Epilepsy is a severe neurological disorder with complex pathogenesis. Mitochondrial dysfunction (MitD) is increasingly recognized as a key driver of epileptogenesis and seizure generation, contributing to neuronal hyperexcitability and network instability. However, the potential mechanisms linking MitD to epilepsy remain incompletely understood. This study aimed to identify MitD-related biomarkers in epilepsy and investigate their associations with alterations in the immune cell infiltration landscape during epileptogenesis. On the basis of the GSE47752 dataset, differential expression analysis was performed to identify differentially expressed genes (DEGs) between the control group and epilepsy groups in the early phase after status epilepticus (SE). The intersection of DEGs across time points yielded core DEGs, which were further intersected with MitD-related genes (MDRGs) to obtain MitD-related differentially expressed genes (MDR-DEGs). Multiple machine learning algorithms (LASSO, Boruta, XGBoost, and SVM-RFE) were applied to identify robust candidate biomarkers through consensus feature selection strategies, prioritizing genes with high stability across different algorithms. Importantly, immune infiltration was analyzed via the single-sample gene set enrichment analysis (ssGSEA) algorithm to characterize the immunological microenvironment in epilepsy. Finally, the expression of candidate biomarkers was validated via RT-qPCR in hippocampal tissues from a lithium-pilocarpine (Li-Pilo) rat model. Machine learning consensus pinpointed three candidate biomarkers: Idi1, Nubpl, and Tspo. Single-gene gene set enrichment analysis (GSEA) revealed that Nubpl and Tspo were significantly enriched in the complement and coagulation cascades pathway. Immune infiltration analysis revealed a substantial increase in the abundance of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs). The expression of Nubpl and Tspo was strongly positively correlated with that of most of these differentially infiltrated immune cell subsets. RT-qPCR confirmed that Nubpl and Tspo mRNA levels were significantly elevated in the early phase post-SE compared with those in controls, whereas the change in Idi1 expression was not statistically significant. Nubpl and Tspo were identified as key candidate biomarkers associated with MitD in epilepsy. The candidate biomarkers may contribute to epileptogenesis not only through direct mitochondrial pathways but also through crosstalk between complement and coagulation cascades and immune cell dynamics. These findings offer novel insights into the integrative molecular and immunological mechanisms linking MitD to epilepsy, highlighting potential therapeutic targets.

Most of pituitary adenomas are biologically benign, but some grow local-invasively and can invade important adjacent tissues, resulting in clinical symptoms such as hormone secretion disorders and visual field defects. MicroRNA-221/222 (miR-221/222) is tandemly encoded on the X chromosome in humans, mice and rats, and is highly conserved in vertebrates with the same seed sequence. To date, miR-221/222 has been reported as either a tumor suppressor or a tumor promoter in different tumors, however, its role in pituitary tumors has not been elucidated. Our study aimed to investigate the effect and mechanism of miRNA-221/222 in pituitary tumor cells. Results of real-time quantitative PCR showed that the expression level of miRNA-221/222 in plasma exosomes from patients with pituitary tumor was significantly higher than that from healthy people. Results of cell function experiments indicated that miRNA-221/222 significantly promoted cell proliferation and migration, inhibited apoptosis and significantly inhibited the expression of Cleaved-Caspase3 and E-cadherin, while promoted the expression level of N-cadherin. With transcriptome sequencing and comprehensive bioinformatics analysis, PHACTR4 was identified as the potential target gene of miRNA-221/222 in regulating biological functions of pituitary adenoma cells. Dual luciferase reporter assay confirmed that PHACTR4 was the direct target gene of miRNA-221/222 and overexpression of PHACTR4 gene reversed the regulatory effects of miRNA-221/222. In vivo experiment of subcutaneous tumor formation in nude mice verified that miRNA-221/222 promoted tumor growth by targeting PHACTR4. In conclusion, miRNA-221/222 played the role of proto-oncogene in the occurrence and development of pituitary tumors by targeting PHACTR4, which provided a new target for the diagnosis and molecular treatment of pituitary adenomas.

OBJECTIVE:We aim to study the MRI features of pituitary adenoma (PA) apoplexy and their relationship with hypoxia, proliferation, and pathology. METHODS:Sixty-seven patients with MRI signs of PA apoplexy were selected. According to the MRI signs, they were divided into the parenchymal group and the cystic group. The parenchymal group had a low signal area on T2WI without cyst >2 mm and this area was not significantly enhanced on the corresponding TW1 enhancement. The cystic group had a cyst >2 mm on T2WI, and the cyst showed liquid stratification on T2WI or high signal on T1WI. The relative T1WI (rT1WI) enhancement value and relative T2WI (rT2WI) value of non-apoplexy areas were measured. Protein levels of hypoxia-inducible factor-1 (HIF-1α), pyruvate dehydrogenase kinase 1 (PDK1), and Ki67 were detected with immunohistochemistry and Western blot. Nuclear morphology was observed with HE staining. RESULTS:The rT1WI enhancement average value, rT2WI average value, Ki67 protein expression level, and the number of abnormal nuclear morphology of non-apoplexy lesions in the parenchymal group were significantly lower than those in the cystic group. The protein expression levels of HIF-1α and PDK1 in the parenchymal group were significantly higher than those in the cystic group. HIF-1α protein was positively correlated with PDK1 but negatively correlated with Ki67. CONCLUSION:When there is PA apoplexy, the ischemia and hypoxia of the cystic group are lesser than those of the parenchymal group, but the proliferation is stronger.

Background: Studies have shown that circular RNAs (circRNAs) have significant potential as novel molecular markers for the diagnosis, treatment, and prognosis of prostate carcinoma (PCa). However, the role and mechanism of circRNA hsa_circ_0102485 in PCa remains unclear. Materials & methods: The real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to quantify hsa_circ_0102485 expression in PCa. The potential mechanisms and roles of hsa_circ_0102485 in tumor growth were explored using dual-luciferase-reporter and subcutaneous-xenograft assays, rescue experi-ments, and immunohistochemical staining. Clinical correlations were assessed by tissue-on-a-chip in-situ hy-bridization and Fisher's exact test. Results: Hsa_circ_0102485 expression was decreased in PCa, and overexpression of hsa_circ_0102485 suppressed the proliferation, metastasis, invasion, and antiapoptotic abilities of PCa cells. MicroRNA 188-3p (MiR-188-3p) is a direct target of hsa_circ_0102485, and cotransfection of hsa_circ_0102485 in PCa cells overexpressing miR-188-3p inhibited its promotive effects. Hsa_circ_0102485 indirectly promotes the expression of AT-rich inter-action domain 5B (ARID5B) and androgen receptor (AR) by sponging miR-188-3p and inhibiting PCa cell growth. Correlation analysis showed that hsa_circ_0102485 expression in PCa was not significantly correlated with the age, International Society of Urologic Pathologists (ISUP) grade, Gleason score, or lymph node metastasis status of PCa patients. Conclusion: Hsa_circ_0102485 plays an inhibitory role in PCa by regulating the Mir-188-3p/ARID5B/AR axis and may be a potential diagnostic biomarker and therapeutic target for PCa that requires further study.

[This corrects the article DOI: 10.3892/ol.2016.5514.].

Long noncoding RNAs (lncRNAs) and their crosstalks with other RNAs have been revealed to be closely related to tumorigenesis and development, but their role in invasive pituitary adenoma (IPA) remains largely unclear. In our study, LINC00473 was identified as the most upregulated lncRNA in IPA by whole transcriptome RNA sequencing (RNA-Seq). Further, its related signaling pathway LINC00473/miR-502-3p/KMT5A was obtained by constructing a competing endogenous RNA (ceRNA) regulatory network. Their expression in IPA and non-invasive pituitary adenoma (NIPA) tissues was verified by qRT-PCR. Then the effects and mechanisms of LINC00473 and its ceRNA network on the proliferation of pituitary adenoma (PA) cells were confirmed by gene overexpression or silencing techniques combined with CCK-8 assay, EdU staining, flow cytometry assay, and double luciferase reporter gene assay in PA cell lines AtT-20 and GT1-1 in vitro and in a xenograft model in vivo. LINC00473 is overexpressed in IPA and can promote PA cells proliferation. Mechanistically, overexpression of LINC00473 restricts miR-502-3p through the ceRNA mechanism, upregulates KMT5A expression, and promotes the expression of cyclin D1 and CDK2, which is conducive to the cell cycle process, thereby promoting the proliferation of PA cells, involving IPA progression.

Background: Thoracic solitary fibrous tumors (TSFT) are a rare disease. We aim to determine the prognostic factors related to survival of TSFT patients through the use of The Surveillance, Epidemiology, and End Results database to analyze demographic and clinical characteristics. This study is intended to determine the prognostic factors associated with TSFT and has clinical value. Patients and Methods: This is a retrospective study of patients who were diagnosed with TSFT in the SEER database from 2001 to 2015. The kaplan-Meier method and Cox regression analysis were used to identify prognostic factors for patient survival. Results: From the SEER database (2001-2015), 227 patients with TSFT were detected. The 5-year survival rate was 82.7%, and the 10-year survival rate was 62.4%. Surgical resection [HR 0.314, 95% CI 0.201-0.491, P <0.001] was just an independent factor in the improvement of patient prognosis. Conclusion: The results of this study indicate that the prognostic factors for TSFT patients are age, grade, surgery, and chemotherapy. Age <65 years old, well-differentiated, surgery instead of chemotherapy is a favorable prognostic factor for survival of TSFT patients.

Objective Although the significance of increased plasma D-dimer levels in activating coagulation and fibrinolysis has been reported, it is still controversial whether it can be used to predict the prognosis of lung cancer patients. This meta-analysis was performed to explore the beneficial role of plasma D-dimer as a prognostic factor in lung cancer patients according to a larger sample capacity. Materials and methods MEDLINE, EMBASE, and Cochrane Central databases were searched from inception to January 2021. The data are mainly hazard ratio(HR) with 95% confidence interval (CI) and Kaplan–Meier survival curves. The publication bias was examined by Egger’s test. Results Finally, a total of 28 studies, enrolling 8452 patients were included in the current meta-analysis. Our results showed that the OS (HR = 1.742, 95%CI:1.542–1.969, P < 0.001) and PFS (HR = 1.385, 95%CI:1.169–1.641, P = 0.003) in the high D-dimer group were significantly lower than those in the low D-dimer group. Subgroup analysis suggested that localization, detection methods and disease stage had an important effect on the prognosis. Conclusion This meta-analysis revealed that the high plasma D-dimer level leads to lower survival than in the low D-dimer level, which might provide an important clue for high plasma D-dimer level as an independent factor of poor prognosis in patients with lung cancer.

Prostate cancer remains a significant cause of cancer-related deaths in male population. More recently, accumulating evidence continues to implicate long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in various types of cancers, including prostate cancer. The current study aimed to elucidate the role of lncRNA AGAP2-AS1/miR-195-5p/PDZ and LIM domain 5 (PDLIM5) in prostate cancer progression. Initially, microarray expression profiles were applied to screen differentially expressed lncRNAs/miRNAs/genes associated with prostate cancer. Dual-luciferase reporter and RNA pull-down/RIP assays were subsequently performed to explore the interactions among lncRNA AGAP2-AS1, miR-195-5p, and PDLIM5, after which their expression was detected in cancer tissues and cells. Next, gain- and loss-of-function approaches were employed to elucidate the mechanism of lncRNA AGAP2-AS1/miR-195-5p/PDLIM5 in the processes of cell proliferation, migration and invasion as well as tumor growth. LncRNA AGAP2-AS1 was found to be highly expressed in prostate cancer. Silencing of lncRNA AGAP2-AS1 contributed to the suppression of proliferation, migration and invasion of cancer cells in vitro. Besides, lncRNA AGAP2-AS1 could bind to miR-195-5p which targeted PDLIM5 and subsequently downregulated its expression, ultimately impeding the progression of prostate cancer. Additionally, lncRNA AGAP2-AS1 inhibition led to an up-regulated expression of miR-195-5p and down-regulated PDLIM5 expression, resulting in delayed tumor growth in vivo. Taken together, the key findings of our study demonstrated that lncRNA AGAP2-AS1 silencing exerted suppressive effects on the development of prostate cancer via the miR-195-5p-dependent downregulation of PDLIM5. Our findings highlighted the potential of lncRNA AGAP2-AS1 as a promising novel molecular target for prostate cancer therapy.

Hypoxia is a common phenomenon in pituitary adenomas (PAs). The role and mechanism of hypoxia in the PAs remains elusive. This work aimed to explore the effect of hypoxia on PAs in vitro. PA cells GT1-1 were cultured and treated under hypoxic condition. Cell proliferation assay showed the proliferation of PA cells was increased significantly by hypoxia treatment, with a peak at 12 hours. qPCR and western blot indicated that the expression of HIF-1α, ALKBH5, and Nanog were elevated by hypoxia stimuli. In conclusion, our funding demonstrated that hypoxia could increase Nanog expression through HIF-1α/ALKBH5 signaling, thereby promoting the proliferation of PA cells.

Background Although the incidence and clinical manifestations of pituitary apoplexy were reported by a few researches, the results are not consistent. This study aimed to explore the risk factors associated with an incidence of apoplexy in pituitary adenomas. Methods The clinical information of 843 patients with pituitary adenoma from the Department of Neurological Surgery, 1st Affiliated Hospital of Kunming Medical University, was reviewed. The incidence, clinical manifestation, and potential risk factors for pituitary apoplexy were analyzed by a case-control study. Results In total, 121 patients (14.4%) with macroadenoma were suffered from pituitary apoplexy. Headache, vomiting, and visual impairment are the top 3 symptoms for the pituitary apoplexy. Logistic regression results showed that the hypertension(hypertension vs non-hypertension OR = 2.765, 95%CI:1.41~5.416), tumor type (negative staining vs. positive staining, OR = 1.501, 95%CI:1.248~5.235), and tumor size (diameter > 2 cm vs. diameter ≤ 2 cm, OR = 3.952, 95%CI:2.211~7.053) are independent factors associated with pituitary apoplexy. Conclusion Our results indicate that the risk factors for the incidence of pituitary apoplexy depend mainly on properties of the tumor itself (tumor size and pathologic type) and the blood pressure of patients.

Abstract Background An increasing number of studies have reported circular RNAs (circRNAs) as new potential biomarkers for the prognosis of gliomas. However, the overall prognostic value of circRNAs for glioma remains unclear. Therefore, this study is the first comprehensive evaluation of the clinicopathological and prognostic value of dysregulated circRNAs in the treatment of glioma patients. Methods We systematically reviewed the online databases of PubMed, Web of Science, EMBASE, and Cochrane Library to identify studies that explored the relationship between circRNA expression and clinicopathological and prognostic factors in glioma through April 11, 2020. The quality of the included studies was evaluated by the Newcastle-Ottawa Scale (NOS) checklists. Clinicopathological features were assessed by pooled odds ratios (ORs) and 95% confidence intervals (CIs), and overall survival (OS) was assessed by hazard ratios (HRs) and 95% CIs. Results Twenty-four eligible studies, including 22 studies of clinicopathological features, 1 diagnostic study, and 18 studies of prognosis, that included a total of 1390 patients were ultimately included in this study. Meta-analysis showed that highly expressed oncogenic circRNAs were significantly related to poor clinicopathological features (age: P = 0.026; tumor size: P ≤ 0.001; tumor grade: P ≤ 0.001; KPS: P = 0.012) and worse overall survival (OS) (HR = 2.01, 95% CI: 1.61–2.50, P ≤ 0.001). Moreover, we found that highly expressed tumor-suppressor circRNAs were related to better clinicopathological features (gender: P = 0.042; age: P = 0.014; tumor size: P = 0.022; tumor grade: P ≤ 0.001) and longer OS (HR = 2.70, 95% CI: 1.82–3.99, P ≤ 0.001). Conclusions In conclusion, there is a significant correlation between the dysregulated expression of circRNAs and the clinicopathology and prognosis of glioma patients.

Objective To explore the mechanism of hypoxia inducing interleukine (IL)-11 secretion in anaplastic thyroid carcinoma (ATC) cells and the mechanism of IL-11 promoting epithelial mesenchymal transition of ATC cells.Methods Knockdown of IL-11,hypoxia-inducible factor (HIF)-1α in ATC cells or treatment of ATC cells with Cobalt Chloride,recombinant human interleukin (rhIL)-11,IL-11 antibody,then the effects of these interventions on the invasion and migration ability of ATC cells and its mechanism were detected by enzyme-linked immunosorbent assay (ELISA),Transwell,Real-time polymerase chain reaction (PCR),Western blotting.Results Under treatment with Cobalt Chloride,the protein and mRNA expression of IL-11 increased in ATC cells.The number of invasive cells in the knockdown HIF-1α group (61.7 ±4.9,30.0 ±4.6) was less than that of the control group 261.7 ± 8.7 (P ＜ 0.01),and the number of migrated cells (87.3 ± 4.5,73.8 ± 5.4) was less than the control group 337.3 ± 7.1 (P ＜ 0.01).The expression ofphosphorylated Akt (p-Akt),phosphorylated glycogen synthase kinase 3β (p-GSK3β) and Snail protein was significantly increased after treatment with rhIL-11.The protein expression of p-Akt,p-GSK3β and Snail were significantly decreased after knockdown of IL-11 expression in ATC cells.Conclusion Hypoxia induced epithelial mesenchymal transition of ATC cells is the main mechanism of high invasion and migration of ATC cells.

Background:Dysregulation of microRNAs (miRNAs) plays a critical role during the occurrence and progress of pituitary adenomas (PAs).However,the roles of miRNAs in the invasiveness of PA are poorly understood.This study aims to more comprehensively and specific define the relationship between altered miRNA and PA invasion.Methods:The differential expression of miRNAs (DEMs) between invasive PAs (IPAs) and non-invasive PAs (NPAs)was explored by RNA sequencing and which functions were analyzed by gene ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG).The miRNA-mRNA network was predicted with bioinformatics.Results:We identified 31 upregulated miRNAs and 24 downregulated miRNAs in IPAs compared with NPAs.GO analysis and KEGG pathway analysis showed the DEMs were mainly associated with cell proliferation and cell cycle pathway.In addition,on the count of predicted miRNA-mRNA network,two hub miRNAs were identified.Conclusions:Our results demonstrate the miRNA-mRNA network in detail,which suggest that miRNA may be a promising target in diagnosis and therapy for IPAs.

Neural stem cells (NSCs) transplantation is considered a promising treatment for Parkinson's disease. But most NSCs are differentiated into glial cells rather than neurons, and only a few of them survive after transplantation due to the inflammatory environment.

Platelet counts have been reported to be closely related to distant metastasis of many malignant tumors. Our previous study showed that elevated peripheral blood platelet counts may be an adverse prognostic factor of anaplastic thyroid carcinoma (ATC) patients, indicating that platelets may promote ATC progression. In the present study, we aimed to identify the role of platelets in ATC cell invasion and migration and to explore the underlying mechanisms. We found that platelets can promote the invasive and migratory of ATC cells, which may be related to the interaction between activated platelet-secreted chemokine (C-C motif) ligand 3 (CCL3) and its receptor CCR5. The interaction was shown to induce the upregulation of matrix metalloproteinase (MMP)-1 via NF-κB pathway. These findings could provide a new idea for the research of targeted platelets to inhibit tumor metastasis.

Background: Radiotherapy and chemotherapy are the two important postoperative management approaches for anaplastic thyroid carcinoma (ATC), and several studies have suggested that postoperative radiotherapy and chemotherapy can prolong the survival of patients with ATC. However, the results remain inconsistent. Objective: A meta-analysis was performed to address whether postoperative radiotherapy and chemotherapy could prolong the survival of patients with ATC. Methods: Relevant studies were included, and pooled hazard ratios (HRs) together with 95% confidence intervals (CIs) were calculated. Results: Ten relevant studies on factors that affect the prognosis for ATC were included in this meta-analysis, evaluating a total of 1,163 patients. The pooled HR for overall survival (OS) was calculated using a random-effects model. The pooled results demonstrated that for all patients with resectable ATC, the combination of surgery and radiotherapy significantly reduced the risk of death compared with surgery alone (HR =0.51, 95% CI: 0.36-0.73, Z=3.66, P=0.0002). To investigate the prognostic impacts of chemotherapy in patients with ATC, we also calculated the pooled HR of chemotherapy for OS using a random-effects model; however, the pooled results suggested that chemotherapy did not prolong the survival of ATC patients compared with controls (HR =0.63, 95% CI: 0.33-1.21, Z=1.39, P=0.17). Conclusion: This study provided evidence that currently, for patients with ATC, postoperative radiotherapy may prolong survival; in contrast, chemotherapy did not improve long-term survival.

The role of autophagy in tongue squamous cell carcinoma (TSCC) cisplatin resistance is unclear. We aimed to identify a possible synergistic effect of autophagy inhibitors and cisplatin in TSCC cells and explore the underlying mechanism. Our results indicate that autophagic flux was high in TSCC cells; Autophagy inhibitor bafilomycin A1 increased cisplatin cytotoxicity in TSCC cells by inhibiting lysosomal uptake of platinum and enhancing intracellular platinum ion binding to DNA; Autophagy gene (Atg5) knockout in TSCC cells did not duplicate the above-mentioned sensitization of bafilomycin A1. Furthermore, we found that cisplatin resistance of TSCC cells was related to cisplatin inducing lysosome biogenesis in a TFEB-dependent manner, which was regulated by c-Abl. In summary, this is the first study to show that Bafilomycin A1 increases the sensitivity of TSCC cells to cisplatin by inhibiting lysosomal function but not autophagy. Lysosomes may be a potential target to increase cisplatin cytotoxicity toward TSCC cells.

MicroRNAs (miRNA) are a class of small, noncoding RNA molecules that regulate the expression of target genes. miRNA dysregulation is involved in carcinogenesis and tumor progression. In this study, we identified microRNA-1253 (miR-1253) as being significantly down-regulated in non-small-cell lung carcinoma (NSCLC) tissues and associated with advanced clinical stage, lymph node metastasis, and poor survival. The enhanced expression of miR-1253 significantly inhibited the proliferation, migration, and invasion of NSCLC cells in vitro. Bioinformatics analyses showed that miR-1253 directly targeted WNT5A (long isoform), which was confirmed using the dual-luciferase reporter assay. The inhibitory effects of miR-1253 on the growth and metastasis of NSCLC cells were attenuated and phenocopied by WNT5A (long) overexpression and knockdown, respectively. Consistent with the in vitro results, subcutaneous tumor and metastatic NSCLC mouse models showed that miR-1253 functions as a potent suppressor of NSCLC in vivo. Taken together, our findings indicated that miR-1253 inhibited the proliferation and metastasis of NSCLC cells by targeting WNT5A (long isoform) and provided new evidence of miR-1253 as a potential therapeutic target in NSCLC.

OBJECTIVES:To investigate the effect of glycopeptide-preferring polypeptide GalNAc transferase 1 (ppGalNAc T1) targeted RNA interference (RNAi) on the growth and migration of human bladder carcinoma EJ cells in vitro and in vivo.METHODS:DNA microarray assays were performed to determine ppGalNAc Ts(ppGalNAc T1-9) expression in human bladder cancer and normal bladder tissues. We transfected the EJ bladder cancer cell line with well-designed ppGalNAc T1 siRNA. Boyden chamber and Wound healing assays were used to investigate changes of shppGalNAc T1-EJ cell migration. Proliferation of shppGalNAc T1-EJ cells in vitro was assessed using [3H]-thymidine incorporation assay and soft agar colony formation assays. Subcutaneous bladder tumors in BALB/c nude mice were induced by inoculation of shppGalNAc T1-EJ cells and after inoculation diameters of tumors were measured every 5 days to determine gross tumor volumes.RESULTS:ppGalNAc T1 mRNA in bladder cancer tissues was 11.2-fold higher than in normal bladder tissues. When ppGalNAc T1 expression in EJ cells was knocked down through transfection by pSUPER-shppGalNAc T1 vector, markedly reduced incorporation of [3H]-thymidine into DNA of EJ cells was observed at all time points compared with the empty vector transfected control cells. However, ppGalNAc T1 knockdown did not significantly inhibited cell migration (only 12.3%). Silenced ppGalNAc T1 expression significantly inhibited subcutaneous tumor growth compared with the control groups injected with empty vector transfected control cells. At the end of observation course (40 days), the inhibitory rate of cancerous growth for ppGalNAc T1 knockdown was 52.5%.CONCLUSION:ppGalNAc T1 might be a potential novel marker for human bladder cancer. Although ppGalNAc T1 knockdown caused no remarkable change in cell migration, silenced expression significantly inhibited proliferation and tumor growth of the bladder cancer EJ cell line.