Fabrication of magnetic niosomal platform for delivery of resveratrol: potential anticancer activity against human pancreatic cancer Capan-1 cell.

Recently, the presence of different nanoparticles (NPs) has developed targeting drug delivery in treatment of cancer cell. Targeted drug delivery systems using NPs have shown great promise in improving the efficacy of intracellular uptake as well as local concentration of therapeutics with minimizing side effects. The current study planned to synthesized resveratrol-loaded magnetic niosomes nanoparticles (RSV-MNIONPs) and evaluate their cytotoxicity activity in pancreatic cancer cells. For this aim, magnetic nanoparticles (MNPs) were synthesized and loaded into niosomes (NIOs) by the thin film hydration technique and then characterized via DLS, FT-IR, TEM, SEM and VSM techniques. Moreover, the cytotoxic activity of the RSV-MNIONPs on the Capan-1 cells line was assessed by the MTT test. The distribution number of RSV-MNIONPs was gained about 80 nm and 95 nm with surface charge of - 14.0 mV by SEM and TEM analysis, respectively. RSV loading efficacy in NIOs was about 85%, and the drug releases pattern displayed a sustained discharge with a maximum amount about 35% and 40%, within 4 h in pH = 7.4 and pH = 5.8, respectively. The cytotoxicity of the RSV-MNIONPs in the presence of an external magnetic field is higher than that of the RSV, indicating enhanced cellular uptake in their encapsulated states. Furthermore, RSV loaded MNNPs were found to induce more cell cycle arrest at the G0/G1 checkpoint than free RSV. Compared with RSV-treated cells, the mRNA expression levels of BAX, Bcl2, FAS, P 53, Cyclin D and hTERT, were significantly changed in cells treated with RSV loaded MNNPs. The niosomes NPs approaches have been widely used to attain higher solubility, improved bioavailability, enhanced stability, and control delivery of RSV. Our formulation displayed antitumor activity and can be considered an appropriate carrier with a great potential for future usage in cancer therapy.

FOXO1, a tiny protein with intricate interactions: Promising therapeutic candidate in lung cancer.

Nowadays, lung cancer is the most common cause of cancer-related deaths in both men and women globally. Despite the development of extremely efficient targeted agents, lung cancer progression and drug resistance remain serious clinical issues. Increasing knowledge of the molecular mechanisms underlying progression and drug resistance will enable the development of novel therapeutic methods. It has been revealed that transcription factors (TF) dysregulation, which results in considerable expression modifications of genes, is a generally prevalent phenomenon regarding human malignancies. The forkhead box O1 (FOXO1), a member of the forkhead transcription factor family with crucial roles in cell fate decisions, is suggested to play a pivotal role as a tumor suppressor in a variety of malignancies, especially in lung cancer. FOXO1 is involved in diverse cellular processes and also has clinical significance consisting of cell cycle arrest, apoptosis, DNA repair, oxidative stress, cancer prevention, treatment, and chemo/radioresistance. Based on the critical role of FOXO1, this transcription factor appears to be an appropriate target for future drug discovery in lung cancers. This review focused on the signaling pathways, and molecular mechanisms involved in FOXO1 regulation in lung cancer. We also discuss pharmacological compounds that are currently being administered for lung cancer treatment by affecting FOXO1 and also point out the essential role of FOXO1 in drug resistance. Future preclinical research should assess combination drug strategies to stimulate FOXO1 and its upstream regulators as potential strategies to treat resistant or advanced lung cancers.

Targeting long noncoding RNAs in neuroblastoma: Progress and prospects.

Neuroblastoma (NB) is the third most prevalent tumor that mostly influences infants and young children. Although different treatments have been developed for the treatment of NB, high-risk patients have been reported to have low survival rates. Currently, long noncoding RNAs (lncRNAs) have shown an attractive potential in cancer research and a party of investigations have been performed to understand mechanisms underlying tumor development through lncRNA dysregulation. Researchers have just newly initiated to exhibit the involvement of lncRNAs in NB pathogenesis. In this review article, we tried to clarify the point we stand with respect to the involvement of lncRNAs in NB. Moreover, implications for the pathologic roles of lncRNAs in the development of NB have been discussed. It seems that some of these lncRNAs have promising potential to be applied as biomarkers for NB prognosis and treatment.

Role of m6A modification in dysregulation of Wnt/ß-catenin pathway in cancer.

N6-methyladenosine (m6A) modification is the most abundant post-transcriptional regulation of RNAs in eukaryotes. Dysregulation of m6A readers, writers, and erasers can significantly promote tumorigenesis by altering the expression of various genes. Wnt/ß-catenin is an evolutionarily conserved signaling pathway that has recently been linked to the pathogenesis of many cancers. Given the significance of this pathway in regulating normal tissue homeostasis and stem cell differentiation, a subtle understanding of the molecular mechanism underlying its dysregulation is required for effective targeting. There is mounting evidence that m6A regulators are highly implicated in the dysregulation of the Wnt/ß-catenin signaling pathway. Since m6A regulators can affect Wnt pathway components and dysregulation of either leads to carcinogenesis, this study aims to clarify the relationship between m6A regulators and the Wnt/ß-catenin signaling pathway to investigate their combined impact on tumorigenesis.

Renal capsule for augmentation cystoplasty in canine model: a favorable biomaterial?

PURPOSE: To evaluate effectiveness of canine renal capsule for augmentation cystoplasty. MATERIALS AND METHODS: Ten adult dogs participated in this study. After induction of anesthesia each animal underwent bed side urodynamic study, bladder capacity and bladder pressure was recorded. Then via mid line incision abdominal cavity was entered, right kidney was identified and its capsule was dissected. Bladder augmentation was done by anastomosing the renal capsule to the bladder. After 6 months bed side urodynamic study was performed again and changes in bladder volume and pressure were recorded. Then the animals were sacrificed and the augmented bladders were sent for histopathology evaluation. RESULTS: Mean maximum anatomic bladder capacity before cystoplasty was 334.00±11.40cc which increased to 488.00±14.83cc post-operatively (p=0.039). Mean anatomic bladder pressure before cystoplasty was 19.00±1.58cmH2O which decreased to 12.60±1.14cmH2O post-operatively (p=0.039). Histopathology evaluation revealed epithelialization of the renal capsule with urothelium without evidence of fibrosis, collagen deposits or contracture. CONCLUSIONS: Our data shows that renal capsule is a favorable biomaterial for bladder augmentation in a canine model.

Renal capsule for augmentation cystoplasty in canine model: a favorable biomaterial?

ABSTRACT Purpose: To evaluate effectiveness of canine renal capsule for augmentation cystoplasty. Materials and Methods: Ten adult dogs participated in this study. After induction of anesthesia each animal underwent bed side urodynamic study, bladder capacity and bladder pressure was recorded. Then via mid line incision abdominal cavity was entered, right kidney was identified and its capsule was dissected. Bladder augmentation was done by anastomosing the renal capsule to the bladder. After 6 months bed side urodynamic study was performed again and changes in bladder volume and pressure were recorded. Then the animals were sacrificed and the augmented bladders were sent for histopathology evaluation. Results: Mean maximum anatomic bladder capacity before cystoplasty was 334.00±11.40cc which increased to 488.00±14.83cc post-operatively (p=0.039). Mean anatomic bladder pressure before cystoplasty was 19.00±1.58cmH2O which decreased to 12.60±1.14cmH2O post-operatively (p=0.039). Histopathology evaluation revealed epithelialization of the renal capsule with urothelium without evidence of fibrosis, collagen deposits or contracture. Conclusions: Our data shows that renal capsule is a favorable biomaterial for bladder augmentation in a canine model.

Which patients are at higher risk for residual valves after posterior urethral valve ablation?

PURPOSE: To find patients at high risk of obstructive remnant leaflets after valve ablation among boys with posterior urethral valve (PUV), we evaluated any possible relationship between preoperative findings in our patients and residual obstructive leaflets after valve ablation. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 55 patients with PUV that was treated by the same surgeon between 2008 and 2012. Of these, 37 patients (67.3%) had no obstructive remnant leaflets (group A) and 18 patients (32.7%) had obstructive remnant leaflets (group B) in follow-up cystoscopy. Preoperative clinical and radiological findings were evaluated and compared between the groups. RESULTS: AMONG ALL THE PREOPERATIVE DATA WE EXAMINED, THE ANALYSIS REVEALED THAT AGE AT THE TIME OF SURGERY (MEDIAN AGE: group A, 15 months; group B, 7 months; p=0.017), echogenicity of kidneys (p<0.05), presence of vesicoureteral reflux (p<0.05), and grade of reflux (p<0.05) were significantly different between the groups. Method of valve ablation, anterior-posterior diameters of the renal pelvis, renal cortical thickness, bladder wall thickening, and scarring on the dimercaptosuccinic acid scan showed no significant differences between the two groups. CONCLUSIONS: In our patients, younger age at surgery time, hyperechogenicity of renal parenchyma, presence of vesicoureteral reflux, and grade 4 or 5 reflux before surgery had a significant relationship with residual valves. More studies may result in enhanced management of patients at high risk of residual valves after PUV ablation, because the sooner the obstruction is resolved entirely, the better the outcome.

Result of endoureterotomy in the management of primary obstructive megaureter in the first year of life: preliminary report.

PURPOSE: The present study aimed to investigate the efficacy of endoureterotomy in patients who were less than 1-year-old with primary obstructive megaureter (POMU). PATIENTS AND METHODS: Three of 10 patients with POMU aged between 2 and 12 months for whom conservative management was not applicable had recurrent urinary tract infection (UTI) and urosepsis, while the rest had decreased renal function. After obtaining the clinical history and performing physical examinations and imaging studies (ultrasonography, voiding cystourethrography (VCUG), radionuclide renal scan), the patients underwent endoureterotomy using a neonatal ureteroscope (4.5F) and Bugbee electrode with pure cutting current at the 6 o'clock position. A Double-J stent was inserted and removed 1 week later. This was followed by serial physical examination, renal function test, urine analysis, urine culture, and imaging studies in the 1st month and every 3 months after Double-J stent removal. RESULTS: Hydroureteronephrosis was significantly decreased in nine patients. Postoperative VCUG revealed no sign of iatrogenic vesicoureteral reflux. In addition, a follow-up renal scan showed remarkable improvement in the renal function in the patients who had decreased renal function, except for one patient in whom uncontrolled urosepsis developed in the follow-up; the patient underwent cutaneous ureterostomy. No UTI was detected in the group who presented with recurrent UTI and urosepsis. CONCLUSION: According to the results of our study, endoureterotomy may be an alternative in management of POMU. Of course, further studies with longer follow-up periods are needed to confirm the applicability of this method in patients younger than 1 year.