Development of an Inflammation-Associated Colorectal Cancer Model and Its Application for Research on Carcinogenesis and Chemoprevention

Chronic inflammation is a well-recognized risk factor for development of human cancer in several tissues, including large bowel. Inflammatory bowel disease, including ulcerative colitis and Crohn's disease, is a longstanding inflammatory disease of intestine with increased risk for colorectal cancer development. Several molecular events involved in chronic inflammatory process may contribute to multistep carcinogenesis of human colorectal cancer in the inflamed colon. They include overproduction of reactive oxygen and nitrogen species, overproduction and upregulation of productions and enzymes of arachidonic acid biosynthesis pathway and cytokines, and intestinal immune system dysfunction. In this paper, I will describe several methods to induce colorectal neoplasm in the inflamed colon. First, I will introduce a protocol of a novel inflammation-associated colon carcinogenesis in mice. In addition, powerful tumor-promotion/progression activity of dextran sodium sulfate in the large bowel of ApcMin/+ mice will be described. Finally, chemoprevention of inflammation-associated colon carcinogenesis will be mentioned

Oral Carcinogenesis and Oral Cancer Chemoprevention: A Review

Oral cancer is one of the major global threats to public health. The development of oral cancer is a tobacco-related multistep and multifocal process involving field cancerization and carcinogenesis. The rationale for molecular-targeted prevention of oral cancer is promising. Biomarkers of genomic instability, including aneuploidy and allelic imbalance, are possible to measure the cancer risk of oral premalignancies. Understanding of the biology of oral carcinogenesis will yield important advances for detecting high-risk patients, monitoring preventive interventions, and assessing cancer risk and pharmacogenomics. In addition, novel chemopreventive agents based on molecular mechanisms and targets against oral cancers will be derived from studies using appropriate animal carcinogenesis models. New approaches, such as molecular-targeted agents and agent combinations in high-risk oral individuals, are undoubtedly needed to reduce the devastating worldwide consequences of oral malignancy

A Web application to estimate the climate change effects on agriculture in Thailand

A Web application was developed to estimate the effects of climate change on agriculture. We chose the northeast and north of Thailand as the target areas of this application, although most countries in the Asian monsoon region are agricultural areas. Northeastern Thailand is a rainfed farming area where rice and drought-tolerant crops are cultivated. Northern Thailand is a mountainous area where several types of vegetables are cultivated. The application identifies and recommends crops that can be grown based on the simulation results of a crop model DSSAT. The DSSAT was executed 365 times; the start date was moved forward one day each time. The effects of climate change were estimated by inputting meteorological data that reflects the influence of climate change. The most favorable start date and the yield are summarized and displayed as output. Application of this system to grid meteorological data required the shortening of execution time and handling a huge volume of data. These problems were solved using multithreading, StAX and Hadoop. The Web application with witch output data were presented was designed based on the assumption that it would be used by a farmer in the field with a 7-inch tablet.</jats:p

Cancer Chemoprevention by Citrus Pulp and Juices Containing High Amounts of β-Cryptoxanthin and Hesperidin

β-Cryptoxanthin, a carotenoid, and hesperidin, a flavonoid, possess inhibitory effects on carcinogenesis in several tissues. We recently have prepared a pulp (CHRP) and citrus juices (MJ2 and MJ5) from a satsuma mandarin (Citrus unshiu Mar.) juice (MJ). They contain high amounts of β-cryptoxanthin and hesperidin. We have demonstrated that CHRP and/or MJs inhibit chemically induced rat colon, rat tongue, and mouse lung tumorigenesis. Gavage with CHRP resulted in an increase of activities of detoxifying enzymes in the liver, colon, and tongue rats'. CHRP and MJs were also able to suppress the expression of proinflammatory cytokines and inflammatory enzymes in the target tissues. This paper describes the findings of our in vivo preclinical experiments to develop a strategy for cancer chemoprevention of colon, tongue, and lung neoplasms by use of CHRP and MJs

PPAR Ligands for Cancer Chemoprevention

Peroxisome proliferators-activated receptors (PPARs) that are members of the nuclear receptor superfamily have three different isoforms: PPARα, PPARδ, and PPARγ. PPARs are ligand-activated transcription factors, and they are implicated in tumor progression, differentiation, and apoptosis. Activation of PPAR isoforms lead to both anticarcinogenesis and anti-inflammatory effect. It has so far identified many PPAR ligands including chemical composition and natural occurring. PPAR ligands are reported to activate PPAR signaling and exert cancer prevention and treatment in vitro and/or in vivo studies. Although the effects depend on the isoforms and the types of ligands, biological modulatory activities of PPARs in carcinogenesis and disease progression are attracted for control or combat cancer development. This short review summarizes currently available data on the role of PPAR ligands in carcinogenesis

Pathobiology and Chemoprevention of Bladder Cancer

Our understanding of the pathogenesis of bladder cancer has improved considerably over the past decade. Translating these novel pathobiological discoveries into therapies, prevention, or strategies to manage patients who are suspected to have or who have been diagnosed with bladder cancer is the ultimate goal. In particular, the chemoprevention of bladder cancer development is important, since urothelial cancer frequently recurs, even if the primary cancer is completely removed. The numerous alterations of both oncogenes and tumor suppressor genes that have been implicated in bladder carcinogenesis represent novel targets for therapy and prevention. In addition, knowledge about these genetic alterations will help provide a better understanding of the biological significance of preneoplastic lesions of bladder cancer. Animal models for investigating bladder cancer development and prevention can also be developed based on these alterations. This paper summarizes the results of recent preclinical and clinical chemoprevention studies and discusses screening for bladder cancer

The modifying effects of green tea polyphenols on acute colitis and inflammation-associated colon carcinogenesis in male ICR mice.

Reactive oxygen species (ROS) have been implicated as mediators of intestinal inflammation and carcinogenesis. Although green tea polyphenols (GTP) have anticancer property as antioxidants they also generate ROS in vitro. In this study, we investigated the modifying effects of GTP on dextran sulfate sodium (DSS)-induced acute colitis and on 1,2-dimethylhydrazine (DMH) and DSS-induced colon carcinogenesis in male ICR mice. At sacrifice after 6 days, the colon shortening induced by 2% DSS was unchanged by 0.1% and 0.25% GTP, but increased by 0.5% and 1% GTP-containing diet. The expression of interleukin-1beta and macrophage-migration inhibitory factor in the DSS + 0.1% GTP group were lower than the DSS alone group, whereas the expression levels were increased in the DSS + 0.5% GTP and DSS + 1% GTP groups when compared with the DSS alone group. In a subsequent experiment to determine the effects of 0.01-1% GTP on inflammation-associated colon carcinogenesis induced by DMH/DSS, 0.5 and 1% doses of GTP failed to prevent the development of multiple colon tumors, rather, they tended to increase it. Our results thus indicate that the modifying effects of GTP on DSS-induced acute colitis and DMH/DSS-induced colon carcinogenesis depends upon its dosage and the expression of proinflammatory cytokines

Venous Thromboembolism After Removal of Retrievable Inferior Vena Cava Filters

The purpose of this study was to examine the incidence of new or recurrent venous thromboembolism (VTE) after retrieval of inferior vena cava (IVC) filters and risk factors associated with such recurrence. Between March 2001 and September 2008, at our institution, implanted retrievable vena cava filters were retrieved in 76 patients. The incidence of new or recurrent VTE after retrieval was reviewed and numerous variables were analyzed to assess risk factors for redevelopment of VTE after filter retrieval. In 5 (6.6%) of the 76 patients, redevelopment or worsening of VTE was seen after retrieval of the filter. Three patients (4.0%) had recurrent deep venous thrombosis (DVT) in the lower extremities and 2 (2.6%) had development of pulmonary embolism, resulting in death. Although there was no significant difference in the incidence of new or recurrent VTE related to any risk factor investigated, a tendency for development of VTE after filter retrieval was higher in patients in whom DVT in the lower extremities had been so severe during filter implantation that interventional radiological therapies in addition to traditional anticoagulation therapies were required (40% in patients with recurrent VTE vs. 23% in those without VTE; p = 0.5866 according to Fisher’s exact probability test) and in patients in whom DVT remained at the time of filter retrieval (60% in patients with recurrent VTE vs. 37% in those without VTE; p = 0.3637). In conclusion, new or recurrent VTE was rare after retrieval of IVC filters but was most likely to occur in patients who had severe DVT during filter implantation and/or in patients with a DVT that remained at the time of filter retrieval. We must point out that the fatality rate from PE after filter removal was high (2.6%)