A free radical is any chemical species (capable of independent existence) possessing one or more unpaired electrons, an unpaired electron being one that is alone in an orbital. Radicals (often denoted by the insertion of the radical dot (ㆍ) to indicate that one or more unpaired electrons is present) are generally less stable than non-radicals, although their reactivities vary.

Several micronutrients (vitamins and minerals) are required as co-factors in DNA synthesis, DNA repair, DNA methylation and apoptosis. Some notable examples include (a) folic acid and vitamin B12 required for maintenance methylation of DNA and the synthesis of dTTP from dUTP, thus prevent the misincorporation of uracil into DNA, a highly mutagenic and chromosome-breaking event, (b) niacin, is essential in the form of the coenzymes NAD and NADP which act as a substrate for polyADPribose polymerase (PARP), an enzyme thought to facilitate efficient DNA repair and telomere length regulation and (c) zinc, apart from its antioxidant role as a co-factor in Cu/Zn SOD, it is required in its stabilizing role of the DNA-binding domain of p53 (residues 102-292) and thus is essential for apoptotic response to DNA damage. (omitted)

Selenium is an essential nutritional element for several animal species and human. It has been also seen, that low levels of selenium in the diet can cause many diseases. This metalloid was defined like a "double face" element because it possesses antioxidant, antimutagen, anticarcinogen but also mutagenic and carcinogenic effects. The most important metabolic role of selenium in the animal species is its presence in the Glutathione Peroxidase(GSH-Px). (omitted)

Selenium is known to have both chemopreventive and therapeutic benefits of cancer. Recent studies have implicated that apoptosis is one of the most plausible mechanism of chemopreventive effects of selenium compounds and tumor invasion is a new factor involved in chemotherapy. In the present study, we demonstrate that Se-methylselenocysteine(MSC), one of the most effective selenium compound sat chemoprevention, induces apoptosis in HL-60 cells and that ROS plays a crucial role in MSC-induced apoptosis.(omitted)

Doenjang (Korean fermented soybean paste) is one of important fermented foods in Korea. Doenjang has been traditionally manufactured from meju which is fermented rectangular shape of crushed cooked soybeans. The main microorganisms involved for meju fermentation are Bacillus subtilis and molds such as Rizopus sp., Mucor sp. and Aspergillus sp. We have already reported that Doenjang is free from mycotoxin, especially, aflatoxin B$_1$contamination during the manufacturing process of the Deonjang.(omitted)

GCP is a novel functional food obtained from the extracts of soybean isoflavone fermented with basidiomycetes mycelia. The enzyme reaction makes GCP containing high concentration of isoflavone aglycons, particularly for genistein and high content of polysaccharides. GCP exerts its anti-tumor activities by anti-angiogenesis and induction of apoptosis in cancer tissues and by enhancement of immune responses in immune system.(omitted)

Panax ginseng C. A. Meyer has been the most highly recognized medicinal herb in the Orient. The prolonged administration of red ginseng extract significantly inhibited the incidence of hepatoma and also proliferation of pulmonary tumors induced by aflatoxin B$_1$and urethane. Statistically significant anticarcinogenic effects were observed in powders and extract of 6 year-dried fresh ginseng, 5 and 6 year-white ginseng and 4, 5 and 6 year-red ginseng by 9 week medium-term anticarcinogenicity test using benzo［a］pyrene (Yun's model).(omitted)

Pomegranate (Punica granatum) is one of the worlds most ancient fruits, and also one of the most botanically isolated, comprising a single family (Punicae) with its rare relative, Punica protopunica, a species limited in occurrence to the island of Socotra off the coast of Yemen. Pomegranate, though, is extremely well known, flourishes in many parts of the world, is traditionally prized for its medicinal properties and widely regarded as Symbol: of fecundity, longevity, spirituality and Medicine.(omitted)

Free radicals and oxidative stress playa crucial role in the pathophysiology of a broad spectrum of cardiovascular diseases including congestive heart failure, valvular heart disease, cardiomyopathy, hypertrophy, atherosclerosis and ischemic heart disease. We have demonstrated that IH 636 proanthocyanidin extract (GSPE) provides excellent protection against free radicals in both in vitro and in vivo models, and exhibits significantly better efficacy as compared to vitamins C, E and $\beta$-carotene.(omitted)

Based on the success of green tea as a cancer preventive, herbal medicines are now also attracting attention as potential sources of cancer preventive agents. Using inhibition of TNF-$\alpha$ release assay, we studied Acer nikoense (Megusurino-ki in Japanese): Inhibitory potential was found in the leaf extract, and the main active constituents were identified as geraniin and corilagin. The $IC_{50}$/ values for TNF-$\alpha$ release inhibition were 43 $\mu$M for geraniin and 76 $\mu$M for corilagin, whereas that for (-)-epigallocatechin gallate (EGCG)was 26 $\mu$M.(omitted)

Persistent cellular oxidative stress and enhanced lipid peroxidation (LPO) of PUFAs, leading to macromolecular damage and disruption of signaling pathways, are implicated in the development of human malignancies and other chronic degenerative diseases. LPO generates by oxidation of linoleic acid (LA) or arachidonic acid ($\omega$ -6 PUPAs) reactive aldehydes, such as trans-4-hydroxy-2-nonenal, which form etheno $\varepsilon$ -DNA adducts in a variety of human tissues and thus can contribute to diet-related cancers.(omitted)

8-Hydroxyguanine(oh$\^$8/Gua), an oxidative DNA adduct is a most easily and abundantly formed base modification. What we have known about oh$\^$8/Gua so far is that this DNA adduct mediates the mutagenesis and it is used as a useful marker of oxidative DNA damage. We found additional evidence and here present them: 1) oh$\^$8/Gua in DNA can trigger cell death by inducing cell cycle arrest and apoptosis and 2) it can be used to assess the oxidative damage of each individual gene.(omitted)

Significant evidence exists which demonstrates that inflammation predisposes and promotes the cancer process in humans. Chronic inflammation can induce cancer in a variety of organ sites, including bowel and lung. There is also firm evidence that induced cyclooxygenases and nitric oxide synthetases, prostaglandins, and inflammatory cytokines can promote and accelerate the carcinogenic process.(omitted)

Large bowel cancer is one of the major causes of increasing world-wide cancer mortality. Our group has found a variety of naturally-occurring and synthetic compounds which have chemopreventive potentials against the occurrence of large bowel cancers using animal models. Aberrant crypt foci (ACF) which develop in rodents soon after the carcinogen exposure have been used as a biomarker for screening effective agents for cancer chemoprevention.(omitted)

MAP kinase/ AP-1 signal transduction components are rapidly initiated by many extracellular stimuli, especially environmental carcinogens. We have investigated the role of MAP kinases (Erks, JNKs, and p38 kinases) and AP-1 signal transduction pathways in the process of cell transformation and carcinogenesis. Incubation of Cl 41 cells with tumor promoters such as TPA, EGF, arsenic, or TNF-$\alpha$ led to cell transformation and activation of MAP kinases.(omitted)

A wide array of phenolic substances, particularly those present in dietary and medicinal plants, have been reported to possess substantial anticarcinogenic and antimutagenic activities. The majority of naturally occurring phenolics retain antioxidative and anti-inflammatory properties which appear to contribute to their chemopreventive or chemoprotective activity. Inducible cyclooxygenase (COX-2) and nitric oxide synthase (iNOS) are important enzymes that mediate inflammatory processes.(omitted)

Cancer chemoprevention Chemoprevention with strategies using food phytochemicals is currently regarded ascompose one of the noticeable most visible and promising scientific fields for cancer control. A large body of data from both epidemiologic and rodent studies has demonstrated that the ingestion of various vegetables and fruits is occasionally beneficial for cancer risk reduction of cancer risks in humans.(omitted)

Nutrition influences cancer incidence and offers a variety of preventive dietary factors including non-nutritive plant metabolites. To identify novel potential chemopreventive agents, we have set up cell- and enzyme-based in vitro marker systems relevant for prevention of carcinogenesis in vivo. This experimental approach led to the identification of Xanthohumol (Xn), a prenylated chalcone from hop (Humulus lupulus L.) as a most promising broad-spectrum chemopreventive agent.(omitted)

The cytochrome P450 (P450) 1 family (1A1, 1A2, 1B1) is involved in the activation of many pro-carcinogens. Previously we characterized a number of synthetic bi- and polycyclic hydrocarbon acetylenes as selective-mechanism-based inhibitors of recombinent P450s 1A1, 1A2, 1B1 (Shimada et al., Chem. Res. Toxicol., 11, 1048-1056, 1998). We reported that the drug oltipraz is a mechanism-based indicator of P450 1A2 (Lagouet et al. Chem. Res. Toxicol., 13, 245-252, 2000).(omitted)

The inhibition of carcinogenesis by tea has been demonstrated in animal models on many organ sites. These include cancers of the skin, lung, oral cavity, esophagus, stomach, liver, small intestine, pancreas, colon, bladder, prostate, and mammary glands. The most well studied sites are skin and lung.(omitted)

The chemopreventive effect of tea against 2-amino-l-methyl-6-phenylimidazo［4, 5-b ］pyridine (PhIP)-DNA adduct formation and its mechanism were studied. Rats were exposed to freshly prepared aqueous extracts of green tea (3% w/v) as the sole source of drinking water for 10 days prior to administration with a single dose of PhIP (10 mg/kg body wt) by oral gavage. PhIP-DNA adducts in the liver, colon, heart, and lung were measured using the $^{32}$ P-postlabelling technique.(omitted)

The increasing evidence for the involvement of food borne HAs in the aetiology of human cancer has stimulated intense efforts to identify dietary constituents which protect against these compounds. About 280 articles on this topic have been published in the last 20 years, most of them were antimutagenicity studies with indicator cells that require addition of exogenous activation mix. The experimental models do not adequately reflect protective mechanisms that are active in vivo and may give misleading results.(omitted)

Heterocyclic aromatic amines (HCAs) are established genotoxic human cancer risks, that display their activity also in a number of animal models and in vitro. They are formed during the trying or broiling of creatinine-containing foods, mainly fish or meat. We established that mixing soy protein with ground meat blocks the formation of HCAs. we also observed that coating the surface of meat with polyphenols green or from black tea gives a dose - related reduction of the formation of HCAs.(omitted)

Residents of Qidong, Peoples Republic of China, are at high risk for development of hepatocellular carcinoma, in part due to consumption of foods contaminated with aflatoxins. Chlorophyllin, a mixture of semi-synthetic, water-soluble derivatives of chlorophyll that is used as a food colorant and over-the-counter medicine, has been shown to be an effective inhibitor of aflatoxin hepatocarcinogenesis in animal models.(omitted)

The carcinogens 2-amino-3-methylimidazo［4, 5-f］quinoline (IQ) and 1, 2-dimethylhydrazine (DMH) induce colon tumors in the Fisher 344 rat that contain mutations in Ctnnbl, the gene for b-catenin, but the pattern of mutation differs from that found in human colon cancers. In both species, mutations affect the glycogen synthase kinase 3$\beta$ (GSK-3$\beta$) consensus region of $\beta$-catenin, but whereas they directly substitute critical Ser/Thr phosphorylation sites in human colon cancers, the majority of mutations cluster around Ser$_{33}$ in the rat tumors.(omitted)d)

DNA damage is an essential step in the pathogenesis of cancer and probably of other chronic degenerative conditions related to cigarette smoke (CS), such as atherosclerosis, cardiomyopathies, etc. Although the major goal of primary prevention is to refrain from smoking, chemoprevention by means of dietary and pharmacological agents provides a complementary preventive strategy. In spite of its overwhelming epidemiological importance, experimental studies evaluating CS as a complex mixture are relatively scanty.(omitted)

In order for vitamin D to be active, it needs to get metabolized to 1, 25 (OH)$_2$D3. This active metabolite of vitamin D induces epithelial cell differentiation and is antiproliferative. However, at the efficacious concentration, the natural ligand for VDR is hypercalcemic and toxic to cells. Therefore, numerous analogs have been synthesized with the hope of generating a compound that retains vitamin D activity and is non-toxic.(omitted)

The Maori people were early New Zealand settlers of Polynesian descent. The incidence of non-infectious diseases appears to have been low in these people, perhaps in part due to the presence of protective chemical constituents within their food plant supply. Three of the tropical crops they introduced are still eaten here today: the sweet potato of kumara (Ipomoea batatas), the taro (Colocasia esculenta) and the cabbage tree or ti (Cordyline terminalis).(omitted)

Modulation of events characteristic of carcinogenesis or of cancer cells is being emphasized as a rational strategy to combat cancer. This is achieved through chemoprevention by a variety of agents. Phenolic compounds, particularly polyphenols, have been shown to be highly active in this regard. Certain cellular and molecular events relevant to carcinogenesis are modified by polyphenols. The present investigation has been carried out to examine some of these aspects.(omitted)

In the present study, we examined the chemopreventive effects of indole-3-carbinol (I3C), a constituent of cruciferous vegetables (the Family of Cruciferae) such as cabbages, cauliflowers and broccoli on multiple intestinal neoplasia (Min) genetic mouse model and on mouse colon carcinogenesis induced by azoxymethane (AOM) as well as on rat mammary carcinogenesis induced by 7, 12-dimethybenz［$\alpha$］anthracene (DMBA).(omitted)

Results from laboratory experiments indicate that induction of phase II enzymes by dietary constituents leads to inactivation of genotoxins. In animal studies glutathione S-transferase (GST) induction was paralleled by a reduction of chemically induced tumours. However data on induction of phase II enzymes in humans is scarce. Therefore we carried out intervention studies in which we investigated the effect of cruciferous vegetables on GST induction, and studied the effects of these vegetables on meat derived urinary mutagenicity.(omitted)

Indole-3-carbinol (I3C), one component of cruciferous vegetables (the Family of Cruciferae), has been shown to exert chemopreventive effects in liver, colon and mammary tissue, but there has been substantial evidence that consumption of I3C induces tumor promotion in some tissues. Our studies were investigated to examine the modifying effects of I3C in the 7, 12-dimethylbenz［a］anthracene (DMBA) induced rat mammary tumor model.(omitted)

Helicobacter pylori (H pylori) is now generally accepted to be strongly associated with the development of gastric cancer, as well as intake of some diets and food ingredients such as antioxident vitamins, salt, charred food, etc. To evaluate the association of dietary habits and H pylori infection and gastric cancer in Koreans, a hospital based case-control study was conducted.(omitted)

Kimchi is a traditional fermented vegetable food in Korea. There are about 187 varieties of Kimchi, depending on the ingredients and processing methods used, which are different in microbiological, nutritional, and biochemical characteristics. Much attention for Kimchi has been focused on health and life extension. Kimchi is fermented by the microorganisms which are originally present in the raw vegetable substances.(omitted)

Flavonols are polyphenolic compounds that are present in dietary plant-based foodstuffs and beverages (e. g. apple, onion, grape fruit, tea) and medicinal plants (e. g. Crategus, Ruta graveolens, Silybum marianum, Fagopyrum species) in high concentrations. They have been reported to exhibit a wide variety of biological effects, including anti-inflammatory, antiviral, antioxidant and free-radical-scavenging activities.(omitted)

Former studies dealing with combined effects caused by chemical compounds in the metabolically competent hepatoma cell line Hep G2 indicated that Hep G2 cells are useful and sensitive indicators for the identification of synergisms of promutagens, comutagens and antimutagens which are relevant in eukryontic (human) cells. In the present study we examined the modulation of DNA damages by the suspected antimutagens ascorbic acid, beta-carotene, alpha-naphthoflavone and beta-naphthoflavone in Hep G2 cells.(omitted)

The mutagenic and antimutagenic activities of catechin, hamamelitannin and two proanthocyanidin fractions prepared from the bark of Hamamelis virginia L. - a commonly used medicinal herb - were investigated in a human derived hepatoma (Hep G2) cell line using the single cell gel electrophoresis (SCGE, syn. Comet assay) for the detection of DNA-migration. The cells possess different phase I and phase II enzymes involved in the biotransformation of xenobiotics.(omitted)

The antimutagenicities of methanol extracts from traditional and commercial kochujang (Korean Red Pepper Soybean Paste) and their ingredients were evaluated in Salmonella/mammalian microsome assay system. The traditional kochujang showed higher antimutagenic effects than the commercial one against Ν-methyl-Ν'-nitro-Ν-nitrosoguanidine (MNNG) in the Salmonella typhimurium TA100, a base-pair substituted mutant strain.(omitted)

Antimutagenic effect of red pepper powder (RPP) produced in Korea depending on the varieties and producing districts were studied against Ν-methyl-Ν'-nitro-Ν-nitrosoguanidine (MNNG) in Ames test and SOS chromotest. The antimutagenic activities of green pepper, red pepper and different parts of dried red pepper were also evaluated in the same experimental systems.(omitted)

Antimutagenic effect of chungkookjangs prepared with the different variety of soybean and starter were studied against aflatoxin B$_1$ (AFB1) using Ames test and Ν-methyl-Ν'-nitro-Ν- nitrosoguanidine (MNNG) using SOS chromotest. Chungkookjang samples exerted the different antimutagenicity according to the prepared variety of soybeans in the Ames test using Salmonella typhimurium TA100. The chungkookjang manufactured with var.(omitted)

To develop an antimutagenic functional diet, the foods that have shown anticancer activity were mixed to make ready-to-eat powdered diets. The diets were prepared with various kinds of powdered cooked cereals, cooked legumes, oil seeds and sea tangles, and freeze-dried vegetables. The antimutagenic effects of methanol extracts from three mixed diets were investigated in the Ames test, SOS chromotest, and in vivo supravital staining micronucleus assay in the mice.(omitted)

Antimutagens, including diverse compounds of botanical origin, offer some promise of reducing the risk posed by exposure to mutagens. Caution is warranted, however, as there may sometimes be a delicate balance between antimutagenic effects and potentiating effects of the same compounds. We studied effects of the antimutagens spermidine (SPD) and cysteamine (CSM) on the genetic activity of the radiomimetic cancer chemotherapy drug bleomycin (BLM).(omitted)

Introduction: Bambara groundnut (Vigna subterranean) commonly eaten in Central and Southern Africa region where the incidence of gastric and liver cancer is high because of the consumption of contaminated food by mycotoxins, has been investigated for antitumorigenic activitly using the classical Ames test with some modifications.(omitted)

A wide array of natural products have been identified to possess potenital cancer chemopreventive properties. Of particular interest is Polyporus umbellatus frs.. that exhibits antimutagenic and cytotoxic effects. The crud drug "chorei" prepared from the dried fruit body of Polyporus umbellatus is used for kidney and other such disease. In the study, we are isolating the minor components of Chorei and examined their antimutagenic and cytotoxic effects.(omitted)

In the present study, the protective effect of Scutellaria baicalensis against DNA damage in HL-60 cells exposed to $^{60}$ Co ${\gamma}$-rays was evaluated using micronuclei formation and alkaline single cell gel electrophoresis (SCGE, comet assay). The frequency of micronuclei was decreased in groups treated with water extract (P＜0.01), polysaccaride fraction (P＜0.01) and methanol fraction (P＜0.01) before/after exposure to 200 cGy of ${\gamma}$-rays.(omitted)

Resveratrol (3, 5, 4'-trihydroxystilbene) is a naturally occuring molecule, synthesized by several plants in response to different stresses. Recently many studies performed in human and mammalian cells demonstrated the involment of resveratrol in the modulation of several biological processes (inhibition of lipidic peroxidation, platelet aggregation, estrogenic activity). It has also been found to possess scavenging and antioxidant properties (1).(omitted)

Inner shell of chestnut (Castanea Mollissima, Fagaceae) is well-known anti-wrinkle agent, which has been used for long time in the treatment of skin aging. In this study, the extract of chestnut inner shell (CMIE) and its major component, ellagic acid (EA), were studied for their protective effects against free radical generation and hydrogen peroxide-induced oxidative DNA damages in the mammalian cells.(omitted)

The relationship between selenium and signal molecules is not well elucidated yet. It was found that physiological concentration of selenite, less than 3 $\mu$M, reduced ASKl activity and induced of PI3-Kinase/Akt pathways in HT1080 cells. Duration of these signal molecules by selenite was much longer than that by growth factors and other stresses. The longer duration time of these signal molecules may be important to maintain normal functions against stresses.(omitted)

Oxidative stress plays an important role in the pathological process of neurodegenerative diseases. Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants, some of which may be neurotoxic. Our previous studies showed that 2,2',5,5'-TetracWorobiphenyl (PCB 52) induced apoptotic death in human neuronal SK-N-MC cells, which was demonstrated on gel electrophoresis by visualization of the proteolytic cleavages of $\beta$-catenin and poly (ADP-ribose) polymerase (PARP) and of the production of characteristic ladder patterns of DNA fragmentation.

Dopamine, a principal neurotransmitter in the central nervous system, accounts for 90% of total catecholamines. It serves as a precursor of certain hormones, melanins, noradrenalin and adrenalin. Parkinsonian disease (PD) is characterized by selective loss of dopaminergic neurons in the substantia nigra pars compacta and a significant dimunution in the neostriatal content of dopamine and its metabolites.(omitted)

Tetrahydropapaveroline (THP), a dopamine-derived 6, 7-dihydroxy-1-(3' ,4'-dihydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline, has been suspected as a possible dopaminergic neurotoxin to elicit Parkinsonism. Autooxidation or enzymatic oxidation of THP and subsequent generation of reactive oxygen species (ROS) may contribute to the degeneration of dopaminergic neurons induced by this isoquinoline alkaloid.(omitted)

Oxidative stress induced by reactive oxygen and/or nitrogen species has been considered as a major cause of cellular injuries in a variety of neurodegenerative disorders including Alzheimers disease (AD). Inflammatory as well as oxidative tissue damage has been associated with pathophysiology of AD, and non-steroidal anti-inflammatory drugs have been reported to have beneficial effects in the treatment or prevention of AD.(omitted)

The phthalates have been shown to produce hepatic peroxisome proliferation and certain peroxisome proliferators (PPs) are also known to increase the incidence of liver tumors in rodents. In this study we investigated the correlation between oxidative injury, changes in peroxisomal and microsomal enzymes and tumor formation in PP-treated rats.(omitted)

The anti-cardiovascular effect of estrogen replacement therapy in postmenopausal women is known to be associated with its role as an antioxidant, its ability to protect cells from DNA damage. Genistein concentrated polysaccharide (GCP) is a functional food produced by fermentation of soybean isoflavone extracts with Basidiomycetes, containing rich content of genistein aglycones. The aim of this study was to investigate the effect of GCP on oxidative DNA damage and plasma total antioxidant potential, comparing to the effect of estrogen.(omitted)

It is generally thought that continuous oxidative damage to DNA is a major contributor to the risk of cancer development. Epidemiological studies suggest that fruits and vegetables might reduce the risk of cancer through their antioxidant properties. This study was designed to investigate the protective effect of fruits and fruit juice consumption against the oxidative DNA damage in lymphocytes of healthy subjects. (omitted)

According to the epidemiological studies in chromium workers, hexavalent chromium is associated with the risk of lung cancer. Genotoxicity such as chromosome aberration, and cellular oxidative damages by reactive oxygen species produced by hexavalent chromium exposure may play an important role in the carcinogenesis process. We investigated the availabilities of several kinds of biological markers to assess the genotoxicity and oxidative damages from chromium exposure in Korean chromium plating workers.(omitted)

DNA mutations undoubtedly contribute to the onset of some life style-related diseases including cancer. Rapid and reliable methods to detect DNA mutations and to isolate mutants should have a great impact on this field. Activated inflammatory leukocytes are considered to play some important roles in carcinogenesis by generating reactive oxygen species (ROS). The purpose of the present study is to examine the relationship between leukocyte activation by TPA and mutagenesis.(omitted)

Peroxynitrite (ONOO), a potent cytotoxic oxidant formed by the reaction of nitric oxide (ㆍNO) and superoxide radical (ㆍO$_2$), reacts rapidly to cause of oxidization and nitration process. The importance of the regulation of ONOO$^{-}$ has been recently recognized because of the lack of specific endogenous enzymes against ONOO$^{-}$. Coffee that is a complex mixture containing a variety of components has been reported to have both beneficial and hazardous effects.

Peroxynitrite (ONOO$^{-}$) is one of cytotoxic species produced by the reaction between superoxide(ㆍ $O_2$$^{-}$) and nitric oxide (NO). The aim of this study was to characterize ONOO$^{-}$ scavenging constituents from herbs. Methanolic extract derived from one hundred fifty nine herbs were screened out for their ONOO$^{-}$ scavenging activities. It was investigated that about 33 herbs was excellent scavengers of ONOO$^{-}$. The extracts exhibited dose-dependent ONOO$^{-}$ scavenging activities.

Tilianin, purified from acrial part of Agastache rugosa Kuntze, reduces progression and may induce some regression of aortic foam cell formation in low density lipoprotein receptor deficient mice (LDLR -/- mice). We investigated whether tilianin can prevent high fat diet-induced atherosclerosis. Twenty-six male mice were divided into three groups.(omitted)

Silymarin, a polyphenolic flavonoid antiodant, has been shown to have anti-inflammatory, hepatoprotective, and anticarcinogenic effects. In the present study, we report the inhibitory effect of silymarin on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) mRNA expression in macrophages. In vivo administration of silymarin attenuated NO production of peritoneal macrophages in lipopolysaccharide (LPS)-treated mice.(omitted)

Prostaglandins and nitric oxide produced by inducible cyclooygenase (COX-2) and nitric oxide synthase (iNOS), respectively, have been implicated as important mediators in the process of inflammation and carcinogenesis. On this line, the potential COX-2 or iNOS inhibitors have been considered as anti-inflammatory and cancer chemopreventive agents.(omitted)

Proinflamamtory mediators such as prostaglandins (PGs), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) are known to be key mediators in pathogenesis of inflammatory diseases. Capsaicin, the major ingredient of hot pepper, is considered to elicit anti-inflammatory property. In this study, the effect of capsaicin on the prostaglandin E$_2$(PGE$_2$) production was investigated in murine peritoneal macrophages.(omitted)

Abnormal regulation of the inducible form of cyclooxygenase (COX-2) has been often observed in various types of cancerous and transformed cells. Recently, targeted inhibition of COX-2 is recognized as one of the promising strategies for the prevention or treatment of cancer as well as inflammation, As part of a program to evaluate the cancer chemopreventive potential of anti-inflammatory phytochemicals, we initially determined the COX-2 inhibitory activity of some naturally occurring diarylheptanoids structurally related to curcumin.(omitted)

Genistein has been shown to exert propective effects against chemically induced carcinogenesis in animals as well as malignant transformation in cultured cells, but molecular mechanisms of its chemopreventive or chemoprotective activities remain largely unresolved. In the present sturdy, we have investigated the effects of genistein on induction of cyclooxygenase-2 (COX-2) that plays an important role in the pathophysiology of carcinogenesis as well as in cellular response to inflammatory stimuli.(omitted)

There has been accumulating evidence for the association of inflammatory tissue damage with the process of cancer development. Cyclooxygenase (COX), an important enzyme involved in mediating the inflammation, catalyzes the formation of prostaglandins (PGs) from arachidonic acid. There are two isoforms of COX, designated as COX-l and COX-2. COX-l is a housekeeping enzyme which is constitutively expressed and is thought to be involved in maintaining physiological functions.(omitted)

Ginseng saponins (ginsenosides) have been regarded as principal components responsible for the majority of pharmacological activities exerted by ginseng. IH-901, an intestinal bacterial metabolite derived from the protopanaxadiol saponin of Panax ginseng C.A. Meyer, has been reported to have anti-tumor effects including inhibition of angiogenesis, invasion and metastasis, as well as induction of tumor cell apoptosis. (omitted)

Curcuma xanthorrhiza Roxb(Zingiberaceae) has been traditionally used in Indonesia for dietry and medicinal purposes. Xanthorrhizol is a sesquiterpenoid isolated from C. xanthorrhiza that has been known to possess anti-inflammatory and anticarcinogenic defects.(omitted)

Eukaryotic nuclear transcription factor, NF-B and cyclooxygenase-2 (COX-2) has been implicated in pathogenesis of many human diseases including tumor and are known to be activated by various external stimuli. Recently, increasing evidences have supported that L-ascorbic acid (LAA) is selectively toxic to some types of tumors at pharmacological concentrations as a prooxidant, rather than antioxidant.(omitted)

There are increasing evidences that L-ascorbic acid (LAA) is selectively toxic to some types of tumors at physiological concentrations as a prooxidant, rather than antioxidant. However, the mechanism by which LAA initiates cellular signaling toward cell death is still unclear. Therefore, to determine whether LAA might be useful for the treatment of human acute promyelocytic leukemia (APL), HL-60 cells, the effects of LAA on proliferation, redox system, MAPK and induction of apoptotic cascades were investigated.(omitted)

A previous study showed that sulfur amino acid deprivation (SAAD) potentiated cytotoxicity induced by arsenic (As) and that activation of ERKl/2, p38 kinase and JNK1 was responsible for the potentiation of As toxicity. In the present study, we found for the first time that deprenyl a selective monoamine oxidase B inhibitor prevented potentiation of As toxicity by SAAD in a dose-dependent manner.(omitted)

Genistein, a phytoestrogen derived from soy isoflavone, has been shown to exert anti-proliferative activities, and have cell arrest and apoptotic effects in cultured tumor cells. However, these properties may not show at the low concentrations of genistein. Present study examined the effect of different concentrations of genistein on cell proliferative proteins, cell cycle regulators or apoptosis related protein in comparison with different concentrations of estrogen or co-treatment with estrogen.(omitted)

Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a phytoalexin found in grapes and wines is a potent antioxidant with cancer-preventive properties, the mechanism by which resveratrol imparts cancer chemopreventive effect is poorly defined. The aim of the present study was to further elucidate the possible mechanisms by which resveratrol exerts its anti-proliferative action in cultured human lung cancer cells.(omitted)

$\beta$ -lapachone, the product of a tree (Tabebuia avellanedae) from South America, is known to exhibit various pharmacologic properties, the mechanisms of which are poorly understood. The aim of the present study was to further elucidate the possible mechanisms by which $\beta$-lapachone exerts its anti-proliferative action in cultured human prostate cancer cells.(omitted)

MCS-5A, novel Cdk inhibitor, has been reported that it has exerted cell cycle arrest action and apoptotic effect to the human promyelocytic leukemias cell. The purpose of this study is to verify these effects of MCS-5A on human promyelocytic leukemia (HL-60) cells and to clarify the action of mechanism on MCS-5A-inducing apoptosis.(omitted)

Capsaicin, a major pungent ingredient in red hot pepper, has long been used in food additives and drugs. We have previously reported that capsaicin induces apoptosis in Korean stomach cancer cell line, SNU-1. In the present study, the mechanism of capsaicin-induced apoptotic cell death was investigated in SNU-1. Treatment of capsaicin to SNU-1 produced dose-dependent increase of apoptotic cell death and ［Ca2＋］$_{i}$ concentrations.(omitted)d)

Cyclooxygenase-2 (COX-2) is an inducible enzyme expressed in response to a variety of proinflammatory agents and cytokines. COX-2 expression has been shown to be elevated in several different types of human cancer. The presence of oncogenic ras has been associated with constitutive induction of COX-2 in certain H-ras transformed cells, and COX-2 overexpression confers resistance to apoptosis.(omitted)

We have previously shown that H-ras, but N-ras, induces an invasiveness and cell motility in human breast epithelial cells (MCFl0A), while both H-ras and N-ras induce transformed phenotype. It has been recently shown that phosphatidylinositol 3-kinase (PI3K) plays an important role on cell migration. In the present study, we wished to investigate the functional role of PI3K in H-ras-induced invasive phenotype in MCF10A cells.(omitted)

One of the most frequent defects in human cancer is the uncontrolled activation of the ras-signaling pathways. We have previously shown that H-ras, but not N-ras, induces an invasiveness and motility in human breast epithelial cells (MCF10A), while both H-ras and N-ras induce transformed phenotype. Since migration plays a crucial role in invasive, we examined motility of MCF10A cells transformed with H-ras of N-ras.(omitted)

Bioflavonoids have been regarded as therapeutic agents for a wide range of disease including cancer. The increase of matrix metalloproteinases expression is a key event in several pathological conditions, e.g., dermal photocarcinogenesis, tumor initiation, invasion and metastasis. In this study, we investigated effects of quercetin, a major bioflavonoid in human diet, on matrix metalloproteinase (MMR)-1, MMP-2, MMP-3, MMP-9 mRNA expression during cellular aging in cultured human foreskin fibroblast. (omitted)

Gap junctional intercellular communication (GJIC) is a cellular event underlying the tumor promotion process and that treatment to prevent the down-regulation or to up-regulate GJIC is important in preventing tumor promotion. We evaluated the potential preventive effect of Mushroom Phellinus Linteus (PL) against the promoting action of hydrogen peroxide ($H_2O$$_2$) in WB-F344 rat liver epithelial cells.(omitted)

Resveratrol (trans-3, 4', 5-trihydroxystilbene), which is a polyphenolic compound found in a variety of plants such as grapes and wine, has been reported to have a variety of anti-inflammatory, anti-platelet, and anti-carcinogenic effects. Recently resveratrol was reported to serve as an estrogen agonist in MCF-7 cells Based on its structural similarity to diethylstilbestrol, a synthetic estrogen, we examined whether resveratrol and its derivatives might be estrogenic using stable MCF-7-ERE cells. (omitted)

Phytoestrogens produced naturally by either plants or their seeds are three main classes of phytoestrogens: isoflavone, lignan and coumestan. Phytoestrogens can have both agonist and antagonist action of estrogenic activity. It is believed that phytoestrogens with agonist and antagonist action of estrogenic activity may reduce the risk of breast cancer, in addition to may reduce the risk of osteoporesis by therapeutic agent of breast cancer.(omitted)

Manganese (Mn) intoxication causes a parkinsonian syndrome. It may be difficult to distinguish Mn-induced parkinsonism from idiopathic Parkinson disease (IPD). Neuropathological descriptions on the brains with Mn intoxication showed the preferential damage in the globus pallidus and substantia nigra pars reticularis.(omitted)

The effects of betaine or taurine on hepatotoxicity induced by lipopolysaccharide (LPS) were examined in adult male SD rats. Rats were provided with drinking water containing either 1 % betaine or taurine for 2 weeks prior to challenge with LPS (5 mg/kg, iv). Supplement of betaine or taurine protected the animals from induction of LPS hepatotoxicity as measured by changes in aspartate aminotrassferase (AST), alanine aminotransferase (ALT) activities and total bilirubin levels in serum, and hepatic glutathione contents.(omitted)

Effects of propargylglycine (PPG) treatment on the hepatic glutathione (GSH) synthesis were examined in adult male ICR mice. Administration of PPG (200 mole/kg, ip) to mice resulted in a complete inhibition of the hepatic cystathionine ${\gamma}$ -lyase (C ${\gamma}$ L) activity measured in cytosol fraction for 40 hr after the treatment. A single injection of PPG rapidly reduced the hepatic GSH levels, which appeared to be sustained at least for 40 hr.(omitted)

This study was designed to evaluate a repeated oral dose toxicity of Polyrhachis vicina Roger in 7-week-old Sprague-Dawley rats. Animals were orally administered with dosages of 0, 20, 100, and 500 mg/kg/day of Polyrhachis vicina Roger everyday for 26 weeks, respectively. There were no dose-related changes in clinical signs, body weight changes, food or water consumption, opthalmoscopy, and hematlogical and biochemical parameters by Polyrhachis vicina Roger treatment.(omitted)

To investigate the safety and toxicity of a recombinant human erythropoietin, YHB216, we performed 4-week repeated dose toxicity test in 4-month-old Beagle dogs. We injected intravenously everyday for 28 days with dosages of 0, 500, 2,500 and 12,500 I.U/kg body weight. There were not observed clinical signs or motality in the animals treated with YHB216. There were no significant changes in body weight, feed, or water consumption.(omitted)

This study was designed to evaluate an acute and subacute intravenous dose toxicity of a new cephalosporin antibiotic agent, IDC-7181 in 7-week-old Sprague-Dawley rats. IDC-7181 was intravenously injected to rats at dose levels of 0, 3.2, 16, 80, 400 and 2, 000 mg/kg/day for single dose toxicity study and at dose levels of 0, 10, 50 and 250 mg/kg/day for 4 week-repeated dose toxicity study. All rats survived throughout the study periods.(omitted)

This study was designed to evaluate a repeated intravenous dose toxicity of a new anticancer agent, SB extracted from Pulsatilla korean Nakai in Beagle dogs. Animals were intravenously injected with dosages of 0, 0.062, 0.25, and 1 mg/kg of SB everyday for 13 weeks, respectively. There were no dose-related changes in clinical signs, body weight changes, food and water consumptions, opthalmoscopy, and urine analysis. There were somewhat significant differences compared with control group in organ weight, biochemical examination, and hematology findings of animals treated with SB. However, these changes were not dose-related changes. Gross and histopathological findings revealed no evidence of specific toxicity related to SB. These indicate that intraveous maximum tolerated dose value of SB may be over 1mg/kg in rats.

This study was designed to evaluate a repeated dose toxicity of a new tsutsugamushi vaccine, MBRI-98305R in 4-month-old beagle dogs. Animals were intramuscularly injected with dosages of 283, 56.6, 14.15 and 0 $\mu\textrm{g}$/kg everyday for 4 weeks, respectively. There were no dose-related statistical significant changes in clinical signs, body weight changes, food or water consumption, opthalmoscopy, hematological findings and biochemical examination of all animals treated with MBRI-98305R.(omitted)

This study was to evaluate oral toxicity of meat originated from cloned cows in 7-week-old Sprague-Dawley rats. The meats were mixed with 2%, 10%. and 50% in basal diet and were fed to SD rats for 28 days, respectively. There were no changes in clinical signs, blood and urine analyses, change of body weight, and feed intake or water consumption in all animals treated with the meat mixtures.(omitted)

The acute toxicity study of MBRI-98304, a new Hepatitis B virus (HBV) immunotherapeutic agent, was performed in Sprague-Dawley rats (7 weeks old) and Beagle dogs (4 months old). MBRI-98304 was injected intramuscularly at a single dosage of 0, 20, 100, 500, 2, 500, and 12, 500 $\mu\textrm{g}$/kg in rats and 0, 200, 1, 000, and 5, 000 $\mu\textrm{g}$/kg in Beagle dogs for 2 weeks daily. There were no deaths or clinical signs.(omitted)

Paclitaxel is currently administered i.v. as a slow infusion of a solution of the drug in an ethanol: cremophor EL: saline admixture. However, poor solubilization and toxicity are associated with this drug therapy. We have tried to develop a new surfactant for paclitaxel to improve efficacy and reduce toxicity of solubilizer.(omitted)

This experiment tested whether in utero and lactational exposure to 4-nonylphenol (NP) alters mammary gland differentiation in the female offspring rat. Pregnant Sprague Dawley rats were administered NP (l0, 100 mg/kg), atrazine (l00 mg/kg), pesticide demonstrating antiestrogenic activity in mammary gland development, or vehicle (0.5% methyl cellulose) by oral gavage from gestation day 15-19.(omitted)

Endocrine disruptors have been implicated in carcinogenesis in animal studies, but carcinogenetic effects on human remain controversial. In order to examine the genotoxicity of two common endocrine disruptors, Bisphenol A and Diethylstilbestrol, cytogenetic endpoints including chromosome aberration(CA), sister chromatid exchange (SCE), micronuclei (MN) analyses and DNA damage by single cell gel electrophoresis (SCGE) were assayed.(omitted)

Polychlorinated biphenyls(PCBs) are members of the halogenated aromatic group of environmental pollutants. Because of their unique physical and chemical properties, notably their stability and widespread use, PCBs are sidely distributed and transported throughout the global environment. In fact, residues of PCBs have been identified in air, water, aquatic and marine sediments, and human tissue samples.(omitted)

The interaction of extremely low frequency magnetic field (ELF-MF) on the frequency of micronuclei (MN) induced by benzo(a)pyrene (BP) in human lymphocytes was examined. A 60 Hz ELF-MF of 0.8 mT field strength was applied for 24 hours either alone or with the tumour initiator, BP. The frequency of MN induced by BP increased in a dose-dependent manner.(omitted)

To investigate the genotoxic effect of 1, 1-dichloro-1-fluoroethane which was widely used as a cleaning solvent at the electronic part industry, the micronucleus frequencies were recorded by examining polychromatic erythrocytes in bone marrows of single i.p. injected mice at high doses and of the repeatedly inhaled rats for 13 weeks at relatively low concentrations.(omitted)

The mutagenic potency of a new antibiotics, IDC- 7181, was evaluated using the mutagenicity tests including Ames, chromosome aberration and micronucleus tests. In bacterial reversion assay, IDC-7181 did not show any mutagenic response in the absence or presence of S9 mixture with Salmonella typhimurium TA98, TAlOO, TA1535 and TA1537 and E. coli WP2uvrA-(100, 50, 25, 12.5 and 6.25 $\mu\textrm{g}$/plate).(omitted)

1,2-Dibromo-3-chloropropane (DBCP), a soil fumigant against nematodes, is a genotoxic carcinogen and also is classified by World Wildlife Fund as endocrine disruptors. DBCP has been extensively studied on genotoxicity, carcinogenicity, and damage in male reproductive-related organs. However, information on precise mechanism of mutagenesis and carcinogenesis of DBCP is yet unknown. Thus the mutation spectrum and mechanism of DBCP was determined in lacI transgenic Big Blu $e^{R}$ Rat2 fibroblast cell lines.(omitted)d)

Sophoricoside was isolated as the inhibitor of IL-5 bioactivity from Sophora japonica (Leguminosae). It has been reported to have an anti-inflammatory effect on rat paw edema model. To develope as an anti-allergic drug, genotoxicity of sophoricoside was investigated in bacterial and mammalian cell system such as Ames bacterial test, chromosomal aberration assay and single cell gel electrophoresis (Comet) assay.(omitted)

Atrazine, one of herbicide widely used in agriculture, is classified as a possible human carcinogen (2B group) that may cause breast and ovarian cancers by IARC, and is known as an endocrine disruptor. Atrazine has been subjected to broad ranges of genotoxicity tests with predominantly negative results, but reported conflicting results across two or more independent tests as well. This fact indicates that a more comprehensive genotoxicity assessment needs for atrazine.(omitted)

The CD95 (Fas, APO-1) is known to play a key role as a transmembrane cell surface receptor that mediates apoptosis of many cell types through binding with Fas ligand or cross-linking to agonistic anti-Fas antibody. Activation of CD95 provokes a potent and rapid responses in a variety of cell types by unknown mechanism.(omitted)

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental toxin that activates the aryl hydrocarbon receptor (AhR) and disrupts multiple endocrine signaling pathways by enhancing ligand metabolism, altering hormone synthesis, down regulating receptor levels, and interfering with gene transcription. And TCDD-mediated gene transactivation via the AhR has been shown to be dependent upon estrogen receptor (ER) expression in human breast cancer cells.(omitted)

Since hypoxia-inducible factor-lalpha (HIF-lalpha) and the arylhydrocarbon receptor (AhR) shared the AhR nuclear translocator (Arnt) for hypoxia- and AhR-mediated signaling, respectively, it was possible to establish the hypothesis that hypoxia could regulate Cyp1a1 expression.(omitted)

Human cytochrome B5 (CYB5) was coexpressed with cytochrome P450 1A2 (CYP1A2), NADPH-CYP450 reductase (CYPR) and Ν-acetyltransferase 2 (NAT2) in Chinese hamster ovary (CHO) cells. The expression of four proteins was determined by Western blot analyses. The introduction of cDNAs to CHO cells were transduced via retroviral vectors. The cytotoxicity assay of 2-aminoanthracene (2-AA) and aflatoxin B$_1$were approximately 4-fold more sensitive than CYB5 free cells.(omitted)

For a continuous expression of human cytochrome p450 3A5 (CYP3A5) and NADPH-cytochrome P450 reductase (CYPR) proteins, bicistronic construct (CYP3A5BC-LNCX2) was made using internal ribosome entry site (IRES). As for mammalian cell expression, we used pLNCX2 retroviral vector; and using calcium phosphate, plasmid transfer was achieved in 293GPG cell and transduced in Chinese hamster ovary (CHO) cell.(omitted)

The elucidation of the genetic changes of cholangiocarcinoma is very important for understanding the molecular mechanism of carcinogenesis and progression of cholangiocarcinoma. In order to identify the gains or losses of the copy number of DNA sequence in cholangiocarcinoma, we used comparative genomic hybridization to study 33 cases of cholangiocarcinoma. The whole DNAs from each tumor tissue were labeled with different fluorochromes and then simultaneously hybridized to normal metaphase spread chromosomes.(omitted)

Although the incidence rates of gastric cancer and liver cancer, the most common cancers in Korea, are tending decrease, lung cancer is on the increase every year as cause of cancer death as well as incidence rate in Korea. And cigarette smoke is believed to be responsible for 90% of lung cancer. Many investigators have reported an association between genetic polymorphism of cytochromes P-450 (CYPs) or glutathoine S-transferase (GSTs) and susceptibility to lung cancer.(omitted)

A murine local lymph node assay (LLNA) has been developed as an alternative to guinea pig models for contact sensitization potential. However, a disadvantage of the LLNA is the need for the use of radioactive material. In this study, we aimed to investigate the development of non-radio isotopic endpoint for LLNA using immunohistochemistry.(omitted)

Preclinical test methods for allergenic potential chemicals has been widely used to assess human risks and has been developed. Recently, the murine local lymph node assay (LLNA) has been proposed as a prospective method to identify contact allergens and to replace conventional the guinea pig maximization test (GPMT). The objective of this study was to establish LLNA and to evaluate allergenicity of chemicals by LLNA. (omitted)

The inhibitory potentials of TCAs (imipramine, desipramine, amitriptyline, and nortriptyline) on phenytoin p-hydroxylation and probe metabolic pathways of each CYP isoforms were evaluated from incubation studies of human liver microsomes and cDNA-expressed cytochrome P450s in vitro in order to understand the mechanism of drug interaction between TCAs and phenytoin, a substrate of CYP2C9 and CYP2C19. (omitted)

Stereoselective metabolism and inhibitory potential of lansoprazole enantiomers were evaluated from the incubational studies of human liver microsomes and eDNA-expressed CYP isoforms in vitro. The formation of lansoprazole sulfone from both enantiomers appeared to be catalyzed by single and low affinity enzyme. Lansoprazole 5-hydroxylation, however, appeared to be mediated by two kinetically distinct CYP enzymes.(omitted)

The effect of CYP2C19 genetic polymorphism on the disposition of lansoprazole enantiomers was determined in order to evaluate the contribution of CYP2Cl9 in the stereoselective metabolism of lansoprazole. After single oral dose of 30mg lansoprazole racemate in 6 subjects with CYP2C19 PM genotype and 6 with EM genotype, the plasma concentrations of R-enantimers were consistently higher than those of S-enantiomer in boty EM and PM subjects.(omitted)

No report has been addressed to the CYP isoforms catalyzing chlorpropamide, a structural analogue of tolbutamide. To evaluate enzyme(s) mediating formation of 2-hydroxycWorpropamide, a major metabolite and identified by LC/Mass and NMR, incubation studies using human liver microsomes and cDNA expressed CYP were performed on the presence or absence of selective inhibitors of each CYP isoform. (omitted)

Both hypoxia and insulin induce same target genes including vascular endothelial growth factor (VEGF), glycolitic enzymes and glucose transporters. However these two signals eventually trigger quite different metabolic pathways. Hypoxia induces glycolysis for anaerobic ATP production, while insulin increase glycolysis for lipogenesis and energy storage. Hypoxia-induced gene expression is mediated by Hypoxia-inducible Factorl (HIF-1) that consists of HIF-1 $\alpha$ and $\beta$ subunit.(omitted)

The matrix metalloproteases (MMPs) play important roles in metastasis and invasion in various cell types. An endogenous inhibitor of MMP, tissue inhibitor of metalloprotease-2 (TIMP-2), has high specificity for MMP-2. An imbalance between MMP-2 and TIMP-2 causes the degradation of the extracellular matrix associated with pathological events including invasion and metastasis. Since TIMPs are secreted molecules, they have the potential to be used for gene therapy of certain tumors. (omitted)

Transforming growth factor- $\beta$ (TGF- $\beta$), a hormonally active polypeptide found in normal and transformed tissue, is a potent regulator of cell growth and differentiation. In this study, we wished to establish an in vitro bioassay system to seek the most sensitive method that can measure TGF- $\beta$ activity.(omitted)

Stable MCF-7-ERE cells, in which pERE-Luc reporter gene has been stably integrated into the genome of the MCF-7 cells, were used to detect the estrogenic activity of various dietary flavonoids.in either pure chemical or mixtures. Estradiol (E2) induced luciferase activity in dose dependent manner and this activity was inhibited by tamoxifen (Tam) concomitant treatment.(omitted)

Background and Aim: Transitional cell carcinoma (TCC) of the bladder represents the fifth most prevalent malignancy in Western population, with peak incidence found in males of the 50- to 70-year-old age group. A major problem in the management of bladder cancer is the low sensitivity of a large proportion (approximately 40%) among bladder tumors to chemotherapy and the high risk for recurrence of bladder tumors after transurethral resection.(omitted)