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the trophoblast model of cancer

Yuxia Sui, Shaoguang Li, Peiying Shi, Youjia Wu, Yuxiang Li, Weiying Chen, Liying Huang, Hong Yao, XinHua Lin
ETHNOPHARMACOLOGICAL RELEVANCE: Selaginella doederleinii Hieron has been used as a folk medicine for the treatment of different cancers, especially for nasopharyngeal carcinoma, lung cancer and trophoblastic tumor in China. Previously, the ethyl acetate extract from S. doederleinii (SDEA extract) showed favorable anti-cancer potentials. However, the main chemical composition and anticancer mechanism of the SDEA extract were still not very clear. Until now, there are no reports available about the oral toxicity of the extract...
August 22, 2016: Journal of Ethnopharmacology
Yuan Mao, Xiaoying Wang, Feng Zheng, Changjun Wang, Qi Tang, Xiaojun Tang, Ning Xu, Huiling Zhang, Dawei Zhang, Lin Xiong, Jie Liang, Jin Zhu
Human trophoblastic cell surface antigen 2 (Trop2) has been reported to act oncogenically. In this study, one-step quantitative real-time polymerase chain reaction (qPCR) test and immunohistochemistry (IHC) analysis with were employed to evaluate the relationship between Trop2 expression and the clinicopathological features of patients with PC. Then a novel anti-Trop2 Fab antibody was conjugated with Doxorubicin (DOX) to form Trop2Fab-DOX, an antibody-drug conjugate. This Trop2Fab-DOX conjugate was characterized by cell ELISA and immunofluorescence assay...
April 26, 2016: Oncotarget
Min Su, Chao Fan, Sainan Gao, Aiguo Shen, Xiaoying Wang, Yuquan Zhang
We investigated the expression of human chorionic gonadotropin (HCG) and its effects on vasculogenic mimicry (VM) formation in ovarian cancer cells under normoxic and hypoxic conditions in three-dimensional matrices preconditioned by an endothelial-trophoblast cell co-culture system. The co-culture model was established using human umbilical vein endothelial cells (HUVECs) and HTR-8 trophoblast cells in a three-dimensional culture system. The co-cultured cells were removed with NH4OH, and ovarian cancer cells were implanted into the preconditioned matrix...
November 2015: Oncology Reports
K Ikeda, C Ueda, K Yamada, A Nakamura, Y Hatsuda, S Kawanishi, S Nishii, M Ogawa
Human choriocarcinoma has been used as a model to study trophoblast transcellular drug transport in the placenta. Previous models had limitations regarding low molecular weight drug transport through the intracellular gap junction. The purpose of this study was to evaluate placental carrier-mediated transport across a differentiating JEG-3 choriocarcinoma cell (DJEGs) layer model in which the intracellular gap junction was restricted. Cimetidine is the substrate of an efflux transporter, breast cancer resistance protein (BCRP)...
July 2015: Die Pharmazie
Yin-Lau Lee, Sze-Wan Fong, Andy C H Chen, Tiantian Li, Chaomin Yue, Cheuk-Lun Lee, Ernest H Y Ng, William S B Yeung, Kai-Fai Lee
STUDY QUESTION: Can human embryonic stem cell-derived trophoblastic spheroids be used to study the early stages of implantation? SUMMARY ANSWER: We generated a novel human embryonic stem cell-derived trophoblastic spheroid model mimicking human blastocysts in the early stages of implantation. WHAT IS KNOWN ALREADY: Both human embryos and choriocarcinoma cell line derived spheroids can attach onto endometrial cells and are used as models to study the early stages of implantation...
November 2015: Human Reproduction
Deepali V Sawant, Kristia Hamilton, Dario A A Vignali
Counter-regulation afforded by specialized regulatory cell populations and immunosuppressive cytokines is critical for balancing immune outcome. The inhibitory potential of the established suppressive cytokines, IL-10 and TGFβ, has been well elucidated in diverse inflammatory scenarios in conjunction with their key roles in Treg development and function. Despite the early predictions for an immunomodulatory role for the Ebi3/p35 heterodimer in placental trophoblasts, IL-35 biology remained elusive until 2007 when it was established as a Treg-restricted inhibitory cytokine...
July 2015: Journal of Interferon & Cytokine Research
Kenneth F Swan, MaryBeth Ferris, Gabriella Pridjian, Deborah E Sullivan, Cindy A Morris
OBJECTIVES: Human cytomegalovirus (HCMV) infection of the placenta is associated with significant pathological consequences, including pregnancy loss, intrauterine growth restriction, preeclampsia and preterm labor. It is thought that some of these pathological anomalies are attributed to the inability of extravillous cytotrophoblasts (EVT) to adequately invade the maternal uterine wall during first trimester pregnancy resulting in impaired remodeling of maternal spiral arteries. Our earlier studies show that HCMV inhibits cytotrophoblast invasion, although the mechanism(s) involved are not fully understood...
January 2015: Pregnancy Hypertension
Annie R A McDougall, Mary Tolcos, Stuart B Hooper, Timothy J Cole, Megan J Wallace
BACKGROUND: Trop2 was first discovered as a biomarker of invasive trophoblast cells. Since then most research has focused on its role in tumourigenesis because it is highly expressed in the vast majority of human tumours and animal models of cancer. It is also highly expressed in stem cells and in many organs during development. RESULTS: We review the multifaceted role of Trop2 during development and tumourigenesis, including its role in regulating cell proliferation and migration, self-renewal, and maintenance of basement membrane integrity...
February 2015: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Jiang Gu, Yu Lei, Yuanping Huang, Yingying Zhao, Jing Li, Tao Huang, Junjun Zhang, Juping Wang, Xiaodong Deng, Zhengshan Chen, Christine Korteweg, Ruishu Deng, Meiling Yan, Qian Xu, Shengnan Dong, Monghong Cai, Lili Luo, Guowei Huang, Yun Wang, Qian Li, Changmei Lin, Meng Su, Chunzhang Yang, Zhengping Zhuang
STUDY QUESTION: How does the placenta protect the fetus from immune rejection by the mother? SUMMARY ANSWER: The placenta can produce IgG that is glycosylated at one of its Fab arms (asymmetric IgG; aIgG) which can interact with other antibodies and certain leukocytes to affect local immune reactions at the junction between the two genetically distinct entities. WHAT IS KNOWN ALREADY: The placenta can protect the semi-allogenic fetus from immune rejection by the immune potent mother...
February 2015: Human Reproduction
George Hu, Mauricio Leal, Qingcong Lin, Timothy Affolter, Puja Sapra, Brian Bates, Marc Damelin
The use of predictive preclinical models in drug discovery is critical for compound selection, optimization, preclinical to clinical translation, and strategic decision-making. Trophoblast glycoprotein (TPBG), also known as 5T4, is the therapeutic target of several anticancer agents currently in clinical development, largely due to its high expression in tumors and low expression in normal adult tissues. In this study, mice were engineered to express human TPBG under endogenous regulatory sequences by replacement of the murine Tpbg coding sequence...
June 1, 2015: Molecular Pharmaceutics
Colin A Ross
John Beard, the British embryologist and histologist, first proposed his trophoblast model of cancer in 1902. The model has subsequently been expanded by Kelley, and in current times, Gonzalez and Isaacs. The trophoblast model of cancer can be stated as a specified, scientifically testable model, including its core predictions that 1) adult stem cells are ectopic trophoblasts that have migrated to other tissues early in embryogenesis; 2) pancreatic enzymes are the key signal that converts the trophoblast into the stable placenta; 3) cancer arises from trophoblasts that have escaped regulatory control; and 4) pancreatic enzymes can be used to treat cancer...
2015: Nutrition and Cancer
Harmeet Singh, Tracy L Nero, Yao Wang, Michael W Parker, Guiying Nie
Mammalian HtrA (high temperature requirement factor A) proteases, comprising 4 multi-domain members HtrA1-4, play important roles in a number of normal cellular processes as well as pathological conditions such as cancer, arthritis, neurodegenerative diseases and pregnancy disorders. However, how HtrA activities are regulated is not well understood, and to date no inhibitors specific to individual HtrA proteins have been identified. Here we investigated five HtrA3 monoclonal antibodies (mAbs) that we have previously produced, and demonstrated that two of them regulated HtrA3 activity in an opposing fashion: one inhibited while the other stimulated...
2014: PloS One
Dariush Mohammadyani, Vladimir A Tyurin, Matthew O'Brien, Yoel Sadovsky, Dmitry I Gabrilovich, Judith Klein-Seetharaman, Valerian E Kagan
Lipid droplets (LDs) are ubiquitous and physiologically active organelles regulating storage and mobilization of lipids in response to metabolic demands. Among the constituent LD neutral lipids, such as triacylglycerols, cholesterol esters, and free fatty acids, oxidizable polyunsaturated molecular species may be quite abundant, yet the structural and functional roles of their oxidation products have not been studied. Our previous work documented the presence of these peroxidized species in LDs. Assuming that hydrophilic oxygen-containing functionalities may markedly change the hydrophobic/hydrophilic molecular balance, here we utilized computational modeling to test the hypothesis that lipid peroxidation causes redistribution of lipids between the highly hydrophobic core and the polar surface (phospho)lipid monolayer-the area enriched with integrated enzymatic machinery...
November 2014: Free Radical Biology & Medicine
Sisi Li, Yongqing Wang, Bin Cao, Yujian Wu, Lei Ji, Yu-xia Li, Ming Liu, Yangyu Zhao, Jie Qiao, Haibing Wang, Hongmei Wang, Chunsheng Han, Yan-ling Wang
CONTEXT: Matrix Metalloproteinase-26 (MMP-26) is the smallest member of matrix metalloproteinase (MMP) family that functions mainly in the extracellular milieu to cleave the extracellular matrix proteins. It is expressed in various cell types of placenta, but its function in placentation has been poorly understood. Considering the existence of a unique cysteine switch sequence in MMP-26 protein sequence, as well as the evidence in cancer cells indicating the digestion of the NH2-terminal domain of ERβ by MMP-26, we hypothesize that MMP-26 may have specific intracellular activity in human placental trophoblast cells...
November 2014: Journal of Clinical Endocrinology and Metabolism
Jane Ireson, Kamaljit Singh, Sarah Gillett, Annie Hills, Jan Everard, Matthew Winter, Robert E Coleman, John Tidy, Barry W Hancock
OBJECTIVE: To describe the evolution of a highly regarded and unique model of multidisciplinary care providing support, monitoring, and treatment for all gestational trophoblastic disease (GTD) patients referred to Sheffield Trophoblastic Disease Centre, 1 of the 3 United Kingdom (UK) supraregional GTD centers. BACKGROUND: The UK GTD service was first established in 1973 and since its inception has centralized care for GTD patients and played a leading international role in developing therapies, management protocols, and biomarker assays with good outcomes for patients...
May 2014: Journal of Reproductive Medicine
Katarzyna Biadasiewicz, Valerie Fock, Sabine Dekan, Katharina Proestling, Philipp Velicky, Sandra Haider, Martin Knöfler, Camilla Fröhlich, Jürgen Pollheimer
ADAM12, consisting of a membrane-bound (ADAM12L) and a secreted (ADAM12S) form, is expressed exclusively in regenerating and developing tissue as well as in certain cancer types. Strong ADAM12 expression levels have been noticed in the human placenta, and deregulated ADAM12S levels were associated with various pregnancy-related disorders including pre-eclampsia and intrauterine growth restriction. However, the role of ADAM12 in trophoblast motility has not been investigated so far. Hence, the present study aimed to investigate the specific function of the protease by using different primary trophoblast cell models...
May 2014: Biology of Reproduction
W Li, D Liu, W Chang, X Lu, Y-L Wang, H Wang, C Zhu, H-Y Lin, Y Zhang, J Zhou, H Wang
The insulin-like growth factor-2 mRNA-binding protein 3 (IGF2BP3) is a member of a highly conserved protein family that is expressed specifically in placenta, testis and various cancers, but is hardly detectable in normal adult tissues. IGF2BP3 has important roles in RNA stabilization and translation, especially during early stages of both human and mouse embryogenesis. Placenta is an indispensable organ in mammalian reproduction that connects developing fetus to the uterine wall, and is responsible for nutrient uptake, waste elimination and gas exchange...
2014: Cell Death & Disease
Zuzana Neumanova, Lukas Cerveny, Martina Ceckova, Frantisek Staud
OBJECTIVE AND DESIGN: Tenofovir (TFV) is used in pregnant women as a part of combination antiretroviral treatment to prevent mother-to-child transmission of HIV infection. We aimed to detect whether TFV and/or its prodrug, tenofovir disoproxil fumarate (TDF), are substrates of ATP-binding cassette (ABC) transporters that are functionally expressed in the placenta, namely P-glycoprotein (ABCB1/MDR1), Breast Cancer Resistance Protein (ABCG2/BCRP) and Multidrug Resistance-Associated Protein 2 (ABCC2/MRP2)...
January 2, 2014: AIDS
M Aghababaei, S Perdu, K Irvine, A G Beristain
During pregnancy, stromal- and vascular-remodeling trophoblasts serve critical roles in directing placental development acquiring pro-invasive characteristics. The A Disintegrin and Metalloproteinase (ADAM) family of multifunctional proteins direct cellular processes across multiple organ systems via their intrinsic catalytic, cell adhesive and intracellular signaling properties. ADAM12, existing as two distinct splice variants (ADAM12L and ADAM12S), is highly expressed in the human placenta and promotes cell migration and invasion in several tumor cell lines; however, its role in trophoblast biology is unknown...
March 2014: Molecular Human Reproduction
Jenni K Repo, Maija Pesonen, Chiara Mannelli, Kirsi Vähäkangas, Jarkko Loikkanen
Human placental trophoblastic cancer BeWo cells can be used as a model of placental trophoblasts. We found that combined exposure to relevant exposure concentrations of ethanol (2‰) and nicotine (15 μM) induces an increase in the amount of reactive oxygen species (ROS). Neither ethanol or nicotine alone, nor their combination affected cell viability. However, nicotine decreased cell proliferation, both alone and combined with ethanol. Nicotine increased the expression of the endoplasmic reticulum (ER)-stress related protein GRP78/BiP, but not another marker of ER-stress, IRE1α...
January 13, 2014: Toxicology Letters
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