RESUMO
BACKGROUND: This randomized, double-blind, placebo-controlled, phase II study evaluated the efficacy and safety of mapatumumab (a human agonistic monoclonal antibody against tumor necrosis factor-related apoptosis-inducing ligand receptor 1) in combination with sorafenib in patients with advanced hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Patients with advanced HCC (stratified by Barcelona Clinic Liver Cancer stage and Eastern Cooperative Oncology Group performance status) were randomized 1:1 to receive sorafenib (400 mg, twice daily per 21-day cycle) and either placebo (placebo-sorafenib arm) or mapatumumab (30 mg/kg on day 1 per 21-day cycle; mapatumumab-sorafenib arm). The primary end point was time to (radiologic) progression (TTP), assessed by blinded independent central review. Key secondary end points included progression-free survival, overall survival, and objective response. RESULTS: In total, 101 patients were randomized (placebo-sorafenib arm: N = 51; mapatumumab-sorafenib arm: N = 50). There was no significant difference in median TTP between both arms [5.6 versus 4.1 months, respectively; adjusted hazard ratio (one-sided 90% confidence interval) 1.192 (0-1.737)]. No mapatumumab-related benefit was identified when TTP was evaluated in the stratified subgroups. The addition of mapatumumab to sorafenib did not demonstrate improvement in the secondary efficacy end points. The reported frequency of adverse events (AEs) and serious AEs was comparable in both treatment arms. CONCLUSIONS: The addition of mapatumumab to sorafenib did not improve TTP or other efficacy end points, nor did it substantially change the toxicity profile of sorafenib in patients with advanced HCC. Based on these results, further development of the combination of mapatumumab and sorafenib in HCC is not planned.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Niacinamida/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Sorafenibe , Resultado do TratamentoRESUMO
OBJECTIVES: Malignant lymphomas of larynx and trachea are rare tumors and require special diagnostic and therapeutic attention. The authors present an unexpected case of nonHodgkin Lymphoma localized in the subglottic larynx and upper cervical trachea. The clinical presentation, diagnostic and therapeutic approach, evolution and prognosis are discussed. METHOD: We report a case of 25-year-old male patient, with progressive dyspnea, presented in our ENT Department with severe airway obstruction caused by a large subglottic tumoral mass migrated in the glottic space during an accidental fall. An emergency tracheotomy was performed. The flexible endoscopy and CT-scan revealed a large mass arising from the subglottic larynx and anterior wall of upper cervical trachea with the obstruction of 2/3 of the laryngotracheal lumen. RESULTS: After a complex assessment, the tumor was excised by external approach (median thyrotomy). The histopathologic exam of the surgical specimen showed malignant nonHodgkin lymphoma and the immunohistochemical profiles were evaluated in order to establish the therapeutic strategy including chemotherapy in the Department of Oncology. CONCLUSIONS: Invasion of the subglottic larynx and trachea by lymphoma is an uncommon problem which can cause severe airway obstruction and requires multidisciplinary approach (ENT, pneumology, oncology/hematology). The clinicopathological features of this case have been described and compared with previously reported cases.
Assuntos
Neoplasias Laríngeas/patologia , Linfoma de Células B/patologia , Neoplasias da Traqueia/patologia , Adulto , Obstrução das Vias Respiratórias/etiologia , Quimioterapia Adjuvante , Diagnóstico Diferencial , Humanos , Neoplasias Laríngeas/complicações , Neoplasias Laríngeas/terapia , Linfoma de Células B/complicações , Linfoma de Células B/terapia , Masculino , Radioterapia Adjuvante , Neoplasias da Traqueia/complicações , Neoplasias da Traqueia/terapia , Traqueotomia , Resultado do TratamentoRESUMO
The authors present a case of colonic monoblastic sarcoma, previously treated for other digestive abnormalities (malabsorbtion, Hirschprung's disease). Important similitudes with immunoproliferative small intestinal disease (IPSID) lymphoma were demonstrated for this patient (male, 2-year-old). His main admission complaints were failure to thrive, recurrent episodes of enterocolitis and malabsorbtion syndrome. Some particularities of this case are the young age and the extremely rapid development of the malignant disease in a patient with no previous signs of acute non-lymphoblastic leukemia. The initial diagnosis was of malabsorbtion syndrome, based on the clinical exam at presentation, and then the patient was thought to have a form of Hirschprung's disease, due to a functional intestinal disorder (slow transit). After the necropsy, pathologists diagnosed an immunoproliferative small intestinal disease, and four years later, they performed a more appropriate pathological exam, which explained better clinical symptoms associated to this complex case.
Assuntos
Neoplasias do Colo/diagnóstico , Doença Imunoproliferativa do Intestino Delgado/diagnóstico , Sarcoma/diagnóstico , Pré-Escolar , Diagnóstico Diferencial , Doença de Hirschsprung/diagnóstico , Humanos , Síndromes de Malabsorção/diagnóstico , MasculinoRESUMO
Pre-heating of serum samples has been shown to reverse false negative antigen tests for Dirofilaria immitis infection in dogs. Here the authors report the results of serum sampling in a population of dogs naturally exposed to D. immitis and Dirofilaria repens infection by testing in ELISA before and after heat treatment. Of 194 dogs sampled from four cities in Romania, D. immitis circulating antigens were found in 16 (8.2%) non heated samples and in 52 (26.8%) heated samples. Of the 108 dogs examined by Knott test, 24 dogs (22.2%) were positive for circulating mf. Subsequent PCR identification showed six dogs had D. immitis mf only, 12 dogs, had only D. repens mf, and 5 were positive for both. Fifty% of dogs with circulating D. immitis mf had positive antigen tests before and after heating, while the other 50% reverted to positive only after heat treatment. Sixty% of dogs with mixed D. immitis/D. repens infection were antigen positive before and after heating, while the other 40% converted to positive after heating. Antigen testing for D. immitis in the 12 dogs with only D. repens mf gave conflicting results. Only two dogs (16%) were antigen negative both before and after heat treatment. Six dogs (50%) became antigen positive after heating and four dogs (30%) were antigen positive both before and after heat treatment. Results would suggest that: false negative result for antigen testing can be reverted by heating of the serum sample; dogs infected with D. repens may have also an occult infection with D. immitis; heat treatment of serum from D. repens-infected dogs can reveal an occult infection with D. immitis.
Assuntos
Técnicas e Procedimentos Diagnósticos/veterinária , Dirofilariose/diagnóstico , Doenças do Cão/diagnóstico , Ensaio de Imunoadsorção Enzimática/veterinária , Temperatura Alta , Animais , Antígenos de Helmintos/sangue , Dirofilaria immitis , Dirofilaria repens , Dirofilariose/epidemiologia , Doenças do Cão/epidemiologia , Cães , Ensaio de Imunoadsorção Enzimática/normas , Reações Falso-Negativas , Reação em Cadeia da Polimerase/veterinária , Romênia/epidemiologiaRESUMO
The influence of streptomycin and neomycin upon the conformation of the ribosome has been investigated using spin-labeled and fluorescent analogs of the sulfhydryl reagent, N-ethylmaleimide. Changes in the electron paramagnetic resonance spectra or in the polarization of fluorescence of labeled ribosomes reveal that streptomycin alters the mobility of labels bound to the sulfhydryl group of protein S18 while neomycin affects the mobility of labels bound to the sulfhydryl groups of proteins S1, S21 and/or L10. It is also observed that both streptomycin and neomycin interfere with changes in the mobility of labels induced by storage under inactivating conditions. From these results, it is concluded that: 1. streptomycin and neomycin distort the conformation of the ribosome at different sites, streptomycin disturbing preferentially the area around the sulfhydryl group of protein S18 while neomycin affects the environment of the sulfhydryl groups of proteins S1, S21 and/or L10; 2. streptomycin and neomycin interefere with the ability of the ribosome to undergo conformational changes.
Assuntos
Escherichia coli/ultraestrutura , Neomicina/farmacologia , Ribossomos/ultraestrutura , Estreptomicina/farmacologia , Ácido Edético/farmacologia , Espectroscopia de Ressonância de Spin Eletrônica , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Etilmaleimida/metabolismo , Ribossomos/efeitos dos fármacos , Ribossomos/metabolismo , Espectrometria de Fluorescência , Marcadores de SpinRESUMO
In a poly(U)-programmed translation system, neomycin stimulates the misincorporation of tyrosine and of serine which, according to Thompson and Stone (Thompson, R.C. and Stone, P.J. (1977) Proc. Natl. Acad. Sci. USA. 74, 198-202), are normally rejected at an initial discrimination step during the binding of charged tRNAs to the ribosome. In contrast, streptomycin favors the misincorporation of isoleucine which is normally rejected at a subsequent GTP-dependent discrimination step, the so-called proofreading step. The labeling of the ribosome with N-ethylmaleimide mimics the effect of streptomycin in that it stimulates the misincorporation of isoleucine but not of tyrosine or serine. This effect is correlated with the labeling of protein S18 but not with that of protein S1. These observations indicate that the sulfhydryl group of protein S18 is located within a ribosomal domain involved in the proofreading control of tRNA selection. Taking into account our previous results that streptomycin and neomycin perturb ribosomal areas around the sulfhydryl groups of proteins S18 and S1, respectively, we suggest that these antibiotics induce misreading by different mechanisms which are linked to such perturbations.
Assuntos
Neomicina/farmacologia , Biossíntese de Proteínas/efeitos dos fármacos , Estreptomicina/farmacologia , Escherichia coli , Etilmaleimida/farmacologia , Isoleucina/metabolismo , Leucina/metabolismo , Poli U/metabolismo , Ribossomos/efeitos dos fármacos , Serina/metabolismo , Tirosina/metabolismoRESUMO
AIM: Clinical-epidemiological investigations for further assessing the importance of video-assisted thoracoscopy in the treatment y of patients with neoplastic pleurisy. MATERIALS AND METHODS: The researches included a group of 72 patients (31.9% men and 68.1% women aged 31-81 years, mean age ± 60 years) with neoplastic pleurisy who underwent pleural symphysis by video-assisted thoracoscopic talcage. For statistical-mathematical processing and interpretation the Pearson correlation index with the level of significance at p = 0.05 and highly significant at p < 0.005 was used. RESULTS: Neoplastic pleurisy prevalently affected the age groups 51-80 years (84.9%). Dyspnea was present in all cases, and patient history at the time of admission revealed 14 conditions, of which 25% were lung cancers. Macroscopically nodular and vegetative tumors were found in 66.7% of cases. An amount of 1000-2000 ml of pleural fluid was found in 44.5% of the cases and a serocitrin appearance in 50%. In 23.6% of the cases cytology results were positive for malignancy and in 13.8% suspicious. In 65.2% of the cases the pleural fluid was exudative and anatomopathology was suggestive of adenocarcinoma in 34.7% of the cases and breast cancer in 18%. The prevalence of recurrences varied from 1 month to more than 7 months, with 36.4% for 1-2 months. CONCLUSIONS: The obtained additional data support the important role of pleural symphysis by video-assisted thoracoscopic talcage in the patients with neoplastic pleurisy.
Assuntos
Neoplasias Pulmonares/complicações , Neoplasias Pleurais/complicações , Pleurisia/cirurgia , Pleurodese , Talco/administração & dosagem , Cirurgia Torácica Vídeoassistida , Toracoscopia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Excipientes/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pleurisia/epidemiologia , Pleurisia/etiologia , Prevalência , Fatores de Risco , Romênia/epidemiologia , Resultado do TratamentoRESUMO
Cytotoxicity of arabinofuranosylcytosine (ara-C) has been related in vitro to the inhibition of the DNA polymerase activities by arabinosylcytosine triphosphate (ara-CTP) and the incorporation of ara-C into the DNA where, acting as a chain terminator, it slows the chain elongation. Induced in vitro cellular resistance to ara-C was shown to be secondary to altered deoxycytidine (dCyd) kinase activity, dCyd deaminase activity, or deoxynucleotides triphosphates (dNTP) pools. Recent studies reported no differences of ara-C metabolism in cells obtained from leukemic patients at diagnosis and at relapse after ara-C therapy, suggesting that unknown cellular biochemical determinants may be involved in acquisition of ara-C resistance. Using dialysed crude extracts of leukemic cells obtained from patients at diagnosis, we observed variable inhibition of their DNA polymerase activities by arabinosylcytosine monophosphate (ara-CMP) at 2 mmol/L (0% to 50% inhibition). In similar conditions, ara-CMP reduced the polymerase activities of human thymus extract by 35% and 55% in extract of HL-60 cells (cultured human promyelocytic cells). The ara-CMP factor responsible for inhibition of DNA polymerase activity was nondialysable, heat labile, proteinase K sensitive, and has an estimated molecular mass of 30 kilodalton by gel filtration. After partial purification, this protein had no DNA polymerase RNA polymerase activities. In presence of the regulator and ara-CMP at 2 mmol/L, we observed no inhibition of the HL-60 3'----5' and 5'----3' exonucleases activities, suggesting the regulator interaction being mainly with the DNA polymerases in presence of ara-CMP. The relevance of the presence or absence of this protein regarding the cell sensitivity to ara-C is under investigation.
Assuntos
Arabinonucleotídeos/farmacologia , Monofosfato de Citidina/farmacologia , Nucleotídeos de Citosina/farmacologia , DNA Polimerase II/antagonistas & inibidores , Proteínas de Ligação a DNA/fisiologia , Leucemia/fisiopatologia , Doença Aguda , Linhagem Celular , Monofosfato de Citidina/análogos & derivados , Monofosfato de Citidina/metabolismo , Desoxicitidina Monofosfato/metabolismo , Humanos , Leucemia Mieloide Aguda/enzimologia , Peso Molecular , Uridina Monofosfato/metabolismoRESUMO
Splenic lymphocytes from chickens bearing tumors induced by avian sarcoma virus are able to cause the specific killing of cultured avian sarcoma cells. This cytotoxicity appears to follow classical patterns of syngeneic restriction. Little or no specific killing of tumor targets occurred when spleen cells from one inbred line of chickens were tested against allogeneic targets, although syngeneic killing proceeded relatively efficiently. Other patterns of immune reactivity did not appear to be syngeneically restricted. Namely, sera from tumor-bearing hosts were equally reactive in indirect immunofluorescence assays with syngeneic and allogeneic target cells. And, peripheral blood lymphocytes from sensitized hosts could be stimulated equally well by tumor cell culture fluids of allogeneic or syngeneic origin.
Assuntos
Citotoxicidade Imunológica , Linfócitos/imunologia , Sarcoma Aviário/imunologia , Animais , Antígenos Virais/imunologia , Vírus do Sarcoma Aviário/crescimento & desenvolvimento , Células Cultivadas , Galinhas , Feminino , Imunofluorescência , Ativação Linfocitária , MasculinoRESUMO
Tumors which are induced in chickens by Rous sarcoma virus (RSV) usually grow progressively for several weeks and then regress. pp60src kinase activity was found to be reduced in cultured tumor cells which derived from regressing sarcomas by 60-75% as compared to progressively growing neoplasms. We further found that a cellular pp89 which co-precipitated with pp60src was largely diminished in tumor cells derived from regressing as compared with progressively growing sarcomas. In contrast, immunoprecipitation analyses from membrane or cytosol fractions did not reveal any significant differences between these 2 types of tumor cells in distribution of pp60src. Moreover, partial proteolysis or isoelectric focussing of labelled immunoprecipitated pp60src did not reveal major differences between the 2 tumor cell types. These data indicate that the lack of pp89 cell binding to pp60src in regressing sarcoma cells correlates well with the diminution of the pp60src kinase activity in these cells, but does not affect the transport of pp60src to the plasma membrane.
Assuntos
Galinhas/microbiologia , Regressão Neoplásica Espontânea/enzimologia , Proteínas Proto-Oncogênicas/metabolismo , Sarcoma Aviário/enzimologia , Animais , Regressão Neoplásica Espontânea/metabolismo , Proteínas Proto-Oncogênicas pp60(c-src) , Sarcoma Aviário/metabolismoRESUMO
AIMS: Contributions to the knowledge of some peculiarities of C. difficile involvement in human pathology, nosocomial infections (NI) included. MATERIAL AND METHODS: This clinico-epidemiological and laboratory study included 14 patients admitted to the Medical Clinic of the Iasi Regional Cancer Institute with the diagnosis of C. difficile NI based on detection of toxins A and B in stool samples. The data were assessed and interpreted using an algorithm which revealed the peculiarities of C. difficile NI outbreak occurrence and evolution. RESULTS: Of the 14 cases included in the study, 5 (35.8 %) had community-onset infections and 9 (64.3%) oncology unit-onset infections. The average hospital stay was 22 days. Immunocompromised condition and the use of antibiotics in the ciprofloxacin, colistin and cefotaxime group for 4 - 10 days were the main risk factors. CONCLUSIONS: This epidemic C. difficile NI outbreak which affected immunocompromised patients with high susceptibility to infection, common finding in oncology care was brought under control by active preventive measures associated with concomitant antimicrobial therapy effective in C. difficile infections.
Assuntos
Infecção Hospitalar/diagnóstico , Infecção Hospitalar/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Enterocolite Pseudomembranosa/diagnóstico , Enterocolite Pseudomembranosa/epidemiologia , Unidades Hospitalares/estatística & dados numéricos , Hospedeiro Imunocomprometido , Oncologia , Neoplasias/complicações , Adulto , Idoso , Clostridioides difficile/isolamento & purificação , Infecção Hospitalar/microbiologia , Enterocolite Pseudomembranosa/microbiologia , Enterotoxinas/análise , Fezes/microbiologia , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Romênia/epidemiologiaRESUMO
AIM: To determine the relationship between the characteristics of a group of lung cancer patients, lung cancer surgeries, and the incidence of early and/or late postoperative complications. MATERIAL AND METHODS: The study included a group of 115 lung cancer patients aged 40 to 85 years, 76.5% men, 60.91% living in urban areas, who received surgical treatment in the interval January 2013-August 2014. Data were collected from electronic medical records and survey sheets and processed and interpreted using Pearson correlation index (p-value of 0.05 was considered statistically significant and of <0.005 highly statistically significant), and chi2, y, 1c = 25% tests. All statistical analyses were performed using the SPSS statistical software package version 13.0. RESULTS: Of the 115 patients 7.8% were in the 40-50 years age group and 87.8% in the 51-75 years age group (p < or = 0.001). Most patients were males (76.5%, p < 0.001), and 60.9% of the patients were living in urban areas (p < or = 0.05). The difference in the prevalence of smokers (76.5%) vs. non smokers (23.5%) was highly statistically significant (p < 0.005). Active smoking of one pack of cigarettes per day for more than 10 years was recorded in 54.8%. The presence of co morbidities (17 events) and the distribution of neoplastic lesions in the five anatomical areas required the performance of lobectomies, bilobectomies or pneumectomies. The incidence of early (14 entities) and late postoperative complications (7 entities) depended on patient's general condition, nature of co morbidities, location and stage of neoplastic lesions, and surgical complexity. CONCLUSIONS: Lung cancer, in various locations and stages, most commonly affected males aged 40-85 years, from urban areas, smokers, with various co morbidities. Surgeries performed in these patients were often laborious and with a relatively low incidence of postoperative complications.
Assuntos
Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Complicações Pós-Operatórias , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Humanos , Incidência , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Pneumonectomia/efeitos adversos , Pneumonectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Prevalência , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Romênia/epidemiologia , Resultado do TratamentoRESUMO
AIM: To assess the clinical and epidemiological features of all three main histological types of non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The study included 34 patients with NSCLC admitted to specialized units of the Iasi Regional Cancer Institute (IRCI) in the interval May 2012 - May 2014. Data were collected electronically based on a clinical-epidemiological survey form. The obtained data were then processed and interpreted by statistical-mathematical methods using the correlation index (significant at p < or = 0.05 and highly significant at p < 0.005), chi-square and Y tests. Data were analyzed using SPSS 13.0 (SPSS Inc. Chicago, Illinois, USA). RESULTS: Most NSCLC patients were aged 56-71 years, the Pearson correlation index between age and diagnosis being p = 0.01. Sex difference was highly significant (p = < 0.001) and so was the relationship between heavy smoking and age groups. Most cases were histogenetically classified as adenocarcinomas (22%). Four patients (21%) were in stage IIIA NSCLC, 4 (21%) IIIB, 9 (47.3%) IV, and 15 (79%) unspecified stage. All patients received primary chemotherapy. Single or associated complications included anemia and other hematologic disorders (26-74.6%), respiratory failure, hemoptysis, cachexia, atelectasis, etc. Surgery was performed in 5 (14.7%) stage IIIA NSCLC patients. CONCLUSIONS: NSCLC showed a highly significant predominance in the age groups 56-71 years, and the most common histologic type was adenocarcinoma. All patients received primary chemotherapy, and patients with stage IIIA underwent surgery. Anemia and other hematologic disorders were the most common complications.
Assuntos
Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Adenocarcinoma/terapia , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimioterapia Adjuvante/métodos , Feminino , Inquéritos Epidemiológicos , Humanos , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pneumonectomia/métodos , Fatores de Risco , Romênia/epidemiologia , Fumar/efeitos adversos , Resultado do TratamentoRESUMO
UNLABELLED: Rhabdomyosarcomas (RMS) are the most frequent soft tissue sarcomas of childhood. Despite advances in knowledge about biological pathways of tumorigenesis, risk stratification and multimodal treatment, the immediate and long-term prognosis of these lesions in many countries with limited resources is still poor. PATIENTS AND METHODS: Twenty-five histologically confirmed pediatric RMS were recorded during the period of study. Demography, clinical presentation, diagnostic means, pretreatment staging and post-surgical grouping, histological type, therapy and outcome were evaluated. RESULTS: The mean age was 6.7 years; the group included 12 boys and 13 girls. Twelve lesions were localized in the genitourinary tract, eight in the trunk and extremities, two cases each in head and neck and retroperitoneum and one case in biliary tract. Primary surgical attempt was performed in 15 patients but only in nine of them underwent complete resection (three with free margins) other six cases achieving removal with residual disease. In 10 cases, solely biopsy was possible. Twenty-four patients received chemotherapy but only four cases performed radiation therapy. Overall survival rate was only 36% (nine cases). CONCLUSIONS: As mean feature children from our series had late presentation with locally extended (bulky and node positive) lesions and unfavorable sites. Improved multimodal management of RMS in recent years will probably lead to better survival curves in an increasing number of cases and an outstanding outcome in children with locally advanced disease.
Assuntos
Rabdomiossarcoma/patologia , Rabdomiossarcoma/cirurgia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Rabdomiossarcoma/terapiaRESUMO
UNLABELLED: Single nucleotide polymorphisms (SNPs) of the CYP19A1 gene have shown the ability to modify its activity, but no association has been established with aromatase inhibitor (AI) efficiency in hormone receptor positive breast cancer (BC). MATERIAL AND METHODS: The study included blood samples from 53 patients (p) with BC and 1 control (male DNA); 22p. (investigational group) were administered an Al and followed up. RESULTS: Homozygous (hh) -CC and TT -, and heterozygous (hz) - TC - genotypes of the rs10046 SNP were balanced. Response to treatment or progression were not affected (p=0.630) in patients with T allele 1; local relapse occurred significantly more rarely and overall survival (OS) was superior (p=0.046). For rs4646, genotypes were mainly hhGG (57%), with no implication to study parameters (p>0.05). For rs727479 SNP, major genotypes were hhTT (40%) and hzTG (45%). Therapeutic response was better in patients with T allele 2 (p=0.040), T allele 1 was associated with reduced local recurrence (p=0.047) and TT genotype with better OS (p = 0.008). In rs700518 SNP, genotype was mostly hzGA (49%). Local recurrence rates were reduced in the presence of G allele 1 (p=0.047) and GG homozygosity. CONCLUSIONS: At this stage, the study was purely exploratory and hypothesis generating. Genotyping of at least three of the four CYP19A1 SNPs evaluated (except rs4646) may have an impact in clinical practice, providing better criteria for patient selection, prognosis and therapeutic decision in BC.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Aromatase/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Mutação , Polimorfismo de Nucleotídeo Único , Alelos , Biomarcadores/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Incidência , Masculino , Seleção de Pacientes , Valor Preditivo dos Testes , Prognóstico , Recidiva , Sensibilidade e Especificidade , Taxa de SobrevidaRESUMO
BACKGROUND/OBJECTIVES: The hepatic prognosis of long-term home total parenteral nutrition (TPN)-dependent children is poorly documented. The objective was to study outcome data in home TPN-dependent children and to describe precisely their liver biopsies in the attempt to analyze risk factors for biochemical and histological hepatic abnormalities. SUBJECTS/METHODS: Medical records of 42 children receiving home TPN for more than 2 years between January 1998 and December 2007 in a single approved home total parenteral center were reviewed. Hepatic biochemical abnormalities were analyzed. Hepatic biopsies were classified by two independent pathologists. RESULTS: Duration of TPN was 7.9±0.8 years (mean±s.e.m.), with an average age at onset of 1.5±0.5 years. A total of 24 patients (57%) developed biochemical liver abnormalities in an average of 2.9±0.4 years after starting TPN. Risk factors for biochemical abnormalities were younger age at TPN commencement, longer duration of TPN, higher rate of catheter-related infections and higher volume and energy content of TPN. Liver biopsies were carried out in 43% of patients (mean age 3.2±0.9 years). Almost all patients had fibrosis (94%). Risk factors were dependent on each histological abnormality: fibrosis was significantly associated with a shorter length of bowel and a longer duration of TPN; cholestasis correlated with a lower percentage of total parenteral energy intake due to lipids; and steatosis had no risk factor identified. CONCLUSION: Our study reports a high rate of histological liver abnormalities and analyzes risk factors in children who underwent very long-term home TPN.
Assuntos
Colestase/etiologia , Fígado Gorduroso/etiologia , Cirrose Hepática/etiologia , Nutrição Parenteral Total no Domicílio/efeitos adversos , Fatores Etários , Biópsia , Infecções Relacionadas a Cateter/complicações , Pré-Escolar , Gorduras na Dieta/administração & dosagem , Ingestão de Energia , Feminino , Humanos , Lactente , Intestinos/anatomia & histologia , Lipídeos/administração & dosagem , Fígado/patologia , Cirrose Hepática/epidemiologia , Cirrose Hepática/patologia , Masculino , Prevalência , Prognóstico , Fatores de Risco , Síndrome do Intestino Curto/complicaçõesRESUMO
AIM: Changing the sequence of therapeutic options in stage II breast cancer: first, a core biopsy, followed by the evaluation of the tumoral markers, adaptation of the chemotherapy scheme and finally, surgical approach. Thus would be possible to improve the hope of life in some stage II breast cancer patients, in whom survival is poorer than in some stage III patients. MATERIAL AND METHOD: 144 patients in stage II breast cancer were included in this study, over a period of 5 years (2000-2004). In all these patients the first therapeutic option was surgery (radically modified mastectomy type Madden), followed by systemic chemotherapy-FAC or FEC, 6 cycles, and finally Tamoxifen. RESULTS: 34 out of them developed metastases in a period between 6 and 72 months, most of them in the first 26 months; 25 out of these 34 didn't have metastases in the axillary lymph nodes, and in 18 patients estrogen--and progesterone--receptors were highly positive. HER 2 neu was negative or low expressed in patients with metastases. CD 34 wasn't evaluate in the whole group. CONCLUSIONS: Early onset of metastases in the studied patients, in whom tumoral aggressiveness markers were not obvious, impose the evaluation of the angiogenesis markers and, when positive, chemotherapy as the first therapeutic option.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/terapia , Mastectomia Radical Modificada , Recidiva Local de Neoplasia/terapia , Tamoxifeno/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biópsia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Transformação Celular Neoplásica , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
UNLABELLED: The aim of this study is to point out the late diagnosis and initiation of treatment in male with breast cancer. At the same time, to show the importance of the correlation between different markers in assessing the prognostic, as well as the treatment for the patient. MATERIAL AND METHODS: Retrospective study on a group of 15 males with breast cancer, out of 1043 patients with the disease, in a period of 10 years. Eight patients were stage III of disease, 2 were stage II, one was stage I, and in other 3 cases the evaluation of the tumor and of the axillary lymph nodes was performed only by echography, considered stage II. RESULTS: All patients underwent radically modified Madden mastectomy; 4 patients needed a partial resection of the great pectoralis muscle. Adjuvant chemotherapy was performed in 9 patients, and neoadjuvant chemotherapy in 2 cases. Three patients refused the chemotherapy, and one patient chose an alternative paramedical treatment. The treatment with Tamoxifen was done in 11 patients with high values of Progesterone and Estrogen Receptors (PR, ER). At the date of our study, 8 patients were alive, without clinical signs of disease (free of disease), while in 3 patients, alive, clinical signs of disease were detected (recurrence). Survival rate couldn't be evaluated in 4 patients. CONCLUSIONS: Breast cancer in male is usually discovered in locally advanced stages, although most of the patients are regularly screened for chronic hepatitis. Use of biological markers allows a more accurate evaluation of the aggressiveness of the tumor, as well as a more specific treatment for each patient. Modified radical mastectomy type Madden remains the preferred surgical approach. Surgical approach should be considered even in locally advanced cases, as well as in elder patients.
Assuntos
Neoplasias da Mama Masculina/patologia , Neoplasias da Mama Masculina/cirurgia , Carcinoma/patologia , Carcinoma/cirurgia , Mastectomia Radical Modificada , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/uso terapêutico , Biomarcadores Tumorais/sangue , Neoplasias da Mama Masculina/sangue , Neoplasias da Mama Masculina/tratamento farmacológico , Neoplasias da Mama Masculina/mortalidade , Carcinoma/sangue , Carcinoma/tratamento farmacológico , Carcinoma/mortalidade , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Quimioterapia Adjuvante , Diagnóstico Tardio , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Receptores de Estrogênio/sangue , Receptores de Progesterona/sangue , Estudos Retrospectivos , Análise de Sobrevida , Tamoxifeno/uso terapêutico , Resultado do TratamentoRESUMO
In autumn 2011 in cyprinid farms located in Iasi on the Jijia river, several infections with bacterial strains and macroscopical external cysts on the skin were diagnosedwhich developed as a result of the stress induced by biotic and abiotic factors. On the examination of the cyst contents the presence of numerous spores was observed, mostly of the Dermocystidium sp genusThe samples were taken from the common carp (Cyprinus carpio) and crucian carp (Carassius auratus gibelio) species from the fish farm as well as from the Jijia River. 35 fish were examined, all of them showing cysts, fragmentation of their dorsal fin and congestion of the gills. Histological examination of the skin showed a field of multiple dermal cysts with round light eosinophilic formations (14-16µm) containing a central refractable body similar to that reported for Dermocystidium sp. Gills samples were taken from the affected areas for the SEM examination with the purpose of evaluating not only aspects of normal morphology, but also aspects of some modifications of the affected areas as well as the presence of the etiologically incriminated bacteria Pseudomonas fluorescens. The isolates were identified through phenotypic methods. All the strains that showed mobility and oxidase-positivity were tested using API 20 NE strip. Consequently, they were taxonomically grouped into the species Pseudomonas fluorescens. The scanning electron microscope (SEM) was used for the first time in the characterization of the bacterial lesions produced by Pseudomonas strains on Cyprinus carpio and Carassius auratus gibelio gills. The diagnosis of septicemia with conditional pathogen species of Pseudomonas fluorescens was correlated with the results of the physico-chemical investigations of water and the data concerning the breeding conditions of the investigated livestock.(AU)
No outono de 2011, em fazendas de ciprinídeos localizadas em Iasi, no rio Jijia, diversas infecções bacterianas e cistos externos macroscópicos na pele se desenvolveram como resultado do estresse induzido por fatores bióticos e abióticos. No exame do conteúdo dos cistos, a presença de diversos esporos foi observada, a maioria do gênero Dermocystidium sp. As amostras foram colhidas das seguintes espécies: carpa comum (Cyprinus carpio) e carpa cruciana (Carassius auratus gibelio) de fazenda piscícola, além do rio Jijia. Assim sendo, 35 peixes foram examinados, todos demonstrando cistos, fragmentação da barbatana dorsal e congestão das guelras. O exame histológico da pele mostrou um campo de múltiplos cistos dérmicos com formações circulares claras eosinofílicas (14-16µm) contendo corpo central refratado similar ao relatado para Dermocystidium sp. Amostras de guelras foram retiradas das áreas afetadas para exame MEV, com o propósito de se avaliar não apenas os aspectos da morfologia normal, mas também os aspectos de algumas modificações das áreas afetadas, além da presença da bactéria etiologicamente incriminada: Pseudomonas fluorescens. Os isolados foram identificados por meio de métodos fenotípicos. Todas as amostras que mostraram mobilidade e positividade-oxidase foram testadas usando-se fita API 20 NE. Consequentemente, estas foram taxonomicamente agrupadas na espécie Pseudomonas fluorescens. O microscópio eletrônico de varredura (MEV) foi usado pela primeira vez na caracterização de lesões bacterianas produzidas por Pseudomonas nas guelras de Cyprinus carpio e Carassius auratus gibelio. O diagnóstico de septicemia com espécies condicionais de patogênico de Pseudomonas fluorescens foi correlacionado com os resultados das investigações físico-químicas da água e de dados sobre as condições de reprodução dos animais investigados.(AU)
Assuntos
Animais , Carpas/microbiologia , Carpas/parasitologia , Infecções Bacterianas/veterinária , Doenças Parasitárias em Animais , Dermocidinas , Pseudomonas fluorescens/isolamento & purificação , Fatores Bióticos , Fatores AbióticosRESUMO
In autumn 2011 in cyprinid farms located in Iasi on the Jijia river, several infections with bacterial strains and macroscopical external cysts on the skin were diagnosedwhich developed as a result of the stress induced by biotic and abiotic factors. On the examination of the cyst contents the presence of numerous spores was observed, mostly of the Dermocystidium sp genusThe samples were taken from the common carp (Cyprinus carpio) and crucian carp (Carassius auratus gibelio) species from the fish farm as well as from the Jijia River. 35 fish were examined, all of them showing cysts, fragmentation of their dorsal fin and congestion of the gills. Histological examination of the skin showed a field of multiple dermal cysts with round light eosinophilic formations (14-16µm) containing a central refractable body similar to that reported for Dermocystidium sp. Gills samples were taken from the affected areas for the SEM examination with the purpose of evaluating not only aspects of normal morphology, but also aspects of some modifications of the affected areas as well as the presence of the etiologically incriminated bacteria Pseudomonas fluorescens. The isolates were identified through phenotypic methods. All the strains that showed mobility and oxidase-positivity were tested using API 20 NE strip. Consequently, they were taxonomically grouped into the species Pseudomonas fluorescens. The scanning electron microscope (SEM) was used for the first time in the characterization of the bacterial lesions produced by Pseudomonas strains on Cyprinus carpio and Carassius auratus gibelio gills. The diagnosis of septicemia with conditional pathogen species of Pseudomonas fluorescens was correlated with the results of the physico-chemical investigations of water and the data concerning the breeding conditions of the investigated livestock...
No outono de 2011, em fazendas de ciprinídeos localizadas em Iasi, no rio Jijia, diversas infecções bacterianas e cistos externos macroscópicos na pele se desenvolveram como resultado do estresse induzido por fatores bióticos e abióticos. No exame do conteúdo dos cistos, a presença de diversos esporos foi observada, a maioria do gênero Dermocystidium sp. As amostras foram colhidas das seguintes espécies: carpa comum (Cyprinus carpio) e carpa cruciana (Carassius auratus gibelio) de fazenda piscícola, além do rio Jijia. Assim sendo, 35 peixes foram examinados, todos demonstrando cistos, fragmentação da barbatana dorsal e congestão das guelras. O exame histológico da pele mostrou um campo de múltiplos cistos dérmicos com formações circulares claras eosinofílicas (14-16µm) contendo corpo central refratado similar ao relatado para Dermocystidium sp. Amostras de guelras foram retiradas das áreas afetadas para exame MEV, com o propósito de se avaliar não apenas os aspectos da morfologia normal, mas também os aspectos de algumas modificações das áreas afetadas, além da presença da bactéria etiologicamente incriminada: Pseudomonas fluorescens. Os isolados foram identificados por meio de métodos fenotípicos. Todas as amostras que mostraram mobilidade e positividade-oxidase foram testadas usando-se fita API 20 NE. Consequentemente, estas foram taxonomicamente agrupadas na espécie Pseudomonas fluorescens. O microscópio eletrônico de varredura (MEV) foi usado pela primeira vez na caracterização de lesões bacterianas produzidas por Pseudomonas nas guelras de Cyprinus carpio e Carassius auratus gibelio. O diagnóstico de septicemia com espécies condicionais de patogênico de Pseudomonas fluorescens foi correlacionado com os resultados das investigações físico-químicas da água e de dados sobre as condições de reprodução dos animais investigados...