During cancer progression, some cells within the primary tumor may reactivate a latent embryonic program known as epithelial-to-mesenchymal transition (EMT). Through EMT, transformed epithelial cells can acquire the mesenchymal traits that seem to facilitate metastasis. Indeed, there is accumulating evidence that EMT and mesenchymal-related gene expression are associated with aggressive breast cancer subtypes and poor clinical outcome in breast cancer patients. More recently, the EMT program was shown to endow normal and transformed mammary epithelial cells with stem cell properties, including the ability to self-renew and efficiently initiate tumors. This link between EMT and stem cells may have numerous implications in the progression of breast tumors. The EMT process may facilitate the generation of cancer cells with the mesenchymal traits needed for dissemination as well as the self-renewal properties needed for initiation of secondary tumors. Breast cancer stem cells are resistant to many conventional cancer therapies, which can promote tumor relapse. Therefore, the generation of cancer stem cells by EMT may promote the development of refractory and resistant breast tumors. The purpose of this review is to summarize the findings related to EMT and stem cells in cancer progression and therapy resistance.

The epithelial-to-mesenchymal transition and cancer stem cells : a coalition against cancer therapies

PURPOSE
High circulating levels of proinflammatory cytokines cause anemia, perhaps by interacting with erythropoietin production or biological activity. We characterize the relationships of systemic inflammation, erythropoietin, and hemoglobin.


METHODS
Data are from the InCHIANTI (Invecchiare in Chianti, aging in the Chianti area) study population. A sample of 1270 persons aged 65 years or older and 30 men and 30 women from each age-decade 20 to 70 years were randomly selected from the residents in the Chianti, Italy, geographic area. Of the 1714 eligible persons, 1235 had complete data on inflammatory markers, erythropoietin, hemoglobin, potential causes of anemia, and other relevant covariates. Anemia was defined as hemoglobin less than 12 g/dL in women and less than 13 g/dL in men.


RESULTS
Independent of age, sex, and hemoglobin, the number of elevated inflammatory markers (C-reactive protein, interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha) was associated with progressively higher erythropoietin in non-anemic participants but lower erythropoietin in anemic participants. Findings were consistent across different causes of anemia. The threshold at which the effect of inflammation on erythropoietin reversed was close to 13.0 g/dL of hemoglobin.


CONCLUSIONS
Our findings suggest that anemia of inflammation evolves from a "pre-anemic" stage characterized by a compensatory increment of erythropoietin that maintains normal hemoglobin levels to a stage of clinically evident anemia in which erythropoietin levels are not high enough to maintain normal hemoglobin, possibly because of the inhibitory effect of inflammation on erythropoietin production. This hypothesis requires testing in a longitudinal study.

Iconographies supplémentaires de l'article : Proinflammatory state and circulating erythropoietin in persons with and without anemia

Microsomal epoxide hydrolase 1 (EPHX1): Gene, structure, function, and role in human disease.

Vitamin D has anticarcinogenic and immune-related properties and may protect against some diseases, including breast cancer Vitamin D affects gene transcription and may influence DNA methylation We studied the relationships between serum vitamin D, DNA methylation, and breast cancer using a case-cohort sample (1070 cases, 1277 in subcohort) of non-Hispanic white women For our primary analysis, we used robust linear regression to examine the association between serum 25-hydroxyvitamin D (25(OH)D) and methylation within a random sample of the cohort (“subcohort”) We focused on 198 CpGs in or near seven vitamin D-related genes For these 198 candidate CpG loci, we also examined how multiplicative interactions between methylation and 25(OH)D were associated with breast cancer risk This was done using Cox proportional hazards models and the full case-cohort sample We additionally conducted an exploratory epigenome-wide association study (EWAS) of the association between 25(OH)D and DNA methylation in the subcohort Of the CpGs in vitamin D-related genes, cg21201924 (RXRA) had the lowest p value for association with 25(OH)D (p = 00004) Twenty-two other candidate CpGs were associated with 25(OH)D (p < 005; RXRA, NADSYN1/DHCR7, GC, or CYP27B1) We observed an interaction between 25(OH)D and methylation at cg21201924 in relation to breast cancer risk (ratio of hazard ratios = 122, 95% confidence interval 110–134; p = 7 × 10−5), indicating a larger methylation-breast cancer hazard ratio in those with high serum 25(OH)D concentrations We also observed statistically significant (p < 005) interactions for six other RXRA CpGs and CpGs in CYP24A1, CYP27B1, NADSYN1/DHCR7, and VDR In the EWAS of the subcohort, 25(OH)D was associated (q < 005) with methylation at cg24350360 (EPHX1; p = 34 × 10−8), cg06177555 (SPN; p = 98 × 10−8), and cg13243168 (SMARCD2; p = 29 × 10−7) 25(OH)D concentrations were associated with DNA methylation of CpGs in several vitamin D-related genes, with potential links to immune function-related genes Methylation of CpGs in vitamin D-related genes may interact with 25(OH)D to affect the risk of breast cancer

/pdf/vitamin-d-dna-methylation-and-breast-cancer-1mqcc0fkiq.pdf

Vitamin D, DNA methylation, and breast cancer

Genetic polymorphisms and lung cancer risk: Evidence from meta-analyses and genome-wide association studies.

Objective To evaluate the correlation between the advanced lung cancer inflammation index (ALI) and the L3 skeletal muscle index (L3SMI) and their prognostic value in elderly patients with esophageal cancer (EC). Materials and methods The clinical data of 158 elderly patients with EC were collected retrospectively. The L3SMI measures the area of skeletal muscle at the level of the third lumbar (L3) vertebra using computed tomography (CT). A high L3SMI and low L3SMI group were created using sex-based quartiles. The ALI, prognostic nutrition index (PNI), and geriatric nutrition risk index (GNRI) were calculated according to standard laboratory protocols. Results The CT diagnostic criteria for senile sarcopenia in South China are height ≤32.96 cm2/m2 for females and height ≤35.4 cm2/m2 for males. The logistic regression analysis showed that a low L3SMI was significantly associated with a low ALI. Survival analysis revealed EC patients with a low L3SMI and a low ALI had poorer overall survival (OS) than patients with a high L3SMI and a high ALI. Univariate and multivariate Cox analyses showed that the L3SMI and ALI were independent predictors of EC prognosis in elderly individuals. Conclusion There was a significant correlation between the PNI, GNRI, ALI, and L3SMI. Overall, our findings show the L3SMI and ALI are clinical indicators that can potentially be used to independently predict the prognosis of elderly EC patients and display good predictive value.

/pdf/prognostic-significance-of-the-l3-skeletal-muscle-index-and-5fxx0qzkp9.pdf

Prognostic Significance of the L3 Skeletal Muscle Index and Advanced Lung Cancer Inflammation Index in Elderly Patients with Esophageal Cancer

Circulating tumor cells (CTCs) are a heterogeneous population of tumor cells with distinct clinical and biological properties. The aim of the present study was to evaluate the relationship between CTCs with the epithelial-mesenchymal transition phenotype (CTC EMT) and the proliferative marker Ki67, and their prognostic value in non-small cell lung cancer (NSCLC). CTCs were isolated from the peripheral blood of 84 NSCLC patients using the CanPatrolTM CTC enrichment method, and the expression of Ki67 in tumor tissues were detected by immunohistochemistry. Almost two-thirds (61/84) of the patients were positive for CTC EMT, and 55 (65.4%) patients had high in-situ expression of Ki67 (≥ 14%) in the tumor tissues. CTC EMT was not significantly associated with tumor size and differentiation, age, gender and histological type, but correlated with lymphatic metastasis, tumor stage and Ki67 overexpression. Furthermore, the CTC EMT+ NSCLC patients had a significantly lower recurrence-free survival (RFS) and overall survival (OS) compared to the negative patients. Similarly, Ki67 levels ≥ 14% were associated with a significantly lower RFS and OS. In conclusion, CTC EMT is significantly related to Ki67 expression, and is a risk factor of NSCLC.

Clinical significance of Ki67 and circulating tumor cells with an epithelial-mesenchymal transition phenotype in non-small cell lung cancer.

Recent studies report a correlation between excision repair cross-complementing group 2 (ERCC2) Lys751Gln polymorphism and an increased risk of lung cancer, but results are controversial and inconclusive. Thus, we conducted a comprehensive meta-analysis in order to assess the correlation between them. Our study uses an odds ratio (OR) with a 95% confidence interval (95% CI) to evaluate the strength of the association; we also performed Begg's funnel plot and the Egger's test to assess the publication bias of previous articles. Finally, our meta-analysis is comprised of 28 full studies, including 23,370 subjects (10,242 cases and 13,128 controls). Our overall research shows that ERCC2 Lys751Gln polymorphism carries an increased risk of developing lung cancer (C vs. A: OR = 1.160, 95% CI = 1.081-1.245, p = .000; CC vs. AA: OR = 1.252, 95% CI = 1.130-1.388, p = .000; CA vs. AA: OR = 1.152, 95% CI = 1.060-1.252, p = .001; CC+CA vs. AA: OR = 1.186, 95% CI = 1.089-1.292, p = .000; CC vs. CA+AA: OR = 1.196, 95% CI = 1.087-1.316, p = .000). In ethnic subgroup analyses, we find a significant risk among Caucasians (C vs. A: OR = 1.106, 95% CI = 1.048-1.166, p = .000; CC vs. AA: OR = 1.233, 95% CI = 1.103-1.378, p = .000; CC+CA vs. AA: OR = 1.113, 95% CI = 1.033-1.199, p = .005; CC vs. CA+AA: OR = 1.185, 95% CI = 1.069-1.313, p = .001) and among Asians under two genetic models (CA vs. AA: OR = 1.265, 95% CI = 1.034-1.549, p = .023; CC+CA vs. AA: OR = 1.252, 95% CI = 1.015-1.544, p = .036). These results were confirmed by similar findings, demonstrated by stratified analyses in study design and histological typing. This meta-analysis indicates that ERCC2 Lys751Gln polymorphism may lead to an increased susceptibility to lung cancer risk among Caucasians and Asians.

/pdf/association-between-ercc2-lys751gln-polymorphism-and-lung-14i8u223t2.pdf

Association Between ERCC2 Lys751Gln Polymorphism and Lung Cancer Risk: A Meta-Analysis Involving 23,370 Subjects

Background: Associations between the methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism and esophageal cancer risk have been reported in many articles recently, but results were controversial. Therefore the present meta-analysis was conducted to to provide a more precise estimation. Methods: Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of associations. Results: Finally, six casecontrol studies involving a total of 1,302 cases and 2,391controls for the A1298C polymorphism were included. The meta-analysis showed that significantly increased risk for Asians (CC versus AA, OR=3.799, 95%CI=1.541-9.365, P=0.004; CCversusCA+AA, OR=3.997, 95%CI=1.614-9.900, P=0.003) and Caucasians (CC versus AA, OR=1.797, 95%CI=1.335-2.418, P=0.000; CC+CA versus AA,OR=1.240, 95%CI=1.031-1.492, P=0.022; CCversusCA+AA, OR=1.693, 95%CI=1.280-2.240, P=0.000). In addition, there was an association with risk for both ESCC (CC versus AA, OR=2.529, 95%CI=1.688-3.788, P=0.000; CCversusCA+AA, OR=2.572, 95%CI=1.761-3.758, P=0.000) and esophageal adenocarcinoma (EAC) (CC versus AA, OR=1.592, 95%CI=1.139-2.227, P=0.007; CC+CA versus AA,OR=1.247, 95%CI=1.016-1.530, P=0.035; CCversusCA+AA, OR=1.466, 95%CI=1.069-2.011, P=0.018). Conclusion: This meta-analysis suggested associations of the A1298C polymorphism with increased risk of esophageal cancer in both Asians and Caucasians. In addition, we found that the MTHFR A1298C polymorphism might influence risk ofESCC and EAC in the overall studies.

http://koreascience.or.kr:80/article/JAKO201321365237794.pdf

Genetic Polymorphism of MTHFR A1298C and Esophageal Cancer Susceptibility: A Meta-analysis

The association between the microsomal epoxide hydrolase 1 gene (EPHX1) Tyr113His polymorphism and lung cancer and breast cancer risk has been reported in many recent studies, but there is no consensus among the results. Thus, we examined the association between the EPHX1 Tyr113His polymorphism and lung cancer through a meta-analysis. A comprehensive literature search was performed using the Pubmed and Embase databases. Odds ratios with 95% confidence intervals were used to assess the strength of associations. Our meta-analysis suggested that the Tyr113His polymorphism was associated with lung cancer risk in Asians under 3 genetic models, including a C vs T, CC vs TT, and recessive model. However, the risk was decreased in Caucasians under the genetic models, including a C vs T, CC vs TT, or CT vs TT, dominant, and recessive model. In contrast, there was no association with breast cancer risk for any of the genetic models. Our meta-analysis suggested that the EPHX1 Tyr113His polymorphism may be a risk factor for lung cancer in Asians, whereas it may be a decreased risk factor among Caucasians. However, this polymorphism was not found to be associated with breast cancer.

/pdf/quantitative-assessment-of-the-effects-of-the-ephx1-4rxh09a5q7.pdf

Yongyong Wang

Papers

Prognostic Significance of the L3 Skeletal Muscle Index and Advanced Lung Cancer Inflammation Index in Elderly Patients with Esophageal Cancer

Clinical significance of Ki67 and circulating tumor cells with an epithelial-mesenchymal transition phenotype in non-small cell lung cancer.

Association Between ERCC2 Lys751Gln Polymorphism and Lung Cancer Risk: A Meta-Analysis Involving 23,370 Subjects

Genetic Polymorphism of MTHFR A1298C and Esophageal Cancer Susceptibility: A Meta-analysis

Quantitative assessment of the effects of the EPHX1 Tyr113His polymorphism on lung and breast cancer.