The Limberg flap procedure is a good treatment choice for pilonidal sinus because of its low complication rate, the short time to return to normal activity, and good long-term results. This procedure has good postoperative results and is a comfortable surgical method for the patient.
Background: Urolithiasis is endemic in Turkey and characteristics of urolithiasis vary in different regions of the world. The aim of the present study was to evaluate the etiological and clinical characteristics and course of pediatric urolithiasis in south-east Turkey.
Methods:The study population consisted of 81 children (52 girls) with urolithiasis at a mean age of 6.2 ± 4.2 years who were followed up for 1-32 months.Results: Metabolic disorders, anatomical defects and infection stones were found to be the etiological factor in 34.6, 29.6 and 22.2% of patients, respectively, while 13.6% of patients were considered idiopathic. Of all patients, 28.4% were admitted with acute renal failure (ARF) and 72.8% had urinary tract infection. Recurrence was seen in 19.8% of patients at presentation. The localization of the stone was found to be in the upper urinary tract, the lower urinary tract or both in 65.4, 14.8% and 17.3% of patients, respectively. Patients with multiple and bilateral stones had a higher risk for ARF than the others. The risk for chronic renal failure was significantly higher in children with multiple, bilateral or recurrent stones and with ARF at presentation. Conclusions: Early diagnosis and management of renal stones and urinary tract infections is necessary to prevent the development of ARF or chronic renal failure and to improve the quality of a patient's life.
Ş Şspectrophotometry, high-performance liquid chromatography to detect serum levels of vitamins and MDA, and fluorometry to detect serum levels of selenium.
RESULTSThe serum levels of vitamin A, E and C, and selenium were significantly lower ( P < 0.05) in patients with TCC than in controls. However, erythrocyte GSH-Px activities ( P < 0.05) and serum MDA levels ( P < 0.01) were significantly higher in patients with TCC than in the controls.
CONCLUSIONSLevels of free oxygen species were higher, and antioxidant vitamin and selenium levels lower, in patients with bladder TCC than in controls. These findings, with the results of previous animal studies, suggest that giving vitamin A, C, E and selenium may be beneficial in preventing and treating human bladder cancer.
Background
Senescent cells accumulate in tissues over time as part of the natural ageing process and the removal of senescent cells has shown promise for alleviating many different age-related diseases in mice. Cancer is an age-associated disease and there are numerous mechanisms driving cellular senescence in cancer that can be detrimental to recovery. Thus, it would be beneficial to develop a senolytic that acts not only on ageing cells but also senescent cancer cells to prevent cancer recurrence or progression.
Methods
We used molecular modelling to develop a series of rationally designed peptides to mimic and target FOXO4 disrupting the FOXO4-TP53 interaction and releasing TP53 to induce apoptosis. We then tested these peptides as senolytic agents for the elimination of senescent cells both in cell culture and in vivo.
Findings
Here we show that these peptides can act as senolytics for eliminating senescent human cancer cells both in cell culture and in orthotopic mouse models. We then further characterized one peptide, ES2, showing that it disrupts FOXO4-TP53 foci, activates TP53 mediated apoptosis and preferentially binds FOXO4 compared to TP53. Next, we show that intratumoural delivery of ES2 plus a BRAF inhibitor results in a significant increase in apoptosis and a survival advantage in mouse models of melanoma. Finally, we show that repeated systemic delivery of ES2 to older mice results in reduced senescent cell numbers in the liver with minimal toxicity.
Interpretation
Taken together, our results reveal that peptides can be generated to specifically target and eliminate FOXO4+ senescent cancer cells, which has implications for eradicating residual disease and as a combination therapy for frontline treatment of cancer.
Funding
This work was supported by the Cancer Early Detection Advanced Research Center at Oregon Health & Science University.
Degradation of basement membranes underlying superficial carcinomas or CIS of the urothelium was significantly related to p53 inactivation, mdm2 overexpression, or both. The expression status of mdm2 should provide better information about the progression of superficial urothelial carcinomas than the status of p53 alone.
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