Ultrasound-targeted microbubble destruction mediated miR-492 inhibitor suppresses the tumorigenesis in non-small cell lung cancer.

BACKGROUND: Ultrasound-targeted microbubble destruction (UTMD) is a novel adjuvant tumor therapeutic method by enhancing exogenous gene transfection to target tissues. This study aims to investigate the role of microRNA-492 (miR-492) in non-small cell lung cancer (NSCLC) and further analyze the effects of UTMD-mediated miR-492 inhibitor on tumorigenesis. METHODS: The expression of miR-492 was detected by qRT-PCR. Co-transfection of microbubbles and miR-492 inhibitor with Lipofectamine 3000 was performed to achieve UTMD-mediated miR-492 inhibition in NSCLC cells. CCK-8 and Transwell assay were used to determine NSCLC cell proliferation, and the migration and invasion. RESULT: High expression of miR-492 was associated with poor prognosis in NSCLC patients. miR-492 inhibitor suppressed tumor cell proliferation, migration and invasion, and UTMD not only increased the transfection efficiency of miR-492 inhibitor, but also enhance the inhibitory effects on cell biological behaviors. CONCLUSION: The results showed that the expression level of miR-492 was up-regulated in NSCLC tissue samples and cells. Silencing of miR-492 inhibited NSCLC cell proliferation, migration and invasion, and UTMD-mediated miR-492 inhibitor could promote more significant inhibition, which indicated that UTMD-mediated miR-492 inhibitor might provide a novel strategy for the treatment of NSCLC.KEY MESSAGESmiR-492 inhibitor inhibited cell proliferation, migration and invasion.UTMD-mediated miR-492 inhibitor can promote more significant inhibition.UTMD-mediated miR-492 inhibitor provide a new strategy for NSCLC.

Site-Specific Variation in Familial Cancer as Suggested by Family History, Multiple Primary Cancer, Age at Onset, and Sex Ratio Associated With Upper, Middle, and Lower Third Esophageal and Gastric Cardia Carcinoma.

BACKGROUND: In China, esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) differ in terms of multiple primary cancer (MPC) and male-to-female sex ratio (MFSR). METHODS: We studied site-specific variation in familial cancer by comparing family history (FH), MPC, age at onset (AO), and MFSR among 8768 patients with ESCC/GCA. RESULTS: ESCC/GCA patients with a positive FH are associated with a significantly higher rate of MPC and a younger AO than those without (sex-specifically: MPC 1.6% vs. 0.7%, P<0.01 and 3.2% vs. 0.8%, P<0.01; AO 53.1 ± 8.1 vs. 54.5 ± 8.2, P=0.000 and 52.9 ± 7.4 vs. 54.0 ± 8.0, P=0.005). Among patients with a positive FH, MPC decreases significantly from upper-, middle-, and lower-third ESCC to GCA (sex-specifically: 53.6%, 1.8%, 1.6%, 0.8%, P=0.000; and 71.4%, 1.5%, 2.2%, 1.6%, P=0.000). From MPC, upper-, middle-, and lower-third ESCC to GCA, AO increased sex-specifically: 51.9 ± 7.2, 52.8 ± 7.9, 52.1 ± 8.3, 54.3 ± 8.4, 55.6 ± 7.6 (P=0.000) and 49.3 ± 6.5, 51.8 ± 9.8, 52.6 ± 7.8, 54.4 ± 8.0, 55.7 ± 7.2 (P=0.000), and FH decreased: 43.8%, 35.1%, 28.2%, 29.5%, 24.4% (P=0.000) and 55.2%, 26.7%, 25.0%, 24.3%, 22.3% (P=0.000). The preponderance of males, smoking, alcohol consumption, and patients ≥50 years old increased from 2.2:1, 1.7:1, 1.0:1, 2.0:1 in ESCC to 6.1:1, 2.8:1, 2.5:1, 4.0:1 in GCA, yet more MPCs were associated with non-preponderant than preponderant counterparts; particularly in GCA, the difference was statistically significant. CONCLUSION: The proportion of familial cancer may decrease from upper-, middle-, and lower-third ESCC to GCA. This entails molecular investigation, and appreciating this may help us devise a better screening strategy or individualize cancer treatment.

Urban-rural disparity in colorectal cancer incidence and increasing trend in relation to socioeconomic development and urbanization in China.

Objective To study urban-rural disparity in colorectal cancer incidence and the increasing trend in relation to rapid socioeconomic development and urbanization in China. Methods We compared the age-standardized incidence rates (ASRs) of colorectal cancer between rural and urban areas in China in 2012 and analyzed the trend in Shexian County for 2000-2015 using population-based tumor registration data collected in Shijiazhuang city (2012) and Shexian County (2000-2015). Results The ASRs of colorectal cancer in Shijiazhuang (urban) were considerably higher than in Shexian (rural) in both men (22.8 vs. 11.9/100,000) and women (15.0 vs. 9.3/100,000). The difference was similar to that between countries with high and medium human development indices according to GLOBOCAN 2012. In trend analysis, the biennial ASR in Shexian increased from 6.6 in 2000-2001 to 15.9/100,000 in 2014-2015 in men (averaged biennial percent change (ABPC) = +6.0%), and from 4.0 to 11.7/100,000 in women (ABPC=+5.5%). Conclusions The incidence of colorectal cancer in China is rising in parallel with socioeconomic development and urbanization. Integrated efforts should be made to reduce the incidences of overweight and obesity in society to help prevent this increase.

Clustering and geographic variation of upper gastrointestinal cancers in a high-risk region of esophageal cancer in northern China.

AIM: Geographic variation of upper gastrointestinal carcinomas (UGIC) was assessed in a high-risk region in northern China. METHODS: Shexian, Linzhou, Yangcheng and Cixian are four counties with world age-standardized incidence rates (ASR) of esophageal cancer as high as 124.9, 99.5, 160.1, and 164.9 per 100,000 respectively for males, and 70.8, 68.8, 92.1, and 104.6 for females for 1998 to 2002. Geographically, Shexian is entirely mountainous, Linzhou and Yangcheng are mostly mountainous, and Cixian is one-third mountains, one-third hills, and the other third plains. The corresponding populations is 382,000, 982,000, 395,000 and 625,000 as in 2000. In the present analyses, the world ASRs of esophageal squamous cell carcinoma (ESCC), adenocarcinoma of the esophagogastric junction (AEG), gastric non-cardia carcinoma (GNCC), and the percentages of these in overall tumor ASRs for 1998 to 2002 were compared across the four counties to show geographic variation and clustering. Additionally, site-specific detection rates of precursors and cancers in our population-based endoscope surveys with local 40- to 69-year-old residents were also compared between a Cixian commune (2,013 surveyed) and a Shexian commune (1,514). RESULTS: ASRs for ESCC, AEG, and GNCC combined amount to 210.5 to 325.8 per 100,000 in men and 117.5 to 185.7 in women, accounting for respectively 70.6 to 82.1% and 53.4 to 77.0 % of the all ASRs. In geographic distribution, the percentages of AEG and GNCC in UGICs increased from Cixian (males 32.8%, females 22.1%) to Yangcheng (50.7%, 38.6%) and Linzhou (52.7%, 41.4%), and further to Shexian (61.7% , 61.9); while that of ESCC decreased in the same direction from Cixian, to Yangcheng and Linzhou, and further to Shexian (67.2% , 77.9% ; 49.3% , 61.4% and 47.3%, 58.6% ; to 38.3% , 38.1%). Similarly, the detection rates of low- and high-grade intraepithelia neoplasia as well as cancers of the esophagus were significantly higher in the Cixian commune than the Shexian commune (8.7, 4.4, 0.7% vs 7.0, 3.2, 0.4% P=0.004 ); but the rates for the esophagogastric junction were systematically and significantly lower in the Cixian than in the Shexian commune (2.2, 0.5, 0.8 % Vs 3.3, 0.9, 1.7 %, P=0.001). CONCLUSIONS: Clustering of upper gastrointestinal carcinomas may suggest the existence of common risk factors, while geographic variation in topography/histology may be related to regional differences in carcinogen exposure. These observations identify a need for environment improvement, such as programs to improve drinking water conditions. To study high susceptibility in a historically low mobile population, international collaborative research in this region may prove to be very fruitful.