Cisplatin and photodynamic therapy exert synergistic inhibitory effects on small-cell lung cancer cell viability and xenograft tumor growth.

Lung cancer is the leading cause of cancer death worldwide. Small-cell lung cancer (SCLC) is an aggressive type of lung cancer that shows an overall 5-year survival rate below 10%. Although chemotherapy using cisplatin has been proven effective in SCLC treatment, conventional dose of cisplatin causes adverse side effects. Photodynamic therapy, a form of non-ionizing radiation therapy, is increasingly used alone or in combination with other therapeutics in cancer treatment. Herein, we aimed to address whether low dose cisplatin combination with PDT can effectively induce SCLC cell death by using in vitro cultured human SCLC NCI-H446 cells and in vivo tumor xenograft model. We found that both cisplatin and PDT showed dose-dependent cytotoxic effects in NCI-H446 cells. Importantly, co-treatment with low dose cisplatin (1 µM) and PDT (1.25 J/cm2) synergistically inhibited cell viability and cell migration. We further showed that the combined therapy induced a higher level of intracellular ROS in cultured NCI-H446 cells. Moreover, the synergistic effect by cisplatin and PDT was recapitulated in tumor xenograft as revealed by a more robust increase in the staining of TUNEL (a marker of cell death) and decrease in tumor volume. Taken together, our findings suggest that low dose cisplatin combination with PDT can be an effective therapeutic modality in the treatment of SCLC patients.

Modified Nuss procedure for the treatment of pectus excavatum: Experience of 259 patients.

BACKGROUND: Pectus excavatum is not rare in China. Many treatments for this disease have proved to have many shortcomings. Nuss procedure has been a ground-breaking technology, but it also has some disadvantages. Hence, this study was conducted to review our experience in the use of modified Nuss procedure in our hospital. METHODS: Data from 259 patients suffered from pectus excavatum between August 2020 and August 2021 who were treated with modified Nuss procedure was analyzed retrospectively. RESULT: Age was from 3 to 37 years. The average was 15.54 years. The male was 213 cases and the female was 46 cases. The time patients or their family members found pectus excavatum varied. 10 cases had been repaired previously when patients were admitted in our hospital. The clinical symptoms also varied. Each case had an improvement in Haller index. The average of the postoperative hospitalization was 3.97 days. Most cases were inserted 1 bar. Complication rate was also very low. All patients or their parents or their guardians were satisfied with the appearance of the chest wall after operation. There was no death in the whole observation period. CONCLUSION: From our experience, this modified Nuss procedure have obtained optimistic outcomes with more minimal invasion and low complication rate. This surgical method may be applied to many other hospitals in the future.

circBIRC6 contributes to the development of non-small cell lung cancer via regulating microRNA-217/amyloid beta precursor protein binding protein 2 axis.

BACKGROUND: Circular RNAs (circRNAs) are considered to be important regulators in cancer biology. In this study, we focused on the effect of circRNA baculoviral inhibitor of apoptosis protein (IAP) repeat containing 6 (circBIRC6) on non-small cell lung cancer (NSCLC) progression. METHODS: The NSCLC and adjacent non-tumor tissues were collected at Shanghai Ninth People's Hospital. Quantitative real-time polymerase chain reaction was conducted for assessing the levels of circBIRC6, amyloid beta precursor protein binding protein 2 (APPBP2) messenger RNA (mRNA), baculoviral IAP repeat containing 6 mRNA (BIRC6), and microRNA-217 (miR-217). Western blot assay was adopted for measuring the protein levels of APPBP2, E-cadherin, N-cadherin, and vimentin. Colony formation assay, transwell assay, and flow cytometry analysis were utilized for evaluating cell colony formation, metastasis, and apoptosis. Dualluciferase reporter assay and RNA immunoprecipitation assay were carried out to determine the interaction between miR-217 and circBIRC6 and APPBP2 in NSCLC tissues. The murine xenograft model assay was used to investigate the function of circBIRC6 in tumor formation in vivo. Differences were analyzed via Student's t test or one-way analysis of variance. Pearson's correlation coefficient analysis was used to analyze linear correlation. RESULTS: CircBIRC6 was overexpressed in NSCLC tissues and cells. Knockdown of circBIRC6 repressed the colony formation and metastasis and facilitated apoptosis of NSCLC cells in vitro and restrained tumorigenesis in vivo. Mechanically, circBIRC6 functioned as miR-217 sponge to promote APPBP2 expression in NSCLC cells. MiR-217 inhibition rescued circBIRC6 knockdown-mediated effects on NSCLC cell colony formation, metastasis, and apoptosis. Overexpression of miR-217 inhibited the malignant phenotypes of NSCLC cells, while the effects were abrogated by elevating APPBP2. CONCLUSIONS: CircBIRC6 aggravated NSCLC cell progression by elevating APPBP2 via sponging miR-217, which might provide a fresh perspective on NSCLC therapy.

MicroRNA­92a promotes non­small cell lung cancer cell growth by targeting tumor suppressor gene FBXW7.

MicroRNA (miRNA/miR)­92a has been identified as being significantly downregulated in non­small cell lung cancer (NSCLC) tissues using a miRNA array. However, its biological function and molecular mechanisms in NSCLC have not been fully elucidated. The aim of the present study was to determine the role of miR­92a in NSCLC and the mechanisms by which it affects NSCLC cells. The expression levels of miR­92a in NSCLC tissues and cell lines were analyzed using reverse transcription­quantitative PCR. Cell viability and cell apoptosis were determined using an MTT assay and flow cytometry, respectively. It was observed that miR­92a was significantly upregulated in NSCLC tissues and cell lines. Inhibition of miR­92a significantly suppressed viability of NSCLC cells, with concomitant downregulation of key proliferative genes, such as proliferating cell nuclear antigen and Ki­67. miR­92a downregulation induced apoptosis of NSCLC cells, as evidenced by flow cytometry and apoptosis­related protein detection. Luciferase assays confirmed that miR­92a could directly bind to the 3'­untranslated region of tumor suppressor F­box/WD repeat­containing protein 7 (FBXW7) and suppress its translation. Furthermore, small interfering RNA­mediated FBXW7 inhibition partially attenuated the tumor suppressive effect of an miR­92a inhibitor on NSCLC cells. Collectively, these findings demonstrated that miR­92a might function as an oncogene in NSCLC by regulating FBXW7. In conclusion, miR­92a could serve as a potential therapeutic target in NSCLC treatment.

The roles of ARHGAP10 in the proliferation, migration and invasion of lung cancer cells.

Lung cancer is a leading cause of cancer-related mortalities worldwide. In the present study, a comparison of To determine the roles of ARHGAP10 in the proliferation, migration and invasion of lung cancer cells expression levels between normal lung tissues and lung cancer tissues were compared using immunoblotting, and CCK-8 and Transwell assays. Lung cancer tissues had a decreased ARHGAP10 mRNA expression level compared to the adjacent normal tissues. The ectopic expression of ARHGAP10 significantly suppressed the migration, invasion and proliferation of lung cancer cells. Gene set enrichment analysis revealed that metastasis and Wnt signaling pathways were negatively correlated with ARHGAP10 expression. Immunoblotting analysis revealed that ARHGAP10 overexpression inhibited metastasis [matrix metalloproteinase (MMP)-2, MMP-9 and VEGF] and the expression of Wnt pathway-related proteins (ß-catenin and c-Myc). Moreover, the stimulation effects of lithium chloride, a GSK3ß inhibitor, on the accumulation of ß-catenin were notably suppressed by ARHGAP10 overexpression. Collectively, ARHGAP10 acts to suppress tumor within lung cancer by affecting metastasis and Wnt signaling pathways. The results therefore suggest that ARHGAP10 is a potentially attractive target for the treatment of lung cancer.