Base teórica: Nas últimas décadas, o prognóstico do câncer inicial da mama tem sido baseado nas características clínicas das pacientes e em aspectos histológicos dos tumores. Nos últimos anos, subtipos moleculares de carcinoma de mama foram identificados através de estudos de perfil genético por “DNA microarray”. Esta nova classificação pode melhorar a avaliação prognóstica, porém ainda não está disponível e é de alto custo. A possibilidade de identificar subtipos moleculares através de métodos mais simples e de menor custo é particularmente importante em países com recursos limitados. A identificação de subtipos do câncer de mama é particularmente importante pelas implicações clínicas e pelas opções de tratamento. Métodos: Uma coorte retrospectiva de 71 pacientes consecutivas com carcinoma primário de mama de estágio clínico I e II, tratadas no Serviço de Mastologia do HCPA entre os anos de 1993 e 1997 com um seguimento mínimo de 5 anos.Foram revisados dados sobre características clínicas, histopatológicas, evolução clínica e desfechos apresentados no período. Foi realizada uma análise imunoistoquímica de blocos representativos dos tumores, avaliando-se o Receptor Estrogênico (RE), o Receptor de Progesterona (RP), o HER2, o Ki-67, o Bcl-2, o p53, o p63 e o CK8. Os objetivos foram determinar a prevalência do perfil molecular nesta população e em seus desfechos clínicos. Resultados: 39 tumores (54,9 %) foram luminal A; 15 tumores (21,1%) foram luminal B; 15 tumores (21,1) foram basais ou triplo negativos e somente 2 tumores (2,8%) foram HER2. Não houve diferença no prognóstico entre os subtipos de câncer de mama: luminal A (RH positivo e HER2 negativo); luminal B (RH positivo e HER2 positivo); HER2 (HER2 positivo) e basal (RH negativo, HER2 negativo) em relação à sobrevida livre de doença e à sobrevida global, embora apresentassem uma forte correlação com a diferenciação e com o grau tumoral. Provavelmente, isto se deve ao pequeno número de pacientes e ao prognóstico de pacientes com estágios iniciais da doença. Conclusões: Nossos resultados sugerem que é possível identificar os subtipos do câncer de mama pela análise imunoistoquímica de RE, RP e HER2, e que a adição de outros marcadores não melhora a estimativa de prognóstico. O perfil molecular pode ser um instrumento valioso para o manejo do câncer de mama em países com recursos limitados. / Background: In the last decades, prognostic evaluation of initial breast cancer is mostly based on patients’ clinical and tumoral histological features. Recently, molecular subtypes of invasive breast cancer were recognized through DNA microarray profiling studies. This new classification can potentially improve the prognostic evaluation but this technology is still not widely available and it’s too expensive. The possibility of identifying the molecular subtypes through simpler and cheaper methods is promising especially in countries with limited resorts. The identification of breast cancer subtypes is particularly important because it has clinical implications and for treatment options. Methods: A retrospective cohort of 71 consecutive patients with pathologic stage I or II primary breast carcinomas, treated in the HCPA Breast Unit, between 1993 and 1997 with a minimum follow up of 5 years , was studied. Histological and clinical features as well as clinical outcome and survival were reviewed. Immunohistochemical analysis was carried out in representative blocks of tumors with antibodies against Estrogen Receptor (ER),Progesterone Receptor (PR), Human Epidermal Growth Receptor – type 2 (HER2), Ki-67, Bcl-2, p53, p63 and CK8. The endpoints were to determine the prevalence the molecular portrait in this population and its clinical outcomes. Results: 39 tumors (54,9 %) were Luminal A, 15 tumors (21,1%) were Luminal B, 15 tumors (21,1) were Basal or triple negative and only 2 tumors (2,8%) were HER2. There was no prognostic difference among the breast cancer subtypes: luminal A (HR-positive and HER2 negative); luminal B (HR positive and HER2 positive); HER2 overexpressing (HER2 positive) and basal (HR negative, HER2 negative) relating to disease-free and overall survival, although there was a robust correlation with tumor grade and differentiation. This is probably related to limited number of patients in this study and prognosis of initial-stage patients. Conclusions: Our results suggest that it is possible to identify breast cancer subtypes by immunohistochemical analysis of ER, EP, HER2, and that the addition of other markers didn’t improve the prognosis estimates. The molecular profile may be a very useful instrument for breast cancer managing in countries with limited resorts.

Introdução: Resistência aos antirretrovirais pode limitar opções de tratamento, principalmente em pacientes com acúmulo de falhas terapêuticas, o que pode comprometer resultados clínicos. Objetivos: caracterizar o perfil de mutações na transcriptase reversa e protease do HIV-1 de pacientes em falha ao tratamento. Secundariamente, avaliar associação entre mutações e número de falhas terapêuticas, associação entre mutações e subtipos do HIV-1 e apresentar a evolução temporal da prevalência dos subtipos do HIV-1, no estado do Pará, ao Norte do Brasil. Método: Estudo transversal, no qual se avaliam genotipagens, entre janeiro de 2004 a dezembro de 2013, com dados obtidos de formulário de solicitação do exame padronizado pela RENAGENO e de impressos dos resultados, ambos arquivados em quatro serviços de atendimento especializados. Foram incluídos os testes realizados por laboratório da RENAGENO, em maiores de 18 anos, e o primeiro exame daqueles que o realizaram em mais de um momento, totalizando 377 amostras. As mutações são descritas de acordo com o banco de dados de resistência do HIV da Universidade de Stanford (http://hivdb.stanford.edu), estimam-se suas prevalências e avaliam-se mutações de resistência de acordo com o número de falhas no momento da genotipagem, bem como diferenças de mutações entre subtipos B e não-B do HIV-1. Resultados: A mutação M184V foi a mais prevalente (80,1%), seguida da K130N (40,6%) e TAM. Em pacientes multiexperimentados previamente à genotipagem, resistência a ZDV, d4T e TDF foi associada às mutações M41L, D67N, V118I, L210W, K219Q e T69D; bem como resistência a todos os IP/r associou-se às mutações principais M46I, V82A, L90M, I54V, I84V, M46L e L76V. O subtipo B é o predominante no Pará (90,7%) e diferenças de prevalência de mutações entre subtipos ocorreram entre as mutações L63P e A71T versus subtipo B, enquanto as mutações L76V, M36I, K20R, L10V, L89M e F53L associaram-se ao subtipo não-B. Conclusão: A seleção de mutações de resistência do HIV-1 relacionada aos antirretrovirais é similar ao descrito em literatura. O acúmulo de falhas ao tratamento favorece a emergência de mutações, o que reforça o monitoramento de falha virológica, seguida de genotipagem para minimizar o impacto de resistência. Estudos adicionais de epidemiologia molecular são necessários para avaliar melhor a questão da prevalência de subtipos de HIV-1 no estado e possíveis associações com mutações de resistência do HIV-1. / Introduction: Resistance to antiretroviral treatment can limit treatment options, especially in patients with accumulation of therapeutic failures, which may compromise clinical outcomes. Objectives: characterizing the profile of mutations in the protease and reverse transcriptase of HIV-1 patients in the treatment failure. Secondarily to evaluate the association between mutations and the number of treatment failures, association between mutations and subtypes of HIV-1 and present the temporal evolution of the prevalence of subtypes of HIV-1 in the state of Pará in northern Brazil. Method: cross-sectional study in which genotyping is evaluated between January, 2004 and December, 2013 with data obtained from the standardized application form for the examination RENAGENO and printed the results, both filed in four specialty care services. We included those by laboratory RENAGENO in 18 years and the first examination in those who underwent more than one time, totaling 377 samples. Mutations are described according to the database of HIV resistance at Stanford University (http://hivdb.stanford.edu), estimated their prevalence and resistance is evaluated according to the number of failures at the time of genotyping as well as differences between mutations and subtype B and non-B HIV-1. Results: The M184V mutation was the most prevalent (80.1%), followed by K130N (40.6%) and TAM. In patients who received at least three treatments prior to genotyping, resistance to ZDV, d4T and TDF was associated with mutations M41L, D67N, V118I, L210W, K219Q and T69D; well as resistance to all PI / r was associated with the major mutations M46I, V82A, L90M, I54V, I84V M46L and L76V. HIV-1 subtype B was the most prevalent (90.7%) and there were differences between subtypes B versus mutations: L63P and A71T were more frequent in the subtype B, whereas mutations L76V, K20R, L10V, L89M and F53L were in non-B subtypes. Conclusion: The selection of resistance mutations in HIV-1 related to antiretroviral is similar to that described in the literature. The accumulation of failures to treatment favors the emergence of mutations, reinforcing the monitoring and evaluation of virologic failure by genotyping to minimize the impact resistance. Additional molecular epidemiological studies are needed to better assess the issue of prevalence of subtypes of HIV-1 in the state and possible associations with resistance mutations in HIV-1.

Introdução: Resistência aos antirretrovirais pode limitar opções de tratamento, principalmente em pacientes com acúmulo de falhas terapêuticas, o que pode comprometer resultados clínicos. Objetivos: caracterizar o perfil de mutações na transcriptase reversa e protease do HIV-1 de pacientes em falha ao tratamento. Secundariamente, avaliar associação entre mutações e número de falhas terapêuticas, associação entre mutações e subtipos do HIV-1 e apresentar a evolução temporal da prevalência dos subtipos do HIV-1, no estado do Pará, ao Norte do Brasil. Método: Estudo transversal, no qual se avaliam genotipagens, entre janeiro de 2004 a dezembro de 2013, com dados obtidos de formulário de solicitação do exame padronizado pela RENAGENO e de impressos dos resultados, ambos arquivados em quatro serviços de atendimento especializados. Foram incluídos os testes realizados por laboratório da RENAGENO, em maiores de 18 anos, e o primeiro exame daqueles que o realizaram em mais de um momento, totalizando 377 amostras. As mutações são descritas de acordo com o banco de dados de resistência do HIV da Universidade de Stanford (http://hivdb.stanford.edu), estimam-se suas prevalências e avaliam-se mutações de resistência de acordo com o número de falhas no momento da genotipagem, bem como diferenças de mutações entre subtipos B e não-B do HIV-1. Resultados: A mutação M184V foi a mais prevalente (80,1%), seguida da K130N (40,6%) e TAM. Em pacientes multiexperimentados previamente à genotipagem, resistência a ZDV, d4T e TDF foi associada às mutações M41L, D67N, V118I, L210W, K219Q e T69D; bem como resistência a todos os IP/r associou-se às mutações principais M46I, V82A, L90M, I54V, I84V, M46L e L76V. O subtipo B é o predominante no Pará (90,7%) e diferenças de prevalência de mutações entre subtipos ocorreram entre as mutações L63P e A71T versus subtipo B, enquanto as mutações L76V, M36I, K20R, L10V, L89M e F53L associaram-se ao subtipo não-B. Conclusão: A seleção de mutações de resistência do HIV-1 relacionada aos antirretrovirais é similar ao descrito em literatura. O acúmulo de falhas ao tratamento favorece a emergência de mutações, o que reforça o monitoramento de falha virológica, seguida de genotipagem para minimizar o impacto de resistência. Estudos adicionais de epidemiologia molecular são necessários para avaliar melhor a questão da prevalência de subtipos de HIV-1 no estado e possíveis associações com mutações de resistência do HIV-1. / Introduction: Resistance to antiretroviral treatment can limit treatment options, especially in patients with accumulation of therapeutic failures, which may compromise clinical outcomes. Objectives: characterizing the profile of mutations in the protease and reverse transcriptase of HIV-1 patients in the treatment failure. Secondarily to evaluate the association between mutations and the number of treatment failures, association between mutations and subtypes of HIV-1 and present the temporal evolution of the prevalence of subtypes of HIV-1 in the state of Pará in northern Brazil. Method: cross-sectional study in which genotyping is evaluated between January, 2004 and December, 2013 with data obtained from the standardized application form for the examination RENAGENO and printed the results, both filed in four specialty care services. We included those by laboratory RENAGENO in 18 years and the first examination in those who underwent more than one time, totaling 377 samples. Mutations are described according to the database of HIV resistance at Stanford University (http://hivdb.stanford.edu), estimated their prevalence and resistance is evaluated according to the number of failures at the time of genotyping as well as differences between mutations and subtype B and non-B HIV-1. Results: The M184V mutation was the most prevalent (80.1%), followed by K130N (40.6%) and TAM. In patients who received at least three treatments prior to genotyping, resistance to ZDV, d4T and TDF was associated with mutations M41L, D67N, V118I, L210W, K219Q and T69D; well as resistance to all PI / r was associated with the major mutations M46I, V82A, L90M, I54V, I84V M46L and L76V. HIV-1 subtype B was the most prevalent (90.7%) and there were differences between subtypes B versus mutations: L63P and A71T were more frequent in the subtype B, whereas mutations L76V, K20R, L10V, L89M and F53L were in non-B subtypes. Conclusion: The selection of resistance mutations in HIV-1 related to antiretroviral is similar to that described in the literature. The accumulation of failures to treatment favors the emergence of mutations, reinforcing the monitoring and evaluation of virologic failure by genotyping to minimize the impact resistance. Additional molecular epidemiological studies are needed to better assess the issue of prevalence of subtypes of HIV-1 in the state and possible associations with resistance mutations in HIV-1.

Base teórica: Nas últimas décadas, o prognóstico do câncer inicial da mama tem sido baseado nas características clínicas das pacientes e em aspectos histológicos dos tumores. Nos últimos anos, subtipos moleculares de carcinoma de mama foram identificados através de estudos de perfil genético por “DNA microarray”. Esta nova classificação pode melhorar a avaliação prognóstica, porém ainda não está disponível e é de alto custo. A possibilidade de identificar subtipos moleculares através de métodos mais simples e de menor custo é particularmente importante em países com recursos limitados. A identificação de subtipos do câncer de mama é particularmente importante pelas implicações clínicas e pelas opções de tratamento. Métodos: Uma coorte retrospectiva de 71 pacientes consecutivas com carcinoma primário de mama de estágio clínico I e II, tratadas no Serviço de Mastologia do HCPA entre os anos de 1993 e 1997 com um seguimento mínimo de 5 anos.Foram revisados dados sobre características clínicas, histopatológicas, evolução clínica e desfechos apresentados no período. Foi realizada uma análise imunoistoquímica de blocos representativos dos tumores, avaliando-se o Receptor Estrogênico (RE), o Receptor de Progesterona (RP), o HER2, o Ki-67, o Bcl-2, o p53, o p63 e o CK8. Os objetivos foram determinar a prevalência do perfil molecular nesta população e em seus desfechos clínicos. Resultados: 39 tumores (54,9 %) foram luminal A; 15 tumores (21,1%) foram luminal B; 15 tumores (21,1) foram basais ou triplo negativos e somente 2 tumores (2,8%) foram HER2. Não houve diferença no prognóstico entre os subtipos de câncer de mama: luminal A (RH positivo e HER2 negativo); luminal B (RH positivo e HER2 positivo); HER2 (HER2 positivo) e basal (RH negativo, HER2 negativo) em relação à sobrevida livre de doença e à sobrevida global, embora apresentassem uma forte correlação com a diferenciação e com o grau tumoral. Provavelmente, isto se deve ao pequeno número de pacientes e ao prognóstico de pacientes com estágios iniciais da doença. Conclusões: Nossos resultados sugerem que é possível identificar os subtipos do câncer de mama pela análise imunoistoquímica de RE, RP e HER2, e que a adição de outros marcadores não melhora a estimativa de prognóstico. O perfil molecular pode ser um instrumento valioso para o manejo do câncer de mama em países com recursos limitados. / Background: In the last decades, prognostic evaluation of initial breast cancer is mostly based on patients’ clinical and tumoral histological features. Recently, molecular subtypes of invasive breast cancer were recognized through DNA microarray profiling studies. This new classification can potentially improve the prognostic evaluation but this technology is still not widely available and it’s too expensive. The possibility of identifying the molecular subtypes through simpler and cheaper methods is promising especially in countries with limited resorts. The identification of breast cancer subtypes is particularly important because it has clinical implications and for treatment options. Methods: A retrospective cohort of 71 consecutive patients with pathologic stage I or II primary breast carcinomas, treated in the HCPA Breast Unit, between 1993 and 1997 with a minimum follow up of 5 years , was studied. Histological and clinical features as well as clinical outcome and survival were reviewed. Immunohistochemical analysis was carried out in representative blocks of tumors with antibodies against Estrogen Receptor (ER),Progesterone Receptor (PR), Human Epidermal Growth Receptor – type 2 (HER2), Ki-67, Bcl-2, p53, p63 and CK8. The endpoints were to determine the prevalence the molecular portrait in this population and its clinical outcomes. Results: 39 tumors (54,9 %) were Luminal A, 15 tumors (21,1%) were Luminal B, 15 tumors (21,1) were Basal or triple negative and only 2 tumors (2,8%) were HER2. There was no prognostic difference among the breast cancer subtypes: luminal A (HR-positive and HER2 negative); luminal B (HR positive and HER2 positive); HER2 overexpressing (HER2 positive) and basal (HR negative, HER2 negative) relating to disease-free and overall survival, although there was a robust correlation with tumor grade and differentiation. This is probably related to limited number of patients in this study and prognosis of initial-stage patients. Conclusions: Our results suggest that it is possible to identify breast cancer subtypes by immunohistochemical analysis of ER, EP, HER2, and that the addition of other markers didn’t improve the prognosis estimates. The molecular profile may be a very useful instrument for breast cancer managing in countries with limited resorts.

The influence of cognitive organization, dysfunctional attitudes, and depressive "subtype" on the perceptions of negative life events is explored. BDI scores are used to delineate symptomatic and non-symptomatic groups. Construct content (sociotropic versus autonomous, as first defined by Beck) is used to identify predominant schema-type. Subjects completed a Problematic Situations Questionnaire with Dysfunctional Attitudes Scale. Results indicate that depressed individuals display more dysfunctional attitudes and negative affect in all types of negative situations; further the endorsement of dysfunctional attitudes is significantly more likely to occur in the context of schema-congruent situations. Findings are discussed a) in terms of the utility of personal constructs in the assessment of schema-type and b) in accordance with a person-event interactional model of depression.

The locus coeruleus (LC) is a putative site of action for angiotensin II in the brain. Immunocytochemical studies have identified angiotensin II-like immunoreactive material in nerve terminals innervating the LC, and the LC contains one of the highest densities of angiotensin II receptor binding sites in the rat brain. Recent studies using selective neurotoxins suggest that the binding sites for angiotensin II in the LC are present on noradrenergic perikarya. Angiotensin II receptors are now known to exist as two subtypes that are distinguishable both pharmacologically and biochemically. Radioligand binding studies using agonists and antagonists selective for these angiotensin II receptor subtypes indicate that the rat LC contains a mixture of the two known angiotensin II receptor subtypes, but that the PD123177-sensitive AIIβ receptor subtype is predominant. Comparisons of spontaneously hypertensive rats with normotensive rats indicates that angiotensin II and its receptors in the LC are elevated in the hypertensive rat strain. Studies of the biochemical and physiological actions of angiotensin II in the LC have not yet established an agreed-upon function for angiotensin II in this nucleus.

The non-peptide angiotensin II (AII) receptor subtype selective antagonist, DuP 753, was used to characterize AII receptor binding sites in the rat brain. DuP 753 competed for specific 125I-[Sar1, Ile8]AII (125I-SIAII) binding in many brain nuclei (IC50 = 20-30 nM), but was a weak competitor at remaining sites (IC50 > 10-4 M). DuP 753 sensitive binding sites (designated AIIα subtype) correspond with areas where binding is inhibited by sulfhydryl reducing agents, whereas DuP 753 insensitive sites (AIIβ) correspond with areas where binding is not inhibited by sulfhydryl reducing agents.

Introduction Breast cancer is the most common cancer among women in Sweden and world-wide. Immunohistochemical (IHC) expression of oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67 is routinely performed for diagnostic and prognostic purposes. Based on these biomarkers tumours are divided into subtypes: Luminal A, Luminal B, HER2-enriched and triple negative breast cancer (TNBC). There is evidence that tumour associated macrophages (TAMs) have a crucial role in tumour development. To identify TAMs the antibody CD163 can be used in immunohistochemical staining. Aim The aim of the study was to investigate differences in density of CD163+ macrophages among different subtypes of breast cancer. Material and method Formalin-fixed paraffin-embedded (FFPE) breast cancer tissue from the Biobank of Region Värmland was used. Tissue was de-identified before analysis. Groups were formed based on immunohistochemical expression of ER, PR and HER2, with the exclusion of the Luminal B group. Tissue was stained with CD163. Analysis was performed semi-quantitatively. The border between tumour and healthy tissue was assessed as well as the intra-tumoral tissue. Results At the tumour border, density of CD163+ macrophages was found to be lower in the Luminal group compared to both the HER2-enriched and TNBC.Within intra-tumoral tissue, the density of CD163+ macrophages was found to be lower in the Luminal compared to the HER2-enriched group. Conclusion The density of CD163+ macrophages is higher in HER-enriched and TNBC tumours compared to Luminal A breast cancer tumours.

No description available.

No description available.