The aim of the present study was to evaluate the potential of Turkish propolis extracts if they prevent or protect foreskin fibroblast cells against hydrogen peroxide (H₂O₂)-induced oxidative DNA damage. Hydrogen peroxide (40 μM) was used as an inducer of oxidative DNA damage. The damage of DNA was evaluated by using the alkaline single cell gel electrophoresis (comet) assay. Turkish propolis extracts at concentrations of 25, 50, 75 and 100 μg/ml were prepared by ethanol. Anti-genotoxicity was assessed before, simultaneously, and after treatment of propolis extract (50 μg/ml) with H₂O₂. The results showed a significant decrease in H₂O₂-induced DNA damage in cultures treated with propolis extract. The antioxidant activity of phenolic components found in propolis may contribute to reduce the DNA damage induced by H₂O₂. Our findings confirmed the chemopreventive activity of propolis and showed that this effect may occur under different mechanisms.

Objective: This study was designed to compare the oxidative stress parameters of patients with polycythemia vera (PV) to those of healthy volunteers and to investigate the probable relationship between vascular events and parameters of oxidative status such as total oxidative status (TOS), total antioxidant status, oxidative stress index (OSI) and malondialdehyde (MDA) in PV patients. Material and Methods: Thirty-five PV patients (20 males and 15 females) and 20 healthy volunteers (11 males and 9 females) were enrolled. The oxidative status parameters of the patients were measured by spectrophotometric analyses at the time of diagnosis and at 6 months after treatment which consisted of phlebotomy and 100 mg/day acetyl salicylic acid with or without hydroxyurea for the high- and low-risk disease group, respectively. These parameters were compared both to healthy controls and to each other, in order to obtain the values before and after treatment. In addition, during diagnosis, the oxidative status parameters of patients with PV and a history of a vascular event were compared with those of patients with no history of a vascular event. Results: The TOS, OSI and MDA values were significantly higher in the patients than in the control group at the time of diagnosis. At 6 months after phlebotomy and 100 mg/day acetyl salicylic acid therapy, the TOS, OSI and MDA values were significantly lower in the patients when compared to the pretreatment values. The TOS and OSI levels were notably higher in the patients with a vascular-event history than in those without this history. Conclusion: Oxidative stress parameters were increased in PV patients.

No abstract

Survivin, β-catenin, and p53 are well-known cell-cycle and apoptosis regulators of tumorigenesis. Urothelial carcinomas (UCs) are the most common of the human cancers. Compared to superficial tumors (Ta, CIS, or T1), invasive UCs are important with regard to recurrence, progression, and mortality. Therefore, we examined whether survivin, β-catenin, and p53 could be used as the biomarkers for the early prediction of the invasiveness of UCs and the overall survival of the patients. We investigated the prognostic expressions of those biomarkers in UC (n=147) and in non-muscle invasive UC (NMI-UC) (n=113), using tissue microarray and immunohistochemistry. Spearman's correlation analysis and multivariate Cox regression analyses were used for statistical interpretation. High expressions of β-catenin, survivin, and p53 were associated with a high T stage, recurrence, progression, mortality, low recurrence-free survival, low progression-free survival and low overall survival (p <0.01). Similar findings were achieved for recurrence and progression in the NMI-UC group, except for mortality. Moreover, a positive correlation was shown between p53 and β-catenin and between p53 and survivin (r=0.221, p <0.01; r=0.236, p <0.01, respectively). Survivin, p53, and β-catenin overexpression, as prognostic markers, might suggest that the UCs are biologically aggressive with the poor prognosis. Thus, dysregulation of those these cell-cycle and apoptosis regulators in bladder carcinoma could be used as a molecular marker to determine the best treatment strategy and could contribute to the development of targeted therapies.

The renin-angiotensin system (RAS) is involved in cell growth, proliferation and differentiation in bone marrow in an autocrine-paracrine manner, and it modulates normal and neoplastic haematopoietic cell proliferation. This study aimed to assess expressions of the RAS components, renin, angiotensinogen and angiotensin-converting enzyme (ACE), during imatinib mesylate treatment of patients with chronic myeloid leukaemia (CML). Expressions of RAS components were studied in patients with CML at the time of diagnosis (n = 83) and at 3, 6 and 12 months after diagnosis (n = 35) by quantitative real-time polymerase chain reaction. De novo CML patients had increased ACE, angiotensinogen and renin mRNA levels and these expression levels decreased following administration of imatinib. The RAS activities were significantly different among Sokal risk groups of CML, highlighting the altered biological activity of RAS in neoplastic disorders. The results of this study confirm that haematopoietic RAS affects neoplastic cell production, which may be altered via administration of tyrosine kinase inhibitors such as imatinib mesylate.

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Local bone marrow renin-angiotensin system (RAS) is an autocrine-paracrine system affecting normal and neoplastic hematopoiesis. Angiotensin converting enzyme (ACE) converts angiotensinogen-I to its physiologically active peptide angiotensin-II, which stimulates proliferation and differentiation of hematopoietic stem cells through angiotensin II type 1 receptors. We investigated the ACE insertion/deletion (I/D) gene polymorphisms in patients with hematological malignancies including acute and chronic leukemia, myelodysplastic syndrome and multiple myeloma. Our results showed that 80.4% of the patients represented ID/II genotype, whereas it was 55.9% of the control group and 3.2 fold increased disease risk in the existence of insertion allele (ID/II). This is the first study demonstrating possible effects of ACE I/D gene polymorphism of the local bone marrow RAS components on leukemic hematopoiesis.

A AB BS ST TR RA AC CT T O Ob bj je ec ct ti iv ve e: : Polycythemia is known as increased erythrocytosis and is linked to the erythropoiesis cascade including erythropoietin, erythropoietin receptor and intracellular signaling proteins. The Janus kinase 2 (JAK2) is the key signal transducer in the erythropoiesis cascade. A function gain mutation (V617F) at JAK2 gene has been identified in polycythemia vera in adults. On the other hand, the molecular etiology of neonatal polycythemia has not been elucidated well. Thus, the aim of this randomized controlled study was to investigate the role of JAK2 V617F mutation in the etiology of neonatal polycythemia similar to polycythemia vera. M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : Fifty-one neonates diagnosed with polycythemia according to venous hematocrit level over 65% and 26 healthy neonates as the control group were enrolled in the study in addition to 43 adult patients diagnosed with polycythemia vera. JAK2 V617F mutation analysis was performed using Real-Time PCR system. R Re es su ul lt ts s: : All the neonatal polycythemia patients were negative for the specific mutation JAK2 V617F, as well as 26 control neonates, whereas in 31 (72%) out of 43 adult polycythemia vera patients, JAK2 V617F mutation was present. C Co on nc cl lu us si io on n: : This is the first report showing that JAK2-V617F mutation may be an acquired somatic mutation instead of congenital and neonatal polycythemia is not related to the disrupted erythropoiesis cascade.K Ke ey y W Wo or rd ds s: : Polycythemia; polycythemia vera; janus kinase 2; infant, newborn; mutation Ö ÖZ ZE ET T A Am ma aç ç: : Polisitemi artmış eritrositoz olarak bilinmektedir ve eritropoetin, eritropoetin reseptörü ve hücre içi sinyal proteinlerini kapsayan eritropoez zinciri ile bağlantılıdır. Janus kinaz 2 (JAK2), eritropoez zincirindeki anahtar sinyal iletim proteini olup, eritropoezin tek hücre içi kinaz proteinidir. Erişkinlerde görülen polisitemi vera hastalığının moleküler zemininde JAK2 geninde bir fonksiyon kazanım mutasyonu olan v617f tanımlanmıştır. Diğer taraftan, yenidoğan polisitemisinin moleküler etiyolojisi çok iyi aydınlatılamamıştır. Bu randomize kontrollü çalışmanın amacı, polisitemi verada olduğu gibi Janus Kinaz 2 (JAK2) V617F mutasyonunun yenidoğan polisitemisinin de etyolojisinde etken olup olmadığını araştırmaktır. G Ge er re eç ç v ve e Y Yö ön n--t te em ml le er r: : Venöz hematokrit düzeyi %65'in üzerinde olmasına göre polisitemi tanısı konulan 51 yenidoğan hasta ile kontrol grubu olarak 26 sağlıklı yenidoğan çocuk çalışılmıştır. Ek olarak, polisitemi vera tanısı almış 43 erişkin hasta çalışmaya dahil edilmiştir. JAK2 V617F mutasyon analizi gerçek zamanlı polimeraz zincir reaksiyonu yöntemi ile yapılmıştır. B Bu ul lg gu ul la ar r: : Yenidoğan polisitemisi olan 51 hasta, kontrol grubundaki 26 yenidoğana benzer şekilde, özgül JAK2 V617F mutasyonu açısından negatif bulundu. Ancak, 43 erişkin polisitemi vera hastasından 31 (%72)'inde JAK2 V617F mutasyonu tespit edildi. S So on ...