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https://www.readbyqxmd.com/read/28212447/diffuse-large-b-cell-lymphoma-with-concurrent-high-myc-and-bcl2-expression-shows-evidence-of-active-b-cell-receptor-signaling-by-quantitative-immunofluorescence
#1
Agata M Bogusz, Alexandra E Kovach, Long P Le, Derek Feng, Richard H G Baxter, Aliyah R Sohani
B-cell receptor (BCR)-mediated signaling plays an important role in the pathogenesis of a subset of diffuse large B-cell lymphoma (DLBCL), and novel agents targeting this pathway are now in clinical use. We have previously identified a signature of active BCR signaling on formalin-fixed paraffin-embedded specimens using quantitative immunofluorescence, allowing for identification of patients who might benefit from anti-BCR therapies. We sought to characterize the clinicopathologic significance of active BCR signaling in DLBCL by correlating measures of signaling intensity with clinical features and various tumor cell characteristics...
2017: PloS One
https://www.readbyqxmd.com/read/28212321/therapeutic-approaches-targeting-myc-driven-prostate-cancer
#2
REVIEW
Richard J Rebello, Richard B Pearson, Ross D Hannan, Luc Furic
The transcript encoding the proto-oncogene MYC is commonly overexpressed in prostate cancer (PC). MYC protein abundance is also increased in the majority of cases of advanced and metastatic castrate-resistant PC (mCRPC). Accordingly, the MYC-directed transcriptional program directly contributes to PC by upregulating the expression of a number of pro-tumorigenic factors involved in cell growth and proliferation. A key cellular process downstream of MYC activity is the regulation of ribosome biogenesis which sustains tumor growth...
February 16, 2017: Genes
https://www.readbyqxmd.com/read/28211508/mvp-mediated-exosomal-sorting-of-mir-193a-promotes-colon-cancer-progression
#3
Yun Teng, Yi Ren, Xin Hu, Jingyao Mu, Abhilash Samykutty, Xiaoying Zhuang, Zhongbin Deng, Anil Kumar, Lifeng Zhang, Michael L Merchant, Jun Yan, Donald M Miller, Huang-Ge Zhang
Exosomes are emerging mediators of intercellular communication; whether the release of exosomes has an effect on the exosome donor cells in addition to the recipient cells has not been investigated to any extent. Here, we examine different exosomal miRNA expression profiles in primary mouse colon tumour, liver metastasis of colon cancer and naive colon tissues. In more advanced disease, higher levels of tumour suppressor miRNAs are encapsulated in the exosomes. miR-193a interacts with major vault protein (MVP)...
February 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28211476/novel-roles-for-staufen1-in-embryonal-and-alveolar-rhabdomyosarcoma-via-c-myc-dependent-and-independent-events
#4
Tara E Crawford Parks, Kristen A Marcellus, Jonathan Langill, Aymeric Ravel-Chapuis, Jean Michaud, Kyle N Cowan, Jocelyn Côté, Bernard J Jasmin
Rhabdomyosarcoma is the most common soft tissue sarcoma in children and young adults. Rhabdomyosarcomas are skeletal muscle-like tumours that typically arise in muscle beds, and express key myogenic regulatory factors. However, their developmental program remains blocked in the proliferative phase with cells unable to exit the cell cycle to fuse into myotubes. Recently, we uncovered a key role for the RNA-binding protein Staufen1 during myogenic differentiation through the regulation of c-myc translation. Given the known implication of c-myc in rhabdomyosarcoma, we hypothesized in the current work that Staufen1 controls rhabdomyosarcoma tumorigenesis...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209658/relevance-of-id3-tcf3-ccnd3-pathway-mutations-in-pediatric-aggressive-b-cell-lymphoma-treated-according-to-the-nhl-bfm-protocols
#5
Marius Rohde, Bettina R Bonn, Martin Zimmermann, Jonas Lange, Anja Möricke, Wolfram Klapper, Ilske Oschlies, Monika Szczepanowski, Inga Nagel, Martin Schrappe, Markus Loeffler, Reiner Siebert, Alfred Reiter, Birgit Burkhardt
Mature B-cell Non-Hodgkin lymphoma is the most common subtype of Non-Hodgkin lymphoma in childhood and adolescence. B-cell Non-Hodgkin lymphoma are further classified into histological subtypes, with Burkitt lymphoma and Diffuse large B-cell lymphoma being the most common subgroups in pediatric patients. Translocations involving the MYC oncogene are known as relevant but not sufficient hit for Burkitt lymphoma pathogenesis. Recently published large-scale next-generation sequencing studies unveiled sets of additional recurrently mutated genes in samples of pediatric and adult B-cell Non-Hodgkin lymphoma patients...
February 16, 2017: Haematologica
https://www.readbyqxmd.com/read/28209620/the-histone-methyltransferase-dot1l-promotes-neuroblastoma-by-regulating-gene-transcription
#6
Matthew Wong, Andrew El Tee, Giorgio Milazzo, Jessica L Bell, Rebecca C Poulos, Bernard Atmadibrata, Yuting Sun, Duohui Jing, Nicholas Ho, Dora Ling, Pei Yan Liu, Xu Dong Zhang, Stefan Hüttelmaier, Jason W H Wong, Jenny Wang, Patsie Polly, Giovanni Perini, Christopher J Scarlett, Tao Liu
Myc oncoproteins exert tumorigenic effects by regulating expression of target oncogenes. Histone H3 lysine 79 (H3K79) methylation at Myc-responsive elements of target gene promoters is a strict prerequisite for Myc-induced transcriptional activation, and DOT1L is the only known histone methyltransferase that catalyses H3K79 methylation. Here we show that N-Myc upregulatsd DOT1L mRNA and protein expression by binding to the DOT1L gene promoter. shRNA-mediated depletion of DOT1L reduced mRNA and protein expression of N-Myc target genes ODC1 and E2F2...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28209530/slc39a6-promotes-aggressiveness-of-esophageal-carcinoma-cells-by-increasing-intracellular-levels-of-zinc-activating-phosphatidylinositol-3-kinase-signaling-and-upregulating-genes-that-regulate-metastasis
#7
Xinxin Cheng, Lixuan Wei, Xudong Huang, Jian Zheng, Mingming Shao, Ting Feng, Jun Li, Yaling Han, Wenle Tan, Wen Tan, Dongxin Lin, Chen Wu
BACKGROUND & AIMS: A common variant in the solute carrier family 39 member 6 gene (SLC39A6) has been associated with survival times of patients with esophageal squamous-cell carcinoma (ESCC). We investigated the function of SLC39A6 and ways in which this variant affects tumor progression by studying ESCC samples and cell lines. METHODS: SLC39A6 was expressed, or knocked down by expression of small hairpin RNAs, in ESCC cells (KYSE30 and KYSE450) and HeLa cells using lentiviral vectors; we analyzed effects on proliferation, colony formation, migration, and invasion in vitro...
February 13, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28209368/correlation-of-micro-vessel-density-and-c-myc-expression-in-breast-tumor-of-mice-following-mesenchymal-stem-cell-therapy
#8
Maryam Adelipour, Fatemeh Babaei, Mohammadreza Mirzababaei, Abdolamir Allameh
Stem cell therapy for degenerative diseases has been established; however there are controversies over the treatment of solid tumors with stem cell transplantation. In the present study, the anti-tumor action of mesenchymal stem cells (MSCs) has been examined in a mouse model of breast cancer with emphasize on tumor growth, angiogenesis and c-Myc expression in breast tumors. For this purpose, MSCs were isolated from bone marrow of Balb/c mice and characterized. A Balb/c mouse model of breast cancer was developed and subjected to cell therapy intra venous (I...
January 30, 2017: Tissue & Cell
https://www.readbyqxmd.com/read/28209136/bcl-2-and-myc-gain-amplification-is-correlated-with-central-nervous-system-involvement-in-diffuse-large-b-cell-lymphoma-at-leukemic-phase
#9
Dehui Zou, Shuhua Yi, Rui Cui, Wei Liu, Chengwen Li, Shizhen Zhong, Zhen Yu, Zengjun Li, Rui Lv, Kun Ru, Huijun Wang, Gang An, Yan Xu, Lugui Qiu
BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) of leukemic phase is a rare clinical manifestation, but is highly prevalent with central nervous system involvement (CNSI). Little is known about this rare clinical observation. METHODS: We reviewed the clinical characteristics of 40 DLBCL patients with leukemic phase identified by flow cytometry and analyzed BCL2 and MYC aberrations by fluorescence in situ hybridization. RESULTS: The median age of these 40 patients was 46 years (range, 15-75) with 19 men patients...
February 16, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28205554/the-oncoppi-network-of-cancer-focused-protein-protein-interactions-to-inform-biological-insights-and-therapeutic-strategies
#10
Zenggang Li, Andrei A Ivanov, Rina Su, Valentina Gonzalez-Pecchi, Qi Qi, Songlin Liu, Philip Webber, Elizabeth McMillan, Lauren Rusnak, Cau Pham, Xiaoqian Chen, Xiulei Mo, Brian Revennaugh, Wei Zhou, Adam Marcus, Sahar Harati, Xiang Chen, Margaret A Johns, Michael A White, Carlos Moreno, Lee A D Cooper, Yuhong Du, Fadlo R Khuri, Haian Fu
As genomics advances reveal the cancer gene landscape, a daunting task is to understand how these genes contribute to dysregulated oncogenic pathways. Integration of cancer genes into networks offers opportunities to reveal protein-protein interactions (PPIs) with functional and therapeutic significance. Here, we report the generation of a cancer-focused PPI network, termed OncoPPi, and identification of >260 cancer-associated PPIs not in other large-scale interactomes. PPI hubs reveal new regulatory mechanisms for cancer genes like MYC, STK11, RASSF1 and CDK4...
February 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28205547/microrna-17-family-promotes-polycystic-kidney-disease-progression-through-modulation-of-mitochondrial-metabolism
#11
Sachin Hajarnis, Ronak Lakhia, Matanel Yheskel, Darren Williams, Mehran Sorourian, Xueqing Liu, Karam Aboudehen, Shanrong Zhang, Kara Kersjes, Ryan Galasso, Jian Li, Vivek Kaimal, Steven Lockton, Scott Davis, Andrea Flaten, Joshua A Johnson, William L Holland, Christine M Kusminski, Philipp E Scherer, Peter C Harris, Marie Trudel, Darren P Wallace, Peter Igarashi, Edmund C Lee, John R Androsavich, Vishal Patel
Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent genetic cause of renal failure. Here we identify miR-17 as a target for the treatment of ADPKD. We report that miR-17 is induced in kidney cysts of mouse and human ADPKD. Genetic deletion of the miR-17∼92 cluster inhibits cyst proliferation and PKD progression in four orthologous, including two long-lived, mouse models of ADPKD. Anti-miR-17 treatment attenuates cyst growth in short-term and long-term PKD mouse models. miR-17 inhibition also suppresses proliferation and cyst growth of primary ADPKD cysts cultures derived from multiple human donors...
February 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28203109/a-b-cell-lymphoma-case-that-is-unclassifiable-and-intermediate-between-diffuse-large-b-cell-lymphoma-and-burkitt-lymphoma-of-lacrimal-gland
#12
Tatsuya Yunoki, Jun Murakami, Yukihiro Imagawa, Takahiko Nakajima, Atsushi Hayashi
A 60-year-old woman presented with acute eyelid swelling and a subcutaneous hemorrhage in the right eye. Magnetic resonance imaging showed a spherical tumor of the lacrimal gland. The tumor was removed by the Kroenlein method. We diagnosed as a B-cell lymphoma that is unclassifiable, and intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL) (intermediate DLBCL/BL) based on its immunohistopathological examination and c-MYC/IgH rearrangement. We administered six cycles of dose-adjusted-EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin hydrochloride, and rituximab) therapy, and remission of the lymphoma was obtained...
2017: International Medical Case Reports Journal
https://www.readbyqxmd.com/read/28202850/hypermethylation-of-the-n-myc-downstream-regulated-gene-2-promoter-in-peripheral-blood-mononuclear-cells-is-associated-with-liver-fibrosis-in-chronic-hepatitis-b
#13
Xin-Yuan Liu, Yu-Chen Fan, Shuai Gao, Jing Zhao, Feng Li, Jun Zhang, Kai Wang
DNA methylation is a fundamental epigenetic modification to regulate gene expression. N-Myc downstream-regulated gene (NDRG) 2 is a cytoplasmic protein and participates in the pathogenesis of liver fibrosis. In this study, the mRNA expression and methylation status of NDRG2 was evaluated in patients with chronic hepatitis B (CHB). The study included 143 CHB patients and 65 normal controls (NC). The mRNA expression of NDRG2 in peripheral blood mononuclear cells (PBMCs) was detected by quantitative real-time polymerase chain reaction...
2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28202516/modeling-the-genetic-regulation-of-cancer-metabolism-interplay-between-glycolysis-and-oxidative-phosphorylation
#14
Linglin Yu, Mingyang Lu, Dongya Jia, Jianpeng Ma, Eshel Ben-Jacob, Herbert Levine, Benny A Kaipparettu, Jose' N Onuchic
Abnormal metabolism is a hallmark of cancer, yet its regulation remains poorly understood. Cancer cells were considered to utilize primarily glycolysis for ATP production, referred to as the Warburg effect. However, recent evidence suggests that oxidative phosphorylation (OXPHOS) plays a crucial role during cancer progression. Here we utilized a systems biology approach to decipher the regulatory principle of glycolysis and OXPHOS. Integrating information from literature, we constructed a regulatory network of genes and metabolites from which we extracted a core circuit containing HIF-1, AMPK, and ROS...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28202510/myc-mediates-large-oncosome-induced-fibroblast-reprogramming-in-prostate-cancer
#15
Valentina R Minciacchi, Cristiana Spinelli, Mariana Reis-Sobreiro, Lorenzo Cavallini, Sungyong You, Mandana Zandian, Xiaohong Li, Paola Chiarugi, Rosalyn M Adam, Edwin M Posadas, Giuseppe Viglietto, Michael R Freeman, Emanuele Cocucci, Neil A Bhowmick, Dolores Di Vizio
Communication between cancer cells and the tumor microenvironment results in the modulation of complex signaling networks that facilitate tumor progression. Here we describe a new mechanism of intercellular communication originating from large oncosomes (LO), which are cancer cell-derived, atypically large (1-10 μm) extracellular vesicles (EV). We demonstrate that, in the context of prostate cancer, LO harbor sustained AKT1 kinase activity, nominating them as active signaling platforms. Active AKT1 was detected in circulating EV from the plasma of metastatic prostate cancer patients and was LO specific...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28202458/sensitivity-to-pi3k-and-akt-inhibitors-is-mediated-by-divergent-molecular-mechanisms-in-subtypes-of-dlbcl
#16
Tabea Erdmann, Pavel Klener, James T Lynch, Michael Grau, Petra Vočková, Jan Molinsky, Diana Tuskova, Kevin Hudson, Urszula M Polanska, Michael Grondine, Michele Mayo, Beiying Dai, Matthias Pfeifer, Kristian Erdmann, Daniela Schwammbach, Myroslav Zapukhlyak, Annette M Staiger, German Ott, Wolfgang E Berdel, Barry R Davies, Francisco Cruzalegui, Marek Trneny, Peter Lenz, Simon T Barry, Georg Lenz
Activated B-cell-like (ABC) and germinal center B-cell-like (GCB) diffuse large B-cell lymphoma (DLBCL) represent the two major molecular DLBCL subtypes. They are characterized by differences in clinical course and by divergent addiction to oncogenic pathways. To determine activity of novel compounds in these two subtypes, we conducted an unbiased pharmacologic in vitro screen. The phosphatidylinositol-3-kinase (PI3K) alpha/delta (PI3Kα/δ) inhibitor AZD8835 showed marked potency in ABC DLBCL models, whereas the protein kinase B (AKT) inhibitor AZD5363 induced apoptosis in PTEN-deficient DLBCLs irrespective of their molecular subtype...
February 15, 2017: Blood
https://www.readbyqxmd.com/read/28196804/nipped-a-regulates-intestinal-stem-cell-proliferation-in-drosophila
#17
Helen Marie Tauc, Alpaslan Tasdogan, Patrick Meyer, Petra Pandur
Adult stem cells uphold a delicate balance between quiescent and active states, a deregulation of which can lead to age-associated diseases such as cancer. In Drosophila, intestinal stem cell (ISC) proliferation is tightly regulated and mis-regulation is detrimental to intestinal homeostasis. Various factors are known to govern ISC behavior; however, transcriptional changes in ISCs during aging are still unclear. RNA sequencing of young and old ISCs newly identified Nipped-A, a subunit of histone acetyltransferase complexes, as a regulator of ISC proliferation that is upregulated in old ISCs...
February 15, 2017: Development
https://www.readbyqxmd.com/read/28196286/psoralen-with-ultraviolet-a-puva-induced-apoptosis-of-cutaneous-lymphoma-cell-lines-is-augmented-by-type-i-interferons-via-the-jak1-stat1-pathway
#18
Walter Liszewski, David Gram Naym, Edyta Biskup, Robert Gniadecki
BACKGROUND: Photochemotherapy with psoralen and ultraviolet A (PUVA), with or without adjuvant interferon-α (IFN-α), is a first line therapy for early stage mycosis fungoides and other forms of cutaneous T-cell lymphoma (CTCL). However, the mechanism by which PUVA with IFN-α work in CTCL is poorly understood. PURPOSE: To develop a model to investigate the mechanisms of PUVA and PUVA with IFN-α in CTCL cells. METHODS: An in vitro model to study the molecular mechanisms of PUVA was created using two different CTCL cell lines, MyLa, which has functional p53, and HuT-78, in which p53 is inactivated due to a homozygous nonsense mutation...
February 14, 2017: Photodermatology, Photoimmunology & Photomedicine
https://www.readbyqxmd.com/read/28195879/fibrin-associated-ebv-positive-large-b-cell-lymphoma-an-indolent-neoplasm-with-features-distinct-from-diffuse-large-b-cell-lymphoma-associated-with-chronic-inflammation
#19
Daniel F Boyer, Penelope A McKelvie, Laurence de Leval, Kerstin L Edlefsen, Young-Hyeh Ko, Zachary A Aberman, Alexandra E Kovach, Aneal Masih, Ha T Nishino, Lawrence M Weiss, Alan K Meeker, Valentina Nardi, Maryknoll Palisoc, Lina Shao, Stefania Pittaluga, Judith A Ferry, Nancy Lee Harris, Aliyah R Sohani
Incidental cases of localized fibrin-associated Epstein-Barr virus (EBV)+ large B-cell proliferations have been described at unusual anatomic sites and have been included in the category of diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI) in the WHO Classification. We describe 12 cases and review the literature to define their clinicopathologic spectrum and compare features with typical cases of DLBCL-CI. Median age was 55.5 years with a M:F ratio of 3. In all 12 cases, the lymphoma was an incidental microscopic finding involving atrial myxomas (n=3), thrombi associated with endovascular grafts (n=3), chronic hematomas (n=2), and pseudocysts (n=4)...
March 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28193566/in-vitro-evaluation-of-ruthenium-complexes-for-photodynamic-therapy
#20
Wenna Li, Qiang Xie, Linglin Lai, Zhentao Mo, Xiaofang Peng, Ennian Leng, Dandan Zhang, Hongxia Sun, Yiqi Li, Wenjie Mei, Shuying Gao
BACKGROUND: Photodynamic therapy (PDT) is a promising new anti-tumor treatment strategy. Photosensitizer is one of the most important components of PDT. In this work, the anticancer activities of PDTs mediated by six new ruthenium porphyrin complexes were screened. The mechanisms of the most efficacious candidate were investigated. METHODS: Photocytotoxicity of the six porphyrins was tested. The most promising complex, Rup-03, was further investigated using Geimsa staining, which indirectly detects reactive oxygen species (ROS) and subcellular localization...
February 10, 2017: Photodiagnosis and Photodynamic Therapy
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