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https://www.readbyqxmd.com/read/28346673/clinical-features-of-bim-deletion-polymorphism-and-its-relation-with-crizotinib-primary-resistance-in-chinese-patients-with-alk-ros1-fusion-positive-non-small-cell-lung-cancer
#1
Limin Zhang, Tao Jiang, Xuefei Li, Yan Wang, Chao Zhao, Sha Zhao, Lei Xi, Shijia Zhang, Xiaozhen Liu, Yijun Jia, Hui Yang, Jinpeng Shi, Chunxia Su, Shengxiang Ren, Caicun Zhou
BACKGROUND: The authors' previous study demonstrated that the B-cell chronic lymphocytic leukemia/lymphoma (Bcl-2)-like 11 (BCL2L11) (Bim) deletion polymorphism was associated with poor clinical response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in patients with non-small cell lung cancer (NSCLC) with EGFR mutations. The objective of the current study was to investigate the impact of the Bim deletion polymorphism among patients with anaplastic lymphoma kinase (ALK)-positive or ROS proto-oncogene 1, receptor tyrosine kinase (ROS1)-positive NSCLC who were treated with crizotinib...
March 27, 2017: Cancer
https://www.readbyqxmd.com/read/28346517/cd22-is-required-for-formation-of-memory-b-cell-precursors-within-germinal-centers
#2
Craig P Chappell, Kevin E Draves, Edward A Clark
CD22 is a BCR co-receptor that regulates B cell signaling, proliferation and survival and is required for T cell-independent Ab responses. To investigate the role of CD22 during T cell-dependent (TD) Ab responses and memory B cell formation, we analyzed Ag-specific B cell responses generated by wild-type (WT) or CD22-/- B cells following immunization with a TD Ag. CD22-/- B cells mounted normal early Ab responses yet failed to generate either memory B cells or long-lived plasma cells, whereas WT B cells formed both populations...
2017: PloS One
https://www.readbyqxmd.com/read/28346506/specific-expression-of-novel-long-non-coding-rnas-in-high-hyperdiploid-childhood-acute-lymphoblastic-leukemia
#3
Mathieu Lajoie, Simon Drouin, Maxime Caron, Pascal St-Onge, Manon Ouimet, Romain Gioia, Marie-Hélène Lafond, Ramon Vidal, Chantal Richer, Karim Oualkacha, Arnaud Droit, Daniel Sinnett
Pre-B cell childhood acute lymphoblastic leukemia (pre-B cALL) is a heterogeneous disease involving many subtypes typically stratified using a combination of cytogenetic and molecular-based assays. These methods, although widely used, rely on the presence of known chromosomal translocations, which is a limiting factor. There is therefore a need for robust, sensitive, and specific molecular biomarkers unaffected by such limitations that would allow better risk stratification and consequently better clinical outcome...
2017: PloS One
https://www.readbyqxmd.com/read/28346408/gut-microbial-metabolites-limit-the-frequency-of-autoimmune-t-cells-and-protect-against-type-1-diabetes
#4
Eliana Mariño, James L Richards, Keiran H McLeod, Dragana Stanley, Yu Anne Yap, Jacinta Knight, Craig McKenzie, Jan Kranich, Ana Carolina Oliveira, Fernando J Rossello, Balasubramanian Krishnamurthy, Christian M Nefzger, Laurence Macia, Alison Thorburn, Alan G Baxter, Grant Morahan, Lee H Wong, Jose M Polo, Robert J Moore, Trevor J Lockett, Julie M Clarke, David L Topping, Leonard C Harrison, Charles R Mackay
Gut dysbiosis might underlie the pathogenesis of type 1 diabetes. In mice of the non-obese diabetic (NOD) strain, we found that key features of disease correlated inversely with blood and fecal concentrations of the microbial metabolites acetate and butyrate. We therefore fed NOD mice specialized diets designed to release large amounts of acetate or butyrate after bacterial fermentation in the colon. Each diet provided a high degree of protection from diabetes, even when administered after breakdown of immunotolerance...
March 27, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28346398/sirtuin-1-sirt1-overexpression-in-baf3-cells-contributes-to-cell-proliferation-promotion-apoptosis-resistance-and-pro-inflammatory-cytokine-production
#5
Qian Wang, Chao Yan, Miaomiao Xin, Li Han, Yunqing Zhang, Mingshu Sun
BACKGROUND B lymphocyte hyperactivity is a main characteristic of systemic lupus erythematosus (SLE), and B lymphocytes play a prominent pathogenic role in the development and progression of SLE. The aim of this study was to investigate the role of Sirtuin 1 (Sirt1) in B lymphocytes. MATERIAL AND METHODS Mouse B lymphocytes BaF3 was transfected with Sirt1 vector or shRNA against Sirt1. Then the transfected cells viability and apoptosis were respectively determined by MTT assay and flow cytometry. In addition, the mRNA levels of three pro-inflammatory cytokines and p53 were detected by RT-PCR...
March 27, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28346397/the-process-and-regulatory-components-of-inflammation-in-brain-oncogenesis
#6
REVIEW
A G M Mostofa, Surendra R Punganuru, Hanumantha Rao Madala, Mohammad Al-Obaide, Kalkunte S Srivenugopal
Central nervous system tumors comprising the primary cancers and brain metastases remain the most lethal neoplasms and challenging to treat. Substantial evidence points to a paramount role for inflammation in the pathology leading to gliomagenesis, malignant progression and tumor aggressiveness in the central nervous system (CNS) microenvironment. This review summarizes the salient contributions of oxidative stress, interleukins, tumor necrosis factor-α (TNF-α), cyclooxygenases, and transcription factors such as signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and the associated cross-talks to the inflammatory signaling in CNS cancers...
March 27, 2017: Biomolecules
https://www.readbyqxmd.com/read/28346226/a-tlr9-dependent-checkpoint-governs-b-cell-responses-to-dna-containing-antigens
#7
Vishal J Sindhava, Michael A Oropallo, Krishna Moody, Martin Naradikian, Lauren E Higdon, Lin Zhou, Arpita Myles, Nathaniel Green, Kerstin Nündel, William Stohl, Amanda M Schmidt, Wei Cao, Stephanie Dorta-Estremera, Taku Kambayashi, Ann Marshak-Rothstein, Michael P Cancro
Mature B cell pools retain a substantial proportion of polyreactive and self-reactive clonotypes, suggesting that activation checkpoints exist to reduce the initiation of autoreactive B cell responses. Here, we have described a relationship among the B cell receptor (BCR), TLR9, and cytokine signals that regulate B cell responses to DNA-containing antigens. In both mouse and human B cells, BCR ligands that deliver a TLR9 agonist induce an initial proliferative burst that is followed by apoptotic death. The latter mechanism involves p38-dependent G1 cell-cycle arrest and subsequent intrinsic mitochondrial apoptosis and is shared by all preimmune murine B cell subsets and CD27- human B cells...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28345816/germline-variation-in-the-3-untranslated-region-of-the-pou2af1-gene-is-associated-with-susceptibility-to-lymphoma
#8
Kan Zhai, Jiang Chang, Jinlong Hu, Chen Wu, Dongxin Lin
Genetic variations in certain genes may alter the susceptibility to lymphoma. We searched electronic databases and selected candidate single-nucleotide polymorphisms (SNPs) located within 3'-untranslated regions (3'-UTRs) that might affect miRNA-binding ability in the 50 most dysregulated genes in lymphoma for further study. We found that rs1042752-located in the 3'-UTR of POU2AF1, which plays a vital role in lymphomagenesis-was significantly associated with lymphoma risk in a case-control study with 793 patients and 939 controls...
March 27, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28345522/regulatory-b-cells-and-allergy-uncovering-the-link
#9
I Mota, C Martins, L M Borrego
No abstract text is available yet for this article.
March 27, 2017: Journal of Investigational Allergology & Clinical Immunology
https://www.readbyqxmd.com/read/28345492/rasburicase-induced-methemoglobinemia-the-eyes-do-not-see-what-the-mind-does-not-know
#10
Uroosa Ibrahim, Amina Saqib, Farhan Mohammad, Jean Paul Atallah, Marcel Odaimi
Rasburicase is indicated for the prevention and treatment of tumor lysis syndrome which can be a potentially life-threatening emergency. The drug has oxidizing potential and as an adverse effect, it can convert the ferrous form of iron in erythrocytes to its ferric form resulting in the formation of methemoglobin which makes the heme component incapable of carrying oxygen. Patients with glucose-6-phosphate dehydrogenase enzyme deficiency are at high risk of methemoglobinemia from oxidizing agents. Symptoms of methemoglobinemia range from none to life-threatening hypoxemia, cyanosis and respiratory compromise...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28345327/frequency-of-epstein-barr-virus-type-1-among-nasopharyngeal-carcinomas-in-iranian-patients
#11
Toran Shahani, Manoochehr Makvandi, Alireza Samarbafzadeh, Ali Teimoori, Nastran Ranjbar, Nader saki, Soheila Nikakhlagh, Niloofar Neisi, Zeinab Hosseini, Samira Pourrezaei, Abdolnabi Shabani, Hashem Radmehr, Hamide Mehravaran, Hadis Kiani, Azadeh Haghi
Background: Around 95% of the world’s population are infected with the Epstein-Barr virus (EBV), which can persist latent in B lymphocytes and epithelial cells life-long. EBV has been linked with lymphoid and epithelial cancers and persistence of EBV infection in lymphoid or epithelial cells may result in virus-associated B-cell tumors or nasopharyngeal carcinomas (NPC). This study was conducted to determine the frequency of EBV DNA in nasopharyngeal carcinoma tissue of Iranian patients. Materials and methods: A total of 50 blocks of formalin-fixed paraffin-embedded tissue of NPCs from 38 (76 %) male and 12 (24%) female patients were collected from archives of Ahvaz hospitals...
February 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28345004/homology-directed-recombination-for-enhanced-engineering-of-chimeric-antigen-receptor-t-cells
#12
Malika Hale, Baeckseung Lee, Yuchi Honaker, Wai-Hang Leung, Alexandra E Grier, Holly M Jacobs, Karen Sommer, Jaya Sahni, Shaun W Jackson, Andrew M Scharenberg, Alexander Astrakhan, David J Rawlings
Gene editing by homology-directed recombination (HDR) can be used to couple delivery of a therapeutic gene cassette with targeted genomic modifications to generate engineered human T cells with clinically useful profiles. Here, we explore the functionality of therapeutic cassettes delivered by these means and test the flexibility of this approach to clinically relevant alleles. Because CCR5-negative T cells are resistant to HIV-1 infection, CCR5-negative anti-CD19 chimeric antigen receptor (CAR) T cells could be used to treat patients with HIV-associated B cell malignancies...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28345001/effective-depletion-of-pre-existing-anti-aav-antibodies-requires-broad-immune-targeting
#13
Victoria M Velazquez, Aaron S Meadows, Ricardo J Pineda, Marybeth Camboni, Douglas M McCarty, Haiyan Fu
Pre-existing antibodies (Abs) to AAV pose a critical challenge for the translation of gene therapies. No effective approach is available to overcome pre-existing Abs. Given the complexity of Ab production, overcoming pre-existing Abs will require broad immune targeting. We generated a mouse model of pre-existing AAV9 Abs to test multiple immunosuppressants, including bortezomib, rapamycin, and prednisolone, individually or in combination. We identified an effective approach combining rapamycin and prednisolone, reducing serum AAV9 Abs by 70%-80% at 4 weeks and 85%-93% at 8 weeks of treatment...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344995/global-manufacturing-of-car-t-cell-therapy
#14
REVIEW
Bruce L Levine, James Miskin, Keith Wonnacott, Christopher Keir
Immunotherapy using chimeric antigen receptor-modified T cells has demonstrated high response rates in patients with B cell malignancies, and chimeric antigen receptor T cell therapy is now being investigated in several hematologic and solid tumor types. Chimeric antigen receptor T cells are generated by removing T cells from a patient's blood and engineering the cells to express the chimeric antigen receptor, which reprograms the T cells to target tumor cells. As chimeric antigen receptor T cell therapy moves into later-phase clinical trials and becomes an option for more patients, compliance of the chimeric antigen receptor T cell manufacturing process with global regulatory requirements becomes a topic for extensive discussion...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344987/safe-and-effective-gene-therapy-for-murine-wiskott-aldrich-syndrome-using-an-insulated-lentiviral-vector
#15
Swati Singh, Iram Khan, Socheath Khim, Brenda Seymour, Karen Sommer, Matthew Wielgosz, Zachary Norgaard, Hans-Peter Kiem, Jennifer Adair, Denny Liggitt, Arthur Nienhuis, David J Rawlings
Wiskott-Aldrich syndrome (WAS) is a life-threatening immunodeficiency caused by mutations within the WAS gene. Viral gene therapy to restore WAS protein (WASp) expression in hematopoietic cells of patients with WAS has the potential to improve outcomes relative to the current standard of care, allogeneic bone marrow transplantation. However, the development of viral vectors that are both safe and effective has been problematic. While use of viral transcriptional promoters may increase the risk of insertional mutagenesis, cellular promoters may not achieve WASp expression levels necessary for optimal therapeutic effect...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344876/2b4-sap-signaling-is-required-for-the-priming-of-naive-cd8-t-cells-by-antigen-expressing-b-cells-and-b-lymphoma-cells
#16
Yu-Hsuan Huang, Kevin Tsai, Sara Y Tan, Sohyeong Kang, Mandy L Ford, Kenneth W Harder, John J Priatel
Mutations in SH2D1A gene that encodes SAP (SLAM-associated protein) result in X-linked lymphoproliferative disease (XLP), a rare primary immunodeficiency disease defined by exquisite sensitivity to the B-lymphotropic Epstein-Barr virus (EBV) and B cell lymphomas. However, the precise mechanism of how the loss of SAP function contributes to extreme vulnerability to EBV and the development of B cell lymphomas remains unclear. Here, we investigate the hypothesis that SAP is critical for CD8(+) T cell immune surveillance of antigen (Ag)-expressing B cells or B lymphoma cells under conditions of defined T cell receptor (TCR) signaling...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344873/a-specific-immune-and-lymphatic-profile-characterizes-the-pre-metastatic-state-of-the-sentinel-lymph-node-in-patients-with-early-cervical-cancer
#17
Cédric Balsat, Silvia Blacher, Michael Herfs, Maureen Van de Velde, Nicolas Signolle, Philippe Sauthier, Charles Pottier, Stéphanie Gofflot, Marjolein De Cuypere, Philippe Delvenne, Frédéric Goffin, Agnès Noel, Frédéric Kridelka
The lymph node (LN) pre-metastatic niche is faintly characterized in lymphophilic human neoplasia, although LN metastasis is considered as the strongest prognostic marker of patient survival. Due to its specific dissemination through a complex bilateral pelvic lymphatic system, early cervical cancer is a relevant candidate for investigating the early nodal metastatic process. In the present study, we analyzed in-depth both the lymphatic vasculature and the immune climate of pre-metastatic sentinel LN (SLN), in 48 cases of FIGO stage IB1 cervical neoplasms...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344861/zoledronic-acid-boosts-%C3%AE-%C3%AE-t-cell-activity-in-children-receiving-%C3%AE-%C3%AE-t-and-cd19-cell-depleted-grafts-from-an-hla-haplo-identical-donor
#18
A Bertaina, A Zorzoli, A Petretto, G Barbarito, E Inglese, P Merli, C Lavarello, L P Brescia, B De Angelis, G Tripodi, L Moretta, F Locatelli, I Airoldi
We demonstrated that γδ T cells of patients given HLA-haploidentical HSCT after removal of αβ(+) T cells and CD19(+) B cells are endowed with the capacity of killing leukemia cells after ex vivo treatment with zoledronic acid (ZOL). Thus, we tested the hypothesis that infusion of ZOL in patients receiving this type of graft may enhance γδ T-cell cytotoxic activity against leukemia cells. ZOL was infused every 28 d in 43 patients; most were treated at least twice. γδ T cells before and after ZOL treatments were studied in 33 of these 43 patients, till at least 7 mo after HSCT by high-resolution mass spectrometry, flow-cytometry, and degranulation assay...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344808/safety-tumor-trafficking-and-immunogenicity-of-chimeric-antigen-receptor-car-t-cells-specific-for-tag-72-in-colorectal-cancer
#19
Kristen M Hege, Emily K Bergsland, George A Fisher, John J Nemunaitis, Robert S Warren, James G McArthur, Andy A Lin, Jeffrey Schlom, Carl H June, Stephen A Sherwin
BACKGROUND: T cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. Here we report results of the first human trials of CAR-T cells in the treatment of solid tumors performed in the 1990s. METHODS: Patients with metastatic colorectal cancer (CRC) were treated in two phase 1 trials with first-generation retroviral transduced CAR-T cells targeting tumor-associated glycoprotein (TAG)-72 and including a CD3-zeta intracellular signaling domain (CART72 cells)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28344775/tertiary-lymphoid-organs-in-systemic-autoimmune-diseases-%C3%A2-pathogenic-or-protective
#20
REVIEW
William D Shipman, Dragos C Dasoveanu, Theresa T Lu
Tertiary lymphoid organs are found at sites of chronic inflammation in autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. These organized accumulations of T and B cells resemble secondary lymphoid organs and generate autoreactive effector cells. However, whether they contribute to disease pathogenesis or have protective functions is unclear. Here, we discuss how tertiary lymphoid organs can generate potentially pathogenic cells but may also limit the extent of the response and damage in autoimmune disease...
2017: F1000Research
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