Vitamin C as a weapon against cancer

Since vitamin C (ascorbic acid) has been discovered over 80 years ago, it is known as a “miracle pill” because it possesses a lot of properties which are extremely essential for correct functioning of the organism. For a long time it has been also debated the usage of the ascorbic acid in prevention and cancer treatment. Literature reviewed in this paper provides many valuable information about mechanisms of anticancer effect of the vitamin C and about potential ability of ascorbic acid application in fight against cancer. That includes: parenteral administration of pharmacological doses of vitamin C, its beneficial influence on the final effect of chemo- and radiotherapy and its highly promising co-administration with other active compounds. Onkol. Prak. Klin. 2011; 7, 1: 9–23Odkąd ponad 80 lat temu odkryto witaminę C (kwas askorbinowy) i poznano jej niezwykle istotne dla prawidłowego funkcjonowania organizmu właściwości, zaczęto postrzegać ją jako „cudowną pigułkę”. Od dawna debatowano również na temat wykorzystania kwasu askorbinowego w prewencji i leczeniu raka. Zebrane i przedstawione w niniejszej pracy dane z piśmiennictwa dostarczają wielu cennych informacji na temat mechanizmów przeciwnowotworowego działania witaminy C oraz potencjalnych możliwości jej zastosowania w walce z nowotworem: począwszy od pozajelitowego podawania farmakologicznych dawek kwasu askorbinowego, przez jego korzystny wpływ na końcowy efekt chemio- i radioterapii, aż do bardzo obiecującego efektu podawania witaminy w połączeniu z innymi substancjami aktywnymi. Onkol. Prak. Klin. 2011; 7, 1: 9–2

Inflammatory response gene polymorphisms and their relationship with colorectal cancer risk

<p>Abstract</p> <p>Backgroud</p> <p>Patients with chronic inflammatory bowel disease (IBD) are at an increased risk of colorectal cancer (CRC) and it is estimated that one in six persons diagnosed with IBD will develop CRC. This fact suggests that genetic variations in inflammatory response genes may act as CRC disease risk modifiers.</p> <p>Methods</p> <p>In order to test this hypothesis we investigated a series of polymorphisms in 6 genes (NOD2, DLG5, OCTN1, OCTN2, IL4, TNFα) associated with the inflammatory response on a group of 607 consecutive newly diagnosed colorectal cancer patients and compared the results to controls (350 consecutive newborns and 607 age, sex and geographically matched controls).</p> <p>Results</p> <p>Of the six genes only one polymorphism in TNFα(-1031T/T) showed any tendency to be associated with disease risk (64.9% for controls and 71.4% for CRC) which we further characterized on a larger cohort of CRC patients and found a more profound relationship between the TNFα -1031T/T genotype and disease (64.5% for controls vs 74.7% for CRC cases above 70 yrs). Then, we investigated this result and identified a suggestive tendency, linking the TNFα -1031T/T genotype and a previously identified change in the CARD15/NOD2 gene (OR = 1.87; p = 0,02 for CRC cases above 60 yrs).</p> <p>Conclusion</p> <p>The association of polymorphisms in genes involved in the inflammatory response and CRC onset suggest that there are genetic changes capable of influencing disease risk in older persons.</p

N-acetyl-beta-glucosaminidase urine activity as a marker of early proximal tubule damage and a predictor of the long-term function of the transplanted kidneys

Introduction: Ischaemia-reperfusion injury (IRI) is a factor leading to the damages of the transplanted kidney, what affects mainly the proximal tubules. Early monitoring of tubule damage can be an efficient tool to predict the allograft dysfunction. Present in proximal tubules, N-acetyl-beta-glucosaminidase (NAG) is a lysosomal enzyme whose excretion rises as a result of IRI or acute rejection. The aim of this study was to monitor the NAG urine activity to evaluate the early proximal tubule damage, and to try to predict the long-term function of the transplanted kidney. Material and methods: The study enrolled 87 Caucasian renal transplant recipients (61.7% males, 38.3% females, mean age 45.56±14.34 years). Urine samples were collected for NAG and creatinine analysis on the 1st day after transplantation, and then in the 3rd and 12th month. Protocol biopsies were performed in the 3rd and 12th month. Results: A significant positive correlation between NAG urine activity in the 3rd month after transplantation and creatinine concentration on the 14th (p=0.004) and 30th day (p=0.05), in the 3rd month (p=0.009) and after the 1st (p=0.005) and 2nd year (p=0.003) was observed. A statistically significantly higher urinary NAG activity in samples collected in the first 3 days and in the 3rd month after transplantation among patients with DGF (p=0.006 and p=0.03 respectively) was found. There was a significant positive correlation between NAG urine activity in the 3rd month and the grade of tubular atrophy in specimens collected in the 3rd (p=0.03) and 12th (p=0.04) month. Conclusions: Monitoring of NAG urine activity is useful in the evaluation of early proximal tubule damage and predicting the long-term function of the transplanted kidneys. Key words: allograft, CAD, DGF, kidney function, NAG. INTRODUCTION According to the United Network for Organ Sharing (UNOS) records, 40% of renal allografts are lost during the first decade after transplantation N-acetyl-beta-glucosaminidase (NAG) is a lysosomal enzyme present in the proximal tubules of the kidney, normally secreted in small concentrations as a consequence of a natural exocytosis process (Price 1992). It was shown that after administration of cadmium, contrast agents, aminoglycosides and other nephrotoxic drugs, excretion of NAG increases * e-mail: [email protected] Abbreviations: CAN, chronic allograft nephropathy; CIT, cold ischaemia; GFR, glomerular filtration rate; HLA, human leukocyte antigen; IRI, Ischaemia-reperfusion injury; NAG, N-acetyl-beta-glucosaminidase; PRA, panel-reactive antibody; TA/IF, tubular atrophy and interstitial fibrosis Urine samples were collected for NAG and creatinine analysis on the 1st day after transplantation, and then in the 3rd and 12th month. Among subjects that did not produce urine because of delayed graft function (DGF), the first sample was collected when the amount of urine reached 500 ml per day, which was not later than on the 3rd day after the transplantation. These samples corresponded with the urine samples collected on the 1st day after transplantation from patients without DGF, and they were analysed together. The collected samples were centrifuged at 4000 rpm for 10 min, and urine without the sediment was stored at -80ºC until the time of analysis. The activity of NAG was measured by the Maruhn colorimetric method using p-nitrophenyl-N-acetyl-β-Dglucosamine (Sigma-Aldrich) as a substrate RESULTS The GFR and NAG activity during the study are presented in In regard to histopathological changes in renal allograft biopsies, there was a significant positive correlation between NAG urine activity in the 3rd month after transplantation and the grade of tubular atrophy in specimens collected in the 3rd (p=0.03) and 12th (p=0.04) month There was a significant positive correlation between NAG urine activity in the 3rd month after transplantation and the grade of proteinuria in single urine samples in the 3rd month after transplantation (p=0.05), and a significant positive correlation between NAG urine activity in the 12th month, and the grade of proteinuria in single urine samples in the 12th month after transplantation (p=0.01). Moreover, NAG urine activity in the 3rd month after transplantation correlated positively with the time of dialysis before transplantation (p=0.02), and negatively with the volume of residual diuresis (p=0.05). There was no correlation between urinary NAG activity and immunosuppressive agent concentrations. A higher NAG urine activity in the 3rd month after transplantation was observed in recipients of kidneys from donors with ischaemic or haemorrhagic stroke as a reason of death (p=0.03). DISCUSSIO

N-acetyl-beta-glucosaminidase urine activity as a marker of early proximal tubule damage and a predictor of the long-term function of the transplanted kidneys

Introduction: Ischaemia-reperfusion injury (IRI) is a factor leading to the damages of the transplanted kidney, what affects mainly the proximal tubules. Early monitoring of tubule damage can be an efficient tool to predict the allograft dysfunction. Present in proximal tubules, N-acetyl-beta-glucosaminidase (NAG) is a lysosomal enzyme whose excretion rises as a result of IRI or acute rejection. The aim of this study was to monitor the NAG urine activity to evaluate the early proximal tubule damage, and to try to predict the long-term function of the transplanted kidney. Material and methods: The study enrolled 87 Caucasian renal transplant recipients (61.7% males, 38.3% females, mean age 45.56±14.34 years). Urine samples were collected for NAG and creatinine analysis on the 1st day after transplantation, and then in the 3rd and 12th month. Protocol biopsies were performed in the 3rd and 12th month. Results: A significant positive correlation between NAG urine activity in the 3rd month after transplantation and creatinine concentration on the 14th (p=0.004) and 30th day (p=0.05), in the 3rd month (p=0.009) and after the 1st (p=0.005) and 2nd year (p=0.003) was observed. A statistically significantly higher urinary NAG activity in samples collected in the first 3 days and in the 3rd month after transplantation among patients with DGF (p=0.006 and p=0.03 respectively) was found. There was a significant positive correlation between NAG urine activity in the 3rd month and the grade of tubular atrophy in specimens collected in the 3rd (p=0.03) and 12th (p=0.04) month. Conclusions: Monitoring of NAG urine activity is useful in the evaluation of early proximal tubule damage and predicting the long-term function of the transplanted kidneys