Lung cancer remains the leading cause of cancer death globally, with non-small cell lung cancer (NSCLC) accounting for the majority of cases. Multidrug resistance (MDR), often caused by ATP-binding cassette (ABC) transporters, represents a significant obstacle in the treatment of NSCLC. While genetic profiling has an important role in personalized therapy, functional assays that measure cellular responses to drugs are gaining in importance. We developed an automated microplate-based immunofluorescence assay for the evaluation of MDR markers ABCB1, ABCC1, and ABCG2 in cells obtained from NSCLC patients through high-content imaging and image analysis, as part of a functional diagnostic approach. This assay effectively discriminated cancer from non-cancer cells within mixed cultures, which is vital for accurate assessment of changes in MDR marker expression in different cell populations in response to anticancer drugs. Validation was performed using established drug-sensitive (NCI-H460) and drug-resistant (NCI-H460/R) NSCLC cell lines, demonstrating the assay’s capacity to distinguish and evaluate different MDR profiles. The obtained results revealed wide-ranging effects of various chemotherapeutic agents on MDR marker expression in different patient-derived NSCLC cultures, emphasizing the need for MDR diagnostics in NSCLC. In addition to being a valuable tool for assessing drug effects on MDR markers in different cell populations, the assay can complement genetic profiling to optimize treatment. Further assay adaptations may extend its application to other cancer types, improving treatment efficacy while minimizing the development of resistance.

Background and Objectives: Death is an unavoidable experience in any person’s life and affects not only the dying person but also their caregivers. The dying process has been displaced from homes to health care facilities in the majority of cases. Facing death and dying has become an everyday life of health care professionals (HCP), especially in palliative care (PC) settings. This study aimed to investigate the death attitudes among HCPs in Serbia. Materials and Methods: The Serbian version of the Death Attitude Profile-Revised (DAP-RSp) was used as a measurement instrument. Results: The average age of the 180 included participants was 42.2 ± 9.9 years; the majority were females (70.0%), with more than 10 years of working experience (73.0%), physicians (70.0%) and those working in a non-oncological (non-ONC) field (57.78%). The mean total score of DAP-RSp was 124.80 ± 22.44. The highest mean score was observed in the neutral acceptance dimension (NA) (5.82 ± 0.90) and lowest in the Escape acceptance (EA) (2.57 ± 1.21). Higher negative death attitudes were reported among nurses compared to physicians (p = 0.002). Statistically significant differences were observed in the fear of death (FD) and death avoidance (DA) domains, favoring PC specialists and oncologists (p = 0.004; p = 0.015). Physicians working in Oncology (ONC) showed lower FD values (p = 0.001) compared to non-ONC departments. Conclusions: Attitudes toward death among HCPs are of great importance for the well-being of both HCPs and patients. Negative attitudes can lead to deficient care. The fear of death is highly represented among Serbian HCPs working in non-ONC fields, including both nurses and physicians. This study emphasizes the need for further research to comprehensively explore and understand HCPs’ attitudes toward death. This research highlights the need for the development of an educational curriculum across all levels of medical education, aimed at overcoming the fear of death and enhancing coping strategies, which will improve the care for patients diagnosed with terminal illnesses.

The impact of tyrosine kinase inhibitors (TKIs) on multidrug resistance (MDR) in non-small cell lung carcinoma (NSCLC) is a critical aspect of cancer therapy. While TKIs effectively target specific signaling pathways of cancer cells, they can also act as substrates for ABC transporters, potentially triggering MDR. The aim of our study was to evaluate the response of 17 patient-derived NSCLC cultures to 10 commonly prescribed TKIs and to correlate these responses with patient mutational profiles. Using an ex vivo immunofluorescence assay, we analyzed the expression of the MDR markers ABCB1, ABCC1, and ABCG2, and correlated these data with the genetic profiles of patients for a functional diagnostic approach. NSCLC cultures responded differently to TKIs, with erlotinib showing good efficacy regardless of mutation burden or EGFR status. However, the modulation of MDR mechanisms by erlotinib, such as increased ABCG2 expression, highlights the challenges associated with erlotinib treatment. Other TKIs showed limited efficacy, highlighting the variability of response in NSCLC. Genetic alterations in signaling pathways associated with drug resistance and sensitivity, including TP53 mutations, likely contributed to the variable responses to TKIs. The relationships between ABC transporter expression, gene alterations, and response to TKIs did not show consistent patterns. Our results suggest that in addition to mutational status, performing functional sensitivity screening is critical for identifying appropriate treatment strategies with TKIs. These results underscore the importance of considering drug sensitivity, off-target effects, MDR risks, and patient-specific genetic profiles when optimizing NSCLC treatment and highlight the potential for personalized approaches, especially in early stages.

Introduction: Lung cancer remains the leading cause of cancer death among all cancers. The discovery of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations led to an increased survival rate in patients with locally advanced and metastatic non-small cell lung cancer (NSCLC). Results of the ALTA 1L study showed superior outcomes for patients treated with brigatinib compared to patients treated with crizotinib. Background: We conducted research including 23 patients with ALK-positive lung adenocarcinoma who were treated with brigatinib in first or further lines of therapy. The median follow-up was 22 months (4–66 months). Results: There were no significant differences in patient population between the first and further lines of treatment regarding sex distribution (p = 0.692), smoking status (p = 0.554), ECOG performance status (p = 1.000), and baseline presence of brain metastases (p = 0.862). The response rate was 47.8%, and disease control was 95.6%. The 12-month progression-free survival (PFS) and overall survival (OS) rates were 85.3% and 86.5%, respectively, while the 60-month PFS rate was not reached, and the 60-month OS rate was 27.1%. The mPFS and mOS were 32 months. Conclusions: The results of this analysis are promising, as our patients experienced better outcomes compared to those in the ALTA 1L study, which may be attributed to the small sample size. However, the effectiveness of brigatinib has been confirmed in our clinical practice.

Background/Objectives: Non-small cell lung carcinoma (NSCLC) is characterized by its diverse molecular profiles and varying responses to treatment, highlighting the importance of precision medicine in optimizing therapeutic outcomes. A promising approach involves using patient-derived cellular models, which provide insights into the unique biology of individual tumors and their responsiveness to treatment. Methods: We established short-term primary cell cultures from thirteen patients with NSCLC of different subtypes and stages, including both cancer and stromal cells. To evaluate the ex vivo cytotoxicity and selectivity of eight chemotherapeutics and erlotinib, we employed an immunoassay, and the results were analyzed using an automated imaging system. Scoring of the obtained results was also performed. The ex vivo responses to cisplatin, etoposide, and paclitaxel were correlated with the patients’ responses to therapy. We used Kaplan–Meier analysis to assess progression-free survival (PFS) differences among patient groups. Results: NSCLC cells exhibited significant variability in their responses to drugs, with stromal cells demonstrating greater sensitivity. Tumors at stages I-III responded to multiple treatments, whereas stage IV cells showed considerable resistance. Erlotinib effectively reduced cancer cell growth at lower doses but plateaued at higher concentrations. The immunoassay indicated 67% sensitivity and 100% specificity in predicting patient responses to chemotherapy. Sensitivity to etoposide and paclitaxel correlated with progression-free survival (PFS). Conclusions: A personalized treatment strategy, such as our immunoassay based on the ex vivo responses of cancer patients’ cells, can guide treatment decisions and, in some cases, serve as surrogate biomarkers for tumor types that lack actionable biomarkers.

Aspiration-inhalation of solid or liquid materials into the airways-occurs when solids or liquids are introduced into the supraglottic area rapidly or in large volumes or when airway defences are reduced by structural abnormalities or neurological impairment. Tracheobronchial aspiration (TBA) syndrome is currently among leading causes of morbidity and mortality in the world when it comes to accidents, and it is the leading cause in one-year-old children. During the last several years, destructive effects of some food and drugs on respiratory system have been revealed. TBA may cause no complications at all or may result in a range of complications from paroxysmal cough to respiratory failure and lethal outcome. Rapid diagnosis is of utmost importance in correct interventions that should be done in a timely manner, and in prevention of complications, which are sometimes irreversible. This is a review of TBA syndrome etiopathogenesis with special reference to those caused by solid foreign bodies, including those of biological origin, hydrocarbons, lipids, and water-drowning. Special attention is given to TBA syndrome in children, and to complications such as aspiration pneumonia and pneumonitis. Current approach in treatment of the syndrome is explained in dependence of its etiology. Importance, indications and possibilities of interventional bronchoscopy are highlighted.