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Mariko Yabe, L Jeffrey Medeiros, Sa A Wang, Guilin Tang, Carlos E Bueso-Ramos, Jeffrey L Jorgensen, Govind Bhagat, Weina Chen, Shaoying Li, Ken H Young, Roberto N Miranda
Hepatosplenic T-cell lymphoma (HSTCL) is a rare, aggressive T-cell lymphoma that can be challenging to diagnose. In particular, distinguishing HSTCL from T-cell large granular lymphocytic (T-LGL) leukemia of γδ T-cell receptor (TCR) type is difficult without examination of a splenectomy specimen. In this study, we systematically assessed a series of HSTCL cases for findings reported in the literature as supporting or not supporting the diagnosis of HSTCL. We also compared HSTCL with a group of cases of T-LGL of γδ TCR type...
October 13, 2016: American Journal of Surgical Pathology
Ilaria Visco, Carsten Hoege, Anthony A Hyman, Petra Schwille
Cell polarity arises from a combination of interactions between biological molecules, such as activation, inhibition, and positive or negative feedback between specific polarity units. Activation and inhibition often take place in the form of a membrane binding switch. Lethal Giant Larvae (LGL), a conserved regulator of cell polarity in animals, was suggested to function as such a switch. LGL localizes both to the cytoplasm and, asymmetrically, to the membrane. However, the spatial regulation mechanism of LGL membrane localization has remained unclear...
October 6, 2016: Journal of Molecular Biology
Kristine C Olson, Paige M Kulling, Thomas L Olson, Su-Fern Tan, Rebecca J Rainbow, David J Feith, Thomas P Loughran
Large granular lymphocyte leukemia (LGLL) is a rare incurable chronic disease typically characterized by clonal expansion of CD3+ cytotoxic T-cells. Two signal transducer and activator of transcription factors, STAT1 and STAT3, are constitutively active in T-LGLL. Disruption of this activation induces apoptosis in T-LGLL cells. Therefore, considerable efforts are focused on developing treatments that inhibit STAT activation. Calcitriol, the active form of vitamin D, has been shown to decrease STAT1 and STAT3 phosphorylation in cancer cell lines and autoimmune disease mouse models...
October 7, 2016: Cancer Biology & Therapy
Takahiro Tanahashi, Nodoka Sekiguchi, Kazuyuki Matsuda, Akihiro Matsumoto, Toshiro Ito, Hideyuki Nakazawa, Fumihiro Ishida
Large granular lymphocyte leukemia (LGL-L) is defined morphologically as a group of lymphoproliferative disorders, including T-cell large granular lymphocytic leukemia (T-LGL-L), chronic lymphoproliferative disorders of NK cells (CLPD-NK), and aggressive NK cell leukemia. We investigated the morphological features of LGL leukemic cells in LGL-L patients to identify screening methods best suited to application in daily clinical practice. LGL leukemic cells were mostly indistinguishable from normal LGL; however, we developed a simplified approach to distinguishing among these cells, in which lymphocyte  % and the proportion of granular lymphocytes among lymphocytes (GL %) can serve as parameters at the cut-off values of 52 and 50 %, respectively...
September 29, 2016: International Journal of Hematology
Santosh Kumar Yadav, Indrasen Magre, Aditi Singh, Deepak Khuperkar, Jomon Joseph
Atypical PKC (aPKC) family members are involved in regulation of diverse cellular processes, including cell polarization. aPKCs are known to be activated by phosphorylation of specific threonine residues in the activation loop and turn motif. They can also be stimulated by interaction with Cdc42~GTP-Par6 complex. Here we report that PKCζ, a member of the aPKC family, is activated by SUMOylation. We show that aPKC is endogenously modified by SUMO1 and the nucleoporin Nup358 acts as its SUMO E3 ligase. Results from in vitro SUMOylation and kinase assays showed that the modification enhances the kinase activity of PKCζ by ~10-fold...
September 29, 2016: Scientific Reports
Talha Munir, Mark J Bishton, Ian Carter, Andrew McMillan, Simon O'Connor, Vishakha Sovani, Andrew P Haynes, Christopher P Fox
INTRODUCTION: Large granular lymphocyte (LGL) leukemia is a rare chronic lymphoproliferative disorder, with few large series reported to date. Series using stringent diagnostic criteria incorporating bone marrow biopsy (BMB), immunophenotyping, and T-cell receptor rearrangements are even scarcer. PATIENTS AND METHODS: The present study was a single-center series of 39 patients with LGL leukemia diagnosed using immunohistochemical analysis of BMB samples and flow cytometric and molecular data...
August 10, 2016: Clinical Lymphoma, Myeloma & Leukemia
Selma Waaijers, Javier Muñoz, Christian Berends, João J Ramalho, Soenita S Goerdayal, Teck Y Low, Adja D Zoumaro-Djayoon, Michael Hoffmann, Thijs Koorman, Roderick P Tas, Martin Harterink, Stefanie Seelk, Jana Kerver, Casper C Hoogenraad, Olaf Bossinger, Baris Tursun, Sander van den Heuvel, Albert J R Heck, Mike Boxem
BACKGROUND: Affinity purification followed by mass spectrometry (AP/MS) is a widely used approach to identify protein interactions and complexes. In multicellular organisms, the accurate identification of protein complexes by AP/MS is complicated by the potential heterogeneity of complexes in different tissues. Here, we present an in vivo biotinylation-based approach for the tissue-specific purification of protein complexes from Caenorhabditis elegans. Tissue-specific biotinylation is achieved by the expression in select tissues of the bacterial biotin ligase BirA, which biotinylates proteins tagged with the Avi peptide...
2016: BMC Biology
Juliana E Hidalgo Lopez, Mariko Yabe, Adrian A Carballo-Zarate, Sa A Wang, Jeffrey L Jorgensen, Sairah Ahmed, John Lee, Shaoying Li, Ellen Schlette, Timothy McDonnell, Roberto N Miranda, L Jeffrey Medeiros, Carlos E Bueso-Ramos, C Cameron Yin
T-cell large granular lymphocytic (T-LGL) leukemia after hematopoietic stem cell transplantation (SCT) is rare and its natural history and clinical outcome have not been well described. We report the clinical, morphologic, immunophenotypic, and molecular features of a case of donor-derived T-LGL leukemia in a 16-year-old man who received allogeneic SCT for peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). The patient presented with persistent neutropenia and splenomegaly 9 months after SCT when the chimerism study showed a 100% donor pattern...
August 2016: Journal of the National Comprehensive Cancer Network: JNCCN
M V Shah, C C Hook, T G Call, R S Go
Large granular lymphocyte (LGL) leukemia is a lymphoproliferative disorder of cytotoxic cells. T-cell LGL (T-LGL) leukemia is characterized by accumulation of cytotoxic T cells in blood and infiltration of the bone marrow, liver or spleen. Population-based studies have not been reported in LGL leukemia. We present clinical characteristics, natural history and risk factors for poor survival in patients with LGL leukemia using the Surveillance, Epidemiology, and End Results Program (SEER) and the United States National Cancer Data Base (NCDB)...
2016: Blood Cancer Journal
Gregory V Schimizzi, Meghan T Maher, Andrew J Loza, Gregory D Longmore
The establishment and maintenance of apical-basal polarity is a defining characteristic and essential feature of functioning epithelia. Apical-basal polarity (ABP) proteins are also tumor suppressors that are targeted for disruption by oncogenic viruses and are commonly mutated in human carcinomas. Disruption of these ABP proteins is an early event in cancer development that results in increased proliferation and epithelial disorganization through means not fully characterized. Using the proliferating Drosophila melanogaster wing disc epithelium, we demonstrate that disruption of the junctional vs...
2016: PloS One
Sergio Casas-Tintó, Antonio Maraver, Manuel Serrano, Alberto Ferrús
Human tumors of various tissue origins show an intriguing over-expression of genes not considered oncogenes, such as that encoding Troponin-I (TnI), a well-known muscle protein. Out of the three TnI genes known in humans, the slow form, TNNI1, is affected the most. Drosophila has only one TnI gene, wupA. Here, we studied excess- and loss-of function of wupA in Drosophila, and assayed TNNI1 down regulation in human tumors growing in mice. Drosophila TnI excess-of-function increases proliferation and potentiates oncogenic mutations in Ras, Notch and Lgl genes...
July 15, 2016: Oncotarget
Di Wu, Guoyuan Liu, Yufeng Liu, Hexige Saiyin, Chenji Wang, Zhen Wei, Wenjiao Zen, Danyang Liu, Qi Chen, Zhonghua Zhao, Liping Zou, Haojie Huang, Songmin Jiang, Long Yu
UNLABELLED: Interplay between cell polarity module Scribble-Lethal Giant Larvae-Discs Large 1 (DLG1) and Yes-associated protein (YAP) appears critical in tumor metastasis. We identified zinc finger protein 191 (ZNF191) as a metastasis suppressor acting through DLG-YAP crosstalk in hepatocellular carcinoma (HCC). Overexpression of ZNF191 in HCC cells impaired cell motility, while ZNF191 depletion promoted cell migration in vitro and metastasis in vivo through triggering YAP signaling. Chromatin immunoprecipitation-sequencing revealed that ZNF191 specifically bound to the promoter of DLG1, a cell polarity maintainer and a negative regulator of YAP...
October 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Taiki Mori, Yusuke Murasawa, Rina Ikai, Tomoko Hayakawa, Hiroyuki Nakamura, Noboru Ogiso, Shumpei Niida, Ken Watanabe
IL-6 is a cytokine that is involved in various physiological and pathological conditions, and approaches using gain-of-function transgenic animals have contributed in elucidating IL-6 function. However, studies of the multiple functions of IL-6 in vivo are very time consuming because they require the generation of transgenic mice that harbor the gene encoding IL-6 under the control of specific promoters to mimic different pathologies. Here, we report the establishment of a conditional human IL-6 transgenic mouse, LGL-IL6, which conditionally expresses human IL-6 by taking advantage of the well-characterized Cre recombinase drivers...
June 28, 2016: Experimental Animals
Robert R Maronpot, Abraham Nyska, Jennifer E Foreman, Yuval Ramot
The Fischer 344 (F344) rat was used by the National Toxicology Program (NTP) for over 5 decades for toxicity and carcinogenicity studies. However, in 2006, the NTP decided to switch to a different rat stock due largely to high background control incidences of Leydig cell tumors (LCTs) and mononuclear cell leukemia (MNCL), also known as large granular lymphocytic (LGL) leukemia. In the current review, we aim (1) to provide a summary of NTP bioassays with treatment-associated effects involving MNCL and LCTs in addition to male F344-specific tunica vaginalis mesothelioma (TVM); (2) to describe important pathobiological differences between these F344 rat tumor responses and similar target tissue-tumor response in humans; and (3) to present the NTP reasons for switching away from the F344 rat...
September 2016: Critical Reviews in Toxicology
Renuka Raman, Indraneel Damle, Rahul Rote, Shamik Banerjee, Chaitanya Dingare, Mahendra Sonawane
Epithelial cells exhibit apical membrane protrusions, which confer specific functions to epithelial tissues. Microridges are short actin protrusions that are laterally long and form a maze-like pattern in the apical domain. They are widely found on vertebrate squamous epithelia including epidermis and have functions in mucous retention, membrane storage and abrasion resistance. It is largely unknown how the formation of these laterally long actin projections is regulated. Here, we show that antagonistic interactions between aPKC and Lgl-regulators of apical and basolateral domain identity, respectively,-control the length of microridges in the zebrafish periderm, the outermost layer of the epidermis...
2016: Nature Communications
Manuel Calleja, Ginés Morata, Jordi Casanova
BACKGROUND: Mutations in Drosophila tumor suppressor genes (TSGs) lead to the formation of invasive tumors in the brain and imaginal discs. RESULTS: Here we studied the tumorigenic properties of imaginal discs mutant for the TSG gene lethal giant larvae (lgl). lgl mutant cells display the characteristic features of mammalian tumor cells: they can proliferate indefinitely, induce additional tracheogenesis (an insect counterpart of vasculogenesis) and invade neighboring tissues...
August 2016: Developmental Dynamics: An Official Publication of the American Association of Anatomists
M H Alzawqari, A A Al-Baddany, H H Al-Baadani, I A Alhidary, Rifat Ullah Khan, G M Aqil, A Abdurab
The current experiment was conducted to evaluate the effects of feeding dried sweet orange peel (SOP) and lemon grass leaves (LGL) as feed additives on broiler growth performance, serum metabolites, and antioxidant status. A total of 192-day-old (Ross 308) broiler chickens were distributed randomly into 4 dietary treatments with 4 replicates per each treatment. The dietary treatments included a control diet without any feed additive (T1), a diet containing 0.8 % SOP (T2), a diet containing 0.8 % LGL (T3), and a diet containing combination of 0...
September 2016: Environmental Science and Pollution Research International
Sybille Koehler, Frederik Tellkamp, Carien M Niessen, Wilhelm Bloch, Dontscho Kerjaschki, Bernhard Schermer, Thomas Benzing, Paul T Brinkkoetter
Polarity signaling through the atypical PKC (aPKC)-Par polarity complex is essential for the development and maintenance of the podocyte architecture and the function of the glomerular filtration barrier of the kidney. To study the contribution of Par3A in this complex, we generated a novel Pard3 podocyte-specific knockout mouse model by targeting exon 6 of the Pard3 gene. Genetic deletion of Pard3a did not impair renal function, neither at birth nor later in life. Even challenging the animals did not result in glomerular disease...
July 1, 2016: American Journal of Physiology. Renal Physiology
S Kolb, S Hörmansdorfer, N Ackermann, C Höller, B Brenner, C Herr
Employees and volunteers often feel insecure about the potential transmission of infectious diseases when taking care of asylum seekers. It could be shown that overall only a minor risk of infection emanates from asylum seekers. However, aspects of occupational health and vaccination should be kept in mind.Besides the standard vaccination the Standing Committee on Vaccination (STIKO) recommends for occupational indication, which is given for employees and volunteers in asylum facilities, vaccination against hepatitis A, hepatitis B, polio (if the last vaccination was more than 10 years before) as well as influenza (seasonal)...
April 2016: Das Gesundheitswesen
Michitoshi Hashiguchi, Takashi Okamura, Kei Nomura, Takayuki Nakamura, Kuniki Kawaguchi, Satoko Koteda, Satoshi Morishige, Eijirou Oku, Yuka Takata, Ritsuko Seki, Fumihiko Mouri, Koichi Osaki, Kohji Yoshimoto, Yutaka Imamura, Koji Nagafuji
A 72-year-old Japanese male was diagnosed as having monoclonal gammopathy of undetermined significance and was followed up without therapy. Three years later, the patient progressed to symptomatic multiple myeloma. Melphalan + prednisolone was administered as first-line chemotherapy for ~6 years. Since the patient was judged to exhibit refractory multiple myeloma, he subsequently received radiation therapy on the lumbar spine. The patient was enrolled in a clinical trial and received lenalidomide + lowdose dexamethasone (Rd) therapy...
April 2016: Molecular and Clinical Oncology
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