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ABSTRACT: Taxanes have high activity against breast cancer cells either as the single agent or in combination with other anticancer compounds. The aim of the study was to determine the effects of vitamin A compounds on the cytotoxic action of paclitaxel and on the expression of ERs in the MCF-7 breast cancer cells. Retinol and beta-carotene, but not retinoids, added to the culture exerted an effect on paclitaxel activity. However, only beta-carotene significantly reduced the percentage of proliferating cells (40.36% +/- 5.64, p < 0.01). We observed that vitamin A and its derivatives combined with paclitaxel and estradiol decreased the percentage of proliferating cells, but only in comparison to estradiol group, whereas retinol and lycopene administered together with paclitaxel and tamoxifen decrease significantly the percentage of proliferatin cells (36.85% +/- 4.71, p < 0.0001 and 37.22% +/- 1.59, p < 0.0001 respectively, compared with paclitaxel group). We have shown that paclitaxel increases the expression of ERalpha and ERbeta mRNA in MCF-7 line. The strongest effect of transcription inhibition ERalpha (2.5 times) and especially ERbeta (10 times) was observed after addition of 9-cis retinoic acid and paclitaxel. This data suggests a synergistic effect of the compounds on ERbeta down-regulation. Our results support the use of retinoid is treatment of ER positive breast cancer patients.
Gynecological Endocrinology 03/2009; 25(5):287-93. · 1.58 Impact Factor
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ABSTRACT: Renal osteodystrophy is a common complication of chronic renal failure and renal replacement therapy. The purpose of the study was to assess whether hemodialysis (HD) or hemodiafiltration (HDF) affects bone turnover. In all, 45 HD and 17 HDF patients were evaluated with respect to bone metabolism markers. We assessed PTH; markers of bone formation-alkaline phosphatase and its bone isoform, osteocalcin; markers of bone resorption- PICP, ICTP; Ctx; beta2-microglobulin; and urinary DPD. BMD were determined for femoral neck and lumbar spine (L2-L4) using DEXA. Hemodialyzed patients had lower calcidiol, calcitriol, and BMD in the femur neck, and higher phosphate, Kt/V, residual renal function, venous pH, osteocalcin, ALP, bALP, DPD, beta2-microglobulin, ICTP, Ctx, osteoprotegerin, and RANKL than patients on HDF. HDF seems to ameliorate bone metabolism in comparison with HD. Bone turnover in end-stage renal failure might be affected to some extent by the choice of renal replacement therapy.
Renal Failure 02/2007; 29(5):595-601. · 0.82 Impact Factor
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ABSTRACT: Development in diagnostic and therapeutic methods has led to increased survival rates in children with malignancies. The treatment with corticosteroids, methotrexate and irradiation may all cause reduction in bone mass. We assessed bone mineral density (BMD) and several parameters involved in bone formation in long-term survivors with a malignancy at completion of therapy. Total body and lumbar spine bone mineral densities (gram per cm2) were measured by dual energy x-ray absorptiometry in 40 patients (age 12-27 yr; median 17.5 yr; 21 with acute lymphoblastic leukemias, 19 with other malignancies) from 3 to 13.9 years (median 7 yr) after discontinuation of therapy. These results were compared with those from 473 healthy controls and expressed as a percentage of the age and sex-matched control values (mean and standard deviation). Serum levels of osteocalcin, bone specific alkaline phosphatase, parathormone, 1.25 dihydroxyvitamin D, urinary concentrations of deoxypyridinoline were determined as well as several specific markers of bone turnover. RESULTS: The total BMD and in the lumbar spine were not significantly reduced in survivors of childhood malignancies compared to the control population. No correlation was found between the BMD values and the cumulative doses and time of corticosteroids, administered Mtx, irradiation, duration of treatment, age at diagnosis. Duration of follow-up showed correlation with lumbar spine BMD. Serum markers of bone formation and resorption were in the normal range (expressed as standard deviation score relative to the age and sex-matched healthy population), bone turnover was not disturbed at the time of the study. CONCLUSION: We found no difference in bone mineralisation between our patients and the healthy population.
Medycyna wieku rozwojowego 8(4 Pt 2):1041-54.
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ABSTRACT: Adiponectin may be used for assessing the risk of coronary artery disease (CAD) and may be related to the development of acute coronary syndrome. Decreased adiponectin has been associated with some risk factors for cardiovascular diseases such as male sex, obesity and diabetes mellitus. Adiponectin has antiatherogenic properties and attenuates endothelial inflammatory responses. CD146, a novel cell adhesion molecule, is localized at the endothelial junction. In kidney allograft recipients, endothelial dysfunction and atherosclerosis are almost universal. The aim of this cross-sectional study was to evaluate possible relations between adiponectin, CD146, and other markers of endothelial cell injury in 82 stable kidney transplant recipients (mean age 45 years, mean time after transplantation 47 months) with and without CAD.
Adiponectin and markers of endothelial injury: CD146, von Willebrand factor, thrombomodulin, ICAM, CD40L, P-selectin and other hemostatic markers were assessed using commercially available kits.
Patients with CAD had evidence of more pronounced endothelial dysfunction, procoagulant state and lower adiponectin than patients without CAD. Adiponectin correlated significantly, in univariate analysis, with CD146 (r = 0.29, p = 0.009), thrombomodulin (r = 0.37, p = 0.001), protein Z (r = -0.25, p = 0.03), BMI (r = -0.26, p = 0.047), serum creatinine (r = 0.26, p = 0.02) and urea (r = 0.38, p = 0.001). CD146 correlated significantly with von Willebrand factor (r = 0.33, p = 0.002), thrombomodulin (r = 0.25, p = 0.025), age (r = 0.34, p = 0.001), platelets (r = -0.33, p = 0.002), serum urea (r = 0.24, p = 0.039), cholesterol (r = 0.24, p = 0.046), ICAM (r = 0.23, p = 0.036), protein C activity (r = -0.26, p = 0.019) and tended to correlate with serum creatinine and time after transplantation. In multivariate linear regression, independent predictors of adiponectin were CD146, thrombomodulin and urea, and of CD146 was mainly age of patients.
Endothelial dysfunction and procoagulant state are more pronounced in kidney transplant recipients with CAD, particularly in those with lower GFR. In kidney transplant recipients, markers of endothelial cell injury are significantly increased relative to healthy volunteers. Elevation of adiponectin may be a defense mechanism against endothelial damage, reflected by elevated CD146 and thrombomodulin.
American Journal of Nephrology 25(3):203-10. · 2.54 Impact Factor
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ABSTRACT: Leptin plays an important role in the metabolism of adipose tissue. Considering that malignancy and its treatment cans affect normal development in childhood. We analysed the correlations between serum leptin levels and body composition after anticancer treatment. We studied 33 survivors (24 boys and 9 girls) who before our study, have been treated for acute lymphoblastic leukaemia (ALL) (n=23) and Hodgkin disease (n=10) after 7.15+/-3.5 years. Sixteen patients with ALL received cranial irradiation (12Gy). We measured body mass index (BM1) fat mass (FM) and lean body mass (LBM) using dual energy x-ray absorptiometry (DXA). We compared these results to the results obtained from reference values (SD score). Leptin levels were measured with the RIA method. RESULTS: 1. Mean leptin levels were higher in girls after puberty (10.93 ng/mL+/-8.9) than in boys (3.73 ng/mL+/-3. 7). In boys no differences were found in leptin levels between T2-4 and T5 stages. In girls the leptin values increased after puberty. Leptin SD score levels were higher in boys during (1.55 +/-1.0) and after puberty (1.46+/-0.75) and in girls - after puberty (1.19 +/-1.51). We did not find any influence of cranial irradiation (12Gy) or various methotrexate doses (5 g/m(2) vs. 19/m(2)) leptin values. 2. No difference in BMI SD score was found within the whole study group. 3. FM did not change ill boys during and after puberty, although FM SD score were higher during puberty (2.98 +/-4.8). In girls FM and FM SD score were higher after puberty. In boys and girls LBM augmented with pubertal development but LBM SD score in boys were lower after puberty (-1.67 +/-1.7) in comparison to puberty (0.2 +/-1.7). No differences were found between LBM SD score in girls during and after puberty. 4. We found a correlation between leptin levels and BMI (r=0.59 p=0.001) and FM (r=0.77 p=0.0001). 5. Relation of FM to LBM in boys remained unchanged, however in girls it increased within pubertal development. CONCLUSION: l. Anticancer treatment during childhood shows no influence on body mass index although the tendency to higher fat mass in pubertal boys and in post pubertal girls is observed. 2. Leptin values depend on fat mass and do not relate directly to the pubertal stage.
Medycyna wieku rozwojowego 8(2 Pt 1):297-307.
