RESUMEN
Germ cell tumors (GCTs) constitute diverse neoplasms arising in the gonads or extragonadal locations. Testicular GCTs (TGCTs) are the predominant solid tumors in adolescents and young men. Despite cisplatin serving as the primary therapeutic intervention for TGCTs, 1020% of patients with advanced disease demonstrate resistance to cisplatinbased chemotherapy, and epithelialmesenchymal transition (EMT) is a potential contributor to this resistance. EMT is regulated by various factors, including the snail family transcriptional repressor 2 (SLUG) transcriptional factor, and, to the best of our knowledge, remains unexplored within TGCTs. Therefore, the present study investigated the EMT transcription factor SLUG in TGCTs. In silico analyses were performed to investigate the expression of EMT markers in TGCTs. In addition, a cisplatinresistant model for TGCTs was developed using the NTERA2 cell line, and a mouse model was also established. Subsequently, EMT was assessed both in vitro and in vivo within the cisplatinresistant models using quantitative PCR and western blot analyses. The results of the in silico analysis showed that the different histologies exhibited distinct expression profiles for EMT markers. Seminomas exhibited a lower expression of EMT markers, whereas embryonal carcinomas and mixed GCT demonstrated high expression. Notably, patients with lower SLUG expression had longer median progressionfree survival (46.4 months vs. 28.0 months, P=0.022). In the in vitro analysis, EMTassociated genes [fibronectin; vimentin (VIM); actin, α2, smooth muscle; collagen type I α1; transforming growth factorß1; and SLUG] were upregulated in the cisplatinresistant NTERA2 (NTERA2R) cell line after 72 h of cisplatin treatment. Consistent with this finding, the NTERA2R mouse model demonstrated a significant upregulation in the expression levels of VIM and SLUG. In conclusion, the present findings suggested that SLUG may serve a crucial role in connecting EMT with the development of cisplatin resistance, and targeting SLUG may be a putative therapeutic strategy to mitigate cisplatin resistance.
Asunto(s)
Cisplatino , Resistencia a Antineoplásicos , Transición Epitelial-Mesenquimal , Neoplasias de Células Germinales y Embrionarias , Factores de Transcripción de la Familia Snail , Neoplasias Testiculares , Adulto , Animales , Humanos , Masculino , Ratones , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Cisplatino/farmacología , Cisplatino/uso terapéutico , Modelos Animales de Enfermedad , Transición Epitelial-Mesenquimal/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias de Células Germinales y Embrionarias/metabolismo , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias de Células Germinales y Embrionarias/genética , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Factores de Transcripción de la Familia Snail/metabolismo , Factores de Transcripción de la Familia Snail/genética , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/patología , Neoplasias Testiculares/genética , Neoplasias Testiculares/tratamiento farmacológico , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
microRNAs (miRNAs) are small endogenous noncoding RNAs, and alterations in their expression may contribute to oncogenesis. Discovering a unique miRNA pattern holds the potential for early detection and novel treatment possibilities in cancer. This study aimed to evaluate miRNA expression in pediatric patients with gonadal germ cell tumors (GCTs), focusing on characterizing the miRNA profiles of each histological subtype and identifying a distinct histological miRNA signature for a total of 42 samples of pediatric gonadal GCTs. The analysis revealed distinct miRNA expression profiles for all histological types, regardless of the primary site. We identified specific miRNA expression signatures for each histological type, including 34 miRNAs for dysgerminomas, 13 for embryonal carcinomas, 25 for yolk sac tumors, and one for immature teratoma, compared to healthy controls. Furthermore, we identified 26 miRNAs that were commonly expressed in malignant tumors, with six miRNAs (miR-302a-3p, miR-302b-3p, miR-371a-5p, miR-372-3p, miR-373-3p, and miR-367-3p) showing significant overexpression. Notably, miR-302b-3p exhibited a significant association with all the evaluated clinical features. Our findings suggest that miRNAs have the potential to aid in the diagnosis, prognosis, and management of patients with malignant GCTs.
Asunto(s)
Biomarcadores de Tumor , Regulación Neoplásica de la Expresión Génica , MicroARNs , Neoplasias de Células Germinales y Embrionarias , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias de Células Germinales y Embrionarias/genética , Neoplasias de Células Germinales y Embrionarias/metabolismo , Neoplasias de Células Germinales y Embrionarias/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Niño , Masculino , Femenino , Adolescente , Preescolar , Perfilación de la Expresión Génica , Lactante , Neoplasias Testiculares/genética , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/patologíaRESUMEN
Ovarian germ cell tumors (OGCTs) are rare in adults; indeed, they occur predominantly in children, adolescents, and young adults, and they account for approximately 11% of cancer diagnoses in these groups. Because OGCTs are rare tumors, our current understanding of them is sparse; this is because few studies have investigated the molecular basis of pediatric and adult cancers. Here, we review the etiopathogenesis of OGCTs in children and adults, and we address the molecular landscape of these tumors, including integrated genomic analysis, microRNAs, DNA methylation, the molecular implications of treatment resistance, and the development of in vitro and in vivo models. An elucidation of potential molecular alterations may provide a novel field for understanding the pathogenesis, tumorigenesis, diagnostic markers, and genetic peculiarity of the rarity and complexity of OGCTs.
RESUMEN
(1) BRAF mutations are associated with high mortality and are a substantial factor in therapeutic decisions. Therapies targeting BRAF-mutated tumors, such as vemurafenib (PLX), have significantly improved the overall survival of melanoma patients. However, patient relapse and low response rates remain challenging, even with contemporary therapeutic alternatives. Highly proliferative tumors often rely on glycolysis to sustain their aggressive phenotype. 3-bromopyruvate (3BP) is a promising glycolysis inhibitor reported to mitigate resistance in tumors. This study aimed to evaluate the potential of 3BP as an antineoplastic agent for PLX-resistant melanoma treatment. (2) The effect of 3BP alone or in combination with PLX on viability, proliferation, colony formation, cell death, migration, invasion, epithelial-mesenchymal marker and metabolic protein expression, extracellular glucose and lactate, and reactive species were evaluated in two PLX-resistant melanoma cell lines. (3) 3BP treatment, which was more effective as monotherapy than combined with PLX, disturbed the metabolic and epithelial-mesenchymal profile of PLX-resistant cells, impairing their proliferation, migration, and invasion and triggering cell death. (4) 3BP monotherapy is a potent metabolic-disrupting agent against PLX-resistant melanomas, supporting the suppression of the malignant phenotype in this type of neoplasia.
Asunto(s)
Melanoma , Recurrencia Local de Neoplasia , Humanos , Vemurafenib/farmacología , Vemurafenib/uso terapéutico , Línea Celular Tumoral , Melanoma/patología , Fenotipo , Proteínas Proto-Oncogénicas B-raf/genética , Resistencia a Antineoplásicos/genética , Mutación , Inhibidores de Proteínas Quinasas/farmacologíaRESUMEN
BACKGROUND: Testicular germ cell tumors (TGCTs), a group of heterogeneous neoplasms, are the most frequent tumors of teenagers and young men, with the incidence rising worldwide. High cure rates can be achieved through cisplatin (CDDP)-based treatment, but approximately 10% of patients present refractory disease and virtually no treatment alternatives. Here, we explored new strategies to treat CDDP-resistant. METHODS: In vitro TGCT CDDP-resistance model was established and differential mRNA expression profiles were evaluated using NanoString technology. Then, TGCT cell lines were treated with four potential drugs (PCNA-I1, ML323, T2AA, and MG-132) to overcome CDDP-resistance. RESULTS: We found several differentially expressed genes related to DNA repair and cell cycle regulation on CDDP-resistant cell line (NTERA-2R) compared to parental cell line (NTERA-2P), and the proteasome inhibitor MG-132 demonstrated cytotoxic activity in all cell lines evaluated, even at a nanomolar range. MG-132 also enhanced cell lines' sensitivity to CDDP, increasing apoptosis in both NTERA-2P and NTERA-2R. CONCLUSIONS: MG-132 emerges as a potential new drug to treat CDDP-resistant TGCT. Targeted therapy based on molecular mechanism insights may contribute to overcome acquired chemotherapy CDDP-resistance.
Asunto(s)
Antineoplásicos , Neoplasias de Células Germinales y Embrionarias , Adolescente , Antineoplásicos/farmacología , Línea Celular Tumoral , Cisplatino/farmacología , Cisplatino/uso terapéutico , Resistencia a Antineoplásicos/genética , Humanos , Masculino , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/genética , Neoplasias TesticularesRESUMEN
Cancer is a leading cause of death by disease in children and the second most prevalent of all causes in adults. Testicular germ cell tumors (TGCTs) make up 0.5% of pediatric malignancies, 14% of adolescent malignancies, and are the most common of malignancies in young adult men. Although the biology and clinical presentation of adult TGCTs share a significant overlap with those of the pediatric group, molecular evidence suggests that TGCTs in young children likely represent a distinct group compared to older adolescents and adults. The rarity of this cancer among pediatric ages is consistent with our current understanding, and few studies have analyzed and compared the molecular basis in childhood and adult cancers. Here, we review the major similarities and differences in cancer genetics, cytogenetics, epigenetics, and chemotherapy resistance between pediatric and adult TGCTs. Understanding the biological and molecular processes underlying TGCTs may help improve patient outcomes, and fuel further investigation and clinical research in childhood and adult TGCTs.
RESUMEN
Human multipotent mesenchymal stromal cells (MSCs) display immunoregulatory functions that can modulate innate and adaptive cellular immune responses. The suppressive and immunomodulatory activities of MSCs occur through the action of soluble factors that are constitutively produced and released by these cells or, alternatively, after MSC induction by stimuli of inflammatory microenvironments. However, to date the contribution of MSCs in the inflammatory microenvironment resulting from viral infection is unknown. In our study, we evaluated the MSC immunosuppressive effect on human T lymphotropic virus type 1 (HTLV-1) infected T lymphocytes. To evaluate if MSC immunoregulation can influence the proliferation of HTLV-1 infected T lymphocytes, we compared the proliferation of lymphocytes obtained from HTLV-1 infected and healthy individuals cocultured in the presence of MSCs. It was observed that the lymphoproliferative inhibition by MSCs on infected lymphocytes was similar compared to the cells obtained from healthy individuals. In addition, this suppressive effect was related to a significant increase of indoleamine-2,3-dioxygenase and prostaglandin E2 gene expression (p ≤ .05). Furthermore, the HTLV-1 pol gene was less expressed after coculturing with MSCs, suggesting that the MSC immunoregulation can have effective suppression on HTLV-1 infected T cells. In conclusion, this study suggests that MSCs could be involved in the immunomodulation of the HTLV-1 infected T lymphocytes.
Asunto(s)
Infecciones por HTLV-I/inmunología , Inmunomodulación , Células Madre Mesenquimatosas/inmunología , Linfocitos T/inmunología , Adulto , Diferenciación Celular , Células Cultivadas , Técnicas de Cocultivo , Femenino , Virus Linfotrópico T Tipo 1 Humano/genética , Humanos , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Linfocitos T/virología , Proteínas Virales/genéticaRESUMEN
INTRODUCTION: American tripanosomiasis (Chagas disease), the second most neglected disease in the world, is caused by the protozoan parasite Trypanosoma cruzi. Though natural transmission by insect vectors has been controlled, there is significant risk of T. cruzi transmission by blood transfusion in non-endemic regions, generally due to immigration processes from endemic areas. METHODOLOGY: The objective of this study was to evaluate anti-T. cruzi seroprevalence in blood donors from the western part of São Paulo State, Brazil, by serologic and immunofluorescence confirmation tests for the period between 2012 and 2014. Currently, this region is regarded as a non-endemic area for Chagas disease. RESULTS: The confirmed overall T. cruzi seroprevalence among blood donors was 0.10%, which can be considered low compared to other Brazilian regions. Nevertheless, the distribution of the anti-T. cruzi antibodies within the examined region was uneven, and some areas of significantly higher prevalence were observed. CONCLUSIONS: We could consider two tendencies in the prevalence of T. cruzi: (i) residual older undiagnosed cases from São Paulo State, and (ii) immigration from endemic Brazilian or South American regions. The discordance obtained for T. cruzi prevalence by serologic and immunofluorescence methods demonstrates that more specific routine diagnosis is needed to diminish the cost of the assays and the loss of blood supply once all seropositive blood bags are immediately discarded.
Asunto(s)
Anticuerpos Antiprotozoarios/sangre , Donantes de Sangre , Enfermedad de Chagas/epidemiología , Trypanosoma cruzi/inmunología , Adolescente , Adulto , Anciano , Brasil/epidemiología , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Masculino , Persona de Mediana Edad , Estudios Seroepidemiológicos , Pruebas Serológicas , Adulto JovenRESUMEN
Chronic Myeloid Leukemia (CML), Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF) are Myeloproliferative Neoplasms (MPN) characterized by clonal myeloproliferation without cell maturation impairment. CML pathogenesis is associated with the Ph chromosome leading to BCR-ABL tyrosine-kinase constitutive expression. The Ph negative MPN (PV, ET and PMF) are characterized by the mutation JAK2(V617F) of the JAK2 protein in the auto-inhibitory JH2 domain, which is found in most PV patients and in approximately half of ET and PMF patients. Considerable effort is being made to understand the role of JAK2(V617F) at the MPN initiation and to clarify the pathogenesis and apoptosis resistance in CML, PV, ET and PMF patients. In the present investigation, we evaluated the Death Inducer-Obliterator (DIDO) (variants DIDO 1, 2 and 3) levels in CML, PV, ET and PMF patients. Our data reported the DIDO 1, 2 and 3 differential expressions in Myeloproliferative Neoplasms.
Asunto(s)
Proteínas de Unión al ADN/análisis , Variación Genética , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Trastornos Mieloproliferativos/patología , Adulto , Anciano , Proteínas de Unión al ADN/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Janus Quinasa 2/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Masculino , Persona de Mediana Edad , Trastornos Mieloproliferativos/genética , Policitemia Vera , Mielofibrosis Primaria , Trombocitemia Esencial , Adulto JovenRESUMEN
INTRODUCTION: Human T-lymphotropic virus types 1/2 (HTLV-1/2) are distributed worldwide and are endemic in specific regions. METHODS: Serological evaluation of the HTLV-1/2 prevalence and co-infection rate [human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), Chagas disease, and syphilis)] for 2011-2014 was performed with volunteer blood donors from the western part of São Paulo State. RESULTS: Serrana and Araçatuba had higher HTLV seroprevalence rates (0.1%); while Franca, Olimpia, and Bebedouro had lower seroprevalences (0.04%). Co-infection (HBV and syphilis) was present in 12.3% of HTLV-infected blood donors. CONCLUSIONS: Our findings provide data for the prevalence of HTLV in Brazil and demonstrate the importance of regional and global hemovigilance.
Asunto(s)
Donantes de Sangre/estadística & datos numéricos , Coinfección/epidemiología , Infecciones por HTLV-I/epidemiología , Infecciones por HTLV-II/epidemiología , Adulto , Brasil/epidemiología , Enfermedad de Chagas/epidemiología , Femenino , Infecciones por VIH/epidemiología , Hepatitis B/epidemiología , Hepatitis C/epidemiología , Humanos , Persona de Mediana Edad , Prevalencia , Sífilis/epidemiologíaRESUMEN
ABSTRACT Human T-lymphotropic virus type 1 (HTLV-1) is a human retrovirus related to the chronic neuroinflammatory disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). CD4+ T cells activation appears to play a key role on HTLV-1 infection. Here we investigated the expression of genes associated to T cell activation CD3e molecule, epsilon (CD3?), lymphocyte-specific protein tyrosine kinase (LCK), vav 1 guanine nucleotide exchange factor (VAV1), and zeta-chain (TCR) associated protein kinase 70 kDa (ZAP70) on T lymphocytes of HTLV-1-infected individuals and compared to healthy uninfected individuals (CT). We observed that CD3?, LCK, ZAP70, and VAV1 gene expression were increased in CD4+ T cells from HAM/TSP group compared to HTLV-1 asymptomatic patients (HAC). Moreover, ZAP70 and VAV1 were also upregulated in HAM/TSP compared to CT group. We detected a positive correlation among all these genes. We also observed that CD3?, LCK, and VAV1 genes had a positive correlation with the proviral load (PVL) and Tax expression. These results suggest that PVL and Tax protein could drive CD3?, LCK, and VAV1 gene expression in CD4+ T cells, and these genes function on a synchronized way on the CD4+ T cell activation. The elucidation of the mechanisms underlying T cell receptor signaling pathway is of considerable interest and might lead to new insights into the mechanism of HAM/TSP.
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , /inmunología , Perfilación de la Expresión Génica , Paraparesia Espástica Tropical/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Transducción de Señal/inmunología , /metabolismo , Estudios de Casos y Controles , /enzimología , /virología , Expresión Génica , Paraparesia Espástica Tropical/genética , Proteínas Tirosina Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-vav/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Linfocitos T/metabolismo , Carga Viral , /metabolismoRESUMEN
Human T-lymphotropic virus type 1 (HTLV-1) is a human retrovirus related to the chronic neuroinflammatory disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). CD4(+) T cells activation appears to play a key role on HTLV-1 infection. Here we investigated the expression of genes associated to T cell activation CD3e molecule, epsilon (CD3É), lymphocyte-specific protein tyrosine kinase (LCK), vav 1 guanine nucleotide exchange factor (VAV1), and zeta-chain (TCR) associated protein kinase 70kDa (ZAP70) on T lymphocytes of HTLV-1-infected individuals and compared to healthy uninfected individuals (CT). We observed that CD3É, LCK, ZAP70, and VAV1 gene expression were increased in CD4(+) T cells from HAM/TSP group compared to HTLV-1 asymptomatic patients (HAC). Moreover, ZAP70 and VAV1 were also upregulated in HAM/TSP compared to CT group. We detected a positive correlation among all these genes. We also observed that CD3É, LCK, and VAV1 genes had a positive correlation with the proviral load (PVL) and Tax expression. These results suggest that PVL and Tax protein could drive CD3É, LCK, and VAV1 gene expression in CD4(+) T cells, and these genes function on a synchronized way on the CD4(+) T cell activation. The elucidation of the mechanisms underlying T cell receptor signaling pathway is of considerable interest and might lead to new insights into the mechanism of HAM/TSP.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Perfilación de la Expresión Génica , Paraparesia Espástica Tropical/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Transducción de Señal/inmunología , Adulto , Anciano , Complejo CD3/metabolismo , Linfocitos T CD4-Positivos/enzimología , Linfocitos T CD4-Positivos/virología , Estudios de Casos y Controles , Femenino , Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Paraparesia Espástica Tropical/genética , Proteínas Tirosina Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-vav/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Linfocitos T/metabolismo , Carga Viral , Proteína Tirosina Quinasa ZAP-70/metabolismoRESUMEN
The typical characteristics of mesenchymal stem cells (MSCs) can be affected by inflammatory microenvironment; however, the exact contribution of HTLV-1 to MSC dysfunction remains to be elucidated. In this study, we demonstrated that MSC cell surface molecules VCAM-1 and ICAM-1 are upregulated by contact with HTLV-1, and HLA-DR was most highly expressed in MSCs co-cultured with MT2 cells. The expression levels of VCAM-1 and HLA-DR were increased in MSCs cultured in the presence of PBMCs isolated from HTLV-1-infected symptomatic individuals compared with those cultured with cells from asymptomatic infected individuals or healthy subjects. HTLV-1 does not impair the MSC differentiation process into osteocytes and adipocytes. In addition, MSCs were efficiently infected with HTLV-1 in vitro through direct contact with HTLV-1-infected cells; however, cell-free virus particles were not capable of causing infection. In summary, HTLV-1 can alter MSC function, and this mechanism may contribute to the pathogenesis of this viral infection.
Asunto(s)
Infecciones por HTLV-I/virología , Virus Linfotrópico T Tipo 1 Humano/fisiología , Células Madre Mesenquimatosas/virología , Diferenciación Celular , Células Cultivadas , Infecciones por HTLV-I/genética , Infecciones por HTLV-I/inmunología , Infecciones por HTLV-I/fisiopatología , Humanos , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/inmunología , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/inmunología , Fenotipo , Molécula 1 de Adhesión Celular Vascular/genética , Molécula 1 de Adhesión Celular Vascular/inmunologíaRESUMEN
Human T cell leukemia virus type 1 (HTLV-1) preferentially infects CD4(+) T cells and these cells play a central role in HTLV-1 infection. In this study, we investigated the global gene expression profile of circulating CD4(+) T cells from the distinct clinical status of HTLV-1-infected individuals in regard to TAX expression levels. CD4(+) T cells were isolated from asymptomatic HTLV-1 carrier (HAC) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients in order to identify genes involved in HAM/TSP development using a microarray technique. Hierarchical clustering analysis showed that healthy control (CT) and HTLV-1-infected samples clustered separately. We also observed that the HAC and HAM/TSP groups clustered separately regardless of TAX expression. The gene expression profile of CD4(+) T cells was compared among the CT, HAC, and HAM/TSP groups. The paxillin (Pxn), chemokine (C-X-C motif ) receptor 4 (Cxcr4), interleukin 27 (IL27), and granzyme A (Gzma) genes were differentially expressed between the HAC and HAM/TSP groups, regardless of TAX expression. The perforin 1 (Prf1) and forkhead box P3 (Foxp3) genes were increased in the HAM/TSP group and presented a positive correlation to the expression of TAX and the proviral load (PVL). The frequency of CD4(+)FOXP3(+) regulatory T cells (Treg) was higher in HTLV-1-infected individuals. Foxp3 gene expression was positively correlated with cell lysis-related genes (Gzma, Gzmb, and Prf1). These findings suggest that CD4(+) T cell activity is distinct between the HAC and HAM/TSP groups.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/virología , Portador Sano/inmunología , Genes pX , Infecciones por HTLV-I/inmunología , Adulto , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The seroprevalence and geographic distribution of HTLV-1/2 among blood donors are extremely important to transfusion services. We evaluated the seroprevalence of HTLV-1/2 infection among first-time blood donor candidates in Ribeirão Preto city and region. From January 2000 to December 2010, 1,038,489 blood donations were obtained and 301,470 were first-time blood donations. All samples were screened with serological tests for HTLV-1/2 using enzyme immunoassay (EIA). In addition, the frequency of coinfection with hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), Chagas disease (CD) and syphilis was also determined. In-house PCR was used as confirmatory test for HTLV-1/2. A total of 296 (0.1%) first-time donors were serologically reactive for HTLV-1/2. Confirmatory PCR of 63 samples showed that 28 were HTLV-1 positive, 13 HTLV-2 positive, 19 negative and three indeterminate. Regarding HTLV coinfection rates, the most prevalent was with HBV (51.3%) and HCV (35.9%), but coinfection with HIV, CD and syphilis was also detected. The real number of HTLV-infected individual and coinfection rate in the population is underestimated and epidemiological studies like ours are very informative.
A soroprevalência e a distribuição geográfica do HTLV-1/2 entre os doadores de sangue são extremamente importantes para os serviços de transfusão. Neste trabalho, foi determinada a soroprevalência da infecção pelo HTLV-1/2 entre os doadores de sangue de primeira vez da cidade de Ribeirão Preto e região. No período de Janeiro de 2000 a Dezembro de 2010, 1.038.489 doações de sangue foram obtidas sendo 301.470 doações de primeira vez. Todas as amostras foram avaliadas com testes sorológicos para HTLV-1/2 usando ensaio imunoenzimático (EIA). Adicionalmente, a frequência de coinfecção com o vírus da hepatite B (HBV), vírus da hepatite C (HCV), vírus da imunodeficiência humana (HIV), doença de Chagas (CD) e sífilis também foi determinada. Adicionalmente, foi utilizada uma reação de PCR in-house como teste confirmatório para HTLV-1/2. Um total de 296 (0,1%) doadores de primeira vez foram sorologicamente reativos para HTLV-1/2. O PCR confirmatório de 63 amostras mostrou que 28 eram HTLV-1 positivas, 13 HTLV-2 positivas, 19 negativas e três indeterminadas. Em relação às taxas de coinfecção com HTLV1/2, a maior prevalência foi com HBV (51,3%) e HCV (35,9%), mas a coinfecção com HIV, CD e sífilis também foram detectadas. O número real de indivíduos infectados pelo HTLV-1 e a taxa de coinfecção na população é subestimado e estudos epidemiológicos como esse são muito informativos.
Asunto(s)
Adolescente , Adulto , Humanos , Persona de Mediana Edad , Adulto Joven , Donantes de Sangre/estadística & datos numéricos , Coinfección/epidemiología , Infecciones por HTLV-I/epidemiología , Infecciones por HTLV-II/epidemiología , Brasil/epidemiología , Coinfección/diagnóstico , Infecciones por HTLV-I/diagnóstico , Infecciones por HTLV-II/diagnóstico , Virus Linfotrópico T Tipo 1 Humano/genética , Virus Linfotrópico T Tipo 1 Humano/inmunología , /genética , /inmunología , Técnicas para Inmunoenzimas , Reacción en Cadena de la Polimerasa , Estudios SeroepidemiológicosRESUMEN
The seroprevalence and geographic distribution of HTLV-1/2 among blood donors are extremely important to transfusion services. We evaluated the seroprevalence of HTLV-1/2 infection among first-time blood donor candidates in Ribeirão Preto city and region. From January 2000 to December 2010, 1,038,489 blood donations were obtained and 301,470 were first-time blood donations. All samples were screened with serological tests for HTLV-1/2 using enzyme immunoassay (EIA). In addition, the frequency of coinfection with hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), Chagas disease (CD) and syphilis was also determined. In-house PCR was used as confirmatory test for HTLV-1/2. A total of 296 (0.1%) first-time donors were serologically reactive for HTLV-1/2. Confirmatory PCR of 63 samples showed that 28 were HTLV-1 positive, 13 HTLV-2 positive, 19 negative and three indeterminate. Regarding HTLV coinfection rates, the most prevalent was with HBV (51.3%) and HCV (35.9%), but coinfection with HIV, CD and syphilis was also detected. The real number of HTLV-infected individual and coinfection rate in the population is underestimated and epidemiological studies like ours are very informative.
Asunto(s)
Donantes de Sangre/estadística & datos numéricos , Coinfección/epidemiología , Infecciones por HTLV-I/epidemiología , Infecciones por HTLV-II/epidemiología , Adolescente , Adulto , Brasil/epidemiología , Coinfección/diagnóstico , Infecciones por HTLV-I/diagnóstico , Infecciones por HTLV-II/diagnóstico , Virus Linfotrópico T Tipo 1 Humano/genética , Virus Linfotrópico T Tipo 1 Humano/inmunología , Virus Linfotrópico T Tipo 2 Humano/genética , Virus Linfotrópico T Tipo 2 Humano/inmunología , Humanos , Técnicas para Inmunoenzimas , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Estudios Seroepidemiológicos , Adulto JovenRESUMEN
Leukotrienes (LTs) are lipid mediators involved in several inflammatory disorders. We investigated the LT pathway in human T-lymphotropic virus type 1 (HTLV-1) infection by evaluating LT levels in HTLV-1-infected patients classified according to the clinical status as asymptomatic carriers (HACs) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients. Bioactive LTB(4) and CysLTs were both increased in the plasma and in the supernatant of peripheral blood mononuclear cell cultures of HTLV-1-infected when compared to non-infected. Interestingly, CysLT concentrations were increased in HAM/TSP patients. Also, the concentration of plasma LTB(4) and LTC(4) positively correlated with the HTLV-1 proviral load in HTLV-1-infected individuals. The gene expression levels of LT receptors were differentially modulated in CD4(+) and CD8(+) T cells of HTLV-1-infected patients. Analysis of the overall plasma signature of immune mediators demonstrated that LT and chemokine amounts were elevated during HTLV-1 infection. Importantly, in addition to CysLTs, IP-10 was also identified as a biomarker for HAM/TSP activity. These data suggest that LTs are likely to be associated with HTLV-1 infection and HAM/TSP development, suggesting their putative use for clinical monitoring.