Person: Drew, David
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Drew
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Drew, David
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Publication ASPirin Intervention for the REDuction of colorectal cancer risk (ASPIRED): a study protocol for a randomized controlled trial(BioMed Central, 2017) Drew, David; Chin, Samantha M.; Gilpin, Katherine K.; Parziale, Melanie; Pond, Emily; Schuck, Madeline M.; Stewart, Kathleen; Flagg, Meaghan; Rawlings, Crystal; Backman, Vadim; Carolan, Peter; Chung, Daniel; Colizzo, Francis; Freedman, Matthew; Gala, Manish; Garber, John; Huttenhower, Curtis; Kedrin, Dmitriy; Khalili, Hamed; Kwon, Douglas S.; Markowitz, Sanford D.; Milne, Ginger L.; Nishioka, Norman; Richter, James; Roy, Hemant K.; Staller, Kyle; Wang, Molin; Chan, AndrewBackground: Although aspirin is recommended for the prevention of colorectal cancer, the specific individuals for whom the benefits outweigh the risks are not clearly defined. Moreover, the precise mechanisms by which aspirin reduces the risk of cancer are unclear. We recently launched the ASPirin Intervention for the REDuction of colorectal cancer risk (ASPIRED) trial to address these uncertainties. Methods/design ASPIRED is a prospective, double-blind, multidose, placebo-controlled, biomarker clinical trial of aspirin use in individuals previously diagnosed with colorectal adenoma. Individuals (n = 180) will be randomized in a 1:1:1 ratio to low-dose (81 mg/day) or standard-dose (325 mg/day) aspirin or placebo. At two study visits, participants will provide lifestyle, dietary and biometric data in addition to urine, saliva and blood specimens. Stool, grossly normal colorectal mucosal biopsies and cytology brushings will be collected during a flexible sigmoidoscopy without bowel preparation. The study will examine the effect of aspirin on urinary prostaglandin metabolites (PGE-M; primary endpoint), plasma inflammatory markers (macrophage inhibitory cytokine-1 (MIC-1)), colonic expression of transcription factor binding (transcription factor 7-like 2 (TCF7L2)), colonocyte gene expression, including hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD) and those that encode Wnt signaling proteins, colonic cellular nanocytology and oral and gut microbial composition and function. Discussion Aspirin may prevent colorectal cancer through multiple, interrelated mechanisms. The ASPIRED trial will scrutinize these pathways and investigate putative mechanistically based risk-stratification biomarkers. Trial registration This protocol is registered with the U.S. National Institutes of Health trial registry, ClinicalTrials.gov, under the identifier NCT02394769. Registered on 16 March 2015. Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1744-z) contains supplementary material, which is available to authorized users.Publication Aspirin Use is Associated With Lower Risk of Barrett’s Esophagus in Women(Nature Publishing Group, 2017) Jovani, Manol; Cao, Yin; Feskanich, Diane; Drew, David; Hur, Chin; Fuchs, Charles S; Jacobson, Brian C; Chan, AndrewObjectives: Barrett’s esophagus (BE) is the only known precursor to esophageal adenocarcinoma. Data examining the association of aspirin with the onset of BE, particularly for women, are scant and conflicting. Methods: We leveraged data from 121,700 women enrolled in the Nurses’ Health Study, a large prospective cohort study, who biennially provided detailed information regarding endoscopy and use of aspirin. We used unconditional logistic regression to obtain multivariable (MV)-adjusted odds ratios (ORs) and 95% confidence intervals (CI) to estimate the risk of BE in regular aspirin users (≥2 times/week) compared to non-regular users. Results: Among 27,881 women who had undergone upper GI endoscopy, we documented 667 BE cases over 18 years of follow-up. Compared to non-regular users, women who regularly used aspirin had a MV-adjusted OR for BE of 0.85 (95%CI: 0.72, 0.99). The corresponding OR was 0.73 (95%CI: 0.56, 0.96) for BE at least 1 cm long. Compared with women who did not use any aspirin, the MV-adjusted OR for any BE was 0.91 (95% CI, 0.69, 1.20) for women taking 0.5-1.5 tablets/week; 0.92 (95%CI 0.76, 1.11) for 2–5 tablets/week; and 0.71 (95%CI 0.55, 0.92) for ≥6 tablets/week (p-trend=0.01). Compared with non-regular users, the MV-adjusted OR for BE risk was 0.90 (95%CI 0.67, 1.20) for women who regularly used aspirin for 1–5 years, 0.84 (95%CI 0.65, 1.09) for 6–10 years, and 0.81 (95%CI 0.67, 0.97) for >10 years (p-trend=0.03). Conclusion: Regular aspirin use was associated with a reduction in the risk of Barrett’s esophagus in women. The reduction in risk appeared related to higher dose and longer duration of use.Publication Aspirin exerts high anti-cancer activity in PIK3CA-mutant colon cancer cells(Impact Journals LLC, 2017) Gu, Mancang; Nakashima, Reiko; Chen, Yang; Li, Wanwan; Shi, Yan; Masugi, Yohei; Hamada, Tsuyoshi; Kosumi, Keisuke; Liu, Li; da Silva, Annacarolina; Nowak, Jonathan; Twombly, Tyler; Du, Chunxia; Koh, Hideo; Li, Wenbin; Meyerhardt, Jeffrey; Wolpin, Brian M.; Giannakis, Marios; Aguirre, Andrew; Bass, Adam; Drew, David; Chan, Andrew; Fuchs, Charles S.; Qian, Zhi Rong; Ogino, ShujiEvidence suggests that nonsteroidal anti-inflammatory drug aspirin (acetylsalicylic acid) may improve patient survival in PIK3CA-mutant colorectal carcinoma, but not in PIK3CA-wild-type carcinoma. However, whether aspirin directly influences the viability of PIK3CA-mutant colon cancer cells is poorly understood. We conducted in vitro experiments to test our hypothesis that the anti-proliferative activity of aspirin might be stronger for PIK3CA-mutant colon cancer cells than for PIK3CA-wild-type colon cancer cells. We measured the anti-proliferative effect of aspirin at physiologic concentrations in seven PIK3CA-mutant and six PIK3CA-wild-type human colon cancer cell lines. After exposure to aspirin, the apoptotic index and cell cycle phase of colon cancer cells were assessed. In addition, the effect of aspirin was examined in parental SW48 cells and SW48 cell clones with individual knock-in PIK3CA mutations of either c.3140A>G (p.H1047R) or c.1633G>A (p.E545K). Aspirin induced greater dose-dependent loss of cell viability in PIK3CA-mutant cells than in PIK3CA-wild-type cells after treatment for 48 and 72 hours. Aspirin treatment also led to higher proportions of apoptotic cells and G0/G1 phase arrest in PIK3CA-mutant cells than in PIK3CA-wild-type cells. Aspirin treatment of isogenic SW48 cells carrying a PIK3CA mutation, either c.3140A>G (p.H1047R) or c.1633G>A (p. E545K), resulted in a more significant loss of cell viability compared to wild-type controls. Our findings indicate that aspirin causes cell cycle arrest, induces apoptosis, and leads to loss of cell viability more profoundly in PIK3CA-mutated colon cancer cells than in PIK3CA-wild-type colon cancer cells. These findings support the use of aspirin to treat patients with PIK3CA-mutant colon cancer.Publication Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals(Springer Science and Business Media LLC, 2021-01-11) Asnicar, Francesco; Berry, Sarah E.; Valdes, Ana M.; Nguyen, Long; Piccinno, Gianmarco; Drew, David; Leeming, Emily; Gibson, Rachel; Le Roy, Caroline; Al Khatib, Haya; Francis, Lucy; Mazidi, Mohsen; Mompeo, Olatz; Valles-Colomer, Mireia; Tett, Adrian; Beghini, Francesco; Dubois, Léonard; Bazzani, Davide; Thomas, Andrew Maltez; Mirzayi, Chloe; Khleborodova, Asya; Oh, Sehyun; Hine, Rachel; Bonnett, Christopher; Capdevila, Joan; Danzanvilliers, Serge; Giordano, Francesca; Geistlinger, Ludwig; Waldron, Levi; Davies, Richard; Hadjigeorgiou, George; Wolf, Jonathan; Ordovás, José M.; Gardner, Christopher D.; Franks, Paul; Chan, Andrew; Huttenhower, Curtis; Spector, Tim D.; Segata, NicolaThe gut microbiome is shaped by diet and influences host metabolism; however, these links are complex and can be unique to each individual. We performed deep metagenomic sequencing of 1,203 gut microbiomes from 1,098 individuals enrolled in the Personalised Responses to Dietary Composition Trial (PREDICT 1) study, whose detailed long-term diet information, as well as hundreds of fasting and same-meal postprandial cardiometabolic blood marker measurements were available. We found many significant associations between microbes and specific nutrients, foods, food groups and general dietary indices, which were driven especially by the presence and diversity of healthy and plant-based foods. Microbial biomarkers of obesity were reproducible across external publicly available cohorts and in agreement with circulating blood metabolites that are indicators of cardiovascular disease risk. While some microbes, such as Prevotella copri and Blastocystis spp., were indicators of favorable postprandial glucose metabolism, overall microbiome composition was predictive for a large panel of cardiometabolic blood markers including fasting and postprandial glycemic, lipemic and inflammatory indices. The panel of intestinal species associated with healthy dietary habits overlapped with those associated with favorable cardiometabolic and postprandial markers, indicating that our large-scale resource can potentially stratify the gut microbiome into generalizable health levels in individuals without clinically manifest disease.