Ablation of osteopontin suppresses N-methyl-N-nitrosourea and Helicobacter pylori-induced gastric cancer development in mice
Several clinical studies have reported increased expression of osteopontin (OPN) in various types of human cancer, including gastric cancer. However, the precise mechanisms underlying tumor development remain unclear. In the present study, we investigated the pathogenic roles of OPN in Helicobacter pylori-induced gastric cancer development. Wild-type (WT) and OPN knockout (KO) mice were treated with N-methyl-N-nitrosourea (MNU) and infected with H.pylori. Mice were killed 50 weeks after treatment, and stomach tissues were assessed by histopathological examination, immunohistochemistry, quantitative real-time RT–PCR a...
Source: Carcinogenesis - November 28, 2015 Category: Cancer & Oncology Authors: Lee, S.-H., Park, J.-W., Go, D.-M., Kim, H. K., Kwon, H.-J., Han, S.-U., Kim, D.-Y. Tags: Original Manuscript Source Type: research

Connexin 32 and luteolin play protective roles in non-alcoholic steatohepatitis development and its related hepatocarcinogenesis in rats
In this study, we aimed to clarify the role of Cx32 and the chemopreventive effect of luteolin, an antioxidant flavonoid, on the progression of NASH and NASH-related hepatocarcinogenesis. Cx32 dominant negative transgenic (Cx32Tg) and wild-type (Wt) rats at 10 weeks of age were given diethylnitrosamine and fed methionine–choline-deficient diet (MCDD) or MCDD with luteolin for 12 weeks. MCDD induced steatohepatitis and fibrosis along with increased inflammatory cytokine expression and reactive oxygen species in the liver. These effects were more severe in Cx32Tg rats as compared with Wt rats, and significantly suppres...
Source: Carcinogenesis - November 28, 2015 Category: Cancer & Oncology Authors: Sagawa, H., Naiki-Ito, A., Kato, H., Naiki, T., Yamashita, Y., Suzuki, S., Sato, S., Shiomi, K., Kato, A., Kuno, T., Matsuo, Y., Kimura, M., Takeyama, H., Takahashi, S. Tags: Original Manuscript Source Type: research

Modulation by aspirin and naproxen of nucleotide alterations and tumors in the lung of mice exposed to environmental cigarette smoke since birth
Chemoprevention provides an important strategy for cancer control in passive smokers. Due to the crucial role played by smoke-related chronic inflammation in lung carcinogenesis, of special interest are extensively used pharmacological agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs). We evaluated the ability of aspirin and naproxen, inhibitors of both cyclooxygenase-1 and cyclooxygenase -2, to modulate environmental cigarette smoke (ECS)-induced lung carcinogenesis in A/J mice of both genders. Based on a subchronic toxicity study in 180 postweaning mice, we used 1600mg/kg diet aspirin and 320mg/kg diet naprox...
Source: Carcinogenesis - November 28, 2015 Category: Cancer & Oncology Authors: La Maestra, S., DAgostini, F., Izzotti, A., Micale, R. T., Mastracci, L., Camoirano, A., Balansky, R., Trosko, J. E., Steele, V. E., De Flora, S. Tags: Original Manuscript Source Type: research

Proinflammatory mesenchymal effects of the non-genotoxic hepatocarcinogen phenobarbital: a novel mechanism of antiapoptosis and tumor promotion
In conclusion, our findings reveal profound proinflammatory effects of PB on hepatic mesenchyme and mesenchymal–epithelial interactions. The resulting release of cytokines acts antiapoptotic in HC, an effect crucial for tumor promotion and carcinogenesis by NGC. (Source: Carcinogenesis)
Source: Carcinogenesis - November 28, 2015 Category: Cancer & Oncology Authors: Riegler, T., Nejabat, M., Eichner, J., Stiebellehner, M., Subosits, S., Bilban, M., Zell, A., Huber, W. W., Schulte-Hermann, R., Grasl-Kraupp, B. Tags: Original Manuscript Source Type: research

Diffuse-type gastric cancer cells switch their driver pathways from FGFR2 signaling to SDF1/CXCR4 axis in hypoxic tumor microenvironments
This study investigated the growth signaling of gastric cancer (GC) cells in focus on the interaction with CAFs and GC cells under normoxia and hypoxia. Four diffuse-type GC cell lines, two intestinal-type GC cell lines and three CAF cell lines were used. Cells were examined for expression of C-X-C chemokine receptor 4 (CXCR4), fibroblast growth factor receptor 2 (FGFR2) and stromal-derived factor 1 (SDF1) by RT-PCR, western blot, ELISA and immunohistochemical staining of xenografted tumors. GC cell proliferation was examined under hypoxia in the presence or absence of CAFs, a FGFR2 inhibitor, a CXCR4 inhibitor and HIF1&al...
Source: Carcinogenesis - November 28, 2015 Category: Cancer & Oncology Authors: Kinoshita, H., Yashiro, M., Fukuoka, T., Hasegawa, T., Morisaki, T., Kasashima, H., Masuda, G., Noda, S., Hirakawa, K. Tags: Original Manuscript Source Type: research

Mitochondrial DNA copy number in colorectal cancer: between tissue comparisons, clinicopathological characteristics and survival
This study further deciphers the role of mtDNA copy number in CRC by comparing mtDNA copy number between healthy, adenoma and carcinoma tissue, by investigating its association according to several clinicopathological characteristics in CRC, and by relating it to CRC-specific survival in CRC patients. A hospital-based series of samples including cancer, adenoma and adjacent histologically normal tissue from primary CRC patients (n = 56) and recurrent CRC (n = 16) was studied as well as colon mucosa samples from healthy subjects (n = 76). Furthermore, mtDNA copy number was assessed in carcinomas of 693 CRC cases identified ...
Source: Carcinogenesis - November 28, 2015 Category: Cancer & Oncology Authors: van Osch, F. H. M., Voets, A. M., Schouten, L. J., Gottschalk, R. W. H., Simons, C. C. J. M., van Engeland, M., Lentjes, M. H. F. M., van den Brandt, P. A., Smeets, H. J. M., Weijenberg, M. P. Tags: Original Manuscript Source Type: research

Gene-expression profiling of buccal epithelium among non-smoking women exposed to household air pollution from smoky coal
In China’s rural counties of Xuanwei and Fuyuan, lung cancer rates are among the highest in the world. While the elevated disease risk in this population has been linked to the usage of smoky (bituminous) coal as compared to smokeless (anthracite) coal, the underlying molecular changes associated with this exposure remains unclear. To understand the physiologic effects of smoky coal exposure, we analyzed the genome-wide gene-expression profiles in buccal epithelial cells collected from healthy, non-smoking female residents of Xuanwei and Fuyuan who burn smoky (n = 26) and smokeless (n = 9) coal. Gene-expression was p...
Source: Carcinogenesis - November 28, 2015 Category: Cancer & Oncology Authors: Wang, T. W., Vermeulen, R. C. H., Hu, W., Liu, G., Xiao, X., Alekseyev, Y., Xu, J., Reiss, B., Steiling, K., Downward, G. S., Silverman, D. T., Wei, F., Wu, G., Li, J., Lenburg, M. E., Rothman, N., Spira, A., Lan, Q. Tags: Original Manuscript Source Type: research

MicroRNA-218 is a prognostic indicator in colorectal cancer and enhances 5-fluorouracil-induced apoptosis by targeting BIRC5
In conclusion, we demonstrated that high miR-218 expression had a positive prognostic value in 5-FU-based treatments for CRC patients and discovered a novel mechanism mediated by miR-218 to promote apoptosis and to function synergistically with 5-FU to promote chemosensitivity by suppressing BIRC5 and TS in CRC. These suggest the unique potential of miR-218 as a novel candidate for developing miR-218-based therapeutic strategies in CRC. (Source: Carcinogenesis)
Source: Carcinogenesis - November 28, 2015 Category: Cancer & Oncology Authors: Li, P.-L., Zhang, X., Wang, L.-L., Du, L.-T., Yang, Y.-M., Li, J., Wang, C.-X. Tags: Original Manuscript Source Type: research

Serum angiopoietin-like protein 2 as a potential biomarker for diagnosis, early recurrence and prognosis in gastric cancer patients
Chronic inflammation of gastric mucosa by Helicobacter pylori infection can initiate gastric carcinogenesis. As angiopoietin-like protein 2 (ANGPTL2) mediates inflammation and inflammation-associated carcinogenesis, we investigated the functional and clinical significance of ANGPTL2 in human gastric cancer (GC). SiRNA knockdown studies were performed for the functional assessment of ANGPTL2 in GC cell lines. ANGPTL2 expression was evaluated immunohistochemically in 192 tissue specimens from GC patients. In addition, we screened serum ANGPTL2 levels from 32 GC patients and 23 healthy controls; and validated these results in...
Source: Carcinogenesis - November 28, 2015 Category: Cancer & Oncology Authors: Toiyama, Y., Tanaka, K., Kitajima, T., Shimura, T., Imaoka, H., Mori, K., Okigami, M., Yasuda, H., Okugawa, Y., Saigusa, S., Ohi, M., Inoue, Y., Mohri, Y., Goel, A., Kusunoki, M. Tags: Original Manuscript Source Type: research

miR-342-3p regulates MYC transcriptional activity via direct repression of E2F1 in human lung cancer
In this study, we attempted to identify miRNAs involved in regulation of MYC transcriptional activity in lung cancer. To this end, we utilized an integrative approach with combinatorial usage of miRNA and mRNA expression profile datasets of patient tumor tissues, as well as those of MYC-inducible cell lines in vitro. In addition to miRNAs previously reported to be directly regulated by MYC, including let-7 and miR-17–92, our strategy also helped to identify miR-342-3p as capable of indirectly regulating MYC activity via direct repression of E2F1, a MYC-cooperating molecule. Furthermore, miR-342-3p module activity, wh...
Source: Carcinogenesis - November 28, 2015 Category: Cancer & Oncology Authors: Tai, M. C., Kajino, T., Nakatochi, M., Arima, C., Shimada, Y., Suzuki, M., Miyoshi, H., Yatabe, Y., Yanagisawa, K., Takahashi, T. Tags: Original Manuscript Source Type: research

Aberrant DNA methylation in non-small cell lung cancer-associated fibroblasts
Epigenetic changes through altered DNA methylation have been implicated in critical aspects of tumor progression, and have been extensively studied in a variety of cancer types. In contrast, our current knowledge of the aberrant genomic DNA methylation in tumor-associated fibroblasts (TAFs) or other stromal cells that act as critical coconspirators of tumor progression is very scarce. To address this gap of knowledge, we conducted genome-wide DNA methylation profiling on lung TAFs and paired control fibroblasts (CFs) from non-small cell lung cancer patients using the HumanMethylation450 microarray. We found widespread DNA ...
Source: Carcinogenesis - November 28, 2015 Category: Cancer & Oncology Authors: Vizoso, M., Puig, M., Carmona, F. J., Maqueda, M., Velasquez, A., Gomez, A., Labernadie, A., Lugo, R., Gabasa, M., Rigat-Brugarolas, L. G., Trepat, X., Ramirez, J., Moran, S., Vidal, E., Reguart, N., Perera, A., Esteller, M., Alcaraz, J. Tags: Original Manuscript Source Type: research

Table_of_Contents
(Source: Carcinogenesis)
Source: Carcinogenesis - November 28, 2015 Category: Cancer & Oncology Tags: Cover / Standing Material Source Type: research

Subscriptions
(Source: Carcinogenesis)
Source: Carcinogenesis - November 28, 2015 Category: Cancer & Oncology Tags: Cover / Standing Material Source Type: research

Instructions_to_Authors
(Source: Carcinogenesis)
Source: Carcinogenesis - November 28, 2015 Category: Cancer & Oncology Tags: Cover / Standing Material Source Type: research

Front_Cover
(Source: Carcinogenesis)
Source: Carcinogenesis - November 28, 2015 Category: Cancer & Oncology Tags: Cover / Standing Material Source Type: research