MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Molecular Carcinogenesis' source. Thu, 09 Feb 2012 16:56:51 +0100 http://www.medworm.com/index.php?rid=5673927&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21881 AbstractPromoter hypermethylation is gaining strength as one of the main mechanisms through which tumor suppressor genes are silenced during tumor progression. Three tumor suppressor genes are frequently found methylated in their promoter, in concordance with absence of expression, RASSF1A, SLIT2, and WIF1. In addition, a previous array‐CGH analysis from our group showed that these genes are found in deleted genomic regions observed in hereditary breast cancer tumors. In the present work we analyzed the methylation status of these three tumor suppressor gene promoters in 47 hereditary breast cancer tumors. Promoter methylation status analysis of hereditary breast tumors revealed high methylation frequencies for the three genes (67% RASSF1A, 80% SLIT2, and 72% WIF1). Additionally, the pre... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5673927 Thu, 09 Feb 2012 21:17:58 +0100 5673927 http://www.medworm.com/index.php?rid=5673928&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21880 This study explores how the microRNA binding to the STR region affects ECRG2 expression in ESCC. Dual‐luciferase reporter assays were used to verify the effects of the four microRNAs (miR‐580, miR‐1182, miR‐1272, and miR‐1322) predicted to bind the STR region of the ECRG2 3′ untranslated region (UTR). The expression of identified effective microRNA was then analyzed in 44 paired ESCC and adjacent normal tissues and 402 case–controlled serum samples (divided into a discovery group and an independent validation group) by real‐time RT‐PCR assay. We found that only miR‐1322 could significantly down‐regulate the ECRG2 with TCA3 allele (P < 0.01), but it could not down‐regulate the ECRG2 with TCA4 allele significantly (P > 0.05). MiR‐1322 was also expresse... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5673928 Tue, 07 Feb 2012 05:00:00 +0100 5673928 http://www.medworm.com/index.php?rid=5664270&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21873 This study represents the first use of RNAseq to analyze tumors from animals consuming dietary phenethyl isothiocyanate and to identify potential molecular signatures that may explain the cancer protective effect of this compound. © 2012 Wiley Periodicals, Inc. (Source: Molecular Carcinogenesis) Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5664270 Mon, 06 Feb 2012 21:13:12 +0100 5664270 http://www.medworm.com/index.php?rid=5664271&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21879 This study examined the role of microRNAs (miRNAs) in mediating the chemo‐protective effects of HDIs, and explored functions of the oncogenic miR‐17‐92 cluster. The dysregulated miRNA expression observed in HT29 and HCT116 CRC cells could be epigenetically altered by butyrate, SAHA and TSA. These HDIs decreased expression of miR‐17‐92 cluster miRNAs (P < 0.05), with a corresponding increase in miR‐17‐92 target genes, including PTEN, BCL2L11, and CDKN1A (P < 0.05). The decrease in miR‐17‐92 expression may be partly responsible for the anti‐proliferative effects of HDIs, with introduction of miR‐17‐92 cluster miRNA mimics reversing this effect and decreasing levels of PTEN, BCL2L11, and CDKN1A (P < 0.05). The growth effects of HDIs may be mediated... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5664271 Sun, 05 Feb 2012 05:00:00 +0100 5664271 http://www.medworm.com/index.php?rid=5643835&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21878 AbstractThe prevalence of obesity, an established risk and progression factor for postmenopausal breast cancer, remains high in US women. Activation of Akt/mammalian target of rapamycin (mTOR) signaling plays a key role in the obesity–breast cancer link. However, the impact of weight normalization in obese postmenopausal women on breast tumorigenesis and/or Akt/mTOR activation is poorly characterized. To model this, ovariectomized female C57BL/6 mice were fed a control diet (n = 20), a calorie restriction (CR) regimen (n = 20), or a diet‐induced obesity (DIO) diet (n = 30). At week 17, DIO mice were switched to control diet, resulting in formerly obese (FOb) mice with weights identical to the controls by week 20. MMTV‐Wnt‐1 mammary tumor cells were injected at 20 wk i... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5643835 Tue, 31 Jan 2012 14:40:24 +0100 5643835 http://www.medworm.com/index.php?rid=5643838&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21875 AbstractBreast cancer patients with HER‐2 positive or estrogen receptor negative tumors have a poor prognosis because these tumors are aggressive and respond poorly to standard therapies. Histone deacetylase (HDAC) inhibitors have been shown to decreased cell survival, which suggests that HDAC inhibitors may be developed for preventing and treating breast cancer. Curcumin has anti‐inflammatory and proapoptotic effects in cancer cells. We determined whether the HDAC inhibitor, Tricostatin A (TSA) in combination with curcumin would produce greater antiproliferative and apoptotic effects than either agent alone. Increasing the concentration of curcumin from 10 to 20 µM enhanced the growth inhibitory effects of the combination in SkBr3 and 435eB breast cancer cells, which was accompanie... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5643838 Mon, 30 Jan 2012 05:00:00 +0100 5643838 http://www.medworm.com/index.php?rid=5643837&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21876 AbstractHepatocellular carcinoma (HCC) is a disease of multiple etiologies caused by the accumulation of genetic and epigenetic defects. Current evidence indicates that the transforming growth factor beta (TGF‐β) signaling pathway has a significant impact on different cellular process. Members of the TGF‐β superfamily (TGF‐β1, the type I TGF‐β receptor [TβRI], type II TGF‐β receptor [TβRII], and type III TGF‐β receptor]) play an important role in tumorigenesis. Numerous studies show that genetic polymorphisms in TGF‐β superfamily genes are associated with HCC in East Asian populations. We studied 16 single nucleotide polymorphisms (SNPs) in four genes (TGF‐β1, TβRI, TβRII, and TβRIII) to examine their associations with hepatocarcinogenesis. A total of 1228 Chin... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5643837 Mon, 30 Jan 2012 05:00:00 +0100 5643837 http://www.medworm.com/index.php?rid=5643836&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21877 This study clearly indicates that plumbagin can induce multiple pathways of apoptosis and cell cycle arrest in BRCA1 blocked cells compared to unblocked cells. © 2012 Wiley Periodicals, Inc. (Source: Molecular Carcinogenesis) Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5643836 Mon, 30 Jan 2012 05:00:00 +0100 5643836 http://www.medworm.com/index.php?rid=5593018&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21874 This study tested if serum MMP levels correlate with clinical features and predict survival for HNSCC, ESCC, and synchronous SCC. One hundred and thirty patients with SCCs in upper aero‐digestive tract (70 ESCC, 20 HNSCC, and 40 synchronous SCC) and 74 healthy controls were assessed for serum MMP‐3, ‐7, and ‐9 titers by enzyme‐linked immunosorbent assay. The titers were validated to their correlations to clinical features and survival rates of the different SCC groups. Patients with SCCs had significantly higher serum MMP‐3, ‐7, and ‐9 titers than the controls (P < 0.001) but there was no difference among the three SCC groups. Based on the optimal MMP cut‐off values by ROC curve, elevated MMP‐3 and MMP‐9, but not MMP‐7, correlated with distant metastasis and ... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5593018 Sun, 15 Jan 2012 10:40:26 +0100 5593018 http://www.medworm.com/index.php?rid=5568842&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21872 In this study, we genotyped the three SNPs in a case–control study with 1,033 cervical cancer cases and 1,053 cancer‐free controls in a Chinese population. Logistic regression analyses showed that the two TERT SNPs both significantly associated with cervical cancer risk in the recessive model (rs2736098, AA vs. AG/GG: adjusted OR = 1.35, 95% CI = 1.06–1.72; rs2736100, CC vs. AC/AA: adjusted OR = 1.38, 95% CI = 1.11–1.73). However, no association was found between CLPTM1L rs402710 and cervical cancer. These results suggest that genetic variants in 5p15.33, especially in TERT, may be markers for susceptibility to cervical cancer. © 2012 Wiley Periodicals, Inc. (Source: Molecular Carcinogenesis) Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5568842 Sat, 07 Jan 2012 03:40:29 +0100 5568842 http://www.medworm.com/index.php?rid=5568846&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21863 AbstractUsing relatively primitive tools in the 1920s, Otto Warburg demonstrated that tumor cells show an increased dependence on glycolysis to meet their energy needs, regardless of whether they were well‐oxygenated or not. High rates of glucose uptake, fueling glycolysis, are now used clinically to identify cancer cells. However, the Warburg effect does not account for the metabolic diversity that has been observed amongst cancer cells nor the influences that might direct such diversity. Modern tools have shown that the oncogenes, variable hypoxia levels, and the utilization of different carbon sources affect tumor evolution. These influences may produce metabolic symbiosis, in which lactate from a hypoxic, glycolytic tumor cell population fuels ATP production in the oxygenated region ... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5568846 Fri, 06 Jan 2012 05:00:00 +0100 5568846 http://www.medworm.com/index.php?rid=5568845&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21869 We examined whether the p73 G4C14‐to‐A4T14 polymorphism was related to the risk of developing lung cancer in a Chinese population. The p73 G4C14‐to‐A4T14 polymorphism was genotyped in 293 lung cancer patients and 380 cancer‐free controls of Han nationality in North China using PCR‐RFLP. Multivariate logistic regression analysis was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). We observed that compared with the GC/GC genotype, the genotypes containing AT allele (GC/AT + AT/AT genotypes) were associated with significantly increased susceptibility to lung cancer (OR, 1.48; 95% CI, 1.08–2.02; P = 0.014). In addition, compared with the GC/GC genotype, the GC/AT genotype was also significantly associated with increased susceptibility ... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5568845 Fri, 06 Jan 2012 05:00:00 +0100 5568845 http://www.medworm.com/index.php?rid=5568844&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21870 AbstractWe evaluated the effect of estrogen receptor (ER)‐α and ER‐β genes polymorphisms on development of prostate cancer (PCa) and its correlation with serum reproductive hormones and with clinicopathological characteristics in a sample of Iranian men. One hundred sixty‐two men with PCa (mean age 63.7 ± 13.4 years) and 324 age‐matched healthy controls (mean age 63.1 ± 13.2 years) were recruited in this study. Genotypes for ER‐α and ER‐β genes polymorphisms were identified by the polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) analysis. Serum levels of reproductive hormones were also measured. Of PCa patients, 38.3%, and 61.7% had localized and advanced tumor, and 45.7%, and 54.3%, had low grade and high‐grade cancer, respectiv... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5568844 Fri, 06 Jan 2012 05:00:00 +0100 5568844 http://www.medworm.com/index.php?rid=5568843&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21871 In this study, we conducted a genotyping analysis for EZH2 in 311 cases of gastric cancer and 425 controls from the Chinese Han population. We found five single nucleotide polymorphisms (SNP; rs12670401, rs6464926, rs2072407, rs734005, and rs734004) of EZH2 gene were significantly associated with the risk of gastric cancer. Of which, the rs12670401 with the minor allele C and rs6464926 with the minor allele T revealed strong associations with increased gastric cancer risk [P = 0.009, adjusted odds ratio (aOR) = 1.327, 95% CI = 1.075–1.683 and P = 0.012, aOR = 1.310, 95% CI = 1.059–1.619]. The other three SNPs, rs2072407, rs734005, and rs734004 contributed to significantly reduced risk of gastric cancer (P = 0.033, aOR = 0.787, 95% CI = 0.633–0.981,... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5568843 Fri, 06 Jan 2012 05:00:00 +0100 5568843 http://www.medworm.com/index.php?rid=5549779&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21868 AbstractPolymorphisms in metabolic and DNA repair genes may alter protein function, consequently affecting patients' response to chemo/radiotherapy. We retrospectively assessed whether polymorphisms of glutathione‐S‐transferase genes GSTM1 (deletion), GSTT1 (deletion), GSTP1 (Ile105Val, rs1695), and DNA repair genes hOGG1 (Ser326Cys, rs1052133), XRCC1 (Arg194Trp, rs1799782, and Arg399Gln, rs25487), XPD (Asp312Asn, rs1799793, and Lys751Gln, rs13181) can predict clinical outcome in 187 oral squamous cell carcinoma patients treated with postoperative radiotherapy. The Cox proportional hazards model was used to evaluate the role of polymorphic genotypes on relapse‐free (RFS) and disease‐specific (DSS) survival. Deletion polymorphism of GSTM1 gene was significantly associated with DSS. ... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5549779 Thu, 29 Dec 2011 15:04:13 +0100 5549779 http://www.medworm.com/index.php?rid=5549783&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21858 AbstractThe present study was performed to investigate the critical role of 5‐lipoxygenase (5‐LOX) in 7,12‐dimethylbenz(α)anthracene (DMBA)‐induced rat mammary inflammation associated carcinogenesis. Female Sprague–Dawley rats at 50 days of age were treated with 7,12‐dimethylbenz(α)anthracene (DMBA; 0.5 mg/100 g body weight) by a single tail vein injection, followed by administration of zileuton (2000 mg/kg diet) from week 7 until the termination of the study at 31 wk. 5‐LOX protein expression, 5‐hydroxyeicosatetraenoic acid (5‐HETE), and leukotriene B4 (LTB4) production in rat mammary tissue were analyzed at 6, 12, and 24 wk post‐DMBA injection. Rate of cell proliferation was analyzed by bromodioxyuridine labeling index (BrdU‐LI). Microvessel density, lev... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5549783 Wed, 28 Dec 2011 05:00:00 +0100 5549783 http://www.medworm.com/index.php?rid=5549782&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21866 The objective of this investigation was to examine the anti‐cancer activity of TA using established human neuroblastoma cell lines. We tested the anti‐proliferative effect of TA using SH‐SY5Y, CHLA90, LA1 55n, SHEP, Be2c, CMP 13Y, and SMS KCNR cell lines. Cells were treated with TA (0/25/50/100 µM) and cell viability was measured at 24, 48, and 72 h post‐treatment. Selected neuroblastoma cell lines were treated with 50 µM TA for 24 and 48 h and tested for cell apoptosis using Annexin‐V staining. Caspase activity was measured with caspase 3/7 Glo kit. Cell lysates were prepared and the expression of Sp1, survivin, and c‐PARP were evaluated through Western blot analysis. TA significantly inhibited the growth of neuroblastoma cells in a dose/time‐dependent manner and s... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5549782 Wed, 28 Dec 2011 05:00:00 +0100 5549782 http://www.medworm.com/index.php?rid=5549781&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21859 AbstractDue to the lack of effective diagnostic tools, most patients with cholangiocarcinoma (CCA) have no chance of surgical resection. Ars2 is a protein that was reported to be important for microRNA (miR) biogenesis, and its depletion can reduce the levels of several miRs, including miR‐21, which is overexpressed in CCAs. We hypothesized that Ars2 was also present in CCAs and could be an early diagnostic marker. In our experiments, Ars2, PTEN, PDCD4, and miR‐21 were evaluated in 18 CCAs and paired normal tissues. ShArs2, miR‐21 mimics, and Ars2 were transfected into CCA and bile duct epithelial cells either alone or together. Cell proliferation, tumorigenicity analysis and expression changes of Ars2, PTEN, PDCD4, and miR‐21 were evaluated. We found that both Ars2 and miR‐21 we... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5549781 Wed, 28 Dec 2011 05:00:00 +0100 5549781 http://www.medworm.com/index.php?rid=5549780&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21867 AbstractPolycyclic aromatic molecules such as ellipticine intercalate into double‐stranded DNA and interfere with physiological functions. In the present study, we evaluate the chemotherapeutic potential of MPTQ on animal models and its mode of action. In order to test the antitumor activity, monohydrochloride of MPTQ was orally administered in mice bearing tumor. Results showed a significant inhibition of tumor growth compared to that of untreated controls. More importantly, mean lifespan of tumor bearing animals treated with MPTQ was significantly higher as compared to that of untreated tumor bearing mice suggesting that the treatment affected viability of cancerous cells, but not of normal cells. Consistent with this, we find that administration of MPTQ to normal mice did not cause an... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5549780 Wed, 28 Dec 2011 05:00:00 +0100 5549780 http://www.medworm.com/index.php?rid=5549793&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21854 In this study, immunohistochemistry was performed to examine expressive levels of δ‐catenin, cdc42, and Rac1 in 135 cases of nonsmall cell lung cancer (NSCLC), including 60 cases with follow‐up records. Thirty samples of paired lung cancer tissues and adjacent normal lung tissues were collected to analyze mRNA and protein expression of δ‐catenin and small GTPases. The effects of δ‐catenin on small GTPases expression and invasive ability of lung cancer cells were also evaluated. Compared with normal lung tissues, both mRNA and protein levels of δ‐catenin and small GTPases were increased in lung cancer tissues (P < 0.05), and the expression of small GTPases directly correlated with that of δ‐catenin (P < 0.001). In addition, δ‐catenin and small GTPases tende... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5549793 Tue, 27 Dec 2011 05:00:00 +0100 5549793 http://www.medworm.com/index.php?rid=5549792&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21857 AbstractNasopharyngeal carcinoma (NPC) is a multifactorial and polygenic disease with high incidence in Asian countries. Epstein–Barr virus infection, environmental and genetic factors are believed to be involved in the tumorigenesis of NPC. The association of single nucleotide polymorphisms (SNPs) in LPLUNC1 and SPLUNC1 genes with NPC was investigated by performing a two‐stage case control association study in a Malaysian Chinese population. The initial screening consisted of 81 NPC patients and 147 healthy controls while the replication study consisted of 366 NPC patients and 340 healthy controls. The combined analysis showed that a SNP (rs2752903) of SPLUNC1 was significantly associated with the risk of NPC (combined P = 0.00032, odds ratio = 1.62, 95% confidence interval ... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5549792 Tue, 27 Dec 2011 05:00:00 +0100 5549792 http://www.medworm.com/index.php?rid=5549791&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21856 AbstractWe previously reported that ductal infiltrating carcinomas (d.i.c.) of the human breast display profound modifications of the stromal architecture, associated with anomalous collagen composition. Among the major alterations observed in the interstitial collagen, the relative increase of type V collagen content was detected. When type V collagen was used as an “in vitro” substrate for 8701‐BC d.i.c. cells, it appeared able to restrain cell growth, inhibit cell motility and invasion “in vitro”, and modify the expression levels of genes coding for apoptosis factors, caspases and stress response proteins. In the present paper we demonstrate that type V collagen induces the down‐regulation of protein kinase C η, an event that may be, at least in part, responsible of the pre... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5549791 Tue, 27 Dec 2011 05:00:00 +0100 5549791 http://www.medworm.com/index.php?rid=5549790&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21855 AbstractThe prevalence of hepatocellular carcinoma (HCC) was diminished from 60% to 18% at 15 months of age in C3HeB/FeJ male transgenic mice expressing hMGMT in our previous studies. To directly test if the methyltransferase activity is required for diminished tumor prevalence, two separate lines of transgenic mice bearing an enzymatically inactive form of hMGMT were used. In these lines, cysteine 145 was substituted with alanine (C145A). Expression of the hMGMT C145A transgene in liver was demonstrated by Northern blots and Western blots. Immunohistochemistry revealed predominantly nuclear localization of the hMGMT C145A protein. hMGMT C145A transgenic mice were crossed with lacI transgenic mice to assess mutant frequencies in the presence of the mutant protein. Mutant frequencies were s... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5549790 Tue, 27 Dec 2011 05:00:00 +0100 5549790 http://www.medworm.com/index.php?rid=5549789&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21864 AbstractMicroRNAs are a class of non‐coding molecules found to regulate a variety of cellular functions in health and disease. Dysregulation of microRNAs is involved in liver disease, especially hepatocarcinogenesis. Since primary hepatic malignancies are typically characterized by late diagnosis, frequent recurrence, and poor response to adjuvant therapy, there is a need for the discovery of novel biomarkers in order to achieve earlier diagnosis, predict tumor aggressiveness and response to adjuvant therapy. The purpose of this study is to evaluate the expression of certain microRNAs (miR‐21, ‐31, ‐122, ‐145, ‐146a, ‐ 200c, ‐221, ‐222 and ‐223) in patients with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), as well as to assess their prognost... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5549789 Tue, 27 Dec 2011 05:00:00 +0100 5549789 http://www.medworm.com/index.php?rid=5549788&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21862 In conclusion, the current data suggested that XPC Lys939Gln and XPG Asp1104His polymorphisms might contribute to the identification of patients with increased risk for CRC. © 2011 Wiley Periodicals, Inc. (Source: Molecular Carcinogenesis) Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5549788 Tue, 27 Dec 2011 05:00:00 +0100 5549788 http://www.medworm.com/index.php?rid=5549787&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21861 AbstractCarcinogenesis is a multistep sequential process of clonal expansion of initiated cells associated with the accumulation of multiple cancer‐specific heritable phenotypes. The acquisition of these heritable cancer‐specific alterations may be triggered by mutational and/or non‐mutational changes in the genome that affect the regulation of gene expression. Currently, cancer‐specific epigenetically mediated changes in gene expression are regarded as driving events in tumorigenesis. In the present study, we investigated the role of gene‐specific expression changes in the mechanism of rat hepatocarcinogenesis induced by the complete hepatocarcinogen 2‐acetylaminofluorene (2‐AAF). The results of the present study demonstrate significant alterations in gene expression, especi... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5549787 Tue, 27 Dec 2011 05:00:00 +0100 5549787 http://www.medworm.com/index.php?rid=5549786&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21860 AbstractBlack currant fruits containing high amounts of anthocyanins are known to possess potent antioxidant and anti‐inflammatory properties. We have previously reported that anthocyanin‐rich black currant skin extract (BCSE) inhibits diethylnitrosamine (DENA)‐initiated hepatocarcinogenesis in rats although the underlying mechanisms are not fully understood. Our present study investigates the anti‐inflammatory mechanisms of BCSE during DENA rat liver carcinogenesis. Dietary BCSE (100 or 500 mg/kg) treatment for 22 wk afforded a striking inhibition of DENA‐induced hepatic gamma‐glutamyl transpeptidase‐positive preneoplastic foci in a dose‐responsive fashion. There was a significant increase in hepatic expression of heat shock proteins (HSP70 and HSP90), cyclooxygenase�... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5549786 Tue, 27 Dec 2011 05:00:00 +0100 5549786 http://www.medworm.com/index.php?rid=5549785&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21865 This study aims at investigating if CD25 variability affects breast carcinogenesis. Two polymorphisms (rs7072793 C > T, rs3118470 C > T) in the promoter of CD25 were selected and analyzed by a multiple independent case‐control study to assess the association between CD25 genotypes and breast cancer risk. Genotyping a total of 1110 patients and 1060 healthy controls in Chinese populations showed that rs7072793 CT genotype had an odd ratio of 1.49 (95% confidence interval, 1.23–1.89) for developing breast cancer compared with CC genotype, the rs7072793 TT carriers had a further increased risk of breast cancer (OR = 2.11; 95% CI = 1.66–2.87). Furthermore, our transient transfection which focused on reporter gene expression modulated by CD25 promoter demonstrated th... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5549785 Tue, 27 Dec 2011 05:00:00 +0100 5549785 http://www.medworm.com/index.php?rid=5549784&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21853 AbstractThe WW domain‐containing oxidoreductase (WWOX) gene, located on chromosome 16q23.3–24.1 in the region recognized as the common fragile site FRA16D is considered to be a tumor suppressor gene involved in various carcinomas. The present study was to investigate the alterations of WWOX expression and its correlation with polymorphism, the level of WWOX loss of heterozygosity (LOH), and methylation status in esophageal squamous cell carcinoma (ESCC). Immunohistochemistry and RT‐PCR methods were used, respectively, to examine the protein and mRNA expression of WWOX in ESCC tissues. PCR‐RFLP, PCR‐SSLP, and MSP approach were used, respectively, to detect polymorphisms of rs3764340, rs2548861, and rs1079635 site, the level of LOH, and WWOX methylation status. Family history of up... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5549784 Tue, 27 Dec 2011 05:00:00 +0100 5549784 http://www.medworm.com/index.php?rid=5501095&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20794 ConclusionConsuming well‐done meat cooked at high temperatures, which contains high mutagen levels, appears to confer increased risk of pancreatic cancer. © 2011 Wiley Periodicals, Inc. (Source: Molecular Carcinogenesis) Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5501095 Wed, 14 Dec 2011 11:13:20 +0100 5501095 http://www.medworm.com/index.php?rid=5501094&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20833 This article reviews the current epidemiological and experimental evidence investigating the relationship of dietary fat, vitamin D, and folate with pancreatic cancer. Additionally the mechanisms by which these risk factors may contribute to cancer, the methodological challenges involved with assessing risk, and other obstacles encountered when ascertaining the magnitude and direction of these three exposures are discussed. Published 2011. This article is a U.S. Government work and is in the public domain in the USA. (Source: Molecular Carcinogenesis) Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5501094 Wed, 14 Dec 2011 11:13:19 +0100 5501094 http://www.medworm.com/index.php?rid=5501093&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20826 AbstractThirty years of research with animal models has shown that pancreatic adenocarcinoma is induced by N‐nitrosamine carcinogens, which damage DNA through adduct formation. Human risk factors for pancreatic cancer include gastric colonization by Helicobacter pylori, as well as dietary intake of those same N‐nitrosamines or of nitrite which forms those N‐nitrosamines in the stomach, and cigarette smoking which also contains those N‐nitrosamines. Physiologic actions of H. pylori colonization enhance the carcinogenic effect of N‐nitrosamines delivered by smoking or dietary sources. This effect is modulated by host inflammatory response to the organism, by various virulence and other properties of the Helicobacter itself, and by host‐organism interactions. A recent genome‐wid... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5501093 Wed, 14 Dec 2011 11:13:18 +0100 5501093 http://www.medworm.com/index.php?rid=5501092&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20779 The objective of this review article is to report on the more recently published studies (1998–2010), and provide a summary of the most consistently reported occupational risk factors for pancreatic cancer, including exposure to chlorinated hydrocarbon compounds, pesticides, polycyclic aromatic hydrocarbons (PAHs), metals, nitrosamines, radiation, various airborne particles, and employment in sedentary occupations. We conclude that the strongest and most consistent findings linking occupational exposures with pancreatic cancer risk to date are for chlorinated hydrocarbons and PAHs. © 2011 Wiley Periodicals, Inc. (Source: Molecular Carcinogenesis) Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5501092 Wed, 14 Dec 2011 11:13:17 +0100 5501092 http://www.medworm.com/index.php?rid=5501091&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20816 AbstractWe review the current evidence for associations of several medical conditions with risk of pancreatic cancer, including allergies, pancreatitis, gall bladder disease, cholecystectomy, ulcers, gastrectomy, appendectomy, and tonsillectomy. There are consistent findings of reduced risk associated with presence of self‐reported allergies, particularly hay fever but not asthma; data on other allergies are limited and inconclusive. Several studies provide evidence that patients with pancreatic cancer are more likely than comparison groups to report pancreatitis. Those studies that investigated the time between onset of pancreatitis and diagnosis of pancreatic cancer found that risk estimates declined with longer periods of time; however, increased risks were noted for long‐term pancr... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5501091 Wed, 14 Dec 2011 11:13:15 +0100 5501091 http://www.medworm.com/index.php?rid=5501090&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20771 AbstractType 2 diabetes mellitus is likely the third modifiable risk factor for pancreatic cancer after cigarette smoking and obesity. Epidemiological investigations have found that long‐term type 2 diabetes mellitus is associated with a 1.5‐fold to 2.0‐fold increase in the risk of pancreatic cancer. A causal relationship between diabetes and pancreatic cancer is also supported by findings from prediagnostic evaluations of glucose and insulin levels in prospective studies. Insulin resistance and associated hyperglycemia, hyperinsulinemia, and inflammation have been suggested to be the underlying mechanisms contributing to development of diabetes‐associated pancreatic cancer. Signaling pathways that regulate the metabolic process also play important roles in cell proliferation and t... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5501090 Wed, 14 Dec 2011 11:13:14 +0100 5501090 http://www.medworm.com/index.php?rid=5501089&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20778 AbstractIn the United States, pancreatic cancer is characterized by a low 5‐yr survival rate of approximately 6%, fewer than 10% of patients diagnosed with localized disease and thus candidates for “curative” surgical resection, increasing incidence and few established risk factors. Similar statistics are observed for other industrialized nations. With new evidence to suggest that pancreatic cancer develops over a number of years, markers that can better identify high risk patients and are applicable to earlier diagnosis hold promise for improving these dire statistics. Obesity is one of the few modifiable risk factors that has been associated with increased risk of pancreatic cancer and also is related to increased risk of diabetes, a condition that in turn has been associated with ... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5501089 Wed, 14 Dec 2011 11:13:13 +0100 5501089 http://www.medworm.com/index.php?rid=5501088&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20786 AbstractTobacco smoking represents an important known cause of ductal pancreatic adenocarcinoma. Recent data from pooled analyses in consortia involving multiple case–control and cohort studies suggest that heavy (but not moderate or light) alcohol consumption also may increase pancreatic cancer risk. Animal and human evidence indicate that tobacco carcinogens and metabolites may act in concert and have both genetic and epigenetic effects at early and later stages in pancreatic tumorigenesis. One of the more important tobacco‐related carcinogens, NNK, probably acts via multiple pathways. Heavy alcohol consumption may increase pancreatic cancer risk by potentiating the effects of other risk factors such as tobacco smoking, poor nutrition, and inflammatory pathways related to chronic pan... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5501088 Wed, 14 Dec 2011 11:13:12 +0100 5501088 http://www.medworm.com/index.php?rid=5501087&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20827 This article highlights some of the most common pathway aberrations involved with this disease, and how these may subsequently affect one or both cellular compartments. Consequently, furthering our understanding of these pathways in terms of their function on the tumoral epithelial and stromal compartments may prove to be crucial to the development of targeted and more successful therapies in the future. © 2011 Wiley Periodicals, Inc. (Source: Molecular Carcinogenesis) Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5501087 Wed, 14 Dec 2011 11:13:11 +0100 5501087 http://www.medworm.com/index.php?rid=5501086&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20855 AbstractPancreatic cancer is the fourth leading cause of cancer death in both men and women in the United States. However, it has the poorest prognosis of any major tumor type, with a 5‐yr survival rate of approximately 5%. Cigarette smoking, increased body mass index, heavy alcohol consumption, and a diagnosis of diabetes mellitus have all been demonstrated to increase risk of pancreatic cancer. A family history of pancreatic cancer has also been associated with increased risk suggesting inherited genetic factors also play an important role, with approximately 5–10% of pancreatic cancer patients reporting family history of pancreatic cancer. While the genetic basis for the majority of the familial clustering of pancreatic cancer remains unclear, several important pancreatic cancer gen... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5501086 Wed, 14 Dec 2011 11:13:10 +0100 5501086 http://www.medworm.com/index.php?rid=5501085&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20785 AbstractPancreatic cancer mortality rates have been increasing in high‐income countries between the 1950s and the 1980s, and have leveled off or declined thereafter, particularly in men. To provide a global overview of recent pancreatic cancer mortality, we analyzed official death of the world certification data derived from the World Health Organization for 35 European countries and 19 other countries over the period 1980–2007. In 2007, the highest mortality rates from pancreatic cancer were in the Baltic countries, and some central/eastern and northern European countries (over 9.5/100 000 men and 6/100 000 women), whereas the lowest ones were in Latin America and Hong Kong (below 5/100 000 men and 3/100 000 women). Japan, the USA, Russia and the European Union (EU), as well a... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5501085 Wed, 14 Dec 2011 11:13:09 +0100 5501085 http://www.medworm.com/index.php?rid=5501084&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20876 (Source: Molecular Carcinogenesis) Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5501084 Wed, 14 Dec 2011 11:13:07 +0100 5501084 http://www.medworm.com/index.php?rid=5483091&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21844 We present a summary of the various formats used in the field of tissue bioengineering as they apply to mechanistic modeling of cancer stages or processes. In addition we list studies that model specific types of malignancies, highlight drastic differences in results between 3D in vitro models and classical monolayer culturing techniques, and establish the need for standardization of 3D models for meaningful preclinical and therapeutic testing. © 2011 Wiley Periodicals, Inc. (Source: Molecular Carcinogenesis) Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5483091 Wed, 07 Dec 2011 05:00:00 +0100 5483091 http://www.medworm.com/index.php?rid=5483090&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21848 In this study, we first confirmed that the over‐expression of EZH2 is a frequent event in oral tongue squamous cell carcinoma (OTSCC). We further demonstrated that EZH2 over‐expression is correlated with advanced stages of the disease and is associated with lymph node metastasis. Statistical analysis revealed that EZH2 over‐expression was correlated with reduced overall survival. Furthermore, over‐expression of EZH2 was correlated with reduced expression of tumor suppressor gene E‐cadherin. These observations were confirmed in vitro, in which knockdown of EZH2‐induced E‐cadherin expression and reduced cell migration and invasion. In contrast, ectopic transfection of EZH2 led to reduced E‐cadherin expression and enhanced cell migration and invasion. Furthermore, EZH2 may act... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5483090 Wed, 07 Dec 2011 05:00:00 +0100 5483090 http://www.medworm.com/index.php?rid=5483089&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21849 AbstractMicroRNAs (miRNAs) are small, 18‐ to 22‐nucleotide non‐coding RNAs that regulate target gene expression. Although recent studies focused on various diseases that harbor the miR‐146aC>G (rs2910164), 149C>T (rs2292832), 196a2C>T (rs11614913), and 499A>G (rs3746444) polymorphisms, the role of miRNA genetic variants in colorectal cancer is still unknown. The present study aimed to evaluate the role of four miRNA polymorphisms in patients with colorectal cancer. We enrolled 446 colorectal cancer patients and 502 control subjects from the Korean population. We found a significantly increased colorectal cancer risk with the miR‐196a2CC genotype compared with the TT/CT genotype (AOR = 1.50; 95% CI = 1.11–2.04; P = 0.01; FDR‐P = 0.04). In the strati... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5483089 Wed, 07 Dec 2011 05:00:00 +0100 5483089 http://www.medworm.com/index.php?rid=5483088&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21850 In conclusion, Cx43 and gemcitabine combined with HSV‐TK/GCV gene therapy using nonviral vector G5‐PAMAM‐D hold great potential as a novel approach for the gene therapy of prostate cancer. © 2011 Wiley Periodicals, Inc. (Source: Molecular Carcinogenesis) Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5483088 Wed, 07 Dec 2011 05:00:00 +0100 5483088 http://www.medworm.com/index.php?rid=5483087&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21852 In conclusion, we have identified overexpression of Evi‐1 oncoprotein as a novel mechanism by which a subset of human CRCs may escape TGF‐β regulation. We have also identified a novel Evi‐1 transcript, Evi‐1e, as the major Evi‐1 transcript expressed in human CRCs. © 2011 Wiley Periodicals, Inc. (Source: Molecular Carcinogenesis) Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5483087 Wed, 07 Dec 2011 05:00:00 +0100 5483087 http://www.medworm.com/index.php?rid=5483086&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21851 In this study, to assess the biological role of LPA receptor‐3 (LPA3) in the pathogenesis of tumor cells, we generated the Lpar3‐expressing cells (RHa3B12 and RHa3G8) from rat hepatoma RH7777 cells, and examined their abilities of cell migration and tumorigenicity, compared with the Lpar3‐unexpressing cells. In cell motility and invasion assays, RHa3B12 and RHa3G8 cells showed significantly higher intrinsic activity without LPA treatment than control RH7777AB cells. LPA treatment further increased cell motility and invasion of these cells. The cell motility of RHa3B12 and RHa3G8 cells stimulated by LPA treatment was significantly suppressed by pretreatment with inhibitors of Gi or Gq proteins. In a soft agar assay, the large sized colonies were formed in RHa3B12 and RHa3G8 cells, but... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5483086 Wed, 07 Dec 2011 05:00:00 +0100 5483086 http://www.medworm.com/index.php?rid=5483085&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21845 In this study we measured the expression levels of candidate FZD7 ligands, Wnt3 and Wnt11 in colon cancer cell lines (n = 7) and primary CRC tissues (n = 133) by quantitative RT‐PCR. We also examined the functional effects of Wnt11 with the use of Wnt11 transfectants of colon cancer HCT‐116 cells. Wnt11 transfectants showed the increased proliferation and migration/invasion activities compared to mock cells. Western blot analysis of transfectants revealed that phosphorylation of JNK and c‐jun was increased after Wnt11 transfection. Wnt11 mRNA expression was significantly higher in the stage I, II, III, or IV tumor tissues than in non‐tumor tissues (overall P < 0.003), while there was no significant difference in Wnt3 mRNA expression between tumor and non‐tumor tiss... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5483085 Thu, 01 Dec 2011 05:00:00 +0100 5483085 http://www.medworm.com/index.php?rid=5454062&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21832 AbstractColorectal carcinoma is a frequent cause of cancer‐related death in the world for men and women. microRNAs are endogenous small noncoding RNAs that regulate gene expression negatively at post‐transcriptional level. Here, we investigated the possible role of microRNAs in the development of multidrug resistance (MDR) in colorectal carcinoma cells. We analyzed microRNA (miRNA) expression levels between multidrug resistant colorectal carcinoma cell line HCT116/L‐OHP and its parent cell line HCT116 using a miRNA microarray. miR‐1915 had the lowest expression of miRNA in HCT116/L‐OHP cells compared to its parental cells. Overexpression of Bcl‐2 is generally associated with tumor drug resistance, meanwhile Bcl‐2 is a predicted target of miR‐1915. We found that elevated lev... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5454062 Tue, 29 Nov 2011 10:18:04 +0100 5454062 http://www.medworm.com/index.php?rid=5454067&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21847 (Source: Molecular Carcinogenesis) Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5454067 Mon, 28 Nov 2011 05:00:00 +0100 5454067 http://www.medworm.com/index.php?rid=5454066&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21846 In this study, we identify a potentially adverse effect of HDACIs through induction of both 15‐PGDH and COX‐2 leading to elevated PGE2 levels and thereby stimulation of angiogenesis. Co‐treatment of TSA and INN shows more potent anti‐angiogenic effects by inducing 15‐PGDH and inhibiting COX‐2. Overall, our results suggest that combined HDACI and COX inhibition should be explored clinically to achieve more meaningful benefits from HDACI therapy in lung cancer. © 2011 Wiley Periodicals, Inc. (Source: Molecular Carcinogenesis) Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5454066 Mon, 28 Nov 2011 05:00:00 +0100 5454066 http://www.medworm.com/index.php?rid=5454065&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21840 This study aimed to elucidate mechanisms underpinning the association of obesity and cancer, and to determine if visceral obesity is associated with aggressive tumour biology in OAC. Following co‐culture with visceral adipose tissue explants, expression of genes involved in tumour cell invasion and metastasis (matrix metalloproteinase (MMP)2 and MMP9) were upregulated between 10‐fold (MMP2) and 5000‐fold (MMP9), and expression of tumour suppressor p53 was downregulated 2‐fold in OAC cell lines. Western blotting confirmed these results at the protein level, while zymographic analysis detected increased activity of MMPs in OAC cell lines following co‐culture with adipose tissue explants. When OAC cell lines were cultured with adipose tissue conditioned media (ACM) from visceral adi... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5454065 Mon, 28 Nov 2011 05:00:00 +0100 5454065 http://www.medworm.com/index.php?rid=5454064&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21841 AbstractThe Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway is involved in immune function and cell growth. We evaluated the association between genetic variation in JAK1 (10 SNPs), JAK2 (9 SNPs), TYK2 (5 SNPs), suppressors of cytokine signaling (SOCS)1 (2 SNPs), SOCS2 (2 SNPs), STAT1 (16 SNPs), STAT2 (2 SNPs), STAT3 (6 SNPs), STAT4 (21 SNPs), STAT5A (2 SNPs), STAT5B (3 SNPs), STAT6 (4 SNPs) with risk of colorectal cancer. We used data from population‐based case‐control studies (colon cancer n = 1555 cases, 1,956 controls; rectal cancer n = 754 cases, 959 controls). JAK2, SOCS2, STAT1, STAT3, STAT5A, STAT5B, and STAT6 were associated with colon cancer; STAT3, STAT4, STAT6, and TYK2 were associated with rectal cancer. Given the biolog... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5454064 Mon, 28 Nov 2011 05:00:00 +0100 5454064 http://www.medworm.com/index.php?rid=5454063&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21837 AbstractSingle nucleotide polymorphisms (SNPs) of matrix metalloproteinase3 (MMP3) promoter in the development and progression of gastric cancer of whole stomach has never been investigated in any population. We conducted a hospital‐based case‐control study to explore the MMP3 SNPs and their haplotypes with the risk of gastric cancer for the first time in eastern Indian population. A total of 218 gastric cancer patients and 175 healthy controls were genotyped for MMP3‐1612 5A/6A (rs3025058) by PCR–RFLP and rechecked 10% by DNA sequencing. MMP3‐707 A/G (rs522616) and MMP3‐375 C/G (rs617819) were genotyped by DNA sequencing among 209 patients and 154 controls. MMP3‐1612 5A6A genotype (P = 0.026, odds ratio (OR) = 1.756, confidence interval (CI) = 1.070–2.883), c... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5454063 Mon, 28 Nov 2011 05:00:00 +0100 5454063 http://www.medworm.com/index.php?rid=5417606&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20878 In this study, we investigated the cellular and molecular function of JHDM1B in AML cells. In AML cell lines and AML‐derived ALDHhi (high aldehyde dehydrogenase activity)/CD34+ cells, the levels of JHDM1B mRNA were significantly higher than in normal ALDHhi/CD34+ cells. Reduction of JHDM1B expression in AML cells inhibited cell proliferation compared to control cells, through induction of G1 cell cycle arrest, an increase in the p15Ink4b mRNA and protein expression. JHDM1B mRNA was overexpressed in all 133 AML clinical specimens tested (n = 22, 57, 34, and 20 for M1, 2, 4, and 5 subtypes respectively). Compared to normal ALDHhi/CD34+ cells, JHDM1B gene expression was 1.57‐ to 1.87‐fold higher in AML‐derived ALDHhi/CD34+cells. Moreover, the JHDM1B protein was more strongly expre... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5417606 Fri, 18 Nov 2011 00:25:32 +0100 5417606 http://www.medworm.com/index.php?rid=5417617&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21833 AbstractUDP‐glucuronosyltransferases (UGTs), major phase II drug metabolism enzymes, play an important role in urinary bladder cancer initiation by detoxifying carcinogens. We aimed to determine if androgens regulate UGT expression via the androgen receptor (AR) pathway in the bladder. Real‐time reverse transcription‐polymerase chain reaction and Western blot analyses were used to assess UGT1A levels in the normal urothelium SVHUC cell line stably expressed with AR and in bladder tissues from AR knockout (ARKO) and castrated male mice. Immunohistochemistry was also performed in radical cystectomy specimens. Dihydrotestosterone (DHT) treatment in SVHUC‐AR reduced mRNA expression of all the UGT1A subtypes (19–75% decrease), and hydroxyflutamide antagonized the DHT effects. In contr... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5417617 Tue, 15 Nov 2011 05:00:00 +0100 5417617 http://www.medworm.com/index.php?rid=5417616&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21836 AbstractAnaplastic lymphoma kinase (ALK) has emerged as an important oncogene in a number of human malignancies ranging from non‐Hodgkin lymphoma to neuroblastoma. In the former case, ALK is activated as a consequence of a chromosomal translocation and in the latter due to point mutations. In both cases the transforming potential of these oncogenic forms of ALK have been shown in vitro employing traditional cellular transformation assays including 3T3 foci formation. We reasoned that other ALK mutants which have been identified by the Cancer Genome Project may likewise possess transformation potential. We have selected seven ALK mutants identified in cell lines representative of a variety of human cancers based on position within the ALK protein, zygosity and frequency of detection inclu... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5417616 Tue, 15 Nov 2011 05:00:00 +0100 5417616 http://www.medworm.com/index.php?rid=5417615&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21838 AbstractP53 up‐regulated modulator of apoptosis (PUMA) is a critical factor in the intrinsic apoptotic pathway. Through PUMA‐dependent mechanisms, human papillomavirus 16 (HPV16) oncoprotein may affect apoptosis by E6‐mediated p53 degradation. To examine whether the PUMA variants modify the association between HPV16 serology and risk of squamous cell carcinoma of the head and neck (SCCHN), we genotyped two polymorphisms in the PUMA promoter (rs3810294 and rs2032809) in 380 cases and 335 cancer‐free controls of non‐Hispanic Whites, who were frequency‐matched by age (±5 yr), sex, smoking, and drinking status. We found that each individual polymorphism had only a modest impact on risk of SCCHN, particularly in oropharyngeal cancer for rs3810294 and non‐oropharyngeal cancer fo... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5417615 Tue, 15 Nov 2011 05:00:00 +0100 5417615 http://www.medworm.com/index.php?rid=5417614&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21842 AbstractPemetrexed, a new‐generation antifolate, has demonstrated promising single‐agent activity in front‐ and second‐line treatments of non‐small cell lung cancer. However, the molecular mechanism of pemetrexed‐mediated antitumor activity remains unclear. The current study shows that pemetrexed induced DNA damage and caspase‐2, ‐3, ‐8, and ‐9 activation in A549 cells and that treatment with caspase inhibitors significantly abolished cell death, suggesting a caspase‐dependent apoptotic mechanism. The molecular events of pemetrexed‐mediated apoptosis was associated with the activation of ataxia telangiectasia mutated (ATM)/p53‐dependent and ‐independent signaling pathways, which promoted intrinsic and extrinsic apoptosis by upregulating Bax, PUMA, Fas, DR4, and ... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5417614 Tue, 15 Nov 2011 05:00:00 +0100 5417614 http://www.medworm.com/index.php?rid=5417613&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21843 AbstractChronic inflammation is one of the primary causes of colorectal cancer (CRC), and major inflammatory pathways implicated in CRC are cyclooxygenase‐2 (COX‐2) and iNOS; both regulated by nuclear factor‐kappa B (NF‐κB) suggesting that inhibitors of these pathways could be ideal against CRC. Silibinin has shown promising efficacy against various malignancies including CRC, and therefore here we assessed whether silibinin targets NF‐κB activation and associated signaling as a mechanism of its anti‐inflammatory and anti‐cancer effects in CRC. Our results indicated that silibinin treatment (50–200 µM) of human CRC SW480, LoVo, and HT29 cells strongly inhibits tumor necrosis factor α‐induced NF‐κB activation together with decreased nuclear levels of both p65 and ... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5417613 Tue, 15 Nov 2011 05:00:00 +0100 5417613 http://www.medworm.com/index.php?rid=5417612&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20877 In this study, we evaluated chemopreventive efficacy of Antitumor B, a Chinese herbal mixture of six plants (Sophora tonkinensis, Polygonum bistorta, Prunella vulgaris, Sonchus arvensis L., Dictamnus dasycarpus, and Dioscorea bulbifera) on the development of 4‐nitroquinoline‐1‐oxide (4NQO) induced oral squamous cell carcinomas in A/J mice. Antitumor B, delivered through diet, inhibited 4NQO‐induced oral cancer development by 59.19%. The reduction of cell proliferation appears to be associated with efficacy of Antitumor B against 4NQO‐induced oral cancer in A/J mice. The expression of epidermal growth factor receptor (EGFR) and phosphorylated EGFR (Tyr1173) were down‐regulated by Antitumor B. Tissue distribution of Antitumor B was determined using obacunone, matrine, and maackia... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5417612 Tue, 15 Nov 2011 05:00:00 +0100 5417612 http://www.medworm.com/index.php?rid=5417611&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21830 AbstractWe have earlier demonstrated the role of aberrant one‐carbon metabolism in the etiology of breast cancer. In the current study, we examine the clinical utility of these factors in predicting the subtype of breast cancer and as indicators of disease progression. Polymerase chain reaction (PCR)–restriction fragment length polymorphism (RFLP) and PCR–amplified fragment length polymorphism (AFLP) approaches were used for genetic analysis. Plasma folate and homocysteine were measured using Axsym folate kit and reverse phase HPLC, respectively. Multiple linear regression models were used to test the predictability of disease progression. Luminal A subtype was associated with late age of onset, higher body mass index and lack of family history of breast cancer. Thymidylate synthase ... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5417611 Tue, 15 Nov 2011 05:00:00 +0100 5417611 http://www.medworm.com/index.php?rid=5417610&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21831 AbstractDevelopment of resistance to TNF‐related apoptosis‐inducing ligand (TRAIL) in tumor cells is one of the important problems in cancer treatment. Despite the previous report demonstrating that oligomycin suppressed TNF‐induced apoptosis, in our screening of small molecules enhancing cancer cell death to TRAIL, oligomycin A (OMA) was found to enhance TRAIL‐induced apoptosis in HeLa cells. CCAAT/enhancer‐binding protein homologous protein (CHOP) was found to directly bind to death receptor 5 (DR5) promoter through endoplasmic reticulum stress (ER‐stress) signaling and sensitize the cells to TRAIL. Among ER‐stress associated proteins, OMA triggered the inositol‐requiring enzyme 1 (IRE1) signaling pathway, leading to X‐binding protein 1 (XBP1) splicing, CHOP expression ... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5417610 Tue, 15 Nov 2011 05:00:00 +0100 5417610 http://www.medworm.com/index.php?rid=5417609&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21839 AbstractLapatinib, an oral, small‐molecule, reversible inhibitor of both EGFR and HER2, is highly active in HER2 positive breast cancer as a single agent and in combination with other therapeutics. However, resistance against lapatinib is an unresolved problem in clinical oncology. Recently, interest in the use of natural compounds to prevent or treat cancers has gained increasing interest because of presumed low toxicity. Quercetin‐3‐methyl ether, a naturally occurring compound present in various plants, has potent anticancer activity. Here, we found that quercetin‐3‐methyl ether caused a significant growth inhibition of lapatinib‐sensitive and ‐resistant breast cancer cells. Western blot data showed that quercetin‐3‐methyl ether had no effect on Akt or ERKs signaling in... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5417609 Tue, 15 Nov 2011 05:00:00 +0100 5417609 http://www.medworm.com/index.php?rid=5417608&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21834 AbstractTelomerase is a ribonucleoprotein that maintains the ends of chromosomes (telomeres). In normal cells lacking telomerase activity, telomeres shorten with each cell division because of the inability to completely synthesize the lagging strand. Critically shortened telomeres elicit DNA damage responses and limit cellular division and lifespan, providing an important tumor suppressor function. Most human cancer cells express telomerase which contributes significantly to the tumor phenotype. In human breast cancer, telomerase expression is predictive of clinical outcomes such as lymph node metastasis and survival. In mouse models of mammary cancer, telomerase expression is also upregulated. Telomerase overexpression resulted in spontaneous mammary tumor development in aged female mice.... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5417608 Tue, 15 Nov 2011 05:00:00 +0100 5417608 http://www.medworm.com/index.php?rid=5417607&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.21835 In this study, we examined whether bortezomib could enhance response to HDAC inhibition in glioma cells. Although primary cells from glioblastoma multiforme (GBM) patients and established glioma cell lines did not show significant induction of apoptosis with vorinostat treatment alone, the combination of vorinostat plus bortezomib significantly enhanced apoptosis. The enhanced efficacy was due to proapoptotic mitochondrial injury and increased generation of reactive oxygen species. Our results also revealed that combination of bortezomib with vorinostat enhanced apoptosis by increasing Mcl‐1 cleavage, Noxa upregulation, Bak and Bax activation, and cytochrome c release. Further downregulation of Mcl‐1 using shRNA enhanced cell killing by the bortezomib/vorinostat combination. Vorinostat... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5417607 Tue, 15 Nov 2011 05:00:00 +0100 5417607 http://www.medworm.com/index.php?rid=5355387&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20872 In this study, we tested the antiproliferative properties of cladosporol A, the main isoform of this metabolite family, against human cancer cell lines. By assessing cell viability, we found that cladosporol A inhibits the growth of various human colon cancers derived cell lines (HT‐29, SW480, and CaCo‐2) in a time‐ and concentration‐dependent manner, specifically of HT‐29 cells. The reduced cell proliferation was due to a G1‐phase arrest, as assessed by fluorescence activated cell sorting analysis on synchronized HT‐29 cells, and was associated with an early and robust over‐expression of p21waf1/cip1, the well‐known cyclin‐dependent kinases inhibitor. This suggests that the drug may play a role in the control of cancer cell proliferation. Consistently, cyclin D1, c... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5355387 Fri, 28 Oct 2011 02:32:38 +0100 5355387 http://www.medworm.com/index.php?rid=5355388&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20861 This study indicates that major components of the miRNA pathway, such as the microprocessor complex and RISC, are dysregulated in epithelial skin cancer. © 2011 Wiley Periodicals, Inc. (Source: Molecular Carcinogenesis) Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5355388 Mon, 24 Oct 2011 04:00:00 +0100 5355388 http://www.medworm.com/index.php?rid=5343504&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20857 AbstractElastase is the only currently identified target protein for indole‐3‐carbinol (I3C), a naturally occurring hydrolysis product of glucobrassicin in cruciferous vegetables such as broccoli, cabbage, and Brussels sprouts that induces a cell cycle arrest and apoptosis of human breast cancer cells. In vitro elastase enzymatic assays demonstrated that I3C and at lower concentrations its more potent derivative 1‐benzyl‐indole‐3‐carbinol (1‐benzyl‐I3C) act as non‐competitive allosteric inhibitors of elastase activity. Consistent with these results, in silico computational simulations have revealed the first predicted interactions of I3C and 1‐benzyl‐I3C with the crystal structure of human neutrophil elastase, and identified a potential binding cluster on an external ... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5343504 Mon, 24 Oct 2011 01:31:29 +0100 5343504 http://www.medworm.com/index.php?rid=5330603&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20874 AbstractAngiogenesis is a prerequisite for progression of cancers. The number of genes linked to angiogenesis suggests the existence of complex gene‐networks, which remain to be elucidated. To identify angiogenesis genes deregulated in carcinomas, we performed a meta‐profiling analysis of published gene expression microarray studies. Own microarray and quantitative RT‐PCR data were obtained from a colorectal carcinoma cohort. Applying highly stringent inclusion criteria, 15 cancer array studies were suitable for our analysis. These studies provided 789 tumor specimens and 190 samples of healthy tissues yielding a total of approx. 1,000,000 gene expression measurements. Meta‐analysis on the expression of 480 angiogenesis‐related genes in 10 cancer types identified a characteristic... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5330603 Wed, 19 Oct 2011 20:34:29 +0100 5330603 http://www.medworm.com/index.php?rid=5330612&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20875 AbstractThe renal cell carcinoma (RCC) is one of the top 10 cancers in USA. The renal tumors are highly angiogenic and are resistant to conventional interventions, particularly radiotherapy. The advent of multi‐specific tyrosine kinase inhibitor sorafenib has improved the progression‐free survival in RCC, but overall survival in recurrent and metastatic RCC is still a concern that has lead to characterization of combinatorial regimens. Hence, we studied the effect of combination of nutlin‐3, an MDM2 inhibitor, which increases p53 levels, and sorafenib in RCC. Sorafenib along with nutlin‐3 synergistically inhibited the cell survival and enhanced caspase‐3 cleavage leading to apoptosis in RCC. Nutlin‐3 and sorafenib were more effective in reducing the migration of RCC, in combina... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5330612 Mon, 17 Oct 2011 04:00:00 +0100 5330612 http://www.medworm.com/index.php?rid=5330611&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20870 AbstractMultiple studies have shown a link between chronic inflammation and lung tumorigenesis. Inbred mouse strains vary in their susceptibility to methylcholanthrene (MCA)‐initiated butylated hydroxytoluene (BHT)‐promoted lung carcinogenesis. In the present study we investigated whether neutrophils play a role in strain dependent differences in susceptibility to lung tumor promotion. We observed a significant elevation in homeostatic levels of neutrophils in the lungs of tumor‐susceptible BALB/cByJ (BALB) mice compared to tumor‐resistant C57BL/6J (B6) mice. Additionally, BHT treatment further elevated neutrophil numbers as well as neutrophil chemoattractant keratinocyte‐derived cytokine (KC)/chemokine (C‐X‐C motif) ligand 1 (Cxcl1) levels in BALB lung airways. Lung CD11c+ c... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5330611 Mon, 17 Oct 2011 04:00:00 +0100 5330611 http://www.medworm.com/index.php?rid=5330610&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20873 AbstractIn this paper we report a new myeloid differentiation effect of bortezomib (BTZ) in acute myeloid leukemia (AML) cell lines and primary patient‐derived AML cells; this effect was assayed by investigating growth‐inhibition, cell morphology, differentiation markers, and nitro‐blue tetrazolium reduction. We show that BTZ induces the phosphorylation of several mitogen‐activated protein (MAP) kinases, including MEK/ERK, c‐Jun N‐terminal kinase (JNK), and p38 MAPK. BTZ‐induced cell differentiation is almost completely reversed by PD98059, an inhibitor of MEK, which also attenuates the increase in phospho‐JNK p46. However, p38 activation does not appear to be required for the differentiation induced by BTZ. Furthermore, the differentiation effect of BTZ is associated with ... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5330610 Mon, 17 Oct 2011 04:00:00 +0100 5330610 http://www.medworm.com/index.php?rid=5330609&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20871 AbstractRecent investigations have demonstrated the clear heterogeneity of sporadic colorectal cancer (CRC) with regard to CpG island methylation. Two unsupervised cluster analyses revealed that CRCs form three distinct DNA methylation subsets, which are referred to as the high‐, intermediate‐, and low‐methylation epigenotypes (HME, IME, and LME, respectively). A recent study by Yagi et al. found a fairly sensitive and specific identification of HME, IME, and LME using two marker panels analyzed by MALDI‐TOF mass spectrometry (MassARRAY). However, the expensive equipment required for this method substantially increases the cost and complexity of the assay. In this article, we demonstrate the assessment of HME, IME, and LME in a group of 233 sporadic CRCs using seven markers propose... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5330609 Mon, 17 Oct 2011 04:00:00 +0100 5330609 http://www.medworm.com/index.php?rid=5330608&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20868 AbstractStudies show that elevated insulin‐like growth factor‐1 (IGF‐1) levels are associated with an increased risk of breast cancer; however, mechanisms through which IGF‐1 promotes mammary tumorigenesis in vivo have not been fully elucidated. To assess the possible involvement of COX‐2 signaling in the pro‐tumorigenic effects of IGF‐1 in mammary glands, we used the unique BK5.IGF‐1 mouse model in which transgenic (Tg) mice have significantly increased incidence of spontaneous and DMBA‐induced mammary cancer compared to wild type (WT) littermates. Studies revealed that COX‐2 expression was significantly increased in Tg mammary glands and tumors, compared to age‐matched WTs. Consistent with this, PGE2 levels were also increased in Tg mammary glands. Analysis of expre... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5330608 Mon, 17 Oct 2011 04:00:00 +0100 5330608 http://www.medworm.com/index.php?rid=5330607&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20866 AbstractApigenin (4′,5,7,‐trihydroxyflavone), an anticancer agent, selectively toxic to cancer cells induces cell cycle arrest and apoptosis through mechanisms that have not been fully elucidated. Our studies indicate that apigenin‐mediated growth inhibitory responses are due to inhibition of class I histone deacetylases (HDACs) in prostate cancer cells. Treatment of PC‐3 and 22Rv1 cells with apigenin (20–40 µM) resulted in the inhibition of HDAC enzyme activity, specifically HDAC1 and HDAC3 at the protein and message level. Apigenin‐mediated HDAC inhibition resulted in global histone H3 and H4 acetylation, as well as localized hyperacetylation of histone H3 on the p21/waf1 promoter. A corresponding increase was observed in p21/waf1 and bax protein and mRNA expression after ... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5330607 Mon, 17 Oct 2011 04:00:00 +0100 5330607 http://www.medworm.com/index.php?rid=5330606&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20869 AbstractHumans express sulfotransferases (SULTs) of the SULT1A subfamily in many tissues, whilst the single SULT1A gene present in rodents is mainly expressed in liver. The food processing contaminants, 5‐hydroxymethylfurfural (HMF) and 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP), are bioactivated by human SULT1A1 and SULT1A2. FVB multiple intestinal neoplasia (Min) mice, which spontaneously develop tumors and flat aberrant crypt foci (ACF) in intestine, were crossed with transgenic FVB mice expressing human SULT1A1 and 1A2 (hSULT) in several tissues, giving rise to wild‐type and Min mice with and without hSULT. One‐week‐old Min mice with or without hSULT were given HMF (375 or 750 mg/kg bw) or saline by gavage three times a week for 11 wk. In another exp... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5330606 Mon, 17 Oct 2011 04:00:00 +0100 5330606 http://www.medworm.com/index.php?rid=5330605&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20867 Abstract2‐methoxyestradiol (2ME2), an endogenous metabolite of 17‐β‐estradiol, has been shown to induce apoptosis and cell cycle arrest in various tumor models. We have previously shown that 2ME2 induced endoreduplication in a well‐differentiated nasopharyngeal carcinoma (NPC) HK‐1 and a poorly differentiated C666‐1 cell line. In the present study, we studied the survival factors involved in 2ME2‐induced endoreduplicating NPC cells. In the HK‐1 cells, knockdown of BcL‐xL expression by siRNA resulted in the reduction of endoreduplication and an increase in the percentage of apoptosis. Further mechanistic study revealed that 2ME2 enhanced the expression of the phosphorylated form of STAT5 (p‐STAT5‐Y694), but not p‐STAT3 (Y705) and p‐STAT3 (S727), in the nucleus of ... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5330605 Mon, 17 Oct 2011 04:00:00 +0100 5330605 http://www.medworm.com/index.php?rid=5330604&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20862 AbstractResults from recent molecular epidemiologic studies suggest that the core circadian genes play a role in breast tumorigenesis, possibly by influencing hormone regulation or other pathways relevant to cancer. In order to further evaluate this hypothesis, we conducted a genetic and epigenetic association study of the circadian regulator TIMELESS in breast carcinogenesis. We detected significant associations between two tagging SNPs (rs2291738 and rs7302060) in the TIMELESS gene and breast cancer among 441 breast cancer cases and 479 cancer‐free controls, with apparent effect modification by ER/PR status. The presence of the C allele of rs7302060 was found to be associated with reduced breast cancer risk (OR, 0.54; 95% CI, 0.54–0.99). In addition, both the G/G genotype of rs229173... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5330604 Mon, 17 Oct 2011 04:00:00 +0100 5330604 http://www.medworm.com/index.php?rid=5292891&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20865 This study addressed whether Notch2 signal pathway is also involved in gastric cancer progression. Constitutive expression of Notch2 intracellular domain (N2IC), the activated form of Notch2 receptor, promoted both cell proliferation and xenografted tumor growth of human stomach adenocarcinoma SC‐M1 cells. The colony formation, migration, invasion, and wound‐healing abilities of SC‐M1 cells were enhanced by N2IC expression, whereas these abilities were suppressed by Notch2 knockdown. Similarly, Notch2 knockdown inhibited cancer progressions of AGS and AZ521 gastric cancer cells. Expression of N2IC also caused epithelial–mesenchymal transition in SC‐M1 cells. Furthermore, N2IC bound to COX‐2 promoter and induced COX‐2 expression through a CBF1‐dependent manner in SC‐M1 cel... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5292891 Tue, 04 Oct 2011 04:00:00 +0100 5292891 http://www.medworm.com/index.php?rid=5292890&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20863 AbstractTo explore the associations of SNPs within hsa‐miR‐605 (rs2043556) and hsa‐miR‐149 (rs2292832) and lifestyle‐related factors with gastrointestinal cancer, a case–control study including 762 cases and 757 controls was conducted. Marginally significant associations were found both for hsa‐miR‐149 rs2292832 with gastric cancer risk (TC + CC vs. TT, OR = 0.68, 95% CI: 0.44–1.04) and for hsa‐miR‐605 rs2043556 with colorectal cancer risk (AG + GG vs. AA, OR = 0.70, 95% CI: 0.48–1.02) in males. Tea drinking showed a protective effect on gastric cancer risk (OR = 0.28, 95% CI: 0.13–0.60), while smoke inhalation increased the risk of gastric cancer (OR = 1.94, 95% CI: 1.08–3.47). Irritability was found to be a risk factor for both colorect... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5292890 Tue, 04 Oct 2011 04:00:00 +0100 5292890 http://www.medworm.com/index.php?rid=5292889&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20858 We examined the relationship between 240 SNPs in DNA repair and cell cycle control pathway genes and lung cancer risk in a case–control study of white current and ex‐cigarette smokers (722 cases and 929 controls). Additive, dominant, and recessive genetic models were evaluated for each SNP. A genetic risk summary score was also constructed. Odds ratios (OR) for lung cancer risk and 95% confidence intervals (95% CI) were estimated using logistic regression models. Thirty‐eight SNPs were associated with lung cancer risk in our study population at P < 0.05. The strongest associations were observed for rs2074508 in GTF2H4 (Padditive = 0.003), rs10500298 in LIG1 (Precessive = 2.7 × 10−4), rs747658 and rs3219073 in PARP1 (rs747658: Padditive = 5.8 × 10−5; r... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5292889 Tue, 04 Oct 2011 04:00:00 +0100 5292889 http://www.medworm.com/index.php?rid=5292888&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20864 AbstractThe universal cyclin‐dependent kinase inhibitor p21WAF1/Cip1 promotes cell cycle arrest and inhibits apoptosis in response to UV‐induced DNA damage. Since the protein kinase ATR plays a major role in the cellular response to these carcinogenic lesions, we investigated the possible role of ATR in the modulation of p21WAF1/Cip1 expression in response to UVC radiation. We have shown that p21WAF1/Cip1 is up‐regulated in human fibroblast and epithelial cells, but only in response to low UV fluences and low passage cells. Importantly, this up‐regulation is ATR‐dependent. In fact, in ATR‐deficient or caffeine‐treated cells UV light rather down‐regulated the p21WAF1/Cip1 protein through SKP2‐dependent ubiquitination and degradation via the proteasomal pathway. Furthermore... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5292888 Tue, 04 Oct 2011 04:00:00 +0100 5292888 http://www.medworm.com/index.php?rid=5292887&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20859 We describe how performing splicing factor‐specific comparisons using both tumor and cell line data sets may more readily identify physiologically relevant tumor‐specific splicing events. Affymetrix exon array data derived from glioblastoma (GBM) tumor samples with defined polypyrimidine tract‐binding protein 1 (PTBP1) levels were compared with data from U251 GBM cells with and without PTBP1 knockdown. This comparison yielded overlapping gene sets that comprised only a minor fraction of each data set. The identification of a novel GBM‐specific splicing event involving the USP5 gene led us to further examine its role in tumorigenesis. In GBM, USP5 generates a shorter isoform 2 through recognition of a 5′ splice site within exon 15. Production of the USP5 isoform 2 was strongly cor... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5292887 Tue, 04 Oct 2011 04:00:00 +0100 5292887 http://www.medworm.com/index.php?rid=5292886&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20860 AbstractSmoking is the main risk factor for urothelial bladder cancer. In former smokers the risk decreases but does not reach the low level of never smokers. This indicates reversible and permanent smoking‐derived genetic alterations. Transcriptional changes may point to mechanisms, how smoking promotes urothelial bladder cancer. To identify smoking‐derived transcriptional changes we performed gene expression profiling in current, former, and never smokers, using tumor and tumor‐free urothelium from patients with nonmuscle‐invasive urothelial bladder cancer (NMIBC) or muscle‐invasive urothelial bladder cancer (MIBC). Smoking turned out to influence gene expression much less than tumor stage (NMIBC or MIBC) and tumor transformation (tumor‐free or tumor). Smoking seemed to influ... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5292886 Sat, 01 Oct 2011 04:00:00 +0100 5292886 http://www.medworm.com/index.php?rid=5233430&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20856 AbstractWe evaluated whether high‐fat diet (HFD), in the absence of increased calorie intake, increases colon cancer growth and metastasis. Four‐week‐old male BALB/c mice were fed on an HFD (60 kcal% fat) or control diet (10 kcal% fat) for 16 wk, after which CT26 colon cancer cells were subcutaneously injected into the right flank. Solid tumor growth and the number and volume of tumor nodules in the lung were increased markedly in the HFD group with only a slight increase in body weight (5.9%). HFD feeding increased tumor tissue levels of Ki67, cyclin A, cyclin D1, CDK2, Bcl‐xL, and Bcl‐2; reduced p53 levels and TUNEL‐positive apoptotic cells; increased the levels of CD45, CD68, CD31, VEGF, P‐VEGF receptor‐2, iNOS, and COX‐2 as well as hemoglobin content; and increa... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5233430 Tue, 20 Sep 2011 00:38:50 +0100 5233430 http://www.medworm.com/index.php?rid=5191173&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20851 AbstractSilibinin inhibits mouse lung tumorigenesis in part by targeting tumor microenvironment. Tumor necrosis factor‐alpha (TNF‐α) and interferon‐gamma (IFN‐γ) can be pro‐ or anti‐tumorigenic, but in lung cancer cell lines they induce pro‐inflammatory enzymes cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS). Accordingly, here we examined mechanism of silibinin action on TNF‐α + IFN‐γ (hereafter referred as cytokine mixture) elicited signaling in tumor‐derived mouse lung epithelial LM2 cells. Both signal transducers and activators of the transcription (STAT)3 (tyr705 and ser727) and STAT1 (tyr701) were activated within 15 min of cytokine mixture exposure, while STAT1 (ser727) activated after 3 h. Cytokine mixture also activated Erk1/2 and ... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5191173 Sun, 04 Sep 2011 03:07:38 +0100 5191173 http://www.medworm.com/index.php?rid=5179192&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20843 AbstractAllelic imbalances at chromosome 4p have been largely documented in many different tumor types. In colorectal cancer, loss of heterozygosity (LOH) at 4p15 has been associated with tumor aggressiveness and poor patient outcome, however no target genes in the region have been identified to date. Since stromal interaction molecule 2 (STIM2) is located at 4p15.2 and has been proposed as a candidate gene for this region in glioblastoma multiforme, we aimed at investigating the role of STIM2 in colorectal cancer. We studied STIM2 transcript expression levels in a collection of xenografted primary colorectal tumors (n = 20) and a well‐annotated tumor series of colorectal cancer (n = 140). We observed an overexpression of STIM2 in 63.5% of the cases that was associated with a les... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5179192 Wed, 31 Aug 2011 03:15:49 +0100 5179192 http://www.medworm.com/index.php?rid=5191181&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20844 In this study, we used our chronic carcinogenesis model as a target system to investigate the activity of green tea catechin extract (GTC) at non‐cytotoxic levels in intervention of cellular carcinogenesis induced by cumulative exposures to pico‐molar 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK) and benzo[a]pyrene (B[a]P). We identified that GTC, at a non‐cytotoxic, physiologically achievable concentration of 2.5 µg/mL, was effective in suppressing NNK‐ and B[a]P‐induced cellular carcinogenesis, as measured by reduction of the acquired cancer‐associated properties of reduced dependence on growth factors, anchorage‐independent growth, increased cell mobility, and acinar‐conformational disruption. We also detected that intervention of carcinogen‐induc... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5191181 Tue, 30 Aug 2011 23:00:00 +0100 5191181 http://www.medworm.com/index.php?rid=5191180&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20846 AbstractCelecoxib, a selective cyclooxygenase‐2 (COX‐2) inhibitor, has been reported to exert chemopreventive and antitumor effects on colon cancer, one of the most common solid epithelial malignancy worldwide. The aim of this study was to elucidate whether celecoxib may be able to affect epithelial–mesenchymal transition (EMT), a critical process involved in cancer cell invasiveness and metastasis and then proposed to be relevant for cancer progression. Human HT‐29 colon cancer cells were exposed to carefully controlled hypoxic conditions and/or epidermal growth factor (EGF) and then investigated for EMT changes and signal transduction pathways involved by using morphological, molecular, and cell biology techniques. Celecoxib inhibited basal and EGF‐stimulated proliferation, hyp... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5191180 Tue, 30 Aug 2011 23:00:00 +0100 5191180 http://www.medworm.com/index.php?rid=5191179&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20848 AbstractWe and others have identified FGFR4 as a direct transcriptional target of the alveolar rhabdomyosarcoma (ARMS) specific fusion protein, PAX3‐FOXO1. We hypothesized fibroblast growth factor receptor 4 (FGFR4) may act as an effector of PAX3‐FOXO1, contributing to PAX3‐FOXO1 tumorigenic phenotypes. However, we demonstrate that enhanced expression of FGFR4 does not contribute to inhibited differentiation, enhanced proliferation, or transformation downstream of PAX3‐FOXO1 in primary mouse myoblasts. Therefore we were unable to identify any contribution of up regulation of wild type FGFR4 to PAX3‐FOXO1 driven tumorigenesis. Conversely, a constitutively active mutant of FGFR4 can enhance primary myoblast proliferation and transformation, indicating activating mutations of FGFR4 ... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5191179 Tue, 30 Aug 2011 23:00:00 +0100 5191179 http://www.medworm.com/index.php?rid=5191178&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20849 AbstractActivation of Ras and its downstream signaling pathways, likely contribute to the development of hepatocarcinoma. We have previously shown that intraperitoneal injections of the Ras inhibitor S‐trans, trans‐farnesylthiosalicyclic acid (FTS) blocks Ras activation and prevents heptocarcinoma development in rats receiving weekly injections of the carcinogene diethylnitrosamine (DEN) for 16 wk. Using this in vivo model, we evaluated the relationship between the tumor preventive effect of Ras inhibition and activation of downstream signaling pathways, cell proliferation, cell cycle events, and angiogenesis. Western blotting, quantitative PCR, immunohistochemistry, and transcription factor activity assays were used. DEN‐induced activation of NFkB and Stat3 was abrogated by FTS tr... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5191178 Tue, 30 Aug 2011 23:00:00 +0100 5191178 http://www.medworm.com/index.php?rid=5191177&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20850 AbstractRecently unbiased sequencing efforts identified PPP2R1A mutations in clear cell ovarian cancers (OCC). Similar mutations were also noted with high frequency in uterine serous carcinoma. Because the endometrium develops from the same developmental precursors we further examined the hypothesis that PPP2R1A mutations might also occur in diverse histologic subtypes of uterine cancer. We sequenced the PPP2R1A in 22 cell line models of uterine cancer and 10 primary cancers. We found no mutations in the cell lines originally derived from endometrioid (n = 13), undifferentiated (n = 3), clear cell (n = 1), and carcinosarcoma (n = 3) cancers. However, we found a CCC (Pro) to CGC (Arg) codon 179 mutation in the ACI‐158 serous carcinoma cell line, a CCC (Pro) to CTC (Leu) in... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5191177 Tue, 30 Aug 2011 23:00:00 +0100 5191177 http://www.medworm.com/index.php?rid=5191176&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20852 AbstractBasal cell carcinoma of the skin typically carries genetic alterations in components of the hedgehog (HH) signaling pathway. Previously, we generated a knockout mouse with a loss‐of‐function mutation in suppressor of fused (Sufu), an essential repressor of the pathway downstream of Hh ligand cell surface reception. Mice heterozygous for the mutated Sufu allele develop a skin phenotype that includes lesions similar to basaloid follicular hamartomas. The purpose of the current study was to test the possibility that the simultaneous loss of the tumor suppressor gene, transformation related protein 53 (Trp53), would aggravate the Sufu skin phenotype since Trp53 loss is known to enhance the growth of other Hh‐driven tumors. Consistent with previous reports, medulloblastomas and rh... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5191176 Tue, 30 Aug 2011 23:00:00 +0100 5191176 http://www.medworm.com/index.php?rid=5191175&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20854 AbstractThe aim of this study is to evaluate the role of adipose tissue resident stromal cells on tumor cell invasion. Our data show that a subpopulation of adipose tissue derived stromal cells expressing Nestin, NG2, α‐smooth muscle actin and PDGFR‐α migrate toward the cancer cells. Microarray analysis revealed the upregulation of IL‐8 in the migrated cells. We demonstrated that stromal cell derived IL‐8 promote the invasion and the anchorage‐independent growth of cancer cells. We conclude that human breast cancer cells attract a subpopulation of stromal cells that secrete IL‐8 to promote tumor cell invasion in a paracrine fashion. © 2011 Wiley‐Liss, Inc. (Source: Molecular Carcinogenesis) Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5191175 Tue, 30 Aug 2011 23:00:00 +0100 5191175 http://www.medworm.com/index.php?rid=5191174&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20853 AbstractGlioblastoma cells are characterized by high proliferation and invasive capacities. Tumor development has been associated with a decrease of gap‐junctional intercellular communication, but the concrete involvement of gap junction proteins, connexins, remains elusive since they are also suspected to promote cell invasion. In order to better understand how connexins control the glioma cell phenotype, we studied the consequences of inhibiting the intrinsic expression of the major astrocytic connexin, Connexin43, in human U251 glioblastoma cells by the shRNA strategy. The induced down‐regulation of Cx43 expression has various effects on the U251 cells such as increased clonogenicity, angiogenesis and decreased adhesion on specific extracellular matrix proteins. We demonstrate that ... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5191174 Tue, 30 Aug 2011 23:00:00 +0100 5191174 http://www.medworm.com/index.php?rid=5179194&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20847 AbstractTropomyosins (TMs) are a family of cytoskeletal proteins that bind to and stabilize actin microfilaments. Non‐muscle cells express multiple isoforms of TMs including three high molecular weight (HMW) isoforms: TM1, TM2, and TM3. While reports have indicated downregulation of TMs in transformed cells and several human cancers, nevertheless, little is known about the underlying mechanism of TMs suppression. In present study the expression of HMW TMs was investigated in squamous cell carcinoma of esophagus (SCCE), relative to primary cell cultures of normal esophagus by western blotting and real‐time RT‐PCR. Our results showed that TM1, TM2, and TM3 were significantly downregulated in cell line of SCCE. Moreover, mRNA level of TPM1 and TPM2 were markedly decreased by 93% and 96%... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5179194 Mon, 29 Aug 2011 23:00:00 +0100 5179194 http://www.medworm.com/index.php?rid=5179193&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20845 AbstractPancreatic cancer is the fourth leading cause of cancer death in the United States because most patients are diagnosed too late in the course of the disease to be treated effectively. Thus, there is a pressing need to more clearly understand how gene expression is regulated in cancer cells and to identify new biomarkers and therapeutic targets. Translational regulation is thought to occur primarily through non‐SMAD directed signaling pathways. We tested the hypothesis that SMAD4‐dependent signaling does play a role in the regulation of mRNA entry into polysomes and that novel candidate genes in pancreatic cancer could be identified using polysome RNA from the human pancreatic cancer cell line BxPC3 with or without a functional SMAD4 gene. We found that (i) differentially expres... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5179193 Mon, 29 Aug 2011 23:00:00 +0100 5179193 http://www.medworm.com/index.php?rid=5155614&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20842 AbstractMatrix metallopeptidases (MMPs) play an important role in central nervous system tumor growth, invasion and spreading. The currently available data provide clear evidence for the involvement of MMP3 in the pathophysiology of glioma. The study aims to explore the association of single nucleotide polymorphisms (SNPs) across the MMP3 gene with glioma risk. Three haplotype tagging and additional two promoter SNPs were genotyped among 766 glioma patients and 824 cancer‐free controls from East China. None of these polymorphisms alone had a significant effect on risk of gliomas. However, when three promoter polymorphisms were evaluated together by the number of putative risk of genotypes (i.e., rs645419AA, 632478CA+AA, rs522616AA), a statistically significantly increased risk of gliomas... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5155614 Thu, 25 Aug 2011 07:34:25 +0100 5155614 http://www.medworm.com/index.php?rid=5155615&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20840 AbstractUVB radiation is the major carcinogen responsible for skin carcinogenesis, thus elucidation of the molecular pathways altered in skin in response to UVB would reveal novel targets for therapeutic intervention. It is well established that UVB leads to upregulation of cyclooxygenase 2 (COX‐2) in the skin which contributes to skin carcinogenesis. Overexpression of COX‐2 has been shown to promote colon cancer cell growth through β‐catenin signaling, however, little is known about the connection between UVB, COX‐2, and β‐catenin in the skin. In the present study, we have identified a novel pathway in which UVB induces β‐catenin signaling in keratinocytes, which is modulated by COX‐2 expression. Exposure of the mouse 308 keratinocyte cell line (308 cells) and primary nor... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5155615 Wed, 17 Aug 2011 23:00:00 +0100 5155615 http://www.medworm.com/index.php?rid=5117083&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20841 This study demonstrated that the effectiveness of I3C as prostate cancer chemoprevention agent via up‐regulation of a novel Nrf2‐mediated anti‐oxidative stress pathway. © 2011 Wiley‐Liss, Inc. (Source: Molecular Carcinogenesis) Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5117083 Thu, 11 Aug 2011 17:14:37 +0100 5117083 http://www.medworm.com/index.php?rid=5117087&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20835 In conclusion, the overexpression of ΔNp73β increases viability in p53 wild type and p53 mutant colon cancer cells, and cisplatin induces the degradation of ΔNp73β in a dose‐dependent manner. © 2011 Wiley‐Liss, Inc. (Source: Molecular Carcinogenesis) Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5117087 Wed, 10 Aug 2011 23:00:00 +0100 5117087 http://www.medworm.com/index.php?rid=5117086&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20836 AbstractN‐acetyltransferase 1 (NAT1) is a phase II metabolic enzyme responsible for the biotransformation of aromatic and heterocyclic amine carcinogens such as 4‐aminobiphenyl (ABP). NAT1 catalyzes N‐acetylation of arylamines as well as the O‐acetylation of N‐hydroxylated arylamines. O‐acetylation leads to the formation of electrophilic intermediates that result in DNA adducts and mutations. NAT1 is transcribed from a major promoter, NATb, and an alternative promoter, NATa, resulting in mRNAs with distinct 5′‐untranslated regions (UTR). NATa mRNA is expressed primarily in the kidney, liver, trachea, and lung while NATb mRNA has been detected in all tissues studied. To determine if differences in 5′‐UTR have functional effect upon NAT1 activity and DNA adducts or mutati... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5117086 Wed, 10 Aug 2011 23:00:00 +0100 5117086 http://www.medworm.com/index.php?rid=5117085&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20838 We report on an ovarian cancer patient who carries a germline MSH2 c.1A>C variant which alters the translation initiation codon. Mutations affecting the MSH2 start codon have been described previously for LS‐related malignancies. However, the patients often lack a clear family history indicative of LS and their tumors often fail to display microsatellite instability, a hallmark feature of LS. Therefore, the pathogenicity of start codon variants remains undefined. Loss of the MSH2 start codon has been predicted to result in a truncated protein translated from a downstream in‐frame AUG that would lack the first 25 amino acids. We therefore purified recombinant MSH2(NΔ25)‐MSH6 and MSH2(NΔ25)‐MSH3 to examine their DNA lesion recognition and adenosine nucleotide processing function... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5117085 Wed, 10 Aug 2011 23:00:00 +0100 5117085 http://www.medworm.com/index.php?rid=5117084&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20839 In this study, we investigated the role of Tg737 in the malignant transformation of fetal liver stem/progenitor cells (FLSPCs). We inhibited Tg737 in FLSPCs using short hairpin RNA (shRNA). The microscopic observations of freshly purified Tg737 normal FLSPCs (nFLSPCs) and Tg737‐silent FLSPCs (sFLSPCs), which showed high expression levels of stem cell markers, revealed no significant morphological changes in sFLSPCs. Following RNAi of Tg737, the mRNA and protein levels of sFLSPCs decreased by 81.81% and 80.10% as shown by PCR, Western blot and immunocytochemistry analyses. Excluding apoptosis‐related effects, we found that silencing of Tg737 resulted in enhanced cell proliferation through promoting cell‐cycle progression via upregulation of cyclin D1 and cyclin B expression (P <�... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5117084 Wed, 10 Aug 2011 23:00:00 +0100 5117084 http://www.medworm.com/index.php?rid=5085228&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20834 AbstractInterleukin‐9 (IL‐9) is a multifunctional cytokine that not only has roles in immune and inflammatory responses but also is involved in growth‐promoting and anti‐apoptotic activities in multiple transformed cell lines, which suggests a potential role in tumorigenesis. Over‐expression of the receptor of IL‐9 (IL‐9R) occurs in several types of human leukemias and in radiation‐induced mouse T‐cell lymphoma (TL). The molecular mechanism that regulates transcription of the IL‐9R gene (Il9r) during leukemogenesis is, however, not well understood. Using a mouse TL cell line that has high expression of Il9r, we sought to dissect its promoter structure. Here we show that the active promoter for Il9r is located in the 5′‐flanking AT‐rich region. Chromatin immunoprec... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5085228 Tue, 02 Aug 2011 04:26:21 +0100 5085228 http://www.medworm.com/index.php?rid=5085232&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20830 AbstractThe P53 gene is a tumor suppressor gene and can prevent mutation and tumor induction though apoptosis and DNA repair when it is activated by genotoxic stress. miR‐34a expression is regulated by the P53 gene and might be required for cell response to DNA damage. TK6 cells are human lymphoblast cells with normal P53 function while WTK1 and NH32 cells derived from the same progenitor as TK6 cells are P53‐deficient. Previous mutation research showed an unexpected result that NH32 cells were much less mutable than WTK1 cells, although the P53 gene in both the cell lines is not functional. To explore the possible mechanisms involved in the different mutability of the cell lines and relationship between P53 and miR‐34a, we investigated the expression levels of miR‐34a in the cells... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5085232 Sun, 31 Jul 2011 23:00:00 +0100 5085232 http://www.medworm.com/index.php?rid=5085231&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20831 AbstractTesticular germ cell tumors (TGCTs) have a unique epigenetic profile distinct from that of other types of cancer. To further evaluate epigenetics of TGCTs, this study examines DNA methylation patterns of DNA repetitive elements in TGCTs. Bisulfite genomic sequencing and combined bisulfite restriction analysis (COBRA) were used to analyze the methylation patterns of DNA repetitive elements (LINE1 and Alu repeats) in embryonal carcinoma (EC) derived cell lines, primary TGCT tissues, noncancerous testicular tissues adjacent to TGCTs and cancer cells derived from somatic tissues (testicular malignant lymphoma tissues and renal cell carcinoma cell lines). Through both bisulfite genomic sequencing and COBRA, LINE1 was extensively hypomethylated in both seminomatous and nonseminomatous TG... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5085231 Sun, 31 Jul 2011 23:00:00 +0100 5085231 http://www.medworm.com/index.php?rid=5085230&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20837 This study aimed to understand the importance of RASSF1A and CACNA2D2, located in chromosomal 3p21.31 region, in the development of uterine cervical carcinoma (CACX). To this end, firstly the expression (RNA) profiles of RASSF1A and CACNA2D2 were screened in primary cervical carcinoma (CACX) samples which indicated highly reduced expression for both genes. Thereafter alterations (deletion/methylation) of these genes were analyzed in 23 cervical intraepithelial neoplasia (CIN) and 110 CACX samples. In CIN, deletion was observed only for RASSF1A (26%), whereas methylation was in the following order: RASSF1A (35%) > CACNA2D2 (9%). However, in CACX their deletion frequencies were the same (50%) and methylation frequencies were comparable RASSF1A (33%), CACNA2D2 (27%). The reduced expres... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5085230 Sun, 31 Jul 2011 23:00:00 +0100 5085230 http://www.medworm.com/index.php?rid=5085229&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20832 AbstractMelatonin inhibits growth and invasive capacity of colon cancer cells in vitro through its membrane (MT1 and MT2) and/or nuclear receptors (RORα). Previous studies showed that this indoleamine is present in both the normal and colon cancer at similar levels. Therefore, we analyzed MT1, MT2, and RORα expression in tumor samples versus normal mucosa (NM) from patients suffering from colorectal cancer (CRC). Given the existence of sex differences in the incidence and pathology of CRC and the involvement of steroid receptors in the oncostatic actions of melatonin in some types of cancer, we also analyzed the expression of androgen (AR) and estrogen receptor (ER) α and ERβ. Finally, we conducted some experiments in colon cancer cell lines to corroborate the experiments carried out i... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5085229 Sun, 31 Jul 2011 23:00:00 +0100 5085229 http://www.medworm.com/index.php?rid=5048282&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20828 AbstractHost immune responses are critical steps for carcinogenesis. Single nucleotide polymorphisms (SNPs) in immunoregulatory genes may influence gastric cancer risk. We performed a genotyping analysis for immunoregulatory genes in 311 gastric cancer cases and 425 controls from a Chinese population. We found that there were significant differences of E‐selectin variant rs5361 (A>C) and FCGR2A variant rs1801274 (T>C) between cases and controls (P = 0.022 and P = 0.0001, respectively). Logistic regression analysis indicated that genotype of E‐selectin rs5361AC increased the risk of gastric cancer significantly (P = 0.026, adjusted Odds ratio (OR) = 2.84, 95% confidence interval (CI) = 1.13–7.12). C allele of E‐selectin rs5361 showed a significant increased... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5048282 Thu, 21 Jul 2011 23:44:01 +0100 5048282 http://www.medworm.com/index.php?rid=5048283&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20825 AbstractRetinoblastoma (Rb) is a common childhood intraocular cancer that affects approximately 300 children each year in the United States alone. 2‐Methoxyestradiol (2ME), an endogenous metabolite of 17‐β‐estradiol that dose not bind to nuclear estrogen receptor, exhibits potent apoptotic activity against rapidly growing tumor cells. Here, we report that 2ME induction of apoptosis was demonstrated by early fragmented DNA after 48 h of incubation with 10 µM 2ME in Rb cell lines. Subsequently, a decrease of proliferation was observed in a time‐ and dose‐dependent manner. Further analysis of the mechanism indicates that p38 kinase plays a critical role in 2ME‐induced apoptosis in Y79 cells, even though ERK was also activated by 2ME under the same conditions. Activation of p... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5048283 Sun, 17 Jul 2011 23:00:00 +0100 5048283 http://www.medworm.com/index.php?rid=5026817&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20829 AbstractSurvivin is involved in multiple signaling mechanisms in tumor maintenance, and accumulated studies elucidate that knockdown of survivin in endothelial cells could inhibit angiogenesis; however, the role of survivin in tumor cells to regulate tumor‐derived angiogenesis remains largely unclear. In the present study 80 cases of brain glioma were chosen and protein expressions of survivin, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and platelet‐derived growth factor (PDGF) in glioma cells were investigated by immunohistochemistry (IHC). Human umbilical vein endothelial cells (HUVEC) were cocultured with human glioma U251 wild‐type cells, U251 cells survivin silenced, SHG44 wild‐type cells, and SHG44 survivin‐overexpressing cells, respec... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5026817 Thu, 14 Jul 2011 22:00:47 +0100 5026817 http://www.medworm.com/index.php?rid=5017807&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20699 This study aimed to elucidate the possible participation of HNE, GSH/GST system, and EGFR signaling in hESCC development. Immunohistochemistry of HNE adducts, EGFR, and phosphorylated EGFR (pEGFR) was performed with hESCC specimens. The effect of HNE on the phosphorylation of EGFR and its downstream PhospholipaseCγ1 (PLCγ1) was investigated with KYSE30 cell‐line. Pretreatment with GSH inducer N‐acetylcysteine (NAC) or GSH inhibitor Buthionine sulfoximine (BSO) and mandatory transfection of hGSTA4 gene in KYSE30 were conducted to investigate the relationship between HNE and GSH/GST system. Immunoreactants of HNE adducts, EGFR, and pEGFR were increased in hESCC compared to non‐cancerous epithelium with positive correlations. The treatment of HNE ligand‐independently induced the pho... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5017807 Tue, 12 Jul 2011 20:38:27 +0100 5017807 http://www.medworm.com/index.php?rid=5017810&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20821 In this study, we examined the ability of a novel cyano derivative of 11‐keto‐β‐boswellic acid, that is, butyl 2‐cyano‐3,11‐dioxours‐1,12‐dien‐24‐oate (BCDD) to induce apoptosis in cancer cells. BCDD inhibited cell proliferation with 48 h IC50 of 0.67 µM in HL‐60, 1 µM in Molt4, and 1.5 µM in THP1 cells. The mechanism of cell death was investigated in HL‐60 cells where it caused apoptosis by acting against several potential apoptosis suppressive targets. It inhibited phosphatidylinositol‐3‐kinase (PI3K)/AKT activity, NF‐κB, Hsp‐90, and survivin which may enhance the sensitivity of cells to apoptosis. Also, BCDD decreased the activity of Bid and Bax in cytosol, caused ΔΨmt loss, releasing pro‐apoptotic cytochrome c, SMAC/DIABLO leading to cas... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5017810 Mon, 11 Jul 2011 23:00:00 +0100 5017810 http://www.medworm.com/index.php?rid=5017809&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20673 AbstractWe provide evidence for the first time, that two natural compounds ginsenoside Rh2 (G‐Rh2) and betulinic acid (Bet A) synergistically induce apoptosis in human cervical adenocarcinoma (HeLa), human lung cancer A549, and human hepatoma HepG2 cells. G‐Rh2 and Bet A cooperated to induce Bax traslocation to mitochondria and cytochrome c release. Co‐treatment of G‐Rh2 and Bet A resulted in enhanced cleavage of caspase‐8 and Bid. Moreover, specific inhibition of caspase‐8 by siRNA technology effectively reduced caspase‐9 processing, poly (ADP‐ribose) polymerase (PARP) cleavage, caspase‐3 activation, and apoptosis in co‐treated cells, which indicated that the caspase‐8 feedback amplification pathway may have been involved in the apoptosis process. A previous study ha... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5017809 Mon, 11 Jul 2011 23:00:00 +0100 5017809 http://www.medworm.com/index.php?rid=5017808&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20678 In this study, we found that membrane type‐2 matrix metalloproteinase (MT2‐MMP), one of the matrix metalloproteinase (MMP) family members, was a novel hypoxia‐responsive gene and was upregulated by HIF‐1α under hypoxia. When cancer cells were subjected to hypoxia (1% O2) treatment, the mRNA and protein levels of MT2‐MMP were significantly increased in a time‐dependent manner in all three tested cancer cell lines including pancreatic cancer cells (PANC‐1), nonsmall cell lung cancer cells (A‐549), and cervix cancer cells (HeLa). Further analyses indicated that there were two hypoxia‐responsive elements (HREs) in the MT2‐MMP promoter, and HRE1 but not HRE2 was essential for MT2‐MMP transcriptional activation under hypoxia. HIF‐1α specifically and directly bound to MT... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5017808 Mon, 11 Jul 2011 23:00:00 +0100 5017808 http://www.medworm.com/index.php?rid=5006327&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20822 AbstractThere is growing interest in the epigenetic mechanisms that impact human health and disease, including the role of microRNAs (miRNAs). These small (18–25 nucleotide), evolutionarily conserved, non‐coding RNA molecules regulate gene expression in a post‐transcriptional manner. Several well‐orchestered regulatory mechanisms involving miRNAs have been identified, with the potential to target multiple signaling pathways dysregulated in cancer. Since the initial discovery of miRNAs, there has been progress towards therapeutic applications, and several natural and synthetic chemopreventive agents also have been evaluated as modulators of miRNA expression in different cancer types. This review summarizes the most up‐to‐date information related to miRNA biogenesis, and critical... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5006327 Thu, 07 Jul 2011 20:37:58 +0100 5006327 http://www.medworm.com/index.php?rid=5006333&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20815 AbstractDownregulation of Mig‐6 expression has been implicated in several human cancers and its loss can lead to prolonged activation of EGFR and carcinogenesis. The present study aimed to investigate the clinical significance of loss of Mig‐6 expression in nonsmall‐cell lung cancer (NSCLC) and the biological functions of Mig‐6 in NSCLC cell lines. Mig‐6 expression was downregulated in 47/91 (51.6%) cases of NSCLC that were examined. Mig‐6 downregulation significantly correlated with poor differentiation (P = 0.0131), histological type (P = 0.0021), and EGFR expression (P = 0.003). In addition, knockdown of Mig‐6 expression in H1299 and BE1 cells promoted EGF‐induced tumor cell proliferation and migration. Furthermore, Mig‐6 knockdown led to a significant incr... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5006333 Wed, 06 Jul 2011 23:00:00 +0100 5006333 http://www.medworm.com/index.php?rid=5006332&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20823 AbstractAurora A “over‐”expression may induce supernumerary centrosomes, respective multipolar mitoses, and aneuploidy. Here, we examined Aurora A positive multipolar mitoses in aneuploid, microsatellite‐stable (MSS, “CIN‐type”) versus near‐diploid, microsatellite‐instable (MSI, “MIN‐type”) colorectal carcinomas (CRC) and CRC cell lines as well as the effect of Aurora A inhibition in CRC cell lines. In situ, three‐dimensional immunofluorescence (3D‐IF) revealed Aurora A positive multipolar mitoses in both CIN‐ (n = 8) and MIN‐ (n = 10) type primary CRCs with similar frequencies (CIN: 27 ± 14%; MIN: 34 ± 14%, P = 0.224). In vitro, Aurora A positive multipolar mitoses were detected in asynchronized or thymidine synchronized CIN‐type (HT... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5006332 Wed, 06 Jul 2011 23:00:00 +0100 5006332 http://www.medworm.com/index.php?rid=5006331&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20824 This study reveals a novel layer of regulation of heparan‐binding growth factor signaling via modulation of heparan sulfate by HSulf‐2 in ccRCC. © 2011 Wiley‐Liss, Inc. (Source: Molecular Carcinogenesis) Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5006331 Wed, 06 Jul 2011 23:00:00 +0100 5006331 http://www.medworm.com/index.php?rid=5006330&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20811 In conclusion, the present study provides novel insight into the mechanism of PEITC‐induced apoptosis involving Bim. © 2011 Wiley‐Liss, Inc. (Source: Molecular Carcinogenesis) Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5006330 Wed, 06 Jul 2011 23:00:00 +0100 5006330 http://www.medworm.com/index.php?rid=5006329&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20819 AbstractTo assess systematically whether potentially functional polymorphisms in DNA repair genes influence the clinical behavior of non‐small‐cell lung cancer (NSCLC), we examined the impact of a comprehensive panel of 218 signal nucleotide polymorphisms (SNP) in 50 candidate DNA repair genes on overall survival of NSCLC in a case‐cohort of 568 lung cancer patients. SNPs associated with lung cancer prognosis primarily mapped to 14 genes in different repair pathways, and 6 SNPs were remained in the final model after multivariate stepwise Cox regression analysis: ATM rs189037; MRE11A rs11020802; ERCC2 rs1799793; MBD4 rs140693; XRCC1 rs25487, and PMS1 rs5742933. In the combined analysis of these 6 SNPs, an increasing number of unfavorable loci was associated with a poorer prognosis (P ... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5006329 Wed, 06 Jul 2011 23:00:00 +0100 5006329 http://www.medworm.com/index.php?rid=5006328&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20820 In this study, a single topical application of either 7,12‐dimethylbenz[a]anthracene (DMBA) or benzo[a]pyrene (B[a]P), alone, was found to elicit squamous cell carcinomas (SCCs) in the BK5.EP1 transgenic mice, but not in WT mice. While the epidermis of both WT and transgenic mice was hyperplastic several days after DMBA, this effect regressed in the WT mice while proliferation continued in the transgenic mice. Several parameters associated with carcinogen initiation were measured and were found to be similar between genotypes, including CYP1B1 and aromatase expression, B[a]P adduct formation, Ras activity, and keratinocyte stem cell numbers. However, EP1 transgene expression elevated COX‐2 levels in the epidermis and SCC could be completely prevented in DMBA‐treated BK5.EP1 mice eith... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=5006328 Wed, 06 Jul 2011 23:00:00 +0100 5006328 http://www.medworm.com/index.php?rid=4944225&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20809 AbstractMatrix metalloproteinase‐9 (MMP‐9) plays a central role in tumor invasion and development of metastases. Expression of MMP‐9 had been shown in human hepatocellular carcinomas (HCCs). However, it remained unclear whether MMP‐9 could influence development of HCC. In order to address this issue, we generated transgenic mice overexpressing MMP‐9 in the liver. In order to avoid embryonic lethality a Cre‐lox system was utilized for conditional overexpression of MMP‐9 under control of an albumin enhancer and promoter. Induction of MMP‐9 overexpression in transgenic mice was achieved by i.v. injection of an adenovirus coding for the Cre recombinase. Initiation of liver carcinogenesis was achieved by injection of diethylnitrosamine (DEN) followed by Phenobarbital administrat... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=4944225 Sun, 19 Jun 2011 07:34:39 +0100 4944225 http://www.medworm.com/index.php?rid=4944229&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20814 AbstractThe interrelationship between genetic susceptibility and carcinogenic exposure is important in the development of haematopoietic malignancies. Both factors need to be considered to enable assessment of disease risk associated with a given individual under certain environmental conditions. GSTT1 and GSTM1 are two genes whose proteins are involved in the detoxification of potential carcinogens. We have studied the prevalence of GSTT1 and GSTM1 null polymorphisms using a novel PCR multiplex protocol in a group of 158 patients with B‐cell lymphoma (BCL, 138 with non‐Hodgkin lymphoma and 20 with Hodgkin lymphoma) and 214 healthy controls. A questionnaire regarding occupational exposure and lifestyle factors was also completed by both groups. GSTM1 null genotype showed no significant... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=4944229 Wed, 15 Jun 2011 23:00:00 +0100 4944229 http://www.medworm.com/index.php?rid=4944228&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20817 AbstractDNA repair plays a critical role in human cancers. We hypothesized that DNA mismatch repair gene variants are associated with risk of pancreatic cancer. We retrospectively genotyped 102 single‐nucleotide polymorphisms (SNPs) of 13 mismatch repair related genes in 706 patients with pancreatic cancer and 706 cancer‐free controls using the mass spectroscopy‐based MassArray method. Association of genotype with pancreatic cancer risk was tested by multivariate logistic regression models. A significance level of P ≤ 0.0015 was set at the false discovery rate (FDR) <1% using the Beta‐Uniform Mixture method. We found 28 SNPs related to altered pancreatic cancer risk (P < 0.05). Adjusting for multiple comparisons, MGMT I143V AG/GG, PMS2 IVS1‐1121C > T TC/TT,... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=4944228 Wed, 15 Jun 2011 23:00:00 +0100 4944228 http://www.medworm.com/index.php?rid=4944227&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20818 AbstractDesmocollin 3 (DSC3) is a desmosomal cadherin that is required for maintaining cell adhesion in the epidermis as demonstrated by the intra‐epidermal blistering observed in Dsc3 null skin. Recently, it has been suggested that deregulated expression of DSC3 occurs in certain human tumor types. It is not clear whether DSC3 plays a role in the development or progression of cancers arising in stratified epithelia such as the epidermis. To address this issue, we generated a mouse model in which Dsc3 expression is ablated in K‐Ras oncogene‐induced skin tumors. Our results demonstrate that loss of Dsc3 leads to an increase in K‐Ras‐induced skin tumors. We hypothesize that acantholysis‐induced epidermal hyperplasia in the Dsc3 null epidermis facilitates Ras‐induced tumor devel... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=4944227 Wed, 15 Jun 2011 23:00:00 +0100 4944227 http://www.medworm.com/index.php?rid=4944226&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20813 This study provides evidence that although genetic loss of Brca1 and E‐cadherin are infrequent in breast cancer, they are down‐regulated at the transcriptional level by CtBP1 expression. Thus, CtBP1 activation could be a potential biomarker for breast cancer development. © 2011 Wiley‐Liss, Inc. (Source: Molecular Carcinogenesis) Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=4944226 Wed, 15 Jun 2011 23:00:00 +0100 4944226 http://www.medworm.com/index.php?rid=4944232&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20812 AbstractNimbolide, a plant‐derived limonoid has been shown to exert its antiproliferative effects in various cell lines. We demonstrate that nimbolide effectively inhibited proliferation of WiDr colon cancer cells through inhibition of cyclin A leading to S phase arrest. It also caused activation of caspase‐mediated apoptosis through the inhibition of ERK1/2 and activation of p38 and JNK1/2. Further nimbolide effectively retarded tumor cell migration and invasion through inhibition of metalloproteinase‐2/9 (MMP‐2/9) expression, both at the mRNA and protein level. It was also a strong inhibitor of VEGF expression, promoter activity, and in vitro angiogenesis. Finally, nimbolide suppressed the nuclear translocation of p65/p50 and DNA binding of NF‐κB, which is an important transcr... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=4944232 Tue, 14 Jun 2011 23:00:00 +0100 4944232 http://www.medworm.com/index.php?rid=4944231&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20807 AbstractThe role of X chromosome‐linked inhibitor of apoptosis protein (XIAP)‐associated factor 1 (XAF1) in mediating apoptosis has been reported but the underlying mechanism remains unclear. The present study was designed to examine the putative interaction between XAF1 and p53 and the functional importance of this interaction in regulation of apoptosis in human gastric and colon cancer cells. We first identified XAF1 as a novel target gene of p53 by the chromatin immunoprecipitation (CHIP) assay and demonstrated that wild‐type p53, but not mutant p53, down‐regulated XAF1 at both mRNA and protein levels, which acted mostly under the condition of high expression of XAF1 and was associated with the physical interaction between p53 and the XAF1 promoter. We also found that the over�... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=4944231 Tue, 14 Jun 2011 23:00:00 +0100 4944231 http://www.medworm.com/index.php?rid=4944230&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20810 This study reported the constitutive activation of aryl hydrocarbon receptor (AhR), leading to ABCG2 upregulation and the multidrug resistance (MDR) phenotype, in ESCC cell lines with acquired cisplatin resistance. Reporter gene assay, chromatin immunoprecipitation analysis and specific gene knockdown confirmed that the enhanced AhR binding to a xenobiotic response element (XRE) within the ABCG2 promoter is responsible for ABCG2 overexpression. A HSP90 inhibitor (17‐AAG) and two AhR antagonists (kaempferol and salicylamide) were shown to inhibit ABCG2 upregulation, thereby reversing the ABCG2‐mediated MDR. Our data therefore advocate the use of these inhibitors as novel chemosensitizers for the treatment of esophageal cancer. © 2011 Wiley‐Liss, Inc. (Source: Molecular Carcinogenesis... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=4944230 Tue, 14 Jun 2011 23:00:00 +0100 4944230 http://www.medworm.com/index.php?rid=4910371&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20808 AbstractSEL1L is a putative tumor suppressor gene that is frequently down‐regulated in pancreatic ductal adenocarcinoma (PDA). A single‐nucleotide polymorphism (SNP) rs12435998 in intron3 of SEL1L has previously been reported to be associated with susceptibility to Alzheimer's disease. We hypothesized that this SNP may influence clinical outcomes of patients with PDA. We analyzed DNA samples from 497 Caucasian patients with pathologically confirmed primary PDA. Of these, 98 had been enrolled in a clinical trial of neoadjuvant chemo‐radiotherapy and 77 of the 98 had subsequently undergone pancreaticoduodenectomy (PD). We performed Kaplan–Meier analysis to evaluate the correlation between different SNP genotypes and age at diagnosis, survival time after diagnosis, and survival time a... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=4910371 Wed, 08 Jun 2011 23:09:01 +0100 4910371 http://www.medworm.com/index.php?rid=4910375&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20803 AbstractAs a component of the MRN (MRE11/RAD50/NBS1) complex, NBS1 plays an important role in cellular response to DNA damage and the maintenance of chromosomal integrity. The NBS1 E185Q polymorphism (8360G>C, rs1805794) has been frequently studied in some cancers with discordant results, but its association with nasopharyngeal carcinoma (NPC) in Chinese population has not been investigated. Moreover, there is no report about the association between NBS1 3′UTR variant rs2735383 and the risk of NPC. A multiple center case–control analysis was performed to assess the association between NBS1 polymorphisms and NPC risk in Eastern and Southern Chinese population. The genotypes and haplotypes were determined in 1052 cases and 1168 controls and the associations with risk of NPC were estim... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=4910375 Mon, 06 Jun 2011 23:00:00 +0100 4910375 http://www.medworm.com/index.php?rid=4910374&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20804 AbstractThere is growing evidence that cancer of the ascending (right‐side) colon is different from cancer of the descending (left‐side) colon at the molecular level. Using microarray data from 102 right‐side colon carcinomas and 95 left‐side colon carcinomas we show that different pathways dominate progression to relapse in right‐side and left‐side colon cancer. Right‐side tumors at a high risk for relapse exhibit elevated expression of cell cycle control genes and elevated Wnt signaling. On the other hand, relapse‐prone left‐side tumors show elevated expression of genes that promote stromal expansion and reduced expression of tumor suppressor genes that initiate Wnt signaling. Single gene prognostic biomarkers are found separately for right‐side and left‐side diseas... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=4910374 Mon, 06 Jun 2011 23:00:00 +0100 4910374 http://www.medworm.com/index.php?rid=4910373&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20805 AbstractHuman fibroblast growth factor receptor 4 (FGFR4) polymorphisms have recently been shown to be associated with tumor progression of various types of cancer, including cancer of the breast, colon, and prostate and sarcoma. However, their association with hepatocellular carcinoma (HCC) is unknown. We evaluated the association of FGFR4 polymorphisms with risk of HCC in a study population with HCC and with/without hepatitis B virus (HBV) infection in East China. We genotyped four FGFR4 SNPs (rs351855, rs641101, rs376618, and rs31777) in 1,451 Chinese subjects, including 711 patients with HCC, 368 controls with HBV infection and 372 controls without HBV infection, using the TaqMan genotyping assay. Unconditional logistic regression analysis was performed to evaluate associations of geno... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=4910373 Mon, 06 Jun 2011 23:00:00 +0100 4910373 http://www.medworm.com/index.php?rid=4910372&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20806 AbstractBoth p53 tumor suppressor and murine double minute 2 (MDM2) oncoprotein are crucial in carcinogenesis. We hypothesized that MDM2 promoter single nucleotide polymorphisms (SNPs) SNP309 T > G, A2164G, and p53 codon 72 are associated with risk and age at onset of squamous cell carcinoma of head and neck (SCCHN). We genotyped these SNPs in a study of 1,083 Caucasian SCCHN cases and 1,090 cancer‐free controls. Although none of these SNPs individually had a significant effect on risk of SCCHN, nor did their combined putative risk genotypes (i.e., MDM2 SNP309 GT + GG, 2164 AA, and p53 codon 72 CC), we found that individuals with two to three risk genotypes had significantly increased risk of non‐oropharyngeal cancer (OR = 1.42; 95% CI = 1.07–1.88). This increased ... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=4910372 Mon, 06 Jun 2011 23:00:00 +0100 4910372 http://www.medworm.com/index.php?rid=4839664&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20801 This study indicates that CCND1 rs9344 polymorphisms confer host susceptibility to cervical cancer. A allele possesses a relative protective effect probably through the cyclin D1b's inhibition on HPV carcinogenesis. © 2011 Wiley‐Liss, Inc. (Source: Molecular Carcinogenesis) Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=4839664 Thu, 19 May 2011 19:57:23 +0100 4839664 http://www.medworm.com/index.php?rid=4839666&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20802 AbstractEpithelial–mesenchymal transition (EMT), which involves the persistent loss of epithelial markers and expression of mesenchymal markers, is assumed to have a critical role in not only tissue development during embryogenesis but also central mechanisms that enhance the invasive and metastatic ability of cancer cells. Twist has been identified to play an essential role in EMT‐mediated tumor invasion and metastasis. Although recent studies suggest that twist expression levels in tissue specimens of lung cancer might be associated with prognosis, the expression of twist in lung cancer cells itself and its effect have not been fully evaluated. Here, we evaluated twist expression and its effect on phenotype alteration in lung cancer cell lines. Twist expression varied among human lun... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=4839666 Tue, 17 May 2011 23:00:00 +0100 4839666 http://www.medworm.com/index.php?rid=4839665&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20787 In this study, we investigated the anticancer effects of a new benzimidazole derivative, 2‐(furanyl)‐5‐(piperidinyl)‐ (3,4,5‐trimethoxybenzyl) benzimidazole (FPipTB) in human chondrosarcoma cells. FPipTB‐induced apoptosis in human chondrosarcoma cell lines (JJ012 and SW1353) but not in primary chondrocytes. Furthermore, it triggered endoplasmic reticulum (ER) stress, which was characterized by changes in cytosolic calcium levels. Treatment of chondrosarcoma cells with FPipTB was associated with increased intracellular levels of ASK1, p38, p53, and Bax, followed by release of cytochrome c from mitochondria and activation of caspases. It is also known that ER stress activates apoptosis signal‐regulating kinase 1 (ASK1), which mediates activation of JNK and p38 pathways. We also... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=4839665 Tue, 17 May 2011 23:00:00 +0100 4839665 http://www.medworm.com/index.php?rid=4819655&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20764 AbstractObesity and its associated metabolic syndrome (MetS) are recognized risk factors for breast cancer. The molecular basis for this association remains largely unknown. Adipokines, in particular leptin and adiponectin, are thought to form part of the mechanism linking obesity with cancer through their altered expression/production either systemically (endocrine pathway) or locally (paracrine/autocrine pathway). Using quantitative PCR, mRNA expression of adiponectin (AdipoQ) and leptin (Ob) in mammary adipose tissue (MAT), intratumoral leptin and associated ligand receptors (ObR, AdipoR1, and AdipoR2) was examined in 77 patients with complete anthropomorphic and serological data. Expression of Ob in MAT, and ObR in matched tumor tissue was significantly higher in patients with MetS com... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=4819655 Fri, 13 May 2011 21:22:28 +0100 4819655 http://www.medworm.com/index.php?rid=4819656&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20756 In conclusion, silibinin inhibits the invasion and migration of 786‐O cells in vitro, inhibits the growth of xenografts in vivo, and enhances chemosensitivity to 5‐fluorouracil and paclitaxel. © 2011 Wiley‐Liss, Inc. (Source: Molecular Carcinogenesis) Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=4819656 Thu, 12 May 2011 23:00:00 +0100 4819656 http://www.medworm.com/index.php?rid=4811945&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20800 AbstractTerbinafine (TB), an oral antifungal agent used in the treatment of superficial mycosis, has been reported to exert an anti‐tumor effect in various cancer cells. However, the effect of TB on oral cancer has not been evaluated. Herein we demonstrate that TB (0–60 µM) concentration‐dependently decreased cell number in cultured human oral squamous cell carcinoma (OSCC), KB cells. The anti‐proliferation effect of TB was also observed in two other OSCC cell lines, SAS and SCC 15. TB (60 µM) was not cytotoxic and its inhibition on KB cell growth was reversible. [3H]thymidine incorporation and flow cytometric analyses revealed that TB‐inhibited DNA synthesis and induced the G0/G1 cell‐cycle arrest. The TB‐induced cell‐cycle arrest occurred when the cyclin‐dependent... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=4811945 Thu, 12 May 2011 05:10:40 +0100 4811945 http://www.medworm.com/index.php?rid=4811946&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20798 AbstractAberrant promoter methylation of specific genes and infection with human papillomavirus 16 (HPV16) are known risk factors for the development of Head and Neck Squamous Cell Carcinoma (HNSCC). Little knowledge exists on the interaction of HPV16 infection and promoter methylation in HNSCC. The promoter methylation status of 12 genes (TIMP3, CDH1, CDKN2A, DAPK1, transcription factor 21 (TCF21), CD44, MLH1, MGMT, RASSF1, cyclin A1 (CCNA1), LARS2, and CEBPA) was evaluated by methylation‐specific polymerase chain reaction in 55 primary HNSCC and 31 controls. The results were correlated with HPV16 status and clinicopathological characteristics. CCNA1 and p53 protein expression were additionally determined by immunohistochemistry and compared with p53 mutation status. Methylation of DAPK... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=4811946 Tue, 10 May 2011 23:00:00 +0100 4811946 http://www.medworm.com/index.php?rid=4794190&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20789 In this study, oroxylin A showed strong reversal potency in BEL7402/5‐FU cells and the reversal fold (RF) reached 4.69. Simultaneously, rhodamine‐123 accumulation assay and flow cytometry analysis demonstrated oroxylin A could increase drug accumulation. When combined with oroxylin A, 5‐FU showed inducing apoptosis effect more seriously in DAPI staining experiment. Moreover, the mRNA and protein expression of multi‐drug resistance gene (MDR1) were also decreased by oroxylin A. Further experiments exhibited that oroxylin A can downregulate P‐gp expression through inhibiting nuclear factor‐κB (NF‐κB) signaling pathway, which might be the mechanism of reversal resistance of oroxylin A. In summary, oroxylin A could be a good candidate for the development of new MDR reversal age... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=4794190 Thu, 05 May 2011 23:00:00 +0100 4794190 http://www.medworm.com/index.php?rid=4794189&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20783 AbstractHere, we have demonstrated that xenobiotic activation of the nuclear receptor (CAR, NR1I3) can result in arresting DNA‐damaged human hepatocellular carcinoma Huh7 cells at the G2/M phase. Huh7 cells over‐expressing CAR were either treated with dimethyl sulfoxide, the CAR activator TCPOBOP (1,4‐bis[2‐(3,5‐dichloropyridyloxy)]benzene; androstenol, 16,(5α)‐androsten‐3α‐OL), or repressor androstenol; these treatments were then followed by adriamycin treatment to damage DNA. FACS analysis revealed that CAR‐activation by TCPOBOP increased the rate of arrested Huh7 cells at the G2/M phase (4N DNA content) after DNA damage by adriamycin. This increase correlated with the increase of cell viability in TCPOBOP‐treated Huh7 cells, as determined by MTT assays. Real‐time... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=4794189 Thu, 05 May 2011 23:00:00 +0100 4794189 http://www.medworm.com/index.php?rid=4794188&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20795 AbstractThe p53 tumor suppressor protein performs a number of cellular functions, ranging from the induction of cell cycle arrest and apoptosis to effects on DNA repair. Modulating p53 activity with Mdm2 inhibitors is a promising approach for treating cancer; however, it is presently unclear how the in vivo application of Mdm2 inhibitors impact the myriad processes orchestrated by p53. Since approximately half of all colon cancers (predominately cancers with microsatellite instability) are p53‐normal, we assessed the anticancer activity of the Mdm2 inhibitor Nutlin‐3 in the mouse azoxymethane (AOM) colon cancer model, in which p53 remains wild type. Using a cell line derived from an AOM‐induced tumor, we found that four daily exposures to Nutlin‐3 induced persistent p53 stabilizati... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=4794188 Thu, 05 May 2011 23:00:00 +0100 4794188 http://www.medworm.com/index.php?rid=4794187&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20797 In this study, we investigated the loss of heterozygosity (LOH) incidence that target FHIT genomic structure and chromosome 3p in cancerous and pre‐neoplastic lesions of Egyptian breast patients. Genomic DNA was isolated from tumor tissues and their normal counterparts of 55 Egyptian patients diagnosed with breast cancer and 11 patients diagnosed with preneoplastic breast lesions. LOH was detected in 51% of breast cancer cases in at least one microsatellite marker of the four investigated markers. While, none of the markers showed LOH among the pre‐neoplastic breast lesions. We also observed a significant association between LOH and invasive ductal carcinoma (IDC) histopathological type while no association observed between LOH and patients' age, tumor grade, or lymph node involvement.... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=4794187 Thu, 05 May 2011 23:00:00 +0100 4794187 http://www.medworm.com/index.php?rid=4774768&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20784 This study aimed to evaluate the relationship between genetic variants in COX‐2 promoter interacting with Helicobacter pylori and the susceptibility to gastric cancer (GC). Three COX‐2 polymorphisms −1290A>G (rs689465), −1195G>A (rs689466), and −765G>C (rs20417) were genotyped in 323 GC patients and 944 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression model. In GC patients, the ORs were 2.33 (95% CI = 1.50–3.63) and 2.70 (95% CI = 1.68–4.33) for −1195AA and −765CG genotype carriers, respectively. Haplotype analysis showed all −1195A allele‐containing haplotypes, except G−1290–A−1195–G−765, were associated with increased risk for GC, compared with the A−1290–G−1195–G−765 haplotype... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=4774768 Sun, 01 May 2011 23:00:00 +0100 4774768 http://www.medworm.com/index.php?rid=4774767&cid=s_33604_67_f&fid=33604&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fmc.20788 AbstractNeocarzinostatin (NCS), a potent mutagen and carcinogen, consists of an enediyne prodrug and a protein carrier. It has a unique double role in that it intercalates into DNA and imposes radical‐mediated damage after thiol activation. Here we employed NCS as a probe to examine the DNA‐protection capability of caffeine, one of common dietary phytochemicals with potential cancer‐chemopreventive activity. NCS at the nanomolar concentration range could induce significant single‐ and double‐strand lesions in DNA, but up to 75 ± 5% of such lesions were found to be efficiently inhibited by caffeine. The percentage of inhibition was caffeine‐concentration dependent, but was not sensitive to the DNA‐lesion types. The well‐characterized activation reactions of NCS allowed ... Molecular Carcinogenesis journals http://www.medworm.com/rss/comments.php?id=4774767 Sun, 01 May 2011 23:00:00 +0100 4774767