Old Problems and New Challenges Chemoprevention Of Colorectal Cancer

( James A. Disario ) 대한소화기학회 2007 SIDDS Vol.9 No.-

Chemoprevention of cancer entails using medications to inhibit the development of this disease. Nonsteroidal anti-inflammatory drugs are the best studied and appear to be effective with about a 40 percent decrease in cancer incidence and possibly deaths. Additional potentially effective agents include calcium, folic acid, estrogen and progesestins, statins, ursodeoxycholic acid, selenium, thiazolidines (gilatzones), and others. Risk stratification based on familial occurrence and potentially environmental factors is key to determining persons who may receive the most benefit from therapy. However, chemoprevention does not appear to be cost effective except in persons with the highest risk inherited syndromes. At present, the United States Preventative Services Task Force and the American Cancer Society do not recommend routine chemoprevention.

The Promise of Dried Fruits in Cancer Chemoprevention

Kundu, Joydeb Kumar,Chun, Kyung-Soo Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.8

Chemoprevention is an attempt to use nontoxic natural and synthetic substances or their mixtures to intervene the relatively early stages of carcinogenesis, before invasive characteristics are manifested. The consumption of fruits is well known to reduce the risk of human cancers. Although most fruits are available only on a seasonal basis, recent advances in food processing technologies have made it possible to extend the shelf life of fruits and fruit-products. Fruits can be preserved by applying different drying processes to reduce the moisture content. Different varieties of dried fruits are now sold in supermarkets, thereby making them readily accessible to consumers. Since oxidative stress and chronic inflammation play important roles in cancer development, dried fruits with antioxidative and anti-inflammatory properties hold promise for cancer chemoprevention. The antioxidant, anti-inflammatory and chemopreventive activities of dried fruits are largely attributed to their polyphenols and vitamins. Dried fruits contain adequate amounts of bioactive principles, such as anthocyanins, acetogenins, catechins, coumarins, phenolic acids, terpenes, xanthones, and others. Since numerous health beneficial phytochemicals in fruits are conserved even after processing, regular intake of dried fruits can help prevent cancer. This review addresses the chemopreventive potential of representative dried fruits and their active constituents.

Signal Transduction Network Leading to COX-2 Induction: A Road Map in Search of Cancer Chemopreventives

Surh Young-Joon,Kundu Joydeb Kumar The Pharmaceutical Society of Korea 2005 Archives of Pharmacal Research Vol.28 No.1

Cancer is still a major global health concern even after an everlasting strive in conquering this dread disease. Emphasis is now given to chemoprevention to reduce the risk of cancer and also to improve the quality of life among cancer afflicted individuals. Recent progress in molecular biology of cancer has identified key components of the cellular signaling network, whose functional abnormality results in undesired alterations in cellular homeostasis, creating a cellular microenvironment that favors premalignant and malignant transformation. Multiple lines of evidence suggest an elevated expression of cyclooxygenase-2 (COX-2) is causally linked to cancer. In response to oxidative/pro-inflammatory stimuli, turning on unusual signaling arrays mediated through diverse classes of kinases and transcription factors results in aberrant expression of COX-2. Population-based as well as laboratory studies have explored a broad spectrum of chemopreventive agents including selective COX-2 inhibitors and a wide variety of anti-inflammatory phytochemicals, which have been shown to target cellular signaling molecules as underlying mechanisms of chemoprevention. Thus, unraveling signaling pathways regulating aberrant COX-2 expression and targeted blocking of one or more components of those signal cascades may be exploited in searching chemopreventive agents in the future.

siTRP (short-term intervention To Revert Premalignancy) as strategy to prevent GI malignancy

한영민,함기백,이호재,박정민,김은희 대한암예방학회 2013 Journal of cancer prevention Vol.18 No.4

“Prevention might be better than treatment in cancer treatment” is brief conclusion drawn from war on cancer through National Cancer Act of 1971 by U.S. President Richard Nixon. However, the clinical practice of chemoprevention is still in its infancy in spite of a wealth of data showing its effectiveness in experimental animals as well as in vitro mechanism research. Recent advances in either high throughput analysis including cancer genomes and tailored medicine or molecular targeted therapeutics, preventive strategies also should be changes as previous preventive strategies including phytoceuticals, life-style modification, and some empirical agents. Furthermore, molecular targeted therapeutics achieved high goal of effectiveness under the concept of therapeutic or preventive “synthetic lethality”, of which extended application can be included within the scope of chemoprevention. Here, we will summarize several recent advances in chemopreventive strategy objected to justify optimism that chemoprevention will be an effective approach for the control of human cancer. siTRP (short-term intervention to revert premalignancy) strategy will be introduced for cancers in gastroenterology.

Breaking the relay in deregulated cellular signal transduction as a rationale for chemoprevention with anti-inflammatory phytochemicals

Kundu, Joydeb Kumar,Surh, Young-Joon Elsevier 2005 Mutation research Vol.591 No.1-2

<P><B>Abstract</B></P><P>Center to the cancer biology is disrupted intracellular signaling network, which transmits improper signals resulting in abnormal cellular functioning. Therefore, modulation of inappropriate cell signaling cascades might be a rational approach in achieving chemoprevention. Inflammation has long been suspected to contribute to carcinogenesis. A new horizon in chemoprevention research is the recent discovery of molecular links between inflammation and cancer. Components of the cell signaling network, especially those converge on redox-sensitive transcription factor nuclear factor-κB involved in mediating inflammatory response, have been implicated in carcinogenesis. Intracellular signaling through another redox-sensitive transcription factor AP-1 and that transmitted via a more recently identified oncoprotein β-catenin are also considered to be crucial for inflammation-associated cancer. Epidemiological and experimental studies have revealed that a wide variety of phytochemicals present in our daily diet are potential chemopreventive agents that can alter or correct undesired cellular functions caused by abnormal pro-inflammatory signal transmission. Modulation of cellular signaling involved in chronic inflammatory response by anti-inflammatory phytochemicals may comprise a rational and pragmatic strategy in molecular target-based chemoprevention.</P>

Cancer Chemopreventive Effects of Korean Seaweed Extracts

Saet Byoul Lee,Joo Young Lee,Dae-Geun Song,Cheol-Ho Pan,Chu Won Nho,Min Cheol Kim,Eun Ha Lee,Sang Hoon Jung,Hyung-Seop Kim,Yeong Shik Kim,Byung Hun Um 한국식품과학회 2008 Food Science and Biotechnology Vol.17 No.3

Cancer chemopreventive effects can be exerted through the induction of phase II detoxification enzymes and the inhibition of inflammatory responses. In this study, the cancer chemopreventive effects and anti-inflammatory responses of 30 seaweed extracts were examined. The extracts of Dictyota coriacea and Cutleria cylindrica exhibited the high chemoprevention index, having 4.36 and 4.66, respectively. They also activated antioxidant response element at 100 μg/mL by about 3-fold while did not activate xenobiotic response element. Seven seaweed extracts, Ishige okamurae, Desmarestia ligulata, Desmarestia viridis, Dictyopteris divaricata, D. coriacea, Sargassum horneri, and Sargassum yezoense, showed significant inhibition on nitric oxide (NO) and prostaglandin E₂ (PGE₂) production in a dose-dependant manner in 5-20 μg/mL. These seaweed extracts could be used as food materials for cancer chemoprevention. D. coriacea could contain potential chemopreventive agents not only that regulate genes via an ARE-dependent mechanism but also prevent the inflammation through inhibition of NO and PGE₂ production.

The Chemopreventive Effect of Taxifolin Is Exerted through ARE-Dependent Gene Regulation

Lee, Saet Byoul,Cha, Kwang Hyun,Selenge, Dangaa,Solongo, Amgalan,Nho, Chu Won Pharmaceutical Society of Japan 2007 Biological & pharmaceutical bulletin Vol.30 No.6

<P>Phase II detoxification enzymes are responsible for the detoxification and elimination of activated carcinogens, and thus act as important biomarkers for chemoprevention. In this study, we tested the chemopreventive activity of taxifolin, a flavanon compound purified from a mongolian medicinal plant, by measuring quinone reductase (QR) activity in HCT 116 cells. Taxifolin induced significant QR activity, but displayed relatively low cytotoxicity in cells (chemoprevention index=5.75). To identify the target genes regulated by taxifolin, DNA microarray was performed with a 3K human cancer chip containing 3096 human genes associated with carcinogenesis. Significant analysis of microarray (SAM) revealed 428 differentially expressed (DE) genes as statistically significant, with a false discovery rate (FDR) of 57.2% (delta=0.3366). Sixty-five genes, including a few detoxification enzymes (<I>NQO1</I>, <I>GSTM1</I>) and an antioxidant enzyme (<I>TXNRD1</I>), were up-regulated and 363 genes were down-regulated in the presence of 60 μ<SMALL>M</SMALL> taxifolin. In view of the finding that selected genes of interest contained antioxidant response element (ARE), we hypothesize that taxifolin modulates chemopreventive genes through activation of the ARE. Transient transfection experiments using the ARE QR-CAT construct demonstrate that taxifolin significantly activates ARE, but not xenobiotic response element (XRE). In conclusion, taxifolin acts as a potential chemopreventive agent by regulating genes <I>via</I> an ARE-dependent mechanism.</P>

Cancer Chemoprevention by Dietary Proanthocyanidins

Jeong-Youn Jo,Chang Yong Lee 한국식품과학회 2007 Food Science and Biotechnology Vol.16 No.4

Proanthocyanidins (PACs), also named condensed tannins, are polymers of flavan-3-ols such as (+)-(gallo)catechin and (-)-epi(gallo)catechin. A proper analysis of the PACs, with difficult challenges due to their complex structures, is crucial in studies of cancer chemoprevention. Cancer is a leading cause of mortality around the world. Many experimental studies have shown that dietary PACs are potential chemopreventive agents that block or suppress against multistage carcinogenesis in both in vitro and in vivo models. Cancer chemoprevention by dietary PACs has been shown effective through different mechanisms of action such as antioxidant, apoptosis-inducing, and enzyme inhibitory activities. Good sources of dietary PACs are nuts, fruits, beans, chocolate, fruit juice, red wine, and green tea. The chemopreventive potential of dietary PACs should be considered together with their bioavailability in humans. The safety issues regarding carcinogenesis and gastrointestinal disorder are also reviewed.

Estimating the Risks and Benefits of Tamoxifen for Prophylactic Breast Cancer Chemoprevention in Korea

김동욱,민준원,김유미,장명철 한국유방암학회 2012 Journal of breast cancer Vol.15 No.1

Purpose: According to the National Surgical Adjuvant Breast and Bowel Project P1 (NSABP-P1) study, tamoxifen can prevent 49% of invasive breast cancers in patients who have a 5-year risk of 1.67% or more. Because tamoxifen is associated with both adverse effects (endometrial cancer, stroke, pulmonary embolism) and protective effect (fracture prevention), it is necessary to weigh the risks and benefits of using tamoxifen for prevention in Korean women. This study weighed those risks and benefits. Methods: Data were reviewed on the incidences of breast cancer, hip fracture, endometrial cancer and stroke in the absence of tamoxifen treatment in Korean women. We also reviewed NSABP-P1 data on the effects of tamoxifen on these outcomes. A risk-benefit index was calculated according to age and specific risk of breast cancer. Sensitivity analyses were performed with assumptions regarding the effects of tamoxifen. Results: Compared to U.S. women, the numbers of hip fractures and endometrial cancers were lower, but the number of strokes was much higher. The net benefit of tamoxifen was reduced with increasing age because of a high risk of stroke in older women. Older Korean women had more risk than benefit from tamoxifen chemoprevention. Only women younger than age 40 had a positive riskbenefit index with an average 5-year risk of breast cancer in Korea. Sensitivity analysis showed that this result was robust. Conclusion: Women under the age 40 had more benefit than risk from tamoxifen chemoprevention. Tamoxifen chemoprevention should be limited to Korean women younger than age 40.

바렛식도의 화학예방

송경호 대한소화기암연구학회 2023 Journal of Digestive Cancer Research (JDCR) Vol.11 No.1

The prevalence of Barrett’s esophagus is increasing in South Korea. Several strategies have been tried to prevent its progression to esophageal adenocarcinoma. It is questionable whether the strategies being tried in the West can be applied adequately in South Korea. However, despite the incidence of esophageal adenocarcinoma in the West, which is considerably higher than that in South Korea, the incidence of high-grade dysplasia/esophageal adenocarcinoma in population-based studies is as low as 0.23%/person-year. Therefore, in Korea, where the prevalence is lower than that, it is necessary to select high-risk groups more carefully for chemoprevention. The age of onset of gastroesophageal reflux disease-like symptoms at least once a week is related to the high-risk group rather than the presence or absence of chronic gastroesophageal reflux symptoms. The risk factors for esophageal adenocarcinoma include the patient’s sex, age, smoking habit, and obesity. Proton pump inhibitors have a better preventive effect against esophageal adenocarcinoma compared to H2-receptor blockers, but their application to patients in Korea is limited due to the high number of individuals in need of treatment. Therefore, while considering the risk factors for the progression of esophageal adenocarcinoma, the administration of proton pump inhibitors should be considered for gastroesophageal reflux disease.