Adult Carcinogenesis Research Articles

Evaluation of heavy metal contamination of soil and the health risks in four potato-producing areas

Areas polluted by heavy metals in soil may pose a major risk to human health and ecological environment safety. In this study, 89 soil samples were collected from four potato producing areas (Libo, Chishui, Panxian and Weining) in Guizhou Province, China, and the concentrations of 9 soil heavy metals were analyzed and measured. The aims of this study was to evaluate the human health risk and pollution index of heavy metals in the soil of some potato-producing areas in Guizhou Province by using the geoaccumulation index method, pollution load index method and health risk assessment method. The results revealed that Igeo<0 in Libo and Chishui, Igeo>0 in Panxian except Pb, The Igeo of As and Sb were less than 0 in Weining, and other elements were polluted to varying degrees. The pollution load index is Panxian (1.47) > Weining (1.39) > Libo (0.67), Chishui (0.67), Libo and Chishui were generally no polluted, soils in Panxian and Weining were polluted. The health risks of potatoes through food ingestion are less than 1. In terms of carcinogenesis, the risk of human in each study area through the ingestion was Cr > As > Cd. Cr and As would be produced certain carcinogenic risk to human through the dermal contact. Cr had a strong carcinogenic risk to adults through the inhalation. In terms of non-carcinogenesis, children in each study area had a strong risk under the each pathways. The risk of carcinogenesis in adults through inhalation pathway is greater than that in children, and the risk of carcinogenesis and non-carcinogenesis in children through Ingestion and dermal contact pathway is greater than adults. The results of this study suggest that attention should be paid to the remediation of heavy metals in contaminated soil to protect human health.

CDKN2B deletion is essential for pancreatic cancer development instead of unmeaningful co-deletion due to juxtaposition to CDKN2A

Pancreatic cancer is among the deadliest malignancies; however, the genetic events that lead to pancreatic carcinogenesis in adults remain unclear. In vivo models in which these genetic alterations occur in adult animals may more accurately reflect the features of human cancer. In this study, we demonstrate that inactivation of Cdkn2b (p15ink4b) is necessary for induction of pancreatic cancer by oncogenic KRASG12D expression and inactivation of Tp53 and Cdkn2a in adult mouse pancreatic ductal cells (P60 or older). KRASG12D overexpression in these cells activated transforming growth factor-β signaling and expression of CDKN2B, which, along with CDKN2A, led to cellular senescence and protected cells from KRAS-mediated transformation via inhibition of retinoblastoma phosphorylation. These results show a critical role of CDKN2B inactivation in pancreatic carcinogenesis, and provide a useful adult animal model by genetic engineering via lentiviral delivery.

Wnt of the two horizons: putting stem cell self-renewal and cell fate determination into context.

The canonical Wnt/β-catenin pathway has long been associated with self-renewal and expansion of embryonic stem cells (ESCs). Recent studies have brought into question some earlier assumptions concerning the functional role that canonical Wnt signaling plays in self-renewal mechanisms by demonstrating clear effects on differentiation. In addition, Wnt is crucial for cell fate determination during embryogenesis. The seemingly contradictory data compiled over several years now point to a more complex system of organismal development by which the downstream effects of Wnt activity are largely determined by the context in which signaling occurs. This review will assess seemingly contradictory findings regarding Wnt signaling in either self-renewal or differentiation in ESCs and then explicate cellular scenarios that determine the context by which Wnt ligands exert their differential effects. Both physiological embryonic development and pathogenic adult carcinogenesis provide opportunities to gleam illuminating insights from stem or stem-like progenitor cells that place Wnt signaling at the center of important cellular decisions to expand or differentiate. The impact of heterogeneity, concentration, metabolic state, and the array of accessible interacting cofactors from various signaling pathways that regulate these functions in ESCs will be critically examined, and implications for early embryonic development and cancer biology will be explored.

Antral atrophy, intestinal metaplasia, and preneoplastic markers in Mexican children with Helicobacter pylori–positive and Helicobacter pylori–negative gastritis

Chronic inflammation and infection are major risk factors for gastric carcinogenesis in adults. As chronic gastritis is common in Mexican children, diagnosis of Helicobacter pylori and other causes of gastritis are critical for the identification of children who would benefit from closer surveillance. Antral biopsies from 82 Mexican children (mean age, 8.3 ± 4.8 years) with chronic gastritis (36 H pylori+, 46 H pylori-) were examined for gastritis activity, atrophy, intestinal metaplasia (IM), and immunohistochemical expression of gastric carcinogenesis biomarkers caudal type homeobox 2 (CDX2), ephrin type-B receptor 4 (EphB4), matrix metalloproteinase 3 (MMP3), macrophage migration inhibitory factor (MIF), p53, β-catenin, and E-cadherin. Atrophy was diagnosed in 7 (9%) of 82, and IM, in 5 (6%) of 82 by routine histology, whereas 6 additional children (7%) (3 H pylori+) exhibited aberrant CDX2 expression without IM. Significant positive correlations were seen between EphB4, MMP3, and MIF (P<.0001). Atrophy and follicular pathology were more frequent in H pylori+ biopsies (P<.0001), whereas IM and CDX2 expression showed no significant correlation with H pylori status. Antral biopsies demonstrating atrophy, IM, and/or aberrant CDX2 expression were seen in 21.95% (18/82) of the children, potentially identifying those who would benefit from closer surveillance and preventive dietary strategies. Biomarkers CDX2, EphB4, MMP3, and MIF may be useful in the workup of pediatric gastritis.

Epithelial-Connective Tissue Cross-Talk Is Essential for Regeneration of Intestinal Epithelium

Epithelial cells of the gastrointestine undergo a rapid cell-renewal and originate from stem cells throughout the life of the organisms. Previous studies have provided a solid body of evidence to show that the epithelial cell-renewal is under the strict control of cell-cell and cell-extracellular matrix (ECM) interactions between the epithelium and the connective tissue. Especially, the microenvironment around the stem cells called "niche" is thought to play important roles in this control, and its disruption leads to diseases or disorders such as cancer in the human gastrointestine. Although understanding how the niche affects the stem cells is clinically important, its mechanisms still remain mostly unknown at the molecular level, possibly due to difficulties in the identification of the stem cells in the gastrointestine. Recent progress in cell and molecular biology is gradually beginning to shed light on some of the key signaling pathways in the cell-renewal of the intestinal epithelium, such as Wnt/T-cell factor (TCF)/beta-catenin, Notch, Sonic hedgehog (Shh)/bone morphogenetic protein (BMP) signaling pathways, which are also involved in embryonic organogenesis and/or adult carcinogenesis. At present, only fragmentary information is available on their precise functions in the intestine. Nevertheless, there is a growing body of evidence that such signaling pathways have conservative functions in the intestine throughout terrestrial vertebrates, suggesting the usefulness of experimental animals to clarify molecular mechanisms regulating epithelial cell-renewal. In this article, I review some recent findings in this field, with particular focus on our studies using the Xenopus laevis intestine, where the stem cells form the mammalian-type intestinal epithelium under the control of connective tissue during metamorphosis. This Xenopus experimental system will certainly serve as a useful model for the study of the intestinal niche, whose clarification is urgently needed in regenerative medicine.