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1.
Rev. cuba. pediatr ; 91(1): e441, ene.-mar. 2019. tab, graf
Artigo em Espanhol | LILACS (Américas) | ID: biblio-985592

RESUMO

Introducción: Existen pocas investigaciones sobre factores de riesgo de tumores renales pediátricos. Objetivo: Caracterizar en detalle regiones geográficas de alta incidencia de tumores renales pediátricos en el centro de Argentina y su posible vinculación con factores de riesgo genéticos. Métodos: El área de estudio comprendió la provincia de Córdoba (Argentina). Se generó una base de datos de incidencia del cáncer renal infantil con información del Registro Provincial de Tumores. Se realizaron análisis de conglomerados espaciotemporales. En localidades dentro de los conglomerados, se llevaron a cabo entrevistas en profundidad a informantes claves. Resultados: Se registraron 56 casos de tumores renales pediátricos en el Registro en el periodo 2004-2013. Se detectó un conglomerado espacial significativo que abarca siete departamentos de la provincia. En esa región se concretaron seis entrevistas en profundidad a informantes claves. Los entrevistados resaltaron la mayor frecuencia de enfermedad genética de Sandhoff y las prácticas de endogamia (corroboradas en numerosos resultados científicos). A partir de estos datos se determinaron zonas de superposición de tumores renales y de la enfermedad de Sandhoff. Conclusiones: Se detectó una región particular de la provincia con alta frecuencia de tumores renales pediátricos y de la enfermedad de Sandhoff. Numerosos estudios científicos determinan que la endogamia es el factor de riesgo que aumenta la frecuencia de esta enfermedad en esta región. En futuras investigaciones se deberá corroborar si la endogamia también actúa aumentando la incidencia de tumores renales infantiles(AU)


Introduction: There is little research on risk factors of pediatric renal tumors. Objective: To characterize in detail the geographic regions of greatest incidence of pediatric renal tumors in central Argentina and exploring their possible link to genetic risk factors. Methods: The study area comprised the province of Córdoba (Argentina), and a database of pediatric renal tumors incidence was generated with information from the Provincial Tumor Registry. Analyses of spatio-temporal clusters were performed. In-depth interviews with key informants were carried out at localities within the conglomerates. Results: 56 cases of pediatric renal tumors were registered in the Provincial Registry of Tumors between 2004 and 2013. A significant spatial conglomerate was detected, covering seven districts of the province. In that region, six in-depth interviews were conducted with key informants. Interviewees highlighted the increased frequency of Sandhoff genetic disease and endogamous practices (corroborated in numerous scientific results). From these data, zones of overlap of renal tumors and of Sandhoff disease were determined. Conclusions: A particular region of the province was detected with high frequency of pediatric renal tumors and Sandhoff disease. Numerous scientific studies have determined that endogamy is the risk factor that increases the frequency of Sandhoff disease in this region. In future research, it should be confirmed whether it also acts by increasing the incidence of renal tumors in children(AU)


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Consanguinidade , Predisposição Genética para Doença/etiologia , Neoplasias Renais/complicações , Neoplasias Renais/epidemiologia , Argentina , Conglomerados Espaço-Temporais , Neoplasias Renais/genética
2.
J. bras. nefrol ; 37(2): 248-254, Apr-Jun/2015. tab, graf
Artigo em Português | LILACS (Américas) | ID: lil-751455

RESUMO

Resumo Introdução O câncer renal é uma doença oncourológica complexa e multifatorial. Objetivo: Realizar uma meta-análise para investigar a associação do polimorfismo nulo dos genes GSTM1 e GSTT1 no contexto do câncer renal. Método: Estudos em seres humanos, do tipo caso-controle, publicados no período de 1999 a 2013, que investigavam a associação do polimorfismo nulo dos genes GSTM1 e GSTT1 no câncer renal, foram agrupados para a confecção da presente meta-análise. Resultados: Foram selecionados 10 artigos sobre o tema proposto. Não foram encontradas associações entre o polimorfismo nulo dos genes GSTM1 (OR = 1,015; IC95% = 0,897-1,147) e GSTT1 (OR = 1,081; IC95% = 0,791- 1,479) e o câncer renal. Conclusões: Conclui-se que os polimorfismos nulos de GSTM1 e GSTT1 não estão associados ao risco do desenvolvimento de câncer renal, pois apresentam papel limitado, se é que existe alguma contribuição efetiva, no desenvolvimento dos tumores renais. .


Abstract Introduction: Renal cancer is a complex and multifactorial oncourologic disease. Objective: To conduct a meta-analysis in order to investigate the association of GSTM1 and GSTT1 genes null polymorphisms in renal cancer. Method: Case-control studies in humans, published from 1999 to 2013, that investigated the association of GSTM1 and GSTT1 genes null polymorphisms in renal cancer were grouped in order to make of this meta-analysis. Results: Ten articles were selected on the subject proposed. No associations were found between polymorphisms of GSTM1-null (OR = 1.015, 95% CI = 0.897 to 1.147) and GSTT1-null (OR = 1.081, 95% CI = 0.791 to 1.479) and renal cancer. Conclusions: Based on the results obtained, we conclude that the GSTM1 and GSTT1 null polymorphisms are not associated with the risk of developing renal cancer, since they have limited role, if there is any on effective contribution in the development of renal tumors. .


Assuntos
Humanos , Predisposição Genética para Doença , Glutationa Transferase/genética , Neoplasias Renais/genética , Polimorfismo Genético
3.
Rev. bras. parasitol. vet ; 23(4): 509-515, Oct-Dec/2014. tab, graf
Artigo em Inglês | LILACS (Américas) | ID: lil-731257

RESUMO

Different parasites that commonly occur concomitantly can influence one another, sometimes with unpredictable effects. We evaluated pathological aspects of dogs naturally co-infected with Leishmania infantum and Ehrlichia canis. The health status of the dogs was investigated based on histopathological, hematological and biochemical analyses of 21 animals infected solely with L. infantum and 22 dogs co- infected with L. infantum and E. canis. The skin of both groups showed chronic, predominantly lymphohistioplasmacytic inflammatory reaction. The plasmacytosis in the lymphoid tissues was likely related with the hypergammaglobulinemia detected in all the dogs. The disorganization of extracellular matrix found in the reticular dermis of the inguinal region and ear, characterized by the substitution of thick collagen fibers for thin fibers, was attributed to the degree of inflammatory reaction, irrespective of the presence of parasites. In addition, the histopathological analysis revealed that twice as many dogs in the co-infected group presented Leishmania amastigotes in the ear skin than those infected solely with Leishmania, increasing the possibility of becoming infected through sand fly vectors. Our findings highlight the fact that the health of dogs infected concomitantly with L. infantum and E. canis is severely compromised due to their high levels of total plasma protein, globulins, alkaline phosphatase and creatine kinase, and severe anemia.


A infecção simultânea por parasitas de diferentes espécies pode resultar em alterações imprevisíveis. O presente estudo avaliou a patologia de cães naturalmente coinfectados por Leishmania infantum e Ehrlichia canis. A saúde dos cães foi investigada pelas análises histopatológicas, hematológicas e bioquímicas de 21 cães infectados somente por L. infantum e 22 cães coinfectados por L. infantum e E. canis. Observou-se uma reação inflamatória crônica, predominantemente linfohistioplasmocítica, na pele dos dois grupos. A plasmocitose, encontrada nos tecidos linfóides, provavelmente estava relacionada com a hipergamaglobulinemia observada em todos os cães amostrados. A desorganização da matriz extracelular da derme da região inguinal e da orelha, demonstrada pela substituição das fibras de colágeno espessas por fibras finas, foi relacionada com o grau de reação inflamatória, independente da presença de parasitas. Ainda, observamos duas vezes mais animais do grupo coinfectado apresentando formas amastigotas na pele de orelha pela histopatologia comparado ao número de cães infectados apenas por Leishmania, tornando-os desta forma mais infectivos aos vetores. Nossos resultados ressaltam que a saúde de cães coinfectados estava severamente comprometida devido aos altos níveis de proteína plasmática total, globulinas, fosfatase alcalina, creatina quinase e anemia acentuada.


Assuntos
Humanos , Ciclina D1/genética , Genes Supressores de Tumor , Ligases/genética , Proteínas Supressoras de Tumor , Ubiquitina-Proteína Ligases , Doença de von Hippel-Lindau/genética , Northern Blotting , Carcinoma de Células Renais/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , Análise de Sequência com Séries de Oligonucleotídeos , Oxigênio/farmacologia , Transfecção , Células Tumorais Cultivadas , Proteína Supressora de Tumor Von Hippel-Lindau
4.
An. bras. dermatol ; 88(6,supl.1): 124-127, Nov-Dec/2013. graf
Artigo em Inglês | LILACS (Américas) | ID: lil-696802

RESUMO

A 34-year-old woman with no known medical history was evaluated for multiple painful brown nodules and papules on the anterior aspect of the trunk. She mentioned a history of similar cutaneous findings on her mother. Biopsies of three lesions revealed piloleiomyomata. Renal and adrenal ultrasound revealed an isolated simple cortical cyst, and pelvic and endovaginal ultrasound revealed two uterine myomata. The clinical diagnosis of hereditary leiomyomatosis and renal cell cancer was corroborated by the identification of a heterozygous variant on exon 5 of the fumarate hydratase gene (c.578C>T p.T193I). Identification of the tumor piloleiomyoma should alert the dermatologist to this rare genodermatosis, which is associated with an increased risk of renal cell tumors, demanding multidisciplinary follow-up, and personal and family counseling.


Uma mulher de 34 anos sem antecedentes patológicos conhecidos foi avaliada por apresentar múltiplos nódulos e pápulas castanhos, dolorosos, na face anterior do tronco. Referia história de achados cutâneos semelhantes na sua mãe. As biópsias de três lesões revelaram piloleiomiomas. As ecografias renal e suprarenal identificaram apenas cisto renal cortical simples, e as ecografias endovaginal e pélvica, dois miomas uterinos. O diagnóstico clínico de leiomiomatose herediária e câncer de células renais foi corroborado pela identificação de variante heterozigota no exon 5 do gene da Fumarato hidratase (c.578C>T p.T193I). O piloleimomioma é um tumor cuja identificação deve alertar o dermatologista para esta rara genodermatose, associada a um risco aumentado de tumores de células renais, exigindo seguimento multidisciplinar e aconselhamento pessoal e familiar.


Assuntos
Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Leiomiomatose/patologia , Neoplasias Cutâneas/patologia , Pele/patologia , Neoplasias Uterinas/patologia , Biópsia , Carcinoma de Células Renais/genética , Fumarato Hidratase/genética , Predisposição Genética para Doença , Neoplasias Renais/genética , Leiomiomatose/genética , Neoplasias Cutâneas/genética , Neoplasias Uterinas/genética
5.
Rev. Col. Bras. Cir ; 40(6): 471-475, nov.-dez. 2013. ilus, graf, tab
Artigo em Português | LILACS (Américas) | ID: lil-702656

RESUMO

OBJETIVO: avaliar a frequência de deleção do gene PTEN no carcinoma de células renais e o impacto da deleção nas taxas de sobrevida global e livre de doença. MÉTODOS: foram analisados 110 pacientes portadores de carcinoma de células renais submetidos à nefrectomia radical ou parcial entre os anos de 1980 e 2007. Em 53 casos foi possível a análise do gene PTEN pelo método de hibridização in situ fluorescente através da técnica de "tissue microarray". Para a análise estatística, os pacientes foram classificados em dois grupos, de acordo com a presença ou ausência de deleção. RESULTADOS: o tempo médio de seguimento foi de 41,9 meses. Deleção hemizigótica foi identificada em 18 pacientes (33,9%), ao passo que deleção homozigótica esteve presente em três (5,6%). Em aproximadamente 40% dos casos analisados havia deleção. Monossomia e trissomia foram detectadas, respectivamente, em nove (17%) e dois pacientes (3,8%). Em 21 pacientes (39,6%), a análise por hibridização in situ do gene PTEN foi normal. Não houve diferenças estatisticamente significativas nas taxas de sobrevida global (p=0,468) e livre de doença (p=0,344) entre os pacientes portadores ou não de deleção. Foram fatores independentes para a sobrevida global: estádio clínico TNM, sintomatologia ao diagnóstico, alto grau de Fuhrmann performance status (Ecog) e recorrência tumoral. A livre de doença foi influenciada unicamente pelo estádio clínico TNM. CONCLUSÃO: deleção do gene PTEN no CCR foi detectada com frequência de aproximadamente 40% e sua presença não foi determinante de menores taxas de sobrevida, permanecendo os fatores prognósticos tradicionais como determinantes da evolução dos pacientes.


OBJECTIVE: To evaluate the frequency of deletion of the PTEN gene in renal cell carcinoma (RCC) and its impact on the rates of overall and disease-free survival. METHODS: We analyzed 110 patients with renal cell carcinoma who underwent radical or partial nephrectomy between 1980 and 2007. In 53 cases it was possible to analyse the PTEN gene by the method of fluorescent in situ hybridization using the technique of tissue microarray. For statistical analysis, patients were classified in two groups according to the presence or absence of the deletion. RESULTS: The mean follow-up time was 41.9 months. Hemizygous deletion was detected in 18 patients (33.9%), while the homozygous one was present in three (5.6%). Deletion was present in approximately 40% of the analyzed cases. Monosomy and trisomy were detected in nine (17%) and two patients (3.8%), respectively. In 21 patients (39.6%) the analysis of the PTEN gene by in situ hybridization was normal. There were no statistically significant differences in overall (p = 0.468) and disease-free (p = 0.344) survival rates between patients with or without deletion. Factors which were independent for overall survival: TNM clinical stage, symptoms at diagnosis, high Fuhrmann grade, performance status (ECoG) and tumor recurrence. Disease-free survival was influenced only by the clinical TNM stage. CONCLUSION: Deletion of the PTEN gene in RCC was detected with a frequency of approximately 40% and its presence was not determinant of lower survival rates, the traditional prognostic factors remaining as determinants of outcome.


Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Renais/genética , Deleção de Genes , Neoplasias Renais/genética , PTEN Fosfo-Hidrolase/genética , Carcinoma de Células Renais/mortalidade , Intervalo Livre de Doença , Hibridização in Situ Fluorescente , Neoplasias Renais/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida , Análise Serial de Tecidos
6.
Clinics ; 68(6): 825-833, jun. 2013. graf
Artigo em Inglês | LILACS (Américas) | ID: lil-676926

RESUMO

OBJECTIVES: MiRNAs are intrinsic RNAs that interfere with protein translation. Few studies on the synergistic effects of miRNAs have been reported. Both miR-424 and miR-381 have been individually reported to be involved in carcinogenesis. They share a common putative target, WEE1, which is described as an inhibitor of G2/M progression. Here, we studied the synergistic effects of miR-424 and miR-381 on renal cancer cells. METHODS: The viability of 786-O cells was analyzed after transfection with either a combination of miR-424 and miR-381 or each miRNA alone. We investigated cell cycle progression and apoptosis with flow cytometry. To confirm apoptosis and the abrogation of G2/M arrest, we determined the level of pHH3, which is an indicator of mitosis, and caspase-3/7 activity. The expression levels of WEE1, Cdc25, γH2AX, and Cdc2 were manipulated to investigate the roles of these proteins in the miRNA-induced anti-tumor effects. To verify that WEE1 was a direct target of both miR-424 and miR-381, we performed a dual luciferase reporter assay. RESULTS: We showed that the combination of these miRNAs synergistically inhibited proliferation, abrogated G2/M arrest, and induced apoptosis. This combination led to Cdc2 activation through WEE1 inhibition. This regulation was more effective when cells were treated with both miRNAs than with either miRNA alone, indicating synergy between these miRNAs. WEE1 was verified to be a direct target of each miRNA according to the luciferase reporter assay. CONCLUSIONS: These data clearly demonstrate that these two miRNAs might synergistically act as novel modulators of tumorigenesis by down-regulating WEE1 expression in renal cell cancer cells. .


Assuntos
Humanos , Carcinoma de Células Renais/genética , Proteínas de Ciclo Celular/metabolismo , Ciclina B/metabolismo , Neoplasias Renais/genética , MicroRNAs/farmacologia , Proteínas Nucleares/metabolismo , Proteínas Tirosina Quinases/metabolismo , Western Blotting , Linhagem Celular Tumoral , Fenômenos Fisiológicos Celulares , Transformação Celular Neoplásica , Regulação para Baixo , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Tempo , Regulação para Cima
7.
Int. braz. j. urol ; 36(4): 410-419, July-Aug. 2010. graf, tab
Artigo em Inglês | LILACS (Américas) | ID: lil-562107

RESUMO

PURPOSE: The determination of prognosis in patients with renal cell carcinoma (RCC) is based, classically, on stage and histopathological aspects. The metastatic disease develops in one third of patients after surgery, even in localized tumors. There are few options for treating those patients, and even the new target designed drugs have shown low rates of success in controlling disease progression. Few studies used high throughput genomic analysis in renal cell carcinoma for determination of prognosis. This study is focused on the identification of gene expression signatures in tissues of low-risk, high-risk and metastatic RCC clear cell type (RCC-CCT). MATERIALS AND METHODS: We analyzed the expression of approximately 55,000 distinct transcripts using the Whole Genome microarray platform hybridized with RNA extracted from 19 patients submitted to surgery to treat RCC-CCT with different clinical outcomes. They were divided into three groups (1) low risk, characterized by pT1, Fuhrman grade 1 or 2, no microvascular invasion RCC; (2) high risk, pT2-3, Fuhrman grade 3 or 4 with, necrosis and microvascular invasion present and (3) metastatic RCC-CCT. Normal renal tissue was used as control. RESULTS: After comparison of differentially expressed genes among low-risk, high-risk and metastatic groups, we identified a group of common genes characterizing metastatic disease. Among them Interleukin-8 and Heat shock protein 70 were over-expressed in metastasis and validated by real-time polymerase chain reaction. CONCLUSION: These findings can be used as a starting point to generate molecular markers of RCC-CCT as well as a target for the development of innovative therapies.


Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Renais/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Renais/genética , Carcinoma de Células Renais/patologia , Progressão da Doença , Proteínas de Choque Térmico , Neoplasias Renais/patologia , Análise em Microsséries , Estadiamento de Neoplasias , Biomarcadores Tumorais/genética
8.
IBJ-Iranian Biomedical Journal. 2010; 14 (3): 77-82
em Inglês | IMEMR (Mediterrâneo Oriental) | ID: emr-108581

RESUMO

The ectopic expression of receptor tyrosine kinase Rorl has been reported in patients with hematological malignancies such as chronic lymphocytic leukemia and acute lymphoblastic leukemia. Here we report, for the first time, expression of ROR1 gene in both tumor tissues and peripheral blood mononuclear cells [PBMC] from patients with renal cancer [RC]. In the current study, the expression of ROR1 gene was semi-quantitatively measured in PBMC and tumor tissues from 16 RC patients as well as PBMC from 22 healthy individuals relative to the expression of the housekeeping gene phosphoglucomutase 1 by RT-PCR. Our results showed that ROR1 was expressed at gene level in 81.3% of renal tumor tissues [13 out of 16] whereas it was expressed in 94% of PBMC from RC patients [15 out of 16]. A weak expression of RORl was observed in PBMC of 4 out of 22 healthy individual. A significant expression of ROR1 was observed in PBMC from RC patients when compared to that in PBMC from normal healthy individuals [P<0.001]. The expression of ROR1 in PBMC may reflect a shedding of tumor cells into blood stream. We conclude that detection of a high level of ROR1 expression in blood cells might assist in early detection of renal malignancies, providing taking into consideration the clinical symptoms of the disease


Assuntos
Humanos , Masculino , Feminino , Neoplasias Renais/genética , Marcadores Genéticos , Biomarcadores Tumorais , Expressão Gênica , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Detecção Precoce de Câncer
9.
Arq. bras. endocrinol. metab ; 52(8): 1236-1243, Nov. 2008. ilus, tab
Artigo em Inglês | LILACS (Américas) | ID: lil-503288

RESUMO

AIM: To present phenotypic variability of WT1-related disorders. METHODS: Description of clinical and genetic features of five 46,XY patients with WT1 anomalies. RESULTS: Patient 1: newborn with genital ambiguity; he developed Wilms tumor (WT) and chronic renal disease and died at the age of 10 months; the heterozygous 1186G>A mutation compatible with Denys-Drash syndrome was detected in this child. Patients 2 and 3: adolescents with chronic renal disease, primary amenorrhea and hypergonadotrophic hypogonadism; patient 2 had a gonadoblastoma. The heterozygous IVS9+4, C>T mutation, compatible with Frasier syndrome was detected. Patient 4: 9-year-old boy with aniridia, genital ambiguity, dysmorphisms and mental deficiency; a heterozygous 11p deletion, compatible with WAGR syndrome was detected. Patient 5: 2 months old, same diagnosis of patient 4; he developed WT at the age of 8 months. CONCLUSIONS: Constitutional abnormalities of WT1 cause gonadal and renal anomalies and predisposition to neoplasia and must be investigated in patients with ambiguous genitalia, chronic renal disease and(or) Wilms tumors; primary amenorrhea with chronic renal disease; and aniridia, genital ambiguity and dysmorphisms.


OBJETIVO: Descrever a variabilidade fenotípica das anomalias relacionadas ao WT1. MÉTODOS: Descrição das características clínicas e genéticas de cinco pacientes 46,XY com anomalias no WT1. RESULTADOS: Paciente 1: Recém-nascido com ambigüidade genital desenvolveu tumor de Wilms (TW) e insuficiência renal crônica (IRC), com óbito aos 10 meses. Detectada a mutação 1186G>A em heterozigose, compatível com síndrome de Denys-Drash. Pacientes 2 e 3: Adolescentes com IRC, amenorréia primária e hipogonadismo hipergonadotrófico; a paciente 2 apresentava gonadoblastoma. Ambas apresentavam mutação IVS9+4, C>T em heterozigose, característica da síndrome de Frasier. Paciente 4: Idade 9 anos, aniridia, ambigüidade genital, dismorfismos e deficiência mental; deleção 11p, compatível com síndrome WAGR foi encontrada em heterozigose. Paciente 5: Dois meses, mesmo diagnóstico do paciente 4, desenvolveu TW aos 8 meses. CONCLUSÕES: Alterações constitucionais do WT1 determinam anomalias gonadais, renais e predisposição a neoplasias; devem ser pesquisadas em casos de ambigüidade genital associada a IRC e(ou) TW; de amenorréia primária com IRC; e aniridia, ambigüidade genital e dismorfismos.


Assuntos
Adolescente , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Síndrome de Frasier , Genes do Tumor de Wilms , Neoplasias Renais , Proteínas WT1/genética , Amenorreia/diagnóstico , Evolução Fatal , Síndrome de Frasier/diagnóstico , Síndrome de Frasier/genética , Genitália/anormalidades , Genitália/patologia , Heterozigoto , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Fenótipo , Insuficiência Renal Crônica/diagnóstico
10.
Int. braz. j. urol ; 34(4): 492-502, July-Aug. 2008. ilus, graf
Artigo em Inglês | LILACS (Américas) | ID: lil-493670

RESUMO

PURPOSE: Renal cell carcinoma (RCC) is the most lethal among the common urologic malignancies, comprising 3 percent of all human neoplasias; approximately 40 percent of patients eventually die of cancer progression. One third of patients who present with metastatic disease and up to 40 percent treated for localized disease generally experience recurrence. RCCs are characterized by high resistance to chemo-, radio- and immunotherapy. We recently discovered an endogenous enzymatic activity, which is particularly expressed in tumorigenic cell, endogenous non-telomerase reverse transcriptase (RT) of retrotrasposon / retroviral origin, as a specific target to induce proliferation arrest in a number of human carcinogenesis in vitro culture cell lines. METHODS: To address this possibility, we have employed RCC primary cell culture testing pharmacological inhibition, in vitro, by two characterized non nucleosidic RT inhibitors, nevirapine and efavirenz; next, we assessed morphological effects and analyzed putative modulation on gene expression profile. RESULTS: Both treatments reduced cell proliferation rate and induced morphological differentiation and gene expression reprogramming in different RCC analyzed tumor biomarkers. CONCLUSION: In this study we describe a new potential therapeutic approach to obtain considerable future benefits in renal carcinoma cure and attempt to establish a new possible pharmacological therapy based on oral drugs administration in renal RCC treatment.


Assuntos
Humanos , Antineoplásicos/uso terapêutico , Benzoxazinas/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Nevirapina/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , RNA , Células Tumorais Cultivadas
12.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-173543

RESUMO

Birt-Hogg-Dube syndrome (BHDS) is an autosomal dominant genodermatosis characterized by cutaneous hair follicle tumors (fibrofolliculoma or trichodiscoma), pulmonary cysts, and increased risk of renal neoplasia. The genetic alteration for BHDS has been mapped to chromosome 17p12q11, and the gene in this region has been cloned and believed to be responsible for the BHDS. Mutations in the BHD gene (also known as FLCN) have been described in the patients with BHDS. We present a case of a 30-yr-old Korean woman with multiple mildly pruritic papules on her face and neck area. The patient had several firm, flesh-colored, dome-shaped, papular lesions measuring between 2 to 5 mm. Except for a history of pneumothorax her medical records were not remarkable. Mutation analysis of the BHD gene was performed, and a novel deletion mutation (p.F519LfsX17 [c.1557delT]) causing truncation of the gene product, folliculin, was found in the exon 14. The actual incidence of BHDS is unknown, but it is most likely underdiagnosed. So it is imperative that doctors recognize the skin lesions of BHDS and institute proper screening to detect other manifestations of the disease. Here, we report a case of BHDS with a novel mutation, which is the first report in Korea.


Assuntos
Adulto , Biópsia , Análise Mutacional de DNA , Diagnóstico Diferencial , Estrona/biossíntese , Éxons , Feminino , Deleção de Genes , Predisposição Genética para Doença , Humanos , Neoplasias Renais/genética , Modelos Genéticos , Mutação , Dermatopatias/diagnóstico , Síndrome
14.
Int. braz. j. urol ; 33(5): 622-629, Sept.-Oct. 2007. ilus, tab
Artigo em Inglês | LILACS (Américas) | ID: lil-470212

RESUMO

OBJECTIVE: Investigate the possible association of insertion/deletion (2G/G) polymorphism at nucleotide -1607 of the MMP-1 promoter with the development and progression of renal cancer MATERIALS AND METHODS: In this study, we genotyped 217 individuals, 99 patients with renal cell carcinoma (RCC) and 118 controls without cancer. DNA specimens were extracted from epithelial buccal cells and paraffin-embedded tissue of RCC patients and from epithelial buccal cells and blood cells of healthy controls RESULTS: The difference in frequency of 2G/2G genotype between controls (22.9 percent) and RCC patients (28.6 percent) was not statistically significant (p = 0.461). We also did not find correlation between 2G/2G and histological type of RCC. The comparison of genotype distribution and frequency of 2G allele in different populations showed a strong variability of 2G allele frequency among the different ethnic groups. This fact may influence on the collaboration of this 2G allele in RCC or others diseases CONCLUSION: Our data suggest that the matrix metalloproteinase-1 (MMP-1) promoter polymorphism may not play a significant role in renal cell carcinoma patients in Brazil.


Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Metaloproteinase 1 da Matriz/genética , Regiões Promotoras Genéticas , Polimorfismo de Nucleotídeo Único/genética , Estudos de Casos e Controles , Carcinoma de Células Renais/enzimologia , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Neoplasias Renais/enzimologia , Polimorfismo de Fragmento de Restrição
16.
Int. braz. j. urol ; 31(3): 251-255, May-June 2005.
Artigo em Inglês | LILACS (Américas) | ID: lil-411100

RESUMO

We report the case of a 58-year old patient, showing a solid image in the right kidney, who underwent radical nephrectomy that revealed neoplasia, whose pathological study led to the diagnosis of kidney carcinoma associated with Xp11.2 translocation / TFE3 (ASPL-TFE3) gene fusion. The authors discuss aspects related to this lesion, such as frequency, pathogenesis, clinical presentation, histopathology and outcome, as observed in the literature.


Assuntos
Feminino , Humanos , Pessoa de Meia-Idade , Carcinoma de Células Renais/genética , Cromossomos Humanos X/genética , Proteínas de Ligação a DNA/genética , Neoplasias Renais/genética , Fatores de Transcrição/genética , Translocação Genética/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia
17.
São Paulo; s.n; 2005. [149] p. ilus, tab, graf.
Tese em Português | LILACS (Américas) | ID: lil-424885

RESUMO

O carcinoma de células renais (CCR) é uma causa crescente de morte por câncer. Melhor entendimento da biologia tumoral pode levar a terapias mais eficientes. Estudou-se a sinalização celular originada de EGFR em CCR e o efeito de um inibidor de EGFR (gefitinibe), um inibidor de MAPK (UO126) e um inibidor de mTOR (rapamicina) na fosforilação de intermediários da via de MAPK, em componentes do complexo de início de tradução (CIT) e no crescimento de culturas celulares. UO126 promoveu defosforilação de substratos de mTOR revelando comunicação entre MAPK e CIT. Gefitinibe bloqueou a sinalização entre EGFR e as vias PI3K e MAPK. Rapamicina foi um potente inibidor do crescimento na maioria das linhagens celulares e seu efeito foi frequentemente potencializado por UO126 ou gefitinibe. EGFR, MAPK e CIT são alvos promissores no tratamento do CCR / Summary Renal cell carcinoma (RCC) is a rising cause of cancer death. Better understanding of tumor biology may lead to more efficient therapy based on biological agents. We studied EGFR driven cell signaling in RCC as well as the effect of an EGFR inhibitor (gefitinib) a MAPK inhibitor (UO126) and a mTOR inhibitor (rapamycin) on phosphorylation of MAPK pathway intermediates, translation initiation complex (TIC) components and growth of cell cultures. UO126 caused dephosphorylation of downstream targets of mTOR revealing a cross talk between MAPK and TIC. Gefitinib blocked EGFR signaling though PI3K and MAPK pathways. Rapamycin was found to be a potent growth inhibitor in most cell lines and its effect was often potentiated by UO126 or gefitinib. EGFR, MAPK and TIC are suitable targets...


Assuntos
Humanos , Neoplasias Renais/patologia , Reação em Cadeia da Polimerase , Biossíntese de Proteínas , Western Blotting , Neoplasias Renais/genética , Sirolimo
18.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-119639

RESUMO

Interleukin (IL)-4 inhibits proliferation of several human cancer cell lines in vitro. Although IL-4 is known to regulate proliferation of lymphocytes by modulating p27KIP1 expression, the mechanism involved in the IL-4-induced growth inhibition of nonhematopoietic cancer cells has not been fully elucidated. Previously, we reported that IL-4 suppressed proliferation of human renal cell carcinoma (RCC) cell lines in vitro. Here, we show that IL-4 inhibits cell cycle progression at the G1 phase in Caki-1 cells by increasing the expression of p21WAF1 and interferon regulatory factor (IRF)-1, and decreasing the cyclin dependent kinase (CDK) 2 activity. Up-regulation of p21WAF1 and IRF-1 expression is transcriptional, but independent of p53. The levels of p21WAF1 and IRF-1 proteins were enhanced as early as 1 h after IL-4 treatment. CDK2 activity started to decline at 4 h after IL-4 treatment, and by 24 h, was ~50% of the control. Neither the protein expressions of p27KIP1 and p16INK4a, nor the phosphorylation level of pRb was changed. The importance of p21WAF1 and IRF-1 in the growth inhibition induced by IL-4 was confirmed by antisense oligonucleotide transfection. Both of p21WAF1 and IRF-1 antisense oligonucleotides prevented IL-4-mediated growth inhibition by ~30% compared to the respective sense oligonucleotides. In summary, our study indicated that p21WAF1 and IRF-1 mediate the growth inhibitory effect of IL-4 in human RCC cells.


Assuntos
CDC2-CDC28 Quinases/metabolismo , Carcinoma de Células Renais/genética , Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proteínas de Ligação a DNA/genética , Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-4/farmacologia , Neoplasias Renais/genética , Oligonucleotídeos Antissenso/genética , Fosfoproteínas/genética
19.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-127189

RESUMO

Hypermethylation of CpG island is a common mechanism for the inactivation of tumor-related genes. In the present study, we analyzed 13 genitourinary cancer cell lines for aberrant DNA methylation of 5 tumor-related genes using methylation- specific polymerase chain reaction (MSP). GSTP1 was methylated in 5 (38.5%), E-cadherin in 1 (8%), VHL in 1 (8%), and MGMT and hMLH1 in none (0%). Six out of thirteen genitourinary cancer cell lines had methylation of at least one of five genes; 5 had one gene methylated, and, 1 had two genes methylated. Methylation of these 5 genes was not detected in any of the bladder cancer cell lines. GSTP1 was methylated in all of the 3 prostate cancer cell lines. We conclude that aberrant hypermethylation may be an important mechanism for the inactivation of cancer-related genes in kidney and prostate cancer cell lines.


Assuntos
Neoplasias da Bexiga Urinária/genética , Caderinas/genética , Metilação de DNA , Primers do DNA , Testes Genéticos/métodos , Glutationa Transferase/genética , Humanos , Isoenzimas/genética , Neoplasias Renais/genética , Ligases/genética , Masculino , Proteínas de Neoplasias/genética , O(6)-Metilguanina-DNA Metiltransferase/genética , Reação em Cadeia da Polimerase , Neoplasias da Próstata/genética , Células Tumorais Cultivadas , Neoplasias Urogenitais/genética
20.
Bol. Asoc. Méd. P. R ; 92(4/8): 72-82, Apr.-Aug. 2000.
Artigo em Inglês | LILACS (Américas) | ID: lil-411269

RESUMO

Since the discovery of oncogenes more than 20 years ago, it has been proven that cancer is a genetically determined disease. Multiple genetic alteration occurs during the course of an illness for neoplasia to develop. Transformation of positive cell growth regulators (oncogenes) and inactivations of negative cell growth regulators (tumor suppressor genes) merge to express a malignant phenotype. These genetic alterations occur as chromosomal translocations, deletions, inversion, amplification or point mutation. The objective of this review is to introduce basic concepts of molecular biology and describe the molecular genetics and biologic clinical findings of the most important solid malignant tumors in children, namely Neuroblastoma, Wilms and Rhabdomyosarcoma. It is the oncology surgeons responsibility to learn basic molecular genetics and tumor biology to provide rational and appropriate care in the setting of multidisciplinary management. Identifications of new oncogenes will continue to be important milestones in diagnosis, early detection of tumor recurrence, and as potential targets for gene therapy. Fusion proteins generated by mutated translocations are true tumor specific antigens and potential targets for therapy. The predicament is that they are proteins needing therapeutic manipulation within the tumor cell nuclei. Technological advances in molecular and genetics will develop tools necessary to manipulate the cell nuclear DNA and target cancer cell


Assuntos
Humanos , Criança , Adolescente , Tumor de Wilms/genética , Neoplasias Renais/genética , Neuroblastoma/genética , Rabdomiossarcoma/genética , Aberrações Cromossômicas , Dano ao DNA , Biologia Molecular , Tumor de Wilms/patologia , Neoplasias Renais/patologia , Neuroblastoma/patologia , Prognóstico , Rabdomiossarcoma/patologia
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