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1.
Dig Dis ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38569478

RESUMO

INTRODUCTION: CFTR modulator therapy improves nutritional status and quality of life. Clinical trials have shown pancreatic insufficiency conversion, mostly in pediatric patients treated with ivacaftor. Studies with elexacaftor/tezacaftor/ivacaftor (ETI) in older patients have not suggested restoration of exocrine pancreas function, but quality data in adults are lacking. Our aim was to show the effect of ETI in adults with CF on nutritional status and digestive function. We hypothesized improvement of nutritional parameters and gastrointestinal symptoms, reduction of pancreatic enzyme replacement therapy, but uncertain improvement in exocrine pancreatic function. METHODS: We prospectively enrolled adults with CF treated with ETI from August 2021 to June 2022. We measured anthropometric parameters, laboratory nutritional markers, change of fecal elastase, pancreatic enzymes replacement therapy needs, and gastrointestinal symptoms. RESULTS: In the cohort of 29 patients (mean age 29.1 years), 82.8% suffered exocrine pancreatic insufficiency. After ETI, mean BMI increased by 1.20 kg/m2 (p < 0.001), mean body weight by 3.51 kg (p < 0.001), albumin by 2.81 g/L, and prealbumin by 0.06 (both p < 0.001). Only one patient, initially pancreatic insufficient (4.5%, p < 0.001), developed pancreatic sufficiency, indicated by increased fecal elastase from 45 µg/g to 442.1 µg/g. Mean change in lipase substitution decreased by 1,969 units/kg/day (p < 0.001) and stools frequency by 1.18 per day (p < 0.001). CONCLUSION: Our data suggest increased nutritional parameters, lower pancreatic substitution requirements, and improved defecation in adult CF patients on ETI. Improvement in exocrine pancreatic function might be mutation-specific and needs further study.

2.
J Cancer Res Clin Oncol ; 149(19): 17123-17131, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37768380

RESUMO

PURPOSE: The aim of our study was to evaluate if therapeutic success in the first-line of anticancer treatments in patients with NSCLC may predict treatment success in the following lines. METHODS: We analyzed the data of patients with NSCLC stage III/IV from the TULUNG registry separately for chemotherapy, TKIs, ALK inhibitors, and immunotherapy in the first line during the years 2011-2019. "Succesful treatment " was defined as PFS ≥ 6 months, a "good responder " was a patient with ˃50% of "successful treatment " lines. Treatment responses were analyzed separately for each drug group. Descriptive statistics, Fisher exact test, Pearson Chi-Squared test, log-rank test, and univariate/multivariate logistic regression models were used. RESULTS: The first-line TKI therapy was successful in 66.2%, while good responders accounted for 50.7% of the cohort and their rates were similar for all types of TKIs. First-line platinum-based chemotherapy was successful in 43.1% and 48.6% for combinations with pemetrexed and bevacizumab, respectively. Good responders accounted for 29.5% and 25.9%, respectively. In the group of ALK inhibitors, we observed treatment success in 52.3% of cases, while alectinib showed the highest effectiveness (up to 70%). Good responders constituted 50% of the group. In the first-line immunotherapy group, survival benefit was observed in 52.3%, and good responders constituted 52.3% of the cohort. CONCLUSION: We concluded that the treatment success in first-line therapies in patients with NSCLC may predict survival benefits in the subsequent lines, particularly in EGFR- or ALK-positive disease and immunotherapy-treated patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Pemetrexede/uso terapêutico , Bevacizumab/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Receptores ErbB
3.
Anal Chem ; 94(18): 6736-6744, 2022 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-35471013

RESUMO

Alterations in oligosaccharides and types of sialic acid (SA) attachments have been associated with different pathological states. Matrix-assisted laser desorption mass spectrometry (MS) is commonly used for glycosylation studies. However, native sialylated glycans are suppressed or not detected during MS experiments. Consequently, different approaches have been employed to neutralize the negative charge of the carboxyl group. In this study, we present the advantage of phenylhydrazine (PHN) labeling for the detection and efficient discrimination of SA linkages when this derivatization follows alkyl esterification. As expected, PHN-labeled sialylated oligosaccharides with the 2,6-linkage type can be easily recognized according to the additional shift in mass corresponding to the presence of a methyl or ethyl group. Surprisingly, oligosaccharides with the 2,3-linked SA residue instead of a lactone were detected carrying the second PHN unit. This was beneficial as no further processing after esterification was needed to stabilize the lactone form. Moreover, during tandem mass experiments, all modified glycans produced favorable fragmentation patterns with a coherent recognition of SA linkages. Although both types of esterification, herein called the EST-PHN approach, provided comparable results, methylation exhibited marginally higher linkage specificity than ethyl esterification. The simplicity and effectiveness of the methodology are demonstrated on the model compound, sialyllactose, and its applicability for biological studies is presented on N-glycan profiling in the sera of lung cancer patients.


Assuntos
Neoplasias Pulmonares , Oligossacarídeos , Esterificação , Humanos , Lactonas , Neoplasias Pulmonares/diagnóstico , Ácido N-Acetilneuramínico/química , Oligossacarídeos/química , Fenil-Hidrazinas/química , Polissacarídeos/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
4.
Cancer Diagn Progn ; 2(2): 167-172, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35399169

RESUMO

Background/Aim: This study aimed at contributing to a better diagnosis of lung cancer by analyzing the patient's symptoms and their linkage to other characteristics. Patients and Methods: We analyzed the data of 3,322 patients from LUCAS (LUngCAncerfocuS) National Registry of the Czech Republic. Overall survival was assessed using the Kaplan-Meier method. Results: The most common symptoms were cough (47.5%), dyspnea (45.6%), pain (27.3%), and weight loss (25.7%). Among all patients, 16% were asymptomatic. We demonstrated the negative prognostic significance of increasing number of lung cancer symptoms, that was significant after adjustment for age, TNM stages, and performance status, and morphological types of the cancer. Conclusion: Monitoring the severity and type of symptoms in patients with lung cancer can help in the diagnostics of the disease and the estimation of prognosis.

5.
Anticancer Res ; 41(11): 5549-5556, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34732425

RESUMO

BACKGROUND/AIM: LUCAS is a clinical lung cancer registry (ClinicalTrials.gov identifier is NCT04228237), prospectively collecting data from newly diagnosed lung cancer patients in seven pneumooncology centers in the Czech Republic, since June 1, 2018. The aim of the study was to assess the stage of the disease at the time of diagnosis, percentage of morphological types, survival, percentage of driving mutations, eligibility for radical surgery, and percentage of patients who undergo radical surgery, in the non-smoking population in comparison with smokers and former smokers. PATIENTS AND METHODS: The total number of patients in the registry at the time of the analysis was 2,743. Only 2,439 patients with complete records (smoking status, stage, and type of tumor) were included in this study. RESULTS: The analysis indicated that non-smokers are diagnosed at a later stage of the disease but they have a better survival rate than smokers. Fewer smokers with stage III disease who are eligible for radical surgery will undergo surgery compared to non-smokers with the same clinical stage. Driving mutations are more common in non-smokers, even after adjustment for the more frequent occurrence of adenocarcinoma in the group of non-smokers. CONCLUSION: The data from LUCAS registry are consistent with already known facts, suggesting that the LUCAS registry is a useful clinical tool.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Neoplasias Pulmonares/epidemiologia , não Fumantes , Carcinoma de Pequenas Células do Pulmão/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , República Tcheca/epidemiologia , Ex-Fumantes , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Pneumonectomia , Estudos Prospectivos , Sistema de Registros , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/terapia , Fumantes , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
6.
Anticancer Res ; 41(11): 5625-5634, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34732435

RESUMO

BACKGROUND/AIM: Per literature, patients with epidermal growth factor receptor (EGFR) exon-20 insertions respond poorly to tyrosine kinase inhibitors (TKIs). This study analyzed real-world data to examine the prognostic and predictive value of these mutations. PATIENTS AND METHODS: We conducted a retrospective cohort study using Czech TULUNG Registry data, with data on multiple mutation types, collected in 2011-2020. RESULTS: We analyzed 554 (95.85%) patients with EGFR exon-19 deletions or exon-21 L858R substitutions and 24 (4.15%) patients with exon-20 insertions who received first-line high-value therapies. We summarized clinical characteristics and outcomes in all patients and by cohort. The risk of progression was statistically significantly higher (86%) in the exon-20 insertion cohort compared to the cohort with other mutations. Although not statistically significant, the risk of death was 44% higher in patients with exon-20 insertions. CONCLUSION: Advanced NSCLC patients with rare EGFR exon-20 insertions have a high risk of progression.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Mutagênese Insercional , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , República Tcheca , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/genética , Éxons , Feminino , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Inibidores de Proteínas Quinases/uso terapêutico , Sistema de Registros , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
7.
Cancer Treat Res Commun ; 28: 100427, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34284344

RESUMO

PURPOSE: To investigate the efficacy and safety of an active cellular immunotherapy (DCVAC/LuCa) and chemotherapy in patients with stage IV non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: SLU01 was a multicenter, open-label, parallel-group, randomized, phase I/II trial. NSCLC patients were randomized in a ratio of 1:1:1 to receive: DCVAC/LuCa and chemotherapy (carboplatin and paclitaxel; Group A); DCVAC/LuCa, chemotherapy, pegylated interferon-α2b, and hydroxychloroquine (Group B); or chemotherapy alone (Group C). DCVAC/LuCa was administered subcutaneously every 3-6 weeks (up to 15 doses). The primary endpoint was overall survival (OS). During the study, enrollment into Group B was discontinued for strategic reasons. RESULTS: Forty-five patients were randomized to Group A, 29 patients to Group B, and 38 patients to Group C. The median OS in the modified intention-to-treat (mITT) population was 3.7 months longer in Group A than in Group C (15.5 vs. 11.8 months; p = 0.0179; hazard ratio = 0.54; 95% confidence interval: 0.32-0.91). This OS effect was consistent across subgroups of the mITT population (females, males, current smokers, former smokers, and patients with non-squamous and squamous cell histology). The most common treatment-emergent adverse events of any grade reported in Groups A, B, and C, respectively, were neutropenia (50.0%, 29.6%, and 20.6%), fatigue (40.0%, 18.5%, and 20.6%), anemia (35.0%, 44.4%, and 32.4%), paresthesia (27.5%, 25.9%, and 17.6%), and alopecia (25.0%, 29.6%, and 41.2%). CONCLUSION: DCVAC/LuCa in combination with carboplatin and paclitaxel extended OS and was well tolerated.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Células Dendríticas/metabolismo , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carboplatina/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/farmacologia , Adulto Jovem
8.
Anticancer Res ; 41(5): 2597-2603, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33952489

RESUMO

BACKGROUND/AIM: Platinum-based chemotherapy with pemetrexed or paclitaxel/bevacizumab are regimens used in combination with checkpoint inhibitors in non-squamous non-small cell lung cancer (NSCLC) treatment. We conducted a real-world study to compare the outcomes of these chemotherapeutic regimens. PATIENTS AND METHODS: We investigated 1,534 patients with advanced non-squamous NSCLC treated with platin/pemetrexed (n=1212) or platin/paclitaxel/bevacizumab (n=322) in 9 cancer centres in the Czech Republic. RESULTS: The regimen containing platin/paclitaxel/bevacizumab showed significantly better overall response rate (ORR) compared to the platin/pemetrexed [40.8% vs. 32.7% (p=0.008)] in the overall population and [55.0% vs. 38.8% (p=0.002)] in the Eastern Cooperative Oncology Group performance status 0 group. There was no significant improvement in progression-free survival (PFS) and overall survival (OS) in either of these two groups of patients. CONCLUSION: In our real-world data analysis, patients treated with platin/paclitaxel/bevacizumab had better overall response rate (ORR), but not PFS or OS. Thus, both treatment regimens are similarly effective. Their selection should therefore be based on the potential side effects.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Pemetrexede/administração & dosagem , Pemetrexede/efeitos adversos , Intervalo Livre de Progressão
9.
Anticancer Res ; 41(4): 2059-2065, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33813414

RESUMO

BACKGROUND/AIM: We investigated efficacy differences for afatinib versus gefitinib in non-small-cell lung cancer (NSCLC) according to epidermal growth factor receptor (EGFR) mutations. PATIENTS AND METHODS: We retrospectively analysed data for 343 patients with NSCLC with performance status 1 having EGFR mutations treated with gefitinib or afatinib. Overall response rate (ORR) was tested by Fisher's exact test. Overall (OS) and progression-free (PFS) survival were estimated by Kaplan-Meier method. RESULTS: ORR did not differ in any group or subgroup. Among all patients, we observed significantly longer PFS for those treated with afatinib vs. gefitinib (median 13.4 vs. 9.5 months, p=0.026), but only a nonsignificant trend was observed for OS. We showed nonsignificant trends of better PFS and OS using afatinib for exon 19 deletion and L858R subgroups. We observed no significant PFS differences for other EGFR mutations but a nonsignificant trend towards better OS for those treated with afatinib. CONCLUSION: Afatinib led to longer PFS for patients with common EGFR mutations but not for those with rare mutations.


Assuntos
Afatinib/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Gefitinibe/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , República Tcheca/epidemiologia , Progressão da Doença , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
10.
Thorac Cancer ; 11(11): 3346-3356, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33016001

RESUMO

BACKGROUND: Data regarding real-life effectiveness of any treatment may improve clinical decision-making. The aim of this study was to evaluate real-life effectiveness of tyrosin-kinase inhibitors, bevacizumab and pemetrexed as first-line treatments in patients with advanced/metastatic non-small cell lung cancer (NSCLC). METHODS: We analyzed data of 2157 patients of the Czech TULUNG Registry of patients with advanced/metastatic NSCLC who received modern-era treatments between 2011 and 2018. Patients treated with gefitinib, erlotinib, afatinib, bevacizumab (+ maintenance), pemetrexed (+ maintenance) as first-line therapy were included in the study. A systematic literature search separately identified clinical trials suitable for calculation of comparator pooled OS and PFS for each regimen. For each subgroup, basic characteristics and survival data (Kaplan-Meier estimates) are shown. We propose the "index of real-life effectiveness" (IRE), a ratio of real-life OS/PFS and comparator pooled OS/PFS. Univariate and multivariate logistic regression identified factors were associated with longer OS (ie, IRE>1.1). RESULTS: Survival analysis showed median OS of 23 months for erlotinib, 29.3 months for afatinib, 19.6 months for gefitinib, 12.2 months for pemetrexed, 17.5 months for pemetrexed maintenance, 15.8 months for bevacizumab and 15.8 months for bevacizumab maintenance. Calculated IREs for OS for the regimens were: erlotinib 1.013, afatinib 1.184, gefitinib 0.736, pemetrexed 1.188, pemetrexed maintenance 1.294, bevacizumab 1.178, and bevacizumab maintenance 1.189. Multivariate regression analysis showed that these factors were associated with longer OS: lower PS for afatinib; lower PS, absence of adverse events and female sex for bevacizumab; and lower PS and female sex for pemetrexed. CONCLUSIONS: This study clearly demonstrated that real-life effectiveness of certain treatment regimens may strongly differ in various populations/health care systems, and comparison between TULUNG data and pooled survival data from trials showed higher real-life effectiveness for most of the studied first-line regimens. Lower ECOG PS, younger age, female sex and adverse events were associated with longer survival in most regimens. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Comparison between TULUNG data and pooled survival data from trials showed higher real-life effectiveness for most of the studied first-line regimens; for most regimens, lower ECOG PS, younger age, female sex and adverse events were associated with longer survival. WHAT THIS STUDY ADDS: Real-life effectiveness of certain treatment regimens may strongly differ in various populations/health care systems.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , República Tcheca , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Sistema de Registros , Análise de Sobrevida
11.
Anticancer Res ; 40(4): 2209-2217, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234916

RESUMO

AIM: To investigate potential association between administration of corticosteroids, antibiotics, probiotics, proton pump inhibitors, non-steroidal anti-inflammatory drugs (NSAID), statins and metformin and outcome in patients with non-small cell lung cancer (NSCLC) treated with nivolumab. PATIENTS AND METHODS: A total of 224 patients with advanced NSCLC treated at nine comprehensive cancer centers were analyzed in this national retrospective study. Survival statistics were evaluated using Kaplan-Meier method and Cox analysis. RESULTS: Only corticosteroid use had a significant negative effect on the objective response rate. In the univariate analysis, there was no significant effect of the studied concomitant medications on the efficacy of nivolumab. In a subsequent multifactorial analysis, a possible positive effect of the concomitant use of NSAID at the initiation of nivolumab treatment was revealed. CONCLUSION: The results of the present retrospective exploratory analysis underscore the importance of knowing the exact type of concomitant medication, the route of administration, the dose of medication, and the region of the ongoing study. The present data indicated a significantly higher rate of progression in patients treated with corticosteroids and the possible positive effect of NSAID use at the initiation of nivolumab treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde/métodos , Corticosteroides/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Estimativa de Kaplan-Meier , Masculino , Metformina/administração & dosagem , Pessoa de Meia-Idade , Nivolumabe/administração & dosagem , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Probióticos/administração & dosagem , Modelos de Riscos Proporcionais , Inibidores da Bomba de Prótons/administração & dosagem , Estudos Retrospectivos
12.
Mod Pathol ; 33(6): 1146-1156, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907375

RESUMO

Lung adenocarcinoma (LAC) is the most common form of lung cancer that increases in non-smokers at younger age. Altered protein glycosylation is one of the hallmarks of malignancy, its role in cancer progression is still poorly understood. In this study, we report mass spectrometric (MS) analysis of N-glycans released from fresh or defrosted tissue specimens from 24 patients with LAC. Comparison of cancerous versus adjacent healthy tissues revealed substantial differences in N-glycan profiles associated with disease. The significant increase in paucimannose and high-mannose glycans with 6-9 mannose residues and decline in the sialylated complex biantenary core fucosylated glycan with composition NeuAcGal2GlcNAc2Man3GlcNAc2Fuc were general features of tumors. In addition, 42 new N-glycan compositions were detected in cancerous tissues. The prominent changes in advanced disease stages were mostly observed in core fucosylated N-glycans with additional fucose (Fuc) residue/s and enhanced branching with non-galactosylated N-acetyl-glucosamine (GlcNAc) units. Both of these monosaccharide types were linked preferably on the 6-antenna. Importantly, as compared with noncancerous tissues, a number of these significant changes were clearly detectable early on in stage I. Application of N-glycan data obtained from tissues was next assessed and validated for evaluation of small sized biopsies obtained via bronchoscopy. In summary, observed alterations and data of newly detected N-glycans expand knowledge about the glycosylation in LAC and may contribute to research in more tailored therapies. Moreover, the results demonstrate effectiveness of the presented approach for utility in rapid discrimination of cancerous from healthy lung tissues.


Assuntos
Adenocarcinoma de Pulmão/metabolismo , Neoplasias Pulmonares/metabolismo , Polissacarídeos/metabolismo , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Progressão da Doença , Feminino , Glicosilação , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade
13.
In Vivo ; 34(1): 369-379, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31882501

RESUMO

AIM: To compare survival outcomes in patients with non-small cell lung cancer (NSCLC) treated with modern-era drugs (antifolates, antiangiogenics, tyrosine kinase and anaplastic lymphoma kinase inhibitors, immunotherapy) with treatment initiation in 2011-12 and 2015-16, respectively. PATIENTS AND METHODS: Prospective data from Czech TULUNG Registry (960 patients from 2011-12 and 512 patients from 2015-16) were analyzed. Kaplan-Meier analysis was used to estimate overall survival (OS) and progression-free survival (PFS); Cox proportional hazards model to assess factors associated with 2-year survival. RESULTS: Survival at 2 years was more frequent in cohort 2015-16 compared to cohort 2011-12 (43.2% vs. 24% for adenocarcinoma; p<0.001 and 28.7% vs. 11.8% for squamous-cell lung carcinoma; p=0.002). Assignment to cohort 2015-16 and treatment multilinearity (two or more lines in sequence) were associated with higher probability of 2-year survival (hazard ratio=0.666 and hazard ratio=0.597; p<0.001). Comparison of 2-year survivors from both cohorts showed no differences. CONCLUSION: Survival at 2 years probability in stage IIIB-IV NSCLC doubled between 2011-12 and 2015-16; advanced-stage NSCLC may be considered a chronic disease in a large proportion of patients.


Assuntos
Adenocarcinoma de Pulmão/mortalidade , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/mortalidade , Neoplasias Pulmonares/mortalidade , Sistema de Registros/estatística & dados numéricos , Adenocarcinoma de Pulmão/epidemiologia , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Doença Crônica , Estudos de Coortes , Terapia Combinada , República Tcheca/epidemiologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
14.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1134-1135: 121857, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31790918

RESUMO

In this study, the ionic profile and pH of exhaled breath condensate (EBC) in a group of patients with acid and weakly acid reflux and no-reflux controls were compared. A portable sampler was used for non-invasive EBC collection from five exhalations. The ionic profile (anions, cations, organic acids) and pH of the collected EBC samples were measured by capillary electrophoresis with contactless conductivity detection and a pH microelectrode, respectively. Several ions were elevated in the patient groups. Sodium cation was elevated in weakly acid reflux (significance level p < 0.01) and acid reflux (p < 0.05) compared to no-reflux controls. Butyrate and propionate were elevated in both acid reflux and weakly acid reflux compared to no-reflux controls (butyrate: p < 0.01, propionate: p < 0.05). The median values of pH (after de-aeration with N2) were also significantly higher (p < 0.01) in groups with acid reflux and weakly acid reflux than in the control group with no reflux. The ionic analysis and simultaneous pH measurement offer a simple, cheap, fast, and non-invasive approach in gastroesophageal reflux disease diagnostics.


Assuntos
Testes Respiratórios/métodos , Eletroforese Capilar/métodos , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/metabolismo , Íons/análise , Adulto , Idoso , Butiratos/análise , Feminino , Humanos , Concentração de Íons de Hidrogênio , Íons/metabolismo , Masculino , Pessoa de Meia-Idade , Propionatos/análise , Sódio/análise
15.
Anal Chem ; 91(13): 7985-7990, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31141660

RESUMO

Fucosylation is a common modification, and its site in glycans refers to different normal and pathological processes. Despite intensive research, there is still a lack of methods to discriminate unambiguously the fucose position in one-step. In this work, we propose utility of phenylhydrazine (PHN) labeling for structural studies of fucosylated N-glycans by tandem MALDI mass spectrometry (MS) in the positive ion mode. PHN-tag influences the production of specific ion types, and the MS/MS fragmentation pattern provides useful structural information. All types of core fucosylated N-glycans have produced two abundant ions consistent with B- and C-glycosidic cleavages corresponding to the loss of the FucGlcNAcPHN residue with a mass 457 and 441 Da from the parent ions. These types of fragment ions in N-glycans without a core fucose were associated with the loss of the GlcNAcPHN unit (311 and 295 Da), and fucose cleavage followed the loss of the chitobiose residue. Since diagnostic useful cleavages produce peaks with significant intensities, this approach is also beneficial for rapid recognition of antenna from core fucosylation in glycans detected with low abundances. Moreover, in multifucosylated glycans, this type of labeling allows to distinguish how many fucose residues are on the specific antenna and provides additional information on the topology of N-glycans, such as type of antennarity or identification of bisecting moiety. The practical applicability of the approach is demonstrated on the analysis of multifucosylated N-glycans detected with lower abundances in lung cancer samples.


Assuntos
Fucose/análise , Polissacarídeos/química , Glicosilação , Humanos , Neoplasias Pulmonares/química , Fenil-Hidrazinas/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
16.
J Clin Gastroenterol ; 53(5): 355-360, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29863588

RESUMO

GOAL: To evaluate the analytical parameters of a lateral flow (LF) pepsin immunoassay (Peptest) and assess its suitability in the diagnostics of gastroesophageal reflux disease (GERD). BACKGROUND: Peptest is a noninvasive assay to analyze pepsin in saliva, intended for use in GERD diagnostics. Although commercialized, fundamental studies on its performance are missing. The assay therefore requires basic analytical parameter evaluation to assess its suitability in clinical practice. STUDY: Assay reaction's time dependence, reader device repeatability, and individual LF devices and longitudinal pepsin concentration reproducibility in individual subjects was evaluated. Salivary pepsin was analyzed in 32 GERD patients with extraesophageal reflux symptoms and 13 healthy individuals. RESULTS: The assay's signal increase is not completed at the recommend readout time and continues to increase for another 25 minutes. The relative standard deviation of measurement was good when using the same LF device, ranging from 2.3% to 12.9%, but the reproducibility of 10 different individual LF devices was poor. The random error when analyzing the same saliva sample on 10 LF devices was as high as 36 ng/mL and this value is thus suggested as the positivity cut-off. Pepsin concentration in individual subjects during a 10-day period varied significantly. The sensitivity of the Peptest was 36.8% in the group with acid reflux and 23.1% in the group with weakly acid reflux. The specificity was 61.5%. CONCLUSIONS: The Peptest assay's sensitivity and specificity is low, the results are highly variable and it should not be used as a near-patient diagnostic method in primary care.


Assuntos
Refluxo Gastroesofágico/diagnóstico , Imunoensaio , Pepsina A/metabolismo , Saliva/metabolismo , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
17.
Anticancer Res ; 38(12): 6771-6782, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30504389

RESUMO

AIM: To investigate potential associations between clinical and standard peripheral blood biomarkers and clinical outcome in patients with non-small cell lung cancer (NSCLC) treated with nivolumab. PATIENTS AND METHODS: A total of 120 patients with advanced NSCLC treated at seven comprehensive cancer care centers were analyzed in this national retrospective study. Survival statistics were evaluated using the Kaplan-Meier method and Cox analysis. RESULTS: Among clinical parameters, histology was significantly associated with progression-free survival. Univariate Cox-proportional hazards model indicated prognostic and predictive role of a panel of laboratory parameters reflecting chronic inflammatory pattern (elevated neutrophil count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, C-reactive protein and decrease in hemoglobin and albumin). Higher serum calcium concentration was also associated with nivolumab treatment effect. CONCLUSION: Tumor histology was the only clinical parameter predicting the outcome of nivolumab treatment. Among the laboratory parameters, our analysis identified a laboratory panel reflecting chronic inflammation as a potential predictive marker of nivolumab treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inflamação/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/uso terapêutico , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Doença Crônica , Feminino , Humanos , Inflamação/complicações , Inflamação/mortalidade , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida
18.
BMC Cancer ; 18(1): 1144, 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30458807

RESUMO

BACKGROUND: A minority of European countries have participated in international comparisons with high level data on lung cancer. However, the nature and extent of data collection across the continent is simply unknown, and without accurate data collection it is not possible to compare practice and set benchmarks to which lung cancer services can aspire. METHODS: Using an established network of lung cancer specialists in 37 European countries, a survey was distributed in December 2014. The results relate to current practice in each country at the time, early 2015. The results were compiled and then verified with co-authors over the following months. RESULTS: Thirty-five completed surveys were received which describe a range of current practice for lung cancer data collection. Thirty countries have data collection at the national level, but this is not so in Albania, Bosnia-Herzegovina, Italy, Spain and Switzerland. Data collection varied from paper records with no survival analysis, to well-established electronic databases with links to census data and survival analyses. CONCLUSION: Using a network of committed clinicians, we have gathered validated comparative data reporting an observed difference in data collection mechanisms across Europe. We have identified the need to develop a well-designed dataset, whilst acknowledging what is feasible within each country, and aspiring to collect high quality data for clinical research.


Assuntos
Coleta de Dados/estatística & dados numéricos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Oncologia/estatística & dados numéricos , Coleta de Dados/métodos , Bases de Dados Factuais/estatística & dados numéricos , Europa (Continente) , Humanos , Oncologia/métodos
19.
Cas Lek Cesk ; 157(5): 226-236, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30441934

RESUMO

Lung cancer is one of the most common cancers worldwide. Approximately 85 % of lung cancers are non-small cell lung cancers while 15 % are small cell lung cancers. Histologically, following subtypes of non-small cell cancer are distinguished: adenocarcinoma (38.5 % of all lung cancers), squamous cell carcinoma (20 %) and large cell carcinoma (3 %). Over recent years, the incidence of adenocarcinoma has been increasing. Squamous cell carcinoma is more commonly associated with smoking while adenocarcinoma is the most common histological type in non-smokers. The treatment of non-small cell lung cancer is decided according to clinical stage, morphological diagnosis, and the performance status of the patient. Early-stage patients are typically indicated for surgery. In some cases, adjuvant therapy is indicated. In locally advanced and metastatic stages, chemotherapy, biological treatment, and, recently, immunotherapy is indicated. Radiotherapy should also be considered for locally advanced disease. In small-cell lung cancer, the combination of etoposide and cisplatin or etoposide and carboplatin is still considered standard chemotherapy. Radiotherapy is an integral part of treatment of either type of lung cancer. Keywords: lung cancer, non-small cell lung cancer, small cell lung cancer, chemotherapy, biological therapy, radiotherapy, immunotherapy.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Terapia Combinada , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Estadiamento de Neoplasias
20.
Vnitr Lek ; 63(11): 786-795, 2018.
Artigo em Tcheco | MEDLINE | ID: mdl-29303280

RESUMO

In the broadest sense, the term immunocompromised individual means a person with any impairment of infection resistance, whether it is deficiency or impairment of innate resistance (by another name impairment of non-specific resistance), or impairment of acquired resistance (impairment of specific immunity). Pneumonia in immunocompromised patients is characterized by a different microbiological spectrum. Apart from common pathogens there are also opportunistic agents involved in this group of patients. Management of pneumonia in immunocompromised patients is often decisive for their future fate. Very rare are innate immune deficiencies. Acquired immune deficiencies are far more common. They are often combined with disorders of non-specific resistance. The most frequent cause of acquired immune deficiency is another illness or a medical treatment. The diagnosing and treatment of pneumonias in immunocompromised patients are usually highly specialized and they unquestionably require a collaboration with microbiologists who are concerned with these problems.Key words: diagnostics - etiology - pneumonia in immunocompromised patients - prophylaxis - treatment.


Assuntos
Hospedeiro Imunocomprometido , Pneumonia/imunologia , Humanos , Pneumonia/diagnóstico , Pneumonia/tratamento farmacológico
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