Present state and possibilities for improvement of cancer prevention and early detection in the Osijek-Baranya county

Cancer morbidity and mortality are on a steady increase in Croatia. Technologic possibilities for appropriate management are available for four cancer sites, i.e. cancer of the breast, cervix uteri, colorectum and prostate, and include cancer prevention and early detection in individuals yet free from manifest signs of the disease. The magnitude of the problem, the experience acquired to date, health care personnel available, and additional resources required to launch a systematic program of early detection of the disease are presented. The program should be initially launched in a county with greatest experience in early detection of cancer, where health care service is ready to immediately start its implementation. The role of family physician, gynecologic service at primary health care level, and polyclinic-consultation hospital service in program implementation is described. The following three possible options for early detection of cancer are analyzed and proposed: minimal program (early detection every 3 years), medium program (the same individuals examined every 2 years), and optimal program proposed by the American Cancer Society and other national and international organizations.     

Modulation of the heart rate by thyroid hormone in the newborn rat

Confirming the literature data the authors describe that the heart rate is smaller in the newborn rats than in adult ones and increases until the adult values during the first two weeks of life. On the other hand, the blood thyroid hormone exhibits the same pattern, showing an early postnatal increment. As, according the Adolph's data (1967), the heart rate enhancement is not due to the catecholamines, the authors suppose that such enhancement might conceivably depend on thyroid hormone increment.     

In Vitro and In Vivo Antitumor Activity of [Pt(O,O′-acac)(γ-acac)(DMS)] in Malignant Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is an aggressive malignancy highly resistant to chemotherapy. There is an urgent need for effective therapy inasmuch as resistance, intrinsic and acquired, to conventional therapies is common. Among Pt(II) antitumor drugs, [Pt(O,O′-acac)(γ-acac)(DMS)] (Ptac2S) has recently attracted considerable attention due to its strong in vitro and in vivo antiproliferative activity and reduced toxicity. The purpose of this study was to examine the efficacy of Ptac2S treatment in MPM. We employed the ZL55 human mesothelioma cell line in vitro and in a murine xenograft model in vivo, to test the antitumor activity of Ptac2S. Cytotoxicity assays and Western blottings of different apoptosis and survival proteins were thus performed. Ptac2S increases MPM cell death in vitro and in vivo compared with cisplatin. Ptac2S was more efficacious than cisplatin also in inducing apoptosis characterized by: (a) mitochondria depolarization, (b) increase of bax expression and its cytosol-to-mitochondria translocation and decrease of Bcl-2 expression, (c) activation of caspase-7 and -9. Ptac2S activated full-length PKC-δ and generated a PKC-δ fragment. Full-length PKC-δ translocated to the nucleus and membrane, whilst PKC-δ fragment concentrated to mitochondria. Ptac2S was also responsible for the PKC-ε activation that provoked phosphorylation of p38. Both PKC-δ and PKC-ε inhibition (by PKC–siRNA) reduced the apoptotic death of ZL55 cells. Altogether, our results confirm that Ptac2S is a promising therapeutic agent for malignant mesothelioma, providing a solid starting point for its validation as a suitable candidate for further pharmacological testing.     

Identification of PR-SET7 and EZH2 selective inhibitors inducing cell death in human leukemia U937 cells

Chemical manipulations undertaken on some bis(bromo- and dibromo-phenol) compounds previously reported by us as wide-spectrum epigenetic inhibitors let us to identify bis (bromo- and dibromo-methoxyphenyl) derivatives highly selective for PR-SET7 and EZH2 (compounds 4, 5, 9, and 10). Western blot analyses were carried out in U937 cells to determine the effects of such compounds on the methyl marks related to the tested enzymes (H3K4me1, H3K9me2, H4H20me1, and H3K27me3). The 1,5-bis(3-bromo-4-methoxyphenyl)penta-1,4-dien-3-one 4 (EC₅₀ vs EZH2 = 74.9 μM), tested in U937 cells at 50 μM, induced massive cell death and 28% of granulocytic differentiation, highlighting the potential use of EZH2 inhibitors in cancer.     

Dissecting NK cell development using a novel alymphoid mouse model: investigating the role of the c-abl proto-oncogene in murine NK cell differentiation

NK lymphocytes participate in both innate and adaptive immunity by their prompt secretion of cytokines including IFN-gamma, which activates macrophages, and by their ability to lyse virally infected cells and tumor cells without prior sensitization. Although these characteristics of NK cells are well documented, little is known about the genetic program that orchestrates NK development or about the signaling pathways that trigger NK effector functions. By crossing NK-deficient common gamma-chain (gammac) and recombinase activating gene (RAG)-2 mutant mice, we have generated a novel alymphoid (B-, T-, and NK-) mouse strain (RAG2/gammac) suitable for NK complementation in vivo. The role of the c-abl proto-oncogene in murine NK cell differentiation has been addressed in hemopoietic chimeras generated using RAG2/gammac mice reconstituted with c-abl-/- fetal liver cells. The phenotypically mature NK cells that developed in the absence of c-abl were capable of lysing tumor targets, recognizing "missing self," and performing Ab-dependent cellular cytotoxicity. Taken together, these results exclude any essential role for c-abl in murine NK cell differentiation in vivo. The RAG2/gammac model thereby provides a novel approach to establish a genetic map of NK cell development.     

Interactions ofCandida albicans with bacteria and salivary molecules in oral biofilms

The yeastCandida albicans coaggregates with a variety of streptococcal species, an interaction that may promote oral colonization by yeast cells.C. albicans andCandida tropicalis are the yeasts most frequently isolated from the human oral cavity and our data demonstrate that both these species bind toStreptococcus gordonii NCTC 7869 while two otherCandida species (Candida krusei andCandida kefyr) do not. Adherence ofC. albicans was greatest when the yeast had been grown at 30° C to mid-exponential growth phase. For 21 strains ofC. albicans there was a positive correlation between the ability to adhere toS. gordonii and adherence to experimental salivary pellicle. Whole saliva either stimulated or slightly inhibited adherence ofC. albicans toS. gordonii depending on the streptococcal growth conditions. The results suggest that the major salivary adhesins and coaggregation adhesins ofC. albicans are co-expressed.