Journal of Cancer Prevention最新文献

This study was conducted to confirm the performance of the microRNA (miRNA) biomarker combination as a new breast cancer screening method in Korean women under the age of 50 with a high percentage of dense breasts. To determine the classification performance of a set of miRNA biomarkers (miR-1246, 202, 21, and 219B) useful for breast cancer screening, we determined whether there was a significant difference between the breast cancer and healthy control groups through box plots and the Mann-Whitney U-test, which was further examined in detail by age group. To verify the classification performance of the 4 miRNA biomarker set, 4 classification methods (logistic regression, random forest, XGBoost, and generalized linear model plus random forest) were applied, and 10-fold cross-validation was used as a validation method to improve performance stability. We confirmed that the best breast cancer detection performance was achievable in patients under 50 years of age when the set of 4 miRNAs were used. Under the age of 50, the 4 miRNA biomarkers showed the highest performance with a sensitivity of 85.29%, specificity of 93.33%, and area under the curve (AUC) of 0.961. Examining the results of 4 miRNA biomarkers was found to be an effective strategy for diagnosing breast cancer in Korean women under 50 years of age with dense breasts, and hence has the potential as a new breast cancer screening tool. Further validation in an appropriate screening population with large-scale clinical trials is required.

Activation of the COX-2/microsomal prostaglandin E synthase-1 (mPGES-1)/prostaglandin E₂ (PGE₂) signaling axis is a hallmark of many cancers, including colorectal cancer, prompting the implementation of prevention strategies targeting COX-2 activity. We have previously shown that targeting the downstream terminal PGE₂ synthase, mPGES-1 (Ptges), specifically reduces inducible PGE₂ formation without disrupting synthesis of other essential prostanoids, thereby conferring dramatic cancer protection against colon carcinogenesis in multiple mouse models. In order to accelerate its development as a viable drug target, and to better understand the mechanisms by which PGE₂ influences colon carcinogenesis, we recently developed a conditional Ptges knockout mouse model (cKO). To evaluate the functional role of Ptges directly within the colonic epithelia, cKO mice were crossed with carbonic anhydrase 1 (Car1)-Cre mice (cKO.Car1), and colon tumors were induced using the azoxymethane/dextran sodium sulfate protocol. Unexpectedly, epithelial-specific blockade of Ptges failed to protect mice against colon tumor development. Further studies using the cKO mouse model will be necessary to pinpoint the cell type-specific location of mPGES-1 and its control of inducible PGE₂ formation that drives tumor formation in the colon.

The gut microbiota interacts with the host gut environment, which is influenced by such factors as sex, age, and host diet. These factors induce changes in the microbial composition. The aim of this study was to identify differences in the gut microbiome of Fisher-344 (F344) rats fed a high-fat diet (HFD), depending on their age and sex. Fecal microbiomes from 6-, 31-, and 74-week-old, and 2-year-old both male and female rats (corresponding to 5-, 30-, 60-, and 80-year-old humans) were analyzed using 16S rRNA gene sequencing, phylogenetic investigation of communities by reconstruction of unobserved states, and enterotype (E) assessment. Moreover, the effect of an HFD on colonic epithelial cells was measured using real-time quantitative PCR. Alpha diversity decreased in the HFD group regardless of age and sex. Based on the enterotype clustering of the whole fecal microbiome, clusters from male rats were divided into E1 and E2 enterotypes, while clusters from female rats were divided into E1, E2, and E3 enterotypes. The female E3 group showed a significantly high abundance in the Ruminococcus genus and expression of Tlr2 mRNA, which may reflect compensation to the HFD. Moreover, the female E3 group showed a lower ratio of opportunistic pathogenic strains to commensal strains compared to the female E2 group. Administration of an HFD influenced the rat fecal microbiota in all assessed age groups, which could be further differentiated by sex. In particular, female rats showed a compensatory enterotype response to an HFD compared to male rats.

Human epidemiological and animal studies have demonstrated that excess iron is a risk for cancer. The responsible mechanisms are: 1) increased intracellular iron catalyzes the Fenton reaction to generate hydroxyl radicals, leading to mutagenic oxidative DNA lesions; 2) iron is necessary for cellular proliferation as cofactors of many enzymes. Thus, iron-excess milieu promotes selecting cellular evolution to ferroptosis-resistance, a major basis for carcinogenesis. Ferritin is a 24-subunit nanocage protein required for iron storage under the regulation of the iron-regulatory protein (IRP)/iron-responsive element (IRE) system. Ferritin is a serum marker, representing total body iron storage. However, how ferritin is secreted extracellularly has been unelucidated. We recently discovered that an exosomal marker CD63 is regulated by the IRP/IRE system and that iron-loaded ferritin is secreted as extracellular vesicles under the guidance of nuclear receptor coactivator 4 (NCOA4). On the other hand, we found that macrophages under asbestos-induced ferroptosis emit ferroptosis-dependent extracellular vesicles (FedEVs), which are received by nearby mesothelial cells, resulting in significant mutagenic DNA damage. Therefore, cells, including macrophages, can share excess iron with other cells, via iron-loaded ferritin packaged in extracellular vesicles as safe non-catalytic iron. However, similar process, such as one involving FedEVs, may cause accumulation of excess iron in other specific cells, which may eventually promote carcinogenesis.

Mitochondrial fission regulator 2 (MTFR2) is associated with mitochondrial fission, while few studies have assessed the associations between MTFR2 expression and clinical characteristics or prognosis of esophageal squamous cell carcinoma (ESCC). In this study, we compared the expression of MTFR2 in 6 ESCC tumors and relative normal tissues by immunohistochemistry (IHC). To assess the effect of MTFR2 expression on clinicopathologic characteristics and survival, 115 paraffin embedded ESCC tissue samples were assessed by IHC staining. Furthermore, the association between clinicopathological properties and MTFR2 expression in patients with ESCC was examined. The survival analysis was performed using the Cox regression models. We found that MTFR2 expression was significantly increased in ESCC tumors compared with normal esophageal epithelial cells. IHC analysis of 115 paraffin embedded ESCC tumor specimens of the patients showed that the expression of MTFR2 was significantly associated with clinical stage (P < 0.001), tumor classification (P < 0.001), histological grade (P < 0.001), and other clinicopathological characteristics. Both univariate and multivariate analyses showed that MTFR2 expression was inversely correlated with the survival of ESCC patients. In conclusion, the expression of MTFR2 is significantly associated with clinicopathologic characteristics and prognosis of ESCC. Thus, MTFR2 expression could serve as a potentially important prognostic biomarker and clinical target for patients with ESCC.

[This corrects the article on p. 183 in vol. 26, PMID: 34703821.].

Cancer is one of the most frequently diagnosed diseases, and despite the continuous efforts in searching for new and more effective treatments, its morbidity and mortality remain a significant health problem worldwide. Calorie restriction, a dietary manipulation that consists in a reduction of the calorie intake, is gaining attention as a potential adjuvant intervention for preventing and/or fighting cancer. Several forms of energy reduction intake, which includes caloric restriction tout-court, dietary restrictions, and intermittent fasting, are being explored for their ability to prevent or slow down cancer progression. Additionally, another anti-cancer approach being under investigation relies on the use of nutraceuticals known as "Caloric Restriction Mimetics" that can provide caloric restriction-mediated benefits without subjecting the patients to a strict diet. Preclinical in vitro and in vivo studies consistently show that diet modifiers reducing the calorie have impact on tumor microenvironment and cancer metabolism, resulting in reduced growth and progression of cancer. Preliminary clinical studies show that patients subjected to a reduced nutrient/energy intake experience improved outcomes from chemo- and radiotherapy while better tolerating the side effects. Here, we review the state of the art on the therapeutic potential of calorie restriction and of caloric restriction mimetics in preventing or retarding tumor development by modulating a subset of cellular processes. The most recent clinical progresses with caloric restriction mimetics in the clinical practice are also discussed.

Colorectal cancer (CRC) incidence and mortality are rising in individuals under age 50, termed early age onset (EAO) CRC. Lower endoscopy is recommended for all patients with unexplained iron deficiency anemia (IDA) or hematochezia to assess the EAO-CRC. For those without symptoms, professional societies recommend decreasing the age to start screening from 50 to 45. Primary care provider (PCP) knowledge and practices around EAO-CRC risk assessment and screening are unknown. We conducted a survey study in May, 2020 of multi-specialty PCPs from three large medical systems to assess PCP knowledge, risk stratification practices and barriers/facilitators they face to offer CRC screening in patients < 50. We conducted univariate analysis to assess factors associated with knowledge and diagnostic practices. Response rate was 27.7% (196/708). Although 77.6% of respondents were aware that EAO-CRC incidence is increasing, only 42.9% knew that EAO-CRC mortality is also increasing. Of note, 91.8% recommend starting average risk screening at age 50. For 40- to 49-year-old patients present with unexplained IDA or hematochezia, 71.9% and 50.5% of respondents, respectively, recommend a diagnostic colonoscopy. Trainees were less likely to be aware of rising EAO-CRC mortality (odds ratio, 0.42; 95% CI, 0.21 to 0.82) and non-internal medicine providers were less likely to recommend CRC screening in those with a first-degree relative with CRC (odds ratio, 0.82; 95% CI, 0.72 to 0.93). Ongoing education efforts will be required to improve recognition and management of high-risk symptoms, particularly among non-internists and trainees.