Azacitidine, an inhibitor of DNA methylation, shows therapeutic effects against several malignancies by inducing apoptosis and inhibiting tumor cell proliferation. However, the anti-tumor effects of azacitidine on urinary bladder urothelial carcinoma (UBUC), especially following intravesical instillation (IVI), are not established. Here, UBUC cell lines were used to analyze the in vitro therapeutic effects of azacitidine. Potential signaling pathways were investigated by antibody arrays and Western blotting. The N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced rat UBUC model was used for in vivo quantitative analysis of tumor burden. Azacitidine significantly inhibited DNMT expression in UBUC cell lines and reduced cell viability and clonogenic activity, as determined by MTT and colony formation assays, while also inducing significant cytotoxic effects in the form of increased sub-G1 and Annexin V-PI populations (all p < 0.05). Antibody arrays confirmed the in vitro suppression of TNF-R1 and the induction of TRAIL-R2 and their downstream signaling molecules. TNF-R1 suppression reduced claspin and survivin expression, while TRAIL-R2 activation induced cytochrome C and caspase 3 expression. Rats with BBN-induced bladder cancer had a significantly reduced tumor burden and Ki67 index following IVI of azacitidine (p < 0.01). Our study provides evidence for a reduction in BBN-induced bladder cancer by IVI of azacitidine through alterations in the TRAIL-R2 and TNF-R1 signaling pathways. These findings might provide new insights for further clinical trials.
Background/Aim: Head and neck cancer is a major malignancy worldwide. The treatment strategy for head and neck cancer usually involves radiotherapy. The main side effect of radiotherapy is radiation dermatitis. Thus, determining the most effective topical regimen for the prevention of radiation dermatitis in head and neck cancer patients is a critical issue. Patients and Methods: PRISMA-NMA guidelines were used in this network meta-analysis. We included only randomized control trials. A random effects model was used. Heterogeneity was evaluated by I 2 and Cochran's Q tests. Results: We included a total of 1,304 patients in the network meta-analysis. Among them, olive oil was the only effective regimen when compared with usual care (OR=0.18, 95%CI=0.03-0.95). The I 2 value was 56%. The test of heterogeneity yielded a p-value of 0.10. Conclusion: Olive oil was the most effective regimen for the prevention of radiation dermatitis.Head and neck cancers are a major malignancy worldwide and include nasopharyngeal, oral cavity, oropharyngeal, hypopharyngeal, and laryngeal cancers. The global burden of head and neck cancer has been increasing (1). Treatment strategies for head and neck cancer include radiotherapy, chemotherapy, targeted therapy, immunotherapy, and surgery. Following radiotherapy for head and neck cancer, the most common side effects in cancer survivors are radiation dermatitis and oral mucositis (2).Radiation dermatitis (RD) usually appears within a few weeks after the start of radiation therapy. Despite advances in radiotherapy techniques, skin reactions are still inevitable. Specifically, approximately 85% of radiated patients with head and neck cancer develop moderate to severe skin reactions (3), the severity of which can be evaluated using the Common Terminology Criteria for Adverse Events proposed by National Cancer Institute (NCI-CTCAE) criteria (4) or the Radiation Therapy Oncology Group (RTOG) criteria (5). Early symptoms include generalized erythema, dry desquamation, pruritus, epilation, scaling, dyspigmentation, and hair loss (6). Radiation dermatitis can affect the patient's quality of life. When symptoms are severe, radiation therapy may even need to be interrupted.Because radiation dermatitis may interfere with the course of radiation therapy, it is common in clinical practice to adopt prophylactic interventions prior to the onset of radiation dermatitis; such prophylaxis consists of general skin care measures and topical agents (7, 8). The main topical agents used in clinical practice include topical corticosteroids, trolamine, Aloe vera, sucralfate, or 1453
Background and Objectives: PNU-74654, a Wnt/β-catenin inhibitor, has reported antitumor activities; however, the therapeutic potential of PNU-74654 in hepatocellular carcinoma (HCC) has not been investigated in detail. The aim of this study was to clarify the cytotoxic effects of PNU-74654 against HCC and to uncover its molecular mechanism. Materials and Methods: HepG2 and Huh7 liver cancer cell lines were selected to determine the antitumor properties of PNU-74654. Survival of the liver cancer cells in response to PNU-74654 was assessed by cell viability assays, and the apoptosis effect of PNU-74654 was analyzed by flow cytometry and visualized by Hoechst staining. An oncology array was used to explore the underlying molecular routes of PNU-74654 action in the cells. The migration properties were examined with a wound healing assay, and western blotting was conducted to evaluate protein expression. Results: Treatment with PNU-74654 decreased cell viability and inhibited cell migration. The cell cycle analysis and Hoechst staining revealed an increase in the population of cells at the sub-G1 stage and apoptotic morphological changes in the nucleus. The oncology array identified 84 oncology-related proteins and a suppressed expression of Bcl-xL and survivin. Western blotting showed that PNU-74654 could interfere with cell cycle-related proteins through the NF-κB pathway. Conclusions: PNU-74654 shows antiproliferative and antimigration effects against HepG2 and Huh7 cells, and its antitumor activity may be attributable to its interference in cell cycle regulation and the NF-κB pathway.
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