Is a high-risk clinical target volume required? Evaluation of the dosimetric feasibility based on T staging.

Background: Clinical target delineation is a primary focus in the field of radiotherapy. This study aimed to investigate whether high-risk clinical target volume can be removed in nasopharyngeal carcinoma patients with different T stages. Materials and methods: We designed a test plan without the high-risk clinical target volume for 111 nasopharyngeal carcinoma patients and further compared the test plans with the treatment plans in the parameters of planning target volumes and the radiation dose to normal organs. Results: Our data showed that when high-risk clinical target volume was abnegated, target coverage, conformity indices, and homogeneity indices of planning target volumes and doses of normal organs were not influenced in the T4 nasopharyngeal carcinoma patients, and more than 95% of the high-risk planning target volume area could still be covered by the 60 Gy dose line. However, only some T1-3 patients achieved the ideal dose coverage, and even fewer after induction chemotherapy (62.8% vs. 41.2%, p = 0.018). Gross tumor volume was positively correlated with the target coverage of the original high-risk planning target volume in the test-plan (p = 0.0001). Gross tumor volume can be used to predict whether the target coverage of high-risk planning target volume is more than 95% (area under the curve = 0.868). Conclusion: Omitting high risk clinical target volume can be considered in patients with T4 nasopharyngeal carcinoma according to physical evaluations. However, this approach is only suitable for a specific subset of T1-3 patients.

CircKIAA0368 Promotes Proliferation, Migration, and Invasion by Upregulating HOXA10 in Nasopharyngeal Carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) represents a head and neck cancer caused by cancerization of nasal epithelial cells. HOXA10 has been identified to promote proliferation and invasion of NPC cells, but its regulatory mechanism has not been well discussed. Published research work has also pointed out that circular RNAs (circRNAs) could regulate mRNAs to affect NPC tumorigenesis and development. AIM: To explore the roles of HOXA10 and its specific regulatory mechanism regarding circRNAs in NPC. METHODS: Reverse transcription polymerase chain reaction and western blot were applied to test gene expression. Functional assays were used to evaluate changes in NPC cell phenotypes. Mechanism assays were done to verify RNA-RNA or RNA-protein interaction. RESULTS: HOXA10 was highly expressed in NPC tissues and cell lines. Moreover, HOXA10 knockdown could restrict NPC cell proliferation, invasion, migration, and epithelial-mesenchymal transition. CircKIAA0368 was upregulated in NPC cells and could elevate HOXA10 expression by sponging miR-6838-5p. Furthermore, circKIAA0368 was unveiled to competitively bind to p300/CREB-binding protein-associated factor (PCAF) to repress acetylation and degradation of HOXA10 protein. CONCLUSION: CircKIAA0368 upregulates HOXA10 expression via miR-6838-5p and PCAF, consequently promoting NPCcell and tumor growth.

Origin recognition complex subunit 1 regulates cell growth and metastasis in glioma by altering activation of ERK and JNK signaling pathway.

Origin recognition complex subunit 1(ORC1) is reported to be closely associated with the cell cycle. However, studies on the role of ORC1 in glioma remain undefined. The aim of the present study was to determine whether ORC1 affects cell migration, invasion, apoptosis, and proliferation and to explore the possible underlying mechanism. GEO database analysis indicated that ORC1 was significantly upregulated in glioma, while Gene set enrichment analysis (GSEA) analysis indicated that ORC1 primarily regulated the cell cycle and affects apoptotic signaling pathways. Analysis of protein-protein interaction (PPI) and gene ontology (GO) to further study the relevant mechanisms revealed that the function of the interaction between proteins and ORC1 was primarily concentrated in the regulation of cell cycle, and apoptosis played a critical role in the whole PPI network. Western blot assay and RT-PCR assay indicated that ORC1 was significantly upregulated in glioma tissues. Western blot assay and RT-PCR indicated that ORC1 was significantly upregulated in glioma cell lines. Cell migration, invasion, apoptosis, and proliferation were detected using Transwell and wound healing assays, flow cytometry, colony formation, and CCK8, respectively. Furthermore, OCR1 inhibition reduced invasion and migration, promoted cell apoptosis. In addition, OCR1 overexpression promoted cell proliferation and induced G2 phase arrest. Moreover, OCR1 downregulation suppressed activation of the ERK/JNK signaling pathway. The effects of ORC1 on biological processes were reversed by ERK and JNK inhibitors. These results indicate that ORC1 could be a novel prognostic marker of glioma via the activation of the ERK/JNK signaling pathway.