Tumor relapse after radiotherapy is a significant challenge to oncologists, even after recent the advances in technologies. Here, we showed that cancer-associated fibroblasts (CAFs), a major component of cancer stromal cells, promoted irradiated cancer cell recovery and tumor relapse after radiotherapy. We provided evidence that CAFs-produced IGF1/2, CXCL12 and β-hydroxybutyrate were capable of inducing autophagy in cancer cells post-radiation and promoting cancer cell recovery from radiation-induced damage in vitro and in vivo in mice. These CAF-derived molecules increased the level of reactive oxygen species (ROS) post-radiation, which enhanced PP2A activity, repressing mTOR activation and increasing autophagy in cancer cells. Consistently, the IGF2 neutralizing antibody and the autophagy inhibitor 3-MA reduce the CAF-promoted tumor relapse in mice after radiotherapy. Taken together, our findings demonstrated that CAFs promoted irradiated cancer cell recovery and tumor regrowth post-radiation, suggesting that targeting the autophagy pathway in tumor cells may be a promising therapeutic strategy for radiotherapy sensitization.

ObjectiveTo assess whether pre-pregnancy body mass index (BMI) modify the relationship between gestational weight gain (GWG) and child birth weight (specifically, presence or absence of low birth weight (LBW) or presence of absence of macrosomia), and estimates of the relative risk of macrosomia and LBW based on pre-pregnancy BMI were controlled in Wuhan, China.MethodsFrom June 30, 2011 to June 30, 2013. All data was collected and available from the perinatal health care system. Logistic regression models were used to estimate the independent association among pregnancy weight gain, LBW, normal birth weight, and macrosomia within different pre-pregnancy BMI groups. We built different logistic models for the 2009 Institute of Medicine (IOM) Guidelines and Chinese-recommended GWG which was made from this sample. The Chinese-recommended GWG was derived from the quartile values (25th-75th percentiles) of weight gain at the time of delivery in the subjects which comprised our sample.ResultsFor LBW children, using the recommended weight gain of the IOM and Chinese women as a reference, the OR for a pregnancy weight gain below recommendations resulted in a positive relationship for lean and normal weight women, but not for overweight and obese women. For macrosomia, considering the IOM’s recommended weight gain as a reference, the OR magnitude for pregnancy weight gain above recommendations resulted in a positive correlation for all women. The OR for a pregnancy weight gain below recommendations resulted in a negative relationship for normal BMI and lean women, but not for overweight and obese women based on the IOM recommendations, significant based on the recommended pregnancy weight gain for Chinese women. Of normal weight children, 56.6% were above the GWG based on IOM recommendations, but 26.97% of normal weight children were above the GWG based on Chinese recommendations.ConclusionsA GWG above IOM recommendations might not be helpful for Chinese women. We need unified criteria to classify adult BMI and to expand the sample size to improve representation and to elucidate the relationship between GWG and related outcomes for developing a Chinese GWG recommendation.

Maternal exposure to ambient air pollution has increasingly been linked to congenital heart defects (CHDs). The objective of this study was to evaluate whether high levels of maternal exposure to PM2.5 and PM10 are related to increased risk of CHDs in Wuhan, China. We conducted a cohort study with a total of 105,988 live-born infants, stillbirths, and fetal deaths. The study included mothers living in the urban district of Wuhan during pregnancy over the 2-year period from 10 June 2011 to 9 June 2013. For each study participant, we assigned 1-month and 1-week averages of PM10 and PM2.5 exposure based on measurements obtained from the nearest exposure monitor to the living residence of mothers during their early pregnancy period. Logistic regression analyses were conducted to calculate the adjusted odds ratios (aORs) and 95% confidence intervals (CI) for the association between exposure to these ambient air pollutants during early pregnancy and CHDs. We observed an increased risk of CHDs, particularly ventricular septal defect (VSD), with increasing PM2.5 exposure. Using 1-week averages, we also observed significant monotonically increasing associations between PM2.5 exposure during weeks 7–10 of pregnancy and risk of VSD, with aORs ranging from 1.11 to 1.17 (95% CI: 1.02–1.20, 1.03–1.22, 1.05–1.24, and 1.08–1.26 separately) per a 10 μg/m3 change in PM2.5 concentration. Our study contributes to the small body of knowledge regarding the association between in utero exposure to air pollution and CHDs, but confirmation of these associations will be needed in future studies.

Background/Aims: Lung adenocarcinoma, a form of non-small cell lung cancer with high lethality at an advanced stage, is becoming more common in women, non- or never-smokers, and even young adults. At present, there are still no effective early diagnosis methods for patients to be cured in a timely manner. Circular RNAs (circRNAs), which are stable and conserved non-coding RNA in mammalian cells, have been reported to be widely involved in the processes of cancer disease. However, it is still a puzzle as to which specific circRNAs are involved in the development of early-stage lung adenocarcinoma. Methods: Tumor samples and paired adjacent normal tissues from 4 patients with early-stage lung adenocarcinoma were selected to investigate the expression profile of circRNAs by using a high-throughput circRNA microarray. Bioinformatic analyses were conducted to screen those differentially expressed circRNAs. qRT-PCR and sequencing were performed to assure the microarray data. Results: A total of 357 circRNAs were dysregulated in the tumor samples, which suggests potential roles in lung cancer. qRT-PCR detection showed that five selected circRNAs were identical to the microarray data, and the potential circRNA-miRNA interactions were predicted. Conclusion: This work illustrates that clusters of circRNAs are aberrantly expressed in early-stage lung adenocarcinoma, which might offer potential targets for the early diagnosis of this disease and new genetic insights into lung cancer.

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