Computed Tomography-Guided Percutaneous Radiofrequency Ablation in Older Adults With Early-Stage Peripheral Lung Cancer: A Retrospective Cohort Study.

OBJECTIVES: To evaluate the feasibility, safety, and efficacy of computed tomography(CT)-guided percutaneous radiofrequency ablation (RFA) in medically inoperable older adults with clinical stage I non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We retrospectively reviewed the records of medically inoperable older adults (≥70 years) with clinical stage I NSCLC who underwent percutaneous multi-tined electrode RFA at our institution between January 2014 and December 2018. We analyzed the patients' characteristics, therapy response, survival, as well as the procedure-related complications. RESULTS: Eighteen patients (10 men and 8 women) with a mean age of 75.9 (71-85) years were treated in during the study period. The median tumor size was 25 mm (range, 19-43 mm); 10 and 8 cases involved stage T1 and T2a disease, respectively. The median follow-up duration was 25 (11-45) months. RFA was technically successful for all 18 lesions, with no treatment-related mortality. The disease control rate was 83.3% (15/18 lesions). There were 6 cases of pneumothorax: one symptomatic case requiring thoracic drainage, and five requiring no treatment. Minor complications, including pulmonary infection, chest pain, fever, and cough, were treated within 4 days (range, 1-4 days). The progression-free survival rates were 83.3%, 64.9%, and 51.9% 1, 2, and 3 years, respectively. The corresponding overall survival rates were 92.2%, 81.5%, and 54.3%, respectively. CONCLUSIONS: CT-guided percutaneous RFA is safe and effective in medically inoperable patients with stage I NSCLC and could be an alternative therapeutic strategy, particularly in older adults with early-stage peripheral lung cancer.

Bioinformatical Analysis of Gene Expression Omnibus Database Associates TAF7/CCNB1, TAF7/CCNA2, and GTF2E2/CDC20 Pathways with Glioblastoma Development and Prognosis.

OBJECTIVE: This study bioinformatically analyzed aberrant genes and pathways for associations with glioblastoma development and prognosis. METHODS: The Gene Expression Omnibus (GEO) database was searched and 4 GEO datasets (GSE4290, GSE50161, GSE116520, and GSE90598) were retrieved for limma and RobustRankAggreg package analyses of differentially expressed genes (DEGs) between glioblastoma and normal brain tissues. Functional enrichment analysis was conducted for the main biological functions of these DEGs, whereas the hub genes were identified using the protein-protein interaction network and confirmed for transcriptional and translational levels using the Cancer Genome Atlas, the Genotype-Tissue Expression, and the Human Protein Atlas data. The prognostic values of these hub genes were analyzed using the Chinese Glioma Genome Atlas. Their transcriptional factor regulation network was constructed to assess the roles in glioblastoma development and progression. RESULTS: A total of 473 DEGs (182 upregulated and 291 downregulated) were identified and the hub genes (including CCNB1, CDC20, CCNB2, BUB1, and CCNA2) were shown in module 1 and enriched in the cell cycle or p53 signaling pathway. The highly expressed CCNB1, CDC20, BUB1, and CCNA2 in patients with glioblastoma were associated with poor overall survival, whereas TAF7 could upregulate expression of CCNB1 and CCNA2 and GTF2E2 could upregulate CDC20 expression in glioblastoma. CONCLUSIONS: This study showed several DEGs in glioblastoma, and aberrant expression of their hub genes was associated with glioblastoma pathogenesis and poor prognosis, especially the signaling axes of TAF7/CCNB1, TAF7/CCNA2, and GTF2E2/CDC20.

LncRNA FUNDC2P4 down-regulation promotes epithelial-mesenchymal transition by reducing E-cadherin expression in residual hepatocellular carcinoma after insufficient radiofrequency ablation.

PURPOSE: Hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (RFA) could induce epithelial-mesenchymal transition (EMT) in residual tumours, resulting in rapid and aggressive recurrence. However, the role of EMT-related Long noncoding RNAs (lncRNAs) in residual tumour progression remains unclear. METHODS: Insufficient RFA was simulated in vitro by heating Huh7 cells in water bath at 47 °C, named as Huh7-H. Cell invasion, migration assays and wound healing assay were conducted for functional analysis. Cell proliferation was determined by CCK8 assay. Differential expression profile of EMT-related lncRNAs between Huh7-H and Huh7 was analysed by LncPath human EMT array, and validated by qRT-PCR. Gain/loss-of-function assays of selected lncRNA were conducted by over-expressing or silencing its expression. RESULTS: Huh7-H presented characteristic EMT morphological changes. WB analysis showed significantly decreased E-cadherin in Huh7-H cells. Transwell assays indicated the abilities of Huh7-H cells in migration and invasion were evidently strengthened. A new lncRNA, FUNDC2P4, was identified by LncPath human EMT array to be significantly down-regulated in Huh7-H cells. In vitro studies showed overexpression of FUNDC2P4 inhibited proliferation, invasion and migration potential and up-regulated E-cadherin expression in SMMC-7721 cells, whereas silencing FUNDC2P4 promoted these potentials and down-regulated E-cadherin expression in Huh7 cells. CONCLUSIONS: We explored that lncRNA FUNDC2P4 down-regulation promoted EMT leading to tumour proliferation, invasion and migration by reducing E-cadherin expression in residual HCC after insufficient RFA in vitro. These results suggest that FUNDC2P4 may have potentially therapeutic value for prevention and treatment of HCC recurrence after RFA in the future.

Glypican-3-specific cytotoxic T lymphocytes induced by human leucocyte antigen-A*0201-restricted peptide effectively kill hepatocellular carcinoma cells in vitro.

OBJECTIVE: To investigate potential human leucocyte antigen (HLA)-A2-restricted epitope peptides of glypican-3 (GPC3) and determine the cytotoxicity of peptide-specific cytotoxic T lymphocytes (CTLs) against hepatocellular carcinoma (HCC) cells. METHODS: The potential HLA-A*0201-restricted GPC3 peptides were screened using computer algorithms, T2 cell-binding affinity and stability of peptide/HLA-A*0201 complex assay. The peptide-specific CTLs were generated and their cytotoxicity against GPC3+ SMMC 7721 and HepG2 cells was detected using IFN-γ based enzyme-linked immunospot and lactate dehydrogenase release assays in vitro. RESULTS: A total of six peptides were identified for bindings to HAL-A2 and the GPC3 522-530 and GPC3 229-237 peptides with HLA-A*0201 molecules displayed high binding affinity and stability. The CTLs induced by the GPC3 522-530 or positive control GPC3 144-152 peptide responded to the peptide by producing IFN-γ, which were abrogated by treatment with anti-HLA-A2 antibody. The GPC3 522-530-specific CTLs responded to and killed SMMC 7721 and HepG2 cells, instead of GPC3-silenced SMMC 7721 or HepG2 cells. GPC3 522-530-specific CTLs response to HCC cells was blocked by anti-HLA-A2 antibody. CONCLUSIONS: The GPC3 522-530 peptide contains antigen-determinant and its specific CTLs can effectively kill HCC in a HLA-A2-restricted and peptide-dependent manner. Our findings suggest that this peptide may be valuable for development of therapeutic vaccine.

The metronomic therapy with prednisone, etoposide, and cyclophosphamide reduces the serum levels of VEGF and circulating endothelial cells and improves response rates and progression-free survival in patients with relapsed or refractory non-Hodgkin's lymphoma.

PURPOSE: There is an urgent need for a better strategy in the management of relapsed or refractory non-Hodgkin's lymphoma (NHL). The present study was designed to evaluate the efficacy and safety of the regimen using metronomic prednisone, etoposide, and cyclophosphamide in the treatment of patients with relapsed or refractory NHL, in comparison with conventional salvage chemotherapy. METHODS: Eligible patients were randomized to the test group (n = 23) receiving metronomic prednisone, etoposide, and cyclophosphamide or the control group (n = 21) receiving conventional salvage chemotherapy. The serum levels of circulating endothelial cells (CECs) and vascular endothelial growth factor (VEGF) were measured before and after two cycles of treatment; overall response rate (ORR) and disease control rate (DCR) were evaluated at cycles 2, 4, 6, and 12 months after treatment. RESULTS: After two cycles of treatment, the ORRs of the test and control groups were statistically similar, while the DCR of the test group (87.0 %) was significantly higher than that of the control group (57.1 %). At 12 months after treatment, the ORR and DCR of the test group (47.8 and 69.6 %, respectively) were significantly higher than that of the control group (19.0 and 33.3 %, respectively). The serum CECs and VEGF levels in the test group after treatment were significantly lower than that before treatment or that of the control group. In the patients with ORR and DCR in the test group, the serum CECs and VEGF levels remained relatively low at cycles 2, 4, and 6 and at 12 months after treatment. There was a progression-free survival (PFS) benefit of 6.5 months in the test group, compared with the control group. CONCLUSION: Metronomic chemotherapy with prednisone, etoposide, and cyclophosphamide resulted in higher ORR and DCR, fewer adverse effects, and longer PFS in patients with relapsed or refractory NHL, with significant reduction in serum CECs and VEGF levels.