[Lung Cancer Screening Study in Macao Smoking Individuals].

BACKGROUND: Lung cancer incidence in Macao increases gradually, smoking is one of the important high risk factors. The purpose of this study is to observe the detection rate of lung cancer and nodules in long-term smoking Macao individuals. METHODS: We recruited eligible Macao residents by publicity, all subjects were arranged to receive low-dose computed tomography screening. Image features of lung nodules were analyzed by radiologist. For suspicious lung cancer, multiple disciplinary team (MDT) was arranged. RESULTS: A total of 291 were adopted, 10 lung cancers were detected, the detection rate of lung cancer was 3.44% (95%CI: 2.78%-4.01%), all were males. There were 5 adenocarcinoma patients, each 2 squamous-cell carcinoma and small cell lung carcinoma patients; 1 adenosquamous cancer patient. Among 10 lung cancers, 40% had stage 1 disease. The detection rate of lung nodules was 72.9% (95%CI: 67.8%-78.0%); The number of suspicious lung nodules were 44, and the detection rate was 15.1% (95%CI: 11.0%-19.2%). There was no significant differences in the lung cancer detection rate between the single and multiple lung nodule groups (P>0.05). There were 168 subjects in the <6 mm solid lung nodule (SN) and <5 mm no-solid lung nodule (NSN) group and no lung cancer was found, 44 subjects in the ≥6 mm SN and ≥5 mm NSN group. All 9 lung cancer patients were detected in this group. The detection rate of lung cancer was higher than that of the <6 mm SN and <5 mm NSN group (P<0.05). CONCLUSIONS: There are high detection rate of lung cancer and lung nodule in the long-term smoking individuals. The lung cancer rate increases when the lung nodule size is larger than 6 mm in SN and 5 mm in NSN. Adenocarcinoma is the major type in the smokers' lung cancers. We suggest long-term smokers should join in the future lung cancer screening trial in Macao. Female lung cancer screening should be established different standard.

Design, Synthesis and Activity Evaluation of New Phthalazinone PARP Inhibitors.

Poly(ADP-ribose)polymerase (PARP) is a significant therapeutic target for the treatment of numerous human diseases. Olaparib has been approved as a PARP inhibitor. In this paper, a series of new compounds were designed and synthesized with Olaparib as the lead compound. In order to evaluate the inhibitory activities against PARP1 of the synthesized compounds, in vitro PARP1 inhibition assay and intracellular PARylation assay were conducted. The results showed that the inhibitory activities of the derivatives were related to the type of substituent and the length of alkyl chain connecting the aromatic ring. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT)-based assay also proved that these compounds demonstrating strong inhibition to PARP1 also have high anti-proliferative activities against BRCA2-deficient cell line (Capan-1). Analysis of the entire results suggest that compound 23 with desirable inhibitory efficiency may hold promise for further in vivo exploration of PARP inhibition.

Identification of genes and signaling pathways associated with squamous cell carcinoma by bioinformatics analysis.

The present study aimed to investigate the genes and signaling pathways associated with squamous cell carcinoma (SCC) by bioinformatics analysis. For this purpose, the GSE2503 was downloaded from the Gene Expression Omnibus database, and the differentially expressed genes (DEGs) between 6 normal skin and 5 SCC samples were analyzed using the Linear Models for Microarray Data package. Gene Ontology (GO) and pathway enrichment analysis of DEGs were performed, followed by functional annotation and construction of a protein-protein interaction (PPI) network. Subnetwork modules were subsequently identified and analyzed. A total of 181 DEGs, including 95 upregulated and 86 downregulated DEGs, were identified, in addition to 20 GO biological processes terms enriched by upregulated DEGs and 14 enriched by downregulated DEGs. The upregulated DEGs were enriched in 18 pathways, and the downregulated DEGs were enriched in 7 pathways. Following functional annotation, three upregulated transcription factors (TFs), including hypoxia inducible factor 1, alpha subunit (HIF1A), and six downregulated TFs were identified. In the PPI network and subnetwork, matrix metallopeptidase 1 (MMP1), also known as interstitial collagenase, and interleukin 8 (IL8) were the hub genes with the highest degree of connectivity (degree =8). Integrin alpha (ITGA)6 and 2 were enriched in several pathways, including focal adhesion and extracellular matrix-receptor interaction. DEGs of SCC were primarily enriched in pathways associated with cancer and cell adhesion. Therefore, DEGs such as IL8, MMP1, HIF1A, ITGA6 and ITGA2 may be potential targets for the diagnosis and treatment of SCC.