Integrated miRNA Profiling of Extracellular Vesicles from Uterine Aspirates, Malignant Ascites and Primary-Cultured Ascites Cells for Ovarian Cancer Screening.

Extracellular vesicles (EVs) are of growing interest in the context of screening for highly informative cancer markers. We have previously shown that uterine aspirate EVs (UA EVs) are a promising source of ovarian cancer (OC) diagnostic markers. In this study, we first conducted an integrative analysis of EV-miRNA profiles from UA, malignant ascitic fluid (AF), and a conditioned medium of cultured ascites cells (ACs).

Opposite Effects of CRABP1 and CRABP2 Homologs on Proliferation of Breast Cancer Cells and Their Sensitivity to Retinoic Acid.

Resistance of tumor cells to retinoic acid (RA), a promising therapeutic agent, is the major factor limiting the use of RA in clinical practice. The mechanisms of resistance to RA are still poorly understood. Cellular Retinoic Acid Binding Proteins, CRABP1 and CRABP2, are essential mediators of RA signaling, but role of the two CRABP homologs in regulating cellular sensitivity to RA has not been well studied.

Comparison of Methods for MicroRNA Isolation from Extracellular Vesicles Obtained from Ascitic Fluids.

Secreted extracellular vesicles (EVs) contain active biomolecules, including miRNAs, composition of which reflects epigenetic changes occurring in cells during pathological processes, in particular, malignant transformation. The accumulated pool of data on the role of EVs in carcinogenesis has stimulated investigations of the EV-derived cancer markers. The most important factor limiting development of this scientific direction is lack of "gold standards" both for methods of EV isolation from biological fluids and for analyzing their molecular content, including composition of miRNAs.

Isolation and Characterization of Extracellular Vesicles from Gastric Juice.

EVs are involved in local and distant intercellular communication and play a vital role in cancer development. Since EVs have been found in almost all body fluids, there are currently active attempts for their application in liquid diagnostics. Blood is the most commonly used source of EVs for the screening of cancer markers, although the percentage of tumor-derived EVs in the blood is extremely low.

CRABP1 and CRABP2 Protein Levels Correlate with Each Other but Do Not Correlate with Sensitivity of Breast Cancer Cells to Retinoic Acid.

Retinoic acid (RA) binding proteins, CRABP1 and CRABP2, are molecular chaperones that mediate intracellular activity of RA, the key promoter of cell differentiation with tumor suppressor activity. One of the main functions of CRABP2 is delivery and transfer of RA to the nuclear receptors RAR/RXR, which leads to activation of the transcription of a wide range of retinoid-responsive genes. The functions of CRABP1 are less studied but are apparently associated with sequestration of RA in cytoplasm and limitation of its transcriptional activity, suggesting involvement of this protein in the development of RA resistance.

Stomatin is highly expressed in exosomes of different origin and is a promising candidate as an exosomal marker.

Proteins involved in the organizing of lipid rafts can be found in exosomes, as shown for caveolin-1, and they could contribute to exosomal cargo sorting, as shown for flotillins. Stomatin belongs to the same stomatin/prohibitin/flotillin/HflK/C family of lipid rafts proteins, but it has never been studied in exosomes except for extracellular vesicles (EVs) originating from blood cells. Here we first show the presence of stomatin in exosomes produced by epithelial cancer cells (non-small cell lung cancer, breast, and ovarian cancer cells) as well as in EVs from biological fluids, including blood plasma, ascitic fluids, and uterine flushings.

Lipid Rafts in Exosome Biogenesis.

Exosomes (secreted extracellular vesicles formed in the intracellular vesicular transport system) play a crucial role in distant cell-cell communication. Exosomes transfer active forms of various biomolecules; the molecular composition of the exosomal cargo is a result of targeted selection and depends on the type of producer cells. The mechanisms underlying exosome formation and cargo selection are poorly understood.

The role of nano-perovskite in the negligible thorium release in seawater from Greek bauxite residue (red mud).

We present new data about the chemical and structural characteristics of bauxite residue (BR) from Greek Al industry, using a combination of microscopic, analytical, and spectroscopic techniques. SEM-EDS indicated a homogeneous dominant "Al-Fe-Ca-Ti-Si-Na-Cr matrix", appearing at the microscale. The bulk chemical analyses showed considerable levels of Th (111 μg g(-1)), along with minor U (15 μg g(-1)), which are responsible for radioactivity (355 and 133 Bq kg(-1) for (232)Th and (238)U, respectively) with a total dose rate of 295 nGy h(-1).

Human papillomavirus types 16 E1 mRNA is transcribed from P14 early promoter in cervical neoplasms.

High-risk human papillomavirus (HR-HPV) persistent infection is responsible for the development of the majority of cervical cancers. The therapy against HPV-associated cancer requires knowledge of the viral gene expression mechanisms. In this study, the polyadenylated polycistronic transcripts containing full-size E1ORF and produced from the early P14 promoter were detected for the first time in cervical tumors with episomal forms of the HPV16 genome.

Expression and clinical significance of CRABP1 and CRABP2 in non-small cell lung cancer.

The impairment of retinoic acid (RA)-dependent signaling is a frequent event during carcinogenesis. Cellular retinoic acid-binding proteins (CRABP1 and CRABP2) are important modulators of RA activity. Up to date, the role of these proteins in cancer progression remains poorly investigated.

CRABP1 provides high malignancy of transformed mesenchymal cells and contributes to the pathogenesis of mesenchymal and neuroendocrine tumors.

CRABP1 (cellular retinoic acid binding protein 1) belongs to the family of fatty acid binding proteins. Retinoic acid binding is the only known functional activity of this protein. The role of CRABP1 in human carcinogenesis remains poorly understood.

[Prediction of a non-small cell lung cancer sensitivity to cisplatin and paclitaxel based on the marker genes expression].

The goal of the present study was to define gene expression signatures that predict a chemosensitivity of non-small cell lung cancer (NSCLC) to cisplatin and paclitaxel. To generate set of candidate genes likely to be predictive a current knowledge of the pathways involved in resistance and sensitivity to individual drugs was used. Forty four genes coding proteins belonging to following categories: ATP-dependent transport proteins, detoxification system proteins, reparation system proteins, tubulin and proteins responsible for its synthesis, cell cycle and apoptosis proteins were considered.

Arf6 promotes cell proliferation via the PLD-mTORC1 and p38MAPK pathways.

The small G-protein ADP-ribosylation factor 6 (Arf6) belongs to the Ras GTPases superfamily and is mostly known for its actin remodeling functions and involvement in the processes of plasma membrane reorganization and vesicular transport. The majority of data indicates that Arf6 contributes to cancer progression through activation of cell motility and invasion. Alternatively, we found that the expression of a wild-type or a constitutively active Arf6 does not influence tumor cell motility and invasion but instead significantly stimulates cell proliferation and activates phospholipase D (PLD).

Different metastasis promotive potency of small G-proteins RalA and RalB in in vivo hamster tumor model.

Background: Previously we have shown that oncogenic Ha-Ras stimulated in vivo metastasis through RalGEF-Ral signaling. RalA and RalB are highly homologous small G proteins belonging to Ras superfamily. They can be activated by Ras-RalGEF signaling pathway and influence cellular growth and survival, motility, vesicular transport and tumor progression in humans and in animal models.

[Arf6, RalA and BIRC5 protein expression in non small cell lung cancer].

Evaluation of tumor markers expression pattern which determines individual progression parameters is one of the major topics in molecular oncopathology research. This work presents research on expression analysis of several Ras-Ral associated signal transduction pathway proteins (Arf6, RalA and BIRC5) in accordance with clinical criteria in non small cell lung cancer patients. Using Western-blot analysis and RT-PCR Arf6, RalA and BIRC5 expression has been analyzed in parallel in 53 non small cell lung cancer samples of different origin.

The small G-protein RalA stimulates metastasis of transformed cells.

RAS oncogenes play a critical role in oncogenic transformation and metastases formation. Here we show that Ha-ras greatly stimulates spontaneous metastatic activity of transformed cells through the Ras/RalGDS/RalA intracellular signaling pathway. Introduction of RalA alone leads to a drastic increase of metastatic activity of transformed cells.

Mechanisms of unusually high antioxidant activity of RSV-SR-transformed cells and of its suppression by activated p21ras.

We have previously demonstrated that hamster embryo fibroblasts (HEFs) transformed by Rous Sarcoma virus, Schmidt-Ruppin strain (RSV-SR) are highly resistant to damage by H202 (H2O2R), (in contrast to HEFs transformed spontaneously, or by bovine adenovirus and SV40), while N-ras transfection of RSV-SR transformants leads to suppression of pp6Ov-scr and of H2O2R. In this study we have examined (1) mechanisms of antioxidant activity (AOA) of HEFs transformed by these agents and (2) the possible role of the v-src gene in unusually high AOA of RSV-SR transformants and of activated ras oncogenes in its suppression. All transformants exhibit increased catalase and glutathione peroxidase (GP) activities, while SOD, glutathione and glutathione reductase (GR) were reduced.