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BACKGROUND: Bladder cancer stem cells could promote the recurrence and drug resistance of bladder cancer. Numerous studies have shown that keratin 6B (KRT6B) is involved in the production and progression of tumors, and is closely related to the prognosis of tumors. OBJECTIVE: To observe the expression of keratin 6B in CD44+ bladder cancer stem cells and to show the influence of keratin 6B on proliferation, migration, and self-renewal of bladder cancer stem cells, and to further explore the effect of keratin 6B expression on the prognosis of bladder cancer patients. METHODS: (1) CD44+ 5637 bladder cancer stem cells were isolated by magnetic active cell sorting. Cancer stem cell-related gene expression of SOX2, OCT4, and NANOG was detected via real-time polymerase chain reaction. The spheroid formation assay was used to detect the ability of self-renewal of cancer stem cells in CD44+ cells. Keratin 6B expression was detected in CD44+ bladder cancer stem cells by real-time polymerase chain reaction. (2) The CD44+5637 bladder cancer stem cells were divided into two groups. In the keratin 6B siRNA group, keratin 6B small interfering RNA was transfected into CD44+ bladder cancer stem cells. Untransfected CD44+ bladder cancer stem cells were used as the black control group. Cells were collected at 2 days post-transfection. The proliferation, migration, and self-renewal capacity of keratin 6B siRNA CD44+ bladder cancer stem cells were detected by the colony and wound healing assay and spheroid formation respectively. (3) Totally 24 bladder cancer tissues were used by immunohistochemistry to analyze the expression of CD44v6 and keratin 6B. (4) ONCOMINE database was used to analyze the effect of keratin 6B expression on the overall survival of bladder cancer. RESULTS AND CONCLUSION: (1) Cancer stem cell-related genes (SOX2, OCT4, NANOG) and keratin 6B expression was higher in CD44+ cells isolated by magnetic active cell sorting compared with CD44- cells (P < 0.05). Cell proliferation, migration, and in vitro spheroid formation were significantly increased (P < 0.05). Keratin 6B small interfering RNA down-regulated the expression of keratin 6B in CD44+ bladder cancer stem cells (P < 0.05). (2) Compared with the blank control group, the proliferation and migration of CD44+ bladder cancer stem cells after transfection of keratin 6B small interfering RNA (P < 0.05), and the number of tumorsphere significantly diminished (P < 0.05); the expression of Notch1 and Hes1 mRNA increased (P < 0.05). (3) Keratin 6B and CD44v6 were significantly different in bladder cancer tissue (P=0.006). The overall survival rate of bladder cancer patients with high expression of keratin 6B was lower than that of patients with low expression of keratin 6B. (4) The results showed that keratin 6B was highly expressed in CD44+ bladder cancer stem cells, and could promote the proliferation, migration, and self-renewal capacity of bladder cancer stem cells. The high expression of keratin 6B contributes to improving the survival of bladder cancer patients.
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OBJECTIVE@#To explore the influences of andrographolide (Andro) on bladder cancer cell lines and a tumor xenograft mouse model bearing 5637 cells.@*METHODS@#For in vitro experiments, T24 cells were stimulated with Andro (0-40 µmol/L) and 5637 cells were stimulated with Andro (0 to 80 µmol/L). Cell growth, migration, and infiltration were assessed using cell counting kit-8, colony formation, wound healing, and transwell assays. Apoptosis rate was examined using flow cytometry. In in vivo study, the antitumor effect of Andro (10 mg/kg) was evaluated by 5637 tumor-bearing mice, and levels of nuclear factor κ B (NF- κ B) and phosphoinositide 3-kinase/AKT related-proteins were determined by immunoblotting.@*RESULTS@#Andro suppressed growth, migration, and infiltraion of bladder cancer cells (P⩽0.05 or P⩽0.01). Additionally, Andro induced intrinsic mitochondria-dependent apoptosis in bladder cancer cell lines. Furthermore, Andro inhibited bladder cancer growth in mice (P⩽0.01). The expression of p65, p-AKT were suppressed by Andro treatment in vitro and in vivo (P⩽0.05 or P⩽0.01).@*CONCLUSIONS@#Andrographolide inhibits proliferation and promotes apoptosis in bladder cancer cells by interfering with NF- κ B and PI3K/AKT signaling in vitro and in vivo.
Subject(s)
Animals , Apoptosis , Cell Line, Tumor , Cell Proliferation , Diterpenes/therapeutic use , Humans , Mice , NF-kappa B/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Urinary Bladder Neoplasms/drug therapyABSTRACT
In this study, we aimed to develop foods with antitumor and complementary effects against cisplatin (CDDP)-resistant bladder cancer. UMUC3, a human bladder cancer cell line was exposed to CDDP and cultured over a prolonged period to prepare UMUC3-CR, a CDDP-resistant subline. Androgen receptor mRNA expression was high in the UMUC3-CR subline. Genistein and vitamin C suppressed UMUC3-CR tumor growth. Additionally, the liberal intake of cheese in parental cell UMUC3-transplanted mice was associated with prolonged survival. Therefore, we created konjac jelly (KIK300) containing soy milk, cheese, and vitamin C as the main ingredients. Liberal administration of KIK300 to UMUC3-CR-transplanted mice suppressed tumor growth and reduced vascular endothelial growth factor mRNA expression. Furthermore, we observed no weight loss in the animals, their skin condition improved, and exercise capacity was improved. In conclusion, this study suggests that KIK300 may show antitumor and complementary effects on CDDP-resistant bladder cancer.
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Objective:This study aims to construct a prognostic model of bladder cancer (BLCA) based on lncRNA.Methods:BLCA lncRNA expression data and clinical information were downloaded from TCGA. Univariate Cox regression was used to evaluate the correlation between the expression level of each lncRNA and overall survival (OS), and the lncRNAs with a corrected P-value<0.01 were selected as candidate predictors. In the training queue, the prediction model is constructed by methods such as least absolute shrinkage and selection operator, and multi-factor stepwise Cox regression, and verified in the verification queue at the same time.. Evaluation the area under the curve of time-dependent receiver operating characteristic (tROC) and Harrel C index. According to the median risk score of the prediction model, patients were divided into high-risk group and low-risk group and the differences in clinicopathological characteristics between the two groups were compared by t-test or chi-square test. Results:Establish a BLCA prognostic model based on 13 lncRNAs, of which LINC01465, ARHGAP5-AS1, ZFHX4-AS1, MAFG-AS1 are prognostic risk factors (β regression coefficients are 0.32, 0.16, 0.06, 0.20, respectively, all>0), and the rest are protection factors (β regression coefficients are all<0); the prediction model of the overall survival in the first year, the third year, and the fifth year in the complete cohort has an area under the tROC curve of 0.79, 0.82, and 0.80 respectively, and the Harrell C index is 0.74. Its predictive ability is better than the previously published BLCA prognostic model based on lncRNA. Adjusting for confounding factors including age and tumor stage found that the risk score of this model was an independent poor prognostic factor for overall survival in BLCA patients (hazard ratio 4.05; P<0.001). Comparison of clinicopathological characteristics of patients in the high-risk and low-risk groups showed that in the high-risk group, there were more old patints (70.0 vs. 66.1, P<0.001), more non-papillary patients (74.2% vs. 61.2, P=0.005), more high-stage patients (37.6% vs. 28.0%, P<0.001 for stage Ⅳ patients), and more high-grade tumors (98.0% vs. 92.0%, P=0.005). Conclusion:In this study, a prognostic model of bladder cancer based on 13 lncRNAs was constructed. This model has good predictive ability and can provide value for clinical decision-making and patient consultation.
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Neoadjuvant therapy leads to the eradication of micrometastasis, thereby providing survival benefit to patients with muscle-invasive bladder cancer (MIBC). In the recent years, multiple clinical trials have corroborated the safety and durability of immune checkpoint inhibitors in the treatment of MIBC. Notably, there is a significantly higher response rate (e.g. pathologic complete response) and comparable occurrence of adverse events in patients treated with neoadjuvant dual immunotherapy, immunotherapy combined with chemotherapy or targeted therapy as compared with that treated with neoadjuvant single-agent immunotherapy. With an overview of breakthroughs in the past years, we believe that immune combination therapy is of great promise and expected to revolutionize the landscape of neoadjuvant therapy of MIBC.
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In 2022, ASCO genitourinary cancer symposium reported the latest progress in the diagnosis and treatment of urothelial carcinoma. Perioperative treatment progress include prediction of the effect of neoadjuvant chemotherapy for muscle invasive bladder cancer (MIBC) and upper urinary tract epithelial carcinoma (UTUC). The matched cohort study of bladder-sparing treatment showed that the effect of trimodality therapy (TMT) and radical cystectomy was equivalent in oncologic outcome. Immunotherapy showed promising effects in the circumstance of advanced urothelial carcinoma, neoadjuvant therapy and non muscle invasive bladder cancer (NMIBC) treatment. Poly-adenosine diphosphate ribose polymerase (PARP) inhibitors and antibody coupled drugs (ADC) show antitumor activity in the treatment of advanced urothelial carcinoma. The meeting also reported a series of progress in biomarkers related to the prediction of curative effect of urothelial carcinoma.
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Frailty is the clinical syndrome that occurs due to an increase in personal vulnerability and a decline in the ability to maintain one′s internal balance, which is closely related to the development of bladder cancer in the elderly. The research on frailty of elderly patients with bladder cancer in China is still in its infancy. This article discussed the risks of bladder cancer and frailty, the necessity of preoperative frailty assessment in patients with bladder cancer, commonly used assessment tools, and summarized the limitations of the existing evaluation tools to provide reference for further developing and improving the frailty evaluation tools and applications for bladder cancer patients research provides reference.
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Bladder cancer is the most common malignancy of the urinary system. Compound Kushen Injection (CKI) is a Chinese medicinal preparation that has been widely used in the treatment of various types of cancers in the past two decades. However, the pharmacological effect of CKI on bladder cancer is not still completely understood. In the current study, network pharmacology combined with bioinformatics was used to elucidate the therapeutic mechanism and potential targets of CKI in bladder cancer. The mechanism by which CKI was effective against bladder cancer was further verified in vitro using human bladder cancer cell line T24. Network pharmacology analysis identified 35 active compounds and 268 target genes of CKI. Bioinformatics data indicated 5500 differentially expressed genes associated with bladder cancer. Common genes of CKI and bladder cancer suggested that CKI exerted anti-bladder cancer effects by regulating genes such as MMP-9, JUN, EGFR, and ERK1. Functional enrichment analysis indicated that CKI exerted therapeutic effects on bladder cancer by regulating certain biological processes, including cell proliferation, cell migration, and cell apoptosis. In addition, Kyoto Encyclopedia of Genes and Genomes enrichment analysis implicated pathways related to cancer, bladder cancer, and the PI3K-Akt signaling pathway. Consistently, cell experiments indicated that CKI inhibited the proliferation and migration of T24 cells, and induced their apoptosis. Moreover, RT-qPCR and Western blot results demonstrated that CKI was likely to treat bladder cancer by down-regulating the gene and protein expression of MMP-9, JUN, EGFR, and ERK1. CKI inhibited the proliferation and migration, and induced the apoptosis of T24 bladder cancer cells through multiple biological pathways and targets. CKI also exhibited significant effects on the regulation of key genes and proteins associated with bladder cancer. Overall, our findings provide solid evidence and deepen current understanding of the therapeutic effects of CKI for bladder cancer, and further support its clinical use.
Subject(s)
Computational Biology , Drugs, Chinese Herbal , Humans , Network Pharmacology , Phosphatidylinositol 3-Kinases , Urinary Bladder Neoplasms/geneticsABSTRACT
OBJECTIVES@#Bladder cancer is one of the most common urothelial tumors with high incidence and mortality rates. Although it has been reported that microRNA (miR)-133b can regulate tumorigenesis of bladder cancer, the mechanism remains unclear. Sex-determining region Y-box transcription factor 4 (SOX4) exhibits an important role in tumorigenesis, but it is unclear whether SOX4 and miR-133b are associated with regulation of pathogenesis of bladder cancer. This study aims to determine the expressions of SOX4 and miR-133b in bladder cancer tissues and cells, investigate their effects on the proliferation, colony formation, and invasion of bladder cancer cells, and to explore the association between miR-133b and SOX4 in regulating biological featurss of bladder cancer cells.@*METHODS@#The bladder cancer and adjacent tissue samples of 10 patients who underwent surgical resection in the Second Xiangya Hospital of Central South Universty from Januray to June 2015 were obtained. The levels of miR-133b were tested by real-time PCR, and the protein levels of SOX4 were evaluated using Western blotting in bladder cancer tissues, matched adjacent tissues, and cell lines. The correlation between miR-133b expression and SOX4 expression in bladder cancer tissues was analyzed. Using the online database TargetScan, the relationship between SOX4 and miR-133b was predicted. MiR-133b mimics, miR-133b inhibitor, and short hairpin RNA (shRNA)-SOX4 were transfected into T24 cells by Lipofectamine 2000. The relationship between miR-133b and SOX4 was also verified by a dual-luciferase reporter assay. The proliferation of T24 cells cultured for 0, 12, 48, 72, and 96 h was evaluated by cell counting kit-8 (CCK-8) assay. The colony formation capacity of bladder cancer cells was tested after 14-day culture, and cell invasion capacity was evaluated with Transwell invasion assay.@*RESULTS@#Bladder cancer tissue and bladder cancer cells had low level of miR-133b but high level of SOX4, compared with matched adjacent tissues and normal bladder epithelial cells. A negative correlation between miR-133b mRNA and SOX4 protein levels in bladder cancer tissues was also found (r=-0.84). The results of online database TargetScan showed that miR-133b targets at SOX4, and overexpression of miR-133b significantly attenuated the expression of SOX4 in T24 cells. Both overexpression of miR-133b and knockdown of SOX4 significantly inhibited the proliferation, colony formation, and invasion capacity of bladder cancer cells in vitro. SOX4 down-regulation restored the effects of miR-133b inhibitor on the proliferation, colony formation, and invasion capacity of T24 cells.@*CONCLUSIONS@#The up-regulation of SOX4 contributes to the progression of bladder cancer, and miR-133b can regulate the proliferation, colony formation, and invasion of bladder cancer cells via inhibiting SOX4.
Subject(s)
Carcinogenesis/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Epithelial Cells/metabolism , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs/genetics , SOXC Transcription Factors/genetics , Urinary Bladder , Urinary Bladder Neoplasms/geneticsABSTRACT
OBJECTIVE@#To explore the molecular mechanism by which microRNA let-7g-3p regulates biological behaviors of bladder cancer cells.@*METHODS@#The expression levels of let-7g-3p in bladder cancer and adjacent tissues, normal bladder epithelial cells (HUC cells) and bladder cancer cells (T24, 5637 and EJ cells) were detected using qRT- PCR. T24 cells were transfected with let-7g-3p mimic or inhibitor, and the changes in cell proliferation, migration, invasion, and apoptosis were examined. Transcriptome sequencing was carried out in cells overexpressing let-7g-3p, and the results of bioinformatics analysis, double luciferase reporter gene assay, qRT-PCR and Western blotting confirmed that HMGB2 gene was the target gene of let-7g-3p. The expression of HMGB2 was examined in HUC, T24, 5637 and EJ cells, and in cells with HMGB2 knockdown, the effect of let-7g-3p knockdown on the biological behaviors were observed.@*RESULTS@#qRT-qPCR confirmed that let-7g-3p expression was significantly lower in bladder cancer tissues and cells (P < 0.01). Overexpression of let-7g-3p inhibited cell proliferation, migration and invasion, and promoted cell apoptosis, while let-7g-3p knock-down produced the opposite effects. Bioinformatics and transcriptome sequencing results showed that HMGB2 was the key molecule that mediate the effect of let-7g-3p on bladder cancer cells. Luciferase reporter gene assay, qRT-PCR and Western blotting all confirmed that HMGB2 was negatively regulated by let-7g-3p (P < 0.01). Knocking down HMGB2 could partially reverse the effect of let-7g-3p knockdown on the biological behaviors of the bladder cancer cells.@*CONCLUSION@#The microRNA let-7g-3p can inhibit the biological behavior of bladder cancer cells by negatively regulating HMGB2 gene.
Subject(s)
Apoptosis , Cell Line, Tumor , Cell Movement/physiology , Cell Proliferation , Epithelial Cells/metabolism , Gene Expression Regulation, Neoplastic , HMGB2 Protein/metabolism , Humans , MicroRNAs/metabolism , Urinary Bladder , Urinary Bladder Neoplasms/geneticsABSTRACT
OBJECTIVE@#To determine the optimal cystoscopic frequency for intermediate-risk non-muscle invasive bladder cancer.@*METHODS@#Patients with intermediate-risk non-muscle invasive bladder cancer, who underwent transurethral resection of bladder tumor in Peking University People's Hospital from January 2001 to October 2019, were retrospectively analyzed. Their clinical, pathological and follow-up data were collected. In postoperative 2-year period, the patients were underwent cystoscopy every 3 to 6 months. Depending on recurrence and progression of the patients, we hypothesized three strategies of surveillance intensity in the first 2 years after surgery: model 1: 3-month intervals, model 2: 6-month intervals, and model 3: 12-month intervals. The differences in the numbers and time of delayed detection of recurrence and progression were compared among the three models.@*RESULTS@#A total of 185 patients were enrolled, including 144 males (77.8%) and 41 females (22.2%). The median age was 68 (59-76) years. There were 118 cases (63.8%) with single tumor and 67 cases (36.2%) with multiple tumor. Of the patients 179 (96.8%) had stage Ta and 6 (3.2%) had stage T1. There were 108 cases (58.4%) with high-grade disease and 77 cases (41.6%) with low-grade disease. During the follow-up period of the first 2 years, 52 patients (28.1%) had recurrence, 133 cases (71.9%) had no recurrence, 11 cases (5.9%) had progression and 174 cases (94.1%) had no progression. Compared with model 1, 29 (55.8%) delayed detection of recurrence in model 2 vs. 41 (78.8%) delayed detection of recurrence in model 3, and the difference was statistically significant (P=0.012). The median delayed time of detecting recurrence was 1.00 months in model 1, 1.99 months in model 2 and 4.19 months in model 3, respectively. There were statistically significant differences between mode 1 and model 3 (P=0.001), and between model 2 and model 3 (P=0.013). Compared with model 1, 5 (45.4%) delayed detection of progression in model 2 vs. 8 (72.7%) delayed detection of progression in model 3, and the difference was not statistically significant. The median delayed time of detecting progression was 1.00 month in model 1, 2.00 months in model 2 and 3.00 months in model 3, respectively. There was no statistically significant difference among them.@*CONCLUSION@#Although providing slightly slower detection of tumor recurrence and progression, compared with 3-month intervals of cystoscopy, 6-month intervals do not result in serious adverse outcomes and reduce cost and pain of the patients, which is feasible in intermediate-risk non-muscle invasive bladder cancer.
Subject(s)
Aged , Cystoscopy , Disease Progression , Female , Humans , Male , Neoplasm Recurrence, Local/diagnosis , Retrospective Studies , Urinary Bladder Neoplasms/surgeryABSTRACT
The aim of this study was to investigate the incidence of erectile dysfunction (ED) in nonmuscle-invasive bladder cancer (NMIBC) patients before and after transurethral resection (TUR) in China. Clinical data from 165 male patients with NMIBC who received adjuvant intravesical chemotherapy after TUR in Neijiang First People's Hospital (Neijiang, China) between January 2010 and June 2019 were retrospectively reviewed. The sexual function of these patients was evaluated before and 1.5 years after initial TUR by the International Index of Erectile Function-5 (IIEF-5). An age-specific subanalysis was performed among the patients: <45 years old (Group 1, n = 19) and ≥45 years old (Group 2, n = 146). Before and 1.5 years after TUR, the incidence rates of ED in Group 1 were 15.8% and 52.6%, and those in Group 2 were 54.1% and 61.0%, respectively. The difference between groups was statistically significant at the preoperative stage (15.8% vs 54.1%, P = 0.002) but not at the postoperative stage (52.6% vs 61.0%, P = 0.562). Compared with the preoperative stage, the incidence of ED at the postoperative stage was increased significantly in Group 1 (15.8% vs 52.6%, P = 0.017) but not in Group 2 (54.1% vs 61.0%, P = 0.345). In conclusion, the incidence of ED increased in male NMIBC patients under the age of 45 years after TUR in China. These patients should be offered professional counseling during the follow-up period.
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Administration, Intravesical , Erectile Dysfunction , Humans , Male , Middle Aged , Neoplasm Invasiveness , Retrospective Studies , Urinary Bladder NeoplasmsABSTRACT
ObjectiveTo predict the potential targets and possible related signaling pathways of Salviae Miltiorrhizae Radix et Rhizoma against bladder cancer （BC） based on network pharmacology and verify the potential molecular mechanism through in vitro cell experiment. MethodActive components of Salviae Miltiorrhizae Radix et Rhizoma were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and BC-related targets were searched from GeneCards and Online Mendelian Inheritance in Man （OMIM）. Via Venny2.1， the potential targets of Salviae Miltiorrhizae Radix et Rhizoma against BC were screened out and the Venn diagram was plotted. Protein-protein interaction （PPI） network was constructed by STRING， followed by Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Gnomes （KEGG） pathway enrichment with DAVID. Cell Counting Kit-8 （CCK-8） assay was employed to detect the inhibitory effect of tanshinone ⅡA （Tan ⅡA）， cryptotanshinone （CPT）， and luteolin （LUT） at different concentration （0， 1， 2， 4， 8， 16， 32 μmol·L-1） on the proliferation of BC T24 and 5637 cells， propidium iodide （PI） staining to analyze the apoptosis of 5637 cells induced by Tan ⅡA， CPT， and LUT （0， 4， 8 μmol·L-1）， and Western blotting to detect the regulatory effect of Tan ⅡA （0， 4， 8， 16 μmol·L-1） on the expression of key target proteins. ResultA total of 65 active components and 39 anti-BC targets of Salviae Miltiorrhizae Radix et Rhizoma were screened out. The anti-BC targets were mainly involved in the KEGG pathways of neuron-ligand-receptor interaction， phosphatidylinositol 3-kinases （PI3K）/protein kinase B （Akt） signaling pathway， epidermal growth factor receptor （EGFR） tyrosine kinase inhibitor resistance， and hypoxia inducible factor （HIF）-1 signaling pathway. As for the CCK-8 assay， compared with the blank group， Tan ⅡA， CPT， and LUT significantly inhibited the proliferation of T24 and 5637 cells， particularly the 5637 cells. The half maximal inhibitory concentration （IC50） of Tan ⅡA on 5637 cells was significantly lower than that of CPT and LUT. Moreover， compared with the blank group， Tan ⅡA， CPT， and LUT all induced the apoptosis of 5637 cells， and the effect followed the order of Tan ⅡA>CPT>LUT （P<0.05）. Western blot showed that Tan ⅡA significantly reduced the expression of EGFR， p-PI3K， and p-Akt in 5637 cells in a concentration-dependent manner compared with the blank group （P<0.05）. ConclusionSalviae Miltiorrhizae Radix et Rhizoma exerts therapeutic effect on BC through multiple components， multiple targets， and multiple pathways. The mechanism is the likelihood that it down-regulates the expression of EGFR， p-PI3K， and p-Akt proteins， thus further inhibits cell proliferation， and induces apoptosis.
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ObjectiveTo investigate the role of protein kinase B （Akt） overexpression in the inhibition of human bladder cancer 5637 cell proliferation by erianin and related mechanisms. MethodThe 5637 cells stably over-expressing Akt were induced using the lentivirus vector. The 5637 cells infected with the empty vector were classified into blank group. Then the Akt group， empty vector combined with erianin （62.5 μg·L-1） group， and Akt combined with erianin （62.5 μg·L-1） group were set up. The cell viability was detected by cell counting kit-8 （CCK-8） assay， and the clone formation of 5637 cells in each group was determined in the clone formation experiment. The cell cycle distribution was detected by flow cytometry. Western blot was used to assay the protein expression levels of phosphorylated （p）-Akt， Akt， p21. The glycolysis of 5637 cells was determined in glucose uptake and lactate secretion assays. ResultCompared with the blank group， erianin inhibited the proliferation of bladder cancer 5637 cells （P<0.05）. Overexpression of Akt partially reversed the inhibitory effect of erianin on the proliferation of bladder cancer 5637 cells （P<0.05）. Clone formation assay showed that erianin inhibited the clone formation of bladder cancer 5637 cells （P<0.05）， which was partially reversed by the overexpressed Akt （P<0.05）. As revealed by comparison with the blank group， erianin arrested the bladder cancer 5637 cells in G1 phase （P<0.05）， which was also reversed by the overexpressed Akt （P<0.05）. Western bolt showed that erianin promoted the expression of p21 but suppressed the expression of p-Akt and Akt （P<0.05）. By contrast， the overexpression of Akt down-regulated the elevated p21 protein expression induced by erianin （P<0.05）. Compared with the blank group， erianin inhibited the glucose uptake and lactate secretion of bladder cancer 5637 cells （P<0.05）. Overexpression of Akt weakened the inhibitory effect of erianin against the glycolysis of 5637 cells （P<0.05）. ConclusionErianin is able to inhibit the proliferation of bladder cancer 5637 cells， promote the expression of p21， and inhibit the expression of p-Akt. Overexpressed Akt reduces the inhibitory effect of erianin on the proliferation of bladder cancer 5637 cells， suggesting that Akt plays an important role in the inhibition of 5637 cell proliferation by erianin， which has provided a new target for the application of erianin in the treatment of bladder cancer.
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Bladder cancer is the most prevalent malignant tumor in the urinary tract in China. Western medical treatments， including long-term regular endoscopy， intravesical chemotherapy， immunotherapy， and radical cystectomy， are effective， whereas the high recurrence rate still plagues both doctors and patients. Among the classical signaling pathways involved in the formation and progression of bladder cancer， the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway is a key one. Modern pharmacological studies have demonstrated that Chinese herbal medicines and their monomer components can alleviate the discomfort， prolong the survival， and improve the quality of life of the patients undergoing tumor treatment. The relevant literature in the past decade has revealed that flavonoids， terpenoids， polysaccharides， gambogic acids， bibenzyls， and alkaloids from Chinese herbal medicines regulate the PI3K/Akt signaling pathway to play a role in the proliferation， apoptosis， invasion， migration， drug resistance， and autophagy of bladder cancer cells， thereby exerting the activity against bladder cancer. Although some targets and the potential mechanisms of the monomer components in the treatment of bladder cancer have been clarified， the research on the monomer components is limited to in vitro cellular experiments and animal experiments. Researchers face the great challenge in the application of the monomer components from Chinese herbal medicines into clinical practice. We summarized the recent studies about the regulatory effects of monomer components from Chinese herbal medicines on the PI3K/Akt signaling pathway in bladder cancer， aiming to give insights into the research on the drug therapy of bladder cancer and the underlying mechanism.
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Bladder cancer is the most prevalent malignant tumor in the urinary tract in China. Western medical treatments， including long-term regular endoscopy， intravesical chemotherapy， immunotherapy， and radical cystectomy， are effective， whereas the high recurrence rate still plagues both doctors and patients. Among the classical signaling pathways involved in the formation and progression of bladder cancer， the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway is a key one. Modern pharmacological studies have demonstrated that Chinese herbal medicines and their monomer components can alleviate the discomfort， prolong the survival， and improve the quality of life of the patients undergoing tumor treatment. The relevant literature in the past decade has revealed that flavonoids， terpenoids， polysaccharides， gambogic acids， bibenzyls， and alkaloids from Chinese herbal medicines regulate the PI3K/Akt signaling pathway to play a role in the proliferation， apoptosis， invasion， migration， drug resistance， and autophagy of bladder cancer cells， thereby exerting the activity against bladder cancer. Although some targets and the potential mechanisms of the monomer components in the treatment of bladder cancer have been clarified， the research on the monomer components is limited to in vitro cellular experiments and animal experiments. Researchers face the great challenge in the application of the monomer components from Chinese herbal medicines into clinical practice. We summarized the recent studies about the regulatory effects of monomer components from Chinese herbal medicines on the PI3K/Akt signaling pathway in bladder cancer， aiming to give insights into the research on the drug therapy of bladder cancer and the underlying mechanism.
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ObjectiveTo investigate the perioperative safety and complications of radical cystectomy （RC）. MethodsThe clinicopathological indexes， postoperative complications and prognosis of patients who underwent RC at Sun Yat-sen University Cancer Centre from January 2001 to August 2020 were retrospectively collected and analyzed. Among them， patients from 2011 to 2020 were further analyzed and compared according to the open surgery group （ORC）， laparoscopic group （LRC） and robot-assisted laparoscopic group （RARC）. Independent sample t test， Chi-square test， K-M survival curve and other statistical methods were used to describe the complications and prognosis of patients， and Logistic regression was used to analyze the influencing factors of complications of RC. ResultsAmong the 1041 patients who underwent RC surgery from 2001 to 2020， the median age was 63 （55-69） years. In terms of the gender ratio， men were the majority at 86 percent. Compared with that of the first 10 years， the complication rate of the second 10 years decreased significantly （37.4% vs. 26.7%）. Complications of 667 patients who underwent RC surgery were analyzed from 2010 to 2020， with a median follow-up of 34 months. A total of 415 patients were enrolled in the ORC group， 161 in the LRC group， and 91 in the RARC group. Ileal conduit （659 cases， 63.3%） accounted for the highest proportion of all urinary diversion methods， while orthotopic neobladder accounted for the second （343 cases， 32.9%）. The incidence of all grade complications was 30.5%， and the most common complication was urinary complications. The incidence of total complications and grade ≥3 complications in the ORC group was higher than that in the LRC and RARC groups （Total complications： ORC， 30.8%； LRC，21.1%， RARC，24.2%； P=0.047； Grade ≥3 complications： ORC， 14.7%； LRC，9.3%； RARC，6.6%； P=0.043）. ConclusionsWith the improvement of surgical techniques and experience， the incidence of recent postoperative complications after radical resection of bladder cancer in our center has decreased. Compared with open surgery， minimally invasive surgery has some advantages in reducing the complication rate.
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Abstract Objective: Long Non-Coding RNAs (LncRNAs) act as an indispensable role in cancer development. The study aimed to investigate the role and mechanism of lncRNA Small Nucleolar RNA Host Gene 1 (SNHG1) in Bladder Cancer (BC) progression. Method: The expression, prognostic value, diagnostic value, and correlation of SNHG1, Enhancer of Zeste 2 polycomb repressive complex 2 subunit (EZH2), and Kruppel Like Factor 2 (KLF2) were analyzed through bioinformatics analysis. The expression was also validated in BC tissues and cell lines. Besides, their regulation and binding were tested via qPCR, Western blot, Dual-Luciferase Reporter Assay (DLRA), Argonaute RISC catalytic component 2-RNA Immunoprecipitation (AGO2-RIP), and Chromatin Immunoprecipitation (ChIP). A xenograft model in nude mice was also established. Results: SNHG1 was significantly overexpressed in BC tissues and cells. Importantly, SNHG1 was associated with poor survival, and ROC curves revealed high diagnostic values. Moreover, by CCK8, wound healing, transwell, and Western blot analysis, SNHG1 knockdown significantly inhibited the proliferation, migration, invasion, and epithelial-mesenchymal transition of BC cells. Additionally, in vivo experiments showed that silencing SNHG1 hindered tumorigenesis and tumor growth. Regarding mechanism, the results of AGO2-RIP, ChIP or DLRA showed that SNHG1 played different roles at diverse subcellular sites. In the cytoplasm, SNHG1 acted as a competing endogenous RNA for miR-137-3p to promote EZH2 expression. In the nucleus, SNHG1 could interact with EZH2 to inhibit KLF2 transcription. Conclusion: Our study elucidated that SNHG1 formed a regulatory network and played an oncogenic role in BC, which provided a novel therapeutic target for BC treatment.
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RESUMEN Introducción: el cáncer de la vejiga es la segunda neoplasia urológica. En Cuba constituye la séptima causa de cáncer en el sexo masculino y entre las primeras quince, cuando se combinan ambos sexos. Objetivo: evaluar el comportamiento del cáncer de vejiga en pacientes del Hospital Universitario Comandante "Faustino Pérez Hernández". Materiales y Métodos: se realizó un estudio observacional, descriptivo y transversal en el período comprendido desde diciembre de 2014 hasta enero de 2020. Los pacientes se dividieron en tres grupos tratados con cirugía de mínimo acceso, cirugía abierta y no operados, se describieron los grupos histológicos y estadiaje tumoral y se les aplicó tratamiento según protocolo del servicio, sus complicaciones y la presencia de recidivas tumorales también fueron descritas. En el universo se incluyeron en el estudio 222 pacientes diagnosticados de cáncer de vejiga. Resultados: se comprobó que el mayor número de pacientes diagnosticados con cáncer de vejiga son del sexo masculino, el tipo histológico es el carcinoma de células uroteliales de bajo grado y el estadio T1. Las recidivas se presentaron antes de los 5 años en el 10,8% de los casos. 196 pacientes presentaron complicaciones. Conclusiones: el cáncer de vejiga es más frecuente en las edades comprendidas entre 60 a 69 años, las recidivas aparecieron mayormente entre 1 y 3 años. Se presentó complicaciones en 196 pacientes, siendo la cirugía la modalidad terapéutica que mayor por ciento tuvo con un 32.22% y las infecciones son las complicaciones más frecuentes (AU).
SUMMARY Introduction: Cancer of the bladder (CV) is the second urological neoplasm. In Cuba it constitutes the seventh cause of cancer in males and among the first fifteen, when both sexes are combined. Objective: To evaluate the behavior of bladder cancer (CV) in patients of the Faustino Pérez Hernández Hospital. Materials and methods: An observational, descriptive and cross-sectional study was carried out in the period from December 2014 to January 2020. The patients were divided into 3 groups treated with Minimum Access Surgery (CMA), Open Surgery (CA) and No Operated (NO), the histological groups and tumor staging were described and treatment was applied according to the service protocol, their complications and the presence of tumor recurrences were also described.Universe: 222 patients diagnosed with bladder cancer were included in the study. Results: It was found that the greatest number of patients diagnosed with CV are male, the histological type is low-grade urothelial cell carcinoma and stage T1. Recurrences occurred before 5 years in 10.8% of cases. 196 patients presented complications. Conclusions: The CV is more frequent in the ages between 60 to 69 years, the recurrences appeared mainly between 1 and three years. Complications occurred in 196 patients, with Surgery being the therapeutic modality with the highest percentage with 32.22% and infections being the most frequent complications (AU).
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Humans , Urinary Bladder Neoplasms/epidemiology , Carcinoma/epidemiology , Infections/etiology , Urinary Bladder Neoplasms/surgery , Urinary Bladder Neoplasms/complications , Urinary Bladder Neoplasms/diagnosis , Carcinoma/surgery , Carcinoma/complications , Carcinoma/diagnosis , Epidemiology, Descriptive , Cross-Sectional Studies , Observational StudyABSTRACT
Platycodin D (PD) is a major constituent of Platycodon grandiflorum and has multiple functions in disease control. This study focused on the function of PD in bladder cancer cell behaviors and the molecules involved. First, we administered PD to the bladder cancer cell lines T24 and 5637 and the human uroepithelial cell line SV-HUC-1. Cell viability and growth were evaluated using MTT, EdU, and colony formation assays, and cell apoptosis was determined using Hoechst 33342 staining and flow cytometry. The microRNAs (miRNAs) showing differential expression in cells before and after PD treatment were screened. Moreover, we altered the expression of miR-129-5p and PABPC1 to identify their functions in bladder cancer progression. We found that PD specifically inhibited the proliferation and promoted the apoptosis of bladder cancer cells; miR-129-5p was found to be partially responsible for the cancer-inhibiting properties of PD. PABPC1, a direct target of miR-129-5p, was abundantly expressed in T24 and 5637 cell lines and promoted cell proliferation and suppressed cell apoptosis. In addition, PABPC1 promoted the phosphorylation of PI3K and AKT in bladder cancer cells. Altogether, PD had a concentration-dependent suppressive effect on bladder cancer cell growth and was involved in the upregulation of miR-129-5p and the subsequent inhibition of PABPC1 and inactivation of PI3K/AKT signaling.