A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldPreviously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.info:eu-repo/grantAgreement/EC/FP7/21807

Role of Nanoparticles in the Treatment of Noninvasive Bladder Cancer

WOS: 000219415200013Bladder cancer is the ninth most common cancer types in the world and transitional bladder cancer constitutes 90% of all bladder cancer neoplasms depending on cancer cell morphology. Clinical choice of treatment is transurethral resection (TUR), after which the recurrence rate is 50-80% and the tumor has a 14% chance of progression. To avoid recurrence and progression, adjuvant intravesical chemotherapy or immunotherapy is required. Intravesical drug delivery has many advantages. Bladder allows manipulation since it is easily accessible and a closed area, allows catheterization rendering this organ to be an advantageous site for localized drug delivery. Drugs are administered into urinary bladder directly resulting in greater exposure of tissues to drug. On the other hand, because of periodical discharge, rapid drug dilution necessitates repeated catheterization and results in loss of drug efficacy. Another disadvantage is the very low permeability of urothelium. Urothelium limits the absorption of molecules into the systemic circulation and prevent adherence of foreign agents on the urothelial surface exerting the same effect of drugs and drug delivery systems. To overcome these problems, nanotechnological approach in the biomedical field seems promising and in this frame new drug carrier systems were focused and bioadhesive nanoparticles were developed. Nanoparticles are submicron, solid, colloidal particles in a size ranging between 10 to 1000 nm. Nanoparticles are generally prepared from biodegradable polymers with specific physicochemical properties and are loaded with active molecules to act as drug delivery systems. Bioadhesive nanoparticles allow prolonged residence time of drug in the mucosal tissues such as bladder wall and can be promising to pass the bladder permeability barrier. Due to their particle size and surface charge, they sustain the drug release at cancerous tissues and protect the drug from acidic urine pH and other degradation factors such as hydrolysis and photodegradation. In addition, nanoparticulate carriers form a drug reservoir in the action site to reduce drug loss and to improve drug efficacy. In this study, we aim to review the role and application of nanoparticles in noninvasive bladder tumors with current literature

Garlic supplemented diet attenuates gentamicin nephrotoxicity in rats

Purpose: To demonstrate the effect of a 4% pulverized garlic supplemented diet on the nephrotoxicity induced by gentamicin in rats. Materials and Methods: Twenty four healthy male Wistar rats, weighing between 220 - 260grams, were divided into three groups. The rats were randomly assigned to either the gentamicin injection without garlic supplementation group (Group I, n = 8), gentamicin injection with garlic supplementation group (Group II, n = 8), and control group (Group III, n = 8). Urine from the rats was collected and the volume (mL), microalbumin (mg/L), creatinine (mg/dL), Na (mmol/L), K (mmol/L), Cl (mmol/L), P (mg/dL), N-acetyl glucosamine (NAG) (U/L) and pH values were measured. Then urea (mg/dL), creatinine (mg/dL), total protein (g/dL) and cystatin (mg/L) values were measured for the blood samples obtained from tail veins. Results: The median NAG value for the control group (52.050 U/L) was similar to value for Group II (56.400 U/L), which received gentamicin and the garlic diet. However, the median NAG value for Group I (77.030 U/L), which received gentamicin without garlic supplementation, was determined to be statistically significantly higher (p = 0.010) than the value for the control group. In addition, the mean cystatin value for Group II (1.360 U/L) was found to be statistically significantly lower than the value for the Group I (2.240 U/L) (p = 0.015). Conclusions: In this study we showed the effect of 4% pulverized garlic supplemented diet for preventing nephrotoxicity induced by gentamicin in rats by using as parameters NAG in urine samples and cystatin C in serum samples

Garlic supplemented diet attenuates gentamicin nephrotoxicity ın rats

Purpose To demonstrate the effect of a 4% pulverized garlic supplemented diet on the nephrotoxicity induced by gentamicin in rats. Materials and Methods Twenty four healthy male Wistar rats, weighing between 220 - 260grams, were divided into three groups. The rats were randomly assigned to either the gentamicin injection without garlic supplementation group (Group I, n = 8), gentamicin injection with garlic supplementation group (Group II, n = 8), and control group (Group III, n = 8). Urine from the rats was collected and the volume (mL), microalbumin (mg/L), creatinine (mg/dL), Na (mmol/L), K (mmol/L), Cl (mmol/L), P (mg/dL), N-acetyl glucosamine (NAG) (U/L) and pH values were measured. Then urea (mg/dL), creatinine (mg/dL), total protein (g/dL) and cystatin (mg/L) values were measured for the blood samples obtained from tail veins. Results The median NAG value for the control group (52.050 U/L) was similar to value for Group II (56.400 U/L), which received gentamicin and the garlic diet. However, the median NAG value for Group I (77.030 U/L), which received gentamicin without garlic supplementation, was determined to be statistically significantly higher (p = 0.010) than the value for the control group. In addition, the mean cystatin value for Group II (1.360 U/L) was found to be statistically significantly lower than the value for the Group I (2.240 U/L) (p = 0.015). Conclusions In this study we showed the effect of 4% pulverized garlic supplemented diet for preventing nephrotoxicity induced by gentamicin in rats by using as parameters NAG in urine samples and cystatin C in serum samples

Prolonged retention and in vivo evaluation of cationic nanoparticles loaded with Mitomycin C designed for intravesical chemotherapy of bladder tumours

WOS: 000307999000008PubMed: 22468630To overcome the recurrence problem in bladder tumours; nanoparticles with positive surface charge may improve interaction with biological membranes for intravesical administration. The aim of this study was to design, develop and evaluate (in vitro-in vivo) cationic nanoparticles based on chitosan, poly-L-lysine or polycaprolactone for the effective intravesical delivery of chemotherapeutic agent MMC in a rat model. Poly-L-lysine-coated polycaprolactone nanoparticles and chitosan-coated polycaprolactone nanoparticles were prepared by the double emulsion technique. Chitosan nanoparticles were prepared by ionic gelation. It was found that nanoparticle formulations of 160-320nm in size can be produced in 14-35% encapsulation efficiency. Variability in the particle size of nanoparticles depended on the preparation method. Encapsulation was increased by two-fold for CS-PCL as a result of the double emulsion technique. Commercial MMC product in solution form and cationic nanoparticle formulations were compared for in vivo bladder retention properties and effect of formulations on urine volume.TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [109S172]; Turkish Academy of SciencesTurkish Academy of Sciences [EA-TUBA-GEBIP/2001-2-11]Authors would like to acknowledge that this project was financially supported by TUBITAK (Scientific Research Project Number: 109S172). Alper B. Iskit has been supported by the Turkish Academy of Sciences, in the framework of the Young Scientist Award Program (EA-TUBA-GEBIP/2001-2-11)

Values for free/total prostate-specific antigen ratio as a function of age: necessity of reference validation in a Turkish population

WOS: 000248542900019PubMed: 17617037Background: The aim of this study was to evaluate age-related changes in free/total prostate-specific antigen (f/t PSA) ratio, focusing on the avoidance of unnecessary prostate biopsies. Methods: A total of 898 men aged 30-88 years without a history of prostate surgery and disease were enrolled into the study. Serum tPSA, fPSA and f/t PSA ratios were determined for the study population and for different age categories. All males who had suspicious digital rectal examination and tPSA > 4 ng/mL underwent transrectal ultrasonography-guided prostate biopsy. Receiver operating characteristic (ROC) curves for each group were generated by plotting the sensitivity vs. 1-specificity for the f/t PSA ratio. The sensitivity and specificity were obtained using different f/t PSA ratio cutoffs for different age groups. Results: Prostate cancer was detected in 63 patients (7%). Age-specific cutoffs were determined according to likelihood ratios at the levels of 10%, 15% and 15% f/t PSA ratio for ages 50-59, 60-69 and >= 70 years, respectively. However, a single cutoff of 10% is recommended across all age ranges (positive likelihood ratio 2.36). ROC curves demonstrated that the area under the curve (AUC) was significant for all patients with initial PSA of 4-10 ng/mL (AUC 0.703-0.796), except for the >= 70-year age group (AUC 0.549). Conclusions: The current study showed that the use of f/t PSA ratio in patients with PSA levels of 4-10 ng/mL should enhance the specificity of PSA screening and decrease the number of unnecessary biopsies. f/t PSA levels may show dissimilarities according to age and ethnicity, so further studies are warranted to identify this relationship

Values for free/total prostate-specific antigen ratio as a function of age: necessity of reference validation in a Turkish population

Background: The aim of this study was to evaluate age-related changes in free/total prostate-specific antigen (f/t PSA) ratio, focusing on the avoidance of unnecessary prostate biopsies. Methods: A total of 898 men aged 30–88 years without a history of prostate surgery and disease were enrolled into the study. Serum tPSA, fPSA and f/t PSA ratios were determined for the study population and for different age categories. All males who had suspicious digital rectal examination and tPSA >4 ng/mL underwent transrectal ultrasonography-guided prostate biopsy. Receiver operating characteristic (ROC) curves for each group were generated by plotting the sensitivity vs. 1–specificity for the f/t PSA ratio. The sensitivity and specificity were obtained using different f/t PSA ratio cutoffs for different age groups. Results: Prostate cancer was detected in 63 patients (7%). Age-specific cutoffs were determined according to likelihood ratios at the levels of 10%, 15% and 15% f/t PSA ratio for ages 50–59, 60–69 and ≥70 years, respectively. However, a single cutoff of 10% is recommended across all age ranges (positive likelihood ratio 2.36). ROC curves demonstrated that the area under the curve (AUC) was significant for all patients with initial PSA of 4–10 ng/mL (AUC 0.703–0.796), except for the ≥70-year age group (AUC 0.549). Conclusions: The current study showed that the use of f/t PSA ratio in patients with PSA levels of 4–10 ng/mL should enhance the specificity of PSA screening and decrease the number of unnecessary biopsies. f/t PSA levels may show dissimilarities according to age and ethnicity, so further studies are warranted to identify this relationship

The Evaluation of Efficacy and Safety of Holmium: YAG Lithotripsy for Treatment of Ureteric Stones

Holmium YAG laser is an excellent intracorporeal lithotripsy device for all kinds of stones. The aim of this study was to evalute the efficacy and safety of Holmiyum laser for treatment of uretenic stone

Intravesical cationic nanoparticles of chitosan and polycaprolactone for the delivery of Mitomycin C to bladder tumors

Cationic nanoparticles of chitosan (CS), poly-epsilon-caprolactone coated with chitosan (CS-PCL) and poly-e-caprolactone coated with poly-L-lysine (PLL-PCL) were developed to encapsulate intravesical chemotherapeutic agent Mitomycin C (MMC) for longer residence time, higher local drug concentration and prevention of drug loss during bladder discharge. Nanoparticle diameters varied between 180 and 340 nm depending on polymer used for preparation and coating. Zeta potential values demonstrated positive charge expected from cationic nanoparticles. MMC encapsulation efficiency depended on hydrophilicity of polymers since MMC is water-soluble. Encapsulation was increased by 2-fold for CS-PCL and 3-fold for PLL-PCL as a consequence of hydrophilic coating. Complete drug release was obtained with only CS-PCL nanoparticles. On the other hand, CS and PLL-PCL nanoparticles did not completely liberate MMC due to strong polymer-drug interactions which were elucidated with DSC studies. As far as cellular interaction was concerned, CS-PCL was the most efficient formulation for uptake of fluorescent markers Nile Red and Rhodamine123 incorporated into nanoparticles. Especially, CS-PCL nanoparticles loaded with Rhodamine123 sharing hydrophilic properties with MMC were selectively incorporated by bladder cancer cell line, but not by normal bladder epithelial cells. CS-PCL nanoparticles seem to be promising for MMC delivery with respect to anticancer efficacy tested against MB49 bladder carcinoma cell line. (C) 2008 Elsevier B.V. All rights reserved