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Sample records for aggressive tumour phenotype

  1. Surgery for locally aggressive bone tumours.

    PubMed

    Devitt, A; O'Sullivan, T; Kavanagh, M; Hurson, B J

    1996-01-01

    Treatment of 16 patients with aggressive benign bone tumours and one patient with a low grade malignancy with a combined regimen of cryosurgery, phenolization and acrylic cementation is reported. Patients were aged between 9 and 51 years and were treated by this method between the years 1986 and 1993. Minimal follow up was 13 months. The commonest histological diagnosis was giant cell tumour (7), followed by aneurysmal bone cyst (6), chondromyxoidfibroma (3) and low grade chondrosarcoma (1). Patients were assessed for functional outcome and local recurrence. On average 86 per cent of premorbid function was restored at follow up and there was one local recurrence (6.29 per cent). We conclude that this is a satisfactory method of gaining local control of these tumours. PMID:8990655

  2. Uncommon perineal tumours: caution with aggressive surgical management

    PubMed Central

    Duchalais, Emilie; Cassagnau, Elisabeth; Regenet, Nicolas; Meurette, Guillaume

    2013-01-01

    An asymptomatic 66-year-old woman showed a large perineal mass extending close to pelvic organs on MRI. CT-guided needle biopsies revealed a desmoid tumour (DT). The patient refused radical surgery. Four years later, the tumour had marginally increased in size and was still asymptomatic. The revision of earlier biopsies then revealed typical aspects of aggressive angiomyxoma (AA). AA and DT are rare mesenchymal tumours of low-grade malignancy, usually of large size, that occurs in female pelvi-perineal region. Radical resection with wide margins is classically advocated in such tumours in order to prevent the high risk of recurrences. However, due to a slow growth, rare infiltration of adjacent organs and a very low metastatic potential, a watchful waiting policy can be proposed when high postoperative morbidity is expected. In order to propose the accurate treatment, frontline biopsies of the tumour are essential. PMID:24243505

  3. Delay in treatment of primary malignant and aggressive musculoskeletal tumours.

    PubMed

    Pan, K L; Zolqarnain, A; Chia, Y Y

    2006-02-01

    Patients with aggressive musculoskeletal tumours often arrive at specialised treatment centres late. Such a delay could mean disfavour for potentially curable or long-term disease-free outcome of limb preserving surgery. This study was undertaken to identify the underlying problem-related delay with a view to propose solution for solving it. We reviewed 30 patients to determine the periods of delay between onset of the first symptom and the definitive treatment. The delays were categorized as 'patient' delay, 'referral' delay and 'treatment' delay. There was 'patient' delay in 57% of patients (n=17), ranging from 1 to 18 months; 'referral' delay in 67% of patients (n=20) ranging from 1 to 19 months and 23% of patients (n=7) had treatment delay (average 23 days) at the treatment centre. The causes of late arrival are not solely patient-related but are multifactorial. Measures to minimize such delays include enhancing awareness only with high index of suspicion among primary care practitioners, creating a special lane specialized imaging studies and establishing a dedicated musculoskeletal tumour unit. PMID:17042231

  4. Management of locally aggressive mandibular tumours using a gas combination cryosurgery.

    PubMed

    Carneiro, José Thiers; Falcão, Aline Semblano Carreira; da Silva Tabosa, Ana Karla; Shinohara, Elio Hitoshi; de Menezes, Lucas Machado

    2014-07-01

    This study evaluated the results of curettage followed by cryosurgery using a combination of propane, butane, and isobutane gas for several benign but locally aggressive bone tumours on the mandible. Twenty-nine patients (16 men and 13 women) participated in the study. Patient ages ranged from 6 to 87 years (mean, 23.72 years). Before enucleation and cryosurgery, some patients received prior treatment consisting of marsupialisation to decrease tumour size. Twenty-seven of the 29 patients (93.10%) showed no evidence of clinical or radiographic recurrence after treatment through enucleation and cryosurgery. Wound dehiscence, which was observed in all cases, healed by second intention. The average follow-up period was 70.55 months (range, 53-120 months). These results suggest that enucleation followed by cryosurgery is an effective therapy for managing locally aggressive mandible tumours. In addition, this treatment is a less expensive intervention than more radical procedures. PMID:23835572

  5. Surgical treatment of extra-abdominal desmoid tumours (aggressive fibromatoses).

    PubMed

    Higaki, S; Tateishi, A; Ohno, T; Abe, S; Ogawa, K; Iijima, T; Kojima, T

    1995-01-01

    Extra-abdominal desmoid tumours (EADT) are benign lesions but difficult to cure because of their infiltrative nature and tendency to recur. Among many treatments recommended in the past, wide excision has been successful, even in difficult cases. We have analyzed retrospectively 41 cases of histologically confirmed EADTs. A total of 98 operations were performed on these patients: 29 wide excisions on 22 patients, 52 intra-lesional excisions with wide margins on 16 patients, and 17 incomplete excisions on 3 patients. One patient, with intra-pelvic lesions, died of a massive haemorrhage 3 days after surgery. Forty patients were followed from between 3 and 29 years. One, who had a multicentric EADT for 21 years, died from the disease. The significant factors concerning local recurrence after wide procedures were an unsatisfactory initial wide local excision, disease affecting 4 or more muscles and the invasive nature of the recurrences. We recommend wide local excision of these tumours in all anatomical areas that allow this procedure. When major nerves and vessels are involved, we recommend an intralesional excision with wide margins in order to preserve limb function. Radiation therapy should be confined to cases in which wide local procedures are not feasible. Overall, 37 of our patients (90%) were cured of the disease, 2 had their disease controlled, and 2 died.

  6. p53 suppresses type II endometrial carcinomas in mice and governs endometrial tumour aggressiveness in humans

    PubMed Central

    Wild, Peter J; Ikenberg, Kristian; Fuchs, Thomas J; Rechsteiner, Markus; Georgiev, Strahil; Fankhauser, Niklaus; Noske, Aurelia; Roessle, Matthias; Caduff, Rosmarie; Dellas, Athanassios; Fink, Daniel; Moch, Holger; Krek, Wilhelm; Frew, Ian J

    2012-01-01

    Type II endometrial carcinomas are a highly aggressive group of tumour subtypes that are frequently associated with inactivation of the TP53 tumour suppressor gene. We show that mice with endometrium-specific deletion of Trp53 initially exhibited histological changes that are identical to known precursor lesions of type II endometrial carcinomas in humans and later developed carcinomas representing all type II subtypes. The mTORC1 signalling pathway was frequently activated in these precursor lesions and tumours, suggesting a genetic cooperation between this pathway and Trp53 deficiency in tumour initiation. Consistent with this idea, analyses of 521 human endometrial carcinomas identified frequent mTORC1 pathway activation in type I as well as type II endometrial carcinoma subtypes. mTORC1 pathway activation and p53 expression or mutation status each independently predicted poor patient survival. We suggest that molecular alterations in p53 and the mTORC1 pathway play different roles in the initiation of the different endometrial cancer subtypes, but that combined p53 inactivation and mTORC1 pathway activation are unifying pathogenic features among histologically diverse subtypes of late stage aggressive endometrial tumours. PMID:22678923

  7. 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

  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. PMID:24787296

  9. 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.

  10. Multi-Detector Computed Tomography in Evaluating Locally Aggressive and Malignant Bone Tumours

    PubMed Central

    Ramavathu, Kumar Venu Madhav; Garga, U.C.

    2015-01-01

    Objective: To evaluate the ability of Multi-Detector Computed Tomography in preoperative evaluation of locally aggressive and malignant bone tumours in correlation with histopathological findings. Materials and Methods: Twenty patients suspected of malignant bone tumours on the basis of their clinical profile were selected. Following a plain radiograph evaluation, all of them were subjected to CT scan examination. Multi Planar Reconstruction (MPR) was done in sagittal and coronal planes and also three-dimensional Volume Rendering (VR) and Maximum Intensity Projection (MIP) images were obtained. Results: Of the 20 patients, 18 underwent surgery, and their histopathological findings were compared and correlated with MDCT findings. MDCT was 92.8% sensitive and 100% specific in determining the vascularity of the tumour and also can detect displacement/ encasement/ involvement of adjacent vessels. It has a sensitivity and specificity of 100% in determining cortical break, calcification and periosteal reaction. However, it is less sensitive in detecting joint involvement. Post contrast enhancement gives details of the extent of the soft tissue component. Conclusion: Although MRI is a preferred modality in preoperative evaluation of bone tumours, CT may be used an alternative in case of non-availability of MRI, which has faster acquisition time and better resolution. Using three dimensional MPR imaging, the location and extent of the tumour can be studied. It is also useful in determining cortical discontinuity, periosteal reaction, and calcification. By virtue of MIP and VR imaging, vascularity of the tumour and its relationship with the adjacent vasculature can be established. However, it is inferior to MRI in soft tissue characterization and has poor sensitivity in detecting marrow and joint involvement. PMID:26023618

  11. Aggressive osseous commitment result by keratocyst odontogenic tumour: case report, radiographic and clinical standpoints

    PubMed Central

    Cardoso, Gerusa O.M.; Matta-Neto, Edgard; El Achkar, Vivian N. R.; Niccoli-Filho, Walter

    2013-01-01

    Keratocystic odontogenic tumour (KCOT) previously known as odontogenic keratocyst was recently classified as a benign lesion characterized by an infiltrating pattern, local aggressiveness with the propensity to recurrence. It is thought to arise from the dental lamina. Pain is usually not associated with KCOT until swelling occurs, and it commonly affects the posterior mandible. Multiple KCOT are associated with nevoid basal cell carcinoma syndrome. This study reports an aggressive case of KCOT with destruction of the osseous tissue of the mandible, accentuated face asymmetry, dysphagia and dysphonia. It was managed with a defined protocol which entailed diagnosis, treatment with enucleation along with peripheral ostectomy and rehabilitation. A long-term follow-up schedule was provided to the patient to observe the recurrence behaviour of this cyst. In postoperative phase, no complication was noticed regarding wound healing and recurrence. PMID:24964453

  12. Neuroblastoma patient-derived orthotopic xenografts retain metastatic patterns and geno- and phenotypes of patient tumours.

    PubMed

    Braekeveldt, Noémie; Wigerup, Caroline; Gisselsson, David; Mohlin, Sofie; Merselius, My; Beckman, Siv; Jonson, Tord; Börjesson, Anna; Backman, Torbjörn; Tadeo, Irene; Berbegall, Ana P; Ora, Ingrid; Navarro, Samuel; Noguera, Rosa; Påhlman, Sven; Bexell, Daniel

    2015-03-01

    Neuroblastoma is a childhood tumour with heterogeneous characteristics and children with metastatic disease often have a poor outcome. Here we describe the establishment of neuroblastoma patient-derived xenografts (PDXs) by orthotopic implantation of viably cryopreserved or fresh tumour explants of patients with high risk neuroblastoma into immunodeficient mice. In vivo tumour growth was monitored by magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography. Neuroblastoma PDXs retained the undifferentiated histology and proliferative capacity of their corresponding patient tumours. The PDXs expressed neuroblastoma markers neural cell adhesion molecule, chromogranin A, synaptophysin and tyrosine hydroxylase. Whole genome genotyping array analyses demonstrated that PDXs retained patient-specific chromosomal aberrations such as MYCN amplification, deletion of 1p and gain of chromosome 17q. Thus, neuroblastoma PDXs recapitulate the hallmarks of high-risk neuroblastoma in patients. PDX-derived cells were cultured in serum-free medium where they formed free-floating neurospheres, expressed neuroblastoma gene markers MYCN, CHGA, TH, SYP and NPY, and retained tumour-initiating and metastatic capacity in vivo. PDXs showed much higher degree of infiltrative growth and distant metastasis as compared to neuroblastoma SK-N-BE(2)c cell line-derived orthotopic tumours. Importantly, the PDXs presented with bone marrow involvement, a clinical feature of aggressive neuroblastoma. Thus, neuroblastoma PDXs serve as clinically relevant models for studying and targeting high-risk metastatic neuroblastoma.

  13. Igf2 ligand dependency of Pten(+/-) developmental and tumour phenotypes in the mouse.

    PubMed

    Church, D N; Phillips, B R; Stuckey, D J; Barnes, D J; Buffa, F M; Manek, S; Clarke, K; Harris, A L; Carter, E J; Hassan, A B

    2012-08-01

    The tumour suppressor PTEN is a key negative regulator of the PI3K-Akt pathway, and is frequently either reduced or lost in human tumours. Murine genetic studies have confirmed that reduction of Pten promotes tumourigenesis in multiple organs, and demonstrated dependency of tumour development on the activation of downstream components such as Akt. Insulin-like growth factors (IGFs) act via IGF1R to activate the PI3K-Akt pathway, and are commonly upregulated in cancer. A context-dependent interplay between IGFs and PTEN exists in normal tissue and tumours; increased IGF2 ligand supply induces Pten expression creating an autoregulatory negative feedback loop, whereas complete loss of PTEN may either cooperate with IGF overexpression in tumour promotion, or result in desensitisation to IGF ligand. However, it remains unknown whether neoplasia associated with Pten loss is dependent on upstream IGF ligand supply in vivo. We evaluated this by generation of Pten(+/-) mice with differing allelic dosage of Igf2, an imprinted gene encoding the potent embryonic and tumour growth factor Igf2. We show that biallelic Igf2 supply potentiates a previously unreported Pten(+/-) placental phenotype and results in strain-dependent cardiac hyperplasia and neonatal lethality. Importantly, we also show that the effects of Pten loss in vivo are modified by Igf2 supply, as lack of Igf2 results in extended survival and delayed tumour development while biallelic supply is associated with reduced lifespan and accelerated neoplasia in females. Furthermore, we demonstrate that reduction of PTEN protein to heterozygote levels in human MCF7 cells is associated with increased proliferation in response to IGF2, and does not result in desensitisation to IGF2 signalling. These data indicate that the effects of Pten loss at heterozygote levels commonly observed in human tumours are modified by Igf2 ligand, and emphasise the importance of the evaluation of upstream pathways in tumours with Pten loss

  14. Vocalizations convey sex, seasonal phenotype, and aggression in a seasonal mammal.

    PubMed

    Rendon, Nikki M; Keesom, Sarah M; Amadi, Chima; Hurley, Laura M; Demas, Gregory E

    2015-12-01

    Seasonal variation in social behavior is often accompanied by seasonal variation in communication. In mammals, how seasonal environmental cues influence aggressive vocalizations remains underexplored. Photoperiod is the primary cue coordinating seasonal responses in most temperate zone animals, including Siberian hamsters (Phodopus sungorus), a species that undergoes reproductive inhibition and increased aggression in winter. During same-sex aggressive encounters, hamsters emit both broadband calls (BBCs) and ultrasonic vocalizations (USVs) that indicate aggression and the vocalizer's sex, respectively; however, it is not known whether these rodents adjust specific elements of their vocal repertoire to reflect their photoperiod-induced seasonal phenotypes. To address this, we recorded vocalizations emitted during dyadic interactions between male or female pairs of hamsters housed in long or short photoperiods and measured serum testosterone levels. USV emission rate remained stable across photoperiods, but proportional use of USV subtypes varied in novel ways: 'jump' USVs were sensitive to seasonal phenotype, but not the vocalizer's sex, whereas 'plain' USVs were sensitive only to the sex of the vocalizer. BBC emission rate varied with seasonal phenotype; short-day non-reproductive hamsters produced more BBCs and demonstrated increased aggression compared with reproductive hamsters. Testosterone, however, was not related to vocalization rates. Collectively, these findings demonstrate that changes in the vocal repertoire of Siberian hamsters reflect sex, aggression, and seasonal phenotype, suggesting that both BBCs and USVs are important signals used during same-sex social encounters. PMID:26386405

  15. Vocalizations convey sex, seasonal phenotype, and aggression in a seasonal mammal.

    PubMed

    Rendon, Nikki M; Keesom, Sarah M; Amadi, Chima; Hurley, Laura M; Demas, Gregory E

    2015-12-01

    Seasonal variation in social behavior is often accompanied by seasonal variation in communication. In mammals, how seasonal environmental cues influence aggressive vocalizations remains underexplored. Photoperiod is the primary cue coordinating seasonal responses in most temperate zone animals, including Siberian hamsters (Phodopus sungorus), a species that undergoes reproductive inhibition and increased aggression in winter. During same-sex aggressive encounters, hamsters emit both broadband calls (BBCs) and ultrasonic vocalizations (USVs) that indicate aggression and the vocalizer's sex, respectively; however, it is not known whether these rodents adjust specific elements of their vocal repertoire to reflect their photoperiod-induced seasonal phenotypes. To address this, we recorded vocalizations emitted during dyadic interactions between male or female pairs of hamsters housed in long or short photoperiods and measured serum testosterone levels. USV emission rate remained stable across photoperiods, but proportional use of USV subtypes varied in novel ways: 'jump' USVs were sensitive to seasonal phenotype, but not the vocalizer's sex, whereas 'plain' USVs were sensitive only to the sex of the vocalizer. BBC emission rate varied with seasonal phenotype; short-day non-reproductive hamsters produced more BBCs and demonstrated increased aggression compared with reproductive hamsters. Testosterone, however, was not related to vocalization rates. Collectively, these findings demonstrate that changes in the vocal repertoire of Siberian hamsters reflect sex, aggression, and seasonal phenotype, suggesting that both BBCs and USVs are important signals used during same-sex social encounters.

  16. Lack of MHC class I antigens and tumour aggressiveness of the squamous cell carcinoma of the larynx.

    PubMed Central

    Esteban, F.; Concha, A.; Delgado, M.; Pérez-Ayala, M.; Ruiz-Cabello, F.; Garrido, F.

    1990-01-01

    A series of 60 primary laryngeal and hypopharyngeal tumours, 24 lymph node metastases and normal tissue were evaluated in frozen sections for the expression of MHC class I antigens, using monoclonal antibodies and the APAAP technique. We found 13 tumours presenting total HLA-ABC loss, five with selective loss of HLA-A antigens and one with absence of HLA-B antigens. These losses were statistically associated with clinical and pathological parameters, such as T stage, degree of differentiation, scores according to the Jakobsson and Glanz grading systems and degree of leukocytic infiltration. Our results lead us to the following conclusions: (a) HLA class I losses were found in a group of tumours showing greater aggressiveness and worse prognosis; (b) these alterations in expression were not associated with an increased metastatic potential. Thus, the absence of HLA molecules in laryngeal tumours is related to greater local aggressiveness, and the loss of class I antigens seems to constitute an adaptive tumour mechanism to avoid the different anatomical and immunological barriers within the larynx. Images Figure 1 Figure 2 PMID:2257212

  17. Altering an extended phenotype reduces intraspecific male aggression and can maintain diversity in cichlid fish

    PubMed Central

    Croft, Guy E.; Joyce, Domino A.

    2013-01-01

    Reduced male aggression towards different phenotypes generating negative frequency-dependent intrasexual selection has been suggested as a mechanism to facilitate the invasion and maintenance of novel phenotypes in a population. To date, the best empirical evidence for the phenomenon has been provided by laboratory studies on cichlid fish with different colour polymorphisms. Here we experimentally tested the hypothesis in a natural population of Lake Malawi cichlid fish, in which males build sand-castles (bowers) to attract females during seasonal leks. We predicted that if bower shape plays an important role in male aggressive interactions, aggression among conspecific males should decrease when their bower shape is altered. Accordingly, we allocated randomly chosen bowers in a Nyassachromis cf. microcephalus lek into three treatments: control, manipulated to a different shape, and simulated manipulation. We then measured male behaviours and bower shape before and after these treatments. We found that once bower shape was altered, males were involved in significantly fewer aggressive interactions with conspecific males than before manipulation. Mating success was not affected. Our results support the idea that an extended phenotype, such as bower shape, can be important in maintaining polymorphic populations. Specifically, reduced male conspecific aggression towards males with different extended phenotypes (here, bower shapes) may cause negative frequency-dependent selection, allowing the invasion and establishment of a new phenotype (bower builder). This could help our understanding of mechanisms of diversification within populations, and in particular, the overall diversification of bower shapes within Lake Malawi cichlids. PMID:24349896

  18. Functional characterisation of osteosarcoma cell lines and identification of mRNAs and miRNAs associated with aggressive cancer phenotypes

    PubMed Central

    Lauvrak, S U; Munthe, E; Kresse, S H; Stratford, E W; Namløs, H M; Meza-Zepeda, L A; Myklebost, O

    2013-01-01

    Background: Osteosarcoma is the most common primary malignant bone tumour, predominantly affecting children and adolescents. Cancer cell line models are required to understand the underlying mechanisms of tumour progression and for preclinical investigations. Methods: To identify cell lines that are well suited for studies of critical cancer-related phenotypes, such as tumour initiation, growth and metastasis, we have evaluated 22 osteosarcoma cell lines for in vivo tumorigenicity, in vitro colony-forming ability, invasive/migratory potential and proliferation capacity. Importantly, we have also identified mRNA and microRNA (miRNA) gene expression patterns associated with these phenotypes by expression profiling. Results: The cell lines exhibited a wide range of cancer-related phenotypes, from rather indolent to very aggressive. Several mRNAs were differentially expressed in highly aggressive osteosarcoma cell lines compared with non-aggressive cell lines, including RUNX2, several S100 genes, collagen genes and genes encoding proteins involved in growth factor binding, cell adhesion and extracellular matrix remodelling. Most notably, four genes—COL1A2, KYNU, ACTG2 and NPPB—were differentially expressed in high and non-aggressive cell lines for all the cancer-related phenotypes investigated, suggesting that they might have important roles in the process of osteosarcoma tumorigenesis. At the miRNA level, miR-199b-5p and mir-100-3p were downregulated in the highly aggressive cell lines, whereas miR-155-5p, miR-135b-5p and miR-146a-5p were upregulated. miR-135b-5p and miR-146a-5p were further predicted to be linked to the metastatic capacity of the disease. Interpretation: The detailed characterisation of cell line phenotypes will support the selection of models to use for specific preclinical investigations. The differentially expressed mRNAs and miRNAs identified in this study may represent good candidates for future therapeutic targets. To our knowledge, this is

  19. Confirmation of FWT1 as a Wilms' tumour susceptibility gene and phenotypic characteristics of Wilms' tumour attributable to FWT1.

    PubMed

    Rahman, N; Abidi, F; Ford, D; Arbour, L; Rapley, E; Tonin, P; Barton, D; Batcup, G; Berry, J; Cotter, F; Davison, V; Gerrard, M; Gray, E; Grundy, R; Hanafy, M; King, D; Lewis, I; Ridolfi Luethy, A; Madlensky, L; Mann, J; O'Meara, A; Oakhill, T; Skolnick, M; Strong, L; Stratton, M R

    1998-11-01

    A susceptibility gene for Wilms' tumour (WT), designated FWT1, was previously mapped to chromosome 17q12-q21 by linkage analysis of a single family. We now confirm the existence of this gene by analysis of additional cases in the original family (3-point LOD score=5.69), and by detecting strong evidence of linkage to this region in an unrelated pedigree with seven cases of WT (3-point LOD score=2.56). Analysis of 11 smaller WT families confirms that there is genetic heterogeneity in familial WT, as three families exhibit strong evidence against linkage to FWT1. One of these was subsequently found to have a predisposing WT1 mutation. However, the other two families show evidence against both FWT1 and WT1, suggesting that at least one further familial WT gene exists. Analysis of the phenotype of 16 WT cases from the families linked to FWT1 demonstrates that they present at a significantly older age and a significantly later stage than both sporadic WT and the six cases from two families unlinked to either FWT1 or WT1. The results confirm the role of FWT1 in susceptibility to WT, provide strong evidence for genetic heterogeneity in familial WT and suggest there are phenotypic differences between familial WT due to FWT1, familial WT due to other genes and non-familial WT. PMID:9860296

  20. Addition of vasopressin synthetic analogue [V(4)Q(5)]dDAVP to standard chemotherapy enhances tumour growth inhibition and impairs metastatic spread in aggressive breast tumour models.

    PubMed

    Garona, Juan; Pifano, Marina; Pastrian, Maria B; Gomez, Daniel E; Ripoll, Giselle V; Alonso, Daniel F

    2016-08-01

    [V(4)Q(5)]dDAVP is a novel 2nd generation vasopressin analogue with robust antitumour activity against metastatic breast cancer. We recently reported that, by acting on vasopressin V2r membrane receptor present in tumour cells and microvascular endothelium, [V(4)Q(5)]dDAVP inhibits angiogenesis and metastatic progression of the disease without overt toxicity. Despite chemotherapy remaining as a primary therapeutic option for aggressive breast cancer, its use is limited by low selectivity and associated adverse effects. In this regard, we evaluated potential combinational benefits by adding [V(4)Q(5)]dDAVP to standard-of-care chemotherapy. In vitro, combination of [V(4)Q(5)]dDAVP with sub-IC50 concentrations of paclitaxel or carmustine resulted in a cooperative inhibition of breast cancer cell growth in comparison to single-agent therapy. In vivo antitumour efficacy of [V(4)Q(5)]dDAVP addition to chemotherapy was first evaluated using the triple-negative MDA-MB-231 breast cancer xenograft model. Tumour-bearing mice were treated with i.v. injections of [V(4)Q(5)]dDAVP (0.3 μg/kg, thrice weekly) in combination with weekly cycles of paclitaxel (10 mg/kg i.p.). After 6 weeks of treatment, combination regimen resulted in greater tumour growth inhibition compared to monotherapy. [V(4)Q(5)]dDAVP addition was also associated with reduction of local aggressiveness, and impairment of tumour invasion and infiltration of the skin. Benefits of combined therapy were confirmed in the hormone-independent and metastatic F3II breast cancer model by combining [V(4)Q(5)]dDAVP with carmustine (25 mg/kg i.p.). Interestingly, [V(4)Q(5)]dDAVP plus cytotoxic agents severely impaired colony forming ability of tumour cells and inhibited breast cancer metastasis to lung. The present study shows that [V(4)Q(5)]dDAVP may complement conventional chemotherapy by modulating metastatic progression and early stages of microtumour establishment, and thus supports further preclinical testing of

  1. Addition of vasopressin synthetic analogue [V(4)Q(5)]dDAVP to standard chemotherapy enhances tumour growth inhibition and impairs metastatic spread in aggressive breast tumour models.

    PubMed

    Garona, Juan; Pifano, Marina; Pastrian, Maria B; Gomez, Daniel E; Ripoll, Giselle V; Alonso, Daniel F

    2016-08-01

    [V(4)Q(5)]dDAVP is a novel 2nd generation vasopressin analogue with robust antitumour activity against metastatic breast cancer. We recently reported that, by acting on vasopressin V2r membrane receptor present in tumour cells and microvascular endothelium, [V(4)Q(5)]dDAVP inhibits angiogenesis and metastatic progression of the disease without overt toxicity. Despite chemotherapy remaining as a primary therapeutic option for aggressive breast cancer, its use is limited by low selectivity and associated adverse effects. In this regard, we evaluated potential combinational benefits by adding [V(4)Q(5)]dDAVP to standard-of-care chemotherapy. In vitro, combination of [V(4)Q(5)]dDAVP with sub-IC50 concentrations of paclitaxel or carmustine resulted in a cooperative inhibition of breast cancer cell growth in comparison to single-agent therapy. In vivo antitumour efficacy of [V(4)Q(5)]dDAVP addition to chemotherapy was first evaluated using the triple-negative MDA-MB-231 breast cancer xenograft model. Tumour-bearing mice were treated with i.v. injections of [V(4)Q(5)]dDAVP (0.3 μg/kg, thrice weekly) in combination with weekly cycles of paclitaxel (10 mg/kg i.p.). After 6 weeks of treatment, combination regimen resulted in greater tumour growth inhibition compared to monotherapy. [V(4)Q(5)]dDAVP addition was also associated with reduction of local aggressiveness, and impairment of tumour invasion and infiltration of the skin. Benefits of combined therapy were confirmed in the hormone-independent and metastatic F3II breast cancer model by combining [V(4)Q(5)]dDAVP with carmustine (25 mg/kg i.p.). Interestingly, [V(4)Q(5)]dDAVP plus cytotoxic agents severely impaired colony forming ability of tumour cells and inhibited breast cancer metastasis to lung. The present study shows that [V(4)Q(5)]dDAVP may complement conventional chemotherapy by modulating metastatic progression and early stages of microtumour establishment, and thus supports further preclinical testing of

  2. Igf2 pathway dependency of the Trp53 developmental and tumour phenotypes

    PubMed Central

    Haley, Victoria L; Barnes, David J; Sandovici, Ionel; Constancia, Miguel; Graham, Christopher F; Pezzella, Francesco; Bühnemann, Claudia; Carter, Emma J; Hassan, A Bassim

    2012-01-01

    Insulin-like growth factor 2 (IGF2) and the transformation related protein 53 (Trp53) are potent regulators of cell growth and metabolism in development and cancer. In vitro evidence suggests several mechanistic pathway interactions. Here, we tested whether loss of function of p53 leads to IGF2 ligand pathway dependency in vivo. Developmental lethality occurred in p53 homozygote null mice that lacked the paternal expressed allele of imprinted Igf2. Further lethality due to post-natal lung haemorrhage occurred in female progeny with Igf2 paternal null allele only if derived from double heterozygote null fathers, and was associated with a specific gene expression signature. Conditional deletion of Igf2fl/fl attenuated the rapid tumour onset promoted by homozygous deletion of p53fl/fl. Accelerated carcinoma and sarcoma tumour formation in p53+/− females with bi-allelic Igf2 expression was associated with reductions in p53 loss of heterozygosity and apoptosis. Igf2 genetic dependency of the p53 null phenotype during development and tumour formation suggests that targeting the IGF2 pathway may be useful in the prevention and treatment of human tumours with a disrupted Trp53 pathway. PMID:22674894

  3. No aggression in a 4-year-old boy with an androgen-producing tumour: Case Report

    PubMed Central

    De la Marche, Wouter; Prinsen, Karin; Boot, Annemieke M; Ferdinand, Robert F

    2005-01-01

    Background The androgen testosterone plays a critical role in many aspects of sexual differentiation. Also, it is thought to induce aggressive behaviours or to play a role in social dominance. Case presentation In this case report a 4-year-old boy is described whose testosterone and dehydroepiandrosterone sulphate (DHEA-S) levels were raised to pubertal levels due to a testosterone producing testis tumour. This provided the unique opportunity to examine the effects of elevated levels of androgens on levels of aggression or on social dominance before the onset of puberty. Conclusion The present case report does not support the hypothesis of a causal relationship between testosterone and aggression or between testosterone and social dominance in young children. PMID:16202122

  4. Decreased FOXJ1 expression and its ciliogenesis programme in aggressive ependymoma and choroid plexus tumours.

    PubMed

    Abedalthagafi, Malak S; Wu, Michael P; Merrill, Parker H; Du, Ziming; Woo, Terri; Sheu, Shu-Hsien; Hurwitz, Shelley; Ligon, Keith L; Santagata, Sandro

    2016-03-01

    Well-differentiated human cancers share transcriptional programmes with the normal tissue counterparts from which they arise. These programmes broadly influence cell behaviour and function and are integral modulators of malignancy. Here, we show that the master regulator of motile ciliogenesis, FOXJ1, is highly expressed in cells along the ventricular surface of the human brain. Strong expression is present in cells of the ependyma and the choroid plexus as well as in a subset of cells residing in the subventricular zone. Expression of FOXJ1 and its transcriptional programme is maintained in many well-differentiated human tumours that arise along the ventricle, including low-grade ependymal tumours and choroid plexus papillomas. Anaplastic ependymomas as well as choroid plexus carcinomas show decreased FOXJ1 expression and its associated ciliogenesis programme genes. In ependymomas and choroid plexus tumours, reduced expression of FOXJ1 and its ciliogenesis programme are markers of poor outcome and are therefore useful biomarkers for assessing these tumours. Transitions in ciliogenesis define distinct differentiation states in ependymal and choroid plexus tumours with important implications for patient care. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:26690880

  5. Urinary volatile compounds differ across reproductive phenotypes and following aggression in male Siberian hamsters.

    PubMed

    Rendon, Nikki M; Soini, Helena A; Scotti, Melissa-Ann L; Novotny, Milos V; Demas, Gregory E

    2016-10-01

    Chemical communication plays an integral role in social behavior by facilitating social encounters, allowing for the evaluation of social partners, defining territories and advertising information such as species and sex. Odors provide information about the social environment for rodents and other mammals; however, studies identifying chemical compounds and their functions have thus far focused primarily on a few species. In addition, considerably less attention has been focused on how environmental factors and behavioral context alter these compounds during periods of reproductive quiescence. We examined the effects of photoperiod and social context on chemical communication in the seasonally breeding Siberian hamster which displays modest territorial aggression during long "summer-like" days, but increased aggression in short "winter-like" days. We collected urine samples from long- and short-day male hamsters to investigate how photoperiod and subsequent changes in reproductive phenotype alter urinary volatile compound profiles. Next, we identified changes in urinary compounds before and after an aggressive encounter. Male hamsters exhibited a diverse urinary profile across photoperiods; however, long-day reproductive males showed higher levels of individual compounds when compared to short-day non-reproductive males. In addition, individual compounds were altered following an aggressive encounter; some changed only in long days whereas others changed regardless of photoperiod. Further, aggression and circulating levels of testosterone were positively correlated with urinary compounds in long-, but not short-day males. These findings suggest both photoperiod- and aggression-specific physiological regulation of urinary compounds in this species and contribute to a greater understanding of chemical communication more broadly.

  6. Urinary volatile compounds differ across reproductive phenotypes and following aggression in male Siberian hamsters.

    PubMed

    Rendon, Nikki M; Soini, Helena A; Scotti, Melissa-Ann L; Novotny, Milos V; Demas, Gregory E

    2016-10-01

    Chemical communication plays an integral role in social behavior by facilitating social encounters, allowing for the evaluation of social partners, defining territories and advertising information such as species and sex. Odors provide information about the social environment for rodents and other mammals; however, studies identifying chemical compounds and their functions have thus far focused primarily on a few species. In addition, considerably less attention has been focused on how environmental factors and behavioral context alter these compounds during periods of reproductive quiescence. We examined the effects of photoperiod and social context on chemical communication in the seasonally breeding Siberian hamster which displays modest territorial aggression during long "summer-like" days, but increased aggression in short "winter-like" days. We collected urine samples from long- and short-day male hamsters to investigate how photoperiod and subsequent changes in reproductive phenotype alter urinary volatile compound profiles. Next, we identified changes in urinary compounds before and after an aggressive encounter. Male hamsters exhibited a diverse urinary profile across photoperiods; however, long-day reproductive males showed higher levels of individual compounds when compared to short-day non-reproductive males. In addition, individual compounds were altered following an aggressive encounter; some changed only in long days whereas others changed regardless of photoperiod. Further, aggression and circulating levels of testosterone were positively correlated with urinary compounds in long-, but not short-day males. These findings suggest both photoperiod- and aggression-specific physiological regulation of urinary compounds in this species and contribute to a greater understanding of chemical communication more broadly. PMID:27212202

  7. Comparative gene expression profiles for highly similar aggressive phenotypes in male and female cichlid fishes (Julidochromis)

    PubMed Central

    Schumer, Molly; Krishnakant, Kavita; Renn, Suzy C. P.

    2011-01-01

    SUMMARY Julidochromis marlieri and Julidochromis transcriptus are two closely related Tanganyikan cichlids that have evolved different behavior and mating strategies since they diverged from their common ancestor. While J. transcriptus follows the ancestral pattern of male dominance, male-biased sexual size dimorphism and territoriality, the pattern is reversed in J. marlieri. In J. marlieri, females show all of these behavioral and morphological characteristics. This raises the question of whether female J. marlieri achieve the dominant phenotype by expressing the same genes as J. transcriptus males or whether novel brain gene expression patterns have evolved to produce a similar behavioral phenotype in the females of J. marlieri. This study used cDNA microarrays to investigate whether female J. marlieri and male J. transcriptus show conserved or divergent patterns of brain gene expression. Analysis of microarray data in both species showed certain gene expression patterns associated with sex role independent of gonadal sex and, to a lesser extent, gene expression patterns associated with sex independent of sex role. In general, these data suggest that while there has been substantial divergence in gene expression patterns between J. transcriptus and J. marlieri, we can detect a highly significant overlap for a core set of genes related to aggression in both species. These results suggest that the proximate mechanisms regulating aggressive behavior in J. transcriptus and J. marlieri may be shared. PMID:21900474

  8. A testosterone-related structural brain phenotype predicts aggressive behavior from childhood to adulthood.

    PubMed

    Nguyen, Tuong-Vi; McCracken, James T; Albaugh, Matthew D; Botteron, Kelly N; Hudziak, James J; Ducharme, Simon

    2016-01-01

    Structural covariance, the examination of anatomic correlations between brain regions, has emerged recently as a valid and useful measure of developmental brain changes. Yet the exact biological processes leading to changes in covariance, and the relation between such covariance and behavior, remain largely unexplored. The steroid hormone testosterone represents a compelling mechanism through which this structural covariance may be developmentally regulated in humans. Although steroid hormone receptors can be found throughout the central nervous system, the amygdala represents a key target for testosterone-specific effects, given its high density of androgen receptors. In addition, testosterone has been found to impact cortical thickness (CTh) across the whole brain, suggesting that it may also regulate the structural relationship, or covariance, between the amygdala and CTh. Here, we examined testosterone-related covariance between amygdala volumes and whole-brain CTh, as well as its relationship to aggression levels, in a longitudinal sample of children, adolescents, and young adults 6-22 years old. We found: (1) testosterone-specific modulation of the covariance between the amygdala and medial prefrontal cortex (mPFC); (2) a significant relationship between amygdala-mPFC covariance and levels of aggression; and (3) mediation effects of amygdala-mPFC covariance on the relationship between testosterone and aggression. These effects were independent of sex, age, pubertal stage, estradiol levels and anxious-depressed symptoms. These findings are consistent with prior evidence that testosterone targets the neural circuits regulating affect and impulse regulation, and show, for the first time in humans, how androgen-dependent organizational effects may regulate a very specific, aggression-related structural brain phenotype from childhood to young adulthood. PMID:26431805

  9. IMP2/p62 induces genomic instability and an aggressive hepatocellular carcinoma phenotype.

    PubMed

    Kessler, S M; Laggai, S; Barghash, A; Schultheiss, C S; Lederer, E; Artl, M; Helms, V; Haybaeck, J; Kiemer, A K

    2015-01-01

    Hepatocellular carcinoma (HCC) represents the third leading cause of cancer-related deaths and commonly develops in inflammatory environments. The IGF2 mRNA-binding protein IMP2-2/IGF2BP2-2/p62 was originally identified as an autoantigen in HCC. Aim of this study was to investigate a potential pathophysiological role of p62 in hepatocarcinogenesis. Human HCC tissue showed overexpression of IMP2, which strongly correlated with the fetal markers AFP and DLK1/Pref-1/FA-1 and was particularly elevated in tumors with stem-like features and hypervascularization. Molecular classification of IMP2-overexpressing tumors revealed an aggressive phenotype. Livers of mice overexpressing the IMP2 splice variant p62 highly expressed the stem cell marker DLK1 and secreted DLK1 into the blood. p62 was oncogenic: diethylnitrosamine (DEN)-treated p62 transgenic mice exhibited a higher tumor incidence and multiplicity than wild types. Tumors of transgenics showed a more aggressive and stem-like phenotype and displayed more oncogenic chromosomal aberrations determined with aCGH analysis. DEN-treated p62 transgenic mice exhibited distinct signs of inflammation, such as inflammatory cytokine expression and oxidative stress markers, that is, thiobarbituric acid-reactive substance (TBARS) levels. Reactive oxygen species (ROS) production was elevated in HepG2 cells, which either overexpressed p62 or were treated with DLK1. p62 induced this ROS production by a DLK1-dependent induction and activation of the small Rho-GTPase RAC1, activating NADPH oxidase and being overexpressed in human HCC. Our data indicate that p62/IMP2 promotes hepatocarcinogenesis by an amplification of inflammation. PMID:26426686

  10. IMP2/p62 induces genomic instability and an aggressive hepatocellular carcinoma phenotype

    PubMed Central

    Kessler, S M; Laggai, S; Barghash, A; Schultheiss, C S; Lederer, E; Artl, M; Helms, V; Haybaeck, J; Kiemer, A K

    2015-01-01

    Hepatocellular carcinoma (HCC) represents the third leading cause of cancer-related deaths and commonly develops in inflammatory environments. The IGF2 mRNA-binding protein IMP2-2/IGF2BP2-2/p62 was originally identified as an autoantigen in HCC. Aim of this study was to investigate a potential pathophysiological role of p62 in hepatocarcinogenesis. Human HCC tissue showed overexpression of IMP2, which strongly correlated with the fetal markers AFP and DLK1/Pref-1/FA-1 and was particularly elevated in tumors with stem-like features and hypervascularization. Molecular classification of IMP2-overexpressing tumors revealed an aggressive phenotype. Livers of mice overexpressing the IMP2 splice variant p62 highly expressed the stem cell marker DLK1 and secreted DLK1 into the blood. p62 was oncogenic: diethylnitrosamine (DEN)-treated p62 transgenic mice exhibited a higher tumor incidence and multiplicity than wild types. Tumors of transgenics showed a more aggressive and stem-like phenotype and displayed more oncogenic chromosomal aberrations determined with aCGH analysis. DEN-treated p62 transgenic mice exhibited distinct signs of inflammation, such as inflammatory cytokine expression and oxidative stress markers, that is, thiobarbituric acid-reactive substance (TBARS) levels. Reactive oxygen species (ROS) production was elevated in HepG2 cells, which either overexpressed p62 or were treated with DLK1. p62 induced this ROS production by a DLK1-dependent induction and activation of the small Rho-GTPase RAC1, activating NADPH oxidase and being overexpressed in human HCC. Our data indicate that p62/IMP2 promotes hepatocarcinogenesis by an amplification of inflammation. PMID:26426686

  11. A three-dimensional engineered tumour for spatial snapshot analysis of cell metabolism and phenotype in hypoxic gradients.

    PubMed

    Rodenhizer, Darren; Gaude, Edoardo; Cojocari, Dan; Mahadevan, Radhakrishnan; Frezza, Christian; Wouters, Bradly G; McGuigan, Alison P

    2016-02-01

    The profound metabolic reprogramming that occurs in cancer cells has been investigated primarily in two-dimensional cell cultures, which fail to recapitulate spatial aspects of cell-to-cell interactions as well as tissue gradients present in three-dimensional tumours. Here, we describe an engineered model to assemble three-dimensional tumours by rolling a scaffold-tumour composite strip. By unrolling the strip, the model can be rapidly disassembled for snapshot analysis, allowing spatial mapping of cell metabolism in concert with cell phenotype. We also show that the establishment of oxygen gradients within samples that are shaped by oxygen-dependent signalling pathways, as well as the consequential variations in cell growth, response to hypoxic gradients extending from normoxia to severe hypoxia, and therapy responsiveness, are consistent with those of tumours in vivo. Moreover, by using liquid chromatography tandem mass spectrometry, we mapped cellular metabolism and identified spatially defined metabolic signatures of cancer cells to reveal both known and novel metabolic responses to hypoxia. PMID:26595121

  12. A three-dimensional engineered tumour for spatial snapshot analysis of cell metabolism and phenotype in hypoxic gradients

    NASA Astrophysics Data System (ADS)

    Rodenhizer, Darren; Gaude, Edoardo; Cojocari, Dan; Mahadevan, Radhakrishnan; Frezza, Christian; Wouters, Bradly G.; McGuigan, Alison P.

    2016-02-01

    The profound metabolic reprogramming that occurs in cancer cells has been investigated primarily in two-dimensional cell cultures, which fail to recapitulate spatial aspects of cell-to-cell interactions as well as tissue gradients present in three-dimensional tumours. Here, we describe an engineered model to assemble three-dimensional tumours by rolling a scaffold-tumour composite strip. By unrolling the strip, the model can be rapidly disassembled for snapshot analysis, allowing spatial mapping of cell metabolism in concert with cell phenotype. We also show that the establishment of oxygen gradients within samples that are shaped by oxygen-dependent signalling pathways, as well as the consequential variations in cell growth, response to hypoxic gradients extending from normoxia to severe hypoxia, and therapy responsiveness, are consistent with those of tumours in vivo. Moreover, by using liquid chromatography tandem mass spectrometry, we mapped cellular metabolism and identified spatially defined metabolic signatures of cancer cells to reveal both known and novel metabolic responses to hypoxia.

  13. Coexpression analysis of large cancer datasets provides insight into the cellular phenotypes of the tumour microenvironment

    PubMed Central

    2013-01-01

    Background Biopsies taken from individual tumours exhibit extensive differences in their cellular composition due to the inherent heterogeneity of cancers and vagaries of sample collection. As a result genes expressed in specific cell types, or associated with certain biological processes are detected at widely variable levels across samples in transcriptomic analyses. This heterogeneity also means that the level of expression of genes expressed specifically in a given cell type or process, will vary in line with the number of those cells within samples or activity of the pathway, and will therefore be correlated in their expression. Results Using a novel 3D network-based approach we have analysed six large human cancer microarray datasets derived from more than 1,000 individuals. Based upon this analysis, and without needing to isolate the individual cells, we have defined a broad spectrum of cell-type and pathway-specific gene signatures present in cancer expression data which were also found to be largely conserved in a number of independent datasets. Conclusions The conserved signature of the tumour-associated macrophage is shown to be largely-independent of tumour cell type. All stromal cell signatures have some degree of correlation with each other, since they must all be inversely correlated with the tumour component. However, viewed in the context of established tumours, the interactions between stromal components appear to be multifactorial given the level of one component e.g. vasculature, does not correlate tightly with another, such as the macrophage. PMID:23845084

  14. Acquisition of Paclitaxel Resistance Is Associated With a More Aggressive and Invasive Phenotype in Prostate Cancer

    PubMed Central

    Kim, John J.; Yin, Bo; Christudass, Christhunesa S.; Terada, Naoki; Rajagopalan, Krithika; Fabry, Ben; Lee, Danielle Y.; Shiraishi, Takumi; Getzenberg, Robert H.; Veltri, Robert W.; An, Steven S.; Mooney, Steven M.

    2014-01-01

    Drug resistance is a major limitation to the successful treatment of advanced prostate cancer (PCa). Patients who have metastatic, castration-resistant PCa (mCRPC) are treated with chemotherapeutics. However, these standard therapy modalities culminate in the development of resistance. We established paclitaxel resistance in a classic, androgen-insensitive mCRPC cell line (DU145) and, using a suite of molecular and biophysical methods, characterized the structural and functional changes in vitro and in vivo that are associated with the development of drug resistance. After acquiring paclitaxel-resistance, cells exhibited an abnormal nuclear morphology with extensive chromosomal content, an increase in stiffness, and faster cytoskeletal remodeling dynamics. Compared with the parental DU145, paclitaxel-resistant (DU145-TxR) cells became highly invasive and motile in vitro, exercised greater cell traction forces, and formed larger and rapidly growing tumors in mouse xenografts. Furthermore, DU145-TxR cells showed a discrete loss of keratins but a distinct gain of ZEB1, Vimentin and Snail, suggesting an epithelial-to-mesenchymal transition. These findings demonstrate, for the first time, that paclitaxel resistance in PCa is associated with a trans-differentiation of epithelial cell machinery that enables more aggressive and invasive phenotype and portend new strategies for developing novel biomarkers and effective treatment modalities for PCa patients. PMID:23192682

  15. Identification of a novel BET bromodomain inhibitor-sensitive, gene regulatory circuit that controls Rituximab response and tumour growth in aggressive lymphoid cancers

    PubMed Central

    Emadali, Anouk; Rousseaux, Sophie; Bruder-Costa, Juliana; Rome, Claire; Duley, Samuel; Hamaidia, Sieme; Betton, Patricia; Debernardi, Alexandra; Leroux, Dominique; Bernay, Benoit; Kieffer-Jaquinod, Sylvie; Combes, Florence; Ferri, Elena; McKenna, Charles E; Petosa, Carlo; Bruley, Christophe; Garin, Jérôme; Ferro, Myriam; Gressin, Rémy; Callanan, Mary B; Khochbin, Saadi

    2013-01-01

    Immuno-chemotherapy elicit high response rates in B-cell non-Hodgkin lymphoma but heterogeneity in response duration is observed, with some patients achieving cure and others showing refractory disease or relapse. Using a transcriptome-powered targeted proteomics screen, we discovered a gene regulatory circuit involving the nuclear factor CYCLON which characterizes aggressive disease and resistance to the anti-CD20 monoclonal antibody, Rituximab, in high-risk B-cell lymphoma. CYCLON knockdown was found to inhibit the aggressivity of MYC-overexpressing tumours in mice and to modulate gene expression programs of biological relevance to lymphoma. Furthermore, CYCLON knockdown increased the sensitivity of human lymphoma B cells to Rituximab in vitro and in vivo. Strikingly, this effect could be mimicked by in vitro treatment of lymphoma B cells with a small molecule inhibitor for BET bromodomain proteins (JQ1). In summary, this work has identified CYCLON as a new MYC cooperating factor that autonomously drives aggressive tumour growth and Rituximab resistance in lymphoma. This resistance mechanism is amenable to next-generation epigenetic therapy by BET bromodomain inhibition, thereby providing a new combination therapy rationale for high-risk lymphoma. The nuclear factor CYCLON is a new MYC cooperating factor that drives tumor growth and Rituximab resistance in lymphoma. This resistance mechanism can be targeted by next-generation epigenetic therapy by BET bromodomain inhibition downstream of MYC. PMID:23828858

  16. DNA Hypomethylation-Mediated Overexpression of Carbonic Anhydrase 9 Induces an Aggressive Phenotype in Ovarian Cancer Cells

    PubMed Central

    Sung, Hye Youn

    2014-01-01

    Purpose Both genetic and epigenetic alterations can lead to abnormal expression of metastasis-regulating genes in tumor cells. Recent studies suggest that aberrant epigenetic alterations, followed by differential gene expression, leads to an aggressive cancer cell phenotype. We examined epigenetically regulated genes that are involved in ovarian cancer metastasis. Materials and Methods We developed SK-OV-3 human ovarian carcinoma cell xenografts in mice. We compared the mRNA expression and DNA methylation profiles of metastatic tissues to those of the original SK-OV-3 cell line. Results Metastatic implants showed increased mRNA expression of the carbonic anhydrase 9 (CA9) gene and hypomethylation at CpG sites in the CA9 promoter. Treatment of wild-type SK-OV-3 cells with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine reduced methylation of the CA9 promoter and increased CA9 mRNA expression. Eight CpGs, which were located at positions -197, -74, -19, -6, +4, +13, +40, and +86, relative to the transcription start site, were hypomethylated in metastatic tumor implants, compared to that of wild-type SK-OV-3. Overexpression of CA9 induced an aggressive phenotype, including increased invasiveness and migration, in SK-OV-3 cells. Conclusion Alterations in the DNA methylation profile of the CA9 promoter were correlated with a more aggressive phenotype in ovarian cancer cells. PMID:25323905

  17. Nuclear Morphometry Identifies a Distinct Aggressive Cellular Phenotype in Cutaneous Squamous Cell Carcinoma

    PubMed Central

    Glazer, Evan S.; Bartels, Peter H.; Prasad, Anil R.; Yozwiak, Michael L.; Bartels, Hubert G.; Einspahr, Janine G.; Alberts, David S.; Krouse, Robert S.

    2011-01-01

    By identifying aggressive cutaneous squamous cell carcinoma (cSCC) in patients who are at high risk for recurrences or second primaries after resection, intensive surveillance and therapy may decrease morbidity and mortality. We investigated the role of nuclear morphometry (karyometry) in differentiating between aggressive and nonaggressive cSCC. We retrospectively analyzed cSCC lesions from 40 male patients. 22 patients had evidence of aggressive cSCC (local/regional recurrence or a second primary cSCC), and 18 patients were identified with similar ages and sites of disease as control patients with nonaggressive cSCC (no evidence of recurrence, metastasis, or second primary). We performed karyometric analysis to identify nuclear features that discriminate between aggressive and nonaggressive cSCC nuclei. We used statistically significant differences (Kruskal-Wallis test P < 0.0001) to compose a quantitative aggressive classification score (proportion of aggressive nuclei from 0% to 100%). For comparisons, we used Fisher’s exact test or Student t test. The mean age was 79 ± 7 years for aggressive cSCC and 80 ± 9 years for nonaggressive cSCC (P = 0.66). We analyzed a mean of 96 nuclei in each group. The mean classification score for aggressive cSCC was significantly higher (69% ± 6%) than for nonaggressive cSCC (28% ± 5%, P = 0.00002). Overall, the classification score accurately categorized 80% of our patients (P = 0.0004). In most patients, karyometry differentiated between aggressive and nonaggressive cSCC. We found that classification scores, which provide information on individual lesions, could be used for risk stratification. PMID:21636541

  18. Physical nanoscale conduit-mediated communication between tumour cells and the endothelium modulates endothelial phenotype.

    PubMed

    Connor, Yamicia; Tekleab, Sarah; Nandakumar, Shyama; Walls, Cherelle; Tekleab, Yonatan; Husain, Amjad; Gadish, Or; Sabbisetti, Venkata; Kaushik, Shelly; Sehrawat, Seema; Kulkarni, Ashish; Dvorak, Harold; Zetter, Bruce; R Edelman, Elazer; Sengupta, Shiladitya

    2015-01-01

    Metastasis is a major cause of mortality and remains a hurdle in the search for a cure for cancer. Not much is known about metastatic cancer cells and endothelial cross-talk, which occurs at multiple stages during metastasis. Here we report a dynamic regulation of the endothelium by cancer cells through the formation of nanoscale intercellular membrane bridges, which act as physical conduits for transfer of microRNAs. The communication between the tumour cell and the endothelium upregulates markers associated with pathological endothelium, which is reversed by pharmacological inhibition of these nanoscale conduits. These results lead us to define the notion of 'metastatic hijack': cancer cell-induced transformation of healthy endothelium into pathological endothelium via horizontal communication through the nanoscale conduits. Pharmacological perturbation of these nanoscale membrane bridges decreases metastatic foci in vivo. Targeting these nanoscale membrane bridges may potentially emerge as a new therapeutic opportunity in the management of metastatic cancer. PMID:26669454

  19. Physical nanoscale conduit-mediated communication between tumour cells and the endothelium modulates endothelial phenotype

    PubMed Central

    Connor, Yamicia; Tekleab, Sarah; Nandakumar, Shyama; Walls, Cherelle; Tekleab, Yonatan; Husain, Amjad; Gadish, Or; Sabbisetti, Venkata; Kaushik, Shelly; Sehrawat, Seema; Kulkarni, Ashish; Dvorak, Harold; Zetter, Bruce; R. Edelman, Elazer; Sengupta, Shiladitya

    2015-01-01

    Metastasis is a major cause of mortality and remains a hurdle in the search for a cure for cancer. Not much is known about metastatic cancer cells and endothelial cross-talk, which occurs at multiple stages during metastasis. Here we report a dynamic regulation of the endothelium by cancer cells through the formation of nanoscale intercellular membrane bridges, which act as physical conduits for transfer of microRNAs. The communication between the tumour cell and the endothelium upregulates markers associated with pathological endothelium, which is reversed by pharmacological inhibition of these nanoscale conduits. These results lead us to define the notion of ‘metastatic hijack': cancer cell-induced transformation of healthy endothelium into pathological endothelium via horizontal communication through the nanoscale conduits. Pharmacological perturbation of these nanoscale membrane bridges decreases metastatic foci in vivo. Targeting these nanoscale membrane bridges may potentially emerge as a new therapeutic opportunity in the management of metastatic cancer. PMID:26669454

  20. Candidate genes contributing to the aggressive phenotype of mantle cell lymphoma

    PubMed Central

    Henson, Sarah E.; Morford, Travis; Stein, Mary-Pat; Wall, Randolph; Malone, Cindy S.

    2012-01-01

    Mantle cell lymphoma and small lymphocytic lymphoma are lymphocyte cancers that have similar morphologies and a common age of onset. Mantle cell lymphoma is generally an aggressive B cell lymphoma with a short median survival time, whereas small lymphocytic lymphoma is typically an indolent B cell lymphoma with a prolonged median survival time. Using primary tumor samples in bidirectional suppression subtractive hybridization, we identified genes with differential expression in an aggressive mantle cell lymphoma versus an indolent small lymphocytic lymphoma. “Virtual” Northern blot analyses of multiple lymphoma samples confirmed that a set of genes was preferentially expressed in aggressive mantle cell lymphoma compared to indolent small lymphocytic lymphoma. These analyses identified mantle cell lymphoma-specific genes that may be involved in the aggressive behavior of mantle cell lymphoma and possibly other aggressive human lymphomas. Interestingly, most of these differentially-expressed genes have not been identified using other techniques, highlighting the unique ability of suppression subtractive hybridization to identify potentially rare or low expression genes. PMID:21145576

  1. Prostate stromal cell proteomics analysis discriminates normal from tumour reactive stromal phenotypes

    PubMed Central

    Webber, Jason P.; Spary, Lisa K.; Mason, Malcolm D.; Tabi, Zsuzsanna; Brewis, Ian A.; Clayton, Aled

    2016-01-01

    Changes within interstitial stromal compartments often accompany carcinogenesis, and this is true of prostate cancer. Typically, the tissue becomes populated by myofibroblasts that can promote progression. Not all myofibroblasts exhibit the same negative influence, however, and identifying the aggressive form of myofibroblast may provide useful information at diagnosis. A means of molecularly defining such myofibroblasts is unknown. We compared protein profiles of normal and diseased stroma isolated from prostate cancer patients to identify discriminating hallmarks of disease-associated stroma. We included the stimulation of normal stromal cells with known myofibroblast inducers namely soluble TGFβ and exosome-associated-TGFβ and compared the function and protein profiles arising. In all 6-patients examined, diseased stroma exhibited a pro-angiogenic influence on endothelial cells, generating large multicellular vessel-like structures. Identical structures were apparent following stimulation of normal stroma with exosomes (5/6 patients), but TGFβ-stimulation generated a non-angiogenic stroma. Proteomics highlighted disease-related cytoskeleton alterations such as elevated Transgelin (TAGLN). Many of these were also changed following TGFβ or exosome stimulation and did not well discriminate the nature of the stimulus. Soluble TGFβ, however triggered differential expression of proteins related to mitochondrial function including voltage dependent ion channels VDAC1 and 2, and this was not found in the other stromal types studied. Surprisingly, Aldehyde Dehydrogenase (ALDH1A1), a stem-cell associated protein was detected in normal stromal cells and found to decrease in disease. In summary, we have discovered a set of proteins that contribute to defining disease-associated myofibroblasts, and emphasise the similarity between exosome-generated myofibroblasts and those naturally arising in situ. PMID:26934553

  2. The ETS family member GABPα modulates androgen receptor signalling and mediates an aggressive phenotype in prostate cancer.

    PubMed

    Sharma, Naomi L; Massie, Charlie E; Butter, Falk; Mann, Matthias; Bon, Helene; Ramos-Montoya, Antonio; Menon, Suraj; Stark, Rory; Lamb, Alastair D; Scott, Helen E; Warren, Anne Y; Neal, David E; Mills, Ian G

    2014-06-01

    In prostate cancer (PC), the androgen receptor (AR) is a key transcription factor at all disease stages, including the advanced stage of castrate-resistant prostate cancer (CRPC). In the present study, we show that GABPα, an ETS factor that is up-regulated in PC, is an AR-interacting transcription factor. Expression of GABPα enables PC cell lines to acquire some of the molecular and cellular characteristics of CRPC tissues as well as more aggressive growth phenotypes. GABPα has a transcriptional role that dissects the overlapping cistromes of the two most common ETS gene fusions in PC: overlapping significantly with ETV1 but not with ERG target genes. GABPα bound predominantly to gene promoters, regulated the expression of one-third of AR target genes and modulated sensitivity to AR antagonists in hormone responsive and castrate resistant PC models. This study supports a critical role for GABPα in CRPC and reveals potential targets for therapeutic intervention.

  3. 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

  4. Decrease in drug accumulation and in tumour aggressiveness marker expression in a fenretinide-induced resistant ovarianumour cell line

    PubMed Central

    Appierto, V; Cavadini, E; Pergolizzi, R; Cleris, L; Lotan, R; Canevari, S; Formelli, F

    2001-01-01

    We investigated whether the efficacy of fenretinide (HPR) against ovarian tumours may be limited by induction of resistance. The human ovarian carcinoma cell line A2780, which is sensitive to a pharmacologically achievable HPR concentration (IC 50= 1 μM), became 10-fold more resistant after exposure to increasing HPR concentrations. The cells (A2780/HPR) did not show cross-resistance to the synthetic retinoid 6-[3-adamantyl-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) and were not sensitive, similarly to the parent line, to all- trans -retinoic acid, 13- cis -retinoic acid or N-(4-methoxyphenyl)retinamide. A2780/HPR cells showed, compared to parental cells, a 3-fold reduction in colony-forming ability in agar. The development of HPR resistance was associated with a marked increase in retinoic acid receptor β (RARβ) mRNA and protein levels, which decreased, together with drug resistance, after drug removal. The expression of cell surface molecules associated with tumour progression including HER-2, laminin receptor and β1 integrin was markedly reduced. The increase in the levels of reactive oxygen species is not involved in HPR-resistance because it was similar in parental and resistant cells. Conversely differences in pharmacokinetics may account for resistance because, in A2780/HPR cells, intracellular peak drug levels were 2 times lower than in A2780 cells and an as yet unidentified polar metabolite was present. These data suggest that acquired resistance to HPR is associated with changes in marker expression, suggestive of a more differentiated status and may be explained, at least in part, by reduced drug accumulation and increased metabolism. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11384104

  5. 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.

  6. An Evolutionary Hybrid Cellular Automaton Model of Solid Tumour Growth

    PubMed Central

    Gerlee, P.; Anderson, A.R.A.

    2007-01-01

    We propose a cellular automaton model of solid tumour growth, in which each cell is equipped with a micro-environment response network. This network is modelled using a feed-forward artificial neural network, that takes environmental variables as an input and from these determines the cellular behaviour as the output. The response of the network is determined by connection weights and thresholds in the network, which are subject to mutations when the cells divide. As both available space and nutrients are limited resources for the tumour this gives rise to clonal evolution where only the fittest cells survive. Using this approach we have investigated the impact of the tissue oxygen concentration on the growth and evolutionary dynamics of the tumour. The results show that the oxygen concentration affects the selection pressure, cell population diversity and morphology of the tumour. A low oxygen concentration in the tissue gives rise to a tumour with a fingered morphology that contains aggressive phenotypes with a small apoptotic potential, while a high oxygen concentration in the tissue gives rise to a tumour with a round morphology containing less evolved phenotypes. The tissue oxygen concentration thus affects the tumour at both the morphological level and on the phenotype level. PMID:17374383

  7. Transcriptomic analysis identified up-regulation of a solute carrier transporter and UDP glucuronosyltransferases in dogs with aggressive cutaneous mast cell tumours.

    PubMed

    Giantin, Mery; Baratto, Chiara; Marconato, Laura; Vascellari, Marta; Mutinelli, Franco; Dacasto, Mauro; Granato, Anna

    2016-06-01

    Gene expression analyses have been recently used in cancer research to identify genes associated with tumorigenesis and potential prognostic markers or therapeutic targets. In the present study, the transcriptome of dogs that had died because of mast cell tumours (MCTs) was characterised to identify a fingerprint having significant influence on prognosis determination and treatment selection. A dataset (GSE50433) obtained using a commercial canine DNA microarray platform was used. The transcriptome of seven biopsies obtained from dogs with histologically confirmed, surgically removed MCTs, treated with chemotherapy, and dead for MCT-related causes, was compared with the transcriptional portrait of 40 samples obtained from dogs with histologically confirmed, surgically removed MCTs and that were still alive at the end of the follow-up period. Among the differentially expressed genes (DEGs), eight transcripts were validated by quantitative real time PCR and their mRNA levels were measured in a cohort of 22 additional MCTs. Statistical analysis identified 375 DEGs (fold change 2, false discovery rate 5%). The functional annotation analysis indicated that the DEGs were associated with drug metabolism and cell cycle pathways. Particularly, members of solute carrier transporter (SLC) and UDP glucuronosyltransferase (UGT) gene families were identified as dysregulated. Principal component analysis (PCA) of the 22 additional MCTs identified the separate cluster dogs dead for MCT-related causes. SLCs and UGTs have been recently recognised in human cancer as important key factors in tumour progression and chemo-resistance. An in-depth analysis of their roles in aggressive canine MCT is warranted in future studies. PMID:27256023

  8. Conservation in Mammals of Genes Associated with Aggression-Related Behavioral Phenotypes in Honey Bees

    PubMed Central

    Robinson, Gene E.; Jakobsson, Eric

    2016-01-01

    The emerging field of sociogenomics explores the relations between social behavior and genome structure and function. An important question is the extent to which associations between social behavior and gene expression are conserved among the Metazoa. Prior experimental work in an invertebrate model of social behavior, the honey bee, revealed distinct brain gene expression patterns in African and European honey bees, and within European honey bees with different behavioral phenotypes. The present work is a computational study of these previous findings in which we analyze, by orthology determination, the extent to which genes that are socially regulated in honey bees are conserved across the Metazoa. We found that the differentially expressed gene sets associated with alarm pheromone response, the difference between old and young bees, and the colony influence on soldier bees, are enriched in widely conserved genes, indicating that these differences have genomic bases shared with many other metazoans. By contrast, the sets of differentially expressed genes associated with the differences between African and European forager and guard bees are depleted in widely conserved genes, indicating that the genomic basis for this social behavior is relatively specific to honey bees. For the alarm pheromone response gene set, we found a particularly high degree of conservation with mammals, even though the alarm pheromone itself is bee-specific. Gene Ontology identification of human orthologs to the strongly conserved honey bee genes associated with the alarm pheromone response shows overrepresentation of protein metabolism, regulation of protein complex formation, and protein folding, perhaps associated with remodeling of critical neural circuits in response to alarm pheromone. We hypothesize that such remodeling may be an adaptation of social animals to process and respond appropriately to the complex patterns of conspecific communication essential for social organization

  9. Conservation in Mammals of Genes Associated with Aggression-Related Behavioral Phenotypes in Honey Bees.

    PubMed

    Liu, Hui; Robinson, Gene E; Jakobsson, Eric

    2016-06-01

    The emerging field of sociogenomics explores the relations between social behavior and genome structure and function. An important question is the extent to which associations between social behavior and gene expression are conserved among the Metazoa. Prior experimental work in an invertebrate model of social behavior, the honey bee, revealed distinct brain gene expression patterns in African and European honey bees, and within European honey bees with different behavioral phenotypes. The present work is a computational study of these previous findings in which we analyze, by orthology determination, the extent to which genes that are socially regulated in honey bees are conserved across the Metazoa. We found that the differentially expressed gene sets associated with alarm pheromone response, the difference between old and young bees, and the colony influence on soldier bees, are enriched in widely conserved genes, indicating that these differences have genomic bases shared with many other metazoans. By contrast, the sets of differentially expressed genes associated with the differences between African and European forager and guard bees are depleted in widely conserved genes, indicating that the genomic basis for this social behavior is relatively specific to honey bees. For the alarm pheromone response gene set, we found a particularly high degree of conservation with mammals, even though the alarm pheromone itself is bee-specific. Gene Ontology identification of human orthologs to the strongly conserved honey bee genes associated with the alarm pheromone response shows overrepresentation of protein metabolism, regulation of protein complex formation, and protein folding, perhaps associated with remodeling of critical neural circuits in response to alarm pheromone. We hypothesize that such remodeling may be an adaptation of social animals to process and respond appropriately to the complex patterns of conspecific communication essential for social organization

  10. Conservation in Mammals of Genes Associated with Aggression-Related Behavioral Phenotypes in Honey Bees.

    PubMed

    Liu, Hui; Robinson, Gene E; Jakobsson, Eric

    2016-06-01

    The emerging field of sociogenomics explores the relations between social behavior and genome structure and function. An important question is the extent to which associations between social behavior and gene expression are conserved among the Metazoa. Prior experimental work in an invertebrate model of social behavior, the honey bee, revealed distinct brain gene expression patterns in African and European honey bees, and within European honey bees with different behavioral phenotypes. The present work is a computational study of these previous findings in which we analyze, by orthology determination, the extent to which genes that are socially regulated in honey bees are conserved across the Metazoa. We found that the differentially expressed gene sets associated with alarm pheromone response, the difference between old and young bees, and the colony influence on soldier bees, are enriched in widely conserved genes, indicating that these differences have genomic bases shared with many other metazoans. By contrast, the sets of differentially expressed genes associated with the differences between African and European forager and guard bees are depleted in widely conserved genes, indicating that the genomic basis for this social behavior is relatively specific to honey bees. For the alarm pheromone response gene set, we found a particularly high degree of conservation with mammals, even though the alarm pheromone itself is bee-specific. Gene Ontology identification of human orthologs to the strongly conserved honey bee genes associated with the alarm pheromone response shows overrepresentation of protein metabolism, regulation of protein complex formation, and protein folding, perhaps associated with remodeling of critical neural circuits in response to alarm pheromone. We hypothesize that such remodeling may be an adaptation of social animals to process and respond appropriately to the complex patterns of conspecific communication essential for social organization.

  11. Acquired resistance to zoledronic acid and the parallel acquisition of an aggressive phenotype are mediated by p38-MAP kinase activation in prostate cancer cells

    PubMed Central

    Milone, M R; Pucci, B; Bruzzese, F; Carbone, C; Piro, G; Costantini, S; Capone, F; Leone, A; Di Gennaro, E; Caraglia, M; Budillon, A

    2013-01-01

    resistance, as well as in the acquisition of a more aggressive and invasive phenotype. PMID:23703386

  12. Hypoxia-induced autophagic response is associated with aggressive phenotype and elevated incidence of metastasis in orthotopic immunocompetent murine models of head and neck squamous cell carcinomas (HNSCC)

    PubMed Central

    Vigneswaran, Nadarajah; Wu, Jean; Song, Anren; Annapragada, Ananth; Zacharias, Wolfgang

    2011-01-01

    Hypoxia confers resistance to chemoradiation therapy and promotes metastasis in head and neck squamous cell carcinomas (HNSCC). We investigated the effects of hypoxia in tumor phenotype using immunocompetent murine HNSCC models. Balb/c mice were injected intraorally with murine squamous cell carcinoma cells LY-2 and B4B8. Intratumoral hypoxia fraction was evaluated by the immunohistochemical detection of hypoxic probe pimonidazole and carbonic anhydrase IX (CAIX). Tumor cell apoptosis and autophagy in hypoxic areas of these tumors were examined immunohistochemially. Hypoxia-induced apoptotic and autophagic responses in vitro were examined by treating LY2 cells with CoCl2. B4B8 tumors exhibited a non-aggressive phenotype characterized by its slow growth rate and the lack of metastatic spread. LY2 tumors demonstrated an aggressive phenotype characterized by rapid growth rate with regional and distant metastasis. Intratumoral hypoxia fraction in B4B8 tumors was significantly lower than LY2 tumors. Hypoxic areas in B4B8 tumors exhibited increased apoptosis rate than LY2 tumors. In contrast, hypoxic areas in LY2 tumors revealed autophagy. Induction of hypoxia in vitro elicited autophagy and not apoptosis in LY2 cells. Induction of autophagy coupled with blockage of apoptosis in hypoxic areas promotes tumor cells survival and confers aggressive phenotype in immunocompetent murine HNSCC models. PMID:21236253

  13. Alterations of the spindle checkpoint pathway in clinicopathologically aggressive CpG island methylator phenotype clear cell renal cell carcinomas

    PubMed Central

    Arai, Eri; Gotoh, Masahiro; Tian, Ying; Sakamoto, Hiromi; Ono, Masaya; Matsuda, Akio; Takahashi, Yoriko; Miyata, Sayaka; Totsuka, Hirohiko; Chiku, Suenori; Komiyama, Motokiyo; Fujimoto, Hiroyuki; Matsumoto, Kenji; Yamada, Tesshi; Yoshida, Teruhiko

    2015-01-01

    CpG‐island methylator phenotype (CIMP)‐positive clear cell renal cell carcinomas (RCCs) are characterized by accumulation of DNA hypermethylation of CpG islands, clinicopathological aggressiveness and poor patient outcome. The aim of this study was to clarify the molecular pathways participating in CIMP‐positive renal carcinogenesis. Genome (whole‐exome and copy number), transcriptome and proteome (two‐dimensional image converted analysis of liquid chromatography‐mass spectrometry) analyses were performed using tissue specimens of 87 CIMP‐negative and 14 CIMP‐positive clear cell RCCs and corresponding specimens of non‐cancerous renal cortex. Genes encoding microtubule‐associated proteins, such as DNAH2, DNAH5, DNAH10, RP1 and HAUS8, showed a 10% or higher incidence of genetic aberrations (non‐synonymous single‐nucleotide mutations and insertions/deletions) in CIMP‐positive RCCs, whereas CIMP‐negative RCCs lacked distinct genetic characteristics. MetaCore pathway analysis of CIMP‐positive RCCs revealed that alterations of mRNA or protein expression were significantly accumulated in six pathways, all participating in the spindle checkpoint, including the “The metaphase checkpoint (p = 1.427 × 10−6),” “Role of Anaphase Promoting Complex in cell cycle regulation (p = 7.444 × 10−6)” and “Spindle assembly and chromosome separation (p = 9.260 × 10−6)” pathways. Quantitative RT‐PCR analysis revealed that mRNA expression levels for genes included in such pathways, i.e., AURKA, AURKB, BIRC5, BUB1, CDC20, NEK2 and SPC25, were significantly higher in CIMP‐positive than in CIMP‐negative RCCs. All CIMP‐positive RCCs showed overexpression of Aurora kinases, AURKA and AURKB, and this overexpression was mainly attributable to increased copy number. These data suggest that abnormalities of the spindle checkpoint pathway participate in CIMP‐positive renal carcinogenesis, and that AURKA and AURKB may be potential

  14. Effect of anti-glycolytic agents on tumour cells in vitro

    NASA Astrophysics Data System (ADS)

    Korshunov, D. A.; Kondakova, I. V.

    2016-08-01

    A metabolic change is one of the tumour hallmarks, which has recently attracted a great amount of attention. One of the main metabolic characteristics of tumour cells is a high level of glycolysis even in the presence of oxygen, known as aerobic glycolysis or the Warburg effect. The energy production is much less in a glycolysis pathway than that in a tricarboxylic acid cycle. The Warburg effect constitutes a fundamental adaptation of tumour cells to a relatively hostile environment, and supports the evolution of aggressive and metastatic phenotypes. As a result, tumour glycolysis may become an attractive target for cancer therapy. Here, we research the effect of potential anticancer agents on tumour cells in vitro. In our study, we found a high sensitivity of tumour cells to anti-glycolityc drugs. In addition, tumour cells are more resistant to the agents studied in comparison with normal cells. We also observed an atypical cooperative interaction of tumour cells in the median lethal dose of drugs. They formed the specific morphological structure of the surviving cells. This behavior is not natural for the culture of tumour cells. Perhaps this is one of the mechanisms of cells' adaptation to the aggressive environment.

  15. 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.

  16. Loss of SOD3 (EcSOD) expression promotes an aggressive phenotype in human pancreatic ductal adenocarcinoma

    PubMed Central

    O’Leary, Brianne R.; Fath, Melissa A.; Bellizzi, Andrew M.; Hrabe, Jennifer E.; Button, Anna M.; Allen, Bryan G.; Case, Adam J.; Altekruse, Sean; Wagner, Brett A.; Buettner, Garry R.; Lynch, Charles F.; Hernandez, Brenda Y.; Cozen, Wendy; Beardsley, Robert A.; Keene, Jeffery; Henry, Michael D.; Domann, Frederick E.; Spitz, Douglas R.; Mezhir, James J.

    2015-01-01

    Purpose Pancreatic ductal adenocarcinoma (PDA) cells are known to produce excessive amounts of reactive oxygen species (ROS), particularly superoxide, which may contribute to the aggressive and refractory nature of this disease. Extracellular superoxide dismutase (EcSOD) is an antioxidant enzyme that catalyzes the dismutation of superoxide in the extracellular environment. The current work tests the hypothesis that EcSOD modulates PDA growth and invasion by modifying the redox balance in PDA. Experimental Design We evaluated the prognostic significance of EcSOD in a human tissue microarray of patients with PDA. EcSOD overexpression was performed in PDA cell lines and animal models of disease. The impact of EcSOD on PDA cell lines was evaluated with Matrigel invasion in combination with a superoxide-specific SOD mimic and a nitric oxide synthase inhibitor to determine the mechanism of action of EcSOD in PDA. Results Loss of EcSOD expression is a common event in PDA, which correlated with worse disease biology. Overexpression of EcSOD in PDA cell lines resulted in decreased invasiveness that appeared to be related to reactions of superoxide with nitric oxide. Pancreatic cancer xenografts overexpressing EcSOD also demonstrated slower growth and peritoneal metastasis. Over-expression of EcSOD or treatment with a superoxide-specific SOD mimic caused significant decreases in PDA cell invasive capacity. Conclusions These results support the hypothesis that loss of EcSOD leads to increased reactions of superoxide with nitric oxide which contributes to the invasive phenotype. These results allow for the speculation that superoxide dismutase mimetics might inhibit PDA progression in human clinical disease. PMID:25634994

  17. Hypoxia-inducible factor 1 alpha is required for the tumourigenic and aggressive phenotype associated with Rab25 expression in ovarian cancer

    PubMed Central

    Gomez-Roman, Natividad; Sahasrabudhe, Neha Mohan; McGregor, Fiona; Chalmers, Anthony J.; Cassidy, Jim; Plumb, Jane

    2016-01-01

    The small GTPase Rab25 has been functionally linked to tumour progression and aggressiveness in ovarian cancer and promotes invasion in three-dimensional environments. This type of migration has been shown to require the expression of the hypoxia-inducible factor 1 alpha (HIF-1α). In this report we demonstrate that Rab25 regulates HIF-1α protein expression in an oxygen independent manner in a panel of cancer cell lines. Regulation of HIF-1α protein expression by Rab25 did not require transcriptional upregulation, but was dependent on de novo protein synthesis through the Erbb2/ERK1/2 and p70S6K/mTOR pathways. Rab25 expression induced HIF-1 transcriptional activity, increased cisplatin resistance, and conferred intraperitoneal growth to the A2780 cell line in immunocompromised mice. Targeting HIF1 activity by silencing HIF-1β re-sensitised cells to cisplatin in vitro and reduced tumour formation of A2780-Rab25 expressing cells in vivo in a mouse ovarian peritoneal carcinomatosis model. Similar effects on cisplatin resistance in vitro and intraperitoneal tumourigenesis in vivo were obtained after HIF1b knockdown in the ovarian cancer cell line SKOV3, which expresses endogenous Rab25 and HIF-1α at atmospheric oxygen concentrations. Our results suggest that Rab25 tumourigenic potential and chemoresistance relies on HIF1 activity in aggressive and metastatic ovarian cancer. Targeting HIF-1 activity may potentially be effective either alone or in combination with standard chemotherapy for aggressive metastatic ovarian cancer. PMID:26967059

  18. Detection of circulating tumour cells with a hybrid (epithelial/mesenchymal) phenotype in patients with metastatic non-small cell lung cancer

    PubMed Central

    Lecharpentier, A; Vielh, P; Perez-Moreno, P; Planchard, D; Soria, J C; Farace, F

    2011-01-01

    Background: Circulating tumour cells (CTC) have a crucial role in metastasis formation and can consistently provide information on patient prognosis. Epithelial-mesenchymal transition (EMT) is considered as an essential process in the metastatic cascade, but there is currently very few data demonstrating directly the existence of the EMT process in CTCs. Methods: CTCs were enriched by blood filtration using ISET (isolation by size of epithelial tumour cells), triply labelled with fluorescent anti-vimentin, anti-pan-keratin antibodies and SYTOX orange nuclear dye, and examined by confocal microscopy in six patients with metastatic non-small cell lung cancer (NSCLC). In parallel, CTCs were morphocytologically identified by an experienced cytopathologist. Results: Isolated or clusters of dual CTCs strongly co-expressing vimentin and keratin were evidenced in all patients (range 5–88/5 ml). CTCs expressing only vimentin were detected in three patients, but were less frequent (range 3–15/5 ml). No CTC expressing only keratin was detected. Conclusion: We showed for the first time the existence of hybrid CTCs with an epithelial/mesenchymal phenotype in patients with NSCLC. Their characterisation should provide further insight on the significance of EMT in CTCs and on the mechanism of metastasis in patients with NSCLC. PMID:21970878

  19. Tumour necrosis factor-α plus interleukin-10 low producer phenotype predicts acute kidney injury and death in intensive care unit patients

    PubMed Central

    Dalboni, M A; Quinto, B M R; Grabulosa, C C; Narciso, R; Monte, J C; Durão, M; Rizzo, L; Cendoroglo, M; Santos, O P; Batista, M C

    2013-01-01

    Genetic polymorphism studies of cytokines may provide an insight into the understanding of acute kidney injury (AKI) and death in intensive care unit (ICU) patients. The aim of this study was to investigate whether the genetic polymorphisms of −308 G < A tumour necrosis factor (TNF)-α, −174 G > C interleukin (IL)-6 and −1082 G > A IL-10 may predispose ICU patients to the development of AKI and/or death. In a prospective nested case–control study, 303 ICU patients and 244 healthy individuals were evaluated. The study group included ICU patients who developed AKI (n = 139) and 164 ICU patients without AKI. The GG genotype of TNF-α (low producer phenotype) was significantly lower in the with AKI than without AKI groups and healthy individuals (55 versus 62 versus 73%, respectively; P = 0·01). When genotypes were stratified into four categories of TNF-α/IL-10 combinations, it was observed that low TNF-α plus low IL-10 producer phenotypes were more prevalent in patients with AKI, renal replacement therapy and death (P < 0·05). In logistic regression analysis, low TNF-α producer plus low IL-10 producer phenotypes remained as independent risk factors for AKI and/or death [odds ratio (OR) = 2·37, 95% confidence interval (CI): 1·16–4·84; P = 0·02] and for renal replacement therapy (RRT) and/or death (OR = 3·82, 95% CI: 1·19–12·23; P = 0·02). In this study, the combination of low TNF-α plus low IL-10 producer phenotypes was an independent risk factor to AKI and/or death and RRT and/or death in critically ill patients. Our results should be validated in a larger prospective study with long-term follow-up to emphasize the combination of these genotypes as potential risk factors to AKI in critically ill patients. PMID:23607333

  20. Phenotypic differences in behavior, physiology and neurochemistry between rats selected for tameness and for defensive aggression towards humans.

    PubMed

    Albert, Frank W; Shchepina, Olesya; Winter, Christine; Römpler, Holger; Teupser, Daniel; Palme, Rupert; Ceglarek, Uta; Kratzsch, Jürgen; Sohr, Reinhard; Trut, Lyudmila N; Thiery, Joachim; Morgenstern, Rudolf; Plyusnina, Irina Z; Schöneberg, Torsten; Pääbo, Svante

    2008-03-01

    To better understand the biology of tameness, i.e. tolerance of human presence and handling, we analyzed two lines of wild-derived rats (Rattus norvegicus) artificially selected for tameness and defensive aggression towards humans. In response to a gloved human hand, tame rats tolerated handling, whereas aggressive rats attacked. Cross-fostering showed that these behavioral differences are not caused by postnatal maternal effects. Tame rats were more active and explorative and exhibited fewer anxiety-related behaviors. They also had smaller adrenal glands, larger spleens and lower levels of serum corticosterone. Blood glucose levels were lower in tame rats, whereas the concentrations of nine amino acids were higher. In the brain, tame rats had lower serotonin and higher taurine levels than aggressive rats. Our findings reinforce the notion that tameness is correlated with differences in stress response and will facilitate future efforts to uncover the genetic basis for animal tameness.

  1. Differential partial activation phenotype and production of tumour necrosis factor-α by conventional dendritic cells in response to lipopolysaccharide in HIV+ viraemic subjects and HIV+ controllers.

    PubMed

    Camacho-Sandoval, R; Del Río Estrada, P M; Rivero-Arrieta, A; Reyes-Terán, G; Bonifaz, L C

    2014-12-01

    HIV(+) subjects are reported to have increased soluble CD14 (sCD14) in plasma, an indicator of microbial translocation. We evaluated if microbial translocation has a differential impact on the activation and function of conventional dendritic cells (cDC) from viraemic HIV(+) subjects and HIV(+) controllers (CTs). The HIV(+) subjects were classified into two groups according to their plasma viral load (pVL): CT and viraemic. Subjects without HIV were included as controls (HIV(-) ). The frequencies and phenotypes of cDC from these subjects were evaluated by multi-parameter flow cytometry. In addition, peripheral blood mononuclear cells (PBMCs) were stimulated with lipopolysaccharide (LPS) or single-stranded RNA40 (ssRNA40), the phenotype of the cDC and the intracellular production of tumour necrosis factor (TNF)-α by the cDC were evaluated by flow cytometry. We observed a partial activation phenotype for the cDC in the viraemic subjects and CTs ex vivo and after LPS activation, which showed differences in the expression of CD40 and CD86. Furthermore, in response to LPS the cDC from the viraemic subjects produced more TNF-α compared to the cDC from CTs. Interestingly, the percentage of TNF-α(+) cDC was found to be correlated positively with the pVL. The partial activation of cDC and the over-production of TNF-α in response to LPS in viraemic HIV(+) subjects might be related to the increased chronic activation observed in these subjects. In contrast, cDC from CTs seem to have a regulated response to LPS, indicating that they respond differently to chronic immune activation. These results may have implications in the development of HIV therapies and vaccines using DC.

  2. Differential partial activation phenotype and production of tumour necrosis factor-α by conventional dendritic cells in response to lipopolysaccharide in HIV+ viraemic subjects and HIV+ controllers

    PubMed Central

    Camacho-Sandoval, R; Del Río Estrada, P M; Rivero-Arrieta, A; Reyes-Terán, G; Bonifaz, L C

    2014-01-01

    HIV+ subjects are reported to have increased soluble CD14 (sCD14) in plasma, an indicator of microbial translocation. We evaluated if microbial translocation has a differential impact on the activation and function of conventional dendritic cells (cDC) from viraemic HIV+ subjects and HIV+ controllers (CTs). The HIV+ subjects were classified into two groups according to their plasma viral load (pVL): CT and viraemic. Subjects without HIV were included as controls (HIV–). The frequencies and phenotypes of cDC from these subjects were evaluated by multi-parameter flow cytometry. In addition, peripheral blood mononuclear cells (PBMCs) were stimulated with lipopolysaccharide (LPS) or single-stranded RNA40 (ssRNA40), the phenotype of the cDC and the intracellular production of tumour necrosis factor (TNF)-α by the cDC were evaluated by flow cytometry. We observed a partial activation phenotype for the cDC in the viraemic subjects and CTs ex vivo and after LPS activation, which showed differences in the expression of CD40 and CD86. Furthermore, in response to LPS the cDC from the viraemic subjects produced more TNF-α compared to the cDC from CTs. Interestingly, the percentage of TNF-α+ cDC was found to be correlated positively with the pVL. The partial activation of cDC and the over-production of TNF-α in response to LPS in viraemic HIV+ subjects might be related to the increased chronic activation observed in these subjects. In contrast, cDC from CTs seem to have a regulated response to LPS, indicating that they respond differently to chronic immune activation. These results may have implications in the development of HIV therapies and vaccines using DC. PMID:25130456

  3. [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.

  4. Functional interaction between acyl-CoA synthetase 4, lipooxygenases and cyclooxygenase-2 in the aggressive phenotype of breast cancer cells.

    PubMed

    Maloberti, Paula M; Duarte, Alejandra B; Orlando, Ulises D; Pasqualini, María E; Solano, Angela R; López-Otín, Carlos; Podestá, Ernesto J

    2010-11-11

    The acyl-CoA synthetase 4 (ACSL4) is increased in breast cancer, colon and hepatocellular carcinoma. ACSL4 mainly esterifies arachidonic acid (AA) into arachidonoyl-CoA, reducing free AA intracellular levels, which is in contradiction with the need for AA metabolites in tumorigenesis. Therefore, the causal role of ACSL4 is still not established. This study was undertaken to determine the role of ACSL4 in AA metabolic pathway in breast cancer cells. The first novel finding is that ACSL4 regulates the expression of cyclooxygenase-2 (COX-2) and the production of prostaglandin in MDA-MB-231 cells. We also found that ACSL4 is significantly up-regulated in the highly aggressive MDA-MB-231 breast cancer cells. In terms of its overexpression and inhibition, ACSL4 plays a causal role in the control of the aggressive phenotype. These results were confirmed by the increase in the aggressive behaviour of MCF-7 cells stably transfected with a Tet-off ACSL4 vector. Concomitantly, another significant finding was that intramitochondrial AA levels are significantly higher in the aggressive cells. Thus, the esterification of AA by ACSL4 compartmentalizes the release of AA in mitochondria, a mechanism that serves to drive the specific lipooxygenase metabolization of the fatty acid. To our knowledge, this is the first report that ACSL4 expression controls both lipooxygenase and cyclooxygenase metabolism of AA. Thus, this functional interaction represents an integrated system that regulates the proliferating and metastatic potential of cancer cells. Therefore, the development of combinatory therapies that profit from the ACSL4, lipooxygenase and COX-2 synergistic action may allow for lower medication doses and avoidance of side effects.

  5. Activation of tumour cell ECM degradation by thrombin-activated platelet membranes: potentially a P-selectin and GPIIb/IIIa-dependent process.

    PubMed

    Pang, J H; Coupland, L A; Freeman, C; Chong, B H; Parish, Christopher R

    2015-06-01

    The promotion of tumour metastasis by platelets may occur through several mechanisms including the induction of a more metastatic phenotype in tumour cells and assisted extravasation of circulating tumour cells. Whilst the mechanisms underlying platelet-assisted extravasation have been extensively studied, much less attention has been paid to the mechanisms underlying platelet promotion of an aggressive phenotype within a tumour cell population. Herein, we demonstrate in vitro that MDA-MB-231 breast carcinoma cells incubated with washed thrombin-activated platelet membranes adopt a Matrigel-degrading phenotype in a dose- and contact time-dependent manner. The same phenotypic change was observed with three other human tumour cell lines of diverse anatomical origin. Moreover, tumour cell lines that had been cultured with washed thrombin-activated platelet membranes had a greater metastatic capacity when injected into mice. This in vivo effect was reliant upon a co-incubation period of >2 h implying a mechanism involving more than platelet membrane binding that occurred within 5 min. Upon further investigation it was found that simultaneous blocking of the platelet-membrane proteins P-selectin and GPIIb/IIIa prevented interactions between platelet membranes and MDA-MB-231 cells but also significantly reduced the ability of tumour cells to degrade Matrigel. These results confirm that platelets induce a more aggressive phenotype in tumour cells but also identify the platelet proteins involved in this effect. P-selectin and GPIIb/IIIa also play a role in assisting tumour cell extravasation and, thus, are ideal targets for the therapeutic intervention of both stages of platelet-assisted metastasis.

  6. siRNA Knockdown of Ribosomal Protein Gene RPL19 Abrogates the Aggressive Phenotype of Human Prostate Cancer

    PubMed Central

    Bee, Alix; Brewer, Daniel; Beesley, Carol; Dodson, Andrew; Forootan, Shiva; Dickinson, Timothy; Gerard, Patricia; Lane, Brian; Yao, Sheng; Cooper, Colin S.; Djamgoz, Mustafa B. A.; Gosden, Christine M.; Ke, Youqiang; Foster, Christopher S.

    2011-01-01

    We provide novel functional data that posttranscriptional silencing of gene RPL19 using RNAi not only abrogates the malignant phenotype of PC-3M prostate cancer cells but is selective with respect to transcription and translation of other genes. Reducing RPL19 transcription modulates a subset of genes, evidenced by gene expression array analysis and Western blotting, but does not compromise cell proliferation or apoptosis in-vitro. However, growth of xenografted tumors containing the knocked-down RPL19 in-vivo is significantly reduced. Analysis of the modulated genes reveals induction of the non-malignant phenotype principally to involve perturbation of networks of transcription factors and cellular adhesion genes. The data provide evidence that extra-ribosomal regulatory functions of RPL19, beyond protein synthesis, are critical regulators of cellular phenotype. Targeting key members of affected networks identified by gene expression analysis raises the possibility of therapeutically stabilizing a benign phenotype generated by modulating the expression of an individual gene and thereafter constraining a malignant phenotype while leaving non-malignant tissues unaffected. PMID:21799931

  7. The occurrence of intracranial rhabdoid tumours in mice depends on temporal control of Smarcb1 inactivation

    PubMed Central

    Han, Zhi-Yan; Richer, Wilfrid; Fréneaux, Paul; Chauvin, Céline; Lucchesi, Carlo; Guillemot, Delphine; Grison, Camille; Lequin, Delphine; Pierron, Gaelle; Masliah-Planchon, Julien; Nicolas, André; Ranchère-Vince, Dominique; Varlet, Pascale; Puget, Stéphanie; Janoueix-Lerosey, Isabelle; Ayrault, Olivier; Surdez, Didier; Delattre, Olivier; Bourdeaut, Franck

    2016-01-01

    Rhabdoid tumours (RTs) are highly aggressive tumours of infancy, frequently localized in the central nervous system (CNS) where they are termed atypical teratoid/rhabdoid tumours (AT/RTs) and characterized by bi-allelic inactivation of the SMARCB1 tumour suppressor gene. In this study, by temporal control of tamoxifen injection in Smarcb1flox/flox;Rosa26-CreERT2 mice, we explore the phenotypes associated with Smarcb1 inactivation at different developmental stages. Injection before E6, at birth or at 2 months of age recapitulates previously described phenotypes including embryonic lethality, hepatic toxicity or development of T-cell lymphomas, respectively. Injection between E6 and E10 leads to high penetrance tumours, mainly intra-cranial, with short delays (median: 3 months). These tumours demonstrate anatomical, morphological and gene expression profiles consistent with those of human AT/RTs. Moreover, intra- and inter-species comparisons of tumours reveal that human and mouse RTs can be split into different entities that may underline the variety of RT cells of origin. PMID:26818002

  8. Maspin as a Tumour Suppressor in Salivary Gland Tumour

    PubMed Central

    Ashok, Nipun; Sheirawan, Mohammad Kinan; Altamimi, Mohammed Alsakran; Alenzi, Faris; Azzeghaiby, Saleh Nasser; Baroudi, Kusai; Nassani, Mohammad Zakaria

    2014-01-01

    Maspin is a protein that belongs to serin protease inhibitor (serpin) superfamily. The purpose of this study was to review the literature concerning the expression of maspin in salivary gland tumours. A literature search was done using MEDLINE, accessed via the National Library of Medicine PubMed interface. Statistical analysis was not done because only seven studies were available in literature, the collected data were different and the results could not be compared. Expression of maspin was down regulated in more aggressive salivary gland tumours. Maspin may function as a tumour suppressor in salivary gland tumours. PMID:25654053

  9. 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

  10. Aggressive local therapy combined with systemic chemotherapy provides long-term control in grade II stage 2 canine mast cell tumour: 21 cases (1999-2012).

    PubMed

    Lejeune, A; Skorupski, K; Frazier, S; Vanhaezebrouck, I; Rebhun, R B; Reilly, C M; Rodriguez, C O

    2015-09-01

    This retrospective case series evaluates the outcome of 21 dogs with grade II stage 2 mast cell tumour (MCT) treated with adequate local therapy and adjuvant systemic chemotherapy (prednisone, vinblastine and CCNU). The median survival for all dogs was 1359 days (range, 188-2340). Median disease-free interval was 2120 days (149-2325 days). Dogs treated with surgery and chemotherapy had shorter survival (median, 1103 days; 188-2010 days) than those that underwent surgery, radiation therapy and chemotherapy as part of their treatment (median, 2056 days; 300-2340 days). Two patients had local recurrence in the radiation field and four patients had de novo MCT. Distant metastasis was not observed in any dogs. The results of this study suggest that, in the presence of loco-regional lymph node metastasis in grade II MCT, the use of prednisone, vinblastine and CCNU after adequate local-regional therapy can provide a median survival in excess of 40 months.

  11. Tumour Cell Heterogeneity

    PubMed Central

    Gay, Laura; Baker, Ann-Marie; Graham, Trevor A.

    2016-01-01

    The population of cells that make up a cancer are manifestly heterogeneous at the genetic, epigenetic, and phenotypic levels. In this mini-review, we summarise the extent of intra-tumour heterogeneity (ITH) across human malignancies, review the mechanisms that are responsible for generating and maintaining ITH, and discuss the ramifications and opportunities that ITH presents for cancer prognostication and treatment. PMID:26973786

  12. Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan

    PubMed Central

    Maishi, Nako; Ohba, Yusuke; Akiyama, Kosuke; Ohga, Noritaka; Hamada, Jun-ichi; Nagao-Kitamoto, Hiroko; Alam, Mohammad Towfik; Yamamoto, Kazuyuki; Kawamoto, Taisuke; Inoue, Nobuo; Taketomi, Akinobu; Shindoh, Masanobu; Hida, Yasuhiro; Hida, Kyoko

    2016-01-01

    Tumour blood vessels are gateways for distant metastasis. Recent studies have revealed that tumour endothelial cells (TECs) demonstrate distinct phenotypes from their normal counterparts. We have demonstrated that features of TECs are different depending on tumour malignancy, suggesting that TECs communicate with surrounding tumour cells. However, the contribution of TECs to metastasis has not been elucidated. Here, we show that TECs actively promote tumour metastasis through a bidirectional interaction between tumour cells and TECs. Co-implantation of TECs isolated from highly metastatic tumours accelerated lung metastases of low metastatic tumours. Biglycan, a small leucine-rich repeat proteoglycan secreted from TECs, activated tumour cell migration via nuclear factor-κB and extracellular signal–regulated kinase 1/2. Biglycan expression was upregulated by DNA demethylation in TECs. Collectively, our results demonstrate that TECs are altered in their microenvironment and, in turn, instigate tumour cells to metastasize, which is a novel mechanism for tumour metastasis. PMID:27295191

  13. Annexin A1 is involved in the acquisition and maintenance of a stem cell-like/aggressive phenotype in prostate cancer cells with acquired resistance to zoledronic acid.

    PubMed

    Bizzarro, Valentina; Belvedere, Raffaella; Milone, Maria Rita; Pucci, Biagio; Lombardi, Rita; Bruzzese, Francesca; Popolo, Ada; Parente, Luca; Budillon, Alfredo; Petrella, Antonello

    2015-09-22

    In this study, we have characterized the role of annexin A1 (ANXA1) in the acquisition and maintenance of stem-like/aggressive features in prostate cancer (PCa) cells comparing zoledronic acid (ZA)-resistant DU145R80 with their parental DU145 cells. ANXA1 is over-expressed in DU145R80 cells and its down-regulation abolishes their resistance to ZA. Moreover, ANXA1 induces DU145 and DU145R80 invasiveness acting through formyl peptide receptors (FPRs). Also, ANXA1 knockdown is able to inhibit epithelial to mesenchymal transition (EMT) and to reduce focal adhesion kinase (FAK) and metalloproteases (MMP)-2/9 expression in PCa cells. DU145R80 show a cancer stem cell (CSC)-like signature with a high expression of CSC markers including CD44, CD133, NANOG, Snail, Oct4 and ALDH7A1 and CSC-related genes as STAT3. Interestingly, ANXA1 knockdown induces these cells to revert from a putative prostate CSC to a more differentiated phenotype resembling DU145 PCa cell signature. Similar results are obtained concerning some drug resistance-related genes such as ATP Binding Cassette G2 (ABCG2) and Lung Resistant Protein (LRP). Our study provides new insights on the role of ANXA1 protein in PCa onset and progression. PMID:26312765

  14. Aggressive local therapy combined with systemic chemotherapy provides long-term control in grade II stage 2 canine mast cell tumour: 21 cases (1999–2012)*

    PubMed Central

    Lejeune, A.; Skorupski, K.; Frazier, S.; Vanhaezebrouck, I.; Rebhun, R. B.; Reilly, C. M.; Rodriguez, C. O.

    2016-01-01

    This retrospective case series evaluates the outcome of 21 dogs with grade II stage 2 mast cell tumour (MCT) treated with adequate local therapy and adjuvant systemic chemotherapy (prednisone, vinblastine and CCNU). The median survival for all dogs was 1359 days (range, 188–2340). Median disease-free interval was 2120 days (149–2325 days). Dogs treated with surgery and chemotherapy had shorter survival (median, 1103 days; 188–2010 days) than those that underwent surgery, radiation therapy and chemotherapy as part of their treatment (median, 2056 days; 300–2340 days). Two patients had local recurrence in the radiation field and four patients had de novo MCT. Distant metastasis was not observed in any dogs. The results of this study suggest that, in the presence of loco-regional lymph node metastasis in grade II MCT, the use of prednisone, vinblastine and CCNU after adequate local-regional therapy can provide a median survival in excess of 40 months. PMID:23721492

  15. The treatment of sublingual gland tumours.

    PubMed

    Sun, G; Yang, X; Tang, E; Wen, J; Lu, M; Hu, Q

    2010-09-01

    This study assessed the clinical and histological features and therapeutic efficacy of 25 cases of sublingual gland tumours from 1998 to 2008. There were 17 female patients and 8 male, the ratio of females to males was 2.1:1. The mean age was 48.6 years. 4 cases were benign tumours (16%). 21 cases were malignant sublingual gland tumours (84%) and of these, 18 were adenoid cystic carcinoma (86%). Adenoid cystic carcinoma was mainly of the histological type, and the other histological classifications included mucoepidermoid carcinoma, pleomorphic adenoma, myoepithelioma, oncocytoma and polymorphous low-grade adenocarcinoma. Sublingual gland tumours are rare and most are malignant. For malignant sublingual gland tumours, early diagnosis and aggressive surgical treatment, especially for tumours with nerve involvement, is the key to improving prognosis. Free radial forearm flap or pectoralis major myocutaneous flap are appropriate methods for mouth floor reconstruction. For benign sublingual gland tumours, the resection of tumour and sublingual gland is the preferred treatment.

  16. 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

  17. Melanoma-specific MHC-II expression represents a tumour-autonomous phenotype and predicts response to anti-PD-1/PD-L1 therapy

    PubMed Central

    Johnson, Douglas B.; Estrada, Monica V.; Salgado, Roberto; Sanchez, Violeta; Doxie, Deon B.; Opalenik, Susan R.; Vilgelm, Anna E.; Feld, Emily; Johnson, Adam S.; Greenplate, Allison R.; Sanders, Melinda E.; Lovly, Christine M.; Frederick, Dennie T.; Kelley, Mark C.; Richmond, Ann; Irish, Jonathan M.; Shyr, Yu; Sullivan, Ryan J.; Puzanov, Igor; Sosman, Jeffrey A.; Balko, Justin M.

    2016-01-01

    Anti-PD-1 therapy yields objective clinical responses in 30–40% of advanced melanoma patients. Since most patients do not respond, predictive biomarkers to guide treatment selection are needed. We hypothesize that MHC-I/II expression is required for tumour antigen presentation and may predict anti-PD-1 therapy response. In this study, across 60 melanoma cell lines, we find bimodal expression patterns of MHC-II, while MHC-I expression was ubiquitous. A unique subset of melanomas are capable of expressing MHC-II under basal or IFNγ-stimulated conditions. Using pathway analysis, we show that MHC-II(+) cell lines demonstrate signatures of ‘PD-1 signalling', ‘allograft rejection' and ‘T-cell receptor signalling', among others. In two independent cohorts of anti-PD-1-treated melanoma patients, MHC-II positivity on tumour cells is associated with therapeutic response, progression-free and overall survival, as well as CD4+ and CD8+ tumour infiltrate. MHC-II+ tumours can be identified by melanoma-specific immunohistochemistry using commercially available antibodies for HLA-DR to improve anti-PD-1 patient selection. PMID:26822383

  18. Neonatal tumours.

    PubMed

    Moore, S W

    2013-12-01

    Neonatal or perinatal tumours frequently relate to prenatal or developmental events and have a short exposure window which provides an opportunity to study tumours in a selective sensitive period of development. As a result, they display a number of host-specific features which include occasional spontaneous maturational changes with cells still responding to developmental influences. Neonatal tumours (NNT) are studied for a number of important reasons. Firstly, many of the benign tumours arising from soft tissue appear to result from disturbances in growth and development and some are associated with other congenital anomalies. Study of these aspects may open the door for investigation of genetic and epigenetic changes in genes controlling foetal development as well as environmental and drug effects during pregnancy. Secondly, the clinical behaviour of NNT differs from that of similar tumours occurring later in childhood. In addition, certain apparently malignant NNT can 'change course' in infancy leading to the maturation of apparently highly malignant tumours. Thirdly, NNT underline the genetic associations of most tumours but appear to differ in the effects of proto-oncogenes and other oncogenic factors. In this context, there are also connections between the foetal and neonatal period and some "adult" cancers. Fourthly, they appear to arise in a period in which minimal environmental interference has occurred, thus providing a unique potential window of opportunity to study the pathogenesis of tumour behaviour. This study will seek to review what is currently known in each of these areas of study as they apply to NNT. Further study of the provocative differences in tumour behaviour in neonates provides insights into the natural history of cancer in humans and promotes novel cancer therapies.

  19. CXCL1 mediates obesity-associated adipose stromal cell trafficking and function in the tumour microenvironment.

    PubMed

    Zhang, Tao; Tseng, Chieh; Zhang, Yan; Sirin, Olga; Corn, Paul G; Li-Ning-Tapia, Elsa M; Troncoso, Patricia; Davis, John; Pettaway, Curtis; Ward, John; Frazier, Marsha L; Logothetis, Christopher; Kolonin, Mikhail G

    2016-01-01

    White adipose tissue (WAT) overgrowth in obesity is linked with increased aggressiveness of certain cancers. Adipose stromal cells (ASCs) can become mobilized from WAT, recruited by tumours and promote cancer progression. Mechanisms underlying ASC trafficking are unclear. Here we demonstrate that chemokines CXCL1 and CXCL8 chemoattract ASC by signalling through their receptors, CXCR1 and CXCR2, in cell culture models. We further show that obese patients with prostate cancer have increased epithelial CXCL1 expression. Concomitantly, we observe that cells with ASC phenotype are mobilized and infiltrate tumours in obese patients. Using mouse models, we show that the CXCL1 chemokine gradient is required for the obesity-dependent tumour ASC recruitment, vascularization and tumour growth promotion. We demonstrate that αSMA expression in ASCs is induced by chemokine signalling and mediates the stimulatory effects of ASCs on endothelial cells. Our data suggest that ASC recruitment to tumours, driven by CXCL1 and CXCL8, promotes prostate cancer progression. PMID:27241286

  20. CXCL1 mediates obesity-associated adipose stromal cell trafficking and function in the tumour microenvironment

    PubMed Central

    Zhang, Tao; Tseng, Chieh; Zhang, Yan; Sirin, Olga; Corn, Paul G.; Li-Ning-Tapia, Elsa M.; Troncoso, Patricia; Davis, John; Pettaway, Curtis; Ward, John; Frazier, Marsha L.; Logothetis, Christopher; Kolonin, Mikhail G.

    2016-01-01

    White adipose tissue (WAT) overgrowth in obesity is linked with increased aggressiveness of certain cancers. Adipose stromal cells (ASCs) can become mobilized from WAT, recruited by tumours and promote cancer progression. Mechanisms underlying ASC trafficking are unclear. Here we demonstrate that chemokines CXCL1 and CXCL8 chemoattract ASC by signalling through their receptors, CXCR1 and CXCR2, in cell culture models. We further show that obese patients with prostate cancer have increased epithelial CXCL1 expression. Concomitantly, we observe that cells with ASC phenotype are mobilized and infiltrate tumours in obese patients. Using mouse models, we show that the CXCL1 chemokine gradient is required for the obesity-dependent tumour ASC recruitment, vascularization and tumour growth promotion. We demonstrate that αSMA expression in ASCs is induced by chemokine signalling and mediates the stimulatory effects of ASCs on endothelial cells. Our data suggest that ASC recruitment to tumours, driven by CXCL1 and CXCL8, promotes prostate cancer progression. PMID:27241286

  1. A standardized and reproducible protocol for serum-free monolayer culturing of primary paediatric brain tumours to be utilized for therapeutic assays.

    PubMed

    Sandén, Emma; Eberstål, Sofia; Visse, Edward; Siesjö, Peter; Darabi, Anna

    2015-01-01

    In vitro cultured brain tumour cells are indispensable tools for drug screening and therapeutic development. Serum-free culture conditions tentatively preserve the features of the original tumour, but commonly comprise neurosphere propagation, which is a technically challenging procedure. Here, we define a simple, non-expensive and reproducible serum-free cell culture protocol for establishment and propagation of primary paediatric brain tumour cultures as adherent monolayers. The success rates for establishment of primary cultures (including medulloblastomas, atypical rhabdoid tumour, ependymomas and astrocytomas) were 65% (11/17) and 78% (14/18) for sphere cultures and monolayers respectively. Monolayer culturing was particularly feasible for less aggressive tumour subsets, where neurosphere cultures could not be generated. We show by immunofluorescent labelling that monolayers display phenotypic similarities with corresponding sphere cultures and primary tumours, and secrete clinically relevant inflammatory factors, including PGE2, VEGF, IL-6, IL-8 and IL-15. Moreover, secretion of PGE2 was considerably reduced by treatment with the COX-2 inhibitor Valdecoxib, demonstrating the functional utility of our newly established monolayer for preclinical therapeutic assays. Our findings suggest that this culture method could increase the availability and comparability of clinically representative in vitro models of paediatric brain tumours, and encourages further molecular evaluation of serum-free monolayer cultures.

  2. A standardized and reproducible protocol for serum-free monolayer culturing of primary paediatric brain tumours to be utilized for therapeutic assays

    PubMed Central

    Sandén, Emma; Eberstål, Sofia; Visse, Edward; Siesjö, Peter; Darabi, Anna

    2015-01-01

    In vitro cultured brain tumour cells are indispensable tools for drug screening and therapeutic development. Serum-free culture conditions tentatively preserve the features of the original tumour, but commonly comprise neurosphere propagation, which is a technically challenging procedure. Here, we define a simple, non-expensive and reproducible serum-free cell culture protocol for establishment and propagation of primary paediatric brain tumour cultures as adherent monolayers. The success rates for establishment of primary cultures (including medulloblastomas, atypical rhabdoid tumour, ependymomas and astrocytomas) were 65% (11/17) and 78% (14/18) for sphere cultures and monolayers respectively. Monolayer culturing was particularly feasible for less aggressive tumour subsets, where neurosphere cultures could not be generated. We show by immunofluorescent labelling that monolayers display phenotypic similarities with corresponding sphere cultures and primary tumours, and secrete clinically relevant inflammatory factors, including PGE2, VEGF, IL-6, IL-8 and IL-15. Moreover, secretion of PGE2 was considerably reduced by treatment with the COX-2 inhibitor Valdecoxib, demonstrating the functional utility of our newly established monolayer for preclinical therapeutic assays. Our findings suggest that this culture method could increase the availability and comparability of clinically representative in vitro models of paediatric brain tumours, and encourages further molecular evaluation of serum-free monolayer cultures. PMID:26183281

  3. 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

  4. Primary Axillary Porocarcinoma: A Rare Cutaneous Tumour.

    PubMed

    Devi, Nalli R Sumitra; Valarmathi, K; Lilly, Mary; Satish, Selvi; Mishra, Nidhi

    2016-02-01

    Eccrine porocarcinoma, a rare cutaneous malignant tumour accounts for a fraction of sweat gland tumours. This tumour is found to originate from the intraepithelial parts of the sweat glands. It commonly involves the lower extremities in elderly patients and carries an aggressive behaviour. Cutaneous and visceral metastasis can occur and hence prompt treatment is mandatory. Surgical excision is the mainstay of treatment modality. We hereby present a case of eccrine porocarcinoma in a 50-year-old male in the right axillary region presenting as a verrucous lesion. PMID:27042472

  5. Characterization of twenty-five ovarian tumour cell lines that phenocopy primary tumours

    PubMed Central

    Ince, Tan A.; Sousa, Aurea D.; Jones, Michelle A.; Harrell, J. Chuck; Agoston, Elin S.; Krohn, Marit; Selfors, Laura M.; Liu, Wenbin; Chen, Ken; Yong, Mao; Buchwald, Peter; Wang, Bin; Hale, Katherine S.; Cohick, Evan; Sergent, Petra; Witt, Abigail; Kozhekbaeva, Zhanna; Gao, Sizhen; Agoston, Agoston T.; Merritt, Melissa A.; Foster, Rosemary; Rueda, Bo R.; Crum, Christopher P.; Brugge, Joan S.; Mills, Gordon B.

    2015-01-01

    Currently available human tumour cell line panels consist of a small number of lines in each lineage that generally fail to retain the phenotype of the original patient tumour. Here we develop a cell culture medium that enables us to routinely establish cell lines from diverse subtypes of human ovarian cancers with >95% efficiency. Importantly, the 25 new ovarian tumour cell lines described here retain the genomic landscape, histopathology and molecular features of the original tumours. Furthermore, the molecular profile and drug response of these cell lines correlate with distinct groups of primary tumours with different outcomes. Thus, tumour cell lines derived using this methodology represent a significantly improved platform to study human tumour pathophysiology and response to therapy. PMID:26080861

  6. Differences in phenotype and gene expression of prostate stromal cells from patients of varying ages and their influence on tumour formation by prostate epithelial cells

    PubMed Central

    Wang, Yong-Chuan; Yu, Sheng-Qiang; Wang, Xiao-Hai; Han, Bang-Min; Zhao, Fu-Jun; Zhu, Guang-Hui; Hong, Yan; Xia, Shu-Jie

    2011-01-01

    Prostate cancer (PCa) is an age-related disease, and the stromal microenvironment plays an important role in prostatic malignant progression. However, the differences in prostate stromal cells present in young and old tissue are still obscure. We established primary cultured stromal cells from normal prostatic peripheral zone (PZ) of donors of varying ages and found that cultured stromal cells from old donors (PZ-old) were more enlarged and polygonal than those from young donors (PZ-young). Furthermore, based on immunocytochemical and ultrastructural analysis, the components of stromal cells changed from a majority of fibroblasts to a mixture of fibroblasts and myofibroblasts with increasing donor age. Using a three-dimensional in vitro culture system, we found that PZ-old stromal cells could enhance the proliferation, migration and invasion of cocultured benign BPH-1 and PC-3 cells. Using an in vivo tissue recombination system, we also found that PZ-old stromal cells are more effective than PZ-young cells in promoting tumour formation by BPH-1 cells of high passage(>100) and PC-3 cells. To probe the possible mechanism of these effects, we performed cDNA microarray analysis and profiled 509 upregulated genes and 188 downregulated genes in PZ-old cells. Among the changed genes, we found genes coding for a subset of paracrine factors that are capable of influencing adjacent epithelial cells; these include hepatocyte growth factor (HGF), fibroblast growth factor 5 (FGF5), insulin-like growth factor 2 (IGF2), insulin-like growth factor-binding protein 4 (IGFBP4), IGFBP5 and matrix metallopeptidase 1 (MMP1). Changes in the expression of these genes were further confirmed by quantitative real-time polymerase chain reaction (PCR), Western blotting and enzyme-linked immunosorbent assays. Overall, our findings indicate that stromal cells from prostate PZ of old donors are more active than similar cells from young donors in promoting the malignant process of adjacent

  7. Chronic oxidative stress causes estrogen-independent aggressive phenotype, and epigenetic inactivation of estrogen receptor alpha in MCF-7 breast cancer cells.

    PubMed

    Mahalingaiah, Prathap Kumar S; Ponnusamy, Logeswari; Singh, Kamaleshwar P

    2015-08-01

    The role of chronic oxidative stress in the development and aggressive growth of estrogen receptor (ER)-positive breast cancer is well known; however, the mechanistic understanding is not clear. Estrogen-independent growth is one of the features of aggressive subtype of breast cancer. Therefore, the objective of this study was to evaluate the effect of oxidative stress on estrogen sensitivity and expression of nuclear estrogen receptors in ER-positive breast cancer cells. MCF-7 cells chronically exposed to hydrogen peroxide were used as a cell model in this study, and their growth in response to 17-β estradiol was evaluated by cell viability, cell cycle, and cell migration analysis. Results were further confirmed at molecular level by analysis of gene expressions at transcript and protein levels. Histone H3 modifications, expression of epigenetic regulatory genes, and the effect of DNA demethylation were also analyzed. Loss of growth in response to estrogen with a decrease in ERα expression was observed in MCF-7 cells adapted to chronic oxidative stress. Increases in mtTFA and NRF1 in these cells further suggested the role of mitochondria-dependent redox-sensitive growth signaling as an alternative pathway to estrogen-dependent growth. Changes in expression of epigenetic regulatory genes, levels of histone H3 modifications as well as significant restorations of both ERα expression and estrogen response by 5-Aza-2'-deoxycytidine further confirmed the epigenetic basis for estrogen-independent growth in these cells. In conclusion, results of this study suggest that chronic oxidative stress can convert estrogen-dependent nonaggressive breast cancer cells into estrogen-independent aggressive form potentially by epigenetic mechanism.

  8. Targeting the hypoxic fraction of tumours using hypoxia-activated prodrugs.

    PubMed

    Phillips, Roger M

    2016-03-01

    The presence of a microenvironment within most tumours containing regions of low oxygen tension or hypoxia has profound biological and therapeutic implications. Tumour hypoxia is known to promote the development of an aggressive phenotype, resistance to both chemotherapy and radiotherapy and is strongly associated with poor clinical outcome. Paradoxically, it is recognised as a high-priority target and one of the therapeutic strategies designed to eradicate hypoxic cells in tumours is a group of compounds known collectively as hypoxia-activated prodrugs (HAPs) or bioreductive drugs. These drugs are inactive prodrugs that require enzymatic activation (typically by 1 or 2 electron oxidoreductases) to generate cytotoxic species with selectivity for hypoxic cells being determined by (1) the ability of oxygen to either reverse or inhibit the activation process and (2) the presence of elevated expression of oxidoreductases in tumours. The concepts underpinning HAP development were established over 40 years ago and have been refined over the years to produce a new generation of HAPs that are under preclinical and clinical development. The purpose of this article is to describe current progress in the development of HAPs focusing on the mechanisms of action, preclinical properties and clinical progress of leading examples.

  9. Gastric calcifying fibrous tumour

    PubMed Central

    Attila, Tan; Chen, Dean; Gardiner, Geoffrey W; Ptak, Theadore W; Marcon, Norman E

    2006-01-01

    Intramucosal gastric tumours are most commonly found to be gastrointestinal stromal tumours or leiomyomas (smooth muscle tumours); however, a variety of other uncommon mesenchymal tumours can occur in the stomach wall. A rare benign calcifying fibrous tumour is reported and the endoscopic appearance, ultrasound findings and morphology are documented. A review of the literature found only two similar cases. PMID:16858502

  10. 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.

  11. Peripheral-type benzodiazepine receptor (PBR) in human breast cancer: correlation of breast cancer cell aggressive phenotype with PBR expression, nuclear localization, and PBR-mediated cell proliferation and nuclear transport of cholesterol.

    PubMed

    Hardwick, M; Fertikh, D; Culty, M; Li, H; Vidic, B; Papadopoulos, V

    1999-02-15

    nuclei was found to be 30% greater than into MCF-7 nuclei. High-affinity PBR drug ligands regulated the levels of cholesterol present in MDA-231 nuclei but not in MCF-7. In addition, the PBR-dependent MDA-231 cell proliferation was found to highly correlate (r = -0.99) with the PBR-mediated changes in nuclear membrane cholesterol levels. In conclusion, these data suggest that PBR expression, nuclear localization, and PBR-mediated cholesterol transport into the nucleus are involved in human breast cancer cell proliferation and aggressive phenotype expression, thus participating in the advancement of the disease.

  12. Imaging of testicular tumours.

    PubMed

    Owens, E J; Kabala, J; Goddard, P

    2004-01-01

    This article reviews the diagnosis, pathology and imaging of testicular tumours, predominantly germ cell tumours. It will discuss the imaging techniques used in their diagnosis, staging and surveillance.

  13. Cancer Cell Death-Inducing Radiotherapy: Impact on Local Tumour Control, Tumour Cell Proliferation and Induction of Systemic Anti-tumour Immunity.

    PubMed

    Frey, Benjamin; Derer, Anja; Scheithauer, Heike; Wunderlich, Roland; Fietkau, Rainer; Gaipl, Udo S

    2016-01-01

    Radiotherapy (RT) predominantly is aimed to induce DNA damage in tumour cells that results in reduction of their clonogenicity and finally in tumour cell death. Adaptation of RT with higher single doses has become necessary and led to a more detailed view on what kind of tumour cell death is induced and which immunological consequences result from it. RT is capable of rendering tumour cells immunogenic by modifying the tumour cell phenotype and the microenvironment. Danger signals are released as well as the senescence-associated secretory phenotype. This results in maturation of dendritic cells and priming of cytotoxic T cells as well as in activation of natural killer cells. However, RT on the other hand can also result in immune suppressive events including apoptosis induction and foster tumour cell proliferation. That's why RT is nowadays increasingly combined with selected immunotherapies. PMID:27558821

  14. Modelling evolutionary cell behaviour using neural networks: Application to tumour growth

    PubMed Central

    Anderson, A.R.A.

    2009-01-01

    In this paper we present a modelling framework for cellular evolution that is based on the notion that a cell’s behaviour is driven by interactions with other cells and its immediate environment. We equip each cell with a phenotype that determines its behaviour and implement a decision mechanism to allow evolution of this phenotype. This decision mechanism is modelled using feed-forward neural networks, which have been suggested as suitable models of cell signalling pathways. The environmental variables are presented as inputs to the network and result in a response that corresponds to the phenotype of the cell. The response of the network is determined by the network parameters, which are subject to mutations when the cells divide. This approach is versatile as there are no restrictions on what the input or output nodes represent, they can be chosen to represent any environmental variables and behaviours that are of importance to the cell population under consideration. This framework was implemented in an individual-based model of solid tumour growth in order to investigate the impact of the tissue oxygen concentration on the growth and evolutionary dynamics of the tumour. Our results show that the oxygen concentration affects the tumour at the morphological level, but more importantly has a direct impact on the evolutionary dynamics. When the supply of oxygen is limited we observe a faster divergence away from the initial genotype, a higher population diversity and faster evolution towards aggressive phenotypes. The implementation of this framework suggests that this approach is well suited for modelling systems where evolution plays an important role and where a changing environment exerts selection pressure on the evolving population. PMID:19026711

  15. Malignant Extra Renal Rhabdoid Tumour Presenting as Central Airway Obstruction

    PubMed Central

    Bal, Amanjit; Agarwal, Ritesh; Das, Ashim

    2014-01-01

    Rhabdoid tumours are one of the most aggressive childhood neoplasms associated with high mortality. The commonest age group affected is children less than five years of age. Rhabdoid tumour presenting as an endoluminal tracheal mass leading to central airway obstruction has not been previously reported. We describe the case of a 17-year-old male patient where malignant rhabdoid tumour masqueraded as bronchial asthma leading to a delayed diagnosis of upper airway obstruction by tracheal growth. Histopathological examination and immunohistochemistry confirmed the diagnosis of malignant rhabdoid tumour. PMID:25243090

  16. Ovatodiolide sensitizes aggressive breast cancer cells to doxorubicin, eliminates their cancer stem cell-like phenotype, and reduces doxorubicin-associated toxicity.

    PubMed

    Bamodu, Oluwaseun Adebayo; Huang, Wen-Chien; Tzeng, David T W; Wu, Alexander; Wang, Liang Shun; Yeh, Chi-Tai; Chao, Tsu-Yi

    2015-08-10

    Triple-negative breast cancer (TNBC) is chemotherapy-refractory and associated with poor clinical prognosis. Doxorubicin (Doxo), a class I anthracycline and first-line anticancer agent, effective against a wide spectrum of neoplasms including breast carcinoma, is associated with several cumulative dose-dependent adverse effects, including cardiomyopathy, typhilitis, and acute myelotoxicity. This study evaluated the usability of Ovatodiolide (Ova) in sensitizing TNBC cells to Doxo cytotoxicity, so as to reduce Doxo effective dose and consequently its adverse effects. TNBC cell lines MDA-MB-231 and HS578T were used. Pre-treatment of the TNBC cells with 10 µM Ova 24 h before Doxo administration increased the Doxo anticancer effect (IC50 1.4 µM) compared to simultaneous treatment with Doxo ( IC50 1.8 µM), or Doxo alone (IC50 9.2 µM). Intracellular accumulation of Doxo was lowest in Ova pre-treated cells at all Doxo concentrations, when compared with Doxo or simultaneously treated cells. In comparison to the Doxo-only group, cell cycle analysis of MDA-MB-231 cells treated concurrently with 2.5 µM Ova and 1.25 µM Doxo showed increased percentage of cells arrested at G0/G1; however, pre-treatment with the same concentration of Ova 24 h before Doxo showed greater tumor growth inhibition, with a 2.4-fold increased percentage of cells in G0/G1 arrest, greater Doxo-induced apoptosis, and significantly reduced intracellular Doxo accumulation. Additionally, Ova-sensitized TNBC cells also lost their cancer stem cell-like phenotype evidenced by significant dissolution, necrosis of formed mammospheres. Taken together, these findings indicate that Ova sensitizes TNBC cells to Doxo and potentiates doxorubicin-induced elimination of the TNBC cancer stem cell-like phenotype.

  17. Overexpression of Lon contributes to survival and aggressive phenotype of cancer cells through mitochondrial complex I-mediated generation of reactive oxygen species.

    PubMed

    Cheng, C-W; Kuo, C-Y; Fan, C-C; Fang, W-C; Jiang, S S; Lo, Y-K; Wang, T-Y; Kao, M-C; Lee, A Y-L

    2013-06-20

    Lon protease is a multifunction protein and operates in protein quality control and stress response pathways in mitochondria. Human Lon is upregulated under oxidative and hypoxic stresses that represent the stress phenotypes of cancer. However, little literature undertakes comprehensive and detailed investigations on the tumorigenic role of Lon. Overexpression of Lon promotes cell proliferation, apoptotic resistance to stresses, and transformation. Furthermore, Lon overexpression induces the production of mitochondrial reactive oxygen species (ROS) that result from Lon-mediated upregulation of NDUFS8, a mitochondrial Fe-S protein in complex I of electron transport chain. Increased level of mitochondrial ROS promotes cell proliferation, cell survival, cell migration, and epithelial-mesenchymal transition through mitogen-activated protein kinase (MAPK) and Ras-ERK activation. Overall, the present report for the first time demonstrates the role of Lon overexpression in tumorigenesis. Lon overexpression gives an apoptotic resistance to stresses and induces mitochondrial ROS production through Complex I as signaling molecules to activate Ras and MAPK signaling, giving the survival advantages and adaptation to cancer cells. Finally, in silico and immunohistochemistry analysis showed that Lon is overexpressed specifically in various types of cancer tissue including oral cancer.

  18. MicroRNA Regulation of Brain Tumour Initiating Cells in Central Nervous System Tumours

    PubMed Central

    Vijayakumar, Thusyanth; Bakhshinyan, David; Venugopal, Chitra; Singh, Sheila K.

    2015-01-01

    CNS tumours occur in both pediatric and adult patients and many of these tumours are associated with poor clinical outcome. Due to a paradigm shift in thinking for the last several years, these tumours are now considered to originate from a small population of stem-like cells within the bulk tumour tissue. These cells, termed as brain tumour initiating cells (BTICs), are perceived to be regulated by microRNAs at the posttranscriptional/translational levels. Proliferation, stemness, differentiation, invasion, angiogenesis, metastasis, apoptosis, and cell cycle constitute some of the significant processes modulated by microRNAs in cancer initiation and progression. Characterization and functional studies on oncogenic or tumour suppressive microRNAs are made possible because of developments in sequencing and microarray techniques. In the current review, we bring recent knowledge of the role of microRNAs in BTIC formation and therapy. Special attention is paid to two highly aggressive and well-characterized brain tumours: gliomas and medulloblastoma. As microRNA seems to be altered in the pathogenesis of many human diseases, “microRNA therapy” may now have potential to improve outcomes for brain tumour patients. In this rapidly evolving field, further understanding of miRNA biology and its contribution towards cancer can be mined for new therapeutic tools. PMID:26064134

  19. Circulating tumour cells and circulating free nucleic acid as prognostic and predictive biomarkers in colorectal cancer.

    PubMed

    Lim, S H; Becker, T M; Chua, W; Caixeiro, N J; Ng, W L; Kienzle, N; Tognela, A; Lumba, S; Rasko, J E J; de Souza, P; Spring, K J

    2014-04-28

    The detection of circulating tumour cells or circulating free tumour nucleic acids can potentially guide treatment and inform prognosis in colorectal cancer using minimally invasive "liquid biopsies". Current literature supports the notion that high circulating tumour cell counts or presence of tumour nucleic acid correlate with inferior clinical outcomes for patients, but they are not yet part of routine clinical care. Future research evolves around the examination of the molecular phenotype of circulating tumour cells. The key unanswered areas include differentiating between circulating tumour cell presence and their proliferative capacity and dormancy, identifying tumour heterogeneity and understanding the epithelial-mesenchymal transition.

  20. Proliferating tricholemmal tumour: clinicopathological aspects of a case.

    PubMed

    Khoja, A A; Yan, B; Lee, S J; Cheong, E C; Tan, K B

    2011-12-01

    We report the case of a 49-year-old man who presented with an enlarging mass over his occipital scalp. The clinical impression was either a squamous cell carcinoma or an unusual adnexal tumour. A wide excision was performed with skin grafting. Gross examination revealed a large exophytic tumour mass measuring 10 cm. Histopathological examination showed a circumscribed, well-differentiated squamoproliferative lesion with a lobulated architecture. Clear cell features, pilar-type keratinisation, microcalcifications and the presence of mucinous degeneration were noted. A diagnosis of proliferating tricholemmal tumour was made. This entity incorporates a spectrum of lesions, ranging from the mostly benign proliferating tricholemmal cyst to tumours having more atypical cellular and invasive features, the latter features correlating with an increased capacity for aggressive behaviour. Management-wise, such tumours require complete excision with follow-up. As the tumours are often large in size at presentation, reconstruction is required. PMID:22159947

  1. Collaboration of cancer-associated fibroblasts and tumour-associated macrophages for neuroblastoma development.

    PubMed

    Hashimoto, Okito; Yoshida, Makiko; Koma, Yu-Ichiro; Yanai, Tomoko; Hasegawa, Daiichiro; Kosaka, Yoshiyuki; Nishimura, Noriyuki; Yokozaki, Hiroshi

    2016-10-01

    Neuroblastoma is the most common extracranial solid tumour in children and is histologically classified by its Schwannian stromal cells. Although having fewer Schwannian stromal cells is generally associated with more aggressive phenotypes, the exact roles of other stromal cells (mainly macrophages and fibroblasts) are unclear. Here, we examined 41 cases of neuroblastoma using immunohistochemistry for the tumour-associated macrophage (TAM) markers CD68, CD163, and CD204, and a cancer-associated fibroblast (CAF) marker, alpha smooth muscle actin (αSMA). Each case was assigned to low/high groups on the basis of the number of TAMs or three groups on the basis of the αSMA-staining area for CAFs. Both the number of TAMs and the area of CAFs were significantly correlated with clinical stage, MYCN amplification, bone marrow metastasis, histological classification, histological type, and risk classification. Furthermore, TAM settled in the vicinity of the CAF area, suggesting their close interaction within the tumour microenvironment. We next determined the effects of conditioned medium of a neuroblastoma cell line (NBCM) on bone marrow-derived mesenchymal stem cells (BM-MSCs) and peripheral blood mononuclear cell (PBMC)-derived macrophages in vitro. The TAM markers CD163 and CD204 were significantly up-regulated in PBMC-derived macrophages treated with NBCM. The expression of αSMA by BM-MSCs was increased in NBCM-treated cells. Co-culturing with CAF-like BM-MSCs did not enhance the invasive ability but supported the proliferation of tumour cells, whereas tumour cells co-cultured with TAM-like macrophages had the opposite effect. Intriguingly, TAM-like macrophages enhanced not only the invasive abilities of tumour cells and BM-MSCs but also the proliferation of BM-MSCs. CXCL2 secreted from TAM-like macrophages plays an important role in tumour invasiveness. Taken together, these results indicate that PBMC-derived macrophages and BM-MSCs are recruited to a tumour site

  2. Collaboration of cancer-associated fibroblasts and tumour-associated macrophages for neuroblastoma development.

    PubMed

    Hashimoto, Okito; Yoshida, Makiko; Koma, Yu-Ichiro; Yanai, Tomoko; Hasegawa, Daiichiro; Kosaka, Yoshiyuki; Nishimura, Noriyuki; Yokozaki, Hiroshi

    2016-10-01

    Neuroblastoma is the most common extracranial solid tumour in children and is histologically classified by its Schwannian stromal cells. Although having fewer Schwannian stromal cells is generally associated with more aggressive phenotypes, the exact roles of other stromal cells (mainly macrophages and fibroblasts) are unclear. Here, we examined 41 cases of neuroblastoma using immunohistochemistry for the tumour-associated macrophage (TAM) markers CD68, CD163, and CD204, and a cancer-associated fibroblast (CAF) marker, alpha smooth muscle actin (αSMA). Each case was assigned to low/high groups on the basis of the number of TAMs or three groups on the basis of the αSMA-staining area for CAFs. Both the number of TAMs and the area of CAFs were significantly correlated with clinical stage, MYCN amplification, bone marrow metastasis, histological classification, histological type, and risk classification. Furthermore, TAM settled in the vicinity of the CAF area, suggesting their close interaction within the tumour microenvironment. We next determined the effects of conditioned medium of a neuroblastoma cell line (NBCM) on bone marrow-derived mesenchymal stem cells (BM-MSCs) and peripheral blood mononuclear cell (PBMC)-derived macrophages in vitro. The TAM markers CD163 and CD204 were significantly up-regulated in PBMC-derived macrophages treated with NBCM. The expression of αSMA by BM-MSCs was increased in NBCM-treated cells. Co-culturing with CAF-like BM-MSCs did not enhance the invasive ability but supported the proliferation of tumour cells, whereas tumour cells co-cultured with TAM-like macrophages had the opposite effect. Intriguingly, TAM-like macrophages enhanced not only the invasive abilities of tumour cells and BM-MSCs but also the proliferation of BM-MSCs. CXCL2 secreted from TAM-like macrophages plays an important role in tumour invasiveness. Taken together, these results indicate that PBMC-derived macrophages and BM-MSCs are recruited to a tumour site

  3. Tumour biology: Senescence in premalignant tumours

    NASA Astrophysics Data System (ADS)

    Collado, Manuel; Gil, Jesús; Efeyan, Alejo; Guerra, Carmen; Schuhmacher, Alberto J.; Barradas, Marta; Benguría, Alberto; Zaballos, Angel; Flores, Juana M.; Barbacid, Mariano; Beach, David; Serrano, Manuel

    2005-08-01

    Oncogene-induced senescence is a cellular response that may be crucial for protection against cancer development, but its investigation has so far been restricted to cultured cells that have been manipulated to overexpress an oncogene. Here we analyse tumours initiated by an endogenous oncogene, ras, and show that senescent cells exist in premalignant tumours but not in malignant ones. Senescence is therefore a defining feature of premalignant tumours that could prove valuable in the diagnosis and prognosis of cancer.

  4. 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…

  5. Predictive and prognostic value of metabolic tumour volume and total lesion glycolysis in solid tumours.

    PubMed

    Van de Wiele, Christophe; Kruse, Vibeke; Smeets, Peter; Sathekge, Mike; Maes, Alex

    2013-01-01

    Data available in patients suffering from squamous cell carcinoma of the head and neck, lung carcinoma, oesophageal carcinoma and gynaecological malignancies suggest that metabolic tumour volume and to a lesser extent total lesion glycolysis have the potential to become valuable in the imaging of human solid tumours as prognostic biomarkers for short- to intermediate-term survival outcomes, adding value to clinical staging, for assessment of response to treatment with neoadjuvant and concurrent chemotherapy, and for treatment optimization; for example, based on early treatment response assessment using changes in metabolic tumour volume over time, it might be possible to select patients who require a more aggressive treatment to improve their outcome. Prospective studies enrolling consecutive patients, adopting standardized protocols for FDG PET acquisition and processing, adjusting for potential confounders in the analysis (tumour size and origin) and determining the optimal methodology for determination of these novel markers are mandatory.

  6. Reduced expression of the polymeric immunoglobulin receptor in pancreatic and periampullary adenocarcinoma signifies tumour progression and poor prognosis.

    PubMed

    Fristedt, Richard; Elebro, Jacob; Gaber, Alexander; Jonsson, Liv; Heby, Margareta; Yudina, Yulyana; Nodin, Björn; Uhlén, Mathias; Eberhard, Jakob; Jirström, Karin

    2014-01-01

    The polymeric immunoglobulin receptor (pIgR) is a key component of the mucosal immune system that mediates epithelial transcytosis of immunoglobulins. High pIgR expression has been reported to correlate with a less aggressive tumour phenotype and an improved prognosis in several human cancer types. Here, we examined the expression and prognostic significance of pIgR in pancreatic and periampullary adenocarcinoma. The study cohort encompasses a consecutive series of 175 patients surgically treated with pancreaticoduodenectomy for pancreatic and periampullary adenocarcinoma in Malmö and Lund University Hospitals, Sweden, between 2001-2011. Tissue microarrays were constructed from primary tumours (n = 175) and paired lymph node metastases (n = 105). A multiplied score was calculated from the fraction and intensity of pIgR staining. Classification and regression tree analysis was used to select the prognostic cut-off. Unadjusted and adjusted hazard ratios (HR) for death and recurrence within 5 years were calculated. pIgR expression could be evaluated in 172/175 (98.3%) primary tumours and in 96/105 (91.4%) lymph node metastases. pIgR expression was significantly down-regulated in lymph node metastases as compared with primary tumours (p = 0.018). Low pIgR expression was significantly associated with poor differentiation grade (p < 0.001), perineural growth (p = 0.027), lymphatic invasion (p = 0.016), vascular invasion (p = 0.033) and infiltration of the peripancreatic fat (p = 0.039). In the entire cohort, low pIgR expression was significantly associated with an impaired 5-year survival (HR = 2.99, 95% confidence interval (CI) 1.71-5.25) and early recurrence (HR = 2.89, 95% CI 1.67-4.98). This association remained significant for survival after adjustment for conventional clinicopathological factors, tumour origin and adjuvant treatment (HR = 1.98, 95% CI 1.10-3.57). These results demonstrate, for the first time, that high tumour-specific pIgR expression signifies a

  7. Activation of blood coagulation in cancer: implications for tumour progression.

    PubMed

    Lima, Luize G; Monteiro, Robson Q

    2013-09-04

    Several studies have suggested a role for blood coagulation proteins in tumour progression. Herein, we discuss (1) the activation of the blood clotting cascade in the tumour microenvironment and its impact on primary tumour growth; (2) the intravascular activation of blood coagulation and its impact on tumour metastasis and cancer-associated thrombosis; and (3) antitumour therapies that target blood-coagulation-associated proteins. Expression levels of the clotting initiator protein TF (tissue factor) have been correlated with tumour cell aggressiveness. Simultaneous TF expression and PS (phosphatidylserine) exposure by tumour cells promote the extravascular activation of blood coagulation. The generation of blood coagulation enzymes in the tumour microenvironment may trigger the activation of PARs (protease-activated receptors). In particular, PAR1 and PAR2 have been associated with many aspects of tumour biology. The procoagulant activity of circulating tumour cells favours metastasis, whereas the release of TF-bearing MVs (microvesicles) into the circulation has been correlated with cancer-associated thrombosis. Given the role of coagulation proteins in tumour progression, it has been proposed that they could be targets for the development of new antitumour therapies.

  8. Activation of blood coagulation in cancer: implications for tumour progression

    PubMed Central

    Lima, Luize G.; Monteiro, Robson Q.

    2013-01-01

    Several studies have suggested a role for blood coagulation proteins in tumour progression. Herein, we discuss (1) the activation of the blood clotting cascade in the tumour microenvironment and its impact on primary tumour growth; (2) the intravascular activation of blood coagulation and its impact on tumour metastasis and cancer-associated thrombosis; and (3) antitumour therapies that target blood-coagulation-associated proteins. Expression levels of the clotting initiator protein TF (tissue factor) have been correlated with tumour cell aggressiveness. Simultaneous TF expression and PS (phosphatidylserine) exposure by tumour cells promote the extravascular activation of blood coagulation. The generation of blood coagulation enzymes in the tumour microenvironment may trigger the activation of PARs (protease-activated receptors). In particular, PAR1 and PAR2 have been associated with many aspects of tumour biology. The procoagulant activity of circulating tumour cells favours metastasis, whereas the release of TF-bearing MVs (microvesicles) into the circulation has been correlated with cancer-associated thrombosis. Given the role of coagulation proteins in tumour progression, it has been proposed that they could be targets for the development of new antitumour therapies. PMID:23889169

  9. A benign maxillary tumour with malignant features.

    PubMed

    Ricalde, Rosario R; Lim, Aimee Caroline E; Lopa, Ramon Antonio B; Carnate, Jose M

    2010-06-01

    Non-specific biopsy results such as chronic inflammation, hemorrhage, necrosis can be frustrating to the clinician. This is especially true if the patient presents with clinical features suggestive of an aggressive tumour. This is a review of the clinical features, diagnostic dilemmas and surgical management of a benign maxillary mass with malignant features - a disease called hematoma-like mass of the maxillary sinus (HLMMS). Our experience with five cases will also be cited. PMID:20502750

  10. Molecular crosstalk between tumour and brain parenchyma instructs histopathological features in glioblastoma.

    PubMed

    Bougnaud, Sébastien; Golebiewska, Anna; Oudin, Anaïs; Keunen, Olivier; Harter, Patrick N; Mäder, Lisa; Azuaje, Francisco; Fritah, Sabrina; Stieber, Daniel; Kaoma, Tony; Vallar, Laurent; Brons, Nicolaas H C; Daubon, Thomas; Miletic, Hrvoje; Sundstrøm, Terje; Herold-Mende, Christel; Mittelbronn, Michel; Bjerkvig, Rolf; Niclou, Simone P

    2016-05-31

    The histopathological and molecular heterogeneity of glioblastomas represents a major obstacle for effective therapies. Glioblastomas do not develop autonomously, but evolve in a unique environment that adapts to the growing tumour mass and contributes to the malignancy of these neoplasms. Here, we show that patient-derived glioblastoma xenografts generated in the mouse brain from organotypic spheroids reproducibly give rise to three different histological phenotypes: (i) a highly invasive phenotype with an apparent normal brain vasculature, (ii) a highly angiogenic phenotype displaying microvascular proliferation and necrosis and (iii) an intermediate phenotype combining features of invasion and vessel abnormalities. These phenotypic differences were visible during early phases of tumour development suggesting an early instructive role of tumour cells on the brain parenchyma. Conversely, we found that tumour-instructed stromal cells differentially influenced tumour cell proliferation and migration in vitro, indicating a reciprocal crosstalk between neoplastic and non-neoplastic cells. We did not detect any transdifferentiation of tumour cells into endothelial cells. Cell type-specific transcriptomic analysis of tumour and endothelial cells revealed a strong phenotype-specific molecular conversion between the two cell types, suggesting co-evolution of tumour and endothelial cells. Integrative bioinformatic analysis confirmed the reciprocal crosstalk between tumour and microenvironment and suggested a key role for TGFβ1 and extracellular matrix proteins as major interaction modules that shape glioblastoma progression. These data provide novel insight into tumour-host interactions and identify novel stroma-specific targets that may play a role in combinatorial treatment strategies against glioblastoma.

  11. Bronchial mucous gland tumours.

    PubMed

    Spencer, H

    1979-07-27

    Tumours arising in the bronchial mucous glands closely resemble tumours arising in the mixed salivary glands. Bronchial mucous gland tumours account for less than 0.5 per cent of all lung tumours. Twenty six tumours are reviewed and they have been divided into five types, (a) adenoidcystic carcinomas, (b) muco-epidermoid tumors, (c) mixed (pleomorphic) tumors, (d) cystadenomas and (f) oxyphilic adenoma. The clinical features, and postoperative course of the patients are reviewed. Adenocystic carcinomas, arising in the bronchus frequently involve the neighbouring trachea and spread mainly by direct infiltration. Most muco-epidermoid bronchial tumours were confined to young persons, and the only malignant muco-epidermoid tumour occurred in an elderly person. The prognosis in young persons is good provided the tumours are completely excised. The two mixed bronchial tumours resembled their salivary counterparts and one subsequently behaved as a carcinoma and metastasised. Bronchial cystadenomas all proved to be benign tumours but in two cases were associated with surface papillary proliferation. The only example of an oxyphil cell adenoma was discovered at post mortem examination. The histogenesis of the tumours is considered.

  12. Synchronous Appearance of Adenocarcinoma and Gastrointestinal Stromal Tumour (GIST) of the Stomach: A Case Report

    PubMed Central

    Pushparaj, Magesh; Masih, Dipti; Pulimood, Anna

    2016-01-01

    Adenocarcinoma is the most common histological type of gastric tumour, accounting for approximately 95% of all gastric carcinomas. Gastrointestinal stromal tumours (GISTs) are rare mesenchymal neoplasms of the digestive tract. Synchronous adenocarcinoma and gastrointestinal stromal tumour (GIST) occurring in the stomach is rare and very few cases have been reported in literature. Synchronous tumours in the stomach are rarely diagnosed preoperatively. A 63-year-old gentleman was diagnosed with a gastric adenocarcinoma on endoscopic biopsy and underwent surgery. Postoperative histopathologic examination revealed 2 synchronous tumours with both adenocarcinoma and GIST. The adenocarcinoma was determined to be the aggressive tumour based on histologic features. GIST was categorized as a very low risk of malignancy, based on its size and mitosis. The patient underwent chemotherapy for adenocarcinoma. He is under follow up and is currently disease free. Careful histopathologic evaluation is required to detect co-existing rare synchronous tumours. Presence of the second tumour may require additional procedures or protocols. PMID:27042477

  13. [Aggressive fibromatosis of the frontal sinus].

    PubMed

    Jensen, Søren Gade; Krogdahl, Annelise; Godballe, Christian

    2009-01-26

    Aggressive fibromatosis (AF) is a benign tumour with expansive and locally invasive growth. It is very rarely seen in the head and neck area. We present a 52-year-old female patient with AF localized to the left frontal sinus. The condition was initially mistaken for chronic sinusitis however computed tomography indicated tumour. A biopsy showed AF and the patient received surgical treatment. Symptoms, signs and treatment are discussed. It is concluded that AF in the sino-nasal tract is a rare, but potentially life threatening condition which might be mistaken for a simple sinusitis. PMID:19176167

  14. Circulating tumour cells: insights into tumour heterogeneity.

    PubMed

    Hayes, D F; Paoletti, C

    2013-08-01

    Tumour heterogeneity is a major barrier to cure breast cancer. It can exist between patients with different intrinsic subtypes of breast cancer or within an individual patient with breast cancer. In the latter case, heterogeneity has been observed between different metastatic sites, between metastatic sites and the original primary tumour, and even within a single tumour at either a metastatic or a primary site. Tumour heterogeneity is a function of two separate, although linked, processes. First, genetic instability is a hallmark of malignancy, and results in 'fixed' genetic changes that are almost certainly carried forward through progression of the cancer over time, with increasingly complex additional genetic changes in new metastases as they arise. The second type of heterogeneity is due to differential but 'plastic' expression of various genes important in the biology and response to various therapies. Together, these processes result in highly variable cancers with differential response, and resistance, to both targeted (e.g. endocrine or anti-human epithelial growth receptor type 2 (HER2) agents) and nontargeted therapies (e.g. chemotherapy). Ideally, tumour heterogeneity would be monitored over time, especially in relation to therapeutic strategies. However, biopsies of metastases require invasive and costly procedures, and biopsies of multiple metastases, or serially over time, are impractical. Circulating tumour cells (CTCs) represent a potential surrogate for tissue-based cancer and therefore might provide the opportunity to monitor serial changes in tumour biology. Recent advances have enabled accurate and reliable quantification and molecular characterization of CTCs with regard to a number of important biomarkers including oestrogen receptor alpha and HER2. Preliminary data have demonstrated that expression of these markers between CTCs in individual patients with metastatic breast cancer reflects the heterogeneity of the underlying tumours. Future

  15. Tumour progression and metastasis.

    PubMed

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2016-01-01

    The two biological mechanisms that determine types of malignancy are infiltration and metastasis, for which tumour microenvironment plays a key role in developing and establishing the morphology, growth and invasiveness of a malignancy. The microenvironment is formed by complex tissue containing the extracellular matrix, tumour and non-tumour cells, a signalling network of cytokines, chemokines, growth factors, and proteases that control autocrine and paracrine communication among individual cells, facilitating tumour progression. During the development of the primary tumour, the tumour stroma and continuous genetic changes within the cells makes it possible for them to migrate, having to count on a pre-metastatic niche receptor that allows the tumour's survival and distant growth. These niches are induced by factors produced by the primary tumour; if it is eradicated, the active niches become responsible for activating the latent disseminated cells. Due to the importance of these mechanisms, the strategies that develop tumour cells during tumour progression and the way in which the microenvironment influences the formation of metastasis are reviewed. It also suggests that the metastatic niche can be an ideal target for new treatments that make controlling metastasis possible.

  16. IMMUNOHISTOCHEMICAL AND BIOCHEMICAL ANALYSIS OF MAMMARY GLAND TUMOURS OF DIFFERENT AGE PATIENTS.

    PubMed

    Lykholat, T; Lykholat, O; Antonyuk, S

    2016-01-01

    Immunohistochemical and biochemical study of infiltrative ductal breast carcinoma and tissue adjacent to the tumour revealed a particular molecular profile and characteristics of the oxidant-antioxidant status neoplasms depending on the age of the patients and the presence of metastases in regional lymph nodes. Some causes of high aggressiveness and low hormone sensitivity of tumours in premenopausal women, as well as stability and high metastatic potential of tumours in postmenopausal women have been found. PMID:27266184

  17. The treatment of cranial germ cell tumours.

    PubMed

    Brandes, A A; Pasetto, L M; Monfardini, S

    2000-08-01

    Germ cell tumours of the central nervous system (CNS) include many subtypes whose response to treatment varies, even though the symptoms and radiological appearances are similar. Five-year survival rates are 96% for germinomas, 100% for mature teratomas, 67% for immature teratomas and 69% for immature teratomas mixed with germinomas; for beta-HCG secreting germinomas the rate is only 38%. Patients with choriocarcinoma, embryonal carcinoma, or yolk sac tumour have the lowest survival rates; patients with germinoma or mature teratoma have longer survival rates. Although a wider resection is associated with a higher rate of survival for patients with non-germinomatous germ cell (NGGC) tumours, to date an aggressive surgical approach has been advocated only for pineal region tumours, but not for hypothalamic/neurohypophyseal tumours. Beside the delayed injury induced by radiotherapy, the late injury induced by chemotherapy is becoming increasingly evident. Cisplatin is considered an indispensable drug, but it may cause renal damage, ototoxicity, peripheral neuropathy and sterility, while etoposide is associated with an excess frequency of second neoplasms. Taking into account all of the published literature, the following therapeutic options are suggested: in pure germinoma tumours (GT) radiotherapy alone will usually ensure adequate control of the disease, and the long-term sequelae may be limited by reducing the dose delivered, as was proposed for germ cell testicular tumours, to 30 Gy to limited fields plus 25-30 Gy to the spinal axis if there is disseminated disease. In cases of recurrence, which should be uncommon, patients may be rescued with both radiotherapy and chemotherapy. In NGGC tumours, the prognosis is more unfavourable and there is often dissemination to the spine at diagnosis; however, the tumour's high chemosensitivity suggests neoadjuvant treatment chemotherapy with cisplatin and etoposide for three cycles followed by consolidation radiotherapy with

  18. Tumour progression and metastasis

    PubMed Central

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2016-01-01

    The two biological mechanisms that determine types of malignancy are infiltration and metastasis, for which tumour microenvironment plays a key role in developing and establishing the morphology, growth and invasiveness of a malignancy. The microenvironment is formed by complex tissue containing the extracellular matrix, tumour and non-tumour cells, a signalling network of cytokines, chemokines, growth factors, and proteases that control autocrine and paracrine communication among individual cells, facilitating tumour progression. During the development of the primary tumour, the tumour stroma and continuous genetic changes within the cells makes it possible for them to migrate, having to count on a pre-metastatic niche receptor that allows the tumour’s survival and distant growth. These niches are induced by factors produced by the primary tumour; if it is eradicated, the active niches become responsible for activating the latent disseminated cells. Due to the importance of these mechanisms, the strategies that develop tumour cells during tumour progression and the way in which the microenvironment influences the formation of metastasis are reviewed. It also suggests that the metastatic niche can be an ideal target for new treatments that make controlling metastasis possible. PMID:26913068

  19. Immunophenotyping of diffuse large B-cell lymphoma (DLBCL) defines multiple sub-groups of germinal centre-like tumours displaying different survival characteristics.

    PubMed

    Anderson, John J; Fordham, Sarah; Overman, Lynne; Dignum, Helen; Wood, Katrina; Proctor, Stephen J; Crosier, Stephen; Angus, Brian; Culpin, Rachel E; Mainou-Fowler, Tryfonia

    2009-11-01

    Diffuse large B-cell lymphoma (DLBCL) forms a heterogeneous collection of aggressive non-Hodgkin's Lymphoma in which three principle classes of neoplasia have been defined according to gene expression and immunophenotyping studies. The present investigation sought to examine the immunophenotype of proposed subgroups and relate these to patient survival. A series of 155 DLBCL treated uniformly with anthracycline therapy in clinical trials, were stratified upon the basis of common biomarker expression with combination immunophenotype being related to patient overall survival. Stratification of tumours with respect to combined expression profiles of the three biological markers (CD10, Bcl-6 and MUM-1) revealed six groups showing significant differences in survival (p=0.014). The greatest difference resided between distinct populations of germinal centre (GC) cell tumours; the first being CD10-, Bcl-6+, MUM-1- and the second CD10+ Bcl-6+ MUM-1+ (p=0.002). The former group displayed median survival time of 143 months, the latter only 11 months. A third population of GC tumours (CD10+ Bcl-6+ and MUM-1-) also displayed a relative short median survival (32 months). Of the three groups presenting a non-GC or activated B cell (NGC/ABC) phenotype, only one (CD10-, Bcl-6+ and MUM-1+) presented short-term median survival (27 months) comparable with poor prognosis GC sub-populations. Within the remaining ABC tumour groups (CD10- Bcl-6- MUM-1- and CD10- Bcl-6- MUM-1+) patients presented intermediate median survival times of 54 and 58 months, respectively. Thus, the GC phenotype did not act as a universal indicator of good clinical prognosis, but rather multiple groups of GC tumours were associated with distinct overall survival profiles. Ultimately, the data allowed definition of a predictive algorithm defining three groups predicting poor, intermediate and good clinical prognosis. The first of these comprised two patient sub-populations with GC-like tumours together with one sub

  20. 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

  1. Carcinoid tumour of appendix in a child: a rare case at an uncommon site.

    PubMed

    Vani, B R; Thejaswini, M U; Kumar, B Deepak; Murthy, V Srinivasa; Geethamala, K

    2014-01-01

    Carcinoid tumours of the appendix are uncommon incidentally detected tumours during histopathological examination following appendicectomy for acute appendicitis. Even though considered rare in children, they are the most frequently encountered tumours of the gastrointestinal tract. To our knowledge, carcinoid tumour of appendix in childhood has not yet been reported from Indian Subcontinent. The clinical presentation is similar to acute appendicitis and the signs and symptoms of carcinoid syndrome have not been reported in children. The prognosis of carcinoid tumour of appendix is excellent in children as the tumour is generally small in size and less aggressive with no metastasis. Simple appendicectomy is curative in most of the patients and long term follow up is debatable. We present here a case of carcinoid tumour of the body of appendix, which is an uncommon location in a 6-year-old child.

  2. An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models

    PubMed Central

    2011-01-01

    Background Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression. Methods Primary cultures were established from human breast tumour and adjacent non-tumour tissue. Putative progenitor cell populations were isolated based on co-expression or concomitant absence of the epithelial and myoepithelial markers EPCAM and CALLA respectively. Results Significant reductions in cellular senescence were observed in tumour versus non-tumour cultures, accompanied by a stepwise increase in proliferation:senescence ratios. A novel correlation between tumour aggressiveness and an imbalance of putative progenitor subpopulations was also observed. Specifically, an increased double-negative (DN) to double-positive (DP) ratio distinguished aggressive tumours of high grade, estrogen receptor-negativity or HER2-positivity. The DN:DP ratio was also higher in malignant MDA-MB-231 cells relative to non-tumourogenic MCF-10A cells. Ultrastructural analysis of the DN subpopulation in an invasive tumour culture revealed enrichment in lipofuscin bodies, markers of ageing or senescent cells. Conclusions Our results suggest that an imbalance in tumour progenitor subpopulations imbalances the functional relationship between proliferation and senescence, creating a microenvironment favouring tumour progression. PMID:21521500

  3. Tuberculosis simulating brain tumour.

    PubMed

    Chaudhry, U R; Farooq, M; Rauf, F; Bhatti, S K

    2011-06-30

    The purpose of the study is to highlight the varied presentation of tuberculosis (TB) simulating a brain tumour. Headache and seizures are becoming frequent presenting complaints without any history of tuberculosis. The study comprises 1200 patients of both sexes with ages ranging from ten to sixty years. CT scan and MRI brain control with and without contrast medium were the investigations performed in these cases. In some patients Electroencephalography (EEG), cerebral angiography (DSA) and spectroscopy were also performed. The final diagnosis of tuberculosis was made on the basis of craniotomy, stereotactic and burr hole biopsies with histopathology in most of the cases. Forty per cent of the patients were followed up for eight months. They were put on anti-tuberculosis treatment with symptomatic and anti-epileptic drugs. The incidence was 544 and 757 per 100,000 in Africa and Indo Pakistan respectively. The male to female ratio was 1:1. Tuberculosis, especially with CNS involvement, is not only common in immunosuppressed patients in our setting, but TB has been and remains an important public health problem. TB may involve the CNS either as meningitis or as parenchymal granulomas or abscesses. Patients with brain TB usually present with fever, multiple cranial nerve involvement and occasional behavioural changes. CSF findings remain non specific in most cases. The most common sites are the cerebral hemisphere and basal ganglion in adults and the cerebellum in children. Tuberculosis has unique findings on brain CT and MRI. Cortical and subcortical locations are typical whereas the brain stem is a less common site. Tuberculosis lesions are usually solitary but multiple in 10% to 35% of cases. In spite of all these facts some cases of brain TB still need aggressive neurointervention to reach the final diagnosis of brain TB. Tuberculosis in the CNS may manifest in many different ways. So one should always include tuberculosis in the differential diagnosis in the

  4. Targeting the tumour microenvironment in ovarian cancer.

    PubMed

    Hansen, Jean M; Coleman, Robert L; Sood, Anil K

    2016-03-01

    The study of cancer initiation, growth, and metastasis has traditionally been focused on cancer cells, and the view that they proliferate due to uncontrolled growth signalling owing to genetic derangements. However, uncontrolled growth in tumours cannot be explained solely by aberrations in cancer cells themselves. To fully understand the biological behaviour of tumours, it is essential to understand the microenvironment in which cancer cells exist, and how they manipulate the surrounding stroma to promote the malignant phenotype. Ovarian cancer is the leading cause of death from gynaecologic cancer worldwide. The majority of patients will have objective responses to standard tumour debulking surgery and platinum-taxane doublet chemotherapy, but most will experience disease recurrence and chemotherapy resistance. As such, a great deal of effort has been put forth to develop therapies that target the tumour microenvironment in ovarian cancer. Herein, we review the key components of the tumour microenvironment as they pertain to this disease, outline targeting opportunities and supporting evidence thus far, and discuss resistance to therapy.

  5. Keratocystic Odontogenic Tumour with Extraosseal Spread: Evaluation of the Effect Carnoy's Solution.

    PubMed

    Levorová, Jitka; Machoň, Vladimír; Grill, Pavel; Hirjak, Dušan; Foltán, René

    2015-01-01

    Keratocystic odontogenic tumour is relatively rare benign tumour. It is characterized by its fast aggressive growth and high risk of recurrence. Treatment is always surgical: conservative (enucleation, marsupialization) or aggressive (enucleation followed by application of Carnoy's solution, cryotherapy; peripheral ostectomy or en block resection of the jaw). Authors analysed retrospectively 22 patients who fulfilled inclusion criteria, i.e. had odontogenic keratocystic tumour of mandible, wherein antero-posterior dimension was at least 30 mm, and the tumour penetrated into the surrounding soft tissues. All patients underwent tumour enucleation, in 11 patients Carnoy's solution was given into the bone cavity after enucleation. The recurrence rate in the evaluation at least 36 months after surgery was both patient groups the same: 45.4%. PMID:26654803

  6. Karyometry of nuclear phenotypes in Cutaneous Squamous Cell Cancer

    PubMed Central

    Bartels, Peter H.; Bartels, Hubert G.; Alberts, David S.; Yozwiak, M.; Prasad, Anil R.; Glazer, Evan; Krouse, Robert

    2014-01-01

    Objectives The objective of this study is to establish the karyometric characteristics of the two main nuclear phenotypes in cSCC lesions. Materials and Methods The clinical materials comprised 75 cases of cSCC, 38 with aggressive lesions and 37 with non-aggressive lesions. High-resolution images of 100 nuclei/case were recorded. The data were partitioned into four subgroups covering the range of lesion progression. Four discriminant functions were derived to distinguish aggressive from non-aggressive lesions. The most typical nuclei from the phenotype predominant in aggressive lesions, and from the phenotype predominant in non-aggressive lesions were separated out by thresholding on the discriminant function score axes. For these homogeneous sets of nuclei the karyometric features were computed. Results The nuclear populations in cSCC lesions are a very heterogeneous set. There are two axes of dispersion, along the line of lesion progression and between aggressive and non-aggressive lesions. The analysis faces the difficulty that lesions from both diagnostic categories contain nuclei of the same two phenotypes with the difference between categories consisting only of differences in proportion of the two phenotypes. Conclusions The nuclei of the aggressive phenotype I and non-aggressive phenotype II have substantially different chromatin patterns and can be distinguished with a better than 90 % correct recognition rate. PMID:22590813

  7. Uveal tumour resection

    PubMed Central

    Char, D.; Miller, T.; Crawford, J

    2001-01-01

    AIM—To review the ocular retention rates, visual results, and metastases in uveal tumours managed with eye wall resection techniques.
METHODS—This was a retrospective analysis of consecutive local uveal tumour resections performed by a single surgeon. All enucleation specimens were reviewed by one author. Both parametric and non-parametric analysis of data were performed.
RESULTS—138 eyes were scheduled for eye wall resection surgery. The mean age was 52 years (range 11-86 years). Tumours involved predominantly the iris in 14 cases, iris-ciliary body in 57, ciliary body alone in 18 patients, and in 49 cases the choroid was involved (ciliochoroidal, iris-ciliary body-choroid, or choroid). 125 eyes harboured melanomas; posterior tumours were more likely to have epithelioid cells (p<0.05). The mean follow up was 6 years. The mean clock hours in iris and iris-ciliary body tumours was 3.5. In tumours that involved the choroid the mean largest diameter was 12.9 mm and the mean thickness 8.5 mm. 105 of 138 (76%) eyes were retained. Histological assessment of surgical margins did not correlate evidence of tumour in enucleated eyes or metastatic disease. Surgical margins of more anterior tumours were more likely to be clear on histological evaluation (p<0.05). Approximately 53% of retained eyes had a final visual acuity of ⩾20/40; visual results were significantly better in more anteriorly located tumours (p<0.05). All retained iris tumour cases had ⩾20/40 final visual acuity. In tumours that involved the choroid nine of 31 retained eyes kept that level of visual acuity. Eight patients developed metastases; all metastatic events developed in patients with tumours that involved the choroid, and seven of eight were mixed cell melanomas.
CONCLUSIONS—76% of eyes were retained and 53% of these had a final visual acuity of ⩾20/40. Only 7% of uveal melanoma patients developed metastatic disease with a mean follow up of 6 years. Survival did not

  8. 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

  9. Methodological considerations when assessing restricted and repetitive behaviors and aggression

    PubMed Central

    Keefer, A.J.; Kalb, L.; Mazurek, M.O.; Kanne, S.M.; Freedman, B.; Vasa, R.A.

    2016-01-01

    Methodological issues impacting the relationship between aggression and restricted, repetitive, and stereotyped behaviors and interests (RRSBI) were examined in 2648 children and adolescents with autism spectrum disorders (ASD) using a multi-method, multi-informant analysis model to assess the effects of informant, assessment method, and aggression phenotype. Overall, a significant, but small relationship was found between RRSBI and aggression (p < .05). There was significant heterogeneity of estimates with large effect sizes observed when utilizing teacher report and a broad phenotype of aggression. Variance in estimates was attributed to differences in informant and assessment method with two times greater effect attributed to informant. Results suggest strategies to optimize future investigations of the relationship between RRSBI and aggression. Findings also provide the opportunity for the development of targeted interventions for aggression in youth with ASD. PMID:27239223

  10. 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

  11. 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

  12. Oncocytic tumours of the salivary gland, kidney, and thyroid: nuclear DNA patterns studied by flow cytometry.

    PubMed

    Rainwater, L M; Farrow, G M; Hay, I D; Lieber, M M

    1986-06-01

    Nuclear DNA ploidy studies were performed by flow cytometry on extracted nuclei from 12 oncocytic tumours of the salivary gland, 65 oncocytic tumours of the kidney, and 37 oncocytic tumours of the thyroid gland from the pathology archives of the Mayo Clinic. In order to provide an interesting clinical spectrum, three different classes of well-differentiated oncocytic tumours were selected for examination. Salivary gland oncocytic tumours were chosen for their generally benign behaviour. Oncocytic thyroid cancers exhibiting malignant potential because of local invasion, were thought to represent the opposite extreme of aggressiveness. Renal oncocytic tumours were known to demonstrate an intermediate degree of malignancy. All of the oncocytic salivary gland tumours showed a 'normal' DNA histogram and had a benign clinical course. For the oncocytic tumours of the kidney, 45% of DNA histograms were normal, 40% exhibited a significant increase in the DNA tetraploid/polyploid (4C) peak, and 15% showed a DNA aneuploid peak. Three patients with a DNA tetraploid pattern developed tumour metastasis and two have died from metastatic renal cancer. Among the oncocytic thyroid cancers, 27% were normal, 22% exhibited an increased DNA tetraploid peak, and 51% had a distinct DNA aneuploid peak. None of the thyroid tumour patients with a normal DNA pattern or with an increased DNA tetraploid peak died as a result of thyroid malignancy. In contrast, 58% of patients whose thyroid tumours showed a DNA aneuploid peak subsequently died from thyroid cancer.

  13. Guiding intracortical brain tumour cells to an extracortical cytotoxic hydrogel using aligned polymeric nanofibres

    NASA Astrophysics Data System (ADS)

    Jain, Anjana; Betancur, Martha; Patel, Gaurangkumar D.; Valmikinathan, Chandra M.; Mukhatyar, Vivek J.; Vakharia, Ajit; Pai, S. Balakrishna; Brahma, Barunashish; MacDonald, Tobey J.; Bellamkonda, Ravi V.

    2014-03-01

    Glioblastoma multiforme is an aggressive, invasive brain tumour with a poor survival rate. Available treatments are ineffective and some tumours remain inoperable because of their size or location. The tumours are known to invade and migrate along white matter tracts and blood vessels. Here, we exploit this characteristic of glioblastoma multiforme by engineering aligned polycaprolactone (PCL)-based nanofibres for tumour cells to invade and, hence, guide cells away from the primary tumour site to an extracortical location. This extracortial sink is a cyclopamine drug-conjugated, collagen-based hydrogel. When aligned PCL-nanofibre films in a PCL/polyurethane carrier conduit were inserted in the vicinity of an intracortical human U87MG glioblastoma xenograft, a significant number of human glioblastoma cells migrated along the aligned nanofibre films and underwent apoptosis in the extracortical hydrogel. Tumour volume in the brain was significantly lower following insertion of aligned nanofibre implants compared with the application of smooth fibres or no implants.

  14. Imaging the inside of a tumour: a review of radionuclide imaging and theranostics targeting intracellular epitopes.

    PubMed

    Cornelissen, Bart

    2014-04-01

    Molecular imaging of tumour tissue focusses mainly on extracellular epitopes such as tumour angiogenesis or signal transduction receptors expressed on the cell membrane. However, most biological processes that define tumour phenotype occur within the cell. In this mini-review, an overview is given of the various techniques to interrogate intracellular events using molecular imaging with radiolabelled compounds. Additionally, similar targeting techniques can be employed for radionuclide therapy using Auger electron emitters, and recent advances in Auger electron therapy are discussed.

  15. The neurobiology of aggression and violence.

    PubMed

    Rosell, Daniel R; Siever, Larry J

    2015-06-01

    Aggression and violence represent a significant public health concern and a clinical challenge for the mental healthcare provider. A great deal has been revealed regarding the neurobiology of violence and aggression, and an integration of this body of knowledge will ultimately serve to advance clinical diagnostics and therapeutic interventions. We will review here the latest findings regarding the neurobiology of aggression and violence. First, we will introduce the construct of aggression, with a focus on issues related to its heterogeneity, as well as the importance of refining the aggression phenotype in order to reduce pathophysiologic variability. Next we will examine the neuroanatomy of aggression and violence, focusing on regional volumes, functional studies, and interregional connectivity. Significant emphasis will be on the amygdala, as well as amygdala-frontal circuitry. Then we will turn our attention to the neurochemistry and molecular genetics of aggression and violence, examining the extensive findings on the serotonergic system, as well as the growing literature on the dopaminergic and vasopressinergic systems. We will also address the contribution of steroid hormones, namely, cortisol and testosterone. Finally, we will summarize these findings with a focus on reconciling inconsistencies and potential clinical implications; and, then we will suggest areas of focus for future directions in the field.

  16. Epstein-Barr virus as a marker of biological aggressiveness in breast cancer

    PubMed Central

    Mazouni, C; Fina, F; Romain, S; Ouafik, L; Bonnier, P; Brandone, J-M; Martin, P-M

    2011-01-01

    Purpose: Although a potential role of the Epstein-Barr virus (EBV) in the pathogenesis of breast cancer (BC) has been underlined, results remain conflicting. Particularly, the impact of EBV infection on biological markers of BC has received little investigation. Methods: In this study, we established the frequency of EBV-infected BC using real-time quantitative PCR (RT–PCR) in 196 BC specimens. Biological and pathological characteristics according to EBV status were evaluated. Results: EBV DNA was present in 65 of the 196 (33.2%) cases studied. EBV-positive BCs tended to be tumours with a more aggressive phenotype, more frequently oestrogen receptor negative (P=0.05) and with high histological grade (P=0.01). Overexpression of thymidine kinase activity was higher in EBV-infected BC (P=0.007). The presence of EBV was weakly associated with HER2 gene amplification (P=0.08). Conclusion: Our study provides evidence for EBV-associated BC undergoing distinct carcinogenic processes, with more aggressive features. PMID:21179039

  17. Tumours of the thymus

    PubMed Central

    Sellors, T. Holmes; Thackray, A. C.; Thomson, A. D.

    1967-01-01

    Eighty-eight cases of thymoma are discussed with the object of trying to co-ordinate the histological and clinical features. The pathological specimens were in all cases obtained at operation. The pathology classification introduced by Thomson and Thackray in 1957 has been found to correspond adequately with the clinical pattern. The most common groups of tumours are basically epithelial and can be separated into five or six subdivisions, each of which has a separate pattern of behaviour. Lymphoid and teratomatous tumours also occur, but there were only two examples in this series. Clinically, separation of patients who suffered from myasthenia (38) and those who did not (50) affords the first main grouping. The majority of patients who had myasthenia gravis had tumours classified as epidermoid (19) and lymphoepithelial (14), the former with a more malignant appearance and behaviour than the latter. Removal of the tumour with or without radiation gave considerable and sometimes complete relief from myasthenic symptoms. Non-myasthenic thymoma (50) was usually discovered as a result of pressure signs or in the course of routine radiography. Spindle or oval celled tumours followed a benign pattern whereas undifferentiated thymoma was in every sense malignant, as also were teratomatous growths. Granulomatous or Hodgkin-like thymomas were of special interest and had an unpredictable course, some patients surviving many years after what was regarded as inadequate treatment. The place of radiotherapy as a pre- or post-operative agent complementary to surgery is discussed. Images PMID:6033387

  18. Salivary gland tumours.

    PubMed

    Speight, P M; Barrett, A W

    2002-09-01

    Salivary gland tumours are a relatively rare and morphologically diverse group of lesions. Although most clinicians and pathologists will have encountered the more common benign neoplasms, few have experience of the full range of salivary cancers, which are best managed in specialist centres. This review considers some current areas of difficulty and controversy in the diagnosis and management of these neoplasms. The classification of these lesions is complex, encompassing nearly 40 different entities, but precise classification and terminology is essential for an accurate diagnosis and for the allocation of tumours to prognostic groups. For many salivary tumours diagnosis is straightforward but the wide range of morphological diversity between and within tumour types means that a diagnosis may not be possible on small incisional biopsies and careful consideration of the clinical and pathological features together is essential. Although tumour grading is important and helpful, it is not an independent prognostic indicator and must be considered in the context of stage. Large malignancies tend to have a poor prognosis regardless of grade and even high-grade neoplasms may do well when they are small. A helpful guide to management of salivary cancers is the '4 cm rule'.

  19. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas

    PubMed Central

    Xue, Wen; Zender, Lars; Miething, Cornelius; Dickins, Ross A.; Hernando, Eva; Krizhanovsky, Valery; Cordon-Cardo, Carlos; Lowe, Scott W.

    2015-01-01

    Although cancer arises from a combination of mutations in oncogenes and tumour suppressor genes, the extent to which tumour suppressor gene loss is required for maintaining established tumours is poorly understood. p53 is an important tumour suppressor that acts to restrict proliferation in response to DNA damage or deregulation of mitogenic oncogenes, by leading to the induction of various cell cycle checkpoints, apoptosis or cellular senescence1,2. Consequently, p53 mutations increase cell proliferation and survival, and in some settings promote genomic instability and resistance to certain chemotherapies3. To determine the consequences of reactivating the p53 pathway in tumours, we used RNA interference (RNAi) to conditionally regulate endogenous p53 expression in a mosaic mouse model of liver carcinoma4,5. We show that even brief reactivation of endogenous p53 in p53-deficient tumours can produce complete tumour regressions. The primary response to p53 was not apoptosis, but instead involved the induction of a cellular senescence program that was associated with differentiation and the upregulation of inflammatory cytokines. This program, although producing only cell cycle arrest in vitro, also triggered an innate immune response that targeted the tumour cells in vivo, thereby contributing to tumour clearance. Our study indicates that p53 loss can be required for the maintenance of aggressive carcinomas, and illustrates how the cellular senescence program can act together with the innate immune system to potently limit tumour growth. PMID:17251933

  20. Immunology of naturally transmissible tumours

    PubMed Central

    Siddle, Hannah V; Kaufman, Jim

    2015-01-01

    Naturally transmissible tumours can emerge when a tumour cell gains the ability to pass as an infectious allograft between individuals. The ability of these tumours to colonize a new host and to cross histocompatibility barriers contradicts our understanding of the vertebrate immune response to allografts. Two naturally occurring contagious cancers are currently active in the animal kingdom, canine transmissible venereal tumour (CTVT), which spreads among dogs, and devil facial tumour disease (DFTD), among Tasmanian devils. CTVT are generally not fatal as a tumour-specific host immune response controls or clears the tumours after transmission and a period of growth. In contrast, the growth of DFTD tumours is not controlled by the Tasmanian devil's immune system and the disease causes close to 100% mortality, severely impacting the devil population. To avoid the immune response of the host both DFTD and CTVT use a variety of immune escape strategies that have similarities to many single organism tumours, including MHC loss and the expression of immunosuppressive cytokines. However, both tumours appear to have a complex interaction with the immune system of their respective host, which has evolved over the relatively long life of these tumours. The Tasmanian devil is struggling to survive with the burden of this disease and it is only with an understanding of how DFTD passes between individuals that a vaccine might be developed. Further, an understanding of how these tumours achieve natural transmissibility should provide insights into general mechanisms of immune escape that emerge during tumour evolution. PMID:25187312

  1. An unusual case of a well-differentiated neuroendocrine tumour of the ileum with peritoneal carcinomatosis: a case report.

    PubMed

    Celotti, Andrea; Pulcini, Giuseppe; Schieppati, Mattia; Ministrini, Silvia; Berruti, Alfredo; Ronconi, Maurizio

    2015-01-01

    Neuroendocrine tumours (NETs) are a family of neoplasms that come from neuroendocrine cells and express neural markers, such as synaptophysin or chromogranin A.The current classifications of these tumours are presented by the WHO 2000 classification, based on histological parameters, and the WHO 2010 classification, based on the proliferative index, that divides the NETs into a neuroendocrine tumour of a low grade, neuroendocrine tumour of a intermediate grade and neuroendocrine carcinoma (NEC) of a high grade.We are reporting a very rare case of a G1 low-grade neuroendocrine tumour (NET) of the ileum with a peritoneal carcinomatosis.This case is challenging because the tumour expresses low proliferative index as G1 tumours, but it has an aggressive clinical behaviour such as node metastasis and peritoneal carcinomatosis.The peritoneal carcinomatosis is not actually considered by the current classifications of NETs, so it is difficult to predict the prognosis of this patient.

  2. Parallel evolution of tumour subclones mimics diversity between tumours.

    PubMed

    Martinez, Pierre; Birkbak, Nicolai Juul; Gerlinger, Marco; McGranahan, Nicholas; Burrell, Rebecca A; Rowan, Andrew J; Joshi, Tejal; Fisher, Rosalie; Larkin, James; Szallasi, Zoltan; Swanton, Charles

    2013-08-01

    Intratumour heterogeneity (ITH) may foster tumour adaptation and compromise the efficacy of personalized medicine approaches. The scale of heterogeneity within a tumour (intratumour heterogeneity) relative to genetic differences between tumours (intertumour heterogeneity) is unknown. To address this, we obtained 48 biopsies from eight stage III and IV clear cell renal cell carcinomas (ccRCCs) and used DNA copy-number analyses to compare biopsies from the same tumour with 440 single tumour biopsies from the Cancer Genome Atlas (TCGA). Unsupervised hierarchical clustering of TCGA and multi-region ccRCC samples revealed segregation of samples from the same tumour into unrelated clusters; 25% of multi-region samples appeared more similar to unrelated samples than to any other sample originating from the same tumour. We found that the majority of recurrent DNA copy number driver aberrations in single biopsies were not present ubiquitously in late-stage ccRCCs and were likely to represent subclonal events acquired during tumour progression. Such heterogeneous subclonal genetic alterations within individual tumours may impair the identification of robust ccRCC molecular subtypes classified by distinct copy number alterations and clinical outcomes. The co-existence of distinct subclonal copy number events in different regions of individual tumours reflects the diversification of individual ccRCCs through multiple evolutionary routes and may contribute to tumour sampling bias and impact upon tumour progression and clinical outcome.

  3. Parallel evolution of tumour subclones mimics diversity between tumours.

    PubMed

    Martinez, Pierre; Birkbak, Nicolai Juul; Gerlinger, Marco; McGranahan, Nicholas; Burrell, Rebecca A; Rowan, Andrew J; Joshi, Tejal; Fisher, Rosalie; Larkin, James; Szallasi, Zoltan; Swanton, Charles

    2013-08-01

    Intratumour heterogeneity (ITH) may foster tumour adaptation and compromise the efficacy of personalized medicine approaches. The scale of heterogeneity within a tumour (intratumour heterogeneity) relative to genetic differences between tumours (intertumour heterogeneity) is unknown. To address this, we obtained 48 biopsies from eight stage III and IV clear cell renal cell carcinomas (ccRCCs) and used DNA copy-number analyses to compare biopsies from the same tumour with 440 single tumour biopsies from the Cancer Genome Atlas (TCGA). Unsupervised hierarchical clustering of TCGA and multi-region ccRCC samples revealed segregation of samples from the same tumour into unrelated clusters; 25% of multi-region samples appeared more similar to unrelated samples than to any other sample originating from the same tumour. We found that the majority of recurrent DNA copy number driver aberrations in single biopsies were not present ubiquitously in late-stage ccRCCs and were likely to represent subclonal events acquired during tumour progression. Such heterogeneous subclonal genetic alterations within individual tumours may impair the identification of robust ccRCC molecular subtypes classified by distinct copy number alterations and clinical outcomes. The co-existence of distinct subclonal copy number events in different regions of individual tumours reflects the diversification of individual ccRCCs through multiple evolutionary routes and may contribute to tumour sampling bias and impact upon tumour progression and clinical outcome. PMID:23716380

  4. 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.

  5. Primary retroperitoneal tumours and cysts.

    PubMed

    Bors, G; Polyák, L; Frang, D

    1986-01-01

    The authors give a summarizing report on retroperitoneal tumours and cysts. They review the origin and classification of tumours and cysts, their diagnostic and differential diagnostic possibilities as well as the therapeutic measures. Finally, their own 3 cases are reported.

  6. Genetics of neuroendocrine and carcinoid tumours.

    PubMed

    Leotlela, P D; Jauch, A; Holtgreve-Grez, H; Thakker, R V

    2003-12-01

    Neuroendocrine tumours (NETs) originate in tissues that contain cells derived from the embryonic neural crest, neuroectoderm and endoderm. Thus, NETs occur at many sites in the body, although the majority occur within the gastro-entero-pancreatic axis and can be subdivided into those of foregut, midgut and hindgut origin. Amongst these, only those of midgut origin are generally argentaffin positive and secrete serotonin, and hence only these should be referred to as carcinoid tumours. NETs may occur as part of complex familial endocrine cancer syndromes, such as multiple endocrine neoplasia type 1 (MEN1), although the majority occur as non-familial (i.e. sporadic) isolated tumours. Molecular genetic studies have revealed that the development of NETs may involve different genes, each of which may be associated with several different abnormalities that include point mutations, gene deletions, DNA methylation, chromosomal losses and chromosomal gains. Indeed, the foregut, midgut and hindgut NETs develop via different molecular pathways. For example, foregut NETs have frequent deletions and mutations of the MEN1 gene, whereas midgut NETs have losses of chromosome 18, 11q and 16q and hindgut NETs express transforming growth factor-alpha and the epidermal growth factor receptor. Furthermore, in lung NETs, a loss of chromosome 3p is the most frequent change and p53 mutations and chromosomal loss of 5q21 are associated with more aggressive tumours and poor survival. In addition, methylation frequencies of retinoic acid receptor-beta, E-cadherin and RAS-associated domain family genes increase with the severity of lung NETs. Thus the development and progression of NETs is associated with specific genetic abnormalities that indicate the likely involvement of different molecular pathways.

  7. Desmoplastic small round cell tumour in a young woman with widespread metastasis and peritoneal caking.

    PubMed

    Monappa, Vidya; Bhat, Sudha S; Valiathan, Manna

    2013-12-01

    Desmoplastic Small Round Cell Tumour (DSRCT) is a rare, highly aggressive, mesenchymal tumour that arises from the peritoneal cavity. It is commonly seen in adolescent and young adult males and its occurrence in females is uncommon. We are reporting here a rare case of DSRCT in a young woman, which clinically masqueraded as an ovarian malignancy, with metastasis to liver, lung, spleen and peritoneum. The cytologic findings, Histomorphological and immunohistochemical features have been discussed, with a brief review of literature.

  8. Elastosis in malignant tumours.

    PubMed

    Isaacson, C; Greeff, H; Murray, J F; Posen, J; Schmaman, A

    1985-07-01

    Elastosis is common in infiltrating ductal and lobular carcinomas of the breast, occurring in approximately 90% of cases. It is also well described in some benign lesions of the breast and tumours of the salivary gland. Reports of venous elastosis in association with large-bowel carcinomas are rare. We describe elastosis in single cases of prostatic, gastric, bronchiolar-alveolar and cervical carcinoma.

  9. EGFR and microvessel density in canine malignant mammary tumours.

    PubMed

    Carvalho, Maria Isabel; Guimarães, Maria João; Pires, Isabel; Prada, Justina; Silva-Carvalho, Ricardo; Lopes, Carlos; Queiroga, Felisbina L

    2013-12-01

    The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor which has been shown to have an important role in human breast cancer. Its role appears to be associated with increased angiogenesis and metastasis. In order to clarify its role in canine mammary tumours (CMT), 61 malignant neoplasms were studied by using immunohistochemistry, comparing expression of EGFR, microvessel density (MVD) by CD31 immunolabelling and characteristics of tumour aggressiveness. High EGFR immunoexpression was statistically significantly associated with tumour size, tumour necrosis, mitotic grade, histological grade of malignancy and clinical stage. High CD31 immunoreactivity was statistically significantly associated with tubule formation, histological grade of malignancy and clinical stage. A positive correlation between EGFR and CD31 immunoexpression (r = 0.843; P < 0.001) was also observed. Results suggest that an over-expression of EGFR may contribute to increased angiogenesis and aggression in malignant CMT, presenting the possibility of using EGFR inhibitors in the context of metastatic disease treatment. PMID:24091029

  10. Phenotypic analysis of nylon-wool-adherent suppressor cells that inhibit the effector process of tumour cell lysis by lymphokine-activated killer cells in patients with advanced gastric carcinoma.

    PubMed

    Koyama, S; Fukao, K

    1994-01-01

    The causes of down-regulation of cytotoxic immune responses in cancer patients have not been fully evaluated. We previously demonstrated that T-cell-growth-factor-activated peripheral blood lymphocytes (PBL) with the surface phenotype CD8+ CD11b-, from patients with widespread metastasis of gastric carcinoma, inhibited the effector process of lymphokine-activated-killer(LAK)-cell-mediated cytolysis. In this study, we examined suppressor cell activity in freshly prepared PBL from 18 patients with advanced gastric carcinoma, and 10 normal healthy individuals. The suppressor cell activity was assayed by recording whether or not PBL inhibited directly the effector process of LAK cell cytotoxicity. Most of the PBL suspensions from cancer patients showed that they contained a population of cells that can directly inhibit the effector phase of tumor cell lysis of the cytotoxic cells. To analyze further the PBL responsible for the suppression, the cells were passed over a nylon-wool column. Nylon-wool-adherent cells significantly augmented the suppression, while the cells passing through abrogated the suppressive effect. Most nylon-wool-adherent cells from 10 normal healthy controls did not inhibit the cytotoxic reaction. To determine further the suppressor-effector population in nylon-wool-adherent cells, negative-selection studies using CD8-, CD4- or CD11b-coated magnetic beads, and positive-selection studies using CD8- or CD4-coated magnetic beads were performed. Finally the results suggest that the suppressor-effector cells comprise at least two different surface phenotypes: CD8+ T and CD8-CD11b+ cells. The possible role of CD4+ T cells and HLA-DR+ LeuM3+ macrophages as suppressor cells was ruled out in nylon-wool-adherent cells. CD8+ T and possibly CD8-CD11b+ cells apparently suppressed the efferent limb of the antitumor immunity. The selective immune suppression mediated by these cells may partly be concerned with escape mechanisms of gastric carcinoma from the host

  11. [Plasticity of the cellular phenotype].

    PubMed

    Chneiweiss, Hervé

    2011-01-01

    The tragical consequences of the Hiroshima and Nagasaki atomic bombs in 1945 were to lead to the discovery of hematopoietic stem cells and their phenotypic plasticity, in response to environmental factors. These concepts were much later extended to the founding cells of other tissues. In the following collection of articles, the mechanisms underlying this plasticity, at the frontiers of developmental biology and oncology, are illustrated in the case of various cell types of neural origin and of some tumours. PMID:21501574

  12. [Plasticity of the cellular phenotype].

    PubMed

    Chneiweiss, Hervé

    2011-01-01

    The tragical consequences of the Hiroshima and Nagasaki atomic bombs in 1945 were to lead to the discovery of hematopoietic stem cells and their phenotypic plasticity, in response to environmental factors. These concepts were much later extended to the founding cells of other tissues. In the following collection of articles, the mechanisms underlying this plasticity, at the frontiers of developmental biology and oncology, are illustrated in the case of various cell types of neural origin and of some tumours.

  13. Leukaemia cell of origin identified by chromatin landscape of bulk tumour cells

    PubMed Central

    George, Joshy; Uyar, Asli; Young, Kira; Kuffler, Lauren; Waldron-Francis, Kaiden; Marquez, Eladio; Ucar, Duygu; Trowbridge, Jennifer J.

    2016-01-01

    The precise identity of a tumour's cell of origin can influence disease prognosis and outcome. Methods to reliably define tumour cell of origin from primary, bulk tumour cell samples has been a challenge. Here we use a well-defined model of MLL-rearranged acute myeloid leukaemia (AML) to demonstrate that transforming haematopoietic stem cells (HSCs) and multipotent progenitors results in more aggressive AML than transforming committed progenitor cells. Transcriptome profiling reveals a gene expression signature broadly distinguishing stem cell-derived versus progenitor cell-derived AML, including genes involved in immune escape, extravasation and small GTPase signal transduction. However, whole-genome profiling of open chromatin reveals precise and robust biomarkers reflecting each cell of origin tested, from bulk AML tumour cell sampling. We find that bulk AML tumour cells exhibit distinct open chromatin loci that reflect the transformed cell of origin and suggest that open chromatin patterns may be leveraged as prognostic signatures in human AML. PMID:27397025

  14. Diagnosis and treatment of a rare sinonasal neuroendocrine tumour: adding to the evidence.

    PubMed

    Gudlavalleti, Aashrai; Dean, Ryan; Liu, Yuxin; Dhamoon, Amit S

    2016-01-01

    Sinonasal neuroendocrine tumours (NETs) are rare, aggressive neoplasms with a high recurrence potential. There are no robust protocols for the management of these tumours. An 81-year-old man presented with an incidental sinonasal mass visualised on CT scan of head. Over the next few weeks he developed new onset, progressively worsening headache, right eye ptosis and restricted extraocular movements. Imaging confirmed a rapidly enlarging tumour involving the right nasal cavity and the orbit. Biopsy showed a large cell neuroendocrine carcinoma of the right ethmoidal sinus. The patient was treated with concurrent cisplatin chemotherapy and radiation. Repeat imaging showed decrease in tumour volume. The patient continues to do well and follows up regularly with our oncology service. Current protocols comprising chemotherapy after radiation are based on limited studies. A regimen involving concurrent chemoradiation also appears to aid in tumour volume reduction. Additional studies are required to formulate robust clinical protocols for management of sinonasal NETs. PMID:27624450

  15. Current trends in the management of extra-abdominal desmoid tumours

    PubMed Central

    Papagelopoulos, Panayiotis J; Mavrogenis, Andreas F; Mitsiokapa, Evanthia A; Papaparaskeva, Kleo Th; Galanis, Evanthia C; Soucacos, Panayotis N

    2006-01-01

    Extra-abdominal desmoid tumours are slow-growing, histologically benign tumours of fibroblastic origin with variable biologic behaviour. They are locally aggressive and invasive to surrounding anatomic structures. Magnetic resonance imaging is the modality of choice for the diagnosis and the evaluation of the tumours. Current management of desmoids involves a multidisciplinary approach. Wide margin surgical resection remains the main treatment modality for local control of the tumour. Amputation should not be the initial treatment, and function-preserving procedures should be the primary treatment goal. Adjuvant radiation therapy is recommended both for primary and recurrent lesions. Chemotherapy may be used for recurrent or unresectable disease. Overall local recurrence rates vary and depend on patient's age, tumour location and margins at resection. PMID:16584569

  16. 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

  17. Vaccination with epigenetically treated mesothelioma cells induces immunisation and blocks tumour growth.

    PubMed

    Guillot, Flora; Boutin, Benoît; Blanquart, Christophe; Fonteneau, Jean-François; Robard, Myriam; Grégoire, Marc; Pouliquen, Daniel

    2011-07-26

    Malignant mesothelioma (MM) is an aggressive tumour associated with poor outcome in patients. Current treatments for MM are of limited efficacy. Our recent findings suggest that epigenetic drugs may induce both cytotoxicity and an immune response against MM cells. Thus, we used a mouse model of MM (AK7) to analyse how epigenetic drugs could modulate MM development in vivo. The treatment of tumour-bearing mice with an epigenetic drug already tested in clinical MM treatments (SAHA/Vorinostat) reduced the tumour mass and induced a moderate lymphocytic infiltration. However, the treatment did not stop tumour development. In order to show the potential effect of this epigenetic drug on tumour immunogenicity, in addition to cell cytotoxicity, we immunised mice either with AK7 cells pre-treated with SAHA, or with one of two cytotoxic drugs (curcumin or selenite), prior to transplantation of live AK7 cells. A specific immune response was observed only in mice immunised with AK7 cells pre-treated with the epigenetic drug (SAHA) and the tumour growth was arrested. An increase in the proportion of CD3+ CD8+ lymphocytes occurred in the peritoneal cavity. We also observed large conglomerates of immune cells in the omentum with clusters of CD8+ T cells, together with lymphocytes directed against residual AK7 cells in the interlobular connective tissue of the pancreas. Our data demonstrate that epigenetic drugs, such as SAHA, can stimulate tumour immunogenicity and improve the recognition of aggressive MM cells by the immune system in vivo. PMID:21619908

  18. Disentangling impulsiveness, aggressiveness and impulsive aggression: an empirical approach using self-report measures.

    PubMed

    García-Forero, Carlos; Gallardo-Pujol, David; Maydeu-Olivares, Alberto; Andrés-Pueyo, Antonio

    2009-06-30

    There is confusion in the literature concerning the concept of impulsive aggression. Based on previous research, we hypothesize that impulsivity and aggression may be related, though not as closely as to consider them the same construct. So, our aim was to provide empirical evidence of the relationship between the impulsivity and aggressiveness constructs when considered as traits. Two widely used questionnaires [Barratt's Impulsiveness Scale (BIS) and Aggression Questionnaire-Refined (AQ-R)] were administered to 768 healthy respondents. Product-moment and canonical correlations were then calculated. In addition, a principal components analysis was conducted to explore whether impulsive aggression can be defined phenotypically as the expression of a single trait. The common variance between impulsivity and aggressiveness was never higher than 42%. The principal components analysis reveals that one component is not enough to represent all the variables. In conclusion, our results show that impulsivity and aggressiveness are two separate, although related constructs. This is particularly important in view of the misconceptions in the literature.

  19. Laryngeal solitary fibrous tumour.

    PubMed

    Stomeo, Francesco; Padovani, Davide; Bozzo, Corrado; Pastore, Antonio

    2007-09-01

    Solitary fibrous tumours (SFT) are rare neoplasms, with an uncommon laryngeal involvement. Only five cases of laryngeal localization have been described in literature. The following is a case of a 75-year-old man with a supraglottic neoplasm of the larynx; after the biopsy immunohistochemical study demonstrated a strong positivity for vimentin, CD34 and Bcl-2. The neoplasm was consequently classified as a SFT. CO(2) laser surgery of the supraglottic larynx, with a wide excision of the neoplasm, was performed. Twenty-four months on, the patient is alive, well and free of disease. Surgical resection is the treatment of choice for laryngeal SFT, but tumour-free resection margins must be achieved to prevent the possibility of local recurrence. Endoscopic resection by means of the CO(2) laser must be accurately planned with MRI or CT imaging to confirm of this kind of surgery.

  20. The development of tumours under a ketogenic diet in association with the novel tumour marker TKTL1: A case series in general practice

    PubMed Central

    JANSEN, NATALIE; WALACH, HARALD

    2016-01-01

    Since the initial observations by Warburg in 1924, it has become clear in recent years that tumour cells require a high level of glucose to proliferate. Therefore, a ketogenic diet that provides the body with energy mainly through fat and proteins, but contains a reduced amount of carbohydrates, has become a dietary option for supporting tumour treatment and has exhibited promising results. In the present study, the first case series of such a treatment in general practice is presented, in which 78 patients with tumours were treated within a time window of 10 months. The patients were monitored regarding their levels of transketolase-like-1 (TKTL1), a novel tumour marker associated with aerobic glycolysis of tumour cells, and the patients' degree of adherence to a ketogenic diet. Tumour progression was documented according to oncologists' reports. Tumour status was correlated with TKTL1 expression (Kruskal-Wallis test, P<0.0001), indicating that more progressed and aggressive tumours may require a higher level of aerobic glycolysis. In palliative patients, a clear trend was observed in patients who adhered strictly to a ketogenic diet, with one patient experiencing a stagnation in tumour progression and others an improvement in their condition. The adoption of a ketogenic diet was also observed to affect the levels of TKTL1 in those patients. In conclusion, the results from the present case series in general practice suggest that it may be beneficial to advise tumour patients to adopt a ketogenic diet, and that those who adhere to it may have positive results from this type of diet. Thus, the use of a ketogenic diet as a complementary treatment to tumour therapy must be further studied in rigorously controlled trials. PMID:26870251

  1. Electrochemotherapy of Tumours

    PubMed Central

    Sersa, Gregor; Miklavcic, Damijan

    2008-01-01

    Electrochemotherapy is a combined use of certain chemotherapeutic drugs and electric pulses applied to the treated tumour nodule. Local application of electric pulses to the tumour increases drug delivery into cells, specifically at the site of electric pulse application. Drug uptake by delivery of electric pulses is increased for only those chemotherapeutic drugs whose transport through the plasma membrane is impeded. Among many drugs that have been tested so far, bleomycin and cisplatin found their way from preclinical testing to clinical use. Clinical data collected within a number of clinical studies indicate that approximately 80% of the treated cutaneous and subcutaneous tumour nodules of different malignancies are in an objective response, from these, approximately 70% in complete response after a single application of electrochemotherapy. Usually only one treatment is needed, however, electrochemotherapy can be repeated several times every few weeks with equal effectiveness each time. The treatment results in an effective eradication of the treated nodules, with a good cosmetic effect without tissue scarring. PMID:19229171

  2. Brain tumour stem cells: possibilities of new therapeutic strategies.

    PubMed

    Piccirillo, Sara G M; Vescovi, Angelo L

    2007-08-01

    Cancers are composed of heterogeneous cell populations, including highly proliferative immature precursors and differentiated cells, which may belong to different lineages. Recent advances in stem cell research have demonstrated the existence of tumour-initiating, cancer stem cells (CSCs) in non-solid and solid tumours. These cells are defined as CSCs because they show functional properties that resemble those of their normal counterpart to a significant extent. This concept applies to CSCs from brain tumours and, particularly, to glioblastoma stem-like cells, which self-renew under clonal conditions and differentiate into neuron- and glia-like cells, and into aberrant cells, with mixed neuronal/astroglia phenotypes. Notably, across serial transplantation into immunodeficient mice, glioblastoma stem-like cells are able to form secondary tumours which are a phenocopy of the human disease. A significant effort is underway to identify both CSC-specific markers and the molecular mechanism that underpin the tumorigenic potential of these cells, for this will have a critical impact on the understanding of the origin of malignant brain tumour and the discovery of new and more specific therapeutic approaches. Lately, the authors have shown that some of the bone morphogenetic proteins can reduce the tumorigenic ability of CSCs in GBMs. This suggests that mechanisms regulating the physiology of normal brain stem cells may be still in place in their cancerous siblings and that this may lead to the development of cures that selectively target the population CSCs found in the patients' tumour mass.

  3. Fibroblasts contribute to melanoma tumour growth and drug resistance

    PubMed Central

    Flach, Edward H.; Rebecca, Vito W.; Herlyn, Meenhard; Smalley, Keiran S. M.; Anderson, Alexander R. A.

    2011-01-01

    The role of tumour-stromal interactions in progression is generally well accepted but their role in initiation or treatment is less well understood. It is now generally agreed that rather than consisting solely of malignant cells, tumours consist of a complex dynamic mixture of cancer cells, host fibroblasts, endothelial cells, and immune cells that interact with each other and micro-environmental factors to drive tumour progression. We are particularly interested in stromal cells (for example fibroblasts) and stromal factors (for example fibronectin) as important players in tumour progression since they have also been implicated in drug resistance. Here we develop an integrated approach to understand the role of such stromal cells and factors in the growth and maintenance of tumours as well as their potential impact on treatment resistance, specifically in application to melanoma. Using a suite of experimental assays we show that melanoma cells can stimulate the recruitment of fibroblasts and activate them, resulting in melanoma cell growth by providing both structural (extra-cellular matrix proteins) and chemical support (growth factors). Motivated by these experimental results we construct a compartment model and use it to investigate the roles of both stromal activation and tumour aggressiveness in melanoma growth and progression. We utilise this model to investigate the role fibroblasts might play in melanoma treatment resistance and the clinically observed flare phenomena that is seen when a patient, who appears resistant to a targeted drug, is removed from that treatment. Our model makes the unexpected prediction that targeted therapies may actually hasten tumour progression once resistance has occurred. If confirmed experimentally, this provocative prediction may bring important new insights into how drug resistance could be managed clinically. PMID:22067046

  4. Limited neuropeptide Y precursor processing in unfavourable metastatic neuroblastoma tumours.

    PubMed

    Bjellerup, P; Theodorsson, E; Jörnvall, H; Kogner, P

    2000-07-01

    Neuropeptide Y (NPY) is found at high concentrations in neural crest-derived tumours and has been implicated as a regulatory peptide in tumour growth and differentiation. Neuroblastomas, ganglioneuromas and phaeochromocytomas with significant concentrations of NPY-like immunoreactivity were investigated for different molecular forms of NPY and for significance of proNPY processing. Gel-permeation chromatography identified intact NPY (1-36) in all tumours, whereas proNPY (69 amino acids) was detected only in control adrenal tissue and malignant neuroblastomas. Purification of NPY-like immunoreactivity in tumour extracts and structural characterization revealed that both NPY (1-36) and the truncated form NPY (3-36) was present. The degree of processing of proNPY to NPY in tumour tissue was lower in advanced neuroblastomas with regional or metastatic spread (stage 3 and 4) (n = 6), (41%, 12-100%, median, range), compared to the less aggressive stage 1, 2 and 4S tumours (n = 12), (93%; 69-100%), (P= 0.012). ProNPY processing of less than 50% was correlated with poor clinical outcome (P = 0.004). MYCN oncogene amplification was also correlated to a low degree of proNPY processing (P = 0.025). In summary, a low degree of proNPY processing was correlated to clinical advanced stage and poor outcome in neuroblastomas. ProNPY/NPY processing generated molecular forms of NPY with known differences in NPY-receptor selectivity, implicating a potential for in vivo modulation of NPY-like effects in tumour tissue.

  5. A cellular automaton model examining the effects of oxygen, hydrogen ions and lactate on early tumour growth.

    PubMed

    Al-Husari, Maymona; Murdoch, Craig; Webb, Steven D

    2014-10-01

    Some tumours are known to exhibit an extracellular pH that is more acidic than the intracellular, creating a 'reversed pH gradient' across the cell membrane and this has been shown to affect their invasive and metastatic potential. Tumour hypoxia also plays an important role in tumour development and has been directly linked to both tumour morphology and aggressiveness. In this paper, we present a hybrid mathematical model of intracellular pH regulation that examines the effect of oxygen and pH on tumour growth and morphology. In particular, we investigate the impact of pH regulatory mechanisms on the cellular pH gradient and tumour morphology. Analysis of the model shows that: low activity of the Na+/H+ exchanger or a high rate of anaerobic glycolysis can give rise to a "fingering" tumour morphology; and a high activity of the lactate/H+ symporter can result in a reversed transmembrane pH gradient across a large portion of the tumour mass. Also, the reversed pH gradient is spatially heterogeneous within the tumour, with a normal pH gradient observed within an intermediate growth layer within the spheroid. We also include a fractal dimension analysis of the simulated tumour contours, in which we compare the fractal dimensions of the simulated tumour surfaces with those found experimentally via photomicrographs.

  6. 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…

  7. Clinical features of gastroenteropancreatic tumours

    PubMed Central

    Czarnywojtek, Agata; Bączyk, Maciej; Ziemnicka, Katarzyna; Fischbach, Jakub; Wrotkowska, Elżbieta; Ruchała, Marek

    2015-01-01

    Gastroenteropancreatic (GEP) endocrine tumours (carcinoids and pancreatic islet cell tumours) are composed of multipotent neuroendocrine cells that exhibit a unique ability to produce, store, and secrete biologically active substances and cause distinct clinical syndromes. The classification of GEP tumours as functioning or non-functioning is based on the presence of symptoms that accompany these syndromes secondary to the secretion of hormones, neuropeptides and/or neurotransmitters (functioning tumours). Non-functioning tumours are considered to be neoplasms of neuroendocrine differentiation that are not associated with obvious symptoms attributed to the hypersecretion of metabolically active substances. However, a number of these tumours are either capable of producing low levels of such substances, which can be detected by immunohistochemistry but are insufficient to cause symptoms related to a clinical syndrome, or alternatively, they may secrete substances that are either metabolically inactive or inappropriately processed. In some cases, GEP tumours are not associated with the production of any hormone or neurotransmitter. Both functioning and non-functioning tumours can also produce symptoms due to mass effects compressing vital surrounding structures. Gastroenteropancreatic tumours are usually classified further according to the anatomic site of origin: foregut (including respiratory tract, thymus, stomach, duodenum, and pancreas), midgut (including small intestine, appendix, and right colon), and hindgut (including transverse colon, sigmoid, and rectum). Within these subgroups the biological and clinical characteristics of the tumours vary considerably, but this classification is still in use because a significant number of previous studies, mainly observational, have used it extensively. PMID:26516377

  8. 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.

  9. 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…

  10. 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…

  11. Molecular Classification of Breast Cancer Tumours from Patients Treated with Doxorubicin and Docetaxel

    PubMed Central

    2010-01-01

    It is known that four main molecular breast cancer subtypes have different prognoses and different responses to therapy. Luminal A tumours have a better prognosis and they tend to be sensitive to anti-estrogen drugs. Luminal B tumours have incomplete sensitivity to endocrine therapy. Her2 tumours, which have an aggressive natural history, are sensitive to trastuzumab. Finally, basal-like tumours might be eligible for chemotherapy. The aim of this study was to evaluate the chemosensitivity to docetaxel and doxorubicin of breast cancer subtypes. Patients with locally advanced breast cancer were randomized to receive 4 cycles of full dose doxorubicin (75 mg/m2) or docetaxel (100 mg/m2). After the fourth cycle, patients were submitted to surgery to ascertain pathological response. Treatment response was assessed according to Symmans classification. Among 130 samples analysed most ER positive tumours were luminal subtype. 41% of Her2 positive tumours assessed by immunohistochemistry and FISH were Her2 according to the gene expression profile. Luminal A and normal-like tumours have low expression of proliferation genes as well as ki67, whereas Her2 and basal-like tumours are highly proliferative. Both treatments have the same efficiency (20% of responses). However, basal tumours have the poorest outcome in the doxorubicin branch (0% of responses) while they are the most sensitive to docetaxel (50% of responses). Luminal and normal-like tumours have the poorest responses to both treatments. Finally, Her2 tumours had similar outcome in both branches (20% of responses). Genomic classification may assist the physician to choose a specific treatment based on the sub-type of tumour. This study provides the basis for building individualized neoadjuvant therapies for breast cancer.

  12. Modelling and Detecting Tumour Oxygenation Levels

    PubMed Central

    Skeldon, Anne C.; Chaffey, Gary; Lloyd, David J. B.; Mohan, Vineet; Bradley, David A.; Nisbet, Andrew

    2012-01-01

    Tumours that are low in oxygen (hypoxic) tend to be more aggressive and respond less well to treatment. Knowing the spatial distribution of oxygen within a tumour could therefore play an important role in treatment planning, enabling treatment to be targeted in such a way that higher doses of radiation are given to the more radioresistant tissue. Mapping the spatial distribution of oxygen in vivo is difficult. Radioactive tracers that are sensitive to different levels of oxygen are under development and in the early stages of clinical use. The concentration of these tracer chemicals can be detected via positron emission tomography resulting in a time dependent concentration profile known as a tissue activity curve (TAC). Pharmaco-kinetic models have then been used to deduce oxygen concentration from TACs. Some such models have included the fact that the spatial distribution of oxygen is often highly inhomogeneous and some have not. We show that the oxygen distribution has little impact on the form of a TAC; it is only the mean oxygen concentration that matters. This has significant consequences both in terms of the computational power needed, and in the amount of information that can be deduced from TACs. PMID:22761687

  13. Analysis of tumour cell composition in tumours composed of paired mixtures of mammary tumour cell lines.

    PubMed Central

    Miller, B. E.; Miller, F. R.; Wilburn, D. J.; Heppner, G. H.

    1987-01-01

    In order to quantitate the effects of tumour subpopulation interactions, we have devised a method to determine the subpopulation composition of tumours by using paired tumour cell lines able to grow in different selective media. Line 4T07 forms colonies in thioguanine but not in HAT and line 168 forms colonies in HAT but not in thioguanine. An independent technique of determining tumour cell content was used to validate this method: line 168 and 4T07 cells are distinguishable by flow cytometry after staining with propidium iodide for DNA content. Mixtures of cell suspensions prepared from each unmixed tumour, as well as from tumours arising from mixtures of these lines, were analysed by both the colony formation assay and by the DNA content assay. The colony formation assay yielded values in good agreement with the DNA content assay, but was considerably more sensitive in that it was able to quantitate minority subpopulations that constituted less than 10% of the tumour. Both methods revealed that in tumours arising from mixtures, the tumour cells were almost entirely line 4T07, even when the inoculum had contained a high proportion of 168 cells. Since line 168 cells are very tumorigenic per se, these results suggest that line 4T07 cells are capable of interfering with 168 proliferation in mixed tumours, either directly or through a host-mediated mechanism. PMID:3426919

  14. LET-painting increases tumour control probability in hypoxic tumours.

    PubMed

    Bassler, Niels; Toftegaard, Jakob; Lühr, Armin; Sørensen, Brita Singers; Scifoni, Emanuele; Krämer, Michael; Jäkel, Oliver; Mortensen, Lise Saksø; Overgaard, Jens; Petersen, Jørgen B

    2014-01-01

    LET-painting was suggested as a method to overcome tumour hypoxia. In vitro experiments have demonstrated a well-established relationship between the oxygen enhancement ratio (OER) and linear energy transfer (LET), where OER approaches unity for high-LET values. However, high-LET radiation also increases the risk for side effects in normal tissue. LET-painting attempts to restrict high-LET radiation to compartments that are found to be hypoxic, while applying lower LET radiation to normoxic tissues. Methods. Carbon-12 and oxygen-16 ion treatment plans with four fields and with homogeneous dose in the target volume, are applied on an oropharyngeal cancer case with an identified hypoxic entity within the tumour. The target dose is optimised to achieve a tumour control probability (TCP) of 95% when assuming a fully normoxic tissue. Using the same primary particle energy fluence needed for this plan, TCP is recalculated for three cases assuming hypoxia: first, redistributing LET to match the hypoxic structure (LET-painting). Second, plans are recalculated for varying hypoxic tumour volume in order to investigate the threshold volume where TCP can be established. Finally, a slight dose boost (5-20%) is additionally allowed in the hypoxic subvolume to assess its impact on TCP. Results. LET-painting with carbon-12 ions can only achieve tumour control for hypoxic subvolumes smaller than 0.5 cm(3). Using oxygen-16 ions, tumour control can be achieved for tumours with hypoxic subvolumes of up to 1 or 2 cm(3). Tumour control can be achieved for tumours with even larger hypoxic subvolumes, if a slight dose boost is allowed in combination with LET-painting. Conclusion. Our findings clearly indicate that a substantial increase in tumour control can be achieved when applying the LET-painting concept using oxygen-16 ions on hypoxic tumours, ideally with a slight dose boost.

  15. Miscellaneous tumour-like lesions of the ovary: cross-sectional imaging review

    PubMed Central

    Lalwani, N; Patel, S; Ha, K Y; Shanbhogue, A K; Nagar, A M; Chintapalli, K N; Prasad, S R

    2012-01-01

    Miscellaneous tumour-like ovarian lesions are histobiologically diverse, and are often mistaken for the more common ovarian cancers, leading to aggressive management. Knowledge of characteristic clinical, laboratory and imaging findings of these select non-neoplastic ovarian entities allows correct diagnoses and permits optimal management. PMID:22253351

  16. VEGF targets the tumour cell.

    PubMed

    Goel, Hira Lal; Mercurio, Arthur M

    2013-12-01

    The function of vascular endothelial growth factor (VEGF) in cancer is not limited to angiogenesis and vascular permeability. VEGF-mediated signalling occurs in tumour cells, and this signalling contributes to key aspects of tumorigenesis, including the function of cancer stem cells and tumour initiation. In addition to VEGF receptor tyrosine kinases, the neuropilins are crucial for mediating the effects of VEGF on tumour cells, primarily because of their ability to regulate the function and the trafficking of growth factor receptors and integrins. This has important implications for our understanding of tumour biology and for the development of more effective therapeutic approaches.

  17. Brain Tumours Simulating Psychiatric Disease

    PubMed Central

    Hobbs, G. E.

    1963-01-01

    Brain tumours may present with symptoms indistinguishable from psychiatric disease. The impression of most psychiatrists is that individuals suffering from brain tumour rarely appear among their patients. A priori reasoning based on evidence from neurological, neurosurgical and pathological sources suggests the contrary. The present study is a frequency analysis of cases of previously undiagnosed brain tumours admitted to either an open psychoneurotic ward or a mental hospital over a period of 15 years. The results support the impression held by psychiatrists that brain tumours are uncommon among psychiatric patients. PMID:13954870

  18. Quantitative Genomics of Aggressive Behavior in Drosophila melanogaster

    PubMed Central

    Edwards, Alexis C; Rollmann, Stephanie M; Morgan, Theodore J; Mackay, Trudy F. C

    2006-01-01

    Aggressive behavior is important for animal survival and reproduction, and excessive aggression is an enormous social and economic burden for human society. Although the role of biogenic amines in modulating aggressive behavior is well characterized, other genetic mechanisms affecting this complex behavior remain elusive. Here, we developed an assay to rapidly quantify aggressive behavior in Drosophila melanogaster, and generated replicate selection lines with divergent levels of aggression. The realized heritability of aggressive behavior was approximately 0.10, and the phenotypic response to selection specifically affected aggression. We used whole-genome expression analysis to identify 1,539 probe sets with different expression levels between the selection lines when pooled across replicates, at a false discovery rate of 0.001. We quantified the aggressive behavior of 19 mutations in candidate genes that were generated in a common co-isogenic background, and identified 15 novel genes affecting aggressive behavior. Expression profiling of genetically divergent lines is an effective strategy for identifying genes affecting complex traits. PMID:17044737

  19. Malignant testicular tumours

    PubMed Central

    Vecchio, Pierre Del; Tawil, Elie; Béland, Gilles

    1974-01-01

    A series of 71 patients with malignant testicular tumours treated primarily by orchiectomy and irradiation is reviewed with respect to pathological and clinical features and modes of treatment. The three-year crude survival rate in 36 patients with seminoma was 86% and in 24 patients with carcinoma it was 41.7%. There were no survivors among patients with choriocarcinoma. Our results are comparable with those of other series. A prospective study is proposed of the value of irradiation and subsequent limited lymph node dissection following orchiectomy in cases of carcinoma of the testis. PMID:4855670

  20. Copper depletion inhibits CoCl2-induced aggressive phenotype of MCF-7 cells via downregulation of HIF-1 and inhibition of Snail/Twist-mediated epithelial-mesenchymal transition.

    PubMed

    Li, Shun; Zhang, Jing; Yang, Hong; Wu, Chunhui; Dang, Xitong; Liu, Yiyao

    2015-01-01

    Copper, a strictly regulated trace element, is essential for many physiological processes including angiogenesis. Dysregulated angiogenesis has been associated with increased copper in tumors, and thus copper chelators have been used to inhibit tumor angiogenesis. However, it remains unclear whether copper has any effect on epithelial-mesenchymal transition (EMT). Using CoCl2-induced EMT of human breast carcinoma MCF-7 cells, we found that TEPA, a copper chelator, inhibited EMT-like cell morphology and cytoskeleton arrangement triggered by CoCl2; decreased the expression of vimentin and fibronectin, markers typical of EMT; inhibited HIF-1 activation and HIF1-α accumulation in nuclear; and down-regulated the expression of hypoxia-associated transcription factors, Snail and Twist1. Moreover, knockdown copper transport protein, Ctr1, also inhibited CoCl2-induced EMT and reversed the mesenchymal phenotype. In EMT6 xenograft mouse models, TEPA administration inhibited the tumor growth and increased mice survival. Immunohistochemical analysis of the xenograft further demonstrated that TEPA administration significantly inhibited tumor angiogenesis, down-regulated hypoxia-induced transcription factors, Snail and Twist1, leading to decreased transactivation of EMT-associated marker genes, vimentin and fibronectin. These results indicate that TEPA inhibits CoCl2-induced EMT most likely via HIF1-α-Snail/Twist signaling pathway, and copper depletion may be exploited as a therapeutic for breast cancer. PMID:26174737

  1. Copper depletion inhibits CoCl2-induced aggressive phenotype of MCF-7 cells via downregulation of HIF-1 and inhibition of Snail/Twist-mediated epithelial-mesenchymal transition.

    PubMed

    Li, Shun; Zhang, Jing; Yang, Hong; Wu, Chunhui; Dang, Xitong; Liu, Yiyao

    2015-07-15

    Copper, a strictly regulated trace element, is essential for many physiological processes including angiogenesis. Dysregulated angiogenesis has been associated with increased copper in tumors, and thus copper chelators have been used to inhibit tumor angiogenesis. However, it remains unclear whether copper has any effect on epithelial-mesenchymal transition (EMT). Using CoCl2-induced EMT of human breast carcinoma MCF-7 cells, we found that TEPA, a copper chelator, inhibited EMT-like cell morphology and cytoskeleton arrangement triggered by CoCl2; decreased the expression of vimentin and fibronectin, markers typical of EMT; inhibited HIF-1 activation and HIF1-α accumulation in nuclear; and down-regulated the expression of hypoxia-associated transcription factors, Snail and Twist1. Moreover, knockdown copper transport protein, Ctr1, also inhibited CoCl2-induced EMT and reversed the mesenchymal phenotype. In EMT6 xenograft mouse models, TEPA administration inhibited the tumor growth and increased mice survival. Immunohistochemical analysis of the xenograft further demonstrated that TEPA administration significantly inhibited tumor angiogenesis, down-regulated hypoxia-induced transcription factors, Snail and Twist1, leading to decreased transactivation of EMT-associated marker genes, vimentin and fibronectin. These results indicate that TEPA inhibits CoCl2-induced EMT most likely via HIF1-α-Snail/Twist signaling pathway, and copper depletion may be exploited as a therapeutic for breast cancer.

  2. Use of haloperidol and risperidone in highly aggressive Swiss Webster mice by applying the model of spontaneous aggression (MSA).

    PubMed

    Fragoso, Viviane Muniz da Silva; Hoppe, Luanda Yanaan; de Araújo-Jorge, Tânia Cremonini; de Azevedo, Marcos José; Campos, Jerônimo Diego de Souza; Cortez, Célia Martins; de Oliveira, Gabriel Melo

    2016-03-15

    Aggression is defined as the act in which an individual intentionally harms or injures another of their own species. Antipsychotics are a form of treatment used in psychiatric routine. They have been used for decades in treatment of patients with aggressive behavior. Haloperidol and risperidone promote the control of psychiatric symptoms, through their respective mechanisms of action. Experimental models are obtained by behavioral, genetic, and pharmacological manipulations, and use a reduced number of animals. In this context, we applied the model of spontaneous aggression (MSA), originating the presence of highly aggressive mice (AgR) when reassembled in adulthood. We administered haloperidol and risperidone in escalating doses, for ten consecutive days. Using positive and negative control groups, we evaluated the effectiveness of these drugs and the reversal of the aggressive behavior, performing the tail suspension test (TST) and open field test (OFT) on 10th day of treatment and 10 days after its discontinuation. The results showed that both antipsychotic drugs were effective in AgR and reversed the aggressive phenotype, reducing the number of attacks by AgR and the extent of lesions in the subordinate mice (AgD) exposed to the pattern of aggressive behavior (PAB) of the aggressors. This conclusion is based on the reduction in the animals' motor and exploratory activity, and on the reversal of patterns of aggressive behavior. The association between the MSA and experiments with other therapeutic protocols and different antipsychotics can be an important methodology in the study of aggressive behavior in psychiatric patients.

  3. Primary osseous tumours of the elbow: 60 years of registry experience

    PubMed Central

    Halai, Mansur; Gupta, Sanjay; Wallace, David; Rymaszewski, Lech; Mahendra, Ashish

    2015-01-01

    Background We present the largest series of surgically treated primary bone tumours of the elbow in the English literature (75 cases). We sought to identify characteristics specific to these lesions and recommend an investigatory protocol. Methods The national registry and case notes were reviewed between 1954-2014. Tumours were classified according to Enneking's spectrum. Results There were no benign latent cases in this series as these were managed locally. All patients presented with persistent rest pain, with or without swelling. The distal humerus, in contrast to the proximal radius and ulna, was responsible for the majority and the more aggressive cases. Misdiagnosis was evident in 13% of cases; most of which were attributed to simple bone cysts. All patients that were referred required surgical intervention to either establish the diagnosis or for treatment. Benign tumours had a 19% recurrence rate, with giant cell tumour the most aggressive. Malignant tumours carried 39% local recurrence rate and a 5-year mortality of 61%. Conclusions The suspicion of a tumour should be raised in the patient with unremitting, unexplained, non-mechanical bony elbow pain. These echo the NICE recommendations and we recommend prompt specialist referral. With high rates of local recurrence, we recommend close postoperative monitoring. PMID:27582988

  4. Brain monoamine oxidase A activity predicts trait aggression.

    PubMed

    Alia-Klein, Nelly; Goldstein, Rita Z; Kriplani, Aarti; Logan, Jean; Tomasi, Dardo; Williams, Benjamin; Telang, Frank; Shumay, Elena; Biegon, Anat; Craig, Ian W; Henn, Fritz; Wang, Gene-Jack; Volkow, Nora D; Fowler, Joanna S

    2008-05-01

    The genetic deletion of monoamine oxidase A (MAO A), an enzyme that breaks down the monoamine neurotransmitters norepinephrine, serotonin, and dopamine, produces aggressive phenotypes across species. Therefore, a common polymorphism in the MAO A gene (MAOA, Mendelian Inheritance in Men database number 309850, referred to as high or low based on transcription in non-neuronal cells) has been investigated in a number of externalizing behavioral and clinical phenotypes. These studies provide evidence linking the low MAOA genotype and violent behavior but only through interaction with severe environmental stressors during childhood. Here, we hypothesized that in healthy adult males the gene product of MAO A in the brain, rather than the gene per se, would be associated with regulating the concentration of brain amines involved in trait aggression. Brain MAO A activity was measured in vivo in healthy nonsmoking men with positron emission tomography using a radioligand specific for MAO A (clorgyline labeled with carbon 11). Trait aggression was measured with the multidimensional personality questionnaire (MPQ). Here we report for the first time that brain MAO A correlates inversely with the MPQ trait measure of aggression (but not with other personality traits) such that the lower the MAO A activity in cortical and subcortical brain regions, the higher the self-reported aggression (in both MAOA genotype groups) contributing to more than one-third of the variability. Because trait aggression is a measure used to predict antisocial behavior, these results underscore the relevance of MAO A as a neurochemical substrate of aberrant aggression. PMID:18463263

  5. 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…

  6. Adapting radiotherapy to hypoxic tumours

    NASA Astrophysics Data System (ADS)

    Malinen, Eirik; Søvik, Åste; Hristov, Dimitre; Bruland, Øyvind S.; Rune Olsen, Dag

    2006-10-01

    In the current work, the concepts of biologically adapted radiotherapy of hypoxic tumours in a framework encompassing functional tumour imaging, tumour control predictions, inverse treatment planning and intensity modulated radiotherapy (IMRT) were presented. Dynamic contrast enhanced magnetic resonance imaging (DCEMRI) of a spontaneous sarcoma in the nasal region of a dog was employed. The tracer concentration in the tumour was assumed related to the oxygen tension and compared to Eppendorf histograph measurements. Based on the pO2-related images derived from the MR analysis, the tumour was divided into four compartments by a segmentation procedure. DICOM structure sets for IMRT planning could be derived thereof. In order to display the possible advantages of non-uniform tumour doses, dose redistribution among the four tumour compartments was introduced. The dose redistribution was constrained by keeping the average dose to the tumour equal to a conventional target dose. The compartmental doses yielding optimum tumour control probability (TCP) were used as input in an inverse planning system, where the planning basis was the pO2-related tumour images from the MR analysis. Uniform (conventional) and non-uniform IMRT plans were scored both physically and biologically. The consequences of random and systematic errors in the compartmental images were evaluated. The normalized frequency distributions of the tracer concentration and the pO2 Eppendorf measurements were not significantly different. 28% of the tumour had, according to the MR analysis, pO2 values of less than 5 mm Hg. The optimum TCP following a non-uniform dose prescription was about four times higher than that following a uniform dose prescription. The non-uniform IMRT dose distribution resulting from the inverse planning gave a three times higher TCP than that of the uniform distribution. The TCP and the dose-based plan quality depended on IMRT parameters defined in the inverse planning procedure (fields

  7. Dural invasion by pituitary tumours.

    PubMed

    Shaffi, O M; Wrightson, P

    1975-04-23

    In 12 cases of pituitary tumour the dura mater of the sella turcica or diaphragma sellae in contact with the tumour was examined histologically. In nine cases tumour cells were found lying deep in the substance of the dura. Dura from the sella of seven subjects without pituitary disease, obtianed at autopsy, showed no inclusions of pituitary tissue. Four of the cases studied were known before death to suffer from an invasive pituitary adenoma. Of eight surviving cases operated upon in the last two years, five showed dural invasion by tumour. The present report suggests that the condition may be more frequent than expected and that with more study it may provide an index of prognosis. It also defines a requirement for the surgeon aiming to prevent recurrence of tumour after operation or to achieve a complete endocrine ablation.

  8. Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion.

    PubMed

    Sousa, Cristovão M; Biancur, Douglas E; Wang, Xiaoxu; Halbrook, Christopher J; Sherman, Mara H; Zhang, Li; Kremer, Daniel; Hwang, Rosa F; Witkiewicz, Agnes K; Ying, Haoqiang; Asara, John M; Evans, Ronald M; Cantley, Lewis C; Lyssiotis, Costas A; Kimmelman, Alec C

    2016-08-25

    Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by an intense fibrotic stromal response and deregulated metabolism. The role of the stroma in PDAC biology is complex and it has been shown to play critical roles that differ depending on the biological context. The stromal reaction also impairs the vasculature, leading to a highly hypoxic, nutrient-poor environment. As such, these tumours must alter how they capture and use nutrients to support their metabolic needs. Here we show that stroma-associated pancreatic stellate cells (PSCs) are critical for PDAC metabolism through the secretion of non-essential amino acids (NEAA). Specifically, we uncover a previously undescribed role for alanine, which outcompetes glucose and glutamine-derived carbon in PDAC to fuel the tricarboxylic acid (TCA) cycle, and thus NEAA and lipid biosynthesis. This shift in fuel source decreases the tumour’s dependence on glucose and serum-derived nutrients, which are limited in the pancreatic tumour microenvironment. Moreover, we demonstrate that alanine secretion by PSCs is dependent on PSC autophagy, a process that is stimulated by cancer cells. Thus, our results demonstrate a novel metabolic interaction between PSCs and cancer cells, in which PSC-derived alanine acts as an alternative carbon source. This finding highlights a previously unappreciated metabolic network within pancreatic tumours in which diverse fuel sources are used to promote growth in an austere tumour microenvironment. PMID:27509858

  9. Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion.

    PubMed

    Sousa, Cristovão M; Biancur, Douglas E; Wang, Xiaoxu; Halbrook, Christopher J; Sherman, Mara H; Zhang, Li; Kremer, Daniel; Hwang, Rosa F; Witkiewicz, Agnes K; Ying, Haoqiang; Asara, John M; Evans, Ronald M; Cantley, Lewis C; Lyssiotis, Costas A; Kimmelman, Alec C

    2016-08-25

    Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by an intense fibrotic stromal response and deregulated metabolism. The role of the stroma in PDAC biology is complex and it has been shown to play critical roles that differ depending on the biological context. The stromal reaction also impairs the vasculature, leading to a highly hypoxic, nutrient-poor environment. As such, these tumours must alter how they capture and use nutrients to support their metabolic needs. Here we show that stroma-associated pancreatic stellate cells (PSCs) are critical for PDAC metabolism through the secretion of non-essential amino acids (NEAA). Specifically, we uncover a previously undescribed role for alanine, which outcompetes glucose and glutamine-derived carbon in PDAC to fuel the tricarboxylic acid (TCA) cycle, and thus NEAA and lipid biosynthesis. This shift in fuel source decreases the tumour’s dependence on glucose and serum-derived nutrients, which are limited in the pancreatic tumour microenvironment. Moreover, we demonstrate that alanine secretion by PSCs is dependent on PSC autophagy, a process that is stimulated by cancer cells. Thus, our results demonstrate a novel metabolic interaction between PSCs and cancer cells, in which PSC-derived alanine acts as an alternative carbon source. This finding highlights a previously unappreciated metabolic network within pancreatic tumours in which diverse fuel sources are used to promote growth in an austere tumour microenvironment.

  10. Primary pulmonary solitary fibrous tumour with brain metastases.

    PubMed

    Ozeki, Naoki; Kawaguchi, Koji; Taniguchi, Tetsuo; Yokoi, Kohei

    2014-02-01

    Solitary fibrous tumour (SFT) is a mesenchymal neoplasm of subendothelial origin that can be found in all anatomical locations, but rarely in the lungs. A 71-year old female was referred to our hospital because of the increase in size of a solitary pulmonary mass. Chest contrast-enhanced dynamic computed tomography showed a well-circumscribed lobulated mass measuring 3.1×1.6 cm in the posterior segment of the right upper lobe of the lung. Positron emission tomography with 18F-fluorodeoxyglucose (FDG) demonstrated that the mass had high FDG uptake. A right upper lobectomy of the lung and mediastinal lymphadenectomy were performed. The tumour was pathologically diagnosed as an SFT. Seven months later, the patient was found to have brain metastases of the tumour, which led to dizziness. A craniotomy and successive radiosurgery with a gamma knife were performed for the metastatic tumours. She is still alive without evidence of disease 12 months after the treatment of the metastases. Pulmonary SFT seldom behaves aggressively, and only two previous cases of primary pulmonary SFT with brain metastases have been reported. Local therapy including surgery and radiotherapy against metastases from SFT could help improve the survival of such patients.

  11. Image-based computational quantification and visualization of genetic alterations and tumour heterogeneity.

    PubMed

    Zhong, Qing; Rüschoff, Jan H; Guo, Tiannan; Gabrani, Maria; Schüffler, Peter J; Rechsteiner, Markus; Liu, Yansheng; Fuchs, Thomas J; Rupp, Niels J; Fankhauser, Christian; Buhmann, Joachim M; Perner, Sven; Poyet, Cédric; Blattner, Miriam; Soldini, Davide; Moch, Holger; Rubin, Mark A; Noske, Aurelia; Rüschoff, Josef; Haffner, Michael C; Jochum, Wolfram; Wild, Peter J

    2016-01-01

    Recent large-scale genome analyses of human tissue samples have uncovered a high degree of genetic alterations and tumour heterogeneity in most tumour entities, independent of morphological phenotypes and histopathological characteristics. Assessment of genetic copy-number variation (CNV) and tumour heterogeneity by fluorescence in situ hybridization (ISH) provides additional tissue morphology at single-cell resolution, but it is labour intensive with limited throughput and high inter-observer variability. We present an integrative method combining bright-field dual-colour chromogenic and silver ISH assays with an image-based computational workflow (ISHProfiler), for accurate detection of molecular signals, high-throughput evaluation of CNV, expressive visualization of multi-level heterogeneity (cellular, inter- and intra-tumour heterogeneity), and objective quantification of heterogeneous genetic deletions (PTEN) and amplifications (19q12, HER2) in diverse human tumours (prostate, endometrial, ovarian and gastric), using various tissue sizes and different scanners, with unprecedented throughput and reproducibility. PMID:27052161

  12. Heavy ion tumour therapy

    NASA Astrophysics Data System (ADS)

    Scholz, M.

    2000-03-01

    Ion beams represent a promising radiotherapy modality for the treatment of deep seated tumours. Compared to conventional photon beams, in particular beams of heavier ions like e.g. carbon show several advantages which are related to their different physical and radiobiological properties: The dose increases with penetration depth and shows a sharp distal fall off at the end of the particle range, i.e., the depth dose profile is inverted compared to photon beams. They exhibit an increased biological effectiveness in particular at the end of their range and thus in the target volume. The spatial distribution of stopping particles can be monitored by means of PET-techniques making use of the small amount of radioactive projectile fragments. Ion beams were first used for medical applications in 1954 in Berkeley. Since then, several treatment facilities for tumour therapy have been established worldwide, and approximately 25 000 patients have been treated with protons and 3000 patients with heavier ions successfully. As an example, the specific advantages of the heavy ion therapy facility at GSI Darmstadt established in cooperation with the Radiological Clinics and DKFZ Heidelberg and FZ Rossendorf will be described. In contrast to most existing facilities, it is based on an active beam delivery system, using magnetic deflection of a pencil beam (raster scan) and accelerator energy variation to adjust the penetration depth. Thus, an optimal conformation of the dose to the target volume is achieved. PET-measurements allow for a quasi on-line monitoring of the 3D distribution of stopping particles and in particular of the position of the distal edge of the dose distribution. Furthermore, in the treatment planning procedure the radiobiological properties of ion beams are taken into account in great detail. In December 1997, patient treatments started at GSI, and up to now 42 patients were treated with carbon ions alone or in a mixed carbon/photon beam regime.

  13. Tumour imaging by the detection of fibrin clots in tumour stroma using an anti-fibrin Fab fragment.

    PubMed

    Obonai, Toshifumi; Fuchigami, Hirobumi; Furuya, Fumiaki; Kozuka, Naoyuki; Yasunaga, Masahiro; Matsumura, Yasuhiro

    2016-01-01

    The diagnosis of early and aggressive types of cancer is important for providing effective cancer therapy. Cancer-induced fibrin clots exist only within lesions. Previously, we developed a monoclonal antibody (clone 102-10) that recognizes insoluble fibrin but not fibrinogen or soluble fibrin and confirmed that fibrin clots form continuously in various cancers. Here, we describe the development of a Fab fragment probe of clone 102-10 for tumour imaging. The distribution of 102-10 Fab was investigated in genetically engineered mice bearing pancreatic ductal adenocarcinoma (PDAC), and its effect on blood coagulation was examined. Immunohistochemical and ex vivo imaging revealed that 102-10 Fab was distributed selectively in fibrin clots in PDAC tumours 3 h after injection and that it disappeared from the body after 24 h. 102-10 Fab had no influence on blood coagulation or fibrinolysis. Tumour imaging using anti-fibrin Fab may provide a safe and effective method for the diagnosis of invasive cancers by detecting fibrin clots in tumour stroma.

  14. Suppression of microRNA activity amplifies IFN-γ-induced macrophage activation and promotes anti-tumour immunity.

    PubMed

    Baer, Caroline; Squadrito, Mario Leonardo; Laoui, Damya; Thompson, Danielle; Hansen, Sarah K; Kiialainen, Anna; Hoves, Sabine; Ries, Carola H; Ooi, Chia-Huey; De Palma, Michele

    2016-07-01

    Tumour-associated macrophages (TAMs) largely express an alternatively activated (or M2) phenotype, which entails immunosuppressive and tumour-promoting capabilities. Reprogramming TAMs towards a classically activated (M1) phenotype may thwart tumour-associated immunosuppression and unleash anti-tumour immunity. Here we show that conditional deletion of the microRNA (miRNA)-processing enzyme DICER in macrophages prompts M1-like TAM programming, characterized by hyperactive IFN-γ/STAT1 signalling. This rewiring abated the immunosuppressive capacity of TAMs and fostered the recruitment of activated cytotoxic T lymphocytes (CTLs) to the tumours. CTL-derived IFN-γ exacerbated M1 polarization of Dicer1-deficient TAMs and inhibited tumour growth. Remarkably, DICER deficiency in TAMs negated the anti-tumoral effects of macrophage depletion by anti-CSF1R antibodies, and enabled complete tumour eradication by PD1 checkpoint blockade or CD40 agonistic antibodies. Finally, genetic rescue of Let-7 miRNA activity in Dicer1-deficient TAMs partly restored their M2-like phenotype and decreased tumour-infiltrating CTLs. These findings suggest that DICER/Let-7 activity opposes IFN-γ-induced, immunostimulatory M1-like TAM activation, with potential therapeutic implications. PMID:27295554

  15. Unravelling the neurophysiological basis of aggression in a fish model

    PubMed Central

    2010-01-01

    Background Aggression is a near-universal behaviour with substantial influence on and implications for human and animal social systems. The neurophysiological basis of aggression is, however, poorly understood in all species and approaches adopted to study this complex behaviour have often been oversimplified. We applied targeted expression profiling on 40 genes, spanning eight neurological pathways and in four distinct regions of the brain, in combination with behavioural observations and pharmacological manipulations, to screen for regulatory pathways of aggression in the zebrafish (Danio rerio), an animal model in which social rank and aggressiveness tightly correlate. Results Substantial differences occurred in gene expression profiles between dominant and subordinate males associated with phenotypic differences in aggressiveness and, for the chosen gene set, they occurred mainly in the hypothalamus and telencephalon. The patterns of differentially-expressed genes implied multifactorial control of aggression in zebrafish, including the hypothalamo-neurohypophysial-system, serotonin, somatostatin, dopamine, hypothalamo-pituitary-interrenal, hypothalamo-pituitary-gonadal and histamine pathways, and the latter is a novel finding outside mammals. Pharmacological manipulations of various nodes within the hypothalamo-neurohypophysial-system and serotonin pathways supported their functional involvement. We also observed differences in expression profiles in the brains of dominant versus subordinate females that suggested sex-conserved control of aggression. For example, in the HNS pathway, the gene encoding arginine vasotocin (AVT), previously believed specific to male behaviours, was amongst those genes most associated with aggression, and AVT inhibited dominant female aggression, as in males. However, sex-specific differences in the expression profiles also occurred, including differences in aggression-associated tryptophan hydroxylases and estrogen receptors

  16. 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.

  17. Pleomorphic adenoma of the nasopharyngeal mucosal space with locally aggressive appearance (2010: 11b).

    PubMed

    Downer, Jonathan; Fryer, Eve; Capper, John; Woo, Eric K

    2011-02-01

    Pleomorphic adenoma arising from submucosal minor salivary gland tissue in the head and neck is well described in the published literature. Where associated bone changes are present, benign-appearing bone remodelling is the rule, reflecting the slow growth of this benign tumour. Aggressive-appearing bone destruction was observed in this case. This atypical appearance has not been widely described.

  18. Circulating tumour cells and the epithelial mesenchymal transition in colorectal cancer.

    PubMed

    Lim, S H S; Becker, T M; Chua, W; Ng, W L; de Souza, P; Spring, K J

    2014-10-01

    Circulating tumour cells (CTCs) hold great potential as liquid biopsies to prognosticate disease and guide treatment in colorectal cancer. However, their emerging role in determining the molecular phenotype of tumour metastasis carries even more promising clinical use in the provision of comprehensive biomarker detection for targeted therapies and determination of drug resistance. The isolation of CTCs is technology dependent, and in the case of epithelial cell adhesion molecule-based platforms, the ability to detect cells that have undergone the epithelial to mesenchymal transition (EMT) is ineffective. CTCs displaying a mesenchymal phenotype are believed to have an increased metastatic potential. The rarity of CTCs provides another challenge in the enumeration of these cells. The future will likely involve the analysis of individual CTCs at any stage of the EMT in order to provide real-time phenotypic and molecular snapshots capable of tracking the dynamic evolution of tumour progression over time.

  19. Benign cardiac tumours, malignant arrhythmias

    PubMed Central

    Myers, Kimberley A; Wong, Kenny K; Tipple, Marion; Sanatani, Shubhayan

    2010-01-01

    Four cases of pediatric cardiac tumours (PCTs) associated with ventricular arrhythmias are reported. Sudden cardiac death attributable to the tumour occurred in two children. A third child received an implantable cardioverter defibrillator and the fourth had persistent ventricular arrhythmia despite medical therapy. Most PCTs are considered benign; however, the development of malignant arrhythmias may complicate the management of these tumours in some patients. The literature regarding the arrhythmogenic potential of PCTs and the use of implantable cardioverter defibrillators in these patients is reviewed. The series highlights the deficiency of prognostic information for this cohort. PMID:20151061

  20. Malignant tumours of the duodenum.

    PubMed

    Ryska, M; Hrabal, P

    2015-12-01

    No comprehensive knowledge of duodenal tumours exists in the current literature; individual types of malignant tumours may be described within malignancies of the small bowel, sets of case reports, or individual cases. Ampullary carcinomas are the exception and they are detailed in the current WHO histological classification of tumours of digestive system. Neither national nor international literature sources provide a comprehensive review of their therapy. The situation is similar when searching for surgical procedures. Resection procedures on the duodenum should thus be performed in specialized centres with sufficient experience with hepato-pancreato-biliary surgery. PMID:26767899

  1. The prevalence of aggression in genetic syndromes: a review.

    PubMed

    Powis, Laurie; Oliver, Chris

    2014-05-01

    Research into behavioural phenotypes identifies both environmental and organic factors as influencing aggression in children and adults with genetic disorders associated with intellectual disability. However, in contrast to self-injury there is a paucity of research that compares aggression across relevant syndromes. The primary aim of this review is to examine the association between aggression and genetic syndromes by analysis of prevalence studies. The review also examines the literature on the form of the behaviour and influence of environmental factors. Results imply that certain syndrome groups (Cri du Chat, Smith-Magenis, Prader-Willi, Angelman, Cornelia de Lange, and Fragile X syndromes; estimates over 70%) evidence a stronger association with aggression than others (e.g. Williams and Down syndromes; estimates below 15%). However, the strength of association is difficult to quantify due to methodological differences between studies. The results from examining form and environmental influences highlight the importance of phenotype-environment interactions. Research employing group comparison designs is warranted and future work on the assessment and intervention of aggression in genetic syndromes should consider the importance of phenotype-environment interactions. PMID:24594523

  2. Examining Genetic and Environmental Effects on Social Aggression: A Study of 6-Year-Old Twins

    ERIC Educational Resources Information Center

    Brendgen, Mara; Dionne, Ginette; Girard, Alain; Boivin, Michel; Vitaro, Frank; Prusse, Daniel

    2005-01-01

    Using a genetic design of 234 six-year-old twins, this study examined (a) the contribution of genes and environment to social versus physical aggression, and (b) whether the correlation between social and physical aggression can be explained by similar genetic or environmental factors or by a directional link between the phenotypes. For social…

  3. Role of genetic factors in the pathogenesis of aggressive periodontitis.

    PubMed

    Vieira, Alexandre R; Albandar, Jasim M

    2014-06-01

    This article critically reviews the evidence for a role of genetic factors in the pathogenesis of aggressive periodontitis and discusses the study approaches commonly used to identify genetic risk factors of this disease. Available data suggest that aggressive periodontitis is caused by mutations in multiple genes, combined with environmental effects. Syndromic periodontal diseases include certain monogenic disorders that express phenotypes showing aggressive forms of periodontitis, and the genetic triggering factors of most of these syndromes have been identified. Other periodontal disease phenotypes seem to occur through different genetic predisposition patterns. Case-control and genome-wide studies have been used to investigate the association with gene polymorphisms. Association studies and the familial aggregation of aggressive periodontitis suggest a significant genetic component in the increased predisposition to this disease. There is evidence to support the contribution of a few major genes or of multiple small-effects genes. In addition, there is evidence of gene-gene and gene-environment interaction effects. Early studies suggested an X-linked mode of transmission of aggressive periodontitis, and subsequent studies support an autosomal mode. Genetic studies have the potential to improve the screening programs of subjects at risk for developing aggressive periodontitis and may enhance treatment outcome through gene therapy.

  4. Intra-tumoural microvessel density in human solid tumours

    PubMed Central

    Hasan, J; Byers, R; Jayson, G C

    2002-01-01

    Over the last decade assessment of angiogenesis has emerged as a potentially useful biological prognostic and predictive factor in human solid tumours. With the development of highly specific endothelial markers that can be assessed in histological archival specimens, several quantitative studies have been performed in various solid tumours. The majority of published studies have shown a positive correlation between intra-tumoural microvessel density, a measure of tumour angiogenesis, and prognosis in solid tumours. A minority of studies have not demonstrated an association and this may be attributed to significant differences in the methodologies employed for sample selection, immunostaining techniques, vessel counting and statistical analysis, although a number of biological differences may account for the discrepancy. In this review we evaluate the quantification of angiogenesis by immunohistochemistry, the relationship between tumour vascularity and metastasis, and the clinicopathological studies correlating intra-tumoral microvessel density with prognosis and response to anti-cancer therapy. In view of the extensive nature of this retrospective body of data, comparative studies are needed to identify the optimum technique and endothelial antigens (activated or pan-endothelial antigens) but subsequently prospective studies that allocate treatment on the basis of microvessel density are required. British Journal of Cancer (2002) 86, 1566–1577. DOI: 10.1038/sj/bjc/6600315 www.bjcancer.com © 2002 Cancer Research UK PMID:12085206

  5. Rewiring macrophages for anti-tumour immunity.

    PubMed

    Lee, Yunqin; Biswas, Subhra K

    2016-06-28

    Tumour-associated macrophages facilitate cancer progression, but whether they can be reprogrammed to elicit an anti-tumour response remains unclear. Deletion of the microRNA-processing enzyme Dicer is now shown to rewire macrophages to an anti-tumour mode, leading to an enhanced response to immunotherapy and inhibition of tumour progression. PMID:27350442

  6. Experimental Functional Analysis of Aggression in Children with Angelman Syndrome

    ERIC Educational Resources Information Center

    Strachan, Rachel; Shaw, Rebecca; Burrow, Caroline; Horsler, Kate; Allen, Debbie; Oliver, Chris

    2009-01-01

    Background: Kinship theory suggests that genomic imprinting could account for phenotypic behaviors that increase (in the case of Angelman syndrome) or decrease (for Prader-Willi syndrome) the drive to access social resources (adult contact) depending on the imprinting parent-of-origin. Difficult to manage behaviors, such as aggression that is…

  7. Leydig cell tumours in childhood.

    PubMed

    Mengel, W; Knorr, D

    1983-01-01

    Two cases of Leydig cell tumours in childhood are presented. In one case, delayed diagnosis and operation led to pubertas praecox vera whereas in the other case normal growth and development occurred after early diagnosis and operation. PMID:6878724

  8. A rare benign ovarian tumour.

    PubMed

    Palmeiro, Marta Morna; Cunha, Teresa Margarida; Loureiro, Ana Luisa; Esteves, Gonçalo

    2016-01-01

    Sclerosing stromal tumour (SST) of the ovary is an extremely rare and benign ovarian neoplasm, accounting for 6% of the sex cord stromal ovarian tumours subtype. Usually, it is found during the second and third decades of life. Patients commonly present with pelvic pain, a palpable pelvic mass or menstrual irregularity. We report a case of a 20-year-old woman reporting of mild pelvic pain, with normal laboratory data. On imaging examinations, a large right adnexal tumour was found, with features suggesting an ovarian sex cord tumour. The patient underwent right salpingo-oophorectomy, diagnosing a SST of the ovary. This paper also reviews the literature, and emphasises the typical pathological and imaging characteristics of these rare benign ovarian lesions, and their impact, in a conservative surgery. PMID:26933186

  9. Multicellular Streaming in Solid Tumours

    NASA Astrophysics Data System (ADS)

    Kas, Josef

    As early as 400 BCE, the Roman medical encyclopaedist Celsus recognized that solid tumours are stiffer than surrounding tissue. However, cancer cell lines are softer, and softer cells facilitate invasion. This paradox raises several questions: Does softness emerge from adaptation to mechanical and chemical cues in the external microenvironment, or are soft cells already present inside a primary solid tumour? If the latter, how can a more rigid tissue contain more soft cells? Here we show that in primary tumour samples from patients with mammary and cervix carcinomas, cells do exhibit a broad distribution of rigidities, with a higher fraction of softer and more contractile cells compared to normal tissue. Mechanical modelling based on patient data reveals that, surprisingly, tumours with a significant fraction of very soft cells can still remain rigid. Moreover, in tissues with the observed distributions of cell stiffnesses, softer cells spontaneously self-organize into lines or streams, possibly facilitating cancer metastasis.

  10. Tumour of the juxtaoral organ.

    PubMed

    Bénateau, H; Rigau, V; Comoz, F; Benchemam, Y; Galateau, F; Compère, J F

    2003-02-01

    The juxtaoral organ is a normal and constant structure of the oral cavity. It consists of benign epithelial nests. We describe an intraoral tumour of the juxtaoral organ in a child. The tumour was not diagnosed after clinical and radiological examinations because it is extremely rare. A histological examination revealed a tumour of the juxtaoral organ, presumed to be neuroid hamartoma. This is only the second time that a tumour of the juxtaoral organ has been described in a child. We also describe the location, the embryology, the histology and the function of this organ. This is important because this structure can be confused with carcinomas of the oral cavity when examining frozen sections.

  11. Pituitary tumours: acromegaly.

    PubMed

    Chanson, Philippe; Salenave, Sylvie; Kamenicky, Peter; Cazabat, Laure; Young, Jacques

    2009-10-01

    Excessive production of the growth hormone (GH) is responsible for acromegaly. It is related to a pituitary GH-secreting adenoma in most cases. Prevalence is estimated 40-130 per million inhabitants. It is characterised by slowly progressive acquired somatic disfigurement (mainly involving the face and extremities) and systemic manifestations. The rheumatologic, cardiovascular, respiratory and metabolic consequences determine its prognosis. The diagnosis is confirmed by an increased serum GH concentration, unsuppressible by an oral glucose load and by detection of increased levels of insulin-like growth factor-I (IGF-I). Treatment is aimed at correcting (or preventing) tumour compression by excising the disease-causing lesion, and at reducing GH and IGF-I levels to normal values. When surgery, the usual first-line treatment, fails to correct GH/IGF-I hypersecretion, medical treatment with somatostatin analogues and/or radiotherapy can be used. The GH-receptor antagonist (pegvisomant) is helpful in patients who are resistant to somatostatin analogues. Thanks to this multistep therapeutic strategy, adequate hormonal disease control is achieved in most cases, allowing a normal life expectancy. PMID:19945023

  12. Imaging of skull base tumours.

    PubMed

    Thust, Stefanie Catherine; Yousry, Tarek

    2016-01-01

    The skull base is a highly complex and difficult to access anatomical region, which constitutes a relatively common site for neoplasms. Imaging plays a central role in establishing the differential diagnosis, to determine the anatomic tumour spread and for operative planning. All skull base imaging should be performed using thin-section multiplanar imaging, whereby CT and MRI can be considered complimentary. An interdisciplinary team approach is central to improve the outcome of these challenging tumours.

  13. Anti-tumour synergy of cytotoxic chemotherapy and anti-CD40 plus CpG-ODN immunotherapy through repolarization of tumour-associated macrophages.

    PubMed

    Buhtoiarov, Ilia N; Sondel, Paul M; Wigginton, Jon M; Buhtoiarova, Tatiana N; Yanke, Eric M; Mahvi, David A; Rakhmilevich, Alexander L

    2011-02-01

    We studied the effectiveness of monoclonal anti-CD40 + cytosine-phosphate-guanosine-containing oligodeoxynucleotide 1826 (CpG-ODN) immunotherapy (IT) in mice treated with multidrug chemotherapy (CT) consisting of vincristine, cyclophosphamide and doxorubicin. Combining CT with IT led to synergistic anti-tumour effects in C57BL/6 mice with established B16 melanoma or 9464D neuroblastoma. CT suppressed the functions of T cells and natural killer (NK) cells, but primed naïve peritoneal macrophages (Mφ) to in vitro stimulation with lipopolysaccharide (LPS), resulting in augmented nitric oxide (NO) production. IT, given after CT, did not restore the responsiveness of T cells and NK cells, but further activated Mφ to secrete NO, interferon-γ (IFN-γ) and interleukin (IL)-12p40 and to suppress the proliferation of tumour cells in vitro. These functional changes were accompanied by immunophenotype alterations on Mφ, including the up-regulation of Gr-1. CD11b(+) F4/80(+) Mφ comprised the major population of B16 tumour-infiltrating leucocytes. CT + IT treatment up-regulated molecules associated with the M1 effector Mφ phenotype [CD40, CD80, CD86, major histocompatibility complex (MHC) class II, IFN-γ, tumour necrosis factor-α (TNF-α) and IL-12] and down-regulated molecules associated with the M2 inhibitory Mφ phenotype (IL-4Rα, B7-H1, IL-4 and IL-10) on the tumour-associated Mφ compared with untreated controls. Together, the results show that CT and anti-CD40 + CpG-ODN IT synergize in the induction of anti-tumour effects which are associated with the phenotypic repolarization of tumour-associated Mφ.

  14. MRI characteristics of midbrain tumours.

    PubMed

    Sun, B; Wang, C C; Wang, J

    1999-03-01

    We diagnosed 60 cases of midbrain tumours by MRI between 1993 to 1997. There were 39 males and 21 females, aged 2-64 years, mean 25.6 years. We found 38 patients with true intramedullary mid-brain tumours, 11 predominantly in the tectum, 20 in the tegmentum and 7 with a downward extension to the pons; there were 7 within the cerebral aqueduct. There were 22 patients with infiltrating midbrain tumours extending from adjacent structures, 11 cases each from the thalamus and pineal region. All patients received surgical treatment. Gross total resection was achieved in 42 cases, subtotal (> 75 %) resection in 18. Pathological diagnoses included 16 low-grade and 15 high-grade astrocytomas; 5 oligodendroastrocytomas; 2 ependymomas; 11 glioblastomas; and 11 pineal parenchymal or germ-cell tumours. Midbrain tumours are a heterogeneous group of neoplasms, with wide variation in clinical and MRI features, related to the site and type of tumour. MRI not only allows precise analysis of their growth pattern, but also can lead to a correct preoperative diagnosis in the majority of cases.

  15. 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…

  16. 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…

  17. 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…

  18. 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…

  19. 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…

  20. 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…

  1. 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…

  2. 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…

  3. Squamous cell carcinoma of kidney co-existing with renal calculi: a rare tumour.

    PubMed

    Verma, Nidhi; Yadav, Gulabdhar; Dhawan, Nishi; Kumar, Awanish

    2011-03-01

    Squamous cell carcinoma (SCC) of urinary tract is a very rare tumour known to be associated with chronic renal calculi and infection. This tumour is highly aggressive and often detected at advanced stage with poor outcome. The authors describe a case report of a 62-year-old male patient who was diagnosed with right nephrolithiasis with non-functioning kidney. Histopathology revealed an unexpected co-existing SCC in renal pelvis. The present case highlights the careful search and use of newer imaging modalities in cases of long-standing renal calculi as they may have co-existing hidden malignancy which may change the treatment plan and prognosis.

  4. [Denosumab may be a supplement to the surgical treatment of giant cell tumours of bone].

    PubMed

    Sørensen, Anna Lynge; Hansen, Rehne Lessmann; Jørgensen, Peter Holmberg

    2016-09-01

    Giant cell tumour of bone (GCTB) is an aggressive bone tumour causing bone destruction. GCTB requires surgical treatment, and severe cases have a high risk of functional morbidity. GCTB consists of receptor activator of nuclear factor kappa-B (RANK)-positive osteoclast-like giant cells. The formation and activity of these cells are mediated by the interaction with RANK ligand (RANKL) released from neoplastic stromal cells. Denosumab is a human monoclonal antibody which inhibits RANKL and impairs the growth of the GCTB. Several studies have described the ability of denosumab to downgrade the extent of surgical treatment and improve the functional outcome. PMID:27593237

  5. The genetics of aggression: Where are we now?

    PubMed

    Asherson, Philip; Cormand, Bru

    2016-07-01

    Aggression, an overt behaviour with the intention to inflict damage, is a physiological trait with important roles throughout evolution, both in defence and predation. However, when expressed in humans in the wrong context, aggression leads to social maladjustment and crime. This special issue is about the genetic and neurobiological basis for aggression. Most of the 12 works presented here have been prepared by members of five international consortia established under the auspice of the FP7 and H2020 programs of the European Union to investigate different aspects of aggression and related behavioural phenotypes, including delineation of subtypes, aetiological mechanisms, neurobiology, neuroimaging, biomarkers, animal models and development and assessment of new treatments. Research on human aggression has largely focused on the societal causes of violent behaviour with relatively little focus on the underlying neuroscientific basis. However, interesting findings are emerging which suggest that by identifying distinct pathways to aggression, better targeting of social, psychological and medical treatments, can lead to improved outcomes for individuals and society. This issue represents a state of the art review of current neurobiological understanding of human aggression and a starting point for concerted efforts to move the field towards the development of new strategies for prevention and treatment. © 2016 Wiley Periodicals, Inc.

  6. 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)

  7. Therapy-induced tumour secretomes promote resistance and tumour progression

    PubMed Central

    Obenauf, Anna C.; Zou, Yilong; Ji, Andrew L.; Vanharanta, Sakari; Shu, Weiping; Shi, Hubing; Kong, Xiangju; Bosenberg, Marcus C.; Wiesner, Thomas; Rosen, Neal; Lo, Roger S.; Massagué, Joan

    2015-01-01

    Drug resistance invariably limits the clinical efficacy of targeted therapy with kinase inhibitors against cancer1,2. Here we show that targeted therapy with BRAF, ALK, or EGFR kinase inhibitors induces a complex network of secreted signals in drug-stressed melanoma and lung adenocarcinoma cells. This therapy-induced secretome (TIS) stimulates the outgrowth, dissemination, and metastasis of drug-resistant cancer cell clones and supports the survival of drug-sensitive cancer cells, contributing to incomplete tumour regression. The vemurafenib reactive secretome in melanoma is driven by down-regulation of the transcription factor FRA1. In situ transcriptome analysis of drug-resistant melanoma cells responding to the regressing tumour microenvironment revealed hyperactivation of multiple signalling pathways, most prominently the AKT pathway. Dual inhibition of RAF and PI3K/AKT/mTOR pathways blunted the outgrowth of the drug-resistant cell population in BRAF mutant melanoma tumours, suggesting this combination therapy as a strategy against tumour relapse. Thus, therapeutic inhibition of oncogenic drivers induces vast secretome changes in drug-sensitive cancer cells, paradoxically establishing a tumour microenvironment that supports the expansion of drug-resistant clones, but is susceptible to combination therapy. PMID:25807485

  8. Multiple tumours in survival estimates.

    PubMed

    Rosso, Stefano; De Angelis, Roberta; Ciccolallo, Laura; Carrani, Eugenio; Soerjomataram, Isabelle; Grande, Enrico; Zigon, Giulia; Brenner, Hermann

    2009-04-01

    In international comparisons of cancer registry based survival it is common practice to restrict the analysis to first primary tumours and exclude multiple cancers. The probability of correctly detecting subsequent cancers depends on the registry's running time, which results in different proportions of excluded patients and may lead to biased comparisons. We evaluated the impact on the age-standardised relative survival estimates of also including multiple primary tumours. Data from 2,919,023 malignant cancers from 69 European cancer registries participating in the EUROCARE-4 collaborative study were used. A total of 183,683 multiple primary tumours were found, with an overall proportion of 6.3% over all the considered cancers, ranging from 0.4% (Naples, Italy) to 12.9% (Iceland). The proportion of multiple tumours varied greatly by type of tumour, being higher for those with high incidence and long survival (breast, prostate and colon-rectum). Five-year relative survival was lower when including patients with multiple cancers. For all cancers combined the average difference was -0.4 percentage points in women and -0.7 percentage points in men, and was greater for older registries. Inclusion of multiple tumours led to lower survival in 44 out of 45 cancer sites analysed, with the greatest differences found for larynx (-1.9%), oropharynx (-1.5%), and penis (-1.3%). Including multiple primary tumours in survival estimates for international comparison is advisable because it reduces the bias due to different observation periods, age, registration quality and completeness of registration. The general effect of inclusion is to reduce survival estimates by a variable amount depending on the proportion of multiple primaries and cancer site.

  9. "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…

  10. Tumour spectrum in the FAMMM syndrome.

    PubMed Central

    Lynch, H. T.; Fusaro, R. M.; Pester, J.; Oosterhuis, J. A.; Went, L. N.; Rumke, P.; Neering, H.; Lynch, J. F.

    1981-01-01

    The Familial Atypical Multiple Mole-Melanoma Syndrome (FAMMM) is characterized by an autosomal dominantly inherited susceptibility to multiple atypical naevi. Patients with this hereditary phenotype show a strong susceptibility to cutaneous malignant melanoma (CMM). Our investigation of an extended Dutch kindred showing the FAMMM phenotype revealed a proband with bilateral intraocular malignant melanoma (IOM) and multiple CMM. The family revealed an array of tumours which included carcinoma of the lung, skin, larynx, and breast in addition to CMM and IOM, which were transmitted vertically through 3 generations. There was male-to-male transmission, and the number of affected males and females was about the same, which was consistent with an autosomal dominant inheritance. Thus the FAMMM syndrome not only indicates a potential for CMM, but a susceptibility to other systemic cancers as well. These observations, though limited to a single kindred, merit a painstaking evaluation of cancer of all anatomical sites in other kindreds showing the FAMMM syndrome. Such studies could yield clues to cancer aetiology, pathogenesis, and control. Images Fig. 2 Fig. 3 Fig. 4 PMID:7295511

  11. Institutional experience of paediatric high-grade central nervous system tumours: an analysis of 74 patients and review of the literature

    PubMed Central

    Oguz, Aynur; Karadeniz, Ceyda; Okur, Arzu; Sarac, Avni; Baykaner, Kemali; Bora, Huseyin; Poyraz, Aylar

    2012-01-01

    Aim of the study Although the survival for children with certain central nervous system (CNS) tumour types has improved through current surgical and adjuvant treatment modalities, the prognosis of many high-grade tumours remains poor despite aggressive treatment. The aim of this study is to analyse patients with high-grade brain tumours in our institution to determine the histopathology, clinical characteristics, treatment modalities, and survival. Material and methods A total of 74 patients with a diagnosis of high-grade brain tumour were analysed. There were a total of 31 patients with embryonal tumours, 27 patients with high-grade glial tumours, 12 patients with brain stem gliomas and 4 patients with other high-grade brain tumours. Results There were 48 (65%) boys and 26 (35%) girls (ratio: 1.85) with a median age of 99.7 months (range = 2-204 months). The median follow-up period was 19 months (range = 1-204 months). Tumour recurrence was observed in 38 patients (51.4%). The overall survival rate and event-free survival rate of our patients were 27% and 19.5%, respectively. Conclusions Pediatric high-grade CNS tumours have a very aggressive behaviour and a significant number of children eventually succumb to disease despite multimodal treatment. There is a need of more effective therapeutic approaches for these tumours with poor prognosis. The future improvement in childhood high-grade brain tumour management depends on a better understanding of the molecular genetics and biology of brain tumours. PMID:23788851

  12. 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

  13. Conference report from the 2015 OECI Oncology Days, Portugal, 22–24 June—tumour heterogeneity and next generation sequencing: morphology and technology

    PubMed Central

    Cairns, Linda

    2015-01-01

    Tumour heterogeneity was the topic of the ‘Oncology Days’ series held at the 2015 OECI conference in which experts within the field provided an update on tumour heterogeneity and its relevance in the clinical setting. Here we present a summary of the presentations from the two major sessions of the meeting: clonal heterogeneity and phenotypic heterogeneity. PMID:26316886

  14. Tenascin in salivary gland tumours.

    PubMed

    Soini, Y; Pääkkö, P; Virtanen, I; Lehto, V P

    1992-01-01

    The distribution of tenascin immunoreactivity was analysed in salivary gland tissue and in various benign and malignant tumours of the salivary gland. In the non-neoplastic tissue, tenascin was seen in the areas of basement membranes of the ductal epithelium. No immunoreactivity could be observed in the serous or mucous glands. In pleomorphic adenomas, tenascin immunoreactivity could be seen in the stromal compartment. It was more pronounced in the dense stromal areas and chondroid elements than in the myxoid area. In Warthin's tumours, strong tenascin immunoreactivity could be observed in the basement membrane zone of the epithelial component. In the lymphatic component, faint reticular staining could be seen. In adenoid cystic carcinomas, acinic cell tumours and mucoepidermoid carcinomas, tenascin showed a linear stromal distribution. No intracytoplasmic immunoreactivity could be seen in any of the cases. The widespread tenascin positivity in salivary gland tumours suggests that tenascin may play a role in the induction and progression of salivary gland tumours, presumably by interfering with the normal parenchymal-mesenchymal interaction.

  15. 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.

  16. [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.

  17. Pitfalls in colour photography of choroidal tumours

    PubMed Central

    Schalenbourg, A; Zografos, L

    2013-01-01

    Colour imaging of fundus tumours has been transformed by the development of digital and confocal scanning laser photography. These advances provide numerous benefits, such as panoramic images, increased contrast, non-contact wide-angle imaging, non-mydriatic photography, and simultaneous angiography. False tumour colour representation can, however, cause serious diagnostic errors. Large choroidal tumours can be totally invisible on angiography. Pseudogrowth can occur because of artefacts caused by different methods of fundus illumination, movement of reference blood vessels, and flattening of Bruch's membrane and sclera when tumour regression occurs. Awareness of these pitfalls should prevent the clinician from misdiagnosing tumours and wrongfully concluding that a tumour has grown. PMID:23238442

  18. Pitfalls in colour photography of choroidal tumours.

    PubMed

    Schalenbourg, A; Zografos, L

    2013-02-01

    Colour imaging of fundus tumours has been transformed by the development of digital and confocal scanning laser photography. These advances provide numerous benefits, such as panoramic images, increased contrast, non-contact wide-angle imaging, non-mydriatic photography, and simultaneous angiography. False tumour colour representation can, however, cause serious diagnostic errors. Large choroidal tumours can be totally invisible on angiography. Pseudogrowth can occur because of artefacts caused by different methods of fundus illumination, movement of reference blood vessels, and flattening of Bruch's membrane and sclera when tumour regression occurs. Awareness of these pitfalls should prevent the clinician from misdiagnosing tumours and wrongfully concluding that a tumour has grown.

  19. Tailored nanoparticles for tumour therapy.

    PubMed

    Jiang, Pei-Shin; Drake, Philip; Cho, Hui-Ju; Kao, Chao-Hung; Lee, Kun-Feng; Kuo, Chien-Hung; Lin, Xi-Zhang; Lin, Yuh-Jiuan

    2012-06-01

    Gd doped iron-oxide nanoparticles were developed for use in tumour therapy via magnetic fluid hyperthermia (MFH). The effect of the Gd3+ dopant on the particle size and magnetic properties was investigated. The final particle composition varied from Gd0.01Fe2.99O4 to Gd0.04Fe2.96O4 as determined by Inductively coupled plasma atomic emission spectroscopy (ICP-AES). TEM image analysis showed the average magnetic core diameters to be 12 nm and 33 nm for the lowest and highest Gd levels respectively. The specific power adsorption rate (SAR) determined with a field strength of 246 Oe and 52 kHz had a maximum of 38Wg(-1) [Fe] for the Gd0.03Fe2.97O4 sample. This value is about 4 times higher than the reported SAR values for Fe3O4. The potential for in vivo tumour therapy was investigated using a mouse model. The mouse models treated with Gd0.02Fe2.98O4 displayed much slower tumour growth after the first treatment cycle, the tumour had increased its mass by 25% after 7 days post treatment compared to a 79% mass increase over the same period for those models treated with standard iron-oxide or saline solution. After a second treatment cycle the mouse treated with Gd0.02Fe2.98O4 showed complete tumour regression with no tumour found for at least 5 days post treatment. PMID:22905580

  20. On the differential diagnosis of clear cell tumours of the head and neck.

    PubMed

    Eversole, L R

    1993-07-01

    Clear cell tumours, both benign and malignant, derive from a diverse group of epithelial cell types including renal epithelium, keratinising epithelium, cutaneous adnexa, salivary glands, odontogenic epithelium, melanocytes and even mesenchymally derived cells of adipose and tendon sheath. In the head and neck, clear cell tumours represent a singular challenge to the pathologist since the classic morphological features of malignant neoplasia exemplified by cytological atypia are frequently absent in malignant clear cell variants, thereby excluding reliance on this histopathological hallmark for the establishment of a diagnosis. The differential diagnosis of both benign and malignant clear cell tumours must take into account patterns of growth as well as the phenotype of accompanying cell populations when attempting to arrive at a definitive histological diagnosis. In this review article, the histopathology of head and neck tumours that harbour significant clear cell populations will be compared and contrasted.

  1. Tumour Microenvironment: Overview with an Emphasis on the Colorectal Liver Metastasis Pathway.

    PubMed

    Giakoustidis, Alexandros; Mudan, Satvinder; Hagemann, Thorsten

    2015-12-01

    The tumour microenvironment (TME) represents a dynamic network that plays an important role in tumour initiation, proliferation, growth, and metastasis. Cell behaviour may be regulated by interplay of molecular interactions involving positive and negative reinforcement as well as a high level of cross-talk, which determines this system. Additionally, cancer involves cell proliferation, its malignancy defined by the tumour's ability to break down normal tissue architecture and by a dynamic process of invasion and metastasis. The metastatic cascade is regulated by a chain of molecular steps which triggers the progression of the developing cancer cell in the primary tumour into a number of transformations, leading to invasion and proceeding to metastases. Tumour-associated macrophages (TAMs) play a key-role in the progression from inflammatory conditions to cancer; TAMs are also capable of infiltrating the tumour microenvironment. Furthermore, myeloid-derived suppressor cells (MDSCs), a population of inhibitory immune cells, have been reported to increase in various cancer types, although characterising human MDSCs remains difficult, as their phenotype is quite variable. The future of cancer treatment is likely to involve creating more drugs that target these elements as well as others. An overview of the tumour's microenvironment is, therefore, presented in this paper, focusing on the metastatic pathways of primary colorectal cancer to the liver.

  2. Use of haloperidol and risperidone in highly aggressive Swiss Webster mice by applying the model of spontaneous aggression (MSA).

    PubMed

    Fragoso, Viviane Muniz da Silva; Hoppe, Luanda Yanaan; de Araújo-Jorge, Tânia Cremonini; de Azevedo, Marcos José; Campos, Jerônimo Diego de Souza; Cortez, Célia Martins; de Oliveira, Gabriel Melo

    2016-03-15

    Aggression is defined as the act in which an individual intentionally harms or injures another of their own species. Antipsychotics are a form of treatment used in psychiatric routine. They have been used for decades in treatment of patients with aggressive behavior. Haloperidol and risperidone promote the control of psychiatric symptoms, through their respective mechanisms of action. Experimental models are obtained by behavioral, genetic, and pharmacological manipulations, and use a reduced number of animals. In this context, we applied the model of spontaneous aggression (MSA), originating the presence of highly aggressive mice (AgR) when reassembled in adulthood. We administered haloperidol and risperidone in escalating doses, for ten consecutive days. Using positive and negative control groups, we evaluated the effectiveness of these drugs and the reversal of the aggressive behavior, performing the tail suspension test (TST) and open field test (OFT) on 10th day of treatment and 10 days after its discontinuation. The results showed that both antipsychotic drugs were effective in AgR and reversed the aggressive phenotype, reducing the number of attacks by AgR and the extent of lesions in the subordinate mice (AgD) exposed to the pattern of aggressive behavior (PAB) of the aggressors. This conclusion is based on the reduction in the animals' motor and exploratory activity, and on the reversal of patterns of aggressive behavior. The association between the MSA and experiments with other therapeutic protocols and different antipsychotics can be an important methodology in the study of aggressive behavior in psychiatric patients. PMID:26698401

  3. Phyllodes tumour in pregnancy: a case report

    PubMed Central

    Way, Jeffrey C.; Culham, Beverley A.

    1998-01-01

    Phyllodes tumour (cystosarcoma phyllodes) is a rare breast tumour that grows rapidly and to a relatively large size, especially during pregnancy. These tumours may be classified as benign, borderline or malignant. They have a high incidence of local recurrence but little tendency to metastasize to distant organs. The question of whether the tumour is hormone dependent remains unresolved. This report describes the case of a patient who had a phyllodes tumour that first became apparent in her 31st week of pregnancy. After enucleation and subsequent wide excision she remained tumour free through a second pregnancy. Although the follow-up period is short, it appears that subsequent pregnancy is not necessarily associated with recurrent or new disease for patients who have had their initial tumour completely excised. The goal for the management of these tumours is complete surgical excision. PMID:9793511

  4. Heterospecific aggression bias towards a rarer colour morph.

    PubMed

    Lehtonen, Topi K; Sowersby, Will; Wong, Bob B M

    2015-09-22

    Colour polymorphisms are a striking example of phenotypic diversity, yet the sources of selection that allow different morphs to persist within populations remain poorly understood. In particular, despite the importance of aggression in mediating social dominance, few studies have considered how heterospecific aggression might contribute to the maintenance or divergence of different colour morphs. To redress this gap, we carried out a field-based study in a Nicaraguan crater lake to investigate patterns of heterospecific aggression directed by the cichlid fish, Hypsophrys nicaraguensis, towards colour polymorphic cichlids in the genus Amphilophus. We found that H. nicaraguensis was the most frequent territorial neighbour of the colour polymorphic A. sagittae. Furthermore, when manipulating territorial intrusions using models, H. nicaraguensis were more aggressive towards the gold than dark colour morph of the sympatric Amphilophus species, including A. sagittae. Such a pattern of heterospecific aggression should be costly to the gold colour morph, potentially accounting for its lower than expected frequency and, more generally, highlighting the importance of considering heterospecific aggression in the context of morph frequencies and coexistence in the wild. PMID:26378216

  5. 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

  6. Heterospecific aggression bias towards a rarer colour morph.

    PubMed

    Lehtonen, Topi K; Sowersby, Will; Wong, Bob B M

    2015-09-22

    Colour polymorphisms are a striking example of phenotypic diversity, yet the sources of selection that allow different morphs to persist within populations remain poorly understood. In particular, despite the importance of aggression in mediating social dominance, few studies have considered how heterospecific aggression might contribute to the maintenance or divergence of different colour morphs. To redress this gap, we carried out a field-based study in a Nicaraguan crater lake to investigate patterns of heterospecific aggression directed by the cichlid fish, Hypsophrys nicaraguensis, towards colour polymorphic cichlids in the genus Amphilophus. We found that H. nicaraguensis was the most frequent territorial neighbour of the colour polymorphic A. sagittae. Furthermore, when manipulating territorial intrusions using models, H. nicaraguensis were more aggressive towards the gold than dark colour morph of the sympatric Amphilophus species, including A. sagittae. Such a pattern of heterospecific aggression should be costly to the gold colour morph, potentially accounting for its lower than expected frequency and, more generally, highlighting the importance of considering heterospecific aggression in the context of morph frequencies and coexistence in the wild.

  7. Multiple cilia suppress tumour formation.

    PubMed

    Eberhart, Charles

    2016-04-01

    Primary cilia are cellular structures that have important functions in development and disease. The suppression of multiciliate differentiation of choroid plexus precursors, and maintenance of a single primary cilium by Notch1, is now shown to be involved in choroid plexus tumour formation. PMID:27027488

  8. Mixed tumour of the vagina.

    PubMed

    Fukunaga, M; Endo, Y; Ishikawa, E; Ushigome, S

    1996-05-01

    A 33-year-old Japanese woman presented with a polypoid 2.5 x 2.5 x 1.9 cm mass located in the posterior wall of the lower vagina. Microscopically, the tumour was composed of benign epithelial and stromal-type elements. Predominant epithelial elements were mucinous glands with squamous metaplasia and islands of mature squamous epithelium. The stromal-type cells showed reticular or short fascicular patterns with a transition to the epithelial elements. There was no dual epithelial-myoepithelial combination in the glands as seen in so-called mixed tumours (pleomorphic adenomas) of the salivary gland. Immunohistochemically, the epithelial elements were strongly positive for cytokeratin, PKK1 and epithelial membrane antigen, while the stromal-type cells co-expressed PKK1 and vimentin. Staining for S-100 protein, muscle actin, alpha-smooth muscle actin, desmin, and CD34 was uniformly negative in the tumour cells. The DNA pattern was diploid. The patient is alive and well without recurrence for 50 months after excision. These results indicate that an epithelial cell proliferation, probably of the remnant vestibular gland, plays a major role in the development of mixed tumours of the vagina.

  9. Rabaptin-5 and Rabex-5 are neoplastic tumour suppressor genes that interact to modulate Rab5 dynamics in Drosophila melanogaster☆

    PubMed Central

    Thomas, Chloe; Strutt, David

    2014-01-01

    Endocytosis plays an important role in the regulation of tumour growth and metastasis. In Drosophila, a number of endocytic neoplastic tumour suppressor genes have been identified that when mutated cause epithelial disruption and over-proliferation. Here we characterise the Drosophila homologue of the Rab5 effector Rabaptin-5, and show that it is a novel neoplastic tumour suppressor. Its ability to bind Rab5 and modulate early endosomal dynamics is conserved in Drosophila, as is its interaction with the Rab5 GEF Rabex5, for which we also demonstrate neoplastic tumour suppressor characteristics. Surprisingly, we do not observe disruption of apico-basal polarity in Rabaptin-5 and Rabex-5 mutant tissues; instead the tumour phenotype is associated with upregulation of Jun N-terminal Kinase (JNK) and Janus Kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) signalling. PMID:24104056

  10. Tumour vasculature--a potential therapeutic target.

    PubMed Central

    Baillie, C. T.; Winslet, M. C.; Bradley, N. J.

    1995-01-01

    The tumour vasculature is vital for the establishment, growth and metastasis of solid tumours. Its physiological properties limit the effectiveness of conventional anti-cancer strategies. Therapeutic approaches directed at the tumour vasculature are reviewed, suggesting the potential of anti-angiogenesis and the targeting of vascular proliferation antigens as cancer treatments. PMID:7543770

  11. 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

  12. [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.

  13. Putting tumours in context

    SciTech Connect

    Bissell, Mina J.; Radisky, Derek

    2001-10-01

    , the normal organization of the organ is replaced by a functional disorder. If there are pre-existing epithelial cells within this changing context that possess tumorigenic potential, they can start to proliferate. Alternatively, the abnormal interactions might lead to genomic instability within the epithelial cells and the acquisition of tumorigenic potential. The proliferating cancer cells can then interact with their microenvironment and enhance the abnormal interactions. At this point, the tumor has become its own organ, with a distinct context that now defines all its cellular responses. Here, we will examine how the mechanisms that contribute to the normal context also act to suppress developing tumors, how disruption of this context initiates and supports the process of tumorigenicity, and how some cells with a tumorigenic genotype can become phenotypically normal if the context is appropriately manipulated.

  14. 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

  15. Evolution of intratumoral phenotypic heterogeneity: the role of trait inheritance.

    PubMed

    Gallaher, Jill; Anderson, Alexander R A

    2013-08-01

    A tumour is a heterogeneous population of cells that competes for limited resources. In the clinic, we typically probe the tumour by biopsy, and then characterize it by the dominant genetic clone. But genotypes are only the first link in the chain of hierarchical events that leads to a specific cell phenotype. The relationship between genotype and phenotype is not simple, and the so-called genotype to phenotype map is poorly understood. Many genotypes can produce the same phenotype, so genetic heterogeneity may not translate directly to phenotypic heterogeneity. We therefore choose to focus on the functional endpoint, the phenotype as defined by a collection of cellular traits (e.g. proliferative and migratory ability). Here, we will examine how phenotypic heterogeneity evolves in space and time and how the way in which phenotypes are inherited will drive this evolution. A tumour can be thought of as an ecosystem, which critically means that we cannot just consider it as a collection of mutated cells but more as a complex system of many interacting cellular and microenvironmental elements. At its simplest, a growing tumour with increased proliferation capacity must compete for space as a limited resource. Hypercellularity leads to a contact-inhibited core with a competitive proliferating rim. Evolution and selection occurs, and an individual cell's capacity to survive and propagate is determined by its combination of traits and interaction with the environment. With heterogeneity in phenotypes, the clone that will dominate is not always obvious as there are both local interactions and global pressures. Several combinations of phenotypes can coexist, changing the fitness of the whole. To understand some aspects of heterogeneity in a growing tumour, we build an off-lattice agent-based model consisting of individual cells with assigned trait values for proliferation and migration rates. We represent heterogeneity in these traits with frequency distributions and

  16. Brief Report: Aggression and Stereotypic Behavior in Males with Fragile X Syndrome-- Moderating Secondary Genes in a "Single Gene" Disorder

    ERIC Educational Resources Information Center

    Hessl, David; Tassone, Flora; Cordeiro, Lisa; Koldewyn, Kami; McCormick, Carolyn; Green, Cherie; Wegelin, Jacob; Yuhas, Jennifer; Hagerman, Randi J.

    2008-01-01

    Although fragile X syndrome (FXS) is a single gene disorder with a well-described phenotype, it is not known why some individuals develop more significant maladaptive behaviors such as aggression or autistic symptoms. Here, we studied two candidate genes known to affect mood and aggression, the serotonin transporter (5-HTTLPR) and monoamine…

  17. Breast cancer nodal metastasis correlates with tumour and lymph node methylation profiles of Caveolin-1 and CXCR4.

    PubMed

    Alevizos, Leonidas; Kataki, Agapi; Derventzi, Anastasia; Gomatos, Ilias; Loutraris, Christos; Gloustianou, Georgia; Manouras, Andreas; Konstadoulakis, Manousos M; Zografos, George

    2014-06-01

    DNA methylation is the best characterised epigenetic change so far. However, its role in breast cancer metastasis has not as yet been elucidated. The aim of this study was to investigate the differences between the methylation profiles characterising primary tumours and their corresponding positive or negative for metastasis lymph nodes (LN) and correlate these with tumour metastatic potential. Methylation signatures of Caveolin-1, CXCR4, RAR-β, Cyclin D2 and Twist gene promoters were studied in 30 breast cancer primary lesions and their corresponding metastasis-free and tumour-infiltrated LN with Methylation-Specific PCR. CXCR4 and Caveolin-1 expression was further studied by immunohistochemistry. Tumours were typified by methylation of RAR-β and hypermethylation of Cyclin-D2 and Twist gene promoters. Tumour patterns were highly conserved in tumour-infiltrated LN. CXCR4 and Caveolin-1 promoter methylation patterns differentiated between node-negative and metastatic tumours. Nodal metastasis was associated with tumour and lymph node profiles of extended methylation of Caveolin-1 and lack of CXCR4 hypermethylation. Immunodetection studies verified CXCR4 and Caveolin-1 hypermethylation as gene silencing mechanism. Absence of Caveolin-1 expression in stromal cells associated with tumour aggressiveness while strong Caveolin-1 expression in tumour cells correlated with decreased 7-year disease-free survival. Methylation-mediated activation of CXCR4 and inactivation of Caveolin-1 was linked with nodal metastasis while intratumoral Caveolin-1 expression heterogeneity correlated with disease progression. This evidence contributes to the better understanding and, thereby, therapeutic management of breast cancer metastasis process.

  18. 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…

  19. Microsatellite-stable diploid carcinoma: a biologically distinct and aggressive subset of sporadic colorectal cancer

    PubMed Central

    Hawkins, N J; Tomlinson, I; Meagher, A; Ward, R L

    2001-01-01

    Chromosomal instability and microsatellite instability represent the major pathways for colorectal cancer (CRC) progression. However, a significant percentage of CRC shows neither pattern of instability, and thus represents a potentially distinctive form of the disease. Flow cytometry was used to determine the degree of DNA aneuploidy in 46 consecutive sporadic colorectal cancers. Microsatellite status was determined by PCR amplification using standard markers, while immunostaining was used to examine the expression of p53. K- ras status was determined by restriction-mediated PCR assay. Twenty-five (54%) tumours were aneuploid, 14 (30%) were diploid and microsatellite-stable and seven (15%) were diploid and microsatellite-unstable. Tumours with microsatellite instability were more likely to be right sided, to occur in women and to be associated with an improved survival. Aneuploid tumours were significantly more common in men and were likely to be left sided. The diploid microsatellite-stable (MSS) tumours did not show a sex or site predilection, but were strongly associated with the presence of metastatic disease at the time of diagnosis. Our data suggests that diploid, MSS tumours represent a biologically and phenotypically distinct subset of colorectal carcinoma, and one that is associated with the early development of metastases. We suggest that the genetic stability that characterizes these tumours may favour the maintenance of an invasive phenotype, and thus facilitate disease progression. These findings may have important implications for treatment options in this disease subset. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11161382

  20. 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.

  1. Gene expression and variation in social aggression by queens of the harvester ant Pogonomyrmex californicus.

    PubMed

    Helmkampf, Martin; Mikheyev, Alexander S; Kang, Yun; Fewell, Jennifer; Gadau, Jürgen

    2016-08-01

    A key requirement for social cooperation is the mitigation and/or social regulation of aggression towards other group members. Populations of the harvester ant Pogonomyrmex californicus show the alternate social phenotypes of queens founding nests alone (haplometrosis) or in groups of unrelated yet cooperative individuals (pleometrosis). Pleometrotic queens display an associated reduction in aggression. To understand the proximate drivers behind this variation, we placed foundresses of the two populations into social environments with queens from the same or the alternate population, and measured their behaviour and head gene expression profiles. A proportion of queens from both populations behaved aggressively, but haplometrotic queens were significantly more likely to perform aggressive acts, and conflict escalated more frequently in pairs of haplometrotic queens. Whole-head RNA sequencing revealed variation in gene expression patterns, with the two populations showing moderate differentiation in overall transcriptional profile, suggesting that genetic differences underlie the two founding strategies. The largest detected difference, however, was associated with aggression, regardless of queen founding type. Several modules of coregulated genes, involved in metabolism, immune system and neuronal function, were found to be upregulated in highly aggressive queens. Conversely, nonaggressive queens exhibited a striking pattern of upregulation in chemosensory genes. Our results highlight that the social phenotypes of cooperative vs. solitary nest founding tap into a set of gene regulatory networks that seem to govern aggression level. We also present a number of highly connected hub genes associated with aggression, providing opportunity to further study the genetic underpinnings of social conflict and tolerance.

  2. [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

  3. 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…

  4. 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…

  5. p53 Expression Helps Identify High Risk Oral Tongue Pre- malignant Lesions and Correlates with Patterns of Invasive Tumour Front and Tumour Depth in Oral Tongue Squamous Cell Carcinoma Cases.

    PubMed

    Viveka, Thangaraj Soundara; Shyamsundar, Vidyarani; Krishnamurthy, Arvind; Ramani, Pratibha; Ramshankar, Vijayalakshmi

    2016-01-01

    Oral tongue squamous cell carcinoma (OTSCC) is the most common oral cancer subtype with a maximum propensity for regional spread. Our objective was to study if p53 expression might have any correlation with aggressive patterns of invasion within oral tongue cancers as well as with the histologically identified degree of oral tongue dysplasia. p53 immunoexpression was studied using immunohistochemistry in early staged OTSCCs (n=155), oral tongue dysplasias, (n=29) and oral tongue normal specimens (n=10) and evaluated for correlations with histological and clinicopathological parameters. Our study (n=194) showed a pattern of p53 expression increasing with different grades of tongue dysplasia to different grades of invasive OTSCC (p=0.000). Among the OTSCC tumours, positive p53 expression was seen in 43.2% (67/155) and a higher p53 labelling index was significantly associated with increased Bryne's grade of the tumour invasive front (p=0.039) and increased tumour depth (p=0.018). Among the OTSCC patients with tobacco habits, (n=91), a higher p53 labelling index was significantly associated with increased risk of local recurrence (p=0.025) and with lymphovascular space involvement (p=0.014). Evaluation of p53 through varying degrees of dysplasia to oral tongue cancer indicates that p53 expression is linked to aggressive features of oral tongue cancers and tongue precancers entailing a closer monitoring in positive cases. Among the OTSCCs, p53 expression is associated with tumour aggressiveness correlating with increased grading of invasive tumour front and tumour depth.

  6. 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)

  7. 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…

  8. The invasive front of carcinomas. The most important area for tumour prognosis?

    PubMed

    Bryne, M; Boysen, M; Alfsen, C G; Abeler, V M; Sudbø, J; Nesland, J M; Kristensen, G B; Piffko, J; Bankfalvi, A

    1998-01-01

    Various molecular events of importance in tumour spread, like the gain and loss of adhesion molecules, secretion of proteolytic enzymes, increased cell proliferation, and the initiation of angiogenesis occur at the tumour-host interface (invasive front). We have hypothesised that molecular or morphological characteristics at the invasive front area of various carcinomas may reflect tumour prognosis better than other parts of the tumour. Consequently, we recently developed a simple malignancy grading system restricted to the deep invasive front area of head and neck squamous cell carcinomas. This grading system proved to have additional prognostic value over the established prognostic factors. All similar studies performed so far have confirmed the high prognostic significance of the invasive front grading in squamous cell carcinomas at different locations. In this review paper we describe the system and the hypothesis on which it has been developed. The reproducibility of the grading is acceptable for further extended studies. Interestingly, observations of similar invasive front alterations in different adenocarcinomas suggest that the invasive tumour front may underlie the biological aggressiveness of carcinomas of glandular origin, as well. PMID:9891553

  9. Diagnosing a rare case of desmoplastic small round cell tumour on liver biopsy.

    PubMed

    Cheo, F F; Leow, W Q

    2016-08-01

    A 50-year-old male of Indian descent presented with jaundice and right hypochondrium pain. Following a computed tomography (CT) scan of the abdomen, a segment 7 liver lesion was visualized, accompanied by extensive peritoneal tumour deposits. An ultrasound guided liver biopsy was performed and histology showed loose nests and sheets of tumour cells with a small blue round cell morphology. The tumour cells showed patchy strong immunopositivity for cytokeratins (AE1/3, CK7, CK19) and synaptophysin, while showing diffuse strong perinuclear positivity for desmin. Interphase fluorescence in-situ hybridization (FISH) study using EWSR1 breakapart probe was positive for EWSR1 gene rearrangement. Desmoplastic small round cell tumour is a rare but aggressive intra-abdominal mesenchymal tumour. While the primary sites of involvement are usually the peritoneum and omentum, visceral involvement can occur. We wish to highlight the importance of considering this entity when evaluating a liver biopsy especially in a less than classical clinical context. PMID:27568672

  10. Cell lines from MYCN transgenic murine tumours reflect the molecular and biological characteristics of human neuroblastoma.

    PubMed

    Cheng, Andy J; Cheng, Ngan Ching; Ford, Jette; Smith, Janice; Murray, Jayne E; Flemming, Claudia; Lastowska, Maria; Jackson, Michael S; Hackett, Christopher S; Weiss, William A; Marshall, Glenn M; Kees, Ursula R; Norris, Murray D; Haber, Michelle

    2007-06-01

    Overexpression of the human MYCN oncogene driven by a tyrosine hydroxylase promoter causes tumours in transgenic mice that recapitulate the childhood cancer neuroblastoma. To establish an in vitro model to study this process, a series of isogenic cell lines were developed from these MYCN-driven murine tumours. Lines were established from tumours arising in homozygous and hemizygous MYCN transgenic mice. Hemizygous tumours gave rise to cell lines growing only in suspension. Homozygous tumours gave rise to similar suspension lines as well as morphologically distinct substrate-adherent lines characteristic of human S-type neuroblastoma cells. FISH analysis demonstrated selective MYCN transgene amplification in cell lines derived from hemizygous mice. Comparative genomic hybridisation (CGH) and fluorescence in situ hybridisation (FISH) analysis confirmed a range of neuroblastoma-associated genetic changes in the various lines, in particular, gain of regions syntenic with human 17q. These isogenic lines together with the transgenic mice thus represent valuable models for investigating the biological characteristics of aggressive neuroblastoma.

  11. A preliminary investigation of the role of the transcription co-activators YAP/TAZ of the Hippo signalling pathway in canine and feline mammary tumours.

    PubMed

    Beffagna, G; Sacchetto, R; Cavicchioli, L; Sammarco, A; Mainenti, M; Ferro, S; Trez, D; Zulpo, M; Michieletto, S; Cecchinato, A; Goldschmidt, M; Zappulli, V

    2016-01-01

    Breast cancer is the most common cancer in women worldwide. Cancer metastases are responsible for the high mortality rate. A small but distinct subset of cells, cancer stem cells (CSCs), have the capacity to self-renew, initiate tumour formation, and develop metastases. The CSC content in human breast cancer correlates with the Hippo tumour suppressor signalling pathway. Specifically, the activity of YAP/TAZ, transcription co-activators of the Hippo pathway, sustains the self-renewal and tumour-initiation capacities of CSCs. Little is known about YAP/TAZ in canine and feline mammary tumours, which are very common tumours. The preliminary aim of the study was to investigate the expression of YAP/TAZ in canine and feline mammary tumours by Western blot and immunohistochemistry. Increased cytoplasmic and nuclear expression of YAP/TAZ was observed in all carcinomas compared to normal tissues, indicating neoplastic deregulation of the Hippo pathway. Nuclear expression significantly increased in grade III (high grade carcinomas) compared to grade I (low grade carcinomas) tumours, suggesting that YAP/TAZ play a role in the increased aggressiveness of these tumours. Moreover, different scoring systems for immunohistochemical analyses were compared and the H index and the Allred scores were the most significant. In conclusion, YAP/TAZ are expressed in aggressive canine and feline mammary tumours as reported in some human cancers. Further studies might better elucidate the role of the Hippo pathway in prognosis and as a target for new therapies. In addition, tumours in dogs and cats may be a useful model to study this pathway. PMID:26626094

  12. Proteomics of thyroid tumours provides new insights into their molecular composition and changes associated with malignancy

    PubMed Central

    Martínez-Aguilar, Juan; Clifton-Bligh, Roderick; Molloy, Mark P.

    2016-01-01

    Around 5% of the general population have palpable thyroid nodules. Although most thyroid tumours are benign, thyroid cancer represents the most common malignancy of the endocrine system, comprising mainly follicular and papillary thyroid carcinomas. Previous studies have shed some light on the molecular pathogenesis of thyroid cancer but there have not been any comprehensive mass spectrometry-based proteomic studies of large scale to reveal protein expression differences between thyroid tumours and the molecular alterations associated with tumour malignancy. We applied data-independent acquisition mass spectrometry which enabled quantitative expression analysis of over 1,600 proteins from 32 specimens to compare normal thyroid tissue with the three most common tumours of the thyroid gland: follicular adenoma, follicular carcinoma and papillary carcinoma. In follicular tumours, we found marked reduction of the tumour suppressor and therapeutic target extracellular protein decorin. We made the novel observation that TGFβ-induced protein ig-h3 (TGFBI) was found frequently overexpressed in follicular carcinoma compared with follicular adenoma. Proteomic pathway analysis showed changes in papillary carcinoma were associated with disruption of cell contacts (loss of E-cadherin), actin cytoskeleton dynamics and loss of differentiation markers, all hallmarks of an invasive phenotype. PMID:27025787

  13. Multiple molecular and cellular changes associated with tumour stasis and regression during IL-12 therapy of a murine breast cancer model.

    PubMed

    Dias, S; Thomas, H; Balkwill, F

    1998-01-01

    IL-12 treatment of a murine transplantable breast carcinoma (HTH-K) led to tumour regression and cure which was related to the duration of treatment. We studied the sequential molecular and phenotypic changes in IL-12-treated tumours. IFN-gamma mRNA was detected 8 hr after the first treatment. mRNA expression for the IFN-gamma-inducible genes beta 2-microglobulin and indoleamine dioxygenase (IDO) was induced subsequently, together with the chemokine IP-10. IL-12-treated tumours had an abundant cellular infiltrate, consisting mainly of CD8+ T cells. mRNA for granzyme B and perforin also could be detected, suggesting that those cells were activated. After 7 days of daily therapy, tumours in IL-12-treated mice had a significant reduction in vasculature. Finally, the number of apoptotic tumour cells increased throughout IL-12 treatment. We compared the anti-tumour effects of IL-12 to those induced by IFN-gamma therapy, which caused initial tumour stasis but subsequent tumour progression. IFN-gamma induced beta 2-microglobulin and IDO over a 7-day period, but IP-10 was induced only transiently. IFN-gamma caused a lesser cellular infiltrate, a minor anti-angiogenic effect and a transient apoptotic effect. The success of IL-12 may be due to its ability to produce a distinct sequence of molecular and phenotypic changes in tumours, leading to an anti-tumour immune response, toxicity against tumour cells and an anti-angiogenic effect. Other cytokines, such as IFN-gamma, induce some, but not all, of these actions. Comparison of IL-12 and IFN-gamma suggests that sustained induction of IP-10 and activation of a resulting cellular infiltrate may be key changes in regressing tumours. PMID:9426704

  14. Tumours of Oddi: Diagnosis and Surgical Treatment

    PubMed Central

    Jeppsson, B.; El-Khoury, W.; Hannoun, L.; Frileux, P.; Huguet, C.; Malafosse, M.; Parc, R.

    1992-01-01

    A retrospective review of 56 patients operated upon for tumours of Oddi was performed in order to determine optimal diagnostic and therapeutic procedures. Common presenting symptoms were jaundice (86%) and anemia (21%). Mean size of the tumour was 2.3 cm. Five tumours were benign and 51 were malignant. According to the classification of Martin, five were grade I: 10 grade II; 18 grade III; and 18 grade IV. Forty-seven patients underwent resection of the tumour: three local excisions for small benign tumors, six ampullectomies (followed in three by a Whipples’ procedure for recurrence) and 41 Whipples’ procedures. The hospital mortality was 5.3%, minor complications appeared in 21%. The overall five years survival was 41%. It was 75% in grade I, 50% in grade II, 40% in grade III and 10% in grade IV. The patients who received ampullectomies were alive with a follow-up of one, two and three years. All patients operated upon for a benign tumour were alive except one who died of cardiac failure. Ultrasonography and duodenoscopy are the most useful tests for the diagnosis of tumours of Oddi. Prognosis depends on the degree of infiltration of the duodenal wall and the presence of positive lymph nodes. Whipples’ procedure is best but ampullectomy can be used in elderly or poor risk patients. Malignant tumours of the ampullary region are infrequent and reported to constitute betwee 0.02 and five percent of all cancers of the digestive tract. With wider application of endoscopic techniques, there has been an increasing interest in this group of tumours during recent years. In the literature tumours of Oddi are usually reported in the group of periampullary tumours, including tumours of the ampulla itself, duodenal wall surrounding the ampulla, the distal part of the common bile duct and head of the pancreas. We have wanted to distinguish specifically the tumours of the ampulla of Vater and have adopted the term tumour of Oddi introduced by Marchal and Hureau

  15. Pott's puffy tumour: still not an eradicated entity.

    PubMed

    Guillén, A; Brell, M; Cardona, E; Claramunt, E; Costa, J M

    2001-05-01

    Pott's puffy tumour is an infrequent entity characterised by one or more subperiosteal abscesses associated with frontal bone osteomyelitis. Although cases in patients of all ages have been reported, teenagers are the most frequently affected. Early diagnosis and aggressive treatment are essential because of the high risk of severe neurological complications, such as epidural abscess, subdural empyema, and secondary septic thrombosis of the dural sinuses. This paper describes the case of a patient with a subperiosteal abscess resulting from sinusitis, with orbital and intracranial extension, and subsequent neurological complications. Despite modern methods of diagnosis and treatment, 13 new cases have been published in the last 5 years; in at least 3 (23%) of these cases there were serious neurological complications. Upper respiratory infections and sinusitis are leading causes of visits to the emergency department in the paediatric age group; however, no risk factors for poor outcome have so far been identified in any of these patients.

  16. Inflammatory myofibroblastic tumour of liver masquerading as hilar cholangiocarcinoma

    PubMed Central

    Subash, R; Arunkumar, ML; Iyoob, VA; Bonny, N

    2011-01-01

    There is a wide variety of inflammatory and benign neoplastic disorders of the biliary system that mimic cholangiocarcinoma in terms of clinical manifestations and imaging findings. Inflammatory myofibroblastic tumour of the bilary tract is one such condition, which is extremely rare but benign. Like cholangiocarcinoma this condition presents as painless progressive obstructive jaundice and it is often difficult to differentiate between the two prior to laparotomy, with the usual investigative modalities. Diagnosis is usually established by the characteristic histopathology findings in biopsy specimen. Newer diagnostic modalities directed at obtaining preoperative biopsy of the lesion appear promising in differentiating benign from malignant biliary lesions, but their routine use is yet to become standardised. Until then, awareness of doctors about the existence of such benign entities might prompt a less aggressive treatment approach while dealing with atypical hilar lesions of liver. PMID:24950398

  17. 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)…

  18. 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)

  19. 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.

  20. Psychophysiological correlates of aggression and violence: an integrative review.

    PubMed

    Patrick, Christopher J

    2008-08-12

    This paper reviews existing psychophysiological studies of aggression and violent behaviour including research employing autonomic, electrocortical and neuroimaging measures. Robust physiological correlates of persistent aggressive behaviour evident in this literature include low baseline heart rate, enhanced autonomic reactivity to stressful or aversive stimuli, enhanced EEG slow wave activity, reduced P300 brain potential response and indications from structural and functional neuroimaging studies of dysfunction in frontocortical and limbic brain regions that mediate emotional processing and regulation. The findings are interpreted within a conceptual framework that draws on two integrative models in the literature. The first is a recently developed hierarchical model of impulse control (externalizing) problems, in which various disinhibitory syndromes including aggressive and addictive behaviours of different kinds are seen as arising from common as well as distinctive aetiologic factors. This model represents an approach to organizing these various interrelated phenotypes and investigating their common and distinctive aetiologic substrates. The other is a neurobiological model that posits impairments in affective regulatory circuits in the brain as a key mechanism for impulsive aggressive behaviour. This model provides a perspective for integrating findings from studies employing different measures that have implicated varying brain structures and physiological systems in violent and aggressive behaviour. PMID:18434285

  1. A rare case of aggressive squamous cell carcinoma of the bladder in pregnancy

    PubMed Central

    Dieh, A

    2013-01-01

    We report a rare case of an aggressive squamous cell carcinoma of the bladder in a young primigravid woman with recurrent urinary tract infections and microscopic haematuria. An emergency caesarean section was performed at 37 weeks gestation for suspected placental abruption; however, she was found to have frank haematuria. Postnatally, an advanced bladder tumour was diagnosed. She required renal dialysis, a radical cystectomy and radiotherapy but sadly died seven months after diagnosis. This case illustrates the importance of thorough investigation of haematuria in pregnancy. Cystoscopy and even tumour resection can be safely performed in pregnancy. Although squamous cell carcinomas account for only 2% of bladder tumours in developed countries, they tend to be large and deeply invasive, requiring radical surgery and chemotherapy or radiotherapy. Management should be multidisciplinary and treatment individualized due to the significant clinical and emotional challenges which arise when a woman develops a malignancy in pregnancy or the puerperium.

  2. The etiology of the association between child antisocial behavior and maternal negativity varies across aggressive and non-aggressive rule-breaking forms of antisocial behavior

    PubMed Central

    Klahr, Ashlea M.; Klump, Kelly L.; Burt, S. Alexandra

    2014-01-01

    There is a robust association between negative parenting and child antisocial behavior problems. However, the etiology of this association remains unclear. Extant literature has reported strikingly different conclusions across studies, with some highlighting genetic mediation and others highlighting environmental mediation. One possible reason for these discrepancies across studies may be the failure to differentiate between aggressive and non-aggressive (rule-breaking) dimensions of childhood antisocial behavior, given their notably different etiologies and developmental trajectories (Burt, 2012). The current study sought to examine the phenotypic and etiologic associations of maternal negativity with aggressive and rule-breaking antisocial behavior, respectively. Participants included 824 mothers and their twin children between the ages of 6 and 10. Our results highlighted clear etiologic distinctions in the associations of aggression and rule-breaking with maternal negativity. Aggression was associated with maternal negativity via both genetic and environmental factors, whereas the association between non-aggressive rule-breaking and maternal negativity was entirely environmental in origin. These findings provide additional support for the presence of meaningful distinctions between aggressive and non-aggressive forms of antisocial behavior, and highlight the complex relationship between parenting and child outcome. PMID:24906982

  3. The etiology of the association between child antisocial behavior and maternal negativity varies across aggressive and non-aggressive rule-breaking forms of antisocial behavior.

    PubMed

    Klahr, Ashlea M; Klump, Kelly L; Burt, S Alexandra

    2014-11-01

    There is a robust association between negative parenting and child antisocial behavior problems. However, the etiology of this association remains unclear. Extant literature has reported strikingly different conclusions across studies, with some highlighting genetic mediation and others highlighting environmental mediation. One possible reason for these discrepancies across studies may be the failure to differentiate between aggressive and non-aggressive (rule-breaking) dimensions of childhood antisocial behavior, given their notably different etiologies and developmental trajectories (Burt 2012). The current study sought to examine the phenotypic and etiologic associations of maternal negativity with aggressive and rule-breaking antisocial behavior, respectively. Participants included 824 mothers and their twin children between the ages of 6 and 10. Our results highlighted clear etiologic distinctions in the associations of aggression and rule-breaking with maternal negativity. Aggression was associated with maternal negativity via both genetic and environmental factors, whereas the association between non-aggressive rule-breaking and maternal negativity was entirely environmental in origin. These findings provide additional support for the presence of meaningful distinctions between aggressive and non-aggressive forms of antisocial behavior, and highlight the complex relationship between parenting and child outcome.

  4. Tumour angiogenesis is reduced in the Tc1 mouse model of Down's syndrome.

    PubMed

    Reynolds, Louise E; Watson, Alan R; Baker, Marianne; Jones, Tania A; D'Amico, Gabriela; Robinson, Stephen D; Joffre, Carine; Garrido-Urbani, Sarah; Rodriguez-Manzaneque, Juan Carlos; Martino-Echarri, Estefanía; Aurrand-Lions, Michel; Sheer, Denise; Dagna-Bricarelli, Franca; Nizetic, Dean; McCabe, Christopher J; Turnell, Andrew S; Kermorgant, Stephanie; Imhof, Beat A; Adams, Ralf; Fisher, Elizabeth M C; Tybulewicz, Victor L J; Hart, Ian R; Hodivala-Dilke, Kairbaan M

    2010-06-10

    Down's syndrome (DS) is a genetic disorder caused by full or partial trisomy of human chromosome 21 and presents with many clinical phenotypes including a reduced incidence of solid tumours. Recent work with the Ts65Dn model of DS, which has orthologues of about 50% of the genes on chromosome 21 (Hsa21), has indicated that three copies of the ETS2 (ref. 3) or DS candidate region 1 (DSCR1) genes (a previously known suppressor of angiogenesis) is sufficient to inhibit tumour growth. Here we use the Tc1 transchromosomic mouse model of DS to dissect the contribution of extra copies of genes on Hsa21 to tumour angiogenesis. This mouse expresses roughly 81% of Hsa21 genes but not the human DSCR1 region. We transplanted B16F0 and Lewis lung carcinoma tumour cells into Tc1 mice and showed that growth of these tumours was substantially reduced compared with wild-type littermate controls. Furthermore, tumour angiogenesis was significantly repressed in Tc1 mice. In particular, in vitro and in vivo angiogenic responses to vascular endothelial growth factor (VEGF) were inhibited. Examination of the genes on the segment of Hsa21 in Tc1 mice identified putative anti-angiogenic genes (ADAMTS1and ERG) and novel endothelial cell-specific genes, never previously shown to be involved in angiogenesis (JAM-B and PTTG1IP), that, when overexpressed, are responsible for inhibiting angiogenic responses to VEGF. Three copies of these genes within the stromal compartment reduced tumour angiogenesis, explaining the reduced tumour growth in DS. Furthermore, we expect that, in addition to the candidate genes that we show to be involved in the repression of angiogenesis, the Tc1 mouse model of DS will permit the identification of other endothelium-specific anti-angiogenic targets relevant to a broad spectrum of cancer patients. PMID:20535211

  5. Mutations in the p53 gene occur in diverse human tumour types.

    PubMed

    Nigro, J M; Baker, S J; Preisinger, A C; Jessup, J M; Hostetter, R; Cleary, K; Bigner, S H; Davidson, N; Baylin, S; Devilee, P

    1989-12-01

    The p53 gene has been a constant source of fascination since its discovery nearly a decade ago. Originally considered to be an oncogene, several convergent lines of research have indicated that the wild-type gene product actually functions as a tumour suppressor gene. For example, expression of the neoplastic phenotype is inhibited, rather than promoted, when rat cells are transfected with the murine wild-type p53 gene together with mutant p53 genes and/or other oncogenes. Moreover, in human tumours, the short arm of chromosome 17 is often deleted. In colorectal cancers, the smallest common region of deletion is centred at 17p13.1; this region harbours the p53 gene, and in two tumours examined in detail, the remaining (non-deleted) p53 alleles were found to contain mutations. This result was provocative because allelic deletion coupled with mutation of the remaining allele is a theoretical hallmark of tumour-suppressor genes. In the present report, we have attempted to determine the generality of this observation; that is, whether tumours with allelic deletions of chromosome 17p contain mutant p53 genes in the allele that is retained. Our results suggest that (1) most tumours with such allelic deletions contain p53 point mutations resulting in amino-acid substitutions, (2) such mutations are not confined to tumours with allelic deletion, but also occur in at least some tumours that have retained both parental 17p alleles, and (3) p53 gene mutations are clustered in four 'hot-spots' which exactly coincide with the four most highly conserved regions of the gene. These results suggest that p53 mutations play a role in the development of many common human malignancies.

  6. Therapeutic vaccine generated by electrofusion of dendritic cells and tumour cells.

    PubMed

    Kuriyama, H; Shimizu, K; Lee, W; Kjaergaard, J; Parkhurst, M R; Cohen, P A; Shu, S

    2004-01-01

    Immunotherapy with fusion of dendritic cells (DCs) and tumour cells potentially confers the advantages of DC antigen-presenting functionality and a continuous source of unaltered tumour antigens. However, fusion using chemical or viral fusogens has been inefficient. We have recently developed a high throughput electrofusion technique with which very efficient fusion rates (15-54%) were observed in over 300 experiments, using a variety of murine and human tumour cell lines. The fused cells display a mature DC phenotype and express tumour-associated antigens. In two pre-clinical animal models (B16 melanoma transduced with the LacZ gene and the MCA 205 fibrosarcoma), a single vaccination of mice bearing tumours established in the lung, brain and skin resulted in tumour regression and prolongation of life. However, therapeutic efficacy required the administration of adjuvants such as IL-12 and OX-40R mAbs. Effective immunotherapy also required the delivery of fusion cells directly into lymphoid organs (spleen or lymph nodes). Using five defined human T cell lines derived from melanoma patients, allogeneic DCs of HLA-A2, HLA-DR4 and HLA-DR7 haplotypes fused with MART-1, gp100, tyrosinase and TRP-2 expressing 888 mel melanoma cells were analysed for their ability to stimulate specific cytokine (IFN-gamma and GM-CSF) secretion. DC-888 mel hybrids presented all tumour-associated epitopes to both CD4 and CD8 T cell lines in the context of MHC class II and I molecules, respectively. The therapeutic efficacy of a DC-tumour fusion vaccine is now being evaluated for the treatment of metastatic melanoma. PMID:15603192

  7. 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

  8. Benign tumours of the bone: A review☆

    PubMed Central

    Hakim, David N.; Pelly, Theo; Kulendran, Myutan; Caris, Jochem A.

    2015-01-01

    Benign tumours of the bone are not cancerous and would not metastasise to other regions of the body. However, they can occur in any part of the skeleton, and can still be dangerous as they may grow and compress healthy bone tissue. There are several types of benign tumours that can be classified by the type of matrix that the tumour cells produce; such as bone, cartilage, fibrous tissue, fat or blood vessel. Overall, 8 different types can be distinguished: osteochondroma, osteoma, osteoid osteoma, osteoblastoma, giant cell tumour, aneurysmal bone cyst, fibrous dysplasia and enchondroma. The incidence of benign bone tumours varies depending on the type. However, they most commonly arise in people less than 30 years old, often triggered by the hormones that stimulate normal growth. The most common type is osteochondroma. This review discusses the different types of common benign tumours of the bone based on information accumulated from published literature. PMID:26579486

  9. Solitary fibrous tumour: a diagnostic dilemma.

    PubMed

    Ghosh, Sharmila; Shet, Tanuja M; Chinoy, R F; Kane, S V

    2007-07-01

    Solitary fibrous tumour (SFT) is a rare spindle cell neoplasm arising at pleural and extrapleural sites. Five cases of SFT diagnosed at our institution over a five year period were reviewed. Haematoxylin and eosin stained histological sections, immuno-histochemical markers including CD34 and electron microscopy were the different methods used to study these tumours. Three histological features were consistently observed in all the tumours: the tumours were composed of short spindle cells separated by dense collagen bands and arranged in alternate hypocellular and hypercellular areas. CD34 positivity was seen in all the cases. SFT's have been reported to behave in an unpredictable fashion and hence prolonged follow up is essential. Histology, CD34 positivity and electron microscopy are useful tools in diagnosing SFT. While the pleural tumours can be diagnosed based on histology, this must be substantiated by ancillary techniques in case of extrapleural tumours.

  10. Female aggression predicts mode of paternity acquisition in a social lizard

    PubMed Central

    While, Geoffrey M.; Sinn, David L.; Wapstra, Erik

    2009-01-01

    Individual differences in behaviour are ubiquitous in nature. Despite the likely role of selection in maintaining these differences, there are few demonstrations of their fitness consequences in wild populations and, consequently, the mechanisms that link behavioural variation to variation in fitness are poorly understood. Specifically, the consequences of consistent individual differences in behaviour for the evolution of social and mating strategies have rarely been considered. We examined the functional links between variation in female aggression and her social and mating strategies in a wild population of the social lizard Egernia whitii. We show that female Egernia exhibit temporally consistent aggressive phenotypes, which are unrelated to body size, territory size or social density. A female's aggressive phenotype, however, has strong links to her mode of paternity acquisition (within- versus extra-pair paternity), with more aggressive females having more offspring sired by extra-pair males than less aggressive females. We discuss the potential mechanisms by which female aggression could underpin mating strategies, such as the pursuit/acceptance of extra-pair copulations. We propose that a deeper understanding of the evolution and maintenance of social and mating systems may result from an explicit focus on individual-level female behavioural phenotypes and their relationship with key reproductive strategies. PMID:19324771

  11. 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.

  12. [Solitary fibrous tumours of the kidney].

    PubMed

    Gres, Pascal; Avances, Christophe; Ben Naoum, Kamel; Chapuis, Héliette; Costa, Pierre

    2004-02-01

    Solitary fibrous tumours (SFT) are mesenchymal tumours that usually arise from the pleura. Renal SFT are exceptional (9 cases reported in the literature). The authors report a new case discovered during assessment of HT and treated by radical right nephrectomy. The histological appearance is characteristic: a tumour with a fibrous centre, composed of a monomorphic proliferation of spindle cells, with positive CD 34, CD 99, and bcl 2 labelling. The prognosis after complete resection is generally favourable.

  13. Solitary fibrous tumour of the tongue.

    PubMed

    Piattelli, A; Fioroni, M; Rubini, C

    1998-09-01

    Solitary fibrous tumour (SFT) is a neoplasm most often localised in the pleura and peritoneum. The tumour is composed of spindled fibroblastic cells arranged in a haphazard way. Recently SFT has been described in many locations. Only one case of oral SFT has been described in the cheek: this is the second case of an oral SFT located in the tongue. The differential diagnosis must be made from many soft tissue tumours. SFTs stain strongly, in almost all cases, for CD34.

  14. [Adenomatoid tumour of the adrenal gland].

    PubMed

    Bandier, Philippe Claus; Hansen, Alastair; Thorelius, Lars

    2009-01-26

    An adenomatoid tumour in the right suprarenal gland was discovered during clinical cancer staging of a 73-year-old woman. Adenomatoid tumours in the suprarenal glands are rare and are most often found incidentally. A definitive diagnosis is made on the basis of histology since imaging methods are non-specific. Differential diagnoses comprise malignant vascular neoplasm or adenocarcinoma. Immunohistochemistry or electron microscopy allows uncomplicated distinction between these tumours. In general, it is recommended to obtain biopsies from suprarenal processes.

  15. A Hybrid Cellular Automaton Model of Clonal Evolution in Cancer: The Emergence of the Glycolytic Phenotype

    PubMed Central

    Gerlee, P.; Anderson, A.R.A.

    2009-01-01

    We present a cellular automaton model of clonal evolution in cancer aimed at investigating the emergence of the glycolytic phenotype. In the model each cell is equipped with a micro-environment response network that determines the behaviour or phenotype of the cell based on the local environment. The response network is modelled using a feed-forward neural network, which is subject to mutations when the cells divide. This implies that cells might react differently to the environment and when space and nutrients are limited only the fittest cells will survive. With this model we have investigated the impact of the environment on the growth dynamics of the tumour. In particular we have analysed the influence of the tissue oxygen concentration and extra-cellular matrix density on the dynamics of the model. We found that the environment influences both the growth and evolutionary dynamics of the tumour. For low oxygen concentration we observe tumours with a fingered morphology, while increasing the matrix density gives rise to more compact tumours with wider fingers. The distribution of phenotypes in the tumour is also affected, and we observe that the glycolytic phenotype is most likely to emerge in a poorly oxygenated tissue with a high matrix density. Our results suggest that it is the combined effect of the oxygen concentration and matrix density that creates an environment where the glycolytic phenotype has a growth advantage and consequently is most likely to appear. PMID:18068192

  16. Evolution of cell motility in an individual-based model of tumour growth

    PubMed Central

    Gerlee, P.; Anderson, A.R.A.

    2009-01-01

    Tumour invasion is driven by proliferation and importantly migration into the surrounding tissue. Cancer cell motility is also critical in the formation of metastases and is therefore a fundamental issue in cancer research. In this paper we investigate the emergence of cancer cell motility in an evolving tumour population using an individual-based modelling approach. In this model of tumour growth each cell is equipped with a microenvironment response network that determines the behaviour or phenotype of the cell based on the local environment. The response network is modelled using a feed-forward neural network, which is subject to mutations when the cells divide. With this model we have investigated the impact of the micro-environment on the emergence of a motile invasive phenotype. The results show that when a motile phenotype emerges the dynamics of the model are radically changed and we observe faster growing tumours exhibiting diffuse morphologies. Further we observe that the emergence of a motile subclone can occur in a wide range of micro-environmental growth conditions. Iterated simulations showed that in identical growth conditions the evolutionary dynamics either converge to a proliferating or migratory phenotype, which suggests that the introduction of cell motility into the model changes the shape of fitness landscape on which the cancer cell population evolves and that it now contains several local maxima. This could have important implications for cancer treatments which focus on the gene level, as our results show that several distinct genotypes and critically distinct phenotypes can emerge and become dominant in the same micro-environment. PMID:19285513

  17. Gastric stromal tumours: a practical approach.

    PubMed Central

    Mihssin, N.; Moorthy, K.; Sengupta, A.; Houghton, P. W.

    2000-01-01

    Recent findings on the pathological diversity of gastric stromal tumours and their unpredictable behaviour prompted us to review our series of 16 patients who had undergone surgery for these tumours from 1991 to 1998. There were 13 benign and 3 malignant lesions. The majority of patients presented with either upper gastrointestinal bleeding or anaemia alone (12 of 16). Endoscopy was an extremely useful diagnostic tool, revealing the lesion as an intraluminal protuberant tumour with or without ulcer in 10 cases and as an ulcer alone in 4 cases, and in 1 case features suggesting an extrinsic mass. All the patients in the series underwent surgery. We used staplers (AutosutureR TA 55) to excise the tumours in 7 cases, all of which on histological examination were benign with clear resection margins. Gastric resections were performed in 5 cases for either large tumours or those situated at the fundus or antrum and local excision of the remaining 4. The mean follow-up of these patients was 24 months. Two patients with malignant lesions died of irresectable recurrences, one 2 months and one 18 months after surgery. There have been no recurrences in the tumours diagnosed as benign on histology. Tumour size, position and the ability to apply the stapler leaving adequate margin below the tumour should be the determinants of extent and type of excision. Reliable determinants of behaviour are tumour size, grade and mitotic index. Images Figure 1 PMID:11103152

  18. Solitary fibrous tumour of the pleura.

    PubMed

    Sikri, V; Chawla, R

    2013-01-01

    Solitary fibrous tumour (SFT) of the pleura is a rare, usually benign primary tumour of the pleura. Spectrum of presentation can vary from an incidental finding on chest radiograph done for some other purpose, features of compression of surrounding structures to symptoms resulting from the tumour per se. We report a case of a female who presented with complaints of cough and chest pain in whom a diagnosis of SFT was confirmed on tru-cut biopsy and immunohistochemistry studies. The patient underwent thoracotomy and successful removal of the tumour.

  19. Oncogenic osteomalacia: strange tumours in strange places.

    PubMed Central

    Weiss, D.; Bar, R. S.; Weidner, N.; Wener, M.; Lee, F.

    1985-01-01

    Two patients presented with hypophosphataemic osteomalacia and were subsequently found to have small tumours unusual histopathology and location causing the osteomalacia. Each tumour was found after an intensive search for occult masses. Studies of vitamin D metabolism and renal tubular function before and after surgery yielded further insight into the pathophysiology of oncogenic osteomalacia. These cases demonstrate that microscopic quantities of tumour are capable of causing the syndrome and further illustrate the high index of suspicion often necessary to locate causative tumours in patients with hypophosphataemic osteomalacia. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:4022870

  20. 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

  1. [Pancreatic tumour in a child].

    PubMed

    Schouenborg Schultz, Thea; Thyssen Vestergaard, Esben

    2014-07-28

    Abdominal pain is a common symptom in children and recurrent abdominal pain (RAP) has a prevalence of 8.4% in childhood. In 90-95% of RAPs no organic disease is identified. Thus, it is important that the few of somatic origin are diagnosed. We describe a case concerning a 12-year-old girl, diagnosed with a solid pseudopapillary tumour of the pancreas. The symptoms were RAP and postprandial vomiting. The purpose of this article is to increase the knowledge of "alarm findings" indicating an organic disease in children with RAP. PMID:25292323

  2. Radiofrequency ablation of lung tumours

    PubMed Central

    Goh, PYT

    2006-01-01

    Radiofrequency ablation (RFA) is a well-established local therapy for hepatic malignancies. It is rapidly emerging as an effective treatment modality for small lesions elsewhere in the body, in particular, the kidney and the lung. It is a relatively safe and minimally invasive treatment for small lung malignancies, both primary and secondary. In particular, it is the preferred form of treatment for non-surgical candidates. This paper describes the technique employed for radiofrequency ablation of lung tumours, as well as the protocol established, at the Mount Elizabeth Hospital, Singapore. PMID:21614247

  3. A review of bovine urothelial tumours and tumour-like lesions of the urinary bladder.

    PubMed

    Roperto, S; Borzacchiello, G; Brun, R; Leonardi, L; Maiolino, P; Martano, M; Paciello, O; Papparella, S; Restucci, B; Russo, V; Salvatore, G; Urraro, C; Roperto, F

    2010-01-01

    Four hundred bovine urothelial tumours and tumour-like lesions were classified in accordance with the 2004 World Health Organization (WHO) morphological classification for human urothelial tumours. The spectrum of neoplastic lesions of the urinary bladder of cattle is becoming wider and bovine urothelial tumours share striking morphological features with their human counterparts. A classification system based on the WHO scheme would also be appropriate for the classification of bovine bladder tumours. Bovine urothelial tumours are most often multiple. Four distinct growth patterns of bovine urothelial tumours and tumour-like lesions are recognized: flat, exophytic or papillary, endophytic and invasive. Carcinoma in situ (CIS) is the most common flat urothelial lesion, accounting for approximately 4% of urothelial tumours. CIS is detected adjacent to papillary and invasive tumours in 80-90% of cases. Approximately 3% of papillary lesions are papillomas and approximately 5% are 'papillary urothelial neoplasms of low malignant potential' (PUNLMP). Low-grade carcinoma is the most common urothelial tumour of cattle. High-grade carcinomas, and low and high-grade invasive tumours, are less commonly seen. Bovine papillomavirus (BPV) infection and ingestion of bracken fern both play a central role in carcinogenesis of these lesions.

  4. 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

  5. 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

  6. Transillumination imaging of intraocular tumours.

    PubMed

    Kjersem, Bård; Krohn, Jørgen

    2013-06-01

    The purpose of this paper is to discuss a recently described modification of a standard photo slit lamp system for ocular transillumination, with special emphasis on the light transmission through the eye wall and the photographic technique. Transillumination photography was carried out with the Haag-Streit Photo-Slit Lamp BX 900 (Haag-Streit AG, Koeniz, Switzerland). After having released the background lighting optic fibre cable from its holder, the patient was positioned at the slit lamp, and the fibre tip was gently pressed against the sclera or the cornea of the patient's eye. During about 1/1000 of a second, the eye was illuminated by the flash and the scleral shadow of the tumour was exposed to the camera sensor. The images were of good diagnostic quality, making it easy to outline the tumours and to evaluate the involvement of intraocular structures. None of the examined patients experienced discomfort or negative side effects. The method is recommended in cases where photographic transillumination documentation of intraocular pathologies is considered important. PMID:23641762

  7. 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.

  8. 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

  9. 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…

  10. 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…

  11. Pyrosequencing-based methods reveal marked inter-individual differences in oncogene mutation burden in human colorectal tumours

    PubMed Central

    Weidlich, S; Walsh, K; Crowther, D; Burczynski, M E; Feuerstein, G; Carey, F A; Steele, R J C; Wolf, C R; Miele, G; Smith, G

    2011-01-01

    Background: The epidermal growth factor receptor-targeted monoclonal antibody cetuximab (Erbitux) was recently introduced for the treatment of metastatic colorectal cancer. Treatment response is dependent on Kirsten-Ras (K-Ras) mutation status, in which the majority of patients with tumour-specific K-Ras mutations fail to respond to treatment. Mutations in the oncogenes B-Raf and PIK3CA (phosphoinositide-3-kinase) may also influence cetuximab response, highlighting the need for a sensitive, accurate and quantitative assessment of tumour mutation burden. Methods: Mutations in K-Ras, B-Raf and PIK3CA were identified by both dideoxy and quantitative pyrosequencing-based methods in a cohort of unselected colorectal tumours (n=102), and pyrosequencing-based mutation calls correlated with various clinico-pathological parameters. Results: The use of quantitative pyrosequencing-based methods allowed us to report a 13.7% increase in mutation burden, and to identify low-frequency (<30% mutation burden) mutations not routinely detected by dideoxy sequencing. K-Ras and B-Raf mutations were mutually exclusive and independently associated with a more advanced tumour phenotype. Conclusion: Pyrosequencing-based methods facilitate the identification of low-frequency tumour mutations and allow more accurate assessment of tumour mutation burden. Quantitative assessment of mutation burden may permit a more detailed evaluation of the role of specific tumour mutations in the pathogenesis and progression of colorectal cancer and may improve future patient selection for targeted drug therapies. PMID:21712828

  12. The status of epidermal growth factor receptor in borderline ovarian tumours.

    PubMed

    Showeil, Rania; Romano, Claudia; Valganon, Mikel; Lambros, Maryou; Trivedi, Pritesh; Van Noorden, Susan; Sriraksa, Ruethairat; El-Kaffash, Dalal; El-Etreby, Nour; Natrajan, Rachael; Foroni, Letizia; Osborne, Richard; El-Bahrawy, Mona

    2016-03-01

    The majority of borderline ovarian tumours (BOTs) behave in a benign fashion, but some may show aggressive behavior. The reason behind this has not been elucidated. The epidermal growth factor receptor (EGFR) is known to contribute to cell survival signals as well as metastatic potential of some tumours. EGFR expression and gene status have not been thoroughly investigated in BOTs as it has in ovarian carcinomas. In this study we explore protein expression as well as gene mutations and amplifications of EGFR in BOTs in comparison to a subset of other epithelial ovarian tumours. We studied 85 tumours, including 61 BOTs, 10 low grade serous carcinomas (LGSCs), 9 high grade serous carcinomas (HGSCs) and 5 benign epithelial tumours. EGFR protein expression was studied using immunohistochemistry. Mutations were investigated by Sanger sequencing exons 18-21 of the tyrosine kinase domain of EGFR. Cases with comparatively higher protein expression were examined for gene amplification by chromogenic in situ hybridization. We also studied the tumours for KRAS and BRAF mutations. Immunohistochemistry results revealed both cytoplasmic and nuclear EGFR expression with variable degrees between tumours. The level of nuclear localization was relatively higher in BOTs and LGSCs as compared to HGSCs or benign tumours. The degree of nuclear expression of BOTs showed no significant difference from that in LGSCs (mean ranks 36.48, 33.05, respectively, p=0.625), but was significantly higher than in HGSCs (mean ranks: 38.88, 12.61 respectively, p< 0.001) and benign tumours (mean ranks: 35.18, 13.00 respectively, p= 0.010). Cytoplasmic expression level was higher in LGSCs. No EGFR gene mutations or amplification were identified, yet different polymorphisms were detected. Five different types of point mutations in the KRAS gene and the V600E BRAF mutation were detected exclusively in BOTs and LGSCs. Our study reports for the first time nuclear localization of EGFR in BOTs. The nuclear

  13. In vivo electrical conductivity of hepatic tumours.

    PubMed

    Haemmerich, Dieter; Staelin, S T; Tsai, J Z; Tungjitkusolmun, S; Mahvi, D M; Webster, J G

    2003-05-01

    Knowledge of electrical tissue conductivity is necessary to determine deposition of electromagnetic energy and can further be used to diagnostically differentiate between normal and neoplastic tissue. We measured 17 rats with a total of 24 tumours of the K12/TRb rat colon cancer cell line. In each animal we measured in vivo hepatic tumour and normal tissue conductivity at seven frequencies from 10 Hz to 1 MHz, at different tumour stages between 6 and 12 weeks after induction. Conductivity of normal liver tissue was 1.26 +/- 0.15 mS cm(-1) at 10 Hz, and 4.61 +/- 0.42 mS cm(-1) at 1 MHz. Conductivity of tumour was 2.69 +/- 0.91 mS cm(-1) at 10 Hz, and 5.23 +/- 0.82 mS cm(-1) at 1 MHz. Conductivity was significantly different between normal and tumour tissue (p < 0.05). We determined the percentage of necrosis and fibrosis at the measurement site. We fitted the conductivity data to the Cole-Cole model. For the tumour data we determined Spearman's correlation coefficients between the Cole-Cole parameters and age, necrosis, fibrosis and tumour volume and found significant correlation between necrosis and the Cole-Cole parameters (p < 0.05). We conclude that necrosis within the tumour and the associated membrane breakdown is likely responsible for the observed change in conductivity.

  14. Cartilage-containing tumours of the lung

    PubMed Central

    Bateson, Eric M.

    1967-01-01

    An unusual case is reported of a woman aged 27 years who presented with four intrapulmonary cartilage-containing tumours which were resected from the left lung. The appearance of two new shadows in the chest several years later suggested that two of the resected tumours had recurred. Three of the four resected tumours consisted entirely of cartilage and bone and other connective tissues. The fourth tumour, although consisting almost entirely of cartilage and connective tissue, also contained epithelial tissue in the form of two small clefts, one in the periphery and the other in a connective tissue septum between the lobules of cartilage of the tumour. These tumours are regarded as a variation of the more typical cartilage-containing tumour of the lung which contains many spaces lined by respiratory epithelium and is regarded as a neoplasm arising in the connective tissue beneath the mucosa of a small bronchus with subsequent expansion into its lumen and enclosing spaces lined by the mucosal epithelium during its eccentric growth. The tumours consisting almost entirely of cartilage without spaces lined by epithelial cells are thought to expand into the adjacent lung tissue and not into the bronchial lumen. Therefore there is no inclusion of respiratory epithelium from the mucosa of the bronchus of origin. Images PMID:6033393

  15. FDG uptake, a surrogate of tumour hypoxia?

    PubMed Central

    Van de Wiele, Christophe

    2008-01-01

    Introduction Tumour hyperglycolysis is driven by activation of hypoxia-inducible factor-1 (HIF-1) through tumour hypoxia. Accordingly, the degree of 2-fluro-2-deoxy-d-glucose (FDG) uptake by tumours might indirectly reflect the level of hypoxia, obviating the need for more specific radiopharmaceuticals for hypoxia imaging. Discussion In this paper, available data on the relationship between hypoxia and FDG uptake by tumour tissue in vitro and in vivo are reviewed. In pre-clinical in vitro studies, acute hypoxia was consistently shown to increase FDG uptake by normal and tumour cells within a couple of hours after onset with mobilisation or modification of glucose transporters optimising glucose uptake, followed by a delayed response with increased rates of transcription of GLUT mRNA. In pre-clinical imaging studies on chronic hypoxia that compared FDG uptake by tumours grown in rat or mice to uptake by FMISO, the pattern of normoxic and hypoxic regions within the human tumour xenografts, as imaged by FMISO, largely correlated with glucose metabolism although minor locoregional differences could not be excluded. In the clinical setting, data are limited and discordant. Conclusion Further evaluation of FDG uptake by various tumour types in relation to intrinsic and bioreductive markers of hypoxia and response to radiotherapy or hypoxia-dependent drugs is needed to fully assess its application as a marker of hypoxia in the clinical setting. PMID:18509637

  16. CT/MRI of neuroendocrine tumours

    PubMed Central

    Reznek, Rodney H

    2006-01-01

    Neuroendocrine tumours (NETs) are often thought to be rare and rather recherché cancers which are of little concern to the general physician, surgeon or radiologist because of their rarity and esoteric nature. In fact, while relatively uncommon, the total group of gastro-entero-pancreatic (GEP) tumours incorporates the spectrum of all types of carcinoids, incuding bronchial carcinoids, and the whole gamut of islet-cell tumours. Some of these may present as functioning tumours, with a plethora of hormonal secretions and concomitant clinical syndromes, and GEPs in general have an incidence around 30 per million population per year. This means that in the whole European Union, for example, there will be in the region of 12000 new patients every year presenting with one or another manifestation of these tumours. Furthermore, the comparatively long survival of many of these patients, compared to more common adenocarcinomas or epithelial tumours, implies that the point prevalence is also not inconsiderable. However, it is undoubtedly true that these tumours can be difficult to identify, especially in their early stages, and it is then that radiological investigation becomes of paramount importance. Having taken into account all these considerations, most investigators would initiate investigation of a suspected or biochemically proven islet-cell tumour with cross-sectional imaging—either CT or MRI. This will clearly identify the larger lesions, allow assessment of the entire abdomen, and provide valuable information on the presence of hepatic metastates. PMID:17114072

  17. Küttner's tumour: a case report.

    PubMed

    Tagnon, B; Weynand, B; Reychler, H

    2008-01-01

    Küttner's tumour (chronic sclerosing sialadenitis) is a chronic inflammatory disease of the salivary glands. It is a totally benign lesion. However, because of its clinical features, the clinical diagnosis is often that of a salivary gland neoplasm. We present a case of unilateral Küttner's tumour in the left submandibular salivary gland and discuss clinical, imaging and histological features.

  18. SDH mutations in tumorigenesis and inherited endocrine tumours: lesson from the phaeochromocytoma-paraganglioma syndromes.

    PubMed

    Pasini, B; Stratakis, C A

    2009-07-01

    A genetic predisposition for paragangliomas and adrenal or extra-adrenal phaeochromocytomas was recognized years ago. Beside the well-known syndromes associated with an increased risk of adrenal phaeochromocytoma, Von Hippel Lindau disease, multiple endocrine neoplasia type 2 and neurofibromatosis type 1, the study of inherited predisposition to head and neck paragangliomas led to the discovery of the novel 'paraganglioma-phaeochromocytoma syndrome' caused by germline mutations in three genes encoding subunits of the succinate dehydrogenase (SDH) enzyme (SDHB, SDHC and SDHD) thus opening an unexpected connection between mitochondrial tumour suppressor genes and neural crest-derived cancers. Germline mutations in SDH genes are responsible for 6% and 9% of sporadic paragangliomas and phaeochromocytomas, respectively, 29% of paediatric cases, 38% of malignant tumours and more than 80% of familial aggregations of paraganglioma and phaeochromocytoma. The disease is characterized by autosomal dominant inheritance with a peculiar parent-of-origin effect for SDHD mutations. Life-time tumour risk seems higher than 70% with variable clinical manifestantions depending on the mutated gene. In this review we summarize the most recent knowledge about the role of SDH deficiency in tumorigenesis, the spectrum and prevalence of SDH mutations derived from several series of cases, the related clinical manifestantions including rare phenotypes, such as the association of paragangliomas with gastrointestinal stromal tumours and kidney cancers, and the biological hypotheses attempting to explain genotype to phenotype correlation. PMID:19522823

  19. Strain elastography features of epidermoid tumours in superficial soft tissue: differences from other benign soft-tissue tumours and malignant tumours

    PubMed Central

    Park, H J; Lee, S M; Kim, W T; Lee, S; Ahn, K S

    2015-01-01

    Objective: We evaluated ultrasonographic features of superficial epidermoid tumour with a focus on strain elastography (SE) features that will help in the differential diagnosis of epidermoid tumour from other benign and malignant soft-tissue tumours. Methods: We retrospectively evaluated ultrasonographic and SE data of 103 surgically confirmed superficial soft-tissue tumours and tumour-like lesions: 29 cases of epidermoid tumour, 46 cases of other benign tumours and 28 cases of malignant tumour. SE and B-mode imaging were performed at the same time. SE characteristics were assigned into four grades (1–4) according to their elasticity. Interobserver agreement for the four SE scores between the two radiologists was analysed using kappa statistics. We classified each SE finding as a hard lesion (SE Score 3–4) or soft lesion (SE Score 1–2) and compared these findings using the χ2 test to identify whether a significant difference in mass hardness existed among epidermoid tumour, other benign tumour and malignant tumour. Results: Overall interobserver agreement according to the four SE scores was moderate (κ = 0.540), and overall agreement for the hardness [soft (Score 1–2) or hard (Score 3–4)] was almost perfect (κ = 0.825). Malignant tumours showed higher SE scores (3–4, hard nature) than did epidermoid tumour or other benign soft-tissue tumours. There were no differences in SE score between epidermoid tumour and other benign tumours. Conclusion: Superficial epidermoid tumour exhibits a softer nature than does malignant tumour but does not have a different SE pattern from other benign tumours. Advances in knowledge: SE features of epidermoid tumour might be helpful in differentiating from other benign and malignant tumours. PMID:25827206

  20. Optimization of tumour control probability in hypoxic tumours by radiation dose redistribution: a modelling study.

    PubMed

    Søvik, Aste; Malinen, Eirik; Bruland, Øyvind S; Bentzen, Søren M; Olsen, Dag Rune

    2007-01-21

    Tumour hypoxia is a known cause of clinical resistance to radiation therapy. The purpose of this work was to model the effects on tumour control probability (TCP) of selectively boosting the dose to hypoxic regions in a tumour, while keeping the mean tumour dose constant. A tumour model with a continuous oxygen distribution, incorporating pO(2) histograms published for head and neck patients, was developed. Temporal and spatial variations in the oxygen distribution, non-uniform cell density and cell proliferation during treatment were included in the tumour modelling. Non-uniform dose prescriptions were made based on a segmentation of the tumours into four compartments. The main findings were: (1) Dose redistribution considerably improved TCP for all tumours. (2) The effect on TCP depended on the degree of reoxygenation during treatment, with a maximum relative increase in TCP for tumours with poor or no reoxygenation. (3) Acute hypoxia reduced TCP moderately, while underdosing chronic hypoxic cells gave large reductions in TCP. (4) Restricted dose redistribution still gave a substantial increase in TCP as compared to uniform dose boosts. In conclusion, redistributing dose according to tumour oxygenation status might increase TCP when the tumour response to radiotherapy is limited by chronic hypoxia. This could potentially improve treatment outcome in a subpopulation of patients who respond poorly to conventional radiotherapy. PMID:17202629

  1. p53 tumour suppressor gene expression in pancreatic neuroendocrine tumour cells.

    PubMed Central

    Bartz, C; Ziske, C; Wiedenmann, B; Moelling, K

    1996-01-01

    Neuroendocrine pancreatic tumours grow slower and metastasise later than ductal and acinar carcinomas. The expression of the p53 tumour suppressor gene in pancreatic neuroendocrine tumour cells is unknown. Pancreatic neuroendocrine cell lines (n = 5) and human tumour tissues (n = 19) were studied for changed p53 coding sequence, transcription, and translation. Proliferative activity of tumour cells was determined analysing Ki-67 expression. No mutation in the p53 nucleotide sequence of neuroendocrine tumour cell was found. However, an overexpression of p53 could be detected in neuroendocrine pancreatic tumour cell lines at a protein level. As no p53 mutations were seen, it is suggested that post-translational events can also lead to an overexpression of p53. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8675094

  2. 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…

  3. Solitary fibrous tumour of the renal peripelvis.

    PubMed

    Fukunaga, M; Nikaido, T

    1997-05-01

    Solitary fibrous tumours (SFTs) are rare spindle cell neoplasms generally associated with the serosal surface, especially the pleura. This report describes two SFTs arising in the renal peripelvis, occurring in 33- and 36-year-old females. The lesions lacked the characteristic features of other recognized neoplasms that occur in the kidney. Immunohistochemically, the tumour cells were diffusely and strongly positive for vimentin and CD34, and some tumour cells expressed alpha-smooth muscle actin. Both tumours were diploid by flow cytometry. Both patients have had benign clinical courses with 7.5- and 1-year follow-up. The findings suggest that the SFTs may originate from peripelvic mesenchymal cells, a new location for SFT. SFT should be included in the differential diagnosis of spindle cell tumours arising in the renal pelvis and peripelvis.

  4. Semi-supervised analysis of human brain tumours from partially labeled MRS information, using manifold learning models.

    PubMed

    Cruz-Barbosa, Raúl; Vellido, Alfredo

    2011-02-01

    Medical diagnosis can often be understood as a classification problem. In oncology, this typically involves differentiating between tumour types and grades, or some type of discrete outcome prediction. From the viewpoint of computer-based medical decision support, this classification requires the availability of accurate diagnoses of past cases as training target examples. The availability of such labeled databases is scarce in most areas of oncology, and especially so in neuro-oncology. In such context, semi-supervised learning oriented towards classification can be a sensible data modeling choice. In this study, semi-supervised variants of Generative Topographic Mapping, a model of the manifold learning family, are applied to two neuro-oncology problems: the diagnostic discrimination between different brain tumour pathologies, and the prediction of outcomes for a specific type of aggressive brain tumours. Their performance compared favorably with those of the alternative Laplacian Eigenmaps and Semi-Supervised SVM for Manifold Learning models in most of the experiments.

  5. Histologically malignant solitary fibrous tumour of the anterior thoracic wall: a case report and review of the literature.

    PubMed

    Archontaki, Maria; Korkolis, Dimitris P; Arnogiannaki, Niki; Hatzijiannis, Stelios; Dendrinos, Panagiotis; Megapanos, Christos; Kassotakis, Dimitris; Kokkalis, Georgios

    2010-01-01

    Solitary fibrous tumour (SFT) is a rare oncological entity that most often arises in the pleura. Over the past 10 years, the tumour has been described at numerous extrapleural locations. We present the case of a 42-year-old female Caucasian patient with an extrapleural SFT located at the anterior thoracic wall for 22 years, with atypical histological characteristics and clinical features of malignancy. Management consisted of a wide surgical resection, plastic reconstruction, and postoperative radiotherapy. Although extrapleural SFT usually behaves as a benign soft tissue tumour, it can also present with a more aggressive local behavior, including locoregional recurrence or metastasis. In that case, a multidisciplinary approach is required for accurate diagnosis and proper management.

  6. MET is required for the recruitment of anti-tumoural neutrophils

    PubMed Central

    Finisguerra, Veronica; Di Conza, Giusy; Di Matteo, Mario; Serneels, Jens; Costa, Sandra; Thompson, A.A. Roger; Wauters, Els; Walmsley, Sarah; Prenen, Hans; Granot, Zvi; Casazza, Andrea; Mazzone, Massimiliano

    2015-01-01

    Mutations or amplification of the MET proto-oncogene are involved in the pathogenesis of several tumours1-4, which rely on the constitutive engagement of this pathway for their growth and survival1,5. However, MET is expressed not only by cancer cells but also by tumour-associated stromal cells although its precise role in this compartment is not well characterized6-11. Here, we show that MET is required for neutrophil chemoattraction and cytotoxicity in response to its ligand HGF. Met deletion in neutrophils enhances tumour growth and metastasis. This phenotype correlates with reduced neutrophil infiltration to both primary tumour and metastatic site. Similarly, Met is necessary for neutrophil transudation during colitis, skin rash or peritonitis. Mechanistically, Met is induced by tumour-derived TNF-α or other inflammatory stimuli in both mouse and human neutrophils. This induction is instrumental for neutrophil transmigration across an activated endothelium and iNOS production upon HGF stimulation. Consequently, HGF/MET-dependent nitric oxide release by neutrophils promotes cancer cell killing, which abates tumour growth and metastasis. Following systemic administration of a MET kinase inhibitor, we prove that the therapeutic benefit of MET targeting in cancer cells is partly countered by the pro-tumoural effect rising from MET blockade in neutrophils. Our work identifies an unprecedented role of MET in neutrophils, suggests a potential “Achilles’ heel” of MET-targeted therapies in cancer, and supports the rationale for evaluating anti-MET drugs in certain inflammatory diseases. PMID:25985180

  7. Expression of beta2 integrins and macrophage-associated antigens in meningeal tumours.

    PubMed

    Mosnier, J F; Perret, A G; Scoazec, J Y; Brunon, J

    2000-02-01

    This study assessed the expression of leukocyte integrins and macrophage-associated antigens in meningiomas. Fourteen benign meningiomas, ten atypical/anaplastic meningiomas, two hemangiopericytomas and one solitary fibrous tumour (SFT) were included. Frozen sections were immunostained using antibodies directed against leukocyte integrins, CD68, CD14, CD2, CD1a, DRC1 and CD34. Their expression was evaluated semi-quantitatively. Ki67 positive cells were counted. Arachnoid membranes served as controls. Arachnoid cells expressed the beta2-integrin subunit and KP1. Beta2 was detected in the tumour cells of 14 meningiomas. In nine cases, this was associated with an alpha-integrin subunit. There was no statistical difference in the expression of beta2 between benign and atypical/anaplastic meningiomas. KP1 was constantly expressed by the tumour cells of meningiomas. It was not expressed by other meningeal tumours. CD34 was detected in the fibrous meningiomas, hemangiopericytomas and the SFT. In each tumour, macrophages were more numerous than T lymphocytes. There was no statistical difference in the density of macrophages and T lymphocytes between the benign and atypical/anaplastic meningiomas. There was no correlation between the Ki67 proliferation index and macrophage infiltration. Meningiomas, through the expression of leukocyte antigens, have a very particular phenotype. The expression of beta2 integrins could play a role in the attraction of immunocompetent cells in the stroma of meningiomas.

  8. Analysis of CC chemokine and chemokine receptor expression in solid ovarian tumours

    PubMed Central

    Scotton, C; Milliken, D; Wilson, J; Raju, S; Balkwill, F

    2001-01-01

    To understand the chemokine network in a tissue, both chemokine and chemokine receptor expression should be studied. Human epithelial ovarian tumours express a range of chemokines but little is known about the expression and localisation of chemokine receptors. With the aim of understanding chemokine action in this cancer, we investigated receptors for CC–chemokines and their ligands in 25 biopsies of human ovarian cancer. CC–chemokine receptor mRNA was generally absent from solid tumours, the exception being CCR1 which was detected in samples from 75% of patients. CCR1 mRNA localised to macrophages and lymphocytes and there was a correlation between numbers of CD8+ and CCR1 expressing cells (P = 0.031). mRNA for 6 CC-chemokines was expressed in a majority of tumour samples. In a monocytic cell line in vitro, we found that CCR1 mRNA expression was increased 5-fold by hypoxia. We suggest that the CC-chemokine network in ovarian cancer is controlled at the level of CC-chemokine receptors and this may account for the phenotypes of infiltrating cells found in these tumours. The leukocyte infiltrate may contribute to tumour growth and spread by providing growth survival factors and matrix metalloproteases. Thus, CCR1 may be a novel therapeutic target in ovarian cancer. http://www.bjcancer.com © 2001 Cancer Research Campaignhttp://www.bjcancer.com PMID:11556842

  9. Beneficial role of overexpression of TFPI-2 on tumour progression in human small cell lung cancer☆

    PubMed Central

    Lavergne, Marion; Jourdan, Marie-Lise; Blechet, Claire; Guyetant, Serge; Pape, Alain Le; Heuze-Vourc’h, Nathalie; Courty, Yves; Lerondel, Stephanie; Sobilo, Julien; Iochmann, Sophie; Reverdiau, Pascale

    2013-01-01

    Tissue factor pathway inhibitor-2 (TFPI-2) is a potent inhibitor of plasmin, a protease which is involved in tumour progression by activating (MMPs). This therefore makes TFPI-2 a potential inhibitor of invasiveness and the development of metastases. In this study, low levels of TFPI-2 expression were found in 65% of patients with small cell lung cancer (SCLC), the most aggressive type of lung cancer. To study the impact of TFPI-2 in tumour progression, TFPI-2 was overexpressed in NCI-H209 SCLC cells which were orthotopically implanted in nude mice. Investigations showed that TFPI-2 inhibited lung tumour growth. Such inhibition could be explained in vitro by a decrease in tumour cell viability, blockade of G1/S phase cell cycle transition and an increase in apoptosis shown in NCI-H209 cells expressing TFPI-2. We also demonstrated that TFPI-2 upregulation in NCI-H209 cells decreased MMP expression, particularly by downregulating MMP-1 and MMP-3. Moreover, TFPI-2 inhibited phosphorylation of the MAPK signalling pathway proteins involved in the induction of MMP transcripts, among which MMP-1 was predominant in SCLC tissues and was inversely expressed with TFPI-2 in 35% of cases. These results suggest that downregulation of TFPI-2 expression could favour the development of SCLC. PMID:23905012

  10. Denosumab and giant cell tumour of bone—a review and future management considerations

    PubMed Central

    Xu, S.F.; Adams, B.; Yu, X.C.; Xu, M.

    2013-01-01

    Giant cell tumour of bone (gctb) is one type of giant-cell-rich bone lesion characterized by the presence of numerous multinucleated osteoclast-type giant cells. Giant cells are known to express rankl (receptor activator of nuclear factor κB ligand) and are responsible for the aggressive osteolytic nature of the tumour. No available treatment option is definitively effective in curing this disease, especially in surgically unsalvageable cases. In recent years, several studies of denosumab in patients with advanced or unresectable gctb have shown objective changes in tumour composition, reduced bony destruction, and clinical benefit. Denosumab is a fully human monoclonal antibody that targets and binds with high affinity and specificity to rankl. Several large phase iii studies have shown that denosumab is more effective than bisphosphonates in reducing skeletal morbidity arising from a wide range of tumours and that it can delay bone metastasis. The relevant articles are reviewed here. The controversies related to the future use of denosumab in the treatment of gctb are discussed. PMID:24155640

  11. Selective targeting of tumour neovasculature by a radiohalogenated human antibody fragment specific for the ED-B domain of fibronectin.

    PubMed

    Demartis, S; Tarli, L; Borsi, L; Zardi, L; Neri, D

    2001-04-01

    Angiogenesis is a characteristic feature of many aggressive tumours and other disorders. Antibodies capable of binding to new blood vessels, but not to mature vessels, could be used as selective targeting agents for immunoscintigraphic and radioimmunotherapeutic applications. Here we show that scFv(L19), a recombinant human antibody fragment with sub-nanomolar affinity for the ED-B domain of fibronectin, a marker of angiogenesis, can be stably labelled with iodine-125 and astatine-211 with full retention of immunoreactivity, using a trimethyl-stannyl benzoate bifunctional derivative. Biodistribution studies in mice bearing two different types of tumour grafted subcutaneously, followed by ex vivo micro-autoradiographic analysis, revealed that scFv(L19) rapidly localises around tumour blood vessels, but not around normal vessels. Four hours after intravenous injection of the stably radioiodinated scFv(L19), tumour to blood ratios were 6:1 in mice bearing the F9 murine teratocarcinoma and 9:1 in mice bearing an FE8 rat sarcoma. As expected, all other organs (including kidney) contained significantly less radioactivity than the tumour. Since the ED-B domain of fibronectin has an identical sequence in mouse and man, scFv(L19) is a pan-species antibody and the results presented here suggest clinical utility of radiolabelled scFv(L19) for the scintigraphic detection of angiogenesis in vivo. Furthermore, it should now be possible to investigate scFv(L19) for the selective delivery of 211At to the tumour neovasculature, causing the selective death of tumour endothelial cells and tumour collapse. PMID:11357506

  12. Relationship between tumour shrinkage and reduction in Ki67 expression after primary chemotherapy in human breast cancer

    PubMed Central

    Bottini, A; Berruti, A; Bersiga, A; Brizzi, M P; Bruzzi, P; Aguggini, S; Brunelli, A; Bolsi, G; Allevi, G; Generali, D; Betri, E; Bertoli, G; Alquati, P; Dogliotti, L

    2001-01-01

    The association between tumour shrinkage and reduction in kinetic cell activity after primary chemotherapy in human breast cancer is still a matter of investigation. 157 patients with T2-4, N0-1, M0 breast cancer received primary chemotherapy consisting of either the CMF regimen + tamoxifen (the first consecutive 76 cases) or the single agent epirubicin (the subsequent 81). Ki67, p53, bcl2, c-erbB2 and steroid hormone receptors were evaluated immunohistochemically in tumour specimens obtained before chemotherapy and at surgery. Tumour shrinkage of >50% occurred in 72.4% of patients. Ki67 expression significantly decreased after chemotherapy; the reduction correlated with tumour response in both univariate (P < 0.005) and multivariate analysis (P = 0.02). p53, bcl-2, steroid hormone receptor and c-erbB2 immunostaining were scarcely affected. Baseline bcl2 (P = 0.04) and c-erbB2 (P = 0.02) were directly and inversely associated with the reduction in Ki67 immunostaining, respectively. Baseline p53 expression (P < 0.01) was directly related with Ki67 expression at residual tumour, whereas oestrogen receptor expression (P < 0.001) was inversely related. Ki67 at residual tumour was a better predictor for relapse-free survival (RFS) than baseline Ki67. Clinical response (P < 0.03), but not reduction in Ki67, was a significant independent predictor for disease recurrence. Chemotherapy was found to induce tumour shrinkage and to reduce the number of cells in the cell cycle, but its effect on tumour biology/aggressiveness was minimal. Reduction in Ki67 immunostaining correlated with clinical response but failed to be related to RFS. Ki67 expression at surgery rather than at baseline appears to be a better predictor for disease relapse. © 2001 Cancer Research Campaign  http://www.bjcancer.com PMID:11710821

  13. Characterization of HOX gene expression in canine mammary tumour cell lines from spontaneous tumours.

    PubMed

    DeInnocentes, P; Perry, A L; Graff, E C; Lutful Kabir, F M; Curtis Bird, R

    2015-09-01

    Spatial/temporal controls of development are regulated by the homeotic (HOX) gene complex and require integration with oncogenes and tumour suppressors regulating cell cycle exit. Spontaneously derived neoplastic canine mammary carcinoma cell models were investigated to determine if HOX expression profiles were associated with neoplasia as HOX genes promote neoplastic potential in human cancers. Comparative assessment of human and canine breast cancer expression profiles revealed remarkable similarity for all four paralogous HOX gene clusters and several unlinked HOX genes. Five canine HOX genes were overexpressed with expression profiles consistent with oncogene-like character (HOXA1, HOXA13, HOXD4, HOXD9 and SIX1) and three HOX genes with underexpressed profiles (HOXA11, HOXC8 and HOXC9) were also identified as was an apparent nonsense mutation in HOXC6. This data, as well as a comparative analysis of similar data from human breast cancers suggested expression of selected HOX genes in canine mammary carcinoma could be contributing to the neoplastic phenotype. PMID:24034269

  14. Characterization of HOX gene expression in canine mammary tumour cell lines from spontaneous tumours.

    PubMed

    DeInnocentes, P; Perry, A L; Graff, E C; Lutful Kabir, F M; Curtis Bird, R

    2015-09-01

    Spatial/temporal controls of development are regulated by the homeotic (HOX) gene complex and require integration with oncogenes and tumour suppressors regulating cell cycle exit. Spontaneously derived neoplastic canine mammary carcinoma cell models were investigated to determine if HOX expression profiles were associated with neoplasia as HOX genes promote neoplastic potential in human cancers. Comparative assessment of human and canine breast cancer expression profiles revealed remarkable similarity for all four paralogous HOX gene clusters and several unlinked HOX genes. Five canine HOX genes were overexpressed with expression profiles consistent with oncogene-like character (HOXA1, HOXA13, HOXD4, HOXD9 and SIX1) and three HOX genes with underexpressed profiles (HOXA11, HOXC8 and HOXC9) were also identified as was an apparent nonsense mutation in HOXC6. This data, as well as a comparative analysis of similar data from human breast cancers suggested expression of selected HOX genes in canine mammary carcinoma could be contributing to the neoplastic phenotype.

  15. Neuroendocrine tumours - Medical therapy: Biological.

    PubMed

    Rinke, Anja; Krug, Sebastian

    2016-01-01

    Somatostatin analogues (SSA) are well established antisecretory drugs that have been used as first line treatment for symptomatic control in hormonally active neuroendocrine tumours (NET) for three decades. Both available depot formulations of SSA, long-acting repeatable (LAR) octreotide and lanreotide autogel, seem similarly effective and well tolerated, although comparative trials in NET have not been performed. The importance of SSA as antiproliferative treatment has been increasingly recognized during recent years. Two placebo-controlled trials demonstrated significant prolongation of progression free survival under SSA treatment. However, objective response as assessed by imaging is rare. Interferon-α (IFNα) also has antisecretory and antiproliferative efficacy in NET. Due to the less favourable toxicity profile it mainly has a role as add-on option in the refractory setting, especially in carcinoid syndrome patients. Further studies are needed to evaluate the antiproliferative efficacy of the multiligand SSA pasireotide and the role of pegylated IFNα. PMID:26971845

  16. Molecular genetic analysis of flow-sorted ovarian tumour cells: improved detection of loss of heterozygosity.

    PubMed Central

    Abeln, E. C.; Corver, W. E.; Kuipers-Dijkshoorn, N. J.; Fleuren, G. J.; Cornelisse, C. J.

    1994-01-01

    Detection of loss of heterozygosity (LOH) is usually performed on homogenised tumour specimens. In this type of analysis samples with a low percentage of tumour cells have to be excluded and possible intra-tumour heterogeneity is obscured. In this study we report the application of polymerase chain reaction (PCR)-driven LOH detection with in total 22 microsatellite markers for chromosome 1q, 3p, 3q, 4p, 6p, 6q, 11p, 11q, 17p, 17q, 18p, 18q, Xp and Xq on flow-sorted cells from fresh and paraffin-embedded ovarian tumour tissue. Titration experiments showed that LOH can be detected with as few as 100 cell equivalents of DNA. Clear examples of LOH could be detected in the sorted aneuploid fractions from one unilateral and two bilateral ovarian tumours from three patients. In two samples the sorted fraction was less than 10% of the total sample. The bilateral tumours from the same patient showed loss of identical alleles for one marker (case OV64) and two markers (case OV69), indicative of their monoclonal origin. Multiparameter flow cytometry using two different ovarian tumour markers (MOv18 and BMA180), an anti-cytokeratin monoclonal antibody (MAb) (M9), an anti-vimentin MAb (V9) and a MAb against the panepithelial antigen 17-1A on the fresh ascites cells of the fourth ovarian cancer patient was used to investigate possible intra-tumour heterogeneity. We showed the presence of at least three phenotypically different populations, of which the diploid, keratin-positive, vimentin-negative population showed a similar LOH pattern as the aneuploid population (DNA index = 1.7), indicative of its neoplastic origin. The same LOH pattern was shown in an omentum metastasis from this patient also having the same aneuploid DNA index of 1.7. The sharing of the same LOH pattern by the diploid and aneuploid tumour cell populations suggests that the observed allele loss events occurred before the development of aneuploidy. PCR on flow-sorted cells is thus an important tool to study

  17. A surface acoustic wave biosensor for interrogation of single tumour cells in microcavities.

    PubMed

    Senveli, Sukru U; Ao, Zheng; Rawal, Siddarth; Datar, Ram H; Cote, Richard J; Tigli, Onur

    2016-01-01

    In this study, biological cells are sensed and characterized with surface acoustic wave (SAW) devices utilising microcavities. After tumour cells in media are transported to and trapped in microcavities, the proposed platform uses SAW interaction between the substrate and the cells to extract their mechanical stiffness based on the ultrasound velocity. Finite element method (FEM) analysis and experimental results show that output phase information is an indicator of the stiffness modulus of the trapped cells. Small populations of various types of cells such as MCF7, MDA-MB-231, SKBR3, and JJ012 were characterized and characteristic moduli were estimated for each cell population. Results show that high frequency stiffness modulus is a possible biomarker for aggressiveness of the tumour and that microcavity coupled SAW devices are a good candidate for non-invasive interrogation of single cells.

  18. The proliferation marker Chromatin Assembly Factor-1 is of clinical value in predicting the biological behaviour of salivary gland tumours.

    PubMed

    Staibano, Stefania; Mascolo, Massimo; Rocco, Alba; Lo Muzio, Lorenzo; Ilardi, Gennaro; Siano, Maria; Pannone, Giuseppe; Vecchione, Maria Luisa; Nugnes, Loredana; Califano, Luigi; Zamparese, Rosanna; Bufo, Pantaleo; De Rosa, Gaetano

    2011-01-01

    Salivary gland tumours (SGT) constitute a diagnostically challenging group of neoplasms with frequently unpredictable clinical outcome. The proliferation rate facilitates the identification of aggressive SGT. The Chromatin Assembly Factor-1 (CAF-1) is a major epigenetic regulator of nuclear chromatin organization during DNA replication. It plays a critical function in human tumourigenesis and has been proposed as a new proliferation and prognostic marker for some malignancies. This study focused on the role of CAF-1/p60 protein as a marker of clinical value for SGT. The expression of CAF-1/p60 was evaluated by immunohistochemistry on a retrospective series of 362 surgically excised benign and malignant SGT with different histogenesis and, when available, on fine-needle pre-surgical cytological biopsies. The resulting data were compared with traditional prognostic parameters, including the expression of the routine proliferation marker ki67/MIB1. CAF-1/p60 was detectable in all SGT, with highest degree of expression in metastasizing malignant tumours. Moreover, the cases of benign tumours which progressed to carcinoma during the follow-up, showed significantly higher CAF-1/p60 expression than non-progressing benign SGT, both on histological sections and cytological smears of the primary tumour. Cox's multiple regression analysis selected CAF-1/p60 expression as the best independent predictor of cancer development for benign SGT (p<0.0001), and the best independent predictor of metastasis onset for malignant tumours (p<0.0004). Overexpression of CAF-1/p60, on histological and/or cytological samples, characterizes malignant SGT with aggressive behaviour, irrespective of their specific histotype, and allows the early diagnosis of progression toward malignancy of morphologically benign tumours.

  19. Transsphenoidal surgery for pituitary tumours

    PubMed Central

    Massoud, A; Powell, M; Williams, R; Hindmarsh, P; Brook, C

    1997-01-01

    Accepted 29 January 1997
 OBJECTIVES—Transsphenoidal surgery (TSS) is the preferred method for the excision of pituitary microadenomas in adults. This study was carried out to establish the long term efficacy and safety of TSS in children.
STUDY DESIGN—A 14 year retrospective analysis was carried out on 23 children (16 boys and seven girls), all less than 18 years of age, who had undergone TSS at our centre.
RESULTS—Twenty nine transsphenoidal surgical procedures were carried out. The most common diagnosis was an adrenocorticotrophic hormone (ACTH) secreting adenoma (14 (61%) patients). The median length of follow up was 8.0 years (range 0.3-14.0 years). Eighteen (78%) patients were cured after the first procedure. No death was related to the operation. The most common postoperative complication was diabetes insipidus, which was transient in most patients. Other complications were headaches in two patients and cerebrospinal fluid leaks in two patients. De novo endocrine deficiencies after TSS in children were as follows: three (14%) patients developed panhypopituitarism, eight (73%) developed growth hormone insufficiency, three (14%) developed secondary hypothyroidism, and four (21%) developed gonadotrophin deficiency. Permanent ACTH deficiency occurred in five (24%) patients, though all patients received postoperative glucocorticoid treatment until dynamic pituitary tests were performed three months after TSS.
CONCLUSIONS—TSS in children is a safe and effective treatment for pituitary tumours, provided it is performed by surgeons with considerable experience and expertise. Surgical complications are minimal. Postoperative endocrine deficit is considerable, but is only permanent in a small proportion of patients.

 • Transsphenoidal surgery is a safe and effective treatment for pituitary tumours in children • Transsphenoidal surgery should be performed by surgeons with considerable experience and expertise • Surgical complications of

  20. Solitary fibrous tumour of the pancreas: a new member of the small group of mesenchymal pancreatic tumours.

    PubMed

    Lüttges, J; Mentzel, T; Hübner, G; Klöppel, G

    1999-07-01

    Solitary fibrous tumours usually occur in the pleura, but occasionally they appear in extraserosal soft tissues or parenchymatous organs, where their diagnosis often causes problems. This report describes a solitary fibrous tumour (SFT) of the pancreas in a 50-year-old woman treated by left-side pancreatectomy. The tumour showed immunocytochemical reactivity for CD34, CD99 and bcl-2. Because of its favourable prognosis, SFT must be clearly distinguished from leiomyosarcoma, the most frequent nonepithelial tumour of the pancreas. Other mesenchymal tumours that may occur in the pancreas include tumours of the peripheral nerve sheath, fibrous histiocytic tumours and rare vascular tumours.

  1. Functional polarization of tumour-associated macrophages by tumour-derived lactic acid.

    PubMed

    Colegio, Oscar R; Chu, Ngoc-Quynh; Szabo, Alison L; Chu, Thach; Rhebergen, Anne Marie; Jairam, Vikram; Cyrus, Nika; Brokowski, Carolyn E; Eisenbarth, Stephanie C; Phillips, Gillian M; Cline, Gary W; Phillips, Andrew J; Medzhitov, Ruslan

    2014-09-25

    Macrophages have an important role in the maintenance of tissue homeostasis. To perform this function, macrophages must have the capacity to monitor the functional states of their 'client cells': namely, the parenchymal cells in the various tissues in which macrophages reside. Tumours exhibit many features of abnormally developed organs, including tissue architecture and cellular composition. Similarly to macrophages in normal tissues and organs, macrophages in tumours (tumour-associated macrophages) perform some key homeostatic functions that allow tumour maintenance and growth. However, the signals involved in communication between tumours and macrophages are poorly defined. Here we show that lactic acid produced by tumour cells, as a by-product of aerobic or anaerobic glycolysis, has a critical function in signalling, through inducing the expression of vascular endothelial growth factor and the M2-like polarization of tumour-associated macrophages. Furthermore, we demonstrate that this effect of lactic acid is mediated by hypoxia-inducible factor 1α (HIF1α). Finally, we show that the lactate-induced expression of arginase 1 by macrophages has an important role in tumour growth. Collectively, these findings identify a mechanism of communication between macrophages and their client cells, including tumour cells. This communication most probably evolved to promote homeostasis in normal tissues but can also be engaged in tumours to promote their growth.

  2. Paediatric extracranial germ-cell tumours.

    PubMed

    Shaikh, Furqan; Murray, Matthew J; Amatruda, James F; Coleman, Nicholas; Nicholson, James C; Hale, Juliet P; Pashankar, Farzana; Stoneham, Sara J; Poynter, Jenny N; Olson, Thomas A; Billmire, Deborah F; Stark, Daniel; Rodriguez-Galindo, Carlos; Frazier, A Lindsay

    2016-04-01

    Management of paediatric extracranial germ-cell tumours carries a unique set of challenges. Germ-cell tumours are a heterogeneous group of neoplasms that present across a wide age range and vary in site, histology, and clinical behaviour. Patients with germ-cell tumours are managed by a diverse array of specialists. Thus, staging, risk stratification, and treatment approaches for germ-cell tumours have evolved disparately along several trajectories. Paediatric germ-cell tumours differ from the adolescent and adult disease in many ways, leading to complexities in applying age-appropriate, evidence-based care. Suboptimal outcomes remain for several groups of patients, including adolescents, and patients with extragonadal tumours, high tumour markers at diagnosis, or platinum-resistant disease. Survivors have significant long-term toxicities. The challenge moving forward will be to translate new insights from molecular studies and collaborative clinical data into improved patient outcomes. Future trials will be characterised by improved risk-stratification systems, biomarkers for response and toxic effects, rational reduction of therapy for low-risk patients and novel approaches for poor-risk patients, and improved international collaboration across paediatric and adult cooperative research groups. PMID:27300675

  3. The Laser Treatment of Experimental Malignant Tumours

    PubMed Central

    McGuff, Paul E.; Deterling, Ralph A.; Gottlieb, Leonard S.; Fahimi, H. Dariush; Bushnell, David; Roeber, Fred

    1964-01-01

    Some of the results of experiments performed during the past two years to assess effects of laser energy on experimental malignant tumours are reviewed. Twenty types of malignant tumours (most in the cheek pouch and 11 of human origin) were treated in over 700 Syrian hamsters. Results of laser treatment of malignant melanomas and thyroidal carcinomas are presented. A human patient with malignant melanoma treated by laser energy is described. Investigation of thermal effect revealed that the laser-treated tumour remained warm for about one minute, while the cautery-treated tumour cooled to normal temperature in five seconds. Direct action of laser on superficial tumours is possible; deeper lesions must be exposed surgically. Laser energy has a selective effect on certain malignant tumours, resulting in their progressive regression and ultimate dissolution. All hamsters with implanted malignant melanomas and carcinomas of human origin, after completion of a course of laser treatment, showed no gross or histologic evidence of tumour up to the date of last observation. ImagesFig. 1Fig. 2aFig. 2bFig. 2cFig. 2dFig. 2eFig. 2fFig. 3Fig. 4aFig. 4bFig. 4cFig. 4dFig. 4eFig. 4fFig. 4gFig. 6 PMID:14229757

  4. MRI appearances of borderline ovarian tumours.

    PubMed

    Bent, C L; Sahdev, A; Rockall, A G; Singh, N; Sohaib, S A; Reznek, R H

    2009-04-01

    This review was performed to describe the range of magnetic resonance imaging (MRI) appearances of borderline ovarian tumours. The MRI findings in 26 patients with 31 borderline ovarian tumours (mean age: 40.1 years, range: 14-85 years) were retrospectively reviewed. For each tumour, site, size, MRI characteristics, and enhancement following gadolinium administration were recorded. There were 20 serous and 11 mucinous borderline ovarian subtypes. Nine of 26 patients demonstrated bilateral disease on MRI; synchronous contralateral ovarian disease included three benign, five serous borderline, and one serous invasive tumour. A history of a metachronous mucinous borderline tumour was identified in one patient. MRI appearances were classified into four morphological categories: group 1 (6/31, 19%), unilocular cysts; group 2 (6/31, 19%), minimally septate cysts with papillary projections; group 3 (14/31, 45%), markedly septate lesions with plaque-like excrescences; and group 4 (5/31, 16%), predominantly solid with exophytic papillary projections, all of serous subtype. There was a significant difference in mean volume between serous (841.5 cm(3)) and mucinous (6358.2 cm(3)) subtypes (p=0.009). All tumours demonstrated at least one MRI feature suggestive of malignancy. The present review demonstrates the variable MRI appearances of borderline ovarian tumours along with imaging features suggestive of tumour subtype. In patients in whom the clinical features are suggestive of a borderline ovarian tumour (young age and normal or minimally elevated CA125), the ability to predict a borderline disease using morphological features observed on MRI would be extremely helpful in surgical planning, with the potential to offer fertility or ovary-preserving surgery. Future studies are required to further this aim.

  5. The Prevalence and Phenomenology of Self-Injurious and Aggressive Behaviour in Genetic Syndromes

    ERIC Educational Resources Information Center

    Arron, K.; Oliver, C.; Moss, J.; Berg, K.; Burbidge, C.

    2011-01-01

    Background: Self-injurious and aggressive behaviours are reported as components of some behavioural phenotypes but there are few studies comparing across syndrome groups. In this study we examined the prevalence of these behaviours and the associated person characteristics in seven genetic syndromes. Methods: Questionnaire data on self-injury and…

  6. The combined epithelial odontogenic tumour in Malaysians.

    PubMed

    Siar, C H; Ng, K H

    1991-04-01

    The combined epithelial odontogenic tumour represents a hybrid lesion comprising primarily areas of adenomatoid odontogenic tumour intermixed with foci of calcifying epithelial odontogenic tumour. Five such cases retrieved from the files of the Division of Stomatology, Institute for Medical Research, Kuala Lumpur, and four others from the existing literature were analysed. A mean age of 18.8 years, a female preponderance (66.7%) with a male to female ratio of 1:2 and predilection for the mandible (55.6%) were observed. All cases were treated by conservative surgery and the lack of recurrence confirmed the innocuous nature of this lesion.

  7. The prophylaxis of nonindustrial urothelial tumours

    PubMed Central

    Mount, Balfour M.

    1973-01-01

    Present knowledge concerning carcinogenesis and the natural history of urothelial tumours precludes firm conclusions relative to nonindustrial prophylaxis. However, a number of measures are consistent with current data and may be instituted for those patients with a demonstrated propensity to urothelial tumours. Their acceptability is based on the lack of associated toxicity for the patient. These measures include the elimination of significant infection, cigarettes, artificial sweeteners, analgesic abuse and coffee, the administration of vitamins C and B6, and in selected cases, the use of thiotepa. It is emphasized that the merit of these steps in altering the natural history of urothelial tumours is uncertain. PMID:4197537

  8. Inflammatory myofibroblastic tumour of the gallbladder

    PubMed Central

    Behranwala, Kasim A; Straker, Peter; Wan, Andrew; Fisher, Cyril; Thompson, Jeremy N

    2005-01-01

    Background Inflammatory myofibroblastic tumour (IMT) is a benign, nonmetastasizing proliferation of myofibroblasts with a potential for local infiltration, recurrence and persistent local growth. Case report We report a case of a 51 year-old female, who had excision of a gallbladder tumour. Histopathology showed it to be IMT of the gallbladder. Conclusion The approach to these tumours should be primarily surgical resection to obtain a definitive diagnosis and relieve symptoms. IMT has a potential for local infiltration, recurrence and persistent local growth. PMID:15862123

  9. Inflammatory myofibroblastic tumour of the gallbladder.

    PubMed

    Behranwala, Kasim A; Straker, Peter; Wan, Andrew; Fisher, Cyril; Thompson, Jeremy N

    2005-04-29

    BACKGROUND: Inflammatory myofibroblastic tumour (IMT) is a benign, nonmetastasizing proliferation of myofibroblasts with a potential for local infiltration, recurrence and persistent local growth. CASE REPORT: We report a case of a 51 year-old female, who had excision of a gallbladder tumour. Histopathology showed it to be IMT of the gallbladder. CONCLUSION: The approach to these tumours should be primarily surgical resection to obtain a definitive diagnosis and relieve symptoms. IMT has a potential for local infiltration, recurrence and persistent local growth. PMID:15862123

  10. Warthin's tumour: a retrospective case series.

    PubMed

    Taylor, T R; Cozens, N J A; Robinson, I

    2009-11-01

    Warthin's tumour (benign cystadenolymphoma) is the second most common salivary gland tumour after pleomorphic salivary adenoma, and it is commonly encountered in routine head and neck ultrasonography. Tissue diagnosis can be achieved by fine-needle aspiration. Infarction and inflammatory response following fine-needle aspiration is previously described in excision specimens. We describe 7 cases of radiologically infarcting Warthin's tumours in situ in a retrospective analysis of 76 patients, and demonstrate an approximate incidence of at least 9% of infarction following fine-needle aspiration in lesions left in situ. We recommend the possibility of infarction and associated clinical symptoms being incorporated into pre-fine-needle aspiration patient counselling.

  11. Synchronous extra-parotid Warthin's tumour.

    PubMed

    Nishikawa, H; Kirkham, N; Hogbin, B M

    1989-08-01

    Warthin's tumour (also known as adenolymphoma or papillary cystadenoma lymphomatosum) is benign and accounts for 12 per cent of all neoplasms of the parotid gland. A case of extra-parotid Warthin's tumour occurring synchronously in a peri-parotid lymph node is described. This is not a metastatic phenomenon and occurs as a result of salivary gland inclusions of local lymph nodes during the embryological development of the parotid. Extra-parotid Warthin's tumour should be regarded as a benign incidental finding and the prognosis is excellent.

  12. 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.

  13. Integrated genome and transcriptome sequencing identifies a novel form of hybrid and aggressive prostate cancer.

    PubMed

    Wu, Chunxiao; Wyatt, Alexander W; Lapuk, Anna V; McPherson, Andrew; McConeghy, Brian J; Bell, Robert H; Anderson, Shawn; Haegert, Anne; Brahmbhatt, Sonal; Shukin, Robert; Mo, Fan; Li, Estelle; Fazli, Ladan; Hurtado-Coll, Antonio; Jones, Edward C; Butterfield, Yaron S; Hach, Faraz; Hormozdiari, Fereydoun; Hajirasouliha, Iman; Boutros, Paul C; Bristow, Robert G; Jones, Steven Jm; Hirst, Martin; Marra, Marco A; Maher, Christopher A; Chinnaiyan, Arul M; Sahinalp, S Cenk; Gleave, Martin E; Volik, Stanislav V; Collins, Colin C

    2012-05-01

    Next-generation sequencing is making sequence-based molecular pathology and personalized oncology viable. We selected an individual initially diagnosed with conventional but aggressive prostate adenocarcinoma and sequenced the genome and transcriptome from primary and metastatic tissues collected prior to hormone therapy. The histology-pathology and copy number profiles were remarkably homogeneous, yet it was possible to propose the quadrant of the prostate tumour that likely seeded the metastatic diaspora. Despite a homogeneous cell type, our transcriptome analysis revealed signatures of both luminal and neuroendocrine cell types. Remarkably, the repertoire of expressed but apparently private gene fusions, including C15orf21:MYC, recapitulated this biology. We hypothesize that the amplification and over-expression of the stem cell gene MSI2 may have contributed to the stable hybrid cellular identity. This hybrid luminal-neuroendocrine tumour appears to represent a novel and highly aggressive case of prostate cancer with unique biological features and, conceivably, a propensity for rapid progression to castrate-resistance. Overall, this work highlights the importance of integrated analyses of genome, exome and transcriptome sequences for basic tumour biology, sequence-based molecular pathology and personalized oncology.

  14. Integrated genome and transcriptome sequencing identifies a novel form of hybrid and aggressive prostate cancer†

    PubMed Central

    Wu, Chunxiao; Wyatt, Alexander W; Lapuk, Anna V; McPherson, Andrew; McConeghy, Brian J; Bell, Robert H; Anderson, Shawn; Haegert, Anne; Brahmbhatt, Sonal; Shukin, Robert; Mo, Fan; Li, Estelle; Fazli, Ladan; Hurtado-Coll, Antonio; Jones, Edward C; Butterfield, Yaron S; Hach, Faraz; Hormozdiari, Fereydoun; Hajirasouliha, Iman; Boutros, Paul C; Bristow, Robert G; Jones, Steven JM; Hirst, Martin; Marra, Marco A; Maher, Christopher A; Chinnaiyan, Arul M; Sahinalp, S Cenk; Gleave, Martin E; Volik, Stanislav V; Collins, Colin C

    2013-01-01

    Next-generation sequencing is making sequence-based molecular pathology and personalized oncology viable. We selected an individual initially diagnosed with conventional but aggressive prostate adenocarcinoma and sequenced the genome and transcriptome from primary and metastatic tissues collected prior to hormone therapy. The histology-pathology and copy number profiles were remarkably homogeneous, yet it was possible to propose the quadrant of the prostate tumour that likely seeded the metastatic diaspora. Despite a homogeneous cell type, our transcriptome analysis revealed signatures of both luminal and neuroendocrine cell types. Remarkably, the repertoire of expressed but apparently private gene fusions, including C15orf21:MYC, recapitulated this biology. We hypothesize that the amplification and over-expression of the stem cell gene MSI2 may have contributed to the stable hybrid cellular identity. This hybrid luminal-neuroendocrine tumour appears to represent a novel and highly aggressive case of prostate cancer with unique biological features and, conceivably, a propensity for rapid progression to castrate-resistance. Overall, this work highlights the importance of integrated analyses of genome, exome and transcriptome sequences for basic tumour biology, sequence-based molecular pathology and personalized oncology. PMID:22294438

  15. 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…

  16. 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.

  17. 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…

  18. 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.

  19. 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…

  20. 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.…

  1. Regional tumour glutamine supply affects chromatin and cell identity.

    PubMed

    Højfeldt, Jonas W; Helin, Kristian

    2016-09-28

    Limited perfusion of solid tumours produces a nutrient-deprived tumour core microenvironment. Low glutamine levels in the tumour core are now shown to lead to reduced levels of α-ketoglutarate and decreased histone demethylase activity, thereby promoting a less differentiated and more therapy-resistant state of the tumour cells.

  2. Regional tumour glutamine supply affects chromatin and cell identity.

    PubMed

    Højfeldt, Jonas W; Helin, Kristian

    2016-09-28

    Limited perfusion of solid tumours produces a nutrient-deprived tumour core microenvironment. Low glutamine levels in the tumour core are now shown to lead to reduced levels of α-ketoglutarate and decreased histone demethylase activity, thereby promoting a less differentiated and more therapy-resistant state of the tumour cells. PMID:27684506

  3. Adenomatoid odontogenic tumour in a 20-year-old woman

    PubMed Central

    Virupakshappa, Deepti; Rajashekhara, Bhari Sharanesha; Manjunatha, Bhari Sharanesha; Das, Nagarajappa

    2014-01-01

    Adenomatoid odontogenic tumour is a relatively rare and distinct odontogenic tumour that is exclusively odontogenic epithelium in origin. It comprises 3% of all odontogenic tumours. This report describes the surgical therapy, clinical course and morphological characteristics of an adenomatoid odontogenic tumour that developed in the left maxilla of a 20-year-old patient. PMID:24810436

  4. 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.

  5. Ovarian tumours in pregnancy: a literature review.

    PubMed

    Aggarwal, Pakhee; Kehoe, Sean

    2011-04-01

    Ovarian tumours in pregnancy are a diagnostic and management challenge that is increasingly being faced by the clinician. While most masses are benign and resolve spontaneously, there are others that persist and indicate the need for surgical management. Ultrasound not only detects asymptomatic masses but also helps to guide their management based on presence or absence of features suspicious of malignancy. The role of tumour markers in pregnancy is limited due to their non-specific nature. Most masses treated in pregnancy are benign (most commonly dermoids), and most malignancies are either of low malignant potential or germ cell tumours, usually early stage disease. Surgical management is indicated for symptomatic masses or those with increasing size or complexity indicating possible malignancy. Both laparoscopy and laparotomy have similar results with regard to obstetric outcome. Conservative management is preferred in the remainder. MRI may help in better characterization of doubtful masses. National tumour registries can help to establish guidelines.

  6. A rare solitary fibrous tumour of kidney.

    PubMed

    Pathak, Tilak Bahadur; Nepal, Umesh

    2013-01-01

    A solitary fibrous tumour is an unusual spindle cell neoplasm. It frequently arises from the serosal surface of pleural cavity but has recently been described in diverse extrapleural sites. Urogenital localization is rare and only 36 cases of solitary fibrous tumours of the kidney have been described on published report. We report a case of a large solitary fibrous tumour clinically and radiologically thought to be renal cell carcinoma arising in the kidney of a 30 year old female. The radical nephrectomy was performed. The tumour was a well- circumscribed, solid mass attached to the renal pelvis without necrosis and haemorrhage. Histopathologically, a spindle cell neoplasia with alternating hypo and hypercellular areas, storiform, fascicular and hemangipericytoma like growth pattern and less cellular dense collagen deposits were observed. Immunohistochemical studies revealed reactivity for CD34, CD99 and Bcl-2 protein. PMID:24362666

  7. Tumour marker detection in oesophageal carcinoma.

    PubMed

    Mealy, K; Feely, J; Reid, I; McSweeney, J; Walsh, T; Hennessy, T P

    1996-10-01

    Levels of the tumour markers CEA, CA 19-9, CA 125 and SCC were measured in 58 patients presenting with oesophageal carcinoma and compared with levels in patients with benign oesophageal disease and levels in normal volunteers. CEA and CA 19-9 were significantly increased in the patients with oesophageal cancer, however, individual sensitivity for CEA, CA 19-9, CA 125 and SCC was only 28, 34, 10, and 32%, respectively. The combined sensitivity of all markers was 64% and specificity was 80%. There was no difference in combined tumour marker sensitivity between squamous or adenocarcinomas of the oesophagus. No consistent change in marker levels occurred with treatment, and tumour marker levels could not be significantly correlated with stage of disease or short-term survival. These results indicate that tumour marker sensitivity is too low for oesophageal cancer screening and has poor prognostic significance in those undergoing treatment.

  8. Dentigerous Cyst Associated with Adenomatoid Odontogenic Tumour

    PubMed Central

    Majumdar, Sumit; Uppala, Divya; Talasila, Sunil; Babu, Mahesh

    2015-01-01

    Adenomatoid odontogenic tumour (AOT), a tumour composed of odontogenic epithelium, is an uncommon tumour of odontogenic origin that accounts for only 2.2- 7.1% of all odontogenic tumours. Very few cases of AOT associated with Dentigerous cyst (DC) have been reported till date, most cases are in females and have a striking tendency to occur in the anterior maxilla. The present case is that of a 14-year-old female who revealed a large radiolucent lesion associated with the crown of an unerupted canine located in the left maxillary anterior region. The microscopic examination revealed the presence of AOT in the fibrous capsule of a DC. In this paper, we describe the importance of grossing, sectioning and complete examination of the slide to diagnose such hybrid lesions. PMID:26155575

  9. Mesenchymal phosphaturic tumour: early detection of recurrence

    PubMed Central

    Allevi, Fabiana; Rabbiosi, Dimitri; Mandalà, Marco; Colletti, Giacomo

    2014-01-01

    The case of a recurrent phosphaturic mesenchymal tumour of the maxillary sinus 10 years after the first surgical excision is reported. The neoplasm first presented with paraneoplastic osteomalacia causing a pathological femur fracture. A right maxillary sinus tumour was identified and treated thereafter. The patient had no local symptoms and serum electrolytes returned to normal after surgical removal of the tumour. However, 10 years later, the patient's urine Ca and P levels increased and an octreoscan detected a new tumour in the right maxillary sinus. Early diagnosis prevented the effects of the paraneoplastic activity of the neoplasm. This case emphasises the importance of specific, close follow-up, because the neoplasm rarely produces local signs indicating its position. To our knowledge, this is the first reported case of a late relapse presenting without relevant symptoms (local pain or swelling or pathological fractures). PMID:24827649

  10. Systemic Effects of Non-Endocrine Tumours

    PubMed Central

    Sullivan, James D.; Rona, George

    1964-01-01

    Tumours of non-endocrine origin may exert deleterious effects by elaborating active principles which disturb body regulation. Systemic manifestations are fairly common with neoplasms of the lung, kidney, gastro-intestinal tract and thymus. The secretion of these tumours may have a known chemical structure (serotonin), may present hormone-like action (parathormone, antidiuretic hormone, insulinoid), or have well-defined biological properties (erythropoietin, gastrin-like principle). Tumours may stimulate endocrine glands by an unknown mechanism, producing disorders such as Cushing's syndrome, hypercalcemia, gynecomastia and hypoglycemia. Thymomas may be associated with autoimmune diseases. Tumours may extensively utilize or excrete some metabolite (glucose) or electrolyte (Na or K). Awareness of the systemic effects of various neoplasms may lead to an early diagnosis and proper treatment of these manifestations. PMID:14204555

  11. 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.

  12. Suppression of tumour growth by orally administered osteopontin is accompanied by alterations in tumour blood vessels

    PubMed Central

    Rittling, S R; Wejse, P L; Yagiz, K; Warot, G A; Hui, T

    2014-01-01

    Background: The integrin-binding protein osteopontin is strongly associated with tumour development, yet is an abundant dietary component as a constituent of human and bovine milk. Therefore, we tested the effect of orally administered osteopontin (o-OPN) on the development of subcutaneous tumours in mice. Methods: Bovine milk osteopontin was administered in drinking water to tumour-bearing immune-competent mice. Tumour growth, proliferation, necrosis, apoptosis and blood vessel size and number were measured. Expression of the α9 integrin was determined. Results: o-OPN suppressed tumour growth, increased the extent of necrosis, and induced formation of abnormally large blood vessels. Anti-OPN reactivity detected in the plasma of OPN-null mice fed OPN suggested that tumour-blocking peptides were absorbed during digestion, but the o-OPN effect was likely distinct from that of an RGD peptide. Expression of the α9 integrin was detected on both tumour cells and blood vessels. Potential active peptides from the α9 binding site of OPN were identified by mass spectrometry following in vitro digestion, and injection of these peptides suppressed tumour growth. Conclusions: These results suggest that peptides derived from o-OPN are absorbed and interfere with tumour growth and normal vessel development. o-OPN-derived peptides that target the α9 integrin are likely involved. PMID:24473400

  13. Unusual mass in the parapharyngeal space: a Warthin's tumour.

    PubMed

    Shaw, C-K Leslie; Sood, Sanjai; Bradley, Patrick J; Krishnan, Suren

    2006-03-01

    Parapharyngeal space (PPS) tumours are uncommon and can be a diagnostic challenge as the presenting symptoms are often vague and non-specific. Most of the PPS tumours are salivary tumours (pleomorphic adenoma being the most frequent diagnosis), and are thought to originate from minor salivary glands or the deep lobe of the parotid gland. Warthin's tumour, another benign salivary tumour involving the PPS has been rarely reported. A case of bilateral, metachronous Warthin's tumour involving the PPS is reported here. PPS Warthin's tumour is a very rare condition that if undiagnosed may result in considerable morbidity.

  14. Pineal anlage tumour - a rare entity with divergent histology.

    PubMed

    Ahuja, Arvind; Sharma, Mehar Chand; Suri, Vaishali; Sarkar, Chitra; Sharma, B S; Garg, Ajay

    2011-06-01

    Pineal anlage tumour is a rare tumour of the pineal gland that is not listed in the 2007 World Health Organization classification of tumours of the central nervous system. Pineal anlage has been defined as a primary pineal tumour with both neuroepithelial and ectomesenchymal differentiation but without endodermal differentiation. We report a pineal anlage tumour in a 4-month-old boy, the youngest patient reported with this rare tumour, with a brief review of the literature. Clinicians and neuropathologists should be aware of this entity as it is likely to be misdiagnosed as a teratoma or a melanocytic tumour of the central nervous system.

  15. 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…

  16. Cervical intra-/extramedullary solitary fibrous tumour.

    PubMed

    Ogungbo, B; Prakash, S; Kulkarni, G; Bradey, N; Marks, S M; Scoones, D

    2005-06-01

    A 53-year-old man presented with a 9-month history of symptoms of right-sided weakness, tingling and hypersentivity to clothes on both sides of the body. MRI revealed a large intraspinal intradural tumour at the level of C3-C4 in the cervical cord. The final histology was a solitary fibrous tumour (SFT) of the cervical spinal cord. The radiological diagnosis, surgical management and histology are reviewed.

  17. Early prognosis of metastasis risk in inflammatory breast cancer by texture analysis of tumour microscopic images.

    PubMed

    Kolarevic, Daniela; Tomasevic, Zorica; Dzodic, Radan; Kanjer, Ksenija; Vukosavljevic, Dragica Nikolic; Radulovic, Marko

    2015-10-01

    Inflammatory breast cancer (IBC) is a rare and aggressive type of locally advanced breast cancer. The purpose of this study was to determine the value of microscopic tumour histomorphology texture for prognosis of local and systemic recurrence at the time of initial IBC diagnosis. This retrospective study included a group of 52 patients selected on the basis of non-metastatic IBC diagnosis, stage IIIB. Gray-Level-Co-Occurrence-Matrix (GLCM) texture analysis was performed on digital images of primary tumour tissue sections stained with haematoxylin/eosin. Obtained values were categorized by use of both data- and outcome-based methods. All five acquired GLCM texture features significantly associated with metastasis outcome. By accuracies of 69-81% and AUCs of 0.71-0.81, prognostic performance of GLCM parameters exceeded that of standard major IBC clinical prognosticators such as tumour grade and response to induction chemotherapy. Furthermore, a composite score consisting of tumour grade, contrast and correlation as independent features resulted in further enhancement of prognostic performance by accuracy of 89%, discrimination efficiency by AUC of 0.93 and an outstanding hazard ratio of 71.6 (95%CI, 41.7-148.4). Internal validation was successfully performed by bootstrap and split-sample cross-validation, suggesting that the model is generalizable. This study indicates for the first time the potential use of primary breast tumour histology texture as a highly accurate, simple and cost-effective prognostic indicator of metastasis risk in IBC. Clinical relevance of the obtained results rests on the role of prognosis in decisions on induction chemotherapy and the resulting impact on quality of life and survival. PMID:26286863

  18. Tumour-initiating capacity is independent of epithelial–mesenchymal transition status in breast cancer cell lines

    PubMed Central

    Xie, G; Ji, A; Yuan, Q; Jin, Z; Yuan, Y; Ren, C; Guo, Z; Yao, Q; Yang, K; Lin, X; Chen, L

    2014-01-01

    Background: Epithelial–mesenchymal transition (EMT) and cancer stem cells (CSCs) are considered to be crucial for cancer biology. The purpose of this study was to determine whether EMT directly led to the acquisition of tumour-initiating capacity in breast cancer cell lines. Methods: Epithelial–mesenchymal transition was induced in five breast cancer cell lines and one normal breast cell line by EMT-related cytokine stimulation. Mesenchymal–epithelial transition (MET) was induced by stably overexpressing miR-200c in three mesenchymal-like breast cancer cell lines. Molecular expression and cell function analysis were performed to evaluate the effect of EMT or MET on tumour-initiating capacity and other biological characteristics. Results: The induction of EMT did not enhance tumour-initiating capacity but, instead, conferred a CD44+/CD24−/low phenotype as well as cell proliferation, migration, and resistance to doxorubicin and radiation on breast cancer cell lines. Furthermore, MET did not lead to inhibition or loss of the tumour-initiating capacity in mesenchymal-like breast cancer cell lines, but it markedly attenuated other malignant properties, including proliferation, invasion, and resistance to therapy. Conclusions: Epithelial–mesenchymal transition does not alter tumour-initiating capacity of breast cancer cells but some other biological characteristics. Therefore, EMT and tumour-initiating capacity may not be directly linked in breast cancer cell lines. PMID:24755887

  19. Consensus on biomarkers for neuroendocrine tumour disease

    PubMed Central

    Oberg, Kjell; Modlin, Irvin M; De Herder, Wouter; Pavel, Marianne; Klimstra, David; Frilling, Andrea; Metz, David C; Heaney, Anthony; Kwekkeboom, Dik; Strosberg, Jonathan; Meyer, Timothy; Moss, Steven F; Washington, Kay; Wolin, Edward; Liu, Eric; Goldenring, James

    2016-01-01

    Management of neuroendocrine neoplasia represents a clinical challenge because of its late presentation, lack of treatment options, and limitations in present imaging modalities and biomarkers to guide management. Monoanalyte biomarkers have poor sensitivity, specificity, and predictive ability. A National Cancer Institute summit, held in 2007, on neuroendocrine tumours noted biomarker limitations to be a crucial unmet need in the management of neuroendocrine tumours. A multinational consensus meeting of multidisciplinary experts in neuroendocrine tumours assessed the use of current biomarkers and defined the perquisites for novel biomarkers via the Delphi method. Consensus (at >75%) was achieved for 88 (82%) of 107 assessment questions. The panel concluded that circulating multianalyte biomarkers provide the highest sensitivity and specificity necessary for minimum disease detection and that this type of biomarker had sufficient information to predict treatment effectiveness and prognosis. The panel also concluded that no monoanalyte biomarker of neuroendocrine tumours has yet fulfilled these criteria and there is insufficient information to support the clinical use of miRNA or circulating tumour cells as useful prognostic markers for this disease. The panel considered that trials measuring multianalytes (eg, neuroendocrine gene transcripts) should also identify how such information can optimise the management of patients with neuroendocrine tumours. PMID:26370353

  20. Brain tumour-associated status epilepticus.

    PubMed

    Goonawardena, Janindu; Marshman, Laurence A G; Drummond, Katharine J

    2015-01-01

    We have reviewed the scant literature on status epilepticus in patients with brain tumours. Patients with brain tumour-associated epilepsy (TAE) appear less likely to develop status epilepticus (TASE) than patients with epilepsy in the general population (EGP) are to develop status epilepticus (SEGP). TASE is associated with lesions in similar locations as TAE; in particular, the frontal lobes. However, in contrast to TAE, where seizures commence early in the course of the disease or at presentation, TASE is more likely to occur later in the disease course and herald tumour progression. In marked contrast to TAE, where epilepsy risk is inversely proportional to Word Health Organization tumour grade, TASE risk appears to be directly proportional to tumour grade (high grade gliomas appear singularly predisposed). Whilst anti-epileptic drug (AED) resistance is more common in TAE than EGP (with resistance directly proportional to tumour grade and frontal location), TASE appears paradoxically more responsive to simple AED regimes than either TAE or SEGP. Although some results suggest that mortality may be higher with TASE than with SEGP, it is likely that (as with SEGP) the major determinant of mortality is the underlying disease process. Because all such data have been derived from retrospective studies, because TASE and SEGP are less common than TAE and EGP, and because TASE and SEGP classification has often been inconsistent, findings can only be considered preliminary: multi-centre, prospective studies are required. Whilst preliminary, our review suggests that TASE has a distinct clinical profile compared to TAE and SEGP.

  1. Solitary fibrous tumour of the chest wall.

    PubMed

    Mohtarrudin, N; Nor Hanipah, Z; Mohd Dusa, N

    2016-04-01

    Extrapleural solitary fibrous tumours (SFTs) are rare tumours characterized by patternless spindle cells with haemangiopericytoma-like vascular spaces. Previously the tumours have been classified as haemangiopericytoma, an entity that is now considered obsolete. We report a case of extrapleural SFT arising in the soft tissue of the chest wall. The patient was a 31-year-old Malay lady presenting with a mobile swelling of the right chest wall for more than five years. During excision the tumour was noted to be well-circumscribed and yellowish in colour, giving an impression of lipoma. Microscopically, the tumour had patternless architecture, characterized by hypocellular and hypercellular areas. It was composed of uniform, spindle-shaped cells displaying oval nuclei, inconspicuous nucleoli, pale cytoplasm and indistinct cell borders. The mitotic count was 2 per 10 HPF. Branching, medium-sized thin-walled blood vessels in a haemangiopericytomatous growth pattern, some with hyalinised wall were identified. The neoplastic cells were immunoreactive to CD99 and CD34 and were non-immunoreactive to Desmin, Smooth Muscle Actin, S100 protein and EMA. We elucidate the challenges in diagnosing this tumour in this unusual location.

  2. Solitary fibrous tumour of the chest wall.

    PubMed

    Mohtarrudin, N; Nor Hanipah, Z; Mohd Dusa, N

    2016-04-01

    Extrapleural solitary fibrous tumours (SFTs) are rare tumours characterized by patternless spindle cells with haemangiopericytoma-like vascular spaces. Previously the tumours have been classified as haemangiopericytoma, an entity that is now considered obsolete. We report a case of extrapleural SFT arising in the soft tissue of the chest wall. The patient was a 31-year-old Malay lady presenting with a mobile swelling of the right chest wall for more than five years. During excision the tumour was noted to be well-circumscribed and yellowish in colour, giving an impression of lipoma. Microscopically, the tumour had patternless architecture, characterized by hypocellular and hypercellular areas. It was composed of uniform, spindle-shaped cells displaying oval nuclei, inconspicuous nucleoli, pale cytoplasm and indistinct cell borders. The mitotic count was 2 per 10 HPF. Branching, medium-sized thin-walled blood vessels in a haemangiopericytomatous growth pattern, some with hyalinised wall were identified. The neoplastic cells were immunoreactive to CD99 and CD34 and were non-immunoreactive to Desmin, Smooth Muscle Actin, S100 protein and EMA. We elucidate the challenges in diagnosing this tumour in this unusual location. PMID:27126667

  3. Smooth muscle tumours of the alimentary tract.

    PubMed Central

    Diamond, T.; Danton, M. H.; Parks, T. G.

    1990-01-01

    Neoplasms arising from smooth muscle of the gastrointestinal (GI) tract are uncommon, comprising only 1% of gastrointestinal tumours. A total of 51 cases of smooth muscle tumour of the GI tract were analysed; 44 leiomyomas and 7 leiomyosarcomas. Lesions occurred in all areas from the oesophagus to the rectum, the stomach being the commonest site. Thirty-six patients had clinical features referable to the tumour. The tumour was detected during investigation or management of an unrelated disease process in 15 patients. The clinical presentation varied depending on tumour location, but abdominal pain and GI bleeding were the commonest presenting symptoms. The lesion was demonstrated preoperatively, mainly by endoscopy and barium studies, in 27 patients. Surgical excision was the treatment of choice, where possible. There was no recurrence in the leiomyoma group but four patients died in the leiomyosarcoma group. Although rare, smooth muscle tumours should be considered in situations where clinical presentation and investigations are not suggestive of any common GI disorder. The preoperative assessment and diagnosis is difficult because of the variability in clinical features and their inaccessibility to routine GI investigation. It is recommended that, where possible, the lesion, whether symptomatic or discovered incidentally, should be excised completely to achieve a cure and prevent future complications. Images Figure 3 Figure 4 PMID:2221768

  4. Myeloid cells in tumour-immune interactions.

    PubMed

    Kareva, Irina; Berezovskaya, Faina; Castillo-Chavez, Carlos

    2010-07-01

    Despite highly developed specific immune responses, tumour cells often manage to escape recognition by the immune system, continuing to grow uncontrollably. Experimental work suggests that mature myeloid cells may be central to the activation of the specific immune response. Recognition and subsequent control of tumour growth by the cells of the specific immune response depend on the balance between immature (ImC) and mature (MmC) myeloid cells in the body. However, tumour cells produce cytokines that inhibit ImC maturation, altering the balance between ImC and MmC. Hence, the focus of this manuscript is on the study of the potential role of this inhibiting mechanism on tumour growth dynamics. A conceptual predator-prey type model that incorporates the dynamics and interactions of tumour cells, CD8(+) T cells, ImC and MmC is proposed in order to address the role of this mechanism. The prey (tumour) has a defence mechanism (blocking the maturation of ImC) that prevents the predator (immune system) from recognizing it. The model, a four-dimensional nonlinear system of ordinary differential equations, is reduced to a two-dimensional system using time-scale arguments that are tied to the maturation rate of ImC. Analysis shows that the model is capable of supporting biologically reasonable patterns of behaviour depending on the initial conditions. A range of parameters, where healing without external influences can occur, is identified both qualitatively and quantitatively.

  5. Epithelial-myoepithelial tumour of the lung: a case report referring to its molecular histogenesis.

    PubMed

    Muñoz, Guillermo; Felipo, Francesc; Marquina, Isabel; Del Agua, Celia

    2011-07-28

    Tracheobronchial submucous glands can be considered the pulmonary equivalent of minor salivary glands and therefore they can develop most of the tumours originated in these. Nevertheless, in spite of the wide distribution of this kind of glands along the tracheobronchial tree, pulmonary salivary gland-like neoplasms are not very frequent. Among them, the most frequent are mucoepidermoid and adenoid cystic carcinomas. On the contrary, pulmonary neoplasms showing a mixture of epithelial and myoepithelial elements are extraordinary infrequent, with only 11 cases collected from literature.We present the case of a 76 year-old woman with no interesting pathological history, to whom a pulmonary nodule is detected during a study of unknown origin neutropenia. An upper right lobectomy is performed.After macro and microscopic study, the diagnosis of pulmonary epithelial-myoepithelial tumour is made. It is a low malignant potential tumour with capacity to locally recur and less frequently to metastasize. Our case has the peculiarity of not being connected neither to visceral pleura nor to bronchial tree; we have not found this characteristic in any literature reviewed case.These tumours have been named in a lot of different ways, including adenomyoepithelioma, epithelial-myoepithelial tumour, epithelial-myoepithelial carcinoma or epithelial-myoepithelial tumour of uncertain malignant potential.The p27/kip-1 protein plays a fundamental role in the development of these neoplasms. As we have verified in our case, its aberrant cytoplasmic location, besides its proved oncogenic function, would favour the proliferation of stem cells, which would explain both dual phenotype with presence of myoepithelial cells without connection with the bronchial tree, and TTF-1 immunostaining in epithelial cells.

  6. Epithelial-myoepithelial tumour of the lung: a case report referring to its molecular histogenesis

    PubMed Central

    2011-01-01

    Tracheobronchial submucous glands can be considered the pulmonary equivalent of minor salivary glands and therefore they can develop most of the tumours originated in these. Nevertheless, in spite of the wide distribution of this kind of glands along the tracheobronchial tree, pulmonary salivary gland-like neoplasms are not very frequent. Among them, the most frequent are mucoepidermoid and adenoid cystic carcinomas. On the contrary, pulmonary neoplasms showing a mixture of epithelial and myoepithelial elements are extraordinary infrequent, with only 11 cases collected from literature. We present the case of a 76 year-old woman with no interesting pathological history, to whom a pulmonary nodule is detected during a study of unknown origin neutropenia. An upper right lobectomy is performed. After macro and microscopic study, the diagnosis of pulmonary epithelial-myoepithelial tumour is made. It is a low malignant potential tumour with capacity to locally recur and less frequently to metastasize. Our case has the peculiarity of not being connected neither to visceral pleura nor to bronchial tree; we have not found this characteristic in any literature reviewed case. These tumours have been named in a lot of different ways, including adenomyoepithelioma, epithelial-myoepithelial tumour, epithelial-myoepithelial carcinoma or epithelial-myoepithelial tumour of uncertain malignant potential. The p27/kip-1 protein plays a fundamental role in the development of these neoplasms. As we have verified in our case, its aberrant cytoplasmic location, besides its proved oncogenic function, would favour the proliferation of stem cells, which would explain both dual phenotype with presence of myoepithelial cells without connection with the bronchial tree, and TTF-1 immunostaining in epithelial cells. PMID:21798017

  7. Combined radiotherapy and chemotherapy for high-grade brain tumours

    NASA Astrophysics Data System (ADS)

    Barazzuol, Lara

    Glioblastoma (GBM) is the most common primary brain tumour in adults and among the most aggressive of all tumours. For several decades, the standard care of GBM was surgical resection followed by radiotherapy alone. In 2005, a landmark phase III clinical trial coordinated by the European Organization for Research and Treatment of Cancer (EORTC) and the National Cancer Institute of Canada (NCIC) demonstrated the benefit of radiotherapy with concomitant and adjuvant temozolomide (TMZ) chemotherapy. With TMZ, the median life expectancy in optimally managed patients is still only 12-14 months, with only 25% surviving 24 months. There is an urgent need for new therapies in particular in those patients whose tumour has an unmethylated methylguanine methyltransferase gene (MGMT) promoter, which is a predictive factor of benefit from TMZ. In this dissertation, the nature of the interaction between TMZ and radiation is investigated using both a mathematical model, based on in vivo population statistics of survival, and in vitro experimentation on a panel of human GBM cell lines. The results show that TMZ has an additive effect in vitro and that the population-based model may be insufficient in predicting TMZ response. The combination of TMZ with particle therapy is also investigated. Very little preclinical data exists on the effects of charged particles on GBM cell lines as well as on the concomitant application of chemotherapy. In this study, human GBM cells are exposed to 3 MeV protons and 6 MeV alpha particles in concomitance with TMZ. The results suggest that the radiation quality does not affect the nature of the interaction between TMZ and radiation, showing reproducible additive cytotoxicity. Since TMZ and radiation cause DNA damage in cancer cells, there has been increased attention to the use of poly(ADP-ribose) polymerase (PARP) inhibitors. PARP is a family of enzymes that play a key role in the repair of DNA breaks. In this study, a novel PARP inhibitor, ABT-888

  8. Procoagulant activity may be a marker of the malignant phenotype in experimental prostate cancer.

    PubMed Central

    Adamson, A. S.; Luckert, P.; Pollard, M.; Snell, M. E.; Amirkhosravi, M.; Francis, J. L.

    1994-01-01

    Using a one-stage kinetic chromogenic assay, we studied the procoagulant activity (PCA) of prostatic tissue in an experimental model of prostate cancer in the rat. PCA was present in homogenates of rat prostate glands containing either benign or malignant tumours. The procoagulant activated factor X directly and was provisionally characterised as a tissue factor-factor VIIa complex. There was no significant differences in PCA between control rats and rats exposed to carcinogens that did not develop tumour. Levels in rats that developed tumours were significantly higher (P < 0.01) than all other groups and there was a positive correlation between tumour weight and PCA (r = 0.85, P < 0.001). Furthermore, prostatic PCA levels were higher in the metastasis (P < 0.02). We conclude that PCA reflects the malignant phenotype in this animals, the PCA of the primary tumour was compared with that of the corresponding secondary deposit and levels were higher in the metastasis (P < 0.02). We conclude that PCA reflects the malignant phenotype in this model of experimental prostate cancer and suggest that this parameter is worth evaluating as a potential tumour marker in the human disease. PMID:8297726

  9. 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…

  10. 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.

  11. 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…

  12. Tumour nuclear oestrogen receptor beta 1 correlates inversely with parathyroid tumour weight

    PubMed Central

    Haglund, Felix; Rosin, Gustaf; Nilsson, Inga-Lena; Juhlin, C Christofer; Pernow, Ylva; Norenstedt, Sophie; Dinets, Andrii; Larsson, Catharina; Hartman, Johan; Höög, Anders

    2015-01-01

    Primary hyperparathyroidism (PHPT) is a common endocrinopathy, frequently caused by a parathyroid adenoma, rarely by a parathyroid carcinoma that lacks effective oncological treatment. As the majority of cases are present in postmenopausal women, oestrogen signalling has been implicated in the tumourigenesis. Oestrogen receptor beta 1 (ERB1) and ERB2 have been recently identified in parathyroid adenomas, the former inducing genes coupled to tumour apoptosis. We applied immunohistochemistry and slide digitalisation to quantify nuclear ERB1 and ERB2 in 172 parathyroid adenomas, atypical adenomas and carcinomas, and ten normal parathyroid glands. All the normal parathyroid glands expressed ERB1 and ERB2. The majority of tumours expressed ERB1 (70.6%) at varying intensities, and ERB2 (96.5%) at strong intensities. Parathyroid carcinomas expressed ERB1 in three out of six cases and ERB2 in five out of six cases. The intensity of tumour nuclear ERB1 staining significantly correlated inversely with tumour weight (P=0.011), and patients whose tumours were classified as ERB1-negative had significantly greater tumour weight as well as higher serum calcium (P=0.002) and parathyroid hormone levels (P=0.003). Additionally, tumour nuclear ERB1 was not expressed differentially with respect to sex or age of the patient. Levels of tumour nuclear ERB2 did not correlate with clinical characteristics. In conclusion, decreased ERB1 immunoreactivity is associated with increased tumour weight in parathyroid adenomas. Given the previously reported correlation with tumour-suppressive signalling, selective oestrogen receptor modulation (SERMs) may play a role in the treatment of parathyroid carcinomas. Future studies of SERMs and oestrogen treatment in PHPT should consider tumour weight as a potential factor in pharmacological responsiveness. PMID:25648860

  13. Tumour nuclear oestrogen receptor beta 1 correlates inversely with parathyroid tumour weight.

    PubMed

    Haglund, Felix; Rosin, Gustaf; Nilsson, Inga-Lena; Juhlin, C Christofer; Pernow, Ylva; Norenstedt, Sophie; Dinets, Andrii; Larsson, Catharina; Hartman, Johan; Höög, Anders

    2015-03-01

    Primary hyperparathyroidism (PHPT) is a common endocrinopathy, frequently caused by a parathyroid adenoma, rarely by a parathyroid carcinoma that lacks effective oncological treatment. As the majority of cases are present in postmenopausal women, oestrogen signalling has been implicated in the tumourigenesis. Oestrogen receptor beta 1 (ERB1) and ERB2 have been recently identified in parathyroid adenomas, the former inducing genes coupled to tumour apoptosis. We applied immunohistochemistry and slide digitalisation to quantify nuclear ERB1 and ERB2 in 172 parathyroid adenomas, atypical adenomas and carcinomas, and ten normal parathyroid glands. All the normal parathyroid glands expressed ERB1 and ERB2. The majority of tumours expressed ERB1 (70.6%) at varying intensities, and ERB2 (96.5%) at strong intensities. Parathyroid carcinomas expressed ERB1 in three out of six cases and ERB2 in five out of six cases. The intensity of tumour nuclear ERB1 staining significantly correlated inversely with tumour weight (P=0.011), and patients whose tumours were classified as ERB1-negative had significantly greater tumour weight as well as higher serum calcium (P=0.002) and parathyroid hormone levels (P=0.003). Additionally, tumour nuclear ERB1 was not expressed differentially with respect to sex or age of the patient. Levels of tumour nuclear ERB2 did not correlate with clinical characteristics. In conclusion, decreased ERB1 immunoreactivity is associated with increased tumour weight in parathyroid adenomas. Given the previously reported correlation with tumour-suppressive signalling, selective oestrogen receptor modulation (SERMs) may play a role in the treatment of parathyroid carcinomas. Future studies of SERMs and oestrogen treatment in PHPT should consider tumour weight as a potential factor in pharmacological responsiveness. PMID:25648860

  14. 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…

  15. 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…

  16. 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.

  17. Juvenile aggressive cemento-ossifying fibroma of the sphenoid sinus with proptosis: a surgical dilemma.

    PubMed

    Singh, Rohit; Ramaswamy, Balakrishnan; Hazarika, Manali

    2013-01-01

    The term fibro-osseous lesion has currently grown in popularity as an overall designation for a number of rare, histologically benign head and neck lesions that are made up of bone, fibrous tissue and cementum. Cemento-ossifying fibroma is a variant of cementifying fibroma and is a fibro-osseous disease. They are usually small innocuous lesions which follow a slow benign course and are commonly seen in the skull bone rather than the sphenoid. It is rare for these tumours to attain large size, behave aggressively, destroy bone and require a radical surgery. One such rapidly growing juvenile cemento-ossifying lesion of sphenoid in our 10-year-old young patient causing proptosis and impaired vision is reported here because of its uncommon nature and its surgical dilemma. Selection of surgical approach to resect this tumour becomes difficult because it is deeply seated and needs a multidisciplinary approach. PMID:24285811

  18. Juvenile aggressive cemento-ossifying fibroma of the sphenoid sinus with proptosis: a surgical dilemma.

    PubMed

    Singh, Rohit; Ramaswamy, Balakrishnan; Hazarika, Manali

    2013-11-27

    The term fibro-osseous lesion has currently grown in popularity as an overall designation for a number of rare, histologically benign head and neck lesions that are made up of bone, fibrous tissue and cementum. Cemento-ossifying fibroma is a variant of cementifying fibroma and is a fibro-osseous disease. They are usually small innocuous lesions which follow a slow benign course and are commonly seen in the skull bone rather than the sphenoid. It is rare for these tumours to attain large size, behave aggressively, destroy bone and require a radical surgery. One such rapidly growing juvenile cemento-ossifying lesion of sphenoid in our 10-year-old young patient causing proptosis and impaired vision is reported here because of its uncommon nature and its surgical dilemma. Selection of surgical approach to resect this tumour becomes difficult because it is deeply seated and needs a multidisciplinary approach.

  19. 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

  20. 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

  1. 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.

  2. Tumour-induced neoneurogenesis and perineural tumour growth: a mathematical approach

    PubMed Central

    Lolas, Georgios; Bianchi, Arianna; Syrigos, Konstantinos N.

    2016-01-01

    It is well-known that tumours induce the formation of a lymphatic and a blood vasculature around themselves. A similar but far less studied process occurs in relation to the nervous system and is referred to as neoneurogenesis. The relationship between tumour progression and the nervous system is still poorly understood and is likely to involve a multitude of factors. It is therefore relevant to study tumour-nerve interactions through mathematical modelling: this may reveal the most significant factors of the plethora of interacting elements regulating neoneurogenesis. The present work is a first attempt to model the neurobiological aspect of cancer development through a system of differential equations. The model confirms the experimental observations that a tumour is able to promote nerve formation/elongation around itself, and that high levels of nerve growth factor and axon guidance molecules are recorded in the presence of a tumour. Our results also reflect the observation that high stress levels (represented by higher norepinephrine release by sympathetic nerves) contribute to tumour development and spread, indicating a mutually beneficial relationship between tumour cells and neurons. The model predictions suggest novel therapeutic strategies, aimed at blocking the stress effects on tumour growth and dissemination. PMID:26861829

  3. Tumour-induced neoneurogenesis and perineural tumour growth: a mathematical approach.

    PubMed

    Lolas, Georgios; Bianchi, Arianna; Syrigos, Konstantinos N

    2016-01-01

    It is well-known that tumours induce the formation of a lymphatic and a blood vasculature around themselves. A similar but far less studied process occurs in relation to the nervous system and is referred to as neoneurogenesis. The relationship between tumour progression and the nervous system is still poorly understood and is likely to involve a multitude of factors. It is therefore relevant to study tumour-nerve interactions through mathematical modelling: this may reveal the most significant factors of the plethora of interacting elements regulating neoneurogenesis. The present work is a first attempt to model the neurobiological aspect of cancer development through a system of differential equations. The model confirms the experimental observations that a tumour is able to promote nerve formation/elongation around itself, and that high levels of nerve growth factor and axon guidance molecules are recorded in the presence of a tumour. Our results also reflect the observation that high stress levels (represented by higher norepinephrine release by sympathetic nerves) contribute to tumour development and spread, indicating a mutually beneficial relationship between tumour cells and neurons. The model predictions suggest novel therapeutic strategies, aimed at blocking the stress effects on tumour growth and dissemination. PMID:26861829

  4. Tumour-induced neoneurogenesis and perineural tumour growth: a mathematical approach

    NASA Astrophysics Data System (ADS)

    Lolas, Georgios; Bianchi, Arianna; Syrigos, Konstantinos N.

    2016-02-01

    It is well-known that tumours induce the formation of a lymphatic and a blood vasculature around themselves. A similar but far less studied process occurs in relation to the nervous system and is referred to as neoneurogenesis. The relationship between tumour progression and the nervous system is still poorly understood and is likely to involve a multitude of factors. It is therefore relevant to study tumour-nerve interactions through mathematical modelling: this may reveal the most significant factors of the plethora of interacting elements regulating neoneurogenesis. The present work is a first attempt to model the neurobiological aspect of cancer development through a system of differential equations. The model confirms the experimental observations that a tumour is able to promote nerve formation/elongation around itself, and that high levels of nerve growth factor and axon guidance molecules are recorded in the presence of a tumour. Our results also reflect the observation that high stress levels (represented by higher norepinephrine release by sympathetic nerves) contribute to tumour development and spread, indicating a mutually beneficial relationship between tumour cells and neurons. The model predictions suggest novel therapeutic strategies, aimed at blocking the stress effects on tumour growth and dissemination.

  5. 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.

  6. Small cell neuroendocrine tumour of the endometrium and the importance of pathologic diagnosis.

    PubMed

    Estruch, Adriana; Minig, Lucas; Illueca, Carmen; Romero, Ignacio; Guinot, Jose Luis; Poveda, Andrés

    2016-01-01

    Small cell carcinoma of the endometrium is a very rare entity. They are very aggressive tumours, with a poor prognosis. They represent a clinical challenge because of a lack of a standardised treatment. We see here a case of a 67-year-old woman with a history of a lobular breast carcinoma, diagnosed in 2002. After presenting with postmenopausal vaginal bleeding in October 2014, she underwent a hysteroscopy-guided biopsy which revealed a metastasis of breast carcinoma. A hysterectomy and bilateral oophorectomy was performed because of uncontrolled uterine bleeding. The pathologic diagnosis was small cell carcinoma (SCC) of the endometrium. A surgical complete cytoreduction was achieved after the case being presented in a multidisciplinary tumour board. Pathologic results revealed metastasis from peritoneal implants of SCC on the endometrium, and metastasis in pelvic and para-aortic lymph nodes from serous carcinoma of the endometrium. A total of four cycles of adjuvant chemotherapy based on cisplatin (80mg/m² day one) and etoposide (100mg/m² day one, two, three) every 21 days was given. The patient experienced persistent disease and died 17 months after the diagnosis. SCC of the endometrium is a very rare and aggressive disease that requires an individualised multidisciplinary management. PMID:27610194

  7. Small cell neuroendocrine tumour of the endometrium and the importance of pathologic diagnosis

    PubMed Central

    Estruch, Adriana; Minig, Lucas; Illueca, Carmen; Romero, Ignacio; Guinot, Jose Luis; Poveda, Andrés

    2016-01-01

    Small cell carcinoma of the endometrium is a very rare entity. They are very aggressive tumours, with a poor prognosis. They represent a clinical challenge because of a lack of a standardised treatment. We see here a case of a 67-year-old woman with a history of a lobular breast carcinoma, diagnosed in 2002. After presenting with postmenopausal vaginal bleeding in October 2014, she underwent a hysteroscopy-guided biopsy which revealed a metastasis of breast carcinoma. A hysterectomy and bilateral oophorectomy was performed because of uncontrolled uterine bleeding. The pathologic diagnosis was small cell carcinoma (SCC) of the endometrium. A surgical complete cytoreduction was achieved after the case being presented in a multidisciplinary tumour board. Pathologic results revealed metastasis from peritoneal implants of SCC on the endometrium, and metastasis in pelvic and para-aortic lymph nodes from serous carcinoma of the endometrium. A total of four cycles of adjuvant chemotherapy based on cisplatin (80mg/m² day one) and etoposide (100mg/m² day one, two, three) every 21 days was given. The patient experienced persistent disease and died 17 months after the diagnosis. SCC of the endometrium is a very rare and aggressive disease that requires an individualised multidisciplinary management. PMID:27610194

  8. Small cell neuroendocrine tumour of the endometrium and the importance of pathologic diagnosis

    PubMed Central

    Estruch, Adriana; Minig, Lucas; Illueca, Carmen; Romero, Ignacio; Guinot, Jose Luis; Poveda, Andrés

    2016-01-01

    Small cell carcinoma of the endometrium is a very rare entity. They are very aggressive tumours, with a poor prognosis. They represent a clinical challenge because of a lack of a standardised treatment. We see here a case of a 67-year-old woman with a history of a lobular breast carcinoma, diagnosed in 2002. After presenting with postmenopausal vaginal bleeding in October 2014, she underwent a hysteroscopy-guided biopsy which revealed a metastasis of breast carcinoma. A hysterectomy and bilateral oophorectomy was performed because of uncontrolled uterine bleeding. The pathologic diagnosis was small cell carcinoma (SCC) of the endometrium. A surgical complete cytoreduction was achieved after the case being presented in a multidisciplinary tumour board. Pathologic results revealed metastasis from peritoneal implants of SCC on the endometrium, and metastasis in pelvic and para-aortic lymph nodes from serous carcinoma of the endometrium. A total of four cycles of adjuvant chemotherapy based on cisplatin (80mg/m² day one) and etoposide (100mg/m² day one, two, three) every 21 days was given. The patient experienced persistent disease and died 17 months after the diagnosis. SCC of the endometrium is a very rare and aggressive disease that requires an individualised multidisciplinary management.

  9. Evolution of a contagious cancer: epigenetic variation in Devil Facial Tumour Disease.

    PubMed

    Ujvari, Beata; Pearse, Anne-Maree; Peck, Sarah; Harmsen, Collette; Taylor, Robyn; Pyecroft, Stephen; Madsen, Thomas; Papenfuss, Anthony T; Belov, Katherine

    2013-01-01

    The emergence of Devil Facial Tumour Disease (DFTD), a highly contagious cancer, is driving Tasmanian devils (Sarcophilus harrisii) to extinction. The cancer is a genetically and chromosomally stable clonal cell line which is transmitted by biting during social interactions. In the present study, we explore the Devil Facial Tumour (DFT) epigenome and the genes involved in DNA methylation homeostasis. We show that tumour cells have similar levels of methylation to peripheral nerves, the tissue from which DFTD originated. We did not observe any strain or region-specific epimutations. However, we revealed a significant increase in hypomethylation in DFT samples over time (p < 0.0001). We propose that loss of methylation is not because of a maintenance deficiency, as an upregulation of DNA methyltransferase 1 gene was observed in tumours compared with nerves (p < 0.005). Instead, we believe that loss of methylation is owing to active demethylation, supported by the temporal increase in MBD2 and MBD4 (p < 0.001). The implications of these changes on disease phenotypes need to be explored. Our work shows that DFTD should not be treated as a static entity, but rather as an evolving parasite with epigenetic plasticity. Understanding the role of epimutations in the evolution of this parasitic cancer will provide unique insights into the role of epigenetic plasticity in cancer evolution and progression in traditional cancers that arise and die with their hosts.

  10. The significance of circulating tumour cells in breast cancer: a review.

    PubMed

    Castle, J; Shaker, H; Morris, K; Tugwood, J D; Kirwan, C C

    2014-10-01

    Haematogenous spread of circulating tumour cells (CTCs) is the principle mechanism for development of metastases. Research into the enumeration and characterisation of CTCs, particularly in the last decade, has allowed the introduction of semi-automated CTC assessment in the clinical setting. In breast cancer, CTC enumeration is being used as a prognostic biomarker, a predictive biomarker of treatment response and is being assessed to guide treatment in both the early and metastatic setting. CTC characterisation has the potential to direct targeted therapies, such as HER2 therapies in HER2 negative primary breast tumour patients. However, CTC assessment has considerable challenges. Capture and identification of these very rare cells is currently largely dependent on a presumed homogeneity of phenotype. In addition, high throughput assays are lacking. The clinical significance of CTCs is incompletely understood. A large proportion of CTC positive patients have no evidence of metastases, raising the issue of either inconsequential tumour dormancy or non-viable CTCs. CTCs may have additional clinical sequelae such as promoting venous thrombosis. However CTCs provide a real-time liquid biopsy of the tumour and represent an exciting, minimally invasive method of assessing disease status and also a novel therapeutic target for malignancy.

  11. CD34 immunoexpression in stromal tumours of the gastrointestinal tract and in mesenteric fibromatoses.

    PubMed

    Monihan, J M; Carr, N J; Sobin, L H

    1994-11-01

    The aim of this study was to explore whether CD34 immunoreactivity can distinguish between different types of gastrointestinal stromal tumour, i.e. smooth muscle and neurogenic. We studied 87 stromal tumours from different sites in the gastrointestinal tract, as well as the omentum and mesentery, using a monoclonal antibody to CD34 (QBEND10). We also determined the immunoexpression of smooth muscle and muscle specific actins, S-100 protein, cytokeratin, desmin and vimentin. In addition, 15 cases of mesenteric fibromatosis were tested for CD34. Immunoexpression of CD34 was observed in 40 of the 87 stromal tumours and correlated with evidence of differentiation towards a smooth muscle phenotype. Large intestinal stromal tumours were less likely than gastric lesions to be CD34 positive. None of 15 cases of mesenteric fibromatosis was positive for CD34. We conclude that CD34 immunoexpression is seen in a proportion of stromal tumors of the gastrointestinal tract, mesentery and omentum, particularly those of smooth muscle type, and it may be useful as part of an immunohistochemical panel in the differential diagnosis of these neoplasms.

  12. Blocking CLEC14A-MMRN2 binding inhibits sprouting angiogenesis and tumour growth

    PubMed Central

    PJ, Noy; P, Lodhia; K, Khan; X, Zhuang; DG, Ward; AR, Verissimo; A, Bacon; R, Bicknell

    2015-01-01

    We previously identified CLEC14A as a tumour endothelial marker. Here we show CLEC14A is a regulator of sprouting angiogenesis in vitro and in vivo. Using a HUVEC spheroid sprouting assay we found CLEC14A to be a regulator of sprout initiation. Analysis of endothelial sprouting in aortic ring and in vivo subcutaneous sponge assays from clec14a+/+ and clec14a−/− mice revealed defects in sprouting angiogenesis in CLEC14A deficient animals. Tumour growth was retarded and vascularity reduced in clec14a−/− mice. Pulldown and co-immunoprecipitation experiments confirmed MMRN2 binds to the extracellular region of CLEC14A. The CLEC14A-MMRN2 interaction was interrogated using mouse monoclonal antibodies. Monoclonal antibodies were screened for their ability to block this interaction. Clone C4 but not C2 blocked CLEC14A-MMRN2 binding. C4 antibody perturbed tube formation and endothelial sprouting in vitro and in vivo, with a similar phenotype to loss of CLEC14A. Significantly, tumour growth was impaired in C4 treated animals and vascular density was also reduced in the C4 treated group. We conclude that CLEC14A-MMRN2 binding has a role in inducing sprouting angiogenesis during tumour growth, that has the potential to be manipulated in future anti-angiogenic therapy design. PMID:25745997

  13. Blocking CLEC14A-MMRN2 binding inhibits sprouting angiogenesis and tumour growth.

    PubMed

    Noy, P J; Lodhia, P; Khan, K; Zhuang, X; Ward, D G; Verissimo, A R; Bacon, A; Bicknell, R

    2015-11-19

    We previously identified CLEC14A as a tumour endothelial marker. Here we show that CLEC14A is a regulator of sprouting angiogenesis in vitro and in vivo. Using a human umbilical vein endothelial cell spheroid-sprouting assay, we found CLEC14A to be a regulator of sprout initiation. Analysis of endothelial sprouting in aortic ring and in vivo subcutaneous sponge assays from clec14a(+/+) and clec14a(-/-) mice revealed defects in sprouting angiogenesis in CLEC14A-deficient animals. Tumour growth was retarded and vascularity reduced in clec14a(-/-) mice. Pull-down and co-immunoprecipitation experiments confirmed that MMRN2 binds to the extracellular region of CLEC14A. The CLEC14A-MMRN2 interaction was interrogated using mouse monoclonal antibodies. Monoclonal antibodies were screened for their ability to block this interaction. Clone C4, but not C2, blocked CLEC14A-MMRN2 binding. C4 antibody perturbed tube formation and endothelial sprouting in vitro and in vivo, with a similar phenotype to loss of CLEC14A. Significantly, tumour growth was impaired in C4-treated animals and vascular density was also reduced in the C4-treated group. We conclude that CLEC14A-MMRN2 binding has a role in inducing sprouting angiogenesis during tumour growth, which has the potential to be manipulated in future antiangiogenic therapy design. PMID:25745997

  14. Immunological Characterization of Whole Tumour Lysate-Loaded Dendritic Cells for Cancer Immunotherapy

    PubMed Central

    Ottobrini, Luisa; Biasin, Mara; Borelli, Manuela; Lucignani, Giovanni; Trabattoni, Daria; Clerici, Mario

    2016-01-01

    Introduction Dendritic cells play a key role as initiators of T-cell responses, and even if tumour antigen-loaded dendritic cells can induce anti-tumour responses, their efficacy has been questioned, suggesting a need to enhance immunization strategies. Matherials & Methods We focused on the characterization of bone marrow-derived dendritic cells pulsed with whole tumour lysate (TAA-DC), as a source of known and unknown antigens, in a mouse model of breast cancer (MMTV-Ras). Dendritic cells were evaluated for antigen uptake and for the expression of MHC class I/II and costimulatory molecules and markers associated with maturation. Results Results showed that antigen-loaded dendritic cells are characterized by a phenotypically semi-mature/mature profile and by the upregulation of genes involved in antigen presentation and T-cell priming. Activated dendritic cells stimulated T-cell proliferation and induced the production of high concentrations of IL-12p70 and IFN-γ but only low levels of IL-10, indicating their ability to elicit a TH1-immune response. Furthermore, administration of Antigen loaded-Dendritic Cells in MMTV-Ras mice evoked a strong anti-tumour response in vivo as demonstrated by a general activation of immunocompetent cells and the release of TH1 cytokines. Conclusion Data herein could be useful in the design of antitumoral DC-based therapies, showing a specific activation of immune system against breast cancer. PMID:26795765

  15. Novel germline mutations in the PTEN tumour suppressor gene found in women with multiple cancers

    PubMed Central

    De Vivo, I.; Gertig, D.; Nagase, S.; Hankinson, S.; O'Brien, R.; Speizer, F.; Parsons, R.; Hunter, D.

    2000-01-01

    Germline mutations in PTEN can predispose people to Cowden syndrome (CS) and Bannayan-Ruvalcaba-Riley (BRR) syndrome, rare, autosomal dominantly inherited neoplastic disorders. To determine whether germline mutations in PTEN contribute to genetic predisposition to multiple primary tumours within the general population, we conducted a nested case-control study, among 32 826 members of the prospective Nurses' Health Study cohort; cases were women with more than one primary tumour at different anatomical sites. We screened all nine exons of PTEN and flanking intronic splice sites for all 103 eligible cases using SSCP and sequencing. We observed two novel germline heterozygous missense mutations in exon 5 in five of the cases; three were V119L and two were V158L. Neither mutation was observed in 115 controls free of diagnosed cancer (p=0.02). Both mutants showed partial tumour suppressor activity when compared to wild type PTEN when transfected into a PTEN null breast cancer cell line. The phenotype was cell line specific suggesting that genetic background affects growth suppression activity of the mutants. These data provide evidence that germline mutations in PTEN may be a more frequent predisposing factor for cancers in women than previously suggested.


Keywords: population based; tumour suppressor; multiple cancers; germline mutations PMID:10807691

  16. Individual responsiveness to shock and colony-level aggression in honey bees: evidence for a genetic component

    PubMed Central

    Avalos, Arian; Rodríguez-Cruz, Yoselyn; Giray, Tugrul

    2015-01-01

    The phenotype of the social group is related to phenotypes of individuals that form that society. We examined how honey bee colony aggressiveness relates to individual response of male drones and foraging workers. Although the natural focus in colony aggression has been on the worker caste, the sterile females engaged in colony maintenance and defense, males carry the same genes. We measured aggressiveness scores of colonies and examined components of individual aggressive behavior in workers and haploid sons of workers from the same colony. We describe for the first time, that males, although they have no stinger, do bend their abdomen (abdominal flexion) in a posture similar to stinging behavior of workers in response to electric shock. Individual worker sting response and movement rates in response to shock were significantly correlated with colony scores. In the case of drones, sons of workers from the same colonies, abdominal flexion significantly correlated but their movement rates did not correlate with colony aggressiveness. Furthermore, the number of workers responding at increasing levels of voltage exhibits a threshold-like response, whereas the drones respond in increasing proportion to shock. We conclude that there are common and caste-specific components to aggressive behavior in honey bees. We discuss implications of these results on social and behavioral regulation and genetics of aggressive response. PMID:25729126

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. Vascular tumours in infants. Part I: benign vascular tumours other than infantile haemangioma.

    PubMed

    Hoeger, P H; Colmenero, I

    2014-09-01

    Vascular anomalies can be subdivided into vascular tumours and vascular malformations (VMs). While most VMs are present at birth and do not exhibit significant postnatal growth, vascular tumours are characterized by their dynamics of growth and (sometimes) spontaneous regression. This review focuses on benign vascular tumours other than infantile haemangiomas (IHs), namely pyogenic granuloma, eruptive pseudoangiomatosis, glomangioma, rapidly involuting and noninvoluting congenital haemangioma, verrucous haemangioma and spindle cell haemangioma. While some of them bear clinical resemblance to IH, they can be separated by age of appearance, growth characteristics and/or negative staining for glucose transporter 1. Separation of these tumours from IH is necessary because their outcome and therapeutic options are different. Semimalignant and malignant vascular tumours will be addressed in a separate review.

  2. Synchronous gastric inflammatory myofibroblastic tumour with gastrointestinal stromal tumour of the stomach and hepatic syringious haemangioma

    PubMed Central

    Papadopoulou, D; Chatziralli, IP; Papadopoulos, V; Filitantzi, C; Demertzidis, C

    2012-01-01

    Inflammatory myofibroblastic tumour of the stomach is a very rare lesion. A case of a gastric inflammatory myofibroblastic tumour associated with gastrointestinal stromal tumour of the stomach and hepatic syringious haemangioma is described. We report an 80-year-old male who had an exophytic mass in the area of the pylorus and the duodenum, where hepatic cysts were found in the magnetic resonance (MRI) scan on examination of hypochromic microcytic anaemia, and prolapsus and torsion of the bulb of the stomach found during gastroscopy. During surgical excision of the exophytic mass, a gastrointestinal stromal tumour from the gastric fundus and a syringious haemangioma from the superior hepatic surface were resected. All tumours were treated successfully by surgical excision. The patient had an uneventful recovery. Neither recurrence nor metastasis was found after a 12-month follow-up. To our knowledge, this is the first time that such an association is reported in the literature. PMID:24960722

  3. Desmoplastic nested spindle cell tumours and nested stromal epithelial tumours of the liver.

    PubMed

    Misra, Sunayana; Bihari, Chhagan

    2016-04-01

    Desmoplastic nested spindle cell tumour of liver (DNSTL), nested stromal-epithelial tumour (NSET) and calcifying nested stromal-epithelial tumour (CNSET) are recently described entities with similar morphology, immunohistochemistry and molecular genetics. These are rare entities with only three large case series described till date. These tumours commonly present in the paediatric age group. NSETs, in addition have been described to be associated with ectopic adrenocorticotropic hormone (ACTH) production and Cushingoid features. It is important to discuss this rare group of tumours with a low malignant potential as the most common radiological differential diagnosis is hepatoblastoma, which has a relatively poorer prognosis. Thus, a pathologist needs to keep this entity in mind, so as to offer a correct histological diagnosis.

  4. Disruption of Vps4 and JNK Function in Drosophila Causes Tumour Growth

    PubMed Central

    Rodahl, Lina M.; Haglund, Kaisa; Sem-Jacobsen, Catherine; Wendler, Franz; Vincent, Jean-Paul; Lindmo, Karine; Rusten, Tor Erik; Stenmark, Harald

    2009-01-01

    Several regulators of endocytic trafficking have recently been identified as tumour suppressors in Drosophila. These include components of the endosomal sorting complex required for transport (ESCRT) machinery. Disruption of subunits of ESCRT-I and –II leads to cell-autonomous endosomal accumulation of ubiquitinated receptors, loss of apicobasal polarity and epithelial integrity, and increased cell death. Here we report that disruption of the ATPase dVps4, the most downstream component of the ESCRT machinery, causes the same array of cellular phenotypes. We find that loss of epithelial integrity and increased apoptosis, but not loss of cell polarity, require the activation of JNK signalling. Abrogation of JNK signalling prevents apoptosis in dVps4 deficient cells. Indeed double deficiency in dVps4 and JNK signalling leads to the formation of neoplastic tumours. We conclude that dvps4 is a tumour suppressor in Drosophila and that JNK is central to the cell-autonomous phenotypes of ESCRT-deficient cells. PMID:19194501

  5. NPM1 Silencing Reduces Tumour Growth and MAPK Signalling in Prostate Cancer Cells

    PubMed Central

    Loubeau, Gaëlle; Boudra, Rafik; Maquaire, Sabrina; Lours-Calet, Corinne; Beaudoin, Claude; Verrelle, Pierre; Morel, Laurent

    2014-01-01

    The chaperone nucleophosmin (NPM1) is over-expressed in the epithelial compartment of prostate tumours compared to adjacent healthy epithelium and may represent one of the key actors that support the neoplastic phenotype of prostate adenocarcinoma cells. Yet, the mechanisms that underlie NPM1 mediated phenotype remain elusive in the prostate. To better understand NPM1 functions in prostate cancer cells, we sought to characterize its impact on prostate cancer cells behaviour and decipher the mechanisms by which it may act. Here we show that NPM1 favors prostate tumour cell migration, invasion and colony forming. Furthermore, knockdown of NPM1 leads to a decrease in the growth of LNCaP-derived tumours grafted in Nude mice in vivo. Such oncogenic-like properties are found in conjunction with a positive regulation of NPM1 on the ERK1/2 (Extracellular signal-Regulated Kinases 1/2) kinase phosphorylation in response to EGF (Epidermal Growth Factor) stimulus, which is critical for prostate cancer progression following the setting of an autonomous production of the growth factor. NPM1 could then be a target to switch off specifically ERK1/2 pathway activation in order to decrease or inhibit cancer cell growth and migration. PMID:24796332

  6. Disruption of the Vasopressin 1b Receptor Gene Impairs the Attack Component of Aggressive Behavior in Mice

    PubMed Central

    Wersinger, Scott R.; Caldwell, Heather K.; Christiansen, Matthew; Scott Young, W.

    2008-01-01

    Vasopressin affects behavior via its two brain receptors, the vasopressin 1a and vasopressin 1b receptors (Avpr1b). Recent work from our lab has shown that disruption of the Avpr1b gene reduces inter-male aggression and reduces social motivation. Here we further characterized the aggressive phenotype in Avpr1b −/− (knockout) mice. We tested maternal aggression and predatory behavior. We also analyzed the extent to which food deprivation and competition over food increases inter-male aggression. We quantified defensive behavior in Avpr1b −/− mice and later tested offensive aggression in these same mice. Our results show that attack behavior toward a conspecific is consistently reduced in Avpr1b −/− mice. Predatory behavior is normal, suggesting that the deficit is not due to a global inability to detect and attack stimuli. Food deprivation, competition for food, and previous experience increase aggression in both Avpr1b +/+ and −/− mice. However, in these circumstances the level of aggression seen in knockout mice is still less than that observed in wild-type mice. Defensive avoidance behaviors, such as boxing and fleeing, are largely intact in knockout mice. Avpr1b −/− mice do not display as many "retaliatory" attacks as the Avpr1b +/+ mice. Interestingly, when territorial aggression was measured following the defensive behavior testing, Avpr1b −/− mice typically show less initial aggressive behavior than wild-type mice, but do show a significant increase in aggression with repeated testing. These studies confirm that deficits in aggression in Avpr1b −/− mice are limited to aggressive behavior involving the attack of a conspecific. We hypothesize that Avpr1b plays an important role in the central processing that couples the detection and perception of social cues (which appears normal) with the appropriate behavioral response. PMID:17284170

  7. Photoperiod and aggression induce changes in ventral gland compounds exclusively in male Siberian hamsters.

    PubMed

    Rendon, Nikki M; Soini, Helena A; Scotti, Melissa-Ann L; Weigel, Ellen R; Novotny, Milos V; Demas, Gregory E

    2016-05-01

    Chemical communication is a critical component of social behavior as it facilitates social encounters, allows for evaluation of the social partner, defines territories and resources, and advertises information such as sex and physiological state of an animal. Odors provide a key source of information about the social environment to rodents; however, studies identifying chemical compounds have thus far focused primarily on few species, particularly the house mouse. Moreover, considerably less attention has been focused on how environmental factors, reproductive phenotype, and behavioral context alter these compounds outside of reproduction. We examined the effects of photoperiod, sex, and social context on chemical communication in the seasonally breeding Siberian hamster. We sampled ventral gland secretions in both male and female hamsters before and after an aggressive encounter and identified changes in a range of volatile compounds. Next, we investigated how photoperiod, reproductive phenotype, and aggression altered ventral gland volatile compound composition across the sexes. Males exhibited a more diverse chemical composition, more sex-specific volatiles, and showed higher levels of excretion compared to females. Individual volatiles were also differentially excreted across photoperiod and reproductive phenotype, as well as differentially altered in response to an aggressive encounter. Female volatile compound composition, in contrast, did not differ across photoperiods or in response to aggression. Collectively, these data contribute to a greater understanding of context-dependent changes in chemical communication in a seasonally breeding rodent.

  8. Photoperiod and aggression induce changes in ventral gland compounds exclusively in male Siberian hamsters.

    PubMed

    Rendon, Nikki M; Soini, Helena A; Scotti, Melissa-Ann L; Weigel, Ellen R; Novotny, Milos V; Demas, Gregory E

    2016-05-01

    Chemical communication is a critical component of social behavior as it facilitates social encounters, allows for evaluation of the social partner, defines territories and resources, and advertises information such as sex and physiological state of an animal. Odors provide a key source of information about the social environment to rodents; however, studies identifying chemical compounds have thus far focused primarily on few species, particularly the house mouse. Moreover, considerably less attention has been focused on how environmental factors, reproductive phenotype, and behavioral context alter these compounds outside of reproduction. We examined the effects of photoperiod, sex, and social context on chemical communication in the seasonally breeding Siberian hamster. We sampled ventral gland secretions in both male and female hamsters before and after an aggressive encounter and identified changes in a range of volatile compounds. Next, we investigated how photoperiod, reproductive phenotype, and aggression altered ventral gland volatile compound composition across the sexes. Males exhibited a more diverse chemical composition, more sex-specific volatiles, and showed higher levels of excretion compared to females. Individual volatiles were also differentially excreted across photoperiod and reproductive phenotype, as well as differentially altered in response to an aggressive encounter. Female volatile compound composition, in contrast, did not differ across photoperiods or in response to aggression. Collectively, these data contribute to a greater understanding of context-dependent changes in chemical communication in a seasonally breeding rodent. PMID:26944610

  9. BDNF restricted knockout mice as an animal model for aggression

    PubMed Central

    Ito, Wataru; Chehab, Mahmoud; Thakur, Siddarth; Li, Jiayang; Morozov, Alexei

    2011-01-01

    Mice with global deletion of one BDNF allele, or with forebrain-restricted deletion of both alleles show elevated aggression, but this phenotype is accompanied by other behavioral changes, including increases in anxiety and deficits in cognition. Here, we performed behavioral characterization of conditional BDNF knockout mice generated using a Cre recombinase driver line, KA1-Cre, which expresses Cre in few areas of brain: highly at hippocampal area CA3, moderately in dentate gyrus, cerebellum and facial nerve nucleus. The mutant animals exhibited elevated conspecific aggression and social dominance, but did not show changes in anxiety-like behaviors assessed using the elevated plus maze and open field test. There were no changes in depression like behaviors tested in the forced swim test, but small increase in immobility in the tail suspension test. In cognitive tasks, mutants showed normal social recognition and normal spatial and fear memory, but exhibited a deficit in object recognition. Thus, this knockout can serve as a robust model of BDNF-dependent aggression and object recognition deficiency. PMID:21255268

  10. [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

  11. [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.

  12. Tumour-specific CD4 T cells eradicate melanoma via indirect recognition of tumour-derived antigen.

    PubMed

    Shklovskaya, Elena; Terry, Alexandra M; Guy, Thomas V; Buckley, Adrian; Bolton, Holly A; Zhu, Erhua; Holst, Jeff; Fazekas de St. Groth, Barbara

    2016-07-01

    The importance of CD4 T cells in tumour immunity has been increasingly recognised, with recent reports describing robust CD4 T cell-dependent tumour control in mice whose immune-regulatory mechanisms have been disturbed by irradiation, chemotherapy, immunomodulatory therapy and/or constitutive immunodeficiency. Tumour control in such models has been attributed in large part to direct Major Histocompatibility Complex (MHC) class II-dependent CD4 T cell killing of tumour cells. To test whether CD4 T cells can eradicate tumours without directly killing tumour cells, we developed an animal model in which tumour-derived antigen could be presented to T-cell receptor (TCR)-transgenic CD4 T cells by host but not tumour MHC class II molecules. In I-E(+) mice bearing I-E(null) tumours, naive I-E-restricted CD4 T cells proliferated locally in tumour-draining lymph nodes after recognising tumour-derived antigen on migratory dendritic cells. In lymphopaenic but not immunosufficient hosts, CD4 T cells differentiated into polarised T helper type 1 (Th1) cells expressing interferon gamma (IFNγ), tumor necrosis factor alpha (TNFα) and interleukin (IL)-2 but little IL-17, and cleared established tumours. Tumour clearance was enhanced by higher TCR affinity for tumour antigen-MHC class II and was critically dependent on IFNγ, as demonstrated by early tumour escape in animals treated with an IFNγ blocking antibody. Thus, CD4 T cells and IFNγ can control tumour growth without direct T-cell killing of tumour cells, and without requiring additional adaptive immune cells such as CD8 T cells and B cells. Our results support a role for effective CD4 T cell-dependent tumour immunity against MHC class II-negative tumours. PMID:26837456

  13. Glutathione S-transferase isoenzymes in human tumours and tumour derived cell lines.

    PubMed Central

    Lewis, A. D.; Forrester, L. M.; Hayes, J. D.; Wareing, C. J.; Carmichael, J.; Harris, A. L.; Mooghen, M.; Wolf, C. R.

    1989-01-01

    An increasing body of evidence indicates that glutathione S-transferases play a role in the intrinsic and acquired resistance of tumours to anticancer drugs. In view of the wide use of tumour cell lines to understand the factors which confer either sensitivity or resistance to chemotherapeutic agents we have determined glutathione S-transferase (GST) activity and isozyme composition in nine human cell lines. These data have been compared with the values obtained in solid tumours. In most cases overall GST activity was higher in the tumours than in the cell lines. This was most pronounced for the breast tumour samples relative to MCF7 cell line. The pi class GST subunit was present at similar concentration in the cell lines and the tumours, and in most cases was the most abundant subunit present. The alpha and mu class GST were expressed in most of the cell lines but at much lower concentration than the pi class subunit. Also considerable variability particularly in the expression of the mu subunits was observed. This was also the case for the expression of these subunits in the solid tumour samples. The levels of these GSTs (when expressed) in the solid tumours was invariably higher than that observed in the cell lines. There are therefore several similarities but also some significant differences in GST expression in solid tumours and cell lines. Whether the differences are because expression is lost during the generation of the cell lines or whether it reflects the individuality of human tumours remains to be clearly established. Images Figure 2 Figure 4 PMID:2789940

  14. Targeting ALCAM in the cryo-treated tumour microenvironment successfully induces systemic anti-tumour immunity.

    PubMed

    Kudo-Saito, Chie; Fuwa, Takafumi; Kawakami, Yutaka

    2016-07-01

    Cryoablative treatment has been widely used for treating cancer. However, the therapeutic efficacies are still controversial. The molecular mechanisms of the cryo-induced immune responses, particularly underlying the ineffectiveness, remain to be fully elucidated. In this study, we identified a new molecular mechanism involved in the cryo failure. We used cryo-ineffective metastatic tumour models that murine melanoma B16-F10 cells were subcutaneously and intravenously implanted into C57BL/6 mice. When the subcutaneous tumours were treated cryoablation on day 7 after tumour implantation, cells expressing activated leucocyte cell adhesion molecule (ALCAM/CD166) were significantly expanded not only locally in the treated tumours but also systemically in spleen and bone marrow of the mice. The cryo-induced ALCAM(+) cells including CD45(-) mesenchymal stem/stromal cells, CD11b(+)Gr1(+) myeloid-derived suppressor cells, and CD4(+)Foxp3(+) regulatory T cells significantly suppressed interferon γ production and cytotoxicity of tumour-specific CD8(+) T cells via ALCAM expressed in these cells. This suggests that systemic expansion of the ALCAM(+) cells negatively switches host-immune directivity to the tumour-supportive mode. Intratumoural injection with anti-ALCAM blocking monoclonal antibody (mAb) following the cryo treatment systemically induced tumour-specific CD8(+) T cells with higher cytotoxic activities, resulting in suppression of tumour growth and metastasis in the cryo-resistant tumour models. These suggest that expansion of ALCAM(+) cells is a determinant of limiting the cryo efficacy. Further combination with an immune checkpoint inhibitor anti-CTLA4 mAb optimized the anti-tumour efficacy of the dual-combination therapy. Targeting ALCAM may be a promising strategy for overcoming the cryo ineffectiveness leading to the better practical use of cryoablation in clinical treatment of cancer.

  15. Improving tumour heterogeneity MRI assessment with histograms

    PubMed Central

    Just, N

    2014-01-01

    By definition, tumours are heterogeneous. They are defined by marked differences in cells, microenvironmental factors (oxygenation levels, pH, VEGF, VPF and TGF-α) metabolism, vasculature, structure and function that in turn translate into heterogeneous drug delivery and therapeutic outcome. Ways to estimate quantitatively tumour heterogeneity can improve drug discovery, treatment planning and therapeutic responses. It is therefore of paramount importance to have reliable and reproducible biomarkers of cancerous lesions' heterogeneity. During the past decade, the number of studies using histogram approaches increased drastically with various magnetic resonance imaging (MRI) techniques (DCE-MRI, DWI, SWI etc.) although information on tumour heterogeneity remains poorly exploited. This fact can be attributed to a poor knowledge of the available metrics and of their specific meaning as well as to the lack of literature references to standardised histogram methods with which surrogate markers of heterogeneity can be compared. This review highlights the current knowledge and critical advances needed to investigate and quantify tumour heterogeneity. The key role of imaging techniques and in particular the key role of MRI for an accurate investigation of tumour heterogeneity is reviewed with a particular emphasis on histogram approaches and derived methods. PMID:25268373

  16. Mast cells, angiogenesis, and tumour growth.

    PubMed

    Ribatti, Domenico; Crivellato, Enrico

    2012-01-01

    Accumulation of mast cells (MCs) in tumours was described by Ehrlich in his doctoral thesis. Since this early account, ample evidence has been provided highlighting participation of MCs to the inflammatory reaction that occurs in many clinical and experimental tumour settings. MCs are bone marrow-derived tissue-homing leukocytes that are endowed with a panoply of releasable mediators and surface receptors. These cells actively take part to innate and acquired immune reactions as well as to a series of fundamental functions such as angiogenesis, tissue repair, and tissue remodelling. The involvement of MCs in tumour development is debated. Although some evidence suggests that MCs can promote tumourigenesis and tumour progression, there are some clinical sets as well as experimental tumour models in which MCs seem to have functions that favour the host. One of the major issues linking MCs to cancer is the ability of these cells to release potent pro-angiogenic factors. This review will focus on the most recent acquisitions about this intriguing field of research. This article is part of a Special Issue entitled: Mast cells in inflammation.

  17. Giant malignant phyllodes tumour of breast.

    PubMed

    Krishnamoorthy, Ramakrishnan; Savasere, Thejas; Prabhuswamy, Vinod Kumar; Babu, Rajashekhara; Shivaswamy, Sadashivaiah

    2014-01-01

    The term phyllodes tumour includes lesions ranging from completely benign tumours to malignant sarcomas. Clinically phyllodes tumours are smooth, rounded, and usually painless multinodular lesions indistinguishable from fibroadenomas. Percentage of phyllodes tumour classified as malignant ranges from 23% to 50%. We report a case of second largest phyllodes tumour in a 35-year-old lady who presented with swelling of right breast since 6 months, initially small in size, that progressed gradually to present size. Examination revealed mass in the right breast measuring 36×32 cms with lobulated firm surface and weighing 10 kgs. Fine needle aspiration cytology was reported as borderline phyllodes; however core biopsy examination showed biphasic neoplasm with malignant stromal component. Simple mastectomy was done and specimen was sent for histopathological examination which confirmed the core biopsy report. Postoperatively the patient received chemotherapy and radiotherapy. The patient is on follow-up for a year and has not shown any evidence of metastasis or recurrence. PMID:25548696

  18. Neuroendoscopic management of pineal region tumours.

    PubMed

    Ferrer, E; Santamarta, D; Garcia-Fructuoso, G; Caral, L; Rumià, J

    1997-01-01

    The management of pineal tumours remains controversial. During 1994 we treated four consecutive adults (16-44 yrs) harbouring a pineal tumour with a neuroendoscopic procedure. All of them presented with hydrocephalus. Pre-operative workup included cranial computerized tomography (CT), craniospinal magnetic resonance imaging (MRI) and serum levels of biological tumour markers. The endoscopic procedure consisted of a third ventriculostomy followed by biopsy with a flexible, steerable neuroendoscope. Histological diagnosis was achieved in three patients who no longer required a shunt device. Recorded complications were: bleeding during ventriculostomy that prevented us from obtaining a good sample for biopsy, short-term memory loss that cleared over a two-week period, and transient increase of pre-operative hemiparesis. Complications and morbidity are emphasized so as to be avoided with further technical experience. Neuroendoscopy affords a minimally invasive way of reaching three objectives by one-step surgery in the management of pineal region lesions: 1) CSF sample for analysis of tumour markers. 2) Treatment of hydrocephalus by third ventriculostomy. 3) Several biopsy specimens can be obtained identifying tumours which will require further open surgery or adjuvant radiation and/or chemotherapy. PMID:9059706

  19. Epidemiological study of salivary gland tumours.

    PubMed

    Frade Gonzalez, C; Lozano Ramirez, A; Garcia Caballero, T; Labella Caballero, T

    1999-01-01

    Tumours located in the salivary glands form the most heterogeneous group in all human oncological pathology. They show various epidemiological, clinical and evolutionary characteristics which separate them from other neoplasms of the head and neck. In this paper, we have carried out a study on their epidemiological aspects, collecting 80 cases diagnosed in the ENT Service of the University Hospital Complex of Santiago over 17 years. The incidence was 1.22 cases per 100,000 inhabitants per year. The frequency was higher in males (58.75%) and in the 7th decade of age. A predominance was noticed in females under 40 years of age and in males over this age, but the differences were not statistically significant. The most frequent site was the parotid gland, and we could not find any case in the sublingual gland. In 52.5% of cases the tumour was benign, pleomorphic adenoma being the most prevalent. Among malignant tumours, the epidermoid carcinoma stood out in our series. The prevalence of benign tumours in females and of malignant tumours in males was clear, with significant differences. We compare our results with the data published in the literature.

  20. Comprehensive functional analysis of the tousled-like kinase 2 frequently amplified in aggressive luminal breast cancers

    PubMed Central

    Kim, Jin-Ah; Tan, Ying; Wang, Xian; Cao, Xixi; Veeraraghavan, Jamunarani; Liang, Yulong; Edwards, Dean P.; Huang, Shixia; Pan, Xuewen; Li, Kaiyi; Schiff, Rachel; Wang, Xiao-Song

    2016-01-01

    More aggressive and therapy-resistant oestrogen receptor (ER)-positive breast cancers remain a great clinical challenge. Here our integrative genomic analysis identifies tousled-like kinase 2 (TLK2) as a candidate kinase target frequently amplified in ∼10.5% of ER-positive breast tumours. The resulting overexpression of TLK2 is more significant in aggressive and advanced tumours, and correlates with worse clinical outcome regardless of endocrine therapy. Ectopic expression of TLK2 leads to enhanced aggressiveness in breast cancer cells, which may involve the EGFR/SRC/FAK signalling. Conversely, TLK2 inhibition selectively inhibits the growth of TLK2-high breast cancer cells, downregulates ERα, BCL2 and SKP2, impairs G1/S cell cycle progression, induces apoptosis and significantly improves progression-free survival in vivo. We identify two potential TLK2 inhibitors that could serve as backbones for future drug development. Together, amplification of the cell cycle kinase TLK2 presents an attractive genomic target for aggressive ER-positive breast cancers. PMID:27694828

  1. Tumour angiogenesis is reduced in the Tc1 mouse model of Down Syndrome

    PubMed Central

    Reynolds, Louise E.; Watson, Alan R.; Baker, Marianne; Jones, Tania A.; D’Amico, Gabriela; Robinson, Stephen D.; Joffre, Carine; Garrido-Urbani, Sarah; Rodriguez-Manzaneque, Juan Carlos; Martino-Echarri, Estefanía; Aurrand-Lions, Michel; Sheer, Denise; Dagna-Bricarelli, Franca; Nizetic, Dean; McCabe, Christopher J.; Turnell, Andrew S.; Kermorgant, Stephanie; Imhof, Beat A.; Adams, Ralf; Fisher, Elizabeth M.C.; Tybulewicz, Victor L. J.; Hart, Ian R.; Hodivala-Dilke, Kairbaan M.

    2012-01-01

    Down Syndrome (DS) is a genetic disorder caused by full or partial trisomy of chromosome 21. It occurs in approximately 1/750 live births and presents with many clinical phenotypes including a reduced incidence of solid tumours1,2. Recent work using the Ts65Dn model of DS, that has orthologs of approximately 50% of the genes on human chromosome 21 (Hsa21), has suggested that three copies of the ETS23 or Down Syndrome candidate region 1 (DSCR1) genes4 (a previously known suppressor of angiogenesis5,6) is sufficient to inhibit tumour growth. We have used the Tc1 transchromosomic mouse model of DS9 to dissect the contribution of extra copies of genes on Hsa21 to tumour angiogenesis. This mouse expresses approximately 81% of Hsa21 genes but not the human DSCR1 region (Supplementary Fig. 1). We transplanted B16F0 and Lewis Lung Carcinoma (LLC) tumour cells into Tc1 mice and showed that growth of these tumours was reduced substantially when compared to wild-type littermate controls. Furthermore, tumour angiogenesis was repressed significantly in Tc1 mice. In particular, in vitro and in vivo angiogenic responses to vascular endothelial growth factor (VEGF) were inhibited. Examination of the genes on the segment of Hsa21 in Tc1 mice identified putative anti-angiogenic genes (ADAMTS17,8 and ERG9) and novel endothelial cell-specific genes10, never shown before to be involved in angiogenesis (JAM-B11 and PTTG1IP) that, when overexpressed, are responsible for the inhibition of angiogenic responses to VEGF. Three copies of these genes within the stromal compartment reduced tumour angiogenesis providing an explanation for the reduced tumour growth in DS. Furthermore, we anticipate that, in addition to the candidate genes that we show to be involved in the repression of angiogenesis, the Tc1 mouse model of DS will likely allow for the identification of other endothelial-specific anti-angiogenic targets relevant to a broad spectrum of cancer patients. PMID:20535211

  2. [Intermediate phenotype of schizophrenia].

    PubMed

    Hashimoto, Ryota

    2013-04-01

    Genes are major contributors to schizophrenia. The intermediate phenotype concept represents a strategy for identifying risk genes for schizophrenia and for characterizing the neural systems affected by risk gene variants to elucidate quantitative, mechanistic aspects of brain function implicated in schizophrenia. Intermediate phenotypes are defined by being heritable, being able to measure quantitatively; being related to the disorder and its symptoms in the general population; being stable over time; showing increased expression in unaffected relatives of probands; and cosegregation with the disorder in families. Intermediate phenotypes in schizophrenia are neurocognition, neuroimaging, neurophysiology, etc. In this review, we present concept, recent work, and future perspective of intermediate phenotype.

  3. ZEB1 turns into a transcriptional activator by interacting with YAP1 in aggressive cancer types

    PubMed Central

    Lehmann, Waltraut; Mossmann, Dirk; Kleemann, Julia; Mock, Kerstin; Meisinger, Chris; Brummer, Tilman; Herr, Ricarda; Brabletz, Simone; Stemmler, Marc P.; Brabletz, Thomas

    2016-01-01

    Early dissemination, metastasis and therapy resistance are central hallmarks of aggressive cancer types and the leading cause of cancer-associated deaths. The EMT-inducing transcriptional repressor ZEB1 is a crucial stimulator of these processes, particularly by coupling the activation of cellular motility with stemness and survival properties. ZEB1 expression is associated with aggressive behaviour in many tumour types, but the potent effects cannot be solely explained by its proven function as a transcriptional repressor of epithelial genes. Here we describe a direct interaction of ZEB1 with the Hippo pathway effector YAP, but notably not with its paralogue TAZ. In consequence, ZEB1 switches its function to a transcriptional co-activator of a ‘common ZEB1/YAP target gene set', thereby linking two pathways with similar cancer promoting effects. This gene set is a predictor of poor survival, therapy resistance and increased metastatic risk in breast cancer, indicating the clinical relevance of our findings. PMID:26876920

  4. '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

  5. Pedunculated solitary fibrous tumours arising from the pleura.

    PubMed

    Poyraz, A; Kilic, D; Hatipoglu, A; Bakirci, T; Bilezikci, B

    2006-09-01

    Solitary fibrous tumour (SFT) is one of the rare tumours which arise from visceral pleura. Klemperer and Rabin first described SFT as a distinct clinical entity among primary pleural tumoUrs in 1931. Approximately 820 cases have been reported in literature to date. The management of patients with SFT is complete resection of the tumour and follow up of the patient to detect any possible late recurrence. In the present paper, we report two cases of pedunculated solitary fibrous tumours of the pleura that appeared as a wandering chest nodule to which surgical resection undertaken at our hospital. The aim is to summarise our experience in the management of solitary fibrous tumour.

  6. Salivary gland tumours in Zimbabwe: report of 282 cases.

    PubMed

    Chidzonga, M M; Lopez Perez, V M; Portilla-Alvarez, A L

    1995-08-01

    Tumours of the salivary glands are relatively uncommon. In a review of 282 black patients seen at Harare Central Hospital, Zimbabwe, the relative incidence of various tumour types and the age and sex distribution were similar to those reported in other series. There were more tumours of the minor salivary glands than in reported Western series. There were more tumours of the minor salivary glands than in reported Western series. Pain and rapid growth were significant in distinguishing malignant from benign tumours. Malignant tumours were more common in elderly than in young patients.

  7. [Parotid tumours. Only 31% of mixed tumours. In one hundred and seventy-five parotidectomies (author's transl)].

    PubMed

    Massoud, E; Tarabay, F

    1982-06-10

    This article reports on an analytical study into the etiological aspects of 175 parotidectomies carried out in the Lebanon. In comparing our results with the classical data, we reached a certain number of interesting conclusions. Our study confirms classical breakdown of parotid tumours with 80% benign and 20% malignant. We also confirm the rise in the incidence of malignancy in line with age, and its classical predominance in male patients. Classically, the benign tumours can be divided into 80% mixed tumours, 8% warthin, and 6 to 7% other rare tumours. Our data concerning this breakdown of benign tumours is very different. We found 31% of mixed tumours, which is in line with the figure given by A. Palva. We can therefore conclude that mixed tumours are not the most common form of benign parotid tumours and that the so-called rare tumours account for 69% benign tumours. They include hemangiomas, tubercles, salivary cysts, chronic parotidits and Warthin's tumours. Another difference between the conclusions of our study and classical data concern warthin tumours, which account fort 18% of cases as compared to only 6% in the classical data. We can therefore conclude that the so-called "rare benign tumours of the parotid" show a far higher incidence in our country than the classical 6%, and in fact come far closer to 50% of all cases of benign tumours.

  8. 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.

  9. Unusual presentation of a scrotal tumour

    PubMed Central

    Sarkar, Debashis; Parr, Nijel J

    2014-01-01

    A 59-year-old man had a wide excision of the right-sided scrotal cancer in the neck of the scrotum. On dissection it became apparent that the tumour had developed a blood supply from the right spermatic cord. Histology revealed G2T2 squamous cell carcinoma. A biopsy from an abnormal skin area from the opposite groin reported chronic folliculitis. He underwent an ultrasound scanning of the groin and fine-needle aspiration, which did not show any suspicious features. Follow-up CT of the abdomen and pelvis after 6 weeks did not show any evidence of intra-abdominal lymphadenopathy. Another CT has been arranged within the next 3 months to confirm that the spread of the tumour does not follow the pattern of a testicular tumour. PMID:24879734

  10. Insulin receptor activation in solitary fibrous tumours.

    PubMed

    Li, Y; Chang, Q; Rubin, B P; Fletcher, C D M; Morgan, T W; Mentzer, S J; Sugarbaker, D J; Fletcher, J A; Xiao, S

    2007-04-01

    Solitary fibrous tumours (SFTs) are known to overexpress insulin-like growth factor 2 (IGF-2). The down-stream oncogenic pathways of IGF-2, however, are not clear. Here we report uniform activation of the insulin receptor (IR) pathway in SFTs, which are mesenchymal tumours frequently associated with hypoglycaemia. Whereas the IR and its downstream signalling pathways were constitutively activated in SFTs, insulin-like growth factor 1 receptor (IGF-1R) was not expressed in these tumours. We also find that SFT cells secrete IGF-2 and proliferate in serum-free medium, consistent with an IGF-2/IR autocrine loop. The aetiological relevance of IGF-2 is supported by expression of IR-A, the IR isoform with high affinity for IGF-2, in all SFTs. Our studies suggest that IR activation plays an oncogenic role in SFTs.

  11. Unusual presentation of a scrotal tumour.

    PubMed

    Sarkar, Debashis; Parr, Nijel J

    2014-05-30

    A 59-year-old man had a wide excision of the right-sided scrotal cancer in the neck of the scrotum. On dissection it became apparent that the tumour had developed a blood supply from the right spermatic cord. Histology revealed G2T2 squamous cell carcinoma. A biopsy from an abnormal skin area from the opposite groin reported chronic folliculitis. He underwent an ultrasound scanning of the groin and fine-needle aspiration, which did not show any suspicious features. Follow-up CT of the abdomen and pelvis after 6 weeks did not show any evidence of intra-abdominal lymphadenopathy. Another CT has been arranged within the next 3 months to confirm that the spread of the tumour does not follow the pattern of a testicular tumour.

  12. Tumours of the foot and ankle.

    PubMed

    Khan, Zeeshan; Hussain, Shakir; Carter, Simon R

    2015-09-01

    Sarcomas are rare tumours and particularly rarer in the foot and ankle region. The complex anatomy of the foot and ankle makes it unique and hence poses a challenge to the surgeon for limb salvage surgery. Other lesions found in the foot and ankle region are benign bone and soft tissue tumours, metastasis and infection. The purpose of this article is to discuss the relevance of the complex anatomy of the foot and ankle in relation to tumours, clinical features, their general management principles and further discussion about some of the more common bone and soft tissue lesions. Discussion of every single bone and soft tissue lesion in the foot and ankle region is beyond the scope of this article.

  13. Tumour Angiogenesis and Angiogenic Inhibitors: A Review

    PubMed Central

    Yadav, Lalita; Puri, Naveen; Satpute, Pranali; Sharma, Vandana

    2015-01-01

    Angiogenesis is a complex process depending on the coordination of many regulators and there by activating angiogenic switch. Recent advances in understanding of angiogenic mechanism have lead to the development of several anti-angiogenic and anti-metastatic agents that use the strategy of regulation of angiogenic switch. Antiangiogenic therapy is a form of treatment not cure for cancer and represents a highly effective strategy for destroying tumour because vascular supply is the fundamental requirement for growth of tumour. Because of the quiescent nature of normal adult vasculature, angiogenic inhibitors are expected to confer a degree of specificity when compared to nonspecific modalities of chemo and radiotherapy, so it has the advantage of less toxicities, does not induce drug resistance and deliver a relatively non toxic, long term treatment of tumour. PMID:26266204

  14. A transgenic zebrafish model expressing KIT-D816V recapitulates features of aggressive systemic mastocytosis.

    PubMed

    Balci, Tugce B; Prykhozhij, Sergey V; Teh, Evelyn M; Da'as, Sahar I; McBride, Eileen; Liwski, Robert; Chute, Ian C; Leger, Daniel; Lewis, Stephen M; Berman, Jason N

    2014-10-01

    Systemic mastocytosis (SM) is a rare myeloproliferative disease without curative therapy. Despite clinical variability, the majority of patients harbour a KIT-D816V mutation, but efforts to inhibit mutant KIT with tyrosine kinase inhibitors have been unsatisfactory, indicating a need for new preclinical approaches to identify alternative targets and novel therapies in this disease. Murine models to date have been limited and do not fully recapitulate the most aggressive forms of SM. We describe the generation of a transgenic zebrafish model expressing the human KIT-D816V mutation. Adult fish demonstrate a myeloproliferative disease phenotype, including features of aggressive SM in haematopoeitic tissues and high expression levels of endopeptidases, consistent with SM patients. Transgenic embryos demonstrate a cell-cycle phenotype with corresponding expression changes in genes associated with DNA maintenance and repair, such as reduced dnmt1. In addition, epcam was consistently downregulated in both transgenic adults and embryos. Decreased embryonic epcam expression was associated with reduced neuromast numbers, providing a robust in vivo phenotypic readout for chemical screening in KIT-D816V-induced disease. This study represents the first zebrafish model of a mast cell disease with an aggressive adult phenotype and embryonic markers that could be exploited to screen for novel agents in SM.

  15. Brain tumour-associated status epilepticus.

    PubMed

    Goonawardena, Janindu; Marshman, Laurence A G; Drummond, Katharine J

    2015-01-01

    We have reviewed the scant literature on status epilepticus in patients with brain tumours. Patients with brain tumour-associated epilepsy (TAE) appear less likely to develop status epilepticus (TASE) than patients with epilepsy in the general population (EGP) are to develop status epilepticus (SEGP). TASE is associated with lesions in similar locations as TAE; in particular, the frontal lobes. However, in contrast to TAE, where seizures commence early in the course of the disease or at presentation, TASE is more likely to occur later in the disease course and herald tumour progression. In marked contrast to TAE, where epilepsy risk is inversely proportional to Word Health Organization tumour grade, TASE risk appears to be directly proportional to tumour grade (high grade gliomas appear singularly predisposed). Whilst anti-epileptic drug (AED) resistance is more common in TAE than EGP (with resistance directly proportional to tumour grade and frontal location), TASE appears paradoxically more responsive to simple AED regimes than either TAE or SEGP. Although some results suggest that mortality may be higher with TASE than with SEGP, it is likely that (as with SEGP) the major determinant of mortality is the underlying disease process. Because all such data have been derived from retrospective studies, because TASE and SEGP are less common than TAE and EGP, and because TASE and SEGP classification has often been inconsistent, findings can only be considered preliminary: multi-centre, prospective studies are required. Whilst preliminary, our review suggests that TASE has a distinct clinical profile compared to TAE and SEGP. PMID:25150762

  16. Interspecific competition influences fitness benefits of assortative mating for territorial aggression in eastern bluebirds (Sialia sialis).

    PubMed

    Harris, Morgan R; Siefferman, Lynn

    2014-01-01

    Territorial aggression influences fitness and, in monogamous pairs, the behavior of both individuals could impact reproductive success. Moreover, territorial aggression is particularly important in the context of interspecific competition. Tree swallows and eastern bluebirds are highly aggressive, secondary cavity-nesting birds that compete for limited nesting sites. We studied eastern bluebirds at a field site in the southern Appalachian Mountains that has been recently colonized (<40 yr) by tree swallows undergoing a natural range expansion. The field site is composed of distinct areas where bluebirds compete regularly with tree swallows and areas where there is little interaction between the two species. Once birds had settled, we measured how interspecific competition affects the relationship between assortative mating (paired individuals that behave similarly) and reproductive success in eastern bluebirds. We found a strong tendency toward assortative mating throughout the field site. In areas of high interspecific competition, pairs that behaved the most similarly and displayed either extremely aggressive or extremely non-aggressive phenotypes experienced higher reproductive success. Our data suggest that interspecific competition with tree swallows may select for bluebirds that express similar behavior to that of their mate. Furthermore, animal personality may be an important factor influencing the outcome of interactions between native and aggressive, invasive species. PMID:24516672

  17. Increased aggressive and affiliative display behavior in intrauterine growth restricted (IUGR) baboons

    PubMed Central

    Huber, Hillary F; Ford, Susan M; Bartlett, Thad Q; Nathanielsz, Peter W

    2016-01-01

    Background We hypothesized intrauterine growth restricted offspring (IUGR) demonstrate higher rates of aggression and higher dominance ranks than control (CTR) offspring with normal weight at term; if aggressive behavior is advantageous during resource scarcity, developmental programming may lead to an association between aggression and IUGR. Methods We studied 22 group-housed baboons (ages 3-5 years). CTR (male n=8, female n=5) mothers ate ad libitum. IUGR (male n=4, female n=5) mothers were fed 70% feed eaten by CTR mothers during pregnancy and lactation. Results IUGR showed higher rates of aggressive displays (p<0.01) and friendly displays (p<0.02). Dominance ranks and physical aggression rates did not differ between groups. Conclusions High rates of IUGR aggressive display might reflect developmental programming of behavioral phenotypes enhancing fitness. Friendly displays may reflect reconciliation. Potential mechanisms include neurodevelopment and learning. Exploration of IUGR as a risk factor for behavioral patterns is important for developing diagnostic and therapeutic strategies. PMID:25891005

  18. Incidence, histopathologic analysis and distribution of tumours of the hand

    PubMed Central

    2014-01-01

    Background The aim of this large collective and meticulous study of primary bone tumours and tumourous lesions of the hand was to enhance the knowledge about findings of traumatological radiographs and improve differential diagnosis. Methods This retrospective study reviewed data collected from 1976 until 2006 in our Bone Tumour Registry. The following data was documented: age, sex, radiological investigations, tumour location, histopathological features including type and dignity of the tumour, and diagnosis. Results The retrospective analysis yielded 631 patients with a mean age of 35.9 ± 19.2 years. The majority of primary hand tumours were found in the phalanges (69.7%) followed by 24.7% in metacarpals and 5.6% in the carpals. Only 10.6% of all cases were malignant. The major lesion type was cartilage derived at 69.1%, followed by bone cysts 11.3% and osteogenic tumours 8.7%. The dominant tissue type found in phalanges and metacarpals was of cartilage origin. Osteogenic tumours were predominant in carpal bones. Enchondroma was the most commonly detected tumour in the hand (47.1%). Conclusions All primary skeletal tumours can be found in the hand and are most often of cartilage origin followed by bone cysts and osteogenic tumours. This study furthermore raises awareness about uncommon or rare tumours and helps clinicians to establish proper differential diagnosis, as the majority of detected tumours of the hand are asymptomatic and accidental findings on radiographs. PMID:24885007

  19. Sertoliform cystadenoma: a rare benign tumour of the rete testis

    PubMed Central

    2013-01-01

    Abstract Sertoliform cystadenoma of the rete testis represents an uncommon benign tumour. They appear in patients from 26 to 62 years of age. We describe a case of a 66-year-old man with a tumour in the area of the epididymal head. The tumour markers were not increased. Under the assumption of a malignant testicular tumour an inguinal orchiectomy was performed. The cut surface of this tumour was of grey/white color and showed small cysts. The tumour consisted of two compartments. The epithelial like tumour cells showed a sertoliform growth pattern and cystic dilatations. In between the tumour cells repeatedly actin expressing sclerotic areas could be recognized as the second tumour component. Proliferative activity was not increased. Immunohistochemically the tumour cells were positiv for inhibin, S-100, and CD 99. Alpha feto protein (AFP), human chorionic gonadotropin (ß-HCG) and placental alkaline phosphatase (PLAP) as well as synaptophysin, epithelial membrane antigene (EMA), and BCL-2 were not expressed. As far as we know this is the sixth reported case of this tumour. Because of the benign nature of this tumour the correct diagnosis is important for the intra- and postoperative management. Here we present a case of this rare tumour and discuss potential differential diagnosis. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1956026143857335 PMID:23406299

  20. 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

  1. Treatment of primary brain tumours in adults.

    PubMed

    McNamara, Shanne

    This article considers the complexities of caring for patients with primary brain tumours. The incidence, classification and clinical signs and symptoms are outlined. Adult patients experience disabling effects as a result of a brain tumour, which is often accompanied by high morbidity and mortality rates. The various treatment options available are summarised. However, for many patients, there are limited curative treatment options and the main focus is palliative care. The nurse's contribution to care and support of these patients and their families is discussed, with the aim of improving their quality of life.

  2. Stochastic Gompertz model of tumour cell growth.

    PubMed

    Lo, C F

    2007-09-21

    In this communication, based upon the deterministic Gompertz law of cell growth, a stochastic model in tumour growth is proposed. This model takes account of both cell fission and mortality too. The corresponding density function of the size of the tumour cells obeys a functional Fokker--Planck equation which can be solved analytically. It is found that the density function exhibits an interesting "multi-peak" structure generated by cell fission as time evolves. Within this framework the action of therapy is also examined by simply incorporating a therapy term into the deterministic cell growth term.

  3. Metastatic colonization by circulating tumour cells.

    PubMed

    Massagué, Joan; Obenauf, Anna C

    2016-01-21

    Metastasis is the main cause of death in people with cancer. To colonize distant organs, circulating tumour cells must overcome many obstacles through mechanisms that we are only now starting to understand. These include infiltrating distant tissue, evading immune defences, adapting to supportive niches, surviving as latent tumour-initiating seeds and eventually breaking out to replace the host tissue. They make metastasis a highly inefficient process. However, once metastases have been established, current treatments frequently fail to provide durable responses. An improved understanding of the mechanistic determinants of such colonization is needed to better prevent and treat metastatic cancer.

  4. Coordinated regulation of myeloid cells by tumours.

    PubMed

    Gabrilovich, Dmitry I; Ostrand-Rosenberg, Suzanne; Bronte, Vincenzo

    2012-03-22

    Myeloid cells are the most abundant nucleated haematopoietic cells in the human body and are a collection of distinct cell populations with many diverse functions. The three groups of terminally differentiated myeloid cells - macrophages, dendritic cells and granulocytes - are essential for the normal function of both the innate and adaptive immune systems. Mounting evidence indicates that the tumour microenvironment alters myeloid cells and can convert them into potent immunosuppressive cells. Here, we consider myeloid cells as an intricately connected, complex, single system and we focus on how tumours manipulate the myeloid system to evade the host immune response.

  5. A Large Extragnathic Keratocystic Odontogenic Tumour

    PubMed Central

    Bavle, Radhika M.; Muniswamappa, Sudhakara; Narasimhamurthy, Srinath

    2015-01-01

    Odontogenic keratocysts (OKCs) are developmental cysts which occur typically in the jawbones. They present more commonly in the posterior mandible of young adults than the maxilla. OKCs have been reclassified under odontogenic tumours in 2005 by the WHO and have since been termed as keratocystic odontogenic tumours (KCOTs). Here we report a case of a recurrent buccal lesion in a 62-year-old man which was provisionally diagnosed as a space infection (buccal abscess) but surprisingly turned out to be a soft tissue KCOT in an unusual location on histopathologic examination. PMID:26770859

  6. Phenotype definition in epilepsy.

    PubMed

    Winawer, Melodie R

    2006-05-01

    Phenotype definition consists of the use of epidemiologic, biological, molecular, or computational methods to systematically select features of a disorder that might result from distinct genetic influences. By carefully defining the target phenotype, or dividing the sample by phenotypic characteristics, we can hope to narrow the range of genes that influence risk for the trait in the study population, thereby increasing the likelihood of finding them. In this article, fundamental issues that arise in phenotyping in epilepsy and other disorders are reviewed, and factors complicating genotype-phenotype correlation are discussed. Methods of data collection, analysis, and interpretation are addressed, focusing on epidemiologic studies. With this foundation in place, the epilepsy subtypes and clinical features that appear to have a genetic basis are described, and the epidemiologic studies that have provided evidence for the heritability of these phenotypic characteristics, supporting their use in future genetic investigations, are reviewed. Finally, several molecular approaches to phenotype definition are discussed, in which the molecular defect, rather than the clinical phenotype, is used as a starting point.

  7. Solitary fibrous tumour: clinicopathological, immunohistochemical, and ultrastructural analysis of 12 cases arising in soft tissues, nasal cavity and nasopharynx, urinary bladder and prostate.

    PubMed

    Mentzel, T; Bainbridge, T C; Katenkamp, D

    1997-06-01

    The clinicopathological features of 12 extraserosal solitary fibrous tumours (SFT) are described. The age of the patients ranged from 18 to 72 years (mean: 48.2 years; median: 54 years); 5 were female patients. Seven lesions arose in soft tissue (5 in perifascial, and 1 each in subcutaneous and intramuscular tissues). They were situated in the groin (2 cases) and the neck, right buttock, left scapula, upper arm, and anterior abdominal wall (1 case each). One polypoid lesion was seen in in the nasal cavity and 1 in the nasopharynx; 2 neoplasms arose in the urinary bladder and 1 was located in the prostate and periprostatic tissue. Nine lesions were excised; in 1 patient wide excision was performed and in 2 patients, transurethral resection. Limited follow-up of 3 cases revealed a benign clinical course. The size of the neoplasms ranged from 1.7 cm to 20.0 cm (mean: 5.4 cm; median: 3.5 cm). Histologically, the neoplasms were well circumscribed and composed of cytologically bland spindle cells arranged without an obvious pattern; focally storiform or fascicular growth patterns were seen. Tumour cells were separated by thick bands of collagen demonstrating foci of keloid-like hyalinization. Prominent vascularity showing a haemangiopericytoma-like vascular pattern and vessels with thick, hyalinized vessel walls were seen in all cases. Increased mitotic activity was noted in 2 soft tissue cases (4-6 mitoses in 10 high-power fields); the other cases showed fewer than 2 mitotic figures in 10 highpower fields. Immunohistochemically, all cases tested stained positively for vimentin, CD34 and CD99, and 2 cases showed focal myofibroblastic differentiation. Two cases examined ultrastructurally showed a fibroblastic phenotype; focally pinocytic vesicles and microfilaments were identified. SFT represents a distinct neoplasm that should be included in the differential diagnosis of spindle-cell neoplasms in soft tissue, nasal cavity and nasopharynx, urinary bladder, and prostate

  8. Hypoxia-induced nitric oxide production and tumour perfusion is inhibited by pegylated arginine deiminase (ADI-PEG20)

    PubMed Central

    Burrows, Natalie; Cane, Gaelle; Robson, Mathew; Gaude, Edoardo; J. Howat, William; Szlosarek, Peter W.; Pedley, R. Barbara; Frezza, Christian; Ashcroft, Margaret; Maxwell, Patrick H.

    2016-01-01

    The hypoxic tumour microenvironment represents an aggressive, therapy-resistant compartment. As arginine is required for specific hypoxia-induced processes, we hypothesised that arginine-deprivation therapy may be useful in targeting hypoxic cancer cells. We explored the effects of the arginine-degrading agent ADI-PEG20 on hypoxia-inducible factor (HIF) activation, the hypoxia-induced nitric oxide (NO) pathway and proliferation using HCT116 and UMUC3 cells and xenografts. The latter lack argininosuccinate synthetase (ASS1) making them auxotrophic for arginine. In HCT116 cells, ADI-PEG20 inhibited hypoxic-activation of HIF-1α and HIF-2α, leading to decreased inducible-nitric oxide synthase (iNOS), NO-production, and VEGF. Interestingly, combining hypoxia and ADI-PEG20 synergistically inhibited ASS1. ADI-PEG20 inhibited mTORC1 and activated the unfolded protein response providing a mechanism for inhibition of HIF and ASS1. ADI-PEG20 inhibited tumour growth, impaired hypoxia-associated NO-production, and decreased vascular perfusion. Expression of HIF-1α/HIF-2α/iNOS and VEGF were reduced, despite an increased hypoxic tumour fraction. Similar effects were observed in UMUC3 xenografts. In summary, ADI-PEG20 inhibits HIF-activated processes in two tumour models with widely different arginine biology. Thus, ADI-PEG20 may be useful in the clinic to target therapy-resistant hypoxic cells in ASS1-proficient tumours and ASS1-deficient tumours. PMID:26972697

  9. Brain-derived neurotrophic factor (BDNF) and its precursor (proBDNF) in genetically defined fear-induced aggression.

    PubMed

    Ilchibaeva, Tatiana V; Kondaurova, Elena M; Tsybko, Anton S; Kozhemyakina, Rimma V; Popova, Nina K; Naumenko, Vladimir S

    2015-09-01

    The brain-derived neurotrophic factor (BDNF), its precursor (proBDNF) and BDNF mRNA levels were studied in the brain of wild rats selectively bred for more than 70 generations for either high level or for the lack of affective aggressiveness towards man. Significant increase of BDNF mRNA level in the frontal cortex and increase of BDNF level in the hippocampus of aggressive rats was revealed. In the midbrain and hippocampus of aggressive rats proBDNF level was increased, whereas BDNF/proBDNF ratio was reduced suggesting the prevalence and increased influence of proBDNF in highly aggressive rats. In the frontal cortex, proBDNF level in aggressive rats was decreased. Thus, considerable structure-specific differences in BDNF and proBDNF levels as well as in BDNF gene expression between highly aggressive and nonaggressive rats were shown. The data suggested the implication of BDNF and its precursor proBDNF in the mechanism of aggressiveness and in the creation of either aggressive or nonaggressive phenotype.

  10. Non-genetic cancer cell plasticity and therapy-induced stemness in tumour relapse: 'What does not kill me strengthens me'.

    PubMed

    Pisco, A O; Huang, S

    2015-05-26

    Therapy resistance and tumour relapse after drug therapy are commonly explained by Darwinian selection of pre-existing drug-resistant, often stem-like cancer cells resulting from random mutations. However, the ubiquitous non-genetic heterogeneity and plasticity of tumour cell phenotype raises the question: are mutations really necessary and sufficient to promote cell phenotype changes during tumour progression? Cancer therapy inevitably spares some cancer cells, even in the absence of resistant mutants. Accumulating observations suggest that the non-killed, residual tumour cells actively acquire a new phenotype simply by exploiting their developmental potential. These surviving cells are stressed by the cytotoxic treatment, and owing to phenotype plasticity, exhibit a variety of responses. Some are pushed into nearby, latent attractor states of the gene regulatory network which resemble evolutionary ancient or early developmental gene expression programs that confer stemness and resilience. By entering such stem-like, stress-response states, the surviving cells strengthen their capacity to cope with future noxious agents. Considering non-genetic cell state dynamics and the relative ease with which surviving but stressed cells can be tipped into latent attractors provides a foundation for exploring new therapeutic approaches that seek not only to kill cancer cells but also to avoid promoting resistance and relapse that are inherently linked to the attempts to kill them.

  11. Dopamine and serotonin signaling during two sensitive developmental periods differentially impact adult aggressive and affective behaviors in mice

    PubMed Central

    Yu, Qinghui; Teixeira, Cátia M.; Mahadevia, Darshini; Huang, Yung-Yu; Balsam, Daniel; Mann, J John; Gingrich, Jay A; Ansorge, Mark S.

    2014-01-01

    Pharmacologic blockade of monoamine oxidase A (MAOA) or serotonin transporter (5-HTT) has antidepressant and anxiolytic efficacy in adulthood. Yet, genetically conferred MAOA or 5-HTT hypo-activity is associated with altered aggression and increased anxiety/depression. Here we test the hypothesis that increased monoamine signaling during development causes these paradoxical aggressive and affective phenotypes. We find that pharmacologic MAOA blockade during early postnatal development (P2-P21) but not during peri-adolescence (P22-41) increases anxiety- and depression-like behavior in adult (> P90) mice, mimicking the effect of P2-21 5-HTT inhibition. Moreover, MAOA blockade during peri-adolescence, but not P2-21 or P182-201, increases adult aggressive behavior, and 5-HTT blockade from P22-P41 reduced adult aggression. Blockade of the dopamine transporter, but not the norepinephrine transporter, during P22-41 also increases adult aggressive behavior. Thus, P2-21 is a sensitive period during which 5-HT modulates adult anxiety/depression-like behavior, and P22-41 is a sensitive period during which DA and 5-HT bi-directionally modulate adult aggression. Permanently altered DAergic function as a consequence of increased P22-P41 monoamine signaling might underlie altered aggression. In support of this hypothesis, we find altered aggression correlating positively with locomotor response to amphetamine challenge in adulthood. Proving that altered DA function and aggression are causally linked, we demonstrate that optogenetic activation of VTA DAergic neurons increases aggression. It therefore appears that genetic and pharmacologic factors impacting dopamine and serotonin signaling during sensitive developmental periods can modulate adult monoaminergic function and thereby alter risk for aggressive and emotional dysfunction. PMID:24589889

  12. Phenotype heterogeneity in cancer cell populations

    NASA Astrophysics Data System (ADS)

    Almeida, Luis; Chisholm, Rebecca; Clairambault, Jean; Escargueil, Alexandre; Lorenzi, Tommaso; Lorz, Alexander; Trélat, Emmanuel

    2016-06-01

    Phenotype heterogeneity in cancer cell populations, be it of genetic, epigenetic or stochastic origin, has been identified as a main source of resistance to drug treatments and a major source of therapeutic failures in cancers. The molecular mechanisms of drug resistance are partly understood at the single cell level (e.g., overexpression of ABC transporters or of detoxication enzymes), but poorly predictable in tumours, where they are hypothesised to rely on heterogeneity at the cell population scale, which is thus the right level to describe cancer growth and optimise its control by therapeutic strategies in the clinic. We review a few results from the biological literature on the subject, and from mathematical models that have been published to predict and control evolution towards drug resistance in cancer cell populations. We propose, based on the latter, optimisation strategies of combined treatments to limit emergence of drug resistance to cytotoxic drugs in cancer cell populations, in the monoclonal situation, which limited as it is still retains consistent features of cell population heterogeneity. The polyclonal situation, that may be understood as "bet hedging" of the tumour, thus protecting itself from different sources of drug insults, may lie beyond such strategies and will need further developments. In the monoclonal situation, we have designed an optimised therapeutic strategy relying on a scheduled combination of cytotoxic and cytostatic treatments that can be adapted to different situations of cancer treatments. Finally, we review arguments for biological theoretical frameworks proposed at different time and development scales, the so-called atavistic model (diachronic view relying on Darwinian genotype selection in the coursof billions of years) and the Waddington-like epigenetic landscape endowed with evolutionary quasi-potential (synchronic view relying on Lamarckian phenotype instruction of a given genome by reversible mechanisms), to

  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. Ovarian hilus-cell tumour: a case report.

    PubMed

    Georgiev, T N; Valkov, I M; Dokumov, S I

    1980-01-01

    A case of hilus-cell tumour of the ovary, associated with polycystic ovarian disease is reported. The authors discuss the data from hormonal investigations, the morphological picture and the genesis of the tumour.

  18. Intraoperative intravital microscopy permits the study of human tumour vessels

    PubMed Central

    Fisher, Daniel T.; Muhitch, Jason B.; Kim, Minhyung; Doyen, Kurt C.; Bogner, Paul N.; Evans, Sharon S.; Skitzki, Joseph J.

    2016-01-01

    Tumour vessels have been studied extensively as they are critical sites for drug delivery, anti-angiogenic therapies and immunotherapy. As a preclinical tool, intravital microscopy (IVM) allows for in vivo real-time direct observation of vessels at the cellular level. However, to date there are no reports of intravital high-resolution imaging of human tumours in the clinical setting. Here we report the feasibility of IVM examinations of human malignant disease with an emphasis on tumour vasculature as the major site of tumour-host interactions. Consistent with preclinical observations, we show that patient tumour vessels are disorganized, tortuous and ∼50% do not support blood flow. Human tumour vessel diameters are larger than predicted from immunohistochemistry or preclinical IVM, and thereby have lower wall shear stress, which influences delivery of drugs and cellular immunotherapies. Thus, real-time clinical imaging of living human tumours is feasible and allows for detection of characteristics within the tumour microenvironment. PMID:26883450

  19. Brain tumour cells interconnect to a functional and resistant network.

    PubMed

    Osswald, Matthias; Jung, Erik; Sahm, Felix; Solecki, Gergely; Venkataramani, Varun; Blaes, Jonas; Weil, Sophie; Horstmann, Heinz; Wiestler, Benedikt; Syed, Mustafa; Huang, Lulu; Ratliff, Miriam; Karimian Jazi, Kianush; Kurz, Felix T; Schmenger, Torsten; Lemke, Dieter; Gömmel, Miriam; Pauli, Martin; Liao, Yunxiang; Häring, Peter; Pusch, Stefan; Herl, Verena; Steinhäuser, Christian; Krunic, Damir; Jarahian, Mostafa; Miletic, Hrvoje; Berghoff, Anna S; Griesbeck, Oliver; Kalamakis, Georgios; Garaschuk, Olga; Preusser, Matthias; Weiss, Samuel; Liu, Haikun; Heiland, Sabine; Platten, Michael; Huber, Peter E; Kuner, Thomas; von Deimling, Andreas; Wick, Wolfgang; Winkler, Frank

    2015-12-01

    Astrocytic brain tumours, including glioblastomas, are incurable neoplasms characterized by diffusely infiltrative growth. Here we show that many tumour cells in astrocytomas extend ultra-long membrane protrusions, and use these distinct tumour microtubes as routes for brain invasion, proliferation, and to interconnect over long distances. The resulting network allows multicellular communication through microtube-associated gap junctions. When damage to the network occurred, tumour microtubes were used for repair. Moreover, the microtube-connected astrocytoma cells, but not those remaining unconnected throughout tumour progression, were protected from cell death inflicted by radiotherapy. The neuronal growth-associated protein 43 was important for microtube formation and function, and drove microtube-dependent tumour cell invasion, proliferation, interconnection, and radioresistance. Oligodendroglial brain tumours were deficient in this mechanism. In summary, astrocytomas can develop functional multicellular network structures. Disconnection of astrocytoma cells by targeting their tumour microtubes emerges as a new principle to reduce the treatment resistance of this disease.

  20. Cutaneous location of atypical teratoid/rhabdoid tumour.

    PubMed

    Bellon, Nathalia; Fraitag, Sylvie; Miquel, Catherine; Salomon, Laurent J; Bourdeaut, Franck; Bodemer, Christine; Roujeau, Thomas; Zerah, Michel; Hadj-Rabia, Smail

    2014-07-01

    Atypical teratoid/rhabdoid tumour is a rare and highly malignant tumour of the posterior fossae nervous system that occurs in children especially in the first few years of life. Cutaneous location is not previously reported. A newborn boy was referred for both aqueductal stenosis detected antenatally and skin tags mimicking hamartoma. The cerebral tumour increased in size during a few months leading to both skin and cerebral biopsies. Integrase Interactor-1 (INI-1) immunostaining and tumoural and leukocytes INI-1 gene sequencing confirmed the atypical teratoid/rhabdoid tumour nature of the cerebral tumour. INI-1 immunostaining in skin biopsy confirmed the dermal location of rhabdoid tumour. Thus, unusual cutaneous lesions may be part of atypical teratoid/rhabdoid tumour. The loss of Integrase INI-1 on immunohistochemical staining is characteristic.

  1. Intraoperative intravital microscopy permits the study of human tumour vessels.

    PubMed

    Fisher, Daniel T; Muhitch, Jason B; Kim, Minhyung; Doyen, Kurt C; Bogner, Paul N; Evans, Sharon S; Skitzki, Joseph J

    2016-02-17

    Tumour vessels have been studied extensively as they are critical sites for drug delivery, anti-angiogenic therapies and immunotherapy. As a preclinical tool, intravital microscopy (IVM) allows for in vivo real-time direct observation of vessels at the cellular level. However, to date there are no reports of intravital high-resolution imaging of human tumours in the clinical setting. Here we report the feasibility of IVM examinations of human malignant disease with an emphasis on tumour vasculature as the major site of tumour-host interactions. Consistent with preclinical observations, we show that patient tumour vessels are disorganized, tortuous and ∼50% do not support blood flow. Human tumour vessel diameters are larger than predicted from immunohistochemistry or preclinical IVM, and thereby have lower wall shear stress, which influences delivery of drugs and cellular immunotherapies. Thus, real-time clinical imaging of living human tumours is feasible and allows for detection of characteristics within the tumour microenvironment.

  2. Benign metastatic mixed tumours or unrecognized salivary carcinomas?

    PubMed

    el-Naggar, A; Batsakis, J G; Kessler, S

    1988-09-01

    'Benign metastasizing mixed tumours' are enigmatic lesions of the parotid gland. The authors, through the illustrations of a case and review of the literature, conclude that the tumours are unrecognized and currently unclassified malignancies.

  3. Integration of tumour and viral genomic characterisations in HBV-related hepatocellular carcinomas

    PubMed Central

    Amaddeo, Giuliana; Cao, Qian; Ladeiro, Yannick; Imbeaud, Sandrine; Nault, Jean-Charles; Jaoui, Daphne; Gaston Mathe, Yann; Laurent, Christophe; Laurent, Alexis; Bioulac-Sage, Paulette; Calderaro, Julien; Zucman-Rossi, Jessica

    2015-01-01

    Background and aim Hepatocellular carcinoma (HCC) is the most common liver cancer. We characterised HCC associated with infection compared with non-HBV-related HCC to understand interactions between viral and hepatocyte genomic alterations and their relationships with clinical features. Methods Frozen HBV (n=86) or non-HBV-related (n=90) HCC were collected in two French surgical departments. Viral characterisation was performed by sequencing HBS and HBX genes and quantifying HBV DNA and cccDNA. Nine genes were screened for somatic mutations and expression profiling of 37 genes involved in hepatocarcinogenesis was studied. Results HBX revealed frequent non-sense, frameshift and deletions in tumours, suggesting an HBX inactivation selected in HCC. The number of viral copies was frequently lower in tumour than in non-tumour tissues (p=0.0005) and patients with low HBV copies in the non-tumour liver tissues presented additional risk factor (HCV, alcohol or non-alcoholic steato-hepatitis, p=0.006). P53 was the most frequently altered pathway in HBV-related HCC (47%, p=0.001). Furthermore, TP53 mutations were associated with shorter survival only in HBV-related HCC (p=0.02) whereas R249S mutations were identified exclusively in migrants. Compared with other aetiologies, HBV-HCC were more frequently classified in tumours subgroups with upregulation of genes involved in cell-cycle regulation and a progenitor phenotype. Finally, in HBV-related HCC, transcriptomic profiles were associated with specific gene mutations (HBX, TP53, IRF2, AXIN1 and CTNNB1). Conclusions Integrated genomic characterisation of HBV and non-HBV-related HCC emphasised the immense molecular diversity of HCC closely related to aetiologies that could impact clinical care of HCC patients. PMID:25021421

  4. Induction of haem oxygenase-1 by nitric oxide and ischaemia in experimental solid tumours and implications for tumour growth

    PubMed Central

    Doi, K; Akaike, T; Fujii, S; Tanaka, S; Ikebe, N; Beppu, T; Shibahara, S; Ogawa, M; Maeda, H

    1999-01-01

    Induction of haem oxygenase-1 (HO-1) as well as nitric oxide (NO) biosynthesis during tumour growth was investigated in an experimental solid tumour model (AH136B hepatoma) in rats. An immunohistochemical study showed that the inducible isoform of NO synthase (iNOS) was localized in monocyte-derived macrophages, which infiltrated interstitial spaces of solid tumour, but not in the tumour cells. Excessive production of NO in the tumour tissue was unequivocally verified by electron spin resonance spectroscopy. Tumour growth was moderately suppressed by treatment with either Nω-nitro-L-arginine methyl ester (L-NAME) or S-methylisothiourea sulphate (SMT). In contrast, HO-1 was found only in tumour cells, not in macrophages, by in situ hybridization for HO-1 mRNA. HO-1 expression in AH136B cells in culture was strongly enhanced by an NO (NO+) donor S-nitroso-N-acetyl penicillamine. HO-1 mRNA expression in the solid tumour in vivo decreased significantly after treatment with low doses of NOS inhibitors such as L-NAME and SMT (6–20 mg kg−1). However, the level of HO-1 mRNA in the solid tumour treated with higher doses of NOS inhibitor was similar to that of the solid tumour without NOS inhibitor treatment. Strong induction of HO-1 was also observed in solid tumours after occlusion or embolization of the tumour-feeding artery, indicating that ischaemic stress which may involve oxidative stress triggers HO-1 induction in the solid tumour. Lastly, it is of great importance that an HO inhibitor, zinc protoporphyrin IX injected intra-arterially to the solid tumour suppressed the tumour growth to a great extent. In conclusion, HO-1 expression in the solid tumour may confer resistance of tumour cells to hypoxic stress as well as to NO-mediated cytotoxicity. © 1999 Cancer Research Campaign PMID:10471043

  5. Edge effects in game-theoretic dynamics of spatially structured tumours.

    PubMed

    Kaznatcheev, Artem; Scott, Jacob G; Basanta, David

    2015-07-01

    Cancer dynamics are an evolutionary game between cellular phenotypes. A typical assumption in this modelling paradigm is that the probability of a given phenotypic strategy interacting with another depends exclusively on the abundance of those strategies without regard for local neighbourhood structure. We address this limitation by using the Ohtsuki-Nowak transform to introduce spatial structure to the go versus grow game. We show that spatial structure can promote the invasive (go) strategy. By considering the change in neighbourhood size at a static boundary--such as a blood vessel, organ capsule or basement membrane--we show an edge effect that allows a tumour without invasive phenotypes in the bulk to have a polyclonal boundary with invasive cells. We present an example of this promotion of invasive (epithelial-mesenchymal transition-positive) cells in a metastatic colony of prostate adenocarcinoma in bone marrow. Our results caution that pathologic analyses that do not distinguish between cells in the bulk and cells at a static edge of a tumour can underestimate the number of invasive cells. Although we concentrate on applications in mathematical oncology, we expect our approach to extend to other evolutionary game models where interaction neighbourhoods change at fixed system boundaries.

  6. Edge effects in game-theoretic dynamics of spatially structured tumours

    PubMed Central

    Kaznatcheev, Artem; Scott, Jacob G.; Basanta, David

    2015-01-01

    Cancer dynamics are an evolutionary game between cellular phenotypes. A typical assumption in this modelling paradigm is that the probability of a given phenotypic strategy interacting with another depends exclusively on the abundance of those strategies without regard for local neighbourhood structure. We address this limitation by using the Ohtsuki–Nowak transform to introduce spatial structure to the go versus grow game. We show that spatial structure can promote the invasive (go) strategy. By considering the change in neighbourhood size at a static boundary—such as a blood vessel, organ capsule or basement membrane—we show an edge effect that allows a tumour without invasive phenotypes in the bulk to have a polyclonal boundary with invasive cells. We present an example of this promotion of invasive (epithelial–mesenchymal transition-positive) cells in a metastatic colony of prostate adenocarcinoma in bone marrow. Our results caution that pathologic analyses that do not distinguish between cells in the bulk and cells at a static edge of a tumour can underestimate the number of invasive cells. Although we concentrate on applications in mathematical oncology, we expect our approach to extend to other evolutionary game models where interaction neighbourhoods change at fixed system boundaries. PMID:26040596

  7. MicroRNAs associated with small bowel neuroendocrine tumours and their metastases.

    PubMed

    Miller, Helen C; Frampton, Adam E; Malczewska, Anna; Ottaviani, Silvia; Stronach, Euan A; Flora, Rashpal; Kaemmerer, Daniel; Schwach, Gert; Pfragner, Roswitha; Faiz, Omar; Kos-Kudła, Beata; Hanna, George B; Stebbing, Justin; Castellano, Leandro; Frilling, Andrea

    2016-09-01

    Novel molecular analytes are needed in small bowel neuroendocrine tumours (SBNETs) to better determine disease aggressiveness and predict treatment response. In this study, we aimed to profile the global miRNome of SBNETs, and identify microRNAs (miRNAs) involved in tumour progression for use as potential biomarkers. Two independent miRNA profiling experiments were performed (n=90), including primary SBNETs (n=28), adjacent normal small bowel (NSB; n=14), matched lymph node (LN) metastases (n=24), normal LNs (n=7), normal liver (n=2) and liver metastases (n=15). We then evaluated potentially targeted genes by performing integrated computational analyses. We discovered 39 miRNAs significantly deregulated in SBNETs compared with adjacent NSB. The most upregulated (miR-204-5p, miR-7-5p and miR-375) were confirmed by qRT-PCR. Two miRNAs (miR-1 and miR-143-3p) were significantly downregulated in LN and liver metastases compared with primary tumours. Furthermore, we identified upregulated gene targets for miR-1 and miR-143-3p in an existing SBNET dataset, which could contribute to disease progression, and show that these miRNAs directly regulate FOSB and NUAK2 oncogenes. Our study represents the largest global miRNA profiling of SBNETs using matched primary tumour and metastatic samples. We revealed novel miRNAs deregulated during SBNET disease progression, and important miRNA-mRNA interactions. These miRNAs have the potential to act as biomarkers for patient stratification and may also be able to guide treatment decisions. Further experiments to define molecular mechanisms and validate these miRNAs in larger tissue cohorts and in biofluids are now warranted. PMID:27353039

  8. Cytoreductive surgery in disseminated non-seminomatous germ cell tumours of testis.

    PubMed

    Kulkarni, R P; Reynolds, K W; Newlands, E S; Dawson, P M; Makey, A R; Theodorou, N A; Bradley, J; Begent, R H; Rustin, G J; Bagshawe, K D

    1991-02-01

    Between 1977 and 1988, 67 patients underwent surgical removal of residual metastatic deposits following an aggressive chemotherapy regimen (cisplatin, vincristine, methotrexate and bleomycin alternating with etoposide, actinomycin D and cyclophosphamide) for disseminated germ cell tumours of the testis (stage IIB or above). Ninety-one surgical procedures were performed. There were 63 (69 per cent) retroperitoneal lymph node dissections, 16 (18 per cent) thoracotomies, three (3 per cent) hepatic resections, three (3 per cent) craniotomies, five (5 per cent) delayed orchidectomies and one anterolateral decompression of the vertebral column. Nine (13 per cent) patients required a repeat retroperitoneal node dissection and one patient needed a repeat thoracotomy to remove recurrent metastatic deposits during the period of follow-up. Multivisceral resections and vascular reconstruction procedures were required in 20 (30 per cent) patients undergoing retroperitoneal node dissection. Fifty-five (82 per cent) patients remain in complete remission with a mean follow-up period of 49.6 months (range 2-121 months). Nine (13 per cent) patients died with metastatic disease between 2 months to 4 years after operation. There were three deaths in the perioperative period (4 per cent). The histology of the resected metastases revealed undifferentiated active tumour in 20 (30 per cent) patients, differentiated mature teratoma in 29 (43 per cent) patients and fibrosis/necrosis in 18 (27 per cent) patients. Twelve (60 per cent) patients with undifferentiated elements and 15 patients (60 per cent) with raised preoperative tumour markers (poor prognostic categories) are in complete remission. Cytoreductive surgery in patients with metastatic germ cell tumours offers the best chance of remission following chemotherapy even in poor prognostic group categories.

  9. Prevention and treatment of colon cancer by peroral administration of HAMLET (human α-lactalbumin made lethal to tumour cells)

    PubMed Central

    Puthia, Manoj; Storm, Petter; Nadeem, Aftab; Hsiung, Sabrina; Svanborg, Catharina

    2014-01-01

    Background Most colon cancers start with dysregulated Wnt/β-catenin signalling and remain a major therapeutic challenge. Examining whether HAMLET (human α-lactalbumin made lethal to tumour cells) may be used for colon cancer treatment is logical, based on the properties of the complex and its biological context. Objective To investigate if HAMLET can be used for colon cancer treatment and prevention. ApcMin/+ mice, which carry mutations relevant to hereditary and sporadic human colorectal tumours, were used as a model for human disease. Method HAMLET was given perorally in therapeutic and prophylactic regimens. Tumour burden and animal survival of HAMLET-treated and sham-fed mice were compared. Tissue analysis focused on Wnt/β-catenin signalling, proliferation markers and gene expression, using microarrays, immunoblotting, immunohistochemistry and ELISA. Confocal microscopy, reporter assay, immunoprecipitation, immunoblotting, ion flux assays and holographic imaging were used to determine effects on colon cancer cells. Results Peroral HAMLET administration reduced tumour progression and mortality in ApcMin/+ mice. HAMLET accumulated specifically in tumour tissue, reduced β-catenin and related tumour markers. Gene expression analysis detected inhibition of Wnt signalling and a shift to a more differentiated phenotype. In colon cancer cells with APC mutations, HAMLET altered β-catenin integrity and localisation through an ion channel-dependent pathway, defining a new mechanism for controlling β-catenin signalling. Remarkably, supplying HAMLET to the drinking water from the time of weaning also significantly prevented tumour development. Conclusions These data identify HAMLET as a new, peroral agent for colon cancer prevention and treatment, especially needed in people carrying APC mutations, where colon cancer remains a leading cause of death. PMID:23348960

  10. A human tRNA methyltransferase 9-like protein prevents tumour growth by regulating LIN9 and HIF1-α.

    PubMed

    Begley, Ulrike; Sosa, Maria Soledad; Avivar-Valderas, Alvaro; Patil, Ashish; Endres, Lauren; Estrada, Yeriel; Chan, Clement T Y; Su, Dan; Dedon, Peter C; Aguirre-Ghiso, Julio A; Begley, Thomas

    2013-03-01

    Emerging evidence points to aberrant regulation of translation as a driver of cell transformation in cancer. Given the direct control of translation by tRNA modifications, tRNA modifying enzymes may function as regulators of cancer progression. Here, we show that a tRNA methyltransferase 9-like (hTRM9L/KIAA1456) mRNA is down-regulated in breast, bladder, colorectal, cervix and testicular carcinomas. In the aggressive SW620 and HCT116 colon carcinoma cell lines, hTRM9L is silenced and its re-expression and methyltransferase activity dramatically suppressed tumour growth in vivo. This growth inhibition was linked to decreased proliferation, senescence-like G0/G1-arrest and up-regulation of the RB interacting protein LIN9. Additionally, SW620 cells re-expressing hTRM9L did not respond to hypoxia via HIF1-α-dependent induction of GLUT1. Importantly, hTRM9L-negative tumours were highly sensitive to aminoglycoside antibiotics and this was associated with altered tRNA modification levels compared to antibiotic resistant hTRM9L-expressing SW620 cells. Our study links hTRM9L and tRNA modifications to inhibition of tumour growth via LIN9 and HIF1-α-dependent mechanisms. It also suggests that aminoglycoside antibiotics may be useful to treat hTRM9L-deficient tumours. PMID:23381944

  11. Biodegradable interstitial release polymer loading a novel small molecule targeting Axl receptor tyrosine kinase and reducing brain tumour migration and invasion.

    PubMed

    Yen, S-Y; Chen, S-R; Hsieh, J; Li, Y-S; Chuang, S-E; Chuang, H-M; Huang, M-H; Lin, S-Z; Harn, H-J; Chiou, T-W

    2016-04-28

    Glioblastoma multiforme (GBM) is the most common and aggressive brain tumour. The neoplasms are difficult to resect entirely because of their highly infiltration property and leading to the tumour edge is unclear. Gliadel wafer has been used as an intracerebral drug delivery system to eliminate the residual tumour. However, because of its local low concentration and short diffusion distance, patient survival improves non-significantly. Axl is an essential regulator in cancer metastasis and patient survival. In this study, we developed a controlled-release polyanhydride polymer loading a novel small molecule, n-butylidenephthalide (BP), which is not only increasing local drug concentration and extending its diffusion distance but also reducing tumour invasion, mediated by reducing Axl expression. First, we determined that BP inhibited the expression of Axl in a dose- and time-dependent manner and reduced the migratory and invasive capabilities of GBM cells. In addition, BP downregulated matrix metalloproteinase activity, which is involved in cancer cell invasion. Furthermore, we demonstrated that BP regulated Axl via the extracellular signal-regulated kinases pathway. Epithelial-to-mesenchymal transition (EMT) is related to epithelial cells in the invasive migratory mesenchymal cells that underlie cancer progression; we demonstrated that BP reduced the expression of EMT-related genes. Furthermore, we used the overexpression of Axl in GBM cells to prove that Axl is a crucial target in the inhibition of GBM EMT, migration and invasion. In an in vivo study, we demonstrated that BP inhibited tumour growth and suppressed Axl expression in a dose-dependent manner according to a subcutaneous tumour model. Most importantly, in an intracranial tumour model with BP wafer in situ treatment, we demonstrated that the BP wafer not only significantly increased the survival rate but also decreased Axl expression, and inhibited tumour invasion. These results contribute to the

  12. 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.

  13. [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

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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

  19. [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

  20. 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.