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Background. lung cancer is the most common cause of morbidity and mortality among all cancers. The dominant type of lung cancer is non-small cell lung cancer. early diagnosis, rapid and least possible invasive treatment gives the best chance to extend life expectancy. Considering increasing level of NSCLC morbidity it is extremely important to develop cancer diagnostics, which will allow to implement necessary treatment in early stages. Objectives. The main focus of this paper is to establish level of usability for dimeric form of the pyruvate kinase in NSCLC patient plasma using spectrophotometric method. Material and methods. Participants of the study were chosen from patients of the lower silesian lung disease Centre in Wroclaw. Patients were allocated in to two study groups: first containing patients who were diagnosed with adenocarcinoma, second containing patients who were diagnosed with carcinoma planoepitheliale. The control group was chosen from patients who were not diagnosed with cancer. material in question was plasma, tested on pyruvate kinase activity. Results. Analysis showed a difference in pyruvate kinase activity between patients in study groups and test group. The highest increase in enzyme activity was found in group of patients diagnosed with carcinoma planoepitheliale (134.5%). in the group of patients diagnosed with adenocarcinoma enzyme activity increase reached 132.1% and in test group, 116%. Conclusions. Testing enzyme activity of pyruvate kinase can be an additional helpful method in NSCLC diagnoses, besides diagnostic imaging. This method is characterised by high sensitivity and low invasiveness. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinase (MMP)-2 and -9 are gelatinases which are capable of degrading type IV collagen and have been linked to cancer invasion and metastatic development. MMP-2 and MMP-9 gene polymorphisms may affect their biological function, and thus their role in cancer development and progression. We analyzed the association of the polymorphism frequencies of MMP-2-735C/T and MMP-9-1562C/T with MMP-2 and MMP-9 serum concentrations, as well as their potential effects in lung cancer patients. We conducted a retrospective, case-control study consisting of 112 lung cancer patients and 100 healthy individuals from a Caucasian population in Poland. Polymerase chain reaction with restriction fragment length polymorphism (PCR/RFLP) and electrophoresis was used to genotype genomic DNA from whole blood samples. MMP-2 and MMP-9 serum concentrations were then determined using ELISA. For statistical analysis, Statistica version 13 from TIBCO Software Inc. was utilized with a significance level <0.05. Logistic regression analysis revealed that MMP-2-735CC (OR = 5.39; 95% CI = 0.62–47.17; p = 0.238504) and -735CT genotype (OR = 7.22; 95% CI = 0.78–67.14; p = 0.072836), as well as MMP-9-1562CC (OR = 1.45; 95% CI = 0.31–6.70; p = 0.757914) and -1562CT genotype (OR = 1.60; 95% CI = 0.33–7.83; p = 0.548801) were associated with a higher risk of lung cancer. There were statistically significant differences observed in the MMP-2 concentration between individuals with the -735CC genotype and the -735CT genotype (non-smoking control: 204.04 ng/mL vs. 237.00 ng/mL, respectively, p = 0.041479; adenocarcinoma patients: 157.69 ng/mL vs. 126.37 ng/mL, respectively, p = 0.013222), as well as differences in the MMP-9 concentration between individuals with the -1562CC genotype and the -1562CT genotype (smoking control: 385.67 ng/mL vs. 562.80 ng/mL, respectively, p = 0.000936; patients with other lung neoplasms: 821.64 ng/mL vs. 928.88 ng/mL, respectively p = 0.023315). The role of MMP-2-735C/T and MMP-9 -1562C/T polymorphisms in an increased risk of lung cancer cannot be dismissed. Specific genotypes affect MMP-2 and MMP-9 concentrations in both lung cancer patients and healthy controls, which may thereby increase lung cancer risk, disease aggressiveness, and patient survival outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer is the leading cause of cancer-related deaths, with a low overall survival rate. Anaemia is one of the most common cancer side effects, reducing the patient's survival time among other things. Lung cancer patients have the highest incidence of anaemia, with 50–70% of patients experiencing anaemia during the course of their disease. In clinical practice, however, anaemia is not a problem in cancer patients until it becomes severe or life-threatening, at which point therapeutic actions are taken. We choose to change this perception by first investigating the characteristics of proteins involved in the pathogenesis of anaemia, as well as their diagnostic capabilities. We assume that predicting anaemia using diagnostic biomarkers, and thus preventing and treating anaemia in lung cancer patients, is beneficial to both the patient and the economy. We aim to describe the characteristics of hepcidin, IL-6, and TNF-α levels in anaemia of lung cancer patients with operative tumour as well as to investigate the potential diagnostic capabilities of hepcidin in combination with IL-6, TNF-α, and acute phase proteins. We present a retrospective study of 112 lung cancer patients (41 women and 71 men) who were surgically treated at the Lower Silesian Centre for Lung Diseases in Wroclaw, Poland. Serum blood samples were collected from all these patients prior to any surgical treatment and used to determine hepcidin, IL-6, TNF-α, SAA1, and CRP concentrations. Patients were also examined with a complete blood count several times during their hospitalization. The female and male groups were divided based on the occurrence of anaemia during their hospitalization. Patients who developed anaemia post-operatively had significantly lower hepcidin concentrations than non-anaemic patients (p = 0.000694 in females with ≥3 complete blood count examinations and p = 0.007905 in males with 2 complete blood count examinations), whereas patients with anaemia since hospital admission had higher hepcidin concentrations. We observed two hepcidin roles related to two cancer anaemia pathogeneses: (1) higher hepcidin concentrations in patients with anaemia since hospital admission (anaemia of inflammation) and (2) lower hepcidin concentrations in patients who developed anaemia after surgery (anaemia of iron deficiency). Our data support the role of hepcidin, IL-6, and TNF-α in cancer-related anaemia and provide diagnostic values for predicting post-operative anaemia in lung cancer patients. [ABSTRACT FROM AUTHOR]

Rehabilitation may be helpful in the prevention of complications associated with the treatment of patients with pectus excavatum who are subjected to surgery using the Ravitch and Nuss methods. This paper presents the case of a patient who underwent successful physical rehabilitation after 8 weeks from the surgery using the combined method. As part of the Nuss procedure, two plates were implanted to form a scaffolding for the patient's chest, which had previously been corrected with the Ravitch method. The plates were to be removed after 24 months of treatment. After the procedure, in spite of the favorable cosmetic effect of the repair, there was a significant decrease in the spirometric values and physical fitness of the patient. He underwent an individual physiotherapy program, which lasted four weeks. The streamlining of the respiratory system has significantly improved the spirometric values and raised the overall performance of the patient's organism. [ABSTRACT FROM AUTHOR]

Background: The potential involvement of zyxin (ZYX) in carcinogenesis has been investigated in many cancer types. However, there are a limited number of studies on the role of ZYX in the progression of non-small cell lung cancer (NSCLC). Since lung cancer is one of the most frequently diagnosed carcinomas, the aim of our study was to determine the localization and expression levels of ZYX in NSCLC and to correlate the results with the clinicopathological data. Materials and Methods: The expression of ZYX was assessed in NSCLC cases and in cell lines representing this tumor type. Levels of ZYX were determined in the clinical material using immunohistochemistry (IHC) and Western Blot. Real-time PCR was used to assess ZYX mRNA levels. The expression of ZYX was also checked in NSCLC cell lines using real-time PCR, Western Blot, and immunofluorescence/immunocytochemistry. Results: The results showed lower levels of ZYX in NSCLC cells compared with control tissues. This trend was observed at the protein and mRNA levels. The assays on the NSCLC model also demonstrated lower levels of ZYX in cancer cells compared with control cells. Conclusions: The decreased expression of ZYX in NSCLC may indicate a suppressor role of this protein in NSCLC. [ABSTRACT FROM AUTHOR]

Recently a gluconeogenic enzyme was discovered-fructose 1,6-bisphosphatase (FBPase)-that localizes in the nucleus of a proliferating cell, but its physiological role in this compartment remains unclear. Here, we demonstrate the link between nuclear localization of FBPase and the cell cycle progression. Results of our studies indicate that in human and mouse squamous cell lung cancer, as well as in the HL-1 cardiomyocytes, FBPase nuclear localization correlates with nuclear localization of S and G2 phase cyclins. Additionally, activity and expression of the enzyme depends on cell cycle stages. Identification of FBPase interacting partners with mass spectrometry reveals a set of nuclear proteins involved in cell cycle regulation, mRNA processing and in stabilization of genomic DNA structure. To our knowledge, this is the first experimental evidence that muscle FBPase is involved in cell cycle events. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is a multifactorial disease with a heterogeneous tumor group that hampers diagnostic and therapeutic approaches, as well as understanding of the processes that underlie its pathogenesis. Current research efforts are focused on examining alterations in the tumor microenvironment, which may affect the pathogenesis and further malignant progression in lung cancer. The aim of this study was to investigate changes in the levels of biomarkers involved in the lung tumor microenvironment and their diagnostic utility in differentiating lung cancer subtypes and stages. Methods: This study comprised 112 lung cancer patients, 50 with adenocarcinoma, 35 with squamous cell carcinoma, 13 with other non-small cell lung carcinoma subtypes, and 14 with other lung neoplasms than non-small cell lung carcinoma. Tumor markers (CEA, CYFRA 21-1, and NSE) were measured in the patients' sera and plasmas, along with IL-6, TNF-α, SAA1, CRP, MMP-2, MMP-9, glucose, lactate, and LDH, utilizing enzyme-linked immunosorbent assays, enzyme immunoassays, and automated clinical chemistry and turbidimetry systems. The results were statistically analyzed across patient groups based on the subtype and stage of lung cancer. Results: Glucose concentrations showed statistically significant (p < 0.05) differences both between lung cancer subtypes and stages, with the highest levels in patients with other lung neoplasms (me = 130.5 mg/dL) and in patients with stage IIB lung cancer (me = 132.0 mg/dL). In patients with advanced lung cancer, IL-6 and LDH had considerably higher concentration and activity. There was also a significant positive correlation between IL-6 and MMP-9 in adenocarcinoma and SqCC, with correlation coefficients of 0.53 and 0.49, respectively. The ROC analyses showed that the best single biomarkers for distinguishing adenocarcinoma from squamous cell carcinoma are glucose, CRP, and CYFRA 21-1; however, their combination did not significantly improve sensitivity, specificity, and the AUC value. The combinations of IL-6, glucose, LDH and CEA, IL-6, SAA1, MMP-9, and lactate can distinguish patients with stage IIB lung cancer from those with stage IIA with 100% sensitivity, 100% specificity, and with an AUC value of 0.8333 and 1.0000, respectively, whereas the combination of CEA, IL-6, and LDH can identify patients with stage IIIA lung cancer from those with stage IIB with 72.73% sensitivity, 94.44% specificity, and an AUC value of 0.8686. Conclusion: There is a link between biomarkers of tumor microenvironment changes and tumor markers, and combinations of these markers may be clinically useful in the differential diagnosis of adenocarcinoma and squamous cell carcinoma, as well as lung cancer stages IIB and IIA, and IIIA and IIB. [ABSTRACT FROM AUTHOR]

Primary cell cultures are challenging, but reliable model reflecting tumor response in vitro. The study was designed to examine if the increased electropermeabilization can overcame initial drug insensitivity in chondrosarcoma cells from lung metastasis. We established a primary cell culture and evaluated the cytotoxic impact of four drugs—cisplatin (CDDP), camptothecin, 2‐methoxyestradiol, and leucovorin calcium (LeuCa). After determination of parameters allowing for electropermeabilization, we performed electrochemotherapy in vitro with the least toxic drugs—CDDP and LeuCa. Although combining CDDP and leucovorin together increased their toxicity and supported apoptosis, application of pulsed electric fields (PEFs) brought no advantage for their efficacy. The study emphasizes the need for introduction of primary cell cultures into studies on pulse electric fields as model frequently less sensitive to PEF‐based treatments than continuous cell lines. [ABSTRACT FROM AUTHOR]

Despite the rapid progression of cancer pharmacotherapy, the high drug resistance of pancreatic ductal adenocarcinoma (PDA) makes it one of the most lethal malignancies. Therefore, there are high expectations associated with experimental therapies, such as electrochemotherapy (ECT). This technique involves the application of short electric pulses to induce transitional permeabilization of the cellular membrane, thus enhancing drug molecules influx. The aim of the study was to investigate the influence of electroporation with cisplatin (CisEP) on the primary culture of human PDA cells from lung metastases—their survival and stress response. Considering the growing importance of various research models, two established human PDA cell lines, EPP85-181P (sensitive to daunorubicin) and EPP85-181RDB (resistant to daunorubicin), were utilized as a reference control. Cisplatin revealed higher cytotoxicity towards established cell lines. Following CisEP application, we observed a significant decrease of cells viability in the primary culture model. After CisEP therapy, an increased immunoreactivity with SOD-2 and Casp-3 antibodies was noticed. In conclusion, we discovered that electroporation can enhance the cytotoxic effect of cisplatin in pancreatic cancer cells in vitro. This effect was evident for cells from the primary culture. The obtained results confirm the importance of primary cells models in studies on the efficacy of experimental cancer therapies. [ABSTRACT FROM AUTHOR]

Pulsed electric fields (PEFs) are commonly used to facilitate the delivery of various molecules, including pharmaceuticals, into living cells. However, the applied protocols still require optimization regarding the conditions of the permeabilization process, i.e., pulse waveform, voltage, duration, and the number of pulses in a burst. This study highlights the importance of electrochemical processes involved in the electropermeabilization process, known as electroporation. This research investigated the effects of electroporation on human non-small cell lung cancer cells (A549) in potassium (SKM) and HEPES-based buffers (SHM) using sub-microsecond and microsecond range pulses. The experiments were performed using 100 ns – 100 μs (0.6–15 kV/cm) bursts with 8 pulses in a sequence. It was shown that depending on the buffer composition, the susceptibility of cells to PEF varies, while calcium enhances the cytotoxic effects of PEF, if high cell membrane permeabilization is triggered. It was also determined that electroporation with calcium ions induces oxidative stress in cells, including lipid peroxidation (LPO), generation of reactive oxygen species (ROS), and neutral lipid droplets. Here, we demonstrated that calcium ions and optimized pulse parameters could potentiate PEF efficacy and oxidative alternations in lung cancer cells. Thus, the anticancer efficacy of PEF in lung cancers in combination with standard cytostatic drugs or calcium ions should be considered, but this issue still requires in-depth detailed studies with in vivo models. [Display omitted] • ns and μsPEF with calcium ions are efficient method against lung cancer cells. • Calcium electroporation efficacy is dependent on the external buffer conductivity. • Calcium electroporation stimulates ROS release and lipid peroxidation. • Calcium electroporation reduced lipid droplets content in lung cancer cells. [ABSTRACT FROM AUTHOR]

Computed tomography is performed in every patient before lung tumour resection. The presented case realises how important it is to perform this study with contrast. In a 75-yearold male we detected a tumour ingrowing from the right lung through the right lower pulmonary vein into the left atrium of the heart. The patient was qualified for primary sternotomy with extracorporeal circulation and resection of the intracardiac part of the tumour. In the second stage, right-sided thoracotomy was performed, and right lower lung lobectomy was done. Mixed heterogeneous lung cancer was diagnosed (squamous cell and non-small cell endocrine) in stage IIIa. The perioperative period was uncomplicated. The patient, due to renal failure, was not eligible for adjuvant chemotherapy. If the patient were qualified for lobectomy based directly on computed tomography without contrast, there would have been a high risk of perioperative death due to embolic incidents and heart failure. Effective multidisciplinary collaboration allowed us to avoid this sort of complication. [ABSTRACT FROM AUTHOR]

Aim of the study: The resection of pulmonary metastases is a routine practice of thoracic surgery wards; however, clear protocols or prognostic factors defining the surgical treatment criteria are still not available. The aim of the study is to evaluate the prognostic factors associated with long-term survival in a group of patients who underwent resection of pulmonary metastases. Material and methods: A retrospective analysis was conducted on a group of 250 patients admitted to the Wroclaw Thoracic Surgery Centre for radical resection of pulmonary lesions in the years 1996-2010. Results: The patients included in the study (n = 250) underwent 339 thoracotomies in total. The overall five-year survival was 52.8%. The univariate data analysis showed that the survival rate was significantly better in patients subjected to more than one thoracotomy (p = 0.01674). Among the other data, such as sex, tumour histology, disease-free interval (DFI) ≤ 12 and > 12 months, DFI ≤ 36 and > 36 months, age, number of tumours identified in CT and number of tumours subject to resection, operated side, resection type, radicality of resection, extent of lymphadenectomy, and adjuvant therapy, no statistical significance was observed in univariate and multivariate analysis (p > 0.05). Conclusions: Outcomes of re-metastasectomy are satisfactory if patients meet the baseline criteria for surgical treatment. None of the evaluated factors potentially influencing the patient survival was demonstrated to have any prognostic value. Further research, including the biology of tumours with pulmonary metastases, is necessary to select the group of patients that will benefit most from surgical treatment. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is the most commonly diagnosed cancer and the most frequent cause of cancer-associated mortality worldwide. Tesmin (MTL5) is a 60 kDa protein which has cysteine rich motifs, characteristic of metallothioneins. Tesmin expression was first observed in germ cells during spermatogenesis. Increased tesmin expression in NSCLC has been described previously. Minichromosome maintenance proteins (MCMs) serve a critical role in replication and cell cycle progression, i.e. in NSCLC. The aim of the present study was to evaluate the localization and intensity of tesmin, MCM5 and MCM7 protein expression in NSCLC and their association with the clinicopathological data of patients. Archival paraffin blocks of 243 cases of NSCLC and 104 non-cancerous tissue samples from the surgical margin (control) were obtained from patients treated at the Clinic of Thoracic Surgery of Wroclaw Medical University (Wroclaw, Poland) between 2010 and 2016, and were used for tissue microarrays and immunohistochemical (IHC) experiments. Laser capture microdissection was used for the isolation of cancer cells from 36 frozen samples of NSCLC and 8 control samples, and subsequently, MTL5, MCM5 and MCM7 mRNA expression was detected separately by reverse transcription-quantitative PCR. Positive cytoplasmic and nuclear tesmin, as well as nuclear MCM5 and MCM7 IHC expression were observed in 95.1, 83.67, 95.51 and 100% of the NSCLC cases, respectively. MTL5, MCM5 and MCM7 mRNA expression was observed in 91.66% of the cancer cases for all genes. The statistical analysis revealed increased tesmin IHC expression in cancer cells compared with the control. A positive correlation was observed between the IHC expression of nuclear tesmin and MCM5 proteins (r=0.33; P<0.0001) and nuclear tesmin and MCM7 proteins (r=0.315; P<0.0001). In addition, a positive correlation between the mRNA expression levels of MTL5 and MCM5 (r=0.421; P<0.05), MTL5 and MCM7 (r=0.557; P<0.01) was demonstrated. The survival analysis revealed that the presence of IHC cytoplasmic tesmin expression was a positive prognostic marker in NSCLC (P=0.0524). Furthermore, in vitro experiments performed on the NCI-H1703 cell line revealed that silencing of MTL5 mRNA and tesmin caused the downregulation of the expression levels of MCM5 and MCM7 and decreased the number of cells in the G2 phase. A positive association among tesmin, MCM5 and MCM7 could indicate a possible role of tesmin in the proliferation of NSCLC cancer cells. [ABSTRACT FROM AUTHOR]