Cancer Microenvironment and Inflammation: Role of Hyaluronan

The role of inflammation in the development of cancer was described as early as 19th century. Abundant evidence supports the preposition that various cancers are triggered by infection and chronic inflammatory disease whereas, evading immune destruction has been proposed as one of the new hallmarks of cancer. Changes of the tumor microenvironment have been closely correlated to cancer-mediated inflammation. Hyaluronan (HA), an important ECM component, has become recognized as an active participant in inflammatory, angiogenic, fibrotic, and cancer promoting processes. This review discusses how HA and specific HA-binding proteins participate in and regulate cancer-related inflammatory processes

Treatment of pathologic spinal fractures with combined radiofrequency ablation and balloon kyphoplasty

<p>Abstract</p> <p>Background</p> <p>In oncologic patients with metastatic spinal disease, the ideal treatment should be well tolerated, relieve the pain, and preserve or restore the neurological function.</p> <p>The combination of fluoroscopic guided radiofrequency ablation (RFA) and kyphoplasty may fulfill these criteria.</p> <p>Methods</p> <p>We describe three pathological vertebral fractures treated with a combination of fluoroscopic guided RFA and kyphoplasty in one session: a 62-year-old man suffering from a painful L4 pathological fracture due to a plasmocytoma, a 68-year-old man with a T12 pathological fracture from metastatic hepatocellular carcinoma, and a 71-year-old man with a Th12 and L1 pathological fracture from multiple myeloma.</p> <p>Results</p> <p>The choice of patients was carried out according to the classification of Tomita. Visual analog score (VAS) and Oswestry disability index (ODI) were used for the evaluation of the functional outcomes. The treatment was successful in all patients and no complications were reported. The mean follow-up was 6 months. Marked pain relief and functional restoration was observed.</p> <p>Conclusion</p> <p>In our experience the treatment of pathologic spinal fractures with combined radiofrequency ablation and balloon kyphoplasty is safe and effective for immediate pain relief in painful spinal lesions in neurologically intact patients.</p

Spinal Chondrosarcoma: A Review

Chondrosarcoma is the third most common primary malignant bone tumor. Yet the spine represents the primary location in only 2% to 12% of these tumors. Almost all patients present with pain and a palpable mass. About 50% of patients present with neurologic symptoms. Chemotherapy and radiotherapy are generally unsuccessful while surgical resection is the treatment of choice. Early diagnosis and careful surgical staging are important to achieve adequate management. This paper provides an overview of the histopathological classification, clinical presentation, and diagnostic procedures regarding spinal chondrosarcoma. We highlight specific treatment modalities and discuss which is truly the most suitable approach for these tumors. Abstracts and original articles in English investigating these tumors were searched and analyzed with the use of the PubMed and Scopus databases with “chondrosarcoma and spine” as keywords

Proteoglycans and Immunobiology of Cancer—Therapeutic Implications

Disparity during the resolution of inflammation is closely related with the initiation and progression of the tumorigenesis. The transformed cells, through continuously evolving interactions, participate in various exchanges with the surrounding microenvironment consisting of extracellular matrix (ECM) components, cytokines embedded in the ECM, as well as the stromal cells. Proteoglycans (PGs), complex molecules consisting of a protein core into which one or more glycosaminoglycan (GAG) chains are covalently tethered, are important regulators of the cell/matrix interface and, consecutively, biological functions. The discrete expression of PGs and their interacting partners has been distinguished as specific for disease development in diverse cancer types. In this mini-review, we will critically discuss the roles of PGs in the complex processes of cancer-associated modulation of the immune response and analyze their mechanisms of action. A deeper understanding of mechanisms which are capable of regulating the immune response could be harnessed to treat malignant disease

Insulin-Like Growth Factor and Epidermal Growth Factor Signaling in Breast Cancer Cell Growth: Focus on Endocrine Resistant Disease

Breast cancer is the most common type of cancer for women worldwide with a lifetime risk amounting to a staggering total of 10%. It is well established that the endogenous synthesis of insulin-like growth factor (IGF) and epidermal growth factor (EGF) polypeptide growth factors are closely correlated to malignant transformation and all the steps of the breast cancer metastatic cascade. Numerous studies have demonstrated that both estrogens and growth factors stimulate the proliferation of steroid-dependent tumor cells, and that the interaction between these signaling pathways occurs at several levels. Importantly, the majority of breast cancer cases are estrogen receptor-(ER-) positive which have a more favorable prognosis and pattern of recurrence with endocrine therapy being the backbone of treatment. Unfortunately, the majority of patients progress to endocrine therapy resistant disease (acquired resistance) whereas a proportion of patients may fail to respond to initial therapy (de novo resistance). The IGF-I and EGF downstream signaling pathways are closely involved in the process of progression to therapy resistant disease. Modifications in the bioavailability of these growth factors contribute critically to disease progression. In the present review therefore, we will discuss in depth how IGF and EGF signaling participate in breast cancer pathogenesis and progression to endocrine resistant disease

Biglycan Regulates MG63 Osteosarcoma Cell Growth Through a LPR6/β-Catenin/IGFR-IR Signaling Axis

Biglycan, a small leucine rich proteoglycan (SLRP), is an important participant in bone homeostasis and development as well as in bone pathology. In the present study biglycan was identified as a positive regulator of MG63 osteosarcoma cell growth (p ≤ 0.001). IGF-I was shown to increase biglycan expression (p ≤ 0.01), whereas biglycan-deficiency attenuated significantly both basal and IGF-I induced cell proliferation of MG63 cells (p ≤ 0.001; p ≤ 0.01, respectively). These effects were executed through the IGF-IR receptor whose activation was strongly attenuated (p ≤ 0.01) in biglycan-deficient MG63 cells. Biglycan, previously shown to regulate Wnt/β-catenin pathway, was demonstrated to induce a significant increase in β-catenin protein expression evident at cytoplasmic (p ≤ 0.01), membrane (p ≤ 0.01), and nucleus fractions in MG63 cells (p ≤ 0.05). As demonstrated by immunofluorescence, increase in β-catenin expression is attributed to co-localization of biglycan with the Wnt co-receptor low-density lipoprotein receptor-related protein 6 (LRP6) resulting in attenuated β-catenin degradation. Furthermore, applying anti-β-catenin and anti-pIGF-IR antibodies to MG-63 cells demonstrated a cytoplasmic and to the membrane interaction between these molecules that increased upon exogenous biglycan treatment. In parallel, the downregulation of biglycan significantly inhibited both basal and IGF-I-dependent ERK1/2 activation, (p ≤ 0.001). In summary, we report a novel mechanism where biglycan through a LRP6/β-catenin/IGF-IR signaling axis enhances osteosarcoma cell growth

Inflammation and Metabolism in Cancer Cell—Mitochondria Key Player

Cancer metabolism is an essential aspect of tumorigenesis, as cancer cells have increased energy requirements in comparison to normal cells. Thus, an enhanced metabolism is needed in order to accommodate tumor cells' accelerated biological functions, including increased proliferation, vigorous migration during metastasis, and adaptation to different tissues from the primary invasion site. In this context, the assessment of tumor cell metabolic pathways generates crucial data pertaining to the mechanisms through which tumor cells survive and grow in a milieu of host defense mechanisms. Indeed, various studies have demonstrated that the metabolic signature of tumors is heterogeneous. Furthermore, these metabolic changes induce the exacerbated production of several molecules, which result in alterations that aid an inflammatory milieu. The therapeutic armentarium for oncology should thus include metabolic and inflammation regulators. Our expanding knowledge of the metabolic behavior of tumor cells, whether from solid tumors or hematologic malignancies, may provide the basis for the development of tailor-made cancer therapies

Sol–Gel Synthesis and Characterization of YSZ Nanofillers for Dental Cements at Different Temperatures

From MDPI via Jisc Publications RouterHistory: accepted 2021-10-26, pub-electronic 2021-10-29Publication status: PublishedFunder: The project is co-financed by Greece and the EuropeanUnion (European Social Fund-ESF) by the Operational Program Human Resources Development,Education and Lifelong Learning 2014–2020.; Grant(s): MIS5047876Background: Yttria-stabilized zirconia nanoparticles can be applied as fillers to improve the mechanical and antibacterial properties of luting cement. The aim of this study was to synthesize yttria-stabilized zirconia nanoparticles by the sol–gel method and to investigate their composition, structure, morphology and biological properties. Methods: Nanopowders of ZrO2 7 wt% Y2O3 (nY-ZrO) were synthesized by the sol–gel method and were sintered at three different temperatures: 800, 1000 and 1200 °C, and their composition, size and morphology were investigated. The biocompatibility was investigated with human gingival fibroblasts (hGFs), while reactive oxygen species (ROS) production was evaluated through fluorescence analysis. Results: All synthesized materials were composed of tetragonal zirconia, while nanopowders sintered at 800 °C and 1000 °C additionally contained 5 and 20 wt% of the cubic phase. By increasing the calcination temperature, the crystalline size of the nanoparticles increased from 12.1 nm for nY-ZrO800 to 47.2 nm for nY-ZrO1200. Nano-sized particles with good dispersion and low agglomeration were received. Cell culture studies with human gingival fibroblasts verified the nanopowders’ biocompatibility and their ROS scavenging activity. Conclusions: the obtained sol–gel derived nanopowders showed suitable properties to be potentially used as nanofillers for dental luting cement

Specific Syndecan-1 Domains Regulate Mesenchymal Tumor Cell Adhesion, Motility and Migration

Malignant mesothelioma is an asbestos induced cancer that is difficult to diagnose. Several studies have combined biomarkers to improve mesothelioma diagnosis, but with moderate success, and there is a need for new mesothelioma biomarkers. The tumour is often resistant to treatment and most patients will survive less than a year. An indicator of patient survival is the tumours growth pattern, which in turn is influenced by expressed proteoglycans. In this thesis work, we aim to improve the possibilities to diagnose malignant mesothelioma by combining biomarkers and by identifying new ones. We also investigate tumour driving mechanisms with focus on one of these suggested biomarkers, the cell-bound proteoglycan syndecan-1. We were able to construct a diagnostic two-step model based on biomarkers in patient material. By implementing a cut-off level and thereafter focusing on unresolved patients we combined hyaluronan and N-ERC/mesothelin (paper I), which significantly increased the diagnostic accuracy for malignant mesothelioma. To further improve diagnosis, we used mass spectrometry to find new biomarkers. We identified and validated galectin-1, which was excellent in discriminating mesotheliomas from adenocarcinomas (paper II). In the same study, we were also the first to describe aldo-keto reductase 1B10 as a novel prognostic mesothelioma biomarker. Syndecan-1 has been indicated as a marker for carcinomas. In paper I we describe how higher levels of syndecan-1 indicate the presence of a carcinoma over a mesothelioma. This was verified in paper II when syndecan-1 was identified as downregulated in fluids from mesothelioma patients compared to lung cancer patients. Paper III and paper IV focus on this proteoglycan. Malignant cell lines transfected with syndecan-1 and various truncated forms of syndecan-1 affected adhesion and migration, which are key features of cancer invasion (paper III). The results showed a domain- and cell type specific effect on the cells’ motility. Regulating syndecan-1 levels and analysing the global gene expression of mesothelioma cells made it evident that this proteoglycan has a strong influence on transforming growth factor β signalling and several growth factor pathways (paper IV). Links to cell migration and proliferation were furthermore identified, along with glycosaminoglycan modifying enzymes. These results can shed light on the complex role of syndecan-1 in invasion and growth of malignant mesenchymal cells. Taken together, this thesis work describes a complement to conventional mesothelioma diagnosis and identifies novel biomarkers. Furthermore, the potential biomarker syndecan-1 was shown to have an effect on cell motility and proliferation. These results increase our understanding of this aggressive malignancy

Correlation of histological, biochemical and hematological findings after P. aeruginosa LPS administration in rats wistar: Experimental study

This work was undertaken in order to study the behaviour of three P. aeruginosa Lipopolysaccharides (smooth, rough and deep-rough) after intravenous injection (1.5 mg) in Wistar rats. For each lipopolysaccharide 18 experimental animals were allocated and sacrificed in groups of three at 1th, 2th, 4th and 24th hours, 3th and 7th day. The organs studied by the light microscopy were: heart, lung, liver, spleen, kidneys, adrenals and eyes. In addition the distribution of the three LPSs in the liver was studied with immunochemistry and sections of liver tissue were examined in ultrastractural microscope. Bone marrow was aspirated as well as collection of whole blood for haematological and biochemical tests. Examination of tissue sections by light microscopy revealed that the earliest lesions are located in the lung and involve focal areas of atelectasis as well as infiltration of the alveolar septa by polymorphonucleocytes resulting on the 3rd day to destruction of architectural structure by massive areas of atelectasis spleen is followed with infiltration of red pulp by polymorphonuclear and eosinophils. The liver with significant lesions, necrosis, bridging fibrosis (IR) and cytoplasmic vacuoles in hepatocytes. Adrenals with cytoplasmic vacuoles mainly in cells of the fascicular zone, and kidneys with necrosis of epithelial cells of the proximal convoluted tubules. Ultrastractural examination of the liver showed swollen mitochondria, dilated canaliculi, reduction of Hglycogen, prominent lysosomes and increased of fat. Immunoperoxidase studies of the LPS distribution in liver sections showed the smooth type LPS initially only in Kupffer cells, while the rough and the deep-rough LPS were located in Kupffer cells and hepatocytes simultaneously. Biochemical analysis of serum was related to tissue damage, while the bone marrow revealed stimulation from the first hour. The result of this study show that all three P. aeruginosa LPSs are toxic, with different time action (smooth LPS actives later than rough and deep-rough LPS, but remains longer in the cells of organs) and their different inherent distribution characteristics produces the respective lesions.Σκοπός της εργασίας αυτής ήταν η μελέτη της βιολογικής συμπεριφοράς τριών λιποπολυσακχαριτών (smooth, rough και deep-rough) Pseudomonas aeruginosa, μετά ενδοφλέβιο χορήγηση (1.5 mg) σε επίμυες Wistar. Για τον κάθε λιποπολυσακχαρίτη χρησιμοποιήθηκαν 18 πειραματόζωα, τα οποία θυσιάσθηκαν ανά τρία στο τέλος της 1ης, 2ης, 4ης, 24ης ώρας, 3ης και 7ης ημέρας. Τα όργανα που εξετάσθηκαν στο φωτονικό μικροσκόπιο ήταν: καρδιά, πνεύμων, ήπαρ, σπλην, νεφροί, επινεφρίδια και οφθαλμοί. Επί πλέον για το ήπαρ έγινε ανοσοϊστοχημική εξέταση της κατανομής των τριών λιποπολυσακχαριτών και ηλεκτρονική μικροσκοπία. Ελήφθη επίσης αίμα για αιματολογικό και βιοχημικό έλεγχο, καθώς και ο μυελός των οστών. Από την εξέταση των ιστολογικών τομών στο φωτονικό μικροσκόπιο προέκυψε ότι οι πρωϊμότερες αλλοιώσεις εντοπίζονται στον πνεύμονα και αφορούν εστίες ατελεκτασίας και διηθήσεως των κυψελιδικών διαφραγμάτων από πολυμορφοπύρηνα και ηωσινόφιλα. Το ήπαρ με σημαντικές αλλοιώσεις νεκρώσεως, γεφυροποιού ινώσεως (IR) και κυτταροπολασματικά κενοτόπια στα ηπατοκύτταρα. Τα επινεφρίδια με κενοτόπια κυρίως στα κύτταρα της στηλιδωτής ζώνης και .οι νεφροί με νέκρωση επιθηλιακών κυττάρων των εγγύς εσπειραμένων σωληναρίων. Η εξέταση του ήπατος στο ηλεκτρονικό μικροσκόπιο έδειξε διόγκωση των μιτοχονδρίων, διάταση των χοληφόρων τριχοειδών, πτώση του γλυκογόνου, εμφανή λυσοσώματα και αύξηση του λίπους. Η ανοσοϊστοχημική εξέταση της κατανομής της ενδοτοξίνης σε τομές ήπατος έδειξε αρχικά το smooth LPS μόνο στα κύτταρα Kupffer και ακολούθως στα ηπατοκύτταρα, ενώ ο rough και ο deep-rough LPS εντοπίσθηκε από την αρχή τόσο στα κύτταρα Kupffer όσο και στα ηπατοκύτταρα. Η βιοχημική ανάλυση του πλάσματος ήταν ανάλογη της ιστικής βλάβης, ενώ ο μυελός των οστών εμφάνισε στοιχεία ενεργοποιήσεως από την 1η ώρα. Τα ευρήματα της μελέτης αυτής δείχνουν ότι και οι τρείς τύποι HLPS της P. aeruginosa είναι τοξικοί, έχουν διαφορετικό χρόνο δράσεως (ο smooth δρα αργότερα από τον rough και τον deep-rough, αλλά παραμένει περισσότερο χρόνο στα κύτταρα των οργάνων) και η διαφορά της κυτταρικής τους κατανομής δημιουργεί τις αντίστοιχες αλλοιώσεις