PREDICTIVE POWER OF OXIDATIVE STRESS BIOMARKERS IN RECURRENCE AND SURVIVAL IN ADVANCED CERVICAL CANCER.

The aim of our study was to measure the levels of 8-hydroxy-2-deoxyguanosine, malondialdehyde, and antioxidant enzymes in patients with locally advanced cervical cancer prior to treatment to determine how these evaluated biomarkers are associated with cervical cancer recurrence and to estimate their potential in further research and clinical use. MATERIALS AND METHODS: The study included 45 female patients with newly diagnosed advanced cervical cancer who underwent concomitant chemoradiotherapy. The blood and urine samples were collected prior to treatment, between December 2013 and April 2016, and subsequent laboratory analysis was performed. After the medium follow-up of 29 months, the patients were divided into 3 groups according to the time of disease recurrence. A statistical analysis was performed in order to evaluate the relationship between the previously measured biomarkers and recurrence. RESULTS: Taken individually, the parameters of oxidative stress did not reveal significant differences between the three groups in our study. Nevertheless, the catalase and glutathione S-transferase activities were the best predictors of the recurrence. Based on the activities of these two oxidative enzymes, it was possible to separate the group of patients without recurrence after follow-up from the other two groups of patients with recurrent disease. CONCLUSIONS: The parameters of oxidative stress have a certain predictive value on the outcome of patients with advanced cervical cancer after concomitant chemo-radiotherapy.

Oxidative stress and its role in cancer.

Reactive oxygen species (ROS) can damage lipids, nucleic acids, and proteins, thereby altering their functions. When a balance between production of ROS and antioxidative defense is disturbed, state of oxidative stress occurs. Oxidative stress leads to many diseases. There are few biomarkers that are used for better understanding how oxidative stress is involved in cancer pathophysiology. This review focuses on 8-hidroxy-2-deoxyguanosine (8-OHdG) and antioxidative enzymes as biomarkers for measurement of oxidative stress in different types of cancer. This review also deals with the product of lipid peroxidation, malondialdehyde (MDA), and across a variety of cancers. To address this aim, analysis of studies of breast, prostate, lung, colon, cervical, ovarian, brain, bladder, renal, thyroid cancer, and chronic lymphocytic leukemia has been conducted. In general, levels of antioxidative enzymes are mostly lower in cancer patients, while 8-OHdG and MDA are higher. Further research is needed, with focus on correlation levels of these biomarkers and advancement of the disease. Moreover, all studies explored the idea of those biomarkers as a useful tool in determining the levels of oxidative stress. Some of the studies proposed their potential in defining the stage of tumor progression.

Lipid Peroxidation, Antioxidative Defense and Level of 8-hydroxy-2-deoxyguanosine in Cervical Cancer Patients.

BACKGROUND: Oxidative stress has been associated with cervical cancer. Our aim was to examine lipid peroxidation and the extent of oxidative stress in women diagnosed with different stages of cervical cancer in order to evaluate its potential role in the evolution of cancer. METHODS: We measured the concentration of thiobarbituric acid reactive substances, activities of antioxidative enzymes and 8-hydroxy-2-deoxyguanosine in 153 subjects. Enzymatic activity as well as TBARS concentration were measured spectrophotometrically, while 8-OHdG was determined by gas chromatography-mass spectrometry. PPatients were categorized: group II H-SIL; group III FIGO Ia-Ib and group IV FIGO IIa-IV. RESULTS: Our results showed highly significant increase in the level of lipid peroxidation in group IV when com pared to the control group, group II and group III (p<0.001). Activity of superoxide dismutase was also significantly higher in group IV when compared to control group (p<0.01), group II (p<0.01) and group III (p<0.05). Activity of catalase was also significantly higher in group IV when compared to control group (p<0.005), group II (p<0.005) and group III (p<0.05). Activity of glutathione-S-transferase was also significantly higher in group IV when compared to control group (p<0.05), group II (p<0.05) and group III (p<0.05). Activities of glutathione peroxidase and glutathione reductase showed no significant differences among the groups. Level of 8-OHdG was significantly higher in group IV than in the other groups (p<0.01). CONCLUSIONS: It can be concluded that oxidative stress is possibly involved in the pathogenesis of cervical cancer, demonstrated by increased lipid peroxidation and an altered antioxidant defense system and higher levels of 8-OHdG.

Hepcidin and iron metabolism disorders in patients with chronic kidney disease.

BACKGROUND/AIM: [corrected] Hepcidin may play a pathogenetic role in iron metobolism disorders. The aim of this study was to determine the correlation between hepcidin concentration and parameters of iron metabolism in patients with different stage of chronic kidney disease (CKD). METHODS: The study involved 104 patients with CKD: 64 on hemodialysis (HD) and 40 patients in pre-dialysis stadium (pre-HD) with adequate erythropoetin therapy and iron supplementation. The HD group was divided in four subgroups according to the level of serum ferritin (up to 100; 100-199; 200-499 and over 500 ng/mL). Parameters of anemia, iron status, in flamation and hepcidin level were evaluated. RESULTS: The HD patients had a significantly lower eritrocyte count, erythrocytes indexes, hemoglobin and transferrin saturation and significantly higher iron, ferritin, hepcidin and total iron binding capacity (TIBC). The HD subgroups up to 199 ng/mL of serum feritin had lower high-sensitivity C-reactive protein (hsCRP), iron and higher unbuffered iron binding capacity (UIBC), transferrin saturation and TIBC compared to the HD subgroups over 200 ng/mL. The lowest and the highest ferritin subgroups had the highest hepcidin level and it showed significant correlation with ferritin. CONCLUSION: Hepcidin may serve as a marker for better diagnosing and monitoring anemia and iron metabolism disorders in CKD.

The effect of ursodeoxycholic acid on oxidative stress level and DNase activity in rat liver after bile duct ligation.

Accumulation of hydrophobic bile acids (BAs) during cholestasis plays an important role in apoptosis initiation as well as oxidative stress increase in liver cells. Ursodeoxycholic acid (UDCA) acts as a protector in BA-induced cell injury.The aim of the study was to evaluate the effect of UDCA on oxidative stress level and DNase I and II activity caused by liver injury in bile duct ligation (BDL) rats.Wistar rats were divided in four groups: group 1, control (sham-operated); group 2, sham-operated and injected with UDCA (30 mg/kg); group 3,animals with BDL; and group 4,UDCA-treatedcholestatic rats. Animals were sacrificed after 9 days. Malondialdehyde (MDA; lipid peroxidation end-product) level and protein-molecule oxidative modification (carbonyl group content) significantly increased in BDL rat liver. Catalase (CAT) activity in liver tissue was found to be decreased in BDL rats. In addition, xanthine oxidase (XO) activity, which is thought to be one of the key enzymes producing reactive oxygen species, was found to be increased in the cholestatic group. The apoptotic effect in cholestasis was probably triggered by the increased activation of DNase I and II. The protective effect of UDCA on liver tissue damage in BDL rats, in comparison to cholestatic liver, were 1) decrease of MDA levels, 2) increased CAT activity, 3) reduced XO activity, and 4) effect on terminal apoptotic reaction, shown as a decrease in DNase I and II activity.Therefore, UDCA may be useful in the preservation of liver function in cholestasis treatment.

[Evaluation of coagulation factors in fresh frozen plasma treated with riboflavin and ultraviolet light].

BACKGROUND/AIM: Pathogen inactivation in blood products using riboflavin and ultraviolet (UV) light represents a proactive approach to blood safety, not only for known infectious agents but also for new ones or not yet recognized as threats to the blood supply. This method inactivates a virus, bacteria, fungus, or protozoan pathogen from the blood product without damaging its function or shelf-life. The aim of the study was to study the influence of photoinactivation using riboflavin on the concentration of coagulation factors and coagulation inhibitors in plasma that was treated before freezing. METHODS: The examination included 30 units of plasma, separated from whole blood donated by voluntary blood donors around 6 h from the moment of collection. They were treated by riboflavin (35 mL) and UV rays (6.24 J/mL, 265-370 nm) on Mirasol aparature (Caridian BCT Biotechnologies, USA) in approximate duration of 6 min. The samples for examining were taken before (K - control units) and after illumination (I - illuminated units). RESULTS: Comparing the middle values of coagulation factors in the control and illuminated units we noticed their statistically significant decrease in illuminated units (p < 0.001), but the activity of coagulation ones was still in the reference range. The most sensitive coagulation factors to photoinactivation were FVIII, FIX and FXI (21.99%, 20.54% and 17.26% loss, respectively). Anticoagulant factors were better preseved than coagulation factors. CONCLUSION: Plasma separated from whole blood donation within 6 h, treated with riboflavin and UV light within 6 h from separation and frozen at temperature below -30 degrees C within 24 h, shows good retention of pro- and anticoagulation activity.

Correlation of cell cycle regulatory proteins (p53 and p16(ink)4(a)) and bcl-2 oncoprotein with mitotic index and thickness of primary cutaneous malignant melanoma.

The purpose of the study was to determine the frequency of expression p53 and p16INK4a proteins and bcl-2 oncoprotein in malignant skin melanoma and to determine their correlation with the proliferative index and tumor thickness. The study involved 53 patients: 27 (51%) male and 26 (49%) female. Mitotic index showed a correlation with p53 protein expression, a negative correlation with p16INK4a protein expression. Statistically significant correlations were determined between the Breslow tumor thickness, Clark invasion level and p53 protein expression, as well as Breslow tumor thickness and bcl-2 oncoprotein expression (p<0.05), whereas there was no correlation between the p16INK4a protein expression and melanoma thicknes and Clark invasion level. Overexpression p53 protein and bcl-2 oncoprotein, with the loss p16INK4a protein of expression in the nodular melanoma, confirms a frequent loss of function of these tumor suppressor gene and oncogene, and indicates a vertical tumor growth phase. The loss of tumor suppression function the p53 protein and bcl-2 oncoprotein overexpression in cutaneous melanoma correlates with larger tumor thickness, whereas the overexpression of mutated p53 protein and loss p16INK4a protein of expression indicate a higher proliferative tumour potential. Therefore, these evaluated proteins may be the aggressive biological tumour activity markers.

[Serum concentration of soluble adhesive molecules in patients with different forms of coronary artery disease].

BACKGROUND/AIM: Vascular cell adhesion molecules-1 (VCAM-1) and intercellular cell adhesive molecules-1 (ICAM-1) play an important role in developing and progression of coronary atherosderosis. The aim of the paper was to compare concentrations of soluble forms of VCAM-1 and ICAM-1 in patients with different clinical presentations of coronary artery disease (CAD) and patients without CAD. METHODS: Blood samples were taken from 25 patients with acute myocardial infarction (AMI), 25 patients with unstable angina pectoris (UAP), 25 with stable angina pectoris (SAP) and from 15 control patients without CAD, and concentrations of solubile adhesive molecules (VCAM-1, ICAM-1) were determined. RESULTS: Obesity was more prominent in the NAP than in the SAP and the control patients (p < 0.05). There were no significant differences in gender distribution, age, duration of the CAD and body mass index between the groups. Hypertension and diabetes mellitus type 2 were more frequent in the CAD patients than in the controls (p < 0.01). Family history of the CAD was more frequent in the AMI and the UAP group than in the controls (p < 0.05). Serum concentrations of VCAM-1 was similar in the patients with AMI (955.9 +/- 117.8 ng/mL), UAP (952.4 +/- 139.1 ng/mL) and SAP (931 +/- 169.8 ng/mL), and significantly higher in these groups compared with the controls (823.4 +/- 97.6; p < 0.05, p < 0.05 and p < 0.1 respectively). Serum concentration of ICAM-1 was similar in the patients with AMI (699.2 +/- 125.6 ng/mL), UAP (727.6 +/- 171.8 ng/mL) and SAP (697.5 +/- 165.6 ng/mL), and significantly higher in these groups compared with the controls (583.4 +/- 86.6; p < 0.1, p < 0.05 and p < 0.1 respectively). CONCLUSION: Increased concentrations of VCAM-1 and ICAM-1, as markers of inflammation, showed the importance of inflammatory processes in development of atherosclerosis and clinical expresion of CAD. Measurement of soluble ICAM-1 and VCAM-1 concentrations is a usefull indicator of atherosclerosis presence but not severity of CAD clinical presentation.

[Arthritis in paraneoplastic syndrome--a way to early cancer diagnosis? A case report]. / Artritis u sklopu paraneoplasticnog sindroma- -put do rane dijagnoze neoplazme? Prikaz bolesnika.

Paraneoplastic syndrome is defined by clinical, radiological, and biological features associated with malignant disease without direct tumor invasion. The aim of our study was to present clinical and laboratory features of six cases ofparaneoplastic arthritis, witch can help to establish early cancer diagnosis, and help to distinguish paraneoplastic arthritis from other rheumatic diseases. According to our case analysis, pareneoplastic arthritis has occurred in both sex equally, all patients were older than 45 years, in most of cases it occurred within 14 months before cancer diagnosis, usually in early stage of cancer. Clinical features of paraneoplastic arthritis were: symmetric poliarthritis, usually were affected small hand joints and knees, predominant acute onset, and rheumatic nodes weren't present. Laboratory tests showed: high inflammatory markers (C-reactive protein, and erythrocyte sedimentation level), negative rheumatoid factor, and negative anti-citrullinated protein antibody. X-ray scan did not show signs of joint destruction. Long term remission ofparaneoplastic arthritis was achieved by treatment of cancer.