Creation of bladder assembloids mimicking tissue regeneration and cancer.

Current organoid models are limited by their inability to mimic mature organ architecture and associated tissue microenvironments1,2. Here we create multilayer bladder 'assembloids' by reconstituting tissue stem cells with stromal components to represent an organized architecture with an epithelium surrounding stroma and an outer muscle layer. These assembloids exhibit characteristics of mature adult bladders in cell composition and gene expression at the single-cell transcriptome level, and recapitulate in vivo tissue dynamics of regenerative responses to injury. We also develop malignant counterpart tumour assembloids to recapitulate the in vivo pathophysiological features of urothelial carcinoma. Using the genetically manipulated tumour-assembloid platform, we identify tumoural FOXA1, induced by stromal bone morphogenetic protein (BMP), as a master pioneer factor that drives enhancer reprogramming for the determination of tumour phenotype, suggesting the importance of the FOXA1-BMP-hedgehog signalling feedback axis between tumour and stroma in the control of tumour plasticity.

Loss of UTX/KDM6A and the activation of FGFR3 converge to regulate differentiation gene-expression programs in bladder cancer.

Bladder cancer prognosis is closely linked to the underlying differentiation state of the tumor, ranging from the less aggressive and most-differentiated luminal tumors to the more aggressive and least-differentiated basal tumors. Sequencing of bladder cancer has revealed that loss-of-function mutations in chromatin regulators and mutations that activate receptor tyrosine kinase (RTK) signaling frequently occur in bladder cancer. However, little is known as to whether and how these two types of mutations functionally interact or cooperate to regulate tumor growth and differentiation state. Here, we focus on loss of the histone demethylase UTX (also known as KDM6A) and activation of the RTK FGFR3, two events that commonly cooccur in muscle invasive bladder tumors. We show that UTX loss and FGFR3 activation cooperate to disrupt the balance of luminal and basal gene expression in bladder cells. UTX localized to enhancers surrounding many genes that are important for luminal cell fate, and supported the transcription of these genes in a catalytic-independent manner. In contrast to UTX, FGFR3 activation was associated with lower expression of luminal genes in tumors and FGFR inhibition increased transcription of these same genes in cell culture models. This suggests an antagonistic relationship between UTX and FGFR3. In support of this model, UTX loss-of-function potentiated FGFR3-dependent transcriptional effects and the presence of UTX blocked an FGFR3-mediated increase in the colony formation of bladder cells. Taken together, our study reveals how mutations in UTX and FGFR3 converge to disrupt bladder differentiation programs that could serve as a therapeutic target.

Prunetin inhibits nitric oxide activity and induces apoptosis in urinary bladder cancer cells via CASP3 and TNF-α genes.

BACKGROUND: Urinary bladder cancer (UBC) is considered one of the most prevalent malignant tumors worldwide. Complementary and integrative approaches for the treatment of bladder cancer, such as the intake of isoflavonoid phytoestrogens, are of increasing interest due to the risk of mortality and long-term morbidity associated with surgical procedures. The biological effects of prunetin, one of the less-studied phytoestrogens, have not yet been examined in this respect. Therefore, this study aimed to explore the efficacy of prunetin on UBC cells (RT-4). METHODS AND RESULTS: The cytotoxicity and nitric oxide synthase activities of prunetin were determined in cell cultures. The expression of apoptosis-related genes was determined with RT-PCR. Cell cycle assays were performed using a flow cytometer and cellular apoptotic rate was measured. The results suggested that prunetin has cytotoxic effects at 21.11 µg/mL on RT-4 cells. Flow cytometry analysis showed that prunetin induced apoptosis and arrested th cell cycle in the G0/G1 phase. Prunetin exposure was associated with increases in CASP3 and TNF-α gene expression in RT-4 cells at doses of 21.11 and 42.22 µg/mL, respectively. Strong nitric oxide inhibition was observed at IC50 of 5.18 µg/mL under macrophage mediated inflammatory circumstances. CONCLUSIONS: Prunetin possesses anti-cancer properties and may be a candidate compound for the prevention of UBC. This is the first study that evaluated prunetin for its in vitro antitumor activities, clarified its possible apoptotic molecular mechanism and provided novel insights into its anti-inflammatory nature and effects on the expression of related key genes.

Comprehensive Gene Expression Analyses of Immunohistochemically Defined Subgroups of Muscle-Invasive Urinary Bladder Urothelial Carcinoma.

A number of urinary bladder urothelial carcinoma (UB UC) mRNA-based classification systems have been reported. It also has been observed that treatment response and prognosis are different for each molecular subtype. In this study, cytokeratin (CK)5/6 and CK20 immunohistochemistry (IHC) were performed, and IHC-based subgroup classification was applied. UB UC was classified into CK5/6 single-positive (SP), CK20 SP, double-positive (DP) and double-negative (DN) subgroups, and transcriptional analysis was performed. The results of gene ontology (GO) terms and functional analysis using differentially expressed genes indicate that, CK5/6 SP and DP subgroups were enriched in cell migration, immune activation, interleukin 6-Janus kinase-signal transducer and activator of transcription 3 (IL6-JAK-STAT3) signaling pathway and tumor necrosis factor-α signaling via the nuclear factor-κB (NF-κB) signaling pathway signature gene. In addition, compared with the other subgroups, the DN subgroup showed inhibited cell movement, cell migration, and cell activation. Furthermore, in survival analysis, the CK5/6 SP subgroup was significantly associated with poor progression-free survival (p = 0.008). The results of our study indicate that the CK5/6 positive subgroup exhibited high gene expression signature related to aggressive behavior and exhibited worse clinical outcome.

Vitamin A and Retinoids in Bladder Cancer Chemoprevention and Treatment: A Narrative Review of Current Evidence, Challenges and Future Prospects.

Bladder cancer (BC) is the tenth most common cancer worldwide with a high recurrence rate, morbidity and mortality. Therefore, chemoprevention and improved treatment of BC are of paramount importance. Epidemiological studies suggest that adequate vitamin A intake may be associated with reduced BC risk. In addition, retinoids, natural and synthetic derivatives of vitamin A, are intensively studied in cancer research due to their antioxidant properties and their ability to regulate cell growth, differentiation, and apoptosis. Findings from in vivo and in vitro models of BC show great potential for the use of retinoids in the chemoprevention and treatment of BC. However, translation to the clinical practice is limited. In this narrative review we discuss: (i) vitamin A and retinoid metabolism and retinoic acid signalling, (ii) the pathobiology of BC and the need for chemoprevention, (iii) the epidemiological evidence for the role of dietary vitamin A in BC, (iv) mechanistic insights obtained from in vivo and in vitro models, (v) clinical trials of retinoids and the limitations of retinoid use, (vi) novel systems of retinoid delivery, and (vii) components of retinoid signalling pathways as potential novel therapeutic targets.

The natural history of untreated muscle-invasive bladder cancer.

OBJECTIVE: To describe the natural history of untreated muscle-invasive bladder cancer (MIBC) and compare the oncological outcomes of treated and untreated patients. PATIENTS AND METHODS: We utilised a database encompassing all patients with newly diagnosed bladder cancer in Stockholm, Sweden between 1995 and 1996. The median follow-up for survivors was 14.4 years. Overall, 538 patients were diagnosed with bladder cancer of whom 126 had clinically localised MIBC. Patients were divided into two groups: those who received radical cystectomy or radiation therapy, and those who did not receive any form of treatment. Multivariable Cox or competing-risks regressions were adopted to predict metastasis, overall survival (OS), and cancer-specific mortality (CSM), when appropriate. Analyses were adjusted for age at diagnosis, sex, tumour stage, clinical N stage, and treatment. RESULTS: In all, 64 (51%) patients did not receive any definitive local treatment. In the untreated group, the median (interquartile range) age at diagnosis was 79 (63-83) vs 69 (63-74) years in the treated group (P < 0.001). Overall, 109 patients died during follow-up. At 6 months after diagnosis, 38% of the untreated patients had developed metastatic disease and 41% had CSM. The 5-year OS rate for untreated and treated patients was 5% (95% confidence interval [CI] 1, 12%) vs 48% (95% CI 36, 60%), respectively. Patients not receiving any treatment had a 5-year cumulative incidence of CSM of 86% (95% CI 75, 94%) vs 48% (95% CI 36, 60%) for treated patients. Untreated patients had a higher risk of progression to metastatic disease (hazard ratio [HR] 2.40, 95% CI 1.28, 4.51; P = 0.006), death from any cause (HR 2.63, 95% CI 1.65, 4.19; P < 0.001) and CSM (subdistribution HR 2.02, 95% CI 1.24, 3.30; P = 0.004). CONCLUSIONS: Untreated patients with MIBC are at very high risk of near-term CSM. These findings may help balance the risks vs benefits of integrating curative intent therapy particularly in older patients with MIBC.

Experimental study of the difference in deformation between normal and pathological, renal and bladder, cells induced by acoustic radiation force.

Previous studies have shown that alterations in the mechanical properties of cells may be associated with the onset and progression of some forms of pathology. In this paper, an experimental study of two types of cells, renal (cancer) and bladder (cancer) cells, is described which used acoustic radiation force (ARF) generated by a high-frequency ultrasound focusing transducer and performed on the operating platform of an inverted light microscope. Comparing images of cancer cells with those of normal cells of the same kind, we find that the cancer cells are more prone to deform than normal cells of the same kind under the same ARF. In addition, cancer cells with higher malignancy are more deformable than those with lower malignancy. This means that the deformability of cells may be used to distinguish diseased cells from normal ones, and more aggressive cells from less aggressive ones, which may provide a more rapid and accurate method for clinical diagnosis of urological disease in the future.

Variables associated with survival in patients with invasive bladder cancer with and without surgery.

We recorded the survival of 141 patients assessed for radical cystectomy, which included cardiopulmonary exercise testing. The median Kaplan-Meier survival estimates were: 1540 days for the whole cohort; 2200 days after cystectomy scheduled (n = 108); and 843 days without surgery. The mortality hazard remained double that expected for a matched general population, but survival was better in patients scheduled for surgery than those who were not: the mortality hazard ratio (95%CI) after cystectomy was 0.43 (0.26-0.73) the mortality hazard without surgery, p = 0.001. The mortality hazard ratios for the three-variable Bayesian Model Averaging survival model for all 141 patients were: referral for surgery (0.5); haemoglobin concentration (0.98); and efficiency of carbon dioxide output (1.05). Efficiency of carbon dioxide output was the single variable in the postoperative model (n = 108), mortality hazard 1.08 (per unit increase). The ratio of observed to expected peak oxygen consumption associated best with mortality in 33 patients not referred for surgery, hazard ratio 0.001. Our results can inform consultations with patients with invasive bladder cancer and suggest that interventions to increase fitness and haemoglobin may improve survival in patients who do and who do not undergo radical cystectomy.

Self-perceived burden and its associations with health-related quality of life among urologic cancer patients.

OBJECTIVE: This study examined the prevalence of self-perceived burden (SPB) and its association with health-related quality of life (HRQoL) among urologic cancer patients. METHODS: This was a prospective, cross-sectional study. A total of 429 respondents diagnosed with urologic cancers (prostate, bladder and renal cancer) from Sarawak General Hospital and Subang Jaya Medical Centre in Malaysia were interviewed by using a structured questionnaire. SPB and HRQoL were measured by the Self-perceived Burden Scale and the Functional Assessment of Cancer Therapy-General 7 Item Scale respectively. RESULTS AND CONCLUSION: Self-perceived burden was experienced by 73.2% of the respondents. Respondents who had a lower education level, a monthly household income

SARS-CoV-2 Infection and High-Risk Non-Muscle-Invasive Bladder Cancer: Are There Any Common Features?

BACKGROUND: The new severe acute respiratory syndrome virus (SARS-CoV-2) outbreak is a huge health, social and economic issue and has been declared a pandemic by the World Health Organization. Bladder cancer, on the contrary, is a well-known disease burdened by a high rate of affected patients and risk of recurrence, progression and death. SUMMARY: The coronavirus disease (COVID-19 or 2019-nCoV) often involves mild clinical symptoms but in some cases, it can lead to pneumonia with acute respiratory distress syndrome and multiorgan dysfunction. Factors associated with developing a more severe disease are increased age, obesity, smoking and chronic underlying comorbidities (including diabetes mellitus). High-risk non-muscle-invasive bladder cancer (NMIBC) progression and worse prognosis are also characterized by a higher incidence in patients with risk factors similar to COVID-19. Immune system response and inflammation have been found as a common hallmark of both diseases. Most severe cases of COVID-19 and high-risk NMIBC patients at higher recurrence and progression risk are characterized by innate and adaptive immune activation followed by inflammation and cytokine/chemokine storm (interleukin [IL]-2, IL-6, IL-8). Alterations in neutrophils, lymphocytes and platelets accompany the systemic inflammatory response to cancer and infections. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for example have been recognized as factors related to poor prognosis for many solid tumors, including bladder cancer, and their role has been found important even for the prognosis of SARS-CoV-2 infection. Key Messages: All these mechanisms should be further analyzed in order to find new therapeutic agents and new strategies to block infection and cancer progression. Further than commonly used therapies, controlling cytokine production and inflammatory response is a promising field.

Orthotopic neobladder after cystectomy for bladder cancer.

More than 90% of bladder cancer is composed of transitional cell carcinoma (TCC), being characterized by the development of multiple tumors in the entire urinary tract over time. When cystectomy is conducted, the urinary tract must be reconstructed by various procedures, which can include an orthotopic neobladder using the patient's own intestine formed into a spherical shape anastomosed to the urethra. Using this procedure, patients can void urine from their own urethra even after cystectomy. The incidence of subsequent urethral cancer arising after cystectomy is known to be relatively high; however, if patients with a high risk of urethral recurrence are appropriately excluded, a neobladder can be safely provided for patients. Orthotopic neobladder use is reviewed from an oncological viewpoint and the patient's quality of life after cystectomy for bladder cancer.

RAB14 activates MAPK signaling to promote bladder tumorigenesis.

Bladder cancer (BC) is a fatal invasive malignancy accounting for approximately 5% of all cancer deaths in humans; however, the underlying molecular mechanisms and potential targeted therapeutics for BC patients remain unclear. We report herein that RAB14 was overexpressed in BC tissues and cells with high metastatic potential and its abundance was significantly associated with lymph node metastasis (P = 0.001), a high-grade tumor stage (P = 0.009), poor differentiation (P < 0.001) and unfavorable prognoses of BC patients (P = 0.003, log-rank test). Interference by RAB14 mediated a reduction in the TWIST1 protein and inhibited cell migration and invasion (P < 0.05). Moreover, silencing RAB14 reduced cell proliferation and induced apoptosis in vitro and suppressed tumorigenesis in a mouse xenograft model. We demonstrated that RAB14-promoted BC cancer development and progression were associated with activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase signaling through upregulation of MAPK1/MAPK8 and downregulation of dual-specificity protein phosphatase 6/Src homology 2 domain containing transforming protein/Fos proto-oncogene, AP-1 transcription factor subunit (FOS). We provide evidence that RAB14 acts as a tumor promoter and modulates the invasion and metastatic potential of BC cells via activating the MAPK pathway.

Estimating Minimally Important Differences for the Bladder Cancer Index Using Distribution and Anchor Based Approaches.

PURPOSE: The BCI (Bladder Cancer Index) is a validated, condition specific health questionnaire assessing urinary, bowel and sexual function and quality of life among patients with bladder cancer. We aimed to establish minimally important difference score thresholds that signal clinical importance. MATERIALS AND METHODS: For 1 year after surgery we followed a prospective cohort of 150 patients who underwent radical cystectomy between 2013 and 2016. Usable data on 138 patients were analyzed. The BCI and the Medical Outcomes Study SF-36 (36-Item Short Form Health Survey) questionnaires were completed prior to cystectomy, and 3, 6 and 12 months postoperatively. Distribution based, minimally important differences were estimated at ⅓ and ½ SD for each index domain across time points. Changes in index domain scores anchored to changes in a SF-36 overall health assessment question were used to estimate anchor based, minimally important differences. Pooled averages are reported between time points and methods. RESULTS: The distribution based, minimally important difference of ⅓ SDs for urinary, bowel and sexual domains ranged between 5.3 and 7.3, 4.6 and 5.6, and 6.0 and 8.9 points, respectively. Ranges of ½ SDs were 8.8 and 10.9, 6.8 and 8.4, and 8.9 and 13.5 points, respectively. The anchor based approach resulted in minimally important difference estimates of 6.2, 7.3 and 6.8 points, respectively. Aggregated results across the 2 approaches resulted in minimally important differences of 6 to 9, 5 to 8 and 7 to 11 points for urinary, bowel and sexual domains, respectively. CONCLUSIONS: Using 2 independent approaches to our knowledge we established the first minimally important difference estimates for the BCI. Defining patient reported outcome thresholds is important to interpret changes or differences in BCI scores.

Fatty acid oxidation inhibitor etomoxir suppresses tumor progression and induces cell cycle arrest via PPARγ-mediated pathway in bladder cancer.

Tumor cells rely on aerobic glycolysis as their main energy resource (Warburg effect). Recent research has highlighted the importance of lipid metabolism in tumor progression, and certain cancers even turn to fatty acids as the main fuel. Related studies have identified alterations of fatty acid metabolism in human bladder cancer (BCa). Our microarray analysis showed that fatty acid metabolism was activated in BCa compared with normal bladder. The free fatty acid (FFA) level was also increased in BCa compared with paracancerous tissues. Inhibition of fatty acid oxidation (FAO) with etomoxir caused lipid accumulation, decreased adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide phosphate (NADPH) levels, suppressed BCa cell growth in vitro and in vivo, and reduced motility of BCa cells via affecting epithelial-mesenchymal transition (EMT)-related proteins. Furthermore, etomoxir induced BCa cell cycle arrest at G0/G1 phase through peroxisome proliferator-activated receptor (PPAR) γ-mediated pathway with alterations in fatty acid metabolism associated gene expression. The cell cycle arrest could be reversed by PPARγ antagonist GW9662. Taken together, our results suggest that inhibition of FAO with etomoxir may provide a novel avenue to investigate new therapeutic approaches to human BCa.

SEC11A Expression Is Associated with Basal-Like Bladder Cancer and Predicts Patient Survival.

OBJECTIVES: Bladder cancer (BC) is a common malignancy worldwide. Signal peptidase complex 18 (SPC18) protein, which is encoded by the SEC11A gene, is one of the subunits of the signal peptidase complex and induces transforming growth factor-α secretion. In the present study, we analyzed the expression and function of SPC18 protein in human BC. METHODS: Expression of SPC18 was analyzed by immunohistochemistry. RNA interference was used to inhibit SEC11A expression in BC cell lines. For constitutive expression of the SEC11A gene, a SEC11A expression vector was transfected into BC cell lines. To examine cell viability, we performed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Modified Boyden chamber assays were used to examine cell invasiveness. RESULTS: SPC18 was upregulated in 54% of 81 BC cases. SPC18 expression served as an independent prognostic classifier of patients with BC. SPC18-positive BC cases frequently expressed cytokeratin 5/6, a marker of basal-like BC. Cell growth and invasiveness were inhibited by SEC11A knockdown and enhanced by forced expression of SEC11A. CONCLUSION: These results indicate that SPC18 plays an important role in the progression of BC. Specific inhibitors of SPC18 may be promising anticancer drugs for patients with basal-like BC.

Treatment Approaches for Cisplatin-Ineligible Patients with Invasive Bladder Cancer.

OPINION STATEMENT: Cisplatin has been established as an important agent in the neoadjuvant setting prior to radical cystectomy (RC) surgery for muscle-invasive urothelial cancer (MIUC) as well as in the unresectable or metastatic urothelial carcinoma (mUC) setting. Unfortunately, many patients in practice are felt to be "cisplatin-ineligible." Thus, it is vital that we develop treatment approaches and novel therapeutics for this population. We evaluate therapeutic alternatives to cisplatin-based treatment. For patients undergoing RC, there is no recommended alternative to neoadjuvant cisplatin-based combination therapy, and upfront RC or clinical trials are preferable. For patients receiving "bladder-sparing" radiation, concurrent radiosensitizing chemotherapies may be used, and several trials are also underway. For cisplatin-ineligible patients with mUC who are eligible for chemotherapy, carboplatin-based or split-dose cisplatin-based regimens may be employed. Pembrolizumab and atezolizumab offer options as first-line therapy for cisplatin-ineligible patients with high PD-L1 expression. The results of trials combining checkpoint inhibitors or platinum-based chemotherapy plus PD1/PD-L1 inhibitors are eagerly awaited. For platinum or chemotherapy-ineligible patients with mUC, immune checkpoint inhibitors such as inhibitors of programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) are approved regardless of PD-L1 expression. However, given limited effectiveness of first-line PD-1/PD-L1 inhibitor monotherapy in tumors with low PD-L1 expression, trials in this space are critical.

MicroRNA-98 promotes drug resistance and regulates mitochondrial dynamics by targeting LASS2 in bladder cancer cells.

MicroRNA-98(miR-98) has been shown to be critical for tumorigenesis, however its involvement in bladder cancer are unclear. The present study aims to investigate the expression, biological roles and potential mechanisms of miR-98 in human bladder cancer. We found that miR-98 was upregulated in bladder urothelial carcinoma tissues compared with adjacent normal tissues. In addition, miR-98 expression was higher in bladder cancer cell lines than in uroepithelial cell line SV-HUC-1. Functional studies revealed that miR-98 mimic promoted proliferation of T24 cells while miR-98 inhibitor inhibited proliferation of BIU-87 cells. Moreover, miR-98 mimic increased cisplatin/doxorubicin resistance and inhibited apoptosis in T24 cells, while miR-98 inhibitor decreased chemoresistance and facilitated apoptosis in BIU-87 cells. Further experiments using MitoTracker and JC-1 staining showed that miR-98 could regulate mitochondrial fission/fusion balance and mitochondrial membrane potential. Western blot showed that miR-98 upregulated cyclin D1, p-Drp1 and Drp1. Using luciferase reporter assay, we demonstrated that LASS2 acted as a direct target of miR-98. LASS2 overexpression induced mitochondrial fusion and downregulated mitochondrial potential, with decreased p-Drp1 status. Additionally, LASS2 siRNA abrogated the effects of miR-98 mimic on Drp1phosphorylation and chemoresistance. We also found a negative correlation between LASS2 and miR-98 in bladder cancer tissues. In conclusion, our study demonstrates that miR-98 targets LASS2 and regulates bladder cancer chemoresistance through modulation of mitochondrial function.

Zonula occludens-1 associated nucleic acid binding protein plays an invasion-promoting role in bladder cancer.

Cancer cell invasion is an important characteristic of malignant tumors. Cancer cells overcome the constraints of tight junctions (TJ) to invade other tissues, but less is known about the regulating role of tight junction on bladder cancer (BC) invasion. In order to identify the invasion-regulating function of tight junction component, we investigated the oncogenetic features of zonula occludens-1 associated nucleic acid binding protein (ZONAB), a TJ protein that is usually highly expressed in solid cancers. Expression of ZONAB was found to be up-regulated in human BC cell lines detected by real-time PCR, Western blotting. ZONAB expression was significantly up-regulated in BC cell lines and negatively regulated E-cadherin expression. Overexpression of ZONAB by stable transduction in human BC cell lines promoted invasion detected by transwell invasion assay. Conversely, stable suppression of ZONAB expression by RNA interference (RNAi) in BC cells attenuated invasion. A similar role for ZONAB in promoting invasion and EMT was observed in xenografts. In summary, ZONAB is up-regulated in BC cell lines, which promotes invasion, demonstrating the important role it plays in tumorogenesis and cancer progression.

Preparation of allyl isothiocyanate nanoparticles, their anti-inflammatory activity towards RAW 264.7 macrophage cells and anti-proliferative effect on HT1376 bladder cancer cells.

BACKGROUND: Allyl isothiocyanate (AITC), a volatile and water-insoluble compound present in several cruciferous vegetables, has been shown to possess several biological qualities such as anti-bacterial, anti-fungal, and anti-cancer activity. In this study, water-soluble allyl isothiocyanate nanoparticles (AITC-NPs) were prepared by oil dispersed in water (O/W) microemulsion and complex coacervation techniques and evaluated for their anti-inflammatory activity towards macrophage cell RAW 264.7 and anti-cancer effect on human bladder cancer cell HT1376. RESULTS: The AITC-NPs with a particle size of 9.4 nm were stable during heating up to 110 °C or three freeze-thawing cycles. No significant cytotoxicity was shown on Caco-2 and intestine epithelial IEC-6 cells at AITC-NP doses ranging from 0.25 to 2 g L-1 (8.75-70 mg L-1 AITC). However, at 2 g L-1 dosage, AITC-NPs could inhibit the growth of human bladder cancer cells HT1376 by 90%, while their low dosage at 0.25 g L-1 could inhibit migration ability by 83.7, 71.3, 58.4 and 31.4% after 4, 8, 12, and 24 h of incubation, respectively. Compared to AITC and NPs, AITC-NPs showed a better inhibition on lipopolysaccharide (LPS)-induced TNF-α, IL-6, NO and iNOS production in RAW 264.7 macrophage cells. CONCLUSION: The results demonstrate the potential of AITC-NPs as therapeutic agents for the treatment of bladder cancer and the enhancement of immune function. © 2018 Society of Chemical Industry.

Decrease in skeletal muscle index 1 year after radical cystectomy as a prognostic indicator in patients with urothelial bladder cancer.

PURPOSE: The present study aimed to determine whether sarcopenia after radical cystectomy (RC) could predict overall survival (OS) in patients with urothelial bladder cancer (UBC). MATERIALS AND METHODS: The lumbar skeletal muscle index (SMI) of 80 patients was measured before and 1 year after RC. The prognostic signifi cance of sarcopenia and SMI decrease after RC were evaluated using Kaplan-Meier analysis and a multivariable Cox regression model. RESULTS: Of 80 patients, 26 (32.5%) experienced sarcopenia before RC, whereas 40 (50.0%) experienced sarcopenia after RC. The median SMI change was -2.2 cm2/m2. Patients with sarcopenia after RC had a higher pathological T stage and tumor grade than patients without sarcopenia. Furthermore, the overall mortality rate was signifi - cantly higher in patients with sarcopenia than in those without sarcopenia 1 year after RC. The median follow-up time was 46.2 months, during which 22 patients died. Kaplan-Meier estimates showed a signifi cant difference in OS rates based on sarcopenia (P=0.012) and SMI decrease (P=0.025). Multivariable Cox regression analysis showed that SMI decrease (≥2.2 cm2/m2) was an independent predictor of OS (hazard ratio: 2.68, confi dence interval: 1.007-7.719, P = 0.048). CONCLUSIONS: The decrease in SMI after surgery might be a negative prognostic factor for OS in patients who underwent RC to treat UBC.