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https://www.readbyqxmd.com/read/29334255/ngs-based-methylation-profiling-differentiates-tcf3-hlf-and-tcf3-pbx1-positive-b-cell-acute-lymphoblastic-leukemia
#1
Priyadarshini Kachroo, Silke Szymczak, Femke-Anouska Heinsen, Michael Forster, Jörn Bethune, Georg Hemmrich-Stanisak, Lewis Baker, Martin Schrappe, Martin Stanulla, Andre Franke
AIM: To determine whether methylation differences between mostly fatal TCF3-HLF and curable TCF3-PBX1 pediatric acute lymphoblastic leukemia subtypes can be associated with differential gene expression and remission. MATERIALS & METHODS: Five (extremely rare) TCF3-HLF versus five (very similar) TCF3-PBX1 patients were sampled before and after remission and analyzed using reduced representation bisulfite sequencing and RNA-sequencing. RESULTS: We identified 7000 differentially methylated CpG sites between subtypes, of which 78% had lower methylation levels in TCF3-HLF...
January 15, 2018: Epigenomics
https://www.readbyqxmd.com/read/29262330/hepatic-leukemia-factor-maintains-quiescence-of-hematopoietic-stem-cells-and-protects-the-stem-cell-pool-during-regeneration
#2
Karolina Komorowska, Alexander Doyle, Martin Wahlestedt, Agatheeswaran Subramaniam, Shubhranshu Debnath, Jun Chen, Shamit Soneji, Ben Van Handel, Hanna K A Mikkola, Kenichi Miharada, David Bryder, Jonas Larsson, Mattias Magnusson
The transcription factor hepatic leukemia factor (HLF) is strongly expressed in hematopoietic stem cells (HSCs) and is thought to influence both HSC self-renewal and leukemogenesis. However, the physiological role of HLF in hematopoiesis and HSC function is unclear. Here, we report that mice lacking Hlf are viable with essentially normal hematopoietic parameters, including an intact HSC pool during steady-state hematopoiesis. In contrast, when challenged through transplantation, Hlf-deficient HSCs showed an impaired ability to reconstitute hematopoiesis and became gradually exhausted upon serial transplantation...
December 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/29251327/survival-pathway-of-cholangiocarcinoma-via-akt-mtor-signaling-to-escape-raf-mek-erk-pathway-inhibition-by-sorafenib
#3
Kenta Yokoi, Akira Kobayashi, Hiroaki Motoyama, Masato Kitazawa, Akira Shimizu, Tsuyoshi Notake, Takahide Yokoyama, Tomio Matsumura, Michiko Takeoka, Shin-Ichi Miyagawa
Cholangiocarcinoma (CCC) is a strongly aggressive malignancy for which surgical resection is the only potential curative therapy. Sorafenib, a multikinase inhibitor of the RAF/MEK/ERK pathway, is a molecular-targeted drug that is approved for hepatocellular carcinoma (HCC) but not for CCC. The differences in signaling pathway characteristics under sorafenib treatment between HCC (HLF, Huh7, PLC/PRF/5) and CCC (RBE, YSCCC, Huh28) cell lines were therefore investigated using cell proliferation, western blotting, and apoptosis analyses...
February 2018: Oncology Reports
https://www.readbyqxmd.com/read/29242152/human-umbilical-cord-derived-mesenchymal-stem-cells-protect-from-hyperoxic-lung-injury-by-ameliorating-aberrant-elastin-remodeling-in-the-lung-of-o2-exposed-newborn-rat
#4
Chen Hou, Danyi Peng, Li Gao, Daiyin Tian, Jihong Dai, Zhengxiu Luo, Enmei Liu, Hong Chen, Lin Zou, Zhou Fu
The incidence and mortality rates of bronchopulmonary dysplasia (BPD) remain very high. Therefore, novel therapies are imminently needed to improve the outcome of this disease. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) show promising therapeutic effects on oxygen-induced model of BPD. In our experiment, UC-MSCs were intratracheally delivered into the newborn rats exposed to hyperoxia, a well-established BPD model. This study demonstrated that UC-MSCs reduce elastin expression stimulated by 90% O2 in human lung fibroblasts-a (HLF-a), and inhibit HLF-a transdifferentiation into myofibroblasts...
December 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29234372/hawthorn-leaf-flavonoids-protect-against-diabetes-induced-cardiomyopathy-in-rats-via-pkc-%C3%AE-signaling-pathway
#5
Qing Min, Yuting Bai, Yuchen Zhang, Wei Yu, Minli Zhang, Dongyang Liu, Tingting Diao, Wei Lv
Objectives: DCM has become one of the main reasons of death in diabetic patients. In this study, we aimed to explore the hawthorn leaf flavonoids (HLF) protective effect against diabetes-induced cardiac injury and the underlying mechanisms in experimental rats. Methods: Experimental diabetic model was induced by intraperitoneal injection of streptozotocin (STZ, 40 mg/kg) in rats after feeding with high-fat diet for 8 weeks. The diabetic rats received a 16-week treatment of different doses of HLF (50, 100, and 200)...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29180990/the-n-terminus-of-human-lactoferrin-displays-anti-biofilm-activity-on-candida-parapsilosis-in-lumen-catheters
#6
Roberta Fais, Mariagrazia Di Luca, Cosmeri Rizzato, Paola Morici, Daria Bottai, Arianna Tavanti, Antonella Lupetti
Candida parapsilosis is a major cause of hospital-acquired infection, often related to parenteral nutrition administered via catheters and hand colonization of health care workers, and its peculiar biofilm formation ability on plastic surfaces. The mortality rate of 30% points to the pressing need for new antifungal drugs. The present study aimed at analyzing the inhibitory activity of the N-terminal lactoferrin-derived peptide, further referred to as hLF 1-11, against biofilms produced by clinical isolates of C...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29166614/critical-modulation-of-hematopoietic-lineage-fate-by-hepatic-leukemia-factor
#7
Martin Wahlestedt, Vasileios Ladopoulos, Isabel Hidalgo, Manuel Sanchez Castillo, Rebecca Hannah, Petter Säwén, Haixia Wan, Monika Dudenhöffer-Pfeifer, Mattias Magnusson, Gudmundur L Norddahl, Berthold Göttgens, David Bryder
A gradual restriction in lineage potential of multipotent stem/progenitor cells is a hallmark of adult hematopoiesis, but the underlying molecular events governing these processes remain incompletely understood. Here, we identified robust expression of the leukemia-associated transcription factor hepatic leukemia factor (Hlf) in normal multipotent hematopoietic progenitors, which was rapidly downregulated upon differentiation. Interference with its normal downregulation revealed Hlf as a strong negative regulator of lymphoid development, while remaining compatible with myeloid fates...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29126429/rna-sequencing-analysis-of-lung-primary-fibroblast-response-to-eosinophil-degranulation-products-predicts-downstream-effects-on-inflammation-tissue-remodeling-and-lipid-metabolism
#8
Stephane Esnault, Ksenija Bernau, Elizabeth E Torr, Yury A Bochkov, Nizar N Jarjour, Nathan Sandbo
BACKGROUND: The association of eosinophils with inflammation and tissue remodeling is at least partially due to their release of toxic granule proteins and other mediators, including cytokines. Tissue remodeling and consequent functional defects are affected by activity of connective tissue fibroblasts. Exaggerated fibroblast activation, accumulation and change of phenotype may lead to fibrosis and loss of tissue function. So far, little information has been reported on how eosinophils affect inflammation and tissue remodeling via the activation of fibroblasts...
November 10, 2017: Respiratory Research
https://www.readbyqxmd.com/read/29077781/a-gene-signature-to-predict-high-tumour-infiltrating-lymphocytes-after-neoadjuvant-chemotherapy-and-outcome-in-patients-with-triple-negative-breast-cancer
#9
C Criscitiello, M A Bayar, G Curigliano, F W Symmans, C Desmedt, H Bonnefoi, B Sinn, G Pruneri, C Vicier, J Y Pierga, C Denkert, S Loibl, C Sotiriou, S Michiels, F André
INTRODUCTION: In patients with triple-negative breast cancer (TNBC), the extent of tumor-infiltrating lymphocytes (TILs) in the residual disease (RD) after neoadjuvant chemotherapy (NACT) is associated with better prognosis. Our objective was to develop a gene signature from pre-treatment samples to predict the extent of TILs after NACT, and then to test its prognostic value on survival. PATIENTS AND METHODS: Using 99 pre-treatment samples, we generated a four-gene signature associated with high post-NACT TILs...
October 25, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29075151/sporadic-pcdh18-somatic-mutations-in-epcam-positive-hepatocellular-carcinoma
#10
Takehiro Hayashi, Taro Yamashita, Hikari Okada, Kouki Nio, Yasumasa Hara, Yoshimoto Nomura, Tomoyuki Hayashi, Yoshiro Asahina, Mariko Yoshida, Naoki Oishi, Hajime Sunagozaka, Hajime Takatori, Masao Honda, Shuichi Kaneko
BACKGROUND: The relationship between specific genome alterations and hepatocellular carcinoma (HCC) cancer stem cells (CSCs) remains unclear. In this study, we evaluated the relationship between somatic mutations and epithelial cell adhesion molecule positive (EpCAM(+)) CSCs. METHODS: Two patient-derived HCC samples (HCC1 and HCC2) were sorted by EpCAM expression and analyzed by whole exome sequence. We measured PCDH18 expression level in eight HCC cell lines as well as HCC1 and HCC2 by real-time quantitative RT-PCR...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/29048654/telmisartan-inhibits-hepatocellular-carcinoma-cell-proliferation-in-vitro-by-inducing-cell-cycle-arrest
#11
Kyoko Oura, Tomoko Tadokoro, Shintaro Fujihara, Asahiro Morishita, Taiga Chiyo, Eri Samukawa, Yoshimi Yamana, Koji Fujita, Teppei Sakamoto, Takako Nomura, Hirohito Yoneyama, Hideki Kobara, Hirohito Mori, Hisakazu Iwama, Keiichi Okano, Yasuyuki Suzuki, Tsutomu Masaki
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and the third leading cause of cancer-related death. Telmisartan, a widely used antihypertensive drug, is an angiotensin II type 1 (AT1) receptor blocker (ARB) that might inhibit cancer cell proliferation, but the mechanisms through which telmisartan affects various cancers remain unknown. The aim of the present study was to evaluate the effects of telmisartan on human HCC and to assess the expression of microRNAs (miRNAs). We studied the effects of telmisartan on HCC cells using the HLF, HLE, HepG2, HuH-7 and PLC/PRF/5 cell lines...
September 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29032339/synthesis-and-evaluation-of-anticancer-activity-of-boc26p-an-ortho-aryl-chalcone-sodium-phosphate-as-water-soluble-prodrugs-in-vitro-and-in-vivo
#12
Cuige Zhu, Ruimin Wang, Weichao Zheng, Daoyuan Chen, Xin Yue, Yingnan Cao, Wenjing Qin, Haixia Sun, Youqiao Wang, Ziyi Liu, Baojian Li, Jun Du, Xianzhang Bu, Binhua Zhou
Major limitations of chalcones as clinical anticancer agents are water insolubility and poor bioavailability, which may be improved by a classic phosphate prodrug strategy that targets non-specific alkaline phosphatase (ALP) for releasing the parent drug in vivo. In this study, we found that BOC26P, a phosphate prodrug of chalcone OC26, exhibits excellent water solubility and improved plasma concentration in vivo by either i.v. or p.o. compared with the parent drug. In pace with decreased inhibitory activity of BOC26P against microtubule polymerization in vitro and in cells, the antiproliferative activity of BOC26P is attenuated in A549 and HLF cells...
October 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28960191/meis2-as-a-critical-player-in-mn1-induced-leukemia
#13
C K Lai, G L Norddahl, T Maetzig, P Rosten, T Lohr, L Sanchez Milde, N von Krosigk, T R Docking, M Heuser, A Karsan, R K Humphries
Meningioma 1 (MN1) is an independent prognostic marker for normal karyotype acute myeloid leukemia (AML), with high expression linked to all-trans retinoic acid resistance and poor survival. MN1 is also a potent and sufficient oncogene in murine leukemia models, strongly dependent on the MEIS1/AbdB-like HOX protein complex to transform common myeloid progenitors, block myeloid differentiation, and promote leukemic stem cell self-renewal. To identify key genes and pathways underlying leukemic activity, we functionally assessed MN1 cell phenotypic heterogeneity, revealing leukemic and non-leukemic subsets...
September 29, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28956385/-design-and-fabrication-of-a-microfluidic-chip-for-the-co-culture-of-three-cell-types
#14
Shuaichao Wang, Yuqing Ge, Lei Wu, Hui Guo, Shiping Yang, Qinghui Jin
Here a microfluidic chip with 'micro-dam' and 'micro-gap' has been designed and fabricated. It could isolate different cells and flow of medium in each region. It was found that the chip could realize the cells co-culture and patterning of human lung adenocarcinoma cell (A549), human embryonic lung fibroblast (HLF-1) and human endothelial cells (HUVECs), respectively. After 72 hours of culture, three kinds of cells grew well. It provided a developing technical platform for cell related research.
February 25, 2017: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
https://www.readbyqxmd.com/read/28951217/assessing-molecular-initiating-events-mies-key-events-kes-and-modulating-factors-mfs-for-styrene-responses-in-mouse-lungs-using-whole-genome-gene-expression-profiling-following-1-day-and-multi-week-exposures
#15
Melvin E Andersen, George Cruzan, Michael B Black, Salil N Pendse, Darol Dodd, James S Bus, Satinder S Sarang, Marcy I Banton, Robbie Waites, Patrick D McMullen
Styrene increased lung tumors in mice at chronic inhalation exposures of 20ppm and greater. MIEs, KEs and MFs were examined using gene expression in three strains of male mice (the parental C57BL/6 strain, a CYP2F2(-/-) knock out and a CYP2F2(-/-) transgenic containing human CYP2F1, 2A13 and 2B6). Exposures were for 1-day and 1, 4 and 26weeks. After 1-day exposures at 1, 5, 10, 20, 40 and 120ppm significant increases in differentially expressed genes (DEGs) occurred only in parental strain lungs where there was already an increase in DEGs at 5ppm and then many thousands of DEGs by 120ppm...
November 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28943934/l-securinine-inhibits-the-proliferation-of-a549-lung-cancer-cells-and-promotes-dkk1-promoter-methylation
#16
Shuwen Han, Xi Yang, Yuefen Pan, Quan Qi, Junjun Shen, Huifen Fang, Zhaoning Ji
L-securinine is a natural product extracted and isolated from the leaf of dried Securinega suffruticosa. The aim of the present study was to explore the effects of L-securinine on proliferation, and the methylation profile of the dickkopf-related protein 1 (DKK1) gene in human lung cancer cells and fibroblasts. L-securinine was extracted, isolated and the structure was identified. The cytotoxicity of L-securinine in A549 cells was evaluated by Cell Counting Kit-8 assays. The expression and DNA methylation profile of DKK genes was analyzed by reverse transcription-quantitative polymerase chain reaction and bisulfite sequencing polymerase chain reaction, respectively...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28914813/lactoferrin-a-natural-glycoprotein-involved-in-iron-and-inflammatory-homeostasis
#17
REVIEW
Luigi Rosa, Antimo Cutone, Maria Stefania Lepanto, Rosalba Paesano, Piera Valenti
Human lactoferrin (hLf), an iron-binding multifunctional cationic glycoprotein secreted by exocrine glands and by neutrophils, is a key element of host defenses. HLf and bovine Lf (bLf), possessing high sequence homology and identical functions, inhibit bacterial growth and biofilm dependently from iron binding ability while, independently, bacterial adhesion to and the entry into cells. In infected/inflamed host cells, bLf exerts an anti-inflammatory activity against interleukin-6 (IL-6), thus up-regulating ferroportin (Fpn) and transferrin receptor 1 (TfR1) and down-regulating ferritin (Ftn), pivotal actors of iron and inflammatory homeostasis (IIH)...
September 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28878310/large-scale-production-of-recombinant-human-lactoferrin-from-high-expression-marker-free-transgenic-cloned-cows
#18
Ming Wang, Zhaolin Sun, Tian Yu, Fangrong Ding, Ling Li, Xi Wang, Mingbo Fu, Haiping Wang, Jinming Huang, Ning Li, Yunping Dai
Human lactoferrin (hLF) is a valuable protein for pharmaceutical products and functional foods, and worldwide demand for this protein has steadily increased. However, large-scale recombinant human lactoferrin (rhLF) production using current animal bioreactor techniques is limited by the low expression of foreign proteins, the use of antibiotic resistance genes and the down-regulation of endogenous milk proteins. Here, we generated a herd of marker-free, hLF bacterial artificial chromosome (BAC) transgenic cloned cows, as confirmed by Polymerase chain reaction, Southern blot and Western blot analyses...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28877257/rosmarinic-acid-potentiates-carnosic-acid-induced-apoptosis-in-lung-fibroblasts
#19
Sana Bahri, Frédérique Mies, Ridha Ben Ali, Mona Mlika, Saloua Jameleddine, Kathleen Mc Entee, Vadim Shlyonsky
Pulmonary fibrosis is characterized by over-population and excessive activation of fibroblasts and myofibroblasts disrupting normal lung structure and functioning. Rosemary extract rich in carnosic acid (CA) and rosmarinic acid (RA) was reported to cure bleomycin-(BLM)-induced pulmonary fibrosis. We demonstrate that CA decreased human lung fibroblast (HLF) viability with IC50 value of 17.13±1.06 μM, while RA had no cytotoxic effect. In the presence of 50 μM of RA, dose-response for CA shifted to IC50 value of 11...
2017: PloS One
https://www.readbyqxmd.com/read/28860144/ipf-lung-fibroblasts-have-a-senescent-phenotype
#20
Diana Álvarez, Nayra Cárdenes, Jacobo Sellarés, Marta Bueno, Catherine Corey, Vidya Sagar Hanumanthu, Yating Peng, Hannah D'Cunha, John Sembrat, Mehdi Nouraie, Swaroop Shanker, Chandler Caufield, Sruti Shiva, Mary Armanios, Ana L Mora, Mauricio Rojas
The mechanisms of aging that are involved in the development of idiopathic pulmonary fibrosis (IPF) are still unclear. Although it has been hypothesized that the proliferation and activation of human lung fibroblasts (hLFs) are essential in IPF, no studies have assessed how this process works in an aging lung. Our goal was to elucidate if there were age-related changes on primary hLFs isolated from IPF lungs compared with age-matched controls. We investigated several hallmarks of aging in hLFs from IPF patients and age-matched controls...
December 1, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
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