BackgroundCurcumin is the major yellow pigment extracted from turmeric, a commonly-used spice in India and Southeast Asia that has broad anticarcinogenic and cancer chemopreventive potential. However, few systematic studies of curcumin's pharmacology and toxicology in humans have been performed.MethodsA dose escalation study was conducted to determine the maximum tolerated dose and safety of a single dose of standardized powder extract, uniformly milled curcumin (C3 Complex™, Sabinsa Corporation). Healthy volunteers were administered escalating doses from 500 to 12,000 mg.ResultsSeven of twenty-four subjects (30%) experienced only minimal toxicity that did not appear to be dose-related. No curcumin was detected in the serum of subjects administered 500, 1,000, 2,000, 4,000, 6,000 or 8,000 mg. Low levels of curcumin were detected in two subjects administered 10,000 or 12,000 mg.ConclusionThe tolerance of curcumin in high single oral doses appears to be excellent. Given that achieving systemic bioavailability of curcumin or its metabolites may not be essential for colorectal cancer chemoprevention, these findings warrant further investigation for its utility as a long-term chemopreventive agent.

Recent studies have suggested that the gut microbiome may be an important factor in the development of colorectal cancer (CRC). Abnormalities in the gut microbiome have been reported in patients with CRC; however, this microbial community has not been explored as a potential screen for early stage disease. We characterized the gut microbiome in patients from three clinical groups representing the stages of CRC development: health, adenoma, and carcinoma. Analysis of the gut microbiome from stool samples revealed both an enrichment and depletion of several bacterial populations associated with adenomas and carcinomas. Combined with known clinical risk factors of CRC (e.g. BMI, age, race), data from the gut microbiome significantly improved the ability to differentiate between healthy, adenoma, and carcinoma clinical groups relative to risk factors alone. Using Bayesian methods, we determined that using gut microbiome data as a screening tool improved the pre-test to post-test probability of adenoma over 50-fold. For example, the pre-test probability in a 65 year-old was 0.17% and, after using the microbiome data, this increased to 10.67% (1 in 9 chance of having an adenoma). Taken together the results of our study demonstrate the feasibility of using the composition of the gut microbiome to detect the presence of precancerous and cancerous lesions. Furthermore, these results support the need for more cross sectional studies with diverse populations and linkage to other stool markers, dietary data, and personal health information.

BackgroundColorectal cancer (CRC) is the second leading cause of death among cancers in the United States. Although individuals diagnosed early have a greater than 90 % chance of survival, more than one-third of individuals do not adhere to screening recommendations partly because the standard diagnostics, colonoscopy and sigmoidoscopy, are expensive and invasive. Thus, there is a great need to improve the sensitivity of non-invasive tests to detect early stage cancers and adenomas. Numerous studies have identified shifts in the composition of the gut microbiota associated with the progression of CRC, suggesting that the gut microbiota may represent a reservoir of biomarkers that would complement existing non-invasive methods such as the widely used fecal immunochemical test (FIT).MethodsWe sequenced the 16S rRNA genes from the stool samples of 490 patients. We used the relative abundances of the bacterial populations within each sample to develop a random forest classification model that detects colonic lesions using the relative abundance of gut microbiota and the concentration of hemoglobin in stool.ResultsThe microbiota-based random forest model detected 91.7 % of cancers and 45.5 % of adenomas while FIT alone detected 75.0 % and 15.7 %, respectively. Of the colonic lesions missed by FIT, the model detected 70.0 % of cancers and 37.7 % of adenomas. We confirmed known associations of Porphyromonas assaccharolytica, Peptostreptococcus stomatis, Parvimonas micra, and Fusobacterium nucleatum with CRC. Yet, we found that the loss of potentially beneficial organisms, such as members of the Lachnospiraceae, was more predictive for identifying patients with adenomas when used in combination with FIT.ConclusionsThese findings demonstrate the potential for microbiota analysis to complement existing screening methods to improve detection of colonic lesions.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-016-0290-3) contains supplementary material, which is available to authorized users.

Background: Curcumin is a polyphenol, found in the spice turmeric, that has promising anticancer properties, but previous studies suggest that absorption of curcumin may be limited. Methods: This study examined the pharmacokinetics of a curcumin preparation in healthy human volunteers 0.25 to 72 h after a single oral dose. Curcumin was administered at doses of 10 g (n = 6) and 12 g (n = 6). Subjects were randomly allocated to dose level for a total of six subjects at each dose level. Serum samples were assayed for free curcumin, for its glucuronide, and for its sulfate conjugate. The data were fit to a onecompartment absorption and elimination model. Results: Using a high-performance liquid chromatography assay with a limit of detection of 50 ng/mL, only

Background: Ginger shows promising anticancer properties. No research has examined the pharmacokinetics of the ginger constituents 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol in humans. We conducted a clinical trial with 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol, examining the pharmacokinetics and tolerability of these analytes and their conjugate metabolites. Methods: Human volunteers were given ginger at doses from 100 mg to 2.0 g (N = 27), and blood samples were obtained at 15 minutes to 72 hours after a single p.o. dose. The participants were allocated in a doseescalation manner starting with 100 mg. There was a total of three participants at each dose except for 1.0 g (N = 6) and 2.0 g (N = 9). Results: No participant had detectable free 6-gingerol, 8-gingerol, 10-gingerol, or 6-shogaol, but 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol glucuronides were detected. The 6-gingerol sulfate conjugate was

PURPOSE The objective of this study was to compare the reasons why mothers do or do not have their adolescent daughters vaccinated against HPV. METHODS Mothers of vaccinated and unvaccinated 11- to 17-year-old girls seen during preventive care visits in outpatient family medicine or pediatric clinics underwent an audiotaped structured telephone interview that used open-ended questions to assess the reasons underlying maternal decisions about HPV vaccination. Qualitative methods categorized maternal responses into themes. RESULTS Interviews of 52 mothers (19 declining vaccination, 33 accepting) identified several distinct factors underlying their decisions about HPV vaccination. Lack of knowledge about HPV, age-related concerns, and low perceived risk of infection were commonly cited reasons for declining vaccination. Desire to prevent illness, physician recommendation, and a high perceived risk of infection were commonly identified motivating factors. Both groups of mothers had significant concerns about vaccine safety. Locus of control (e.g., mother or daughter) of health-related decisions arose as a novel factor influencing this decision that had not been previously described in the context of HPV vaccination. CONCLUSIONS Addressing safety concerns, educating parents about the age-specific risk of HPV infection, and promoting strong physician recommendation for vaccination may be the most useful targets for future interventions to increase HPV vaccine utilization.

Colorectal cancer is a leading cause of cancer-related death in the United States and worldwide. Its risk and severity have been linked to colonic bacterial community composition. Although human-specific viruses have been linked to other cancers and diseases, little is known about colorectal cancer virus communities. We addressed this knowledge gap by identifying differences in colonic virus communities in the stool of colorectal cancer patients and how they compared to bacterial community differences. The results suggested an indirect role for the virome in impacting colorectal cancer by modulating the associated bacterial community. These findings both support the idea of a biological role for viruses in colorectal cancer and provide a new understanding of basic colorectal cancer etiology.

What environmental factors stimulate and maintain research productivity? To answer this question, the authors conducted an extensive review of articles and books on research productivity published from the mid-1960s through 1990. This review revealed that a consistent set of 12 characteristics was found in research-conducive environments: (1) clear goals that serve a coordinating function, (2) research emphasis, (3) distinctive culture, (4) positive group climate, (5) assertive participative governance, (6) decentralized organization, (7) frequent communication, (8) accessible resources, particularly human, (9) sufficient size, age, and diversity of the research group, (10) appropriate rewards, (11) concentration on recruitment and selection, and (12) leadership with research expertise and skill in both initiating appropriate organizational structure and using participatory management practices. Some of these characteristics are not surprising, although some findings were unexpected, such as that participative governance correlated consistently with research productivity. The differential impact of each of these 12 characteristics is unclear. It is clear, however, that the leader has a disproportionate impact through his or her influence on all of the other characteristics. Yet, an overarching feature of these characteristics is their interdependency. These factors do not operate in research groups as isolated characteristics. Rather, they are like fine threads of a whole fabric: individual, yet when interwoven, providing a strong, supportive, and stimulating backdrop for the researcher. The authors conclude that while at a distance the productive research enterprise looks like a highly robust entity, upon closer inspection it is revealed to be a delicate structure highly dependent on the existence and effective working of numerous individual, organizational, and leadership characteristics.