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Richard Mithen

Bio: Richard Mithen is an academic researcher from Norwich Research Park. The author has contributed to research in topics: Glucosinolate & Sulforaphane. The author has an hindex of 41, co-authored 125 publications receiving 8966 citations. Previous affiliations of Richard Mithen include University of Nottingham & University of Auckland.


Papers
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TL;DR: There are multiple mechanisms activated in response to SF, including suppression of cytochrome P450 enzymes, induction of apoptotic pathways, suppression of cell cycle progression, inhibition of angiogenesis and anti-inflammatory activity, and these mechanisms seem to have some degree of interaction to synergistically afford chemoprevention.
Abstract: The consumption of cruciferous vegetables has long been associated with a reduced risk in the occurrence of cancer at various sites, including the prostate, lung, breast and colon. This protective effect is attributed to isothiocyanates present in these vegetables, and sulforaphane (SF), present in broccoli, is by far the most extensively studied to uncover the mechanisms behind this chemoprotection. The major mechanism by which SF protects cells was traditionally thought to be through Nrf2-mediated induction of phase 2 detoxification enzymes that elevate cell defense against oxidative damage and promote the removal of carcinogens. However, it is becoming clear that there are multiple mechanisms activated in response to SF, including suppression of cytochrome P450 enzymes, induction of apoptotic pathways, suppression of cell cycle progression, inhibition of angiogenesis and anti-inflammatory activity. Moreover, these mechanisms seem to have some degree of interaction to synergistically afford chemoprevention.

672 citations

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TL;DR: The effects of various factors in the supply chain of Brassica vegetables including breeding, cultivation, storage and processing on intake and bioavailability of GLSs are extensively discussed in this article.
Abstract: Glucosinolates (GLSs) are found in Brassica vegetables. Examples of these sources include cabbage, Brussels sprouts, broccoli, cauliflower and various root vegetables (e.g. radish and turnip). A number of epidemiological studies have identified an inverse association between consumption of these vegetables and the risk of colon and rectal cancer. Animal studies have shown changes in enzyme activities and DNA damage resulting from consumption of Brassica vegetables or isothiocyanates, the breakdown products (BDP) of GLSs in the body. Mechanistic studies have begun to identify the ways in which the compounds may exert their protective action but the relevance of these studies to protective effects in the human alimentary tract is as yet unproven. In vitro studies with a number of specific isothiocyanates have suggested mechanisms that might be the basis of their chemoprotective effects. The concentration and composition of the GLSs in different plants, but also within a plant (e.g. in the seeds, roots or leaves), can vary greatly and also changes during plant development. Furthermore, the effects of various factors in the supply chain of Brassica vegetables including breeding, cultivation, storage and processing on intake and bioavailability of GLSs are extensively discussed in this paper.

531 citations

Journal ArticleDOI
TL;DR: An overview of the evidence for a beneficial role for glucosinolates in human health is provided, and the current state of knowledge regarding the genetics and biosynthesis of glucos inolates, their chemical analysis, their behaviour during cooking and processing, and their bioavailability to humans are described.
Abstract: The glucosinolates are a large group of sulphur-containing compounds which occur in all the economically important varieties of Brassica vegetable. Their common structure comprises a β-D-thioglucose group, a sulphonated oxime moiety and a variable side-chain derived from methionine, tryptophan or phenylalanine. When the plant tissue is damaged the glucosinolates are hydrolysed by the endogenous enzyme ‘myrosinase’ (thioglucoside glycohydrolase EC 3:2:3:1), to release a range of breakdown products including the bitter, biologically active isothiocyanates. Although these compounds exert antinutritional effects in animals there is also substantial evidence that they are the principal source of anticarcinogenic activity in Brassica vegetables, and this provides a strong motive for the manipulation of glucosinolate levels in vegetables for human consumption. This review provides an overview of the evidence for a beneficial role for glucosinolates in human health, and describes the current state of knowledge regarding the genetics and biosynthesis of glucosinolates, their chemical analysis, their behaviour during cooking and processing, and their bioavailability to humans. As the genetic basis of glucosinolate biosynthesis becomes more apparent, and tools for marker-assisted plant breeding become more available, the selective breeding of horticultural brassicas with different levels and types of glucosinolates, whether by conventional means or genetic manipulation, is becoming a practical possibility. However before this strategy becomes commercially viable, the health benefits of glucosinolates for human beings must be unequivocally established. © 2000 Society of Chemical Industry

445 citations

Journal ArticleDOI
TL;DR: The epidemiological evidence for the health promoting effects of cruciferous vegetables, the processes by which glucosinolates and isothiocyanates are absorbed and metabolised by humans, and the role of glutathione S-transferases are reviewed are reviewed.
Abstract: Concurrent with the increase in our knowledge of the genetic and environmental factors that lead to glucosinolate accumulation in plants, and the role of these compounds and their derivatives in mediating plant–herbivore interactions, there has been significant advances in our understanding of how glucosinolates and their products may contribute to a reduction in risk of carcinogenesis and heart disease when consumed as part of the diet. In this paper, we review the epidemiological evidence for the health promoting effects of cruciferous vegetables, the processes by which glucosinolates and isothiocyanates are absorbed and metabolised by humans, with particular regard to the role of glutathione S-transferases, and the biological activity of isothiocyanates towards mammalian cells and tissues.

427 citations

Journal ArticleDOI
TL;DR: Genome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men, demonstrating the existence of ongoing abnormal mutational processes, consistent with field effects, underlying carcinogenesis.
Abstract: Genome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer, reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of ongoing abnormal mutational processes, consistent with field effects, underlying carcinogenesis. This mechanism gives rise to extensive branching evolution and cancer clone mixing, as exemplified by the coexistence of multiple cancer lineages harboring distinct ERG fusions within a single cancer nodule. Subsets of mutations were shared either by morphologically normal and malignant tissues or between different ERG lineages, indicating earlier or separate clonal cell expansions. Our observations inform on the origin of multifocal disease and have implications for prostate cancer therapy in individual cases.

396 citations


Cited by
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Journal ArticleDOI
Dan R. Robinson1, Eliezer M. Van Allen2, Eliezer M. Van Allen3, Yi-Mi Wu1, Nikolaus Schultz4, Robert J. Lonigro1, Juan Miguel Mosquera, Bruce Montgomery5, Mary-Ellen Taplin3, Colin C. Pritchard5, Gerhardt Attard6, Gerhardt Attard7, Himisha Beltran, Wassim Abida4, Robert K. Bradley5, Jake Vinson4, Xuhong Cao1, Pankaj Vats1, Lakshmi P. Kunju1, Maha Hussain1, Felix Y. Feng1, Scott A. Tomlins, Kathleen A. Cooney1, David Smith1, Christine Brennan1, Javed Siddiqui1, Rohit Mehra1, Yu Chen8, Yu Chen4, Dana E. Rathkopf4, Dana E. Rathkopf8, Michael J. Morris8, Michael J. Morris4, Stephen B. Solomon4, Jeremy C. Durack4, Victor E. Reuter4, Anuradha Gopalan4, Jianjiong Gao4, Massimo Loda, Rosina T. Lis3, Michaela Bowden9, Michaela Bowden3, Stephen P. Balk10, Glenn C. Gaviola9, Carrie Sougnez2, Manaswi Gupta2, Evan Y. Yu5, Elahe A. Mostaghel5, Heather H. Cheng5, Hyojeong Mulcahy5, Lawrence D. True11, Stephen R. Plymate5, Heidi Dvinge5, Roberta Ferraldeschi6, Roberta Ferraldeschi7, Penny Flohr6, Penny Flohr7, Susana Miranda6, Susana Miranda7, Zafeiris Zafeiriou7, Zafeiris Zafeiriou6, Nina Tunariu7, Nina Tunariu6, Joaquin Mateo7, Joaquin Mateo6, Raquel Perez-Lopez7, Raquel Perez-Lopez6, Francesca Demichelis12, Francesca Demichelis8, Brian D. Robinson, Marc H. Schiffman8, David M. Nanus, Scott T. Tagawa, Alexandros Sigaras8, Kenneth Eng8, Olivier Elemento8, Andrea Sboner8, Elisabeth I. Heath13, Howard I. Scher4, Howard I. Scher8, Kenneth J. Pienta14, Philip W. Kantoff3, Johann S. de Bono7, Johann S. de Bono6, Mark A. Rubin, Peter S. Nelson, Levi A. Garraway3, Levi A. Garraway2, Charles L. Sawyers4, Arul M. Chinnaiyan 
21 May 2015-Cell
TL;DR: This cohort study provides clinically actionable information that could impact treatment decisions for affected individuals and identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF.

2,713 citations

Journal ArticleDOI
TL;DR: This review addresses the complex array of glucosinolates, the precursors of isothiocyanates, present in sixteen families of dicotyledonous angiosperms including a large number of edible species including Brassica vegetables.

2,679 citations

Journal ArticleDOI
Adam Abeshouse1, Jaeil Ahn1, Rehan Akbani1, Adrian Ally1  +308 moreInstitutions (1)
05 Nov 2015-Cell
TL;DR: The Cancer Genome Atlas (TCGA) has been used for a comprehensive molecular analysis of primary prostate carcinomas as discussed by the authors, revealing substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course.

2,109 citations

Journal ArticleDOI
TL;DR: Glucosinolates are sulfur-rich, anionic natural products that upon hydrolysis by endogenous thioglucosidases called myrosinases produce several different products that function as cancer-preventing agents, biopesticides, and flavor compounds.
Abstract: Glucosinolates are sulfur-rich, anionic natural products that upon hydrolysis by endogenous thioglucosidases called myrosinases produce several different products (e.g., isothiocyanates, thiocyanates, and nitriles). The hydrolysis products have many different biological activities, e.g., as defense compounds and attractants. For humans these compounds function as cancer-preventing agents, biopesticides, and flavor compounds. Since the completion of the Arabidopsis genome, glucosinolate research has made significant progress, resulting in near-complete elucidation of the core biosynthetic pathway, identification of the first regulators of the pathway, metabolic engineering of specific glucosinolate profiles to study function, as well as identification of evolutionary links to related pathways. Although much has been learned in recent years, much more awaits discovery before we fully understand how and why plants synthesize glucosinolates. This may enable us to more fully exploit the potential of these compounds in agriculture and medicine.

1,955 citations

Journal ArticleDOI
TL;DR: Evidence that inflammation is the link between the agents/factors that cause cancer and the agents that prevent it is presented and evidence that cancer is a preventable disease that requires major lifestyle changes is provided.
Abstract: This year, more than 1 million Americans and more than 10 million people worldwide are expected to be diagnosed with cancer, a disease commonly believed to be preventable. Only 5–10% of all cancer cases can be attributed to genetic defects, whereas the remaining 90–95% have their roots in the environment and lifestyle. The lifestyle factors include cigarette smoking, diet (fried foods, red meat), alcohol, sun exposure, environmental pollutants, infections, stress, obesity, and physical inactivity. The evidence indicates that of all cancer-related deaths, almost 25–30% are due to tobacco, as many as 30–35% are linked to diet, about 15–20% are due to infections, and the remaining percentage are due to other factors like radiation, stress, physical activity, environmental pollutants etc. Therefore, cancer prevention requires smoking cessation, increased ingestion of fruits and vegetables, moderate use of alcohol, caloric restriction, exercise, avoidance of direct exposure to sunlight, minimal meat consumption, use of whole grains, use of vaccinations, and regular check-ups. In this review, we present evidence that inflammation is the link between the agents/factors that cause cancer and the agents that prevent it. In addition, we provide evidence that cancer is a preventable disease that requires major lifestyle changes.

1,915 citations