Transitional Cell Carcinoma Of Bladder Research Articles

Blockade of the STAT3/BCL-xL Axis Leads to the Cytotoxic and Cisplatin-Sensitizing Effects of Fucoxanthin, a Marine-Derived Carotenoid, on Human Bladder Urothelial Carcinoma Cells

Bladder cancer is a globally prevalent urological malignancy, with transitional carcinoma (TCC) representing the majority of cases. Cisplatin is the primary drug for metastatic bladder cancer chemotherapy; however, its application is limited by nephrotoxicity and resistance. Signal Transducer and Activator of Transcription 3 (STAT3) is an oncogenic transcription factor often overactivated in various cancers, making it an appealing drug target. Fucoxanthin, a marine carotenoid, has significant anticancer properties. This study explored Fucoxanthin’s cytotoxic effects and its potential to potentiate the efficacy of Cisplatin, along with the mechanisms underlying these effects, on human bladder TCC cells. We demonstrated that Fucoxanthin is cytotoxic to bladder TCC cells by inducing apoptosis, evidenced by z-VAD-fmk-mediated annulment of Fucoxanthin’s cytotoxicity. Furthermore, Fucoxanthin reduced the levels of inherent or interleukin-6-induced tyrosine 705-phosphorylated STAT3 accompanied by downregulating BCL-xL, a well-established STAT3 target. Notably, ectopic expression of STAT3-C, a dominant-active STAT3 mutant, or BCL-xL thwarted Fucoxanthin’s proapoptotic and cytotoxic actions. Moreover, Fucoxanthin at subtoxic dosages enhanced the susceptibility to Cisplatin-induced apoptosis of bladder TCC cells initially resistant to Cisplatin. Remarkably, this Cisplatin-sensitizing effect of Fucoxanthin was abrogated when cells ectopically expressed STAT3-C or BCL-xL. Overall, for the first time, we proved that the proapoptotic, cytotoxic, and Cisplatin-sensitizing effects of Fucoxanthin on human bladder TCC cells are attributed to the blockade of the STAT3/BCL-xL axis. Our findings highlight that targeting the STAT3/BCL-xL axis is a promising strategy to eliminate bladder TCC cells and facilitate Cisplatin sensitization, and further support the potential of incorporating Fucoxanthin into Cisplatin-based chemotherapy for treating bladder cancer.

Evolutionary trajectories of immune escape across cancers.

Immune escape is a critical hallmark of cancer progression and underlies resistance to multiple immunotherapies. However, it remains unclear when the genetic events associated with immune escape occur during cancer development. Here, we integrate functional genomics studies of immunomodulatory genes with a tumor evolution reconstruction approach to infer the evolution of immune escape across 38 cancer types from the Pan-Cancer Analysis of Whole Genomes dataset. Different cancers favor mutations in different immunomodulatory pathways. For example, the antigen presentation machinery is highly mutated in colorectal adenocarcinoma, lung squamous cell carcinoma, and chromophobe renal cell carcinoma, and the protein methylation pathway is highly mutated in bladder transitional cell carcinoma and lung adenocarcinoma. We also observe different timing patterns in multiple immunomodulatory pathways. For instance, mutations impacting genes involved in cellular amino acid metabolism were more likely to happen late in pancreatic adenocarcinoma. Mutations in the glucocorticoid receptor regulatory network pathway tended to occur early, while mutations in the TNF pathways were more likely to occur late in B-cell non-Hodgkin lymphoma. Mutations in the NOD1/2 signaling pathway and DNA binding transcription factor activity tended to happen late in breast adenocarcinoma and ovarian adenocarcinoma. Together, these results delineate the evolutionary trajectories of immune escape in different cancer types and highlight opportunities for improved immunotherapy of cancer.

Development and Validation of a Competitive Risk Model in Elderly Patients with Transitional Cell Bladder Carcinoma.

BACKGROUND Transitional cell bladder carcinoma (tcBC) is the predominant form of bladder cancer, making up around 95% of reported cases. Prognostic factors for older individuals with tcBC differ from those affecting younger patients. The main purpose of this study was to establish a prognostic competing risk model for elderly patients with tcBC. MATERIAL AND METHODS We conducted a retrospective analysis using data from the SEER database, randomly assigning patients to training and validation groups. We applied proportional subdistribution hazard (SH) to assess risk factors for cancer-related mortality (CSM). A competitive risk model was created to predict cancer-specific survival in elderly patients with tcBC. Model validation involved evaluating the area under the receiver operating curve, the consistency index, and a calibration curve. The Kaplan-Meier (K-M) curve was then used to compare mortality risk between high-risk and low-risk groups identified by the model. RESULTS This study randomly assigned 61 293 patients from the SEER database into training (42 905 patients) and validation (18 388 patients) groups in a 7: 3 ratio. Using a proportional subdistribution hazards model, we identified prognostic risk factors such as age, race, sex, marital status, TNM staging, grade, and metastatic status in brain, bone, liver, and lung. We developed a competitive risk model to predict 5-year cancer-specific survival (CSS) in elderly tcBC patients, achieving consistency index (C-index) values of 0.814 and 0.815 for the training and validation groups, respectively. Kaplan-Meier (K-M) analysis revealed 5-year survival probabilities of 35.1% (high-risk) and 42.2% (low-risk) in the training group, with similar rates of 35.7% and 42.0% in the validation group, both showing statistically significant differences (log-rank P<0.01). CONCLUSIONS We successfully established a competitive risk model for forecasting cancer-specific survival in elderly tcBC patients, primarily relying on these identified risk factors. The validation outcomes indicate the model's accuracy and dependability, making it a highly efficient predictive instrument. This tool enables making personalized clinical decisions for both medical professionals and patients.

Cryptotanshinone Suppresses the STAT3/BCL-2 Pathway to Provoke Human Bladder Urothelial Carcinoma Cell Death.

Bladder cancer is one of the most common human malignancies worldwide. Aberrant activation of signal transducer and activator of transcription 3 (STAT3) is crucial to driving malignant progression and predicting poor prognosis of multiple human cancers, including bladder cancer, making STAT3 a promising target of cancer therapeutics. Cryptotanshinone (CTS) is an anticancer ingredient of Danshen (Salvia miltiorrhiza), a top-graded Chinese medicinal herb. However, whether CTS targets STAT3 to exert its cytotoxic effect on human bladder cancer remains unknown. Herein, we demonstrated that CTS is cytotoxic to multiple human urinary bladder transitional cell carcinoma (TCC) cell lines while sparing normal human urothelial cells. CTS provoked apoptosis-dependent bladder TCC cytotoxicity, as apoptosis blockage by z-VAD-fmk markedly rescued the clonogenicity of CTS-treated cells. Besides, CTS was found to suppress constitutive and interleukin 6-inducible activation of STAT3, evidenced by the downregulation of STAT3 tyrosine 705 phosphorylation and BCL2, a recognized STAT3 transcriptional target. Notably, ectopic expression of a dominant-active STAT3 mutant (STAT3-C) or BCL-2 alleviated CTS-induced apoptosis and clonogenicity inhibition, thus confirming STAT3 blockade as a pivotal mechanism of CTS's cytotoxic action on bladder TCC cells. Lastly, immunoblotting revealed that CTS lowered the levels of active JAK2, an upstream kinase that mediates STAT3 tyrosine 705 phosphorylation. Altogether, we conclude that the blockade of the JAK2/STAT3/BCL-2 antiapoptotic signaling axis is a vital mechanism whereby CTS provokes bladder cancer cytotoxicity. The current evidence implicates CTS's potential to be translated into a bladder cancer therapeutic agent.

Predictive Value of E-Cadherin, β-Catenin and SOX4 in Recurrence and/or Progression of Non-Muscle Invasive Urinary Bladder Transitional Cell Carcinoma. A Retrospective Study

Abstract Background Bladder cancer (BC) is one of the most common genitourinary cancers worldwide, the pathophysiology and etiology of BC are complicated, including both internal genetic and environmental factors. Currently, some studies suggest that the abnormal function of intercellular adhesion molecules is highly correlated with the invasion of surrounding tissues and distant organ metastasis of BC. Objective To develop a correlation between these markers and NMIBC and to help predict the recurrence and/or progression. Patients and Methods It is a retrospective cohort (observational) study assessing a correlation regarding the alternation in the expression of E-cadherin, β-catenin and SOX4 in determining the recurrence and/or progression and their prognostic value in NMIBC TCC. Patients Diagnosed with NMIBC TCC and their follow ups data were evaluated at the urology department in Theodor Bilharz Research Institute (TBRI) and Ain Shams University from January 2019 – till July 2022. Results Loss of normal expression of E-cadherin and β-catenin, upregulation of SOX4 is significantly correlated with BC and tumorigenesis, yet no clear relation between E-cadherin, β- catenin and SOX4 in progression or recurrence of NMIBC, regarding It’s staining intensity, percentage of positive cells and immunoreactive score (IRS). Conclusion bases on our current study, E-cadherin, β-catenin and SOX4 showed highly significance difference between normal urothelium and TCC NMIBC indicating it may have a role in diagnosis, although its value changes with follow up of the patients but of non-significant difference to predict prognosis, recurrence and/or progression among TCC NMIBC.

Bladder transitional cell carcinoma anatomic primary site as a predictor of survival and mortality: a population-based retrospective cohort study

Background: Bladder cancer is a heterogeneous disease with varying prognostic outcomes based on the primary tumor site within the bladder. This study aims to evaluate the impact of tumor location on overall survival and cancer-specific survival in bladder cancer patients. Methods: The authors conducted a retrospective cohort study using data from the Surveillance, Epidemiology, and End Results database. Patients with primary transitional cell carcinoma of the bladder were categorized based on their tumor locations. Survival outcomes were assessed using Kaplan–Meier analysis and Cox proportional hazards regression models, adjusted for age, sex, race, cancer stage, and treatment modalities. Additionally, binary logistic regression models were employed to predict overall mortality (OM) and cancer-specific mortality (CSM) at 1, 5, and 10 years. Results: The study included 107 909 patients diagnosed with primary bladder cancer between 2000 and 2021. Significant differences in survival outcomes were observed across different tumor sites. Bladder cancer originating in the urachus had the worst OS before 100 months and the worst CSS overall. Tumors in the anterior wall showed the worst OS after 100 months. In the Cox multivariable analysis, anterior wall tumors were associated with a 1.513-fold increased risk of death compared to lateral wall tumors. The binary logistic regression models showed that anterior wall tumors predicted the highest OM and CSM at 1-year, while urachal tumors had the worst outcomes at 5 and 10 years. Conclusions: The primary site of bladder cancer is a significant predictor of survival outcomes, with tumors in the urachus and anterior wall associated with a poorer prognosis. These findings underscore the importance of considering tumor location in the prognosis and management of bladder cancer. Future studies should aim to validate these findings in more diverse populations and explore the underlying biological mechanisms that drive these differences.

Hotspot Exon 15 Mutations in BRAF Are Uncommon in Feline Tumours.

BRAF is one of multiple RAF proteins responsible for the activation of the MAPK cell signalling cascade involved in cell growth, differentiation, and survival. A hotspot BRAFV600E mutation, in exon 15, was determined to be a driver in 100% hairy cell leukaemias, 50%-60% of human melanomas, 30%-50% of human thyroid carcinomas and 10%-20% of human colorectal carcinomas. The orthologous BRAFV595E mutation was seen in 67% and 80% of canine bladder transitional cell carcinomas and prostatic adenocarcinomas, respectively. Since veterinary and human cancers exploit similar pathways and BRAF is highly conserved across species, BRAF can be expected to be a driver in a feline cancer. Primers were developed to amplify exon 15 of feline BRAF. One hundred ninety-six feline tumours were analysed. Sanger sequencing of the 211 bp PCR amplicon was done. A BRAF mutation was found in one tumour, a cutaneous melanoma. The mutation was a BRAFV597E mutation, orthologous to the canine and human hotspot mutations. A common synonymous variant, BRAFT586T, was seen in 23% (47/196) of tumours. This variant was suspected to be a single nucleotide polymorphism. BRAF was not frequently mutated in common feline tumours or in tumour types that frequently harbour BRAF mutations in human and canine cancers. As is seen in canine cancer genomics, the mutational profile in feline tumours may not parallel the histologic equivalent in human oncology.

Possible adverse events of imidazole antifungal drugs during treatment of vulvovaginal candidiasis: analysis of the FDA Adverse Event Reporting System

Azole antifungal drugs are commonly used to treat vulvovaginal candidiasis (VVC). The nephrotoxicity and developmental toxicity of azole drugs have not been systematically analyzed in the real world. We used the FDA Adverse Event Reporting System (FAERS) to investigate the adverse events (AEs) associated with imidazole therapy for VVC. FAERS data (from quarter 1 2004 to quarter 3 2022) were retrieved using OpenVigil 2.1, and AEs were retrieved and standardized according to the Medical Dictionary for Regulatory Activities (MedDRA). In the top 10 System Organ Class (SOC), all four drugs have been found to have kidney and urinary system diseases and pregnancy. We found significant signals, including clotrimazole [bladder transitional cell carcinoma, (report odds ratio, ROR = 291.66)], [fetal death, (ROR = 10.28)], ketoconazole[nephrogenic anemia (ROR = 22.1)], [premature rupture of membranes (ROR = 22.91 46.45, 11, 3)], Miconazole[hematuria (ROR = 19.03)], [neonatal sepsis (ROR = 123.71)], [spontaneous abortion (ROR = 5.98)], Econazole [acute kidney injury (ROR = 4.41)], [spontaneous abortion (ROR = 19.62)]. We also discovered new adverse reactions that were not reported. Therefore, when using imidazole drugs for treatment, it is necessary to closely monitor the patient's renal function, pay attention to the developmental toxicity of the fetus during pregnancy, and be aware of potential adverse reactions that may occur.

A phase I/II, first-in-human study of VLS-1488, an oral KIF18A inhibitor, in patients with advanced cancer.

TPS3181 Background: Chromosomal instability (CIN) is a hallmark of cancer characterized by high rates of chromosomal segregation errors during mitosis. This creates structural and numerical changes to chromosomes, driving genetic heterogeneity and cancer evolution. KIF18A is a mitotic kinesin protein shown to be important for successful division of cancer cells with CIN but not required for mitosis in normal diploid cells. Pre-clinical studies demonstrated that treatment of chromosomally unstable cancer cells in vitro and in xenograft models (HCC15 and OVCAR-3) with a KIF18A inhibitor resulted in failure of chromosomal congression, mitotic arrest, cell death and dose-dependent inhibition of tumor growth. VLS-1488 is an oral small molecule inhibitor of KIF18A that is being examined in an open-label, phase I/II, first-in-human study evaluating the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity in advanced solid tumors with high prevalence of CIN. Methods: Key eligibility criteria include specific histologically confirmed metastatic or advanced tumor types with at least one site of measurable disease per RECIST 1.1, adequate organ function, and mismatch repair proficient/microsatellite stable.Eligible tumor types include high grade serous ovarian/fallopian tube/primary peritoneal cancer, squamous non-small cell lung cancer, triple negative breast cancer, gastric adenocarcinoma, gastroesophageal cancer, esophageal cancer, colorectal adenocarcinoma, transitional cell carcinoma of bladder, head and neck squamous cell carcinoma, ovarian or uterine carcinosarcoma, and uterine serous carcinoma. Subjects will receive VLS-1488 monotherapy continuously for 28-day cycles once daily. The study consists of two parts, Dose Escalation and Dose Expansion. Utilizing a Bayesian Optimal Interval (BOIN) design, Dose Escalation will examine the safety and tolerability of VLS-1488 at various dose levels (DLs) to identify the Maximum Tolerated Dose (MTD) and to select DLs for Dose Expansion. Dose Expansion may commence after the MTD or DLs of interest are identified. Dose Expansion will examine the safety, tolerability, preliminary efficacy and preliminary drug-drug interaction (DDI) and food effect risk of VLS-1488 in selected tumor types. Subjects enrolled to specific tumor type cohorts may be randomized to DLs of interest. Enrollment to Dose Escalation began in September 2023 and is ongoing. Clinical trial information: NCT05902988 .

Long term outcomes and impact on renal function following radical cystectomy.

To assess clinical, oncological outcomes and impact on renal function in patients who underwent the radical cystectomy with pelvic lymphadenectomy for muscle invasive and high risk non-muscle invasive transitional cell carcinoma of urinary bladder without evidence of non-regional lymph nodes and distant metastasis. With curative intent total 156 patients underwent radical cystectomy with pelvic lymphadenectomy from January 2015 to December 2022. Total 132/156 patients had primary transitional cell carcinoma of bladder. Thirty patients, presented with obstructive nephropathy, operated after stabilization of renal function. Pre-operatively and post-operatively eGFR calculated using modified diet in renal disease formula. In present study 114 (86.36%) patients had high grade TCC, 70 (53.02%) patients had organ confined disease. Nodal extension seen in 74 (56.06%) patients. Perioperative mortality noted in 36 (27.2%) patients. The overall survival and recurrence free survival (RFS) over 5 years was 66.67 and 45.45%. RFS was significantly related to pathological stage, nodal status, histological-grade, positivity of surgical margin and time of surgery from diagnosis. Total 92/132 (69.7%) patients had recurrence. Pelvic recurrence in 10/92 (10.87%) whereas 82/92 (89.13%) patients had distant recurrence. Pre-operatively mean creatinine was 2.6 mg/dl and mean eGFR was 38.9 ml/h in patients who presented with obstructive nephropathy after stabilization of renal function. Post-operatively in 46/132 (34.8%) patients had improvement in eGFR while 86/132 (65.2%) patients had deterioration of eGFR over 62 months of median follow up. Radical cystectomy provides good overall survival outcomes. Pre-operative eGFR has significant impact on post-operative renal function in long term.

A case of canine bladder transitional cell carcinoma treated with urethrocystectomy followed by total vaginectomy

A case of canine bladder transitional cell carcinoma treated with urethrocystectomy followed by total vaginectomy

Nuclear morphometry and expression of CK20, p53 and Ki-67 in the diagnosis of bladder transitional cell carcinomas in dogs

Nuclear morphometry and expression of CK20, p53 and Ki-67 in the diagnosis of bladder transitional cell carcinomas in dogs

Radiation toxicity grading after chemoradiotherapy of canine urinary tract carcinomas: Comparing VRTOG to VRTOG_v2.0.

Radiation toxicities may be underestimated after treatment of transitional cell carcinoma in dogs' lower urinary tract. Assessing acute and late toxicities and differentiating them from progressive disease (PD) impacts further therapeutic approach. We retrospectively assessed dogs treated with definitive-intent chemoradiotherapy (12 × 3.8 Gy, various first-line chemotherapeutics). Local tumour control, radiation toxicities and survival were evaluated. We classified radiation toxicities according to the previously published radiation toxicity scheme "VRTOG" as well as the updated version, "VRTOG_v2.0". Fourteen dogs with transitional cell carcinoma of bladder ± urethra (n = 8), +prostate (n = 3) or solely urethra (n = 3), were included. Median follow-up was 298 days (range 185-1798 days), median overall survival 305 days (95%CI = 209;402) and 28.6% deaths were tumour-progression-related. Acute radiation toxicity was mild and self-limiting with both classification systems: In VRTOG, 5 dogs showed grade 1, and 1 dog grade 2 toxicity. In VRTOG_v2.0, 2 dogs showed grade 1, 3 dogs grade 2, and 3 dogs grade 3 toxicity. Late toxicity was noted in 14.2% of dogs (2/14) with the VRTOG, both with grade 3 toxicity. With VRTOG_v2.0, a larger proportion of 42.9% of dogs (6/14) showed late toxicities: Four dogs grade 3 (persistent incontinence), 2 dogs grade 5 (urethral obstructions without PD resulting in euthanasia). At time of death, 5 dogs underwent further workup and only 3 were confirmed to have PD. With the updated VRTOG_v2.0 classification system, more dogs with probable late toxicity are registered, but it is ultimately difficult to distinguish these from disease progression as restaging remains to be the most robust determinant.

A rare case of cutaneous metastasis of bladder transitional cell carcinoma

Introduction: The cutaneous metastasis of bladder transitional cell carcinoma (TCC) is uncommon. The number of publications describing this entity is sparse. The cutaneous metastasis manifestation may occur at the time of diagnosis or appear months to years after the diagnosis of bladder TCC. Case description: A 61-year-old male patient presented with a palpable lump in the right lower back that felt for two months before visiting the urology outpatient clinic for routine postoperative follow-up after radical cystectomy one year before. The patient underwent tumor excision, and the pathological analysis supports the diagnosis of metastatic bladder transitional cell carcinoma. The patient then underwent chemotherapy using the gemcitabine-cisplatin protocol. Two years after the cutaneous lesion was diagnosed, the patient is currently surviving. Conclusion: Cutaneous metastasis of the bladder TCC is a rare disease condition where possible diagnostic difficulties may occur, and a specific treatment protocol is also yet to be defined. In patients with a previous history of bladder cancer with cutaneous lesions, metastatic disease must be considered in the differential diagnosis.

Assessment of Tumor-Associated Tissue Eosinophilia (TATE) and Tumor-Associated Macrophages (TAMs) in Canine Transitional Cell Carcinoma of the Urinary Bladder

Transitional cell carcinoma of the urinary bladder is a significant neoplasm in dogs, characterized by a poor prognosis and a high metastatic potential. These canine spontaneous tumors share many characteristics with human transitional cell carcinoma, making them an excellent comparative model. The role of inflammatory infiltration in tumor development and progression is frequently contradictory, especially concerning tumor-associated tissue eosinophils (TATE) and tumor-associated macrophages (TAMs). This study aims to analyze TATE and TAMs in canine transitional cell carcinoma of the urinary bladder. Congo Red staining was used to identify TATE, and immunohistochemistry was performed to detect TAMs in 34 cases of canine transitional cell carcinoma of the bladder carcinomas, categorized into low and high grades. Statistically significant differences were observed between the number of eosinophils and macrophages in the two groups of tumors. The number of TATE was higher in low-grade malignant tumors, but the number of TAMs was higher in high-grade tumors. Our findings suggest the importance of TATEs and TAMs in the aggressiveness of canine transitional cell carcinoma and propose their potential use as therapeutic targets.

Downregulation of the keratins CK13 and CK14 does not significantly affect cell viability of human urinary bladder carcinoma cells.

Bladder cancer is the ninth most common tumour entity worldwide. Aberrant expression of different keratins has been described in bladder cancer, which is used for diagnostic purposes, but it can also have prognostic value. However, not all keratins have been analysed in bladder cancer, and whether keratins are important for cell viability of bladder cancer tumour cells is not yet known. We analyse the expression of CK10, CK13, and CK14 in 4 different urinary bladder transitional cell carcinoma cell lines via western blot. Furthermore, we downregulate the expression of CK13 and CK14 using siRNAs and evaluate the cell viability of the carcinoma cells. In this study, we show that different urinary bladder transitional cell carcinoma cell lines have distinct expression pattern of the keratins CK10, CK13, and CK14. Using several siRNAs targeting either CK13 or CK14, we show that both keratins have long protein half-lives. Although we achieve a reduction in CK13 and CK14 protein levels, these reductions do not influence the cell viability of the cell lines. In conclusion, we provide evidence that CK10, CK13, and CK14 are expressed on the protein level in different urinary bladder transitional cell carcinoma cell lines, but that their targeting does not affect the viability of the carcinoma cells.

Costello Syndrome and Transitional Cell Carcinoma of Bladder

Costello Syndrome and Transitional Cell Carcinoma of Bladder

Incidence, mortality and survival of transitional cell carcinoma in the urinary system: A population-based analysis.

The goal of this study is exploring the disparity of incidence, mortality and survival outcome among transitional cell carcinomas (TCCs) in the 4 parts of urinary system. This study comprehensively evaluates these disparities using the Surveillance, Epidemiology, and End Results (SEER) (2000-2018) database. According to the SEER database, the urinary tract is divided into 4 parts: urinary bladder, renal pelvis, ureter, and urethra. The joinpoint regression was used to analyze the secular trend of incidence and incidence-based mortality (IBM). The Kaplan-Meier method with the log-rank test is performed to evaluate survival outcomes. The bladder TCC has the highest age-adjusted incidence and mortality rate compared with TCC in other 3 locations. A slight decrease in incidence is shown in the both bladder and urethra TCCs during 2000-2018. The age-adjusted mortality rate similarly presents an initial increase among 4 locations TCCs at the beginning of study period. The survival curves demonstrate that patients with bladder TCCs have better overall survival (OS) and cancer-specific survival (CSS), whereas those with renal pelvis TCCs have the worse OS and CSS. In addition, patients with bladder TCC have the highest 1-year, 3-year, 5-year relative survival rate, and those with renal pelvis TCC have the lowest. These disparities are especially essential when we explore tumor characteristics and treatment, extrapolated from the literature on bladder TCC for upper tract urothelial carcinoma (UTUC). Notably, patients with bladder TCC especially for localized stage have better survival outcomes than those with UTUC.

Anti-tumor activity of a recombinant measles virus against canine lung cancer cells

Canine primary lung cancer with metastasis has a poor prognosis with no effective treatment. We previously generated a recombinant measles virus (MV) that lost binding affinity to a principal receptor, SLAM, to eliminate its virulence as a new cancer treatment strategy. The virus, rMV-SLAMblind, targets nectin-4, recently listed as a tumor marker, and exerts antitumor activity against nectin-4-positive canine mammary cancer and urinary bladder transitional cell carcinoma cells. However, the effectivity of rMV-SLAMblind for other types of canine cancers is still unknown. Here we evaluated the antitumor effect of rMV-SLAMblind to canine lung cancer. Nectin-4 is expressed on three canine lung cancer cell lines (CLAC, AZACL1, AZACL2) and rMV-SLAMblind was able to infect these cell lines. CLAC cells showed reduced cell viability after virus infection. In the CLAC xenograft nude mouse model, intratumoral administration of rMV-SLAMblind significantly suppressed tumor growth. In rMV-SLAMblind-treated mice, natural killer cells were activated, and Cxcl10 and Il12a levels were significantly increased in comparison with levels in the control group. In addition, the depletion of NK cells reduced the anti-tumor effect. To understand difference in efficacy among canine lung cancer cell lines, we compared virus growth and gene expression pattern after virus treatment in the three canine lung cancer cell lines; virus growth was highest in CLAC cells compared with the other cell lines and the induction of interferon (IFN)-beta and IFN-stimulated genes was at lower levels in CLAC cells. These results suggested that rMV-SLAMblind exhibits oncolytic effect against some canine lung cancer cells and the cellular response after the virus infection may influence its efficacy.

Identification of hub genes in bladder transitional cell carcinoma through ceRNA network construction integrated with gene network analysis.

Bladder transitional cell carcinoma (BTCC) forms more than 90% of bladder cancer cases. It brings challenges to the early diagnosis and therapy of BTCC, due to lack of efficient screening biomarkers. We used weighted gene co-expression network analysis (WGCNA) combined competing endogenous RNA (ceRNA) network construction depending on TCGA datasets to investigate potential hub genes and regulatory pathways associated with occurrence and progression of BTCC. We further used real-time polymerase chain reaction (RT-PCR) to validate the relative expression genes correlated with BTCC. By WGCNA, the gene co-expression module with 11 genes was found corelated with BTCC tumour stage and prognosis after survival analyses. Ultimately, we put 100 highly stage-related genes into the above constructed ceRNA network and then constructed another new network. Among them, all elements in AC112721.1/LINC00473/AC128709.1-hsa-mir-195-RECK and LINC00460-hsa-mir-429-ZFPM2 axes were simultaneously corelated with overall survival. RT-PCR showed that AKAP12 was downregulated in tumour tissues. The hub genes screened out in the present study may provide ideals for further treatment on BTCC.