Study on the Probiotics Regulating miRNA in H. Pylori-induced Wnt/β-catenin Gastric Carcinogenesis....
H. Pylori InfectionCarcinogenesisBackground. H. pylori has recognized as a type 1 carcinogen for gastric adenocarcinoma. Although H. pylori eradication promises to reduce the risk of gastric cancer, the regression rate of intestinal metaplasia (IM) after eradication is unsatisfactory. Therefore, to find the mechanism of IM persistent and a new strategy to improve IM regression are critical for reducing gastric cancer development. The canonical Wnt/beta-catenin signaling pathway upregulating cyclooxygenase-2 (COX-2) transcriptional activity involves gastric carcinogenesis after H. pylori infection. Investigators have established an in vitro model that H. pylori induces a cagA-dependent nuclear COX-2 expression in both GES-1 and AGS cells. MicroRNAs (miRNAs) are a class of widespread non-coding RNAs and have been shown to involve in the gastric carcinogenesis. Among these gastric cancer-related miRNA candidates, some were reported to interact with Wnt/β-catenin pathway. Clinically, H. pylori eradication plus celecoxib therapy results in about one-third cases being IM regression, which correlated to the nuclear β-catenin and COX-2 expression before treatment. Based on the probiotics ingestion can ameliorate H. pylori-induced inflammatory pathways, investigators hypothesis that H. pylori eradication with probiotics supplement may promote IM regression through regulating certain miRNAs and Wnt/β-catenin signaling. The aims of this 3-year grant will to establish the H. pylori induces the Wnt/beta-catenin and COX-2 signaling pathway in vitro. to investigate the effects and mechanisms of L. acidophilus and B. latis on H. pylori-induced Wnt/beta-catenin oncogenesis pathway. to study whether probiotics ingestion promote IM regression or ameliorate IM progression in H. pylori-infected patients after successful eradication therapy. Materials and Methods. A H. pylori (HP238) isolate strain, GES-1, and AGS cells will be used for in vitro study. The protein levels of cell tests will measured by western blot. The differences of miRNAs expression between monk, cells infected with H. pylori, and cells pretreated with probiotics than infected by H. pylori will be analyzed by next generation sequencing method. H. pylori-infected patients with IM will be randomly allocated to receive probiotics or controls, the 2nd endoscopy will be arranged at the 12th month to evaluate the IM status. Anticipated results. This study will to establish the H. pylori-induced Wnt/beta-catenin oncogenesis pathway in vitro. Furthermore, the effect and mechanism of probiotics inhibit the H. pylori-induced Wnt/beta-catenin signaling will be clarified. Finally, investigators will provide an evidence for the probiotics ingestion promote the rate of IM regression in patients after H. pylori eradication.
Inhibition of Oral Tumorigenesis by Antitumor B
Squamous Cell Cancer of the Oral CavityThis is a randomized, double-blinded, placebo-control window of opportunity study of Anti-tumor B versus placebo. Anti-tumor B is a botanical agent composed of six Chinese herbs: Sophora tonkinensis, Polygonum bistorta, Prunella vulgaris, Sonchus brachyotus, Dictamnus dasycarpus, and Dioscorea bulbifera.
Early Detection of Cancer Onset Based on Sensing Field Cancerization at the Organ Level in the Alimentary...
Esophageal AdenocarcinomaBarrett Esophagus5 moreThe investigators hypothesize that detection of field cancerization in the GI tract could be performed during endoscopy by performing Raman and scattering measurements. Together with the Technical University of Munich (TUM) and the Universidad Carlos III de Madrid (UC3M), the investigators have developed an investigational medical device that integrates probe-based Raman and scattering measurements for endoscopic purposes: the SENSITIVE system. During preclinical ex vivo studies, the investigators have established that measurements of the SENSITIVE system were able to discriminate between non-field cancerized tissue and field cancerized tissue. Considering these results, the investigators aim to assess the safety of in vivo Raman/scattering during endoscopy. Secondly, the investigators to assess the feasibility of this approach measurements to determine field cancerization in the alimentary tract during endoscopy through the SENSITIVE system.
Abnormal Food Timing and Circadian Dyssynchrony in Alcohol Induced Colon Carcinogenesis
Colorectal CancerThe purpose of this study is to study the impact of Western lifestyle, including moderate alcohol consumption and delayed eating patterns on studying individuals' susceptibility to colorectal cancer. This study aims to increase our ability to identify individuals at risk for colorectal cancer in the future. Each subject will experience four conditions (each for one week in duration with a week +/- 2 days wash-out in between): (1) "right-time eating" / no alcohol, (2) "right-time eating" / with alcohol, (3) "delayed-eating" / no alcohol, (4) "delayed-eating" / with alcohol. The order of experiments will be randomized [concealed randomization]. All subjects will undergo unprepped sigmoidoscopy after each week of intervention. In Aim 2, all subjects will have an option to undergo a 24h circadian assessment in the Biological Rhythms Research Lab after each week of intervention. The Investigator will assess (i) central circadian rhythms by collecting hourly salivary samples for melatonin assays and (ii) peripheral rhythm in the intestinal tract by buccal swabs once every 2h (12 time points) as well as by rectal sampling twice (every 12 hr). For Aim 3, sigmoidoscopy without sedation will be used to obtain colonic samples as the safe method compared to colonoscopy, which has some small but finite risks associated with the procedure (e.g, bleeding or perforation) as well as sedation.
Chemoprevention of Gastric Carcinogenesis
Gastric CancerGastric Intestinal MetaplasiaA clinical study of the efficacy of oral alpha-difluoromethylornithine (eflornithine or DFMO) in male and female subjects ages 30-60 with gastric premalignant lesions in two high risk regions of Latin America.
Evaluating Obesity-Mediated Mechanisms of Pancreatic Carcinogenesis in Minority Populations
Pancreatic CancerThis study will evaluate obesity-mediated mechanisms of pancreatic carcinogenesis in minority populations.
Changes Associated With H. Pylori and Gastric Carcinogenesis
Bacterial Infection Due to Helicobacter Pylori (H. Pylori)This is a research study for patients who currently have or previously had an H. pylori infection or who have gastric or esophageal cancer and who plan to undergo an endoscopy as part of their care. The purpose of this study is to find out how and why H. pylori infections can cause progression to gastric cancer and if it's possible for intervention prior to this progression.
Comparison of Expression of Carcinogenesis-related Molecular Markers in the Patients With Colon...
Colorectal CancerColorectal AdenomaA study of carcinogenesis-related molecular markers in the patients with colorectal cancer and colorectal adenoma.
Diet Composition, Weight Control, and Breast Carcinogenesis
Breast CancerIn the United States, overweight (BMI > 25 but < 30 Kg/m2) and obesity (BMI > 30Kg/m2) are increasing at epidemic rates. A significant association exists between being overweight or obese and breast cancer recurrence and survival. However, evidence continues to accumulate indicating that achieving or maintaining a healthy weight for height (Body Mass Index, BMI, 18.5-25Kg/m2) is associated with a reduced risk for breast cancer and with a decrease in breast cancer associated mortality. Despite this, there is a lack of randomized controlled trials exploring this association and how the process of fat loss or being successful in actually reaching a healthy weight for height differentially affects biomarkers for cancer recurrence. Many dietary approaches for weight loss are currently available to the public, and each purports to offer advantages. However, there is little scientific evidence to indicate how these dietary approaches, some of which vary markedly in the foods that they limit or exclude, affect biomarkers for breast cancer risk. In particular, it is not know whether the critical factor in relation to weight and breast cancer is simply weight loss (negative energy balance), irrespective of the manner in which it is achieved, or if certain dietary approaches affect breast cancer risk biomarkers more favorably than others. Published data from our laboratory suggest that dietary pattern does matter, and therefore the goal of this study is to investigate the effects of two popular weight loss dietary approaches that differ in the extent to which they limit carbohydrate or fat consumption (with effects on dietary glycemic load) compared to a usual care group on prognostic markers for cancer recurrence in postmenopausal breast cancer survivors. The investigators hypothesize that in addition to the anticipated effects of fat loss on circulating levels of bioavailable sex steroid hormones, that the effects of excess fat on breast cancer prognosis can be attributed to three interrelated metabolic processes that affect cancer progression: altered glucose metabolism, chronic inflammation and excessive cellular oxidation.
Broccoli Sprout Intervention in Qidong, P.R. China
Environmental CarcinogenesisThis study is a 12 week placebo-controlled Phase II broccoli sprout intervention to be conducted in Qidong, P.R. China. One thousand two hundred people from the farming townships will be screened and three hundred eligible individuals will be enrolled in the study. Participants will be randomized into two treatment groups: one will receive a juice beverage containing glucoraphanin- and sulforaphane-rich broccoli sprout extract, pineapple juice, lime juice, and water and the other will receive a placebo beverage containing pineapple juice, lime juice and water. Participants will drink their assigned beverage every evening and provide biweekly urine samples and monthly blood samples. The principal endpoints of this study are pharmacokinetic evaluation of elimination of glucoraphanin/sulforaphane and their metabolites in urine and pharmacodynamic evaluation through measures of urinary levels of exposure biomarkers for dietary and air-borne toxins, which are known to be high in this population.