Single Versus Maintenance Intravesical Chemotherapy for the Prevention of Bladder Recurrence after Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Randomized Clinical Trial

Harraz, Ahmed; Elshabrawy, Magdy; El-Nahas, Ahmed R.; El‐Kappany, Hamdy A.; Osman, Yasser

doi:10.1016/j.clgc.2019.07.019

Cited by 19 publications

(11 citation statements)

References 25 publications

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“…Clinically, bladder cancer patients are usually treated with the tumor resection, but even so, the recurrence rate is still very high ( Li et al., 2015 ). Intravesical instillation chemotherapy is needed to reduce the recurrence rate, but these chemotherapy drugs have serious complications, such as urinary pain, hematuria, allergy, and other toxic side effects ( Godwin et al., 2018 ; Harraz et al., 2019 ). Therefore, it is necessary to find a safe and effective drug to inhibit bladder cancer progression with less adverse effects.…”

Section: Introductionmentioning

confidence: 99%

Gallic Acid Inhibits Bladder Cancer T24 Cell Progression Through Mitochondrial Dysfunction and PI3K/Akt/NF-κB Signaling Suppression

Zeng

et al. 2020

Front. Pharmacol.

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Gallic acid (GA), a hydrolyzable tannin, has a wide range of pharmacological activities. This study revealed that, GA significantly inhibited T24 cells viability in a concentration-and time-dependent manner. The IC 50 of GA stimulating T24 cells for 24, 48, and 72 h were 21.73, 18.62, and 11.59 µg/ml respectively, and the inhibition rate was significantly higher than the positive control drug selected for CCK-8 assay. Meanwhile, after GA treatment, the morphology of T24 cells were changed significantly. Moreover, GA significantly inhibited T24 cells proliferation and blocked T24 cells cycle in S phase (p < 0.001). GA induced T24 cells apoptosis (p < 0.001), accompanied by reactive oxygen species (ROS) accumulation and mitochondrial membrane potential (MMP) depolarization. Western blotting analysis showed that GA significantly increased Cleaved caspase-3, Bax, P53, and Cytochrome C (Cyt-c) proteins expression, and decreased Bcl-2, P-PI3K, P-Akt, P-IkBa, P-IKKa, and P-NF-kB p65 proteins expression in T24 cells (p < 0.05). Real-Time PCR results verified that GA significantly promoted Caspase-3, Bax, P53, and Cyt-c genes expression, and inhibited Bcl-2, PI3K, Akt, and NF-kB p65 genes expression (p < 0.001). However, on the basis of GA (IC 50) stimulation, NAC (an oxidative stress inhibitor) pretreatment reversed the apoptotic rate of T24 cells and the expression of Bax, Cleaved caspase-3, P53, Bcl-2 proteins, and the MMP level in T24 cells, as well as the expression of Cyt-c protein in T24 cells mitochondria and cytoplasm. In addition, GA significantly suppressed T24 cells migration and invasion ability with VEGF protein inhibition (p < 0.001). Briefly, GA can inhibit T24 cells proliferation, metastasis and promote apoptosis, and the pro-apoptotic activity is closely associated with mitochondrial dysfunction and PI3K/Akt/NF-kB signaling suppression. Our study will help in finding a safe and effective treatment for bladder cancer.

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Section: Introductionmentioning

confidence: 99%

Gallic Acid Inhibits Bladder Cancer T24 Cell Progression Through Mitochondrial Dysfunction and PI3K/Akt/NF-κB Signaling Suppression

Zeng

et al. 2020

Front. Pharmacol.

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“…Some studies have found that positive urine cytology was an independent predictor for tumor recurrence [ 35 ], and the proximity of the site of bladder mucosal injury and intravesical recurrence locations confirmed the “tumor seeding” theory [ 36 ]. Multifocal tumors appear from dispersed viable cancer cells and are therefore monoclonal, transforming by either intraluminal seeding or intraepithelial migration, particularly during surgery [ 37 ]. In our study, of the 158 patients, 63 subsequently had bladder tumors after nephroureterectomy during follow-up, with an intravesical recurrence rate of 39.8%, which favors the theory of monoclonal origin by intraluminal seeding.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, Huang et al proposed that dispersed viable intraluminal cancer cells are not totally eliminated by a single instillation of chemotherapy, and multiple instillations were more efficient, which supported the theory of “field change” [ 38 ]. The whole urothelium is exposed to a variety of carcinogenic insults that can lead to malignancy and multifocal tumors, subsequently derived from separate clones of transformed cells [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Assessment of Therapeutic Benefit and Option Strategy on Intravesical Instillation for Preventing Bladder Cancer Recurrence after Radical Nephroureterectomy in Patients with Upper Urinary Tract Urothelial Carcinoma

Fan

Teng

Sun

et al. 2022

Journal of Oncology

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Objective. Upper urinary tract urothelial carcinoma (UUT-UC) is a very aggressive disease, characterized by 22%–50% of patients suffering from subsequent bladder recurrence after radical nephroureterectomy (RNU). Although the therapy of intravesical instillation is reported to be effective in preventing bladder recurrence, no study had been reported in Northeast China. The findings relating to the clinical effectiveness of intravesical instillation after RNU are somewhat controversial, and the best efficacy and least adverse effects of instillation drugs have not been widely accepted. Here, we aimed at evaluating the efficacy of intravesical instillation for the prevention intravesical recurrence systematically. Methods. In this retrospective cohort study, from October 2006 to September 2017, 158 UUT-UC patients underwent RNU were divided into 4 groups: epirubicin (EPB) instillation group, hydroxycamptothecin (HCPT) instillation group, bacillus Calmette–Guerin (BCG) instillation group, and noninstillation group. Cox univariate and multivariate analyses were employed to identify the risk factors for intravesical recurrence-free survival (IVRFS). The nomogram model was also applied to predict patient outcomes. Subsequently, to evaluate the clinical significance of intravesical instillation comprehensively, several databases including PubMed, Ovid, and Embase were searched and data from published studies with our results were combined by direct meta-analysis. Moreover, a network meta-analysis comparing instillation therapies was conducted to evaluate the clinical efficacy of different instillation drugs. Results. In our retrospective cohort study, the Kaplan–Meier survival curve demonstrated noninstillation groups were associated with worsened IVRFS. Meanwhile, multivariate analysis indicated that intravesical instillation was independent protective factors for IVRFS (hazard ratio [HR] = 0.731). Moreover, calibration plots, receiver operating characteristic (ROC) curves, area under the curve (AUC) values, and the C-index showed the priority of nomogram’s predictive accuracy. Next, direct meta-analysis including 19 studies showed that intravesical instillation could prevent the recurrence of bladder cancer with a pooled risk ratio (RR) estimate of 0.53. Subgroup analysis by study type, year of intravesical recurrence, first instillation time, and instillation times also confirmed the robustness of the results. Moreover, intraoperative instillation was associated with a decrease in the risk of bladder recurrence compared with postoperative instillation. Then, a network meta-analysis including 7 studies indicated that pirarubicin (THP) (surface under the cumulative ranking curve [SUCRA] = 89.2%) is the most effective therapy to reduce the risk of bladder recurrence, followed by BCG (SUCRA = 83.5%), mitomycin C (MMC) (SUCRA = 53.6%), EPB (SUCRA = 52.6%), and HCPT (SUCRA = 5.1%) after the analysis of the value ranking. Conclusions. A maintenance schedule of intravesical instillation prevents the recurrence of bladder cancer after RNU in UUT-UC patients effectively. Large, prospective trials are needed to further confirm its value. Compared with other chemotherapy regimens, THP may be a promising drug with favorable efficacy to prevent bladder recurrence. As included studies had moderate risk of bias, the results of network meta-analysis should be applied with caution.

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“…Bladder tumors are commonly treated by radical cystectomy coupled with cisplatin-based chemotherapy [ 2 , 3 ]. However, cisplatin occasionally generates adverse effects [ 4 , 5 ]. Therefore, it is critical to identify more antiproliferation agents for bladder cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

Antibladder Cancer Effects of Excavatolide C by Inducing Oxidative Stress, Apoptosis, and DNA Damage In Vitro

et al. 2022

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Excavatolide C (EXCC) is a bioactive compound derived from the gorgonian octocoral Briareum excavatum, and its anticancer effects are rarely addressed, particularly for bladder cancer. This investigation aimed to explore the potential impacts of EXCC on inhibiting the proliferation of three kinds of bladder cancer cells (5637, BFTC905, and T24). EXCC inhibits bladder cancer cell proliferation based on 48 h ATP assay. This antiproliferation function is validated to be oxidative stress dependent. Cellular and mitochondrial oxidative stresses were upregulated by EXCC, accompanied by depleting glutathione and mitochondrial membrane potential. These antiproliferation and oxidative stress events were suppressed by N-acetylcysteine (NAC), indicating that EXCC has an oxidative stress-regulating function for antiproliferation of bladder cancer cells. Oxidative stress-related responses such as apoptosis, caspase activation, and DNA damage were upregulated by EXCC and reverted by NAC. Taken together, the antiproliferation function of EXCC provides a potential treatment against bladder cancer cells via oxidative stress modulation.

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Single Versus Maintenance Intravesical Chemotherapy for the Prevention of Bladder Recurrence after Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Randomized Clinical Trial

Cited by 19 publications

References 25 publications

Gallic Acid Inhibits Bladder Cancer T24 Cell Progression Through Mitochondrial Dysfunction and PI3K/Akt/NF-κB Signaling Suppression

Gallic Acid Inhibits Bladder Cancer T24 Cell Progression Through Mitochondrial Dysfunction and PI3K/Akt/NF-κB Signaling Suppression

Assessment of Therapeutic Benefit and Option Strategy on Intravesical Instillation for Preventing Bladder Cancer Recurrence after Radical Nephroureterectomy in Patients with Upper Urinary Tract Urothelial Carcinoma

Antibladder Cancer Effects of Excavatolide C by Inducing Oxidative Stress, Apoptosis, and DNA Damage In Vitro

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