αV Integrin Induces Multicellular Radioresistance in Human Nasopharyngeal Carcinoma via Activating SAPK/JNK Pathway

BACKGROUND:Tumor cells acquire the capacity of resistance to chemotherapy or radiotherapy via cell-matrix and cell-cell crosstalk. Integrins are the most important cell adhesion molecules, in which αV integrin mainly mediating the tight contact between tumor cells. METHODOLOGY/PRINCIPAL FINDINGS:To investigate the role of αV integrin in multi-cellular radioresistance (MCR) of human nasopharyngeal carcinoma (NPC), we performed immunohistochemistry and Western blotting to find that the expression of αV integrin in the tumor tissue of radioresistant patients is much higher than that in radiosensitive patients. In vitro, we cultured human NPC cell line CNE-2 cells as multi-cellular spheroids (MCSs) or as monolayer cells (MCs), and found that the expression of αV integrin in MCSs is significantly higher than that in MCs. MTT, flow cytometry and clonogenic survival assays showed that MCSs are less sensitive to X-ray irradiation than MCs while blocking of αV integrin in MCSs dramatically reversed their radioresistance. Furthermore, as detected by Western blotting, MCSs displayed sustained activation of the stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) pathway in presence of irradiation. Blocking of αV integrin in MCSs decreased the expression of phosphorylated JNK. Additionally, blocking of SAPK/JNK signaling pathway synergistically induced apoptosis of MCSs exposed to irradiation by increasing the expression of cleaved caspase-3. In vivo, we found that irradiation combined with αV integrin blocking treatment significantly enhanced the radiosensitivity of NPC xenografts. CONCLUSIONS:Our results indicate a novel role of αV integrin in multi-cellular radioresistance of NPCs

External validation suggests Integrin beta 3 as prognostic biomarker in serous ovarian adenocarcinomas

<p>Abstract</p> <p>Background</p> <p>The majority of women with ovarian cancer are diagnosed in late stages, and the mortality rate is high. The use of biomarkers as prognostic factors may improve the treatment and clinical outcome of these patients. We performed an external validation of the potential biomarkers CLU, ITGB3, CAPG, and PRAME to determine if the expression levels are relevant to use as prognostic factors.</p> <p>Methods</p> <p>We analysed the gene expression of CLU, ITGB3, CAPG, and PRAME in 30 advanced staged serous adenocarcinomas with quantitative real-time polymerase chain reaction (QPCR) and the protein levels were analysed in 98 serous adenocarcinomas with western blot for semiquantitative analysis. Statistical differences in mRNA and protein expressions between tumours from survivors and tumours from deceased patients were evaluated using the Mann-Whitney U test.</p> <p>Results</p> <p>The gene and protein ITGB3 (Integrin beta 3) were significantly more expressed in tumours from survivors compared to tumours from deceased patients, which is in concordance with our previous results. However, no significant differences were detected for the other three genes or proteins CLU, CAPG, and PRAME.</p> <p>Conclusion</p> <p>The loss of ITGB3 expression in tumours from deceased patients and high expression in tumours from survivors could be used as a biomarker for patients with advanced serous tumours.</p

Is there any relationship between children psychopathology and interactive family pattern?

Introduction The study “LTP used as a psychodiagnostic and therapeutic tool for psychiatric children and adolescents” is part of a Neuropsychiatric Unit project (NPU), aiming to find out significant relationships between children psychopathology and interactive families pattern in order to set up a functional therapeutic intervention. Method The target group evaluated by the NPIA was composed of 20 families with school-age children. During the evaluation psychodiagnostic assessment the Child Behavior Checklist (CBCL, Achenbach 2000-2001) and the LTP (Fivaz-Depeursinge and Corboz-Warnery, 1999) were administered. In order to test the hypothesis we have made the following statistical analysis: a) LTP score flow (during the different phases) comparison between the clinical-borderline and non-clinical CBCL groups (generalized linear model). b) parental LTP variable scores (in each phases) comparison between clinical-borderline and non-clinical CBCL groups (t-test for independent groups). c) correlations between LTP and CBCL scores. Results Statistical differences both in LTP scores flow and in LTP variables scores in each part between clinical-borderline and non- clinical CBCL groups only in some specific psychopathological areas (attention, social and total problems, externalizing, anxious- depressed, withdrawn-depressed and somatic complaints). It is interesting that these differences are due to some of the LTP variables concerning parental abilities (co-construction, scaffolding, conflict and interferences, affective warmth, validation, activities errors). Finally better parental abilities in LTP affective warmth and validation, activities errors, parental support, scaffolding and co-construction are related to elevated scores in somatic complaints, total and social problems or viceversa (positive correlations). Conclusions These results indicated a relationship between psychopathological children symptoms and parental abilities to manage triadic interactions supporting recent developmental theories which stressed the importance to involve the global family system in diagnostic assessment in order to propose an intervention that could best fit to the patient family context

Intergenerational transmission of attachment. Family interactive dynamics and psychopathology: what kind of relation in adolescence?

Introduction: this work is an example of empirical research. Its aim is to look to the possible intergenerational influence between parents and adolescents attachment bond to their respective parents, infant armonic and/or disarmonic development and functional or dysfunctional family interactions (Main, Kaplan e Cassidy, 1985). Method: 40 families with adolescents aged from 12 to 18 (\u3bc = 14.575, \u3c3 = 1.716) coming for a psychodiagnostic evaluation were tested with Lausanne Trilogue Play (LTP, Fivaz-Depeursinge & Corboz-Warnery, 1999), Parental Bonding Instrument (PBI, Parker, Tupling & Brown, 1979), Child Behaviour Check-List (CBCL, parents form) and Youth Self Report (YSR, adolescents form) (Achenbach, 2000-2001). Hypothesis: a) is there an association between the adolescent\u2018s perceived attachment relationship with his parents and his psychopathological symptoms? b) is there an association between parents-adolescent interactive dynamics and the parents\u2018 perceveid attachment relationship with their parents (adolescent\u2018s grand-parents). Results: a) ANOVA: significative statistical differences (p < .05) between adolescent psychopathology and the quality of perceived relationship with both the mother (affect without control) and the father (controlled affect). b) non-parametric Kruskal Wallis test for k indipendent groups: significant statistical differences (\u3b1 < 0.05) between quality of relationship between the mother and her mother (adolescent\u2018s grand-mother) and some interactive dynamics: inclusion, co-construction, scaffolding, affect validation, total score of the part where the mother has an active role. No significant statistical differences for the father. Discussion: these results underline a significant association between the internal working model of the mother and her ways to interact and manage the relation with her adolescent son; this is a clinical evidence too. Another relevant result is the association between adolescent\u2018s psychopathology and his internal working model

INTERVENTO PSICOMOTORIO CON IL BAMBINO PREMATURO

The present work aims to highlight the usefulness of instruments such as the Lausanne Triadic Play (LTP) and the Temperament Questionnaire Italian (QUIT) in the detection of elements that consider the child in relation to family, his primary environment. These elements, which is not apparent just from observation of child development, which remains the main tool of the therapist, are an added value for the operation and monitoring carried out by the team rehabilitation. In addition, the direct involvement of the family in the rehabilitation project is a way to further enhance the therapeutic alliance. The study showed a significant correlation between the surveys carried out by the use of three instruments. the observation of the child in his interactions with parents can be extremely helpful for the therapist, in order to prevent distortion of any interactive dynamics present within the family, in collaboration with the multidisciplinary rehabilitation team and to design therapeutic intervention involving not only the child but also the family in an active way. This work explores how the relational variables and temperamental affect rehabilitative intervention and, conversely, how the rehabilitative intervention affects the temperament and family relationships

Alexithymia and behavioral disorders as risk factors for alcohol misuse in adolescence.

Introduction Alcohol is the psychoactive substance most used by adolescents, lately their alcohol abuse has become internationally a serious public health concern. Psychobehavioral factors research relating to alcohol abuse has led to various studies identifying several psychopathological disorders and alexithymic traits in adults.This relationship has to be analyzed in adolescents however. Method The present study aimed to assess alcohol consumption and its possible relationship with psychological vulnerability, in terms of psychobehavioral problems and alexithymia. The study was conducted on a sample of 1466 pupils attending secondary school (grades 6 to 13), consisting of 53,6% males and 46,4 % females, with a mean age of 13,5 years ± 1,7 SD. These adolescents were administered the Adolescents’ Saturday Nights Questionnaire to quantify their alcohol consumption, the Toronto Alexithymic Scale for developmental age to identify any alexithymic traits, the Strengths and Difficulties Questionnaire, and the Youth Self-Report 11-18 to detect any psychobehavioral problems. Results Males drank more alcohol than females, and their consumption increased with age. Alexithymia was more widespread and stable among females, and tended to increase from 11 to 13 years old, then decreased gradually from 14 to 17 years old. An association between alcohol consumption and psychobehavioral problems was identified in the whole sample, while a statistically significant correlation between alcohol consumption and alexithymia only emerged in the subsample of 6th- to 8th-graders. Among this younger group, those returning the highest scores for alexithymia and psychobehavioral problems also reported significantly higher alcohol consumption than their peers without such psychological issues. Conclusions Alexithymic traits are a risk factor for alcohol consumption in preadolescence, especially when associated with psychobehavioral problems. Preventive measures designed for such young adolescents should therefore concentrate on improving their emotional awarenes

1-42 B-amyloid peptide (AB1-42) requires PDK1/nPKCs/Rac 1 pathway to induce neuronal death

1–42 β-Amyloid (Aβ1–42) peptide is a key molecule involved in the development of Alzheimer's disease. Some of its effects are manifested at the neuronal morphological level. These morphological changes involve loss of neurites due to cytoskeleton alterations. However, the mechanism of Aβ1–42 peptide activation of the neurodegenerative program is still poorly understood. Here, Aβ1–42 peptide-induced transduction of cellular death signals through the phosphatidylinositol 3-kinase (PI3K)/phosphoinositol-dependent kinase (PDK)/novel protein kinase C (nPKC)/Rac 1 axis is described. Furthermore, pharmacological inhibition of PDK1 and nPKC activities blocks Rac 1 activation and neuronal cell death. Our results provide insights into an unsuspected connection between PDK1, nPKCs and Rac 1 in the same signal-transduction pathway and points out nPKCs and Rac 1 as potential therapeutic targets to block the toxic effects of Aβ1–42 peptide in neurons.Fil: Manterola, L.. Biodonostia Institute, Hospital Donostia; EspañaFil: Hernando Rodriguez, M.. National Cancer Research Center; EspañaFil: Ruiz, A.. Universidad del Pais Vasco; España. Achucarro Basque Center for Neuroscience; EspañaFil: Apraiz, A.. Universidad del Pais Vasco; EspañaFil: Arrizabalaga, O.. Universidad del Pais Vasco; EspañaFil: Vellon, L.. Fundación Instituto de Investigación Biomédica y Desarrollo Tecnológico (INBIOMED); EspañaFil: Alberdi, E.. Universidad del Pais Vasco; EspañaFil: Cavaliere, F.. Universidad del Pais Vasco; EspañaFil: Lacerda, H.M.. Università degli Studi di Torino; ItaliaFil: Jimenez, S.. Universidad de Sevilla; España. Consejo Superior de Investigaciones Cientificas; EspañaFil: Parada, Luis Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; Argentina. Universidad Nacional de Salta; ArgentinaFil: Matute, C.. Universidad del Pais Vasco; EspañaFil: Zugaza, Jose Luis. Universidad del Pais Vasco; España. Bizkaia Science and Technology Park; Españ