MORTALIDADE POR CÂNCER NO ESTADO DE MATO GROSSO DO SUL, BRASIL, NO PERÍODO DE 1998 A 2007

Atualmente, as ferramentas de Sensoriamento Remoto e Geoprocessamento vêm sendo cada vez mais utilizadas em estudos ambientais, socioeconômicos e de eventos relacionados à saúde de forma geral. Desta forma, o objetivo deste trabalho foi analisar a variação geográfica e as tendências temporais da mortalidade por neoplasias malignas no Estado de Mato Grosso do Sul, no período de 1998 a 2007, com o auxílio do geoprocessamento. Os dados de mortalidade foram obtidos a partir do Sistema de Informação de Mortalidade (SIM), disponíveis na Internet. Como produtos sínteses foram gerados mapas temáticos. Na análise de causas de óbitos no período de 1998 a 2007, observou-se que as neoplasias ocupavam o 3º lugar como causas de mortes, correspondendo a 13,78 % das mesmas No referido período, a neoplasia maligna da traquéia, brônquios e pulmões foi a que mais causou óbitos (12%), seguido do câncer de estômago (8,87%). Os cânceres próprios de cada gênero também estão presentes com alta mortalidade, como o câncer de próstata (14,48%) e da traquéia, brônquios e pulmões (14,06%) no sexo masculino e os de mama (13,76%) e colo uterino (7,45%) no sexo feminino. As 10 topografias de maior mortalidade correspondem a 64 % de todas as mortes por câncer.

MORTALIDADE POR CÂNCER NO ESTADO DE MATO GROSSO DO SUL, BRASIL, NO PERÍODO DE 1998 A 2007

Atualmente, as ferramentas de Sensoriamento Remoto e Geoprocessamento vêm sendo cada vez mais utilizadas em estudos ambientais, socioeconômicos e de eventos relacionados à saúde de forma geral. Desta forma, o objetivo deste trabalho foi analisar a variação geográfica e as tendências temporais da mortalidade por neoplasias malignas no Estado de Mato Grosso do Sul, no período de 1998 a 2007, com o auxílio do geoprocessamento. Os dados de mortalidade foram obtidos a partir do Sistema de Informação de Mortalidade (SIM), disponíveis na Internet. Como produtos sínteses foram gerados mapas temáticos. Na análise de causas de óbitos no período de 1998 a 2007, observou-se que as neoplasias ocupavam o 3º lugar como causas de mortes, correspondendo a 13,78 % das mesmas No referido período, a neoplasia maligna da traquéia, brônquios e pulmões foi a que mais causou óbitos (12%), seguido do câncer de estômago (8,87%). Os cânceres próprios de cada gênero também estão presentes com alta mortalidade, como o câncer de próstata (14,48%) e da traquéia, brônquios e pulmões (14,06%) no sexo masculino e os de mama (13,76%) e colo uterino (7,45%) no sexo feminino. As 10 topografias de maior mortalidade correspondem a 64 % de todas as mortes por câncer. Arcgis � o0�X߬ue apresentavam o mesmo conteúdo, com formas de representação diferenciadas, visando avaliar a sua comunicação cartográfica. São apresentados os resultados de análises realizadas por 20 indivíduos selecionados (alunos, professores e não estudantes) que indicaram quais mapas eram mais legíveis em termos de clareza, simplicidade e objetidade de conteúdo. 

Levels of awareness of professional ethics used as a sensitizing method in project-based learning

There is a need for educational frameworks for computer ethics education. This discussion paper presents an approach to developing students’ moral sensitivity, an awareness of morally relevant issues, in project-based learning (PjBL). The proposed approach is based on a study of IT professionals’ levels of awareness of ethics. These levels are labelled My world, The corporate world, A shared world, The client’s world and The wider world. We give recommendations for how instructors may stimulate students’ thinking with the levels and how the levels may be taken into account in managing a project course and in an IS department. Limitations of the recommendations are assessed and issues for discussion are raised.

High frequency of BRAF mutations in nevi

To evaluate the timing of mutations in BRAF (v-raf murine sarcoma viral oncogene homolog B1) during melanocytic neoplasia, we carried out mutation analysis on microdissected melanoma and nevi samples. We observed mutations resulting in the V599E amino-acid substitution in 41 of 60 (68%) melanoma metastases, 4 of 5 (80%) primary melanomas and, unexpectedly, in 63 of 77 (82%) nevi. These data suggest that mutational activation of the RAS/RAF/MAPK pathway in nevi is a critical step in the initiation of melanocytic neoplasia but alone is insufficient for melanoma tumorigenesis.

Australian laws and policies on child neglect

This chapter describes the features of different Australian State and Territory laws and policies about child neglect. It makes observations about three major domains of law and policy: laws about child neglect to enable protection of children who are suffering severe neglect (child protection laws); laws and policies about the provision of services for children and their families when experiencing neglect (support-oriented laws and policies); and criminal laws about child neglect.

Strategies for the prevention of cervical cancer by human papillomavirus vaccination

As cervical cancer is causally associated with 14 high-risk types of human papillomavirus (HPV), a successful HPV vaccine will have a major impact on this disease. Although some persistent HPV infections progress to cervical cancer, host immunity is generally able to clear most HPV infections. Both cell-mediated and antibody responses have been implicated in influencing the susceptibility, persistence or clearance of genital HPV infection. There have been two clinical trials that show that vaccines based on virus-like particles (VLPs) made from the major capsid protein, L1, are able to type specifically protect against cervical intra-epithelial neoplasia and infection. However, there is no evidence that even a mixed VLP vaccine will protect against types not included in the vaccine, and a major challenge that remains is how to engineer protection across a broader spectrum of viruses. Strategies for production of HPV vaccines using different vaccine vectors and different production systems are also reviewed. © 2005 Elsevier Ltd. All rights reserved.

More men than women make mucosal IgA antibodies to human papillomavirus type 16 (HPV-16) and HPV-18: A study of oral HPV and oral HPV antibodies in a normal healthy population

Background: We have previously shown the high prevalence of oral anti-human papillomavirus type 16 (HPV-16) antibodies in women with HPV-associated cervical neoplasia. It was postulated that the HPV antibodies were initiated after HPV antigenic stimulation at the cervix via the common mucosal immune system. The present study aimed to further evaluate the effectiveness of oral fluid testing for detecting the mucosal humoral response to HPV infection and to advance our limited understanding of the immune response to HPV. Methods: The prevalence of oral HPV infection and oral antibodies to HPV types 16, 18 and 11 was determined in a normal, healthy population of children, adolescents and adults, both male and female, attending a dental clinic. HPV types in buccal cells were determined by DNA sequencing. Oral fluid was collected from the gingival crevice of the mouth by the OraSure method. HPV-16, HPV-18 and HPV-11 antibodies in oral fluid were detected by virus-like particle-based enzyme-linked immunosorbent assay. As a reference group 44 women with cervical neoplasia were included in the study. Results: Oral HPV infection was h ighest in children (9/114, 7.9%), followed by adolescents (4/78, 5.1%), and lowest in normal adults (4/116, 3.5%). The predominant HPV type found was HPV-13 (7/22, 31.8%) followed by HPV-32 (5/22, 22.7%). The prevalence of oral antibodies to HPV-16, HPV-18 and HPV-11 was low in children and increased substantially in adolescents and normal adults. Oral HPV-16 IgA was significantly more prevalent in women with cervical neoplasia (30/44, 68.2%) than the women from the dental clinic (18/69, 26.1% P = 0.0001). Significantly more adult men than women displayed oral HPV-16 IgA (30/47 compared with 18/69, OR 5.0, 95% CI 2.09-12.1, P < 0.001) and HPV-18 IgA (17/47 compared with 13/69, OR 2.4, 95% CI 0.97-6.2, P = 0.04). Conclusion: The increased prevalence of oral HPV antibodies in adolescent individuals compared with children was attributed to the onset of sexual activity. The increased prevalence of oral anti-HPV IgA in men compared with women was noteworthy considering reportedly fewer men than women make serum antibodies, and warrants further investigation. © 2006 Marais et al; licensee BioMed Central Ltd.

The N550K/H mutations in FGFR2 confer differential resistance to PD173074, dovitinib and ponatinib ATP-competitive inhibitors

We sought to identify fibroblast growth factor receptor 2 (FGFR2) kinase domain mutations that confer resistance to the pan-FGFR inhibitor, dovitinib, and explore the mechanism of action of the drug-resistant mutations. We cultured BaF3 cells overexpressing FGFR2 in high concentrations of dovitinib and identified fourteen dovitinib-resistant mutations, including the N550K mutation observed in 25% of FGFR2mutant endometrial cancers (EC). Structural and biochemical in vitro kinase analyses, together with BaF3 proliferation assays, showed that the resistance mutations elevate the intrinsic kinase activity of FGFR2. BaF3 lines were used to assess the ability of each mutation to confer cross-resistance to PD173074 and ponatinib. Unlike PD173074, ponatinib effectively inhibited all the dovitinib-resistant FGFR2 mutants except the V565I gatekeeper mutation, suggesting ponatinib but not dovitinib targets the active conformation of FGFR2 kinase. EC cell lines expressing wild-type FGFR2 were relatively resistant to all inhibitors. Whereas EC cell lines expressing mutated FGFR2 showed differential sensitivity. Within the FGFR2mutant cell lines, 3/7 showed marked resistance to PD173074 and relative resistance to dovitinib and ponatinib. This suggests that alternative mechanisms distinct from kinase domain mutations are responsible for intrinsic resistance in these three EC lines. Finally, overexpression of FGFR2N550K in JHUEM-2 cells (FGFR2C383R) conferred resistance (~5 fold) to PD173074, providing independent data that FGFR2N550K can be associated with drug resistance. Biochemical in vitro kinase analyses also shows ponatinib is more effective than dovitinib at inhibiting FGFR2N550K. We propose tumors harboring mutationally activated FGFRs should be treated with FGFR inhibitors that specifically bind the active kinase.

Loss of chromosomal integrity in human mammary epithelial cells subsequent to escape from senescence

The genomic changes that foster cancer can be either genetic or epigenetic in nature. Early studies focused on genetic changes and how mutational events contribute to changes in gene expression. These point mutations, deletions and amplifications are known to activate oncogenes and inactivate tumor suppressor genes. More recently, multiple epigenetic changes that can have a profound effect on carcinogenesis have been identified. These epigenetic events, such as the methylation of promoter sequences in genes, are under active investigation. In this review we will describe a methylation event that occurs during the propagation of human mammary epithelial cells (HMEC) in culture and detail the accompanying genetic alterations that have been observed.

The epithelial-mesenchymal transition : new insights in signaling, development, and disease

The conversion of an epithelial cell to a mesenchymal cell is critical to metazoan embryogenesis and a de. ning structural feature of organ development. Current interest in this process, which is described as an epithelial- mesenchymal transition (EMT), stems from its developmental importance and its involvement in several adult pathologies. Interest and research in EMT are currently at a high level, as seen by the attendance at the recent EMT meeting in Vancouver, Canada (October 1-3, 2005). The meeting, which was hosted by The EMT International Association, was the second international EMT meeting, the . rst being held in Port Douglas, Queensland, Australia in October 2003. The EMT International Association was formed in 2002 to provide an international body for those interested in EMT and the reverse process, mesenchymal-epithelial transition, and, most importantly, to bring together those working on EMT in development, cancer, . brosis, and pathology. These themes continued during the recent meeting in Vancouver. Discussion at the Vancouver meeting spanned several areas of research, including signaling pathway activation of EMT and the transcription factors and gene targets involved. Also covered in detail was the basic cell biology of EMT and its role in cancer and . brosis, as well as the identi. cation of new markers to facilitate the observation of EMT in vivo. This is particularly important because the potential contribution of EMT during neoplasia is the subject of vigorous scientific debate (Tarin, D., E.W. Thompson, and D.F. Newgreen. 2005. Cancer Res. 65:5996-6000; Thompson, E.W., D.F. Newgreen, and D. Tarin. 2005. Cancer Res. 65:5991-5995).

Epithelial mesenchymal transition traits in human breast cancer cell lines parallel the CD44HI/CD24lO/-stem cell phenotype in human breast cancer

We review here the recently emerging relationship between epithelial-mesenchymal transition (EMT) and breast cancer stem cells (BCSC), and provide analyses of published data on human breast cancer cell lines, supporting their utility as a model for the EMT/BCSC state. Genome-wide transcriptional profiling of these cell lines has confirmed the existence of a subgroup with mesenchymal tendencies and enhanced invasive properties ('Basal B'/Mesenchymal), distinct from subgroups with either predominantly luminal ('Luminal') or mixed basal/luminal ('Basal A') features (Neve et al. Cancer Cell, 2006). A literature-derived EMT gene signature has shown specific enrichment within the Basal B subgroup of cell lines, consistent with their over-expression of various EMT transcriptional drivers. Basal B cell lines are found to resemble BCSC, being CD44highCD24low. Moreover, gene products that distinguish Basal B from Basal A and Luminal cell lines (Basal B Discriminators) showed close concordance with those that define BCSC isolated from clinical material, as reported by Shipitsin et al. (Cancer Cell, 2007). CD24 mRNA levels varied across Basal B cell lines, correlating with other Basal B Discriminators. Many gene products correlating with CD24 status in Basal B cell lines were also differentially expressed in isolated BCSC. These findings confirm and extend the importance of the cellular product of the EMT with Basal B cell lines, and illustrate the value of analysing these cell lines for new leads that may improve breast cancer outcomes. Gene products specific to Basal B cell lines may serve as tools for the detection, quantification, and analysis of BCSC/EMT attributes.

Epithelial-to-mesenchymal transitions and circulating tumor cells

Epithelial-to-mesenchymal transition (EMT) phenomena endow epithelial cells with enhanced migratory and invasive potential, and as such, have been implicated in many physiological and pathological processes requiring cell migration/invasion. Although their involvement in the metastatic cascade is still a subject of debate, data are accumulating to demonstrate the existence of EMT phenotypes in primary human tumors, describe enhanced metastatic potential of EMT derivatives in animal models, and report EMT attributes in circulating tumor cells (CTCs). The relationships between EMT and CTCs remain largely unexplored, and we review here in vitro and in vivo data supporting a putative role of EMT processes in CTC generation and survival.