Publications by authors named "Keiji Wakabayashi"

Article Synopsis
  • Diet plays a crucial role in cancer development, with certain cooking methods like grilling contributing to mutagenic substances in food.
  • Researchers discovered two new harmful compounds, Trp-P-1 and Trp-P-2, that are produced when tryptophan is charred during cooking.
  • These compounds, along with over 10 other identified heterocyclic amines (HCAs), have been linked to cancer in various organs in animal studies and may also have implications for human cancer risk.
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Flavonoids, such as quercetin and kaempferol, and their glycosides, are widely distributed in vegetables and fruits. Sugimura, T. et al.

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Pierisin is a DNA-targeting ADP-ribosyltransferase found in cabbage white butterfly (). Pierisin transfers an ADP-ribosyl moiety to the 2-amino group of the guanine residue in DNA, yielding -(ADP-ribos-1-yl)-2'-deoxyguanosine (-ADPR-dG). Generally, such chemically modified DNA is recognized as DNA damage and elicits cellular responses, including DNA repair pathways.

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Pierisin-1 was serendipitously discovered as a strong cytotoxic and apoptosis-inducing protein from pupae of the cabbage butterfly against cancer cell lines. This 98-kDa protein consists of the N-terminal region (27 kDa) and C-terminal region (71 kDa), and analysis of their biological function revealed that pierisin-1 binds to cell surface glycosphingolipids on the C-terminal side, is taken up into the cell, and is cleaved to N- and C-terminal portions, where the N-terminal portion mono-ADP-ribosylates the guanine base of DNA in the presence of NAD to induce cellular genetic mutation and apoptosis. Unlike other ADP-ribosyltransferases, pieisin-1 was first found to exhibit DNA mono-ADP-ribosylating activity and show anti-cancer activity in vitro and in vivo against various cancer cell lines.

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Energy reserves, primarily stored in the insect's fat body, are essential for physiological processes such as reproduction and cocoon formation. However, whether these processes are mutually constraining is unknown. Here, we showed that cocoon-free silkworms accumulate amino acid constituents of silk proteins in the hemolymph and maintain lipid and sugar reserves in the pupal fat body by repressing the expression of sericin and fibroin genes in the middle and posterior silk glands, respectively, via butterfly pierisin-1A catalytic domain expression.

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Aspirin, a nonsteroidal anti-inflammatory drug, has been proven effective in a clinical trial of carcinogenesis blockade. However, various modes of action have been reported for these effects. Thus, in this study, we aimed to present reasonable mode of actions as a proof of concept for human trials, especially trials for patients with familial adenomatous polyposis (FAP).

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Unlabelled: Aspirin has gained great attention as a cancer preventive agent. Our previous study revealed that the low-dose aspirin prevents colorectal tumor recurrence in Japanese patients with colorectal adenomas and/or adenocarcinomas, whereas aspirin increases risks in smokers and has no effects on regular drinkers. Our recent study revealed that aspirin reduces polyp growth in Japanese patients with familial adenomatous polyposis (FAP).

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Background: Colibactin is a genotoxin produced by Escherichia coli and other Enterobacteriaceae that is believed to increase the risk of colorectal cancer (CRC) of their symbiosis hosts, including human. A peptidase ClbP is the key enzyme for activation of colibactin. Inhibition of ClbP is considered to impede maturation of precolibactin into genotoxic colibactin.

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Article Synopsis
  • Several aromatic amines, like -toluidine and -anisidine, can form harmful metabolites linked to bladder cancer.
  • In a recent study, it was discovered that these compounds can convert into cytotoxic dimer forms, which are involved in bladder carcinogenesis when incubated with a specific enzyme mix (S9).
  • The study highlighted differences in how quickly these dimers form and how stable they are, with those containing -anisidine showing the highest toxicity in bladder cancer cells compared to others.
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The steroidal alkaloid tomatidine is an aglycone of α-tomatine, which is abundant in tomato leaves and has several biological activities. Tomatidine has been reported to inhibit the growth of cultured cancer cells in vitro, but its anti-cancer activity in vivo and inhibitory effect against gastric cancer cells remain unknown. We investigated the efficacy of tomatidine using human gastric cancer-derived 85As2 cells and its tumor-bearing mouse model and evaluated the effect of tomatidine-rich tomato leaf extract (TRTLE) obtained from tomato leaves.

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Background/aim: Among colorectal cancer-associated intestinal microbiota, colibactin-producing (clb) bacteria are attracting attention. We aimed to clarify the interaction between clb Escherichia coli and normal colorectal epithelial cells in vivo and in vitro.

Materials And Methods: Five-week-old female Balb/c mice were divided in an untreated group, a group treated with clb E.

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The establishment of effective preemptive medicine against cancer is a very important issue. Now that the public is more likely to face the risk of cancer, with the era of genome medicine it is necessary to establish cancer chemopreventive agents as drugs as one of the active cancer prevention methods. To date, large clinical trials using cancer chemopreventive agents have yielded a limited number of beneficial results, and only tamoxifen and raloxifene have been approved as cancer-preventive drugs.

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Escherichia coli containing polyketide synthase in the gut microbiota (pks E coli) produce a polyketide-peptide genotoxin, colibactin, and are suspected to play a role in the development of colorectal neoplasia. To clarify the role of pks E coli in the early stage of tumorigenesis, we investigated whether the pks status of E coli was associated with the prevalence of colorectal neoplasia. This cross-sectional analysis of data from a prospective cohort in Izu Oshima, Japan included asymptomatic residents aged 40-79 years who underwent screening colonoscopy and provided a stool sample.

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Cigarette smoking and alcohol consumption are major risk factors for lifestyle-related diseases. Although it has been reported that the combination of these habits worsens risks, the underlying mechanism remains elusive. Reactive carbonyl species (RCS) cause chemical modifications of biological molecules, leading to alterations in cellular signaling pathways, and total RCS levels have been used as a lipid peroxidation marker linked to lifestyle-related diseases.

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Background: The Escherichia coli strain that is known to produce the genotoxic secondary metabolite colibactin is linked to colorectal oncogenesis. Therefore, understanding the properties of such colibactin-positive E. coli and the molecular mechanism of oncogenesis by colibactin may provide us with opportunities for early diagnosis or prevention of colorectal oncogenesis.

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Background: Colibactin-producing Escherichia coli containing polyketide synthase (pks E. coli) has been shown to be involved in colorectal cancer (CRC) development through gut microbiota analysis in animal models. Stool status has been associated with potentially adverse gut microbiome profiles from fecal analysis in adults.

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Background: The only established treatment for preventing colorectal cancer in patients with familial adenomatous polyposis (FAP) is colectomy, which greatly reduces patient quality of life. Thus, an alternative method is warranted. In this trial, we aimed to clarify the individual and joint effects of low-dose aspirin and mesalazine on the recurrence of colorectal polyps in Japanese patients with FAP.

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Colibactin is a polyketide-nonribosomal peptide hybrid secondary metabolite that can form interstrand cross-links in double-stranded DNA. Colibactin-producing has also been linked to colorectal oncogenesis. Thus, there is a strong interest in understanding the role colibactin may play in oncogenesis.

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Monocyclic aromatic amines, -toluidine (-Tol) and its structural analog -anisidine (-Ans), are IARC Group 1 and Group 2A urinary bladder carcinogens, respectively, and are involved in metabolic activation and DNA damage. Our recent study revealed that 2-methyl--(2-methylphenyl) benzene-1,4-diamine (MMBD), a -semidine-type homodimer of -Tol, was detected and identified in an reaction of -Tol with S9 mix and urinary samples of -Tol-exposed rats. Potent mutagenic, genotoxic, and cytotoxic activities were reported with MMBD, suggesting its involvement in urinary bladder carcinogenesis.

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Developing a use for the inedible parts of citrus, mainly peel, would have great environmental and economic benefits worldwide. Astaxanthin is a value-added fine chemical that affects fish pigmentation and has recently been used in healthcare products for humans, resulting in an increased demand. This study aimed to produce astaxanthin from a citrus, ponkan, peel extract using the yeast Xanthophyllomyces dendrorhous, which has the ability to use both pentose and hexose.

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The relative contribution of diet to colorectal cancer (CRC) incidence is higher than that for other cancers. Animal models have revealed that Escherichia coli containing polyketide synthase (pks E. coli) in the gut participates in CRC development.

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We examined the association of biological components in airborne particles, i.e., proteins and endotoxins, in outdoor air with asthma exacerbation in the Fukuoka metropolitan area, Fukuoka, Japan.

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Exposure to airborne particulate matter (PM) is related to the increased risk of several diseases, including chronic and allergic rhinitis. We have previously shown that atmospheric endotoxin level was positively associated with the number of emergency department visits for asthma even after adjusting for meteorological factors, suggestive of the significant association between atmospheric endotoxin level and asthma exacerbation. Whether atmospheric endotoxin level is related to inflammatory response induction is, however, unclear.

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