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Abstract: Osteopontin (OPN) is a glycoprotein involved in invasion, progression and metastasis of many carcinomas. It contains several functional domains including binding sites for αv integrins, cell surface molecules playing a major role in mediating cell migration and adhesion. The aim of the study was to evaluate the expression of osteopontin in human non-small cell lung cancer (NSCLC) and to determine its possible prognostic significance as well as relation to apoptosis and αv integrin expression. We analyzed 111 surgically resected NSCLC for immunohistochemical expression of OPN and αv integrin. OPN expression was compared to apoptotic rate and clinicopathological parameters such as tumor size, histological grade, lymph node status, pT, and TNM stage. Apoptotic rate was measured by TUNEL staining method. OPN expression in NSCLC was significantly higher in lung adenocarcinomas (AC) then in squamous cell carcinomas (p <0.001). There was no correlation between OPN expression and clinicopathological parameters. The level of OPN expression in AC was associated with decreased apoptotic activity of tumor cells (p =0.006), and correlated with αv integrin expression (p =0.048), particularly in low stage tumors (p =0.013). Prolonged tumor cell survival in lung AC due to OPN and αv integrin overexpression may have an impact on tumor progression and resistance to therapy. [Copyright &y& Elsevier]

Abstract: Osteopontin (OPN) is a phosphoglycoprotein implicated in tumorigenesis and tumor cell metastasis. Apoptosis inhibition is one of the mechanisms that contribute to development and progression of cancer, and might be initiated by OPN interaction with tumor cells. The aim of this study was to analyze the relation between OPN and nuclear factor-kappa B (NF-κB) expression in clear cell renal cell carcinoma (CCRCC), as well as their relation to apoptotic activity of tumor cells. Expression of OPN protein and p65 NF-κB subunit was analyzed immunohistochemically in 87 CCRCC samples, and compared mutually and with apoptotic index. Expression of OPN mRNA was analyzed using quantitative real-time PCR and compared with OPN and NF-κB protein expression in 22 CCRCC samples. Statistical analysis showed an association of p65 NF-κB with OPN mRNA (p =0.015) and protein (p <0.001). Also, we found an inverse relationship of OPN with NF-κB protein expression and apoptotic activity of tumor cells (p =0.006 and p =0.022, respectively). Our results indicate that p65 NF-κB signaling pathway may be involved in OPN-mediated CCRCC progression, partly by protecting tumor cells from apoptosis. Therefore, both molecules can constitute potential targets for therapeutic intervention in CCRCC. [Copyright &y& Elsevier]

Sudden cardiac death (SCD) is an unexpected natural death of cardiac etiology and occurs within one hour of the onset of cardiac symptoms in an apparently healthy subject or within 24 h if death is not witnessed. The diagnosis of early myocardial ischemia (EMI) or acute myocardial infarction (AMI) after death is a challenge for forensic pathologists especially when death occurs in a short period of time after the onset of myocardial ischemia. Disorder of cardiomyocytes Ca2+ homeostasis caused by myocardial ischemia during SCD can lead to the activation of calcium-activated non-lysosomal cysteine protease, including calpains. They serve as a proteolytic unit for cell balance and also participate in the processes of apoptosis and necrosis. Agony is a period that precedes somatic death that differs from cellular agony which may evolve for hours after somatic death lasting differently depending on the cell type and mechanism of death. We hypothesize that the expression of calpain 2 in cardiomyocytes could be a specific and sensitive diagnostic forensic marker for SCD caused by EMI and an indicator of the duration of myocardial agonal period. We will conduct a retrospective study that will prove this hypothesis on the respondents who died of SCD by EMI and AMI, instant death by head gunshot and hanging. There is no data on such an analysis in the available literature. The standard hematoxylin-eosin staining will be used to detect cardiac tissue damage. The expression of calpain 2 in cardiomyocytes will be analyzed immunohistochemically. In SCD caused by EMI we expect lower level of calpain 2 expressionin comparison to AMI due to shorter duration of dying. Similar, we predict in the remote region lower calpain 2 expression than in the region of ischemia for both EMI and AMI. In instant death caused by perforating traumatic brain injury we expect mild or no calpain 2 expression throughout the whole myocardium because of very short (immediate) duration of dying. In death caused by hanging calpain 2 expression throughout the whole myocardium should be strong because of longer cellular agonal period. We expect that our results would indicate the immediate activation of calpain 2 in different causes of cardiomyocytes death. From the degree of expression of calpain 2 we could conclude about the duration of cardiomyocytes agony so calpain 2 could be used as a marker for the assessment the duration of somatic and cellular agony. [ABSTRACT FROM AUTHOR]