RESUMO
Floriculture represents one of the major sources of income in the Ecuadorian Andean Region that can be carried out either in open fields as in greenhouses by using chemical compounds, growing hormones and xenobiotics. Among pesticides, ethylenbisdithiocarbamate (EBDTCs) fungicides represent the most extensively used. The aim of the study was the assessment of exposure to EBDTCs in Ecuadorian floricultural workers by the determination of the urinary excretion of the main metabolite of these compounds, ethylenethiourea (ETU). For this purpose, thirty-six floriculture workers and 7 unexposed healthy subjects were recruited for the study. Median level of ETU excretion in agricultural workers before the work shift was 3.2 micrograms/g creatinine, ranging from 0.4 to 34.5 micrograms/g creatinine. After pesticide application, urinary ETU increased to 6.2 micrograms/g creatinine (1.5-26.5) microgram/g creatinine. Urinary ETU resulted significantly higher in overall workers, taken as pre- and post-shift samples, when compared to controls (0.7, 0.4-2.1 micrograms/g creatinine, p < 0.01). According to jobs, applicators showed the highest levels of ETU excretion whereas growing, post-harvesting and maintenance workers showed similar levels of exposure. Higher level ETU excretion was observed in greenhouse compared to open field workers.
Assuntos
Agricultura , Antifúngicos/toxicidade , Etilenobis (ditiocarbamatos)/toxicidade , Exposição Ocupacional/efeitos adversos , Equador , Etilenotioureia/análise , HumanosRESUMO
SUMMARY: Karyotypic complexities associated with frequent loss or rearrangement of a number of chromosome arms, deletions, and mutations affecting the TP53 region, and molecular alterations of the INK4A gene have been reported in sporadic and/or neurofibromatosis type I (NF1)-related malignant peripheral nerve sheath tumors (MPNSTs). However, no investigations addressing possible different pathogenetic pathways in sporadic and NF1-associated MPNSTs have been reported. This lack is unexpected because, despite similar morphologic and immunophenotypic features, NF1-related cases are, by definition, associated with NF1 gene defects. Thus, we investigated the occurrence of TP53 and p16(INK4A) gene deregulation and the presence of microsatellite alterations at markers located at 17p, 17q, 9p21, 22q, 11q, 1p, or 2q loci in MPNSTs and neurofibromas either related (14 cases) or unrelated (14 cases) to NF1. Our results indicate that, in MPNSTs, p16(INK4A) inactivation almost equally affects both groups. However, TP53 mutations and loss of heterozygosity involving the TP53 locus (43% versus 9%), and p53 wild type overexpression, related or not to mdm2 overexpression (71% versus 25%), seem to mainly be restricted to sporadic MPNSTs. In NF1-associated MPNSTs, our microsatellite results are consistent with the occurrence of somatic inactivation by loss of heterozygosity of the second NF1 allele.
Assuntos
Neurofibromatose 1/genética , Neoplasias do Sistema Nervoso Periférico/genética , Proteína do Retinoblastoma/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Feminino , Genes p53/genética , Humanos , Imuno-Histoquímica , Perda de Heterozigosidade , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Biologia Molecular/métodos , Proteína do Retinoblastoma/metabolismo , Proteína Supressora de Tumor p53/metabolismoAssuntos
Carcinoma de Células Acinares/patologia , Neoplasias das Glândulas Salivares/patologia , Carcinoma de Células Acinares/genética , Carcinoma de Células Acinares/metabolismo , Transformação Celular Neoplásica , Humanos , Perda de Heterozigosidade , Repetições de Microssatélites , Mutação , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
We studied a group of patients with or without individual or family history of melanoma for the occurrence of genetic alterations at microsatellite DNA sequences, usually referred to as microsatellite instability (MSI), and loss of heterozygosity (LOH). Microsatellite analysis of 3 markers located on chromosome 9p21-22 was performed for 88 melanocytic lesions, including 27 melanomas and 35 dysplastic and 26 common nevi, from 48 patients. Three additional markers, on 11q23, 17q21 and 5q22, were investigated in 16 melanomas. Overall, microsatellite alterations of the type usually considered low-level instability at 9p21-22 were observed in 22% of melanomas and 31% of dysplastic and 23% of common nevi. LOH at the same loci was found in 15% of melanomas and 8% of dysplastic nevi but never in common nevi. Cases with a positive family history of melanoma compared to those with a negative family history showed a higher microsatellite alteration frequency (43% vs. 20%), and the same was observed in melanoma compared to non-melanoma carriers (31% vs. 16%). Our results show that (i) MSI is common in all melanocytic lesions, though with differences in the group of patients which could have clinical relevance if confirmed, whereas LOH is restricted to melanomas and dysplastic nevi; (ii) various melanocytic lesions from the same patient represent clonally distinct tumors; (iii) the phenotype suggestive of DNA repair deficiency is influenced by a family or an individual history of melanoma; (iv) the microsatellite alteration frequency correlates with patient groups ordered according to increasing melanoma risk.
Assuntos
Melanoma/genética , Repetições de Microssatélites/genética , Nevo Pigmentado/genética , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 17 , Cromossomos Humanos Par 5 , Cromossomos Humanos Par 9 , Reparo do DNA , Síndrome do Nevo Displásico/genética , Síndrome do Nevo Displásico/patologia , Humanos , Perda de Heterozigosidade , Nevo Pigmentado/patologia , Reação em Cadeia da PolimeraseRESUMO
A dedifferentiated acinic cell carcinoma (AciCC) of the right parotid gland with lymph node metastases occurred in a 36-year-old woman. The tumour was associated with a bilateral well-differentiated AciCC. The two components of this tumour had different (high and low) proliferative activity measured by Mib-1 and different (aneuploid and diploid) DNA content. Despite the presence of a high-grade component, TP53 mutations, microsatellite instability (MSI) and/or loss of heterozygosity (LOH) at the p53 locus were not detected. Although the follow-up of the patient is very short, the aggressiveness of the tumour is shown by a recurrence in the right parotid within 4 months and by the rapid development of regional metastases.
Assuntos
Aneuploidia , Carcinoma de Células Acinares/patologia , Diploide , Neoplasias Parotídeas/patologia , Adulto , Antígenos Nucleares , Carcinoma de Células Acinares/química , Carcinoma de Células Acinares/genética , Diferenciação Celular , Divisão Celular , DNA de Neoplasias/análise , Feminino , Genes p53/genética , Humanos , Técnicas Imunoenzimáticas , Antígeno Ki-67 , Perda de Heterozigosidade , Metástase Linfática , Repetições de Microssatélites/genética , Mutação , Proteínas Nucleares/análise , Neoplasias Parotídeas/química , Neoplasias Parotídeas/genética , Reação em Cadeia da PolimeraseRESUMO
AIMS AND BACKGROUND: We evaluate the possibility to use a combination of techniques such as lymphocyte stimulation and the Cell Scan Instrument for early detection of breast cancer. This method can detect differences in lymphocytes activation in the presence of absence of cancer. METHODS: The Cell Scan is a static cytometer system able to examine cellular membrane polarization. We screened 88 women with benign breast lesions, 207 women with mammary carcinoma and 325 healthy blood donors. After lymphocytes separation, each blood sample was incubated with encephalitogenic factor (EF), phytohaemagglutinin (PHA) and Breast Antigen (-BrAg) then SCM test was performed. RESULTS: Positivity was 50% among breast cancer patients, 34% among women affected by benign disease and 27% and 22% respectively among healthy female and male controls with an increase of the specific predictivity of the test during the period of ovulation. A significant difference (P < 0.0001) was observed between healthy donors and breast cancer patients. CONCLUSIONS: This results suggest that the Cell Scan test could be useful to investigate patient's immunogenicity to molecules known to be involved in tumor development and progression, such as oncogene or suppressor gene products, which could be appropriate targets for immune-derived therapeutic approaches.
Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/imunologia , Citoplasma , Ativação Linfocitária , Linfócitos , Antígenos de Neoplasias/sangue , Doadores de Sangue , Doenças Mamárias/diagnóstico , Doenças Mamárias/imunologia , Separação Celular , Feminino , Humanos , Masculino , Mucina-1 , Mucinas/sangue , Proteína Básica da Mielina/sangue , Proteínas de Neoplasias/sangue , Fito-Hemaglutininas/sangue , Valor Preditivo dos Testes , Sequências Repetitivas de Ácido Nucleico , Sensibilidade e EspecificidadeRESUMO
The aim of the present study was to investigate the in vitro mitotic response and cytokine production after allogeneic stimulation of peripheral blood mononuclear cells (PBMC) from healthy elderly subjects. Interleukin-1 (IL-1), interleukin-2 (IL-2), gamma-Interferon (gamma-IFN), and Tumor Necrosis Factor alpha (TNF-alpha) were detected in the supernatants of mixed lymphocyte cultures (MLC). The in vitro proliferative response was significantly reduced in the elderly subjects. The amount of IL-2 detected in the supernatant from cultures of cells from elderly donors was higher than for young controls, as were the production of cytokines predominantly secreted by the macrophage population (IL-1 and TNF-alpha). There was no difference in the production of gamma-IFN by cells of elderly and young subjects.