RESUMEN
BACKGROUND: About 50% of non-small cell lung cancer (NSCLC) patients develop distant metastases following pulmonary resection. Currently, there are no reliable factors allowing for individual selection of high-risk patients for adjuvant systemic therapies. METHODS: We assessed by quantitative reverse transcription PCR microRNA (miRNA) expression in 273 stage I-IIIA NSCLC samples. Expression of 677 miRNAs was evaluated in fresh-frozen tumour samples in the training cohort of 50 squamous cell carcinoma (SCC) patients who underwent curative surgery. Of those, 20 patients developed distant metastases, and 30 were free of recurrence for >4 years. In the second step, miRNAs with highest predictive value for distant relapse were re-evaluated in formalin-fixed paraffin-embedded material in an independent group of 134 stage I-IIIA SCC patients. Additionally, the same miRNAs were investigated in 89 lung adenocarcinoma (AC) patients and in normal lung parenchyma (NLP). RESULTS: In the training cohort of SCC, six miRNAs were differently expressed in the non-recurrent vs recurrent groups and correlated with distant recurrence-free survival, however none reached the level of significance after correction for multiple testing. Of these six miRNAs, miR-662, -192 and -192* were confirmed as prognostic in the independent SCC cohort. Expression of miR-128, -10b, -502-3p and -192 differed between SCC and AC, and miR-128 and -192 - between NLP and NSCLC. CONCLUSIONS: We identified three new miRNAs predictive of distant relapse in operable SCC. Future miRNA studies should account for differences between NSCLC subtypes.
Asunto(s)
Adenocarcinoma/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/genética , MicroARNs/genética , Adenocarcinoma/patología , Adenocarcinoma del Pulmón , Adulto , Anciano , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Pulmón/patología , Neoplasias Pulmonares/patología , Masculino , MicroARNs/biosíntesis , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Pronóstico , Adulto JovenRESUMEN
OBJECTIVE: Although breastfeeding has been suggested as a candidate for the prevention of obesity and allergies, recent studies have reported mixed results. The aim of the study was (1) to assess breastfeeding length in obese children or children with allergic diseases compared to healthy children; (2) to evaluate the impact of the duration of breastfeeding on the incidence of obesity, allergy rhinitis and asthma. PATIENTS AND METHODS: 408 children were evaluated (mean age 11.9±3.7 years; M/F 220/188) and divided into three groups (Obesity, n=103; Allergy, n=163; and Healthy, n=142). Breastfeeding history was collected during an interview. Physical examination, anthropometry, allergy (skin prick test with aeroallergens; Allergopharma) and a spirometry (Jaeger) assessment were performed in each participant. RESULTS: Most of the children (75%) were breastfed with a mean duration of 7.5 months (range 0-36; SD=7.9 months). The time of breastfeeding was longer in the healthy compared to the obese and allergic groups (p=0.003) and was correlated with BMI centile in all groups of subjects (R Spearman = -0.2, p<0.05). There was a higher number of subjects with hypersensitivity to the allergen of house dust mites and animals in the non-breastfed compared to the breastfed children (p<0.003, p<0.000, respectively). Non-breastfed children compared to the breastfed presented more often asthma (chi2=3.6 df=1 p=0.05), but not allergic rhinitis (chi2=9.0 df=1 p=0.002). Non-breastfed asthmatics, compared to the breastfed asthmatics, presented a significantly higher severity of asthma (OR=0.43; p=0.008). In multivariate regression models, a short breastfeeding time was associated with a higher risk of both obesity and asthma. CONCLUSIONS: School-age children with obesity and asthma were breastfed less often and for a shorter duration than their healthy peers. Longer breastfeeding may result in a reduced number of children with obesity, asthma, and allergy to house dust mites, but further investigation is needed on a larger population of school-age children.
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Asma , Obesidad Infantil , Rinitis Alérgica , Alérgenos , Animales , Asma/epidemiología , Asma/etiología , Lactancia Materna , Niño , Femenino , Humanos , Pyroglyphidae , Rinitis Alérgica/complicacionesRESUMEN
BACKGROUND: Anaphylaxis to insect venom (Hymenoptera) is most severe in patients with mastocytosis and may even lead to death. However, not all patients with mastocytosis suffer from anaphylaxis. The aim of the study was to analyze differences in gene expression between patients with indolent systemic mastocytosis (ISM) and a history of insect venom anaphylaxis (IVA) compared to those patients without a history of anaphylaxis, and to determine the predictive use of gene expression profiling. METHODS: Whole-genome gene expression analysis was performed in peripheral blood cells. RESULTS: Twenty-two adults with ISM were included: 12 with a history of IVA and 10 without a history of anaphylaxis of any kind. Significant differences in single gene expression corrected for multiple testing were found for 104 transcripts (P < 0.05). Gene ontology analysis revealed that the differentially expressed genes were involved in pathways responsible for the development of cancer and focal and cell adhesion suggesting that the expression of genes related to the differentiation state of cells is higher in patients with a history of anaphylaxis. Based on the gene expression profiles, a naïve Bayes prediction model was built identifying patients with IVA. CONCLUSIONS: In ISM, gene expression profiles are different between patients with a history of IVA and those without. These findings might reflect a more pronounced mast cells dysfunction in patients without a history of anaphylaxis. Gene expression profiling might be a useful tool to predict the risk of anaphylaxis on insect venom in patients with ISM. Prospective studies are needed to substantiate any conclusions.
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Anafilaxia/genética , Insectos , Mastocitosis Sistémica/complicaciones , Mastocitosis Sistémica/genética , Ponzoñas/inmunología , Adulto , Anciano , Anafilaxia/etiología , Animales , Estudios de Casos y Controles , Femenino , Perfilación de la Expresión Génica , Humanos , Himenópteros , Masculino , Persona de Mediana Edad , Valor Predictivo de las PruebasRESUMEN
BACKGROUND: Mastocytosis is an uncommon disease resulting from proliferation of abnormal mast cells infiltrating skin, bone marrow, liver, and other tissues. The aim of this study was to find differences in gene expression in peripheral blood cells of patients with indolent systemic mastocytosis compared to healthy controls. The second aim was to define a specific gene expression profile in patients with mastocytosis. METHODS: Twenty-two patients with indolent systemic mastocytosis and 43 healthy controls were studied. Whole genome gene expression analysis was performed on RNA samples isolated from the peripheral blood. For amplification and labelling of the RNA, the Illumina TotalPrep 96 RNA Amplification Kit was used. Human HT-12_V3_expression arrays were processed. Data analysis was performed using GeneSpring, Genecodis, and Transcriptional System Regulators. RESULTS: Comparison of gene expression between patients and controls revealed a significant difference (P < 0.05 corrected for multiple testing) and the fold change difference >2 in gene expression in 2303 of the 48.794 analysed transcripts. Functional annotation indicated that the main pathways in which the differently expressed genes were involved are ubiquitin-mediated proteolysis, MAPK signalling pathway, pathways in cancer, and Jak-STAT signalling. The expression distributions for both groups did not overlap at all, indicating that many genes are highly differentially expressed in both groups. CONCLUSION: We were able to find abnormalities in gene expression in peripheral blood cells of patients with indolent systemic mastocytosis and to construct a gene expression profile which may be useful in clinical practice to predict the presence of mastocytosis and in further research of novel drugs.
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Perfilación de la Expresión Génica , Mastocitosis Sistémica/genética , Transducción de Señal/genética , Transcripción Genética , Adulto , Anciano , Células Sanguíneas/metabolismo , Estudios de Casos y Controles , Femenino , Regulación de la Expresión Génica , Humanos , Masculino , Mastocitosis Sistémica/sangre , Persona de Mediana Edad , ARN Mensajero/análisisRESUMEN
The most important causative factor for anaphylaxis in mastocytosis are insect stings. The purpose of this review is to analyse the available data concerning prevalence, diagnosis, safety and effectiveness of venom immunotherapy (VIT) in mastocytosis patients. If data were unclear, authors were contacted personally for further information. Quality of evidence (A: high, B: moderate, C: low and D: very low) and strength of recommendation (strong 1 and weak 2) concerning VIT in mastocytosis patients are assessed according to the Grading of Recommendations Assessment, Development and Evaluation and are marked in square brackets. Results of VIT were described in 117 patients to date. The mean rate of side-effects during treatment in studies published so far is 23.9% (7.6% requiring adrenaline) with an overall protection rate of 72%. Based on the review we conclude that (1) mastocytosis patients have a high risk of severe sting reactions in particular to yellow jacket, (2) VIT could be suggested [2] in mastocytosis, (3) probably should be done life long [2], (4) VIT in mastocytosis is accompanied by a higher frequency of side-effects, so (5) special precautions should be taken into account notably during the built up phase of the therapy [2], (6) VIT is able to reduce systemic reactions, but to a lesser extent compared to the general insect venom allergic population [2], so (7) patients should be warned that the efficacy of VIT might be less than optimal and they should continue carrying two adrenaline auto injectors [2].
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Anafilaxia/inmunología , Venenos de Artrópodos/uso terapéutico , Mastocitosis/inmunología , Mastocitosis/terapia , Avispas/inmunología , Animales , Venenos de Artrópodos/efectos adversos , Humanos , Inmunoterapia/efectos adversos , Mordeduras y Picaduras de Insectos/inmunología , Mastocitosis/epidemiologíaRESUMEN
BACKGROUND: Mastocytosis is a heterogenous disease involving mast cells (MC) and their progenitors. Cutaneous and systemic variants of the disease have been reported. In contrast to cutaneous mastocytosis (CM), patients with systemic mastocytosis (SM) are at risk to develop disease progression or a nonMC-lineage haematopoietic neoplasm. Little is known, however, about factors predisposing for the development of SM. One factor may be cytokine regulation of MC progenitors. METHODS: We examined the role of the interleukin-13 (IL-13) promoter gene polymorphism -1112C/T, known to be associated with increased transcription, in mastocytosis using allele-specific polymerase chain reaction method. Serum tryptase and IL-13 levels were determined by immunoassay, and expression of the IL-13 receptor in neoplastic MC by reverse transcription-polymerase chain reaction and flow cytometry. RESULTS: The frequency of the -1112T allele of the IL-13 promoter was significantly higher in patients with SM compared with CM (P < 0.008) and in mastocytosis patients compared with healthy controls (P < 0.0001). Correspondingly, the polymorphism was found to correlate with an elevated serum tryptase level (P = 0.004) and with adult-onset of the disease (P < 0.0015), both of which are almost invariably associated with SM. Serum IL-13 levels were also higher in SM patients compared with CM (P = 0.011), and higher in CT- than in CC carriers (P < 0.05). Finally, we were able to show that neoplastic human MC display IL-13 receptors and grow better in IL-13-containing medium. CONCLUSIONS: The -1112C/T IL-13 gene polymorphism and the resulting 'hypertranscription' may predispose for the development of SM.
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Predisposición Genética a la Enfermedad , Interleucina-13/sangre , Interleucina-13/genética , Mastocitosis Sistémica/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Línea Celular Tumoral , Niño , Preescolar , Frecuencia de los Genes , Genotipo , Humanos , Lactante , Interleucina-13/inmunología , Mastocitosis Sistémica/inmunología , Persona de Mediana Edad , Polimorfismo Genético , Regiones Promotoras Genéticas , Receptores de Interleucina-13/genética , Receptores de Interleucina-13/inmunología , Receptores de Interleucina-13/metabolismo , Triptasas/sangre , Triptasas/genética , Triptasas/inmunología , Adulto JovenRESUMEN
Inactivation of TP53 tumor suppressor gene is the most frequent molecular alteration in NSCLC, involving up to 60% of cases. Furthermore, TP53 mutational spectrum is related to the type of mutagen exposure, as well as racial and/or diet differences. Nearly 95% of TP53 perturbations affect codons included within exons 5-8 which encode for almost the entire DNA-binding domain. In this study we addressed the possible prognostic value of the molecular alterations identified in exons 5-8 of the TP53 gene in DNAs from 151 paraffin-embedded NSCLC sections corresponding to 59 Spanish and 92 Polish stage I-IIIA resected patients. PCR/single-strand conformation polymorphism (SSCP) analysis revealed that the occurrence of TP53 exon 5-8 mutations was 17/59 (29%) in the Spanish cohort and 17/92 (18%) in the Polish group. However, when DNA sequencing analysis was performed, these frequencies were reduced because of the presence of SSCP-false positive, intronic and silent mutations and polymorphisms. Fifteen of the 59 Spanish NSCLC tumors (25%) harbored TP53 mutations affecting exons 5-8 coding sequences, whereas only 12 of 92 Polish neoplasms (13%) contained alterations in the central hydrophobic region of p53. Our results indicate that the occurrence of TP53 mutations affecting exon 5-8 coding sequences in some European NSCLC populations may be lower than previously reported, and that the TP53 mutational patterns of these cohorts differ somewhat. The Spanish NSCLC patients contained missense mutations (9/59, 15%) and a relatively high percentage of null mutations (5/59, 8%) while the Polish patients mostly harbored missense mutations (9/92, 10%) and only one tumor contained a null type (1/92, 1%). Moreover, most TP53 missense mutations in the Spanish group were located outside the conserved regions, whereas the same mutations in the Polish group affected conserved amino acids. Furthermore, the Polish patients harbored a high percentage of G-->A transitions (most of them at non-CpG sites), while G-->T transversions were predominant in the Spanish group. Our findings suggest that there may be different racial or exogenous factors in these two populations which may help to explain both the distinct TP53 mutational pattern and the lower frequency obtained in the Polish group. The presence of missense mutations did not confer a worse clinical outcome in these subsets of NSCLC patients. However, patients whose tumors contained null TP53 gene mutations had a 5 month median disease-free survival time in contrast with 42 months in those patients without mutations (P=0.008). These findings suggest that loss of p53 function may enhance tumor progression in NSCLC patients independently of whether dominant negative TP53 missense mutations are present.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Genes p53 , Neoplasias Pulmonares/genética , Mutación , Anciano , Sustitución de Aminoácidos/genética , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Análisis Mutacional de ADN , Supervivencia sin Enfermedad , Femenino , Mutación del Sistema de Lectura , Eliminación de Gen , Frecuencia de los Genes , Humanos , Neoplasias Pulmonares/epidemiología , Masculino , Persona de Mediana Edad , Polonia/epidemiología , Pronóstico , España/epidemiologíaRESUMEN
PURPOSE: The aim of this study was to assess the prognostic relevance of apoptotic index (AI), considered alone or together with expression of several proteins controlling G1 check point (p53, mdm2, pRb and p21WAF1/CIP1) in non-small cell lung cancer (NSCLC) patients. METHODS: Study group included 50 NSCLC patients who underwent curative pulmonary resection. Apoptosis was detected with the use of TUNEL technique and AI was defined as the number of apoptotic cells per 1,000 tumor cells. The expression of p53, mdm2, pRb and p21WAF1/CIP1 was assessed immunohistochemically. RESULTS: The mean and median AI calculated for all 50 patients was 14 and 9, respectively. Patients with lower (<14) and higher (> or =14) AI constituted 35 (70%) and 15 (30%) of cases, respectively. AI was not correlated with patient clinical characteristics, and expression of p53, pRb and p21WAF1/CIP1 . However, lower AI was correlated with over-expression of mdm2 protein (P=0.04). Median survival for patients with lower and higher AI was 43 months and 22 months, respectively, and 5-year survival probability-60 and 25%, respectively (P=0.03). In multivariate analysis, the only variable associated with shortened survival was AI (P=0.03, HR=2.9, 95% CI 1.95-3.86). CONCLUSIONS: These results suggest that AI correlates with mdm2 protein expression and influences survival in NSCLC.
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Apoptosis/fisiología , Biomarcadores de Tumor/análisis , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , Anciano , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/análisis , Femenino , Humanos , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Pronóstico , Proteínas Proto-Oncogénicas c-mdm2/biosíntesis , Proteína de Retinoblastoma/biosíntesis , Análisis de Supervivencia , Tasa de Supervivencia , Proteína p53 Supresora de Tumor/biosíntesisRESUMEN
Serum levels of NSE were monitored in 20 SCLC patients who completely responded to combination chemotherapy. An elevation of NSE was observed in five of nine patients with recurrent disease, but predated a relapse in only one. No elevation in NSE level was noted in nine patients who remained in complete remission. The addition of serial assays of LDH to NSE monitoring did not result in any gain in early warning of relapse. This study suggests that the value of serial NSE measurements for predicting a relapse of disease is limited.
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Biomarcadores de Tumor/sangre , Carcinoma de Células Pequeñas/secundario , Neoplasias Pulmonares/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Fosfopiruvato Hidratasa/sangre , Adulto , Anciano , Carcinoma de Células Pequeñas/diagnóstico , Carcinoma de Células Pequeñas/enzimología , Femenino , Humanos , Neoplasias Pulmonares/enzimología , Masculino , Persona de Mediana EdadRESUMEN
10 patients with locally advanced bronchioloalveolar carcinoma were treated with interferon-alpha as an inhaled aerosol. Initial doses ranged between 1 and 10 MU daily or thrice weekly and were then increased to 20 MU daily. Treatment was continued until disease progression or excessive toxicity occurred, 9 patients were evaluable for toxicity. In 1 case treatment had to be stopped after 2 weeks due to fever, fatigue and progressive dyspnoea. 2 patients developed fever, 1 had malaise, fatigue and loss of appetite and 2 had dose-dependent transient dyspnoea. According to standard criteria no tumour responses could be detected. In 6 out of 8 evaluated for response to interferon, radiological stabilisation of disease for 7-43 weeks (median 15) was observed. These results point to the feasibility of aerosol inhalation of interferon-alpha, but also to its limited antitumour activity in locally advanced bronchioloalveolar carcinoma.
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Adenocarcinoma Bronquioloalveolar/terapia , Interferón Tipo I/administración & dosificación , Neoplasias Pulmonares/terapia , Administración por Inhalación , Adulto , Aerosoles , Anciano , Femenino , Humanos , Interferón Tipo I/efectos adversos , Interferón Tipo I/uso terapéutico , Masculino , Persona de Mediana Edad , Proteínas RecombinantesRESUMEN
The prognostic value of serum neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) was prospectively assessed in 42 patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) treated within two chemotherapy trials. Pretreatment NSE levels ranged from 4.6 to 34.6 ng/mL (median value, 7.5) and were above 10 ng/mL in ten patients (23.8%). LDH levels varied between 85 U/L and 2,484 U/L (median value, 220) and were above 250 U/L in 12 patients (29.3%). Elevated levels of both enzymes were significantly more common in patients with metastatic disease than in those with locoregional disease (40% v 9% for NSE and 40% v 18% for LDH, respectively). Strong positive correlation (correlation factor 0.693) was found between NSE and LDH serum levels. The levels of both markers did not correlate with age, sex, previous therapy, performance status, or histology. Responses to chemotherapy were seen more frequently in patients with elevated NSE levels (six of ten, 60%) than in those with normal values (seven of 32, 22%; P = .02). Similar correlation was found for LDH: Response was seen in seven of 12 patients with elevated levels (58%) and in six of 29 (21%) of those with normal values (P = .02). In a logistic regression analysis, both markers considered individually remained significant when adjusted by sex, age, performance status, prior therapy, histology, and extent of disease. Three pretreatment characteristics, high levels of NSE and LDH (both considered as continuous variables) and metastatic disease, were found to be associated with shorter survival; with adjustment for extent of disease, however, NSE and LDH were no longer correlated with shorter survival. These data suggest potential clinical value of NSE and LDH determination in treatment selection of NSCLC patients.
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Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/enzimología , L-Lactato Deshidrogenasa/sangre , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/enzimología , Fosfopiruvato Hidratasa/sangre , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/administración & dosificación , Etopósido/administración & dosificación , Femenino , Humanos , Ifosfamida/administración & dosificación , Masculino , Mesna/administración & dosificación , Persona de Mediana Edad , Probabilidad , Estudios Prospectivos , Inducción de Remisión , Tasa de SupervivenciaRESUMEN
OBJECTIVE: Prognostic relevance of the current TNM stage grouping for lung cancer is still a matter of debate. METHODS: To validate the new pathologic TNM classification for non-small cell lung cancer, we analyzed the survival data of 586 patients who underwent complete pulmonary resection and pathologic staging at one institution. RESULTS: The current TNM stage grouping well reflected the long-term prognostic hierarchy. There was a good distinction between new substages IA and IB (5-year survivals of 66% and 53%, respectively). The subdivision of stage II led to an under-representation of stage IIA (6 patients [1.0%]), and therefore the appropriateness of this modification could not be verified. Five-year survival in the T3 N0 category (30%) was significantly better than that found in the new stage IIIA (15%). No difference was found between T3 N0 and T2 N1, the categories constituting new stage IIB. Within stage IIIA there was a significant survival difference between T3 N2 (6%) and the remaining T and N designations (18%). Moreover, the 5-year survival in the T3 N1 category (35%) was similar to that found in the new stage IIB (27%) and better than in any T N2 tumors (12%). CONCLUSION: Most of our findings confirmed prognostic relevance of the current pTNM stage grouping in patients with resectable non-small cell lung cancer. However, despite recent modifications, there is still a significant heterogeneity that flaws stage IIIA.
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Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Femenino , Humanos , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Tasa de SupervivenciaRESUMEN
Prognostic value of p53 and PCNA expression in non-small cell lung cancer (NSCLC) remains controversial. In this study we determined the relevance of these abnormalities in terms of overall survival and disease-free survival in 95 NSCLC patients who underwent curative pulmonary resection. Expression of p53 was found in 44 samples (45%), expression of PCNA-in 79 samples (83%), and expression of both markers-in 35 samples (36%). There was no relationship between expression of either protein and major clinicopathological characteristics. Median survival for patients with and without p53 expression was 36 and 33 months, respectively and 5-year survival probability-29 and 37%, respectively (P=0.73). Median survival for patients with and without PCNA expression was 36 and 27 months, respectively and 5-year survival probability-35 and 25%, respectively (P=0.60). There was no significant difference in overall survival between particular groups of patients with tumors carrying four possible p53/PCNA phenotypes. In multivariate analysis including patient age, sex, tumor stage, tumor type and differentiation, p53 and PCNA expression, the only variable important for survival was stage of disease. These results suggest the lack of prognostic relevance of p53 and PCNA expression in surgically treated NSCLC patients.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Antígeno Nuclear de Célula en Proliferación/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidad , Adulto , Anciano , Carcinoma de Células Grandes/diagnóstico , Carcinoma de Células Grandes/metabolismo , Carcinoma de Células Grandes/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidad , Diferenciación Celular , Supervivencia sin Enfermedad , Femenino , Humanos , Técnicas para Inmunoenzimas , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Tasa de SupervivenciaRESUMEN
Mutations of p53 suppressor gene are among the most common molecular abnormalities in human malignancies. We demonstrated earlier significant differences in mutational profiles between NSCLC patients from Poland and Spain. These differences were most probably related to ethnic and/or geographical factors. In the present study we analyzed the types and location of p53 gene mutations in a large group of 332 operated NSCLC patients from two institutions in Northern Poland. Within the last decades this region has been characterized by the highest incidence of lung cancer in Poland. We used both frozen and paraffin-embedded tumor samples and the screened region included exons from 5 to 8. A total of 96 samples (29%) were positive for p53 gene mutation. The proportion of mutations in particular exons was as follows: exon 5-33%, exon 6-22%, exon 7-16%, and exon 8-29%. Three 'hot spots' were located in codons 176,245 and 248. Evolutionary conserved domains were much more frequently affected than the regions outside domains. The majority of mutations (73%) were missense type, followed by null and silent mutations (21 and 6%, respectively). In all six silent mutations substituted was the third base in codon. There were no major differences in the types and locations of mutations between patients from the two institutions. This homogeneity, together with our earlier findings, may confirm the impact of ethnic and geographical factors on the mutational profile of p53 gene in NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Análisis Mutacional de ADN , Genes p53/genética , Neoplasias Pulmonares/genética , Anciano , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/patología , Etnicidad , Exones/genética , Femenino , Geografía , Humanos , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Mutación Missense , Polonia/epidemiologíaRESUMEN
From March 1987 to February 1991, 136 patients with untreated small cell lung cancer (64 patients with limited disease and 72 with extensive disease), were treated as part of a prospective multi-center study, with a combination of cyclophosphamide 1000 mg/m2 i.v. on day 1, epirubicin 70 mg/m2 i.v. on day 1 and etoposide 100 mg/m2 i.v. on days 1, 3 and 5. Courses were repeated every 3 weeks. One-hundred thirty-four patients were evaluable. There were 42 (31%) complete responses and 66 (49%) partial responses for an overall response rate of 80% (95% confidence interval 71-87%). A complete response was seen in 24 patients (38%) with limited disease and in 18 patients (26%) with extensive disease, while a partial response was observed for 31 (48%) and in 35 (50%) patients, respectively. The median duration of response for all patients was 8.9 months (range, 1-60+ months). The median duration of survival for the entire group was 11.4 months (12.5 months for limited disease and 9.8 months for extensive disease). The 2-year survival rate for the whole group was 13%. The main side-effects were myelosuppression, alopecia, nausea and vomiting. Grade 4 toxicity was seen in 8.5% of patients. In conclusion, the studied regimen was found to be active and well tolerated and may be considered as an alternative to standard chemotherapy combinations in SCLC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/administración & dosificación , Epirrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Prognostic relevance of serum p53 antibodies was assessed in 96 patients with microscopically proven small cell lung cancer (SCLC). The study group included 67 males and 29 females; mean age 58 years; range 35--86 years; 60 with limited disease (LD), and 36 with extensive disease (ED). The control group consisted of 41 patients with non-malignant diseases. The presence of p53 antibodies was assayed by the immunoenzymatic method (P53 ELISA kit, PharmaCell, France). Antibodies were present in 26 SCLC cases (27%); 15 (25%) in LD and 11 (31%) in ED. Antibodies were also found in one out of 41 control subjects (2%). There was no correlation between the level of antibodies and clinical characteristics of SCLC patients including age, gender and extent of disease. The median follow-up for the entire group was 30 months (range: 11--39 months). By the time of analysis, 78 patients (82%) had deceased. Median survival in SCLC patients with and without antibodies was 42 and 39 weeks, respectively (log rank, P=0.81). These results indicate the lack of clinical relevance of serum p53 antibodies in SCLC.
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Anticuerpos Antineoplásicos/análisis , Carcinoma de Células Pequeñas/inmunología , Neoplasias Pulmonares/inmunología , Proteína p53 Supresora de Tumor/inmunología , Adulto , Anciano , Carcinoma de Células Pequeñas/patología , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de SupervivenciaRESUMEN
SETTING: The prevalence of cigarette smoking in Poland is one of the highest in Europe. OBJECTIVE: To compare the frequency of smoking among Polish pupils during a school year and the summer holidays. DESIGN: A questionnaire including personal and demographic data and information on smoking behaviour was distributed among 598 school pupils: 357 girls and 241 boys aged 8-19 years, with a mean age of 14.4. RESULTS: Among the entire group of school pupils, 18.6% were cigarette smokers. Half of the smokers smoked occasionally and the remainder smoked every day; of these, 9.9% smoked more than 10 cigarettes daily. The frequency of smoking among these teenagers increased with age. The average age of smoking initiation was 13 years for boys and 15 years for girls. The majority smoked more during the summer holidays than during the school year. The most frequently reported reasons for increasing cigarette smoking during the summer holidays were: feeling more free, having more money to spend, the influence of new friends, and smoking to pass the time when they felt bored. CONCLUSION: Young people in this study still started smoking early, most frequently between the ages of 13 and 15. High rates of daily smokers among teenagers were observed. In some groups of teenagers the summer holidays may be a time of increased cigarette smoking.
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Vacaciones y Feriados , Fumar/epidemiología , Adolescente , Niño , Femenino , Humanos , Masculino , Polonia/epidemiología , PrevalenciaRESUMEN
The assessment of tumour angiogenesis in NSCLC is presently a subject of intensive research with potential clinical applications. In this study, the expression of VEGF and FLK-1 was examined by immunohistochemistry in 67 archival tumour samples obtained from NSCLC patients treated by radical resection. Distribution of age, sex, tumour stage and histology was typical for patient population in Poland. VEGF expression (more than 25% of positive cells) was noted in 65% of tumour cells. FLK-1 expression was observed in 91% of tumour cells. Neither the number of positive cells nor the staining intensity correlated with the clinical variables (all p values >0.05, chi-square test). No correlation was noted between the expression of VEGF and FLK-1 (p=0.35, chi-square test). In survival analysis, neither the number of positive cells nor the staining intensity of both molecules was of prognostic significance. The expression of VEGF and FLK-1 in NSCLC cells was confirmed in this study. The relation to clinical variables and survival will be further assessed in a larger group of patients.
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Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Factores de Crecimiento Endotelial/biosíntesis , Neoplasias Pulmonares/metabolismo , Linfocinas/biosíntesis , Proteínas Tirosina Quinasas Receptoras/biosíntesis , Receptores de Factores de Crecimiento/biosíntesis , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Factores de Crecimiento Endotelial/análisis , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Linfocinas/análisis , Masculino , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Proyectos Piloto , Valor Predictivo de las Pruebas , Proteínas Tirosina Quinasas Receptoras/análisis , Receptores de Factores de Crecimiento/análisis , Receptores de Factores de Crecimiento Endotelial Vascular , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
The aim of this study was to assess the occurrence of anaerobic non-sporeforming bacteria upper airways flora in the exacerbation of COPD. Sputum from 35 COPD patients was sent to the laboratory in sterile, filled with CO2 containers and cultured under anaerobic conditions. In all patients bacteriological tests were positive. The most common anaerobic bacteria were as follows: Peptostreptococcus - in 28 pts, Fusobacterium - in 27 pts, Bacteroides - in 26 pts and Prevotella in 24. Less common were: Propionibacterium, Actinomyces, Eubacterium, Porphyromonas and Peptococcus. The susceptibility to most common antimicrobial agents was evaluated. All anaerobic bacteria show a significant sensitivity to amoxicillin either with clavulanic acid or ampicillin with sulbactam. Gram-positive rods were resistant to metronidazole and tinidazole.
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Bacterias Anaerobias/aislamiento & purificación , Enfermedades Pulmonares Obstructivas/microbiología , Adulto , Anciano , Bacterias Anaerobias/efectos de los fármacos , Bacteroides/aislamiento & purificación , Farmacorresistencia Microbiana , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Peptostreptococcus/aislamiento & purificación , Prevotella/aislamiento & purificación , Esputo/microbiologíaRESUMEN
For evaluation of usefulness of natural fluorescence of clinical materials in UV radiation as rapid diagnostic method of infections with anaerobes, 405 samples of pus, bloody-purulent fluids, blood, wound secretions, dressings and other materials were investigated. Occurrence of red-brick UV fluorescence of clinical materials was compared with results of culture aimed at isolation of non-sporeforming anaerobes from "B. melaninogenicus group (P. melaninogenica, P. intermedia and P. saccharolytics). Significant correlation red-brick fluorescence of clinical materials resulting from UV irradiation with presence in these materials of anaerobes such as P. melaninogenica, P. intermedia and P. asaccharolytics was detected. Investigation of clinical materials with application of fluorescence in UV radiation lasts only 1-2 minutes and together with preparation and microscopical inspection which is Gram-stained--only 15-20 min. Positive results of this test may constitute a basis for rapid, preliminary identification of the etiologic factor and for direction of chemotherapy in the early period of infection.