p62 is associated with 2 major cellular defense mechanisms against metabolic and oxidative stress, autophagy and the Kelch-like ECH-associated protein 1 (KEAP1)nuclear factor-E2-related factor 2 (NRF2) system. Recent studies indicate that the p62-KEAP1-NRF2 pathway promotes tumorigenesis and tumor growth mediated by NRF2-dependent antioxidative response. However, whether p62 is involved in bladder cancer (BCa) development remains unknown. Here, we found that p62 is overexpressed in BCa tissue and several BCa cell lines. The knockdown of p62 inhibits BCa cell growth both in vitro and in vivo, with increased intracellular reactive oxygen species level. Mechanically, p62 activates NRF2 signaling by sequestrating KEAP1, which leads to the upregulation of antioxidant genes (Gclc, Gstm5, and Gpx2), thus protecting BCa cells from oxidative stress. Our findings indicate that p62 might be involved in the development of BCa and serve as a potential therapeutic target. K E Y W O R D S bladder cancer, KEAP1, NRF2, oxidative stress, p62 | 1157 LI et aL.
The present study aimed to examine the effects and mechanisms of exogenous C-X-C motif chemokine 5 (CXCL5) and lentiviral CXCL5 overexpression on the regulation of malignant behaviors of prostate cancer cells in vitro and in a nude mouse xenograft model. The expression levels of CXCL5 and a number of tumor-related genes were assessed by using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), western blotting, ELISA, or immunohistochemistry in normal and cancerous prostate cells and tissues. Cell proliferation, colony formation, and Transwell assays were performed to determine the effects of exogenous, autocrine, and paracrine CXCL5 on prostate cancer cell proliferative and migratory capacity. The results indicated that CXCL5 expression was upregulated in PC‑3 and DU145 prostate cancer cells, in WPMY‑1 normal prostate stromal cells, and in RWPE‑1 prostate epithelial cells, as well as in prostate cancer tissue specimens. Exogenous CXCL5 exposure resulted in increase in prostate cancer cell proliferation, colony formation, and migration. In cells transfected with a CXCL5 overexpression vector, in cells cultured in conditioned medium from CXCL5-overexpressing WPMY cells, and in cells co-cultured with CXCL5‑OE WPMY cells prostate cancer cell malignant phenotypes were induced in an autocrine/paracrine fashion in vitro; similar results were observed in nude mouse xenografts. CXCL5 overexpression also regulated expression of tumor-related genes, including BAX, N-Myc downstream-regulated gene 3, extracellular signal-regulated kinase 1/2, C-X-C chemokine receptor type 2, interleukin 18, Bcl‑2, and caspase‑3. These data demonstrated that CXCL5 expression was upregulated in prostate cancer tissues and that exogenous CXCL5 protein exposure or CXCL5 overexpression promoted malignant phenotypes of prostate cancer cells in vitro and in vivo.
Objective: Our study aimed to detect whether 450 nm blue laser can be applied effectively and safely in endosocopic submucosal dissection (ESD) system for surgery in colonic tissue. Background data: Semiconductor blue laser has been applied in surgery due to its excellent cutting property, however, whether blue laser can be applied in colonic surgery has not been reported. Materials and methods: Porcine colon tissues were vaporized by 450 nm blue semiconductor laser at 10-25 W and at working distances from 0.5 to 3 mm, with a three-dimensional scanning system. Moreover, we designed an ESD model and applied blue laser at 10 W on porcine colonic tissues with this system. Dimensions of the vaporized tissues and coagulation zones were assessed under microscopy. Results: Since the thickness of colonic wall is no more than 1 mm, first we determined the cutting property and safety of blue laser on porcine colon tissue and found that blue laser at 10 W made lesions shallower than 1 mm and the depth of vaporization can be controlled effectively within muscularis mucosa and submucosa. Moreover, a large scale of porcine colonic tissue was vaporized precisely by blue laser at power of 10 W with the ESD system ex vivo. Conclusions: Our results indicate that 450 nm blue laser at 10 W can be well controlled for laser-tissue interaction with excellent cutting efficiency and less thermal damage in adjacent tissues especially side of the submucosa. Therefore, 450 nm semiconductor blue laser could be a safe alternative approach for colonic surgery.
ObjectivesTo be the first to apply a novel 450 nm blue diode laser in transurethral resection of bladder tumor (TURBt) to treat patients with non-muscle invasive bladder cancer (NMIBC) and evaluate its efficacy and safety during the preoperative period compared to the conventional plasmakinetic electrocautery.Materials and MethodsRandomized controlled trial (RCT) in five medical centers was designed as a non-inferiority study and conducted from October 2018 to December 2019. Patients with NMIBC were randomized to the blue laser or plasmakinetic electrocautery group for TURBt. As the first study to evaluate this novel blue laser device, the primary outcome was the effective resection rate of bladder tumors, including effective dissection and hemostasis. The secondary outcomes were the perioperative records, including surgical time, postoperative indwelling catheter time, hospital stay length, blood loss, reoperation rate, wound healing and adverse events.ResultsA total of 174 patients were randomized to either the blue laser group (85 patients) or plasmakinetic electrocautery group (89 patients). There was no statistical significance in the clinical features of bladder tumors, including tumor site, number and maximum lesion size. Both the blue laser and plasmakinetic electrocautery could effectively dissect all visible bladder tumors. The surgical time for patients in the blue laser group was longer (p=0.001), but their blood loss was less than that of patients in the control group (p=0.003). There were no differences in the postoperative indwelling catheter time, hospital stay length, reoperation rate or other adverse events. However, the patients undergoing TURBt with the blue laser showed a faster wound healing at 3 months after operation.ConclusionThe novel blue laser could be effectively and safely used for TURBt in patients with NMIBC, and this method was not inferior to plasmakinetic electrocautery during the perioperative period. However, TURBt with the blue laser may provide the benefit to reduce preoperative blood loss and accelerate postoperative wound healing. Moreover, longer follow-up to confirm recurrence-free survival benefit was required.
BackgroundDiabetes mellitus‐induced erectile dysfunction is difficult to treat. The oxidative stress created by diabetes mellitus is a major cause of injuries to the corpus cavernosum, thereby resulting in erectile dysfunction. Near‐infrared laser has already been shown to be effective in treating multiple brain disorders because of its antioxidative stress effect.ObjectivesTo investigate whether a near‐infrared laser improves the erectile function of diabetes mellitus‐induced erectile dysfunction rats through its antioxidative stress effect.Materials and methodsKnowing its advantage of reasonable deep tissue penetration and good photoactivation on mitochondria, a near‐infrared laser with wavelength of 808 nm was used in the experiment. Since the internal and external corpus cavernosum were covered by different tissue layers, the laser penetration rates of the internal and external corpus cavernosum were measured separately. Different radiant exposure settings were applied: in the initial experiment, 40 male Sprague–Dawley rats were randomly assigned to five groups, normal controls, and streptozotocin‐induced diabetes mellitus rats that 10 weeks later received various radiant exposures (J/cm2) from the near‐infrared laser (DM0J(DM+NIR 0 J/cm2), DM1J, DM2J, and DM4J) in the subsequent 2 weeks. Erectile function was then assessed 1 week after near‐infrared treatment. It was found that the initial radiant exposure setting was not optimal according to the Arndt–Schulz rule. We performed a second experiment using a different radiant exposure setting. Forty male rats were randomly divided into five groups (normal controls, DM0J, DM4J, DM8J, and DM16J), and the near‐infrared laser was again applied according to the new setting, and erectile function was assessed as in the first experiment. Histologic, biochemical, and proteomic analyses were then conducted.ResultsRecovery of erectile function of varying degrees was observed in the near‐infrared treatment groups, and radiant exposure of 4 J/cm2 achieved optimal results. The DM4J group showed improvement in mitochondrial function and morphology in diabetes mellitus rats, and it was found that oxidative stress levels were significantly reduced by near‐infrared exposure. The tissue structure of the corpus cavernosum was also improved by near‐infrared exposure. The proteomics analysis confirming multiple biologic processes were changed by diabetes mellitus and near‐infrared.Discussion and conclusionNear‐infrared laser activated mitochondria, improved oxidative stress, repaired the damage to penile corpus cavernosum tissue structures caused by diabetes mellitus, and improved erectile function in diabetes mellitus rats. These results thus raise the possibility that human patients with diabetes mellitus‐induced erectile dysfunction may respond to near‐infrared therapy in a manner that parallels the responses we observed in animal study.
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