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Gliomas are the most common central nervous system tumors. New technologies, including genetic research and advanced statistical methods, revolutionize the therapeutic approach to the patient and reveal new points of treatment options. Moreover, the 2021 World Health Organization Classification of Tumors of the Central Nervous System has fundamentally changed the classification of gliomas and incorporated many molecular biomarkers. Given the rapid progress in neuro-oncology, here we compile the latest research on prognostic and predictive biomarkers in gliomas. In adult patients, IDH mutations are positive prognostic markers and have the greatest prognostic significance. However, CDKN2A deletion, in IDH-mutant astrocytomas, is a marker of the highest malignancy grade. Moreover, the presence of TERT promoter mutations, EGFR alterations, or a combination of chromosome 7 gain and 10 loss upgrade IDH-wildtype astrocytoma to glioblastoma. In pediatric patients, H3F3A alterations are the most important markers which predict the worse outcome. MGMT promoter methylation has the greatest clinical significance in predicting responses to temozolomide (TMZ). Conversely, mismatch repair defects cause hypermutation phenotype predicting poor response to TMZ. Finally, we discussed liquid biopsies, which are promising diagnostic, prognostic, and predictive techniques, but further work is needed to implement these novel technologies in clinical practice.
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Biomarcadores Tumorais , Neoplasias do Sistema Nervoso Central , Glioma , Proteínas de Neoplasias , Temozolomida/uso terapêutico , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/metabolismo , Metilação de DNA/efeitos dos fármacos , DNA de Neoplasias/genética , DNA de Neoplasias/metabolismo , Glioma/diagnóstico , Glioma/tratamento farmacológico , Glioma/genética , Glioma/metabolismo , Humanos , Mutação , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , PrognósticoRESUMO
Fluorescence in situ hybridization (FISH) is a standard technique used in routine diagnostics of genetic aberrations. Thanks to simple FISH procedure is possible to recognize tumor-specific abnormality. Its applications are limited to designed probe type. Gene rearrangements e.g., ALK, ROS1 reflecting numerous translocational partners, deletions of critical regions e.g., 1p and 19q, gene fusions e.g., COL1A1-PDGFB, genomic imbalances e.g., 6p, 6q, 11q and amplifications e.g., HER2 are targets in personalized oncology. Confirmation of genetic marker is frequently a direct indication to start specific, targeted treatment. In other cases, detected aberration helps pathologists to better distinguish soft tissue sarcomas, or to state a final diagnosis. Our main goal is to show that applying FISH to formalin-fixed paraffin-embedded tissue sample (FFPE) enables assessing genomic status in the population of cells deriving from a primary tumor or metastasis. Although many more sophisticated techniques are available, like Real-Time PCR or new generation sequencing, FISH remains a commonly used method in many genetic laboratories.
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Hibridização in Situ Fluorescente , Neoplasias/diagnóstico , Biomarcadores Tumorais/genética , Coloração Cromossômica , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente/métodos , Sondas Moleculares , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/terapia , Medicina de Precisão , Reprodutibilidade dos TestesRESUMO
The long-range control of gene expression is facilitated by chromatin looping and can be detected using chromosome conformation capture-3C. Here we focus on the chromatin architecture of the PTBP3 (Polypyrimidine tract binding protein 3) locus to evaluate its potential role in regulating expression of the gene. PTBP3 expression in prostate cancer cell lines is found significantly higher compared to skin fibroblasts using real-time PCR (p < 0.05) and digital droplet PCR (p < 0.01). Exploration of the chromatin spatial architecture of a nearly 200-kb fragment of chromosome 9 encompassing the PTBP3 gene identified two elements located 63 kb upstream and 48 kb downstream of PTBP3, which looped specifically to the PTBP3 promoter. These elements contain histone acetylation patterns characteristic of open chromatin regions with active enhancers. Our results reveal for the first time that long-range chromatin interactions between the -63 kb and +48 kb loci and the PTBP3 promoter regulate the expression of this gene in prostate cancer cells. These interactions support an open chromatin form for the PTBP3 locus in cancer cells and the three-dimensional structural model proposed in this paper.
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Cromossomos/química , Cromossomos/genética , Conformação de Ácido Nucleico , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genética , Elementos de Resposta , Sítio de Iniciação de Transcrição , Linhagem Celular , Cromatina/química , Cromatina/genética , Expressão Gênica , Loci Gênicos , Histonas/metabolismo , Humanos , Masculino , Modelos Moleculares , Regiões Promotoras Genéticas , Neoplasias da Próstata/genética , RNA Mensageiro/genéticaRESUMO
AIM OF THE STUDY: The main purpose of this study was to assess detection of mutations in the epidermal growth factor receptor (EGFR) gene in circulating tumor DNA (ctDNA) as a tool for EGFR tyrosine kinase inhibitor (TKI) monitoring therapy. MATERIAL AND METHODS: The study was conducted using 20 samples from 7 adenocarcinoma patients treated with TKIs. Blood samples for ctDNA analysis were collected in 2015-2016. ctDNA was isolated using the QIAamp Circulating Nucleic Acid Kit (Qiagen) and analyzed using the ctEGFR Mutation Detection Kit (EntroGen). RESULTS: The most common exon 19 deletion and p.Leu858Arg mutation in exon 21 of the EGFR gene were detected. We observed a correlation between stabilization of patient condition and the lack of p.Thr790Met mutation detection in ctEGFR during TKI treatment (2 out of 7 patients). We also observed a correlation between progression of the disease and p.Thr790Met mutation detection in ctEGFR (3 out of 7 cases). We did not detect ctDNA p.Thr790Metp in two patients in whom progression occurred shortly thereafter. Last but not least, we noticed that good organization during plasma collection and transportation (average time of 6 minutes and 30 seconds) allows to use K2EDTA tubes. CONCLUSIONS: When tissue is limited or insufficient, analysis of the ctEGFR mutational status can be considered as an alternative tool for qualifying patients with non-small cell lung cancer (NSCLC) for TKI therapy, also as a potential monitoring tool. The plasma p.Thr790Met-negative result needs to be verified for the presence of p.Thr790Met-positive tumor tissue.
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AIM OF THE STUDY: To determine the cost-effectiveness of lung cancer (LC) screening with low-dose computerised tomography of the chest, as compared to an approach without screening, reimbursed today by the National Health Fund (NHF) in Poland. MATERIAL AND METHODS: In order to analyse the current costs of diagnostic and therapeutic procedures of a model LC patient treated today, a model group consisting of 199 consecutive patients diagnosed and treated in the Oncology Centre in Bydgoszcz, Poland from January 2007 to April 2010 was used. The number and type of performed procedures in this group was obtained from the Polish Register of Neoplasms and the NHF. Only direct medical costs were analysed. To calculate the total costs of screening, diagnostics, and treatment of the hypothetical LC patient who would have cancer diagnosed with screening CT, data from the literature and costs calculated for the model group were used. Prices of procedures were obtained from the price list of the NHF on 30 April 2010 and did not change from that time until June 2014. One-way sensitivity analysis was performed. RESULTS: The average cost per LC patient, diagnosed and treated without screening, is 5567.50 EUR, and median LC-specific survival is one year. In the hypothetical LC patient with cancer diagnosed by screening, the average cost is 13689.35 EUR per LC patient, with a median LC-specific survival of at least seven years. A calculated incremental cost-effectiveness ratio (ICER) is 1353.64 EUR/year of life gained. CONCLUSIONS: Lung cancer screening with low-dose CT would be highly cost-effective in Poland.
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BACKGROUND: Patients with pathological tissue mass in thoracic cage found with imaging require histopathological or cytological confirmation of malignancy before treatment. The tissue material essential for patomorphological evaluation can be acquired with fine-needle aspiration biopsies (FNAB) controlled with CT and core-needle biopsy (CNB) under real-time CT fluoroscopy guidance. The purpose of this work is to carry out a retrospective analysis of the two methods with regards to their informativity, frequency and the kind of complications. MATERIAL/METHODS: From January, 2012 to May 2013, 76 core-needle biopsies of lung and mediastinum tumors were conducted and compared with 86 fine-needle aspiration biopsies(FNAB) of lung and mediastinum tumors, including 30 patients who underwent FNAB and were referred to CNB in order to specify the diagnosis. RESULTS: Complete histopathological diagnosis was made in 91% with the use of CNB and in 37% when FNAB was the chosen method. Early complications were observed in 32% patients who underwent BG and in group of 11% who underwent FNAB. Late complications, however, appeared in 29% patients after CNB and 13% after FNAB. In 24 cases CNB specified the complete diagnosis. CONCLUSIONS: Core-needle biopsy in comparison to fine-needle aspiration biopsy has more frequent rate of negligible complications, however, it offers higher diagnostic yield for diagnostic of lung and mediastinum neoplastic disease and allows for more precise diagnosis of focal lesions.
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AIM: The study aimed to determine a prognostic value of primary tumor volume measured on the basis of integrated positron emission tomography-computerized tomography (PET-CT) in terms of mediastinal nodal metastases (N2) prediction in non-small-cell lung cancer (NSCLC) patients with PET-CT N2 negative lymph nodes. METHODS: The records of 70 potentially operable NSCLC patients treated with surgical resection were analyzed. All patients underwent diagnostic, preoperative PET-CT, which was the basis for tumor volume calculations as well as the evaluation of N2 nodes status. The logistic regression analysis was employed to determine correlation between mediastinal nodal involvement and volume of primary tumor (izoSUV2.5 volume), that is the volume of primary tumor inside SUV 2.5 line, tumor histology, location (peripheral vs. central), hilar node status. RESULTS: A statistically significant correlation between mediastinal node involvement and izoSUV2.5 volume, tumor histology, locations peripheral vs. central and hilar node status was found. The risk of mediastinal lymph node metastasis is 24% for tumor volume of 100 cm(3) and increases up to 40% for tumor volume of 360 cm(3). An increase of tumor volume by 1 cm(3) increases the risk of lymph node disease by 0.3%. Tumor histology adenocarcinoma vs. squamous cell carcinoma increases the risk of mediastinal lymph node involvement by 195%, location central vs. peripheral by 68% and hilar node involvement by 166%. CONCLUSIONS: The study demonstrates that izoSUV2.5 volume of primary tumor may be considered as a prognostic factor in NSCLC patients, since it strongly correlates with mediastinal lymph node pathological status. This correlation is modified by primary tumor location, histology and hilar node involvement.
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BACKGROUND: Studies have demonstrated a lower incidence of complications after video-assisted thoracoscopic surgery (VATS) lobectomy compared with thoracotomy, but the data on in-hospital and 90-day mortality are inconclusive. This study analyzed whether surgical approach, VATS or thoracotomy, was related to early mortality of lobectomy in lung cancer and determined the differences between in-hospital and 90-day mortality. METHODS: Data of all patients with non-small cell lung cancer who underwent lobectomy between January 1, 2007, and July 30, 2018, were retrieved from Polish National Lung Cancer Registry. Included were 31 433 patients who met all study criteria. After propensity score matching, 4946 patients in the VATS group were compared with 4946 patients in the thoracotomy group. RESULTS: Compared with thoracotomy, VATS lobectomy was related to lower in-hospital (1.5% vs 0.9%, P = .004) and 90-day mortality (3.4% vs 1.8%, P < .001). Mortality at 90 days was twice as high as in-hospital mortality in both the VATS (1.8% vs 0.9%, P < .001) and thoracotomy groups (3.4% vs 1.5%, P < .001). Postoperative complications were less common after VATS compared with thoracotomy (23.6% vs 31.8%, P < .001). CONCLUSIONS: VATS lobectomy is associated with lower in-hospital and 90-day mortality compared with thoracotomy and should be recommended for lung cancer treatment, if feasible. Patients should also be closely monitored after discharge from the hospital, because 90-day mortality is significant higher than in-hospital mortality.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Pneumonectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Cirurgia Torácica Vídeoassistida/efeitos adversos , Toracotomia/efeitos adversos , Estudos de Coortes , Estudos RetrospectivosRESUMO
OBJECTIVES: To evaluate the incidence of HPV infection, and the frequency of the various genotypes, using mRNA and DNA testing; to assess their relationship with the cervical lesions and women's age in the Polish patients. STUDY DESIGN: A group of 1840 women, most of whom had abnormal cytology, from the Franciszek Lukaszczyk Oncology Centre in Bydgoszcz, Poland were screened for presence of at least one of 13 high risk HPV. Following that, 545 HPV DNA positive women were tested for HPV infection using HPV mRNA with the Nucleic Acid Sequence-Based Amplification Assay (NASBA) method. RESULTS: In our study group, 70.1% had DNA HPV positive results. Only 4% of the women had normal cytology. Among 545 HPV DNA positive patients, 36.3% had HPV mRNA positive tests. Moreover, 48% of the HPV mRNA positive patients were infected with HPV 16, followed by 18 (12.6%), 31 (10.1%), 33 (8.6%%), 45 (4.5%), and 16.2% of HPV mRNA positive women were infected with more than one HPV genotype. Furthermore, we found that in women under 30, HPV DNA positivity was higher than HPV mRNA positivity, supporting the hypothesis that younger women's infections are mostly temporary. CONCLUSIONS: The differences in HPV prevalence and genotype distribution observed in our study may have an impact on the efficacy of HPV vaccinations for cervical cancer and the development of screening programs, which should be examined further in future studies.
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Infecções por Papillomavirus , Neoplasias do Colo do Útero , DNA Viral , Detecção Precoce de Câncer , Feminino , Genótipo , Humanos , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Polônia/epidemiologia , RNA , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologiaRESUMO
INTRODUCTION: The accurate detection of genetic variants such as single substitutions (IDH1/2, TERT), chromosomal abnormalities (CDKN2A, 1p/19q deletions, and EGFR amplifications), or promoter methylations (MGMT) is critical for glioma patient management, as emphasized in the World Health Organization's (WHO's) most recent classification in 2021 (WHO CNS5). The purpose of this study was to evaluate novel innovative methods for determining IDH1/2 status in the context of WHO CNS5. METHODS: Multiple biomarkers were simultaneously screened using next-generation sequencing (NGS) on 34 glioma samples. In cases where the IDH1/2 status determined by immunohistochemistry (IHC) or multiplex ligation-dependent probe amplification (MLPA) was inconsistent with the NGS results, quantitative polymerase chain reaction (qPCR) and Sanger sequencing were performed to resolve the adjudicated discrepancy. RESULTS: IDH1/2 NGS results differ from IHC (7/13 samples) as well as MLPA reports (1/4 samples). All NGS findings were confirmed by qPCR and Sanger sequencing. WHO CNS5 requires assessment of multiple mutations for glioma classification. CONCLUSIONS: We demonstrated that qPCR or NGS performed in reference genetic laboratories, rather than IHC, is the most reliable method for IDH1/2 analysis. Clinicians should be aware of discrepancies in MLPA or IHC results and seek reconsultation in facilities with extensive access to advanced molecular technologies. Moreover, we proposed a new algorithm for the molecular diagnostic procedures in glioma patients based on the WHO CNS5.
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Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/diagnóstico , Imuno-Histoquímica , Glioma/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mutação , Organização Mundial da Saúde , Isocitrato Desidrogenase/genéticaRESUMO
Decreased repair of oxidative DNA damage is a risk factor for developing certain human malignancies. We have previously found that the capacity of 8-oxo-7,8-dihydroguanine repair was lower in leukocytes of NSCLC patients than in controls. To explain these observations, we searched for mutations and polymorphisms in the OGG1 gene among 88 NSCLC patients and 79 controls. One patient exhibited a heterozygous mutation in exon 1, which resulted in Arg46Gln substitution. Normal lung and tumor tissue carrying this mutation showed markedly lower 8-oxoG incision activity than the mean for all patients. The predominant polymorphism of OGG1 was Ser326Cys. A significant difference was observed in the frequencies of the OGG1 variants between populations of NSCLC patients and controls. The frequency of the Cys326 allele and the number of Cys326Cys homozygotes was higher among patients than controls. In individuals with either Ser326Cys or Cys326Cys genotype 8-oxoG incision rate was lower than in those with both Ser326 alleles, either in lung or leukocytes. Moreover, 8-oxodG level was higher in lung tissue and leukocytes of patients carrying two Cys326 alleles and in leukocytes of patients with the Ser326Cys genotype. We also screened for polymorphisms of the XRCC1 gene. Only heterozygotes of the XRCC1 variants Arg194Trp, Arg280His and Arg399Gln were found among patients and controls, with the frequency of Arg280His being significantly higher among patients. NSCLC patients with Arg280His or Arg399Gln polymorphism revealed lower 8-oxoG incision activity in their lung tissues, but not in leukocytes. We can conclude that the OGG1 Ser326Cys polymorphisms may have an impact on the efficiency of 8-oxoG incision in humans and the XRCC1 His280 and Gln399 may influence the OGG1 activity in tissues exposed to chronic oxidative/inflammatory stress. Higher frequency of the OGG1 Cys326 allele among NSCLC patients may partially explain the impairment of the 8-oxoG repair observed in their leukocytes.
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Carcinoma Pulmonar de Células não Pequenas/genética , Reparo do DNA/genética , Proteínas de Ligação a DNA/genética , Desoxiguanosina/análogos & derivados , Guanina/análogos & derivados , Neoplasias Pulmonares/genética , Polimorfismo Genético , 8-Hidroxi-2'-Desoxiguanosina , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Desoxiguanosina/genética , Feminino , Guanina/metabolismo , Humanos , Leucócitos/metabolismo , Pulmão , Masculino , Pessoa de Meia-Idade , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
(1) Background: Although, in the mutated BRCA detected in the Polish population of patients with breast cancer, there is a large percentage of recurrent pathogenic variants, an increasing need for the assessment of rare BRCA1/2 variants using NGS can be observed. (2) Methods: We studied 75 selected patients with breast cancer (negative for the presence of 5 mutations tested in the Polish population in the prophylactic National Cancer Control Program). DNA extracted from the cancer tissue of these patients was used to prepare a library and to sequence all coding regions of the BRCA1/2 genes. (3) Results: We detected nine pathogenic variants in 8 out of 75 selected patients (10.7%). We identified one somatic and eight germline variants. We also used different bioinformatic NGS software programs to analyze NGS FASTQ files and established that tertiary analysis performed with different tools was more likely to give the same outcome if we analyzed files received from secondary analysis using the same method. (4) Conclusions: Our study emphasizes (i) the importance of an NGS validation process with a bioinformatic procedure included; (ii) the importance of screening both somatic and germline pathogenic variants; (iii) the urgent need to identify additional susceptible genes in order to explain the high percentage of non-BRCA-related hereditary cases of breast cancer.
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Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Biologia Computacional/métodos , Mutação , Adulto , Idoso , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Pessoa de Meia-Idade , Polônia , Análise de Sequência de DNARESUMO
INTRODUCTION: Infections are a part of the natural course of lung cancer but few studies have looked at the clinical and microbiological documentation of infections in these patients. The aim of this study is to analyze the profile of potentially pathogenic bacteria that colonize the bronchial tree in patients with primary lung cancer. MATERIAL AND METHODS: The study was conducted from January 2006 to August 2007. It included 44 consecutive patients (34 males and 10 females) with primary lung cancer aged from 38 to 77 (mean age of 57.9 years). In all patients, bronchoalveolar lavage (BAL) was performed during bronchofiberoscopy. Obtained BAL fluid was subjected to microbiological examination. The number of bacteria present in 1 ml of fluid was estimated by quantitative culture. A diagnostic level was set on >or= 104 cfu/ml. RESULTS: In 26 (59.1%) of 44 patients physiologic bacterial flora was found in the bronchial tree. In three cases (6.8%), potentially pathological bacteria were cultured but their number was < 104 cfu/ml. In 15 (34.1%) cases, the colonization of potentially pathogenic bacteria was >or= 104 cfu/ml. Both Gram-positive and Gram-negative bacteria were isolated. The most frequently isolated bacterium in the first group was Streptococcus pneumoniae (n = 7), and in the second group Haemophilus influenzae (n = 3). Multibacterial colonization was found in five patients (11.4%). In four cases (9.1%), the bronchial tree was colonized simultaneously by two and in one case [2.3%] by three types of micro-organism. Multi-drug-resistant strains were not found in the examined materials but among Streptococcus pneumoniae the constitutive MLSB phenotype was observed. CONCLUSIONS: 1. Approximately 30% of patients with lung cancer had a respiratory tract colonized by micro-organisms whose number was higher than the assumed diagnostic level. 2. Among micro-organisms colonizing the lower respiratory tract, Gram-positive cocci such as Streptococcus pneumoniae and Staphylococcus aureus were dominant. 3. The analysis of antibiotic-resistance did not detect multi-drug-resistant micro-organisms but some strains of Streptococcus pneumoniae exhibited resistance to macrolide, lincosamide and streptogramin B.
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Líquido da Lavagem Broncoalveolar/microbiologia , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Neoplasias Pulmonares/complicações , Infecções Respiratórias/microbiologia , Adulto , Idoso , Broncoscopia/métodos , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Polônia , Sistema Respiratório/microbiologia , Estudos RetrospectivosRESUMO
Largescale projects, such as The Cancer Genome Atlas (TCGA), Human Epigenome Project (HEP) and Human Epigenome Atlas (HEA), provide an insight into DNA methylation and histone modification markers. Changes in the epigenome significantly contribute to the initiation and progression of cancer. The goal of the present study was to characterize the prostate cancer malignant transformation model using the CpG island methylation pattern. The Human Prostate Cancer EpiTect Methyl II Signature PCR Array was used to evaluate the methylation status of 22 genes in prostate cancer cell lines: PC3, PC3M, PC3MPro4 and PC3MLN4, each representing different metastatic potential in vivo. Subsequently, it was ascertained whether DNA methylation plays a role in the expression of these genes in prostate cancer cells. Hypermethylation of APC, DKK3, GPX3, GSTP1, MGMT, PTGS2, RASSF1, TIMP2 and TNFRSF10D resulted in downregulation of their expression in prostate cancer cell lines as compared to WT fibroblasts. Mining of the TCGA data deposited in the MetHC database found increases in the methylation status of these 9 genes in prostate cancer patients, further supporting the role of methylation in altering the expression of these genes in prostate cancer. Future studies are warranted to investigate the role of these proteins in prostate cancer development.
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Metilação de DNA , Epigenômica/métodos , Perfilação da Expressão Gênica/métodos , Neoplasias da Próstata/genética , Estudos de Casos e Controles , Linhagem Celular Tumoral , Ilhas de CpG , Bases de Dados Genéticas , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Masculino , Regiões Promotoras GenéticasRESUMO
Epigenetic patterns, such as DNA methylation, histone modifications, and non-coding RNAs, can be both driver factors and characteristic features of certain malignancies. Aberrant DNA methylation can lead to silencing of crucial tumor suppressor genes or upregulation of oncogene expression. Histone modifications and chromatin spatial organization, which affect transcription, regulation of gene expression, DNA repair, and replication, have been associated with multiple tumors. Certain microRNAs (miRNAs), mainly those that silence tumor suppressor genes and occur in a greater number of copies, have also been shown to promote oncogenesis. Multiple patterns of these epigenetic factors occur specifically in certain malignancies, which allows their potential use as biomarkers. This review presents examples of tests for each group of epigenetic factors that are currently available or in development for use in early cancer detection, prediction, prognosis, and response to treatment. The availability of blood-based biomarkers is noted, as they allow sampling invasiveness to be reduced and the sampling procedure to be simplified. The article stresses the role of epigenetics as a crucial element of future cancer diagnostics and therapy.
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Biomarcadores Tumorais/genética , Epigênese Genética , Neoplasias/genética , Prognóstico , Carcinogênese/genética , Metilação de DNA/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Oncologia/tendências , MicroRNAs/genética , Neoplasias/patologiaRESUMO
AIMS: To compare transcatheter aortic valve replacement TAVR with self-expandable first-generation Medtronic CoreValve with new-generation Evolut R devices in patients with aortic stenosis. METHODS: Multiple databases were screened for all available reports directly or indirectly comparing CoreValve vs Evolut R. Primary endpoint was device success. Procedural, functional and clinical outcomes were assessed as well. RESULTS: Ten retrospective series including 12 294 pts. were found. Overall device success rate was 95.5% and was statistically higher in the Evolut R treated patients as compared with CoreValve: 96.6 vs. 94.8%, respectively; RR (risk ratio) 95%CIs (confidence intervals): 1.02 (1.00-1.04); P = 0.01. There were no statistical differences with regard to postoperative mean aortic gradients 8.5 +/- 5.3 vs 7.9 +/- 4.6 with Evolut R and CoreValve. Evolut R valve demonstrated nearly 50% reduction of the risk for moderate-to-severe paravalvilar leak 0.55 (0.39-0.79); P = 0.001; 60% statistically significant lower risk of developing myocardial injury 0.40 (0.22-0.72); P = 0.002 and numerical reductions in the risk of acute kidney injury, vascular complications and bleeding. Together with significantly reduced risk of permanent pacemaker implantation (0.80 [0.67-0.96]; P = 0.02) the above benefits were associated with 40% reduction in the risk of 30-day all-cause mortality with Evolut R as compared to CoreValve: 0.60 (0.37-1.00); P = 0.05. CONCLUSIONS: The use of new-generation Evolut R was associated with improved procedural, functional and clinical outcomes compared with the CoreValve device.
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Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter/instrumentação , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/fisiopatologia , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/etiologia , Desenho de Prótese , Recuperação de Função Fisiológica , Fatores de Risco , Fatores de Tempo , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/mortalidade , Resultado do TratamentoRESUMO
In the majority of the cases it is difficult to evaluate the type of the subcentimeter pulmonary nodule basing on the clinical picture (age of the patient, cigarette smoking history, history of antecedent cancer) and radiographic diagnostics (CT HRCT PET). Usually it is possible only to estimate the probability of malignancy of lesions less than 1 cm. Transthoracic needle aspiration and bronchoscopy have been shown to provide no measurable preoperative benefit to the patient. The high-likelihood nodules should be excised if feasible and the low-likelihood lesions should be followed with serial CTs. Any substantial changes in shape, density and volumetric growth are indication for resection of the nodule. In those patients in whom these lesions are followed and found to represent cancer on subsequent CTs and work-up, there does not seem to be a worsened survival. In the selected cases of subcentimeter lung cancer based on tumor location, its radiographic and histological characteristics the intentional sublobar, parenchyma sublobar resection is the appropriate treatment.
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Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Nódulo Pulmonar Solitário/diagnóstico , Nódulo Pulmonar Solitário/terapia , Biópsia por Agulha Fina , Broncoscopia , Humanos , Neoplasias Pulmonares/patologia , Nódulo Pulmonar Solitário/patologiaRESUMO
UNLABELLED: The application of fibrinogen-collagen patch to air tight closure of the lung parenchyma after pulmonary surgery is profitable for the patients but relatively high price of this product may cause a surgeons' hesitation before using it. THE AIM OF THE STUDY: To compare the total costs of treatment of two subgroups of patients in whom, during the same surgical procedure, the fibrinogen-collagen patches were applicated or not to achieve air tight closure of the lung surface. MATERIAL AND METHODS: A total costs of treatment of 122 patients were analyzed. The operations performed were as follows: bullectomy in pulmonary emphysema (n=31), decortication and empyemectomy (n= 16), partial pulmonary resection with coexisting diffuse pleural adhesions (n=75). In 58 patients the surface of the lung was sutured manually or by staplers but in 64 cases fibrinogen-collagen patches were used additionally. RESULTS: The costs of the surgical procedure were higher in the sub-group of patients in whom fibrinogen-collagen patches were applicated. However, in these patients the hospital stay was shorter and the costs of laboratory tests and x-ray examinations performed after surgery were lower in comparison with patients operated on in traditional way. CONCLUSION: Application of a relatively expensive product - fibrinogen-collagen patch to seal the lung parenchyma does not cause the increase of the total cost of the treatment.
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Colágeno/economia , Adesivo Tecidual de Fibrina/economia , Procedimentos Cirúrgicos Pulmonares/economia , Procedimentos Cirúrgicos Pulmonares/métodos , Adulto , Idoso , Feminino , Custos de Cuidados de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , CicatrizaçãoRESUMO
UNLABELLED: Vascular endothelial growth factor (VEGF) is main angiogenic factor, which stimulates endothelial cells migration and proliferation. The extensive angiogenesis plays important role in tumor growth and metastasis. AIM OF THE STUDY: Analysis of serum concentrations of vascular endothelial growth factor in patients with non-small cell lung cancer depending on clinicopathologic findings. MATERIAL AND METHODS: The study group consisted of 50 patients with non-small cell lung cancer (16 females and 34 males) ranging in age from 47 - 80 years (mean age 63 +/- 8.2). Serum VEGF concentration was evaluated by ELISA. RESULTS: VEGF concentrations in serum did not differ significantly between groups of patients with different T-, N- and M-factor. Patients with inoperable tumor (IIIB and IV) had significantly higher serum VEGF concentrations compared with resected tumor (I-IlIA) and locally advanced cancer (IIIA). CONCLUSIONS: Serum VEGF may be a marker of tumor progression in non-small cell lung cancer.
Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Neoplasias Pulmonares/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
UNLABELLED: Matrix metalloproteinases are responsible for the proteolytic degradation of the basement membrane and extracellular matrix. Elevated expression levels of MMP-9 and MMP-2 have been associated with tumor invasion and metastasis. THE AIM OF THIS STUDY: To determine serum concentrations of metalloproteinases 9 and 2 in non-small cell lung cancer patients depending on tumor stage. MATERIAL AND METHODS: The study group consisted of 50 patients with non-small cell lung cancer (16 females and 34 males) ranging in age from 47 - 80 years (mean age 63 +/- 8.2). MMP-9 and MMP-2 concentrations in serum were evaluated by ELISA. RESULTS: MMP-9 and MMP-2 concentrations in serum did not differ significantly between group with different T- and N-factor. Serum level of MMP-9 was significantly higher in patients with metastases than those without them. Patients with inoperable tumor (IIIB - IV) had significantly higher serum MMP-9 concentrations compared with resected tumor (I - IlIA). CONCLUSIONS: Serum MMP-9 may be a marker of metastasis in non-small cell lung cancer.