Macrophage migration inhibitory factor (MIF) predicts survival in patients with clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of the most common subtypes of renal cancer, with 30% of patients presenting with systemic disease at diagnosis. This aggressiveness is a consequence of the activation of epithelial-mesenchymal transition (EMT) caused by many different inducers or regulators, signaling cascades, epigenetic regulation, and the tumor environment. Alterations in EMT-related genes and transcription factors are associated with poor prognosis in ccRCC. EMT-related factors suppress E-cadherin expression and are associated with tumor progression, local invasion, and metastasis. The aim of this study was to investigate the expression levels and prognostic significance of macrophage migration inhibitory factor (MIF), ß-catenin, and E-cadherin in ccRCC patients. We examined these proteins immunohistochemically in tumor areas and adjacent normal tissues resected from patients with ccRCC. Analysis of the cancer genome atlas (TCGA) cohort was performed to verify our results. Kaplan-Meier analysis showed that median overall survival (OS) was significantly shorter in patients with tumors exhibiting high MIFn and MIFm-c levels compared to those with low MIFn and MIFm-c levels (p = 0.03 and p = 0.007, respectively). In the TCGA cohort, there was a significant correlation between MIF expression and OS (p < 0.0001). In conclusion, this study provides further evidence for the biological and prognostic value of MIF in the context of EMT as a potential early prognostic marker for advanced-stage ccRCC.

Effect of Systemic Prednisone Treatment on Changes of Inflammation Markers in Chronic Rhinosinusitis.

(1) Objective: We aimed to evaluate the effect of treatment with prednisone on nasal and systemic periostin and eotaxin expression, IgE in plasma and eosinophils in tissue. (2) Methods: We compared the values of nasal and systemic periostin, eotaxin, IgE and eosinophils in tissue in patients treated with only nasal steroids before FESS, group 1, with those treated with an oral steroid-prednisone, group 2. (3) Results: A statistically significant decrease in the level of periostin, eotaxin and IgE in plasma was achieved in patients treated with prednisone one week before and after surgery (in sequence: p < 0.0476, p < 0.0006, p < 0.0031). In patients treated with steroids, we also observed a lower level of periostin in the epithelium (p < 0.044), eotaxin in the stroma (p limit value < 0.075) and eosinophils (p < 0.031) in the tissues collected during the operation. (4) Conclusions: Systemic steroid treatment with prednisone distinctly decreases periostin, eotaxin and IgE expression in plasma. We also observed a lower level of periostin in the epithelium, eotaxin in the stroma and eosinophils in the tissues. We need more attempts to find inflammatory markers associated with chronic rhinosinusitis. Identifying drugs that decrease inflammatory parameters would allow for more targeted therapy.

TOLLIP Protein Expression Predicts Unfavorable Outcome in Renal Cell Carcinoma.

Resistance to systemic therapy is one of the hallmarks of renal cell carcinoma (RCC). Recently, TOLLIP has emerged as a possible driver of autophagy and chemoresistance. We explored the relationship between primary and metastatic RCC tumor characteristics, patient survival, and TOLLIP expression. The tissue microarrays cohort contained 95 cores of the primary tumor, matched metastases, and matched adjacent tissues derived from 32 RCC patients. TOLLIP expression in tumor samples was evaluated using the H-score. All examined samples showed cytoplasmic TOLLIP expression, with a median value of 100 in primary tumors, 107.5 in metastases, and 220 in the control group. The expression was significantly higher in the normal adjacent tissues compared to primary or metastatic RCC (p < 0.05). We found a positive correlation between expressions of TOLLIP in the primary tumor and its metastases (p < 0.05; k = 0.48). TOLLIP expression significantly correlates with a lower overall survival rate (p = 0.047). TOLLIP functions as a ubiquitin-LC3 adaptor in the intracellular pathway associated with autophagy. Relative TOLLIP overexpression may augment autophagy-related signaling, limiting susceptibility to therapy. The blockade of TOLLIP physiological function seems to be a promising approach to overcoming resistance to systemic therapy.

Overexpression of kif11 is a poor prognostic factor in clear cell renal cell carcinoma.

INTRODUCTION: Unresectable renal cell carcinoma continues to be a great challenge due to our limited understanding of its underlying pathophysiology. We explored the relationship between KIF11 protein expression and the clinical courses of clear cell renal cell carcinoma (ccRCC) using a tissue microarray. MATERIAL AND METHODS: The tissue microarray contained specimens derived from 90 patients, cancer and matched adjacent non-cancerous tissue (2 cores per case), followed up for 7 years. Tumour samples were evaluated for KIF11 expression using the H-score, and their correlations with clinicopathological data and survival data were analysed. RESULTS: 72.7% of ccRCC tissues presented KIF11 cytoplasmic expression with a median value of 20 (interquartile range 0-200). The nuclear staining was positive in 36.36% of ccRCC tissues. Among controls, nuclear KIF11 expression was absent, but cytoplasmic expression was identified in all cases, with a median value of 230 (interquartile range 45-290). Cytoplasmic KIF11 expression in ccRCC tissues was lower than in the control tissues and was positively correlated with tumour grade and mortality (p < 0.05). KIF11 nuclear expression did not correlate with overall survival. CONCLUSIONS: Elevated expression of KIF11 predicts poor clinical outcome in ccRCC patients. Downregulation of KIF11 may provide a new therapeutic strategy for ccRCC.

Prognostic significance of SDF-1 chemokine and its receptors CXCR4 and CXCR7 involved in EMT of prostate cancer.

Tendency to conversion from state of chronic inflammation to malignancy is a tumor characteristic trait, which encourages progression to its metastatic stage.. The inflammatory cells maintaining in the tumor inaugurate a communication with cancer cells and become tumor-fostering cells. Epithelial-mesenchymal transition (EMT) is a program supporting malignant cells during switch phenotype into metastatic form, providing looseness of cell-cell adherence and strengthens migratory or invasive features. EMT-undergone tumor cells become more aggressive and resistant to apoptosis. Additionally, malignant cells can be stimulated to manufacture proinflammatory factors throughout EMT program. Chronic inflammation is responsible for EMT induction in malignancies. Developed tumors induce inflammatory response through excretion of cytokines, chemokines and growth factors, which recruit populations of infiltrating immune cells straight to the tumor microenvironment. The inflammatory reaction potentially exerts tumor control, but instead it can be intercepted by the tumor to stimulate its own development in direction to metastatic form. Our study confirmed that SDF-1 chemokine and its receptors, CXCR4 and CXCR7 may participate in initiation of metastases formation and EMT process.

Clear phylogeographic pattern and genetic structure of wild boar Sus scrofa population in Central and Eastern Europe.

The wild boar Sus scrofa is one of the widely spread ungulate species in Europe, yet the origin and genetic structure of the population inhabiting Central and Eastern Europe are not well recognized. We analysed 101 newly obtained sequences of complete mtDNA genomes and 548 D-loop sequences of the species and combined them with previously published data. We identified five phylogenetic clades in Europe with clear phylogeographic pattern. Two of them occurred mainly in western and central part of the continent, while the range of the third clade covered North-Eastern, Central and South-Eastern Europe. The two other clades had rather restricted distribution. In Central Europe, we identified a contact zone of three mtDNA clades. Population genetic structure reflected clear phylogeographic pattern of wild boar in this part of Europe. The contribution of lineages originating from the southern (Dinaric-Balkan) and eastern (northern cost of the Black Sea) areas to the observed phylogeographic pattern of the species in Central and Eastern Europe was larger than those from the regions located in southern France, Iberian, and Italian Peninsulas. The present work was the first mitogenomic analysis conducted in Central and Eastern Europe to study genetic diversity and structure of wild boar population.

TRIP13 predicts poor prognosis in clear cell renal cell carcinoma.

What is the leading molecular mechanism that causes broad resistance to systemic therapies remains a key question in renal cancer related research. We explored associations of TRIP13 expression with the clinical course using the tissue microarray (TMA). The TMA contained specimens from 87 patients diagnosed with clear cell renal cell carcinoma (ccRCC). We performed immunohistochemistry to investigate TRIP13 protein expression levels. The overall survival (OS) was analyzed using the Kaplan-Meier method and log-rank statistics. Univariate and multivariate analyses were conducted using Cox proportional hazard models. Median follow up for the TMA cohort was 7.0 years. Tissues from 28.74% of patients demonstrated high TRIP13 expression. Mean TRIP13 expression in TRIP13-rich tumors was significantly higher comparing to adjacent normal tissues (P < 0.05). TRIP13 expression did not significantly correlate with stage nor tumor grade (P > 0.05). Elevated expression of TRIP13 served as an independent unfavorable prognostic indicator of survival in ccRCC (P < 0.05). TRIP13 overexpression predicts poor prognosis in ccRCC. Together with the emerging reports, this observation raises a suspicion that TRIP13 is a substantial driver of resistance to systemic therapies against kidney cancer.