Recommended oral sodium bicarbonate administration for urine alkalinization did not affect the concentration of mitomycin-C in non-muscle invasive bladder cancer patients.

Objective: Sodium bicarbonate has been reported to maximize the efficacy of intravesical instillation of mitomycin-C (IVI-MMC) therapy by urine alkalinization in non-muscle-invasive bladder cancer (NMIBC). This study aimed to analyze the changes in MMC concentration according to urinary pH and evaluate the efficacy of sodium bicarbonate to maintain the concentration of active form of MMC during IVI-MMC.

Methods: We prospectively enrolled 26 patients with NMIBC after transurethral resection of bladder tumor.

Polypyrrole-based nanotheranostics for activatable fluorescence imaging and chemo/photothermal dual therapy of triple-negative breast cancer.

Here, we fabricated polypyrrole nanoparticles (PPys) (termed HA10-PPy, HA20-PPy, and HA40-PPy) doped with different average molecular weight hyaluronic acids (HAs) (10, 20, and 40 kDa, respectively), and evaluated the effect of molecular weight of doped HA on photothermal induction, fluorescence quenching, and drug loading efficiencies. Doxorubicin-loaded HA-doped PPys (DOX@HA-PPys) could be used for imaging and therapy of triple-negative breast cancer (TNBC). Fluorescence turn-on, stimuli-responsive drug release, and photo-induced heating of DOX@HA-PPys enabled not only activatable fluorescence imaging but also subsequent chemo/photothermal dual therapy for TNBC.

Antitumor activity of the c-Myc inhibitor KSI-3716 in gemcitabine-resistant bladder cancer.

Intravesical instillation of chemotherapeutic agents is a well-established treatment strategy to decrease recurrence following transurethral resection in non-muscle invasive bladder cancer. Gemcitabine is a recently developed treatment option. However, the curative effects of gemcitabine are far from satisfactory due to de novo or acquired drug resistance.

Intravesical instillation of c-MYC inhibitor KSI-3716 suppresses orthotopic bladder tumor growth.

Purpose: c-MYC is a promising target for cancer therapy but its use is restricted by unwanted, devastating side effects. We explored whether intravesical instillation of the c-MYC inhibitor KSI-3716 could suppress tumor growth in murine orthotopic bladder xenografts.

Materials And Methods: The small molecule KSI-3716, which blocks c-MYC/MAX binding to target gene promoters, was used as an intravesical chemotherapy agent.

Small-molecule inhibitors of c-Myc transcriptional factor suppress proliferation and induce apoptosis of promyelocytic leukemia cell via cell cycle arrest.

c-Myc plays a decisive role in the proliferation of HL-60 promyelocytic leukemia cells. In the present study, we demonstrated that an inhibitor of c-Myc/Max/DNA complex formation has a high potentiality as a suppressor of c-Myc-involved cell signaling. We prepared recombinant c-Myc and Max proteins encompassing the human-origin DNA binding and dimerization domains, and tested a chemical library of 6480 small molecules for their inhibitory effect on the in vitro formation of the c-Myc/Max/DNA complex as well as their influence on DMSO-differentiated HL-60 cells.

The mechanism of transglutaminase 2 inhibition with glucosamine: implications of a possible anti-inflammatory effect through transglutaminase inhibition.

Purpose: Although many efforts on revealing mechanism of the constitutive activation of NF-κB in cancer cells contributed to understanding canonical pathways, largely it remains to be determined for therapeutic approaches. Recently, we found that increased expression of transglutaminase 2 (TGase 2) appears to be responsible for constitutive activation of NF-κB in certain types of cancer cells. In previous studies, we demonstrated that TGase 2 inhibition markedly increases anti-cancer drug sensitivity in drug resistance cancer cells.

Expression of ammonia transporters, Rhbg and Rhcg, in chronic cyclosporine nephropathy in rats.

Background/aims: Cyclosporine (CsA)-induced renal injury causes renal tubular acidosis. The current study was performed to evaluate the influence of CsA-induced renal injury on the ammonia transporter family members, Rh B-glycoprotein (Rhbg) and Rh C-glycoprotein (Rhcg).

Methods: Rats were treated daily for 1 or 4 weeks with vehicle (VH) or CsA.

Infiltration of nestin-expressing cells in interstitial fibrosis in chronic cyclosporine nephropathy.

Background: Nestin-expressing cells play a role in the repair process of injured tissues and organs. This study examined the nestin-expressing cells in interstitial fibrosis in experimental chronic cyclosporine A (CsA) nephropathy.

Methods: Sprague Dawley rats were treated daily for 1 or 4 weeks with CsA (15 mg/kg) or vehicle (VH; olive oil, 1 mg/kg).

Prolonged endoplasmic reticulum stress induces apoptotic cell death in an experimental model of chronic cyclosporine nephropathy.

Background/aims: Apoptosis contributes to cyclosporine (CsA)-induced renal cell death. This study tested the effects of CsA-induced endoplasmic reticulum (ER) stress on apoptotic cell death in an experimental model of chronic CsA nephropathy.

Methods: CsA (15 mg/kg per day) was given to rats for 7 or 28 days.

Activation of intrarenal complement system in mouse model for chronic cyclosporine nephrotoxicity.

Purpose: Local activation of the complement system plays a role in target organ damage. The aim of our study was to investigate the influence of cyclosporine (CsA)- induced renal injury on the complement system in the kidney.

Materials And Methods: Mice fed a low salt (0.

Renoprotective effects of rosiglitazone in stroke-prone spontaneously hypertensive rats.

Background/aims: Rosiglitazone (RGTZ) has a protective effect against various types of injury. We evaluated the effects of RGTZ on renal injury in a stroke-prone spontaneously hypertensive rat (SHRSP) model.

Methods: Male SHRSP rats were observed with or without RGTZ treatment for 10 weeks.

Induction of PPAR gamma mRNA and protein expression by rosiglitazone in chronic cyclosporine nephropathy in the rat.

Purpose: We recently reported that rosiglitazone (RGTZ), a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, has a protective effect against cyclosporine (CsA)- induced renal injury. Here we report the effect of RGTZ on peroxisome proliferator-activated receptor gamma (PPARgamma) expression in an experimental model of chronic cyclosporine (CsA) nephropathy.

Materials And Methods: Chronic CsA nephropathy was induced in Sprague-Dawley rats by administering CsA (15mg/kg per day) for 28 days, and control rats were treated with vehicle (VH group, olive oil 1mL/kg per day) for 28 days.

Influence of angiotensin II on expression of toll-like receptor 2 and maturation of dendritic cells in chronic cyclosporine nephropathy.

Background: Angiotensin (Ang) II plays an important role in immune regulation. We evaluate the influence of the renin-angiotensin system (RAS) in the innate immune response caused by cyclosporine A (CsA)-induced renal injury.

Methods: Two separate studies were performed in Sprague Dawley rats.

Downregulation of renal sodium transporters and tonicity-responsive enhancer binding protein by long-term treatment with cyclosporin A.

Tonicity-responsive enhancer binding protein (TonEBP) is a transcriptional activator that is regulated by ambient tonicity. TonEBP protects the renal medulla from the deleterious effects of hyperosmolality and regulates the urinary concentration by stimulating aquaporin-2 and urea transporters. The therapeutic use of cyclosporin A (CsA) is limited by nephrotoxicity that is manifested by reduced GFR, fibrosis, and tubular defects, including reduced urinary concentration.

Effect of FTY720 on chronic cyclosporine nephropathy in rats.

Background: Long-term treatment with cyclosporine A (CsA) causes tubulointerstitial inflammation and fibrosis in the kidney. To define the role of lymphocytes in this process, the novel lymphocyte-specific inhibitor FTY720 was administered to rats with experimental model of chronic CsA nephropathy.

Methods: Sprague-Dawley rats were treated daily for 4 weeks with CsA (7.

Cyclosporine-induced renal injury induces toll-like receptor and maturation of dendritic cells.

Background: The toll-like receptor (TLR) is stimulated by not only pathogen-associated molecular patterns but also endogenous TLR ligands provided by injured cells. The influence of cyclosporine A (CsA)-induced renal injury on TLR expression and subsequent signaling pathway was evaluated.

Methods: Induction of chronic CsA nephropathy was made by administering CsA (15 mg/kg/day) for 28 days in rats.

Protective effect of peroxisome proliferator activated receptor gamma agonists on diabetic and non-diabetic renal diseases.

Peroxisome proliferator activated receptor gamma (PPARgamma) agonist has not only antidiabetic effect but also a protective effect against various types of injury of the kidney. The protective effects of PPARgamma agonists are observed in diabetic nephropathy and non-diabetic renal diseases such as 5/6 ablation model of renal failure, experimental glomerulonephritis, ischemia-reperfusion injury, hypertensive nephropathy and cyclosporin-induced renal injury. The mechanism of renoprotection by PPARgamma agonist is multifactorial.

Rosiglitazone protects against cyclosporine-induced pancreatic and renal injury in rats.

Rosiglitazone (RGTZ) has protective effect against various types of injury. This study was performed to evaluate the effect of RGTZ on pancreatic and renal injury caused by cyclosporine (CsA). CsA (15 mg/kg) and RGTZ (3 mg/kg) were administered alone and together to the rats for 28 days.

Ischemia-reperfusion injury activates innate immunity in rat kidneys.

Background: There is growing evidence of a role of the immune system in the pathophysiology of ischemia-reperfusion (I/R) injury, but the influence of I/R injury on innate immunity is still undetermined.

Methods: Sprague-Dawley rats were used. I/R injury was induced by clamping both renal arteries for 45 min, and the rats were killed 1, 3, 5, and 7 days later.

Attenuation of interstitial inflammation and fibrosis by recombinant human erythropoietin in chronic cyclosporine nephropathy.

Background: Evidence suggests that recombinant human erythropoietin (rHuEPO) protects neurons and cardiomyocytes from acute insults. We investigated the protective effect of rHuEPO on cyclosporine (CsA)-induced renal injury.

Methods: CsA (15 mg/kg/day) was given to rats for 1 or 4 weeks, and rHuEPO was concurrently administered at a dose of 100 units/kg (thrice weekly).