The association between outdoor air pollution and lung cancer risk in seven eastern metropolises of China: Trends in 2006-2014 and sex differences.

There is a positive association between air pollution and lung cancer burden. This study aims to identify and examine lung cancer risks and mortality burdens associated with air pollutants, including PM10, NO2 and SO2, in seven eastern metropolises of China. The study population comprised a population from seven eastern metropolises of China. The yearly average values (YAV, µg/m3) of the PM10, NO2 and SO2 levels were extracted from China Statistical Yearbook (CSYB) for each selected city from 2006 to 2014. Data collected in the China Cancer Registry Annual Report (CCRAR) provide lung cancer incidence and mortality information. A two-level normal random intercept regression model was adopted to analyze the association between the lung cancer rates and individual air pollutant concentration within a five-year moving window of past exposure. The yearly average values of PM10, SO2 and NO2 significantly decreased from 2006 to 2014. Consistently, the male age-adjusted incidence rate (MAIR) and male age-adjusted mortality rate (MAMR) decreased significantly from 2006 to 2014.Air pollutants have a lag effect on lung cancer incidence and mortality for 2-3 years. NO2 has the significant association with MAIR (RR=1.57, 95% CI: 1.19-2.05, p=0.002), MAMR (RR=1.70, 95% CI: 1.32-2.18, p=0.0002) and female age-adjusted mortality rate (FAMR) (RR=1.27, 95% CI: 1.08-1.49, p=0.003). Our findings suggested that air pollutants may be related to the occurrence and mortality of lung cancer. NO2 was significantly associated with the risk of lung cancer, followed by SO2. Air pollutants have the strongest lag effect on the incidence and mortality of lung cancer within 2-3 years.

Inhibitory effect of PI3Kδ inhibitor idelalisib on proliferation of human myeloid leukemia cells and the reversal effect on drug resistance to adriamycin. / PI3Kδ抑制剂idelalisibå¯¹äººé«“ç³»ç™½è¡€ç— ç»†èƒžå¢žæ®–çš„æŠ‘åˆ¶ä½œç”¨åŠå¯¹é˜¿éœ‰ç´ è€è¯æ€§çš„é€†è½¬ä½œç”¨.

OBJECTIVES: To investigate the effect of adriamycin (ADM), idelalisib or ADM and their combination on cell proliferation and intracellular concentration of ADM, and to explore the reversal effect of idelalisib on drug resistance to ADM. METHODS: The K562 and K562/ADM cells were respectively treated with ADM and idelalisib at different concentrations. The 50% inhibitory concentration (IC50) and drug resistance index (RI) of ADM to the 2 kinds of cells were measured by methyl thiazolyl tetrazolium (MTT) assay. Non-cytotoxic dose (cell inhibition rate <5%) of idelalisib in the 2 kinds of cells was determined. Then the K562 and k562/ADM cells were divided into the following groups: a K562 cells + ADM group, a K562 cells + ADM + idelalisib group, a K562/ADM cells + ADM group, and a K562/ADM cells + ADM + idelalisib group. The survival rates, the intracellular ATP levels, and the relative concentration of intracellular ADM were detected by MTT method, ATP bioluminescence assay (ATP-BLA) and flow cytometry (FCM), respectively. RESULTS: The cell survival rates were significantly decreased in a dose-dependent manner when the cells were treated with different doses of ADM (0.001-10.000 mg/L ). The IC50 value of ADM in the K562 and K562/ADM cells were 0.2 mg/L and 1.0 mg/L, respectively. The RI value was 5. The cell survival rates were also significantly decreased in a dose-dependent manner when the cells were treated with different doses of idelalisib (1-50 µmol/L). The non-cytotoxic dose of idelalisib in the K562 and K562/ADM cells were 25 µmol/L and 15 µmol/L, respectively. The cell survival rates in the ADM+ idelalisib group was less than that in the ADM group (P<0.05)；while there was no statistical difference between the ADM+ idelalisib group and the ADM group in the K562 cells (P>0.05). The intracellular ATP level in the K562 cells was about (91.502±0.479) mmol/L, and that in the K562/ADM cells was about (24.311±0.349) mmol/L. The intracellular ATP level in the ADM+ idelalisib group in the K562/ADM cells was less than that in the ADM group (P<0.05); but there was no statistical difference between the ADM + idelalisib group and the ADM group in the K562 cells (P>0.05). The absorption of intracellular ADM in the ADM + idelalisib group in the K562/ADM cells was more than that in the ADM group (P<0.05); but there was no statistical difference in the K562 cells between the 2 groups (P>0.05). The exclusion of intracellular ADM in the ADM + idelalisib group in the K562/ADM cells was less than that in the ADM group (P<0.05 or P<0.01)；but there was no statistical difference in the K562 cells between the 2 groups (P>0.05). CONCLUSIONS: Idelalisib exerts effect on inhibition of the proliferation in myeloid leukemia K562 and K562/ADM cells, which may partially reverse the drug resistance of K562/ADM cells to ADM. The mechanisms for the effect of idelalisib may be related to increasing the accumulation of ADM and inducing the cell apoptosis in the K562 and K562/ADM cells.

Clinicopathological Features, Treatment, and Prognosis in Primary Diffuse Large B Cell Lymphoma of the Breast: A Retrospective Study of 46 Patients.

BACKGROUND Primary lymphoma of the breast is rare, and primary diffuse large B cell lymphoma (DLBCL) of the breast is very rare. This study aimed to identify the clinicopathological characteristics and treatment associated with prognosis in patients with primary DLBCL of the breast. MATERIAL AND METHODS A retrospective study included the clinical and treatment data from 46 women with a histological diagnosis of primary DLBCL. Patients were staged using Ann Arbor staging criteria, overall survival (OS), progression-free survival (PFS), and the international prognostic index (IPI) scores were obtained. Laboratory finding included serum lactate dehydrogenase (LDH), and the immunohistochemistry findings were recorded. RESULTS Patients (n=46), included stage I (n=18), stage II (n=18), stage III (n=3), and stage IV DLBCL (n=9). Treatment included chemotherapy with rituximab (n=16), and radiotherapy (n=12). The median follow-up time was 40.5 months, the 5-year OS rate was 36.2%, and the 5-year PFS rate was 29.1%. Univariate analysis showed that clinical stage, serum LDH, the IPI score, chemotherapy cycles >3, and Bcl-2 and Bcl-6 expression were correlated with the 5-year OS and PFS. Multivariate risk regression analysis showed that the number of chemotherapy cycles (>3) and Bcl-6 expression were independent prognostic factors in primary DLBCL of the breast (P<0.05). CONCLUSIONS A retrospective study of 46 patients with primary DLBCL of the breast showed that >3 cycles of chemotherapy and expression of Bcl-6 resulted in improved OS and PFS. Radiotherapy controlled local tumor recurrence but did not improve the OS and PFS. Rituximab did not improve patient survival.

A positive feedback signaling loop between ATM and the vitamin D receptor is critical for cancer chemoprevention by vitamin D.

Both epidemiologic and laboratory studies have shown the chemopreventive effects of 1α,25-dihydroxyvitamin D(3) (1,25-VD) in tumorigenesis. However, understanding of the molecular mechanism by which 1,25-VD prevents tumorigenesis remains incomplete. In this study, we used an established mouse model of chemical carcinogenesis to investigate how 1,25-VD prevents malignant transformation. In this model, 1,25-VD promoted expression of the DNA repair genes RAD50 and ATM, both of which are critical for mediating the signaling responses to DNA damage. Correspondingly, 1,25-VD protected cells from genotoxic stress and growth inhibition by promoting double-strand break DNA repair. Depletion of the vitamin D receptor (VDR) reduced these genoprotective effects and drove malignant transformation that could not be prevented by 1,25-VD, defining an essential role for VDR in mediating the anticancer effects of 1,25-VD. Notably, genotoxic stress activated ATM and VDR through phosphorylation of VDR. Mutations in VDR at putative ATM phosphorylation sites impaired the ability of ATM to enhance VDR transactivation activity, diminishing 1,25-VD-mediated induction of ATM and RAD50 expression. Together, our findings identify a novel vitamin D-mediated chemopreventive mechanism involving a positive feedback loop between the DNA repair proteins ATM and VDR.