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Characterizing the efficacy of fermented wheat germ extract against ovarian cancer and defining the genomic basis of its activity.

ABSTRACT: OBJECTIVE:Most women with advanced-stage epithelial ovarian cancer (OVCA) ultimately develop chemoresistant recurrent disease. Therefore, a great need to develop new, more active, and less toxic agents and/or to optimize the efficacy of existing agents exists. METHODS:In this study, we investigated the activity of Avemar, a natural, nontoxic, fermented wheat germ extract (FWGE), against a range of OVCA cell lines, both alone and in combination with cisplatin chemotherapy and delineated the molecular signaling pathways that underlie FWGE activity at a genome-wide level. RESULTS:We found that FWGE exhibited significant antiproliferative effects against 12 human OVCA cell lines and potentiated cisplatin-induced apoptosis. Pearson correlation of FWGE sensitivity and gene expression data identified 2142 genes (false discovery rate < 0.2) representing 27 biologic pathways (P < 0.05) to be significantly associated with FWGE sensitivity. A parallel analysis of genomic data for 59 human cancer cell lines matched to chemosensitivity data for 2,6-dimethoxy-p-benzoquinone, a proposed active component of FWGE, identified representation of 13 pathways common to both FWGE and 2,6-dimethoxy-p-benzoquinone sensitivity. CONCLUSIONS:Our findings confirm the value of FWGE as a natural product with anticancer properties that may also enhance the activity of existing therapeutic agents. Furthermore, our findings provide substantial insights into the molecular basis of FWGE's effect on human cancer cells.

SUBMITTER: Judson PL

PROVIDER: S-EPMC4036555 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Characterizing the efficacy of fermented wheat germ extract against ovarian cancer and defining the genomic basis of its activity.

Judson Patricia L PL Al Sawah Entidhar E Marchion Douglas C DC Xiong Yin Y Bicaku Elona E Bou Zgheib Nadim N Chon Hye Sook HS Stickles Xiaomang B XB Hakam Ardeshir A Wenham Robert M RM Apte Sachin M SM Gonzalez-Bosquet Jesus J Chen Dung-Tsa DT Lancaster Johnathan M JM

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 20120701 6

<h4>Objective</h4>Most women with advanced-stage epithelial ovarian cancer (OVCA) ultimately develop chemoresistant recurrent disease. Therefore, a great need to develop new, more active, and less toxic agents and/or to optimize the efficacy of existing agents exists.<h4>Methods</h4>In this study, we investigated the activity of Avemar, a natural, nontoxic, fermented wheat germ extract (FWGE), against a range of OVCA cell lines, both alone and in combination with cisplatin chemotherapy and delin ...[more]

PMID: 22740002

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Project description:BackgroundTask shifting could help address limited human resources available for the delivery of quality health care services in low-resource settings. However, the role of medical devices in supporting task shifting is not fully understood. This study aimed to 1) define "task-shifting medical devices" and 2) identify product characteristics to guide the design and development of task-shifting medical devices. A three-part survey questionnaire comprising open-ended, rank-ordering, and multiple-choice questions was disseminated to healthcare professionals worldwide. The survey included questions to capture stakeholders' general understanding of and preferences for task shifting in medicine and public health, and questions to define task-shifting medical devices and identify desirable product characteristics of task-shifting medical devices.ResultsTask-shifting medical devices were defined by respondents as "devices that can be used by a less specialized health worker". Aside from safe and effective, both essential characteristics for medical devices, easy to use was the most cited product characteristic for a task-shifting medical device. Responses also emphasized the importance of task-shifting medical devices to enable local agency, such as peer-to-peer training and local maintenance. Several additional frequently mentioned attributes included low cost, contextually appropriate, maintainable, capable of using an alternative power source, easy to understand, easy to learn, reusable, and easy to manage throughout its use cycle.ConclusionThis study defines and characterizes task-shifting medical devices based on healthcare professionals' responses. Ease of use was identified as the most important characteristic that defines a task-shifting medical device, alongside safe and effective, and was strongly associated with enabling peer-to-peer training and maintainability. The findings from this study can be used to inform technology product profiles for medical devices used by lower-level cadres of healthcare workers in low-resource settings.

Project description:BackgroundGenetic variation in growth over the course of the season is a major source of grain yield variation in wheat, and for this reason variants controlling heading date and plant height are among the best-characterized in wheat genetics. While the major variants for these traits have been cloned, the importance of these variants in contributing to genetic variation for plant growth over time is not fully understood. Here we develop a biparental population segregating for major variants for both plant height and flowering time to characterize the genetic architecture of the traits and identify additional novel QTL.ResultsWe find that additive genetic variation for both traits is almost entirely associated with major and moderate-effect QTL, including four novel heading date QTL and four novel plant height QTL. FT2 and Vrn-A3 are proposed as candidate genes underlying QTL on chromosomes 3A and 7A, while Rht8 is mapped to chromosome 2D. These mapped QTL also underlie genetic variation in a longitudinal analysis of plant growth over time. The oligogenic architecture of these traits is further demonstrated by the superior trait prediction accuracy of QTL-based prediction models compared to polygenic genomic selection models.ConclusionsIn a population constructed from two modern wheat cultivars adapted to the southeast U.S., almost all additive genetic variation in plant growth traits is associated with known major variants or novel moderate-effect QTL. Major transgressive segregation was observed in this population despite the similar plant height and heading date characters of the parental lines. This segregation is being driven primarily by a small number of mapped QTL, instead of by many small-effect, undetected QTL. As most breeding populations in the southeast U.S. segregate for known QTL for these traits, genetic variation in plant height and heading date in these populations likely emerges from similar combinations of major and moderate effect QTL. We can make more accurate and cost-effective prediction models by targeted genotyping of key SNPs.

Dataset Information

Characterizing the efficacy of fermented wheat germ extract against ovarian cancer and defining the genomic basis of its activity.

Publications

Characterizing the efficacy of fermented wheat germ extract against ovarian cancer and defining the genomic basis of its activity.

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