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Sample records for highly aggressive cancer

  1. Src: marker or actor of prostate cancer aggressiveness

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    Virginie eVlaeminck-Guillem

    2014-08-01

    Full Text Available A key question for urologic practitioners is whether an apparently organ-confined prostate cancer is actually aggressive or not. The dilemma is to specifically identify among all prostate tumors the very aggressive high-grade cancers that will become life-threatening by developing extra-prostatic invasion and metastatic potential and the indolent cancers that will never modify a patient’s life expectancy. A choice must be made between several therapeutic options to achieve the optimal personalized management of the disease that causes as little harm as possible to patients. Reliable clinical, biological or pathological markers that would enable distinctions to be made between aggressive and indolen prostate cancers in routine practice at the time of initial diagnosis are still lacking. The molecular mechanisms that explain why a prostate cancer is aggressive or not are also poorly understood. Among the potential markers and/or actors in prostate cancer aggressiveness, Src and other members of the Src kinase family, are valuable candidates. Activation of Src-dependent intracellular pathways is frequently observed in prostate cancer. Indeed, Src is at the cross-roads of several pathways (including androgen receptor, TGFbeta, Bcl-2, Akt/PTEN or MAPK and ERK …, and is now known to influence some of the cellular and tissular events that accompany tumor progression: cell proliferation, cell motility, invasion, epithelial-to-mesenchymal transition, resistance to apoptosis, angiogenesis, neuroendocrine differentiation, and metastatic spread. Recent work even suggests that Src could also play a part in prostate cancer initiation in coordination with the androgen receptor. The aim of this review is to gather data that explores the links between the Src kinase family and prostate cancer progression and aggressiveness.

  2. Methylome-wide Sequencing Detects DNA Hypermethylation Distinguishing Indolent from Aggressive Prostate Cancer

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    Jeffrey M. Bhasin

    2015-12-01

    Full Text Available A critical need in understanding the biology of prostate cancer is characterizing the molecular differences between indolent and aggressive cases. Because DNA methylation can capture the regulatory state of tumors, we analyzed differential methylation patterns genome-wide among benign prostatic tissue and low-grade and high-grade prostate cancer and found extensive, focal hypermethylation regions unique to high-grade disease. These hypermethylation regions occurred not only in the promoters of genes but also in gene bodies and at intergenic regions that are enriched for DNA-protein binding sites. Integration with existing RNA-sequencing (RNA-seq and survival data revealed regions where DNA methylation correlates with reduced gene expression associated with poor outcome. Regions specific to aggressive disease are proximal to genes with distinct functions from regions shared by indolent and aggressive disease. Our compendium of methylation changes reveals crucial molecular distinctions between indolent and aggressive prostate cancer.

  3. Impact of meat consumption, preparation, and mutagens on aggressive prostate cancer.

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    Sanoj Punnen

    Full Text Available The association between meat consumption and prostate cancer remains unclear, perhaps reflecting heterogeneity in the types of tumors studied and the method of meat preparation--which can impact the production of carcinogens.We address both issues in this case-control study focused on aggressive prostate cancer (470 cases and 512 controls, where men reported not only their meat intake but also their meat preparation and doneness level on a semi-quantitative food-frequency questionnaire. Associations between overall and grilled meat consumption, doneness level, ensuing carcinogens and aggressive prostate cancer were assessed using multivariate logistic regression.Higher consumption of any ground beef or processed meats were positively associated with aggressive prostate cancer, with ground beef showing the strongest association (OR = 2.30, 95% CI:1.39-3.81; P-trend = 0.002. This association primarily reflected intake of grilled or barbequed meat, with more well-done meat conferring a higher risk of aggressive prostate cancer. Comparing high and low consumptions of well/very well cooked ground beef to no consumption gave OR's of 2.04 (95% CI:1.41-2.96 and 1.51 (95% CI:1.06-2.14, respectively. In contrast, consumption of rare/medium cooked ground beef was not associated with aggressive prostate cancer. Looking at meat mutagens produced by cooking at high temperatures, we detected an increased risk with 2-amino-3,8-Dimethylimidazo-[4,5-f]Quinolaxine (MelQx and 2-amino-3,4,8-trimethylimidazo(4,5-fqunioxaline (DiMelQx, when comparing the highest to lowest quartiles of intake: OR = 1.69 (95% CI:1.08-2.64;P-trend = 0.02 and OR = 1.53 (95% CI:1.00-2.35; P-trend = 0.005, respectively.Higher intake of well-done grilled or barbequed red meat and ensuing carcinogens could increase the risk of aggressive prostate cancer.

  4. SRC: marker or actor in prostate cancer aggressiveness.

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    Vlaeminck-Guillem, Virginie; Gillet, Germain; Rimokh, Ruth

    2014-01-01

    A key question for urologic practitioners is whether an apparently organ-confined prostate cancer (PCa) is actually aggressive or not. The dilemma is to specifically identify among all prostate tumors the very aggressive high-grade cancers that will become life-threatening by developing extra-prostatic invasion and metastatic potential and the indolent cancers that will never modify a patient's life expectancy. A choice must be made between several therapeutic options to achieve the optimal personalized management of the disease that causes as little harm as possible to patients. Reliable clinical, biological, or pathological markers that would enable distinctions to be made between aggressive and indolent PCas in routine practice at the time of initial diagnosis are still lacking. The molecular mechanisms that explain why a PCa is aggressive or not are also poorly understood. Among the potential markers and/or actors in PCa aggressiveness, Src and other members of the Src kinase family, are valuable candidates. Activation of Src-dependent intracellular pathways is frequently observed in PCa. Indeed, Src is at the cross-roads of several pathways [including androgen receptor (AR), TGFbeta, Bcl-2, Akt/PTEN or MAPK, and ERK …], and is now known to influence some of the cellular and tissular events that accompany tumor progression: cell proliferation, cell motility, invasion, epithelial-to-mesenchymal transition, resistance to apoptosis, angiogenesis, neuroendocrine differentiation, and metastatic spread. Recent work even suggests that Src could also play a part in PCa initiation in coordination with the AR. The aim of this review is to gather data that explore the links between the Src kinase family and PCa progression and aggressiveness.

  5. Blood-based biomarkers of aggressive prostate cancer.

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    Men Long Liong

    Full Text Available PURPOSE: Prostate cancer is a bimodal disease with aggressive and indolent forms. Current prostate-specific-antigen testing and digital rectal examination screening provide ambiguous results leading to both under-and over-treatment. Accurate, consistent diagnosis is crucial to risk-stratify patients and facilitate clinical decision making as to treatment versus active surveillance. Diagnosis is currently achieved by needle biopsy, a painful procedure. Thus, there is a clinical need for a minimally-invasive test to determine prostate cancer aggressiveness. A blood sample to predict Gleason score, which is known to reflect aggressiveness of the cancer, could serve as such a test. MATERIALS AND METHODS: Blood mRNA was isolated from North American and Malaysian prostate cancer patients/controls. Microarray analysis was conducted utilizing the Affymetrix U133 plus 2·0 platform. Expression profiles from 255 patients/controls generated 85 candidate biomarkers. Following quantitative real-time PCR (qRT-PCR analysis, ten disease-associated biomarkers remained for paired statistical analysis and normalization. RESULTS: Microarray analysis was conducted to identify 85 genes differentially expressed between aggressive prostate cancer (Gleason score ≥8 and controls. Expression of these genes was qRT-PCR verified. Statistical analysis yielded a final seven-gene panel evaluated as six gene-ratio duplexes. This molecular signature predicted as aggressive (ie, Gleason score ≥8 55% of G6 samples, 49% of G7(3+4, 79% of G7(4+3 and 83% of G8-10, while rejecting 98% of controls. CONCLUSION: In this study, we have developed a novel, blood-based biomarker panel which can be used as the basis of a simple blood test to identify men with aggressive prostate cancer and thereby reduce the overdiagnosis and overtreatment that currently results from diagnosis using PSA alone. We discuss possible clinical uses of the panel to identify men more likely to benefit from

  6. Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error.

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    Shipitsin, M; Small, C; Choudhury, S; Giladi, E; Friedlander, S; Nardone, J; Hussain, S; Hurley, A D; Ernst, C; Huang, Y E; Chang, H; Nifong, T P; Rimm, D L; Dunyak, J; Loda, M; Berman, D M; Blume-Jensen, P

    2014-09-09

    Key challenges of biopsy-based determination of prostate cancer aggressiveness include tumour heterogeneity, biopsy-sampling error, and variations in biopsy interpretation. The resulting uncertainty in risk assessment leads to significant overtreatment, with associated costs and morbidity. We developed a performance-based strategy to identify protein biomarkers predictive of prostate cancer aggressiveness and lethality regardless of biopsy-sampling variation. Prostatectomy samples from a large patient cohort with long follow-up were blindly assessed by expert pathologists who identified the tissue regions with the highest and lowest Gleason grade from each patient. To simulate biopsy-sampling error, a core from a high- and a low-Gleason area from each patient sample was used to generate a 'high' and a 'low' tumour microarray, respectively. Using a quantitative proteomics approach, we identified from 160 candidates 12 biomarkers that predicted prostate cancer aggressiveness (surgical Gleason and TNM stage) and lethal outcome robustly in both high- and low-Gleason areas. Conversely, a previously reported lethal outcome-predictive marker signature for prostatectomy tissue was unable to perform under circumstances of maximal sampling error. Our results have important implications for cancer biomarker discovery in general and development of a sampling error-resistant clinical biopsy test for prediction of prostate cancer aggressiveness.

  7. In Vivo Detection of HSP90 Identifies Breast Cancers with Aggressive Behavior.

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    Osada, Takuya; Kaneko, Kensuke; Gwin, William R; Morse, Michael A; Hobeika, Amy; Pogue, Brian W; Hartman, Zachary C; Hughes, Philip F; Haystead, Timothy; Lyerly, H Kim

    2017-12-15

    Purpose: Hsp90, a chaperone to numerous molecular pathways in malignant cells, is elevated in aggressive breast cancers. We hypothesized that identifying breast cells with elevated Hsp90 activity in situ could result in early detection of aggressive breast cancers. Experimental Design: We exploited the uptake of an Hsp90 inhibitor by malignant cells to create an imaging probe (HS131) of Hsp90 activity by linking it to a near-infrared (nIR) dye. HS131 uptake into cells correlated with cell membrane expression of Hsp90 and was used to image molecular subtypes of murine and human breast cancers in vitro and in murine models. Results: HS131 imaging was both sensitive and specific in detecting the murine 4T1 breast cancer cell line, as well as subclones with differing metastatic potential. Highly metastatic subclones (4T07) had high HS131 uptake, but subclones with lower metastatic potential (67NR, 168FARN) had low HS131 uptake. We generated isogenic cell lines to demonstrate that overexpression of a variety of specific oncogenes resulted in high HS131 uptake and retention. Finally, we demonstrated that HS131 could be used to detect spontaneous tumors in MMTV-neu mice, as well as primary and metastatic human breast cancer xenografts. HS131 could image invasive lobular breast cancer, a histologic subtype of breast cancer which is often undetectable by mammography. Conclusions: An HSP90-targeting nIR probe is sensitive and specific in imaging all molecular subtypes of murine and human breast cancer, with higher uptake in aggressive and highly metastatic clones. Clinical studies with Hsp90-targeting nIR probes will be initiated shortly. Clin Cancer Res; 23(24); 7531-42. ©2017 AACR . ©2017 American Association for Cancer Research.

  8. Mitochondrial mutations drive prostate cancer aggression

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    Hopkins, Julia F.; Sabelnykova, Veronica Y.; Weischenfeldt, Joachim

    2017-01-01

    Nuclear mutations are well known to drive tumor incidence, aggression and response to therapy. By contrast, the frequency and roles of mutations in the maternally inherited mitochondrial genome are poorly understood. Here we sequence the mitochondrial genomes of 384 localized prostate cancer...... in prostate cancer, and suggest interplay between nuclear and mitochondrial mutational profiles in prostate cancer....

  9. A systems genetics approach identifies CXCL14, ITGAX, and LPCAT2 as novel aggressive prostate cancer susceptibility genes.

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    Kendra A Williams

    2014-11-01

    Full Text Available Although prostate cancer typically runs an indolent course, a subset of men develop aggressive, fatal forms of this disease. We hypothesize that germline variation modulates susceptibility to aggressive prostate cancer. The goal of this work is to identify susceptibility genes using the C57BL/6-Tg(TRAMP8247Ng/J (TRAMP mouse model of neuroendocrine prostate cancer. Quantitative trait locus (QTL mapping was performed in transgene-positive (TRAMPxNOD/ShiLtJ F2 intercross males (n = 228, which facilitated identification of 11 loci associated with aggressive disease development. Microarray data derived from 126 (TRAMPxNOD/ShiLtJ F2 primary tumors were used to prioritize candidate genes within QTLs, with candidate genes deemed as being high priority when possessing both high levels of expression-trait correlation and a proximal expression QTL. This process enabled the identification of 35 aggressive prostate tumorigenesis candidate genes. The role of these genes in aggressive forms of human prostate cancer was investigated using two concurrent approaches. First, logistic regression analysis in two human prostate gene expression datasets revealed that expression levels of five genes (CXCL14, ITGAX, LPCAT2, RNASEH2A, and ZNF322 were positively correlated with aggressive prostate cancer and two genes (CCL19 and HIST1H1A were protective for aggressive prostate cancer. Higher than average levels of expression of the five genes that were positively correlated with aggressive disease were consistently associated with patient outcome in both human prostate cancer tumor gene expression datasets. Second, three of these five genes (CXCL14, ITGAX, and LPCAT2 harbored polymorphisms associated with aggressive disease development in a human GWAS cohort consisting of 1,172 prostate cancer patients. This study is the first example of using a systems genetics approach to successfully identify novel susceptibility genes for aggressive prostate cancer. Such

  10. Prostate Health Index improves multivariable risk prediction of aggressive prostate cancer.

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    Loeb, Stacy; Shin, Sanghyuk S; Broyles, Dennis L; Wei, John T; Sanda, Martin; Klee, George; Partin, Alan W; Sokoll, Lori; Chan, Daniel W; Bangma, Chris H; van Schaik, Ron H N; Slawin, Kevin M; Marks, Leonard S; Catalona, William J

    2017-07-01

    To examine the use of the Prostate Health Index (PHI) as a continuous variable in multivariable risk assessment for aggressive prostate cancer in a large multicentre US study. The study population included 728 men, with prostate-specific antigen (PSA) levels of 2-10 ng/mL and a negative digital rectal examination, enrolled in a prospective, multi-site early detection trial. The primary endpoint was aggressive prostate cancer, defined as biopsy Gleason score ≥7. First, we evaluated whether the addition of PHI improves the performance of currently available risk calculators (the Prostate Cancer Prevention Trial [PCPT] and European Randomised Study of Screening for Prostate Cancer [ERSPC] risk calculators). We also designed and internally validated a new PHI-based multivariable predictive model, and created a nomogram. Of 728 men undergoing biopsy, 118 (16.2%) had aggressive prostate cancer. The PHI predicted the risk of aggressive prostate cancer across the spectrum of values. Adding PHI significantly improved the predictive accuracy of the PCPT and ERSPC risk calculators for aggressive disease. A new model was created using age, previous biopsy, prostate volume, PSA and PHI, with an area under the curve of 0.746. The bootstrap-corrected model showed good calibration with observed risk for aggressive prostate cancer and had net benefit on decision-curve analysis. Using PHI as part of multivariable risk assessment leads to a significant improvement in the detection of aggressive prostate cancer, potentially reducing harms from unnecessary prostate biopsy and overdiagnosis. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

  11. Effect of Statins and Anticoagulants on Prostate Cancer Aggressiveness

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    Alizadeh, Moein; Sylvestre, Marie-Pierre; Zilli, Thomas; Van Nguyen, Thu; Guay, Jean-Pierre; Bahary, Jean-Paul; Taussky, Daniel

    2012-01-01

    Purpose: Statins and anticoagulants (ACs) have both been associated with a less-aggressive prostate cancer (PCa) and a better outcome after treatment of localized PCa. The results of these studies might have been confounded because patients might often take both medications. We examined their respective influence on PCa aggressiveness at initial diagnosis. Materials and Methods: We analyzed 381 patients treated with either external beam radiotherapy or brachytherapy for low-risk (n = 152), intermediate-risk (n = 142), or high-risk (n = 87) localized PCa. Univariate and multivariate logistic regression analyses were used to investigate an association between these drug classes and prostate cancer aggressiveness. We tested whether the concomitant use of statins and ACs had a different effect than that of either AC or statin use alone. Results: Of the 381 patients, 172 (45.1%) were taking statins and 141 (37.0%) ACs; 105 patients (27.6%) used both. On univariate analysis, the statin and AC users were associated with the prostate-specific antigen (PSA) level (p = .017) and National Comprehensive Cancer Network risk group (p = .0022). On multivariate analysis, statin use was associated with a PSA level 20 ng/mL (odds ratio, 0.29; 95% confidence interval, 0.08–0.83; p = .03). The use of ACs was associated with a PSA level >20 ng/mL (odds ratio, 0.13; 95% confidence interval, 0.02–0.59, p = .02). Conclusion: Both AC and statins have an effect on PCa aggressiveness, with statins having a more stringent relationship with the PSA level, highlighting the importance of considering statin use in studies of PCa aggressiveness.

  12. Effect of Statins and Anticoagulants on Prostate Cancer Aggressiveness

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    Alizadeh, Moein [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, Quebec (Canada); Sylvestre, Marie-Pierre [Research Center, Department of Statistics, University of Montreal, Montreal, Quebec (Canada); Zilli, Thomas; Van Nguyen, Thu; Guay, Jean-Pierre; Bahary, Jean-Paul [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, Quebec (Canada); Taussky, Daniel, E-mail: daniel.taussky.chum@ssss.gouv.qc.ca [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, Quebec (Canada)

    2012-07-15

    Purpose: Statins and anticoagulants (ACs) have both been associated with a less-aggressive prostate cancer (PCa) and a better outcome after treatment of localized PCa. The results of these studies might have been confounded because patients might often take both medications. We examined their respective influence on PCa aggressiveness at initial diagnosis. Materials and Methods: We analyzed 381 patients treated with either external beam radiotherapy or brachytherapy for low-risk (n = 152), intermediate-risk (n = 142), or high-risk (n = 87) localized PCa. Univariate and multivariate logistic regression analyses were used to investigate an association between these drug classes and prostate cancer aggressiveness. We tested whether the concomitant use of statins and ACs had a different effect than that of either AC or statin use alone. Results: Of the 381 patients, 172 (45.1%) were taking statins and 141 (37.0%) ACs; 105 patients (27.6%) used both. On univariate analysis, the statin and AC users were associated with the prostate-specific antigen (PSA) level (p = .017) and National Comprehensive Cancer Network risk group (p = .0022). On multivariate analysis, statin use was associated with a PSA level <10 ng/mL (odds ratio, 2.9; 95% confidence interval, 1.3-6.8; p = .012) and a PSA level >20 ng/mL (odds ratio, 0.29; 95% confidence interval, 0.08-0.83; p = .03). The use of ACs was associated with a PSA level >20 ng/mL (odds ratio, 0.13; 95% confidence interval, 0.02-0.59, p = .02). Conclusion: Both AC and statins have an effect on PCa aggressiveness, with statins having a more stringent relationship with the PSA level, highlighting the importance of considering statin use in studies of PCa aggressiveness.

  13. Biotinidase is a novel marker for papillary thyroid cancer aggressiveness.

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    Anthony K-C So

    Full Text Available Biotinidase was identified in secretome analysis of thyroid cancer cell lines using proteomics. The goal of the current study was to analyze the expression of biotinidase in thyroid cancer tissues and fine needle aspiration (FNA samples to evaluate its diagnostic and prognostic potential in thyroid cancer. Immunohistochemical analysis of biotinidase was carried out in 129 papillary thyroid cancer (PTC, 34 benign thyroid tissues and 43 FNA samples and correlated with patients' prognosis. Overall biotinidase expression was decreased in PTC compared to benign nodules (p = 0.001. Comparison of aggressive and non-aggressive PTC showed decrease in overall biotinidase expression in the former (p = 0.001. Loss of overall biotinidase expression was associated with poor disease free survival (p = 0.019, Hazards ratio (HR = 3.1. We examined the effect of subcellular compartmentalization of nuclear and cytoplasmic biotinidase on patient survival. Decreased nuclear expression of biotinidase was observed in PTC as compared to benign tissues (p<0.001. Upon stratification within PTC, nuclear expression was reduced in aggressive as compared to non-aggressive tumors (p<0.001. Kaplan-Meier survival analysis showed significant association of loss of nuclear biotinidase expression with reduced disease free survival (p = 0.014, HR = 5.4. Cytoplasmic biotinidase expression was reduced in aggressive thyroid cancers in comparison with non-aggressive tumors (p = 0.002, Odds ratio (OR = 0.29 which was evident by its significant association with advanced T stage (p = 0.003, OR = 0.28, nodal metastasis (p<0.001, OR = 0.16, advanced TNM stage (p<0.001, OR = 0.21 and extrathyroidal extension (p = 0.001, OR = 0.23. However, in multivariate analysis extrathyroidal extension emerged as the most significant prognostic marker for aggressive thyroid carcinomas (p = 0.015, HR = 12.8. In conclusion, loss of overall

  14. Lack of association between obesity and aggressiveness of differentiated thyroid cancer.

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    Grani, G; Lamartina, L; Montesano, T; Ronga, G; Maggisano, V; Falcone, R; Ramundo, V; Giacomelli, L; Durante, C; Russo, D; Maranghi, M

    2018-04-17

    Aim of this study was to evaluate the association between body mass index (BMI) and aggressive features of differentiated thyroid cancer (DTC) in a prospective cohort. Patients with DTC were prospectively enrolled at a tertiary referral center and grouped according to their BMI. Aggressive clinic-pathological features were analyzed following the American Thyroid Association Initial Risk Stratification System score. The cohort was composed of 432 patients: 5 (1.2%) were underweight, 187 (43.3%) normal weight, 154 (35.6%) overweight, 68 (15.7%) grade 1 obese, 11 (2.5%) grade 2 obese and 7 (1.6%) grade 3 obese. No single feature of advanced thyroid cancer was more frequent in obese patients than in others. No significant correlation was found between BMI, primary tumor size (Spearman's ρ - 0.02; p = 0.71) and ATA Initial Risk Stratification System score (ρ 0.03; p = 0.49), after adjustment for age. According to the multivariate logistic regression analysis, male gender and pre-surgical diagnosis of cancer were significant predictors of cancer with high or intermediate-high recurrence risk according to the ATA system (OR 2.06 and 2.51, respectively), while older age at diagnosis was a protective factor (OR 0.98), and BMI was not a predictor. BMI was a predictor of microscopic extrathyroidal extension only (OR 1.06). Obesity was not associated with aggressive features in this prospective, European cohort of patients with DTC.

  15. Hypoxia Induced Tumor Metabolic Switch Contributes to Pancreatic Cancer Aggressiveness

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    Vasseur, Sophie; Tomasini, Richard; Tournaire, Roselyne; Iovanna, Juan L. [INSERM U624, Stress Cellulaire, Parc Scientifique et Technologique de Luminy, 163 Avenue de Luminy, BP 915,13288 Marseille cedex 9 (France)

    2010-12-16

    Pancreatic ductal adenocarcinoma remains one of the most lethal of all solid tumors with an overall five-year survival rate of only 3–5%. Its aggressive biology and resistance to conventional and targeted therapeutic agents lead to a typical clinical presentation of incurable disease once diagnosed. The disease is characterized by the presence of a dense stroma of fibroblasts and inflammatory cells, termed desmoplasia, which limits the oxygen diffusion in the organ, creating a strong hypoxic environment within the tumor. In this review, we argue that hypoxia is responsible for the highly aggressive and metastatic characteristics of this tumor and drives pancreatic cancer cells to oncogenic and metabolic changes facilitating their proliferation. However, the molecular changes leading to metabolic adaptations of pancreatic cancer cells remain unclear. Cachexia is a hallmark of this disease and illustrates that this cancer is a real metabolic disease. Hence, this tumor must harbor metabolic pathways which are probably tied in a complex inter-organ dialog during the development of this cancer. Such a hypothesis would better explain how under fuel source limitation, pancreatic cancer cells are maintained, show a growth advantage, and develop metastasis.

  16. Hypoxia Induced Tumor Metabolic Switch Contributes to Pancreatic Cancer Aggressiveness

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    Vasseur, Sophie; Tomasini, Richard; Tournaire, Roselyne; Iovanna, Juan L.

    2010-01-01

    Pancreatic ductal adenocarcinoma remains one of the most lethal of all solid tumors with an overall five-year survival rate of only 3–5%. Its aggressive biology and resistance to conventional and targeted therapeutic agents lead to a typical clinical presentation of incurable disease once diagnosed. The disease is characterized by the presence of a dense stroma of fibroblasts and inflammatory cells, termed desmoplasia, which limits the oxygen diffusion in the organ, creating a strong hypoxic environment within the tumor. In this review, we argue that hypoxia is responsible for the highly aggressive and metastatic characteristics of this tumor and drives pancreatic cancer cells to oncogenic and metabolic changes facilitating their proliferation. However, the molecular changes leading to metabolic adaptations of pancreatic cancer cells remain unclear. Cachexia is a hallmark of this disease and illustrates that this cancer is a real metabolic disease. Hence, this tumor must harbor metabolic pathways which are probably tied in a complex inter-organ dialog during the development of this cancer. Such a hypothesis would better explain how under fuel source limitation, pancreatic cancer cells are maintained, show a growth advantage, and develop metastasis

  17. Molecular targeted therapies of aggressive thyroid cancer

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    Silvia Martina eFerrari

    2015-11-01

    Full Text Available Differentiated thyroid carcinomas (DTC that arise from follicular cells account > 90% of thyroid cancer (TC [papillary thyroid cancer (PTC 90%, follicular thyroid cancer (FTC 10%], while medullary thyroid cancer (MTC accounts < 5%. Complete total thyroidectomy is the treatment of choice for PTC, FTC and MTC. Radioiodine is routinely recommended in high-risk patients and considered in intermediate risk DTC patients. DTC cancer cells, during tumor progression, may lose the iodide uptake ability, becoming resistant to radioiodine, with a significant worsening of the prognosis. The lack of specific and effective drugs for aggressive and metastatic DTC and MTC leads to additional efforts towards the development of new drugs.Several genetic alterations in different molecular pathways in TC have been shown in the last decades, associated with TC development and progression. Rearranged during transfection (RET/PTC gene rearrangements, RET mutations, BRAF mutations, RAS mutations, and vascular endothelial growth factor receptor 2 angiogenesis pathways are some of the known pathways determinant in the development of TC. Tyrosine kinase inhibitors (TKIs are small organic compounds inhibiting tyrosine kinases auto-phosphorylation and activation, most of them are multikinase inhibitors. TKIs act on the above-mentioned molecular pathways involved in growth, angiogenesis, local and distant spread of TC. TKIs are emerging as new therapies of aggressive TC, including DTC, MTC and anaplastic thyroid cancer (ATC, being capable of inducing clinical responses and stabilization of disease. Vandetanib and cabozantinib have been approved for the treatment of MTC, while sorafenib and lenvatinib for DTC refractory to radioiodine. These drugs prolong median progression-free survival, but until now no significant increase has been observed on overall survival; side effects are common. New efforts are made to find new more effective and safe compounds, and to personalize

  18. Identifying aggressive prostate cancer foci using a DNA methylation classifier.

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    Mundbjerg, Kamilla; Chopra, Sameer; Alemozaffar, Mehrdad; Duymich, Christopher; Lakshminarasimhan, Ranjani; Nichols, Peter W; Aron, Manju; Siegmund, Kimberly D; Ukimura, Osamu; Aron, Monish; Stern, Mariana; Gill, Parkash; Carpten, John D; Ørntoft, Torben F; Sørensen, Karina D; Weisenberger, Daniel J; Jones, Peter A; Duddalwar, Vinay; Gill, Inderbir; Liang, Gangning

    2017-01-12

    Slow-growing prostate cancer (PC) can be aggressive in a subset of cases. Therefore, prognostic tools to guide clinical decision-making and avoid overtreatment of indolent PC and undertreatment of aggressive disease are urgently needed. PC has a propensity to be multifocal with several different cancerous foci per gland. Here, we have taken advantage of the multifocal propensity of PC and categorized aggressiveness of individual PC foci based on DNA methylation patterns in primary PC foci and matched lymph node metastases. In a set of 14 patients, we demonstrate that over half of the cases have multiple epigenetically distinct subclones and determine the primary subclone from which the metastatic lesion(s) originated. Furthermore, we develop an aggressiveness classifier consisting of 25 DNA methylation probes to determine aggressive and non-aggressive subclones. Upon validation of the classifier in an independent cohort, the predicted aggressive tumors are significantly associated with the presence of lymph node metastases and invasive tumor stages. Overall, this study provides molecular-based support for determining PC aggressiveness with the potential to impact clinical decision-making, such as targeted biopsy approaches for early diagnosis and active surveillance, in addition to focal therapy.

  19. A basal stem cell signature identifies aggressive prostate cancer phenotypes

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    Smith, Bryan A.; Sokolov, Artem; Uzunangelov, Vladislav; Baertsch, Robert; Newton, Yulia; Graim, Kiley; Mathis, Colleen; Cheng, Donghui; Stuart, Joshua M.; Witte, Owen N.

    2015-01-01

    Evidence from numerous cancers suggests that increased aggressiveness is accompanied by up-regulation of signaling pathways and acquisition of properties common to stem cells. It is unclear if different subtypes of late-stage cancer vary in stemness properties and whether or not these subtypes are transcriptionally similar to normal tissue stem cells. We report a gene signature specific for human prostate basal cells that is differentially enriched in various phenotypes of late-stage metastatic prostate cancer. We FACS-purified and transcriptionally profiled basal and luminal epithelial populations from the benign and cancerous regions of primary human prostates. High-throughput RNA sequencing showed the basal population to be defined by genes associated with stem cell signaling programs and invasiveness. Application of a 91-gene basal signature to gene expression datasets from patients with organ-confined or hormone-refractory metastatic prostate cancer revealed that metastatic small cell neuroendocrine carcinoma was molecularly more stem-like than either metastatic adenocarcinoma or organ-confined adenocarcinoma. Bioinformatic analysis of the basal cell and two human small cell gene signatures identified a set of E2F target genes common between prostate small cell neuroendocrine carcinoma and primary prostate basal cells. Taken together, our data suggest that aggressive prostate cancer shares a conserved transcriptional program with normal adult prostate basal stem cells. PMID:26460041

  20. Contrast-enhanced dynamic and diffusion-weighted MR imaging at 3.0 T to assess aggressiveness of bladder cancer

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    Zhou, Guoxing, E-mail: sheasthospital@163.com [Department of Radiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120 (China); Chen, Xiao, E-mail: chx_win@163.com [Department of Radiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120 (China); Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029 (China); Zhang, Jianhua [Department of Radiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120 (China); Zhu, Jingqi, E-mail: zjh1830@easthospital.cn [Department of Radiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120 (China); Zong, Genlin, E-mail: zgl0577@easthospital.cn [Department of Radiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120 (China); Wang, Zhongqiu, E-mail: zhq2001us@163.com [Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029 (China)

    2014-11-15

    Highlights: • Wash out rate is associated with the aggressiveness of bladder cancer (BC). • Apparent diffusion coefficient (ADC) value could be used to assess the aggressiveness of BC. • The diagnostic accuracy of aggressiveness of BC using ADC was better than semi-quantitative parameters. • Our data showed a good diagnostic performance of ADC and wash-out together in assessing BC aggressiveness. - Abstract: Background: Diffusion weighted magnetic resonance imaging (DWI) and dynamic contrast-enhanced (DCE) MRI have been considered useful for pathological staging and histological grading in bladder cancer. To our knowledge, no study has combined the two imaging modalities together to assess aggressiveness of bladder cancer. Objective: To assess the clinical aggressiveness of bladder cancer with DCE MRI and DWI at 3.0 T. Materials and methods: A total of 59 patients with 69 pathologically confirmed tumor lesions were included in this study. All patients underwent MR examination at 3.0 T basing on DWI and DCE imaging. Tumor staging and histological grade were evaluated. The aggressiveness of bladder cancer was classified as low-, intermediate-, or high-aggressiveness according to its pathological phenotype. Apparent diffusion coefficient (ADC) value and semi-quantitative parameters (wash-in rate and wash-out rate) were determined. The correlation between clinical aggressiveness and ADC value, wash-in rate and wash-out rate were analyzed. In addition, the diagnostic accuracy of the diffusion and semi-quantitative parameters were estimated using receiver operating characteristic curve (ROC). Results: Aggressiveness of bladder cancer is negatively correlated with ADC value (r = −0.705, p < 0.0001) and wash-out rate (r = −0.719, p < 0.0001). The tumor ADC value is positively correlated with wash-out rate (r = 0.555, p < 0.0001). The diagnostic specificity and accuracy using tumor ADC value and wash-out for the tumor with size <24 mm were better than that

  1. Contrast-enhanced dynamic and diffusion-weighted MR imaging at 3.0 T to assess aggressiveness of bladder cancer

    International Nuclear Information System (INIS)

    Zhou, Guoxing; Chen, Xiao; Zhang, Jianhua; Zhu, Jingqi; Zong, Genlin; Wang, Zhongqiu

    2014-01-01

    Highlights: • Wash out rate is associated with the aggressiveness of bladder cancer (BC). • Apparent diffusion coefficient (ADC) value could be used to assess the aggressiveness of BC. • The diagnostic accuracy of aggressiveness of BC using ADC was better than semi-quantitative parameters. • Our data showed a good diagnostic performance of ADC and wash-out together in assessing BC aggressiveness. - Abstract: Background: Diffusion weighted magnetic resonance imaging (DWI) and dynamic contrast-enhanced (DCE) MRI have been considered useful for pathological staging and histological grading in bladder cancer. To our knowledge, no study has combined the two imaging modalities together to assess aggressiveness of bladder cancer. Objective: To assess the clinical aggressiveness of bladder cancer with DCE MRI and DWI at 3.0 T. Materials and methods: A total of 59 patients with 69 pathologically confirmed tumor lesions were included in this study. All patients underwent MR examination at 3.0 T basing on DWI and DCE imaging. Tumor staging and histological grade were evaluated. The aggressiveness of bladder cancer was classified as low-, intermediate-, or high-aggressiveness according to its pathological phenotype. Apparent diffusion coefficient (ADC) value and semi-quantitative parameters (wash-in rate and wash-out rate) were determined. The correlation between clinical aggressiveness and ADC value, wash-in rate and wash-out rate were analyzed. In addition, the diagnostic accuracy of the diffusion and semi-quantitative parameters were estimated using receiver operating characteristic curve (ROC). Results: Aggressiveness of bladder cancer is negatively correlated with ADC value (r = −0.705, p < 0.0001) and wash-out rate (r = −0.719, p < 0.0001). The tumor ADC value is positively correlated with wash-out rate (r = 0.555, p < 0.0001). The diagnostic specificity and accuracy using tumor ADC value and wash-out for the tumor with size <24 mm were better than that

  2. Molecular biology of breast cancer metastasis Molecular expression of vascular markers by aggressive breast cancer cells

    International Nuclear Information System (INIS)

    Hendrix, Mary JC; Seftor, Elisabeth A; Kirschmann, Dawn A; Seftor, Richard EB

    2000-01-01

    During embryogenesis, the formation of primary vascular networks occurs via the processes of vasculogenesis and angiogenesis. In uveal melanoma, vasculogenic mimicry describes the 'embryonic-like' ability of aggressive, but not nonaggressive, tumor cells to form networks surrounding spheroids of tumor cells in three-dimensional culture; these recapitulate the patterned networks seen in patients' aggressive tumors and correlates with poor prognosis. The molecular profile of these aggressive tumor cells suggests that they have a deregulated genotype, capable of expressing vascular phenotypes. Similarly, the embryonic-like phenotype expressed by the aggressive human breast cancer cells is associated with their ability to express a variety of vascular markers. These studies may offer new insights for consideration in breast cancer diagnosis and therapeutic intervention strategies

  3. Overexpression of the A Disintegrin and Metalloproteinase ADAM15 is linked to a Small but Highly Aggressive Subset of Prostate Cancers

    Directory of Open Access Journals (Sweden)

    Christoph Burdelski

    2017-04-01

    Full Text Available The A Disintegrin and Metalloproteinase (ADAM family of endopeptidases plays a role in many solid cancers and includes promising targets for anticancer therapies. Deregulation of ADAM15 has been linked to tumor aggressiveness and cell line studies suggest that ADAM15 overexpression may also be implicated in prostate cancer. To evaluate the impact of ADAM15 expression and its relationship with key genomic alterations, a tissue microarray containing 12,427 prostate cancers was analyzed by immunohistochemistry. ADAM15 expression was compared to phenotype, prognosis and molecular features including TMPRSS2:ERG fusion and frequent deletions involving PTEN, 3p, 5q and 6q. Normal prostate epithelium did not show ADAM15 staining. In prostate cancers, negative, weak, moderate, and strong ADAM15 staining was found in 87.7%, 3.7%, 5.6%, and 3.0% of 9826 interpretable tumors. Strong ADAM15 staining was linked to high Gleason grade, advanced pathological tumor stage, positive nodal stage and resection margin. ADAM15 overexpression was also associated with TMPRSS2:ERG fusions and PTEN deletions (P < .0001 but unrelated to deletions of 3p, 5q and 6q. In univariate analysis, high ADAM15 expression was strongly linked to PSA recurrence (P < .0001. However, in multivariate analyses this association was only maintained if the analysis was limited to preoperatively available parameters in ERG-negative cancers. The results of our study demonstrate that ADAM15 is strongly up regulated in a small but highly aggressive fraction of prostate cancers. In these tumors, ADAM15 may represent a suitable drug target. In a preoperative scenario, ADAM15 expression measurement may assist prognosis assessment, either alone or in combination with other markers.

  4. Loss of PDEF, a prostate-derived Ets factor is associated with aggressive phenotype of prostate cancer: Regulation of MMP 9 by PDEF

    Directory of Open Access Journals (Sweden)

    Meacham Randall B

    2010-06-01

    Full Text Available Abstract Background Prostate-derived Ets factor (PDEF is expressed in tissues of high epithelial content including prostate, although its precise function has not been fully established. Conventional therapies produce a high rate of cure for patients with localized prostate cancer, but there is, at present, no effective treatment for intervention in metastatic prostate cancer. These facts underline the need to develop new approaches for early diagnosis of aggressive prostate cancer patients, and mechanism based anti-metastasis therapies that will improve the outlook for hormone-refractory prostate cancer. In this study we evaluated role of prostate-derived Ets factor (PDEF in prostate cancer. Results We observed decreased PDEF expression in prostate cancer cell lines correlated with increased aggressive phenotype, and complete loss of PDEF protein in metastatic prostate cancer cell lines. Loss of PDEF expression was confirmed in high Gleason Grade prostate cancer samples by immuno-histochemical methods. Reintroduction of PDEF profoundly affected cell behavior leading to less invasive phenotypes in three dimensional cultures. In addition, PDEF expressing cells had altered cell morphology, decreased FAK phosphorylation and decreased colony formation, cell migration, and cellular invasiveness. In contrast PDEF knockdown resulted in increased migration and invasion as well as clonogenic activity. Our results also demonstrated that PDEF downregulated MMP9 promoter activity, suppressed MMP9 mRNA expression, and resulted in loss of MMP9 activity in prostate cancer cells. These results suggested that loss of PDEF might be associated with increased MMP9 expression and activity in aggressive prostate cancer. To confirm results we investigated MMP9 expression in clinical samples of prostate cancer. Results of these studies show increased MMP9 expression correlated with advanced Gleason grade. Taken together our results demonstrate decreased PDEF expression

  5. No Effect of NGAL/lipocalin-2 on Aggressiveness of Cancer in the MMTV-PyMT/FVB/N Mouse Model for Breast Cancer

    DEFF Research Database (Denmark)

    Cramer, Elisabeth P; Glenthøj, Andreas; Häger, Mattias

    2012-01-01

    tumor volume, or to the number of metastases. Histology and gelatinolytic activity of the mammary tumors did not differ between wild-type and lipocalin-2-deficient mice. We conclude that NGAL/lipocalin-2 does not invariably affect the aggressiveness of breast cancers as assessed in mouse models, thus......NGAL/lipocalin-2 is a siderophore-binding protein that is highly expressed in several cancers. It is suggested to confer a proliferative advantage to cancer cells. Its expression has been correlated with aggressiveness of breast cancer as determined both in patients and in mouse breast cancer...... models. This was recently confirmed in two mouse models of spontaneous breast cancer in wild-type and lipocalin-2-deficient mice. We used a similar strategy using a different mouse strain. Lipocalin-2-deficient mice and mouse mammary tumor virus-polyoma middle T antigen (MMTV-PyMT) mice were crossed...

  6. The biological age linked to oxidative stress modifies breast cancer aggressiveness.

    Science.gov (United States)

    Sáez-Freire, María Del Mar; Blanco-Gómez, Adrián; Castillo-Lluva, Sonia; Gómez-Vecino, Aurora; Galvis-Jiménez, Julie Milena; Martín-Seisdedos, Carmen; Isidoro-García, María; Hontecillas-Prieto, Lourdes; García-Cenador, María Begoña; García-Criado, Francisco Javier; Patino-Alonso, María Carmen; Galindo-Villardón, Purificación; Mao, Jian-Hua; Prieto, Carlos; Castellanos-Martín, Andrés; Kaderali, Lars; Pérez-Losada, Jesús

    2018-03-14

    The incidence of breast cancer increases with age until menopause, and breast cancer is more aggressive in younger women. The existence of epidemiological links between breast cancer and aging indicates that both processes share some common mechanisms of development. Oxidative stress is associated with both cancer susceptibility and aging. Here we observed that ERBB2-positive breast cancer, which developed in genetically heterogeneous ERBB2-positive transgenic mice generated by a backcross, is more aggressive in chronologically younger than in older mice (differentiated by the median survival of the cohort that was 79 weeks), similar to what occurs in humans. In this cohort, we estimated the oxidative biological age using a mathematical model that integrated several subphenotypes directly or indirectly related to oxidative stress. The model selected the serum levels of HDL-cholesterol and magnesium and total AKT1 and glutathione concentrations in the liver. The grade of aging was calculated as the difference between the predicted biological age and the chronological age. This comparison permitted the identification of biologically younger and older mice compared with their chronological age. Interestingly, biologically older mice developed more aggressive breast cancer than the biologically younger mice. Genomic regions on chromosomes 2 and 15 linked to the grade of oxidative aging were identified. The levels of expression of Zbp1 located on chromosome 2, a gene related to necroptosis and inflammation, positively correlated with the grade of aging and tumour aggressiveness. Moreover, the pattern of gene expression of genes linked to the inflammation and the response to infection pathways was enriched in the livers of biologically old mice. This study shows part of the complex interactions between breast cancer and aging. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Diagnosis of medullary thyroid cancer and prognostic factors of disease aggressiveness

    Directory of Open Access Journals (Sweden)

    D O Gazizova

    2013-12-01

    Full Text Available In the study were enrolled 137 patients with medullary thyroid cancer (MTC. Low 35%-sensitivity of FNAC and high accuracy of basal calcitonin in MTC diagnostics were found. Mutation analysis of the RET pro- tooncogene in familial and sporadic MTC, RAS -gene in sporadic MTC were done. The correlation between type of the mutation and disease aggressiveness was found.

  8. Polygenic hazard score to guide screening for aggressive prostate cancer

    DEFF Research Database (Denmark)

    Seibert, Tyler M; Fan, Chun Chieh; Wang, Yunpeng

    2018-01-01

    . These polymorphisms were incorporated into a survival analysis to estimate their effects on age at diagnosis of aggressive PCa (that is, not eligible for surveillance according to National Comprehensive Cancer Network guidelines; any of Gleason score ≥7, stage T3-T4, PSA (prostate specific antigen) concentration ≥10......OBJECTIVES: To develop and validate a genetic tool to predict age of onset of aggressive prostate cancer (PCa) and to guide decisions of who to screen and at what age. DESIGN: Analysis of genotype, PCa status, and age to select single nucleotide polymorphisms (SNPs) associated with diagnosis...

  9. Ploidy, cytokinetics, and histology features of aggressive versus less aggressive uterine cervical squamous cell carcinomas

    International Nuclear Information System (INIS)

    Johnson, T.S.; Peters, L.J.; Adelson, M.; Williamson, K.D.; Sneige, N.; Katz, R.L.; Freedman, R.S.

    1985-01-01

    The authors are investigating the interrelationships of flow cytometric measured ploidy, S-fraction with histology features of uterine cervical squamous cell cancers in an attempt to identify aggressive, high risk tumors and less aggressive tumors. Experimentally, pre-radiotherapy biopsy specimens are being studied using flow ploidy and cell-cycle analysis and microscopic scoring for histology features. The results to date for some 200 patients indicate that there are identifyable aggressive tumors, at high risk for 2 yr local control within each stage of disease and differentiation category (WD, MD, PD). These aggressive tumors usually have high degree DNA abnormalities (triploid or greater), high proliferative activity (%S≥20) compared to the less aggressive tumors characterized by diploid/near diploid DNA content, low to moderate %S (2-19, mean 12). Expression of high S-fraction appears to reflect high growth activity or growth potential and characterizes the aggressive tumors

  10. BRCA1-IRIS Overexpression Promotes Formation of Aggressive Breast Cancers

    Science.gov (United States)

    Shimizu, Yoshiko; Luk, Hugh; Horio, David; Miron, Penelope; Griswold, Michael; Iglehart, Dirk; Hernandez, Brenda; Killeen, Jeffrey; ElShamy, Wael M.

    2012-01-01

    Introduction Women with HER2+ or triple negative/basal-like (TN/BL) breast cancers succumb to their cancer rapidly due, in part to acquired Herceptin resistance and lack of TN/BL-targeted therapies. BRCA1-IRIS is a recently discovered, 1399 residue, BRCA1 locus alternative product, which while sharing 1365 residues with the full-length product of this tumor suppressor gene, BRCA1/p220, it has oncoprotein-like properties. Here, we examine whether BRCA1-IRIS is a valuable treatment target for HER2+ and/or TN/BL tumors. Methodology/Principal Findings Immunohistochemical staining of large cohort of human breast tumor samples using new monoclonal anti-BRCA1-IRIS antibody, followed by correlation of BRCA1-IRIS expression with that of AKT1, AKT2, p-AKT, survivin and BRCA1/p220, tumor status and age at diagnosis. Generation of subcutaneous tumors in SCID mice using human mammary epithelial (HME) cells overexpressing TERT/LT/BRCA1-IRIS, followed by comparing AKT, survivin, and BRCA1/p220 expression, tumor status and aggressiveness in these tumors to that in tumors developed using TERT/LT/RasV12-overexpressing HME cells. Induction of primary and invasive rat mammary tumors using the carcinogen N-methyl-N-nitrosourea (NMU), followed by analysis of rat BRCA1-IRIS and ERα mRNA levels in these tumors. High BRCA1-IRIS expression was detected in the majority of human breast tumors analyzed, which was positively correlated with that of AKT1-, AKT2-, p-AKT-, survivin, but negatively with BRCA1/p220 expression. BRCA1-IRIS-positivity induced high-grade, early onset and metastatic HER2+ or TN/BL tumors. TERT/LT/BRCA1-IRIS overexpressing HME cells formed invasive subcutaneous tumors that express high AKT1, AKT2, p-AKT and vimentin, but no CK19, p63 or BRCA1/p220. NMU-induced primary and invasive rat breast cancers expressed high levels of rat BRCA1-IRIS mRNA but low levels of rat ERα mRNA. Conclusion/Significance BRCA1-IRIS overexpression triggers aggressive breast tumor formation

  11. Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error

    OpenAIRE

    Shipitsin, M; Small, C; Choudhury, S; Giladi, E; Friedlander, S; Nardone, J; Hussain, S; Hurley, A D; Ernst, C; Huang, Y E; Chang, H; Nifong, T P; Rimm, D L; Dunyak, J; Loda, M

    2014-01-01

    Background: Key challenges of biopsy-based determination of prostate cancer aggressiveness include tumour heterogeneity, biopsy-sampling error, and variations in biopsy interpretation. The resulting uncertainty in risk assessment leads to significant overtreatment, with associated costs and morbidity. We developed a performance-based strategy to identify protein biomarkers predictive of prostate cancer aggressiveness and lethality regardless of biopsy-sampling variation. Methods: Prostatectom...

  12. Identification of markers associated with highly aggressive metastatic phenotypes using quantitative comparative proteomics

    DEFF Research Database (Denmark)

    Terp, Mikkel Green; Lund, Rikke Raaen; Jensen, Ole Nørregaard

    2012-01-01

    The spread of cancer cells from a primary tumor to form metastases at distant sites is a complex process that remains poorly defined. Certain tumor cells are more aggressive and thus lead to rapid development of multiple distant metastases. Here, we identify proteins associated with these aggress......The spread of cancer cells from a primary tumor to form metastases at distant sites is a complex process that remains poorly defined. Certain tumor cells are more aggressive and thus lead to rapid development of multiple distant metastases. Here, we identify proteins associated...

  13. Loss of PTEN expression is associated with aggressive behavior and poor prognosis in Middle Eastern triple-negative breast cancer.

    Science.gov (United States)

    Beg, Shaham; Siraj, Abdul K; Prabhakaran, Sarita; Jehan, Zeenath; Ajarim, Dahish; Al-Dayel, Fouad; Tulbah, Asma; Al-Kuraya, Khawla S

    2015-06-01

    PTEN is a tumor suppressor that negatively regulates the PI3 K-AKT signaling pathway which is involved in the pathogenesis of many different tumor types and serves as a prognostic marker in breast cancer. However, the significance of the role of PTEN in Middle Eastern ethnic breast cancer has not been explored especially with the fact that breast cancer originating from this ethnic population tend to behave more aggressively than breast cancer in the west. In this study, we analyzed PTEN alteration in a tissue microarray format containing more than 1000 primary breast cancers with clinical follow-up data. Tissue Microarray sections were analyzed for protein expression and copy number change using immunohistochemistry and fluorescence in situ hybridization. Loss of PTEN immunostaining was observed in 77 % of the cases. PTEN loss was significantly associated with large tumor size (p = 0.0030), high grade (p = 0.0281), tumor recurrence (p = 0.0333), and triple-negative breast cancers (p = 0.0086). PTEN loss in triple-negative breast cancers was significantly associated with rapid tumor cell proliferation (p = 0.0396) and poor prognosis (p = 0.0408). PTEN deletion was found only in 60 cases (6.4 %). Loss of PTEN protein expression occurs at high frequency in Middle Eastern breast cancer. PTEN inactivation may potentially lead to an aggressive behavior of tumor cells through stimulation of tumor cell proliferation. Furthermore, PTEN signaling pathway might be used as potential therapeutic target in triple-negative breast cancers since loss of its expression is shown to be significantly associated with this aggressive subtype of breast cancer.

  14. Effect of naloxone on food competition aggression in food-restricted high and low aggression pigeons (Columba livia

    Directory of Open Access Journals (Sweden)

    Fachinelli C.

    2004-01-01

    Full Text Available We determined the effect of the opiate receptor antagonist naloxone on aggression, emotion, feeder control, and eating behavior in high and low aggression female pigeons maintained at 80% of their normal weight and exposed to food competition interactions. Pigeons were divided into pairs by previously ranked high aggression (total time spent in offensive aggression exceeding 60 s/5 min; N = 6 pairs and low aggression females (time spent in offensive aggression less than 10 s/5 min; N = 6 pairs. A pigeon in each pair received an sc dose of naloxone (1 mg kg-1 ml saline-1 and the other animal received the vehicle. Trials (10 min were performed 30 min after the naloxone/vehicle administration. The naloxone group of high aggression pigeons showed lower scores of total time spent in offensive aggression (control: 98.6 ± 12.0; naloxone: 46.8 ± 6.6 s; P < 0.05 and higher scores of time spent in emotional responses (control: 3.5 ± 0.6; naloxone: 10.8 ± 2.4 s; P < 0.05 than controls. The other behaviors scored, feeder control and eating behavior, were not affected in this group. The naloxone group of low aggression pigeons, however, showed higher scores of offensive aggression than their controls (5.3 ± 1.3; naloxone: 28.7 ± 8.0 s; P < 0.05. The present results suggest that opiate receptor mechanisms are implicated in offensive aggression responses in high and low aggression pigeons. However, as reported for brain 5-hydroxytryptamine manipulation and GABA-A-benzodiazepine receptor manipulation, the effect of the opiate receptor antagonist on food competition aggression in pigeons was related to their pretreatment level of aggression.

  15. Association between Plasma 25-Hydroxyvitamin D, Ancestry and Aggressive Prostate Cancer among African Americans and European Americans in PCaP.

    Directory of Open Access Journals (Sweden)

    Susan E Steck

    Full Text Available African Americans (AAs have lower circulating 25-hydroxyvitamin D3 [25(OHD3] concentrations and higher prostate cancer (CaP aggressiveness than other racial/ethnic groups. The purpose of the current study was to examine the relationship between plasma 25(OHD3, African ancestry and CaP aggressiveness among AAs and European Americans (EAs.Plasma 25(OHD3 was measured using LC-MS/MS (Liquid Chromatography Tandem Mass Spectrometry in 537 AA and 663 EA newly-diagnosed CaP patients from the North Carolina-Louisiana Prostate Cancer Project (PCaP classified as having either 'high' or 'low' aggressive disease based on clinical stage, Gleason grade and prostate specific antigen at diagnosis. Mean plasma 25(OHD3 concentrations were compared by proportion of African ancestry. Logistic regression was used to calculate multivariable adjusted odds ratios (OR and 95% confidence intervals (95%CI for high aggressive CaP by tertile of plasma 25(OHD3.AAs with highest percent African ancestry (>95% had the lowest mean plasma 25(OHD3 concentrations. Overall, plasma 25(OHD3 was associated positively with aggressiveness among AA men, an association that was modified by calcium intake (ORT 3vs.T1: 2.23, 95%CI: 1.26-3.95 among men with low calcium intake, and ORT 3vs.T1: 0.19, 95%CI: 0.05-0.70 among men with high calcium intake. Among EAs, the point estimates of the ORs were <1.0 for the upper tertiles with CIs that included the null.Among AAs, plasma 25(OHD3 was associated positively with CaP aggressiveness among men with low calcium intake and inversely among men with high calcium intake. The clinical significance of circulating concentrations of 25(OHD3 and interactions with calcium intake in the AA population warrants further study.

  16. EpCAM nuclear localization identifies aggressive Thyroid Cancer and is a marker for poor prognosis

    Directory of Open Access Journals (Sweden)

    MacMillan Christina

    2010-06-01

    Full Text Available Abstract Background Proteolytic cleavage of the extracellular domain (EpEx of Epithelial cell adhesion molecule (EpCAM and nuclear signaling by its intracellular oncogenic domain Ep-ICD has recently been implicated in increased proliferation of cancer cells. The clinical significance of Ep-ICD in human tumors remains an enigma. Methods EpEx, Ep-ICD and β-catenin immunohistochemistry using specific antibodies was conducted on 58 archived thyroid cancer (TC tissue blocks from 34 patients and correlated with survival analysis of these patients for up to 17 years. Results The anaplastic (ATC and aggressive thyroid cancers showed loss of EpEx and increased nuclear and cytoplasmic accumulation of Ep-ICD. In contrast, the low grade papillary thyroid cancers (PTC showed membranous EpEx and no detectable nuclear Ep-ICD. The ATC also showed concomitant nuclear expression of Ep-ICD and β-catenin. Kaplan-Meier Survival analysis revealed reduced overall survival (OS for TC patients showing nuclear Ep-ICD expression or loss of membranous EpEx (p Conclusion We report reciprocal loss of membrane EpEx but increased nuclear and cytoplasmic accumulation of Ep-ICD in aggressive TC; nuclear Ep-ICD correlated with poor OS of TC patients. Thus nuclear Ep-ICD localization may serve as a useful biomarker for aggressive TC and may represent a novel diagnostic, prognostic and therapeutic target for aggressive TC.

  17. A feasibility study for enrichment of highly aggressive cancer subpopulations by their biophysical properties via dielectrophoresis enhanced with synergistic fluid flow.

    Science.gov (United States)

    Douglas, Temple Anne; Cemazar, Jaka; Balani, Nikita; Sweeney, Daniel C; Schmelz, Eva M; Davalos, Rafael V

    2017-06-01

    A common problem with cancer treatment is the development of treatment resistance and tumor recurrence that result from treatments that kill most tumor cells yet leave behind aggressive cells to repopulate. Presented here is a microfluidic device that can be used to isolate tumor subpopulations to optimize treatment selection. Dielectrophoresis (DEP) is a phenomenon where particles are polarized by an electric field and move along the electric field gradient. Different cell subpopulations have different DEP responses depending on their bioelectrical phenotype, which, we hypothesize, correlate with aggressiveness. We have designed a microfluidic device in which a region containing posts locally distorts the electric field created by an AC voltage and forces cells toward the posts through DEP. This force is balanced with a simultaneous drag force from fluid motion that pulls cells away from the posts. We have shown that by adjusting the drag force, cells with aggressive phenotypes are influenced more by the DEP force and trap on posts while others flow through the chip unaffected. Utilizing single-cell trapping via cell-sized posts coupled with a drag-DEP force balance, we show that separation of similar cell subpopulations may be achieved, a result that was previously impossible with DEP alone. Separated subpopulations maintain high viability downstream, and remain in a native state, without fluorescent labeling. These cells can then be cultured to help select a therapy that kills aggressive subpopulations equally or better than the bulk of the tumor, mitigating resistance and recurrence. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Early-onset baldness and the risk of aggressive prostate cancer: findings from a case-control study.

    Science.gov (United States)

    Papa, Nathan P; MacInnis, Robert J; English, Dallas R; Bolton, Damien; Davis, Ian D; Lawrentschuk, Nathan; Millar, Jeremy L; Severi, Gianluca; Hopper, John L; Giles, Graham G

    2018-01-01

    We aimed to evaluate the associations between androgenetic alopecia at a young age and subsequent development of aggressive prostate cancer (PC). Using a case-control design with self-administered questionnaire, we evaluated the association between aggressive PC and very early-onset balding at age 20, and early-onset balding at age 40 years in 1,941 men. Cases were men with high-grade and/or advanced stage cancer and controls were clinic based men who had undergone biopsy and were found to be histologically cancer negative. Additionally, for cases we assessed whether early-onset balding was associated with earlier onset of disease. Men with very early-onset balding at age 20 years were at increased risk for subsequent aggressive PC [odds ratio (OR) 1.51, 95% confidence interval (CI) 1.07-2.12] after adjustment for age at baseline, family history of PC, smoking status, alcohol intake, body shape, timing of growth spurt and ejaculatory frequency. Additionally, these men were diagnosed with PC approximately 16 months earlier than cases without the exposure. The effect was present particularly for men with advanced stage pT3+ disease (OR 1.68, 95% CI 1.14-2.47) while men with organ-confined high-grade (8-10) PC did not exhibit the same relationship. No significant associations were observed for men who were balding at age 40 years, given no balding at age 20. Men with androgenetic alopecia at age 20 years are at increased risk of advanced stage PC. This small subset of men are potentially candidates for earlier screening and urological follow-up.

  19. Clinical evaluation of a computer-aided diagnosis system for determining cancer aggressiveness in prostate MRI

    International Nuclear Information System (INIS)

    Litjens, Geert J.S.; Barentsz, Jelle O.; Karssemeijer, Nico; Huisman, Henkjan J.

    2015-01-01

    To investigate the added value of computer-aided diagnosis (CAD) on the diagnostic accuracy of PIRADS reporting and the assessment of cancer aggressiveness. Multi-parametric MRI and histopathological outcome of MR-guided biopsies of a consecutive set of 130 patients were included. All cases were prospectively PIRADS reported and the reported lesions underwent CAD analysis. Logistic regression combined the CAD prediction and radiologist PIRADS score into a combination score. Receiver-operating characteristic (ROC) analysis and Spearman's correlation coefficient were used to assess the diagnostic accuracy and correlation to cancer grade. Evaluation was performed for discriminating benign lesions from cancer and for discriminating indolent from aggressive lesions. In total 141 lesions (107 patients) were included for final analysis. The area-under-the-ROC-curve of the combination score was higher than for the PIRADS score of the radiologist (benign vs. cancer, 0.88 vs. 0.81, p = 0.013 and indolent vs. aggressive, 0.88 vs. 0.78, p < 0.01). The combination score correlated significantly stronger with cancer grade (0.69, p = 0.0014) than the individual CAD system or radiologist (0.54 and 0.58). Combining CAD prediction and PIRADS into a combination score has the potential to improve diagnostic accuracy. Furthermore, such a combination score has a strong correlation with cancer grade. (orig.)

  20. EpCAM nuclear localization identifies aggressive Thyroid Cancer and is a marker for poor prognosis

    International Nuclear Information System (INIS)

    Ralhan, Ranju; Cao, Jun; Lim, Terence; MacMillan, Christina; Freeman, Jeremy L; Walfish, Paul G

    2010-01-01

    Proteolytic cleavage of the extracellular domain (EpEx) of Epithelial cell adhesion molecule (EpCAM) and nuclear signaling by its intracellular oncogenic domain Ep-ICD has recently been implicated in increased proliferation of cancer cells. The clinical significance of Ep-ICD in human tumors remains an enigma. EpEx, Ep-ICD and β-catenin immunohistochemistry using specific antibodies was conducted on 58 archived thyroid cancer (TC) tissue blocks from 34 patients and correlated with survival analysis of these patients for up to 17 years. The anaplastic (ATC) and aggressive thyroid cancers showed loss of EpEx and increased nuclear and cytoplasmic accumulation of Ep-ICD. In contrast, the low grade papillary thyroid cancers (PTC) showed membranous EpEx and no detectable nuclear Ep-ICD. The ATC also showed concomitant nuclear expression of Ep-ICD and β-catenin. Kaplan-Meier Survival analysis revealed reduced overall survival (OS) for TC patients showing nuclear Ep-ICD expression or loss of membranous EpEx (p < 0.0004), median OS = 5 months as compared to 198 months for patients who did not show nuclear Ep-ICD or demonstrated only membranous EpE. We report reciprocal loss of membrane EpEx but increased nuclear and cytoplasmic accumulation of Ep-ICD in aggressive TC; nuclear Ep-ICD correlated with poor OS of TC patients. Thus nuclear Ep-ICD localization may serve as a useful biomarker for aggressive TC and may represent a novel diagnostic, prognostic and therapeutic target for aggressive TC

  1. Amplification and high-level expression of heat shock protein 90 marks aggressive phenotypes of human epidermal growth factor receptor 2 negative breast cancer.

    Science.gov (United States)

    Cheng, Qing; Chang, Jeffrey T; Geradts, Joseph; Neckers, Leonard M; Haystead, Timothy; Spector, Neil L; Lyerly, H Kim

    2012-04-17

    Although human epidermal growth factor receptor 2 (HER2) positive or estrogen receptor (ER) positive breast cancers are treated with clinically validated anti-HER2 or anti-estrogen therapies, intrinsic and acquired resistance to these therapies appears in a substantial proportion of breast cancer patients and new therapies are needed. Identification of additional molecular factors, especially those characterized by aggressive behavior and poor prognosis, could prioritize interventional opportunities to improve the diagnosis and treatment of breast cancer. We compiled a collection of 4,010 breast tumor gene expression data derived from 23 datasets that have been posted on the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. We performed a genome-scale survival analysis using Cox-regression survival analyses, and validated using Kaplan-Meier Estimates survival and Cox Proportional-Hazards Regression survival analyses. We conducted a genome-scale analysis of chromosome alteration using 481 breast cancer samples obtained from The Cancer Genome Atlas (TCGA), from which combined expression and copy number data were available. We assessed the correlation between somatic copy number alterations and gene expression using analysis of variance (ANOVA). Increased expression of each of the heat shock protein (HSP) 90 isoforms, as well as HSP transcriptional factor 1 (HSF1), was correlated with poor prognosis in different subtypes of breast cancer. High-level expression of HSP90AA1 and HSP90AB1, two cytoplasmic HSP90 isoforms, was driven by chromosome coding region amplifications and were independent factors that led to death from breast cancer among patients with triple-negative (TNBC) and HER2-/ER+ subtypes, respectively. Furthermore, amplification of HSF1 was correlated with higher HSP90AA1 and HSP90AB1 mRNA expression among the breast cancer cells without amplifications of these two genes. A collection of HSP90AA1, HSP90AB1 and HSF

  2. Non-invasive estimation of prostate cancer aggressiveness using diffusion-weighted MRI and 3D proton MR spectroscopy at 3.0 T.

    Science.gov (United States)

    Thörmer, Gregor; Otto, Josephin; Horn, Lars-Christian; Garnov, Nikita; Do, Minh; Franz, Toni; Stolzenburg, Jens-Uwe; Moche, Michael; Kahn, Thomas; Busse, Harald

    2015-01-01

    Clinical management of prostate cancer increasingly aims to distinguish aggressive types that require immediate and radical treatment from indolent tumors that are candidates for watchful waiting. This requires reliable and reproducible parameters to effectively control potential cancer progression. Magnetic resonance imaging (MRI) may provide a non-invasive means for this purpose. To assess the value of diffusion-weighted imaging and proton MR spectroscopy for the prediction of prostate cancer (PCa) aggressiveness. In 39 of 64 consecutive patients who underwent endorectal 3-T MRI prior to radical prostatectomy, prostate specimens were analyzed as whole-mount step sections. Apparent diffusion coefficient (ADC), normalized ADC (nADC: tumor/healthy tissue), choline/citrate (CC), and (choline + creatine)/citrate (CCC) ratios were correlated with Gleason scores (GS) from histopathological results. The power to discriminate low (GS ≤ 6) from higher-risk (GS ≥ 7) tumors was assessed with receiver operating characteristics (area under the curve [AUC]). Resulting threshold values were used by a blinded reader to distinguish between aggressive and indolent tumors. Ninety lesions (1 × GS = 5, 41 × GS = 6, 36 × GS = 7, 12 × GS = 8) were considered. nADC (AUC = 0.90) showed a higher discriminatory power than ADC (AUC = 0.79). AUC for CC and CCC were 0.73 and 0.82, respectively. Using either nADC  1.3, as well as both criteria for aggressive PCa, the reader correctly identified aggressive and indolent tumors in 31 (79%), 28 (72%), and 33 of 39 patients (85%), respectively. Predictions of tumor aggressiveness from TRUS-guided biopsies were correct in 27 of 36 patients (75%). The combination of a highly sensitive normalized ADC with a highly specific CCC was found to be well suited to prospectively estimate PCa aggressiveness with a similar diagnostic accuracy as biopsy results. © The Foundation Acta Radiologica

  3. Higher serum concentrations of vimentin and DAKP1 are associated with aggressive breast tumour phenotypes in Ghanaian women

    NARCIS (Netherlands)

    Arko-Boham, Benjamin; Lomotey, Justice Tanihu; Tetteh, Emmanuel Nomo; Tagoe, Emmanuel Ayitey; Aryee, Nii Ayite; Owusu, Ewurama Ampadu; Okai, Isaac; Blay, Richard Michael; Clegg-Lamptey, Joe-Nat

    2017-01-01

    Breast cancer, the most commonly diagnosed cancer among women and leading cause of cancer-related deaths worldwide, exhibits aggressive behavior in indigenous African women evidenced by high histologic grade tumours with low hormone receptor positivity. Aggressive breast cancers grow quickly, easily

  4. Polymorphisms in the AR and PSA genes as markers of susceptibility and aggressiveness in prostate cancer

    DEFF Research Database (Denmark)

    Kuasne, Hellen; Rodrigues, Iara Sant'Ana; Fuganti, Paulo Emílio

    2010-01-01

    The study of genes involved in androgen pathway can contribute to a better knowledge of prostate cancer. Our aim was to examine if polymorphisms in prostate-specific antigen (PSA) and androgen receptor (AR) genes were involved in prostate cancer risk and aggressiveness. Genotypes were determined...... by PCR-RFLP (PSA) or using a 377 ABI DNA Sequencer (AR). PSA(G/G) genotype (OR = 1.78, 95% CI = 1.06–2.99) and AR short CAG repeats (OR = 1.89, 95% CI = 1.21–2.96) increased risk for prostate cancer and were related with tumor aggressiveness. About 38.3% of tumors showed microsatellite instability....... In conclusion, polymorphisms in these genes may be indicated as potential biomarkers for prostate cancer....

  5. Contrast-Enhanced Harmonic Ultrasonography for the Assessment of Prostate Cancer Aggressiveness: a Preliminary Study

    International Nuclear Information System (INIS)

    Zhu, Yunkai; Chen, Yaqing; Jiang, Jun; Wang, Ren; Zhou, Yongchang; Zhang, Huizhen

    2010-01-01

    To determine whether contrast-enhanced harmonic ultrasonography can be used to predict the aggressiveness of prostate cancer. Contrast-enhanced harmonic ultrasonography was performed in 103 patients suspected of prostate cancer before biopsy. Time intensity curves were reconstructed for systematic biopsy sites and sonographic abnormalities. The characteristics of the curves were described using hemodynamic indices including arrival time (AT), time-to-peak (TTP), and peak intensity (PI). The differences of hemodynamic indices between high-grade and low-grade cancer were analyzed and the correlations between the hemodynamic indices and biopsy Gleason score were studied. Prostate cancer was detected in 41 of 103 patients and there were significant differences in the hemodynamic indices between the biopsy sites of the non-malignant patients and prostate cancer lesions (p < 0.05). The prostate biopsies revealed 154 prostate cancer lesions, including 31 low-grade lesions and 123 high-grade lesions. The hemodynamic indices AT and TTP of highgrade tumors were significantly shorter than those of low-grade tumors (p = 0.001, 0.002). In addition, high-grade peripheral zone (PZ) tumors had higher PI than low-grade PZ tumors (p = 0.009). The PZ prostate cancer Gleason score correlated with PI, AT and TTP, with Spearman correlation coefficients of 0.223, -0.335, and -0.351, respectively (p = 0.013, < 0.001 and < 0.001). Contrast-enhanced ultrasound measurements of hemodynamic indices correlate with the prostate cancer Gleason score

  6. Preferences for active and aggressive intervention among patients with advanced cancer

    Directory of Open Access Journals (Sweden)

    Ennis Marguerite

    2010-10-01

    Full Text Available Abstract Background Intrinsic to "Patient-Centered Care" is being respectful and responsive to individual patient preferences, expressed needs, and personal values. Establishing a patient's preferences for active and aggressive intervention is imperative and foundational to the development of advance care planning. With the increasing awareness and acceptance of palliative philosophies of care, patients with advanced cancer are increasingly transitioning from active and aggressive medical management (AAMM to conservative palliative management (CPM. Methods A cross-sectional study based on a prospective and sequential case series of patients referred to a regional palliative medicine consultative program was assembled between May 1, 2005 and June 30, 2006. Patients and/or their substitute decision makers (SDM completed a questionnaire, at baseline, that assessed their preferences for AAMM en route to their eventual deaths. Seven common interventions constituting AAMM were surveyed: cardiopulmonary resuscitation (CPR & mechanical ventilation (MV, chemotherapy, antibiotics, anticoagulants, blood transfusions, feeding tubes, and artificial hydration. Multivariable analyses were conducted on the seven interventions individually as well as on the composite score that summed preferences for the seven interventions. Results 380 patients with advanced cancer agreed to participate in the study. A trend to desire a mostly conservative palliative approach was noted as 42% of patients desired one or fewer interventions. At baseline, most patients and their SDM's were relatively secure about decisions pertaining to the seven interventions as the rates of being "undecided" ranged from a high of 23.4% for chemotherapy to a low of 3.9% for feeding tubes. Multivariable modeling showed that more AAMM was preferred by younger patients (P Conclusions Although the majority of patients with advanced cancer in this study expressed preferences for CPM, younger age

  7. Non-Steroidal Anti-Inflammatory Drugs, Variation in Inflammatory Genes, and Aggressive Prostate Cancer

    Directory of Open Access Journals (Sweden)

    John S. Witte

    2010-10-01

    Full Text Available Increasing evidence suggests that prostatic inflammation plays a key role in the development of prostate cancer. It remains controversial whether non-steroidal anti-inflammatory drugs (NSAIDs reduce the risk of prostate cancer. Here, we investigate how a previously reported inverse association between NSAID use and the risk of aggressive prostate cancer is modulated by variants in several inflammatory genes. We found that NSAIDs may have differential effects on prostate cancer development, depending on one’s genetic makeup. Further study of these inflammatory pathways may clarify the mechanisms through which NSAIDs impact prostate cancer risk.

  8. Ceramide species are elevated in human breast cancer and are associated with less aggressiveness

    Science.gov (United States)

    Moro, Kazuki; Kawaguchi, Tsutomu; Tsuchida, Junko; Gabriel, Emmanuel; Qi, Qianya; Yan, Li; Wakai, Toshifumi; Takabe, Kazuaki; Nagahashi, Masayuki

    2018-01-01

    Sphingolipids have emerged as key regulatory molecules in cancer cell survival and death. Although important roles of sphingolipids in breast cancer progression have been reported in experimental models, their roles in human patients are yet to be revealed. The aim of this study was to investigate the ceramide levels and its biosynthesis pathways in human breast cancer patients. Breast cancer, peri-tumor and normal breast tissue samples were collected from surgical specimens from a series of 44 patients with breast cancer. The amount of sphingolipid metabolites in the tissue were determined by mass spectrometry. The Cancer Genome Atlas was used to analyze gene expression related to the sphingolipid metabolism. Ceramide levels were higher in breast cancer tissue compared to both normal and peri-tumor breast tissue. Substrates and enzymes that generate ceramide were significantly increased in all three ceramide biosynthesis pathways in cancer. Further, higher levels of ceramide in breast cancer were associated with less aggressive cancer biology presented by Ki-67 index and nuclear grade of the cancer. Interestingly, patients with higher gene expressions of enzymes in the three major ceramide synthesis pathways showed significantly worse prognosis. This is the first study to reveal the clinical relevance of ceramide metabolism in breast cancer patients. We demonstrated that ceramide levels in breast cancer tissue were significantly higher than those in normal tissue, with activation of the three ceramide biosynthesis pathways. We also identified that ceramide levels have a significant association with aggressive phenotype and its enzymes have prognostic impact on breast cancer patients. PMID:29731990

  9. Association between Plasma 25-Hydroxyvitamin D, Ancestry and Aggressive Prostate Cancer among African Americans and European Americans in PCaP

    Science.gov (United States)

    Steck, Susan E.; Arab, Lenore; Zhang, Hongmei; Bensen, Jeannette T.; Fontham, Elizabeth T. H.; Johnson, Candace S.; Mohler, James L.; Smith, Gary J.; Su, Joseph L.; Trump, Donald L.; Woloszynska-Read, Anna

    2015-01-01

    Background African Americans (AAs) have lower circulating 25-hydroxyvitamin D3 [25(OH)D3] concentrations and higher prostate cancer (CaP) aggressiveness than other racial/ethnic groups. The purpose of the current study was to examine the relationship between plasma 25(OH)D3, African ancestry and CaP aggressiveness among AAs and European Americans (EAs). Methods Plasma 25(OH)D3 was measured using LC-MS/MS (Liquid Chromatography Tandem Mass Spectrometry) in 537 AA and 663 EA newly-diagnosed CaP patients from the North Carolina-Louisiana Prostate Cancer Project (PCaP) classified as having either ‘high’ or ‘low’ aggressive disease based on clinical stage, Gleason grade and prostate specific antigen at diagnosis. Mean plasma 25(OH)D3 concentrations were compared by proportion of African ancestry. Logistic regression was used to calculate multivariable adjusted odds ratios (OR) and 95% confidence intervals (95%CI) for high aggressive CaP by tertile of plasma 25(OH)D3. Results AAs with highest percent African ancestry (>95%) had the lowest mean plasma 25(OH)D3 concentrations. Overall, plasma 25(OH)D3 was associated positively with aggressiveness among AA men, an association that was modified by calcium intake (ORT3vs.T1: 2.23, 95%CI: 1.26–3.95 among men with low calcium intake, and ORT3vs.T1: 0.19, 95%CI: 0.05–0.70 among men with high calcium intake). Among EAs, the point estimates of the ORs were <1.0 for the upper tertiles with CIs that included the null. Conclusions Among AAs, plasma 25(OH)D3 was associated positively with CaP aggressiveness among men with low calcium intake and inversely among men with high calcium intake. The clinical significance of circulating concentrations of 25(OH)D3 and interactions with calcium intake in the AA population warrants further study. PMID:25919866

  10. Expression and/or activity of the SVCT2 ascorbate transporter may be decreased in many aggressive cancers, suggesting potential utility for sodium bicarbonate and dehydroascorbic acid in cancer therapy.

    Science.gov (United States)

    McCarty, Mark F

    2013-10-01

    Hypoxia-inducible factor-1 (HIF-1) is a heterodimer transcription factor whose elevated activity in many cancers helps them to survive under hypoxic conditions and enhances their capacity to grow invasively, establish metastases, and survive chemo- or radiotherapy. Optimal intracellular levels of ascorbate suppress the level and transcriptional activity of HIF-1under normoxic or mildly hypoxic conditions by supporting the activity of proly and asparagyl hydroxylases that target HIF-1alpha. High intracellular ascorbate can also work in various ways to down-regulate activation of NF-kappaB which, like HIF-1 is constitutively active in many cancers and promotes aggressive behavior - in part by promoting transcription of HIF-1alpha. Yet recent evidence suggests that, even in the context of adequate ascorbate nutrition, the intracellular ascorbate content of many aggressive cancers may be supoptimal for effective HIF-1 control. This likely reflects low expression or activity of the SVCT2 ascorbate transporter. The expression of SVCT2 in cancers has so far received little study; but the extracellular acidity characteristic of many tumors would be expected to reduce the activity of this transporter, which has a mildly alkaline pH optimum. Unfortunately, since SVCT2 has a high affinity for ascorbate, and its activity is nearly saturated at normal healthy serum levels of this vitamin, increased oral administration of ascorbate would be unlikely to have much impact on the intracellular ascorbate content of tumors. However, cancers in which HIF-1 is active express high levels of glucose transporters such as GLUT-1, and these transporters can promote influx of dehydroascorbic acid (DHA) via facilitated diffusion; once inside the cell, DHA is rapidly reduced to ascorbate, which effectively is "trapped" within the cell. Hence, episodic intravenous infusions of modest doses of DHA may have potential for optimizing the intracellular ascorbate content of cancers, potentially

  11. Fluorescence-guided surgery of a highly-metastatic variant of human triple-negative breast cancer targeted with a cancer-specific GFP adenovirus prevents recurrence

    Science.gov (United States)

    Yano, Shuya; Takehara, Kiyoto; Miwa, Shinji; Kishimoto, Hiroyuki; Tazawa, Hiroshi; Urata, Yasuo; Kagawa, Shunsuke; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M.

    2016-01-01

    We have previously developed a genetically-engineered GFP-expressing telomerase-dependent adenovirus, OBP-401, which can selectively illuminate cancer cells. In the present report, we demonstrate that targeting a triple-negative high-invasive human breast cancer, orthotopically-growing in nude mice, with OBP-401 enables curative fluorescence-guided surgery (FGS). OBP-401 enabled complete resection and prevented local recurrence and greatly inhibited lymph-node metastasis due to the ability of the virus to selectively label and subsequently kill cancer cells. In contrast, residual breast cancer cells become more aggressive after bright (white)-light surgery (BLS). OBP-401-based FGS also improved the overall survival compared with conventional BLS. Thus, metastasis from a highly-aggressive triple-negative breast cancer can be prevented by FGS in a clinically-relevant mouse model. PMID:27689331

  12. Group Music Intervention Reduces Aggression and Improves Self-esteem in Children with Highly Aggressive Behavior: A Pilot Controlled Trial

    Science.gov (United States)

    Lee, Myeong Soo; Lee, Jung-Sook

    2010-01-01

    We investigated the effects of group music intervention on aggression and self-esteem in children with highly aggressive behavior. Forty-eight children were allocated to either a music intervention group or an untreated control group. The music intervention group received 50 min of music intervention twice weekly for 15 consecutive weeks. The outcome measures were Child Behavior Checklist Aggression Problems Scale (Parents), Child Aggression Assessment Inventory (Teachers) and Rosenberg Self-esteem Scale. After 15 weeks, the music intervention group showed significant reduction of aggression and improvement of self-esteem compared with the control group. All outcome measures were significantly lower in the music intervention group than prior to treatment, while there was no change in the control group. These findings suggest that music can reduce aggressive behavior and improve self-esteem in children with highly aggressive behavior. Music intervention is an easily accessible therapy for children and as such may be an effective intervention for aggressive behavior. Further more, objective and replicable measures are required from a randomized controlled trial with a larger sample size and active comparable control. PMID:18955314

  13. Group Music Intervention Reduces Aggression and Improves Self-Esteem in Children with Highly Aggressive Behavior: A Pilot Controlled Trial

    Directory of Open Access Journals (Sweden)

    Ae-Na Choi

    2010-01-01

    Full Text Available We investigated the effects of group music intervention on aggression and self-esteem in children with highly aggressive behavior. Forty-eight children were allocated to either a music intervention group or an untreated control group. The music intervention group received 50 min of music intervention twice weekly for 15 consecutive weeks. The outcome measures were Child Behavior Checklist Aggression Problems Scale (Parents, Child Aggression Assessment Inventory (Teachers and Rosenberg Self-esteem Scale. After 15 weeks, the music intervention group showed significant reduction of aggression and improvement of self-esteem compared with the control group. All outcome measures were significantly lower in the music intervention group than prior to treatment, while there was no change in the control group. These findings suggest that music can reduce aggressive behavior and improve self-esteem in children with highly aggressive behavior. Music intervention is an easily accessible therapy for children and as such may be an effective intervention for aggressive behavior. Further more, objective and replicable measures are required from a randomized controlled trial with a larger sample size and active comparable control.

  14. The role of F18-FDG PET scans in predicting micropapillary thyroid cancer aggressiveness

    International Nuclear Information System (INIS)

    Cho, E. H.; Cho, H. J.; Kim, T. S.; Kang, W. J.; Yun, M. J.; Lee, J. D.

    2007-01-01

    The purpose is to evaluate F18-FDG PET in predicting micropapillary thyroid cancer aggressiveness. 41 patients (38 female, mean age 50y) who had PET before total thyroidectomy between 2002.1∼2007.8 were reviewed. Patients with thyroiditis and multiple nodules were excluded. Thyroid nodules were visually analyzed into groups with increased and no FDG uptake. Peak SUV ratio of liver-to-nodule (pSUV ratio) was taken. pSUV ratio was correlated with nodule size and micropapillary cancer aggressiveness. Perithyroid extension and/or LN metastasis was used as an indicator of micropapillary cancer aggressiveness 20 patients had 0.89 and nodules with increased FDG uptake, with an average pSUV ratio of 1.67 0.15. 21 patients had nodules that were not visible, average size of 0.66 cm 0.24. FDG uptake and nodule size correlation was with an average size of 0.52 cm significant (p=0.051). The nodules were divided into two groups using a cut-off value of pSUV ratio of 0.9. 19 patients had nodules with a pSUV ratio of 0.9 or higher, and 15 of the 19 patients had perithyroid extension and/or LN metastasis. 22 patients had nodules with pSUV ratio lower than 0.9 and 7 of these patients had perithyroid extension and/or LN metastasis. Patients with higher pSUV ratio showed more perithyroid extension or LN metastasis than those with lower pSUV ratio (p=0.01). A total of 8 patients had LN metastasis, but none were visualized on PET. Higher FDG uptake seems to be significantly correlated with tumor aggressiveness in micropapillary thyroid carcinomas. But FDG uptakes in primary tumors were also correlated with tumor size. In other words, larger nodules tend to show aggressive behavior in micropapillary thyroid carcinomas and FDG it self may not be an independent factor for tumor aggressiveness. Also, PET shows an extremely poor sensitivity for the detection of LN metastasis. Therefore, PET may not have any role in the evaluation of patients with micropapillary thyroid carcinomas

  15. The role of F18-FDG PET scans in predicting micropapillary thyroid cancer aggressiveness

    Energy Technology Data Exchange (ETDEWEB)

    Cho, E. H.; Cho, H. J.; Kim, T. S.; Kang, W. J.; Yun, M. J.; Lee, J. D. [Severance Hospital, Seoul (Korea, Republic of)

    2007-07-01

    The purpose is to evaluate F18-FDG PET in predicting micropapillary thyroid cancer aggressiveness. 41 patients (38 female, mean age 50y) who had PET before total thyroidectomy between 2002.1{approx}2007.8 were reviewed. Patients with thyroiditis and multiple nodules were excluded. Thyroid nodules were visually analyzed into groups with increased and no FDG uptake. Peak SUV ratio of liver-to-nodule (pSUV ratio) was taken. pSUV ratio was correlated with nodule size and micropapillary cancer aggressiveness. Perithyroid extension and/or LN metastasis was used as an indicator of micropapillary cancer aggressiveness 20 patients had 0.89 and nodules with increased FDG uptake, with an average pSUV ratio of 1.67 0.15. 21 patients had nodules that were not visible, average size of 0.66 cm 0.24. FDG uptake and nodule size correlation was with an average size of 0.52 cm significant (p=0.051). The nodules were divided into two groups using a cut-off value of pSUV ratio of 0.9. 19 patients had nodules with a pSUV ratio of 0.9 or higher, and 15 of the 19 patients had perithyroid extension and/or LN metastasis. 22 patients had nodules with pSUV ratio lower than 0.9 and 7 of these patients had perithyroid extension and/or LN metastasis. Patients with higher pSUV ratio showed more perithyroid extension or LN metastasis than those with lower pSUV ratio (p=0.01). A total of 8 patients had LN metastasis, but none were visualized on PET. Higher FDG uptake seems to be significantly correlated with tumor aggressiveness in micropapillary thyroid carcinomas. But FDG uptakes in primary tumors were also correlated with tumor size. In other words, larger nodules tend to show aggressive behavior in micropapillary thyroid carcinomas and FDG it self may not be an independent factor for tumor aggressiveness. Also, PET shows an extremely poor sensitivity for the detection of LN metastasis. Therefore, PET may not have any role in the evaluation of patients with micropapillary thyroid carcinomas.

  16. Tumor necrosis is an important hallmark of aggressive endometrial cancer and associates with hypoxia, angiogenesis and inflammation responses.

    Science.gov (United States)

    Bredholt, Geir; Mannelqvist, Monica; Stefansson, Ingunn M; Birkeland, Even; Bø, Trond Hellem; Øyan, Anne M; Trovik, Jone; Kalland, Karl-Henning; Jonassen, Inge; Salvesen, Helga B; Wik, Elisabeth; Akslen, Lars A

    2015-11-24

    Tumor necrosis is associated with aggressive features of endometrial cancer and poor prognosis. Here, we investigated gene expression patterns and potential treatment targets related to presence of tumor necrosis in primary endometrial cancer lesions. By DNA microarray analysis, expression of genes related to tumor necrosis reflected multiple tumor-microenvironment interactions like tissue hypoxia, angiogenesis and inflammation pathways. A tumor necrosis signature of 38 genes and a related patient cluster (Cluster I, 67% of the cases) were associated with features of aggressive tumors such as type II cancers, estrogen receptor negative tumors and vascular invasion. Further, the tumor necrosis signature was increased in tumor cells grown in hypoxic conditions in vitro. Multiple genes with increased expression are known to be activated by HIF1A and NF-kB. Our findings indicate that the presence of tumor necrosis within primary tumors is associated with hypoxia, angiogenesis and inflammation responses. HIF1A, NF-kB and PI3K/mTOR might be potential treatment targets in aggressive endometrial cancers with presence of tumor necrosis.

  17. Maladaptive Personality and Neuropsychological Features of Highly Relationally Aggressive Adolescent Girls

    Directory of Open Access Journals (Sweden)

    Michael Savage

    2017-07-01

    Full Text Available The maladaptive personality and neuropsychological features of highly relationally aggressive females were examined in a group of 30 grade 6, 7, and 8 girls and group-matched controls. Employing a multistage cluster sampling procedure a group of highly, yet almost exclusively, relationally aggressive females were identified and matched on a number of variables to a group of nonaggressive females. Parents of the students in both groups completed the Coolidge Personality and Neuropsychological Inventory, a 200-item DSM-IV-TR aligned, parent-as-respondent, standardized measure of children’s psychological functioning. It was found that high levels of relational aggression, in the absence of physical and verbal aggression, were associated with symptoms of DSM-IV-TR Axis I oppositional defiant disorder and conduct disorder. The highly relationally aggressive group also exhibited a wide variety of personality traits associated with DSM-IV-TR Axis II paranoid, borderline, narcissistic, histrionic, schizotypal, and passive aggressive personality disorders that were not exhibited by the matched controls. Implications of these findings are discussed.

  18. Shifted Golgi targeting of glycosyltransferases and α-mannosidase IA from giantin to GM130-GRASP65 results in formation of high mannose N-glycans in aggressive prostate cancer cells.

    Science.gov (United States)

    Bhat, Ganapati; Hothpet, Vishwanath-Reddy; Lin, Ming-Fong; Cheng, Pi-Wan

    2017-11-01

    There is a pressing need for biomarkers that can distinguish indolent from aggressive prostate cancer to prevent over-treatment of patients with indolent tumor. Golgi targeting of glycosyltransferases was characterized by confocal microscopy after knockdown of GM130, giantin, or both. N-glycans on a trans-Golgi enzyme β4galactosyltransferase-1 isolated by immunoprecipitation from androgen-sensitive and independent prostate cancer cells were determined by matrix-assisted laser desorption-time of flight-mass spectrometry. In situ proximity ligation assay was employed to determine co-localization of (a) α-mannosidase IA, an enzyme required for processing Man 8 GlcNAc 2 down to Man 5 GlcNAc 2 to enable synthesis of complex-type N-glycans, with giantin, GM130, and GRASP65, and (b) trans-Golgi glycosyltransferases with high mannose N-glycans terminated with α3-mannose. Defective giantin in androgen-independent prostate cancer cells results in a shift of Golgi targeting of glycosyltransferases and α-mannosidase IA from giantin to GM130-GRASP65. Consequently, trans-Golgi enzymes and cell surface glycoproteins acquire high mannose N-glycans, which are absent in cells with functional giantin. In situ proximity ligation assays of co-localization of α-mannosidase IA with GM130 and GRASP65, and trans-Golgi glycosyltransferases with high mannose N-glycans are negative in androgen-sensitive LNCaP C-33 cells but positive in androgen-independent LNCaP C-81 and DU145 cells, and LNCaP C-33 cells devoid of giantin. In situ proximity ligation assays of Golgi localization of α-mannosidase IA at giantin versus GM130-GRASP65 site, and absence or presence of N-glycans terminated with α3-mannose on trans-Golgi glycosyltransferases may be useful for distinguishing indolent from aggressive prostate cancer cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. KIAA0100 Modulates Cancer Cell Aggression Behavior of MDA-MB-231 through Microtubule and Heat Shock Proteins

    Directory of Open Access Journals (Sweden)

    Zhenyu Zhong

    2018-06-01

    Full Text Available The KIAA0100 gene was identified in the human immature myeloid cell line cDNA library. Recent studies have shown that its expression is elevated in breast cancer and associated with more aggressive cancer types as well as poor outcomes. However, its cellular and molecular function is yet to be understood. Here we show that silencing KIAA0100 by siRNA in the breast cancer cell line MDA-MB-231 significantly reduced the cancer cells’ aggressive behavior, including cell aggregation, reattachment, cell metastasis and invasion. Most importantly, silencing the expression of KIAA0100 particularly sensitized the quiescent cancer cells in suspension culture to anoikis. Immunoprecipitation, mass spectrometry and immunofluorescence analysis revealed that KIAA0100 may play multiple roles in the cancer cells, including stabilizing microtubule structure as a microtubule binding protein, and contributing to MDA-MB-231 cells Anoikis resistance by the interaction with stress protein HSPA1A. Our study also implies that the interaction between KIAA0100 and HSPA1A may be targeted for new drug development to specifically induce anoikis cell death in the cancer cell.

  20. Calix[6]arene bypasses human pancreatic cancer aggressiveness: downregulation of receptor tyrosine kinases and induction of cell death by reticulum stress and autophagy.

    Science.gov (United States)

    Pelizzaro-Rocha, Karin Juliane; de Jesus, Marcelo Bispo; Ruela-de-Sousa, Roberta Regina; Nakamura, Celso Vataru; Reis, Fabiano Souza; de Fátima, Angelo; Ferreira-Halder, Carmen Veríssima

    2013-12-01

    Pancreatic cancer ranks fourth among cancer-related causes of death in North America. Minimal progress has been made in the diagnosis and treatment of patients with late-stage tumors. Moreover, pancreatic cancer aggressiveness is closely related to high levels of pro-survival mediators, which can ultimately lead to rapid disease progression, resistance and metastasis. The main goal of this study was to define the mechanisms by which calix[6]arene, but not other calixarenes, efficiently decreases the aggressiveness of a drug resistant human pancreas carcinoma cell line (Panc-1). Calix[6]arene was more potent in reducing Panc-1 cell viability than gemcitabine and 5-fluorouracil. In relation to the underlying mechanisms of cytotoxic effects, it led to cell cycle arrest in the G0/G1 phase through downregulation of PIM1, CDK2, CDK4 and retinoblastoma proteins. Importantly, calix[6]arene abolished signal transduction of Mer and AXL tyrosine kinase receptors, both of which are usually overexpressed in pancreatic cancer. Accordingly, inhibition of PI3K and mTOR was also observed, and these proteins are positively modulated by Mer and AXL. Despite decreasing the phosphorylation of AKT at Thr308, calix[6]arene caused an increase in phosphorylation at Ser473. These findings in conjunction with increased BiP and IRE1-α provide a molecular basis explaining the capacity of calix[6]arene to trigger endoplasmic reticulum stress and autophagic cell death. Our findings highlight calix[6]arene as a potential candidate for overcoming pancreatic cancer aggressiveness. Importantly, we provide evidence that calix[6]arene affects a broad array of key targets that are usually dysfunctional in pancreatic cancer, a highly desirable characteristic for chemotherapeutics. © 2013.

  1. Relationship between male pattern baldness and the risk of aggressive prostate cancer: an analysis of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

    Science.gov (United States)

    Zhou, Cindy Ke; Pfeiffer, Ruth M; Cleary, Sean D; Hoffman, Heather J; Levine, Paul H; Chu, Lisa W; Hsing, Ann W; Cook, Michael B

    2015-02-10

    Male pattern baldness and prostate cancer appear to share common pathophysiologic mechanisms. However, results from previous studies that assess their relationship have been inconsistent. Therefore, we investigated the association of male pattern baldness at age 45 years with risks of overall and subtypes of prostate cancer in a large, prospective cohort—the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. We included 39,070 men from the usual care and screening arms of the trial cohort who had no cancer diagnosis (excluding nonmelanoma skin cancer) at the start of follow-up and recalled their hair-loss patterns at age 45 years. Hazard ratios (HRs) and 95% CIs were estimated by using Cox proportional hazards regression models with age as the time metric. During follow-up (median, 2.78 years), 1,138 incident prostate cancer cases were diagnosed, 571 of which were aggressive (biopsy Gleason score ≥ 7, and/or clinical stage III or greater, and/or fatal). Compared with no baldness, frontal plus moderate vertex baldness at age 45 years was not significantly associated with overall (HR, 1.19; 95% CI, 0.98 to 1.45) or nonaggressive (HR, 0.97; 95% CI, 0.72 to 1.30) prostate cancer risk but was significantly associated with increased risk of aggressive prostate cancer (HR, 1.39; 95% CI, 1.07 to 1.80). Adjustment for covariates did not substantially alter these estimates. Other classes of baldness were not significantly associated with overall or subtypes of prostate cancer. Our analysis indicates that frontal plus moderate vertex baldness at age 45 years is associated with an increased risk of aggressive prostate cancer and supports the possibility of common pathophysiologic mechanisms. © 2014 by American Society of Clinical Oncology.

  2. [Therapeutic Aggressiveness and Liquid Oncology].

    Science.gov (United States)

    Barón Duarte, F J; Rodríguez Calvo, M S; Amor Pan, J R

    2017-01-01

    Aggressiveness criteria proposed in the scientific literature a decade ago provide a quality judgment and are a reference in the care of patients with advanced cancer, but their use is not generalized in the evaluation of Oncology Services. In this paper we analyze the therapeutic aggressiveness, according to standard criteria, in 1.001 patients with advanced cancer who died in our Institution between 2010 and 2013. The results seem to show that aggressiveness at the end of life is present more frequently than experts recommend. About 25% of patients fulfill at least one criterion of aggressiveness. This result could be explained by a liquid Oncology which does not prioritize the patient as a moral subject in the clinical appointment. Medical care is oriented to necessities and must be articulated in a model focused on dignity and communication. Its implementation through Advanced Care Planning, consideration of patient's values and preferences, and Limitation of therapeutic effort are ways to reduce aggressiveness and improve clinical practice at the end of life. We need to encourage synergic and proactive attitudes, adding the best of cancer research with the best clinical care for the benefit of human being, moral subject and main goal of Medicine.

  3. Microenvironment-Centred Dynamics in Aggressive B-Cell Lymphomas

    Directory of Open Access Journals (Sweden)

    Matilde Cacciatore

    2012-01-01

    Full Text Available Aggressive B-cell lymphomas share high proliferative and invasive attitudes and dismal prognosis despite heterogeneous biological features. In the interchained sequence of events leading to cancer progression, neoplastic clone-intrinsic molecular events play a major role. Nevertheless, microenvironment-related cues have progressively come into focus as true determinants for this process. The cancer-associated microenvironment is a complex network of nonneoplastic immune and stromal cells embedded in extracellular components, giving rise to a multifarious crosstalk with neoplastic cells towards the induction of a supportive milieu. The immunological and stromal microenvironments have been classically regarded as essential partners of indolent lymphomas, while considered mainly negligible in the setting of aggressive B-cell lymphomas that, by their nature, are less reliant on external stimuli. By this paper we try to delineate the cardinal microenvironment-centred dynamics exerting an influence over lymphoid clone progression in aggressive B-cell lymphomas.

  4. Update on Anaplastic Thyroid Carcinoma: Morphological, Molecular, and Genetic Features of the Most Aggressive Thyroid Cancer

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    Moira Ragazzi

    2014-01-01

    Full Text Available Anaplastic thyroid carcinoma (ATC is the most aggressive form of thyroid cancer. It shows a wide spectrum of morphological presentations and the diagnosis could be challenging due to its high degree of dedifferentiation. Molecular and genetic features of ATC are widely heterogeneous as well and many efforts have been made to find a common profile in order to clarify its cancerogenetic process. A comprehensive review of the current literature is here performed, focusing on histopathological and genetic features.

  5. Aggressive Students and High School Dropout: An Event History Analysis

    Science.gov (United States)

    Orozco, Steven R.

    2016-01-01

    Aggressive students often struggle in multiple domains of their school functioning and are at increased risk for high school dropout. Research has identified a variety of warning flags which are strong predictors of high school dropout. While it is known that aggressive students exhibit many of these warning flags, there is little research which…

  6. Comparative evaluation of urinary PCA3 and TMPRSS2: ERG scores and serum PHI in predicting prostate cancer aggressiveness.

    Science.gov (United States)

    Tallon, Lucile; Luangphakdy, Devillier; Ruffion, Alain; Colombel, Marc; Devonec, Marian; Champetier, Denis; Paparel, Philippe; Decaussin-Petrucci, Myriam; Perrin, Paul; Vlaeminck-Guillem, Virginie

    2014-07-30

    It has been suggested that urinary PCA3 and TMPRSS2:ERG fusion tests and serum PHI correlate to cancer aggressiveness-related pathological criteria at prostatectomy. To evaluate and compare their ability in predicting prostate cancer aggressiveness, PHI and urinary PCA3 and TMPRSS2:ERG (T2) scores were assessed in 154 patients who underwent radical prostatectomy for biopsy-proven prostate cancer. Univariate and multivariate analyses using logistic regression and decision curve analyses were performed. All three markers were predictors of a tumor volume≥0.5 mL. Only PHI predicted Gleason score≥7. T2 score and PHI were both independent predictors of extracapsular extension(≥pT3), while multifocality was only predicted by PCA3 score. Moreover, when compared to a base model (age, digital rectal examination, serum PSA, and Gleason sum at biopsy), the addition of both PCA3 score and PHI to the base model induced a significant increase (+12%) when predicting tumor volume>0.5 mL. PHI and urinary PCA3 and T2 scores can be considered as complementary predictors of cancer aggressiveness at prostatectomy.

  7. Comparative Evaluation of Urinary PCA3 and TMPRSS2: ERG Scores and Serum PHI in Predicting Prostate Cancer Aggressiveness

    Directory of Open Access Journals (Sweden)

    Lucile Tallon

    2014-07-01

    Full Text Available It has been suggested that urinary PCA3 and TMPRSS2:ERG fusion tests and serum PHI correlate to cancer aggressiveness-related pathological criteria at prostatectomy. To evaluate and compare their ability in predicting prostate cancer aggressiveness, PHI and urinary PCA3 and TMPRSS2:ERG (T2 scores were assessed in 154 patients who underwent radical prostatectomy for biopsy-proven prostate cancer. Univariate and multivariate analyses using logistic regression and decision curve analyses were performed. All three markers were predictors of a tumor volume ≥0.5 mL. Only PHI predicted Gleason score ≥7. T2 score and PHI were both independent predictors of extracapsular extension (≥pT3, while multifocality was only predicted by PCA3 score. Moreover, when compared to a base model (age, digital rectal examination, serum PSA, and Gleason sum at biopsy, the addition of both PCA3 score and PHI to the base model induced a significant increase (+12% when predicting tumor volume >0.5 mL. PHI and urinary PCA3 and T2 scores can be considered as complementary predictors of cancer aggressiveness at prostatectomy.

  8. Cytokeratin 19 (KRT19) has a Role in the Reprogramming of Cancer Stem Cell-Like Cells to Less Aggressive and More Drug-Sensitive Cells

    Science.gov (United States)

    Kim, Kyeongseok; Yang, Gwang-Mo; Choi, Hye Yeon

    2018-01-01

    Cytokeratin 19 (KRT19) is a cytoplasmic intermediate filament protein, which is responsible for structural rigidity and multipurpose scaffolds. In several cancers, KRT19 is overexpressed and may play a crucial role in tumorigenic transformation. In our previous study, we revealed the role of KRT19 as signaling component which mediated Wnt/NOTCH crosstalk through NUMB transcription in breast cancer. Here, we investigated the function of KRT19 in cancer reprogramming and drug resistance in breast cancer cells. We found that expression of KRT19 was attenuated in several patients-derived breast cancer tissues and patients with a low expression of KRT19 were significantly correlated with poor prognosis in breast cancer patients. Consistently, highly aggressive and drug-resistant breast cancer patient-derived cancer stem cell-like cells (konkuk university-cancer stem cell-like cell (KU-CSLCs)) displayed higher expression of cancer stem cell (CSC) markers, including ALDH1, CXCR4, and CD133, but a much lower expression of KRT19 than that is seen in highly aggressive triple negative breast cancer MDA-MB231 cells. Moreover, we revealed that the knockdown of KRT19 in MDA-MB231 cells led to an enhancement of cancer properties, such as cell proliferation, sphere formation, migration, and drug resistance, while the overexpression of KRT19 in KU-CSLCs resulted in the significant attenuation of cancer properties. KRT19 regulated cancer stem cell reprogramming by modulating the expression of cancer stem cell markers (ALDH1, CXCR4, and CD133), as well as the phosphorylation of Src and GSK3β (Tyr216). Therefore, our data may imply that the modulation of KRT19 expression could be involved in cancer stem cell reprogramming and drug sensitivity, which might have clinical implications for cancer or cancer stem cell treatment. PMID:29747452

  9. Cytokeratin 19 (KRT19) has a Role in the Reprogramming of Cancer Stem Cell-Like Cells to Less Aggressive and More Drug-Sensitive Cells.

    Science.gov (United States)

    Saha, Subbroto Kumar; Kim, Kyeongseok; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

    2018-05-09

    Cytokeratin 19 ( KRT19 ) is a cytoplasmic intermediate filament protein, which is responsible for structural rigidity and multipurpose scaffolds. In several cancers, KRT19 is overexpressed and may play a crucial role in tumorigenic transformation. In our previous study, we revealed the role of KRT19 as signaling component which mediated Wnt/NOTCH crosstalk through NUMB transcription in breast cancer. Here, we investigated the function of KRT19 in cancer reprogramming and drug resistance in breast cancer cells. We found that expression of KRT19 was attenuated in several patients-derived breast cancer tissues and patients with a low expression of KRT19 were significantly correlated with poor prognosis in breast cancer patients. Consistently, highly aggressive and drug-resistant breast cancer patient-derived cancer stem cell-like cells (konkuk university-cancer stem cell-like cell (KU-CSLCs)) displayed higher expression of cancer stem cell (CSC) markers, including ALDH1 , CXCR4 , and CD133 , but a much lower expression of KRT19 than that is seen in highly aggressive triple negative breast cancer MDA-MB231 cells. Moreover, we revealed that the knockdown of KRT19 in MDA-MB231 cells led to an enhancement of cancer properties, such as cell proliferation, sphere formation, migration, and drug resistance, while the overexpression of KRT19 in KU-CSLCs resulted in the significant attenuation of cancer properties. KRT19 regulated cancer stem cell reprogramming by modulating the expression of cancer stem cell markers ( ALDH1 , CXCR4 , and CD133 ), as well as the phosphorylation of Src and GSK3β (Tyr216). Therefore, our data may imply that the modulation of KRT19 expression could be involved in cancer stem cell reprogramming and drug sensitivity, which might have clinical implications for cancer or cancer stem cell treatment.

  10. The role of attractiveness and aggression in high school popularity

    NARCIS (Netherlands)

    Borch, C.; Hyde, A.; Cillessen, A.H.N.

    2011-01-01

    This study examines the effects of physical attractiveness and aggression on popularity among high school students. Previous work has found positive relationships between aggression and popularity and physical attractiveness and popularity. The current study goes beyond this work by examining the

  11. VEGFR-1 Overexpression Identifies a Small Subgroup of Aggressive Prostate Cancers in Patients Treated by Prostatectomy

    Directory of Open Access Journals (Sweden)

    Maria Christina Tsourlakis

    2015-04-01

    Full Text Available The VEGFR-1 is suggested to promote tumor progression. In the current study we analyzed prevalence and prognostic impact of the VEGFR-1 by immunohistochemistry on a tissue microarray containing more than 3000 prostate cancer specimens. Results were compared to tumor phenotype, ETS-related gene (ERG status, and biochemical recurrence. Membranous VEGFR-1 expression was detectable in 32.6% of 2669 interpretable cancers and considered strong in 1.7%, moderate in 6.7% and weak in 24.2% of cases. Strong VEGFR-1 expression was associated with TMPRSS2:ERG fusion status as determined by fluorescence in situ hybridization (FISH and immunohistochemistry (p < 0.0001 each. Elevated VEGFR-1 expression was linked to high Gleason grade and advanced pT stage in TMPRSS2:ERG negative cancers (p = 0.0008 and p = 0.001, while these associations were absent in TMPRSS2:ERG positive cancers. VEGFR-1 expression was also linked to phosphatase and tensin homolog (PTEN deletions. A comparison with prostate specific antigen (PSA recurrence revealed that the 1.7% of prostate cancers with the highest VEGFR-1 levels had a strikingly unfavorable prognosis. This could be seen in all cancers, in the subsets of TMPRSS2:ERG positive or negative, PTEN deleted or undeleted carcinomas (p < 0.0001 each. High level VEGFR-1 expression is infrequent in prostate cancer, but identifies a subgroup of aggressive cancers, which may be candidates for anti-VEGFR-1 targeted therapy.

  12. Dietary, Supplement, and Adipose Tissue Tocopherols Levels in Relation to Prostate Cancer Aggressiveness Among African and European Americans: The North Carolina-Louisiana Prostate Cancer Project (PCaP)

    Science.gov (United States)

    Antwi, Samuel; Steck, Susan E.; Su, L. Joseph; Hebert, James R.; Zhang, Hongmei; Fontham, Elizabeth T. H.; Smith, Gary; Bensen, Jeannette T.; Mohler, James L.; Arab, Lenore

    2016-01-01

    Background Controversies remain over the safety and efficacy of vitamin E (i.e., α–tocopherol) supplementation use for the prevention of prostate cancer (CaP); however, associations of different tocopherol forms and CaP aggressiveness have yet to be examined. Methods This study examined whether food intake of tocopherols, vitamin E supplement use, and adipose tissue biomarkers of tocopherol were associated with CaP aggressiveness among African-American (AA, n=1,023) and European-American (EA, n=1,079) men diagnosed with incident CaP. Dietary tocopherols were estimated from a food frequency questionnaire, supplement use from questionnaire/inventory, and biomarkers from abdominal adipose samples measured using high-performance liquid chromatography. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated from logistic regression comparing high aggressive CaP to low/intermediate aggressive CaP, adjusting for covariates. Results Dietary intakes of α-and δ-tocopherol were related inversely to CaP aggressiveness among EAs [OR (95% CI), highest versus lowest quartile: α-tocopherol, 0.34 (0.17–0.69), Ptrend = 0.006; δ-tocopherol, 0.45 (0.21–0.95) Ptrend = 0.007]. Inverse associations between dietary and supplemental α-tocopherol and CaP aggressiveness were observed among AAs, though these did not reach statistical significance [OR (95% CI), highest versus lowest quartile: dietary α-tocopherol, 0.58 (0.28–1.19), Ptrend = 0.20; supplemental α-tocopherol, 0.64 (0.31–1.21) Ptrend = 0.15]. No significant association was observed between adipose tocopherol levels and CaP aggressiveness [OR (95% CI), highest versus lowest quartiles of α-tocopherol for EAs 1.43 (0.66–3.11) and AAs 0.66 (0.27–1.62)]. Conclusions The inverse associations observed between dietary sources of tocopherols and CaP aggressiveness suggests a beneficial role of food sources of these tocopherols in CaP aggressiveness. PMID:26053590

  13. Dietary, supplement, and adipose tissue tocopherol levels in relation to prostate cancer aggressiveness among African and European Americans: The North Carolina-Louisiana Prostate Cancer Project (PCaP).

    Science.gov (United States)

    Antwi, Samuel O; Steck, Susan E; Su, L Joseph; Hébert, James R; Zhang, Hongmei; Fontham, Elizabeth T H; Smith, Gary J; Bensen, Jeannette T; Mohler, James L; Arab, Lenore

    2015-09-01

    Controversies remain over the safety and efficacy of vitamin E (i.e., α-tocopherol) supplementation use for the prevention of prostate cancer (CaP); however, associations of different tocopherol forms and CaP aggressiveness have yet to be examined. This study examined whether food intake of tocopherols, vitamin E supplement use, and adipose tissue biomarkers of tocopherol were associated with CaP aggressiveness among African-American (AA, n = 1,023) and European-American (EA, n = 1,079) men diagnosed with incident CaP. Dietary tocopherols were estimated from a food frequency questionnaire, supplement use from questionnaire/inventory, and biomarkers from abdominal adipose samples measured using high-performance liquid chromatography. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were estimated from logistic regression comparing high-aggressive CaP to low/intermediate aggressive CaP, adjusting for covariates. Dietary intakes of α-and δ-tocopherol were related inversely to CaP aggressiveness among EAs [OR (95%CI), highest versus lowest quartile: α-tocopherol, 0.34 (0.17-0.69), P(trend)  = 0.006; δ-tocopherol, 0.45 (0.21-0.95) P(trend)  = 0.007]. Inverse associations between dietary and supplemental α-tocopherol and CaP aggressiveness were observed among AAs, though these did not reach statistical significance [OR (95%CI), highest versus lowest quartile: dietary α-tocopherol, 0.58 (0.28-1.19), P(trend)  = 0.20; supplemental α-tocopherol, 0.64 (0.31-1.21) P(trend)  = 0.15]. No significant association was observed between adipose tocopherol levels and CaP aggressiveness [OR (95%CI), highest versus lowest quartiles of α-tocopherol for EAs 1.43 (0.66-3.11) and AAs 0.66 (0.27-1.62)]. The inverse associations observed between dietary sources of tocopherols and CaP aggressiveness suggests a beneficial role of food sources of these tocopherols in CaP aggressiveness. © 2015 Wiley Periodicals, Inc.

  14. On complexity and homogeneity measures in predicting biological aggressiveness of prostate cancer; Implication of the cellular automata model of tumor growth.

    Science.gov (United States)

    Tanase, Mihai; Waliszewski, Przemyslaw

    2015-12-01

    We propose a novel approach for the quantitative evaluation of aggressiveness in prostate carcinomas. The spatial distribution of cancer cell nuclei was characterized by the global spatial fractal dimensions D0, D1, and D2. Two hundred eighteen prostate carcinomas were stratified into the classes of equivalence using results of ROC analysis. A simulation of the cellular automata mix defined a theoretical frame for a specific geometric representation of the cell nuclei distribution called a local structure correlation diagram (LSCD). The LSCD and dispersion Hd were computed for each carcinoma. Data mining generated some quantitative criteria describing tumor aggressiveness. Alterations in tumor architecture along progression were associated with some changes in both shape and the quantitative characteristics of the LSCD consistent with those in the automata mix model. Low-grade prostate carcinomas with low complexity and very low biological aggressiveness are defined by the condition D0 1.764 and Hd < 38. The novel homogeneity measure Hd identifies carcinomas with very low aggressiveness within the class of complexity C1 or carcinomas with very high aggressiveness in the class C7. © 2015 Wiley Periodicals, Inc.

  15. The Role of Attractiveness and Aggression in High School Popularity

    Science.gov (United States)

    Borch, Casey; Hyde, Allen; Cillessen, Antonius H. N.

    2011-01-01

    This study examines the effects of physical attractiveness and aggression on popularity among high school students. Previous work has found positive relationships between aggression and popularity and physical attractiveness and popularity. The current study goes beyond this work by examining the interactive effects of physical attractiveness and…

  16. Interaction of mammographic breast density with menopausal status and postmenopausal hormone use in relation to the risk of aggressive breast cancer subtypes.

    Science.gov (United States)

    Yaghjyan, Lusine; Tamimi, Rulla M; Bertrand, Kimberly A; Scott, Christopher G; Jensen, Matthew R; Pankratz, V Shane; Brandt, Kathy; Visscher, Daniel; Norman, Aaron; Couch, Fergus; Shepherd, John; Fan, Bo; Chen, Yunn-Yi; Ma, Lin; Beck, Andrew H; Cummings, Steven R; Kerlikowske, Karla; Vachon, Celine M

    2017-09-01

    We examined the associations of mammographic breast density with breast cancer risk by tumor aggressiveness and by menopausal status and current postmenopausal hormone therapy. This study included 2596 invasive breast cancer cases and 4059 controls selected from participants of four nested case-control studies within four established cohorts: the Mayo Mammography Health Study, the Nurses' Health Study, Nurses' Health Study II, and San Francisco Mammography Registry. Percent breast density (PD), absolute dense (DA), and non-dense areas (NDA) were assessed from digitized film-screen mammograms using a computer-assisted threshold technique and standardized across studies. We used polytomous logistic regression to quantify the associations of breast density with breast cancer risk by tumor aggressiveness (defined as presence of at least two of the following tumor characteristics: size ≥2 cm, grade 2/3, ER-negative status, or positive nodes), stratified by menopausal status and current hormone therapy. Overall, the positive association of PD and borderline inverse association of NDA with breast cancer risk was stronger in aggressive vs. non-aggressive tumors (≥51 vs. 11-25% OR 2.50, 95% CI 1.94-3.22 vs. OR 2.03, 95% CI 1.70-2.43, p-heterogeneity = 0.03; NDA 4th vs. 2nd quartile OR 0.54, 95% CI 0.41-0.70 vs. OR 0.71, 95% CI 0.59-0.85, p-heterogeneity = 0.07). However, there were no differences in the association of DA with breast cancer by aggressive status. In the stratified analysis, there was also evidence of a stronger association of PD and NDA with aggressive tumors among postmenopausal women and, in particular, current estrogen+progesterone users (≥51 vs. 11-25% OR 3.24, 95% CI 1.75-6.00 vs. OR 1.93, 95% CI 1.25-2.98, p-heterogeneity = 0.01; NDA 4th vs. 2nd quartile OR 0.43, 95% CI 0.21-0.85 vs. OR 0.56, 95% CI 0.35-0.89, p-heterogeneity = 0.01), even though the interaction was not significant. Our findings suggest that associations of mammographic

  17. Angiosarcoma of penis: Case report of an aggressive penile cancer

    Directory of Open Access Journals (Sweden)

    Vinod Priyadarshi

    2015-01-01

    Full Text Available Angiosarcoma is a very rare mesenchymal tumor of penis. Though extremely unusual, it should be considered in the differential diagnosis in patients presenting with a penile growth or a localized subcutaneous penile lesions as they are very aggressive and there is a high chance of recurrence. One such case is reported here, which was aggressively treated with total penectomy and the patient did not show any recurrence in 2 years of follow-up.

  18. Aggressive approach in a case of cancer cervix with uremia

    Directory of Open Access Journals (Sweden)

    M G Janaki

    2010-01-01

    Full Text Available Carcinoma of cervix is the most common cancer in developing countries. Majority of them present in locally advanced stages. A 36-year-old lady presented with bleeding and white discharge per vagina since four months, vomiting and reduced urine output since two weeks. Patient had an exophytic cervical growth. Investigation revealed elevated serum creatinine. Patient received single fraction radiation and underwent percutaneous nephrostomy. At one month follow-up, serum creatinine returned to almost normal level. Patient underwent bilateral ante grade stenting and completed concurrent chemoradiotherapy. In selected subsets of patients, aggressive management offered longer palliation and good quality of life.

  19. TGF-β regulates DNA methyltransferase expression in prostate cancer, correlates with aggressive capabilities, and predicts disease recurrence.

    Directory of Open Access Journals (Sweden)

    Qiang Zhang

    Full Text Available DNA methyltransferase (DNMT is one of the major factors mediating the methylation of cancer related genes such as TGF-β receptors (TβRs. This in turn may result in a loss of sensitivity to physiologic levels of TGF-β in aggressive prostate cancer (CaP. The specific mechanisms of DNMT's role in CaP remain undetermined. In this study, we describe the mechanism of TGF-β-mediated DNMT in CaP and its association with clinical outcomes following radical prostatectomy.We used human CaP cell lines with varying degrees of invasive capability to describe how TGF-β mediates the expression of DNMT in CaP, and its effects on methylation status of TGF-β receptors and the invasive capability of CaP in vitro and in vivo. Furthermore, we determined the association between DNMT expression and clinical outcome after radical prostatectomy. We found that more aggressive CaP cells had significantly higher TGF-β levels, increased expression of DNMT, but reduced TβRs when compared to benign prostate cells and less aggressive prostate cancer cells. Blockade of TGF-β signaling or ERK activation (p-ERK was associated with a dramatic decrease in the expression of DNMT, which results in a coincident increase in the expression of TβRs. Blockade of either TGF-β signaling or DNMT dramatically decreased the invasive capabilities of CaP. Inhibition of TGF-β in an TRAMP-C2 CaP model in C57BL/6 mice using 1D11 was associated with downregulation of DNMTs and p-ERK and impairment in tumor growth. Finally, independent of Gleason grade, increased DNMT1 expression was associated with biochemical recurrence following surgical treatment for prostate cancer.Our findings demonstrate that CaP derived TGF-β may induce the expression of DNMTs in CaP which is associated with methylation of its receptors and the aggressive potential of CaP. In addition, DNMTs is an independent predictor for disease recurrence after prostatectomy, and may have clinical implications for Ca

  20. Comprehensive Evaluation of the Role of EZH2 in the Growth, Invasion, and Aggression of a Panel of Prostate Cancer Cell Lines

    Science.gov (United States)

    Karanikolas, Breanne D.W.; Figueiredo, Marxa L.; Wu, Lily

    2010-01-01

    Background Although most prostate cancers respond well to initial treatments, a fraction of prostate cancers are more aggressive and will recur and metastasize. At that point, there are few treatment options available. Significant efforts have been made to identify biomarkers that will identify these more aggressive cancers to tailor a more vigorous treatment in order to improve outcome. Polycomb Group protein Enhancer of Zeste 2 (EZH2) was found to be overexpressed in metastatic prostate tumors, and is considered an excellent candidate for such a biomarker. Scattered studies have found that EZH2 overexpression causes neoplastic transformation, invasion, and growth of prostate cells. However, these studies utilized different systems and cell lines, and so are difficult to correlate with one another. Methods In this study, a comprehensive evaluation of the phenotypic effects of EZH2 in a panel of five prostate cancer cell lines was performed. By using multiple cell lines, and examining overexpression and knockdown of EZH2 concurrently, a broad view of EZH2's role in prostate cancer was achieved. Results Overexpression of EZH2 led to more aggressive behaviors in all prostate cell lines tested. In contrast, downregulation of EZH2 reduced invasion and tumorigenicity of androgen-independent cell lines CWR22Rv1, PC3, and DU145, but not of androgen-dependent cell lines LAPC4 and LNCaP. Conclusions Findings from this study suggest androgen-independent prostate tumors are more dependent on EZH2 expression than androgen-dependent tumors. Our observations provide an explanation for the strong correlation between EZH2 overexpression and advanced stage, aggressive prostate cancers. PMID:20087897

  1. Rad51 expression levels predict synthetic lethality and metastatic potential in high grade breast cancers

    International Nuclear Information System (INIS)

    Wiegmans, A.P.; Al-Ejeh, F.; Khanna, K.K.

    2012-01-01

    Among women with breast cancer, 30-40% will develop metastatic disease and only achieve an overall survival of less than 5 years. Despite new-targeted therapy, breast tumors that harbour similar histology or molecular phenotype differ in their response to treatment. To uncover potential new therapeutic targets and improve outcome, we performed data mining of cancer micro array databases. We found that high expression of the homologous recombination protein, RAD51, was significantly associated with high-grade breast cancer, aggressive subtypes and increased risk of metastasis. We confirmed using immunohistochemistry that RAD5 1 was highly expressed in metastatic tumours and high-grade triple negative, HER2+ and luminal-B tumours. This provided a rationale for targeting RAD5 1 in high-grade, therapy-resistant breast cancers. Here, we report for the first time preclinical evaluation of RAD5 1 as a therapeutic target. We found that, in-vitro high RAD5 expressing cell lines were resistant to PARP inhibitor while knockdown reversed this resistance. In-vivo, knockdown of RAD5 1 inhibited metastatic progression using a syngeneic breast cancer model and the seeding of human xenografts to distant sites, including brain and lung. Concurrent PARP inhibition reduced primary tumor growth and delayed metastasis supporting synthetic lethality in-vivo. Together these insights provide pre-clinical data demonstrating RAD5 1 as a new biomarker and potential therapeutic target against aggressive metastatic breast cancer. (author)

  2. Androgen-deprivation therapy-induced aggressive prostate cancer with neuroendocrine differentiation

    Directory of Open Access Journals (Sweden)

    Julia Lipianskaya

    2014-08-01

    Full Text Available Most prostate cancers (PCas are classified as acinar type (conventional adenocarcinoma which are composed of tumor cells with luminal differentiation including the expression of androgen receptor (AR and prostate-specific antigen (PSA. There are also scattered neuroendocrine (NE cells in every case of adenocarcinoma. The NE cells are quiesecent, do not express AR or PSA, and their function remains unclear. We have demonstrated that IL8-CXCR2-P53 pathway provides a growth-inhibitory signal and keeps the NE cells in benign prostate and adenocarcinoma quiescent. Interestingly, some patients with a history of adenocarcinoma recur with small cell neuroendocrine carcinoma (SCNC after hormonal therapy, and such tumors are composed of pure NE cells that are highly proliferative and aggressive, due to P53 mutation and inactivation of the IL8-CXCR2-P53 pathway. The incidence of SCNC will likely increase due to the widespread use of novel drugs that further inhibit AR function or intratumoral androgen synthesis. A phase II trial has demonstrated that platinum-based chemotherapy may be useful for such therapy-induced tumors.

  3. Study in mice shows that an aggressive type of breast cancer is linked to an inflammatory protein

    Science.gov (United States)

    Aberrant expression of an inflammatory protein, nitric oxide synthase 2 (NOS2), may enhance the progression and metastasis of an aggressive and less common form of breast cancer, known as the estrogen receptor-negative type of disease.

  4. Interpatient variation in normal peripheral zone apparent diffusion coefficient: effect on the prediction of prostate cancer aggressiveness

    NARCIS (Netherlands)

    Litjens, G.J.S.; Hambrock, T.; Hulsbergen-van de Kaa, C.A.; Barentsz, J.O.; Huisman, H.J.

    2012-01-01

    Purpose: To determine the interpatient variability of prostate peripheral zone (PZ) apparent diffusion coefficient (ADC) and its effect on the assessment of prostate cancer aggressiveness. Materials and Methods: The requirement for institutional review board approval was waived. Intra- and

  5. Aggression Can be Contagious: Longitudinal Associations between Proactive Aggression and Reactive Aggression Among Young Twins

    Science.gov (United States)

    Dickson, Daniel J.; Richmond, Ashley; Brendgen, Mara; Vitaro, Frank; Laursen, Brett; Dionne, Ginette; Boivin, Michel

    2015-01-01

    The present study examined sibling influence over reactive and proactive aggression in a sample of 452 same-sex twins (113 male dyads, 113 female dyads). Between and within siblings influence processes were examined as a function of relative levels of parental coercion and hostility to test the hypothesis that aggression contagion between twins occurs only among dyads who experience parental coerciveness. Teacher reports of reactive and proactive aggression were collected for each twin in kindergarten (M = 6.04 years; SD = 0.27) and in first grade (M = 7.08 years; SD = 0.27). Families were divided into relatively low, average, and relatively high parental coercion-hostility groups on the basis of maternal reports collected when the children were 5 years old. In families with relatively high levels of parental coercion-hostility, there was evidence of between-sibling influence, such that one twin’s reactive aggression at age 6 predicted increases in the other twin’s reactive aggression from ages 6 to 7, and one twin’s proactive aggression at age 6 predicted increases in the other twin’s proactive aggression from ages 6 to 7. There was also evidence of within-sibling influence such that a child’s level of reactive aggression at age 6 predicted increases in the same child’s proactive aggression at age 7, regardless of parental coercion-hostility. The findings provide new information about the etiology of reactive and proactive aggression and individual differences in their developmental interplay. PMID:25683448

  6. Asthma status is associated with decreased risk of aggressive urothelial bladder cancer.

    Science.gov (United States)

    Rava, Marta; Czachorowski, Maciej J; Silverman, Debra; Márquez, Mirari; Kishore, Sirish; Tardón, Adonina; Serra, Consol; García-Closas, Montse; Garcia-Closas, Reina; Carrato, Alfredo; Rothman, Nathaniel; Real, Francisco X; Kogevinas, Manolis; Malats, Núria

    2018-02-01

    Previous studies suggested an association between atopic conditions and specific cancers. The results on the association with urothelial bladder cancer (UBC) are scarce and inconsistent. To evaluate the association between asthma and risk of UBC, we considered 936 cases and 1,022 controls from the Spanish Bladder Cancer/EPICURO Study (86% males, mean age 65.4 years), a multicenter and hospital-based case-control study conducted during 1998-2001. Participants were asked whether they had asthma and detailed information about occupational exposures, smoking habits, dietary factors, medical conditions and history of medication was collected through face-to-face questionnaires performed by trained interviewers. Since asthma and UBC might share risk factors, association between patients' characteristics and asthma was studied in UBC controls. Association between UBC and asthma was assessed using logistic regression unadjusted and adjusted for potential confounders. The complex interrelationships, direct and mediating effect of asthma on UBC, were appraised using counterfactual mediation models. Asthma was associated with a reduced risk of UBC (odds ratio (OR) = 0.54, 95% confidence interval (CI) 0.37, 0.79) after adjusting for a wide range of confounders. No mediating effect was identified. The reduced risk associated with asthma was restricted to patients with high-risk non-muscle invasive (OR = 0.25, 95%CI 0.10, 0.62) and muscle invasive UBC (OR = 0.32, 95%CI 0.15, 0.69). Our results support that asthma is associated with a decreased risk of UBC, especially among aggressive tumors. Further work on the relationship between asthma and other atopic conditions and cancer risk should shed light on the relationship between immune response mechanisms and bladder carcinogenesis. © 2017 UICC.

  7. End-of-life chemotherapy is associated with poor survival and aggressive care in patients with small cell lung cancer.

    Science.gov (United States)

    Zhu, Yingming; Tang, Ke; Zhao, Fen; Zang, Yuanwei; Wang, Xiaodong; Li, Zhenxiang; Sun, Xindong; Yu, Jinming

    2018-05-29

    Concerns regarding end-of-life (EOL) chemotherapy are being increasingly raised. Tumor chemosensitivity may influence the decision for aggressive chemotherapy near the EOL. Data on EOL chemotherapy in highly chemosensitive tumors, such as small cell lung cancer (SCLC), are scarce. A total of 143 SCLC decedents were consecutively included. Data about clinical factors and treatment modalities were obtained from the electronic medical records. The relationships among EOL chemotherapy, clinical features, overall survival (OS), and aggressive care were investigated. About 64% of patients had chemosensitive disease. In total, 30.8 and 16.1% of patients received EOL chemotherapy within the last 1 and 2 months of life, respectively. Younger age was associated with a higher rate of EOL chemotherapy. We determined that EOL chemotherapy was related to inferior OS not only in the entire group, but also in the chemosensitive subgroup. Furthermore, more intensive care was observed among patients who underwent EOL chemotherapy compared with those who did not. EOL chemotherapy was correlated with shorter survival and more aggressive care in patients with SCLC. More research is needed to develop indications for terminating palliative chemotherapy, to help physicians and patients with their difficult choices.

  8. Contributing Factors to Aggressive Behaviors in High School Students in Turkey

    Science.gov (United States)

    Kaya, Fadime; Bilgin, Hulya; Singer, Mark I.

    2012-01-01

    Violence among young people is an important public health topic as a universal problem. One of the recent issues concerning both the media and parents is the aggressive behavior among the high school students in Istanbul and the worldwide. The aim of this study was to investigate the types and rates of aggressive behavior and the contributing…

  9. A definition for aggressive disease in patients with HER-2 negative metastatic breast cancer: an expert consensus of the Spanish Society of Medical Oncology (SEOM).

    Science.gov (United States)

    González, A; Lluch, A; Aba, E; Albanell, J; Antón, A; Álvarez, I; Ayala, F; Barnadas, A; Calvo, L; Ciruelos, E; Cortés, J; de la Haba, J; López-Vega, J M; Martínez, E; Muñoz, M; Peláez, I; Redondo, A; Rodríguez, Á; Rodríguez, C A; Ruíz, A; Llombart, A

    2017-05-01

    To converge on an expert opinion to define aggressive disease in patients with HER2-negative mBC using a modified Delphi methodology. A panel of 21 breast cancer experts from the Spanish Society of Medical Oncology agreed upon a survey which comprised 47 questions that were grouped into three sections: relevance for defining aggressive disease, aggressive disease criteria and therapeutic goals. Answers were rated using a 9-point Likert scale of relevance or agreement. Among the 88 oncologists that were invited to participate, 81 answered the first round (92%), 70 answered the second round (80%), and 67 answered the third round (76%) of the survey. There was strong agreement regarding the fact that identifying patients with aggressive disease needs to be adequately addressed to help practitioners to decide the best treatment options for patients with HER2-negative mBC. The factors that were considered to be strongly relevant to classifying patients with aggressive HER2-negative mBC were a high tumor burden, a disease-free interval of less than 12-24 months after surgery, the presence of progressive disease during adjuvant or neoadjuvant chemotherapy and having a triple-negative phenotype. The main therapeutic goals were controlling symptoms, improving quality of life and increasing the time to progression and overall survival. High tumor burden, time to recurrence after prior therapy and having a triple-negative phenotype were the prognostic factors for which the greatest consensus was found for identifying patients with aggressive HER2-negative mBC. Identifying patients with aggressive disease leads to different therapeutic approaches.

  10. Disseminated breast cancer cells acquire a highly malignant and aggressive metastatic phenotype during metastatic latency in the bone.

    Directory of Open Access Journals (Sweden)

    Carolyn G Marsden

    Full Text Available BACKGROUND: Disseminated tumor cells (DTCs in the bone marrow may exist in a dormant state for extended periods of time, maintaining the ability to proliferate upon activation, engraft at new sites, and form detectable metastases. However, understanding of the behavior and biology of dormant breast cancer cells in the bone marrow niche remains limited, as well as their potential involvement in tumor recurrence and metastasis. Therefore, the purpose of this study was to investigate the tumorigenicity and metastatic potential of dormant disseminated breast cancer cells (prior to activation in the bone marrow. METHODOLOGY/PRINCIPAL FINDINGS: Total bone marrow, isolated from mice previously injected with tumorspheres into the mammary fat pad, was injected into the mammary fat pad of NUDE mice. As a negative control, bone marrow isolated from non-injected mice was injected into the mammary fat pad of NUDE mice. The resultant tumors were analyzed by immunohistochemistry for expression of epithelial and mesenchymal markers. Mouse lungs, livers, and kidneys were analyzed by H+E staining to detect metastases. The injection of bone marrow isolated from mice previously injected with tumorspheres into the mammary fat pad, resulted in large tumor formation in the mammary fat pad 2 months post-injection. However, the injection of bone marrow isolated from non-injected mice did not result in tumor formation in the mammary fat pad. The DTC-derived tumors exhibited accelerated development of metastatic lesions within the lung, liver and kidney. The resultant tumors and the majority of metastatic lesions within the lung and liver exhibited a mesenchymal-like phenotype. CONCLUSIONS/SIGNIFICANCE: Dormant DTCs within the bone marrow are highly malignant upon injection into the mammary fat pad, with the accelerated development of metastatic lesions within the lung, liver and kidney. These results suggest the acquisition of a more aggressive phenotype of DTCs during

  11. Agreeableness and alcohol-related aggression: the mediating effect of trait aggressivity.

    Science.gov (United States)

    Miller, Cameron A; Parrott, Dominic J; Giancola, Peter R

    2009-12-01

    This study investigated the mediating effect of trait aggressivity on the relation between agreeableness and alcohol-related aggression in a laboratory setting. Participants were 116 healthy male social drinkers between 21 and 30 years of age. Agreeableness and trait aggressivity were measured using the Big Five Inventory and the Buss-Perry Aggression Questionnaire, respectively. Following the consumption of an alcohol or no-alcohol control beverage, participants completed a modified version of the Taylor Aggression Paradigm, in which electric shocks were received from and administered to a fictitious opponent during a competitive task. Aggression was operationalized as the proportion of the most extreme shocks delivered to the fictitious opponent under conditions of low and high provocation. Results indicated that lower levels of agreeableness were associated with higher levels of trait aggressivity. In turn, higher levels of trait aggressivity predicted extreme aggression in intoxicated, but not sober, participants under low, but not high, provocation. Findings highlight the importance of examining determinants of intoxicated aggression within a broader theoretical framework of personality.

  12. Aldehyde dehydrogenase (ALDH activity does not select for cells with enhanced aggressive properties in malignant melanoma.

    Directory of Open Access Journals (Sweden)

    Lina Prasmickaite

    Full Text Available BACKGROUND: Malignant melanoma is an exceptionally aggressive, drug-resistant and heterogeneous cancer. Recently it has been shown that melanoma cells with high clonogenic and tumourigenic abilities are common, but markers distinguishing such cells from cells lacking these abilities have not been identified. There is therefore no definite evidence that an exclusive cell subpopulation, i.e. cancer stem cells (CSC, exists in malignant melanoma. Rather, it is suggested that multiple cell populations are implicated in initiation and progression of the disease, making it of importance to identify subpopulations with elevated aggressive properties. METHODS AND FINDINGS: In several other cancer forms, Aldehyde Dehydrogenase (ALDH, which plays a role in stem cell biology and resistance, is a valuable functional marker for identification of cells that show enhanced aggressiveness and drug-resistance. Furthermore, the presence of ALDH(+ cells is linked to poor clinical prognosis in these cancers. By analyzing cell cultures, xenografts and patient biopsies, we showed that aggressive melanoma harboured a large, distinguishable ALDH(+ subpopulation. In vivo, ALDH(+ cells gave rise to ALDH(- cells, while the opposite conversion was rare, indicating a higher abilities of ALDH(+ cells to reestablish tumour heterogeneity with respect to the ALDH phenotype. However, both ALDH(+ and ALDH(- cells demonstrated similarly high abilities for clone formation in vitro and tumour initiation in vivo. Furthermore, both subpopulations showed similar sensitivity to the anti-melanoma drugs, dacarbazine and lexatumumab. CONCLUSIONS: These findings suggest that ALDH does not distinguish tumour-initiating and/or therapy-resistant cells, implying that the ALDH phenotype is not associated with more-aggressive subpopulations in malignant melanoma, and arguing against ALDH as a "universal" marker. Besides, it was shown that the ability to reestablish tumour heterogeneity is not

  13. Aggression-related alcohol expectancies and barroom aggression among construction tradespeople.

    Science.gov (United States)

    Zinkiewicz, Lucy; Smith, Georgia; Burn, Michele; Litherland, Steven; Wells, Samantha; Graham, Kathryn; Miller, Peter

    2016-09-01

    Few studies have investigated the relationship of barroom aggression with both general and barroom-specific alcohol expectancies. The present study investigated these associations in a rarely studied and high-risk population: construction tradespeople. Male construction tradespeople (n = 211) aged 18-35 years (M = 21.91, SD = 4.08 years) participated in a face-to-face questionnaire assessing general and barroom-specific alcohol expectancies and perpetration of physical and verbal barroom aggression as well as control variables, age, alcohol consumption and trait aggression. Sequential logistic regression analyses revealed that general alcohol-aggression expectancies of courage or dominance were not predictive of either verbal or physical barroom aggression after controlling for age, alcohol consumption and trait aggression. However, barroom-specific alcohol expectancies were associated with both verbal and physical barroom aggression, with positive associations found for expected hyper-emotionality and protective effects for expected cognitive impairment. In a population where rates of risky drinking and barroom aggression are high, specific expectations about the effects of drinking in bars may influence subsequent aggressive behaviour in bars. [Zinkiewicz L, Smith G, Burn M, Litherland S, Wells S, Graham K, Miller P. Aggression-related alcohol expectancies and barroom aggression among construction tradespeople. Drug Alcohol Rev 2016;35:549-556]. © 2015 Australasian Professional Society on Alcohol and other Drugs.

  14. Contrast-enhanced transrectal ultrasound for prediction of prostate cancer aggressiveness: The role of normal peripheral zone time-intensity curves.

    Science.gov (United States)

    Huang, Hui; Zhu, Zheng-Qiu; Zhou, Zheng-Guo; Chen, Ling-Shan; Zhao, Ming; Zhang, Yang; Li, Hong-Bo; Yin, Li-Ping

    2016-12-08

    To assess the role of time-intensity curves (TICs) of the normal peripheral zone (PZ) in the identification of biopsy-proven prostate nodules using contrast-enhanced transrectal ultrasound (CETRUS). This study included 132 patients with 134 prostate PZ nodules. Arrival time (AT), peak intensity (PI), mean transit time (MTT), area under the curve (AUC), time from peak to one half (TPH), wash in slope (WIS) and time to peak (TTP) were analyzed using multivariate linear logistic regression and receiver operating characteristic (ROC) curves to assess whether combining nodule TICs with normal PZ TICs improved the prediction of prostate cancer (PCa) aggressiveness. The PI, AUC (p < 0.001 for both), MTT and TPH (p = 0.011 and 0.040 respectively) values of the malignant nodules were significantly higher than those of the benign nodules. Incorporating the PI and AUC values (both, p < 0.001) of the normal PZ TIC, but not the MTT and TPH values (p = 0.076 and 0.159 respectively), significantly improved the AUC for prediction of malignancy (PI: 0.784-0.923; AUC: 0.758-0.891) and assessment of cancer aggressiveness (p < 0.001). Thus, all these findings indicate that incorporating normal PZ TICs with nodule TICs in CETRUS readings can improve the diagnostic accuracy for PCa and cancer aggressiveness assessment.

  15. Diagnostic accuracy of prostate health index to identify aggressive prostate cancer. An Institutional validation study.

    Science.gov (United States)

    Morote, J; Celma, A; Planas, J; Placer, J; Ferrer, R; de Torres, I; Pacciuci, R; Olivan, M

    2016-01-01

    New generations of tumor markers used to detect prostate cancer (PCa) should be able to discriminate men with aggressive PCa of those without PCa or nonaggressive tumors. The objective of this study has been to validate Prostate Health Index (PHI) as a marker of aggressive PCa in one academic institution. PHI was assessed in 357 men scheduled to prostatic biopsy between June of 2013 and July 2014 in one academic institution. Thereafter a subset of 183 men younger than 75 years and total PSA (tPSA) between 3.0 and 10.0 ng/mL, scheduled to it first prostatic biopsy, was retrospectively selected for this study. Twelve cores TRUS guided biopsy, under local anaesthesia, was performed in all cases. Total PSA, free PSA (fPSA), and [-2] proPSA (p2PSA) and prostate volume were determined before the procedure and %fPSA, PSA density (PSAd) and PHI were calculated. Aggressive tumors were considered if any Gleason 4 pattern was found. PHI was compared to %fPSA and PSAd through their ROC curves. Thresholds to detect 90%, 95% of all tumors and 95% and 100% of aggressive tumors were estimated and rates of unnecessary avoided biopsies were calculated and compared. The rate of PCa detection was 37.2% (68) and the rate of aggressive tumors was 24.6% (45). The PHI area under the curve was higher than those of %fPSA and PSAd to detect any PCa (0.749 vs 0.606 and 0.668 respectively) or to detect only aggressive tumors (0.786 vs 0.677 and 0.708 respectively), however, significant differences were not found. The avoided biopsy rates to detect 95% of aggressive tumors were 20.2% for PHI, 14.8% for %fPSA, and 23.5% for PSAd. Even more, to detect all aggressive tumors these rates dropped to 4.9% for PHI, 9.3% for %fPSA, and 7.9% for PSAd. PHI seems a good marker to PCa diagnosis. However, PHI was not superior to %fPSA and PSAd to identify at least 95% of aggressive tumors. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer

    Science.gov (United States)

    2016-12-01

    prostatectomy samples, intraprostatic lipid as measured by MRSI and prostate tumor aggressiveness. 3) To quantify key metabolic intermediates involved in...lipid as measured by 1H MRSI, and prostate tumor aggressiveness; and 3) quantify the association between key metabolic intermediates involved in lipid

  17. Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, suppresses vasculogenic mimicry and proliferation of highly aggressive pancreatic cancer PaTu8988 cells

    International Nuclear Information System (INIS)

    Xu, Xing-dong; Yang, Lan; Zheng, Li-yun; Pan, Yan-yan; Cao, Zhi-fei; Zhang, Zhi-qing; Zhou, Quan-sheng; Yang, Bo; Cao, Cong

    2014-01-01

    Pancreatic cancer is one of the most aggressive human malignancies with a extremely low 5-year survival rate. Hence, the search for more effective anti-pancreatic cancer agents is urgent. PaTu8988 pancreatic cancer cells were treated with different concentrations of suberoylanilide hydroxamic acid (SAHA), cell survival, proliferation, migration and vasculogenic mimicry (VM) were analyzed. Associated signaling changes were also analyzed by RT-PCR and Western blots. Here, we reported that SAHA, a histone deacetylase inhibitor (HDACi), exerted significant inhibitory efficiency against pancreatic cancer cell survival, proliferation, migration and VM. SAHA dose-dependently inhibited PaTu8988 pancreatic cancer cell growth with the IC-50 of 3.4 ± 0. 7 μM. Meanwhile, SAHA suppressed PaTu8988 cell cycle progression through inducing G2/M arrest, which was associated with cyclin-dependent kinase 1 (CDK-1)/cyclin-B1 degradation and p21/p27 upregulation. Further, SAHA induced both apoptotic and non-apoptotic death of PaTu8988 cells. Significantly, SAHA suppressed PaTu8988 cell in vitro migration and cell-dominant tube formation or VM, which was accompanied by semaphorin-4D (Sema-4D) and integrin-β5 down-regulation. Our evidences showed that Akt activation might be important for Sema-4D expression in PaTu8988 cells, and SAHA-induced Sema-4D down-regulation might be associated with Akt inhibition. This study is among the first to report the VM formation in cultured human pancreatic cancer cells. And we provided strong evidence to suggest that SAHA executes significant anti-VM efficiency in the progressive pancreatic cancer cells. Thus, SAHA could be further investigated as a promising anti-pancreatic cancer agent

  18. Long-Term Remission of an Aggressive Sebaceous Carcinoma following Chemotherapy

    Science.gov (United States)

    Orcurto, Angela; Gay, Béatrice E.; Sozzi, Wendy Jeanneret; Gilliet, Michel; Leyvraz, Serge

    2014-01-01

    Sebaceous carcinoma (SC) is an uncommon neoplasm manifesting itself either in the eyelid or extraocularly in the head and neck area. Surgery is the standard of care. Irradiation is rarely proposed as monotherapy but is frequently administered as an adjuvant regimen following surgical resection. There is no known strategy concerning chemotherapeutic treatment in highly aggressive recurrent – or metastatic – forms of the disease. Our patient presented with an aggressive SC of the scalp recurring after multiple excisions and local radiotherapy. Chemotherapy with 5-fluorouracil, cisplatin and docetaxel was then initiated; 4 cycles were administered, followed by capecitabine maintenance. Shortly after starting chemotherapy, dermal lesions had completely disappeared and radiological response could be seen. The patient experienced an extended period (>20 months) of complete remission. In this report, we show an excellent response of a highly aggressive SC after a combination of chemotherapy as for head and neck cancers. PMID:24748864

  19. Chemokine (C-X-C) ligand 1 (CXCL1) protein expression is increased in aggressive bladder cancers

    International Nuclear Information System (INIS)

    Miyake, Makito; Lawton, Adrienne; Goodison, Steve; Urquidi, Virginia; Gomes-Giacoia, Evan; Zhang, Ge; Ross, Shanti; Kim, Jeongsoon; Rosser, Charles J

    2013-01-01

    Chemokines, including chemokine (C-X-C motif) ligand 1 (CXCL1), may regulate tumor epithelial-stromal interactions that facilitate tumor growth and invasion. Studies have linked CXCL1 expression to gastric, colon and skin cancers, but limited studies to date have described CXCL1 protein expression in human bladder cancer (BCa). CXCL1 protein expression was examined in 152 bladder tissue specimens (142 BCa) by immunohistochemical staining. The expression of CXCL1 was scored by assigning a combined score based on the proportion of cells staining and intensity of staining. CXCL1 expression patterns were correlated with clinicopathological features and follow-up data. CXCL1 protein expression was present in cancerous tissues, but was entirely absent in benign tissue. CXCL1 combined immunostaining score was significantly higher in high-grade tumors relative to low-grade tumors (p = 0.012). Similarly, CXCL1 combined immunostaining score was higher in high stage tumors (T2-T4) than in low stage tumors (Ta-T1) (p < 0.0001). An increase in the combined immunostaining score of CXCL1 was also associated with reduced disease-specific survival. To date, this is the largest study describing increased CXCL1 protein expression in more aggressive phenotypes in human BCa. Further studies are warranted to define the role CXCL1 plays in bladder carcinogenesis and progression

  20. The Immunohistochemical Analysis of SOCS3 Protein Identifies a Subgroup of Prostatic Cancer Biopsies With Aggressive Behavior.

    Science.gov (United States)

    Pierconti, Francesco; Martini, Maurizio; Cenci, Tonia; Larocca, Luigi M

    Recently, we demonstrated that hypermethylation of SOCS3 determines a significant reduction of its mRNA and protein expression and identifies a subgroup of prostate cancer with aggressive behavior. In this paper, our objective was to investigate whether the immunohistochemical expression of the SOCS3 protein could represent an alternative method to molecular analysis for the individualization of aggressive prostate carcinoma. We analyzed the SOCS3 immunohistochemical expression in 65 patients undergoing biopsies at the Institute of Urology of our hospital between September 2011 and October 2011 (median age, 66.4 y; range, 50 to 73 y), and in 35 cases, a subset of 65 cases originally used for the immunohistochemical study, we studied the methylation status of the SOCS3 promoter. We found that the percentage of cases with SOCS3 negativity (-) or with SOCS3 weak staining in <50% of the neoplastic glands (+/-) correlated to the worst prognosis in terms of the Gleason score (P=0.0001; Fisher's exact test), the pT stage (P=0.012; Fisher's exact test), and progression-free survival (P=0.0334; hazard ratio, 0.34; and 95% confidence interval, from 0.1261 to 0.9188). Moreover, some cases with an SOCS3 unmethylated pattern showed SOCS3-negative immunostaining (-) or SOCS3-negative glands with weak cytoplasmatic staining in <50% of the neoplastic glands (+/-). Our data suggest that in prostatic cancer biopsies, the immunohistochemical analysis of SOCS3 protein expression may provide a method that is less expensive and easier to apply than SOCS3 methylation analysis for the distinction of a subgroup of prostate cancer with a more aggressive behavior.

  1. A single social defeat reduces aggression in a highly aggressive strain of Drosophila

    OpenAIRE

    Penn, Jill K. M.; Zito, Michael F.; Kravitz, Edward A.

    2010-01-01

    Genes and prior experience both influence the behavior of animals, but the relative contribution of each to fighting behavior in Drosophila remains unclear. To address this issue, we bred hyperaggressive flies by selecting winners of fights over 34–37 generations. Males of this strain initiate fights sooner, retaliate more often, and regularly defeat opponents from the nonselected parent Canton-S strain. After a defeat, however, these highly aggressive flies lose their second fights against s...

  2. RKIP inhibition in cervical cancer is associated with higher tumor aggressive behavior and resistance to cisplatin therapy.

    Directory of Open Access Journals (Sweden)

    Olga Martinho

    Full Text Available Cervical cancer is one of the most common cancers in women worldwide, being high-risk group the HPV infected, the leading etiological factor. The raf kinase inhibitory protein (RKIP has been associated with tumor progression and metastasis in several human neoplasms, however its role on cervical cancer is unclear. In the present study, 259 uterine cervix tissues, including cervicitis, cervical intraepithelial lesions and carcinomas, were analyzed for RKIP expression by immunohistochemistry. We found that RKIP expression was significantly decreased during malignant progression, being highly expressed in non-neoplastic tissues (54% of the samples; 73/135, and expressed at low levels in the cervix invasive carcinomas (∼15% (19/124. Following in vitro downregulation of RKIP, we observed a viability and proliferative advantage of RKIP-inhibited cells over time, which was associated with an altered cell cycle distribution and higher colony number in a colony formation assay. An in vitro wound healing assay showed that RKIP abrogation is associated with increased migratory capability. RKIP downregulation was also associated with an increased vascularization of the tumors in vivo using a CAM assay. Furthermore, RKIP inhibition induced cervical cancer cells apoptotic resistance to cisplatin treatment. In conclusion, we described that RKIP protein is significantly depleted during the malignant progression of cervical tumors. Despite the lack of association with patient clinical outcome, we demonstrate, in vitro and in vivo, that loss of RKIP expression can be one of the factors that are behind the aggressiveness, malignant progression and chemotherapy resistance of cervical cancer.

  3. Peer group self-identification as a predictor of relational and physical aggression among high school students.

    Science.gov (United States)

    Pokhrel, Pallav; Sussman, Steven; Black, David; Sun, Ping

    2010-05-01

    Adolescent peer group self-identification refers to adolescents' affiliation with reputation-based peer groups such as "Goths" or "Jocks." These groups tend to vary on normative characteristics, including the group members' attitudes and behaviors. This article examined whether adolescents' baseline peer group self-identification predicted their self-reported relational and physical aggression 1 year later. Self-report data were collected from 1614 students from 9 regular and 9 continuation (alternative) high schools in Southern California, at baseline and 1-year follow-up. Subjects' mean baseline age was 15.21 years (SD = 1.18) and 51.6% of the subjects were female. Findings indicated that compared with self-identified "Regular" or "Normal" students, adolescents who identified with high-risk peer groups (eg, "Druggies,"Goths") tended to report higher relational and physical aggression 1 year later, controlling for baseline aggression and demographic variables. In addition, adolescents' self-identification with high-status peer groups (eg, "Jocks,"Populars") was predictive of higher relational aggression 1 year later. Gender and school type (ie, regular vs continuation) were not found to moderate these effects. It appears that peer group self-identification is a salient predictor of physical and relational aggression across gender and school type. Adolescents who identify with high-risk peer groups tend to report higher levels of physical as well as relational aggression in the future. In addition, adolescents who affiliate with elite groups tend to become more relationally aggressive over time. School-based prevention programs targeting aggression may benefit from addressing the impacts of peer group self-identification on adolescents' aggressive behavior.

  4. Paradoxical Association of Postoperative Plasma Sphingosine-1-Phosphate with Breast Cancer Aggressiveness and Chemotherapy

    Directory of Open Access Journals (Sweden)

    Rajesh Ramanathan

    2017-01-01

    Full Text Available Sphingosine-1-phosphate (S1P is a bioactive lipid mediator that has been shown to serve an important regulatory function in breast cancer progression. This study analyzes plasma S1P levels in breast cancer patients undergoing adjuvant therapy as compared to healthy control volunteers. 452 plasma S1P samples among 158 breast cancer patients, along with 20 healthy control volunteers, were analyzed. Mean S1P levels did not significantly differ between cancer patients and controls. Smoking was associated with higher S1P levels in cancer patients. Baseline S1P levels had weak inverse correlation with levels of the inflammatory mediator interleukin- (IL- 17 and CCL-2 and positive correlation with tumor necrosis factor alpha (TNF-α. Midpoint S1P levels during adjuvant therapy were lower than baseline, with near return to baseline after completion, indicating a relationship between chemotherapy and circulating S1P. While stage of disease did not correlate with plasma S1P levels, they were lower among patients with Her2-enriched and triple-negative breast cancer as compared to luminal-type breast cancer. Plasma S1P levels are paradoxically suppressed in aggressive breast cancer and during adjuvant chemotherapy, which raises the possibility that postoperative plasma S1P levels do not reflect S1P secretion from resected breast cancer.

  5. Causes of Death in Men With Prevalent Diabetes and Newly Diagnosed High- Versus Favorable-Risk Prostate Cancer

    International Nuclear Information System (INIS)

    D'Amico, Anthony V.; Braccioforte, Michelle H.; Moran, Brian J.; Chen, Ming-Hui

    2010-01-01

    Purpose: To determine whether prevalent diabetes mellitus (pDM) affects the presentation, extent of radiotherapy, or prostate cancer (PCa)-specific mortality (PCSM) and whether PCa aggressiveness affects the risk of non-PCSM, DM-related mortality, and all-cause mortality in men with pDM. Methods: Between October 1997 and July 2907, 5,279 men treated at the Chicago Prostate Cancer Center with radiotherapy for PCa were included in the study. Logistic and competing risk regression analyses were performed to assess whether pDM was associated with high-grade PCa, less aggressive radiotherapy, and an increased risk of PCSM. Competing risks and Cox regression analyses were performed to assess whether PCa aggressiveness described by risk group in men with pDM was associated with the risk of non-PCSM, DM-related mortality, and all-cause mortality. Analyses were adjusted for predictors of high-grade PCa and factors that could affect treatment extent and mortality. Results: Men with pDM were more likely (adjusted hazard ratio [AHR], 1.9; 95% confidence interval [CI], 1.3-2.7; p = .002) to present with high-grade PCa but were not treated less aggressively (p = .33) and did not have an increased risk of PCSM (p = .58) compared to men without pDM. Among the men with pDM, high-risk PCa was associated with a greater risk of non-PCSM (AHR, 2.2; 95% CI, 1.1-4.5; p = .035), DM-related mortality (AHR, 5.2; 95% CI, 2.0-14.0; p = .001), and all-cause mortality (AHR, 2.4; 95% CI, 1.2-4.7; p = .01) compared to favorable-risk PCa. Conclusion: Aggressive management of pDM is warranted in men with high-risk PCa.

  6. Management of Skin Cancer in the High-Risk Patient.

    Science.gov (United States)

    Behan, James W; Sutton, Adam; Wysong, Ashley

    2016-12-01

    Skin cancer is the most common of human cancers and outnumbers all other types of cancer combined in the USA by over threefold. The majority of non-melanoma skin cancers are easily treated with surgery or locally destructive techniques performed under local anesthesia in the cost-effective outpatient setting. However, there is a subset of "high-risk" cases that prove challenging in terms of morbidity, mortality, adjuvant treatment required, as well as overall cost to the health care system. In our opinion, the term "high risk" when applied to skin cancer can mean one of three things: a high-risk tumor with aggressive histologic and/or clinical features with an elevated risk for local recurrence or regional/distant metastasis, a high-risk patient with the ongoing development of multiple skin cancers, and a high-risk patient based on immunosuppression. We have recently proposed classifying NMSC as a chronic disease in a certain subset of patients. Although no consensus definition exists for a chronic disease in medicine, there are three components that are present in most definitions: duration of at least 1 year, need for ongoing medical care, and functional impairment and/or alteration of activities of daily living (ADLs) and quality of life (QOL). Immunosuppression can refer to exogenous (organ or stem cell transplant patients,) or endogenous (HIV, leukemia, lymphoma, genodermatoses with DNA mismatch repair problems or other immunosuppression) causes. These patients are at risk for high-risk tumors and/or the development of multiple tumors.

  7. Irradiated riboflavin diminishes the aggressiveness of melanoma in vitro and in vivo

    NARCIS (Netherlands)

    Machado, Daisy; Shishido, Silvia M.; Queiroz, Karla C. S.; Oliveira, Diogo N.; Faria, Ana L. C.; Catharino, Rodrigo R.; Spek, C. Arnold; Ferreira, Carmen V.

    2013-01-01

    Melanoma is one of the most aggressive skin cancers due to its high capacity to metastasize. Treatment of metastatic melanomas is challenging for clinicians, as most therapeutic agents have failed to demonstrate improved survival. Thus, new candidates with antimetastatic activity are much needed.

  8. Tumor aggressiveness and patient outcome in cancer of the pancreas assessed by dynamic 18F-FDG PET/CT.

    Science.gov (United States)

    Epelbaum, Ron; Frenkel, Alex; Haddad, Riad; Sikorski, Natalia; Strauss, Ludwig G; Israel, Ora; Dimitrakopoulou-Strauss, Antonia

    2013-01-01

    This study aimed to assess the role of a quantitative dynamic PET model in pancreatic cancer as a potential index of tumor aggressiveness and predictor of survival. Seventy-one patients with (18)F-FDG-avid adenocarcinoma of the pancreas before treatment were recruited, including 27 with localized tumors (11 underwent pancreatectomy, and 16 had localized nonresectable tumors) and 44 with metastatic disease. Dynamic (18)F-FDG PET images were acquired over a 60-min period, followed by a whole-body PET/CT study. Quantitative data measurements were based on a 2-compartment model, and the following variables were calculated: VB (fractional blood volume in target area), K(1) and k(2) (kinetic membrane transport parameters), k(3) and k(4) (intracellular (18)F-FDG phosphorylation and dephosphorylation parameters, respectively), and (18)F-FDG INF (global (18)F-FDG influx). The single significant variable for overall survival (OS) in patients with localized disease was (18)F-FDG INF. Patients with a high (18)F-FDG INF (>0.033 min(-1)) had a median OS of 6 and 5 mo for nonresectable and resected tumors, respectively, versus 15 and 19 mo for a low (18)F-FDG INF in nonresectable and resected tumors, respectively (P measured by dynamic PET in newly diagnosed pancreatic cancer correlated with the aggressiveness of disease. The (18)F-FDG INF was the single most significant variable for OS in patients with localized disease, whether resectable or not.

  9. Double dose: High family conflict enhances the effect of media violence exposure on adolescents’ aggression

    NARCIS (Netherlands)

    Fikkers, K.M.; Piotrowski, J.T.; Weeda, W.D.; Vossen, H.G.M.; Valkenburg, P.M.

    2013-01-01

    We investigated how exposure to media violence and family conflict affects adolescents’ subsequent aggressive behavior. We expected a double dose effect, meaning that high media violence exposure would lead to higher levels of aggression for adolescents in high conflict families compared to low

  10. Physical and relational aggression as predictors of drug use: gender differences among high school students.

    Science.gov (United States)

    Skara, Silvana; Pokhrel, Pallav; Weiner, Michelle D; Sun, Ping; Dent, Clyde W; Sussman, Steve

    2008-12-01

    The present study investigated the longitudinal relationships between physical and relational aggression and later drug use, as moderated by gender. Self-reported data were gathered from 2064 high school students at pretest and 1-year post-test to test the hypotheses that (1) males would engage in more physical aggression than females, whereas females would engage in more relational aggression than males; and (2) physical aggression would be a stronger drug use predictor for males and relational aggression a stronger predictor for females. Results indicated that males reported engaging in more physical aggression than females at baseline; however, females and males reported engaging in similar rates of relational aggression. After controlling for relational aggression, baseline drug use, and demographic variables, physical aggression at baseline was found to predict alcohol use 1-year later for males but not for females. After controlling for physical aggression, baseline drug use, and demographic variables, relational aggression was found to predict cigarette use and marijuana use for females but not for males. However, relational aggression was found to predict later alcohol and hard drug equally across gender. These findings suggest that both physical and relational aggression are predictive of subsequent drug use and have important implications for violence and drug use prevention intervention efforts.

  11. Social cognitions, distress, and leadership self-efficacy: associations with aggression for high-risk minority youth.

    Science.gov (United States)

    Leff, Stephen S; Baker, Courtney N; Waasdorp, Tracy E; Vaughn, Nicole A; Bevans, Katherine B; Thomas, Nicole A; Guerra, Terry; Hausman, Alice J; Monopoli, W John

    2014-08-01

    Urban ethnic minority youth are often exposed to high levels of aggression and violence. As such, many aggression intervention programs that have been designed with suburban nonethnic minority youth have been used or slightly adapted in order to try and meet the needs of high-risk urban youth. The current study contributes to the literature base by examining how well a range of social-cognitive, emotional distress and victimization, and prosocial factors are related to youth aggression in a sample of urban youth. This study utilized data gathered from 109 9- to 15-year-old youth (36.7% male; 84.4% African American) and their parents or caregivers. A series of hierarchical multiple regressions were fit predicting youth aggression from social-cognitive variables, victimization and distress, and prosocial variables, controlling for youth gender and age. Each set of variables explained a significant and unique amount of the variance in youth aggressive behavior. The full model including all predictors accounted for 41% of the variance in aggression. Models suggest that youth with stronger beliefs supportive of violence, youth who experience more overt victimization, and youth who experience greater distress in overtly aggressive situations are likely to be more aggressive. In contrast, youth with higher self-esteem and youth who endorse greater leadership efficacy are likely to be less aggressive. Contrary to hypotheses, hostile attributional bias and knowledge of social information processing, experience of relational victimization, distress in relationally aggressive situations, and community engagement were not associated with aggression. Our study is one of the first to address these important questions for low-income, predominately ethnic minority urban youth, and it has clear implications for adapting aggression prevention programs to be culturally sensitive for urban African American youth.

  12. Gender differences in trajectories of relational aggression perpetration and victimization from middle to high school.

    Science.gov (United States)

    Orpinas, Pamela; McNicholas, Caroline; Nahapetyan, Lusine

    2015-01-01

    Relational aggression refers to harming others through damaging or manipulating peer relationships. In a cohort of students surveyed annually from middle to high school, this study identified groups of adolescents who followed distinct trajectories of perpetration and of victimization of relational aggression, compared the proportion of boys and girls in each trajectory, and examined the overlap between perpetration and victimization trajectories. The sample consisted of 620 randomly selected sixth graders. Students completed yearly surveys from Grade 6-12. We used group-based trajectory modeling to identify the trajectories. Adolescents followed three developmental trajectories of perpetration and three similar trajectories of victimization: Low (lowest aggression), Moderate, and High Declining (high in middle school, with a steep decline in high school). All trajectories declined from Grade 6-12. The largest groups were the Low perpetration (55%) and Low victimization (48%). Relational aggression trajectories differed by gender: more boys reported perpetration, and more girls reported victimization. For perpetration, slightly more boys than girls were classified in the two trajectories of higher aggression. For victimization, significantly fewer girls than boys were classified in the Low trajectory, and significantly more girls than boys were classified in the Moderate trajectory. There was substantial overlap of the perpetration and victimization trajectories. These findings highlight the importance of implementing programs to reduce relational aggression for boys and for girls. © 2014 Wiley Periodicals, Inc.

  13. Longitudinal Examination of Aggression and Study Skills From Middle to High School: Implications for Dropout Prevention.

    Science.gov (United States)

    Orpinas, Pamela; Raczynski, Katherine; Hsieh, Hsien-Lin; Nahapetyan, Lusine; Horne, Arthur M

    2018-03-01

    High school completion provides health and economic benefits. The purpose of this study is to describe dropout rates based on longitudinal trajectories of aggression and study skills using teacher ratings. The sample consisted of 620 randomly selected sixth graders. Every year from Grade 6 to 12, a teacher completed a nationally normed behavioral rating scale. We used latent class mixture modeling to identify the trajectories. Participants followed 3 trajectories of aggression (Low, Medium Desisting, and High Desisting) and 5 trajectories of study skills (Low, Average-Low, Decreasing, Increasing, and High). Over three-quarters of the sample were in stable trajectories of study skills over time. Most students in the High Desisting Aggression group were in the Low Study Skills group, and all students in the High Study Skills group were in the Low Aggression group. The overall dropout rate was 17%, but varied dramatically across combined aggression and study skills groups, ranging from 2% to 50%. The results highlight the importance of early prevention that combines academic enhancement and behavioral management for reducing school dropout. © 2018, American School Health Association.

  14. The Impact of Educational Intervention on Aggression Level among High School Students in Ilam-Iran

    Directory of Open Access Journals (Sweden)

    Adel Bahari

    2017-01-01

    Full Text Available BackgroundManagement and control of adolescence aggression improves constructive relationships, quality of life, and academic achievement. This research aimed to study the impact of educational intervention on reduction of aggression among male high school students in Ilam city, Iran.Materials and MethodsThis quasi-experimental intervention study using the pretest-posttest method was conducted on 70 aggressive male high school students in Ilam who were selected using the convenience sampling method. First, students were asked to fill out the Buss-Perry Aggression Questionnaire (BPAQand 70 of them with the highest score of aggression were selected as the sample. They received educational intervention for eight 90-minute sessions  during one month. Then post-test data were collected and follow-up at three months after the intervention and statistically analyzed using SPSS-20.ResultsThe mean age of subjects was 15.81±1.24 years old. 83% belonged to the urban community and 12.5% belonged to the rural community. The results showed that the educational intervention was effective in reduction of aggression levels and its four subscales (P

  15. Up-regulation of mitochondrial antioxidation signals in ovarian cancer cells with aggressive biologic behavior.

    Science.gov (United States)

    Wang, Yue; Dong, Li; Cui, Heng; Shen, Dan-hua; Wang, Ying; Chang, Xiao-hong; Fu, Tian-yun; Ye, Xue; Yao, Yuan-yang

    2011-05-01

    Recently, a high frequency of mutations in mitochondrial DNA (mtDNA) has been detected in ovarian cancer. To explore the alterations of proteins in mitochondria in ovarian cancer, a pair of human ovarian carcinoma cell lines (SKOV3/SKOV3.ip1) with different metastatic potentials was examined. Cancer cells SKOV3.ip1 were derived from the ascitic tumor cells of nude mice bearing a tumor of ovarian cancer cells SKOV3. SKOV3.ip1 exhibited a higher degree of migration potential than its paired cell line SKOV3. The proteins in the mitochondria of these two cells were isolated and separated by 2-D gel electrophoresis. The differently expressed proteins were extracted and identified using matrix assisted laser desorption ionisation/time-of-flight/time-of-flight (MALDI-TOF/TOF), and finally a selected protein candidate was further investigated by immunohistochemistry (IHC) method in nude mice bearing tumor tissues of these two cells. A total of 35 spots with different expressions were identified between the two cells using 2D-polyacrylamide gel electrophoresis (PAGE) approach. Among them, 17 spots were detected only in either SKOV3 or SKOV3.ip1 cells. Eighteen spots expressed different levels, with as much as a three-fold difference between the two cells. Twenty spots were analyzed using MALDI-TOF/TOF, and 11 of them were identified successfully; four were known to be located in mitochondria, including superoxide dismutase 2 (SOD2), fumarate hydratase (FH), mitochondrial ribosomal protein L38 (MRPL38), and mRNA turnover 4 homolog (MRTO4). An increased staining of SOD2 was observed in SKOV3.ip1 over that of SKOV3 in IHC analysis. Our results indicate that the enhanced antioxidation and metabolic potentials of ovarian cancer cells might contribute to their aggressive and metastatic behaviors. The underlying mechanism warrants further study.

  16. A 17-gene assay to predict prostate cancer aggressiveness in the context of Gleason grade heterogeneity, tumor multifocality, and biopsy undersampling.

    Science.gov (United States)

    Klein, Eric A; Cooperberg, Matthew R; Magi-Galluzzi, Cristina; Simko, Jeffry P; Falzarano, Sara M; Maddala, Tara; Chan, June M; Li, Jianbo; Cowan, Janet E; Tsiatis, Athanasios C; Cherbavaz, Diana B; Pelham, Robert J; Tenggara-Hunter, Imelda; Baehner, Frederick L; Knezevic, Dejan; Febbo, Phillip G; Shak, Steven; Kattan, Michael W; Lee, Mark; Carroll, Peter R

    2014-09-01

    Prostate tumor heterogeneity and biopsy undersampling pose challenges to accurate, individualized risk assessment for men with localized disease. To identify and validate a biopsy-based gene expression signature that predicts clinical recurrence, prostate cancer (PCa) death, and adverse pathology. Gene expression was quantified by reverse transcription-polymerase chain reaction for three studies-a discovery prostatectomy study (n=441), a biopsy study (n=167), and a prospectively designed, independent clinical validation study (n=395)-testing retrospectively collected needle biopsies from contemporary (1997-2011) patients with low to intermediate clinical risk who were candidates for active surveillance (AS). The main outcome measures defining aggressive PCa were clinical recurrence, PCa death, and adverse pathology at prostatectomy. Cox proportional hazards regression models were used to evaluate the association between gene expression and time to event end points. Results from the prostatectomy and biopsy studies were used to develop and lock a multigene-expression-based signature, called the Genomic Prostate Score (GPS); in the validation study, logistic regression was used to test the association between the GPS and pathologic stage and grade at prostatectomy. Decision-curve analysis and risk profiles were used together with clinical and pathologic characteristics to evaluate clinical utility. Of the 732 candidate genes analyzed, 288 (39%) were found to predict clinical recurrence despite heterogeneity and multifocality, and 198 (27%) were predictive of aggressive disease after adjustment for prostate-specific antigen, Gleason score, and clinical stage. Further analysis identified 17 genes representing multiple biological pathways that were combined into the GPS algorithm. In the validation study, GPS predicted high-grade (odds ratio [OR] per 20 GPS units: 2.3; 95% confidence interval [CI], 1.5-3.7; p<0.001) and high-stage (OR per 20 GPS units: 1.9; 95% CI, 1

  17. Double Dose: High Family Conflict Enhances the Effect of Media Violence Exposure on Adolescents’ Aggression

    Directory of Open Access Journals (Sweden)

    Patti M. Valkenburg

    2013-07-01

    Full Text Available We investigated how exposure to media violence and family conflict affects adolescents’ subsequent aggressive behavior. We expected a double dose effect, meaning that high media violence exposure would lead to higher levels of aggression for adolescents in high conflict families compared to low conflict families. A total of 499 adolescents (aged 10 to 14, 48% girls participated in a two-wave longitudinal survey (4-month interval. Survey questions assessed their exposure to violence on television and in electronic games, family conflict, and aggressive behavior. Analyses revealed a significant interaction between media violence and family conflict. In families with higher conflict, higher media violence exposure was related to increased subsequent aggression. This study is the first to show a double dose effect of media violence and family conflict on adolescents’ aggression. These findings underscore the important role of the family in shaping the effects of adolescents’ media use on their social development.

  18. Aggression and self-esteem

    OpenAIRE

    Fleischmann, Otakar

    2008-01-01

    In the research we focus on problems of self-esteem and aggress. The aim was to discover and describe if by university students an important relation between self-esteem and aggress exists, if there are some differences in self-esteem and aggress between women and men and individuals with pedagogical and non-pedagogical professional polarization. The self-esteem was followed on different levels- general, low, medium and high level as well as aggress levels. Besides general aggress we followed...

  19. Trichomonas vaginalis infection and risk of prostate cancer: associations by disease aggressiveness and race/ethnicity in the PLCO Trial.

    Science.gov (United States)

    Marous, Miguelle; Huang, Wen-Yi; Rabkin, Charles S; Hayes, Richard B; Alderete, John F; Rosner, Bernard; Grubb, Robert L; Winter, Anke C; Sutcliffe, Siobhan

    2017-08-01

    Results from previous sero-epidemiologic studies of Trichomonas vaginalis infection and prostate cancer (PCa) support a positive association between this sexually transmitted infection and aggressive PCa. However, findings from previous studies are not entirely consistent, and only one has investigated the possible relation between T. vaginalis seropositivity and PCa in African-American men who are at highest risk of both infection and PCa. Therefore, we examined this possible relation in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, including separate analyses for aggressive PCa and African-American men. We included a sample of participants from a previous nested case-control study of PCa, as well as all additional Caucasian, aggressive, and African-American cases diagnosed since the previous study (total n = 438 Gleason 7 Caucasian cases, 487 more advanced Caucasian cases (≥Gleason 8 or stage III/IV), 201 African-American cases, and 1216 controls). We tested baseline sera for T. vaginalis antibodies. No associations were observed for risk of Gleason 7 (odds ratio (OR) = 0.87, 95% confidence interval (CI) 0.55-1.37) or more advanced (OR = 0.90, 95% CI 0.58-1.38) PCa in Caucasian men, or for risk of any PCa (OR = 1.06, 95% CI 0.67-1.68) in African-American men. Our findings do not support an association between T. vaginalis infection and PCa.

  20. High-Throughput Sequencing of Germline and Tumor From Men with Early-Onset Metastatic Prostate Cancer

    Science.gov (United States)

    2016-12-01

    to previously-reported unselected populations suggesting that this may be used as a prognostic marker for aggressive disease in the future. Finally...although an ETV1 fusion was detected). Importantly, paired prostate cancer specimens—particularly those representing primary and distant metastases—are...two-sided Fisher’s exact test p=0.25) (8). These findings support TP53 alterations as a marker of aggressive prostate cancer, in addition to their

  1. Impact of cachexia on outcomes in aggressive lymphomas.

    Science.gov (United States)

    Karmali, Reem; Alrifai, Taha; Fughhi, Ibtihaj A M; Ng, Ronald; Chukkapalli, Vineela; Shah, Palmi; Basu, Sanjib; Nathan, Sunita; Szymanski-Grant, Kelly; Gordon, Leo I; Venugopal, Parameswaran; Penedo, Frank J; Borgia, Jeffrey A

    2017-06-01

    Cancer cachexia is defined as a state of involuntary weight loss, attributed to altered body composition with muscle mass loss and/or loss of adiposity. Identifying the association between cancer cachexia and outcomes may pave the way for novel agents that target the cancer cachexia process. Clinical parameters for measurement of cancer cachexia are needed. We conducted a single-institution retrospective analysis that included 86 NHL patients with the aim of identifying an association between cancer cachexia and outcomes in aggressive lymphomas using the cachexia index (CXI) suggested by Jafri et al. (Clin Med Insights Oncol 9:87-93, 15). Impact of cachexia factors on progression-free survival (PFS) and overall survival (OS) were assessed using log-rank test and Cox proportional hazards regression. Patients were dichotomized around the median CXI into "non-cachectic" (CXI ≥49.8, n = 41) and "cachectic" (CXI Cachexia as defined by the CXI is prognostic in aggressive lymphomas and implies that novel therapeutic strategies directed at reversing cachexia may improve survival in this population.

  2. Detection of non-aggressive stage IA lung cancer using chest computed tomography and positron emission tomography/computed tomography.

    Science.gov (United States)

    Shiono, Satoshi; Yanagawa, Naoki; Abiko, Masami; Sato, Toru

    2014-10-01

    In contrast to lung cancer with ground-glass opacity, the radiological investigation of solid lung cancer has not been well examined. The aim of this study was to explore chest computed tomography (CT) and positron emission tomography (PET)/CT findings with regard to outcomes after lung cancer surgery in order to radiologically classify clinical stage IA lung cancers by tumour aggressiveness. Three hundred and fifteen clinical stage IA patients were analysed. Four groups were defined by tumour solidity on CT and by the standardized uptake value (SUV) index on PET-CT (tumour maximum SUV/mean right liver lobe SUV). We analysed the association between radiological findings and both pathological invasiveness and postoperative outcome. Group A (n = 84) had an SUV index <1.0 and non-solid tumours, Group B (n = 24) had an SUV index <1.0 and solid tumours, Group C (n = 54) had an SUV index ≥1.0 and non-solid tumours, while Group D (n = 153) had an SUV index ≥1.0 and solid tumours. Invasive lung cancer was found in 2/84 (2.4%) patients in Group A, 1/24 (4.2%) in Group B, 13/54 (24.1%) in Group C and 58/153 (37.9%) in Group D (P < 0.01). The 5-year recurrence-free rate was 100% in Groups A and B, 90.3% in C and 65.7% in D (P < 0.01). The cancer-specific survival rate was 100% in A and B, 94.6% in C and 81.7% in D (P < 0.01). The present results suggest that preoperative PET/CT and thin-section CT findings provide important information for a selection of surgical procedures for clinical stage IA lung cancers. In clinical stage IA lung cancers displaying solid or non-solid density in thin-section findings, an SUV index <1.0 may be a better criterion for detecting non-aggressive lung cancer even in solid lung cancers. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  3. Lipocalin 2 expression is associated with aggressive features of endometrial cancer

    International Nuclear Information System (INIS)

    Mannelqvist, Monica; Akslen, Lars A; Stefansson, Ingunn M; Wik, Elisabeth; Kusonmano, Kanthida; Raeder, Maria B; Øyan, Anne M; Kalland, Karl-Henning; Moses, Marsha A; Salvesen, Helga B

    2012-01-01

    . Increased LCN2 expression is associated with aggressive features and poor prognosis in endometrial cancer

  4. Higher serum concentrations of vimentin and DAKP1 are associated with aggressive breast tumour phenotypes in Ghanaian women.

    Science.gov (United States)

    Arko-Boham, Benjamin; Lomotey, Justice Tanihu; Tetteh, Emmanuel Nomo; Tagoe, Emmanuel Ayitey; Aryee, Nii Ayite; Owusu, Ewurama Ampadu; Okai, Isaac; Blay, Richard Michael; Clegg-Lamptey, Joe-Nat

    2017-01-01

    Breast cancer, the most commonly diagnosed cancer among women and leading cause of cancer-related deaths worldwide, exhibits aggressive behavior in indigenous African women evidenced by high histologic grade tumours with low hormone receptor positivity. Aggressive breast cancers grow quickly, easily metastasize and recur and often have unfavourable outcomes. The current study investigated candidate genes that may regulate tumour aggression in Ghanaian women. We hypothesize that increased expression and function of certain genes other than the widely-held view attributing breast cancer aggression in African populations to their younger population age may be responsible for the aggressive nature of tumours. Employing ELISA, we assayed for vimentin and death-associated protein kinase 1 (DAPK1) from thawed archived (stored at -80 °C) serum samples obtained from 40 clinically confirmed Ghanaian breast cancer patients and 40 apparently healthy controls. Patients' clinical records and tumour parameters matching the samples were retrieved from the database of the hospital. ANOVA was used to compare means of serum protein concentration among groups while Chi-square analysis was used for the categorical data sets with p -value ≤0.05 considered significant. Multiple logistic regression analysis was conducted to determine the association between protein concentration and tumour parameters. Of the 80 samples, 27 (33.8%) and 53 (66.2%) were from young (<35 years) and old (≥35 years), respectively. Vimentin and DAPK1 concentration were higher in patients than controls with higher levels in "young" age group than "old" age group. Vimentin concentration was highest in grade 3 tumours followed by grade 2 and 1 but that for DAPK1 was not significant. For vimentin, tumour area strongly correlated with tumour grade ( r  = 0.696, p  < 0.05) but weakly correlated with tumour stage ( r  = 0.420, p  < 0.05). Patient's age correlated with DAPK1 concentration ( r  = 0

  5. Peer Relations and Peer Deviance as Predictors of Reactive and Proactive Aggression among High School Girls

    Science.gov (United States)

    Uz Bas, Asli; Öz Soysal, Fatma Selda

    2016-01-01

    This study aimed to investigate associations between reactive and proactive aggression and peer relations and peer deviance among high school girls. A total of 442 high school students participated in this study. Reactive-Proactive Aggression Questionnaire, the Peer Relations Scale, and the Peer Deviance Scale were used to collect data. Results…

  6. CXCR6, a newly defined biomarker of tissue-specific stem cell asymmetric self-renewal, identifies more aggressive human melanoma cancer stem cells.

    Directory of Open Access Journals (Sweden)

    Rouzbeh Taghizadeh

    2010-12-01

    Full Text Available A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growth and its origin from normal tissue cells. Recent investigations of a variety of tumor types have shown that phenotypically identifiable and isolable subfractions of cells possess the tumor-forming ability. In the present paper, using two lineage-related human melanoma cell lines, primary melanoma line IGR39 and its metastatic derivative line IGR37, two main observations are reported. The first one is the first phenotypic evidence to support the origin of melanoma cancer stem cells (CSCs from mutated tissue-specific stem cells; and the second one is the identification of a more aggressive subpopulation of CSCs in melanoma that are CXCR6+.We defined CXCR6 as a new biomarker for tissue-specific stem cell asymmetric self-renewal. Thus, the relationship between melanoma formation and ABCG2 and CXCR6 expression was investigated. Consistent with their non-metastatic character, unsorted IGR39 cells formed significantly smaller tumors than unsorted IGR37 cells. In addition, ABCG2+ cells produced tumors that had a 2-fold greater mass than tumors produced by unsorted cells or ABCG2- cells. CXCR6+ cells produced more aggressive tumors. CXCR6 identifies a more discrete subpopulation of cultured human melanoma cells with a more aggressive MCSC phenotype than cells selected on the basis of the ABCG2+ phenotype alone.The association of a more aggressive tumor phenotype with asymmetric self-renewal phenotype reveals a previously unrecognized aspect of tumor cell physiology. Namely, the retention of some tissue-specific stem cell attributes, like the ability to asymmetrically self-renew, impacts the natural history of human tumor development. Knowledge of this new aspect of tumor development and progression may provide new targets for cancer prevention and treatment.

  7. High loading of polygenic risk for ADHD in children with comorbid aggression

    DEFF Research Database (Denmark)

    Hamshere, Marian L; Langley, Kate; Martin, Joanna

    2013-01-01

    OBJECTIVE Although attention deficit hyperactivity disorder (ADHD) is highly heritable, genome-wide association studies (GWAS) have not yet identified any common genetic variants that contribute to risk. There is evidence that aggression or conduct disorder in children with ADHD indexes higher...... to those without comorbid conduct disorder. Association with symptom scores was tested using linear regression. RESULTS Polygenic risk for ADHD, derived from the meta-analysis, was higher in the independent ADHD group than in the comparison group. Polygenic score was significantly higher in ADHD case...... in individuals with comorbid aggression. The findings suggest that the previously published ADHD GWAS meta-analysis contains weak but true associations with common variants, support for which falls below genome-wide significance levels. The findings also highlight the fact that aggression in ADHD indexes genetic...

  8. Aggressive Treatment of Patients with Metastatic Colorectal Cancer Increases Survival: A Scandinavian Single-Center Experience

    Directory of Open Access Journals (Sweden)

    Kristoffer Watten Brudvik

    2013-01-01

    Full Text Available Background. We examined overall and disease-free survivals in a cohort of patients subjected to resection of liver metastasis from colorectal cancer (CRLM in a 10-year period when new treatment strategies were implemented. Methods. Data from 239 consecutive patients selected for liver resection of CRLM during the period from 2002 to 2011 at a single center were used to estimate overall and disease-free survival. The results were assessed against new treatment strategies and established risk factors. Results. The 5-year cumulative overall and disease-free survivals were 46 and 24%. The overall survival was the same after reresection, independently of the number of prior resections and irrespectively of the location of the recurrent disease. The time intervals between each recurrence were similar (11 ± 1 months. Patients with high tumor load given neoadjuvant chemotherapy had comparable survival to those with less extensive disease without neoadjuvant chemotherapy. Positive resection margin or resectable extrahepatic disease did not affect overall survival. Conclusion. Our data support that one still, and perhaps to an even greater extent, should seek an aggressive therapeutic strategy to achieve resectable status for recurrent hepatic and extrahepatic metastases. The data should be viewed in the context of recent advances in the understanding of cancer biology and the metastatic process.

  9. Trends in the aggressiveness of end-of-life care for Korean pediatric cancer patients who died in 2007-2010.

    Directory of Open Access Journals (Sweden)

    June Dong Park

    Full Text Available In light of the Korean Supreme Court's 2009 ruling favoring a patient's right to die with dignity, we evaluated trends in aggressive care in a cohort of pediatric cancer patients. Methods We conducted a population-based retrospective study that used administrative data for patients who died in 2007-2010 among the 5,203 pediatric cancer patients registered at the Korean Cancer Central Registry (KCCR during 2007-2009.In the time period covered, 696 patients died. The proportion who had received chemotherapy in the last 30 days of life decreased from 58.1% to 28.9% (P<0.001, those who received new chemotherapy in the same time period decreased from 55.2% to 15.1% (P<0.001, and those who received treatment in the last 2 weeks of life decreased from 51.4% to 21.7% (P<0.001. In the last 30 days of life, the proportion of patients whose hospital admission period was over 14 days increased from 70.5% to 82.5% (P = 0.03, the proportion who received cardiopulmonary resuscitation decreased from 28.6% to 9.6% (P<0.001, and we found no statistically significant trends in the proportion of emergency department visits, intensive care unit admissions, or mechanical ventilation.In this study, in contrast with earlier ones, the aggressiveness of end-of-life care of Korean pediatric cancer patients decreased dramatically.

  10. Reliability of multiparametric prostatic MRI quantitative data in the evaluation of prostate cancer aggressiveness

    Directory of Open Access Journals (Sweden)

    Haisam Atta

    2017-09-01

    Full Text Available Purpose: To compare the quantitative data of multiparametric prostatic MRI with Gleason scores of histopathological analysis. Materials and methods: One hundred twenty-two patients performed Multiparametric MRI of the prostate. Functional MRI quantitative data (including diffusion with mean ADC value and spectroscopic metabolic ratio where the DWI is employing b 50, 400, 800, 1000 and 2000 sec/mm2 and multivoxel MR spectroscopy compared with of Gleason scores of histopathological results. Malignant cases are classified into three groups according to their Gleason score as group I with Gleason score ≤6, group II Gleason score 7, while Gleason score 8–10 stratified as Group III. Results: The histopathological analysis reveals 78 malignant cases and 44 benign Cases. The significant statistical difference between group I and the other two groups (p < 0.001 regarding the quantitative mean ADC value and metabolic spectroscopic ratio. No significant statistical difference between group II and III with p = 0.2 for mean ADC difference and p = 0.8 for the metabolic spectroscopic ratio with a weak negative correlation between ADCand Gleason score [rs = −0.26] and significant positive correlation (p = 0.02 for MRSI metabolic ratio [rs = 0.2]. Conclusion: The quantitative data of functional imaging of the prostate is reliable in evaluating prostatic cancer aggressiveness and proper construction of therapeutic plan. Keywords: mpMRI prostate cancer aggressiveness

  11. [First-line treatment of lymphomas of "high grade malignancy" or "aggressive lymphomas"].

    Science.gov (United States)

    Reyes, F

    2001-11-01

    Main strategies used as first line treatment of aggressive lymphoma are the subject of this review. The evolution of histopathlogical classifications is reviewed and the concept of aggressive lymphoma is given. General principles of chemotherapy treatment and main prognostic factors that direct therapeutic decisions are described. The treatment modalities of localized and advanced disease are detailed, as well as the role of high-dose therapy with hematopoietic support. Finally, the major impact of immunotherapy based on the monoclonal anti-CD20 antibody is envisaged.

  12. High-mobility group box 1 released by autophagic cancer-associated fibroblasts maintains the stemness of luminal breast cancer cells.

    Science.gov (United States)

    Zhao, Xi-Long; Lin, Yong; Jiang, Jun; Tang, Zhuo; Yang, Shuai; Lu, Lu; Liang, Yan; Liu, Xue; Tan, Jiao; Hu, Xu-Gang; Niu, Qin; Fu, Wen-Juan; Yan, Ze-Xuan; Guo, De-Yu; Ping, Yi-Fang; Wang, Ji Ming; Zhang, Xia; Kung, Hsiang-Fu; Bian, Xiu-Wu; Yao, Xiao-Hong

    2017-11-01

    Cancer stem cells/cancer-initiating cells (CICs) and their microenvironmental niche play a vital role in malignant tumour recurrence and metastasis. Cancer-associated fibroblasts (CAFs) are major components of the niche of breast cancer-initiating cells (BCICs), and their interactions may profoundly affect breast cancer progression. Autophagy has been considered to be a critical process for CIC maintenance, but whether it is involved in the cross-talk between CAFs and CICs to affect tumourigenesis and pathological significance has not been determined. In this study, we found that the presence of CAFs containing high levels of microtubule-associated protein 1 light chain 3 (LC3II), a marker of autophagosomes, was associated with more aggressive luminal human breast cancer. CAFs in human luminal breast cancer tissues with high autophagy activity enriched BCICs with increased tumourigenicity. Mechanistically, autophagic CAFs released high-mobility group box 1 (HMGB1), which activated its receptor, Toll-like receptor (TLR) 4, expressed by luminal breast cancer cells, to enhance their stemness and tumourigenicity. Furthermore, immunohistochemistry of 180 luminal breast cancers revealed that high LC3II/TLR4 levels predicted an increased relapse rate and a poorer prognosis. Our findings demonstrate that autophagic CAFs play a critical role in promoting the progression of luminal breast cancer through an HMGB1-TLR4 axis, and that both autophagy in CAFs and TLR4 on breast cancer cells constitute potential therapeutic targets. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  13. Trans fat consumption and aggression.

    Directory of Open Access Journals (Sweden)

    Beatrice A Golomb

    Full Text Available Dietary trans fatty acids (dTFA are primarily synthetic compounds that have been introduced only recently; little is known about their behavioral effects. dTFA inhibit production of omega-3 fatty acids, which experimentally have been shown to reduce aggression. Potential behavioral effects of dTFA merit investigation. We sought to determine whether dTFA are associated with aggression/irritability. METHODOLGY/PRINICPAL FINDINGS: We capitalized on baseline dietary and behavioral assessments in an existing clinical trial to analyze the relationship of dTFA to aggression. Of 1,018 broadly sampled baseline subjects, the 945 adult men and women who brought a completed dietary survey to their baseline visit are the target of this analysis. Subjects (seen 1999-2004 were not on lipid medications, and were without LDL-cholesterol extremes, diabetes, HIV, cancer or heart disease. Outcomes assessed adverse behaviors with impact on others: Overt Aggression Scale Modified-aggression subscale (primary behavioral endpoint; Life History of Aggression; Conflict Tactics Scale; and self-rated impatience and irritability. The association of dTFA to aggression was analyzed via regression and ordinal logit, unadjusted and adjusted for potential confounders (sex, age, education, alcohol, and smoking. Additional analyses stratified on sex, age, and ethnicity, and examined the prospective association. Greater dTFA were strongly significantly associated with greater aggression, with dTFA more consistently predictive than other assessed aggression predictors. The relationship was upheld with adjustment for confounders, was preserved across sex, age, and ethnicity strata, and held cross-sectionally and prospectively.This study provides the first evidence linking dTFA with behavioral irritability and aggression. While confounding is always a concern in observational studies, factors including strength and consistency of association, biological gradient, temporality, and

  14. Aggression in children with behavioural/emotional difficulties: seeing aggression on television and video games

    OpenAIRE

    Mitrofan, O.; Paul, M.; Weich, S.; Spencer, N.

    2014-01-01

    Background: Mental health professionals are often asked to give advice about managing children’s aggression.\\ud Good quality evidence on contributory environmental factors such as seeing aggression on television and in video\\ud games is relatively lacking, although societal and professional concerns are high. This study investigated possible\\ud associations between seeing aggression in such media and the aggressive behaviour of children attending\\ud specialist outpatient child and adolescent ...

  15. Establishment of a novel human medulloblastoma cell line characterized by highly aggressive stem-like cells.

    Science.gov (United States)

    Silva, Patrícia Benites Gonçalves da; Rodini, Carolina Oliveira; Kaid, Carolini; Nakahata, Adriana Miti; Pereira, Márcia Cristina Leite; Matushita, Hamilton; Costa, Silvia Souza da; Okamoto, Oswaldo Keith

    2016-08-01

    Medulloblastoma is a highly aggressive brain tumor and one of the leading causes of morbidity and mortality related to childhood cancer. These tumors display differential ability to metastasize and respond to treatment, which reflects their high degree of heterogeneity at the genetic and molecular levels. Such heterogeneity of medulloblastoma brings an additional challenge to the understanding of its physiopathology and impacts the development of new therapeutic strategies. This translational effort has been the focus of most pre-clinical studies which invariably employ experimental models using human tumor cell lines. Nonetheless, compared to other cancers, relatively few cell lines of human medulloblastoma are available in central repositories, partly due to the rarity of these tumors and to the intrinsic difficulties in establishing continuous cell lines from pediatric brain tumors. Here, we report the establishment of a new human medulloblastoma cell line which, in comparison with the commonly used and well-established cell line Daoy, is characterized by enhanced proliferation and invasion capabilities, stem cell properties, increased chemoresistance, tumorigenicity in an orthotopic metastatic model, replication of original medulloblastoma behavior in vivo, strong chromosome structural instability and deregulation of genes involved in neural development. These features are advantageous for designing biologically relevant experimental models in clinically oriented studies, making this novel cell line, named USP-13-Med, instrumental for the study of medulloblastoma biology and treatment.

  16. 4-Acetylantroquinonol B suppresses autophagic flux and improves cisplatin sensitivity in highly aggressive epithelial cancer through the PI3K/Akt/mTOR/p70S6K signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Mingche [Graduate Institute of Biomedical Materials and Tissue Engineering, College of biomedical engineering, Taipei Medical University, Taipei, Taiwan (China); Department of Urology, Taipei Medical University Hospital, Taipei, Taiwan (China); Department of Urology, School of Medicine, college of Medicine, Taipei Medical University, Taipei, Taiwan (China); Bamodu, Oluwaseun Adebayo [Department of Hematology and Oncology, Cancer Center, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan (China); Department of Medical Research & Education, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan (China); Huang, Wen-Chien [Institute of Traditional Medicine, School of Medicine, National Yang Ming University, Taipei, Taiwan (China); Department of Surgery, Division of Thoracic Surgery, MacKay Memorial Hospital, Taipei, Taiwan (China); Zucha, Muhammad Ary [Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan (China); Lin, Yen-Kuang [Biostatistics and Research Consultation Center, Taipei Medical University, Taipei 11031, Taiwan (China); Wu, Alexander T.H. [The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan (China); Huang, Chun-Chih [Center for General Education, National Taitung University, Taitung, Taiwan (China); Lee, Wei-Hwa [Department of Pathology, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan (China); Yuan, Chiou-Chung [Obstetrics and Gynecology Department, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan (China); Hsiao, M. [Genomics Research Center, Academia Sinica, Taipei, Taiwan (China); Deng, Li [Beijing Bioprocess Key Laboratory, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing (China); Amoy-BUCT Industrial Bio-technovation Institute, Amoy (China); and others

    2017-06-15

    Targeting residual self-renewing, chemoresistant cancerous cells may represent the key to overcoming therapy resistance. The entry of these quiescent cells into an activated state is associated with high metabolic demand and autophagic flux. Therefore, modulating the autophagy pathway in aggressive carcinomas may be beneficial as a therapeutic modality. In this study, we evaluated the anti-tumor activities of 4-acetylantroquinonol B (4-AAQB) in chemoresistant ovarian cancer cells, particularly its ability to modulate autophagy through autophagy-related genes (Atg). Atg-5 was overexpressed in invasive ovarian cancer cell lines and tissue (OR: 5.133; P = 0.027) and depleting Atg-5 in ES-2 cell lines significantly induced apoptosis. 4-AAQB effectively suppressed viability of various subtypes of ovarian cancer. Cells with higher cisplatin-resistance were more responsive to 4-AAQB. For the first time, we demonstrate that 4-AAQB significantly suppress Atg-5 and Atg-7 expression with decreased autophagic flux in ovarian cancer cells via inhibition of the PI3K/Akt/mTOR/p70S6K signaling pathway. Similar to Atg-5 silencing, 4-AAQB-induced autophagy inhibition significantly enhanced cell death in vitro. These results are comparable to those of hydroxychloroquine (HCQ). In addition, 4-AAQB/cisplatin synergistically induced apoptosis in ovarian cancer cells. In vivo, 4-AAQB/cisplatin also significantly induced apoptosis and autophagy in an ES-2 mouse xenografts model. This is the first report demonstrating the efficacy of 4-AAQB alone or in combination with cisplatin on the suppression of ovarian cancer via Atg-5-dependent autophagy. We believe these findings will be beneficial in the development of a novel anti-ovarian cancer therapeutic strategy. - Highlights: • Atg-5 is overexpressed in ovarian cancer and silencing Atg-5 induces apoptosis. • 4-AAQB suppresses autophagy and PI3K/Akt/mTOR pathway. • 4-AAQB + cisplatin synergistically suppresses ovarian cancer via

  17. 4-Acetylantroquinonol B suppresses autophagic flux and improves cisplatin sensitivity in highly aggressive epithelial cancer through the PI3K/Akt/mTOR/p70S6K signaling pathway

    International Nuclear Information System (INIS)

    Liu, Mingche; Bamodu, Oluwaseun Adebayo; Huang, Wen-Chien; Zucha, Muhammad Ary; Lin, Yen-Kuang; Wu, Alexander T.H.; Huang, Chun-Chih; Lee, Wei-Hwa; Yuan, Chiou-Chung; Hsiao, M.; Deng, Li

    2017-01-01

    Targeting residual self-renewing, chemoresistant cancerous cells may represent the key to overcoming therapy resistance. The entry of these quiescent cells into an activated state is associated with high metabolic demand and autophagic flux. Therefore, modulating the autophagy pathway in aggressive carcinomas may be beneficial as a therapeutic modality. In this study, we evaluated the anti-tumor activities of 4-acetylantroquinonol B (4-AAQB) in chemoresistant ovarian cancer cells, particularly its ability to modulate autophagy through autophagy-related genes (Atg). Atg-5 was overexpressed in invasive ovarian cancer cell lines and tissue (OR: 5.133; P = 0.027) and depleting Atg-5 in ES-2 cell lines significantly induced apoptosis. 4-AAQB effectively suppressed viability of various subtypes of ovarian cancer. Cells with higher cisplatin-resistance were more responsive to 4-AAQB. For the first time, we demonstrate that 4-AAQB significantly suppress Atg-5 and Atg-7 expression with decreased autophagic flux in ovarian cancer cells via inhibition of the PI3K/Akt/mTOR/p70S6K signaling pathway. Similar to Atg-5 silencing, 4-AAQB-induced autophagy inhibition significantly enhanced cell death in vitro. These results are comparable to those of hydroxychloroquine (HCQ). In addition, 4-AAQB/cisplatin synergistically induced apoptosis in ovarian cancer cells. In vivo, 4-AAQB/cisplatin also significantly induced apoptosis and autophagy in an ES-2 mouse xenografts model. This is the first report demonstrating the efficacy of 4-AAQB alone or in combination with cisplatin on the suppression of ovarian cancer via Atg-5-dependent autophagy. We believe these findings will be beneficial in the development of a novel anti-ovarian cancer therapeutic strategy. - Highlights: • Atg-5 is overexpressed in ovarian cancer and silencing Atg-5 induces apoptosis. • 4-AAQB suppresses autophagy and PI3K/Akt/mTOR pathway. • 4-AAQB + cisplatin synergistically suppresses ovarian cancer via

  18. [Relationship among inattentive and hyperactive-impulsive behavior, aggression, and depression in Japanese elementary and junior high school students].

    Science.gov (United States)

    Noda, Wataru; Okada, Ryo; Tani, Iori; Ohnishi, Masafumi; Naoto, Mochizuki; Nakajima, Syunji; Tsujii, Masatsugu

    2013-06-01

    The present study examines the relationship among inattentive, and hyperactive-impulsive behavior, aggression, and depression in elementary school and junior high school students. The participants were 3,885 children and their teachers and caregivers. Children's inattentive and hyperactive-impulsive behavior was rated by their teachers and caregivers (ADHD-RS). Children rated aggression (HAQ-C) and depression (DSRS-C) themselves. Inattentive and hyperactive-impulsive behavior rated by teachers and caregivers were positively related to aggression and depression. Inattention predicted higher levels of aggression and depression. Inattentive and hyperactive-impulsive behavior as rated by teachers was more highly related to depression than those behaviors as rated by caregivers. The relationships among inattentive, and hyperactive-impulsive behavior, aggression, and depression were almost the same for both elementary school and junior high school students. This study suggests the importance of assessing inattentive and hyperactive-impulsive behavior from multiple views to examine the relationship between inattentive and hyperactive-impulsive behavior and mental health problems.

  19. Compulsive Addiction-like Aggressive Behavior in Mice.

    Science.gov (United States)

    Golden, Sam A; Heins, Conor; Venniro, Marco; Caprioli, Daniele; Zhang, Michelle; Epstein, David H; Shaham, Yavin

    2017-08-15

    Some people are highly motivated to seek aggressive encounters, and among those who have been incarcerated for such behavior, recidivism rates are high. These observations echo two core features of drug addiction: high motivation to seek addictive substances, despite adverse consequences, and high relapse rates. Here we used established rodent models of drug addiction to determine whether they would be sensitive to "addiction-like" features of aggression in CD-1 mice. In experiments 1 and 2, we trained older CD-1 mice to lever press for opportunities to attack younger C57BL6/J mice. We then tested them for relapse to aggression seeking after forced abstinence or punishment-induced suppression of aggression self-administration. In experiment 3, we trained a large cohort of CD-1 mice and tested them for choice-based voluntary suppression of aggression seeking, relapse to aggression seeking, progressive ratio responding, and punishment-induced suppression of aggression self-administration. We then used cluster analysis to identify patterns of individual differences in compulsive "addiction-like" aggressive behavior. In experiments 1 and 2, we observed strong motivation to acquire operant self-administration of opportunities to aggress and relapse vulnerability during abstinence. In experiment 3, cluster analysis of the aggression-related measures identified a subset of "addicted" mice (∼19%) that exhibited intense operant-reinforced attack behavior, decreased likelihood to select an alternative reinforcer over aggression, heightened relapse vulnerability and progressive ratio responding, and resilience to punishment-induced suppression of aggressive behavior. Using procedures established to model drug addiction, we showed that a subpopulation of CD-1 mice demonstrate "addiction-like" aggressive behavior, suggesting an evolutionary origin for compulsive aggression. Published by Elsevier Inc.

  20. The Relationship between Religious Commitment, Religious Involvement and Empathy with Aggression Among High School Students

    Directory of Open Access Journals (Sweden)

    M. Farhanfar

    2015-06-01

    Full Text Available The present study has been done to determine the effect of religious commitment and religious involvement with aggression and as a mediator variable empathy was considered. This is a descriptive - correlational study and the population was all high school students of Isfahan. The sample consisted of 321 high school students that were selected by cluster random multi-stage sampling method. Data were collected using Aggression Questionnaire (Rhine, 2006, Worthington Religious Commitment (2003, Hill and Hood Religious Involvement (1999, David Empathy (1983 and Demographic ascertained Questionnaire. For Statistical Analysis, Correlation Pierson, regression analysis and structural equation method was applied. Achieved results showed that the direct effect of religious commitment on the empathy of 0/07 and the direct effect of religious involvement on empathy: /025, (P≥0/0/1, while the indirect effect of religious commitment on -/0 0231 aggression and indirect effects of religious devotion is an aggression- 54/21 representing the inverse relationship between commitment an inverse relationship between religious commitment and religious involvement by the aggression and Results of structural equation modeling show that the model has appropriate fitting based on fitting indicators (P≥0/0/1. Although, the effect of religious commitment on empathy was not confirmed.

  1. Radio-induced breast cancers exhibiting aggressive anatomo-pathological characteristics: retrospective study of the long-term follow-up committee of the French Society of Child Cancers; Cancers du sein radio-induits presentant des caracteristiques anatomopathologiques agressives: etude retrospective du comite de suivi a long terme de la Societe francaise des cancers de l'enfant

    Energy Technology Data Exchange (ETDEWEB)

    Demoor, C.; Mahe, M.A.; Supiot, S. [ICO Rene-Gauducheau, Nantes (France); Vathaire, F. de [Inserm UMRS 1018, institut de cancerologie Gustave-Roussy, Villejuif (France); Oberlin, O. [Institut de cancerologie Gustave-Roussy, Villejuif (France); Noel, G. [Centre Paul-Strauss, Strasbourg (France); Brillaud, V. [Institut Bergonie, Bordeaux (France); Bernier, V. [Centre Alexis-Vautrin, Nancy (France); Laprie, A. [Institut Claudius-Regaud, Toulouse (France); Claude, L. [Centre Leon-Berard, Lyon (France)

    2011-10-15

    The authors report an analysis of clinical-pathological characteristics of radio-induced breast cancers registered in six French centres. 82 breast cancers concerning 75 women have been analyzed in terms of patient age, cancer type, interval between both cancers. It appears that radio-induced cancers exhibited significantly more aggressive characteristics. The screening of young women at risk is therefore recommended for an early diagnosis and treatment. Short communication

  2. Aggression in Women: Behavior, Brain and Hormones

    Directory of Open Access Journals (Sweden)

    Thomas F. Denson

    2018-05-01

    Full Text Available We review the literature on aggression in women with an emphasis on laboratory experimentation and hormonal and brain mechanisms. Women tend to engage in more indirect forms of aggression (e.g., spreading rumors than other types of aggression. In laboratory studies, women are less aggressive than men, but provocation attenuates this difference. In the real world, women are just as likely to aggress against their romantic partner as men are, but men cause more serious physical and psychological harm. A very small minority of women are also sexually violent. Women are susceptible to alcohol-related aggression, but this type of aggression may be limited to women high in trait aggression. Fear of being harmed is a robust inhibitor of direct aggression in women. There are too few studies and most are underpowered to detect unique neural mechanisms associated with aggression in women. Testosterone shows the same small, positive relationship with aggression in women as in men. The role of cortisol is unclear, although some evidence suggests that women who are high in testosterone and low in cortisol show heightened aggression. Under some circumstances, oxytocin may increase aggression by enhancing reactivity to provocation and simultaneously lowering perceptions of danger that normally inhibit many women from retaliating. There is some evidence that high levels of estradiol and progesterone are associated with low levels of aggression. We highlight that more gender-specific theory-driven hypothesis testing is needed with larger samples of women and aggression paradigms relevant to women.

  3. Social intelligence, empathy, and aggressive behavior: Is a stereotype of aggressive individual as socially incompetent inaccurate?

    OpenAIRE

    Marina Vidmar; Andreja Avsec

    2012-01-01

    In the present research, which was carried out on 187 high school students (86 girls and 101 boys), we examined to what extent different aspects of social intelligence contribute to indirect and direct aggression and to what extent empathy can act as a mitigator of aggression. We used The Aggression Questionnaire to measure physical aggression, IAS-A (which includes Social Exclusion, Use of Malicious Humour and Guilt Induction sub-scales) to measure indirect aggression, TSIS (which includes S...

  4. Enhanced sensitivity of postsynaptic serotonin-1A receptors in rats and mice with high trait aggression

    NARCIS (Netherlands)

    van der Vegt, BJ; de Boer, SF; Buwalda, B; de Ruiter, AJH; de Jong, JG; Koolhaas, JM

    2001-01-01

    Individual differences in aggressive behaviour have been linked to variability in central serotonergic activity, both in humans and animals. A previous experiment in mice, selectively bred for high or low levels of aggression, showed an up-regulation of postsynaptic serotonin-1A (5-HT1A) receptors,

  5. Sexual aggression when power is new: Effects of acute high power on chronically low-power individuals.

    Science.gov (United States)

    Williams, Melissa J; Gruenfeld, Deborah H; Guillory, Lucia E

    2017-02-01

    Previous theorists have characterized sexually aggressive behavior as an expression of power, yet evidence that power causes sexual aggression is mixed. We hypothesize that power can indeed create opportunities for sexual aggression-but that it is those who chronically experience low power who will choose to exploit such opportunities. Here, low-power men placed in a high-power role showed the most hostility in response to a denied opportunity with an attractive woman (Studies 1 and 2). Chronically low-power men and women given acute power were the most likely to say they would inappropriately pursue an unrequited workplace attraction (Studies 3 and 4). Finally, having power over an attractive woman increased harassment behavior among men with chronic low, but not high, power (Study 5). People who see themselves as chronically denied power appear to have a stronger desire to feel powerful and are more likely to use sexual aggression toward that end. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  6. Small Molecule Tyrosine Kinase Inhibitors of ErbB2/HER2/Neu in the Treatment of Aggressive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Richard L. Schroeder

    2014-09-01

    Full Text Available The human epidermal growth factor receptor 2 (HER2 is a member of the erbB class of tyrosine kinase receptors. These proteins are normally expressed at the surface of healthy cells and play critical roles in the signal transduction cascade in a myriad of biochemical pathways responsible for cell growth and differentiation. However, it is widely known that amplification and subsequent overexpression of the HER2 encoding oncogene results in unregulated cell proliferation in an aggressive form of breast cancer known as HER2-positive breast cancer. Existing therapies such as trastuzumab (Herceptin® and lapatinib (Tyverb/Tykerb®, a monoclonal antibody inhibitor and a dual EGFR/HER2 kinase inhibitor, respectively, are currently used in the treatment of HER2-positive cancers, although issues with high recurrence and acquired resistance still remain. Small molecule tyrosine kinase inhibitors provide attractive therapeutic targets, as they are able to block cell signaling associated with many of the proposed mechanisms for HER2 resistance. In this regard we aim to present a review on the available HER2 tyrosine kinase inhibitors, as well as those currently in development. The use of tyrosine kinase inhibitors as sequential or combinatorial therapeutic strategies with other HER family inhibitors is also discussed.

  7. The dopaminergic system and aggression in laying hens

    Science.gov (United States)

    The dopaminergic system regulates aggression in humans and other mammals. To investigate if birds with genetic propensity for high and low aggressiveness may exhibit distinctly different aggressive mediation via dopamine (DA) D1 and D2 receptor pathways, two high aggressive (DXL and LGPS) and one lo...

  8. The role of self-efficacy and assertiveness in aggression among high-school students in Isfahan.

    Science.gov (United States)

    Khademi Mofrad, S H; Mehrabi, T

    2015-01-01

    Background. Nowadays, one sixth of the world's population is represented by adolescents, nearly 1.2 billion people being of age 10-19. According to the 2011 census in Iran, the estimation of adolescent population was 12 million, which represents 16% of the Iran population. Undoubtedly, adolescence is the most dominant stage of life. During this period, adolescents face biological, cognitive, and emotional changes that may be accompanied by inappropriate behavioral responses such as aggression. Considering pressures of peer groups during adolescence, assertiveness has an important role as a social skill. It seems that the success of adolescents in dealing with these problems depends on their self-efficacy. This study was designed to explore the role of self-efficacy and assertiveness in aggression among high-school students. Material and methods. This cross-sectional and correlational study was conducted among 321 first grade high-school students during 2014 and 2015. Samples were extracted from six education and training regions by a multi-stage random sampling. In this study, the questionnaire included demographic, Rathus Assertiveness, self-efficacy for children and aggression data. Results. The results showed that there was a notable negative association between aggression and assertiveness (p assertiveness and self-efficacy resulted in a decrease of aggression. So, training was recommended to reinforce self-efficacy beliefs and assertiveness behaviors for mental health promotion.

  9. Social intelligence, empathy, and aggressive behavior: Is a stereotype of aggressive individual as socially incompetent inaccurate?

    Directory of Open Access Journals (Sweden)

    Marina Vidmar

    2012-03-01

    Full Text Available In the present research, which was carried out on 187 high school students (86 girls and 101 boys, we examined to what extent different aspects of social intelligence contribute to indirect and direct aggression and to what extent empathy can act as a mitigator of aggression. We used The Aggression Questionnaire to measure physical aggression, IAS-A (which includes Social Exclusion, Use of Malicious Humour and Guilt Induction sub-scales to measure indirect aggression, TSIS (which includes Social Information Processing, Social Skills and Social Awareness sub-scales to measure social intelligence and IRI (Perspective Taking and Empathic Concern sub-scales. The results confirmed our expectations that the cognitive aspect of empathy acts as an inhibitor of both direct and indirect aggression. The relationship between the ability of processing social information and indirect aggresssion was positive, whereas the relationship between social awareness and indirect aggression was negative, which shows that the relationships between various aspects of social intelligence and aggression are complex. People who have a high degree of social intelligence but do not have the tendency to take the other's perspective can use their abilities (especially social information processing to performn less evident and less prosecuted forms of aggressive behaviour which still have deleterious effects on interpersonal relationships.

  10. Autophagy Enhances the Aggressiveness of Human Colorectal Cancer Cells and Their Ability to Adapt to Apoptotic Stimulus

    International Nuclear Information System (INIS)

    Zheng, Hai-yang; Zhang, Xiao-yang; Wang, Xing-fen; Sun, Bao-cun

    2012-01-01

    To investigate LC3B-II and active caspase-3 expression in human colorectal cancer to elucidate the role of autophagy, and to explore the relationship of autophagy with apoptosis in human colorectal cancer. LC3B expression was detected by immunohistochemistry in 53 human colorectal cancer tissues and 20 normal colon tissues. The protein levels of LC3B-II and active caspase-3 were also determined by Western blot analysis in 23 human colorectal cancer tissues and 10 normal colon tissues. LC3B was expressed both in cancer cells and normal epithelial cells. LC3B expression in the peripheral area of cancer tissues was correlated with several clinicopathological factors, including tumor differentiation (P=0.002), growth pattern of the tumor margin (P=0.028), pN (P=0.002), pStage (P=0.032), as well as vessel and nerve plexus invasion (P=0.002). The protein level of LC3B-II in cancer tissue was significantly higher than in normal tissue (P=0.038), but the expression of active forms of procaspase-3 in cancer tissue was lower (P=0.041). There was a statistically significant positive correlation between the expression levels of LC3B-II and the active forms of procaspase-3 (r=0.537, P=0.008). Autophagy has a prosurvival role in human colorectal cancer. Autophagy enhances the aggressiveness of colorectal cancer cells and their ability to adapt to apoptotic stimulus

  11. Calcium Sensor, NCS-1, Promotes Tumor Aggressiveness and Predicts Patient Survival.

    Science.gov (United States)

    Moore, Lauren M; England, Allison; Ehrlich, Barbara E; Rimm, David L

    2017-07-01

    Neuronal Calcium Sensor 1 (NCS-1) is a multi-functional Ca 2+ -binding protein that affects a range of cellular processes beyond those related to neurons. Functional characterization of NCS-1 in neuronal model systems suggests that NCS-1 may influence oncogenic processes. To this end, the biological role of NCS-1 was investigated by altering its endogenous expression in MCF-7 and MB-231 breast cancer cells. Overexpression of NCS-1 resulted in a more aggressive tumor phenotype demonstrated by a marked increase in invasion and motility, and a decrease in cell-matrix adhesion to collagen IV. Overexpression of NCS-1 was also shown to increase the efficacy of paclitaxel-induced cell death in a manner that was independent of cellular proliferation. To determine the association between NCS-1 and clinical outcome, NCS-1 expression was measured in two independent breast cancer cohorts by the Automated Quantitative Analysis method of quantitative immunofluorescence. Elevated levels of NCS-1 were significantly correlated with shorter survival rates. Furthermore, multivariate analysis demonstrated that NCS-1 status was prognostic, independent of estrogen receptor, progesterone receptor, HER2, and lymph node status. These findings indicate that NCS-1 plays a role in the aggressive behavior of a subset of breast cancers and has therapeutic or biomarker potential. Implications: NCS-1, a calcium-binding protein, is associated with clinicopathologic features of aggressiveness in breast cancer cells and worse outcome in two breast cancer patient cohorts. Mol Cancer Res; 15(7); 942-52. ©2017 AACR . ©2017 American Association for Cancer Research.

  12. Bystander Action in Situations of Dating and Sexual Aggression: A Mixed Methodological Study of High School Youth.

    Science.gov (United States)

    Edwards, Katie M; Rodenhizer-Stämpfli, Kara Anne; Eckstein, Robert P

    2015-12-01

    Bystander action is a critical component of dating and sexual aggression prevention; however, little is known about barriers and facilitators of bystander action among high school youth and in what situations youth are willing to engage in bystander action. The current study examined bystander action in situations of dating and sexual aggression using a mixed methodological design. Participants included primarily Caucasian (83.0%, n = 181) male (54.6%, n = 119) and female (44.5%, n = 97) high school youth (N = 218). Most (93.6%) students had the opportunity to take action during the past year in situations of dating or sexual aggression; being female and histories of dating and sexual aggression related to bystander action. Thematic analysis of the focus group data identified barriers (e.g., the aggression not meeting a certain threshold, anticipated negative consequences) to bystander action, as well as insight on promising forms of action (e.g., verbally telling the perpetrator to stop, getting a teacher); problematic intervention methods (e.g., threatening or using physical violence to stop the perpetrator) were also noted. Implications for programming are discussed.

  13. Cyclical thrombocytosis, acquired von Willebrand syndrome and aggressive non-melanoma skin cancers are common in patients with Philadelphia-negative myeloproliferative neoplasms treated with hydroxyurea.

    Science.gov (United States)

    Verner, Emma; Forsyth, Cecily; Grigg, Andrew

    2014-05-01

    Abstract Cyclical thrombocytosis, acquired von Willebrand syndrome, aggressive non-melanoma skin cancers and other hydroxyurea complications have been reported in Philadelphia-negative myeloproliferative neoplasms (MPNs), but their incidence and clinical consequences have not been defined in a large cohort of patients. We conducted a retrospective analysis of 188 consecutive patients with MPNs specifically addressing the incidence of these complications. Cyclical thrombocytosis was documented in 29 patients (15%), the majority of whom were receiving hydroxyurea. Acquired von Willebrand syndrome was identified in 17 of the 84 screened patients (20%), but was not associated with any major bleeding complications. Non-melanoma skin cancers were reported in 51 patients (27%). Hydroxyurea-related fever occurred in nine of 149 patients (6%) who received hydroxyurea. Seventy-three patients (39%) experienced a total of 98 major thrombotic events, with the majority of these occurring prior to or within 3 months of the diagnosis. Cyclical thrombocytosis, acquired von Willebrand syndrome, aggressive non-melanoma skin cancers and other hydroxyurea-related complications are not infrequent in MPNs and have important clinical consequences for management.

  14. Mid-face location of primary basal cell carcinoma related to cancer aggressivity

    Directory of Open Access Journals (Sweden)

    Prasetyadi Mawardi

    2016-08-01

    Full Text Available Objective: To study the aggressiveness of basal cell carcinoma (BCC on the mid-face location. Methods: A total of 30 patients were diagnosed using specimen biopsy with hematoxylineosin stain at Moewardi Public Hospital in Surakarta, Central Java, Indonesia. The age, gender distribution, site of the lesion, as well as clinic-pathological appearance were analyzed. Results: There were 30 patients consisting of 46.7% males and 53.3% females with ages ranging from 33 to 91 years old and with the most common occupation, such as farmers (53.6% and housewives (26.7%. Morpheaform subtypes BCC were more frequent than other types. Based on the predilection, most of the BCC were found to be in the mid-face (76.7% and using determined criteria of histopathological examination, the aggressive appearance was 77% and non-aggressive BCC was 23%. The BCC on the mid-face location was more aggressive than the other sites (P < 0.05. Conclusions: BCC is the most common skin tumor in humans with rare metastases, which might cause significant damage due to its local recurrences and aggressiveness. BCC on the mid-face is significantly more aggressive than that on the other predilection sites.

  15. The Very High Risk Prostate Cancer – a Contemporary Update

    Science.gov (United States)

    Mano, Roy; Eastham, James; Yossepowitch, Ofer

    2017-01-01

    Background Treatment of high-risk prostate cancer has evolved considerably over the past two decades, yet patients with very high-risk features may still experience poor outcome despite aggressive therapy. We review the contemporary literature focusing on current definitions, role of modern imaging and treatment alternatives in very high-risk prostate cancer. Methods We searched the MEDLINE database for all clinical trials or practice guidelines published in English between 2000 – 2016 with the following search terms: ‘prostatic neoplasms’ (MeSH Terms) AND (‘high risk’ (keyword) OR ‘locally advanced’ (keyword) OR ‘node positive’ (keyword)). Abstracts pertaining to very high-risk prostate cancer were evaluated and 40 pertinent studies served as the basis for this review. Results The term ‘very’ high-risk prostate cancer remains ill defined. The EAU and NCCN guidelines provide the only available definitions, categorizing those with clinical stage T3-4 or minimal nodal involvement as very-high risk irrespective of PSA level or biopsy Gleason score. Modern imaging with mpMRI and PET-PSMA scans plays a role in pretreatment assessment. Local definitive therapy by external beam radiation combined with androgen deprivation is supported by several randomized clinical trials whereas the role of surgery in the very high-risk setting combined with adjuvant radiation/ androgen deprivation therapy is emerging. Growing evidence suggest neoadjuvant taxane based chemotherapy in the context of a multimodal approach may be beneficial. Conclusions Men with very high-risk tumors may benefit from local definitive treatment in the setting of a multimodal regimen, offering local control and possibly cure in well selected patients. Further studies are necessary to better characterize the ‘very’ high-risk category and determine the optimal therapy for the individual patient. PMID:27618950

  16. EP4 as a Therapeutic Target for Aggressive Human Breast Cancer

    Directory of Open Access Journals (Sweden)

    Mousumi Majumder

    2018-03-01

    selective EP4 antagonists (EP4A could mitigate all of these events tested with cells in vitro as well as in vivo in syngeneic COX-2 expressing mammary cancer bearing mice or immune-deficient mice bearing COX-2 over-expressing human breast cancer xenografts. We suggest that EP4A can avoid thrombo-embolic side effects of long term use of COX-2 inhibitors by sparing cardio-protective roles of PGI2 via IP receptor activation or PGE2 via EP3 receptor activation. Furthermore, we identified two COX-2/EP4 induced oncogenic and SLC-stimulating microRNAs—miR526b and miR655, one of which (miR655 appears to be a potential blood biomarker in breast cancer patients for monitoring SLC-ablative therapies, such as with EP4A. We suggest that EP4A will likely produce the highest benefit in aggressive breast cancers, such as COX-2 expressing triple-negative breast cancers, when combined with other newer agents, such as inhibitors of programmed cell death (PD-1 or PD-L1.

  17. Partner Aggression in High-Risk Families From Birth to Age 3: Associations With Harsh Parenting and Child Maladjustment

    Science.gov (United States)

    Graham, Alice M.; Kim, Hyoun K.; Fisher, Philip A.

    2012-01-01

    Aggression between partners represents a potential guiding force in family dynamics. However, research examining the influence of partner aggression (physically and psychologically aggressive acts by both partners) on harsh parenting and young child adjustment has been limited by a frequent focus on low risk samples and by the examination of partner aggression at a single time point. Especially in the context of multiple risk factors and around transitions such as childbirth, partner aggression might be better understood as a dynamic process. In the present study, longitudinal trajectories of partner aggression from birth to age 3 years in a large, high-risk, and ethnically diverse sample (N = 461) were examined. Specific risk factors were tested as predictors of aggression over time, and the longitudinal effects of partner aggression on maternal harsh parenting and child maladjustment were examined. Partner aggression decreased over time, with higher maternal depression and lower maternal age predicting greater decreases in partner aggression. While taking into account contextual and psychosocial risk factors, higher partner aggression measured at birth and a smaller decrease over time independently predicted higher levels of maternal harsh parenting at age 3 years. Initial level of partner aggression and change over time predicted child maladjustment indirectly (via maternal harsh parenting). The implications of understanding change in partner aggression over time as a path to harsh parenting and young children's maladjustment in the context of multiple risk factors are discussed. PMID:22201248

  18. A cross-lagged structural equation model of relational aggression, physical aggression, and peer status in a Chinese culture.

    Science.gov (United States)

    Tseng, Wan-Ling; Banny, Adrienne M; Kawabata, Yoshito; Crick, Nicki R; Gau, Susan Shur-Fen

    2013-01-01

    This short-term longitudinal study examined the associations among relational aggression, physical aggression, and peer status (i.e., acceptance, rejection, and perceived popularity) across three time points, six months apart, in a Taiwanese sample. Participants were 198 fifth grade students (94 girls and 104 boys; Mean age = 10.35 years) from Taipei, Taiwan. Study variables were assessed using peer nomination procedure. Results from the cross-lagged structural equation models demonstrated that there were longitudinal associations between relational aggression and each of the peer status constructs while only one longitudinal association was found for physical aggression such that physical aggression positively predicted subsequent peer rejection. The longitudinal associations did not vary with gender. Results also showed high stabilities of relational aggression, physical aggression, and the three peer status constructs over 1 year as well as high concurrent association between relational and physical aggression. In addition, relational aggression and physical aggression were concurrently related to less acceptance, more rejection, and less perceived popularity, especially at the outset of the study. Findings of this study demonstrated both similarities and differences in relation to previous literature in primarily Western cultures. This study also highlights the bidirectional and complex nature of the association between aggression and peer status, which appears to depend on the form of aggression and on the particular indicator of peer status under study. Copyright © 2013 Wiley Periodicals, Inc.

  19. MMP1, MMP9, and COX2 Expressions in Promonocytes Are Induced by Breast Cancer Cells and Correlate with Collagen Degradation, Transformation-Like Morphological Changes in MCF-10A Acini, and Tumor Aggressiveness

    Directory of Open Access Journals (Sweden)

    G. K. Chimal-Ramírez

    2013-01-01

    Full Text Available Tumor-associated immune cells often lack immune effector activities, and instead they present protumoral functions. To understand how tumors promote this immunological switch, invasive and noninvasive breast cancer cell (BRC lines were cocultured with a promonocytic cell line in a Matrigel-based 3D system. We hypothesized that if communication exists between tumor and immune cells, coculturing would result in augmented expression of genes associated with tumor malignancy. Upregulation of proteases MMP1 and MMP9 and inflammatory COX2 genes was found likely in response to soluble factors. Interestingly, changes were more apparent in promonocytes and correlated with the aggressiveness of the BRC line. Increased gene expression was confirmed by collagen degradation assays and immunocytochemistry of prostaglandin 2, a product of COX2 activity. Untransformed MCF-10A cells were then used as a sensor of soluble factors with transformation-like capabilities, finding that acini formed in the presence of supernatants of the highly aggressive BRC/promonocyte cocultures often exhibited total loss of the normal architecture. These data support that tumor cells can modify immune cell gene expression and tumor aggressiveness may importantly reside in this capacity. Modeling interactions in the tumor stroma will allow the identification of genes useful as cancer prognostic markers and therapy targets.

  20. Risk stratification of patients with locally aggressive differentiated thyroid cancer. Results of the MSDS trial

    International Nuclear Information System (INIS)

    Riemann, B.; Kraemer, J.A.; Schober, O.; Schmid, K.W.; Dralle, H.; Dietlein, M.; Schicha, H.; Sauerland, C.; Frankewitsch, T.

    2010-01-01

    The Multicentre Study Differentiated Thyroid Cancer (MSDS) collective represents a well defined group of patients with locally aggressive thyroid carcinomas (pT4; AJCC/UICC 1997). The aim of the present study was to compare the survival of patients with minimum and extensive extrathyroidal growth according to the new AJCC/UICC TNM staging system 2009. Patients, methods: The follow-up data of 347 patients were analysed. Patients were reclassified according to the current AJCC/UICC 2009 classification. The event-free and overall survival was evaluated using Kaplan-Meier analysis. In addition, postoperative complications and status of disease were documented. Results: 327 patients were assigned to stage pT3 and 20 patients to stage pT4a, respectively. Median follow-up was 6.1 years (range 0.04-9.8 years). 92.5% of patients reached complete remission. There were 7.8% recurrences in the thyroid bed, in locoregional lymph nodes and/or in distant sites. The overall survival was >98% both in pT3 and pT4a patients (p = n. s.). In contrast, the event-free survival was significantly less favourable in pT4a patients (p < 0.001). Using multivariate analysis the following parameters were significant predictors of event-free survival: histological tumour type, degree of extrathyroidal extension and nodal metastasis (p < 0.05). Conclusions: The MSDS patients with locally aggressive differentiated thyroid cancer showed an excellent overall survival during a median follow-up of 6.1 years. According to the current AJCC/UICC 2009 classification, pT3 patients with minimal extrathyroidal extension revealed a significantly better event-free survival than pT4a patients with extensive extrathyroidal growth. (orig.)

  1. When do normative beliefs about aggression predict aggressive behavior? An application of I3 theory.

    Science.gov (United States)

    Li, Jian-Bin; Nie, Yan-Gang; Boardley, Ian D; Dou, Kai; Situ, Qiao-Min

    2015-01-01

    I(3) theory assumes that aggressive behavior is dependent on three orthogonal processes (i.e., Instigator, Impellance, and Inhibition). Previous studies showed that Impellance (trait aggressiveness, retaliation tendencies) better predicted aggression when Instigator was strong and Inhibition was weak. In the current study, we predicted that another Impellance (i.e., normative beliefs about aggression) might predict aggression when Instigator was absent and Inhibition was high (i.e., the perfect calm proposition). In two experiments, participants first completed the normative beliefs about aggression questionnaire. Two weeks later, participants' self-control resources were manipulated either using the Stroop task (study 1, N = 148) or through an "e-crossing" task (study 2, N = 180). Afterwards, with or without being provoked, participants played a game with an ostensible partner where they had a chance to aggress against them. Study 1 found that normative beliefs about aggression negatively and significantly predicted aggressive behavior only when provocation was absent and self-control resources were not depleted. In Study 2, normative beliefs about aggression negatively predicted aggressive behavior at marginal significance level only in the "no-provocation and no-depletion" condition. In conclusion, the current study provides partial support for the perfect calm proposition and I(3) theory. © 2015 Wiley Periodicals, Inc.

  2. Partner aggression among men and women in substance use disorder treatment: correlates of psychological and physical aggression and injury.

    Science.gov (United States)

    Chermack, Stephen T; Murray, Regan L; Walton, Maureen A; Booth, Brenda A; Wryobeck, John; Blow, Frederic C

    2008-11-01

    This study examined intimate partner aggression in a sample of 489 participants enrolled in substance use disorder treatment, and expands on prior research by including measures of various forms of aggression, a mixed gender sample (76% men, 24% women), and measurement of several potential risk domains. Aggression measures included both participant-partner and partner-to-participant psychological aggression, physical aggression and injury. Analyses focused on the role of distal and proximal risk factors, including demographics, history of childhood physical and sexual abuse, and family history of problems with alcohol, drugs and depression, as well as recent substance use and symptoms of depression. Overall rates of participant-partner psychological aggression (77%), physical aggression (54%) and injuring partners (33%) were high, as were rates of partner-to-participant psychological aggression (73%), physical aggression (51%), and injury (33%). Several distal (family history variables, physical abuse) and proximal factors (binge drinking, several different drugs, depressive symptoms) were bivariately related to most of the aggression measures. However, according to multivariate analyses predicting aggression and injury measures, binge drinking and cocaine use were the drugs significantly associated with most measures, depression symptoms also were related to most aggression and injury measures, and a history of reported childhood physical abuse was related to all frequency of aggression and injury measures among those reporting such behaviors. Overall, the high rates of aggression among both men and women observed in this study further illustrate the need for interventions targeting substance use and aggression, and for further research regarding the inter-relationships among substance, aggression and depressive symptoms.

  3. Aggression and anxiety: social context and neurobiological links

    Directory of Open Access Journals (Sweden)

    Inga D Neumann

    2010-03-01

    Full Text Available Psychopathologies such as anxiety- and depression-related disorders are often characterized by impaired social behaviours including excessive aggression and violence. Excessive aggression and violence likely develop as a consequence of generally disturbed emotional regulation, such as abnormally high or low levels of anxiety. This suggests an overlap between brain circuitries and neurochemical systems regulating aggression and anxiety. In this review, we will discuss different forms of male aggression, rodent models of excessive aggression, and neurobiological mechanisms underlying male aggression in the context of anxiety. We will summarize our attempts to establish an animal model of high and abnormal aggression using rats selected for high (HAB versus low (LAB anxiety-related behaviour. Briefly, male LAB rats and, to a lesser extent, male HAB rats show high and abnormal forms of aggression compared with non-selected (NAB rats, making them a suitable animal model for studying excessive aggression in the context of extremes in innate anxiety. In addition, we will discuss differences in the activity of the hypothalamic-pituitary-adrenal axis, brain arginine vasopressin, and the serotonin systems, among others, which contribute to the distinct behavioural phenotypes related to aggression and anxiety. Further investigation of the neurobiological systems in animals with distinct anxiety phenotypes might provide valuable information about the link between excessive aggression and disturbed emotional regulation, which is essential for understanding the social and emotional deficits that are characteristic of many human psychiatric disorders.

  4. Aggression in children with behavioural/emotional difficulties: seeing aggression on television and video games.

    Science.gov (United States)

    Mitrofan, Oana; Paul, Moli; Weich, Scott; Spencer, Nicholas

    2014-11-18

    Mental health professionals are often asked to give advice about managing children's aggression. Good quality evidence on contributory environmental factors such as seeing aggression on television and in video games is relatively lacking, although societal and professional concerns are high. This study investigated possible associations between seeing aggression in such media and the aggressive behaviour of children attending specialist outpatient child and adolescent mental health services (CAMHS). In this mixed methods study, forty-seven British children aged 7-11 years with behavioural/emotional difficulties attending CAMHS and their carers participated in a survey; twenty purposively-selected children and a parent/carer of theirs participated in a qualitative study, involving semi-structured interviews, analysed using the Framework Analysis Approach; findings were integrated. Children attending CAMHS exhibit clinically significant aggression, of varying types and frequency. They see aggression in multiple real and virtual settings. Verbal aggression was often seen, frequently exhibited and strongly associated with poor peer relationships and low prosocial behaviour. Children did not think seeing aggression influences their own behaviour but believed it influences others. Carers regarded aggression as resulting from a combination of inner and environmental factors and seeing aggression in real-life as having more impact than television/video games. There is yet no definitive evidence for or against a direct relationship between aggression seen in the media and aggression in children with behavioural/emotional difficulties. Future research should take an ecological perspective, investigating individual, developmental and environmental factors. Carers, professional organisations and policy makers should address aggression seen in all relevant area of children's lives, primarily real-life and secondly virtual environments.

  5. Callous-Unemotional Features, Behavioral Inhibition, and Parenting: Independent Predictors of Aggression in a High-Risk Preschool Sample

    Science.gov (United States)

    Kimonis, Eva R.; Frick, Paul J.; Boris, Neil W.; Smyke, Anna T.; Cornell, Amy H.; Farrell, Jamie M.; Zeanah, Charles H.

    2006-01-01

    A behaviorally-uninhibited temperament, callous-unemotional (CU) features, and harsh parenting have been associated with specific patterns of aggressive behavior in older children and adolescents. We tested the additive and interactive effects of these factors in predicting different types of aggressive behavior in a high-risk preschool sample.…

  6. A preliminary investigation of a new pictorial method of measuring aggression-supportive cognition among young aggressive males.

    Science.gov (United States)

    Hutchings, Jade N; Gannon, Theresa A; Gilchrist, Elizabeth

    2010-04-01

    A new pictorial assessment was developed to measure aggression-supportive cognitions among young aggressive male students. The assessment was comprised of 17 watercolor ambiguous sketches that could be interpreted in either an aggressive or a benign manner (e.g., two young people facing each other with their arms folded). The results showed that high trait aggressive male students were more likely to make hostile attributions of the pictures, providing significantly more themes of entitlement and power in the stories they generated about the pictures. Aggressive male students also endorsed significantly more aggression-supportive cognitions on a self-report measure and provided some supporting qualitative accounts of physically aggressive encounters. The results of this study are discussed and evaluated with reference to future work with young violent adolescents.

  7. Total or partial vertebrectomy for lung cancer invading the spine

    Directory of Open Access Journals (Sweden)

    Soichi Oka

    2016-12-01

    Conclusions: In our experience, Lung cancer surgery combined with vertebrectomy is highly aggressive surgery associated with high morbidity. But, this procedure is a promising treatment option for selected patients, for example N0M0 disease with lung cancer invading the spine.

  8. Aggression

    NARCIS (Netherlands)

    Tonnaer, F.; Cima, M.; Arntz, A.R.; Cima, M.

    2016-01-01

    Aggression, violence and deviant behavior are terms frequently used interchangeable, but relate to different theoretical concepts. Therefore, this chapter starts with a definition of aggression. Furthermore, several theories regarding the development of aggression will be presented. According to

  9. Partner aggression in high-risk families from birth to age 3 years: associations with harsh parenting and child maladjustment.

    Science.gov (United States)

    Graham, Alice M; Kim, Hyoun K; Fisher, Philip A

    2012-02-01

    Aggression between partners represents a potential guiding force in family dynamics. However, research examining the influence of partner aggression (physically and psychologically aggressive acts by both partners) on harsh parenting and young child adjustment has been limited by a frequent focus on low-risk samples and by the examination of partner aggression at a single time point. Especially in the context of multiple risk factors and around transitions such as childbirth, partner aggression might be better understood as a dynamic process. In the present study, longitudinal trajectories of partner aggression from birth to age 3 years in a large, high-risk, and ethnically diverse sample (N = 461) were examined. Specific risk factors were tested as predictors of aggression over time, and the longitudinal effects of partner aggression on maternal harsh parenting and child maladjustment were examined. Partner aggression decreased over time, with higher maternal depression and lower maternal age predicting greater decreases in partner aggression. While taking into account contextual and psychosocial risk factors, higher partner aggression measured at birth and a smaller decrease over time independently predicted higher levels of maternal harsh parenting at age 3 years. Initial level of partner aggression and change over time predicted child maladjustment indirectly (via maternal harsh parenting). The implications of understanding change in partner aggression over time as a path to harsh parenting and young children's maladjustment in the context of multiple risk factors are discussed.

  10. Thyroid cancer in children in Belarus

    International Nuclear Information System (INIS)

    Demidchik, E.P.; Drobyshevskaya, I.M.; Cherstvoy, E.D.; Astakhova, L.N.; Vorontsova, T.V.; Okeanov, A.E.; Germenchuk, M.

    1996-01-01

    Pediatric thyroid cancer was diagnosed in 390 patients in Belarus after the Chernobyl accident. The morbidity rates increased by 55.7 times as compared with the 10 year pre-accident period. Thyroid cancer in children is highly aggressive disease accompanied by surrounding tissues and metastatic involvement of lymph nodes

  11. The Potential of Targeting Ribosome Biogenesis in High-Grade Serous Ovarian Cancer

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    Shunfei Yan

    2017-01-01

    Full Text Available Overall survival for patients with ovarian cancer (OC has shown little improvement for decades meaning new therapeutic options are critical. OC comprises multiple histological subtypes, of which the most common and aggressive subtype is high-grade serous ovarian cancer (HGSOC. HGSOC is characterized by genomic structural variations with relatively few recurrent somatic mutations or dominantly acting oncogenes that can be targeted for the development of novel therapies. However, deregulation of pathways controlling homologous recombination (HR and ribosome biogenesis has been observed in a high proportion of HGSOC, raising the possibility that targeting these basic cellular processes may provide improved patient outcomes. The poly (ADP-ribose polymerase (PARP inhibitor olaparib has been approved to treat women with defects in HR due to germline BRCA mutations. Recent evidence demonstrated the efficacy of targeting ribosome biogenesis with the specific inhibitor of ribosomal RNA synthesis, CX-5461 in v-myc avian myelocytomatosis viral oncogene homolog (MYC-driven haematological and prostate cancers. CX-5461 has now progressed to a phase I clinical trial in patients with haematological malignancies and phase I/II trial in breast cancer. Here we review the currently available targeted therapies for HGSOC and discuss the potential of targeting ribosome biogenesis as a novel therapeutic approach against HGSOC.

  12. Impulsivity, aggression and brain structure in high and low lethality suicide attempters with borderline personality disorder.

    Science.gov (United States)

    Soloff, Paul; White, Richard; Diwadkar, Vaibhav A

    2014-06-30

    Impulsivity and aggressiveness are trait dispositions associated with the vulnerability to suicidal behavior across diagnoses. They are associated with structural and functional abnormalities in brain networks involved in regulation of mood, impulse and behavior. They are also core characteristics of borderline personality disorder (BPD), a disorder defined, in part, by recurrent suicidal behavior. We assessed the relationships between personality traits, brain structure and lethality of suicide attempts in 51 BPD attempters using multiple regression analyses on structural MRI data. BPD was diagnosed by the Diagnostic Interview for Borderline Patients-revised, impulsivity by the Barratt Impulsiveness Scale (BIS), aggression by the Brown-Goodwin Lifetime History of Aggression (LHA), and high lethality by a score of 4 or more on the Lethality Rating Scale (LRS). Sixteen High Lethality attempters were compared to 35 Low Lethality attempters, with no significant differences noted in gender, co-morbidity, childhood abuse, BIS or LHA scores. Degree of medical lethality (LRS) was negatively related to gray matter volumes across multiple fronto-temporal-limbic regions. Effects of impulsivity and aggression on gray matter volumes discriminated High from Low Lethality attempters and differed markedly within lethality groups. Lethality of suicide attempts in BPD may be related to the mediation of these personality traits by specific neural networks. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Predictive value of four kallikrein markers for pathologically insignificant compared with aggressive prostate cancer in radical prostatectomy specimens: results from the European Randomized Study of Screening for Prostate Cancer section Rotterdam.

    Science.gov (United States)

    Carlsson, Sigrid; Maschino, Alexandra; Schröder, Fritz; Bangma, Chris; Steyerberg, Ewout W; van der Kwast, Theo; van Leenders, Geert; Vickers, Andrew; Lilja, Hans; Roobol, Monique J

    2013-11-01

    Treatment decisions can be difficult in men with low-risk prostate cancer (PCa). To evaluate the ability of a panel of four kallikrein markers in blood-total prostate-specific antigen (PSA), free PSA, intact PSA, and kallikrein-related peptidase 2-to distinguish between pathologically insignificant and aggressive disease on pathologic examination of radical prostatectomy (RP) specimens as well as to calculate the number of avoidable surgeries. The cohort comprised 392 screened men participating in rounds 1 and 2 of the Rotterdam arm of the European Randomized Study of Screening for Prostate Cancer. Patients were diagnosed with PCa because of an elevated PSA ≥3.0 ng/ml and were treated with RP between 1994 and 2004. We calculated the accuracy (area under the curve [AUC]) of statistical models to predict pathologically aggressive PCa (pT3-T4, extracapsular extension, tumor volume >0.5cm(3), or any Gleason grade ≥4) based on clinical predictors (age, stage, PSA, biopsy findings) with and without levels of four kallikrein markers in blood. A total of 261 patients (67%) had significant disease on pathologic evaluation of the RP specimen. While the clinical model had good accuracy in predicting aggressive disease, reflected in a corrected AUC of 0.81, the four kallikrein markers enhanced the base model, with an AUC of 0.84 (p limitation of the present study is that clinicians may be hesitant to make recommendations against active treatment on the basis of a statistical model. Our study provided proof of principle that predictions based on levels of four kallikrein markers in blood distinguish between pathologically insignificant and aggressive disease after RP with good accuracy. In the future, clinical use of the model could potentially reduce rates of immediate unnecessary active treatment. Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  14. Evaluation of the normal-to-diseased apparent diffusion coefficient ratio as an indicator of prostate cancer aggressiveness.

    Science.gov (United States)

    Lebovici, Andrei; Sfrangeu, Silviu A; Feier, Diana; Caraiani, Cosmin; Lucan, Ciprian; Suciu, Mihai; Elec, Florin; Iacob, Gheorghita; Buruian, Mircea

    2014-05-10

    We tested the feasibility of a simple method for assessment of prostate cancer (PCa) aggressiveness using diffusion-weighted magnetic resonance imaging (MRI) to calculate apparent diffusion coefficient (ADC) ratios between prostate cancer and healthy prostatic tissue. The requirement for institutional review board approval was waived. A set of 20 standardized core transperineal saturation biopsy specimens served as the reference standard for placement of regions of interest on ADC maps in tumorous and normal prostatic tissue of 22 men with PCa (median Gleason score: 7; range, 6-9). A total of 128 positive sectors were included for evaluation. Two diagnostic ratios were computed between tumor ADCs and normal sector ADCs: the ADC peripheral ratio (the ratio between tumor ADC and normal peripheral zone tissue, ADC-PR), and the ADC central ratio (the ratio between tumor ADC and normal central zone tissue, ADC-CR). The performance of the two ratios in detecting high-risk tumor foci (Gleason 8 and 9) was assessed using the area under the receiver operating characteristic curve (AUC). Both ADC ratios presented significantly lower values in high-risk tumors (0.48 ± 0.13 for ADC-CR and 0.40 ± 0.09 for ADC-PR) compared with low-risk tumors (0.66 ± 0.17 for ADC-CR and 0.54 ± 0.09 for ADC-PR) (p performance (ADC-CR AUC = 0.77, sensitivity = 82.2%, specificity = 66.7% and ADC-PR AUC = 0.90, sensitivity = 93.7%, specificity = 80%) than stand-alone tumor ADCs (AUC of 0.75, sensitivity = 72.7%, specificity = 70.6%) for identifying high-risk lesions. The ADC ratio as an intrapatient-normalized diagnostic tool may be better in detecting high-grade lesions compared with analysis based on tumor ADCs alone, and may reduce the rate of biopsies.

  15. Evaluation of the normal-to-diseased apparent diffusion coefficient ratio as an indicator of prostate cancer aggressiveness

    International Nuclear Information System (INIS)

    Lebovici, Andrei; Sfrangeu, Silviu A; Feier, Diana; Caraiani, Cosmin; Lucan, Ciprian; Suciu, Mihai; Elec, Florin; Iacob, Gheorghita; Buruian, Mircea

    2014-01-01

    We tested the feasibility of a simple method for assessment of prostate cancer (PCa) aggressiveness using diffusion-weighted magnetic resonance imaging (MRI) to calculate apparent diffusion coefficient (ADC) ratios between prostate cancer and healthy prostatic tissue. The requirement for institutional review board approval was waived. A set of 20 standardized core transperineal saturation biopsy specimens served as the reference standard for placement of regions of interest on ADC maps in tumorous and normal prostatic tissue of 22 men with PCa (median Gleason score: 7; range, 6–9). A total of 128 positive sectors were included for evaluation. Two diagnostic ratios were computed between tumor ADCs and normal sector ADCs: the ADC peripheral ratio (the ratio between tumor ADC and normal peripheral zone tissue, ADC-PR), and the ADC central ratio (the ratio between tumor ADC and normal central zone tissue, ADC-CR). The performance of the two ratios in detecting high-risk tumor foci (Gleason 8 and 9) was assessed using the area under the receiver operating characteristic curve (AUC). Both ADC ratios presented significantly lower values in high-risk tumors (0.48 ± 0.13 for ADC-CR and 0.40 ± 0.09 for ADC-PR) compared with low-risk tumors (0.66 ± 0.17 for ADC-CR and 0.54 ± 0.09 for ADC-PR) (p < 0.001) and had better diagnostic performance (ADC-CR AUC = 0.77, sensitivity = 82.2%, specificity = 66.7% and ADC-PR AUC = 0.90, sensitivity = 93.7%, specificity = 80%) than stand-alone tumor ADCs (AUC of 0.75, sensitivity = 72.7%, specificity = 70.6%) for identifying high-risk lesions. The ADC ratio as an intrapatient-normalized diagnostic tool may be better in detecting high-grade lesions compared with analysis based on tumor ADCs alone, and may reduce the rate of biopsies

  16. Aggressive behavior prevention in a dance duet

    Directory of Open Access Journals (Sweden)

    Olena Gant

    2017-10-01

    Full Text Available Purpose: to study the features of aggression and the main directions of prevention of aggressive forms of behavior, among athletes engaged in sports dancing in the preliminary basic training. Material & Methods: analysis of scientific and methodological literature, "Personal aggressiveness and conflictness". Results: a theoretical analysis of the problem of aggressive behavior in sports dance duets. Level of aggressiveness of athletes of sports dances at the stage of preliminary basic training is determined. Reasons for the formation of aggressive behavior among young athletes are revealed. Areas of preventive and psychocorrectional work with aggressive athletes are singled out. Conclusion: a high level of aggression was detected in 19 (31,67% of the study participants. Determinants of aggressive behavior in sport ballroom pair appear particularly family upbringing style and pedagogical activity of the trainer. Correction of aggressive behavior of young athletes should have a complex systemic character and take into account the main characterological features of aggressive athletes.

  17. Psychological features of aggression in adolescence

    Directory of Open Access Journals (Sweden)

    .O. Kuznetsova

    2014-08-01

    Full Text Available We present the results of empirical study of the psychological characteristics of aggression and frustration response in adolescents with different types of socialization. We describe the qualitative and quantitative aspects of aggression in adolescence. We show the nature of the relationship of a aggressiveness features with type of socialization in adolescents. The described study involved 125 male adolescents aged 13-14 years, enrolled in the VIII grade (56 cadets and 69 students. We used methods of testing, survey, subjective scaling. In cadets, we found elevated rates of aggression and hostility, the prevalence of physical aggression, high scores on Irritation, Verbal aggression and Suspicion, as well as the prevalence in situations of frustration of extrapunitive reactions with “fixation on self-defense”. In the group of students of secondary school, the levels of aggression and hostility an on upper limit of test norms, impunitive reactions, indirect aggression, guilt, constructive reaction with “fixation on meeting needs” prevail.

  18. Does Humor Explain Why Relationally Aggressive Adolescents Are Popular?

    Science.gov (United States)

    Bowker, Julie C.; Etkin, Rebecca G.

    2013-01-01

    The association between relational aggression and popularity during early adolescence is well established. Yet, little is known about why, exactly, relationally aggressive young adolescents are able to achieve and maintain high popular status among peers. The present study investigated the mediating role of humor in the association between relational aggression and popularity during early adolescence. Also considered was whether the association between relational aggression and humor varies according to adolescents’ gender and their friends’ levels of relational aggression. Participants were 265 sixth-grade students (48% female; 41% racial/ethnic minority; Mage = 12.04 years) who completed peer nomination and friendship measures in their classrooms at two time points (Wave 1: February; Wave 2: May). The results indicated that Wave 1 relational aggression was related to Wave 1 and 2 popularity indirectly through Wave 1 humor, after accounting for the effects of Wave 1 physical aggression, ethnicity, and gender. Additional analyses showed that relational aggression and humor were related significantly only for boys and for young adolescents with highly relationally aggressive friends. The results support the need for further research on humor and aggression during early adolescence and other mechanisms by which relationally aggressive youth achieve high popular status. PMID:24136377

  19. Adolescents’ Aggression to Parents: Longitudinal Links with Parents’ Physical Aggression

    Science.gov (United States)

    Margolin, Gayla; Baucom, Brian R.

    2014-01-01

    Purpose To investigate whether parents’ previous physical aggression (PPA) exhibited during early adolescence is associated with adolescents’ subsequent parent-directed aggression even beyond parents’ concurrent physical aggression (CPA); to investigate whether adolescents’ emotion dysregulation and attitudes condoning child-to-parent aggression moderate associations. Methods Adolescents (N = 93) and their parents participated in a prospective, longitudinal study. Adolescents and parents reported at waves 1–3 on four types of parents’ PPA (mother-to-adolescent, father-to-adolescent, mother-to-father, father-to-mother). Wave 3 assessments also included adolescents’ emotion dysregulation, attitudes condoning aggression, and externalizing behaviors. At waves 4 and 5, adolescents and parents reported on adolescents’ parent-directed physical aggression, property damage, and verbal aggression, and on parents’ CPA Results Parents’ PPA emerged as a significant indicator of adolescents’ parent-directed physical aggression (odds ratio [OR]: 1.25, 95% confidence interval [CI]: 1.0–1.55; p = .047), property damage (OR: 1.29, 95% CI: 1.1–1.5, p = .002), and verbal aggression (OR: 1.35, 95% CI: 1.15–1.6, p controlling for adolescents’ sex, externalizing behaviors, and family income. When controlling for parents’ CPA, previous mother-to-adolescent aggression still predicted adolescents’ parent-directed physical aggression (OR: 5.56, 95% CI: 1.82–17.0, p = .003), and father-to-mother aggression predicted adolescents’ parent-directed verbal aggression (OR: 1.86, 95% CI: 1.0–3.3, p = .036). Emotion dysregulation and attitudes condoning aggression did not produce direct or moderated effects. Conclusions Adolescents’ parent-directed aggression deserves greater attention in discourse about lasting, adverse effects of even minor forms of parents’ physical aggression. Future research should investigate parent-directed aggression as an early

  20. Adolescents' aggression to parents: longitudinal links with parents' physical aggression.

    Science.gov (United States)

    Margolin, Gayla; Baucom, Brian R

    2014-11-01

    To investigate whether parents' previous physical aggression (PPA) exhibited during early adolescence is associated with adolescents' subsequent parent-directed aggression even beyond parents' concurrent physical aggression (CPA) and to investigate whether adolescents' emotion dysregulation and attitudes condoning child-to-parent aggression moderate associations. Adolescents (N = 93) and their parents participated in a prospective longitudinal study. Adolescents and parents reported at waves 1-3 on four types of parents' PPA (mother to adolescent, father to adolescent, mother to father, and father to mother). Wave 3 assessments also included adolescents' emotion dysregulation, attitudes condoning aggression, and externalizing behaviors. At waves 4 and 5, adolescents and parents reported on adolescents' parent-directed physical aggression, property damage, and verbal aggression and on parents' CPA. Parents' PPA emerged as a significant indicator of adolescents' parent-directed physical aggression (odds ratio [OR]: 1.25, 95% confidence interval [CI]: 1.0-1.55; p = .047), property damage (OR: 1.29, 95% CI: 1.1-1.5, p = .002), and verbal aggression (OR: 1.35, 95% CI: 1.15-1.6, p controlling for adolescents' sex, externalizing behaviors, and family income. When controlling for parents' CPA, previous mother-to-adolescent aggression still predicted adolescents' parent-directed physical aggression (OR: 5.56, 95% CI: 1.82-17.0, p = .003), and father-to-mother aggression predicted adolescents' parent-directed verbal aggression (OR: 1.86, 95% CI: 1.0-3.3, p = .036). Emotion dysregulation and attitudes condoning aggression did not produce direct or moderated the effects. Adolescents' parent-directed aggression deserves greater attention in discourse about lasting, adverse effects of even minor forms of parents' physical aggression. Future research should investigate parent-directed aggression as an early signal of aggression into adulthood. Copyright © 2014 Society for

  1. High SRPX2 protein expression predicts unfavorable clinical outcome in patients with prostate cancer

    Science.gov (United States)

    Zhang, Meng; Li, Xiaoli; Fan, Zhirui; Zhao, Jing; Liu, Shuzheng; Zhang, Mingzhi; Li, Huixiang; Goscinski, Mariusz Adam; Fan, Huijie; Suo, Zhenhe

    2018-01-01

    Background Sushi repeat-containing protein X-linked 2 (SRPX2) is overexpressed in a variety of different tumor tissues and correlated with poor prognosis in patients. Little research focuses on the role of SRPX2 expression in prostate cancer (PCa), and the clinicopathological significance of the protein expression in this tumor is relatively unknown. However, our previous transcriptome data from those cancer stem-like cells indicated the role of SRPX2 in PCa. Materials and methods In this study, RT-PCR and Western blotting were firstly used to examine the SRPX2 expression in three PCa cell lines including LNCaP, DU145, and PC3, and then SRPX2 protein expression was immunohistochemically investigated and statistically analyzed in a series of 106 paraffin-embedded PCa tissue specimens. Results Significantly lower levels of SRPX2 expression were verified in the LNCaP cells, compared with the expression in the aggressive DU145 and PC3 cells, in both mRNA and protein levels. Immunohistochemically, there were variable SRPX2 protein expressions in the clinical samples. Moreover, high levels of SRPX2 expression in the PCa tissues were significantly associated with Gleason score (P=0.008), lymph node metastasis (P=0.009), and distant metastasis (P=0.021). Furthermore, higher levels of SRPX2 expression in the PCa tissues were significantly associated with shorter overall survival (OS) (P<0.001). Conclusion Our results demonstrate that SRPX2 is highly expressed in aggressive PCa cells in vitro, and its protein expression in PCa is significantly associated with malignant clinical features and shorter OS, strongly indicating its prognostic value in prostate cancers. PMID:29881288

  2. The Relationship between Unstable Self-Esteem and Aggression: Differences in Reactive and Proactive Aggression

    Science.gov (United States)

    Lee, Eunju J.

    2014-01-01

    This study examines whether the instability of self-esteem (i.e., a high intraindividual variability in self-esteem) is differentially associated with different types of aggressive behavior by using a sample of 235 preadolescent children. Self-esteem was measured four times for four consecutive days, and proactive and reactive aggressive behaviors…

  3. High school students in a health career promotion program report fewer acts of aggression and violence.

    Science.gov (United States)

    Oscós-Sánchez, Manuel Ángel; Lesser, Janna; Oscós-Flores, L Dolores

    2013-01-01

    This study examined the effects of two school-based programs on the perpetration of nonphysical aggression, physical violence, and intimate partner violence among high-risk secondary school students in an economically disadvantaged and predominantly Latino school district. The intervention program was El Joven Noble, and the control program was the Teen Medical Academy. The study used a repeated-measures quasi-experimental intervention/control design. The participants self-reported the previous 30 days' acts of nonphysical aggression, physical violence, and intimate partner violence at baseline and at 3 and 9 months after enrollment. Program- and grade-level effects at 3 and 9 months were examined using three-factor analyses of covariance models with one factor for repeated measures. The covariate in each of the models was the baseline measure of the dependent outcomes. No significant baseline differences were found between the participants in the intervention (n = 96) and control (n = 127) programs. At 9 months after enrollment in the study, high school students who participated in the Teen Medical Academy reported fewer acts of nonphysical aggression (p violence (p = .002) than high school students who participated in El Joven Noble. Students who participated in the Teen Medical Academy also reported fewer acts of intimate partner violence (p = .02) than students who participated in El Joven Noble. High school students who participated in a health career promotion program reported fewer acts of aggression and violence as compared with high school students who participated in a culturally tailored character development program. Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  4. Callous-unemotional traits, proactive aggression, and treatment outcomes of aggressive children with attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Blader, Joseph C; Pliszka, Steven R; Kafantaris, Vivian; Foley, Carmel A; Crowell, Judith A; Carlson, Gabrielle A; Sauder, Colin L; Margulies, David M; Sinha, Christa; Sverd, Jeffrey; Matthews, Thomas L; Bailey, Brigitte Y; Daviss, W Burleson

    2013-12-01

    Stimulant treatment improves impulse control among children with attention-deficit/hyperactivity disorder (ADHD). Decreased aggression often accompanies stimulant pharmacotherapy, suggesting that impulsiveness is integral to aggressive behavior in these children. However, children with high callous-unemotional (CU) traits and proactive aggression may benefit less from ADHD pharmacotherapy, because their aggressive behavior seems more purposeful and deliberate. This study's objective was to determine whether pretreatment CU traits and proactive aggression affect treatment outcomes among aggressive children with ADHD receiving stimulant monotherapy. We implemented a stimulant optimization protocol with 160 children 6 to 13 years of age (mean [SD] age of 9.31 [2.02] years; 78.75% male) with ADHD, oppositional defiant or conduct disorder, and significant aggressive behavior. Family-focused behavioral intervention was provided concurrently. The primary outcome was the Retrospective Modified Overt Aggression Scale. The Antisocial Process Screening Device and the Aggression Scale, also completed by parents, measured CU traits and proactive aggression, respectively. Analyses examined moderating effects of CU traits and proactive aggression on outcomes. In all, 82 children (51%) experienced remission of aggressive behavior. Neither CU traits nor proactive aggression predicted remission (CU traits: odds ratio [OR] = 0.94, 95% CI = 0.80-1.11; proactive aggression, OR = 1.05, 95% CI = 0.86-1.29). Children whose overall aggression remitted showed decreases in CU traits (effect size = -0.379, 95% CI = -0.60 to -0.16) and proactive aggression (effect size = -0.463, 95% CI = -0.69 to -0.23). Findings suggest that pretreatment CU traits and proactive aggression do not forecast worse outcomes for aggressive children with ADHD receiving optimized stimulant pharmacotherapy. With such treatment, CU traits and proactive aggression may decline alongside other behavioral improvements

  5. PKCα expression is a marker for breast cancer aggressiveness

    Directory of Open Access Journals (Sweden)

    Jirström Karin

    2010-04-01

    Full Text Available Abstract Background Protein kinase C (PKC isoforms are potential targets for breast cancer therapy. This study was designed to evaluate which PKC isoforms might be optimal targets for different breast cancer subtypes. Results In two cohorts of primary breast cancers, PKCα levels correlated to estrogen and progesterone receptor negativity, tumor grade, and proliferative activity, whereas PKCδ and PKCε did not correlate to clinicopathological parameters. Patients with PKCα-positive tumors showed poorer survival than patients with PKCα-negative tumors independently of other factors. Cell line studies demonstrated that PKCα levels are high in MDA-MB-231 and absent in T47D cells which proliferated slower than other cell lines. Furthermore, PKCα silencing reduced proliferation of MDA-MB-231 cells. PKCα inhibition or downregulation also reduced cell migration in vitro. Conclusions PKCα is a marker for poor prognosis of breast cancer and correlates to and is important for cell functions associated with breast cancer progression.

  6. Aggression and coexistence in female caribou

    Science.gov (United States)

    Weckerly, Floyd W.; Ricca, Mark A.

    2014-01-01

    Female caribou (Rangifer tarandus) are highly gregarious, yet there has been little study of the behavioral mechanisms that foster coexistence. Quantifying patterns of aggression between male and female, particularly in the only cervid taxa where both sexes grow antlers, should provide insight into these mechanisms. We asked if patterns of aggression by male and female caribou followed the pattern typically noted in other polygynous cervids, in which males display higher frequencies and intensity of aggression. From June to August in 2011 and 2012, we measured the frequency and intensity of aggression across a range of group sizes through focal animal sampling of 170 caribou (64 males and 106 females) on Adak Island in the Aleutian Archipelago, Alaska. Males in same-sex and mixed-sex groups and females in mixed-sex groups had higher frequencies of aggression than females in same-sex groups. Group size did not influence frequency of aggression. Males displayed more intense aggression than females. Frequent aggression in mixed-sex groups probably reflects lower tolerance of males for animals in close proximity. Female caribou were less aggressive and more gregarious than males, as in other polygynous cervid species.

  7. Effect of high-dose intravenous vitamin C on inflammation in cancer patients

    Directory of Open Access Journals (Sweden)

    Mikirova Nina

    2012-09-01

    Full Text Available Abstract Background An inflammatory component is present in the microenvironment of most neoplastic tissues. Inflammation and elevated C-reactive protein (CRP are associated with poor prognosis and decreased survival in many types of cancer. Vitamin C has been suggested as having both a preventative and therapeutic role in a number of pathologies when administered at much higher-than-recommended dietary allowance levels. Since in vitro studies demonstrated inhibition of pro-inflammatory pathways by millimolar concentrations of vitamin C, we decided to analyze the effects of high dose IVC therapy in suppression of inflammation in cancer patients. Methods 45 patients with prostate cancer, breast cancer, bladder cancer, pancreatic cancer, lung cancer, thyroid cancer, skin cancer and B-cell lymphoma were treated at the Riordan Clinic by high doses of vitamin C (7.5 g -50 g after standard treatments by conventional methods. CRP and tumor markers were measured in serum or heparin-plasma as a routine analysis. In addition, serum samples were collected before and after the IVCs for the cytokine kit tests. Results According to our data positive response to treatment, which was demonstrated by measurements of C- reactive protein, was found in 75% of patients and progression of the inflammation in 25% of patients. IVC treatments on all aggressive stage cancer patients showed the poor response of treatment. There was correlation between tumor markers (PSA, CEA, CA27.29 and CA15-3 and changes in the levels of C-reactive protein. Our test of the effect of IVC on pro-inflammatory cytokines demonstrated that inflammation cytokines IL-1α, IL-2, IL-8, TNF-α, chemokine eotaxin and CRP were reduced significantly after treatments. Conclusions The high dose intravenous ascorbic acid therapy affects C-reactive protein levels and pro-inflammation cytokines in cancer patients. In our study, we found that modulation of inflammation by IVC correlated with decreases

  8. Combat high or traumatic stress: violent offending is associated with appetitive aggression but not with symptoms of traumatic stress

    Directory of Open Access Journals (Sweden)

    Anke eKöbach

    2015-01-01

    Full Text Available Former members of armed groups in eastern DRCongo had typically witnessed, experienced and perpetrated extreme forms of violence. Enhanced trauma-related symptoms had been shown in prior research. But also lashing out in self-defense is a familiar response to threat defined as reactive aggression. Another potential response is appetitive aggression, in which the perpetration of excessive violence is perceived as pleasurable (combat high. What roles do these forms of aggressive behavior play in modern warfare and how are they related to posttraumatic stress symptoms? To answer the question, we sought to determine predictors for appetitive aggressive and trauma-related mental illness, and investigated the frequency of psychopathological symptoms for high- and low-intensity conflict demobilization settings. To this end, we interviewed 213 former members of (paramilitary groups in the eastern Democratic Republic of Congo in regard to their combat exposure, posttraumatic stress, appetitive aggression, depression, suicidality, and drug dependence. Random forest regression embedded in a conditional inference framework revealed that perpetrated violent acts are not necessarily stressful. In fact, the experience of violent acts that typically implicated salient cues of hunting (e.g., blood, suffering of the victim, etc. had the strongest association with an appetite for aggression. Furthermore, the number of lifetime perpetrated violent acts was the most important predictor of appetitive aggression. However, the number of perpetrated violent acts did not significantly affect the posttraumatic stress. Greater intensity of conflict was associated with more severe posttraumatic stress symptoms and depression. Psychotherapeutic interventions that address appetitive aggression in addition to trauma-related mental illness, including drug dependence, therefore seem indispensible for a successful reintegration of those who fought in the current civil wars.

  9. Violent and nonviolent video games differentially affect physical aggression for individuals high vs. low in dispositional anger.

    Science.gov (United States)

    Engelhardt, Christopher R; Bartholow, Bruce D; Saults, J Scott

    2011-01-01

    Although numerous experiments have shown that exposure to violent video games (VVG) causes increases in aggression, relatively few studies have investigated the extent to which this effect differs as a function of theoretically relevant individual difference factors. This study investigated whether video game content differentially influences aggression as a function of individual differences in trait anger. Participants were randomly assigned to play a violent or nonviolent video game before completing a task in which they could behave aggressively. Results showed that participants high in trait anger were the most aggressive, but only if they first played a VVG. This relationship held while statistically controlling for dimensions other than violent content on which game conditions differed (e.g. frustration, arousal). Implications of these findings for models explaining the effects of video games on behavior are discussed. © 2011 Wiley Periodicals, Inc.

  10. High Loading of Polygenic Risk for ADHD in Children With Comorbid Aggression

    Science.gov (United States)

    Hamshere, Marian L.; Langley, Kate; Martin, Joanna; Agha, Sharifah Shameem; Stergiakouli, Evangelia; Anney, Richard J.L.; Buitelaar, Jan; Faraone, Stephen V.; Lesch, Klaus-Peter; Neale, Benjamin M.; Franke, Barbara; Sonuga-Barke, Edmund; Asherson, Philip; Merwood, Andrew; Kuntsi, Jonna; Medland, Sarah E.; Ripke, Stephan; Steinhausen, Hans-Christoph; Freitag, Christine; Reif, Andreas; Renner, Tobias J.; Romanos, Marcel; Romanos, Jasmin; Warnke, Andreas; Meyer, Jobst; Palmason, Haukur; Vasquez, Alejandro Arias; Lambregts-Rommelse, Nanda; Roeyers, Herbert; Biederman, Joseph; Doyle, Alysa E.; Hakonarson, Hakon; Rothenberger, Aribert; Banaschewski, Tobias; Oades, Robert D.; McGough, James J.; Kent, Lindsey; Williams, Nigel; Owen, Michael J.; Holmans, Peter

    2013-01-01

    Objective Although attention deficit hyperactivity disorder (ADHD) is highly heritable, genome-wide association studies (GWAS) have not yet identified any common genetic variants that contribute to risk. There is evidence that aggression or conduct disorder in children with ADHD indexes higher genetic loading and clinical severity. The authors examine whether common genetic variants considered en masse as polygenic scores for ADHD are especially enriched in children with comorbid conduct disorder. Method Polygenic scores derived from an ADHD GWAS meta-analysis were calculated in an independent ADHD sample (452 case subjects, 5,081 comparison subjects). Multivariate logistic regression analyses were employed to compare polygenic scores in the ADHD and comparison groups and test for higher scores in ADHD case subjects with comorbid conduct disorder relative to comparison subjects and relative to those without comorbid conduct disorder. Association with symptom scores was tested using linear regression. Results Polygenic risk for ADHD, derived from the meta-analysis, was higher in the independent ADHD group than in the comparison group. Polygenic score was significantly higher in ADHD case subjects with conduct disorder relative to ADHD case subjects without conduct disorder. ADHD polygenic score showed significant association with comorbid conduct disorder symptoms. This relationship was explained by the aggression items. Conclusions Common genetic variation is relevant to ADHD, especially in individuals with comorbid aggression. The findings suggest that the previously published ADHD GWAS meta-analysis contains weak but true associations with common variants, support for which falls below genome-wide significance levels. The findings also highlight the fact that aggression in ADHD indexes genetic as well as clinical severity. PMID:23599091

  11. From provocation to aggression: the neural network

    OpenAIRE

    Repple, J.; Pawliczek, C.M.; Voss, B.; Siegel, S.; Schneider, F.; Kohn, N.; Habel, U.

    2017-01-01

    Background In-vivo observations of neural processes during human aggressive behavior are difficult to obtain, limiting the number of studies in this area. To address this gap, the present study implemented a social reactive aggression paradigm in 29 healthy men, employing non-violent provocation in a two-player game to elicit aggressive behavior in fMRI settings. Results Participants responded more aggressively after high provocation reflected in taking more money from their opponents. Compar...

  12. Aerobic Glycolysis as a Marker of Tumor Aggressiveness: Preliminary Data in High Grade Human Brain Tumors

    Directory of Open Access Journals (Sweden)

    Andrei G. Vlassenko

    2015-01-01

    Full Text Available Objectives. Glucose metabolism outside of oxidative phosphorylation, or aerobic glycolysis (AG, is a hallmark of active cancer cells that is not directly measured with standard 18F-fluorodeoxyglucose (FDG positron emission tomography (PET. In this study, we characterized tumor regions with elevated AG defined based on PET measurements of glucose and oxygen metabolism. Methods. Fourteen individuals with high-grade brain tumors underwent structural MR scans and PET measurements of cerebral blood flow (CBF, oxygen (CMRO2 and glucose (CMRGlu metabolism, and AG, using 15O-labeled CO, O2 and H2O, and FDG, and were compared to a normative cohort of 20 age-matched individuals. Results. Elevated AG was observed in most high-grade brain tumors and it was associated with decreased CMRO2 and CBF, but not with significant changes in CMRGlu. Elevated AG was a dramatic and early sign of tumor growth associated with decreased survival. AG changes associated with tumor growth were differentiated from the effects of nonneoplastic processes such as epileptic seizures. Conclusions. Our findings demonstrate that high-grade brain tumors exhibit elevated AG as a marker of tumor growth and aggressiveness. AG may detect areas of active tumor growth that are not evident on conventional FDG PET.

  13. Socialization of Physical and Social Aggression in Early Adolescents' Peer Groups: High-Status Peers, Individual Status, and Gender

    Science.gov (United States)

    Shi, Bing; Xie, Hongling

    2012-01-01

    The influence of high-status peers on a target individual's physical and manipulative social aggression in peer groups was examined in a diverse sample of seventh-grade students. A total of 245 individual members belonging to 65 groups were included in analyses. Aggression was assessed by peer and victim nominations in the fall and spring…

  14. Inhibition of tumor vasculogenic mimicry and prolongation of host survival in highly aggressive gallbladder cancers by norcantharidin via blocking the ephrin type a receptor 2/focal adhesion kinase/paxillin signaling pathway.

    Directory of Open Access Journals (Sweden)

    Hui Wang

    Full Text Available Vasculogenic mimicry (VM is a newly-defined tumor microcirculation pattern in highly aggressive malignant tumors. We recently reported tumor growth and VM formation of gallbladder cancers through the contribution of the ephrin type a receptor 2 (EphA2/focal adhesion kinase (FAK/Paxillin signaling pathways. In this study, we further investigated the anti-VM activity of norcantharidin (NCTD as a VM inhibitor for gallbladder cancers and the underlying mechanisms. In vivo and in vitro experiments to determine the effects of NCTD on tumor growth, host survival, VM formation of GBC-SD nude mouse xenografts, and vasculogenic-like networks, malignant phenotypes i.e., proliferation, apoptosis, invasion and migration of GBC-SD cells. Expression of VM signaling-related markers EphA2, FAK and Paxillin in vivo and in vitro were examined by immunofluorescence, western blotting and real-time polymerase chain reaction (RT-PCR, respectively. The results showed that after treatment with NCTD, GBC-SD cells were unable to form VM structures when injecting into nude mouse, growth of the xenograft was inhibited and these observations were confirmed by facts that VM formation by three-dimensional (3-D matrix, proliferation, apoptosis, invasion, migration of GBC-SD cells were affected; and survival time of the xenograft mice was prolonged. Furthermore, expression of EphA2, FAK and Paxillin proteins/mRNAs of the xenografts was downregulated. Thus, we concluded that NCTD has potential anti-VM activity against human gallbladder cancers; one of the underlying mechanisms may be via blocking the EphA2/FAK/Paxillin signaling pathway.

  15. Subjective aggression during alcohol and cannabis intoxication before and after aggression exposure.

    Science.gov (United States)

    De Sousa Fernandes Perna, E B; Theunissen, E L; Kuypers, K P C; Toennes, S W; Ramaekers, J G

    2016-09-01

    Alcohol and cannabis use have been implicated in aggression. Alcohol consumption is known to facilitate aggression, whereas a causal link between cannabis and aggression has not been clearly demonstrated. This study investigated the acute effects of alcohol and cannabis on subjective aggression in alcohol and cannabis users, respectively, following aggression exposure. Drug-free controls served as a reference. It was hypothesized that aggression exposure would increase subjective aggression in alcohol users during alcohol intoxication, whereas it was expected to decrease subjective aggression in cannabis users during cannabis intoxication. Heavy alcohol (n = 20) and regular cannabis users (n = 21), and controls (n = 20) were included in a mixed factorial study. Alcohol and cannabis users received single doses of alcohol and placebo or cannabis and placebo, respectively. Subjective aggression was assessed before and after aggression exposure consisting of administrations of the point-subtraction aggression paradigm (PSAP) and the single category implicit association test (SC-IAT). Testosterone and cortisol levels in response to alcohol/cannabis treatment and aggression exposure were recorded as secondary outcome measures. Subjective aggression significantly increased following aggression exposure in all groups while being sober. Alcohol intoxication increased subjective aggression whereas cannabis decreased the subjective aggression following aggression exposure. Aggressive responses during the PSAP increased following alcohol and decreased following cannabis relative to placebo. Changes in aggressive feeling or response were not correlated to the neuroendocrine response to treatments. It is concluded that alcohol facilitates feelings of aggression whereas cannabis diminishes aggressive feelings in heavy alcohol and regular cannabis users, respectively.

  16. Elevated mammaglobin (h-MAM) expression in breast cancer is associated with clinical and biological features defining a less aggressive tumour phenotype

    International Nuclear Information System (INIS)

    Núñez-Villar, MJ; Martínez-Arribas, F; Pollán, M; Lucas, AR; Sánchez, J; Tejerina, A; Schneider, J

    2003-01-01

    Mammaglobin (h-MAM) is expressed mainly by breast epithelial cells, and this feature has been used to detect circulating breast cancer cells and occult metastases in sentinel axillary lymph nodes of breast cancer patients. However, the biological role of mammaglobin is completely unknown. We studied 128 fresh-frozen breast cancer specimens by means of reverse transcriptase–polymerase chain reaction and quantified their h-MAM mRNA expression. This was then correlated with histological and nuclear grade, oestrogen and progesterone receptor expression, c-erb-B2 and mutant p53 expression, as well as with cellular proliferation measured by means of the Ki67 labelling index, DNA ploidy and S-phase, and finally with the presence or not of invaded axillary nodes in the mastectomy specimen. In the univariate analysis, high h-MAM expression (above the median for the whole group) correlated significantly (P < 0.05) with oestrogen and progesterone receptor expression, diploid DNA content, low Ki67 labelling index, low nuclear grade and almost significantly (P = 0.058) with the absence of axillary nodal invasion in the mastectomy specimen. In a final, multivariate model, only progesterone receptor expression, diploid DNA content and absence of nodal invasion were found to be independently associated with high h-MAM expression. All of the features associated with mammaglobin expression reflect, without exception, a less aggressive tumour phenotype. Further studies are needed to clarify whether this is attributable to h-MAM expression itself, or to another mechanism of which mammaglobin expression forms part

  17. Toward a better understanding of the comparatively high prostate cancer incidence rates in Utah.

    Science.gov (United States)

    Merrill, Ray M; Hilton, Sterling C; Wiggins, Charles L; Sturgeon, Jared D

    2003-04-29

    This study assesses whether comparatively high prostate cancer incidence rates among white men in Utah represent higher rates among members of the Church of Jesus Christ of Latter-day Saints (LDS or Mormons), who comprise about 70% of the state's male population, and considers the potential influence screening has on these rates. Analyses are based on 14,693 histologically confirmed invasive prostate cancer cases among men aged 50 years and older identified through the Utah Cancer Registry between 1985 and 1999. Cancer records were linked to LDS Church membership records to determine LDS status. Poisson regression was used to derive rate ratios of LDS to nonLDS prostate cancer incidence, adjusted for age, disease stage, calendar time, and incidental detection. LDS men had a 31% (95% confidence interval, 26%-36%) higher incidence rate of prostate cancer than nonLDS men during the study period. Rates were consistently higher among LDS men over time (118% in 1985-88, 20% in 1989-92, 15% in 1993-1996, and 13% in 1997-99); age (13% in ages 50-59, 48% in ages 60-69, 28% in ages 70-79, and 16% in ages 80 and older); and stage (36% in local/regional and 17% in unstaged). An age- and stage-shift was observed for both LDS and nonLDS men, although more pronounced among LDS men. Comparatively high prostate cancer incidence rates among LDS men in Utah are explained, at least in part, by more aggressive screening among these men.

  18. Can Both Low and High Self-Esteem Be Related to Aggression in Children?

    Science.gov (United States)

    Diamantopoulou, Sofia; Rydell, Ann-Margret; Henricsson, Lisbeth

    2008-01-01

    This study examined the opposing hypotheses that either low or exaggerated but disputed self-esteem is related to aggression in 652 12-year-old schoolchildren. Children provided peer nominations of social acceptance and of physical aggression, self-ratings of global self-worth and of social satisfaction. Teachers rated aggressive behavior and…

  19. Profiling plasma extracellular vesicle by pluronic block-copolymer based enrichment method unveils features associated with breast cancer aggression, metastasis and invasion.

    Science.gov (United States)

    Zhong, Zhenyu; Rosenow, Matthew; Xiao, Nick; Spetzler, David

    2018-01-01

    Extracellular vesicle (EV)-based liquid biopsies have been proposed to be a readily obtainable biological substrate recently for both profiling and diagnostics purposes. Development of a fast and reliable preparation protocol to enrich such small particles could accelerate the discovery of informative, disease-related biomarkers. Though multiple EV enrichment protocols are available, in terms of efficiency, reproducibility and simplicity, precipitation-based methods are most amenable to studies with large numbers of subjects. However, the selectivity of the precipitation becomes critical. Here, we present a simple plasma EV enrichment protocol based on pluronic block copolymer. The enriched plasma EV was able to be verified by multiple platforms. Our results showed that the particles enriched from plasma by the copolymer were EV size vesicles with membrane structure; proteomic profiling showed that EV-related proteins were significantly enriched, while high-abundant plasma proteins were significantly reduced in comparison to other precipitation-based enrichment methods. Next-generation sequencing confirmed the existence of various RNA species that have been observed in EVs from previous studies. Small RNA sequencing showed enriched species compared to the corresponding plasma. Moreover, plasma EVs enriched from 20 advanced breast cancer patients and 20 age-matched non-cancer controls were profiled by semi-quantitative mass spectrometry. Protein features were further screened by EV proteomic profiles generated from four breast cancer cell lines, and then selected in cross-validation models. A total of 60 protein features that highly contributed in model prediction were identified. Interestingly, a large portion of these features were associated with breast cancer aggression, metastasis as well as invasion, consistent with the advanced clinical stage of the patients. In summary, we have developed a plasma EV enrichment method with improved precipitation selectivity

  20. Surgical strategies in patients with gallbladder cancer: nihilism to optimism.

    Science.gov (United States)

    Sikora, Sadiq S; Singh, Rajneesh K

    2006-06-15

    Gallbladder cancer is an aggressive disease with dismal results of surgical treatment and a poor prognosis. However, over the last few decades selected groups have reported improved results with aggressive surgery for gallbladder cancer. Review of recent world literature was done to provide an update on the current concepts of surgical treatment of this disease. Long-term survival is possible in early stage gallbladder carcinoma. Tis and T1a gallbladder carcinoma can be treated with simple cholecystectomy only. However, in T1b and beyond cancers, aggressive surgery (extended cholecystectomy) is important in improving the long-term prognosis. Laparoscopic cholecystectomy should not be performed where there is a high index of suspicion of malignancy due to the frequent association with factors (such as gallbladder perforation and bile spill) which may lead to implantation of cancer cells and dissemination. Surgical resection for advanced carcinoma gallbladder is recommended only if a potentially curative R0 resection is possible. Aggressive surgery with vascular and multivisceral resection has been shown to be feasible albeit with an increase in mortality and morbidity. However, the true benefit of these radical resections is yet to be realized, as the actual number of long-term survivors of advanced gallbladder carcinoma is few. Surgery for gallbladder carcinoma, like other malignancies, has the potential to be curative only in local or regional disease. Pattern of loco-regional spread of disease dictates the surgical procedure. Radical surgery improves survival in early gallbladder carcinoma. The long-term benefit of aggressive surgery for advanced disease is unclear and may be offset by the high mortality and morbidity. Copyright 2006 Wiley-Liss, Inc.

  1. The influence of obesity in patients with prostate cancer - Review of the literature

    Directory of Open Access Journals (Sweden)

    Maximilien C. Goris Gbenou

    2013-04-01

    Full Text Available ABSTRACTRecent studies have demonstrated an association between higher body mass index and increased aggressiveness in prostate cancer.The present narrative review, based on a search of Medline® and Embase® databases from October 1982 to October 2012, explores the relationship between higher body mass index and localized prostate cancer. In particular, the current epidemiological and mechanistic evidence for interactions between obesity and prostate cancer are discussed.Obesity is associated with alterations in androgen levels, decreased sex hormone binding globulin and increased estrogen levels, insulin resistance, hyperglycemia, alterations in plasma lipoprotein levels particularly raised triglycerides and reduced high density lipoprotein, decreased levels of adiponectin, and increased levels of circulating insulin-growth factor- 1, leptin and dietary saturated fats. Obese men have more aggressive prostate cancer with a greater percentage prostate involvement, increased tumor volume and higher-grade disease, enlarged prostates, high prostate-specific antigen levels, increased risk of having positive margins and recurrence.Moreover, there is strong evidence of the beneficial effects of functional foods for the treatment of obesity. Additionally, an increasing number of studies support that obesity-induced inflammation plays an important role in the development of obesity-related pathologies. Despite, the beneficial role of nutriment in prostate cancer control, the use of functional foods in prostate cancer is not recommended for lack of large epidemiological studies.This data supports the hypothesis that obese men have more aggressive prostate cancers and that the obesity is a modifiable risk factor of prostate cancer.Key Words: prostate cancer, metabolic syndrome, obesity, high BMI, risk factor, diet, functional foods.

  2. Signaling aggression.

    Science.gov (United States)

    van Staaden, Moira J; Searcy, William A; Hanlon, Roger T

    2011-01-01

    From psychological and sociological standpoints, aggression is regarded as intentional behavior aimed at inflicting pain and manifested by hostility and attacking behaviors. In contrast, biologists define aggression as behavior associated with attack or escalation toward attack, omitting any stipulation about intentions and goals. Certain animal signals are strongly associated with escalation toward attack and have the same function as physical attack in intimidating opponents and winning contests, and ethologists therefore consider them an integral part of aggressive behavior. Aggressive signals have been molded by evolution to make them ever more effective in mediating interactions between the contestants. Early theoretical analyses of aggressive signaling suggested that signals could never be honest about fighting ability or aggressive intentions because weak individuals would exaggerate such signals whenever they were effective in influencing the behavior of opponents. More recent game theory models, however, demonstrate that given the right costs and constraints, aggressive signals are both reliable about strength and intentions and effective in influencing contest outcomes. Here, we review the role of signaling in lieu of physical violence, considering threat displays from an ethological perspective as an adaptive outcome of evolutionary selection pressures. Fighting prowess is conveyed by performance signals whose production is constrained by physical ability and thus limited to just some individuals, whereas aggressive intent is encoded in strategic signals that all signalers are able to produce. We illustrate recent advances in the study of aggressive signaling with case studies of charismatic taxa that employ a range of sensory modalities, viz. visual and chemical signaling in cephalopod behavior, and indicators of aggressive intent in the territorial calls of songbirds. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Epidemiology of cancer-related venous thromboembolism

    OpenAIRE

    Wun, Ted; White, Richard H.

    2009-01-01

    Recent studies have better defined the epidemiology of venous thromboembolism (VTE) in cancer patients. The incidence is highest in patients who have metastatic disease at the time of presentation and who have fast growing, biologically aggressive cancers associated with a poor prognosis. The incidence is also high in patients with haematological cancers. Other specific risk factors that affect the incidence of VTE include undergoing invasive neurosurgery, the number of underlying chronic co-...

  4. High fat, low carbohydrate diet limit fear and aggression in Göttingen minipigs.

    Directory of Open Access Journals (Sweden)

    Annika Maria Juul Haagensen

    Full Text Available High fat, low carbohydrate diets have become popular, as short-term studies show that such diets are effective for reducing body weight, and lowering the risk of diabetes and cardiovascular disease. There is growing evidence from both humans and other animals that diet affects behaviour and intake of fat has been linked, positively and negatively, with traits such as exploration, social interaction, anxiety and fear. Animal models with high translational value can help provide relevant and important information in elucidating potential effects of high fat, low carbohydrate diets on human behaviour. Twenty four young, male Göttingen minipigs were fed either a high fat/cholesterol, low carbohydrate diet or a low fat, high carbohydrate/sucrose diet in contrast to a standard low fat, high carbohydrate minipig diet. Spontaneous behaviour was observed through video recordings of home pens and test-related behaviours were recorded during tests involving animal-human contact and reaction towards a novel object. We showed that the minipigs fed a high fat/cholesterol, low carbohydrate diet were less aggressive, showed more non-agonistic social contact and had fewer and less severe skin lesions and were less fearful of a novel object than minipigs fed low fat, high carbohydrate diets. These results found in a porcine model could have important implications for general health and wellbeing of humans and show the potential for using dietary manipulations to reduce aggression in human society.

  5. Aggression By Whom–Aggression Toward Whom: Behavioral Predictors of Same- and Other-Gender Aggression in Early Childhood

    Science.gov (United States)

    Hanish, Laura D.; Sallquist, Julie; DiDonato, Matthew; Fabes, Richard A.; Martin, Carol Lynn

    2012-01-01

    This study assessed girls’ and boys’ dominance-related behaviors (aggressive, commanding, submissive, and neutral behaviors) as they naturally occurred during interactions with male and female peers and evaluated the possibility that such behaviors elicit aggression from peers. Using a focal observational procedure, young girls’ and boys’ (N = 170; 54% boys) naturally occurring dominance-related behaviors and male and female peers’ aggressive responses to those behaviors were recorded multiple times each week across the academic year. Findings suggested that same-gender aggression occurred at similar rates as other-gender aggression once tendencies toward gender segregated play were controlled. Additionally, there were both gender-based similarities and differences in children’s use of dominance-related behaviors in peer interactions and as antecedents for peers’ aggression. The findings have implications for the literatures on aggression and gendered peer interactions. PMID:22369337

  6. Boswellia sacra essential oil induces tumor cell-specific apoptosis and suppresses tumor aggressiveness in cultured human breast cancer cells

    Science.gov (United States)

    2011-01-01

    Background Gum resins obtained from trees of the Burseraceae family (Boswellia sp.) are important ingredients in incense and perfumes. Extracts prepared from Boswellia sp. gum resins have been shown to possess anti-inflammatory and anti-neoplastic effects. Essential oil prepared by distillation of the gum resin traditionally used for aromatic therapy has also been shown to have tumor cell-specific anti-proliferative and pro-apoptotic activities. The objective of this study was to optimize conditions for preparing Boswellea sacra essential oil with the highest biological activity in inducing tumor cell-specific cytotoxicity and suppressing aggressive tumor phenotypes in human breast cancer cells. Methods Boswellia sacra essential oil was prepared from Omani Hougari grade resins through hydrodistillation at 78 or 100 oC for 12 hours. Chemical compositions were identified by gas chromatography-mass spectrometry; and total boswellic acids contents were quantified by high-performance liquid chromatography. Boswellia sacra essential oil-mediated cell viability and death were studied in established human breast cancer cell lines (T47D, MCF7, MDA-MB-231) and an immortalized normal human breast cell line (MCF10-2A). Apoptosis was assayed by genomic DNA fragmentation. Anti-invasive and anti-multicellular tumor properties were evaluated by cellular network and spheroid formation models, respectively. Western blot analysis was performed to study Boswellia sacra essential oil-regulated proteins involved in apoptosis, signaling pathways, and cell cycle regulation. Results More abundant high molecular weight compounds, including boswellic acids, were present in Boswellia sacra essential oil prepared at 100 oC hydrodistillation. All three human breast cancer cell lines were sensitive to essential oil treatment with reduced cell viability and elevated cell death, whereas the immortalized normal human breast cell line was more resistant to essential oil treatment. Boswellia sacra

  7. Normative beliefs about aggression and cyber aggression among young adults: a longitudinal investigation.

    Science.gov (United States)

    Wright, Michelle F; Li, Yan

    2013-01-01

    This longitudinal study examined normative beliefs about aggression (e.g., face-to-face, cyber) in relation to the engagement in cyber aggression 6 months later among 126 (69 women) young adults. Participants completed electronically administered measures assessing their normative beliefs, face-to-face and cyber aggression at Time 1, and cyber aggression 6 months later (Time 2). We found that men reported more cyber relational and verbal aggression when compared to women. After controlling for each other, Time 1 face-to-face relational aggression was positively related to Time 2 cyber relational aggression, whereas Time 1 face-to-face verbal aggression was positively related to Time 2 cyber verbal aggression. Normative beliefs regarding cyber aggression was positively related to both forms of cyber aggression 6 months later, after controlling for normative beliefs about face-to-face aggression. Furthermore, a significant two-way interaction between Time 1 cyber relational aggression and normative beliefs about cyber relational aggression was found. Follow-up analysis showed that Time 1 cyber relational aggression was more strongly related to Time 2 cyber relational aggression when young adults held higher normative beliefs about cyber relational aggression. A similar two-way interaction was found for cyber verbal aggression such that the association between Time 1 and Time 2 cyber verbal aggression was stronger at higher levels of normative beliefs about cyber verbal aggression. Results are discussed in terms of the social cognitive and behavioral mechanisms associated with the engagement of cyber aggression. © 2013 Wiley Periodicals, Inc.

  8. Breast MR imaging in women at high-risk of breast cancer. Is something changing in early breast cancer detection?

    International Nuclear Information System (INIS)

    Sardanelli, Francesco; Podo, Franca

    2007-01-01

    In the last few years, several papers have addressed the introduction of contrast-enhanced MR imaging for screening women at high risk for breast cancer. Taking in consideration five prospective studies, on 3,571 screened women with hereditary predisposition to the disease and 9,652 rounds, we found that 168 patients were diagnosed with breast cancer (155 screen-detected, eight interval, and five cancers excluded from analysis) with a detection rate per year of 1.7%. These cancers were small (49% equal to or less than 10 mm in diameter) but aggressive, 82% being invasive and 49% with histologic grade 3; however, only 19% of these invasive cancers were associated with nodal involvement. The pooled sensitivity was 16% for clinical breast examination, 40% for mammography, 43% for ultrasound, and 81% for MR. The positive predictive value (calculated on the basis of the number of invasive diagnostic procedures due to false positives) was 33%, 47%, 18%, and 53%, respectively. Aim of the present article is to present the historical development of MR imaging of breast tumors that made this application theoretically and technically possible, to explain what strategic problems we face in the presence of a hereditary predisposition to the disease, to review the main results of the published studies, and to outline open problems and future perspectives. (orig.)

  9. The Role of MRI in Prostate Cancer Active Surveillance

    Directory of Open Access Journals (Sweden)

    Linda M. Johnson

    2014-01-01

    Full Text Available Prostate cancer is the most common cancer diagnosis in American men, excluding skin cancer. The clinical behavior of prostate cancer varies from low-grade, slow growing tumors to high-grade aggressive tumors that may ultimately progress to metastases and cause death. Given the high incidence of men diagnosed with prostate cancer, conservative treatment strategies such as active surveillance are critical in the management of prostate cancer to reduce therapeutic complications of radiation therapy or radical prostatectomy. In this review, we will review the role of multiparametric MRI in the selection and follow-up of patients on active surveillance.

  10. In Vitro and In Vivo Activity of IMGN853, an Antibody-Drug Conjugate Targeting Folate Receptor Alpha Linked to DM4, in Biologically Aggressive Endometrial Cancers.

    Science.gov (United States)

    Altwerger, Gary; Bonazzoli, Elena; Bellone, Stefania; Egawa-Takata, Tomomi; Menderes, Gulden; Pettinella, Francesca; Bianchi, Anna; Riccio, Francesco; Feinberg, Jacqueline; Zammataro, Luca; Han, Chanhee; Yadav, Ghanshyam; Dugan, Katherine; Morneault, Ashley; Ponte, Jose F; Buza, Natalia; Hui, Pei; Wong, Serena; Litkouhi, Babak; Ratner, Elena; Silasi, Dan-Arin; Huang, Gloria S; Azodi, Masoud; Schwartz, Peter E; Santin, Alessandro D

    2018-05-01

    Grade 3 endometrioid and uterine serous carcinomas (USC) account for the vast majority of endometrial cancer deaths. The purpose of this study was to determine folic acid receptor alpha (FRα) expression in these biologically aggressive (type II) endometrial cancers and evaluate FRα as a targetable receptor for IMGN853 (mirvetuximab soravtansine). The expression of FRα was evaluated by immunohistochemistry (IHC) and flow cytometry in 90 endometrioid and USC samples. The in vitro cytotoxic activity and bystander effect were studied in primary uterine cancer cell lines expressing differential levels of FRα. In vivo antitumor efficacy of IMGN853 was evaluated in xenograft/patient-derived xenograft (PDX) models. Semiquantitative IHC analysis indicated that 41% of the USC patients overexpress FRα. Further, overexpression of FRα (i.e., 2+) was detected via flow cytometry in 22% (2/9) of primary endometrioid and in 27% (3/11) of primary USC cell lines. Increased cytotoxicity was seen with IMGN853 treatment compared with control in 2+ expressing uterine tumor cell lines. In contrast, tumor cell lines with low FRα showed no difference when exposed to IMGN853 versus control. IMGN853 induced bystander killing of FRα = 0 tumor cells. In an endometrioid xenograft model (END(K)265), harboring 2+ FRα, IMGN853 treatment showed complete resolution of tumors ( P USC PDX model (BIO(K)1), expressing 2+ FRα, induced twofold increase in median survival ( P < 0.001). IMGN853 shows impressive antitumor activity in biologically aggressive FRα 2+ uterine cancers. These preclinical data suggest that patients with chemotherapy resistant/recurrent endometrial cancer overexpressing FRα may benefit from this treatment. Mol Cancer Ther; 17(5); 1003-11. ©2018 AACR . ©2018 American Association for Cancer Research.

  11. CONCEPT ANALYSIS: AGGRESSION

    OpenAIRE

    Liu, Jianghong

    2004-01-01

    The concept of aggression is important to nursing because further knowledge of aggression can help generate a better theoretical model to drive more effective intervention and prevention approaches. This paper outlines a conceptual analysis of aggression. First, the different forms of aggression are reviewed, including the clinical classification and the stimulus-based classification. Then the manifestations and measurement of aggression are described. Finally, the causes and consequences of ...

  12. Pulmonary emphysema and tumor microenvironment in primary lung cancer.

    Science.gov (United States)

    Murakami, Junichi; Ueda, Kazuhiro; Sano, Fumiho; Hayashi, Masataro; Nishimoto, Arata; Hamano, Kimikazu

    2016-02-01

    To clarify the relationship between the presence of pulmonary emphysema and tumor microenvironment and their significance for the clinicopathologic aggressiveness of non-small cell lung cancer. The subjects included 48 patients with completely resected and pathologically confirmed stage I non-small cell lung cancer. Quantitative computed tomography was used to diagnose pulmonary emphysema, and immunohistochemical staining was performed to evaluate the matrix metalloproteinase (MMP) expression status in the intratumoral stromal cells as well as the microvessel density (MVD). Positive MMP-9 staining in the intratumoral stromal cells was confirmed in 17 (35%) of the 48 tumors. These 17 tumors were associated with a high MVD, frequent lymphovascular invasion, a high proliferative activity, and high postoperative recurrence rate (all, P pulmonary emphysema (P = 0.02). Lung cancers arising from pulmonary emphysema were also associated with a high MVD, proliferative activity, and postoperative recurrence rate (all, P < 0.05). The MMP-9 expression in intratumoral stromal cells is associated with the clinicopathologic aggressiveness of lung cancer and is predominantly identified in tumors arising in emphysematous lungs. Further studies regarding the biological links between the intratumoral and extratumoral microenvironment will help to explain why lung cancers originating in emphysematous lung tissues are associated with a poor prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Elevated plasma vitamin B12 levels and risk of venous thromboembolism among cancer patients: A population-based cohort study

    DEFF Research Database (Denmark)

    Arendt, Johan Frederik Håkonsen; Farkas, Dora Kormendine; Pedersen, Lars

    2017-01-01

    INTRODUCTION: Both venous thromboembolism (VTE) and high plasma vitamin B12 levels (cobalamin, Cbl) are markers of occult cancer and aggressive cancer with a poor prognosis. In this population-based cohort study, we assessed VTE risk among cancer patients with high plasma Cbl levels. MATERIALS...

  14. The effects of environmental resource and security on aggressive behavior.

    Science.gov (United States)

    Ng, Henry Kin Shing; Chow, Tak Sang

    2017-05-01

    Exposure to different environments has been reported to change aggressive behavior, but previous research did not consider the underlying elements that caused such an effect. Based on previous work on environmental perception, we examined the role of environmental resource and security in altering aggression level. In three experiments, participants were exposed to environments that varied in resource (High vs. Low) and security (High vs. Low) levels, after which aggression was measured. The environments were presented through visual priming (Experiments 1-2) and a first-person gameplay (Experiment 3). We observed a consistent resource-security interaction effect on aggression, operationalized as the level of noise blast (Experiment 1) and number of unpleasant pictures (Experiments 2-3) delivered to strangers by the participants. High resource levels associated with higher aggression in insecure conditions, but lower aggression in secure conditions. The findings suggest that the adaptive value of aggression varies under different environmental constraints. Implications are discussed in terms of the effects of adverse environments on aggression, and the nature's effects on social behavior. Aggr. Behav. 43:304-314, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Sex differences in aggression among children of low and high gender inequality backgrounds: a comparison of gender role and sexual selection theories.

    Science.gov (United States)

    Nivette, Amy E; Eisner, Manuel; Malti, Tina; Ribeaud, Denis

    2014-01-01

    It is well understood in aggression research that males tend to exhibit higher levels of physical aggression than females. Yet there are still a number of gaps in our understanding of variation in sex differences in children's aggression, particularly in contexts outside North America. A key assumption of social role theory is that sex differences vary according to gender polarization, whereas sexual selection theory accords variation to the ecological environment that consequently affects male competition [Archer, J. (2009). Behavioral and Brain Sciences, 32, 249-311; Kenrick, D., & Griskevicious, V. (2009). More holes in social roles [Comment]. Behavioral and Brain Sciences, 32, 283-285]. In the present paper, we explore these contradicting theoretical frameworks by examining data from a longitudinal study of a culturally diverse sample of 863 children at ages 7-13 in Zurich, Switzerland. Making use of the large proportion of children from highly diverse immigrant background we compare the size of the sex difference in aggression between children whose parents were born in countries with low and with high levels of gender inequality. The results show that sex differences in aggression are generally larger among children with parents from high gender inequality backgrounds. However, this effect is small in comparison to the direct effect of a child's biological sex. We discuss implications for future research on sex differences in children's aggression. © 2014 Wiley Periodicals, Inc.

  16. Explaining suicide attempt with personality traits of aggression and impulsivity in a high risk tribal population of India.

    Science.gov (United States)

    Singh, Piyoosh Kumar; Rao, V R

    2018-01-01

    Suicide is a spectrum of behavior including suicide ideation and suicidal attempt and is undoubtedly the outcome of the interaction of several factors. The role of two main constructs of human nature, aggression and impulsivity, has been discussed broadly in relation to suicide, as endophenotypes or traits of personality, in research and in clinical practice across diagnoses. The objective of our study was to assess impulsive and aggressive behaviors among primitive people of the Idu Mishmi tribe, who are known for high suicide completer and attempter rates. The study group was comprised of 177 unrelated Idu Mishmi participants divided into two sets: 39 suicide attempters and 138 non-attempters. Data on demographic factors and details of suicide attempts were collected. Participants completed a set of instruments for assessment of aggression and impulsivity traits. In the Idu Mishimi population we screened (n = 177), 22.03% of the individuals had attempted suicide, a high percentage. The suicide attempters also showed a significant sex difference: 35.9% were male and 64.10% were female (p = .002*). The suicide attempters (A) scored significantly higher than non-attempters (NA) on aggression (A = 23.93,NA = 18.46) and impulsivity (A = 75.53,NA = 71.59, with p value = 0.05). The trait impulsiveness showed a significantly higher difference (F (1, 117) = 7.274) in comparison to aggression (F (1, 117) = 2.647), suggesting a profound role of impulsiveness in suicide attempts in the Idu Mishmi population. Analysis of sub-traits of aggression and impulsivity revealed significant correlations between them. Using different models, multivariate logistic regression implied roles of gender (OR = 1.079 (0.05)) and impulsiveness (OR = 3.355 (0.013)) in suicide attempts. Results demonstrate that gender and impulsivity are strong risk factors for suicide attempts in the Idu Mishmi population.

  17. Explaining suicide attempt with personality traits of aggression and impulsivity in a high risk tribal population of India.

    Directory of Open Access Journals (Sweden)

    Piyoosh Kumar Singh

    Full Text Available Suicide is a spectrum of behavior including suicide ideation and suicidal attempt and is undoubtedly the outcome of the interaction of several factors. The role of two main constructs of human nature, aggression and impulsivity, has been discussed broadly in relation to suicide, as endophenotypes or traits of personality, in research and in clinical practice across diagnoses. The objective of our study was to assess impulsive and aggressive behaviors among primitive people of the Idu Mishmi tribe, who are known for high suicide completer and attempter rates.The study group was comprised of 177 unrelated Idu Mishmi participants divided into two sets: 39 suicide attempters and 138 non-attempters. Data on demographic factors and details of suicide attempts were collected. Participants completed a set of instruments for assessment of aggression and impulsivity traits.In the Idu Mishimi population we screened (n = 177, 22.03% of the individuals had attempted suicide, a high percentage. The suicide attempters also showed a significant sex difference: 35.9% were male and 64.10% were female (p = .002*. The suicide attempters (A scored significantly higher than non-attempters (NA on aggression (A = 23.93,NA = 18.46 and impulsivity (A = 75.53,NA = 71.59, with p value = 0.05. The trait impulsiveness showed a significantly higher difference (F (1, 117 = 7.274 in comparison to aggression (F (1, 117 = 2.647, suggesting a profound role of impulsiveness in suicide attempts in the Idu Mishmi population. Analysis of sub-traits of aggression and impulsivity revealed significant correlations between them. Using different models, multivariate logistic regression implied roles of gender (OR = 1.079 (0.05 and impulsiveness (OR = 3.355 (0.013 in suicide attempts.Results demonstrate that gender and impulsivity are strong risk factors for suicide attempts in the Idu Mishmi population.

  18. High trait aggression in men is associated with low 5-HT levels, as indexed by 5-HT4 receptor binding

    Science.gov (United States)

    Mc Mahon, Brenda; MacDonald Fisher, Patrick; Jensen, Peter Steen; Svarer, Claus; Moos Knudsen, Gitte

    2016-01-01

    Impulsive aggression has commonly been associated with a dysfunction of the serotonin (5-HT) system: many, but not all, studies point to an inverse relationship between 5-HT and aggression. As cerebral 5-HT4 receptor (5-HT4R) binding has recently been recognized as a proxy for stable brain levels of 5-HT, we here test the hypothesis in healthy men and women that brain 5-HT levels, as indexed by cerebral 5-HT4R, are inversely correlated with trait aggression and impulsivity. Sixty-one individuals (47 men) underwent positron emission tomography scanning with the radioligand [11C]SB207145 for quantification of brain 5-HT4R binding. The Buss–Perry Aggression Questionnaire (BPAQ) and the Barratt Impulsiveness Scale were used for assessment of trait aggression and trait impulsivity. Among male subjects, there was a positive correlation between global 5-HT4R and BPAQ total score (P = 0.037) as well as BPAQ physical aggression (P = 0.025). No main effect of global 5-HT4R on trait aggression or impulsivity was found in the mixed gender sample, but there was evidence for sex interaction effects in the relationship between global 5-HT4R and BPAQ physical aggression. In conclusion we found that low cerebral 5-HT levels, as indexed by 5-HT4R binding were associated with high trait aggression in males, but not in females. PMID:26772668

  19. Individual and peer group normative beliefs about relational aggression.

    Science.gov (United States)

    Werner, Nicole E; Hill, Laura G

    2010-01-01

    Studies show that children who use relational aggression process social information in unique ways; however, findings have been inconsistent and limited by methodological weaknesses. This short-term longitudinal study examined developmental changes in 245 (49% female; ages 8-13) 3rd through 8th graders' normative beliefs about relational aggression and tested the hypothesis that individual and classroom-level norms predict relational aggression 1 year later. Results showed that the transition to middle school was marked by increased approval of relational aggression, and individual norms predicted future relational aggression. Importantly, a contextual model showed that students in peer groups highly supportive of relational aggression became increasingly aggressive. Findings extend social information processing theories of relational aggression to focus on the role of peer group cognitions.

  20. Effects of cigarette smoking on human aggressive behavior.

    Science.gov (United States)

    Cherek, D R

    1984-01-01

    Nicotine administered by smoking experimental cigarettes produced decreases in two types of aggressive responses elicited by low and high frequency subtractions of money which were attributed to another "person". The suppressing effects of smoking different doses of nicotine on aggressive responses was dose-dependent, in that smoking the high dose of nicotine produced more suppression than smoking the low dose. The ostensible subtraction of money from another "person", the more aggressive response option available to research subjects, was generally more sensitive to the suppressing effects of nicotine than aggressive noise delivery responses. Although this effect could be attributed to another constituent of tobacco, the dose-dependent effect observed with these cigarettes which contained the same amount of tar suggest the effects are due to nicotine. The relatively selective suppression of aggressive behavior observed in humans in the present study is highly consistent with the effects of nicotine observed in a number of infrahuman species. Nicotine has been found to suppress aggressive behavior in ants (Kostowski 1968), rats (Silverman 1971), and cats (Berntson et. al. 1976). In addition, nicotine has been observed to suppress shock elicited fighting in rats (Driscoll, Baettig 1981; Rodgers 1979; Waldbillig 1980) as well as shock elicited biting in monkeys (Hutchinson, Emley 1973). The importance of determining specificity of drug action on aggressive behavior has been repeatedly emphasized in the field of behavioral pharmacology (Sidman 1959; Cook, Kelleher 1963; Thompson, Boren 1977; Miczek, Krsiak 1979). One method employed to evaluate drug specificity and identify a general non-specific excitatory or depressant drug effect is to determine the drug effect on more than one response option which is available to the subject (Sidman 1959). In this study, the same doses of nicotine which suppressed aggressive responding increased nonaggressive monetary

  1. Targeting cancer cells using 3-bromopyruvate for selective cancer treatment

    Directory of Open Access Journals (Sweden)

    Hussam H Baghdadi

    2017-01-01

    Full Text Available Cancer treatment deserves more research efforts despite intensive conventional treatment modalities for many types of malignancies. Metastasis and resistance to chemotherapy and radiotherapy receive a lot of global research efforts. The current advances in cancer biology may improve targeting the critical metabolic differences that distinguish cancer cells from normal cells. Cancer cells are highly glycolytic for energy production, exhibit the Warburg effect, establish aggressive acidic microenvironment, maintain cancer stem cells, exhibit resistance to chemotherapy, have low antioxidant systems but different ΔΨm (delta psi, mitochondrial transmembrane potential, express P-glycoprotein for multidrug resistance, upregulate glucose transporters and monocarboxylate transporters and are under high steady-state reactive oxygen species conditions. Normal cells differ in all these aspects. Lactate produced through the Warburg effect helps cancer metastasis. Targeting glycolysis reactions for energy production in cancer cells seems promising in decreasing the proliferation and metastasis of cancer cells. 3-bromopyruvate makes use of cancer biology in treating cancer cells, cancer stem cells and preventing metastasis in human cancer as discussed in this review. Updated advances are analyzed here, which include research analysis of background, experience, readings in the field of cancer biology, oncology and biochemistry.

  2. Aggression Profiles in the Spanish Child Population: Differences in Perfectionism, School Refusal and Affect

    Directory of Open Access Journals (Sweden)

    María Vicent

    2018-01-01

    Full Text Available The aim of this study was to identify the existence of combinations of aggression components (Anger, Hostility, Physical Aggression and Verbal Aggression that result in different profiles of aggressive behavior in children, as well as to test the differences between these profiles in scores of perfectionism, school refusal and affect. It is interesting to analyze these variables given: (a their clinical relevance due to their close relationship with the overall psychopathology; and (b the need for further evidence regarding how they are associated with aggressive behavior. The sample consisted of 1202 Spanish primary education students between the ages of 8 and 12. Three aggressive behavior profiles for children were identified using Latent Class Analysis (LCA: High Aggression (Z scores between 0.69 and 0.7, Moderate Aggression (Z scores between −0.39 and −0.47 and Low Aggression (Z scores between −1.36 and −1.58. These profiles were found for 49.08%, 38.46% and 12.48% of the sample, respectively. High Aggression scored significantly higher than Moderate Aggression and Low Aggression on Socially Prescribed Perfectionism (SPP, Self-Oriented Perfectionism (SOP, the first three factors of school refusal (i.e., FI. Negative Affective, FII. Social Aversion and/or Evaluation, FIII. To Pursue Attention, and Negative Affect (NA. In addition, Moderate Aggression also reported significantly higher scores than Low Aggression for the three first factors of school refusal and NA. Conversely, Low Aggression had significantly higher mean scores than High Aggression and Moderate Aggression on Positive Affect (PA. Results demonstrate that High Aggression was the most maladaptive profile having a high risk of psychological vulnerability. Aggression prevention programs should be sure to include strategies to overcome psychological problems that characterize children manifesting high levels of aggressive behavior.

  3. Psychiatric diagnosis and aggression before acute hospitalisation.

    Science.gov (United States)

    Colasanti, A; Natoli, A; Moliterno, D; Rossattini, M; De Gaspari, I F; Mauri, M C

    2008-09-01

    To examine the predictors of aggressive behaviours occurring before acute hospitalisation. We analysed 350 acute admissions to a psychiatric ward during a 12-month period. The diagnoses were formulated according to the DSM IV axis I and II criteria. Aggressive behaviours occurring in the week before admission were retrospectively assessed using the modified overt aggression scale. The patients' clinical and sociodemographic variables, concurrent drug or alcohol abuse, and admission status were recorded at the time of admission. Aggressive and violent behaviours were highly prevalent, respectively, in 45% and 33% of the cases. Violence before admission was independently associated with drug abuse, involuntary admission status, and severe psychopathology. A diagnosis of a psychotic disorder did not increase the risk of aggression or violence, compared to the other psychiatric diagnoses. Personality disorders were significantly more associated to aggressive behaviours than psychotic disorders. The diagnosis of psychotic disorder is a poor predictor of aggression in a sample of psychiatric patients. Other clinical and non-clinical variables are associated to aggression before hospitalisation: they include drug abuse, involuntary admission status, general severity of symptoms, and diagnosis of personality disorder.

  4. Association of Normative Beliefs and Anger with Aggression and Antisocial Behavior in Russian Male Juvenile Offenders and High School Students

    Science.gov (United States)

    Sukhodolsky, Denis G.; Ruchkin, Vladislav V.

    2004-01-01

    Examined the association of anger experience and two types of normative beliefs with physical aggression and nonaggressive antisocial behavior in 361 juvenile offenders and 206 high school students in Russia. All participants were male and ranged in age from 14 to 18 years. Higher frequency of aggressive acts was significantly associated with…

  5. Drivers’ Age, Gender, Driving Experience, and Aggressiveness as Predictors of Aggressive Driving Behaviour

    Directory of Open Access Journals (Sweden)

    Perepjolkina Viktorija

    2011-12-01

    Full Text Available Recent years have seen a growing interest in the problem of aggressive driving. In the presentstudy two demographic variables (gender and age, two non-psychological driving-experiencerelated variables (annual mileage and legal driving experience in years and aggressiveness asa personality trait (including behavioural and affective components as psychological variableof individual differences were examined as potential predictors of aggressive driving. The aimof the study was to find out the best predictors of aggressive driving behaviour. The study wasbased on an online survey, and 228 vehicle drivers in Latvia participated in it. The questionnaireincluded eight-item Aggressive Driving Scale (Bone & Mowen, 2006, short Latvian versionof the Buss-Perry Aggression Questionnaire (AQ; Buss & Perry, 1992, and questions gainingdemographic and driving experience information. Gender, age and annual mileage predictedaggressive driving: being male, young and with higher annual driving exposure were associatedwith higher scores on aggressive driving. Dispositional aggressiveness due to anger componentwas a significant predictor of aggressive diving score. Physical aggression and hostility wereunrelated to aggressive driving. Altogether, the predictors explained a total of 28% of thevariance in aggressive driving behaviour. Findings show that dispositional aggressiveness,especially the anger component, as well as male gender, young age and higher annual mileagehas a predictive validity in relation to aggressive driving. There is a need to extend the scope ofpotential dispositional predictors pertinent to driving aggression.

  6. First-in-human uPAR PET: Imaging of Cancer Aggressiveness

    Science.gov (United States)

    Persson, Morten; Skovgaard, Dorthe; Brandt-Larsen, Malene; Christensen, Camilla; Madsen, Jacob; Nielsen, Carsten H.; Thurison, Tine; Klausen, Thomas Levin; Holm, Søren; Loft, Annika; Berthelsen, Anne Kiil; Ploug, Michael; Pappot, Helle; Brasso, Klaus; Kroman, Niels; Højgaard, Liselotte; Kjaer, Andreas

    2015-01-01

    A first-in-human clinical trial with Positron Emission Tomography (PET) imaging of the urokinase-type plasminogen activator receptor (uPAR) in patients with breast, prostate and bladder cancer, is described. uPAR is expressed in many types of human cancers and the expression is predictive of invasion, metastasis and indicates poor prognosis. uPAR PET imaging therefore holds promise to be a new and innovative method for improved cancer diagnosis, staging and individual risk stratification. The uPAR specific peptide AE105 was conjugated to the macrocyclic chelator DOTA and labeled with 64Cu for targeted molecular imaging with PET. The safety, pharmacokinetic, biodistribution profile and radiation dosimetry after a single intravenous dose of 64Cu-DOTA-AE105 were assessed by serial PET and computed tomography (CT) in 4 prostate, 3 breast and 3 bladder cancer patients. Safety assessment with laboratory blood screening tests was performed before and after PET ligand injection. In a subgroup of the patients, the in vivo stability of our targeted PET ligand was determined in collected blood and urine. No adverse or clinically detectable side effects in any of the 10 patients were found. The ligand exhibited good in vivo stability and fast clearance from plasma and tissue compartments by renal excretion. In addition, high uptake in both primary tumor lesions and lymph node metastases was seen and paralleled high uPAR expression in excised tumor tissue. Overall, this first-in-human study therefore provides promising evidence for safe use of 64Cu-DOTA-AE105 for uPAR PET imaging in cancer patients. PMID:26516369

  7. Oil and resource-backed aggression

    International Nuclear Information System (INIS)

    Colgan, Jeff

    2011-01-01

    A common misperception about oil politics is that it has a uniform, monolithic effect on policy development. This paper argues that in fact the net political effect of oil varies dramatically depending on the nature of the petrostate. It shows that oil income, when combined with revolutionary governments in petrostates, generates strong incentives for foreign policy aggression and international conflict. The aggressiveness of petro-revolutionary states is shown to have consequences in both military and economic spheres of international relations. Militarily, the aggressiveness of this type of state leads to a high rate of armed conflicts. Economically, the aggressiveness of petro-revolutionary states shapes global oil markets and international economic relations. The argument is tested using statistical analysis of international conflicts and economic sanctions. The policy implications are then considered, focusing on the negative global impacts of dependence on oil consumption. - Research highlights: → A radical reconsideration of the link between oil and international conflict is needed. → Resource-backed aggression, not resource-competition, is the major source of conflict. → Petro-revolutionary states instigate 250% more military conflicts than typical states. → Petro-revolutionary states are also more frequently targeted for economic sanctions.

  8. Breast Cancer Vaccines: New Insights

    OpenAIRE

    Benedetti, Rosaria; Dell’Aversana, Carmela; Giorgio, Cristina; Astorri, Roberta; Altucci, Lucia

    2017-01-01

    Breast cancer (BC) is a persistent global challenge for its high frequency in women (although it seldom occurs in men), due to the large diffusion of risk factors and gene mutations, and for its peculiar biology and microenvironment. To date, BC can benefit from different therapeutic strategies involving surgery, ablation, chemotherapy, radiotherapy, and more specific approaches such as hormone therapy and the administration of various substances impairing cancer growth, aggressivity, and rec...

  9. Cancer Stem Cells in Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bao, Qi; Zhao, Yue; Renner, Andrea; Niess, Hanno; Seeliger, Hendrik; Jauch, Karl-Walter; Bruns, Christiane J., E-mail: christiane.bruns@med.uni-muenchen.de [Department of Surgery, Ludwig Maximilian University of Munich, Klinikum Grosshadern, Marchioninistr. 15, D-81377, Munich (Germany)

    2010-08-19

    Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer.

  10. High trait aggression in men is associated with low 5-HT levels, as indexed by 5-HT4 receptor binding.

    Science.gov (United States)

    da Cunha-Bang, Sofi; Mc Mahon, Brenda; Fisher, Patrick MacDonald; Jensen, Peter Steen; Svarer, Claus; Knudsen, Gitte Moos

    2016-04-01

    Impulsive aggression has commonly been associated with a dysfunction of the serotonin (5-HT) system: many, but not all, studies point to an inverse relationship between 5-HT and aggression. As cerebral 5-HT4 receptor (5-HT4R) binding has recently been recognized as a proxy for stable brain levels of 5-HT, we here test the hypothesis in healthy men and women that brain 5-HT levels, as indexed by cerebral 5-HT4R, are inversely correlated with trait aggression and impulsivity. Sixty-one individuals (47 men) underwent positron emission tomography scanning with the radioligand [(11)C]SB207145 for quantification of brain 5-HT4R binding. The Buss-Perry Aggression Questionnaire (BPAQ) and the Barratt Impulsiveness Scale were used for assessment of trait aggression and trait impulsivity. Among male subjects, there was a positive correlation between global 5-HT4R and BPAQ total score (P = 0.037) as well as BPAQ physical aggression (P = 0.025). No main effect of global 5-HT4R on trait aggression or impulsivity was found in the mixed gender sample, but there was evidence for sex interaction effects in the relationship between global 5-HT4R and BPAQ physical aggression. In conclusion we found that low cerebral 5-HT levels, as indexed by 5-HT4R binding were associated with high trait aggression in males, but not in females. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  11. When customers exhibit verbal aggression, employees pay cognitive costs.

    Science.gov (United States)

    Rafaeli, Anat; Erez, Amir; Ravid, Shy; Derfler-Rozin, Rellie; Treister, Dorit Efrat; Scheyer, Ravit

    2012-09-01

    In 4 experimental studies, we show that customer verbal aggression impaired the cognitive performance of the targets of this aggression. In Study 1, customers' verbal aggression reduced recall of customers' requests. Study 2 extended these findings by showing that customer verbal aggression impaired recognition memory and working memory among employees of a cellular communication provider. In Study 3, the ability to take another's perspective attenuated the negative effects of customer verbal aggression on participants' cognitive performance. Study 4 linked customer verbal aggression to quality of task performance, showing a particularly negative influence of aggressive requests delivered by high-status customers. Together, these studies suggest that the effects of even minor aggression from customers can strongly affect the immediate cognitive performance of customer service employees and reduce their task performance. The implications for research on aggression and for the practice of customer service are discussed.

  12. A clitoral verrucous carcinoma in an area of lichen planus has aggressive features.

    Science.gov (United States)

    Tjalma, Wiebren A A; Siozopoulou, Vasiliki; Huizing, Manon T

    2017-01-06

    Verrucous carcinoma of the vulva is extremely rare. It is a slow growing, low malignant variant of a squamous cell carcinoma with a cauliflower appearance. Women with lichen planus have an increased risk of developing vulval cancer. A 79-year-old woman consulted for vulval itching. On clinical examination, a 3-cm large verrucous clitoral cancer in an area of lichen planus was seen. Based on her last clinical examination, the growth was estimated to be 1 cm 2 per month with an invasion depth after 6 months of 5 mm. A tumor developing in an area of lichen planus appears to have more aggressive features. This is the first time that the growth of a verrucous carcinoma has been documented in an area of lichen planus. Clinicians and patients should be aware of the aggressive behavior of cancers developing in areas of lichen planus and adjust their surgical management together with the follow-up strategy.

  13. Skin Cancer of the Head and Neck

    OpenAIRE

    Ouyang, Yun-Hsuan

    2010-01-01

    The majority of skin cancers of the head and neck are nonmelanoma skin cancers (NMSC). Basal cell carcinoma and squamous cell carcinoma are the most frequent types of NMSC. Malignant melanoma is an aggressive neoplasm of skin, and the ideal adjuvant therapy has not yet been found, although various options for treatment of skin cancer are available to the patient and physician, allowing high cure rate and excellent functional and cosmetic outcomes. Sunscreen protection and early evaluation of ...

  14. Ejaculatory frequency and the risk of aggressive prostate cancer: Findings from a case-control study.

    Science.gov (United States)

    Papa, Nathan P; MacInnis, Robert J; English, Dallas R; Bolton, Damien; Davis, Ian D; Lawrentschuk, Nathan; Millar, Jeremy L; Pedersen, John; Severi, Gianluca; Southey, Melissa C; Hopper, John L; Giles, Graham G

    2017-08-01

    Recent literature reports inverse associations with ejaculator frequency and prostate cancer (PC). We sought to explore the relationship between ejaculatory frequency from ages 20 to 50 and subsequent development of aggressive PC. We conducted a case-control study sampling 2,141 men from private urology practices in Victoria, Australia. Cases were defined as men with high grade or high stage PC and controls being biopsy negative men. Ejaculation frequency recalled at age decades 20, 30, and 40 second was assessed by questionnaire. Unconditional multivariable logistic regression models were used to generate odds ratios (ORs). An inverse association with ejaculatory frequency at age 30 to 39 was observed (OR per 5-unit increase per week = 0.83, 95% CI: 0.72-0.96) but not at ages 20 to 29 (OR = 1.01, 95% CI: 0.89-1.14) or ages 40 to 49 (OR = 0.95, 95% CI: 0.81-1.12). This result differed between men with new sexual partners after age 30 (OR = 0.77, P = 0.009) and those with no new partners (OR = 0.97, P = 0.8) though the test for a difference between these estimates was not significant (P = 0.11). We found only weak evidence of an inverse association between ejaculatory frequency in the fourth decade of life and advanced PC, which was not significantly modified by number of new sexual partners. No relationship was found for ejaculatory frequency in the third and fifth decades of life. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. In vivo efficacy of the Bcl-2 antagonist ABT-737 against aggressive Myc-driven lymphomas

    OpenAIRE

    Mason, Kylie D.; Vandenberg, Cassandra J.; Scott, Clare L.; Wei, Andrew H.; Cory, Suzanne; Huang, David C. S.; Roberts, Andrew W.

    2008-01-01

    Deregulated Myc expression drives many human cancers, including Burkitt's lymphoma and a highly aggressive subset of diffuse large cell lymphomas. Myc-driven tumors often display resistance to chemotherapeutics because of acquisition of mutations that impair the apoptosis pathway regulated by the Bcl-2 protein family. Given the need to identify new therapies for such lymphomas, we have evaluated the efficacy of ABT-737, a small molecule that mimics the action of the BH3-only proteins, natural...

  16. Determinants of aggressive behavior: Interactive effects of emotional regulation and inhibitory control.

    Directory of Open Access Journals (Sweden)

    I-Ju Hsieh

    Full Text Available Aggressive behavior can be defined as any behavior intended to hurt another person, and it is associated with many individual and social factors. This study examined the relationship between emotional regulation and inhibitory control in predicting aggressive behavior. Seventy-eight participants (40 males completed self-report measures (Negative Mood Regulation Scale and Buss-Perry Aggression Questionnaire, a stop signal task, and engaged in a modified version of Taylor Aggression Paradigm (TAP exercise, in which the outcome was used as a measure of direct physical aggression. We used a hierarchical, mixed-model multiple regression analysis test to examine the effects of emotion regulation and inhibitory control on physical reactive aggression. Results indicated an interaction between emotion regulation and inhibitory control on aggression. For participants with low inhibitory control only, there was a significant difference between high and low emotion regulation on aggression, such that low emotion regulation participants registered higher aggression than high emotion regulation participants. This difference was not found among participants with high inhibitory control. These results have implications for refining and targeting training and rehabilitation programs aimed at reducing aggressive behavior.

  17. Pathways to romantic relational aggression through adolescent peer aggression and heavy episodic drinking.

    Science.gov (United States)

    Woodin, Erica M; Sukhawathanakul, Paweena; Caldeira, Valerie; Homel, Jacqueline; Leadbeater, Bonnie

    2016-11-01

    Adolescent peer aggression is a well-established correlate of romantic relational aggression; however, the mechanisms underlying this association are unclear. Heavy episodic drinking (or "binge" alcohol use) was examined as both a prior and concurrent mediator of this link in a sample of 282 12-18 year old interviewed four times over 6 years. Path analyses indicated that early peer relational and physical aggression each uniquely predicted later romantic relational aggression. Concurrent heavy episodic drinking fully mediated this effect for peer physical aggression only. These findings highlight two important mechanisms by which peer aggression may increase the risk of later romantic relational aggression: a direct pathway from peer relational aggression to romantic relational aggression and an indirect pathway through peer physical aggression and concurrent heavy episodic drinking. Prevention programs targeting romantic relational aggression in adolescence and young adulthood may benefit from interventions that target multiple domains of risky behavior, including the heavy concurrent use of alcohol. Aggr. Behav. 42:563-576, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Relational Aggression and Physical Aggression among Adolescent Cook Islands Students

    Science.gov (United States)

    Page, Angela; Smith, Lisa F.

    2016-01-01

    Both physical and relational aggression are characterised by the intent to harm another. Physical aggression includes direct behaviours such as hitting or kicking; relational aggression involves behaviours designed to damage relationships, such as excluding others, spreading rumours, and delivering threats and verbal abuse. This study extended…

  19. Longitudinal Relations between Beliefs Supporting Aggression,Anger Regulation, and Dating Aggression among Early Adolescents.

    Science.gov (United States)

    Sullivan, Terri N; Garthe, Rachel C; Goncy, Elizabeth A; Carlson, Megan M; Behrhorst, Kathryn L

    2017-05-01

    Dating aggression occurs frequently in early to mid-adolescence and has negative repercussions for psychosocial adjustment and physical health. The patterns of behavior learned during this developmental timeframe may persist in future dating relationships, underscoring the need to identify risk factors for this outcome. The current study examined longitudinal relations between beliefs supporting aggression, anger regulation, and dating aggression. Participants were 176 middle school students in sixth, seventh, and eighth grade (50 % female; 82 % African American). No direct effects were found between beliefs supporting reactive or proactive aggression and dating aggression. Beliefs supporting reactive aggression predicted increased rates of anger dysregulation, and beliefs supporting proactive aggression led to subsequent increases in anger inhibition. Anger dysregulation and inhibition were associated with higher frequencies of dating aggression. An indirect effect was found for the relation between beliefs supporting reactive aggression and dating aggression via anger dysregulation. Another indirect effect emerged for the relation between beliefs supporting proactive aggression and dating aggression through anger inhibition. The study's findings suggested that beliefs supporting proactive and reactive aggression were differentially related to emotion regulation processes, and identified anger dysregulation and inhibition as risk factors for dating aggression among adolescents.

  20. Cancer Stem Cells in Pancreatic Cancer

    Science.gov (United States)

    Bao, Qi; Zhao, Yue; Renner, Andrea; Niess, Hanno; Seeliger, Hendrik; Jauch, Karl-Walter; Bruns, Christiane J.

    2010-01-01

    Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer. PMID:24281178

  1. Cancer Stem Cells in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Karl-Walter Jauch

    2010-08-01

    Full Text Available Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs. Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer.

  2. Parents' Aggressive Influences and Children's Aggressive Problem Solutions with Peers

    Science.gov (United States)

    Duman, Sarah; Margolin, Gayla

    2007-01-01

    This study examined children's aggressive and assertive solutions to hypothetical peer scenarios in relation to parents' responses to similar hypothetical social scenarios and parents' actual marital aggression. The study included 118 children ages 9 to 10 years old and their mothers and fathers. Children's aggressive solutions correlated with…

  3. Lateralisation of aggressive displays in a tephritid fly

    Science.gov (United States)

    Benelli, Giovanni; Donati, Elisa; Romano, Donato; Stefanini, Cesare; Messing, Russell H.; Canale, Angelo

    2015-02-01

    Lateralisation (i.e. different functional and/or structural specialisations of the left and right sides of the brain) of aggression has been examined in several vertebrate species, while evidence for invertebrates is scarce. In this study, we investigated lateralisation of aggressive displays (boxing with forelegs and wing strikes) in the Mediterranean fruit fly, Ceratitis capitata. We attempted to answer the following questions: (1) do medflies show lateralisation of aggressive displays at the population-level; (2) are there sex differences in lateralisation of aggressive displays; and (3) does lateralisation of aggression enhance fighting success? Results showed left-biased population-level lateralisation of aggressive displays, with no consistent differences among sexes. In both male-male and female-female conflicts, aggressive behaviours performed with left body parts led to greater fighting success than those performed with right body parts. As we found left-biased preferential use of body parts for both wing strikes and boxing, we predicted that the left foreleg/wing is quicker in exploring/striking than the right one. We characterised wing strike and boxing using high-speed videos, calculating mean velocity of aggressive displays. For both sexes, aggressive displays that led to success were faster than unsuccessful ones. However, left wing/legs were not faster than right ones while performing aggressive acts. Further research is needed on proximate causes allowing enhanced fighting success of lateralised aggressive behaviour. This is the first report supporting the adaptive role of lateralisation of aggressive displays in insects.

  4. Linking patient outcome to high throughput protein expression data identifies novel regulators of colorectal adenocarcinoma aggressiveness [v1; ref status: indexed, http://f1000r.es/5ad

    Directory of Open Access Journals (Sweden)

    Christi L. French

    2015-04-01

    Full Text Available A key question in cancer systems biology is how to use molecular data to predict the biological behavior of tumors from individual patients. While genomics data have been heavily used, protein signaling data are more directly connected to biological phenotype and might predict cancer phenotypes such as invasion, metastasis, and patient survival. In this study, we mined publicly available data for colorectal adenocarcinoma from the Cancer Genome Atlas and identified protein expression and signaling changes that are statistically associated with patient outcome. Our analysis identified a number of known and potentially new regulators of colorectal cancer. High levels of insulin growth factor binding protein 2 (IGFBP2 were associated with both recurrence and death, and this was validated by immunohistochemical staining of a tissue microarray for a secondary patient dataset. Interestingly, GATA binding protein 3 (GATA3 was the protein most frequently associated with death in our analysis, and GATA3 expression was significantly decreased in tumor samples from stage I-II deceased patients. Experimental studies using engineered colon cancer cell lines show that exogenous expression of GATA3 decreases three-dimensional colony growth and invasiveness of colon cancer cells but does not affect two-dimensional proliferation. These findings suggest that protein data are useful for biomarker discovery and identify GATA3 as a regulator of colorectal cancer  aggressiveness.

  5. The experience of aggression by female teachers in the workplace

    Directory of Open Access Journals (Sweden)

    D. S. van der Merwe

    2015-10-01

    Full Text Available South Africa is a country with exceptionally high levels of frustration and trauma. Research shows that a third of all people in South Africa are exposed to some kind of violence. This causes insecurity and fear, which creates high levels of stress. High stress levels fuels aggression in the workplace. It was observed that female teachers often experience aggression in the workplace. This has a negative effect on their overall sense of well-being as well as their mental health. A purposive sample was selected through two private schools in Gauteng, South Africa, and consisted of eight female teachers. Data was collected by means of in-depth phenomenological interviews, field notes, naive sketches and observation. One central question was posed to the purposefully selected participants: What is your experience of aggression in your workplace? Thematic coding was used to analyse the data. Three themes were identified: different perceptions influenced female teachers' experience of aggression; the pressure in the school system formed an integral part of the experience of aggression and the experienced effect of aggression on the female teachers.

  6. The experience of aggression by female teachers in the workplace

    Directory of Open Access Journals (Sweden)

    D.S. van der Merwe

    2015-06-01

    Full Text Available South Africa is a country with exceptionally high levels of frustration and trauma. Research shows that a third of all people in South Africa are exposed to some kind of violence. This causes insecurity and fear, which creates high levels of stress. High stress levels fuels aggression in the workplace. It was observed that female teachers often experience aggression in the workplace. This has a negative effect on their overall sense of well-being as well as their mental health. A purposive sample was selected through two private schools in Gauteng, South Africa, and consisted of eight female teachers. Data was collected by means of in-depth phenomenological interviews, field notes, naive sketches and observation. One central question was posed to the purposefully selected participants: What is your experience of aggression in your workplace? Thematic coding was used to analyse the data. Three themes were identified: different perceptions influenced female teachers' experience of aggression; the pressure in the school system formed an integral part of the experience of aggression and the experienced effect of aggression on the female teachers.

  7. Combined effect of Hashimoto's thyroiditis and BRAF(V600E) mutation status on aggressiveness in papillary thyroid cancer.

    Science.gov (United States)

    Kim, Su-jin; Myong, Jun Pyo; Jee, Hyeon-Gun; Chai, Young Jun; Choi, June Young; Min, Hye Sook; Lee, Kyu Eun; Youn, Yeo-Kyu

    2016-01-01

    The purpose of this study was to evaluate the association between Hashimoto's thyroiditis and BRAF(V600E) mutation status in patients with papillary thyroid cancer (PTC) and to determine their combined association with tumor aggressiveness in PTC. A total of 1780 patients with PTC who underwent surgery were enrolled in this study. Simple and multiple analyses were performed to determine the association between Hashimoto's thyroiditis and the BRAF(V600E) mutation in PTC. Hashimoto's thyroiditis was present in 11.5% of patients (204/1780) with PTC. Multiple logistic regressions showed that BRAF(V600E) (odds ratio [OR] = 0.493; 95% confidence interval [CI] = 0.360-0.678) and the female sex (OR = 7.146; 95% CI = 3.408-18.347) were independent factors associated with Hashimoto's thyroiditis in PTC. BRAF(V600E) mutation and the Hashimoto's thyroiditis-negative PTC group were associated with aggressive disease (OR = 3.069; 95% CI = 1.654-5.916). Hashimoto's thyroiditis was associated less frequently with BRAF(V600E) , and frequently with the female sex in patients with PTC. Hashimoto's thyroiditis and BRAF(V600E) status may help to predict clinical outcome of PTC. © 2015 Wiley Periodicals, Inc.

  8. Is popularity associated with aggression toward socially preferred or marginalized targets?

    Science.gov (United States)

    Peets, Kätlin; Hodges, Ernest V E

    2014-08-01

    This study was designed to test whether aggression toward easy or challenging targets is more likely to be associated with popularity. More specifically, we tested two alternative hypotheses with a sample of 224 adolescents (12- and 13-year-olds): (a) whether aggression toward highly disliked peers is associated with popularity (the easy target hypothesis) or (b) whether aggression toward highly liked peers is associated with popularity (the challenging target hypothesis). Support was found only for the challenging target hypothesis. In particular, our results indicate that aggressiveness toward peers who are liked by many others has social benefits in the form of greater popularity (particularly for highly preferred adolescents) without social costs (i.e., is unrelated to social preference). In contrast, aggressiveness toward peers who are disliked by many others is associated with lower social preference but bears no association with popularity. These results highlight the importance of studying contextualized aggression in order to understand the conditions under which aggression is most, and least, likely to be associated with social power and dominance. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. TC-1 (c8orf4) enhances aggressive biologic behavior in lung cancer through the Wnt/β-catenin pathway.

    Science.gov (United States)

    Su, Kai; Huang, Lijun; Li, Wenhai; Yan, Xiaolong; Li, Xiaofei; Zhang, Zhipei; Jin, Faguang; Lei, Jie; Ba, Guangzhen; Liu, Boya; Wang, Xiaoping; Wang, Yunjie

    2013-11-01

    The thyroid cancer-1 (TC-1) or c8orf4 gene encodes a 106-residue naturally disordered protein that has been found to be associated with thyroid, gastric, and breast cancer. A recent study has indicated that the protein functions as a positive regulator in the Wnt/β-catenin signaling pathway in human breast cancer. However, no research has been done in the area of lung cancer. Therefore, the goal of the present study was to confirm the relationship among TC-1, lung cancer, and the Wnt/β-catenin signaling pathway. The expression of TC-1 was immunohistochemically examined in 147 patients with non-small-cell lung cancer. TC-1-overexpressed and silenced A549 cells were infected using lentivirus and MTT cell proliferation analysis, and Matrigel invasion assays and scratch-wound assays were performed to confirm the biologic behavioral changes in different A549 cell subsets. The Wnt/β-catenin signaling pathway, key gene β-catenin, target genes of vascular endothelial growth factor, cyclin D1, matrix metalloproteinase-7, c-myc, and survivin were tested at the mRNA and protein level. TC-1 was detected in 97 of the 147 non-small-cell lung cancer primary tumor specimens, and its expression correlated with the TNM stage and regional lymph node metastasis (P cell line. Furthermore, expression of TC-1 protein affected the Wnt/β-catenin signaling pathway's downstream genes, such as vascular endothelial growth factor and matrix metalloproteinase-7, at the mRNA and protein level. TC-1 expression is associated with aggressive biologic behavior in lung cancer and might coordinate with the Wnt/β-catenin pathway as a positive upstream regulator that induces these behaviors. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Personality and attempted suicide. Analysis of anger, aggression and impulsivity.

    Science.gov (United States)

    Giegling, Ina; Olgiati, Paolo; Hartmann, Annette M; Calati, Raffaella; Möller, Hans-Jürgen; Rujescu, Dan; Serretti, Alessandro

    2009-12-01

    Suicide is one of the leading causes of death worldwide, mortality from suicide being approximately 2%. Attempted suicide appears to be a major risk factor for suicide completion. Anger, aggression and impulsivity are personality traits associated with suicide attempt. In this study we analysed a part of a previously reported sample in order to test anger, impulsivity and temperament/character scales as predictors of aggression and self-aggression in suicide attempters and to compare anger- and aggression-related traits between impulsive and premeditated suicide attempts as well as between violent and non-violent suicide methods. One-hundred-eleven consecutively admitted inpatients with a lifetime history of attempted suicide were assessed for anger (State-Trait Anger Expression Inventory, STAXI), aggression (Questionnaire for Measuring Factors of Aggression, FAF) and temperament/character (Temperament and Character Inventory, TCI). Higher aggression scores, as measured by FAF, were predicted by being male, meeting criteria for borderline personality disorder and having higher angry temperament scores as assessed by STAXI; low cooperativeness was also associated with aggression but not after controlling for STAXI scales. TCI dimensions associated with self-aggression were high harm avoidance, high impulsivity and low self-directedness; state anger, inwardly directed anger and inhibition of aggression were also predictors of self-aggression. In conclusion, impulsivity and harm avoidance have emerged as temperament dimensions independently associated with self-aggressive tendencies in personality. Such interactions could explain the correlation between temperament and suicidality but further research is needed. Anger and self-directedness appear to have some effects on suicide attempt.

  11. Circulating mutational portrait of cancer: manifestation of aggressive clonal events in both early and late stages

    Directory of Open Access Journals (Sweden)

    Meng Yang

    2017-05-01

    are consistent with cancer progression or response to EGFR drug treatment. Conclusions This study demonstrates that ctDNA mutation rates in the key tumor-associated genes are clinical parameters relevant to smoking status and mortality. Mutations in ctDNA may serve as an early detection tool for cancer. This study quantitatively confirms the hypothesis that ctDNAs in circulation is the result of dissemination of aggressive tumor clones and survival of resistant clones. This study supports the use of ctDNA profiling as a less-invasive approach to monitor cancer progression and selection of appropriate drugs during cancer evolution.

  12. SATB1 tethers multiple gene loci to reprogram expression profiledriving breast cancer metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Han, Hye-Jung; Kohwi, Yoshinori; Kohwi-Shigematsu, Terumi

    2006-07-13

    Global changes in gene expression occur during tumor progression, as indicated by expression profiling of metastatic tumors. How this occurs is poorly understood. SATB1 functions as a genome organizer by folding chromatin via tethering multiple genomic loci and recruiting chromatin remodeling enzymes to regulate chromatin structure and expression of a large number of genes. Here we show that SATB1 is expressed at high levels in aggressive breast cancer cells, and is undetectable in non-malignant breast epithelial cells. Importantly, RNAi-mediated removal of SATB1 from highly-aggressive MDA-MB-231 cells altered the expression levels of over 1200 genes, restored breast-like acinar polarity in three-dimensional cultures, and prevented the metastastic phenotype in vivo. Conversely, overexpression of SATB1 in the less-aggressive breast cancer cell line Hs578T altered the gene expression profile and increased metastasis dramatically in vivo. Thus, SATB1 is a global regulator of gene expression in breast cancer cells, directly regulating crucial metastasis-associated genes, including ERRB2 (HER2/NEU), TGF-{beta}1, matrix metalloproteinase 3, and metastasin. The identification of SATB1 as a protein that re-programs chromatin organization and transcription profiles to promote breast cancer metastasis suggests a new model for metastasis and may provide means of therapeutic intervention.

  13. The influence of classroom aggression and classroom climate on aggressive-disruptive behavior.

    Science.gov (United States)

    Thomas, Duane E; Bierman, Karen L; Powers, C J

    2011-01-01

    Research suggests that early classroom experiences influence the socialization of aggression. Tracking changes in the aggressive behavior of 4,179 children from kindergarten to second-grade (ages 5-8), this study examined the impact of 2 important features of the classroom context--aggregate peer aggression and climates characterized by supportive teacher-student interactions. The aggregate aggression scores of children assigned to first-grade classrooms predicted the level of classroom aggression (assessed by teacher ratings) and quality of classroom climate (assessed by observers) that emerged by the end of Grade 1. Hierarchical linear model analyses revealed that first-grade classroom aggression and quality of classroom climate made independent contributions to changes in student aggression, as students moved from kindergarten to second grade. Implications for policy and practice are discussed. © 2011 The Authors. Child Development © 2011 Society for Research in Child Development, Inc.

  14. Descriptive Epidemiology, Molecular Biology and Genetics of Hereditary Prostate Cancer in Denmark

    DEFF Research Database (Denmark)

    Bentzon, Diem Nguyen

    2012-01-01

    A search for markers that can differentiate indolent prostate cancers from more aggressive forms. Assessment of clinical differences between hereditary and sporadicc prostate cancer.......A search for markers that can differentiate indolent prostate cancers from more aggressive forms. Assessment of clinical differences between hereditary and sporadicc prostate cancer....

  15. "Just how graphic are graphic novels?" An examination of aggression portrayals in manga and associations with aggressive behavior in adolescents.

    Science.gov (United States)

    Coyne, Sarah M; Callister, Mark; Stockdale, Laura; Coutts, Holly; Collier, Kevin M

    2015-01-01

    Manga, a type of graphic novel, represent a widely popular literary genre worldwide and are one of the fastest growing areas of the publishing arena aimed at adolescents in the United States. However, to our knowledge, there has been almost no empirical research examining content or effects of reading manga. This article consists of 2 studies. Study 1 represents a content analysis of aggressive behavior in best-selling manga aimed at adolescents. Results revealed that aggression was common and was often portrayed in ways that may influence subsequent behavior. Study 2 examined the relationship between reading manga and aggressive behavior in 223 adolescents. Manga readers were more physically aggressive than non-manga readers and also reported more peer relationships with lonely individuals and smaller groups. In addition, reading manga with particularly high levels of aggression was associated with physical aggression even after controlling for media violence exposure in other media. Implications regarding these findings are discussed.

  16. Intra- Versus Intersex Aggression: Testing Theories of Sex Differences Using Aggression Networks.

    Science.gov (United States)

    Wölfer, Ralf; Hewstone, Miles

    2015-08-01

    Two theories offer competing explanations of sex differences in aggressive behavior: sexual-selection theory and social-role theory. While each theory has specific strengths and limitations depending on the victim's sex, research hardly differentiates between intrasex and intersex aggression. In the present study, 11,307 students (mean age = 14.96 years; 50% girls, 50% boys) from 597 school classes provided social-network data (aggression and friendship networks) as well as physical (body mass index) and psychosocial (gender and masculinity norms) information. Aggression networks were used to disentangle intra- and intersex aggression, whereas their class-aggregated sex differences were analyzed using contextual predictors derived from sexual-selection and social-role theories. As expected, results revealed that sexual-selection theory predicted male-biased sex differences in intrasex aggression, whereas social-role theory predicted male-biased sex differences in intersex aggression. Findings suggest the value of explaining sex differences separately for intra- and intersex aggression with a dual-theory framework covering both evolutionary and normative components. © The Author(s) 2015.

  17. Tumour-associated microglia/macrophages predict poor prognosis in high-grade gliomas and correlate with an aggressive tumour subtype

    DEFF Research Database (Denmark)

    Sørensen, M D; Dahlrot, R H; Boldt, H B

    2018-01-01

    (+) TAMs co-expressed proteins related to tumour aggressiveness including matrix metallopeptidase-14 and hypoxia-inducible factor-1α. CONCLUSIONS: This is the first study to use automated quantitative immunofluorescence to determine the prognostic impact of TAMs. Our results suggest that M2-like TAMs hold......AIMS: Glioblastomas are highly aggressive and treatment resistant. Increasing evidence suggests that tumour-associated macrophages/microglia (TAMs) facilitate tumour progression by acquiring a M2-like phenotype. Our objective was to investigate the prognostic value of TAMs in gliomas using...

  18. Relationship between boys' normative beliefs about aggression and their physical, verbal, and indirect aggressive behaviors.

    Science.gov (United States)

    Lim, Si Huan; Ang, Rebecca P

    2009-01-01

    This study examined the contribution of general normative beliefs about aggression and specific normative beliefs about retaliatory aggression in predicting physical, verbal, and indirect aggressive behaviors. Two hundred and forty-nine Grade 4 and Grade 5 boys completed the Normative Beliefs about Aggression Scale (NOBAGS) and provided self-reports on the frequency of their physical, verbal, and indirect aggressive behaviors. A series of hierarchical multiple regression analyses revealed that general normative beliefs about aggression contributed significantly in predicting all three types of aggressive behaviors. When general normative beliefs about aggression were controlled for, specific normative beliefs about retaliatory aggression against males but not specific normative beliefs about retaliatory aggression against females, contributed significantly to predict physical, verbal, and indirect aggressive behaviors. Implications for intervention programs are discussed.

  19. "Blurred lines?" Sexual aggression and barroom culture.

    Science.gov (United States)

    Graham, Kathryn; Bernards, Sharon; Wayne Osgood, D; Abbey, Antonia; Parks, Michael; Flynn, Andrea; Dumas, Tara; Wells, Samantha

    2014-05-01

    Meeting potential sexual/romantic partners for mutual pleasure is one of the main reasons young adults go to bars. However, not all sexual contacts are positive and consensual, and aggression related to sexual advances is a common experience. Sometimes such aggression is related to misperceptions in making and receiving sexual advances while other times aggression reflects intentional harassment or other sexually aggressive acts. This study uses objective observational research to assess quantitatively gender of initiators and targets and the extent that sexual aggression involves intentional aggression by the initiator, the nature of responses by targets, and the role of third parties and intoxication. We analyzed 258 aggressive incidents involving sexual advances observed as part of a larger study on aggression in large capacity bars and clubs, using variables collected as part of the original research (gender, intoxication, intent) and variables coded from narrative descriptions (invasiveness, persistence, targets' responses, role of third parties). Hierarchical linear modeling analyses were used to account for nesting of incidents in evening and bars. Ninety percent of incidents involved male initiators and female targets, with almost all incidents involving intentional or probably intentional aggression. Targets mostly responded nonaggressively, usually using evasion. Staff rarely intervened; patron third parties intervened in 21% of incidents, usually to help the target but sometimes to encourage the initiator. initiators' level of invasiveness was related to intoxication of the targets, but not their own intoxication, suggesting intoxicated women were being targeted. Sexual aggression is a major problem in bars often reflecting intentional sexual invasiveness and unwanted persistence rather than misperceptions in sexual advances. Prevention needs to focus on addressing masculinity norms of male patrons and staff who support sexual aggression and better

  20. Popularity differentially predicts reactive and proactive aggression in early adolescence.

    Science.gov (United States)

    Stoltz, Sabine; Cillessen, Antonius H N; van den Berg, Yvonne H M; Gommans, Rob

    2016-01-01

    Previous research has indicated that peer popularity is associated with aggressive behavior. However, it is not yet clear whether popularity is uniquely related to different functions of aggression. In this study, we examined associations between peer-perceived popularity, and reactive and proactive aggression using a cross-sectional and a longitudinal design. Yearly sociometric measures of popularity, and reactive and proactive aggression were gathered from 266 seventh and eight grade adolescents (Mage grade 7 = 12.80, SDage  = .40). Popularity was positively correlated with proactive aggression and negatively correlated with reactive aggression, both concurrently as over time. Curvilinear trends indicated that a significant minority of low versus high popular adolescents showed both functions of aggression. Somewhat stronger effects of popularity on proactive aggression were found for boys than girls. Stably popular adolescents showed the highest levels of proactive aggression, whereas stably unpopular youth showed the highest levels of reactive aggression. Implications and directions for future research are discussed. © 2015 Wiley Periodicals, Inc.

  1. Daily Patterns of Stress and Conflict in Couples: Associations with Marital Aggression and Family-of-Origin Aggression

    Science.gov (United States)

    Timmons, Adela C.; Arbel, Reout; Margolin, Gayla

    2016-01-01

    For many married individuals, the ups and downs of daily life are connected such that stressors impacting one person also impact the other person. For example, stress experienced by one individual may “spill over” to negatively impact marital functioning. This study used both partners’ daily diary data to examine same-day and cross-day links between stress and marital conflict and tested several factors that make couples vulnerable to spillover. Assessment of 25 wide-ranging sources of daily stress included both paid and unpaid work, health issues, financial concerns, and having to make difficult decisions. Results showed that both husbands and wives’ experience of total daily stress were associated with greater same-day marital conflict and that conflict was greater on days both spouses experienced high levels of stress. Evidence of cross-day spillover was found only in those couples with high concurrent marital aggression and in couples where wives reported high family-of-origin aggression. These results highlight both the common, anticipated nature of same-day spillover and the potentially problematic aspects of more prolonged patterns representing failure to recover from stressors that occurred the previous day. The discussion focuses on how reactivity in one life domain puts that individual at risk for generating stress in another life domain and how current marital aggression and family-of-origin aggression are associated with difficulty recovering from stressful events. PMID:27504754

  2. Hearing regulates Drosophila aggression.

    Science.gov (United States)

    Versteven, Marijke; Vanden Broeck, Lies; Geurten, Bart; Zwarts, Liesbeth; Decraecker, Lisse; Beelen, Melissa; Göpfert, Martin C; Heinrich, Ralf; Callaerts, Patrick

    2017-02-21

    Aggression is a universal social behavior important for the acquisition of food, mates, territory, and social status. Aggression in Drosophila is context-dependent and can thus be expected to involve inputs from multiple sensory modalities. Here, we use mechanical disruption and genetic approaches in Drosophila melanogaster to identify hearing as an important sensory modality in the context of intermale aggressive behavior. We demonstrate that neuronal silencing and targeted knockdown of hearing genes in the fly's auditory organ elicit abnormal aggression. Further, we show that exposure to courtship or aggression song has opposite effects on aggression. Our data define the importance of hearing in the control of Drosophila intermale aggression and open perspectives to decipher how hearing and other sensory modalities are integrated at the neural circuit level.

  3. Height, selected genetic markers and prostate cancer risk

    DEFF Research Database (Denmark)

    Lophatananon, Artitaya; Stewart-Brown, Sarah; Kote-Jarai, Zsofia

    2017-01-01

    Background:Evidence on height and prostate cancer risk is mixed, however, recent studies with large data sets support a possible role for its association with the risk of aggressive prostate cancer.Methods:We analysed data from the PRACTICAL consortium consisting of 6207 prostate cancer cases...... and 6016 controls and a subset of high grade cases (2480 cases). We explored height, polymorphisms in genes related to growth processes as main effects and their possible interactions.Results:The results suggest that height is associated with high-grade prostate cancer risk. Men with height >180 cm...... are at a 22% increased risk as compared to men with height prostate cancer risk. The aggregate scores of the selected variants identified a significantly increased risk of overall prostate cancer...

  4. Social Information Processing, Experiences of Aggression in Social Contexts, and Aggressive Behavior in Adolescents

    OpenAIRE

    Lösel, Friedrich; Bliesener, Thomas; Bender, Doris

    2013-01-01

    This study examines social information processing and experiences of aggression in social contexts as predictors of different forms of aggressive behavior. A sample of 102 boys (aggressive, average, competent, and victimized students) was investigated with a prospective design in Grade 7/8 and again in Grade 9/10. Results show an aggressive-impulsive response repertoire strongly predicted self-reported and teacher-reported physical aggression, verbal aggression, violent offenses, general aggr...

  5. Recklessness as a hallmark of aggressive cancer.

    Science.gov (United States)

    Noda, Makoto; Takahashi, Chiaki

    2007-11-01

    Cancer recurrence after surgical treatment is a major concern for patients and doctors. Understanding what makes tumors prone to recurrence would be an important step toward its prevention. Accumulating evidence indicates that the level of membrane-associated protease regulator reversion-inducing cysteine-rich protein with Kazal motifs (RECK) expressed in tumor tissue is a good prognostic indicator in several common cancers. Certain members of the matrix metalloproteinase family are often upregulated in advanced cancers and are known to play important roles in tumor angiogenesis, invasion and metastasis. RECK negatively regulates several matrix metalloproteinases. Therefore, RECK itself may well be considered a promising tool or target molecule to be activated in cancer therapy. Here we review the recent advances in RECK research and discuss some of the important issues to be addressed in future studies.

  6. Implicit cognitive aggression among young male prisoners: Association with dispositional and current aggression.

    OpenAIRE

    Ireland, Jane Louise; Adams, Christine

    2015-01-01

    The current study explores associations between implicit and explicit aggression in young adult male prisoners, seeking to apply the Reflection-Impulsive Model and indicate parity with elements of the General Aggression Model and Social Cognition. Implicit cognitive aggressive processing is not an area that has been examined among prisoners. Two hundred and sixty two prisoners completed an implicit cognitive aggression measure (PUZZLE Test) and explicit aggression measures, covering current b...

  7. Squamous cell cancer (image)

    Science.gov (United States)

    Squamous cell cancer involves cancerous changes to the cells of the middle portion of the epidermal skin layer. It is ... malignant tumor, and is more aggressive than basal cell cancer, but still may be relatively slow-growing. It ...

  8. SU-E-J-95: Predicting Treatment Outcomes for Prostate Cancer: Irradiation Responses of Prostate Cancer Stem Cells

    International Nuclear Information System (INIS)

    Wang, K

    2014-01-01

    Purpose: Most prostate cancers are slow-growing diseases but normally require much higher doses (80Gy) with conventional fractionation radiotherapy, comparing to other more aggressive cancers. This study is to disclose the radiobiological basis of this discrepancy by proposing the concept of prostate cancer stem cells (CSCs) and examining their specific irradiation responses. Methods: There are overwhelming evidences that CSC may keep their stemness, e.g. the competency of cell differentiation, in hypoxic microenvironments and hence become radiation resistive, though the probability is tiny for aggressiveness cancers. Tumor hypoxia used to be considered as an independent reason for poor treatment outcomes, and recent evidences showed that even prostate cancers were also hypoxic though they are very slow-growing. In addition, to achieve comparable outcomes to other much more aggressive cancers, much higher doses (rather than lower doses) are always needed for prostate cancers, regardless of its non-aggressiveness. All these abnormal facts can only be possibly interpreted by the irradiation responses characteristics of prostate CSCs. Results: Both normal cancer cells (NCCs) and CSCs exiting in tumors, in which NCCs are mainly for symptoms whereas killing all CSCs achieves disease-free. Since prostate cancers are slow-growing, the hypoxia in prostate cancers cannot possibly from NCCs, thus it is caused by hypoxic CSCs. However, single hypoxic cell cannot be imaged due to limitation of imaging techniques, unless a large group of hypoxic cells exist together, thus most of CSCs in prostate cancers are virtually hypoxic, i.e. not in working mode because CSCs in proliferating mode have to be normoxic, and this explains why prostate cancers are unaggressive. Conclusion: The fractional dose in conventional radiotherapy (∼2Gy) could only kill NCCs and CSCs in proliferating modes, whereas most CSCs survived fractional treatments since they were hypoxic, thus to eliminate all

  9. Media depictions of physical and relational aggression: connections with aggression in young adults' romantic relationships.

    Science.gov (United States)

    Coyne, Sarah M; Nelson, David A; Graham-Kevan, Nicola; Tew, Emily; Meng, K Nathan; Olsen, Joseph A

    2011-01-01

    Various studies have found that viewing physical or relational aggression in the media can impact subsequent engagement in aggressive behavior. However, this has rarely been examined in the context of relationships. Accordingly, the aim of this study was to examine the connection between viewing various types of aggression in the media and perpetration of aggression against a romantic partner. A total of 369 young adults completed a variety of questionnaires asking for their perpetration of various forms of relationship aggression. Participants' exposure to both physical and relational aggression in the media was also assessed. As a whole, we found a relationship between viewing aggression in the media and perpetration of aggression; however, this depended on the sex of the participant and the type of aggression measured. Specifically, exposure to physical violence in the media was related to engagement in physical aggression against their partner only for men. However, exposure to relational aggression in the media was related to romantic relational aggression for both men and women.

  10. Individual Differences in the Extent and Development of Aggressive Cognitive-Associative Networks.

    Science.gov (United States)

    Bushman, Brad J.

    1996-01-01

    Extends L. Berkowitz's neoassociationist aggression model by considering the role of personality variables. Experiment one tested the hypothesis that high-trait-aggressive individuals have more developed aggressive cognitive-associative networks than low-trait-aggressive individuals. In experiment two, participants rated the stimulus words used in…

  11. Reduced expression of α-L-Fucosidase-1 (FUCA-1) predicts recurrence and shorter cancer specific survival in luminal B LN+ breast cancer patients.

    Science.gov (United States)

    Bonin, Serena; Parascandolo, Alessia; Aversa, Cinzia; Barbazza, Renzo; Tsuchida, Nobuo; Castellone, Maria Domenica; Stanta, Giorgio; Vecchio, Giancarlo

    2018-03-16

    The lysosomal enzyme α-L-Fucosidase-1 (FUCA-1) catalyzes the hydrolytic cleavage of terminal fucose residues. FUCA-1 gene is down-regulated in highly aggressive and metastatic human tumors as its inactivation perturbs the fucosylation of proteins involved in cell adhesion, migration and metastases. Negativity to FUCA-1 was significantly related to the development of later recurrences in breast cancer patients with lymph node involvement at diagnosis. Cancer specific survival of luminal B LN+ patients was influenced by FUCA-1 expression as luminal B LN+ patients with positive expression had a longer cancer specific survival. FUCA-1 mRNA expression was inversely related to cancer stage and lymph node involvement. WB and qPCR analysis of FUCA-1 expression in breast cancer-derived cell lines confirmed an inverse relationship with tumor aggressiveness. This study shows that, within LN+ breast cancer patients, FUCA-1 is able to identify a sub-set of non recurrent patients characterized by the positive expression of FUCA-1 and that, within luminal B LN+ patients, the expression of FUCA-1 predicts longer cancer specific survival. We have analyzed FUCA-1 in 305 breast cancer patients by Immunohistochemistry (IHC), and by qPCR in breast cancer patients and in breast cancer cell lines.

  12. The pioneer factor PBX1 is a novel driver of metastatic progression in ERα-positive breast cancer

    Science.gov (United States)

    Magnani, Luca; Patten, Darren K.; Nguyen, Van T.M.; Hong, Sung-Pil; Steel, Jennifer H.; Patel, Naina; Lombardo, Ylenia; Faronato, Monica; Gomes, Ana R.; Woodley, Laura; Page, Karen; Guttery, David; Primrose, Lindsay; Garcia, Daniel Fernandez; Shaw, Jacqui; Viola, Patrizia; Green, Andrew; Nolan, Christopher; Ellis, Ian O.; Rakha, Emad A.; Shousha, Sami; Lam, Eric W.-F.; Győrffy, Balázs; Lupien, Mathieu; Coombes, R. Charles

    2015-01-01

    Over 30% of ERα breast cancer patients develop relapses and progress to metastatic disease despite treatment with endocrine therapies. The pioneer factor PBX1 translates epigenetic cues and mediates estrogen induced ERα binding. Here we demonstrate that PBX1 plays a central role in regulating the ERα transcriptional response to epidermal growth factor (EGF) signaling. PBX1 regulates a subset of EGF-ERα genes highly expressed in aggressive breast tumours. Retrospective stratification of luminal patients using PBX1 protein levels in primary cancer further demonstrates that elevated PBX1 protein levels correlate with earlier metastatic progression. In agreement, PBX1 protein levels are significantly upregulated during metastatic progression in ERα-positive breast cancer patients. Finally we reveal that PBX1 upregulation in aggressive tumours is partly mediated by genomic amplification of the PBX1 locus. Correspondingly, ERα-positive breast cancer patients carrying PBX1 amplification are characterized by poor survival. Notably, we demonstrate that PBX1 amplification can be identified in tumor derived-circulating free DNA of ERα-positive metastatic patients. Metastatic patients with PBX1 amplification are also characterized by shorter relapse-free survival. Our data identifies PBX1 amplification as a functional hallmark of aggressive ERα-positive breast cancers. Mechanistically, PBX1 amplification impinges on several critical pathways associated with aggressive ERα-positive breast cancer. PMID:26215677

  13. Elevated expression of Thoc1 is associated with aggressive phenotype and poor prognosis in colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Chenchen; Yue, Ben; Yuan, Chenwei; Zhao, Senlin; Fang, Changyi; Yu, Yang; Yan, Dongwang, E-mail: yandw70@163.com

    2015-12-04

    The THO complex 1 (Thoc1) is a nuclear matrix protein playing vital roles in transcription elongation and mRNA export. Recently, aberrant expression of Thoc1 has been reported in an increasing array of tumor types. However, the clinical significance of Thoc1 expression in colorectal cancer (CRC) is still unknown. The present study aimed to characterize the expression of Thoc1 in human CRC and evaluate its clinical significance. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analyses showed that the mRNA and protein expression of Thoc1 in CRC specimens was significantly higher than that in adjacent normal colon mucosae. Immunohistochemistry (IHC) was conducted to characterize the expression pattern of Thoc1 in 185 archived paraffin-embedded CRC specimens. Statistical analyses revealed that high levels of Thoc1 expression were associated with the clinical stages and tumor differentiation. CRC patients with high levels of Thoc1 expression had poorer overall-survival and disease-free survival, whereas those with lower levels of Thoc1 expression survived longer. Furthermore, multivariate Cox regression analyses demonstrated that Thoc1 expression remained an independent prognostic factor for increased disease recurrence and decreased survival. Our results suggest for the first time that Thoc1 is involved in the development and progression of CRC, and elevated expression of Thoc1 is associated with aggressive phenotype and poor prognosis in CRC. These findings may prove to be clinically useful for developing a new therapeutic target of CRC treatment.

  14. Aggressiveness Niche: Can It Be the Foster Ground for Cancer Metastasis Precursors?

    Directory of Open Access Journals (Sweden)

    Wael M. ElShamy

    2016-01-01

    Full Text Available The relationship between tumor initiation and tumor progression can follow a linear projection in which all tumor cells are equally endowed with the ability to progress into metastasis. Alternatively, not all tumor cells are equal genetically and/or epigenetically, and only few cells are induced to become metastatic tumor cells. The location of these cells within the tumor can also impact the fate of these cells. The most inner core of a tumor where an elevated pressure of adverse conditions forms, such as necrosis-induced inflammation and hypoxia-induced immunosuppressive environment, seems to be the most fertile ground to generate such tumor cells with metastatic potential. Here we will call this necrotic/hypoxic core the “aggressiveness niche” and will present data to support its involvement in generating these metastatic precursors. Within this niche, interaction of hypoxia-surviving cells with the inflammatory microenvironment influenced by newly recruited mesenchymal stromal cells (MSCs, tumor-associated macrophages (TAMs, and other types of cells and the establishment of bidirectional interactions between them elevate the aggressiveness of these tumor cells. Additionally, immune evasion properties induced in these cells most likely contribute in the formation and maintenance of such aggressiveness niche.

  15. Aggressive angiomyxoma of the thigh

    Energy Technology Data Exchange (ETDEWEB)

    Heffernan, E.J.; Alkubaidan, F.O.; Munk, P.L. [Vancouver General Hospital, Department of Radiology, Vancouver, BC (Canada); University of British Columbia, Vancouver, BC (Canada); Hayes, M.M. [BC Cancer Agency, Department of Pathology, Vancouver, BC (Canada); Clarkson, P.W. [BC Cancer Agency, Department of Surgery, Radiation Oncology and Developmental Radiotherapeutics, Vancouver, BC (Canada)

    2008-07-15

    Aggressive angiomyxoma is a rare tumour that typically occurs in the perineum in women of reproductive age. A small number of cases occurring in men have been reported, all of which were located in the low pelvis, perineum or scrotum. While benign, the tumour is locally infiltrative and consequently has a high rate of local recurrence following surgery; therefore, accurate pre-operative diagnosis is important. The characteristic location of these tumours in the low pelvis or perineum has led to speculation that aggressive angiomyxomas arise from a mesenchymal cell that is unique to the perineum. We describe a case of aggressive angiomyxoma arising in the thigh of a 54-year-old man, which we believe is the first reported instance of this rare neoplasm occurring remote from the pelvis or perineum in a male patient. Cross-sectional imaging demonstrated a well-defined mass that had low density on CT and high intensity on fluid-sensitive MR sequences. Biopsy was non-diagnostic and excision was performed. At histological analysis, the tumour exhibited the characteristic features of aggressive angiomyxoma, with bland spindle cells and large, hyalinised blood vessels in a hypocellular myxoid matrix. Extensive immunohistochemical staining further supported the diagnosis. While the imaging features of these tumours are non-specific and suggestive of myxoid neoplasms, the diagnosis should be considered whenever biopsy of a myxoid-appearing mass yields hypocellular, non-diagnostic material, despite adequate sampling. (orig.)

  16. MRI-derived Restriction Spectrum Imaging Cellularity Index is Associated with High Grade Prostate Cancer on Radical Prostatectomy Specimens

    Directory of Open Access Journals (Sweden)

    Michael Andre Liss

    2015-02-01

    Full Text Available Objectives: We evaluate a novel magnetic resonance imaging (MRI technique to improve detection of aggressive prostate cancer. Methods: We performed a retrospective analysis of presurgical prostate MRI scans using an advanced diffusion weighted imaging technique called Restriction Spectrum Imaging (RSI, which can be presented as a normalized z-score statistic (RSI z-score. Scans were acquired prior to radical prostatectomy. Prostatectomy specimens were processed using whole mount sectioning and regions of interest (ROIs were drawn around individual prostate cancer (PCa tumors. Corresponding ROIs were drawn on the MRI imaging and paired with ROIs in regions with no pathology. RSI z-score and conventional apparent diffusion coefficient (ADC values were recorded for each ROI. Paired t-test, ANOVA and logistic regression analyses were performed.Results: We evaluated 28 patients with 64 regions of interest (28 benign and 36 PCa. The mean difference in RSI z-score (PCa ROI – Benign ROI was 2.17 (SE = 0.11; p <0.001 and in ADC was 551 mm2/sec (SE = 80 mm2/sec; paired t-test, p <0.001. The differences in the means among all groups (benign, primary Gleason 3 and primary Gleason 4 was significant for both RSI z-score (F3,64 = 97.7, p <0.001 and ADC (F3,64 = 13.9, p <0.001. A t-test was performed on only PCa tumor ROIs (n=36 to determine prostate cancer aggressiveness (Gleason 3 vs. Gleason 4 revealing that RSI z-score was still significant (p = 0.03, whereas, ADC values were no longer significant (p = 0.08. In multivariable analysis adjusting for age and race, RSI z-score was associated with PCa aggressiveness (OR 10.3, 95%CI: 1.4-78.0, p=0.02 while ADC trended to significance (p=0.07. Conclusions: The RSI derived normalized cellularity index (RSI z-score is associated with aggressive prostate cancer as determined by pathologic Gleason scores. Further utilization of RSI techniques may serve to enhance standardized reporting systems.

  17. Aggressive behavior

    NARCIS (Netherlands)

    Didden, H.C.M.; Lindsay, W.R.; Lang, R.B.; Sigafoos, J.; Deb, S.; Wiersma, J.; Peters-Scheffer, N.C.; Marschik, P.B.; O'Reilly, M.F.; Lancioni, G.E.; Singh, N.N.

    2016-01-01

    Aggressive behavior is common in individuals with intellectual and developmental disabilities (IDDs), and it is most often targeted for intervention. Psychological, contextual, and biological risk factors may contribute to the risk of aggressive behavior. Risk factors are gender (males), level of

  18. Relational aggression in marriage.

    Science.gov (United States)

    Carroll, Jason S; Nelson, David A; Yorgason, Jeremy B; Harper, James M; Ashton, Ruth Hagmann; Jensen, Alexander C

    2010-01-01

    Drawing from developmental theories of relational aggression, this article reports on a study designed to identify if spouses use relationally aggressive tactics when dealing with conflict in their marriage and the association of these behaviors with marital outcomes. Using a sample of 336 married couples (672 spouses), results revealed that the majority of couples reported that relationally aggressive behaviors, such as social sabotage and love withdrawal, were a part of their marital dynamics, at least to some degree. Gender comparisons of partner reports of their spouse's behavior revealed that wives were significantly more likely to be relationally aggressive than husbands. Structural equation modeling demonstrated that relational aggression is associated with lower levels of marital quality and greater marital instability for both husbands and wives. Implications are drawn for the use of relational aggression theory in the future study of couple conflict and marital aggression. (c) 2010 Wiley-Liss, Inc.

  19. Daily patterns of stress and conflict in couples: Associations with marital aggression and family-of-origin aggression.

    Science.gov (United States)

    Timmons, Adela C; Arbel, Reout; Margolin, Gayla

    2017-02-01

    For many married individuals, the ups and downs of daily life are connected such that stressors impacting one person also impact the other person. For example, stress experienced by one individual may "spill over" to negatively impact marital functioning. This study used both partners' daily diary data to examine same-day and cross-day links between stress and marital conflict and tested several factors that make couples vulnerable to spillover. Assessment of 25 wide-ranging sources of daily stress included both paid and unpaid work, health issues, financial concerns, and having to make difficult decisions. Results showed that both husbands' and wives' experiences of total daily stress were associated with greater same-day marital conflict and that conflict was greater on days both spouses experienced high levels of stress. Evidence of cross-day spillover was found only in those couples with high concurrent marital aggression and in couples where wives reported high family-of-origin aggression. These results highlight both the common, anticipated nature of same-day spillover and the potentially problematic aspects of more prolonged patterns representing failure to recover from stressors that occurred the previous day. The discussion focuses on how reactivity in one life domain puts that individual at risk for generating stress in another life domain and how current marital aggression and family-of-origin aggression are associated with difficulty recovering from stressful events. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  20. Selection of metastatic breast cancer cells based on adaptability of their metabolic state.

    Directory of Open Access Journals (Sweden)

    Balraj Singh

    Full Text Available A small subpopulation of highly adaptable breast cancer cells within a vastly heterogeneous population drives cancer metastasis. Here we describe a function-based strategy for selecting rare cancer cells that are highly adaptable and drive malignancy. Although cancer cells are dependent on certain nutrients, e.g., glucose and glutamine, we hypothesized that the adaptable cancer cells that drive malignancy must possess an adaptable metabolic state and that such cells could be identified using a robust selection strategy. As expected, more than 99.99% of cells died upon glutamine withdrawal from the aggressive breast cancer cell line SUM149. The rare cells that survived and proliferated without glutamine were highly adaptable, as judged by additional robust adaptability assays involving prolonged cell culture without glucose or serum. We were successful in isolating rare metabolically plastic glutamine-independent (Gln-ind variants from several aggressive breast cancer cell lines that we tested. The Gln-ind cells overexpressed cyclooxygenase-2, an indicator of tumor aggressiveness, and they were able to adjust their glutaminase level to suit glutamine availability. The Gln-ind cells were anchorage-independent, resistant to chemotherapeutic drugs doxorubicin and paclitaxel, and resistant to a high concentration of a COX-2 inhibitor celecoxib. The number of cells being able to adapt to non-availability of glutamine increased upon prior selection of cells for resistance to chemotherapy drugs or resistance to celecoxib, further supporting a linkage between cellular adaptability and therapeutic resistance. Gln-ind cells showed indications of oxidative stress, and they produced cadherin11 and vimentin, indicators of mesenchymal phenotype. Gln-ind cells were more tumorigenic and more metastatic in nude mice than the parental cell line as judged by incidence and time of occurrence. As we decreased the number of cancer cells in xenografts, lung metastasis

  1. Selection of Metastatic Breast Cancer Cells Based on Adaptability of Their Metabolic State

    Science.gov (United States)

    Singh, Balraj; Tai, Karen; Madan, Simran; Raythatha, Milan R.; Cady, Amanda M.; Braunlin, Megan; Irving, LaTashia R.; Bajaj, Ankur; Lucci, Anthony

    2012-01-01

    A small subpopulation of highly adaptable breast cancer cells within a vastly heterogeneous population drives cancer metastasis. Here we describe a function-based strategy for selecting rare cancer cells that are highly adaptable and drive malignancy. Although cancer cells are dependent on certain nutrients, e.g., glucose and glutamine, we hypothesized that the adaptable cancer cells that drive malignancy must possess an adaptable metabolic state and that such cells could be identified using a robust selection strategy. As expected, more than 99.99% of cells died upon glutamine withdrawal from the aggressive breast cancer cell line SUM149. The rare cells that survived and proliferated without glutamine were highly adaptable, as judged by additional robust adaptability assays involving prolonged cell culture without glucose or serum. We were successful in isolating rare metabolically plastic glutamine-independent (Gln-ind) variants from several aggressive breast cancer cell lines that we tested. The Gln-ind cells overexpressed cyclooxygenase-2, an indicator of tumor aggressiveness, and they were able to adjust their glutaminase level to suit glutamine availability. The Gln-ind cells were anchorage-independent, resistant to chemotherapeutic drugs doxorubicin and paclitaxel, and resistant to a high concentration of a COX-2 inhibitor celecoxib. The number of cells being able to adapt to non-availability of glutamine increased upon prior selection of cells for resistance to chemotherapy drugs or resistance to celecoxib, further supporting a linkage between cellular adaptability and therapeutic resistance. Gln-ind cells showed indications of oxidative stress, and they produced cadherin11 and vimentin, indicators of mesenchymal phenotype. Gln-ind cells were more tumorigenic and more metastatic in nude mice than the parental cell line as judged by incidence and time of occurrence. As we decreased the number of cancer cells in xenografts, lung metastasis and then primary

  2. Effect of DNA methylation on identification of aggressive prostate cancer.

    Science.gov (United States)

    Alumkal, Joshi J; Zhang, Zhe; Humphreys, Elizabeth B; Bennett, Christina; Mangold, Leslie A; Carducci, Michael A; Partin, Alan W; Garrett-Mayer, Elizabeth; DeMarzo, Angelo M; Herman, James G

    2008-12-01

    Biochemical (prostate-specific antigen) recurrence of prostate cancer after radical prostatectomy remains a major problem. Better biomarkers are needed to identify high-risk patients. DNA methylation of promoter regions leads to gene silencing in many cancers. In this study, we assessed the effect of DNA methylation on the identification of recurrent prostate cancer. We studied the methylation status of 15 pre-specified genes using methylation-specific polymerase chain reaction on tissue samples from 151 patients with localized prostate cancer and at least 5 years of follow-up after prostatectomy. On multivariate logistic regression analysis, a high Gleason score and involvement of the capsule, lymph nodes, seminal vesicles, or surgical margin were associated with an increased risk of biochemical recurrence. Methylation of CDH13 by itself (odds ratio 5.50, 95% confidence interval [CI] 1.34 to 22.67; P = 0.02) or combined with methylation of ASC (odds ratio 5.64, 95% CI 1.47 to 21.7; P = 0.01) was also associated with an increased risk of biochemical recurrence. The presence of methylation of ASC and/or CDH13 yielded a sensitivity of 72.3% (95% CI 57% to 84.4%) and negative predictive value of 79% (95% CI 66.8% to 88.3%), similar to the weighted risk of recurrence (determined from the lymph node status, seminal vesicle status, surgical margin status, and postoperative Gleason score), a powerful clinicopathologic prognostic score. However, 34% (95% CI 21% to 49%) of the patients with recurrence were identified by the methylation profile of ASC and CDH13 rather than the weighted risk of recurrence. The results of our study have shown that methylation of CDH13 alone or combined with methylation of ASC is independently associated with an increased risk of biochemical recurrence after radical prostatectomy even considering the weighted risk of recurrence score. These findings should be validated in an independent, larger cohort of patients with prostate cancer who have

  3. Perceptions of intimacy and friendship reciprocity moderate peer influence on aggression.

    Science.gov (United States)

    Meter, Diana J; Casper, Deborah M; Card, Noel A

    2015-01-01

    Previous research has shown that close friends' influence can exacerbate adolescents' aggressive behavior, but results of studies which examine whether friendships of greater or lesser qualities moderate peer influence effects are inconsistent. The present study tested whether the perception of the positive friendship quality of intimate exchange and friendship reciprocity moderated best friend influence on participant aggression over time. The 243 participants were approximately 12 years old and ethnically diverse. Neither intimate exchange nor reciprocity significantly moderated friend influence on aggression in a simple way, but the interaction of intimate exchange and friendship reciprocity predicted peer influence on participants' aggression over time. Specifically, highly intimate, nonreciprocal best friendships and less intimate, reciprocal best friendships showed greatest influence when friends' proportion of peer nominations for aggression was high. Reciprocity and intimacy should be considered when predicting peer influence on aggression. © 2014 Wiley Periodicals, Inc.

  4. Early Childhood Aggression Trajectories: Associations with Teacher-Reported Problem Behaviour

    Science.gov (United States)

    Wildeboer, Andrea; Thijssen, Sandra; van IJzendoorn, Marinus H.; van der Ende, Jan; Jaddoe, Vincent W. V.; Verhulst, Frank C.; Hofman, Albert; White, Tonya; Tiemeier, Henning; Bakermans-Kranenburg, Marian J.

    2015-01-01

    High and stable levels of aggression and the presence of aggressive behaviour in multiple settings according to different informants are risk factors for later problems. However, these two factors have not been investigated in early childhood. The present study investigates trajectories of parent-reported child aggression from 1.5 up to 6 years of…

  5. Cruel intentions on television and in real life: can viewing indirect aggression increase viewers' subsequent indirect aggression?

    Science.gov (United States)

    Coyne, Sarah M; Archer, John; Eslea, Mike

    2004-07-01

    Numerous studies have shown that viewing violence in the media can influence an individual's subsequent aggression, but none have examined the effect of viewing indirect aggression. This study examines the immediate effect of viewing indirect and direct aggression on subsequent indirect aggression among 199 children ages 11 to 14 years. They were shown an indirect, direct, or no-aggression video and their subsequent indirect aggression was measured by negative evaluation of a confederate and responses to a vignette. Participants viewing indirect or direct aggression gave a more negative evaluation of and less money to a confederate than participants viewing no-aggression. Participants viewing indirect aggression gave less money to the confederate than those viewing direct aggression. Participants viewing indirect aggression gave more indirectly aggressive responses to an ambiguous situation and participants viewing direct aggression gave more directly aggressive responses. This study provides the first evidence that viewing indirect aggression in the media can have an immediate impact on subsequent aggression.

  6. Pregnancy-related venous thromboembolism and risk of occult cancer

    DEFF Research Database (Denmark)

    Tarp Hansen, Anette; Veres, Katalin; Horváth-Puhó, Erzsébet

    2017-01-01

    The cancer risk during the first year after a pregnancy-related venous thromboembolism episode is higher than expected.An aggressive search for cancer in women with pregnancy-related venous thromboembolism is probably not warranted, due to low absolute risk.......The cancer risk during the first year after a pregnancy-related venous thromboembolism episode is higher than expected.An aggressive search for cancer in women with pregnancy-related venous thromboembolism is probably not warranted, due to low absolute risk....

  7. Pregnancy-related venous thromboembolism and risk of occult cancer

    DEFF Research Database (Denmark)

    Hansen, Anette Tarp; Veres, Katalin; Horváth-Puhó, Erzsébet

    2017-01-01

    The cancer risk during the first year after a pregnancy-related venous thromboembolism episode is higher than expected. An aggressive search for cancer in women with pregnancy-related venous thromboembolism is probably not warranted, due to low absolute risk.......The cancer risk during the first year after a pregnancy-related venous thromboembolism episode is higher than expected. An aggressive search for cancer in women with pregnancy-related venous thromboembolism is probably not warranted, due to low absolute risk....

  8. Aggression in Teachers is Related to Role Conflict and Role Ambiguity as Occupational Stress.

    Science.gov (United States)

    Kanchika, Masaru; Iwasaki, Shinichi; Konish, Akihito; Deguchi, Yasuhiko; Kobayashi, Yumi; Nakada, Akihiro; Inoue, Koki

    2015-12-01

    Aggression in the workplace is increasingly recognized as a serious problem, but there are few studies about worker aggression toward outsiders in the workplace. We investigated the association between aggression and occupational stress among teachers. This was a cross-sectional study of 1583 teachers, principals, and vice-principals. Aggression was measured using the Japanese version of the Buss-Perry Aggression Questionnaire (BAQ). The survey respondents were classified into tertiles according to the BAQ score. The high BAQ group was defined as the upper tertile for the BAQ total score (BAQ total score 625). Occupational stress was measured using the Japanese version of the Generic Job Stress Questionnaire. Comparisons among the groups were performed using multiple logistic regression analysis. Of the 1583 respondents, 488 were included in the high BAQ group. After adjusting for demographic and occupational variables, high role conflict and role ambiguity were significantly associated with belonging to the high BAQ group. In subscales of the BAQ, high role conflict and role ambiguity related to high levels of hostility, and physical aggression. Occupational stress such as role conflict and role ambiguity was associated with aggression among teachers. It is necessary to reduce problems which relates to role conflict and role ambiguity for preventing teachers' aggression.

  9. Empathy Inhibits Aggression in Competition: The Role of Provocation, Emotion, and Gender.

    Science.gov (United States)

    Stanger, Nicholas; Kavussanu, Maria; McIntyre, David; Ring, Christopher

    2016-02-01

    Although the empathy-aggression relationship has been well documented, research has yet to establish whether emotions mediate and gender moderates this relationship in athletes, under conditions of low and high provocation. In this experiment, we assigned team-sport athletes to either a high (n = 40) or a low (n = 40) empathy group, and asked them to compete in a reaction-time task against a (fictitious) opponent, under conditions of low and high provocation. Empathy reduced aggression (i.e., intensity of electrical shock administered to the opponent) at low provocation in men, and at both low and high provocation in women. Guilt mediated the effect of empathy on aggression at low provocation in men; anger did not mediate any effects of empathy on aggression. Our findings indicate that the inhibitory effect of empathy on aggression and the mediating role of guilt are moderated by provocation and gender.

  10. Narcissism, Perceived Social Status, and Social Cognition and Their Influence on Aggression

    Science.gov (United States)

    Gumpel, Thomas P.; Wiesenthal, Vered; Söderberg, Patrik

    2015-01-01

    This study had three primary goals: to explore the relationship between narcissism, participant roles, and aggression; to examine the role of gender as a moderating influence on narcissism-based aggression; and to examine how these variables work together to influence aggressive outcomes in a sample of aggressive middle and high school students.…

  11. Nurses' experience and attitudes towards inpatient aggression on psychiatric wards

    Directory of Open Access Journals (Sweden)

    Martina Tomagová

    2016-08-01

    Full Text Available Aim: To determine the incidence rate of forms of inpatient aggression towards nurses who working on psychiatric wards; to identify their attitude to patient aggression, to the factors that condition the occurrence and management of aggression. To determine the differences between nurses in relation to educational training aimed at the issue of patient aggression. Design: Quantitative cross-sectional study. Methods: Selection of respondents was deliberate. The sample comprised 223 nurses with an average of 21.27 (± 11.41 years of clinical practice. Data collection was implemented by means of the self-assessment scales: Violence and Aggression of Patients Scale (VAPS, Attitude Towards Aggression Scale (ATAS, The Management of Aggression and Violence Attitude Scale-Likert (MAVAS-L. Results: 98.58% experienced inpatient aggression in the course of the previous year. Negative attitudes to patient aggression predominated in the sample. Nurses expressed strongest agreement with the idea that internal factors foster patient aggression. Regarding methods of aggression management, nurses expressed strongest agreement with the use of medical therapy and restraints. They held a neutral attitude towards the use of non-physical methods. The age of nurses had an effect on how strongly they agreed with the importance of internal factors in prompting patient aggression and with the use of medical therapy and restraints. Conclusion: A high percentage of nurses have had personal experience of various forms of patient aggression. Negative attitudes to aggression predominated in our sample of nurses, emphasizing the influence of internal factors. The attitude of nurses towards patient aggression influences the selection of aggression management strategies.

  12. Aggression-related brain function assessed with the Point Subtraction Aggression Paradigm in fMRI

    DEFF Research Database (Denmark)

    Skibsted, Anine P; Cunha-Bang, Sofi da; Carré, Justin M

    2017-01-01

    The Point Subtraction Aggression Paradigm (PSAP) measures aggressive behavior in response to provocations. The aim of the study was to implement the PSAP in a functional neuroimaging environment (fMRI) and evaluate aggression-related brain reactivity including response to provocations and associa......The Point Subtraction Aggression Paradigm (PSAP) measures aggressive behavior in response to provocations. The aim of the study was to implement the PSAP in a functional neuroimaging environment (fMRI) and evaluate aggression-related brain reactivity including response to provocations...... and associations with aggression within the paradigm. Twenty healthy participants completed two 12-min PSAP sessions within the scanner. We evaluated brain responses to aggressive behavior (removing points from an opponent), provocations (point subtractions by the opponent), and winning points. Our results showed...... with the involvement of these brain regions in emotional and impulsive behavior. Striatal reactivity may suggest an involvement of reward during winning and stealing points....

  13. Desensitization to media violence: links with habitual media violence exposure, aggressive cognitions, and aggressive behavior.

    Science.gov (United States)

    Krahé, Barbara; Möller, Ingrid; Huesmann, L Rowell; Kirwil, Lucyna; Felber, Juliane; Berger, Anja

    2011-04-01

    This study examined the links between desensitization to violent media stimuli and habitual media violence exposure as a predictor and aggressive cognitions and behavior as outcome variables. Two weeks after completing measures of habitual media violence exposure, trait aggression, trait arousability, and normative beliefs about aggression, undergraduates (N = 303) saw a violent film clip and a sad or a funny comparison clip. Skin conductance level (SCL) was measured continuously, and ratings of anxious and pleasant arousal were obtained after each clip. Following the clips, participants completed a lexical decision task to measure accessibility of aggressive cognitions and a competitive reaction time task to measure aggressive behavior. Habitual media violence exposure correlated negatively with SCL during violent clips and positively with pleasant arousal, response times for aggressive words, and trait aggression, but it was unrelated to anxious arousal and aggressive responding during the reaction time task. In path analyses controlling for trait aggression, normative beliefs, and trait arousability, habitual media violence exposure predicted faster accessibility of aggressive cognitions, partly mediated by higher pleasant arousal. Unprovoked aggression during the reaction time task was predicted by lower anxious arousal. Neither habitual media violence usage nor anxious or pleasant arousal predicted provoked aggression during the laboratory task, and SCL was unrelated to aggressive cognitions and behavior. No relations were found between habitual media violence viewing and arousal in response to the sad and funny film clips, and arousal in response to the sad and funny clips did not predict aggressive cognitions or aggressive behavior on the laboratory task. This suggests that the observed desensitization effects are specific to violent content.

  14. The CD44(high tumorigenic subsets in lung cancer biospecimens are enriched for low miR-34a expression.

    Directory of Open Access Journals (Sweden)

    Saroj K Basak

    Full Text Available Cellular heterogeneity is an integral part of cancer development and progression. Progression can be associated with emergence of cells that exhibit high phenotypic plasticity (including "de-differentiation" to primitive developmental states, and aggressive behavioral properties (including high tumorigenic potentials. We observed that many biomarkers that are used to identify Cancer Stem Cells (CSC can label cell subsets in an advanced clinical stage of lung cancer (malignant pleural effusions, or MPE. Thus, CSC-biomarkers may be useful for live sorting functionally distinct cell subsets from individual tumors, which may enable investigators to hone in on the molecular basis for functional heterogeneity. We demonstrate that the CD44(hi (CD44-high cancer cell subsets display higher clonal, colony forming potential than CD44(lo cells (n=3 and are also tumorigenic (n=2/2 when transplanted in mouse xenograft model. The CD44(hi subsets express different levels of embryonal (de-differentiation markers or chromatin regulators. In archived lung cancer tissues, ALDH markers co-localize more with CD44 in squamous cell carcinoma (n=5/7 than Adeno Carcinoma (n=1/12. MPE cancer cells and a lung cancer cell line (NCI-H-2122 exhibit chromosomal abnormalities and 1p36 deletion (n=3/3. Since miR-34a maps to the 1p36 deletion site, low miR-34a expression levels were detected in these cells. The colony forming efficiency of CD44(hi cells, characteristic property of CSC, can be inhibited by mir-34a replacement in these samples. In addition the highly tumorigenic CD44(hi cells are enriched for cells in the G2 phase of cell cycle.

  15. Psychosocial antecedents and consequences of workplace aggression for hospital nurses.

    Science.gov (United States)

    Demir, Defne; Rodwell, John

    2012-12-01

    To test a full model of the antecedents to and consequences of various forms of workplace aggression, considering psychosocial factors, for hospital nursing staff. Cross-sectional survey design. Two hundred and seven nurses and midwives working across wards within a medium to large Australian hospital completed the survey. The survey response rate was 26.9%. High frequencies of nurses reported exposure to workplace bullying and internal and external emotional abuse violence types. In terms of antecedents, bullying was linked to high negative affectivity (NA), as well as low supervisor support and coworker support. Internal emotional abuse was associated with low levels of these support variables, as well as high outside work support and low job control. External threat of assault was related to high job demands and NA. In terms of consequences, bullying and verbal sexual harassment were linked to increased psychological distress levels. Bullying and internal emotional abuse were related to lowered organizational commitment. Changes in job satisfaction were not found for any of the workplace aggression types. NA was a significant covariate for all analyses examining consequences of aggression. Different combinations of work conditions (job demands-resources) and individual levels of NA predicted certain types of aggression. Further, nurse perceptions of psychological distress and organizational commitment were affected by exposure to several types of aggression, even after controlling for NA as a potential perceptual bias. This study therefore extends previous research on workplace bullying as a stressor to other types of workplace aggression for nurses. The findings highlight factors that are important in considering effective prevention and intervention of workplace aggression among nursing staff, particularly those working in hospital settings. © 2012 Sigma Theta Tau International.

  16. Testing of mechanisms of action of rituximab and clinical results in high-risk patients with aggressive CD20+ lymphoma

    International Nuclear Information System (INIS)

    Jezersek Novakovic, B.; Juznic Setina, T.; Vovk, M.; Kotnik, V.; Novakovic, S.

    2007-01-01

    Rituximab has been applied successfully in the treatment of indolent and aggressive CD20 positive B cell lymphomas, yet the exact in vivo mechanisms of its action have not been unambiguously explained. This study was therefore aimed to confirm the presumed major mechanisms of action of rituximab and concomitantly to assess the effectiveness of first-line chemo immunotherapy in high-risk patients with aggressive CD20 lymphomas. The activity of rituximab was tested in vitro on Raji and SU-DHL-4 cells using the cell proliferation assay and flow cytometry. In the clinical part of the study, 20 high-risk patients with aggressive CD 20 lymphomas were treated with R-CHOP. Only complement-mediated cytotoxicity was observed under the in vitro applied experimental conditions. Neither the direct apoptotic effect nor the antibody-dependent cell-mediated cytotoxicity was detected probably due to a too low concentration of rituximab and a too low ratio of cytotoxic lymphocytes to tumor cells. The treatment outcome in patients was excellent since complete remissions were achieved in 90% of poor-risk patients at the end of primary treatment and 80% of patients were disease-free at 18.5 months median observation period. According to our results, the complement-dependent cytotoxicity is an important mechanism of rituximab action in vitro. To achieve direct apoptosis, higher concentrations than 20 μg/ml of rituximab should be used, while for an effective antibody-dependent cell-mediated cytotoxicity, the ratio of cytotoxic lymphocytes to tumor cells should be higher than 1:1. In the high-risk patients with aggressive CD20 lymphomas, the addition of rituximab to CHOP substantially improves the therapeutic results. (author)

  17. Capecitabine and Oxaliplatin Before, During, and After Radiotherapy for High-Risk Rectal Cancer.

    Science.gov (United States)

    Larsen, Finn Ole; Markussen, Alice; Jensen, Benny V; Fromm, Anne L; Vistisen, Kirsten K; Parner, Vibeke K; Linnemann, Dorte; Hansen, Rasmus H; Johannesen, Helle H; Schou, Jakob V

    2017-06-01

    To evaluate the effect of capecitabine and oxaliplatin before, during, and after radiotherapy for high-risk rectal cancer. Patients with rectum cancer T4 or T3 involving the mesorectal fascia was included in a prospective phase 2 trial. Liver or lung metastases were accepted if the surgeons found them resectable. The patients received 6 weeks of capecitabine and oxaliplatin before chemoradiotherapy (CRT), continued capecitabine and oxaliplatin during radiotherapy, and received 4 weeks of capecitabine and oxaliplatin after CRT. The patients received radiotherapy as intensity-modulated radiotherapy. Total mesorectal excision was planned 8 weeks after CRT. The patients were evaluated with magnetic resonance imaging (MRI) before start of treatment, after 6 weeks of chemotherapy, and again just before the operation. The European Organization for Research and Treatment of Cancer (EORTC) QLQ-CR29 scoring system was used to evaluate adverse events. Fifty-two patients were enrolled between 2009 and 2012. The treatment was well tolerated, with only one death during treatment. Eighty percent of assessable patients experienced response to chemotherapy alone as evaluated by MRI, which increased to 94% after complete oncologic treatment. Forty-nine patients had a total mesorectal excision performed, all with a R0 resection and with a pathologic complete response of 20% for patients with T3 tumor and 7% for patients with T4 tumor. Five patients had metastases at study entry, while 47 patients had locally advanced rectal cancer without metastases. Of these 47 patients, overall survival and progression-free survival at 5 years was 72% and 62%, respectively, with a median follow-up of 60 months. This aggressive approach with capecitabine and oxaliplatin before, during, and after radiotherapy for high-risk rectal cancer is safe and feasible; it also has an impressive response rate as measured by MRI and a promising 5-year overall survival. Copyright © 2016 Elsevier Inc. All rights

  18. Stereotyping to infer group membership creates plausible deniability for prejudice-based aggression.

    Science.gov (United States)

    Cox, William T L; Devine, Patricia G

    2014-02-01

    In the present study, participants administered painful electric shocks to an unseen male opponent who was either explicitly labeled as gay or stereotypically implied to be gay. Identifying the opponent with a gay-stereotypic attribute produced a situation in which the target's group status was privately inferred but plausibly deniable to others. To test the plausible deniability hypothesis, we examined aggression levels as a function of internal (personal) and external (social) motivation to respond without prejudice. Whether plausible deniability was present or absent, participants high in internal motivation aggressed at low levels, and participants low in both internal and external motivation aggressed at high levels. The behavior of participants low in internal and high in external motivation, however, depended on experimental condition. They aggressed at low levels when observers could plausibly attribute their behavior to prejudice and aggressed at high levels when the situation granted plausible deniability. This work has implications for both obstacles to and potential avenues for prejudice-reduction efforts.

  19. Impact of time since diagnosis and mortality rate on cancer-associated venous thromboembolism - the Scandinavian Thrombosis and Cancer (STAC) cohort

    DEFF Research Database (Denmark)

    Blix, Kristine; Gran, Olga V; Severinsen, Marianne T

    2018-01-01

    BACKGROUND: Venous thromboembolism (VTE) is a common complication in cancer, and studies suggest that aggressive cancers harvest the highest risk of VTE. However, competing risk by death may result in over-estimation of VTE risk in cancers with high mortality. Therefore, we estimated the risk...... narrowed for all cancer sites after competing risk by death was taken into account (from 1-10% to 1-4%). CONCLUSION: The risk of VTE by cancer sites was influenced by the mortality rate and the time since cancer diagnosis. Our findings suggest that the cancer itself is a major contributor to VTE risk...... and that competing risk by death should be taken into account when exploring VTE risk in cancer. This article is protected by copyright. All rights reserved....

  20. The General Aggression Model

    NARCIS (Netherlands)

    Allen, Johnie J.; Anderson, Craig A.; Bushman, Brad J.

    The General Aggression Model (GAM) is a comprehensive, integrative, framework for understanding aggression. It considers the role of social, cognitive, personality, developmental, and biological factors on aggression. Proximate processes of GAM detail how person and situation factors influence

  1. Factors associated with resident aggression toward caregivers in nursing homes.

    Science.gov (United States)

    Zeller, Adelheid; Dassen, Theo; Kok, Gerjo; Needham, Ian; Halfens, Ruud J G

    2012-09-01

    Caregivers in nursing homes often experience aggressive behavior of residents. The aim of this study was to explore the caregivers' experiences with aggressive behavior from residents and to identify environmental factors as well as caregiver and resident characteristics related to aggressive behavior in Swiss nursing homes. A retrospective cross-sectional survey was conducted between November 2010 and April 2011 with a sample of caregivers working in various nursing homes in the German-speaking part of Switzerland. In total, 814 caregivers (response rate 51.8%) of 21 nursing homes participated in the study. Data were collected using the German version of the Survey of Violence Experienced by Staff (SOVES-G-R). Standard descriptive statistics were used to describe and summarize the date. To identify risk factors related to the experience of aggression by residents, multilevel logistic regression analysis was applied. The prevalence of participants reporting an aggressive incident during the 12-month period prior to data collection was 81.6%. Of these, 76.5% had experienced verbal aggression, 27.6% threats, and 54.0% physical aggression. The predictive variables in the multiple regression model for physical aggression were: staff education level (odds ratio [OR]= 1.82), gender (OR = 1.82), age ( 45 years: OR = 2.13), and confidence in managing physical aggression (OR = 1.49). The predictive variables for threatening behavior were staff education level (registered nurses vs. non-registered nurses: OR = 1.70; nonstudent vs. student: OR = 1.89) and age ( 45 years: OR = 2.04). Caregivers in nursing homes are at high risk for experiencing aggressive behavior. The identified risk factors are in line with earlier investigations, but some contradictory results also were observed. The high risk for registered nurses exposed to aggressive behavior and the increased risk for caregivers who feel confident in managing aggressive behavior cast a critical light on the content and

  2. Rejection Sensitivity, Jealousy, and the Relationship to Interpersonal Aggression.

    Science.gov (United States)

    Murphy, Anna M; Russell, Gemma

    2018-07-01

    The development and maintenance of interpersonal relationships lead individuals to risk rejection in the pursuit of acceptance. Some individuals are predisposed to experience a hypersensitivity to rejection that is hypothesized to be related to jealous and aggressive reactions within interpersonal relationships. The current study used convenience sampling to recruit 247 young adults to evaluate the relationship between rejection sensitivity, jealousy, and aggression. A mediation model was used to test three hypotheses: Higher scores of rejection sensitivity would be positively correlated to higher scores of aggression (Hypothesis 1); higher scores of rejection sensitivity would be positively correlated to higher scores of jealousy (Hypothesis 2); jealousy would mediate the relationship between rejection sensitivity and aggression (Hypothesis 3). Study results suggest a tendency for individuals with high rejection sensitivity to experience higher levels of jealousy, and subsequently have a greater propensity for aggression, than individuals with low rejection sensitivity. Future research that substantiates a link between hypersensitivity to rejection, jealousy, and aggression may provide an avenue for prevention, education, or intervention in reducing aggression within interpersonal relationships.

  3. The General Aggression Model.

    Science.gov (United States)

    Allen, Johnie J; Anderson, Craig A; Bushman, Brad J

    2018-02-01

    The General Aggression Model (GAM) is a comprehensive, integrative, framework for understanding aggression. It considers the role of social, cognitive, personality, developmental, and biological factors on aggression. Proximate processes of GAM detail how person and situation factors influence cognitions, feelings, and arousal, which in turn affect appraisal and decision processes, which in turn influence aggressive or nonaggressive behavioral outcomes. Each cycle of the proximate processes serves as a learning trial that affects the development and accessibility of aggressive knowledge structures. Distal processes of GAM detail how biological and persistent environmental factors can influence personality through changes in knowledge structures. GAM has been applied to understand aggression in many contexts including media violence effects, domestic violence, intergroup violence, temperature effects, pain effects, and the effects of global climate change. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Haloperidol for long-term aggression in psychosis.

    Science.gov (United States)

    Khushu, Abha; Powney, Melanie J

    2016-11-27

    Psychotic disorders can lead some people to become agitated. Characterised by restlessness, excitability and irritability, this can result in verbal and physically aggressive behaviour - and both can be prolonged. Aggression within the psychiatric setting imposes a significant challenge to clinicians and risk to service users; it is a frequent cause for admission to inpatient facilities. If people continue to be aggressive it can lengthen hospitalisation. Haloperidol is used to treat people with long-term aggression. To examine whether haloperidol alone, administered orally, intramuscularly or intravenously, is an effective treatment for long-term/persistent aggression in psychosis. We searched the Cochrane Schizophrenia Group Trials Register (July 2011 and April 2015). We included randomised controlled trials (RCT) or double blind trials (implying randomisation) with useable data comparing haloperidol with another drug or placebo for people with psychosis and long-term/persistent aggression. One review author (AK) extracted data. For dichotomous data, one review author (AK) calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a fixed-effect model. One review author (AK) assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE. We have no good-quality evidence of the absolute effectiveness of haloperidol for people with long-term aggression. One study randomising 110 chronically aggressive people to three different antipsychotic drugs met the inclusion criteria. When haloperidol was compared with olanzapine or clozapine, skewed data (n=83) at high risk of bias suggested some advantage in terms of scale scores of unclear clinical meaning for olanzapine/clozapine for 'total aggression'. Data were available for only one other outcome, leaving the study early. When compared with other antipsychotic drugs, people allocated to haloperidol were no more likely to leave the study

  5. Genetic mapping of canine fear and aggression.

    Science.gov (United States)

    Zapata, Isain; Serpell, James A; Alvarez, Carlos E

    2016-08-08

    Fear/anxiety and anger/aggression greatly influence health, quality of life and social interactions. They are a huge burden to wellbeing, and personal and public economics. However, while much is known about the physiology and neuroanatomy of such emotions, little is known about their genetics - most importantly, why some individuals are more susceptible to pathology under stress. We conducted genomewide association (GWA) mapping of breed stereotypes for many fear and aggression traits across several hundred dogs from diverse breeds. We confirmed those findings using GWA in a second cohort of partially overlapping breeds. Lastly, we used the validated loci to create a model that effectively predicted fear and aggression stereotypes in a third group of dog breeds that were not involved in the mapping studies. We found that i) known IGF1 and HMGA2 loci variants for small body size are associated with separation anxiety, touch-sensitivity, owner directed aggression and dog rivalry; and ii) two loci, between GNAT3 and CD36 on chr18, and near IGSF1 on chrX, are associated with several traits, including touch-sensitivity, non-social fear, and fear and aggression that are directed toward unfamiliar dogs and humans. All four genome loci are among the most highly evolutionarily-selected in dogs, and each of those was previously shown to be associated with morphological traits. We propose that the IGF1 and HMGA2 loci are candidates for identical variation being associated with both behavior and morphology. In contrast, we show that the GNAT3-CD36 locus has distinct variants for behavior and morphology. The chrX region is a special case due to its extensive linkage disequilibrium (LD). Our evidence strongly suggests that sociability (which we propose is associated with HS6ST2) and fear/aggression are two distinct GWA loci within this LD block on chrX, but there is almost perfect LD between the peaks for fear/aggression and animal size. We have mapped many canine fear and

  6. Institutional climate and aggression in a secure psychiatric setting

    NARCIS (Netherlands)

    Ros, N.; van der Helm, P.; Wissink, I.; Stams, G.J.; Schaftenaar, P.

    2013-01-01

    The number of aggressive incidents committed by patients in (secure) mental health care is high. The present study examined the relation between institutional climate (support, growth, atmosphere, and repression) and aggressive incidents using data of 72 patients in a secure (forensic) mental health

  7. BRCA1-mutated and basal-like breast cancers have similar aCGH profiles and a high incidence of protein truncating TP53 mutations

    NARCIS (Netherlands)

    Holstege, H.; Horlings, H.M.; Velds, A.; Langerod, A.; Borresen-Dale, A.L.; van de Vijver, M.J.; Nederlof, P.M.; Jonkers, J.

    2010-01-01

    ABSTRACT: BACKGROUND: Basal-like breast cancers (BLBC) are aggressive breast cancers for which, so far, no targeted therapy is available because they typically lack expression of hormone receptors and HER2. Phenotypic features of BLBCs, such as clinical presentation and early age of onset, resemble

  8. Longitudinal Examination of Aggression and Study Skills from Middle to High School: Implications for Dropout Prevention

    Science.gov (United States)

    Orpinas, Pamela; Raczynski, Katherine; Hsieh, Hsien-Lin; Nahapetyan, Lusine; Horne, Arthur M.

    2018-01-01

    Background: High school completion provides health and economic benefits. The purpose of this study is to describe dropout rates based on longitudinal trajectories of aggression and study skills using teacher ratings. Methods: The sample consisted of 620 randomly selected sixth graders. Every year from Grade 6 to 12, a teacher completed a…

  9. Swedish National Registry of Urinary Bladder Cancer: No difference in relative survival over time despite more aggressive treatment.

    Science.gov (United States)

    Jahnson, Staffan; Hosseini Aliabad, Abolfazl; Holmäng, Sten; Jancke, Georg; Liedberg, Fredrik; Ljungberg, Börje; Malmström, Per-Uno; Rosell, Johan

    2016-01-01

    The aim of this study was to use the Swedish National Registry of Urinary Bladder Cancer (SNRUBC) to investigate changes in patient and tumour characteristics, management and survival in bladder cancer cases over a period of 15 years. All patients with newly detected bladder cancer reported to the SNRUBC during 1997-2011 were included in the study. The cohort was divided into three groups, each representing 5 years of the 15 year study period. The study included 31,266 patients (74% men, 26% women) with a mean age of 72 years. Mean age was 71.7 years in the first subperiod (1997-2001) and 72.5 years in the last subperiod (2007-2011). Clinical T categorization changed from the first to the last subperiod: Ta from 45% to 48%, T1 from 21.6% to 22.4%, and T2-T4 from 27% to 25%. Also from the first to the last subperiod, intravesical treatment after transurethral resection for T1G2 and T1G3 tumours increased from 15% to 40% and from 30% to 50%, respectively, and cystectomy for T2-T4 tumours increased from 30% to 40%. No differences between the analysed subperiods were found regarding relative survival in patients with T1 or T2-T4 tumours, or in the whole cohort. This investigation based on a national bladder cancer registry showed that the age of the patients at diagnosis increased, and the proportion of muscle-invasive tumours decreased. The treatment of all tumour stages became more aggressive but relative survival showed no statistically significant change over time.

  10. The Role of Religiosity in African American Preadolescent Aggression

    Science.gov (United States)

    Holmes, Khiela J.; Lochman, John E.

    2012-01-01

    This study examined the role of parent and preadolescent religiosity in aggression among African American preadolescents with moderate to high aggression. Hierarchical regression analyses were used to determine (a) which aspects of parent and preadolescent religiosity (i.e., church attendance, private religious activities, and intrinsic…

  11. Bladder cancer exosomes contain EDIL-3/Del1 and facilitate cancer progression.

    Science.gov (United States)

    Beckham, Carla J; Olsen, Jayme; Yin, Peng-Nien; Wu, Chia-Hao; Ting, Huei-Ju; Hagen, Fred K; Scosyrev, Emelian; Messing, Edward M; Lee, Yi-Fen

    2014-08-01

    High grade bladder cancer is an extremely aggressive malignancy associated with high rates of morbidity and mortality. Understanding how exosomes may affect bladder cancer progression could reveal novel therapeutic targets. Exosomes derived from human bladder cancer cell lines and the urine of patients with high grade bladder cancer were assessed for the ability to promote cancer progression in standard assays. Exosomes purified from the high grade bladder cancer cell line TCC-SUP and the nonmalignant urothelial cell line SV-HUC were submitted for mass spectrometry analysis. EDIL-3 was identified and selected for further analysis. Western blot was done to determine EDIL-3 levels in urinary exosomes from patients with high grade bladder cancer. shRNA gene knockdown and recombinant EDIL-3 were applied to study EDIL-3 function. Exosomes isolated from high grade bladder cancer cells and the urine of patients with high grade bladder cancer promoted angiogenesis and migration of bladder cancer cells and endothelial cells. We silenced EDIL-3 expression and found that shEDIL-3 exosomes did not facilitate angiogenesis, and urothelial and endothelial cell migration. Moreover, exosomes purified from the urine of patients with high grade bladder cancer contained significantly higher EDIL-3 levels than exosomes from the urine of healthy controls. EDIL-3 activated epidermal growth factor receptor signaling while blockade of epidermal growth factor receptor signaling abrogated this EDIL-3 induced bladder cell migration. Exosomes derived from the urine of patients with bladder cancer contains bioactive molecules such as EDIL-3. Identifying these components and their associated oncogenic pathways could lead to novel therapeutic targets and treatment strategies. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  12. Aggression in Psychiatric Wards

    DEFF Research Database (Denmark)

    Hvidhjelm, Jacob; Sestoft, Dorte; Skovgaard, Lene Theil

    2016-01-01

    Health care workers are often exposed to violence and aggression in psychiatric settings. Short-term risk assessments, such as the Brøset Violence Checklist (BVC), are strong predictors of such aggression and may enable staff to take preventive measures against aggression. This study evaluated...

  13. The theory of planned behavior, materialism, and aggressive driving.

    Science.gov (United States)

    Efrat, Kalanit; Shoham, Aviv

    2013-10-01

    Aggressive driving is a growing problem worldwide. Previous research has provided us with some insights into the characteristics of drivers prone to aggressiveness on the road and into the external conditions triggering such behavior. Little is known, however, about the personality traits of aggressive drivers. The present study proposes planned behavior and materialism as predictors of aggressive driving behavior. Data was gathered using a questionnaire-based survey of 220 individuals from twelve large industrial organizations in Israel. Our hypotheses were tested using structural equation modeling. Our results indicate that while planned behavior is a good predictor of the intention to behave aggressively, it has no impact on the tendency to behave aggressively. Materialism, however, was found to be a significant indicator of aggressive driving behavior. Our study is based on a self-reported survey, therefore might suffer from several issues concerning the willingness to answer truthfully. Furthermore, the sampling group might be seen as somewhat biased due to the relatively high income/education levels of the respondents. While both issues, aggressive driving and the theory of planned behavior, have been studied previously, the linkage between the two as well as the ability of materialism to predict aggressive behavior received little attention previously. The present study encompasses these constructs providing new insights into the linkage between them. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Suicide Risk, Aggression and Violence in Major Psychiatric Disorders

    Directory of Open Access Journals (Sweden)

    G Mousavi

    2004-02-01

    Full Text Available Background: Aggression, violence and Suicide are important problems of mental health in our society. They almost always cause disability, death, or other social problems. Appropriate measures can be taken if the distribution of behaviors and suicide risk are well studied in various psychiatric disorders. Methods: This was a cross-sectional study. We studied 801 psychiatric patients who were admitted in a psychiatric emergency unit in Isfahan, Iran, for aggression, violence and risk of suicide. Information was obtained from a 30-item questionnaire, filled by the same physician. Results: About one-third of patients had aggression and/or violence on admission or during hours before it. It was most prevalent in men of 12-26 years old and in bipolar mood disorder patients. "High suicide risk" was markedly found in patients with major depressive disorder. Differences of these phenomena were statistically Conclusion: Our findings show a higher rate of aggression and violence in emergency psychiatric patients than in studies done in other countries. It may be due to higher prevalence of bipolar patients in the study field. The finding of "High suicidal risk" in major depression patients warrent systematic preventive programs. Keywords: Suicide risk, Aggression, Violence

  15. Breast cancer and HIV in the era of highly active antiretroviral therapy: two case reports and review of the literature.

    Science.gov (United States)

    Latif, Naeem; Rana, Fauzia; Guthrie, Troy

    2011-01-01

    The incidence of human immunodeficiency virus (HIV) infection is rising in US women; however its impact on breast cancer incidence, stage at presentation, response and treatment toxicity remains unknown. To address the impact of HIV infection and use of highly active antiretroviral therapy (HAART) on the natural history of breast cancer we present two cases of breast cancer in HIV-infected women and also review the literature. A literature search was done on Medline using the key words HIV/AIDS, breast cancer, and HAART therapy, restricted to English language. There were mostly case reports and one large series of 20 cases reported by Hurley et al. Data concerning the impact of HIV infection and HAART therapy regarding pathogenesis, stage at presentation, tumor type, response, and toxicity associated with treatment were reviewed. The literature review shows that the breast cancer incidence is either same or less in HIV-infected patients compared to the general population. However, the patients with HIV infection present with more advanced stage and aggressive disease, and they also have poor chemotherapy tolerance. The impact of HAART on breast cancer incidence in HIV-infected patients is still unclear. © 2010 Wiley Periodicals, Inc.

  16. Impulsivity, aggression and suicide risk among male schizophrenia patients.

    Science.gov (United States)

    Iancu, Iulian; Bodner, Ehud; Roitman, Suzana; Piccone Sapir, Anna; Poreh, Amir; Kotler, Moshe

    2010-01-01

    Impulsivity has been shown to be a major variable in the etiology of suicide and aggression, but has not been researched as much in the schizophrenic population, which is characterized by serious suicide and aggression risks. 68 male schizophrenia patients responded to a battery of measures including the Positive and Negative Syndrome Scale (PANSS), the impulsivity control scale (IS), the Suicide Risk Scale (SRS) and the Overt Aggression Scale. We divided our subjects into those who received scores above and below the median on the IS. The high-impulsivity group had higher present and past rates of suicidal ideation and showed a trend for more lifetime suicidal attempts than the low-impulsivity group. The impulsivity score correlated positively with the SRS score and with some of the scores of the PANSS (the positive symptoms score, the general psychopathology score and the total score). A multiple regression analysis revealed that an older age, higher levels of aggression, high impulsivity and an elevated score on the general psychopathology subscale of the PANSS contributed positively and significantly to the explained variance of the SRS. Our study supports the contention that high impulsivity in schizophrenia patients is significant in the etiology of suicide in schizophrenia. However, the relationship between impulsivity and aggression in schizophrenia patients, and also the amelioration of impulsivity by pharmacological interventions, require further study. Copyright (c) 2010 S. Karger AG, Basel.

  17. Determinants of Aggressive Tax Avoidance

    OpenAIRE

    Herbert, Tanja

    2015-01-01

    This thesis consists of three essays examining determinants of aggressive tax avoidance. The first essay “Measuring the Aggressive Part of International Tax Avoidance”, co-authored with Prof. Dr. Michael Overesch, proposes a new measure that isolates the additional or even aggressive part in international tax avoidance and analyzes the determinants of aggressive tax avoidance of multinational enterprises. The second essay “Capital Injections and Aggressive Tax Planning - Can Banks Have It All...

  18. Merkel Cell Polyomavirus: A New DNA Virus Associated with Human Cancer.

    Science.gov (United States)

    MacDonald, Margo; You, Jianxin

    2017-01-01

    Merkel cell polyomavirus (MCPyV or MCV) is a novel human polyomavirus that has been discovered in Merkel cell carcinoma (MCC), a highly aggressive skin cancer. MCPyV infection is widespread in the general population. MCPyV-associated MCC is one of the most aggressive skin cancers, killing more patients than other well-known cancers such as cutaneous T-cell lymphoma and chronic myelogenous leukemia (CML). Currently, however, there is no effective drug for curing this cancer. The incidence of MCC has tripled over the past two decades. With the widespread infection of MCPyV and the increase in MCC diagnoses, it is critical to better understand the biology of MCPyV and its oncogenic potential. In this chapter, we summarize recent discoveries regarding MCPyV molecular virology, host cellular tropism, mechanisms of MCPyV oncoprotein-mediated oncogenesis, and current therapeutic strategies for MCPyV-associated MCC. We also present epidemiological evidence for MCPyV infection in HIV patients and links between MCPyV and non-MCC human cancers.

  19. New materialist analyses of virtual gaming, distributed violence, and relational aggression

    DEFF Research Database (Denmark)

    Søndergaard, Dorte Marie

    2016-01-01

    Concerns about children’s and teenager’s use of computer games and their access to films with a high level of violence, coupled with concerns about the possible transfer of aggression from media to children are widespread. However, the question is whether aggression among children and youth...... with these theories and interviews with two boys aged 9 and 11 about their everyday lives in and outside of schools, I investigate where violence and aggression move in children’s everyday lives, how flows of violence and aggression intra-act, and what feeds into them. I further discuss which kinds of aggression...

  20. Aggressive periodontitis: case definition and diagnostic criteria.

    Science.gov (United States)

    Albandar, Jasim M

    2014-06-01

    Aggressive periodontitis is a destructive disease characterized by the following: the involvement of multiple teeth with a distinctive pattern of periodontal tissue loss; a high rate of disease progression; an early age of onset; and the absence of systemic diseases. In some patients periodontal tissue loss may commence before puberty, whereas in most patients the age of onset is during or somewhat after the circumpubertal period. Besides infection with specific microorganisms, a host predisposition seems to play a key role in the pathogenesis of aggressive periodontitis, as evidenced by the familial aggregation of the disease. In this article we review the historical background of the diagnostic criteria of aggressive periodontitis, present a contemporary case definition and describe the clinical parameters of the disease. At present, the diagnosis of aggressive periodontitis is achieved using case history, clinical examination and radiographic evaluation. The data gathered using these methods are prone to relatively high measurement errors. Besides, this diagnostic approach measures past disease history and may not reliably measure existing disease activity or accurately predict future tissue loss. A diagnosis is often made years after the onset of the disease, partly because current assessment methods detect established disease more readily and reliably than they detect incipient or initial lesions where the tissue loss is minimal and usually below the detection threshold of present examination methods. Future advancements in understanding the pathogenesis of this disease may contribute to an earlier diagnosis. Insofar, future case definitions may involve the identification of key etiologic and risk factors, combined with high-precision methodologies that enable the early detection of initial lesions. This may significantly enhance the predictive value of these tests and detect cases of aggressive periodontitis before significant tissue loss develops. © 2014

  1. KIF20A-Mediated RNA Granule Transport System Promotes the Invasiveness of Pancreatic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Keisuke Taniuchi

    2014-12-01

    Full Text Available Pancreatic cancers are aggressive because they are highly invasive and highly metastatic; moreover, effective treatments for aggressive pancreatic cancers are lacking. Here, we report that the motor kinesin protein KIF20A promoted the motility and invasiveness of pancreatic cancer cells through transporting the RNA-binding protein IGF2BP3 and IGF2BP3-bound transcripts toward cell protrusions along microtubules. We previously reported that IGF2BP3 and its target transcripts are assembled into cytoplasmic stress granules of pancreatic cancer cells, and that IGF2BP3 promotes the motility and invasiveness of pancreatic cancer cells through regulation of localized translation of IGF2BP3-bound transcripts in cell protrusions. We show that knockdown of KIF20A inhibited accumulation of IGF2BP3-containing stress granules in cell protrusions and suppressed local protein expression from specific IGF2BP3-bound transcripts, ARF6 and ARHGEF4, in the protrusions. Our results provide insight into the link between regulation of KIF20A-mediated trafficking of IGF2BP3-containing stress granules and modulation of the motility and invasiveness in pancreatic cancers.

  2. Leadership, Cohesion, and Team Norms Regarding Cheating and Aggression.

    Science.gov (United States)

    Shields, David Lyle Light; And Others

    1995-01-01

    Study explored leadership, cohesion, and demographic variables in relation to team norms about cheating and aggression. Surveys of high school and college ball players indicated that older age, higher year in school, and more years playing ball correlated positively with expectations of peer cheating and aggression. (SM)

  3. The relationships among perceived peer acceptance of sexual aggression, punishment certainty, and sexually aggressive behavior.

    Science.gov (United States)

    Strang, Emily; Peterson, Zoë D

    2013-12-01

    Researching the correlates of men's sexually aggressive behavior (i.e., verbal coercion and rape) is critical to both understanding and preventing sexual aggression. This study examined 120 men who completed an anonymous online questionnaire. The study aimed to determine the relative importance of two potential correlates of men's self-reported use of sexual aggression: (a) perceptions that male peers use and support sexual aggression and (b) perceptions of punishment likelihood associated with sexual aggression. Results revealed that perceptions of male friends' acceptance of sexual aggression were strongly associated with individual men's reports of using verbal coercion and rape. Perceptions of punishment likelihood were negatively correlated with verbal coercion but not with rape through intoxication and force. Implications for sexual aggression prevention are discussed.

  4. The oncogenic role of the In1-ghrelin splicing variant in prostate cancer aggressiveness.

    Science.gov (United States)

    Hormaechea-Agulla, Daniel; Gahete, Manuel D; Jiménez-Vacas, Juan M; Gómez-Gómez, Enrique; Ibáñez-Costa, Alejandro; L-López, Fernando; Rivero-Cortés, Esther; Sarmento-Cabral, André; Valero-Rosa, José; Carrasco-Valiente, Julia; Sánchez-Sánchez, Rafael; Ortega-Salas, Rosa; Moreno, María M; Tsomaia, Natia; Swanson, Steve M; Culler, Michael D; Requena, María J; Castaño, Justo P; Luque, Raúl M

    2017-08-29

    The Ghrelin-system is a complex, pleiotropic family composed of several peptides, including native-ghrelin and its In1-ghrelin splicing variant, and receptors (GHSR 1a/b), which are dysregulated in various endocrine-related tumors, where they associate to pathophysiological features, but the presence, functional role, and mechanisms of actions of In1-ghrelin splicing variant in prostate-cancer (PCa), is completely unexplored. Herein, we aimed to determine the presence of key ghrelin-system components (native-ghrelin, In1-ghrelin, GHSR1a/1b) and their potential pathophysiological role in prostate cancer (PCa). In1-ghrelin and native-ghrelin expression was evaluated by qPCR in prostate tissues from patients with high PCa-risk (n = 52; fresh-tumoral biopsies), and healthy-prostates (n = 12; from cystoprostatectomies) and correlated with clinical parameters using Spearman-test. In addition, In1-ghrelin and native-ghrelin was measured in plasma from an additional cohort of PCa-patients with different risk levels (n = 30) and control-healthy patients (n = 20). In vivo functional (proliferation/migration) and mechanistic (gene expression/signaling-pathways) assays were performed in PCa-cell lines in response to In1-ghrelin and native-ghrelin treatment, overexpression and/or silencing. Finally, tumor progression was monitored in nude-mice injected with PCa-cells overexpressing In1-ghrelin, native-ghrelin and empty vector (control). In1-ghrelin, but not native-ghrelin, was overexpressed in high-risk PCa-samples compared to normal-prostate (NP), and this expression correlated with that of PSA. Conversely, GHSR1a/1b expression was virtually absent. Remarkably, plasmatic In1-ghrelin, but not native-ghrelin, levels were also higher in PCa-patients compared to healthy-controls. Furthermore, In1-ghrelin treatment/overexpression, and to a much lesser extent native-ghrelin, increased aggressiveness features (cell-proliferation, migration and PSA secretion) of NP and PCa

  5. Kindergarten children’s genetic vulnerabilities interact with friends’ aggression to promote children’s own aggression

    NARCIS (Netherlands)

    van Lier, P.A.C.; Boivin, M.E.; Vitaro, F.; Brendgen, M.; Koot, H.M.; Dionne, G.; Tremblay, R.E.; Pérusse, D.

    2007-01-01

    OBJECTIVE: To examine whether kindergarten children's genetic liability to physically aggress moderates the contribution of friends' aggression to their aggressive behaviors. METHOD: Teacher and peer reports of aggression were available for 359 6-year-old twin pairs (145 MZ, 212 DZ) as well as

  6. Alcohol, aggression, and violence

    Directory of Open Access Journals (Sweden)

    Darja Škrila

    2005-09-01

    Full Text Available Background: The association between alcohol and aggression has long been recognized, but the systematic research to understand the causal basis for this relationship and the processes that underlie it has only been undertaken in the past 25 years. In the article the most important mechanisms, by which alcohol affects behavior, are explained. Aggression in persons with alcohol dependence and the connection between antisocial (dissocial personality disorder, alcohol and aggression are described. In addition different forms of aggression or violence, that have been committed under the influence of alcohol, such as inter-partner violence, sexual assault, child abuse, crime and traffic accidents are described.Conclusions: The research findings can be used in the prevention and treatment of alcohol-related aggression.

  7. Utilization of Superheroes Social Skills to Reduce Disruptive and Aggressive Behavior

    Science.gov (United States)

    O'Handley, Roderick D.; Radley, Keith C.; Cavell, Hannah J.

    2016-01-01

    The current pilot study investigated the effectiveness of the Superheroes Social Skills program in decreasing disruptive and aggressive behavior of elementary-age students with high-incidence disabilities. Six students in a self-contained classroom, identified as displaying high rates of disruptive and aggressive behavior toward peers, were…

  8. Facing aggression: cues differ for female versus male faces.

    Directory of Open Access Journals (Sweden)

    Shawn N Geniole

    Full Text Available The facial width-to-height ratio (face ratio, is a sexually dimorphic metric associated with actual aggression in men and with observers' judgements of aggression in male faces. Here, we sought to determine if observers' judgements of aggression were associated with the face ratio in female faces. In three studies, participants rated photographs of female and male faces on aggression, femininity, masculinity, attractiveness, and nurturing. In Studies 1 and 2, for female and male faces, judgements of aggression were associated with the face ratio even when other cues in the face related to masculinity were controlled statistically. Nevertheless, correlations between the face ratio and judgements of aggression were smaller for female than for male faces (F(1,36 = 7.43, p = 0.01. In Study 1, there was no significant relationship between judgements of femininity and of aggression in female faces. In Study 2, the association between judgements of masculinity and aggression was weaker in female faces than for male faces in Study 1. The weaker association in female faces may be because aggression and masculinity are stereotypically male traits. Thus, in Study 3, observers rated faces on nurturing (a stereotypically female trait and on femininity. Judgements of nurturing were associated with femininity (positively and masculinity (negatively ratings in both female and male faces. In summary, the perception of aggression differs in female versus male faces. The sex difference was not simply because aggression is a gendered construct; the relationships between masculinity/femininity and nurturing were similar for male and female faces even though nurturing is also a gendered construct. Masculinity and femininity ratings are not associated with aggression ratings nor with the face ratio for female faces. In contrast, all four variables are highly inter-correlated in male faces, likely because these cues in male faces serve as "honest signals".

  9. Facing aggression: cues differ for female versus male faces.

    Science.gov (United States)

    Geniole, Shawn N; Keyes, Amanda E; Mondloch, Catherine J; Carré, Justin M; McCormick, Cheryl M

    2012-01-01

    The facial width-to-height ratio (face ratio), is a sexually dimorphic metric associated with actual aggression in men and with observers' judgements of aggression in male faces. Here, we sought to determine if observers' judgements of aggression were associated with the face ratio in female faces. In three studies, participants rated photographs of female and male faces on aggression, femininity, masculinity, attractiveness, and nurturing. In Studies 1 and 2, for female and male faces, judgements of aggression were associated with the face ratio even when other cues in the face related to masculinity were controlled statistically. Nevertheless, correlations between the face ratio and judgements of aggression were smaller for female than for male faces (F(1,36) = 7.43, p = 0.01). In Study 1, there was no significant relationship between judgements of femininity and of aggression in female faces. In Study 2, the association between judgements of masculinity and aggression was weaker in female faces than for male faces in Study 1. The weaker association in female faces may be because aggression and masculinity are stereotypically male traits. Thus, in Study 3, observers rated faces on nurturing (a stereotypically female trait) and on femininity. Judgements of nurturing were associated with femininity (positively) and masculinity (negatively) ratings in both female and male faces. In summary, the perception of aggression differs in female versus male faces. The sex difference was not simply because aggression is a gendered construct; the relationships between masculinity/femininity and nurturing were similar for male and female faces even though nurturing is also a gendered construct. Masculinity and femininity ratings are not associated with aggression ratings nor with the face ratio for female faces. In contrast, all four variables are highly inter-correlated in male faces, likely because these cues in male faces serve as "honest signals".

  10. Facing Aggression: Cues Differ for Female versus Male Faces

    Science.gov (United States)

    Geniole, Shawn N.; Keyes, Amanda E.; Mondloch, Catherine J.; Carré, Justin M.; McCormick, Cheryl M.

    2012-01-01

    The facial width-to-height ratio (face ratio), is a sexually dimorphic metric associated with actual aggression in men and with observers' judgements of aggression in male faces. Here, we sought to determine if observers' judgements of aggression were associated with the face ratio in female faces. In three studies, participants rated photographs of female and male faces on aggression, femininity, masculinity, attractiveness, and nurturing. In Studies 1 and 2, for female and male faces, judgements of aggression were associated with the face ratio even when other cues in the face related to masculinity were controlled statistically. Nevertheless, correlations between the face ratio and judgements of aggression were smaller for female than for male faces (F1,36 = 7.43, p = 0.01). In Study 1, there was no significant relationship between judgements of femininity and of aggression in female faces. In Study 2, the association between judgements of masculinity and aggression was weaker in female faces than for male faces in Study 1. The weaker association in female faces may be because aggression and masculinity are stereotypically male traits. Thus, in Study 3, observers rated faces on nurturing (a stereotypically female trait) and on femininity. Judgements of nurturing were associated with femininity (positively) and masculinity (negatively) ratings in both female and male faces. In summary, the perception of aggression differs in female versus male faces. The sex difference was not simply because aggression is a gendered construct; the relationships between masculinity/femininity and nurturing were similar for male and female faces even though nurturing is also a gendered construct. Masculinity and femininity ratings are not associated with aggression ratings nor with the face ratio for female faces. In contrast, all four variables are highly inter-correlated in male faces, likely because these cues in male faces serve as “honest signals”. PMID:22276184

  11. Aggressive behaviour in preschool children. Neuropsychological correlates, costs of service use, and preventive efforts.

    NARCIS (Netherlands)

    Raaijmakers, M.A.J.

    2008-01-01

    At ages two and three the vast majority of children shows a high level of aggression. During the preschool period the level of aggression generally declines. However, some children continue to show a high level of aggression and are at risk for the development of Disruptive Behavior Disorders (DBD),

  12. Should I Say Something? Dating and Sexual Aggression Bystander Intervention among High School Youth. National Issue Brief Number 92

    Science.gov (United States)

    Edwards, Katie M.; Eckstein, Robert P.; Rodenhizer-Stämpfli , Kara Anne

    2015-01-01

    Using data from a sample of 218 high school youth from three high schools in New England (one rural, two urban), this brief discusses dating and sexual aggression bystander intervention among high school youth. Authors Katie Edwards, Robert Eckstein, and Kara Anne Rodenhizer-Stämpfli report that an overwhelming majority (93.6 percent) of high…

  13. Normative Beliefs and Relational Aggression: An Investigation of the Cognitive Bases of Adolescent Aggressive Behavior

    Science.gov (United States)

    Werner, Nicole E.; Nixon, Charisse L.

    2005-01-01

    The relations between normative beliefs about different forms of aggression and corresponding aggressive behaviors were investigated in 2 studies of adolescents. In Study 1, we revised an instrument designed to assess normative beliefs about aggression to include beliefs about the acceptability of relational aggression, and we examined the…

  14. Prognostic significance of highly sulfated chondroitin sulfates in ovarian cancer defined by the single chain antibody GD3A11.

    Science.gov (United States)

    van der Steen, Sophieke C H A; van Tilborg, Angela A G; Vallen, Myrtille J E; Bulten, Johan; van Kuppevelt, Toin H; Massuger, Leon F A G

    2016-03-01

    The extracellular matrix (ECM) of ovarian cancer may provide a number of potential biomarkers. Chondroitin sulfate (CS), a class of sulfated polysaccharides, is abundantly present in the ECM of ovarian cancer. Structural alterations of CS chains (i.e. sulfation pattern) have been demonstrated to play a role in cancer development and progression. In this study we investigate the potential of highly sulfated CS as a biomarker in ovarian cancer using the single chain antibody GD3A11 selected by the phage display technology. The specificity of the antibody was determined by an indirect ELISA. GD3A11 epitope expression was assessed by immunohistochemistry in healthy organs, benign and malignant ovarian tumors (N=359) and correlated to clinical parameters. The CHST15 gene, responsible for the biosynthesis of highly sulfated CS was evaluated for mutation and methylation status. The GD3A11 epitope was minimally expressed in normal organs. Intense expression was observed in the ECM of different ovarian cancer subtypes, in contrast to benign ovarian tumors. Expression was independent of tumor grade, FIGO stage, and the use chemotherapy. For the aggressive ovarian cancer phenotype, intense expression was identified as an independent predictor for poor prognosis. CHST15 gene analysis showed no mutations nor an altered methylation status. Specific highly sulfated CS motifs expressed in the tumoral ECM hold biomarker potential in ovarian cancer patients. These matrix motifs constitute a novel class of biomarkers with prognostic significance and may be instrumental for innovative diagnostic and therapeutic applications (e.g. targeted therapy) in management of ovarian cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Digit Ratio (2D:4D, Aggression, and Testosterone in Men Exposed to an Aggressive Video Stimulus

    Directory of Open Access Journals (Sweden)

    Liam P. Kilduff

    2013-07-01

    Full Text Available The relative lengths of the 2nd and 4th digits (2D:4D is a negative biomarker for prenatal testosterone, and low 2D:4D may be associated with aggression. However, the evidence for a 2D:4D-aggression association is mixed. Here we test the hypothesis that 2D:4D is robustly linked to aggression in “challenge” situations in which testosterone is increased. Participants were exposed to an aggressive video and a control video. Aggression was measured after each video and salivary free testosterone levels before and after each video. Compared to the control video, the aggressive video was associated with raised aggression responses and a marginally significant increase in testosterone. Left 2D:4D was negatively correlated with aggression after the aggressive video and the strength of the correlation was higher in those participants who showed the greatest increases in testosterone. Left 2D:4D was also negatively correlated to the difference between aggression scores in the aggressive and control conditions. The control video did not influence testosterone concentrations and there were no associations between 2D:4D and aggression. We conclude that 2D:4D moderates the impact of an aggressive stimulus on aggression, such that an increase in testosterone resulting from a “challenge” is associated with a negative correlation between 2D:4D and aggression.

  16. Authoritative School Climate, Aggression toward Teachers, and Teacher Distress in Middle School

    Science.gov (United States)

    Berg, Juliette K.; Cornell, Dewey

    2016-01-01

    Aggression toward teachers is linked to burnout and disengagement from teaching, but a positive school climate may reduce aggression and associated teacher distress. Using authoritative school climate theory, the study examined whether schools with high disciplinary structure and student support were associated with less aggression and less…

  17. Perpetration of Alcohol-Related Aggression by Male and Female College Students: An Examination of Overt and Relational Aggression.

    Science.gov (United States)

    Robertson, Kirsten; Forbes, Sarah; Thyne, Maree

    2017-03-01

    Existing literature exemplifies the relationship between alcohol and overt aggression, especially for adult males. Less clear is the relationship between alcohol and aggression among male and female college students, in particular, the nature of this aggression and the co-occurrence of drinking and aggression on the same day (temporal proximity). This study examines the chronic and temporal nature of males' and females' alcohol-related aggression among college students. Two hundred fourteen students completed a web-based 7-day event-level survey measuring alcohol consumption and perpetration of physical aggression, verbal aggression, anger, and relational aggression over 4 weeks, resulting in 4,256 observations (days). The global analysis revealed students who are heavy drinkers are more likely to perpetrate all four forms of aggression, whereas the event-level analysis revealed that specific forms of aggression are associated with drinking at the time, while other forms were not linked to drinking occasions. Cross-tabulation revealed males and females were more likely to use verbal and physical aggression when drinking. For females, drinking was also associated with relational aggression and anger. Despite often being overlooked in research on aggression during emerging adulthood, relational aggression was prevalent. Discrepancies between the global and temporal analysis revealed factors other than alcohol might explain the relationship between chronic alcohol consumption and specific forms of aggression. This is one of the first event-level studies to show the temporal relationship between alcohol and relational aggression. The distinctions in the current study, exemplifying the diversity of alcohol-related aggression, are critical for understanding aggressive behavior, potential gender differences, and for developing interventions. The temporal relationship between alcohol and aggression suggests health interventions should target drinking and aggression

  18. Subjective socioeconomic status causes aggression: A test of the theory of social deprivation.

    Science.gov (United States)

    Greitemeyer, Tobias; Sagioglou, Christina

    2016-08-01

    Seven studies (overall N = 3690) addressed the relation between people's subjective socioeconomic status (SES) and their aggression levels. Based on relative deprivation theory, we proposed that people low in subjective SES would feel at a disadvantage, which in turn would elicit aggressive responses. In 3 correlational studies, subjective SES was negatively related to trait aggression. Importantly, this relation held when controlling for measures that are related to 1 or both subjective SES and trait aggression, such as the dark tetrad and the Big Five. Four experimental studies then demonstrated that participants in a low status condition were more aggressive than were participants in a high status condition. Compared with a medium-SES condition, participants of low subjective SES were more aggressive rather than participants of high subjective SES being less aggressive. Moreover, low SES increased aggressive behavior toward targets that were the source for participants' experience of disadvantage but also toward neutral targets. Sequential mediation analyses suggest that the experience of disadvantage underlies the effect of subjective SES on aggressive affect, whereas aggressive affect was the proximal determinant of aggressive behavior. Taken together, the present research found comprehensive support for key predictions derived from the theory of relative deprivation of how the perception of low SES is related to the person's judgments, emotional reactions, and actions. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  19. Prognostic Biomarkers Used for Localised Prostate Cancer Management: A Systematic Review.

    Science.gov (United States)

    Lamy, Pierre-Jean; Allory, Yves; Gauchez, Anne-Sophie; Asselain, Bernard; Beuzeboc, Philippe; de Cremoux, Patricia; Fontugne, Jacqueline; Georges, Agnès; Hennequin, Christophe; Lehmann-Che, Jacqueline; Massard, Christophe; Millet, Ingrid; Murez, Thibaut; Schlageter, Marie-Hélène; Rouvière, Olivier; Kassab-Chahmi, Diana; Rozet, François; Descotes, Jean-Luc; Rébillard, Xavier

    2017-03-07

    Prostate cancer stratification is based on tumour size, pretreatment PSA level, and Gleason score, but it remains imperfect. Current research focuses on the discovery and validation of novel prognostic biomarkers to improve the identification of patients at risk of aggressive cancer or of tumour relapse. This systematic review by the Intergroupe Coopérateur Francophone de Recherche en Onco-urologie (ICFuro) analysed new evidence on the analytical validity and clinical validity and utility of six prognostic biomarkers (PHI, 4Kscore, MiPS, GPS, Prolaris, Decipher). All available data for the six biomarkers published between January 2002 and April 2015 were systematically searched and reviewed. The main endpoints were aggressive prostate cancer prediction, additional value compared to classical prognostic parameters, and clinical benefit for patients with localised prostate cancer. The preanalytical and analytical validations were heterogeneous for all tests and often not adequate for the molecular signatures. Each biomarker was studied for specific indications (candidates for a first or second biopsy, and potential candidates for active surveillance, radical prostatectomy, or adjuvant treatment) for which the level of evidence (LOE) was variable. PHI and 4Kscore were the biomarkers with the highest LOE for discriminating aggressive and indolent tumours in different indications. Blood biomarkers (PHI and 4Kscore) have the highest LOE for the prediction of more aggressive prostate cancer and could help clinicians to manage patients with localised prostate cancer. The other biomarkers show a potential prognostic value; however, they should be evaluated in additional studies to confirm their clinical validity. We reviewed studies assessing the value of six prognostic biomarkers for prostate cancer. On the basis of the available evidence, some biomarkers could help in discriminating between aggressive and non-aggressive tumours with an additional value compared to the

  20. Oscillatory brain activity related to control mechanisms during laboratory-induced reactive aggression

    Directory of Open Access Journals (Sweden)

    Ulrike M Krämer

    2009-11-01

    Full Text Available Aggressive behavior is a common reaction in humans after an interpersonal provocation, but little is known about the underlying brain mechanisms. The present study analyzed oscillatory brain activity while participants were involved in an aggressive interaction to examine the neural processes subserving the associated decision and evaluation processes. Participants were selected from a larger sample because of their high scores in trait aggressiveness. We used a competitive reaction time task that induces aggressive behavior through provocation. Each trial is separated in a decision phase, during which the punishment for the opponent is set, and an outcome phase, during which the actual punishment is applied or received. We observed provocation-related differences during the decision phase in the theta band which differed depending on participants’ aggressive behavior: High provocation was associated with an increased frontal theta response in participants refraining from retaliation, but with reduced theta power in those who got back to the opponent. Moreover, more aggressive decisions after being punished were associated with a decrease of frontal theta power. Non-aggressive and aggressive participants differed also in their outcome-related response: Being punished led to an increased frontal theta power compared to win trials in the latter only, pointing to differences in evaluation processes associated with their different behavioral reactions. The data thus support previous evidence for a role of prefrontal areas in the control of reactive aggression and extend behavioral studies on associations between aggression or violence and impaired prefrontal functions.

  1. Threatening Men's Mate Value Influences Aggression Toward an Intrasexual Rival: The Moderating Role of Narcissism.

    Science.gov (United States)

    Bird, Brian M; Carré, Justin M; Knack, Jennifer M; Arnocky, Steven

    2016-01-01

    Correlational research has linked low mate value (MV)--one's worth as a mating partner to members of the opposite sex--with aggression in men. In 2 experiments, we examined the effects of self-perceived MV on men's reported willingness to aggress directly toward a hypothetical mate poacher (Experiment 1, N = 60) and observable aggression toward a same-sex rival in a laboratory paradigm (Experiment 2, N = 54). In both experiments, the roles of narcissism in moderating the effect of MV condition on subsequent aggression were examined. Results of Experiment 1 indicated that men randomly assigned to the low MV condition were significantly more willing to report aggressive intention than men in the high MV condition. This relationship was moderated by narcissism such that men in the low MV condition who were also high in narcissism were the most likely to aggress. Results of Experiment 2 similarly showed that men in the low MV condition relative to the high MV condition aggressed more toward a same-sex rival when they were high in narcissism. These findings support evolutionary hypotheses surrounding the importance of self-perceived MV in directing aggressive mating efforts, as situated in the framework of threatened egotism.

  2. Angio-Architectural Features of High-Grade Intracranial Dural Arteriovenous Fistulas: Correlation With Aggressive Clinical Presentation and Hemorrhagic Risk.

    Science.gov (United States)

    Della Pepa, Giuseppe Maria; Parente, Paolo; D'Argento, Francesco; Pedicelli, Alessandro; Sturiale, Carmelo Lucio; Sabatino, Giovanni; Albanese, Alessio; Puca, Alfredo; Fernandez, Eduardo; Olivi, Alessando; Marchese, Enrico

    2017-08-01

    High-grade dural arteriovenous fistulas (dAVFs) can present shunts with very different angio-architectural characteristics. Specific hemodynamic factors may affect clinical history and determine very different clinical courses. To evaluate the relationship between some venous angio-architectural features in high-grade dAVFs and clinical presentation. Specific indicators of moderate or severe venous hypertension were analyzed, such as altered configurations of the dural sinuses (by a single or a dual thrombosis), or overload of cortical vessels (restrictions of outflow, pseudophlebitic cortical vessels, and venous aneurysms). The institutional series was retrospectively reviewed (49 cases), and the pattern of venous drainage was analyzed in relationship with clinical presentation (benign/aggressive/hemorrhage). Thirty-five of 49 cases displayed cortical reflux (high-grade dAVFs). This subgroup displayed a benign presentation in 31.42% of cases, an aggressive in 31.42%, and hemorrhage in 37.14%. Our data confirm that within high-grade dAVFs, 2 distinct subpopulations exist according to severity of clinical presentation. Some indicators we examined showed correlation with aggressive nonhemorrhagic manifestations (outflow restriction and pseudophlebitic cortical vessels), while other showed a correlation with hemorrhage (dual thrombosis and venous aneurysms). Current classifications appear insufficient to identify a wide range of conditions that ultimately determine the organization of the cortical venous drainage. Intermediate degrees of venous congestion correlate better with the clinical risk than the simple definition of cortical reflux. The angiographic aspects of venous drainage presented in this study may prove useful to assess dAVF hemodynamic characteristics and identify conditions at higher clinical risk. Copyright © 2017 by the Congress of Neurological Surgeons

  3. Trait correlates of relational aggression in a nonclinical sample: DSM-IV personality disorders and psychopathy.

    Science.gov (United States)

    Schmeelk, Kelly M; Sylvers, Patrick; Lilienfeld, Scott O

    2008-06-01

    The implications of adult relational aggression in adults for personality pathology are poorly understood. We investigated the association between relational aggression and features of DSM-IV personality disorders and psychopathy in a sample of undergraduates (N = 220). In contrast to the childhood literature, we found no significant difference in relational aggression between men and women. Unlike overt aggression, which correlated about equally highly with features of all three personality disorder clusters, relational aggression correlated significantly more highly with features of Cluster B than Clusters A or C. In addition, even after controlling for overt aggression, relational aggression correlated significantly with features of psychopathy, although only with Factor 2 traits. With the exception of sadistic personality disorder features, gender did not moderate the relationship between relational aggression and personality pathology. Further research on the psycho-pathological implications of relational aggression in more severely affected samples is warranted.

  4. Beyond the Positive Reinforcement of Aggression: Peers' Acceptance of Aggression Promotes Aggression via External Control Beliefs

    Science.gov (United States)

    Jung, Janis; Krahé, Barbara; Busching, Robert

    2018-01-01

    Being surrounded by peers who are accepting of aggression is a significant predictor of the development and persistence of aggression in childhood and adolescence. Whereas past research has focused on social reinforcement mechanisms as the underlying processes, the present longitudinal study analysed the role of external control beliefs as an…

  5. Oxytocin and Aggression.

    Science.gov (United States)

    de Jong, Trynke R; Neumann, Inga D

    2017-09-02

    The neuropeptide oxytocin (OT) has a solid reputation as a facilitator of social interactions such as parental and pair bonding, trust, and empathy. The many results supporting a pro-social role of OT have generated the hypothesis that impairments in the endogenous OT system may lead to antisocial behavior, most notably social withdrawal or pathological aggression. If this is indeed the case, administration of exogenous OT could be the "serenic" treatment that psychiatrists have for decades been searching for.In the present review, we list and discuss the evidence for an endogenous "hypo-oxytocinergic state" underlying aggressive and antisocial behavior, derived from both animal and human studies. We furthermore examine the reported effects of synthetic OT administration on aggression in rodents and humans.Although the scientific findings listed in this review support, in broad lines, the link between a down-regulated or impaired OT system activity and increased aggression, the anti-aggressive effects of synthetic OT are less straightforward and require further research. The rather complex picture that emerges adds to the ongoing debate questioning the unidirectional pro-social role of OT, as well as the strength of the effects of intranasal OT administration in humans.

  6. Children's exposure to violent political conflict stimulates aggression at peers by increasing emotional distress, aggressive script rehearsal, and normative beliefs favoring aggression.

    Science.gov (United States)

    Huesmann, L Rowell; Dubow, Eric F; Boxer, Paul; Landau, Simha F; Gvirsman, Shira Dvir; Shikaki, Khalil

    2017-02-01

    We examine the hypothesis that children's exposure to ethnic-political conflict and violence over the course of a year stimulates their increased aggression toward their own in-group peers in subsequent years. In addition, we examine what social cognitive and emotional processes mediate these effects and how these effects are moderated by gender, age, and ethnic group. To accomplish these aims, we collected three waves of data from 901 Israeli and 600 Palestinian youths (three age cohorts: 8, 11, and 14 years old) and their parents at 1-year intervals. Exposure to ethnic-political violence was correlated with aggression at in-group peers among all age cohorts. Using a cross-lagged structural equation model from Year 1 to Year 3, we found that the relation between exposure and aggression is more plausibly due to exposure to ethnic-political violence stimulating later aggression at peers than vice versa, and this effect was not moderated significantly by gender, age cohort, or ethnic group. Using three-wave structural equation models, we then showed that this effect was significantly mediated by changes in normative beliefs about aggression, aggressive script rehearsal, and emotional distress produced by the exposure. Again the best fitting model did not allow for moderation by gender, age cohort, or ethnic group. The findings are consistent with recent theorizing that exposure to violence leads to changes both in emotional processes promoting aggression and in the acquisition through observational learning of social cognitions promoting aggression.

  7. A concept analysis of relational aggression.

    Science.gov (United States)

    Gomes, M M

    2007-08-01

    The purpose of this article is to conduct a concept analysis of the phenomenon of relational aggression. With the increases in violence among our youth, the topic of aggression, and more specifically relational aggression, has gained an increasing interest. Discussion of relational aggression is imperative because it lends credence to a type of aggression not readily studied in previous decades. A new understanding of relational aggression will aide in future nursing and multidisciplinary research studies and will guide health promotion interventions to alleviate the consequences of relational aggression for adolescent girls. Therefore, with an increased knowledge about the consequences of relational aggression the nurse can provide appropriate nursing interventions to combat the detriment associated with it.

  8. Comparative Analysis of Personality Structures of the Perpetrators of Aggressive and Non-aggressive Offense

    Directory of Open Access Journals (Sweden)

    Kalashnikova A.S.,

    2014-11-01

    Full Text Available problem of the emergence of aggressive behavior is seen through the analysis of the relationship of proagressive and inhibiting aggression personality structures. The study involved 54 men serving sentences for criminal offenses, of which 24 were accused for violent offenses and 30 - for offenses without resorting to violence. We used questionnaires to study the proagressive and deterring aggression personality structures. Statistical analysis was performed to reveal significant differences between groups and to determine correlations. On this basis, the correlations were interpreted with the help of not only quantitative but also qualitative analysis. The results showed no significant differences in the level of expression of aggression and aggression inhibitors between treatment groups, but we identified qualitative differences in the structural analysis of data from individual psychological characteristics that are expected to distinguish aggressive offenders from the perpetrators without violence.

  9. Ares and Babbitt in the classroom: effects of competition and reward on children's aggression.

    Science.gov (United States)

    Rocha, R F; Rogers, R W

    1976-05-01

    In many competitive situations, aggression is one of several instrumental behaviors that can produce reinforcing consequences. Despite the fact that aggression precipitated by competition for valued resources is an increasingly important social problem, there is little evidence of a causal relationship. In a factorial experiment, dyads of 64 kindergarten and first-grade males played a game in a face-to-face setting that yielded a prize for the winner only. It was predicted that high levels of competition and high levels of reward magnitude would produce more aggressive behavior than lower levels of these variables. Additionally, children rated by their teachers as high in dispositional aggressiveness were anticipated to behave most aggressively in the game. Each of these predictions was confirmed on three different measures of aggression: verbal, interference, and physical. Furthermore, the data suggested that constructive action was sometimes abandoned in attempts to harm an opponent. Since competition for desirable objects is a social reality, it was concluded that conditions inhibiting aggression in these situations should be investigated.

  10. Differentiation between malignant and benign thyroid nodules and stratification of papillary thyroid cancer with aggressive histological features: Whole-lesion diffusion-weighted imaging histogram analysis.

    Science.gov (United States)

    Hao, Yonghong; Pan, Chu; Chen, WeiWei; Li, Tao; Zhu, WenZhen; Qi, JianPin

    2016-12-01

    To explore the usefulness of whole-lesion histogram analysis of apparent diffusion coefficient (ADC) derived from reduced field-of-view (r-FOV) diffusion-weighted imaging (DWI) in differentiating malignant and benign thyroid nodules and stratifying papillary thyroid cancer (PTC) with aggressive histological features. This Institutional Review Board-approved, retrospective study included 93 patients with 101 pathologically proven thyroid nodules. All patients underwent preoperative r-FOV DWI at 3T. The whole-lesion ADC assessments were performed for each patient. Histogram-derived ADC parameters between different subgroups (pathologic type, extrathyroidal extension, lymph node metastasis) were compared. Receiver operating characteristic curve analysis was used to determine optimal histogram parameters in differentiating benign and malignant nodules and predicting aggressiveness of PTC. Mean ADC, median ADC, 5 th percentile ADC, 25 th percentile ADC, 75 th percentile ADC, 95 th percentile ADC (all P histogram analysis might help to differentiate malignant nodules from benign ones and show the PTCs with extrathyroidal extension. J. Magn. Reson. Imaging 2016;44:1546-1555. © 2016 International Society for Magnetic Resonance in Medicine.

  11. Anger under control: neural correlates of frustration as a function of trait aggression.

    Directory of Open Access Journals (Sweden)

    Christina M Pawliczek

    Full Text Available Antisocial behavior and aggression are prominent symptoms in several psychiatric disorders including antisocial personality disorder. An established precursor to aggression is a frustrating event, which can elicit anger or exasperation, thereby prompting aggressive responses. While some studies have investigated the neural correlates of frustration and aggression, examination of their relation to trait aggression in healthy populations are rare. Based on a screening of 550 males, we formed two extreme groups, one including individuals reporting high (n=21 and one reporting low (n=18 trait aggression. Using functional magnetic resonance imaging (fMRI at 3T, all participants were put through a frustration task comprising unsolvable anagrams of German nouns. Despite similar behavioral performance, males with high trait aggression reported higher ratings of negative affect and anger after the frustration task. Moreover, they showed relatively decreased activation in the frontal brain regions and the dorsal anterior cingulate cortex (dACC as well as relatively less amygdala activation in response to frustration. Our findings indicate distinct frontal and limbic processing mechanisms following frustration modulated by trait aggression. In response to a frustrating event, HA individuals show some of the personality characteristics and neural processing patterns observed in abnormally aggressive populations. Highlighting the impact of aggressive traits on the behavioral and neural responses to frustration in non-psychiatric extreme groups can facilitate further characterization of neural dysfunctions underlying psychiatric disorders that involve abnormal frustration processing and aggression.

  12. Aggression in adolescents: characteristics and treatment.

    Science.gov (United States)

    Ristić-Dimitrijević, Radmila; Lazić, Dijana; Nenadović, Milutin; Djokić-Pjescić, Katarina; Klidonas, Nikolaos; Stefanović, Vesna

    2011-12-01

    Vulnerability of young people and frustration of their basic biological, emotional, cognitive and social needs can induce a series of psycho-pathological manifestations, including aggression. Aim of this study is to examine the manifestations of aggressiveness in young people and to establish the difference between aggressive responses of two age groups; adolescents aged 16-19 years and older adolescents aged 20-26 years. The sample consists of 100 young people aged 16-19 years (46 adolescents) and 20-26 years (54 adolescents). For the purposes of this study, we have constructed a questionnaire in which we entered the data obtained on the basis of a standard psychiatric examination, auto- and hetero-anamnesis data, and data obtained using the standard battery of psychological tests. Statistically significant association was found between verbal aggression and physical aggression (p = 0.002), verbal aggression and suicide attempts (p = 0.02), verbal aggression and substance abuse (p = 0.009), verbal aggression and low frustration tolerance (LFT) (p = 0.007), suicide attempt and LFT (p = 0.052). The younger group was significantly more verbally aggressive compared to the older group (p = 0.01). Verbal aggression, which was significantly associated with physical aggression, suicide attempts, substance abuse and LFT, indicates the need for timely interventions for the prevention of more serious and malignant forms of aggression.

  13. Relational aggression and marital quality: A five-year longitudinal study.

    Science.gov (United States)

    Coyne, Sarah M; Nelson, David A; Carroll, Jason S; Smith, Nathan J; Yang, Chongming; Holmgren, Hailey G; Johnson, Chad

    2017-04-01

    Relational aggression occurs in many different contexts, including in romantic relationships. The current study examined associations between two subtypes of relational aggression (love withdrawal and social sabotage) and marital quality over a 5-year time period. Participants consisted of 311 married couples who completed a number of questionnaires on relational aggression and relationship quality once a year over a 5-year period. Results revealed that relational aggression was highly stable over time and that women used more relational aggression than men. Men's use of social sabotage and love withdrawal were bidirectionally related to both partners' perceptions of poor marital quality over time. Conversely, only women's use of love withdrawal was related to her own perceptions of poor marital quality over time. Collectively, these results suggest that relational aggression by men may be less common, though particularly toxic in a marital relationship. Couples are encouraged to find healthier ways of coping with problems in relationships. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  14. New Developments in Breast Cancer Screening and Treatment.

    Science.gov (United States)

    Tilstra, Sarah; McNeil, Melissa

    2017-01-01

    The clinical update serves as a brief review of recently published, high-impact, and potentially practice-changing journal articles summarized for our readers. In this clinical update, we selected top recent articles regarding breast health that may change the clinical practice of women's health providers. We identified articles by reviewing high-impact medical and women's health journals as well as national practice guidelines. Three of our articles are dedicated to the rapid changes in breast cancer screening. With regard to breast cancer treatment, we focused on two articles that impact who we treat with traditional aggressive regimens.

  15. Policy Implications of Present Knowledge on the Development and Prevention of Physical Aggression

    NARCIS (Netherlands)

    Junger, Marianne; Feder, Lynette; Cote, Sylvana M.

    2007-01-01

    Research indicates that children are born with aggressive tendencies which they learn to control through early socialization. A small group, however, shows high aggression levels early on which remain stable throughout their life. Physical aggression is an epiphenomenon in a wide variety of

  16. Behavioural strategies of aggressive and non-aggressive male mice in response to inescapable shock

    NARCIS (Netherlands)

    Benus, R.F.; Bohus, B.; Koolhaas, J.M.; Oortmerssen, G.A. van

    1990-01-01

    The effect of exposure to inescapable long-duration shocks of moderate intensity on intershock activity and on subsequent escape or avoidance performance was studied in aggressive and non-aggressive male mice. The activity of the non-aggressive mice was severely suppressed during the inescapable

  17. Mouse Models of Gastric Cancer

    Science.gov (United States)

    Hayakawa, Yoku; Fox, James G.; Gonda, Tamas; Worthley, Daniel L.; Muthupalani, Sureshkumar; Wang, Timothy C.

    2013-01-01

    Animal models have greatly enriched our understanding of the molecular mechanisms of numerous types of cancers. Gastric cancer is one of the most common cancers worldwide, with a poor prognosis and high incidence of drug-resistance. However, most inbred strains of mice have proven resistant to gastric carcinogenesis. To establish useful models which mimic human gastric cancer phenotypes, investigators have utilized animals infected with Helicobacter species and treated with carcinogens. In addition, by exploiting genetic engineering, a variety of transgenic and knockout mouse models of gastric cancer have emerged, such as INS-GAS mice and TFF1 knockout mice. Investigators have used the combination of carcinogens and gene alteration to accelerate gastric cancer development, but rarely do mouse models show an aggressive and metastatic gastric cancer phenotype that could be relevant to preclinical studies, which may require more specific targeting of gastric progenitor cells. Here, we review current gastric carcinogenesis mouse models and provide our future perspectives on this field. PMID:24216700

  18. Nuclear Kaiso expression is associated with high grade and triple-negative invasive breast cancer.

    Directory of Open Access Journals (Sweden)

    Jeroen F Vermeulen

    Full Text Available Kaiso is a BTB/POZ transcription factor that is ubiquitously expressed in multiple cell types and functions as a transcriptional repressor and activator. Little is known about Kaiso expression and localization in breast cancer. Here, we have related pathological features and molecular subtypes to Kaiso expression in 477 cases of human invasive breast cancer. Nuclear Kaiso was predominantly found in invasive ductal carcinoma (IDC (p = 0.007, while cytoplasmic Kaiso expression was linked to invasive lobular carcinoma (ILC (p = 0.006. Although cytoplasmic Kaiso did not correlate to clinicopathological features, we found a significant correlation between nuclear Kaiso, high histological grade (p = 0.023, ERα negativity (p = 0.001, and the HER2-driven and basal/triple-negative breast cancers (p = 0.018. Interestingly, nuclear Kaiso was also abundant in BRCA1-associated breast cancer (p<0.001 and invasive breast cancer overexpressing EGFR (p = 0.019. We observed a correlation between nuclear Kaiso and membrane-localized E-cadherin and p120-catenin (p120 (p<0.01. In contrast, cytoplasmic p120 strongly correlated with loss of E-cadherin and low nuclear Kaiso (p = 0.005. We could confirm these findings in human ILC cells and cell lines derived from conditional mouse models of ILC. Moreover, we present functional data that substantiate a mechanism whereby E-cadherin controls p120-mediated relief of Kaiso-dependent gene repression. In conclusion, our data indicate that nuclear Kaiso is common in clinically aggressive ductal breast cancer, while cytoplasmic Kaiso and a p120-mediated relief of Kaiso-dependent transcriptional repression characterize ILC.

  19. Outcomes of aggressive treatment in esophageal cancer patients with synchronous solitary brain metastasis.

    Science.gov (United States)

    Onal, Cem; Akkus Yildirim, Berna; Guler, Ozan Cem

    2017-07-01

    The aim of the present study was to investigate the outcomes of esophageal cancer (EC) patients with isolated synchronous brain oligometastasis (oligo-BM) treated with chemoradiotherapy (CRT) of the primary site and localized treatment of the BM with surgery, radiotherapy (RT) or radiosurgery. Of 125 EC patients investigated, seven patients (6%) had solitary BM. Six patients were diagnosed prior to, and one patient was diagnosed during, treatment. All patients were treated with neoadjuvant chemotherapy and whole-brain RT (WBRT) for BM. All but one patient received definitive CRT with a median RT dose of 50.4 Gy using conventional fractionation RT. The median age at diagnosis was 59 years (range, 48-77 years). Six patients succumbed to mortality, and one continued to receive systemic chemotherapy at the last visit. The median survival time of the patients was 18.9 months (range, 10.0-27.2 months). Median time to progression after completion of the treatments was 8 months (range, 3-9 months). Two patients had progression of the primary tumor, and one patient had progression of the BM. The neurological status of three patients with BM who were identified during the staging work-up did not deteriorate as a consequence of WBRT. In conclusion, the present study has demonstrated that aggressive treatment of the primary tumor and oligo-BM in patients with EC may prolong the survival time.

  20. Pleomorphic lobular carcinoma: is it more similar to a classic lobular cancer or to a high-grade ductal cancer?

    Directory of Open Access Journals (Sweden)

    Costarelli L

    2017-12-01

    Full Text Available Leopoldo Costarelli, Domenico Campagna, Alessandra Ascarelli, Francesco Cavaliere, Maria Helena Colavito, Tatiana Ponzani, Laura Broglia, Massimo La Pinta, Elena Manna, Lucio Fortunato Breast Unit, San Giovanni-Addolorata Hospital, Rome, Italy Background: Pleomorphic invasive lobular carcinoma (P-ILC is an uncommon variety of invasive lobular carcinoma with aggressive clinical features. Little is described in the literature regarding this topic.Materials and methods: We reviewed our experiences from 2010 to 2015 and compared 40 patients with P-ILC, 126 patients with classic-ILC (C-ILC and 574 cases of high-grade invasive ductal carcinoma (HG-IDC. We studied the histologic and immunohistochemical features, clinical presentation and surgical treatment.Results: P-ILC is diagnosed at the same age and tumor diameter as those of the other two histologic types. It is associated more frequently with multiple lymph node metastases and high proliferative index, and HER2/neu is amplified in 10% of cases. In spite of sharing some histologic characteristics with C-ILC (same growth pattern, loss of E-cadherin expression, same genetic pathway, its clinical and pathologic features define an autonomous entity. Its surgical treatment is similar to those of C-ILC and HG-IDC.Conclusion: This is the first review comparing these three pathologic entities. Our findings may be useful in understanding this variety of invasive lobular carcinoma, and further studies are certainly needed in this field. Keywords: breast cancer, lobular cancer, pleomorphic, mastectomy

  1. The Prognostic Nutritional Index Predicts Survival and Identifies Aggressiveness of Gastric Cancer.

    Science.gov (United States)

    Eo, Wan Kyu; Chang, Hye Jung; Suh, Jungho; Ahn, Jin; Shin, Jeong; Hur, Joon-Young; Kim, Gou Young; Lee, Sookyung; Park, Sora; Lee, Sanghun

    2015-01-01

    Nutritional status has been associated with long-term outcomes in cancer patients. The prognostic nutritional index (PNI) is calculated by serum albumin concentration and absolute lymphocyte count, and it may be a surrogate biomarker for nutritional status and possibly predicts overall survival (OS) of gastric cancer. We evaluated the value of the PNI as a predictor for disease-free survival (DFS) in addition to OS in a cohort of 314 gastric cancer patients who underwent curative surgical resection. There were 77 patients in PNI-low group (PNI ≤ 47.3) and 237 patients in PNI-high group (PNI > 47.3). With a median follow-up of 36.5 mo, 5-yr DFS rates in PNI-low group and PNI-high group were 63.5% and 83.6% and 5-yr OS rates in PNI-low group and PNI-high group were 63.5% and 88.4%, respectively (DFS, P < 0.0001; OS, P < 0.0001). In the multivariate analysis, the only predictors for DFS were PNI, tumor-node-metastasis (TNM) stage, and perineural invasion, whereas the only predictors for OS were PNI, age, TNM stage, and perineural invasion. In addition, the PNI was independent of various inflammatory markers. In conclusion, the PNI is an independent prognostic factor for both DFS and OS, and provides additional prognostic information beyond pathologic parameters.

  2. Pathogenicity of the highly leukotoxic JP2 clone of Aggregatibacter actinomycetemcomitans and its geographic dissemination and role in aggressive periodontitis

    Directory of Open Access Journals (Sweden)

    Dorte Haubek

    2014-08-01

    Full Text Available For decades, Aggregatibacter actinomycetemcomitans has been associated with aggressive forms of periodontitis in adolescents. In the middle of the 1990s, a specific JP2 clone of A. actinomycetemcomitans, belonging to the cluster of serotype b strains of A. actinomycetemcomitans and having a number of other characteristics, was found to be strongly associated with aggressive forms of periodontitis, particularly in North Africa. Although several longitudinal studies still point to the bacterial species, A. actinomycetemcomitans as a risk factor of aggressive periodontitis, it is now also widely accepted that the highly leukotoxic JP2 clone of A. actinomycetemcomitans is implicated in rapidly progressing forms of aggressive periodontitis. The JP2 clone strains are highly prevalent in human populations living in Northern and Western parts of Africa. These strains are also prevalent in geographically widespread populations that have originated from the Northwest Africa. Only sporadic signs of a dissemination of the JP2 clone strains to non-African populations have been found despite Africans living geographically widespread for hundreds of years. It remains an unanswered question if a particular host tropism exists as a possible explanation for the frequent colonization of the Northwest African population with the JP2 clone. Two exotoxins of A. actinomycetemcomitans are known, leukotoxin (LtxA and cytolethal distending toxin (Cdt. LtxA is able to kill human immune cells, and Cdt can block cell cycle progression in eukaryotic cells and thus induce cell cycle arrest. Whereas the leukotoxin production is enhanced in JP2 clone strains thus increasing the virulence potential of A. actinomycetemcomitans, it has not been possible so far to demonstrate such a role for Cdt. Lines of evidence have led to the understanding of the highly leukotoxic JP2 clone of A. actinomycetemcomitans as an aetiological factor of aggressive periodontitis. Patients, who are

  3. Pathogenicity of the highly leukotoxic JP2 clone of Aggregatibacter actinomycetemcomitans and its geographic dissemination and role in aggressive periodontitis

    Science.gov (United States)

    Haubek, Dorte; Johansson, Anders

    2014-01-01

    For decades, Aggregatibacter actinomycetemcomitans has been associated with aggressive forms of periodontitis in adolescents. In the middle of the 1990s, a specific JP2 clone of A. actinomycetemcomitans, belonging to the cluster of serotype b strains of A. actinomycetemcomitans and having a number of other characteristics, was found to be strongly associated with aggressive forms of periodontitis, particularly in North Africa. Although several longitudinal studies still point to the bacterial species, A. actinomycetemcomitans as a risk factor of aggressive periodontitis, it is now also widely accepted that the highly leukotoxic JP2 clone of A. actinomycetemcomitans is implicated in rapidly progressing forms of aggressive periodontitis. The JP2 clone strains are highly prevalent in human populations living in Northern and Western parts of Africa. These strains are also prevalent in geographically widespread populations that have originated from the Northwest Africa. Only sporadic signs of a dissemination of the JP2 clone strains to non-African populations have been found despite Africans living geographically widespread for hundreds of years. It remains an unanswered question if a particular host tropism exists as a possible explanation for the frequent colonization of the Northwest African population with the JP2 clone. Two exotoxins of A. actinomycetemcomitans are known, leukotoxin (LtxA) and cytolethal distending toxin (Cdt). LtxA is able to kill human immune cells, and Cdt can block cell cycle progression in eukaryotic cells and thus induce cell cycle arrest. Whereas the leukotoxin production is enhanced in JP2 clone strains thus increasing the virulence potential of A. actinomycetemcomitans, it has not been possible so far to demonstrate such a role for Cdt. Lines of evidence have led to the understanding of the highly leukotoxic JP2 clone of A. actinomycetemcomitans as an aetiological factor of aggressive periodontitis. Patients, who are colonized with the JP2

  4. Contribution of an alveolar cell of origin to the aggressive phenotype of pregnancy-associated breast cancer

    Science.gov (United States)

    Haricharan, Svasti; Hein, Sarah; Dong, Jie; Toneff, Michael; Aina, Olulana; Rao, Pulivarthi H.; Cardiff, Robert; Li, Yi

    2014-01-01

    Pregnancy-associated breast cancers (PABCs) are malignancies diagnosed during pregnancy or up to five years following parturition, and are usually aggressive, stroma-rich, and estrogen receptor/progesterone receptor-negative; but little is known about the cellular origin of PABCs or the mechanisms by which PABCs initiate. Using the RCAS retrovirus to deliver the ErbB2 oncogene into the mammary epithelium of our previous reported MMTV-tva transgenic mice, we detected human PABC-like tumors during pregnancy and lactation but not in involuted mice or in age-matched virgin mice. More importantly, by generating a WAP-tva transgenic line for expression of ErbB2 selectively in WAP+ mammary alveolar cells, we found that the resulting tumors exhibited the hallmarks of PABCs irrespective of the time since pregnancy and even in the absence of pregnancy. These data suggest that PABCs arise preferentially from an alveolar cell population that expands during pregnancy and lactation. This somatic mouse model may also be useful for preclinical testing of new prophylactic and therapeutic strategies against PABC. PMID:24317513

  5. Genetics of aggression.

    Science.gov (United States)

    Anholt, Robert R H; Mackay, Trudy F C

    2012-01-01

    Aggression mediates competition for food, mating partners, and habitats and, among social animals, establishes stable dominance hierarchies. In humans, abnormal aggression is a hallmark of neuropsychiatric disorders and can be elicited by environmental factors acting on an underlying genetic susceptibility. Identifying the genetic architecture that predisposes to aggressive behavior in people is challenging because of difficulties in quantifying the phenotype, genetic heterogeneity, and uncontrolled environmental conditions. Studies on mice have identified single-gene mutations that result in hyperaggression, contingent on genetic background. These studies can be complemented by systems genetics approaches in Drosophila melanogaster, in which mutational analyses together with genome-wide transcript analyses, artificial selection studies, and genome-wide analysis of epistasis have revealed that a large segment of the genome contributes to the manifestation of aggressive behavior with widespread epistatic interactions. Comparative genomic analyses based on the principle of evolutionary conservation are needed to enable a complete dissection of the neurogenetic underpinnings of this universal fitness trait.

  6. Combatting workplace aggression in detainee transport: A Dutch case study

    NARCIS (Netherlands)

    Lasthuizen, K.M.; Paanakker, H.L.

    2016-01-01

    Purpose – In Dutch detainee care custodial transport police officers experience high levels of aggression and violence from detainees. Being a first of its kind in the Netherlands, the purpose of this paper is to unravel the true nature and origins of such workplace aggression against transport

  7. The relationship between personality disorder traits and reactive versus proactive motivation for aggression

    NARCIS (Netherlands)

    Lobbestael, J.; Cima, M.; Lemmens, A.

    2015-01-01

    There is a strong link between personality disorders (PDs) and aggression. This is reflected in high prevalence rates of PD diagnoses in forensic samples, and in several diagnostic criteria of PDs directly referring to elevated levels of aggression. Aggression can stem from two distinct types of

  8. Long-term efficacy and late complications after chemo- and radiotherapy in aggressive non-Hodgkin's lymphoma

    NARCIS (Netherlands)

    Moser, Elisabeth Charlotte

    2007-01-01

    For decades lymphoma patients are, whenever possible, treated in clinical trials. This thesis is based on 30 years experience of large clinical trials by the EORTC (European Organization for Research and Treatment of Cancer) Lymphoma Group in aggressive non-Hodgkin’s lymphoma (NHL). The consistent

  9. [Motives and interpersonal functions of aggression].

    Science.gov (United States)

    Ohbuchi, K

    1987-06-01

    In this review, the author theoretically and empirically examined motives and interpersonal functions of aggression. A factor-analysis of Averill's questionnaire items on anger revealed that motives involved in aggressive responses were clustered into two groups: the hostile and the instrumental. It was also clarified that an individual is likely to engage in aggression particularly when some hostile motives are evoked. Concerning the interpersonal functions, the author proposed that aggression might serve four principal goals. (1) Aggression can be generated as an avoidance response to an aversive stimulus, such as frustration, annoyance, or pain, and so on. It depends on the severity of the stimulus. It was however emphasized that aggression is also mediated by social cognition, such as an attribution of intent to a harm-doer. (2) Aggression can be used as a means of coercing the other person into doing something. An individual is likely to use such a power strategy if he/she is lacking in self-confidence or a perspective for influencing the target person by more peaceful strategies. (3) Aggression can be interpreted as a punishment when it is directed toward a transgressor. In this case, aggression is motivated by restoration of a social justice, and thus its intensity is determined by the perceived moral responsibility of the transgressor. Further, it was indicated that aggression is intensified if it is justified as a sanctional conduct against the immoral. (4) Aggression can be also evoked when an individual's social identity is threatened. It was suggested that impression management motives are involved in aggression by an unexpected finding that the presence of audience or the identifiability rather facilitated retaliative aggression. The aggression-inhibition effect of apology was also explained in terms of impression management. In conclusion, it was presented that aggression is a behavioral strategy as an attempt to resolve interpersonal conflicts

  10. Maternal Social Coaching Quality Interrupts the Development of Relational Aggression During Early Childhood.

    Science.gov (United States)

    Werner, Nicole E; Eaton, Ashley D; Lyle, Kelsey; Tseng, Heidi; Holst, Brooke

    2014-08-01

    Previous research has shown that parents of socially competent young children provide them with elaborative, explicit, appropriate and emotion-laden advice about peer interactions. The current study analyzed mothers' conversations with preschoolers (N=175; 52% female; M age = 52 months, SD = 7 months) about peer conflicts involving relational aggression. Conversations were coded for maternal elaboration, emotion references, and discussion of norm violations. Information about relational and physical aggression was collected from teachers at two assessments approximately 12 months apart for a subsample of 136 children. Regression analyses, controlling for physical aggression, showed that average and high levels of effective coaching operated as a protective factor against stable high levels of relational aggression. Theoretical and practical implications for our understanding of the early development of relational aggression are discussed.

  11. Aggressiveness, violence, homicidality, homicide, and Lyme disease.

    Science.gov (United States)

    Bransfield, Robert C

    2018-01-01

    No study has previously analyzed aggressiveness, homicide, and Lyme disease (LD). Retrospective LD chart reviews analyzed aggressiveness, compared 50 homicidal with 50 non-homicidal patients, and analyzed homicides. Most aggression with LD was impulsive, sometimes provoked by intrusive symptoms, sensory stimulation or frustration and was invariably bizarre and senseless. About 9.6% of LD patients were homicidal with the average diagnosis delay of 9 years. Postinfection findings associated with homicidality that separated from the non-homicidal group within the 95% confidence interval included suicidality, sudden abrupt mood swings, explosive anger, paranoia, anhedonia, hypervigilance, exaggerated startle, disinhibition, nightmares, depersonalization, intrusive aggressive images, dissociative episodes, derealization, intrusive sexual images, marital/family problems, legal problems, substance abuse, depression, panic disorder, memory impairments, neuropathy, cranial nerve symptoms, and decreased libido. Seven LD homicides included predatory aggression, poor impulse control, and psychosis. Some patients have selective hyperacusis to mouth sounds, which I propose may be the result of brain dysfunction causing a disinhibition of a primitive fear of oral predation. LD and the immune, biochemical, neurotransmitter, and the neural circuit reactions to it can cause impairments associated with violence. Many LD patients have no aggressiveness tendencies or only mild degrees of low frustration tolerance and irritability and pose no danger; however, a lesser number experience explosive anger, a lesser number experience homicidal thoughts and impulses, and much lesser number commit homicides. Since such large numbers are affected by LD, this small percent can be highly significant. Much of the violence associated with LD can be avoided with better prevention, diagnosis, and treatment of LD.

  12. Clarifying Inconclusive Functional Analysis Results: Assessment and Treatment of Automatically Reinforced Aggression

    Science.gov (United States)

    Saini, Valdeep; Greer, Brian D.; Fisher, Wayne W.

    2016-01-01

    We conducted a series of studies in which multiple strategies were used to clarify the inconclusive results of one boy’s functional analysis of aggression. Specifically, we (a) evaluated individual response topographies to determine the composition of aggregated response rates, (b) conducted a separate functional analysis of aggression after high rates of disruption masked the consequences maintaining aggression during the initial functional analysis, (c) modified the experimental design used during the functional analysis of aggression to improve discrimination and decrease interaction effects between conditions, and (d) evaluated a treatment matched to the reinforcer hypothesized to maintain aggression. An effective yet practical intervention for aggression was developed based on the results of these analyses and from data collected during the matched-treatment evaluation. PMID:25891269

  13. Multiphoton imaging of low grade, high grade intraepithelial neoplasia and intramucosal invasive cancer of esophagus

    Science.gov (United States)

    Xu, Jian; Jiang, Liwei; Kang, Deyong; Wu, Xuejing; Xu, Meifang; Zhuo, Shuangmu; Zhu, Xiaoqin; Lin, Jiangbo; Chen, Jianxin

    2017-04-01

    Esophageal squamous cell carcinoma (ESCC) is devastating because of its aggressive lymphatic spread and clinical course. It is believed to occur through low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and intramucosal invasive cancer (IMC) before transforming to submucosal cancer. In particular, these early lesions (LGIN, HGIN and IMC), which involve no lymph node nor distant metastasis, can be cured by endoscopic treatment. Therefore, early identification of these lesions is important so as to offer a curative endoscopic resection, thus slowing down the development of ESCC. In this work, spectral information and morphological features of the normal esophageal mucosa are first studied. Then, the morphological changes of LGIN, HGIN and IMC are described. Lastly, quantitative parameters are also extracted by calculating the nuclear-to-cytoplasmic ratio of epithelial cells and the pixel density of collagen in the lamina propria. These results show that multiphoton microscopy (MPM) has the ability to identify normal esophageal mucosa, LGIN, HGIN and IMC. With the development of multiphoton endoscope systems for in vivo imaging, combined with a laser ablation system, MPM has the potential to provide immediate pathologic diagnosis and curative treatment of ESCC before the transformation to submucosal cancer in the future.

  14. Vitamin D and Related Genes, Race and Prostate Cancer Aggressiveness

    Science.gov (United States)

    2015-12-29

    serum vitamin D metabolites 25(OH)D and 1,25(OH)2D], and 2) plasma PTH/serum calcium homeostasis and serum phosphorous , and aggressiveness of disease...than EAs [5–9]. Vitamin D in humans is derived from cutaneous exposure to ultraviolet ( UV )-B rays from sunlight and the conversion of 7...Melanin blocks UV -B, and individuals with darker skin pigmentation re- quire longer time in the sun to produce equivalent amounts of 25(OH)D3 than

  15. Adolescents' Social Reasoning about Relational Aggression

    Science.gov (United States)

    Goldstein, Sara E.; Tisak, Marie S.

    2010-01-01

    We examined early adolescents' reasoning about relational aggression, and the links that their reasoning has to their own relationally aggressive behavior. Thinking about relational aggression was compared to thinking about physical aggression, conventional violations, and personal behavior. In individual interviews, adolescents (N = 103) rated…

  16. Brain-derived neurotrophic factor (BDNF) and its precursor (proBDNF) in genetically defined fear-induced aggression.

    Science.gov (United States)

    Ilchibaeva, Tatiana V; Kondaurova, Elena M; Tsybko, Anton S; Kozhemyakina, Rimma V; Popova, Nina K; Naumenko, Vladimir S

    2015-09-01

    The brain-derived neurotrophic factor (BDNF), its precursor (proBDNF) and BDNF mRNA levels were studied in the brain of wild rats selectively bred for more than 70 generations for either high level or for the lack of affective aggressiveness towards man. Significant increase of BDNF mRNA level in the frontal cortex and increase of BDNF level in the hippocampus of aggressive rats was revealed. In the midbrain and hippocampus of aggressive rats proBDNF level was increased, whereas BDNF/proBDNF ratio was reduced suggesting the prevalence and increased influence of proBDNF in highly aggressive rats. In the frontal cortex, proBDNF level in aggressive rats was decreased. Thus, considerable structure-specific differences in BDNF and proBDNF levels as well as in BDNF gene expression between highly aggressive and nonaggressive rats were shown. The data suggested the implication of BDNF and its precursor proBDNF in the mechanism of aggressiveness and in the creation of either aggressive or nonaggressive phenotype. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Thyroid cancer: experiences of Cancer Institute, Madras

    International Nuclear Information System (INIS)

    Kannan, R. Ravi; Mahajan, V.; Ganesh, M.S.; Ayyappan, S.; Suresh, V.; Suryasen, S.

    1999-01-01

    It has been long recognized that Thyroid Cancer (TC) envelopes under its umbrella a spectrum of cancers from the relatively indolent well differentiated papillary and follicular cancers to the aggressive and rapidly fatal anaplastic cancers. Medullary cancers fall in between the two extremes. Recently, poor prognostic variants of well-differentiated cancers have been described. There is also a move to define a group of poorly differentiated TC including the insular variants distinguishing them from anaplastic carcinomas. Of the 1168 patients with thyroid nodules seen at the Cancer Institute (WIA), Chennai between 1956 and 1996, 670 cases proved to be malignant either cytologically or histologically. This report is based on the follow-up of these patients which at 10 years was 75%

  18. Focal therapy in prostate cancer

    NARCIS (Netherlands)

    van den Bos, W.

    2016-01-01

    Interesting developments took place in the treatment of prostate cancer including focal therapy for less aggressive organ-confined prostate cancer. Fortunately, curative treatment is often still an option for patients suffering from the lower staged tumors. In carefully selected patients, the

  19. Are adolescents with internet addiction prone to aggressive behavior? The mediating effect of clinical comorbidities on the predictability of aggression in adolescents with internet addiction.

    Science.gov (United States)

    Lim, Jae-A; Gwak, Ah Reum; Park, Su Mi; Kwon, Jun-Gun; Lee, Jun-Young; Jung, Hee Yeon; Sohn, Bo Kyung; Kim, Jae-Won; Kim, Dai Jin; Choi, Jung-Seok

    2015-05-01

    Previous studies have reported associations between aggression and Internet addiction disorder (IAD), which has also been linked with anxiety, depression, and impulsiveness. However, the causal relationship between aggression and IAD has thus far not been clearly demonstrated. This study was designed to (a) examine the association between aggression and IAD and (b) investigate the mediating effects of anxiety, depression, and impulsivity in cases in which IAD predicts aggression or aggression predicts IAD. A total of 714 middle school students in Seoul, South Korea, were asked to provide demographic information and complete the Young's Internet Addiction Test (Y-IAT), the Buss-Perry Aggression Questionnaire, the Barratt Impulsiveness Scale-11, the State-Trait Anger Expression Inventory-2, the Beck Anxiety Inventory, the Beck Depression Inventory, and the Conners-Wells Adolescent Self-Report Scale. Three groups were identified based on the Y-IAT: the usual user group (n=487, 68.2%), the high-risk group (n=191, 26.8%), and the Internet addiction group (n=13, 1.8%). The data revealed a linear association between aggression and IAD such that one variable could be predicted by the other. According to the path analysis, the clinical scales (BAI, BDI, and CASS) had partial or full mediating effects on the ability of aggression to predict IAD, but the clinical scales had no mediating effect on the ability of IAD to predict aggression. The current findings suggest that adolescents with IAD seem to have more aggressive dispositions than do normal adolescents. If more aggressive individuals are clinically prone to Internet addiction, early psychiatric intervention may contribute to the prevention of IAD.

  20. Effect of doxorubicin/pluronic SP1049C on tumorigenicity, aggressiveness, DNA methylation and stem cell markers in murine leukemia.

    Directory of Open Access Journals (Sweden)

    Daria Y Alakhova

    Full Text Available Pluronic block copolymers are potent sensitizers of multidrug resistant cancers. SP1049C, a Pluronic-based micellar formulation of doxorubicin (Dox has completed Phase II clinical trial and demonstrated safety and efficacy in patients with advanced adenocarcinoma of the esophagus and gastroesophageal junction. This study elucidates the ability of SP1049C to deplete cancer stem cells (CSC and decrease tumorigenicity of cancer cells in vivo.P388 murine leukemia ascitic tumor was grown in BDF1 mice. The animals were treated with: (a saline, (b Pluronics alone, (c Dox or (d SP1049C. The ascitic cancer cells were isolated at different passages and examined for 1 in vitro colony formation potential, 2 in vivo tumorigenicity and aggressiveness, 3 development of drug resistance and Wnt signaling activation 4 global DNA methylation profiles, and 5 expression of CSC markers.SP1049C treatment reduced tumor aggressiveness, in vivo tumor formation frequency and in vitro clonogenic potential of the ascitic cells compared to drug, saline and polymer controls. SP1049C also prevented overexpression of BCRP and activation of Wnt-β-catenin signaling observed with Dox alone. Moreover, SP1049C significantly altered the DNA methylation profiles of the cells. Finally, SP1049C decreased CD133(+ P388 cells populations, which displayed CSC-like properties and were more tumorigenic compared to CD133(- cells.SP1049C therapy effectively suppresses the tumorigenicity and aggressiveness of P388 cells in a mouse model. This may be due to enhanced activity of SP1049C against CSC and/or altered epigenetic regulation restricting appearance of malignant cancer cell phenotype.

  1. Parenting styles and hormone levels as predictors of physical and indirect aggression in boys and girls.

    Science.gov (United States)

    Pascual-Sagastizabal, Eider; Azurmendi, Aitziber; Braza, Francisco; Vergara, Ana I; Cardas, Jaione; Sánchez-Martín, José R

    2014-01-01

    This study examines the relationship between parenting style, androgen levels, and measures of physical and indirect aggression. Peer ratings of aggression were obtained from 159 eight-year-old children (89 boys and 70 girls). Parenting styles (authoritative, authoritarian or permissive) were assessed using the Parenting Styles and Dimensions Questionnaire (PSDQ).Saliva samples were obtained from children and assayed for testosterone and androstenedione concentrations. A regression analysis revealed that high testosterone levels were associated with a higher level of physical aggression in boys with authoritarian mothers. Testosterone was also found to moderate the relationship between father's authoritarian parenting and physical aggression in girls, with both moderate and high levels being significant. In relation to indirect aggression, moderate and high levels of testosterone were associated with higher levels of this type of aggression in girls with permissive mothers. Our results highlight the importance of taking into account the interaction of biological and psychosocial variables when investigating aggressive behavior. © 2014 Wiley Periodicals, Inc.

  2. Sensitive period for developing a robust trait of appetitive aggression

    Directory of Open Access Journals (Sweden)

    Anke eKöbach

    2015-10-01

    Full Text Available Violent behaviour can be intrinsically rewarding; especially combatants fighting in current civil wars present with elevated traits of appetitive aggression. The majority of these fighters were recruited as children or adolescents. In the present study we test whether there is a developmental period where combatants are sensitive for developing a robust trait of appetitive aggression.We investigated 95 combatants in their demobilization process that were recruited at different ages in the Kivu regions of the eastern Democratic Republic of Congo. Using random forest with conditional inference trees, we identified recruitment at the ages from 16 and 17 years as being predictive of the level of appetitive aggression; the number of lifetime, perpetrated acts was the most important predictor. We conclude that high levels of appetitive aggression develop in ex-combatants, especially in those recruited during their middle to late teenage, which is a developmental period marked by a natural inclination to exercise physical force. Consequently, ex-combatants may remain vulnerable for aggressive behaviour patterns and re-recruitment unless they are provided alternative strategies for dealing with their aggression.

  3. Aggressive behavior and performance in the Tegu lizard Tupinambis merianae.

    Science.gov (United States)

    Herrel, Anthony; Andrade, Denis V; de Carvalho, José Eduardo; Brito, Ananda; Abe, Augusto; Navas, Carlos

    2009-01-01

    Aggression is an important component of behavior in many animals and may be crucial to providing individuals with a competitive advantage when resources are limited. Although much is known about the effects of catecholamines and hormones on aggression, relatively few studies have examined the effects of physical performance on aggression. Here we use a large, sexually dimorphic teiid lizard to test whether individuals that show high levels of physical performance (bite force) are also more aggressive toward a potential threat (i.e., a human approaching the lizard). Our results show that independent of their sex, larger individuals with higher bite forces were indeed more aggressive. Moreover, our data show that individuals with higher bite forces tend to show decreased escape responses and are slower, providing evidence for a trade-off between fight and flight abilities. As bite force increased dramatically with body size, we suggest that large body size and bite force may reduce the threshold for an individual to engage in an aggressive encounter, allowing it to potentially gain or maintain resources and fight off predators while minimizing the risk of injury.

  4. Patterns of change in early childhood aggressive-disruptive behavior: gender differences in predictions from early coercive and affectionate mother-child interactions.

    Science.gov (United States)

    McFadyen-Ketchum, S A; Bates, J E; Dodge, K A; Pettit, G S

    1996-10-01

    The present study focused on mother-child interaction predictors of initial levels and change in child aggressive and disruptive behavior at school from kindergarten to third grade. Aggression-disruption was measured via annual reports from teachers and peers. Ordinary least-squares regression was used to identify 8 separate child aggression trajectories, 4 for each gender: high initial levels with increases in aggression, high initial levels with decrease in aggression, low initial levels with increases in aggression, and low initial levels with decreases in aggression. Mother-child interaction measures of coercion and nonaffection collected prior to kindergarten were predictive of initial levels of aggression-disruption in kindergarten in both boys and girls. However, boys and girls differed in how coercion and nonaffection predicted change in aggression-disruption across elementary school years. For boys, high coercion and nonaffection were particularly associated with the high-increasing-aggression trajectory, but for girls, high levels of coercion and nonaffection were associated with the high-decreasing-aggression trajectory. This difference is discussed in the context of Patterson et al.'s coercion training theory, and the need for gender-specific theories of aggressive development is noted.

  5. A Two-Week Psychosocial Intervention Reduces Future Aggression and Incarceration in Clinically Aggressive Juvenile Offenders.

    Science.gov (United States)

    Kendall, Ashley D; Emerson, Erin M; Hartmann, William E; Zinbarg, Richard E; Donenberg, Geri R

    2017-12-01

    There is a largely unmet need for evidence-based interventions that reduce future aggression and incarceration in clinically aggressive juvenile offenders serving probation. We addressed this gap using a group randomized controlled trial. Offenders both with and without clinical aggression were included, enabling comparison of intervention effects. Juveniles 13 to 17 years old (N = 310, mean = 16 years, 90% African-American, 66% male) on probation were assigned to a 2-week intervention targeting psychosocial factors implicated in risky behavior (e.g., learning strategies to manage "hot" emotions that prompt risk taking) or to an equally intensive health promotion control. Participants completed aggression measures at baseline, 6-, and 12-month follow-up and reported on incarceration at 12 months. Spline regression tested symptom change. Among clinically aggressive offenders (n = 71), the intervention arm showed significantly greater reductions in aggression over the first 6 months compared with controls. Juveniles from the intervention no longer met clinical criteria, on average, but clinically significant symptoms persisted in the control group. By 12 months, participants from the intervention appeared to maintain treatment gains, but their symptom levels no longer differed significantly from those in the control. However, the intervention group was nearly 4 times less likely than controls to report incarceration. Intervention effects were significantly stronger for offenders with clinical than with nonclinical (n = 239) baseline aggression. A 2-week intervention expedited improvements in aggression and reduced incarceration in clinically aggressive juvenile offenders. The findings underscore the importance of directing intervention resources to the most aggressive youth. Clinical trial registration information-PHAT Life: Preventing HIV/AIDS Among Teens in Juvenile Justice (PHAT Life); http://clinicaltrials.gov/; NCT02647710. Copyright © 2017 American

  6. Gender Differences in Psychopathic Traits, Types, and Correlates of Aggression among Adjudicated Youth

    Science.gov (United States)

    Stickle, Timothy R.; Marini, Victoria A.; Thomas, Jamila N.

    2012-01-01

    The current study investigated gender differences in types and correlates of aggression among 150 adjudicated youth (M age = 15.2, SD = 1.4). In cluster analysis, consistent with past studies, one aggressive group characterized by moderate levels of reactive aggression and one characterized by high levels of proactive and reactive aggression…

  7. Brain structures and neurotransmitters regulating aggression in cats: implications for human aggression.

    Science.gov (United States)

    Gregg, T R; Siegel, A

    2001-01-01

    1. Violence and aggression are major public health problems. 2. The authors have used techniques of electrical brain stimulation, anatomical-immunohistochemical techniques, and behavioral pharmacology to investigate the neural systems and circuits underlying aggressive behavior in the cat. 3. The medial hypothalamus and midbrain periaqueductal gray are the most important structures mediating defensive rage behavior, and the perifornical lateral hypothalamus clearly mediates predatory attack behavior. The hippocampus, amygdala, bed nucleus of the stria terminalis, septal area, cingulate gyrus, and prefrontal cortex project to these structures directly or indirectly and thus can modulate the intensity of attack and rage. 4. Evidence suggests that several neurotransmitters facilitate defensive rage within the PAG and medial hypothalamus, including glutamate, Substance P, and cholecystokinin, and that opioid peptides suppress it; these effects usually depend on the subtype of receptor that is activated. 5. A key recent discovery was a GABAergic projection that may underlie the often-observed reciprocally inhibitory relationship between these two forms of aggression. 6. Recently, Substance P has come under scrutiny as a possible key neurotransmitter involved in defensive rage, and the mechanism by which it plays a role in aggression and rage is under investigation. 7. It is hoped that this line of research will provide a better understanding of the neural mechanisms and substrates regulating aggression and rage and thus establish a rational basis for treatment of disorders associated with these forms of aggression.

  8. Pubertal development and prostate cancer risk

    DEFF Research Database (Denmark)

    Bonilla, Carolina; Lewis, Sarah J; Martin, Richard M

    2016-01-01

    , 0.91-1.00) and prostate cancer-specific mortality (hazard ratio amongst cases, per tertile: 0.94; 95 % CI, 0.90-0.98), but not with disease grade. CONCLUSIONS: Older age at sexual maturation is causally linked to a reduced risk of later prostate cancer, especially aggressive disease.......BACKGROUND: Epidemiological studies have observed a positive association between an earlier age at sexual development and prostate cancer, but markers of sexual maturation in boys are imprecise and observational estimates are likely to suffer from a degree of uncontrolled confounding. To obtain...... to a difference of one Tanner stage between pubertal boys of the same age) was associated with a 77 % (95 % CI, 43-91 %) reduced odds of high Gleason prostate cancer. In PRACTICAL, the puberty genetic score was associated with prostate cancer stage (OR of advanced vs. localized cancer, per tertile: 0.95; 95 % CI...

  9. Policy Implications of Present Knowledge on the Development and Prevention of Physical Aggression

    OpenAIRE

    Junger, Marianne; Feder, Lynette; Cote, Sylvana M.

    2007-01-01

    Research indicates that children are born with aggressive tendencies which they learn to control through early socialization. A small group, however, shows high aggression levels early on which remain stable throughout their life. Physical aggression is an epiphenomenon in a wide variety of antisocial behaviour, which wrecks the life of the individual as well as having large and negative consequences on society. The premise of this article is that physical aggression can be successfully influ...

  10. The nature of human aggression.

    Science.gov (United States)

    Archer, John

    2009-01-01

    Human aggression is viewed from four explanatory perspectives, derived from the ethological tradition. The first consists of its adaptive value, which can be seen throughout the animal kingdom, involving resource competition and protection of the self and offspring, which has been viewed from a cost-benefit perspective. The second concerns the phylogenetic origin of aggression, which in humans involves brain mechanisms that are associated with anger and inhibition, the emotional expression of anger, and how aggressive actions are manifest. The third concerns the origin of aggression in development and its subsequent modification through experience. An evolutionary approach to development yields conclusions that are contrary to the influential social learning perspective, notably that physical aggression occurs early in life, and its subsequent development is characterized by learned inhibition. The fourth explanation concerns the motivational mechanisms controlling aggression: approached from an evolutionary background, these mechanisms range from the inflexible reflex-like responses to those incorporating rational decision-making.

  11. Identification and Validation of PCAT14 as Prognostic Biomarker in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Sudhanshu Shukla

    2016-08-01

    Full Text Available Rapid advances in the discovery of long noncoding RNAs (lncRNAs have identified lineage- and cancer-specific biomarkers that may be relevant in the clinical management of prostate cancer (PCa. Here we assembled and analyzed a large RNA-seq dataset, from 585 patient samples, including benign prostate tissue and both localized and metastatic PCa to discover and validate differentially expressed genes associated with disease aggressiveness. We performed Sample Set Enrichment Analysis (SSEA and identified genes associated with low versus high Gleason score in the RNA-seq database. Comparing Gleason 6 versus 9+ PCa samples, we identified 99 differentially expressed genes with variable association to Gleason grade as well as robust expression in prostate cancer. The top-ranked novel lncRNA PCAT14, exhibits both cancer and lineage specificity. On multivariate analysis, low PCAT14 expression independently predicts for BPFS (P = .00126, PSS (P = .0385, and MFS (P = .000609, with trends for OS as well (P = .056. An RNA in-situ hybridization (ISH assay for PCAT14 distinguished benign vs malignant cases, as well as high vs low Gleason disease. PCAT14 is transcriptionally regulated by AR, and endogenous PCAT14 overexpression suppresses cell invasion. Thus, Using RNA-sequencing data we identify PCAT14, a novel prostate cancer and lineage-specific lncRNA. PCAT14 is highly expressed in low grade disease and loss of PCAT14 predicts for disease aggressiveness and recurrence.

  12. Effects of Viewing Relational Aggression on Television on Aggressive Behavior in Adolescents: A Three-Year Longitudinal Study

    Science.gov (United States)

    Coyne, Sarah M.

    2016-01-01

    Most researchers on media and aggression have examined the behavioral effects of viewing physical aggression in the media. Conversely, in the current study, I examined longitudinal associations between viewing "relational aggression" on TV and subsequent aggressive behavior. Participants included 467 adolescents who completed a number of…

  13. The Effects of Pornography on Aggressive Behavior.

    Science.gov (United States)

    Stacy, Lauri L.

    This document reviews existing empirical research on the effect of pornography on aggressive behavior. Two types of pornography are distinguished: aggressive pornography and non-aggressive pornography. Conclusions drawn from the research review are presented, including: (1) aggressive pornograpy consistently increases aggressive attitudes and…

  14. Trends in incidence, treatment and survival of aggressive B-cell lymphoma in the Netherlands 1989-2010

    NARCIS (Netherlands)

    D.E. Issa (Djamila); S.A.M. van de Schans (Saskia); M.E.D. Chamuleau (Martine); H.E. Karim-Kos (Henrike); M.J. Wondergem (Marielle); P.C. Huijgens (Peter); J.W.W. Coebergh (Jan Willem); S. Zweegman (Sonja); O.J. Visser (Otto)

    2015-01-01

    textabstractOnly a small number of patients with aggressive B-cell lymphoma take part in clinical trials, and elderly patients in particular are under-represented. Therefore, we studied data of the population-based nationwide Netherlands Cancer Registry to determine trends in incidence, treatment

  15. The associations between aggressive behaviors and internet addiction and online activities in adolescents.

    Science.gov (United States)

    Ko, Chih-Hung; Yen, Ju-Yu; Liu, Shu-Chun; Huang, Chi-Fen; Yen, Cheng-Fang

    2009-06-01

    To evaluate (a) the association between Internet addiction and aggressive behaviors, as well as the moderating effects of gender, school, and depression on this association; and (b) to evaluate the association between Internet activities and aggressive behaviors. A total of 9405 adolescents were recruited into this study and completed the questionnaires. Their aggressive behaviors, with or without Internet addiction, Internet activities, demographic data, with or without depression, self-esteem, family function, and the watching of violent TV were assessed. The results demonstrated that after controlling for the effects of shared associated factors and watching violent TV programs, adolescents with Internet addiction were more likely to have aggressive behaviors during the previous year. The association was more significant among adolescents in junior high schools than in senior high/vocational schools. Online chatting, adult sex Web viewing, online gaming, online gambling, and Bulletin Board System were all associated with aggressive behaviors. The results suggest that preventive programs for aggressive behaviors should pay attention to Internet addiction among adolescents. Also, intervention to prevent the effects of Internet addiction on aggressive behaviors should be conducted as early as possible.

  16. Multiparametric magnetic resonance imaging in the detection of prostate cancer

    International Nuclear Information System (INIS)

    Durmus, T.; Baur, A.; Hamm, B.

    2014-01-01

    Prostate cancer is the most common malignancy in men, but only about 10 % of patients die from that cancer. Recent studies suggest that not all patients benefit from a radical therapeutic approach. When prostate cancer is suspected, magnetic resonance imaging (MRI) can make an important contribution to cancer localization within the prostate. Many studies show that T2-weighted morphologic imaging should be supplemented by multiparametric MRI techniques including diffusion-weighted imaging, contrast-enhanced sequences, and MR spectroscopy. This approach detects aggressive prostate cancer with high sensitivity and specificity. The findings of multiparametric MRI additionally contribute information to the assessment of cancer aggressiveness. The use of these multiparametric MRI techniques will gain an increasing role in the clinical management of prostate cancer patients. They can help in establishing a definitive diagnosis with a minimum of invasiveness and may also contribute to optimal individualized treatment. This review article presents the different techniques of multiparametric MRI and discusses their contribution to the detection of prostate cancer. Moreover, this review outlines an objective approach to image interpretation and structured reporting of MRI findings using the PI-RADS criteria. The review concludes with an outline of approaches to prostate biopsy on the basis of MRI (transrectal ultrasound, direct MRI guidance of tissue sampling, and MRI-ultrasound fusion biopsy) and emerging future uses of MRI in the planning of focal treatment options and in the active surveillance of patients diagnosed with prostate cancer. (orig.)

  17. The associations between parenting styles and proactive and reactive aggression in Hong Kong children and adolescents.

    Science.gov (United States)

    Gao, Yu; Zhang, Wei; Fung, Annis Lai Chu

    2015-12-01

    Previous research suggests that reactive and proactive aggression may be differentially related to family contextual (e.g. parenting practices) factors. However, the existing research has focused largely on children and adolescents from Western countries, and no study has examined the parenting-aggression association using a parenting style measure sensitive to Asian culture. In this study parenting styles (i.e. warmth, control and guan/training) and proactive and reactive aggression were assessed in a large sample of school children in Hong Kong, China (N = 4,175, mean age = 11.75). We found that: (a) both low warmth (in boys only) and guan (i.e. high expectation and close supervision, in both boys and girls) were associated with elevated parent-reported proactive aggression, (b) high restrictive control (i.e. dominating and rejecting) was associated with high reactive aggression (in both boys and girls) based on parent- or child-report data, and with high proactive aggression (in boys only) based on parent-report data, and (c) guan was also positively associated with parent-reported reactive aggression. Findings provide more information about the Parenting Inventory using a large Asian sample, and extend existing research on familial correlates of different types of aggression. © 2014 International Union of Psychological Science.

  18. Combinatorial nanomedicines for colon cancer therapy.

    Science.gov (United States)

    Anitha, A; Maya, S; Sivaram, Amal J; Mony, U; Jayakumar, R

    2016-01-01

    Colon cancer is one of the major causes of cancer deaths worldwide. Even after surgical resection and aggressive chemotherapy, 50% of colorectal carcinoma patients develop recurrent disease. Thus, the rationale of developing new therapeutic approaches to improve the current chemotherapeutic regimen would be highly recommended. There are reports on the effectiveness of combination chemotherapy in colon cancer and it has been practiced in clinics for long time. These approaches are associated with toxic side effects. Later, the drug delivery research had shown the potential of nanoencapsulation techniques and active targeting as an effective method to improve the effectiveness of chemotherapy with less toxicity. This current focus article provides a brief analysis of the ongoing research in the colon cancer area using the combinatorial nanomedicines and its outcome. © 2015 Wiley Periodicals, Inc.

  19. Aggressive and Nonaggressive Children's Moral Judgments and Moral Emotion Attributions in Situations Involving Retaliation and Unprovoked Aggression

    Science.gov (United States)

    Gasser, Luciano; Malti, Tina; Gutzwiller-Helfenfinger, Eveline

    2012-01-01

    The authors investigated 7- and 9-year-old children's moral understanding of retaliation as compared to unprovoked aggression with regard to their aggressive behavior status. Based on peer ratings, 48 children were selected as overtly aggressive and 91 as nonaggressive. Their moral understanding of retaliation and unprovoked aggression was…

  20. Associations of Neighborhood and Family Factors with Trajectories of Physical and Social Aggression During Adolescence

    Science.gov (United States)

    Karriker-Jaffe, Katherine J.; Foshee, Vangie A.; Ennett, Susan T.; Suchindran, Chirayath

    2013-01-01

    Adolescents develop within multiple contexts that synergistically influence their behavior and health. To understand the simultaneous influence of neighborhood and family contexts on adolescents, this study examined relationships of neighborhood socioeconomic disadvantage, neighborhood social disorganization, family conflict, parent-child bonding and parental control with trajectories of physical and social aggression. The sample included 5,118 adolescents between ages 11 and 18 (50% female, 52% Caucasian) living in predominantly rural areas. Multilevel growth curve models showed an interaction between neighborhood disadvantage, family conflict and gender on the physical aggression trajectories. The interaction suggested more rapid processes of both increase in and desistance from physical aggression over time for boys with high neighborhood disadvantage and high family conflict, as well as a higher starting point, more gradual increase and slower process of desistance over time for girls in similar neighborhood and family contexts. Less parent-child bonding and less parental control also were associated with higher initial levels of physical aggression. For social aggression, an interaction between family conflict and gender showed girls with high family conflict had the highest initial levels of social aggression, with a more gradual increase over time for these girls compared to their male counterparts in high-conflict families or their female counterparts in low-conflict families. Less parent-child bonding was associated with higher initial levels and a faster increase over time of social aggression, and less parental control was associated with higher initial levels of social aggression. The findings suggest early family-based interventions may help prevent perpetration of both physical and social aggression during adolescence. PMID:23054352

  1. “Blurred Lines?”1 Sexual Aggression and Barroom Culture

    Science.gov (United States)

    Graham, Kathryn; Bernards, Sharon; Osgood, D. Wayne; Abbey, Antonia; Parks, Michael; Flynn, Andrea; Dumas, Tara; Wells, Samantha

    2014-01-01

    patrons and staff that support sexual aggression and better management of the highly sexualized and sexist environments of most bars. PMID:24588839

  2. Aggression and violence and the achievement gap among urban minority youth.

    Science.gov (United States)

    Basch, Charles E

    2011-10-01

    To outline the prevalence and disparities of aggression and violence among school-aged urban minority youth, causal pathways through which aggression and violence adversely affects academic achievement, and proven or promising approaches for schools to address these problems. Literature review. Recent national data indicate that among students aged 12-18, approximately 628,200 violent crimes and 868,100 thefts occurred. Physical fighting was more commonly reported by Blacks and Hispanics (44.7% and 40.4%, respectively) than Whites (31.7%). In-school threats and injuries were nearly twice as prevalent in cities as in suburbs and towns or rural areas (10% vs 6% and 5%, respectively). Associations between exposure to and exhibition of aggression and violence and unfavorable educational outcomes are well documented. Causal pathways through which aggression and violence impede learning include cognition, school connectedness, and absenteeism. Disruptive classroom behavior is a well-recognized and significant impediment to teaching and learning. Compelling research has shown that various school-based programs can significantly reduce the nature and extent of aggressive and violent behaviors. Violence and aggressive behavior are highly and disproportionately prevalent among school-aged urban minority youth, have a negative impact on academic achievement by adversely affecting cognition, school connectedness, and absenteeism, and effective practices are available for schools to address this problem. Once the domain of criminal justice, aggression and violence are now recognized as an appropriate and important focus of the education and public health systems. Implementing evidence-based school policies and programs to reduce aggression and violence must be a high priority to help close the achievement gap. © 2011, American School Health Association.

  3. The Aggression-Inhibiting and Aggression-Facilitating Influence of Heightened Sexual Arousal.

    Science.gov (United States)

    Baron, Robert A.; Bell, Paul A.

    Eighty-six undergraduate males participated in an experiment designed to investigate the impact of various types of erotic stimuli upon aggression. On the basis of previous research, it was hypothesized that exposure to mild erotic stimuli would tend to inhibit subsequent aggression, while exposure to more arousing stimuli of this type would…

  4. The experience of aggression by female teachers in the workplace ...

    African Journals Online (AJOL)

    High stress levels fuels aggression in the workplace. It was observed that female teachers often experience aggression in the workplace. This has a negative effect on their overall sense of well-being as well as their mental health. A purposive sample was selected through two private schools in Gauteng, South Africa, and ...

  5. Maximizing outcomes in genitourinary cancers across the treatment continuum.

    LENUS (Irish Health Repository)

    Fitzpatrick, John M

    2011-04-01

    Key controversies concerning the management of genitourinary cancers across the treatment continua were discussed at the second annual Interactive Genitourinary Cancer Conference (IGUCC) held in February 2010 in Athens, Greece. Prostate cancer is the most common form of cancer among western men and prevention strategies are needed. Trials evaluating 5α-reductase inhibitors have reported beneficial and clinically meaningful results, but uptake remains low for primary prostate cancer prevention. Prostate cancer detection programmes are also important as curative treatments for advanced disease are unavailable. Two large landmark randomized controlled trials reported conflicting results concerning screening efficacy and uncovered high levels of over-diagnosis and potential over-treatment. Tailored management strategies after diagnosis are important and predictive markers that distinguish between aggressive and indolent tumours are needed. The majority of newly diagnosed cases of prostate cancer are clinically localized. Active surveillance of favourable risk patients may be beneficial in the intermediate term, while an integrated approach of multi-modality therapy in patients with adverse features is recommended. The benefits of new technologies such as high-intensity focused ultrasound (HIFU) and robotic prostatectomy have not been established in prospective randomized trials vs current standards of care. A multidisciplinary approach is essential to evolving the management of advanced prostate cancer into a chronic disease paradigm. Docetaxel plus prednisone is the standard first-line chemotherapy for patients with metastatic castration-resistant prostate cancer (mCRPC), but the optimal timing of chemotherapy initiation has not been addressed in randomized clinical trials. Retrospective analyses suggest that asymptomatic patients with adverse prognostic factors for survival may also benefit from receiving chemotherapy. Bladder cancer is a common malignancy and the

  6. Aggression in children and youth towards crime.

    OpenAIRE

    ŠTEFFLOVÁ, Eva

    2013-01-01

    This thesis deals with aggressive children and youth, which leads to crime. It deals with the causes of aggression, factors that influence aggression, but also the type of aggression. The practical part contains specific case studies of individuals whose aggression was one of the causes of crime.

  7. Aggression, impulsivity, and suicide behavior: a review of the literature.

    Science.gov (United States)

    Gvion, Yari; Apter, Alan

    2011-01-01

    This article reviews the literature on the association between impulsivity aggression and suicide. The key words impulsivity, aggression, and suicide were entered into the pubmed, psychlit, and proqest databases. Significant articles were scrutinized for relevant information. Impulsivity and aggression are highly correlated with suicidal behavior across psychiatric samples, nosological borders, and non-psychiatric populations. Impulsivity and aggression are related but the nature of this relationship remains unclear. The literature is confusing and contradictory. This is probably due to the difficulty in defining and separating out these concepts and the fact that there is much overlap between them. Future research should aim at clarifying and refining these concepts as well as their link to all the different forms of suicidal behavior.

  8. Brachytherapy boost and cancer-specific mortality in favorable high-risk versus other high-risk prostate cancer

    Directory of Open Access Journals (Sweden)

    Vinayak Muralidhar

    2016-02-01

    Full Text Available Purpose : Recent retrospective data suggest that brachytherapy (BT boost may confer a cancer-specific survival benefit in radiation-managed high-risk prostate cancer. We sought to determine whether this survival benefit would extend to the recently defined favorable high-risk subgroup of prostate cancer patients (T1c, Gleason 4 + 4 = 8, PSA 20 ng/ml. Material and methods: We identified 45,078 patients in the Surveillance, Epidemiology, and End Results database with cT1c-T3aN0M0 intermediate- to high-risk prostate cancer diagnosed 2004-2011 treated with external beam radiation therapy (EBRT only or EBRT plus BT. We used multivariable competing risks regression to determine differences in the rate of prostate cancer-specific mortality (PCSM after EBRT + BT or EBRT alone in patients with intermediate-risk, favorable high-risk, or other high-risk disease after adjusting for demographic and clinical factors. Results : EBRT + BT was not associated with an improvement in 5-year PCSM compared to EBRT alone among patients with favorable high-risk disease (1.6% vs. 1.8%; adjusted hazard ratio [AHR]: 0.56; 95% confidence interval [CI]: 0.21-1.52, p = 0.258, and intermediate-risk disease (0.8% vs. 1.0%, AHR: 0.83, 95% CI: 0.59-1.16, p = 0.270. Others with high-risk disease had significantly lower 5-year PCSM when treated with EBRT + BT compared with EBRT alone (3.9% vs. 5.3%; AHR: 0.73; 95% CI: 0.55-0.95; p = 0.022. Conclusions : Brachytherapy boost is associated with a decreased rate of PCSM in some men with high-risk prostate cancer but not among patients with favorable high-risk disease. Our results suggest that the recently-defined “favorable high-risk” category may be used to personalize therapy for men with high-risk disease.

  9. 5-HT1A receptor gene silencers Freud-1 and Freud-2 are differently expressed in the brain of rats with genetically determined high level of fear-induced aggression or its absence.

    Science.gov (United States)

    Kondaurova, Elena M; Ilchibaeva, Tatiana V; Tsybko, Anton S; Kozhemyakina, Rimma V; Popova, Nina K; Naumenko, Vladimir S

    2016-09-01

    Serotonin 5-HT1A receptor is known to play a crucial role in the mechanisms of genetically defined aggression. In its turn, 5-HT1A receptor functional state is under control of multiple factors. Among others, transcriptional factors Freud-1 and Freud-2 are known to be involved in the repression of 5-HT1A receptor gene expression. However, implication of these factors in the regulation of behavior is unclear. Here, we investigated the expression of 5-HT1A receptor and silencers Freud-1 and Freud-2 in the brain of rats selectively bred for 85 generations for either high level of fear-induced aggression or its absence. It was shown that Freud-1 and Freud-2 levels were different in aggressive and nonaggressive animals. Freud-1 protein level was decreased in the hippocampus, whereas Freud-2 protein level was increased in the frontal cortex of highly aggressive rats. There no differences in 5-HT1A receptor gene expression were found in the brains of highly aggressive and nonaggressive rats. However, 5-HT1A receptor protein level was decreased in the midbrain and increased in the hippocampus of highly aggressive rats. These data showed the involvement of Freud-1 and Freud-2 in the regulation of genetically defined fear-induced aggression. However, these silencers do not affect transcription of the 5-HT1A receptor gene in the investigated rats. Our data indicate the implication of posttranscriptional rather than transcriptional regulation of 5-HT1A receptor functional state in the mechanisms of genetically determined aggressive behavior. On the other hand, the implication of other transcriptional regulators for 5-HT1A receptor gene in the mechanisms of genetically defined aggression could be suggested. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Inhibition of nuclear waste solutions containing multiple aggressive anions

    International Nuclear Information System (INIS)

    Congdon, J.W.

    1987-01-01

    The inhibition of localized corrosion of carbon steel in caustic, high-level radioactive waste solutions was studied using cyclic potentiodynamic polarization scans, supplemented by partially immersed coupon tests. The electrochemical tests provided a rapid and accurate means of determining the relationship between the minimum inhibitor requirements and the concentration of the aggressive anions in this system. Nitrate, sulfate, chloride, and fluoride were identified as aggressive anions, however, no synergistic effects were observed between these anions. This observation may have important theoretical implications because it tends to contradict the behavior of aggressive anions as predicted by existing theories for localized corrosion. 10 refs., 5 figs., 2 tabs

  11. Role Stress and Aggression among Young Adults: The Moderating Influences of Gender and Adolescent Aggression

    Science.gov (United States)

    Liu, Ruth X.; Kaplan, Howard B.

    2004-01-01

    Using data provided by a panel of non-Hispanic white respondents, this study explored whether aggressive response to severe role stress during early adulthood depends on gender and on an adolescent history of aggression. Logistic regression analysis yielded these findings: Men who reported aggression during early adolescence were significantly…

  12. Loss of Dickkopf 3 Promotes the Tumorigenesis of Basal Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Eva Lorsy

    Full Text Available Dickkopf 3 (DKK3 has been associated with tumor suppression of various tumor entities including breast cancer. However, the functional impact of DKK3 on the tumorigenesis of distinct molecular breast cancer subtypes has not been considered so far. Therefore, we initiated a study analyzing the subtype-specific DKK3 expression pattern as well as its prognostic and functional impact with respect to breast cancer subtypes. Based on three independent tissue cohorts including one in silico dataset (n = 30, n = 463 and n = 791 we observed a clear down-regulation of DKK3 expression in breast cancer samples compared to healthy breast tissue controls on mRNA and protein level. Interestingly, most abundant reduction of DKK3 expression was detected in the highly aggressive basal breast cancer subtype. Analyzing a large in silico dataset comprising 3,554 cases showed that low DKK3 mRNA expression was significantly associated with reduced recurrence free survival (RFS of luminal and basal-like breast cancer cases. Functionally, DKK3 re-expression in human breast cancer cell lines led to suppression of cell growth possibly mediated by up-regulation of apoptosis in basal-like but not in luminal-like breast cancer cell lines. Moreover, ectopic DKK3 expression in mesenchymal basal breast cancer cells resulted in partial restoration of epithelial cell morphology which was molecularly supported by higher expression of epithelial markers like E-Cadherin and down-regulation of mesenchymal markers such as Snail 1. Hence, we provide evidence that down-regulation of DKK3 especially promotes tumorigenesis of the aggressive basal breast cancer subtype. Further studies decoding the underlying molecular mechanisms of DKK3-mediated effects may help to identify novel targeted therapies for this clinically highly relevant breast cancer subtype.

  13. Aggression on inpatient units: Clinical characteristics and consequences.

    Science.gov (United States)

    Renwick, Laoise; Stewart, Duncan; Richardson, Michelle; Lavelle, Mary; James, Karen; Hardy, Claire; Price, Owen; Bowers, Len

    2016-08-01

    Aggression and violence are widespread in UK Mental Health Trusts, and are accompanied by negative psychological and physiological consequences for both staff and other patients. Patients who are younger, male, and have a history of substance use and psychosis diagnoses are more likely to display aggression; however, patient factors are not solely responsible for violence, and there are complex circumstances that lead to aggression. Indeed, patient-staff interactions lead to a sizeable portion of aggression and violence on inpatient units, thus they cannot be viewed without considering other forms of conflict and containment that occur before, during, and after the aggressive incident. For this reason, we examined sequences of aggressive incidents in conjunction with other conflict and containment methods used to explore whether there were particular profiles to aggressive incidents. In the present study, 522 adult psychiatric inpatients from 84 acute wards were recruited, and there were 1422 incidents of aggression (verbal, physical against objects, and physical). Cluster analysis revealed that aggressive incident sequences could be classified into four separate groups: solo aggression, aggression-rule breaking, aggression-medication, and aggression-containment. Contrary to our expectations, we did not find physical aggression dominant in the aggression-containment cluster, and while verbal aggression occurred primarily in solo aggression, physical aggression also occurred here. This indicates that the management of aggression is variable, and although some patient factors are linked with different clusters, these do not entirely explain the variation. © 2016 Australian College of Mental Health Nurses Inc.

  14. Oxytocin mechanisms of stress response and aggression in a territorial finch.

    Science.gov (United States)

    Goodson, James L; Schrock, Sara E; Kingsbury, Marcy A

    2015-03-15

    All jawed vertebrates produce a form of oxytocin (OT), and in birds, mammals and fish, OT is strongly associated with affiliation. However, remarkably few data are available on the roles of OT and OT receptors (OTRs) in aggression. Because OT and OTRs exert anxiolytic effects in mammals (although context-specific) and modulate stress coping, we hypothesized that OTR activation is at least permissive for territorial aggression. Indeed, we find that peripheral injections of an OTR antagonist significantly reduce male-male and female-female aggression in a highly territorial finch. This finding suggests the hypothesis that aggression is accompanied by an increase in transcriptional (Fos) activity of OT neurons, but contrary to this hypothesis, we find that dominant male residents do not elevate OT-Fos colocalization following an aggressive encounter and that OT-Fos colocalization in the preoptic area and hypothalamus correlates negatively with aggression. Furthermore, OT-Fos colocalization increases dramatically in males that were aggressively subjugated or pursued by a human hand, likely reflecting OT modulation of stress response. Because OT inhibits the hypothalamo-pituitary-adrenal axis, the antagonist effects may reflect the fact that aggressive birds and mammals tend to be hyporesponsive to stress. If this is correct, then 1) the observed effects of OTR antagonism may reflect alterations in corticosterone feedback to the brain rather than centrally mediated OTR effects, and 2) the negative correlation between OT-Fos colocalization and aggression may reflect the fact that more aggressive, stress hyporesponsive males require less inhibition of the hypothalamo-pituitary-adrenal axis than do less aggressive males, despite the requirement of that inhibition for the normal display of aggression. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Personality correlates of revenge-seeking: Multidimensional links to physical aggression, impulsivity, and aggressive pleasure.

    Science.gov (United States)

    Chester, David S; DeWall, C Nathan

    2018-05-01

    People differ in how much they seek retribution for interpersonal insults, slights, rejections, and other antagonistic actions. Identifying individuals who are most prone towards such revenge-seeking is a theoretically-informative and potentially violence-reducing endeavor. However, we have yet to understand the extent to which revenge-seeking individuals exhibit specific features of aggressiveness, impulsivity, and what motivates their hunt for retribution. Toward this end, we conducted three studies (total N = 673), in which revenge-seeking was measured alongside these other constructs. Analyses repeatedly demonstrated that revenge-seeking was associated with greater physical (but not verbal) aggressiveness, anger, and hostility. Revenge-seeking's link to physical aggression was partially accounted for by impulses toward enjoying aggression and the tendency to use aggression to improve mood. Dominance analyses revealed that sadism explained the most variance in revenge-seeking. Revenge-seeking was associated with greater impulsive responses to negative and positive affect, as well as greater premeditation of behavior. These findings paint a picture of revenge-seekers as physically aggressive curators of anger, whose retributive acts are performed with planned malice and motivated by the act's entertaining and therapeutic qualities. © 2017 Wiley Periodicals, Inc.

  16. An investigation of the mechanism underlying teacher aggression: Testing I3 theory and the General Aggression Model.

    Science.gov (United States)

    Montuoro, Paul; Mainhard, Tim

    2017-12-01

    Considerable research has investigated the deleterious effects of teachers responding aggressively to students who misbehave, but the mechanism underlying this dysfunctional behaviour remains unknown. This study investigated whether the mechanism underlying teacher aggression follows I 3 theory or General Aggression Model (GAM) metatheory of human aggression. I 3 theory explains exceptional, catastrophic events of human aggression, whereas the GAM explains common human aggression behaviours. A total of 249 Australian teachers participated in this study, including 142 primary school teachers (Mdn [age] = 35-39 years; Mdn [years teaching] = 10-14 years; 84% female) and 107 secondary school teachers (Mdn [age] = 45-49 years; Mdn [years teaching] = 15-19 years; 65% female). Participants completed four online self-report questionnaires, which assessed caregiving responsiveness, trait self-control, misbehaviour provocation, and teacher aggression. Analyses revealed that the GAM most accurately captures the mechanism underlying teacher aggression, with lower caregiving responsiveness appearing to indirectly lead to teacher aggression via higher misbehaviour provocation and lower trait self-control in serial, controlling for gender, age, years teaching, and current role (primary, secondary). This study indicates that teacher aggression proceeds from 'the person in the situation'. Specifically, lower caregiving responsiveness appears to negatively shape a teacher's affective, cognitive, and arousal states, which influence how they perceive and interpret student misbehaviour. These internal states, in turn, appear to negatively influence appraisal and decision processes, leading to immediate appraisal and impulsive actions. These results raise the possibility that teacher aggression is a form of countertransference. © 2017 The British Psychological Society.

  17. False memories for aggressive acts.

    Science.gov (United States)

    Laney, Cara; Takarangi, Melanie K T

    2013-06-01

    Can people develop false memories for committing aggressive acts? How does this process compare to developing false memories for victimhood? In the current research we used a simple false feedback procedure to implant false memories for committing aggressive acts (causing a black eye or spreading malicious gossip) or for victimhood (receiving a black eye). We then compared these false memories to other subjects' true memories for equivalent events. False aggressive memories were all too easy to implant, particularly in the minds of individuals with a proclivity towards aggression. Once implanted, the false memories were indistinguishable from true memories for the same events, on several dimensions, including emotional content. Implications for aggression-related memory more generally as well as false confessions are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. [Neurochemistry of impulsiveness and aggression].

    Science.gov (United States)

    Vetulani, Jerzy

    2013-01-01

    Aggression is the most frequent social reaction among animals and men, and plays an important role in survival of the fittest. The change of social conditions in the course of development of human civilisation rendered some forms of aggression counter-adaptive, but the neurobiological mechanism of expression of aggression have not fundamentally changed in the last stages of human evolution. The two different kinds of aggression: emotional, serving mainly as a threat, and rational, predatory, serving for the attainment of goal in the most effective way, have different anatomical and neurobiological background and reciprocally inhibit each other. Aggression is modulated by several neurotransmitter and hormonal systems, of which the key role is seemingly played by testosterone, a hormone involved in domination behaviour, and serotonin, whose deficit results in increased impulsiveness.

  19. The Influence of Neighborhood Characteristics and Parenting Practices on Academic Problems and Aggression Outcomes among Moderately to Highly Aggressive Children

    Science.gov (United States)

    Barry, Tammy D.; Lochman, John E.; Fite, Paula J.; Wells, Karen C.; Colder, Craig R.

    2012-01-01

    The current study utilized a longitudinal design to examine the effects of neighborhood and parenting on 120 at-risk children's academic and aggressive outcomes, concurrently and at two later timepoints during the transition to middle school. Random effects regression models were estimated to examine whether neighborhood characteristics and harsh…

  20. Socialna inteligentnost, empatija in agresivno vedenje: is a stereotype of aggressive individual as socially incompetent inaccurate?: je stereotipna predstava agresivnega človeka kot socialno nekompetentnega zavajajoča?: Social intelligence, empathy, and aggressive behavior:

    OpenAIRE

    Avsec, Andreja; Vidmar, Marina

    2011-01-01

    In the present research, which was carried out on 187 high school students (86 girls and 101 boys), we examined to what extent different aspects of social intelligence contribute to indirect and direct aggression and to what extent empathy can act as a mitigator of aggression. We used The Aggression Questionnaire to measure physical aggression, IAS-A (which includes Social Exclusion, Use of Malicious Humour and Guilt Induction sub-scales) to measure indirect aggression, TSIS (which includes S...

  1. Aggressive Event Incidence using the Staff Observation of Aggression Scale-Revised (SOAS-R): A Longitudinal Study.

    Science.gov (United States)

    Iennaco, Joanne DeSanto; Whittemore, Robin; Dixon, Jane

    2017-09-01

    The aim of this study was to identify aggressive event incidence rates in the inpatient psychiatric setting, describe characteristics of events and differences based on aggression target and type (verbal vs. physical). A longitudinal study was carried out of aggressive events identified by workers in four inpatient psychiatric units using the Staff Observation of Aggression Scale-Revised (SOAS-R) over 6 weeks. A total of 113 aggressive events were recorded resulting in a rate of 13.27 events per bed per year. Verbal aggression was demonstrated in 86 % and physical aggression in 57 % of events. Most events (70.8 %, n = 81) targeted a worker. Compared to other targets, workers were 3.4 times more likely to feel threatened (95 % CI 1.2-9.6, χ 2  = 5.08, p = 0.0242), and less likely to have a visible injury (OR 0.15, 95 % CI 0.04-0.6; χ 2  = 7.1, p = 0.0078). Event severity ranged from 0 to 21 with a mean of 9.5(SD = 5.1), with 20 % considered severe. Verbal events had lower mean severity of 6.5(SD = 3.8) versus physical events with a severity of 11.8(SD = 4.8; t = 6.5, df = 111, p Aggression incidence was similar to incidence found in other studies. Workers were the target of most aggressive events and many were identified as having no understandable provocation. Further understanding of event characteristics will promote more effective prevention and management of aggressive events.

  2. Human-directed aggression in the cat.

    Science.gov (United States)

    Curtis, Terry Marie

    2008-09-01

    Feline aggression-between cats or directed at humans-is, after inappropriate elimination and urine-marking behaviors, the second most common reason cats are seen by behavioral specialists. For diagnosis and treatment it is important to determine the motivation for the aggression. The more common causes for human-directed aggression in cats include play, fear, petting intolerance, and redirected aggression. Other causes include pain and maternal behavior. Sexually motivated and status related aggression are much more rare. Treatment includes a combination of behavioral modification, environmental modification, and, in some cases, medication.

  3. Is aggressive treatment of traumatic brain injury cost-effective?

    Science.gov (United States)

    Whitmore, Robert G; Thawani, Jayesh P; Grady, M Sean; Levine, Joshua M; Sanborn, Matthew R; Stein, Sherman C

    2012-05-01

    The object of this study was to determine whether aggressive treatment of severe traumatic brain injury (TBI), including invasive intracranial monitoring and decompressive craniectomy, is cost-effective. A decision-analytical model was created to compare costs, outcomes, and cost-effectiveness of 3 strategies for treating a patient with severe TBI. The aggressive-care approach is compared with "routine care," in which Brain Trauma Foundation guidelines are not followed. A "comfort care" category, in which a single day in the ICU is followed by routine floor care, is included for comparison only. Probabilities of each treatment resulting in various Glasgow Outcome Scale (GOS) scores were obtained from the literature. The GOS scores were converted to quality-adjusted life years (QALYs), based on expected longevity and calculated quality of life associated with each GOS category. Estimated direct (acute and long-term medical care) and indirect (loss of productivity) costs were calculated from the perspective of society. Sensitivity analyses employed a 2D Monte Carlo simulation of 1000 trials, each with 1000 patients. The model was also used to estimate these values for patients 40, 60, and 80 years of age. For the average 20-year-old, aggressive care yields 11.7 (± 1.6 [SD]) QALYs, compared with routine care (10.0 ± 1.5 QALYs). This difference is highly significant (p care remains significantly better at all ages. When all costs are considered, aggressive care is also significantly less costly than routine care ($1,264,000 ± $118,000 vs $1,361,000 ± $107,000) for the average 20-year-old. Aggressive care remains significantly less costly until age 80, at which age it costs more than routine care. However, even in the 80-year-old, aggressive care is likely the more cost-effective approach. Comfort care is associated with poorer outcomes at all ages and with higher costs for all groups except 80-year-olds. When all the costs of severe TBI are considered, aggressive

  4. Increased severity of suicidal behavior in impulsive aggressive patients exposed to familial adversities.

    Science.gov (United States)

    Lopez-Castroman, J; Jaussent, I; Beziat, S; Guillaume, S; Baca-Garcia, E; Genty, C; Olié, E; Courtet, P

    2014-10-01

    The mechanisms by which childhood abuse and family history of suicidal behavior (FHS) lead to an increased risk of suicidal behavior are still unknown. Impulsive aggression may play an intermediate role. We investigated whether greater scores for aggression and impulsivity might be associated with the effects of FHS and/or childhood abuse on the severity of suicidal behavior. We examined the scores of three scales measuring impulsive aggression in a sample of 696 suicide attempters. We compared the highest and lowest scores with regard to reports of childhood abuse and FHS using adjusted multinomial regression models. Genetic polymorphisms of the serotonergic system known to be associated with impulsive aggression were also analyzed. Patients with high impulsive aggressive scores showed significant differences in sociodemographic, clinical and suicidal features compared with patients with low impulsive aggressive scores. Adjusted results showed that combinations of some types of childhood abuse and FHS, particularly emotional abuse and emotional neglect, are associated with high impulsivity and hostility scores. The SS genotype of the serotonin transporter gene (5-HTTLPR) was associated with high levels of impulsivity when the subjects reported emotional abuse [odds ratio (OR) 5.55, 95% confidence interval (CI) 1.75-17.5] or physical abuse (OR 5.03, 95% CI 1.50-16.9) in their childhood. Our results support the role of impulsive aggression as one of the links that may connect childhood abuse and FHS with severity of suicidal behavior.

  5. Thrombomodulin expression regulates tumorigenesis in bladder cancer

    International Nuclear Information System (INIS)

    Wu, Chun-Te; Chang, Ying-Hsu; Lin, Paul- Yang; Chen, Wen-Cheng; Chen, Miao-Fen

    2014-01-01

    The identification of potential tumor markers will help improve therapeutic planning and patient management. Thrombomodulin (TM) is a sensitive urothelial marker. TM was reported to be one of the endogenous anti-metastatic factors and has diagnostic and prognostic values for the progression of carcinoma. In the present study, we examine the role of TM in bladder cancer. We studied the role of TM in tumor behavior and related signaling pathways in vitro using the human bladder cancer cell lines HT1376, HT1197, J82 and T24, and in vivo using animal models. We also selected clinical specimens from 100 patients with bladder cancer for immunohistochemical staining to evaluate the predictive capacity of TM in tumor invasiveness. The data revealed that positive immunoreactivity for TM was inversely correlated with clinical stage and DNA methyltransferase 1 immunoreactivity. Decreased TM expression could predict the aggressive tumor growth and advanced clinical stage in bladder cancer. When TM was inhibited, tumor growth rate and invasion ability were augmented in vitro and in vivo. The underlying changes included increased cell proliferation, enhanced epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, inhibition of NF-κB activation significantly increased TM expression and attenuated tumor aggressiveness in bladder cancer. TM plays an important role in bladder cancer tumor aggressiveness in vitro and in vivo and is a clinically significant predictor that may represent a suitable therapeutic target for bladder cancer

  6. Current questions in HIV-associated lung cancer.

    Science.gov (United States)

    Shcherba, Marina; Shuter, Jonathan; Haigentz, Missak

    2013-09-01

    In this review, we explore current questions regarding risk factors contributing to frequent and early onset of lung cancer among populations with HIV infection, treatment, and outcomes of lung cancer in HIV-infected patients as well as challenges in a newly evolving era of lung cancer screening. Lung cancer, seen in three-fold excess in HIV-infected populations, has become the most common non-AIDS defining malignancy in the highly active antiretroviral therapy era. HIV-associated lung cancer appears to be associated with young age at diagnosis, cigarette smoking, advanced stage at presentation, and a more aggressive clinical course. There is no unified explanation for these observations, and aside from traditional risk factors, HIV-related immunosuppression and biological differences might play a role. In addition to smoking cessation interventions, screening and early cancer detection in HIV-infected populations are of high clinical importance, although evidence supporting lung cancer screening in this particularly high-risk subset is currently lacking, as are prospective studies of lung cancer therapy. There is an urgent need for prospective clinical trials in HIV-associated lung cancer to improve understanding of lung cancer pathogenesis and to optimize patient care. Several clinical trials are in progress to address questions in cancer biology, screening, and treatment for this significant cause of mortality in persons with HIV infection.

  7. Neurogenetics of aggressive behavior: studies in rodents.

    Science.gov (United States)

    Takahashi, Aki; Miczek, Klaus A

    2014-01-01

    Aggressive behavior is observed in many animal species, such as insects, fish, lizards, frogs, and most mammals including humans. This wide range of conservation underscores the importance of aggressive behavior in the animals' survival and fitness, and the likely heritability of this behavior. Although typical patterns of aggressive behavior differ between species, there are several concordances in the neurobiology of aggression among rodents, primates, and humans. Studies with rodent models may eventually help us to understand the neurogenetic architecture of aggression in humans. However, it is important to recognize the difference between the ecological and ethological significance of aggressive behavior (species-typical aggression) and maladaptive violence (escalated aggression) when applying the findings of aggression research using animal models to human or veterinary medicine. Well-studied rodent models for aggressive behavior in the laboratory setting include the mouse (Mus musculus), rat (Rattus norvegicus), hamster (Mesocricetus auratus), and prairie vole (Microtus ochrogaster). The neural circuits of rodent aggression have been gradually elucidated by several techniques, e.g., immunohistochemistry of immediate-early gene (c-Fos) expression, intracranial drug microinjection, in vivo microdialysis, and optogenetics techniques. Also, evidence accumulated from the analysis of gene-knockout mice shows the involvement of several genes in aggression. Here, we review the brain circuits that have been implicated in aggression, such as the hypothalamus, prefrontal cortex (PFC), dorsal raphe nucleus (DRN), nucleus accumbens (NAc), and olfactory system. We then discuss the roles of glutamate and γ-aminobutyric acid (GABA), excitatory and inhibitory amino acids in the brain, as well as their receptors, in controlling aggressive behavior, focusing mainly on recent findings. At the end of this chapter, we discuss how genes can be identified that underlie individual

  8. Relational and Overt Aggression in Urban India: Associations with Peer Relations and Best Friends' Aggression

    Science.gov (United States)

    Bowker, Julie C.; Ostrov, Jamie M.; Raja, Radhi

    2012-01-01

    This study explored the associations between relational and overt aggression and social status, and tested whether the peer correlates of aggression vary as a function of best friends' aggression during early adolescence in urban India. One hundred and ninety-four young adolescents from primarily middle-to-upper-class families in Surat, India…

  9. [Early sibling aggression in mammals and its hormonal correlates].

    Science.gov (United States)

    Antonevich, A L; Naĭdenko, S V

    2007-01-01

    Early sibling aggression is a widespread phenomenon in birds. Ornithologists distinguish species with "obligate" and "facultative" siblicide. Sibling aggression was described in some mammal species: the domestic pig (Sus scrofa), the spotted hyena (Crocuta crocuta), the Eurasian lynx (Lynx lynx), and the Iberian lynx (L. par-dinus). In all of them, sibling aggression corresponds well with the "facultative" siblicide model in birds. Sibling aggression was observed at the age of 36-64 days in both lynx species. It is usually restricted to a single fight and can change the hierarchical structure and growth rate of the kittens. In the spotted hyena and the domestic pig, the frequency and intensity of aggressive interactions between siblings are strongest during the first days of postnatal ontogeny and then decrease gradually. The newborns of these species are much developed than newborn lynx kittens. Usually adult lynx females, in contrast to hyenas and pigs, try to stop sibling fights. This is probably related to the larger parental investment at the time of the fight in lynxes (a kitten's body weight is about 10% of the mother's) than in pigs (0.5%) and hyenas (1.9%). Sibling aggression in spotted hyenas could be related to the high level of androstenedione and is not related to testosterone concentration. In the Eurasian lynx, female sibs attack their littermates slightly more often than male sibs do, and sibling aggression is not testosterone-dependent. Hormones secreted by the adrenal glands may play an important role in this phenomenon. The data available so far, however, do not positively confirm the presence of hormonal trigger effects in mammal sibling aggression.

  10. Aggression and violence around the world: A model of CLimate, Aggression, and Self-control in Humans (CLASH).

    Science.gov (United States)

    Van Lange, Paul A M; Rinderu, Maria I; Bushman, Brad J

    2017-01-01

    Worldwide there are substantial differences within and between countries in aggression and violence. Although there are various exceptions, a general rule is that aggression and violence increase as one moves closer to the equator, which suggests the important role of climate differences. While this pattern is robust, theoretical explanations for these large differences in aggression and violence within countries and around the world are lacking. Most extant explanations focus on the influence of average temperature as a factor that triggers aggression (The General Aggression Model), or the notion that warm temperature allows for more social interaction situations (Routine Activity Theory) in which aggression is likely to unfold. We propose a new model, CLimate, Aggression, and Self-control in Humans (CLASH), that helps us to understand differences within and between countries in aggression and violence in terms of differences in climate. Lower temperatures, and especially larger degrees of seasonal variation in climate, call for individuals and groups to adopt a slower life history strategy, a greater focus on the future (vs. present), and a stronger focus on self-control. The CLASH model further outlines that slow life strategy, future orientation, and strong self-control are important determinants of inhibiting aggression and violence. We also discuss how CLASH differs from other recently developed models that emphasize climate differences for understanding conflict. We conclude by discussing the theoretical and societal importance of climate in shaping individual and societal differences in aggression and violence.

  11. Irradiated riboflavin diminishes the aggressiveness of melanoma in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Daisy Machado

    Full Text Available Melanoma is one of the most aggressive skin cancers due to its high capacity to metastasize. Treatment of metastatic melanomas is challenging for clinicians, as most therapeutic agents have failed to demonstrate improved survival. Thus, new candidates with antimetastatic activity are much needed. Riboavin (RF is a component of the vitamin B complex and a potent photosensitizer. Previously, our group showed that the RF photoproducts (iRF have potential as an antitumoral agent. Hence, we investigated the capacity of iRF on modulating melanoma B16F10 cells aggressiveness in vitro and in vivo. iRF decreases B16F10 cells survival by inhibiting mTOR as well as Src kinase. Moreover, melanoma cell migration was disrupted after treatment with iRF, mainly by inhibition of metalloproteinase (MMP activity and expression, and by increasing TIMP expression. Interestingly, we observed that the Hedgehog (HH pathway was inhibited by iRF. Two mediators of HH signaling, GLI1 and PTCH, were downregulated, while SUFU expression (an inhibitor of this cascade was enhanced. Furthermore, inhibition of HH pathway signaling by cyclopamine and Gant 61 potentiated the antiproliferative action of RF. Accordingly, when a HH ligand was applied, the effect of iRF was almost completely abrogated. Our findings indicate that Hedgehog pathway is involved on the modulation of melanoma cell aggressiveness by iRF. Moreover, iRF treatment decreased pulmonary tumor formation in a murine experimental metastasis model. Research to clarify the molecular action of flavins, in vivo, is currently in progress. Taken together, the present data provides evidence that riboflavin photoproducts may provide potential candidates for improving the efficiency of melanoma treatment.

  12. Aggressive and acute periodontal diseases.

    Science.gov (United States)

    Albandar, Jasim M

    2014-06-01

    Inflammatory periodontal diseases are highly prevalent, although most of these diseases develop and progress slowly, often unnoticed by the affected individual. However, a subgroup of these diseases include aggressive and acute forms that have a relatively low prevalence but show a rapid-course, high rate of progression leading to severe destruction of the periodontal tissues, or cause systemic symptoms that often require urgent attention from healthcare providers. Aggressive periodontitis is an early-onset, destructive disease that shows a high rate of periodontal progression and distinctive clinical features. A contemporary case definition of this disease is presented. Population studies show that the disease is more prevalent in certain geographic regions and ethnic groups. Aggressive periodontitis is an infectious disease, and recent data show that in affected subjects the subgingival microbiota is composed of a mixed microbial infection, with a wide heterogeneity in the types and proportions of microorganisms recovered. Furthermore, there are significant differences in the microbiota of the disease among different geographic regions and ethnicities. There is also evidence that the Aggregatibacter actinomycetemycomitans-JP2 clone may play an important role in the development of the disease in certain populations. The host response plays an important role in the susceptibility to aggressive periodontitis, where the immune response may be complex and involve multiple mechanisms. Also, genetic factors seem to play an important role in the pathogenesis of this disease, but the mechanisms of increased susceptibility are complex and not yet fully understood. The available data suggest that aggressive periodontitis is caused by mutations either in a few major genes or in multiple small-effect genes, and there is also evidence of gene-gene and gene-environment interaction effects. Diagnostic methods for this disease, based on a specific microbiologic, immunologic or

  13. Molecular Subtyping of Serous Ovarian Tumors Reveals Multiple Connections to Intrinsic Breast Cancer Subtypes

    DEFF Research Database (Denmark)

    Jönsson, Jenny-Maria; Johansson, Ida; Dominguez-Valentin, Mev

    2014-01-01

    expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal...

  14. The Role of the School Environment in Relational Aggression and Victimization

    Science.gov (United States)

    Elsaesser, Caitlin; Gorman-Smith, Deborah; Henry, David

    2013-01-01

    Research conducted over the last decade has documented both the high rates of and serious consequences associated with both victimization and perpetration of relational aggression. This study examines risk for involvement in relational aggression and victimization among middle school youth, evaluating both individual beliefs about violence, as…

  15. Facial attractiveness as a moderator of the association between social and physical aggression and popularity in adolescents.

    Science.gov (United States)

    Rosen, Lisa H; Underwood, Marion K

    2010-08-01

    This study examined the relations between facial attractiveness, aggression, and popularity in adolescence to determine whether facial attractiveness would buffer against the negative effects of aggression on popularity. We collected ratings of facial attractiveness from standardized photographs, and teachers provided information on adolescents' social aggression, physical aggression, and popularity for 143 seventh graders (70 girls). Regression analyses indicated that facial attractiveness moderated the relations between both types of aggression and popularity. Aggression was associated with a reduction in popularity for adolescents low on facial attractiveness. However, popularity did not decrease as a function of aggression for adolescents high on facial attractiveness. Aggressors with high facial attractiveness may experience fewer negative consequences to their social standing, thus contributing to higher overall rates of aggression in school settings. Copyright 2010 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

  16. Peculiarities of destructive influence of mass media and fiction on formation of aggressive behaviour of senior pupils

    Directory of Open Access Journals (Sweden)

    Roksoliana Zozuliak-Sluchyk

    2018-01-01

    Full Text Available The article analyzes the media as a factor in the formation of aggressive behavior and propensity to violence seniors. The features of fiction influence the aggressiveness and hostility among high school students. Keywords: aggressive behavior, media, works of fiction, high school, hostility.

  17. Understanding aggressive behaviour across the lifespan.

    Science.gov (United States)

    Liu, J; Lewis, G; Evans, L

    2013-03-01

    Aggressive behaviour is the observable manifestation of aggression and is often associated with developmental transitions and a range of medical and psychiatric diagnoses across the lifespan. As healthcare professionals involved in the medical and psychosocial care of patients from birth through death, nurses frequently encounter - and may serve as - both victims and perpetrators of aggressive behaviour in the workplace. While the nursing literature has continually reported research on prevention and treatment approaches, less emphasis has been given to understanding the aetiology, including contextual precipitants of aggressive behaviour. This paper provides a brief review of the biological, social and environmental risk factors that purportedly give rise to aggressive behaviour. Further, many researchers have focused specifically on aggressive behaviour in adolescence and adulthood. Less attention has been given to understanding the aetiology of such behaviour in young children and older adults. This paper emphasizes the unique risk factors for aggressive behaviour across the developmental spectrum, including childhood, adolescence, adulthood and late life. Appreciation of the risk factors of aggressive behaviour, and, in particular, how they relate to age-specific manifestations, can aid nurses in better design and implementation of prevention and treatment programmes. © 2012 Blackwell Publishing.

  18. IL-1β produced by aggressive breast cancer cells is one of the factors that dictate their interactions with mesenchymal stem cells through chemokine production

    Science.gov (United States)

    Serret, Julien; Bièche, Ivan; Brigitte, Madly; Caicedo, Andres; Sanchez, Elodie; Vacher, Sophie; Vignais, Marie-Luce; Bourin, Philippe; Geneviève, David; Molina, Franck; Jorgensen, Christian; Lazennec, Gwendal

    2015-01-01

    The aim of this work was to understand whether the nature of breast cancer cells could modify the nature of the dialog of mesenchymal stem cells (MSCs) with cancer cells. By treating MSCs with the conditioned medium of metastatic Estrogen-receptor (ER)-negative MDA-MB-231, or non-metastatic ER-positive MCF-7 breast cancer cells, we observed that a number of chemokines were produced at higher levels by MSCs treated with MDA-MB-231 conditioned medium (CM). MDA-MB-231 cells were able to induce NF-κB signaling in MSC cells. This was shown by the use of a NF-kB chemical inhibitor or an IκB dominant negative mutant, nuclear translocation of p65 and induction of NF-κB signature. Our results suggest that MDA-MB-231 cells exert their effects on MSCs through the secretion of IL-1β, that activates MSCs and induces the same chemokines as the MDA-MB-231CM. In addition, inhibition of IL-1β secretion in the MDA-MB-231 cells reduces the induced production of a panel of chemokines by MSCs, as well the motility of MDA-MB-231 cells. Our data suggest that aggressive breast cancer cells secrete IL-1β, which increases the production of chemokines by MSCs. PMID:26362269

  19. Novel Biophysical Marker of Aggressive Prostate Cancer Cells

    Science.gov (United States)

    2013-06-01

    756 30.33 PrEC LHSR 8.60 687 19.71 PC-3 9.31 744 48.42 TEM 4–18 8.55 683 45.00 22Rv1 7.27 581 41.00 MD.MBA.231 8.16 652 32.43 B16.f0 9.11 728 37.37 Panc ...established human cancer cell lines evaluated, PANC -1 pancreatic cancer cells and Jurkat leukemia cells, were considerably more sensitive to the FSS

  20. Developmental Trajectories of Peer-Reported Aggressive Behavior: The Role of Friendship Understanding, Friendship Quality, and Friends' Aggressive Behavior.

    Science.gov (United States)

    Malti, Tina; McDonald, Kristina; Rubin, Kenneth H; Rose-Krasnor, Linda; Booth-LaForce, Cathryn

    2015-10-01

    To investigate developmental trajectories in peer-reported aggressive behavior across the transition from elementary-to-middle school, and whether aggressive behavior trajectories were associated with friendship quality, friends' aggressive behavior, and the ways in which children think about their friendships. Participants included a community sample of 230 5 th grade children who were assessed when they made a transition from elementary-to-middle school (6 th grade). Peer nominations were used to assess the target child's and friend's aggressive behavior. Self- and friend reports were used to measure friendship quality; friendship understanding was assessed via a structured interview. General Growth Mixture Modeling (GGMM) revealed three distinct trajectories of peer-reported aggressive behavior across the school transition: low-stable, decreasing, and increasing. Adolescents' understanding of friendship formation differentiated the decreasing from the low-stable aggressive behavior trajectories, and the understanding of friendship trust differentiated the increasing from the low-stable aggressive and decreasing aggressive behavior trajectories. The findings indicated that a sophisticated understanding of friendship may serve as a protective factor for initially aggressive adolescents as they transition into middle school. Promoting a deepened understanding of friendship relations and their role in one's own and others' well-being may serve as an important prevention and intervention strategy to reduce aggressive behavior.

  1. Radical prostatectomy for high-risk prostate cancer.

    Science.gov (United States)

    Yossepowitch, Ofer; Eastham, James A

    2008-06-01

    Consensus recommendations for the identification and treatment of men whose apparent organ confined prostate cancer has high risk features are lacking. Despite ongoing refinements in surgical technique and improvements in morbidity and functional outcomes, the tradition of steering high-risk patients away from radical prostatectomy (RP) remains steadfast. We performed a medical literature search in English using MEDLINE/PubMed that addressed high risk prostate cancer. We analyzed the literature with respect to the historical evolution of this concept, current risk stratification schemes and treatment guidelines and related short and long term outcomes following RP. Contemporary evidence suggest that patients classified with high-risk prostate cancer by commonly used definitions do not have a uniformly poor prognosis after RP. Many cancers categorized clinically as high risk are actually pathologically confined to the prostate, and most men with such cancers who undergo RP are alive and free of additional therapy long after surgery. RP in the high-risk setting appears to be associated with a similar morbidity as in lower-risk patients. Men with clinically localized high-risk prostate cancer should not be categorically disqualified from local definitive therapy with RP. With careful attention to surgical technique, cancer control rates should improve further, and adverse effects on quality of life after RP should continue to decrease.

  2. Family predictors of continuity and change in social and physical aggression from ages 9 to 18.

    Science.gov (United States)

    Ehrenreich, Samuel E; Beron, Kurt J; Brinkley, Dawn Y; Underwood, Marion K

    2014-01-01

    This research examined developmental trajectories for social and physical aggression for a sample followed from age 9 to 18, and investigated possible family predictors of following different trajectory groups. Participants were 158 girls and 138 boys, their teachers, and their parents (21% African American, 5.3% Asian, 51.6% Caucasian, and 21% Hispanic). Teachers rated children's social and physical aggression yearly in grades 3-12. Participants' parent (83% mothers) reported on family income, conflict strategies, and maternal authoritarian and permissive parenting styles. The results suggested that both social and physical aggression decline slightly from middle childhood through late adolescence. Using a dual trajectory model, group-based mixture modeling revealed three trajectory groups for both social and physical aggression: low-, medium-, and high-desisting for social aggression, and stably-low, stably-medium, and high-desisting for physical aggression. Membership in higher trajectory groups was predicted by being from a single-parent family, and having a parent high on permissiveness. Being male was related to both elevated physical aggression trajectories and the medium-desisting social aggression trajectory. Negative interparental conflict strategies did not predict social or physical aggression trajectories when permissive parenting was included in the model. Permissive parenting in middle childhood predicted following higher social aggression trajectories across many years, which suggests that parents setting fewer limits on children's behaviors may have lasting consequences for their peer relations. Future research should examine transactional relations between parenting styles and practices and aggression to understand the mechanisms that may contribute to changes in involvement in social and physical aggression across childhood and adolescence. © 2014 Wiley Periodicals, Inc.

  3. Family Predictors of Continuity and Change in Social and Physical Aggression from Ages 9 – 18

    Science.gov (United States)

    Ehrenreich, Samuel E.; Beron, Kurt J.; Brinkley, Dawn Y.; Underwood, Marion K.

    2014-01-01

    This research examined developmental trajectories for social and physical aggression for a sample followed from age 9–18, and investigated possible family predictors of following different trajectory groups. Participants were 158 girls and 138 boys, their teachers, and their parents (21% African American, 5.3% Asian, 51.6% Caucasian, and 21% Hispanic). Teachers rated children’s social and physical aggression yearly in grades 3–12. Participants’ parent (83% mothers) reported on family income, conflict strategies, and maternal authoritarian and permissive parenting styles. The results suggested that both social and physical aggression decline slightly from middle childhood through late adolescence. Using a dual trajectory model, group based mixture modeling revealed three trajectory groups for both social and physical aggression: low-, medium-, and high-desisting for social aggression, and stably-low, stably-medium, and high-desisting for physical aggression. Membership in higher trajectory groups was predicted by being from a single-parent family, and having a parent high on permissiveness. Being male was related to both elevated physical aggression trajectories and the medium-desisting social aggression trajectory. Negative interparental conflict strategies did not predict social or physical aggression trajectories when permissive parenting was included in the model. Permissive parenting in middle childhood predicted following higher social aggression trajectories across many years, which suggests that parents setting fewer limits on children’s behaviors may have lasting consequences for their peer relations. Future research should examine transactional relations between parenting styles and practices and aggression to understand the mechanisms that may contribute to changes in involvement in social and physical aggression across childhood and adolescence. PMID:24888340

  4. Influence of school-level and family-level variables on Chinese college students' aggression.

    Science.gov (United States)

    Zhou, Jiawei; Yang, Jiarun; Yu, Yunmiao; Wang, Lin; Han, Dong; Zhu, Xiongzhao; He, Jincai; Qiu, Xiaohui; Yang, Xiuxian; Qiao, Zhengxue; Sui, Hong; Yang, Yanjie

    2017-08-01

    With the frequent occurrence of campus violence, scholars have devoted increasing attention to college students' aggression. This study aims to estimate the prevalence of aggression in Chinese university students and identify factors that could influence their aggression. We can thus find methods to reduce the incidence of college students' aggression in the future. A multi-stage stratified sampling procedure was used to select university students (N = 4565) aged 16-25 years in Harbin. The Aggression Questionnaire, the Adolescent Self-Rating Life Events Checklist and the Social Support Revalued Scale were used to collect data. Females reported lower levels of aggression than males (p aggression, and the model was highly significant (R 2  = .233, Ad R 2  = .230, p aggression is affected by gender, family-level and school-level variables. Aggression scores are significantly correlated with not only family-level or school-level variables independently, but their combination as well. We find that the risk factors for aggression include a dissatisfying profession, higher levels of study pressure, poor parental relationships, poor interpersonal relationships, the presence of siblings, punishment, health maladjustment, less subjective support, and lower levels of utilization of social support.

  5. Lithium in the treatment of aggression.

    Science.gov (United States)

    Sheard, M H

    1975-02-01

    Lithium has become a widely accepted treatment for manic-depressive psychosis. It is dramatically effective for many cases of mania and is useful in the prevention of manic and depressive episodes. Hyperaggressiveness and hypersexuality are frequent components of manic-depressive illness and abate under the influence of lithium. A brief review is presented of the behavioral and biochemical pharmacology of lithium. This documents the inhibitory role which lithium can play in several examples of animal aggressive behavior including pain-elicited aggression, mouse killing in rats, isolation-induced aggression in mice, p-chlorophenylalanine-induced aggression in rats, and hypothalamically induced aggression in cats. The use of lithium to control human aggressive behavior has resulted in controversial findings. In epileptic conditions, improvement has been reported in interseizure aggressivity, but other reports indicate the possibility of increased seizures. Improvement in aggressive behavior in childhood has occasionally been reported as well as in emotionally unstable character disorders in young female patients. Te was a single blind study and the other a large but uncontrolled study. Both studies reported an improvement in aggressiveness as indicated by fewer recorded reports (tickets) for fighting. The final study reported is a study of 12 male delinquents age 16 to 23. They received lithium or placebo for 4 months inside an institution and then a trial of lithium for 1 to 12 months on an outpatient basis. Analysis of results in terms of the number of aggressive antisocial acts showed fewer serious aggressive episodes when the lithium level was between 0.6 and 1 meq/liter than when it was between 0.0 and 0.6 meq/liter. These results must be viewed with caution and are only suggestive since the study was not double blind.

  6. Imaging the neural circuitry and chemical control of aggressive motivation

    Directory of Open Access Journals (Sweden)

    Blanchard D Caroline

    2008-11-01

    Full Text Available Abstract Background With the advent of functional magnetic resonance imaging (fMRI in awake animals it is possible to resolve patterns of neuronal activity across the entire brain with high spatial and temporal resolution. Synchronized changes in neuronal activity across multiple brain areas can be viewed as functional neuroanatomical circuits coordinating the thoughts, memories and emotions for particular behaviors. To this end, fMRI in conscious rats combined with 3D computational analysis was used to identifying the putative distributed neural circuit involved in aggressive motivation and how this circuit is affected by drugs that block aggressive behavior. Results To trigger aggressive motivation, male rats were presented with their female cage mate plus a novel male intruder in the bore of the magnet during image acquisition. As expected, brain areas previously identified as critical in the organization and expression of aggressive behavior were activated, e.g., lateral hypothalamus, medial basal amygdala. Unexpected was the intense activation of the forebrain cortex and anterior thalamic nuclei. Oral administration of a selective vasopressin V1a receptor antagonist SRX251 or the selective serotonin reuptake inhibitor fluoxetine, drugs that block aggressive behavior, both caused a general suppression of the distributed neural circuit involved in aggressive motivation. However, the effect of SRX251, but not fluoxetine, was specific to aggression as brain activation in response to a novel sexually receptive female was unaffected. Conclusion The putative neural circuit of aggressive motivation identified with fMRI includes neural substrates contributing to emotional expression (i.e. cortical and medial amygdala, BNST, lateral hypothalamus, emotional experience (i.e. hippocampus, forebrain cortex, anterior cingulate, retrosplenial cortex and the anterior thalamic nuclei that bridge the motor and cognitive components of aggressive responding

  7. Variables Related to Attitudes toward Domestic Violence and Use of Reasoning, Verbal Aggression, and Violent Conflict Tactics in High School Students.

    Science.gov (United States)

    Jones, Shannon R.; Gardner, Scott P.

    2002-01-01

    A study of 122 high school students investigated how gender, self-esteem, attitudes toward cohabitation, family openness, parents' annual income, and race were related to attitude towards dating violence. More family openness correlated with use of reasoning in dating conflicts. Low self-esteem correlated with high verbal aggression. (Contains 67…

  8. When violence pays: a cost-benefit analysis of aggressive behavior in animals and humans.

    Science.gov (United States)

    Georgiev, Alexander V; Klimczuk, Amanda C E; Traficonte, Daniel M; Maestripieri, Dario

    2013-07-18

    An optimization analysis of human behavior from a comparative perspective can improve our understanding of the adaptiveness of human nature. Intra-specific competition for resources provides the main selective pressure for the evolution of violent aggression toward conspecifics, and variation in the fitness benefits and costs of aggression can account for inter-specific and inter-individual differences in aggressiveness. When aggression reflects competition for resources, its benefits vary in relation to the characteristics of the resources (their intrinsic value, abundance, spatial distribution, and controllability) while its costs vary in relation to the characteristics of organisms and how they fight (which, in turn, affects the extent to which aggression entails risk of physical injury or death, energetic depletion, exposure to predation, psychological and physiological stress, or damage to social relationships). Humans are a highly aggressive species in comparison to other animals, probably as a result of an unusually high benefit-to-cost ratio for intra-specific aggression. This conclusion is supported by frequent and widespread occurrence of male-male coalitionary killing and by male-female sexual coercion. Sex differences in violent aggression in humans and other species probably evolved by sexual selection and reflect different optimal competitive strategies for males and females.

  9. When Violence Pays: A Cost-Benefit Analysis of Aggressive Behavior in Animals and Humans

    Directory of Open Access Journals (Sweden)

    Alexander V. Georgiev

    2013-07-01

    Full Text Available An optimization analysis of human behavior from a comparative perspective can improve our understanding of the adaptiveness of human nature. Intra-specific competition for resources provides the main selective pressure for the evolution of violent aggression toward conspecifics, and variation in the fitness benefits and costs of aggression can account for inter-specific and inter-individual differences in aggressiveness. When aggression reflects competition for resources, its benefits vary in relation to the characteristics of the resources (their intrinsic value, abundance, spatial distribution, and controllability while its costs vary in relation to the characteristics of organisms and how they fight (which, in turn, affects the extent to which aggression entails risk of physical injury or death, energetic depletion, exposure to predation, psychological and physiological stress, or damage to social relationships. Humans are a highly aggressive species in comparison to other animals, probably as a result of an unusually high benefit-to-cost ratio for intra-specific aggression. This conclusion is supported by frequent and widespread occurrence of male-male coalitionary killing and by male-female sexual coercion. Sex differences in violent aggression in humans and other species probably evolved by sexual selection and reflect different optimal competitive strategies for males and females.

  10. Aggressive effects of prioritizing popularity in early adolescence.

    Science.gov (United States)

    Cillessen, Antonius H N; Mayeux, Lara; Ha, Thao; de Bruyn, Eddy H; LaFontana, Kathryn M

    2014-01-01

    This study examined the moderating effects of prioritizing popularity on the association between early adolescents' popularity and their aggressive, leadership, and prosocial behaviors with peers. Participants were 288 14-year-olds from The Netherlands who completed a sociometric instrument and an assessment of how much they prioritized popularity over other personal goals. Results indicated that prioritizing popularity was distinct from actual popularity in the peer group. Further, prioritizing popularity moderated the association of popularity with aggressive and leadership behaviors, with adolescents who were both popular and who prioritized popularity being particularly aggressive and scoring high on leadership behaviors. This trend was especially true for boys. The same moderating effect was not found for prosocial behaviors. Motivational and social-cognitive factors in the dynamics of peer popularity are highlighted. © 2013 Wiley Periodicals, Inc.

  11. Aggressive angiomyxoma with diffusion-weighted magnetic resonance imaging and dynamic contrast enhancement: a case report and review of the literature.

    Science.gov (United States)

    Brunelle, S; Bertucci, F; Chetaille, B; Lelong, B; Piana, G; Sarran, A

    2013-05-01

    Aggressive angiomyxoma (AA) is a rare benign soft tissue tumour usually affecting the pelvis and perineum of young women. Magnetic resonance imaging (MRI) is crucial in the management of AA patients for its diagnostic contribution and for the preoperative assessment of the actual tumour extension. Given the current development of less aggressive therapeutics associated with a higher risk of recurrence, close follow-up with MRI is fundamental after treatment. In this context, diffusion-weighted (DW) imaging has already shown high efficacy in the detection of early small relapses in prostate or rectal cancer. We report here a case of pelvic AA in a 51-year-old woman examined with dynamic contrast enhancement and DW-MRI, including apparent diffusion coefficient mapping and calculation. To our knowledge, this is the first description of DW-MRI in AA reported in the literature. Here, knowledge about imaging features of AA will be reviewed and expanded.

  12. Sleep deprivation suppresses aggression in Drosophila

    Science.gov (United States)

    Kayser, Matthew S; Mainwaring, Benjamin; Yue, Zhifeng; Sehgal, Amita

    2015-01-01

    Sleep disturbances negatively impact numerous functions and have been linked to aggression and violence. However, a clear effect of sleep deprivation on aggressive behaviors remains unclear. We find that acute sleep deprivation profoundly suppresses aggressive behaviors in the fruit fly, while other social behaviors are unaffected. This suppression is recovered following post-deprivation sleep rebound, and occurs regardless of the approach to achieve sleep loss. Genetic and pharmacologic approaches suggest octopamine signaling transmits changes in aggression upon sleep deprivation, and reduced aggression places sleep-deprived flies at a competitive disadvantage for obtaining a reproductive partner. These findings demonstrate an interaction between two phylogenetically conserved behaviors, and suggest that previous sleep experiences strongly modulate aggression with consequences for reproductive fitness. DOI: http://dx.doi.org/10.7554/eLife.07643.001 PMID:26216041

  13. Aggressiveness, violence, homicidality, homicide, and Lyme disease

    Directory of Open Access Journals (Sweden)

    Bransfield RC

    2018-03-01

    Full Text Available Robert C Bransfield Department of Psychiatry, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ, USA Background: No study has previously analyzed aggressiveness, homicide, and Lyme disease (LD. Materials and methods: Retrospective LD chart reviews analyzed aggressiveness, compared 50 homicidal with 50 non-homicidal patients, and analyzed homicides. Results: Most aggression with LD was impulsive, sometimes provoked by intrusive symptoms, sensory stimulation or frustration and was invariably bizarre and senseless. About 9.6% of LD patients were homicidal with the average diagnosis delay of 9 years. Postinfection findings associated with homicidality that separated from the non-homicidal group within the 95% confidence interval included suicidality, sudden abrupt mood swings, explosive anger, paranoia, anhedonia, hypervigilance, exaggerated startle, disinhibition, nightmares, depersonalization, intrusive aggressive images, dissociative episodes, derealization, intrusive sexual images, marital/family problems, legal problems, substance abuse, depression, panic disorder, memory impairments, neuropathy, cranial nerve symptoms, and decreased libido. Seven LD homicides included predatory aggression, poor impulse control, and psychosis. Some patients have selective hyperacusis to mouth sounds, which I propose may be the result of brain dysfunction causing a disinhibition of a primitive fear of oral predation.Conclusion: LD and the immune, biochemical, neurotransmitter, and the neural circuit reactions to it can cause impairments associated with violence. Many LD patients have no aggressiveness tendencies or only mild degrees of low frustration tolerance and irritability and pose no danger; however, a lesser number experience explosive anger, a lesser number experience homicidal thoughts and impulses, and much lesser number commit homicides. Since such large numbers are affected by LD, this small percent can be highly significant. Much of the

  14. Behavioral aggressiveness in boys with sexual precocity

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    Bindu Kulshreshtha

    2012-01-01

    Full Text Available Background: Some boys with sexual precocity are known to have behavioral problems like increased physical and verbal aggression and school and social maladjustments. It is believed to be due to premature androgen exposure. However, it is not clear why only some develop this problem, difference in etiology could be one explanation. Aim: The aim of the study is to assess behavioral aggression in boys with sexual precocity due to different disorders. Materials and Methods: Seven children, ages three to seven years, were enrolled for this study. Two were diagnosed to have congenital adrenal hyperplasia (CAH, three had testotoxicosis, while two had central precocious puberty. Parents of children with precocious puberty underwent the (CASP questionnaire (children′s aggression scale-parent version. Results: Testosterone levels were high in all patients. Parents denied any history of physical or verbal aggression in the two boys with CAH. Their CASP rating was 0. In contrast, the CASP ratings in the two boys with testotoxicosis and the two with precocious puberty for five domains ranged from 3.1 - 24.2, 2.6 - 8.3,1-5.6,0 - 7.1, and 0 - 1, respectively. In the present study, increased aggression was seen among all the patients with testotoxicosis and both with precocious puberty. In contrast, there were no symptoms of either increased verbal or physical aggression in either of the two patients with CAH. Conclusions: The hormonal milieu in the boys with CAH versus those with sexual precocity due to other causes differed in terms of cortisol and androgen precursors. The androgen excess in CAH children was a consequence of cortisol deficiency. It is possible that cortisol sufficiency is required for androgen-mediated behavioral effects.

  15. Manipulation of colony environment modulates honey bee aggression and brain gene expression.

    Science.gov (United States)

    Rittschof, C C; Robinson, G E

    2013-11-01

    The social environment plays an essential role in shaping behavior for most animals. Social effects on behavior are often linked to changes in brain gene expression. In the honey bee (Apis mellifera L.), social modulation of individual aggression allows colonies to adjust the intensity with which they defend their hive in response to predation threat. Previous research has showed social effects on both aggression and aggression-related brain gene expression in honey bees, caused by alarm pheromone and unknown factors related to colony genotype. For example, some bees from less aggressive genetic stock reared in colonies with genetic predispositions toward increased aggression show both increased aggression and more aggressive-like brain gene expression profiles. We tested the hypothesis that exposure to a colony environment influenced by high levels of predation threat results in increased aggression and aggressive-like gene expression patterns in individual bees. We assessed gene expression using four marker genes. Experimentally induced predation threats modified behavior, but the effect was opposite of our predictions: disturbed colonies showed decreased aggression. Disturbed colonies also decreased foraging activity, suggesting that they did not habituate to threats; other explanations for this finding are discussed. Bees in disturbed colonies also showed changes in brain gene expression, some of which paralleled behavioral findings. These results show that bee aggression and associated molecular processes are subject to complex social influences. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  16. SU-D-207A-03: Potential Role of BOLD MRI in Discrimination of Aggressive Tumor Habitat in Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ford, J; Lopez, C; Tschudi, Y; Breto, A; Padgett, K; Pollack, A; Stoyanova, R [University of Miami Miller School of Medicine, Miami, FL (United States)

    2016-06-15

    Purpose: To determine whether blood oxygenation level dependent (BOLD) MRI signal measured in prostate cancer patients, in addition to quantitative diffusion and perfusion parameters from multiparametric (mp)MRI exams, can help discriminate aggressive and/or radioresistant lesions. Methods: Several ongoing clinical trials in our institution require mpMRI exam to determine eligibility (presence of identifiable tumor lesion on mpMRI) and prostate volumes for dose escalation. Upon consent, patients undergo fiducial markers placement and a T2*-weighted imaging at the time of CT sim to facilitate the fusion. In a retrospective analysis eleven clinical trial patients were identified who had undergone mpMRI on GE 3T magnet, followed by T2*-weighted imaging (time-period mean±SD = 48±20 days) using a consistent protocol (gradient echo, TR/TE=30/11.8ms, flip angle=12, matrix=256×256×75, voxel size=1.25×1.25×2.5mm). ROIs for prostate tumor lesions were automatically determined using ADC threshold ≤1200 µm2/s. Although the MR protocol was not intended for BOLD analysis, we utilized the T2*-weighted signal normalized to that in nearby muscle; likewise, T2-weighted lesion signal was normalized to muscle, following rigid registration of the T2 to T2* images. The ratio of these normalized signals, T2*/T2, is a measure of BOLD effect in the prostate tumors. Perfusion parameters (Ktrans, ve, kep) were also calculated. Results: T2*/T2 (mean±SE) was found to be substantially lower for Gleason score (GS) 8&9 (0.82±0.04) compared to GS 7 (1.08±0.07). A k-means cluster analysis of T2*/T2 versus kep = Ktrans/ve revealed two distinct clusters, one with higher T2*/T2 and lower kep, containing only GS 7 lesions, and another with lower T2*/T2 and higher kep, associated with tumor aggressiveness. This latter cluster contained all GS 8&9 lesions, as well as some GS 7. Conclusion: BOLD MRI, in addition to ADC and kep, may play a role (perhaps orthogonal to Gleason score) in

  17. DUSP4/MKP2 overexpression is associated with BRAFV600E mutation and aggressive behavior of papillary thyroid cancer

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    Ma B

    2016-04-01

    Full Text Available Ben Ma,1,2,* Rongliang Shi,1–3,* Shuwen Yang,1,2 Li Zhou,1,2 Ning Qu,1,2 Tian Liao,1,2 Yu Wang,1,2 Yulong Wang,1,2 Qinghai Ji1,2 1Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, 2Department of Oncology, Shanghai Medical College, 3Department of General Surgery, Fudan University, Minhang Hospital, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: The study was performed to retrospectively analyze the correlation of dual specificity phosphatase 4 (DUSP4 expression with clinicopathological variables and BRAFV600E mutation to better characterize the potential role of DUSP4 as a biomarker in papillary thyroid cancer (PTC. Patients (n=120 who underwent surgery for PTC at Fudan University Shanghai Cancer Center (FUSCC were enrolled in this study, and a validation cohort from The Cancer Genome Atlas (TCGA database was identified to confirm the preliminary findings in our study. We investigated DUSP4 expression at the mRNA level in PTC tissues and adjacent normal tissues using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR. BRAFV600E mutation analysis was also performed in PTC tissues using Sanger sequencing. Initially, we compared PTC tissues with paired normal tissues in DUSP4 expression using Student’s t-test, and then analyzed the correlation of DUSP4 with clinicopathological variables and BRAFV600E mutation in PTC using Mann–Whitney U, Kruskal–Wallis, χ2, and Fisher’s exact tests. Human-derived thyroid cell lines were also used to verify our findings. DUSP4 was significantly overexpressed in PTC tissues compared with the adjacent normal tissues (P<0.001. High DUSP4 expression showed a significant association with lymph node metastasis and extrathyroidal extension in both FUSCC and TCGA cohorts, and DUSP4 overexpression was an independent risk factor for lymph node metastasis in multivariate analysis. Additionally, DUSP4 expression

  18. Aggressive Erotica and Violence against Women.

    Science.gov (United States)

    Donnerstein, Edward

    1980-01-01

    Examines the effects of aggressive-erotic stimuli on male aggression toward females. Male subjects' deliveries of electric shocks to males or females after viewing either a neutral, erotic, or aggressive-erotic film were measured. (Author/SS)

  19. REMOVING AGGRESSIVE CARBON DIOXIDE FROM WATER USING MELAPHYRE BED

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    Magdalena Maria Michel

    2017-09-01

    Full Text Available The experiment was based on filtration of the highly aggressive water through the melaphyre bed. The quartz bed was non-reactive reference material. The aim of this work was to determine the ability of the melaphyre to remove aggressive CO2 during the chemical reaction. It was noted that a decrease of acidity of the filtrate in comparison to the feed and an increase of its alkalinity and pH. It was calculated that until the moment of exhaustion of the de-acidifying properties of the melaphyre, maximum amount of bound CO2 added to the water was 29.7 g CO2/L of the bed, and maximum amount of the aggressive CO2 removed from the water was 33.3 g CO2/L of the bed. Regarding very high content of the aggressive CO2 (116 mg/L average in the feed only 28.76% of this component was subject to transformation into bound and affiliated CO2 in the filtrate. For the melaphyre bed the CO2 loss from the experiment system following from desorption was 7.80% of the total load of CO2 added with the feed. On the quartz bed the loss was slightly lower 4.56%.

  20. Aggressiveness and intelligence in adolescence

    Directory of Open Access Journals (Sweden)

    Juliana Munique de Souza Siqueira

    2013-02-01

    Full Text Available This study aimed to analyse the aggressiveness and intelligence in adolescence, and to verify if exists association through these variables. The aggressiveness is inherent in human nature and collaborates in the construction of personality by influencing the behaviors positively or negatively. Intelligence refers to the cognitive skill that every individual has and contributes to the establishment of social relations. As a teenager the aggressiveness and the intelligence become more evident due to change in this phase of development. The sample of 35 adolescents of both sexes participated in this survey. The instruments used were the batch of reasoning tests – BPR-5 and the Aggressiveness scale for children and young people. The results indicated that there is no relationship between aggression and intelligence. However, based on the literature these variables interrelate. Therefore, it is suggested that this research be expanded with the use of other psychological instruments.

  1. The perception of aggression

    NARCIS (Netherlands)

    Jansen, G; Dassen, T; Moorer, P

    1997-01-01

    Several academic and clinical disciplines are involved in clarifying the concept of aggression by formulating operational and descriptive definitions. In the present paper the validity of the definitions of aggression, reported by nurses in an earlier qualitative study, is examined, using a survey

  2. Quantitative discrimination of Aggregatibacter actinomycetemcomitans highly leukotoxic JP2 clone from non-JP2 clones in diagnosis of aggressive periodontitis.

    Science.gov (United States)

    Yoshida, Akihiro; Ennibi, Oum-Keltoum; Miyazaki, Hideo; Hoshino, Tomonori; Hayashida, Hideaki; Nishihara, Tatsuji; Awano, Shuji; Ansai, Toshihiro

    2012-10-11

    Aggregatibacter actinomycetemcomitans is the etiological agent of periodontitis, and there is a strong association between clone JP2 and aggressive periodontitis in adolescents of African descent. The JP2 clone has an approximately 530-bp deletion (∆530) in the promoter region of the lkt/ltx gene, which encodes leukotoxin, and this clone has high leukotoxic activity. Therefore, this clone is very important in aggressive periodontitis. To diagnose this disease, culture methods and conventional PCR techniques are used. However, quantitative detection based on qPCR for the JP2 clone has not been developed due to genetic difficulties. In this study, we developed a qPCR-based quantification method specific to the JP2 clone. Based on our analysis of the DNA sequence of the lkt/ltx gene and its flanking region, we designed a reverse primer specific for the ∆530 deletion border sequence and developed a JP2-specific PCR-based quantification method using this primer. We also analyzed the DNA sequence of the ∆530 locus and found it to be highly conserved (97-100%) among 17 non-JP2 strains. Using the ∆530 locus, we designed a qPCR primer-probe set specific to non-JP2 clones. Next, we determined the numbers of JP2 and non-JP2 clone cells in the periodontal pockets of patients with aggressive periodontitis. The JP2-specific primers specifically amplified the genomic DNA of the A. actinomycetemcomitans JP2 clone and did not react with other bacterial DNA, whereas the non-JP2 specific primers reacted only with A. actinomycetemcomitans non-JP2 clones. Samples from the 88 periodontal sites in the 11 patients with aggressive periodontitis were analyzed. The bacterial cell numbers in 88 periodontal sites ranged from 0 to 4.8 × 10(8) (mean 1.28 × 10(7)) for JP2 clones and from 0 to 1.6 × 10(6) for non-JP2 clones (mean 1.84 × 10(5)). There were significant differences in the JP2 cell number between a clinical attachment level (CAL) ≤6 mm and a level ≥7 mm (p clones. This

  3. Exogenous Testosterone Rapidly Increases Aggressive Behavior in Dominant and Impulsive Men.

    Science.gov (United States)

    Carré, Justin M; Geniole, Shawn N; Ortiz, Triana L; Bird, Brian M; Videto, Amber; Bonin, Pierre L

    2017-08-15

    Although traditional wisdom suggests that baseline levels of testosterone (T) promote aggressive behavior, decades of research have produced findings that have been largely weak and inconsistent. However, more recent experimental work suggests that exogenous administration of T rapidly potentiates amygdala and hypothalamus responses to angry facial expressions. Notably, these brain regions are rich in androgen receptors and play a key role in modulating aggressive behavior in animal models. The present experiment extends this work by examining whether acutely increasing T potentiates aggressive behavior in men. In a double-blind, placebo-controlled, between-subject design, healthy adult men (n = 121) were administered either T or placebo, and subsequently engaged in a well-validated decision-making game that measures aggressive behavior in response to social provocation. In light of prior correlational research, we also assessed the extent to which T's effects on aggressive behavior would depend on variability in trait dominance and/or trait self-control. Exogenous T on its own did not modulate aggressive behavior. However, T's effects on aggression were strongly influenced by variation in trait dominance and trait self-control. Specifically, T caused an increase in aggressive behavior, but only among men scoring relatively high in trait dominance or low in trait self-control. These findings are the first to demonstrate that T can rapidly (within 60 minutes) potentiate aggressive behavior, but only among men with dominant or impulsive personality styles. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  4. Developmental Trajectories of Peer-Reported Aggressive Behavior: The Role of Friendship Understanding, Friendship Quality, and Friends’ Aggressive Behavior

    Science.gov (United States)

    Malti, Tina; McDonald, Kristina; Rubin, Kenneth H.; Rose-Krasnor, Linda; Booth-LaForce, Cathryn

    2015-01-01

    Objective To investigate developmental trajectories in peer-reported aggressive behavior across the transition from elementary-to-middle school, and whether aggressive behavior trajectories were associated with friendship quality, friends’ aggressive behavior, and the ways in which children think about their friendships. Method Participants included a community sample of 230 5th grade children who were assessed when they made a transition from elementary-to-middle school (6th grade). Peer nominations were used to assess the target child’s and friend’s aggressive behavior. Self- and friend reports were used to measure friendship quality; friendship understanding was assessed via a structured interview. Results General Growth Mixture Modeling (GGMM) revealed three distinct trajectories of peer-reported aggressive behavior across the school transition: low-stable, decreasing, and increasing. Adolescents’ understanding of friendship formation differentiated the decreasing from the low-stable aggressive behavior trajectories, and the understanding of friendship trust differentiated the increasing from the low-stable aggressive and decreasing aggressive behavior trajectories. Conclusions The findings indicated that a sophisticated understanding of friendship may serve as a protective factor for initially aggressive adolescents as they transition into middle school. Promoting a deepened understanding of friendship relations and their role in one’s own and others’ well-being may serve as an important prevention and intervention strategy to reduce aggressive behavior. PMID:26688775

  5. Predictive and therapeutic markers in ovarian cancer

    Science.gov (United States)

    Gray, Joe W.; Guan, Yinghui; Kuo, Wen-Lin; Fridlyand, Jane; Mills, Gordon B.

    2013-03-26

    Cancer markers may be developed to detect diseases characterized by increased expression of apoptosis-suppressing genes, such as aggressive cancers. Genes in the human chromosomal regions, 8q24, 11q13, 20q11-q13, were found to be amplified indicating in vivo drug resistance in diseases such as ovarian cancer. Diagnosis and assessment of amplification levels certain genes shown to be amplified, including PVT1, can be useful in prediction of poor outcome of patient's response and drug resistance in ovarian cancer patients with low survival rates. Certain genes were found to be high priority therapeutic targets by the identification of recurrent aberrations involving genome sequence, copy number and/or gene expression are associated with reduced survival duration in certain diseases and cancers, specifically ovarian cancer. Therapeutics to inhibit amplification and inhibitors of one of these genes, PVT1, target drug resistance in ovarian cancer patients with low survival rates is described.

  6. Analysis of urinary PSA glycosylation is not indicative of high-risk prostate cancer.

    Science.gov (United States)

    Barrabés, Sílvia; Llop, Esther; Ferrer-Batallé, Montserrat; Ramírez, Manel; Aleixandre, Rosa N; Perry, Antoinette S; de Llorens, Rafael; Peracaula, Rosa

    2017-07-01

    The levels of core fucosylation and α2,3-linked sialic acid in serum Prostate Specific Antigen (PSA), using the lectins Pholiota squarrosa lectin (PhoSL) and Sambucus nigra agglutinin (SNA), can discriminate between Benign Prostatic Hyperplasia (BPH) and indolent prostate cancer (PCa) from aggressive PCa. In the present work we evaluated whether these glycosylation determinants could also be altered in urinary PSA obtained after digital rectal examination (DRE) and could also be useful for diagnosis determinations. For this purpose, α2,6-sialic acid and α1,6-fucose levels of urinary PSA from 53 patients, 18 biopsy-negative and 35 PCa patients of different aggressiveness degree, were analyzed by sandwich ELLA (Enzyme Linked Lectin Assay) using PhoSL and SNA. Changes in the levels of specific glycosylation determinants, that in serum PSA samples were indicative of PCa aggressiveness, were not found in PSA from DRE urine samples. Although urine is a simpler matrix for analyzing PSA glycosylation compared to serum, an immunopurification step was necessary to specifically detect the glycans on the PSA molecule. Those specific glycosylation determinants on urinary PSA were however not useful to improve PCa diagnosis. This could be probably due to the low proportion of PSA from the tumor in urine samples, which precludes the identification of aberrantly glycosylated PSA. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Correlates and consequences of exposure to video game violence: hostile personality, empathy, and aggressive behavior.

    Science.gov (United States)

    Bartholow, Bruce D; Sestir, Marc A; Davis, Edward B

    2005-11-01

    Research has shown that exposure to violent video games causes increases in aggression, but the mechanisms of this effect have remained elusive. Also, potential differences in short-term and long-term exposure are not well understood. An initial correlational study shows that video game violence exposure (VVE) is positively correlated with self-reports of aggressive behavior and that this relation is robust to controlling for multiple aspects of personality. A lab experiment showed that individuals low in VVE behave more aggressively after playing a violent video game than after a nonviolent game but that those high in VVE display relatively high levels of aggression regardless of game content. Mediational analyses show that trait hostility, empathy, and hostile perceptions partially account for the VVE effect on aggression. These findings suggest that repeated exposure to video game violence increases aggressive behavior in part via changes in cognitive and personality factors associated with desensitization.

  8. Health Care Workers' Experiences of Aggression.

    Science.gov (United States)

    Kerr, Katelyn; Oram, Joanne; Tinson, Helen; Shum, David

    2017-10-01

    To identify the prevalence of patient aggression against health care workers, the consequences and coping mechanisms. Retrospective cross-sectional design. 50 participants comprised 37 nurses, 1 ward staff, 12 allied health staff employed in two brain injury wards with experience ranging from 3months to 34years. Neurosciences and Brain Injury Rehabilitation wards of a metropolitan tertiary hospital in Brisbane. Researcher designed self-report questionnaire. 98% of respondents had experienced aggression during their health care careers with an average of 143.93 events. Physical injuries had been sustained by 40% of staff, psychological injury by 82%, but only 12% sought treatment. Verbal aggression related to receiving a psychological injury (r=0.305, paggression made it more likely the person would also experience the other types of aggression. Verbal aggression was correlated with physical aggression (r=0.429, paggression (r=0.286, paggression was correlated with non-verbal aggression (r=0.333, paggression is prevalent and of serious concern for staff working in hospital settings. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Relationship Between Scarring and Dog Aggression in Pit Bull-Type Dogs Involved in Organized Dogfighting

    Directory of Open Access Journals (Sweden)

    Katherine A. Miller

    2016-11-01

    Full Text Available When pit bull-type dogs are seized in an investigation of organized dogfighting, heavily scarred dogs are often assumed to be highly dog aggressive due to a history of fighting. These dogs may be deemed dangerous and euthanized based on scarring alone. We analyzed our existing data on dogs seized from four dogfighting investigations, examining the relationship between the dogs’ scars with aggression towards other dogs. Scar and wound data were tallied in three body zones where dogfighting injuries tend to be concentrated. Dog aggression was assessed using a model dog and a friendly stimulus dog in a standardized behavior evaluation. Scarring and dog aggression were significantly related, more strongly among male (Fisher’s Exact p < 0.001 than female dogs (Fisher’s Exact p = 0.05. Ten or more scars in the three body zones was a reasonable threshold with which to classify a dog as high risk for dog aggression: 82% of males and 60% of females with such scarring displayed dog aggression. However, because many unscarred dogs were dog aggressive while some highly scarred dogs were not, we recommend collecting behavioral information to supplement scar counts when making disposition decisions about dogs seized in dogfighting investigations.

  10. Determination of the neutralization depth of concrete under the aggressive environment influence

    Science.gov (United States)

    Morzhukhina, Anastasia; Nikitin, Stanislav; Akimova, Elena

    2018-03-01

    Aggressive environments have a significant impact on destruction of many reinforced concrete structures, such as high-rise constructions or chemical plants. For example, some high-rise constructions are equipped with a swimming pool, so they are exposed to chloride ions in the air. Penetration of aggressive chemical substances into the body of concrete contributes to acceleration of reinforced concrete structure corrosion that in turn leads to load bearing capacity loss and destruction of the building. The article considers and analyzes the main technologies for calculating penetration depth of various aggressive substances into the body of concrete. The calculation of corrosion depth was made for 50-year service life.

  11. Verbal Aggressiveness Among Physicians and Trainees.

    Science.gov (United States)

    Lazarus, Jenny Lynn; Hosseini, Motahar; Kamangar, Farin; Levien, David H; Rowland, Pamela A; Kowdley, Gopal C; Cunningham, Steven C

    2016-01-01

    To better understand verbal aggressiveness among physicians and trainees, including specialty-specific differences. The Infante Verbal Aggressiveness Scale (IVAS) was administered as part of a survey to 48 medical students, 24 residents, and 257 attending physicians. The 72 trainees received the IVAS and demographic questions, whereas the attending physicians received additional questions regarding type of practice, career satisfaction, litigation, and personality type. The IVAS scores showed high reliability (Cronbach α = 0.83). Among all trainees, 56% were female with mean age 28 years, whereas among attending physicians, 63% were male with mean age 50 years. Average scores of trainees were higher than attending physicians with corresponding averages of 1.88 and 1.68, respectively. Among trainees, higher IVAS scores were significantly associated with male sex, non-US birthplace, choice of surgery, and a history of bullying. Among attending physicians, higher IVAS scores were significantly associated with male sex, younger age, self-reported low-quality of patient-physician relationships, and low enjoyment talking to patients. General surgery and general internal medicine physicians were significantly associated with higher IVAS scores than other specialties. General practitioners (surgeons and medical physicians) had higher IVAS scores than the specialists in their corresponding fields. No significant correlation was found between IVAS scores and threats of legal action against attending physicians, or most personality traits. Additional findings regarding bullying in medical school, physician-patient interactions, and having a method to deal with inappropriate behavior at work were observed. Individuals choosing general specialties display more aggressive verbal communication styles, general surgeons displaying the highest. The IVAS scoring system may identify subgroups of physicians with overly aggressive (problematic) communication skills and may provide a

  12. Gibbon Aggression During Introductions: An International Survey.

    Science.gov (United States)

    Harl, Heather; Stevens, Lisa; Margulis, Susan W; Petersen, Jay

    2016-01-01

    Little is known regarding the prevalence of aggression seen during introductions of captive gibbons (Hylobatidae). In this study, an online survey was developed to quantify and collect contextual details regarding the frequency and types of aggression seen during introductions of captive gibbons (Hylobatidae). Nineteen percent of institutions (17 institutions) reported observing aggression, and 6 of these institutions recorded multiple instances of aggression, though a vast majority of these cases resulted in mild injuries or none at all. The female was the primary aggressor in 23% of cases, the male was the primary aggressor in 58% of cases, and both were the primary aggressor in 1 case. Although these aggressive interactions were often not associated with a known cause, 27% of cases were associated with food displacement. In most cases, management changes, including trying new pairings, greatly reduced situational aggression, suggesting that individual personalities may play a factor in aggression. These data begin to explain the extent of aggression observed in captive gibbons; future studies will address possible correlations with aggression and introduction techniques.

  13. Cool and hot executive function as predictors of aggression in early childhood: Differentiating between the function and form of aggression.

    Science.gov (United States)

    Poland, Sarah E; Monks, Claire P; Tsermentseli, Stella

    2016-06-01

    Executive function (EF) has been implicated in childhood aggression. Understanding of the role of EF in aggression has been hindered, however, by the lack of research taking into account the function and form of aggression and the almost exclusive focus on cool EF. This study examined the role of cool and hot EF in teacher reported aggression, differentiating between reactive and proactive as well as physical and relational aggression. Children (N = 106) completed laboratory tasks measuring cool (inhibition, planning, working memory) and hot EF (affective decision-making, delay of gratification). Cool, but not hot, EF significantly contributed to understanding of childhood aggression. Inhibition was a central predictor of childhood aggression. Planning and working memory, in contrast, were significant independent predictors of proactive relational aggression only. Added to this, prosocial behaviour moderated the relationship between working memory and reactive relational aggression. This study therefore suggests that cool EF, particularly inhibition, is associated with childhood aggression across the different functions and forms. © 2015 The British Psychological Society.

  14. Competitive Aggression without Interaction: Effects of Competitive versus Cooperative Instructions on Aggressive Behavior in Video Games.

    Science.gov (United States)

    Anderson, Craig A.; Morrow, Melissa

    1995-01-01

    Extended and tested Deutsch's theory of competition effects. Predicted that people view competitive situations as inherently more aggressive than cooperative ones. Predicted that leading people to think of an aggressive situation in competitive terms would increase aggressive behavior. Increase of kill ratio occurred in absence of changes in…

  15. Carbonic anhydrase IX inhibition affects viability of cancer cells adapted to extracellular acidosis.

    Science.gov (United States)

    Andreucci, Elena; Peppicelli, Silvia; Carta, Fabrizio; Brisotto, Giulia; Biscontin, Eva; Ruzzolini, Jessica; Bianchini, Francesca; Biagioni, Alessio; Supuran, Claudiu T; Calorini, Lido

    2017-12-01

    Among the players of the adaptive response of cancer cells able to promote a resistant and aggressive phenotype, carbonic anhydrase IX (CAIX) recently has emerged as one of the most relevant drug targets. Indeed, CAIX targeting has received a lot of interest, and selective inhibitors are currently under clinical trials. Hypoxia has been identified as the master inductor of CAIX, but, to date, very few is known about the influence that another important characteristic of tumor microenvironment, i.e., extracellular acidosis, exerts on CAIX expression and activity. In the last decades, acidic microenvironment has been associated with aggressive tumor phenotype endowed with epithelial-to-mesenchymal transition (EMT) profile, high invasive and migratory ability, apoptosis, and drug resistance. We demonstrated that melanoma, breast, and colorectal cancer cells transiently and chronically exposed to acidified medium (pH 6.7 ± 0.1) showed a significantly increased CAIX expression compared to those grown in standard conditions (pH 7.4 ± 0.1). Moreover, we observed that the CAIX inhibitor FC16-670A (also named SLC-0111, which just successfully ended phase I clinical trials) not only prevents such increased expression under acidosis but also promotes apoptotic and necrotic programs only in acidified cancer cells. Thus, CAIX could represent a selective target of acidic cancer cells and FC16-670A inhibitor as a useful tool to affect this aggressive subpopulation characterized by conventional therapy escape. Cancer cells overexpress CAIX under transient and chronic extracellular acidosis. Acidosis-induced CAIX overexpression is NF-κB mediated and HIF-1α independent. FC16-670A prevents CAIX overexpression and induces acidified cancer cell death.

  16. The Aggression Observation Short Form Identified Episodes Not Reported on the Staff Observation Aggression Scale-Revised

    DEFF Research Database (Denmark)

    Hvidhjelm, Jacob; Sestoft, Dorte; Bjørner, Jakob Bue

    2014-01-01

    The purpose of this study is to evaluate the underreporting of violence and aggression on the Staff Observation Aggression Scale-Revised (SOAS-R) when compared to a simpler assessment: the Aggression Observation Short Form (AOS). During a period of one year, two open and two closed wards gathered...... for open wards and for patients with short admission lengths. Standard instruments such as the SOAS-R underreport aggressive episodes by 45% or more. Underreporting can be reduced by introducing shorter instruments, but it cannot be completely eliminated....

  17. Violence among peoples in the light of human frustration and aggression.

    Science.gov (United States)

    de Gaay Fortman, Bas

    2005-12-05

    This article sets out to provide a general background to the study of aggression in the social sciences, with a particular focus on its link to collective violence. While the study of what happens in the human brain appears to be already highly complex, analysis of violent behavior appears to be even more intricate. A deductive system in the sense of a general and clear system of propositions logically connected to one another is not feasible, principally because contrary to the natural sciences there are no verities but merely "stylized facts." One of these concerns the setting of human aggression in the light of frustration, as argued in the frustration-aggression hypothesis developed by Dollard et al. in 1939. Apart from conceiving of aggression as a pure human instinct, it may also be seen as externally driven, while a third possibility concerns culturally "learned" aggression. Proof of the latter is that the strongest correlation appears to be that between current violence and previous manifestations thereof. Attention is paid to the way in which Gurr has rooted his relative deprivation theory on causes of collective violence among peoples in mechanisms of frustration and aggression. That theory is taken a bit further in terms of "perceived acquirement failure," which appears to be highly connected to the role of the state. Based on certain observations by Hannah Arendt, the argument then proceeds to violence as a manifestation of powerlessness. Finally, this leads to a discussion of justice as a crucial factor in what Durkheim used to call a "right to conflict." In this way, human aggression is placed in a broad socio-economic context.

  18. Breast cancer staging with MR imaging

    International Nuclear Information System (INIS)

    Smathers, R.L.; D'Amelio, F.; Stockdale, F.

    1989-01-01

    Forty-three patients with biopsy-proved breast cancer underwent MR staging of the cervicothoracic spine, lumbosacral spine, liver, and thorax. In all cases, these findings have been compared with the results of clinical staging, laboratory tests, chest radiography, and radionuclide bone scanning. MR imaging was a valuable staging tool for patients with more than minimal breast cancer and indications for radionuclide bone scanning. MR imaging had the greatest clinical importance when it identified thoracic soft-tissue abnormalities, including axillary., lateral thoracic, supraclavicular, and mediastinal lymphadenopathy. The coronal and sagittal views were very valuable for detection of chest wall invasion, sternal involvement, and internal mammary adenopathy. Negative MR staging clinically reassured patients that aggressive local therapy bad curative potential. Positive MR staging avoided inappropriate aggressive local therapy and mastectomy. MR imaging can be recommended for improved breast cancer staging in patients with newly diagnosed breast cancer who have more than minimal disease

  19. Verbal and physical client aggression - A longitudinal analysis of professional caregivers' psychophysiological stress response and burnout.

    Science.gov (United States)

    Kind, Nina; Eckert, Anne; Steinlin, Célia; Fegert, Jörg M; Schmid, Marc

    2018-05-02

    We investigated the impact of verbal and physical client aggression on risk of developing high hair cortisol concentration (HCC) as an indicator of chronic stress exposure and burnout in a Swiss population of professional caregivers working in youth residential care. Participants (n = 121; 62.0% women) reported on client aggression and burnout symptoms and provided hair samples at four annual sampling points. HCC was determined in the first 1.5 cm hair segment. Sociodemographic variables, private stressors, burnout symptoms, and HCC were compared between participants reporting either 'no aggression', 'verbal' aggression, or 'verbal + physical' aggression. Cox proportional hazards regressions were calculated to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association between client aggression and risk of high HCC or burnout over the course of three years. Professional caregivers reporting 'verbal + physical' aggression had higher HCC, more cognitive burnout symptoms, and greater burden in interpersonal domains. Both 'verbal' and 'verbal + physical' aggression were positively associated with burnout risk (verbal: HR = 1.83; 95% CI = 1.27-2.65; verbal + physical: HR = 2.44, 95% CI = 1.56-3.84). 'Verbal + physical' aggression was positively associated with risk of high HCC (HR = 1.58; 95% CI = 1.07-2.36). This longitudinal analysis suggested that psychophysiological stress response is primarily associated with combined verbal and physical aggression. The emotional wearing-down associated with verbal aggression should however not be disregarded. Our exploratory findings could have implications for youth welfare policy, clinical child psychiatry, and future research. Copyright © 2018. Published by Elsevier Ltd.

  20. Behavioural strategies of aggressive and non-aggressive male mice in active shock avoidance

    NARCIS (Netherlands)

    Benus, R.F.; Bohus, B.; Koolhaas, J.M.; Oortmerssen, G.A. van

    1989-01-01

    The hypothesis, partly based on findings in social interactions, that aggressive mice generally adopt an active behavioural strategy (cf. fight-flight) in threatening situations, while non-aggressive ones generally assume a passive strategy (cf. conservation-withdrawal) was tested using a two-way

  1. Checkpoint Kinase 1 Expression Predicts Poor Prognosis in Nigerian Breast Cancer Patients.

    Science.gov (United States)

    Ebili, Henry Okuchukwu; Iyawe, Victoria O; Adeleke, Kikelomo Rachel; Salami, Babatunde Abayomi; Banjo, Adekunbiola Aina; Nolan, Chris; Rakha, Emad; Ellis, Ian; Green, Andrew; Agboola, Ayodeji Olayinka Johnson

    2018-02-01

    Checkpoint kinase 1 (CHEK1), a DNA damage sensor and cell death pathway stimulator, is regarded as an oncogene in tumours, where its activities are considered essential for tumourigenesis and the survival of cancer cells treated with chemotherapy and radiotherapy. In breast cancer, CHEK1 expression has been associated with an aggressive tumour phenotype, the triple-negative breast cancer subtype, an aberrant response to tamoxifen, and poor prognosis. However, the relevance of CHEK1 expression has, hitherto, not been investigated in an indigenous African population. We therefore aimed to investigate the clinicopathological, biological, and prognostic significance of CHEK1 expression in a cohort of Nigerian breast cancer cases. Tissue microarrays of 207 Nigerian breast cancer cases were tested for CHEK1 expression using immunohistochemistry. The clinicopathological, molecular, and prognostic characteristics of CHEK1-positive tumours were determined using the Chi-squared test and Kaplan-Meier and Cox regression analyses in SPSS Version 16. Nuclear expression of CHEK1 was present in 61% of breast tumours and was associated with tumour size, triple-negative cancer, basal-like phenotype, the epithelial-mesenchymal transition, p53 over-expression, DNA homologous repair pathway dysfunction, and poor prognosis. The rate expression of CHEK1 is high in Nigerian breast cancer cases and is associated with an aggressive phenotype and poor prognosis.

  2. Cognitive and emotional demands of black humour processing: the role of intelligence, aggressiveness and mood.

    Science.gov (United States)

    Willinger, Ulrike; Hergovich, Andreas; Schmoeger, Michaela; Deckert, Matthias; Stoettner, Susanne; Bunda, Iris; Witting, Andrea; Seidler, Melanie; Moser, Reinhilde; Kacena, Stefanie; Jaeckle, David; Loader, Benjamin; Mueller, Christian; Auff, Eduard

    2017-05-01

    Humour processing is a complex information-processing task that is dependent on cognitive and emotional aspects which presumably influence frame-shifting and conceptual blending, mental operations that underlie humour processing. The aim of the current study was to find distinctive groups of subjects with respect to black humour processing, intellectual capacities, mood disturbance and aggressiveness. A total of 156 adults rated black humour cartoons and conducted measurements of verbal and nonverbal intelligence, mood disturbance and aggressiveness. Cluster analysis yields three groups comprising following properties: (1) moderate black humour preference and moderate comprehension; average nonverbal and verbal intelligence; low mood disturbance and moderate aggressiveness; (2) low black humour preference and moderate comprehension; average nonverbal and verbal intelligence, high mood disturbance and high aggressiveness; and (3) high black humour preference and high comprehension; high nonverbal and verbal intelligence; no mood disturbance and low aggressiveness. Age and gender do not differ significantly, differences in education level can be found. Black humour preference and comprehension are positively associated with higher verbal and nonverbal intelligence as well as higher levels of education. Emotional instability and higher aggressiveness apparently lead to decreased levels of pleasure when dealing with black humour. These results support the hypothesis that humour processing involves cognitive as well as affective components and suggest that these variables influence the execution of frame-shifting and conceptual blending in the course of humour processing.

  3. Imaging primary prostate cancer with 11C-Choline PET/CT: relation to tumour stage, Gleason score and biomarkers of biologic aggressiveness

    International Nuclear Information System (INIS)

    Chen, Ji; Zhao, Yong; Li, Xin; Sun, Peng; Wang, Muwen; Wang, Ridong; Jin, Xunbo

    2012-01-01

    As a significant overlap of 11C-Choline standardized uptake value (SUV) between prostate cancer and benign prostate hyperplasia (BPH) tissue, controversy exists regarding the clinical value of 11C-Choline PET/CT scan in primary prostate cancer. In this study, the SUVmax of the prostate lesions and the pelvic muscles were measured and their ratios (SUVmax-P/M ratio) were calculated. Then we evaluated whether the tracer 11C-Choline uptake, quantified as SUVmax-P/M ratio, correlated with tumour stage, Gleason score, and expression levels of several biomarkers of aggressiveness. Twenty-six patients with primary prostate cancer underwent 11C-Choline PET/CT. Tumour specimens from these patients were graded histopathologically, and immunnohistochemistry for Ki-67, CD31, androgen receptor (AR), Her-2/neu, Bcl-2, and PTEN were performed. Both SUVmax and SUVmax-P/M ratio showed no significant difference between patients with tumour stage II and III, but significantly elevated in patients with tumour stage IV. SUVmax-P/M ratio was also significantly higher in lesions with Gleason score of 4+3 or higher versus less than or equal to 3+4. SUVmax-P/M ratio was found significantly correlated with expression levels of Ki-67 and CD31. In addition, a higher SUVmax-P/M ratio was demonstrated in Her-2/neu positive subgroup than negative subgroup. At the same time, Gleason score and expression levels of these biomarkers showed no significant association with SUVmax. Using the parameter SUVmax-P/M ratio, 11C-Choline PET/CT may be a valuable non-invasive imaging technology in the diagnosis of primary prostate cancer

  4. Longitudinal effects of violent video games on aggression in Japan and the United States.

    Science.gov (United States)

    Anderson, Craig A; Sakamoto, Akira; Gentile, Douglas A; Ihori, Nobuko; Shibuya, Akiko; Yukawa, Shintaro; Naito, Mayumi; Kobayashi, Kumiko

    2008-11-01

    Youth worldwide play violent video games many hours per week. Previous research suggests that such exposure can increase physical aggression. We tested whether high exposure to violent video games increases physical aggression over time in both high- (United States) and low- (Japan) violence cultures. We hypothesized that the amount of exposure to violent video games early in a school year would predict changes in physical aggressiveness assessed later in the school year, even after statistically controlling for gender and previous physical aggressiveness. In 3 independent samples, participants' video game habits and physically aggressive behavior tendencies were assessed at 2 points in time, separated by 3 to 6 months. One sample consisted of 181 Japanese junior high students ranging in age from 12 to 15 years. A second Japanese sample consisted of 1050 students ranging in age from 13 to 18 years. The third sample consisted of 364 United States 3rd-, 4th-, and 5th-graders ranging in age from 9 to 12 years. RESULTS. Habitual violent video game play early in the school year predicted later aggression, even after controlling for gender and previous aggressiveness in each sample. Those who played a lot of violent video games became relatively more physically aggressive. Multisample structure equation modeling revealed that this longitudinal effect was of a similar magnitude in the United States and Japan for similar-aged youth and was smaller (but still significant) in the sample that included older youth. These longitudinal results confirm earlier experimental and cross-sectional studies that had suggested that playing violent video games is a significant risk factor for later physically aggressive behavior and that this violent video game effect on youth generalizes across very different cultures. As a whole, the research strongly suggests reducing the exposure of youth to this risk factor.

  5. Psychiatric nurses' experiences with inpatient aggression

    NARCIS (Netherlands)

    Nijman, H.; Bowers, L.; Oud, N.; Jansen, G.

    2005-01-01

    Using a survey instrument, the experiences of psychiatric nurses with inpatient aggression were investigated in East London, U.K. On this "Perceptions of Prevalence Of Aggression Scale" (POPAS), annual experiences with 15 types of disruptive and aggressive behavior were rated anonymously. Staff

  6. Nutritional Interventions for Cancer-induced Cachexia

    OpenAIRE

    Gullett, Norleena P.; Mazurak, Vera; Hebbar, Gautam; Ziegler, Thomas R.

    2011-01-01

    Cancer-induced cachexia remains a significant cause of morbidity and mortality in cancer treatment. Cancer research and development continues at an aggressive pace and yet a degree of cancer-induced cachexia is experienced by up to 80% of advanced stage cancer patients. Unfortunately, there are no established treatment regimens for this condition. Weight loss and fatigue consistently appear in patient oncologic histories and progress notes. However, few oncologists fully understand the pathol...

  7. Relationship Between Scarring and Dog Aggression in Pit Bull-Type Dogs Involved in Organized Dogfighting

    Science.gov (United States)

    Miller, Katherine A.; Touroo, Rachel; Spain, C. Victor; Jones, Kelly; Reid, Pamela; Lockwood, Randall

    2016-01-01

    Simple Summary Organizations responsible for placing dogs seized from dogfighting investigations often must determine if a particular dog should be euthanized because it is too dangerous or if it is safe to place the dog in an adoptive home. In this study, we examine whether the extent of scarring from dog fighting is a reliable predictor of aggression towards other dogs and therefore could be used to help make that decision. We found that dogs with 10 or more scars in the three body zones where dogfighting injuries tend to be concentrated were more likely, on average, to show aggression to other dogs. The relationship is imperfect, however. Many unscarred dogs were dog aggressive while some highly scarred dogs were not. Therefore, we recommend also assessing a dog’s behavior before making decisions about its disposition. Abstract When pit bull-type dogs are seized in an investigation of organized dogfighting, heavily scarred dogs are often assumed to be highly dog aggressive due to a history of fighting. These dogs may be deemed dangerous and euthanized based on scarring alone. We analyzed our existing data on dogs seized from four dogfighting investigations, examining the relationship between the dogs’ scars with aggression towards other dogs. Scar and wound data were tallied in three body zones where dogfighting injuries tend to be concentrated. Dog aggression was assessed using a model dog and a friendly stimulus dog in a standardized behavior evaluation. Scarring and dog aggression were significantly related, more strongly among male (Fisher’s Exact p < 0.001) than female dogs (Fisher’s Exact p = 0.05). Ten or more scars in the three body zones was a reasonable threshold with which to classify a dog as high risk for dog aggression: 82% of males and 60% of females with such scarring displayed dog aggression. However, because many unscarred dogs were dog aggressive while some highly scarred dogs were not, we recommend collecting behavioral information to

  8. Patterns of Change in Adolescent Dating Victimization and Aggression During Middle School.

    Science.gov (United States)

    Goncy, Elizabeth A; Farrell, Albert D; Sullivan, Terri N

    2018-03-01

    Although mounting evidence suggests dating victimization and aggression begin in early adolescence, little work has examined the pattern of these behaviors across this age. This longitudinal study examined trajectories of dating victimization and aggression across middle school using 12 waves of data. A sample of early adolescents (N = 1369, 52.3% girls; 83% African American; 15% Hispanic or Latino) residing in an urban, economically disadvantaged area participated in this study. Youth completed measures of dating victimization and aggression quarterly across the 3 years of middle school. Although results indicated a general trend of increasing dating victimization and aggression across middle school, variation existed for boys and girls. Specifically, girls showed increasing patterns of both, whereas boys remained relatively stable across time. Dating victimization and aggression were also highly correlated across time. These findings support the implementation and refinement of prevention programming aimed at preventing and reducing dating aggression and victimization in middle school.

  9. [Lorenz was right, or does aggressive energy accumulate?].

    Science.gov (United States)

    Kudriavtseva, N N

    2004-06-01

    Evidence supporting the fact that inherited mechanisms of regulation of aggressive behavior as a result of a repeated experience of aggression ending in victories are transformed into pathological mechanisms based on accumulation of neurochemical shifts in the brain, enhancing aggressiveness, and forming aggressive motivation in aggressive winners. This confirms the concept by Lorenz on the existence of a mechanism (but not instinct) of a spontaneous accumulation of aggressive energy that needs a discharge and formation of permanent attraction to manifestation of aggression.

  10. Effect of Mindfulness-Based Cognitive Therapy (MBCT on reducing aggression in students

    Directory of Open Access Journals (Sweden)

    Salar Faramarzi

    2014-11-01

    Full Text Available Background: Students’ aggression at schoolshas attracted the attention of many professionals and researchers. The purpose of this study was to analyze the effect of mindfulness-based cognitive therapy on the reduction of male secondary students' aggression in Kermanshah. Methods: In this experimental study, a pretest-posttest control group design was used. A total of 400 students were randomly selected from among the high school male students in Kermanshah using multistage sampling. Of these, 40 students who had a higher mean score were randomly divided into control and experimental groups. The experimental group underwent with mindfulness-based cognitive therapy once a week for eight sessions. The subjects completed Buss and Perry Aggression Questionnaire (1992 twice, one before treatment and another after treatment. The data were analyzed by multivariate analysis of covariance (MANCOVA. Results: The results of multivariate analysis of covariance showed that after removing the effect of pretest, the experimental group indicated a significant reduction compared to the control group in the total aggression scale (F=1059.531; P<0.001. Also, after removing the effect of the pretest, the experimental group experienced a significant decrease compared to the control group at the micro scales of aggressive feeling (F=639.936; P<0.001, the subscales of aggressive thoughts (F=154.240; P<0.001, and aggressive behaviors (F=502.836; P<0.001,. Conclusion: This study showed that mindfulness-based cognitive therapy reduced aggression in all three components of aggressive behavior, aggressive thoughts and aggressive feelings in the students.

  11. Aggression at Work

    DEFF Research Database (Denmark)

    Høgh, Annie

    Very few international and no Danish studies investigating the consequences of exposure to both physical and psychological aggression at work have been published. The aim of the present thesis is therefore to investigate the prevalence and consequences of different forms of physical...... and psychological aggression. Four papers are included in the thesis and they address the prevalence and long-term consequences of physical and psychological aggression in the form of nasty teasing and violence and/or threats of violence and short-term consequences of bullying at work including physiological stress...... response in victims. It was also an aim of the thesis to study whether aspects of the work environment, social climate and personal dispositions would mediate potential relationships between exposure to bullying, nasty teasing or violence and different health effects and stress reactions.      The study...

  12. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer

    NARCIS (Netherlands)

    Peifer, Martin; Fernandez-Cuesta, Lynnette; Sos, Martin L.; George, Julie; Seidel, Danila; Kasper, Lawryn H.; Plenker, Dennis; Leenders, Frauke; Sun, Ruping; Zander, Thomas; Menon, Roopika; Koker, Mirjam; Dahmen, Ilona; Mueller, Christian; Di Cerbo, Vincenzo; Schildhaus, Hans-Ulrich; Altmueller, Janine; Baessmann, Ingelore; Becker, Christian; de Wilde, Bram; Vandesompele, Jo; Boehm, Diana; Ansen, Sascha; Gabler, Franziska; Wilkening, Ines; Heynck, Stefanie; Heuckmann, Johannes M.; Lu, Xin; Carter, Scott L.; Cibulskis, Kristian; Banerji, Shantanu; Getz, Gad; Park, Kwon-Sik; Rauh, Daniel; Gruetter, Christian; Fischer, Matthias; Pasqualucci, Laura; Wright, Gavin; Wainer, Zoe; Russell, Prudence; Petersen, Iver; Chen, Yuan; Stoelben, Erich; Ludwig, Corinna; Schnabel, Philipp; Hoffmann, Hans; Muley, Thomas; Brockmann, Michael; Engel-Riedel, Walburga; Muscarella, Lucia A.; Fazio, Vito M.; Groen, Harry; Timens, Wim; Sietsma, Hannie; Thunnissen, Erik; Smit, Egbert; Heideman, Danielle A. M.; Snijders, Peter J. F.; Cappuzzo, Federico; Ligorio, Claudia; Damiani, Stefania; Field, John; Solberg, Steinar; Brustugun, Odd Terje; Lund-Iversen, Marius; Saenger, Joerg; Clement, Joachim H.; Soltermann, Alex; Moch, Holger; Weder, Walter; Solomon, Benjamin; Soria, Jean-Charles; Validire, Pierre; Besse, Benjamin; Brambilla, Elisabeth; Brambilla, Christian; Lantuejoul, Sylvie; Lorimier, Philippe; Schneider, Peter M.; Hallek, Michael; Pao, William; Meyerson, Matthew; Sage, Julien; Shendure, Jay; Schneider, Robert; Buettner, Reinhard; Wolf, Juergen; Nuernberg, Peter; Perner, Sven; Heukamp, Lukas C.; Brindle, Paul K.; Haas, Stefan; Thomas, Roman K.

    2012-01-01

    Small-cell lung cancer (SCLC) is an aggressive lung tumor subtype with poor prognosis(1-3). We sequenced 29 SCLC exomes, 2 genomes and 15 transcriptomes and found an extremely high mutation rate of 7.4 +/- 1 protein-changing mutations per million base pairs. Therefore, we conducted integrated

  13. Inhibition of heregulin expression blocks tumorigenicity and metastasis of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, Miaw-Sheue; Shamon-Taylor, Lisa A.; Mehmi, Inderjit; Tang, Careen K.; Cardillo, Marina; Lupu, Ruth

    2001-12-20

    The growth factor Heregulin (HRG) is expressed in 30% of breast cancer tumors. HRG induces tumorigenicity and metastasis of breast cancer cells. Our investigation into whether blockage of HRG reduces the aggressiveness of breast cancer cells demonstrated that transfection of MDA-MB-231 with an HRG antisense cDNA suppressed proliferation, tumorigenicity, and metastasis. Blockage of the aggressive phenotype is mediated possibly through inactivation of the erbB signaling pathways and a decrease in MMP-9 activity. Our study is the first to report that HRG is a key promoter of breast cancer progression and should be deemed as a potential target in developing therapies for the treatment of breast carcinomas.

  14. The socializing effect of classroom aggression on the development of aggression and social rejection: A two-wave multilevel analysis.

    Science.gov (United States)

    Rohlf, Helena; Krahé, Barbara; Busching, Robert

    2016-10-01

    The current study examined the moderating effect of classroom aggression on the development of individual aggression and on the path from individual aggression to social rejection over time. The study included 1,284 elementary school children and consisted of two data waves 10months apart. At both time points, teachers assessed the children's physical and relational aggression and their social rejection status. Multi-level analyses revealed that the classroom level of relational aggression moderated the link between individual relational aggression at T1 and T2 (b=-0.18, 95% CI [-0.32, -0.05], psocial rejection (b=-0.12, 95% CI [-0.23, -0.003], psocial rejection in classrooms with a low level of relational aggression. Children were mainly influenced by their same-gender peers. Boys as a group had a greater influence than girls on their peers of either gender in the domain of relational aggression, whereas girls as a group had a greater influence in the domain of physical aggression. The contributions of analyzing cross-level interaction to understanding the developmental patterns of aggression and social rejection in middle childhood are discussed. Copyright © 2016 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

  15. Anti-aggressive effects of neuropeptide S independent of anxiolysis in male rats

    Directory of Open Access Journals (Sweden)

    Daniela I Beiderbeck

    2014-05-01

    Full Text Available Neuropeptide S (NPS exerts robust anxiolytic and memory enhancing effects, but only in a non-social context. In order to study whether NPS affects aggressive behavior we used Wistar rats bred for low (LAB and high (HAB levels of innate anxiety-related behaviour, respectively, which were both described to display increased levels of aggression compared with Wistar rats not selectively bred for anxiety (NAB. Male LAB, HAB and NAB rats were tested for aggressive behavior towards a male intruder rat within their home cage (10 min, resident-intruder [RI] test. Intracerebroventricular (icv infusion of NPS (1 nmol significantly reduced inter-male aggression in LAB rats, and tended to reduce aggression in HAB and NAB males. However, local infusion of NPS (0.2 or 0.1 nmol NPS into either the nucleus accumbens or the lateral hypothalamus did not influence aggressive behavior. Social investigation in the RI test and general social motivation assessed in the social preference paradigm were not altered by icv NPS. The anti-aggressive effect of NPS is most likely not causally linked to its anxiolytic properties, as intraperitoneal administration of the anxiogenic drug pentylenetetrazole decreased aggression in LAB rats whereas the anxiolytic drug diazepam did not affect aggression of HAB rats. Thus, although NPS has so far only been shown to exert effects on non-social behaviors, our results are the first demonstration of anti-aggressive effects of NPS in male rats.

  16. Medea: Aggression im Dienste weiblicher Subjektivierung Medea: How aggression works for female subjugation

    Directory of Open Access Journals (Sweden)

    Monika Gsell

    2003-11-01

    Full Text Available Aggression wurde in der Geschlechterforschung bisher meist nicht nur unter negativen Vorzeichen – nämlich als zerstörerische und fehlgeleitete Kraft – thematisiert und mit Gewalt in eins gesetzt, sondern darüberhinaus fast ausschließlich mit Männlichkeit konnotiert. Nur langsam setzt sich demgegenüber die Einsicht durch, dass Aggression zunächst einmal eine grundsätzlich positive Kraft ist, derer es zur Subjektivierung und Erlangung von Selbstbestimmung bedarf. Damit scheint nun auch eine fruchtbare Auseinandersetzung mit Weiblichkeit und Aggression möglich geworden zu sein. Ein lehrreicher Beitrag dazu ist Roxana Hidalgos Medea-Studie, gerade weil sie die eigentlich heiklen Fragen weder stellt noch beantwortet.So far, gender studies have tended to thematise aggression not only as a destructive, misdirected force, but one that is regarded almost without exception as masculine. Slowly, though, understanding is growing that aggresion should be viewed in principle as a positive force that is vital for the process of gaining subjectivity and self-determination. This insight seems to have opened the potential to discuss femininity and aggression in new and fruitful ways. Roxana Hidalgos’s study of Medea is an instructive contribution to this discussion – especially/above all because the author neither asks nor answers the really tricky questions.

  17. How Food Controls Aggression in Drosophila

    Science.gov (United States)

    Lim, Rod S.; Eyjólfsdóttir, Eyrún; Shin, Euncheol; Perona, Pietro; Anderson, David J.

    2014-01-01

    How animals use sensory information to weigh the risks vs. benefits of behavioral decisions remains poorly understood. Inter-male aggression is triggered when animals perceive both the presence of an appetitive resource, such as food or females, and of competing conspecific males. How such signals are detected and integrated to control the decision to fight is not clear. For instance, it is unclear whether food increases aggression directly, or as a secondary consequence of increased social interactions caused by attraction to food. Here we use the vinegar fly, Drosophila melanogaster, to investigate the manner by which food influences aggression. We show that food promotes aggression in flies, and that it does so independently of any effect on frequency of contact between males, increase in locomotor activity or general enhancement of social interactions. Importantly, the level of aggression depends on the absolute amount of food, rather than on its surface area or concentration. When food resources exceed a certain level, aggression is diminished, suggestive of reduced competition. Finally, we show that detection of sugar via Gr5a+ gustatory receptor neurons (GRNs) is necessary for food-promoted aggression. These data demonstrate that food exerts a specific effect to promote aggression in male flies, and that this effect is mediated, at least in part, by sweet-sensing GRNs. PMID:25162609

  18. Simultaneous use of alcohol with methamphetamine but not ecstasy linked with aggression among young adult stimulant users.

    Science.gov (United States)

    Leslie, Ellen M; Smirnov, Andrew; Cherney, Adrian; Wells, Helene; Legosz, Margot; Kemp, Robert; Najman, Jake M

    2017-07-01

    Illicit stimulants are often combined with alcohol in nightlife entertainment districts, an environment where aggressive behaviour commonly occurs. While alcohol and methamphetamine use are each associated with aggressive behaviour, relatively little is known about the impact of the combined use of alcohol and amphetamine-type stimulants (i.e., ecstasy [MDMA] and methamphetamine) on aggression. Analysis of longitudinal data from a population-based sample of Australian young adult amphetamine-type stimulant users (n=248) to examine: (a) prevalence and timing of simultaneous alcohol and amphetamine-type stimulant use and (b) predictors of ecstasy- and methamphetamine-related aggression and hostility. Prediction models of ecstasy- and methamphetamine-related aggression and hostility were developed using multivariate logistic regression. Simultaneous alcohol consumption and amphetamine-type stimulant use was prevalent, with drinking generally occurring before consuming amphetamine-type stimulants and while 'high'. Methamphetamine-related aggression and hostility was significantly associated with recurrent risky simultaneous methamphetamine and alcohol use (Adjusted Odds Ratio [AOR] 2.74, 95% CI 1.09-6.89), a high frequency and increasing use methamphetamine trajectory (AOR 7.23, 95% CI 1.27-41.03), and high trait aggression (AOR 5.78, 95% CI 2.53-13.20). In contrast, only trait aggression (moderate: AOR 3.01, 95% CI 1.55-5.84; high: AOR 5.02, 95% CI 2.38-10.61) was associated with ecstasy-related aggression and hostility. These findings indicate a link between risky patterns of simultaneous alcohol and methamphetamine use and methamphetamine-related aggression and hostility, independent of separate use of alcohol, methamphetamine and cannabis, trait aggression, psychosis, and gender. The policy challenges of amphetamine-type stimulant and alcohol use require a targeted, multidisciplinary approach. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Improvement of Prostate Cancer Diagnosis by Detecting PSA Glycosylation-Specific Changes.

    Science.gov (United States)

    Llop, Esther; Ferrer-Batallé, Montserrat; Barrabés, Sílvia; Guerrero, Pedro Enrique; Ramírez, Manel; Saldova, Radka; Rudd, Pauline M; Aleixandre, Rosa N; Comet, Josep; de Llorens, Rafael; Peracaula, Rosa

    2016-01-01

    New markers based on PSA isoforms have recently been developed to improve prostate cancer (PCa) diagnosis. However, novel approaches are still required to differentiate aggressive from non-aggressive PCa to improve decision making for patients. PSA glycoforms have been shown to be differentially expressed in PCa. In particular, changes in the extent of core fucosylation and sialylation of PSA N-glycans in PCa patients compared to healthy controls or BPH patients have been reported. The objective of this study was to determine these specific glycan structures in serum PSA to analyze their potential value as markers for discriminating between BPH and PCa of different aggressiveness. In the present work, we have established two methodologies to analyze the core fucosylation and the sialic acid linkage of PSA N-glycans in serum samples from BPH (29) and PCa (44) patients with different degrees of aggressiveness. We detected a significant decrease in the core fucose and an increase in the α2,3-sialic acid percentage of PSA in high-risk PCa that differentiated BPH and low-risk PCa from high-risk PCa patients. In particular, a cut-off value of 0.86 of the PSA core fucose ratio, could distinguish high-risk PCa patients from BPH with 90% sensitivity and 95% specificity, with an AUC of 0.94. In the case of the α2,3-sialic acid percentage of PSA, the cut-off value of 30% discriminated between high-risk PCa and the group of BPH, low-, and intermediate-risk PCa with a sensitivity and specificity of 85.7% and 95.5%, respectively, with an AUC of 0.97. The latter marker exhibited high performance in differentiating between aggressive and non-aggressive PCa and has the potential for translational application in the clinic.

  20. Maladaptive dependency schemas, posttraumatic stress hyperarousal symptoms, and intimate partner aggression perpetration.

    Science.gov (United States)

    Kachadourian, Lorig K; Taft, Casey T; Holowka, Darren W; Woodward, Halley; Marx, Brian P; Burns, Anthony

    2013-10-01

    This study examined the associations between maladaptive dependency-related schemas, posttraumatic stress disorder (PTSD) hyperarousal symptoms, and intimate-partner psychological and physical aggression in a sample of court-referred men (N = 174) participating in a domestic-abuser-intervention program. The men were largely African American; average age was 33.5 years. The extent to which hyperarousal symptoms moderated the association between dependency schemas and aggression was also examined. Maladaptive dependency-related schemas were positively associated with severe psychological, and mild and severe physical aggression perpetration. Hyperarousal symptoms were positively associated with mild and severe psychological aggression, and mild physical aggression perpetration. Multiple regression analyses showed a significant interaction for mild physical aggression: For those with high levels of hyperarousal symptoms, greater endorsement of maladaptive dependency schemas was associated with the perpetration of aggression (B = 0.98, p = .001). For those with low levels of hyperarousal symptoms, there was no association between dependency schemas and aggression (B = 0.04, ns). These findings suggest that focusing on problematic dependency and PTSD-hyperarousal symptoms in domestic-abuser-intervention programs may be helpful, and that examining related variables as possible moderators between dependency schemas and intimate aggression would be a fruitful area for future research. Published 2013. This article is a US Government work and is in the public domain in the USA.