First insight about the ability of specific glycerophospholipids to discriminate non-small cell lung cancer subtypes.

Introduction: Discrimination between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) subtypes in non-small cell lung cancer (NSCLC) patients is a significant challenge in oncology. Lipidomics analysis provides a promising approach for this differentiation. Methods: In an accompanying paper, we explored oxPCs levels in a cohort of 200 NSCLC patients. In this research, we utilized liquid chromatography coupled with mass spectrometry (LC-MS) to analyze the lipidomics profile of matching tissue and plasma samples from 25 NSCLC patients, comprising 11 ADC and 14 SCC cases. This study builds upon our previous findings, which highlighted the elevation of oxidised phosphatidylcholines (oxPCs) in NSCLC patients. Results: We identified eight lipid biomarkers that effectively differentiate between ADC and SCC subtypes using an untargeted approach. Notably, we observed a significant increase in plasma LPA 20:4, LPA 18:1, and LPA 18:2 levels in the ADC group compared to the SCC group. Conversely, tumour PC 16:0/18:2, PC 16:0/4:0; CHO, and plasma PC 16:0/18:2; OH, PC 18:0/20:4; OH, PC 16:0/20:4; OOH levels were significantly higher in the ADC group. Discussion: Our study is the first to report that plasma LPA levels can distinguish between ADC and SCC patients in NSCLC, suggesting a potential role for LPAs in NSCLC subtyping. This finding warrants further investigation into the mechanisms underlying these differences and their clinical implications.

Diagnostics and treatment of ovarian cancer in the era of precision medicine - opportunities and challenges.

Due to predictions of increasing incidences and deaths from ovarian cancer, this neoplasm is a challenge for modern health care. The advent of NGS technology has made it possible to understand the molecular characteristics of many cancers, including ovarian cancer. The data obtained in research became the basis for the development of molecularly targeted therapies thus leading to the entry of NGS analysis into the diagnostic process of oncological patients. This review presents targeted therapies currently in preclinical or clinical trials, whose promising results offer hope for their use in clinical practice in the future. As more therapeutic options emerge, it will be necessary to modify molecular diagnostic regimens to select the best treatment for a given patient. New biomarkers are needed to predict the success of planned therapy. An important aspect of public health is molecular testing in women with a familial predisposition to ovarian cancer enabling patients to be included in prevention programs. NGS technology, despite its high throughput, poses many challenges, from the quality of the diagnostic material used for testing to the interpretation of results and classification of sequence variants. The article highlights the role of molecular testing in ongoing research and also its role in the diagnostic and therapeutic process in the era of personalized medicine. The spread of genetic testing in high-risk groups, the introduction of more targeted therapies and also the possibility of agnostic therapies could significantly improve the health situation for many women worldwide.

Applied Molecular-Based Quality Control of Biobanked Samples for Multi-Omics Approach.

Biobanks are vital for high-throughput translational research, but the rapid development of novel molecular techniques, especially in omics assays, poses challenges to traditional practices and recommendations. In our study, we used biospecimens from oncological patients in Polish clinics and collaborated with the Indivumed Group. For serum/plasma samples, we monitored hemolysis, controlled RNA extraction, assessed cDNA library quality and quantity, and verified NGS raw data. Tissue samples underwent pathologic evaluation to confirm histology and determine tumor content. Molecular quality control measures included evaluating the RNA integrity number, assessing cDNA library quality and quantity, and analyzing NGS raw data. Our study yielded the creation of distinct workflows for conducting preanalytical quality control of serum/plasma and fresh-frozen tissue samples. These workflows offer customization options to suit the capabilities of different biobanking entities. In order to ensure the appropriateness of biospecimens for advanced research applications, we introduced molecular-based quality control methods that align with the demands of high-throughput assays. The novelty of proposed workflows, rooted in innovative molecular techniques, lies in the integration of these QC methods into a comprehensive schema specifically designed for high-throughput research applications.

Molecular features as promising biomarkers in ovarian cancer.

Ovarian cancer (OC) is a global challenge for modern medicine, ranking 7th for incidence and the 8th most common cause of mortality from cancers in women. Ovarian cancer has a poor prognosis, characterized by high morbidity and mortality, with detection occurring more frequently in advanced stages. Further issues lie within the heterogeneous nature of this pathology, as well as in its ability to develop multidrug resistance. Therefore, there is a burgeoning need to introduce effective screening for the general population, especially in high-risk groups such as individuals with a family history of cancer. Achieving this would be greatly assisted by identifying new biomarkers in order to, in turn, develop targeted therapies for patients. Advances in molecular biology techniques that enable cancer genetic characterization offer hope for personalized medicine. This article reviews the current findings on the biology of OC at the molecular level. Such knowledge may prove to be crucial and constitute a starting point for the development of new options for the early detection, prevention and treatment of OC.

Exploration of oxidized phosphocholine profile in non-small-cell lung cancer.

Introduction: Lung cancer is one of the most frequently studied types of cancer and represents the most common and lethal neoplasm. Our previous research on non-small cell lung cancer (NSCLC) has revealed deep lipid profile reprogramming and redox status disruption in cancer patients. Lung cell membranes are rich in phospholipids that are susceptible to oxidation, leading to the formation of bioactive oxidized phosphatidylcholines (oxPCs). Persistent and elevated levels of oxPCs have been shown to induce chronic inflammation, leading to detrimental effects. However, recent reports suggest that certain oxPCs possess anti-inflammatory, pro-survival, and endothelial barrier-protective properties. Thus, we aimed to measure the levels of oxPCs in NSCLC patients and investigate their potential role in lung cancer. Methods: To explore the oxPCs profiles in lung cancer, we performed in-depth, multi-level metabolomic analyses of nearly 350 plasma and lung tissue samples from 200 patients with NSCLC, including adenocarcinoma (ADC) and squamous cell carcinoma (SCC), the two most prevalent NSCLC subtypes and COPD patients as a control group. First, we performed oxPC profiling of plasma samples. Second, we analyzed tumor and non-cancerous lung tissues collected during the surgical removal of NSCLC tumors. Because of tumor tissue heterogeneity, subsequent analyses covered the surrounding healthy tissue and peripheral and central tumors. To assess whether the observed phenotypic changes in the patients were associated with measured oxPC levels, metabolomics data were augmented with data from medical records. Results: We observed a predominance of long-chain oxPCs in plasma samples and of short-chain oxPCs in tissue samples from patients with NSCLC. The highest concentration of oxPCs was observed in the central tumor region. ADC patients showed higher levels of oxPCs compared to the control group, than patients with SCC. Conclusion: The detrimental effects associated with the accumulation of short-chain oxPCs suggest that these molecules may have greater therapeutic utility than diagnostic value, especially given that elevated oxPC levels are a hallmark of multiple types of cancer.

Expression of VEGF, EGF, and Their Receptors in Squamous Esophageal Mucosa, with Correlations to Histological Findings and Endoscopic Minimal Changes, in Patients with Different GERD Phenotypes.

BACKGROUND: Gastroesophageal reflux disease (GERD) may present as nonerosive reflux disease (NERD), erosive esophagitis (EE), or be complicated by Barrett's esophagus (BE). The explanation as to what determines the phenotype of GERD is awaited. Therefore, we assessed the correlation between the growth factors expression and endoscopic as histologic findings in GERD patients. METHODS: The squamous esophageal epithelium of 50 patients (20-NERD, 7-EE, 15-BE, 8 controls) was examined by: (1) magnification endoscopy with evaluation of minimal GERD changes such as: microerosions, white spots, palisade blood vessels visibility, and intrapapillary capillary loops (IPCLs) appearance, (2) histology, (3) immunohistochemistry with evaluation of the expression of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and their receptors (VEGFR and EGFR). RESULTS: The expression of VEGF, but not VEGFR, EGF, and EGFR, was significantly increased in EE patients compared to NERD patients and controls. VEGF levels correlated significantly with the presence of white spots, but not with other minimal endoscopic and histologic features. The EGFR expression correlated positively with basal cell hyperplasia and enlarged IPCLs. CONCLUSIONS: Our findings suggest a correlation between growth factors expression and findings in conventional endoscopy, formation of endoscopic minimal changes, and histologic lesions.

Application of two-dimensional difference gel electrophoresis to identify protein changes between center, margin, and adjacent non-tumor tissues obtained from non-small-cell lung cancer with adenocarcinoma or squamous cell carcinoma subtype.

Lung cancer is responsible for the most cancer-related mortality worldwide and the mechanism of its development is poorly understood. Proteomics has become a powerful tool offering vital knowledge related to cancer development. Using a two-dimensional difference gel electrophoresis (2D-DIGE) approach, we sought to compare tissue samples from non-small-cell lung cancer (NSCLC) patients taken from the tumor center and tumor margin. Two subtypes of NSCLC, adenocarcinoma (ADC) and squamous cell carcinoma (SCC) were compared. Data are available via ProteomeXchange with identifier PXD032736 and PXD032962 for ADC and SCC, respectively. For ADC proteins, 26 significant canonical pathways were identified, including Rho signaling pathways, a semaphorin neuronal repulsive signaling pathway, and epithelial adherens junction signaling. For SCC proteins, nine significant canonical pathways were identified, including hypoxia-inducible factor-1α signaling, thyroid hormone biosynthesis, and phagosome maturation. Proteins differentiating the tumor center and tumor margin were linked to cancer invasion and progression, including cell migration, adhesion and invasion, cytoskeletal structure, protein folding, anaerobic metabolism, tumor angiogenesis, EMC transition, epithelial adherens junctions, and inflammatory responses. In conclusion, we identified several proteins that are important for the better characterization of tumor development and molecular specificity of both lung cancer subtypes. We also identified proteins that may be important as biomarkers and/or targets for anticancer therapy.

What do we know about inflammatory myofibroblastic tumors? - A systematic review.

BACKGROUND: Inflammatory myofibroblastic tumors (IMTs) are rare intermediate-grade neoplasms that have a high recurrence rate after excision and exhibit low metastatic potential. These tumors contain proliferating neoplastic, fibroblastic and myofibroblastic cells, and are also characterized by chronic inflammatory infiltration by lymphocytes, plasma cells, eosinophils, and histiocytes. They belong to the group of inflammatory spindle cell lesions. Some reactive lesions, such as inflammatory pseudotumors, may appear to be IMTs, which makes their differential diagnosis extremely difficult. The aim of this article is to compile the recent information on IMTs to aid in their diagnosis and treatment. METHODS: We reviewed articles published between 2017 and 2021, which were selected from online medical databases. In addition, some earlier articles and latest scientific monographies were analyzed. RESULTS: The terminology used for inflammatory spindle cell lesions seems to be confusing. The terms "inflammatory myofibroblastic tumors" and "inflammatory pseudotumors" are interchangeably used by many scientists. However, a detailed analysis of the development of terminology suggests that the term "inflammatory myofibroblastic tumors" should be used to refer to a neoplastic lesion. CONCLUSIONS: IMTs are rare neoplasms, which have not been investigated in detail due to the difficulty in collecting a large number of cases. Thus, our knowledge about this disease remains unsatisfactory. Recently developed techniques such as next-generation sequencing and computer-aided histopathological diagnosis may be useful in understanding the etiopathology of IMTs, which will help in the selection of the most appropriate therapy for patients.

The Ability of Metabolomics to Discriminate Non-Small-Cell Lung Cancer Subtypes Depends on the Stage of the Disease and the Type of Material Studied.

Identification of the NSCLC subtype at an early stage is still quite sophisticated. Metabolomics analysis of tissue and plasma of NSCLC patients may indicate new, and yet unknown, metabolic pathways active in the NSCLC. Our research characterized the metabolomics profile of tissue and plasma of patients with early and advanced NSCLC stage. Samples were subjected to thorough metabolomics analyses using liquid chromatography-mass spectrometry (LC-MS) technique. Tissue and/or plasma samples from 137 NSCLC patients were analyzed. Based on the early stage tissue analysis, more than 200 metabolites differentiating adenocarcinoma (ADC) and squamous cell lung carcinoma (SCC) subtypes as well as normal tissue, were identified. Most of the identified metabolites were amino acids, fatty acids, carnitines, lysoglycerophospholipids, sphingomyelins, plasmalogens and glycerophospholipids. Moreover, metabolites related to N-acyl ethanolamine (NAE) biosynthesis, namely glycerophospho (N-acyl) ethanolamines (GP-NAE), which discriminated early-stage SCC from ADC, have also been identified. On the other hand, the analysis of plasma of chronic obstructive pulmonary disease (COPD) and NSCLC patients allowed exclusion of the metabolites related to the inflammatory state in lungs and the identification of compounds (lysoglycerophospholipids, glycerophospholipids and sphingomyelins) truly characteristic to cancer. Our results, among already known, showed novel, thus far not described, metabolites discriminating NSCLC subtypes, especially in the early stage of cancer. Moreover, the presented results also indicated the activity of new metabolic pathways in NSCLC. Further investigations on the role of NAE biosynthesis pathways in the early stage of NSCLC may reveal new prognostic and diagnostic targets.

The first SARS-CoV-2 genetic variants of concern (VOC) in Poland: The concept of a comprehensive approach to monitoring and surveillance of emerging variants.

PURPOSE: We analyzed the SARS-CoV-2 genome using our integrated genome analysis system and present the concept of a comprehensive approach to monitoring and surveillance of emerging variants. MATERIAL/METHODS: A total of 69 SARS-CoV-2 positive samples (with Ct value â€‹≤ â€‹28) were tested. Samples included in this study were selected from 7 areas of eastern Poland. All samples were sequenced on an Illumina MiSeq platform using a 300-cycle MiSeq Reagent Kit v2. BWA was used for reads mapping on the reference SARS-CoV-2 sequence. SAMTools were used for post-processing of reads to genome assembly. Pango lineage and Nexstrain were used to identify variants and amino acid mutations. Statistical analysis was performed with R 4.0.2. RESULTS: This study shows the first confirmed case of SARS-CoV-2 in Poland with the lineage B.1.351 (known as 501Y.V2 South African variant), as well as another 18 cases with epidemiologically relevant lineage B.1.1.7, known as British variant. Supplementary analysis of SARS-CoV-2 sequences deposited in GISAID shows that the share of a new variant can change rapidly within one month. In addition, we show a complete, integrated concept of a networked system for analyzing the variability of the SARS-CoV-2 genome, which, used in the present study, generated data and a variant report within 6 days. CONCLUSION: The analyzed viral genomes showed considerable variability with simultaneous clear distinction of local clusters of genomes showing high similarity. Implementing real-time monitoring of new SARS-CoV-2 variants in Poland is urgently needed, and our developed system is available to be implemented on a large scale.

Transnasal endoscopic skull base surgery in the COVID-19 era: Recommendations for increasing the safety of the method.

Transnasal endoscopic skull base surgery (eSBS) has been adopted in recent years, in great part to replace the extended procedures required by external approaches. Though sometimes perceived as "minimally invasive", eSBS still necessitates extensive manipulations within the nose/paranasal sinuses. Furthermore, exposure of susceptible cerebral structures to light and heat emanated by the telescope should be considered to comprehensively evaluate the safety of the method. While the number of studies specifically targeting eSBS safety still remains scarce, the problem has recently expanded with the SARS-CoV-2 pandemic, which also has implications for the safety of the surgical personnel. It must be stressed that eSBS may directly expose the surgeon to potentially high volumes of virus-contaminated aerosol. Thus, the anxiety of both the patient and the surgeon must be taken into account. Consequently, safety requirements must follow the highest standards. This paper summarizes current knowledge on SARS-CoV-2 biology and the peculiarities of human immunology in respect of the host-virus relationship, taking into account the latest information concerning the SARS-CoV-2 worrisome affinity for the nervous system. Based on this information, a workflow proposal is offered for consideration. This could be useful not only for the duration of the pandemic, but also during the unpredictable timeline involving our coexistence with the virus. Recommendations include technical modifications to the operating theatre, personal protective equipment, standards of testing for SARS-CoV-2 infection, prophylactic pretreatment with interferon, anti-IL6 treatment and, last but not least, psychological support for the patient.

Mass spectrometry based proteomics and metabolomics in personalized oncology.

Precision medicine (PM) means the customization of healthcare with decisions and practices adjusted to the individual patient. It includes personalized diagnostics, patients' sub-classification, individual treatment selection and the monitoring of its effectiveness. Currently, in oncology, PM is based on the molecular and cellular features of a tumor, its microenvironment and the patient's genetics and lifestyle. Surprisingly, the available targeted therapies were found effective only in a subset of patients. An in-depth understanding of tumor biology is crucial to improve their effectiveness and develop new therapeutic targets. Completion of genetic information with proteomics and metabolomics can give broader knowledge about tumor biology which consequently provides novel biomarkers and indicates new therapeutic targets. Recently, metabolomics and proteomics have extensively been applied in the field of oncology. In the context of PM, human studies, with the use of mass spectrometry (MS) which allows the detection of thousands of molecules in a large number of samples, are the most valuable. Such studies, focused on cancer biomarkers discovery or patients' stratification, are presented in this review. Moreover, the technical aspects of MS-based clinical proteomics and metabolomics are described.

Identification of protein changes in the blood plasma of lung cancer patients subjected to chemotherapy using a 2D-DIGE approach.

A comparative analysis of blood samples (depleted of albumin and IgG) obtained from lung cancer patients before chemotherapy versus after a second cycle of chemotherapy was performed using two-dimensional difference gel electrophoresis (2D-DIGE). The control group consisted of eight patients with non-cancerous lung diseases, and the experimental group consisted of four adenocarcinoma (ADC) and four squamous cell carcinoma (SCC) patients. Analyses of gels revealed significant changes in proteins and/or their proteoforms between control patients and lung cancer patients, both before and after a second cycle of chemotherapy. Most of these proteins were related to inflammation, including acute phase proteins (APPs) such as forms of haptoglobin and transferrin, complement component C3, and clusterin. The variable expression of APPs can potentially be used for profiling lung cancer. The greatest changes observed after chemotherapy were in transferrin and serotransferrin, which likely reflect disturbances in iron turnover after chemotherapy-induced anaemia. Significant changes in plasma proteins between ADC and SCC patients were also revealed, suggesting use of plasma vitronectin as a potential marker of SCC.

The added value of magnifying endoscopy in diagnosing patients with certain gastroesophageal reflux disease.

PURPOSE: In most cases gastroesophageal reflux disease proceeds without macroscopic erosions in the esophagus. We aimed to clarify if abnormalities detectable in magnifying endoscopy may offer additional diagnostic criteria for gastroesophageal reflux disease and to what histopathologic structures do they correspond. PATIENTS/METHODS: Esophageal mucosa above and below Z-line was evaluated under x115 magnification in 67 gastroesophageal reflux disease patients (11 with erosive reflux disease, 28 with Barrett's esophagus, 28 with nonerosive reflux disease) and in 12 patients without gastroesophageal reflux disease (negative control group). Features characteristic of gastroesophageal reflux disease were specified by comparing erosive reflux disease and Barrett's esophagus patients with negative control group. Afterwards the presence of identified features were evaluated in nonerosive reflux disease group. Interobserver agreement in the recognition of the proposed criteria was rated. Biopsies collected from the mucosa above Z-line were evaluated histologically after hematoxylin and eosin staining. RESULTS: Endoscopic lesions characteristic of gastroesophageal reflux disease were: microerosions, abnormal intrapapillary capillary loops, obscured palisade vessels, white points, big triangular indentations of Z-line and villous mucosa below Z-line. The presence of two or more of the above features indicated gastroesophageal reflux disease with 97% sensitivity and 75% specificity. Substantial interobserver agreement was achieved in evaluation of obscured palisade vessels, abnormal intrapapillary capillary loops and white points. Endoscopic lesions were correlated to histology. Lesions identified with magnifying endoscopy were helpful in discerning between negative control group and nonerosive reflux disease patients. CONCLUSIONS: Magnifying endoscopy reveals abnormalities that can be used as additional endoscopic diagnostic criteria of gastroesophageal reflux disease.

Significance of mutations in the region coding for NS3/4 protease in patients infected with HCV genotype 1b.

BACKGROUND: Fast hepatitis C virus (HCV) replication is one of the reasons for frequent changes in viral genome. OBJECTIVES: The objective of this study was to evaluate the frequency and type of mutation in NS3/4 protease in patients with HCV genotype 1b and to determine the effect of the mutation on viral load, fibrosis stage, alanine aminotransferase (ALT) activity, and alpha-fetoprotein (AFP) level. MATERIAL AND METHODS: The study included 46 treatment-naïve patients, infected with HCV genotype 1b. Mutations were analyzed after isolating HCV RNA, and then evaluating the compliance of the amino acid sequence, using 3500 Genetic Analyzer (Applied Biosystems, Foster City, USA). RNA fragment from nucleotide 1-181 encoding NS3/4 protease was subjected to analysis. RESULTS: Mutations were demonstrated in 65% of subjects. Changes in the protease region affecting resistance to treatment (T54, Q80, V158, M175, D186) were detected in 10.8% of patients. Substitution mutation at T72 was found most frequently - in 49.9% of cases. In 13% of patients, mutation at G86 was demonstrated, including G86P in 5 patients and G86S in 1 patient. In the group of patients with T72 mutation, viral load was significantly higher (1.3 × 106 IU/mL vs 1.0 × 105 IU/mL; p = 0.01), AFP level was higher and fibrosis level was lower (1.26 vs 2.17; p = 0.008) compared to the patients without the mutation. Cryoglobulinemia was observed in 74% of patients with mutation at position T72. CONCLUSIONS: Natural mutations of the region coding for NS3/4 protease are found frequently in patients infected with genotype 1b, but they may cause resistance to antiviral agents only in 11% of patients. Changes were most frequently found at position T72. Mutations at position T72 are correlated with the cryoglobulinemia occurrence. This is a substitution mutation, accompanied by a high viral load, high ALT activity and AFP level, which may point to a more unfavorable influence of such a modified virus, compared to wild-type virus, onto pathological processes in the liver.

Systematic biobanking, novel imaging techniques, and advanced molecular analysis for precise tumor diagnosis and therapy: The Polish MOBIT project.

Personalized and precision medicine is gaining recognition due to the limitations by standard diagnosis and treatment; many areas of medicine, from cancer to psychiatry, are moving towards tailored and individualized treatment for patients based on their clinical characteristics and genetic signatures as well as novel imaging techniques. Advances in whole genome sequencing have led to identification of genes involved in a variety of diseases. Moreover, biomarkers indicating severity of disease or susceptibility to treatment are increasingly being characterized. The continued identification of new genes and biomarkers specific to disease subtypes and individual patients is essential and inevitable for translation into personalized medicine, in estimating both, disease risk and response to therapy. Taking into consideration the mostly unsolved necessity of tailored therapy in oncology the innovative project MOBIT (molecular biomarkers for individualized therapy) was designed. The aims of the project are: (i) establishing integrative management of precise tumor diagnosis and therapy including systematic biobanking, novel imaging techniques, and advanced molecular analysis by collecting comprehensive tumor tissues, liquid biopsies (whole blood, serum, plasma), and urine specimens (supernatant; sediment) as well as (ii) developing personalized lung cancer diagnostics based on tumor heterogeneity and integrated genomics, transcriptomics, metabolomics, and radiomics PET/MRI analysis. It will consist of 5 work packages. In this paper the rationale of the Polish MOBIT project as well as its design is presented. (iii) The project is to draw interest in and to invite national and international, private and public, preclinical and clinical initiatives to establish individualized and precise procedures for integrating novel targeted therapies and advanced imaging techniques.

Development of LC-QTOF-MS method for human lung tissue fingerprinting. A preliminary application to nonsmall cell lung cancer.

The major histologic subtypes of non-small cell lung cancer (NSCLC) include adenocarcinoma (ADC), squamous cell lung carcinoma (SCC), and large-cell carcinoma (LCC). Clinical trials of targeted agents and newer chemotherapy agents yielded differences in outcomes according to histologic subgroups providing a rationale for histology-based treatment in NSCLC. Currently, NSCLC subtyping is performed based on histopathological examinations and immunohistochemistry. However available methods leave about 10% of NSCLC cases as not otherwise specified. The purpose of this study was development of an LC-QTOF-MS method for human lung tissue metabolic fingerprinting that could discriminate NSCLC histological subtypes and propose biomarkers candidates that could support proper NSCLC diagnosis. Metabolites were extracted with acetonitrile or methanol/ethanol and different chromatographic conditions were tested. In the final method 10 mg of lung tissue was homogenized with 50% methanol and metabolites were extracted with acetonitrile. Metabolites were separated on C8-RP and HILIC columns. About 3500 and 2000 of metabolic features (in both ion modes) were detected with good repeatability (CV < 20%) by RP and HILIC methods, respectively. Lung tumor and control tissue samples obtained from NSCLC patients were analyzed with developed methodology. Acylcarnitines, fatty acids, phospholipids, and amino acids were found more abundant in tumor as compared to control tissue. Acylcarnitines, lysophospholipids, creatinine, creatine, and alanine were identified as potential targets enabling classification of NSCLC subtypes.

Expression of CD117, DOG-1, and IGF-1R in gastrointestinal stromal tumours - an analysis of 70 cases from 2004 to 2010.

INTRODUCTION: Determination of the type of mutations in gastrointestinal stromal tumours (GIST) plays a major role in assessing the risk of progression of the disease, and also allows determination of the clinical management and treatment. More accurate GIST diagnosis is possible by using simultaneously various types of antibodies to immunohistochemistry methods in routine procedures. AIM: To evaluate the expression of CD117, DOG-1, and IGF-1R in patients with gastrointestinal stromal tumours, and analysis of the impact of the examined protein expression on patient survival with emphasis on specific recognition and prognostication of these tumours. MATERIAL AND METHODS: The protein expression was analyzed in 70 patients who had undergone surgical treatment for mesenchymal tumours of the gastrointestinal tract, using the immunohistochemical method. RESULTS: Positive expression of CD117, DOG-1, and IGF1R included 95.71%, 88.57% and 11.43% of study GISTs, respectively. Statistical analysis showed positive significant correlation between DOG-1 expression and histological type of tumour (p = 0.024). Analysis of overall survival curves of 70 GIST patients according to expression of CD117, DOG-1, and IGF1R did not show a tendency towards longer survival of patients with positive expression (p > 0.05). CONCLUSIONS: Predictive factors determining the survival time of patients are strongly associated with morphological features of tumours. A thorough analysis of each case plays a key role in predicting survival time of patients and may be a clue in targeting the therapeutic procedure.

Mesenteric lymphadenitis caused by Yersinia enterocolitica.

Yersiniosis is an acute or chronic, zoonotic disease caused by infection of Gram-negative rods Yersinia enterocolitica. It can be transmitted by the consumption of originally contaminated food products (pork, unpasteurized milk) or secondarily contaminated with animal or vegetable products. The clinical picture of infection may have a variable course is related to the age and physical condition of the patient, or pathogenic properties of microorganisms. Infection caused by Y. enterocolitica can occur in different clinical forms: food poisoning, colitis, mesentric lymphadenitis, erythema nodosum, arthritis, pharyngitis, pneumonia, meningitis, sepsis. The aim of this study was to present a rare case of infection with Y. enterocolitica mesenteric lymph nodes coexistent with appendicitis.

Increased MET Gene Copy Number but Not mRNA Level Predicts Postoperative Recurrence in Patients with Non-Small Cell Lung Cancer.

The aim of the present study was to investigate the relationship of MET copy number (CN) and MET mRNA expression to other molecular alterations, clinicopathologic characteristics, and survival of patients with resected non-small cell lung cancer. One hundred fifty-one paired surgical samples of tumor and tumor-distant normal lung tissues were analyzed by comparative quantitative polymerase chain reaction (PCR) methods with commercially available assays and the CopyCaller software v. 1.0 for post-PCR data processing (downloadable from www.appliedbiosystems.com). MET copy gain (set as more than 3.0 copies per cell) was found in 18.5% of the samples and occurred more frequently in the adenocarcinomas (ADCs) with an increased epidermal growth factor receptor (EGFR) or human epidermal growth factor receptor 2 (HER2) CN (P = .001 and .030 for EGFR and HER2, respectively) and in the ADCs with EGFR activating mutations (P = .051) but did not correlate with KRAS dosage or mutational status. MET mRNA level was 1.76-fold higher [95% confidence interval (CI), 1.29-2.40] in the tumor compared to unaffected lung tissue and associated significantly with MET CN (beta coefficient, 1.51; 95% CI, 1.22-1.87; P < .001). In the multivariable analysis, patients diagnosed with ADC with increased MET CN had a significantly higher risk of disease recurrence (hazard ratio, 1.76; 95% CI, 1.20-2.57; P = .004). An increased MET CN in combination with histologic type appears to be a prognostic factor in patients with ADC after a curative surgery.