Gallbladder cancer is a highly aggressive malignancy with a low 5‐year survival rate. Despite advances in the molecular understanding of the initiation and progression in gallbladder cancer, treatment modalities such as surgery, radiotherapy, or chemotherapy in advanced cases did not yield promising outcomes. Therefore, it is of great importance to uncover new mechanism underlying gallbladder cancer growth and metastasis. In this study, we identified a differentially expressed long intergenic non‐coding RNA , linc‐ ITGB 1, in a pair of higher and lower metastatic gallbladder cancer cell sublines. Then, the potential role of linc‐ ITGB 1 in gallbladder cancer cell proliferation, migration, and invasion was explored using a lentivirus‐mediated RNA interference system. Functional analysis showed that knockdown of linc‐ ITGB 1 significantly inhibited gallbladder cancer cell proliferation. Moreover, cell migration and invasion were reduced by over twofold in linc‐ ITGB 1 knockdown cells probably due to upregulation of β ‐catenin and downregulation of vimentin, slug, and TCF 8. In conclusion, linc‐ ITGB 1 potentially promoted gallbladder cancer invasion and metastasis by accelerating the process of epithelial‐to‐mesenchymal transition, and the application of RNA interference targeting linc‐ ITGB 1 might be a potential form of gallbladder cancer treatment in advanced cases.
In this era of information explosion, software with various functions is emerging and the harm that software vulnerabilities can cause is increasing.Coverage-based greybox fuzzing (CGF) is already known as one of the most effective software vulnerability detection methods available, due to its simple principle and excellent results.However, the mutator is blind to the exploration of undiscovered paths, it cannot know how to search the input space to explore new paths, and can only mutate all input bytes or random bytes in an attempt to search for new paths.In this paper, we propose a method based on the dynamic construction of control flow graph to guide the mutation direction of the fuzzing.Based on the explored control flow information, we can analyze where still unexplored basic blocks remain and combine with input branch dependency analysis to mutate toward unexplored paths.We implemented a prototype DGFuzz and benchmarked it against four other state-of-the-art fuzzers.The evaluation results show that DGFuzz can discover more new branches than other fuzzers.
To evaluate the psychological status of early-stage breast cancer outpatients using the Kessler 10 Scale (K10) and to determine the feasibility of employing the K10 scale for psychological assessment in outpatient settings. This cross-sectional study surveyed 250 patients at the Breast Surgery Outpatient Clinic of our hospital, from February to March 2023, using the Kessler 10 Scale (K10) questionnaire. A total of 120 breast cancer (BC) patients and 120 non-breast cancer (non-BC) patients completed the questionnaire. The K10 scores were significantly higher in BC patients compared to non-BC patients (15 [12.25, 20] vs. 13.5 [11.25, 17], P = 0.006). Among BC patients, those receiving postoperative endocrine therapy had significantly higher K10 scores than those not (19 [14, 22] vs. 15 [12, 20], P = 0.04). However, the type of surgery did not significantly impact the psychological status of BC patients (P = 0.57). The Kessler 10 Scale (K10) is a practical tool for initial psychological screening in outpatient settings. BC patients demonstrate significantly higher levels of psychological distress compared to non-BC patients. Patients undergoing endocrine therapy as part of adjuvant treatment following surgery experience greater psychological distress compared to those not. These findings underscore the importance of early psychological monitoring and intervention for this population during outpatient visits.
Gamma glutamylcyclotransferase (GGCT) has been proved to be involved in various cancers, but the biological function of GGCT in gastric cancer is still largely unknown. The expression level of GGCT was evaluated by informatics analyses based on the Oncomine database. GGCT gene was then effectively knocked down via lentivirus mediated short hairpin RNA (shRNA) system. Then a series of functional assays, including MTT, colony formation and flow cytometry analysis were conducted on gastric cancer cells following GGCT knockdown. We found GGCT is commonly up-regulated in gastric cancer tissues. Furthermore, MTT analysis showed that GGCT depletion significantly inhibited cell proliferation in MGC80-3 and AGS cells. Colony formation assay revealed that depletion of GGCT reduced the colony formation ability in gastric cancer cells. What's more, cell cycle analysis showed that depletion of GGCT induced gastric cancer cell cycle arrested G2/M phase. More importantly, cell apoptosis analysis further revealed that GGCT inhibition induced early and late cell apoptosis in gastric cancer. This study suggests GGCT is essential for gastric cancer proliferation and its downregulation may provide a potential anticancer therapy for gastric cancer.
Bromodomain containing protein 4 (BRD4) has been demonstrated to play a critical role in tumor progression. However, the expression and function of BRD4 in gallbladder cancer (GBC) are still unknown. In this study, we report that BRD4 expression level was significantly upregulated in GBC tissues and GBC cell lines. We explored the correlation between BRD4 levels and clinicopathological data of GBC patients. The high expression level of BRD4 was notably correlated with the poor prognosis of GBC patients. Knockdown of BRD4 suppressed proliferation and migration in NOZ and EH-GB1 cells. The depletion of BRD4 in GBC cell lines resulted in obvious cell apoptosis and downregulated the expression levels of Bcl-2, p-PI3K and p-AKT. In vivo, tumor volumes of nude mice were significantly decreased in BRD4 silenced group. Our data suggested that downregulation of BRD4 in GBC cells induced apoptosis by PI3K/AKT pathway. Inhibition of BRD4 expression may be a novel therapeutic strategy for patients with GBC.
Gallbladder cancer (GBC) is one of the mostly aggressive diseases with poor prognosis due to the lack of severe symptoms. To date, little is known about the potential roles and underlying mechanisms of long noncoding RNAs (lncRNAs) in GBC initiation and progression. Thus, it provides us with a novel insight into the contribution of lncRNAs to GBC development. Remarkably, we found the differential expression of a lncRNA, namely, KIAA0125, in a pair of GBC cell sublines which possess different metastatic potentials. Then the effects of KIAA0125 on GBC cell migration, invasion, and epithelial-mesenchymal transitions (EMT) were investigated by using a lentivirus-mediated RNA interference (RNAi) system. Notably, cell migration and invasion were strongly inhibited by KIAA0125 suppression. Moreover, the expression of β -Catenin was increased and the expression of Vimentin was decreased in GBC-SD/M cells after KIAA0125 knockdown. Thus, our findings suggested that KIAA0125 promoted the migration and invasion of GBC cells and could serve as a potential therapeutic target in advanced GBC.
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