LncRNA GAS5 participates in childhood pneumonia by inhibiting cell apoptosis and promoting SHIP-1 expression via downregulating miR-155.

BACKGROUND: LncRNA GAS5 and miR-155 are reported to play opposite roles in lung inflammatory responses. Lung inflammation participates in childhood pneumonia, indicating the involvement of GAS5 and miR-155 in pneumonia. The study aimed to analyze the potential interaction between GAS5 and miR-155 in childhood pneumonia. METHODS: GAS5 and miR-155 levels in plasma samples from pneumonia patients and controls were detected using RT-qPCR. The role of GAS5 in miR-155 RNA gene methylation in human bronchial epithelial cells (HBEpCs) was analyzed by methylation analysis. Flow cytometry and RT-qPCR were applied to analyze cell apoptosis and SHIP-1 expression, respectively. RESULTS: GAS5 was downregulated in pneumonia, and miR-155 was upregulated in pneumonia. GAS5 and miR-155 were inversely correlated. GAS5 overexpression decreased miR-155 expression in HBEpCs, while miR-155 overexpression showed no significant effects on GAS5 expression. In addition, GAS5 suppressed LPS-induced HBEpC apoptosis, promoted SHIP-1 expression, and reduced the enhancing effect of miR-155 on cell apoptosis and SHIP-1 expression. CONCLUSIONS: GAS5 may participate in childhood pneumonia by inhibiting cell apoptosis and promoting SHIP-1 expression via downregulating miR-155.

lncRNA BCAR4 Increases Viability, Invasion, and Migration of Non-Small Cell Lung Cancer Cells by Targeting Glioma-Associated Oncogene 2 (GLI2).

This study aimed to explore the effects of lncRNA BCAR4 on the viability and aggressiveness of non-small cell lung cancer (NSCLC) cells. qRT-PCR was used to determine the expression of BCAR4 and GLI2 downstream genes in NSCLC tissues and cell lines. Chromatin isolation by RNA purification (CHIRP) and Western blot were employed to measure the expression of the GLI2 downstream proteins. Ki-67 expression in nude mice tumors was tested by immunohistochemistry. MTT assay, wound healing assay, and Transwell assay were used to assess NSCLC cell viability and aggressiveness, respectively. Tumor xenograft was conducted to determine the effects of BCAR4 and GLI2 on NSCLC tumorigenesis in vivo. The expression of BCAR4 in NSCLC tissues and cells was significantly higher than the normal level. The overexpression of BCAR4 promoted NSCLC cell viability, migration, and invasion. The suppression of BCAR4 and GLI2 showed the opposite effects. The overexpression of BCAR4 led to an increase in the expression of GLI2 downstream proteins, while the suppression of BCAR4 and GLI2 reduced their expression. In a tumor xenograft assay, the tumors in mice of the BCAR4 group showed the biggest volume, while those in mice of the si-GLI2 group showed the smallest volume. Ki-67 showed much higher levels in the BCAR4 overexpression group but much lower levels in the si-GLI2 group. In summary, the cooperative mechanism of lncRNA BCAR4 and GLI2 might provide a new opportunity for treating NSCLC.

NMP-22, urinary cytology, and cystoscopy: a 1 year comparison study.

INTRODUCTION: Bladder cancer diagnosis and surveillance is costly and frequent. Urinary cytology is used with cystoscopy in the diagnosis and surveillance of bladder cancer with little evidence to support this practice. Nuclear Matrix Protein-22 (NMP-22) is a marker of urothelial cell death and is elevated in the urine of patients with bladder cancer. Our study compares the performance of NMP-22, urinary cytology and office cystoscopy when utilized in a Veteran Affairs urology practice for 1 year. MATERIALS AND METHODS: A total of 391 consecutive office cystoscopy procedures performed over 1 year were included in the study. NMP-22 and cytology were performed on the urine specimens of patients presenting for cystoscopy. Tumor resection/bladder biopsy was performed when cystoscopy, NMP-22 or urinary cytology were abnormal. RESULTS: Cystoscopy, NMP-22, and urinary cytology data were available in 351 encounters and 69 tumor resections were performed. Urothelial carcinoma bladder (UCB) was identified in 37 bladder specimens. NMP-22, urinary cytology and cystoscopy demonstrated sensitivity and specificity of (51%/96%), (35%/97%), and (92%/88%), respectively. NMP-22 cost $8,750 in the study group and urinary cytology cost $52,500 in the same group. CONCLUSIONS: This study demonstrates cystoscopy was the most sensitive test in the diagnosis of UCB. NMP-22 had a higher sensitivity than urinary cytology and similar specificity to cytology. Additional urinary marker testing has a limited role in the management of bladder cancer in the office setting. When adjunct testing is desired in the diagnosis and surveillance of bladder cancer, NMP-22 is a cost effective alternative to urinary cytology.

Systematic review of the clinical effectiveness and cost-effectiveness of photodynamic diagnosis and urine biomarkers (FISH, ImmunoCyt, NMP22) and cytology for the detection and follow-up of bladder cancer.

OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of photodynamic diagnosis (PDD) compared with white light cystoscopy (WLC), and urine biomarkers [fluorescence in situ hybridisation (FISH), ImmunoCyt, NMP22] and cytology for the detection and follow-up of bladder cancer. DATA SOURCES: Major electronic databases including MEDLINE, MEDLINE In-Process, EMBASE, BIOSIS, Science Citation Index, Health Management Information Consortium and the Cochrane Controlled Trials Register were searched until April 2008. REVIEW METHODS: A systematic review of the literature was carried out according to standard methods. An economic model was constructed to assess the cost-effectiveness of alternative diagnostic and follow-up strategies for the diagnosis and management of patients with bladder cancer. RESULTS: In total, 27 studies reported PDD test performance. In pooled estimates [95% confidence interval (CI)] for patient-level analysis, PDD had higher sensitivity than WLC [92% (80% to 100%) versus 71% (49% to 93%)] but lower specificity [57% (36% to 79%) versus 72% (47% to 96%)]. Similar results were found for biopsy-level analysis. The median sensitivities (range) of PDD and WLC for detecting lower risk, less aggressive tumours were similar for patient-level detection [92% (20% to 95%) versus 95% (8% to 100%)], but sensitivity was higher for PDD than for WLC for biopsy-level detection [96% (88% to 100%) versus 88% (74% to 100%)]. For more aggressive, higher-risk tumours the median sensitivity of PDD for both patient-level [89% (6% to 100%)] and biopsy-level [99% (54% to 100%)] detection was higher than those of WLC [56% (0% to 100%) and 67% (0% to 100%) respectively]. Four RCTs comparing PDD with WLC reported effectiveness outcomes. PDD use at transurethral resection of bladder tumour resulted in fewer residual tumours at check cystoscopy [relative risk, RR, 0.37 (95% CI 0.20 to 0.69)] and longer recurrence-free survival [RR 1.37 (95% CI 1.18 to 1.59)] compared with WLC. In 71 studies reporting the performance of biomarkers and cytology in detecting bladder cancer, sensitivity (95% CI) was highest for ImmunoCyt [84% (77% to 91%)] and lowest for cytology [44% (38% to 51%)], whereas specificity was highest for cytology [96% (94% to 98%)] and lowest for ImmunoCyt [75% (68% to 83%)]. In the cost-effectiveness analysis the most effective strategy in terms of true positive cases (44) and life-years (11.66) [flexible cystoscopy (CSC) and ImmunoCyt followed by PDD in initial diagnosis and CSC followed by WLC in follow-up] had an incremental cost per life-year of over 270,000 pounds. The least effective strategy [cytology followed by WLC in initial diagnosis (average cost over 20 years 1403 pounds, average life expectancy 11.59)] was most likely to be considered cost-effective when society's willingness to pay was less than 20,000 pounds per life-year. No strategy was cost-effective more than 50% of the time, but four of the eight strategies in the probabilistic sensitivity analysis (three involving a biomarker or PDD) were each associated with a 20% chance of being considered cost-effective. In sensitivity analyses the results were most sensitive to the pretest probability of disease (5% in the base case). CONCLUSIONS: The advantages of PDD's higher sensitivity in detecting bladder cancer have to be weighed against the disadvantages of a higher false-positive rate. Taking into account the assumptions made in the model, strategies involving biomarkers and/or PDD provide additional benefits at a cost that society might be willing to pay. Strategies replacing WLC with PDD provide more life-years but it is unclear whether they are worth the extra cost.

Economic evaluation of NMP22 in the management of bladder cancer.

The purpose of this study was to evaluate, from the perspective of the Quebec health system, the cost and cost-efficacy of using NMP22 compared with the currently recommended monitoring procedure following a transurethral resection of a bladder tumor (TURBT). This evaluation was based on results from the study by Soloway, et al. It was performed using a decision analysis technique which compared a follow-up modality using NMP22 with the conventional follow-up monitoring procedure for the first 6 months after an initial transurethral resection of a bladder tumor. Each routine cystoscopy and cytology costs a total of $155. For the 6 months following initial TURBT, the cost for standard follow-up monitoring totaled $311, while the cost for the NMP22 monitoring modality was $257. On average, using NMP22 would have saved $55 per patient during the first 6 months of follow-up, resulting in a cost saving of approximately 18%. As well, 64.3% of patients would have undergone only one cystoscopy during the 6 month period, instead of the two done using the conventional modality. The trade-off for using NMP22 is that some patients would have a 3 month delay before diagnosis of a recurrence. This would occur in 8.9% of patients. NMP22 is less expensive than conventional monitoring follow-up of bladder cancer, and it can decrease patient discomfort by reducing the need for cystoscopy. Implementing it as routine follow-up monitoring should be considered, particularly for patients with low-grade tumors.

NMP22 is a sensitive, cost-effective test in patients at risk for bladder cancer.

PURPOSE: The early diagnosis of bladder cancer is central to its effective treatment. This study was designed to determine the clinical use of NMP22 as a urinary marker for the early detection of transitional cell carcinoma of the bladder in patients with hematuria or other indications at risk for malignancy. The sensitivity and specificity of the NMP22 test were compared with urinary cytology, and the results of both tests were then compared to cystoscopic findings. We also determined if NMP22 provided a cost advantage over our current modalities in our patient population. MATERIALS AND METHODS: Each patient submitted a single voided urine which was divided in 2 parts, of which 1 was stabilized with the NMP22 urine collection kit and 1 was preserved in the appropriate cytology medium for cytopathological testing. All patients provided the urine samples before cystoscopic examination. Of the 330 patients 114 (34.5%) presented with microscopic hematuria and 66 (20.4%) with gross hematuria. Other indications for cystoscopy included atypical cytology or unexplained voiding symptoms refractory to medical therapy. RESULTS: There were 18 patients with biopsy confirmed bladder cancer and 312 with benign conditions of the bladder. Median NMP22 value for the malignant bladder tumors was 31.6 units per ml. (95% confidence interval 13.4 to 90.9) and 4.3 units per ml. (3.8 to 4.8) for benign conditions of the bladder. The urinary NMP22 values in the bladder cancer group were significantly higher than those in the benign condition group (p <0.001). The sensitivity of NMP22 was 100% with a specificity of 85% at a reference value of 10.0 units per ml., while cytology had a sensitivity of only 33% and specificity of 100%. Given a negative predictive value of 100% for NMP22, a cost savings of $28,302 to $111,072 (depending on the type of insurance carrier) would have been achieved if it was used alone as the indication for cystoscopy. CONCLUSIONS: This study indicates that urinary NMP22 is a simple, noninvasive, cost-effective marker for the detection of bladder cancer.