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https://www.readbyqxmd.com/read/28938700/liver-cancers-with-stem-progenitor-cell-features-a-rare-chemotherapy-sensitive-malignancy
#1
Bruno Christian Köhler, Nina Waldburger, Kai Schlamp, Dirk Jäger, Karl Heinz Weiss, Henning Schulze-Bergkamen, Peter Schirmacher, Christoph Springfeld
Primary liver tumors are a heterogeneous group of malignancies. Besides classical hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC), combined and intermediate forms of liver cancer exist and can express stem-cell markers like nuclear cell adhesion molecule (NCAM-1/CD56), c-kit (CD117) or epithelial cell adhesion molecule (EpCAM) together with high proliferative activity. Liver tumors with progenitor-cell features are associated with an unfavorable prognosis, but the phenotype has not resulted in therapeutic consequences so far...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938696/the-molecular-mechanisms-of-chemoresistance-in-cancers
#2
REVIEW
Hua-Chuan Zheng
Overcoming intrinsic and acquired drug resistance is a major challenge in treating cancer patients because chemoresistance causes recurrence, cancer dissemination and death. This review summarizes numerous molecular aspects of multi-resistance, including transporter pumps, oncogenes (EGFR, PI3K/Akt, Erk and NF-κB), tumor suppressor gene (p53), mitochondrial alteration, DNA repair, autophagy, epithelial-mesenchymal transition (EMT), cancer stemness, and exosome. The chemoresistance-related proteins are localized to extracellular ligand, membrane receptor, cytosolic signal messenger, and nuclear transcription factors for various events, including proliferation, apoptosis, EMT, autophagy and exosome...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938607/hgfl-mediated-ron-signaling-supports-breast-cancer-stem-cell-phenotypes-via-activation-of-non-canonical-%C3%AE-catenin-signaling
#3
Sasha J Ruiz-Torres, Nancy M Benight, Rebekah A Karns, Elyse E Lower, Jun-Lin Guan, Susan E Waltz
Breast cancer stem cells (BCSCs), which drive tumor progression, recurrence, and metastasis, are considered a major challenge for breast cancer treatments, thus the discovery of novel pathways regulating BCSC maintenance remains essential to develop new strategies to effectively target this population and combat disease mortality. The HGFL-RON signaling is overexpressed in human breast cancers and is associated with increased breast cancer progression, metastasis, and poor prognosis. Here, we report that overexpression of RON/MST1R and HGFL/MST1 in cell lines and primary tumors increases BCSC self-renewal, numbers, and tumorigenic potential after syngeneic transplantation...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938604/inflammation-and-stem-markers-association-to-pim1-pim2-kinase-induced-tumors-in-breast-and-uterus
#4
Manuel-Pedro Jiménez-García, Antonio Lucena-Cacace, María-José Robles-Frías, Irene Ferrer, Maja Narlik-Grassow, Carmen Blanco-Aparicio, Amancio Carnero
The PIM family of Ser/Thr kinase proteins has been implicated in tumorigenesis at different levels. PIM proteins are overexpressed in several tumor types and have been associated with chemoresistance. However, their role in hormone-dependent female tissues has not been explored, especially in the uterus, breast and ovary. We generated conditional transgenic mice with confined expression of human PIM1 or PIM2 genes in these tissues. We characterized the tumoral response to these genetic alterations corroborating their role as oncogenes since they induce hyperproliferation in all tissues and tumors in mammary gland and uterus...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938535/accurate-primary-germ-cell-cancer-diagnosis-using-serum-based-microrna-detection-amptsmir-test
#5
Ton van Agthoven, Leendert H J Looijenga
Multiple studies, including various methods and overall limited numbers of mostly heterogeneous cases, indicate that the level of embryonic stem cell microRNAs (miRs) (e.g. 371a-3p, 372-3p, 373-3p, and 367-3p) are increased in serum at primary diagnosis of almost all testicular germ cell cancer (TGCC). Here we determine the status of three of these miRs in serum samples of 250 TGCC patients, collected at time of primary diagnosis, compared with 60 non-TGCC patients and 104 male healthy donors. The levels of miRs were measured by the robust ampTSmiR test, including magnetic bead-based miR isolation and target specific pre-amplification followed by real-time quantitative PCR (RT-qPCR) detection...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938528/p53-independent-p21-induction-by-melk-inhibition
#6
Tatsuo Matsuda, Taigo Kato, Kazuma Kiyotani, Yunus Emre Tarhan, Vassiliki Saloura, Suyoun Chung, Koji Ueda, Yusuke Nakamura, Jae-Hyun Park
MELK play critical roles in human carcinogenesis through activation of cell proliferation, inhibition of apoptosis and maintenance of stemness. Therefore, MELK is a promising therapeutic target for a wide range of cancers. Although p21 is a well-known p53-downstream gene, we found that treatment with a potent MELK inhibitor, OTS167, could induce p21 protein expression in cancer cell lines harboring loss-of-function TP53 mutations. We also confirmed that MELK knockdown by siRNA induced the p21 expression in p53-deficient cancer cell lines and caused the cell cycle arrest at G1 phase...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938237/fertility-restoration-with-spermatogonial-stem-cells
#7
Francesca de Michele, Maxime Vermeulen, Christine Wyns
PURPOSE OF REVIEW: This review evaluates the state of the art in terms of challenges and strategies used to restore fertility with spermatogonial stem cells retrieved from prepubertal boys affected by cancer. Although these boys do not yet produce spermatozoa, the only option to preserve their fertility is cryopreservation of spermatogonial stem cells in the form of testicular cell suspensions or whole tissue pieces. Different techniques have been described to achieve completion of spermatogenesis from human, spermatogonial stem cells but none is yet ready for clinical application...
September 21, 2017: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/28938159/lunatic-fringe-and-p53-cooperatively-suppress-mesenchymal-stem-like-breast-cancer
#8
Wen-Cheng Chung, Shubing Zhang, Lavanya Challagundla, Yunyun Zhou, Keli Xu
Claudin-low breast cancer (CLBC) is a poor prognosis molecular subtype showing stemness and mesenchymal features. We previously discovered that deletion of a Notch signaling modulator, Lunatic Fringe (Lfng), in the mouse mammary gland induced a subset of tumors resembling CLBC. Here we report that deletion of one copy of p53 on this background not only accelerated mammary tumor development but also led to a complete penetrance of the mesenchymal stem-like phenotype. All mammary tumors examined in the Lfng/p53 compound mutant mice displayed a mesenchymal/spindloid pathology...
September 19, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28937680/salinomycin-kills-cancer-stem-cells-by-sequestering-iron-in-lysosomes
#9
Trang Thi Mai, Ahmed Hamaï, Antje Hienzsch, Tatiana Cañeque, Sebastian Müller, Julien Wicinski, Olivier Cabaud, Christine Leroy, Amandine David, Verónica Acevedo, Akihide Ryo, Christophe Ginestier, Daniel Birnbaum, Emmanuelle Charafe-Jauffret, Patrice Codogno, Maryam Mehrpour, Raphaël Rodriguez
Cancer stem cells (CSCs) represent a subset of cells within tumours that exhibit self-renewal properties and the capacity to seed tumours. CSCs are typically refractory to conventional treatments and have been associated to metastasis and relapse. Salinomycin operates as a selective agent against CSCs through mechanisms that remain elusive. Here, we provide evidence that a synthetic derivative of salinomycin, which we named ironomycin (AM5), exhibits a more potent and selective activity against breast CSCs in vitro and in vivo, by accumulating and sequestering iron in lysosomes...
October 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28936851/-research-of-reversal-effect-of-pesv-to-multi-drug-resistance-of-leukemia-stem-cell
#10
Xiang-Dong Yang, Xing-Li Wang, Wen-Hua Yang, Lei Zhao, Tian-Gai Yan
Using the BALB/c mouse multidrug resistance model of leukemia, the effect of peptide extract from scorpion venom (PESV) to the upstream signal factors of P-gp of MDR leukemia stem cells on the mouse tumor block was observed, and the mechanism of PESV to reverse the MDR of LSC was studied. At the same time, the expression of P-gp, MDR1 mRNA and PI3-K, NF-κB were respectively detected through flow cytometry, RT-PCR, Western blot and Elisa, and the mouse liver, spleen were examined via histopathological methods...
December 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28936481/controlling-epithelial-to-mesenchymal-transition-through-acetylation-of-histone-h2bk5
#11
Robert J Mobley, Amy N Abell
Large-scale epigenetic changes take place when epithelial cells with cell-cell adhesion and apical-basal polarity transition into invasive, individual, mesenchymal cells through a process known as epithelial to mesenchymal transition (EMT). Importantly, cancers with stem cell properties disseminate and form distant metastases by reactivating the developmental EMT program. Recent studies have demonstrated that the epigenetic histone modification, H2BK5 acetylation (H2BK5Ac), is important in the regulation of EMT...
September 2017: Journal of Nature and Science
https://www.readbyqxmd.com/read/28935813/asxl3-is-a-novel-pluripotency-factor-in-human-respiratory-epithelial-cells-and-a-potential-therapeutic-target-in-small-cell-lung-cancer
#12
Vivek Shukla, Mahadev Rao, Hongen Zhang, Jeanette Beers, Darawalee Wangsa, Danny Wangsa, Floryne O Buishand, Yonghong Wang, Zhiya Yu, Holly Stevenson, Emily Reardon, Kaitlin C McLoughlin, Andrew Kaufman, Eden Payabyab, Julie A Hong, Mary Zhang, Sean R Davis, Daniel C Edelman, Guokai Chen, Markku Miettinen, Nicholas Restfo, Thomas Ried, Paul S Meltzer, David S Schrump
In this study, we generated induced pluripotent stem cells (iPSC) from normal human small airway epithelial cells (SAEC) to investigate epigenetic mechanisms of stemness and pluripotency in lung cancers. We documented key hallmarks of reprogramming in lung iPSC (Lu-iPSC) that coincided with modulation of more than 15,000 genes relative to parental SAEC. Of particular novelty, we identified the PRC2-associated protein, ASXL3 which was markedly upregulated in Lu-iPSC and small cell lung cancer (SCLC) lines and clinical specimens...
September 21, 2017: Cancer Research
https://www.readbyqxmd.com/read/28935760/ultrasound-reverses-chemo-resistance-in-breast-cancer-stem-cell-like-cells-by-altering-abcg2%C3%A2-expression
#13
Lijuan Guo, Pengfei Zheng, Huijun Fan, Haiyan Wang, Wenzhong Xu, Wenyan Zhou
Doxorubicin (DOX)-resistance in breast cancer largely results from the breast cancer stem cell-like cells (BCSCs) which could be targeted to improve the efficacy of chemotherapy. Cell permeabilization using microbubbles (MB) and ultrasound (US) have the potential for delivering molecules into the cytoplasm. We aim to evaluate a new methodology of US on BCSCs. First, our findings indicated that ALDHA1(+) spheres which were derived from fresh primary breast cancer samples displayed stem cell-like features and were resistant to DOX...
September 21, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28935568/genetically-engineered-oncolytic-newcastle-disease-virus-mediates-cytolysis-of-prostate-cancer-stem-like-cells
#14
Raghunath Shobana, Raghavendra Sumanth Pudupakam, Adria Allen, Moanaro Biswas, Nammalwar Sriranganathan
Oncolytic virotherapy is a promising novel approach that overcomes the limitations posed by radiation and chemotherapy. In this study, the oncolytic efficacy of a recombinant Newcastle disease virus (rNDV) BC-KLQL-GFP, against prostate cancer stem-like/tumor initiating cells was evaluated. Xenograft derived prostaspheres (XPS) induced tumor more efficiently than monolayer cell derived prostaspheres (MCPS) in nude mice. Primary and secondary XPS show enhanced self-renewal and clonogenic potential compared to MCPS...
September 18, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28934561/epigenetic-mechanisms-regulating-adaptive-responses-to-targeted-kinase-inhibitors-in-cancer
#15
Steven P Angus, Jon S Zawistowski, Gary L Johnson
Although targeted inhibition of oncogenic kinase drivers has achieved remarkable patient responses in many cancers, the development of resistance has remained a significant challenge. Numerous mechanisms have been identified, including the acquisition of gatekeeper mutations, activating pathway mutations, and copy number loss or gain of the driver or alternate nodes. These changes have prompted the development of kinase inhibitors with increased selectivity, use of second-line therapeutics to overcome primary resistance, and combination treatment to forestall resistance...
September 15, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/28934364/the-histone-variant-macroh2a-confers-functional-robustness-to-the-intestinal-stem-cell-compartment
#16
Ryan James Cedeno, Angela Nakauka-Ddamba, Maryam Yousefi, Stephanie Sterling, Nicolae Adrian Leu, Ning Li, John R Pehrson, Christopher Joachim Lengner
A stem cell's epigenome directs cell fate during development, homeostasis, and regeneration. Epigenetic dysregulation can lead to inappropriate cell fate decisions, aberrant cell function, and even cancer. The histone variant macroH2A has been shown to influence gene expression, guide cell fate, and safeguard against genotoxic stress. Interestingly, mice lacking functional macroH2A histones (hereafter referred to as macroH2A DKO) are viable and fertile; yet suffer from increased perinatal death and reduced weight and size compared to wildtype (WT)...
2017: PloS One
https://www.readbyqxmd.com/read/28934267/patient-derived-osteosarcoma-cells-are-resistant-to-methotrexate
#17
Amanda Dos Santos Cavalcanti, Walter Meohas, Gabriele de Oliveira Ribeiro, Ana Cristina de Sá Lopes, Sharareh Gholamin, Mostafa Razavi, Taís Hanae Kasai Brunswick, Amir Avan, João Antonio Matheus Guimarães, Maria Eugenia Leite Duarte, Suzana Assad Kahn
Osteosarcoma is the most common primary bone tumor in children and young adults. The median survival of osteosarcoma patients has not significantly improved since 1990, despite administration of different classes of chemotherapy agents, such as methotrexate, cisplatin and doxorubicin. Cancer stem cells (CSCs) are responsible for the resistance of osteosarcoma to chemotherapy and OCT4, SOX2 and SSEA4 have been used to identify CSCs in osteosarcoma. Here, we used low-passage patient-derived osteosarcoma cells and osteosarcoma cells directly isolated from patients before and after chemotherapy treatments to evaluate the effects of chemotherapy on stem cell markers expression...
2017: PloS One
https://www.readbyqxmd.com/read/28934230/e-cadherin-a-determinant-molecule-associated-with-ovarian-cancer-progression-dissemination-and-aggressiveness
#18
Marina Rosso, Blanca Majem, Laura Devis, Lara Lapyckyj, María José Besso, Marta Llauradó, María Florencia Abascal, María Laura Matos, Lucia Lanau, Josep Castellví, José Luis Sánchez, Asunción Pérez Benavente, Antonio Gil-Moreno, Jaume Reventós, Anna Santamaria Margalef, Marina Rigau, Mónica Hebe Vazquez-Levin
Ovarian cancer (OC) is the fifth cancer death cause in women worldwide. The malignant nature of this disease stems from its unique dissemination pattern. Epithelial-to-mesenchymal transition (EMT) has been reported in OC and downregulation of Epithelial cadherin (E-cadherin) is a hallmark of this process. However, findings on the relationship between E-cadherin levels and OC progression, dissemination and aggressiveness are controversial. In this study, the evaluation of E-cadherin expression in an OC tissue microarray revealed its prognostic value to discriminate between advanced- and early-stage tumors, as well as serous tumors from other histologies...
2017: PloS One
https://www.readbyqxmd.com/read/28933990/influence-of-salinomycin-treatment-on-division-and-movement-of-individual-cancer-cells-cultured-in-normoxia-or-hypoxia-evaluated-with-time-lapse-digital-holographic-microscopy
#19
Sofia Kamlund, Daniel Strand, Birgit Janicke, Kersti Alm, Stina Oredsson
Most studies on new cancer drugs are based on population-derived data, where the absence of response of a small population may pass unnoticed. Thus, individual longitudinal tracking of cells is important for the future development of efficient cancer treatments. We have used digital holographic microscopy to track individual JIMT-1 human breast cancer cells and L929 mouse fibroblast cultivated in normoxia or hypoxia. In addition, JIMT-1 cells were treated with salinomycin, a cancer stem cell targeting compound...
September 21, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28933914/comparison-of-cellular-transforming-activity-of-oct4-nanog-and-sox2-in-immortalized-astrocytes
#20
Sunyoung Seo, Hee-Young Jeon, Hyunggee Kim
Embryonic stem cell factors-OCT4, NANOG, and SOX2-contribute to the maintenance of stem cell properties and malignant progression in various cancers, including glioblastoma. Although functional roles of each of these genes are well documented in stem cell and cancer biology, no study has directly compared their cellular transforming activity under same experimental conditions. In this study, we compared the cellular transforming activity of OCT4, NANOG, and SOX2 using human immortalized astrocytes cultured under serum-free stem cell culture conditions...
September 21, 2017: DNA and Cell Biology
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