Purpose: Immune checkpoint inhibitors (ICIs) in general have shown poor efficacy in bladder cancer (BCa). The purpose of this project was to determine whether photodynamic therapy (PDT) with BCa-specific porphyrin-based PLZ4-nanoparticles (PNP) potentiated ICI. Experimental Design: SV40 T/Ras double-transgenic mice bearing spontaneous BCa and C57BL/6 mice carrying syngeneic bladder cancer models were used to determine the efficacy and conduct molecular correlative studies. Results: PDT with PNP generated reactive oxygen species, induced protein carbonylation and dendritic cell maturation. In SV40 T/Ras double-transgenic mice carrying spontaneous bladder cancer, the median survival was 33.7 days in the control, compared to 44.8 (p=0.0123), 52.6 (p=0.0054) and over 75 (p=0.0001) days in the anti-programmed cell death-1 antibody(anti-PD-1), PNP PDT and combination groups, respectively. At Day 75 when all mice in other groups died, only one in 7 mice in the combination group died. For the direct anti-tumor activity, compared to the control, the ani-PD-1, PNP PDT and combination groups induced a 40.25% (p=0.0003), 80.72% (p<0.0001) and 93.03% (p<0.0001) tumor reduction, respectively. For the abscopal anti-cancer immunity, the anti-PD-1, PNP PDT and combination groups induced tumor reduction of 45.73% (p=0.0001), 54.92% (p<0.0001) and 75.96% (p<0.0001), respectively. The combination treatment also diminished spontaneous and induced lung metastasis. Potential of immunotherapy by PNP PDT is multifactorial. Conclusions: In addition to its potential for photodynamic diagnosis and therapy, PNP PDT can synergize immunotherapy in treating locally advanced and metastatic bladder cancer. Clinical trials are warranted to determine the efficacy and toxicity of this combination.
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Objective: Increased pneumoperitoneum pressure during laparoscopic surgery can result in acute kidney injury. We aimed to clarify whether intraabdominal pressure tolerance is modified in various degrees of unilateral kidney hydronephrosis in rabbits. Methods: A total 90 rabbits were randomly allocated to three groups (group PN, PM and PS, i.e. rabbits with no, mild and severe hydronephrosis, respectively, subjected to intraabdominal pressures). Rabbits in group PM (n = 30) and group PS (n = 30) underwent a surgical procedure inducing a mild or severe left hydronephrosis. Rabbits in all groups were then allocated to 5 subgroups. Then, they were subjected to intraabdominal pressures of 0, 6, 9, 12, and 15 mm Hg, respectively. Acute kidney injury was assessed by measuring serum creatinine (Scr), blood urea nitrogen (BUN), tubular cell apoptosis, kidney injury molecule-1 (KIM-1) and cysteine-rich 61 (Cyr-61/CCN1) expression. Results: Acute kidney injury with increased tubular apoptosis and KIM-1 and Cyr-61 expression occurred when intraabdominal pressure reached 15, 15 and 9 mm Hg in PN, PM and PS groups, respectively. The Scr and BUN levels were similar in all groups. Conclusions: In rabbits, kidneys with severe hydronephrosis were more likely to suffer acute injury when they were exposed to pneumoperitoneal pressure.
ObjectiveWe aimed to study whether tolerance to irrigation pressure could be modified by evaluating the oxidative damage of obstructed kidneys based on rabbit models experiencing different degrees of hydronephrosis.MethodsA total of 66 rabbits were randomly divided into two experimental groups and a control group. In the experimental groups, the rabbits underwent a surgical procedure inducing mild (group M, n=24) or severe (group S, n=24) hydronephrosis. In each experimental group, the rabbits were then randomly divided into 4 subgroups (M0-M3 and S0-S3) consisting of 6 rabbits each. Group 0 received no perfusion. Groups 1 through 3 were perfused with 20, 60 and 100 mmHg fluid, respectively. For the control group, after a sham operation was performed, the rabbits were divided into 4 subgroups and were perfused with fluid at 0, 20, 60 or 100 mmHg of pressure. Kidney injuries was evaluated by neutrophil gelatinase associated lipocalin (NGAL). Oxidative damage was assessed by analyzing superoxide dismutase (Mn-SOD) activity, malondialdehyde (MDA) levels, glutathione reductase (GR), catalase (CAT) and peroxide (H2O2) levels, mitochondrial injuries was assessed by mitochondrial membrane potential (MMP), the mitochondrial ultrastructure and tubular cell apoptosis.ResultsIn the experimental groups, all results were similar for groups 0 and 1. In group 2, abnormalities were observed in the S group only, and the kidneys of rabbits in group 3 suffered oxidative damage and mitochondrial injuries with increased NGAL, decreased Mn-SOD, GR and CAT,increased MDA and H2O2, lower levels of MMP, mitochondrial vacuolization and an increased apoptotic index.ConclusionIn rabbits, severely obstructed kidneys were more susceptible to oxidative damage and mitochondrial injury than mildly obstructed kidneys when subjected to higher degrees of kidney perfusion pressure.
<b><i>Objective:</i></b> The aim was to summarize the experience of percutaneous holmium laser lithotripsy in the treatment of bladder calculi with lower urinary tract obstruction or pelvic joint disease in our hospital, explore its efficacy and safety, and improve the minimally invasive surgical technique for bladder calculi. <b><i>Methods:</i></b> The clinical data of 61 patients with bladder calculi combined with lower urinary tract obstructive diseases, including urethral stricture, benign prostatic hyperplasia, and bladder neck contracture or pelvic joint diseases in our hospital from 2017 to 2019 were retrospectively analyzed. All patients with bladder stones measuring 1.5–9 cm were placed in supine or lithotomy position. B-scan was conducted to locate the puncture above the pubic symphysis, establishing a 16–30 Fr bladder channel, and Lumenis holmium laser lithotripsy was subsequently performed through a Li Xun Nephroscope. The crushed stones were flushed out through the percutaneous bladder channel or taken out with foreign body forceps. After surgery, the cystostomy tube was indwelled for 3 days. <b><i>Results:</i></b> All the 61 cases were operated successfully with an average lithotripsy time of 25 min, and there was no conversion to open surgery. Postoperative reexamination showed neither residual calculi nor complications such as severe infection, massive hemorrhage, and intestinal injury. <b><i>Conclusion:</i></b> Percutaneous holmium laser lithotripsy is an improved minimally invasive surgical technique for the treatment of bladder calculi with the advantages of clear surgical field, high stone removal efficiency, less trauma, low-pressure bladder perfusion, and low incidence of accessory injury and infection. For patients with lower urinary tract obstructive disease resulting in obstruction of transurethral surgery and patients with pelvic joint disease resulting in difficult lithotomy position placement, this procedure is more advantageous than transurethral surgery. It is also suitable for bladder calculus with a long diameter >5 cm or multiple calculi.
Abstract. Quantum dots (QDs) are a type of fluorescent label with applications in biological molecules, cells and in vivo imaging. The current study investigated the effect of QDs on the toxicity, proliferation, migration and invasion of the EJ human bladder cancer cell line in vitro. The cell counting kit-8 test was used to measure the survival rate of EJ cells following incubation with varying concentrations of QDs. Additionally, the effect of QDs on tumor cell migration and invasion was evaluated using the Transwell chamber assay, and cell proliferation rate was assessed using a hemocytometer. Data from the current study demonstrated no significant differences in survival rate between the experimental and control groups with the conventionally used concentrations (5, 10 and 20 nM) of QD605 (P>0.05). However, with high concentrations of QD605 (40 and 80 nM), significant differences were observed (P<0.001). The survival rate of EJ cells, however, remained at 92.6%. In addition, no significant differences were observed between the EJ cells labeled with transactivator of transcription (TAT)-QD605 and the unlabeled EJ cells with regard to proliferation, migration and invasion (P>0.05). Thus, the results of the current study indicate that QDs exhibit a certain degree of influence on the activity of the EJ bladder cancer cell line at high concentrations. However, at the concentrations that QDs are conventionally used, there was little impact on the survival of the EJ cells. In addition, the proliferation, migration and invasion abilities of the EJ cells were not affected by TAT-QDs. Therefore, the peptide-conjugated QDs have potential to be applied in the imaging and tracking of live cells in vitro and of animals in vivo. Notably, QDs may provide the foundation for a novel, non-invasive imaging strategy for the early diagnosis of tumors.
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