Browsing by Author "Kontic, Milica (43761339600)"

[No abstract available]

[No abstract available]

Objective The aim of this study was to analyse prevalence and type of pulmonary manifestations in patients with primary antiphospholipid syndrome (PAPS), their association to antiphospholipid antibody (aPL) type and localisation of peripheral vascular thrombosis, and possible relationship to existing cardiac manifestations. Methods Our cross-sectional study comprised 318 PAPS patients, enrolled in the study as the Serbian APS Registry. aPL analysis included detection of aCL (IgG/IgM), β2GPI (IgG/IgM) and LA, served to evaluate associations with cardiac and pulmonary manifestations. Results In patients with pulmonary embolism and infarction, we observed significant prevalence of myocardial infarction (p=0.044), unstable angina pectoris (p=0.001), venous thrombosis (p=0.007) arterial thrombosis (p=0.0001), deep venous thrombosis of the low extremities (p=0.008), and superficial thrombophlebitis of the low extremities (p=0.023). Patients with primary pulmonary hypertension were more prone to unstable angina pectoris (p=0.009), while patients with secondary pulmonary hypertension were more prone to venous thrombosis (p=0.04) and deep venous thrombosis of the inferior extremities (p=0.04). Patients with pulmonary microthrombosis were more prone to unstable angina pectoris (p=0.026), arterial thrombosis (p=0.002), venous thrombosis (p=0.001), deep venous thrombosis of the inferior extremities (p=0.001), and superficial thrombophlebitis of the inferior extremities (p=0.001). The presence of LA was significantly higher in patients with pulmonary embolism and infarction (p=0.001), secondary pulmonary hypertension (p=0.032), and pulmonary microthrombosis (p=0.001). Conclusion Presence of LA was associated with distinct pulmonary manifestations in the Serbian APS cohort. There is a strong link between some cardiovascular and pulmonary manifestations in PAPS patients, suggesting complexity and evolutionary nature of PAPS. © Clinical and Experimental Rheumatology 2015.

Objective The aim of this study was to analyse prevalence and type of pulmonary manifestations in patients with primary antiphospholipid syndrome (PAPS), their association to antiphospholipid antibody (aPL) type and localisation of peripheral vascular thrombosis, and possible relationship to existing cardiac manifestations. Methods Our cross-sectional study comprised 318 PAPS patients, enrolled in the study as the Serbian APS Registry. aPL analysis included detection of aCL (IgG/IgM), β2GPI (IgG/IgM) and LA, served to evaluate associations with cardiac and pulmonary manifestations. Results In patients with pulmonary embolism and infarction, we observed significant prevalence of myocardial infarction (p=0.044), unstable angina pectoris (p=0.001), venous thrombosis (p=0.007) arterial thrombosis (p=0.0001), deep venous thrombosis of the low extremities (p=0.008), and superficial thrombophlebitis of the low extremities (p=0.023). Patients with primary pulmonary hypertension were more prone to unstable angina pectoris (p=0.009), while patients with secondary pulmonary hypertension were more prone to venous thrombosis (p=0.04) and deep venous thrombosis of the inferior extremities (p=0.04). Patients with pulmonary microthrombosis were more prone to unstable angina pectoris (p=0.026), arterial thrombosis (p=0.002), venous thrombosis (p=0.001), deep venous thrombosis of the inferior extremities (p=0.001), and superficial thrombophlebitis of the inferior extremities (p=0.001). The presence of LA was significantly higher in patients with pulmonary embolism and infarction (p=0.001), secondary pulmonary hypertension (p=0.032), and pulmonary microthrombosis (p=0.001). Conclusion Presence of LA was associated with distinct pulmonary manifestations in the Serbian APS cohort. There is a strong link between some cardiovascular and pulmonary manifestations in PAPS patients, suggesting complexity and evolutionary nature of PAPS. © Clinical and Experimental Rheumatology 2015.

The aim of this study was to investigate association between pulmonary and skin manifestations in a large group of patients with primary antiphospholipid syndrome (PAPS) as well as their connection with antiphospholipid antibodies. Methods Our prospective study comprises of 390 patients with primary APS. Antiphospholipid antibody (aPL) analysis included detection of aCL (IgG/IgM), β2GPI (IgG/IgM) and LA. Distinct pulmonary and skin associations were determined, as well as their associations with aPL. Results In PAPS patients the presence of LA was more common in PTE (p=0.005) and in pulmonary microthrombosis (p=0.003). We revealed statistical significance considering the presence of aCL IgM and pulmonary microthrombosis (p=0.05). Skin ulcerations correlated with positive titres aCL IgM and ß2 GPI IgM (p=0.03 and 0.04, respectively), while pseudovasculitis correlated with positive titres ß2 GPI IgM (p=0.02). PAPS patients were more more likely to develop pulmonary thromboembolisam if they had livedo reticularis (p=0.005), skin ulcerations (p=0.007), pseudovasculitic lesions (p=0.01), superficial cutaneous necrosis (p=0.005), and digital gangrene (p=0.02). Patients were also more prone to pulmonary microthrombosis if they already had livedo reticularis (p=0.03), skin ulcerations (p=0.007), pseudovasculitic lesions (p=0.05), superficial cutaneous necrosis (p=0.006), and digital gangrene (p=0.02). Conclusion There is strong link between some pulmonary and skin manifestations in PAPS patients, suggesting complexity and evolutionary nature of APS. The presence of skin manifestations may be a high risk factor for several types of serious pulmonary manifestations in PAPS. Certain aPL types are associated with distinct pulmonary and skin manifestation, suggesting their predictive role. © Clinical and Experimental Rheumatology 2018.

The aim of this study was to investigate association between pulmonary and skin manifestations in a large group of patients with primary antiphospholipid syndrome (PAPS) as well as their connection with antiphospholipid antibodies. Methods Our prospective study comprises of 390 patients with primary APS. Antiphospholipid antibody (aPL) analysis included detection of aCL (IgG/IgM), β2GPI (IgG/IgM) and LA. Distinct pulmonary and skin associations were determined, as well as their associations with aPL. Results In PAPS patients the presence of LA was more common in PTE (p=0.005) and in pulmonary microthrombosis (p=0.003). We revealed statistical significance considering the presence of aCL IgM and pulmonary microthrombosis (p=0.05). Skin ulcerations correlated with positive titres aCL IgM and ß2 GPI IgM (p=0.03 and 0.04, respectively), while pseudovasculitis correlated with positive titres ß2 GPI IgM (p=0.02). PAPS patients were more more likely to develop pulmonary thromboembolisam if they had livedo reticularis (p=0.005), skin ulcerations (p=0.007), pseudovasculitic lesions (p=0.01), superficial cutaneous necrosis (p=0.005), and digital gangrene (p=0.02). Patients were also more prone to pulmonary microthrombosis if they already had livedo reticularis (p=0.03), skin ulcerations (p=0.007), pseudovasculitic lesions (p=0.05), superficial cutaneous necrosis (p=0.006), and digital gangrene (p=0.02). Conclusion There is strong link between some pulmonary and skin manifestations in PAPS patients, suggesting complexity and evolutionary nature of APS. The presence of skin manifestations may be a high risk factor for several types of serious pulmonary manifestations in PAPS. Certain aPL types are associated with distinct pulmonary and skin manifestation, suggesting their predictive role. © Clinical and Experimental Rheumatology 2018.

• PDL1 expression is a widely used biomarker in selecting patients suitable for immunotherapy. • PDL1 expression over 50% is considered a good predictive biomarker in patients with NSCLC. • New guidelines recommend combination immune and chemotherapy as first line treatment in patients with PDL1 over 1% (including patients with TPS over 50%). • Stratification of patients over 50% of PDL1 expression and response to treatment has not been done. • In our study we showed that very high PDL1 expression (over 80%) is a good predictive biomarker for response to ICI. • Several studies confirmed our results with a relatively small sample size, therefore this could be the guideline for future studies. • Would patients with TPS over 80% benefit more from mono immunotherapy, and patients under that mark from combination immune and chemotherapy? © 2023 Elsevier Inc.

• PDL1 expression is a widely used biomarker in selecting patients suitable for immunotherapy. • PDL1 expression over 50% is considered a good predictive biomarker in patients with NSCLC. • New guidelines recommend combination immune and chemotherapy as first line treatment in patients with PDL1 over 1% (including patients with TPS over 50%). • Stratification of patients over 50% of PDL1 expression and response to treatment has not been done. • In our study we showed that very high PDL1 expression (over 80%) is a good predictive biomarker for response to ICI. • Several studies confirmed our results with a relatively small sample size, therefore this could be the guideline for future studies. • Would patients with TPS over 80% benefit more from mono immunotherapy, and patients under that mark from combination immune and chemotherapy? © 2023 Elsevier Inc.

[No abstract available]

Background: In spite of the progress made in neoadjuvant therapy for operable non small-cell lung cancer (NSCLC), many issues remain unsolved, especially in locally advanced stage IIIA. Methods: Retrospective data of 163 patients diagnosed with stage IIIA NSCLC after surgery was analyzed. The patients were divided into two groups: a preoperative chemotherapy group including 59 patients who received platinum-etoposide doublet treatment before surgery, and an upfront surgery group including 104 patients for whom surgical resection was the first treatment step. Adjuvant chemotherapy or/and radiotherapy was administered to 139 patients (85.3%), while 24 patients (14.7%) were followed-up only. Results: The rate of N2 disease was significantly higher in the upfront surgery group (P < 0.001). The one-year relapse rate was 49.5% in the preoperative chemotherapy group compared to 65.4% in the upfront surgery group. There was a significant difference in relapse rate in relation to adjuvant chemotheraphy treatment (P = 0.007). The probability of relapse was equal whether radiotherapy was applied or not (P = 0.142). There was no statistically significant difference in two-year mortality (P = 0.577). The median survival duration after two years of follow-up was 19.6 months in the preoperative chemotherapy group versus 18.8 months in the upfront surgery group (P = 0.608 > 0.05). Conclusion: There was significant difference in preoperative chemotherapy group regarding relapse rate and treatment outcomes related to the lymph node status comparing to the upfront surgery group. Neoadjuvant/adjuvant chemo-therapy is a part of treatment for patients with stage IIIA NSCLC, but further investigation is required to determine optimal treatment. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd

Objective: To report the first case of concomitant drug-and infection-induced antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) in a patient treated with propylthiouracil (PTU) and suffering from tuberculosis. Presentation and Intervention: A 28-year-old woman with PTU-treated hyperthyroidism presented with fever, purpura, pulmonary cavitations and ANCA to myeloperoxidase, bactericidal/permeability-increasing protein (BPI), proteinase-3 and elastase. Skin histopathology confirmed vasculitis. However, sputum examination revealed Mycobacterium tuberculosis. Remission was achieved after PTU withdrawal and treatment with antituberculosis drugs. Conclusion: Our case confirmed that BPI-ANCA are elevated in active tuberculosis. Multispecific ANCA were helpful for the diagnosis of concomitant PTU-and M. tuberculosis-induced AAV. Copyright © 2012 S. Karger AG, Basel.

The actual nature of spindle cell carcinoma has been debated extensively because of its rarity. It carries a poor prognosis, even when early-stage disease is diagnosed and resected. In view of the rarity and the significance of the histological diagnosis, we report a patient with rapidly progressing spindle cell lung carcinoma with soft tissue metastasis. Diagnosis was confirmed by immunohistochemistry finding. Analysis of the TP53 gene mutations by polymerase chain reaction and DNA sequencing revealed insertion of single thymine resulting in frameshift mutation in the exon 8. Prognosis of spindle cell lung carcinoma might be determined by the sarcoma component of the tumor and, based on that, we wonder if this type of lung carcinoma could be followed-up and treated by strategies for soft tissue sarcomas, because of its rapid, sarcomatous type of growth, beside the properly lung carcinoma oncological treatment. © 2012 Arányi Lajos Foundation.

The actual nature of spindle cell carcinoma has been debated extensively because of its rarity. It carries a poor prognosis, even when early-stage disease is diagnosed and resected. In view of the rarity and the significance of the histological diagnosis, we report a patient with rapidly progressing spindle cell lung carcinoma with soft tissue metastasis. Diagnosis was confirmed by immunohistochemistry finding. Analysis of the TP53 gene mutations by polymerase chain reaction and DNA sequencing revealed insertion of single thymine resulting in frameshift mutation in the exon 8. Prognosis of spindle cell lung carcinoma might be determined by the sarcoma component of the tumor and, based on that, we wonder if this type of lung carcinoma could be followed-up and treated by strategies for soft tissue sarcomas, because of its rapid, sarcomatous type of growth, beside the properly lung carcinoma oncological treatment. © 2012 Arányi Lajos Foundation.

This paper presents a rare case of an elderly patient treated with erlotinib for disseminated lung adenocarcinoma with poor performance status (Eastern Cooperative Oncology Group performance status [PS]3). This treatment led to a long duration of complete remission according to Response Evaluation Criteria in Solid Tumors 1.1 – almost 7 years (81 months) of progression-free survival (PFS) and overall survival (OS) of 10 years by March 2017. The treatment with erlotinib started in September 2008 and it was well tolerated with no adverse effects. Mutation analyses (real-time polymerase chain reaction method) revealed deletion of EGFR (epidermal growth factor receptor) gene and wild-type Kirsten-ras protein gene in exon 19. In May 2015, the patient relapsed with jaundice and enlarged lymph nodes of the liver hilum, with no other metastasis, PS 2. Biopsy confirmed metastasis of lung adenocarcinoma. EGFR molecular testing did not reveal T790M mutation. Treatment was continued with gemcitabine–cisplatin chemotherapy. A total of six cycles were administered with nearly complete response and Eastern Cooperative Oncology Group performance status 0. Further on, gemcitabine monotherapy has been administered with nearly complete response maintained and OS of 10 years by March 2017. This report describes an extremely rare case of a poor performance patient with advanced metastatic adenocarcinoma harboring EGFR mutation – deletion in exon 19 – who was receiving salvage erlotinib and had a complete response with 81 months of PFS followed by a relapse and subsequent chemotherapy which led to nearly complete response, with an OS of 10 years by March 2017. Such a complete response to tyrosine kinase inhibitor therapy in a poor PS patient, with long PFS and OS achieved, justifies tyrosine kinase inhibitor treatment approach in poor PS patients with EGFR-sensitizing tumors, and furthermore points to the feasibility of administering chemotherapy at the time of relapse. © 2017 Jovanovic et al.

The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterations and tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, we conducted pairwise genetic interaction analyses among 35,031 SNPs from 2027 oncogenesis-related genes. The genotypes from three independent genome-wide association studies including a total of 24,037 lung cancer patients and 20,401 healthy controls with Caucasian ancestry were analyzed in the study. Using a two-stage study design including discovery and replication studies, and stringent Bonferroni correction for multiple statistical analysis, we identified significant genetic interactions between SNPs in RGL1:RAD51B (OR=0.44, p value=3.27x10-11 in overall lung cancer and OR=0.41, p value=9.71x10-11 in non-small cell lung cancer), SYNE1:RNF43 (OR=0.73, p value=1.01x10-12 in adenocarcinoma) and FHIT:TSPAN8 (OR=1.82, p value=7.62x10-11 in squamous cell carcinoma) in our analysis. None of these genes have been identified from previous main effect association studies in lung cancer. Further eQTL gene expression analysis in lung tissues provided information supporting the functional role of the identified epistasis in lung tumorigenesis. Gene set enrichment analysis revealed potential pathways and gene networks underlying molecular mechanisms in overall lung cancer as well as histology subtypes development. Our results provide evidence that genetic interactions between oncogenesis-related genes play an important role in lung tumorigenesis and epistasis analysis, combined with functional annotation, provides a valuable tool for uncovering functional novel susceptibility genes that contribute to lung cancer development by interacting with other modifier genes. Copyright: Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Background: Promoter hypermethylation of tumor suppressor genes presents promising markers for lung cancer diagnosis and prognosis. The purpose of this study was to determine the association between the promoter hypermethylation of multiple genes and 5‑year survival rate in patients with Non‑small cell lung cancer (NSCLC). Materials and Methods: Primary tumor samples (n = 65), corresponding nonmalignant lung tissues (n = 65), and circulating blood were obtained from NSCLC patients who underwent curative surgery. Promoter methylation status in seven genes (RASSF1A, CDH13, MGMT, ESR1, DAPK, SOX1, and HOXA9) was quantified by using bisulfite pyrosequencing. Five‑year survival data were obtained by a clinician. Cox proportional hazards models were used to analyze the associations between gene methylation status and overall patient survival. Results: The 5‑year survival of the patients with SOX1 aberrant tumor methylation was found to be statistically significantly shorter than for those patients without aberrant tumor methylation (P = 0.01). This effect was independent of TNM stage. No significant survival differences were associated with aberrant methylation in other genes tested in either of the two tissue types. Conclusion: Our study shows that SOX1 promoter hypermethylation in NSCLC tumors is significantly associated with inferior survival, showing promise as a useful prognostic biomarker in patients with NSCLC. © 2021 Journal of Cancer Research and Therapeutics.

We present a case of large cell lung carcinoma in sixty-one year old male with typical lung cancer symptoms but unusual radiological presentation and immunophenotype. Tumor morphological finding related to its radiological finding was suggestive for large cell lymphoma or carcinoma, but its immunophenotype made confusion for pathological diagnosis. No p53 mutations were detected in genetic investigation. Multidisciplinar diagnostic approach to some tumors is useful for their final diagnosis. © 2010 Arányi Lajos Foundation.

We present a case of large cell lung carcinoma in sixty-one year old male with typical lung cancer symptoms but unusual radiological presentation and immunophenotype. Tumor morphological finding related to its radiological finding was suggestive for large cell lymphoma or carcinoma, but its immunophenotype made confusion for pathological diagnosis. No p53 mutations were detected in genetic investigation. Multidisciplinar diagnostic approach to some tumors is useful for their final diagnosis. © 2010 Arányi Lajos Foundation.

Background: Idiopathic pulmonary fibrosis (IPF) has common risk factors with cancer and significant similarities in the pathobiology process, both diseases having poor outcomes. Immune checkpoint PD-L1 has become the target of checkpoint inhibitory therapy that unleashes antitumor T cells and has revolutionized cancer treatment. This is a pilot study exploring membrane immune checkpoint PD-L1 expression in human IPF lung tissue samples and its soluble form, soluble PD-L1 (sPD-L1) plasma concentrations in IPF patients, in order to investigate potential role of PD-L1 as an IPF biomarker. © Journal of Thoracic Disease. All rights reserved.

The purpose of this work was to identify germ line RB1 mutations in 16 Serbian retinoblastoma patients for genetic counselling. Mutation analysis was carried out by PCR directed sequencing of the 27 exons. Loss of heterozygosity for two RB1 intragenic markers was also analyzed in 14 tumour samples. Five new RB1 oncogenic mutations (g.2078 del C, g.77047_48 del GC, g.78117_8 del TT, g.160797 del T, and g.64439+2 T>C) and two recurrences (R445X and Q383X) have been found in this study. In addition, four intronic variants were observed germ line in some unilateral patients. Two of these variants (g.44668-15T/G, and g.166204-8T/A) are discussed as potential oncogenic mutation candidates. The results show the relevance of studies aimed to investigate the role of intronic variants in exon splicing regulation. Such studies will help to disclose hidden retinoblastoma susceptibilities, important for accurate genetic counselling. © 2006 The Japan Society of Human Genetics and Springer.