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https://www.readbyqxmd.com/read/28719907/tumor-heterogeneity-in-lymphomas-a-different-breed
#1
Christian M Schürch, Birgit Federmann, Leticia Quintanilla-Martinez, Falko Fend
The facts that cancer represents tissues consisting of heterogeneous neoplastic, as well as reactive, cell populations and that cancers of the same histotype may show profound differences in clinical behavior have long been recognized. With the advent of new technologies and the demands of precision medicine, the investigation of tumor heterogeneity has gained much interest. An understanding of intertumoral heterogeneity in patients with the same disease entity is necessary to optimally guide personalized treatment...
July 19, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28716944/potent-competitive-inhibition-of-human-ribonucleotide-reductase-by-a-nonnucleoside-small-molecule
#2
Md Faiz Ahmad, Intekhab Alam, Sarah E Huff, John Pink, Sheryl A Flanagan, Donna Shewach, Tessianna A Misko, Nancy L Oleinick, William E Harte, Rajesh Viswanathan, Michael E Harris, Chris Godfrey Dealwis
Human ribonucleotide reductase (hRR) is crucial for DNA replication and maintenance of a balanced dNTP pool, and is an established cancer target. Nucleoside analogs such as gemcitabine diphosphate and clofarabine nucleotides target the large subunit (hRRM1) of hRR. These drugs have a poor therapeutic index due to toxicity caused by additional effects, including DNA chain termination. The discovery of nonnucleoside, reversible, small-molecule inhibitors with greater specificity against hRRM1 is a key step in the development of more effective treatments for cancer...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28714104/chronic-inflammation-elicited-liver-progenitor-cell-conversion-to-liver-cancer-stem-cell-with-clinical-significance
#3
Xiao-Feng Li, Cheng Chen, Dai-Min Xiang, Le Qu, Wen Sun, Xin-Yuan Lu, Teng-Fei Zhou, Shu-Zhen Chen, Bei-Fang Ning, Zhuo Cheng, Ming-Yang Xia, Wei-Feng Shen, Wen Yang, Wen Wen, Terence Kin Wah Lee, Wen-Ming Cong, Hong-Yang Wang, Jin Ding
The substantial heterogeneity and hierarchical organization in liver cancer supports the theory of liver cancer stem cell (LCSC). However, the relationship between chronic hepatic inflammation and LCSC generation remains obscure. Here we observed a close correlation between aggravated inflammation and liver progenitor cell (LPC) propagation in the cirrhotic liver of rats exposed to diethylnitrosamine. LPCs isolated from the rat cirrhotic liver initiated subcutaneous liver cancers in NOD/SCID mice, suggesting the malignant transformation of LPC toward LCSC...
July 17, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28713379/op9-feeder-cells-are-superior-to-m2-10b4-cells-for-the-generation-of-mature-and-functional-natural-killer-cells-from-umbilical-cord-hematopoietic-progenitors
#4
Lara Herrera, Juan Manuel Salcedo, Silvia Santos, Miguel Ángel Vesga, Francisco Borrego, Cristina Eguizabal
Adoptive natural killer (NK) cell therapy relies on the acquisition of large numbers of mature and functional NK cells. An option for future immunotherapy treatments is to use large amounts of NK cells derived and differentiated from umbilical cord blood (UCB) CD34(+) hematopoietic stem cells (HSCs), mainly because UCB is one of the most accessible HSC sources. In our study, we compared the potential of two stromal cell lines, OP9 and M2-10B4, for in vitro generation of mature and functional CD56(+) NK cells from UCB CD34(+) HSC...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28709146/liver-cancers-with-stem-progenitor-cell-features-a-rare-chemotherapy-sensitive-malignancy
#5
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...
June 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28707729/sox11-promotes-invasive-growth-and-dcis-progression
#6
Erik Oliemuller, Naoko Kogata, Philip Bland, Divya Kriplani, Frances Daley, Syed Haider, Vandna Shah, Elinor J Sawyer, Beatrice A Howard
Here, we show that SOX11, an embryonic mammary marker, normally silent in postnatal breast cells, is expressed in many ER-negative (ER-) preinvasive DCIS lesions. Mature mammary epithelial cells engineered to express SOX11 displayed alterations in progenitor cell populations, including an expanded basal-like population with increased ALDH activity, and increased mammosphere-forming capacity. DCIS.com cells engineered to express SOX11 displayed increased ALDH activity, a feature of cancer stem cells. The CD44+/CD24-/ALDH+ cell population was increased in DCIS...
July 14, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28704777/preinvasive-disease-of-the-airway
#7
REVIEW
Ricky M Thakrar, Adam Pennycuick, Elaine Borg, Sam M Janes
Squamous cell carcinoma of the lung arises from preinvasive progenitors in the central airways. The archetypal model appears to be a stepwise morphological progression until there is invasion of the basement membrane. However, not every lesion appears to follow this course and many individuals can have stable disease, or indeed regress to normal epithelium. From our increased understanding of the molecular pathology it is becoming apparent that the respiratory epithelium accumulates progressive genetic and epigenetic insults in response to carcinogens...
July 10, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28700942/a-pml-slit-axis-controls-physiological-cell-migration-and-cancer-invasion-in-the-cns
#8
Valeria Amodeo, Deli A, Joanne Betts, Stefano Bartesaghi, Ying Zhang, Angela Richard-Londt, Matthew Ellis, Rozita Roshani, Mikaella Vouri, Sara Galavotti, Sarah Oberndorfer, Ana Paula Leite, Alan Mackay, Aikaterini Lampada, Eva Wessel Stratford, Ningning Li, David Dinsdale, David Grimwade, Chris Jones, Pierluigi Nicotera, David Michod, Sebastian Brandner, Paolo Salomoni
Cell migration through the brain parenchyma underpins neurogenesis and glioblastoma (GBM) development. Since GBM cells and neuroblasts use the same migratory routes, mechanisms underlying migration during neurogenesis and brain cancer pathogenesis may be similar. Here, we identify a common pathway controlling cell migration in normal and neoplastic cells in the CNS. The nuclear scaffold protein promyelocytic leukemia (PML), a regulator of forebrain development, promotes neural progenitor/stem cell (NPC) and neuroblast migration in the adult mouse brain...
July 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28698860/genomic-profiling-of-chronic-myelogenous-leukemia-basic-and-clinical-approach
#9
REVIEW
Aliasghar Keramatinia, Alireza Ahadi, Mohammad Esmaeil Akbari, Maryam Mohseny, Alireza Mosavi Jarahi, Narjes Mehrvar, Neda Mansouri, S A Mortazavi Tabatabaei, Abolfazl Movafagh
Chronic myeloid leukemia (CML) is a hematological stem cell cancer driven by BCR-ABL1 fusion protein. We review the previous and recent evidence on the significance of CML in diagnostic and clinic management. The technical monitoring of BCR-ABL1 with quantitative real time-PCR has been used in assessing patient outcome. The cytogenetic mark of CML is Philadelphia chromosome, that is formed by reciprocal chromosomal translocations between human chromosome 9 and 22, t(9:22) (q(34):q(11)). It makes a BCR-ABL1 fusion protein with an anomaly tyrosine kinase activity that promotes the characteristic proliferation of progenitor cells in CML and acute lymphoblastic lymphoma...
June 2017: Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28698397/hinokitiol-up-regulates-mir-494-3p-to-suppress-bmi1-expression-and-inhibits-self-renewal-of-breast-cancer-stem-progenitor-cells
#10
Shih-Ming Chen, Bing-Yen Wang, Che-Hsin Lee, Hsueh-Te Lee, Jung-Jung Li, Guan-Ci Hong, Yu-Chieh Hung, Peng-Ju Chien, Che-Ying Chang, Li-Sung Hsu, Wen-Wei Chang
Hinokitiol (β-thujaplicin) is a tropolone-related compound that has anti-microbe, anti-inflammation, and anti-tumor effects. Cancer stem/progenitor cells (CSCs) are a subpopulation of cancer cells with tumor initiation, chemoresistant, and metastatic properties and have been considered the important therapeutic target in future cancer therapy. Previous studies reported that hinokitiol exhibits an anti-cancer activity against murine tumor cells through the induction of autophagy. The current research revealed that hinokitiol suppressed the self-renewal capabilities of human breast CSCs (BCSCs) and inhibited the expression of BMI1 at protein level without suppressing its mRNA...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28695825/tsc2-disruption-in-mesenchymal-progenitors-results-in-tumors-with-vascular-anomalies-overexpressing-lgals3
#11
Peter J Klover, Rajesh L Thangapazham, Jiro Kato, Ji-An Wang, Stasia A Anderson, Victoria Hoffmann, Wendy K Steagall, Shaowei Li, Elizabeth McCart, Neera Nathan, Joshua D Bernstock, Matthew D Wilkerson, Clifton L Dalgard, Joel Moss, Thomas N Darling
Increased mTORC1 signaling from TSC1/TSC2 inactivation is found in cancer and causes tuberous sclerosis complex (TSC). The role of mesenchymal-derived cells in TSC tumorigenesis was investigated through disruption of Tsc2 in craniofacial and limb bud mesenchymal progenitors. Tsc2cKO(Prrx1-cre) mice had shortened lifespans and extensive hamartomas containing abnormal tortuous, dilated vessels prominent in the forelimbs. Abnormalities were blocked by the mTORC1 inhibitor sirolimus. A Tsc2/mTORC1 expression signature identified in Tsc2-deficient fibroblasts was also increased in bladder cancers with TSC1/TSC2 mutations in the TCGA database...
July 11, 2017: ELife
https://www.readbyqxmd.com/read/28693294/upregulated-expression-of-mmp-9-in-gingival-epithelial-cells-induced-by-prolonged-stimulation-with-arecoline
#12
Osamu Uehara, Kousuke Takimoto, Tetsuro Morikawa, Fumiya Harada, Rie Takai, Bhoj Raj Adhikari, Ryoko Itatsu, Tomohisa Nakamura, Koki Yoshida, Hirofumi Matsuoka, Hiroki Nagayasu, Ichiro Saito, Malsantha Muthumala, Itsuo Chiba, Yoshihiro Abiko
Betel quid chewing is implicated in the high prevalence of oral cancer in Southeast Asian countries. One of the major components of betel quid is arecoline. In the present study, in order to characterize the association between chronic arecoline stimulation and carcinogenesis the expression level of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 mRNA in human gingival epithelial progenitor cells (HGEPs) stimulated with arecoline was assessed. The HGEPs were alternated between 3 days of incubation with arecoline (50 µg/ml), and 3 days without arecoline, for up to 30 days...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28693199/epidermal-growth-factor-receptor-in-glioblastoma
#13
Hongsheng Xu, Hailiang Zong, Chong Ma, Xing Ming, Ming Shang, Kai Li, Xiaoguang He, Hai Du, Lei Cao
Mutations in the epidermal growth factor receptor (EGFR) are commonly occurring in glioblastoma. Enhanced activation of EGFR can occur through a variety of different mechanisms, both ligand-dependent and ligand-independent. Numerous evidence has suggested that EGFR is overexpressed in most of primary glioblastomas and some of the secondary glioblastomas and is characteristic of more aggressive glioblastoma phenotypes. Additionally, recent studies have revealed that wild-type EGFR, and to a greater extent hyper-activating EGFR mutants induced a substantial upregulation of Fyn expression...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28690649/overexpression-of-uridine-cytidine-kinase-2-correlates-with-breast-cancer-progression-and-poor-prognosis
#14
Guosong Shen, Pingya He, Yingying Mao, Peipei Li, Frank Luh, Guohui Ding, Xiyong Liu, Yun Yen
PURPOSE: Uridine-cytidine kinase (UCK) 2 is a rate-limiting enzyme involved in the salvage pathway of pyrimidine-nucleotide biosynthesis. Recent studies have shown that UCK2 is overexpressed in many types of cancer and may play a crucial role in activating antitumor prodrugs in human cancer cells. In the current study, we evaluated the potential prognostic value of UCK2 in breast cancer. METHODS: We searched public databases to explore associations between UCK2 gene expression and clinical parameters in patients with breast cancer...
June 2017: Journal of Breast Cancer
https://www.readbyqxmd.com/read/28687780/nuclear-receptors-connect-progenitor-transcription-factors-to-cell-cycle-control
#15
Marta Neto, Marina Naval-Sánchez, Delphine Potier, Paulo S Pereira, Dirk Geerts, Stein Aerts, Fernando Casares
The specification and growth of organs is controlled simultaneously by networks of transcription factors. While the connection between these transcription factors with fate determinants is increasingly clear, how they establish the link with the cell cycle is far less understood. Here we investigate this link in the developing Drosophila eye, where two transcription factors, the MEIS1 homologue hth and the Zn-finger tsh, synergize to stimulate the proliferation of naïve eye progenitors. Experiments combining transcriptomics, open-chromatin profiling, motif analysis and functional assays indicate that these progenitor transcription factors exert a global regulation of the proliferation program...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28684878/hepatocyte-nuclear-factor-1beta-enhances-the-stemness-of-hepatocellular-carcinoma-cells-through-activation-of-the-notch-pathway
#16
Jing-Ni Zhu, Lu Jiang, Jing-Hua Jiang, Xue Yang, Xiao-Yong Li, Jian-Xin Zeng, Rong-Yu Shi, Yang Shi, Xiao-Rong Pan, Zhi-Peng Han, Li-Xin Wei
Hepatocyte nuclear factor-1beta plays an important role in the development and progression of liver cancer. In recent years, the expression of HNF-1β has been reported to be associated with risk for a variety of cancers. The purpose of this study is to investigate whether the expression of HNF-1β promotes the malignancy of HCC and its mechanism. We retrospectively investigated the expression of HNF-1β in 90 patients with hepatocellular carcinoma and found that the high expression of HNF-1β indicated poor prognosis...
July 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28681151/three-dimensional-spatiotemporal-modeling-of-colon-cancer-organoids-reveals-that-multimodal-control-of-stem-cell-self-renewal-is-a-critical-determinant-of-size-and-shape-in-early-stages-of-tumor-growth
#17
Huaming Yan, Anna Konstorum, John S Lowengrub
We develop a three-dimensional multispecies mathematical model to simulate the growth of colon cancer organoids containing stem, progenitor and terminally differentiated cells, as a model of early (prevascular) tumor growth. Stem cells (SCs) secrete short-range self-renewal promoters (e.g., Wnt) and their long-range inhibitors (e.g., Dkk) and proliferate slowly. Committed progenitor (CP) cells proliferate more rapidly and differentiate to produce post-mitotic terminally differentiated cells that release differentiation promoters, forming negative feedback loops on SC and CP self-renewal...
July 5, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/28679862/mysm1-2a-dub-is-an-epigenetic-regulator-in-human-melanoma-and-contributes-to-tumor-cell-growth
#18
Christina Wilms, Carsten M Kroeger, Adelheid V Hainzl, Ishani Banik, Clara Bruno, Ioanna Krikki, Vida Farsam, Meinhard Wlaschek, Martina V Gatzka
Histone modifying enzymes, such as histone deacetylases (HDACs) and polycomb repressive complex (PRC) components, have been implicated in regulating tumor growth, epithelial-mesenchymal transition, tumor stem cell maintenance, or repression of tumor suppressor genes - and may be promising targets for combination therapies of melanoma and other cancers. According to recent findings, the histone H2A deubiquitinase 2A-DUB/Mysm1 interacts with the p53-axis in hematopoiesis and tissue differentiation in mice, in part by modulating DNA-damage responses in stem cell and progenitor compartments...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28679740/role-of-adp-receptors-on-platelets-in-the-growth-of-ovarian-cancer
#19
Min Soon Cho, Kyunghee Noh, Monika Haemmerle, Dan Li, Hyun Park, Qianghua Hu, Takeshi Hisamatsu, Takashi Mitamura, Sze Ling Celia Mak, Satya Kunapuli, Qing Ma, Anil K Sood, Vahid Afshar-Kharghan
We investigated the effect of platelets on ovarian cancer, and role of ADP receptors (P2Y12 and P2Y1) on platelets in the growth of primary ovarian cancer tumors. We showed that in murine models of ovarian cancer, P2Y12 inhibitor (Ticagrelor) reduced tumor growth by 60% compared to aspirin and 75% compared to placebo. In P2Y12(-/-) mice, the growth of syngeneic ovarian cancer tumors was reduced by >85% compared to WT mice. On the other hand, there was no difference in the tumor growth between P2Y1(-/-) and WT mice...
July 5, 2017: Blood
https://www.readbyqxmd.com/read/28677663/inter-strain-differences-in-line-1-dna-methylation-in-the-mouse-hematopoietic-system-in-response-to-exposure-to-ionizing-radiation
#20
Isabelle R Miousse, Jianhui Chang, Lijian Shao, Rupak Pathak, Étienne Nzabarushimana, Kristy R Kutanzi, Reid D Landes, Alan J Tackett, Martin Hauer-Jensen, Daohong Zhou, Igor Koturbash
Long Interspersed Nuclear Element 1 (LINE-1) retrotransposons are the major repetitive elements in mammalian genomes. LINE-1s are well-accepted as driving forces of evolution and critical regulators of the expression of genetic information. Alterations in LINE-1 DNA methylation may lead to its aberrant activity and are reported in virtually all human cancers and in experimental carcinogenesis. In this study, we investigated the endogenous DNA methylation status of the 5' untranslated region (UTR) of LINE-1 elements in the bone marrow hematopoietic stem cells (HSCs), hematopoietic progenitor cells (HPCs), and mononuclear cells (MNCs) in radioresistant C57BL/6J and radiosensitive CBA/J mice and in response to ionizing radiation (IR)...
July 4, 2017: International Journal of Molecular Sciences
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