-01

The objective was to characterize the potential laying traits and underlying transcripts expressed in the hypothalamus and pituitary gland that were associated with egg production variability in five genetic stocks of chickens: two commercial lines, Red- (n=12) and Black-feather (n=14) Taiwan country chickens (TCCs); two selected lines of TCCs, B (high body weight/comb size; n=17) and L2 (high-egg production; n=14); and a commercial single comb White Leghorn (WL; n=17). Six laying traits, age at first egg, clutch length, pause length, oviposition lag within clutch, follicle rapid growth period, and rate of yolk accumulation were measured. The significance of differential values among five chicken stocks and correlation coefficients between laying traits and number of eggs to 50 weeks of age or laying rate after first egg, and the expression level of 33 transcripts were determined. Longer clutch length and shorter oviposition lag within clutch contributed to a higher number of eggs to 50 weeks of age or laying rate after first egg in L2 (P<0.05) and WL strains (P<0.05). However, their rate of yolk accumulation (P<0.05) and follicle rapid growth period (P<0.05) were different, indicating the accumulation of different alleles after long-term, independent selection. Across all five strains, numbers of eggs to 50 weeks of age were positive correlated with average clutch length (P<0.05) as well as the rate of yolk accumulation (P<0.05). Expressions of PLAG1, STMN2, PGDS, PARK7, ANP32A, PCDHA@, SCG2, BDH and SAR1A transcripts contributed to number of eggs to 50 weeks of age (P<0.05) or laying rate after first egg (P<0.05). Analysis of correlation coefficients indicated that PLAG1 additionally played roles in decreasing average pause length. Two transcripts, PRL and GARNL1, specifically contributed to number of eggs to 50 weeks of age or laying rate after first egg by reducing oviposition lag within clutch (P<0.05) and/or increasing average clutch length (P<0.05), respectively. Expression level of NCAM1, contributed to laying rate after first egg by association with a shorter oviposition lag within clutch (P<0.05). The current study attributed egg production phenotype in five strains into several laying traits; correlations between these traits and expression levels of underlying transcripts expressed in the hypothalamus and pituitary gland were also established.

p14 expression differences in ovarian benign, borderline and malignant epithelial tumors.

PubMed

Cabral, Vinicius Duarte; Cerski, Marcelle Reesink; Sa Brito, Ivana Trindade; Kliemann, Lucia Maria

2016-10-22

Abnormalities in tumor suppressors p14, p16 and p53 are reported in several human cancers. In ovarian epithelial carcinogenesis, p16 and p53 show higher immunohistochemical staining frequencies in malignant tumors and are associated with poor prognoses. p14 was only analyzed in carcinomas, with conflicting results. There are no reports on its expression in benign and borderline tumors. This study aims to determine p14, p16 and p53 expression frequencies in ovarian benign, borderline and malignant tumors and their associations with clinical parameters. A cross-sectional study utilizing immunohistochemistry was performed on paraffin-embedded ovarian epithelial tumor samples. Clinical data were collected from medical records. Fisher's exact test and the Bonferroni correction were performed for frequency associations. Survival comparisons utilized Kaplan-Meier and log rank testing. Associations were considered significant when p < 0.05. p14 absent expression was associated with malignant tumors (60 % positive) (p = 0.000), while 93 % and 94 % of benign and borderline tumors, respectively, were positive. p16 was positive in 94.6 % of carcinomas, 75 % of borderline and 45.7 % of benign tumors (p = 0.000). p53 negative staining was associated with benign tumors (2.9 % positive) (p = 0.016) but no difference was observed between borderline (16.7 %) and malignant tumors (29.7 %) (p = 0.560). No associations were found between expression rates, disease-free survival times or clinical variables. Carcinoma subtypes showed no difference in expression. This is the first description of p14 expression in benign and borderline tumors. It remains stable in benign and borderline tumors, while carcinomas show a significant absence of staining. This may indicate that p14 abnormalities occur later in carcinogenesis. p16 and p53 frequencies increase from benign to borderline and malignant tumors, similarly to previous reports, possibly reflecting the accumulation of inactive mutant protein. The small sample size may have prevented statistically significant survival analyses and clinical correlations. Future studies should investigate genetic abnormalities in p14 coding sequences and include all types of ovarian epithelial tumors. Bigger sample sizes may be needed for significant associations.

IMP3 expression is associated with poor outcome and epigenetic deregulation in intrahepatic cholangiocarcinoma.

PubMed

Gao, Yuanyuan; Yang, Michelle; Jiang, Zhong; Woda, Bruce A; Mercurio, Arthur M; Qin, Jianjie; Huang, Xinli; Zhang, Feng

2014-06-01

IMP3 is a fetal protein not expressed in normal adult tissues. IMP3 is an oncoprotein and a useful biomarker for a variety of malignancies and is associated with reduced overall survival of a number of them. IMP3 expression and its prognostic value for patients with intrahepatic cholangiocarcinoma (ICC) have not been well investigated. The molecular mechanism underlying IMP3 expression in human cancer cells remains to be elucidated. Here we investigated IMP3 expression in ICC and adjacent nonneoplastic liver in 72 unifocal primary ICCs from a single institute by immunohistochemistry, immunoblotting, and real-time polymerase chain reaction. IMP3 was specifically expressed in cancer cells but not in the surrounding normal tissue, and 59 (82%) of 72 ICCs were IMP3 positive by immunohistochemistry. Among 35 cases with lymphovascular invasion, 26 (74%) showed IMP3 positivity in lymph node metastases. IMP3 expression was significantly correlated with tumor size, pathological grade, metastasis, and clinical stage. Kaplan-Meier analysis demonstrated an inverse correlation between IMP3 expression and overall survival rate. Multivariate analysis revealed that IMP3 was the only risk factor associated with survival. To further explore the mechanism of IMP3 expression in cancers, we identified 2 CpG islands at IMP3 proximal promoter. Interestingly, the IMP3 promoter was almost completely demethylated in ICCs in contrast to densely methylated promoter in normal liver tissues. IMP3 expression is a useful biomarker for ICCs and can provide an independent prognostic value for patients with ICC. To our knoweldge, this is the first direct evidence of epigenetic deregulation of IMP3 in human cancer. Copyright © 2014 The Auhtors. Published by Elsevier Inc. All rights reserved.

Perceptions of affectionate communication among people with unfavorable and favorable attitudes toward homosexuality.

PubMed

Brantley-Hill, Stacia M; Brinthaupt, Thomas M

2014-01-01

People are sometimes hesitant to communicate affection if it might be misinterpreted by the intended receiver or an audience. We hypothesized that anti-gay/-lesbian attitudes might negatively affect the perceived appropriateness of expressing affection. One hundred and twenty male and female undergraduates with either very high or very low levels of anti-gay/-lesbian attitudes participated in the study. They rated the appropriateness of expressing affection toward same- and other-sex targets in a set of 2 (public or private setting) × 3 (positive, neutral, or negative valence) scenarios. Results supported a "generalized inhibition" effect, with high levels of anti-gay/-lesbian attitudes associated with a reluctance to express affection regardless of target, setting, valence, or current relationship status. Implications for research on affectionate expression and anti-gay/-lesbian attitudes are presented.

Validation of nuclear STAT6 immunostaining as a diagnostic marker of meningeal solitary fibrous tumor (SFT)/hemangiopericytoma.

PubMed

Berghoff, Anna S; Kresl, Philip; Bienkowski, Michal; Koelsche, Christian; Rajky, Ursula; Hainfellner, Johannes A; Preusser, Matthias

NAB2-STAT6 gene fusion is a molecular characteristic of solitary fibrous tumors (SFT) and hemangiopericytoma, underscoring their definition as one diagnostic entity. NAB2-STAT6 fusion is associated with nuclear relocation of STAT6 protein that can be detected by immunohistochemistry. We evaluated the diagnostic value of STAT6 expression in meningeal tumors. 77 meningeal tumors (17/77 (22.0%) SFT/hemangiopericytoma, 11/77 meningothelial meningioma, 10/77 atypical meningioma 8/77 chordoid meningioma, 9/77 fibroblastic meningioma, 10/77 transitional meningioma, 3/77 rhabdoid meningioma and 9/77 anaplastic meningioma) were included. STAT6 immunohistochemistry was performed on FFPE specimens using a fully automated slide-staining system and anti-STAT6 antibody SC-20:sc621. Two independent observers analyzed all specimens blinded to histological diagnoses, and a third observer was consulted in case of discordancy. STAT6 immunohistochemistry yielded an exclusively nuclear immunostaining signal. 16/17 (94%) SFT/hemangiopericytoma specimens presented with clear-cut, wide-spread, and moderate to strong staining in tumor cell nuclei and were rated as STAT6-positive. In only 1 SFT case with weak and focal nuclear STAT6 immunostaining signal, STAT6 expression was rated discordant (observer 1: STAT6-negative, observers 2 and 3: STAT6-positive). All non-SFT/hemangiopericytoma cases were unanimously rated as STAT6-negative. In 76/77 (98.7%) cases the evaluation of STAT6 immunostaining results was in agreement among observers. STAT6 immunohistochemistry is a robust method to verify diagnosis of SFT/hemangiopericytoma and should therefore be included in the diagnostic work-up of meningeal tumors. In singular cases, weak and focal STAT6 expression may lead to false-negative evaluation and may prompt further molecular work-up.
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Facial expressions and pair bonds in hylobatids.

PubMed

Florkiewicz, Brittany; Skollar, Gabriella; Reichard, Ulrich H

2018-06-06

Facial expressions are an important component of primate communication that functions to transmit social information and modulate intentions and motivations. Chimpanzees and macaques, for example, produce a variety of facial expressions when communicating with conspecifics. Hylobatids also produce various facial expressions; however, the origin and function of these facial expressions are still largely unclear. It has been suggested that larger facial expression repertoires may have evolved in the context of social complexity, but this link has yet to be tested at a broader empirical basis. The social complexity hypothesis offers a possible explanation for the evolution of complex communicative signals such as facial expressions, because as the complexity of an individual's social environment increases so does the need for communicative signals. We used an intraspecies, pair-focused study design to test the link between facial expressions and sociality within hylobatids, specifically the strength of pair-bonds. The current study compared 206 hr of video and 103 hr of focal animal data for ten hylobatid pairs from three genera (Nomascus, Hoolock, and Hylobates) living at the Gibbon Conservation Center. Using video footage, we explored 5,969 facial expressions along three dimensions: repertoire use, repertoire breadth, and facial expression synchrony [FES]. We then used focal animal data to compare dimensions of facial expressiveness to pair bond strength and behavioral synchrony. Hylobatids in our study overlapped in only half of their facial expressions (50%) with the only other detailed, quantitative study of hylobatid facial expressions, while 27 facial expressions were uniquely observed in our study animals. Taken together, hylobatids have a large facial expression repertoire of at least 80 unique facial expressions. Contrary to our prediction, facial repertoire composition was not significantly correlated with pair bond strength, rates of territorial synchrony, or rates of behavioral synchrony. We found that FES was the strongest measure of hylobatid expressiveness and was significantly positively correlated with higher sociality index scores; however, FES showed no significant correlation with behavioral synchrony. No noticeable differences between pairs were found regarding rates of behavioral or territorial synchrony. Facial repertoire sizes and FES were not significantly correlated with rates of behavioral synchrony or territorial synchrony. Our study confirms an important role of facial expressions in maintaining pair bonds and coordinating activities in hylobatids. Data support the hypothesis that facial expressions and sociality have been linked in hylobatid and primate evolution. It is possible that larger facial repertoires may have contributed to strengthening pair bonds in primates, because richer facial repertoires provide more opportunities for FES which can effectively increase the "understanding" between partners through smoother coordination of interaction patterns. This study supports the social complexity hypothesis as the driving force for the evolution of complex communication signaling. © 2018 Wiley Periodicals, Inc.

Overexpression of c-kit(CD117), relevant with microvessel density, is an independent survival prognostic factor for patients with HBV-related hepatocellular carcinoma.

PubMed

Yan, Weiwei; Zhu, Zhenyu; Pan, Fei; Huang, Ang; Dai, Guang-Hai

2018-01-01

To explore new biomarkers for indicating the recurrence and prognosis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients after tumor resection, we investigated the expression and prognostic value of c-kit(CD117) in HBV-related HCC. Immunohistochemistry was used to estimate the expression of c-kit(CD117) and CD34 in the liver cancer tissues. The correlations between the expression of these biomarkers and the clinicopathologic characteristics were analyzed. The positive rate of c-kit(CD117) expression in 206 HCC cases was 48.1%, and c-kit expression was significantly related with CD34-positive microvessel density. CD34-microvessel density numbers were much higher in c-kit(+) HCC tissues than in c-kit(-) HCC tissues (44.13±17.01 vs 26.87±13.16, P =0.003). The expression of c-kit was significantly higher in patients with Edmondson grade III-IV ( P <0.001) and TNM stage III ( P <0.001). Moreover, Kaplan-Meier survival analysis showed that c-kit ( P <0.001) expression was correlated with reduced disease-free survival (DFS). Multivariate analysis identified c-kit as an independent poor prognostic factor of DFS in HCC patients ( P <0.001). Increased c-kit expression could be considered as an independent unfavorable prognostic factor for predicting DFS in HBV-related HCC patients after surgery. These results could be used to identify patients at a higher risk of early tumor recurrence and poor prognosis.

CLONING AND EXPRESSION OF THE TRANSLOCATOR PROTEIN (18 KDA), VOLTAGE-DEPENDENT ANION CHANNEL, AND DIAZEPAM BINDING INHIBITOR IN THE GONAD OF LARGEMOUTH BASS (MICROPTERUS SALMOIDES) ACROSS THE REPRODUCTIVE CYCLE

PubMed Central

Doperalski, Nicholas J.; Martyniuk, Christopher J.; Prucha, Melinda S.; Kroll, Kevin J.; Denslow, Nancy D.; Barber, David S.

2011-01-01

Cholesterol transport across the mitochondrial membrane is rate-limiting for steroidogenesis in vertebrates. Previous studies in fish have characterized expression of the steroidogenic acute regulatory protein, however the function and regulation of other genes and proteins involved in piscine cholesterol transport have not been evaluated. In the current study, mRNA sequences of the 18 kDa translocator protein (tspo; formerly peripheral benzodiazepine receptor), voltage-dependent anion channel (vdac), and diazepam binding inhibitor (dbi; also acyl-CoA binding protein) were cloned from largemouth bass. Gonadal expression was examined across reproductive stages to determine if expression is correlated with changes in steroid levels and with indicators of reproductive maturation. In testis, transcript abundance of tspo and dbi increased with reproductive maturation (6- and 23-fold maximal increase, respectively) and expression of tspo and dbi was positively correlated with reproductive stage, gonadosomatic index (GSI), and circulating levels of testosterone. Testis vdac expression was positively correlated with reproductive stage and GSI. In females, gonadal tspo and vdac expression was negatively correlated with GSI and levels of plasma testosterone and 17β-estradiol. Ovarian dbi expression was not correlated with indicators of reproductive maturation. These studies represent the first investigation of the steroidogenic role of tspo, vdac, and dbi in fish. Findings suggest that cholesterol transport in largemouth bass testis, but not ovary, may be transcriptionally-regulated, however further investigation will be necessary to fully elucidate the role of these genes in largemouth bass steroidogenesis. PMID:21600210

Characterisation of the macrophage transcriptome in glomerulonephritis-susceptible and -resistant rat strains

PubMed Central

Maratou, Klio; Behmoaras, Jacques; Fewings, Chris; Srivastava, Prashant; D’Souza, Zelpha; Smith, Jennifer; Game, Laurence; Cook, Terence; Aitman, Tim

2010-01-01

Crescentic glomerulonephritis (CRGN) is a major cause of rapidly progressive renal failure for which the underlying genetic basis is unknown. WKY rats show marked susceptibility to CRGN, while Lewis rats are resistant. Glomerular injury and crescent formation are macrophage-dependent and mainly explained by seven quantitative trait loci (Crgn1-7). Here, we used microarray analysis in basal and lipopolysaccharide (LPS)-stimulated macrophages to identify genes that reside on pathways predisposing WKY rats to CRGN. We detected 97 novel positional candidates for the uncharacterised Crgn3-7. We identified 10 additional secondary effector genes with profound differences in expression between the two strains (>5-fold change, <1% False Discovery Rate) for basal and LPS-stimulated macrophages. Moreover, we identified 8 genes with differentially expressed alternatively spliced isoforms, by using an in depth analysis at probe-level that allowed us to discard false positives due to polymorphisms between the two rat strains. Pathway analysis identified several common linked pathways, enriched for differentially expressed genes, which affect macrophage activation. In summary, our results identify distinct macrophage transcriptome profiles between two rat strains that differ in susceptibility to glomerulonephritis, provide novel positional candidates for Crgn3-7, and define groups of genes that play a significant role in differential regulation of macrophage activity. PMID:21179115

Study of the diagnosis and treatment of cancer located in the head and neck and correlation with expression of prognostic markers.

PubMed

Bădulescu, Fl; Bădulescu, Adriana; Crişan, Anda; Popescu, Florina Carmen

2013-01-01

A prospective study made by authors was initiated in 2000 in order to analyze differences in terms of response rate, overall survival and progression free survival for patients with advanced head and neck carcinoma treated with radiotherapy vs. radiochemotherapy, respectively and to analyze the role of modern molecular biomarkers in the prognosis of these patients (p53, EGFR and Ki67). It was detected one significant difference appeared between the two groups for response rate (p<0.0001) and median overall survival [18.8 months in Group A and 17.2 months in Group B, with a hazard ratio for survival of 0.88 (95% CI, 0.75-1.12, p<0.0001]. Progression free survival was not significant different between these two groups [6.9 months for Group A and 7.2 months for Group B, p=0.3179]. Multivariate analysis by sex, age, TNM stage, site of disease, revealed TNM stage and site of disease as clinical phenotypes with predictive value. Also, the molecular biomarkers p53, EGFR and Ki67 have a prognostic significance in head and neck cancer in addition to the established clinical prognostic factors such as the stage, site of the tumor and the type of treatment. Because of material reasons, we decided to carry out the immunohistochemical marking in the group of patients who were radiochemotherapy-treated and the results of multivariate analysis reached statistical significance threshold in terms of response rate to treatment, overall survival and disease-free interval. Furthermore, immunohistochemical examination was not performed for patients with rhinopharyngeal carcinoma with marked radiochemosensibility and reduced tumor aggressiveness reflected in significantly better therapeutic outcomes by treatment response rate, overall survival and disease free interval. In the present study of the 93 cases that underwent immunohistochemical staining for EGFR, the majority (66 cases) showed a positive reaction for this marker, in 36 cases are highly immunohistochemical staining, and in 30 cases were weakly positive. In addition, cell proliferation was intense in 26 cases in which Ki67 index was greater than 45%, p53 protein expression was positive in 18 cases, but the majority (22) of cases showed a positive reaction for this marker; index was greater than 55%, and in the most (22) cases p53 protein was not expressed. Radio/chemoradiotherapy regimen associated with molecular anti-EGFR target therapy is standard therapy in advanced squamous head and neck carcinoma.

In vitro evaluation of a mammary gland specific expression vector encoding recombinant human lysozyme for development of transgenic dairy goat embryos.

PubMed

Gui, Tao; Zhang, Meiling; Chen, Jianwen; Zhang, Yuanliang; Zhou, Naru; Zhang, Yu; Tao, Jia; Sui, Liucai; Li, Yunsheng; Liu, Ya; Zhang, Xiaorong; Zhang, Yunhai

2012-08-01

A vector expressing human lysozyme (pBC1-hLYZ-GFP-Neo) was evaluated for gene and protein expression following liposome-mediated transformation of C-127 mouse mammary cancer cells. Cultures of G418-resistant clones were harvested 24-72 h after induction with prolactin, insulin and hydrocortisone. Target gene expression was analyzed by RT-PCR and Western blot and recombinant human lysozyme (rhLYZ) bacteriostatic activity was also evaluated. The hLYZ gene was correctly transcribed and translated in C-127 cells and hLYZ inhibited gram-positive bacterial growth, indicating the potential of this expression vector for development of a mammary gland bioreactor in goats. Guanzhong dairy goat skin fibroblasts transfected with pBC1-hLYZ-GFP-Neo were used to construct a goat embryo transgenically expressing rhLYZ by somatic nuclear transplantation with a blastocyst rate of 9.0 ± 2.8 %. These data establish the basis for cultivation of mastitis-resistant hLYZ transgenic goats.

Mucin expression profile of benign and malignant cervical tissues and correlation with clinical-pathologic parameters.

PubMed

Kong, X; Ding, L J; Wang, Z X

2017-01-01

To detect the expression of mucins in diverse benign and malignant cervical tissues of cervical disease. 158 cases of cervical tissues were collected. Sections were stained with monoclonal antibodies against MUC1, MUC2, MIUC4, MUC5AC, and MUC20 by immunohistochemistry. Normal cervical epithelium showed high expr ession of MUC1I, MUC4, and MUC5AC, partial expression of MUC20, and no MUC2. With the development from chronic cervicitis, cervical intraepithelial neoplasia (CI7N) to cervical squamous cell carcinoma (SCC), the expression of MUC1, NMUC4, and MUC20 was statistically significant. The expression of MUCl was related with the depth of invasion and clinical stage of SCC. The positive rates of MUC4 and MUC20 were associated with the degree of differentiation and clinical stage of SCC. There was a correlation between the expression of MUC4, MUC 1, and MUC20 in cervical squamous lesions. Mucins may be involved in the development of cervical cancer.

Effect of mTOR Inhibitors in Nude Mice with Endometrial Carcinoma and Variable PTEN Expression Status

PubMed Central

Fong, Pedro; Meng, Li-rong

2014-01-01

Background The aim of this study was to investigate the sensitivity to rapamycin of endometrial cancer cells with different phosphatase and tensin homologue (PTEN) expression to understand the mechanism of resistance to mammalian target of rapamycin (mTOR) inhibitors in the treatment of endometrial cancer. Material/Methods Twenty specific pathogen-free female BALB/c mice received transplants of either HEC-1A (PTEN-positive) or Ishikawa (PTEN-negative) cells. Mice in the treatment group were injected intraperitoneally once a week for 4 consecutive weeks. The control group was injected weekly with phosphate buffer saline (PBS) for 4 consecutive weeks. Tumor volume, tumor mass, growth curves, and inhibition rate were measured, after which the mice were killed. Results Both tumor growth rate and size were slower in the treatment group than in the control group for all mice that received transplants of either HEC-1A or Ishikawa cells. The tumor inhibition rates in the treatment group were 48.1% and 67.1% in mice transplanted with HEC-1A and Ishikawa cells, respectively. Conclusions The inhibitory effects of rapamycin were enhanced in PTEN-negative Ishikawa tumor cells compared with PTEN-positive HEC-1A cells, which could explain the reduced effect of rapalogues in some endometrial cancer patients and help to understand the mechanism of resistance to this drug. PMID:25266877

Distinct Developmental Origins Manifest in the Specialized Encoding of Movement by Adult Neurons of the External Globus Pallidus

PubMed Central

Dodson, Paul D.; Larvin, Joseph T.; Duffell, James M.; Garas, Farid N.; Doig, Natalie M.; Kessaris, Nicoletta; Duguid, Ian C.; Bogacz, Rafal; Butt, Simon J.B.; Magill, Peter J.

2015-01-01

Summary Transcriptional codes initiated during brain development are ultimately realized in adulthood as distinct cell types performing specialized roles in behavior. Focusing on the mouse external globus pallidus (GPe), we demonstrate that the potential contributions of two GABAergic GPe cell types to voluntary action are fated from early life to be distinct. Prototypic GPe neurons derive from the medial ganglionic eminence of the embryonic subpallium and express the transcription factor Nkx2-1. These neurons fire at high rates during alert rest, and encode movements through heterogeneous firing rate changes, with many neurons decreasing their activity. In contrast, arkypallidal GPe neurons originate from lateral/caudal ganglionic eminences, express the transcription factor FoxP2, fire at low rates during rest, and encode movements with robust increases in firing. We conclude that developmental diversity positions prototypic and arkypallidal neurons to fulfil distinct roles in behavior via their disparate regulation of GABA release onto different basal ganglia targets. PMID:25843402

Automatic emotion processing as a function of trait emotional awareness: an fMRI study

PubMed Central

Lichev, Vladimir; Sacher, Julia; Ihme, Klas; Rosenberg, Nicole; Quirin, Markus; Lepsien, Jöran; Pampel, André; Rufer, Michael; Grabe, Hans-Jörgen; Kugel, Harald; Kersting, Anette; Villringer, Arno; Lane, Richard D.

2015-01-01

It is unclear whether reflective awareness of emotions is related to extent and intensity of implicit affective reactions. This study is the first to investigate automatic brain reactivity to emotional stimuli as a function of trait emotional awareness. To assess emotional awareness the Levels of Emotional Awareness Scale (LEAS) was administered. During scanning, masked happy, angry, fearful and neutral facial expressions were presented to 46 healthy subjects, who had to rate the fit between artificial and emotional words. The rating procedure allowed assessment of shifts in implicit affectivity due to emotion faces. Trait emotional awareness was associated with increased activation in the primary somatosensory cortex, inferior parietal lobule, anterior cingulate gyrus, middle frontal and cerebellar areas, thalamus, putamen and amygdala in response to masked happy faces. LEAS correlated positively with shifts in implicit affect caused by masked happy faces. According to our findings, people with high emotional awareness show stronger affective reactivity and more activation in brain areas involved in emotion processing and simulation during the perception of masked happy facial expression than people with low emotional awareness. High emotional awareness appears to be characterized by an enhanced positive affective resonance to others at an automatic processing level. PMID:25140051

Mouse mammary tumour virus (MMTV) and human breast cancer with neuroendocrine differentiation.

PubMed

Js, Lawson; Cc, Ngan; Wk, Glenn; Dd, Tran

2017-01-01

Mouse mammary tumour viruses (MMTVs) may have a role in a subset of human breast cancers. MMTV positive human breast cancers have similar histological characteristics to neuroendocrine breast cancers and to MMTV positive mouse mammary tumours. The purpose of this study was to investigate the expression of neuroendocrine biomarkers - synaptophysin and chromogranin, to determine if these histological characteristics and biomarker expression were due to the influences of MMTV. Immunohistochemistry analyses to identify synaptophysin and chromogranin were conducted on a series of human breast cancers in which (i) MMTV had been previously identified and had similar histological characteristics to MMTV positive mouse mammary tumours and (ii) MMTV positive mouse mammary tumours. The expression of synaptophysin and chromogranin in MMTV positive mouse mammary tumors were all positive (7 of 7 specimens - 100% positive). The expression of synaptophysin and chromogranin in MMTV positive human breast cancers was much less prevalent (3 of 22 - 14%). There was no expression of synaptophysin and chromogranin in the normal breast tissue control specimens. It is not possible to draw any firm conclusions from these observations. However, despite the small numbers of MMTV positive mouse mammary tumours in this study, the universal expression in these specimens of synaptophysin and chromogranin proteins is striking. This pattern of synaptophysin and chromogranin expression is very different from their expression in MMTV positive human breast cancers. The reason for these differences is not known. The high prevalence of positive expression of synaptophysin and chromogranin in MMTV positive mouse mammary tumours and low expression of synaptophysin and chromogranin in MMTV positive human breast cancers indicates that MMTV is not usually associated with neuroendocrine human breast cancers.

Increased expression of sex determining region Y-box 11 (SOX11) in cutaneous malignant melanoma.

PubMed

Jian, Jiao; Guoying, Wang; Jing, Zhao

2013-08-01

To observe sex determining region Y-box 11 (SOX11) gene expression in cutaneous malignant melanoma and its effect on tumour cell proliferation. Clinicopathological data and tissue samples from patients with cutaneous malignant melanoma, together with tissue samples from healthy volunteers (controls), were retrospectively reviewed. Protein levels of SOX11 and the antigen identified by monoclonal antibody Ki-67 (Ki-67) in skin lesions were analysed using immunohistochemistry. The correlation between protein levels and clinipathological parameters was investigated. Out of 40 patient samples, 25 (62.5%) were positive for SOX11 protein in malignant melanoma tissue. This was significantly higher than in 40 control tissue samples, in which no SOX11 protein was detected. Presence of SOX11 protein was positively related to the proliferation index of cutaneous malignant melanoma tumour cells. Presence of SOX11 protein in cutaneous malignant melanoma was related to tumour type, tumour location, lymph node metastasis and 5-year survival rate. Human cutaneous malignant melanoma tissues expressed high levels of SOX11 compared with healthy controls, suggesting that SOX11 may be a new prognostic marker for malignant melanoma.

Decreased expression of the ATM gene linked to poor prognosis for gastric cancer of different nationalities in Xinjiang.

PubMed

Han, Mei; Ma, Lanying; Qu, Yanli; Tang, Yong

2017-08-01

To explore the clinicopathological significance of ATM gene in the occurrence and prognosis of gastric cancer (GC) from different nationalities in Xinjiang. The expression of ATM in 385 patients with GC (including 98 Uygurs, 231 Hans and 56 Kazaks) and its corresponding adjacent tissues were examined by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry assay to, analyze its correlations with clinicopathological features and prognosis of GC. The ATM expression in GC tissues was significantly decreased when compared to that in adjacent normal tissues of Uygur, Han and Kazak patients in Xinjiang, while Uygurs and Kazaks were much lower than Hans in the ATM expression of GC tissues (all P<0.05). Kaplan-Meier analysis showed that Uygur and Kazak patients with ATM-negative tumors had a markedly lower survival rate than patients in Hans (P=0.028), and GC patients with ATM negative expression presented more unfavorable overall survival rate than those with positive expression among the three different nationalities (all P<0.05). Multivariate Cox regression analysis revealed that nationality, ATM expression, TNM staging, depth of invasion, and lymph node metastasis were independent factors affecting the prognosis of GC patients in Xinjiang (all P<0.05). ATM was downregulated in GC patients in Xinjiang, especially for Uygurs and Kazaks, which suggested ATM to be an independent indicator of prognosis for GC therapy. Copyright © 2017 Elsevier GmbH. All rights reserved.

Detection of pAkt protein in imprint cytology of invasive breast cancer: Correlation with HER2/neu, hormone receptors, and other clinicopathological variables

PubMed Central

Vasou, Olympia; Skagias, Lazaros; Anastasia, Margariti; Paulina, Athanasiadou; Patsouris, Efstratios; Politi, Ekaterini

2015-01-01

Purpose: Akt is a serine/threonine protein kinase and has emerged as a crucial regulator of widely divergent cellular processes, including apoptosis, proliferation, differentiation, and metabolism. Activation of Akt/protein kinase B has been positively associated with human epidermal growth-factor receptor 2 (HER2)/neu overexpression in breast carcinoma and a worse outcome among endocrine treated patients. The Akt signaling pathway currently attracts considerable attention as a new target for effective therapeutic strategies. We therefore investigated the relationship between activation of Akt and clinicopathologic variables including hormone receptor and HER2/neu status. Methods: Archival tumor tissues from 100 patients with invasive breast carcinoma were analyzed by immunocytochemistry. This study describes the results of immunocytochemical pAkt expression in breast carcinoma imprints, prepared from cut surfaces of freshly removed tumors. Both nuclear and cytoplasmic expressions were evaluated for pAkt. Results: Nuclear and cytoplasmic positive scores of 72% (72/100) and 42% (42/100), respectively, were found. Coexistence of nuclear and cytoplasmic staining was observed in 32 cases (32/100). Nuclear positive staining correlated with HER2/neu overexpression (P = 0.043) and was significantly associated with positive involvement of axillary lymph nodes (P = 0.013). No correlation was found between cytoplasmic pAkt rate and clinicopathological parameters, estrogen receptor, progesterone receptor or HER2/neu expression. Conclusions: pAkt expression can be evaluated in cytological material and may add valuable information to current prognostic models for breast cancer. pAkt overexpression appears to be linked with potentially aggressive tumor phenotype in invasive breast carcinoma. PMID:25838835

Nuclear NF-κB Expression Correlates With Outcome Among Patients With Head and Neck Squamous Cell Carcinoma Treated With Primary Chemoradiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balermpas, Panagiotis; Michel, Yvonne; Wagenblast, Jens

2013-07-15

Background: To examine whether nuclear NF-κB expression correlates with outcome in patients with head and neck squamous cell carcinoma (HNSCC) treated with primary chemoradiation therapy (CRT). Methods and Materials: Between 2007 and 2010, 101 patients with locally advanced primary HNSCC were treated with definitive simultaneous CRT. Pretreatment biopsy specimens were analyzed for NF-κB p65 (RelA) nuclear immunoreactivity. A sample was assigned to be positive with more than 5% positive nuclear expression. The predictive relevance of NF-κB and clinicopathologic factors for overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS), and metastasis-free survival (DMFS) was examined by univariate and multivariatemore » analysis. Results: No significant differences between the groups were observed with regard to age, sex, total radiation dose, fractionation mode, total chemotherapy applied, T stage or grading. Patients with p65 nuclear positive biopsy specimens showed significantly a higher rate of lymph node metastasis (cN2c or cN3 status, P=.034). Within a mean follow-up time of 25 months (range, 2.33-62.96 months) OS, PFS, and DMFS were significantly poorer in the p65 nuclear positive group (P=.008, P=.027, and P=.008, respectively). These correlations remained significant in multivariate analysis. Conclusion: NF-κB/p65 nuclear expression is associated with increased lymphatic and hematogenous tumor dissemination and decreased survival in HNSCC patients treated with primary CRT. Our results may foster further investigation of a predictive relevance of NF-κB/p65 and its role as a suitable target for a molecular-based targeted therapy in HNSCC cancer.« less

Comparison of Akt/mTOR/4E-BP1 pathway signal activation and mutations of PIK3CA in Merkel cell polyomavirus-positive and Merkel cell polyomavirus-negative carcinomas.

PubMed

Iwasaki, Takeshi; Matsushita, Michiko; Nonaka, Daisuke; Kuwamoto, Satoshi; Kato, Masako; Murakami, Ichiro; Nagata, Keiko; Nakajima, Hideki; Sano, Shigetoshi; Hayashi, Kazuhiko

2015-02-01

Merkel cell polyomavirus (MCPyV) integrates monoclonally into the genomes of approximately 80% of Merkel cell carcinomas (MCCs), affecting their clinicopathological features. The molecular mechanisms underlying MCC development after MCPyV infection remain unclear. We investigated the association of MCPyV infection with activation of the Akt/mammalian target of rapamycin (mTOR)/4E-binding protein 1 (4E-BP1) signaling pathway in MCCs to elucidate the role of these signal transductions and to identify molecular targets for treatment. We analyzed the molecular and pathological characteristics of 41 MCPyV-positive and 27 MCPyV-negative MCCs. Expression of mTOR, TSC1, and TSC2 messenger RNA was significantly higher in MCPyV-negative MCCs, and Akt (T308) phosphorylation also was significantly higher (92% vs 66%; P = .019), whereas 4E-BP1 (S65 and T70) phosphorylation was common in both MCC types (92%-100%). The expression rates of most other tested signals were high (60%-100%) and not significantly correlated with MCPyV large T antigen expression. PIK3CA mutations were observed more frequently in MCPyV-positive MCCs (6/36 [17%] vs 2/20 [10%]). These results suggest that protein expression (activation) of most Akt/mTOR/4E-BP1 pathway signals was not significantly different in MCPyV-positive and MCPyV-negative MCCs, although these 2 types may differ in tumorigenesis, and MCPyV-negative MCCs showed significantly more frequent p-Akt (T308) activation. Therefore, certain Akt/mTOR/4E-BP1 pathway signals could be novel therapeutic targets for MCC regardless of MCPyV infection status. Copyright © 2015 Elsevier Inc. All rights reserved.

Evidence of Rapid Modulation by Social Information of Subjective, Physiological, and Neural Responses to Emotional Expressions

PubMed Central

Mermillod, Martial; Grynberg, Delphine; Pio-Lopez, Léo; Rychlowska, Magdalena; Beffara, Brice; Harquel, Sylvain; Vermeulen, Nicolas; Niedenthal, Paula M.; Dutheil, Frédéric; Droit-Volet, Sylvie

2018-01-01

Recent research suggests that conceptual or emotional factors could influence the perceptual processing of stimuli. In this article, we aimed to evaluate the effect of social information (positive, negative, or no information related to the character of the target) on subjective (perceived and felt valence and arousal), physiological (facial mimicry) as well as on neural (P100 and N170) responses to dynamic emotional facial expressions (EFE) that varied from neutral to one of the six basic emotions. Across three studies, the results showed reduced ratings of valence and arousal of EFE associated with incongruent social information (Study 1), increased electromyographical responses (Study 2), and significant modulation of P100 and N170 components (Study 3) when EFE were associated with social (positive and negative) information (vs. no information). These studies revealed that positive or negative social information reduces subjective responses to incongruent EFE and produces a similar neural and physiological boost of the early perceptual processing of EFE irrespective of their congruency. In conclusion, the article suggests that the presence of positive or negative social context modulates early physiological and neural activity preceding subsequent behavior. PMID:29375330

Criteria for acceptable levels of the Shinkansen Super Express train noise and vibration in residential areas

NASA Astrophysics Data System (ADS)

Yamanaka, K.; Nakagawa, T.; Kobayashi, F.; Kanada, S.; Tanahashi, M.; Muramatsu, T.; Yamada, S.

1982-10-01

A survey of 1187 housewives living in 18 areas along the Shinkansen Super Express (bullet train) railway was conducted by means of a self-administered health questionnaire (modified Cornell Medical Index). In addition, geographically corresponding measurements of noise level and vibration intensity were taken. The relationship of noise and vibration to positive responses (health complaints) related to bodily symptoms, illness and emotional disturbances was analyzed. The factors which correlated with an increase in the average number of positive responses included noise, vibration, age and health status. Such factors as marital status, educational level, part time work, duration of inhabitancy and occupation of the head of the houshold correlated poorly with the number of positive responses. Unhealthy respondents compared to healthy respondents are more frequently affected by noise and vibration. The rate of positive responses in the visual, respiratory, cardiovascular, digestive and nervous systems, sleep disturbances and emotional disturbances increased accordingly as noise and vibration increased. Combined effects of noise and vibration stimuli on the total number of positive responses (an indicator of general health) were found. This study has produced results indicating that the maximum permissible noise level should not exceed 70 dB(A) in the residential areas along the Shinkansen railway.

Upregulation of Integrin-α6 and Integrin-β1 Gene Expressions in Mouse Spermatogonial Stem Cells after Continues and Pulsed Low Intensity Ultrasound Stimulation

PubMed Central

Mohaqiq, Mahdi; Movahedin, Mansoureh; Mokhtari Dizaji, Manijhe; Mazaheri, Zohreh

2018-01-01

Objective low intensity ultrasound (continues and pulsed) is a form of energy. Spermatogonial stem cells (SSCs) are at the base of male fertility. This study investigated the effects of low intensity ultrasound stimulation (LIUS) and low intensity pulsed ultrasound stimulation (LIUPS) on the expression of germ cell-specific and pluripotency genes in SSCs in vitro. Materials and Methods In this experimental study, isolated SSCs from neonatal male mice were cultured in Dulbecco’s Modified Eagle’s Medium (DMEM) with 10% fetal bovine serum (FBS). In addition, to confirm identification of SSCs, PLZF protein was detected positively in SSCs derived colonies. SSCs were stimulated by LIUS and LIUPS for 5 days, followed by assessment of expression of integrin-α6 (Itga6) and β1 (Itgβ1), as two germ cell-specific genes, and Oct- 4, as a pluripotency gene, on day 21st by quantitive reverse transcriptase-polymerase chain reaction (qRT-PCR). To investigate the proliferation rate and colonization of SSCs in different groups, counting whole number of the cells and colonies as well as analysis of the respective diameters were performed on days 7th, 14th and 21st. Data was analyzed by ANOVA test. Results LIUS and LIUPS treatment of mouse SSCs increased expression of Itga6 and Itgβ1 genes in the experimental groups, compared to the control group (P<0.05), whereas there was no significant difference between the groups, regarding the expression of Oct-4 gene. These treatments maintained survival rate, while they increased proliferation rate and colonization of SSCs during the first week of culture. However, within the second week, proliferation rate and colonization were decreased in the experimental groups. Conclusion These results suggested that LIUS and LIUPS treatment had good effect on SSCs proliferation and colonization, based on the gene-specific marker expression during 21 days culture in vitro. PMID:29105399

Phosphorylated AMP-activated protein kinase expression associated with prognosis for patients with gastric cancer treated with cisplatin-based adjuvant chemotherapy.

PubMed

Kang, Byung Woog; Jeong, Ji Yun; Chae, Yee Soo; Lee, Soo Jung; Lee, Yoo Jin; Choi, Jun Young; Lee, In-Kyu; Jeon, Seong Woo; Bae, Han Ik; Lee, Da Keun; Kwon, Oh-Kyoung; Chung, Ho Young; Yu, Wansik; Kim, Jong Gwang

2012-11-01

The present study analyzed the expression of phosphorylated AMP-activated protein kinase (pAMPK), Fyn kinase, and pyruvate dehydrogenase kinase-1 (PDK-1) and their impact on the survival of patients with resected gastric cancer who received cisplatin-based adjuvant chemotherapy. Korean patients with stage II-IV (M0) gastric adenocarcinoma who underwent a gastrectomy with D2 lymph node resection and received a combination regimen of cisplatin and S-1 were enrolled. Immunohistochemistry was carried out to determine the expression of pAMPK, Fyn kinase, and PDK-1 in operative specimens of gastric cancer. The expression was divided into two groups according to the intensity score (negative: 0 or 1+ and positive: 2+ or 3+). From January 2006 to July 2010, 73 tumor samples obtained from 74 patients were analyzed. Forty patients were included in the pAMPK-positive group, while 33 patients were included in the pAMPK-negative group. Meanwhile, positive Fyn kinase expression was observed in only 10 patients (13.7 %), and there was no or very weak PDK-1 staining. The clinicopathologic characteristics were similar between the two groups according to the expression of pAMPK. With a median follow-up duration of 26.5 months (2.6-73.2), the estimated 3-year relapse-free survival (RFS) and overall survival rates were 55.0 and 78.4 %, respectively. In a multivariate analysis adjusted for age, sex, Lauren classification, and stage, the pAMPK-negative group was significantly associated with improved RFS (Hazard ratio = 0.459, 95 % CI 0.109-0.711, P = 0.043). A low expression of pAMPK was found to be correlated with better RFS in patients with resected gastric cancer treated with adjuvant cisplatin-based chemotherapy.

Expression and prognostic value of soluble CD97 and its ligand CD55 in intrahepatic cholangiocarcinoma.

PubMed

Meng, Ze-Wu; Liu, Min-Chao; Hong, Hai-Jie; Du, Qiang; Chen, Yan-Ling

2017-03-01

The incidence rate of intrahepatic cholangiocarcinoma is rising, and treatment options are limited. Therefore, new biological markers of intrahepatic cholangiocarcinoma are needed. Immunohistochemistry and enzyme-linked immunosorbent assay were applied to analyze the expressions of CD97, CD55, and soluble CD97 in 71 patients with intrahepatic cholangiocarcinoma and 10 patients with hepatolithiasis. CD97 and CD55 were not expressed in hepatolithiatic tissues, but positive expression was observed in 76.1% (54/71) and 70.4% (50/71) of intrahepatic cholangiocarcinoma patients. The univariate analyses indicated that the positive expressions of CD97 and CD55 were related to short intrahepatic cholangiocarcinoma survival of patients (both p = 0.001). Furthermore, CD97 and CD55 expressions and biliary soluble CD97 levels were significantly associated with histological grade (p = 0.004, 0.002, and 0.012, respectively), lymph node metastases (p = 0.020, 0.038, and 0.001, respectively), and venous invasion (p = 0.003, 0.002, and 0.001, respectively). The multivariate analyses indicated that lymph node metastases (hazard ratio: 2.407, p = 0.003), positive CD55 expression (hazard ratio: 4.096, p = 0.003), and biliary soluble CD97 levels (hazard ratio: 2.434, p = 0.002) were independent risk factors for the intrahepatic cholangiocarcinoma survival. The receiver operating characteristic (ROC) curve analysis indicated that when the cutoff values of biliary soluble CD97 were 1.15 U/mL, the diagnostic value for predicting lymph node metastasis had a sensitivity of 87.5% and a specificity of 51.3%. For intrahepatic cholangiocarcinoma patient death within 60 months at a cutoff value of 0.940 U/mL, the diagnostic value sensitivity was 89.3% and the specificity was 93.3%. Biliary soluble CD97 may be a new biological marker for early diagnosis, prediction of lymph node metastasis and poor prognosis, and discovery of a therapeutic target.

The Developmental Progression of Understanding of Mind during a Hiding Game

PubMed Central

Nelson, P. Brooke; Adamson, Lauren B.; Bakeman, Roger

2011-01-01

In this longitudinal study, 52 typically developing preschoolers engaged in a hiding game with their mothers when children were 42-, 54-, and 66-months old. Children's understanding of mind, positive affect, and engagement with the task were rated, and mothers' utterances were coded for role and content. Analyses confirmed that some facets of children's understanding of mind developed sequentially; specifically, they expressed an understanding of knowledge access before an understanding of deception and false beliefs, and expressed an understanding of deception before an understanding of false beliefs. Children's understanding of mind increased across visits and positively correlated with false belief task performance. Results suggest that mothers may tailor the content of their utterances to the child's growing expertise, but the role of mothers' utterances did not change. Observing preschoolers engaged in a playful hiding game revealed that children's understanding of mind not only increased with age but also developed sequentially. PMID:25960610

The expression and underlying angiogenesis effect of DPC4 and VEGF on the progression of cervical carcinoma

PubMed Central

A, Yanni; Li, Ying; Zhao, Shuping

2018-01-01

The present study aimed to investigate the expression and roles of deleted in pancreatic carcinoma locus 4 (DPC4) and vascular endothelial growth factor (VEGF) in the development of cervical carcinoma. A total of 115 patients aged between 25 and 60 years were involved, including 19 cervical inflammation, 35 cervical intraepithelial neoplasia (CIN), and 61 cervical squamous-cell carcinoma (CSCC). The protein expression rates of DPC4 and VEGF in all samples were detected using immunohistochemistry. The protein levels of DPC4 and VEGF in CSCC samples were measured using ELISA. Microvessel density (MVD) of each CSCC sample was measured according to the Winder method. Association analysis between DPC4, VEGF and thrombospondin-1 (TSP-1) was conducted using Spearman's correlations. The negative expression rate of DPC4 [DPC4 (−)] and positive expression rate of VEGF [VEGF (+)] of the CSCC group were significantly higher compared with that in the cervical inflammation and CIN groups (P<0.05). In the CSCC group, the protein level of DPC4 decreased, while the VEGF level increased significantly compared with the healthy control group (P<0.05). The MVD in the DPC4 (−), VEGF (+) and TSP-1 (−) groups was significantly increased compared with that of the DPC4 (+), VEGF (−), and TSP-1 (+) groups (P<0.05). The expression of DPC4 was negatively associated with VEGF and TSP-1 (P<0.01). These results suggest that DPC4, VEGF and TSP-1 are involved in the carcinogenesis of cervical carcinoma by inducing angiogenesis. In addition, the loss of DPC4 induces angiogenesis through increasing VEGF. Thus, VEGF may be a target gene regulated by DPC4. PMID:29434970

The expression and underlying angiogenesis effect of DPC4 and VEGF on the progression of cervical carcinoma.

PubMed

A, Yanni; Li, Ying; Zhao, Shuping

2018-02-01

The present study aimed to investigate the expression and roles of deleted in pancreatic carcinoma locus 4 (DPC4) and vascular endothelial growth factor (VEGF) in the development of cervical carcinoma. A total of 115 patients aged between 25 and 60 years were involved, including 19 cervical inflammation, 35 cervical intraepithelial neoplasia (CIN), and 61 cervical squamous-cell carcinoma (CSCC). The protein expression rates of DPC4 and VEGF in all samples were detected using immunohistochemistry. The protein levels of DPC4 and VEGF in CSCC samples were measured using ELISA. Microvessel density (MVD) of each CSCC sample was measured according to the Winder method. Association analysis between DPC4, VEGF and thrombospondin-1 (TSP-1) was conducted using Spearman's correlations. The negative expression rate of DPC4 [DPC4 (-)] and positive expression rate of VEGF [VEGF (+)] of the CSCC group were significantly higher compared with that in the cervical inflammation and CIN groups (P<0.05). In the CSCC group, the protein level of DPC4 decreased, while the VEGF level increased significantly compared with the healthy control group (P<0.05). The MVD in the DPC4 (-), VEGF (+) and TSP-1 (-) groups was significantly increased compared with that of the DPC4 (+), VEGF (-), and TSP-1 (+) groups (P<0.05). The expression of DPC4 was negatively associated with VEGF and TSP-1 (P<0.01). These results suggest that DPC4, VEGF and TSP-1 are involved in the carcinogenesis of cervical carcinoma by inducing angiogenesis. In addition, the loss of DPC4 induces angiogenesis through increasing VEGF. Thus, VEGF may be a target gene regulated by DPC4.

Normal distribution and medullary-to-cortical shift of Nestin-expressing cells in acute renal ischemia.

PubMed

Patschan, D; Michurina, T; Shi, H K; Dolff, S; Brodsky, S V; Vasilieva, T; Cohen-Gould, L; Winaver, J; Chander, P N; Enikolopov, G; Goligorsky, M S

2007-04-01

Nestin, a marker of multi-lineage stem and progenitor cells, is a member of intermediate filament family, which is expressed in neuroepithelial stem cells, several embryonic cell types, including mesonephric mesenchyme, endothelial cells of developing blood vessels, and in the adult kidney. We used Nestin-green fluorescent protein (GFP) transgenic mice to characterize its expression in normal and post-ischemic kidneys. Nestin-GFP-expressing cells were detected in large clusters within the papilla, along the vasa rectae, and, less prominently, in the glomeruli and juxta-glomerular arterioles. In mice subjected to 30 min bilateral renal ischemia, glomerular, endothelial, and perivascular cells showed increased Nestin expression. In the post-ischemic period, there was an increase in fluorescence intensity with no significant changes in the total number of Nestin-GFP-expressing cells. Time-lapse fluorescence microscopy performed before and after ischemia ruled out the possibility of engraftment by the circulating Nestin-expressing cells, at least within the first 3 h post-ischemia. Incubation of non-perfused kidney sections resulted in a medullary-to-cortical migration of Nestin-GFP-positive cells with the rate of expansion of their front averaging 40 microm/30 min during the first 3 h and was detectable already after 30 min of incubation. Explant matrigel cultures of the kidney and aorta exhibited sprouting angiogenesis with cells co-expressing Nestin and endothelial marker, Tie-2. In conclusion, several lines of circumstantial evidence identify a sub-population of Nestin-expressing cells with the mural cells, which are recruited in the post-ischemic period to migrate from the medulla toward the renal cortex. These migrating Nestin-positive cells may be involved in the process of post-ischemic tissue regeneration.

[Expression and clinical significance of Pokemon in non-small cell lung cancer].

PubMed

Zhao, Zhihong; Wang, Shengfa; Zhang, Tiewa

2007-12-20

Proto-oncogene Pokemon is the special transcription inhibitor of ARF,which can regulate cell growth and differentiation by ARF-P53 path.It may be the important monitoring target of tumor because of being upstream region of many tumor suppressor genes and proto-oncogenes.The aim of this study is to explore the clinical significance of Pokemon gene in non-small cell lung cancer(NSCLC). Immunohistochemistry was applied to detect the expression of Pokemon protein in 92 cases of NSCLC and 20 cases of paracancerous lung tissues.Correlation between abnormal expression of Pokemon with pathologic characteristics and prognosis of NSCLC was analyzed. Pokemon was not expressed in paracancerous lung tissues and was found in 66 of 92(71.7%) cases of lung cancer tissues.Expression of Pokemon was closely related to TNM stages(P=0.011).Survival rate of patients with negative Pokemon expression was significantly higher than that of those with positive Pokemon expression(P=0.0015).Pokemon expression was demonstrated as independent prognostic factor of NSCLC. Pokemon is expressed in NSCLC and it may be identified as a new diagnostic marker.High expression of Pokemon may indicate poor prognosis of patients with NSCLC.

Effect of Curcuma longa and Ocimum sanctum on myocardial apoptosis in experimentally induced myocardial ischemic-reperfusion injury

PubMed Central

Mohanty, Ipseeta; Arya, Dharamvir Singh; Gupta, Suresh Kumar

2006-01-01

Background In the present investigation, the effect of Curcuma longa (Cl) and Ocimum sanctum (Os) on myocardial apoptosis and cardiac function was studied in an ischemia and reperfusion (I-R) model of myocardial injury. Methods Wistar albino rats were divided into four groups and orally fed saline once daily (sham, control IR) or Cl (100 mg/kg; Cl-IR) or Os (75 mg/kg; Os-IR) respectively for 1 month. On the 31st day, in the rats of the control IR, Cl-IR and Os-IR groups LAD occlusion was undertaken for 45 min, and reperfusion was allowed for 1 h. The hemodynamic parameters{mean arterial pressure (MAP), heart rate (HR), left ventricular end-diastolic pressure (LVEDP), left ventricular peak positive (+) LVdP/dt (rate of pressure development) and negative (-) LVdP/dt (rate of pressure decline)} were monitored at pre-set points throughout the experimental duration and subsequently, the animals were sacrificed for immunohistopathological (Bax, Bcl-2 protein expression & TUNEL positivity) and histopathological studies. Results Chronic treatment with Cl significantly reduced TUNEL positivity (p < 0.05), Bax protein (p < 0.001) and upregulated Bcl-2 (p < 0.001) expression in comparison to control IR group. In addition, Cl demonstrated mitigating effects on several myocardial injury induced hemodynamic {(+)LVdP/dt, (-) LVdP/dt & LVEDP} and histopathological perturbations. Chronic Os treatment resulted in modest modulation of the hemodynamic alterations (MAP, LVEDP) but failed to demonstrate any significant antiapoptotic effects and prevent the histopathological alterations as compared to control IR group. Conclusion In the present study, significant cardioprotection and functional recovery demonstrated by Cl may be attributed to its anti-apoptotic property. In contrast to Os, Cl may attenuate cell death due to apoptosis and prevent the impairment of cardiac performance. PMID:16504000

Evaluation of prognostic and predictive value of microtubule associated protein tau in two independent cohorts.

PubMed

Baquero, Maria T; Lostritto, Karen; Gustavson, Mark D; Bassi, Kimberly A; Appia, Franck; Camp, Robert L; Molinaro, Annette M; Harris, Lyndsay N; Rimm, David L

2011-11-02

Microtubule associated proteins (MAPs) endogenously regulate microtubule stabilization and have been reported as prognostic and predictive markers for taxane response. The microtubule stabilizer, MAP-tau, has shown conflicting results. We quantitatively assessed MAP-tau expression in two independent breast cancer cohorts to determine prognostic and predictive value of this biomarker. MAP-tau expression was evaluated in the retrospective Yale University breast cancer cohort (n = 651) using tissue microarrays and also in the TAX 307 cohort, a clinical trial randomized for TAC versus FAC chemotherapy (n = 140), using conventional whole tissue sections. Expression was measured using the AQUA method for quantitative immunofluorescence. Scores were correlated with clinicopathologic variables, survival, and response to therapy. Assessment of the Yale cohort using Cox univariate analysis indicated an improved overall survival (OS) in tumors with a positive correlation between high MAP-tau expression and overall survival (OS) (HR = 0.691, 95% CI = 0.489-0.974; P = 0.004). Kaplan Meier analysis showed 10-year survival for 65% of patients with high MAP-tau expression compared to 52% with low expression (P = .006). In TAX 307, high expression was associated with significantly longer median time to tumor progression (TTP) regardless of treatment arm (33.0 versus 23.4 months, P = 0.010) with mean TTP of 31.2 months. Response rates did not differ by MAP-tau expression (P = 0.518) or by treatment arm (P = 0.584). Quantitative measurement of MAP-tau expression has prognostic value in both cohorts, with high expression associated with longer TTP and OS. Differences by treatment arm or response rate in low versus high MAP-tau groups were not observed, indicating that MAP-tau is not associated with response to taxanes and is not a useful predictive marker for taxane-based chemotherapy.

Prognostic value of survivin expression in parotid gland cancer in consideration of different histological subtypes.

PubMed

Stenner, Markus; Demgensky, Ariane; Molls, Christoph; Hardt, Aline; Luers, Jan C; Grosheva, Maria; Huebbers, Christian U; Klussmann, Jens P

2011-05-01

Cancer of the major salivary glands comprises a morphological diverse group of rare tumours of largely unknown cause. Survivin, an inhibitor of apoptosis has shown to be a significant prognostic indicator in various human cancers. The aim of this study was to assess the long-term prognostic value of survivin in a large group of histological different salivary gland cancers. We analysed the survivin expression in 143 patients with parotid gland cancer by means of immunohistochemistry and tissue micro array. Survivin expression was categorised into a low and a high expressing group. The experimental findings were correlated with clinicopathological and survival parameters. The mean follow-up time was 54.8 months. A positive cytoplasmic expression of survivin was found in 61.5%, a high expression in 25.9% of all specimens. In the whole group, high cytoplasmic survivin expression significantly indicated a poor 5-year disease-free and overall survival rate (p < 0.0001, p = 0.003). This applied for all adeno-, adenoid cystic and undifferentiated carcinomas whereas in mucoepidermoid carcinomas an analogical non-significant trend could be observed. A high cytoplasmic survivin expression significantly indicated a poor survival in high grade but not in low grade tumours. A multivariate analysis revealed that high cytoplasmic survivin expression was the only significant negative prognostic indicator for a poor 5-year disease-free survival rate in all patients (p = 0.042). The correlation between cytoplasmic survivin expression and survival probabilities of salivary gland cancer might make this an effective tool in patient follow-up, prognosis and targeted therapy in future. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Expression of molecular markers detected by immunohistochemistry and risk of lymph node metastasis in stage T1 and T2 colorecrectal cancers].

PubMed

Wang, Fu-long; Wan, De-sen; Lu, Zhen-hai; Fang, Yu-jing; Li, Li-ren; Chen, Gong; Wu, Xiao-jun; Ding, Pei-rong; Kong, Ling-heng; Lin, Jun-zhong; Pan, Zhi-zhong

2013-04-01

To study the molecular risk factors of lymph node metastasis in stage T1 and T2 colorectal cancers by tissue microarray and immunohistochemistry techniques. Two hundred and three patients with stage T1 and T2 colorectal carcinoma who underwent radical surgery from 1999 to 2010 in our department were included in this study. Their clinicopathological data were retrospectively analyzed. Expression of the following 14 molecular markers were selected and assayed by tissue microarray and immunohistochemistry: VEGFR-3, HER2, CD44v6, CXCR4, TIMP-1, EGFR, IGF-1R, IGF-2, IGFBP-1, ECAD, MMP-9, RKIP, CD133, MSI. Chi-squared test and logistic regression were used to evaluate the variables as potential risk factors for lymph node metastasis. The positive expression rates of biomarkers were as following: VEGFR-3 (44.3%), EGFR (30.5%), HER-2 (28.1%), IGF-1R (63.5%), IGF-2 (44.8%), IGFBP-1 (70.9%), ECAD (45.8%), CD44v6 (51.2%), MMP-9 (44.3%), TIMP-1 (41.4%), RKIP (45.3%), CXCR4 (40.9%), and CD133 (49.8%). The positive rate of MSI expression was 22.2%. Both univariate and multivariate analyses showed that VEGFR-3, HER-2, and TIMP-1 were significant predictors of lymph node metastasis. Univariate analysis showed that CD44v6 and CXCR4 were significant significant predictors of lymph node metastasis. VEGFR-3, HER2 and TIMP-1 are independent factors for lymph node metastasis in stage T1 and T2 colorectal cancers.

[Study on anti-tumor effect of cyanidin-3-glucoside on ovarian cancer].

PubMed

Zeng, Linchai; Gao, Jie; Zhang, Rui

2012-06-01

To investigate the effect and the mechanism of cyanidin-3-glucoside (C3G) in the growth inhibition of ovarian cancer in vitro and in vivo. After human ovarian cancer cell line HO-8910PM was treated with C3G, cell growth was determined by the Cell Counting Kit-8 (CCK-8) assay and apoptosis was evaluated by flow cytometry analysis stained with Annexin V-FITC/PI. The protein expression in HO-8910PM cells was analyzed by Western blot assay. HO-8910PM cells were injected subcutaneously into nude mice to establish xenograft model. After 3 weeks of implantation, mice were randomized into 2 groups (n = 8): control group, feed with 0.2 mL double distilled water; C3G group, feed with C3G at a dose of 5 mg x kg(-1). All treatment lasted for two weeks, thrice per week. Eight weeks after implantation, tumor weight and inhibition rate were evaluated respectively after the mice were sacrificed. Immunohistochemistry was used to detect the positive expression of Ki-67 and Mucin-4 in the tumors. The proliferation of ovarian cancer cells was inhibited significantly by C3G with IC50 being 13.82 mg x L(-1). Apoptosis rate induced by C3G was markedly highter than that of control. The expression of Mucin4 was down-regulated in HO-8910PM cells after treatment of C3G. C3G inhibited the growth of ovarian xenograft tumors in nude mice. Furthermore, the positive expression of Ki-67 and Mucin-4 were both decreased in tumors after administration of C3G. C3G exerts anti-tumor activity in ovarian cancer both in vitro and in vivo, which may be related to down-regulation of Mucin-4 protein.

Expression and phosphorylation of the AS160_v2 splice variant supports GLUT4 activation and the Warburg effect in multiple myeloma

PubMed Central

2013-01-01

Background Multiple myeloma (MM) is a fatal plasma cell malignancy exhibiting enhanced glucose consumption associated with an aerobic glycolytic phenotype (i.e., the Warburg effect). We have previously demonstrated that myeloma cells exhibit constitutive plasma membrane (PM) localization of GLUT4, consistent with the dependence of MM cells on this transporter for maintenance of glucose consumption rates, proliferative capacity, and viability. The purpose of this study was to investigate the molecular basis of constitutive GLUT4 plasma membrane localization in MM cells. Findings We have elucidated a novel mechanism through which myeloma cells achieve constitutive GLUT4 activation involving elevated expression of the Rab-GTPase activating protein AS160_v2 splice variant to promote the Warburg effect. AS160_v2-positive MM cell lines display constitutive Thr642 phosphorylation, known to be required for inactivation of AS160 Rab-GAP activity. Importantly, we show that enforced expression of AS160_v2 is required for GLUT4 PM translocation and activation in these select MM lines. Furthermore, we demonstrate that ectopic expression of a full-length, phospho-deficient AS160 mutant is sufficient to impair constitutive GLUT4 cell surface residence, which is characteristic of MM cells. Conclusions This is the first study to tie AS160 de-regulation to increased glucose consumption rates and the Warburg effect in cancer. Future studies investigating connections between the insulin/IGF-1/AS160_v2/GLUT4 axis and FDG-PET positivity in myeloma patients are warranted and could provide rationale for therapeutically targeting this pathway in MM patients with advanced disease. PMID:24280290

Clinical significance of erythropoietin receptor expression in oral squamous cell carcinoma

PubMed Central

2012-01-01

Background Hypoxic tumors are refractory to radiation and chemotherapy. High expression of biomarkers related to hypoxia in head and neck cancer is associated with a poorer prognosis. The present study aimed to evaluate the clinicopathological significance of erythropoietin receptor (EPOR) expression in oral squamous cell carcinoma (OSCC). Methods The study included 256 patients who underwent primary surgical resection between October 1996 and August 2005 for treatment of OSCC without previous radiotherapy and/or chemotherapy. Clinicopathological information including gender, age, T classification, N classification, and TNM stage was obtained from clinical records and pathology reports. The mRNA and protein expression levels of EPOR in OSCC specimens were evaluated by Q-RT-PCR, Western blotting and immunohistochemistry assays. Results We found that EPOR were overexpressed in OSCC tissues. The study included 17 women and 239 men with an average age of 50.9 years (range, 26–87 years). The mean follow-up period was 67 months (range, 2–171 months). High EPOR expression was significantly correlated with advanced T classification (p < 0.001), advanced TNM stage (p < 0.001), and positive N classification (p = 0.001). Furthermore, the univariate analysis revealed that patients with high tumor EPOR expression had a lower 5-year overall survival rate (p = 0.0011) and 5-year disease-specific survival rate (p = 0.0017) than patients who had low tumor levels of EPOR. However, the multivariate analysis using Cox’s regression model revealed that only the T and N classifications were independent prognostic factors for the 5-year overall survival and 5-year disease-specific survival rates. Conclusions High EPOR expression in OSCC is associated with an aggressive tumor behavior and poorer prognosis in the univariate analysis among patients with OSCC. Thus, EPOR expression may serve as a treatment target for OSCC in the future. PMID:22639817

Nuclear localisation of LASP-1 correlates with poor long-term survival in female breast cancer.

PubMed

Frietsch, J J; Grunewald, T G P; Jasper, S; Kammerer, U; Herterich, S; Kapp, M; Honig, A; Butt, E

2010-05-25

LIM and SH3 protein 1 (LASP-1) is a nucleo-cytoplasmatic signalling protein involved in cell proliferation and migration and is upregulated in breast cancer in vitro studies have shown that LASP-1 might be regulated by prostate-derived ETS factor (PDEF), p53 and/or LASP1 gene amplification. This current study analysed the prognostic significance of LASP-1 on overall survival (OS) in 177 breast cancer patients and addressed the suggested mechanisms of LASP-1-regulation. Nucleo-cytoplasmatic LASP-1-positivity of breast carcinoma samples was correlated with long-term survival, clinicopathological parameters, Ki67-positivity and PDEF expression. Rate of LASP1 amplification was determined in micro-dissected primary breast cancer cells using quantitative RT-PCR. Cell-phase dependency of nuclear LASP-1-localisation was studied in synchronised cells. In addition, LASP-1, PDEF and p53 expression was compared in cell lines of different tumour entities to define principles for LASP-1-regulation. We showed that LASP-1 overexpression is not due to LASP1 gene amplification. Moreover, no correlation between p53-mutations or PDEF-expression and LASP-1-status was observed. However, nuclear LASP-1-localisation in breast carcinomas is increased during proliferation with peak in G2/M-phase and correlated significantly with Ki67-positivity and poor OS. Our results provide evidence that nuclear LASP-1-positivity may serve as a negative prognostic indicator for long-term survival of breast cancer patients.

[Effect of tagalsin on p53 and Bcl-2 expression in hepatoma H(22) tumor-bearing mice].

PubMed

Song, Xiu-qi; Guo, Yun-liang; Wang, Bing-gao; Sun, Shao-jie; Yao, Ru-yong

2011-07-01

To explore the effect and mechanism of tagalsin on hepatoma cells. The animal models were established by transplanting H(22) mouse hepatoma cells to mouse liver, and ten days later the mice were randomly divided into five groups: blank group, carmofur positive group and tagalsin groups, including low-dose, middle-dose and high-dose groups. Then medicine or oil was given to the mice by gastric gavage in consecutive 5 days with a 2-days interval as a course of treatment, two courses in all. All mice were killed at 24 hours after medication, and the survival period, ascites conditions, aggressive conditions intra- or extra-liver, weight changes, tumor volume and spleen index of the tumor-bearing mice were observed. Pathological changes of the tumors were examined. Apoptotic factors p53 and Bcl-2 protien and mRNA were detected by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). tagalsin inhibited the hepatoma growth effectively without influencing spleen index to some extent. The tumor inhibition rate of tagalsin low, middle and high dose groups were 17.9%, 63.1% and 71.8%, respectively. Immunohistochemical results showed that the p53 and Bcl-2 protein positive cell counts of the positive control and experimental groups were significantly lower than those of the blank group (P < 0.01). RT-PCR results showed that the p53 mRNA expression was significantly enhanced and Bcl-2 mRNA expression was decreased in the positive control groups and tagalsin treatment groups, especially in the high dose group, compared with those of the blank group (P < 0.05). tagalsin can inhibit the growth of mouse hepatoma cells significantly. The mechanism of its anti-tumor effect may work via up-regulating the wild type p53 gene expression and down-regulating Bcl-2 gene expression and thus regulating tumor cell apoptosis.

Role of fractalkine/CX3CR1 signaling pathway in the recovery of neurological function after early ischemic stroke in a rat model.

PubMed

Liu, Yan-Zhi; Wang, Chun; Wang, Qian; Lin, Yong-Zhong; Ge, Yu-Song; Li, Dong-Mei; Mao, Geng-Sheng

2017-09-01

This study aims to explore the role of fractalkine/CX3C chemokine receptor 1 (CX3CR1) signaling pathway in the recovery of neurological functioning after an early ischemic stroke in rats. After establishment of permanent middle cerebral artery occlusion (pMCAO) models, 50 rats were divided into blank, sham, model, positive control and CX3CR1 inhibitor groups. Neurological impairment, walking and grip abilities, and cortical and hippocampal infarctions were evaluated by Zea Longa scoring criterion, beam-walking assay and grip strength test, and diffusion-weighted magnetic resonance imaging. qRT-PCR and Western blotting were performed to detect mRNA and protein expressions. ELISA was conducted to measure concentration of sFractalkine (sFkn), interleukin-1β (IL-1β) and TNF-α. The recovery rate of neurological functioning impairment and reduced walking and grip abilities was faster in the positive control and CX3CR1 inhibitor groups than the model group. The model, positive control and CX3CR1 inhibitor groups showed increased mRNA and protein expression of chemokine C-X3-C motif ligand 1 (CX3CL1) and CX3CR1, concentration of sFkn, IL-1β and TNF-α, and size of cortical and cerebral infarctions while decreased expression of NGF and BDNF compared with the blank and sham groups. Compared with the model group, the mRNA and protein expression of CX3CL1 and CX3CR1, concentration of sFkn, IL-1β and TNF-α, and size of cortical and cerebral infarctions decreased while expression of NGF and BDNF increased in the positive control and CX3CR1 inhibitor groups. Thus, the study suggests that inhibition of fractalkine/CX3CR1 signaling pathway promotes the recovery of neurological functioning after the occurrence of an early ischemic stroke. Copyright © 2017 Elsevier Inc. All rights reserved.

Empathy, Challenge, and Psychophysiological Activation in Therapist–Client Interaction

PubMed Central

Voutilainen, Liisa; Henttonen, Pentti; Kahri, Mikko; Ravaja, Niklas; Sams, Mikko; Peräkylä, Anssi

2018-01-01

Two central dimensions in psychotherapeutic work are a therapist’s empathy with clients and challenging their judgments. We investigated how they influence psychophysiological responses in the participants. Data were from psychodynamic therapy sessions, 24 sessions from 5 dyads, from which 694 therapist’s interventions were coded. Heart rate and electrodermal activity (EDA) of the participants were used to index emotional arousal. Facial muscle activity (electromyography) was used to index positive and negative emotional facial expressions. Electrophysiological data were analyzed in two time frames: (a) during the therapists’ interventions and (b) across the whole psychotherapy session. Both empathy and challenge had an effect on psychophysiological responses in the participants. Therapists’ empathy decreased clients’ and increased their own EDA across the session. Therapists’ challenge increased their own EDA in response to the interventions, but not across the sessions. Clients, on the other hand, did not respond to challenges during interventions, but challenges tended to increase EDA across a session. Furthermore, there was an interaction effect between empathy and challenge. Heart rate decreased and positive facial expressions increased in sessions where empathy and challenge were coupled, i.e., the amount of both empathy and challenge was either high or low. This suggests that these two variables work together. The results highlight the therapeutic functions and interrelation of empathy and challenge, and in line with the dyadic system theory by Beebe and Lachmann (2002), the systemic linkage between interactional expression and individual regulation of emotion. PMID:29695992

Children's Expressions of Positive Emotion are Sustained by Smiling, Touching, and Playing with Parents and Siblings: A Naturalistic Observational Study of Family Life

PubMed Central

Bai, Sunhye; Repetti, Rena L.; Sperling, Jacqueline B.

2015-01-01

Research on family socialization of positive emotion has primarily focused on the infant and toddler stages of development, and relied on observations of parent-child interactions in highly structured laboratory environments. Little is known about how children's spontaneous expressions of positive emotion are maintained in the uncontrolled settings of daily life, particularly within the family and during the school-age years. This naturalistic observational study examines three family behaviors - mutual display of positive emotion, touch and joint leisure – that surround 8 to 12 year-old children's spontaneous expressions of positive emotion, and tests whether these behaviors help to sustain children's expressions. Recordings taken of 31 families in their homes and communities over two days were screened for moments when children spontaneously expressed positive emotion in the presence of at least one parent. Children were more likely to sustain their expressions of positive emotion when mothers, fathers or siblings showed positive emotion, touched, or participated in a leisure activity. There were few differences in the ways that mothers and fathers socialized their sons’ and daughters’ positive emotion expressions. This study takes a unique, ecologically valid approach to assess how family members connect to children's expressions of positive emotion in middle childhood. Future observational studies should continue to explore mechanisms of family socialization of positive emotion, in laboratory and naturalistic settings. PMID:26524382

Comparison of Breastfeeding Outcomes Between Using the Laid-Back and Side-Lying Breastfeeding Positions in Mothers Delivering by Cesarean Section: A Randomized Controlled Trial.

PubMed

Puapornpong, Pawin; Raungrongmorakot, Kasem; Laosooksathit, Wipada; Hanprasertpong, Tharangrut; Ketsuwan, Sukwadee

2017-05-01

The breastfeeding position routinely used following a cesarean section is the side-lying position. However, there have been few studies about the effect of breastfeeding positions, including laid-back position on breastfeeding outcomes. To compare the breastfeeding outcomes between using laid-back and side-lying breastfeeding positions in mothers delivering by cesarean section. A randomized controlled trial was conducted. The postpartum mothers delivering by cesarean section who delivered term newborns were randomly assigned to learn the use of a laid-back or side-lying breastfeeding position. The breastfeeding outcomes were assessed by LATCH scores at the second day postpartum and exclusive breastfeeding rates during the 6-week postpartum period. The mother's satisfaction of each breastfeeding position was collected before discharge from the hospital. The data from 152 postpartum mothers delivering by cesarean section were available for analysis, 76 from the laid-back position group and 76 from side-lying position group. The baseline characteristics of both groups were similar. There were no statistically significant differences of the breastfeeding outcomes, LATCH scores at the second day postpartum and the exclusive breastfeeding rates during the 6-week postpartum period. But the mothers had expressed more satisfaction from the side-lying than the laid-back position. Among the mothers who delivered by cesarean section, the use of the laid-back breastfeeding position had not shown different breastfeeding outcomes from the side-lying breastfeeding position. It might be an alternative breastfeeding position, which can be taught for mothers delivering by cesarean section along with the side-lying position.

An effect size filter improves the reproducibility in spectral counting-based comparative proteomics.

PubMed

Gregori, Josep; Villarreal, Laura; Sánchez, Alex; Baselga, José; Villanueva, Josep

2013-12-16

The microarray community has shown that the low reproducibility observed in gene expression-based biomarker discovery studies is partially due to relying solely on p-values to get the lists of differentially expressed genes. Their conclusions recommended complementing the p-value cutoff with the use of effect-size criteria. The aim of this work was to evaluate the influence of such an effect-size filter on spectral counting-based comparative proteomic analysis. The results proved that the filter increased the number of true positives and decreased the number of false positives and the false discovery rate of the dataset. These results were confirmed by simulation experiments where the effect size filter was used to evaluate systematically variable fractions of differentially expressed proteins. Our results suggest that relaxing the p-value cut-off followed by a post-test filter based on effect size and signal level thresholds can increase the reproducibility of statistical results obtained in comparative proteomic analysis. Based on our work, we recommend using a filter consisting of a minimum absolute log2 fold change of 0.8 and a minimum signal of 2-4 SpC on the most abundant condition for the general practice of comparative proteomics. The implementation of feature filtering approaches could improve proteomic biomarker discovery initiatives by increasing the reproducibility of the results obtained among independent laboratories and MS platforms. Quality control analysis of microarray-based gene expression studies pointed out that the low reproducibility observed in the lists of differentially expressed genes could be partially attributed to the fact that these lists are generated relying solely on p-values. Our study has established that the implementation of an effect size post-test filter improves the statistical results of spectral count-based quantitative proteomics. The results proved that the filter increased the number of true positives whereas decreased the false positives and the false discovery rate of the datasets. The results presented here prove that a post-test filter applying a reasonable effect size and signal level thresholds helps to increase the reproducibility of statistical results in comparative proteomic analysis. Furthermore, the implementation of feature filtering approaches could improve proteomic biomarker discovery initiatives by increasing the reproducibility of results obtained among independent laboratories and MS platforms. This article is part of a Special Issue entitled: Standardization and Quality Control in Proteomics. Copyright © 2013 Elsevier B.V. All rights reserved.

c-KIT positive schistosomal urinary bladder carcinoma are frequent but lack KIT gene mutations.

PubMed

Shams, Tahany M; Metawea, Mokhtar; Salim, Elsayed I

2013-01-01

Urinary bladder squamous cell carcinoma (SCC), one of the most common neoplasms in Egypt, is attributed to chronic urinary infection with Schistosoma haematobium (Schistosomiasis). The proto-oncogene c-KIT, encoding a tyrosine kinase receptor and implicated in the development of a number of human malignancies, has not been studied so far in schistosomal urinary bladder SCCs. We therefore determined immunohistochemical (IHC) expression of c-KIT in paraffin sections from 120 radical cystectomies of SCCs originally obtained from the Pathology Department of Suez Canal University (Ismailia, Egypt). Each slide was evaluated for staining intensity where the staining extent of >10% of cells was considered positive. c-KIT overexpression was detected in 78.3% (94/120) of the patients, the staining extents in the tumor cells were 11-50% and >50% in 40 (42.6%) and 54 (57.4%) respectively. The positive cases had 14.9%, 63.8%, 21.3% as weak, moderate and strong intensity respectively. Patients with positive bilharzial ova had significantly higher c-KIT expression than patients without (95.2% vs. 38.9%, P=0.000). Mutation analysis of exons 9-13 was negative in thirty KIT positive cases. The high rate of positivity in SBSCC was one of the striking findings; However, CD117 may be a potential target for site specific immunotherapy to improve the outcome of this tumor.

EGFR expression in circulating tumor cells from high-grade metastatic soft tissue sarcomas.

PubMed

Braun, Alexcia Camila; de Mello, Celso Abdon Lopes; Corassa, Marcelo; Abdallah, Emne Ali; Urvanegia, Ana Cláudia; Alves, Vanessa Silva; Flores, Bianca C T C P; Díaz, Mônica; Nicolau, Ulisses Ribaldo; Silva, Virgilio Souza E; Calsavara, Vinicius; Paterlini-Brechót, Patrizia; Chinen, Ludmilla Thomé Domingos

2018-06-03

Soft tissue Sarcomas (STS) are rare malignances, with high mortality rates. Half of patients develop metastasis. The presence of isolated Circulating Tumor Cells (CTCs) and Circulating Tumor Microemboli (CTM) in the blood may be early markers of tumor invasion. Epidermal Growth Factor (EGF) family receptors can also influence this process. to quantify CTCs and identify CTM as well as the EGF Receptor (EGFR) protein expression in these cells and correlate with clinical outcome in metastatic STS. Approximately 8mL of blood was prospectively collected from patients with different types of high-grade STS, before the beginning of chemotherapy. The samples were processed and filtered by ISET (Rarecells, France) for the isolation and quantification of CTCs and CTMs. EGFR expression was analyzed by immunocytochemistry (ICC) on CTCs/ CTMs. We analyzed 18 patients with median age of 49 years (18-77 y). The positivity for EGFR protein expression in CTCs was observed in 93.75% of the patients. This result shows that targeting EGFR positive CTCs from STS origen can be translated in clinical benefit for some patients. In addition, if target therapy is chosen, the EGFR expression in CTCs can be used in follow-up to measure treatment effectiveness. This is the first study to demonstrate the expression of EGFR protein in CTCs from sarcoma patients. It may open an area for future investigations. The next step is to characterize CTCs in a larger cohort of patients to better understand the role of EGFR in sustaining tumor metastasis in sarcomas.

Optimal Geometrical Set for Automated Marker Placement to Virtualized Real-Time Facial Emotions

PubMed Central

Maruthapillai, Vasanthan; Murugappan, Murugappan

2016-01-01

In recent years, real-time face recognition has been a major topic of interest in developing intelligent human-machine interaction systems. Over the past several decades, researchers have proposed different algorithms for facial expression recognition, but there has been little focus on detection in real-time scenarios. The present work proposes a new algorithmic method of automated marker placement used to classify six facial expressions: happiness, sadness, anger, fear, disgust, and surprise. Emotional facial expressions were captured using a webcam, while the proposed algorithm placed a set of eight virtual markers on each subject’s face. Facial feature extraction methods, including marker distance (distance between each marker to the center of the face) and change in marker distance (change in distance between the original and new marker positions), were used to extract three statistical features (mean, variance, and root mean square) from the real-time video sequence. The initial position of each marker was subjected to the optical flow algorithm for marker tracking with each emotional facial expression. Finally, the extracted statistical features were mapped into corresponding emotional facial expressions using two simple non-linear classifiers, K-nearest neighbor and probabilistic neural network. The results indicate that the proposed automated marker placement algorithm effectively placed eight virtual markers on each subject’s face and gave a maximum mean emotion classification rate of 96.94% using the probabilistic neural network. PMID:26859884

Evaluation of aldehyde dehydrogenase 1 and transcription factors in both primary breast cancer and axillary lymph node metastases as a prognostic factor.

PubMed

Ito, Maiko; Shien, Tadahiko; Omori, Masako; Mizoo, Taeko; Iwamoto, Takayuki; Nogami, Tomohiro; Motoki, Takayuki; Taira, Naruto; Doihara, Hiroyoshi; Miyoshi, Shinichiro

2016-05-01

Aldehyde dehydrogenase 1 (ALDH1) is a marker of breast cancer stem cells, and the expression of ALDH1 may be a prognostic factor of poor clinical outcome. The epithelial-mesenchymal transition may produce cells with stem-cell-like properties promoted by transcription factors. We investigated the expression of ALDH1 and transcription factors in both primary and metastatic lesions, and prognostic value of them in breast cancer patients with axillary lymph node metastasis (ALNM). Forty-seven breast cancer patients with ALNM who underwent surgery at Okayama University Hospital from 2002 to 2008 were enrolled. We retrospectively evaluated the levels of ALDH1 and transcription factors, such as Snail, Slug and Twist, in both primary and metastatic lesions by immunohistochemistry. In primary lesions, the positive rate of ALDH1, Snail, Slug and Twist was 19, 49, 40 and 26%, respectively. In lymph nodes, that of ALDH1, Snail, Slug and Twist was 21, 32, 13 and 23%, respectively. The expression of ALDH1 or transcription factors alone was not significantly associated with a poor prognosis. However, co-expression of ALDH1 and Slug in primary lesions was associated with a shorter DFS (P = 0.009). The evaluation of the co-expression of ALDH1 and transcription factors in primary lesions may be useful in prognosis of node-positive breast cancers.

Optimal Geometrical Set for Automated Marker Placement to Virtualized Real-Time Facial Emotions.

PubMed

Maruthapillai, Vasanthan; Murugappan, Murugappan

2016-01-01

In recent years, real-time face recognition has been a major topic of interest in developing intelligent human-machine interaction systems. Over the past several decades, researchers have proposed different algorithms for facial expression recognition, but there has been little focus on detection in real-time scenarios. The present work proposes a new algorithmic method of automated marker placement used to classify six facial expressions: happiness, sadness, anger, fear, disgust, and surprise. Emotional facial expressions were captured using a webcam, while the proposed algorithm placed a set of eight virtual markers on each subject's face. Facial feature extraction methods, including marker distance (distance between each marker to the center of the face) and change in marker distance (change in distance between the original and new marker positions), were used to extract three statistical features (mean, variance, and root mean square) from the real-time video sequence. The initial position of each marker was subjected to the optical flow algorithm for marker tracking with each emotional facial expression. Finally, the extracted statistical features were mapped into corresponding emotional facial expressions using two simple non-linear classifiers, K-nearest neighbor and probabilistic neural network. The results indicate that the proposed automated marker placement algorithm effectively placed eight virtual markers on each subject's face and gave a maximum mean emotion classification rate of 96.94% using the probabilistic neural network.

TmCactin plays an important role in Gram-negative and -positive bacterial infection by regulating expression of 7 AMP genes in Tenebrio molitor

PubMed Central

Jo, Yong Hun; Jung Kim, Yu; Beom Park, Ki; Hwan Seong, Jeong; Gon Kim, Soo; Park, Soyi; Young Noh, Mi; Seok Lee, Yong; Soo Han, Yeon

2017-01-01

Cactin was originally identified as an interactor of the Drosophila IκB factor Cactus and shown to play a role in controlling embryonic polarity and regulating the NF-κB signaling pathway. While subsequent studies have identified the roles for Cactin in the mammalian immune response, the immune function of Cactin in insects has not been described yet. Here, we identified a Cactin gene from the mealworm beetle, Tenebrio molitor (TmCactin) and characterized its functional role in innate immunity. TmCactin was highly expressed in prepupa to last instar stages, and its expression was high in the integument and Malpighian tubules of last instar larvae and adults. TmCactin was induced in larvae after infection with different pathogens and detectable within 3 hours of infection. The highest levels of TmCactin expression were detected at 9 hours post infection. TmCactin RNAi significantly decreased the survival rates of larvae after challenge with Escherichia coli and Staphylococcus aureus, but had no significant effect after challenge with Candida albicans. Furthermore, TmCactin RNAi significantly reduced the expression of seven antimicrobial peptide genes (AMPs) after bacterial challenge. Our results suggest that TmCactin may serve as an important regulator of innate immunity, mediating AMP responses against both Gram-positive and Gram-negative bacteria in T. molitor. PMID:28418029

Positive Selection Linked with Generation of Novel Mammalian Dentition Patterns.

PubMed

Machado, João Paulo; Philip, Siby; Maldonado, Emanuel; O'Brien, Stephen J; Johnson, Warren E; Antunes, Agostinho

2016-09-11

A diverse group of genes are involved in the tooth development of mammals. Several studies, focused mainly on mice and rats, have provided a detailed depiction of the processes coordinating tooth formation and shape. Here we surveyed 236 tooth-associated genes in 39 mammalian genomes and tested for signatures of selection to assess patterns of molecular adaptation in genes regulating mammalian dentition. Of the 236 genes, 31 (∼13.1%) showed strong signatures of positive selection that may be responsible for the phenotypic diversity observed in mammalian dentition. Mammalian-specific tooth-associated genes had accelerated mutation rates compared with older genes found across all vertebrates. More recently evolved genes had fewer interactions (either genetic or physical), were associated with fewer Gene Ontology terms and had faster evolutionary rates compared with older genes. The introns of these positively selected genes also exhibited accelerated evolutionary rates, which may reflect additional adaptive pressure in the intronic regions that are associated with regulatory processes that influence tooth-gene networks. The positively selected genes were mainly involved in processes like mineralization and structural organization of tooth specific tissues such as enamel and dentin. Of the 236 analyzed genes, 12 mammalian-specific genes (younger genes) provided insights on diversification of mammalian teeth as they have higher evolutionary rates and exhibit different expression profiles compared with older genes. Our results suggest that the evolution and development of mammalian dentition occurred in part through positive selection acting on genes that previously had other functions. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Accelerated Evolution of Developmentally Biased Genes in the Tetraphenic Ant Cardiocondyla obscurior.

PubMed

Schrader, Lukas; Helanterä, Heikki; Oettler, Jan

2017-03-01

Plastic gene expression underlies phenotypic plasticity and plastically expressed genes evolve under different selection regimes compared with ubiquitously expressed genes. Social insects are well-suited models to elucidate the evolutionary dynamics of plastic genes for their genetically and environmentally induced discrete polymorphisms. Here, we study the evolution of plastically expressed genes in the ant Cardiocondyla obscurior-a species that produces two discrete male morphs in addition to the typical female polymorphism of workers and queens. Based on individual-level gene expression data from 28 early third instar larvae, we test whether the same evolutionary dynamics that pertain to plastically expressed genes in adults also pertain to genes with plastic expression during development. In order to quantify plasticity of gene expression over multiple contrasts, we develop a novel geometric measure. For genes expressed during development, we show that plasticity of expression is positively correlated with evolutionary rates. We furthermore find a strong correlation between expression plasticity and expression variation within morphs, suggesting a close link between active and passive plasticity of gene expression. Our results support the notion of relaxed selection and neutral processes as important drivers in the evolution of adaptive plasticity. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Targeting mTOR and AREG with everolimus, sunitinib and sorafenib in HPV-positive and -negative SCC.

PubMed

Aderhold, Christoph; Faber, Anne; Umbreit, Claudia; Birk, Richard; Weiss, Christel; Sommer, Jörg Ulrich; Hörmann, Karl; Schultz, Johannes David

2015-04-01

Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial malignancy. It is the most common neoplasm appearing in the upper aerodigestive tract and the sixth most common cancer worldwide. The five-year survival rate remains poor despite advances in surgery, radiation and chemotherapy. Furthermore, the incidence of human papillomavirus (HPV)-associated oropharyngeal cancer is rising. Thus, innovative therapy approaches are imperative in order to improve the situation. Everolimus, an inhibitor of the mammalian target of rapamycin (mTOR) and sorafenib and sunitinib, multityrosine kinase inhibitors, have been notably effective in the therapy of different tumor entities. The modest side-effects and oral application of the drugs might improve patient compliance. Expression levels of mTOR and Amphiregulin (AREG) in p16-positive and -negative SCC (squamous cell carcinoma) and the effect of everolimus, sorafenib or sunitinib on the expression levels of these target proteins were assessed. As far as we are aware of, this is one of the first in vitro studies to evaluate the effect of these small-molecule drugs with regard to the p16 status of SCC cells. p16-negative HNSCC 11A and 14C cells and p16-positive CERV196 cells were exposed to different concentrations of everolimus, sorafenib and sunitinib for 2-8 days. Expression levels of mTOR and AREG were determined by enzyme-linked immunosorbent assay (ELISA) and compared against a chemonaïve control. AREG and mTOR were expressed in all tested cell lines. CERV196 displayed a remarkable increase of mTOR expression compared to p16-negative HNSCC. On the contrary, AREG levels were reduced by 50% in CERV196. Everolimus, sorafenib and sunitinib significantly reduced mTOR expression. Everolimus significantly decreased AREG expression independently of the HPV status. Sunitinib and sorafenib increased AREG expression in HNSCC 11A and 14C but not in CERV196. The applied drugs showed remarkable suppression of mTOR expression, which might delay tumor progression. Interestingly, sorafenib and sunitinib increased AREG in HNSCC 11A and 14C, which could be a possible evasive mechanism following incubation with these drugs. On the contrary, p16-positive CERV196 showed increased susceptibility to sorafenib and sunitinib concerning suppression of AREG expression. Further studies are required to evaluate the HPV-dependent differences of therapy response and the possible consequences for treatment options. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Pose-variant facial expression recognition using an embedded image system

NASA Astrophysics Data System (ADS)

Song, Kai-Tai; Han, Meng-Ju; Chang, Shuo-Hung

2008-12-01

In recent years, one of the most attractive research areas in human-robot interaction is automated facial expression recognition. Through recognizing the facial expression, a pet robot can interact with human in a more natural manner. In this study, we focus on the facial pose-variant problem. A novel method is proposed in this paper to recognize pose-variant facial expressions. After locating the face position in an image frame, the active appearance model (AAM) is applied to track facial features. Fourteen feature points are extracted to represent the variation of facial expressions. The distance between feature points are defined as the feature values. These feature values are sent to a support vector machine (SVM) for facial expression determination. The pose-variant facial expression is classified into happiness, neutral, sadness, surprise or anger. Furthermore, in order to evaluate the performance for practical applications, this study also built a low resolution database (160x120 pixels) using a CMOS image sensor. Experimental results show that the recognition rate is 84% with the self-built database.

Immunohistochemical evaluation of inducible nitric oxide synthase in the epithelial lining of odontogenic cysts: A qualitative and quantitative analysis.

PubMed

Akshatha, B K; Karuppiah, Karpagaselvi; Manjunath, G S; Kumarswamy, Jayalakshmi; Papaiah, Lokesh; Rao, Jyothi

2017-01-01

The three common odontogenic cysts include radicular cysts (RCs), dentigerous cysts (DCs), and odontogenic keratocysts (OKCs). Among these 3 cysts, OKC is recently been classified as benign keratocystic odontogenic tumor attributing to its aggressive behavior, recurrence rate, and malignant potential. The present study involved qualitative and quantitative analysis of inducible nitric oxide synthase (iNOS) expression in epithelial lining of RCs, DCs, and OKCs, compare iNOS expression in epithelial linings of all the 3 cysts and determined overexpression of iNOS in OKCs which might contribute to its aggressive behavior and malignant potential. The present study is to investigate the role of iNOS in the pathogenesis of OKCs, DCs, and RCs by evaluating the iNOS expression in the epithelial lining of these cysts. Analysis of iNOS expression in epithelial lining cells of 20 RCs, 20 DCs, and 20 OKCs using immunohistochemistry done. The percentage of positive cells and intensity of stain was assessed and compared among all the 3 cysts using contingency coefficient. Kappa statistics for the two observers were computed for finding interobserver agreement. The percentage of iNOS-positive cells was found to be remarkably high in OKCs (12/20) -57.1% as compared to RCs (6/20) - 28.6% and DCs (3/20) - 14.3%. The interobserver agreement for iNOS-positive percentage cells was arrived with kappa values with OKCs → Statistically significant ( P > 0.000), RCs → statistically significant ( P > 0.001) with no significant values for DCs. No statistical difference exists among 3 study samples in regard to the intensity of staining with iNOS. Increased iNOS expression in OKCs may contribute to bone resorption and accumulation of wild-type p53, hence, making OKCs more aggressive.

Correlation between molecular analysis, diagnosis according to the 2015 WHO classification of unresected lung tumours and TTF1 expression in small biopsies and cytology specimens from 344 non-small cell lung carcinoma patients.

PubMed

Russell, Prudence A; Rogers, Toni-Maree; Solomon, Benjamin; Alam, Naveed; Barnett, Stephen A; Rathi, Vivek; Williams, Richard A; Wright, Gavin M; Conron, Matthew

2017-10-01

We investigated correlations between diagnosis according to the 2015 World Health Organization (WHO) classification of unresected lung tumours, molecular analysis and TTF1 expression in small biopsy and cytology specimens from 344 non-small cell lung carcinoma (NSCLC) patients. One case failed testing for EGFR, KRAS and ALK abnormalities and six had insufficient tumour for ALK testing. Overall mutation rate in 343 cases was 48% for the genes tested, with 19% EGFR, 33% KRAS and 4% BRAF mutations, and 5% ALK rearrangements detected. More EGFR-mutant (78%) and ALK-rearranged (75%) tumours had morphologic adenocarcinoma than KRAS-mutant (56%) tumours. Despite no significant difference in the overall rate of any molecular abnormality between morphologic adenocarcinoma (52%) and NSCLC, favour adenocarcinoma (47%) (p = 0.18), KRAS mutations were detected more frequently in the latter group. No significant difference in the overall rate of any molecular abnormality between TTF1 positive (49%) and TTF1 negative tumours (44%) (p = 0.92) was detected, but more EGFR-mutant (97%) and ALK-rearranged tumours (92%) were TTF1 positive than KRAS-mutant tumours (68%). Rates of EGFR, KRAS and BRAF mutations and ALK rearrangements in this Australian NSCLC patient population are consistent with the published international literature. Our findings suggest that 2015 WHO classification of unresected tumours may assist in identifying molecular subsets of advanced NSCLC. Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Sensing emotion in voices: Negativity bias and gender differences in a validation study of the Oxford Vocal ('OxVoc') sounds database.

PubMed

Young, Katherine S; Parsons, Christine E; LeBeau, Richard T; Tabak, Benjamin A; Sewart, Amy R; Stein, Alan; Kringelbach, Morten L; Craske, Michelle G

2017-08-01

Emotional expressions are an essential element of human interactions. Recent work has increasingly recognized that emotional vocalizations can color and shape interactions between individuals. Here we present data on the psychometric properties of a recently developed database of authentic nonlinguistic emotional vocalizations from human adults and infants (the Oxford Vocal 'OxVoc' Sounds Database; Parsons, Young, Craske, Stein, & Kringelbach, 2014). In a large sample (n = 562), we demonstrate that adults can reliably categorize these sounds (as 'positive,' 'negative,' or 'sounds with no emotion'), and rate valence in these sounds consistently over time. In an extended sample (n = 945, including the initial n = 562), we also investigated a number of individual difference factors in relation to valence ratings of these vocalizations. Results demonstrated small but significant effects of (a) symptoms of depression and anxiety with more negative ratings of adult neutral vocalizations (R2 = .011 and R2 = .008, respectively) and (b) gender differences in perceived valence such that female listeners rated adult neutral vocalizations more positively and infant cry vocalizations more negatively than male listeners (R2 = .021, R2 = .010, respectively). Of note, we did not find evidence of negativity bias among other affective vocalizations or gender differences in perceived valence of adult laughter, adult cries, infant laughter, or infant neutral vocalizations. Together, these findings largely converge with factors previously shown to impact processing of emotional facial expressions, suggesting a modality-independent impact of depression, anxiety, and listener gender, particularly among vocalizations with more ambiguous valence. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

MALAT1-miR-124-RBG2 axis is involved in growth and invasion of HR-HPV-positive cervical cancer cells.

PubMed

Liu, Shikai; Song, Lili; Zeng, Saitian; Zhang, Liang

2016-01-01

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT 1) is a large, infrequently spliced non-coding RNA aberrantly expressed in cervical cancer. But the molecular mechanisms of its oncogenic role are still not quite clear. The present study explored whether there is a competing endogenous RNAs (ceRNAs) mechanism involved in the oncogenic effect of MALAT1. MALAT1 expression was firstly verified in high-risk human papillomavirus (HR-HPV)-positive tumor tissues and cell lines. Its regulation over miR-124 and the downstream target of miR-124 in regulation of growth, invasion, and apoptosis of the cancer cells are also studied. Findings of this study confirmed higher MALAT1 expression in HR-HPV (+) cervical cancer. Knockdown of endogenous MALAT1 significantly reduced cell growth rate and invasion and increased cell apoptosis of Hela and siHa cells. Besides, knockdown of MALAT1 increased the expression of miRNA-124, while ectopic expression of miR-124 decreased MALAT1 expression. In addition, we also verified a direct interaction between miR-124 and 3'UTR of GRB2. MALAT1 can indirectly modulate GRB2 expression via competing miR-124. Knockdown of GRB2 reduced cell invasion and increased cell apoptosis. In conclusion, MALAT1 can promote HR-HPV (+) cancer cell growth and invasion at least partially through the MALAT1-miR-124-RBG2 axis. This finding might provide some useful evidence about the lncRNA interaction regulatory network in tumorigenesis cervical cancer.

Maternal Personality: Longitudinal Associations to Parenting Behavior and Maternal Emotional Expressions toward Toddlers

PubMed Central

Smith, Cynthia L.; Spinrad, Tracy L.; Eisenberg, Nancy; Gaertner, Bridget M.; Popp, Tierney K.; Maxon, Elizabeth

2007-01-01

SYNOPSIS Objective Longitudinal associations among maternal personality, emotional expressions, and parenting were examined. Design Maternal parenting (sensitivity and intrusiveness) and positive emotional expressions were observed during a free-play session with toddlers at 18 (T1, n = 246) and 30 (T3, n = 216) months. Mothers completed a personality measure at T1 and a questionnaire measuring their emotional expressiveness (positive and negative) when toddlers were 24 months old (T2, n = 213). Results Dimensions of maternal personality and maternal emotional expressiveness were related to individual differences in maternal parenting behaviors, in particular to maternal sensitivity. Conscientiousness and Agreeableness at T1 were positively associated with observed positive emotional expressions at T1. Agreeableness, Openness to Experience, and Extraversion at T1 also were positively related to positive emotional expressions reported by mothers at T2. Maternal positive emotional expressions (T1 and T2), in turn, were associated with more sensitive behavior observed with toddlers at T3. Conclusion In addition to direct effects of maternal personality on maternal parenting, mothers’ emotional expressiveness was found to be a possible pathway for explaining relations of maternal personality and parenting. PMID:18174914

Expressive Behavior in Parkinson's Disease as a Function of Interview Context

PubMed Central

Takahashi, Kayoko; Tickle-Degnen, Linda; Coster, Wendy J.; Latham, Nancy K.

2010-01-01

OBJECTIVE Parkinson's disease affects the ability to express motivation through face, body, and voice; contextual factors may facilitate or inhibit expressive behavior. The purpose of this study was to determine whether qualities of the interview context are associated with client motivational behavior in Parkinson's disease. METHOD Men and women with Parkinson's disease (N = 106) discussed 2 topics (enjoyable activity vs. frustrating activity) during an assessment with a female or male interviewer. From videotaped clips, displays of 4 categories of motivation and 12 verbal and 18 nonverbal behavioral patterns were rated. RESULTS During the discussion of enjoyable activities, participants used more positive words, smiled more, and were more facially expressive. Participants were less talkative about their negative feelings and appeared to be more apathetic with the same-gender interviewer. CONCLUSION Occupational therapy practitioners should vary the emotional tone of their questions to improve the validity of motivation assessments. PMID:20608279

[Expression and significance of immunosuppressive acidic protein (IAP) in human esophageal squamous cell carcinoma].

PubMed

Guo, S Z; Shen, Q; Zhang, H B

1994-03-01

The expression of IAP in the esophageal tissues of 74 patients with esophageal squamous cell carcinoma and 12 normal controls were determined by using MI2, and anti-IAP monoclonal antibody, and ABC immunohistochemical staining. The results showed that there was no expression of IAP in normal esophageal epithelium of all control subjects, and the positive rate in specimens of the esophageal carcinomas was 90.3% (P < 0.001). The staining intensity of IAP was increasing with the decrease in degrees of cell differentiation of the tumors (P < 0.05). The expression of IAP in long survivors without lymph node metastasis were lower than that in cases with metastasis (P < 0.005) and short survivors (P < 0.001). The results suggest that IAP may play an important role in tumor cell differentiation, clinical course and prognosis of esophageal carcinoma, and may be used as a tumor marker for the diagnosis of this malignancy.

Economic evaluation of genomic test-directed chemotherapy for early-stage lymph node-positive breast cancer.

PubMed

Hall, Peter S; McCabe, Christopher; Stein, Robert C; Cameron, David

2012-01-04

Multi-parameter genomic tests identify patients with early-stage breast cancer who are likely to derive little benefit from adjuvant chemotherapy. These tests can potentially spare patients the morbidity from unnecessary chemotherapy and reduce costs. However, the costs of the test must be balanced against the health benefits and cost savings produced. This economic evaluation compared genomic test-directed chemotherapy using the Oncotype DX 21-gene assay with chemotherapy for all eligible patients with lymph node-positive, estrogen receptor-positive early-stage breast cancer. We performed a cost-utility analysis using a state transition model to calculate expected costs and benefits over the lifetime of a cohort of women with estrogen receptor-positive lymph node-positive breast cancer from a UK perspective. Recurrence rates for Oncotype DX-selected risk groups were derived from parametric survival models fitted to data from the Southwest Oncology Group 8814 trial. The primary outcome was the incremental cost-effectiveness ratio, expressed as the cost (in 2011 GBP) per quality-adjusted life-year (QALY). Confidence in the incremental cost-effectiveness ratio was expressed as a probability of cost-effectiveness and was calculated using Monte Carlo simulation. Model parameters were varied deterministically and probabilistically in sensitivity analysis. Value of information analysis was used to rank priorities for further research. The incremental cost-effectiveness ratio for Oncotype DX-directed chemotherapy using a recurrence score cutoff of 18 was £5529 (US $8852) per QALY. The probability that test-directed chemotherapy is cost-effective was 0.61 at a willingness-to-pay threshold of £30 000 per QALY. Results were sensitive to the recurrence rate, long-term anthracycline-related cardiac toxicity, quality of life, test cost, and the time horizon. The highest priority for further research identified by value of information analysis is the recurrence rate in test-selected subgroups. There is substantial uncertainty regarding the cost-effectiveness of Oncotype DX-directed chemotherapy. It is particularly important that future research studies to inform cost-effectiveness-based decisions collect long-term outcome data.

Quantitative proteomic analysis reveals a simple strategy of global resource allocation in bacteria

PubMed Central

Hui, Sheng; Silverman, Josh M; Chen, Stephen S; Erickson, David W; Basan, Markus; Wang, Jilong; Hwa, Terence; Williamson, James R

2015-01-01

A central aim of cell biology was to understand the strategy of gene expression in response to the environment. Here, we study gene expression response to metabolic challenges in exponentially growing Escherichia coli using mass spectrometry. Despite enormous complexity in the details of the underlying regulatory network, we find that the proteome partitions into several coarse-grained sectors, with each sector's total mass abundance exhibiting positive or negative linear relations with the growth rate. The growth rate-dependent components of the proteome fractions comprise about half of the proteome by mass, and their mutual dependencies can be characterized by a simple flux model involving only two effective parameters. The success and apparent generality of this model arises from tight coordination between proteome partition and metabolism, suggesting a principle for resource allocation in proteome economy of the cell. This strategy of global gene regulation should serve as a basis for future studies on gene expression and constructing synthetic biological circuits. Coarse graining may be an effective approach to derive predictive phenomenological models for other ‘omics’ studies. PMID:25678603

Prediction of Fetal Growth Restriction by Analyzing the Messenger RNAs of Angiogenic Factor in the Plasma of Pregnant Women.

PubMed

Takenaka, Shin; Ventura, Walter; Sterrantino, Anna Freni; Kawashima, Akihiro; Koide, Keiko; Hori, Kyoko; Farina, Antonio; Sekizawa, Akihiko

2015-06-01

To predict the occurrence of fetal growth restriction (FGR) by analyzing messenger RNA (mRNA) expression levels of vascular endothelial growth factor receptor 1 (fms-like tyrosine kinase 1 [Flt-1]) in maternal blood. Eleven women with FGR were matched with 88 controls. Plasma samples were obtained during each trimester. The Flt-1 mRNA expression levels were compared between groups. Predicted probabilities were calculated, and sensitivity-specificity (receiver-operating characteristic [ROC]) curves were assessed based on regression models for each trimester measurement and possible combinations of measurements. The mRNA levels of the FGR group during all trimesters were significantly higher than those of the control group. The ROC curve of combined first and second trimester data yielded a detection rate of 60% at a 10% false-positive rate, with an area under curve of 0.79. The Flt-1 mRNA expression in maternal blood can be used as a marker to predict the development of FGR, long before a clinical diagnosis is made. © The Author(s) 2014.

Wnt1 from cochlear schwann cells enhances neuronal differentiation of transplanted neural stem cells in a rat spiral ganglion neuron degeneration model.

PubMed

He, Ya; Zhang, Peng-Zhi; Sun, Dong; Mi, Wen-Juan; Zhang, Xin-Yi; Cui, Yong; Jiang, Xing-Wang; Mao, Xiao-Bo; Qiu, Jian-Hua

2014-04-01

Although neural stem cell (NSC) transplantation is widely expected to become a therapy for nervous system degenerative diseases and injuries, the low neuronal differentiation rate of NSCs transplanted into the inner ear is a major obstacle for the successful treatment of spiral ganglion neuron (SGN) degeneration. In this study, we validated whether the local microenvironment influences the neuronal differentiation of transplanted NSCs in the inner ear. Using a rat SGN degeneration model, we demonstrated that transplanted NSCs were more likely to differentiate into microtubule-associated protein 2 (MAP2)-positive neurons in SGN-degenerated cochleae than in control cochleae. Using real-time quantitative PCR and an immunofluorescence assay, we also proved that the expression of Wnt1 (a ligand of Wnt signaling) increases significantly in Schwann cells in the SGN-degenerated cochlea. We further verified that NSC cultures express receptors and signaling components for Wnts. Based on these expression patterns, we hypothesized that Schwann cell-derived Wnt1 and Wnt signaling might be involved in the regulation of the neuronal differentiation of transplanted NSCs. We verified our hypothesis in vitro using a coculture system. We transduced a lentiviral vector expressing Wnt1 into cochlear Schwann cell cultures and cocultured them with NSC cultures. The coculture with Wnt1-expressing Schwann cells resulted in a significant increase in the percentage of NSCs that differentiated into MAP2-positive neurons, whereas this differentiation-enhancing effect was prevented by Dkk1 (an inhibitor of the Wnt signaling pathway). These results suggested that Wnt1 derived from cochlear Schwann cells enhanced the neuronal differentiation of transplanted NSCs through Wnt signaling pathway activation. Alterations of the microenvironment deserve detailed investigation because they may help us to conceive effective strategies to overcome the barrier of the low differentiation rate of transplanted NSCs.

The growth-inhibitory and apoptosis-inducing effect of deferoxamine combined with arsenic trioxide on HL-60 xenografts in nude mice.

PubMed

Yu, Runhong; Wang, Dao; Ren, Xiuhua; Zeng, Li; Liu, Yufeng

2014-09-01

The aim of this study is to investigate the growth-inhibitory and apoptosis-inducing effect of deferoxamine (DFO) combined with arsenic trioxide (ATO) on the human HL-60 xenografts in nude mice and its mechanism. The highly tumorigenic leukemia cell line HL-60 cells were inoculated subcutaneously into nude mice to establish a human leukemia xenograft model. The HL-60 xenograft nude mice models were randomly divided into four groups: control (Normal saline, NS), 50mg/kg DFO, 3mg/kg ATO, the combined treatment (50mg/kg DFO+1.5mg/kg ATO) once HL-60 cells were inoculated. Tumor sizes, growth curves, inhibitory rates, cell apoptosis, and the expression of apoptosis related markers were measured to evaluate the tumor growth. Xenografted tumors were observed in all nude mice since the 5th day of inoculation. The inhibitory rates of tumor weight were 2.67%, 10.69%, and 25.57% in DFO, ATO and combination therapy groups, respectively. The combination of DFO with ATO induces significantly more tumor cell apoptosis than either agent alone (p<0.05). The expression of NF-κBp65 and survivin proteins decreased significantly while the expression of Caspase-3 and Bax increased in the combination therapy group (p<0.05). Double immunofluorescence for Caspase-3 and NFκBp65 demonstrated an inverse relationship between Caspase-3-positive areas and NFκBp65-positive areas, as well as the co-localization of Bax and survivin in xenografted tumor cells. Combination of DFO and ATO has synergistic effects on tumor growth inhibition and apoptosis-inducing in vivo with no significant side effects. The DFO and ATO can up-regulate the expression of Caspase-3 and Bax, and down-regulate the expression of NF-κBp65 and survivin, especially for their combination. Copyright © 2014 Elsevier Ltd. All rights reserved.

Context matters: the benefits and costs of expressing positive emotion among survivors of childhood sexual abuse.

PubMed

Bonanno, George A; Colak, Deniz M; Keltner, Dacher; Shiota, Michelle N; Papa, Anthony; Noll, Jennie G; Putnam, Frank W; Trickett, Penelope K

2007-11-01

Positive emotions promote adjustment to aversive life events. However, evolutionary theory and empirical research on trauma disclosure suggest that in the context of stigmatized events, expressing positive emotions might incur social costs. To test this thesis, the authors coded genuine (Duchenne) smiling and laughter and also non-Duchenne smiling from videotapes of late-adolescent and young adult women, approximately half with documented histories of childhood sexual abuse (CSA), as they described the most distressing event of their lives. Consistent with previous studies, genuine positive emotional expression was generally associated with better social adjustment two years later. However, as anticipated, CSA survivors who expressed positive emotion in the context of describing a past CSA experience had poorer long-term social adjustment, whereas CSA survivors who expressed positive emotion while describing a nonabuse experience had improved social adjustment. These findings suggest that the benefits of positive emotional expression may often be context specific.

Expression of BMP-4 in papillary thyroid carcinoma and its correlation with tumor invasion and progression.

PubMed

Meng, Xiaomei; Zhu, Peng; Li, Ning; Hu, Jinchen; Wang, Shaoguang; Pang, Shuguang; Wang, Jiahui

2017-04-01

Bone morphogenetic protein 4 (BMP-4) is a member of the BMP protein family. BMP-4 was reported to induce epithelial-mesenchymal transition (EMT) and promote tumor cell immigration and invasion. This study aimed to investigate the expression of BMP-4 in papillary thyroid carcinoma (PTC) and its correlation with the patients' clinicophathological features and with tumor invasion and metastasis. Surgically resected PTC specimens from 82 patients admitted to the Department of Thyroid Surgery of Yantai Yuhuangding Hospital between Feb 1st and May 31st, 2016 were collected. The expression level of BMP-4 in PTC tissues was examined by immunohistochemical staining. The full clinical records of all patients were collected to analyze the relevance between BMP-4 expression and the clinical pathological features of PTC. Our result showed that BMP-4-positive cell rate and staining intensity were positively correlated with the patient's age (P=0.031, 0.037), tumor size (P=0.033, 0.019), capsular invasion (P=0.001, 0.002) and TNM stage (P=0.001, 0.004), while not correlated with gender, multicentricity of tumor or lymphatic metastasis. In conclusion, this study identified BMP-4 as a potential molecular marker for predicting the invasion and progression of PTC. Copyright © 2017 Elsevier GmbH. All rights reserved.

Prognostic value of platelet-derived growth factor-A (PDGF-A) in gastric carcinoma.

PubMed Central

Katano, M; Nakamura, M; Fujimoto, K; Miyazaki, K; Morisaki, T

1998-01-01

OBJECTIVE: Because our previous study indicated that PDGF-A mRNA expression in biopsy specimens might identify a subgroup of high-risk patients with gastric carcinoma, in this study we analyzed the prognostic value of platelet-derived growth factor-A (PDGF-A) gene expression in gastric carcinoma biopsy specimens. METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to analyze the PDGF-A gene expression in 65 gastric carcinoma endoscopic biopsy specimens. The 65 patients were divided into a PDGF-A-positive group (29 patients) and a PDGF-A-negative group (36 patients). RESULTS: On the basis of 2-year follow-up data, the PDGF-A-positive group demonstrated a shorter overall survival rate compared with the PDGF-A-negative group (p < 0.0001). A similar correlation was found in 34 advanced-stage patients (p = 0.003) and in 24 advanced-stage patients who underwent a curative resection (p = 0.003). Multivariance analysis indicated that the transcription of PDGF-A gene is a potent prognostic factor that is independent of the traditional pathologic parameters. CONCLUSIONS: Expression of PDGF-A mRNA in gastric biopsy specimens may be a new preoperative prognostic parameter in gastric carcinoma. Images Figure 1. Figure 5. PMID:9527059

Dual-Pulse Pulse Position Modulation (DPPM) for Deep-Space Optical Communications: Performance and Practicality Analysis

NASA Technical Reports Server (NTRS)

Li, Jing; Hylton, Alan; Budinger, James; Nappier, Jennifer; Downey, Joseph; Raible, Daniel

2012-01-01

Due to its simplicity and robustness against wavefront distortion, pulse position modulation (PPM) with photon counting detector has been seriously considered for long-haul optical wireless systems. This paper evaluates the dual-pulse case and compares it with the conventional single-pulse case. Analytical expressions for symbol error rate and bit error rate are first derived and numerically evaluated, for the strong, negative-exponential turbulent atmosphere; and bandwidth efficiency and throughput are subsequently assessed. It is shown that, under a set of practical constraints including pulse width and pulse repetition frequency (PRF), dual-pulse PPM enables a better channel utilization and hence a higher throughput than it single-pulse counterpart. This result is new and different from the previous idealistic studies that showed multi-pulse PPM provided no essential information-theoretic gains than single-pulse PPM.

[Effect of ultraviolet radiation on ALDH1 expression in human lens epithelial cells].

PubMed

Shi, Jingming; Jia, Songbai; Chen, Xuan; Tang, Luosheng

2012-06-01

To determine the apoptosis-inducing effect of ultraviolet light (UV) on human lens epithelial cell (HLEC) and to explore the involvement of changes in ALDH1 folowing UV radiation. HLEC was exposed to the same UV light source and was subsequently divided into 6 groups according to UV radiation time of 0 (control group), 5, 10, 15, and 30 min. Apoptosis was detected by AO/EB staining. Changes of ALDH1 in HLEC were detected by immunohistochemical staining and Western blot. The intensity of immunohistochemical staining and the rate of positive cells decreased with increase of UV time (P<0.05). The rate of positive ALDH1 cells was negatively correlated with the rate of apoptosis (r= -0.92, P<0.05). Western blot showed the integrated absorbance values significantly decreased with the increase of UV time (P<0.05). ALDH1 in HLEC decreases with an increase of UV exposure, which may be related to UV induced apoptosis of HLEC.

Effect of diabetes mellitus on the quality and cytokine content of human semen.

PubMed

Lu, Xiaosheng; Huang, Yonggang; Zhang, Huina; Zhao, Junzhao

2017-09-01

The effects of diabetes mellitus (DM) on the quality and cytokine levels of human semen remain unknown. Sixty semen samples from 30 normal volunteers and 30 DM patients were assayed. The percentage of sperm progressive motility, sperm vitality, sperm survival rate, the rate of normal sperm morphology, semen volume, and semen pH and density of DM males were significantly lower than those of normal males (p<0.05). Moreover, semen interleukin (IL)-17 and IL-18 levels in DM males were significantly higher than those in normal males (p<0.05) and were positively correlated with blood glucose level and sperm DNA fragmentation index. DM increased blood glucose levels, consequently inducing the abnormal expression of IL-17 and IL-18. The abnormal expression of these cytokines in semen decreased semen quality and might lead to male infertility. Copyright © 2017 Elsevier B.V. All rights reserved.

Analysis of cagA in Helicobacter pylori strains from Colombian populations with contrasting gastric cancer risk reveals a biomarker for disease severity

PubMed Central

Loh, John T.; Shaffer, Carrie L.; Piazuelo, M. Blanca; Bravo, Luis E.; McClain, Mark S.; Correa, Pelayo; Cover, Timothy L.

2011-01-01

BACKGROUND Helicobacter pylori infection is a risk factor for the development of gastric cancer, and the bacterial oncoprotein CagA contributes to gastric carcinogenesis. METHODS We analyzed H. pylori isolates from persons in Colombia and observed that there was marked variation among strains in levels of CagA expression. To elucidate the basis for this variation, we analyzed sequences upstream from the CagA translational initiation site in each strain. RESULTS A DNA motif (AATAAGATA) upstream of the translational initiation site of CagA was associated with high levels of CagA expression. Experimental studies showed that this motif was necessary but not sufficient for high-level CagA expression. H. pylori strains from a region of Colombia with high gastric cancer rates expressed higher levels of CagA than did strains from a region with lower gastric cancer rates, and Colombian strains of European phylogeographic origin expressed higher levels of CagA than did strains of African origin. Histopathological analysis of gastric biopsy specimens revealed that strains expressing high levels of CagA or containing the AATAAGATA motif were associated with more advanced precancerous lesions than those found in persons infected with strains expressing low levels of CagA or lacking the AATAAGATA motif. CONCLUSIONS CagA expression varies greatly among H. pylori strains. The DNA motif identified in this study is associated with high levels of CagA expression, and may be a useful biomarker to predict gastric cancer risk. IMPACT These findings help to explain why some persons infected with cagA-positive H. pylori develop gastric cancer and others do not. PMID:21859954

HTLV-1 Integration into Transcriptionally Active Genomic Regions Is Associated with Proviral Expression and with HAM/TSP

PubMed Central

Meekings, Kiran N.; Leipzig, Jeremy; Bushman, Frederic D.; Taylor, Graham P.; Bangham, Charles R. M.

2008-01-01

Human T-lymphotropic virus type 1 (HTLV-1) causes leukaemia or chronic inflammatory disease in ∼5% of infected hosts. The level of proviral expression of HTLV-1 differs significantly among infected people, even at the same proviral load (proportion of infected mononuclear cells in the circulation). A high level of expression of the HTLV-1 provirus is associated with a high proviral load and a high risk of the inflammatory disease of the central nervous system known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). But the factors that control the rate of HTLV-1 proviral expression remain unknown. Here we show that proviral integration sites of HTLV-1 in vivo are not randomly distributed within the human genome but are associated with transcriptionally active regions. Comparison of proviral integration sites between individuals with high and low levels of proviral expression, and between provirus-expressing and provirus non-expressing cells from within an individual, demonstrated that frequent integration into transcription units was associated with an increased rate of proviral expression. An increased frequency of integration sites in transcription units in individuals with high proviral expression was also associated with the inflammatory disease HAM/TSP. By comparing the distribution of integration sites in human lymphocytes infected in short-term cell culture with those from persistent infection in vivo, we infer the action of two selective forces that shape the distribution of integration sites in vivo: positive selection for cells containing proviral integration sites in transcriptionally active regions of the genome, and negative selection against cells with proviral integration sites within transcription units. PMID:18369476

ENHANCED BETA-CATENIN EXPRESSION IS ASSOCIATED WITH THE RECURRENCE OF PAPILLARY THYROID CARCINOMA.

PubMed

Kordestani, Zeinab; Sanjari, Mojgan; Safavi, Moeinadin; Mashrouteh, Mahdieh; Asadikaram, Gholamreza; FekriSoofiAbadi, Maryam; Mirzazadeh, Ali

2018-03-02

A direct role of Catenin beta-1(βcat) in the proliferation of human thyroid tumor cells has been identified. This study aimed to determine if there is an association between βcat gene expression and the staging, recurrence, metastasis, and disease free survival of papillary thyroid cancer. A retrospective cohort study was conducted using data from available information in the medical records and paraffin blocks of 81 of 400 patients referred to the endocrine clinic over a 10-year period. Real-time polymerase chain reaction (PCR) was used to evaluate βcat gene expression. Disease-free survival was assessed using Kaplan-Meier method. The ten-year survival rate in these patients was 98.25% and disease-free survival was 48.1%. Cumulative dose of radioactive iodine that patients received was significantly and positively correlated with βcat gene expression (r = -0.2, p value=0.03).Also, in patients with recurrence, βcat gene expression was higher and statistically significant (5 fold increase p=0.002). Patients in more advanced stage and those with recurrence /distant metastasis had higher βcat gene expression .We found that the patients had a better survival (lower recurrence) if they had a lower βcat gene expression. (SD = 0.142-0.052) (Mantel-Cox test, P =0.002). We concluded that βcat gene expression was positively correlated with recurrence, distant metastasis and TNM stage. PTC = Papillary thyroid carcinoma; βcat = Catenin beta-1; FTC = Follicular thyroid cancer; TCF/LEF-1 = T-cell factor / lymphoid enhancer factor1; IHC = immunohistochemical; TG = Thyroglobulin; AUC = Area under the ROC curve; APC = Adenomatosis polyposis coli.

Cloning and expression of the translocator protein (18 kDa), voltage-dependent anion channel, and diazepam binding inhibitor in the gonad of largemouth bass (Micropterus salmoides) across the reproductive cycle.

PubMed

Doperalski, Nicholas J; Martyniuk, Christopher J; Prucha, Melinda S; Kroll, Kevin J; Denslow, Nancy D; Barber, David S

2011-08-01

Cholesterol transport across the mitochondrial membrane is rate-limiting for steroidogenesis in vertebrates. Previous studies in fish have characterized expression of the steroidogenic acute regulatory protein, however the function and regulation of other genes and proteins involved in piscine cholesterol transport have not been evaluated. In the current study, mRNA sequences of the 18 kDa translocator protein (tspo; formerly peripheral benzodiazepine receptor), voltage-dependent anion channel (vdac), and diazepam binding inhibitor (dbi; also acyl-CoA binding protein) were cloned from largemouth bass. Gonadal expression was examined across reproductive stages to determine if expression is correlated with changes in steroid levels and with indicators of reproductive maturation. In testis, transcript abundance of tspo and dbi increased with reproductive maturation (6- and 23-fold maximal increase, respectively) and expression of tspo and dbi was positively correlated with reproductive stage, gonadosomatic index (GSI), and circulating levels of testosterone. Testis vdac expression was positively correlated with reproductive stage and GSI. In females, gonadal tspo and vdac expression was negatively correlated with GSI and levels of plasma testosterone and 17β-estradiol. Ovarian dbi expression was not correlated with indicators of reproductive maturation. These studies represent the first investigation of the steroidogenic role of tspo, vdac, and dbi in fish. Findings suggest that cholesterol transport in largemouth bass testis, but not in ovary, may be transcriptionally-regulated, however further investigation will be necessary to fully elucidate the role of these genes in largemouth bass steroidogenesis. Copyright © 2011 Elsevier Inc. All rights reserved.

An optimized ERP brain-computer interface based on facial expression changes.

PubMed

Jin, Jing; Daly, Ian; Zhang, Yu; Wang, Xingyu; Cichocki, Andrzej

2014-06-01

Interferences from spatially adjacent non-target stimuli are known to evoke event-related potentials (ERPs) during non-target flashes and, therefore, lead to false positives. This phenomenon was commonly seen in visual attention-based brain-computer interfaces (BCIs) using conspicuous stimuli and is known to adversely affect the performance of BCI systems. Although users try to focus on the target stimulus, they cannot help but be affected by conspicuous changes of the stimuli (such as flashes or presenting images) which were adjacent to the target stimulus. Furthermore, subjects have reported that conspicuous stimuli made them tired and annoyed. In view of this, the aim of this study was to reduce adjacent interference, annoyance and fatigue using a new stimulus presentation pattern based upon facial expression changes. Our goal was not to design a new pattern which could evoke larger ERPs than the face pattern, but to design a new pattern which could reduce adjacent interference, annoyance and fatigue, and evoke ERPs as good as those observed during the face pattern. Positive facial expressions could be changed to negative facial expressions by minor changes to the original facial image. Although the changes are minor, the contrast is big enough to evoke strong ERPs. In this paper, a facial expression change pattern between positive and negative facial expressions was used to attempt to minimize interference effects. This was compared against two different conditions, a shuffled pattern containing the same shapes and colours as the facial expression change pattern, but without the semantic content associated with a change in expression, and a face versus no face pattern. Comparisons were made in terms of classification accuracy and information transfer rate as well as user supplied subjective measures. The results showed that interferences from adjacent stimuli, annoyance and the fatigue experienced by the subjects could be reduced significantly (p < 0.05) by using the facial expression change patterns in comparison with the face pattern. The offline results show that the classification accuracy of the facial expression change pattern was significantly better than that of the shuffled pattern (p < 0.05) and the face pattern (p < 0.05). The facial expression change pattern presented in this paper reduced interference from adjacent stimuli and decreased the fatigue and annoyance experienced by BCI users significantly (p < 0.05) compared to the face pattern.

An optimized ERP brain-computer interface based on facial expression changes

NASA Astrophysics Data System (ADS)

Jin, Jing; Daly, Ian; Zhang, Yu; Wang, Xingyu; Cichocki, Andrzej

2014-06-01

Objective. Interferences from spatially adjacent non-target stimuli are known to evoke event-related potentials (ERPs) during non-target flashes and, therefore, lead to false positives. This phenomenon was commonly seen in visual attention-based brain-computer interfaces (BCIs) using conspicuous stimuli and is known to adversely affect the performance of BCI systems. Although users try to focus on the target stimulus, they cannot help but be affected by conspicuous changes of the stimuli (such as flashes or presenting images) which were adjacent to the target stimulus. Furthermore, subjects have reported that conspicuous stimuli made them tired and annoyed. In view of this, the aim of this study was to reduce adjacent interference, annoyance and fatigue using a new stimulus presentation pattern based upon facial expression changes. Our goal was not to design a new pattern which could evoke larger ERPs than the face pattern, but to design a new pattern which could reduce adjacent interference, annoyance and fatigue, and evoke ERPs as good as those observed during the face pattern. Approach. Positive facial expressions could be changed to negative facial expressions by minor changes to the original facial image. Although the changes are minor, the contrast is big enough to evoke strong ERPs. In this paper, a facial expression change pattern between positive and negative facial expressions was used to attempt to minimize interference effects. This was compared against two different conditions, a shuffled pattern containing the same shapes and colours as the facial expression change pattern, but without the semantic content associated with a change in expression, and a face versus no face pattern. Comparisons were made in terms of classification accuracy and information transfer rate as well as user supplied subjective measures. Main results. The results showed that interferences from adjacent stimuli, annoyance and the fatigue experienced by the subjects could be reduced significantly (p < 0.05) by using the facial expression change patterns in comparison with the face pattern. The offline results show that the classification accuracy of the facial expression change pattern was significantly better than that of the shuffled pattern (p < 0.05) and the face pattern (p < 0.05). Significance. The facial expression change pattern presented in this paper reduced interference from adjacent stimuli and decreased the fatigue and annoyance experienced by BCI users significantly (p < 0.05) compared to the face pattern.

Sex-specific hormone receptors in urothelial carcinomas of the human urinary bladder: a comparative analysis of clinicopathological features and survival outcomes according to receptor expression.

PubMed

Tuygun, Can; Kankaya, Duygu; Imamoglu, Abdurrahim; Sertcelik, Ayse; Zengin, Kursad; Oktay, Murat; Sertcelik, Nurettin

2011-01-01

To investigate the expression of sex-specific hormone receptors in normal bladder urothelium and urothelial carcinomas (UCs) of the bladder, and to analyze clinicopathological features and survival outcomes according to receptor expression. We evaluated the clinical data and tumor specimens of 139 patients with bladder cancer (BC). In addition, 72 samples of normal urothelium were included. Immunohistochemistry was performed using streptavidin-biotin peroxidase method, a monoclonal androgen receptor (AR), and an estrogen receptor-β (ERβ) antibody on paraffin-embedded tissue sections. Expression levels of each receptor were assessed by evaluating 500 tumor cells for each case and the percentage of positively-stained nuclei was recorded. None of the 58 male control cases showed any AR and ERβ expression. Five (35, 71%) of the 14 female control cases expressed ERβ. Of the 139 patients with UCs, 71 (51, 07%) expressed AR (62 male vs. 9 female; P = 0.413) and 44 (31, 65%) (39 male vs. 5 female; P = 0.402) showed ERβ expression (P < 0.001). No significant relationship was found between ERβ expression levels and tumor grades, and stages (P = 0.441; P = 0.247). AR expression was significantly lower in T2-tumors (21%) than in Ta-tumors (60%) and T1-tumors (60%) (P < 0.001). It was significantly higher in low-grade papillary UCs (64%) compared with high-grade papillary UCs (44%) and infiltrative high-grade UCs (17%) (P = 0.039; P < 0.001). Data of 79 patients with noninvasive BC were eligible to present, with a median 29 months follow-up. AR expression level did not influence recurrence-free survival (RFS) and progression-free survival (PFS) (P = 0.095; P = 0.110). No significant association was found between ERβ expression level and RFS (P = 0.293). PFS in patients with lower ERβ-expressing tumors was significantly better than that in patients with higher ERβ-expressing tumors (P = 0.035). Multivariate analysis confirmed this significant influence on PFS (P = 0.025). Although ERβ expression had no impact on histopathological tumor characteristics, decrease in its expression may be associated with better PFS rates in patients with noninvasive BC. Conversely, loss of AR expression was associated with higher grade UCs and invasive UCs, but had no prognostic effect on survival. Finally, sex-specific hormone receptors alone cannot be responsible for gender differences in BC rates because they were expressed in similar rates in both sexes. Copyright © 2011 Elsevier Inc. All rights reserved.

Impaired hippocampal rate coding after lesions of the lateral entorhinal cortex.

PubMed

Lu, Li; Leutgeb, Jill K; Tsao, Albert; Henriksen, Espen J; Leutgeb, Stefan; Barnes, Carol A; Witter, Menno P; Moser, May-Britt; Moser, Edvard I

2013-08-01

In the hippocampus, spatial and non-spatial parameters may be represented by a dual coding scheme, in which coordinates in space are expressed by the collective firing locations of place cells and the diversity of experience at these locations is encoded by orthogonal variations in firing rates. Although the spatial signal may reflect input from medial entorhinal cortex, the sources of the variations in firing rate have not been identified. We found that rate variations in rat CA3 place cells depended on inputs from the lateral entorhinal cortex (LEC). Hippocampal rate remapping, induced by changing the shape or the color configuration of the environment, was impaired by lesions in those parts of the ipsilateral LEC that provided the densest input to the hippocampal recording position. Rate remapping was not observed in LEC itself. The findings suggest that LEC inputs are important for efficient rate coding in the hippocampus.

Multiple Transcript Properties Related to Translation Affect mRNA Degradation Rates in Saccharomyces cerevisiae

PubMed Central

Neymotin, Benjamin; Ettorre, Victoria; Gresham, David

2016-01-01

Degradation of mRNA contributes to variation in transcript abundance. Studies of individual mRNAs have shown that both cis and trans factors affect mRNA degradation rates. However, the factors underlying transcriptome-wide variation in mRNA degradation rates are poorly understood. We investigated the contribution of different transcript properties to transcriptome-wide degradation rate variation in the budding yeast, Saccharomyces cerevisiae, using multiple regression analysis. We find that multiple transcript properties are significantly associated with variation in mRNA degradation rates, and that a model incorporating these properties explains ∼50% of the genome-wide variance. Predictors of mRNA degradation rates include transcript length, ribosome density, biased codon usage, and GC content of the third position in codons. To experimentally validate these factors, we studied individual transcripts expressed from identical promoters. We find that decreasing ribosome density by mutating the first translational start site of a transcript increases its degradation rate. Using coding sequence variants of green fluorescent protein (GFP) that differ only at synonymous sites, we show that increased GC content of the third position of codons results in decreased rates of mRNA degradation. Thus, in steady-state conditions, a large fraction of genome-wide variation in mRNA degradation rates is determined by inherent properties of transcripts, many of which are related to translation, rather than specific regulatory mechanisms. PMID:27633789

The relationship between the expression of TAM, survivin and the degree of necrosis of the tumor after cisplatin treatment in osteosarcoma.

PubMed

Chen, G

2017-02-01

To explore the relationship between the expression of TAM, survivin and the degree of necrosis of the tumor after cisplatin treatment in osteosarcoma. The mice model of osteosarcoma S180 were injected with 6 mg/kg/day of cisplatin (observation group) or the same amount of normal saline (control group) for 4 weeks. Mice were sacrificed at days 1, 4, 9, 14, 18, 22 and 28, respectively, 24 h before administration of the drug or saline, and tumor tissues were collected. The size of the tumor samples was measured and the correlation of TAM, survivin expression in osteosarcoma and necrosis degree of tumor tissue after cisplatin treatment was studied using various methods including fluorescence quantitative PCR, enzyme linked immunosorbent assay (ELISA), Western blotting and immunohistochemistry. Fluorescence quantitative PCR showed that the expression of TAM, survivin mRNA in the control group was significantly higher than that in the observation group. Also, the ELISA monitoring showed that the expression of mice TAM, survivin protein in vivo was significantly lower than TAM, survivin protein expression of mice in vivo in the observation group (2.3 µg/l, 1.6 µg/l) relatively to the control group (9.7 mg/l, 10.3 µg/l). Consistent with the Western blot data, ELISA results showed that the expression of survivin and TAM protein decreased gradually with the prolongation of drug treatment along the time in the observation group. The volume and weight of the tumor in the observation group were significantly less than that of the control group. Additionally, the tumor necrosis of mice in the observation group was more significant, suggesting that the meant of the size of tumor tissue decreased significantly with the extension of the time of drug treatment. Immunohistochemical results showed that the rate of the positive cell of TAM and survivin in the observation group (82.3%) was significantly higher (p<0.05) than that in the control group (19.5%). However, the rate of the positive cell of survivin and TAM gradually declined at the level of the trend with the extension of the time of drug treatment in the observation group. Cisplatin treatment can inhibit the expression of TAM and survivin in osteosarcoma tissue sand then, promote the necrosis of tumor tissue.

Expression and prognostic examination of heat shock proteins (HSP 27, HSP 70, and HSP 90) in medulloblastoma.

PubMed

Hauser, Péter; Hanzély, Zoltán; Jakab, Zsuzsanna; Oláh, Lászlóné; Szabó, Erika; Jeney, András; Schuler, Dezso; Fekete, Gyoörgy; Bognár, László; Garami, Miklós

2006-07-01

Expression of heat shock proteins (HSPs) is of prognostic significance in several tumor types. HSP expression levels were determined in medulloblastomas and tested whether HSPs expression was associated with prognostic parameters. Expression of antiapoptotic HSP 27, HSP 70, and HSP 90 was investigated by immunohistochemistry, on paraffin-embedded sections from 65 patients. Expression of HSPs was validated on internal vascular controls and by Western blotting analysis. Sample evaluation was based on the estimated percentage of HSP positive tumor cells. For survival analysis Kaplan-Meier method, for statistical analysis chi2 test, univariate analysis, and log rank test were applied. Expression of HSPs varied in medulloblastomas. On the basis of the average expression rate of HSPs, at HSP 27 and HSP 90 with a 10% cut off, and at HSP 70 with a 70% cut off 2 groups were created. The amount of expression of any of the HSP types was not significantly associated with known prognostic factors (age of patient, extent of resection, presence of metastasis) and histologic subtype. After an average follow-up period of 4.30 years, no significant difference was observed in survival depending on the expression of HSP 27 or HSP 70 or HSP 90. The high expression of HSPs indicates that these proteins are potential therapeutic targets.

Correlation analysis between expression of PCNA, Ki-67 and COX-2 and X-ray features in mammography in breast cancer.

PubMed

Qiu, Xiaoming; Mei, Jixin; Yin, Jianjun; Wang, Hong; Wang, Jinqi; Xie, Ming

2017-09-01

This study investigated expression of proliferating cell nuclear antigen (PCNA), proliferation-associated nuclear antigen (Ki-67) and cyclooxygenase-2 (COX-2) in tissues of breast invasive ductal carcinoma, and analyzed the correlations between these indexes and X-ray features in mammography. A total of 90 patients who were admitted to Huangshi Central Hospital and diagnosed as breast invasive ductal carcinoma from January 2014 to January 2016 were selected. The expression of PCNA, Ki-67 and COX-2 in cancer tissues and cancer-adjacent normal tissues of patients were detected by immunohistochemical staining, and X-ray features in mammography of patients were observed. By using Spearman correlation analysis, the correlations between expression of PCNA, Ki-67 and COX-2 and X-ray features in mammography in breast cancer were investigated. As a result, the positive expression rates of PCNA, Ki-67 and COX-2 in cancer tissues of the patient groups were respectively 42.2, 45.6 and 51.1%, which were significantly higher than those in cancer-adjacent normal tissues of the control group (p<0.05). PCNA, Ki-67 and COX-2 expression in cancer tissues of the patient group was associated with clinical staging and lymphatic metastasis (p<0.05), but had no correlation with age and tumor size (p>0.05). PCNA, Ki-67 and COX-2 expression in cancer tissues of the patient group had no correlation with the existence of lumps and localized density-increased shadows (p>0.05), but were associated with manifestations of architectural distortion, calcification as well as skin and nipple depression (p<0.05). Spearman correlation analysis revealed that there was a significantly positive correlation between the expression of PCNA and COX-2 in cancer tissues of the patient group (r=0.676, p<0.05); there was a significantly positive correlation between the expression of Ki-67 and COX-2 (r=0.724, p<0.05); PCNA expression had no obvious correlation with the expression of Ki-67 (p>0.05). In conclusion, PCNA, Ki-67 and COX-2 expression is of great significance in the occurrence, invasion and metastasis of breast invasive ductal carcinoma. There is a strong correlation between PCNA, Ki-67 and COX-2 expression levels and X-ray features in mammography in breast invasive ductal carcinoma. The application of X-ray features in mammography can evaluate the expression levels of PCNA, Ki-67 and COX-2 in tissues of breast invasive ductal carcinoma, thereby prospectively predicting biological behavior of these cancer cells and patient prognosis.

Radotinib induces high cytotoxicity in c-KIT positive acute myeloid leukemia cells.

PubMed

Heo, Sook-Kyoung; Noh, Eui-Kyu; Kim, Jeong Yi; Jo, Jae-Cheol; Choi, Yunsuk; Koh, SuJin; Baek, Jin Ho; Min, Young Joo; Kim, Hawk

2017-06-05

Previously, we reported that radotinib, a BCR-ABL1 tyrosine kinase inhibitor, induced cytotoxicity in acute myeloid leukemia (AML) cells. However, the effects of radotinib in the subpopulation of c-KIT-positive AML cells were unclear. We observed that low-concentration radotinib had more potent cytotoxicity in c-KIT-positive cells than c-KIT-negative cells from AML patients. To address this issue, cell lines with high c-KIT expression, HEL92.1.7, and moderate c-KIT expression, H209, were selected. HEL92.1.7 cells were grouped into intermediate and high c-KIT expression populations. The cytotoxicity of radotinib against the HEL92.1.7 cell population with intermediate c-KIT expression was not different from that of the population with high c-KIT expression. When H209 cells were grouped into c-KIT expression-negative and c-KIT expression-positive populations, radotinib induced cytotoxicity in the c-KIT-positive population, but not the c-KIT-negative population. Thus, radotinib induces cytotoxicity in c-KIT-positive cells, regardless of the c-KIT expression intensity. Therefore, radotinib induces significant cytotoxicity in c-KIT-positive AML cells, suggesting that radotinib is a potential target agent for the treatment of c-KIT-positive malignancies including AML. Copyright © 2017 Elsevier B.V. All rights reserved.

Pinpointing retrovirus entry sites in cells expressing alternatively spliced receptor isoforms by single virus imaging.

PubMed

Padilla-Parra, Sergi; Marin, Mariana; Kondo, Naoyuki; Melikyan, Gregory B

2014-06-16

The majority of viruses enter host cells via endocytosis. Current knowledge of viral entry pathways is largely based upon infectivity measurements following genetic and/or pharmacological interventions that disrupt vesicular trafficking and maturation. Imaging of single virus entry in living cells provides a powerful means to delineate viral trafficking pathways and entry sites under physiological conditions. Here, we visualized single avian retrovirus co-trafficking with markers for early (Rab5) and late (Rab7) endosomes, acidification of endosomal lumen and the resulting viral fusion measured by the viral content release into the cytoplasm. Virus-carrying vesicles either merged with the existing Rab5-positive early endosomes or slowly accumulated Rab5. The Rab5 recruitment to virus-carrying endosomes correlated with acidification of their lumen. Viral fusion occurred either in early (Rab5-positive) or intermediate (Rab5- and Rab7-positive) compartments. Interestingly, different isoforms of the cognate receptor directed virus entry from distinct endosomes. In cells expressing the transmembrane receptor, viruses preferentially entered and fused with slowly maturing early endosomes prior to accumulation of Rab7. By comparison, in cells expressing the GPI-anchored receptor, viruses entered both slowly and quickly maturing endosomes and fused with early (Rab5-positive) and intermediate (Rab5- and Rab7-positive) compartments. Since the rate of low pH-triggered fusion was independent of the receptor isoform, we concluded that the sites of virus entry are determined by the kinetic competition between endosome maturation and viral fusion. Our findings demonstrate the ability of this retrovirus to enter cells via alternative endocytic pathways and establish infection by releasing its content from distinct endosomal compartments.

High-sensitivity human papilloma virus genotyping reveals near universal positivity in anal squamous cell carcinoma: different implications for vaccine prevention and prognosis.

PubMed

Baricevic, Ivona; He, Xiaotong; Chakrabarty, Bipasha; Oliver, Anthony W; Bailey, Charles; Summers, Jeff; Hampson, Lynne; Hampson, Ian; Gilbert, Duncan C; Renehan, Andrew G

2015-04-01

Characterisation of human papilloma virus (HPV) infection in anal squamous cell carcinoma (ASCC) may have dual importance: first, aetiological; second, prognostic, informing outcome after chemo-radiotherapy (CRT). We undertook HPV genotyping, and allelic characterisations, to evaluate the aetiological role of HPV while simultaneously evaluating the impact of HPV genotyping on relapse-free (RFS) and overall survival (OS). Dual-primer HPV genotyping (subtypes 6, 11, 16, 18, 31, 33, 45, 52, 58) and DNA sequencing of HPV 16 positive tumours were analysed in 151 consecutively referred ASCCs, previously characterised by immunohistochemistry for p16 expression. In 110 patients treated with CRT, factors influencing RFS and OS were evaluated using univariate and multivariate models. HPV positivity was observed in 95%. HPV 16 accounted for 89%; of these, 64% harboured the T350G E6 variant. HPV 16 positivity was significantly correlated with improved 5-year RFS (62% versus 40%; p = 0.027) and OS (59% versus 38%; p = 0.019). p16 expression was also significantly correlated with improved 5-year RFS (positive versus negative: 65% versus 16%; p < 0.0001) and OS (63% versus 13%; p < 0.0001). In multivariable models that included HPV 16 status, p16 status, sex, and age, p16 expression remained an independent prognostic factor for RFS (p < 0.0001) and OS (p = 0.002). In ASCC, near-universal HPV detection rates were demonstrated, higher than generally reported in the literature, and supporting the development of multivalent HPV vaccinations for prevention. By contrast, p16 negatively, but not HPV 16 genotype, is an independent adverse prognosticator after chemo-radiotherapy in patients with ASCC. Copyright © 2015. Published by Elsevier Ltd.

Demand theory of gene regulation. II. Quantitative application to the lactose and maltose operons of Escherichia coli.

PubMed Central

Savageau, M A

1998-01-01

Induction of gene expression can be accomplished either by removing a restraining element (negative mode of control) or by providing a stimulatory element (positive mode of control). According to the demand theory of gene regulation, which was first presented in qualitative form in the 1970s, the negative mode will be selected for the control of a gene whose function is in low demand in the organism's natural environment, whereas the positive mode will be selected for the control of a gene whose function is in high demand. This theory has now been further developed in a quantitative form that reveals the importance of two key parameters: cycle time C, which is the average time for a gene to complete an ON/OFF cycle, and demand D, which is the fraction of the cycle time that the gene is ON. Here we estimate nominal values for the relevant mutation rates and growth rates and apply the quantitative demand theory to the lactose and maltose operons of Escherichia coli. The results define regions of the C vs. D plot within which selection for the wild-type regulatory mechanisms is realizable, and these in turn provide the first estimates for the minimum and maximum values of demand that are required for selection of the positive and negative modes of gene control found in these systems. The ratio of mutation rate to selection coefficient is the most relevant determinant of the realizable region for selection, and the most influential parameter is the selection coefficient that reflects the reduction in growth rate when there is superfluous expression of a gene. The quantitative theory predicts the rate and extent of selection for each mode of control. It also predicts three critical values for the cycle time. The predicted maximum value for the cycle time C is consistent with the lifetime of the host. The predicted minimum value for C is consistent with the time for transit through the intestinal tract without colonization. Finally, the theory predicts an optimum value of C that is in agreement with the observed frequency for E. coli colonizing the human intestinal tract. PMID:9691028

Evolution of major histocompatibility complex class I and class II genes in the brown bear

PubMed Central

2012-01-01

Background Major histocompatibility complex (MHC) proteins constitute an essential component of the vertebrate immune response, and are coded by the most polymorphic of the vertebrate genes. Here, we investigated sequence variation and evolution of MHC class I and class II DRB, DQA and DQB genes in the brown bear Ursus arctos to characterise the level of polymorphism, estimate the strength of positive selection acting on them, and assess the extent of gene orthology and trans-species polymorphism in Ursidae. Results We found 37 MHC class I, 16 MHC class II DRB, four DQB and two DQA alleles. We confirmed the expression of several loci: three MHC class I, two DRB, two DQB and one DQA. MHC class I also contained two clusters of non-expressed sequences. MHC class I and DRB allele frequencies differed between northern and southern populations of the Scandinavian brown bear. The rate of nonsynonymous substitutions (dN) exceeded the rate of synonymous substitutions (dS) at putative antigen binding sites of DRB and DQB loci and, marginally significantly, at MHC class I loci. Models of codon evolution supported positive selection at DRB and MHC class I loci. Both MHC class I and MHC class II sequences showed orthology to gene clusters found in the giant panda Ailuropoda melanoleuca. Conclusions Historical positive selection has acted on MHC class I, class II DRB and DQB, but not on the DQA locus. The signal of historical positive selection on the DRB locus was particularly strong, which may be a general feature of caniforms. The presence of MHC class I pseudogenes may indicate faster gene turnover in this class through the birth-and-death process. South–north population structure at MHC loci probably reflects origin of the populations from separate glacial refugia. PMID:23031405

Evolution of major histocompatibility complex class I and class II genes in the brown bear.

PubMed

Kuduk, Katarzyna; Babik, Wiesław; Bojarska, Katarzyna; Sliwińska, Ewa B; Kindberg, Jonas; Taberlet, Pierre; Swenson, Jon E; Radwan, Jacek

2012-10-02

Major histocompatibility complex (MHC) proteins constitute an essential component of the vertebrate immune response, and are coded by the most polymorphic of the vertebrate genes. Here, we investigated sequence variation and evolution of MHC class I and class II DRB, DQA and DQB genes in the brown bear Ursus arctos to characterise the level of polymorphism, estimate the strength of positive selection acting on them, and assess the extent of gene orthology and trans-species polymorphism in Ursidae. We found 37 MHC class I, 16 MHC class II DRB, four DQB and two DQA alleles. We confirmed the expression of several loci: three MHC class I, two DRB, two DQB and one DQA. MHC class I also contained two clusters of non-expressed sequences. MHC class I and DRB allele frequencies differed between northern and southern populations of the Scandinavian brown bear. The rate of nonsynonymous substitutions (dN) exceeded the rate of synonymous substitutions (dS) at putative antigen binding sites of DRB and DQB loci and, marginally significantly, at MHC class I loci. Models of codon evolution supported positive selection at DRB and MHC class I loci. Both MHC class I and MHC class II sequences showed orthology to gene clusters found in the giant panda Ailuropoda melanoleuca. Historical positive selection has acted on MHC class I, class II DRB and DQB, but not on the DQA locus. The signal of historical positive selection on the DRB locus was particularly strong, which may be a general feature of caniforms. The presence of MHC class I pseudogenes may indicate faster gene turnover in this class through the birth-and-death process. South-north population structure at MHC loci probably reflects origin of the populations from separate glacial refugia.

AID protein expression in chronic lymphocytic leukemia/small lymphocytic lymphoma is associated with poor prognosis and complex genetic alterations.

PubMed

Leuenberger, Mona; Frigerio, Simona; Wild, Peter J; Noetzli, Franziska; Korol, Dimitri; Zimmermann, Dieter R; Gengler, Carole; Probst-Hensch, Nicole M; Moch, Holger; Tinguely, Marianne

2010-02-01

The biological behavior of chronic lymphocytic leukemia and small lymphocytic lymphoma is unpredictable. Nonetheless, non-mutated IgV(H) gene rearrangement, ATM (11q22-23) and p53 (17p13) deletion are recognized as unfavorable prognosticators in chronic lymphocytic leukemia. The mRNA expression of activation-induced cytidine deaminase (AID), an enzyme indispensable for somatic hypermutation processes, was claimed to be predictive of non-mutated chronic lymphocytic leukemia cells in blood. Here, we evaluated AID protein expression compared with known molecular and immunohistochemical prognostic indicators in 71 chronic lymphocytic leukemia/small lymphocytic lymphoma patients using a tissue microarray approach. We found AID heterogeneously expressed in tumor cells as shown by colocalization analysis for CD5 and CD23. Ki-67 positive paraimmunoblasts of the proliferation centers displayed the highest expression. This observation is reflected by a significant association of AID positivity with a high proliferation rate (P=0.012). ATM deletion was detected in 10% (6/63) of patients and p53 deletion in 19% (13/67) of patients. Moreover, both ATM (P=0.002) and p53 deletion (P=0.004) were significantly associated with AID. IgV(H) gene mutation was seen in 45% (27/60) of patients. Twenty-five percent (17/69) of patients with AID-positive chronic lymphocytic leukemia/small lymphocytic lymphoma displayed a shorter survival than AID-negative chronic lymphocytic leukemia/small lymphocytic lymphoma patients (61 vs 130 months, P=0.001). Although there was a trend, we could not show an association with the IgV(H) gene mutation status. Taken together, our study shows that AID expression is an indicator of an unfavorable prognosis in chronic lymphocytic leukemia/small lymphocytic lymphoma patients, although it is not a surrogate marker for the IgV(H) status. Furthermore, the microenvironment of proliferation centers seems to influence AID regulation and might be an initiating factor in its transformation.

Measurement of serum antibodies against NY-ESO-1 by ELISA: A guide for the treatment of specific immunotherapy for patients with advanced colorectal cancer.

PubMed

Long, Yan-Yan; Wang, Yu; Huang, Qian-Rong; Zheng, Guang-Shun; Jiao, Shun-Chang

2014-10-01

NY-ESO-1 has been identified as one of the most immunogenic antigens; thus, is a highly attractive target for cancer immunotherapy. The present study analyzed the expression of serum antibodies (Abs) against NY-ESO-1 in patients with advanced colorectal cancer (CRC), with the aim of guiding the treatment of NY-ESO-1-based specific-immunotherapy for these patients. Furthermore, the present study was the first to evaluate the kinetic expression of anti-NY-ESO-1 Abs and investigate the possible influencing factors. A total of 239 serum samples from 155 pathologically confirmed patients with advanced CRC (stages III and IV) were collected. The presence of spontaneous Abs against NY-ESO-1 was analyzed using an enzyme-linked immunosorbent assay (ELISA). The results demonstrated that 24.5% (38/155) of the investigated patients were positive for NY-ESO-1-specific Abs. No statistically significant correlations were identified between the expression of anti-NY-ESO-1 Abs and clinicopathological parameters, including age and gender, location, grading, local infiltration, lymph node status, metastatic status and K-ras mutation status (P>0.05). In 59 patients, the kinetic expression of anti-NY-ESO-1 Abs was analyzed, of which 14 patients were initially positive and 45 patients were initially negative. Notably, 16/59 (27.1%) patients changed their expression status during the study period, and the initially positive patients were more likely to change compared with the initially negative patients (85.7 vs. 8.8%; P<0.001). Therefore, monitoring serum Abs against NY-ESO-1 by ELISA is an easy and feasible method. The high expression rate of NY-ESO-1-specific Abs in CRC patients indicates that measuring the levels of serum Abs against NY-ESO-1 may guide the treatment of NY-ESO-1-based specific immunotherapy for patients with advanced CRC.

Measurement of serum antibodies against NY-ESO-1 by ELISA: A guide for the treatment of specific immunotherapy for patients with advanced colorectal cancer

PubMed Central

LONG, YAN-YAN; WANG, YU; HUANG, QIAN-RONG; ZHENG, GUANG-SHUN; JIAO, SHUN-CHANG

2014-01-01

NY-ESO-1 has been identified as one of the most immunogenic antigens; thus, is a highly attractive target for cancer immunotherapy. The present study analyzed the expression of serum antibodies (Abs) against NY-ESO-1 in patients with advanced colorectal cancer (CRC), with the aim of guiding the treatment of NY-ESO-1-based specific-immunotherapy for these patients. Furthermore, the present study was the first to evaluate the kinetic expression of anti-NY-ESO-1 Abs and investigate the possible influencing factors. A total of 239 serum samples from 155 pathologically confirmed patients with advanced CRC (stages III and IV) were collected. The presence of spontaneous Abs against NY-ESO-1 was analyzed using an enzyme-linked immunosorbent assay (ELISA). The results demonstrated that 24.5% (38/155) of the investigated patients were positive for NY-ESO-1-specific Abs. No statistically significant correlations were identified between the expression of anti-NY-ESO-1 Abs and clinicopathological parameters, including age and gender, location, grading, local infiltration, lymph node status, metastatic status and K-ras mutation status (P>0.05). In 59 patients, the kinetic expression of anti-NY-ESO-1 Abs was analyzed, of which 14 patients were initially positive and 45 patients were initially negative. Notably, 16/59 (27.1%) patients changed their expression status during the study period, and the initially positive patients were more likely to change compared with the initially negative patients (85.7 vs. 8.8%; P<0.001). Therefore, monitoring serum Abs against NY-ESO-1 by ELISA is an easy and feasible method. The high expression rate of NY-ESO-1-specific Abs in CRC patients indicates that measuring the levels of serum Abs against NY-ESO-1 may guide the treatment of NY-ESO-1-based specific immunotherapy for patients with advanced CRC. PMID:25187840

Neural correlates of improvements in personality and behavior following a neurological event.

PubMed

King, Marcie L; Manzel, Kenneth; Bruss, Joel; Tranel, Daniel

2017-11-21

Research on changes in personality and behavior following brain damage has focused largely on negative outcomes, such as increased irritability, moodiness, and social inappropriateness. However, clinical observations suggest that some patients may actually show positive personality and behavioral changes following a neurological event. In the current work, we investigated neuroanatomical correlates of positive personality and behavioral changes following a discrete neurological event (e.g., stroke, benign tumor resection). Patients (N = 97) were rated by a well-known family member or friend on five domains of personality and behavior: social behavior, irascibility, hypo-emotionality, distress, and executive functioning. Ratings were acquired during the chronic epoch of recovery, when psychological status was stabilized. We identified patients who showed positive changes in personality and behavior in one or more domains of functioning. Lesion analyses indicated that positive changes in personality and behavior were most consistently related to damage to the bilateral frontal polar regions and the right anterior dorsolateral prefrontal region. These findings support the conclusion that improvements in personality and behavior can occur after a neurological event, and that such changes have systematic neuroanatomical correlates. Patients who showed positive changes in personality and behavior following a neurological event were rated as having more disturbed functioning prior to the event. Our study may be taken as preliminary evidence that improvements in personality and behavior following a neurological event may involve dampening of (premorbidly) more extreme expressions of emotion. Copyright © 2017 Elsevier Ltd. All rights reserved.

Variability in personality expression across contexts: a social network approach.

PubMed

Clifton, Allan

2014-04-01

The current research investigated how the contextual expression of personality differs across interpersonal relationships. Two related studies were conducted with college samples (Study 1: N = 52, 38 female; Study 2: N = 111, 72 female). Participants in each study completed a five-factor measure of personality and constructed a social network detailing their 30 most important relationships. Participants used a brief Five-Factor Model scale to rate their personality as they experience it when with each person in their social network. Multiple informants selected from each social network then rated the target participant's personality (Study 1: N = 227, Study 2: N = 777). Contextual personality ratings demonstrated incremental validity beyond standard global self-report in predicting specific informants' perceptions. Variability in these contextualized personality ratings was predicted by the position of the other individuals within the social network. Across both studies, participants reported being more extraverted and neurotic, and less conscientious, with more central members of their social networks. Dyadic social network-based assessments of personality provide incremental validity in understanding personality, revealing dynamic patterns of personality variability unobservable with standard assessment techniques. © 2013 Wiley Periodicals, Inc.

An exploration of how positive emotions are expressed by older people and nurse assistants in homecare visits.

PubMed

Heyn, Lena; Ellington, Lee; Eide, Hilde

2017-11-01

We don´t know how positive emotions are being expressed by patients and health care providers in consultations. The aim of this study is to identify positive emotions expressed by older people and nurse assistants to discuss the function of these in the visits. This paper presents secondary analysis of consultations in the COMHOME project. In this pilot study, six transcribed consultations between nurse assistants and older people in home health care were analysed using a coding system for positive emotions with seven categories capturing both content and emotional intensity of positive affect. We found 114 expressions of positive emotions, 63% from nurse assistants and 37% from patients. Patients mostly expressed gratitude, indicating that patients are grateful for being helped. Nurse assistants mostly expressed Praise or Support, indicating that they gave their patients positive affirmation. The praise and support given by nurse assistants to older people in home health care seemed effective in fostering relationships and maintaining patient resilience. Thus, we claim that emotional talk in communication also should include positive emotions. Teaching health care providers about the importance of expressions of positive emotions should be integrated in communication skills training. Copyright © 2017 Elsevier B.V. All rights reserved.

[Correlations between OCT4 expression and clinicopathological factors and prognosis of patients with lung adenocarcinoma].

PubMed

Zhang, Xueyan; Wang, Huimin; Jin, Bo; Dong, Qianggang; Huang, Jinsu; Han, Baohui

2013-04-01

In recent years, cases of lung adenocarcinoma morbidity have consistently grown. OCT4 is the key gene that controls the automatic renewal of stem cells, and regulates the proliferation and differentiation of cancer stem cells. The aim of this study is to detect OCT4 expression in lung adenocarcinoma tissues, and to evaluate its relevance in the metastasis, chemotherapeutic effect, and prognosis in lung adenocarcinoma patients. Immunofluorescence method was employed to detect OCT4 expression in lung adenocarcinoma tissues. The relationship between OCT4 expression and clinical pathological indicators is examined through chi-square test. Moreover, the survival rate is calculated through the Kaplan-Meier survivorship curve. Finally, the relevance between the indicators and patient survival is estimated using Cox analysis. Among the 126 tissue samples of lung adenocarcinoma, 91 showed OCT4 positive cells. OCT4 expression is closely related to metastasis and chemoresistance in lung adenocarcinoma patients, and negatively corresponds to the patients' disease-free survival and survival periods. OCT4 expression is related to metastasis and chemoresistance in lung adenocarcinoma patients, and thus indicates poor prognosis.

Correct Hox gene expression established independently of position in Caenorhabditis elegans.

PubMed

Cowing, D; Kenyon, C

1996-07-25

The Hox genes are expressed in a conserved sequence of spatial domains along the anteroposterior (A/P) body axes of many organisms. In Drosophila, position-specific signals located along the A/P axis establish the pattern of Hox gene expression. In the nematode Caenorhabditis elegans, it is not known how the pattern of Hox gene expression is established. C. elegans uses lineal control mechanisms and local cell interactions to specify early blastomere identities. However, many cells expressing the same Hox gene are unrelated by lineage, suggesting that, as in Drosophila, domains of Hox gene expression may be defined by cell-extrinsic A/P positional signals. To test this, we have investigated whether posterior mesodermal and ectodermal cells will express their normal posterior Hox gene when they are mispositioned in the anterior. Surprisingly, we find that correct Hox gene expression does not depend on cell position, but is highly correlated with cell lineage. Thus, although the most striking feature of Hox gene expression is its positional specificity, in C. elegans the pattern is achieved, at least in part, by a lineage-specific control system that operates without regard to A/P position.

Peroxiredoxin 1 is a tumor-associated antigen in esophageal squamous cell carcinoma

PubMed Central

REN, PENGFEI; YE, HUA; DAI, LIPING; LIU, MEI; LIU, XINXIN; CHAI, YURONG; SHAO, QING; LI, YANG; LEI, NINGJING; PENG, BO; YAO, WU; ZHANG, JIANYING

2013-01-01

Peroxiredoxin 1 (Prdx1) is an antioxidant and plays an important role in H2O2-mediated cell signaling. We previously found that the expression level of Prdx1 was elevated in esophagus squamous cell carcinoma (ESCC) tissue using a proteomics approach. Since overexpressed protein can induce an autoimmune response, to further examine whether serum from ESCC patients exhibits immunoreactivity against Prdx1, autoantibody responses to Prdx1 were evaluated by ELISA, western blotting and indirect immunofluorescence assay in sera from patients with ESCC and normal individuals. Immunohistochemical study with tissue array slides and western blot analysis with cancer cell lines were also performed to analyze the protein expression profiles of Prdx1 in ESCC tissues and cancer cell lines. The results demonstrated that the positive rate of autoantibody against Prdx1 in ESCC sera was 13.2% (9/68), whereas this rate was 0% (0/89) in normal individuals. Data also showed that expression of Prdx1 was significantly increased in ESCC tissues when compared to expression in paired adjacent normal tissues (P<0.05). The data indicate that Prdx1 may contribute to malignant transformation of the esophagus, and may be used as a biomarker in the immunodiagnosis of ESCC. PMID:24009050

The Complete Loss of Tyrosine Kinase Receptors MET and RON Is a Poor Prognostic Factor in Patients with Extrahepatic Cholangiocarcinoma.

PubMed

Hayashi, Yuki; Yamaguchi, Junpei; Kokuryo, Toshio; Ebata, Tomoki; Yokoyama, Yukihiro; Igami, Tsuyoshi; Sugawara, Gen; Nagino, Masato

2016-12-01

Although the survival of patients with cholangiocarcinoma has improved, the prognosis remains unfavorable. The overexpression of mesenchymal-epithelial transition factor (MET) and recepteur d'origine nantais (RON) has been considered to be indicative of a poor prognosis in some types of cancer. On the other hand, some studies have shown that the expression of MET and RON is a favorable prognostic factor in certain types of tumors. Based on the immunohistochemical analysis of MET and RON, 290 patients who underwent resection for extrahepatic cholangiocarcinoma were divided into three groups: MET/RON-negative, -intermediate, and -positive. The associations between MET/RON expression and clinicopathological features, including prognosis, were analyzed. MET/RON-negativity was associated with nodal metastasis and advanced pathological stage. The overall 5-year survival rates were significantly lower in the MET/RON-negative and MET/RON-positive groups than in the MET/RON-intermediate group (28.3%, 32.4% and 48.5%, respectively; p=0.01). The complete loss of one or both MET and RON, as well as their overexpression, is a poor prognostic factor in patients with extrahepatic cholangiocarcinoma, probably due to the high rate of lymph-node metastasis. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

[Infant characteristics and anger reduction].

PubMed

Mischkulnig, M

1989-01-01

Konrad Lorenz first suggested in 1943 that certain physical and behavioral characteristics common to infants (babyishness) serve as cues to attract adult attention and care as well as to decrease the likelihood of aggression. The present study was designed to determine whether the visual stimuli of a baby's face alone are sufficient to reduce anger. The subjects were 60 female students between 18 and 30 years of age. Anger was evoked by setting unsolvable tasks and by noise and maintained by adequate instructions and by continuing noise. Three procedures of measurement (heart rate, retrospective self-report, and interpretation of facial affect by two observers) were designed to show the reactions of the subjects viewing photos of babies and adults. We found a slight increase in heart rate to be an expression of happiness and a massive acceleration to be an expression of anger. The self-report measures and interpretation of facial affect supported the hypothesis that there is a more positive response to infants than to adults, and to cute babies also a more positive one than to less attractive infants. We found weak evidence that babyishness reduces anger. As a consequence of the length of the experiment, subjects who should not be aroused became angry. Thus, it was possible to register a reduction of anger as reaction to cute infants.

B-cell posttransplant lymphoproliferative disorder isolated to the central nervous system is Epstein-Barr virus positive and lacks p53 and Myc expression by immunohistochemistry.

PubMed

Sundin, Andrew; Grzywacz, Bartosz J; Yohe, Sophia; Linden, Michael A; Courville, Elizabeth L

2017-03-01

In this retrospective study from one institution, we performed a clinicopathological study of a cohort of patients with posttransplant lymphoproliferative disorder (PTLD) confined to the central nervous system. We also identified a comparison cohort of patients with de novo primary diffuse large B-cell lymphoma of the central nervous system. We performed a detailed morphologic review, evaluated Epstein-Barr virus (EBV) by in situ hybridization, and interpreted a panel of immunohistochemical stains in a subset of cases including Hans classification markers (CD10, BCL6, MUM1), p53, CD30, Myc, and BCL2. All 17 of the posttransplant and none of 11 de novo cases were EBV positive (P < .005). Morphologic patterns identified in the PTLD cases were monomorphic diffuse large B-cell lymphoma pattern (10 patients) and "T-cell-rich" pattern (7 patients). The monomorphic posttransplant cases were more likely to be Myc negative (P = .015) and CD30 positive (P < .005) than the de novo cases, and showed a similarly low rate of p53 positivity by immunohistochemistry. No prognostic factors for overall survival were identified. Central nervous system PTLD is EBV positive, typically lacks p53 and Myc expression by immunohistochemistry, and can present with numerous background T lymphocytes. Copyright © 2016 Elsevier Inc. All rights reserved.

Characteristics of social anxiety from virtual interpersonal interactions in patients with schizophrenia.

PubMed

Park, Il Ho; Kim, Jae-Jin; Ku, Jeonghun; Jang, Hee Jeong; Park, Sung-Hyouk; Kim, Chan-Hyung; Kim, In Young; Kim, Sun I

2009-01-01

Dysfunctional emotional processing affects social functioning in patients with schizophrenia. However, the relationship between emotional perception and response in social interaction has not been elucidated. Twenty-seven patients with schizophrenia and 27 normal controls performed a virtual reality social encounter task in which they introduced themselves to avatars expressing happy, neutral, or angry emotions while verbal response duration and onset time were measured and perception of emotional valence and arousal, and state anxiety were rated afterwards. Self-reported trait-affective scale scores and the Positive and Negative Syndrome Scale (PANSS) ratings were also obtained. Patient group significantly underestimated the valence and arousal of angry emotions expressed by an avatar. While valence and arousal ratings of happy avatars were comparable between groups, patient group reported significantly higher state anxiety in response to happy avatars. State anxiety ratings significantly decreased from encounters with neutral to happy avatars in normal controls while no significant decrease was observed in the patient group. The Social Anhedonia Scale and PANSS negative symptom subscale scores (blunted affect, emotional withdrawal, and passive/ apathetic social withdrawal items) were significantly correlated with state anxiety ratings of the encounters with happy avatars. These results suggest that patients with schizophrenia have interference with the experience of pleasure in social interactions which may be associated with negative symptoms.

Proliferation Rates of Bovine Primary Muscle Cells Relate to Liveweight and Carcase Weight in Cattle

PubMed Central

Coles, Chantal A.; Wadeson, Jenny; Leyton, Carolina P.; Siddell, Jason P.; Greenwood, Paul L.; White, Jason D.; McDonagh, Matthew B.

2015-01-01

Muscling in cattle is largely influenced by genetic background, ultimately affecting beef yield and is of major interest to the beef industry. This investigation aimed to determine whether primary skeletal muscle cells isolated from different breeds of cattle with a varying genetic potential for muscling differ in their myogenic proliferative capacity. Primary skeletal muscle cells were isolated and cultured from the Longissimus muscle (LM) of 6 month old Angus, Hereford and Wagyu X Angus cattle. Cells were assessed for rate of proliferation and gene expression of PAX7, MYOD, MYF5, and MYOG. Proliferation rates were found to differ between breeds of cattle whereby myoblasts from Angus cattle were found to proliferate at a greater rate than those of Hereford and Wagyu X Angus during early stages of growth (5–20 hours in culture) in vitro (P < 0.05). The proliferation rates of myoblasts during early stages of culture in vitro were also found to be positively related to the liveweight and carcase weight of cattle (P < 0.05). Gene expression of MYF5 was also found to be significantly down-regulated in WagyuX compared with Angus cattle (P < 0.05). These findings suggest that early events during myogenesis are important for determining liveweight and caracase weights in cattle. PMID:25875203

Mucinous Colorectal Adenocarcinoma: Influence of EGFR and E-Cadherin Expression on Clinicopathologic Features and Prognosis.

PubMed

Foda, Abd AlRahman M; AbdelAziz, Azza; El-Hawary, Amira K; Hosni, Ali; Zalata, Khalid R; Gado, Asmaa I

2015-08-01

Previous studies have shown conflicting results on epidermal growth factor receptor (EGFR) and E-cadherin expression in colorectal carcinoma and their prognostic significance. To the best of our knowledge, this study is the first to investigate EGFR and E-cadherin expression, interrelation and relation to clinicopathologic, histologic parameters, and survival in rare colorectal mucinous adenocarcinoma (MA). In this study, we studied tumor tissue specimens from 150 patients with colorectal MA and nonmucinous adenocarcinoma (NMA). High-density manual tissue microarrays were constructed using modified mechanical pencil tips technique, and immunohistochemistry for EGFR and E-cadherin was performed. All relations were analyzed using established statistical methodologies. NMA expressed EGFR and E-cadherin in significantly higher rates with significant heterogenous pattern than MA. EGFR and E-cadherin positivity rates were significantly interrelated in both NMA and MA groups. In the NMA group, high EGFR expression was associated with old age, male sex, multiplicity of tumors, lack of mucinous component, and association with schistosomiasis. However, in the MA group, high EGFR expression was associated only with old age and MA subtype rather than signet ring carcinoma subtype. Conversely, high E-cadherin expression in MA cases was associated with old age, fungating tumor configuration, MA subtype, and negative intratumoral lymphocytic response. However, in the NMA cases, none of these factors was statistically significant. In a univariate analysis, neither EGFR nor E-cadherin expression showed a significant impact on disease-free or overall survival. Targeted therapy against EGFR and E-cadherin may not be useful in patients with MA. Neither EGFR nor E-cadherin is an independent prognostic factor in NMA or MA.

HER2 expression in oesophageal carcinoma and Barrett's oesophagus associated adenocarcinoma: An Australian study.

PubMed

Nagaraja, V; Shaw, N; Morey, A L; Cox, M R; Eslick, G D

2016-01-01

Several studies have evaluated the prognostic value of HER2 in oesophageal cancer, but the prognostic influence of HER2 overexpression in oesophageal cancer remains uncertain. The aim of this study was to assess the incidence of HER2 positivity and relationship with clinicopathological features in patients with oesophageal cancer. The study cohort consisted of 269 patients diagnosed with oesophageal carcinoma in a single institution. HER2 expression was analysed by immunohistochemistry (IHC) and silver in situ hybridization (SISH) in 152 archival oesophageal cancer specimens. Survival analysis was assessed using Hazard models. HER2 expression was IHC3+ in 14 (9.2%), IHC2+ in 14 (9.2%), IHC1+ in 57 (37.5%), and IHC0 in 67 (44.1%) cases. SISH results confirmed that 15 specimens (9.9%) were HER2 gene amplified. Among 27 squamous cell carcinomas (SCCs) only 3.7% were HER2 positive whereas 11.2% of 125 adenocarcinomas were HER2 positive. The HER2 positive tumours were more likely to occur in men (OR: 5.00, 95% CI: 1.69-14.29), smokers (OR: 10.00, 95% CI: 4.17-25) and in patients with Barrett's oesophagus (OR: 8.33, 95% CI: 3.71-20.00). There was no significant difference in survival between the (HER2 +ve, 14.3 months vs HER2 -ve, 24.6 months, p = 0.42) CONCLUSION: A HER2 prevalence rate of 9.9% was found among patients with oesophageal cancer and no correlation with survival was detected overall. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Heart rate monitoring in soccer: interest and limits during competitive match play and training, practical application.

PubMed

Alexandre, Dellal; da Silva, Cristiano Diniz; Hill-Haas, Stephen; Wong, Del P; Natali, Antonio J; De Lima, Jorge R P; Bara Filho, Mauricio G B; Marins, Joao J C B; Garcia, Emerson Silami; Karim, Chamari

2012-10-01

The identification of physiological loads imposed by soccer training or match play reveals essential information, which may help improve training and recovery strategies. Until today, the use of heart rate (HR) monitoring is not standardized in soccer. Thus, the aim of this review was to analyze, determine and compare the exercise intensity (EI) monitored by HR in professional, youth, and recreational soccer players during matches and training sessions using a meta-analysis. Heart rate is one of the most common physiological variables used to determine exercise internal training load. The mean EI recorded during competitive matches was described as 70-80% of VO2max or 80-90% of maximal heart rate (HRmax), independent of the playing level. With respect to HR training zones, approximately 65% of the total match duration is spent at intensity of 70-90% HRmax and rarely below 65% HRmax. However, although HRmax is mostly employed in the literature, monitoring EI should be expressed in relation to reserve heart rate, as it was described as a more reliable indicator of HR, allowing interindividual comparisons. The HR response according to the playing position indicates that midfielders are characterized by the highest EI, followed by forwards and fullbacks. Moreover, in the second half of the match, the EI is lower than that observed during the first half; this reduction could be correlated with the level of the player's physical conditioning. Consequently, coaches may favor the use of interval training or small-sided training games because these are shown to improve both aerobic capacity and the ability to repeat high-intensity actions. Small-sided games allow reaching similar HR responses to those found during interval training and match play but with greater heterogeneity values. Future investigations should include a larger sample of players with special reference to playing position and the expression of EI in percentage of the reserve heart rate, analyzing the possible intergender differences in HR response.

The correlation between pulmonary fibrosis and methylation of peripheral Smad3 in cases of pigeon breeder's lung in a Chinese Uygur population.

PubMed

Wu, Chao; Ding, Wei; Li, Qifeng; Wang, Wenyi; Deng, Mingqin; Jin, Rong; Pang, Baosen; Yang, Xiaohong

2017-06-27

Smad3 is a key protein in the transforming growth factor-beta (TGF-β)/Smad signaling pathway, which is involved in fibrosis in many organs. We investigated the relationship between Smad3 gene methylation and pulmonary fibrosis in pigeon breeder's lung (PBL). Twenty Uygur PBL patients with pulmonary fibrosis in Kashi between October 2015 and March 2016 were enrolled. Twenty PBL-free pigeon breeders and 20 healthy non-pigeon breeders enrolled during the same period constituted the negative and normal control groups, respectively. Participants' data and peripheral blood samples were collected, and three Smad3 CpG loci were examined. Distributions of CpG_2 and CpG_4 methylation rates did not differ across groups, whereas distributions of CpG_3 methylation rates were significantly different among the three groups. The CpG_3 methylation rate was significantly lower in the patient group than in the negative control group. Smad3 mRNA expression was significantly higher in the patient group than in the negative control group but did not differ between the two control groups. TGF-βlevels were significantly higher in the patient group than in either control group (both P<0.01). Smad3 gene methylation and Smad3 mRNA expression were negatively correlated, with a correlation coefficient of -0.84. The number of pigeons bred during the preceding three months was positively correlated with Smad3 mRNA expression, with a correlation coefficient of 0.77. Smad3 gene hypomethylation might promote pulmonary fibrosis in Uygur PBL patients via increased Smad3 mRNA expression. Smad3 methylation, Smad3 mRNA expression and TGF-β level were correlated with the number of pigeons bred by patients.

Evaluation of MMP-9 and MMP-2 and their suppressor TIMP-1 and TIMP-2 in adenocarcinoma of esophagogastric junction.

PubMed

Lu, Xiaofei; Duan, Lingling; Xie, Hongqin; Lu, Xiaoxia; Lu, Daolin; Lu, Daopeng; Jiang, Nan; Chen, Yuxin

2016-01-01

Adenocarcinoma of esophagogastric junction (AEG) is a lethal malignancy featured with early metastasis, poor prognosis, and few treatment options. Matrix metalloproteinase (MMP) and metalloproteinase suppressor (TIMP) have been considered to be associated with cancer invasion and metastasis. In our study, we evaluated expressions of MMP-9, MMP-2, TIMP-1, and TIMP-2 in AEG and their correlation with clinicopathological parameters and the overall survival rate. Expressions of MMP-9, MMP-2, TIMP-1, and TIMP-2 in specimens from 120 AEGs were detected by immunohistochemistry. The correlations between expressions of these four proteins and clinicopathological characters were analyzed by chi-square test. Moreover, the prognostic value of these four biomarkers was evaluated by univariate analysis with Kaplan-Meier method and multivariate analysis with Cox regression model. The positive expression rate of MMP-9, MMP-2, TIMP-1, and TIMP-2 was 65%, 53%, 70%, and 49%, respectively, in the detected 120 AEG samples. MMP-9 was significantly associated with poorly histological differentiation (P=0.001), lymph node metastasis (P=0.007), and UICC stage (P=0.008). TIMP-1 showed significantly reversed correlations with histological differentiation (P=0.001), lymph node metastasis (P=0.007), and Union for International Cancer Control stage (P=0.008). Univariate analysis revealed that lymph node metastasis (P=0.002), depth of invasion (P=0.050), and MMP-9+/TIMP-1 phonotype (P<0.001) were significantly associated with the overall survival rate. Multivariate analyses demonstrated that MMP-9+/TIMP-1-phenotype was an independent prognostic factor in AEGs. Detection of MMP-9 and TIMP-1 expression allows stratification of AEG patients into different survival categories and can be useful for precise individual evaluation and survival prediction.

Natural variation in PTB1 regulates rice seed setting rate by controlling pollen tube growth.

PubMed

Li, Shuangcheng; Li, Wenbo; Huang, Bin; Cao, Xuemei; Zhou, Xingyu; Ye, Shumei; Li, Chengbo; Gao, Fengyan; Zou, Ting; Xie, Kailong; Ren, Yun; Ai, Peng; Tang, Yangfan; Li, Xuemei; Deng, Qiming; Wang, Shiquan; Zheng, Aiping; Zhu, Jun; Liu, Huainian; Wang, Lingxia; Li, Ping

2013-01-01

Grain number, panicle seed setting rate, panicle number and grain weight are the most important components of rice grain yield. To date, several genes related to grain weight, grain number and panicle number have been described in rice. However, no genes regulating the panicle seed setting rate have been functionally characterized. Here we show that the domestication-related POLLEN TUBE BLOCKED 1 (PTB1), a RING-type E3 ubiquitin ligase, positively regulates the rice panicle seed setting rate by promoting pollen tube growth. The natural variation in expression of PTB1 which is affected by the promoter haplotype and the environmental temperature, correlates with the rice panicle seed setting rate. Our results support the hypothesis that PTB1 is an important maternal sporophytic factor of pollen tube growth and a key modulator of the rice panicle seed setting rate. This finding has implications for the improvement of rice yield.

Prohibitin promotes androgen receptor activation in ER-positive breast cancer

PubMed Central

Liu, Pengying; Xu, Yumei; Zhang, Wenwen; Li, Yan; Tang, Lin; Chen, Weiwei; Xu, Jing; Sun, Qian; Guan, Xiaoxiang

2017-01-01

ABSTRACT Prohibitin (PHB) is an evolutionarily conserved protein with multiple functions in both normal and cancer cells. Androgen receptor (AR) was reported to act as a different role in the ER-positive and ER-negative breast cancer. However, little is known about the role of PHB and whether PHB could regulate AR expression in the ER-positive breast cancer. Here, we determined the expression and clinical outcomes of PHB in breast cancer samples using 121 breast cancer tissues and published databases, and investigated the role of PHB in breast cancer cell growth, apoptosis and cell cycle arrest in the ER-positive breast cancer cells. We obtained the expression of PHB is significantly low in breast cancer samples, and low PHB expression positively correlated with poor prognosis of breast cancer. We detected that PHB could inhibit breast cancer cell proliferation, change cell cycle distribution and promote cell apoptosis in the ER-positive breast cancer cells. Moreover, we found PHB could significantly increase AR expression in both mRNA and protein levels in the ER-positive breast cancer cells. Additionally, a significant positive correlation between PHB and AR expression was identified in the 121 breast cancer tissues. PHB and AR expression are associated with prognosis in the ER-positive breast cancer patients. Our results indicate that PHB promotes AR activation in ER-positive breast cancer, making PHB and AR potential molecular targets for ER-positive breast cancer therapy. PMID:28272969

RNA/DNA ratio and LPL and MyoD mRNA expressions in muscle of Oreochromis niloticus fed with elevated levels of palm oil

NASA Astrophysics Data System (ADS)

Ayisi, Christian Larbi; Zhao, Jinliang

2016-02-01

Palm oil is of great potential as one of the sustainable alternatives to fish oil (FO) in aquafeeds. In this present study, five isonitrogenous diets (32% crude protein) with elevated palm oil levels of 0%, 2%, 4%, 6% and 8% were used during an 8-week feeding trial to evaluate its effects on RNA/DNA ratio and lipoprotein lipase (LPL) and MyoD mRNA expressions in muscle of Oreochromis niloticus. The results showed that RNA, DNA content as well as ratio of RNA to DNA were significantly affected ( P < 0.05), in each case the highest was recorded in fish group subjected to 6% palm oil level. There was a strong positive correlation between nucleic acid concentration (RNA concentration and RNA: DNA ratio) and specific growth rate (SGR), protein efficiency ratio (PER), while a negative correlation existed between nucleic acid concentration (RNA concentration and RNA: DNA ratio) and feed conversion ratio (FCR). The mRNA expressions of LPL and MyoD in muscle were not significantly affected by the different palm oil levels, although the highest expression was observed in fish fed with 6% palm oil level. There also existed a strong positive correlation between the mRNA expression of LPL, MyoD and SGR, PER, while their correlation with FCR was negative. In conclusion, elevated palm oil affected the RNA, DNA concentration as well as RNA/DNA ratio significantly, although the mRNA expression of LPL and MyoD were not affected significantly by elevated palm oil levels.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kanai, Dai; Ueda, Atsushi; Akagi, Tadayuki

Embryonic stem (ES) cells, derived from the inner cell mass of blastocysts, have a characteristic cell cycle with truncated G1 and G2 phases. Recent findings that suppression of Oct3/4 expression results in a reduced proliferation rate of ES cells suggest the involvement of Oct3/4 in the regulation of ES cell growth, although the underlying molecular mechanism remains unclear. In the present study, we identified E2F3a as a direct target gene of Oct3/4 in ES cells. Oct3/4 directly bound to the promoter region of the E2F3a gene and positively regulated expression of E2F3a in mouse ES cells. Suppression of E2F3a activitymore » by E2F6 overexpression led to the reduced proliferation in ES cells, which was relieved by co-expression of E2F3a. Furthermore, cell growth retardation caused by loss of Oct3/4 was rescued by E2F3a expression. These results suggest that Oct3/4 upregulates E2F3a expression to promote ES cell growth. - Highlights: • Oct3/4 positively regulates E2F3a expression in ES cells. • Oct3/4 binds to the promoter region of the E2F3a gene. • Overexpression of E2F6, an inhibitor of E2F3a, reduces ES cell growth. • E2F3a recovers growth retardation of ES cells caused by Oct3/4 reduction.« less

Macrophage Migration Inhibitory Factor Stimulates Angiogenic Factor Expression and Correlates With Differentiation and Lymph Node Status in Patients With Esophageal Squamous Cell Carcinoma

PubMed Central

Ren, Yi; Law, Simon; Huang, Xin; Lee, Ping Yin; Bacher, Michael; Srivastava, Gopesh; Wong, John

2005-01-01

Objective: The objectives of this study were: 1) to examine the expression of macrophage migration inhibitory factor (MIF) in esophageal squamous cell carcinoma (ESCC); 2) to see if a relationship exists between MIF expression, clinicopathologic features, and long-term prognosis; and 3) to ascertain the possible biologic function of MIF in angiogenesis. Summary Background Data: MIF has been linked to fundamental processes such as those controlling cell proliferation, cell survival, angiogenesis, and tumor progression. Its role in ESCC, and the correlation of MIF expression and tumor pathologic features in patients, has not been elucidated. Methods: The expression of MIF in tumor and nontumor tissues was examined by immunohistochemical staining. Concentrations of MIF, vascular endothelial growth factor (VEGF), and interleukin-8 (IL-8) in patients’ sera and in the supernatant of tumor cells culture were examined by ELISA. Correlations with clinicopathologic factors were made. Results: In 72 patients with ESCC, intracellular MIF was overexpressed in esophagectomy specimens. The expression of MIF correlated with both tumor differentiation and lymph node status. The median survival in the low-MIF expression group (<50% positively stained cancer cells on immunohistochemistry) and high expression group (≥50% positively stained cancer cells) was 28.3 months and 15.8 months, respectively (P = 0.03). The 3-year survival rates for the 2 groups were 37.7% and 12.1%, respectively. MIF expression was related to microvessel density; increased MIF serum levels also correlated with higher serum levels of VEGF. In addition, in vitro MIF stimulation of esophageal cancer cell lines induced a dose-dependent increase in VEGF and IL-8 secretion. Conclusions: These results demonstrate, for the first time, that human esophageal carcinomas express and secrete large amounts of MIF. Through its effects on VEGF and IL-8, MIF may serve as an autocrine factor in angiogenesis and thus play an important role in the pathogenesis of ESCC. PMID:15973102

Face-to-face: Perceived personal relevance amplifies face processing

PubMed Central

Pittig, Andre; Schupp, Harald T.; Alpers, Georg W.

2017-01-01

Abstract The human face conveys emotional and social information, but it is not well understood how these two aspects influence face perception. In order to model a group situation, two faces displaying happy, neutral or angry expressions were presented. Importantly, faces were either facing the observer, or they were presented in profile view directed towards, or looking away from each other. In Experiment 1 (n = 64), face pairs were rated regarding perceived relevance, wish-to-interact, and displayed interactivity, as well as valence and arousal. All variables revealed main effects of facial expression (emotional > neutral), face orientation (facing observer > towards > away) and interactions showed that evaluation of emotional faces strongly varies with their orientation. Experiment 2 (n = 33) examined the temporal dynamics of perceptual-attentional processing of these face constellations with event-related potentials. Processing of emotional and neutral faces differed significantly in N170 amplitudes, early posterior negativity (EPN), and sustained positive potentials. Importantly, selective emotional face processing varied as a function of face orientation, indicating early emotion-specific (N170, EPN) and late threat-specific effects (LPP, sustained positivity). Taken together, perceived personal relevance to the observer—conveyed by facial expression and face direction—amplifies emotional face processing within triadic group situations. PMID:28158672

Association of PCBs and allergies in children.

PubMed

Tsuji, Mayumi; Kawamoto, Toshihiro; Koriyama, Chihaya; Yamamoto, Megumi; Tsuchiya, Takuto; Matsumura, Fumio

2015-05-01

Recently, the incidence rates of childhood allergies have been rising around the world. The presence of persistent chemical pollutants in the environment and exposure to air pollutants are often cited as potential causes of childhood allergies. Accordingly, epidemiological studies of the associations between exposure to low levels of pollutants and adverse health effects are essential. However, at present no useful biomarkers for evaluating such associations have been developed. Thus, using a molecular epidemiological approach we planned to identify candidate biomarkers of pollutant-induced adverse health effects that can be used in children. In asthmatic children, we found that the serum levels of several polychlorinated biphenyl (PCB) congener sub-types were significantly positively correlated with interleukin (IL)-8 mRNA expression, whereas in a sub-group of children who displayed positive immunoglobulin E (IgE) responses to milk or egg proteins IL-22 mRNA expression was demonstrated to be useful for detecting the adverse health effects of environmental pollutants, particularly PCB congeners. In conclusion, the mRNA expression levels of IL-8 and IL-22 can be used to detect children who are at particular risk of adverse health events caused by environmental pollutants, especially PCBs. Copyright © 2014 Elsevier Inc. All rights reserved.

Autocrine signal transmission with extracellular ligand degradation

NASA Astrophysics Data System (ADS)

Muratov, C B; Posta, F; Shvartsman, S Y

2009-03-01

Traveling waves of cell signaling in epithelial layers orchestrate a number of important processes in developing and adult tissues. These waves can be mediated by positive feedback autocrine loops, a mode of cell signaling where binding of a diffusible extracellular ligand to a cell surface receptor can lead to further ligand release. We formulate and analyze a biophysical model that accounts for ligand-induced ligand release, extracellular ligand diffusion and ligand-receptor interaction. We focus on the case when the main mode for ligand degradation is extracellular and analyze the problem with the sharp threshold positive feedback nonlinearity. We derive expressions that link the speed of propagation and other characteristics of traveling waves to the parameters of the biophysical processes, such as diffusion rates, receptor expression level, etc. Analyzing the derived expressions we found that traveling waves in such systems can exhibit a number of unusual properties, e.g. non-monotonic dependence of the speed of propagation on ligand diffusivity. Our results for the fully developed traveling fronts can be used to analyze wave initiation from localized perturbations, a scenario that frequently arises in the in vitro models of epithelial wound healing, and guide future modeling studies of cell communication in epithelial layers.

[The expression of IDH1 (R132H) is positively correlated with cell proliferation and angiogenesis in glioma samples].

PubMed

Shi, Jiankuan; Zhao, Yuanlin; Yuan, Yuan; Wang, Chao; Xie, Zhonglin; Gao, Xing; Xiao, Liming; Ye, Jing

2016-03-01

To explore the correlations of the expression of mutant isocitrate dehydrogenase (IDH1) (R132H) protein with angiogenesis and cell proliferation in glioma. We performed polymerase chain reaction-based IDH gene mutation screening in 385 glioma samples, and the subcellular localization and expression levels of IDH1 (R132H) was examined by immunohistochemistry (IHC). Ki-67 labeling index was introduced to determine the proliferation of glioma cells, and the microvessel density was measured through CD34 staining. Statistical analyses were performed to show the correlations of IDH1 mutation with cell proliferation and microvessel density. The mutant rates of IDH1 were about 50%-60% in grade II-III gliomas and secondary glioblastomas, which were significantly higher than those in pilocytic astrocytoma (grade I) and primary glioblastoma (grade IV). Moreover, the level of IDH1 (R132H) protein was positively correlated with Ki-67 labeling index and microvessel density. IDH mutation was common in grade II-III glioma and secondary glioblastoma, and the mutant IDH1 (R132H) might play a critical role in the cell proliferation and angiogenesis of glioma.