No abstract

Derlin-1 is overexpressed in various types of solid tumors and has an important function in cancer progression. However, its expression pattern in and association with the clinicopathological characteristics of human bladder cancer remain unclear. In the present study, 3 pairs of fresh samples of bladder cancer tissue and paracancerous tissue were first detected by liquid chromatography tandem mass spectrometry (UPLC-MS/MS) to screen for differentially expressed proteins. Following bioinformatics analysis and assessments by qRT-PCR and western blotting, Derlin-1 was selected as a candidate protein and was then validated in samples from patients with bladder cancer by immunohistochemistry and western blotting. The results showed that the bladder cancer tissues exhibited higher levels of Derlin-1 expression than the paracancerous tissues (P < 0.05). Positive expression of Derlin-1 was significantly correlated with tumor stage, histological grade, and lymph node metastasis (P < 0.001) but was not correlated with other clinicopathological parameters including patient age (P = 0.758) and gender (P = 0.831). Besides, Derlin-1 was highly expressed in BC cell lines (um-uc-3 and T24), and the interference of Derlin-1 could reverse EMT progression, inhibit the tumor migration and invasion in T24 cells. Further, patients with positive Derlin-1 expression had shorter overall survival than those with negative expression (P < 0.001). Taken together, our results demonstrated that Derlin-1 was overexpressed in bladder cancer and was associated with the malignancy of bladder cancer.

Currently, arsenic has been clinically investigated as a therapeutic agent for a variety of solid malignancies, including breast cancer. However, the exact underlying molecular mechanisms through which arsenic trioxide (As(2)O(3)) induces cell growth arrest and apoptosis in solid tumors have not been clearly understood. The aim of our study was to gain an insight into the effect of As(2)O(3) on the human breast cancer MCF-7 cell line and investigate cell growth inhibition, apoptosis, and the molecular mechanism after As(2)O(3) treatment in MCF-7 cells. Expression of FOXO3a, nuclear-FOXO3a, caspase-3, and IκB kinase β (IKKβ) mRNA levels in MCF-7 cells was determined by reverse transcription-polymerase chain reaction (RT-PCR). The protein expression was examined by the Western blot analysis and immunocytochemical staining. The distribution of apoptotic cells was assessed by flow cytometry, and the morphology of the apoptotic cells was investigated by Hoechest33258 staining. Our results showed that As(2)O(3) significantly induced the apoptosis of MCF-7 cells tested in this study in a dose-dependent manner. As(2)O(3) induced the decrease of IKKβ expression and the increase of total as well as nuclear FOXO3a expression, which triggered the phosphorylation of cytoplasmic FOXO3a at the Thr32 residue decrease. RT-PCR, Western blot analysis, and immunocytochemistry revealed that the expression of IKKβ in MCF-7 cells was upregulated when As(2)O(3) was combined with tumor necrosis factor-α (TNF-α), whereas the expression of FOXO3a was downregulated in comparison with the As(2)O(3)-alone group. These findings indicated a specific molecular mechanism by which MCF-7 cell lines were susceptible to the As(2)O(3) therapy through FOXO3a expression and localization. This FOXO3a accumulation may be well correlated with the As(2)O(3)-induced reduction of active IKKβ, which may provide new insights into As(2)O(3)-related signaling activities.

The eukaryotic chaperonin family is vital for cell survival. The dysregulation of chaperonin-containing TCP-1 subunit 3 (CCT3) is implicated in several types of malignant tumors' development. However, its functional role in melanoma remains unknown. Here we elucidate the functional contribution to CCT3 to melanoma progression. The results indicated that CCT3 highly expressed in melanoma tissues, and CCT3 overexpression is correlated with clinical stage in melanoma patients. Knockdown of CCT3 by shRNA in melanoma cells inhibited cell proliferation and cell cycle progression and induced cell apoptosis in vitro. In vivo, tumor growth in the nude mice was significantly inhibited after CCT3 silencing. Importantly, the gene array analysis showed that CCT3 depletions inhibited cyclins and cell cycle regulation signaling and further evaluation demonstrated that CDK1 expression was significantly decreased after CCT3 knockdown. Additionally, Functional rescues experiments also indicated that decreased cell proliferation due to CCT3 silencing was rescued by CDK1 overexpression. Overall, our findings suggest that CCT3 depletions prohibited melanoma progression by downregulating CDK1 expression and is a potential therapeutic target for melanoma.

The radiation-induced carcinogenesis from computed tomography (CT) and iodine contrast agent induced nephropathy has attracted international attention. The reduction of the radiation dose and iodine intake in CT scan is always a direction for researchers to strive. The purpose of this study was to evaluate the feasibility of a “double-low” (i.e., low tube voltage and low-dose iodine contrast agent) scanning protocol for dynamic hepatic CT with the adaptive statistical iterative reconstruction (ASIR) in patients with a body mass index (BMI) of 18.5 to 27.9 kg/m2.A total of 128 consecutive patients with a BMI between 18.5 and 27.9 kg/m2 were randomly assigned into 3 groups according to tube voltage, iodine contrast agent, and reconstruction algorithms. Group A (the “double-low” protocol): 100 kVp tube voltage with 40% ASIR, iodixanol at 270 mg I/mL, group B: 120 kVp tube voltage with filtered back projection (FBP), iodixanol at 270 mg I/ mL, and group C: 120 kVp tube voltage with FBP, ioversol at 350 mg I/ mL.The volume CT dose index (CTDIvol) and effective dose (ED) in group A were lower than those in group B and C (all P < 0.01). The iodine intake in group A was decreased by approximately 26.5% than group C, whereas no statistical difference was observed between group A and B (P > 0.05). There was no significant difference of the CT values between group A and C (P > 0.05), which both showed higher CT values than that in group B (P < 0.001). However, no statistic difference was observed in the contrast-to-noise ratio (CNR), the signal-to-noise ratio (SNR), and image-quality scores among the 3 groups (all P > 0.05). Near-perfect consistency of the evaluation for group A, B, and C (Kenall's W = 0.921, 0.874, and 0.949, respectively) was obtained by the 4 readers with respect to the overall image quality.These results suggested that the “double-low” protocol with ASIR algorithm for multi-phase hepatic CT scan can dramatically decrease radiation dose and iodine intake with adequate image quality in patients with BMI of 18.5 to 27.9 kg/m2.