CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior / A doenÃa de Chagas (DC) à considerada negligenciada sob vÃrios aspectos, dentre eles, por ser uma doenÃa que atinge pessoas de baixo nÃvel socioeconÃmico, pela falta de investimento em pesquisas para conhecer seu real panorama de prevalÃncia e pela limitada efetividade dos medicamentos disponÃveis. O presente estudo avaliou a soroprevalÃncia da infecÃÃo chagÃsica e o perfil sociodemogrÃfico de indivÃduos residentes no municÃpio de Limoeiro do Norte â CE, no perÃodo de abril a novembro de 2013. O estudo soroepidemiolÃgico foi realizado em 812 indivÃduos selecionados de forma aleatÃria incluindo habitantes locais, de ambos os sexos, com idade a partir de dois anos. Para atender aos objetivos, empregou-se o teste ELISA para pesquisa de anticorpos IgG anti-Trypanosoma cruzi e um questionÃrio semiestruturado para traÃar o perfil sociodemogrÃfico. As variÃveis do questionÃrio foram analisadas, por meio dos testes qui-quadrado ou exato de Fisher. Foram analisados 812 indivÃduos, dentre os quais 4,2% (34) apresentaram sorologia reagente para DC. As variÃveis sociodemogrÃficas que apresentaram associaÃÃo significativa com positividade para DC foram: idade maior que 50 anos (RP= 27,6; IC= 6,66-114,4; p= 0,000); escolaridade atà ensino fundamental incompleto (RP= 5,15; IC= 1,83-14,47; p= 0,000) e ocupaÃÃo aposentado (RP= 7,25; IC= 3,72- 14,14; p= 0,000). As condiÃÃes atuais de moradia dos participantes diagnosticados com infecÃÃo chagÃsica foram semelhantes Ãs dos nÃo infectados. A positividade para DC foi 6,17 vezes maior no grupo daqueles que jà residiram em casas de taipa (IC= 2,19â17,37). NÃo houve transmissÃo vertical nos indivÃduos estudados, uma vez que nenhum dos participantes, com mÃe chagÃsica, foi reagente para anticorpos anti-T. cruzi. NÃo houve associaÃÃo entre transfusÃes e positividade, indicando, que a transmissÃo se deu, possivelmente, por via vetorial nessa Ãrea. Dentre os indivÃduos infectados com T. cruzi, a maioria relatou ter algum problema de saÃde (p=0,000), sendo que a hipertensÃo arterial sistÃmica foi à Ãnica comorbidade, dentre as citadas, que mostrou associaÃÃo com a DC (p=0,000). Os indivÃduos com sorologia positiva predominaram, de maneira significativa, entre aqueles que vÃo mais de duas vezes ao mÃdico por ano (p=0,000) e que realizam algum tipo de exame com frequÃncia (p=0,025). Esse estudo possibilitou conhecer a soroprevalÃncia da infecÃÃo chagÃsica, o perfil sociodemogrÃfico dos infectados, verificar as variÃveis que tiveram associaÃÃo significativa com DC e beneficiar indivÃduos com o diagnÃstico precoce na fase crÃnica da infecÃÃo para que possam receber cuidados especÃficos. / Chagas disease (CD) is considered neglected in many aspects, among them, for being a disease that affects people of low socioeconomic status, for the lack of investment in research to characterize the real picture of its prevalence and for the limited effectiveness of available drugs. The present study evaluated the seroprevalence of T. cruzi infection and the sociodemographic profile of people living in the city of Limoeiro do Norte - CE in the period from April to November, 2013. The seroepidemiological study was conducted in 812 randomly selected individuals including local people of both sexes, aged at least 2 years. To meet the objectives, we used the ELISA test for IgG anti-Trypanosoma cruzi antibodies and a semi-structured questionnaire to find the sociodemographic profile. Questionnaire variables were analyzed using the chi-square or Fisher exact test. From the 812 individuals anlyzed, 4.2% (34) were seropositive for CD. The following sociodemographic variables were significantly associated with seropositivity for CD: age greater than 50 years (OR = 27.6, CI = 6.66 to 114.4, p = 0.000); incomplete primary education (PR = 5, 15 CI = 1.83 to 14.47, p = 0.000) and retired occupation (PR = 7.25, CI = 3.72 to 14.14, p = 0.000). The current housing conditions of the participants diagnosed with Chagas disease were similar to those uninfected. Seropositivity for CD was 6.17 times higher in the group of those who have lived in mud houses (CI = 2.19 to 17.37). There was no vertical transmission in the subjects studied, since none of the participants with Chagas-infected mother was reactive for anti-T. cruzi. There was no association between transfusions and seropositivity, indicating that vectorial transmission possibly occurred in this area. Among individuals infected with T. cruzi, most reported having at least one health problem (p = 0.000), and hypertension was the only comorbidity out of those cited that showed association with CD (p = 0.000). There was a significant predominance of seropositivity among those individuals that go to the doctor more than twice a year (p = 0.000) and perform some kind of test frequently (p = 0.025). This study brought us the seroprevalence of T. cruzi infection, the sociodemographic profile of those infected and the characteristics that were significantly associated with CD. Furthermore, the study allowed us to benefit individuals with early diagnosis in the chronic phase of the infection, so that they can receive specialized care.

The American Visceral Leishmaniasis (AVL) is endemic in tropical and subtropical regions of Latin America. In Brazil, in recent years has been expanding and building up. Historically, the state of Ceara has been presented in several cities a high prevalence of the disease, however, the city of Fortaleza, escaping this epidemiological pattern always reported low incidence of the disease, however, from 2005, showed an increase in the number of cases and spatial distribution, showing an expanding epidemic of the disease. The aim of this study was to evaluate the spatial and temporal distribution of disease incidence in the period 1995 to 2008. We analyzed the cases of AVL reported in SINAN and SIM, considering only patients in Fortaleza, who met the criteria adopted by the Ministry of Health for confirmation of diagnosis and the site of infection. The cases were georeferenced and analyzed based on the indicators: incidence and mortality and the following variables: dependent - confirmed cases of the disease and independent - age, age group, sex, place of residence, clinical manifestation, clinical course and type of diagnosis. We used spatial analysis techniques to analyze the cases. During the study period were recorded human cases of AVL 1267, of which 50% were younger than 4 years and 74 deaths. The year 2007 was presented the highest incidence of the disease. The highest incidence of cases were in males (64.3%). The average age of cases of AVL increased in epidemic period. The disease is clinically expressed differently in the epidemic phase, compared with the endemic phase. The risk of infection was higher in males than in females. Mortality was high only in the age group above 60 years. There was a significant increase in disease incidence in the elderly. Diagnostic tests showed high sensitivity and specificity. Over 70% of cases were confirmed through laboratory tests. We observed a decrease in cure rate and an increase in cases of co-infection with HIV. In the epidemic phase, spatial diffusion of disease was the kind of contagion. The diffusion process was linked to environmental factors and socioeconomic factors. We identified areas of high risk for the disease occurrence based on spatial analysis techniques. The study revealed the establishment of a new epidemiological pattern for kala-azar in Fortaleza, mainly characterized by the appearance of an emerging problem: the increase of cases of co-infection with HIV. Also revealed that environmental factors and socioeconomic factors were crucial in the processes of urbanization and expansion of the disease in the city. / A Leishmaniose Visceral Americana (LVA) à uma doenÃa endÃmica nas regiÃes tropicais e subtropicais da America Latina. No Brasil, nos Ãltimos anos, vem se expandindo e urbanizando-se. Historicamente, o Estado do Cearà tem apresentado, em diversos municÃpios, altas prevalÃncias da enfermidade; entretanto, a cidade de Fortaleza, fugindo desse padrÃo epidemiolÃgico sempre registrou baixa ocorrÃncia da doenÃa, no entanto, a partir de 2005, apresentou incremento significativo no nÃmero de casos e na distribuiÃÃo espacial, evidenciando uma expansÃo epidÃmica da doenÃa. O objetivo deste estudo foi avaliar a distribuiÃÃo espacial e temporal da incidÃncia da doenÃa, no perÃodo de 1995 a 2008. Foram analisados os casos de LVA notificados no SINAN e no SIM, considerando-se apenas os pacientes residentes em Fortaleza, que preenchiam os critÃrios adotados pelo MinistÃrio da SaÃde para confirmaÃÃo diagnÃstica e do local da infecÃÃo. Os casos foram georreferenciados e analisados com base nos indicadores: taxa de incidÃncia e letalidade e nas seguintes variÃveis: dependente â casos confirmados da doenÃa e independentes â sexo,faixa etÃria, grupo etÃrio, local de residÃncia, manifestaÃÃo clÃnica, evoluÃÃo clÃnica, tipo de diagnÃstico, tipo de tratament e escolaridade. Foram utilizadas tÃcnicas de anÃlise espacial para analisar os casos. No perÃodo do estudo foram registrados 1.267 casos humanos de LVA, dos quais 50% eram menores de 4 anos, e 74 Ãbitos. O ano de 2007 foi o que apresentou a maior taxa de incidÃncia da doenÃa. A maior ocorrÃncia de casos foi em indivÃduos do sexo masculino (64,3%). Houve mudanÃa de perfil da idade e da forma de expressÃo clÃnica da doenÃa na fase epidÃmica, comparada com a fase endÃmica. O risco de adoecer no sexo masculino foi maior do que no sexo feminino. A letalidade foi alta apenas na faixa etÃria acima dos 60 anos. Houve um crescimento significativo na incidÃncia da doenÃa em pessoas idosas. Os exames diagnÃsticos apresentaram alta sensibilidade e especificidade. Mais de 70% dos casos foram confirmados por critÃrio laboratorial. Foi observada uma queda na taxa de cura e um aumento dos casos de co-infecÃÃo por HIV. Na fase epidÃmica, a difusÃo espacial da doenÃa foi do tipo por contÃgio. O processo de difusÃo esteve associado aos fatores ambientais e socioeconÃmicos. Foram identificadas as Ãreas de alto risco para a ocorrÃncia da doenÃa com base nas tÃcnicas de anÃlise espacial. O estudo revelou o estabelecimento de um novo padrÃo epidemiolÃgico para o calazar em Fortaleza, caracterizado principalmente pelo surgimento de um problema emergente: o incremento de casos de co-infecÃÃo por HIV. Revelou, ainda, que os fatores ambientais e socioeconÃmicos foram determinantes nos processos de urbanizaÃÃo e expansÃo da doenÃa na cidade.

Il carcinoma squamoso orale (CSO) è spesso preceduto da lesioni definite potenzialmente maligne tra cui la leucoplachia e il lichen ma una diagnosi precoce avviene ancora oggi in meno della metà dei casi. Inoltre spesso un paziente trattato per CSO svilupperà secondi tumori. Scopo del lavoro di ricerca è stato: 1) Studiare, mediante metodica di next generation sequencing, lo stato di metilazione di un gruppo di geni a partire da prelievi brushing del cavo orale al fine di identificare CSO o lesioni ad alto rischio di trasformazione maligna. 2) Valurare la relazione esistente tra sovraespressione di p16INK4A e presenza di HPV in 35 pazienti affetti da lichen 3) Valutare la presenza di marker istopatologici predittivi di comparsa di seconde manifestazioni tumorali 4) valutare la relazione clonale tra tumore primitivo e metastasi linfonodale in 8 pazienti mediante 2 metodiche di clonalità differenti: l’analisi di mtDNA e delle mutazioni del gene TP53. I risultati hanno mostrato: 1) i geni ZAP70 e GP1BB hanno presentato un alterato stato di metilazione rispettivamente nel 100% e nel 90,9% di CSO e lesioni ad alto rischio, mentre non sono risultati metilati nei controlli sani; ipotizzando un ruolo come potenziali marcatori per la diagnosi precoce nel CSO. 2)Una sovraespressione di p16INK4A è risultata in 26/35 pazienti affetti da lichen ma HPV-DNA è stato identificato in soli 4 campioni. Nessuna relazione sembra essere tra sovraespressione di p16INK4A e virus HPV. 3)L’invasione perineurale è risultato un marker predittivo della comparsa di recidiva locale e metastasi linfonodale, mentre lo stato dei margini chirurgici si è rilevato un fattore predittivo per la comparsa di secondi tumori primitivi 4) Un totale accordo nei risultati c’è stato tra analisi di mtDNA e analisi di TP53 e le due metodiche hanno identificato la presenza di 4 metastasi linfonodali non clonalmente correlate al tumore primitivo. / Oral Squamous Cell Carcinoma (OSCC) is often preceded by Potentially Malignant Lesions, Leukoplakia and Lichen Planus (LP), but still today is usually diagnosed in advanced stage. Additionally patients treated for OSCC have a good chance to develop a second primary OSCC. The purpose of the research was: 1) to assess, by bisulfite Next Generation Sequencing, the methylation status of a list of candidate genes obtained from oral brushing specimens to early detect OSCC using non-invasive procedures. 2) to yield more insights into the relationship between p16INK4A over-expression and the presence of HPV-DNA in 35 LP samples. 3) to identify the clinicopathologic parameters significantly related to a second loco-regional event in a population of 180 patients treated for primary OSCC 4) to evaluate the relationship between primary OSCC and lymph node metastasis in 8 patients using two different 2 clonality tests: mt-DNA D-loop and TP53 sequence analysis. The results showed that: 1) ZAP70 and GP1BB showed an aberrant methylation status respectively in 100% and 90,9% of OSCC and High Risk lesions, while resulted unmethylated in normal healthy donors. DNA methylation analysis of GP1BB and ZAP70 seems to be a promising non invasive tool to early detect OSCC from oral brushing specimens. 2) p16INK4A over-expression was found in 26/35 LP samples, whereas HPV was found in 4/35 lesions: 3 low-risk HPV and 1 high-risk HPV. P16INK4A overexpression is not correlated with HPV in patients with LP. 3) Perineural invasion was significantly related to lymph-node metastasis (18% vs 8%) and Local Recurrence (15% vs 5%), while the status of the surgical margin resulted an independent factor influencing Second Primary Tumor. 4) The results from mtDNA analysis showed a good agreement with results of p53 mutation analysis and revealed the presence of 4/11 neck nodal metastases not phylogenetically related respect to primary tumor.

Fifty-two cases of monomorphic post-transplant lymphoproliferative disorders (M-PTLD), developed in patients undergone solid organ or bone marrow transplantation, were studied by the application of the tissue micro-array (TMA) technology. They included 50 cases of diffuse large B-cell lymphomas (DLBCL) and 2 Burkitt lymphomas (BL). In order to evaluate the immune-profile a large panel of antibodies was applied including several new markers (Cyclin D2, Cyclin D3, p27, PKC-β, FOXP-1 and Survivin) identified as negative prognostic factors in DLBCL of the immunocompetent patient. Out of 50 DLBCL, 23 cases (46%) had an Activated B Cell (ABC) phenotype, 8 (16%) a Germinal Centre B-cell (GCB) phenotype, and 11 (22%) an Unclassified (UC) phenotype. In 8 cases (16%) the subtype was not demonstrable due to sub-optimal preservation or loss of the tissue core. FISH analysis detected BCL2 gene amplification and MYC rearrangement. EBV was identified in 32 cases (64%) performing immunohistochemistry (LMP-1) and in situ hybridization (EBER). Clinical data and follow-up were available in all cases of malignant lymphomas but one. Thirty-two patients died for progression of disease or complications related to transplant (bleeding, bacterial infections, and multi-organ failure); 17 patients are actually alive and disease-free. M-PTLD are aggressive lymphomas characterized by very poor outcome. The neoplastic process is stimulated by a prolonged immunosuppressive status which is capable to induce alterations of the immune system and allow EBV reactivation in previously infected patients. Indeed EBV infection seems to be the most significant risk factor to predict the development of a PTLD while age, sex, site of involvement and type of transplant do not have significant correlation. Furthermore DLBCL arisen in a setting of immunodeficiency share phenotypic and molecular features with DLBCL of the immunocompetent patient. In particular, the former shows a high incidence of BCL2 gene amplification and this aberration typically correlates with “non-GCB” phenotype. Also M-PTLD do express prognostic markers (PKC-β, cyclin D2, FOXP-1, and Survivin): notably, in our study, PKC-β and FOXP-1 were frequently expressed and they were predictive of a shorter overall survival even in lymphomas recognized to have a good prognosis (GCB-type). Given the fact that such molecules are detectable at the time of the diagnosis, we postulate whether a “tailored” or more specific therapy might be applied in the management of the immune-compromised patient.

No description available.

Recent reports showed that early-interim PET-scan is the only tool predicting treatment outcome in advanced-stage classical Hodgkin lymphoma (asCHL). We evaluated the prognostic impact of a series of immunohistochemical markers, mentioned in literature as prognostic factors, on tissue microarrays assembled from biopsies of 220 patients: STAT1, SAP, TOP2A, PCNA and CD20, both in neoplastic (HRSC) and microenvironment cells (MC); RRM2, MAD2, CDC2, BCL2, P53, BCL11A and EBER in HRSC; ALDH1A1, TIA-1, granzyme B, perforin, FOXP3, and PD-1 in MC. All patients had been treated with standard ABVD ± Rx therapy. Interim-PET after 2 ABVD courses was evaluated according to the criteria indicated by Gallamini in his study (Journal of Clinical Oncology, 2007). The survival analysis has been performed in a subset of 138 patients whose complete clinical information were available: the mean age was 33.3 years (14-79), the stage III-IVB in 98 and IIB in 40, and the mean follow-up 38.1 months (7.6-71.9). Histopathology review showed: NS-I 75, NS-II 22, MC 20, DL 3, and CHL/nos 18 cases. Interim-PET was positive in 30 patients, while treatment failure was recorded in 32. In univariate analysis the factors related to treatment outcome were BCL2 on HRSC (cut-off value 50%), STAT1/SAP on MC, and PET (Log-rank 6.9, 7.9 and 93.9 respectively). The combined expression of STAT1 and SAP was scored in three levels depending on the architectural pattern: score 0 for expression of both with a diffuse/rosetting pattern; score 1 for discordant combination of diffuse/rosetting and scattered patterns; score 2 for both markers with a scattered pattern; the 3y-PFS were 87.4%, 69.9% and 61.9% respectively. In multivariate analysis PET, BCL2 and STAT1/SAP remained significant (HR: 24.8, 4.6, 7.5 and 5.6, respectively; p<.01). The proposed model is able to predict treatment response in AsCHL, even if with a lower efficacy than PET. However, unlike PET, it can be applied upfront therapy.

Gliomas are the most common primary brain tumours. Despite advances in surgical techniques, postoperative supportive care, radiation and adjuvant systemic therapy, the life expectancy of patients with high grade glioma has remained essentially poor. Furthermore differential diagnosis among astrocytomas, oligodendrogliomas and oligoastrocytomas is very challenging and subject to inter-observer variability. The purpose of the research was: 1) to investigate a series of high grade and low grade gliomas at gene and protein (immunohistochemistry) levels to disclose possible genetic portraits of malignancy; 2) to verify the utility of Nogo-A, Olig-2 and synaptophysin in providing a correct histological diagnosis of oligodendroglioma and to investigate a possible complementary role in selecting the best areas suitable for detecting 1p/19q codeletion using FISH analysis; 3) to study the role of microRNA in high grade gliomas. In order to obtain these goals large series of brain tumors were studied with DNA microarrays, immunohistochemistry and RT-PCR The results demonstrated that: - Overexpression of IGFBP-2 and CDC20 is highly related to glioblastomas and their immunopositivity can be useful for the identification of glioblastoma in small biopsies. - Nogo-A is the most useful and specific marker in differentiating oigodendrogliomas from other gliomas. Furthermore, using a Nogo-A driven FISH analysis, it is possible to identify a larger number of 1p19q codeletions in gliomas. - microRNAs can be studied in paraffin embedded tissues better than in fresh tissues. A series of six microRNA, significatively deregulated in glioblastomas, may represent a genetic signature with prognostic and predictive value and could constitute candidates for novel anti-cancer therapeutics.

No description available.

I linfomi a cellule T periferiche rappresentano circa il 12% di tutte le neoplasie linfoidi.In questo studio, abbiamo effettuato un’analisi di miRNA profiling (TaqMan Array MicroRNA Cards A) su 60 campioni FFPE suddivisi in: PTCLs/NOS (N=25), AITLs (N=10), ALCLs (N=12) e cellule T normali (N=13). Abbiamo identificato 4 miRNA differenzialmente espressi tra PTCLs e cellule T normali. Inoltre, abbiamo identificato tre set di mirna che discriminano le tre entita di PTCLs nodali / AIMs: Here, we performed an extensive miRNA profiling of PTCLs in order to identify differentially expressed miRNA, either involved in their pathogenesis or potentially useful for their differential diagnosis. Methods: We studied by miRNA profiling (TaqMan Array MicroRNA Cards A) 60 samples including PTCLs/NOS (N=25), AITLs (N=10), ALCLs (N=12) and normal T cells (N=13); in addition, 40 independent PTCL cases were studied by qRT-PCR as validation. We assess a GEP and miRNA Profiling. Findings: we identified 256 miRNA differentiating the two groups. In conclusion, miRNA profiling allowed to identify miRNA possibly involved in PTCL pathogenesis and to develop a novel diagnostic tool for the differential diagnosis of the commonest subtypes.

Traditional morphological examinations are not anymore sufficient for a complete evaluation of tumoral tissue and the use of neoplastic markers is of utmost importance. Neoplastic markers can be classified in: diagnostic, prognostic and predictive markers. Three markers were analyzed. 1) Insulin-like growth factor binding protein 2 (IGFBP2) was immunohistochemically examined in prostatic tissues: 40 radical prostatectomies from hormonally untreated patients with their preoperative biopsies, 10 radical prostatectomies from patients under complete androgen ablation before surgery and 10 simple prostatectomies from patients with bladder outlet obstruction. Results were compared with α-methylacyl-CoA racemase (AMACR). IGFBP2 was expressed in the cytoplasm of untreated adenocarcinomas and, to a lesser extent, in HG-PIN; the expression was markedly lower in patients after complete androgen ablation. AMACR was similarly expressed in both adenocarcinoma and HG-PIN, the level being similar in both lesions; the expression was slightly lower in patients after complete androgen ablation. IGFBP2 may be used a diagnostic marker of prostatic adenocarcinomas. 2) Heparan surface proteoglycan immunohistochemical expression was examined in 150 oral squamous cell carcinomas. Follow up information was available in 93 patients (range: 6-34 months, mean: 19±7). After surgery, chemotherapy was performed in 8 patients and radiotherapy in 61 patients. Multivariate and univariate overall survival analyses showed that high expression of syndecan-1 (SYN-1) was associated with a poor prognosis. In patients treated with radiotherapy, such association was higher. SYN-1 is a prognostic marker in oral squamous cell carcinomas; it may also represent a predictive factor for responsiveness to radiotherapy. 3) EGFR was studied in 33 pulmonary adenocarcinomas with traditional DNA sequencing methods and with two mutation-specific antibodies. Overall, the two antibodies had 61.1% sensitivity and 100% specificity in detecting EGFR mutations. EGFR mutation-specific antibodies may represent a predictive marker to identify patients candidate to tyrosine kinase inhibitors therapy.