MOLECULAR EFFECTS OF AMINE DERIVATIVES OF PHENOTHIAZINE ON CANCER CELLS C-32 AND SNB-19 IN VITRO.

Cancer therapy is challenging for scientists because of low effectiveness of so far existing therapies (especially in case of great invasiveness and advanced tumor stage). Such need for new drug development and search for more efficient new findings in therapeutical applications is therefore still valid. There are also conducted studies on modifying so far existing drugs and their new methods of usage in oncology practice. One of them is phenothiazine and its derivatives which are used in psychiatric treatment for years. They also exhibit antiprion, antiviral, antibacterial and antiprotozoal properties. Cytotoxic activity, influence on proliferation, ability to induce apoptosis suggest also a possibility of phenothiazine derivatives usage in cancer cells termination. The aim of our the study was to evaluate the influence of two amine derivatives of phenothiazine on cancer cells in vitro. Amelanotic melanoma C-32 cell line (ATCC) and glioma SNB-19 cells (DSMZ) were used in this study and two derivatives were analyzed. In view of examined substances tumor potential toxicity cells proliferation and viability exposed to phenothiazine derivatives were established. Cell cycle regulatory genes expression (TP53 and CDKN1A), S-phase marker--H3 gene and intracellular apoptosis pathway genes (BAX, BCL-2) were analyzed using RT-QPCR method. The influence of examined derivatives on total cell oxidative status (TOS), total antioxidative status (TAS), malondialdehyde concentration (MDA) and superoxide dismutase activity (SOD) were analyzed. As a result, examined phenothiazine derivatives cytotoxic action on C-32 and SNB-19 and also cells proliferation inhibition were determined. Cell cycle regulatory genes (TP53, CDKN1A) expression and protein products of genes involved in mitochondial apoptosis pathway (BAX, BCL-2) expression are changed by the presence of phenothiazine derivatives during culturing. There were also noted small changes in redox potential in cells exposed to two mentioned phenothiazine derivatives.

[Relation between local CMV infection and inflammatory cytokine expressionon in pts sheduled for CABG]. / Obecnosc wirusa cytomegalii w obrebie sciany aorty a miejscowa aktywacja zapalna u pacjentów z przewlekla choroba wiencowa poddawanych zabiegowi pomostowania aortalno-wiencowego.

INTRODUCTION: Cytomegalovirus (CMV) infection has been suggested to play a role in the development of cardiovascular diseases. It has not yet been established yet whether the possible adverse vascular effect is associated with chronic inflammation process caused by CMV. The aim of our study was to evaluate a possible role of CMV infection in local inflammatory activation in pts with coronary artery disease (CAD). MATERIAL AND METHODS: We enrolled 55 patients (mean age 62 years, 42 males, 13 females) with angiographically proven CAD scheduled for CABG surgery. Vessel specimens retrieved from ascending aorta (as a part of routine proximal venous graft development procedure) and peripheral blood mononuclear cells (PBMC) were evaluated for the transcriptional activity of IL-6 and TNF-alpha (the key cytokines involved in atherosclerosis) and for CMV DNA presence. Polymerase chain reaction reaction was performed in order to detect DNA of CMV as well as IL-6 and TNF-alpha transcriptional activity. RESULTS: CMV was present in 67.3% of aortic and in 60% of blood specimens accordingly; median level in aorta tissues: 114.63 +/- 116.54, PBMC: 107.89 +/- 132.39; non statistically significant (NS). An inflammatory response expressed as IL-6 and TNF-alpha transcriptional activity equaled in aorta 159.93 +/- 120.15, 299.55 +/- 154.89 and in PBMC: 190.85 +/- 122.08, 249.64 +/- 32.4; (NS). CMV DNA in PBMC was associated with CMV DNA in aortal tissue p = 0.0049. The analysis revealed positive correlation between IL-6 transcriptional activity and CMV DNA titer in aortic samples R = 0.35, p = 0.036. There were no statistically significant correlations between TNF-alpha transcriptional levels and CMV DNA concentration. Statistical analysis was made by use of Statistica 8.0; StatSoft program. We used arithmetical mean value, standard deviation, Spearmann correlation, X2 and U Mann-Whitney test. CONCLUSIONS: A local inflammatory response expressed against CMV could be a marker of longstanding inflammatory response that eventually would cause advanced clinical atherosclerosis. Our findings support the infectious theory and an association between CMV infection and atherosclerosis.

Cytomegalovirus infection in acute myocardial infarction. Is there a causative relationship?

BACKGROUND: Cytomegalovirus (CMV) infection has been suggested to play an important role in the pathogenesis of atherosclerosis. Whether CMV may be involved in the development of acute myocardial infarction (MI) has not yet been established. AIM: To asses the prevalence of active or latent CMV infection in patients with angina or acute MI. METHODS: The study group consisted of 158 subjects divided into three groups: group I - 70 patients (49 males, mean age 57.1+/-10.4 years) with acute MI, group II - 40 patients (21 males, mean age 59.1+/-7.9 years) with stable angina, and group III - 48 healthy controls (18 males, mean age 54.9+/-12.1 years). Anti-CMV IgM and IgG antibody titre in blood serum was measured in all subjects. In those in whom anti-CMV antibodies were present, quantitative polimerase chain reaction (Q-PCR) was performed in order to detect DNA of CMV in peripheral blood mono-nuclear cells (PBMC) and in serum. RESULTS: Anti-CMV IgM antibodies were not detected in any of the subjects. A positive result of anti-CMV IgG test was present in 60 (85.7%) patients from group I, 34 (85%) patients from group II, and 15 (31.5%) control subjects. The mean IgG antibody concentration was 72.2+/-13.6 aU/ml, 74.23+/-12.8 aU/ml and 19.57+/-3.56 aU/ml, respectively (p<0.001). In patients from group I, a significantly higher prevalence of serum DNA CMV was noted than in the remaining groups. CONCLUSIONS: Patients with symptomatic coronary artery disease have a significantly higher anti-CMV antibody titre than healthy subjects. The active form of infection is significantly more prevalent in patients with acute MI than in patients with stable angina.