The relation between self-reported physician-diagnosed asthma and/or hay fever and cancer mortality was explored in a prospective cohort study of 1,102,247 US men and women who were cancer-free at baseline. During 18 years of follow-up, from 1982 to 2000, there were 81,114 cancer deaths. Cox proportional hazards models were used to obtain adjusted relative risks for all cancer mortality and for cancer mortality at 12 sites associated with allergy indicators. There were significant inverse associations between a history of both asthma and hay fever and overall cancer mortality (relative risk (RR) = 0.88, 95% confidence interval (CI): 0.83, 0.93) and colorectal cancer mortality (RR = 0.76, 95% CI: 0.64, 0.91) in comparison with persons with neither of these allergic conditions. A history of hay fever only was associated with a significantly lowered risk of pancreatic cancer mortality, and a history of asthma only was associated with a significantly lowered risk of leukemia mortality. In never smokers, these associations persisted but were no longer significant. Results for mortality from cancer at other sites were less consistent. Collectively, these results suggest an inverse association between a history of allergy and cancer mortality; however, the strength of evidence for this association is limited.

Cancer stem cells (CSCs) are highly implicated in the progression of human cancers. Thus, targeting CSCs may be a promising strategy for cancer therapy. Wnt/β-catenin and Sonic Hedgehog pathways play an important regulatory role in maintaining CSC characteristics. Natural compounds, such as curcumin, possess chemopreventive properties. However, the interventional effect of curcumin on lung CSCs has not been clarified. In the present study, tumorsphere formation assay was used to enrich lung CSCs from A549 and H1299 cells. We showed that the levels of lung CSC markers (CD133, CD44, ALDHA1, Nanog and Oct4) and the number of CD133-positive cells were significantly elevated in the sphere-forming cells. We further illustrated that curcumin efficiently abolished lung CSC traits, as evidenced by reduced tumorsphere formation, reduced number of CD133-positive cells, decreased expression levels of lung CSC markers, as well as proliferation inhibition and apoptosis induction. Moreover, we demonstrated that curcumin suppressed the activation of both Wnt/β-catenin and Sonic Hedgehog pathways. Taken together, our data suggested that curcumin exhibited its interventional effect on lung CSCs via inhibition of Wnt/β-catenin and Sonic Hedgehog pathways. These novel findings could provide new insights into the potential therapeutic application of curcumin in lung CSC elimination and cancer intervention. Copyright © 2017 John Wiley & Sons, Ltd.

Highlights d NF1 is a GAP-independent estrogen receptor transcription co-repressor d Somatic NF1 loss causes tamoxifen/aromatase inhibitor resistance in ER + breast cancer d A MEK inhibitor plus a SERD is effective in NF1 -ER + PDX and cell line models

The beneficial effects of tea consumption on cancer prevention have been generally reported, while (−)-Epigallocatechin-3-gallate (EGCG) is the major active component from green tea. Cancer stem cells (CSCs) play a crucial role in the process of cancer development. Targeting CSCs may be an effective way for cancer intervention. However, the effects of EGCG on colorectal CSCs and the underlying mechanisms remain unclear. Spheroid formation assay was used to enrich colorectal CSCs from colorectal cancer cell lines. Immunoblotting analysis and quantitative real-time polymerase chain reaction were used to measure the alterations of critical molecules expression. Immunofluorescence staining analysis was also used to determine the expression of CD133. We revealed that EGCG inhibited the spheroid formation capability of colorectal cancer cells as well as the expression of colorectal CSC markers, along with suppression of cell proliferation and induction of apoptosis. Moreover, we illustrated that EGCG downregulated the activation of Wnt/β-catenin pathway, while upregulation of Wnt/β-catenin diminished the inhibitory effects of EGCG on colorectal CSCs. Taken together, this study suggested that EGCG could be an effective natural compound targeting colorectal CSCs through suppression of Wnt/β-catenin pathway, and thus may be a promising agent for colorectal cancer intervention.

Butyrate is an inhibitor of histone deacetylase (HDAC) and has been extensively evaluated as a chemoprevention agent for colon cancer. We recently showed that mutations in the adenomatous polyposis coli (APC) gene confer resistance to HDAC inhibitor-induced apoptosis in colon cancers. Here, we show that APC mutation rendered colon cancer cells resistant to butyrate-induced apoptosis due to the failure of butyrate to down-regulate survivin in these cells. Another cancer-preventive agent, 3,3′-diindolylmethane (DIM), was identified to be able to down-regulate survivin in colon cancers expressing mutant APC. DIM inhibited survivin mRNA expression and promoted survivin protein degradation through inhibition of p34 cdc2 -cyclin B1-mediated survivin Thr 34 phosphorylation. Pretreatment with DIM enhanced butyrate-induced apoptosis in colon cancer cells expressing mutant APC. DIM/ butyrate combination treatment induced the expression of proapoptotic Bax and Bak proteins, triggered Bax dimerization/activation, and caused release of cytochrome c and Smac proteins from mitochondria. Whereas overexpression of survivin blocked DIM/butyrateinduced apoptosis, knocking down of survivin by small interfering RNA increased butyrateinduced apoptosis in colon cancer cells. We further showed that DIM was able to downregulate survivin and enhance the effects of butyrate in apoptosis induction and prevention of familial adenomatous polyposis in APC min/+ mice. Thus, the combination of DIM and butyrate is potentially an effective strategy for the prevention of colon cancer.