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https://www.readbyqxmd.com/read/29454754/mutational-analysis-of-akt1-and-pik3ca-in-intraductal-papillomas-of-the-breast-with-special-reference-to-cellular-components
#1
Chieko Mishima, Naofumi Kagara, Jun-Ichiro Ikeda, Eiichi Morii, Tomohiro Miyake, Tomonori Tanei, Yasuto Naoi, Masafumi Shimoda, Kenzo Shimazu, Seung Jin Kim, Shinzaburo Noguchi
The pathological feature of intraductal papillomas is defined as a papillary structure composed of a fibrovascular stromal core lined by luminal epithelial cells and myoepithelial cells. We used droplet digital PCR for the mutational analysis of AKT1 (E17K) and PIK3CA (H1047R, E542K, and E545K) in 60 papillomas. AKT1 and PIK3CA mutations were detected in 12 (20%) and 17 (28%) of the papillomas, respectively. In five tumors harboring mutations, mutational analysis of AKT1 or PIK3CA was performed separately using luminal epithelial cells and myoepithelial cells sorted using anti-CK19 antibody and anti-SMA antibody...
February 15, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29448860/therapeutic-ionizing-radiation-induced-bone-loss-a-review-of-in-vivo-and-in-vitro-findings
#2
Jian Zhang, Xinyu Qiu, Kedi Xi, Wentao Hu, Hailong Pei, Jing Nie, Ziyang Wang, Jiahan Ding, Peng Shang, Bingyan Li, Guangming Zhou
Radiation therapy is one of the routine treatment modalities for cancer patients. Ionizing radiation (IR) can induce bone loss, and consequently increases the risk of fractures with delayed and nonunion of the bone in the cancer patients who receive radiotherapy. The orchestrated bone remodeling can be disrupted due to the affected behaviors of bone cells, including bone mesenchymal stem cells (BMSCs), osteoblasts and osteoclasts. BMSCs and osteoblasts are relatively radioresistant compared with osteoclasts and its progenitors...
February 15, 2018: Connective Tissue Research
https://www.readbyqxmd.com/read/29445895/on-reprogramming-of-tumor-cells-metabolism-detection-of-glycogen-in-the-cell-lines-of-hepatocellular-origin-with-various-degrees-of-dedifferentiation
#3
Natalya P Teryukova, Victoria V Malkova, Elena I Sakhenberg, Vadim A Ivanov, Natalia N Bezborodkina, Sergei A Snopov
The reprogramming of cancer cells includes shifts in glucose and glycogen metabolism. The aim of our work was to check the ability of forming glycogen grains in hepatocellular tumor cell lines of various dedifferentiation levels. We studied the monolayer culture established in vitro after explanting cells from rat ascites Zajdela hepatoma strain C (ZH-C) as a "parental" line and its five daughter clonal sublines: the holoclonal sublines 3H, 5F, 6H and the meroclonal ones 1E, 9C, which possess, respectively, the properties of cancer stem-like cells (CSLCs) and cancer progenitor-like cells (CPLCs)...
February 14, 2018: Cytotechnology
https://www.readbyqxmd.com/read/29445162/mycn-drives-glutaminolysis-in-neuroblastoma-and-confers-sensitivity-to-an-ros-augmenting-agent
#4
Tingting Wang, Lingling Liu, Xuyong Chen, Yuqing Shen, Gaojian Lian, Nilay Shah, Andrew M Davidoff, Jun Yang, Ruoning Wang
Heightened aerobic glycolysis and glutaminolysis are characteristic metabolic phenotypes in cancer cells. Neuroblastoma (NBL), a devastating pediatric cancer, is featured by frequent genomic amplification of MYCN, a member of the Myc oncogene family that is primarily expressed in the early stage of embryonic development and required for neural crest development. Here we report that an enriched glutaminolysis gene signature is associated with MYCN amplification in children with NBL. The partial knockdown of MYCN suppresses glutaminolysis in NBL cells...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29438698/programming-of-schwann-cells-by-lats1-2-taz-yap-signaling-drives-malignant-peripheral-nerve-sheath-tumorigenesis
#5
Lai Man Natalie Wu, Yaqi Deng, Jincheng Wang, Chuntao Zhao, Jiajia Wang, Rohit Rao, Lingli Xu, Wenhao Zhou, Kwangmin Choi, Tilat A Rizvi, Marc Remke, Joshua B Rubin, Randy L Johnson, Thomas J Carroll, Anat O Stemmer-Rachamimov, Jianqiang Wu, Yi Zheng, Mei Xin, Nancy Ratner, Q Richard Lu
Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive Schwann cell (SC)-lineage-derived sarcomas. Molecular events driving SC-to-MPNST transformation are incompletely understood. Here, we show that human MPNSTs exhibit elevated HIPPO-TAZ/YAP expression, and that TAZ/YAP hyperactivity in SCs caused by Lats1/2 loss potently induces high-grade nerve-associated tumors with full penetrance. Lats1/2 deficiency reprograms SCs to a cancerous, progenitor-like phenotype and promotes hyperproliferation...
February 12, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29435196/exon-3-mutations-of-ctnnb1-drive-tumorigenesis-a-review
#6
REVIEW
Chao Gao, Yingmei Wang, Russell Broaddus, Longhao Sun, Fengxia Xue, Wei Zhang
The canonical Wnt/β-catenin signaling pathway, an important modulator of progenitor cell proliferation and differentiation, is highly regulated for the maintenance of critical biological homeostasis. Decades of studies in cancer genetics and genomics have demonstrated that multiple genes encoding key proteins in this signaling pathway serve as targets for recurrent mutational alterations. Among these proteins, β-catenin and adenomatosis polyposis coli (APC) are two key nodes. β-catenin contributes in transporting extracellular signals for nuclear programming...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29435028/cd133-expression-and-%C3%AE-fetoprotein-levels-define-novel-prognostic-subtypes-of-hbv-associated-hepatocellular-carcinoma-a-long-term-follow-up-analysis
#7
Xiao-Meng Dai, Sheng-Li Yang, Xiu-Mei Zheng, George G Chen, Jing Chen, Tao Zhang
Hepatocellular carcinoma (HCC) is a highly heterogeneous type of tumor, which may be caused by the stem/progenitor cell features of particular HCC cells. Recent studies have subclassified HCC into different prognostic subtypes according to just one stemness-associated marker. However, one stemness-associated marker is not sufficient to clearly define cancer stem cells, or to decipher the heterogeneous nature of HCC. For a more precise subtype classification for prognostic application, a combination of multiple stemness-associated markers is required...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29433739/stem-cells-seen-through-the-foxo-lens-an-evolving-paradigm
#8
Raymond Liang, Saghi Ghaffari
Stem cells self-renew and differentiate to generate all tissues and cells in the body. Stem cell health promotes adaptive responses to tissue damage or loss and is essential for tissue regeneration with age. In the past decade, the evolutionarily conserved transcription factors FOXO with known functions in promoting healthy aging have emerged as key regulators of stem cell homeostasis in various tissues, including blood, neural, and muscle stem cells. Aberrant FOXO functions have been implicated in a variety of disorders including neurodegenerative, blood, cancer, and diabetes some of which are fostered by abnormal stem cell function...
2018: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/29432181/three-classes-of-recurrent-dna-break-clusters-in-brain-progenitors-identified-by-3d-proximity-based-break-joining-assay
#9
Pei-Chi Wei, Cheng-Sheng Lee, Zhou Du, Bjoern Schwer, Yuxiang Zhang, Jennifer Kao, Jeffrey Zurita, Frederick W Alt
We recently discovered 27 recurrent DNA double-strand break (DSB) clusters (RDCs) in mouse neural stem/progenitor cells (NSPCs). Most RDCs occurred across long, late-replicating RDC genes and were found only after mild inhibition of DNA replication. RDC genes share intriguing characteristics, including encoding surface proteins that organize brain architecture and neuronal junctions, and are genetically implicated in neuropsychiatric disorders and/or cancers. RDC identification relies on high-throughput genome-wide translocation sequencing (HTGTS), which maps recurrent DSBs based on their translocation to "bait" DSBs in specific chromosomal locations...
February 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29429512/effect-of-human-umbilical-cord-blood-derived-cd34-hematopoietic-stem-cell-on-the-expression-of-wnt4-and-p53-genes-in-a-rat-model-of-hepatocellular-carcinoma
#10
Rania Naiem Sherif, Hussein Abdellatif, Noha Hazem, Neven A Ebrahim, Dalia Saleh, Gamal Shiha, Huda Eltahry, Kamal G Botros, Omar M Gabr
BACKGROUND AND AIM OF THE WORK: Hepatocellular carcinoma (HCC) is the most frequent primary liver malignancy. Chronic liver injuries as chronic hepatitis C and hepatitis B viruses, aflatoxins consumption and nonalcoholic fatty liver disease are well-established causes of HCC. HCC is associated with a series of molecular changes, as alternation in glypican-3, P53 expression and Wnt/β-catenin pathway. Hepatic cancer progenitor cells could contribute to HCC development. This research aimed to study the effectiveness of human CD34+ hematopoietic stem cell on Wnt4 and P53 genes expression, histopathological grading and hepatic progenitor cells percentage in HCC rat model...
February 2018: Tissue & Cell
https://www.readbyqxmd.com/read/29421999/dna-double-strand-break-repair-related-synthetic-lethality
#11
Monika Toma, Tomasz Skorski, Tomasz Sliwinski
Cancer is a heterogeneous disease with a high degree of diversity between and within tumors. Our limited knowledge of their biology results in ineffective treatment. However, personalized approach may represent a milestone in the field of anticancer therapy. It can increase specificity of treatment against tumor initiating cancer stem cells (CSCs) and cancer progenitor cells (CPCs) with minimal effect on normal cells and tissues. Cancerous cells carry multiple genetic and epigenetic aberrations which may disrupt pathways essential for cell survival...
January 31, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29420258/single-cell-wnt-signaling-niches-maintain-stemness-of-alveolar-type-2-cells
#12
Ahmad Nabhan, Douglas G Brownfield, Pehr B Harbury, Mark A Krasnow, Tushar J Desai
Alveoli, the lung's respiratory units, are tiny sacs where oxygen enters the bloodstream. They are lined by flat AT1 cells, which mediate gas exchange, and AT2 cells, which secret surfactant. Rare AT2s also function as alveolar stem cells. We show that AT2 lung stem cells display active Wnt signaling and many of them are near single, Wnt-expressing fibroblasts. Blocking Wnt secretion depletes these stem cells. Daughter cells leaving the Wnt niche transdifferentiate into AT1s: maintaining Wnt signaling prevents transdifferentiation whereas abrogating Wnt signaling promotes it...
February 1, 2018: Science
https://www.readbyqxmd.com/read/29417261/the-ratio-of-adscs-to-hsc-progenitors-in-adipose-tissue-derived-svf-may-provide-the-key-to-predict-the-outcome-of-stem-cell-therapy
#13
Mehmet Okyay Kilinc, Antonio Santidrian, Ivelina Minev, Robert Toth, Dobrin Draganov, Duong Nguyen, Elliot Lander, Mark Berman, Boris Minev, Aladar A Szalay
BACKGROUND: Stromal vascular fraction (SVF) represents an attractive source of adult stem cells and progenitors, holding great promise for numerous cell therapy approaches. In 2017, it was reported that 1524 patients received autologous SVF following the enzymatic digestion of liposuction fat. The treatment was safe and effective and patients showed significant clinical improvement. In a collaborative study, we analyzed SVF obtained from 58 patients having degenerative, inflammatory, autoimmune diseases, and advanced stage cancer...
February 7, 2018: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/29416793/dose-and-time-dependence-of-the-host-mediated-response-to-paclitaxel-therapy-a-mathematical-modeling-approach
#14
Madeleine Benguigui, Dror Alishekevitz, Michael Timaner, Dvir Shechter, Ziv Raviv, Sebastien Benzekry, Yuval Shaked
It has recently been suggested that pro-tumorigenic host-mediated processes induced in response to chemotherapy counteract the anti-tumor activity of therapy, and thereby decrease net therapeutic outcome. Here we use experimental data to formulate a mathematical model describing the host response to different doses of paclitaxel (PTX) chemotherapy as well as the duration of the response. Three previously described host-mediated effects are used as readouts for the host response to therapy. These include the levels of circulating endothelial progenitor cells in peripheral blood and the effect of plasma derived from PTX-treated mice on migratory and invasive properties of tumor cells in vitro...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29411522/mapping-the-clec12a-expression-on-myeloid-progenitors-in-normal-bone-marrow-implications-for-understanding-clec12a-related-cancer-stem-cell-biology
#15
Marie Bill, Peter B van Kooten Niekerk, Petter S Woll, Laura Laine Herborg, Anne Stidsholt Roug, Peter Hokland, Line Nederby
The C-type lectin domain family 12, member A (CLEC12A) receptor has emerged as a leukaemia-associated and cancer stem cell marker in myeloid malignancies. However, a detailed delineation of its expression in normal haematopoiesis is lacking. Here, we have characterized the expression pattern of CLEC12A on the earliest stem- and myeloid progenitor subsets in normal bone marrow. We demonstrate distinct CLEC12A expression in the classically defined myeloid progenitors, where on average 39.1% (95% CI [32.5;45.7]) of the common myeloid progenitors (CMPs) expressed CLEC12A, while for granulocyte-macrophage progenitors and megakaryocyte-erythroid progenitors (MEPs), the average percentages were 81...
February 7, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29409855/pdgf-pdgfr-axis-in-the-neural-systems
#16
REVIEW
Susmita Sil, Palsamy Periyasamy, Annadurai Thangaraj, Ernest T Chivero, Shilpa Buch
Platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) are expressed in several cells types including the brain cells such as neuronal progenitors, neurons, astrocytes, and oligodendrocytes. Emerging evidence shows that PDGF-mediated signaling regulates diverse functions in the central nervous system (CNS) such as neurogenesis, cell survival, synaptogenesis, modulation of ligand-gated ion channels, and development of specific types of neurons. Interestingly, PDGF/PDFGR signaling can elicit paradoxical roles in the CNS, depending on the cell type and the activation stimuli and is implicated in the pathogenesis of various neurodegenerative diseases...
January 31, 2018: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/29409832/the-tumor-suppressor-cholesterol-metabolite-dendrogenin-a-is-a-new-class-of-lxr-modulator-activating-lethal-autophagy-in-cancers
#17
REVIEW
Marc Poirot, Sandrine Silvente-Poirot
Dendrogenin A (DDA) is a mammalian cholesterol metabolite recently identified that displays tumor suppressor properties. The discovery of DDA has revealed the existence in mammals of a new metabolic branch in the cholesterol pathway centered on 5,6α-epoxycholesterol and bridging cholesterol metabolism with histamine metabolism. Metabolic studies showed a drop in DDA levels in cancer cells and tumors compared to normal cells, suggesting a link between DDA metabolism deregulation and oncogenesis. Importantly, complementation of cancer cells with DDA induced 1) cancer cell re-differentiation, 2) blockade of 6-oxo-cholestan-3β,5α-diol (OCDO) production, an endogenous tumor promoter and 3) lethal autophagy in tumors...
January 31, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29408647/whole-exome-mutational-and-transcriptional-landscapes-of-combined-hepatocellular-cholangiocarcinoma-and-intrahepatic-cholangiocarcinoma-reveal-molecular-diversity
#18
Zhen-Hao Liu, Bao-Feng Lian, Qiong-Zhu Dong, Han Sun, Jin-Wang Wei, Yuan-Yuan Sheng, Wei Li, Yixue Li, Lu Xie, Lei Liu, Lun-Xiu Qin
BACKGROUND: Primary liver cancer (PLC) is the third largest contributor to cancer mortality in the world. PLC is a heterogeneous disease that encompasses several biologically distinct subtypes including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (CHC). CHC is a distinct, albeit rare, subtype of PLC and is comprised of cells with histopathological features of both HCC and ICC. Several studies have focused on the mutation and expression landscapes of HCC and ICC...
January 31, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29401749/the-fungal-metabolite-eurochevalierine-a-sequiterpene-alkaloid-displays-anti-cancer-properties-through-selective-sirtuin-1-2-inhibition
#19
Michael Schnekenburger, Véronique Mathieu, Florence Lefranc, Jun Young Jang, Marco Masi, Anake Kijjoa, Antonio Evidente, Hyun-Jung Kim, Robert Kiss, Mario Dicato, Byung Woo Han, Marc Diederich
NAD⁺-dependent histone deacetylases (sirtuins) are implicated in cellular processes such as proliferation, DNA repair, and apoptosis by regulating gene expression and the functions of numerous proteins. Due to their key role in cells, the discovery of small molecule sirtuin modulators has been of significant interest for diverse therapeutic applications. In particular, it has been shown that inhibition of sirtuin 1 and 2 activities is beneficial for cancer treatment. Here, we demonstrate that the fungal metabolite eurochevalierine from the fungus Neosartorya pseudofischeri inhibits sirtuin 1 and 2 activities (IC50 about 10 µM) without affecting sirtuin 3 activity...
February 5, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29400695/claudin-18-mediated-yap-activity-regulates-lung-stem-and-progenitor-cell-homeostasis-and-tumorigenesis
#20
Beiyun Zhou, Per Flodby, Jiao Luo, Dan R Castillo, Yixin Liu, Fa-Xing Yu, Alicia McConnell, Bino Varghese, Guanglei Li, Nyam-Osor Chimge, Mitsuhiro Sunohara, Michael N Koss, Wafaa Elatre, Peter Conti, Janice M Liebler, Chenchen Yang, Crystal N Marconett, Ite A Laird-Offringa, Parviz Minoo, Kunliang Guan, Barry R Stripp, Edward D Crandall, Zea Borok
Claudins, the integral tight junction (TJ) proteins that regulate paracellular permeability and cell polarity, are frequently dysregulated in cancer; however, their role in neoplastic progression is unclear. Here, we demonstrated that knockout of Cldn18, a claudin family member highly expressed in lung alveolar epithelium, leads to lung enlargement, parenchymal expansion, increased abundance and proliferation of known distal lung progenitors, the alveolar epithelial type II (AT2) cells, activation of Yes-associated protein (YAP), increased organ size, and tumorigenesis in mice...
February 5, 2018: Journal of Clinical Investigation
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