Active clinical trials for "Carcinogenesis"

This study will examine the extent to which lower doses of a broccoli-derived beverage enhance the detoxication of air pollutants excreted in urine as compared to an maximal dose shown to be effective previously.

The primary purpose of the study is to evaluate the effectiveness of a naturally occurring clay substance (ACCS100) in reducing harmful effects of aflatoxin exposure (a carcinogen) and fumonisin (a cancer promoter). This clay substance contains of a variety of minerals including calcium, sodium, potassium, and magnesium. UPSN and similar aluminosilicate minerals have been regularly used as dietary supplements by humans and animals, and the safety of this naturally occurring clay substance has been tested in clinical trials. The FDA treats such minerals or nutritional supplements as a drug when tested for potential of lessening the likelihood of disease (i.e., potential for mitigating disease). This study involves the use of an investigational drug called Hydrated Sodium Calcium Aluminosilicate (ACCS100). "Investigational" means that the "drug" has not yet been approved by the U.S. Food & Drug Administration (FDA) for reducing harmful effects mycotoxin exposure in humans.

The goal of this observational study is to draw the characteristic maps of imaging omics, genomics, transcriptome, proteomics, pathological omics, metabolomics, etc. of the dynamic evolution of endometrial carcinogenesis in 100 patients with normal endometrium, 100 patients with atypical endometrial hyperplasia, and 100 patients with endometrial cancer; and then to explore the underlying molecular mechanism, and establish the database system for the dynamic evolution of endometrial carcinogenesis.

This study aims to assess the feasibility, acceptability, and the potential harm reduction of switching to potentially lower risk, oral nicotine pouches in adult smokers. Part One of this study aims to assess the interest of current smokers in switching to an e-cigarette device (i.e. JUUL) compared to alternative non-combustible tobacco products (i.e. smokeless tobacco/snus) and/or medicinal nicotine via survey. Part Two will consist of a pilot study of 30 non-treatment seeking adult smokers to investigate within-person changes in smoking behavior as a result of switching to different concentrations of oral nicotine pouch products (i.e. ZYN, 3mg and 6mg nicotine concentration). Additionally, by measuring bio-markers of tobacco exposure from baseline, this will allow the study to assess the potential for harm reduction in switching from cigarettes to oral nicotine pouches.

The long-term outcomes of branched-chain amino acid (BCAA) administration in patients undergoing hepatic resection remain unclear. The aim of this study is to assess the impact of oral supplementation with BCAA on the prevention for the development of liver tumorigenesis in patients undergoing liver resection.

The data of 460 gastric cancer patients who underwent curative gastrectomy with D2 lymph node dissection between January 2017 and February 2022 were analyzed. The clinicopathological features and prognosis of the patients with EBV-positive gastric cancers were compared with those of EBV-negative gastric cancers. Immunohistochemistry for epidermal growth factor receptor (EGFR), C-erb B2, Ki-67, and p53 was performed. Additionally, in situ hybridization was conducted to detect EBV, and microsatellite instability (MSI) analysis was used to assess the deficiency in mismatch repair (MMR) genes.

Colorectal cancer kills forty five people in France every day. Epidemiological studies suggest that two cases out of three could be prevented and show that processed meat intake is a consistent risk factor. The aim of this study is to understand how meat promotes cancer, to find protective strategies, and to make compelling dietary recommendations.

Neuroblastoma (NB) is the most common malignant tumor of infancy. Approximately 60% of NB patients are clinically diagnosed as the stage IV disease and have a very poor prognosis with the 5-year survival rate no more than 30%. Molecular markers of NB have great impacts on the tumor behavior. MYCN amplification is the most well-known marker to predict a poor outcome in NB patients. However, how MYCN affects the NB cell behavior remains unknown. In our preliminary studies, we performed a genome-wide analysis of the differential gene expression in 10 NB tumors with MYCN amplification and 10 with normal MYCN copy number. We found that aromatic hydrocarbon receptor (AHR) reversely correlated with the MYCN expression. This relationship was verified in 83 NB tumor samples. In addition, positive AHR expression by immunostaining of NB tumors predicted a favorable prognosis. These lines of evidence demonstrate that AHR not only relates to the MYCN expression but also plays an important role in the tumorigenesis of NB. Therefore in this project we aim at further studying the relationship between AHR and MYCN. In addition, the possible role of AHR in the tumorigenesis of NB will be clarified. Specifically, we propose a 3-year project with the following three aims: Aim I. Determine the molecular relationship between AHR and MYCN expression. AHR has been shown to suppress the E2F1 expression. E2F1 reversely has been found to upregulate the expression of MYCN. In our preliminary microarray study, we also found that the expression E2F1 positively correlated with the MYCN expression but inversely correlated with the expression of AHR. Therefore, NB cells will be transfected with AHR expression vector or AHR siRNA, then the associated E2F1 and MYCN expression will be examined to clarify if AHR could regulate MYCN expression via E2F1. Furthermore, the E2F1 levels will also be manipulated to determine if the effect of AHR on MYCN depends on E2F1. In addition, the E2F1 expression in NB tumor samples will also be examined to clarify its in vivo role. Aim II. Determine the effect of AHR expression on the NB cell behavior. The baseline AHR expression levels in several NB cell lines will be examined. AHR is then overexpressed by gene transfection in NB cells. The cell proliferation, migration, and differentiation after AHR overexpression are evaluated. Furthermore the AHR expression in normal neuron cells is also examined, and suppressed by siRNA to if downregulation of AHR could lead to cancer development. Aim III. Determine if AHR could be a target of gene therapy for NB. NB cells with either normal MYCN or MYCN amplification before and after AHR gene transfection are inoculated into nude mice to demonstrate the effect of AHR expression on NB cells behavior in vivo. AHR is then transfected into the wild type NB tumor to see if the tumor growth could be suppressed by AHR expression. Then wild type tumor and tumors transfected with AHR are subjected microarray analysis to compare with the human tumor data set for evaluation of gene expression changes along with differential AHR expression. Altogether, our studies will not only establish the relationship between AHR and MYCN, but also allow us to depict the functional role of AHR-MYCN interaction in the tumorigenesis of NB.

Colorectal Cancer is, in non-smokers for both sex, first cause of cancers mortality in Western country. The main risk factors associated with colorectal cancer depend of lifestyle, and processed meat and red meat could be involved in carcinogenesis by cytotoxic and genotoxic compound linked to lipid peroxidation and nitrosation. The aim of this study is to study the impact of the daily consumption of beef, processed or not, on lipid peroxidation induced heme iron ; and to study the impact of the daily consumption of ham, processed or not, on the nitrosilation induced heme iron.

Neuroblastoma (NB) is the most common malignant tumor of infancy. Approximately 60% of NB patients are clinically diagnosed as the stage IV disease and have a very poor prognosis with a 5-year survival rate of no more than 30%. The mechanism underlying the tumorigenesis of NB remains largely unclear. It has been suggested that the pathogenesis of NB is due to a failure of differentiation or apoptosis of the embryonic NB cells. Well-regulated glycosylation is essential for the normal development of the nervous system. Altered expression of glycosyltransferases with resulting dysregulated glycosylation of neuroblastic cells might lead to the development of NB. The β1,4-N-acetylgalactosaminyltransferase III (B4GALNT3) exhibits GalNAc transferase activity to form the GalNAcβ1,4GlcNAc (LacdiNAc or LDN) structure. The Drosophila B4GALNTA, homolog of human B4GALNT3, has been suggested to regulate the neuronal development. By immunohistochemical studies, we demonstrated that the expression of B4GALNT3 correlated well with histological grade of differentiation in 87 NB tumor samples. In addition, positive B4GALNT3 expression predicted a favorable patient's outcome. These evidences suggest that the regulation of glycosyltransferases is critical for the development of NB. To further explore the role of glycosyltransferases in the differentiation and development of NB, we propose a 3-year project with the following 3 major aims: Aim Ⅰ: Clarifying the effects of B4GALNT3 on NB cell behavior in vitro and in vivo. For further understanding the effects of B4GALNT3 on NB cells, NB cells with stable overexpression of B4GALNT3 are to be selected. Then NB cell phenotype and behavior changes after overexpression of B4GALNT3 are evaluated by in vitro assays as well as by a nude mice xenograft model. In addition, the expression of B4GALNT3 will be suppressed by siRNA, then the response of NB cells to ATRA-induced differentiation is evaluated. Aim Ⅱ: Clarifying the target proteins glycosylated by B4GALNT3 as well as their associated downstream pathways in vitro and in vivo. The possible proteins glycosylated by B4GALNT3 are evaluated by comparing differential protein expressions between B4GALNT3-transfected and mock-transfected NB cells using proteomics analysis. NB tumor samples with low and high B4GALNT3 expression levels are also subjected to proteomics analysis to explore the possible target proteins glycosylated by B4GALNT3 in vivo. After identifying the target proteins modified by B4GALNT3, the downstream pathways to affect NB cell differentiation will also be evaluated. Aim Ⅲ: Clarifying whether B4GALNT4, a family member of B4GALNT, plays a similar role as B4GALNT3, as well as how the expression of these enzymes are controlled epigenetically in human NB cell lines and tumor samples. The expression levels of B4GALNT4 in human NB samples are evaluated by RT-PCR and immunohistochemistry. The methylation status of the promoter sites of both B4GALNT3 and B4GALNT4 are examined in various NB cell lines as well tumor samples. Furthermore, NB tumor samples exhibiting high and low B4GALNT levels are subjected to microRNA array. Altogether, our studies will not only establish the functional role of the family of glycosyltransferases in the cell behavior of NB, but also illustrate how the expression of glycosyltransferases are regulated epigenetically and how the glycosyltransferases affect NB cell behavior. Therefore, our results might shed light to the oncogenesis of NB as well as target therapy of NB.