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Sample records for aggressive tumor characteristics

  1. Copy Number Alterations in Prostate Tumors and Disease Aggressiveness

    PubMed Central

    Cheng, Iona; Levin, Albert M.; Tai, Yu Chuan; Plummer, Sarah; Chen, Gary K.; Neslund-Dudas, Christine; Casey, Graham; Rybicki, Benjamin A.; Witte, John S.

    2011-01-01

    Detecting genomic alterations that result in more aggressive prostate cancer may improve clinical treatment and our understanding of the biology underlying this common but complex disease. To this end, we undertook a genome-wide copy number alterations (CNAs) study of clinicopathological characteristics of 62 prostate tumors using the Illumina 1M SNP array. The highest overall frequencies of CNAs were on chromosomes 8q (gains), 8p (loss and copy-neutral) and 6q (copy-loss). Combined loss and copy-neutral events were associated with increasing disease grade (p=0.03), stage (p=0.01), and diagnostic PSA (p=0.01). Further evaluation of CNAs using gene ontology identified pathways involved with disease aggressiveness. The ‘regulation of apoptosis’ pathway was associated with stage of disease (p=0.004), while the ‘reproductive cellular process’ pathway was associated with diagnostic PSA (p=0.00038). Specific genes within these pathways exhibited strong associations with clinical characteristics; for example, in the apoptosis pathway BNIP3L was associated with increasing prostate tumor stage (p=0.007). These findings confirm known regions of CNAs in prostate cancer, and localize additional regions and possible genes (e.g., BNIP3L, WWOX, and GATM) that may help clarify the genetic basis of prostate cancer aggressiveness. PMID:21965145

  2. Management of large aggressive nonfunctional pituitary tumors: experimental medical options when surgery and radiation fail.

    PubMed

    Miller, Brandon A; Rutledge, W Caleb; Ioachimescu, Adriana G; Oyesiku, Nelson M

    2012-10-01

    Pituitary adenomas are generally considered benign tumors; however, a subset of these tumors displays aggressive behavior and are not easily cured. The protocol for nonsurgical treatment of aggressive pituitary lesions is less standardized than that of other central nervous system tumors. Aggressive surgical treatment, radiation, dopamine agonists, antiangiogenic drugs, and other chemotherapeutics all have roles in the treatment of aggressive pituitary tumors. More studies are needed to improve outcomes for patients with aggressive pituitary tumors.

  3. Adaptive (TINT) Changes in the Tumor Bearing Organ Are Related to Prostate Tumor Size and Aggressiveness

    PubMed Central

    Adamo, Hanibal Hani; Strömvall, Kerstin; Nilsson, Maria; Halin Bergström, Sofia; Bergh, Anders

    2015-01-01

    In order to grow, tumors need to induce supportive alterations in the tumor-bearing organ, by us named tumor instructed normal tissue (TINT) changes. We now examined if the nature and magnitude of these responses were related to tumor size and aggressiveness. Three different Dunning rat prostate tumor cells were implanted into the prostate of immune-competent rats; 1) fast growing and metastatic MatLyLu tumor cells 2) fast growing and poorly metastatic AT-1 tumor cells, and 3) slow growing and non-metastatic G tumor cells. All tumor types induced increases in macrophage, mast cell and vascular densities and in vascular cell-proliferation in the tumor-bearing prostate lobe compared to controls. These increases occurred in parallel with tumor growth. The most pronounced and rapid responses were seen in the prostate tissue surrounding MatLyLu tumors. They were, also when small, particularly effective in attracting macrophages and stimulating growth of not only micro-vessels but also small arteries and veins compared to the less aggressive AT-1 and G tumors. The nature and magnitude of tumor-induced changes in the tumor-bearing organ are related to tumor size but also to tumor aggressiveness. These findings, supported by previous observation in patient samples, suggest that one additional way to evaluate prostate tumor aggressiveness could be to monitor its effect on adjacent tissues. PMID:26536349

  4. Inpatient verbal aggression: content, targets and patient characteristics.

    PubMed

    Stewart, D; Bowers, L

    2013-04-01

    Verbally aggressive behaviour on psychiatric wards is more common than physical violence and can have distressing consequences for the staff and patients who are subjected to it. Previous research has tended to examine incidents of verbal aggression in little detail, instead combining different types of aggressive behaviour into a single measure. This study recruited 522 adult psychiatric inpatients from 84 acute wards. Data were collected from nursing and medical records for the first 2 weeks of admission. Incidents of verbal aggression were categorized and associations with patient characteristics examined. There were 1398 incidents of verbal aggression in total, reported for half the sample. Types of verbal aggression were, in order of prevalence: abusive language, shouting, threats, expressions of anger and racist comments. There were also a large number of entries in the notes which did not specify the form of verbal aggression. Staff members were the most frequent target of aggression. A history of violence and previous drug use were consistently associated with verbal aggression. However, there were also some notable differences in patient variables associated with specific types of verbal aggression. Future studies should consider using multidimensional measures of verbal aggression.

  5. MMSET is overexpressed in cancers: Link with tumor aggressiveness

    SciTech Connect

    Kassambara, Alboukadel; Klein, Bernard Moreaux, Jerome

    2009-02-20

    MMSET is expressed ubiquitously in early development and its deletion is associated with the malformation syndrome called Wolf-Hirschhorn syndrome. It is involved in the t(4; 14) (p16; q32) chromosomal translocation, which is the second most common translocation in multiple myeloma (MM) and is associated with the worst prognosis. MMSET expression has been shown to promote cellular adhesion, clonogenic growth and tumorigenicity in multiple myeloma. MMSET expression has been recently shown to increase with ascending tumor proliferation activity in glioblastoma multiforme. These data demonstrate that MMSET could be implicated in tumor emergence and/or progression. Therefore, we compared the expression of MMSET in 40 human tumor types - brain, epithelial, lymphoid - to that of their normal tissue counterparts using publicly available gene expression data, including the Oncomine Cancer Microarray database. We found significant overexpression of MMSET in 15 cancers compared to their normal counterparts. Furthermore MMSET is associated with tumor aggressiveness or prognosis in many types of these aforementioned cancers. Taken together, these data suggest that MMSET potentially acts as a pathogenic agent in many cancers. The identification of the targets of MMSET and their role in cell growth and survival will be key to understand how MMSET is associated with tumor development.

  6. Deregulation of miR-183 and KIAA0101 in Aggressive and Malignant Pituitary Tumors

    PubMed Central

    Roche, Magali; Wierinckx, Anne; Croze, Séverine; Rey, Catherine; Legras-Lachuer, Catherine; Morel, Anne-Pierre; Fusco, Alfredo; Raverot, Gérald; Trouillas, Jacqueline; Lachuer, Joel

    2015-01-01

    Changes in microRNAs (miRNAs) expression in many types of cancer suggest that they may be involved in crucial steps during tumor progression. Indeed, miRNAs deregulation has been described in pituitary tumorigenesis, but few studies have described their role in pituitary tumor progression toward aggressiveness and malignancy. To assess the role of miRNAs within the hierarchical cascade of events in prolactin (PRL) tumors during progression, we used an integrative genomic approach to associate clinical–pathological features, global miRNA expression, and transcriptomic profiles of the same human tumors. We describe the specific down-regulation of one principal miRNA, miR-183, in the 8 aggressive (A, grade 2b) compared to the 18 non-aggressive (NA, grades 1a, 2a) PRL tumors. We demonstrate that it acts as an anti-proliferative gene by directly targeting KIAA0101, which is involved in cell cycle activation and inhibition of p53–p21-mediated cell cycle arrest. Moreover, we show that miR-183 and KIAA0101 expression significantly correlate with the main markers of pituitary tumors aggressiveness, Ki-67 and p53. These results confirm the activation of proliferation in aggressive and malignant PRL tumors compared to non-aggressive ones. Importantly, these data also demonstrate the ability of such an integrative genomic strategy, applied in the same human tumors, to identify the molecular mechanisms responsible for tumoral progression even from a small cohort of patients. PMID:26322309

  7. Radiation therapy in the treatment of aggressive fibromatoses (desmoid tumors).

    PubMed

    Kiel, K D; Suit, H D

    1984-11-15

    Twenty-five patients with aggressive fibromatoses (desmoid tumors) have been treated or followed in the Department of Radiation Medicine at the Massachusetts General Hospital between 1972 and 1982. Seventeen patients were treated by radiation, 4 for primary and 13 for recurrent disease. Seven patients were treated in conjunction with surgery. Partial or complete regression was achieved in 76%, and 59% are without evidence of disease (NED) at 9 to 94 months follow-up. Eight of ten patients treated primarily with radiation have achieved complete response without an attempt at resection (five) or have achieved stabilization (three) of their disease after some regression. Consistent complete control was seen with doses above 60 Gy. Periods to 27 months were required to observe complete responses. Only three failures within the radiation field were observed, two after low doses (22 and 24 Gy, respectively). Eight patients were seen after resection but with uncertain or histologically minimum positive margins, and were followed regularly and not treated. One patient has failed to date and is NED after resection. Radiation therapy is recommended in those situations where wide-field resection without significant morbidity is not possible for gross local disease. If minimally positive margins exist after resection in a patient who may be followed carefully, frequent follow-up and prompt treatment at recurrence may be an effective alternative to immediate radiation therapy.

  8. Parotid gland solitary fibrous tumor with mandibular bone destruction and aggressive behavior

    PubMed Central

    González-Otero, Teresa; Castro-Calvo, Alejandro; Ruiz-Bravo, Elena; Burgueño, Miguel

    2014-01-01

    Introduction: Solitary fibrous tumor is associated with serosal surfaces. Location in the salivary glands is extremely unusual. Extrathoracic tumors have an excellent prognosis associated with their benign clinical behavior. We report an aggressive and recurrent case of this tumor. We review the clinical presentation, inmunohistochemical profiles and therapeutic approaches. Case Report: A 73-years-old woman presented a mass in her right parotid gland. She had a past history of right superficial parotidectomy due to a neurilemoma. FNAB and magnetic resonance were non-specific. After a tumor resection, microscopic findings were spindled tumor cells with reactivity to CD34, bcl-2 and CD99 and the tumor was diagnosed as Solitary Fibrous Tumor. The patient suffered two recurrences and the tumor had a histological aggressive behavior and a destruction of the cortical bone of the mandible adjacent to the mass. A marginal mandibulectomy with an alveolar inferior nerve lateralization was performed. Conclusions: Solitary fibrous tumor is a very rare tumor. Usually, they are benign, but occasionally they can be aggressive. Complete resection is the most important prognostic factor and no evidence supports the efficacy of any therapy different to surgery. Due to the unknown prognosis and to the small number of cases reported, a long-term follow-up is guaranteed. Key words:Solitary fibrous tumor, parotid mass, parotid gland, salivary gland, rare tumors. PMID:25136435

  9. Aggression on inpatient units: Clinical characteristics and consequences.

    PubMed

    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.

  10. Aggression on inpatient units: Clinical characteristics and consequences.

    PubMed

    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. PMID:26892149

  11. Fibroblasts Regulate Variable Aggressiveness of Syndromic Keratocystic and Non-syndromic Odontogenic Tumors

    PubMed Central

    Hong, Y.-Y.; Yu, F.-Y.; Qu, J.-F.; Chen, F.; Li, T.-J.

    2014-01-01

    Keratocystic odontogenic tumors (KCOTs) are jaw lesions that can be either sporadic or associated with nevoid basal cell carcinoma syndrome, which typically occurs as multiple, aggressive lesions that can lead to large areas of bone destruction and resorption and cause major impairment and even jaw fracture. To clarify the role of fibroblasts in the aggressivness of syndromic (S-) as compared with non-syndromic (NS-) KCOTs, we assessed fibroblasts derived from 16 S- and NS-KCOTs for differences in cell proliferation, multilineage differentiation potential, alkaline phosphatase activity, and osteoclastogenic potential. S-KCOT fibroblasts had proliferative and osteoclastogenic capacity higher than those from NS-KCOTs, as evidenced by higher numbers of tartrate-resistant acid-phosphatase-positive multinuclear cells, expression of cyclooxygenase 2, and ratio of receptor activator of nuclear factor–kappa B ligand to osteoprotegerin. The osteogenic potential was higher for S- than for NS-KCOT fibroblasts and was associated with lower mRNA expression of runt-related transcription factor 2, collagen type I α1, osteocalcin, and osteopontin as well as reduced alkaline phosphatase activity. These results suggest that the distinct characteristics of fibroblasts in KCOTs are responsible for the greater aggressiveness observed in the syndromic subtype. Abbreviations: AP, alkaline phosphatase; CK, cytokeratin; COL1A1, collagen type I α1; COX-2, cyclooxygenase-2; GM-CSF, granulocyte-macrophage colony-stimulating factor; IL-1α, interleukin 1α; KCOT, keratocystic odontogenic tumor; NBCCS, nevoid basal cell carcinoma syndrome; NS-KCOT, non-syndrome-associated KCOT; OCN, osteocalcin; OPG, osteoprotegerin; OPN, osteopontin; RANKL, receptor activator of nuclear factor-kappa B ligand; Runx2, runt-related transcription factor 2; S-KCOT, syndrome-associated KCOT; TAF, tumor-associated fibroblast; and TRAP, tartrate-resistant acid phosphatase. PMID:24972872

  12. Temozolomide (Temodar®) and capecitabine (Xeloda®) treatment of an aggressive corticotroph pituitary tumor

    PubMed Central

    Thearle, Marie S.; Bruce, Jeffrey N.; Isaacson, Steven R.; Lee, Yoomi

    2010-01-01

    Only rarely do corticotroph pituitary tumors become invasive leading to symptoms caused by compression of cranial nerves and other local structures. When aggressive pituitary neuroendocrine tumors do develop, conventional treatment options are of limited success. A 50-year-old man developed a giant invasive corticotroph pituitary tumor 2 years after initial presentation. His tumor and symptoms failed to respond to maximal surgical, radio-surgical, radiation and medical therapy and a bilateral adrenalectomy was done. He subsequently developed rapid growth of his tumor leading to multiple cranial nerve deficits. He was administered salvage chemotherapy with capecitabine and temozolomide (CAPTEM), a novel oral chemotherapy regimen developed at our institution for treatment of neuroendocrine tumors. After two cycles of CAPTEM, his tumor markedly decreased in size and ACTH levels fell by almost 90%. Despite further decreases in ACTH levels, his tumor recurred after 5 months with increased avidity on PET scan suggesting a transformation to a more aggressive phenotype. Temozolomide had been reported to be effective against other pituitary tumors and this case adds to this literature demonstrating its use along with capecitabine (CAPTEM) against a corticotroph tumor. Further evaluation of the CAPTEM regimen in patients with pituitary neuroendocrine tumors which fail to respond to classic treatments is warranted. PMID:19960369

  13. The effects of drivers’ aggressive characteristics on traffic stability from a new car-following model

    NASA Astrophysics Data System (ADS)

    Peng, Guanghan; Qing, Li

    2016-06-01

    In this paper, a new car-following model is proposed by considering the drivers’ aggressive characteristics. The stable condition and the modified Korteweg-de Vries (mKdV) equation are obtained by the linear stability analysis and nonlinear analysis, which show that the drivers’ aggressive characteristics can improve the stability of traffic flow. Furthermore, the numerical results show that the drivers’ aggressive characteristics increase the stable region of traffic flow and can reproduce the evolution and propagation of small perturbation.

  14. 3D Silicon Microstructures: A New Tool for Evaluating Biological Aggressiveness of Tumor Cells.

    PubMed

    Mazzini, Giuliano; Carpignano, Francesca; Surdo, Salvatore; Aredia, Francesca; Panini, Nicolò; Torchio, Martina; Erba, Eugenio; Danova, Marco; Scovassi, Anna Ivana; Barillaro, Giuseppe; Merlo, Sabina

    2015-10-01

    In this work, silicon micromachined structures (SMS), consisting of arrays of 3- μ m-thick silicon walls separated by 50- μm-deep, 5- μ m-wide gaps, were applied to investigate the behavior of eight tumor cell lines, with different origins and biological aggressiveness, in a three-dimensional (3D) microenvironment. Several cell culture experiments were performed on 3D-SMS and cells grown on silicon were stained for fluorescence microscopy analyses. Most of the tumor cell lines recognized in the literature as highly aggressive (OVCAR-5, A375, MDA-MB-231, and RPMI-7951) exhibited a great ability to enter and colonize the narrow deep gaps of the SMS, whereas less aggressive cell lines (OVCAR-3, Capan-1, MCF7, and NCI-H2126) demonstrated less penetration capability and tended to remain on top of the SMS. Quantitative image analyses of several fluorescence microscopy fields of silicon samples were performed for automatic cell recognition and count, in order to quantify the fraction of cells inside the gaps, with respect to the total number of cells in the examined field. Our results show that higher fractions of cells in the gaps are obtained with more aggressive cell lines, thus supporting in a quantitative way the observation that the behavior of tumor cells on the 3D-SMS depends on their aggressiveness level.

  15. Vascular patterns provide therapeutic targets in aggressive neuroblastic tumors

    PubMed Central

    Tadeo, Irene; Bueno, Gloria; Berbegall, Ana P.; Fernández-Carrobles, M. Milagro; Castel, Victoria; García-Rojo, Marcial; Navarro, Samuel; Noguera, Rosa

    2016-01-01

    Angiogenesis is essential for tumor growth and metastasis, nevertheless, in NB, results between different studies on angiogenesis have yielded contradictory results. An image analysis tool was developed to characterize the density, size and shape of total blood vessels and vascular segments in 458 primary neuroblastic tumors contained in tissue microarrays. The results were correlated with clinical and biological features of known prognostic value and with risk of progression to establish histological vascular patterns associated with different degrees of malignancy. Total blood vessels were larger, more abundant and more irregularly-shaped in tumors of patients with associated poor prognostic factors than in the favorable cohort. Tumor capillaries were less abundant and sinusoids more abundant in the patient cohort with unfavorable prognostic factors. Additionally, size of post-capillaries & metarterioles as well as higher sinusoid density can be included as predictive factors for survival. These patterns may therefore help to provide more accurate pre-treatment risk stratification, and could provide candidate targets for novel therapies. PMID:26918726

  16. Expression Profiling of Primary and Metastatic Ovarian Tumors Reveals Differences Indicative of Aggressive Disease

    PubMed Central

    Brodsky, Alexander S.; Fischer, Andrew; Miller, Daniel H.; Vang, Souriya; MacLaughlan, Shannon; Wu, Hsin-Ta; Yu, Jovian; Steinhoff, Margaret; Collins, Colin; Smith, Peter J. S.; Raphael, Benjamin J.; Brard, Laurent

    2014-01-01

    The behavior and genetics of serous epithelial ovarian cancer (EOC) metastasis, the form of the disease lethal to patients, is poorly understood. The unique properties of metastases are critical to understand to improve treatments of the disease that remains in patients after debulking surgery. We sought to identify the genetic and phenotypic landscape of metastatic progression of EOC to understand how metastases compare to primary tumors. DNA copy number and mRNA expression differences between matched primary human tumors and omental metastases, collected at the same time during debulking surgery before chemotherapy, were measured using microarrays. qPCR and immunohistochemistry validated findings. Pathway analysis of mRNA expression revealed metastatic cancer cells are more proliferative and less apoptotic than primary tumors, perhaps explaining the aggressive nature of these lesions. Most cases had copy number aberrations (CNAs) that differed between primary and metastatic tumors, but we did not detect CNAs that are recurrent across cases. A six gene expression signature distinguishes primary from metastatic tumors and predicts overall survival in independent datasets. The genetic differences between primary and metastatic tumors, yet common expression changes, suggest that the major clone in metastases is not the same as in primary tumors, but the cancer cells adapt to the omentum similarly. Together, these data highlight how ovarian tumors develop into a distinct, more aggressive metastatic state that should be considered for therapy development. PMID:24732363

  17. Nerve Fibers in Breast Cancer Tissues Indicate Aggressive Tumor Progression

    PubMed Central

    Huang, Di; Su, Shicheng; Cui, Xiuying; Shen, Ximing; Zeng, Yunjie; Wu, Wei; Chen, Jianing; Chen, Fei; He, Chonghua; Liu, Jiang; Huang, Wei; Liu, Qiang; Su, Fengxi; Song, Erwei; Ouyang, Nengtai

    2014-01-01

    Abstract Emerging evidence has indicated nerve fibers as a marker in the progression of various types of cancers, such as pancreatic cancer and prostate cancer. However, whether nerve fibers are associated with breast cancer progression remains unclear. In this study, we evaluated the presence of nerve fibers in 352 breast cancer specimens and 83 benign breast tissue specimens including 43 cases of cystic fibrosis and 40 cases of fibroadenoma from 2 independent breast tumor center using immunohistochemical staining for specific peripheral nerve fiber markers. In all, nerve fibers were present in 130 out of 352 breast cancer tissue specimens, while none were detected in normal breast tissue specimens. Among 352 cases, we defined 239 cases from Sun Yat-Sen Memorial Hospital, Guangzhou, China, as the training set, and 113 cases from the First Affiliated Hospital of Shantou University, Guangdong, China, as the validation set. The thickness of tumor-involving nerve fibers is significantly correlated with poor differentiation, lymph node metastasis, high clinical staging, and triple negative subtype in breast cancer. More importantly, Cox multifactor analysis indicates that the thickness of tumor-involving nerve fibers is a previously unappreciated independent prognostic factors associated with shorter disease-free survival of breast cancer patients. Our findings are further validated by online Oncomine database. In conclusion, our results show that nerve fiber involvement in breast cancer is associated with progression of the malignancy and warrant further studies in the future. PMID:25501061

  18. The Influence of Neighborhood Characteristics and Parenting Practices on Academic Problems and Aggression Outcomes among Moderately to Highly Aggressive Children

    ERIC Educational Resources Information Center

    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…

  19. Differential Characteristics for Hyperactive Children High and Low on Aggression.

    ERIC Educational Resources Information Center

    Prinz, Ronald J.

    To determine which of several variables best predict aggression in hyperactive children, 38 hyperactive first-, second-, and third-graders were assessed for 12 consecutive school days on 11 behaviors associated with aggression. Behavioral items on the criterion measure, the Daily Behavior Checklist, were summed and then averaged over the 12 days…

  20. Impact of macrophages on tumor growth characteristics in a murine ocular tumor model.

    PubMed

    Stei, Marta M; Loeffler, Karin U; Kurts, Christian; Hoeller, Tobias; Pfarrer, Christiane; Holz, Frank G; Herwig-Carl, Martina C

    2016-10-01

    Tumor associated macrophages (TAM), mean vascular density (MVD), PAS positive extravascular matrix patterns, and advanced patients' age are associated with a poor prognosis in uveal melanoma. These correlations may be influenced by M2 macrophages and their cytokine expression pattern. Thus, the effect of TAM and their characteristic cytokines on histologic tumor growth characteristics were studied under the influence of age. Ninety five CX3CR1(+/GFP) mice (young 8-12weeks, old 10-12months) received an intravitreal injection of 1 × 10(5) HCmel12 melanoma cells. Subgroups were either systemically macrophage-depleted by Clodronate liposomes (n = 23) or received melanoma cells, which were pre-incubated with the supernatant of M1- or M2-polarized macrophages (n = 26). Eyes were processed histologically/immunohistochemically (n = 75), or for flow cytometry (n = 20) to analyze tumor size, mean vascular density (MVD), extravascular matrix patterns, extracellular matrix (ECM) and the presence/polarization of TAM. Prognostically significant extravascular matrix patterns (parallels with cross-linkings, loops, networks) were found more frequently in tumors of untreated old compared to tumors of untreated young mice (p = 0.024); as well as in tumors of untreated mice compared to tumors of macrophage-depleted mice (p = 0.014). Independent from age, M2-conditioned tumors showed more TAM (p = 0.001), increased collagen IV levels (p = 0.024) and a higher MVD (p = 0.02) than M1-conditioned tumors. Flow cytometry revealed a larger proportion of M2-macrophages in old than in young mice. The results indicate that TAM and their cytokines appear to be responsible for a more aggressive tumor phenotype. Tumor favoring and pro-angiogenic effects can be directly attributed to a M2-dominated tumor microenvironment rather than to age-dependent factors alone. However, an aged immunoprofile with an increased number of M2-macrophages may provide a tumor-favoring basis

  1. Aggressive Calcifying Epithelial Odontogenic Tumor of the Maxillary Sinus with Extraosseous Oral Mucosal Involvement: A Case Report

    PubMed Central

    Rani, Vidya; Masthan, Mahaboob Kadar; Aravindha, Babu; Leena, Sankari

    2016-01-01

    Calcifying epithelial odontogenic tumors are benign odontogenic neoplasms whose occurrence in the maxillary sinus is rare. Maxillary tumors tend to be locally aggressive and may rapidly involve the surrounding vital structures. We report a case of a large calcifying epithelial odontogenic tumor of the maxilla, involving the maxillary sinus in a 48-year-old woman. The tumor was largely intraosseous. In the canine and first premolar regions, the loss of bone could be palpated but the oral mucosa appeared normal. Histologically, the tumor tissue could be seen in the connective tissue below the oral epithelium. The most significant finding was the presence of an intraosseous tumor with an extraosseous involvement in a single tumor, indicating aggressive behavior and warranting aggressive treatment. In this article, we discuss the rare presentation of the tumor and its radiological appearance and histological features. We also highlight the importance of a detailed histopathological examination of the excised specimen. PMID:26989286

  2. 'Salvage Treatment' of Aggressive Giant Cell Tumor of Bones with Denosumab

    PubMed Central

    Vaishya, Raju; Vijay, Vipul

    2015-01-01

    Giant cell tumor of the bone (GCTB) presents as a lytic lesion of epiphyseometaphyseal regions of the long bones usually during the second to the fourth decade with female predilection. Histologically, they are formed of neoplastic mononuclear cells with a higher receptor activator of nuclear factor kappa-B ligand (RANKL) expression responsible for the aggressive osteolytic nature of the tumour. RANKL helps in the formation and functioning of osteoclasts. A newer molecule, Denosumab, is a monoclonal antibody directed against RANKL and thus prevents the formation and function of osteoclasts. Management of refractory, multicentric, recurrent, or metastatic GCTB remains challenging as achieving a tumor-free margin surgically is not always possible. Denosumab may play a crucial role, especially in the management of such difficult lesions. We present three cases of locally aggressive GCTB (involving proximal humerus, sacrum, and proximal femur) that were treated and responded very well to Denosumab therapy. PMID:26251767

  3. Metabolic coupling in urothelial bladder cancer compartments and its correlation to tumor aggressiveness.

    PubMed

    Afonso, Julieta; Santos, Lúcio L; Morais, António; Amaro, Teresina; Longatto-Filho, Adhemar; Baltazar, Fátima

    2016-01-01

    Monocarboxylate transporters (MCTs) are vital for intracellular pH homeostasis by extruding lactate from highly glycolytic cells. These molecules are key players of the metabolic reprogramming of cancer cells, and evidence indicates a potential contribution in urothelial bladder cancer (UBC) aggressiveness and chemoresistance. However, the specific role of MCTs in the metabolic compartmentalization within bladder tumors, namely their preponderance on the tumor stroma, remains to be elucidated. Thus, we evaluated the immunoexpression of MCTs in the different compartments of UBC tissue samples (n = 111), assessing the correlations among them and with the clinical and prognostic parameters. A significant decrease in positivity for MCT1 and MCT4 occurred from normoxic toward hypoxic regions. Significant associations were found between the expression of MCT4 in hypoxic tumor cells and in the tumor stroma. MCT1 staining in normoxic tumor areas, and MCT4 staining in hypoxic regions, in the tumor stroma and in the blood vessels were significantly associated with UBC aggressiveness. MCT4 concomitant positivity in hypoxic tumor cells and in the tumor stroma, as well as positivity in each of these regions concomitant with MCT1 positivity in normoxic tumor cells, was significantly associated with an unfavourable clinicopathological profile, and predicted lower overall survival rates among patients receiving platinum-based chemotherapy. Our results point to the existence of a multi-compartment metabolic model in UBC, providing evidence of a metabolic coupling between catabolic stromal and cancer cells' compartments, and the anabolic cancer cells. It is urgent to further explore the involvement of this metabolic coupling in UBC progression and chemoresistance. PMID:26636903

  4. Malignant thyroid teratoma: report of an aggressive tumor in a 64-year-old man.

    PubMed

    Vilallonga, R; Zafon, C; Ruiz-Marcellan, C; Obiols, G; Fort, J M; Baena, J A; Villanueva, B; Garcia, A; Sobrinho-Simões, M

    2013-09-01

    Malignant teratoma of the thyroid is a rare and aggressive tumor, frequent in children than in adults. Histologically, thyroid teratomas usually show a predominance of a neuroectodermal component. Mature cartilage and bone may be present. We present the case of primary malignant teratoma of the thyroid in a 64-year-old man. Histologically, the tumor displayed a predominant neuroectodermal component. The diagnosis was confirmed by immunohistochemistry. The patient underwent a radical thyroidectomy with central neck dissection as primary treatment and radioiodine treatment afterwards. The patient had local and distant recurrence. A second surgery was performed with poor results and the patient died 3 months afterwards.

  5. Do Friends' Characteristics Moderate the Prospective Links between Peer Victimization and Reactive and Proactive Aggression?

    ERIC Educational Resources Information Center

    Lamarche, Veronique; Brendgen, Mara; Boivin, Michel; Vitaro, Frank; Dionne, Ginette; Perusse, Daniel

    2007-01-01

    This study examined (a) the predictive link between peer victimization and children's reactive and proactive aggression, and (b) the potential moderating effect of reciprocal friends' reactive and proactive aggression in this context. The study also examined whether these potential moderating effects of friends' characteristics were stronger with…

  6. Biallelic BRCA2 Mutations Shape the Somatic Mutational Landscape of Aggressive Prostate Tumors.

    PubMed

    Decker, Brennan; Karyadi, Danielle M; Davis, Brian W; Karlins, Eric; Tillmans, Lori S; Stanford, Janet L; Thibodeau, Stephen N; Ostrander, Elaine A

    2016-05-01

    To identify clinically important molecular subtypes of prostate cancer (PCa), we characterized the somatic landscape of aggressive tumors via deep, whole-genome sequencing. In our discovery set of ten tumor/normal subject pairs with Gleason scores of 8-10 at diagnosis, coordinated analysis of germline and somatic variants, including single-nucleotide variants, indels, and structural variants, revealed biallelic BRCA2 disruptions in a subset of samples. Compared to the other samples, the PCa BRCA2-deficient tumors exhibited a complex and highly specific mutation signature, featuring a 2.88-fold increased somatic mutation rate, depletion of context-specific C>T substitutions, and an enrichment for deletions, especially those longer than 10 bp. We next performed a BRCA2 deficiency-targeted reanalysis of 150 metastatic PCa tumors, and each of the 18 BRCA2-mutated samples recapitulated the BRCA2 deficiency-associated mutation signature, underscoring the potent influence of these lesions on somatic mutagenesis and tumor evolution. Among all 21 individuals with BRCA2-deficient tumors, only about half carried deleterious germline alleles. Importantly, the somatic mutation signature in tumors with one germline and one somatic risk allele was indistinguishable from those with purely somatic mutations. Our observations clearly demonstrate that BRCA2-disrupted tumors represent a unique and clinically relevant molecular subtype of aggressive PCa, highlighting both the promise and utility of this mutation signature as a prognostic and treatment-selection biomarker. Further, any test designed to leverage BRCA2 status as a biomarker for PCa must consider both germline and somatic mutations and all types of deleterious mutations.

  7. Increased beta-catenin protein and somatic APC mutations in sporadic aggressive fibromatoses (desmoid tumors).

    PubMed

    Alman, B A; Li, C; Pajerski, M E; Diaz-Cano, S; Wolfe, H J

    1997-08-01

    Sporadic aggressive fibromatosis (also called desmoid tumor) is a monoclonal proliferation of spindle (fibrocyte-like) cells that is locally invasive but does not metastasize. A similarity to abdominal fibromatoses (desmoids) in familial adenomatous polyposis and a cytogenetic study showing partial deletion of 5q in a subset of aggressive fibromatoses suggests that the adenomatous polyposis coli (APC) gene plays a role in its pathogenesis. APC helps regulate the cellular level of beta-catenin, which is a downstream mediator in Wnt (Wingless) signaling. beta-Catenin has a nuclear function (binds transcription factors) and a cell membrane function (is a component of epithelial cell adherens junctions). Six cases of aggressive fibromatosis of the extremities from patients without familial adenomatous polyposis, or a family history of colon cancer, were studied. Immunohistochemistry, using carboxy and amino terminus antibodies to APC, and DNA sequencing showed that three of the six contained an APC-truncating mutation, whereas normal tissues did not contain a mutation. Western blot and Northern dot blot showed that all six tumors had a higher level of beta-catenin protein than surrounding normal tissues, despite containing similar levels of beta-catenin mRNA. Immunohistochemistry localized beta-catenin throughout the cell in tumor tissues, although it localized more to the periphery in cells from normal tissues. Reverse transcription polymerase chain reaction showed that the tumors expressed N-cadherin but not E-cadherin (a pattern of expression of proteins making up adherens junctions similar to fibrocytes), suggesting that the specific adherens junctions present in epithelial cells are not necessary for beta-catenin function. Increased beta-catenin may cause the growth advantage of cells in this tumor through a nuclear mechanism. The increased protein level, relative to the RNA level, suggests that beta-catenin is degraded at a lower rate compared with normal tissues

  8. Increased beta-catenin protein and somatic APC mutations in sporadic aggressive fibromatoses (desmoid tumors).

    PubMed Central

    Alman, B. A.; Li, C.; Pajerski, M. E.; Diaz-Cano, S.; Wolfe, H. J.

    1997-01-01

    Sporadic aggressive fibromatosis (also called desmoid tumor) is a monoclonal proliferation of spindle (fibrocyte-like) cells that is locally invasive but does not metastasize. A similarity to abdominal fibromatoses (desmoids) in familial adenomatous polyposis and a cytogenetic study showing partial deletion of 5q in a subset of aggressive fibromatoses suggests that the adenomatous polyposis coli (APC) gene plays a role in its pathogenesis. APC helps regulate the cellular level of beta-catenin, which is a downstream mediator in Wnt (Wingless) signaling. beta-Catenin has a nuclear function (binds transcription factors) and a cell membrane function (is a component of epithelial cell adherens junctions). Six cases of aggressive fibromatosis of the extremities from patients without familial adenomatous polyposis, or a family history of colon cancer, were studied. Immunohistochemistry, using carboxy and amino terminus antibodies to APC, and DNA sequencing showed that three of the six contained an APC-truncating mutation, whereas normal tissues did not contain a mutation. Western blot and Northern dot blot showed that all six tumors had a higher level of beta-catenin protein than surrounding normal tissues, despite containing similar levels of beta-catenin mRNA. Immunohistochemistry localized beta-catenin throughout the cell in tumor tissues, although it localized more to the periphery in cells from normal tissues. Reverse transcription polymerase chain reaction showed that the tumors expressed N-cadherin but not E-cadherin (a pattern of expression of proteins making up adherens junctions similar to fibrocytes), suggesting that the specific adherens junctions present in epithelial cells are not necessary for beta-catenin function. Increased beta-catenin may cause the growth advantage of cells in this tumor through a nuclear mechanism. The increased protein level, relative to the RNA level, suggests that beta-catenin is degraded at a lower rate compared with normal tissues

  9. Diffusion characteristics of pediatric pineal tumors

    PubMed Central

    Whitehead, Matthew T; Siddiqui, Adeel; Klimo, Paul; Boop, Frederick A

    2015-01-01

    Background Diffusion weighted imaging (DWI) has been shown to be helpful in characterizing tumor cellularity, and predicting histology. Several works have evaluated this technique for pineal tumors; however studies to date have not focused on pediatric pineal tumors. Objective We evaluated the diffusion characteristics of pediatric pineal tumors to confirm if patterns seen in studies using mixed pediatric and adult populations remain valid. Materials and methods This retrospective study was performed after Institutional Review Board approval. We retrospectively evaluated all patients 18 years of age and younger with pineal tumors from a single institution where preoperative diffusion weighted imaging as well as histologic characterization was available. Results Twenty patients (13 male, 7 female) with pineal tumors were identified: seven with pineoblastoma, four with Primitive Neuroectodermal Tumor (PNET), two with other pineal tumors, and seven with germ cell tumors including two germinomas, three teratomas, and one mixed germinoma-teratoma. The mean apparent diffusion coefficient (ADC) values in pineoblastoma (544 ± 65 × 10–6 mm2/s) and pineoblastoma/PNET (595 ± 144 × 10–6 mm2/s) was lower than that of the germ cell tumors (1284 ± 334 × 10–6 mm2/s; p < 0.0001 vs pineoblastoma). One highly cellular germinoma had an ADC value of 694 × 10–6 mm2/s. Conclusion ADC values can aid in differentiation of pineoblastoma/PNET from germ cell tumors in a population of children with pineal masses. PMID:25963154

  10. Oncogenic Properties of Apoptotic Tumor Cells in Aggressive B Cell Lymphoma

    PubMed Central

    Ford, Catriona A.; Petrova, Sofia; Pound, John D.; Voss, Jorine J.L.P.; Melville, Lynsey; Paterson, Margaret; Farnworth, Sarah L.; Gallimore, Awen M.; Cuff, Simone; Wheadon, Helen; Dobbin, Edwina; Ogden, Carol Anne; Dumitriu, Ingrid E.; Dunbar, Donald R.; Murray, Paul G.; Ruckerl, Dominik; Allen, Judith E.; Hume, David A.; van Rooijen, Nico; Goodlad, John R.; Freeman, Tom C.; Gregory, Christopher D.

    2015-01-01

    Summary Background Cells undergoing apoptosis are known to modulate their tissue microenvironments. By acting on phagocytes, notably macrophages, apoptotic cells inhibit immunological and inflammatory responses and promote trophic signaling pathways. Paradoxically, because of their potential to cause death of tumor cells and thereby militate against malignant disease progression, both apoptosis and tumor-associated macrophages (TAMs) are often associated with poor prognosis in cancer. We hypothesized that, in progression of malignant disease, constitutive loss of a fraction of the tumor cell population through apoptosis could yield tumor-promoting effects. Results Here, we demonstrate that apoptotic tumor cells promote coordinated tumor growth, angiogenesis, and accumulation of TAMs in aggressive B cell lymphomas. Through unbiased “in situ transcriptomics” analysis—gene expression profiling of laser-captured TAMs to establish their activation signature in situ—we show that these cells are activated to signal via multiple tumor-promoting reparatory, trophic, angiogenic, tissue remodeling, and anti-inflammatory pathways. Our results also suggest that apoptotic lymphoma cells help drive this signature. Furthermore, we demonstrate that, upon induction of apoptosis, lymphoma cells not only activate expression of the tumor-promoting matrix metalloproteinases MMP2 and MMP12 in macrophages but also express and process these MMPs directly. Finally, using a model of malignant melanoma, we show that the oncogenic potential of apoptotic tumor cells extends beyond lymphoma. Conclusions In addition to its profound tumor-suppressive role, apoptosis can potentiate cancer progression. These results have important implications for understanding the fundamental biology of cell death, its roles in malignant disease, and the broader consequences of apoptosis-inducing anti-cancer therapy. PMID:25702581

  11. Radiation therapy for aggressive fibromatosis (desmoid tumors): Results of a national Patterns of Care Study

    SciTech Connect

    Micke, Oliver . E-mail: omicke@benign-news.de; Seegenschmiedt, M. Heinrich

    2005-03-01

    Purpose: After a general Patterns of Care Study (PCS) the German Cooperative Group on Radiotherapy for Benign Diseases (GCG-BD) initiated a multicenter cohort study to analyze the radiation therapy practice for aggressive fibromatosis. Methods and materials: In 2002 a PCS was conducted in all German radiotherapy (RT) institutions by mailing a standardized structured questionnaire, to assess patients accrual, number, pretreatment, treatment indications, RT, and target volume concepts for irradiation in aggressive fibromatosis. In addition, the treatment outcome of individual patients was evaluated. The PCS was structured and analyzed according to the model for quality assessment by Donabedian in three major components: structure, process, and outcome evaluation. Results: A total of 101 institutions returned the questionnaire: 52.7% reported satisfactory clinical data and experience for inclusion in this analysis. A total accrual rate of 278 patients per year was reported with median number of 2 cases (1-7 cases) per institution. Satisfactory data for a long-term clinical evaluation was reported for 345 patients from 19 different institutions. The applied total doses ranged between 36 and 65 Gy (median, 60 Gy). The local control rate was 81.4% in primary RT for unresectable tumors and 79.6% in postoperative RT. No acute or late radiation toxicities > Grade 2 (RTOG) were observed. No clear dose-response relationship could be established, but there was a tendency toward a lower local control rate in patients with a higher number of operative procedures before RT and patients treated for recurrent aggressive fibromatosis. Conclusions: This study comprises the largest database of cases reported for RT in aggressive fibromatosis. Radiotherapy provides a high local control rate in the postoperative setting and in unresectable tumors. This PCS may serve as a starting point for a national or international prospective multicenter study or registry, or both.

  12. May bone cement be used to treat benign aggressive bone tumors of the feet with confidence?

    PubMed

    Özer, Devrim; Er, Turgay; Aycan, Osman Emre; Öke, Ramadan; Coşkun, Mehmet; Kabukçuoğlu, Yavuz Selim

    2014-03-01

    Using bone cement for the reconstruction of defects created after curettage of benign aggressive bone tumors is among acceptable methods. The study aimed to assess the effect of bone cement used in aggressive bone tumors in the feet on the function of the feet. Five patients were reviewed. They were treated between 2004 and 2010. Three cases were female and two male. Their age ranged from 16 to 55 with an average of 34.8. Follow up period ranged from 14 to 86 months with an average of 34. Two cases were giant cell tumor of bone located in calcaneus and 3 were solid variant aneurysmal bone cyst located in talus, navicular and first proximal phalanx. None had any previous treatment. A biopsy was done in all cases. Treatment was curettage, high speed burring (except phalanx case), and filling the cavity with bone cement. The case located in talus recurred and re-operated 1 year later doing the same procedure. Final evaluation included physical examination, X-ray and Maryland Foot Score. No recurrence was present in the final evaluation. No problems were detected related to bone cement. Maryland Foot Scores ranged 84-100, average of 94. Cement integrity was not disturbed. The procedure is found not to effect foot functions adversely.

  13. Clinically aggressive primary solid pseudopapillary tumor of the ovary in a 45-year-old woman

    PubMed Central

    Syriac, Susanna; Kesterson, Joshua; Izevbaye, Iyare; de Mesy Bentley, Karen L.; Lele, Shashikant; Mhawech-Fauceglia, Paulette

    2016-01-01

    We report the first case of primary solid pseudopapillary tumor of the ovary with aggressive behavior and fatal outcome in a 45-year-old woman. The patient presented with weight loss, decrease of appetite, and abdominal bloating for the last several weeks. Computed tomography scan revealed an ovarian mass, omental caking, complex ascites, and 2 hepatic lesions. The pancreas was unremarkable. Grossly, the ovarian mass showed severe capsular adhesion, and the cut surface was cystic and solid. On histologic examination, the tumor was composed of diffuse solid pseudopapillary and pseudocystic patterns. The neoplastic cells were uniform and round with very dispersed chromatin. The cytoplasm was faintly pink. There was mild atypia, but the mitotic rate was as high as 62 per 50 high-power field, and the Ki-67 was elevated at 20%. The tumor exhibited severe necrosis. Numerous foci of lymphovascular invasion were also seen. The tumor cells were positive for cytokeratin (focal) and for β-catenin (cytoplasmic and nuclear patterns). They were negative for chromogranin, synaptophysin, thyroglobulin, calcitonin, hepatocyte-paraffin 1, epithelial membrane antigen, calretinin, and α-inhibin. Electron microscopic study revealed nests of tumor cells with oval nuclei. The cytoplasm contained numerous pleomorphic mitochondria interspersed among short strands of rough endoplasmic reticulum. The tumor involved the fallopian tube, omentum, cul-de-sac, and abdominal wall. The pelvic washing was also positive for tumor cells. Despite chemotherapy, the patient's condition had worsened, and she died of her disease 8 months after the initial diagnosis. We discuss the differential diagnosis of this tumor and the hypothesis of its origin. PMID:21778097

  14. Expression of EGFR Under Tumor Hypoxia: Identification of a Subpopulation of Tumor Cells Responsible for Aggressiveness and Treatment Resistance

    SciTech Connect

    Hoogsteen, Ilse J.; Marres, Henri A.M.; Hoogen, Franciscus J.A. van den

    2012-11-01

    Purpose: Overexpression of epidermal growth factor receptor (EGFR) and tumor hypoxia have been shown to correlate with worse outcome in several types of cancer including head-and-neck squamous cell carcinoma. Little is known about the combination and possible interactions between the two phenomena. Methods and Materials: In this study, 45 cases of histologically confirmed squamous cell carcinomas of the head and neck were analyzed. All patients received intravenous infusions of the exogenous hypoxia marker pimonidazole prior to biopsy. Presence of EGFR, pimonidazole binding, and colocalization between EGFR and tumor hypoxia were examined using immunohistochemistry. Results: Of all biopsies examined, respectively, 91% and 60% demonstrated EGFR- and pimonidazole-positive areas. A weak but significant association was found between the hypoxic fractions of pimonidazole (HFpimo) and EGFR fractions (F-EGFR) and between F-EGFR and relative vascular area. Various degrees of colocalization between hypoxia and EGFR were found, increasing with distance from the vasculature. A high fraction of EGFR was correlated with better disease-free and metastasis-free survival, whereas a high degree of colocalization correlated with poor outcome. Conclusions: Colocalization of hypoxia and EGFR was demonstrated in head-and-neck squamous cell carcinomas, predominantly at longer distances from vessels. A large amount of colocalization was associated with poor outcome, which points to a survival advantage of hypoxic cells that are also able to express EGFR. This subpopulation of tumor cells might be indicative of tumor aggressiveness and be partly responsible for treatment resistance.

  15. Tumor associated macrophage expressing CD204 is associated with tumor aggressiveness of esophageal squamous cell carcinoma.

    PubMed

    Shigeoka, Manabu; Urakawa, Naoki; Nakamura, Tetsu; Nishio, Mari; Watajima, Taketo; Kuroda, Daisuke; Komori, Takahide; Kakeji, Yoshihiro; Semba, Shuho; Yokozaki, Hiroshi

    2013-08-01

    Tumor associated macrophages (TAMs) are the most abundant cancer stromal cells educated by tumor microenvironment to acquire trophic functions facilitating angiogenesis, matrix breakdown and cancer cell motility. Tumor associated macrophages have anti-inflammatory properties or "alternatively" activated (M2) phenotype expressing CD204 and/or CD163. To know the role of TAMs in the growth and progression of esophageal squamous cell carcinomas (ESCCs), we calculated intratumoral CD204, CD163 or CD68 expressing macrophage count (MϕC) and CD34-positive microvessel density (MVD) by immunohistochemistry in 70 cases of surgically resected ESCCs and compared them with the clinicopathological factors and prognosis of patients. MϕC had positive linear association with MVD. High CD204(+) MϕC were significantly correlated with more malignant phenotypes including depth of tumor invasion, lymph and blood vessel invasion, lymph node metastasis as well as clinical stages. On the other hand, CD163(+) MϕC did not associate with these clinicopathological factors with the exception of depth of tumor invasion and blood vessel invasion. Patients with high CD204(+) MϕC ESCCs showed poor disease-free survival (P = 0.021). Conditioned media of five ESCC cell lines (TE-8, -9, -10, -11 and -15) induced mRNA as well as protein expression of CD204 but not of CD163 with upregulation of vascular endothelial growth factor-A mRNA in TPA treated human acute monocytic leukemia cell line THP-1. These results overall indicate that CD204 is a useful marker for TAMs contributing to the angiogenesis, progression and prognosis of ESCCs whose specific tumor microenvironment may educate macrophages to be CD204(+) M2 TAMs.

  16. An aggressive solitary fibrous tumor with evidence of malignancy: a rare case report.

    PubMed

    Vimi, S; Punnya, V A; Kaveri, H; Rekha, K

    2008-09-01

    Solitary fibrous tumor (SFT) is rare mesenchymal neoplasm that has been originally and most often documented in the pleura. Recently, the ubiquitous nature of the SFT has been recognized with reports of involvement of numerous sites all over the body, i.e, upper respiratory tract, breast, somatic tissue, mediastinum, head, and neck, etc. The diagnosis of SFT still remains an enigma in our field. Furthermore, malignant SFT is extremely rare and only two cases have been reported in the oral cavity till date. Here, we present a rare case report of an aggressive solitary fibrous tumor which presented as a palatal mass and extended throughout the middle cranial fossa and exhibited features of malignancy.

  17. Temozolomide Therapy for Aggressive Pituitary Tumors: Results in a Small Series of Patients from Argentina

    PubMed Central

    Bruno, Oscar D.; Juárez-Allen, Lea; Christiansen, Silvia B.; Manavela, Marcos; Danilowicz, Karina; Vigovich, Carlos; Gómez, Reynaldo M.

    2015-01-01

    We evaluated results of temozolomide (TMZ) therapy in six patients, aged 34–78 years, presenting aggressive pituitary tumors. In all the patients tested O6-methylguanine-DNA methyltransferase (MGMT) immunoexpression in surgical specimens was absent. Patients received temozolomide 140–320 mg/day for 5 days monthly for at least 3 months. In two patients minimum time for evaluation could not be reached because of death in a 76-year-old man with a malignant prolactinoma and of severe neutro-thrombopenia in a 47-year-old woman with nonfunctioning pituitary adenoma. In two patients (a 34-year-old acromegalic woman and a 39-year-old woman with Nelson's syndrome) no response was observed after 4 and 6 months, respectively, and the treatment was stopped. Conversely, two 52- and 42-year-old women with Cushing's disease had long-term total clinical and radiological remissions which persisted after stopping temozolomide. We conclude that TMZ therapy may be of variable efficacy depending on—until now—incompletely understood factors. Cooperative work on a greater number of cases of aggressive pituitary tumors should be crucial to establish the indications, doses, and duration of temozolomide administration. PMID:26106414

  18. Prolactinoma ErbB receptor expression and targeted therapy for aggressive tumors.

    PubMed

    Cooper, Odelia; Mamelak, Adam; Bannykh, Serguei; Carmichael, John; Bonert, Vivien; Lim, Stephen; Cook-Wiens, Galen; Ben-Shlomo, Anat

    2014-06-01

    As ErbB signaling is a determinant of prolactin synthesis, role of ErbB receptors was tested for prolactinoma outcomes and therapy. The objective of this study was to characterize ErbB receptor expression in prolactinomas and then perform a pilot study treating resistant prolactinomas with a targeted tyrosine kinase inhibitor (TKI). Retrospective analysis of prolactinomas and pilot study for dopamine agonist resistant prolactinomas in tertiary referral center. We performed immunofluorescent staining of a tissue array of 29 resected prolactinoma tissues for EGFR, ErbB2, ErbB3, and ErbB4 correlated with clinical features. Two patients with aggressive resistant prolactinomas enrolled and completed trial. They received lapatinib 1,250 mg daily for 6 months with tumor and hormone assessments. Main outcome measures were positive tumor staining of respective ErbB receptors, therapeutic reduction of prolactin levels and tumor shrinkage. Treated PRL levels and tumor volumes were suppressed in both subjects treated with TKI. EGFR expression was positive in 82 % of adenomas, ErbB2 in 92 %, ErbB3 in 25 %, and ErbB4 in 71 %, with ErbB2 score > EGFR > ErbB4 > ErbB3. Higher ErbB3 expression was associated with optic chiasm compression (p = 0.03), suprasellar extension (p = 0.04), and carotid artery encasement (p = 0.01). Higher DA response rates were observed in tumors with higher ErbB3 expression. Prolactinoma expression of specific ErbB receptors is associated with tumor invasion, symptoms, and response to dopamine agonists. Targeting ErbB receptors may be effective therapy in patients with resistant prolactinomas.

  19. The effects of drivers’ aggressive characteristics on traffic stability from a new car-following model

    NASA Astrophysics Data System (ADS)

    Peng, Guanghan; Qing, Li

    2016-06-01

    In this paper, a new car-following model is proposed by considering the drivers’ aggressive characteristics. The stable condition and the modified Korteweg-de Vries (mKdV) equation are obtained by the linear stability analysis and nonlinear analysis, which show that the drivers’ aggressive characteristics can improve the stability of traffic flow. Furthermore, the numerical results show that the drivers’ aggressive characteristics increase the stable region of traffic flow and can reproduce the evolution and propagation of small perturbation.

  20. Pancoast tumors: characteristics and preoperative assessment

    PubMed Central

    Panagopoulos, Nikolaos; Leivaditis, Vasilios; Koletsis, Efstratios; Prokakis, Christos; Alexopoulos, Panagiotis; Baltayiannis, Nikolaos; Hatzimichalis, Antonios; Tsakiridis, Kosmas; Zarogoulidis, Konstantinos; Katsikogiannis, Nikolaos; Kougioumtzi, Ioanna; Machairiotis, Nikolaos; Tsiouda, Theodora; Kesisis, Georgios; Siminelakis, Stavros; Madesis, Athanasios; Dougenis, Dimitrios

    2014-01-01

    Superior sulcus tumors (SSTs), or as otherwise known Pancoast tumors, make up a clinically unique and challenging subset of non-small cell carcinoma of the lung (NSCLC). Although the outcome of patients with this disease has traditionally been poor, recent developments have contributed to a significant improvement in prognosis of SST patients. The combination of severe and unrelenting shoulder and arm pain along the distribution of the eighth cervical and first and second thoracic nerve trunks, Horner’s syndrome (ptosis, miosis, and anhidrosis) and atrophy of the intrinsic hand muscles comprises a clinical entity named as “Pancoast-Tobias syndrome”. Apart NSCLC, other lesions may, although less frequently, result in Pancoast syndrome. In the current review we will present the main characteristics of the disease and focus on the preoperative assessment. PMID:24672686

  1. Aggressive CD34-positive fibrous scalp lesion of childhood: extrapulmonary solitary fibrous tumor.

    PubMed

    Ramdial, P K; Madaree, A

    2001-01-01

    Although solitary fibrous tumor (SFT) was originally described as a pleural tumor, an increasing number of extrapleural sites of SFTs have been documented. This has been attributed not only to the heightened awareness of the spectrum of histopathological features that characterizes SFTs but also to the recognition of the role of CD34 immunostaining in soft tissue tumors in general, and in SFTs in particular. Despite the large number of documented extrapleural SFTs in adults, cranial SFTs are rare, having been documented in the meninges, scalp, and infratemporal fossa. Extrapleural SFTs are, to date, an unrecognized entity in children. We document an aggressive fibrous scalp lesion in a 30-month-old female child that demonstrated features common to benign cranial fasciitis and SFT. However, based on bright, diffuse CD34 antigen immunopositivity, a diagnosis of SFT was made. The need to include the CD34 antigen stain in a panel of immunohistochemical markers used to assess spindle cell lesions of childhood is emphasized.

  2. Sortilin is associated with breast cancer aggressiveness and contributes to tumor cell adhesion and invasion

    PubMed Central

    Roselli, Séverine; Pundavela, Jay; Demont, Yohann; Faulkner, Sam; Keene, Sheridan; Attia, John; Jiang, Chen Chen; Zhang, Xu Dong; Walker, Marjorie M.; Hondermarck, Hubert

    2015-01-01

    The neuronal membrane protein sortilin has been reported in a few cancer cell lines, but its expression and impact in human tumors is unclear. In this study, sortilin was analyzed by immunohistochemistry in a series of 318 clinically annotated breast cancers and 53 normal breast tissues. Sortilin was detected in epithelial cells, with increased levels in cancers, as compared to normal tissues (p = 0.0088). It was found in 79% of invasive ductal carcinomas and 54% of invasive lobular carcinomas (p < 0.0001). There was an association between sortilin expression and lymph node involvement (p = 0.0093), suggesting a relationship with metastatic potential. In cell culture, sortilin levels were higher in cancer cell lines compared to non-tumorigenic breast epithelial cells and siRNA knockdown of sortilin inhibited cancer cell adhesion, while proliferation and apoptosis were not affected. Breast cancer cell migration and invasion were also inhibited by sortilin knockdown, with a decrease in focal adhesion kinase and SRC phosphorylation. In conclusion, sortilin participates in breast tumor aggressiveness and may constitute a new therapeutic target against tumor cell invasion. PMID:25871389

  3. GLI1 Transcription Factor Affects Tumor Aggressiveness in Patients With Papillary Thyroid Cancers.

    PubMed

    Lee, Jandee; Jeong, Seonhyang; Lee, Cho Rok; Ku, Cheol Ryong; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Shin, Dong Yeob; Chung, Woong Youn; Lee, Eun Jig; Jo, Young Suk

    2015-06-01

    A significant proportion of patients with papillary thyroid cancer (PTC) present with extrathyroidal extension (ETE) and lymph node metastasis (LNM). However, the molecular mechanism of tumor invasiveness in PTC remains to be elucidated. The aim of this study is to understand the role of Hedgehog (Hh) signaling in tumor aggressiveness in patients with PTC. Subjects were patients who underwent thyroidectomy from 2012 to 2013 in a single institution. Frozen or paraffin-embedded tumor tissues with contralateral-matched normal thyroid tissues were collected. Hh signaling activity was analyzed by quantitative RT-PCR (qRT-PCR) and immunohistochemical (IHC) staining. Datasets from Gene Expression Omnibus (GEO) (National Center for Biotechnology Information) were subjected to Gene Set Enrichment Analysis (GSEA). BRAFT1799A and telomerase reverse transcriptase promoter mutation C228T were analyzed by direct sequencing. Among 137 patients with PTC, glioma-associated oncogene homolog 1 (GLI1) group III (patients in whom the ratio of GLI1 messenger ribonucleic acid (mRNA) level in tumor tissue to GLI1 mRNA level in matched normal tissue was in the upper third of the subject population) had elevated risk for ETE (odds ratio [OR] 4.381, 95% confidence interval [CI] 1.414-13.569, P = 0.01) and LNM (OR 5.627, 95% CI 1.674-18.913, P = 0.005). Glioma-associated oncogene homolog 2 (GLI2) group III also had elevated risk for ETE (OR 4.152, 95% CI 1.292-13.342, P = 0.017) and LNM (OR 3.924, 95% CI 1.097-14.042, P = 0.036). GSEA suggested that higher GLI1 expression is associated with expression of the KEGG gene set related to axon guidance (P = 0.031, false discovery rate < 0.05), as verified by qRT-PCR and IHC staining in our subjects.GLI1 and GLI2 expressions were clearly related to aggressive clinicopathological features and aberrant activation of GLI1 involved in the axon guidance pathway. These results may contribute to development of new prognostic markers

  4. GLI1 Transcription Factor Affects Tumor Aggressiveness in Patients With Papillary Thyroid Cancers

    PubMed Central

    Lee, Jandee; Jeong, Seonhyang; Lee, Cho Rok; Ku, Cheol Ryong; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Shin, Dong Yeob; Chung, Woong Youn; Lee, Eun Jig; Jo, Young Suk

    2015-01-01

    Abstract A significant proportion of patients with papillary thyroid cancer (PTC) present with extrathyroidal extension (ETE) and lymph node metastasis (LNM). However, the molecular mechanism of tumor invasiveness in PTC remains to be elucidated. The aim of this study is to understand the role of Hedgehog (Hh) signaling in tumor aggressiveness in patients with PTC. Subjects were patients who underwent thyroidectomy from 2012 to 2013 in a single institution. Frozen or paraffin-embedded tumor tissues with contralateral-matched normal thyroid tissues were collected. Hh signaling activity was analyzed by quantitative RT-PCR (qRT-PCR) and immunohistochemical (IHC) staining. Datasets from Gene Expression Omnibus (GEO) (National Center for Biotechnology Information) were subjected to Gene Set Enrichment Analysis (GSEA). BRAFT1799A and telomerase reverse transcriptase promoter mutation C228T were analyzed by direct sequencing. Among 137 patients with PTC, glioma-associated oncogene homolog 1 (GLI1) group III (patients in whom the ratio of GLI1 messenger ribonucleic acid (mRNA) level in tumor tissue to GLI1 mRNA level in matched normal tissue was in the upper third of the subject population) had elevated risk for ETE (odds ratio [OR] 4.381, 95% confidence interval [CI] 1.414–13.569, P = 0.01) and LNM (OR 5.627, 95% CI 1.674–18.913, P = 0.005). Glioma-associated oncogene homolog 2 (GLI2) group III also had elevated risk for ETE (OR 4.152, 95% CI 1.292–13.342, P = 0.017) and LNM (OR 3.924, 95% CI 1.097–14.042, P = 0.036). GSEA suggested that higher GLI1 expression is associated with expression of the KEGG gene set related to axon guidance (P = 0.031, false discovery rate < 0.05), as verified by qRT-PCR and IHC staining in our subjects. GLI1 and GLI2 expressions were clearly related to aggressive clinicopathological features and aberrant activation of GLI1 involved in the axon guidance pathway. These results may contribute to development of new

  5. GLI1 Transcription Factor Affects Tumor Aggressiveness in Patients With Papillary Thyroid Cancers.

    PubMed

    Lee, Jandee; Jeong, Seonhyang; Lee, Cho Rok; Ku, Cheol Ryong; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Shin, Dong Yeob; Chung, Woong Youn; Lee, Eun Jig; Jo, Young Suk

    2015-06-01

    A significant proportion of patients with papillary thyroid cancer (PTC) present with extrathyroidal extension (ETE) and lymph node metastasis (LNM). However, the molecular mechanism of tumor invasiveness in PTC remains to be elucidated. The aim of this study is to understand the role of Hedgehog (Hh) signaling in tumor aggressiveness in patients with PTC. Subjects were patients who underwent thyroidectomy from 2012 to 2013 in a single institution. Frozen or paraffin-embedded tumor tissues with contralateral-matched normal thyroid tissues were collected. Hh signaling activity was analyzed by quantitative RT-PCR (qRT-PCR) and immunohistochemical (IHC) staining. Datasets from Gene Expression Omnibus (GEO) (National Center for Biotechnology Information) were subjected to Gene Set Enrichment Analysis (GSEA). BRAFT1799A and telomerase reverse transcriptase promoter mutation C228T were analyzed by direct sequencing. Among 137 patients with PTC, glioma-associated oncogene homolog 1 (GLI1) group III (patients in whom the ratio of GLI1 messenger ribonucleic acid (mRNA) level in tumor tissue to GLI1 mRNA level in matched normal tissue was in the upper third of the subject population) had elevated risk for ETE (odds ratio [OR] 4.381, 95% confidence interval [CI] 1.414-13.569, P = 0.01) and LNM (OR 5.627, 95% CI 1.674-18.913, P = 0.005). Glioma-associated oncogene homolog 2 (GLI2) group III also had elevated risk for ETE (OR 4.152, 95% CI 1.292-13.342, P = 0.017) and LNM (OR 3.924, 95% CI 1.097-14.042, P = 0.036). GSEA suggested that higher GLI1 expression is associated with expression of the KEGG gene set related to axon guidance (P = 0.031, false discovery rate < 0.05), as verified by qRT-PCR and IHC staining in our subjects.GLI1 and GLI2 expressions were clearly related to aggressive clinicopathological features and aberrant activation of GLI1 involved in the axon guidance pathway. These results may contribute to development of new prognostic markers

  6. AT9283, a novel aurora kinase inhibitor, suppresses tumor growth in aggressive B-cell lymphomas.

    PubMed

    Qi, Wenqing; Liu, Xiaobing; Cooke, Laurence S; Persky, Daniel O; Miller, Thomas P; Squires, Matthew; Mahadevan, Daruka

    2012-06-15

    Aurora kinases are oncogenic serine/threonine kinases that play key roles in regulating the mitotic phase of the eukaryotic cell cycle. Auroras are overexpressed in numerous tumors including B-cell non-Hodgkin's lymphomas and are validated oncology targets. AT9283, a pan-aurora inhibitor inhibited growth and survival of multiple solid tumors in vitro and in vivo. In this study, we demonstrated that AT9283 had potent activity against Aurora B in a variety of aggressive B-(non-Hodgkin lymphoma) B-NHL cell lines. Cells treated with AT9283 exhibited endoreduplication confirming the mechanism of action of an Aurora B inhibitor. Also, treatment of B-NHL cell lines with AT9283 induced apoptosis in a dose and time dependent manner and inhibited cell proliferation with an IC(50) < 1 μM. It is well known that inhibition of auroras (A or B) synergistically enhances the effects of microtubule targeting agents such as taxanes and vinca alkaloids to induce antiproliferation and apoptosis. We evaluated whether AT9283 in combination with docetaxel is more efficient in inducing apoptosis than AT9283 or docetaxel alone. At very low doses (5 nM) apoptosis was doubled in the combination (23%) compared to AT9283 or docetaxel alone (10%). A mouse xenograft model of mantle cell lymphoma demonstrated that AT9283 at 15 mg/kg and docetaxel (10 mg/kg) alone had modest anti-tumor activity. However, AT9283 at 20 mg/kg and AT9283 (15 or 20 mg/kg) plus docetaxel (10 mg/kg) demonstrated a statistically significant tumor growth inhibition and enhanced survival. Together, our results suggest that AT9283 plus docetaxel may represent a novel therapeutic strategy in B-cell NHL and warrant early phase clinical trial evaluation. PMID:21796626

  7. AT9283, a novel aurora kinase inhibitor, suppresses tumor growth in aggressive B-cell lymphomas.

    PubMed

    Qi, Wenqing; Liu, Xiaobing; Cooke, Laurence S; Persky, Daniel O; Miller, Thomas P; Squires, Matthew; Mahadevan, Daruka

    2012-06-15

    Aurora kinases are oncogenic serine/threonine kinases that play key roles in regulating the mitotic phase of the eukaryotic cell cycle. Auroras are overexpressed in numerous tumors including B-cell non-Hodgkin's lymphomas and are validated oncology targets. AT9283, a pan-aurora inhibitor inhibited growth and survival of multiple solid tumors in vitro and in vivo. In this study, we demonstrated that AT9283 had potent activity against Aurora B in a variety of aggressive B-(non-Hodgkin lymphoma) B-NHL cell lines. Cells treated with AT9283 exhibited endoreduplication confirming the mechanism of action of an Aurora B inhibitor. Also, treatment of B-NHL cell lines with AT9283 induced apoptosis in a dose and time dependent manner and inhibited cell proliferation with an IC(50) < 1 μM. It is well known that inhibition of auroras (A or B) synergistically enhances the effects of microtubule targeting agents such as taxanes and vinca alkaloids to induce antiproliferation and apoptosis. We evaluated whether AT9283 in combination with docetaxel is more efficient in inducing apoptosis than AT9283 or docetaxel alone. At very low doses (5 nM) apoptosis was doubled in the combination (23%) compared to AT9283 or docetaxel alone (10%). A mouse xenograft model of mantle cell lymphoma demonstrated that AT9283 at 15 mg/kg and docetaxel (10 mg/kg) alone had modest anti-tumor activity. However, AT9283 at 20 mg/kg and AT9283 (15 or 20 mg/kg) plus docetaxel (10 mg/kg) demonstrated a statistically significant tumor growth inhibition and enhanced survival. Together, our results suggest that AT9283 plus docetaxel may represent a novel therapeutic strategy in B-cell NHL and warrant early phase clinical trial evaluation.

  8. The interdisciplinary approach of an aggressive giant cell tumor of bone complicated with a fracture of the distal femur.

    PubMed

    Vîlcioiu, Iulian Daniel; Zamfirescu, Dragoş George; Cristescu, Ioan; Ursache, Andrei; Popescu, Şerban Arghir; Creangă, Cosmin Antoniu; Lascăr, Ioan

    2016-01-01

    Giant cell tumor of bone (GCTB) represents one of the commonest bone tumors encountered by an orthopedic surgeon. The giant-cell tumor is generally classified as benign but the fast growing rhythm and the aggressive soft-tissue invasion may in some cases demonstrate a malign potential of the tumor. We present the case of an aggressive giant cell tumor in a young patient that was first diagnosed in our emergency department with a fracture of the distal femur after a low energy trauma. With further examinations, we discovered that the tumor was invading the both femoral condyles and was vascularized by three major arterial pedicles. The onset of his problems was the femoral fracture and the changes on the major vessels, muscles and nerves. After an interdisciplinary approach of the patient and a meticulous preoperative planning, we decided to make an extensive total resection of the tumor followed by a complex reconstruction surgery for the bone. A very stable fixation of a vascularized graft allowed the bone to heal even if the surrounded soft-tissue was almost completely invaded by the tumor and removed during the excision. The follow-up of this case demonstrated that using an interdisciplinary approach of the patient with the Plastic Surgery team, we manage to remove the tumor within oncological limits and achieved bone healing with good stability of the distal femur. PMID:27516036

  9. Warburg Effect’s Manifestation in Aggressive Pheochromocytomas and Paragangliomas: Insights from a Mouse Cell Model Applied to Human Tumor Tissue

    PubMed Central

    Fliedner, Stephanie M. J.; Kaludercic, Nina; Jiang, Xiao-Sheng; Hansikova, Hana; Hajkova, Zuzana; Sladkova, Jana; Limpuangthip, Andrea; Backlund, Peter S.; Wesley, Robert; Martiniova, Lucia; Jochmanova, Ivana; Lendvai, Nikoletta K.; Breza, Jan; Yergey, Alfred L.; Paolocci, Nazareno; Tischler, Arthur S.; Zeman, Jiri; Porter, Forbes D.; Lehnert, Hendrik; Pacak, Karel

    2012-01-01

    A glycolytic profile unifies a group of pheochromocytomas and paragangliomas (PHEOs/PGLs) with distinct underlying gene defects, including von Hippel-Lindau (VHL) and succinate dehydrogenase B (SDHB) mutations. Nevertheless, their tumor aggressiveness is distinct: PHEOs/PGLs metastasize rarely in VHL-, but frequently in SDHB-patients. To date, the molecular mechanisms causing the more aggressive phenotype in SDHB-PHEOs/PGLs remain largely unknown. Recently, however, an excellent model to study aggressive PHEOs (mouse tumor tissue (MTT) cells) has been developed from mouse PHEO cells (MPC). We employed this model for a proteomics based approach to identify changes characteristic for tumor aggressiveness, which we then explored in a homogeneous set of human SDHB- and VHL-PHEOs/PGLs. The increase of glucose transporter 1 in VHL, and of hexokinase 2 in VHL and SDHB, confirmed their glycolytic profile. In agreement with the cell model and in support of decoupling of glycolysis, the Krebs cycle and oxidative phosphorylation (OXPHOS), SDHB tumors showed increased lactate dehydrogenase levels. In SDHB-PGLs OXPHOS complex activity was increased at complex III and, as expected, decreased at complex II. Moreover, protein and mRNA expression of all tested OXPHOS-related genes were higher in SDHB- than in VHL-derived tumors. Although there was no direct evidence for increased reactive oxygen species production, elevated superoxide dismutase 2 expression may reflect elevated oxidative stress in SDHB-derived PHEOs/PGLs. For the first time, we show that despite dysfunction in complex II and evidence for a glycolytic phenotype, the Warburg effect does not seem to fully apply to SDHB-PHEOs/PGLs with respect to decreased OXPHOS. In addition, we present evidence for increased LDHA and SOD2 expression in SDHB-PHEOs/PGLs, proteins that have been proposed as promising therapeutic targets in other cancers. This study provides new insight into pathogenic mechanisms in aggressive human

  10. An unusually large aggressive adenomatoid odontogenic tumor of maxilla involving the third molar: A clinical case report

    PubMed Central

    Dhupar, Vikas; Akkara, Francis; Khandelwal, Pulkit

    2016-01-01

    Adenomatoid odontogenic tumor (AOT) is a rare tumor comprising only 3% of all odontogenic tumors. It is a benign, encapsulated, noninvasive, nonaggressive, slowly growing odontogenic lesion associated with an impacted tooth. These lesions may go unnoticed for years. The usual treatment is enucleation and curettage, and the lesion does not recur. Here, we present a rare case of an unusually large aggressive AOT of maxilla associated with impacted third molar. The authors also discuss clinical, radiographic, histopathologic, and therapeutic features of the case. Subtotal maxillectomy with simultaneous reconstruction of the surgical defect with temporalis myofascial flap was planned and carried out. PMID:27095910

  11. Computer-Aided Image Analysis and Fractal Synthesis in the Quantitative Evaluation of Tumor Aggressiveness in Prostate Carcinomas

    PubMed Central

    Waliszewski, Przemyslaw

    2016-01-01

    The subjective evaluation of tumor aggressiveness is a cornerstone of the contemporary tumor pathology. A large intra- and interobserver variability is a known limiting factor of this approach. This fundamental weakness influences the statistical deterministic models of progression risk assessment. It is unlikely that the recent modification of tumor grading according to Gleason criteria for prostate carcinoma will cause a qualitative change and improve significantly the accuracy. The Gleason system does not allow the identification of low aggressive carcinomas by some precise criteria. The ontological dichotomy implies the application of an objective, quantitative approach for the evaluation of tumor aggressiveness as an alternative. That novel approach must be developed and validated in a manner that is independent of the results of any subjective evaluation. For example, computer-aided image analysis can provide information about geometry of the spatial distribution of cancer cell nuclei. A series of the interrelated complexity measures characterizes unequivocally the complex tumor images. Using those measures, carcinomas can be classified into the classes of equivalence and compared with each other. Furthermore, those measures define the quantitative criteria for the identification of low- and high-aggressive prostate carcinomas, the information that the subjective approach is not able to provide. The co-application of those complexity measures in cluster analysis leads to the conclusion that either the subjective or objective classification of tumor aggressiveness for prostate carcinomas should comprise maximal three grades (or classes). Finally, this set of the global fractal dimensions enables a look into dynamics of the underlying cellular system of interacting cells and the reconstruction of the temporal-spatial attractor based on the Taken’s embedding theorem. Both computer-aided image analysis and the subsequent fractal synthesis could be performed

  12. Computer-Aided Image Analysis and Fractal Synthesis in the Quantitative Evaluation of Tumor Aggressiveness in Prostate Carcinomas.

    PubMed

    Waliszewski, Przemyslaw

    2016-01-01

    The subjective evaluation of tumor aggressiveness is a cornerstone of the contemporary tumor pathology. A large intra- and interobserver variability is a known limiting factor of this approach. This fundamental weakness influences the statistical deterministic models of progression risk assessment. It is unlikely that the recent modification of tumor grading according to Gleason criteria for prostate carcinoma will cause a qualitative change and improve significantly the accuracy. The Gleason system does not allow the identification of low aggressive carcinomas by some precise criteria. The ontological dichotomy implies the application of an objective, quantitative approach for the evaluation of tumor aggressiveness as an alternative. That novel approach must be developed and validated in a manner that is independent of the results of any subjective evaluation. For example, computer-aided image analysis can provide information about geometry of the spatial distribution of cancer cell nuclei. A series of the interrelated complexity measures characterizes unequivocally the complex tumor images. Using those measures, carcinomas can be classified into the classes of equivalence and compared with each other. Furthermore, those measures define the quantitative criteria for the identification of low- and high-aggressive prostate carcinomas, the information that the subjective approach is not able to provide. The co-application of those complexity measures in cluster analysis leads to the conclusion that either the subjective or objective classification of tumor aggressiveness for prostate carcinomas should comprise maximal three grades (or classes). Finally, this set of the global fractal dimensions enables a look into dynamics of the underlying cellular system of interacting cells and the reconstruction of the temporal-spatial attractor based on the Taken's embedding theorem. Both computer-aided image analysis and the subsequent fractal synthesis could be performed

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

    PubMed Central

    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

  14. Gastric-type Endocervical Adenocarcinoma: An Aggressive Tumor With Unusual Metastatic Patterns and Poor Prognosis.

    PubMed

    Karamurzin, Yevgeniy S; Kiyokawa, Takako; Parkash, Vinita; Jotwani, Anjali R; Patel, Prusha; Pike, Malcolm C; Soslow, Robert A; Park, Kay J

    2015-11-01

    Gastric-type adenocarcinoma of the uterine cervix (GAS) is a rare variant of mucinous endocervical adenocarcinoma not etiologically associated with human papillomavirus (HPV) infection, with minimal deviation adenocarcinoma (MDA) at the well-differentiated end of the morphologic spectrum. These tumors are reported to have worse prognosis than usual HPV associated endocervical adenocarcinoma (UEA). A retrospective review of GAS was performed from the pathology databases of 3 institutions spanning 20 years. Stage, metastatic patterns, and overall survival were documented. Forty GAS cases were identified, with clinical follow-up data available for 38. The tumors were subclassified as MDA (n=13) and non-MDA GAS (n=27). Two patients were syndromic (1 Li-Fraumeni, 1 Peutz-Jeghers). At presentation, 59% were advanced stage (FIGO II to IV), 50% had lymph node metastases, 35% had ovarian involvement, 20% had abdominal disease, 39% had at least 1 site of metastasis at the time of initial surgery, and 12% of patients experienced distant recurrence. The metastatic sites included lymph nodes, adnexa, omentum, bowel, peritoneum, diaphragm, abdominal wall, bladder, vagina, appendix, and brain. Follow-up ranged from 1.4 to 136.0 months (mean, 33.9 mo); 20/38 (52.6%) had no evidence of disease, 3/38 (7.9%) were alive with disease, and 15/38 (39.5%) died of disease. Disease-specific survival at 5 years was 42% for GAS versus 91% for UEA. There were no survival differences between MDA and non-MDA GAS. GAS represents a distinct, biologically aggressive type of endocervical adenocarcinoma. The majority of patients present at advanced stage and pelvic, abdominal, and distant metastases are not uncommon.

  15. Aberrant RSPO3-LGR4 signaling in Keap1-deficient lung adenocarcinomas promotes tumor aggressiveness.

    PubMed

    Gong, X; Yi, J; Carmon, K S; Crumbley, C A; Xiong, W; Thomas, A; Fan, X; Guo, S; An, Z; Chang, J T; Liu, Q J

    2015-09-01

    The four R-spondins (RSPO1-4) and their three related receptors LGR4, 5 and 6 (LGR4-6) have emerged as a major ligand-receptor system with critical roles in development and stem cell survival through modulation of Wnt signaling. Recurrent, gain-of-expression gene fusions of RSPO2 (to EIF3E) and RSPO3 (to PTPRK) occur in a subset of human colorectal cancer. However, the exact roles and mechanisms of the RSPO-LGR system in oncogenesis remain largely unknown. We found that RSPO3 is aberrantly expressed at high levels in approximately half of Keap1-mutated lung adenocarcinomas (ADs). This high RSPO3 expression is driven by a combination of demethylation of its own promoter region and deficiency in Keap1 instead of gene fusion as in colon cancer. Patients with RSPO3-high tumors (~9%, 36/412) displayed much poorer survival than the rest of the cohort (median survival of 28 vs 163 months, log-rank test P<0.0001). Knockdown (KD) of RSPO3, LGR4 or their signaling mediator IQGAP1 in lung cancer cell lines with Keap1 deficiency and high RSPO3-LGR4 expression led to reduction in cell proliferation and migration in vitro, and KD of LGR4 or IQGAP1 resulted in decrease in tumor growth and metastasis in vivo. These findings suggest that aberrant RSPO3-LGR4 signaling potentially acts as a driving mechanism in the aggressiveness of Keap1-deficient lung ADs.

  16. Aberrant RSPO3-LGR4 signaling in Keap1-deficient lung adenocarcinomas promotes tumor aggressiveness

    PubMed Central

    Gong, Xing; Yi, Jing; Carmon, Kendra S.; Crumbley, Christine A.; Xiong, Wei; Thomas, Anthony; Fan, Xuejun; Guo, Shan; An, Zhiqiang; Chang, Jeffrey T.; Liu, Qingyun J.

    2015-01-01

    The four R-spondins (RSPO1-4) and their three related receptors LGR4, 5 and 6 (LGR4-6) have emerged as a major ligand-receptor system with critical roles in development and stem cell survival through modulation of Wnt signaling. Recurrent, gain-of-expression gene fusions of RSPO2 (to EIF3E) and RSPO3 (to PTPRK) occur in a subset of human colorectal cancer. However, the exact roles and mechanisms of the RSPO-LGR system in oncogenesis remain largely unknown. We found that RSPO3 is aberrantly expressed at high levels in approximately half of the Keap1-mutated lung adenocarcinomas. This high RSPO3 expression is driven by a combination of demethylation of its own promoter region and deficiency in Keap1 instead of gene fusion as in colon cancer. Patients with RSPO3-high tumors (~9%, 36/412) displayed much poorer survival than the rest of the cohorts (median survival of 28 vs. 163 months, logrank test p < 0.0001). Knockdown of RSPO3, LGR4, or their signaling mediator IQGAP1 in lung cancer cell lines with Keap1 deficiency and high RSPO3-LGR4 expression led to reduction in cell proliferation and migration in vitro, and knockdown of LGR4 or IQGAP1 resulted in decrease in tumor growth and metastasis in vivo. These findings suggest that aberrant RSPO3-LGR4 signaling potentially acts as a driving mechanism in the aggressiveness of Keap1-deficient lung adenocarcinomas. PMID:25531322

  17. Highly Aggressive HPV-related Oropharyngeal Cancer: Clinical, Radiologic, and Pathologic Characteristics

    PubMed Central

    Kaka, Azeem S.; Kumar, Bhavna; Kumar, Pawan; Wakely, Paul E.; Kirsch, Claudia M.; Old, Matthew O.; Ozer, Enver; Agrawal, Amit; Carrau, Ricardo E.; Schuller, David E.; Siddiqui, Farzan; Teknos, Theodoros N.

    2013-01-01

    Objectives While the majority of HPV+ oropharyngeal squamous cell carcinomas have a favorable prognosis, we search for markers of poor prognosis by carefully examining a subset of highly-aggressive cases. Study Design Seven patients with HPV+ oropharyngeal cancer who presented with non-pulmonary distant metastasis or developed distant metastasis post-treatment were identified. Eight control cases were chosen which responded well to treatment. Pathology and radiological studies were reviewed and compared. Results Two cases displayed a small cell carcinoma (SmCC) component upon pathologic review. Biomarker analysis revealed lower expression of NOTCH1 in the aggressive cohort in comparison to controls (p=0.04). Cases showed a predominance of clustering of lymph nodes, extracapsular spread and central tumor necrosis. Conclusion While most HPV-related oropharyngeal cancers display a positive prognosis, it is evident that there is a subset, which behave more aggressively. This early investigation identifies pathologic and radiologic features that may help to predict this behavior. PMID:23770280

  18. Incidence, Types and Characteristics of Aggressive Behaviour in Treatment Facilities for Adults with Mild Intellectual Disability and Severe Challenging Behaviour

    ERIC Educational Resources Information Center

    Tenneij, N. H.; Koot, H. M.

    2008-01-01

    Background: Inpatient aggression in treatment facilities for persons with intellectual disability (ID) can have aversive consequences, for co-clients and staff, but also for the aggressors themselves. To manage and eventually prevent inpatient aggressive incidents, more knowledge about their types and characteristics is necessary. Method: In four…

  19. Sub-100 nm Gold Nanomatryoshkas Improve Photo-thermal Therapy Efficacy in Large and Highly Aggressive Triple Negative Breast Tumors

    PubMed Central

    Bishnoi, Sandra; Urban, Alexander; Charron, Heather; Mitchell, Tamika; Shea, Martin; Nanda, Sarmistha; Schiff, Rachel; Halas, Naomi; Joshi, Amit

    2014-01-01

    There is an unmet need for efficient near-infrared photothermal transducers for the treatment of highly aggressive cancers and large tumors where the penetration of light can be substantially reduced, and the intra-tumoral nanoparticle transport is restricted due to the presence of hypoxic or nectrotic regions. We report the performance advantages obtained by sub 100 nm gold nanomatryushkas, comprising of concentric gold-silica-gold layers compared to conventional ~150 nm silica core gold nanoshells for photothermal therapy of triple negative breast cancer. We demonstrate that a 33% reduction in silica-core-gold-shell nanoparticle size, while retaining near-infrared plasmon resonance, and keeping the nanoparticle surface charge constant, results in a four to five fold tumor accumulation of nanoparticles following equal dose of injected gold for both sizes. The survival time of mice bearing large (>1000 mm3) and highly aggressive triple negative breast tumors is doubled for the nanomatryushka treatment group under identical photo-thermal therapy conditions. The higher absorption cross-section of a nanomatryoshka results in a higher efficiency of photonic to thermal energy conversion and coupled with 4-5X accumulation within large tumors results in superior therapy efficacy. PMID:25051221

  20. Epidermal growth factor receptor as a novel molecular target for aggressive papillary tumors in the middle ear and temporal bone

    PubMed Central

    Kawabata, Shigeru; Christine Hollander, M; Munasinghe, Jeeva P.; Brinster, Lauren R.; Mercado-Matos, José R.; Li, Jie; Regales, Lucia; Pao, William; Jänne, Pasi A.; Wong, Kwok-Kin; Butman, John A.; Lonser, Russell R.; Hansen, Marlan R.; Gurgel, Richard K.; Vortmeyer, Alexander O.; Dennis, Phillip A.

    2015-01-01

    Adenomatous tumors in the middle ear and temporal bone are rare but highly morbid because they are difficult to detect prior to the development of audiovestibular dysfunction. Complete resection is often disfiguring and difficult because of location and the late stage at diagnosis, so identification of molecular targets and effective therapies is needed. Here, we describe a new mouse model of aggressive papillary ear tumor that was serendipitously discovered during the generation of a mouse model for mutant EGFR-driven lung cancer. Although these mice did not develop lung tumors, 43% developed head tilt and circling behavior. Magnetic resonance imaging (MRI) scans showed bilateral ear tumors located in the tympanic cavity. These tumors expressed mutant EGFR as well as active downstream targets such as Akt, mTOR and ERK1/2. EGFR-directed therapies were highly effective in eradicating the tumors and correcting the vestibular defects, suggesting these tumors are addicted to EGFR. EGFR activation was also observed in human ear neoplasms, which provides clinical relevance for this mouse model and rationale to test EGFR-targeted therapies in these rare neoplasms. PMID:26027747

  1. [Prevalence and clinicopathological characteristics of giant cell tumors].

    PubMed

    Estrada-Villaseñor, E G; Linares-González, L M; Delgado-Cedillo, E A; González-Guzmán, R; Rico-Martínez, G

    2015-01-01

    The frequency of giant cell tumors reported in the literature is very variable. Considering that our population has its own features, which distinguish it from the Anglo-Saxon and Asian populations, we think that both the frequency and the clinical characteristics of giant cell tumors in our population are different. The major aim of this paper was to determine the frequency and clinicopathological characteristics of giant cell tumors of the bone. A cross-sectional descriptive study was conducted of the cases diagnosed at our service as giant cell tumors of the bone from January to December 2013. The electronic clinical records, radiologic records and histologic slides from each case were reviewed. Giant cell tumors represented 17% of total bone tumors and 28% of benign tumors. Patients included 13 females and 18 males. The most frequent locations of giant cell tumors were: the proximal tibia, 9 cases (29%), and the distal femur, 6 cases (19%). Forty-five percent of giant cell tumors were associated with aneurysmal bone cyst (ABC) (14 cases) and one case (3%) was malignant. The frequency of giant cell tumors in this case series was intermediate, that is, higher than the one reported in Anglo-Saxon countries (usually low), but without reaching the frequency rates reported in Asian countries (high).

  2. [Prevalence and clinicopathological characteristics of giant cell tumors].

    PubMed

    Estrada-Villaseñor, E G; Linares-González, L M; Delgado-Cedillo, E A; González-Guzmán, R; Rico-Martínez, G

    2015-01-01

    The frequency of giant cell tumors reported in the literature is very variable. Considering that our population has its own features, which distinguish it from the Anglo-Saxon and Asian populations, we think that both the frequency and the clinical characteristics of giant cell tumors in our population are different. The major aim of this paper was to determine the frequency and clinicopathological characteristics of giant cell tumors of the bone. A cross-sectional descriptive study was conducted of the cases diagnosed at our service as giant cell tumors of the bone from January to December 2013. The electronic clinical records, radiologic records and histologic slides from each case were reviewed. Giant cell tumors represented 17% of total bone tumors and 28% of benign tumors. Patients included 13 females and 18 males. The most frequent locations of giant cell tumors were: the proximal tibia, 9 cases (29%), and the distal femur, 6 cases (19%). Forty-five percent of giant cell tumors were associated with aneurysmal bone cyst (ABC) (14 cases) and one case (3%) was malignant. The frequency of giant cell tumors in this case series was intermediate, that is, higher than the one reported in Anglo-Saxon countries (usually low), but without reaching the frequency rates reported in Asian countries (high). PMID:27403516

  3. Presence of sst5TMD4, a truncated splice variant of the somatostatin receptor subtype 5, is associated to features of increased aggressiveness in pancreatic neuroendocrine tumors

    PubMed Central

    Gahete, Manuel D.; Serrano-Somavilla, Ana; Villa-Osaba, Alicia; Adrados, Magdalena; Ibáñez-Costa, Alejandro; Martín-Pérez, Elena; Culler, Michael D.

    2016-01-01

    Purpose Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and heterogeneous tumors, and their biological behavior is not well known. We studied the presence and potential functional roles of somatostatin receptors (sst1-5), focusing particularly on the truncated variants (sst5TMD4, sst5TMD5) and on their relationships with the angiogenic system (Ang/Tie-2 and VEGF) in human GEP-NETs. Experimental Design We evaluated 42 tumor tissue samples (26 primary/16 metastatic) from 26 patients with GEP-NETs, and 30 non-tumoral tissues (26 from adjacent non-tumor regions and 4 from normal controls) from a single center. Expression of sst1-5, sst5TMD4, sst5TMD5, Ang1-2, Tie-2 and VEGF was analyzed using real-time qPCR, immunofluorescence and immunohistochemistry. Expression levels were associated with tumor characteristics and clinical outcomes. Functional role of sst5TMD4 was analyzed in GEP-NET cell lines. Results sst1 exhibited the highest expression in GEP-NET, whilst sst2 was the most frequently observed sst-subtype (90.2%). Expression levels of sst1, sst2, sst3, sst5TMD4, and sst5TMD5 were significantly higher in tumor tissues compared to their adjacent non-tumoral tissue. Lymph-node metastases expressed higher levels of sst5TMD4 than in its corresponding primary tumor tissue. sst5TMD4 was also significantly higher in intestinal tumor tissues from patients with residual disease of intestinal origin compared to those with non-residual disease. Functional assays demonstrated that the presence of sst5TMD4 was associated to enhanced malignant features in GEP-NET cells. Angiogenic markers correlated positively with sst5TMD4, which was confirmed by immunohistochemical/fluorescence studies. Conclusions sst5TMD4 is overexpressed in GEP-NETs and is associated to enhanced aggressiveness, suggesting its potential value as biomarker and target in GEP-NETs. PMID:26673010

  4. Effects of structural and dynamic family characteristics on the development of depressive and aggressive problems during adolescence. The TRAILS study.

    PubMed

    Sijtsema, J J; Oldehinkel, A J; Veenstra, R; Verhulst, F C; Ormel, J

    2014-06-01

    Both structural (i.e., SES, familial psychopathology, family composition) and dynamic (i.e., parental warmth and rejection) family characteristics have been associated with aggressive and depressive problem development. However, it is unclear to what extent (changes in) dynamic family characteristics have an independent effect on problem development while accounting for stable family characteristics and comorbid problem development. This issue was addressed by studying problem development in a large community sample (N = 2,230; age 10-20) of adolescents using Linear Mixed models. Paternal and maternal warmth and rejection were assessed via the Egna Minnen Beträffande Uppfostran for Children (EMBU-C). Aggressive and depressive problems were assessed via subscales of the Youth/Adult Self-Report. Results showed that dynamic family characteristics independently affected the development of aggressive problems. Moreover, maternal rejection in preadolescence and increases in paternal rejection were associated with aggressive problems, whereas decreases in maternal rejection were associated with decreases in depressive problems over time. Paternal and maternal warmth in preadolescence was associated with fewer depressive problems during adolescence. Moreover, increases in paternal warmth were associated with fewer depressive problems over time. Aggressive problems were a stable predictor of depressive problems over time. Finally, those who increased in depressive problems became more aggressive during adolescence, whereas those who decreased in depressive problems became also less aggressive. Besides the effect of comorbid problems, problem development is to a large extent due to dynamic family characteristics, and in particular to changes in parental rejection, which leaves much room for parenting-based interventions. PMID:24043499

  5. Colorectal cancer-derived tumor spheroids retain the characteristics of original tumors.

    PubMed

    Lee, Sun-Hwa; Hong, Jun Hwa; Park, Hwan Ki; Park, Jun Seok; Kim, Bo-Kyung; Lee, Jung-Yi; Jeong, Ji Yun; Yoon, Ghil Suk; Inoue, Masahiro; Choi, Gyu-Seog; Lee, In-Kyu

    2015-10-10

    Primary cultures of cancer cells are useful for developing personalized medicine. In this study, we characterized three lines of three-dimensional (3D) tumor spheroids established directly from tumor tissues of patients with colorectal cancers (CRCs). Each line mainly included EpCAM-positive cells and cells expressing putative cancer stem cell markers such as CD133, CD44, CD24, ALDH1, and LGR5. These characteristic stem cell markers remained identically for months in vitro. Short tandem repeat genotyping suggested that genetic fingerprints of these tumor spheroids were similar to those of the original tumor tissues from which they were derived. Mutational analysis showed that each line had the same mutation profile for APC, KRAS, MLH1, serine-threonine kinase 11, and TP53 as its parental tumor tissue. One line harboring an activating KRAS mutation was resistant to cetuximab while the remaining two lines harboring wild-type KRAS showed different responses to cetuximab. Immunohistochemical analysis showed that xenograft tumors derived from these lines retained the histopathological and mutational patterns of their parental tumors. Collectively, these results clearly showed that 3D tumor spheroids directly generated from tumor tissues of patients with CRCs preserved the characteristics of their parental tumor tissues and could be used for developing personalized medicines for CRCs.

  6. Nuclear maspin expression correlates with the CpG island methylator phenotype and tumor aggressiveness in colorectal cancer.

    PubMed

    Kim, Jung Ho; Cho, Nam-Yun; Bae, Jeong Mo; Kim, Kyung-Ju; Rhee, Ye-Young; Lee, Hye Seung; Kang, Gyeong Hoon

    2015-01-01

    It has been suggested that nuclear expression of maspin (mammary serine protease inhibitor; also known as SERPINB5) in colorectal cancer (CRC) is associated with proximal colonic tumor location, mucinous and poorly differentiated histology, microsatellite instability-high (MSI-H), and poor prognosis. Based on these findings, there may be a potential association between nuclear maspin expression and the CpG island methylator phenotype (CIMP) in CRC, but no study has elucidated this issue. Here, we evaluated maspin protein expression status by immunohistochemistry in 216 MSI-H CRCs. CIMP status was also determined by methylation-specific quantitative PCR method (MethyLight) using eight CIMP markers (MLH1, NEUROG1, CRABP1, CACNA1G, CDKN2A (p16), IGF2, SOCS1, and RUNX3) in 216 MSI-H CRCs. Associations between maspin expression status and various pathological, molecular, and survival data were statistically analyzed. Among the 216 MSI-H CRCs, 111 (51%) cases presented nuclear maspin-positive tumors. Nuclear maspin-positive MSI-H CRCs were significantly associated with proximal tumor location (P = 0.003), tumor budding (P < 0.001), lymphovascular invasion (P = 0.001), perineural invasion (P = 0.008), absence of peritumoral lymphoid reaction (P = 0.045), lymph node metastasis (P = 0.003), distant metastasis (P = 0.005), advanced AJCC/UICC stage (stage III/IV) (P = 0.001), and CIMP-high (CIMP-H) status (P < 0.001). Patients with nuclear maspin-positive tumors showed worse disease-free survival than patients with nuclear maspin-negative tumors (log-rank P = 0.025). In conclusion, nuclear maspin expression is molecularly associated with CIMP-H rather than MSI-H, and clinicopathologically correlates with tumor aggressiveness in CRC.

  7. Breast cancer among the oldest old: tumor characteristics, treatment choices, and survival.

    PubMed

    Schonberg, Mara A; Marcantonio, Edward R; Li, Donglin; Silliman, Rebecca A; Ngo, Long; McCarthy, Ellen P

    2010-04-20

    PURPOSE Few data are available on breast cancer characteristics, treatment, and survival for women age 80 years or older. PATIENTS AND METHODS We used the linked Surveillance, Epidemiology and End Results-Medicare data set from 1992 to 2003 to examine tumor characteristics, treatments (mastectomy, breast-conserving surgery [BCS] with radiation therapy or alone, or no surgery), and outcomes of women age 80 years or older (80 to 84, 85 to 89, > or = 90 years) with stage I/II breast cancer compared with younger women (age 67 to 79 years). We used Cox proportional hazard models to examine the impact of age on breast cancer-related and other causes of death. Analyses were performed within stage, adjusted for tumor and sociodemographic characteristics, treatments received, and comorbidities. Results In total, 49,616 women age 67 years or older with stage I/II disease were included. Tumor characteristics (grade, hormone receptivity) were similar across age groups. Treatment with BCS alone increased with age, especially after age 80. The risk of dying from breast cancer increased with age, significantly after age 80. For stage I disease, the adjusted hazard ratio of dying from breast cancer for women age > or = 90 years compared with women age 67 to 69 years was 2.6 (range, 2.0 to 3.4). Types of treatments received were significantly associated with age and comorbidity, with age as the stronger predictor (26% of women age > or = 80 years without comorbidity received BCS alone or no surgery compared with 6% of women age 67 to 79 years). CONCLUSION Women age > or = 80 years have breast cancer characteristics similar to those of younger women yet receive less aggressive treatment and experience higher mortality from early-stage breast cancer. Future studies should focus on identifying tumor and patient characteristics to help target treatments to the oldest women most likely to benefit.

  8. Altered PTEN, ATRX, CHGA, CHGB, and TP53 expression are associated with aggressive VHL-associated pancreatic neuroendocrine tumors.

    PubMed

    Weisbrod, Allison B; Zhang, Lisa; Jain, Meenu; Barak, Stephanie; Quezado, Martha M; Kebebew, Electron

    2013-06-01

    Von Hippel-Lindau (VHL) syndrome is an inherited cancer syndrome in which 8-17 % of germline mutation carriers develop pancreatic neuroendocrine tumors (PNETs). There is limited data on prognostic markers for PNETs other than Ki-67, which is included in the World Health Organization classification system. Recently, specific genes and pathways have been identified by whole exome sequencing which may be involved in the tumorigenesis of PNETs and may be markers of disease aggressiveness. The objective of this study was to identify molecular markers of aggressive disease in VHL-associated PNETs. The protein expression of eight genes (PTEN, CHGA, CHGB, ATRX, DAXX, CC-3, VEGF, and TP53) was analyzed in PNETs by immunohistochemistry and compared to clinical data, VHL genotype, functional imaging results, and pathologic findings. Subcellular distribution of phosphatase and tensin (PTEN), chromogranin A (CHGA), and alpha thalassemia/mental retardation syndrome X-linked (ATRX) were significantly different by WHO classifications (p ≤ 0.05). There was decreased PTEN nuclear to cytoplasmic ratio (p < 0.01) and decreased CHGA nuclear expression (p = 0.03) in malignant samples as compared to benign. Lower cytoplasmic chromogranin B (CHGB) expression (p = 0.03) was associated with malignant tumors and metastasis. Higher nuclear expression of PTEN was associated with VHL mutations in exon 3 (p = 0.04). Higher PTEN and CHGB expression was associated with higher FDG-PET avidity (p < 0.05). Cytoplasmic expression of CC-3 was associated with higher serum chromogranin A levels (ρ = 0.72, p = 0.02). Lastly, greater cytoplasmic expression of p53 was associated with metastasis. Our findings suggest that altered PTEN, ATRX, CHGA, and CHGB expression are associated with aggressive PNET phenotype in VHL and may serve as useful adjunct prognostic markers to Ki-67 in PNETs.

  9. The biological kinship of hypoxia with CSC and EMT and their relationship with deregulated expression of miRNAs and tumor aggressiveness

    PubMed Central

    Bao, Bin; Azmi, Asfar S.; Ali, Shadan; Ahmad, Aamir; Li, Yiwei; Banerjee, Sanjeev; Kong, Dejuan; Sarkar, Fazlul H.

    2013-01-01

    Hypoxia is one of the fundamental biological phenomena that are intricately associated with the development and aggressiveness of a variety of solid tumors. Hypoxia-inducible factors (HIF) function as a master transcription factor, which regulates hypoxia responsive genes and has been recognized to play critical roles in tumor invasion, metastasis, and chemo-radiation resistance, and contributes to increased cell proliferation, survival, angiogenesis and metastasis. Therefore, tumor hypoxia with deregulated expression of HIF and its biological consequence lead to poor prognosis of patients diagnosed with solid tumors, resulting in higher mortality, suggesting that understanding of the molecular relationship of hypoxia with other cellular features of tumor aggressiveness would be invaluable for developing newer targeted therapy for solid tumors. It has been well recognized that cancer stem cells (CSCs) and epithelial-to-mesenchymal transition (EMT) phenotypic cells are associated with therapeutic resistance and contribute to aggressive tumor growth, invasion, metastasis and believed to be the cause of tumor recurrence. Interestingly, hypoxia and HIF signaling pathway are known to play an important role in the regulation and sustenance of CSCs and EMT phenotype. However, the molecular relationship between HIF signaling pathway with the biology of CSCs and EMT remains unclear although NF-κB, PI3K/Akt/mTOR, Notch, Wnt/β-catenin, and Hedgehog signaling pathways have been recognized as important regulators of CSCs and EMT. In this article, we will discuss the state of our knowledge on the role of HIF-hypoxia signaling pathway and its kinship with CSCs and EMT within the tumor microenvironment. We will also discuss the potential role of hypoxia-induced microRNAs (miRNAs) in tumor development and aggressiveness, and finally discuss the potential effects of nutraceuticals on the biology of CSCs and EMT in the context of tumor hypoxia. PMID:22579961

  10. Dermatofibrosarcoma protuberans, a rare but locally aggressive tumor on finger: clinical and aeromedical considerations

    PubMed Central

    Chiang, Kwo-Tsao; Lee, Shih-Yu; Chu, Hsin

    2015-01-01

    Abstract Dermatofibrosarcoma protuberans (DFSP) is a rare, slow growing, locally infiltrative tumor of intermediate malignancy. It is mostly found on the trunk and head, rarely on hands. The course of evaluation and treatment of a young pilot with DFSP on left middle finger is reported. The clinical issues and aeromedical considerations of this rare tumor is discussed. PMID:27252960

  11. Lack of Association between Membrane-Type 1 Matrix Metalloproteinase Expression and Clinically Relevant Molecular or Morphologic Tumor Characteristics at the Leading Edge of Invasive Colorectal Carcinoma

    PubMed Central

    Arndt, Annette; Kraft, Klaus; Wardelmann, Eva; Steinestel, Konrad

    2015-01-01

    Colorectal cancer (CRC) is one of the leading causes of death from cancer in the western world, but tumor biology and clinical course show great interindividual variation. Molecular and morphologic tumor characteristics, such as KRAS/BRAF mutation status, mismatch repair (MMR) protein expression, tumor growth pattern, and tumor cell budding, have been shown to be of key therapeutic and/or prognostic relevance in CRC. Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a membrane-anchored zinc-binding endopeptidase that is expressed at the leading edge of various invasive carcinomas and promotes tumor cell invasion through degradation of the extracellular matrix. The aim of this study was to investigate possible associations between MT1-MMP expression and molecular tumor characteristics as well as morphologic features of tumor aggressiveness in a consecutive series of 79 CRC tissue samples. However, although MT1-MMP was expressed in 41/79 samples (52%), there was no significant association between MT1-MMP expression and KRAS/BRAF mutation status, MMR protein expression, presence of lymphovascular invasion, tumor growth pattern, tumor-infiltrating lymphocytes, or tumor cell budding in our sample cohort (P > 0.05). Thus, we conclude that although MT1-MMP may play a role in CRC invasion, it is not of key relevance to the current models of CRC invasion and aggressiveness. PMID:26106602

  12. Clinical value of digital image analysis in the diagnosis of urinary bladder cancer, particularly in aggressive tumors: a preliminary report.

    PubMed

    Borkowski, T; Monika Dulewicz, A; Borkowski, A; Piętka, D; Radziszewski, P

    2016-06-01

    The aim of the project was to evaluate the clinical value of a computer analysis of cytological specimen images obtained from urine and bladder washing samples. Three sample types (voided urine, catheterized urine and bladder washing) from 59 patients with primary or recurrent tumor were analyzed. All patients underwent cystoscopy and biopsy or resection. The histological results were compared with the results of the image analyzing computer system of collected urine samples. The consistency between the computer diagnosis and the clinical or histological diagnosis both in the presence and absence of cancer was as follows: 77% for voided urine samples, 72.5% for catheterized urine samples and 78% for bladder washing samples. The specificity of the method at the standard pathology level was 71%, and the sensitivity was 83%. The positive and negative predictive values (PPV and NPV) were 87.5% and 63% respectively. The sensitivity for G3 or CIS or T2 or T3 tumors reached nearly 100%. Computer analysis of urine provided correct diagnoses in cancer and control patients with the sensitivity of 83% and specificity of 71% and gave excellent results in aggressive tumors such as T2, T3, G3 and in CIS. PMID:27543866

  13. Central nervous system recurrence of desmoplastic small round cell tumor following aggressive multimodal therapy: A case report

    PubMed Central

    UMEDA, KATSUTSUGU; SAIDA, SATOSHI; YAMAGUCHI, HIDEKI; OKAMOTO, SHINYA; OKAMOTO, TAKESHI; KATO, ITARU; HIRAMATSU, HIDEFUMI; IMAI, TSUYOSHI; KODAIRA, TAKESHI; HEIKE, TOSHIO; ADACHI, SOUICHI; WATANABE, KEN-ICHIRO

    2016-01-01

    Patients with desmoplastic small round cell tumors (DSRCTs) have an extremely poor outcome despite the use of aggressive therapy. The current study presents the case of 16-year-old male with metastatic DSRCT, in which multimodal therapy, including intensive chemotherapies using frequent autologous stem cell support, gross resection of primary and metastatic lesions, and whole abdominopelvic intensity-modulated radiation therapy, was administered. Subsequent to these treatments, there was no evidence of active disease. However, cerebellar and pineal body lesions, and bone metastasis to the left humerus were detected 1 year and 2 months after the initial diagnosis. Combination chemotherapy with irinotecan and temozolomide was initially effective against the central nervous system (CNS) metastatic lesions; however, the patient succumbed due to progressive CNS disease after seven courses of combination chemotherapy. Additional studies are required to accumulate information regarding CNS recurrence of DSRCT. PMID:26870296

  14. Aggressive tumor growth and clinical evolution in a patient with X-linked acro-gigantism syndrome.

    PubMed

    Naves, Luciana A; Daly, Adrian F; Dias, Luiz Augusto; Yuan, Bo; Zakir, Juliano Coelho Oliveira; Barra, Gustavo Barcellos; Palmeira, Leonor; Villa, Chiara; Trivellin, Giampaolo; Júnior, Armindo Jreige; Neto, Florêncio Figueiredo Cavalcante; Liu, Pengfei; Pellegata, Natalia S; Stratakis, Constantine A; Lupski, James R; Beckers, Albert

    2016-02-01

    X-linked acro-gigantism (X-LAG) syndrome is a newly described disease caused by microduplications on chromosome Xq26.3 leading to copy number gain of GPR101. We describe the clinical progress of a sporadic male X-LAG syndrome patient with an Xq26.3 microduplication, highlighting the aggressive natural history of pituitary tumor growth in the absence of treatment. The patient first presented elsewhere aged 5 years 8 months with a history of excessive growth for >2 years. His height was 163 cm, his weight was 36 kg, and he had markedly elevated GH and IGF-1. MRI showed a non-invasive sellar mass measuring 32.5 × 23.9 × 29.1 mm. Treatment was declined and the family was lost to follow-up. At the age of 10 years and 7 months, he presented again with headaches, seizures, and visual disturbance. His height had increased to 197 cm. MRI showed an invasive mass measuring 56.2 × 58.1 × 45.0 mm, with compression of optic chiasma, bilateral cavernous sinus invasion, and hydrocephalus. His thyrotrope, corticotrope, and gonadotrope axes were deficient. Surgery, somatostatin analogs, and cabergoline did not control vertical growth and pegvisomant was added, although vertical growth continues (currently 207 cm at 11 years 7 months of age). X-LAG syndrome is a new genomic disorder in which early-onset pituitary tumorigenesis can lead to marked overgrowth and gigantism. This case illustrates the aggressive nature of tumor evolution and the challenging clinical management in X-LAG syndrome. PMID:26607152

  15. Aggressive tumor growth and clinical evolution in a patient with X-linked acro-gigantism syndrome.

    PubMed

    Naves, Luciana A; Daly, Adrian F; Dias, Luiz Augusto; Yuan, Bo; Zakir, Juliano Coelho Oliveira; Barra, Gustavo Barcellos; Palmeira, Leonor; Villa, Chiara; Trivellin, Giampaolo; Júnior, Armindo Jreige; Neto, Florêncio Figueiredo Cavalcante; Liu, Pengfei; Pellegata, Natalia S; Stratakis, Constantine A; Lupski, James R; Beckers, Albert

    2016-02-01

    X-linked acro-gigantism (X-LAG) syndrome is a newly described disease caused by microduplications on chromosome Xq26.3 leading to copy number gain of GPR101. We describe the clinical progress of a sporadic male X-LAG syndrome patient with an Xq26.3 microduplication, highlighting the aggressive natural history of pituitary tumor growth in the absence of treatment. The patient first presented elsewhere aged 5 years 8 months with a history of excessive growth for >2 years. His height was 163 cm, his weight was 36 kg, and he had markedly elevated GH and IGF-1. MRI showed a non-invasive sellar mass measuring 32.5 × 23.9 × 29.1 mm. Treatment was declined and the family was lost to follow-up. At the age of 10 years and 7 months, he presented again with headaches, seizures, and visual disturbance. His height had increased to 197 cm. MRI showed an invasive mass measuring 56.2 × 58.1 × 45.0 mm, with compression of optic chiasma, bilateral cavernous sinus invasion, and hydrocephalus. His thyrotrope, corticotrope, and gonadotrope axes were deficient. Surgery, somatostatin analogs, and cabergoline did not control vertical growth and pegvisomant was added, although vertical growth continues (currently 207 cm at 11 years 7 months of age). X-LAG syndrome is a new genomic disorder in which early-onset pituitary tumorigenesis can lead to marked overgrowth and gigantism. This case illustrates the aggressive nature of tumor evolution and the challenging clinical management in X-LAG syndrome.

  16. [Rare malignant tumors of the ovaries in adolescents--clinical aspects in deciding therapeutic aggressiveness].

    PubMed

    Schröder, W; Bau, O

    1990-01-01

    4 patients below the age of 20 years have been treated for a malignant tumor of the ovary during the period November 1, 1984 until April 30, 1988. Dysgerminoma was the diagnosis in two cases, as the third patient suffered from a bilateral malignant teratoma. Burkitt's Lymphoma involved both ovaries primarily in an 17-year-old girl. Retrospectively we analyzed diagnosis, therapy and clinical course of these young patients. Regarding the different histological types of the tumors that have been found we discuss critically current recommendations in therapeutic managements referring chemotherapy and/or radiotherapy. Defined conditions provided surgical treatment, that preserves fertility in early stages of malignant germ cell tumors of adolescent women, may be justified, especially for dysgerminomas. A real benefit relate to survival and quality of life by using chemotherapeutic agents can only be expected, if all prognostic factors are regarded.

  17. Circulating tumor cells exhibit a biologically aggressive cancer phenotype accompanied by selective resistance to chemotherapy.

    PubMed

    Pavese, Janet M; Bergan, Raymond C

    2014-10-01

    With prostate cancer (PCa), circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) portend a poor clinical prognosis. Their unknown biology precludes rational therapeutic design. We demonstrate that CTC and DTC cell lines, established from mice bearing human PCa orthotopic implants, exhibit increased cellular invasion in vitro, increased metastasis in mice, and express increased epithelial to mesenchymal transition biomarkers. Further, they are selectively resistant to growth inhibition by mitoxantrone-like agents. These findings demonstrate that CTC formation is accompanied by phenotypic progression without obligate reversion. Their increased metastatic potential, selective therapeutic resistance, and differential expression of potential therapeutic targets provide a rational basis to test further interventions.

  18. Glycoproteomic Analysis of Prostate Cancer Tissues by SWATH Mass Spectrometry Discovers N-acylethanolamine Acid Amidase and Protein Tyrosine Kinase 7 as Signatures for Tumor Aggressiveness*

    PubMed Central

    Liu, Yansheng; Chen, Jing; Sethi, Atul; Li, Qing K.; Chen, Lijun; Collins, Ben; Gillet, Ludovic C. J.; Wollscheid, Bernd; Zhang, Hui; Aebersold, Ruedi

    2014-01-01

    The identification of biomarkers indicating the level of aggressiveness of prostate cancer (PCa) will address the urgent clinical need to minimize the general overtreatment of patients with non-aggressive PCa, who account for the majority of PCa cases. Here, we isolated formerly N-linked glycopeptides from normal prostate (n = 10) and from non-aggressive (n = 24), aggressive (n = 16), and metastatic (n = 25) PCa tumor tissues and analyzed the samples using SWATH mass spectrometry, an emerging data-independent acquisition method that generates a single file containing fragment ion spectra of all ionized species of a sample. The resulting datasets were searched using a targeted data analysis strategy in which an a priori spectral reference library representing known N-glycosites of the human proteome was used to identify groups of signals in the SWATH mass spectrometry data. On average we identified 1430 N-glycosites from each sample. Out of those, 220 glycoproteins showed significant quantitative changes associated with diverse biological processes involved in PCa aggressiveness and metastasis and indicated functional relationships. Two glycoproteins, N-acylethanolamine acid amidase and protein tyrosine kinase 7, that were significantly associated with aggressive PCa in the initial sample cohort were further validated in an independent set of patient tissues using tissue microarray analysis. The results suggest that N-acylethanolamine acid amidase and protein tyrosine kinase 7 may be used as potential tissue biomarkers to avoid overtreatment of non-aggressive PCa. PMID:24741114

  19. The echographic characteristics of fatty tissues and tumors.

    PubMed

    Behan, M; Kazam, E

    1978-10-01

    Fatty tissues and tumors have been described as characteristically cyst-like on ultrasound examination, with relatively few internal echoes. The authors offer several examples of lipomatous masses and tissues which are markedly echogenic. In vitro studies suggest that this is an inherent property of body fat and is not due to coexistent fibrous tissue or tumor vascularity. The echogenicity of fat has important implications for diagnostic ultrasound: (a) the presence of fat in tissues and masses may be demonstrated by ultrasound, and (b) because the high-level internal echoes blend with the echo pattern of bowel gas and retroperitoneal fat, lipomatous abdominal masses may easily be overlooked.

  20. Decreased expression of H3K27me3 in human ovarian carcinomas correlates with more aggressive tumor behavior and poor patient survival.

    PubMed

    He, W P; Li, Q; Zhou, J; H, Z S; Kung, H F; Guan, X Y; Xie, D; Yang, G F

    2015-01-01

    It has been confirmed that trimethylation of lysine 27 on histone H3 (H3K27me3) plays an important role in epigenetic process of tumorigenesis. However, the status of H3K27me3 in ovarian cancer and its impact on patients' clinicopathologic characteristics and prognosis are unclear. In the present study, the immunohistochemistry (IHC) was utilized to detect protein expression of H3K27me3 in 12 normal ovaries, 26 ovarian cystadenomas, 31 borderline ovarian tumors and 168 ovarian carcinomas by tissue microarray. The association between H3K27me3 expression with clinicopathologic features and patient prognosis were also evaluated using various statistical models. The expression of H3K27me3 was decreased in 2 of 12 (16.7%) cases of the normal ovaries, 8 of 26 (30.8%) cases of cystadenomas, 12 of 31 (38.7%) cases of borderline ovarian tumors, and 93 of 168 (55.4%) cases of primary ovarian carcinomas, respectively (P<0.05). Further correlation analysis suggested that decreased expression of H3K27me3 in ovarian carcinomas was significantly correlated with more advanced pM and FIGO stages (P<0.05). In addition, a significant association between decreased expression of H3K27me3 and shortened patient survival (mean 66 months versus 101 months, p=0.019) was demonstrated by univariate survival analysis of the ovarian carcinoma cohorts. Importantly, H3K27me3 expression provided a significant independent prognostic factor in multivariate analysis (p=0.028). These findings confirmed that decreased expression of H3K27me3 in primary ovarian cancer might be correlated with the acquisition of an invasive and/or aggressive phenotype of tumor, and might serve as an independent biomarker for poor prognosis in patients with ovarian carcinoma.

  1. (1) H NMR spectroscopy of glioblastoma stem-like cells identifies alpha-aminoadipate as a marker of tumor aggressiveness.

    PubMed

    Rosi, Antonella; Ricci-Vitiani, Lucia; Biffoni, Mauro; Grande, Sveva; Luciani, Anna Maria; Palma, Alessandra; Runci, Daniele; Cappellari, Marianna; De Maria, Ruggero; Guidoni, Laura; Pallini, Roberto; Viti, Vincenza

    2015-03-01

    Patients suffering from glioblastoma multiforme (GBM) face a poor prognosis with median survival of about 14 months. High recurrence rate and failure of conventional treatments are attributed to the presence of GBM cells with stem-like properties (GSCs). Metabolite profiles of 42 GSC lines established from the tumor tissue of adult GBM patients were screened with (1) H NMR spectroscopy and compared with human neural progenitor cells from human adult olfactory bulb (OB-NPCs) and from the developing human brain (HNPCs). A first subset (n=12) of GSCs exhibited a dramatic accumulation of the metabolite α-aminoadipate (αAAD), product of the oxidation of α-aminoadipic semialdehyde catalyzed by the ALDH7A1 aldehyde dehydrogenase (ALDH) family in lysine catabolism. αAAD was low/not detectable in a second GSC subset (n=13) with the same neural metabolic profile as well as in a third GSC subset (n=17) characterized by intense lipid signals. Likewise, αAAD was not detected in the spectra of OB-NPCs or HNPCs. Inhibition of mitochondrial ATP synthase by oligomycin treatment revealed that the lysine degradative pathway leading to αAAD formation proceeds through saccharopine, as usually observed in developing brain. Survival curves indicated that high αAAD levels in GSCs significantly correlated with poor patient survival, similarly to prostate and non-small-cell-lung cancers, where activity of ALDH7A1 correlates with tumor aggressiveness. PMID:25581615

  2. Understanding child directed caregiver aggression: An examination of characteristics and predictors associated with perpetration.

    PubMed

    Berkout, Olga V; Kolko, David J

    2016-06-01

    Child physical abuse presents a substantial public health concern with lasting negative consequences for victims. Understanding the variables associated with perpetration can help inform prevention and intervention efforts. The current study examined background and clinical variables in a sample of 195 help-seeking caregivers who were at risk for or had been identified as having engaged in child directed aggression or abuse. We found that caregivers who did (vs. did not) report severe child directed aggression had poorer parenting and reported more drug use. Having a recent allegation of child physical abuse (vs. no allegation) based on official child welfare records was unrelated to parenting, drug and alcohol use, negative affect, parenting stress, or neglect. Structural equation modeling was used to examine the influence of parenting stress on child directed aggression and its effects through negative affect and positive parenting. We found that parenting stress predicted higher negative affect, which was related to greater child directed aggression. Additionally, parenting stress predicted lower positive parenting, which in turn predicted lower child directed aggression. A model including drug and alcohol use did not add to the prediction of child directed aggression. Prediction of neglect using similar variables found that only positive parenting was of import and that parenting stress and negative affect did not contribute to neglect. Implications for future prevention and treatment development efforts with abusive/aggressive caregivers are discussed.

  3. Understanding child directed caregiver aggression: An examination of characteristics and predictors associated with perpetration.

    PubMed

    Berkout, Olga V; Kolko, David J

    2016-06-01

    Child physical abuse presents a substantial public health concern with lasting negative consequences for victims. Understanding the variables associated with perpetration can help inform prevention and intervention efforts. The current study examined background and clinical variables in a sample of 195 help-seeking caregivers who were at risk for or had been identified as having engaged in child directed aggression or abuse. We found that caregivers who did (vs. did not) report severe child directed aggression had poorer parenting and reported more drug use. Having a recent allegation of child physical abuse (vs. no allegation) based on official child welfare records was unrelated to parenting, drug and alcohol use, negative affect, parenting stress, or neglect. Structural equation modeling was used to examine the influence of parenting stress on child directed aggression and its effects through negative affect and positive parenting. We found that parenting stress predicted higher negative affect, which was related to greater child directed aggression. Additionally, parenting stress predicted lower positive parenting, which in turn predicted lower child directed aggression. A model including drug and alcohol use did not add to the prediction of child directed aggression. Prediction of neglect using similar variables found that only positive parenting was of import and that parenting stress and negative affect did not contribute to neglect. Implications for future prevention and treatment development efforts with abusive/aggressive caregivers are discussed. PMID:27131453

  4. Nano-Scaled Particles of Titanium Dioxide Convert Benign Mouse Fibrosarcoma Cells into Aggressive Tumor Cells

    PubMed Central

    Onuma, Kunishige; Sato, Yu; Ogawara, Satomi; Shirasawa, Nobuyuki; Kobayashi, Masanobu; Yoshitake, Jun; Yoshimura, Tetsuhiko; Iigo, Masaaki; Fujii, Junichi; Okada, Futoshi

    2009-01-01

    Nanoparticles are prevalent in both commercial and medicinal products; however, the contribution of nanomaterials to carcinogenesis remains unclear. We therefore examined the effects of nano-sized titanium dioxide (TiO2) on poorly tumorigenic and nonmetastatic QR-32 fibrosarcoma cells. We found that mice that were cotransplanted subcutaneously with QR-32 cells and nano-sized TiO2, either uncoated (TiO2−1, hydrophilic) or coated with stearic acid (TiO2−2, hydrophobic), did not form tumors. However, QR-32 cells became tumorigenic after injection into sites previously implanted with TiO2−1, but not TiO2−2, and these developing tumors acquired metastatic phenotypes. No differences were observed either histologically or in inflammatory cytokine mRNA expression between TiO2−1 and TiO2−2 treatments. However, TiO2−2, but not TiO2−1, generated high levels of reactive oxygen species (ROS) in cell-free conditions. Although both TiO2−1 and TiO2−2 resulted in intracellular ROS formation, TiO2−2 elicited a stronger response, resulting in cytotoxicity to the QR-32 cells. Moreover, TiO2−2, but not TiO2−1, led to the development of nuclear interstices and multinucleate cells. Cells that survived the TiO2 toxicity acquired a tumorigenic phenotype. TiO2-induced ROS formation and its related cell injury were inhibited by the addition of antioxidant N-acetyl-l-cysteine. These results indicate that nano-sized TiO2 has the potential to convert benign tumor cells into malignant ones through the generation of ROS in the target cells. PMID:19815711

  5. Background Predictors and Event-Specific Characteristics of Sexual Aggression Incidents: The Roles of Alcohol and Other Factors

    PubMed Central

    Davis, Kelly Cue; Danube, Cinnamon L.; Stappenbeck, Cynthia A.; Norris, Jeanette; George, William H.

    2014-01-01

    Sexual assault in the United States is an important public health concern. Using prospective longitudinal methods and responses from 217 community men, we examined whether background characteristics predicted subsequent sexual aggression (SA) perpetration during a three month follow-up period. We also examined event-specific characteristics of reported SA occurrences. Consistent with predictions, SA perpetration history, aggressive and impulsive personality traits, rape myth attitudes, and alcohol expectancies predicted SA (both non- and alcohol-involved) at follow-up. Additionally, alcohol-involved assaults occurred more often with casual (vs. steady) partners but were more likely to involve condom use with casual (vs. steady) partners. Results suggest important avenues for future research and SA prevention efforts. PMID:26048213

  6. Arginine vasotocin injection increases probability of calling in cricket frogs, but causes call changes characteristic of less aggressive males.

    PubMed

    Marler, C A; Chu, J; Wilczynski, W

    1995-12-01

    Male cricket frogs, Acris crepitans communicate to males and females using advertisement calls, which are arranged into call groups. Calls at the middle and end, but not beginning of the call group, are modified in response to male-male aggressive interactions. We found in this field study of male cricket frogs in natural breeding choruses that the peptide hormone arginine vasotocin (AVT) not only increased the probability that males called after injections, but also caused modifications in middle and end calls to produce calls characteristic of less aggressive males. Moreover, AVT-injected males showed significantly greater increases in call dominant frequency than saline-injected males, again, a characteristic of less aggressive males. Cricket frog calls are used to both repel males and attract females, thus call changes may relate to male-male and/or male-female interactions. Saline-injected males also demonstrated significant changes in several call traits, including changes that occurred in the beginning and middle calls of the call groups, but not the end calls. AVT appeared to block some call changes produced through handling. These data suggest that AVT can influence acoustic communication in frogs in several ways, including effects on call characteristics and dominant frequency, as well as potentially blocking some handling effects.

  7. Nonodontogenic Tumors of the Jaws.

    PubMed

    Dyalram, Donita; Aslam-Pervez, Nawaf; Lubek, Joshua E

    2016-02-01

    Nonodontogenic tumors of the jaws are common in the pediatric population, accounting for approximately 70% of pediatric jaw tumors. This article focuses on the clinical characteristics and management of the benign nonodontogenic tumors (nonaggressive and aggressive) of the jaws most commonly encountered in children.

  8. Diagnostic Study of Tumor Characteristics in Patients With Ewing's Sarcoma

    ClinicalTrials.gov

    2013-06-20

    Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor

  9. Characteristic endobronchial ultrasound image of hemangiopericytoma/solitary fibrous tumor.

    PubMed

    Chen, Fengshi; Yoshizawa, Akihiko; Okubo, Kenichi; Date, Hiroshi

    2010-09-01

    Hemangiopericytomatous pattern is characteristic of hemangiopericytoma/solitary fibrous tumor (HPC/SFT) and certain histological features might indicate a malignant potential, but the behavior of HPC/SFT is unpredictable. Endobronchial ultrasound (EBUS) is a useful diagnostic device in that the ultrasonographic image can be viewed and the EBUS-transbronchial needle aspiration can obtain a biopsied sample. We herein report a patient undergoing multiple surgical resections of recurrent HPC/SFT. A 74-year-old man had undergone right upper lobectomy for HPC/SFT 15 years ago. He received a partial resection of the left lung and a resection of the anterior mediastinal mass for its recurrences 13 years and six years ago, respectively. He had also undergone surgery for gastric carcinoma two years ago. He then presented with a tumor measuring 3 x 4 cm in the subcarinal area. Preoperative EBUS revealed a tumor with abundant thin-walled vessel-like structures, which was consistent with HPC/SFT. The tumor was completely resected and was finally diagnosed as low-grade malignant HPC/SFT.

  10. Protein Kinase A Effects of an Expressed PRKAR1A Mutation Associated with Aggressive Tumors

    PubMed Central

    Meoli, Elise; Bossis, Ioannis; Cazabat, Laure; Mavrakis, Manos; Horvath, Anelia; Stergiopoulos, Sotiris; Shiferaw, Miriam L.; Fumey, Glawdys; Perlemoine, Karine; Muchow, Michael; Robinson-White, Audrey; Weinberg, Frank; Nesterova, Maria; Patronas, Yianna; Groussin, Lionel; Bertherat, Jérôme; Stratakis, Constantine A.

    2011-01-01

    Most PRKAR1A tumorigenic mutations lead to nonsense mRNA that is decayed; tumor formation has been associated with an increase in type II protein kinase A (PKA) subunits. The IVS6+1G>T PRKAR1A mutation leads to a protein lacking exon 6 sequences [R1αΔ184-236 (R1αΔ6)]. We compared in vitro R1αΔ6 with wild-type (wt) R1α. We assessed PKA activity and subunit expression, phosphorylation of target molecules, and properties of wt-R1α and mutant (mt) R1α; we observed by confocal microscopy R1α tagged with green fluorescent protein and its interactions with Cerulean-tagged catalytic subunit (Cα). Introduction of the R1αΔ6 led to aberrant cellular morphology and higher PKA activity but no increase in type II PKA subunits. There was diffuse, cytoplasmic localization of R1α protein in wt-R1α– and R1αΔ6-transfected cells but the former also exhibited discrete aggregates of R1α that bound Cα; these were absent in R1αΔ6-transfected cells and did not bind Cα at baseline or in response to cyclic AMP. Other changes induced by R1αΔ6 included decreased nuclear Cα. We conclude that R1αΔ6 leads to increased PKA activity through the mt-R1α decreased binding to Cα and does not involve changes in other PKA subunits, suggesting that a switch to type II PKA activity is not necessary for increased kinase activity or tumorigenesis. PMID:18451138

  11. Detection of N-glycolyl GM3 ganglioside in neuroectodermal tumors by immunohistochemistry: an attractive vaccine target for aggressive pediatric cancer.

    PubMed

    Scursoni, Alejandra M; Galluzzo, Laura; Camarero, Sandra; Lopez, Jessica; Lubieniecki, Fabiana; Sampor, Claudia; Segatori, Valeria I; Gabri, Mariano R; Alonso, Daniel F; Chantada, Guillermo; de Dávila, María Teresa G

    2011-01-01

    The N-glycolylated ganglioside NeuGc-GM3 has been described in solid tumors such as breast carcinoma, nonsmall cell lung cancer, and melanoma, but is usually not detected in normal human cells. Our aim was to evaluate the presence of NeuGc-GM3 in pediatric neuroectodermal tumors by immunohistochemistry. Twenty-seven archival cases of neuroblastoma and Ewing sarcoma family of tumors (ESFT) were analyzed. Formalin-fixed, paraffin-embedded tumor samples were cut into 5 μm sections. The monoclonal antibody 14F7, a mouse IgG1 that specifically recognizes NeuGc-GM3, and a peroxidase-labeled polymer conjugated to secondary antibodies were used. Presence of NeuGc-GM3 was evident in 23 of 27 cases (85%), with an average of about 70% of positive tumors cells. Immunoreactivity was moderate to intense in most tumors, showing a diffuse cytoplasmic and membranous staining, although cases of ESFT demonstrated a fine granular cytoplasmic pattern. No significant differences were observed between neuroblastoma with and without NMYC oncogene amplification, suggesting that expression of NeuGc-GM3 is preserved in more aggressive cancers. Until now, the expression of N-glycolylated gangliosides in pediatric neuroectodermal tumors has not been investigated. The present study evidenced the expression of NeuGc-GM3 in a high proportion of neuroectodermal tumors, suggesting its potential utility as a specific target of immunotherapy.

  12. Interleukin-1 and tumor necrosis factor-alpha gene polymorphisms in Turkish patients with localized aggressive periodontitis.

    PubMed

    Guzeldemir, Esra; Gunhan, Meral; Ozcelik, Onur; Tastan, Hakki

    2008-06-01

    Localized aggressive periodontitis (LAgP) is a complex multifactorial periodontal disease to which genetic factors are thought to predispose individuals. Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) are potent immunomodulators and proinflammatory cytokines that have been implicated in the pathogenesis of autoimmune and infectious diseases and proposed to be risk factors for LAgP. Our aim was to investigate IL-1 alpha (+4845), IL-1 beta (+3954), and TNF-alpha (-308) gene polymorphisms in Turkish LAgP patients. We genotyped 31 LAgP patients and 31 healthy controls for IL-1alpha(+4845), IL-1beta(+3954), and TNF-alpha(-308) using standard PCR amplification followed by restriction enzyme digestion and gel electrophoresis. Higher prevalence of heterozygosity for IL-1alpha(+4845) was found in cases (65%) when compared to controls (35%) (P < 0.05). While homozygous allele 1 of IL-1beta(+3954) was the most frequent genotype in cases (62%), no controls were homozygous for this allele (P < 0.001). Homozygous allele 1 was the most common TNF-alpha genotype in both groups, however no significant difference in TNF-alpha genotypes was found between groups. In conclusion, in this Turkish population, susceptibility to LAgP is increased by heterozygosity for allele 1 of IL-1alpha(+4845) or homozygosity for allele 1 of IL-1beta(R+3954). Moreover, IL-1 gene polymorphisms appear to have a role in susceptibility to LAgP, and the above-mentioned genotypes could be an important risk factor for LAgP in the Turkish population.

  13. Overexpression of the growth-hormone-releasing hormone gene in acromegaly-associated pituitary tumors. An event associated with neoplastic progression and aggressive behavior.

    PubMed Central

    Thapar, K.; Kovacs, K.; Stefaneanu, L.; Scheithauer, B.; Killinger, D. W.; Lioyd, R. V.; Smyth, H. S.; Barr, A.; Thorner, M. O.; Gaylinn, B.; Laws, E. R.

    1997-01-01

    The clinical behavior of growth hormone (GH)-producing pituitary tumors is known to vary greatly; however, the events underlying this variability remain poorly understood. Herein we demonstrate that tumor overexpression of the GH-releasing hormone (GHRH) gene is one prognostically informative event associated with the clinical aggressiveness of somatotroph pituitary tumors. Accumulation of GHRH mRNA transcripts was demonstrated in 91 of a consecutive series of 100 somatotroph tumors by in situ hybridization; these findings were corroborated by Northern analysis and reverse transcriptase polymerase chain reaction, and protein translation was confirmed by Western blotting. By comparison, transcript accumulation was absent or negligibly low in 30 normal pituitary glands. GHRH transcripts were found to preferentially accumulate among clinically aggressive tumors. Specifically, GHRH mRNA signal intensity was 1) linearly correlated with Ki-67 tumor growth fractions (r = 0.71; P < 0.001), 2) linearly correlated with preoperative serum GH levels (r = 0.56; p = 0.01), 3) higher among invasive tumors (P < 0.001), and 4) highest in those tumors in which post-operative remission was not achieved (P < 0.001). Using multivariate logistic regression, a model of postoperative remission likelihood was derived wherein remission was defined by the single criterion of suppressibility of GH levels to less than 2 ng/ml during an oral glucose tolerance test. In this outcome model, GHRH mRNA signal intensity proved to be the most important explanatory variable overall, eclipsing any and all conventional clinicopathological predictors as the single most significant predictor of postoperative remission; increases in GHRH mRNA signal were associated with marked declines in remission likelihood. The generalizability of this outcome model was further validated by the model's significant performance in predicting postoperative remission in a random sample of 30 somatotroph tumors treated at

  14. The relationship between brain behavioral systems and the characteristics of the five factor model of personality with aggression among Iranian students

    PubMed Central

    Komasi, Saeid; Saeidi, Mozhgan; Soroush, Ali; Zakiei, Ali

    2016-01-01

    Abstract: Background: Aggression is one of the negative components of emotion and it is usually considered to be the outcome of the activity of the Behavioral Inhibition and the Behavioral Activation System (BIS/BAS): components which can be considered as predisposing factors for personality differences. Therefore, the purpose of this study was to investigate the relationship between brain behavioral systems and the characteristics of the five factor model of personality with aggression among students. Methods: The present study has a correlation descriptive design. The research population included all of the Razi University students in the academic year of 2012-2013. The sampling was carried out with a random stratified method and 360 people (308 female and 52 male) were studied according to a table of Morgan. The study instruments were Buss and Perry Aggression Questionnaire, NEO Personality Inventory (Short Form), and Carver and White scale for BAS/BIS. Finally, SPSS20 was utilized to analyze the data using Pearson correlation, regression analysis, and canonical correlation. Results: The data showed a significant positive relationship between the neurosis and agreeableness personality factors with aggression; but there is a significant negative relationship between the extroversion, openness, and conscientiousness personality factors with aggression. Furthermore, there is a significant positive relationship between all the components of brain behavioral systems (impulsivity, novelty seeking, sensitivity, tender) and aggression. The results of regression analysis indicated the personality characteristics and the brain behavioral systems which can predict 29 percent of the changes to aggression, simultaneously. Conclusions: According to a predictable level of aggressiveness by the personality characteristics and brain behavioral systems, it is possible to identify the personality characteristics and template patterns of brain behavioral systems for the students

  15. In1-ghrelin, a splice variant of ghrelin gene, is associated with the evolution and aggressiveness of human neuroendocrine tumors: Evidence from clinical, cellular and molecular parameters.

    PubMed

    Luque, Raul M; Sampedro-Nuñez, Miguel; Gahete, Manuel D; Ramos-Levi, Ana; Ibáñez-Costa, Alejandro; Rivero-Cortés, Esther; Serrano-Somavilla, Ana; Adrados, Magdalena; Culler, Michael D; Castaño, Justo P; Marazuela, Mónica

    2015-08-14

    Ghrelin system comprises a complex family of peptides, receptors (GHSRs), and modifying enzymes [e.g. ghrelin-O-acyl-transferase (GOAT)] that control multiple pathophysiological processes. Aberrant alternative splicing is an emerging cancer hallmark that generates altered proteins with tumorigenic capacity. Indeed, In1-ghrelin and truncated-GHSR1b splicing variants can promote development/progression of certain endocrine-related cancers. Here, we determined the expression levels of key ghrelin system components in neuroendocrine tumor (NETs) and explored their potential functional role. Twenty-six patients with NETs were prospectively/retrospectively studied [72 samples from primary and metastatic tissues (30 normal/42 tumors)] and clinical data were obtained. The role of In1-ghrelin in aggressiveness was studied in vitro using NET cell lines (BON-1/QGP-1). In1-ghrelin, GOAT and GHSR1a/1b expression levels were elevated in tumoral compared to normal/adjacent tissues. Moreover, In1-ghrelin, GOAT, and GHSR1b expression levels were positively correlated within tumoral, but not within normal/adjacent samples, and were higher in patients with progressive vs. with stable/cured disease. Finally, In1-ghrelin increased aggressiveness (e.g. proliferation/migration) of NET cells. Altogether, our data strongly suggests a potential implication of ghrelin system in the pathogenesis and/or clinical outcome of NETs, and warrant further studies on their possible value for the future development of molecular biomarkers with diagnostic/prognostic/therapeutic value.

  16. In1-ghrelin, a splice variant of ghrelin gene, is associated with the evolution and aggressiveness of human neuroendocrine tumors: Evidence from clinical, cellular and molecular parameters

    PubMed Central

    Gahete, Manuel D.; Ramos-Levi, Ana; Ibáñez-Costa, Alejandro; Rivero-Cortés, Esther; Serrano-Somavilla, Ana; Adrados, Magdalena; Culler, Michael D.; Castaño, Justo P.; Marazuela, Mónica

    2015-01-01

    Ghrelin system comprises a complex family of peptides, receptors (GHSRs), and modifying enzymes [e.g. ghrelin-O-acyl-transferase (GOAT)] that control multiple pathophysiological processes. Aberrant alternative splicing is an emerging cancer hallmark that generates altered proteins with tumorigenic capacity. Indeed, In1-ghrelin and truncated-GHSR1b splicing variants can promote development/progression of certain endocrine-related cancers. Here, we determined the expression levels of key ghrelin system components in neuroendocrine tumor (NETs) and explored their potential functional role. Twenty-six patients with NETs were prospectively/retrospectively studied [72 samples from primary and metastatic tissues (30 normal/42 tumors)] and clinical data were obtained. The role of In1-ghrelin in aggressiveness was studied in vitro using NET cell lines (BON-1/QGP-1). In1-ghrelin, GOAT and GHSR1a/1b expression levels were elevated in tumoral compared to normal/adjacent tissues. Moreover, In1-ghrelin, GOAT, and GHSR1b expression levels were positively correlated within tumoral, but not within normal/adjacent samples, and were higher in patients with progressive vs. with stable/cured disease. Finally, In1-ghrelin increased aggressiveness (e.g. proliferation/migration) of NET cells. Altogether, our data strongly suggests a potential implication of ghrelin system in the pathogenesis and/or clinical outcome of NETs, and warrant further studies on their possible value for the future development of molecular biomarkers with diagnostic/prognostic/therapeutic value. PMID:26124083

  17. Use of extended curettage with osteotomy and fenestration followed by reconstruction with conservation of muscle insertion in the treatment of Enneking stage II locally aggressive bone tumor of the proximal extremities: resection and treatment of bone tumors

    PubMed Central

    2013-01-01

    Background The purpose of this study was to investigate the clinical efficacy of extended resection with osteotomy, fenestration and conservation of muscle (tendon) insertion in the treatment of bone tumors. Methods A total of 15 patients with locally aggressive bone tumors (Enneking stage II) in the adjacent muscle (tendon) insertion of the proximal extremity were enrolled in the present study (mean age of 29 years). Extended curettage of lesions with osteotomy, fenestration and/or conservation of muscle (tendon) insertion and internal fixation with a bone graft or bone cement was performed at stage I. Postsurgical brace protection was used for 4 to 12 weeks and the patients were periodically followed-up by X-ray and functional assessment. Recurrence, postsurgical Enneking score and outcome rating were assessed. Results Treated cases included 15 patients aged 29 ±7.75 years (range, 18 to 42) with a male to female ratio of 8:7. Six had a femoral tumor and nine had a humeral tumor. These tumors comprised three chondroblastomas, five giant-cell tumors and seven aneurysmal bone cysts. Follow-up for 48 ±12.95 months (range, 25 to 72) revealed that 13 of 15 (87%) patients exhibited no recurrence. Local recurrence was observed in a patient with an aneurysmal bone cyst (nine months) and one with a giant-cell tumor (12 months). Mean Enneking scores were 27 ±4.07 (range, 18 to 29). Except for the patient with the recurrent giant-cell tumor, all patients reported good (13%, 2 out of 15) or very good (80%, 12 out of 15) outcomes. Very good outcomes were reported in 92% of patients (12 out of 13) without recurrence. Conclusions The procedures used in this study achieved high clinical efficacy, complete lesion removal, reduced recurrence and good restoration of joint function in patients with primary locally aggressive Enneking stage II bone tumors of the proximal extremities. PMID:23497479

  18. Activation of EGFR, HER2 and HER3 by neurotensin/neurotensin receptor 1 renders breast tumors aggressive yet highly responsive to lapatinib and metformin in mice

    PubMed Central

    Mourra, Najat; Liu, Jin; De Wever, Olivier; Llorca, Frédérique Penault; Cayre, Anne; Kouchkar, Amal; Gompel, Anne; Forgez, Patricia

    2014-01-01

    A present challenge in breast oncology research is to identify therapeutical targets which could impact tumor progression. Neurotensin (NTS) and its high affinity receptor (NTSR1) are up regulated in 20% of breast cancers, and NTSR1 overexpression was shown to predict a poor prognosis for 5 year overall survival in invasive breast carcinomas. Interactions between NTS and NTSR1 induce pro-oncogenic biological effects associated with neoplastic processes and tumor progression. Here, we depict the cellular mechanisms activated by NTS, and contributing to breast cancer cell aggressiveness. We show that neurotensin (NTS) and its high affinity receptor (NTSR1) contribute to the enhancement of experimental tumor growth and metastasis emergence in an experimental mice model. This effect ensued following EGFR, HER2, and HER3 over-expression and autocrine activation and was associated with an increase of metalloproteinase MMP9, HB-EGF and Neuregulin 2 in the culture media. EGFR over expression ensued in a more intense response to EGF on cellular migration and invasion. Accordingly, lapatinib, an EGFR/HER2 tyrosine kinase inhibitor, as well as metformin, reduced the tumor growth of cells overexpressing NTS and NTSR1. All cellular effects, such as adherence, migration, invasion, altered by NTS/NTSR1 were abolished by a specific NTSR1 antagonist. A strong statistical correlation between NTS-NTSR1-and HER3 (p< 0.0001) as well as NTS-NTSR1-and HER3- HER2 (p< 0.001) expression was found in human breast tumors. Expression of NTS/NTSR1 on breast tumoral cells creates a cellular context associated with cancer aggressiveness by enhancing epidermal growth factor receptor activity. We propose the use of labeled NTS/NTSR1 complexes to enlarge the population eligible for therapy targeting HERs tyrosine kinase inhibitor or HER2 overexpression. PMID:25249538

  19. Hyalinizing trabecular tumor of the thyroid gland: characteristic features on ultrasonography.

    PubMed

    Kobayashi, Kaoru; Hirokawa, Mitsuyoshi; Jikuzono, Tomoo; Fukata, Shuji; Amino, Nobuyuki; Miyauchi, Akira; Nakamura, Yasushi

    2007-03-01

    We report a case of hyalinizing trabecular tumor of the thyroid gland and describe the characteristic ultrasonographic features of this tumor. This was a rare tumor of follicular cell origin with a trabecular pattern of growth and marked intratrabecular hyalinization. The tumor had an irregular shape, a delicately jagged border, and hypoechoic and heterogeneous internal echoes on B-mode ultrasonography. Very rich intratumoral blood flow, the so-called "tumor inferno" was evident on power Doppler ultrasonography. In the clinical management of thyroid nodules, clinicians should be aware of this peculiar type of thyroid tumor and its characteristic ultrasonographic findings.

  20. Heparanase-mediated Loss of Nuclear Syndecan-1 Enhances Histone Acetyltransferase (HAT) Activity to Promote Expression of Genes That Drive an Aggressive Tumor Phenotype*

    PubMed Central

    Purushothaman, Anurag; Hurst, Douglas R.; Pisano, Claudio; Mizumoto, Shuji; Sugahara, Kazuyuki; Sanderson, Ralph D.

    2011-01-01

    Heparanase acts as a master regulator of the aggressive tumor phenotype in part by enhancing expression of proteins known to drive tumor progression (e.g. VEGF, MMP-9, hepatocyte growth factor (HGF), and RANKL). However, the mechanism whereby this enzyme regulates gene expression remains unknown. We previously reported that elevation of heparanase levels in myeloma cells causes a dramatic reduction in the amount of syndecan-1 in the nucleus. Because syndecan-1 has heparan sulfate chains and because exogenous heparan sulfate has been shown to inhibit the activity of histone acetyltransferase (HAT) enzymes in vitro, we hypothesized that the reduction in nuclear syndecan-1 in cells expressing high levels of heparanase would result in increased HAT activity leading to stimulation of protein transcription. We found that myeloma cells or tumors expressing high levels of heparanase and low levels of nuclear syndecan-1 had significantly higher levels of HAT activity when compared with cells or tumors expressing low levels of heparanase. High levels of HAT activity in heparanase-high cells were blocked by SST0001, an inhibitor of heparanase. Restoration of high syndecan-1 levels in heparanase-high cells diminished nuclear HAT activity, establishing syndecan-1 as a potent inhibitor of HAT. Exposure of heparanase-high cells to anacardic acid, an inhibitor of HAT activity, significantly suppressed their expression of VEGF and MMP-9, two genes known to be up-regulated following elevation of heparanase. These results reveal a novel mechanistic pathway driven by heparanase expression, which leads to decreased nuclear syndecan-1, increased HAT activity, and up-regulation of transcription of multiple genes that drive an aggressive tumor phenotype. PMID:21757697

  1. Filter Characteristics Influencing Circulating Tumor Cell Enrichment from Whole Blood

    PubMed Central

    Beck, Markus; Terstappen, Leon W. M. M.

    2013-01-01

    A variety of filters assays have been described to enrich circulating tumor cells (CTC) based on differences in physical characteristics of blood cells and CTC. In this study we evaluate different filter types to derive the properties of the ideal filter for CTC enrichment. Between 0.1 and 10 mL of whole blood spiked with cells from tumor cell lines were passed through silicon nitride microsieves, polymer track-etched filters and metal TEM grids with various pore sizes. The recovery and size of 9 different culture cell lines was determined and compared to the size of EpCAM+CK+CD45−DNA+ CTC from patients with metastatic breast, colorectal and prostate cancer. The 8 µm track-etched filter and the 5 µm microsieve had the best performance on MDA-231, PC3-9 and SKBR-3 cells, enriching >80% of cells from whole blood. TEM grids had poor recovery of ∼25%. Median diameter of cell lines ranged from 10.9–19.0 µm, compared to 13.1, 10.7, and 11.0 µm for breast, prostate and colorectal CTC, respectively. The 11.4 µm COLO-320 cell line had the lowest recovery of 17%. The ideal filter for CTC enrichment is constructed of a stiff, flat material, is inert to blood cells, has at least 100,000 regularly spaced 5 µm pores for 1 ml of blood with a ≤10% porosity. While cell size is an important factor in determining recovery, other factors must be involved as well. To evaluate a filtration procedure, cell lines with a median size of 11–13 µm should be used to challenge the system. PMID:23626725

  2. Filter characteristics influencing circulating tumor cell enrichment from whole blood.

    PubMed

    Coumans, Frank A W; van Dalum, Guus; Beck, Markus; Terstappen, Leon W M M

    2013-01-01

    A variety of filters assays have been described to enrich circulating tumor cells (CTC) based on differences in physical characteristics of blood cells and CTC. In this study we evaluate different filter types to derive the properties of the ideal filter for CTC enrichment. Between 0.1 and 10 mL of whole blood spiked with cells from tumor cell lines were passed through silicon nitride microsieves, polymer track-etched filters and metal TEM grids with various pore sizes. The recovery and size of 9 different culture cell lines was determined and compared to the size of EpCAM+CK+CD45-DNA+ CTC from patients with metastatic breast, colorectal and prostate cancer. The 8 µm track-etched filter and the 5 µm microsieve had the best performance on MDA-231, PC3-9 and SKBR-3 cells, enriching >80% of cells from whole blood. TEM grids had poor recovery of ∼25%. Median diameter of cell lines ranged from 10.9-19.0 µm, compared to 13.1, 10.7, and 11.0 µm for breast, prostate and colorectal CTC, respectively. The 11.4 µm COLO-320 cell line had the lowest recovery of 17%. The ideal filter for CTC enrichment is constructed of a stiff, flat material, is inert to blood cells, has at least 100,000 regularly spaced 5 µm pores for 1 ml of blood with a ≤10% porosity. While cell size is an important factor in determining recovery, other factors must be involved as well. To evaluate a filtration procedure, cell lines with a median size of 11-13 µm should be used to challenge the system.

  3. Cryosurgery and acrylic cementation as surgical adjuncts in the treatment of aggressive (benign) bone tumors. Analysis of 25 patients below the age of 21.

    PubMed

    Malawer, M M; Dunham, W

    1991-01-01

    This article reviews the clinical experience with cryosurgery (use of liquid nitrogen) and acrylic cementation (polymethylmethacrylate; PMMA) in the treatment of aggressive, benign bone sarcomas and the biologic basis of this technique. The results of 25 patients below the age of 21 treated by cryosurgery, with an average follow-up period of 60.8 months, are reported. Three approaches to surgical reconstruction were used: Group 1 (four patients) had cryosurgery with no reconstruction, Group 2 (13 patients) had bone graft reconstruction alone, and Group 3 (eight patients) had composite osteosynthesis with internal fixation, bone graft, and/or PMMA. The overall control rate was 96% (one recurrence). The tumor types were giant-cell tumor, chondroblastoma, aneurysmal bone cyst, and malignant giant-cell tumor. Nineteen lesions involved the lower extremity, and six lesions were located in the upper extremity. There were two secondary fractures (8%), one local flap necrosis, and one synovial fistula. There were no infections. Two epiphyseodeses were performed. The functional results were excellent (83%), good (13%), and fair (4%). The technique of composite osteosynthesis is recommended for all large tumors of the lower extremity. Cryosurgical results compare favorably with those obtained by en bloc resection and demonstrate the ability of cryosurgery to eradicate tumors while avoiding the need for extensive resections and reconstructive procedures. PMID:1984931

  4. The Influence of Aggressors' Characteristics on Teachers' Responses to Physical and Relational Aggression

    ERIC Educational Resources Information Center

    Rogowicz, Samantha T.; Del Vecchio, Tamara; Dwyer-Masin, Tanya; Hughes, Elizabeth M.

    2014-01-01

    In the present study, middle school teachers responded to written vignettes describing physical and relational aggressive incidents. The aggressors were male or female children committing an aggressive act against same-sex peers, who were also described as good or bad. Among the results, teachers rated female physical aggression as more serious…

  5. Fetal tumors: prenatal ultrasonographic findings and clinical characteristics

    PubMed Central

    2014-01-01

    The incidence of fetal tumors has been increased due to generalization of prenatal evaluation and improvement of imaging techniques. The early detection of a fetal tumor and understanding of its imaging features are very important for fetal, maternal, and neonatal care. Ultrasonography is usually used for the detection and differential diagnosis of fetal tumors, and magnetic resonance imaging is increasingly being used as a complementary study. Many fetal tumors have different clinical and imaging features compared with pediatric tumors. Although several fetal tumors may mimic other common anomalies, some specific imaging features may carry early accurate diagnosis of fetal tumors, which may alter the prenatal management of a pregnancy and the mode of delivery, and facilitate immediate postnatal treatment. PMID:25116458

  6. Selective participation of c-Jun with Fra-2/c-Fos promotes aggressive tumor phenotypes and poor prognosis in tongue cancer

    PubMed Central

    Gupta, Shilpi; Kumar, Prabhat; Kaur, Harsimrut; Sharma, Nishi; Saluja, Daman; Bharti, Alok C.; Das, Bhudev C.

    2015-01-01

    Tongue squamous cell carcinoma (TSCC) is most aggressive head and neck cancer often associated with HR-HPV infection. The role of AP-1 which is an essential regulator of HPV oncogene expression and tumorigenesis is not reported in tongue cancer. One hundred tongue tissue biopsies comprising precancer, cancer and adjacent controls including two tongue cancer cell lines were employed to study the role of HPV infection and AP-1 family proteins. An exclusive prevalence (28%) of HR-HPV type 16 was observed mainly in well differentiated tongue carcinomas (78.5%). A higher expression and DNA binding activity of AP-1 was observed in tongue tumors and cancer cell lines with c-Fos and Fra-2 as the major binding partners forming the functional AP-1 complex but c-Jun participated only in HPV negative and poorly differentiated carcinoma. Knocking down of Fra-2 responsible for aggressive tongue tumorigenesis led to significant reduction in c-Fos, c-Jun, MMP-9 and HPVE6/E7 expression but Fra-1 and p53 were upregulated. The binding and expression of c-Fos/Fra-2 increased as a function of severity of tongue lesions, yet selective participation of c-Jun appears to promote poor differentiation and aggressive tumorigenesis only in HPV negative cases while HPV infection leads to well differentiation and better prognosis preferably in nonsmokers. PMID:26581505

  7. Aggressive fibromatosis of anterior maxilla

    PubMed Central

    Shetty, Devi C; Urs, Aadithya B; Ahuja, Puneet; Sikka, Seema

    2011-01-01

    Aggressive fibromatosis is a comparitively rare tumor with unpredictable growth and varying local recurrence rates. It does not develop distant metastases but locally it shows an aggressive and infiltrative behavior. Clinically, aggressive fibromatosis manifests as a painless, firm, often rapidly enlarging mass, fixed to underlying bone or soft tissue. It is never encapsulated. Histologically, it is rich in collagen and fibroblastic cells that are devoid of hyperchromatic or atypical nuclei, but with more variable cellularity in different tumor sections. PMID:21731285

  8. The tumoral A genotype of the MGMT rs34180180 single-nucleotide polymorphism in aggressive gliomas is associated with shorter patients' survival.

    PubMed

    Fogli, Anne; Chautard, Emmanuel; Vaurs-Barrière, Catherine; Pereira, Bruno; Müller-Barthélémy, Mélanie; Court, Franck; Biau, Julian; Pinto, Afonso Almeida; Kémény, Jean-Louis; Khalil, Toufic; Karayan-Tapon, Lucie; Verrelle, Pierre; Costa, Bruno Marques; Arnaud, Philippe

    2016-02-01

    Malignant gliomas are the most common primary brain tumors. Grade III and IV gliomas harboring wild-type IDH1/2 are the most aggressive. In addition to surgery and radiotherapy, concomitant and adjuvant chemotherapy with temozolomide (TMZ) significantly improves overall survival (OS). The methylation status of the O(6)-methylguanine-DNA methyltransferase (MGMT) promoter is predictive of TMZ response and a prognostic marker of cancer outcome. However, the promoter regions the methylation of which correlates best with survival in aggressive glioma and whether the promoter methylation status predictive value could be refined or improved by other MGMT-associated molecular markers are not precisely known. In a cohort of 87 malignant gliomas treated with radiotherapy and TMZ-based chemotherapy, we retrospectively determined the MGMT promoter methylation status, genotyped single nucleotide polymorphisms (SNPs) in the promoter region and quantified MGMT mRNA expression level. Each of these variables was correlated with each other and with the patients' OS. We found that methylation of the CpG sites within MGMT exon 1 best correlated with OS and MGMT expression levels, and confirmed MGMT methylation as a stronger independent prognostic factor compared to MGMT transcription levels. Our main finding is that the presence of only the A allele at the rs34180180 SNP in the tumor was significantly associated with shorter OS, independently of the MGMT methylation status. In conclusion, in the clinic, rs34180180 SNP genotyping could improve the prognostic value of the MGMT promoter methylation assay in patients with aggressive glioma treated with TMZ.

  9. The tumoral A genotype of the MGMT rs34180180 single-nucleotide polymorphism in aggressive gliomas is associated with shorter patients' survival.

    PubMed

    Fogli, Anne; Chautard, Emmanuel; Vaurs-Barrière, Catherine; Pereira, Bruno; Müller-Barthélémy, Mélanie; Court, Franck; Biau, Julian; Pinto, Afonso Almeida; Kémény, Jean-Louis; Khalil, Toufic; Karayan-Tapon, Lucie; Verrelle, Pierre; Costa, Bruno Marques; Arnaud, Philippe

    2016-02-01

    Malignant gliomas are the most common primary brain tumors. Grade III and IV gliomas harboring wild-type IDH1/2 are the most aggressive. In addition to surgery and radiotherapy, concomitant and adjuvant chemotherapy with temozolomide (TMZ) significantly improves overall survival (OS). The methylation status of the O(6)-methylguanine-DNA methyltransferase (MGMT) promoter is predictive of TMZ response and a prognostic marker of cancer outcome. However, the promoter regions the methylation of which correlates best with survival in aggressive glioma and whether the promoter methylation status predictive value could be refined or improved by other MGMT-associated molecular markers are not precisely known. In a cohort of 87 malignant gliomas treated with radiotherapy and TMZ-based chemotherapy, we retrospectively determined the MGMT promoter methylation status, genotyped single nucleotide polymorphisms (SNPs) in the promoter region and quantified MGMT mRNA expression level. Each of these variables was correlated with each other and with the patients' OS. We found that methylation of the CpG sites within MGMT exon 1 best correlated with OS and MGMT expression levels, and confirmed MGMT methylation as a stronger independent prognostic factor compared to MGMT transcription levels. Our main finding is that the presence of only the A allele at the rs34180180 SNP in the tumor was significantly associated with shorter OS, independently of the MGMT methylation status. In conclusion, in the clinic, rs34180180 SNP genotyping could improve the prognostic value of the MGMT promoter methylation assay in patients with aggressive glioma treated with TMZ. PMID:26717998

  10. [Transformation of patient-derived tumor xenografts into lymphomas: characteristics, influence factors and precautions].

    PubMed

    Zou, Jianling; Gao, Jing; Shen, Lin

    2016-07-01

    The patient-derived tumor xenografts (PDX) model is an animal model established by directly engrafting fresh tumor tissue of patients into immunodeficiency mice after surgery or biopsy, which plays an important role in the study of tumor biology. However, the transformation of PDX into lymphoma limits the application of this model. The characters of this transformation include that epithelial tumors origin, predorminance of B-cell lymphomas, lost of architectural feature of primary tumor, absence of epithelial tumor markers, and CD45 and CD20 expression. That were characteristics of human B lymphocytes, and possible infection of Epstein-Barr virus(EBV). The biology of primary tumor, EBV infection, inflammation infiltration in primary tumors and the host immune status are the main related factors in this transformation. Therefore, selective xenograft by the detection of EBV infection and inflammation infiltration in primary tumors may be effective methods to prevent lymphomagenesis.

  11. Outgrowth of drug-resistant carcinomas expressing markers of tumor aggression after long term TβRI/II kinase inhibition with LY2109761

    PubMed Central

    Connolly, Erin C.; Saunier, Elise F.; Quigley, David; Luu, Minh Thu; Sapio, Angela De; Hann, Byron; Yingling, Jonathan M.; Akhurst, Rosemary J.

    2011-01-01

    Transforming Growth Factor β (TGF-β) is produced excessively by many solid tumors and can drive malignant progression through multiple effects on the tumor cell and microenvironment. TGF-β signaling pathway inhibitors have shown efficacy in pre-clinical models of metastatic cancer. Here we investigated the effect of systemic LY2109761, a type I /II receptor (TβRI/TβRII) kinase inhibitor, in both a tumor allograft model and in the mouse skin model of de novo chemically-induced carcinogenesis in vivo. Systemic LY2109761 administration disrupted tumor vascular architecture and reduced myofibroblast differentiation of E4 skin carcinoma cells in a tumor allograft. In the 7,12 dimethyl-benzanthracene plus phorbol-myristate-acetate -induced skin chemical carcinogenesis model, acute dosing of established naïve primary carcinomas with LY2109761 (100mg/Kg) every eight hours for ten days (100mg/kg) diminished P-Smad2 levels and marginally decreased the expression of inflammatory and invasive markers. Sustained exposure to LY2109761 (100mg/kg/day) throughout the tumor outgrowth phase had no effect on carcinoma latency or incidence. However, molecular analysis of resultant carcinomas by microarray gene expression, Western blot and immunohistochemistry suggests that long term LY2109761 exposure leads to the outgrowth of carcinomas with elevated P-Smad2 levels that do not respond to drug. This is the first description of acquired resistance to a small molecule inhibitor of the TGF-βRI/II kinase. Resultant carcinomas were more aggressive and inflammatory in nature, with delocalized E-Cadherin and elevated expression of Il23a, laminin V and MMPs. Therefore, TGF-β inhibitors might be clinically useful for applications requiring acute administration, but chronic patient exposure to such drugs should be undertaken with caution. PMID:21282335

  12. The combinatorial activation of the PI3K and Ras/MAPK pathways is sufficient for aggressive tumor formation, while individual pathway activation supports cell persistence

    PubMed Central

    Thompson, Keyata N.; Whipple, Rebecca A.; Yoon, Jennifer R.; Lipsky, Michael; Charpentier, Monica S.; Boggs, Amanda E.; Chakrabarti, Kristi R.; Bhandary, Lekhana; Hessler, Lindsay K.; Martin, Stuart S.; Vitolo, Michele I.

    2015-01-01

    A high proportion of human tumors maintain activation of both the PI3K and Ras/MAPK pathways. In basal-like breast cancer (BBC), PTEN expression is decreased/lost in over 50% of cases, leading to aberrant activation of the PI3K pathway. Additionally, BBC cell lines and tumor models have been shown to exhibit an oncogenic Ras-like gene transcriptional signature, indicating activation of the Ras/MAPK pathway. To directly test how the PI3K and Ras/MAPK pathways contribute to tumorigenesis, we deleted PTEN and activated KRas within non-tumorigenic MCF-10A breast cells. Neither individual mutation was sufficient to promote tumorigenesis, but the combination promoted robust tumor growth in mice. However, in vivo bioluminescence reveals that each mutation has the ability to promote a persistent phenotype. Inherent in the concept of tumor cell dormancy, a stage in which residual disease is present but remains asymptomatic, viable cells with each individual mutation can persist in vivo during a period of latency. The persistent cells were excised from the mice and showed increased levels of the cell cycle arrest proteins p21 and p27 compared to the aggressively growing PTEN−/−KRAS(G12V) cells. Additionally, when these persistent cells were placed into growth-promoting conditions, they were able to re-enter the cell cycle and proliferate. These results highlight the potential for either PTEN loss or KRAS activation to promote cell survival in vivo, and the unique ability of the combined mutations to yield rapid tumor growth. This could have important implications in determining recurrence risk and disease progression in tumor subtypes where these mutations are common. PMID:26497685

  13. The combinatorial activation of the PI3K and Ras/MAPK pathways is sufficient for aggressive tumor formation, while individual pathway activation supports cell persistence.

    PubMed

    Thompson, Keyata N; Whipple, Rebecca A; Yoon, Jennifer R; Lipsky, Michael; Charpentier, Monica S; Boggs, Amanda E; Chakrabarti, Kristi R; Bhandary, Lekhana; Hessler, Lindsay K; Martin, Stuart S; Vitolo, Michele I

    2015-11-01

    A high proportion of human tumors maintain activation of both the PI3K and Ras/MAPK pathways. In basal-like breast cancer (BBC), PTEN expression is decreased/lost in over 50% of cases, leading to aberrant activation of the PI3K pathway. Additionally, BBC cell lines and tumor models have been shown to exhibit an oncogenic Ras-like gene transcriptional signature, indicating activation of the Ras/MAPK pathway. To directly test how the PI3K and Ras/MAPK pathways contribute to tumorigenesis, we deleted PTEN and activated KRas within non-tumorigenic MCF-10A breast cells. Neither individual mutation was sufficient to promote tumorigenesis, but the combination promoted robust tumor growth in mice. However, in vivo bioluminescence reveals that each mutation has the ability to promote a persistent phenotype. Inherent in the concept of tumor cell dormancy, a stage in which residual disease is present but remains asymptomatic, viable cells with each individual mutation can persist in vivo during a period of latency. The persistent cells were excised from the mice and showed increased levels of the cell cycle arrest proteins p21 and p27 compared to the aggressively growing PTEN-/-KRAS(G12V) cells. Additionally, when these persistent cells were placed into growth-promoting conditions, they were able to re-enter the cell cycle and proliferate. These results highlight the potential for either PTEN loss or KRAS activation to promote cell survival in vivo, and the unique ability of the combined mutations to yield rapid tumor growth. This could have important implications in determining recurrence risk and disease progression in tumor subtypes where these mutations are common. PMID:26497685

  14. FBI-1 Is Overexpressed in Gestational Trophoblastic Disease and Promotes Tumor Growth and Cell Aggressiveness of Choriocarcinoma via PI3K/Akt Signaling.

    PubMed

    Mak, Victor C Y; Wong, Oscar G W; Siu, Michelle K Y; Wong, Esther S Y; Ng, Wai-Yan; Wong, Richard W C; Chan, Ka-Kui; Ngan, Hextan Y S; Cheung, Annie N Y

    2015-07-01

    Human placental trophoblasts can be considered pseudomalignant, with tightly controlled proliferation, apoptosis, and invasiveness. Gestational trophoblastic disease (GTD) represents a family of heterogeneous trophoblastic lesions with aberrant apoptotic and proliferative activities and dysregulation of cell signaling pathways. We characterize the oncogenic effects of factor that binds to the inducer of short transcripts of HIV-1 [FBI-1, alias POZ and Krüppel erythroid myeloid ontogenic factor (POKEMON)/ZBTB7A] in GTD and its role in promoting cell aggressiveness in vitro and tumor growth in vivo. IHC studies showed increased nuclear expression of FBI-1, including hydatidiform moles, choriocarcinoma (CCA), and placental site trophoblastic tumor, in GTD. In JAR and JEG-3 CCA cells, ectopic FBI-1 expression opposed apoptosis through repression of proapoptotic genes (eg, BAK1, FAS, and CASP8). FBI-1 overexpression also promoted Akt activation, as indicated by Akt-pS473 phosphorylation. FBI-1 overexpression promoted mobility and invasiveness of JEG-3 and JAR, but not in the presence of the phosphoinositide 3-kinase inhibitor LY294002. These findings suggest that FBI-1 could promote cell migration and invasion via phosphoinositide 3-kinase/Akt signaling. In vivo, nude mice injected with CCA cells with stable FBI-1 knockdown demonstrated reduced tumor growth compared with that in control groups. These findings suggest that FBI-1 is clinically associated with the progression of, and may be a therapeutic target in, GTD, owing to its diverse oncogenic effects on dysregulated trophoblasts. PMID:26093985

  15. FBI-1 Is Overexpressed in Gestational Trophoblastic Disease and Promotes Tumor Growth and Cell Aggressiveness of Choriocarcinoma via PI3K/Akt Signaling.

    PubMed

    Mak, Victor C Y; Wong, Oscar G W; Siu, Michelle K Y; Wong, Esther S Y; Ng, Wai-Yan; Wong, Richard W C; Chan, Ka-Kui; Ngan, Hextan Y S; Cheung, Annie N Y

    2015-07-01

    Human placental trophoblasts can be considered pseudomalignant, with tightly controlled proliferation, apoptosis, and invasiveness. Gestational trophoblastic disease (GTD) represents a family of heterogeneous trophoblastic lesions with aberrant apoptotic and proliferative activities and dysregulation of cell signaling pathways. We characterize the oncogenic effects of factor that binds to the inducer of short transcripts of HIV-1 [FBI-1, alias POZ and Krüppel erythroid myeloid ontogenic factor (POKEMON)/ZBTB7A] in GTD and its role in promoting cell aggressiveness in vitro and tumor growth in vivo. IHC studies showed increased nuclear expression of FBI-1, including hydatidiform moles, choriocarcinoma (CCA), and placental site trophoblastic tumor, in GTD. In JAR and JEG-3 CCA cells, ectopic FBI-1 expression opposed apoptosis through repression of proapoptotic genes (eg, BAK1, FAS, and CASP8). FBI-1 overexpression also promoted Akt activation, as indicated by Akt-pS473 phosphorylation. FBI-1 overexpression promoted mobility and invasiveness of JEG-3 and JAR, but not in the presence of the phosphoinositide 3-kinase inhibitor LY294002. These findings suggest that FBI-1 could promote cell migration and invasion via phosphoinositide 3-kinase/Akt signaling. In vivo, nude mice injected with CCA cells with stable FBI-1 knockdown demonstrated reduced tumor growth compared with that in control groups. These findings suggest that FBI-1 is clinically associated with the progression of, and may be a therapeutic target in, GTD, owing to its diverse oncogenic effects on dysregulated trophoblasts.

  16. Resistin and interleukin-6 exhibit racially-disparate expression in breast cancer patients, display molecular association and promote growth and aggressiveness of tumor cells through STAT3 activation.

    PubMed

    Deshmukh, Sachin K; Srivastava, Sanjeev K; Bhardwaj, Arun; Singh, Ajay P; Tyagi, Nikhil; Marimuthu, Saravanakumar; Dyess, Donna L; Dal Zotto, Valeria; Carter, James E; Singh, Seema

    2015-05-10

    African-American (AA) women with breast cancer (BC) are diagnosed with more aggressive disease, have higher risk of recurrence and poorer prognosis as compared to Caucasian American (CA) women. Therefore, it is imperative to define the factors associated with such disparities to reduce the unequal burden of cancer. Emerging data suggest that inherent differences exist in the tumor microenvironment of AA and CA BC patients, however, its molecular bases and functional impact have remained poorly understood. Here, we conducted cytokine profiling in serum samples from AA and CA BC patients and identified resistin and IL-6 to be the most differentially-expressed cytokines with relative greater expression in AA patients. Resistin and IL-6 exhibited positive correlation in serum levels and treatment of BC cells with resistin led to enhanced production of IL-6. Moreover, resistin also enhanced the expression and phosphorylation of STAT3, and treatment of BC cells with IL-6-neutralizing antibody prior to resistin stimulation abolished STAT3 phosphorylation. In addition, resistin promoted growth and aggressiveness of BC cells, and these effects were mediated through STAT3 activation. Together, these findings suggest a crucial role of resistin, IL-6 and STAT3 in BC racial disparity.

  17. DNMT3B7 Expression Promotes Tumor Progression to a More Aggressive Phenotype in Breast Cancer Cells

    PubMed Central

    Brambert, Patrick R.; Kelpsch, Daniel J.; Hameed, Rabia; Desai, Charmi V.; Calafiore, Gianfranco; Godley, Lucy A.; Raimondi, Stacey L.

    2015-01-01

    Epigenetic changes, such as DNA methylation, have been shown to promote breast cancer progression. However, the mechanism by which cancer cells acquire and maintain abnormal DNA methylation is not well understood. We have previously identified an aberrant splice form of a DNA methyltransferase, DNMT3B7, expressed in virtually all cancer cell lines but at very low levels in normal cells. Furthermore, aggressive MDA-MB-231 breast cancer cells have been shown to express increased levels of DNMT3B7 compared to poorly invasive MCF-7 cells, indicating that DNMT3B7 may have a role in promoting a more invasive phenotype. Using data gathered from The Cancer Genome Atlas, we show that DNMT3B7 expression is increased in breast cancer patient tissues compared to normal tissue. To determine the mechanism by which DNMT3B7 was functioning in breast cancer cells, two poorly invasive breast cancer cell lines, MCF-7 and T-47D, were stably transfected with a DNMT3B7 expression construct. Expression of DNMT3B7 led to hypermethylation and down-regulation of E-cadherin, altered localization of β-catenin, as well as increased adhesion turnover, cell proliferation, and anchorage-independent growth. The novel results presented in this study suggest a role for DNMT3B7 in the progression of breast cancer to a more aggressive state and the potential for future development of novel therapeutics. PMID:25607950

  18. Characteristics and Patterns of Rare Malignancies Published in Rare Tumors.

    PubMed

    Habboush, Jacob; Hollant, Laeticia; Smart, Brigit; Single, Megan; Gaines, Katherine; Patel, Ajaykumar; Miller, Robert

    2016-06-28

    Rare Tumors is an international peer-reviewed medical journal established in 2009. The journal is focused on rare cancers and aims to expand upon current knowledge on their presentation, diagnosis, management, and outcomes. We reviewed the 335 case reports published from 2009 to 2015. We found great diversity in both the country of origin as well as specialty of first authors. Outside of the United States (US) and European Union (EU), there were 20 countries with contributions to the journal. Similarly, there was representation from twelve medical specialties with first authorship of reports. Rare Tumors continues to encourage involvement from physicians across the globe and from all medical disciplines. PMID:27441071

  19. Characteristics and Patterns of Rare Malignancies Published in Rare Tumors

    PubMed Central

    Habboush, Jacob; Hollant, Laeticia; Smart, Brigit; Single, Megan; Gaines, Katherine; Patel, Ajaykumar; Miller, Robert

    2016-01-01

    Rare Tumors is an international peer-reviewed medical journal established in 2009. The journal is focused on rare cancers and aims to expand upon current knowledge on their presentation, diagnosis, management, and outcomes. We reviewed the 335 case reports published from 2009 to 2015. We found great diversity in both the country of origin as well as specialty of first authors. Outside of the United States (US) and European Union (EU), there were 20 countries with contributions to the journal. Similarly, there was representation from twelve medical specialties with first authorship of reports. Rare Tumors continues to encourage involvement from physicians across the globe and from all medical disciplines. PMID:27441071

  20. Angiogenesis dependent characteristics of tumor observed on rabbit VX2 hepatic carcinoma

    PubMed Central

    Guan, Liming

    2015-01-01

    Objective: To evaluate angiogenesis dependent characteristics of carcinoma proliferation, metastasis and to found if there is tumor vascularity architecture defect. Methods: 36 rabbits were random divided into 2 groups: Experimental group: 18 rabbits liver were implanted with VX2 tumor by surgery operation; Control group: 18 experimental rabbits performed the same surgery operation without tumor implantation, the course of tumor growth and blood vessel invasion was observed by autopsy. One slide was used for hematoxylin-eosin (HE) staining, one slide was used for elastic fiber staining by Victoria blue and Ponceau’s histochemical staining, and one slide was used for vascular endothelial cell immunohistochemical staining with biotinylated-ulex europaeus agglutinin I (UEA I); all three slides were observed under an optical microscopic. One additional slide was systematically observed by electron microscopy. SPSS 19.0 software was used for the statistical analyses of the data. Results: The tumor grew acceleration after tumor angiogenesis, volume of original tumors was correlated with vascular caliber. The central tumor found necrosis without enough blood supply while tumor grew rapidly after tumor angiogenesis. The tumor infiltrated into liver blood sinus, blood vessels in hepatic interstitial tissue, the liver capsular vein and important organs metastasis such as lungs, kidneys, abdominal cavity caused rabbits died. The average vascular density count of 18 experimental rabbits under 400 times light microscope were 43.17 ± 8.68/vessels/High Power Field; Tumor vascular diameter all within 200 μm. Vascular elastic fiber staining presented tumor blood vessels internal, external elastic plate intact, vascular endothelial cells organelles of tumor were integrity without endothelial cells architecture defect found by pathologic observation. Conclusion: Proliferation and metastasis of rabbit VX2 hepatic carcinoma was correlated with tumor angiogenesis and no tumor

  1. Case History Report: Immediate Rehabilitation with a Prefabricated Fibula Flap Following Removal of a Locally Aggressive Maxillary Tumor.

    PubMed

    Nkenke, Emeka; Agaimy, Abbas; Vairaktaris, Elefterios; Lell, Michael; von Wilmowsky, Cornelius; Eitner, Stephan

    2016-01-01

    The present clinical case history report describes an interdisciplinary treatment protocol that combines maxillary tumor resection with immediate reconstruction to achieve functional rehabilitation. A fibula flap that received four dental implants and a split-thickness graft epithelial layer was prefabricated for a 31-year-old man. The flap was designed so that it could be adapted to fit in different extents of tumor resection. Resection and immediate reconstruction were successfully performed 6 weeks after flap prefabrication, with the final bar-retained dental prosthesis delivered 4 weeks later. PMID:26757329

  2. Racial and Ethnic disparity in symptomatic breast cancer awareness despite a recent screen: the role of tumor biology and mammography facility characteristics

    PubMed Central

    Mortel, Mylove; Rauscher, Garth H; Murphy, Anne Marie; Hoskins, Kent; Warnecke, Richard B

    2015-01-01

    BACKGROUND In a racially and ethnically diverse sample of recently diagnosed urban breast cancer patients, we examined associations of patient, tumor biology and mammography facility characteristics on the probability of symptomatic discovery of their breast cancer despite a recent prior screening mammogram. METHODS In the Breast Cancer Care in Chicago study, self-reports at interview were used to define patients as having a screen-detected breast cancer or having symptomatic awareness despite a recent screening mammogram (SADRS), in the past one or two years. Patients with symptomatic breast cancer who did not report a recent prior screen were excluded from these analyses. Characteristics associated with more aggressive disease (estrogen and progesterone receptor negative status and higher tumor grade) were abstracted from medical records. Mammogram facility characteristics that might indicate aspects of screening quality were defined and controlled for in some analyses. RESULTS SADRS was more common among nH Black and Hispanic than nH White patients (36% and 42% vs. 25%, respectively, p=0.0004). SADRS was associated with ER/PR negative and higher grade disease. Patients screened at sites that relied on dedicated radiologists, and sites that were breast imaging centers of excellence were less likely to report SADRS. Tumor and facility factors together accounted for two-thirds of the disparity in SADRS (proportion mediated=70%, p=0.02). CONCLUSION Facility resources and tumor aggressiveness explain much of the racial/ethnic disparity in symptomatic breast cancer among recently screened patients. IMPACT: A more equitable distribution of high quality screening would ameliorate but not eliminate this disparity. PMID:26199340

  3. Salmonella-Based Therapy Targeting Indoleamine 2,3-Dioxygenase Coupled with Enzymatic Depletion of Tumor Hyaluronan Induces Complete Regression of Aggressive Pancreatic Tumors.

    PubMed

    Manuel, Edwin R; Chen, Jeremy; D'Apuzzo, Massimo; Lampa, Melanie G; Kaltcheva, Teodora I; Thompson, Curtis B; Ludwig, Thomas; Chung, Vincent; Diamond, Don J

    2015-09-01

    Bacterial-based therapies are emerging as effective cancer treatments and hold promise for refractory neoplasms, such as pancreatic ductal adenocarcinoma (PDAC), which has not shown significant improvement in therapy for more than 25 years. Using a novel combination of shIDO-ST, a Salmonella-based therapy targeting the immunosuppressive molecule indoleamine 2,3-dioxygenase (IDO), with an enzyme, PEGPH20, which depletes extracellular matrix hyaluronan, we observed extended survival with frequent total regression of autochthonous and orthotopic PDAC tumors. This observation was associated with migration and accumulation of activated polymorphonuclear neutrophils (PMN) from spleens into tumors, which was not seen using a scrambled control (shScr-ST). Purified splenic PMNs from PEGPH20/shIDO-ST-treated mice exhibited significant IDO knockdown and were able to kill tumor targets ex vivo through mechanisms involving FasL and serine proteases. In addition, CD8(+) T cells were observed to contribute to late control of pancreatic tumors. Collectively, our data demonstrate that entry of shIDO-ST and PMNs into otherwise impermeable desmoplastic tumors is facilitated by PEGPH20-mediated HA removal, further highlighting an important component of effective treatment for PDAC.

  4. Salmonella-Based Therapy Targeting Indoleamine 2,3-Dioxygenase Coupled with Enzymatic Depletion of Tumor Hyaluronan Induces Complete Regression of Aggressive Pancreatic Tumors

    PubMed Central

    Manuel, Edwin R.; Chen, Jeremy; D'Apuzzo, Massimo; Lampa, Melanie G.; Kaltcheva, Teodora I.; Thompson, Curtis B.; Ludwig, Thomas; Chung, Vincent; Diamond, Don J.

    2015-01-01

    Bacterial-based therapies are emerging as effective cancer treatments and hold promise for refractory neoplasms such as pancreatic ductal adenocarcinoma (PDAC), which has not shown significant improvement in therapy for over twenty-five years. Using a novel combination of shIDO-ST, a Salmonella-based therapy targeting the immunosuppressive molecule indoleamine 2,3-dioxygenase (IDO), with an enzyme, PEGPH20, which depletes extracellular matrix hyaluronan, we observed extended survival with frequent total regression of autochthonous and orthotopic PDAC tumors. This was associated with migration and accumulation of activated polymorphonuclear neutrophils (PMN) from spleens into tumors, which was not observed using a scrambled control (shScr-ST). Purified splenic PMNs from PEGPH20/shIDO-ST-treated mice exhibited significant IDO knockdown and were able to kill tumor targets ex-vivo through mechanisms involving FasL and serine proteases. In addition, CD8+ T cells were observed to contribute to late control of pancreatic tumors. Collectively, our data demonstrate that entry of shIDO-ST and PMNs into otherwise impermeable desmoplastic tumors is facilitated by PEGPH20-mediated HA removal, further highlighting an important component of effective treatment for PDAC. PMID:26134178

  5. Salmonella-Based Therapy Targeting Indoleamine 2,3-Dioxygenase Coupled with Enzymatic Depletion of Tumor Hyaluronan Induces Complete Regression of Aggressive Pancreatic Tumors.

    PubMed

    Manuel, Edwin R; Chen, Jeremy; D'Apuzzo, Massimo; Lampa, Melanie G; Kaltcheva, Teodora I; Thompson, Curtis B; Ludwig, Thomas; Chung, Vincent; Diamond, Don J

    2015-09-01

    Bacterial-based therapies are emerging as effective cancer treatments and hold promise for refractory neoplasms, such as pancreatic ductal adenocarcinoma (PDAC), which has not shown significant improvement in therapy for more than 25 years. Using a novel combination of shIDO-ST, a Salmonella-based therapy targeting the immunosuppressive molecule indoleamine 2,3-dioxygenase (IDO), with an enzyme, PEGPH20, which depletes extracellular matrix hyaluronan, we observed extended survival with frequent total regression of autochthonous and orthotopic PDAC tumors. This observation was associated with migration and accumulation of activated polymorphonuclear neutrophils (PMN) from spleens into tumors, which was not seen using a scrambled control (shScr-ST). Purified splenic PMNs from PEGPH20/shIDO-ST-treated mice exhibited significant IDO knockdown and were able to kill tumor targets ex vivo through mechanisms involving FasL and serine proteases. In addition, CD8(+) T cells were observed to contribute to late control of pancreatic tumors. Collectively, our data demonstrate that entry of shIDO-ST and PMNs into otherwise impermeable desmoplastic tumors is facilitated by PEGPH20-mediated HA removal, further highlighting an important component of effective treatment for PDAC. PMID:26134178

  6. Association of abnormal plasma bilirubin with aggressive HCC phenotype

    PubMed Central

    Carr, Brian I.; Guerra, Vito; Giannini, Edoardo G.; Farinati, Fabio; Ciccarese, Francesca; Rapaccini, Gian Ludovico; Marco, Maria Di; Benvegnù, Luisa; Zoli, Marco; Borzio, Franco; Caturelli, Eugenio; Chiaramonte, Maria; Trevisani, Franco

    2014-01-01

    Background Cirrhosis-related abnormal liver function is associated with predisposition to HCC, features in several HCC classification systems and is an HCC prognostic factor. Aims To examine the phenotypic tumor differences in HCC patients with normal or abnormal plasma bilirubin levels. Methods A 2,416 patient HCC cohort was studied and dichotomized into normal and abnormal plasma bilirubin groups. Their HCC characteristics were compared for tumor aggressiveness features, namely blood AFP levels, tumor size, presence of PVT and tumor multifocality. Results In the total cohort, elevated bilirubin levels were associated with higher AFP levels, increased PVT and multifocality and lower survival, despite similar tumor sizes. When different tumor size terciles were compared, similar results were found, even for small tumor size patients. A multiple logistic regression model for PVT or tumor multifocality showed increased OddsRatios for elevated levels of GGTP, bilirubin and AFP and for larger tumor sizes. Conclusions HCC patients with abnormal bilirubin levels had worse prognosis than patients with normal bilirubin. They also had increased incidence of PVT and tumor multifocality and higher AFP levels, in patients with both small and larger tumors. The results show an association between bilirubin levels and indices of HCC aggressiveness. PMID:24787296

  7. Association of abnormal plasma bilirubin with aggressive hepatocellular carcinoma phenotype.

    PubMed

    Carr, Brian I; Guerra, Vito; Giannini, Edoardo G; Farinati, Fabio; Ciccarese, Francesca; Ludovico Rapaccini, Gian; Di Marco, Maria; Benvegnù, Luisa; Zoli, Marco; Borzio, Franco; Caturelli, Eugenio; Chiaramonte, Maria; Trevisani, Franco

    2014-04-01

    Cirrhosis-related abnormal liver function is associated with predisposition to hepatocellular carcinoma (HCC). It features in several HCC classification systems and is an HCC prognostic factor. The aim of the present study was to examine the phenotypic tumor differences in HCC patients with normal or abnormal plasma bilirubin levels. A 2,416-patient HCC cohort was studied and dichotomized into normal and abnormal plasma bilirubin groups. Their HCC characteristics were compared for tumor aggressiveness features, namely, blood alpha-fetoprotein (AFP) levels, tumor size, presence of portal vein thrombosis (PVT) and tumor multifocality. In the total cohort, elevated bilirubin levels were associated with higher AFP levels, increased PVT and multifocality, and lower survival, despite similar tumor sizes. When different tumor size terciles were compared, similar results were found, even among patients with small tumors. A multiple logistic regression model for PVT or tumor multifocality showed increased odds ratios for elevated levels of gamma glutamyl transpeptidase (GGTP), bilirubin, and AFP and for larger tumor sizes. We conclude that HCC patients with abnormal bilirubin levels had worse prognosis than patients with normal bilirubin. They also had an increased incidence of PVT and tumor multifocality, and higher AFP levels, in patients with both small and larger tumors. The results show an association between bilirubin levels and indices of HCC aggressiveness. PMID:24787296

  8. Association of abnormal plasma bilirubin with aggressive hepatocellular carcinoma phenotype.

    PubMed

    Carr, Brian I; Guerra, Vito; Giannini, Edoardo G; Farinati, Fabio; Ciccarese, Francesca; Ludovico Rapaccini, Gian; Di Marco, Maria; Benvegnù, Luisa; Zoli, Marco; Borzio, Franco; Caturelli, Eugenio; Chiaramonte, Maria; Trevisani, Franco

    2014-04-01

    Cirrhosis-related abnormal liver function is associated with predisposition to hepatocellular carcinoma (HCC). It features in several HCC classification systems and is an HCC prognostic factor. The aim of the present study was to examine the phenotypic tumor differences in HCC patients with normal or abnormal plasma bilirubin levels. A 2,416-patient HCC cohort was studied and dichotomized into normal and abnormal plasma bilirubin groups. Their HCC characteristics were compared for tumor aggressiveness features, namely, blood alpha-fetoprotein (AFP) levels, tumor size, presence of portal vein thrombosis (PVT) and tumor multifocality. In the total cohort, elevated bilirubin levels were associated with higher AFP levels, increased PVT and multifocality, and lower survival, despite similar tumor sizes. When different tumor size terciles were compared, similar results were found, even among patients with small tumors. A multiple logistic regression model for PVT or tumor multifocality showed increased odds ratios for elevated levels of gamma glutamyl transpeptidase (GGTP), bilirubin, and AFP and for larger tumor sizes. We conclude that HCC patients with abnormal bilirubin levels had worse prognosis than patients with normal bilirubin. They also had an increased incidence of PVT and tumor multifocality, and higher AFP levels, in patients with both small and larger tumors. The results show an association between bilirubin levels and indices of HCC aggressiveness.

  9. Down-regulation of cytoplasmic PLZF correlates with high tumor grade and tumor aggression in non-small cell lung carcinoma.

    PubMed

    Xiao, Guang-Qian; Li, Faqian; Findeis-Hosey, Jennifer; Hyrien, Ollivier; Unger, Pamela D; Xiao, Lu; Dunne, Richard; Kim, Eric S; Yang, Qi; McMahon, Loralee; Burstein, David E

    2015-11-01

    There are currently no effective prognostic biomarkers for lung cancer. Promyelocytic leukemia zinc finger (PLZF), a transcriptional repressor, has a role in cell cycle progression and tumorigenicity in various cancers. The expression and value of PLZF in lung carcinoma, particularly in the subclass of non-small cell lung carcinoma (NSCLC), has not been studied. Our aim was to study the immunohistochemical expression of PLZF in lung adenocarcinoma and squamous cell carcinoma and correlate the alteration of PLZF expression with tumor differentiation, lymph node metastasis, tumor stage, and overall survival. A total of 296 NSCLCs being mounted on tissue microarray (181 adenocarcinomas and 91 squamous cell carcinomas) were investigated. Moderate to strong expression of PLZF was found in the cytoplasm of all the nonneoplastic respiratory epithelium and most (89.9%) well-differentiated adenocarcinoma. The proportions of moderately differentiated, poorly differentiated adenocarcinoma, and paired lymph node adenocarcinoma metastases that demonstrated negative or only weak PLZF reactivity were 75.6%, 97.2%, and 89.9%, respectively. The expression of PLZF in squamous cell carcinoma was mostly weak or absent and significantly lower than that in adenocarcinoma of the same grade (P < .0005). The loss of cytoplasmic PLZF strongly correlated with high tumor grade and lymph node metastasis in both squamous carcinoma and adenocarcinoma (P < .0001). Down-regulation of PLZF also correlated with higher tumor stage and shorter overall survival (P < .05). These results support a prognostic value for loss of cytoplasmic PLZF expression in the stratification of NSCLC and a possible role of cytoplasmic shift and down-regulation of PLZF in the pathogenesis of NSCLC.

  10. Hypothalamic tumor

    MedlinePlus

    ... occur at any age. They are often more aggressive in adults than in children. In adults, tumors ... The treatment depends on how aggressive the tumor is, and whether it is a glioma or another type of cancer. Treatment may involve combinations of surgery, radiation , ...

  11. Protease Activated Receptors 1 and 2 Correlate Differently with Breast Cancer Aggressiveness Depending on Tumor ER Status

    PubMed Central

    Lidfeldt, Jon; Bendahl, Pär-Ola; Forsare, Carina; Malmström, Per; Fernö, Mårten; Belting, Mattias

    2015-01-01

    Experimental models implicate protease activated receptors (PARs) as important sensors of the proteolytic tumor microenvironment during breast cancer development. However, the role of the major PARs, PAR-1 and PAR-2, in human breast tumors remains to be elucidated. Here, we have investigated how PAR-1 and PAR-2 protein expression correlate with established clinicopathological variables and patient outcome in a well-characterized cohort of 221 breast cancer patients. Univariable and multivariable hazard ratios (HR) were estimated by the Cox proportional hazards model, distant disease-free survival (DDFS) and overall survival by the Kaplan–Meier method, and survival in different strata was determined by the log-rank test. Associations between PARs and clinicopathological variables were analyzed using Pearson’s χ2-test. We find that PAR-2 associates with DDFS (HR = 3.1, P = 0.003), whereas no such association was found with PAR-1 (HR = 1.2, P = 0.6). Interestingly, the effect of PAR-2 was confined to the ER-positive sub-group (HR = 5.5, P = 0.003 vs. HR = 1.2 in ER-negative; P = 0.045 for differential effect), and PAR-2 was an independent prognostic factor specifically in ER-positive tumors (HR = 3.9, P = 0.045). On the contrary, PAR-1 correlated with worse prognosis specifically in the ER-negative group (HR = 2.6, P = 0.069 vs. HR = 0.5, P = 0.19 in ER-positive; P = 0.026 for differential effect). This study provides novel insight into the respective roles of PAR-1 and PAR-2 in human breast cancer and suggests a hitherto unknown association between PARs and ER signaling that warrants further investigation. PMID:26244666

  12. Recurrent NTRK1 Gene Fusions Define a Novel Subset of Locally Aggressive Lipofibromatosis-like Neural Tumors.

    PubMed

    Agaram, Narasimhan P; Zhang, Lei; Sung, Yun-Shao; Chen, Chun-Liang; Chung, Catherine T; Antonescu, Cristina R; Fletcher, Christopher Dm

    2016-10-01

    The family of pediatric fibroblastic and myofibroblastic proliferations encompasses a wide spectrum of pathologic entities with overlapping morphologies and ill-defined genetic abnormalities. Among the superficial lesions, lipofibromatosis (LPF), composed of an admixture of adipose tissue and fibroblastic elements, in the past has been variously classified as infantile fibromatosis or fibrous hamartoma of infancy. In this regard, we have encountered a group of superficial soft tissue tumors occurring in children and young adults, with a notably infiltrative growth pattern reminiscent of LPF, variable cytologic atypia, and a distinct immunoprofile of S100 protein and CD34 reactivity, suggestive of neural differentiation. SOX10 and melanocytic markers were negative in all cases tested. In contrast, a control group of classic LPF displayed bland, monomorphic histology and lacked S100 protein immunoreactivity. To define the pathogenetic abnormalities in these seemingly distinctive groups, we performed RNA sequencing for fusion gene discovery in 2 cases each, followed by screening for any novel alterations identified in a larger cohort representing both entities. The 2 index LPF-like neural tumors (LPF-NT) showed TPR-NTRK1 and TPM3-NTRK1 gene fusions, which were further validated by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction. Subsequent FISH screening of 14 LPF-NT identified recurrent NTRK1 gene rearrangements in 10 (71%) cases. Of the NTRK1-negative LPF-NT cases, 1 case each showed ROS1 and ALK gene rearrangements. In contrast, none of the 25 classic LPFs showed NTRK1 gene rearrangements, although regional abnormalities were noted in the 1q21-22 region by FISH in a majority of cases. Furthermore, NTRK1 immunostaining was positive only in NTRK1-rearranged S100-positive LPF-NT but negative in classic LPF. These results suggest that NTRK1 oncogenic activation through gene fusion defines a novel and distinct subset of soft

  13. Recurrent NTRK1 Gene Fusions Define a Novel Subset of Locally Aggressive Lipofibromatosis-like Neural Tumors.

    PubMed

    Agaram, Narasimhan P; Zhang, Lei; Sung, Yun-Shao; Chen, Chun-Liang; Chung, Catherine T; Antonescu, Cristina R; Fletcher, Christopher Dm

    2016-10-01

    The family of pediatric fibroblastic and myofibroblastic proliferations encompasses a wide spectrum of pathologic entities with overlapping morphologies and ill-defined genetic abnormalities. Among the superficial lesions, lipofibromatosis (LPF), composed of an admixture of adipose tissue and fibroblastic elements, in the past has been variously classified as infantile fibromatosis or fibrous hamartoma of infancy. In this regard, we have encountered a group of superficial soft tissue tumors occurring in children and young adults, with a notably infiltrative growth pattern reminiscent of LPF, variable cytologic atypia, and a distinct immunoprofile of S100 protein and CD34 reactivity, suggestive of neural differentiation. SOX10 and melanocytic markers were negative in all cases tested. In contrast, a control group of classic LPF displayed bland, monomorphic histology and lacked S100 protein immunoreactivity. To define the pathogenetic abnormalities in these seemingly distinctive groups, we performed RNA sequencing for fusion gene discovery in 2 cases each, followed by screening for any novel alterations identified in a larger cohort representing both entities. The 2 index LPF-like neural tumors (LPF-NT) showed TPR-NTRK1 and TPM3-NTRK1 gene fusions, which were further validated by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction. Subsequent FISH screening of 14 LPF-NT identified recurrent NTRK1 gene rearrangements in 10 (71%) cases. Of the NTRK1-negative LPF-NT cases, 1 case each showed ROS1 and ALK gene rearrangements. In contrast, none of the 25 classic LPFs showed NTRK1 gene rearrangements, although regional abnormalities were noted in the 1q21-22 region by FISH in a majority of cases. Furthermore, NTRK1 immunostaining was positive only in NTRK1-rearranged S100-positive LPF-NT but negative in classic LPF. These results suggest that NTRK1 oncogenic activation through gene fusion defines a novel and distinct subset of soft

  14. A Large Scale Study of the Psychometric Characteristics of the IBR Modified Overt Aggression Scale: Findings and Evidence for Increased Self-Destructive Behaviors in Adult Females with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Cohen, Ira L.; Tsiouris, John A.; Flory, Michael J.; Kim, Soh-Yule; Freedland, Robert; Heaney, Glenn; Pettinger, Jill; Brown, W. Ted

    2010-01-01

    The psychometric characteristics of the IBR Modified Overt Aggression Scale were studied in over 2,000 people with Intellectual Disability (ID). Reliability ranged from good to excellent. Aggression toward others and objects was highest in the youngest adults, in those in the moderate to severe range of ID, and in those with an autism spectrum…

  15. Inattention/hyperactivity and aggression from early childhood to adolescence: Heterogeneity of trajectories and differential influence of family environment characteristics

    PubMed Central

    JESTER, JENNIFER M.; NIGG, JOEL T.; ADAMS, KENNETH; FITZGERALD, HIRAM E.; PUTTLER, LEON I.; WONG, MARIA M.; ZUCKER, ROBERT A.

    2008-01-01

    In attention/hyperactivity and aggressive behavior problems were measured in 335 children from school entry throughout adolescence, at 3-year intervals. Children were participants in a high-risk prospective study of substance use disorders and comorbid problems. A parallel process latent growth model found aggressive behavior decreasing throughout childhood and adolescence, whereas inattentive/hyperactive behavior levels were constant. Growth mixture modeling, in which developmental trajectories are statistically classified, found two classes for inattention/hyperactivity and two for aggressive behavior, resulting in a total of four trajectory classes. Different influences of the family environment predicted development of the two types of behavior problems when the other behavior problem was held constant. Lower emotional support and lower intellectual stimulation by the parents in early childhood predicted membership in the high problem class of inattention/hyperactivity when the trajectory of aggression was held constant. Conversely, conflict and lack of cohesiveness in the family environment predicted membership in a worse developmental trajectory of aggressive behavior when the inattention/hyperactivity trajectories were held constant. The implications of these findings for the development of inattention/hyperactivity and for the development of risk for the emergence of substance use disorders are discussed. PMID:15971762

  16. Strong Expression of Hypoxia-Inducible Factor-1α (HIF-1α) Is Associated with Axl Expression and Features of Aggressive Tumors in African Breast Cancer

    PubMed Central

    Nalwoga, Hawa; Ahmed, Lavina; Arnes, Jarle B.; Wabinga, Henry; Akslen, Lars A.

    2016-01-01

    Purpose Inhibition of hypoxia-inducible factor (HIF) and Axl receptor tyrosine kinase is being evaluated for targeted therapy in solid tumors. Both HIF-1α and Axl influence tumor growth and metastatic potential, and they have been linked to treatment failure in many cancers. However, there is a lack of reports on HIF-1α expression in African breast cancer, which has a poor prognosis, and novel treatment targets must therefore be established. Here, we aimed to evaluate HIF-1α in relation to Axl expression, angiogenesis markers, and other tumor characteristics in a series of African breast cancer. Methods Using immunohistochemistry, we examined 261 invasive breast cancers on tissue microarrays for HIF-1α and Axl as well as several other markers, and a subset of 185 cases had information on VEGF (vascular endothelial growth factor) expression, microvessel density (MVD), proliferating microvessel density (pMVD) and vascular proliferation index (VPI) for important comparisons. Results Strong HIF-1α expression was associated with increased Axl (p = 0.007), VEGF (p<0.0005), and p53 (p = 0.032) expression, as well as high tumor cell proliferation by Ki-67 (p = 0.006), and high tumor grade (p = 0.003). Tumors with strong HIF-1α expression had significantly higher MVD (p = 0.019) and higher pMVD (p = 0.027) than tumors with weak expression. Conclusions High HIF-1α expression is significantly associated with Axl and VEGF expression, and with markers of poor prognosis in this series of breast cancer, suggesting HIF-1α and Axl as potential therapeutic targets in African breast cancer. PMID:26760782

  17. Maternal and Birth Characteristics and Childhood Embryonal Solid Tumors: A Population-Based Report from Brazil

    PubMed Central

    de Paula Silva, Neimar; de Souza Reis, Rejane; Garcia Cunha, Rafael; Pinto Oliveira, Júlio Fernando; Santos, Marceli de Oliveira; Pombo-de-Oliveira, Maria S.; de Camargo, Beatriz

    2016-01-01

    Background Several maternal and birth characteristics have been reported to be associated with an increased risk of many childhood cancers. Our goal was to evaluate the risk of childhood embryonal solid tumors in relation to pre- and perinatal characteristics. Methods A case-cohort study was performed using two population-based datasets, which were linked through R software. Tumors were classified as central nervous system (CNS) or non-CNS-embryonal (retinoblastoma, neuroblastoma, renal tumors, germ cell tumors, hepatoblastoma and soft tissue sarcoma). Children aged <6 years were selected. Adjustments were made for potential confounders. Odds ratios (OR) with 95% confidence intervals (CI) were computed by unconditional logistic regression analysis using SPSS. Results Males, high maternal education level, and birth anomalies were independent risk factors. Among children diagnosed older than 24 months of age, cesarean section (CS) was a significant risk factor. Five-minute Apgar ≤8 was an independent risk factor for renal tumors. A decreasing risk with increasing birth order was observed for all tumor types except for retinoblastoma. Among children with neuroblastoma, the risk decreased with increasing birth order (OR = 0.82 (95% CI 0.67–1.01)). Children delivered by CS had a marginally significantly increased OR for all tumors except retinoblastoma. High maternal education level showed a significant increase in the odds for all tumors together, CNS tumors, and neuroblastoma. Conclusion This evidence suggests that male gender, high maternal education level, and birth anomalies are risk factors for childhood tumors irrespective of the age at diagnosis. Cesarean section, birth order, and 5-minute Apgar score were risk factors for some tumor subtypes. PMID:27768709

  18. High levels of class III β-tubulin expression are associated with aggressive tumor features in breast cancer

    PubMed Central

    LEBOK, PATRICK; ÖZTÜRK, MELIKE; HEILENKÖTTER, UWE; JAENICKE, FRITZ; MÜLLER, VOLKMAR; PALUCHOWSKI, PETER; GEIST, STEFAN; WILKE, CHRISTIAN; BURANDT, EICKE; LEBEAU, ANNETTE; WILCZAK, WALDEMAR; KRECH, TILL; SIMON, RONALD; SAUTER, GUIDO; QUAAS, ALEXANDER

    2016-01-01

    Overexpression of class III β-tubulin (TUBB3), a factor that confers dynamic properties to microtubules, is a candidate biomarker for resistance to microtubule-targeting chemotherapeutics in breast and other types of solid cancer. Discrepant results from previous studies, with respect to the association of TUBB3 expression levels with breast cancer phenotype and patient prognosis, prompted the present study to investigate TUBB3 expression in a large cohort of breast cancer cases, with available clinical follow-up data. A preexisting breast cancer prognosis tissue microarray, containing a single 0.6 mm tissue core from each of 2,197 individual patients with breast cancer, was analyzed for TUBB3 expression by immunohistochemistry. The results of the present study revealed that TUBB3 expression was less frequent in lobular breast cancer cases (34%), compared with that of cancer cases of alternative histologies, including breast cancer of no special type (60%; P<0.0001). High TUBB3 positivity was associated with high tumor grade (P<0.0001), negativity for estrogen (P<0.0001) and progesterone receptors (P<0.004), as well as the presence of human epidermal growth factor 2 amplification (P<0.0001) and a triple-negative phenotype (P<0.0001). TUBB3 overexpression was additionally associated with reduced patient survival if all breast cancer cases of any histology were jointly analyzed (P=0.0088); however this link was not evident in the subset of breast cancer cases of no special type, or in a multivariate analysis including the established prognostic factors of tumor stage, grade and nodal stage. In conclusion, the present study demonstrated that TUBB3 overexpression was associated with adverse features of breast cancer, and that TUBB3 may possess a distinct role in lobular breast cancer cases, compared with alternative histological subtypes. The results of the present study do not support a clinically relevant role for TUBB3 as a prognostic marker in breast cancer. PMID

  19. Characteristic Formation of Hyaluronan-Cartilage Link Protein-Proteoglycan Complex in Salivary Gland Tumors.

    PubMed

    Kuwabara, Hiroko; Nishikado, Akira; Hayasaki, Hana; Isogai, Zenzo; Yoneda, Masahiko; Kawata, Ryo; Hirose, Yoshinobu

    2016-01-01

    Hyaluronan (HA) and its binding molecules, cartilage link protein (LP) and proteoglycan (PG), are structural components of the hydrated extracellular matrix. Because these molecules play important roles in the tumor microenvironment, we examined the distribution of HA, LP, versican, and aggrecan in salivary gland tumors using histochemical and immunohistochemical methods, including double staining. LP was present in pleomorphic adenoma (PA) and adenoid cystic carcinoma (ACC) tissues, and aggrecan was absent in the malignant tumors that we investigated. LP colocalized with both HA and aggrecan in the chondromyxoid matrix of PA, suggesting the presence of a HA-LP-aggrecan complex. Furthermore, the HA-LP-versican complex could be observed in the pseudocystic space of the cribriform structures in ACC. The characteristic HA-LP-PG complex in PA and ACC might play a role in the behavior of tumors, and immunohistochemical analysis of these molecules could represent a diagnostic adjunct for salivary gland tumors.

  20. [Aggressive fibromatoses in orthopedics].

    PubMed

    Adler, C P; Stock, D

    1986-01-01

    Aggressive fibromatoses which may develop either in soft tissue or in the bone present considerable problems for the pathologist trying to establish a diagnosis as well as for the radiologist and surgeon. In radiographs, a destruction of the soft and osseous tissue is seen which suggests a malignant tumor. Histologically a monomorphic connective tissue prevails in the biopsy showing no essential signs of malignancy. Under pathoanatomical aspects often a benign proliferation of the connective tissue is assumed. Surgically the tumor may either be removed in a too radical and mutilating way, or the excision may remain incomplete. Two cases of desmoplastic bone fibroma (aggressive fibromatosis in the ulna and in the sacrum) are described in which the complete tumor removal led to healing, whereas the incomplete excision of the tumor resulted in recurrences. Aggressive fibromatosis represents a semimalignant tumor which has a locally destructive and invasive growth tendency but does not metastasize. The various fibromatoses are defined with regard to their biological growth tendency and the therapeutic consequences are discussed.

  1. High level of CFTR expression is associated with tumor aggression and knockdown of CFTR suppresses proliferation of ovarian cancer in vitro and in vivo.

    PubMed

    Xu, Jiao; Yong, Min; Li, Jia; Dong, Xiaojing; Yu, Tinghe; Fu, Xiao; Hu, Lina

    2015-05-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) belongs to the ATP-binding cassette (ABC) transporter family, members of which are involved in various types of cancer. The relationship between CFTR and ovarian cancer remains to be elucidated. The aim of the present study was to investigate the expression of CFTR in human ovarian cancer tissues and its clinical significance in the progression of ovarian cancer. The role of CFTR in the malignant invasion, migration and proliferation of ovarian cancer in vitro and in vivo was also investigated. Immunohistochemical staining analysis was performed to detect the expression of CFTR in 83 cases of human epithelial ovarian cancer specimens. Moreover, SKOV3 and A2780 stable cell lines containing shRNA gene specific for CFTR were established. Cell proliferation and motility were observed and compared with CFTR-RNAi cells. Tumorigenicity of CFTR-RNAi cells was investigated by tumor xenograft experiments conducted subcutaneously in nude mice. The expresssion of CFTR in ovarian cancer was significantly higher than that in benign ovarian tumor and normal ovaries (P<0.05). In ovarian cancer, CFTR expression was significantly associated with advanced FIGO stage, poor histopathological grade and serum Ca-125 (P<0.05). Furthermore, we observed that CFTR staining was stronger in the serous type as compared to the other types (P<0.05). Compared with the negative control, decreased cell invasion, migration, proliferation, adhesion and colony formation were observed in CFTR-RNAi cells in vitro. In vivo, tumorigenic abilities of CFTR-RNAi cells were significantly repressed compared with that of the control groups. CFTR overexpression may play an important role in the development and progression of ovarian cancer. Additionally, the downregulation of CFTR suppresses aggressive malignant biological behaviors of ovarian cancer cells in vitro and in vivo. PMID:25738998

  2. Examination of Personal and Socio-Behavioral Characteristics as Predictors of Aggressive Behavioral Tendencies of University Students

    ERIC Educational Resources Information Center

    Yang, Heewon; An, Dongsu

    2013-01-01

    The purpose of this study was to examine university students' aggressive behavioral tendencies. Students ("n" = 405) at a Midwestern University, were selected as study sample. This study hypothesized that demographic variables (e.g., age, gender, class standing, racial minority status, and G.P.A. score) and study variables (e.g.,…

  3. Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor characteristics in the European Prospective Investigation into Cancer and Nutrition.

    PubMed

    Ose, Jennifer; Fortner, Renée T; Rinaldi, Sabina; Schock, Helena; Overvad, Kim; Tjonneland, Anne; Hansen, Louise; Dossus, Laure; Fournier, Agnes; Baglietto, Laura; Romieu, Isabelle; Kuhn, Elisabetta; Boeing, Heiner; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Masala, Giovanna; Sieri, Sabina; Tumino, Rosario; Sacerdote, Carlotta; Mattiello, Amalia; Ramon Quiros, Jose; Obón-Santacana, Mireia; Larrañaga, Nerea; Chirlaque, María-Dolores; Sánchez, María-José; Barricarte, Aurelio; Peeters, Petra H; Bueno-de-Mesquita, H Bas; Onland-Moret, N Charlotte; Brändstedt, Jenny; Lundin, Eva; Idahl, Annika; Weiderpass, Elisabete; Gram, Inger T; Lund, Eiliv; Kaw, Kay-Tee; Travis, Ruth C; Merritt, Melissa A; Gunther, Marc J; Riboli, Elio; Kaaks, Rudolf

    2015-01-15

    The role of endogenous androgens and sex hormone-binding globulin (SHBG) in ovarian carcinogenesis is poorly understood. Epithelial invasive ovarian cancer (EOC) is a heterogeneous disease and there are no prospective data on endogenous androgens and EOC risk by tumor characteristics (histology, grade, stage) or the dualistic model of ovarian carcinogenesis (i.e. type I vs. type II, leading to less or more aggressive tumors). We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort evaluating androgens and SHBG and invasive EOC risk by tumor characteristics. Female participants who provided a blood sample and were not using exogenous hormones at blood donation were eligible (n = 183,257). A total of 565 eligible women developed EOC; two controls (n = 1,097) were matched per case. We used multivariable conditional logistic regression models. We observed no association between androgens, SHBG and EOC overall. A doubling of androstenedione reduced risk of serous carcinomas by 21% (odds ratio (OR)log2 = 0.79, 95% confidence interval [CI] = [0.64-0.97]). Moreover, associations differed for low-grade and high-grade carcinomas, with positive associations for low-grade and inverse associations for high-grade carcinomas (e.g. androstenedione: low grade: ORlog2 = 1.99 [0.98-4.06]; high grade: ORlog2 = 0.75 [0.61-0.93], phet ≤ 0.01), similar associations were observed for type I/II tumors. This is the first prospective study to evaluate androgens, SHBG and EOC risk by tumor characteristics and type I/II status. Our findings support a possible role of androgens in ovarian carcinogenesis. Additional studies exploring this association are needed.

  4. Quantification of Liver Tumors Using Statistical Characteristics of Ultrasonic RF Signals

    NASA Astrophysics Data System (ADS)

    Chono, Tomoaki; Ito, Masayasu

    We propose a method for quantification of liver tumors using statistical characteristics of ultrasonic RF signals. Parameters of K distribution show the characteristics of a soft tissue. The proposed method of chi-square test(CST) can estimate the most appropriate parameters of K distribution, which are fitted to an observed amplitude distribution. Method of moment(MOM), method combining maximum likelihood and MOM(ML/MOM), and CST are compared on simulated RF signals. The CST is applied to RF signals of liver tumors including 38 hepatocellular carcinomas(malignancy) and 12 hepatic hemangiomas(benignancy). The accuracy of discriminant analysis are 78% and 50% for malignancy and benignancy, respectively.

  5. Underexpression of LKB1 tumor suppressor is associated with enhanced Wnt signaling and malignant characteristics of human intrahepatic cholangiocarcinoma.

    PubMed

    Wang, Jinghan; Zhang, Keqiang; Wang, Jinhui; Wu, Xiwei; Liu, Xiyong; Li, Bin; Zhu, Yan; Yu, Yong; Cheng, Qingbao; Hu, Zhenli; Guo, Chao; Hu, Shuya; Mu, Bing; Tsai, Chun-Hao; Li, Jie; Smith, Lynne; Yang, Lu; Liu, Qi; Chu, Peiguo; Chang, Vincent; Zhang, Baihe; Wu, Mengchao; Jiang, Xiaoqing; Yen, Yun

    2015-08-01

    Intrahepatic cholangiocarcinoma (ICC) is a rare and highly aggressive malignancy. In this study, we identified the presence of gene deletion and missense mutation leading to inactivation or underexpression of liver kinase B1 (LKB1) tumor suppressor and excluded the involvement of LKB1 gene hypermethylation in ICC tissues. Immunohistochemical analysis showed that LKB1 was underexpressed in a portion of 326 ICC tissues compared to their adjacent normal tissues. By statistical analysis underexpression of LKB1 in ICC tissues significantly correlated with poor survival and malignant disease characteristics in ICC patients. Moreover, we showed that knockdown of LKB1 significantly enhanced growth, migration, and invasion of three LKB1-competent ICC cell lines. Global transcriptional profiling analysis identified multiple malignancy-promoting genes, such as HIF-1α, CD24, Talin1, Vinculin, Wnt5, and signaling pathways including Hedgehog, Wnt/β-catenin, and cell adhesion as novel targets of LKB1 underexpression in ICC cells. Furthermore, knockdown of LKB1 gene expression dramatically enhanced Wnt/β-catenin signaling in ICC cells, while an inverse correlation between LKB1 and nuclear β-catenin was observed in ICC tissues. Our findings suggest a novel mechanism for ICC carcinogenesis in which LKB1 underexpression enhances multiple signaling pathways including Wnt/β-catenin to promote disease progression.

  6. Signaling aggression.

    PubMed

    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.

  7. The Characteristics of AD/HD Symptoms, Self-Esteem, and Aggression among Serious Juvenile Offenders in Japan

    ERIC Educational Resources Information Center

    Matsuura, Naomi; Hashimoto, Toshiaki; Toichi, Motomi

    2010-01-01

    Eighty-three inmates of a correctional facility, who committed serious offences, participated in this study. They were all male and aged 14-17 years, with a mean age of 15.5 (SD=1.21) years. Eighty-six age- and sex-matched controls were enrolled. Some psychological questionnaires such as on self-esteem and aggression were conducted in both groups.…

  8. Tumor necrosis factor-α G-308A (rs1800629) polymorphism and aggressive periodontitis susceptibility: a meta-analysis of 16 case-control studies

    PubMed Central

    Wei, Xue-Mei; Chen, Yong-Ji; Wu, Lan; Cui, Li-Jun; Hu, Ding-Wei; Zeng, Xian-Tao

    2016-01-01

    Association between tumor necrosis factor-α (TNF-α) G-308A (rs1800629) polymorphism and susceptibility to aggressive periodontitis (AgP) were inconsistent, hence we performed this meta-analysis to clarify the association between them using Comprehensive Meta-Analysis v2.2 software. 16 case-control studies were searched from the PubMed, Embase and CNKI databases up to February 2, 2015. The meta-analysis showed a significantly increased risk in A vs. G (OR = 1.23, 95%CI = 1.04–1.44), AA vs. GG (OR = 2.07, 95%CI = 1.11–3.87), and AA vs. AG+GG genetic models (OR = 2.09, 95%CI = 1.13–3.86); however, the non-significantly increased risk was shown in AG vs. GG (OR = 1.06, 95%CI = 0.85–1.32) and AA+AG vs. GG genetic models (OR = 1.06, 95%CI = 0.85–1.31). Cumulative analysis showed that the association changed from non-significant to significant with new studies accumulated and the CIs became more and more narrow, sensitivity analysis indicated results were statistically robust. Stratified analyses of confirmed of HWE, Asians, Caucasians, and population-based controls obtained results similar to that of overall analysis. There was no evidence of publication bias. In summary, current evidence demonstrates that TNF-a G-308A polymorphism might be associated with AgP susceptibility, especially in Asians and Caucasians. PMID:26750615

  9. IRF1 and NF-kB restore MHC class I-restricted tumor antigen processing and presentation to cytotoxic T cells in aggressive neuroblastoma.

    PubMed

    Lorenzi, Silvia; Forloni, Matteo; Cifaldi, Loredana; Antonucci, Chiara; Citti, Arianna; Boldrini, Renata; Pezzullo, Marco; Castellano, Aurora; Russo, Vincenzo; van der Bruggen, Pierre; Giacomini, Patrizio; Locatelli, Franco; Fruci, Doriana

    2012-01-01

    Neuroblastoma (NB), the most common solid extracranial cancer of childhood, displays a remarkable low expression of Major Histocompatibility Complex class I (MHC-I) and Antigen Processing Machinery (APM) molecules, including Endoplasmic Reticulum (ER) Aminopeptidases, and poorly presents tumor antigens to Cytotoxic T Lymphocytes (CTL). We have previously shown that this is due to low expression of the transcription factor NF-kB p65. Herein, we show that not only NF-kB p65, but also the Interferon Regulatory Factor 1 (IRF1) and certain APM components are low in a subset of NB cell lines with aggressive features. Whereas single transfection with either IRF1, or NF-kB p65 is ineffective, co-transfection results in strong synergy and substantial reversion of the MHC-I/APM-low phenotype in all NB cell lines tested. Accordingly, linked immunohistochemistry expression patterns between nuclear IRF1 and p65 on the one hand, and MHC-I on the other hand, were observed in vivo. Absence and presence of the three molecules neatly segregated between high-grade and low-grade NB, respectively. Finally, APM reconstitution by double IRF1/p65 transfection rendered a NB cell line susceptible to killing by anti MAGE-A3 CTLs, lytic efficiency comparable to those seen upon IFN-γ treatment. This is the first demonstration that a complex immune escape phenotype can be rescued by reconstitution of a limited number of master regulatory genes. These findings provide molecular insight into defective MHC-I expression in NB cells and provide the rational for T cell-based immunotherapy in NB variants refractory to conventional therapy.

  10. CD44 standard and variant isoform expression in human epidermal skin tumors is not correlated with tumor aggressiveness but down-regulated during proliferation and tumor de-differentiation.

    PubMed

    Seelentag, W K; Günthert, U; Saremaslani, P; Futo, E; Pfaltz, M; Heitz, P U; Roth, J

    1996-06-21

    CD44 isoforms have been reported to be involved in tumor invasion and metastasis formation. Normal human skin expresses high levels of CD44 isoforms, but little is known about their expression in epidermal skin tumors. Expression of CD44 standard (CD44s) and variant exon (CD44v3, -v4, -v5, -v6, -v9)-encoded gene products has been studied in 74 benign, semi-malignant and malignant human epithelial skin tumors using a panel of well-characterized, variant exon-specific monoclonal antibodies (MAbs). Sensitivity and resolution of the immunohistochemical staining in paraffin sections was substantially improved by using microwave-based antigen retrieval and an optimized streptavidin-biotin-peroxidase technique. Immunostaining was evaluated semi-quantitatively and correlated with tumor type and degree of histological differentiation by non-parametric statistical tests. Furthermore, the relationship between CD44 expression and cellular proliferation rate as defined by the Ki-67 antigen was analyzed in basal cell carcinomas. We found a significant correlation between tumor type and CD44 isoform expression. Basal cell carcinomas exhibited the weakest staining and keratoacanthomas the strongest. Squamous cell carcinomas ranged in between, with a tendency to down-regulate CD44 expression upon de-differentiation. In basal cell carcinomas, an inverse relationship between CD44 expression and proliferation rate was directly demonstrated at the cellular level using double immunolabelling. Our data indicate that qualitative and quantitative changes in CD44 splicevariant expression in human skin tumors do not correlate with invasive and metastatic potential but are rather related to the degree of tumor differentiation. PMID:8682591

  11. Wilms Tumor

    MedlinePlus

    ... diagnosis, and the condition, or histology , of the cancer cells when observed under a microscope. "Favorable" histology is associated with a good chance of a cure; tumors with "unfavorable" histology are more aggressive and ...

  12. The renal tumor morphological characteristics that affect surgical planning for laparoscopic or open partial nephrectomy.

    PubMed

    Funahashi, Yasuhito; Murotani, Kenta; Yoshino, Yasushi; Sassa, Naoto; Ishida, Shohei; Gotoh, Momokazu

    2015-02-01

    The purpose of this study is to investigate the morphological characteristics of renal tumors which affect the surgeons' decision-making for the selection of open or laparoscopic partial nephrectomy. We included 147 patients who underwent partial nephrectomy for renal masses with elective indications in this study. Laparoscopic partial nephrectomy (LPN) and open partial nephrectomy (OPN) were performed in 72 and 75 patients, respectively. Preoperative trans-sectional images were used to assess tumor characteristics such as tumor size, endophyticity, distance from the sinus, distance from the kidney equator, hilar designation, inside designation, and R.E.N.A.L. nephrometry score. Univariate logistic regression analyses demonstrated that tumor size, endophyticity, distance from the sinus, hilar designation, inside designation, and R.E.N.A.L. nephrometry score were associated with decision of laparoscopic partial nephrectomy. Among these factors, multiple regression analyses showed that endophyticity (odds ratio = 0.92, p = 0.007) and distance from the sinus (odds ratio = 1.201, p < 0.001) had statistically significant associations with the type of operation performed. ROC analyses demonstrated cut-off values of 16 mm for endophyticity (sensitivity 69%, specificity 77%) and of 4 mm for distance from the sinus (sensitivity 79%, specificity 65%) for predicting the selection of laparoscopic surgery. In conclusion, this study revealed that endophyticity and distance from the sinus were important for the surgical planning of partial nephrectomy.

  13. Hypoxia in Head and Neck Tumors: Characteristics and Development during Therapy

    PubMed Central

    Bittner, Martin-Immanuel; Grosu, Anca-Ligia

    2013-01-01

    Cancers of the head and neck are a malignancy causing a considerable health burden. In head and neck cancer patients, tumor hypoxia has been shown to be an important predictor of response to therapy and outcome. Several imaging modalities can be used to determine the amount and localization of tumor hypoxia. Especially PET has been used in a number of studies analyzing this phenomenon. However, only few studies have reported the characteristics and development during (chemoradio-) therapy. Yet, the characterization of tumor hypoxia in the course of treatment is of great clinical importance. Successful delineation of hypoxic subvolumes could make an inclusion into radiation treatment planning feasible, where dose painting is hypothesized to improve the tumor control probability. So far, hypoxic subvolumes have been shown to undergo changes during therapy; in most cases, a reduction in tumor hypoxia can be seen, but there are also differing observations. In addition, the hypoxic subvolumes have mostly been described as geographically rather stable. However, studies specifically addressing these issues are needed to provide more data regarding these initial findings and the hypotheses connected with them. PMID:24010122

  14. Biological characteristics of a novel giant cell tumor cell line derived from spine.

    PubMed

    Zhou, Zhenhua; Li, Yan; Xu, Leqin; Wang, Xudong; Chen, Su; Yang, Cheng; Xiao, Jianru

    2016-07-01

    Giant cell tumor of bone(GCTB) is a special bone tumor for it consists of various cell types, and its biological characteristics is different from common benign or malignant neoplasm. In the present study, we report the biological features of a primary Asian GCTB cell line named GCTB28. We analyzed extensive properties of the GCTB28 cells including morphological observations, growth, cell cycle, karyotype, proliferation, proteins expression, surface biomarker verification, and tumorigenicity in nude mice. We found that the stromal cells of GCTB were endowed with self-renewal capacity and played dominant roles in GCTB development. Moreover, we confirmed that GCTB cells can be CD33(-)CD14(-) phenotype which was not in accord with previous study. This study provides an in vitro model system to investigate pathogenic mechanisms and molecular characteristics of GCTB and also provides a useful tool for researching the therapeutic targeting of GCTB.

  15. Extensive Surgery Best for an Aggressive Brain Cancer

    MedlinePlus

    ... fullstory_159415.html Extensive Surgery Best for an Aggressive Brain Cancer: Study Although larger procedure carries more ... News) -- When it comes to battling a particularly aggressive form of brain tumor, more extensive surgeries may ...

  16. Neuroendocrine Tumors of the Urinary Bladder According to the 2016 World Health Organization Classification: Molecular and Clinical Characteristics.

    PubMed

    Kouba, Erik; Cheng, Liang

    2016-09-01

    Neuroendocrine neoplasms of the urinary bladder are a rare type of tumor that account for a small percentage of urinary bladder neoplasms. These tumors of the urinary bladder range from well-differentiated neuroendocrine neoplasms (carcinoids) to the more aggressive subtypes such as small cell carcinoma. Despite the rarity of the neuroendocrine tumors of the bladder, there has been substantial investigation into the underlying genomic, molecular, and the cellular alterations within this group of neoplasms. Accordingly, these findings are increasingly incorporated into the understanding of clinical aspects of these neoplasms. In this review, we provide an overview of recent literature related to the 2016 World Health Organization Classification of Neuroendocrine Tumors of the Urinary Bladder. Particular emphasis is placed on molecular alterations and recently described gene expression. The neuroendocrine tumors of the urinary bladder are subdivided into four subtypes. Similar to their pulmonary and other extrapulmonary site counterparts, these have different degrees of neuroendocrine differentiation and morphological features. The clinical aspects of four subtypes of neuroendocrine tumor are discussed with emphasis of the most recent developments in diagnosis, treatment, and prognosis. An understanding of molecular basis of neuroendocrine tumors will provide a base of knowledge for future investigations into this group of unusual bladder neoplasms.

  17. [Insular carcinoma of the thyroid. An uncommon but aggressive neoplasm].

    PubMed

    Naranjo-Gómez, José Manuel; Folqué-Gómez, Emilio; Moreno-Mata, Nicolás; Moldes-Rodríguez, Milagros; Martínez-Martínez, Patricia; González-Aragoneses, Federico; Orusco-Palomino, Eduardo

    2005-04-01

    Insular carcinoma of the thyroid is an infrequent entity, named in 1984 by Carcangiu when he described its characteristic histology. Clinically and morphologically it is considered to be in an intermediate position between well-differentiated carcinoma of the thyroid (papillary or follicular) and undifferentiated or anaplastic carcinoma of the thyroid. However, most authors believe it to be an independent entity. The prognosis of this tumor is worse than that of classic carcinoma of the thyroid, and most authors advise aggressive therapy, which in some cases can achieved prolonged survival. We describe 2 patients who experienced recurrence after treatment for the primary tumor. The recurrences were treated but the clinical courses differed.

  18. Understanding Aggression.

    ERIC Educational Resources Information Center

    Scott, J. P.

    Research in many fields of the social and biological sciences indicates that there are ecological, cultural, social, psychological, physiological, and genetic causes of aggression. The agonistic behavior system, which adapts to situations of social conflict, includes several patterns of conduct ranging from overt fighting to complete passivity. In…

  19. Recent advances in systemic therapy for gastrointestinal neuroendocrine tumors.

    PubMed

    Pelley, R J; Bukowski, R M

    1999-01-01

    Neuroendocrine tumors of the gastrointestinal tract are rare tumors which can be classified as amine precursor uptake and decarboxylation tumors (APU-Domas). Although the majority of clinically apparent tumors are malignant, they are frequently slow growing. Despite this characteristic, they may generate disabling hormonal syndromes requiring aggressive treatment to achieve palliation. Recent advances in understanding the pathophysiology of these tumors has led to better medical therapy with chemotherapeutic agents, somatostatin analogues, and biologic therapies. This review will update the recent efforts in systemic therapies of the gastrointestinal neuroendocrine tumors.

  20. Adjuvant Therapies and Patient and Tumor Characteristics Associated With Survival of Adult Patients With Adrenocortical Carcinoma

    PubMed Central

    Williams, Andrew R.; Sabolch, Aaron; Jolly, Shruti; Miller, Barbra S.; Hammer, Gary D.

    2014-01-01

    Context: Adrenocortical carcinoma is a rare malignant endocrine neoplasia. Studies regarding outcome and prognostic factors rely on fairly small studies. Here we summarize the experience with patients with a diagnosis of adrenocortical carcinoma from a large tertiary referral center. Objective: The objective of the study was to identify prognostic factors in patients with adrenocortical carcinoma and evaluate adjuvant treatment strategies. Design: Patient data were collected in a retrospective single-center study. Epidemiological, patient, and tumor characteristics were analyzed for prognostic factors regarding overall and recurrence-free survival in Cox regression models (multivariable and univariable). Results: Three hundred ninety-one adult patients with the diagnosis of adrenocortical carcinoma were identified. Median overall survival was 35.2 months. Cortisol production [hazard ratio (HR) 1.4, HR 1.5], tumor stage (HR stage 3 of 2.1 and 2.1, HR stage 4 of 4.8), and tumor grade (HR 2.4 and 2.0) were identified as negative prognostic factors (HR for death, HR for recurrence). Mitotane therapy increases recurrence-free survival, an effect that was significantly further improved by adjuvant radiation therapy but did not impact overall survival. Patients with open adrenalectomy had improved overall survival. Conclusions: This study increases the evidence for adverse risk factors (cortisol production, high tumor stage, and high tumor grade) and suggests the following therapy approach: adrenocortical carcinoma patients should be treated with open adrenalectomy. Adjuvant therapy, particularly mitotane therapy in conjunction with radiation, should be considered to delay tumor recurrence. PMID:24302750

  1. Circulating tumor cells exhibit stem cell characteristics in an orthotopic mouse model of colorectal cancer

    PubMed Central

    Niemietz, Thomas; Betzler, Alexander M.; Nanduri, Lahiri K.; Bork, Ulrich; Kahlert, Christoph; Thepkaysone, May-Linn; Swiersy, Anka; Büchler, Markus W.; Reissfelder, Christoph; Weitz, Jürgen; Rahbari, Nuh N.

    2016-01-01

    The prognosis of colorectal cancer (CRC) is closely linked to the occurrence of distant metastases, which putatively develop from circulating tumor cells (CTCs) shed into circulation by the tumor. As far more CTCs are shed than eventually metastases develop, only a small subfraction of CTCs harbor full tumorigenic potential. The aim of this study was to further characterize CRC-derived CTCs to eventually identify the clinically relevant subfraction of CTCs. We established an orthotopic mouse model of CRC which reliably develops metastases and CTCs. We were able to culture the resulting CTCs in vitro, and demonstrated their tumor-forming capacity when re-injected into mice. The CTCs were then subjected to qPCR expression profiling, revealing downregulation of epithelial and proliferation markers. Genes associated with cell-cell adhesion (claudin-7, CD166) were significantly downregulated, indicating a more metastatic phenotype of CTCs compared to bulk tumor cells derived from hepatic metastases. The stem cell markers DLG7 and BMI1 were significantly upregulated in CTC, indicating a stem cell-like phenotype and increased capacity of tumor formation and self-renewal. In concert with their in vitro and in vivo tumorigenicity, these findings indicate stem cell properties of mouse-derived CTCs. In conclusion, we developed an orthotopic mouse model of CRC recapitulating the process of CRC dissemination. CTCs derived from this model exhibit stem-cell like characteristics and are able to form colonies in vitro and tumors in vivo. Our results provide new insight into the biology of CRC-derived CTCs and may provide new therapeutic targets in the metastatic cascade of CRC. PMID:27029058

  2. Several murine metastasizing tumors possess a cysteine proteinase with cancer procoagulant characteristics.

    PubMed

    Falanga, A; Bolognese Dalessandro, A P; Casali, B; Roncaglioni, M C; Donati, M B

    1987-06-15

    Cancer Procoagulant (CP), a cysteine proteinase which triggers blood coagulation by directly activating Factor X (FX) in the absence of Factor VII (F VII), has recently been isolated from rabbit V2 carcinoma and biochemically characterized. We have studied the procoagulant activity of tissue extracts from 4 murine experimental tumors in order to define whether or not a F VII-independent activity with cysteine proteinase characteristics was present. The tumors studied were: Lewis lung carcinoma (3LL), B16 melanoma (B16), JW sarcoma (JWS) and the M4 variant of the mFS6 fibrosarcoma (M4). Extracts from 3LL, B16 and JWS tumor initiated coagulation in both the presence and absence of F VII, their procoagulant activity was sensitive to iodoacetamide (1 mM) and mercury chloride (0.1 mM). The procoagulant of M4 extract was dependent on the presence of F VII and was not significantly affected by the cysteine proteinase inhibitors. An Ouchterlony double immunodiffusion study showed immunological cross-reactivity of all but M4 extracts to a polyclonal antibody to purified CP. The present study suggests that the procoagulant(s) present in the murine tumors 3LL, B16 and JWS are enzymatically and immunologically indistinguishable from cancer procoagulant of the rabbit V2 carcinoma.

  3. Hypoxia-inducible factor 1–mediated characteristic features of cancer cells for tumor radioresistance

    PubMed Central

    Harada, Hiroshi

    2016-01-01

    Tumor hypoxia has been attracting increasing attention in the fields of radiation biology and oncology since Thomlinson and Gray detected hypoxic cells in malignant solid tumors and showed that they exert a negative impact on the outcome of radiation therapy. This unfavorable influence has, at least partly, been attributed to cancer cells acquiring a radioresistant phenotype through the activation of the transcription factor, hypoxia-inducible factor 1 (HIF-1). On the other hand, accumulating evidence has recently revealed that, even though HIF-1 is recognized as an important regulator of cellular adaptive responses to hypoxia, it may not become active and induce tumor radioresistance under hypoxic conditions only. The mechanisms by which HIF-1 is activated in cancer cells not only under hypoxic conditions, but also under normoxic conditions, through cancer-specific genetic alterations and the resultant imbalance in intermediate metabolites have been summarized herein. The relevance of the HIF-1–mediated characteristic features of cancer cells, such as the production of antioxidants through reprogramming of the glucose metabolic pathway and cell cycle regulation, for tumor radioresistance has also been reviewed. PMID:26983985

  4. Tumor

    MedlinePlus

    ... plants (aflatoxins) Excessive sunlight exposure Genetic problems Obesity Radiation exposure Viruses Types of tumors known to be caused by viruses are: Cervical cancer (human papillomavirus) Hepatocellular carcinoma (hepatitis B and hepatitis C ...

  5. Malignant characteristics of circulating tumor cells and corresponding primary tumor in a patient with esophageal squamous cell carcinoma before and after surgery.

    PubMed

    Ren, Chuanli; He, Ping; Zhang, Jinqiang; Zheng, Zhaoxu; Qiao, Yuanyuan; Zhao, Xiaohang

    2011-04-01

    We report the malignant characteristics of circulating tumor cells (CTCs) and the corresponding molecular features of the primary tumor in a patient with esophageal squamous cell carcinoma (ESCC). A 70-year-old male patient was diagnosed with TNM stage T3N0M0 ESCC. Before surgery, seven intact CTCs and 12 CTCs with a fragmented membrane were detected in 7.5 mL of peripheral blood by immunofluorescence staining. One week after radical resection of the primary tumor, four CTCs were identified in 7.5ml peripheral blood. All CTCs were confirmed as having a malignant phenotype by chromosomal analysis and routine cell staining. Ninety percent of the CTCs were found to have polysomic chromosomes 8 and 20 by fluorescence in situ hybridization (FISH). Immunofluorescence analysis showed that all of the primary tumor cells detected were cytokeratin8/18/19 (CK8/18/19)-positive, but only 1% were CD133-positive. The serum CA19-9 and CEA level were normal in the process of diseases. The patient died 6 months after surgery as a result of lung metastases and other complications. The results of this study suggest that the dynamics and malignant characteristics of both CTCs and the corresponding primary tumor during the disease process may predict tumor burden and the risk of relapse and metastasis.

  6. Fibropapillomatosis in green turtles Chelonia mydas in Brazil: characteristics of tumors and virus.

    PubMed

    Rodenbusch, C R; Baptistotte, C; Werneck, M R; Pires, T T; Melo, M T D; de Ataíde, M W; Testa, P; Alieve, M M; Canal, C W

    2014-10-16

    Fibropapillomatosis (FP) is a benign neoplasia that affects physiological functions of sea turtles and may lead to death. High prevalence of FP in sea turtle populations has prompted several research groups to study the disease and the associated herpesvirus, chelonid herpesvirus 5 (ChHV5). The present study detected and quantified ChHV5 in 153 fibropapilloma samples collected from green turtles Chelonia mydas on the Brazilian coast between 2009 and 2010 to characterize the relationship between viral load and tumor characteristics. Of the tumor samples collected, 73 and 87% were positive for ChHV5 in conventional PCR and real-time PCR, respectively, and viral loads ranged between 1 and 118.62 copies cell⁻¹. Thirty-three percent of turtles were mildly, 28% were moderately and 39% were severely affected with FP. Skin samples were used as negative control. High viral loads correlated positively with increasing FP severity in turtles sampled on the Brazilian coast and with samples from turtles found dead in the states of São Paulo and Bahia. Six viral variants were detected in tumor samples, 4 of which were similar to the Atlantic phylogenetic group. Two variants were similar to the western Atlantic/eastern Caribbean phylogenetic group. Co-infection in turtles with more than one variant was observed in the states of São Paulo and Bahia. PMID:25320033

  7. Mucoepidermoid carcinoma arising in Warthin’s tumor of the parotid gland: Clinicopathological characteristics and immunophenotypes

    PubMed Central

    Yu, Chunkai; Song, Zhigang; Xiao, Zhibo; Lin, Qiushi; Dong, Xiaoqun

    2016-01-01

    Mucoepidermoid carcinoma (MEC), an extremely rare tumor, arises from the epithelial component of preexisting parotid Warthin tumors (WT). Among the 309 cases of surgically resected WTs in Chinese PLA General Hospital and Beijing Shijitan Hospital of Capital Medical University, 5 cases (1.6%) fulfilled the criteria for MECs transformed from WTs. Clinicopathological characteristics of MECs was demonstrated in order to avoid misdiagnosis of this rare type of tumor. All the 5 patients, 3 males and 2 females, presented painless masses in the parotid gland. MECs were located inside or at the edge of WTs, with an obvious transitional zone between WT and MEC. Basal cells of WTs and epidermoid cells of MECs were strongly positive for cytokeratin CK5/6, CK34βE12, and P63; whereas negative for CK7, CK20, and CEA. Mucous cells of MECs were positive for CK7, CEA, as well as periodic acid-Schiff (PAS), whereas negative for CK5/6, CK34βE12, CK20, and P63. MECs patients were followed up for 25–69 months after surgery, presenting no evidence of recurrence or metastasis. Collectively, MECs arising from WT is very rare. The pathological diagnosis was based on histological morphology, especially the transitional zone between WT and MEC. PMID:27417276

  8. Fibropapillomatosis in green turtles Chelonia mydas in Brazil: characteristics of tumors and virus.

    PubMed

    Rodenbusch, C R; Baptistotte, C; Werneck, M R; Pires, T T; Melo, M T D; de Ataíde, M W; Testa, P; Alieve, M M; Canal, C W

    2014-10-16

    Fibropapillomatosis (FP) is a benign neoplasia that affects physiological functions of sea turtles and may lead to death. High prevalence of FP in sea turtle populations has prompted several research groups to study the disease and the associated herpesvirus, chelonid herpesvirus 5 (ChHV5). The present study detected and quantified ChHV5 in 153 fibropapilloma samples collected from green turtles Chelonia mydas on the Brazilian coast between 2009 and 2010 to characterize the relationship between viral load and tumor characteristics. Of the tumor samples collected, 73 and 87% were positive for ChHV5 in conventional PCR and real-time PCR, respectively, and viral loads ranged between 1 and 118.62 copies cell⁻¹. Thirty-three percent of turtles were mildly, 28% were moderately and 39% were severely affected with FP. Skin samples were used as negative control. High viral loads correlated positively with increasing FP severity in turtles sampled on the Brazilian coast and with samples from turtles found dead in the states of São Paulo and Bahia. Six viral variants were detected in tumor samples, 4 of which were similar to the Atlantic phylogenetic group. Two variants were similar to the western Atlantic/eastern Caribbean phylogenetic group. Co-infection in turtles with more than one variant was observed in the states of São Paulo and Bahia.

  9. [Aggressive fibromatoses].

    PubMed

    Döhler, J R; Hamelmann, H; Lasson, U

    1984-03-01

    Benign by nature, aggressive fibromatoses (desmoid fibromas) may represent as difficult therapeutic problems as malignant tumours. When subtotally resected they tend to recur. But spontaneous regression is possible. Expense and limits of their surgical treatment are discussed with reference to seven patients. In five cases primary affliction of bone was evident. There are three reports given in detail: In the first, malignant transformation may be due to radiation therapy and hemipelvectomy could not prevent recurrence. In the second, spontaneous regression of untreated pelvic affection may have occurred. In the third, several resections and amputation of the leg failed to cure congenital infantile fibromatosis.

  10. Clinical Characteristics and Outcomes for Solitary Fibrous Tumor (SFT): A Single Center Experience.

    PubMed

    DeVito, Nicholas; Henderson, Evita; Han, Gang; Reed, Damon; Bui, Marilyn M; Lavey, Robert; Robinson, Lary; Zager, Jonathan S; Gonzalez, Ricardo J; Sondak, Vernon K; Letson, G Douglas; Conley, Anthony

    2015-01-01

    Solitary fibrous tumor (SFT) is a mesenchymal neoplasm of fibrous origin. The 2013 WHO classification of soft tissue tumors defines malignant forms as hypercellular, mitotically active (>4 mitosis/10 high-power fields), with cytological atypia, tumor necrosis, and/or infiltrative margins. With an IRB-approved protocol, we investigated patient records and clinicopathologic data from our Sarcoma Database to describe the clinical characteristics of both benign and malignant SFT. All pathology specimens were reviewed by two pathologists. Descriptive statistics and univariate/multivariate survival analysis were performed. Patient records and Social Security Death Index were used to evaluate vital status. Of 82 patients, 47 (57%) were women and 73 (89%) were Caucasian. Median age was 62 years (range, 20 to 89). Thirty-two (39%) patients succumbed to the disease. Primary tumor site was lung/pleura in 28 (34%), abdomen/pelvis in 23 (28%), extremity in 13 (16%), and head/neck in 9 (11%) patients. Pathology was described as benign in 42 (51%) and malignant in 40 (49%) patients. Compared to benign SFT, malignant histology is associated with larger tumor size, higher mitotic counts, metastatic disease at diagnosis, and greater use of chemotherapy and radiation therapy. Gender, age, and tumor site were not significantly different between benign and malignant subtypes. By univariate analysis, only benign vs. malignant variant and complete resection positively impacted overall survival (P = 0.02 and P<0.0001, respectively). In the multivariable analysis of overall survival, receiving chemotherapy or not receiving surgery were two variables significantly associated with higher failure rate in overall survival: patients with chemotherapy vs. no chemotherapy (P = 0.003, HR = 4.55, with 95% CI: 1.68-12.34) and patients without surgery vs. with surgery (P = 0.005, HR = 25.49, with 95% CI: 2.62-247.57). Clear survival differences exist between benign and malignant SFT. While surgery

  11. Clinical Characteristics and Outcomes for Solitary Fibrous Tumor (SFT): A Single Center Experience.

    PubMed

    DeVito, Nicholas; Henderson, Evita; Han, Gang; Reed, Damon; Bui, Marilyn M; Lavey, Robert; Robinson, Lary; Zager, Jonathan S; Gonzalez, Ricardo J; Sondak, Vernon K; Letson, G Douglas; Conley, Anthony

    2015-01-01

    Solitary fibrous tumor (SFT) is a mesenchymal neoplasm of fibrous origin. The 2013 WHO classification of soft tissue tumors defines malignant forms as hypercellular, mitotically active (>4 mitosis/10 high-power fields), with cytological atypia, tumor necrosis, and/or infiltrative margins. With an IRB-approved protocol, we investigated patient records and clinicopathologic data from our Sarcoma Database to describe the clinical characteristics of both benign and malignant SFT. All pathology specimens were reviewed by two pathologists. Descriptive statistics and univariate/multivariate survival analysis were performed. Patient records and Social Security Death Index were used to evaluate vital status. Of 82 patients, 47 (57%) were women and 73 (89%) were Caucasian. Median age was 62 years (range, 20 to 89). Thirty-two (39%) patients succumbed to the disease. Primary tumor site was lung/pleura in 28 (34%), abdomen/pelvis in 23 (28%), extremity in 13 (16%), and head/neck in 9 (11%) patients. Pathology was described as benign in 42 (51%) and malignant in 40 (49%) patients. Compared to benign SFT, malignant histology is associated with larger tumor size, higher mitotic counts, metastatic disease at diagnosis, and greater use of chemotherapy and radiation therapy. Gender, age, and tumor site were not significantly different between benign and malignant subtypes. By univariate analysis, only benign vs. malignant variant and complete resection positively impacted overall survival (P = 0.02 and P<0.0001, respectively). In the multivariable analysis of overall survival, receiving chemotherapy or not receiving surgery were two variables significantly associated with higher failure rate in overall survival: patients with chemotherapy vs. no chemotherapy (P = 0.003, HR = 4.55, with 95% CI: 1.68-12.34) and patients without surgery vs. with surgery (P = 0.005, HR = 25.49, with 95% CI: 2.62-247.57). Clear survival differences exist between benign and malignant SFT. While surgery

  12. Rising thyroid cancer incidence in the United States by demographic and tumor characteristics, 1980–2005

    PubMed Central

    Enewold, Lindsey; Zhu, Kangmin; Ron, Elaine; Marrogi, Aizen J.; Stojadinovic, Alexander; Peoples, George E.; Devesa, Susan S.

    2009-01-01

    Thyroid cancer incidence has been rising in the United States, and this trend has often been attributed to heightened medical surveillance and use of improved diagnostics. Thyroid cancer incidence varies by sex and race/ethnicity, and these factors also influence access to and utilization of healthcare. We therefore examined thyroid cancer incidence rates by demographic and tumor characteristics, based on 48,403 thyroid cancer patients diagnosed during 1980–2005 from the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute. Rates varied by histologic type, sex, and race/ethnicity. Papillary carcinoma was the only histologic type for which incidence rates rose consistently among all racial/ethnic groups. Subsequent analyses focused on the 39,706 papillary thyroid cancers diagnosed during this period. Papillary carcinoma rates increased most rapidly among females. Between 1992–1995 and 2003–2005, they rose nearly 100% among White Non-Hispanics and Black females, but only 20–50% among White Hispanics, Asian/Pacific Islanders and Black males. Increases were most rapid for localized stage and small tumors; however, rates also rose for large tumors and tumors of regional and distant stage. Since 1992–1995, half the overall increase in papillary carcinoma rates was due to rising rates of very small (≤1.0 cm) cancers, 30% to cancers 1.1–2 cm, and 20% to cancers >2 cm. Among White females, the rate of increase for cancers >5 cm almost equaled that for the smallest cancers. Medical surveillance and more sensitive diagnostic procedures cannot completely explain the observed rises in papillary thyroid cancer rates. Thus, other possible explanations should be explored. PMID:19240234

  13. Molecular Characteristics of Malignant Ovarian Germ Cell Tumors and Comparison With Testicular Counterparts: Implications for Pathogenesis

    PubMed Central

    Kraggerud, Sigrid Marie; Hoei-Hansen, Christina E.; Alagaratnam, Sharmini; Skotheim, Rolf I.; Abeler, Vera M.

    2013-01-01

    This review focuses on the molecular characteristics and development of rare malignant ovarian germ cell tumors (mOGCTs). We provide an overview of the genomic aberrations assessed by ploidy, cytogenetic banding, and comparative genomic hybridization. We summarize and discuss the transcriptome profiles of mRNA and microRNA (miRNA), and biomarkers (DNA methylation, gene mutation, individual protein expression) for each mOGCT histological subtype. Parallels between the origin of mOGCT and their male counterpart testicular GCT (TGCT) are discussed from the perspective of germ cell development, endocrinological influences, and pathogenesis, as is the GCT origin in patients with disorders of sex development. Integrated molecular profiles of the 3 main histological subtypes, dysgerminoma (DG), yolk sac tumor (YST), and immature teratoma (IT), are presented. DGs show genomic aberrations comparable to TGCT. In contrast, the genome profiles of YST and IT are different both from each other and from DG/TGCT. Differences between DG and YST are underlined by their miRNA/mRNA expression patterns, suggesting preferential involvement of the WNT/β-catenin and TGF-β/bone morphogenetic protein signaling pathways among YSTs. Characteristic protein expression patterns are observed in DG, YST and IT. We propose that mOGCT develop through different developmental pathways, including one that is likely shared with TGCT and involves insufficient sexual differentiation of the germ cell niche. The molecular features of the mOGCTs underline their similarity to pluripotent precursor cells (primordial germ cells, PGCs) and other stem cells. This similarity combined with the process of ovary development, explain why mOGCTs present so early in life, and with greater histological complexity, than most somatic solid tumors. PMID:23575763

  14. Molecular characteristics of malignant ovarian germ cell tumors and comparison with testicular counterparts: implications for pathogenesis.

    PubMed

    Kraggerud, Sigrid Marie; Hoei-Hansen, Christina E; Alagaratnam, Sharmini; Skotheim, Rolf I; Abeler, Vera M; Rajpert-De Meyts, Ewa; Lothe, Ragnhild A

    2013-06-01

    This review focuses on the molecular characteristics and development of rare malignant ovarian germ cell tumors (mOGCTs). We provide an overview of the genomic aberrations assessed by ploidy, cytogenetic banding, and comparative genomic hybridization. We summarize and discuss the transcriptome profiles of mRNA and microRNA (miRNA), and biomarkers (DNA methylation, gene mutation, individual protein expression) for each mOGCT histological subtype. Parallels between the origin of mOGCT and their male counterpart testicular GCT (TGCT) are discussed from the perspective of germ cell development, endocrinological influences, and pathogenesis, as is the GCT origin in patients with disorders of sex development. Integrated molecular profiles of the 3 main histological subtypes, dysgerminoma (DG), yolk sac tumor (YST), and immature teratoma (IT), are presented. DGs show genomic aberrations comparable to TGCT. In contrast, the genome profiles of YST and IT are different both from each other and from DG/TGCT. Differences between DG and YST are underlined by their miRNA/mRNA expression patterns, suggesting preferential involvement of the WNT/β-catenin and TGF-β/bone morphogenetic protein signaling pathways among YSTs. Characteristic protein expression patterns are observed in DG, YST and IT. We propose that mOGCT develop through different developmental pathways, including one that is likely shared with TGCT and involves insufficient sexual differentiation of the germ cell niche. The molecular features of the mOGCTs underline their similarity to pluripotent precursor cells (primordial germ cells, PGCs) and other stem cells. This similarity combined with the process of ovary development, explain why mOGCTs present so early in life, and with greater histological complexity, than most somatic solid tumors. PMID:23575763

  15. Biomarkers to Distinguish Aggressive Cancers from Non-aggressive or Non-progressing Cancer — EDRN Public Portal

    Cancer.gov

    Distinguishing aggressive cancers from non-aggressive or non-progressing cancers is an issue of both clinical and public health importance particularly for those cancers with an available screening test. With respect to breast cancer, mammographic screening has been shown in randomized trials to reduce breast cancer mortality, but given the limitations of its sensitivity and specificity some breast cancers are missed by screening. These so called interval detected breast cancers diagnosed between regular screenings are known to have a more aggressive clinical profile. In addition, of those cancers detected by mammography some are indolent while others are more likely to recur despite treatment. The pilot study proposed herein is highly responsive to the EDRN supplement titled “Biomarkers to Distinguish Aggressive Cancers from Nonaggressive or Non-progressing Cancers” in that it addresses both of the research objectives related to these issues outlined in the notice for this supplement: Aim 1: To identify biomarkers in tumor tissue related to risk of interval detected vs. mammography screen detected breast cancer focusing on early stage invasive disease. We will compare gene expression profiles using the whole genome-cDNA-mediated Annealing, Selection, extension and Ligation (DASL) assay of 50 screen detected cancers to those of 50 interval detected cancers. Through this approach we will advance our understanding of the molecular characteristics of interval vs. screen detected breast cancers and discover novel biomarkers that distinguish between them. Aim 2: To identify biomarkers in tumor tissue related to risk of cancer recurrence among patients with screen detected early stage invasive breast cancer. Using the DASL assay we will compare gene expression profiles from screen detected early stage breast cancer that either recurred within five years or never recurred within five years. These two groups of patients will be matched on multiple factors including

  16. Anti-tumor effect of inflammatory neutrophils: characteristics of in vivo generation and in vitro tumor cell lysis.

    PubMed

    Lichtenstein, A; Kahle, J

    1985-01-15

    Inflammatory neutrophils elicited by intraperitoneal injection of Corynebacterium parvum, thioglycollate or proteose peptone were capable of lysing different murine and human tumor targets in a short-term chromium-release assay. A single-cell cytotoxicity assay, which evaluated effector-target cell interactions at the single-cell level, confirmed a PMN-mediated tumor-lytic effect. Optimal lysis was achieved by PMNs obtained 6 hr after injection of C. parvum and 16 hr after injection of thioglycollate. In vitro, loss of tumor cell membrane integrity occurred extremely rapidly following conjugation with inflammatory PMNs (beginning within 15 min of the binding step). By 45 min, the lytic event was completed. Addition of catalase or superoxide dismutase to the cytotoxicity assays prevented tumor lysis in a concentration-dependent fashion, indicating that hydrogen peroxide and superoxide, products of the PMN respiratory burst, are mediators of the lytic reaction. PMID:3917986

  17. Expression of Wnt and TGF-β pathway components and key adrenal transcription factors in adrenocortical tumors: association to carcinoma aggressiveness.

    PubMed

    Parviainen, Helka; Schrade, Anja; Kiiveri, Sanne; Prunskaite-Hyyryläinen, Renata; Haglund, Caj; Vainio, Seppo; Wilson, David B; Arola, Johanna; Heikinheimo, Markku

    2013-08-01

    Factors controlling benign and malignant adrenocortical tumorigenesis are largely unknown, but several mouse models suggest an important role for inhibin-alpha (INHA). To show that findings in the mouse are relevant to human tumors and clinical outcome, we investigated the expression of signaling proteins and transcription factors involved in the regulation of INHA in human tumor samples⋅ Thirty-one adrenocortical tumor samples, including 13 adrenocortical carcinomas (ACCs), were categorized according to Weiss score, hormonal profile, and patient survival data and analyzed using immunohistochemistry and RT-PCR. Expression of the TGF-β signaling mediator SMAD3 varied inversely with Weiss score, so that SMAD3 expression was lowest in the most malignant tumors. By contrast, SMAD2 expression was upregulated in most malignant tumors. Wnt pathway co-receptors LRP5 and LRP6 were predominantly expressed in benign adrenocortical tumors. In ACCs, expression of transcription factors GATA-6 and SF-1 correlated with that of their target gene INHA. Moreover, the diminished expression of GATA-6 and SF-1 in ACCs correlated with poor outcome. We conclude that the factors driving INHA expression are reduced in ACCs with poor outcome, implicating a role for INHA as a tumor suppressor in humans.

  18. Expression of Wnt and TGF-β pathway components and key adrenal transcription factors in adrenocortical tumors – association to carcinoma aggressiveness

    PubMed Central

    Parviainen, Helka; Schrade, Anja; Kiiveri, Sanne; Prunskaite-Hyyryläinen, Renata; Haglund, Caj; Vainio, Seppo; Wilson, David B.; Arola, Johanna; Heikinheimo, Markku

    2013-01-01

    Factors controlling benign and malignant adrenocortical tumorigenesis are largely unknown, but several mouse models suggest an important role for inhibin-alpha (INHA). To show that findings in the mouse are relevant to human tumors and clinical outcome, we investigated the expression of signaling proteins and transcription factors involved in the regulation of INHA in human tumor samples. Thirty-one adrenocortical tumor samples, including 13 adrenocortical carcinomas (ACCs), were categorized according to Weiss score, hormonal profile, and patient survival data and analyzed using immunohistochemistry and RT-PCR. Expression of the TGF-β signaling mediator SMAD3 varied inversely with Weiss score, so that SMAD3 expression was lowest in the most malignant tumors. By contrast, SMAD2 expression was upregulated in most malignant tumors. Wnt pathway co-receptors LRP5 and LRP6 were predominantly expressed in benign adrenocortical tumors. In ACCs, expression of transcription factors GATA-6 and SF-1 correlated with that of their target gene INHA. Moreover, the diminished expression of GATA-6 and SF-1 in ACCs correlated with poor outcome. We conclude that the factors driving INHA expression are reduced in ACCs with poor outcome, implicating a role for INHAas a tumor suppressor in humans. PMID:23866946

  19. Metastatic chondroblastoma. Report of a fatal case with a review of the literature on atypical, aggressive, and malignant chondroblastoma.

    PubMed

    Kyriakos, M; Land, V J; Penning, H L; Parker, S G

    1985-04-15

    A boy with metastatic and fatal chondroblastoma is presented. Unlike previously published examples of metastatic chondroblastoma, these metastases developed before any operative manipulation of the primary tumor. The histologic characteristics of the primary, metastatic, and locally recurrent tumors were those of a conventional chondroblastoma. A review of published cases of atypical, aggressive, and malignant chondroblastoma is presented with current follow-up information. Although some metastatic chondroblastomas may result from operative manipulation of the primary tumor and are clinically benign, other histologically benign chondroblastomas exist that are capable of pursuing a malignant course. The authors designate these as malignant chondroblastomas. No histologic criteria exist for the separation of these tumors.

  20. Metastatic chondroblastoma. Report of a fatal case with a review of the literature on atypical, aggressive, and malignant chondroblastoma.

    PubMed

    Kyriakos, M; Land, V J; Penning, H L; Parker, S G

    1985-04-15

    A boy with metastatic and fatal chondroblastoma is presented. Unlike previously published examples of metastatic chondroblastoma, these metastases developed before any operative manipulation of the primary tumor. The histologic characteristics of the primary, metastatic, and locally recurrent tumors were those of a conventional chondroblastoma. A review of published cases of atypical, aggressive, and malignant chondroblastoma is presented with current follow-up information. Although some metastatic chondroblastomas may result from operative manipulation of the primary tumor and are clinically benign, other histologically benign chondroblastomas exist that are capable of pursuing a malignant course. The authors designate these as malignant chondroblastomas. No histologic criteria exist for the separation of these tumors. PMID:3978565

  1. Aggressive rheumatoid arthritis registry in Italy. Characteristics of the early rheumatoid arthritis subtype among patients classified according to the ACR criteria.

    PubMed

    2003-01-01

    The Italian Society of Rheumatology in the year 2000 decided to sponsor the creation of a data base (Registry) of consecutive patients who fulfilled the diagnosis of rheumatoid arthritis (RA) according to the American College of Rheumatology (ACR) criteria. The registry is designed to collect data on the "aggressive" type of RA all over the country in order to determine the percentage of patients who satisfy the established criteria among incident cases of RA and to define the therapeutic approach according to the characteristics of the enrolled patients. Predefined criteria set up by eight recognized opinion leaders on the disease were used by all the centers to create the database. The GIARA registry (Gruppo Italiano Artrite Reumatoide Aggressiva) has now enrolled 706 patients who will be followed up for 24 months. They have been divided into two major subsets--patients with early (< 4 months' disease duration) and late (> 4 months) RA--with the aim of establishing whether differences in clinical, serological, radiographic and therapeutic (DMARDs: disease modifying antirheumatic drugs) parameters may distinguish the two subsets. The major conclusion of this preliminary analysis is that an overall tendency to undertreatment is discernable.

  2. Genetics Home Reference: desmoid tumor

    MedlinePlus

    ... in my area? Other Names for This Condition aggressive fibromatosis deep fibromatosis desmoid fibromatosis familial infiltrative fibromatosis ... catenin protein and somatic APC mutations in sporadic aggressive fibromatoses (desmoid tumors). Am J Pathol. 1997 Aug; ...

  3. Three-dimensional culture of a mixed mullerian tumor of the ovary: expression of in vivo characteristics

    NASA Technical Reports Server (NTRS)

    Goodwin, T. J.; Prewett, T. L.; Spaulding, G. F.; Becker, J. L.

    1997-01-01

    The Rotating-Wall Vessel (RWV) is a novel in vitro cell culture system used to successfully culture a cell line derived from a heterologous mixed mullerian tumor cell of the ovary. Although the original tumor was comprised of both epithelial and mesodermal components, long-term culture in conventional flasks established a cell line from this tumor with homogeneous epitheliallike growth characteristics (1). Cells from Passage 36 were seeded into a Rotating-Wall Vessel containing Cytodex-3 microcarrier beads. Scanning electron micrographs of tumor cells cultured for 32 d in the RWV showed the presence of heterogeneous cell populations organized into three-dimensional tissuelike architecture. Immunocytochemical analysis confirmed the cellular heterogeneity, as demonstrated by expression of both epithelial and mesenchymal antigens. Reverse transcription polymerase chain reaction amplification demonstrated the presence of mRNA for cellular oncogenes HER-2/neu, H-ras, K-ras, and tumor suppressor p53. Thus, there are two advantages to propagation of tissue in the RWV culture system:(a) tissue diversification representing populations present in the original tumor, and (b) the three-dimensional freedom to organize tissues morphologically akin to those observed in vivo. These data indicate that the RWV culture system is suitable for generating large quantities of ovarian tumor cells in vitro that are amenable to immunocytochemical, oncogenic, morphologic characteristics demonstrated in vivo.

  4. Histopathological characteristics of glutamine synthetase-positive hepatic tumor lesions in a mouse model of spontaneous metabolic syndrome (TSOD mouse)

    PubMed Central

    Takahashi, Tetsuyuki; Nishida, Takeshi; Baba, Hayato; Hatta, Hideki; Imura, Johji; Sutoh, Mitsuko; Toyohara, Syunji; Hokao, Ryoji; Watanabe, Syunsuke; Ogawa, Hirohisa; Uehara, Hisanori; Tsuneyama, Koichi

    2016-01-01

    We previously reported that Tsumura-Suzuki obese diabetic (TSOD) mice, a polygenic model of spontaneous type 2 diabetes, is a valuable model of hepatic carcinogenesis via non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). One of the characteristics of tumors in these mice is the diffuse expression of glutamine synthetase (GS), which is a diagnostic marker for hepatocellular carcinoma (HCC). In this study, we performed detailed histopathological examinations and found that GS expression was diffusely positive in >70% of the hepatic tumors from 15-month-old male TSOD mice. Translocation of β-catenin into nuclei with enhanced membranous expression also occurred in GS-positive tumors. Small lesions (<1 mm) in GS-positive cases exhibited dysplastic nodules, with severe nuclear atypia, whereas large lesions (>3 mm) bore the characteristics of human HCC, exhibiting nuclear and structural atypia with invasive growth. By contrast, the majority of GS-negative tumors were hepatocellular adenomas with advanced fatty change and low nuclear grade. In GS-negative tumors, loss of liver fatty acid-binding protein expression was observed. These results suggest that the histological characteristics of GS-positive hepatic tumors in TSOD mice resemble human HCC; thus, this model may be a useful tool in translational research targeting the NAFLD/NASH-HCC sequence. PMID:27446562

  5. High expression of TRF2, SOX10, and CD10 in circulating tumor microemboli detected in metastatic melanoma patients. A potential impact for the assessment of disease aggressiveness.

    PubMed

    Long, Elodie; Ilie, Marius; Bence, Coraline; Butori, Catherine; Selva, Eric; Lalvée, Salomé; Bonnetaud, Christelle; Poissonnet, Gilles; Lacour, Jean-Philippe; Bahadoran, Philippe; Brest, Patrick; Gilson, Eric; Ballotti, Robert; Hofman, Véronique; Hofman, Paul

    2016-06-01

    Circulating tumors cells (CTCs) can be detected in the blood of metastatic melanoma patients (MMPs) both as isolated circulating tumor cells (iCTCs) and circulating tumor microemboli (CTMs), but their clinical significance remains unknown. The aim of this work was to evaluate the prognostic impact in metastatic cutaneous melanoma of CTMs and iCTCs identified by a cytomorphological approach using the isolation by size of tumor cell (ISET) method. We characterized the phenotype of CTCs using anti-PS100, anti-SOX10, anti-CD10, and anti-TRF2 antibodies. 128 MMPs and 37 control healthy individuals with benign nevi were included in this study. Results were compared to the follow-up of patients. 109/128 (85%) MMPs showed CTCs, 44/128 (34%) with 2 to 6 CTMs and 65/128 (51%) with 4 to 9 iCTCs. PS100 expression was homogeneous in iCTCs and heterogeneous in CTMs. SOX10, CD10, and TRF2 were mainly expressed in CTMs. None of the control subjects demonstrated circulating malignant tumor cells. Overall survival was significantly decreased in patients with CTMs, independently of the therapeutic strategies. In conclusion, the presence of CTMs is an independent predictor of shorter survival from the time of diagnosis of MMPs.

  6. High expression of TRF2, SOX10, and CD10 in circulating tumor microemboli detected in metastatic melanoma patients. A potential impact for the assessment of disease aggressiveness.

    PubMed

    Long, Elodie; Ilie, Marius; Bence, Coraline; Butori, Catherine; Selva, Eric; Lalvée, Salomé; Bonnetaud, Christelle; Poissonnet, Gilles; Lacour, Jean-Philippe; Bahadoran, Philippe; Brest, Patrick; Gilson, Eric; Ballotti, Robert; Hofman, Véronique; Hofman, Paul

    2016-06-01

    Circulating tumors cells (CTCs) can be detected in the blood of metastatic melanoma patients (MMPs) both as isolated circulating tumor cells (iCTCs) and circulating tumor microemboli (CTMs), but their clinical significance remains unknown. The aim of this work was to evaluate the prognostic impact in metastatic cutaneous melanoma of CTMs and iCTCs identified by a cytomorphological approach using the isolation by size of tumor cell (ISET) method. We characterized the phenotype of CTCs using anti-PS100, anti-SOX10, anti-CD10, and anti-TRF2 antibodies. 128 MMPs and 37 control healthy individuals with benign nevi were included in this study. Results were compared to the follow-up of patients. 109/128 (85%) MMPs showed CTCs, 44/128 (34%) with 2 to 6 CTMs and 65/128 (51%) with 4 to 9 iCTCs. PS100 expression was homogeneous in iCTCs and heterogeneous in CTMs. SOX10, CD10, and TRF2 were mainly expressed in CTMs. None of the control subjects demonstrated circulating malignant tumor cells. Overall survival was significantly decreased in patients with CTMs, independently of the therapeutic strategies. In conclusion, the presence of CTMs is an independent predictor of shorter survival from the time of diagnosis of MMPs. PMID:26945789

  7. Chronic psychological stress and its impact on the development of aggressive breast cancer

    PubMed Central

    Cormanique, Thayse Fachin; de Almeida, Lirane Elize Defante Ferreto; Rech, Cynthia Alba; Rech, Daniel; Herrera, Ana Cristina da Silva do Amaral; Panis, Carolina

    2015-01-01

    Objective To investigate the clinicopathological findings of women diagnosed with breast cancer and study the impact of chronic psychological stress on the pathological characteristics of these tumors. Methods We investigated a cohort composed of women diagnosed with breast cancer and divided into two groups. One group was categorized as presenting with chronic psychological stress (by using the Self-Reporting Questionnaire − SRQ-20). Another group of women with breast cancer, but with no previous history of chronic psychological stress, comprised the Control Group. Clinical and pathological data were assessed. Results Women presenting with a history of chronic distress were significantly overweight when compared to the Control Group. Furthermore, it was observed that these stressed women also had a significant percentage of aggressive breast cancer subtype, the HER2 amplified tumor, which could be putatively associated with the loss of immunosurveillance. Conclusion Our findings suggested an interaction among chronic psychological stress, overweight, and the development of more aggressive breast tumors. PMID:26466057

  8. CONCEPT ANALYSIS: AGGRESSION

    PubMed Central

    Liu, Jianghong

    2006-01-01

    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 aggression are outlined. It is argued that a better understanding of aggression and the causal factors underlying it are essential for learning how to prevent negative aggression in the future. PMID:15371137

  9. [Characteristics of polyamine biosynthesis regulation and tumor growth rate in hormone-dependant grafted breast tumors of mice and rats].

    PubMed

    Orlovskiĭ, A A

    2007-01-01

    Effect of the inhibitors of polyamines biosynthesis on completely or partially hormone-dependant breast tumors (mouse Ca755 carcinoma and Walker W-256 carcinosarcoma) is essentially special: in contrary to hormone-dependant tumors, this effect may be not only breaking but stimulating as well. Change-over from one to another mode of reaction is conditioned, most probable, by hormonal status, which is determined by one or another estral cycle phase. Biochemical mechanisms of this change-over are closely connected with polyamines metabolism, namely the degree of polyamines (especially spermine) interconvertion and physiological reactivity level of the system controlling expression of ornithin-decarboxilase. At that, the first of these pathways is predominant for completely hormone-dependant Ca755 and the second one -for partially hormone-dependant W-256.

  10. Aggression in humans: what is its biological foundation?

    PubMed

    Albert, D J; Walsh, M L; Jonik, R H

    1993-01-01

    Although human aggression is frequently inferred to parallel aggression based on testosterone in nonprimate mammals, there is little concrete support for this position. High- and low-aggression individuals do not consistently differ in serum testosterone. Aggression does not change at puberty when testosterone levels increase. Aggression does not increase in hypogonadal males (or females) when exogenous testosterone is administered to support sexual activity. Similarly, there are no reports that aggression increases in hirsute females even though testosterone levels may rise to 200% above normal. Conversely, castration or antiandrogen administration to human males is not associated with a consistent decrease in aggression. Finally, changes in human aggression associated with neuropathology are not consistent with current knowledge of the neural basis of testosterone-dependent aggression. In contrast, human aggression does have a substantial number of features in common with defensive aggression seen in nonprimate mammals. It is present at all age levels, is displayed by both males and females, is directed at both males and females, and is not dependent on seasonal changes in hormone levels or experiential events such as sexual activity. As would be expected from current knowledge of the neural system controlling defensive aggression, aggression in humans increases with tumors in the medial hypothalamus and septal region, and with seizure activity in the amygdala. It decreases with lesions in the amygdala. The inference that human aggression has its roots in the defensive aggression of nonprimate mammals is in general agreement with evidence on the consistency of human aggressiveness over age, with similarities in male and female aggressiveness in laboratory studies, and with observations that some neurological disturbances contribute to criminal violence. This evidence suggests that human aggression has its biological roots in the defensive aggression of nonprimate

  11. Advances in understanding pituitary tumors

    PubMed Central

    Renner, Ulrich; Karl Stalla, Günter

    2014-01-01

    Pituitary tumors are common in the general population. Since neuroimaging techniques have improved, pituitary tumors are more often diagnosed incidentally. About 16.7% of the general population show changes in the pituitary gland. Predominantly, pituitary tumors are benign pituitary adenomas. Pituitary carcinomas or aggressive pituitary tumors are extremely rare. They might develop from benign adenomas. New genetic and epigenetic abnormalities help us to understand pituitary tumorigenesis and might lead to therapeutical targeting drugs in the future. Macroadenomas (>1 cm) can lead to visual field disturbances, compression of cranial nerves, hypopituitarism, and infiltration of the cavernous sinuses. The functional status of the pituitary tumor is important. About half to one third of all pituitary tumors are non-functioning pituitary adenomas. The other pituitary tumors show a specific pattern of hormone secretion. About 25% to 41% of all pituitary tumors are prolactinomas, acromegaly with production of growth hormone represents 10% to 15% of adenomas, Cushing's disease with production of adrenocorticotropic hormone accounts for 10%, and other hormonal characteristics are less common. Transsphenoidal resection and total adenomectomy are desirable. Radiosurgery has enriched the surgical treatment options. Surgical treatment is the intervention of choice except for prolactinomas, where pharmaceutical treatment is recommended. Pharmaceutical treatment consists of dopamine agonists such as cabergoline and somatostatin analogues that include octreotide and pasireotide; retinoic acid is of theoretical interest while peroxisome proliferator-activated receptor-gamma-ligands are not clinically useful. In acromegaly, pegvisomant is a further treatment option. Temozolomide should be considered in aggressive pituitary tumors. In general, pharmaceutical options developed recently have extended the repertoire of treatment possibilities of pituitary tumors. PMID:24592317

  12. Solitary fibrous tumor of the submandibular gland.

    PubMed

    Hofmann, Thiemo; Braun, Hannes; Köle, Wolfgang; Beham, Alfred

    2002-10-01

    Solitary fibrous tumors (SFT) are generally benign, well-circumscribed soft-tissue tumors of mesenchymal origin. CD34 antigen expression is characteristic for this tumor. A rare subgroup shows malignant histological patterns with aggressive behavior. The common site of occurrence is the pleura, but various other sites, including the head and neck, have been described. We present a 56-year-old, white, female patient with a solitary fibrous tumor developing in the right submandibular salivary gland. The tumor was surgically removed, and no recurrence or metastases have occurred during the 43 months of follow-up. All solitary fibrous tumors reported in the salivary glands were benign. However, new cases should be presented and followed up carefully to monitor their biological behavior.

  13. Symposium on Understanding Human Behavior and Experience -- Traits, States, and Situations -- Perspectives from Research on Aggression and Violent Behavior.

    ERIC Educational Resources Information Center

    Eron, L. D.

    This paper analyzes precursors of aggressive behavior and discusses the trait characteristics of aggression. The accumulating evidence for the heritability of aggression, the consistent physiological differences found between aggressive and non-aggressive subjects, the fact that males exhibit more aggression than females, and the belief that…

  14. Infratentorial low-grade oligoastrocytoma with aggressive clinical behavior in an adult: a case report with genetic characterization.

    PubMed

    Sano, Keisho; Toda, Masahiro; Sasaki, Hikaru; Kitamura, Yohei; Mikami, Shuji; Hirato, Junko; Inoue, Satoshi; Kawase, Takeshi; Yoshida, Kazunari

    2013-04-01

    Oligoastrocytoma preferentially arises in the cerebral hemisphere, and a cerebellar location is unusual. We report the case of a 35-year-old woman with an aggressive cerebellar tumor histopathologically diagnosed as oligoastrocytoma World Health Organization (WHO) grade II. After partial removal of the tumor, she underwent concomitant temozolomide (TMZ) therapy with local irradiation followed by additional TMZ monotherapy. However, her symptoms gradually worsened, and chronological magnetic resonance imaging showed remarkable tumor enlargement. In accordance with the aggressive clinical course, unfavorable genetic characteristics such as the gain of the entire chromosome 7, loss of 9p, absence of 1p/19q codeletion, absence of methylation of the O6-methylguanine-deoxyribonucleic acid methyltransferase promoter, and absence of the isocitrate dehydrogenase-1 mutation were observed. The present case illustrates that these molecular characteristics represent the biological features of gliomas more closely than the histopathological diagnosis and may also suggest that infratentorial gliomas arise through a distinct tumorigenic pathway from their supratentorial counterparts.

  15. Aggressive behavior problems.

    PubMed

    Beaver, B V

    1986-12-01

    Accurate diagnosis of the cause of aggression in horses is essential to determining the appropriate course of action. The affective forms of aggression include fear-induced, pain-induced, intermale, dominance, protective, maternal, learned, and redirected aggressions. Non-affective aggression includes play and sex-related forms. Irritable aggression and hypertestosteronism in mares are medical problems, whereas genetic factors, brain dysfunction, and self-mutilation are also concerns. PMID:3492250

  16. A Cross-Species Analysis in Pancreatic Neuroendocrine Tumors Reveals Molecular Subtypes with Distinctive Clinical, Metastatic, Developmental, and Metabolic Characteristics

    PubMed Central

    Sadanandam, Anguraj; Wullschleger, Stephan; Lyssiotis, Costas A.; Grötzinger, Carsten; Barbi, Stefano; Bersani, Samantha; Körner, Jan; Wafy, Ismael; Mafficini, Andrea; Lawlor, Rita T.; Simbolo, Michele; Asara, John M.; Bläker, Hendrik; Cantley, Lewis C.; Wiedenmann, Bertram; Scarpa, Aldo; Hanahan, Douglas

    2016-01-01

    Seeking to assess the representative and instructive value of an engineered mouse model of pancreatic neuroendocrine tumors (PanNET) for its cognate human cancer, we profiled and compared mRNA and miRNA transcriptomes of tumors from both. Mouse PanNET tumors could be classified into two distinctive subtypes, well-differentiated islet/insulinoma tumors (IT) and poorly differentiated tumors associated with liver metastases, dubbed metastasis-like primary (MLP). Human PanNETs were independently classified into these same two subtypes, along with a third, specific gene mutation–enriched subtype. The MLP subtypes in human and mouse were similar to liver metastases in terms of miRNA and mRNA transcriptome profiles and signature genes. The human/mouse MLP subtypes also similarly expressed genes known to regulate early pancreas development, whereas the IT subtypes expressed genes characteristic of mature islet cells, suggesting different tumorigenesis pathways. In addition, these subtypes exhibit distinct metabolic profiles marked by differential pyruvate metabolism, substantiating the significance of their separate identities. SIGNIFICANCE This study involves a comprehensive cross-species integrated analysis of multi-omics profiles and histology to stratify PanNETs into subtypes with distinctive characteristics. We provide support for the RIP1-TAG2 mouse model as representative of its cognate human cancer with prospects to better understand PanNET heterogeneity and consider future applications of personalized cancer therapy. PMID:26446169

  17. Treatment of Aggressive Prolactin-Secreting Pituitary Adenomas with Adjuvant Temozolomide Chemotherapy: A Review

    PubMed Central

    Cruz, Aurora S; Benkers, Tara; Rostad, Steven; Broyles, Frances Broyles; Yuen, Kevin; Mayberg, Marc

    2016-01-01

    Most prolactin-secreting pituitary adenomas demonstrate slow growth and are effectively managed with medical/surgical therapy. Rarely, these tumors can behave aggressively with rapid growth and invasion of local tissues, and are refractory to medical, surgical, or radio-surgical therapies. We report a case of a prolactin-secreting adenoma in a young woman, which became progressively aggressive and refractory to usual treatment modalities, but responded to treatment with the chemotherapeutic agent temozolomide. In addition, we review the literature for treatment of refractory adenomas with temozolomide. The clinical and pathologic characteristics of aggressive prolactin-secreting adenomas are reviewed, as well as their response to dopamine agonists, surgery, radiotherapy, and chemotherapy. PMID:27489751

  18. Treatment of Aggressive Prolactin-Secreting Pituitary Adenomas with Adjuvant Temozolomide Chemotherapy: A Review.

    PubMed

    Moisi, Marc; Cruz, Aurora S; Benkers, Tara; Rostad, Steven; Broyles, Frances Broyles; Yuen, Kevin; Mayberg, Marc

    2016-01-01

    Most prolactin-secreting pituitary adenomas demonstrate slow growth and are effectively managed with medical/surgical therapy. Rarely, these tumors can behave aggressively with rapid growth and invasion of local tissues, and are refractory to medical, surgical, or radio-surgical therapies. We report a case of a prolactin-secreting adenoma in a young woman, which became progressively aggressive and refractory to usual treatment modalities, but responded to treatment with the chemotherapeutic agent temozolomide. In addition, we review the literature for treatment of refractory adenomas with temozolomide. The clinical and pathologic characteristics of aggressive prolactin-secreting adenomas are reviewed, as well as their response to dopamine agonists, surgery, radiotherapy, and chemotherapy.

  19. Statistical assessment of bi-exponential diffusion weighted imaging signal characteristics induced by intravoxel incoherent motion in malignant breast tumors

    PubMed Central

    Wong, Oi Lei; Lo, Gladys G.; Chan, Helen H. L.; Wong, Ting Ting; Cheung, Polly S. Y.

    2016-01-01

    Background The purpose of this study is to statistically assess whether bi-exponential intravoxel incoherent motion (IVIM) model better characterizes diffusion weighted imaging (DWI) signal of malignant breast tumor than mono-exponential Gaussian diffusion model. Methods 3 T DWI data of 29 malignant breast tumors were retrospectively included. Linear least-square mono-exponential fitting and segmented least-square bi-exponential fitting were used for apparent diffusion coefficient (ADC) and IVIM parameter quantification, respectively. F-test and Akaike Information Criterion (AIC) were used to statistically assess the preference of mono-exponential and bi-exponential model using region-of-interests (ROI)-averaged and voxel-wise analysis. Results For ROI-averaged analysis, 15 tumors were significantly better fitted by bi-exponential function and 14 tumors exhibited mono-exponential behavior. The calculated ADC, D (true diffusion coefficient) and f (pseudo-diffusion fraction) showed no significant differences between mono-exponential and bi-exponential preferable tumors. Voxel-wise analysis revealed that 27 tumors contained more voxels exhibiting mono-exponential DWI decay while only 2 tumors presented more bi-exponential decay voxels. ADC was consistently and significantly larger than D for both ROI-averaged and voxel-wise analysis. Conclusions Although the presence of IVIM effect in malignant breast tumors could be suggested, statistical assessment shows that bi-exponential fitting does not necessarily better represent the DWI signal decay in breast cancer under clinically typical acquisition protocol and signal-to-noise ratio (SNR). Our study indicates the importance to statistically examine the breast cancer DWI signal characteristics in practice. PMID:27709078

  20. Histological and clinical characteristics of malignant giant cell tumor of bone.

    PubMed

    Gong, Lihua; Liu, Weifeng; Sun, Xiaoqi; Sajdik, Constantin; Tian, Xinxia; Niu, Xiaohui; Huang, Xiaoyuan

    2012-03-01

    Malignant giant cell tumors of bone (MGCTB) are rare, and the diagnosis can be difficult due to the occurrence of a variety of malignant tumors containing giant cells. To better understand its clinicopathological features, we have reviewed our experience with 17 cases of MGCTB. Five cases were primary malignant giant cell tumor of bone (PMGCTB), and 12 cases were giant cell tumors of bone initially diagnosed as benign but malignant in a recurrent lesion (secondary MGCTB, SMGCTB). The patients included six women and 11 men (age ranged from 17 to 52 years; mean, 30.5 years). The tumor arose in the femur (six cases), the tibia (seven cases), the humerus (three cases), and the fibula (one case). Microscopically, PMGCTB showed both conventional giant cell tumor and malignant sarcoma features. SMGCTB were initially diagnosed as conventional giant cell tumor of bone, the recurrent lesion showing malignant features. Histologically, the malignant components included osteosarcoma (11 cases), undifferentiated high-grade pleomorphic sarcoma (two cases), and fibrosarcoma (four cases). SMGCTB cases showed strong expression of p53. Follow-up information revealed that four patients died of lung metastasis, two patients are alive with lung metastases, and 11 patients are alive without tumor. MGCTB should be considered as a high-grade sarcoma. It must be distinguished from GCTB and other malignant tumors containing giant cells. p53 might play a role in the malignant transformation of GCTB. PMID:22350004

  1. Low Anger-Aggression and Anxiety-Withdrawal Characteristic to Preschoolers in Japanese Society Where "Hikikomori" Is Becoming a Major Social Problem.

    ERIC Educational Resources Information Center

    Masataka, Nobuo

    2002-01-01

    Evaluated social competence and problem behaviors of 200 Japanese preschoolers. Found anxiety-withdrawal, anger- aggression, and social competence factors as well as age and gender differences in emotional and behavioral problems and social competence. Found consistency with previous findings from U.S. and Canadian samples. (DLH)

  2. IDO is highly expressed in breast cancer and breast cancer-derived circulating microvesicles and associated to aggressive types of tumors by in silico analysis.

    PubMed

    Isla Larrain, M T; Rabassa, M E; Lacunza, E; Barbera, A; Cretón, A; Segal-Eiras, A; Croce, M V

    2014-07-01

    Indoleamine-2,3-dioxygenase (IDO) has been established as a normal mechanism of peripheral tolerance and immunosuppression. Besides, malignant tumors release microvesicles (MV) related with tumor dissemination. The aims of this study were to determine the expression of IDO in breast cancer and circulating microvesicles from breast cancer patients and to perform an in silico analysis to find genes co-expressed to IDO. One hundred and twenty-two tissue and serum breast samples (91 malignant, 21 benign, and 10 normal), and MCF7, MDA-MB-231, and T47D breast cancer cell lines were included. Standard immunohistochemistry (IHC), immunocytochemistry (ICC), Western blot (WB), and RT-PCR were employed. Microvesicle isolation from plasma samples was obtained by serial centrifugation and ultracentrifugation. By IHC, 60 % breast cancer, 43 % benign, and 20 % normal samples were positive. Significant differences were found among normal, benign, and malignant samples. Breast cancer stages I, II, and III expressed IDO in 42, 66, and 71 % of samples, respectively, while breast cancer cell lines also reacted; by WB, 9/25 microvesicles fractions showed bands at 42 kD. In silico analysis of IDO 1 gene expression in breast cancer showed its association with several genes related to immune response and apoptosis. Moreover, IDO and co-expressed genes were found predominately in basal and erbB2 subtypes. The cumulative data indicate a high expression of IDO in breast cancer which increased with higher stages. Furthermore, IDO was found in association with circulating breast cancer MV, while experimental and in silico gene expression revealed that IDO was mainly expressed in a triple-negative subgroup.

  3. [Meristematic characteristics of tumors initiated by Agrobacterium tumefaciens in pea plants].

    PubMed

    Vinogradova, A P; Lebedeva, M A; Lutova, L A

    2015-01-01

    It is known that two key groups of plant hormones--auxins and cytokinins--play an important role in plant tumor development. The formation of Agrobacterium-induced tumors results from the horizontal transfer of bacterial oncogenes involved in the biosynthesis of these hormones in the plant genome. The role of transcriptional factors in plant tumor development is poorly investigated. It can be assumed that tumor development associated with abnormal cell proliferation can be controlled by the same set of transcription factors that control normal cell proliferation and, in particular, transcription factors that regulate meristem activity. In the present study, we analyzed the histological organization and distribution of proliferating cells in tumors induced by Agrobacterium tumefaciens on pea hypocotyls. In addition, the expression of a set of meristem-specific genes with Agrobacterium tumefaciens-induced tumor development was analyzed. In general, our results indicate that meristematic structures are present in A. tumefaciens-induced tumors and that the development of such tumors is associated with increased expression of a key gene regulating the root apical meristem--the WOX5 gene.

  4. [Meristematic characteristics of tumors initiated by Agrobacterium tumefaciens in pea plants].

    PubMed

    Vinogradova, A P; Lebedeva, M A; Lutova, L A

    2015-01-01

    It is known that two key groups of plant hormones--auxins and cytokinins--play an important role in plant tumor development. The formation of Agrobacterium-induced tumors results from the horizontal transfer of bacterial oncogenes involved in the biosynthesis of these hormones in the plant genome. The role of transcriptional factors in plant tumor development is poorly investigated. It can be assumed that tumor development associated with abnormal cell proliferation can be controlled by the same set of transcription factors that control normal cell proliferation and, in particular, transcription factors that regulate meristem activity. In the present study, we analyzed the histological organization and distribution of proliferating cells in tumors induced by Agrobacterium tumefaciens on pea hypocotyls. In addition, the expression of a set of meristem-specific genes with Agrobacterium tumefaciens-induced tumor development was analyzed. In general, our results indicate that meristematic structures are present in A. tumefaciens-induced tumors and that the development of such tumors is associated with increased expression of a key gene regulating the root apical meristem--the WOX5 gene. PMID:25857193

  5. Morphology and growth characteristics of epithelial cells from classic Wilms' tumors.

    PubMed Central

    Hazen-Martin, D. J.; Garvin, A. J.; Gansler, T.; Tarnowski, B. I.; Sens, D. A.

    1993-01-01

    The ability to establish cell cultures representing the epithelial component of Wilms' tumor was determined for 18 cases of classic Wilms' tumors. From these 18 cases only two resulted in the culture of epithelial cells. Although the tumors from both cases were composed of a prominent epithelial component, other classic tumors not producing epithelial cell cultures also possessed appreciable epithelial components. Likewise, heterotransplants of these two primary tumors failed to give rise to epithelial cell cultures, although cultures of the blastemal element were produced. This suggests that Wilms' tumors may be prone to differentiate in different directions at varying times during tumor growth, possibly dependent on local tumor environment. Epithelial cells from these two classic cases were grown in culture in basal medium composed of a 1:1 mixture of Dulbecco's modified Eagle's medium and Ham's F-12 medium, supplemented with selenium, insulin, transferrin, hydrocortisone, tri-iodothyronine, and epidermal growth factor, on a collagen type I matrix with absorbed fetal calf serum proteins. One of the two cases also required the addition of bovine pituitary extract, ethanolamine, prostaglandin E1, and putrescine for optimum growth. Morphological analysis disclosed that the cultured cells were very similar to normal renal tubular cells in culture, except that the cells displayed little evidence for differentiated active ion transport and tended to grow in a multilayered arrangement. The culture of the epithelial cells from classic Wilms' tumors provides a model system for the study of tumor differentiation and progression. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 PMID:8384407

  6. Standardized orthotopic xenografts in zebrafish reveal glioma cell-line-specific characteristics and tumor cell heterogeneity

    PubMed Central

    Welker, Alessandra M.; Jaros, Brian D.; Puduvalli, Vinay K.; Imitola, Jaime; Kaur, Balveen; Beattie, Christine E.

    2016-01-01

    ABSTRACT Glioblastoma (GBM) is a deadly brain cancer, for which few effective drug treatments are available. Several studies have used zebrafish models to study GBM, but a standardized approach to modeling GBM in zebrafish was lacking to date, preventing comparison of data across studies. Here, we describe a new, standardized orthotopic xenotransplant model of GBM in zebrafish. Dose-response survival assays were used to define the optimal number of cells for tumor formation. Techniques to measure tumor burden and cell spread within the brain over real time were optimized using mouse neural stem cells as control transplants. Applying this standardized approach, we transplanted two patient-derived GBM cell lines, serum-grown adherent cells and neurospheres, into the midbrain region of embryonic zebrafish and analyzed transplanted larvae over time. Progressive brain tumor growth and premature larval death were observed using both cell lines; however, fewer transplanted neurosphere cells were needed for tumor growth and lethality. Tumors were heterogeneous, containing both cells expressing stem cell markers and cells expressing markers of differentiation. A small proportion of transplanted neurosphere cells expressed glial fibrillary acidic protein (GFAP) or vimentin, markers of more differentiated cells, but this number increased significantly during tumor growth, indicating that these cells undergo differentiation in vivo. By contrast, most serum-grown adherent cells expressed GFAP and vimentin at the earliest times examined post-transplant. Both cell types produced brain tumors that contained Sox2+ cells, indicative of tumor stem cells. Transplanted larvae were treated with currently used GBM therapeutics, temozolomide or bortezomib, and this resulted in a reduction in tumor volume in vivo and an increase in survival. The standardized model reported here facilitates robust and reproducible analysis of glioblastoma tumor cells in real time and provides a platform for

  7. LARG at chromosome 11q23 has functional characteristics of a tumor suppressor in human breast cancer

    SciTech Connect

    Ong, Danny C.T.; Rudduck, Christina; Chin, Koei; Kuo, Wen-Lin; Lie, Daniel K.H.; Chua, Constance L.M.; Wong, Chow Yin; Hong, Ga Sze; Gray, Joe; Lee, Ann S.G.

    2008-05-06

    Deletion of 11q23-q24 is frequent in a diverse variety of malignancies, including breast and colorectal carcinoma, implicating the presence of a tumor suppressor gene at that chromosomal region. We show here that LARG, from 11q23, has functional characteristics of a tumor suppressor. We examined a 6-Mb region on 11q23 by high-resolution deletion mapping, utilizing both loss of heterozygosity (LOH) analysis and microarray comparative genomic hybridization (CGH). LARG (also called ARHGEF12), identified from the analyzed region, was underexpressed in 34% of primary breast carcinomas and 80% of breast cancer cell lines including the MCF-7 line. Multiplex ligation-dependent probe amplification on 30 primary breast cancers and six breast cancer cell lines showed that LARG had the highest frequency of deletion compared to the BCSC-1 and TSLC1 genes, two known candidate tumor suppressor genes from 11q. In vitro analysis of breast cancer cell lines that underexpress LARG showed that LARG could be reactivated by trichostatin A, a histone deacetylase inhibitor, but not by 5-Aza-2{prime}-deoxycytidine, a demethylating agent. Bisulfite sequencing and quantitative high-throughput analysis of DNA methylation confirmed the lack of CpG island methylation in LARG in breast cancer. Restoration of LARG expression in MCF-7 cells by stable transfection resulted in reduced proliferation and colony formation, suggesting that LARG has functional characteristics of a tumor suppressor gene.

  8. Characteristics of Tumor Infiltrating Lymphocyte and Circulating Lymphocyte Repertoires in Pancreatic Cancer by the Sequencing of T Cell Receptors

    PubMed Central

    Bai, Xueli; Zhang, Qi; Wu, Song; Zhang, Xiaoyu; Wang, Mingbang; He, Fusheng; Wei, Tao; Yang, Jiaqi; Lou, Yu; Cai, Zhiming; Liang, Tingbo

    2015-01-01

    Pancreatic cancer has a poor prognosis and few effective treatments. The failure of treatment is partially due to the high heterogeneity of cancer cells within the tumor. T cells target and kill cancer cells by the specific recognition of cancer-associated antigens. In this study, T cells from primary tumor and blood of sixteen patients with pancreatic cancer were characterized by deep sequencing. T cells from blood of another eight healthy volunteers were also studied as controls. By analyzing the complementary determining region 3 (CDR3) gene sequence, we found no significant differences in the T cell receptor (TCR) repertoires between patients and healthy controls. Types and length of CDR3 were similar among groups. However, two clusters of patients were identified according to the degree of CDR3 overlap within tumor sample group. In addition, clonotypes with low frequencies were found in significantly higher numbers in primary pancreatic tumors compared to blood samples from patients and healthy controls. This study is the first to characterize the TCR repertoires of pancreatic cancers in both primary tumors and matched blood samples. The results imply that specific types of pancreatic cancer share potentially important immunological characteristics. PMID:26329277

  9. Peripheral primitive neuroectodermal tumor: Dynamic CT, MRI and clinicopathological characteristics - analysis of 36 cases and review of the literature

    PubMed Central

    Tan, Yan; Zhang, Hui; Ma, Guo-lin; Xiao, En-hua; Wang, Xiao-chun

    2014-01-01

    Background The peripheral primitive neuroectodermal tumor (pPNET) is a rare malignant tumor originating from neuroectoderm. The accurate diagnosis is essential for the treatment of pPNET. Methods we performed the largest cases of retrospective analysis thus far to review the unique computed tomography (CT), magnetic resonance imaging (MRI), and clinicopathological features of pPNET. The tumor location, morphological features, signal intensity, contrast enhancement characteristics, and involvement of local soft tissues of 36 pPNETs were assessed. Results Our results showed that there were more men (25/36) than women pPNETs patients. Unenhanced MRI (16 cases) showed that 14 cases were isointense and 2 cases were hypointense on T1WI. Nine cases were isointense and 7 were hyperintense on T2WI. Most pPNETs had heterogeneous signal intensity with small necrosis (CT: 31/36; MRI: 14/16) as well as heterogeneous enhancement (CT: 34/30; MRI: 15/16). The tumors usually had ill-defined borders and irregular shapes (CT: 30/36; MRI: 15/16). Pathologic exam showed small areas of necrosis in all tumors. Conclusions The diagnosis of pPNET should be suggested in young men when the imaging depicts a single large ill-defined solid mass with small area of necrosis, especially for those whose images show iso-intense on T1WI and T2WI and have heterogeneous enhancement. PMID:25587032

  10. Tumor Types

    MedlinePlus

    ... acoustic neuroma is also known as a schwannoma, vestibular schwannoma, or neurilemmoma. Characteristics Arises from cells that ... multiple CNS tumors, including neurofibromas, multiple meningiomas, bilateral vestibular schwannomas, optic nerve gliomas, and spinal cord tumors. ...

  11. The role of TMPRSS2:ERG in molecular stratification of PCa and its association with tumor aggressiveness: a study in Brazilian patients.

    PubMed

    Eguchi, Flávia C; Faria, Eliney F; Scapulatempo Neto, Cristovam; Longatto-Filho, Adhemar; Zanardo-Oliveira, Cleyton; Taboga, Sebastião R; Campos, Silvana G P

    2014-07-10

    Recurrent gene fusions between the genes TMPRSS2 and ERG have been described in prostate cancer (PCa) and are found in 27% to 79% of radical prostatectomy. This fusion transcription results in ERG overexpression, which can be detected by immunohistochemistry (IHC) and provide a potential diagnostic marker for PCa. Three tissue microarrays (TMAs) containing samples from 98 patients with PCa and one TMA of 27 samples from individuals without PCa were tested for ERG immunostaining, and the presence of TMPRSS2:ERG transcripts was confirmed by quantitative real time PCR (qRT-PCR). The results showed that 46.9% of tumors tested positive for ERG immunostaining, and this finding was consistent with the results of qRT-PCR testing (k = 0.694, p < 0.001). IHC had a specificity of 83.3% and a sensitivity of 81% in detecting TMPRSS2:ERG fusion. Patients with PSA < 4.0 ng/mL showed positive immunoreactivity for ERG (p = 0.031). Kaplan-Meier analysis suggested that ERG expression did not influence the time of biochemical recurrence. This study demonstrates that both IHC and qRT-PCR are useful tools in detecting TMPRSS2:ERG fusions. A correlation between ERG expression and clinical and pathological parameters was not found, but the frequency, specificity and recurrence of ERG in PCa suggests that it may be a potential adjunct diagnostic tool.

  12. Leptin increases prostate cancer aggressiveness.

    PubMed

    López Fontana, Constanza M; Maselli, María E; Pérez Elizalde, Rafael F; Di Milta Mónaco, Nicolás A; Uvilla Recupero, Ana L; López Laur, José D

    2011-12-01

    Recent studies indicate that adipose tissue and adipocytokines might affect the development of prostate cancer (PCa). Leptin would have a stimulating effect on prostate cancer cells by inducing promotion and progression, whereas adiponectin would have a protective effect. The aim of this study was to determine the relation between body composition, leptin, and adiponectin levels with the prevalence and aggressiveness of PCa in men of Mendoza, Argentina. Seventy volunteers between 50 and 80 years (35 healthy men as control group and 35 with PCa) were selected. The PCa group was subclassified according to the Gleason Score (GS). Digital rectal examination, transrectal ultrasound, and prostatic biopsy were performed; PSA, testosterone, leptin, and adiponectin levels were determined; and a nutritional interview including anthropometric measurements and a food frequency questionnaire was carried out. Statistical analysis was performed by Student t test, ANOVA I, and Bonferroni (p < 0.05). Body mass index and percentage of body fat mass were not statistically different between PCa and control groups. However, body fat mass was higher in subjects with more aggressive tumors (p = 0.032). No differences were observed regarding leptin levels between the groups. Nevertheless, leptin levels were higher in subjects with high GS (p < 0.001). Adiponectin levels showed no statistical differences regarding the presence and aggressiveness of the tumor (p = 0.131). Finally, consumption and nutrient intake did not differ in the studied groups. In conclusion, body composition and leptin are related to the PCa aggressiveness but not with its prevalence.

  13. Relational aggression in marriage.

    PubMed

    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.

  14. Establishing Chinese medicine characteristic tumor response evaluation system is the key to promote internationalization of Chinese medicine oncology.

    PubMed

    Li, Jie; Li, Lei; Liu, Rui; Lin, Hong-sheng

    2012-10-01

    The features and advantages of Chinese medicine (CM) in cancer comprehensive treatment have been in the spotlight of experts both at home and abroad. However, how to evaluate the effect of CM more objectively, scientifically and systematically is still the key problem of clinical trial, and also a limitation to the development and internationalization of CM oncology. The change of tumor response evaluation system in conventional medicine is gradually consistent with the features of CM clinical effect, such as they both focus on a combination of soft endpoints (i.e. quality of life, clinical benefit, etc.) and hard endpoints (i.e. tumor remission rate, time to progress, etc.). Although experts have proposed protocols of CM tumor response evaluation criteria and come to an agreement in general, divergences still exist in the importance, quantification and CM feature of the potential endpoints. Thus, establishing a CM characteristic and wildly accepted tumor response evaluation system is the key to promote internationalization of CM oncology, and also provides a more convenient and scientific platform for CM international cooperation and communication.

  15. The glucocorticoid/aggression relationship in animals and humans: an analysis sensitive to behavioral characteristics, glucocorticoid secretion patterns, and neural mechanisms.

    PubMed

    Haller, József

    2014-01-01

    Glucocorticoids control a wide array of biological processes from glucose homeostasis to neuronal function. The mechanisms mediating their effects are similarly varied and include rapid and transient nongenomic effects on calcium trafficking, various neurotransmitter receptors, and other membrane/cytoplasmic proteins, as well as slowly developing but durable genomic effects that are mediated by a large number of glucocorticoid-sensitive genes that are affected after variable lag-times. Given this complexity, we suggest that the aggression/glucocorticoid relationship cannot be reduced to the simple "stimulation/inhibition" question. Here, we review the effects of glucocorticoids on aggression by taking into account the complexities of glucocorticoid actions. Acute and chronic effects were differentiated because these are mediated by different mechanisms. The effects of chronic increases and decreases in glucocorticoid production were discussed separately, because the activation of mechanisms that are not normally activated and the loss of normal functions should not be confounded. Findings in healthy/normal subjects and those obtained in subjects that show abnormal forms of behavior or psychopathologies were also differentiated, because the effects of glucocorticoids are indirect, and largely depend on the properties of neurons they act upon, which are altered in subjects with psychopathologies. In addition, the conditions of glucocorticoid measurements were also thoroughly evaluated. Although the role of glucocorticoids in aggression is perceived as controversial by many investigators, a detailed analysis that is sensitive to glucocorticoid and behavioral measure as well as to the mediating mechanism suggests that this role is rather clear-cut; moreover, there is a marked similarity between animal and human findings.

  16. The distinctive molecular, pathological and clinical characteristics of BRAF-mutant colorectal tumors.

    PubMed

    Scartozzi, Mario; Giampieri, Riccardo; Aprile, Giuseppe; Iacono, Donatella; Santini, Daniele; dell'Aquila, Emanuela; Silvestris, Nicola; Gnoni, Antonio; Bonotto, Marta; Puzzoni, Marco; Demurtas, Laura; Cascinu, Stefano

    2015-01-01

    Several clinical series have demonstrated a notably low overall survival for colorectal cancer patients diagnosed with a BRAF-mutant tumor. A potentially interesting predictive role has also been suggested for BRAF-mutant colorectal cancer receiving anti-EGFR monoclonal antibodies. Although a global consensus exists in indicating BRAF as a prognostic factor with a possible predictive activity, the clinical use of BRAF mutational status in colorectal tumors is still controversial. This article reviews the current knowledge on the use and implications of BRAF mutational status in colorectal tumors, in order to define its present role in the clinical practice. Also suggested are possible treatment strategies in this prognostically challenging group of patients. Finally, a comprehensive outlook on future developments for specifically directed anti-BRAF therapy is illustrated.

  17. Imaging Tumor Hypoxia to Advance Radiation Oncology

    PubMed Central

    Lee, Chen-Ting; Boss, Mary-Keara

    2014-01-01

    Abstract Significance: Most solid tumors contain regions of low oxygenation or hypoxia. Tumor hypoxia has been associated with a poor clinical outcome and plays a critical role in tumor radioresistance. Recent Advances: Two main types of hypoxia exist in the tumor microenvironment: chronic and cycling hypoxia. Chronic hypoxia results from the limited diffusion distance of oxygen, and cycling hypoxia primarily results from the variation in microvessel red blood cell flux and temporary disturbances in perfusion. Chronic hypoxia may cause either tumor progression or regressive effects depending on the tumor model. However, there is a general trend toward the development of a more aggressive phenotype after cycling hypoxia. With advanced hypoxia imaging techniques, spatiotemporal characteristics of tumor hypoxia and the changes to the tumor microenvironment can be analyzed. Critical Issues: In this review, we focus on the biological and clinical consequences of chronic and cycling hypoxia on radiation treatment. We also discuss the advanced non-invasive imaging techniques that have been developed to detect and monitor tumor hypoxia in preclinical and clinical studies. Future Directions: A better understanding of the mechanisms of tumor hypoxia with non-invasive imaging will provide a basis for improved radiation therapeutic practices. Antioxid. Redox Signal. 21, 313–337. PMID:24329000

  18. [Enophthalmos in an orbital tumor].

    PubMed

    Szabo, Bianca; Szabo, I; Nicula, Cristina; Popescu, Livia Adriana

    2013-01-01

    Enophtalmus is an unusual sign of the orbital tumors often represented by proptosis. One patient with enophtalmus and intraorbital tumor and aplasy is presented. The treatment of choice of orbital tumor is complete surgical excision and careful follow-up. Considering the more aggressive course followed by recurrent tumor, correct diagnosis and management is essential.

  19. Alcohol and risk of breast cancer in postmenopausal women: an analysis of etiological heterogeneity by multiple tumor characteristics.

    PubMed

    Falk, Roni T; Maas, Paige; Schairer, Catherine; Chatterjee, Nilanjan; Mabie, Jerome E; Cunningham, Christopher; Buys, Saundra S; Isaacs, Claudine; Ziegler, Regina G

    2014-10-01

    Alcohol consumption is an established risk factor for breast cancer. Whether associations vary by specific tumor characteristics independent of other characteristics is unclear. We evaluated the association between alcohol consumption and breast cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort (54,562 women aged 55-74 years recruited at 10 US screening centers between 1993 and 2001; median follow-up, 8.9 years; 1,905 invasive breast cancer cases). Hazard ratios and 95% confidence intervals for subtypes defined by histological type and estrogen receptor (ER)/progesterone receptor (PR) status were calculated with standard Cox models. A novel 2-stage Cox model assessed heterogeneity in risk for individual tumor characteristics while adjusting for others. Significant trends across categories of alcohol consumption were observed, with hazard ratios for those consuming 7 or more drinks per week versus never drinkers as follows: for estrogen receptor-positive (ER+) cancer, 1.48 (95% confidence interval (CI): 1.19, 1.83); for progesterone receptor-positive (PR+) cancer, 1.64 (95% CI: 1.31, 2.06); for ER+/PR+ cancer, 1.63 (95% CI: 1.30, 2.05); and for mixed ductal/lobular cancer, 2.51 (95% CI: 1.20, 5.24). For ER+ and PR+ cancers, trends were significant for ductal and mixed ductal/lobular types. PR status explained the positive association with ER status (for ER status, Pheterogeneity=0.70 after adjustment for PR status). Alcohol consumption was not associated with all breast cancer subtypes. Future work should emphasize large collaborative studies, precise definition of subtypes, and adjustment for correlated tumor characteristics.

  20. Genomic instability at the 13q31 locus and somatic mtDNA mutation in the D-loop site correlate with tumor aggressiveness in sporadic Brazilian breast cancer cases

    PubMed Central

    dos Santos, Gilson Costa; de Souza Góes, Andréa Carla; de Vitto, Humberto; Moreira, Carla Cristina; Avvad, Elizabeth; Rumjanek, Franklin David; de Moura Gallo, Claudia Vitoria

    2012-01-01

    OBJECTIVE: Genomic instability is a hallmark of malignant tissues. In this work, we aimed to characterize nuclear and mitochondrial instabilities by determining short tandem repeats and somatic mitochondrial mutations, respectively, in a cohort of Brazilian sporadic breast cancer cases. Furthermore, we performed an association analysis of the molecular findings and the clinical pathological data. METHODS: We analyzed 64 matched pairs of breast cancer and adjacent non-cancerous breast samples by genotyping 13 nuclear short tandem repeat loci (namely, D2S123, TPOX, D3S1358, D3S1611, FGA, D7S820, TH01, D13S317, D13S790, D16S539, D17S796, intron 12 BRCA1 and intron 1 TP53) that were amplified with the fluorescent AmpFlSTR Identifiler Genotyping system (Applied Biosystems, USA) and by silver nitrate staining following 6% denaturing polyacrylamide gel electrophoresis. Somatic mtDNA mutations in the D-loop site were assessed with direct sequencing of the hypervariable HVI and HVII mitochondrial regions. RESULTS: Half of the cancer tissues presented some nuclear instability. Interestingly, the D13S790 locus was the most frequently affected (36%), while the D2S123 locus presented no alterations. Forty-two percent of the cases showed somatic mitochondrial mutations, the majority at region 303-315 poly-C. We identified associations between Elston grade III, instabilities at 13q31 region (p = 0.0264) and mtDNA mutations (p = 0.0041). Furthermore, instabilities at 13q31 region were also associated with TP53 mutations in the invasive ductal carcinoma cases (p = 0.0207). CONCLUSION: Instabilities at 13q31 region and the presence of somatic mtDNA mutations in a D-loop site correlated with tumor aggressiveness. PMID:23070345

  1. Characteristics of oncolytic vesicular stomatitis virus displaying tumor-targeting ligands.

    PubMed

    Ammayappan, Arun; Peng, Kah-Whye; Russell, Stephen J

    2013-12-01

    We sought proof of principle that tumor-targeting ligands can be displayed on the surface of vesicular stomatitis virus (VSV) by engineering its glycoprotein. Here, we successfully rescued VSVs displaying tumor vasculature-targeting ligands. By using a rational approach, we investigated various feasible insertion sites on the G protein of VSV (VSV-G) for display of tumor vasculature-targeting ligands, cyclic RGD (cRGD) and echistatin. We found seven sites on VSV-G that tolerated insertion of the 9-residue cRGD peptide, two of which could tolerate insertion of the 49-amino acid echistatin domain. All of the ligand-displaying viruses replicated as well as the parental virus. In vitro studies demonstrated that the VSV-echistatin viruses specifically bound to targeted integrins. Since the low-density lipoprotein receptor (LDLR) was recently identified as a major receptor for VSV, we investigated the entry of ligand-displaying viruses after masking LDLR. The experiment showed that the modified viruses can enter the cell independently of LDLR, whereas entry of unmodified virus is significantly blocked by a specific monoclonal antibody against LDLR. Both parental and ligand-displaying viruses displayed equal oncolytic efficacies in a syngeneic mouse myeloma model. We further demonstrated that single-chain antibody fragments against tumor-specific antigens can be inserted at the N terminus of the G protein and that corresponding replication-competent VSVs can be rescued efficiently. Overall, we demonstrated that functional tumor-targeting ligands can be displayed on replication-competent VSVs without perturbing viral growth and oncolytic efficacy. This study provides a rational foundation for the future development of fully retargeted oncolytic VSVs.

  2. Mixed Adeno-neuroendocrine Carcinoma: An Aggressive Clinical Entity

    PubMed Central

    Brathwaite, Shayna; Rock, Jonathan; Yearsley, Martha M.; Bekaii-Saab, Tanios; Wei, Lai; Frankel, Wendy L.; Hays, John; Wu, Christina; Abdel-Misih, Sherif

    2016-01-01

    Background Mixed adeno-neuroendocrine carcinoma (MANEC) is a rare pathologic diagnosis recently defined by the World Health Organization in 2010. Due to poor understanding of MANEC as a clinical entity, there is significant variation in the management of these patients. The purpose of our study was to characterize MANEC to develop evidence-based treatment strategies. Methods The Ohio State University patient database was queried for the diagnosis of MANEC and 46 patients were identified. For comparison, the database also was queried for goblet cell carcinoid (GCC) of the appendix, signet ring cell carcinoma, and carcinoid/neuroendocrine tumor of the appendix. Charts were then retrospectively reviewed for clinicopathologic characteristics, patient treatment, and survival data. Results The mean age of diagnosis of MANEC was 54 years. Eighty-seven percent of MANEC arose from the appendix, with 28 % of patients undergoing appendectomy and 35 % undergoing right hemicolectomy as their index operation. Immunohistochemical staining was positive for chromogranin (82 %), synaptophysin (97 %), and CD56 (67 %). Sixty-seven percent of patients presented with stage IV disease and 41 % had nodal metastases. Overall survival was 4.1 years, which was statistically significantly different (p ≤ 0.05) compared with carcinoid tumors (13.4 years), GCC (15.4 years), and signet ring carcinoma (2.2 years). Conclusions MANEC is a more aggressive clinical entity than both GCC of the appendix and carcinoid/neuroendocrine tumors of the appendix. Based on these findings, we recommend patients with MANEC tumors undergo aggressive multidisciplinary cancer management and close surveillance. PMID:26965701

  3. Methylated APC and GSTP1 genes in serum DNA correlate with the presence of circulating blood tumor cells and are associated with a more aggressive and advanced breast cancer disease

    PubMed Central

    2010-01-01

    significantly correlated with positive Her2/neu status (p = 0.003). Elevated serum CA15.3 was strongly correlated with methylated APC and CTC detection (both p = 0.000). Methylated ESR1 failed to exhibit significant correlations with any of the above mentioned parameters. The presence of CTC in peripheral blood was significantly associated with methylated APC (p = 0.012) and methylated GSTP1 (p = 0.001). Conclusion The detection of methylated APC and GSTP1 DNA in serum correlated with the presence of CTC in the blood of breast cancer patients. Both methylated DNA and CTC correlated with a more aggressive tumor biology and advanced disease. PMID:20696638

  4. Familial pituitary tumors.

    PubMed

    Alband, Neda; Korbonits, Márta

    2014-01-01

    Pituitary adenomas are benign intracranial neoplasms that present a major clinical concern due to hormone overproduction and/or tumor mass effects. The majority of pituitary adenomas occur sporadically; however, familial cases are increasingly being recognized, such as multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC), and familial isolated pituitary adenoma (FIPA). Familial pituitary tumors appear to differ from their sporadic counterparts both in their genetic basis and in clinical characteristics. Evidence suggests that, especially in MEN1 and FIPA, tumors are more aggressive and affect patients at a younger age, therefore justifying the importance of early diagnosis, while in Carney complex pituitary hyperplasia is common. The genetic alterations responsible for the formation of familial pituitary syndromes include the MEN1 gene, responsible for about 80% of MEN1 cases, the regulatory subunit of the protein kinase A, PRKAR1A, responsible for about 70% of Carney complex cases, and AIP, the gene coding the aryl hydrocarbon receptor interacting protein, responsible for about 20% of FIPA cases. Rarely other genes have also been found responsible for familial pituitary adenoma cases. McCune-Albright syndrome (MAS) also has a genetic origin due to mosaic mutations in the G protein-coupled α subunit coded by the GNAS1 gene. In this chapter, we summarize the genetic and clinical characteristics of these familial pituitary syndromes and MAS. PMID:25248598

  5. Genetic associations of short- and long-term aggressiveness identified by skin lesion with growth, feed efficiency, and carcass characteristics in growing pigs.

    PubMed

    Desire, S; Turner, S P; D'Eath, R B; Doeschl-Wilson, A B; Lewis, C R G; Roehe, R

    2015-07-01

    The objective of this study was to investigate the genetic relationships between skin lesion traits in group housed growing pigs as a measure of short- (in a newly mixed group) and long- (in a socially stable group) term aggression and commonly used commercial performance measures: growth, feed intake, feed efficiency, and carcass traits. Data on 2,413 growing pigs (138 groups) were available. Pigs were mixed into new social groups of 18 animals, and skin lesions were counted 24 h (SL24h) and 5 wk (SL5wk) postmixing. The animal model was used to estimate genetic parameters for skin lesion traits, test daily gain, lifetime daily gain, daily feed intake, feed efficiency (calculated as test daily gain divided by daily feed intake), loin depth, back fat, and HCW. Skin lesions had a heritable component, ranging from 0.08 for anterior SL24h to 0.22 for central SL5wk and would, therefore, be suitable as a method of phenotyping aggression for selection purposes. Significant positive genetic correlations were found between SL24h and SL5wk (0.46 to 0.81). Positive genetic correlations were also found between SL24h (central and posterior body regions) or SL5wk (all body regions) and the production traits lifetime daily gain, test daily gain, and HCW (0.29 to 0.54). Central SL24h, anterior SL5wk, and posterior SL5wk were found to correlate positively with feed efficiency (0.39 to 0.50), suggesting that pigs with more lesions convert feed more efficiently. Where significant, the magnitude of phenotypic correlations was low but positive (0.07 to 0.10). These results suggest that, genetically, animals that receive many lesions show improved performance compared to those with few lesions, except for anterior SL24h, which had previously been shown to be genetically positively correlated with the initiation of nonreciprocal attacks. It may, therefore, be possible, via selection against anterior skin lesions at mixing, to reduce this form of 1-sided aggression without adversely

  6. Discussion based on numerical and experimental studies on heating characteristics of an RF rectangular resonant cavity applicator for hyperthermia targeting deep-seated tumors.

    PubMed

    Tange, Yutaka; Kanai, Yasushi; Saitoh, Yoshiaki

    2007-01-01

    The heating characteristics of an RF rectangular cavity applicator for hyperthermic treatment that targets deep-seated tumors were investigated numerically and experimentally. In the numerical study, Maxwell's equations and heat transfer equations were solved for a dielectric phantom with and without blood flow. Conductive caps attached to the dielectric phantom to shield the non-tumor regions. The experimental study showed the validity and possibility of heating deep-seated tumors. Thus, the rectangular resonant cavity applicator with an L-type antenna can heat deep-seated tumors.

  7. Computed tomographic characteristics of multilobular tumor of bone involving the cranium in 7 dogs and zygomatic arch in 2 dogs.

    PubMed

    Hathcock, J T; Newton, J C

    2000-01-01

    Computed tomography (CT) images of nine dogs with a multilobular tumor of bone of the head were reviewed. The CT characteristics of the neoplasms involving the calvarium (n = 7) were rounded, well defined with a fine granular, nonhomogeneous bone opacity usually in the occipital region. Cranial vault invasion (5 of 7) was commonly found with a significant portion of the mass within the vault. The neoplasms involving the zygomatic arch (n = 2) were also generally rounded and well defined but with a more coarse granular appearance. The common CT findings were best seen when the images were viewed in a bone window.

  8. Punishment of elicited aggression.

    PubMed

    Azrin, N H

    1970-07-01

    Aversive shocks are known to produce aggression when the shocks are not dependent on behavior and to suppress behavior when the shocks are arranged as a dependent punisher. These two processes were studied by presenting non-dependent shock to monkeys at regular intervals, thereby producing biting attacks on a pneumatic tube. Immediate shock punishment was stimultaneously delivered for each biting attack. The attacks were found to decrease as a function of increasing punishment intensity. These results show that aggression is eliminated by direct punishment of the aggression even when the stimulus that is used as a punisher otherwise causes the aggression. PMID:4988590

  9. Tryptophan content for monitoring breast cancer cell aggressiveness by native fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Zhang, Lin; Pu, Yang; Xue, Jianpeng; Pratavieira, Sebastião.; Xu, Baogang; Achilefu, Samuel; Alfano, R. R.

    2014-03-01

    This study shows tryptophan as the key native marker in cells to determine the level of aggressive cancer in breast cell lines using native fluorescence spectroscopy. An algorithm based on the ratio of tryptophan fluorescence intensity at 340 nm to intensity at 460 nm is associated with aggressiveness of the cancer cells. The higher the ratio is, the more aggressive the tumor towards metastasis.

  10. Early-Stage Breast Cancer in the Octogenarian: Tumor Characteristics, Treatment Choices, and Clinical Outcomes

    PubMed Central

    Mamtani, Anita; Gonzalez, Julie J.; Neo, Dayna; Slanetz, Priscilla J.; Houlihan, Mary Jane; Herold, Christina I.; Recht, Abram; Hacker, Michele R.; Sharma, Ranjna

    2016-01-01

    Background Nodal staging with sentinel node biopsy (SLNB), post-lumpectomy radiotherapy (RT), and endocrine therapy (ET) for estrogen receptor-positive (ER+) tumors is valuable in the treatment of early-stage (stages 1 or 2) breast cancer but used less often for elderly women. Methods This retrospective study investigated women referred for surgical evaluation of biopsy-proven primary early-stage invasive breast cancer from January 2001 to December 2010. Clinicopathologic features, treatment course, and outcomes for women ages 80–89 years and 50–59 years were compared. Results The study identified 178 eligible women ages 80–89 years and 169 women ages 50–59 years. The elderly women more often had grade 1 or 2 disease (p = 0.003) and ER+ tumors (p = 0.007) and less frequently had undergone adjuvant therapies (all p ≤ 0.001). Lumpectomy was performed more commonly for the elderly (92 vs. 83 %, p = 0.02), and axillary surgery was less commonly performed (46 vs. 96 %; p < 0.001). Fewer elderly women had undergone post-lumpectomy RT (42 vs. 89 %; p < 0.001) and ET for ER+ tumors (72 vs. 95 %; p < 0.001). During the median follow-up period of 56 months for the 80- to 89-year old group and 98 months for the 50- to 59-year-old group, death from breast cancer was similar (4 vs. 5 %; p = 0.5). The two groups respectively experienced 7 versus 6 locoregional recurrences and 11 versus 13 distant recurrences. Conclusions The octogenarians had disease survivorship similar to that of the younger women despite less frequent use of adjuvant therapies, likely reflecting lower-risk disease features. Whether increased use of axillary surgery, post-lumpectomy RT, and/or ET for ER+ tumors would further improve outcomes is an important area for further study, but treatment should not be deferred solely on the basis of age. PMID:27364507

  11. The Clinical Significance and Molecular Features of the Spatial Tumor Shapes in Breast Cancers

    PubMed Central

    Jeong, Seongmun; Lee, Minju; Moon, HyunHye; Kim, Jongjin; Yoo, Tae-Kyung; Lee, Han-Byoel; Kim, Jisun; Noh, Dong-Young; Han, Wonshik

    2015-01-01

    Each breast cancer has its unique spatial shape, but the clinical importance and the underlying mechanism for the three-dimensional tumor shapes are mostly unknown. We collected the data on the three-dimensional tumor size and tumor volume data of invasive breast cancers from 2,250 patients who underwent surgery between Jan 2000 and Jul 2007. The degree of tumor eccentricity was estimated by using the difference between the spheroid tumor volume and ellipsoid tumor volume (spheroid-ellipsoid discrepancy, SED). In 41 patients, transcriptome and exome sequencing data obtained. Estimation of more accurate tumor burden by calculating ellipsoid tumor volumes did not improve the outcome prediction when compared to the traditional longest diameter measurement. However, the spatial tumor eccentricity, which was measured by SED, showed significant variation between the molecular subtypes of breast cancer. Additionally, the degree of tumor eccentricity was associated with well-known prognostic factors of breast cancer such as tumor size and lymph node metastasis. Transcriptome data from 41 patients showed significant association between MMP13 and spatial tumor shapes. Network analysis and analysis of TCGA gene expression data suggest that MMP13 is regulated by ERBB2 and S100A7A. The present study validates the usefulness of the current tumor size method in determining tumor stages. Furthermore, we show that the tumors with high eccentricity are more likely to have aggressive tumor characteristics. Genes involved in the extracellular matrix remodeling can be candidate regulators of the spatial tumor shapes in breast cancer. PMID:26669540

  12. Epidemiologic and molecular characteristics of borderline and malignant epithelial ovarian tumors

    NASA Astrophysics Data System (ADS)

    Bastos, Eugenia Maria Chaves De Moraes

    Data from the Cancer and Steroid Hormone Study, a multicenter, population-based, case-control study were used to identify risk factors for epithelial ovarian cancer according to tumor behavior, histologic types, as well as p53 expression. Cases were women between 20 to 54 years old diagnosed with epithelial ovarian cancer from 1980 to 1982. Controls were women selected by random digit dialing. Tumor samples were analyzed for p53 overexpression using immunohistochemistry. Case-case and case-control conditional logistic regression models matched on age and diagnosing centers were used to calculate odds ratios (OR's) and 95% confidence intervals (CI's) for borderline, malignant, mucinous, and nonmucinous tumors, and p53 positive and p53 negative cases. The OR's for high number of lifetime ovulatory cycles (376-533 compared with less than 234) were 3.1 (95% CI 1.6-6.1) for malignant and 1.4 (95% CI 0.5-3.7) for borderline cases. The high number of ovulatory cycles was also a strong risk factor among nonmucinous cases. OR's for current and recent ex-smokers compared with never smokers were 2.8 (95% CI 1.7-4.8) for mucinous and 0.9 (95% CI 0.7-1.1) for nonmucinous types. Infertility showed a positive association with borderline ovarian cancer. Family history of ovarian or breast cancer was positively associated with malignant and nonmucinous cases. Parity had an inverse association with malignant ovarian cancer cases. When cases were subdivided by p53 results, the OR for tobacco smoking and p53 positive ovarian cancer was elevated for mucinous (OR = 3.9; 95% CI 0.8-18) at localized stage. Alcohol use showed a positive association with p53 positive malignant cases at advanced stage (OR = 2.0; 95% CI 1.2-3.2) and with p53 positive nonmucinous cases at advanced stage (OR = 2.1; 95% CI 1.2-3.4). A positive association between high number of ovulatory cycles and p53 positive malignant cases was observed in cases with localized stage (OR = 6.6; 95% CI 1.0-45) and advanced

  13. An Individual Patient Data Meta-Analysis on Characteristics and Outcome of Patients with Papillary Glioneuronal Tumor, Rosette Glioneuronal Tumor with Neuropil-Like Islands and Rosette Forming Glioneuronal Tumor of the Fourth Ventricle

    PubMed Central

    Hagel, Christian; Zwiener, Isabella; Seidel, Clemens; Kortmann, Rolf-Dieter; Müller, Klaus

    2014-01-01

    Background and Purpose In 2007, the WHO classification of brain tumors was extended by three new entities of glioneuronal tumors: papillary glioneuronal tumor (PGNT), rosette-forming glioneuronal tumor of the fourth ventricle (RGNT) and glioneuronal tumor with neuropil-like islands (GNTNI). Focusing on clinical characteristics and outcome, the authors performed a comprehensive individual patient data (IPD) meta-analysis of the cases reported in literature until December 2012. Methods PubMed, Embase and Web of Science were searched for peer-reviewed articles reporting on PGNT, RGNT, and GNTNI using predefined keywords. Results 95 publications reported on 182 patients (PGNT, 71; GNTNI, 26; RGNT, 85). Median age at diagnosis was 23 years (range 4–75) for PGNT, 27 years (range 6–79) for RGNT, and 40 years (range 2–65) for GNTNI. Ninety-seven percent of PGNT and 69% of GNTNI were located in the supratentorial region, 23% of GNTNI were in the spinal cord, and 80% of RGNT were localized in the posterior fossa. Complete resection was reported in 52 PGNT (73%), 36 RGNT (42%), and 7 GNTNI (27%) patients. Eight PGNT, 3 RGNT, and 12 GNTNI patients were treated with chemo- and/or radiotherapy as the primary postoperative treatment. Follow-up data were available for 132 cases. After a median follow-up time of 1.5 years (range 0.2–25) across all patients, 1.5-year progression-free survival rates were 52±12% for GNTNI, 86±5% for PGNT, and 100% for RGNT. The 1.5-year overall-survival were 95±5%, 98±2%, and 100%, respectively. Conclusions The clinical understanding of the three new entities of glioneuronal tumors, PGNT, RGNT and GNTNI, is currently emerging. The present meta-analysis will hopefully contribute to a delineation of their diagnostic, therapeutic, and prognostic profiles. However, the available data do not provide a solid basis to define the optimum treatment approach. Hence, a central register should be established. PMID:24991807

  14. Characteristics of liver on magnetic resonance diffusion-weighted imaging: Dynamic and image pathological investigation in rabbit liver VX-2 tumor model

    PubMed Central

    Yuan, You-Hong; Xiao, En-Hua; Liu, Jian-Bin; He, Zhong; Jin, Ke; Ma, Cong; Xiang, Jun; Xiao, Jian-Hua; Chen, Wei-Jian

    2008-01-01

    AIM: To investigate dynamical and image pathological characteristics of the liver on magnetic resonance (MR) diffusion-weighted imaging (DWI) in the rabbit VX-2 tumor model. METHODS: Forty New Zealand rabbits were included in the study and VX-2 tumor piece was implanted intrahepatically. Fifteen animals received two intrahepatic implantations while 25 had one intrahepatical implantation. DWI, T1- and T2-weighted of magnetic resonance imaging (MRI) were carried out on the 7th and the 14th d after implantation and DWI was conducted, respectively on the 21th d. Ten VX-2 tumor samples were studied pathologically. RESULTS: The rate of lump detected by DWI, T1WI and T2WI was 78.7%, 10.7% and 53.5% (χ2 = 32.61, P < 0.001) on the 7th d after implantation and 95.8%, 54.3% and 82.9% (χ2 = 21.50, P < 0.001) on the 14th d. The signal of most VX-2 tumors on DWI was uniform and it was equal on the map of apparent diffusion coefficient (ADC). The signal of VX tumors did not decrease on the 7th d after implantation, most of them slowly growing during the week following implantation without significant cell dying within the tumor. VX-2 tumors grew increasingly within 14 d after implantation but the signal of most VX-2 tumors on DWI or on the map of ADC was uniform or uneven and ADC of VX tumors decreased obscurely or slightly because tumor necrosis was still not obvious. On the 21th d after implantation, the signal of most VX-2 tumors on DWI or on the map of ADC was uneven because tumor necrosis was evident and ADC of VX-2 tumor necrotic areas decreased. The areas of viable cells in VX-2 tumors manifested a high signal on DWI and a low signal on the map of ADC. The areas of dead cells or necrosis in VX-2 tumors manifested low signals on DWI and low, equal or high signals on the map of ADC but they manifested high signals on DWI and on the map of ADC at the same time when the areas of necrotic tumor became liquefied or cystic. The border of tumors on DWI appeared gradually

  15. Racial and Ethnic Differences in Breast Cancer Survival: Mediating Effect of Tumor Characteristics and Sociodemographic and Treatment Factors

    PubMed Central

    Warner, Erica T.; Tamimi, Rulla M.; Hughes, Melissa E.; Ottesen, Rebecca A.; Wong, Yu-Ning; Edge, Stephen B.; Theriault, Richard L.; Blayney, Douglas W.; Niland, Joyce C.; Winer, Eric P.; Weeks, Jane C.; Partridge, Ann H.

    2015-01-01

    Purpose To evaluate the relationship between race/ethnicity and breast cancer–specific survival according to subtype and explore mediating factors. Patients and Methods Participants were women presenting with stage I to III breast cancer between January 2000 and December 2007 at National Comprehensive Cancer Network centers with survival follow-up through December 2009. Cox proportional hazards regression was used to compare breast cancer–specific survival among Asians (n = 533), Hispanics (n = 1,122), and blacks (n = 1,345) with that among whites (n = 14,268), overall and stratified by subtype (luminal A like, luminal B like, human epidermal growth factor receptor 2 type, and triple negative). Model estimates were used to derive mediation proportion and 95% CI for selected risk factors. Results In multivariable adjusted models, overall, blacks had 21% higher risk of breast cancer–specific death (hazard ratio [HR], 1.21; 95% CI, 1.00 to 1.45). For estrogen receptor–positive tumors, black and white survival differences were greatest within 2 years of diagnosis (years 0 to 2: HR, 2.65; 95% CI, 1.34 to 5.24; year 2 to end of follow-up: HR, 1.50; 95% CI, 1.12 to 2.00). Blacks were 76% and 56% more likely to die as a result of luminal A–like and luminal B–like tumors, respectively. No disparities were observed for triple-negative or human epidermal growth factor receptor 2–type tumors. Asians and Hispanics were less likely to die as a result of breast cancer compared with whites (Asians: HR, 0.56; 95% CI, 0.37 to 0.85; Hispanics: HR, 0.74; 95% CI, 0.58 to 0.95). For blacks, tumor characteristics and stage at diagnosis were significant disparity mediators. Body mass index was an important mediator for blacks and Asians. Conclusion Racial disparities in breast cancer survival vary by tumor subtype. Interventions are needed to reduce disparities, particularly in the first 2 years after diagnosis among black women with estrogen receptor–positive tumors. PMID

  16. A Strategic Approach to Aggression.

    ERIC Educational Resources Information Center

    Archer, John

    2001-01-01

    Discusses two issues raised by Underwood et al.: the distinction between indirect and relational forms of aggression, and implications of indirect aggression for definitions of aggression; and the normative view of aggression that indicates that aggressive individuals may be socially skilled. Suggests that both issues lead to the conclusion that…

  17. Tumor Mechanics and Metabolic Dysfunction

    PubMed Central

    Tung, Jason C.; Barnes, J. Matthew; Desai, Shraddha R.; Sistrunk, Christopher; Conklin, Matthew; Schedin, Pepper; Keely, Patricia J.; Seewaldt, Victoria L.; Weaver, Valerie M.

    2015-01-01

    Desmosplasia is a characteristic of most solid tumors and leads to fibrosis through abnormal extracellular matrix (ECM) deposition, remodeling and post translational modifications. The resulting stiff tumor stroma not only compromises vascular integrity to induce hypoxia and impede drug delivery, but also promotes aggressiveness by potentiating the activity of key growth, invasion, and survival pathways. Intriguingly, many of the pro-tumorigenic signaling pathways which are mechanically activated by ECM stiffness also promote glucose uptake and aerobic glycolysis, and an altered metabolism is a recognized hallmark of cancer. Indeed, emerging evidence suggests that metabolic alterations and an abnormal ECM may cooperatively drive cancer cell aggression and treatment resistance. Accordingly, improved methods to monitor tissue mechanics and metabolism promise to improve diagnostics and treatments to ameliorate ECM stiffening and elevated mechanosignaling may improve patient outcome. Here we discuss the interplay between ECM mechanics and metabolism in tumor biology and suggest that monitoring these processes and targeting their regulatory pathways may improve diagnostics, therapy, and the prevention of malignant transformation. PMID:25532934

  18. Characteristics of magnetic labeling on liver tumors with anti-alpha-fetoprotein-mediated Fe3O4 magnetic nanoparticles.

    PubMed

    Huang, Kai-Wen; Chieh, Jen-Jie; Horng, Herng-Er; Hong, Chin-Yih; Yang, Hong-Chang

    2012-01-01

    For preoperative and intraoperative detection of tumor distribution, numerous multimodal contrast agents, such as magnetic nanoparticles (MNPs) with several examination indicators, are currently in development. However, complex materials, configuration, and cost are required for multimodal contrast agents, accompanied by a high possibility of toxicity and low popularity in clinics. Nevertheless, the magnetic labeling of MNPs using bioprobes should be feasible not only in preoperative magnetic resonance imaging (MRI), but also in intraoperative examination based on other magnetic properties. In this study, anti-alpha-fetoprotein (AFP)-mediated Fe(3)O(4) MNPs, injected into mice with liver tumors, were used to examine the characteristics of magnetic labeling. Using MRI and scanning superconducting-quantum-interference-device biosusceptometry (SSB), based on alternating current (AC) susceptibility, the magnetic labeling occurred significantly on the first day post-injection of anti-AFP magnetic fluid (MF), and then decreased over time. However, for both MF without antibodies and an anti-carcinoembryonic antigen MF, no magnetic labeling occured on the first day of their respective post-injection. The favorable agreement indicates that magnetic labeling possesses two magnetic characteristics: distortion of the imaging field and AC susceptibility. In addition, the results of the biopsy tests, anti-AFP staining, and Prussian blue staining show the same dynamics as those of magnetic methodologies and prove that bound MNPs on tumor tissue are rotatable by an AC magnetic field to express AC susceptibility. Therefore, with the simple configuration of antibody-mediated MNPs, magnetic labeling is also feasible for intraoperative examinations using SSB with high mobility and sensitivity. PMID:22787394

  19. Girls' Aggressive Behavior

    ERIC Educational Resources Information Center

    Owens, Larry; Shute, Rosalyn; Slee, Phillip

    2004-01-01

    In contrast to boys' bullying behavior which is often overt and easily visible, girls' aggression is usually indirect and covert. Less research has been conducted on the types of bullying that girls usually engage in. Using focus groups composed of teenaged girls, Dr. Owens and colleagues examine the nature of teenage girls' indirect aggression.

  20. Third Person Instigated Aggression.

    ERIC Educational Resources Information Center

    Gaebelein, Jacquelyn

    Since many acts of aggression in society are more than simply an aggressor-victim encounter, the role played by third person instigated aggression also needs examination. The purpose of this study was to develop a laboratory procedure to systematically investigate instigation. In a competitive reaction time task, high and low Machiavellian Males…

  1. Social Aggression among Girls.

    ERIC Educational Resources Information Center

    Underwood, Marion K.

    Noting recent interest in girls' social or "relational" aggression, this volume offers a balanced, scholarly analysis of scientific knowledge in this area. The book integrates current research on emotion regulation, gender, and peer relations, to examine how girls are socialized to experience and express anger and aggression from infancy through…

  2. Origin of craniopharyngiomas: implications for growth pattern, clinical characteristics, and outcomes of tumor recurrence.

    PubMed

    Bao, Yun; Pan, Jun; Qi, Song-Tao; Lu, Yun-Tao; Peng, Jun-Xiang

    2016-07-01

    OBJECT Craniopharyngiomas are associated with a high rate of recurrence. The surgical management of recurrent lesions has been among the most challenging neurosurgical procedures because of the craniopharyngioma's complex topographical relationship with surrounding structures. The aim of this study was to define the determinative role of the site of origin on the growth pattern and clinical features of recurrent craniopharyngiomas. METHODS The authors performed a retrospective analysis of 52 patients who had undergone uniform treatment by a single surgeon. For each patient, data concerning symptoms and signs, imaging features, hypothalamic-pituitary function, and recurrence-free survival rate were collected. RESULTS For children, delayed puberty was more frequent in the group with Type I (infradiaphragmatic) craniopharyngioma than in the group with Type TS (tuberoinfundibular and suprasellar extraventricular) lesions (p < 0.05). For adults, blindness was more frequent in the Type I group than in the Type TS group (p < 0.05). Nausea or vomiting, delayed puberty, and growth retardation were more frequent in children than in adults (p < 0.05). Overall clinical outcome was good in 48.07% of the patients and poor in 51.92%. Patients with Type TS recurrent tumors had significantly worse functional outcomes and hypothalamic function than patients with the Type I recurrent tumors but better pituitary function especially in children. CONCLUSIONS The origin of recurrent craniopharyngiomas significantly affected the symptoms, signs, functional outcomes, and hypothalamic-pituitary functions of patients undergoing repeated surgery. Differences in tumor growth patterns and site of origin should be considered when one is comparing outcomes and survival across treatment paradigms in patients with recurrent craniopharyngiomas. PMID:26654183

  3. Assessment of aggression in inpatient settings.

    PubMed

    McDermott, Barbara E; Holoyda, Brian J

    2014-10-01

    The threat of violence is a major concern for all individuals working or receiving treatment in an inpatient psychiatric setting. One major focus in forensic psychology and psychiatry over the past several decades has been the development of risk assessments to aid in the identification of those individuals most at risk of exhibiting violent behavior. So-called second- and third-generation risk assessments were developed to improve the accuracy of decision making. While these instruments were developed for use in the community, many have proven to be effective in identifying patients more likely to exhibit institutional aggression. Because the purpose of risk assessment is the reduction of violence, dynamic factors were included in third-generation risk instruments to provide opportunities for intervention and methods for measuring change. Research with these instruments indicates that both static factors (second-generation) and dynamic factors (third-generation) are important in identifying those patients most likely to engage in institutional aggression, especially when the aggression is categorized by type (impulsive/reactive, organized/predatory/instrumental, psychotic). Recent research has indicated that developing a typology of aggressive incidents may provide insight both into precipitants to assaults as well as appropriate interventions to reduce such aggression. The extant literature suggests that both static and dynamic risk factors are important, but may be differentially related to the type of aggression exhibited and the characteristics of the individuals exhibiting the aggression. PMID:25296966

  4. Benign bone tumors.

    PubMed

    Steffner, Robert

    2014-01-01

    Benign bone lesions are a broad category that demonstrates a spectrum of activities from latent to aggressive. Differentiating the various tumors is important in order to properly determine necessary intervention. This chapter focuses on the presentation, imaging, diagnostic features, and treatment of the most common benign bone tumors in order to help guide diagnosis and management. PMID:25070230

  5. Clinical Characteristics and Outcomes of Pediatric Patients with Desmoplastic Small Round Cell Tumor

    PubMed Central

    Bent, Melissa A.; Padilla, Benjamin E.; Goldsby, Robert E.; DuBois, Steven G.

    2016-01-01

    Desmoplastic small round cell tumor (DSRCT) is a rare malignancy that typically affects pediatric and young adult patients. There are limited data on the clinical features of pediatric DSRCT. We selected patients aged 0-21 years reported to the Surveillance, Epidemiology and End Results Program from 1991-2011. We estimated overall survival using Kaplan-Meier approaches and compared outcomes using the log rank test. The median age of the 95 pediatric patients was 15.3 years (range: 0-21). The majority of tumors originated in the abdomen and pelvis (84.4%) and the majority of patients had distant metastasis (72.6%). A minority of patients received radiation (34%). Overall survival at 5 years was poor (18.1%; 95% confidence interval 10.1-27.9%). Radiation therapy was associated with superior survival. Pediatric patients with DSRCT have significant disease burden. Outcomes for children are poor, though patients selected for radiation appear to have improved survival. PMID:27134714

  6. Linneg Sca-1high CD49fhigh prostate cancer cells derived from the Hi-Myc mouse model are tumor-initiating cells with basal-epithelial characteristics and differentiation potential in vitro and in vivo.

    PubMed

    Saha, Achinto; Blando, Jorge; Fernandez, Irina; Kiguchi, Kaoru; DiGiovanni, John

    2016-05-01

    A cell line was established from ventral prostate (VP) tumors of one-year-old Hi-Myc mice. These cells, called HMVP2 cells, are LinnegSca-1highCD49fhigh with high CD44 and CD29 expression and express CK14, Sca-1 and CD49f (but not CK8), suggesting basal-epithelial characteristics. Furthermore, HMVP2 cells form spheroids and both the cells and spheroids produce tumors in syngeneic mice. After four days of culture, HMVP2 spheroids underwent a gradual transition from LinnegSca-1highCD49fhigh expression to LinnegSca-1lowCD49flow while a subpopulation of the cells retained the original LinnegSca-1highCD49fhigh expression pattern. Additional cell subpopulations expressing Lin positive markers were also present suggesting further differentiation of HMVP2 spheroids. Two additional highly tumorigenic cell lines (HMVP2A1 and HMVP2A2) were isolated from HMVP2 cells after subsequent tumor formation in FVB/N mice. Concurrently, we also established cell lines from the VP of 6 months old Hi-Myc mice (named as HMVP1) and FVB/N mice (called NMVP) having less aggressive growth properties compared to the other three cell lines. AR expression was reduced in HMVP2 cells compared to NMVP and HMVP1 cells and almost absent in HMVP2A1 and HMVP2A2 cells. These cell lines will provide valuable tools for further mechanistic studies as well as preclinical studies to evaluate preventive and/or therapeutic agents for prostate cancer.

  7. Linneg Sca-1high CD49fhigh prostate cancer cells derived from the Hi-Myc mouse model are tumor-initiating cells with basal-epithelial characteristics and differentiation potential in vitro and in vivo

    PubMed Central

    Fernandez, Irina; Kiguchi, Kaoru; DiGiovanni, John

    2016-01-01

    A cell line was established from ventral prostate (VP) tumors of one-year-old Hi-Myc mice. These cells, called HMVP2 cells, are LinnegSca-1highCD49fhigh with high CD44 and CD29 expression and express CK14, Sca-1 and CD49f (but not CK8), suggesting basal-epithelial characteristics. Furthermore, HMVP2 cells form spheroids and both the cells and spheroids produce tumors in syngeneic mice. After four days of culture, HMVP2 spheroids underwent a gradual transition from LinnegSca-1highCD49fhigh expression to LinnegSca-1lowCD49flow while a subpopulation of the cells retained the original LinnegSca-1highCD49fhigh expression pattern. Additional cell subpopulations expressing Lin positive markers were also present suggesting further differentiation of HMVP2 spheroids. Two additional highly tumorigenic cell lines (HMVP2A1 and HMVP2A2) were isolated from HMVP2 cells after subsequent tumor formation in FVB/N mice. Concurrently, we also established cell lines from the VP of 6 months old Hi-Myc mice (named as HMVP1) and FVB/N mice (called NMVP) having less aggressive growth properties compared to the other three cell lines. AR expression was reduced in HMVP2 cells compared to NMVP and HMVP1 cells and almost absent in HMVP2A1 and HMVP2A2 cells. These cell lines will provide valuable tools for further mechanistic studies as well as preclinical studies to evaluate preventive and/or therapeutic agents for prostate cancer. PMID:26910370

  8. Linneg Sca-1high CD49fhigh prostate cancer cells derived from the Hi-Myc mouse model are tumor-initiating cells with basal-epithelial characteristics and differentiation potential in vitro and in vivo.

    PubMed

    Saha, Achinto; Blando, Jorge; Fernandez, Irina; Kiguchi, Kaoru; DiGiovanni, John

    2016-05-01

    A cell line was established from ventral prostate (VP) tumors of one-year-old Hi-Myc mice. These cells, called HMVP2 cells, are LinnegSca-1highCD49fhigh with high CD44 and CD29 expression and express CK14, Sca-1 and CD49f (but not CK8), suggesting basal-epithelial characteristics. Furthermore, HMVP2 cells form spheroids and both the cells and spheroids produce tumors in syngeneic mice. After four days of culture, HMVP2 spheroids underwent a gradual transition from LinnegSca-1highCD49fhigh expression to LinnegSca-1lowCD49flow while a subpopulation of the cells retained the original LinnegSca-1highCD49fhigh expression pattern. Additional cell subpopulations expressing Lin positive markers were also present suggesting further differentiation of HMVP2 spheroids. Two additional highly tumorigenic cell lines (HMVP2A1 and HMVP2A2) were isolated from HMVP2 cells after subsequent tumor formation in FVB/N mice. Concurrently, we also established cell lines from the VP of 6 months old Hi-Myc mice (named as HMVP1) and FVB/N mice (called NMVP) having less aggressive growth properties compared to the other three cell lines. AR expression was reduced in HMVP2 cells compared to NMVP and HMVP1 cells and almost absent in HMVP2A1 and HMVP2A2 cells. These cell lines will provide valuable tools for further mechanistic studies as well as preclinical studies to evaluate preventive and/or therapeutic agents for prostate cancer. PMID:26910370

  9. Aggressive behaviors in the psychiatric emergency service

    PubMed Central

    Chaput, Yves; Beaulieu, Lucie; Paradis, Michel; Labonté, Edith

    2011-01-01

    Introduction: Studies of aggressive behaviors in a nonforensic mental health setting have focused primarily on the inpatient ward and, on event prediction, using behavior-based clinical rating scales. Few studies have specifically targeted aggressive behaviors in the psychiatric emergency service or determined whether assessing the demographic and clinical characteristics of such patients might prove useful for their more rapid identification. Methods: We used a prospectively acquired database of over 20,900 visits to four services in the province of Quebec, Canada, over a two-year period from September 2002 onwards. A maximum of 72 variables could be acquired per visit. Visits with aggression (any verbally or physically intimidating behavior), both present and past, were tagged. Binary logistic regressions and cross-tabulations were used to determine whether the profile of a variable differed in visits with aggression from those without aggression. Results: About 7% of visits were marked by current aggression (verbal 49%, physical 12%, verbal and physical 39%). Including visits with a “past only” history of aggression increased this number to 20%. Variables associated with aggression were gender (male), marital status (single/separated), education (high school or less), employment (none), judicial history (any type), substance abuse (prior or active), medication compliance (poor), type of arrival to psychiatric emergency services (involuntary, police, judiciary, landlord), reason for referral (behavioral dyscontrol), diagnosis (less frequent in anxiety disorders), and outcome (more frequently placed under observation or admitted). Conclusion: Our results suggest that many state-independent variables are associated with aggressive behaviors in the psychiatric emergency service. Although their sum may not add up to a specific patient profile, they can nevertheless be useful in service planning, being easily integrated alongside state-dependent rating scales in a

  10. Chronobiological characteristics of the action of thyroxine of reproduction of Ehrlich's Ascites Tumor cells

    SciTech Connect

    Stepanenko, V.A.; Romanov, Y.A.

    1985-05-01

    This paper studies the action of thyroxine on cell proliferation in a hyperdiploid strain of Ehrlich's Ascites Tumor (EAT) depending on clock time. Five albino mice were given an injection of tritium-thymidine in a dose of 0.5 u Ci/g body weight (specific radioactivity 4.1 Ci/mmole) one hour before sacrifice. On autoradiographs from each animal, during examination of 3000-5000 cells, the number of dividing and DNA-synthesizing cells was counted and mitotic index and radioactive index were calculated and expressed in promille. Parameters method and the results were subjected to statistical analysis by the Fisher-Student method. Differences were considered significant at the P less than 0.05 level.

  11. Aggression and Anxiety: Social Context and Neurobiological Links

    PubMed Central

    Neumann, Inga D.; Veenema, Alexa H.; Beiderbeck, Daniela I.

    2009-01-01

    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) vs. 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. PMID:20407578

  12. [Aggressive behavior: theoretical and biological aspects].

    PubMed

    Giotakos, O

    2013-01-01

    The susceptibility to aggression may manifest differently depending on the psychological context in which it occurs. In the context of psychopathy, characterized by a lack of empathy, this may manifest in aggression with criminal acts, which is characteristic of antisocial personality disorder. When the susceptibility is associated with psychotic impairment, aggression may be manifested in highly deviant behavior, like murder or serial killing. While the great majority of persons with schizophrenia do not commit violent acts, clinicians suggest that some schizophrenics may pose a risk in the community, particularly those patients with co-occurring substance abuse diagnoses, those who are noncompliant with prescribed psychiatric treatment, and those with a history of frequent relapses resulting in hospitalization or arrest. Episodic violence and aggression often accompany dementia. When coupled with emotional dysregulation, impulsive aggression often occurs in an interpersonal context, as in borderline personality disorder. However, the most common comorbidity is the substance abuse disorder, which contributes to both the cognitive distortions and disinhibition associated with the substance use. According to the biological data, aggression seems to emerge when the drive of limbic-mediated affective prefrontal response to provocative producing stimuli is insufficiently constrained by inhibition. Thus, excessive reactivity in the amygdale, coupled with inadequate prefrontal regulation, increase the possibility of aggressive behavior. The PET/SPECT studies focusing on schizophrenia have shown reduced activity in fronto-temoral circuitry. The fMRI studies concord with the hypothesis that among violent persons with schizophrenia, those with sociopathetic features and/or substance abuse constitute a highly different subgroup, in which cognitive, neurological and behavioral patterns are more closely associated with the personality traits than schizophrenia. It is known

  13. Solitary fibrous tumor of the upper respiratory tract. A report of six cases.

    PubMed

    Witkin, G B; Rosai, J

    1991-09-01

    We report six cases of a neoplasm that arose in the upper respiratory tract and had a histological appearance indistinguishable from that of solitary fibrous tumor of the pleura (SFT, so-called fibrous mesothelioma). The patients were adults who presented with nasal obstruction. The lesions lacked the characteristic features of other recognized neoplasms that occur in this region. The tumor cells were immunoreactive for vimentin but not for keratin. The occurrence of SFT in this location further supports the argument that SFT is a tumor of mesenchymal and not mesothelial origin. None of the tumors in this series had the histologic features of malignancy described for SFT in other locations, and there was no aggressive behavior in limited follow-up. Until more cases of SFT in unusual locations have been studied, we recommend that the same criteria used for assessing aggressiveness in SFT of the pleura be applied to them.

  14. Some Characteristics of DNA Synthesis and the Mitotic Cycle in Ehrlich Ascites Tumor Cells

    PubMed Central

    Edwards, Joshua L.; Koch, Arthur L.; Youcis, Pauline; Freese, Herbert L.; Laite, Melville B.; Donalson, J. Thomas

    1960-01-01

    In vivo studies of Ehrlich ascites tumor cells during the first 5 days of growth in peritoneal cavities of mice consisted of the following: 1. Determination of growth curves by direct enumeration of cells. 2. Estimation of the duration of each phase of the mitotic cycle based on incidence of cells in different phases. 3. Radioautographic studies to determine the proportion of cells in different phases of the mitotic cycle that incorporate tritiated thymidine during a single brief exposure to this precursor of DNA. 4. Estimation of the rate of incorporation of tritiated thymidine at different times during the period of DNA synthesis by comparison of mean grain counts over nuclei in radioautographs at different times following exposure to tritiated thymidine. The assumptions underlying these experiments and our observations concerning the duration of the period of DNA synthesis and its relation to the mitotic cycle are discussed. It is concluded that DNA synthesis is continuous, occupying a period of 8.5 hours during the interphase and that the average rate of synthesis is approximately constant. PMID:13819420

  15. Spectrophotometric Determination of the Characteristics of Stromal and Parenchymal Components of Colon Tumors

    NASA Astrophysics Data System (ADS)

    Motevich, I. G.; Strekal, N. D.; Shulha, A. V.; Maskevich, S. A.

    2016-05-01

    We consider the dependence of the spectral properties of eosin and hematoxylin (dyes routinely used in histology as contrast agents) on their localization in biological tissues with different levels of pathology: benign and malignant neoplasms and sigmoid colonic crypts. We have analyzed the fluorescent images and fluorescence spectra of the parenchyma and stromal elements. We have established that on going from physiologically normal cells to tumor cells, the contribution to the absorption cross section of histologic sections due to hematoxylin increases. In pathologically altered cells in a colonic crypt, we observe a hypsochromic effect in the fluorescence spectra of the samples with appreciable quenching of the fluorescence, while in the model systems the reverse effect occurs: a shift of the fluorescence maximum toward the red region. We discuss the influence on the indicated effects from local pH and the polarity of the dye environment in the model systems and histologic sections. As the systems modeling the polarity and acidity of the biological media, we use aqueous solutions of the dyes with different pH values and synthetic polyelectrolytes.

  16. Cancer-Associated Fibroblasts: Their Characteristics and Their Roles in Tumor Growth

    PubMed Central

    Shiga, Kazuyoshi; Hara, Masayasu; Nagasaki, Takaya; Sato, Takafumi; Takahashi, Hiroki; Takeyama, Hiromitsu

    2015-01-01

    Cancer tissues are composed of cancer cells and the surrounding stromal cells (e.g., fibroblasts, vascular endothelial cells, and immune cells), in addition to the extracellular matrix. Most studies investigating carcinogenesis and the progression, invasion, metastasis, and angiogenesis of cancer have focused on alterations in cancer cells, including genetic and epigenetic changes. Recently, interactions between cancer cells and the stroma have attracted considerable attention, and increasing evidence has accumulated on this. Several researchers have gradually clarified the origins, features, and roles of cancer-associated fibroblasts (CAFs), a major component of the cancer stroma. CAFs function in a similar manner to myofibroblasts during wound healing. We previously reported the relationship between CAFs and angiogenesis. Interleukin-6 (IL-6), a multifunctional cytokine, plays a central role in regulating inflammatory and immune responses, and important roles in the progression, including proliferation, migration, and angiogenesis, of several cancers. We showed that CAFs are an important IL-6 source and that anti-IL-6 receptor antibody suppressed angiogenesis and inhibited tumor-stroma interactions. Furthermore, CAFs contribute to drug-resistance acquisition in cancer cells. The interaction between cancer cells and the stroma could be a potential target for anti-cancer therapy. PMID:26690480

  17. Aggression in Pretend Play and Aggressive Behavior in the Classroom

    ERIC Educational Resources Information Center

    Fehr, Karla K.; Russ, Sandra W.

    2013-01-01

    Research Findings: Pretend play is an essential part of child development and adjustment. However, parents, teachers, and researchers debate the function of aggression in pretend play. Different models of aggression predict that the expression of aggression in play could either increase or decrease actual aggressive behavior. The current study…

  18. Denial of Suffering in the Victim as a Stimulus to Violence in Aggressive Boys

    ERIC Educational Resources Information Center

    Perry, David G.; Perry, Louise C.

    1974-01-01

    The effects of magnitude of victim's pain cues, the subject's characteristic lead of aggressiveness, and the level of prior anger arousal on aggressive behavior was studied in the elementary school boys. (ST)

  19. Characteristics of phenol. Instillation in intralesional tumor excision of chondroblastoma, osteoclastoma and enchondroma.

    PubMed

    Quint, U; Müller, R T; Müller, G

    1998-01-01

    Because of the typical metaphyseal-epiphyseal growth of giant cell tumors and chondroblastomas, the optimal result of an en bloc resection can usually only be achieved by a loss of joint function. For this reason, intralesional excision has prevailed, though it leads to a high rate of relapses. Adjuvant therapy involving irrigation of the remaining bone cavity with phenol can distinctly decrease the rate of relapse. Little is known about the amount of phenol applied that is absorbed. This study investigated the urinary excretion of phenol following the instillation of 102 ml of a 5% phenol solution. The method consisted of urine collection from 11 patients treated by phenol instillation preoperatively, and at 1, 3, 6, 12 and 24 h postoperatively. The urine specimens were analysed for phenol by mass spectrometry. Preoperatively, the value was 5.1 mg/l on average. The maximum concentration of 62 mg/l was found 1 h after instillation, with an average value of 41.5 mg/l, and after 3 h of 18.9 mg/l. A further rapid decrease in the excretion rate was recorded, with normal values being reached after 12 h. This means a maximum of 9% and an average of 2% of the instilled amount of phenol were excreted in the urine within 24 h postoperatively. By comparing these urinary concentrations to published standards, we conclude that the instillation of a 5% phenol solution into bony lesions is associated with a relatively low risk of systemic toxicity. PMID:9457335

  20. Examination of ancestral informative markers and self-reported race with tumor characteristics of breast cancer among black and white women

    PubMed Central

    Reding, Kerryn W.; Carlson, Christopher S.; Kahsai, Orsalem; Chen, Christina C.; McDavid, Andrew; Doody, David R.; Chen, Chu; Ornelas, India; Lowe, Kimberly; Bernstein, Leslie; Weiss, Linda; McDonald, Jill A.; Simon, Michael S.; Strom, Brian; Marchbanks, Polly A.; Burkman, Ronald; Spirtas, Robert; Liff, Jonathan M.; Malone, Kathleen E.

    2013-01-01

    Background African American (AA) women have a higher mortality from breast cancer (BC) compared to European American (EA) women. This may be due to the higher proportion of AA women with tumors that are diagnosed at more advanced stages and are characterized as being estrogen receptor negative (ER-)/ progesterone receptor negative (PR-). Our study sought to determine whether self-reported race and percent African ancestry were associated with BC tumor characteristics. Methods In a multi-center, population-based case-control study of BC, we determined percent African ancestry using ancestry informative markers (AIM) among women self-reporting race as AA or Black. Results BC tumor characteristics were associated with self-reported race (including a 30% reduction in ER+/PR+ tumors [95% confidence interval [CI]: 0.6-0.9] and a 1.5-fold increased risk of high grade [95% CI: 1.2-1.9] for AA women compared to EA women). AIMs among AA women were not associated with BC tumor characteristics (AA women with ≥ 95% versus < 80% African ancestry, odds ratio [OR]=1.0 for ER+/PR+ [95% CI: 0.6-1.8] and OR=0.9 for high-grade tumors [95% CI: 0.6-1.4]). Similar findings were observed for BC stage. Conclusion While BC subtypes were associated with self-reported race, BC subtypes were not associated with percent African ancestry. Impact These study results suggest that subtle differences in percent African ancestry are less important than the overall presence of African ancestry in relation to BC tumor characteristics. PMID:22648732

  1. Prognosis by tumor location in adults with intracranial ependymomas.

    PubMed

    Sayegh, Eli T; Aranda, Derick; Kim, Joseph M; Oh, Taemin; Parsa, Andrew T; Oh, Michael C

    2014-12-01

    Intracranial ependymomas are rare tumors in adults. Thus, factors affecting prognosis are poorly understood. We performed a study to investigate whether tumor location is an important prognostic factor in adults who undergo surgery for intracranial ependymomas. PubMed was searched to identify studies that reported clinical outcomes in adult patients with intracranial ependymoma. Data were extracted for patient and tumor characteristics, extent of resection, progression-free survival (PFS), and overall survival (OS). Tumors were categorized as supratentorial or infratentorial and extraventricular or intraventricular. Presenting clinical features and tumor characteristics were tabulated. Kaplan-Meier and multivariate Cox regression survival analyses were performed to determine PFS and OS by tumor location. Extent of resection was also analyzed by tumor location. A total of 183 patients were included in the meta-analysis. Patients presented at a mean of 8.2months with a myriad of clinical features. The mean tumor size was 3.38 cm, and 19.3% of tumors were cystic. Supratentorial tumors were most commonly located in the frontal and parietal lobes, and infratentorial tumors in the fourth ventricle. Supratentorial tumors demonstrated significantly poorer PFS (p<0.001) and OS (p=0.003) than infratentorial tumors, despite a higher rate of gross total resection (GTR) for the supratentorial tumors (72.6% versus 42.1%). Extraventricular ependymomas displayed significantly poorer PFS than intraventricular ependymomas (p=0.009). In summary, supratentorial ependymomas have significantly poorer PFS and OS than their infratentorial counterparts, despite being more conducive to GTR, suggesting increased clinical aggressiveness. Extraventricular location is also associated with significantly poorer PFS than intraventricular location.

  2. Aggression in Drosophila.

    PubMed

    Kravitz, Edward A; Fernandez, Maria de la Paz

    2015-10-01

    Aggression is used by essentially all species of animals to gain access to desired resources, including territory, food, and potential mates: Fruit flies are no exception. In Drosophila, both males and females compete in same sex fights for resources, but only males establish hierarchical relationships. Many investigators now study aggression using the fruit fly model, mainly because (a) aggression in fruit flies is a quantifiable well-defined and easily evoked behavior; (b) powerful genetic methods allow investigators to manipulate genes of interest at any place or time during embryonic, larval, pupal or adult life, and while flies are behaving; (c) the growth of the relatively new field of optogenetics makes physiological studies possible at single neuron levels despite the small sizes of neurons and other types of cells in fly brains; and (d) the rearing of fly stocks with their short generation times and limited growth space requirements can easily be performed at relatively low cost in most laboratories. This review begins with an examination of the behavior, both from a historical perspective and then from the birth of the "modern" era of studies of aggression in fruit flies including its quantitative analysis. The review continues with examinations of the roles of genes, neurotransmitters and neurohormones, peptides, nutritional and metabolic status, and surface cuticular hydrocarbons in the initiation and maintenance of aggression. It concludes with suggestions for future studies with this important model system.

  3. Brief report: Physical health of adolescent perpetrators of sibling aggression.

    PubMed

    Tucker, Corinna Jenkins; Van Gundy, Karen; Sharp, Erin Hiley; Rebellon, Cesar

    2015-12-01

    We describe adolescents' perpetration of sibling aggression and its link to physical health two years later. In-school surveys at Time 1 (N = 331) and Time 2 (two-years later, N = 283) were administered to adolescents (at Time 1, Mage = 15.71 years, SD = .63; 52% female) living in the United States querying about perpetration of aggression toward a sibling closest in age and perceived physical health. The majority of adolescents perpetrated aggression towards their sibling (74%). Adolescents who were part of brother-brother pairs reported the most aggression. Hierarchical regression analysis showed that perpetrating sibling aggression more often at Time 1 was predictive of lower physical health at Time 2 controlling for Time 1 physical health and demographic characteristics. Perpetration of aggression toward a sibling is common and has negative health consequences in late adolescence suggesting this issue should be targeted to improve adolescents' sibling dynamics and physical health.

  4. Surgical treatment of aggressive vertebral hemangiomas.

    PubMed

    Vasudeva, Viren S; Chi, John H; Groff, Michael W

    2016-08-01

    OBJECTIVE Vertebral hemangiomas are common tumors that are benign and generally asymptomatic. Occasionally these lesions can exhibit aggressive features such as bony expansion and erosion into the epidural space resulting in neurological symptoms. Surgery is often recommended in these cases, especially if symptoms are severe or rapidly progressive. Some surgeons perform decompression alone, others perform gross-total resection, while others perform en bloc resection. Radiation, embolization, vertebroplasty, and ethanol injection have also been used in combination with surgery. Despite the variety of available treatment options, the optimal management strategy is unclear because aggressive vertebral hemangiomas are uncommon lesions, making it difficult to perform large trials. For this reason, the authors chose instead to report their institutional experience along with a comprehensive review of the literature. METHODS A departmental database was searched for patients with a pathological diagnosis of "hemangioma" between 2008 and 2015. Medical records were reviewed to identify patients with aggressive vertebral hemangiomas, and these cases were reviewed in detail. RESULTS Five patients were identified who underwent surgery for treatment of aggressive vertebral hemangiomas during the specified time period. There were 2 lumbar and 3 thoracic lesions. One patient underwent en bloc spondylectomy, 2 patients had piecemeal gross-total resection, and the remaining 2 had subtotal tumor resection. Intraoperative vertebroplasty was used in 3 cases to augment the anterior column or to obliterate residual tumor. Adjuvant radiation was used in 1 case where there was residual tumor as well. The patient who underwent en bloc spondylectomy experienced several postoperative complications requiring additional medical care and reoperation. At an average follow-up of 31 months (range 3-65 months), no patient had any recurrence of disease and all were clinically asymptomatic, except the

  5. Surgical treatment of aggressive vertebral hemangiomas.

    PubMed

    Vasudeva, Viren S; Chi, John H; Groff, Michael W

    2016-08-01

    OBJECTIVE Vertebral hemangiomas are common tumors that are benign and generally asymptomatic. Occasionally these lesions can exhibit aggressive features such as bony expansion and erosion into the epidural space resulting in neurological symptoms. Surgery is often recommended in these cases, especially if symptoms are severe or rapidly progressive. Some surgeons perform decompression alone, others perform gross-total resection, while others perform en bloc resection. Radiation, embolization, vertebroplasty, and ethanol injection have also been used in combination with surgery. Despite the variety of available treatment options, the optimal management strategy is unclear because aggressive vertebral hemangiomas are uncommon lesions, making it difficult to perform large trials. For this reason, the authors chose instead to report their institutional experience along with a comprehensive review of the literature. METHODS A departmental database was searched for patients with a pathological diagnosis of "hemangioma" between 2008 and 2015. Medical records were reviewed to identify patients with aggressive vertebral hemangiomas, and these cases were reviewed in detail. RESULTS Five patients were identified who underwent surgery for treatment of aggressive vertebral hemangiomas during the specified time period. There were 2 lumbar and 3 thoracic lesions. One patient underwent en bloc spondylectomy, 2 patients had piecemeal gross-total resection, and the remaining 2 had subtotal tumor resection. Intraoperative vertebroplasty was used in 3 cases to augment the anterior column or to obliterate residual tumor. Adjuvant radiation was used in 1 case where there was residual tumor as well. The patient who underwent en bloc spondylectomy experienced several postoperative complications requiring additional medical care and reoperation. At an average follow-up of 31 months (range 3-65 months), no patient had any recurrence of disease and all were clinically asymptomatic, except the

  6. Aggressiveness and Disobedience

    ERIC Educational Resources Information Center

    Vaaland, Grete Sorensen; Idsoe, Thormod; Roland, Erling

    2011-01-01

    This study aims to conceptualize disobedient pupil behavior within the more general framework of antisocial behavior and to reveal how two forms of aggressiveness are related to disobedience. Disobedience, in the context of this article, covers disruptive pupil behavior or discipline problems when the pupil is aware of breaking a standard set by…

  7. Neuroimaging and Aggression.

    ERIC Educational Resources Information Center

    Mills, Shari; Raine, Adrian

    1994-01-01

    Brain imaging research allows direct assessment of structural and functional brain abnormalities, and thereby provides an improved methodology for studying neurobiological factors predisposing to violent and aggressive behavior. This paper reviews 20 brain imaging studies using four different types of neuroimaging techniques that were conducted in…

  8. Intellectual Competence and Aggression.

    ERIC Educational Resources Information Center

    Huesmann, L. Rowell; Yarmel, Patty Warnick

    Using data from a broader longitudinal study, this investigation explores within-subject and cross-generational stability of intellectual competence and the relationship of such stability to aggressive behavior. Data were gathered three times (when subjects' modal age was 8, 19, and 30 years). Initially, subjects included the entire population…

  9. Stability of Aggressive Behavior.

    ERIC Educational Resources Information Center

    Eron, Leonard D.; Huesmann, L. Rowell

    As indicated by multiple measures (including overt criminal behavior), stability of aggressive behavior was investigated across 22 years for males and females in a variety of situations. Originally, subjects included the entire population enrolled in the third grade in a semi-rural county in New York State. The sample included approximately 870…

  10. Relational Aggression among Students

    ERIC Educational Resources Information Center

    Young, Ellie L.; Nelson, David A.; Hottle, America B.; Warburton, Brittney; Young, Bryan K.

    2011-01-01

    "Relational aggression" refers to harm within relationships caused by covert bullying or manipulative behavior. Examples include isolating a youth from his or her group of friends (social exclusion), threatening to stop talking to a friend (the silent treatment), or spreading gossip and rumors by email. This type of bullying tends to be…

  11. Human Aggression and Suicide

    ERIC Educational Resources Information Center

    Brown, Gerald L.; Goodwin, Frederick K

    1986-01-01

    The central nervous system transmitter serontonin may be altered in aggressive/impulsive and suicidal behaviors in humans. These reports are largely consistent with animal data, and constitute one of the most highly replicated set of findings in biological psychiatry. Suggests that some suicidal behavior may be a special kind of aggressive…

  12. Cyber Aggression: The Relation between Online Offenders and Offline Social Competence

    ERIC Educational Resources Information Center

    Schoffstall, Corrie L.; Cohen, Robert

    2011-01-01

    Children are increasingly using computer technologies to engage in acts of aggression against peers, often termed "cyber aggression". Media reports have sensationalized instances of cyber aggression, and social scientists have begun to examine its characteristics and consequences. Using a younger sample of children than most previous research (192…

  13. Who Dislikes Whom, and for Whom Does It Matter: Predicting Aggression in Middle Childhood

    ERIC Educational Resources Information Center

    Erath, Stephen A.; Pettit, Gregory S.; Dodge, Kenneth A.; Bates, John E.

    2009-01-01

    This study investigated the role of mutual dislike dyads (MDDs) in the development of aggressive behavior across the middle childhood years. Of particular interest was whether involvement in MDDs predicted later aggression, and whether the magnitude of the association between MDDs and later aggression varied based on characteristics of target…

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

  16. Apolipoprotein E gene polymorphism influences aggressive behavior in prostate cancer cells by deregulating cholesterol homeostasis

    PubMed Central

    IFERE, GODWIN O.; DESMOND, RENEE; DEMARK-WAHNEFRIED, WENDY; NAGY, TIM R.

    High circulating cholesterol and its deregulated homeostasis may facilitate prostate cancer progression. Genetic polymorphism in Apolipoprotein (Apo) E, a key cholesterol regulatory protein may effect changes in systemic cholesterol levels. In this investigation, we determined whether variants of the Apo E gene can trigger defective intracellular cholesterol efflux, which could promote aggressive prostate cancer. ApoE genotypes of weakly (non-aggressive), moderate and highly tumorigenic (aggressive) prostate cancer cell lines were characterized, and we explored whether the ApoE variants were associated with tumor aggressiveness generated by intra cellular cholesterol imbalance, using the expression of caveolin-1 (cav-1), a pro-malignancy surrogate of cholesterol overload. Restriction isotyping of ApoE isoforms revealed that the non-aggressive cell lines carried ApoE ε3/ε3 or ε3/ε4 alleles, while the aggressive cell lines carried the Apoε2/ε4 alleles. Our data suggest a contrast between the non-aggressive and the aggressive prostate cancer cell lines in the pattern of cholesterol efflux and cav-1 expression. Our exploratory results suggest a relationship between prostate aggressiveness, ApoE isoforms and cholesterol imbalance. Further investigation of this relationship may elucidate the molecular basis for considering cholesterol as a risk factor of aggressive prostate tumors, and underscore the potential of the dysfunctional ApoE2/E4 isoform as a biomarker of aggressive disease. PMID:23934233

  17. Reverse Discrimination and Aggressive Behavior.

    ERIC Educational Resources Information Center

    Johnson, Stephen D.

    1980-01-01

    White subjects were aggressive toward Black opponents when contest results appeared to reflect elements of reverse discrimination; but they showed less aggressive behavior toward Black opponents when they thought their loss was due to their opponents' superior ability. (RL)

  18. Real-time hostile attribution measurement and aggression in children.

    PubMed

    Yaros, Anna; Lochman, John E; Rosenbaum, Jill; Jimenez-Camargo, Luis Alberto

    2014-01-01

    Hostile attributions are an important predictor of aggression in children, but few studies have measured hostile attributions as they occur in real-time. The current study uses an interactive video racing game to measure hostile attributions while children played against a presumed peer. A sample of 75 children, ages 10-13, used nonverbal and verbal procedures to respond to ambiguous provocation by their opponent. Hostile attributions were significantly positively related to parent-rated reactive aggression, when controlling for proactive aggression. Hostile attributions using a nonverbal response procedure were negatively related to proactive aggression, when controlling for reactive aggression. Results suggest hostile attributions in real-time occur quickly and simultaneously with social interaction, which differs from the deliberative, controlled appraisals measured with vignette-based instruments. The relation between real-time hostile attributions and reactive aggression could be accounted for by the impulsive response style that is characteristic of reactive aggression, whereas children exhibiting proactive aggression may be more deliberate and intentional in their responding, resulting in a negative relation with real-time hostile attributions. These findings can be used both to identify children at risk for aggression and to enhance preventive interventions.

  19. Predictors of experiencing aggression in clubs: Beyond alcohol consumption

    PubMed Central

    Miller, Brenda A.; Bourdeau, Beth; Johnson, Mark; Voas, Robert

    2014-01-01

    To examine the social drinking group's influence on the individual's experiences of physical or sexual aggression at clubs, data were collected from 368 groups (N=986 individuals). Both group and individual level indicators were examined for impact on self-reports of physical and sexual aggression experiences while at the club. Recent aggressive experiences and perpetration, concerns for group safety, one's own plans and assessment of other group members' plans to drink to the point of intoxication, and personal characteristics were examined, using both individual and group indicators. At exit, participants reported experiencing physical aggression (12.3%) and sexual aggression (12.6%) at the club. Using generalized linear mixed modeling to account for nested data (club, event, and group), group level indicators predicted both the individual's physical and sexual aggression experiences. Especially for experiences of physical aggression, group effects are notable. Being in a group whose members recently experienced physical aggression, increased the risk for the individual. Interestingly, groups that had higher levels of planned intoxication decreased risks of experiencing aggression, while a discrepancy in these intentions among group members increased the risks. Group effects were also noted for experiencing sexual aggression. High levels of prior experiences for sexual aggression in the group increased the risks for the individual during the event. Also, being in a group that is identified as having at least one member who is frequently drunk, increases the risk for experiencing sexual aggression. These findings inform prevention strategies for young adults engaged in high risk behaviors by targeting social drinking groups who frequent clubs. PMID:24838821

  20. Genital soft tissue tumors.

    PubMed

    Schoolmeester, John K; Fritchie, Karen J

    2015-07-01

    Mesenchymal neoplasms of the vulvovaginal and inguinoscrotal regions are among the most diagnostically challenging specimens in the pathology laboratory owing largely to their unique intersection between general soft tissue tumors and relatively genital-specific mesenchymal tumors. Genital stromal tumors are a unique subset of soft tissue tumors encountered at this location, and this group includes fibroepithelial stromal polyp, superficial (cervicovaginal) myofibroblastoma, cellular angiofibroma, mammary-type myofibroblastoma, angiomyofibroblastoma and aggressive angiomyxoma. Aside from the striking morphologic and immunophenotypic similarity that is seen with these entities, there is evidence that a subset of genital stromal tumors may be linked genetically. This review will focus on simplifying this group of tumors and provide the pathologist or dermatopathologist with practical management information. Smooth muscle tumors of the external genitalia will also be discussed.

  1. "Ladettes," Social Representations, and Aggression.

    ERIC Educational Resources Information Center

    Muncer, Steven; Campbell, Anne; Jervis, Victoria; Lewis, Rachel

    2001-01-01

    Examined the relationship among "laddishness" (traditionally working-class, youthful, male social behavior by young women), social representations, and self-reported aggression among English college students. Measures of aggression correlated with holding more instrumental representations of aggression. Females indicated no relationship between…

  2. Children's normative beliefs about aggression and aggressive behavior.

    PubMed

    Huesmann, L R; Guerra, N G

    1997-02-01

    Normative beliefs have been defined as self-regulating beliefs about the appropriateness of social behaviors. In 2 studies the authors revised their scale for assessing normative beliefs about aggression, found that it is reliable and valid for use with elementary school children, and investigated the longitudinal relation between normative beliefs about aggression and aggressive behavior in a large sample of elementary school children living in poor urban neighborhoods. Using data obtained in 2 waves of observations 1 year apart, the authors found that children tended to approve more of aggression as they grew older and that this increase appeared to be correlated with increases in aggressive behavior. More important, although individual differences in aggressive behavior predicted subsequent differences in normative beliefs in younger children, individual differences in aggressive behavior were predicted by preceding differences in normative beliefs in older children. PMID:9107008

  3. Morphogenesis and Complexity of the Tumor Patterns

    NASA Astrophysics Data System (ADS)

    Izquierdo-Kulich, E.; Nieto-Villar, J. M.

    A mechanism to describe the apoptosis process at mesoscopic level through p53 is proposed in this paper. A deterministic model given by three differential equations is deduced from the mesoscopic approach, which exhibits sustained oscillations caused by a supercritical Andronov-Hopf bifurcation. Taking as hypothesis that the p53 sustained oscillation is the fundamental mechanism for apoptosis regulation; the model predicts that it is necessary a strict control of p53 to stimulated it, which is an important consideration to established new therapy strategy to fight cancer. The mathematical modeling of tumor growth allows us to describe the most important regularities of these systems. A stochastic model, based on the most important processes that take place at the level of individual cells, is proposed to predict the dynamical behavior of the expected radius of the tumor and its fractal dimension. It was found that the tumor has a characteristic fractal dimension, which contains the necessary information to predict the tumor growth until it reaches a stationary state. The mathematical modeling of tumor growth is an approach to explain the complex nature of these systems. A model that describes tumor growth was obtained by using a mesoscopic formalism and fractal dimension. This model theoretically predicts the relation between the morphology of the cell pattern and the mitosis/apoptosis quotient that helps to predict tumor growth from tumoral cells fractal dimension. The relation between the tumor macroscopic morphology and the cell pattern morphology is also determined. This could explain why the interface fractal dimension decreases with the increase of the cell pattern fractal dimension and consequently with the increase of the mitosis/apoptosis relation. Indexes to characterize tumoral cell proliferation and invasion capacities are proposed and used to predict the growth of different types of tumors. These indexes also show that the proliferation capacity is

  4. Tumor-induced osteomalacia. Kinetics of calcium, phosphorus, and vitamin D metabolism and characteristics of bone histomorphometry.

    PubMed

    Siris, E S; Clemens, T L; Dempster, D W; Shane, E; Segre, G V; Lindsay, R; Bilezikian, J P

    1987-02-01

    A patient with a mesenchymal tumor and hypophosphatemic osteomalacia was studied before and after tumor excision. Initial laboratory values included normal serum calcium, decreased serum phosphorus and tubular reabsorption of phosphate, undetectable 1,25-dihydroxyvitamin D, and normal parathyroid hormone. Histomorphometry of a bone biopsy specimen showed evidence of increased osteoclastic bone resorption. By 16 hours after tumor removal, 1,25-dihydroxyvitamin D level had normalized, but serum phosphorus level was unchanged; at 28 hours, both serum phosphorus value and tubular reabsorption of phosphate were within normal limits. It is concluded that tumor removal is associated with rapid correction both of 1,25-dihydroxyvitamin D production and of renal phosphate wasting. Increased bone resorption suggests the production of an osteoclast activator by the tumor and may explain the typically normal serum calcium value in this disorder. PMID:3812526

  5. Aggressive drowsy cache cells

    NASA Astrophysics Data System (ADS)

    Shawkey, H. A.; El-Dib, D. A.; Abid, Z.

    2010-01-01

    An aggressive drowsy cache block management, where the cache block is forced into drowsy mode all the time except during write and read operations, is proposed. The word line (WL) is used to enable the normal supply voltage (V DD_high) to the cache line only when it is accessed for read or write whereas the drowsy supply voltage (V DD_low) is enabled to the cache cell otherwise. The proposed block management neither needs extra cycles nor extra control signals to wake the drowsy cache cell, thereby reducing the performance penalty associated with traditional drowsy caches. In fact, the proposed aggressive drowsy mode can reduce the total power consumption of the traditional drowsy mode by 13% or even more, depending on the cache access rate, access frequency and the CMOS technology used.

  6. Aggressive papillary adenocarcinoma on atypical localization

    PubMed Central

    Balci, Mecdi Gurhan; Tayfur, Mahir; Deger, Ayse Nur; Cimen, Orhan; Eken, Huseyin

    2016-01-01

    Abstract Introduction: Aggressive digital papillary adenocarcinoma (ADPA) is a rare sweat gland tumor that is found on the fingers, toes, and the digits. To date, <100 cases have been reported in the literature. Apart from 1 case reported in the thigh, all of them were on digital or nondigital acral skin. Case presentation: A 67-year-old Caucasian woman was admitted to the hospital due to a mass on the scalp. This lesion was present for almost a year. It was a semimobile cyctic mass that elevated the scalp. There was no change in the skin color. Its dimensions were 1.5 × 1 × 0.6 cm. The laboratory, clinic, and radiologic findings (head x-ray) of the patient were normal. It was evaluated as a benign lesion such as lipoma or epidermal cyst by a surgeon due to a small semimobile mass and no erosion of the skull. It was excised by a local surgery excision. The result of the pathologic examination was aggressive papillary adenocarcinoma. This diagnosis is synonymous with ADPA. Conclusion: In our case, localization was scalp. This localization is the first for this tumor in the literature. In addition, another atypical localization of this tumor (ADPA) is thigh in the literature. This case was presented due to both the rare and atypical localizations. That is why, in our opinion, revision of “digital” term in ADPA is necessary due to seem in atypical localizations like thigh and scalp. PMID:27428196

  7. Genotypic alterations in benign and malignant salivary gland tumors: histogenetic and clinical implications.

    PubMed

    el-Naggar, A K; Hurr, K; Kagan, J; Gillenwater, A; Callender, D; Luna, M A; Batsakis, J G

    1997-06-01

    Loss of heterozygosity (LOH) and microsatellite instability (MI) were examined at 24 microsatellite loci in 46 primary benign and malignant salivary gland tumors. Among the 27 benign tumors, 11 (40.7%), manifested microsatellite alterations in at least one locus; of these, five (18.5%) showed LOH and four (14.8%) had microsatellite instability at two or more loci. Four of 11 pleomorphic adenomas (36.4%) had allele loss on the long arm of chromosome 8. Among the 19 malignant neoplasms examined, 10 (52.6%) and one (5.2%) had allele losses and MI, respectively, at multiple loci; three tumors showed MI at only one locus. Frequent LOH was detected at D8S166 (8q11-12), D17S799, and D17S122 (17p-17p11-2) loci, with an incidence of 40%, 37.5%, and 43%, respectively. In general, malignant neoplasms with LOH exhibited aggressive tumor characteristics. Statistically significant correlation's were found between LOH and pathologic classification (chi 2, p = 0.05), higher grade (p = 0.02), DNA aneuploidy (p = 0.005), and a proliferative index of > 6% (p = 0.005) of the malignant tumors. Carcinomas with 17p loci alterations, including two carcinomas expleomorphic adenoma with concurrent 8q LOH, showed more aggressive features. The results suggested that (a) loci on chromosome 8q may harbor a tumor suppressor gene or genes associated with the development or progression of some salivary neoplasms; (b) alterations on the short arm of chromosome 17 may represent an event related to tumor progression; and (c) tumors with LOH at multiple loci have aggressive biologic characteristics.

  8. A multifactorial likelihood model for MMR gene variant classification incorporating probabilities based on sequence bioinformatics and tumor characteristics: a report from the Colon Cancer Family Registry.

    PubMed

    Thompson, Bryony A; Goldgar, David E; Paterson, Carol; Clendenning, Mark; Walters, Rhiannon; Arnold, Sven; Parsons, Michael T; Michael D, Walsh; Gallinger, Steven; Haile, Robert W; Hopper, John L; Jenkins, Mark A; Lemarchand, Loic; Lindor, Noralane M; Newcomb, Polly A; Thibodeau, Stephen N; Young, Joanne P; Buchanan, Daniel D; Tavtigian, Sean V; Spurdle, Amanda B

    2013-01-01

    Mismatch repair (MMR) gene sequence variants of uncertain clinical significance are often identified in suspected Lynch syndrome families, and this constitutes a challenge for both researchers and clinicians. Multifactorial likelihood model approaches provide a quantitative measure of MMR variant pathogenicity, but first require input of likelihood ratios (LRs) for different MMR variation-associated characteristics from appropriate, well-characterized reference datasets. Microsatellite instability (MSI) and somatic BRAF tumor data for unselected colorectal cancer probands of known pathogenic variant status were used to derive LRs for tumor characteristics using the Colon Cancer Family Registry (CFR) resource. These tumor LRs were combined with variant segregation within families, and estimates of prior probability of pathogenicity based on sequence conservation and position, to analyze 44 unclassified variants identified initially in Australasian Colon CFR families. In addition, in vitro splicing analyses were conducted on the subset of variants based on bioinformatic splicing predictions. The LR in favor of pathogenicity was estimated to be ~12-fold for a colorectal tumor with a BRAF mutation-negative MSI-H phenotype. For 31 of the 44 variants, the posterior probabilities of pathogenicity were such that altered clinical management would be indicated. Our findings provide a working multifactorial likelihood model for classification that carefully considers mode of ascertainment for gene testing.

  9. Spontaneous squamous cell carcinoma induced by the somatic inactivation of retinoblastoma and Trp53 tumor suppressors.

    PubMed

    Martínez-Cruz, Ana Belén; Santos, Mirentxu; Lara, M Fernanda; Segrelles, Carmen; Ruiz, Sergio; Moral, Marta; Lorz, Corina; García-Escudero, Ramón; Paramio, Jesús M

    2008-02-01

    Squamous cell carcinomas (SCC) represent the most aggressive type of nonmelanoma skin cancer. Although little is known about the causal alterations of SCCs, in organ-transplanted patients the E7 and E6 oncogenes of human papillomavirus, targeting the p53- and pRb-dependent pathways, have been widely involved. Here, we report the functional consequences of the simultaneous elimination of Trp53 and retinoblastoma (Rb) genes in epidermis using Cre-loxP system. Loss of p53, but not pRb, produces spontaneous tumor development, indicating that p53 is the predominant tumor suppressor acting in mouse epidermis. Although the simultaneous inactivation of pRb and p53 does not aggravate the phenotype observed in Rb-deficient epidermis in terms of proliferation and/or differentiation, spontaneous SCC development is severely accelerated in doubly deficient mice. The tumors are aggressive and undifferentiated and display a hair follicle origin. Detailed analysis indicates that the acceleration is mediated by premature activation of the epidermal growth factor receptor/Akt pathway, resulting in increased proliferation in normal and dysplastic hair follicles and augmented tumor angiogenesis. The molecular characteristics of this model provide valuable tools to understand epidermal tumor formation and may ultimately contribute to the development of therapies for the treatment of aggressive squamous cancer. PMID:18245467

  10. Molecular subtype and tumor characteristics of breast cancer metastases as assessed by gene expression significantly influence patient post-relapse survival

    PubMed Central

    Tobin, N. P.; Harrell, J. C.; Lövrot, J.; Egyhazi Brage, S.; Frostvik Stolt, M.; Carlsson, L.; Einbeigi, Z.; Linderholm, B.; Loman, N.; Malmberg, M.; Walz, T.; Fernö, M.; Perou, C. M.; Bergh, J.; Hatschek, T.; Lindström, L. S.; Hatschek, Thomas; Fernö, Mårten; Lindström, Linda Sofie; Hedenfalk, Ingrid; Brandberg, Yvonne; Carstensen, John; Egyhazy, Suzanne; Stolt, Marianne Frostvik; Skoog, Lambert; Hellström, Mats; Maliniemi, Maarit; Svensson, Helene; Åström, Gunnar; Bergh, Jonas; Bjöhle, Judith; Lidbrink, Elisabet; Rotstein, Sam; Wallberg, Birgitta; Einbeigi, Zakaria; Carlsson, Per; Linderholm, Barbro; Walz, Thomas; Loman, Niklas; Malmström, Per; Söderberg, Martin; Malmberg, Martin; Carlsson, Lena; Umeå; Lindh, Birgitta; Sundqvist, Marie; Malmberg, Lena

    2015-01-01

    Background We and others have recently shown that tumor characteristics are altered throughout tumor progression. These findings emphasize the need for re-examination of tumor characteristics at relapse and have led to recommendations from ESMO and the Swedish Breast Cancer group. Here, we aim to determine whether tumor characteristics and molecular subtypes in breast cancer metastases confer clinically relevant prognostic information for patients. Patients and methods The translational aspect of the Swedish multicenter randomized trial called TEX included 111 patients with at least one biopsy from a morphologically confirmed locoregional or distant breast cancer metastasis diagnosed from December 2002 until June 2007. All patients had detailed clinical information, complete follow-up, and metastasis gene expression information (Affymetrix array GPL10379). We assessed the previously published gene expression modules describing biological processes [proliferation, apoptosis, human epidermal receptor 2 (HER2) and estrogen (ER) signaling, tumor invasion, immune response, and angiogenesis] and pathways (Ras, MAPK, PTEN, AKT-MTOR, PI3KCA, IGF1, Src, Myc, E2F3, and β-catenin) and the intrinsic subtypes (PAM50). Furthermore, by contrasting genes expressed in the metastases in relation to survival, we derived a poor metastasis survival signature. Results A significant reduction in post-relapse breast cancer-specific survival was associated with low-ER receptor signaling and apoptosis gene module scores, and high AKT-MTOR, Ras, and β-catenin module scores. Similarly, intrinsic subtyping of the metastases provided statistically significant post-relapse survival information with the worst survival outcome in the basal-like [hazard ratio (HR) 3.7; 95% confidence interval (CI) 1.3–10.9] and HER2-enriched (HR 4.4; 95% CI 1.5–12.8) subtypes compared with the luminal A subtype. Overall, 25% of the metastases were basal-like, 32% HER2-enriched, 10% luminal A, 28% luminal B

  11. Targeted immunotherapy for pediatric solid tumors

    PubMed Central

    Kopp, Lisa M.; Katsanis, Emmanuel

    2016-01-01

    ABSTRACT Metastatic and refractory pediatric solid tumor malignancies continue to have a poor outcome despite the > 80% cure rates appreciated in many pediatric cancers. Targeted immunotherapy is impacting treatment and survival in these aggressive tumors. We review current promising immunotherapeutic approaches in the pediatric oncology solid tumor setting. PMID:27141344

  12. Crossing the barrier: treatment of brain tumors using nanochain particles.

    PubMed

    Karathanasis, Efstathios; Ghaghada, Ketan B

    2016-09-01

    Despite advancements in surgery and radiotherapy, the aggressive forms of brain tumors, such as gliomas, are still uniformly lethal with current therapies offering only palliation complicated by significant toxicities. Gliomas are characteristically diffuse with infiltrating edges, resistant to drugs and nearly inaccessible to systemic therapies due to the brain-tumor barrier. Currently, aggressive efforts are underway to further understand brain-tumor's microenvironment and identify brain tumor cell-specific regulators amenable to pharmacologic interventions. While new potent agents are continuously becoming available, efficient drug delivery to brain tumors remains a limiting factor. To tackle the drug delivery issues, a multicomponent chain-like nanoparticle has been developed. These nanochains are comprised of iron oxide nanospheres and a drug-loaded liposome chemically linked into a 100-nm linear, chain-like assembly with high precision. The nanochain possesses a unique ability to scavenge the tumor endothelium. By utilizing effective vascular targeting, the nanochains achieve rapid deposition on the vascular bed of glioma sites establishing well-distributed drug reservoirs on the endothelium of brain tumors. After reaching the target sites, an on-command, external low-power radiofrequency field can remotely trigger rapid drug release, due to mechanical disruption of the liposome, facilitating widespread and effective drug delivery into regions harboring brain tumor cells. Integration of the nanochain delivery system with the appropriate combination of complementary drugs has the potential to unfold the field and allow significant expansion of therapies for the disease where success is currently very limited. WIREs Nanomed Nanobiotechnol 2016, 8:678-695. doi: 10.1002/wnan.1387 For further resources related to this article, please visit the WIREs website.

  13. Preliminary study on the automated detection of breast tumors using the characteristic features from unenhanced MR images

    NASA Astrophysics Data System (ADS)

    Adachi, Hayato; Teramoto, Atsushi; Miyajo, Satomi; Yamamuro, Osamu; Ohmi, Kumiko; Nishio, Masami; Fujita, Hiroshi

    2015-03-01

    Breast cancer incidence tends to rise globally and the mortality rate for breast cancer is increasing in Japan. There are various screening modalities for breast cancer, and MRI examinations with high detection rate are used for high-risk groups, which are genetically prone to develop breast cancer. In the breast MRI examination, unenhanced T1 and T2 weighted images shows no significant difference in signal value between tumor and normal tissue. Therefore, tumors are identified with use of contrast enhanced kinetic curve obtained by dynamic scan using contrast agent. Some computer aided diagnosis methods using dynamic contrast enhanced MR images also have been proposed. However, contrast agent produces the allergic reaction in rare case; it should not be used for screening examinees. Here, MRI provides the anatomical and functional information by using various sequences without contrast agents. According to the reports, this information can discriminate between tumor and normal tissue. In this study, we analyzed unenhanced MR images by using plural sequences and developed an automated method for the detection of tumors. First, we extracted the breast region from the T1-weighted image semi-automatically. Next, using the threshold determined by considering the signal intensities of tumor and normal tissue, a thresholding method was applied for diffusion-weighted image to extract the first candidate regions. After labeling processing, the breast region removes outside candidates from Initial candidates. Then false positives are reduced by the rule-based classifier. Finally, we examined the remaining candidates as possible tumor regions. We applied the proposed method to 54 cases of MR images and evaluated its usefulness. As a result, the detection sensitivity was 71.9% and the abnormal regions were clearly detected. These results indicate that the proposed method may be useful for tumor detection in unenhanced breast MR images.

  14. Girls, aggression, and emotion regulation.

    PubMed

    Conway, Anne M

    2005-04-01

    Many studies have demonstrated that boys are more aggressive than girls (see J. D. Coie & K. Dodge, 1997, for a review) and that emotion regulation difficulties are associated with problematic behaviors (N. Eisenberg & R. A. Fabes, 1999; M. Gilliom, D. S. Shaw, J. E. Beck, M. A. Schonberg, & J. L. Lukon, 2002). However, recent findings indicate that gender differences in aggressive behaviors disappear when assessments are broadened to include relational aggression--behaviors designed to harm the relationship goals of others by spreading rumors, gossiping, and eliciting peer rejection of others. Moreover, although difficulties regulating emotions have been reported for physically aggressive children, little research has examined these processes in relationally aggressive children. This article argues that investigation into the associations between emotion regulation and relational aggression is a critical direction for future research on the etiology and prevention of mental health problems in girls. PMID:15839769

  15. [The aggressive child (author's transl)].

    PubMed

    Harbauer, H

    1978-08-01

    In children a "normal" aggressiveness should be distinguished from "hostile" and "inhibited" aggression; the latter usually become apparent as heteroaggressive or autoaggressive behaviour. Autoaggression is more common with younger children. Different hypotheses about the origin of aggressiveness are discussed. In the younger child nail biting, trichotillomania, rocking, an intensified phase of contrariness and enkopresis may have components of aggressiveness. In older children and adolescents dissocial forms of development, drug taking, attempted suicid, and anorexia nervosa may be parts of aggressive behaviour. Minimal brain dysfunction, autism, and postencephalitic syndromes predominate amongst organic alterations of the brain as causes for aggressive behaviour. Particularly the Lesch-Nyhan-syndrome, but equally the Cornelia de Lange-syndrome show autoaggressive tendencies.

  16. Mucoepidermoid tumors of the lung.

    PubMed

    Yousem, S A; Hochholzer, L

    1987-09-15

    Mucoepidermoid tumors of lung (MET) are rare tumors derived from the minor salivary gland tissue of the proximal tracheobronchial tree. The authors studied 58 cases of MET confined to the lung and used criteria derived from similar tumors of the salivary glands to separate them into low-grade and high-grade variants. The overwhelming majority of low-grade tumors behaved in a benign fashion, whereas 23% of high-grade tumors resulted in patient death. Prognostic factors which appeared to predict future aggressive behavior included high-grade classification, advanced stage at presentation, and perhaps lymph node metastases.

  17. Pediatric Fibroblastic and Myofibroblastic Tumors: A Pictorial Review.

    PubMed

    Sargar, Kiran M; Sheybani, Elizabeth F; Shenoy, Archana; Aranake-Chrisinger, John; Khanna, Geetika

    2016-01-01

    Pediatric fibroblastic and myofibroblastic tumors are a relatively common group of soft-tissue proliferations that are associated with a wide spectrum of clinical behavior. These tumors have been divided into the following categories on the basis of their biologic behavior: benign (eg, myositis ossificans, myofibroma, fibromatosis colli), intermediate-locally aggressive (eg, lipofibromatosis, desmoid fibroma), intermediate-rarely metastasizing (eg, inflammatory myofibroblastic tumors, infantile fibrosarcoma, low-grade myofibroblastic sarcoma), and malignant (eg, fibromyxoid sarcoma, adult fibrosarcoma). Imaging has a key role in the evaluation of lesion origin, extent, and involvement with adjacent structures, and in the treatment management and postresection surveillance of these tumors. The imaging findings of these tumors are often nonspecific. However, certain imaging features, such as low or intermediate signal intensity on T2-weighted magnetic resonance images and extension along fascial planes, support the diagnosis of a fibroblastic or myofibroblastic tumor. In addition, certain tumors have characteristic imaging findings (eg, multiple subcutaneous or intramuscular lesions in infantile myofibromatosis, plaquelike growth pattern of Gardner fibroma, presence of adipose tissue in lipofibromatosis) or characteristic clinical manifestations (eg, great toe malformations in fibrodysplasia ossificans fibroma, neonatal torticollis in fibromatosis colli) that suggest the correct diagnosis. Knowledge of the syndrome associations of some of these tumors-for example, the association between familial adenomatous polyposis syndrome and both Gardner fibroma and desmoid fibromatosis, and that between nevoid basal cell carcinoma syndrome and cardiac fibroma-further facilitate a diagnosis. The recognition of key imaging findings can help guide treatment management and help avoid unnecessary intervention in cases of benign lesions such as myositis ossificans and fibromatosis

  18. Novel Treatment Shrinks Ovarian Tumors in Mice

    Cancer.gov

    Researchers have developed a new approach for treating tumors that express mutant versions of the p53 protein, which are present in more than half of all cancers, including an aggressive and common subtype of ovarian cancer.

  19. Rethinking Aggression: A Typological Examination of the Functions of Aggression.

    ERIC Educational Resources Information Center

    Little, Todd D.; Brauner, Jessica; Jones, Stephanie M.; Nock, Matthew K.; Hawley, Patricia H.

    2003-01-01

    Compared five subgroups of aggressive children and adolescents on several adjustment correlates. Found that the reactive group and the group high on both instrumental and reactive reasons for aggression showed consistent maladaptive patterns across the adjustment correlates. The instrumental and typical groups (moderate on instrumental and…

  20. THE IMPACT OF AGGRESSION IN THE CLASSROOM.

    ERIC Educational Resources Information Center

    MCNEIL, ELTON B.; AND OTHERS

    IN THIS INVESTIGATION, AGGRESSION WAS MEASURED FROM FOUR PERSPECTIVES--(1) THE PERCEPTION THAT THE SUBJECT HAD OF HIS AGGRESSION, (2) HIS SATISFACTION, AS HE VIEWED IT, WITH HIS OWN AGGRESSION, (3) THE PERCEPTION THAT THE TEACHER HAD OF THE SUBJECT'S AGGRESSIVENESS, AND (4) THE PERCEPTION OF THE SUBJECT'S AGGRESSIVENESS HELD BY HIS CLASSMATES. IN…

  1. The Effects of Pornography on Aggressive Behavior.

    ERIC Educational Resources Information Center

    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…

  2. Characteristics of tissue distribution of various polysaccharides as drug carriers: influences of molecular weight and anionic charge on tumor targeting.

    PubMed

    Sugahara, S; Okuno, S; Yano, T; Hamana, H; Inoue, K

    2001-05-01

    Using the Walker 256 model for carcinosarcoma-bearing rats, we intravenously administered 5 polysaccharide carriers with various molecular weights (MWs) and electric charges and tested for their plasma and tissue distribution. Two carriers, carboxymethylated-D-manno-D-glucan (CMMG) and CMdextran (CMDex), showed higher plasma AUC than the other carriers tested, namely, CMchitin (CMCh), N-desulfated N-acetylated heparin (DSH), and hyaluronic acid (HA). This was consistently found to be true over the range of MWs tested. For CMDex, the maximum value of plasma AUC was obtained when the MW exceeded 150 kDa. As for the anionic charge, CMDex (110-180 kDa) with a degree of substitution (DS) of the CM groups ranging from 0.2 to 0.6, showed maximum plasma AUC values. Twenty-four hours after administration, the concentration of CMDex (180-250 kDa; DS: 0.6-1.2) in tumors was more than 3% of dose/g--approximately 10-fold higher than those observed with CMCh, DSH and HA. Doxorubicin (DXR) was bound to these carriers via a peptide spacer, GlyGlyPheGly (GGFG), to give carrier-GGFG-DXR conjugates (DXR content: 4.2-7.0 (w/w)%), and the antitumor effects of these conjugates were tested with Walker 256 carcinosarcoma-bearing rats by monitoring the tumor weights after a single intravenous injection. Compared with free DXR, CMDex-GGFG-DXR and CMMG-GGFG-DXR conjugates significantly suppressed tumor growth, while the CMCh-GGFG-DXR, DSH-GGFG-DXR, and HA-GGFG-DXR conjugates in a similar comparison showed weak tumor growth inhibition. These findings suggest that the antitumor effect of the carrier-DXR conjugates was related to the extent with which the carriers accumulated in the tumors.

  3. The relationship between cultural individualism-collectivism and student aggression across 62 countries.

    PubMed

    Bergmüller, Silvia

    2013-01-01

    This study examined the relationship between countries' dominant cultural values (i.e., individualism and collectivism) and (a) school principals' perceptions of aggressive student behavior and (b) students' self-reports of being aggressively victimized in school. Data on student aggression and victimization were collected across 62 countries in nationally representative samples of fourth and eighth graders (N = 428,566) and their principals (N = 15,043) by the Trends in International Mathematics and Science Study (TIMSS) 2007. Students were asked about three forms of aggressive victimization: physical, verbal, and relational; principals about two forms of aggressive student behavior: physical and verbal. Country-level regression analyses revealed that the level of cultural individualism, according to the individualism index (IDV) by Hofstede, Hofstede, and Minkov (2010), was not significantly related to either form of student-reported victimization. However, school principals reported aggressive student behavior more often the more individualist, and hence less collectivist, their country's culture. This relation was evident in the principals' reports on 4th and 8th grade students' aggressive behavior for both physical and verbal aggression. Multilevel analyses revealed that cultural individualism was still a powerful predictor of principal-reported aggressive student behavior after controlling for school and country characteristics. The discussion outlines reasons why principals' reports of aggressive student behavior are probably more valid indicators of student aggression than student self-reports of victimization, thereby supporting the hypothesis of culture-dependency of aggression. PMID:23494751

  4. Hormone-dependent aggression in male and female rats: experiential, hormonal, and neural foundations.

    PubMed

    Albert, D J; Jonik, R H; Walsh, M L

    1992-01-01

    Hormone-dependent aggression in both male and female rats includes the distinctive behavioral characteristics of piloerection and lateral attack. In males the aggression is dependent on testicular testosterone and is commonly known as intermale aggression. In females, the aggression is most commonly observed as maternal aggression and is dependent on hormones whose identity is only beginning to emerge. The present review examines the experiential events which activate hormone-dependent aggression, the relation of the aggression to gonadal hormones, and the neural structures that participate in its modulation. In males and females, the aggression is activated by cohabitation with a conspecific of the opposite sex, by competitive experience, and by repeated exposure to unfamiliar conspecifics. In the female, the presence of pups also activates aggression. In both males and females, hormones are necessary for the full manifestation of the aggression. The essential hormone appears to be testosterone in males and a combination of testosterone and estradiol in females. The information available suggests the neural control systems for hormone-dependent aggression may be similar in males and females. It is argued that hormone-dependent aggression is behaviorally and biologically homologous in male and female rats.

  5. The relationship between cultural individualism-collectivism and student aggression across 62 countries.

    PubMed

    Bergmüller, Silvia

    2013-01-01

    This study examined the relationship between countries' dominant cultural values (i.e., individualism and collectivism) and (a) school principals' perceptions of aggressive student behavior and (b) students' self-reports of being aggressively victimized in school. Data on student aggression and victimization were collected across 62 countries in nationally representative samples of fourth and eighth graders (N = 428,566) and their principals (N = 15,043) by the Trends in International Mathematics and Science Study (TIMSS) 2007. Students were asked about three forms of aggressive victimization: physical, verbal, and relational; principals about two forms of aggressive student behavior: physical and verbal. Country-level regression analyses revealed that the level of cultural individualism, according to the individualism index (IDV) by Hofstede, Hofstede, and Minkov (2010), was not significantly related to either form of student-reported victimization. However, school principals reported aggressive student behavior more often the more individualist, and hence less collectivist, their country's culture. This relation was evident in the principals' reports on 4th and 8th grade students' aggressive behavior for both physical and verbal aggression. Multilevel analyses revealed that cultural individualism was still a powerful predictor of principal-reported aggressive student behavior after controlling for school and country characteristics. The discussion outlines reasons why principals' reports of aggressive student behavior are probably more valid indicators of student aggression than student self-reports of victimization, thereby supporting the hypothesis of culture-dependency of aggression.

  6. Multiple keratocystic odontogenic tumors in nevoid basal cell carcinoma syndrome

    PubMed Central

    Pereira, Treville; Tamgadge, Avinash; Sapdhare, Swati; Pujar, Ashwini

    2015-01-01

    Keratocystic odontogenic tumor (KCOT) is of particular interest because its recurrence rate is high and its behavior is aggressive. Nevoid basal cell carcinoma syndrome (NBCCS), which is also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and with a predisposition to neoplasms. These multiple KCOTs have warranted an aggressive treatment at the earliest because of the damage and possible complications. Recurrence of these lesions is a characteristic feature that has to be considered while explaining the prognosis to the patient. Here, we report a case of a 14-year-old boy with clinical features of basal cell nevus syndrome and multiple KCOTs. In addition to the other common features, congenitally missing third molars in all the four quadrants is a feature which has not been previously reported in association with NBCCS in Indian patients. PMID:26981489

  7. Psychological Research on Human Aggressiveness

    ERIC Educational Resources Information Center

    Hamburg, D. A.; Brodie, H. K. H.

    1973-01-01

    Discusses research relating to the effects of hormones, neurophysiology, and the environment on animal and human aggression. Indicates that the interactions of biological, psychological and social processes in the development of human aggressiveness should constitute one of the principal frontiers for science in the next two decades. (JR)

  8. Aggression and Violence in Youth.

    ERIC Educational Resources Information Center

    William Gladden Foundation, York, PA.

    This booklet was written to provide an understanding of aggression and violence in youth. Its purpose is to help parents, professionals, and other concerned citizens prevent or reduce these potentially dangerous behaviors. The introduction notes that many experts agree that aggression and violence are on the rise in America. The first section of…

  9. Instrumental and Social Outcome Expectations of High-Aggressive and Low-Aggressive Boys.

    ERIC Educational Resources Information Center

    Cillessen, Antonius H. N.; Hubbard, Julie A.

    This study examined high-aggressive and low-aggressive boys' ratings of the effectiveness of aggressive and assertive strategies for solving social problems involving hypothetical peers and actual peers. Subjects were 66 third-grade boys (11 groups of 6 boys each for a total of 22 high-aggressive, 22 low-aggressive, and 22 average aggressive boys)…

  10. Contrast-enhanced radiotherapy: feasibility and characteristics of the physical absorbed dose distribution for deep-seated tumors

    NASA Astrophysics Data System (ADS)

    Garnica-Garza, H. M.

    2009-09-01

    Radiotherapy using kilovoltage x-rays in conjunction with contrast agents incorporated into the tumor, gold nanoparticles in particular, could represent a potential alternative to current techniques based on high-energy linear accelerators. In this paper, using the voxelized Zubal phantom in conjunction with the Monte Carlo code PENELOPE to model a prostate cancer treatment, it is shown that in combination with a 360° arc delivery technique, tumoricidal doses of radiation can be delivered to deep-seated tumors while still providing acceptable doses to the skin and other organs at risk for gold concentrations in the tumor within the range of 7-10 mg-Au per gram of tissue. Under these conditions and using a x-ray beam with 90% of the fluence within the range of 80-200 keV, a 72 Gy physical absorbed dose to the prostate can be delivered, while keeping the rectal wall, bladder, skin and femoral heads below 65 Gy, 55 Gy, 40 Gy and 30 Gy, respectively. However, it is also shown that non-uniformities in the contrast agent concentration lead to a severe degradation of the dose distribution and that, therefore, techniques to locally quantify the presence of the contrast agent would be necessary in order to determine the incident x-ray fluence that best reproduces the dosimetry obtained under conditions of uniform contrast agent distribution.

  11. Contrast-enhanced radiotherapy: feasibility and characteristics of the physical absorbed dose distribution for deep-seated tumors.

    PubMed

    Garnica-Garza, H M

    2009-09-21

    Radiotherapy using kilovoltage x-rays in conjunction with contrast agents incorporated into the tumor, gold nanoparticles in particular, could represent a potential alternative to current techniques based on high-energy linear accelerators. In this paper, using the voxelized Zubal phantom in conjunction with the Monte Carlo code PENELOPE to model a prostate cancer treatment, it is shown that in combination with a 360 degrees arc delivery technique, tumoricidal doses of radiation can be delivered to deep-seated tumors while still providing acceptable doses to the skin and other organs at risk for gold concentrations in the tumor within the range of 7-10 mg-Au per gram of tissue. Under these conditions and using a x-ray beam with 90% of the fluence within the range of 80-200 keV, a 72 Gy physical absorbed dose to the prostate can be delivered, while keeping the rectal wall, bladder, skin and femoral heads below 65 Gy, 55 Gy, 40 Gy and 30 Gy, respectively. However, it is also shown that non-uniformities in the contrast agent concentration lead to a severe degradation of the dose distribution and that, therefore, techniques to locally quantify the presence of the contrast agent would be necessary in order to determine the incident x-ray fluence that best reproduces the dosimetry obtained under conditions of uniform contrast agent distribution.

  12. Measurement of Cancer Cell Growth Heterogeneity through Lentiviral Barcoding Identifies Clonal Dominance as a Characteristic of In Vivo Tumor Engraftment.

    PubMed

    Nolan-Stevaux, Olivier; Tedesco, Donato; Ragan, Seamus; Makhanov, Mikhail; Chenchik, Alex; Ruefli-Brasse, Astrid; Quon, Kim; Kassner, Paul D

    2013-01-01

    Advances in the fields of cancer initiating cells and high-throughput in vivo shRNA screens have highlighted a need to observe the growth of tumor cells in cancer models at the clonal level. While in vivo cancer cell growth heterogeneity in xenografts has been described, it has yet to be measured. Here, we tested an approach to quantify the clonal growth heterogeneity of cancer cells in subcutaneous xenograft mouse models. Using a high-throughput sequencing method, we followed the fate in vitro and in vivo of ten thousand HCT-116 cells individually tagged with a unique barcode delivered by lentiviral transduction. While growth in vitro was less homogeneous than anticipated, we still find that 95% of the final cells derived from 80% of the original cells. In xenografts, however, 95% of the retrieved barcoded cells originated from only 6% of the initially injected cells, an effect we term "clonal dominance". We observed this clonal dominance in two additional xenograft models (MDA-MB-468 and A2780(cis)) and in two different host strains (NSG and Nude). By precisely and reproducibly quantifying clonal cancer cell growth in vivo, we find that a small subset of clones accounts for the vast majority of the descendant cells, even with HCT-116, a cell line reported to lack a tumor-initiating compartment. The stochastic in vivo selection process we describe has important implications for the fields of in vivo shRNA screening and tumor initiating cells.

  13. Aggressive Erotica and Violence against Women.

    ERIC Educational Resources Information Center

    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)

  14. Involvement in internet aggression during early adolescence.

    PubMed

    Werner, Nicole E; Bumpus, Matthew F; Rock, Daquarii

    2010-06-01

    The current study examined concurrent and longitudinal predictors of early adolescents' involvement in Internet aggression. Cross-sectional results (N = 330; 57% female) showed that the likelihood of reporting Internet aggression was higher among youth who spent more time using Internet-based technologies to communicate with friends and who were themselves targets of Internet aggression. Offline relational aggression and beliefs supportive of relational and physical aggression also predicted concurrent involvement in Internet aggression. We used longitudinal data (N = 150; 51% female) to distinguish between youth who were aggressive in traditional contexts only (i.e., school) from those who were aggressive both online and offline. These results indicated that youth who were aggressive both online and offline were older at the initial assessment, were targets of Internet aggression, and held beliefs more supportive of relational aggression than youth who were aggressive offline only. Implications and directions for future research are discussed.

  15. Tachykinin-expressing neurons control male-specific aggressive arousal in Drosophila.

    PubMed

    Asahina, Kenta; Watanabe, Kiichi; Duistermars, Brian J; Hoopfer, Eric; González, Carlos Roberto; Eyjólfsdóttir, Eyrún Arna; Perona, Pietro; Anderson, David J

    2014-01-16

    Males of most species are more aggressive than females, but the neural mechanisms underlying this dimorphism are not clear. Here, we identify a neuron and a gene that control the higher level of aggression characteristic of Drosophila melanogaster males. Males, but not females, contain a small cluster of FruM(+) neurons that express the neuropeptide tachykinin (Tk). Activation and silencing of these neurons increased and decreased, respectively, intermale aggression without affecting male-female courtship behavior. Mutations in both Tk and a candidate receptor, Takr86C, suppressed the effect of neuronal activation, whereas overexpression of Tk potentiated it. Tk neuron activation overcame reduced aggressiveness caused by eliminating a variety of sensory or contextual cues, suggesting that it promotes aggressive arousal or motivation. Tachykinin/Substance P has been implicated in aggression in mammals, including humans. Thus, the higher aggressiveness of Drosophila males reflects the sexually dimorphic expression of a neuropeptide that controls agonistic behaviors across phylogeny. PMID:24439378

  16. Novel Therapies for Aggressive B-Cell Lymphoma

    PubMed Central

    Foon, Kenneth A.; Takeshita, Kenichi; Zinzani, Pier L.

    2012-01-01

    Aggressive B-cell lymphoma (BCL) comprises a heterogeneous group of malignancies, including diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, and mantle cell lymphoma (MCL). DLBCL, with its 3 subtypes, is the most common type of lymphoma. Advances in chemoimmunotherapy have substantially improved disease control. However, depending on the subtype, patients with DLBCL still exhibit substantially different survival rates. In MCL, a mature B-cell lymphoma, the addition of rituximab to conventional chemotherapy regimens has increased response rates, but not survival. Burkitt lymphoma, the most aggressive BCL, is characterized by a high proliferative index and requires more intensive chemotherapy regimens than DLBCL. Hence, there is a need for more effective therapies for all three diseases. Increased understanding of the molecular features of aggressive BCL has led to the development of a range of novel therapies, many of which target the tumor in a tailored manner and are summarized in this paper. PMID:22536253

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

    PubMed Central

    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

  18. Eribulin mesylate reduces tumor microenvironment abnormality by vascular remodeling in preclinical human breast cancer models

    PubMed Central

    Funahashi, Yasuhiro; Okamoto, Kiyoshi; Adachi, Yusuke; Semba, Taro; Uesugi, Mai; Ozawa, Yoichi; Tohyama, Osamu; Uehara, Taisuke; Kimura, Takayuki; Watanabe, Hideki; Asano, Makoto; Kawano, Satoshi; Tizon, Xavier; McCracken, Paul J; Matsui, Junji; Aoshima, Ken; Nomoto, Kenichi; Oda, Yoshiya

    2014-01-01

    Eribulin mesylate is a synthetic macrocyclic ketone analog of the marine sponge natural product halichondrin B and an inhibitor of microtubule dynamics. Some tubulin-binding drugs are known to have antivascular (antiangiogenesis or vascular-disrupting) activities that can target abnormal tumor vessels. Using dynamic contrast-enhanced MRI analyses, here we show that eribulin induces remodeling of tumor vasculature through a novel antivascular activity in MX-1 and MDA-MB-231 human breast cancer xenograft models. Vascular remodeling associated with improved perfusion was shown by Hoechst 33342 staining and by increased microvessel density together with decreased mean vascular areas and fewer branched vessels in tumor tissues, as determined by immunohistochemical staining for endothelial marker CD31. Quantitative RT-PCR analysis of normal host cells in the stroma of xenograft tumors showed that eribulin altered the expression of mouse (host) genes in angiogenesis signaling pathways controlling endothelial cell–pericyte interactions, and in the epithelial–mesenchymal transition pathway in the context of the tumor microenvironment. Eribulin also decreased hypoxia-associated protein expression of mouse (host) vascular endothelial growth factor by ELISA and human CA9 by immunohistochemical analysis. Prior treatment with eribulin enhanced the anti-tumor activity of capecitabine in the MDA-MB-231 xenograft model. These findings suggest that eribulin-induced remodeling of abnormal tumor vasculature leads to a more functional microenvironment that may reduce the aggressiveness of tumors due to elimination of inner tumor hypoxia. Because abnormal tumor microenvironments enhance both drug resistance and metastasis, the apparent ability of eribulin to reverse these aggressive characteristics may contribute to its clinical benefits. PMID:25060424

  19. IGF-1R inhibition in mammary epithelia promotes canonical Wnt signaling and Wnt1-driven tumors

    PubMed Central

    Rota, Lauren M.; Albanito, Lidia; Shin, Marcus E.; Goyeneche, Corey L.; Shushanov, Sain; Gallagher, Emily J.; LeRoith, Derek; Lazzarino, Deborah A.; Wood, Teresa L.

    2014-01-01

    Triple-negative breast cancers (TNBC) are an aggressive disease subtype which unlike other subtypes lack an effective targeted therapy. Inhibitors of the insullin-like growth factor receptor (IGF-1R) have been considered for use in treating TNBC. Here we provide genetic evidence that IGF-1R inhibition promotes development of Wnt1-mediated murine mammary tumors that offer a model of TNBC. We found that in a double transgenic mouse model carrying activated Wnt-1 and mutant IGF-1R, a reduction in IGF-1R signaling reduced tumor latency and promoted more aggressive phenotypes. These tumors displayed a squamal cell phenotype with increased expression of keratins 5/6 and β-catenin. Notably, cell lineage analyses revealed an increase in basal (CD29hi/CD24+) and luminal (CD24+/CD61+/CD29lo) progenitor cell populations, along with increased Nanog expression and decreased Elf5 expression. In these doubly transgenic mice, lung metastases developed with characteristics of the primary tumors, unlike MMTV-Wnt1 mice. Mechanistic investigations showed that pharmacological inhibition of the IGF-1R in vitro was sufficient to increase the tumorsphere-forming efficiency of MMTV-Wnt1 tumor cells. Tumors from doubly transgenic mice also exhibited an increase in the expression ratio of the IGF-II-sensitive, A isoform of the insulin receptor vs the IR-B isoform, which in vitro resulted in enhanced expression of β-catenin. Overall, our results revealed that in Wnt-driven tumors an attenuation of IGF-1R signaling accelerates tumorigenesis and promotes more aggressive phenotypes, with potential implications for understanding TNBC pathobiology and treatment. PMID:25092896

  20. Src: Marker or Actor in Prostate Cancer Aggressiveness

    PubMed Central

    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. PMID:25184116

  1. Predicting workplace aggression and violence.

    PubMed

    Barling, Julian; Dupré, Kathryne E; Kelloway, E Kevin

    2009-01-01

    Consistent with the relative recency of research on workplace aggression and the considerable media attention given to high-profile incidents, numerous myths about the nature of workplace aggression have emerged. In this review, we examine these myths from an evidence-based perspective, bringing greater clarity to our understanding of the predictors of workplace aggression. We conclude by pointing to the need for more research focusing on construct validity and prevention issues as well as for methodologies that minimize the likelihood of mono-method bias and that strengthen the ability to make causal inferences.

  2. Screening outcomes in older US women undergoing multiple mammograms in community practice: does interval, age, or comorbidity score affect tumor characteristics or false positive rates?

    PubMed

    Braithwaite, Dejana; Zhu, Weiwei; Hubbard, Rebecca A; O'Meara, Ellen S; Miglioretti, Diana L; Geller, Berta; Dittus, Kim; Moore, Dan; Wernli, Karen J; Mandelblatt, Jeanne; Kerlikowske, Karla

    2013-03-01

    Background Uncertainty exists about the appropriate use of screening mammography among older women because comorbid illnesses may diminish the benefit of screening. We examined the risk of adverse tumor characteristics and false positive rates according to screening interval, age, and comorbidity. Methods From January 1999 to December 2006, data were collected prospectively on 2993 older women with breast cancer and 137 949 older women without breast cancer who underwent mammography at facilities that participated in a data linkage between the Breast Cancer Surveillance Consortium and Medicare claims. Women were aged 66 to 89 years at study entry to allow for measurement of 1 year of preexisting illnesses. We used logistic regression analyses to calculate the odds of advanced (IIb, III, IV) stage, large (>20 millimeters) tumors, and 10-year cumulative probability of false-positive mammography by screening frequency (1 vs 2 years), age, and comorbidity score. The comorbidity score was derived using the Klabunde approximation of the Charlson score. All statistical tests were two-sided. Results Adverse tumor characteristics did not differ statistically significantly by comorbidity, age, or interval. Cumulative probability of a false-positive mammography result was higher among annual screeners than biennial screeners irrespective of comorbidity: 48.0% (95% confidence interval [CI] = 46.1% to 49.9%) of annual screeners aged 66 to 74 years had a false-positive result compared with 29.0% (95% CI = 28.1% to 29.9%) of biennial screeners. Conclusion Women aged 66 to 89 years who undergo biennial screening mammography have similar risk of advanced-stage disease and lower cumulative risk of a false-positive recommendation than annual screeners, regardless of comorbidity.

  3. Characteristics of the accumulation of methotrexate polyglutamate derivatives in Ehrlich ascites tumor cells and isolated rat hepatocytes

    SciTech Connect

    Fry, D.W.; Gewirtz, D.A.; Yalowich, J.C.; Goldman, I.D.

    1983-01-01

    The intracellular synthesis and retention of polygammaglutamyl derivatives of methotrexate and their interactions with H/sub 2/ folate reductase was evaluated. Methotrexate polyglutamates were detected within 15 minutes in hepatocytes exposed to 1 microM methotrexate, and continued to accumulate for at least 60 minutes producing a large transmembrane gradient. These derivatives appeared to be preferentially retained within the cell. In studies with the Ehrlich ascites tumor accumulation of methotrexate polyglutamates was increased over 5-fold by the addition of 5 mM L-glutamine or L-glutamate and exhibited a positive correlation with the extracellular concentration of methotrexate. When Ehrlich ascites tumor cells were exposed to 10 microM methotrexate and 5 mM L-glutamine intracellular polyglutamates were detected within 10 minutes and their levels increased linearly over 4 hours. As these derivatives accumulated, there was a decline in intracellular methotrexate due at least in part to a replacement of methotrexate on H/sub 2/ folate reductase by polyglutamates and subsequent efflux of the previously bound methotrexate from the cell. When polyglutamate derivatives were in excess of the H/sub 2/ folate reductase binding capacity and extracellular methotrexate removed, methotrexate rapidly exited the cell whereas the majority of its metabolites were retained and eventually saturated the major portion of the enzyme. These studies indicate that (1) intracellular methotrexate is rapidly converted to polygammaglutamyl derivatives, (2) these metabolites effectively compete with methotrexate for binding sites on H/sub 2/ folate reductase, (3) these derivatives are retained within the cell more effectively than methotrexate, and (4) vincristine and probenecid may be potentially useful for selectively increasing methotrexate polyglutamates in tumor cells.

  4. Equine testicular interstitial cell tumors.

    PubMed

    Gelberg, H B; McEntee, K

    1987-05-01

    Interstitial cell tumors from nine stallions were described. In all but one horse the tumors were found in undescended testes. Five animals had bilateral tumors. Two animals showed increased aggression. Tumors contained two cell types. The first type were large distinctly bordered eosinophilic cells interpreted to be hyperplastic and hypertrophic interstitial cells. They blended with pleomorphic often spindloid neoplastic cells which had fibrillar, vacuolated cytoplasm and indistinct cell borders. This latter cell population was arranged in nodules or broad sheets as endocrine-like packets or interweaving fascicles. Biologic behavior of the neoplasms could not be ascertained from histologic examination. PMID:2885961

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

    PubMed Central

    2016-01-01

    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. PMID:27493669

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

    PubMed

    ElShamy, Wael M; Sinha, Abhilasha; Said, Neveen

    2016-01-01

    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. PMID:27493669

  7. Gender differences in reactive and proactive aggression.

    PubMed

    Connor, Daniel F; Steingard, Ronald J; Anderson, Jennifer J; Melloni, Richard H

    2003-01-01

    The purpose of our investigation was to study gender differences in proactive and reactive aggression in a sample of 323 clinically referred children and adolescents (68 females and 255 males). Proactive aggression and reactive aggression were assessed using the Proactive/Reactive Aggression Scale. Demographic, historical, family, diagnostic, and treatment variables were entered into stepwise regression analyses to determine correlates of proactive and reactive aggression in males and females. Results reveal high rates of aggression in both males and females in the sample. Self reported drug use, expressed hostility, and experiences of maladaptive parenting were correlated with proactive aggression for both genders. Hyperactive/impulsive behaviors were correlated with male reactive aggression. An early age of traumatic stress and a low verbal IQ were correlated with female proactive aggression. Gender differences in correlates of proactive and reactive aggression may provide possible targets for research, prevention, and treatment efforts focused on reducing maladaptive aggression in clinically referred youth. PMID:12723901

  8. Regulation of UHRF1 by dual-strand tumor-suppressor microRNA-145 (miR-145-5p and miR-145-3p): inhibition of bladder cancer cell aggressiveness

    PubMed Central

    Matsushita, Ryosuke; Yoshino, Hirofumi; Enokida, Hideki; Goto, Yusuke; Miyamoto, Kazutaka; Yonemori, Masaya; Inoguchi, Satoru; Nakagawa, Masayuki; Seki, Naohiko

    2016-01-01

    In microRNA (miRNA) biogenesis, the guide-strand of miRNA integrates into the RNA induced silencing complex (RISC), whereas the passenger-strand is inactivated through degradation. Analysis of our miRNA expression signature of bladder cancer (BC) by deep-sequencing revealed that microRNA (miR)-145-5p (guide-strand) and miR-145-3p (passenger-strand) were significantly downregulated in BC tissues. It is well known that miR-145-5p functions as a tumor suppressor in several types of cancer. However, the impact of miR-145-3p on cancer cells is still ambiguous. The aim of the present study was to investigate the functional significance of miR-145-3p and BC oncogenic pathways and targets regulated by miR-145-5p/miR-145-3p. Ectopic expression of either miR-145-5p or miR-145-3p in BC cells significantly suppressed cancer cell growth, migration and invasion and it also induced apoptosis. The gene encoding ubiquitin-like with PHD and ring finger domains 1 (UHRF1) was a direct target of these miRNAs. Silencing of UHRF1 induced apoptosis and inhibited cancer cell proliferation, migration, and invasion in BC cells. In addition, overexpressed UHRF1 was confirmed in BC clinical specimens, and the high UHRF1 expression group showed a significantly poorer cause specific survival rate in comparison with the low expression group. Taken together, our present data demonstrated that both strands of miR-145 (miR-145-5p: guide-strand and miR-145-3p: passenger-strand) play pivotal roles in BC cells by regulating UHRF1. The identification of the molecular target of a tumor suppressive miRNAs provides novel insights into the potential mechanisms of BC oncogenesis and suggests novel therapeutic strategies. PMID:27072587

  9. Hypoxia enhances aggressiveness of cholangiocarcinoma cells.

    PubMed

    Seubwai, Wunchana; Kraiklang, Ratthaphol; Wongkham, Chaisiri; Wongkham, Sopit

    2012-01-01

    Hypoxia, a common feature of solid tumors, plays a significant role in determining tumor phenotype and tumor progression. In this study, using an in-house PCR-array, we investigated phenotypic changes and differentially expressed hypoxia related genes in the KKU-M213 CCA cell line, cultured under hypoxic (1% O2) condition. Trefoil factor-1 (TFF1), a disintegrin, and metalloprotease 12 (ADAM12), integrin-alpha 5 (ITGA5) and baculoviral IAP repeat-containing 5 (BIRC5/survivin), proteins involved with cell proliferation, metastasis and apoptosis resistance, were up-regulated whereas uridine 5'-monophosphate synthase (UMPS) and S100 calcium binding protein P (S100P), involved with chemosensitivity and cell adhesion, were down-regulated. Growth arrest, apoptosis resistance to UV-irradiation and chemotherapeutic drugs (5- flourouracil, cisplatin, doxorubicin) as well as cell adhesion were thus significantly enhanced upon exposure to hypoxic condition. These findings emphasize the significance of a hypoxic state in the induction of an aggressive phenotype and suggest the potential of targeting hypoxia regulated genes to enhance the sensitivity of chemotherapeutic drug against CCA.

  10. Aggressive Extraocular Sebaceous Carcinoma Recurring after Mohs Micrographic Surgery

    PubMed Central

    Grigoryan, Konstantin V.; Leithauser, Laurel; Gloster, Hugh M.

    2015-01-01

    Sebaceous carcinomas (SC) are rare adnexal tumors with possible aggressive behavior usually arising in the head and neck region of adults in the seventh decade of life. Treatment has traditionally been with surgical excision with 5-6 mm wide margins but Mohs micrographic surgery (MMS) has also been reported as an effective treatment modality. We present a case of a Caucasian female renal transplant patient with a rapidly enlarging nodule on the left preauricular cheek that was excised with MMS with negative margins. The tumor recurred rapidly and metastasized ultimately leading to the death of the patient. There was some disagreement amongst pathologists as to the possible nature of the diagnosis with the original biopsy being labeled as a poorly differentiated carcinoma. We aim to highlight the potential aggressive nature of SC and review the features of the neoplasm including histological features that help in making the diagnosis. PMID:25685571

  11. Role of Radiotherapy in Aggressive Digital Papillary Adenocarcinoma.

    PubMed

    Feldmeyer, Laurence; Prieto, Victor G; Ivan, Doina; Nagarajan, Priyadharsini; Tetzlaff, Michael T; Curry, Jonathan L; Bell, Diana; Moon, Bryan S; Torres-Cabala, Carlos A; Aung, Phyu P

    2016-01-01

    Aggressive digital papillary adenocarcinoma (ADPA) is a rare and often misdiagnosed malignant tumor of the sweat glands, most commonly encountered on the extremities. Due to the relatively high metastatic potential of the tumor, aggressive surgical treatment, including amputation, is generally recommended. We present a case of a 36-year-old male with an over 10-year history of a skin lesion on the right hand in the web space between the index and the middle finger. Histologically, the lesion revealed a malignant epithelioid neoplasm with features consistent with ADPA. The lesion was treated with 5-weeks preoperative radiation (total 5000 cGy) followed by surgical resection. There was no evidence of residual disease confirmed by pathological study of re-excision specimen as well as imaging studies. This is, to the best of knowledge, the first report of complete regression of an ADPA after radiotherapy. PMID:27098633

  12. "Primary" aggressive chondroblastoma of the humerus: a case report

    PubMed Central

    Harish, K; Janaki, MG; Alva, N Kishore

    2004-01-01

    Background Chondroblastomas are rare epiphyseal bone tumors. Very few cases with extra-cortical aggressive soft tissue invasion or metastasis are reported. Case presentation We report a 28 year-old adult male who presented with a large swelling over the left shoulder region. Pre-operative imaging revealed a large tumor arising from upper end of humerus with extensive soft tissue involvement necessitating a fore-quarter amputation. Patient received adjuvant radiation. Conclusions This patient is one of the largest chondroblastomas to be reported. Although chondroblastomas are typically benign, rarely they can be locally aggressive or metastatic. Early diagnosis and institution of proper primary therapy would prevent mutilating surgeries and recurrences. PMID:15113430

  13. Quantifying Aggressive Behavior in Zebrafish.

    PubMed

    Teles, Magda C; Oliveira, Rui F

    2016-01-01

    Aggression is a complex behavior that influences social relationships and can be seen as adaptive or maladaptive depending on the context and intensity of expression. A model organism suitable for genetic dissection of the underlying neural mechanisms of aggressive behavior is still needed. Zebrafish has already proven to be a powerful vertebrate model organism for the study of normal and pathological brain function. Despite the fact that zebrafish is a gregarious species that forms shoals, when allowed to interact in pairs, both males and females express aggressive behavior and establish dominance hierarchies. Here, we describe two protocols that can be used to quantify aggressive behavior in zebrafish, using two different paradigms: (1) staged fights between real opponents and (2) mirror-elicited fights. We also discuss the methodology for the behavior analysis, the expected results for both paradigms, and the advantages and disadvantages of each paradigm in face of the specific goals of the study. PMID:27464816

  14. Genetics of adrenal tumors.

    PubMed

    Opocher, G; Schiavi, F; Cicala, M V; Patalano, A; Mariniello, B; Boaretto, F; Zovato, S; Pignataro, V; Macino, B; Negro, I; Mantero, F

    2009-06-01

    The impact of genetics and genomics on clinical medicine is becoming more and more important. Endocrinology pioneered the development of molecular medicine, but also the study of adrenal tumors had a great impact in this field. Particularly important was the detection of genetics of tumors derived from the adrenal medulla, as well as that of those derived from the sympathetic and parasympathetic paraganglia. The identification of mutations in one of the several pheochromocytoma/paraganglioma susceptibility genes may indicate a specific clinical management drive. Less well understood is the genetics of adrenal cortex tumors, in particular adrenocortical carcinoma, a rare and particularly aggressive disease. There are only a few examples of hereditary transmission of adrenocortical carcinoma, but the analysis of low penetrance genes by genome wide association study may enable us to discover new genetic mechanisms responsible for adrenocortical-derived tumors. PMID:19471236

  15. Music, Substance Use, and Aggression

    PubMed Central

    Chen, Meng-Jinn; Miller, Brenda A.; Grube, Joel W.; Waiters, Elizabeth D.

    2016-01-01

    Objective This study investigated whether young people’s substance use and aggressive behaviors are related to their listening to music containing messages of substance use and violence. Method Data were collected using self-administered questionnaires and from a sample of community college students aged 15-25 (N = 1056; 43% male). A structural equation modeling method was used to simultaneously assess the associations between listening to various genres of music, alcohol use, illicit drug use, and aggressive behaviors, taking into account respondents’ age, gender, race/ethnicity, and level of sensation seeking. Results Listening to rap music was significantly and positively associated with alcohol use, problematic alcohol use, illicit drug use, and aggressive behaviors when all other variables were controlled. Additionally, alcohol and illicit drug use were positively associated with listening to musical genres of techno and reggae. Control variables such as sensation seeking, age, gender and race/ethnicity were significantly related to substance use and aggressive behaviors. Conclusion The findings suggest that young people’s substance use and aggressive behaviors may be related to their frequent exposure to music containing references to substance use and violence. Conversely, music listening preference may reflect some personal predispositions or lifestyle preferences. Alternatively, substance use, aggression and music preference are independent constructs, but share common “third factors.” PMID:16608146

  16. Malignant transformation of aggressive osteoblastoma to ostesarcoma.

    PubMed

    Görgün, Ömer; Salduz, Ahmet; Kebudi, Rejin; Özger, Harzem; Bilgiç, Bilge

    2016-08-01

    Osteoblastoma is a rare, bone-forming tumor, characterized by osteoid and woven bone production. A 13-year-old boy patient presented to our clinic with complaint of pain in his left proximal tibia. We performed curettage and bone grafting for the lesion diagnosed as osteoblastoma. Two years later, the patient admitted to the hospital with a mass in the same region which was diagnosed by biopsy to be osteosarcoma. Patient was performed reconstruction operation with local resection and mega prosthesis. Fourteen months after termination of chemotherapy, lung metastasis developed and the patient died consequently. In this article, we reported a patient with aggressive osteoblastoma of the left proximal tibia which recurred as an osteosarcoma and discussed the difficulties in the histopathological diagnosis and management of these patients. As some other cases in the literature, our case indicates that osteoblastomas may undergo malignant transformation. PMID:27499324

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

    PubMed

    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.

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

    PubMed

    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. PMID:23440595

  19. Impaired Nitric Oxide Synthase Signaling Dissociates Social Investigation and Aggression

    PubMed Central

    Trainor, Brian C.; Workman, Joanna L.; Jessen, Ruth; Nelson, Randy J.

    2007-01-01

    A combination of social withdrawal and increased aggression is characteristic of several mental disorders. Most previous studies have investigated the neurochemical bases of social behavior and aggression independently, as opposed to how these behaviors are regulated in concert. Neuronal nitric oxide synthase (nNOS) produces gaseous nitric oxide, which functions as a neurotransmitter and is known to affect several types of behavior including mating and aggression. Compared with wild-type mice, we observed that nNOS knockout mice showed reduced behavioral responses to an intruder behind a wire barrier. Similar results were observed in mice treated with the selective nNOS inhibitor 3-bromo-7-nitroindazole (3BrN). In habituation–dishabituation tests, treatment with 3BrN did not block recognition of male urine but did attenuate investigation time compared with oil-treated animals. Finally, nNOS knockout mice and 3BrN treated mice were significantly more aggressive than wild-type and oil-treated males, respectively. In general, these behavioral effects are less pronounced in pair-housed males compared with singly-housed males. Thus, nNOS inhibition results in a phenotype that displays reduced social investigation and increased aggression. These data suggest that further study of nNOS signaling is warranted in mental disorders characterized by social withdrawal and increased aggression. PMID:17469926

  20. Family history characteristics, tumor microsatellite instability and germline MSH2 and MLH1 mutations in hereditary colorectal cancer.

    PubMed

    Bapat, B V; Madlensky, L; Temple, L K; Hiruki, T; Redston, M; Baron, D L; Xia, L; Marcus, V A; Soravia, C; Mitri, A; Shen, W; Gryfe, R; Berk, T; Chodirker, B N; Cohen, Z; Gallinger, S

    1999-02-01

    Recent characterization of the molecular genetic basis of hereditary nonpolyposis colorectal cancer provides an important opportunity for identification of individuals and their families with germline mutations in mismatch repair genes. Cancer family history criteria that accurately define hereditary colorectal cancer are necessary for cost-effective testing for germline mutations in mismatch repair genes. The present report describes the results of analysis of 33 colorectal cancer cases/families that satisfy our modified family history criteria (Mount Sinai criteria) for colorectal cancer. Fourteen of these families met the more stringent Amsterdam criteria. Germline MSH2 and MLH1 mutations were identified by the reverse transcription-polymerase chain reaction and the protein truncation test, and confirmed by sequencing. Microsatellite instability analysis was performed on available tumors from affected patients. MSH2 or MLH1 mutations were detected in 8 of 14 Amsterdam criteria families and in 5 of the remaining 19 cases/families that only satisfied the Mount Sinai criteria. Three of the latter families had features of the Muir-Torre syndrome. A high level of microsatellite instability (MSI-H) was detected in almost all (16/18) colorectal cancers from individuals with MSH2 and MLH1 mutations, and infrequently (1/21) in colorectal cancer specimens from cases without detectable mutations. Families with germline MSH2 and MLH1 mutations tended to have individuals affected at younger ages and with multiple tumors. The Amsterdam criteria are useful, but not sufficient, for detecting hereditary colorectal cancer families with germline MSH2 and MLH1 mutations, since a proportion of cases and families with mutations in mismatch repair genes will be missed. Further development of cancer family history criteria are needed, using unbiased prospectively collected cases, to define more accurately those who will benefit from MSH2 and MLH1 mutation analysis. PMID:10190329

  1. [A little known entity: aggressive fibromatosis].

    PubMed

    Marqúes Gubern, A; Pérez Payarols, J; Sánchez de Toledo, J; Martínez Ibáñez, V; Moraga, F; de Torres Ramírez, I M

    1991-01-01

    Aggressive fibromatosis is an unfrequent and little known entity, which in spite of being a histologically benign tumoration with scarce mitosis and without metastasis at distance, frequently presents with a high degree of local malignancy that can cause serious functional and aesthetical disturbance for the patient and even lead to death if infiltration of vital organs is presented, above all in cases of abdominal or maxillo-facial mass localization. The authors present their experience with 17 cases of aggressive fibromatosis observed in our centre: four of abdominal localization, six in extremities, five in the maxillo-facial mass, one in the torax and one in the lumbo-sacral region. Histological diagnosis, either by puncture or biopsy, is complemented by studies of extension of the tumour based on ecography and TAC. All cases were treated according to the classical criteria of ample resection of the lesion, always when practicable, except in one infant case and in the torax, in which only a biopsy was effected. Of the 15 cases resected, nine cases had local relapses, six of which remained free of disease with a second operation, another two required a third operation and the remaining case needed five interventions. In six children chemotherapy was applied with vincristina, cyclophosphamide and adriamicina. A follow up was carried out in 14 patients, one of which died and the remaining 13 are free of disease. In spite of the fact that progestagene receptors were not evidenced in two of our cases, one presented complete remission of the tumor after treatment with medroxyprogesterone. In this case the coincidence of Gardner's syndrome arises in the family history.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2043434

  2. Do Teachers Misbehave? Aggression in School Teams

    ERIC Educational Resources Information Center

    Ben Sasson, Dvora; Somech, Anit

    2015-01-01

    Purpose: Despite growing research on school aggression, significant gaps remain in the authors' knowledge of team aggression, since most studies have mainly explored aggression on the part of students. The purpose of this paper is to focus on understanding the phenomenon of workplace aggression in school teams. Specifically, the purpose of the…

  3. Adolescents' Social Reasoning about Relational Aggression

    ERIC Educational Resources Information Center

    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…

  4. Hollingsworth - Aggressive vs Indolent 2012 — EDRN Public Portal

    Cancer.gov

    Study Overview. We will examine DNA extracted from FFPE sections from approximately 200 different surgically resected primary pancreatic tumors from the UNMC Department of Pathology and Microbiology. DNA will be purified from those sections and subjected to deep sequencing for the entire TP53 locus. Expected Outcomes We expect to find a difference in the p53 mutation status between tumor samples from patients that ultimately experienced tumor recurrence (more aggressive) compared to those that did not. Parallel studies to develop ICP will enable us to rapidly develop a low cost platform to extend these studies to larger patient populations for future validation studies. Future Studies The experiments proposed in this application represent a state-of-the-art approach to identify molecular markers that will help clinicians to ascertain the tumor recurrence risk for their pancreatic cancer patients who have undergone a Whipple procedure. If our initial studies support the hypothesis that p53 mutations are associated with early metastasis of pancreatic cancer, these studies would be extended to other cohorts of patient samples that are available at other major centers that see pancreatic cancer patients. Development of ICE COLD-PCR platforms to screen for these mutations will facilitate a reliable, rapid and low cost method for predicting tumor aggressiveness in these patients, which will be deployed in future studies should the hypothesis be supported.

  5. Impulsive Aggression as a Comorbidity of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents

    PubMed Central

    Amann, Birgit H.

    2016-01-01

    Abstract Objective: This article examines the characteristics of impulsive aggression (IA) as a comorbidity in children and adolescents with attention-deficit/hyperactivity disorder (ADHD), focusing on its incidence, impact on ADHD outcomes, need for timely intervention, and limitations of current treatment practices. Methods: Relevant literature was retrieved with electronic searches in PubMed and PsycINFO using the search strategy of “ADHD OR attention deficit hyperactivity disorder” AND “impulsive aggression OR reactive aggression OR hostile aggression OR overt aggression” AND “pediatric OR childhood OR children OR pre-adolescent OR adolescent” with separate searches using review OR clinical trial as search limits. Key articles published before the 2007 Expert Consensus Report on IA were identified using citation analysis. Results: More than 50% of preadolescents with ADHD combined subtype reportedly display clinically significant aggression, with impulsive aggression being the predominant subtype. Impulsive aggression is strongly predictive of a highly unfavorable developmental trajectory characterized by the potential for persistent ADHD, increasing psychosocial burden, accumulating comorbidities, serious lifelong functional deficits across a broad range of domains, delinquency/criminality, and adult antisocial behavior. Impulsive aggression, which triggers peer rejection and a vicious cycle of escalating dysfunction, may be a key factor in unfavorable psychosocial outcomes attributed to ADHD. Because severe aggressive behavior does not remit in many children when treated with primary ADHD therapy (i.e., stimulants and behavioral therapy), a common practice is to add medication of a different class to specifically target aggressive behavior. Conclusions: Impulsive aggression in children and adolescents with ADHD is a serious clinical and public health problem. Although adjunctive therapy with an aggression-targeted agent is widely recommended when

  6. Individual and contextual antecedents of workplace aggression in aged care nurses and certified nursing assistants.

    PubMed

    Rodwell, John; Demir, Defne; Gulyas, Andre

    2015-08-01

    Employees in aged care are at high risk of workplace aggression. Research rarely examines the individual and contextual antecedents of aggression for specific types of workers within these settings, such as nurses and certified nursing assistants (CNAs). The study aimed to explore characteristics of the job demands-resources model (JD-R), negative affectivity (NA) and demographics related to workplace aggression for aged care workers. The survey study was based on 208 nurses and 83 CNAs working within aged care. Data from each group were analysed separately using ordinal regressions. Both aged care nurses and CNAs reported high rates of bullying, external emotional abuse, threat of assault and physical assault. Elements of the JD-R model and individual characteristics were related to aggression types for both groups. Characteristics of the JD-R model, NA and demographics are important in understanding the antecedents of aggression observed among aged care workers.

  7. Superior sulcus tumors (Pancoast tumors).

    PubMed

    Marulli, Giuseppe; Battistella, Lucia; Mammana, Marco; Calabrese, Francesca; Rea, Federico

    2016-06-01

    Superior Sulcus Tumors, frequently termed as Pancoast tumors, are a wide range of tumors invading the apical chest wall. Due to its localization in the apex of the lung, with the potential invasion of the lower part of the brachial plexus, first ribs, vertebrae, subclavian vessels or stellate ganglion, the superior sulcus tumors cause characteristic symptoms, like arm or shoulder pain or Horner's syndrome. The management of superior sulcus tumors has dramatically evolved over the past 50 years. Originally deemed universally fatal, in 1956, Shaw and Paulson introduced a new treatment paradigm with combined radiotherapy and surgery ensuring 5-year survival of approximately 30%. During the 1990s, following the need to improve systemic as well as local control, a trimodality approach including induction concurrent chemoradiotherapy followed by surgical resection was introduced, reaching 5-year survival rates up to 44% and becoming the standard of care. Many efforts have been persecuted, also, to obtain higher complete resection rates using appropriate surgical approaches and involving multidisciplinary team including spine surgeon or vascular surgeon. Other potential treatment options are under consideration like prophylactic cranial irradiation or the addition of other chemotherapy agents or biologic agents to the trimodality approach.

  8. Superior sulcus tumors (Pancoast tumors).

    PubMed

    Marulli, Giuseppe; Battistella, Lucia; Mammana, Marco; Calabrese, Francesca; Rea, Federico

    2016-06-01

    Superior Sulcus Tumors, frequently termed as Pancoast tumors, are a wide range of tumors invading the apical chest wall. Due to its localization in the apex of the lung, with the potential invasion of the lower part of the brachial plexus, first ribs, vertebrae, subclavian vessels or stellate ganglion, the superior sulcus tumors cause characteristic symptoms, like arm or shoulder pain or Horner's syndrome. The management of superior sulcus tumors has dramatically evolved over the past 50 years. Originally deemed universally fatal, in 1956, Shaw and Paulson introduced a new treatment paradigm with combined radiotherapy and surgery ensuring 5-year survival of approximately 30%. During the 1990s, following the need to improve systemic as well as local control, a trimodality approach including induction concurrent chemoradiotherapy followed by surgical resection was introduced, reaching 5-year survival rates up to 44% and becoming the standard of care. Many efforts have been persecuted, also, to obtain higher complete resection rates using appropriate surgical approaches and involving multidisciplinary team including spine surgeon or vascular surgeon. Other potential treatment options are under consideration like prophylactic cranial irradiation or the addition of other chemotherapy agents or biologic agents to the trimodality approach. PMID:27429965

  9. Superior sulcus tumors (Pancoast tumors)

    PubMed Central

    Battistella, Lucia; Mammana, Marco; Calabrese, Francesca; Rea, Federico

    2016-01-01

    Superior Sulcus Tumors, frequently termed as Pancoast tumors, are a wide range of tumors invading the apical chest wall. Due to its localization in the apex of the lung, with the potential invasion of the lower part of the brachial plexus, first ribs, vertebrae, subclavian vessels or stellate ganglion, the superior sulcus tumors cause characteristic symptoms, like arm or shoulder pain or Horner’s syndrome. The management of superior sulcus tumors has dramatically evolved over the past 50 years. Originally deemed universally fatal, in 1956, Shaw and Paulson introduced a new treatment paradigm with combined radiotherapy and surgery ensuring 5-year survival of approximately 30%. During the 1990s, following the need to improve systemic as well as local control, a trimodality approach including induction concurrent chemoradiotherapy followed by surgical resection was introduced, reaching 5-year survival rates up to 44% and becoming the standard of care. Many efforts have been persecuted, also, to obtain higher complete resection rates using appropriate surgical approaches and involving multidisciplinary team including spine surgeon or vascular surgeon. Other potential treatment options are under consideration like prophylactic cranial irradiation or the addition of other chemotherapy agents or biologic agents to the trimodality approach. PMID:27429965

  10. Kindergarten Children's Genetic Vulnerabilities Interact with Friends' Aggression to Promote Children's Own Aggression

    ERIC Educational Resources Information Center

    van Lier, Pol; Boivin, Michel; Dionne, Ginette; Vitaro, Frank; Brendgen, Mara; Koot, Hans; Tremblay, Richard E.; Perusse, Daniel

    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 teacher and peer reports of aggression of the two best…

  11. Aggression as Positive Reinforcement in Mice under Various Ratio- and Time-Based Reinforcement Schedules

    ERIC Educational Resources Information Center

    May, Michael E.; Kennedy, Craig H.

    2009-01-01

    There is evidence suggesting aggression may be a positive reinforcer in many species. However, only a few studies have examined the characteristics of aggression as a positive reinforcer in mice. Four types of reinforcement schedules were examined in the current experiment using male Swiss CFW albino mice in a resident-intruder model of aggression…

  12. Social-Cognitive and Behavioral Attributes of Aggressive Victims of Bullying

    ERIC Educational Resources Information Center

    Toblin, R.L.; Schwartz, D.; Hopmeyer Gorman, A.; Abou-ezzeddine, T.

    2005-01-01

    This study examined the social-cognitive and behavioral attributes of children who are concurrently aggressive and victimized by their peers. The characteristics of these ''aggressive victims'' were examined in comparison to bullies, passive victims, and normative comparison children. The sample included 240 urban Los Angeles elementary school…

  13. Teacher-Child Relationship Quality and Children's Peer Victimization and Aggressive Behavior in Late Childhood

    ERIC Educational Resources Information Center

    Troop-Gordon, Wendy; Kopp, Jessica

    2011-01-01

    This investigation examines the extent to which characteristics of the teacher-child relationship (closeness, dependency, and conflict) are predictive of changes in children's peer victimization and aggressive behavior over the course of a school year. Relational and physical forms of victimization and aggression were studied, and changes in peer…

  14. How Real Is the Portrayal of Aggression in Television Entertainment Programming?

    ERIC Educational Resources Information Center

    Potter, W. James; And Others

    1995-01-01

    Assesses aggressive behavior on television in terms of its realism. Replicated and contextualized reality were assessed for 100.5 hours of programming. Replicated reality compared television portrayals to real world characteristics, and was similar in seriousness to aggression and gender patterns of perpetrators and victims. Contextual reality…

  15. Youth Aggression and Violence: Risk, Resilience, and Prevention. ERIC Digest #E602.

    ERIC Educational Resources Information Center

    Christle, Christine A.; Jolivette, Kristine; Nelson, C. Michael

    This brief paper summarizes the current literature concerning youth aggression and violence especially risk, resilience, and prevention. It summarizes risk factors for aggression and violence including child characteristics (e.g., hyperactivity, risk-taking, emotional disturbance), home conditions (e.g., harsh and ineffective parental discipline,…

  16. Neuropsychological Factors in the Evaluation and Treatment of Childhood and Adolescent Aggression.

    ERIC Educational Resources Information Center

    French, Laurence

    This paper addresses the neuropsychological evaluation of impulsive aggression in emotionally disturbed students. Specific complications of organic aggressive syndrome include its unpredictable nature and basis in organic etiology. Characteristically, there is a sudden onset of unprovoked rage and violence accompanied by a drastic change in…

  17. Linking Psychopathy and School Aggression in a Nonclinical Sample of Adolescents

    ERIC Educational Resources Information Center

    Gumpel, Thomas P.

    2014-01-01

    Antisocial behavior and school aggression in youth has been linked with affective, interpersonal, self-attributional, and behavioral characteristics; these traits have often been associated with psychopathic behaviors among adults. Psychopathic traits were examined in nonclinically-referred youth exhibiting antisocial and aggressive behavior.…

  18. Cognitive and Temperament Clusters in 3- to 5-Year-Old Children with Aggressive Behavior

    ERIC Educational Resources Information Center

    Sakimura, Jean N.; Dang, Michelle T.; Ballard, Kelley B.; Hansen, Robin L.

    2008-01-01

    Background: This study assessed the co-occurrence of cognitive problems and difficult temperament characteristics in children aged 3 to 5 years exhibiting aggressive behavior. Methods: Thirty-one children with high ratings on the Aggressive Behavior subscale of the Achenbach Child Behavior Checklist or Teacher Report Form were recruited from a…

  19. Mental Health Correlates of Aggression in Nursing Home Residents with Dementia

    ERIC Educational Resources Information Center

    Talerico, Karen Amann; Evans, Lois K.; Strumpf, Neville E.

    2002-01-01

    Purpose: Aggression continues to challenge caregivers of persons with dementia, and identification of foci for effective interventions is needed. The purpose of this study was to examine the influence of (a) the resident characteristics of depression, communication, and cognition and (b) behavior management strategies on aggression in a group of…

  20. An Implicit Theories of Personality Intervention Reduces Adolescent Aggression in Response to Victimization and Exclusion

    ERIC Educational Resources Information Center

    Yeager, David Scott; Trzesniewski, Kali H.; Dweck, Carol S.

    2013-01-01

    Adolescents are often resistant to interventions that reduce aggression in children. At the same time, they are developing stronger beliefs in the fixed nature of personal characteristics, particularly aggression. The present intervention addressed these beliefs. A randomized field experiment with a diverse sample of Grades 9 and 10 students (ages…

  1. A Qualitative Evaluation of Social-Cognitive Changes in Children with Reactively Aggressive Behaviors

    ERIC Educational Resources Information Center

    Fung, Annis L. C.

    2007-01-01

    The parent-child parallel group Anger Coping Training (ACT) program aimed to help reactively aggressive children in restructuring cognitive characteristics, so as to reduce childhood aggression. This research program involved experimental and control groups with pre- and postcomparison. Qualitative data were collected through 367 individual…

  2. Children's and Their Friends' Moral Reasoning: Relations with Aggressive Behavior

    ERIC Educational Resources Information Center

    Gasser, Luciano; Malti, Tina

    2012-01-01

    Friends' moral characteristics such as their moral reasoning represent an important social contextual factor for children's behavioral socialization. Guided by this assumption, we compared the effects of children's and friends' moral reasoning on their aggressive behavior in a low-risk sample of elementary school children. Peer nominations and…

  3. PI3K/AKT/mTOR and sonic hedgehog pathways cooperate together to inhibit human pancreatic cancer stem cell characteristics and tumor growth

    PubMed Central

    Sharma, Narinder; Nanta, Rajesh; Sharma, Jay; Gunewardena, Sumedha; Singh, Karan P.; Shankar, Sharmila; Srivastava, Rakesh K.

    2015-01-01

    Cancer stem cells (CSCs) play major roles in cancer initiation, progression, and metastasis. It is evident from growing reports that PI3K/Akt/mTOR and Sonic Hedgehog (Shh) signaling pathways are aberrantly reactivated in pancreatic CSCs. Here, we examined the efficacy of combining NVP-LDE-225 (PI3K/mTOR inhibitor) and NVP-BEZ-235 (Smoothened inhibitor) on pancreatic CSCs characteristics, microRNA regulatory network, and tumor growth. NVP-LDE-225 co-operated with NVP-BEZ-235 in inhibiting pancreatic CSC's characteristics and tumor growth in mice by acting at the level of Gli. Combination of NVP-LDE-225 and NVP-BEZ-235 inhibited self-renewal capacity of CSCs by suppressing the expression of pluripotency maintaining factors Nanog, Oct-4, Sox-2 and c-Myc, and transcription of Gli. NVP-LDE-225 co-operated with NVP-BEZ-235 to inhibit Lin28/Let7a/Kras axis in pancreatic CSCs. Furthermore, a superior interaction of these drugs was observed on spheroid formation by pancreatic CSCs isolated from Pankras/p53 mice. The combination of these drugs also showed superior effects on the expression of proteins involved in cell proliferation, survival and apoptosis. In addition, NVP-LDE-225 co-operated with NVP-BEZ-235 in inhibiting EMT through modulation of cadherin, vimentin and transcription factors Snail, Slug and Zeb1. In conclusion, these data suggest that the combined inhibition of PI3K/Akt/mTOR and Shh pathways may be beneficial for the treatment of pancreatic cancer. PMID:26451606

  4. PI3K/AKT/mTOR and sonic hedgehog pathways cooperate together to inhibit human pancreatic cancer stem cell characteristics and tumor growth.

    PubMed

    Sharma, Narinder; Nanta, Rajesh; Sharma, Jay; Gunewardena, Sumedha; Singh, Karan P; Shankar, Sharmila; Srivastava, Rakesh K

    2015-10-13

    Cancer stem cells (CSCs) play major roles in cancer initiation, progression, and metastasis. It is evident from growing reports that PI3K/Akt/mTOR and Sonic Hedgehog (Shh) signaling pathways are aberrantly reactivated in pancreatic CSCs. Here, we examined the efficacy of combining NVP-LDE-225 (PI3K/mTOR inhibitor) and NVP-BEZ-235 (Smoothened inhibitor) on pancreatic CSCs characteristics, microRNA regulatory network, and tumor growth. NVP-LDE-225 co-operated with NVP-BEZ-235 in inhibiting pancreatic CSC's characteristics and tumor growth in mice by acting at the level of Gli. Combination of NVP-LDE-225 and NVP-BEZ-235 inhibited self-renewal capacity of CSCs by suppressing the expression of pluripotency maintaining factors Nanog, Oct-4, Sox-2 and c-Myc, and transcription of Gli. NVP-LDE-225 co-operated with NVP-BEZ-235 to inhibit Lin28/Let7a/Kras axis in pancreatic CSCs. Furthermore, a superior interaction of these drugs was observed on spheroid formation by pancreatic CSCs isolated from Pankras/p53 mice. The combination of these drugs also showed superior effects on the expression of proteins involved in cell proliferation, survival and apoptosis. In addition, NVP-LDE-225 co-operated with NVP-BEZ-235 in inhibiting EMT through modulation of cadherin, vimentin and transcription factors Snail, Slug and Zeb1. In conclusion, these data suggest that the combined inhibition of PI3K/Akt/mTOR and Shh pathways may be beneficial for the treatment of pancreatic cancer. PMID:26451606

  5. Aggression differentially modulates brain responses to fearful and angry faces: an exploratory study.

    PubMed

    Lu, Hui; Wang, Yu; Xu, Shuang; Wang, Yifeng; Zhang, Ruiping; Li, Tsingan

    2015-08-19

    Aggression is reported to modulate neural responses to the threatening information. However, whether aggression can modulate neural response to different kinds of threatening facial expressions (angry and fearful expressions) remains unknown. Thus, event-related potentials were measured in individuals (13 high aggressive, 12 low aggressive) exposed to neutral, angry, and fearful facial expressions while performing a frame-distinguishing task, irrespective of the emotional valence of the expressions. Highly aggressive participants showed no distinct neural responses between the three facial expressions. In addition, compared with individuals with low aggression, highly aggressive individuals showed a decreased frontocentral response to fearful faces within 250-300 ms and to angry faces within 400-500 ms of exposure. These results indicate that fearful faces represent a more threatening signal requiring a quick cognitive response during the early stage of facial processing, whereas angry faces elicit a stronger response during the later processing stage because of its eminent emotional significance. The present results represent the first known evidence that aggression is associated with different neural responses to fearful and angry faces. By exploring the distinct temporal responses to fearful and angry faces modulated by aggression, this study more precisely characterizes the cognitive characteristics of aggressive individuals. PMID:26164452

  6. A longitudinal study of the association between violent video game play and aggression among adolescents.

    PubMed

    Willoughby, Teena; Adachi, Paul J C; Good, Marie

    2012-07-01

    In the past 2 decades, correlational and experimental studies have found a positive association between violent video game play and aggression. There is less evidence, however, to support a long-term relation between these behaviors. This study examined sustained violent video game play and adolescent aggressive behavior across the high school years and directly assessed the socialization (violent video game play predicts aggression over time) versus selection hypotheses (aggression predicts violent video game play over time). Adolescents (N = 1,492, 50.8% female) were surveyed annually from Grade 9 to Grade 12 about their video game play and aggressive behaviors. Nonviolent video game play, frequency of overall video game play, and a comprehensive set of potential 3rd variables were included as covariates in each analysis. Sustained violent video game play was significantly related to steeper increases in adolescents' trajectory of aggressive behavior over time. Moreover, greater violent video game play predicted higher levels of aggression over time, after controlling for previous levels of aggression, supporting the socialization hypothesis. In contrast, no support was found for the selection hypothesis. Nonviolent video game play also did not predict higher levels of aggressive behavior over time. Our findings, and the fact that many adolescents play video games for several hours every day, underscore the need for a greater understanding of the long-term relation between violent video games and aggression, as well as the specific game characteristics (e.g., violent content, competition, pace of action) that may be responsible for this association.

  7. Sex differences in structural brain asymmetry predict overt aggression in early adolescents.

    PubMed

    Visser, Troy A W; Ohan, Jeneva L; Whittle, Sarah; Yücel, Murat; Simmons, Julian G; Allen, Nicholas B

    2014-04-01

    The devastating social, emotional and economic consequences of human aggression are laid bare nightly on newscasts around the world. Aggression is principally mediated by neural circuitry comprising multiple areas of the prefrontal cortex and limbic system, including the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), amygdala and hippocampus. A striking characteristic of these regions is their structural asymmetry about the midline (i.e. left vs right hemisphere). Variations in these asymmetries have been linked to clinical disorders characterized by aggression and the rate of aggressive behavior in psychiatric patients. Here, we show for the first time that structural asymmetries in prefrontal cortical areas are also linked to aggression in a normal population of early adolescents. Our findings indicate a relationship between parent reports of aggressive behavior in adolescents and structural asymmetries in the limbic and paralimbic ACC and OFC, and moreover, that this relationship varies by sex. Furthermore, while there was no relationship between aggression and structural asymmetries in the amygdala or hippocampus, hippocampal volumes did predict aggression in females. Taken together, the results suggest that structural asymmetries in the prefrontal cortex may influence human aggression, and that the anatomical basis of aggression varies substantially by sex.

  8. Aggression differentially modulates brain responses to fearful and angry faces: an exploratory study.

    PubMed

    Lu, Hui; Wang, Yu; Xu, Shuang; Wang, Yifeng; Zhang, Ruiping; Li, Tsingan

    2015-08-19

    Aggression is reported to modulate neural responses to the threatening information. However, whether aggression can modulate neural response to different kinds of threatening facial expressions (angry and fearful expressions) remains unknown. Thus, event-related potentials were measured in individuals (13 high aggressive, 12 low aggressive) exposed to neutral, angry, and fearful facial expressions while performing a frame-distinguishing task, irrespective of the emotional valence of the expressions. Highly aggressive participants showed no distinct neural responses between the three facial expressions. In addition, compared with individuals with low aggression, highly aggressive individuals showed a decreased frontocentral response to fearful faces within 250-300 ms and to angry faces within 400-500 ms of exposure. These results indicate that fearful faces represent a more threatening signal requiring a quick cognitive response during the early stage of facial processing, whereas angry faces elicit a stronger response during the later processing stage because of its eminent emotional significance. The present results represent the first known evidence that aggression is associated with different neural responses to fearful and angry faces. By exploring the distinct temporal responses to fearful and angry faces modulated by aggression, this study more precisely characterizes the cognitive characteristics of aggressive individuals.

  9. Tumor characteristics of ductal carcinoma in situ of breast visualized on [F-18] fluorodeoxyglucose-positron emission tomography/computed tomography: Results from a retrospective study

    PubMed Central

    Fujioka, Tomoyuki; Kubota, Kazunori; Toriihara, Akira; Machida, Youichi; Okazawa, Kaori; Nakagawa, Tsuyoshi; Saida, Yukihisa; Tateishi, Ukihide

    2016-01-01

    AIM To clarify clinicopathological features of ductal carcinoma in situ (DCIS) visualized on [F-18] fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT). METHODS This study retrospectively reviewed 52 consecutive tumors in 50 patients with pathologically proven pure DCIS who underwent [F-18] FDG-PET/CT before surgery. [F-18] FDG-PET/CT was performed after biopsy in all patients. The mean interval from biopsy to [F-18] FDG-PET/CT was 29.2 d. [F-18] FDG uptake by visual analysis and maximum standardized uptake value (SUVmax) was compared with clinicopathological characteristics. RESULTS [F-18] FDG uptake was visualized in 28 lesions (53.8%) and the mean and standard deviation of SUVmax was 1.63 and 0.90. On univariate analysis, visual analysis and the SUVmax were associated with symptomatic presentation (P = 0.012 and 0.002, respectively), palpability (P = 0.030 and 0.024, respectively), use of core-needle biopsy (CNB) (P = 0.023 and 0.012, respectively), ultrasound-guided biopsy (P = 0.040 and 0.006, respectively), enhancing lesion ≥ 20 mm on magnetic resonance imaging (MRI) (P = 0.001 and 0.010, respectively), tumor size ≥ 20 mm on histopathology (P = 0.002 and 0.008, respectively). However, [F-18] FDG uptake parameters were not significantly associated with age, presence of calcification on mammography, mass formation on MRI, presence of comedo necrosis, hormone status (estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2), and nuclear grade. The factors significantly associated with visual analysis and SUVmax were symptomatic presentation (P = 0.019 and 0.001, respectively), use of CNB (P = 0.001 and 0.031, respectively), and enhancing lesion ≥ 20 mm on MRI (P = 0.001 and 0.049, respectively) on multivariate analysis. CONCLUSION Although DCIS of breast is generally non-avid tumor, symptomatic and large tumors (≥ 20 mm) tend to be visualized on [F-18] FDG-PET/CT. PMID:27648168

  10. Vasculogenic mimicry and tumor metastasis.

    PubMed

    Zhang, Jingxin; Qiao, Lili; Liang, Ning; Xie, Jian; Luo, Hui; Deng, Guodong; Zhang, Jiandong

    2016-01-01

    Vasculogenic mimicry (VM), a microvascular channel made up of nonendothelial cells, has been accepted as a new model of neovascularization in aggressive tumors, owning to the specific capacity of malignant cells to form vessel-like networks which provide sufficient blood supply for tumor growth. Multiple molecular mechanisms, especially vascular endothelial (VE)-cadherin, erythropoietin-producing hepatocellular receptor A2 (EphA2), phosphatidyl inositol 3-kinase (PI3K), matrix metalloproteinases (MMPs), vascular endothelial growth factor receptor (VEGFR1), and hypoxia inducible factor (HIF)-1a, have been reported to participate in VM formation which is associated with tumor migration and invasion. In addition, hypoxia, cancer stem cells (CSCs) and epithelial-mesenehymal transition (EMT) are regarded as significant factors in VM formation and tumor metastasis. Due to the important effects of VM on tumor progression, a review was carried out in the present study, to synthetically analyze the relationship between VM and tumor metastasis. PMID:27569069

  11. Mitochondrial oncobioenergetic index: A potential biomarker to predict progression from indolent to aggressive prostate cancer

    PubMed Central

    Vayalil, Praveen K.; Landar, Aimee

    2015-01-01

    Mitochondrial function is influenced by alterations in oncogenes and tumor suppressor genes and changes in the microenvironment occurring during tumorigenesis. Therefore, we hypothesized that mitochondrial function will be stably and dynamically altered at each stage of the prostate tumor development. We tested this hypothesis in RWPE-1 cells and its tumorigenic clones with progressive malignant characteristics (RWPE-1 < WPE-NA22 < WPE-NB14 < WPE-NB11 < WPE-NB26) using high-throughput respirometry. Our studies demonstrate that mitochondrial content do not change with increasing malignancy. In premalignant cells (WPE-NA22 and WPE-NB14), OXPHOS is elevated in presence of glucose or glutamine alone or in combination compared to RWPE-1 cells and decreases with increasing malignancy. Glutamine maintained higher OXPHOS than glucose and suggests that it may be an important substrate for the growth and proliferation of prostate epithelial cells. Glycolysis significantly increases with malignancy and follow a classical Warburg phenomenon. Fatty acid oxidation (FAO) is significantly lower in tumorigenic clones and invasive WPE-NB26 does not utilize FAO at all. In this paper, we introduce for the first time the mitochondrial oncobioenergetic index (MOBI), a mathematical representation of oncobioenergetic profile of a cancer cell, which increases significantly upon transformation into localized premalignant form and rapidly falls below the normal as they become aggressive in prostate tumorigenesis. We have validated this in five prostate cancer cell lines and MOBI appears to be not related to androgen dependence or mitochondrial content, but rather dependent on the stage of the cancer. Altogether, we propose that MOBI could be a potential biomarker to distinguish aggressive cancer from that of indolent disease. PMID:26515588

  12. Human Breast Cancer Invasion and Aggression Correlates with ECM Stiffening and Immune Cell Infiltration

    PubMed Central

    Acerbi, I; Cassereau, L; Dean, I; Shi, Q; Au, A; Park, C; Chen, YY; Liphardt, J; Hwang, ES; Weaver, VM

    2015-01-01

    Tumors are stiff and data suggest that the extracellular matrix stiffening that correlates with experimental mammary malignancy drives tumor invasion and metastasis. Nevertheless, the relationship between tissue and extracellular matrix stiffness and human breast cancer progression and aggression remains unclear. We undertook a biophysical and biochemical assessment of stromal-epithelial interactions in noninvasive, invasive and normal adjacent human breast tissue and in breast cancers of increasingly aggressive subtype. Our analysis revealed that human breast cancer transformation is accompanied by an incremental increase in collagen deposition and a progressive linearization and thickening of interstitial collagen. The linearization of collagen was visualized as an overall increase in tissue birefringence and was most striking at the invasive front of the tumor where the stiffness of the stroma and cellular mechanosignaling were the highest. Amongst breast cancer subtypes we found that the stroma at the invasive region of the more aggressive Basal-like and Her2 tumor subtypes was the most heterogeneous and the stiffest when compared to the less aggressive Luminal A and B subtypes. Intriguingly, we quantified the greatest number of infiltrating macrophages and the highest level of TGF beta signaling within the cells at the invasive front. We also established that stroma stiffness and the level of cellular TGF beta signaling positively correlated with each other and with the number of infiltrating tumor-activated, macrophages, which was highest in the more aggressive tumor subtypes. These findings indicate that human breast cancer progression and aggression, collagen linearization and stromal stiffening are linked and implicate tissue inflammation and TGF beta. PMID:25959051

  13. Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration.

    PubMed

    Acerbi, I; Cassereau, L; Dean, I; Shi, Q; Au, A; Park, C; Chen, Y Y; Liphardt, J; Hwang, E S; Weaver, V M

    2015-10-01

    Tumors are stiff and data suggest that the extracellular matrix stiffening that correlates with experimental mammary malignancy drives tumor invasion and metastasis. Nevertheless, the relationship between tissue and extracellular matrix stiffness and human breast cancer progression and aggression remains unclear. We undertook a biophysical and biochemical assessment of stromal-epithelial interactions in noninvasive, invasive and normal adjacent human breast tissue and in breast cancers of increasingly aggressive subtype. Our analysis revealed that human breast cancer transformation is accompanied by an incremental increase in collagen deposition and a progressive linearization and thickening of interstitial collagen. The linearization of collagen was visualized as an overall increase in tissue birefringence and was most striking at the invasive front of the tumor where the stiffness of the stroma and cellular mechanosignaling were the highest. Amongst breast cancer subtypes we found that the stroma at the invasive region of the more aggressive Basal-like and Her2 tumor subtypes was the most heterogeneous and the stiffest when compared to the less aggressive luminal A and B subtypes. Intriguingly, we quantified the greatest number of infiltrating macrophages and the highest level of TGF beta signaling within the cells at the invasive front. We also established that stroma stiffness and the level of cellular TGF beta signaling positively correlated with each other and with the number of infiltrating tumor-activated macrophages, which was highest in the more aggressive tumor subtypes. These findings indicate that human breast cancer progression and aggression, collagen linearization and stromal stiffening are linked and implicate tissue inflammation and TGF beta. PMID:25959051

  14. Pathophysiological Basis for the Formation of the Tumor Microenvironment

    PubMed Central

    Horsman, Michael R.; Vaupel, Peter

    2016-01-01

    Poor microenvironmental conditions are a characteristic feature of solid tumors. Such conditions occur because the tumor vascular supply, which develops from the normal host vasculature by the process of angiogenesis, is generally inadequate in meeting the oxygen and nutrient demands of the growing tumor mass. Regions of low oxygenation (hypoxia) is believed to be the most critical deficiency, since it has been well documented to play a significant role in influencing the response to conventional radiation and chemotherapy treatments, as well as influencing malignant progression in terms of aggressive growth and recurrence of the primary tumor and its metastatic spread. As a result, significant emphasis has been placed on finding clinically applicable approaches to identify those tumors that contain hypoxia and realistic methods to target this hypoxia. However, most studies consider hypoxia as a single entity, yet we now know that it is multifactorial. Furthermore, hypoxia is often associated with other microenvironmental parameters, such as elevated interstitial fluid pressure, glycolysis, low pH, and reduced bioenergetic status, and these can also influence the effects of hypoxia. Here, we review the various aspects of hypoxia, but also discuss the role of the other microenvironmental parameters associated with hypoxia. PMID:27148472

  15. Multimodality Treatment in Ewing's Sarcoma Family Tumors of the Maxilla and Maxillary Sinus: Review of the Literature

    PubMed Central

    Mamot, Christoph; Krasniqi, Fatime; Metternich, Frank

    2016-01-01

    The Ewing sarcoma family of tumors (ESFT) encompasses a group of highly aggressive, morphologically similar, malignant neoplasms sharing a common spontaneous genetic translocation that affect mostly children and young adults. These predominantly characteristic, small round-cell tumors include Ewing's sarcoma of the bone and soft tissue, as well as primitive neuroectodermal tumors (PNETs) involving the bone, soft tissue, and thoracopulmonary region (Askin's tumor). Extraosseous ESFTs are extremely rare, especially in the head and neck region, where literature to date consists of sporadic case reports and very small series. We hereby present a review of the literature published on ESFTs reported in the maxilla and maxillary sinus region from 1968 to 2016. PMID:27413360

  16. A two-factor model of aggression.

    PubMed

    Kingsbury, S J; Lambert, M T; Hendrickse, W

    1997-01-01

    This article synthesizes theoretical material from psychology research into a practical model for conceptualizing violence in psychiatric settings. Relevant research and theory are reviewed, focusing on two important behavioral models of aggressive behavior, hostile aggression and instrumental aggression. The concepts of reinforcement, anticipated rewards, specific and nonspecific stimulus-driven aggression, intermediary emotional states in aroused persons, and the aggression stimulus threshold are developed into a bimodal model applicable to the clinical management of violence. The model provides a broad framework for categorizing, understanding, and addressing aggressive behavior in clinical settings.

  17. Tumor heterogeneity and circulating tumor cells.

    PubMed

    Zhang, Chufeng; Guan, Yan; Sun, Yulan; Ai, Dan; Guo, Qisen

    2016-05-01

    In patients with cancer, individualized treatment strategies are generally guided by an analysis of molecular biomarkers. However, genetic instability allows tumor cells to lose monoclonality and acquire genetic heterogeneity, an important characteristic of tumors, during disease progression. Researchers have found that there is tumor heterogeneity between the primary tumor and metastatic lesions, between different metastatic lesions, and even within a single tumor (either primary or metastatic). Tumor heterogeneity is associated with heterogeneous protein functions, which lowers diagnostic precision and consequently becomes an obstacle to determining the appropriate therapeutic strategies for individual cancer patients. With the development of novel testing technologies, an increasing number of studies have attempted to explore tumor heterogeneity by examining circulating tumor cells (CTCs), with the expectation that CTCs may comprehensively represent the full spectrum of mutations and/or protein expression alterations present in the cancer. In addition, this strategy represents a minimally invasive approach compared to traditional tissue biopsies that can be used to dynamically monitor tumor evolution. The present article reviews the potential efficacy of using CTCs to identify both spatial and temporal tumor heterogeneity. This review also highlights current issues in this field and provides an outlook toward future applications of CTCs.

  18. Sinus Tumors

    MedlinePlus

    ... Tumors Nasal Deformities Choanal Atresia Epiphora (Excessive Tearing) Disclosure Statement Printer Friendly Sinus Tumors Abtin Tabaee, MD Introduction Tumors of the nose and paranasal sinuses are rare, accounting for fewer than 1% of all tumors. These ...

  19. Desmoid Tumors in the Pediatric Population

    PubMed Central

    Honeyman, Joshua N.; La Quaglia, Michael P.

    2012-01-01

    Desmoid tumors are benign soft tissue tumors associated with locally aggressive growth and high rates of morbidity, but they do not metastasize via lymphatic or hematogenous routes. While most of the data on desmoid tumors originates in the adult literature, many of the findings have been applied to the management of pediatric patients. This article discusses the epidemiology, etiology, clinical presentation, pathology, and treatment of this rare tumor in the pediatric population and includes a literature review of the most recent large series of pediatric patients with desmoid tumors. PMID:24213241

  20. The Passive Aggressive Conflict Cycle

    ERIC Educational Resources Information Center

    Whitson, Signe

    2013-01-01

    Understanding the Passive Aggressive Conflict Cycle (PACC) helps observers to be able to look beyond behavior and better understand what is occurring beneath the surface. This article presents a real-life example of a seemingly minor conflict between a teacher and child that elicited an apparent major overreaction by the adult. Also provided is a…

  1. Epilepsy, aggression, and criminal responsibility.

    PubMed

    Borum, R; Appelbaum, K L

    1996-07-01

    Although epilepsy-related violence can occur, accounts of criminal behavior caused by epilepsy remain rare and unconvincing. The authors describe a case of apparent postictal aggression, resulting in felony assault charges, by a patient who had nocturnal complex partial seizures, followed by what appeared to be sleepwalking and periods of postictal wandering and confusion.

  2. Television Portrayal and Aggressive Behavior.

    ERIC Educational Resources Information Center

    Comstock, George

    This is a review of research relating to the attributes of portrayals which play a role in affecting aggressive behavior. The effects of portrayal can occur at any of three successive stages: acquisition, disinhibition/stimulation/arousal, performance. The older the individual, the more likely the influence is to be in all three stages of…

  3. Enrichment and aggression in primates.

    PubMed

    Honess, P E; Marin, C M

    2006-01-01

    There is considerable evidence that primates housed under impoverished conditions develop behavioural abnormalities, including, in the most extreme example, self-harming behaviour. This has implications for all contexts in which primates are maintained in captivity from laboratories to zoos since by compromising the animals' psychological well-being and allowing them to develop behavioural abnormalities their value as appropriate educational and research models is diminished. This review examines the extensive body of literature documenting attempts to improve living conditions with a view to correcting behavioural abnormalities and housing primates in such a way that they are encouraged to exhibit a more natural range and proportion of behaviours, including less self-directed and social aggression. The results of housing, feeding, physical, sensory and social enrichment efforts are examined with specific focus on their effect on aggressive behaviour and variation in their use and efficacy. It is concluded that while inappropriate or poorly distributed enrichment may encourage aggressive competition, enrichment that is species, sex, age and background appropriate can dramatically reduce aggression, can eliminate abnormal behaviour and substantially improve the welfare of primates maintained in captivity.

  4. Biochemistry and Aggression: Psychohematological Model.

    ERIC Educational Resources Information Center

    Foster, Hilliard G., Jr.; Spitz, Reuben T.

    1994-01-01

    Examines biochemical measures in a population of forensic psychiatric inpatients. Regression equations utilizing chemical and biological variables were developed and evaluated to determine their value in predicting the severity and frequency of aggression. Findings strongly suggest the presence of specific biochemical alteration among those…

  5. Risperidone and Explosive Aggressive Autism.

    ERIC Educational Resources Information Center

    Horrigan, Joseph P.; Barnhill, L. Jarrett

    1997-01-01

    In this study, 11 males with autism and mental retardation were administered risperidone. Substantial clinical improvement was noted almost immediately; patients with aggression, self-injury, explosivity, and poor sleep hygiene were most improved. The modal dose for optimal response was 0.5 mg bid. Weight gain was a significant side effect.…

  6. Aggressive Angiomyxoma in Pregnancy: A Rare Condition, a Common Misdiagnosis.

    PubMed

    Sampaio, J; Sarmento-Gonçalves, I; Ramada, D; Amaro, T; Tiago-Silva, P

    2016-01-01

    Introduction. Aggressive angiomyxoma is a rare mesenchymal neoplasm. Although benign in the majority of the cases, these neoplasms usually present a locally infiltrative nature and high rates of recurrence. Due to its rarity, misdiagnosis is a common problem. Case Presentation. We present one case of aggressive angiomyxoma in a 25-year-old pregnant woman. The patient presented with a large vaginal mass that was interpreted as a vaginal cyst. We performed surgical resection of the neoplasm and the correct diagnosis was only achieved after histological examination. With this case, we highlight the importance of considering this diagnosis in patients with genital and perineal masses of unknown origin and the impact of a correct preoperative diagnosis in patient's management and follow-up. Conclusion. Although aggressive angiomyxoma is rare, it should be considered in differential diagnosis of pelviperineal masses in young women. Its positivity to estrogen and progesterone receptors can justify enlargement and recurrence during pregnancy, although few cases are reported. Early recognition demands high index of suspicion for both gynaecologists and pathologists. Wide surgical excision with tumor free margins is the basis of curative treatment. Adjuvant therapy may be necessary for residual or recurrent tumors. Long-term follow-up is recommended. PMID:27274877

  7. Personal standards for judging aggression by a relationship partner: How much aggression is too much?

    PubMed

    Arriaga, Ximena B; Capezza, Nicole M; Daly, Christine A

    2016-01-01

    What determines whether people tolerate partner aggression? This research examined how norms, relationship experiences, and commitment predict personal standards for judging aggressive acts by a partner. Studies 1a and 1b (n = 689) revealed that experiencing aggression in a current relationship and greater commitment predicted greater tolerance for common partner aggression. Study 2 longitudinally tracked individuals who had never experienced partner aggression (n = 52). Once aggression occurred, individuals adopted more tolerant standards, but only if they were highly committed. Study 3 involved experimentally manipulating the relevance of partner aggression among individuals who reported current partner aggression (n = 73); they were more tolerant of aggressive acts imagined to occur by their partner (vs. the same acts by a stranger), but only if they were highly committed. Personal standards for judging partner aggression are dynamic. They shift toward greater tolerance when committed people experience aggression in a current relationship.

  8. Parotid area lymph node metastases from preliminarily diagnosed patients with nasopharyngeal carcinoma: report on tumor characteristics and oncologic outcomes

    PubMed Central

    Xiao, Youping; Zong, Jingfeng; Qiu, Sufang; Bai, Penggang; Dai, Yitao; Zhou, Lin; Chen, Xiaolin; Zheng, Wei; Chen, Yunbin; Lin, Shaojun; Pan, Jianji

    2016-01-01

    The parotid area lymph node (PLN) is an uncommon site of metastasis originating from nasopharyngeal carcinoma (NPC). The study aimed to investigate clinical characteristics and outcomes of patients with preliminarily diagnosed NPC with PLN metastases. Here we retrospectively reviewed Magnetic resonance imaging (MRI) scans of 2221 patients with untreated nonmetastatic NPC who received intensity-modulated radiation therapy (IMRT). Finally, 64 (2.9%) patients were identified with PLN metastases, of which, 34 received PLN-sparing IMRT and 30 received PLN-radical IMRT. We also found that 42.2% had N3 disease and 95.3% had stages III-IVb. PLN metastases on MRI were characterized by ipsilateral retropharyngeal lymph node (RLN) or level II nodal extracapsular spread (ECS), ipsilateral giant cervical nodes, ipsilateral parapharyngeal extension, or solitary parotid metastasis. The 5-year overall survival, distant metastasis-free survival, regional relapse-free survival, and parotid relapse-free survival rates were 70.4%, 64.3%, 76.7%, and 87.9%, respectively. Distant metastases were the main cause of treatment failure and death. Using PLN-sparing IMRT, sparing PLN with minimal axial diameter of <10 mm, could increase the risk of parotid recurrence. However, it was not an independent prognostic factor. N classification and concurrent-based chemotherapy were almost statistically significant for distant failure and death. Overall, we demonstrated that the PLN metastases might be derived from RLN or level II nodal ECS, giant cervical nodes in a retrograde fashion, or parapharyngeal extension. Sparing PLN of <10 mm by IMRT should consider the risk of parotid recurrence. Distant metastases remained the dominant treatment failure. Further effective systemic chemotherapy should be explored. PMID:26934439

  9. Changes in the functional characteristics of tumor and normal cells after treatment with extracts of white dead-nettle

    PubMed Central

    Veleva, Ralitsa; Petkova, Bela; Moskova-Doumanova, Veselina; Doumanov, Jordan; Dimitrova, Milena; Koleva, Petya; Mladenova, Kirilka; Petrova, Svetla; Yordanova, Zhenya; Kapchina-Toteva, Veneta; Topouzova-Hristova, Tanya

    2015-01-01

    Lamium album L. is a perennial herb widely used in folk medicine. It possesses a wide spectrum of therapeutic activities (anti-inflammatory, astringent, antiseptic, antibiotic, antispasmodic, antioxidant and anti-proliferative). Preservation of medicinal plant could be done by in vitro propagation to avoid depletion from their natural habitat. It is important to know whether extracts from L. album plants grown in vitro possess similar properties as extracts from plants grown in vivo. For these reasons, it is important to examine changes in the composition of secondary metabolites during in vitro cultivation of the plant and how they affect the biological activity. We used A549 human cancer cell line and normal kidney epithelial cells MDCKII (Madin–Darby canine kidney cells II) as controls in assessing the anti-cancer effect of plant extracts. To elucidate changes in some key functional characteristics, adhesion test, MTT (3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyl tetrazolium bromide), transepithelial resistance (TER), immunofluorescence staining and trypan blue exclusion test were performed. Methanol and chloroform extracts of in vivo and in vitro propagated plants affected differently cancerous and non-cancerous cells. The most pronounced differences were observed in the morphological analysis and in the cell adhesive properties. We also detected suppressed epithelial transmembrane electrical resistance of MDCK II cells, by treatment with plant extracts, compared to non-treated MDCK II cells. A549 cells did not polarize under the same conditions. Altered organization of actin filaments in both cell types were noticed suggesting that extracts from L. album L. change TER and actin filaments, and somehow may block cell mechanisms, leading to the polarization of MDCK II cells. PMID:26019631

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

    PubMed

    Ireland, Jane L; 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 behaviour (DIPC-R) and aggression disposition (AQ). It was predicted that dispositional aggression would be predicted by implicit cognitive aggression, and that implicit cognitive aggression would predict current engagement in aggressive behaviour. It was also predicted that more impulsive implicit cognitive processing would associate with aggressive behaviour whereas cognitively effortful implicit cognitive processing would not. Implicit aggressive cognitive processing was associated with increased dispositional aggression but not current reports of aggressive behaviour. Impulsive implicit cognitive processing of an aggressive nature predicted increased dispositional aggression whereas more cognitively effortful implicit cognitive aggression did not. The article concludes by outlining the importance of accounting for implicit cognitive processing among prisoners and the need to separate such processing into facets (i.e. impulsive vs. cognitively effortful). Implications for future research and practice in this novel area of study are indicated.

  11. Husbands' and Wives' Marital Adjustment, Verbal Aggression, and Physical Aggression as Longitudinal Predictors of Physical Aggression in Early Marriage

    ERIC Educational Resources Information Center

    Schumacher, Julie A.; Leonard, Kenneth E.

    2005-01-01

    Marital adjustment, verbal aggression, and physical aggression have long been associated in the marital literature, but the nature of their associations remains unclear. In this study, the authors examined these 3 constructs as risk factors for physical aggression during the first 2 years of marriage in 634 couples recruited as they applied for…

  12. Molecular Targeted Therapies of Aggressive Thyroid Cancer

    PubMed Central

    Ferrari, Silvia Martina; Fallahi, Poupak; Politti, Ugo; Materazzi, Gabriele; Baldini, Enke; Ulisse, Salvatore; Miccoli, Paolo; Antonelli, Alessandro

    2015-01-01

    Differentiated thyroid carcinomas (DTCs) 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 toward the development of new drugs. Several genetic alterations in different molecular pathways in TC have been shown in the past few 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 aforementioned 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, 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 the therapy in

  13. Impact of metabolic heterogeneity on tumor growth, invasion, and treatment outcomes

    PubMed Central

    Robertson-Tessi, Mark; Gillies, Robert J; Gatenby, Robert A; Anderson, Alexander RA

    2015-01-01

    Histopathological knowledge that extensive heterogeneity exists between and within tumors has been confirmed and deepened recently by molecular studies. However, the impact of tumor heterogeneity on prognosis and treatment remains as poorly understood as ever. Using a hybrid multi-scale mathematical model of tumor growth in vascularized tissue, we investigated the selection pressures exerted by spatial and temporal variations in tumor microenvironment and the resulting phenotypic adaptations. A key component of this model is normal and tumor metabolism and its interaction with microenvironmental factors. The metabolic phenotype of tumor cells is plastic, and microenvironmental selection leads to increased tumor glycolysis and decreased pH. Once this phenotype emerges, the tumor dramatically changes its behavior due to acid-mediated invasion, an effect that depends on both variations in the tumor cell phenotypes and their spatial distribution within the tumor. In early stages of growth, tumors are stratified, with the most aggressive cells developing within the interior of the tumor. These cells then grow to the edge of the tumor and invade into the normal tissue using acidosis. Simulations suggest that diffusible cytotoxic treatments such as chemotherapy may increase the metabolic aggressiveness of a tumor due to drug-mediated selection. Chemotherapy removes the metabolic stratification of the tumor and allows more aggressive cells to grow towards blood vessels and normal tissue. Anti-angiogenic therapy also selects for aggressive phenotypes due to degradation of the tumor microenvironment, ultimately resulting in a more invasive tumor. In contrast, pH buffer therapy slows down the development of aggressive tumors, but only if administered when the tumor is still stratified. Overall, findings from this model highlight the risks of cytotoxic and anti-angiogenic treatments in the context of tumor heterogeneity resulting from a selection for more aggressive behaviors

  14. Kidney cancer progression linked to shifts in tumor metabolism

    Cancer.gov

    Investigators in The Cancer Genome Atlas Research Network have uncovered a connection between how tumor cells use energy from metabolic processes and the aggressiveness of the most common form of kidney cancer, clear cell renal cell carcinoma.

  15. Aggression as positive reinforcement in mice under various ratio- and time-based reinforcement schedules.

    PubMed

    May, Michael E; Kennedy, Craig H

    2009-03-01

    There is evidence suggesting aggression may be a positive reinforcer in many species. However, only a few studies have examined the characteristics of aggression as a positive reinforcer in mice. Four types of reinforcement schedules were examined in the current experiment using male Swiss CFW albino mice in a resident-intruder model of aggression as a positive reinforcer. A nose poke response on an operant conditioning panel was reinforced under fixed-ratio (FR 8), fixed-interval (FI 5-min), progressive ratio (PR 2), or differential reinforcement of low rate behavior reinforcement schedules (DRL 40-s and DRL 80-s). In the FR conditions, nose pokes were maintained by aggression and extinguished when the aggression contingency was removed. There were long postreinforcement pauses followed by bursts of responses with short interresponse times (IRTs). In the FI conditions, nose pokes were maintained by aggression, occurred more frequently as the interval elapsed, and extinguished when the contingency was removed. In the PR conditions, nose pokes were maintained by aggression, postreinforcement pauses increased as the ratio requirement increased, and responding was extinguished when the aggression contingency was removed. In the DRL conditions, the nose poke rate decreased, while the proportional distributions of IRTs and postreinforcement pauses shifted toward longer durations as the DRL interval increased. However, most responses occurred before the minimum IRT interval elapsed, suggesting weak temporal control of behavior. Overall, the findings suggest aggression can be a positive reinforcer for nose poke responses in mice on ratio- and time-based reinforcement schedules.

  16. Violent video games stress people out and make them more aggressive.

    PubMed

    Hasan, Youssef; Bègue, Laurent; Bushman, Brad J

    2013-01-01

    It is well known that violent video games increase aggression, and that stress increases aggression. Many violent video games can be stressful because enemies are trying to kill players. The present study investigates whether violent games increase aggression by inducing stress in players. Stress was measured using cardiac coherence, defined as the synchronization of the rhythm of breathing to the rhythm of the heart. We predicted that cardiac coherence would mediate the link between exposure to violent video games and subsequent aggression. Specifically, we predicted that playing a violent video game would decrease cardiac coherence, and that cardiac coherence, in turn, would correlate negatively with aggression. Participants (N = 77) played a violent or nonviolent video game for 20 min. Cardiac coherence was measured before and during game play. After game play, participants had the opportunity to blast a confederate with loud noise through headphones during a reaction time task. The intensity and duration of noise blasts given to the confederate was used to measure aggression. As expected, violent video game players had lower cardiac coherence levels and higher aggression levels than did nonviolent game players. Cardiac coherence, in turn, was negatively related to aggression. This research offers another possible reason why violent games can increase aggression-by inducing stress. Cardiac coherence can be a useful tool to measure stress induced by violent video games. Cardiac coherence has several desirable methodological features as well: it is noninvasive, stable against environmental disturbances, relatively inexpensive, not subject to demand characteristics, and easy to use. PMID:23097053

  17. AGGRESSION AS POSITIVE REINFORCEMENT IN MICE UNDER VARIOUS RATIO- AND TIME-BASED REINFORCEMENT SCHEDULES

    PubMed Central

    May, Michael E; Kennedy, Craig H

    2009-01-01

    There is evidence suggesting aggression may be a positive reinforcer in many species. However, only a few studies have examined the characteristics of aggression as a positive reinforcer in mice. Four types of reinforcement schedules were examined in the current experiment using male Swiss CFW albino mice in a resident–intruder model of aggression as a positive reinforcer. A nose poke response on an operant conditioning panel was reinforced under fixed-ratio (FR 8), fixed-interval (FI 5-min), progressive ratio (PR 2), or differential reinforcement of low rate behavior reinforcement schedules (DRL 40-s and DRL 80-s). In the FR conditions, nose pokes were maintained by aggression and extinguished when the aggression contingency was removed. There were long postreinforcement pauses followed by bursts of responses with short interresponse times (IRTs). In the FI conditions, nose pokes were maintained by aggression, occurred more frequently as the interval elapsed, and extinguished when the contingency was removed. In the PR conditions, nose pokes were maintained by aggression, postreinforcement pauses increased as the ratio requirement increased, and responding was extinguished when the aggression contingency was removed. In the DRL conditions, the nose poke rate decreased, while the proportional distributions of IRTs and postreinforcement pauses shifted toward longer durations as the DRL interval increased. However, most responses occurred before the minimum IRT interval elapsed, suggesting weak temporal control of behavior. Overall, the findings suggest aggression can be a positive reinforcer for nose poke responses in mice on ratio- and time-based reinforcement schedules. PMID:19794833

  18. Violent video games stress people out and make them more aggressive.

    PubMed

    Hasan, Youssef; Bègue, Laurent; Bushman, Brad J

    2013-01-01

    It is well known that violent video games increase aggression, and that stress increases aggression. Many violent video games can be stressful because enemies are trying to kill players. The present study investigates whether violent games increase aggression by inducing stress in players. Stress was measured using cardiac coherence, defined as the synchronization of the rhythm of breathing to the rhythm of the heart. We predicted that cardiac coherence would mediate the link between exposure to violent video games and subsequent aggression. Specifically, we predicted that playing a violent video game would decrease cardiac coherence, and that cardiac coherence, in turn, would correlate negatively with aggression. Participants (N = 77) played a violent or nonviolent video game for 20 min. Cardiac coherence was measured before and during game play. After game play, participants had the opportunity to blast a confederate with loud noise through headphones during a reaction time task. The intensity and duration of noise blasts given to the confederate was used to measure aggression. As expected, violent video game players had lower cardiac coherence levels and higher aggression levels than did nonviolent game players. Cardiac coherence, in turn, was negatively related to aggression. This research offers another possible reason why violent games can increase aggression-by inducing stress. Cardiac coherence can be a useful tool to measure stress induced by violent video games. Cardiac coherence has several desirable methodological features as well: it is noninvasive, stable against environmental disturbances, relatively inexpensive, not subject to demand characteristics, and easy to use.

  19. The dynamic appraisal of situational aggression: an instrument to assess risk for imminent aggression in psychiatric inpatients.

    PubMed

    Ogloff, James R P; Daffern, Michael

    2006-01-01

    Considerable research has attempted to delineate the demographic and clinical characteristics of high-risk psychiatric patients and identify salient modifiable aspects of aggression prone environments. Recently, there has also been increased interest in the development and testing of structured schemes for the assessment of risk for aggression within inpatient psychiatric settings. Although some of these methods show acceptable predictive validity, their ability to inform day-to-day treatment and management decisions is limited. The current research was designed to identify existing and novel risk factors that would assist staff to identify and manage the risk for aggression in psychiatric inpatient populations. Results showed that assessments supported by structured risk measures were more accurate than unaided clinical judgements based only on nurses' clinical experience and knowledge of the patient alone. Seven test items emerged that were maximally effective at identifying acute psychiatric patients at risk for engaging in inpatient violence within 24 hours; these items have been combined in the development of the Dynamic Appraisal of Situational Aggression. Empirical analyses and clinical experience support the efficacy of the instrument in assisting clinical staff in the identification and management of inpatient aggression.

  20. Hypoxia and Prostate Cancer Aggressiveness: A Tale With Many Endings.

    PubMed

    Fraga, Avelino; Ribeiro, Ricardo; Príncipe, Paulo; Lopes, Carlos; Medeiros, Rui

    2015-08-01

    Angiogenesis, increased glycolysis, and cellular adaptation to hypoxic microenvironment are characteristic of solid tumors, including prostate cancer. These representative features are the cornerstone of cancer biology, which are well correlated with invasion, metastasis, and lethality, as well as likely with the success of prostate cancer treatment (eg, tumor hypoxia has been associated with resistance to chemotherapy and radiotherapy). It is well established that prostate cancer cells also metabolically depend on enhanced glucose transport and glycolysis for expansion, whereas growth is contingent with neovascularization to permit diffusion of oxygen and glucose. While hypoxia inducible factor 1 alpha (HIF-1α) remains the central player, the succeeding activated molecules and pathways track distinct branches, all positively correlated with the degree of intratumoral hypoxia. Among these, the vascular endothelial growth factor axis as well as the lysyl oxidase and carbonic anhydrase IX activities are notable in prostate cancer and merit further study. Here, we demonstrate their linkage with HIF-1α as a tentative explanatory mechanism of prostate cancer aggressiveness. Hypoxia drives a tale where HIF-1α-dependent effects lead to many influences in distinct key cancer biology features, rendering targeted therapies toward targets at the endings less efficient. The most appropriate approach will be to inhibit the upstream common driver (HIF-1α) activity. Additional translational and clinical research initiatives in prostate cancer are required to prove its usefulness.

  1. SU-C-BRE-05: PTV Margin Determination Based On Tumor Radiobiological Characteristics and Geometric Uncertainties Derived From Daily Cone- Beam CT Images

    SciTech Connect

    Selvaraj, J

    2014-06-15

    Purpose: To determine required PTV margins for ≤1% loss in mean population TCP using systematic (Σ) and random (σ) errors calculated from daily cone-beam CT (CBCT) images of head and neck patients. Methods: Daily CBCT images were acquired for 50 head and neck patients. The CBCT image sets acquired at each fraction were registered with planning CT to obtain positional errors for each patient for each fraction. Systematic and random errors were calculated from data collected for 50 patients as described in IPEM On Target report. CTV delineation uncertainty of 2mm is added quadratically to systematic error. Assuming a spherical target volume, the dose in each voxel of target volume is summed for each fraction in the treatment by shifting the dose grid to calculate mean population TCP inclusive of geometric uncertainties using a Monte Carlo method. These simulations were repeated for the set of Σ and σ in each axis for different PTV margins and drop in TCP for each margin are obtained. In order to study the effect of dose-response curve on PTV margins, two different σα of 0.048 Gy-1 and 0.218 Gy-1 representing steep and shallow dose-response curves are studied. Σ were 2.5, 2.5, 2.1 mm and σ were 0.3, 0.3 0.2 mm respectively in x, y and z axis respectively. Results: PTV margins based on tumor radiobiological characteristics are 4.8, 4.8 and 4 mm in x, y and z axis assuming 25 treatment fractions for σα 0.048 Gy-1 (steep) and 4.2,4.2 and 2.2 for σα of 0.218 Gy-1 (shallow). While the TCP-based margins did not differ much in x and y axis, it is considerably smaller in z axis for shallow DRC. Conclusion: TCP based margins are substantially smaller than physical dose-based margin recipes. This study also demonstrates the importance of considering tumor radiobiological characteristics while deriving margins.

  2. Pre-Clinical Mouse Models of Primary and Metastatic Pleural Cancers of the Lung and Breast and the Use of Bioluminescent Imaging to Monitor Pleural Tumor Burden (ms#CP-10-0176)

    PubMed Central

    Servais, Elliot L.; Colovos, Christos; Kachala, Stefan S.; Adusumilli, Prasad S.

    2015-01-01

    Malignant pleural disease (MPD) results in an estimated 150,000 cases of malignant pleural effusions (MPE) annually. The most common malignancies associated with MPD are primary malignant pleural mesothelioma (MPM) and metastatic lung cancer, breast cancer and lymphoma. MPM is a rare, regionally aggressive, malignancy whose incidence is increasing secondary to the latency of disease progression. MPD is characteristic of advanced stage pleural disease and portends a grave clinical prognosis with a median survival between 3 to 12 months. Treatment for MPD is primarily palliative by thoracentesis to drain the effusion or surgical procedures to liberate trapped lung and obliterate cavities in order to limit subsequent collection of pleural effusions. Systemic chemotherapy is typically ineffective due to dose-limiting toxicities and poor intratumoral penetration. Preclinical investigations conducted in flank and intraperitoneal tumor models do not fully recapitulate the pleural tumor microenvironment and the results are not directly translational to the clinically setting. An orthotopic model of pleural malignancy allows investigators to evaluate the efficacy of therapies against novel molecular targets in a microenvironment that mimics the clinical tumor milieu. The protocol described herein provides a mouse model of MPM and MPD from non-hematogenous tumors resulting in reproducible tumor location, tumor progression, animal survival, and histopathology. Pleural tumor growth in this model resembles the regionally aggressive clinical course and tumor microenvironment of human pleural cancers and provides an optimal animal model to investigate MPD biology and therapies. PMID:21898334

  3. When Violence Pays: A Cost-Benefit Analysis of Aggressive Behavior in Animals and Humans

    PubMed Central

    Georgiev, Alexander V.; Klimczuk, Amanda C. E.; Traficonte, Daniel M.

    2013-01-01

    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. PMID:23864299

  4. Prevalence and management of gastrointestinal stromal tumors.

    PubMed

    Machado-Aranda, David; Malamet, Matthew; Chang, Yeon-Jeen; Jacobs, Michael J; Ferguson, Lorenzo; Silapaswan, Sumet; Goriel, Yousif; Kolachalam, R; Mittal, Vijay K

    2009-01-01

    The prevalence and characteristics of patients with confirmed gastrointestinal stromal tumor (GIST) in a community hospital over a 6-year period are described. Our objective was to communicate our experience managing this rare tumor of the gastrointestinal tract. A retrospective chart review was performed. Patients were selected based on International Classification of Diseases, 9th Revision codes in correlation with their respective confirmational pathology. Patients with a diagnosis of GIST, cells of Cajal tumor, and/or different varieties of gastrointestinal sarcoma were included in this study. These tumors had to have a positive C-kit on immunohistochemistry. Demographic and clinical data were collected from medical records as well as pathology reports. Follow up from attendings' office records and telephone interviews complemented our data. A total of 61 patients was identified in our institution (averaging 10 patients per year). Females represented 63 per cent of our series. The average ages were 70.2 +/- 19.1 years for females and 59.4 +/- 13.5 years for males (P < 0.01). The most common clinical presentation was an intra-abdominal nonobstructing mass followed by an endoscopically detected mass or incidental tumors found during unrelated surgery. Surgical emergencies such as acute abdomen and gastrointestinal bleed were rare. Over half of these tumors were located in the stomach. Other sites were the small intestine, colon, esophagus, and rectal-vaginal septum. Opened surgical resection was performed in two-thirds of treated cases, whereas laparoscopic resection was done in the remainder. Only 18 per cent of these tumors were considered benign, whereas 35 per cent were considered to have some malignant potential and 47 per cent were of undetermined potential. In surgically resected tumors, we found a 42 per cent recurrence rate with a median average time of recurrence of 22 months. Pathologic grading and type of surgery were not predictors of rate and timing

  5. Relational Aggression among Middle School Girls

    ERIC Educational Resources Information Center

    Dallape, Aprille

    2008-01-01

    The purpose of this study was to examine the correlates that define relational aggression among middle school girls, the relationships among these factors, and the association between the correlates of relational aggression and the type of relational aggression (e.g., verbal, withdrawal) exhibited among middle school girls. The findings of this…

  6. Aggression induced by intermittent positive reinforcement.

    PubMed

    Looney, T A; Cohen, P S

    1982-01-01

    Mammalian and non-mammalian species engage in aggressive behavior toward animate and inanimate targets when exposed to intermittent access to a positive reinforcer. This behavior, called extinction- or schedule-induced aggression, typically includes a biting or striking topography that inflicts damage on a target. This paper critically reviews research and theoretical issues concerning such aggression and suggests directions for future investigation.

  7. Treating Comorbid Anxiety and Aggression in Children

    ERIC Educational Resources Information Center

    Levy, Karyn; Hunt, Caroline; Heriot, Sandra

    2007-01-01

    Objective: The aim of the study was to evaluate the effectiveness of an intervention that targeted both anxious and aggressive behaviors in children with anxiety disorders and comorbid aggression by parent report. Method: The effects of a cognitive-behavioral therapy intervention targeting comorbid anxiety and aggression problems were compared…

  8. Down-regulation of both p21/Cip1 and p27/Kip1 produces a more aggressive prostate cancer phenotype

    PubMed Central

    Roy, Srirupa; Singh, Rana P.; Agarwal, Chapla; Siriwardana, Sunitha; Sclafani, Robert; Agarwal, Rajesh

    2009-01-01

    Roles of cyclin dependent kinase inhibitors, p21/Cip1 (p21) and p27/Kip1 (p27) in prostate cancer (PCa) progression is still not clear. Lower p27 protein expression in PCa tissues is often associated with poor prognosis, but prognostic significance of p21 is still controversial. Herein, we investigated the role of these molecules in determining PCa growth characteristics. We generated human PCa DU145 cell variants with knocked down levels of p21 (DU-p21) or p27 (DU-p27), or both (DU-p21+p27) via retroviral transduction of respective shRNAs and compared their various characteristics with empty vector-transduced DU145 (DU-EV) cells in vitro as well as in vivo. Knocking down either p21 or p27 did not show any significant change in doubling time, clonogenicity and cell cycle progression in DU145 cells, but simultaneous knock-down of both p21 and p27 significantly enhanced these parameters. In athymic mice, DU-p21+p27 tumors showed higher growth rate than the comparable growth of DU-EV, DU-p21 and DU-p27 tumors. Concurrently, DU-p21+p27 tumors had significantly higher proliferation rate, showing 54% and 48% increase in proliferating cell nuclear antigen (PCNA) and Ki-67-positive cells, respectively, compared to DU-EV tumors. DU-p21+p27 tumors also showed higher microvessel density and increased expression of vascular endothelial growth factor (VEGF). Proliferation and angiogenic status of DU-p21 and DU-p27 tumors was comparable to DU-EV tumors. Both in vitro and in vivo results implicate that p21 and p27 have compensatory roles in advanced prostate cancer cells, and ablation or down-modulation of both these molecules essentially enhances the aggressive prostate carcinoma phenotype. PMID:18583941

  9. Normative Beliefs and Relational Aggression: An Investigation of the Cognitive Bases of Adolescent Aggressive Behavior

    ERIC Educational Resources Information Center

    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…

  10. Social Aggression on Television and Its Relationship to Children's Aggression in the Classroom

    ERIC Educational Resources Information Center

    Martins, Nicole; Wilson, Barbara J.

    2012-01-01

    A survey was conducted with over 500 children in grades K-5 to examine whether exposure to socially aggressive content was related to children's use of social aggression. The results of the survey revealed a significant relationship between exposure to televised social aggression and increased social aggression at school, but only for girls and…

  11. [New surgical treatment options for bone tumors].

    PubMed

    Andreou, D; Henrichs, M P; Gosheger, G; Nottrott, M; Streitbürger, A; Hardes, J

    2014-11-01

    Primary bone neoplasms can be classified into benign, locally/aggressive and rarely metastasizing and malignant tumors. Patients with benign tumors usually undergo surgical treatment in cases of local symptoms, mainly consisting of pain or functional deficits due to compression of important anatomical structures, such as nerves or blood vessels. Locally/aggressive and rarely metastasizing tumors exhibit an infiltrative growth pattern, so that surgical treatment is necessary to prevent further destruction of bone leading to local instability. Finally, the surgical treatment of malignant tumors is, with few exceptions, considered to be a prerequisite for long-term survival, either alone or in combination with systemic chemotherapy. Whereas the main objective of surgery in the treatment of benign tumors is relief of local symptoms with a minimum amount of damage to healthy tissue and minimizing the risk of local recurrence while ensuring bone stability in locally aggressive and rarely metastasizing tumors, the primary goal in the operative treatment of bone sarcomas is the resection of the tumor with clear surgical margins followed by defect reconstruction and the preservation of function. This review examines the current developments in the surgical treatment of primary bone neoplasms with respect to the management of the tumors and novel reconstructive options.

  12. Read anything mean lately? associations between reading aggression in books and aggressive behavior in adolescents.

    PubMed

    Stockdale, Laura A; Coyne, Sarah M; Nelson, David A; Padilla-Walker, Laura M

    2013-01-01

    Although there have been hundreds of studies on media violence, few have focused on literature, with none examining novels. Accordingly, the aim of the current study was to examine whether reading physical and relational aggression in books was associated with aggressive behavior in adolescents. Participants consisted of 223 adolescents who completed a variety of measures detailing their media use and aggressive behavior. A non-recursive structural equation model revealed that reading aggression in books was positively associated with aggressive behavior, even after controlling for exposure to aggression in other forms of media. Associations were only found for congruent forms of aggression. Implications regarding books as a form of media are discussed.

  13. Embryonic and tumorigenic pathways converge via Nodal signaling: role in melanoma aggressiveness.

    PubMed

    Topczewska, Jolanta M; Postovit, Lynne-Marie; Margaryan, Naira V; Sam, Anthony; Hess, Angela R; Wheaton, William W; Nickoloff, Brian J; Topczewski, Jacek; Hendrix, Mary J C

    2006-08-01

    Bidirectional cellular communication is integral to both cancer progression and embryological development. In addition, aggressive tumor cells are phenotypically plastic, sharing many properties with embryonic cells. Owing to the similarities between these two types of cells, the developing zebrafish can be used as a biosensor for tumor-derived signals. Using this system, we show that aggressive melanoma cells secrete Nodal (a potent embryonic morphogen) and consequently can induce ectopic formation of the embryonic axis. We further show that Nodal is present in human metastatic tumors, but not in normal skin, and thus may be involved in melanoma pathogenesis. Inhibition of Nodal signaling reduces melanoma cell invasiveness, colony formation and tumorigenicity. Nodal inhibition also promotes the reversion of melanoma cells toward a melanocytic phenotype. These data suggest that Nodal signaling has a key role in melanoma cell plasticity and tumorigenicity, thereby providing a previously unknown molecular target for regulating tumor progression. PMID:16892036

  14. Molecular Profiling of Aggressive Lymphomas

    PubMed Central

    Rossi, Maura; Laginestra, Maria Antonella; Gazzola, Anna; Sapienza, Maria Rosaria; Pileri, Stefano A.; Piccaluga, Pier Paolo

    2012-01-01

    In the last years, several studies of molecular profiling of aggressive lymphomas were performed. In particular, it was shown that DLBCL can be distinguished in two different entities according to GEP. Specifically, ABC and GCB subtypes were characterized by having different pathogenetic and clinical features. In addition, it was demonstrated that DLBCLs are distinct from BL. Indeed, the latter is a unique molecular entity. However, relevant pathological differences emerged among the clinical subtypes. More recently, microRNA profiling provided further information concerning BL-DLBCL distinction as well as for their subclassification. In this paper, the authors based on their own experience and the most updated literature review, the main concept on molecular profiling of aggressive lymphomas. PMID:22190944

  15. Mapping Brain Development and Aggression

    PubMed Central

    Paus, Tomás

    2005-01-01

    Introduction This article provides an overview of the basic principles guiding research on brain-behaviour relationships in general, and as applied to studies of aggression during human development in particular. Method Key literature on magnetic resonance imaging of the structure and function of a developing brain was reviewed. Results The article begins with a brief introduction to the methodology of techniques used to map the developing brain, with a special emphasis on magnetic resonance imaging (MRI). It then reviews briefly the current knowledge of structural maturation, assessed by MRI, of the human brain during childhood and adolescence. The last part describes some of the results of neuroimaging studies aimed at identifying neural circuits involved in various aspects of aggression and social cognition. Conclusion The article concludes by discussing the potential and limitations of the neuroimaging approach in this field. PMID:19030495

  16. Homeostatic disturbances and human aggression.

    PubMed

    Naisberg, Y

    1997-04-01

    A new model on the nature of human aggression is presented. It rests on the assumption that a pre-established organismic homeostatic modification, based on a decrease in neuronal membrane electric threshold, causes neural facilitation. In turn, this influences the cut-off phenomenon, in particular, neuronal network and therefore either inherited schemata representation, or acquired engram linkage programs run inadequately. These programs adjust the response to working loads of the eight normal serial stages in the body's operational regime activity. The effect of facilitation on these programs is: (1) loss of discrimination when approaching involuntary multi-stimuli; (2) the corruption of acquired engram linkage portions used in neural networks; (3) significant reduction of the voluntary degrees of freedom of response, thus narrowing the body's operational regime activity. This results in damage to certain cognitive links from some acquired engram linkages, enhancing impulse-like program mismatches and causing a unilateral 'fight' response of an aggressive nature.

  17. Management Strategies for Aggressive Cushing's Syndrome: From Macroadenomas to Ectopics

    PubMed Central

    Pozza, Carlotta; Graziadio, Chiara; Giannetta, Elisa; Lenzi, Andrea; Isidori, Andrea M.

    2012-01-01

    Cushing's syndrome (CS) is a rare but severe clinical condition represented by an excessive endogenous cortisol secretion and hence excess circulating free cortisol, characterized by loss of the normal feedback regulation and circadian rhythm of the hypothalamic-pituitary axis due to inappropriate secretion of ACTH from a pituitary tumor (Cushing's disease, CD) or an ectopic source (ectopic ACTH secretion, EAS). The remaining causes (20%) are ACTH independent. As soon as the diagnosis is established, the therapeutic goal is the removal of the tumor. Whenever surgery is not curative, management of patients with CS requires a major effort to control hypercortisolemia and associated symptoms. A multidisciplinary approach that includes endocrinologists, neurosurgeons, oncologists, and radiotherapists should be adopted. This paper will focus on traditional and novel medical therapy for aggressive ACTH-dependent CS. Several drugs are able to reduce cortisol levels. Their mechanism of action involves blocking adrenal steroidogenesis (ketoconazole, metyrapone, aminoglutethimide, mitotane, etomidate) or inhibiting the peripheral action of cortisol through blocking its receptors (mifepristone “RU-486”). Other drugs include centrally acting agents (dopamine agonists, somatostatin receptor agonists, retinoic acid, peroxisome proliferator-activated receptor γ “PPAR-γ” ligands) and novel chemotherapeutic agents (temozolomide and tyrosine kinase inhibitors) which have a significant activity against aggressive pituitary or ectopic tumors. PMID:22934113

  18. MYCN repression of Lifeguard/FAIM2 enhances neuroblastoma aggressiveness.

    PubMed

    Planells-Ferrer, L; Urresti, J; Soriano, A; Reix, S; Murphy, D M; Ferreres, J C; Borràs, F; Gallego, S; Stallings, R L; Moubarak, R S; Segura, M F; Comella, J X

    2014-09-04

    Neuroblastoma (NBL) is the most common solid tumor in infants and accounts for 15% of all pediatric cancer deaths. Several risk factors predict NBL outcome: age at the time of diagnosis, stage, chromosome alterations and MYCN (V-Myc Avian Myelocytomatosis Viral Oncogene Neuroblastoma-Derived Homolog) amplification, which characterizes the subset of the most aggressive NBLs with an overall survival below 30%. MYCN-amplified tumors develop exceptional chemoresistance and metastatic capacity. These properties have been linked to defects in the apoptotic machinery, either by silencing components of the extrinsic apoptotic pathway (e.g. caspase-8) or by overexpression of antiapoptotic regulators (e.g. Bcl-2, Mcl-1 or FLIP). Very little is known on the implication of death receptors and their antagonists in NBL. In this work, the expression levels of several death receptor antagonists were analyzed in multiple human NBL data sets. We report that Lifeguard (LFG/FAIM2 (Fas apoptosis inhibitory molecule 2)/NMP35) is downregulated in the most aggressive and undifferentiated tumors. Intringuingly, although LFG has been initially characterized as an antiapoptotic protein, we have found a new association with NBL differentiation. Moreover, LFG repression resulted in reduced cell adhesion, increased sphere growth and enhanced migration, thus conferring a higher metastatic capacity to NBL cells. Furthermore, LFG expression was found to be directly repressed by MYCN at the transcriptional level. Our data, which support a new functional role for a hitherto undiscovered MYCN target, provide a new link between MYCN overexpression and increased NBL metastatic properties.

  19. An aggressive angiomyxoma of vulva - A rare entity - A case report

    PubMed Central

    Das, Bishnu Prasad; Baruah, Dipankar; Medhi, Kaberee Bhuyan; Talukder, Bharat

    2016-01-01

    Aggressive angiomyxoma is a rare, locally invasive mesenchymal tumor predominantly presenting in women of reproductive age and also having a moderate-to-high risk for local relapse. Hence, it needs to be differentiated from other mesenchymal tumors occurring in this region. We present here a case of a 40-year-old female presenting with a large, fleshy, pedunculated mass on the right labia majora.

  20. Neurobiology of aggression and violence.

    PubMed

    Siever, Larry J

    2008-04-01

    Acts of violence account for an estimated 1.43 million deaths worldwide annually. While violence can occur in many contexts, individual acts of aggression account for the majority of instances. In some individuals, repetitive acts of aggression are grounded in an underlying neurobiological susceptibility that is just beginning to be understood. The failure of "top-down" control systems in the prefrontal cortex to modulate aggressive acts that are triggered by anger provoking stimuli appears to play an important role. An imbalance between prefrontal regulatory influences and hyper-responsivity of the amygdala and other limbic regions involved in affective evaluation are implicated. Insufficient serotonergic facilitation of "top-down" control, excessive catecholaminergic stimulation, and subcortical imbalances of glutamatergic/gabaminergic systems as well as pathology in neuropeptide systems involved in the regulation of affiliative behavior may contribute to abnormalities in this circuitry. Thus, pharmacological interventions such as mood stabilizers, which dampen limbic irritability, or selective serotonin reuptake inhibitors (SSRIs), which may enhance "top-down" control, as well as psychosocial interventions to develop alternative coping skills and reinforce reflective delays may be therapeutic.

  1. Lateralization of aggression in fish.

    PubMed

    Bisazza, Angelo; de Santi, Andrea

    2003-05-15

    Recent research has suggested that lateralization of aggressive behaviors could follow an homogeneous pattern among all vertebrates. A left eye/right hemisphere dominance in eliciting aggressive responses has been demonstrated for all groups of tetrapods but teleost fish for which data is lacking. Here we studied differential eye use during aggressive interactions in three species of teleosts: Gambusia holbrooki, Xenotoca eiseni and Betta splendens. In the first experiment we checked for lateralization in the use of the eyes while the subject was attacking its own mirror image. In order to confirm the results, other tests were performed on two species and eye preference was scored during attacks or displays directed toward a live rival. All three species showed a marked preference for using the right eye when attacking a mirror image or a live rival. Thus, the direction of asymmetry in fish appears the opposite to that shown by all the other groups of vertebrates. Hypotheses on the origin of the difference are discussed.

  2. Rural neighborhoods and child aggression.

    PubMed

    Bowen, Natasha K; Wretman, Christopher J

    2014-12-01

    Structural equation modeling with latent variables was used to evaluate the direct and mediated effects of a neighborhood risk factor (negative teen behaviors) on the parent-report aggressive behavior of 213 students in grades 3 through 5 attending a school in a low-income, rural community. Contagion and social control hypotheses were examined as well as hypotheses about whether the neighborhood served as a microsystem or exosystem for rural pre-adolescents. Analyses took into account the clustering of students and ordinal nature of the data. Findings suggest that rural neighborhoods may operate as both a microsystem and exosystem for children, with direct contagion effects on their aggressive behaviors as well as indirect social control effects through parenting practices. Direct effects on aggression were also found for parenting practices and child reports of friends' negative behaviors. Pre-adolescence may be a transitional stage, when influences of the neighborhood on child behavior begin to compete with influences of caregivers. Findings can inform the timing and targets of violence prevention in rural communities.

  3. Lateralization of aggression in fish.

    PubMed

    Bisazza, Angelo; de Santi, Andrea

    2003-05-15

    Recent research has suggested that lateralization of aggressive behaviors could follow an homogeneous pattern among all vertebrates. A left eye/right hemisphere dominance in eliciting aggressive responses has been demonstrated for all groups of tetrapods but teleost fish for which data is lacking. Here we studied differential eye use during aggressive interactions in three species of teleosts: Gambusia holbrooki, Xenotoca eiseni and Betta splendens. In the first experiment we checked for lateralization in the use of the eyes while the subject was attacking its own mirror image. In order to confirm the results, other tests were performed on two species and eye preference was scored during attacks or displays directed toward a live rival. All three species showed a marked preference for using the right eye when attacking a mirror image or a live rival. Thus, the direction of asymmetry in fish appears the opposite to that shown by all the other groups of vertebrates. Hypotheses on the origin of the difference are discussed. PMID:12742249

  4. Neighborhood as a predictor of non-aggressive, but not aggressive, antisocial behaviors in adulthood

    PubMed Central

    Burt, S. Alexandra; Klump, Kelly L.; Kashy, Deborah A.; Gorman-Smith, Deborah; Neiderhiser, Jenae M.

    2015-01-01

    Background Prior meta-analytic work has highlighted important etiological distinctions between aggressive (AGG) and non-aggressive rule-breaking (RB) dimensions of antisocial behavior. Among these is the finding that RB is influenced by the environment more than is AGG. Relatively little research, however, has sought to identify the specific environmental experiences that contribute to this effect. Method The current study examined whether adults residing in the same neighborhood (N = 1,915 participants in 501 neighborhoods) were more similar in their AGG and RB than would be expected by chance. Analyses focused on simple multi-level models, with the participant as the lower-level unit and the neighborhood as the upper-level unit. Results Results revealed little-to-no evidence of neighborhood-level variance in AGG. By contrast, 11+% of the variance in RB could be predicted from participant neighborhood, results that persisted even when considering the possibility of genetic relatedness across participants and neighborhood selection effects. Moreover, 17% of this neighborhood-level variance in RB was accounted for by neighborhood structural characteristics and social processes. Discussion Findings bolster prior suggestions that broader contextual experiences, like the structural and social characteristics of one's neighborhood, contribute in a meaningful way to RB in particular. Our results also tentatively imply that this association may be environmental in origin. Future work should seek to develop additional, stronger designs capable of more clearly leveraging genetic un-relatedness to improve causal inferences regarding the environment. PMID:26040779

  5. [Pharmacological treatment of syndromes of aggressivity].

    PubMed

    Itil, T M

    1978-01-01

    In the treatment of violent-aggressive behavior, four major groups of drugs emerged: 1. Major tranquilizers in the treatment of aggressive-violent behavior associated with psychotic syndromes. 2. Anti-epileptic drugs such as diphenylhydantoin and barbiturates in the treatment of aggressive-violent behavior within the epileptic syndrome. 3. Psychostimulants in the treatment of aggressive behavior of adolescents and children within behavior disturbances. 4. Anti-male hormones such as cyproterone acetate in the treatment of violent-aggressive behavior associated with pathological sexual hyperactivity. Whereas each category of drug is predominantly effective in one type of aggressive syndrome, it may also be effective in other conditions as well. Aggression as a result of a personality disorder is most difficult to treat with drugs. PMID:34189

  6. [Pharmacological treatment of syndromes of aggressivity].

    PubMed

    Itil, T M

    1978-01-01

    In the treatment of violent-aggressive behavior, four major groups of drugs emerged: 1. Major tranquilizers in the treatment of aggressive-violent behavior associated with psychotic syndromes. 2. Anti-epileptic drugs such as diphenylhydantoin and barbiturates in the treatment of aggressive-violent behavior within the epileptic syndrome. 3. Psychostimulants in the treatment of aggressive behavior of adolescents and children within behavior disturbances. 4. Anti-male hormones such as cyproterone acetate in the treatment of violent-aggressive behavior associated with pathological sexual hyperactivity. Whereas each category of drug is predominantly effective in one type of aggressive syndrome, it may also be effective in other conditions as well. Aggression as a result of a personality disorder is most difficult to treat with drugs.

  7. A meta-analysis of the distinction between reactive and proactive aggression in children and adolescents.

    PubMed

    Polman, Hanneke; Orobio de Castro, Bram; Koops, Willem; van Boxtel, Herman W; Merk, Welmoet W

    2007-08-01

    The present meta-analytic review aimed to clarify divergent findings concerning the relation between reactive and proactive aggression in children and adolescents. Fifty-one studies with 17,965 participants were included in the analysis. A significant correlation between reactive and proactive aggression was found. The strength of this relation varied considerably between studies, from -.10 to .89. Observational assessment and tilt/noise tasks were associated with smaller correlations than questionnaires. Within the large group of questionnaire studies, studies disentangling the form and function of aggression found lower correlations than studies that did not disentangle form and function. Among questionnaire studies, higher reliability was associated with larger correlations. Effect size did not depend on other study characteristics such as sample type, age, and informant type. It is concluded that reactive and proactive aggression are most clearly distinguished with behavioral observations and questionnaires that unravel form and functions of aggression.

  8. Failure-to-thrive syndrome associated with tumor formation by Madin-Darby canine kidney cells in newborn nude mice.

    PubMed

    Brinster, Lauren R; Omeir, Romelda L; Foseh, Gideon S; Macauley, Juliete N; Snoy, Philip J; Beren, Joel J; Teferedegne, Belete; Peden, Keith; Lewis, Andrew M

    2013-08-01

    Tumors that formed in newborn nude mice that were inoculated with 10(7) Madin-Darby canine kidney (MDCK) cells were associated with a failure-to-thrive (FTT) syndrome consisting of growth retardation, lethargy, weakness, and dehydration. Scoliosis developed in 41% of affected pups. Pups were symptomatic by week 2; severely affected pups became moribund and required euthanasia within 3 to 4 wk. Mice with FTT were classified into categories of mild, moderate, and severe disease by comparing their weight with that of age-matched normal nude mice. The MDCK-induced tumors were adenocarcinomas that invaded adjacent muscle, connective tissue, and bone; 6 of the 26 pups examined had lung metastases. The induction of FTT did not correlate with cell-line aggressiveness as estimated by histopathology or the efficiency of tumor formation (tumor-forming dose 50% endpoint range = 10(2.8) to 10(7.5)); however, tumor invasion of the paravertebral muscles likely contributed to the scoliosis noted. In contrast to the effect of MDCK cells, tumor formation observed in newborn mice inoculated with highly tumorigenic, human-tumor-derived cell lines was not associated with FTT development. We suggest that tumor formation and FTT are characteristics of these MDCK cell inocula and that FTT represents a new syndrome that may be similar to the cachexia that develops in humans with cancer or other diseases. PMID:24209967

  9. Microsatellite alteration at chromosome 3p loci in neuroendocrine and non-neuroendocrine lung tumors. Histogenetic and clinical relevance.

    PubMed Central

    Hurr, K.; Kemp, B.; Silver, S. A.; el-Naggar, A. K.

    1996-01-01

    Although chromosome 3p regions are the most frequent site for genetic alterations in small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC), the extent of such abnormality in carcinoid tumors remained to be investigated. Moreover, the histogenetic and biological implications of these findings in non-carcinoid lung tumors remain unclear. We studied eight microsatellite loci on chromosome 3p regions by multiplex polymerase chain reaction in paired normal and tumor DNA from 17 carcinoid tumors, 5 SCLCs, and 38 NSCLCs to determine the histogenetic and the clinical significance of their alterations in these neoplasms. Our results revealed a lack of microsatellite abnormalities at all loci tested in both typical and atypical carcinoid tumors. SCLCs and NSCLCs showed loss of heterozygosity in 100% (5/5) and 58.0% (22/38), respectively. Loss of heterozygosity at more than two loci correlated significantly with poor histological differentiation and were preponderantly found in high proliferative index and DNA aneuploid NSCLCs. Microsatellite instability was noted in only one (1.7%) of the lesions. Our study suggests that 1) the difference in chromosome 3p alterations between carcinoid tumors and SCLCs favors a stochastic rather than linear evolution of these tumors, 2) 3p alterations may constitute an initial event in the development of small cell carcinomas, and 3) loss of heterozygosity at 3p loci is associated with aggressive tumor characteristics in non-small-cell carcinomas. Images Figure 2 PMID:8701999

  10. Distinctive pattern of let-7 family microRNAs in aggressive carcinoma of the oral tongue in young patients

    PubMed Central

    Hilly, Ohad; Pillar, Nir; Stern, Sagit; Strenov, Yulia; Bachar, Gideon; Shomron, Noam; Shpitzer, Thomas

    2016-01-01

    Oral cavity squamous cell carcinoma may be more aggressive at presentation and recurrence in young patients compared with older patients. Dysregulation of microRNAs (miRNAs or miRs) has been associated with the development and prognosis of oral cavity cancer. The present study investigated miRNA expression in carcinoma of the oral tongue in young patients. miRNA expression profiles were evaluated in formalin-fixed, paraffin-embedded samples of tumor and normal mucosa from 12 patients aged <30 years old with squamous cell carcinoma of the tongue. The levels of let-7f-5p, miR-30b-5p and let-7e-5p were upregulated in tumors (P<0.05). The expression of let-7f-5p was upregulated in non-aggressive tumors, while the expression of let-7e-5p was upregulated in aggressive tumors, compared with the corresponding normal tissue. Aggressive tumors had higher levels of let-7c, miR-130a-3p, miR-361-5p, miR-99a-5p, miR-29c-3p and let-7d-5p than non-aggressive tumors (P<0.05). The findings remained significant for let-7c upon false-discovery rate correction. An excellent correlation was noticed on validation of NanoString counts by quantitative polymerase chain reaction. The comparison with published findings in adults demonstrated a unique miRNA signature in young patients with aggressive disease. Aggressive oral cavity cancer in patients <30 years old is associated with a distinctive expression pattern of the let-7 family. Larger studies including direct comparison with older patients are warranted. PMID:27602107

  11. Distinctive pattern of let-7 family microRNAs in aggressive carcinoma of the oral tongue in young patients

    PubMed Central

    Hilly, Ohad; Pillar, Nir; Stern, Sagit; Strenov, Yulia; Bachar, Gideon; Shomron, Noam; Shpitzer, Thomas

    2016-01-01

    Oral cavity squamous cell carcinoma may be more aggressive at presentation and recurrence in young patients compared with older patients. Dysregulation of microRNAs (miRNAs or miRs) has been associated with the development and prognosis of oral cavity cancer. The present study investigated miRNA expression in carcinoma of the oral tongue in young patients. miRNA expression profiles were evaluated in formalin-fixed, paraffin-embedded samples of tumor and normal mucosa from 12 patients aged <30 years old with squamous cell carcinoma of the tongue. The levels of let-7f-5p, miR-30b-5p and let-7e-5p were upregulated in tumors (P<0.05). The expression of let-7f-5p was upregulated in non-aggressive tumors, while the expression of let-7e-5p was upregulated in aggressive tumors, compared with the corresponding normal tissue. Aggressive tumors had higher levels of let-7c, miR-130a-3p, miR-361-5p, miR-99a-5p, miR-29c-3p and let-7d-5p than non-aggressive tumors (P<0.05). The findings remained significant for let-7c upon false-discovery rate correction. An excellent correlation was noticed on validation of NanoString counts by quantitative polymerase chain reaction. The comparison with published findings in adults demonstrated a unique miRNA signature in young patients with aggressive disease. Aggressive oral cavity cancer in patients <30 years old is associated with a distinctive expression pattern of the let-7 family. Larger studies including direct comparison with older patients are warranted.

  12. Symplastic/pseudoanaplastic giant cell tumor of the bone

    PubMed Central

    Agaram, Narasimhan; Hwang, Sinchun; Lu, Chao; Wang, Lu; Healey, John; Hameed, Meera

    2016-01-01

    Objective Giant cell tumor of bone (GCTB) is a locally aggressive primary bone tumor. Its malignant counterpart is quite rare. Rarely, a conventional GCTB shows marked nuclear atypia, referred to as symplastic/pseudoanaplastic change, which can mimic sarcomatous transformation. Recently, somatic driver mutations of histone H3.3 exclusively in H3F3A have been described in GCTB. We report a series of 9 cases of GCTB with symplastic/pseudoanaplastic change, along with analysis of H3F3A variants. Materials and methods Nine cases of GCTB with symplastic change were identified. Clinico-radiological features, morphological features, and immunohistochemical stain for Ki-67 stain were reviewed. H3F3A variants were also analyzed using Sanger sequencing. Results Histologically, conventional giant cell tumor areas with scattered foci of markedly atypical cells were seen in all of the cases and all showed rare if any Ki-67 labeling. One patient had received denosumab treatment and another radiation therapy. Radiological features were characteristic of conventional GCTB. Mutation in H3F3A (p.Gly34Trp [G34W]) was found in 6 of the 7 cases. Clinical follow-up ranged from 6 to 208 months. Local recurrences were seen in 4 cases (44 %). Conclusions GCTB with symplastic/pseudoanaplastic change is an uncommon variant of conventional GCTB, which can mimic primary sarcoma or sarcomatous transformation. These tumors possess the same missense mutation in histone H3.3 as conventional GCTB. PMID:27020452

  13. Aggressive surgery for management of recurrent intraabdominal carcinoma.

    PubMed

    Roseman, J M; Minton, J P

    1983-06-01

    With the evolution of effective multimodality control of various tumors, the role of surgery for recurrent malignancies is emerging as significant factor in not only maintaining that control, but in permitting the possibility of late cure of certain, even advanced intraabdominal malignancies. Several patients with Stage IV colon or ovarian carcinoma were evaluated and found to benefit from such an aggressive surgical approach with the result of long term control as well as apparent clinical cure in the several instances. These possibilities are becoming increasingly significant as progress is made in the various treatment modalities for neoplastic diseases.

  14. Tumors of the salivary glands.

    PubMed

    Madani, Gitta; Beale, Timothy

    2006-12-01

    This article reviews the role of imaging in the management of tumors of the salivary glands, discussing tumor localization, extent, and, where possible, characterization. The relative benefits of the different modalities and the typical features of benign and malignant lesions are discussed for each modality. Characteristic appearances of specific tumors are highlighted.

  15. Spinal tumor

    MedlinePlus

    Tumor - spinal cord ... spinal tumors occur in the nerves of the spinal cord itself. Most often these are ependymomas and other ... gene mutations. Spinal tumors can occur: Inside the spinal cord (intramedullary) In the membranes (meninges) covering the spinal ...

  16. Moderating role of trait aggressiveness in the effects of violent media on aggression.

    PubMed

    Bushman, B J

    1995-11-01

    Three studies were conducted to test the hypothesis that high trait aggressive individuals are more affected by violent media than are low trait aggressive individuals. In Study 1, participants read film descriptions and then chose a film to watch. High trait aggressive individuals were more likely to choose a violent film to watch than were low trait aggressive individuals. In Study 2, participants reported their mood before and after the showing of a violet or nonviolent videotape. High trait aggressive individuals felt more angry after viewing the violent videotape than did low trait aggressive individuals. In Study 3, participants first viewed either a violent or a nonviolent videotape and then competed with an "opponent" on a reaction time task in which the loser received a blast of unpleasant noise. Videotape violence was more likely to increase aggression in high trait aggressive individuals than in low trait aggressive individuals.

  17. Emotional reactivity and the association between psychopathy-linked narcissism and aggression in detained adolescent boys.

    PubMed

    Muñoz Centifanti, Luna C; Kimonis, Eva R; Frick, Paul J; Aucoin, Katherine J

    2013-05-01

    Different patterns of emotional reactivity characterize proactive and reactive functions of aggressive behavior, and theory also suggests a link of both types with narcissism. How people with narcissistic traits respond emotionally to competitive scenarios could influence their aggressiveness. Participants were 85 adolescent boys from a detention center. Several indices of emotional functioning were assessed, including attentional bias to negative emotional stimuli and psychophysiological responding. In addition, we included self-report and laboratory measures of aggression and measures of psychopathy-linked narcissism, callous-unemotional traits, and impulsivity. Psychopathy-linked narcissism was uniquely related to unprovoked aggression (i.e., proactive aggression) and to heightened attention to pictures depicting others' distress. Compared with those scoring low on narcissism, those high on narcissism, who were the least physiologically reactive group, evinced greater proactive aggression, whereas those showing a pattern of coactivation (i.e., sympathetic and parasympathetic autonomic reactivity) evinced greater reactive aggression. Results are consistent with descriptions of narcissistic individuals as being hypervigilant to negative cues and exhibiting poor emotion regulation. These characteristics may lead to aggressive and violent behavior aimed at maintaining dominance over others.

  18. Emotional reactivity and the association between psychopathy-linked narcissism and aggression in detained adolescent boys.

    PubMed

    Muñoz Centifanti, Luna C; Kimonis, Eva R; Frick, Paul J; Aucoin, Katherine J

    2013-05-01

    Different patterns of emotional reactivity characterize proactive and reactive functions of aggressive behavior, and theory also suggests a link of both types with narcissism. How people with narcissistic traits respond emotionally to competitive scenarios could influence their aggressiveness. Participants were 85 adolescent boys from a detention center. Several indices of emotional functioning were assessed, including attentional bias to negative emotional stimuli and psychophysiological responding. In addition, we included self-report and laboratory measures of aggression and measures of psychopathy-linked narcissism, callous-unemotional traits, and impulsivity. Psychopathy-linked narcissism was uniquely related to unprovoked aggression (i.e., proactive aggression) and to heightened attention to pictures depicting others' distress. Compared with those scoring low on narcissism, those high on narcissism, who were the least physiologically reactive group, evinced greater proactive aggression, whereas those showing a pattern of coactivation (i.e., sympathetic and parasympathetic autonomic reactivity) evinced greater reactive aggression. Results are consistent with descriptions of narcissistic individuals as being hypervigilant to negative cues and exhibiting poor emotion regulation. These characteristics may lead to aggressive and violent behavior aimed at maintaining dominance over others. PMID:23627957

  19. Aggressive and acute periodontal diseases.

    PubMed

    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

  20. Comprehensive keratin profiling reveals different histopathogenesis of keratocystic odontogenic tumor and orthokeratinized odontogenic cyst.

    PubMed

    Aragaki, Tadanobu; Michi, Yasuyuki; Katsube, Ken-ichi; Uzawa, Narikazu; Okada, Norihiko; Akashi, Takumi; Amagasa, Teruo; Yamaguchi, Akira; Sakamoto, Kei

    2010-12-01

    Keratocystic odontogenic tumor is a cystic lesion that behaves more aggressively than other jaw cysts. One of its characteristic histologic features is a parakeratinized uniform layer of lining epithelium. A jaw cyst lined with orthokeratinized epithelium is called an orthokeratinized odontogenic cyst. These keratinized jaw cysts are thought to be separate entities, although their histopathogenesis has not been fully assessed. To better understand these lesions, we performed comprehensive immunohistochemical profiling of the keratin expression of each. Orthokeratinized odontogenic cysts expressed keratin 1, keratin 2, keratin 10, and loricrin, suggesting differentiation toward normal epidermis. Keratocystic odontogenic tumors expressed keratin 4, keratin 13, keratin 17, and keratin 19, which is a unique expression pattern reminiscent of a mucosal squamous epithelium and an epithelial appendage. In neonatal rat tooth germ, cells strongly positive for keratin 17 and keratin 19 were observed, specifically in the dental lamina, implying the origin of keratocystic odontogenic tumor. GLI2, a downstream effector of hedgehog signaling, was significantly expressed in keratocystic odontogenic tumor and basal cell carcinoma, accompanied with robust expression of keratin 17, mammalian target of rapamycin, and BCL2. The expression of these GLI2- or keratin 17-related factors was not significantly observed in orthokeratinized odontogenic cysts. These findings provide evidence to support the viewpoint that keratocystic odontogenic tumor and orthokeratinized odontogenic cyst are separate entities, and furthermore suggest their characteristic histology, pathogenesis, and biological behaviors.

  1. Clear cell variant of calcifying epithelial odontogenic tumor of maxilla: Report of a rare case.

    PubMed

    Badrashetty, Dinesh; Rangaswamy, Shruthi; Belgode, Niranjan

    2013-09-01

    The calcifying epithelial odontogenic tumor (CEOT) is a rare benign tumor of the jaws. Pindborg's tumor having clear cells is extremely rare. Twelve central lesions have been reported of which only three cases have occurred in maxilla. Clear cell variant is a distinct entity, has more aggressive biological behavior and higher chances of recurrence. Hence it is important that presence of clear cells be included in histopathological diagnosis. Here we present a rare case of clear cell CEOT having aggressive behavior.

  2. Clear cell variant of calcifying epithelial odontogenic tumor of maxilla: Report of a rare case

    PubMed Central

    Badrashetty, Dinesh; Rangaswamy, Shruthi; Belgode, Niranjan

    2013-01-01

    The calcifying epithelial odontogenic tumor (CEOT) is a rare benign tumor of the jaws. Pindborg's tumor having clear cells is extremely rare. Twelve central lesions have been reported of which only three cases have occurred in maxilla. Clear cell variant is a distinct entity, has more aggressive biological behavior and higher chances of recurrence. Hence it is important that presence of clear cells be included in histopathological diagnosis. Here we present a rare case of clear cell CEOT having aggressive behavior. PMID:24574681

  3. Multi-level risk factors and developmental assets associated with aggressive behavior in disadvantaged adolescents.

    PubMed

    Smokowski, Paul R; Guo, Shenyang; Cotter, Katie L; Evans, Caroline B R; Rose, Roderick A

    2016-01-01

    The current study examined multilevel risk factors and developmental assets on longitudinal trajectories of aggressive behavior in a diverse sample of rural adolescents. Using ecological and social capital theories, we explored the impact of positive and negative proximal processes, social capital, and contextual characteristics (i.e., school and neighborhood) on adolescent aggression. Data came from the Rural Adaptation Project, which is a 5-year longitudinal panel study of more than 4,000 middle and high school students from 40 public schools in two rural, low income counties in North Carolina. A three-level HLM model (N = 4,056 at Wave 1, 4,251 at Wave 2, and 4,256 at Wave 3) was estimated to predict factors affecting the change trajectories of aggression. Results indicated that negative proximal processes in the form of parent-adolescent conflict, friend rejection, peer pressure, delinquent friends, and school hassles were significant predictors of aggression. In addition, social capital in the form of ethnic identity, religious orientation, and school satisfaction served as buffers against aggression. Negative proximal processes were more salient predictors than positive proximal processes. School and neighborhood characteristics had a minimal impact on aggression. Overall, rates of aggression did not change significantly over the 3-year study window. Findings highlight the need to intervene in order to decrease negative interactions in the peer and parent domains. PMID:26349636

  4. Syntheses and preliminary evaluation of [(18) F]AlF-NOTA-G-TMTP1 for PET imaging of high aggressive hepatocellular carcinoma.

    PubMed

    Li, Yesen; Zhang, Deliang; Shi, Ying; Guo, Zhide; Wu, Xinying; Ren, Jian-Lin; Zhang, Xianzhong; Wu, Hua

    2016-07-01

    The goal of this study is to evaluate a new (18) F-labeled imaging agent for diagnosing high metastatic (aggressive) hepatocellular carcinoma using positron emission tomography (PET). The new (18) F-labeled imaging agent [(18) F]AlF-NOTA-G-TMTP1 was synthesized and radiolabeled with (18) F using NOTA-AlF chelation method. The tumor-targeting characteristics of [(18) F]AlF-NOTA-G-TMTP1 was assessed in HepG2, SMCC-7721, HCC97L and HCCLM3 xenografts. The total synthesis time was about 20 min with radiochemical yield of 25 ± 6%. The specific activity was about 11.1-14.8 GBq/µmol at the end of synthesis based on the amount of peptide used and the amount of radioactivity trapped on the C18 column. The log P value of [(18) F]AlF-NOTA-G-TMTP1 was -3.166 ± 0.022. [(18) F]AlF-NOTA-G-TMTP1 accumulated in SMCC-7721 and HCCLM3 tumors (high metastatic potential) in vivo and result in tumor/muscle (T/M) ratios of 4.5 ± 0.3 and 4.7 ± 0.2 (n = 4) as measured by PET at 40 min post-injection (p.i.). Meanwhile, the tumor/muscle (T/M) ratios of HepG2 and HCC97L tumors (low metastatic potential) were1.6 ± 0.3 and 1.8 ± 0.4. The tumor uptake of [(18) F]AlF-NOTA-G-TMTP1 could be inhibited 61.9% and 57.6% by unlabeled G-TMTP1 in SMCC-7721 and HCCLM3 xenografts at 40 min p.i., respectively. Furthermore, [(18) F]AlF-NOTA-G-TMTP1 showed pretty low activity in the liver and intestines in all tumor bearing mice, such in vivo distribution pattern would be advantageous for the detection of hepatic carcinoma. Overall, [(18) F]AlF-NOTA-G-TMTP1 may specifically target high metastatic or/and aggressive hepatocellular carcinoma with low background activity and, therefore, holds the potential to be used as an imaging agent for detecting tumor lesions within the liver area. Copyright © 2016 John Wiley & Sons, Ltd.

  5. How and Why Children Change in Aggression and Delinquency from Childhood to Adolescence: Moderation of Overreactive Parenting by Child Personality

    ERIC Educational Resources Information Center

    De Haan, A. D.; Prinzie, P.; Dekovic, M.

    2010-01-01

    Background: This study examines how and why children change in aggression and delinquency from age 6 to 15 years. Besides assessing the shape of the developmental trajectories of aggression and delinquency, we investigated whether child personality characteristics, parenting, and interactions between these two predict the development of…

  6. Differential Responses of Children with Varying Degrees of Reactive and Proactive Aggression to Two Forms of Psychosocial Treatment

    ERIC Educational Resources Information Center

    Wolff, Jennifer C.; Greene, Ross W.; Ollendick, Thomas H.

    2008-01-01

    This study examined differential treatment effects for children with varying degrees of reactive and proactive aggression who received one of two types of psychosocial treatments that were specifically designed to address the unique characteristics associated with these two subtypes of aggression. Forty-seven affectively dysregulated children with…

  7. Do perceived social stress and resilience influence the effects of psychopathy-linked narcissism and CU traits on adolescent aggression?

    PubMed

    Kauten, Rebecca; Barry, Christopher T; Leachman, Lacey

    2013-01-01

    The current study explored the influences of social stress and resilience on the relation between psychopathy-linked personality characteristics (i.e., narcissism, dimensions of CU traits) and aggression with the expectation that social stress would exacerbate the relation, whereas resilience would mitigate it. In a sample of 154 at-risk adolescents (ages 16-18; 84% male), contrary to expectations, high social stress attenuated the relations of narcissism and callousness with aggression. Self-reported resilience attenuated the relation between callousness and aggression. The implications for understanding the role that these moderators might play in the association between adolescent psychopathic tendencies, particularly callousness, and aggression are discussed.

  8. Behavioral treatment approaches to pathological unsocialized physical aggression in young children.

    PubMed

    Frankel, F; Simmons, J Q

    1985-07-01

    This paper presents some hypotheses regarding the motivation of pathological unsocialized physical aggression in children and also reviews behavioral treatment. Tentative leads were offered as to extrinsic and intrinsic determinants. Among the most promising of these were parent-child interactive and attributive factors, and deficits in information processing in social situations. It was hypothesized that some of these factors might not be specific to pathological unsocialized physical aggression but are characteristic of children with behavior problems. Under this hypothesis, few studies were found which employed appropriate control groups. It was also hypothesized that the study of extrinsic and intrinsic factors for pathological unsocialized physical aggression may improve the design of treatment programs.

  9. Translational science in action: Hostile attributional style and the development of aggressive behavior problems

    PubMed Central

    Dodge, Kenneth A.

    2009-01-01

    A model of the development of hostile attributional style and its role in children's aggressive behavior is proposed, based on the translation of basic science in ethology, neuroscience, social psychology, personality psychology, and developmental psychology. Theory and findings from these domains are reviewed and synthesized in the proposed model, which posits that (a) aggressive behavior and hostile attributions are universal human characteristics, (b) socialization leads to the development of benign attributions, (c) individual differences in attributional style account for differences in aggressive behavior, and (d) interventions to change attributions have the potential to alter antisocial development. Challenges for future research are described. PMID:17152401

  10. Adolescent cancer survivors’ smoking intentions are associated with aggression, attention, and smoking history

    PubMed Central

    Tyc, Vida L.; Wilson, Stephanie J.; Nelms, Jenna; Hudson, Melissa M.; Wu, Shengjie; Xiong, Xiaoping; Hinds, Pamela S.

    2011-01-01

    Introduction The present study examines behavioral and psychosocial factors associated with smoking intentions and experimentation among adolescent survivors of pediatric cancer. Methods Adolescent survivors of brain tumor and acute lymphoblastic leukemia (n=99) provided information about their smoking histories and their intentions to smoke in the future. Behavior rating scales were completed by survivors, parents, and teachers. Results Past experimentation with smoking and higher levels of self-reported aggression were associated with intentions to smoke in the future (OR=4.18, 95%CI 1.02–17.04, and OR=1.08, 95% CI 1.01–1.15, respectively), while teacher-ratings of inattention in the classroom were negatively associated with intentions to smoke (OR=0.94, 95% CI.88–.99), all p<.05. Experimentation with smoking was more likely among older survivors (OR=1.76, 95% CI 1.16–2.66, p<.01) and those whose parents had divorced (OR=4.40, 95% CI 1.21–16.06, p<.05). Discussion A concerning minority of adolescent survivors have clear intentions to smoke, a behavior that adds to their overall health risk. Smoking intentions and experimentation are important precursors to regular smoking. Prevention efforts are needed to interrupt the progression from intentions and experimentation to established smoking and nicotine dependence in this medically vulnerable population. Implications for cancer survivors Assessment of an adolescent’s history of parental divorce, past experimentation with smoking, and aggressive behavior will identify those survivors who are likely to consider smoking in the future. Screening for these characteristics will allow clinicians to be more vigilant in health promotion. PMID:20922493

  11. Orthotopic xenografts of RCC retain histological, immunophenotypic and genetic features of tumors in patients

    PubMed Central

    Grisanzio, Chiara; Seeley, Apryle; Chang, Michelle; Collins, Michael; Di Napoli, Arianna; Cheng, Su-Chun; Percy, Andrew; Beroukhim, Rameen; Signoretti, Sabina

    2013-01-01

    Renal cell carcinoma (RCC) is an aggressive malignancy with limited responsiveness to existing treatments. In vivo models of human cancer, including RCC, are critical for developing more effective therapies. Unfortunately, current RCC models do not accurately represent relevant properties of the human disease. The goal of this study was to develop clinically relevant animal models of RCC for preclinical investigations. We transplanted intact human tumor tissue fragments orthotopically in immunodeficient mice. The xenografts were validated by comparing the morphologic, phenotypic, and genetic characteristics of the kidney tumor tissues before and after implantation. Twenty kidney tumors were transplanted into mice. Successful tumor growth was detected in 19 cases (95%). The histopathologic and immunophenotypic features of the xenografts and those of the original tumors largely overlapped in all the cases. Evaluation of genetic alterations in a subset of 10 cases demonstrated that the grafts largely retained the genetic features of the pre-implantation RCC tissues. Indeed, primary tumors and corresponding grafts displayed identical VHL mutations. Moreover, an identical pattern of DNA copy amplification or loss was observed in 6 of 10 cases (60%). In summary, orthotopic engrafting of RCC tissue fragments can be successfully used to generate animal models that closely resemble RCC in patients. These models will be invaluable for in vivo preclinical drug testing, and for deeper understanding of kidney carcinogenesis. PMID:21710693

  12. Inhibition of tumor growth by elimination of granulocytes

    PubMed Central

    1995-01-01

    As observed for many types of cancers, heritable variants of ultraviolet light-induced tumors often grow more aggressively than the parental tumors. The aggressive growth of some variants is due to the loss of a T cell-recognized tumor-specific antigen; however, other variants retain such antigens. We have analyzed an antigen retention variant and found that the variant tumor cells grow at the same rate as the parental tumor cells in vitro, but grew more rapidly than the parental cells in the T cell-deficient host. The growth of the variant cells was stimulated in vitro by factors released from tumor-induced leukocytes and by several defined growth factors. In addition, the variant cancer cells actually attracted more leukocytes in vitro than the parental cells. Furthermore, elimination of granulocytes in vivo in nude mice by a specific antigranulocyte antibody inhibited the growth of the variant cancer, indicating that this tumor requires granulocytes for rapid growth. PMID:7807024

  13. Sleep deprivation suppresses aggression in Drosophila

    PubMed Central

    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

  14. Studying aggression in Drosophila (fruit flies).

    PubMed

    Mundiyanapurath, Sibu; Certel, Sarah; Kravitz, Edward A

    2007-01-01

    Aggression is an innate behavior that evolved in the framework of defending or obtaining resources. This complex social behavior is influenced by genetic, hormonal and environmental factors. In many organisms, aggression is critical to survival but controlling and suppressing aggression in distinct contexts also has become increasingly important. In recent years, invertebrates have become increasingly useful as model systems for investigating the genetic and systems biological basis of complex social behavior. This is in part due to the diverse repertoire of behaviors exhibited by these organisms. In the accompanying video, we outline a method for analyzing aggression in Drosophila whose design encompasses important eco-ethological constraints. Details include steps for: making a fighting chamber; isolating and painting flies; adding flies to the fight chamber; and video taping fights. This approach is currently being used to identify candidate genes important in aggression and in elaborating the neuronal circuitry that underlies the output of aggression and other social behaviors.

  15. Sleep deprivation suppresses aggression in Drosophila.

    PubMed

    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.

  16. Sleep deprivation suppresses aggression in Drosophila.

    PubMed

    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. PMID:26216041

  17. Pathologic features of aggressive vulvar carcinoma are associated with epithelial-mesenchymal transition.

    PubMed

    Holthoff, Emily R; Spencer, Horace; Kelly, Thomas; Post, Steven R; Quick, Charles M

    2016-10-01

    Factors contributing to aggressive behavior in vulvar squamous cell carcinoma (vSCC) are poorly defined; however, a recent study has shown that vSCCs with an infiltrative pattern of invasion and fibromyxoid stroma are associated with worse outcomes than tumors with a pushing or nested pattern of invasion and lymphoplasmacytic stroma. Epithelial-mesenchymal transition (EMT) has been associated with tumor progression in a number of malignancies, and this study proposes that EMT contributes to tumor aggressiveness in this subset of vSCC. Immunohistochemistry was used to detect nuclear localization of β-catenin, loss of E-cadherin, and presence of vimentin in 58 cases of vSCC. The association of these phenotypic changes with pathologic features and clinical outcomes was tested using Fisher's exact and χ(2) analyses (significance at P≤.05). EMT-associated features were identified in 45 of 58 cases (78%) with 28 cases exhibiting more than one feature. Nuclear β-catenin and presence of vimentin were significantly more likely to occur in tumors with an infiltrative pattern of invasion or a fibromyxoid stromal response. Loss of E-cadherin was significantly associated with an infiltrative pattern, but not a fibromyxoid stroma. Risk for tumor recurrence was significantly increased in tumors with nuclear localization of β-catenin alone or in tumors displaying multiple EMT-associated features. These results suggest that the development of EMT may be a mechanism by which infiltrative vulvar tumors with a fibromyxoid stromal response behave more aggressively and convey worse outcomes than tumors that do not exhibit these pathologic features.

  18. Image based modeling of tumor growth.

    PubMed

    Meghdadi, N; Soltani, M; Niroomand-Oscuii, H; Ghalichi, F

    2016-09-01

    Tumors are a main cause of morbidity and mortality worldwide. Despite the efforts of the clinical and research communities, little has been achieved in the past decades in terms of improving the treatment of aggressive tumors. Understanding the underlying mechanism of tumor growth and evaluating the effects of different therapies are valuable steps in predicting the survival time and improving the patients' quality of life. Several studies have been devoted to tumor growth modeling at different levels to improve the clinical outcome by predicting the results of specific treatments. Recent studies have proposed patient-specific models using clinical data usually obtained from clinical images and evaluating the effects of various therapies. The aim of this review is to highlight the imaging role in tumor growth modeling and provide a worthwhile reference for biomedical and mathematical researchers with respect to tumor modeling using the clinical data to develop personalized models of tumor growth and evaluating the effect of different therapies.

  19. Image based modeling of tumor growth.

    PubMed

    Meghdadi, N; Soltani, M; Niroomand-Oscuii, H; Ghalichi, F

    2016-09-01

    Tumors are a main cause of morbidity and mortality worldwide. Despite the efforts of the clinical and research communities, little has been achieved in the past decades in terms of improving the treatment of aggressive tumors. Understanding the underlying mechanism of tumor growth and evaluating the effects of different therapies are valuable steps in predicting the survival time and improving the patients' quality of life. Several studies have been devoted to tumor growth modeling at different levels to improve the clinical outcome by predicting the results of specific treatments. Recent studies have proposed patient-specific models using clinical data usually obtained from clinical images and evaluating the effects of various therapies. The aim of this review is to highlight the imaging role in tumor growth modeling and provide a worthwhile reference for biomedical and mathematical researchers with respect to tumor modeling using the clinical data to develop personalized models of tumor growth and evaluating the effect of different therapies. PMID:27596102

  20. Chromosomal translocation t(8;12) induces aberrant HMGIC expression in aggressive angiomyxoma of the vulva.

    PubMed

    Nucci, M R; Weremowicz, S; Neskey, D M; Sornberger, K; Tallini, G; Morton, C C; Quade, B J

    2001-10-01

    Benign mesenchymal neoplasms associated with rearrangements of the DNA architectural factor gene HMGIC on chromosome 12 include lipomas, uterine leiomyomata, pulmonary chondroid hamartomas, endometrial polyps, salivary gland pleomorphic adenomas, and breast fibroadenomas. Although HMGIC also has been implicated in the pathobiology of aggressive angiomyxoma of the vulva, the molecular mechanisms pertaining to this neoplasm are unclear. Tissue from a recurrent aggressive angiomyxoma was investigated by cytogenetic and expression analysis for HMGIC and HMGIY. The trypsin-Giemsa-banded karyotype showed a clonal translocation between chromosomes 8 and 12 [46,XX,t(8;12)(p12;q15)]. Fluorescence in situ hybridization (FISH) analysis with whole chromosome paint probes for chromosomes 8 and 12 excluded cryptic involvement of other chromosomes. The chromosome 12 breakpoint was mapped with two-color FISH analysis using cosmid probes at the 5' and 3' termini of HMGIC. Both cosmid probes showed hybridization to the normal chromosome 12 and the der(12) chromosome, indicating that the breakpoint was 3' (telomeric) to the gene. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed HMGIC expression in the tumor, and immunohistochemistry localized HMGIC expression to the tumor's spindle cells. Like numerous benign mesenchymal tumors, this locally aggressive tumor is associated with rearrangements near or within HMGIC, but chimeric gene formation was not required for tumorigenesis. Inappropriate expression of this DNA binding protein, however, may be important in the pathobiology of this tumor. Understanding the pathogenetic mechanism may also be helpful in developing new diagnostic tools for identifying residual disease.

  1. Rampant centrosome amplification underlies more aggressive disease course of triple negative breast cancers.

    PubMed

    Pannu, Vaishali; Mittal, Karuna; Cantuaria, Guilherme; Reid, Michelle D; Li, Xiaoxian; Donthamsetty, Shashikiran; McBride, Michelle; Klimov, Sergey; Osan, Remus; Gupta, Meenakshi V; Rida, Padmashree C G; Aneja, Ritu

    2015-04-30

    Centrosome amplification (CA), a cell-biological trait, characterizes pre-neoplastic and pre-invasive lesions and is associated with tumor aggressiveness. Recent studies suggest that CA leads to malignant transformation and promotes invasion in mammary epithelial cells. Triple negative breast cancer (TNBC), a histologically-aggressive subtype shows high recurrence, metastases, and mortality rates. Since TNBC and non-TNBC follow variable kinetics of metastatic progression, they constitute a novel test bed to explore if severity and nature of CA can distinguish them apart. We quantitatively assessed structural and numerical centrosomal aberrations for each patient sample in a large-cohort of grade-matched TNBC (n = 30) and non-TNBC (n = 98) cases employing multi-color confocal imaging. Our data establish differences in incidence and severity of CA between TNBC and non-TNBC cell lines and clinical specimens. We found strong correlation between CA and aggressiveness markers associated with metastasis in 20 pairs of grade-matched TNBC and non-TNBC specimens (p < 0.02). Time-lapse imaging of MDA-MB-231 cells harboring amplified centrosomes demonstrated enhanced migratory ability. Our study bridges a vital knowledge gap by pinpointing that CA underlies breast cancer aggressiveness. This previously unrecognized organellar inequality at the centrosome level may allow early-risk prediction and explain higher tumor aggressiveness and mortality rates in TNBC patients. PMID:25868856

  2. Video media-induced aggressiveness in children.

    PubMed

    Cardwell, Michael Steven

    2013-09-01

    Transmission of aggressive behaviors to children through modeling by adults has long been a commonly held psychological concept; however, with the advent of technological innovations during the last 30 years, video media-television, movies, video games, and the Internet-has become the primary model for transmitting aggressiveness to children. This review explores the acquisition of aggressive behaviors by children through modeling behaviors in violent video media. The impact of aggressive behaviors on the child, the family, and society is addressed. Suggestive action plans to curb this societal ill are presented.

  3. [Aggressive clients in Dutch veterinary practice].

    PubMed

    Barbonis, T S A E; Endenburg, N

    2007-05-15

    Aggressive clients seem to be becoming more common. This article describes a study in which questionnaires on client behaviour were sent to veterinary assistants and veterinarians in randomly selected practices in the Netherlands. Results showed that 26.4% of the veterinarians and 29.3% of the assistants had experienced aggressive clients in the last year. Age, experience, and sex of the veterinarian or assistant did not influence the frequency with which aggressive clients were encountered. The same was true for the type of veterinary practice (companion animals, farm animals, horses, etc). The risk of encountering aggressive clients was higher among practices in large towns and in practices with a small turnover Of the veterinarians who had encountered aggressive clients at least once in their career, 31% has taken some kind of action after the aggressive encounter Nearly a quarter (24.9%) of veterinary practices have adopted a Risk Inventarization and Evaluation (RI&E) approach to preventing client aggression and 26.6% of practices have adopted another approach. While veterinarians tend not to consider aggression a big problem, they are often open to the suggestion that more attention should be paid to aggression in veterinary practice. PMID:17578228

  4. Intimate partner aggression and women's work outcomes.

    PubMed

    LeBlanc, Manon Mireille; Barling, Julian; Turner, Nick

    2014-10-01

    Using conservation of resources theory, we examined the relationship between intimate partner aggression enacted against heterosexual women and 3 types of work-related outcomes for these women: withdrawal while at work (i.e., cognitive distraction, work neglect), withdrawal from work (i.e., partial absenteeism, intentions to quit), and performance. In Study 1, we compared withdrawal both at and from work across 3 clinically categorized groups of women (n = 50), showing that experiencing physical aggression is related to higher work neglect. We replicated and extended these findings in Study 2 using a community sample of employed women (n = 249) by considering the incremental variance explained by both physical aggression and psychological aggression on these same outcomes. Results showed that physical aggression predicted higher levels of withdrawal both at and from work, with psychological aggression predicting additional variance in partial absenteeism over and above the effects of physical aggression. Study 3 extended the model to include academic performance as an outcome in a sample of female college students (n = 122) in dating relationships. Controlling for the women's conscientiousness, psychological aggression predicted lower academic performance after accounting for the effects of physical aggression. We discuss theoretical and practical implications of these results, as well as directions for future research. PMID:25068818

  5. Aggression and coexistence in female caribou

    USGS Publications Warehouse

    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.

  6. Video media-induced aggressiveness in children.

    PubMed

    Cardwell, Michael Steven

    2013-09-01

    Transmission of aggressive behaviors to children through modeling by adults has long been a commonly held psychological concept; however, with the advent of technological innovations during the last 30 years, video media-television, movies, video games, and the Internet-has become the primary model for transmitting aggressiveness to children. This review explores the acquisition of aggressive behaviors by children through modeling behaviors in violent video media. The impact of aggressive behaviors on the child, the family, and society is addressed. Suggestive action plans to curb this societal ill are presented. PMID:24002556

  7. Neural control of aggression in Drosophila.

    PubMed

    Hoopfer, Eric D

    2016-06-01

    Like most animal species, fruit flies fight to obtain and defend resources essential to survival and reproduction. Aggressive behavior in Drosophila is genetically specified and also strongly influenced by the fly's social context, past experiences and internal states, making it an excellent framework for investigating the neural mechanisms that regulate complex social behaviors. Here, I summarize our current knowledge of the neural control of aggression in Drosophila and discuss recent advances in understanding the sensory pathways that influence the decision to fight or court, the neuromodulatory control of aggression, the neural basis by which internal states can influence both fighting and courtship, and how social experience modifies aggressive behavior. PMID:27179788

  8. Gibbon Aggression During Introductions: An International Survey.

    PubMed

    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. PMID:26963568

  9. [Motives and interpersonal functions of aggression].

    PubMed

    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. Gibbon Aggression During Introductions: An International Survey.

    PubMed

    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.

  11. Calcifying epithelial odontogenic tumor (Pindborg tumor) without calcification: A rare entity

    PubMed Central

    Kaushal, Seema; Mathur, Sandeep R; Vijay, Maneesh; Rustagi, Ankur

    2012-01-01

    The calcifying epithelial odontogenic tumor is a rare benign odontogenic tumor that was first described by Pindborg in 1955. It accounts for less than 1% of all odontogenic neoplasms. The tumor is characterized histologically by the presence of polygonal epithelial cells, calcification, and eosinophilic deposits resembling amyloid. Noncalcifying Pindborg tumor is very rare and only three cases have been documented in the English language literature so far. We present an additional case of noncalcifying Pindborg tumor and review the previously reported cases. Because noncalcifying Pindborg tumor is believed to be an aggressive variant, a definitive resection of the tumor with tumor-free surgical margins and long-term follow-up is recommended. PMID:22434947

  12. Calcifying epithelial odontogenic tumor (Pindborg tumor) without calcification: A rare entity.

    PubMed

    Kaushal, Seema; Mathur, Sandeep R; Vijay, Maneesh; Rustagi, Ankur

    2012-01-01

    The calcifying epithelial odontogenic tumor is a rare benign odontogenic tumor that was first described by Pindborg in 1955. It accounts for less than 1% of all odontogenic neoplasms. The tumor is characterized histologically by the presence of polygonal epithelial cells, calcification, and eosinophilic deposits resembling amyloid. Noncalcifying Pindborg tumor is very rare and only three cases have been documented in the English language literature so far. We present an additional case of noncalcifying Pindborg tumor and review the previously reported cases. Because noncalcifying Pindborg tumor is believed to be an aggressive variant, a definitive resection of the tumor with tumor-free surgical margins and long-term follow-up is recommended.

  13. Compensatory angiogenesis and tumor refractoriness.

    PubMed

    Gacche, R N

    2015-01-01

    Since the establishment of tumor angiogenesis as a therapeutic target, an excitement in developing the anti-angiogenic agents was resulted in tailoring a humanized monoclonal antibody (Bevacizumab) against vascular endothelial growth factor (VEGF): a key factor in recruiting angiogenesis. The past three decades' research in the area of angiogenesis also invented a series of novel and effective anti-angiogenic agents targeting the VEGF signaling axis. Despite the demonstrable clinical benefits of anti-angiogenic therapy, the preclinical and clinical data of the current therapeutic settings clearly indicate the transient efficacy, restoration of tumor progression and aggressive recurrence of tumor invasion after the withdrawal of anti-angiogenic therapy. Therefore, the impact of this therapeutic regime on improving overall survival of patients has been disappointing in clinic. The recent advances in pathophysiology of tumor angiogenesis and related molecular and cellular underpinnings attributed the conspiracy of compensatory angiogenic pathways in conferring evasive and intrinsic tumor resistance to anti-angiogenic agents. The understandings of how these pathways functionally cross-talk for sustaining tumor angiogenesis during VEGF blockade is essential and perhaps may act as a basic prerequisite for designing novel therapeutic strategies to combat the growing arrogance of tumors toward anti-angiogenic agents. The present review offers a discourse on major compensatory angiogenic pathways operating at cellular and molecular levels and their attributes with resistance to anti-angiogenic agents along with strategic opinions on future setting in targeting tumor angiogenesis. PMID:26029827

  14. Study of aggressiveness prediction of mammary adenocarcinoma by Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Andrade Bitar, Renata; da Silva Martinho, Herculano; Zambelli Ramalho, Leandra Náira; dos Santos Junior, Arnaldo Rodrigues; Silva Ramalho, Fernando; Raniero, Leandro; Martin, Airton A.

    2012-01-01

    Although there are many articles focused on in vivo or ex vivo Raman analysis for cancer diagnosis, to the best of our knowledge its potential to predict the aggressiveness of tumor has not been fully explored yet. In this work Raman spectra in the finger print region of ex vivo breast tissues of both healthy mice (normal) and mice with induced mammary gland tumors (abnormal) were measured and associated to matrix metalloproteinase-19 (MMP-19) immunohistochemical exam. It was possible to verify that normal breast, benign lesions, and adenocarcinomas spectra, including the subtypes (cribriform, papillary and solid) could have their aggressiveness diagnosed by vibrational Raman bands. By using MMP- 19 exam it was possible to classify the samples by malignant graduation in accordance to the classification results of Principal Component Analysis (PCA). The spectra NM /MH were classified correctly in 100% of cases; CA/CPA group had 60 % of spectra correctly classified and for PA/AS 54% of the spectra were correctly classified.

  15. A longitudinal study of the association between violent video game play and aggression among adolescents.

    PubMed

    Willoughby, Teena; Adachi, Paul J C; Good, Marie

    2012-07-01

    In the past 2 decades, correlational and experimental studies have found a positive association between violent video game play and aggression. There is less evidence, however, to support a long-term relation between these behaviors. This study examined sustained violent video game play and adolescent aggressive behavior across the high school years and directly assessed the socialization (violent video game play predicts aggression over time) versus selection hypotheses (aggression predicts violent video game play over time). Adolescents (N = 1,492, 50.8% female) were surveyed annually from Grade 9 to Grade 12 about their video game play and aggressive behaviors. Nonviolent video game play, frequency of overall video game play, and a comprehensive set of potential 3rd variables were included as covariates in each analysis. Sustained violent video game play was significantly related to steeper increases in adolescents' trajectory of aggressive behavior over time. Moreover, greater violent video game play predicted higher levels of aggression over time, after controlling for previous levels of aggression, supporting the socialization hypothesis. In contrast, no support was found for the selection hypothesis. Nonviolent video game play also did not predict higher levels of aggressive behavior over time. Our findings, and the fact that many adolescents play video games for several hours every day, underscore the need for a greater understanding of the long-term relation between violent video games and aggression, as well as the specific game characteristics (e.g., violent content, competition, pace of action) that may be responsible for this association. PMID:22040315

  16. Tumor cell metabolism

    PubMed Central

    Romero-Garcia, Susana; Lopez-Gonzalez, Jose Sullivan; B´ez-Viveros, José Luis; Aguilar-Cazares, Dolores

    2011-01-01

    Cancer is a genetic disease that is caused by mutations in oncogenes, tumor suppressor genes and stability genes. The fact that the metabolism of tumor cells is altered has been known for many years. However, the mechanisms and consequences of metabolic reprogramming have just begun to be understood. In this review, an integral view of tumor cell metabolism is presented, showing how metabolic pathways are reprogrammed to satisfy tumor cell proliferation and survival requirements. In tumor cells, glycolysis is strongly enhanced to fulfill the high ATP demands of these cells; glucose carbons are the main building blocks in fatty acid and nucleotide biosynthesis. Glutaminolysis is also increased to satisfy NADPH regeneration, whereas glutamine carbons replenish the Krebs cycle, which produces metabolites that are constantly used for macromolecular biosynthesis. A characteristic feature of the tumor microenvironment is acidosis, which results from the local increase in lactic acid production by tumor cells. This phenomenon is attributed to the carbons from glutamine and glucose, which are also used for lactic acid production. Lactic acidosis also directs the metabolic reprogramming of tumor cells and serves as an additional selective pressure. Finally, we also discuss the role of mitochondria in supporting tumor cell metabolism. PMID:22057267

  17. Sternal Resection and Reconstruction for Malignant Phylloides Tumor.

    PubMed

    Selvakumar, Veda Padma Priya; Poonia, Dharmaram; Agrawal, Juhi; Goel, Ashish; Mehta, Sandeep; Kumar, Kapil

    2015-08-01

    Malignant phylloides tumor is a locally aggressive breast neoplasm constituting less than 1 % of all breast cancers. It has a tendency for local recurrence and management is multidisciplinary. We hereby report a case of total sternal resection and reconstruction using Biopore HDPE prosthesis for Malignant Phylloides tumor. PMID:26702245

  18. Metastasizing mixed tumor of the parotid gland: a rare tumor with unusually rapid progression in a cardiac transplant recipient.

    PubMed

    Sampson, B A; Jarcho, J A; Winters, G L

    1998-11-01

    We report the case of a 69-year-old man who had a mixed tumor (pleomorphic adenoma) removed from his parotid gland 3 years after orthotopic heart transplantation. Two years later, he presented with widely metastatic mixed tumor, which resulted in his death within 6 months. Metastatic mixed tumor is histologically identical to a benign mixed tumor, but it inexplicably metastasizes. Such tumors are rare and have not been reported to date in a transplant recipient. This case illustrates the rapid and aggressive course that malignancies can follow in an immunosuppressed population. Mixed tumors are common salivary neoplasms, so transplant recipients should be carefully followed after resection for evidence of metastatic spread.

  19. Failure-to-Thrive Syndrome Associated with Tumor Formation by Madin–Darby Canine Kidney Cells in Newborn Nude Mice

    PubMed Central

    Brinster, Lauren R; Omeir, Romelda L; Foseh, Gideon S; Macauley, Juliete N; Snoy, Philip J; Beren, Joel J; Teferedegne, Belete; Peden, Keith; Lewis, Andrew M

    2013-01-01

    Tumors that formed in newborn nude mice that were inoculated with 107 Madin–Darby canine kidney (MDCK) cells were associated with a failure-to-thrive (FTT) syndrome consisting of growth retardation, lethargy, weakness, and dehydration. Scoliosis developed in 41% of affected pups. Pups were symptomatic by week 2; severely affected pups became moribund and required euthanasia within 3 to 4 wk. Mice with FTT were classified into categories of mild, moderate, and severe disease by comparing their weight with that of age-matched normal nude mice. The MDCK-induced tumors were adenocarcinomas that invaded adjacent muscle, connective tissue, and bone; 6 of the 26 pups examined had lung metastases. The induction of FTT did not correlate with cell-line aggressiveness as estimated by histopathology or the efficiency of tumor formation (tumor-forming dose 50% endpoint range = 102.8 to 107.5); however, tumor invasion of the paravertebral muscles likely contributed to the scoliosis noted. In contrast to the effect of MDCK cells, tumor formation observed in newborn mice inoculated with highly tumorigenic, human-tumor–derived cell lines was not associated with FTT development. We suggest that tumor formation and FTT are characteristics of these MDCK cell inocula and that FTT represents a new syndrome that may be similar to the cachexia that develops in humans with cancer or other diseases. PMID:24209967

  20. B7-H1 Expression in Wilms Tumor: Correlation With Tumor Biology and Disease Recurrence

    PubMed Central

    Routh, Jonathan C.; Ashley, Richard A.; Sebo, Thomas J.; Lohse, Christine M.; Husmann, Douglas A.; Kramer, Stephen A.; Kwon, Eugene D.

    2009-01-01

    Purpose Despite tremendous gains in improving prognosis, 10% of patients with Wilms tumor will ultimately experience disease recurrence. The identification of novel prognostic markers and tumor associated targets for patients at risk could enable clinicians to treat recurrences more aggressively and, thus, optimize outcomes. We have previously shown that tumor expression of the T cell coregulatory ligand B7-H1 portends a poor prognosis for adults with renal cell carcinoma and represents a promising target to improve therapy. We hypothesize that this finding may be true for Wilms tumor. Materials and Methods We identified 81 patients with Wilms tumor treated at 1 institution between 1968 and 2004. Histopathological features, including Wilms tumor B7-H1 expression, were correlated with clinical observations and outcome. Results Tumor recurrences were noted in 22% of patients with Wilms tumor and 14% died. B7-H1 was expressed in 11 tumors (14%) and was more likely to occur in anaplastic Wilms tumor (p = 0.03). Tumor B7-H1 expression was associated with a 2.7-fold increased risk of recurrence, although this difference did not achieve statistical significance (p = 0.06). However, in favorable histology tumors B7-H1 expression was associated with a 3.7-fold increased risk of recurrence (p = 0.03). Conclusions B7-H1 is expressed by Wilms tumor, correlates with tumor biology and is associated with an increased risk of recurrence in patients with favorable histology tumors. B7-H1 may prove useful in identifying high risk patients who could benefit from more aggressive initial treatment regimens, and may represent a promising therapeutic target. Multi-institutional studies to elucidate the role of B7-H1 in the treatment of Wilms tumor are warranted. PMID:18355839

  1. Threatened Retaliation as an Inhibitor of Human Aggression: Mediating Effects of the Instrumental Value of Aggression.

    ERIC Educational Resources Information Center

    Baron, Robert A.

    Whereas threatened punishment proves effective under conditions where the instrumental value of aggressive behavior is quite low, the following techniques of control may work better in situations where the value of aggression is relatively high: (1) the use of restrained, non-aggressive models; (2) empathic arousal among aggressors; or (3)…

  2. Predicting Aggressive Behavior in Children with the Help of Measures of Implicit and Explicit Aggression

    ERIC Educational Resources Information Center

    Grumm, Mandy; Hein, Sascha; Fingerle, Michael

    2011-01-01

    Aggressive behavior between children in schools is a topic that receives much interest as violence and aggressive behavior cause many maladaptive social outcomes in the school setting. In the current study the Implicit Association Test (IAT) was adapted as a measure of children's implicit aggression, by assessing the association of the self…

  3. Stability of Aggression during Early Adolescence as Moderated by Reciprocated Friendship Status and Friend's Aggression

    ERIC Educational Resources Information Center

    Adams, Ryan E.; Bukowski, William M.; Bagwell, Catherine

    2005-01-01

    The effect of friendship reciprocation and friend aggression on the stability of aggression across a 6-month period following the transition to secondary school was studied in a sample of 298 Grade 6 children from a predominately white, middle-class, Midwestern American community. The stability of aggression was generally high but it varied as a…

  4. Daily associations among anger experience and intimate partner aggression within aggressive and nonaggressive community couples.

    PubMed

    Crane, Cory A; Testa, Maria

    2014-10-01

    Anger is an empirically established precipitant to aggressive responding toward intimate partners. The current investigation examined the effects of anger, as experienced by both partners, as well as gender and previous aggression, on in vivo intimate-partner aggression (IPA) using a prospective daily diary methodology. Participants (N = 118 couples) individually provided 56 consecutive, daily reports of affective experience and partner aggression. Multilevel models were estimated using the actor-partner interdependence model (APIM) framework to analyze the daily associations between anger and partner-aggression perpetration among participating men and women, as moderated by aggression history. Results revealed that both actor and partner anger were generally associated with subsequently reported daily conflict. Further, increases in daily partner anger were associated with corresponding increases in partner aggression among both women who reported high levels of anger and men, regardless of their own anger experience. Increases in actor anger were associated with increases in daily partner aggression only among previously aggressive women. Previously aggressive men and women consistently reported greater perpetration than their nonaggressive counterparts on days of high levels of actors' anger experiences. Results emphasize the importance of both actor and partner factors in partner aggression and suggest that female anger may be a stronger predictor of both female-to-male and male-to-female partner aggression than male anger, when measured at the daily level.

  5. Physiological Arousal, Exposure to a Relatively Lengthy Aggressive Film, and Aggressive Behavior.

    ERIC Educational Resources Information Center

    Thomas, Margaret Hanratty

    1982-01-01

    Studied male students who viewed an aggressive television program or a neutral one. Half of the students were then angered by a confederate. Results indicated angered men who had seen the aggressive film were most aggressive and exhibited the lowest average pulse rates both before and after shock delivery. (Author/JAC)

  6. Relational and Overt Aggression in Urban India: Associations with Peer Relations and Best Friends' Aggression

    ERIC Educational Resources Information Center

    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…

  7. The Relationship of Aggression and Bullying to Social Preference: Differences in Gender and Types of Aggression

    ERIC Educational Resources Information Center

    Lee, Eunju

    2009-01-01

    With 338 fifth-grade students as subjects, this study found the variations in the relation between school bullying and social preference as a function of gender and types of aggressive behavior utilized. Aggressive boys were likely to be rejected by peers, whereas aggressive girls were both rejected and accepted by peers. Children nominated…

  8. Competitive Aggression without Interaction: Effects of Competitive versus Cooperative Instructions on Aggressive Behavior in Video Games.

    ERIC Educational Resources Information Center

    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…

  9. Neurotransmitters regulating feline aggressive behavior.

    PubMed

    Siegel, A; Schubert, K

    1995-01-01

    The experiments described in this review reveal that the expression and modulation of aggressive responses in the cat are organized by two distinct sets of pathways. One set of pathways is associated with the elicitation of a specific form of attack behavior. It includes the medial hypothalamus and its projections to the PAG for the expression of defensive rage behavior and the lateral hypothalamus and its descending projections for the expression of predatory attack behavior. The primary focus of the present review is upon the analysis of defensive rage behavior. It was demonstrated that the pathway from the medial hypothalamus to the PAG, which appears to be essential for elicitation of defensive rage, is powerfully excitatory and utilizes excitatory amino acids that act upon NMDA receptors within the PAG. The other pathways examined in this review arise from different nuclei of the amygdala and are modulatory in nature. Here, two facilitatory systems have been identified. The first involves a projection system from the basal complex of amygdala that projects directly to the PAG. Its excitatory effects are manifest through excitatory amino acids that act upon NMDA receptors within the PAG. The second facilitatory pathway arises from the medial nucleus of the amygdala. However, its projection system is directed to the medial hypothalamus rather than the PAG. Its neurotransmitter appears to be substance P that acts upon NK1 receptors within the medial hypothalamus (see Figure 10). It has yet to be determined whether substance P acts upon any of the other neurokinin receptor subtypes. It should also be pointed out that the substance P pathway from the medial amygdala to the medial hypothalamus functions to suppress predatory attack behavior elicited from the lateral hypothalamus. In this network, it is likely that the modulatory effects of the medial amygdala require the presence of a second, inhibitory pathway from the medial hypothalamus that innervates the

  10. Genetics of aggressive behavior: An overview.

    PubMed

    Veroude, Kim; Zhang-James, Yanli; Fernàndez-Castillo, Noèlia; Bakker, Mireille J; Cormand, Bru; Faraone, Stephen V

    2016-01-01

    The Research Domain Criteria (RDoC) address three types of aggression: frustrative non-reward, defensive aggression and offensive/proactive aggression. This review sought to present the evidence for genetic underpinnings of aggression and to determine to what degree prior studies have examined phenotypes that fit into the RDoC framework. Although the constructs of defensive and offensive aggression have been widely used in the animal genetics literature, the human literature is mostly agnostic with regard to all the RDoC constructs. We know from twin studies that about half the variance in behavior may be explained by genetic risk factors. This is true for both dimensional, trait-like, measures of aggression and categorical definitions of psychopathology. The non-shared environment seems to have a moderate influence with the effects of shared environment being unclear. Human molecular genetic studies of aggression are in an early stage. The most promising candidates are in the dopaminergic and serotonergic systems along with hormonal regulators. Genome-wide association studies have not yet achieved genome-wide significance, but current samples are too small to detect variants having the small effects one would expect for a complex disorder. The strongest molecular evidence for a genetic basis for aggression comes from animal models comparing aggressive and non-aggressive strains or documenting the effects of gene knockouts. Although we have learned much from these prior studies, future studies should improve the measurement of aggression by using a systematic method of measurement such as that proposed by the RDoC initiative. PMID:26345359

  11. Growth and aggressiveness factors affecting Monilinia spp. survival peaches.

    PubMed

    Villarino, M; Melgarejo, P; De Cal, A

    2016-05-01

    Brown rot of stone fruit is caused by three species of Monilinia, Monilinia laxa, M. fructigena, and M. fructicola. Eleven components of 20 different isolates of each of the three Monilinia species were analysed to determine distinct aggressiveness and growth characteristics among the three fungi. M. fructicola showed the greatest lesion diameter, and the lowest incubation and latency period on fruit postharvest, however isolates of M. fructigena exhibited less aggressiveness components. Five growth characteristics of M. fructicola could be used to distinguish M. fructicola from the other two species. The dendrogram generated from only the presence of sclerotia and lesion length on infected fruit separated the 60 isolates into two clusters (r=0.93). One cluster was composed of the M. laxa and M. fructigena isolates and the other cluster comprised the M. fructicola isolates. However, the dendrogram generated based on the presence of stromata and sclerotia in the same colony of the three species when they were grown on potato dextrose agar, and the lesion diameter on fruit infected with each species separated the 60 isolates into three clusters (r=0.81). Each cluster comprised the isolates of each of three Monilinia spp. We discussed the effect of M. fructicola growth and aggressiveness differences on the displacement of M. laxa and M. fructigena by M. fructicola recorded in Spanish peach orchards and their effect on brown rot at postharvest.

  12. Growth and aggressiveness factors affecting Monilinia spp. survival peaches.

    PubMed