40 research outputs found
Timp1 interacts with beta-1 integrin and CD63 along melanoma genesis and confers anoikis resistance by activating PI3-K signaling pathway independently of Akt phosphorylation
Background: Anoikis resistance is one of the abilities acquired along tumor progression. This characteristic is associated with metastasis development, since tumorigenic cells must survive independently of cell-matrix interactions in this process. in our laboratory, it was developed a murine melanocyte malignant transformation model associated with a sustained stressful condition. After subjecting melan-a melanocytes to 1, 2, 3 and 4 cycles of anchorage impediment, anoikis resistant cells were established and named 1C, 2C, 3C and 4C, respectively. These cells showed altered morphology and PMA independent cell growth, but were not tumorigenic, corresponding to pre-malignant cells. After limiting dilution of 4C pre-malignant cells, melanoma cell lines with different characteristics were obtained. Previous data from our group showed that increased Timp1 expression correlated with anoikis-resistant phenotype. Timp1 was shown to confer anchorage-independent growth capability to melan-a melanocytes and render melanoma cells more aggressive when injected into mice. However, the mechanisms involved in anoikis regulation by Timp1 in tumorigenic cells are not clear yet.Methods: the beta 1-integrin and Timp1 expression were evaluated by Western blotting and CD63 protein expression by flow cytometry using specific antibodies. To analyze the interaction among Timp1, CD63 and beta 1-integrin, immunoprecipitation assays were performed, anoikis resistance capability was evaluated in the presence or not of the PI3-K inhibitors, Wortmannin and LY294002. Relative expression of TIMP1 and CD63 in human metastatic melanoma cells was analyzed by real time PCR.Results: Differential association among Timp1, CD63 and beta 1-integrins was observed in melan-a melanocytes, 4C pre-malignant melanocytes and 4C11- and 4C11+ melanoma cells. Timp1 present in conditioned medium of melanoma cells rendered melan-a melanocytes anoikis-resistant through PI3-K signaling pathway independently of Akt activation. in human melanoma cell lines, in which TIMP1 and beta-1 integrin were also found to be interacting, TIMP1 and CD63 levels together was shown to correlate significantly with colony formation capacity.Conclusions: Our results show that Timp1 is assembled in a supramolecular complex containing CD63 and beta 1-integrins along melanoma genesis and confers anoikis resistance by activating PI3-K signaling pathway, independently of Akt phosphorylation. in addition, our data point TIMP1, mainly together with CD63, as a potential biomarker of melanoma.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Dept Pharmacol, São Paulo, BrazilUniversidade Federal de São Paulo, Microbiol Immunol & Parasitol Dept, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem, São Paulo, BrazilLudwig Inst Canc Res, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, São Paulo, BrazilUniversidade Federal de São Paulo, Microbiol Immunol & Parasitol Dept, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem, São Paulo, BrazilFAPESP: 2011/12306-1FAPESP: 2010/18715-8CAPES: 2867/10Web of Scienc
Barriers to disseminating brief CBT for voices from a lived experience and clinician perspective
Access to psychological therapies continues to be poor for people experiencing psychosis. To address this problem, researchers are developing brief interventions that address the specific symptoms associated with psychosis, i.e., hearing voices. As part of the development work for a brief Cognitive Behaviour Therapy (CBT) intervention for voices we collected qualitative data from people who hear voices (study 1) and clinicians (study 2) on the potential barriers and facilitators to implementation and engagement. Thematic analysis of the responses from both groups revealed a number of anticipated barriers to implementation and engagement. Both groups believed the presenting problem (voices and psychosis symptoms) may impede engagement. Furthermore clinicians identified a lack of resources to be a barrier to implementation. The only facilitator to engagement was reported by people who hear voices who believed a compassionate, experienced and trustworthy therapist would promote engagement. The results are discussed in relation to how these barriers could be addressed in the context of a brief intervention using CBT techniques
Socio-demographic characteristics and psychosocial consequences of sickle cell disease: the case of patients in a public hospital in Ghana
The effect of emotional context on cognitive inhibition and attentional processing in dissociative identity disorder
In light of previous research, the current study tested the hypothesis that dissociative identity disorder (DID) would be characterised by effective cognitive inhibitory functioning when tested in a neutral context, but weakened inhibition when tested in an emotionally negative context. Using a negative priming task (i.e. the flanker task) to assess inhibitory ability 11 DID, 11 depressed, and 11 general population participants were tested in the two differing experimental contexts. The contexts were manipulated by instructions and word stimuli, and following the completion of this task participants completed the Dissociative Experiences Scale and the Schizotypal Personality Scale. DID participants displayed a greater degree of self-reported anxiety in the negative context and as expected displayed a reduction in inhibition in this context but not in the neutral context. The degree of negative priming for the depressed and general population samples remained stable across contexts as did their anxiety levels. The DID sample displayed slower response times to negative compared to neutral words but this attentional bias was not evident for the two comparison groups. The relationship between increased arousal, inhibitory functioning, dissociation and information processing in DID is discussed
Shame in dissociative disorders
This study examined shame and responses to it in adult dissociative disorder (DD; n = 24) and comparison psychiatric (n = 14) samples. To investigate how helpful different therapeutic responses are after shame disclosures in therapy, participants heard two vignettes from "mock" patients disclosing a) shame and b) surprise. Participants rated the helpfulness of five potential responses. Interventions covered withdrawing from the affect (withdrawal focused) to feeling it (feeling focused), with other interventions on cognitions (cognitive focused), management strategies (management focused), and previous experiences (history focused). The DD sample reported higher characterological and bodily shame, and more shame avoidance and withdrawal. There was no difference across groups for intervention ratings. For shame, interventions focused on feelings, cognitions, or previous shame experiences were deemed most helpful, but this was qualified by experiencing dissociation while hearing the script, where the history intervention was reported less helpful. Exposure to shame while monitoring dissociation should accompany therapy for DDs
Childhood Trauma and Active Mental Processes: Dissociation and Metacognition Influence Control of Negative Thoughts
Among trauma survivors, efforts to control distressing thoughts may be linked with dissociation. We examined the hypothesis that dissociation was related to metacognitive need to control thoughts (NCT); and explored dissociation and NCT as mediators between trauma and thought control techniques in a sample of college students. Dissociation was positively related to NCT and to childhood betrayal trauma (abuse by someone close to the victim). Dissociation and NCT mediated the relationship between childhood betrayal trauma and strategies used to control negative thoughts. Overall, childhood betrayal trauma was associated with NCT and with the use of active thought control methods such as reappraisal and worry, which require focusing directly on the thought; dissociation mediates this relationship. Therapeutic approaches that enhance awareness for cognitive and emotional experiences may be helpful for dissociative trauma survivors