TP53-induced glycolysis and apoptosis regulator promotes proliferation and invasiveness of nasopharyngeal carcinoma cells

The TP53induced glycolysis and apoptosis regulator (TIGAR) is the protein product of the p53 target gene, C12orf5. TIGAR blocks glycolysis and promotes cellular metabolism via the pentose phosphate pathway; it promotes the production of cellular nicotinamide adenine dinucleotide phosphate (NADPH), which leads to enhanced scavenging of intracellular reactive oxygen species, and inhibition of oxidative stressinduced apoptosis in normal cells. Our previous study identified a novel nucleoside analog that inhibited cellular growth and induced apoptosis in nasopharyngeal carcinoma (NPC) cell lines via downregulation of TIGAR expression. Furthermore, the growth inhibitory effects of cMet tyrosine kinase inhibitors were ameliorated by the overexpression of TIGAR in the NPC cell lines. These results indicate a significant role for TIGAR expression in the survival of NPCs. The present study aimed to further define the function of TIGAR expression in NPC cells. In total, 36 formalinfixed, paraffinembedded NPC tissue samples were obtained for the immunohistochemical determination of TIGAR expression. The effects of TIGAR expression on cell proliferation, NADPH production and cellular invasiveness were also assessed in NPC cell lines. Overall, TIGAR was overexpressed in 27/36 (75%) of the NPC tissues compared with the adjacent noncancer epithelial cells. Similarly, TIGAR overexpression was also observed in a panel of six NPC cell lines compared with normal NP460 hTert and Het1A cell lines. TIGAR overexpression led to increased cellular growth, NADPH production and invasiveness of the NPC cell lines, whereas a knockdown of TIGAR expression resulted in significant inhibition of cellular growth and invasiveness. The expression of the two mesenchymal markers, fibronectin and vimentin, was increased by TIGAR overexpression, but reduced following TIGARknockdown. The present study revealed that TIGAR overexpression led to increased cellular growth, NADPH production and invasiveness, and the maintenance of a mesenchymal phenotype, in NPC tissues.published_or_final_versio

Sexualidade da pessoa com deficiência intelectual - Atitudes de pais e profissionais

Dissertação de Mestrado em Psicologia Educacional, apresentada ao ISPA - Instituto UniversitárioTendo em conta que as atitudes dos pais e profissionais face à sexualidade das pessoas com deficiência intelectual têm um papel preponderante na disponibilização de oportunidades de vivências e experiências sexuais e na passagem de informação correcta acerca da sexualidade (Brown & Pirtle, 2008), o presente estudo pretende conhecer e analisar as atitudes e necessidades que ambos têm, bem como verificar se existem diferenças estatisticamente significativas entre elas. Tendo sido utilizada uma abordagem mista através da utilização do questionário ASQ-ID- Attitudes to Sexuality Questionnaire (Individuals with an Intellectual Disability) e de uma entrevista semi-estruturada, o presente estudo contou com uma amostra de 130 participantes (80 profissionais e 50 pais), dos quais três mães e três profissionais foram entrevistados. Os resultados obtidos confirmaram a nossa hipótese de que existem diferenças estatisticamente significativas nas atitudes dos pais e profissionais, demonstrando que os profissionais têm atitudes mais liberais. Através das entrevistas, verificámos que os profissionais têm necessidades de formação no que toca à capacidade para intervirem de forma adequada nas várias manifestações sexuais dos seus clientes, tendo sido enfatizada a necessidade do envolvimento da família neste processo, a consideração das diferenças individuais e a promoção de contextos favoráveis nas instituições para as vivências e experiências sexuais desta população. Por fim, atestou-se ainda através do discurso dos inquiridos, a falta de um consenso dentro das instituições acerca daquilo que devem fazer em situações onde os clientes necessitam de resposta.ABSTRACT: Given that the attitudes of parents and professionals towards sexuality of people with intellectual disabilities have a role in providing opportunities for experiences and sexual experiences and pass correct information about sexuality (Brown & Pirtle, 2008), this study seeks to examine and analyze the attitudes and needs that both have and see if there are statistically significant differences between them. Having used a mixed approach by using the questionnaire ASQ-ID-Attitudes to Sexuality Questionnaire (Individuals with an Intellectual Disability) and a semi-structured interview, this study involved a sample of 130 participants (80 professionals and 50 parents), of which three mothers and three professionals were interviewed. The results confirmed our hypothesis that there are significant differences in the attitudes of parents and professionals, demonstrating that professionals have more liberal attitudes. Through the interviews, we found that professionals have training needs in relation to the ability to intervene appropriately in various sexual manifestations of its customers, having emphasized the need to involve the family in this process, consideration of individual differences and promoting favorable contexts in institutions for sexual experiences and the experiences of this population. Finally, it is also attested by the discourse of the respondents, the lack of consensus within institutions about what they should do in situations where customers need to be answered

Clinical significance of frizzled homolog 3 protein in colorectal cancer patients

2013-2014 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Transport of Folded Proteins by the Tat System

The twin-arginine protein translocation (Tat) system has been characterized in bacteria, archaea and the chloroplast thylakoidal membrane. This system is distinct from other protein transport systems with respect to two key features. Firstly, it accepts cargo proteins with an N-terminal signal peptide that carries the canonical twin-arginine motif, which is essential for transport. Second, the Tat system only accepts and translocates fully folded cargo proteins across the respective membrane. Here, we review the core essential features of folded protein transport via the bacterial Tat system, using the three-component TatABC system of Escherichia coli and the two-component TatAC systems of Bacillus subtilis as the main examples. In particular, we address features of twin-arginine signal peptides, the essential Tat components and how they assemble into different complexes, mechanistic features and energetics of Tat-dependent protein translocation, cytoplasmic chaperoning of Tat cargo proteins, and the remarkable proofreading capabilities of the Tat system. In doing so, we present the current state of our understanding of Tat-dependent protein translocation across biological membranes, which may serve as a lead for future investigations

Proceedings of the Annual Hawaii International Conference on System Sciences

The significant human impact on the environment has prompted many governments to invest in sustainability initiatives across cities and communities. Moreover, although it has been suggested that information technology can aid in the development of these sustainability initiatives, there is a dearth of empirical field studies in this area. In this research-in-progress paper, we present preliminary findings from a case study of a private-public partnership (PPP) community-based sustainability initiative that is enabled by a digital platform. Preliminary analysis sheds light on the mechanisms underlying the formation of the PPP, the development of the PPP's business model, the development of the digital platform, and ultimately the emergence of a community for sustainability. a framework for digital platform-enabled community development is posited based on the case analysis. Implications to both research and practice, as well as future research work are then discussed in concluding this paper

Proteomic comparison of nasopharyngeal cancer cell lines C666-1 and NP69 identifies down-regulation of annexin II and β 2-tubulin for nasopharyngeal carcinoma

Context. - Nasopharyngeal carcinoma (NPC), common in southern China and North Africa, has a complex etiology involving interplay between viral, environmental, and hereditary factors and is almost constantly associated with the Epstein-Barr virus. Since the prognosis of locally advanced and metastatic diseases is poor, increased understanding of the pathogenesis of NPC would be important for discovering novel markers for patients' management. Objectives. - To compare the proteomic expression profile between an Epstein-Barr virus-associated NPC cell line (C666-1) and a normal NP cell line (NP69). The proteins with differential expression were analyzed in 40 undifferentiated NPC paraffin-embedded specimens. Design. - Differentially expressed proteins discovered between the two cell lines were identified by mass spectrometry. After confirmation by immunocytochemical staining, their expression in patient samples was measured using 40 pairs of undifferentiated NPCs together with their adjacent normal epithelia. Results. - Proteomic findings indicated that adenosine triphosphate synthase α chain was up-regulated, whereas annexin II, annexin V, β 2-tubulin, and profilin 1 were down-regulated. After confirming the results in agar-processed cell lines, annexin II and β 2-tubulin expression were found to be lower in tumor cells than in adjacent normal epithelial cells in 100% and 90% of the patients' specimens, respectively. Finally, annexin II down-regulation was positively associated with lymph node metastasis, suggesting that it may be a prognostic factor in NPC. Conclusions. - The results suggest that annexin II and β 2- tubulin down-regulation is important in NPC formation and may represent potential targets for further investigations.link_to_subscribed_fulltex

Comparison of protein expression patterns between hepatocellular carcinoma cell lines and a hepatoblastoma cell line

Hepatocellular carcinoma (HCC) and hepatoblastoma (HB) are malignancies of the liver with different etiologies, but the HB cell line HepG2 has been frequently used in various studies of HCC. In this study, we compare the protein expression patterns between HepG2 cells and three HCC cell lines, HKCI-2, HKCI-3, and HKCI-4, respectively. The cell lysates of individual cell lines were separated by two-dimensional polyacrylamide gel electrophoresis. The protein spots in the gel images were quantified and compared by image analysis software. The differentially expressing proteins were then identified by tryptic peptide mass fingerprinting. Compared with the HepG2 cells, the normalized quantities of 49 and 58 protein spots were found to be at least twofold higher and twofold lower, respectively, in all three HCC cell lines. The differentially expressed proteins can be grouped into structural proteins (annexins, transgelin, laminin receptor), stress-induced proteins (HSP27, 60, and 70), enzymes (aldehyde dehydrogenase, pyruvate kinase, α-enolase, etc.), and transcription factors (far upstream element binding protein 2, GTP-binding nuclear protein RAN). Some of these proteins play important roles in regulating homeostasis, drug resistance, apoptosis, cell differentiation, cell growth, and metastasis. In conclusion, our proteomic data indicate that there are considerable differences in the protein expression patterns between HepG2 cells and the HCC cells, suggesting differences m cellular properties. Hence, HepG2 may not be a good cell line model for studying HCC. Copyright © Humana Press Inc. All rights of any nature whatsoever are reserved.link_to_subscribed_fulltex

Enhancing anti-tumour innate immunity by targeting the DNA damage response and pattern recognition receptors in combination with radiotherapy

Radiotherapy is one of the most effective and frequently used treatments for a wide range of cancers. In addition to its direct anti-cancer cytotoxic effects, ionising radiation can augment the anti-tumour immune response by triggering pro-inflammatory signals, DNA damage-induced immunogenic cell death and innate immune activation. Anti-tumour innate immunity can result from recruitment and stimulation of dendritic cells (DCs) which leads to tumour-specific adaptive T-cell priming and immunostimulatory cell infiltration. Conversely, radiotherapy can also induce immunosuppressive and anti-inflammatory mediators that can confer radioresistance. Targeting the DNA damage response (DDR) concomitantly with radiotherapy is an attractive strategy for overcoming radioresistance, both by enhancing the radiosensitivity of tumour relative to normal tissues, and tipping the scales in favour of an immunostimulatory tumour microenvironment. This two-pronged approach exploits genomic instability to circumvent immune evasion, targeting both hallmarks of cancer. In this review, we describe targetable DDR proteins (PARP (poly[ADP-ribose] polymerase); ATM/ATR (ataxia–telangiectasia mutated and Rad3-related), DNA-PKcs (DNA-dependent protein kinase, catalytic subunit) and Wee1 (Wee1-like protein kinase) and their potential intersections with druggable immunomodulatory signalling pathways, including nucleic acid-sensing mechanisms (Toll-like receptors (TLR); cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) and retinoic acid-inducible gene-I (RIG-I)-like receptors), and how these might be exploited to enhance radiation therapy. We summarise current preclinical advances, recent and ongoing clinical trials and the challenges of therapeutic combinations with existing treatments such as immune checkpoint inhibitors.</jats:p