ABSTRACT
BACKGROUND: Most patients with non-muscle invasive bladder cancer (NMIBC) have a high direction for recurrence and disease progression, which remains a significant unresolved challenge in bladder cancer patients. Therefore, a constant search is necessary for identifying appropriate and reliable biomarkers for early diagnosis of NMIBC. The current study has aimed to search for valuable diagnostic biomarkers in the tissue and urine specimens of NMIBC patients. METHODS: The changes of twelve candidate mRNAs in a screening phase (40 tissue samples of NMIBC patients and their corresponding 40 urine specimens) and a subsequent independent validation phase (40 urine specimens) were estimated using real-time polymerase chain reaction (RT-qPCR). The receiver operating characteristic (ROC) analysis was executed to determine the potential diagnostic values of mRNAs. RESULTS: The mRNA levels of seven candidate genes were markedly higher in tissue specimens relative to their neighboring tissues. Among them, four mRNAs, including ERBB2, CCND1, MKI67, and MAGEA6, were differentially expressed in urine samples of NMIBC patients relative to control subjects. Further, the expression of these four mRNAs was validated in the validation step. Combining these biomarkers showed better diagnostic performance than single biomarkers in the urine sample for non-invasive NMIBC detection. The combination of these mRNAs and cytology enhanced the sensitivity of cytology from 37% to 87%. CONCLUSION: Our findings suggested that a four-mRNA panel may be promising in the non-invasive diagnosis of NMIBC, which deserves further investigation.
ABSTRACT
Bladder cancer is one of the concerning urological malignant diseases in the world, which has a clinical need for effective targeted therapy. The development of nanotechnology-based gene delivery to bladder tumor sites is an effective strategy for targeted cancer therapy with low/no toxicity. With this view, in the present work, the mesoporous silica nanoparticles (MSNs) modified with c(RGDfK)-PLGA-PEG [c(RGDfK)-MSN NPs] were constructed for co-delivery of miR-34a and siPD-L1 within bladder cancer cells and tissues. Our findings showed that miR-34a is downregulated while PD-L1 is up-regulated in cell lines and animal studies. This nano-carrier is biocompatible in the serum environment and effectively protects miR-34a and siPD-L1 against serum degradation. However, we showed that c(RGDfK)-MSN NPs could simultaneously downregulate PD-L1 expression and up-regulate miR-34a in the T24 cells and T24 mice model and enhance anti-tumor effects both in vivo and in vitro. In conclusion, these findings presented new suggestions for improving targeted therapeutic strategies with specified molecular objectives for bladder cancer treatment.
ABSTRACT
INTRODUCTION: The study aimed at measuring exhaled breath malondialdehyde (EBC-MDA) in workers exposed to dust containing silica and at its comparison with the non-exposed control group. MATERIAL AND METHODS: The cross sectional, case-control study (N = 50) was performed in a tile and ceramics production factory in Yazd, Iran. EBC-MDA was quantified in exhaled breath of the participants by a lab made breath sampler. Exposure intensity was measured according to the NIOSH 0600 method in selected homogeneous exposure groups. Additionally, spirometry test was conducted to investigate a correlation between EBC-MDA and spirometric findings in the exposed workers. RESULTS: There was no difference in the observed exposure intensities of silica containing dust in different units. However, "coating preparation" was the unit with the highest concentration of dust. Although, the level of EBC-MDA in the cases was slightly higher than in the controls, the difference was not statistically significant (U = 252, p = 0.464). A significant and positive correlation was found between dust exposure intensity in working units and the measured EBC-MDA of workers (r = 0.467, N = 25, p = 0.027). There were also no statistically significant differences among job categories in the exposed group for the values of FEV1% (F(3, 44) = 0.656, p = 0.584), FVC% (F(3, 44) = 1.417, p = 0.172), and FEV1/FVC% (F(3, 44) = 1.929, p = 0.139). CONCLUSIONS: The results showed a significant correlation between respirable dust exposure intensity and the level of EBC-MDA of the exposed subjects. However, our results did not show a significant correlation between lung function decreases and EBC-MDA.