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1.
Pharmacogenomics J ; 20(2): 350, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30659276

RESUMO

In the abstract and in other parts of the manuscript the authors wrote that the mutation rs396991 causes a valine (V) to phenylalanine (F) substitution at position 157. However, the correct codon number is 158. These errors have not been fixed in the original Article.

2.
Pharmacogenomics J ; 18(3): 474-479, 2018 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-28719596

RESUMO

FCGR2A-H131R and FCGR3A-V157F are single-nucleotide polymorphisms known to influence the outcome of patients treated with rituximab, cetuximab and trastuzumab. We investigated the impact of these polymorphisms on the clinical outcome of 103 patients with recurrent or metastatic squamous cell carcinoma of the head and neck treated with a platinum compound, fluorouracil and cetuximab as palliative first-line therapy. The survival of patients with FCGR2A-131H/H and/or FCGR3A-157V/V genotypes was significantly longer compared with patients carrying 131R and 157F alleles (median progression-free survival (PFS): 5.5 vs 4.1 months, P=0.02; median overall survival: 10.2 vs 7.2 months, P=0.04). In multivariate analysis, the FCGR2A and 3A genotypes as well as the time between initial diagnosis and relapse of disease not amenable to curative therapy remained the only independent prognostic factors for PFS. The results are in line with previous reports in colorectal cancer patients and confirm the possible value of genetic polymorphisms of immunocompetent cells for the success of cetuximab treatment.


Assuntos
Recidiva Local de Neoplasia/tratamento farmacológico , Receptores de IgG/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Adulto , Idoso , Cetuximab/efeitos adversos , Cetuximab/genética , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Polimorfismo de Nucleotídeo Único/genética , Intervalo Livre de Progressão , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
3.
Pharmacogenomics J ; 17(4): 344-350, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-27139155

RESUMO

Biomarkers for bevacizumab efficacy in metastatic breast cancer (MBC) are of urgent need. The genetic variability of genes involved in angiogenesis could explain the interpatient variability of drug effects. For this biomarker study DNA was extracted from tumor blocks or blood samples of patients with human epidermal growth factor receptor 2 (HER2)-negative MBC treated with bevacizumab in combination with chemotherapy (bevacizumab cohort, 163 patients) or chemotherapy only (control cohort, 105 patients). We assessed the correlation of 10 single-nucleotide polymorphisms (SNPs) in genes modulating angiogenesis (vascular endothelial growth factor-A (VEGF-A), VEGF receptor 1 (VEGFR-1), serine threonine kinase 39 (STK39)) or hypertension (endothelin-1 and uromodulin) with outcome and toxicity. In the bevacizumab cohort, the SNP rs5370-TT in endothelin-1 (EDN1) showed a significantly shorter median overall survival (OS, 6.3 vs 21.3 months; hazard ratio (HR) 2.89, 95% confidence interval (CI) 1.34-6.26; log-rank P=0.0069) and a trend toward worse median progression-free survival (3.5 vs 7.9 months; HR 2.05, 95% CI 0.96-4.39; log-rank P=0.065) compared with the alternate genotypes combined. Similarly, patients harboring the VEGF-936 (rs3025039) TT alleles showed a significantly shorter median OS than patients with VEGF-936 CC or CT (14.9 vs 21.3 months; HR 2.37, 95% CI 1.09-5.13; P=0.0286). In multivariate analysis including important clinical parameters like disease-free survival (DFS), adjuvant chemotherapy, ECOG (Eastern Cooperative Oncology Group) performance score, histologic subtype, grade, hormone receptor status, visceral metastases and treatment line, only the association of rs5370 (EDN1) with OS was still statistically significant (P=0.012). In the control cohort, no association of the EDN1 genotype with outcome was seen, suggesting a predictive value for bevacizumab. In conclusion, the SNP rs5370 in endothelin-1 could help identifying patients who unlikely gain any benefit from bevacizumab.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Bevacizumab/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Endotelina-1/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/genética , Receptor ErbB-2/genética , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética
4.
Ann Oncol ; 25(1): 171-6, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24299961

RESUMO

BACKGROUND: Obesity is a well-known risk factor for the development of several types of cancer including lymphomas, but its influence on the course of disease is fairly unknown. Recently, a retrospective cancer registry analysis demonstrated significantly prolonged survival for overweight and obese patients with diffuse large B-cell lymphoma (DLBCL). The study population almost exclusively consisted of male US American patients of lower socioeconomic status and one-fifth of patients received cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) chemotherapy without rituximab. Therefore, it remains unclear if these results can be extrapolated to the general DLBCL population. PATIENTS AND METHODS: This retrospective single-center analysis included 183 unselected DLBCL patients who were treated with rituximab and standard-dosed anthracycline-based chemoimmunotherapy as first-line therapy between January 2004 and December 2012. Patients were stratified by body mass index (BMI) into 'low BMI' (<25.0 kg/m(2)) and 'high BMI' (≥25.0 kg/m(2)). RESULTS: The two groups were well balanced regarding age, performance score, international prognostic index, B-symptoms and extranodal involvement. However, there was a trend for male sex (P = 0.053) and higher-stage disease (P = 0.066) in the high-BMI group. Patients with higher BMI had significantly longer overall survival (OS; hazard ratio [HR] 0.546; P = 0.035) with 80.9% of patients alive at 3 years versus 64.2% in the low-BMI group. BMI was also an independent prognostic factor for OS in multivariate analysis (HR 0.557; P = 0.043). CONCLUSION: We could show a significant association between overweight/obesity and improved OS in an unselected DLBCL cohort.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Índice de Massa Corporal , Estudos de Coortes , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Prednisona/administração & dosagem , Modelos de Riscos Proporcionais , Rituximab , Resultado do Tratamento , Vincristina/administração & dosagem , Adulto Jovem
5.
Klin Monbl Augenheilkd ; 225(2): 151-4, 2008 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-18293267

RESUMO

BACKGROUND: The aim of this study was to compare central corneal thickness (CCT) and intraocular pressure in patients participating in a glaucoma screening programme and patients who were examined in the glaucoma unit. MATERIALS AND METHODS: 406 patients of a glaucoma screening programme (Salzburg-Moorfields collaborative glaucoma study) were included in this study. In addition a group of 406 patients who were admitted to the glaucoma clinic for a detailed glaucoma examination was included (outpatient clinic group). In all participants central corneal thickness (CCT) was measured and possible relations of CCT within the study groups were statistically analysed. RESULTS: In the population screening group the mean central corneal thickness in normal subjects was 536+/-4.3 microm, in patients with ocular hypertension (OHT) 552+/-5.7 microm, patients suffering from a normal tension glaucoma (NTG) showed a mean CCT of 534+/-14.2 microm and those with primary open angle glaucoma (POAG) had a value of 521+/-17.9 microm. In the 'outpatient clinic group' the OHT subgroup had a mean CCT of 553+/-6.8 microm, the NTG subgroup of 529+/-26.5 microm and the one with POAG had a mean of 527+/-19.8 microm. In addition, CCT was measured in all glaucoma patients whose "partner" eye was healthy (544+/-5 microm) and included in this study as part of the normal subgroup. In both groups (screening group and outpatient group), CCT was significantly higher in OHT patients than in normals. In contrast, no statistically significant difference between normals and NTG or POAG patients was detected. Intraocular pressure was significantly lower in the screening groups than in the other ones. CONCLUSIONS: Our data confirm the previously published results concerning OHT and healthy subjects. In this study no significant difference between NTG or POAG subjects and normal eyes was detected. The lower IOP in the screening population can be explained by the fact that patients contacting the screening program are self selected whereas patients of the glaucoma unit are admitted by practising ophthalmologists and are, therefore, rather advanced cases or carrying special risk factors.


Assuntos
Instituições de Assistência Ambulatorial , Córnea/patologia , Glaucoma de Ângulo Aberto/diagnóstico , Pressão Intraocular/fisiologia , Programas de Rastreamento , Hipertensão Ocular/diagnóstico , Oftalmologia , Áustria , Humanos , Manometria , Variações Dependentes do Observador , Oftalmoscopia , Valores de Referência , Ultrassonografia , Testes de Campo Visual
6.
Klin Monbl Augenheilkd ; 222(12): 1002-7, 2005 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-16380886

RESUMO

BACKGROUND: Central visual field defects due to glaucoma are common, increasing with old age. Impaired visual processing, for instance caused by glaucoma, may play a role in the aetiology of car accidents involving older drivers which can result in personal injury. Mandatory eye exams with assessment of the visual field in elderly people holding a driving licence will become more and more important, especially in a continuously ageing and increasingly mobile population. MATERIALS AND METHODS: In this prospective study, 80 patients with overt glaucoma and 52 patients without glaucoma, all holders of a valid driving licence, were enrolled. For each patient, the best corrected visual acuity was recorded and an examination of the central visual field was performed with automatic perimetry. In addition, a detailed questionnaire about the current driving habits of the patient was requested. RESULTS: In summary, 29 patients (36 %; 95 % CI: 26 - 48 %) of 80 glaucoma patients were driving a motor vehicle with binocular congruent scotomata within the central 30 degrees visual field, which is not sufficient to meet current legal requirements in Austria. In addition, 3 out of 29 impaired patients had a visual acuity that was below the mandatory legal requirements. A total of 39 patients (49 %; 95 % CI: 37 - 60 %) of the glaucoma patients fulfilled legal requirements. Examination of these patients showed only monocular or binocular central visual field defects that were not congruent. However, 12 (15 %; 95 % CI: 8 - 25 %) patients were holders of a valid driving licence, but had stopped driving some time ago. Based on the prevalence of glaucoma and the number of driving licence holders, the projected number of actively driving glaucoma patients who do not meet the legal requirements regarding the visual field is probably around 15,400 (7,400 - 29,500) in Austria and around 163,500 (79,000 - 313,500) in Germany. CONCLUSIONS: Time limits for the validity of the driving licence within the European Community have been set. In addition, the legal requirements for driving a motor vehicle should also be clearly defined, especially the requirements regarding the visual field and the acceptable dimensions of central scotomata. In addition, a mandatory eye exam for older drivers to be performed by ophthalmologists should be considered in order to detect persons posing a safety risk in traffic.


Assuntos
Exame para Habilitação de Motoristas/estatística & dados numéricos , Condução de Veículo/estatística & dados numéricos , Condução de Veículo/normas , Glaucoma/epidemiologia , Hábitos , Medição de Risco/métodos , Transtornos da Visão/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Áustria/epidemiologia , Exame para Habilitação de Motoristas/legislação & jurisprudência , Condução de Veículo/legislação & jurisprudência , Comorbidade , União Europeia , Feminino , Fidelidade a Diretrizes/legislação & jurisprudência , Fidelidade a Diretrizes/normas , Fidelidade a Diretrizes/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Distribuição por Sexo , Inquéritos e Questionários , Acuidade Visual
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