Black raspberries suppress colonic adenoma development in ApcMin/+ mice: relation to metabolite profiles
Freeze-dried black raspberries (BRBs) have demonstrated chemopreventive effects in a dietary intervention trial with human colorectal cancer patients. The aim of this study was to investigate BRB-caused metabolite changes using the ApcMin/+ mouse as a model of human colorectal cancer. Wild-type (WT) mice were fed control diet, and ApcMin/+ mice were fed either control diet or control diet supplemented with 5% BRBs for 8 weeks. Colonic and intestinal polyp size and number were measured. A non-targeted metabolomic analysis was conducted on colonic mucosa, liver and fecal specimens. Eight weeks of BRB treatment significantly ...
Source: Carcinogenesis - September 30, 2015 Category: Cancer & Oncology Authors: Pan, P., Skaer, C. W., Wang, H.-T., Stirdivant, S. M., Young, M. R., Oshima, K., Stoner, G. D., Lechner, J. F., Huang, Y.-W., Wang, L.-S. Tags: Original Manuscript Source Type: research
DNA repair by MGMT, but not AAG, causes a threshold in alkylation-induced colorectal carcinogenesis
This study demonstrates for the first time a non-linear dose–response for alkylation-induced colorectal carcinogenesis and reveals DNA repair by MGMT, but not AAG, as a key node in determining a carcinogenic threshold. (Source: Carcinogenesis)
Source: Carcinogenesis - September 30, 2015 Category: Cancer & Oncology Authors: Fahrer, J., Frisch, J., Nagel, G., Kraus, A., Dorsam, B., Thomas, A. D., Reissig, S., Waisman, A., Kaina, B. Tags: Original Manuscript Source Type: research
Aschantin targeting on the kinase domain of mammalian target of rapamycin suppresses epidermal growth factor-induced neoplastic cell transformation
This study reveals aschantin, a natural compound abundantly found in Magnolia flos, as a novel mTOR kinase inhibitor. Aschantin directly targeted the active pocket of mTOR kinase domain by competing with adenosine triphosphate (ATP), but not PI3K and PDK1. Aschantin inhibited epidermal growth factor (EGF)-induced full activation of Akt by phosphorylation at Ser473/Thr308, resulting in inhibition of the mTORC2/Akt and Akt/mTORC1/p70S6K signaling pathways and activation of GSK3β by abrogation of Akt-mediated GSK3β phosphorylation at Ser9. The activated GSK3β inhibited cell proliferation by c-Jun phosphorylatio...
Source: Carcinogenesis - September 30, 2015 Category: Cancer & Oncology Authors: Lee, C.-J., Jang, J.-H., Lee, J.-Y., Lee, M.-H., Li, Y., Ryu, H. W., Choi, K.-I., Dong, Z., Lee, H. S., Oh, S.-R., Surh, Y.-J., Cho, Y.-Y. Tags: Original Manuscript Source Type: research
MiR-17-92 cluster promotes hepatocarcinogenesis
In this study, we show that the miR-17-92 cluster is highly expressed in human hepatocellular carcinoma (HCC) tissues compared to the non-tumorous liver tissues by RT-PCR and in situ hybridization analyses. Increased miR-17-92 cluster expression in HCC tissues was further confirmed by analysis of the RNA-sequencing data of 319 patients available from the Cancer Genome Atlas (TCGA) Data Portal (https://tcga-data.nci.nih.gov/tcga/). To create an animal model that resembles enhanced miR-17-92 in the liver, we developed liver-specific miR-17-92 transgenic mice and the animals were treated with the hepatic carcinogen, diethylni...
Source: Carcinogenesis - September 30, 2015 Category: Cancer & Oncology Authors: Zhu, H., Han, C., Wu, T. Tags: Original Manuscript Source Type: research
LIFR functions as a metastasis suppressor in hepatocellular carcinoma by negatively regulating phosphoinositide 3-kinase/AKT pathway
Hepatocellular carcinoma (HCC) is one of the leading causes for cancer related mortality worldwide. Poor prognosis of HCC patients is mainly due to frequent metastasis and recurrence. Deregulation of metastasis suppressors in malignant cells plays critical roles during cancer metastasis. Thus, novel metastasis suppressors are urgently needed to be uncovered to shed new light on molecular mechanisms driving HCC metastasis. In the present study, decreased expression of leukemia inhibitory factor receptor (LIFR) was demonstrated in HCC, and its expression levels were even lower in HCC with metastasis. Downregulated LIFR expre...
Source: Carcinogenesis - September 30, 2015 Category: Cancer & Oncology Authors: Luo, Q., Wang, C., Jin, G., Gu, D., Wang, N., Song, J., Jin, H., Hu, F., Zhang, Y., Ge, T., Huo, X., Chu, W., Shu, H., Fang, J., Yao, M., Gu, J., Cong, W., Qin, W. Tags: Original Manuscript Source Type: research
Slc10a2-null mice uncover colon cancer-promoting actions of endogenous fecal bile acids
In this study, we exploited mice deficient in the ileal apical sodium-dependent bile acid transporter (ASBT, encoded by SLC10A2) in whom fecal bile acid excretion is augmented more than 10-fold. Wild-type and Asbt-deficient (Slc10a2 –/– ) male mice were treated with azoxymethane (AOM) alone to examine the development of aberrant crypt foci, the earliest histological marker of colon neoplasia and a combination of AOM and dextran sulfate sodium to induce colon tumor formation. Asbt-deficient mice exhibited a 54% increase in aberrant crypt foci, and 70 and 59% increases in colon tumor number and size, respecti...
Source: Carcinogenesis - September 30, 2015 Category: Cancer & Oncology Authors: Raufman, J.-P., Dawson, P. A., Rao, A., Drachenberg, C. B., Heath, J., Shang, A. C., Hu, S., Zhan, M., Polli, J. E., Cheng, K. Tags: Original Manuscript Source Type: research
The senescent microenvironment promotes the emergence of heterogeneous cancer stem-like cells
We reported previously that human epithelial cells that undergo telomere-driven chromosome instability (T-CIN) display global microRNA (miR) deregulation and develop migration and invasion capacities. Here, we show that post-crisis cells are not able to form tumors unless a senescent microenvironment is provided. The characterization of cell lines established from such tumors revealed that these cells have acquired cell autonomous tumorigenicity, giving rise to heterogeneous tumors. Further experiments demonstrate that explanted cells, while displaying differences in cell differentiation markers, are all endowed of enhance...
Source: Carcinogenesis - September 30, 2015 Category: Cancer & Oncology Authors: Castro-Vega, L. J., Jouravleva, K., Ortiz-Montero, P., Liu, W.-Y., Galeano, J. L., Romero, M., Popova, T., Bacchetti, S., Vernot, J. P., Londono-Vallejo, A. Tags: Original Manuscript Source Type: research
Antiangiogenic and antitumor activities of berberine derivative NAX014 compound in a transgenic murine model of HER2/neu-positive mammary carcinoma
In this study, we examined the anticancer properties of BBR and NAX014 in a transgenic mouse model which spontaneously develops HER2-positive mammary tumors. Repeated intraperitoneal injections of a safety dose (2.5mg/kg) of NAX014 delayed the development of tumors, reducing both the number and size of tumor masses. In vivo sidestream dark field videomicroscopy revealed a significant lower vessel density in mammary tumors from NAX014-treated mice in comparison with the control group. Immunohistochemical evaluation using CD34 antibody confirmed the reduced vessel density in NAX014 group. Statistically significant increase o...
Source: Carcinogenesis - September 30, 2015 Category: Cancer & Oncology Authors: Pierpaoli, E., Damiani, E., Orlando, F., Lucarini, G., Bartozzi, B., Lombardi, P., Salvatore, C., Geroni, C., Donati, A., Provinciali, M. Tags: Original Manuscript Source Type: research
Citrus consumption and risk of basal cell carcinoma and squamous cell carcinoma of the skin
Animal experiments have demonstrated the photocarcinogenic properties of furocoumarins, a group of naturally occurring chemicals that are rich in citrus products. We conducted a prospective study for citrus consumption and risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin based on data from 41530 men in the Health Professionals Follow-up Study (1986–2010) and 63759 women in the Nurses’ Health Study (1984–2010) who were free of cancers at baseline. Over 24–26 years of follow-up, we documented 20840 incident BCCs and 3544 incident SCCs. Compared to those who consumed cit...
Source: Carcinogenesis - September 30, 2015 Category: Cancer & Oncology Authors: Wu, S., Cho, E., Feskanich, D., Li, W.-Q., Sun, Q., Han, J., Qureshi, A. A. Tags: Original Manuscript Source Type: research
Distinct genotype-dependent differences in transcriptome responses in humans exposed to environmental carcinogens
Considering genetic variability in population studies focusing on the health risk assessment of exposure to environmental carcinogens may provide improved insights in individual environmental cancer risks. Therefore, the current study aims to determine the impact of genetic polymorphisms on the relationship between exposure and gene expression, by identifying exposure-dependently coregulated genes and genetic pathways. Statistical analysis based on mixed models, was performed to relate gene expression data from 134 subjects to exposure measurements of multiple carcinogens, 28 polymorphisms, age, sex and biomarkers of cance...
Source: Carcinogenesis - September 30, 2015 Category: Cancer & Oncology Authors: Espin-Perez, A., de Kok, T. M. C. M., Jennen, D. G. J., Hendrickx, D. M., De Coster, S., Schoeters, G., Baeyens, W., van Larebeke, N., Kleinjans, J. C. S. Tags: Original Manuscript Source Type: research
Differentially methylated microRNAs in prediagnostic samples of subjects who developed breast cancer in the European Prospective Investigation into Nutrition and Cancer (EPIC-Italy) cohort
The crosstalk between microRNAs (miRNAs) and other epigenetic factors may lead to novel hypotheses about carcinogenesis identifying new targets for research. Because a single miRNA can regulate multiple downstream target genes, its altered expression may potentially be a sensitive biomarker to detect early malignant transformation and improve diagnosis and prognosis. In the current study, we tested the hypothesis that altered methylation of miRNA encoding genes, associated with deregulated mature miRNA expression, may be related to dietary and lifestyle factors and may contribute to cancer development. In a case–cont...
Source: Carcinogenesis - September 30, 2015 Category: Cancer & Oncology Authors: Cordero, F., Ferrero, G., Polidoro, S., Fiorito, G., Campanella, G., Sacerdote, C., Mattiello, A., Masala, G., Agnoli, C., Frasca, G., Panico, S., Palli, D., Krogh, V., Tumino, R., Vineis, P., Naccarati, A. Tags: Original Manuscript Source Type: research
Association between indel polymorphism in the promoter region of lncRNA GAS5 and the risk of hepatocellular carcinoma
The growth arrest special 5 (GAS5) is known to be involved in various cancers. However, its expression regulation remains unclear. Polymorphisms in the promoter region of GAS5 may affect its expression and be associated with cancer susceptibility. In this research, we first evaluated the association of a 5-base pair indel polymorphism (rs145204276) in the promoter region of GAS5 with hepatocelluar carcinoma (HCC) susceptibility in Chinese populations. Logistic regression analysis showed that the deletion allele of rs145204276 significantly increased the risk of HCC in two independent case control sets (1034 HCC and 1054 co...
Source: Carcinogenesis - September 30, 2015 Category: Cancer & Oncology Authors: Tao, R., Hu, S., Wang, S., Zhou, X., Zhang, Q., Wang, C., Zhao, X., Zhou, W., Zhang, S., Li, C., Zhao, H., He, Y., Zhu, S., Xu, J., Jiang, Y., Li, L., Gao, Y. Tags: Original Manuscript Source Type: research
Gene-asbestos interaction in malignant pleural mesothelioma susceptibility
Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, on average less than 10% of subjects highly exposed to asbestos develop MPM, suggesting the possible involvement of other risk factors. To identify the genetic factors that may modulate the risk of MPM, we conducted a gene–environment interaction analysis including asbestos exposure and 15 single nucleotide polymorphisms (SNPs) previously identified through a genome-wide association study on Italian subjects. In the present study, we assessed gene–asbestos interaction on MPM risk using rela...
Source: Carcinogenesis - September 30, 2015 Category: Cancer & Oncology Authors: Tunesi, S., Ferrante, D., Mirabelli, D., Andorno, S., Betti, M., Fiorito, G., Guarrera, S., Casalone, E., Neri, M., Ugolini, D., Bonassi, S., Matullo, G., Dianzani, I., Magnani, C. Tags: Original Manuscript Source Type: research
Prediagnostic serum inflammatory markers in relation to breast cancer risk, severity at diagnosis and survival in breast cancer patients
Inflammation has been linked to cancer but its role in breast cancer is unclear. We investigated common serum markers of inflammation: C-reactive protein (CRP), albumin, haptoglobin and white blood cells (WBC) in relation to breast cancer incidence, severity and survival. A total of 155179 women aged 20 and older without any history of cancer were selected from a large Swedish cohort. Hazard ratios (HRs) for breast cancer were estimated with Cox regression, adjusting for potential confounders. Ordered and binomial logistic regression models were used to assess the associations of serum inflammatory markers with breast canc...
Source: Carcinogenesis - September 30, 2015 Category: Cancer & Oncology Authors: Wulaningsih, W., Holmberg, L., Garmo, H., Malmstrom, H., Lambe, M., Hammar, N., Walldius, G., Jungner, I., Van Hemelrijck, M. Tags: Original Manuscript Source Type: research
HBP21, a chaperone of heat shock protein 70, functions as a tumor suppressor in hepatocellular carcinoma
In this study, down-regulation of HBP21 was frequently detected in primary HCCs (87/120, 72.5%), which was significantly associated with advanced clinical stage (P = 0.049), poor differentiation (P = 0.018) and poor prognosis (P = 0.026). Further study found that down-regulation of HBP21 in HCC was mainly caused by allele loss and promoter methylation. Functional study found that HBP21 could inhibit tumor cell growth rate, foci formation and colony formation in soft agar, and tumor formation in nude mice when it was transfected into HCC cells. Molecular study found that HBP21 could promote cell apoptosis, especially under ...
Source: Carcinogenesis - September 30, 2015 Category: Cancer & Oncology Authors: Jiang, L., Kwong, D. L.-W., Li, Y., Liu, M., Yuan, Y.-F., Li, Y., Fu, L., Guan, X.-Y. Tags: Original Manuscript Source Type: research
