Browsing by Author "Marić, Dragana (57196811444)"

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. © 2025 by the authors.

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. © 2025 by the authors.

Introduction. A possible association between lung cancer and bullous lung disease has been suggested and recently supported by the results of genetic studies. Case report. A previously healthy 43-year-old man, smoker, was diagnosed with bullous lung disease at the age of 31 years. He was followed up for 12 years when lung cancer (adenocarcinoma) was found at the site. In the meantime, he was treated for recurrent respiratory infections. Conclusion. There is the need for active approach in following up the patients with pulmonary bulla for potential development of lung cancer. © 2016, Institut za Vojnomedicinske Naucne Informacije/Documentaciju. All rights reserved.

Coronavirus disease (COVID-19) in immunocompromised patients represents a major challenge for diagnostics, surveillance, and treatment. Some individuals remain SARS-CoV-2 PCR-positive for a prolonged period. The clinical and epidemiological significance of this phenomenon is not well understood. We report a case of a patient with a history of systemic lupus erythematosus (SLE) who has been persistently SARS-CoV-2 PCR positive for 9 months, with multiple thromboembolic complications, and development of nocardial brain abscess successfully treated with surgery and antibiotics. Copyright © 2022 Veličković, Vukičević, Spurnić, Lazić, Popović, Bogdanović, Raičević, Marić and Berisavac.

Introduction Lung cancer is the leading cause of death from malignancy in Serbia. Objective This is a retrospective analysis of lung cancer epidemiological changes regarding to its histological type and patients' age of both genders. Data were based on surgically treated lung cancer patients from 1985 to 2005. Methods Data were collected from 972 pathohistological reports of operated patients of both genders divided into age groups. Histological types of lung cancer were distributed in four major groups: squamous cell cancer (SCC), adenocarcinoma (AC), small cell cancer (SCLC) and other rare histological types. Both genders together and separately were analysed. Chi-square with the level of significance p<0.05 and chi-square test for trends were used as statistical methods. Results SCC predominated in both genders; in 44.7% females and 68.0% males. AC was less frequently diagnosed (21.8%) than SCC (64.0%) in both genders and all age groups. The most frequently operated patients were aged between 51 and 60 years (36.6%) with SCC and AC predominance. Three patients with SCLC were operated in 61-70 age-group. In age-group up to 30 years, three (0.5%) patients were operated on for SCC and other rare lung tumours, respectively. Predominance of other rare lung tumours was established in 51-60 age-group, 25% of patients of both genders. Conclusion SCC is the most frequent histological type of lung cancer found in all age groups and in both genders of surgically treated patients.

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. © 2024 by the authors.

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. © 2024 by the authors.

Legionella pneumophila is a rarely diagnosed microorganism in Serbia. It causes legionellosis, usually a mild respiratory infection. However, in some cases it can be severe and even life threatening. In June 2020, during the COVID-19 pandemic, a patient with symptoms of the aforesaid infection, namely severe pneumonia and acute respiratory distress syndrome, was admitted to the hospital. The multiplex polymerase chain reaction (PCR) test (The BioFire FilmArray Pneumonia Panel plus) detected the presence of L. pneumophila in the patient’s bronchial secretions. The specific culture for the detection of that organism, however, remained sterile. The patient’s paired sera had been sent for serology and the results in both of them came back positive for Legionella spp. 1–6, while the assays specific for each one of the 10 serogroups detected more than a fourfold increase of antibody titers in an uncommon serogroup 2 only. The patient was treated with moxifloxacin; he recovered well and was discharged after 26 days of hospitalization. Having being diagnosed with the L. pneumophila infection correctly through the multiplex PCR test, the patient was given the right therapy with moxifloxacin. The serologic assays corroborated this result and revealed the uncommon group 2, thus confirming the necessity of carrying out all the tests available to attain the exact diagnosis of legionellosis. © The Author(s) 2022.

Legionella pneumophila is a rarely diagnosed microorganism in Serbia. It causes legionellosis, usually a mild respiratory infection. However, in some cases it can be severe and even life threatening. In June 2020, during the COVID-19 pandemic, a patient with symptoms of the aforesaid infection, namely severe pneumonia and acute respiratory distress syndrome, was admitted to the hospital. The multiplex polymerase chain reaction (PCR) test (The BioFire FilmArray Pneumonia Panel plus) detected the presence of L. pneumophila in the patient’s bronchial secretions. The specific culture for the detection of that organism, however, remained sterile. The patient’s paired sera had been sent for serology and the results in both of them came back positive for Legionella spp. 1–6, while the assays specific for each one of the 10 serogroups detected more than a fourfold increase of antibody titers in an uncommon serogroup 2 only. The patient was treated with moxifloxacin; he recovered well and was discharged after 26 days of hospitalization. Having being diagnosed with the L. pneumophila infection correctly through the multiplex PCR test, the patient was given the right therapy with moxifloxacin. The serologic assays corroborated this result and revealed the uncommon group 2, thus confirming the necessity of carrying out all the tests available to attain the exact diagnosis of legionellosis. © The Author(s) 2022.