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https://www.readbyqxmd.com/read/29782854/combined-treatment-with-sorafenib-and-silibinin-synergistically-targets-both-hcc-cells-and-cancer-stem-cells-by-enhanced-inhibition-of-the-phosphorylation-of-stat3-erk-akt
#1
Jie Mao, Hongbao Yang, Tingting Cui, Pan Pan, Nadia Kabir, Duo Chen, Jinyan Ma, Xingyi Chen, Yijun Chen, Yong Yang
Silibinin, a nontoxic bioactive component in milk thistle, is used as a liver-protective drug in the clinic mainly because of its antioxidant and anti-inflammation activities. In this study, we studied the cytotoxic effects of silibinin combined with sorafenib on hepatocellular carcinoma (HCC). The results indicated that silibinin combined with sorafenib potently inhibited the proliferation of various HCC cells and induced significant apoptosis. In an HCC subcutaneous transplantation tumor model, the combination of silibinin and sorafenib significantly suppressed tumor growth compared with monotherapy...
May 18, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29781803/tendency-of-k562-chronic-myeloid-leukemia-cells-towards-cell-reprogramming
#2
Açelya Yılmazer Aktuna
Cancer cell reprogramming is a potential tool to study cancer progression, disease pathology and drug sensitivity. Prior to performing cancer reprogramming studies, it is important to evaluate the stemness predisposition of cells that will be reprogrammed. Here, we performed a proof-of-concept study with chronic myeloid leukemia K562 cells in order to evaluate their tendency for cancer cell reprogramming. Expression of reprogramming factors, pluripotency markers and tumor-suppressor genes were analyzed at gene and protein level via real-time RT-PCR and flow cytometry...
May 21, 2018: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/29780814/targeting-chronic-myeloid-leukemia-stem-cells-can-transcriptional-program-be-a-druggable-target-for-cancers
#3
REVIEW
Yosuke Masamoto, Mineo Kurokawa
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm resulting from acquisition of constitutively active BCR-ABL protein tyrosine kinase in a hematopoietic stem cell (HSC). Though tyrosine kinase inhibitors (TKIs) have changed a fatal disease into manageable disease, most patients cannot discontinue TKI treatment due to persistence of TKI-resistant leukemia stem cells (LSCs). Much effort has been made to find out factors or pathways specifically operating in LSCs to selectively target LSCs, with some promising results at least in preclinical models...
2018: Stem Cell Investigation
https://www.readbyqxmd.com/read/29773592/investigating-chemoresistance-to-improve-sensitivity-of-childhood-t-cell-acute-lymphoblastic-leukemia-to-parthenolide
#4
Benjamin C Ede, Rafal R Asmaro, John P Moppett, Paraskevi Diamanti, Allison Blair
Current therapies for childhood T cell acute lymphoblastic leukemia have increased survival rates to above 85% in developed countries. Unfortunately, some patients fail to respond to therapy and many suffer from serious side effects, highlighting the need to investigate other agents to treat this disease. Parthenolide, a nuclear factor kappa B inhibitor and reactive oxygen species inducer, has been shown to have excellent anti-cancer activity in pediatric leukemia xenografts, with minimal effects on normal hemopoietic cells...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29772764/the-making-of-leukemia
#5
REVIEW
Inés González-Herrero, Guillermo Rodríguez-Hernández, Andrea Luengas-Martínez, Marta Isidro-Hernández, Rafael Jiménez, Maria Begoña García-Cenador, Francisco Javier García-Criado, Isidro Sánchez-García, Carolina Vicente-Dueñas
Due to the clonal nature of human leukemia evolution, all leukemic cells carry the same leukemia-initiating genetic lesions, independently of the intrinsic tumoral cellular heterogeneity. However, the latest findings have shown that the mode of action of oncogenes is not homogeneous throughout the developmental history of leukemia. Studies on different types of hematopoietic tumors have shown that the contribution of oncogenes to leukemia is mainly mediated through the epigenetic reprogramming of the leukemia-initiating target cell...
May 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29769208/infusion-of-alloanergized-donor-lymphocytes-after-cd34-selected-haploidentical-myeloablative-hematopoietic-stem-cell-transplantation
#6
Jeff K Davies, Lisa L Brennan, John Wingard, Christopher R Cogle, Neena Kapoor, Ami J Shah, Bimalangshu R Dey, Thomas R Spitzer, Marcos De Lima, Laurence Jn Cooper, Peter Thall, Richard E Champlin, Lee M Nadler, Eva C Guinan
PURPOSE: Allogeneic haematopoietic stem-cell transplantation (HSCT) is a curative treatment for many haematologic cancers. Use of haploidentical (mismatched) donors increases HSCT availability but is limited by severe graft-versus-host disease (GvHD) and delayed immune reconstitution. Alloanergization of donor T-cells is a simple approach to rebuild immunity whilst limiting GvHD after haploidentical HSCT but the optimal T-cell dose and impact on immune reconstitution remain unknown.  Experimental Design: We performed a multicentre Phase 1 trial of alloanergized donor lymphocyte infusion (aDLI) after CD34-selected myeloablative haploidentical HSCT...
May 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29741610/aff4-promotes-tumorigenesis-and-tumor-initiation-capacity-of-head-and-neck-squamous-cell-carcinoma-cells-by-regulating-sox2
#7
Peng Deng, Jiongke Wang, Xuefeng Zhang, Xingyu Wu, Ning Ji, Jing Li, Min Zhou, Lu Jiang, Xin Zeng, Qianming Chen
Super elongation complex (SEC) controls gene transcription by releasing Pol II from pausing. Previous studies have shown that dysfunction of SEC was associated with multiple human cancers, such as leukemia and breast cancer. However, the role of SEC in head and neck squamous cell carcinoma (HNSCC) development remains largely unknown. In this study, we found expression of AF4/FMR2 family member 4 (AFF4), the core component of SEC, was upregulated dramatically in HNSCC cell lines and tumor tissues. By using siRNA-mediated depletion and overexpression of AFF4, we demonstrated AFF4 promoted proliferation, migration and invasion of HNSCC cells...
May 8, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29735542/pml-recruits-tet2-to-regulate-dna-modification-and-cell-proliferation-in-response-to-chemotherapeutic-agent
#8
Chengli Song, Lina Wang, Xiaoyan Wu, Kai Wang, Dan Xie, Qi Xiao, Songyu Li, Kui Jiang, Lujian Liao, John R Yates, Jiing-Dwan Lee, Qingkai Yang
Aberrant DNA methylation plays a critical role in the development and progression of cancer. Failure to demethylate and to consequently reactivate methylation-silenced genes in cancer contributes to chemotherapeutic resistance, yet the regulatory mechanisms of DNA demethylation in response to chemotherapeutic agents remain unclear. Here, we show that promyelocytic leukemia (PML) recruits ten-eleven translocation dioxygenase 2 (TET2) to regulate DNA modification and cell proliferation in response to chemotherapeutic agents...
May 7, 2018: Cancer Research
https://www.readbyqxmd.com/read/29734249/endoglin-is-highly-expressed-in-human-mast-cells
#9
Suéllen Trentin Brum, Ana Paula Demasi, Rafael Fantelli Stelini, Maria Letícia Cintra, Vera Cavalcanti de Araujo, Andresa Borges Soares
Endoglin, known to be expressed in proliferating vessels, is of worth when evaluating microvessel density as a prognostic factor in many types of malignancies, including some subtypes of leukemia cells. In childhood acute lymphoblastic leukemia, endoglin is associated with adverse outcome. In bone marrow, endoglin identifies the repopulating hematopoietic stem cells. Mast cells are a component of normal tissue and play an important role in the regulation of several processes, including inflammation and neoplasia...
May 4, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29721072/glucocorticoids-inhibit-oncogenic-runx1-eto-in-acute-myeloid-leukemia-with-chromosome-translocation-t-8-21
#10
Lianghao Lu, Yefei Wen, Yuan Yao, Fengju Chen, Guohui Wang, Fangrui Wu, Jingyu Wu, Padmini Narayanan, Michele Redell, Qianxing Mo, Yongcheng Song
Acute myeloid leukemia (AML) is a major blood cancer with poor prognosis. New therapies are needed to target oncogene-driven leukemia stem cells, which account for relapse and resistance. Chromosome translocation t(8;21), which produces RUNX1-ETO (R-E) fusion oncoprotein, is found in ~13% AML. R-E dominance negatively inhibits global gene expression regulated by RUNX1, a master transcription factor for hematopoiesis, causing increased self-renewal and blocked cell differentiation of hematopoietic progenitor cells, and eventually leukemia initiation...
2018: Theranostics
https://www.readbyqxmd.com/read/29720821/chemical-composition-and-cytotoxic-activity-of-methanol-extract-and-its-fractions-of-streblus-asper-leaves-on-human-cancer-cell-lines
#11
Preeti Rawat, Anil Kumar, Tryambak Deo Singh, Mahesh Pal
Background: Streblus asper , family Moraceae is well-known important medicinal plant used in the Indian system of medicine. In Ayurveda, stem bark of S. asper is recommended against elephantiasis for which there is still no any other effective medicine in the modern system of medicine. Objectives: In the present work, methanol extract (SAM) and its fractions of S. asper leave tested for in vitro anticancer activity against cancer cell lines (MCF-7, A-549, Hep-G2, and K-562) which claims its folklore importance in cancer and gas chromatography-mass spectrometry identification of extracts was also performed...
April 2018: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29720577/universal-monitoring-of-minimal-residual-disease-in-acute-myeloid-leukemia
#12
Elaine Coustan-Smith, Guangchun Song, Sheila Shurtleff, Allen Eng-Juh Yeoh, Wee Joo Chng, Siew Peng Chen, Jeffrey E Rubnitz, Ching-Hon Pui, James R Downing, Dario Campana
BACKGROUND: Optimal management of acute myeloid leukemia (AML) requires monitoring of treatment response, but minimal residual disease (MRD) may escape detection. We sought to identify distinctive features of AML cells for universal MRD monitoring. METHODS: We compared genome-wide gene expression of AML cells from 157 patients with that of normal myeloblasts. Markers encoded by aberrantly expressed genes, including some previously associated with leukemia stem cells, were studied by flow cytometry in 240 patients with AML and in nonleukemic myeloblasts from 63 bone marrow samples...
May 3, 2018: JCI Insight
https://www.readbyqxmd.com/read/29703819/new-insights-from-studies-of-clonal-hematopoiesis
#13
Christopher J Gibson, David P Steensma
Clonal hematopoiesis (CH) describes an asymptomatic expansion of blood cells descended from a single hematopoietic stem cell. Recent studies have shown that CH increases in frequency with aging, and is often driven by somatic mutations in genes that are recurrently mutated in hematologic malignancies. When CH is associated with a mutation in a leukemia-associated gene at a variant allele frequency of 0.02 or greater, it is termed "clonal hematopoiesis of indeterminate potential" (CHIP).  CHIP has a 0...
April 27, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29698587/selective-induction-of-cancer-cell-death-by-vdac1-based-peptides-and-their-potential-use-in-cancer-therapy
#14
Anna Shteinfer-Kuzmine, Zohar Amsalem, Tasleem Arif, Alexandra Zooravlov, Varda Shoshan-Barmatz
Mitochondrial VDAC1 mediates cross-talk between the mitochondria and other parts of the cell by transporting anions, cations, ATP, Ca2+ and metabolites, and serves as a key player in apoptosis. As such, VDAC1 is involved in two important hallmarks of cancer development, namely energy and metabolic reprograming and apoptotic cell death evasion. We previously developed cell-penetrating VDAC1-derived peptides that interact with hexokinase (HK), Bcl-2 and Bcl-xL to prevent the anti-apoptotic activities of these proteins and induce cancer cell death, with a focus on leukemia and glioblastoma...
April 26, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29698131/exposure-of-the-bone-marrow-microenvironment-to-simulated-solar-and-galactic-cosmic-radiation-induces-biological-bystander-effects-on-human-hematopoiesis
#15
Graça Almeida-Porada, Christopher Rodman, Bradford Kuhlman, Egil Brudvik, John Moon, Sunil George, Peter Guida, Satria P Sajuthi, Carl D Langefeld, Stephen J Walker, Paul F Wilson, Christopher D Porada
The stem cell compartment of the hematopoietic system constitutes one of the most radiosensitive tissues of the body and leukemias represent one of the most frequent radiogenic cancers with short latency periods. As such, leukemias may pose a particular threat to astronauts during prolonged space missions. Control of hematopoiesis is tightly governed by a specialized bone marrow (BM) microenvironment/niche. As such, any environmental insult that damages cells of this niche would be expected to produce pronounced effects on the types and functionality of hematopoietic/immune cells generated...
April 26, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29685144/emerging-roles-of-epithelial-mesenchymal-transition-in-hematological-malignancies
#16
REVIEW
San-Chi Chen, Tsai-Tsen Liao, Muh-Hwa Yang
BACKGROUND: Epithelial-mesenchymal transition is an important process in embryonic development, fibrosis, and cancer metastasis. During the progression of epithelial cancer, activation of epithelial-mesenchymal transition is tightly associated with metastasis, stemness and drug resistance. However, the role of epithelial-mesenchymal transition in non-epithelial cancer is relatively unclear. MAIN BODY: Epithelial-mesenchymal transition transcription factors are critical in both myeloid and lymphoid development...
April 23, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29683733/cep55-overexpression-causes-male-specific-sterility-in-mice-by-suppressing-foxo1-nuclear-retention-through-sustained-activation-of-pi3k-akt-signaling
#17
Debottam Sinha, Murugan Kalimutho, Josephine Bowles, Ai-Leen Chan, D Jo Merriner, Amanda L Bain, Jacinta L Simmons, Raimundo Freire, J Alejandro Lopez, Robin M Hobbs, Moira K O'Bryan, Kum Kum Khanna
Spermatogenesis is a dynamic process involving self-renewal and differentiation of spermatogonial stem cells, meiosis, and ultimately, the differentiation of haploid spermatids into sperm. Centrosomal protein (CEP)-55 is necessary for somatic cell abscission during cytokinesis. It facilitates equal segregation of cytoplasmic contents between daughter cells by recruiting endosomal sorting complex required for transport machinery (ESCRT) at the midbody. In germ cells, CEP55, in partnership with testes expressed-14 protein (TEX14), has also been shown to be an integral component of intercellular bridge before meiosis...
April 17, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29682980/aging-and-senescence-associated-changes-of-mesenchymal-stromal-cells-in-myelodysplastic-syndromes
#18
Domenico Mattiucci, Giulia Maurizi, Pietro Leoni, Antonella Poloni
Hematopoietic stem and progenitor cells reside within the bone marrow (BM) microenvironment. By a well-balanced interplay between self-renewal and differentiation, they ensure a lifelong supply of mature blood cells. Physiologically, multiple different cell types contribute to the regulation of stem and progenitor cells in the BM microenvironment by cell-extrinsic and cell-intrinsic mechanisms. During the last decades, mesenchymal stromal cells (MSCs) have been identified as one of the main cellular components of the BM microenvironment holding an indispensable role for normal hematopoiesis...
January 1, 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29678688/control-in-dormancy-or-eradication-of-cancer-stem-cells-mathematical-modeling-and-stability-issues
#19
Walid Djema, Catherine Bonnet, Frédéric Mazenc, Jean Clairambault, Emilia Fridman, Pierre Hirsch, François Delhommeau
OBJECTIVE: Modeling and analysis of cell population dynamics enhance our understanding of cancer. Here we introduce and explore a new model that may apply to many tissues. ANALYSES: An age-structured model describing coexistence between mutated and ordinary stem cells is developed and explored. The model is transformed into a nonlinear time-delay system governing the dynamics of healthy cells, coupled to a nonlinear differential-difference system describing dynamics of unhealthy cells...
April 17, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29656660/cytotoxic-flavonoids-from-two-lonchocarpus-species
#20
Fozia A Adem, Victor Kuete, Armelle T Mbaveng, Matthias Heydenreich, Andreas Koch, Albert Ndakala, Beatrice Irungu, Abiy Yenesew, Thomas Efferth
A new isoflavone, 4'-prenyloxyvigvexin A (1) and a new pterocarpan, (6aR,11aR)-3,8-dimethoxybitucarpin B (2) were isolated from the leaves of Lonchocarpus bussei and the stem bark of Lonchocarpus eriocalyx, respectively. The extract of L. bussei also gave four known isoflavones, maximaisoflavone H, 7,2'-dimethoxy-3',4'-methylenedioxyisoflavone, 6,7,3'-trimethoxy-4',5'-methylenedioxyisoflavone, durmillone; a chalcone, 4-hydroxylonchocarpin; a geranylated phenylpropanol, colenemol; and two known pterocarpans, (6aR,11aR)-maackiain and (6aR,11aR)-edunol...
April 16, 2018: Natural Product Research
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