High expression of eIF4A1 predicts unfavorable prognosis in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a worldwide malignancy with high morbidity and mortality. Translation initiation factor 4A1 (eIF4A1), which is an ATP-dependent RNA helicase as a part of eIF4F complex, has been linked to malignant transformation and progression, and a variety of cancers display dysregulation of this enzyme. However, its role in ccRCC remains unclear. In our study, we examined its potential effects in ccRCC. METHODS: Based on Proteomic data, TCGA and ONCOMINE database, RCC cell lines and tissues, the expression of eIF4A1 between ccRCC and normal tissues were investigated. A correlation was evaluated between the prognostic model for OS and ccRCC progression. Analysis of functional enrichment and PPI network were performed. After examining differentially expressed genes between the eIF4A1 high and low-expression groups, we performed GSEA analysis. Furthermore, we investigated immune cell infiltration of eIF4A1. Then we determined eIF4A1 functions in the establishment and maintenance of cell viability, migration and invasion of cell lines. Flow cytometry was utilized to detect cell cycle. RESULTS: The eIF4A1 was up-regulated in ccRCC tissues and cell lines. An increased level of eIF4A1 was linked to lower survival rates and impaired immunity. Depletion of eIF4A1 could arrest tumor cells in G1 phase, so as to seriously limit cell proliferation and weaken the capacity of cell migration. CONCLUSION: ccRCC patients with high eIF4A1 expression are at increased risk of poor prognosis, furthermore eIF4A1 plays a prominent role in facilitating tumor cell proliferation and migration which may further be a potential prognostic biomarker and therapeutic target.

Melamine-induced urinary calculi in infants--sonographic manifestations and outcomes 1 year after exposure.

BACKGROUND: In 2008, the melamine-tainted-milk incident started with reports of increased incidence of urolithiasis in infants in China. Affected children were screened for urolithiasis. OBJECTIVE: The purpose of this study was to analyze sonographic characterization of infant melamine-induced urolithiasis. MATERIALS AND METHODS: Transabdominal US examination was done in 603 infants with melamine-induced calculi. The imaging characteristics of calculi and hydronephrosis were analyzed. Follow-up US imaging was performed. RESULTS: Comet-tail sign was seen behind the calculus of <4 mm. Calculi of ≥ 4 mm were found in 299 inpatients with clear posterior border and with or without light shadowing. Solitary and multiple stones had similar incidence. Incidence of calculi in the inferior renal calyx was the highest (55.2%) in inpatients. Calculus size in inpatients age 2-3 years was smaller than that of children younger than 2 years old (P < 0.05). Inpatients age 2-3 years had the highest incidence rate (48.0%) of hydronephrosis. CONCLUSION: Calculi of <4 mm manifested as hyperechoic foci near the renal papillae, while calculi of ≥ 4 mm usually manifested as echogenic foci with visible inferior edge in the renal calyx. Hydronephrosis was a common imaging finding in inpatients ages 2-3 years.

Intravesical Bacillus Calmette-Guérin versus epirubicin for Ta and T1 bladder cancer.

BACKGROUND: Bladder cancer accounts for approximately 4.4% of adult malignancies, and approximately 80% of bladder cancer presents initially as transitional cell carcinoma that is confined to the urothelium (stage Ta) or lamina propria (stage T1). Intravesical administration of Bacillus Calmette-Guérin (BCG) and epirubicin (EPI) has been proven to reduce tumour recurrence and prevent or delay progression to muscle invasion and metastases. However, comparison of the effectiveness and safety of intravesical BCG and EPI in bladder cancer has yet to be explored. OBJECTIVES: To compare the effectiveness and safety of BCG with EPI in the treatment of Ta and T1 bladder cancer. SEARCH STRATEGY: A comprehensive search of MEDLINE (1966 to April 2010), EMBASE (1980 to April 2010), Health Services Technology, Administration, and Research (HealthSTAR), the Cochrane Central Register of Controlled Trials (CENTRAL), CancerLit, and Database of Abstracts of Reviews of Effectiveness (DARE), was performed, and handsearching of relevant journals was undertaken. SELECTION CRITERIA: All randomised or quasi-randomised trials (in which allocation was obtained by alternation - e.g., alternate medical records, date of birth, or other predictable methods) in patients with Ta or T1 bladder cancer that compared intravesical BCG with EPI were included. No language restrictions were applied. DATA COLLECTION AND ANALYSIS: Trial eligibility, methodological quality and data extraction were assessed independently by two reviewers. We compared dichotomous outcomes (frequency of tumour recurrence, progressive disease by stage, mortality, distant metastases, local and systemic adverse effects, treatment delayed or stopped due to adverse effects) using risk ratios (RR) with 95% confidence intervals (CI). MAIN RESULTS: Five trials of 1111 participants were included in this review. For BCG, 549 patients were treated, and 562 with EPI. Of the evaluated patients, 35.5% (195/549) in the BCG group and 51.4% (289/562) in the EPI group had tumour recurrence (P < 0.05). For disease progression (BCG, 44/549; EPI, 58/562) and distant metastases (BCG, 23/487; EPI, 31/495), there were no significant differences (P = 0.19 and P = 0.29, respectively). Only two trials, including 769 patients, had sufficient data for us to analyze disease-specific (BCG, 22/383; EPI, 26/386) and overall mortality (BCG, 125/383; EPI, 147/386). Neither comparison was significant (P = 0.93 and P = 0.12, respectively). In four studies reporting toxicity, BCG was associated with significantly more drug-induced cystitis [BCG, 54.1% (232/429); EPI, 31.7% (140/441)] and haematuria [BCG, 30.8% (132/429); EPI, 16.1% (71/440)]. Similarly, in three studies reporting systemic toxicity, BCG had significantly higher toxicity than the EPI (34.8% (134/385) versus 1.3% (5/393), respectively). In a meta-analysis comparing 'treatment delayed or stopped' (BCG, 40/431; EPI, 33/441), there was no significant difference between BCG and EPI treatments (P = 0.82). AUTHORS' CONCLUSIONS: The data from the present meta-analysis indicate that intravesical BCG treatment is more efficacious than EPI in reducing tumour recurrence for Ta and T1 bladder cancer. However, BCG appears to be associated with a higher incidence of adverse effects, such as drug-induced cystitis, haematuria and systemic toxicity, than EPI. The overall quality of the evidence is rather low. Well-designed, high quality randomised controlled trials with good allocation concealment are required.

Dendritic cell transfected with secondary lymphoid-tissue chemokine and/or interleukin-2 gene-enhanced cytotoxicity of T-lymphocyte in human bladder tumor cell S in vitro.

OBJECTIVES: The aim of this study was to investigate whether dendritic cells (DCs) transfected with human secondary lymphoid-tissue chemokine (hSLC) and human interleukin-2 (hIL-2) genes are capable of improving DC's proliferation and to produce a marked antitumor effect in vitro combined with T-lymphocyte (TC). METHODS: SLC gene primer was designed based on the corresponding gene sequence in GenBank. The Kpn I site was introduced into the upstream of the primer and Xho I site into the downstream. The SLC gene was amplified with the template of pET32a(+)-SLC by polymerase chain reaction. SLC was cloned into pBudCE4.1/IL-2 (TRAIL was cut from pBudCE4.1/TRAIL- IL-2 before) to construct recombinant plasmid pBudCE4.1/SLC-IL-2(PSI). DCs were transfected with pBudCE4.1/SLC-IL-2 by gene electric transfection. Protein expression was determined with Western blot and enzyme-linked immunosorbent assays. Cytotoxicity of TC and DC against the human bladder tumor cell were examined by chromium release assay. Flow cytometric analyses were performed to determine the apoptosis of tumor cells and the percentage of Treg. RESULTS: A high level of expression of SLC and IL-2 was observed in DCs transfected with SLC and IL-2 genes. The mean production of IL-2 was 19.8 +/- 2.5, 511.10 +/- 52.36, and 541.3 +/- 62.04 ng/10(6) cells/24 hours in the DC/vector, DC/IL-2, and DC/SLC-IL-2, respectively. The mean SLC production was 29.8 +/- 4.43, 506.10 +/- 42.36, and 567.34 +/- 52.05 ngs/10(6)cells/24 hours in the DC/ vector, DC/SLC, and DC/SLC-IL-2, respectively. Cytotoxicity to bladder cancer cells was increased. The mean cytotoxicity (the effector/target ratio, 40:1) of TC-DC/parental, TC-DC/IL-2, TC-DC/SLC, and TC-DC/SLC-IL-2(TDSI) to the human bladder cancer cells was 32.1 +/- 5.5%, 63.5 +/- 6.6%, 78.1 +/- 9.63%, respectively. The apoptotsis rate of bladder cancer cells treated with TDSI was 18.6% by flow cytometry. Treg cells' percentage was very small in the DC medium. CONCLUSIONS: SLC and IL-2 were produced by autocrine in DCs transfected with SLC and IL-2 genes. DC/SLC-IL-2 can promote DC proliferation, while TC-DC/SLC-IL-2 and TC-DC/SLC could strongly enhance significant cytotoxicity against bladder cancer cell that was induced by the coculture of DCs (transfected with SLC and IL-2) and TC.