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Abstract Epithelial ovarian cancer (EOC) is one of the leading cancers in women, with high-grade serous ovarian cancer (HGSOC) being the most common and lethal subtype of this disease. A vast majority of HGSOC are diagnosed at the late stage of the disease when the treatment and total recovery chances are low. Thus, there is an urgent need for novel, more sensitive and specific methods for early and routine HGSOC clinical diagnosis. In this study, we performed miRNA expression profiling using the NanoString miRNA assay in 34 serum samples from patients with HGSOC and 36 healthy women. We identified 13 miRNAs that were differentially expressed (DE). For additional exploration of expression patterns correlated with HGSOC, we performed weighted gene co-expression network analysis (WGCNA). As a result, we showed that the module most correlated with tumour size, nodule and metastasis contained 8 DE miRNAs. The panel including miR-1246 and miR-150-5p was identified as a signature that could discriminate HGSOC patients with AUCs of 0.98 and 1 for the training and test sets, respectively. Furthermore, the above two-miRNA panel had an AUC = 0.946 in the verification cohorts of RT-qPCR data and an AUC = 0.895 using external data from the GEO public database. Thus, the model we developed has the potential to markedly improve the diagnosis of ovarian cancer.

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.

Abstract Metabolomics combined with machine learning methods (MLMs), is a powerful tool for searching novel diagnostic panels. This study was intended to use targeted plasma metabolomics and advanced MLMs to develop strategies for diagnosing brain tumors. Measurement of 188 metabolites was performed on plasma samples collected from 95 patients with gliomas (grade I–IV), 70 with meningioma, and 71 healthy individuals as a control group. Four predictive models to diagnose glioma were prepared using 10 MLMs and a conventional approach. Based on the cross-validation results of the created models, the F1-scores were calculated, then obtained values were compared. Subsequently, the best algorithm was applied to perform five comparisons involving gliomas, meningiomas, and controls. The best results were obtained using the newly developed hybrid evolutionary heterogeneous decision tree (EvoHDTree) algorithm, which was validated using Leave-One-Out Cross-Validation, resulting in an F1-score for all comparisons in the range of 0.476–0.948 and the area under the ROC curves ranging from 0.660 to 0.873. Brain tumor diagnostic panels were constructed with unique metabolites, which reduces the likelihood of misdiagnosis. This study proposes a novel interdisciplinary method for brain tumor diagnosis based on metabolomics and EvoHDTree, exhibiting significant predictive coefficients.

According to the fifth edition of the WHO Classification of Tumours of the Central Nervous System (CNS) published in 2021, grade 4 gliomas classification includes IDH-mutant astrocytomas and wild-type IDH glioblastomas. Unfortunately, despite precision oncology development, the prognosis for patients with grade 4 glioma remains poor, indicating an urgent need for better diagnostic and therapeutic strategies. Circulating miRNAs besides being important regulators of cancer development could serve as promising diagnostic biomarkers for patients with grade 4 glioma. Here, we propose a two-miRNA miR-362-3p and miR-6721-5p screening signature for serum for non-invasive classification of identified glioma cases into the highest-grade 4 and lower-grade gliomas. A total of 102 samples were included in this study, comprising 78 grade 4 glioma cases and 24 grade 2–3 glioma subjects. Using the NanoString platform, seven miRNAs were identified as differentially expressed (DE), which was subsequently confirmed via RT-qPCR analysis. Next, numerous combinations of DE miRNAs were employed to develop classification models. The dual panel of miR-362-3p and miR-6721-5p displayed the highest diagnostic value to differentiate grade 4 patients and lower grade cases with an AUC of 0.867. Additionally, this signature also had a high AUC = 0.854 in the verification cohorts by RT-qPCR and an AUC = 0.842 using external data from the GEO public database. The functional annotation analyses of predicted DE miRNA target genes showed their primary involvement in the STAT3 and HIF-1 signalling pathways and the signalling pathway of pluripotency of stem cells and glioblastoma-related pathways. For additional exploration of miRNA expression patterns correlated with glioma, we performed the Weighted Gene-Co Expression Network Analysis (WGCNA). We showed that the modules most associated with glioma grade contained as many as six DE miRNAs. In conclusion, this study presents the first evidence of serum miRNA expression profiling in adult-type diffuse glioma using a classification based on the WHO 2021 guidelines. We expect that the discovered dual miR-362-3p and miR-6721-5p signatures have the potential to be utilised for grading gliomas in clinical applications.

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.

Mesenchymal stem cells (mesenchymal stromal cells; MSC)-based therapies remain a promising approach to treat degenerative and inflammatory diseases. Their beneficial effects were confirmed in numerous experimental models and clinical trials. However, safety issues concerning MSCs’ stability and their long-term effects limit their implementation in clinical practice, including treatment of respiratory diseases such as asthma, chronic obstructive pulmonary disease, and COVID-19. Here, we aimed to investigate the safety of intranasal application of human adipose tissue-derived MSCs in a preclinical experimental mice model and elucidate their effects on the lungs. We assessed short-term (two days) and long-term (nine days) effects of MSCs administration on lung morphology, immune responses, epithelial barrier function, and transcriptomic profiles. We observed an increased frequency of IFNγ- producing T cells and a decrease in occludin and claudin 3 as a long-term effect of MSCs administration. We also found changes in the lung transcriptomic profiles, reflecting redox imbalance and hypoxia signaling pathway. Additionally, we found dysregulation in genes clustered in pattern recognition receptors, macrophage activation, oxidative stress, and phagocytosis. Our results suggest that i.n. MSCs administration to noninflamed healthy lungs induces, in the late stages, low-grade inflammatory responses aiming at the clearance of MSCs graft.

The diagnosis of brain gliomas is mainly based on imaging methods. The gold standard in this area is MRI. Recommendations for the prevention, diagnosis, and treatment of gliomas are periodically modified and updated. One of the diagnostic techniques used when a brain glioma is suspected is liquid biopsy. However, this technique requires further development to confirm its effectiveness. This paper presents a proposal of three potential biomarkers of brain gliomas—extracellular matrix metalloproteinase-1 (MMP-1), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and the 20S proteasome—which were quantified in blood plasma using SPRi biosensors. A statistical analysis of the results indicated no significant changes in the concentrations between the control group (K) and grades G1 and G2, and similarly between grades G3 and G4. However, the differences in the concentrations between the groups K/G1/G2 and G3/G4 were statistically significant. A positive average correlation was found between the concentrations of the proteins and the patient’s age. The individual tested proteins were also highly correlated with each other. Our work proposes a new diagnostic technique that may aid in the diagnosis of brain gliomas.

The presented work is based on the quantification of LN-5, FN, and COL IV in blood plasma as potential biomarkers in patients diagnosed with glioma in grades G1 to G4. The obtained concentration results were compared with the protein content in the control group, which consisted of smokers of different ages. The obtained results were statistically analysed and interpreted based on the available clinical description. Quantitative determinations of LN-5, FN, and COL IV were performed with the use of SPRi biosensors specific to the tested proteins. Comparing groups K and G4, as well as G2 and G4, statistically significant relationships between changes in the concentration of individual proteins, were observed. The analysis showed significant correlations between FN and LN-5, between FN and COL IV, and between LN-5 and COL IV. There was a moderate positive correlation between individual proteins and the age of the patient. The ROC analysis distinguished patients with advanced disease from the control group. The results of the research show that LN-5, FN, and COL IV are effective biomarkers of brain glioma that may be helpful in non-invasive diagnosis and determining the grade of the disease.

The evolution and genetic nature of metastatic lesions is not completely characterized. Here the authors perform a comprehensive whole-genome study of colorectal metastases in comparison to matched primary tumors and define a multistage progression model and metastasis-specific changes that, in part, are therapeutically actionable.

The management of hard-to-heal wounds is a significant clinical challenge. Acellular dermal matrices (ADMs) have been successfully introduced to enhance the healing process. Here, we aimed to develop protocol for the preparation of novel ADMs from abdominoplasty skin. We used three different decellularization protocols for skin processing, namely, 1M NaCl and sodium dodecyl sulfate (SDS, in ADM1); 2M NaCl and sodium dodecyl sulfate (SDS, in ADM1); and a combination of recombinant trypsin and Triton X-100 (in hADM 3). We assessed the effectiveness of decellularization and ADM’s structure by using histochemical and immunochemical staining. In addition, we evaluated the therapeutic potential of novel ADMs in a murine model of wound healing. Furthermore, targeted transcriptomic profiling of genes associated with wound healing was performed. First, we found that all three proposed methods of decellularization effectively removed cellular components from abdominoplasty skin. We showed, however, significant differences in the presence of class I human leukocyte antigen (HLA class I ABC), Talin 1/2, and chondroitin sulfate proteoglycan (NG2). In addition, we found that protocols, when utilized differentially, influenced the preservation of types I, III, IV, and VII collagens. Finally, we showed that abdominoplasty skin-derived ADMs might serve as an effective and safe option for deep wound treatment. More importantly, our novel dressing (ADM1) improves the kinetics of wound closure and scar maturation in the proliferative and remodeling phases of wound healing. In conclusion, we developed a protocol for abdominoplasty skin decellularization suitable for the preparation of biological dressings. We showed that different decellularization methods affect the purity, structure, and therapeutic properties of ADMs.

Chronic ulcerative and hard-healing wounds are a growing global concern. Skin substitutes, including acellular dermal matrices (ADMs), have shown beneficial effects in healing processes. Presently, the vast majority of currently available ADMs are processed from xenobiotic or cadaveric skin. Here we propose a novel strategy for ADM preparation from human abdominoplasty-derived skin. Skin was processed using three different methods of decellularization involving the use of ionic detergent (sodium dodecyl sulfate; SDS, in hADM 1), non-ionic detergent (Triton X-100 in hADM 2), and a combination of recombinant trypsin and Triton X-100 (in hADM 3). We next evaluated the immunogenicity and immunomodulatory properties of this novel hADM by using an in vitro model of peripheral blood mononuclear cell culture, flow cytometry, and cytokine assays. We found that similarly sourced but differentially processed hADMs possess distinct immunogenicity. hADM 1 showed no immunogenic effects as evidenced by low T cell proliferation and no significant change in cytokine profile. In contrast, hADMs 2 and 3 showed relatively higher immunogenicity. Moreover, our novel hADMs exerted no effect on T cell composition after three-day of coincubation. However, we observed significant changes in the composition of monocytes, indicating their maturation toward a phenotype possessing anti-inflammatory and pro-angiogenic properties. Taken together, we showed here that abdominoplasty skin is suitable for hADM manufacturing. More importantly, the use of SDS-based protocols for the purposes of dermal matrix decellularization allows for the preparation of non-immunogenic scaffolds with high therapeutic potential. Despite these encouraging results, further studies are needed to evaluate the beneficial effects of our hADM 1 on deep and hard-healing wounds.

Advances in molecular analyses based on high-throughput technologies can contribute to a more accurate classification of non–small cell lung cancer (NSCLC), as well as a better prediction of both the disease course and the efficacy of targeted therapies. Here we set out to analyze whether global gene expression profiling performed in a group of early-stage NSCLC patients can contribute to classifying tumor subtypes and predicting the disease prognosis. Gene expression profiling was performed with the use of the microarray technology in a training set of 108 NSCLC samples. Subsequently, the recorded findings were validated further in an independent cohort of 44 samples. We demonstrated that the specific gene patterns differed significantly between lung adenocarcinoma (AC) and squamous cell lung carcinoma (SCC) samples. Furthermore, we developed and validated a novel 53-gene signature distinguishing SCC from AC with 93% accuracy. Evaluation of the classifier performance in the validation set showed that our predictor classified the AC patients with 100% sensitivity and 88% specificity. We revealed that gene expression patterns observed in the early stages of NSCLC may help elucidate the histological distinctions of tumors through identification of different gene-mediated biological processes involved in the pathogenesis of histologically distinct tumors. However, we showed here that the gene expression profiles did not provide additional value in predicting the progression status of the early-stage NSCLC. Nevertheless, the gene expression signature analysis enabled us to perform a reliable subclassification of NSCLC tumors, and it can therefore become a useful diagnostic tool for a more accurate selection of patients for targeted therapies.

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.

Purpose. Recently, it has been emphasized that hepatic progenitor/oval cells (HPCs) are significantly involved in liver fibrogenesis. We evaluated the multipotential population of HPCs by transmission electron microscope (TEM), including relations with adherent hepatic nonparenchymal cells (NPCs) in rats with biliary fibrosis induced by bile duct ligation (BDL). Methods. The study used 6-week-old Wistar Crl: WI(Han) rats after BDL for 1, 6, and 8 weeks. Results. Current ultrastructural analysis showed considerable proliferation of HPCs in experimental intensive biliary fibrosis. HPCs formed proliferating bile ductules and were scattered in periportal connective tissue. We distinguished 4 main types of HPCs: 0, I, II (bile duct-like cells; most common), and III (hepatocyte-like cells). We observed, very seldom presented in literature, cellular interactions between HPCs and adjacent NPCs, especially commonly found transitional hepatic stellate cells (T-HSCs) and Kupffer cells/macrophages. We showed the phenomenon of penetration of the basement membrane of proliferating bile ductules by cytoplasmic processes sent by T-HSCs and the formation of direct cell-cell contact with ductular epithelial cells related to HPCs. Conclusions. HPC proliferation induced by BDL evidently promotes portal fibrogenesis. Better understanding of the complex cellular interactions between HPCs and adjacent NPCs, especially T-HSCs, may help develop antifibrotic therapies in the future.

Littoral cell angioma (LCA) is a rare primary splenic vascular tumor, originating from the littoral cellslining the red pulp sinuses of the spleen. There are only a handful of case reports of LCA in children to be foundin the literature. We performed a retrospective analysis of the medical charts of pediatric patients with spleniclesions who were treated between 2005 and 2010 in the Pediatric Surgery Department of the Medical Universityof Bialystok. Surprisingly, LCA accounted for 37.5% of the splenic lesions found in our series. The majority ofLCA tumors are benign, but given their malignant potential, splenectomy and long-term follow-up should bethe gold standard for their management. We strongly support the use of further cross-sectional studies to properlyelucidate the prevalence of littoral cell angioma of the spleen in the pediatric population.Littoral cell angioma (LCA) is a rare primary splenic vascular tumor, originating from the littoral cellslining the red pulp sinuses of the spleen. There are only a handful of case reports of LCA in children to be foundin the literature. We performed a retrospective analysis of the medical charts of pediatric patients with spleniclesions who were treated between 2005 and 2010 in the Pediatric Surgery Department of the Medical Universityof Bialystok. Surprisingly, LCA accounted for 37.5% of the splenic lesions found in our series. The majority ofLCA tumors are benign, but given their malignant potential, splenectomy and long-term follow-up should bethe gold standard for their management. We strongly support the use of further cross-sectional studies to properlyelucidate the prevalence of littoral cell angioma of the spleen in the pediatric population.

Purpose. To evaluate the relationship between the expression of orbital tissue mRNA for FOXP3, CTLA-4/CD28/CD80/CD86, and CD40/CD40 and the severity of Graves’ orbitopathy (GO). Material and Methods. Orbital tissue was obtained from 26 patients with GO, with mild (n=6) or severe GO (n=20), and 7 healthy controls. The expression of mRNA of FOXP3, CTLA-4/CD28/CD80/CD86, CD40/CD40L was measured by RT-PCR. TCR and CD3 were evaluated by immunohistochemistry. Results. Higher mRNA for FoxP3 (relative expression: 1.4) and CD40 (1.27) and lower expression of CTLA-4 (0.61) were found in the GO tissues versus controls. In severe GO as compared to mild GO higher mRNA expression for FoxP3 (1.35) and CD40 (1.4) and lower expression for CTLA-4 (0.78), CD28 (0.62), and CD40L (0.56) were found. A positive correlation was found between FOXP3 mRNA and CD3 infiltration (R=0.796, P=0.0000001). Conclusions. The enhanced FOXP3 mRNA expression in GO samples may suggest the dysfunction of FOXP3 cells in the severe GO. The diminished mRNA expression of CTLA-4 in severe GO may indicate inadequate T regulatory function. The enhanced mRNA expression of CD40 in severe GO and negative correlation to CRP mRNA may suggest their role in the active and inactive GO.

Purpose. To assess FGF-β, TGF-β, and COX2 expression and immunocompetent cells in the orbital tissue of patients with severe and mild Graves’ orbitopathy. Patients and Methods. Orbital tissue was taken from 27 patients with GO: (1) severe GO (n=18), the mean clinical activity score (CAS) being 8.5 (SD 2.5); and (2) mild GO (n=9), the mean CAS being 2.2 (SD 0.8), and from 10 individuals undergoing blepharoplasty. The expression of CD4+, CD8+, CD20+, and CD68 and FGF-β, TGF-β, and COX2 in the orbital tissue was evaluated by immunohistochemical methods. Results. We demonstrated predominant CD4+ T cells in severe GO. CD68 expression was observed in the fibrous connective area of mild GO and was robust in severe GO, while the prominent TGF-β expression was seen in all GO. Increased FGF-β expression was observed in the fibroblasts and adipocytes of severe GO. No expression of COX2 was found in patients with GO. Conclusions. Macrophages and CD4 T lymphocytes are both engaged in the active/severe and long stage of inflammation in the orbital tissue. FGF-β and TGF-β expression may contribute to tissue remodeling, fibrosis, and perpetuation of inflammation in the orbital tissue of GO especially in severe GO.

Ferritin is found in all cells of the body, serving as a reservoir of iron and protecting against damage to the molecules that make up cellular structures. It has emerged as a biomarker not only for iron-related disorders but also for inflammatory diseases and conditions in which inflammation plays a key role, including cancer, neurodegeneration, and infection. Oxidative stress, which can cause cellular damage, is induced by reactive oxygen species generated during the Fenton reaction, activating signaling pathways associated with tumor growth and proliferation. This review primarily emphasizes basic studies on the identification and function of ferritin, its essential role in iron metabolism, its involvement in inflammatory diseases, and its potential as an important prognostic factor and biomarker for cancer detection.

AbstractIntroduction Taking into account the possibility of myelin-associated proteins having a role in brain tumour development, the study aimed to evaluate the diagnostic usefulness of myelin-associated proteins (Nogo-A, MAG, OMgp) released into extracellular space in patients with brain tumours.Patients and methods Protein concentration in primary brain tumour (n = 49) and non-tumoural subjects (n = 24) was measured in cerebrospinal fluid (CSF) and serum by means of ELISA. Immunohistochemistry for IDH1-R132H was done on 5-μm thick formalin-fixed, paraffin-embedded tumour sections with the use of an antibody specific for the mutant IDH1-R132H protein.Results The receiver operator characteristic curve analysis showed that CSF Nogo-A and serum MAG were useful in differentiating patients with primary brain tumour from non-tumoural individuals. This was also true in the case of the separate analysis of the astrocytic tumour versus non-tumoural groups and the meningeal tumour versus non-tumoural groups. Neither Nogo-A nor MAG or OMgp concentrations were significantly different, in serum or CSF, between IDH1 wild-type astrocytic brain tumour patients compared to IDH1 mutant patients.Conclusions Our results indicated the potential usefulness of CSF Nogo-A and serum MAG evaluation as circulating biomarkers of primary brain tumours. Because blood is relatively easy to obtain, future research should be conducted to explicitly indicate the value of serum MAG concentration evaluation as a brain tumour biomarker.Key messagesMyelin-associated proteins may be circulating brain tumour biomarkers.Nogo-A and MAG proteins seem to be the most useful in brain tumour diagnosis.Decreased CSF Nogo-A concentration is an adverse prognostic factor for patients’ survival.

Introduction Recent studies have revealed the presence of zinc and the expression of zinc transporter (ZnT) family members in most endocrine cell types. It was demonstrated that ZnT family plays an important role in the synthesis and secretion of many hormones. Moreover, recently ZnT8 was described as a newly islet autoantigen in type 1 diabetes. Materials and methods We studied the expression of ZnT8 transporter in thyroid tissues from patients with immune and non-immune thyroid diseases. The study was performed in thyroid tissues after thyroidectomy from patients with thyroid non-toxic nodular goitre (NTNG; n = 17, mean age 15.8 ± 2.2 years) and cases with Graves’ disease (n = 20, mean age 15.6 ± 2.8). In our study we investigated the expression of ZnT8 in human thyroid tissues from patients with immune and non-immune thyroid diseases using immunohistochemistry, Western Blot as well as immunofluorescence analyses. To the best of our knowledge, this is the first investigation which identified ZnT8 protein expression in human thyroid tissues, moreover, confirmed by three different laboratory techniques. Results and ConclusionsExpression of ZnT8 transporter was identified by immunohistochemistry in the thyroid tissues from paediatric patients with Graves’ disease (on +++) and non-toxic nodular goitre (on ++). ZnT8 transporter expression was found both in thyroid follicular cells (within the cytoplasm and cytoplasmic membrane in follicular cells) and C cells (membrane-cytoplasmic reaction) in fluorescence. Predominant expression of ZnT8 in band 41 kDa in immune than in non-immune thyroid disorders may suggest potential role of ZnT8 as a new thyroid autoanitgen but it requires further study on a larger cohort.

Papillary thyroid gland carcinoma is the most common type of malignancy of the endocrine system. Metastases to the pituitary gland have been described as a complication of papillary thyroid cancer in few reported cases since 1965. We report the case of a 68-year-old female patient with a well-differentiated form of thyroid gland cancer. Despite it being the most common malignant cancer of the endocrine system, with its papillary form being one of the two most frequently diagnosed thyroid cancers, the case we present is extremely rare. Sudden cardiac arrest during ventricular fibrillation occurred during hospitalization. Autopsy of the patient revealed papillary carcinoma of the thyroid, follicular variant, with metastasis to the sella turcica, and concomitant sarcoidosis of heart, lung, and mediastinal and hilar lymph nodes. Not only does atypical metastasis make our patient’s case most remarkable, but also the postmortem diagnosis of sarcoidosis makes her case particularly unusual.

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.

Obesity is a new risk factor, to which more and more research is devoted, related to the development of cancer. Many studies of recent years have drawn attention to the role of adipose tissue as an important internal endocrine organ. In the adipose tissue proteins are produced, referred to by the common name as adipokines. In the case of obesity, the neoplasm cells are constantly stimulated by pro-inflammatory cytokines and adipokines, among which leptin dominates. The studies show that leptin can affect the cancer cells through numerous phenomena, e.g. inflammation, cell proliferation, suppression of apoptosis and angiogenesis. In this literature review we examined the role of leptin in the development of the individual cancers: breast cancer, colorectal cancer, prostate cancer, ovarian cancer, endometrial cancer and brain neoplasms: glioma and meningioma. However, leptin has very complicated mechanisms of action which require better understanding in certain types of cancer.

Abstract Background Despite the previously suggested role of Neudesin in tumorigenesis and its potential as a novel target for the treatment of cancers, its prognostic value has never been examined. Thus, the aim of the study was to evaluate Neudesin concentrations in primary brain tumor patients and make a comparison with non-tumoral individuals. Methods Cerebrospinal fluid (CSF) and serum Neudesin concentration was evaluated by means of the ELISA method. Results The total group of brain tumor patients had statistically lower serum Neudesin concentrations compared to the non-tumoral group (P = 0.037). The meningeal tumor subgroup also had statistically lower serum Neudesin concentrations compared to the non-tumoral group (P = 0.012). The Astrocytic brain tumor subgroup had significantly higher CSF Neudesin concentrations compared to the non-tumoral group (P = 0.046). Neudesin Quotient (CSF concentration divided by serum concentration) in the astrocytic brain tumor subgroup was statistically higher compared to the non-tumoral group (P = 0.023). Males had statistically lower concentrations of the serum Neudesin compared to females (P = 0.047). Univariate linear regression analysis revealed that for women the serum Neudesin concentration was 1.53 times higher than for men. In the model of multivariate linear regression analysis, predictor variables influencing serum Neudesin concentrations included CSF Neudesin concentration and the Neudesin Quotient, if other model parameters are fixed. The developed model explains 82% of the variance in serum Neudesin concentration. Both linear regression models, univariate and multivariate, pointed to fewer factors with a potential to influence the Neudesin Quotient compared to serum Neudesin concentration. Conclusions In astrocytic brain tumor patients Neudesin concentrations within the cerebrospinal fluid are higher compared with non-tumoral individuals. Serum Neudesin concentration strongly correlates with its CSF level. In primary brain tumor patients serum Neudesin concentration is clearly gender-dependent. Linear regression models pointed to fewer factors that may influence the Neudesin Quotient value, which suggests it is a better biomarker of astrocytic brain tumors than serum and CSF Neudesin concentrations alone.

Oral leukoplakia is a clinical term relating to various morphological lesions, including squamous cell hyperplasia, dysplasia and carcinoma. Leukoplakia morphologically manifested as hyperplasia with epithelial dysplasia is clinically treated as precancerous condition. Nevertheless, there is a lack of good markers indicating the transformation of premalignancies towards cancer. A better understanding of the mechanical environment within the tissues where tumors grow might be beneficial for the development of prevention, diagnostic, and treatment methods in cancer management. Atomic force microscopy (AFM) and immunohistology techniques were used to assess changes in the stiffness and morphology of oral mucosa and leukoplakia samples at different stages of their progression towards cancer. The Young's moduli of the tested leukoplakia samples were significantly higher than those of the surrounding mucus. Robust inhomogeneity of stiffness within leukoplakia samples, reflecting an increase in regeneration and collagen accumulation (increasing density) in the extracellular matrix (ECM), was observed. Within the histologically confirmed cancer samples, Young's moduli were significantly lower than those within the precancerous ones. Inhomogeneous stiffness within leukoplakia might act as “a mechanoagonist” that promotes oncogenesis. In contrast, cancer growth might require the reorganization of tissue structure to create a microenvironment with lower and homogenous stiffness. The immunohistology data collected here indicates that changes in tissue stiffness are achieved by increasing cell/ECM density. The recognition of new markers of premalignancy will aid in the development of new therapies and will expand the diagnostic methods.

Bisphenol A (BPA), one of the most common endocrine disrupting chemicals, is a carbon-based synthetic compound used in the production of water bottles, cans, food packaging, dental materials, medical equipment, thermal paper, toys and articles for children. Bisphenol A has been associated with serious health effects in humans. It elicits several disorders and plays a role in the pathogenesis of several tumors such as breast, ovarian, prostate and colorectal cancer. The aim of the research is to review the latest literature assessing participation of BPA in the process of neoplasia. There is not much research on this subject and the role of BPA in the carcinogenesis is still not understood. The present review summarizes the current knowledge of the role of BPA in carcinogenesis.

Papillomas and squamous cell carcinomas are the most common conjunctival and eyelid lesions. The etiology is still unclear and recently human papillomavirus infection and p53 gene mutation have been taken into consideration. The aim of our study was the evaluation of HPV DNApresence and p53 gene mutation in 45 benign and 38 malignant squamous lesions of the conjunctiva and eyelid. For HPV detection PCR-RFLP and immunohistochemical reaction were used; for p53 gene mutation PCR-SSCP was used. Only 8.8% papillomas, 9.1% squamous cell cancers and 3.7% basal cell cancers (using PCR-RFLP method) and 26.6% papillomas, 7.4% squamous cell cancers and 9.1% basal cell cancers (using immunohisto-chemical reaction) were HPV positive. p53 gene mutation was evaluated in 24.4% papillomas, 54.5% squamous cell cancers and 22.2% basal cell cancers; most commonly in 6 and 7 exon. Human papillomavirus infection, opposite to p53 gene mutation, is not a significant etiological factor of the benign and malignant conjunctival and eyelid lesions development. [ABSTRACT FROM AUTHOR]

IntroductionIn cancer treatment an attempt has been made to pharmacologically regulate the proteasome functions, thus the aim was to test whether 20S proteasome chymotrypsin-like (ChT-L) activity has a role in glial brain tumors. Furthermore, we analyzed the correlation between proteasome activity and IL-8, CCL2, NF-κB1 and NF-κB2 concentrations, which impact on brain tumors has already been indicated.MethodsPlasma 20S proteasome ChT-L activity was assayed using the fluorogenic peptide substrate Suc-Leu-Leu-Val-Tyr-AMC in the presence of SDS. IL-8, CCL2, NF-κB1 and NF-κB2 concentration was analyzed with the use of ELISA method. Immunohistochemistry for IDH1-R132H was done on 5-microns-thick formalin-fixed, paraffin-embedded tumor sections with the use of antibody specific for the mutant IDH1-R132H protein. Labelled streptavidin biotin kit was used as a detection system.ResultsBrain tumor patients had statistically higher 20S proteasome ChT-L activity (0.649 U/mg) compared to non-tumoral individuals (0.430 U/mg). IDH1 wild-type patients had statistically higher 20S proteasome ChT-L activity (1.025 U/mg) compared to IDH1 mutants (0.549 U/mg). 20S proteasome ChT-L activity in brain tumor patients who died as the consequence of a tumor (0.649) in the following 2 years was statistically higher compared to brain tumor patients who lived (0.430 U/mg). In brain tumor patients the 20S proteasome ChT-L activity positively correlated with IL-8 concentration.ConclusionsElevated 20S proteasome ChT-L activity was related to the increased risk of death in glial brain tumor patients. A positive correlation between 20S proteasome ChT-L activity and IL-8 concentration may indicate the molecular mechanisms regulating glial tumor biology. Thus research on proteasomes may be important and should be carried out to verify if this protein complexes may represent a potential therapeutic target to limit brain tumor invasion.

Myxomas are the most common non-invasive but life-threatening cardiac neoplasms due to obstruction of heart chambers and risk of embolism in a manner resembling thromboembolism as well. They can occasionally disseminate via their detached fragments into the bloodstream to seed and grow as secondary still benign tumors. In this study we evaluated morphological and clinical aspects of 14 ancient, degenerated left or right-sided cardiac atrial myxomas with expression of CD9 and CD63, which are found to contribute to platelet activation, aggregation and, as a result, intratumoral thrombosis or fragmentation. The appearance of tumors varied from sessile to polypoid revealing that a higher rate of endocardial thrombosis was associated with sessile compared to polypoid myxomas and left-sided tumors compared to right-sided ones in our study. In the general aspect of ancient calcifications, amorphous calcification with intra-tumor thrombosis was noted more frequently in sessile tumors, while well-formed osseous metaplasia was usually a feature of polypoid tumors. In our material osseous metaplasia did not coexist with massive thrombosis and was found in polypoid, pedunculated myxomas. Most importantly, CD9 overexpression was recorded in every studied myxoma and CD63 gave a weak reaction in myxoma cells.

Glaucoma is a result of increased intraocular pressure leading to damage to retinal ganglion cells andoptic nerve axons. The aim of this study was to evaluate HIF-1 expression in optic nerve axons and retinalganglion cells in 42 eyes enucleated because of complete glaucoma compared to eyes removed because of injury.The immunohistochemical reaction was done and specimens were examined under a light microscope. 57% ofcases presented HIF-1 expression in the optic nerve axons, and 52.3% in the retinal ganglion cells. 20 out of 42(47.6%) cases were HIF-1 positive both in the optic nerve axons and in the retinal ganglion cells, and the stainingwas evident mostly in the nuclear and perinuclear area. Our present results indicate that HIF-1 expression inhypoxic conditions in glaucoma might be a very crucial stage in damage to retinal ganglion cells and optic nerveaxons, and might be a successful target for the implementation of neuroprotective drugs.Glaucoma is a result of increased intraocular pressure leading to damage to retinal ganglion cells andoptic nerve axons. The aim of this study was to evaluate HIF-1 expression in optic nerve axons and retinalganglion cells in 42 eyes enucleated because of complete glaucoma compared to eyes removed because of injury.The immunohistochemical reaction was done and specimens were examined under a light microscope. 57% ofcases presented HIF-1 expression in the optic nerve axons, and 52.3% in the retinal ganglion cells. 20 out of 42(47.6%) cases were HIF-1 positive both in the optic nerve axons and in the retinal ganglion cells, and the stainingwas evident mostly in the nuclear and perinuclear area. Our present results indicate that HIF-1 expression inhypoxic conditions in glaucoma might be a very crucial stage in damage to retinal ganglion cells and optic nerveaxons, and might be a successful target for the implementation of neuroprotective drugs.