The role of cancer-associated fibroblasts, solid stress and other microenvironmental factors in tumor progression and therapy resistance

Tumors are not merely masses of neoplastic cells but complex tissues composed of cellular and noncellular elements. This review provides recent data on the main components of a dynamic system, such as carcinoma associated fibroblasts that change the extracellular matrix (ECM) topology, induce stemness and promote metastasis-initiating cells. Altered production and characteristics of collagen, hyaluronan and other ECM proteins induce increased matrix stiffness. Stiffness along with tumor growth-induced solid stress and increased interstitial fluid pressure contribute to tumor progression and therapy resistance. Second, the role of immune cells, cytokines and chemokines is outlined. We discuss other noncellular characteristics of the tumor microenvironment such as hypoxia and extracellular pH in relation to neoangiogenesis. Overall, full understanding of the events driving the interactions between tumor cells and their environment is of crucial importance in overcoming treatment resistance and improving patient outcome

The Oncogenic Lipid Sphingosine-1-Phosphate Impedes the Phagocytosis of Tumor Cells by M1 Macrophages in Diffuse Large B Cell Lymphoma

Background: A total of 30–40% of diffuse large B cell lymphoma (DLBCL) patients will either not respond to the standard therapy or their disease will recur. The first-line treatment for DLBCL is rituximab and combination chemotherapy. This treatment involves the chemotherapy-induced recruitment of tumor-associated macrophages that recognize and kill rituximab-opsonized DLBCL cells. However, we lack insights into the factors responsible for the recruitment and functionality of macrophages in DLBCL tumors. Methods: We have studied the effects of the immunomodulatory lipid sphingosine-1-phosphate (S1P) on macrophage activity in DLBCL, both in vitro and in animal models. Results: We show that tumor-derived S1P mediates the chemoattraction of both monocytes and macrophages in vitro and in animal models, an effect that is dependent upon the S1P receptor S1PR1. However, S1P inhibited M1 macrophage-mediated phagocytosis of DLBCL tumor cells opsonized with the CD20 monoclonal antibodies rituximab and ofatumumab, an effect that could be reversed by an S1PR1 inhibitor. Conclusions: Our data show that S1P signaling can modulate macrophage recruitment and tumor cell killing by anti-CD20 monoclonal antibodies in DLBCL. The administration of S1PR1 inhibitors could enhance the phagocytosis of tumor cells and improve outcomes for patients

Two-dimensional quantitative near-field phase imaging using square and hexagonal interference devices

We demonstrate the formation of the near field with non-trivial phase distribution using surface plasmon interference devices, and experimental quantitative imaging of that phase with near-field phase microscopy. The phase distribution formed with a single device can be controlled by the polarization of the external illumination and the area of the device assigned to the object wave. A comparison of the experimental data to a numerical electromagnetic model and an analytical model assigns the origin of the near-field phase to the out-of-plane electric component of surface plasmon polaritons, and also verifies the predictive power of the models. We demonstrate a formation of near-field plane waves with different propagation directions on a single device, or even simultaneously at distinct areas of a single device. Our findings open the way to the imaging and tomography of phase objects in the near field

Telomere Attrition Occurs during Ex Vivo Expansion of Human Dental Pulp Stem Cells

We provide a detailed characteristic of stem cells isolated and expanded from the human dental pulp. Dental pulp stem cells express mesenchymal cell markers STRO-1, vimentin, CD29, CD44, CD73, CD90, CD166, and stem cell markers Sox2, nestin, and nucleostemin. They are multipotent as shown by their osteogenic and chondrogenic potential. We measured relative telomere length in 11 dental pulp stem cell lines at different passages by quantitative real-time PCR. Despite their large proliferative capacity, stable viability, phenotype, and genotype over prolonged cultivation, human dental pulp stem cells suffer from progressive telomere shortening over time they replicate in vitro. Relative telomere length (T/S) was inversely correlated with cumulative doubling time. Our findings indicate that excessive ex vivo expansion of adult stem cells should be reduced at minimum to avoid detrimental effects on telomere maintenance and measurement of telomere length should become a standard when certificating the status and replicative age of stem cells prior therapeutic applications

Novel markers for differentiation of lobular and ductal invasive breast carcinomas by laser microdissection and microarray analysis

BACKGROUND: Invasive ductal and lobular carcinomas (IDC and ILC) are the most common histological types of breast cancer. Clinical follow-up data and metastatic patterns suggest that the development and progression of these tumors are different. The aim of our study was to identify gene expression profiles of IDC and ILC in relation to normal breast epithelial cells. METHODS: We examined 30 samples (normal ductal and lobular cells from 10 patients, IDC cells from 5 patients, ILC cells from 5 patients) microdissected from cryosections of ten mastectomy specimens from postmenopausal patients. Fifty nanograms of total RNA were amplified and labeled by PCR and in vitro transcription. Samples were analysed upon Affymetrix U133 Plus 2.0 Arrays. The expression of seven differentially expressed genes (CDH1, EMP1, DDR1, DVL1, KRT5, KRT6, KRT17) was verified by immunohistochemistry on tissue microarrays. Expression of ASPN mRNA was validated by in situ hybridization on frozen sections, and CTHRC1, ASPN and COL3A1 were tested by PCR. RESULTS: Using GCOS pairwise comparison algorithm and rank products we have identified 84 named genes common to ILC versus normal cell types, 74 named genes common to IDC versus normal cell types, 78 named genes differentially expressed between normal ductal and lobular cells, and 28 named genes between IDC and ILC. Genes distinguishing between IDC and ILC are involved in epithelial-mesenchymal transition, TGF-beta and Wnt signaling. These changes were present in both tumor types but appeared to be more prominent in ILC. Immunohistochemistry for several novel markers (EMP1, DVL1, DDR1) distinguished large sets of IDC from ILC. CONCLUSION: IDC and ILC can be differentiated both at the gene and protein levels. In this study we report two candidate genes, asporin (ASPN) and collagen triple helix repeat containing 1 (CTHRC1) which might be significant in breast carcinogenesis. Besides E-cadherin, the proteins validated on tissue microarrays (EMP1, DVL1, DDR1) may represent novel immunohistochemical markers helpful in distinguishing between IDC and ILC. Further studies with larger sets of patients are needed to verify the gene expression profiles of various histological types of breast cancer in order to determine molecular subclassifications, prognosis and the optimum treatment strategies

Preparation methacrylic acid from isobutyric acid

Předmětem práce bylo studium adsorpce kyseliny isomáselné, methakrylové a látek, které vznikají při oxidační dehydrogenaci isomáselné kyseliny na methakrylovou kyselinu, na katalyzátorech této reakce. Byla využita metoda plynové chromatografie s vyhodnocováním naměřených dat pomocí Glueckaufovy metody.Dokončená práce s úspěšnou obhajobo

Catalytic oxidative dehydrogenytion of 2-methylpropanal to 2-methylpropenal in the gas phase

Katalyzátory na bázi solí kyseliny fosfomolybdenové se ukazují jako vhodné pro přípravu methakrylátů. V této práci byla studována oxidativní dehydrogenace 2 methylpropanalu na 2- methylpropenal, což je jeden z mezikroků při přípravě methakrylátů, na katalyzátoru Cs2HPMo12O40. Reakce na uvedeném katalyzátoru měla velmi vysokou selektivitu na požadovaný produkt.Dokončená práce s úspěšnou obhajobo

Similarities and dissimilarities in access of different Church institutions for pensioners

The first part of this bachelor thesis deals with a brief history charitable activities of two churches that are in our country significantly active in helping the seniors. The most important church provider of social services for the elderly is the Roman Catholic Church; the second one is the Evangelical Church.The chapter entitled "Characteristics of the approach in church homes for the elderly" provides a basic description of each approach in the surveyed areas of care. Within the Church's approach the emphasis has been placed on the care for the spiritual needs of the clients. The practical part compares the selected approach areas in four church homes for seniors, all founded by the Charity Czech republic and Diaconate of the Evangelical Church of Czech Brethren.The research is divided into two parts. The first one describes the nature of the services provided by selected church homes for the elderly in areas of social work, charity work and as a part of it also the care for the spiritual needs of seniors, activation programs and the availability of these devices in terms of regional, financial and capacity features.The second part illustrates various forms of the religious pluralism of the direct care workers. Its aim is to determine the influence of this religiosity on their perception of the importance of the care for the spiritual needs of their clients and to find out whether the employees are themselves involved in the care of the mentioned needs