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Ján Remšík, Lucia Binó, Zuzana Kahounová, Gvantsa Kharaishvili, Šárka Šimecková, Radek Fedr, Tereza Kucírková, Sára Lenárt, Ximena Maria Muresan, Eva Slabáková, Lucia Knopfová, Jan Bouchal, Milan Král, Petr Beneš, Karel Soucek
The cell surface glycoprotein Trop-2 is commonly overexpressed in carcinomas and represents an exceptional antigen for targeted therapy. Here, we provide evidence that surface Trop-2 expression is functionally connected with an epithelial phenotype in breast and prostate cell lines and in patient tumor samples. We further show that Trop-2 expression is suppressed epigenetically or through the action of epithelial-to-mesenchymal transition transcription factors and that deregulation of Trop-2 expression is linked with cancer progression and poor patient prognosis...
July 16, 2018: Carcinogenesis
Surendra R Punganuru, Hanumantharao Madala, Viswanath Arutla, Kalkunte S Srivenugopal
The molecular basis of anticancer and apoptotic effects of R-goniothalamin (GON), a plant secondary metabolite was studied. We show that induction of oxidative stress and reactivation of mutant p53 underlie the strong cytotoxic effects of GON against the breast cancer cells. While GON was not toxic to the MCF10a breast epithelial cells, the SKBR3 breast cancer cells harboring an R175H mutant p53 were highly sensitive (IC50 = 7.3 µM). Flow cytometry and other pertinent assays showed that GON induced abundant reactive oxygen species (ROS), glutathione depletion, protein glutathionylation and activation of apoptotic markers...
July 13, 2018: Carcinogenesis
Chengsen Chai, Hong Wu, Benfan Wang, David D Eisenstat, Roger P Leng
Triple negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis and high mortality rate. The tumor suppressor PTEN plays an important role in cell proliferation and cell migration by negatively regulating the PI3K/Akt pathway. PTEN is down-regulated by microRNAs in multiple cancers. However, few microRNAs have been reported to directly target PTEN in TNBC. In this study, microRNAs predicted to target PTEN were screened by using immunoblotting and luciferase reporter assays. Expression levels of microRNA-498 (miR-498) were measured by TaqMan microRNA assays...
July 7, 2018: Carcinogenesis
Naveen Kumar, Peeyush Prasad, Eshna Jash, Smruthi Jayasundar, Itender Singh, Neyaz Alam, Nabendu Murmu, S P Somashekhar, Aaron Goldman, Seema Sehrawat
Breast cancer is a leading cause of cancer-related mortality in women. Triple-negative breast cancer (TNBC; HER2-, ER-/PR-) is an aggressive subtype prone to drug resistance and metastasis, which is characterized by high intratumor microvascular density (iMVD) resulting from angiogenesis. However, the mechanisms contributing to the aggressive phenotypes of TNBC remain elusive. We recently reported that down-regulation of exchange factor directly activated by Cyclic AMP (cAMP), also known as EPAC1, leads to a reduction in metastatic properties including proliferation and cell migration in TNBC cell lines...
July 5, 2018: Carcinogenesis
Weixing Dai, Yang Feng, Shaobo Mo, Wenqiang Xiang, Qingguo Li, Renjie Wang, Ye Xu, Guoxiang Cai
The purpose of our study was to develop a multigene signature based on transcriptome profiles of both mRNAs and lncRNAs to identify a group of patients who are at high risk of early relapse in stage II-III colon cancer. Firstly, propensity score matching was conducted between patients in early relapse group and long-term survival group from GSE39582 training series (N=359) and patients were matched 1:1. Global transcriptome analysis was then performed between the paired groups to identify tumor specific mRNAs and lncRNAs...
July 5, 2018: Carcinogenesis
Genevieve E Melling, Sarah E Flannery, Siti A Abidin, Hannah Clemmens, Priyanka Prajapati, Emma E Hinsley, Stuart Hunt, James W F Catto, Ricardo Della Coletta, Massimiliano Mellone, Gareth J Thomas, E Ken Parkinson, Stephen S Prime, Ian C Paterson, David J Buttle, Daniel W Lambert
No abstract text is available yet for this article.
July 4, 2018: Carcinogenesis
Julie E Goodman, Heather N Lynch, Lorenz R Rhomberg
No abstract text is available yet for this article.
July 3, 2018: Carcinogenesis
Kathryn Z Guyton, Ivan Rusyn, Weihsueh A Chiu, Denis E Corpet, Martin van den Berg, Matthew K Ross, David C Christiani, Frederick A Beland, Martyn T Smith
No abstract text is available yet for this article.
July 3, 2018: Carcinogenesis
Chiara Porta, Arianna Marino, Francesca Maria Consonni, Augusto Bleve, Silvia Mola, Mariangela Storto, Elena Riboldi, Antonio Sica
New evidences indicate that the metabolic instruction of immunity (immune metabolism) results from the integration of cell metabolism and whole body metabolism, that are both influenced by nutrition, microbioma metabolites and disease-driven metabolism (e.g. cancer metabolism). Cancer metabolism influences the immunological homeostasis and promotes immune alterations that support disease progression, hence influencing the clinical outcome. Cancer cells display increased glucose uptake and fermentation of glucose to lactate, even in the presence of completely functioning mitochondria...
July 2, 2018: Carcinogenesis
Tommaso A Dragani, Francesca Colombo, Elizabeth N Pavlisko, Victor L Roggli
Asbestos exposure is the main etiology of malignant mesothelioma, but there are conflicting data on whether the intensity of exposure modulates the development of this disease. This study considered 594 patients with malignant mesothelioma for whom count data on asbestos bodies and fibers (per gram of wet lung tissue) were available. The relationships between age at diagnosis (a time-to-event outcome variable) and these two measures of internal asbestos exposure, along with other possible modulating factors (sex, tumor location, histological subtype, and childhood exposure), were assessed on multivariable Cox proportional hazard models, stratifying by decade of birth year...
June 30, 2018: Carcinogenesis
Susanna Larsson, Anna Wenger, Sándor Dósa, Magnus Sabel, Teresia Kling, Helena Carén
The leading cause of cancer-related mortality among children is brain tumours, and glioblastoma multiforme (GBM) has the worst prognosis. New treatments are urgently needed, but with few cases and clinical trials in children, pre-clinical models such as patient-derived tumour xenografts (PDTX) are important. To generate these, tumour tissue is transplanted into mice, but this yields highly variable results and requires serial passaging in mice, which is time-consuming and expensive. We therefore aimed to establish a cell line-based orthotopic mouse model representative of the patient tumour...
June 30, 2018: Carcinogenesis
Anastasios Gkountakos, Sara Pilotto, Andrea Mafficini, Caterina Vicentini, Michele Simbolo, Michele Milella, Giampaolo Tortora, Aldo Scarpa, Emilio Bria, Vincenzo Corbo
Genomic alterations affecting components of the mechanistic target of rapamycin (mTOR) pathway are found rather frequently in cancers, suggesting that aberrant pathway activity is implicated in oncogenesis of different tumor types. mTOR functions as the core catalytic kinase of two distinct complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2), which control numerous vital cellular processes. There is growing evidence indicating that Rictor, an essential subunit of the mTORC2 complex, is inappropriately overexpressed across numerous cancer types and this is associated with poor survival...
June 28, 2018: Carcinogenesis
Maria Grazia Mascolo, Stefania Perdichizzi, Monica Vaccari, Francesca Rotondo, Cristina Zanzi, Sandro Grilli, Martin Paparella, Miriam N Jacobs, Annamaria Colacci
No abstract text is available yet for this article.
June 27, 2018: Carcinogenesis
Yu-Chen Yang, Wei-Ping Fu, Jing Zhang, Li Zhong, Shao-Xi Cai, Chang Sun
Lung cancer is a common cancer in human and has presented significant genetic predisposition. Previous genome-wide association study observed that rs401681 within CLPTM1L (CLPTM1 like) was significantly associated with lung cancer. By analyzing 1000 genomes data for East Asian, we identified only one SNP in nearby region, rs402710, in high linkage disequilibrium with rs401681, which was also associated with lung cancer. However, the real causal SNP and mechanism for the association was still not clear. The following plasmid construction, mutagenesis, transient transfection and luciferase reading indicated that both SNPs could regulate gene expression in lung/bronchial epithelium Beas-2B cell line...
June 23, 2018: Carcinogenesis
Isabelle R Miousse, Julia Tobacyk, Charles M Quick, Azemat Jamshidi-Parsian, Charles M Skinner, Rajshekhar Kore, Stepan B Melnyk, Kristy R Kutanzi, Fen Xia, Robert J Griffin, Igor Koturbash
Methionine dependency describes the characteristic rapid in vitro death of most tumor cells in the absence of methionine. Combining chemotherapy with dietary methionine deprivation (MDD) at tolerable levels has vast potential in tumor treatment; however, it is limited by MDD-induced toxicity during extended deprivation. Recent advances in imaging and irradiation delivery have created the field of stereotactic body radiotherapy (SBRT), where fewer large-dose fractions delivered in less time result in increased local-tumor control, which could be maximally synergistic with an MDD short course...
June 23, 2018: Carcinogenesis
Yeo Jin Kim, Young Ju Lee, Hyo Jeong Kim, Hyun Soo Kim, Mi-Sun Kang, Sung-Keun Lee, Moo Kyun Park, Kazuyoshi Murata, Hye Lim Kim, Young Rok Seo
Nickel is a major carcinogen that is implicated in tumor development through occupational and environmental exposure. Although the exact molecular mechanisms of carcinogenesis by low-level nickel remain unclear, inhibition of DNA repair is frequently considered to be a critical mechanism of carcinogenesis. Here, we investigated whether low concentrations of nickel would affect p53-mediated DNA repair, especially nucleotide excision repair. Our results showed that nickel inhibited the promoter binding activity of p53 on the downstream gene GADD45A, as a result of the disturbance of p53 oligomerization by nickel...
June 19, 2018: Carcinogenesis
Jinyoung Byun, Ann G Schwartz, Christine Lusk, Angela S Wenzlaff, Mariza de Andrade, Diptasri Mandal, Colette Gaba, Ping Yang, Ming You, Elena Y Kupert, Marshall W Anderson, Younghun Han, Yafang Li, David Qian, Adrienne Stilp, Cathy Laurie, Sarah Nelson, Wenying Zheng, Rayjean J Hung, Valerie Gaborieau, James Mckay, Paul Brennan, Neil E Caporaso, Maria Teresa Landi, Xifeng Wu, John R McLaughlin, Yonathan Brhane, Yohan Bossé, Susan M Pinney, Joan E Bailey-Wilson, Christopher I Amos
To identify genetic variation associated with lung cancer risk, we performed a genome-wide association analysis of 685 lung cancer cases that had a family history of two or more first or second degree relatives compared with 744 controls without lung cancer that were genotyped on an Illumina Human OmniExpressExome-8v1 array. To ensure robust results, we further evaluated these findings using data from six additional studies that were assembled through the Transdisciplinary Research on Cancer of the Lung Consortium comprising 1,993 familial cases and 33,690 controls...
June 19, 2018: Carcinogenesis
Jyoti Goad, Yi-An Ko, Manish Kumar, M Fairuz B Jamaluddin, Pradeep S Tanwar
Unopposed oestrogen results in approximately 80% of all the endometrial cancer patients. The relationship between unopposed oestrogen and endometrial cancer was indicated by the increase in the number of endometrial cancer cases due to the widespread use of oestrogen replacement therapy. Approximately 30% of the endometrial cancer patients have mutations in the Wnt signalling pathway. How the unbalanced ratios of ovarian hormones and the mutations in Wnt signalling pathway interact to cause endometrial cancer is currently unclear...
June 15, 2018: Carcinogenesis
Jessica I Grill, Jens Neumann, Andrea Ofner, Maximilian K Marschall, Heike Zierahn, Andreas Herbst, Eckhard Wolf, Frank T Kolligs
Colorectal carcinogenesis is a progressive multistep process involving the sequential accumulation of genetic alterations in tumor suppressor genes and oncogenes. Down regulated by oncogenes 1 (Dro1/Ccdc80) has been shown to be a potent tumor suppressor of colorectal carcinogenesis in the genetic ApcMin/+ mouse model. In ApcMin/+ mice loss of DRO1 strongly increases colonic tumor multiplicity and leads to the regular formation of adenocarcinoma in the colon. To investigate DRO1`s role in chemically induced as well as inflammation-associated colorectal carcinogenesis the effect of Dro1 inactivation was studied in mice subjected to the carcinogen azoxymethane (AOM) and upon combined treatment with AOM and the proinflammatory agent dextran sodium sulfate (DSS), respectively...
June 13, 2018: Carcinogenesis
Mateus Mota, William P Jackson, Sarah K Bailey, Praveen Vayalil, Aimee Landar, Jack W Rostas, Madhuri S Mulekar, Rajeev S Samant, Lalita A Shevde
The NF2 gene encodes the tumor and metastasis suppressor protein Merlin. Merlin exerts its tumor suppressive role by inhibiting proliferation and inducing contact-growth inhibition and apoptosis. In the current investigation, we determined that loss of Merlin in breast cancer tissues is concordant with the loss of the inhibitory SMAD, SMAD7, of the TGF-β pathway. This was reflected as dysregulated activation of TGF-β signaling that co-operatively engaged with effectors of the Hippo pathway (YAP/TAZ/TEAD)...
June 9, 2018: Carcinogenesis
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