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https://www.readbyqxmd.com/read/28532760/research-techniques-made-simple-high-throughput-sequencing-of-the-t-cell-receptor
#1
Tiago R Matos, Menno A de Rie, Marcel B M Teunissen
High-throughput sequencing (HTS) of the T-cell receptor (TCR) is a rapidly advancing technique that allows sensitive and accurate identification and quantification of every distinct T-cell clone present within any biological sample. The relative frequency of each individual clone within the full T-cell repertoire can also be studied. HTS is essential to expand our knowledge on the diversity of the TCR repertoire in homeostasis or under pathologic conditions, as well as to understand the kinetics of antigen-specific T-cell responses that lead to protective immunity (i...
June 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28529902/current-state-of-immunotherapy-for-non-small-cell-lung-cancer
#2
REVIEW
Jyoti Malhotra, Salma K Jabbour, Joseph Aisner
Lung cancer is the leading cause of cancer mortality and non-small cell lung cancer (NSCLC) accounts for more than 85% of all lung cancers. Platinum-based doublet chemotherapy is the standard first-line treatment for metastatic NSCLC when genomic testing reveals no targetable alteration such as epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) or ROS1 translocation/re-arrangements. But, chemotherapy produces response rates ranging only between 15-30%. For patients whose disease progresses on first-line chemotherapy, second-line therapy historically consists of taxane-based salvage chemotherapy with a response rate of less than 25%...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28526811/proteomic-analysis-of-cerebrospinal-fluid-from-children-with-central-nervous-system-tumors-identifies-candidate-proteins-relating-to-tumor-metastatic-spread
#3
Filippo Spreafico, Italia Bongarzone, Sara Pizzamiglio, Ruben Magni, Elena Taverna, Maida De Bortoli, Chiara M Ciniselli, Elena Barzanò, Veronica Biassoni, Alessandra Luchini, Lance A Liotta, Weidong Zhou, Michele Signore, Paolo Verderio, Maura Massimino
Central nervous system (CNS) tumors are the most common solid tumors in childhood. Since the sensitivity of combined cerebrospinal fluid (CSF) cytology and radiological neuroimaging in detecting meningeal metastases remains relatively low, we sought to characterize the CSF proteome of patients with CSF tumors to identify biomarkers predictive of metastatic spread. CSF samples from 27 children with brain tumors and 13 controls (extra-CNS non-Hodgkin lymphoma) were processed using core-shell hydrogel nanoparticles, and analyzed with reverse-phase liquid chromatography/electrospray tandem mass spectrometry (LC-MS/MS)...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525305/clinical-impact-of-the-cell-of-origin-classification-and-the-myc-bcl2-dual-expresser-status-in-diffuse-large-b-cell-lymphoma-treated-within-prospective-clinical-trials-of-the-german-high-grade-non-hodgkin-s-lymphoma-study-group
#4
Annette M Staiger, Marita Ziepert, Heike Horn, David W Scott, Thomas F E Barth, Heinz-Wolfram Bernd, Alfred C Feller, Wolfram Klapper, Monika Szczepanowski, Michael Hummel, Harald Stein, Dido Lenze, Martin-Leo Hansmann, Sylvia Hartmann, Peter Möller, Sergio Cogliatti, Georg Lenz, Lorenz Trümper, Markus Löffler, Norbert Schmitz, Michael Pfreundschuh, Andreas Rosenwald, German Ott
Purpose To explore the prognostic impact and interdependence of the cell-of-origin (COO) classification, dual expression (DE) of MYC and BCL2 proteins, and MYC, BCL2, and BCL6 translocations in two prospectively randomized clinical trials of patients with diffuse large B-cell lymphoma (DLBCL). Patients and Methods Overall, 452 formalin-fixed paraffin-embedded samples from two prospective, randomized DLBCL trials (RICOVER-60, prospective, randomized study for patients > 60 years, all IPI groups; and R-MegaCHOEP, prospective, randomized study for patients ≤ 60 years with age-adjusted IPI 2,3) of the German High-Grade Non-Hodgkin Lymphoma Study Group were analyzed with the Lymph2Cx assay for COO classification, with immunohistochemistry for MYC and BCL2, and with fluorescent in situ hybridization for MYC, BCL2, and BCL6 rearrangements...
May 19, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28522442/bcl2-expression-in-dlbcl-reappraisal-of-immunohistochemistry-with-new-criteria-for-therapeutic-biomarker-evaluation
#5
Naoko Tsuyama, Seiji Sakata, Satoko Baba, Yuko Mishima, Noriko Nishimura, Kyoko Ueda, Masahiro Yokoyama, Yasuhito Terui, Kiyohiko Hatake, Masanobu Kitagawa, Naoki Ishizuka, Naoto Tomita, Kengo Takeuchi
Overexpression of the BCL2 is associated with a poor prognosis in diffuse large B-cell lymphoma (DLBCL). The assessment of MYC immunohistochemistry (IHC) is becoming optimized, whereas the criteria for BCL2 positivity are highly variable. Furthermore, data on the frequency and prognostic value of BCL2 positivity are conflicting. We aimed to evaluate BCL2 expression by IHC and assess the prognostic significance of the histopathologically-scored BCL2 expression in 456 patients with DLBCL uniformly treated with standard immunochemotherapy (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone; R-CHOP)...
May 18, 2017: Blood
https://www.readbyqxmd.com/read/28521029/soluble-taci-and-soluble-bcma-as-biomarkers-in-primary-central-nervous-system-lymphoma
#6
Franziska S Thaler, Sarah A Laurent, Marion Huber, Matthias Mulazzani, Martin Dreyling, Uwe Ködel, Tania Kümpfel, Andreas Straube, Edgar Meinl, Louisa von Baumgarten
Background: B-cell survival is regulated through interactions of B-cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) with their receptors transmembrane activator and CAML interactor (TACI) and B-cell maturation antigen (BCMA). We evaluated the diagnostic potential of soluble TACI (sTACI) and soluble BCMA (sBCMA) in cerebrospinal fluid (CSF) and serum as biomarkers in primary CNS lymphoma (PCNSL). Methods: CSF (n=176) and serum samples (n=105) from patients with clinically or radiologically suspected PCNSL as well as from control patients were collected prospectively...
May 17, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28514730/circulating-micrornas-as-novel-biomarkers-of-alk-positive-nonsmall-cell-lung-cancer-and-predictors-of-response-to-crizotinib-therapy
#7
Liang-Liang Li, Li-Li Qu, Han-Jiang Fu, Xiao-Fei Zheng, Chuan-Hao Tang, Xiao-Yan Li, Jian Chen, Wei-Xia Wang, Shao-Xing Yang, Lin Wang, Guan-Hua Zhao, Pan-Pan Lv, Min Zhang, Yang-Yang Lei, Hai-Feng Qin, Hong Wang, Hong-Jun Gao, Xiao-Qing Liu
Circulating microRNAs are potential diagnostic and predictive biomarkers, but have not been investigated for patients with anaplastic lymphoma kinase (ALK)-positive lung cancer. In this exploratory study, we sought to identify potential plasma biomarkers for ALK-positive non-small cell lung cancer (NSCLC). A microRNA microarray was used to select ALK-related microRNAs in ALK-positive NSCLC (n = 3), ALK-negative NSCLC (n = 3), and healthy subjects (n = 3). Plasma levels of 21 microRNAs were differentially expressed for ALK-positive and ALK-negative NSCLC, including 14 down-regulated and 7 up-regulated microRNAs...
April 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28510589/establishment-of-a-combination-scoring-method-for-diagnosis-of-ocular-adnexal-lymphoproliferative-disease
#8
Xiao-Li Qu, Yan Hei, Li Kang, Xin-Ji Yang, Yi Wang, Xiao-Zhong Lu, Li-Hua Xiao, Guang Yang
Lymphoproliferative diseases (LPDs) of the ocular adnexa encompass the majority of orbital diseases and include reactive follicular hyperplasia (RFH), atypical lymphoid hyperplasia (ALH), and mucosa-associated lymphoid tissue lymphoma (MALToma). Lymphoid follicles (LFs) are usually observed during the histological examination of LPDs. Currently, because there is a lack of specific clinical signs and diagnostic immunohistochemical biomarkers, it is difficult for pathologists to distinguish MALToma from ocular RFH and ALH, which makes the clinical management of these conditions difficult...
2017: PloS One
https://www.readbyqxmd.com/read/28507793/composite-biomarkers-defined-by-multiparametric-immunofluorescence-analysis-identify-alk-positive-adenocarcinoma-as-a-potential-target-for-immunotherapy
#9
Hélène Roussel, Eléonore De Guillebon, Lucie Biard, Marion Mandavit, Laure Gibault, Elisabeth Fabre, Martine Antoine, Paul Hofman, Michèle Beau-Faller, Hélène Blons, Claire Danel, Françoise Le Pimpec Barthes, Alain Gey, Clémence Granier, Marie Wislez, Pierre Laurent-Puig, Stéphane Oudard, Patrick Bruneval, Cécile Badoual, Jacques Cadranel, Eric Tartour
Anaplastic lymphoma kinase (ALK) inhibitors have been successfully developed for non-small cell lung carcinoma (NSCLC) displaying chromosomal rearrangements of the ALK gene, but unfortunately resistance invariably occurs. Blockade of the PD-1-PD-L1/2 inhibitory pathway constitutes a breakthrough for the treatment of NSCLC. Some predictive biomarkers of clinical response to this therapy are starting to emerge, such as PD-L1 expression by tumor/stromal cells and infiltration by CD8(+) T cells expressing PD-1...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507202/determination-of-volatile-organic-compounds-exhaled-by-cell-lines-derived-from-hematological-malignancies
#10
Hongxia Tang, Yan Lu, Lulu Zhang, Zhonghui Wu, Xiaofang Hou, Hailong Xia
Background: The gas human exhaled contains many volatile organic compounds (VOCs), which is related to the health status of body. Analysis of VOCs has been proposed as a noninvasive diagnostic tool for certain cancers. Detailed research on the VOCs in gas exhaled by cell can characterize cell type specific metabolites and may be helpful to detect the cancer markers in clinical practice. Methods: Solid phase microextraction-gas chromatography-mass spectrometry was used to detect VOCs in the headspace of tissue culture flask in non-Hodgkin's lymphoma cell line JEKO and acute mononuclear leukemia cell line SHI-1, to elaborate the characteristic gaseous biomarkers of hematological malignancies...
May 15, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28505169/molecular-basis-of-targeted-therapy-in-t-nk-cell-lymphoma-leukemia-a-comprehensive-genomic-and-immunohistochemical-analysis-of-a-panel-of-33-cell-lines
#11
Rufino Mondejar, Cristina Pérez, Arantza Onaindia, Nerea Martinez, Julia González-Rincón, Helena Pisonero, Jose Pedro Vaqué, Laura Cereceda, Miguel Santibañez, Margarita Sánchez-Beato, Miguel Angel Piris
T and NK-cell lymphoma is a collection of aggressive disorders with unfavorable outcome, in which targeted treatments are still at a preliminary phase. To gain deeper insights into the deregulated mechanisms promoting this disease, we searched a panel of 31 representative T-cell and 2 NK-cell lymphoma/leukemia cell lines for predictive markers of response to targeted therapy. To this end, targeted sequencing was performed alongside the expression of specific biomarkers corresponding to potentially activated survival pathways...
2017: PloS One
https://www.readbyqxmd.com/read/28504647/identification-of-a-nucleoside-analog-active-against-adenosine-kinase-expressing-plasma-cell-malignancies
#12
Utthara Nayar, Jouliana Sadek, Jonathan Reichel, Denise Hernandez-Hopkins, Gunkut Akar, Peter J Barelli, Michelle A Sahai, Hufeng Zhou, Jennifer Totonchy, David Jayabalan, Ruben Niesvizky, Ilaria Guasparri, Duane Hassane, Yifang Liu, Shizuko Sei, Robert H Shoemaker, J David Warren, Olivier Elemento, Kenneth M Kaye, Ethel Cesarman
Primary effusion lymphoma (PEL) is a largely incurable malignancy of B cell origin with plasmacytic differentiation. Here, we report the identification of a highly effective inhibitor of PEL. This compound, 6-ethylthioinosine (6-ETI), is a nucleoside analog with toxicity to PEL in vitro and in vivo, but not to other lymphoma cell lines tested. We developed and performed resistome analysis, an unbiased approach based on RNA sequencing of resistant subclones, to discover the molecular mechanisms of sensitivity...
May 15, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28499278/long-non-coding-rnas-in-b-cell-malignancies-a-comprehensive-overview
#13
REVIEW
Lucia Nobili, Domenica Ronchetti, Elisa Taiana, Antonino Neri
B-cell malignancies constitute a large part of hematological neoplasias. They represent a heterogeneous group of diseases, including Hodgkin's lymphoma, most non-Hodgkin's lymphomas (NHL), some leukemias and myelomas. B-cell malignancies reflect defined stages of normal B-cell differentiation and this represents the major basis for their classification. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts longer than 200 nucleotides, for which many recent studies have demonstrated a function in regulating gene expression, cell biology and carcinogenesis...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28497093/association-between-abnormal-serum-free-light-chains-ratio-and-known-prognostic-factors-in-lymphoma-a-nephrology-viewpoint
#14
Minoosh Moghimi, Mahshid Kashkooli Behroozi, Mehdi Maghbooli, Sattar Jafari, Saeideh Mazloomzadeh, Aiyoub Pezeshgi
Introduction: The serum immunoglobulin free light chain (FLC) assay quantities of free kappa (κ) and lambda (λ) light chains. This assay has prognostic value in plasma cell proliferative disorders. There are limited data on serum FLC in B-cell malignancies. Objectives: The aim of this study was to compare the known prognostic factors in non-Hodgkin's lymphoma of the type B-cell and Hodgkin disease with an abnormal secretion amount of light chains in these lymphomas. Patients and Methods: The association of pretreatment FLC and FLC ratio (κ:λ) with previously known prognostic factors for lymphoma such as the international prognostic index (IPI) and B symptoms were evaluated in 50 patients with Hodgkin's and non-Hodgkin's lymphoma...
2017: Journal of Renal Injury Prevention
https://www.readbyqxmd.com/read/28487884/diffuse-large-b-cell-lymphoma-can-genomics-improve-treatment-options-for-a-curable-cancer
#15
REVIEW
Amit Dipak Amin, Tara L Peters, Lingxiao Li, Soumya Sundara Rajan, Ramesh Choudhari, Soham D Puvvada, Jonathan H Schatz
Gene-expression profiling and next-generation sequencing have defined diffuse large B-cell lymphoma (DLBCL), the most common lymphoma diagnosis, as a heterogeneous group of subentities. Despite ongoing explosions of data illuminating disparate pathogenic mechanisms, however, the five-drug chemoimmunotherapy combination R-CHOP remains the frontline standard treatment. This has not changed in 15 years, since the anti-CD20 monoclonal antibody rituximab was added to the CHOP backbone, which first entered use in the 1970s...
May 2017: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/28482851/checkpoint-inhibitors-in-hematological-malignancies
#16
REVIEW
Chi Young Ok, Ken H Young
Inhibitory molecules such as PD-1, CTLA-4, LAG-3, or TIM-3 play a role to keep a balance in immune function. However, many cancers exploit such molecules to escape immune surveillance. Accumulating data support that their functions are dysregulated in lymphoid neoplasms, including plasma cell myeloma, myelodysplastic syndrome, and acute myeloid leukemia. In lymphoid neoplasms, aberrations in 9p24.1 (PD-L1, PD-L2, and JAK2 locus), latent Epstein-Barr virus infection, PD-L1 3'-untranslated region disruption, and constitutive JAK-STAT pathway are known mechanisms to induce PD-L1 expression in lymphoma cells...
May 8, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28480776/advances-in-the-role-of-cytogenetic-analysis-in-the-molecular-diagnosis-of-b-cell-lymphomas
#17
Béatrice Grange, Evelyne Callet-Bauchu, Gilles Salles, Pierre Sujobert
Cytogenetic abnormalities represent essential determinants of diagnosis and prognosis in B-cell lymphomas. Their theranostic value is increasingly significant with the development of targeted therapies, in order to adapt the treatment at diagnosis as well as when relapse occurs. Areas covered: As the significance of these biomarkers is influenced by the technology used to detect them, an overview describing the strength and weakness of conventional and emerging technologies is provided. This review also updates the diverse cytogenetic abnormalities found in B-cell lymphomas, emphasizing their value in treatment decision...
May 15, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28479369/genomic-profiling-of-advanced-non-small-cell-lung-cancer-in-community-settings-gaps-and-opportunities
#18
Martin E Gutierrez, Kelly Choi, Richard B Lanman, Edward J Licitra, Stanley M Skrzypczak, Ruth Pe Benito, Tommy Wu, Srikesh Arunajadai, Sukhi Kaur, Harry Harper, Andrew L Pecora, Eric V Schultz, Stuart L Goldberg
BACKGROUND: National guidelines have advocated broad molecular profiling as a part of the standard diagnostic evaluation for advanced non-small cell lung cancer (NSCLC), with the goal of identifying driver mutations for which effective therapies or clinical trials are available. However, adherence to genomic testing guidelines could present challenges to community oncologists. PATIENTS AND METHODS: We performed a retrospective review of genomic testing patterns in patients with nonsquamous NSCLC treated by 89 oncologists at 15 sites throughout New Jersey and Maryland from January 2013 to December 2015...
April 13, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28465297/comprehensive-transcriptome-and-mutational-profiling-of-endemic-burkitt-lymphoma-reveals-ebv-type-specific-differences
#19
Yasin Kaymaz, Cliff I Oduor, Hongbo Yu, Juliana A Otieno, John Michael Ong'echa, Ann M Moormann, Jeffrey A Bailey
Endemic Burkitt lymphoma (eBL) is the most common pediatric cancer in malaria-endemic equatorial Africa and nearly always contains Epstein-Barr virus (EBV), unlike sporadic Burkitt lymphoma (sBL) that occurs with a lower incidence in developed countries. Given these differences and the variable clinical presentation and outcomes, we sought to further understand pathogenesis by investigating transcriptomes using RNA sequencing (RNAseq) from multiple primary eBL tumors compared with sBL tumors. Within eBL tumors, minimal expression differences were found based on: anatomical presentation site, in-hospital survival rates, and EBV genome type, suggesting that eBL tumors are homogeneous without marked subtypes...
May 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28454440/ffj-3-inhibits-pkm2-protein-expression-via-the-pi3k-akt-signaling-pathway-and-activates-the-mitochondrial-apoptosis-signaling-pathway-in-human-cancer-cells
#20
Dengyun Li, Xiaoli Wei, Mingming Ma, Huina Jia, Yu Zhang, Wenyi Kang, Tianxiao Wang, Xiaoyan Shi
Pyruvate kinase isoenzyme M2 (PKM2) has previously been identified as a tumor biomarker and potential therapeutic target for the treatment of cancer. In the present study, FFJ-3, a structurally modified version of mollugin, an extract of the Traditional Chinese herbal medicine Rubia tinctorum (madder) was used in order to determine the anticancer activity of the compound and investigate the potential mechanisms underlying this effect in human cancer cells. The results of the present study revealed that FFJ-3 inhibited the survival of HepG2 human hepatoma cells, MCF-7 human breast cancer cells and A549 human lung adenocarcinoma cells using the MTT assay...
April 2017: Oncology Letters
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