Non-small cell lung cancer (NSCLC) is largely promoted by a multistep tumorigenesis process involving various genetic and epigenetic alterations, which essentially contribute to the high incidence of mortality among patients with NSCLC. Clinical observations revealed that NSCLC also co-opts a multifaceted immune checkpoint dysregulation as an important driving factor in NSCLC progression and development. For example, a deregulated PI3K/AKT/mTOR pathway has been noticed in 50-70% of NSCLC cases, primarily modulated by mutations in key oncogenes such as ALK, EGFR, KRAS, and others. Additionally, genetic association studies containing patient-specific factors and local reimbursement criteria expose/reveal mutations in EGFR/ALK/ROS/BRAF/KRAS/PD-L1 proteins to determine the suitability of available immunotherapy or tyrosine kinase inhibitor therapy. Thus, the expression of such checkpoints on tumors and immune cells is pivotal in understanding the therapeutic efficacy and has been extensively studied for NSCLC treatments. Therefore, this review summarizes current knowledge in NSCLC tumorigenesis, focusing on its genetic and epigenetic intricacies, immune checkpoint dysregulation, and the evolving landscape of targeted therapies. In the context of current and future therapies, we emphasize the significance of antibodies targeting PD-1/PD-L1 and CTLA-4 interactions as the primary therapeutic strategy for immune system reactivation in NSCLC. Other approaches involving the promising potential of nanobodies, probodies, affibodies, and DARPINs targeting immune checkpoints are also described; these are under active research or clinical trials to mediate immune regulation and reduce cancer progression. This comprehensive review underscores the multifaceted nature, current state and future directions of NSCLC research and treatment.
- MeSH
- antigeny CD274 metabolismus MeSH
- erbB receptory metabolismus MeSH
- fosfatidylinositol-3-kinasy metabolismus MeSH
- karcinogeneze MeSH
- lidé MeSH
- nádorová transformace buněk MeSH
- nádory plic * farmakoterapie genetika MeSH
- nemalobuněčný karcinom plic * farmakoterapie genetika MeSH
- protoonkogenní proteiny p21(ras) MeSH
- tyrosinkinasové receptory metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
RATIONALE: Persistent respiratory symptoms following Coronavirus Disease 2019 (COVID-19) are associated with residual radiological changes in lung parenchyma, with a risk of development into lung fibrosis, and with impaired pulmonary function. Previous studies hinted at the possible efficacy of corticosteroids (CS) in facilitating the resolution of post-COVID residual changes in the lungs, but the available data is limited. AIM: To evaluate the effects of CS treatment in post-COVID respiratory syndrome patients. PATIENTS AND METHODS: Post-COVID patients were recruited into a prospective single-center observational study and scheduled for an initial (V1) and follow-up visit (V2) at the Department of Respiratory Medicine and Tuberculosis, University Hospital Olomouc, comprising of pulmonary function testing, chest x-ray, and complex clinical examination. The decision to administer CS or maintain watchful waiting (WW) was in line with Czech national guidelines. RESULTS: The study involved 2729 COVID-19 survivors (45.7% male; mean age: 54.6). From 2026 patients with complete V1 data, 131 patients were indicated for CS therapy. These patients showed significantly worse radiological and functional impairment at V1. Mean initial dose was 27.6 mg (SD ± 10,64), and the mean duration of CS therapy was 13.3 weeks (SD ± 10,06). Following therapy, significantly better improvement of static lung volumes and transfer factor for carbon monoxide (DLCO), and significantly better rates of good or complete radiological and subjective improvement were observed in the CS group compared to controls with available follow-up data (n = 894). CONCLUSION: Better improvement of pulmonary function, radiological findings and subjective symptoms were observed in patients CS compared to watchful waiting. Our findings suggest that glucocorticoid therapy could benefit selected patients with persistent dyspnea, significant radiological changes, and decreased DLCO.
- Publikační typ
- časopisecké články MeSH
Lung malignancies have a substantial impact on cancer incidence and mortality worldwide. Even though many factors involved in the development of the disease are known, many questions remain unanswered. Previous studies suggest that the intestinal microbiota may have a role in developing malignant diseases. According to some findings, the microbiota has proven to be a key modulator of carcinogenic processes and the immune response against cancer cells, potentially influencing the effectiveness of immunotherapy. In our study, we characterized culturable microorganisms associated with non-small cell lung cancer (NSCLC) that can be recovered from rectal swabs and mouthwash. In addition, we also explored differences in the culturable microbiota with two main types of NSCLC - adenocarcinoma (ADC) and squamous cell carcinoma (SCC). With 141 patients included in the study (86 ADC and 55 SCC cases), a significant difference was observed between the two types in seven bacterial species (Collinsella, Corynebacterium, Klebsiella, Lactobacillus, Neisseria, Rothia, and Streptococcus), including the site of origin. The relationship between microbial dysbiosis and lung cancer is poorly understood; future research could shed light on the links between gut microbiota and lung cancer development.
- MeSH
- adenokarcinom * MeSH
- lidé MeSH
- mikrobiota * MeSH
- nádory plic * mikrobiologie patologie MeSH
- nemalobuněčný karcinom plic * mikrobiologie patologie MeSH
- spinocelulární karcinom * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
There have been studies on antibiotic use concerning lung cancer and its potential impact on carcinogenesis and microbiome. However, subsequent research has failed to support these associations consistently. In terms of the potential carcinogenic of antibiotics on lung cancer, the available evidence has not been sufficient to draw any definitive conclusions. Maintaining immune homeostasis and preventing pathogen invasion is critically dependent on the microbiome. The subtle balance of the body microbiota, including the lungs, is susceptible to disruption by antibiotic use. There is an association between disruptions of the lung microbiome and respiratory diseases, including lung cancer, and decreased efficacy of treatments. Patients with lung cancer are often indicated for antibiotic treatment due to respiratory infections or other comorbidities. Pulmonary infections in the area of undetected lung tumors are not uncommon. They can be an early sign of malignancy, which may explain the association between antibiotic use and lung cancer diagnosis. Antibiotic use can also affect the effectiveness of immune checkpoint inhibitor therapy. Studies suggest that antibiotic use can impair the efficacy of immune checkpoint inhibitor therapy in lung cancer patients, particularly around the time when treatment is initiated. These findings require further study, understanding underlying mechanisms, and identifying microbiota signatures associated with treatment response.
Následující kazuistické sdělení popisuje dva případy pacientek ukrajinské národnosti, které byly došetřovány pro respirační potíže. V prvním kazuistickém případě byla diagnostikována pneumocystová pneumonie (PCP) v rámci pokročilé HIV infekce ve stadiu AIDS. U druhé nemocné byla diagnostikována koincidence TBC plic, kvasinkové laryngotracheitidy, virové hepatitidy C a HIV infekce. V případě pacientů pocházejících ze zemí s vyšší incidencí HIV a tuberkulózy (TBC) je nutno v rámci diferenciální diagnostiky pomýšlet na tyto možné příčiny potíží. Tyto přenosné infekce jsou rizikem nejenom pro samotného pacienta, ale i pro okolní společnost.
The presented case report describes two cases of Ukrainian patients who underwent a follow-up examination for respiratory difficulties. In the first reported case, the patient was diagnosed with pneumocystic pneumonia (PCP) as a part of advanced HIV infection in the AIDS stage. The second patient was diagnosed with coincidence of pulmonary tuberculosis, yeast laryngotracheitis, viral hepatitis C and HIV infection. In the case of patients from countries with a higher incidence of HIV and tuberculosis (TBC), it is necessary to consider these possible causes of problems as part of the differential diagnosis. These transmissible infections are a risk not only for the patients themselves, but also for the surrounding society.
Transplantace je poslední možností léčby u terminálních stadií řady plicních nemocí. Jednou z limitací dlouhodobé prognózy pacientů je rejekce štěpu. Některé faktory vzniku a progrese odmítnutí transplantátu jsou známy a lze je léčebně ovlivnit. Poznatky z recentních studií odhalují, že jedním z dosud přehlížených faktorů může být také znečištění ovzduší. Článek shrnuje aktuální poznatky o vlivu chronické expozice inhalačním noxám na pacienty po plicní transplantaci, a to zejména s ohledem na vznik rejekce štěpu.
AIMS: The study analysed post-acute COVID-19 symptoms and the pulmonary function test (PFT) results in patients surviving the native strain of the virus. METHODS: The study was prospective; the inclusion criteria were positive PCR test for SARS-CoV-2 and age 18-100. Exclusion criteria were active respiratory infection, known or suspicious pre-existing pulmonary disease, cardiac failure, recent or acute pulmonary embolism, anaemia, and neuromuscular diseases. The recruitment period was 1st March 2020 - 25th December 2020. The initial examination was performed 4-12 weeks after the disease onset. All subjects underwent physical examination, anamnesis, chest x-ray and PFT. RESULTS: The study involved 785 subjects (345 male) mean age 53.8 (SD 14.6). The disease severity groups were: mild (G1), moderate (G2) and severe/critical (G3). Anosmia was present in the acute disease phase in 45.2% of G1 patients, but only in 4.5% of G3 patients. Dyspnoea occurred frequently in more severe groups (40%, 51.8% and 63.7% for G1, G2 and G3 respectively), while cough and fatigue showed no relationship to disease severity. Females were more likely to experience persistent symptoms. PFT results were significantly decreased in more severe groups compared to the mild COVID-19 patients, diffusing capacity was 86.3%, 79% and 68% of predicted values in G1, G2 and G3 respectively. CONCLUSION: Anosmia during the acute phase was associated with mild disease, persisting dyspnoea was more frequent after more severe COVID-19. Females tended to have persisting symptoms in post-acute phase more frequently. PFT results showed decrease with disease severity.
- MeSH
- anosmie MeSH
- COVID-19 * komplikace diagnóza MeSH
- dospělí MeSH
- dyspnoe etiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- prospektivní studie MeSH
- respirační funkční testy MeSH
- SARS-CoV-2 MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
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Sarcoidosis is a heterogenous, multisystemic inflammatory disease that primarily affects lungs. In this study, we multiplex genotyped 18 single-nucleotide polymorphisms (SNPs) to replicate the findings from previous genome-wide association studies (GWAS) and candidate gene studies, and extended analyses to different clinical manifestations (Löfgren's syndrome and chest X-ray [CXR] stages) including treatment response among West-Slavonic subjects (564 sarcoidosis patients and 301 healthy controls). We confirm the replication (with Bonferroni's correction) of ANXA11 rs1049550 as protective variant for sarcoidosis (odds ratio [OR] = 0.71, p = 1.33 × 10-3), non-LS (OR = 0.66, p = 2.71 × 10-4) and CXR stages 2-4 (OR = 0.62, p = 7.48 × 10-5) compared to controls in West-Slavonic population. We also validate the association of risk variants C6orf10 rs3129927 (OR = 2.61, p = 2.60 × 10-8), TNFA rs1800629 (OR = 1.56, p = 6.65 × 10-4), ATF6B rs3130288 (OR = 2.75, p = 1.06 × 10-9) and HLA-DQA1 rs2187668 (OR = 1.74, p = 8.83 × 10-4) with sarcoidosis compared to controls. For sub-phenotypes compared to controls, risk variants C6orf10 rs3129927 (OR = 5.35, p = 1.07 × 10-12), TNFA rs1800629 (OR = 2.66, p = 5.94 × 10-7), ATF6B rs3130288 (OR = 5.24, p = 5.21 × 10-13), LRRC16A rs9295661 (OR = 2.97, p = 4.29 × 10-4), HLA-DQA1 rs2187668 (OR = 3.14, p = 1.09 × 10-6) and HLA-DRA rs3135394 (OR = 5.23, p = 8.25 × 10-13) were associated with LS while C6orf10 rs3129927 (OR = 1.96, p = 4.27 × 10-4) and ATF6B rs3130288 (OR = 2.15, p = 3.36 × 10-5) were associated with non-LS. For CXR stages compared to controls, C6orf10 rs3129927 (OR = 3.67, p = 3.63 × 10-11), TNFA rs1800629 (OR = 1.84, p = 1.32 × 10-4), ATF6B rs3129927 (OR = 3.63, p = 1.82 × 10-11), HLA-DQA1 rs2187668 (OR = 2.13, p = 9.59 × 10-5) and HLA-DRA rs3135394 (OR = 3.42, p = 3.45 × 10-10) were risk variants for early CXR stages 0-1 while C6orf10 rs3129927 (OR = 1.99, p = 5.51 × 10-4), ATF6B rs3129927 (OR = 2.23, p = 3.52 × 10-5) and HLA-DRA rs3135394 (OR = 1.85, p = 2.00 × 10-3) were risk variants for advanced CXR stages 2-4. The present findings nominate gene variants as plausible prognostic markers for clinical phenotypes, treatment response and disease resolution/progression and may form the basis for establishing genotype-phenotype relationships in patients with sarcoidosis among West-Slavonic population.
