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The objective of this study is to investigate antibacterial characteristics of a thermal plasma spray system. For this purpose, copper powder was coated on a handmade atmospheric plasma spraying system made by the stainless steel 316 substrate, which is preheated at different temperatures before spraying. A number of deposition characteristics such as antibacterial characteristics, adhesion strength and hardness of coating, was investigated. All of the spray parameters are fixed except the substrate temperature. The chemical composition was analyzed by X-ray diffraction (XRD). A scanning electron microscopy (SEM) and back scattering electron microscopy (BSE) were used to show the coating microstructure, its thickness and also the powder micrograph. The energy dispersive X-ray spectroscopy (EDX) was used to analyze the coating particles. Hardness of the deposition was examined by Vickers tester (HV0.1). Its adhesion strength was declared by cross cut tester (TQC). In addition, the percentage of bactericidal coating was evidenced with Staphylococcus aurous and Escherichia coli bacteria. Study results show that as the substrates temperature increases, the number of splats in the shape of pancake increases, the greatness and percentage of the deposition porosity both decrease. The increment of the substrate temperature leads to more oxidation and makes thicker dendrites on the splat. The enhancement of the substrate temperature also enlarges thickness and efficiency of coating. The interesting results are that antibacterial properties of coatings against the Escherichia coli are more than Staphylococcus aurous bacteria. However the bactericidal percentage of the coatings against Staphylococcus aurous and Escherichia coli bacteria roughly does not change with increasing the substrate temperature. Furthermore, by increment of the substrate temperature, coatings with both high adhesion and hardness are obtained. Accordingly, the temperature of substrate can be an important parameter for progressing mechanical properties of the antiseptic deposition.
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Antibacterianos/toxicidade , Cobre/química , Escherichia coli/efeitos dos fármacos , Gases em Plasma/química , Staphylococcus aureus/efeitos dos fármacos , Temperatura , Teste de Materiais , Microscopia Eletrônica , Aço Inoxidável , Difração de Raios XRESUMO
The synchrotron radiation emitted by runaway electrons in fusion plasma provides information regarding the particle momentum and pitch-angles of the runaway electron population through the strong dependence of the synchrotron spectrum on these parameters. Information about the runaway density and its spatial distribution, as well as the time evolution of the above quantities, can also be deduced. On the other hand, control of radial electric filed and suggestion of the methods to reduce plasma turbulence are important issues in confinement process and particle transport in the tokamaks. In this work, the effects of positive limiter biasing on electrical fluctuations and hard x-ray have been investigated. For this purpose, the radial and poloidal electric fields have been measured using the Langmuir probe, and hard x-ray has been measured using the Scintillator detector. The biased electric voltage was +250âV. Also, electrical fluctuations are analyzed using wavelet transform technique in the presence of positive biasing and without it. The results show that time-frequency activity of radial electric field multiplies in the presence of positive biasing while poloidal electric filed frequency intensity decreases.
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Campos Eletromagnéticos , Síncrotrons , Raios X , Elétrons , Modelos Teóricos , Análise de OndaletasRESUMO
Plasma cooling due to hard x-ray radiation from the Runaway electrons is an important issue in tokamaks. Thus, developing effective methods to reduce the Runaway electrons and the emitted hard x-ray is also important for optimal tokamak plasma operation. In this study, we investigated the effects of external fields on hard x-ray intensity and the Magnetohydrodynamic (MHD) activity. In other words, we presented the effects of positive biased limiter and Resonant Helical Field (RHF) on the MHD fluctuations and hard x-ray emission from the Runaway electrons. MHD activity and hard x-ray intensity were analyzed using Wavelet transform in the presence of external fields and without them. The experimental results showed that the MHD activity and therefore the hard x-ray intensity could be controlled by the external electric and magnetic fields.
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Campos Eletromagnéticos , Elétrons , Raios X , Gases em Plasma , Radiografia , Propriedades de SuperfícieRESUMO
Antibacterial surfaces such as copper coatings are able to reduce the growth of bacteria. In this study, copper coatings was deposited on the 316 stainless steel substrates by a handmade device operating as an atmospheric plasma spraying system. The chemical composition microstructure and morphology surface of the coatings are examined by x-ray diffraction (XRD) and scanning electron microscope (SEM) and back scattering electron microscope (BSE). Micro hardness as one of the key properties of the coating is characterized based on cross-section. We also evaluate the thickness and the adhesion strength of the coating. Dissection material of coating is performed by energy dispersive x-ray spectroscopy (EDX). Further, the antibacterial activity of our coatings is assessed by both gram negative Escherichia coli ATCC 10536 and gram positive Staphylococcus aureus PTCC 1112 bacteria. As the last step, the antibacterial performance of the coated stainless steel surface with copper are compared to uncoated one. Results confirm that the copper coatings improve the antibacterial property of substrates and owning fine antibacterial behavior compared to stainless steel.
Assuntos
Cobre , Desinfetantes , Gases em Plasma/química , Antibacterianos/química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Cobre/química , Cobre/farmacologia , Desinfetantes/química , Desinfetantes/farmacologia , Equipamentos Médicos Duráveis , Teste de Materiais , Aço Inoxidável , Propriedades de Superfície , Difração de Raios XRESUMO
In a tokamak with a toroidal electric field, electrons that exceed the critical velocity are freely accelerated and can reach very high energies. These so-called `runaway electrons' can cause severe damage to the vacuum vessel and are a dangerous source of hard X-rays. Here the effect of toroidal electric and magnetic field changes on the characteristics of runaway electrons is reported. A possible technique for runaways diagnosis is the detection of hard X-ray radiation; for this purpose, a scintillator (NaI) was used. Because of the high loop voltage at the beginning of a plasma, this investigation was carried out on toroidal electric field changes in the first 5â ms interval from the beginning of the plasma. In addition, the toroidal magnetic field was monitored for the whole discharge time. The results indicate that with increasing toroidal electric field the mean energy of runaway electrons rises, and also an increase in the toroidal magnetic field can result in a decrease in intensity of magnetohydrodynamic oscillations which means that for both conditions more of these high-energy electrons will be generated.
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Elétrons , Raios XRESUMO
In this research, the cotton fabrics were treated with nitrogen plasma for the clinical and anti-bacterial purposes. Turmeric was used a as a natural dye. Some part of both untreated and plasma treated samples was immersed in silver nitrate as a mordant before dyeing. Effect of plasma and silver nitrate on dye ability of cotton samples was compared and studied. Samples were analyzed with different experimental methods, such as scanning electron microscopy (SEM), Reflection spectro-photometry and antibacterial test. Results showed that, turmeric dye have anti-bacterial efficiency and good antibacterial activity achieved by plasma treatment of fabrics. In case of AgNO3 treatment, samples showed 100% antibacterial activity. It also concluded that, nitrogen plasma has synergic effect on antibacterial activity of turmeric as natural dye on cotton fabrics.
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Antibacterianos/química , Nanopartículas Metálicas/química , Nitrogênio/química , Gases em Plasma/química , Fibra de Algodão , Curcuma/química , Nitrato de Prata/química , Propriedades de SuperfícieRESUMO
Determinations of plasma parameters as well as the Magnetohydrodynamics (MHD) activity, energetic electrons energy and energy confinement time are essential for future fusion reactors experiments and optimized operation. Also some of the plasma information can be deduced from these parameters, such as plasma equilibrium, stability, and MHD instabilities. In this contribution we investigated the relation between energetic electrons, hard x-ray emission and MHD activity in the IR-T1 Tokamak. For this purpose we used the magnetic diagnostics and a hard x-ray spectroscopy in IR-T1 tokamak. A hard x-ray emission is produced by collision of the runaway electrons with the plasma particles or limiters. The mean energy was calculated from the slope of the energy spectrum of hard x-ray photons.
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Elétrons , Hidrodinâmica , Campos Magnéticos , Magnetismo/instrumentação , Magnetismo/métodos , Raios X , Espectrometria por Raios XRESUMO
Hard x-ray emission from the Runaway electrons is an important issue in tokamaks. Suggesting methods to reduce the Runaway electrons and therefore the emitted hard x-ray is important for tokamak plasma operation. In this manuscript, we have investigated the effects of external fields on hard x-ray intensity and Magneto-Hydro-Dynamic (MHD) activity. In other words, we have presented the effects of positive biased limiter and Resonant Helical Field (RHF) on the MHD fluctuations and hard x-ray emission from the Runaway electrons. MHD activity and hard x-ray intensity were analyzed using Wavelet transform in the presence of external fields and without them. The results show that the MHD activity and therefore the hard x-ray intensity can be controlled by the external electric and magnetic fields.
Assuntos
Campos Eletromagnéticos , Elétrons , Modelos Teóricos , Gases em Plasma , Análise de Ondaletas , Raios XRESUMO
BACKGROUND: Alpha-fetoprotein (AFP)-secreting hepatocellular carcinomas (HCC) represent a genetically distinct subset of tumors often associated with a worse prognosis. However, the molecular mechanisms that underlie these phenotypic differences remain poorly understood. METHODS: HCC tumor samples from 27 patients were profiled using the Affymetrix 133 Plus 2.0 GeneChips. GeneGO Metacore software was used to identify altered biologic pathways. Expression validation was confirmed by RT-PCR. Manipulation of miR-675 by overexpression and antagomir-mediated knockdown was carried out with subsequent evaluation of effects on cell behavior by cell cycle, proliferation, invasion, and growth in soft agar assays. RESULTS: We identified a strong relationship between primary tumor H19 gene expression and elevated serum AFP. H19 has recently been identified to encode microRNA-675 (miR-675), and we confirmed the relationship in an independent sample of patients. Pathway analyses of the effect of miR-675 overexpression in hepatoma cells revealed a predominant upregulation of cell adhesion and cell cycle initiation pathways. We have demonstrated that miR-675 mediates increases in proliferation and an accumulation of cells with tetraploid DNA content associated with a repression of Rb. We also demonstrated that overexpression of miR-675 alters cellular morphology, reduces invasive potential, and increases anchorage-independent growth capacity. These findings are consistent with a mesenchymal-to-epithelial transition, associated with a reduction in the expression of the key EMT mediator, Twist1. CONCLUSIONS: Expression of the miR-675 in hepatocellular carcinoma links a dramatic upregulation of proliferative and growth capacity with inhibition of motility in HCC cells.
Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Proteínas Nucleares/metabolismo , Proteína do Retinoblastoma/metabolismo , Proteína 1 Relacionada a Twist/metabolismo , alfa-Fetoproteínas/metabolismo , Idoso , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Western Blotting , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Adesão Celular , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Feminino , Perfilação da Expressão Gênica , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Luciferases/metabolismo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
In this article, we present a cost-effective approach to the precision measurement of heat flux using commercial thermoelectric modules (TEMs). Two different methods of measuring heat flux with TEMs are investigated, namely, passive mode based on the Seebeck effect and active mode based on the Peltier effect. For both modes, a TEM as a heat flux meter is calibrated to show a linear relation between the voltage across the TEM and the heat flux from 0 to â¼450 W m-2. While both modes exhibit sufficiently high sensitivities suitable for low heat flux measurement, active mode is shown to be â¼7 times more sensitive than passive mode. From the speculation on the origin of the measurement uncertainty, we propose a dual TEM scheme by operating the top TEM in passive mode while its bottom temperature maintains constant by the feedback-controlled bottom TEM. The dual TEM scheme can suppress the sensitivity uncertainty up to 3 times when compared to the single-TEM passive mode by stabilizing the bottom temperature. The response time of a 15 × 15 mm2 TEM is measured to be 8.9 ± 1.0 s for heating and 10.8 ± 0.7 s for cooling, which is slower than commercial heat flux meters but still fast enough to measure heat flux with a time resolution on the order of 10 s. We believe that the obtained results can facilitate the use of a commercial TEM for heat flux measurement in various thermal experiments.
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Antibiotic-resistant Escherichia coli (E. coli) are common in retail poultry products. In this study, we aimed to isolate and characterize multidrug resistant (MDR) E. coli in raw chicken meat samples collected from poultry shops in Sylhet division, Bangladesh, as well as to determine correlation between resistance phenotype and genotype. A total of 600 chicken meat swabs (divided equally between broiler and layer farms, n = 300 each) were collected and the isolates identified as E. coli (n = 381) were selected. Disc diffusion antimicrobial susceptibility assay showed resistance of these isolates to ampicillin, erythromycin, tetracycline, streptomycin, trimethoprim-sulfamethoxazole, chloramphenicol, and gentamicin. Polymerase chain reaction (PCR) identified several antibiotic resistance genes (ARGs) in our isolates. Among these ARGs, the prevalence of tetA (for tetracycline) was the highest (72.58%) in broiler chicken isolates, followed by sul1 (for sulfonamide; 44.16%), aadA1 (for streptomycin; 33.50%), ereA (for erythromycin; 27.41%), aac-3-IV (for gentamicin; 25.38%), and the two genes cmlA (24.87%) and catA1 (8.63%) for chloramphenicol. On the other hand, the respective prevalence in layer chicken isolates were 82.06%, 47.83%, 35.87%, 35.33%, 23.91%, 19.02%, and 5.43%. Furthermore, 49.23% of the isolates from broiler chicken were MDR, with the presence of multiple antibiotic resistance genes, including 3 (40.11%) and 4 (9.13%) genes. On the other hand, 51.09% of layer chicken E. coli isolates were MDR, with 3, 4 or 5 ARGs detected in 36.41%, 14.13%, and 0.54% of the isolates, respectively. We also found that 12.8% of broiler chicken E. coli isolates and 7.61% of layer chicken isolates carried genes coding for extended-spectrum SHV beta-lactamases. Lastly, we report the presence of the AmpC beta-lactamase producing gene (CITM) in 4.56% and 3.26% of broiler and layer chicken E. coli isolates, respectively. We found significant correlations between most of the antimicrobial resistant phenotypes and genotypes observed among the investigated E. coli isolates. Our findings highlight the need for the prudent use of antimicrobials in chickens to minimize the development of antibiotic-resistant bacterial strains.
Assuntos
Galinhas/microbiologia , Farmacorresistência Bacteriana Múltipla/genética , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Carne/microbiologia , Animais , Genes Bacterianos , Genótipo , Testes de Sensibilidade Microbiana , Fenótipo , beta-Lactamases/genéticaRESUMO
A new compound probe is designed, built, and installed on an IR-T1 tokamak to flow measurements in the plasma edge region. The first results of using this probe on the IR-T1 tokamak are presented. The plasma parameters such as plasma current, loop voltage, floating potential, ion and electron saturation currents, electron temperature, plasma potential, and plasma flow velocities are measured in this work. The results show that the electron temperature and the plasma potential in the edge area are 14 eV and 44 V, respectively. The results indicate that the mean value of a parallel Mach number is 0.5 while the mean value of a perpendicular Mach number is almost zero. The large parallel flow velocity (about 17 km/s) and the negligible perpendicular flow velocity are also seen in this work. The most important advantage of using this compound probe is that it can not only save space and vacuum ports but also measure more physical quantities at the same time, contributing to further physical analysis.
RESUMO
BACKGROUND: There is widespread interest in whether psychosis exists on a continuum with healthy functioning. Previous research has implied that paranoia, a common symptom of psychosis, exists on a continuum but this has not been investigated using samples including both patients and non-patients and up-to-date taxometric methods. AIM: To assess the latent structure of paranoia in a diverse sample using taxometric methods. METHOD: We obtained data from 2836 participants, including the general population as well as at-risk mental state and psychotic patients using the P-scale of the Paranoia and Deservedness Scale. Data were analysed using three taxometric procedures, MAMBAC, MAXEIG and L-MODE (Ruscio, 2016), and two sets of paranoia indicators (subscales and selected items from the P scale), including and excluding the patient groups. RESULTS: Eleven of the twelve analyses supported a dimensional model. Using the full sample and subscales as indicators, the MAMBAC analysis was ambiguous. Overall, the findings converged on a dimensional latent structure. CONCLUSIONS: A dimensional latent structure of paranoia implies that the processes involved in sub-clinical paranoia may be similar to those in clinical paranoia.
Assuntos
Comportamento Paranoide/classificação , Transtornos Paranoides/classificação , Adulto , Delusões/classificação , Feminino , Humanos , Masculino , Modelos Teóricos , Análise de Componente Principal , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/classificação , Transtornos Psicóticos/psicologia , Risco , Adulto JovemRESUMO
The human microsomal epoxide hydrolase (EH) gene contains polymorphic alleles, which may be linked to increased risk for tobacco-related lung cancer. The purpose of this study is to screen new polymorphisms and determine whether these polymorphisms can be used to predict individual susceptibility to lung cancer. The polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis was used to screen for polymorphisms in the coding region of the EH gene. Eleven polymorphisms, including previously reported polymorphisms, were identified and the prevalence of these variants was assessed in at least 50 healthy Caucasians and African-Americans. Among the 11 polymorphisms, the prevalence of the amino acid-changing EH polymorphisms in codons 43, 113 and 139 was examined in 182 Caucasian incident cases with primary lung cancer, as well as in 365 frequency-matched controls to examine the role of EH polymorphisms in lung cancer risk. A significant increase in lung cancer risk was observed for predicted high EH activity genotypes (odds ratio (OR) 2.3, 95% confidence interval (CI) 1.2-4.3) as compared with low EH activity genotypes. This association was more pronounced among patients with lung adenocarcinoma (OR 4.7, 95% CI 1.7-13.1). These results suggest that the EH polymorphism plays an important role in lung cancer risk and is linked to tobacco smoke exposure.
Assuntos
Adenocarcinoma/etiologia , Adenocarcinoma/genética , Carcinoma Pulmonar de Células não Pequenas/etiologia , Carcinoma Pulmonar de Células não Pequenas/genética , Epóxido Hidrolases/genética , Predisposição Genética para Doença , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/genética , Polimorfismo Genético , Adulto , Negro ou Afro-Americano/genética , Idoso , Idoso de 80 Anos ou mais , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Reação em Cadeia da Polimerase , Poluição por Fumaça de Tabaco/efeitos adversos , População Branca/genéticaRESUMO
Multifocal presentation, defined as the presence of tumor at two or more anatomically separate sites, before the manifestation of disease in sites where sarcomas usually metastasize (e.g., lungs) occurs in about 1% of extremity soft tissue sarcomas (STSs). Debate still persists whether multifocal STSs represent an unusual pattern of metastasis or multiple separate primary tumors. Among STSs with multifocal presentation, myxoid liposarcoma is the predominant histological type. This subtype of liposarcoma contains the specific t(12;16) chromosomal translocation, which results in rearrangement of the TLS and CHOP genes that is clone specific at the DNA level. We, therefore, sought to address the question of clonality by molecular analysis in six patients who presented with either synchronous or metachronous multifocal myxoid liposarcoma. In all six cases, adequate frozen tumor was available for DNA extraction from at least two distinct anatomical sites. Southern blot analysis using CHOP, TLS, and EWS cDNA probes was performed on genomic DNA. Five cases contained a TLS-CHOP rearrangement, and one case had the variant EWS-CHOP fusion (seen in <5% of cases). The size of the rearranged CHOP fragment differed among the six patients, as expected, but was identical in all anatomically separate tumor samples from each patient. Likewise, the sizes of the rearranged bands observed with either the TLS or EWS probes supported the monoclonality of all cases. Our results confirm the monoclonal origin of multifocal myxoid liposarcoma, establishing the metastatic nature of distant soft tissue lesions in these cases. It remains unclear whether this unusual pattern of metastasis represents an intrinsic property of this subset of myxoid liposarcoma or merely a rare chance occurrence. The clinical outcomes observed in this small series suggest that the prognosis of multifocal myxoid liposarcoma is poor, regardless of its often bland or "low-grade" histological appearance.
Assuntos
Proteínas Estimuladoras de Ligação a CCAAT/genética , Rearranjo Gênico , Lipossarcoma/genética , Neoplasias Primárias Múltiplas/genética , Ribonucleoproteínas/genética , Fatores de Transcrição/genética , Adulto , Idoso , Cromossomos Humanos Par 12 , Cromossomos Humanos Par 16 , Células Clonais , Dano ao DNA , DNA de Neoplasias/isolamento & purificação , Feminino , Ribonucleoproteínas Nucleares Heterogêneas , Humanos , Lipossarcoma/química , Lipossarcoma/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/química , Neoplasias Primárias Múltiplas/patologia , Proteína EWS de Ligação a RNA , Proteína FUS de Ligação a RNA , Proteínas de Ligação a RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição CHOP , Transcrição Gênica , Translocação GenéticaRESUMO
Myxoid liposarcoma (LS), the most common subtype of LS, is known to be characterized by the specific t(12;16) resulting in a TLS-CHOP fusion in almost all cases. We wished to address the following questions: (i) Is this genetic hallmark also present in other types of LS with predominant myxoid change? (ii) What is the proportion of cases with the variant EWS-CHOP fusion? (iii) What is the optimal approach for Southern blot detection of TLS breakpoints? We identified 59 LS characterized histologically by >90% myxoid component, in which frozen tissue tumor was available for DNA extraction. These 59 LS with myxoid features were divided into 2 groups: 42 LS with classic myxoid/round cell appearance (myxoid LS) and 17 well-differentiated LS (WDLS) with a predominant (>90%) myxoid component. Within the myxoid LS group, 29 tumors were low grade and 13 high grade (>20% round cell component). Among the 17 predominantly myxoid WDLS, there were 15 low grade and 2 focally high grade tumors. In addition, we selected as control group, 20 LS of other histological types with minimal or no myxoid change (17 WDLS and 3 pleomorphic LS) and 13 myxofibrosarcomas. Southern blot analysis was performed in all cases using a CHOP cDNA probe, and in all CHOP rearranged cases using a TLS cDNA probe. Probe/enzyme combinations for Southern blot analysis were CHOP exon 3-4 cDNA probe with BamHI or SacI, TLS exon 3-6 cDNA probe with BclI. All 42 cases of myxoid LS showed a CHOP rearrangement and 38 of them also had a TLS rearrangement. Among the 4 myxoid LS without Southern blot evidence of TLS rearrangement, 1 showed an EWS-CHOP fusion by Southern blotting and reverse transcriptase-polymerase chain reaction and in another case, reverse transcriptase-polymerase chain reaction detected a TLS-CHOP fusion transcript. None of the predominantly myxoid WDLS and none of the tumors included in the control group showed rearranegements with CHOP probe. In addition, 12 predominantly myxoid WDLS, 10 other LS, and 5 myxofibrosarcoma from the control group were also tested for TLS rearrangement; all were negative. The TLS-CHOP fusion is highly sensitive and specific for the entity of classic myxoid/round cell LS. Other types of LS, even with a predominant myxoid component, lack the TLS-CHOP rearrangement, confirming that they represent a genetically distinct group of LS. The prevalence of the EWS-CHOP variant fusion was approximately 2% in this series. The optimal enzyme for TLS genomic breakpoint detection is BclI.
Assuntos
Proteínas Estimuladoras de Ligação a CCAAT/genética , Carcinoma de Células Pequenas/diagnóstico , Carcinoma de Células Pequenas/genética , Lipossarcoma Mixoide/diagnóstico , Lipossarcoma Mixoide/genética , Proteínas de Fusão Oncogênica/genética , Southern Blotting , Carcinoma de Células Pequenas/classificação , Quebra Cromossômica/genética , Mapeamento Cromossômico , Fibroma/genética , Ribonucleoproteínas Nucleares Heterogêneas , Histocitoquímica , Humanos , Lipossarcoma Mixoide/classificação , Proteína EWS de Ligação a RNA , Proteína FUS de Ligação a RNA , Ribonucleoproteínas/genética , Fator de Transcrição CHOP , Translocação Genética/genéticaRESUMO
Estimation of the relative risk of cancer due to rare germline mutations using population-based epidemiological techniques is challenging, since studies with very large numbers of subjects are required. In this pilot study using a novel study design, we evaluated the role of INK4A mutations in melanoma by comparing patients with multiple primary melanomas to those with single primaries. Patients were ascertained from the Surgery and Dermatology Clinics at Memorial Sloan-Kettering Cancer Center and at the Yale University Pigmented Lesion Clinic. Subjects completed a questionnaire covering risk factors for melanoma and were tested for INK4A mutations. Five (8%) of 65 patients with multiple primaries had a mutation, compared with none of 88 patients with single primaries (P=0.03). Examination of other factors, such as number of nevi on the arms of the patients, fair skin, hair and eye colour, and other phenotypic characteristics associated with the risk of melanoma, demonstrates that these factors exhibit higher prevalence in the multiple primary cases than in the single primaries. These results provide evidence of the utility of the new study design in evaluating the impact of rare but highly penetrant cancer risk factors.
Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/genética , Melanoma/genética , Neoplasias Primárias Múltiplas/genética , Neoplasias Cutâneas/genética , Adolescente , Adulto , Estudos de Casos e Controles , Cromatografia Líquida , Feminino , Mutação em Linhagem Germinativa/genética , Humanos , Masculino , Melanoma/epidemiologia , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/epidemiologia , Nevo/genética , Desnaturação de Ácido Nucleico/genética , Razão de Chances , Projetos Piloto , Reação em Cadeia da Polimerase , Prevalência , Fatores de Risco , Neoplasias Cutâneas/epidemiologia , Inquéritos e QuestionáriosRESUMO
We have employed cytogenetic and restriction fragment length polymorphism (RFLP) analysis to identify a full spectrum of cytogenetic and molecular alterations associated with initiation and progression of "sporadic" colorectal cancer and also to correlate the alterations with biological and clinical behavior of the tumors. The study series included 63 colorectal cancers, 47 primary and 16 metastatic recurrences. Cytogenetic analysis was successful in 48 tumors (76%) of which 44 (91%) were abnormal. Of these 44 tumors, clonal abnormalities were identified in 43, whereas chromosomes from one tumor were unsuitable for complete analysis. Each of these abnormal tumors displayed heterogeneity with regard to extent and complexity of recurrent chromosomal abnormalities. Numerical losses of chromosomes 17 and 18 (20-34%) and gains of chromosome 7 (28%) were significantly higher. The four most frequent structural rearrangements on the other hand, involved specific regions of chromosomes 1p, 5q, 17p, and 18q. The shortest regions of overlap of these rearrangements or losses were located at 1p36, 5q21-22, 17p13 and 18q21- > ter. RFLP analysis directed at 1p, 5q, 17p and 18q identified allelic deletions of these regions in 39 tumors (64%) which included 17 normal and 11 cytogenetic failures. Of all the informative tumors, 32%, 37%, 31%, and 63% showed allelic losses at chromosomes 1p, 5q, 17p and 18q respectively. The two methods of analysis (cytogenetics and RFLP) employed to identify genetic alterations were complementary; probes for chromosome 1 and 18 showed the greatest degree of concordance, whereas probes for chromosomes 5 and 17 provided relatively higher rate of discordance with cytogenetic results. These differences could be attributed mainly to three reasons: 1) a limited number of probes used for RFLP analysis; 2) contamination of tumor cells with normal cells, and 3) either mutational inactivation or deletion of specific alleles not closely linked to the probes used. Regardless of these limitations, however, the combined use of cytogenetic and RFLP identified genetic alterations in a large number of tumors and help elucidate the role of hyperdiploidy and/or relative deficiency of a given chromosomal segment in expression of recessive mutations. In addition, alterations of either chromosomes 1 or 17 predicted poorer survival for the patients with primary colorectal cancer (p = 0.03).
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Deleção Cromossômica , Cromossomos Humanos Par 17 , Cromossomos Humanos Par 18 , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 5 , Neoplasias Colorretais/genética , Polimorfismo de Fragmento de Restrição , Southern Blotting , Bandeamento Cromossômico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , DNA de Neoplasias/análise , Humanos , Cariotipagem , Metástase Neoplásica , RecidivaRESUMO
Although the transition from early- to advanced-stage ovarian cancer is a critical determinant of survival, little is known about the molecular underpinnings of ovarian metastasis. We hypothesize that microarray analysis of global gene expression patterns in primary ovarian cancer and metastatic omental implants can identify genes that underlie the metastatic process in epithelial ovarian cancer. We utilized Affymetrix U95Av2 microarrays to characterize the molecular alterations that underlie omental metastasis from 47 epithelial ovarian cancer samples collected from multiple sites in 20 patients undergoing primary surgical cytoreduction for advanced-stage (IIIC/IV) serous ovarian cancer. Fifty-six genes demonstrated differential expression between ovarian and omental samples (P < 0.01), and twenty of these 56 differentially expressed genes have previously been implicated in metastasis, cell motility, or cytoskeletal function. Ten of the 56 genes are involved in p53 gene pathways. A Bayesian statistical tree analysis was used to identify a 27-gene expression pattern that could accurately predict the site of tumor (ovary versus omentum). This predictive model was evaluated using an external data set. Nine of the 27 predictive genes have previously been shown to be involved in oncogenesis and/or metastasis, and 10/27 genes have been implicated in p53 pathways. Microarray findings were validated by real-time quantitative PCR. We conclude that gene expression patterns that distinguish omental metastasis from primary epithelial ovarian cancer can be identified and that many of the genes have functions that are biologically consistent with a role in oncogenesis, metastasis, and p53 gene networks.
Assuntos
Genes Neoplásicos , Metástase Neoplásica/genética , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Teorema de Bayes , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Epiteliais e Glandulares/genética , Análise de Sequência com Séries de Oligonucleotídeos , Omento/patologia , Neoplasias Ovarianas/genética , Ovário/patologia , Reação em Cadeia da PolimeraseRESUMO
A FORTRAN computer program was developed to calculate recombination values from F2 data. The input to the program is data on codominant alleles in any number of F2 families segregating for any number of loci, the limit being applied by the computer's memory capacity. For each pair of loci, regardless of the number of segregating progenies used, one recombination value is estimated by the method of maximum likelihood and reported with its standard error. In cases in which more than one family is used for the estimation, the chi-square for the homogeneity of the data also is reported.