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Maria Grazia Mascolo, Stefania Perdichizzi, Monica Vaccari, Francesca Rotondo, Cristina Zanzi, Sandro Grilli, Martin Paparella, Miriam N Jacobs, Annamaria Colacci
The development of alternative methods to animal testing is a priority in the context of regulatory toxicology. Carcinogenesis is a field where the demand for alternative methods is particularly high. The standard rodent carcinogenicity bioassay requires a large use of animals, high costs, prolonged duration, and shows several limitations, which can affect the comprehension of the human relevance of animal carcinogenesis. The Cell Transformation Assay has long been debated as a possible in vitro test to study carcinogenesis...
March 15, 2018: Carcinogenesis
Bríd M Ryan
Compared with all other racial and ethnic groups in the U.S., African Americans are disproportionally affected by lung cancer, both in terms of incidence and survival. It is likely that smoking, as the main etiological factor associated with lung cancer, contributes to these disparities, but the precise mechanism is still unclear. This paper seeks to explore the history of lung cancer disparities and review to the literature regarding the various factors that contribute to them.
March 14, 2018: Carcinogenesis
Yue Guo, Renyi Wu, John M Gaspar, Davit Sargsyan, Zheng-Yuan Su, Chengyue Zhang, Linbo Gao, David Cheng, Wenji Li, Chao Wang, Ran Yin, Mingzhu Fang, Michael P Verzi, Ronald P Hart, Ah-Ng Kong
Inflammation is highly associated with colon carcinogenesis. Epigenetic mechanisms could play an important role in the initiation and progression of colon cancer. Curcumin, a dietary phytochemical, shows promising effects in suppressing colitis-associated colon cancer in AOM-DSS mice. However, the potential epigenetic mechanisms of curcumin in colon cancer remain unknown. In this study, the anti-cancer effect of curcumin in suppressing colon cancer in an 18-week AOM-DSS colon cancer mouse model was confirmed...
March 14, 2018: Carcinogenesis
Xiangfeng Wang, Hu Fang, Yong Cheng, Lin Li, Xiaohui Sun, Tao Fu, Peide Huang, Anping Zhang, Zhimin Feng, Chunxue Li, Xuanlin Huang, Guangyan Li, Peina Du, Huanming Yang, Xiaodong Fang, Fan Li, Qiang Gao, Baohua Liu
Synchronous colorectal cancers (syCRCs), which present two or more lesions at diagnosis, are rare and pose a great challenge for clinical management. Although some predisposing factors associated with syCRCs have been studied with limited accession, the full repertoire of genomic events among the lesions within an individual and the causes of syCRCs remain unclear. We performed whole-exome sequencing of 40 surgical tumour samples of paired lesions from 20 patients to characterize the genetic alterations. Lesions from same patient showed distinct landscapes of somatic aberrations and shared few mutations, which suggests that they originate and develop independently although they shared the similar genetic background...
March 13, 2018: Carcinogenesis
Yanlan Li, Xiaodan Liu, Pengchao Gong, Xin Tian
Bufalin, a key active ingredient of the Chinese medicine Chan Su, inhibits breast cancer tumorigenesis in vitro and in vivo. Here we found that the pan-caspase inhibitor zVAD-fmk failed to inhibit bufalin-induced cell death in MCF-7 and MDA-MB-231 human breast cancer cells, confirming that the cell death induced by bufalin is caspase-independent. Instead, bufalin increased the expression of the necroptosis mediators RIP1 and RIP3. Bufalin-induced cell death was prevented by small molecule inhibitors of RIP1 and poly (ADP-ribose) polymerase-1 (PARP-1) or genetic knockdown of RIP3 by shRNA transfection...
March 13, 2018: Carcinogenesis
Hidejiro Torigoe, Hiromasa Yamamoto, Masakiyo Sakaguchi, Chen Youyi, Kei Namba, Hiroki Sato, Kazuhiko Shien, Junichi Soh, Ken Suzawa, Shuta Tomida, Kazunori Tsukuda, Shinichiro Miyoshi, Shinichi Toyooka
Epidermal growth factor receptor (EGFR) is a member of the ErbB (HER) family that is known to play important roles in the pathogenesis of various human cancers. Mutations of the EGFR gene are commonly found as oncogenic driver mutations, and have been targeted for treatment in non-small cell lung cancer (NSCLC). Leucine-rich repeat and immunoglobulin-like domain protein-1 (LRIG1) is a cell-surface protein that is known as a negative regulator of the ErbB (HER) family. In this study, we first confirmed that the expression levels of LRIG1 were much lower in NSCLC than in non-malignant cells or tissues...
March 13, 2018: Carcinogenesis
Laura Rosenberg, Charles H Yoon, Gaurav Sharma, Monica M Bertagnolli, Nancy L Cho
Desmoid tumors (DTs) are unusual neoplasms of mesenchymal origin that exhibit locally invasive behavior. Surgical resection is the initial treatment of choice for DTs. For patients with recurrent or unresectable disease, however, medical options are limited. Sorafenib is a multikinase inhibitor with known anti-tumor activity in various cancers via suppression of the PI3K/Akt/mTOR pathway. Here, we examined the effects of sorafenib on patient-derived DT cell lines, with the aim of characterizing the efficacy and molecular mechanism of action...
March 10, 2018: Carcinogenesis
Xuyao Zhang, Wei Chen, Jiajun Fan, Shaofei Wang, Zongshu Xian, Jingyun Luan, Yubin Li, Yichen Wang, Yanyang Nan, Man Luo, Song Li, Wenzhi Tian, Dianwen Ju
CD47-targeting immune checkpoint inhibitors have been investigated for immunotherapy of several cancers, glioblastoma, one of the most common tumors in brain, was still a challenge for CD47-targeting therapy. Herein, we reported novel strategies for glioblastoma therapy via blocking CD47-SIRPα by SIRPα-Fc alone or in combination with autophagy inhibition. Our results showed that SIRPα-Fc increased macrophages-triggered cytotoxicity and phagocytosis of glioblastoma cells then elicited potent anti-tumor efficacy...
March 10, 2018: Carcinogenesis
Hasmik Grigoryan, William M B Edmands, Qing Lan, Henrik Carlsson, Roel Vermeulen, Luoping Zhang, Song-Nian Yin, Gui-Lan Li, Martyn T Smith, Nathaniel Rothman, Stephen M Rappaport
Although benzene has long been recognized as a cause of human leukemia, the mechanism by which this simple molecule causes cancer has been problematic. A complicating factor is benzene metabolism, which produces many reactive intermediates, some specific to benzene and others derived from redox processes. Using archived serum from 20 nonsmoking Chinese workers, 10 with and 10 without occupational exposure to benzene (exposed: 3.2 - 88.9 ppm, controls: 0.002 - 0.020 ppm), we employed an adductomic pipeline to characterize protein modifications at Cys34 of human serum albumin (HSA), a nucleophilic hotspot in extracellular fluids...
March 10, 2018: Carcinogenesis
G E Melling, S E Flannery, S A Abidin, H Clemmens, P Prajapati, E E Hinsley, S Hunt, J W F Catto, R D Coletta, M Mellone, G J Thomas, E K Parkinson, S S Prime, I C Paterson, D J Buttle, D W Lambert
The dissemination of cancer cells to local and distant sites depends on a complex and poorly understood interplay between malignant cells and the cellular and non-cellular components surrounding them, collectively termed the tumour microenvironment. One of the most abundant cell types of the tumour microenvironment is the fibroblast, which becomes corrupted by locally derived cues such as TGF-β1 and acquires an altered, heterogeneous phenotype (cancer-associated fibroblast, CAF) supportive of tumour cell invasion and metastasis...
February 28, 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
Smith et al. (Env. Health Perspect. 124: 713, 2016) identified 10 key characteristics (KCs), one or more of which are commonly exhibited by established human carcinogens. The KCs reflect the properties of a cancer-causing agent, such as 'is genotoxic,' 'is immunosuppressive' or 'modulates receptor-mediated effects,' and are distinct from the hallmarks of cancer, which are the properties of tumors. To assess feasibility and limitations of applying the KCs to diverse agents, methods and results of mechanistic data evaluations were compiled from eight recent IARC Monograph meetings...
February 21, 2018: Carcinogenesis
Bethtrice Elliott, DeAdra L Zackery, Vanessa A Eaton, Re'Josef T Jones, Fisseha Abebe, Camille C Ragin, Shafiq A Khan
Epidemiological studies show that the incidence and mortality rates of prostate cancer (PCa) are significantly higher in African-American (AA) men when compared to Caucasian (CA) men in the US. Transforming growth factor β (TGFβ) signaling pathway is linked to health disparities in African-Americans. Recent studies suggest a role of TGFβ3 in cancer metastases and its effect on the migratory and invasive behavior; however, its role in prostate cancer in African American men has not been studied. We determined the circulating levels of TGFβ3 in AA and CA men diagnosed with PCa using ELISA...
February 21, 2018: Carcinogenesis
Chizu Tanikawa, Yoichiro Kamatani, Atsushi Takahashi, Yukihide Momozawa, Karine Leveque, Satoshi Nagayama, Koshi Mimori, Masaki Mori, Hideshi Ishii, Johji Inazawa, Jun Yasuda, Akito Tsuboi, Atsushi Shimizu, Makoto Sasaki, Taiki Yamaji, Norie Sawada, Motoki Iwasaki, Shoichiro Tsugane, Mariko Naito, Kenji Wakai, Teruhide Koyama, Toshiro Takezaki, Koichiro Yuji, Yoshinori Murakami, Yusuke Nakamura, Michiaki Kubo, Koichi Matsuda
Colorectal cancer is the fourth leading cause of cancer mortality worldwide. Genome-wide association studies (GWAS) identified more than 50 colorectal cancer loci. However, most of the previous studies were conducted in European populations, and host genetic factors among Japanese population are largely remained to be identified. To identify novel loci in the Japanese population, here, we performed a large-scale GWAS using 6,692 cases and 27,178 controls followed by a replication analysis using more than 11,000 case-control samples...
February 17, 2018: Carcinogenesis
Batoul Farran, Gregory Dyson, Douglas Craig, Alan Dombkowski, Jennifer L Beebe-Dimmer, Isaac J Powell, Izabela Podgorski, Lance Heilbrun, Susan Bolton, Cathryn H Bock
Prostate cancer is one of the most common cancers in men worldwide. Currently available diagnostic and prognostic tools for this disease, such as PSA, suffer from lack of specificity and sensitivity, resulting in over- and misdiagnosis. Hence, there is an urgent need for clinically relevant biomarkers capable of distinguishing between aggressive and non-aggressive forms of prostate cancer to aid in stratification, management and therapeutic decisions. To address this unmet need, we investigated the patterns of expression of a panel of 68 plasma-derived microRNAs (miRNAs) in a cohort of African American (AA) and European American (EA) prostate cancer patients (n=114)...
February 17, 2018: Carcinogenesis
Asif Khurshid Qazi, Jawed A Siddiqui, Rahat Jahan, Sanjib Chaudhary, Larry A Walker, Zafar Syed, Dwight T Jones, Surinder K Batra, Muzafar A Macha
Cancer remains a leading cause of death in the United States and around the world. Although the current synthetic inhibitors used in targeted therapies have improved patient prognosis, toxicity and development of resistance to these agents remain a challenge. Plant-derived natural products and their derivatives have historically been used to treat various diseases, including cancer. Several leading chemotherapeutic agents are directly or indirectly based on botanical natural products. Beyond these important drugs, however, a number of crude herbal or botanical preparations have also shown promising utility for cancer and other disorders...
February 15, 2018: Carcinogenesis
Bruna Corominas-Faja, Elisabet Cuyàs, Jesús Lozano-Sánchez, Sílvia Cufí, Sara Verdura, Salvador Fernández-Arroyo, Isabel Borrás-Linares, Begoña Martin-Castillo, Ángel G Martin, Ruth Lupu, Alfons Nonell-Canals, Melchor Sanchez-Martinez, Vicente Micol, Jorge Joven, Antonio Segura-Carretero, Javier A Menendez
Targeting tumor-initiating, drug-resistant populations of cancer stem cells (CSC) with phytochemicals is a novel paradigm for cancer prevention and treatment. We herein employed a phenotypic drug discovery approach coupled to mechanism-of-action profiling and target deconvolution to identify phenolic components of extra virgin olive oil (EVOO) capable of suppressing the functional traits of CSC in breast cancer (BC). In vitro screening revealed that the secoiridoid decarboxymethyl oleuropein aglycone (DOA) could selectively target sub-populations of epithelial-like, aldehyde dehydrogenase (ALDH)-positive and mesenchymal-like, CD44+CD24-/low CSC...
February 14, 2018: Carcinogenesis
Zhi-Liang Wang, Chuan-Bao Zhang, Zheng Wang, Xiang-Qi Meng, Xiao-Juan Liu, Bo Han, Chun-Bin Duan, Jin-Quan Cai, Zhong-Fei Hao, Ming-Hui Chen, Tao Jiang, Yong-Li Li, Chuan-Lu Jiang, Hong-Jun Wang
Gliomas are characterized by a malignant phenotype with proliferation, cell cycle arrest and invasion. To explore the biological consequences of epigenetically regulated miRNAs, we performed a microarray based screening (whose expression was affected by 5-AZA treatment) followed by bisulfite sequencing validation. We found that miR-134 as an epigenetically regulated suppressor gene with prognostic value in gliomas. MicroRNA-134 was downregulated in high grade gliomas, especially in GBM samples. Functional studies in vitro and in vivo in mouse models showed that overexpression of miR-134 was sufficient to reduce cell cycle arrest, cell proliferation and invasion...
February 8, 2018: Carcinogenesis
Shiv Ram Krishn, Koelina Ganguly, Sukhwinder Kaur, Surinder K Batra
Heavily glycosylated secreted mucin MUC5AC, by the virtue of its cysteine rich repeats can form inter- and intramolecular disulphide linkages resulting in complex polymers, which in turn craft the framework of the polymeric mucus gel on epithelial cell surfaces. MUC5AC is a molecule with versatile functional implications including barrier functions to epithelial cells, host-pathogen interaction, immune cell attraction to sites of pre-malignant or malignant lesions and tumor progression in a context-dependent manner...
February 5, 2018: Carcinogenesis
Guosong Jiang, Chao Huang, Jingxia Li, Haishan Huang, Jingjing Wang, Yawei Li, Fei Xie, Honglei Jin, Junlan Zhu, Chuanshu Huang
There are few approved drugs available for the treatment of muscle invasive bladder cancer. Recently, we have demonstrated that Isorhapontigenin (ISO), a new derivative isolated from the Chinese herb Gnetum Cleistostachyum, effectively induces cell-cycle arrest at the G0/G1 phase and inhibits anchorage-independent cell growth through the miR-137/Sp1/cyclin D1 axis in human muscle invasive bladder cancer cells. Herein, we found that treatment of bladder cancer (BC) cells with Isorhapontigenin resulted in a significant upregulation of p27, which was also observed in ISO-treated mouse BCs that were induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)...
February 2, 2018: Carcinogenesis
Eugenia Hernández-Ruiz, Agustí Toll, Irene García-Diez, Evelyn Andrades, Carla Ferrandiz-Pulido, Emili Masferrer, Mireia Yébenes, Ane Jaka, Javier Gimeno, Ramón Gimeno, Vicenç García-Patos, Ramón M Pujol, Inmaculada Hernández-Muñoz
Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy in humans and approximately 5% metastasize, usually to regional lymph nodes. Epigenetic regulation of gene expression may allow tumoral cells to acquire new functions in order to escape from the primary tumor. The aim of this study was to investigate the expression and function of proteins of the Polycomb family of epigenetic regulators in the metastatic process of cSCC. A higher expression of RING1B and EZH2 was detected by immunohistochemistry in a series of primary cSCC tumors that metastasized (MSCC) when compared to non-metastasizing cSCC (non-MSCC)...
January 31, 2018: Carcinogenesis
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