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https://www.readbyqxmd.com/read/28988442/dramatic-response-to-nivolumab-in-xeroderma-pigmentosum-skin-tumor
#1
Fanny Chambon, Sophie Osdoit, Kelly Bagny, Anne Moro, Jacqueline Nguyen, Yves Réguerre
We report the case of a 6-year-old female with xeroderma pigmentosum (XP) who developed a nonoperable scalp tumor, treated with anti-programmed cell death protein 1 (anti-PD-1) therapy (nivolumab). She presented with a sarcomatoid carcinoma of the scalp with bone lysis as well as vascular and meningeal contact. Nivolumab was initiated because it has emerged as a promising immunotherapy. We observed a dramatic tumor response with excellent tolerance. However, while on nivolumab therapy she developed two large skin melanomas and several squamous cell carcinomas, which have been resected...
October 8, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28982910/febuxostat-as-a-prophylaxis-for-tumor-lysis-syndrome-in-children-with-hematological-malignancies
#2
Kenji Kishimoto, Ryoji Kobayashi, Daiki Hori, Hirozumi Sano, Daisuke Suzuki, Kunihiko Kobayashi
AIM: The aim of the present study was to determine if febuxostat could prevent tumor lysis syndrome (TLS) in children who received induction chemotherapy for hematologic malignancies. PATIENTS AND METHODS: A retrospective analysis was performed in 45 pediatric patients with hematological malignancies who received febuxostat (10 mg daily, n=20) or allopurinol (300 mg/m(2) daily, n=25) as a prophylaxis for TLS. RESULTS: A significant decrease of serum uric acid (UA) level was observed in patients with febuxostat over the first 2 days (6...
October 2017: Anticancer Research
https://www.readbyqxmd.com/read/28981915/trispecific-antibodies-for-cd16a-directed-nk-cell-engagement-and-dual-targeting-of-tumor-cells
#3
Thorsten Gantke, Michael Weichel, Carmen Herbrecht, Uwe Reusch, Kristina Ellwanger, Ivica Fucek, Markus Eser, Thomas Müller, Remko Griep, Vera Molkenthin, Eugene A Zhukovsky, Martin Treder
Bispecific antibodies that redirect the lytic activity of cytotoxic immune effector cells, such as T- and NK cells, onto tumor cells have emerged as a highly attractive and clinically validated treatment modality for hematological malignancies. Advancement of this therapeutic concept into solid tumor indications, however, is hampered by the scarcity of targetable antigens that are surface-expressed on tumor cells but demonstrate only limited expression on healthy tissues. To overcome this limitation, the concept of dual-targeting, i...
August 17, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/28977785/innate-immunity-protein-tag7-induces-3-distinct-populations-of-cytotoxic-cells-that-use-different-mechanisms-to-exhibit-their-antitumor-activity-on-human-leukocyte-antigen-deficient-cancer-cells
#4
Tatiana N Sharapova, Olga K Ivanova, Natalia V Soshnikova, Elena A Romanova, Lidia P Sashchenko, Denis V Yashin
The search for new immune response mechanisms capable of controlling immune-evasive tumor cells devoid of the MHC antigen is a challenging task for immunologists. In this study, we found that the treatment of human peripheral blood lymphocytes with the innate immunity protein Tag7 (PGRP-S, PGLYRP1) induces differentiation of the populations of NK (natural killer) cells and CD8+ and CD4+ T lymphocytes that are cytotoxic for human leukocyte antigen-negative tumor cells. These populations employ different mechanisms of tumor cell lysis (based on the release of granzymes in the case of NK cells and on the FasL-Fas interaction in the case of CD8+ and CD4+ T lymphocytes) and induce different death pathways (apoptosis or necroptosis) in tumor cells...
October 4, 2017: Journal of Innate Immunity
https://www.readbyqxmd.com/read/28972395/venetoclax-for-the-treatment-of-chronic-lymphocytic-leukemia
#5
Massimo Gentile, Annamaria Petrungaro, Giuseppina Uccello, Ernesto Vigna, Anna Grazia Recchia, Nadia Caruso, Sabrina Bossio, Laura De Stefano, Angela Palummo, Francesca Storino, Massimo Martino, Fortunato Morabito
Venetoclax, an orally bioavailable inhibitor of BCL-2, was approved in 2016 by the United States Food and Drug Administration (FDA) for the treatment of chronic lymphocytic leukemia (CLL) patients with 17p deletion [del(17p)], who have received at least one prior therapy. Areas covered: We focus on the mechanism of action of venetoclax and on the clinical trial data that led to the approval of venetoclax for CLL patients. We also review the studies in which this drug has being explored in combination with other anti-CLL drugs...
November 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28970228/expression-of-a-peptidoglycan-hydrolase-from-lytic-bacteriophages-atu_ph02-and-atu_ph03-triggers-lysis-of-agrobacterium-tumefaciens
#6
Hedieh Attai, Jeanette Rimbey, George P Smith, Pamela J B Brown
In order to provide food security, innovative approaches to preventing plant disease are currently being explored. Here, we demonstrate that lytic bacteriophages and phage lysis proteins are effective at triggering lysis of the phytopathogen Agrobacterium tumefaciens Phages Atu_ph02 and Atu_ph03 were isolated from wastewater and induce lysis of C58-derived strains of A. tumefaciens Co-inoculation of A. tumefaciens with phage onto potato discs limits tumor formation. The genomes of Atu_ph02 and Atu_ph03 are nearly identical and ∼42% identical to T7 supercluster phages...
September 29, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28968974/cap-dependent-translational-control-of-oncolytic-measles-virus-infection-in-malignant-mesothelioma
#7
Blake A Jacobson, Ahad A Sadiq, Shaogeng Tang, Joe Jay-Dixon, Manish R Patel, Jeremy Drees, Brent S Sorenson, Stephen J Russell, Robert A Kratzke
Malignant mesothelioma has a poor prognosis for which there remains an urgent need for successful treatment approaches. Infection with the Edmonston vaccine strain (MV-Edm) derivative of measles virus results in lysis of cancer cells and has been tested in clinical trials for numerous tumor types including mesothelioma. Many factors play a role in MV-Edm tumor cell selectivity and cytopathic activity while also sparing non-cancerous cells. The MV-Edm receptor CD46 (cluster of differentiation 46) was demonstrated to be significantly higher in mesothelioma cells than in control cells...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28960357/the-effect-of-therapeutic-leukapheresis-on-early-complications-and-outcomes-in-patients-with-acute-leukemia-and-hyperleukocytosis-a-propensity-score-matched-study
#8
Min Hyuk Choi, Yeon Hwa Choe, Yongjung Park, Hyunjin Nah, Sinyoung Kim, Seok Hoon Jeong, Hyun Ok Kim
BACKGROUND: Hyperleukocytosis in acute leukemia is associated with higher early mortality due to the major complications of leukostasis, tumor lysis syndrome (TLS), and disseminated intravascular coagulopathy (DIC). Leukapheresis remains an important modality for the management of patients with acute leukemia and hyperleukocytosis. However, the role of leukapheresis in early mortality is controversial. This study sought to evaluate the prognostic impact of leukapheresis and its beneficial effects on TLS and DIC...
September 28, 2017: Transfusion
https://www.readbyqxmd.com/read/28955655/oncolytic-viruses-natural-and-genetically-engineered-cancer-immunotherapies
#9
REVIEW
Sachin R Jhawar, Aditya Thandoni, Praveen K Bommareddy, Suemair Hassan, Frederick J Kohlhapp, Sharad Goyal, Jason M Schenkel, Ann W Silk, Andrew Zloza
There has long been interest in innovating an approach by which tumor cells can be selectively and specifically targeted and destroyed. The discovery of viruses that lyse tumor cells, termed oncolytic viruses (OVs), has led to a revolution in the treatment of cancer. The potential of OVs to improve the therapeutic ratio is derived from their ability to preferentially infect and replicate in cancer cells while avoiding destruction of normal cells surrounding the tumor. Two main mechanisms exist through which these viruses are reported to improve outcomes: direct lysis of tumor cells and indirect augmentation of host anti-tumor immunity...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28945711/venetoclax-management-and-care-for-patients-with-relapsed-or-refractory-chronic-lymphocytic-leukemia%C3%A2
#10
Heather Brumbaugh Paradis, Debbie Alter, Diane Llerandi
BACKGROUND: Venetoclax (Venclexta™) is a potent, selective, orally available, small-molecule B-cell lymphoma 2 inhibitor that achieves response rates of about 80% and has an acceptable safety profile for patients with relapsed or refractory chronic lymphocytic leukemia (CLL).
. OBJECTIVES: The aim was to describe treatment management considerations when caring for patients using venetoclax.
. METHODS: A review was done of safety and management considerations based on current clinical practice and 240 patients with CLL who received venetoclax monotherapy on clinical trials from 2011-2016...
October 1, 2017: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/28940544/chronic-granulomatous-dermatitis-induced-by-talimogene-laherparepvec-therapy-of-melanoma-metastases
#11
Ashlyn S Everett, Peter G Pavlidakey, Carlo M Contreras, Jennifer F De Los Santos, Ju Y Kim, Svetlana B McKee, Howard L Kaufman, Robert M Conry
Talimogene laherparepvec is the first oncolytic viral immunotherapy approved by the FDA, for advanced melanoma consisting of genetically modified herpes simplex type 1 virus which selectively replicates causing tumor lysis, expressing GM-CSF and activating dendritic cells. Intratumoral injection of TVEC produces objective response in 41% of stage IIB-IV M1a melanoma. However, clinical response assessments can be problematic due to immune-related inflammation at established tumor sites. Herein, we report 5 cases of granulomatous dermatitis developing at sites of TVEC injection associated with pathologic complete response in 4 of 5 patients...
September 22, 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/28939757/pd-1-blockade-promotes-epitope-spreading-in-anticancer-cd8-t-cell-responses-by-preventing-fratricidal-death-of-subdominant-clones-to-relieve-immunodomination
#12
Arash Memarnejadian, Courtney E Meilleur, Christopher R Shaler, Khashayarsha Khazaie, Jack R Bennink, Todd D Schell, S M Mansour Haeryfar
The interactions between programmed death-1 (PD-1) and its ligands hamper tumor-specific CD8(+) T cell (TCD8) responses, and PD-1-based "checkpoint inhibitors" have shown promise in certain cancers, thus revitalizing interest in immunotherapy. PD-1-targeted therapies reverse TCD8 exhaustion/anergy. However, whether they alter the epitope breadth of TCD8 responses remains unclear. This is an important question because subdominant TCD8 are more likely than immunodominant clones to escape tolerance mechanisms and may contribute to protective anticancer immunity...
September 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28929002/spontaneous-tumor-lysis-syndrome-in-a-patient-with-a-dedifferentiated-endometrial-adenocarcinoma
#13
Shinichi Harada, Keiki Nagaharu, Youichirou Baba, Tetsuya Murata, Toshiro Mizuno, Keiki Kawakami
Tumor lysis syndrome (TLS) is an oncological emergency caused by massive cytolysis of malignant cells. This syndrome eventually induces metabolic abnormalities. TLS is observed mainly among tumors with rapid cell proliferation or high sensitivity to antineoplastic treatment. In rare cases, TLS occurs without any cytotoxic treatment. Previous reports have shown that alternative stress including proceeding infection or an operation might play a role in TLS. However, exact mechanism of spontaneous TLS remains unknown...
2017: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/28919994/effect-of-entinostat-on-nk-cell-mediated-cytotoxicity-against-osteosarcoma-cells-and-osteosarcoma-lung-metastasis
#14
Simin Kiany, Gangxiong Huang, Eugenie S Kleinerman
There is a crucial need for a new therapeutic approach for osteosarcoma (OS) lung metastasis since this disease remains the main cause of mortality in OS. We previously demonstrated that natural killer (NK) cell therapy has minimal efficacy against OS metastasis. This study determined whether the histone deacetylase inhibitor entinostat could immunosensitize OS cells to NK cell lysis and increases the efficacy of NK cell therapy for OS lung metastasis. Entinostat upregulated ligands for NK cell-activating receptors (major histocompatibility complex [MHC] class I polypeptide-related chain A [MICA] and B [MICB]; UL16 binding proteins 1, 2, 5, and 6; and CD155) on OS cells both in vitro and in vivo and led to more susceptibility to NK cell-mediated cytotoxicity in vitro...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919885/trypanosoma-cruzi-evades-the-complement-system-as-an-efficient-strategy-to-survive-in-the-mammalian-host-the-specific-roles-of-host-parasite-molecules-and-trypanosoma-cruzi-calreticulin
#15
REVIEW
Galia Ramírez-Toloza, Arturo Ferreira
American Trypanosomiasis is an important neglected reemerging tropical parasitism, infecting about 8 million people worldwide. Its agent, Trypanosoma cruzi, exhibits multiple mechanisms to evade the host immune response and infect host cells. An important immune evasion strategy of T. cruzi infective stages is its capacity to inhibit the complement system activation on the parasite surface, avoiding opsonizing, immune stimulating and lytic effects. Epimastigotes, the non-infective form of the parasite, present in triatomine arthropod vectors, are highly susceptible to complement-mediated lysis while trypomastigotes, the infective form, present in host bloodstream, are resistant...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28904174/in-hospital-outcomes-of-tumor-lysis-syndrome-a-population-based-study-using-the-national-inpatient-sample
#16
Urshila Durani, Nilay D Shah, Ronald S Go
The epidemiology and outcomes of tumor lysis syndrome (TLS) are understudied. We used the National Inpatient Sample (NIS), a nationally representative weighted sample of all U.S. hospital discharges, to study outcomes and predictors of mortality in hospitalized patients with TLS. The NIS was queried for patients with a discharge diagnosis of TLS (ICD-9 code 277.88) from 2010-2013. Baseline characteristics and outcomes were analyzed. A multivariable logistic regression analysis was performed to identify predictors of mortality...
September 13, 2017: Oncologist
https://www.readbyqxmd.com/read/28893339/spontaneous-tumor-lysis-syndrome-in-a-patient-with-newly-diagnosed-metastatic-colonic-adenocarcinoma
#17
Ross Berringer
Acute tumor lysis syndrome in the absence of cytotoxic therapy is an uncommon event but has been reported with hematologic malignancies. The case described below illustrates spontaneous tumor lysis syndrome in the context of a rapidly proliferating metastatic colonic adenocarcinoma. Clinicians should consider ordering phosphate, uric acid, and calcium when assessing patients with recently diagnosed or suspected malignancy.
September 12, 2017: CJEM
https://www.readbyqxmd.com/read/28892414/efficacy-of-recombinant-adenovirus-expressing-a-fusion-gene-from-gm-csf-and-epstein-barr-virus-lmp2a-in-a-mouse-tumor-model
#18
Qingjie Xue, Xiuzheng Li, Chunqing Yang, Bingyuan Ji, Yunqing Li, Yingchun Yan, Xinxin Yang, Chunmei Wang, Ting Chen
In this study, purified GM-CSF and LMP2A mRNAs were amplified by PCR. Then, the GM-CSF and LMP2A sequences were connected by the polypeptide linker (Gly4Ser)3 using gene splicing by overlap extension. The constructed fusion gene GC2A was inserted into the adenovirus vector. Then the recombinant vector was introduced into HEK 293T cells by calcium phosphate transfection to package the adenovirus. The levels of antibodies against the GM-CSF and LMP2Afusion proteins were measured by ELISA, and the CTL activity of the mouse splenic lymphocytes was determined by lactate dehydrogenase (LDH) release assay...
September 11, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28891704/mucoepidermoid-carcinoma-in-the-skull-of-an-orange-winged-amazon-parrot-amazona-amazonica
#19
Melissa R Nau, James W Carpenter, Denise Lin, Sanjeev Narayanan, Mackenzie Hallman
A 33-year-old female intact orange-winged Amazon parrot (Amazona amazonica) presented for a slowly growing mass over the right eye. A computed tomography scan performed with and without intravenous contrast revealed a heterogeneous mixed soft tissue and mineral-dense mass with a small area of non-contrast-enhancing fluid density located between the orbits at the caudal aspect of the nasal passages, with associated lysis of the right caudal nasal passage and the right frontal bone. Following euthanasia, the mass was found to consist of soft tissue between the right eye and nostril over the right frontal bone...
September 2017: Journal of Avian Medicine and Surgery
https://www.readbyqxmd.com/read/28887473/complete-sequence-based-pathway-analysis-by-differential-on-chip-dna-and-rna-extraction-from-a-single-cell
#20
D van Strijp, R C M Vulders, N A Larsen, J Schira, L Baerlocher, M A van Driel, M Pødenphant, T S Hansen, A Kristensen, K U Mir, T Olesen, W F J Verhaegh, R Marie, P J van der Zaag
We demonstrate on-chip, differential DNA and RNA extraction from a single cell using a microfluidic chip and a two-stage lysis protocol. This method enables direct use of the whole extract, without additional washing steps, reducing sample loss. Using this method, the tumor driving pathway in individual cells from a colorectal cancer cell line was determined by applying a Bayesian computational pathway model to sequences obtained from the RNA fraction of a single cell and, the mutations driving the pathway were determined by analyzing sequences obtained from the DNA fraction of the same single cell...
September 8, 2017: Scientific Reports
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